Structural basis for the interaction of antibiotics with peptidyl transferase center in eubacteria

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

Schlunzen, Frank; Zarivach, Raz; Harms, Jörg

2009-10-07

Ribosomes, the site of protein synthesis, are a major target for natural and synthetic antibiotics. Detailed knowledge of antibiotic binding sites is central to understanding the mechanisms of drug action. Conversely, drugs are excellent tools for studying the ribosome function. To elucidate the structural basis of ribosome-antibiotic interactions, we determined the high-resolution X-ray structures of the 50S ribosomal subunit of the eubacterium Deinococcus radiodurans, complexed with the clinically relevant antibiotics chloramphenicol, clindamycin and the three macrolides erythromycin, clarithromycin and roxithromycin. We found that antibiotic binding sites are composed exclusively of segments of 23S ribosomal RNA at the peptidyl transferase cavitymore » and do not involve any interaction of the drugs with ribosomal proteins. Here we report the details of antibiotic interactions with the components of their binding sites. Our results also show the importance of putative Mg{sup +2} ions for the binding of some drugs. This structural analysis should facilitate rational drug design.« less

Entering an era of dynamic structural biology….

PubMed

Orville, Allen M

2018-05-31

A recent paper in BMC Biology presents a general method for mix-and-inject serial crystallography, to facilitate the visualization of enzyme intermediates via time-resolved serial femtosecond crystallography (tr-SFX). They apply their method to resolve in near atomic detail the cleavage and inactivation of the antibiotic ceftriaxone by a β-lactamase enzyme from Mycobacterium tuberculosis. Their work demonstrates the general applicability of time-resolved crystallography, from which dynamic structures, at atomic resolution, can be obtained.See research article: https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-018-0524-5 .

Gating Topology of the Proton-Coupled Oligopeptide Symporters

PubMed Central

Fowler, Philip W.; Orwick-Rydmark, Marcella; Radestock, Sebastian; Solcan, Nicolae; Dijkman, Patricia M.; Lyons, Joseph A.; Kwok, Jane; Caffrey, Martin; Watts, Anthony; Forrest, Lucy R.; Newstead, Simon

2015-01-01

Summary Proton-coupled oligopeptide transporters belong to the major facilitator superfamily (MFS) of membrane transporters. Recent crystal structures suggest the MFS fold facilitates transport through rearrangement of their two six-helix bundles around a central ligand binding site; how this is achieved, however, is poorly understood. Using modeling, molecular dynamics, crystallography, functional assays, and site-directed spin labeling combined with double electron-electron resonance (DEER) spectroscopy, we present a detailed study of the transport dynamics of two bacterial oligopeptide transporters, PepTSo and PepTSt. Our results identify several salt bridges that stabilize outward-facing conformations and we show that, for all the current structures of MFS transporters, the first two helices of each of the four inverted-topology repeat units form half of either the periplasmic or cytoplasmic gate and that these function cooperatively in a scissor-like motion to control access to the peptide binding site during transport. PMID:25651061

Facilitative Components of Collaborative Learning: A Review of Nine Health Research Networks

PubMed Central

Rittner, Jessica Levin; Johnson, Karin E.; Gerteis, Jessie; Miller, Therese

2017-01-01

Objective: Collaborative research networks are increasingly used as an effective mechanism for accelerating knowledge transfer into policy and practice. This paper explored the characteristics and collaborative learning approaches of nine health research networks. Data sources/study setting: Semi-structured interviews with representatives from eight diverse US health services research networks conducted between November 2012 and January 2013 and program evaluation data from a ninth. Study design: The qualitative analysis assessed each network's purpose, duration, funding sources, governance structure, methods used to foster collaboration, and barriers and facilitators to collaborative learning. Data collection: The authors reviewed detailed notes from the interviews to distill salient themes. Principal findings: Face-to-face meetings, intentional facilitation and communication, shared vision, trust among members and willingness to work together were key facilitators of collaborative learning. Competing priorities for members, limited funding and lack of long-term support and geographic dispersion were the main barriers to coordination and collaboration across research network members. Conclusion: The findings illustrate the importance of collaborative learning in research networks and the challenges to evaluating the success of research network functionality. Conducting readiness assessments and developing process and outcome evaluation metrics will advance the design and show the impact of collaborative research networks. PMID:28277202

Facilitating the exploitation of ERTS imagery using snow enhancement techniques

NASA Technical Reports Server (NTRS)

Wobber, F. J. (Principal Investigator); Martin, K. R.; Amato, R. V.

1973-01-01

The author has identified the following significant results. New fracture detail within New England test area has been interpreted from ERTS-1 images. Comparative analysis of snow-free imagery (1096-15065 and 1096-15072) has demonstrated that MSS bands 5 and 7 supply the greatest amount of geological fracture detail. Interpretation of the first snow-covered ERTS-1 images (1132-15074 and 1168-15065) in correlation with ground snow depth data indicates that a heavy blanket of snow (less than 9 inches) accentuates major structural features while a light dusting (greater than 1 inch) accentuates more subtle topographic expressions. Snow cover was found to accentuate drainage patterns which are indicative of lithological and/or structural variations. Snow cover provided added enhancement for viewing and detecting topographically expressed fractures and faults. A recent field investigation was conducted within the New England test area to field check lineaments observed from analysis of ERTS-1 imagery, collect snow depth readings, and obtain structural joint readings at key locations in the test area.

The methodology of multi-viewpoint clustering analysis

NASA Technical Reports Server (NTRS)

Mehrotra, Mala; Wild, Chris

1993-01-01

One of the greatest challenges facing the software engineering community is the ability to produce large and complex computer systems, such as ground support systems for unmanned scientific missions, that are reliable and cost effective. In order to build and maintain these systems, it is important that the knowledge in the system be suitably abstracted, structured, and otherwise clustered in a manner which facilitates its understanding, manipulation, testing, and utilization. Development of complex mission-critical systems will require the ability to abstract overall concepts in the system at various levels of detail and to consider the system from different points of view. Multi-ViewPoint - Clustering Analysis MVP-CA methodology has been developed to provide multiple views of large, complicated systems. MVP-CA provides an ability to discover significant structures by providing an automated mechanism to structure both hierarchically (from detail to abstract) and orthogonally (from different perspectives). We propose to integrate MVP/CA into an overall software engineering life cycle to support the development and evolution of complex mission critical systems.

Threading the biophysics of mammalian Slo1 channels onto structures of an invertebrate Slo1 channel

PubMed Central

2017-01-01

For those interested in the machinery of ion channel gating, the Ca2+ and voltage-activated BK K+ channel provides a compelling topic for investigation, by virtue of its dual allosteric regulation by both voltage and intracellular Ca2+ and because its large-single channel conductance facilitates detailed kinetic analysis. Over the years, biophysical analyses have illuminated details of the allosteric regulation of BK channels and revealed insights into the mechanism of BK gating, e.g., inner cavity size and accessibility and voltage sensor-pore coupling. Now the publication of two structures of an Aplysia californica BK channel—one liganded and one metal free—promises to reinvigorate functional studies and interpretation of biophysical results. The new structures confirm some of the previous functional inferences but also suggest new perspectives regarding cooperativity between Ca2+-binding sites and the relationship between voltage- and Ca2+-dependent gating. Here we consider the extent to which the two structures explain previous functional data on pore-domain properties, voltage-sensor motions, and divalent cation binding and activation of the channel. PMID:29025867

A case study: the evolution of a "facilitator model" liaison program in an academic medical library.

PubMed

Crossno, Jon E; DeShay, Claudia H; Huslig, Mary Ann; Mayo, Helen G; Patridge, Emily F

2012-07-01

What type of liaison program would best utilize both librarians and other library staff to effectively promote library services and resources to campus departments? The case is an academic medical center library serving a large, diverse campus. The library implemented a "facilitator model" program to provide personalized service to targeted clients that allowed for maximum staff participation with limited subject familiarity. To determine success, details of liaison-contact interactions and results of liaison and department surveys were reviewed. Liaisons successfully recorded 595 interactions during the program's first 10 months of existence. A significant majority of departmental contact persons (82.5%) indicated they were aware of the liaison program, and 75% indicated they preferred email communication. The "facilitator model" provides a well-defined structure for assigning liaisons to departments or groups; however, training is essential to ensure that liaisons are able to communicate effectively with their clients.

Design of a Model Execution Framework: Repetitive Object-Oriented Simulation Environment (ROSE)

NASA Technical Reports Server (NTRS)

Gray, Justin S.; Briggs, Jeffery L.

2008-01-01

The ROSE framework was designed to facilitate complex system analyses. It completely divorces the model execution process from the model itself. By doing so ROSE frees the modeler to develop a library of standard modeling processes such as Design of Experiments, optimizers, parameter studies, and sensitivity studies which can then be applied to any of their available models. The ROSE framework accomplishes this by means of a well defined API and object structure. Both the API and object structure are presented here with enough detail to implement ROSE in any object-oriented language or modeling tool.

A combined histological and MRI brain atlas of the common marmoset monkey, Callithrix jacchus.

PubMed

Newman, John D; Kenkel, William M; Aronoff, Emily C; Bock, Nicholas A; Zametkin, Molly R; Silva, Afonso C

2009-12-11

The common marmoset, Callithrix jacchus, is of growing importance for research in neuroscience and related fields. In the present work, we describe a combined histological and magnetic resonance imaging (MRI) atlas constructed from the brains of two adult female marmosets. Histological sections were processed from Nissl staining and digitized to produce an atlas in a large format that facilitates visualization of structures with significant detail. Naming of identifiable brain structures was performed utilizing current terminology. The histological sections and a simplified schematic atlas are available online at http://udn.nichd.nih.gov/brainatlas_home.html.

Computer Simulation For Design Of TWT's

NASA Technical Reports Server (NTRS)

Bartos, Karen F.; Fite, E. Brian; Shalkhauser, Kurt A.; Sharp, G. Richard

1992-01-01

A three-dimensional finite-element analytical technique facilitates design and fabrication of traveling-wave-tube (TWT) slow-wave structures. Used to perform thermal and mechanical analyses of TWT designed with variety of configurations, geometries, and materials. Using three-dimensional computer analysis, designer able to simulate building and testing of TWT, with consequent substantial saving of time and money. Technique enables detailed look into operation of traveling-wave tubes to help improve performance for future communications systems.

Structure and mechanical implications of the pectoral fin skeleton in the Longnose Skate (Chondrichthyes, Batoidea).

PubMed

Huang, Wei; Hongjamrassilp, Watcharapong; Jung, Jae-Young; Hastings, Philip A; Lubarda, Vlado A; McKittrick, Joanna

2017-03-15

Animal propulsion systems are believed to show high energy and mechanical efficiency in assisting movement compared to artificial designs. As an example, batoid fishes have very light cartilaginous skeletons that facilitate their elegant swimming via enlarged wing-like pectoral fins. The aim of this work is to illustrate the hierarchical structure of the pectoral fin of a representative batoid, the Longnose Skate (Raja rhina), and explain the mechanical implications of its structural design. At the macro level, the pectoral fins are comprised of radially oriented fin rays, formed by staggered mineralized skeletal elements stacked end-to-end. At the micro level, the midsection of each radial element is composed of three mineralized components, which consist of discrete segments (tesserae) that are mineralized cartilage and embedded in unmineralized cartilage. The radial elements are wrapped with aligned, unmineralized collagen fibers. This is the first report of the detailed structure of the ray elements, including the observation of a 3-chain mineralized tesserae. Structural analyses demonstrate that this configuration enhances stiffness in multiple directions. A two-dimensional numerical model based on the morphological analysis demonstrated that the tessera structure helps distributing shear, tensile and compressive stress more ideally, which can better support both lift and thrust forces when swimming without losing flexibility. Batoid fishes have very light cartilaginous skeletons that facilitate their elegant swimming by applying their enlarged wing-like pectoral fins. Previous studies have shown structural features and mechanical properties of the mineralized cartilage skeleton in various batoid fishes. However, the details of the pectoral fin structure at different length scales, as well as the relationship between the mechanical properties and structural design remains unknown. The present work illustrates the hierarchical structure of the pectoral fin of the Longnose Skate (a representative batoid fish) and verifies the materials configuration and structural design increases the stiffness of fin skeleton without a loss in flexibility. These results have implications for the design of strong but flexible materials and bio-inspired autonomous underwater vehicles (AUVs). Copyright © 2017 Acta Materialia Inc. All rights reserved.

Structure, function, and engineering of enzymes in isoflavonoid biosynthesis.

PubMed

Wang, Xiaoqiang

2011-03-01

Isoflavonoids are a large group of plant natural products and play important roles in plant defense. They also possess valuable health-promoting activities with significant health benefits for animals and humans. The isoflavonoids are identified primarily in leguminous plants and are synthesized through the central phenylpropanoid pathway and the specific isoflavonoid branch pathways in legumes. Structural studies of some key enzymes in the central phenylpropanoid pathway shed light on the early stages of the (iso)flavonoid biosynthetic process. Significant impact has also been made on structural studies of enzymes in the isoflavonoid branch pathways. Structures of isoflavonoid-specific NADPH-dependent reductases revealed how the (iso)flavonoid backbones are modified by reduction reactions and how enzymes specifically recognize isoflavonoids and catalyze stereo-specific reductions. Structural studies of isoflavonoid methyltransferases and glycosyltransferases revealed how isoflavonoids are further decorated with methyl group and sugars in different methylation and glycosylation patterns that determine their bioactivities and functions. In combination with mutagenesis and biochemical studies, the detailed structural information of these enzymes provides a basis for understanding the complex biosynthetic process, enzyme catalytic mechanisms, and substrate specificities. Structure-based homology modeling facilitates the functional characterization of these large groups of biosynthetic enzymes and their homologs. Structure-based enzyme engineering is becoming a new strategy for synthesis of bioactive isoflavonoids and also facilitates plant metabolic engineering towards improvement of quality and production of crop plants.

Structural Analysis of Chemokine Receptor–Ligand Interactions

PubMed Central

2017-01-01

This review focuses on the construction and application of structural chemokine receptor models for the elucidation of molecular determinants of chemokine receptor modulation and the structure-based discovery and design of chemokine receptor ligands. A comparative analysis of ligand binding pockets in chemokine receptors is presented, including a detailed description of the CXCR4, CCR2, CCR5, CCR9, and US28 X-ray structures, and their implication for modeling molecular interactions of chemokine receptors with small-molecule ligands, peptide ligands, and large antibodies and chemokines. These studies demonstrate how the integration of new structural information on chemokine receptors with extensive structure–activity relationship and site-directed mutagenesis data facilitates the prediction of the structure of chemokine receptor–ligand complexes that have not been crystallized. Finally, a review of structure-based ligand discovery and design studies based on chemokine receptor crystal structures and homology models illustrates the possibilities and challenges to find novel ligands for chemokine receptors. PMID:28165741

Issues in reflection and debriefing: how nurse educators structure experiential activities.

PubMed

Brackenreg, Jenni

2004-12-01

Experiential learning is particularly useful in vocational education programs where theory needs to be linked to practice. Although experiential learning is often advocated in nursing education and the importance of debriefing and reflection is almost always espoused, the focus in the literature has tended to be on detailed descriptions of the action phase with little close analysis of how the reflective phase is facilitated. The Lewinian model described by Kolb [Experiential Learning. Experience as Source of Learning and Development, Prentice-Hall, New Jersey, 1984] and the structuring approach suggested by Thiagarajan [Experiential Learning Packages, Prentice-Hall, Englewood Cliffs, NJ, 1980] have been used as the theoretical context for an exploration of how nurse teachers describe their facilitation of the debriefing and reflective phases of experiential learning activities. Explication of the entire planned experiential learning experience is important for increasing the chances of the student being able to close the experiential learning loop. The more covert reflective phases for facilitating experiential learning are crucial and if neglected, or inexpertly and insensitively handled, may at best lead to poor learning outcomes or at worst lead to emotional damage and ;unfinished business' for the student. Interviews with eight experienced university educators elicited descriptions of how they constructed experiential activities with special reference to their descriptions of how the debriefing or reflective phases were structured.

Characterization of Isomeric Glycans by Reversed Phase Liquid Chromatography-Electronic Excitation Dissociation Tandem Mass Spectrometry

NASA Astrophysics Data System (ADS)

Tang, Yang; Wei, Juan; Costello, Catherine E.; Lin, Cheng

2018-04-01

The occurrence of numerous structural isomers in glycans from biological sources presents a severe challenge for structural glycomics. The subtle differences among isomeric structures demand analytical methods that can provide structural details while working efficiently with on-line glycan separation methods. Although liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a powerful tool for mixture analysis, the commonly utilized collision-induced dissociation (CID) method often does not generate a sufficient number of fragments at the MS2 level for comprehensive structural characterization. Here, we studied the electronic excitation dissociation (EED) behaviors of metal-adducted, permethylated glycans, and identified key spectral features that could facilitate both topology and linkage determinations. We developed an EED-based, nanoscale, reversed phase (RP)LC-MS/MS platform, and demonstrated its ability to achieve complete structural elucidation of up to five structural isomers in a single LC-MS/MS analysis. [Figure not available: see fulltext.

Do Gender-Specific and High-Resolution Three Dimensional Body Charts Facilitate the Communication of Pain for Women? A Quantitative and Qualitative Study

PubMed Central

Egsgaard, Line Lindhardt

2016-01-01

Background Chronic pain is more prevalent among women; however, the majority of standardized pain drawings are often collected using male-like androgynous body representations. Objective The purpose of this study was to assess whether gender-specific and high-resolution three-dimensional (3D) body charts facilitate the communication of pain for women. Methods Using mixed-methods and a cross-over design, female patients with chronic pain were asked to provide detailed drawings of their current pain on masculine and feminine two-dimensional (2D) body schemas (N=41, Part I) or on female 2D and 3D high-resolution body schemas (N=41, Part II) on a computer tablet. The consistency of the drawings between body charts were assessed by intraclass correlation coefficient (ICC) and Bland-Altman plots. Semistructured interviews and a preference questionnaire were then used to obtain qualitative and quantitative responses of the drawing experience. Results The consistency between body charts were high (Part I: ICC=0.980, Part II: ICC=0.994). The preference ratio for the masculine to feminine body schemas were 6:35 and 18:23 for the 2D to 3D female body charts. Patients reported that the 3D body chart enabled a more accurate expression of their pain due to the detailed contours of the musculature and bone structure, however, patients also reported the 3D body chart was too human and believed that skin-like appearance limited ‘deep pain’ expressions. Conclusions Providing gender-specific body charts may facilitate the communication of pain and the level of detail (2D vs 3D body charts) should be used according to patients’ needs. PMID:27440737

Anatomy of the Volar Retinacular Elements of the Hand: A Unified Nomenclature.

PubMed

Godfrey, Jenna; Rayan, Ghazi M

2018-03-01

Many investigators have described the anatomy of the volar retinacular structures of the hand over the last 60 years. As a result, multiple terms have been assigned to 1 anatomical structure and 1 name designated to more than 1 structure. Our purpose is to review the detailed anatomy and key components of the volar retinacular elements of the hand, their etymology, and their most recent descriptions. The objective also is to organize these structures into systems, which can be helpful for learners to assimilate into a practical anatomical guide. Lastly, the goal is to create a common nomenclature for identifying the volar retinacular structures of the hand in order to facilitate clear communication about them across languages. Copyright © 2018 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

RipleyGUI: software for analyzing spatial patterns in 3D cell distributions

PubMed Central

Hansson, Kristin; Jafari-Mamaghani, Mehrdad; Krieger, Patrik

2013-01-01

The true revolution in the age of digital neuroanatomy is the ability to extensively quantify anatomical structures and thus investigate structure-function relationships in great detail. To facilitate the quantification of neuronal cell patterns we have developed RipleyGUI, a MATLAB-based software that can be used to detect patterns in the 3D distribution of cells. RipleyGUI uses Ripley's K-function to analyze spatial distributions. In addition the software contains statistical tools to determine quantitative statistical differences, and tools for spatial transformations that are useful for analyzing non-stationary point patterns. The software has a graphical user interface making it easy to use without programming experience, and an extensive user manual explaining the basic concepts underlying the different statistical tools used to analyze spatial point patterns. The described analysis tool can be used for determining the spatial organization of neurons that is important for a detailed study of structure-function relationships. For example, neocortex that can be subdivided into six layers based on cell density and cell types can also be analyzed in terms of organizational principles distinguishing the layers. PMID:23658544

Implementing an effective organization and governance structure for a radiology practice.

PubMed

Muroff, Lawrence R

2004-01-01

Radiology practices that are well organized and effectively governed have a competitive advantage. Decisions are made rapidly, actions are taken decisively and in accordance with established policy, and each group member has a responsibility for practice building. Such groups are perceived by their peers, hospital administration, and community business leaders to be both formidable and effective. This paper details the mechanisms that facilitate planning for and implementing an efficient practice organization and governance structure. The tasks of group leaders are defined, as are the committees necessary for appropriate action. The integral roles of a mission statement and a business plan are discussed. Practices adopting the suggested organizational structure will be best positioned to survive in both good times and bad.

Simulation of a navigator algorithm for a low-cost GPS receiver

NASA Technical Reports Server (NTRS)

Hodge, W. F.

1980-01-01

The analytical structure of an existing navigator algorithm for a low cost global positioning system receiver is described in detail to facilitate its implementation on in-house digital computers and real-time simulators. The material presented includes a simulation of GPS pseudorange measurements, based on a two-body representation of the NAVSTAR spacecraft orbits, and a four component model of the receiver bias errors. A simpler test for loss of pseudorange measurements due to spacecraft shielding is also noted.

Vulnerability-attention analysis for space-related activities

NASA Technical Reports Server (NTRS)

Ford, Donnie; Hays, Dan; Lee, Sung Yong; Wolfsberger, John

1988-01-01

Techniques for representing and analyzing trouble spots in structures and processes are discussed. Identification of vulnerable areas usually depends more on particular and often detailed knowledge than on algorithmic or mathematical procedures. In some cases, machine inference can facilitate the identification. The analysis scheme proposed first establishes the geometry of the process, then marks areas that are conditionally vulnerable. This provides a basis for advice on the kinds of human attention or machine sensing and control that can make the risks tolerable.

Structural barriers and facilitators in HIV prevention: a review of international research.

PubMed

Parker, R G; Easton, D; Klein, C H

2000-06-01

This article provides an overview of a growing body of international research focusing on the structural and environmental factors that shape the spread of the HIV/AIDS epidemic, and create barriers and facilitators in relation to HIV-prevention programs. OVERVIEW OF STRUCTURAL-FACTORS LITERATURE: Most of the research on structural and environmental factors can be grouped into a small number of analytically distinct but interconnected categories: economic (under)development and poverty; mobility, including migration, seasonal work, and social disruption due to war and political instability; and gender inequalities. An additional focus in research on structural and environmental factors has been on the effects of particular governmental and intergovernmental policies in increasing or diminishing HIV vulnerability and transmission. A smaller subset of the research on structural factors describes and/or evaluates specific interventions in detail. Approaches that have received significant attention include targeted interventions developed for heterosexual women, female commercial sex workers, male truck drivers, and men who have sex with men. The structural and environmental factors literature offers important insights and reveals a number of productive intervention strategies that might be explored in both resource-rich and -poor settings. However, new methodologies are required to document and evaluate the effects of the structural interventions, which by their very nature involve large-scale elements that cannot be easily controlled by experimental or quasi-experimental research designs. Innovative, interdisciplinary approaches are needed that can move beyond the limited successes of traditional behavioral interventions and explicitly attempt to achieve broader social and structural change.

A case study: the evolution of a “facilitator model” liaison program in an academic medical library*

PubMed Central

DeShay, Claudia H.; Huslig, Mary Ann; Mayo, Helen G.; Patridge, Emily F.

2012-01-01

Question: What type of liaison program would best utilize both librarians and other library staff to effectively promote library services and resources to campus departments? Setting: The case is an academic medical center library serving a large, diverse campus. Methods: The library implemented a “facilitator model” program to provide personalized service to targeted clients that allowed for maximum staff participation with limited subject familiarity. To determine success, details of liaison-contact interactions and results of liaison and department surveys were reviewed. Results: Liaisons successfully recorded 595 interactions during the program's first 10 months of existence. A significant majority of departmental contact persons (82.5%) indicated they were aware of the liaison program, and 75% indicated they preferred email communication. Conclusion: The “facilitator model” provides a well-defined structure for assigning liaisons to departments or groups; however, training is essential to ensure that liaisons are able to communicate effectively with their clients. PMID:22879805

What Children Recall about a Repeated Event When One Instance Is Different from the Others

ERIC Educational Resources Information Center

Connolly, Deborah A.; Gordon, Heidi M.; Woiwod, Dayna M.; Price, Heather L.

2016-01-01

This research examined whether a memorable and unexpected change (deviation details) presented during 1 instance of a repeated event facilitated children's memory for that instance and whether a repeated event facilitated children's memory for deviation details. In Experiments 1 and 2, 8-year-olds (N = 167) watched 1 or 4 live magic shows.…

Optimal charges in lead progression: a structure-based neuraminidase case study.

PubMed

Armstrong, Kathryn A; Tidor, Bruce; Cheng, Alan C

2006-04-20

Collective experience in structure-based lead progression has found electrostatic interactions to be more difficult to optimize than shape-based ones. A major reason for this is that the net electrostatic contribution observed includes a significant nonintuitive desolvation component in addition to the more intuitive intermolecular interaction component. To investigate whether knowledge of the ligand optimal charge distribution can facilitate more intuitive design of electrostatic interactions, we took a series of small-molecule influenza neuraminidase inhibitors with known protein cocrystal structures and calculated the difference between the optimal and actual charge distributions. This difference from the electrostatic optimum correlates with the calculated electrostatic contribution to binding (r(2) = 0.94) despite small changes in binding modes caused by chemical substitutions, suggesting that the optimal charge distribution is a useful design goal. Furthermore, detailed suggestions for chemical modification generated by this approach are in many cases consistent with observed improvements in binding affinity, and the method appears to be useful despite discrete chemical constraints. Taken together, these results suggest that charge optimization is useful in facilitating generation of compound ideas in lead optimization. Our results also provide insight into design of neuraminidase inhibitors.

Subnanometre-resolution structure of the doublet microtubule reveals new classes of microtubule-associated proteins

PubMed Central

Ichikawa, Muneyoshi; Liu, Dinan; Kastritis, Panagiotis L.; Basu, Kaustuv; Hsu, Tzu Chin; Yang, Shunkai; Bui, Khanh Huy

2017-01-01

Cilia are ubiquitous, hair-like appendages found in eukaryotic cells that carry out functions of cell motility and sensory reception. Cilia contain an intriguing cytoskeletal structure, termed the axoneme that consists of nine doublet microtubules radially interlinked and longitudinally organized in multiple specific repeat units. Little is known, however, about how the axoneme allows cilia to be both actively bendable and sturdy or how it is assembled. To answer these questions, we used cryo-electron microscopy to structurally analyse several of the repeating units of the doublet at sub-nanometre resolution. This structural detail enables us to unambiguously assign α- and β-tubulins in the doublet microtubule lattice. Our study demonstrates the existence of an inner sheath composed of different kinds of microtubule inner proteins inside the doublet that likely stabilizes the structure and facilitates the specific building of the B-tubule. PMID:28462916

The Turn the Tables Technique (T[cube]): A Program Activity to Provide Group Facilitators Insight into Teen Sexual Behaviors and Beliefs

ERIC Educational Resources Information Center

Sclafane, Jamie Heather; Merves, Marni Loiacono; Rivera, Angelic; Long, Laura; Wilson, Ken; Bauman, Laurie J.

2012-01-01

The Turn the Tables Technique (T[cube]) is an activity designed to provide group facilitators who lead HIV/STI prevention and sexual health promotion programs with detailed and current information on teenagers' sexual behaviors and beliefs. This information can be used throughout a program to tailor content. Included is a detailed lesson plan of…

Investigation of hindwing folding in ladybird beetles by artificial elytron transplantation and microcomputed tomography.

PubMed

Saito, Kazuya; Nomura, Shuhei; Yamamoto, Shuhei; Niiyama, Ryuma; Okabe, Yoji

2017-05-30

Ladybird beetles are high-mobility insects and explore broad areas by switching between walking and flying. Their excellent wing transformation systems enabling this lifestyle are expected to provide large potential for engineering applications. However, the mechanism behind the folding of their hindwings remains unclear. The reason is that ladybird beetles close the elytra ahead of wing folding, preventing the observation of detailed processes occurring under the elytra. In the present study, artificial transparent elytra were transplanted on living ladybird beetles, thereby enabling us to observe the detailed wing-folding processes. The result revealed that in addition to the abdominal movements mentioned in previous studies, the edge and ventral surface of the elytra, as well as characteristic shaped veins, play important roles in wing folding. The structures of the wing frames enabling this folding process and detailed 3D shape of the hindwing were investigated using microcomputed tomography. The results showed that the tape spring-like elastic frame plays an important role in the wing transformation mechanism. Compared with other beetles, hindwings in ladybird beetles are characterized by two seemingly incompatible properties: ( i ) the wing rigidity with relatively thick veins and ( ii ) the compactness in stored shapes with complex crease patterns. The detailed wing-folding process revealed in this study is expected to facilitate understanding of the naturally optimized system in this excellent deployable structure.

Investigation of hindwing folding in ladybird beetles by artificial elytron transplantation and microcomputed tomography

PubMed Central

Nomura, Shuhei; Yamamoto, Shuhei; Niiyama, Ryuma; Okabe, Yoji

2017-01-01

Ladybird beetles are high-mobility insects and explore broad areas by switching between walking and flying. Their excellent wing transformation systems enabling this lifestyle are expected to provide large potential for engineering applications. However, the mechanism behind the folding of their hindwings remains unclear. The reason is that ladybird beetles close the elytra ahead of wing folding, preventing the observation of detailed processes occurring under the elytra. In the present study, artificial transparent elytra were transplanted on living ladybird beetles, thereby enabling us to observe the detailed wing-folding processes. The result revealed that in addition to the abdominal movements mentioned in previous studies, the edge and ventral surface of the elytra, as well as characteristic shaped veins, play important roles in wing folding. The structures of the wing frames enabling this folding process and detailed 3D shape of the hindwing were investigated using microcomputed tomography. The results showed that the tape spring-like elastic frame plays an important role in the wing transformation mechanism. Compared with other beetles, hindwings in ladybird beetles are characterized by two seemingly incompatible properties: (i) the wing rigidity with relatively thick veins and (ii) the compactness in stored shapes with complex crease patterns. The detailed wing-folding process revealed in this study is expected to facilitate understanding of the naturally optimized system in this excellent deployable structure. PMID:28507159

NALDB: nucleic acid ligand database for small molecules targeting nucleic acid

PubMed Central

Kumar Mishra, Subodh; Kumar, Amit

2016-01-01

Nucleic acid ligand database (NALDB) is a unique database that provides detailed information about the experimental data of small molecules that were reported to target several types of nucleic acid structures. NALDB is the first ligand database that contains ligand information for all type of nucleic acid. NALDB contains more than 3500 ligand entries with detailed pharmacokinetic and pharmacodynamic information such as target name, target sequence, ligand 2D/3D structure, SMILES, molecular formula, molecular weight, net-formal charge, AlogP, number of rings, number of hydrogen bond donor and acceptor, potential energy along with their Ki, Kd, IC50 values. All these details at single platform would be helpful for the development and betterment of novel ligands targeting nucleic acids that could serve as a potential target in different diseases including cancers and neurological disorders. With maximum 255 conformers for each ligand entry, our database is a multi-conformer database and can facilitate the virtual screening process. NALDB provides powerful web-based search tools that make database searching efficient and simplified using option for text as well as for structure query. NALDB also provides multi-dimensional advanced search tool which can screen the database molecules on the basis of molecular properties of ligand provided by database users. A 3D structure visualization tool has also been included for 3D structure representation of ligands. NALDB offers an inclusive pharmacological information and the structurally flexible set of small molecules with their three-dimensional conformers that can accelerate the virtual screening and other modeling processes and eventually complement the nucleic acid-based drug discovery research. NALDB can be routinely updated and freely available on bsbe.iiti.ac.in/bsbe/naldb/HOME.php. Database URL: http://bsbe.iiti.ac.in/bsbe/naldb/HOME.php PMID:26896846

Structures of ribonucleoprotein particle modification enzymes

PubMed Central

Liang, Bo; Li, Hong

2016-01-01

Small nucleolar and Cajal body ribonucleoprotein particles (RNPs) are required for the maturation of ribosomes and spliceosomes. They consist of small nucleolar RNA or Cajal body RNA combined with partner proteins and represent the most complex RNA modification enzymes. Recent advances in structure and function studies have revealed detailed information regarding ribonucleoprotein assembly and substrate binding. These enzymes form intertwined RNA–protein assemblies that facilitate reversible binding of the large ribosomal RNA or small nuclear RNA. These revelations explain the specificity among the components in enzyme assembly and substrate modification. The multiple conformations of individual components and those of complete RNPs suggest a dynamic assembly process and justify the requirement of many assembly factors in vivo. PMID:21108865

Consumables data base workbook: Formulation of consumables management models

NASA Technical Reports Server (NTRS)

Zamora, M. A.

1977-01-01

Activity consumables data specifications and data applications are presented. The data are structured in a series of "Consumable Data Worksheets" for each activity that includes a profile of its operations and the rate of each consumable required to support the given activity. The data worksheets provide for the uniform specification of consumables data, allows for the ready identification of the consumables affected by a given activity, and facilitates the updating process. An activity is defined and the data that must be included in the data worksheets are specified. An example of its use and application is given, i.e. consumables data requirements for the performance of the EVA. The consumables data for the activities currently identified for the shuttle spacecraft are included. The consumables data sources are identified and information to facilitate the maintenance process is detailed.

Can we infer plant facilitation from remote sensing? A test across global drylands

PubMed Central

Xu, Chi; Holmgren, Milena; Van Nes, Egbert H.; Maestre, Fernando T.; Soliveres, Santiago; Berdugo, Miguel; Kéfi, Sonia; Marquet, Pablo A.; Abades, Sebastian; Scheffer, Marten

2016-01-01

Facilitation is a major force shaping the structure and diversity of plant communities in terrestrial ecosystems. Detecting positive plant-plant interactions relies on the combination of field experimentation and the demonstration of spatial association between neighboring plants. This has often restricted the study of facilitation to particular sites, limiting the development of systematic assessments of facilitation over regional and global scales. Here we explore whether the frequency of plant spatial associations detected from high-resolution remotely-sensed images can be used to infer plant facilitation at the community level in drylands around the globe. We correlated the information from remotely-sensed images freely available through Google Earth™ with detailed field assessments, and used a simple individual-based model to generate patch-size distributions using different assumptions about the type and strength of plant-plant interactions. Most of the patterns found from the remotely-sensed images were more right-skewed than the patterns from the null model simulating a random distribution. This suggests that the plants in the studied drylands show stronger spatial clustering than expected by chance. We found that positive plant co-occurrence, as measured in the field, was significantly related to the skewness of vegetation patch-size distribution measured using Google Earth™ images. Our findings suggest that the relative frequency of facilitation may be inferred from spatial pattern signals measured from remotely-sensed images, since facilitation often determines positive co-occurrence among neighboring plants. They pave the road for a systematic global assessment of the role of facilitation in terrestrial ecosystems. PMID:26552256

IPUMS: Detailed global data on population characteristics

NASA Astrophysics Data System (ADS)

Kugler, T.

2017-12-01

Many new and exciting sources of data on human population distributions based on remote sensing, mobile technology, and other mechanisms are becoming available. These new data sources often provide fine scale spatial and/or temporal resolution. However, they typically focus on the location of population, with little or no information on population characteristics. The large and growing collection of data available through the IPUMS family of products complements datasets that provide spatial and temporal detail but little attribute detail by providing the full depth of characteristics covered by population censuses, including demographic, household structure, economic, employment, education, and housing characteristics. IPUMS International provides census microdata for 85 countries. Microdata provide the responses to every census question for each individual in a sample of households. Microdata identify the sub-national geographic unit in which a household is located, but for confidentiality reasons, identified units must include a minimum population, typically 20,000 people. Small-area aggregate data often describe much smaller geographic units, enabling study of detailed spatial patterns of population characteristics. However the structure of aggregate data tables is highly heterogeneous across countries, census years, and even topics within a given census, making these data difficult to work with in any systematic way. A recently funded project will assemble small-area aggregate population and agricultural census data published by national statistical offices. Through preliminary work collecting and cataloging over 10,000 tables, we have identified a small number of structural families that can be used to organize the many different structures. These structural families will form the basis for software tools to document and standardize the tables for ingest into a common database. Both the microdata and aggregate data are made available through IPUMS Terra, facilitating integration with land use, land cover, climate, and other environmental data. These data can be used to address pressing global challenges, such as food and water security, development and deforestation, and environmentally-influenced migration.

High-speed atomic force microscopy coming of age

NASA Astrophysics Data System (ADS)

Ando, Toshio

2012-02-01

High-speed atomic force microscopy (HS-AFM) is now materialized. It allows direct visualization of dynamic structural changes and dynamic processes of functioning biological molecules in physiological solutions, at high spatiotemporal resolution. Dynamic molecular events unselectively appear in detail in an AFM movie, facilitating our understanding of how biological molecules operate to function. This review describes a historical overview of technical development towards HS-AFM, summarizes elementary devices and techniques used in the current HS-AFM, and then highlights recent imaging studies. Finally, future challenges of HS-AFM studies are briefly discussed.

Nine steps towards a better water meter management.

PubMed

Arregui, F J; Soriano, J; Cabrera, E; Cobacho, R

2012-01-01

The paper provides a comprehensive perspective of the critical aspects to be taken into account when planning the long-term management of water meters in a utility. In order to facilitate their quick understanding and practical implementation, they have been structured into nine steps. Ranging from an initial audit up to the final periodic meter replacement planning, these steps cover three aspects of the problem - field work, laboratory work and management tasks; and each one is developed in detail paying attention to the particular data needed and noting the practical outcome it will yield.

System software for the finite element machine

NASA Technical Reports Server (NTRS)

Crockett, T. W.; Knott, J. D.

1985-01-01

The Finite Element Machine is an experimental parallel computer developed at Langley Research Center to investigate the application of concurrent processing to structural engineering analysis. This report describes system-level software which has been developed to facilitate use of the machine by applications researchers. The overall software design is outlined, and several important parallel processing issues are discussed in detail, including processor management, communication, synchronization, and input/output. Based on experience using the system, the hardware architecture and software design are critiqued, and areas for further work are suggested.

PDDL4J: a planning domain description library for java

NASA Astrophysics Data System (ADS)

Pellier, D.; Fiorino, H.

2018-01-01

PDDL4J (Planning Domain Description Library for Java) is an open source toolkit for Java cross-platform developers meant (1) to provide state-of-the-art planners based on the Pddl language, and (2) to facilitate research works on new planners. In this article, we present an overview of the Automated Planning concepts and languages. We present some planning systems and their most significant applications. Then, we detail the Pddl4j toolkit with an emphasis on the available informative structures, heuristics and search algorithms.

Hierarchical, Three-Dimensional Measurement System for Crime Scene Scanning.

PubMed

Marcin, Adamczyk; Maciej, Sieniło; Robert, Sitnik; Adam, Woźniak

2017-07-01

We present a new generation of three-dimensional (3D) measuring systems, developed for the process of crime scene documentation. This measuring system facilitates the preparation of more insightful, complete, and objective documentation for crime scenes. Our system reflects the actual requirements for hierarchical documentation, and it consists of three independent 3D scanners: a laser scanner for overall measurements, a situational structured light scanner for more minute measurements, and a detailed structured light scanner for the most detailed parts of tscene. Each scanner has its own spatial resolution, of 2.0, 0.3, and 0.05 mm, respectively. The results of interviews we have conducted with technicians indicate that our developed 3D measuring system has significant potential to become a useful tool for forensic technicians. To ensure the maximum compatibility of our measuring system with the standards that regulate the documentation process, we have also performed a metrological validation and designated the maximum permissible length measurement error E MPE for each structured light scanner. In this study, we present additional results regarding documentation processes conducted during crime scene inspections and a training session. © 2017 American Academy of Forensic Sciences.

Structurally detailed coarse-grained model for Sec-facilitated co-translational protein translocation and membrane integration

PubMed Central

Miller, Thomas F.

2017-01-01

We present a coarse-grained simulation model that is capable of simulating the minute-timescale dynamics of protein translocation and membrane integration via the Sec translocon, while retaining sufficient chemical and structural detail to capture many of the sequence-specific interactions that drive these processes. The model includes accurate geometric representations of the ribosome and Sec translocon, obtained directly from experimental structures, and interactions parameterized from nearly 200 μs of residue-based coarse-grained molecular dynamics simulations. A protocol for mapping amino-acid sequences to coarse-grained beads enables the direct simulation of trajectories for the co-translational insertion of arbitrary polypeptide sequences into the Sec translocon. The model reproduces experimentally observed features of membrane protein integration, including the efficiency with which polypeptide domains integrate into the membrane, the variation in integration efficiency upon single amino-acid mutations, and the orientation of transmembrane domains. The central advantage of the model is that it connects sequence-level protein features to biological observables and timescales, enabling direct simulation for the mechanistic analysis of co-translational integration and for the engineering of membrane proteins with enhanced membrane integration efficiency. PMID:28328943

Detailed Design Documentation, without the Pain

NASA Astrophysics Data System (ADS)

Ramsay, C. D.; Parkes, S.

2004-06-01

Producing detailed forms of design documentation, such as pseudocode and structured flowcharts, to describe the procedures of a software system:(1) allows software developers to model and discuss their understanding of a problem and the design of a solution free from the syntax of a programming language,(2) facilitates deeper involvement of non-technical stakeholders, such as the customer or project managers, whose influence ensures the quality, correctness and timeliness of the resulting system,(3) forms comprehensive documentation of the system for its future maintenance, reuse and/or redeployment.However, such forms of documentation require effort to create and maintain.This paper describes a software tool which is currently being developed within the Space Systems Research Group at the University of Dundee which aims to improve the utility of, and the incentive for, creating detailed design documentation for the procedures of a software system. The rationale for creating such a tool is briefly discussed, followed by a description of the tool itself, a summary of its perceived benefits, and plans for future work.

Designing strategies and tools for teacher training: The role of critical details, examples in optics

NASA Astrophysics Data System (ADS)

Viennot, Laurence; Chauvet, Françoise; Colin, Philippe; Rebmann, Gérard

2005-01-01

Within the overall STTIS (Science Teacher Training in an Information Society) framework, this paper focuses on transformations of innovative teaching of optics, following a recommended change of approach to optics in the French curriculum. The empirical investigation of how teachers responded to this change, the main results of which are briefly presented here, identified a crucial aspect of the problem. This is the importance of critical detail'': that is, the fact that the linkage between certain critical details of practice and the fundamental rationale of a teaching sequence is often not easily understood by teachers, even those who are strongly motivated. The paper then discusses the development of guidelines for the design of training materials based on these research findings, which show how teachers typically tend to transform innovations when putting them into practice. We describe the rationale behind and structure of some teacher training materials intended to facilitate awareness and mastery in this respect.

Revealing the synergetic effects in Ni nanoparticle-carbon nanotube hybrids by scanning transmission X-ray microscopy and their application in the hydrolysis of ammonia borane

NASA Astrophysics Data System (ADS)

Zhao, Guanqi; Zhong, Jun; Wang, Jian; Sham, Tsun-Kong; Sun, Xuhui; Lee, Shuit-Tong

2015-05-01

The hybrids of carbon nanotubes (CNTs) and the supported Ni nanoparticles (NPs) have been studied by scanning transmission X-ray microscopy (STXM) and tested by the hydrolysis reaction of ammonia borane (AB, NH3BH3). Data clearly showed the existence of a strong interaction between Ni NPs and thin CNTs (C-O-Ni bonds), which favored the tunable (buffer) electronic structure of Ni NPs facilitating the catalytic process. The hydrolysis process of AB confirmed the hypothesis that the hybrids with a strong interfacial interaction would show superior catalytic performance, while the hybrids with a weak interfacial interaction show poor performance. Our results provide a wealth of detailed information regarding the electronic structure of the NP-CNT hybrids and provide guidance towards the rational design of high-performance catalysts for energy applications.The hybrids of carbon nanotubes (CNTs) and the supported Ni nanoparticles (NPs) have been studied by scanning transmission X-ray microscopy (STXM) and tested by the hydrolysis reaction of ammonia borane (AB, NH3BH3). Data clearly showed the existence of a strong interaction between Ni NPs and thin CNTs (C-O-Ni bonds), which favored the tunable (buffer) electronic structure of Ni NPs facilitating the catalytic process. The hydrolysis process of AB confirmed the hypothesis that the hybrids with a strong interfacial interaction would show superior catalytic performance, while the hybrids with a weak interfacial interaction show poor performance. Our results provide a wealth of detailed information regarding the electronic structure of the NP-CNT hybrids and provide guidance towards the rational design of high-performance catalysts for energy applications. Electronic supplementary information (ESI) available: Magnified TEM images, high resolution TEM images and the particle size distributions of the samples, the STXM results of a thick tube at different positions, XPS results, stability test. See DOI: 10.1039/c5nr01168j

Development of a truss joint for robotic assembly of space structures

NASA Technical Reports Server (NTRS)

Parma, George F.

1992-01-01

This report presents the results of a detailed study of mechanical fasteners which were designed to facilitate robotic assembly of structures. Design requirements for robotic structural assembly were developed, taking into account structural properties and overall system design, and four candidate fasteners were designed to meet them. These fasteners were built and evaluated in the laboratory, and the Hammer-Head joint was chosen as superior overall. It had a high reliability of fastening under misalignments of 2.54 mm (0.1 in) and 3 deg, the highest end fixity (2.18), the simplest end effector, an integral capture guide, good visual verification, and the lightest weight (782 g, 1.72 lb). The study found that a good design should incorporate chamfers sliding on chamfers, cylinders sliding on chamfers, and hard surface finishes on sliding surfaces. The study also comments on robot flexibility, sag, hysteresis, thermal expansion, and friction which were observed during the testing.

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

Janjusic, Tommy; Kartsaklis, Christos

Application analysis is facilitated through a number of program profiling tools. The tools vary in their complexity, ease of deployment, design, and profiling detail. Specifically, understand- ing, analyzing, and optimizing is of particular importance for scientific applications where minor changes in code paths and data-structure layout can have profound effects. Understanding how intricate data-structures are accessed and how a given memory system responds is a complex task. In this paper we describe a trace profiling tool, Glprof, specifically aimed to lessen the burden of the programmer to pin-point heavily involved data-structures during an application's run-time, and understand data-structure run-time usage.more » Moreover, we showcase the tool's modularity using additional cache simulation components. We elaborate on the tool's design, and features. Finally we demonstrate the application of our tool in the context of Spec bench- marks using the Glprof profiler and two concurrently running cache simulators, PPC440 and AMD Interlagos.« less

Atomic resolution structure of the E. coli YajR transporter YAM domain.

PubMed

Jiang, Daohua; Zhao, Yan; Fan, Junping; Liu, Xuehui; Wu, Yan; Feng, Wei; Zhang, Xuejun C

2014-07-25

YajR is an Escherichia coli transporter that belongs to the major facilitator superfamily. Unlike most MFS transporters, YajR contains a carboxyl terminal, cytosolic domain of 67 amino acid residues termed YAM domain. Although it is speculated that the function of this small soluble domain is to regulate the conformational change of the 12-helix transmembrane domain, its precise regulatory role remains unclear. Here, we report the crystal structure of the YAM domain at 1.07-Å resolution, along with its structure determined using nuclear magnetic resonance. Detailed analysis of the high resolution structure revealed a symmetrical dimer in which a belt of well-ordered poly-pentagonal water molecules is embedded. A mutagenesis experiment and a thermal stability assay were used to analyze the putative role of this dimerization in response to changes in halogen concentration. Copyright © 2014 Elsevier Inc. All rights reserved.

The FapF amyloid secretion transporter possesses an atypical asymmetric coiled coil.

PubMed

Rouse, Sarah L; Stylianou, Fisentzos; Grace Wu, H Y; Berry, Jamie-Lee; Sewell, Lee; Morgan, R Marc L; Sauerwein, Andrea C; Matthews, Steve

2018-06-07

Gram-negative bacteria possess specialised biogenesis machineries that facilitate the export of amyloid subunits, the fibres of which are key components of their biofilm matrix. The secretion of bacterial functional amyloid requires a specialised outer-membrane protein channel through which unfolded amyloid substrates are translocated. We previously reported the crystal structure of the membrane-spanning domain of the amyloid subunit transporter FapF from Pseudomonas. However, the structure of the periplasmic domain, which is essential for amyloid transport, is yet to be determined. Here, we present the crystal structure of the N-terminal periplasmic domain at 1.8 Å resolution. This domain forms a novel asymmetric trimeric coiled-coil that possesses a single buried tyrosine residue as well as a extensive hydrogen-bonding network within a glutamine layer. This new structural insight allows us to understand this newly described functional amyloid secretion system in greater detail. Copyright © 2018. Published by Elsevier Ltd.

Arguments, contradictions, resistances, and conceptual change in students' understanding of atomic structure

NASA Astrophysics Data System (ADS)

Niaz, Mansoor; Aguilera, Damarys; Maza, Arelys; Liendo, Gustavo

2002-07-01

Most general chemistry courses and textbooks emphasize experimental details and lack a history and philosophy of science perspective. The objective of this study is to facilitate freshman general chemistry students' understanding of atomic structure based on the work of Thomson, Rutherford, and Bohr. It is hypothesized that classroom discussions based on arguments/counterarguments of the heuristic principles, on which these scientists based their atomic models, can facilitate students' conceptual understanding. This study is based on 160 freshman students enrolled in six sections of General Chemistry I (three sections formed part of the experimental group). All three models (Thomson, Rutherford, and Bohr) were presented to the experimental and control group students in the traditional manner, as found in most textbooks. After this, the three sections of the experimental group participated in the discussion of six items with alternative responses. Students were first asked to select a response and then participate in classroom discussions leading to arguments in favor or against the selected response and finally select a new response. Three weeks after having discussed the six items, both the experimental and control groups presented a monthly exam (based on the three models) and after another 3 weeks a semester exam. Results obtained show that given the opportunity to argue and discuss, students' understanding can go beyond the simple regurgitation of experimental details. Performance of the experimental group showed contradictions, resistances, and progressive conceptual change with considerable and consistent improvement in the last item. It is concluded that if we want our students to understand scientific progress and practice, then it is important that we include the experimental details not as a rhetoric of conclusions (Schwab, 1962, The teaching of science as enquiry, Cambridge, MA, Harward University Press; Schwab, 1974, Conflicting conceptions of curriculum, Berkeley, CA, McCutchan) but as heuristic principles (Lakatos, 1970, Criticism and the growth of knowledge, Cambridge, UK, Cambridge University Press, pp. 91-195), which were based on arguments, controversies, and interpretations of the scientists.

Thermophysical properties of U 3 Si 2 to 1773K

DOE PAGES

White, Joshua Taylor; Nelson, Andrew Thomas; Dunwoody, John Tyler; ...

2015-05-08

Use of U 3Si 2 in nuclear reactors requires accurate thermophysical property data to capture heat transfer within the core. Compilation of the limited previous research efforts focused on the most critical property, thermal conductivity, reveals extensive disagreement. Assessment of this data is challenged by the fact that the critical structural and chemical details of the material used to provide historic data is either absent or confirms the presence of significant impurity phases. This study was initiated to fabricate high purity U 3Si 2 to quantify the coefficient of thermal expansion, heat capacity, thermal diffusivity, and thermal conductivity from roommore » temperature to 1773 K. Here, the datasets provided in this manuscript will facilitate more detailed fuel performance modeling to assess both current and proposed reactor designs that incorporate U 3Si 2.« less

Functional phosphoproteomic mass spectrometry-based approaches

PubMed Central

2012-01-01

Mass Spectrometry (MS)-based phosphoproteomics tools are crucial for understanding the structure and dynamics of signaling networks. Approaches such as affinity purification followed by MS have also been used to elucidate relevant biological questions in health and disease. The study of proteomes and phosphoproteomes as linked systems, rather than research studies of individual proteins, are necessary to understand the functions of phosphorylated and un-phosphorylated proteins under spatial and temporal conditions. Phosphoproteome studies also facilitate drug target protein identification which may be clinically useful in the near future. Here, we provide an overview of general principles of signaling pathways versus phosphorylation. Likewise, we detail chemical phosphoproteomic tools, including pros and cons with examples where these methods have been applied. In addition, basic clues of electrospray ionization and collision induced dissociation fragmentation are detailed in a simple manner for successful phosphoproteomic clinical studies. PMID:23369623

Fluorescence probing of T box antiterminator RNA: Insights into riboswitch discernment of the tRNA discriminator base

PubMed Central

Means, John A.; Simson, Crystal M.; Zhou, Shu; Rachford, Aaron A.; Rack, Jeffrey J.; Hines, Jennifer V.

2009-01-01

The T box transcription antitermination riboswitch is one of the main regulatory mechanisms utilized by Gram-positive bacteria to regulate genes that are involved in amino acid metabolism. The details of the antitermination event, including the role that Mg2+ plays, in this riboswitch have not been completely elucidated. In these studies, details of the antitermination event were investigated utilizing 2-aminopurine to monitor structural changes of a model antiterminator RNA when it was bound to model tRNA. Based on the results of these fluorescence studies, the model tRNA binds the model antiterminator RNA via an induced fit. This binding is enhanced by the presence of Mg2+, facilitating the complete base pairing of the model tRNA acceptor end with the complementary bases in the model antiterminator bulge. PMID:19755116

Local Structure and Surface Properties of CoxZn1-xO Thin Films for Ozone Gas Sensing.

PubMed

Catto, Ariadne C; Silva, Luís F da; Bernardi, Maria Inês B; Bernardini, Sandrine; Aguir, Khalifa; Longo, Elson; Mastelaro, Valmor R

2016-10-05

A detailed study of the structural, surface, and gas-sensing properties of nanostructured Co x Zn 1-x O films is presented. X-ray diffraction (XRD) analysis revealed a decrease in the crystallization degree with increasing Co content. The X-ray absorption near-edge structure (XANES) and X-ray photoelectron spectroscopies (XPS) revealed that the Co 2+ ions preferentially occupied the Zn 2+ sites and that the oxygen vacancy concentration increased as the amount of cobalt increased. Electrical measurements showed that the Co dopants not only enhanced the sensor response at low ozone levels (ca. 42 ppb) but also led to a decrease in the operating temperature and improved selectivity. The enhancement in the gas-sensing properties was attributed to the presence of oxygen vacancies, which facilitated ozone adsorption.

Structure determination of a major facilitator peptide transporter: Inward facing PepTSt from Streptococcus thermophilus crystallized in space group P3121

PubMed Central

Quistgaard, Esben M.; Martinez Molledo, Maria

2017-01-01

Major facilitator superfamily (MFS) peptide transporters (typically referred to as PepT, POT or PTR transporters) mediate the uptake of di- and tripeptides, and so play an important dietary role in many organisms. In recent years, a better understanding of the molecular basis for this process has emerged, which is in large part due to a steep increase in structural information. Yet, the conformational transitions underlying the transport mechanism are still not fully understood, and additional data is therefore needed. Here we report in detail the detergent screening, crystallization, experimental MIRAS phasing, and refinement of the peptide transporter PepTSt from Streptococcus thermophilus. The space group is P3121, and the protein is crystallized in a monomeric inward facing form. The binding site is likely to be somewhat occluded, as the lobe encompassing transmembrane helices 10 and 11 is markedly bent towards the central pore of the protein, but the extent of this potential occlusion could not be determined due to disorder at the apex of the lobe. Based on structural comparisons with the seven previously determined P212121 and C2221 structures of inward facing PepTSt, the structural flexibility as well as the conformational changes mediating transition between the inward open and inward facing occluded states are discussed. In conclusion, this report improves our understanding of the structure and conformational cycle of PepTSt, and can furthermore serve as a case study, which may aid in supporting future structure determinations of additional MFS transporters or other integral membrane proteins. PMID:28264013

Smart wing wind tunnel model design

NASA Astrophysics Data System (ADS)

Martin, Christopher A.; Jasmin, Larry; Flanagan, John S.; Appa, Kari; Kudva, Jayanth N.

1997-05-01

To verify the predicted benefits of the smart wing concept, two 16% scale wind tunnel models, one conventional and the other incorporating smart wing design features, were designed, fabricated and tested. Meticulous design of the two models was essential to: (1) ensure the required factor of safety of four for operation in the NASA Langley TDT wind tunnel, (2) efficiently integrate the smart actuation systems, (3) quantify the performance improvements, and (4) facilitate eventual scale-up to operational aircraft. Significant challenges were encountered in designing the attachment of the shape memory alloy control surfaces to the wing box, integration of the SMA torque tube in the wing structure, and development of control mechanisms to protect the model and the tunnel in the event of failure of the smart systems. In this paper, detailed design of the two models are presented. First, dynamic scaling of the models based on the geometry and structural details of the full- scale aircraft is presented. Next, results of the stress, divergence and flutter analyses are summarized. Finally some of the challenges of integrating the smart actuators with the model are highlighted.

Preparing and Restoring Composite Resin Restorations. The Advantage of High Magnification Loupes or the Dental Surgical Operating Microscope.

PubMed

Mamoun, John

2015-01-01

Use of magnification, such as 6x to 8x binocular surgical loupes or the surgical operating microscope, combined with co-axial illumination, may facilitate the creation of stable composite resin restorations that are less likely to develop caries, cracks or margin stains over years of service. Microscopes facilitate observation of clinically relevant microscopic visual details, such as microscopic amounts of demineralization or caries at preparation margins; microscopic areas of soft, decayed tooth structure; microscopic amounts of moisture contamination of the preparation during bonding; or microscopic marginal gaps in the composite. Preventing microscope-level errors in composite fabrication can result in a composite restoration that, at initial placement, appears perfect when viewed under 6x to 8x magnification and which also is free of secondary caries, marginal staining or cracks at multi-year follow-up visits.

First structure of full-length mammalian phenylalanine hydroxylase reveals the architecture of an autoinhibited tetramer

PubMed Central

Arturo, Emilia C.; Gupta, Kushol; Héroux, Annie; Stith, Linda; Cross, Penelope J.; Parker, Emily J.; Loll, Patrick J.; Jaffe, Eileen K.

2016-01-01

Improved understanding of the relationship among structure, dynamics, and function for the enzyme phenylalanine hydroxylase (PAH) can lead to needed new therapies for phenylketonuria, the most common inborn error of amino acid metabolism. PAH is a multidomain homo-multimeric protein whose conformation and multimerization properties respond to allosteric activation by the substrate phenylalanine (Phe); the allosteric regulation is necessary to maintain Phe below neurotoxic levels. A recently introduced model for allosteric regulation of PAH involves major domain motions and architecturally distinct PAH tetramers [Jaffe EK, Stith L, Lawrence SH, Andrake M, Dunbrack RL, Jr (2013) Arch Biochem Biophys 530(2):73–82]. Herein, we present, to our knowledge, the first X-ray crystal structure for a full-length mammalian (rat) PAH in an autoinhibited conformation. Chromatographic isolation of a monodisperse tetrameric PAH, in the absence of Phe, facilitated determination of the 2.9 Å crystal structure. The structure of full-length PAH supersedes a composite homology model that had been used extensively to rationalize phenylketonuria genotype–phenotype relationships. Small-angle X-ray scattering (SAXS) confirms that this tetramer, which dominates in the absence of Phe, is different from a Phe-stabilized allosterically activated PAH tetramer. The lack of structural detail for activated PAH remains a barrier to complete understanding of phenylketonuria genotype–phenotype relationships. Nevertheless, the use of SAXS and X-ray crystallography together to inspect PAH structure provides, to our knowledge, the first complete view of the enzyme in a tetrameric form that was not possible with prior partial crystal structures, and facilitates interpretation of a wealth of biochemical and structural data that was hitherto impossible to evaluate. PMID:26884182

Ligand-Induced Stabilization of a Duplex-like Architecture Is Crucial for the Switching Mechanism of the SAM-III Riboswitch.

PubMed

Suresh, Gorle; Srinivasan, Harini; Nanda, Shivani; Priyakumar, U Deva

2016-06-21

Riboswitches are structured RNA motifs that control gene expression by sensing the concentrations of specific metabolites and make up a promising new class of antibiotic targets. S-Adenosylmethionine (SAM)-III riboswitch, mainly found in lactic acid bacteria, is involved in regulating methionine and SAM biosynthetic pathways. SAM-III riboswitch regulates the gene expression by switching the translation process on and off with respect to the absence and presence of the SAM ligand, respectively. In this study, an attempt is made to understand the key conformational transitions involved in ligand binding using atomistic molecular dynamics (MD) simulations performed in an explicit solvent environment. G26 is found to recognize the SAM ligand by forming hydrogen bonds, whereas the absence of the ligand leads to opening of the binding pocket. Consistent with experimental results, the absence of the SAM ligand weakens the base pairing interactions between the nucleobases that are part of the Shine-Dalgarno (SD) and anti-Shine-Dalgarno (aSD) sequences, which in turn facilitates recognition of the SD sequence by ribosomes. Detailed analysis reveals that a duplex-like structure formed by nucleotides from different parts of the RNA and the adenine base of the ligand is crucial for the stability of the completely folded state in the presence of the ligand. Previous experimental studies have shown that the SAM-III riboswitch exists in equilibrium between the unfolded and partially folded states in the absence of the ligand, which completely folds upon binding of the ligand. Comparison of the results presented here to the available experimental data indicates the structures obtained using the MD simulations resemble the partially folded state. Thus, this study provides a detailed understanding of the fully and partially folded structures of the SAM-III riboswitch in the presence and absence of the ligand, respectively. This study hypothesizes a dual role for the SAM ligand, which facilitates conformational switching between partially and fully folded states by forming a stable duplex-like structure and strengthening the interactions between SD and aSD nucleotides.

The development and implementation of a theory-informed, integrated mother-child intervention in rural Uganda.

PubMed

Singla, Daisy R; Kumbakumba, Elias

2015-12-01

A randomised cluster effectiveness trial of a parenting intervention in rural Uganda found benefits to child development among children 12-36 months, relevant parenting practices related to stimulation, hygiene and diet, and prevented the worsening of mothers' depressive symptoms. An examination of underlying implementation processes allows researchers and program developers to determine whether the program was implemented as intended and highlight barriers and facilitators that may influence replication and scale-up. The objectives of this study were to describe and critically examine (a) perceived barriers and facilitators related to implementation processes of intervention content, training and supervision and delivery from the perspectives of delivery agents and supervisors; (b) perceived barriers and facilitators related to enactment of practices from the perspective of intervention mothers participating in the parenting program; and c) whether the program was implemented as intended. Semi-structured interviews were conducted at midline with peer delivery agents (n = 12) and intervention mothers (n = 31) and at endline with supervisors (n = 4). Content analysis was used to analyze qualitative data in terms of barriers and facilitators of intervention content, training and supervision, delivery and enactment. Additionally, mothers' recall and enactment of practices were coded and analyzed statistically. Monitoring of group sessions and home visits were examined to reveal whether the program was implemented as intended. Among the program's five key messages, 'love and respect' targeting maternal psychological well-being was the most practiced by mothers, easiest to implement by delivery agents, and mothers reported the most internal facilitators for this message. A detailed manual and structured monitoring forms were perceived to facilitate training, intervention delivery, and supervision. Interactive and active strategies based on social-cognitive learning theory were reported as facilitators to intervention delivery. Only program attendance, but not barriers, facilitators or message recall, was significantly positively related to message enactment. Monitoring of group sessions and home visits showed that the program was largely implemented as intended. This implementation assessment revealed a number of important barriers and facilitators from the perspectives of delivery agents, supervisors and program participants. The methods and results are useful to examining and informing the content, delivery, and scaling up of the current program as well as future mother-child interventions in LMIC settings. Copyright © 2015 Elsevier Ltd. All rights reserved.

Barriers and Facilitators to Adoption of Genomic Services for Colorectal Care within the Veterans Health Administration.

PubMed

Sperber, Nina R; Andrews, Sara M; Voils, Corrine I; Green, Gregory L; Provenzale, Dawn; Knight, Sara

2016-04-28

We examined facilitators and barriers to adoption of genomic services for colorectal care, one of the first genomic medicine applications, within the Veterans Health Administration to shed light on areas for practice change. We conducted semi-structured interviews with 58 clinicians to understand use of the following genomic services for colorectal care: family health history documentation, molecular and genetic testing, and genetic counseling. Data collection and analysis were informed by two conceptual frameworks, the Greenhalgh Diffusion of Innovation and Andersen Behavioral Model, to allow for concurrent examination of both access and innovation factors. Specialists were more likely than primary care clinicians to obtain family history to investigate hereditary colorectal cancer (CRC), but with limited detail; clinicians suggested templates to facilitate retrieval and documentation of family history according to guidelines. Clinicians identified advantage of molecular tumor analysis prior to genetic testing, but tumor testing was infrequently used due to perceived low disease burden. Support from genetic counselors was regarded as facilitative for considering hereditary basis of CRC diagnosis, but there was variability in awareness of and access to this expertise. Our data suggest the need for tools and policies to establish and disseminate well-defined processes for accessing services and adhering to guidelines.

What do parents perceive are the barriers and facilitators to accessing psychological treatment for mental health problems in children and adolescents? A systematic review of qualitative and quantitative studies.

PubMed

Reardon, Tessa; Harvey, Kate; Baranowska, Magdalena; O'Brien, Doireann; Smith, Lydia; Creswell, Cathy

2017-06-01

A minority of children and adolescents with mental health problems access treatment. The reasons for poor rates of treatment access are not well understood. As parents are a key gatekeeper to treatment access, it is important to establish parents' views of barriers/facilitators to accessing treatment. The aims of this study are to synthesise findings from qualitative and quantitative studies that report parents' perceptions of barriers/facilitators to accessing treatment for mental health problems in children/adolescents. A systematic review and narrative synthesis were conducted. Forty-four studies were included in the review and were assessed in detail. Parental perceived barriers/facilitators relating to (1) systemic/structural issues; (2) views and attitudes towards services and treatment; (3) knowledge and understanding of mental health problems and the help-seeking process; and (4) family circumstances were identified. Findings highlight avenues for improving access to child mental health services, including increased provision that is free to service users and flexible to their needs, with opportunities to develop trusting, supportive relationships with professionals. Furthermore, interventions are required to improve parents' identification of mental health problems, reduce stigma for parents, and increase awareness of how to access services.

The Dynamics of Syntax Acquisition: Facilitation between Syntactic Structures

ERIC Educational Resources Information Center

Keren-Portnoy, Tamar; Keren, Michael

2011-01-01

This paper sets out to show how facilitation between different clause structures operates over time in syntax acquisition. The phenomenon of facilitation within given structures has been widely documented, yet inter-structure facilitation has rarely been reported so far. Our findings are based on the naturalistic production corpora of six toddlers…

Heterogeneous structure and surface tension effects on mechanical response in pulmonary acinus: A finite element analysis.

PubMed

Koshiyama, Kenichiro; Nishimoto, Keisuke; Ii, Satoshi; Sera, Toshihiro; Wada, Shigeo

2018-01-20

The pulmonary acinus is a dead-end microstructure that consists of ducts and alveoli. High-resolution micro-CT imaging has recently provided detailed anatomical information of a complete in vivo acinus, but relating its mechanical response with its detailed acinar structure remains challenging. This study aimed to investigate the mechanical response of acinar tissue in a whole acinus for static inflation using computational approaches. We performed finite element analysis of a whole acinus for static inflation. The acinar structure model was generated based on micro-CT images of an intact acinus. A continuum mechanics model of the lung parenchyma was used for acinar tissue material model, and surface tension effects were explicitly included. An anisotropic mechanical field analysis based on a stretch tensor was combined with a curvature-based local structure analysis. The airspace of the acinus exhibited nonspherical deformation as a result of the anisotropic deformation of acinar tissue. A strain hotspot occurred at the ridge-shaped region caused by a rod-like deformation of acinar tissue on the ridge. The local structure becomes bowl-shaped for inflation and, without surface tension effects, the surface of the bowl-shaped region primarily experiences isotropic deformation. Surface tension effects suppressed the increase in airspace volume and inner surface area, while facilitating anisotropic deformation on the alveolar surface. In the lungs, the heterogeneous acinar structure and surface tension induce anisotropic deformation at the acinar and alveolar scales. Further research is needed on structural variation of acini, inter-acini connectivity, or dynamic behavior to understand multiscale lung mechanics. Copyright © 2018 Elsevier Ltd. All rights reserved.

Oncogenic Mutations Differentially Affect Bax Monomer, Dimer, and Oligomeric Pore Formation in the Membrane.

PubMed

Zhang, Mingzhen; Zheng, Jie; Nussinov, Ruth; Ma, Buyong

2016-09-15

Dysfunction of Bax, a pro-apoptotic regulator of cellular metabolism is implicated in neurodegenerative diseases and cancer. We have constructed the first atomistic models of the Bax oligomeric pore consisting with experimental residue-residue distances. The models are stable, capturing well double electron-electron resonance (DEER) spectroscopy measurements and provide structural details in line with the DEER data. Comparison with the latest experimental results revealed that our models agree well with both Bax and Bak pores, pointed to a converged structural arrangement for Bax and Bak pore formation. Using multi-scale molecular dynamics simulations, we probed mutational effects on Bax transformation from monomer → dimer → membrane pore formation at atomic resolution. We observe that two cancer-related mutations, G40E and S118I, allosterically destabilize the monomer and stabilize an off-pathway swapped dimer, preventing productive pore formation. This observation suggests a mechanism whereby the mutations may work mainly by over-stabilizing the monomer → dimer transformation toward an unproductive off-pathway swapped-dimer state. Our observations point to misfolded Bax states, shedding light on the molecular mechanism of Bax mutation-elicited cancer. Most importantly, the structure of the Bax pore facilitates future study of releases cytochrome C in atomic detail.

Oncogenic Mutations Differentially Affect Bax Monomer, Dimer, and Oligomeric Pore Formation in the Membrane

NASA Astrophysics Data System (ADS)

Zhang, Mingzhen; Zheng, Jie; Nussinov, Ruth; Ma, Buyong

2016-09-01

Dysfunction of Bax, a pro-apoptotic regulator of cellular metabolism is implicated in neurodegenerative diseases and cancer. We have constructed the first atomistic models of the Bax oligomeric pore consisting with experimental residue-residue distances. The models are stable, capturing well double electron-electron resonance (DEER) spectroscopy measurements and provide structural details in line with the DEER data. Comparison with the latest experimental results revealed that our models agree well with both Bax and Bak pores, pointed to a converged structural arrangement for Bax and Bak pore formation. Using multi-scale molecular dynamics simulations, we probed mutational effects on Bax transformation from monomer → dimer → membrane pore formation at atomic resolution. We observe that two cancer-related mutations, G40E and S118I, allosterically destabilize the monomer and stabilize an off-pathway swapped dimer, preventing productive pore formation. This observation suggests a mechanism whereby the mutations may work mainly by over-stabilizing the monomer → dimer transformation toward an unproductive off-pathway swapped-dimer state. Our observations point to misfolded Bax states, shedding light on the molecular mechanism of Bax mutation-elicited cancer. Most importantly, the structure of the Bax pore facilitates future study of releases cytochrome C in atomic detail.

Architecture with GIDEON, A Program for Design in Structural DNA Nanotechnology

PubMed Central

Birac, Jeffrey J.; Sherman, William B.; Kopatsch, Jens; Constantinou, Pamela E.; Seeman, Nadrian C.

2012-01-01

We present geometry based design strategies for DNA nanostructures. The strategies have been implemented with GIDEON – a Graphical Integrated Development Environment for OligoNucleotides. GIDEON has a highly flexible graphical user interface that facilitates the development of simple yet precise models, and the evaluation of strains therein. Models are built on a simple model of undistorted B-DNA double-helical domains. Simple point and click manipulations of the model allow the minimization of strain in the phosphate-backbone linkages between these domains and the identification of any steric clashes that might occur as a result. Detailed analysis of 3D triangles yields clear predictions of the strains associated with triangles of different sizes. We have carried out experiments that confirm that 3D triangles form well only when their geometrical strain is less than 4% deviation from the estimated relaxed structure. Thus geometry-based techniques alone, without energetic considerations, can be used to explain general trends in DNA structure formation. We have used GIDEON to build detailed models of double crossover and triple crossover molecules, evaluating the non-planarity associated with base tilt and junction mis-alignments. Computer modeling using a graphical user interface overcomes the limited precision of physical models for larger systems, and the limited interaction rate associated with earlier, command-line driven software. PMID:16630733

Portable ultrahigh-vacuum sample storage system for polarization-dependent total-reflection fluorescence x-ray absorption fine structure spectroscopy

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

Watanabe, Yoshihide, E-mail: e0827@mosk.tytlabs.co.jp; Nishimura, Yusaku F.; Suzuki, Ryo

A portable ultrahigh-vacuum sample storage system was designed and built to investigate the detailed geometric structures of mass-selected metal clusters on oxide substrates by polarization-dependent total-reflection fluorescence x-ray absorption fine structure spectroscopy (PTRF-XAFS). This ultrahigh-vacuum (UHV) sample storage system provides the handover of samples between two different sample manipulating systems. The sample storage system is adaptable for public transportation, facilitating experiments using air-sensitive samples in synchrotron radiation or other quantum beam facilities. The samples were transferred by the developed portable UHV transfer system via a public transportation at a distance over 400 km. The performance of the transfer system was demonstratedmore » by a successful PTRF-XAFS study of Pt{sub 4} clusters deposited on a TiO{sub 2}(110) surface.« less

Coarse-grained mechanics of viral shells

NASA Astrophysics Data System (ADS)

Klug, William S.; Gibbons, Melissa M.

2008-03-01

We present an approach for creating three-dimensional finite element models of viral capsids from atomic-level structural data (X-ray or cryo-EM). The models capture heterogeneous geometric features and are used in conjunction with three-dimensional nonlinear continuum elasticity to simulate nanoindentation experiments as performed using atomic force microscopy. The method is extremely flexible; able to capture varying levels of detail in the three-dimensional structure. Nanoindentation simulations are presented for several viruses: Hepatitis B, CCMV, HK97, and φ29. In addition to purely continuum elastic models a multiscale technique is developed that combines finite-element kinematics with MD energetics such that large-scale deformations are facilitated by a reduction in degrees of freedom. Simulations of these capsid deformation experiments provide a testing ground for the techniques, as well as insight into the strength-determining mechanisms of capsid deformation. These methods can be extended as a framework for modeling other proteins and macromolecular structures in cell biology.

Computational biology approach to uncover hepatitis C virus helicase operation.

PubMed

Flechsig, Holger

2014-04-07

Hepatitis C virus (HCV) helicase is a molecular motor that splits nucleic acid duplex structures during viral replication, therefore representing a promising target for antiviral treatment. Hence, a detailed understanding of the mechanism by which it operates would facilitate the development of efficient drug-assisted therapies aiming to inhibit helicase activity. Despite extensive investigations performed in the past, a thorough understanding of the activity of this important protein was lacking since the underlying internal conformational motions could not be resolved. Here we review investigations that have been previously performed by us for HCV helicase. Using methods of structure-based computational modelling it became possible to follow entire operation cycles of this motor protein in structurally resolved simulations and uncover the mechanism by which it moves along the nucleic acid and accomplishes strand separation. We also discuss observations from that study in the light of recent experimental studies that confirm our findings.

The NASA computer aided design and test system

NASA Technical Reports Server (NTRS)

Gould, J. M.; Juergensen, K.

1973-01-01

A family of computer programs facilitating the design, layout, evaluation, and testing of digital electronic circuitry is described. CADAT (computer aided design and test system) is intended for use by NASA and its contractors and is aimed predominantly at providing cost effective microelectronic subsystems based on custom designed metal oxide semiconductor (MOS) large scale integrated circuits (LSIC's). CADAT software can be easily adopted by installations with a wide variety of computer hardware configurations. Its structure permits ease of update to more powerful component programs and to newly emerging LSIC technologies. The components of the CADAT system are described stressing the interaction of programs rather than detail of coding or algorithms. The CADAT system provides computer aids to derive and document the design intent, includes powerful automatic layout software, permits detailed geometry checks and performance simulation based on mask data, and furnishes test pattern sequences for hardware testing.

NALDB: nucleic acid ligand database for small molecules targeting nucleic acid.

PubMed

Kumar Mishra, Subodh; Kumar, Amit

2016-01-01

Nucleic acid ligand database (NALDB) is a unique database that provides detailed information about the experimental data of small molecules that were reported to target several types of nucleic acid structures. NALDB is the first ligand database that contains ligand information for all type of nucleic acid. NALDB contains more than 3500 ligand entries with detailed pharmacokinetic and pharmacodynamic information such as target name, target sequence, ligand 2D/3D structure, SMILES, molecular formula, molecular weight, net-formal charge, AlogP, number of rings, number of hydrogen bond donor and acceptor, potential energy along with their Ki, Kd, IC50 values. All these details at single platform would be helpful for the development and betterment of novel ligands targeting nucleic acids that could serve as a potential target in different diseases including cancers and neurological disorders. With maximum 255 conformers for each ligand entry, our database is a multi-conformer database and can facilitate the virtual screening process. NALDB provides powerful web-based search tools that make database searching efficient and simplified using option for text as well as for structure query. NALDB also provides multi-dimensional advanced search tool which can screen the database molecules on the basis of molecular properties of ligand provided by database users. A 3D structure visualization tool has also been included for 3D structure representation of ligands. NALDB offers an inclusive pharmacological information and the structurally flexible set of small molecules with their three-dimensional conformers that can accelerate the virtual screening and other modeling processes and eventually complement the nucleic acid-based drug discovery research. NALDB can be routinely updated and freely available on bsbe.iiti.ac.in/bsbe/naldb/HOME.php. Database URL: http://bsbe.iiti.ac.in/bsbe/naldb/HOME.php. © The Author(s) 2016. Published by Oxford University Press.

Subangstrom resolution X-ray structure details aquaporin-water interactions.

PubMed

Eriksson, Urszula Kosinska; Fischer, Gerhard; Friemann, Rosmarie; Enkavi, Giray; Tajkhorshid, Emad; Neutze, Richard

2013-06-14

Aquaporins are membrane channels that facilitate the flow of water across biological membranes. Two conserved regions are central for selective function: the dual asparagine-proline-alanine (NPA) aquaporin signature motif and the aromatic and arginine selectivity filter (SF). Here, we present the crystal structure of a yeast aquaporin at 0.88 angstrom resolution. We visualize the H-bond donor interactions of the NPA motif's asparagine residues to passing water molecules; observe a polarized water-water H-bond configuration within the channel; assign the tautomeric states of the SF histidine and arginine residues; and observe four SF water positions too closely spaced to be simultaneously occupied. Strongly correlated movements break the connectivity of SF waters to other water molecules within the channel and prevent proton transport via a Grotthuss mechanism.

Membrane association and localization dynamics of the Ebola virus matrix protein VP40.

PubMed

Gc, Jeevan B; Gerstman, Bernard S; Chapagain, Prem P

2017-10-01

The Ebola virus matrix protein VP40 is a major structural protein that provides the scaffolding for new Ebola virus particles. For this, VP40 is first trafficked to the lower leaflet of the plasma membrane (PM) in its dimeric form. Once associated with the PM, the VP40 dimers undergo structural rearrangements and oligomerize into hexamers and filaments that make up the virus matrix. Therefore, association of the VP40 dimers and their stabilization at the PM is a crucial step in the Ebola life-cycle. To understand the molecular details of the VP40 dimer-PM interactions, we investigated the dimer association with the inner leaflet of the PM using detailed all-atom molecular dynamics (MD) simulations. The formation of the dimer-PM complex is facilitated by the interactions of the VP40 lysine residues and the anionic lipids POPS, POPI, and PIP 2 in the PM. In contrast, the dimer fails to associate with a membrane without POPS, POPI, or PIP 2 lipids. We explored the mechanisms of the association and identified important residues and lipids involved in localization and stabilization of VP40 dimers at the PM. MD simulations elucidate the role of a C-terminal α-helix alignment parallel to the lipid bilayer surface as well as the creation of membrane defects that allow partial insertion of the hydrophobic residue V276 into the membrane to further stabilize the VP40 dimer-PM complex. Understanding the mechanisms of the VP40 dimer-PM association that facilitate oligomerization can be important for potentially targeting the VP40 for small molecules that can interfere with the virus life-cycle. Copyright © 2017 Elsevier B.V. All rights reserved.

Adaptive Modeling, Engineering Analysis and Design of Advanced Aerospace Vehicles

NASA Technical Reports Server (NTRS)

Mukhopadhyay, Vivek; Hsu, Su-Yuen; Mason, Brian H.; Hicks, Mike D.; Jones, William T.; Sleight, David W.; Chun, Julio; Spangler, Jan L.; Kamhawi, Hilmi; Dahl, Jorgen L.

2006-01-01

This paper describes initial progress towards the development and enhancement of a set of software tools for rapid adaptive modeling, and conceptual design of advanced aerospace vehicle concepts. With demanding structural and aerodynamic performance requirements, these high fidelity geometry based modeling tools are essential for rapid and accurate engineering analysis at the early concept development stage. This adaptive modeling tool was used for generating vehicle parametric geometry, outer mold line and detailed internal structural layout of wing, fuselage, skin, spars, ribs, control surfaces, frames, bulkheads, floors, etc., that facilitated rapid finite element analysis, sizing study and weight optimization. The high quality outer mold line enabled rapid aerodynamic analysis in order to provide reliable design data at critical flight conditions. Example application for structural design of a conventional aircraft and a high altitude long endurance vehicle configuration are presented. This work was performed under the Conceptual Design Shop sub-project within the Efficient Aerodynamic Shape and Integration project, under the former Vehicle Systems Program. The project objective was to design and assess unconventional atmospheric vehicle concepts efficiently and confidently. The implementation may also dramatically facilitate physics-based systems analysis for the NASA Fundamental Aeronautics Mission. In addition to providing technology for design and development of unconventional aircraft, the techniques for generation of accurate geometry and internal sub-structure and the automated interface with the high fidelity analysis codes could also be applied towards the design of vehicles for the NASA Exploration and Space Science Mission projects.

Historic Bim: a New Repository for Structural Health Monitoring

NASA Astrophysics Data System (ADS)

Banfi, F.; Barazzetti, L.; Previtali, M.; Roncoroni, F.

2017-05-01

Recent developments in Building Information Modelling (BIM) technologies are facilitating the management of historic complex structures using new applications. This paper proposes a generative method combining the morphological and typological aspects of the historic buildings (H-BIM), with a set of monitoring information. This combination of 3D digital survey, parametric modelling and monitoring datasets allows for the development of a system for archiving and visualizing structural health monitoring (SHM) data (Fig. 1). The availability of a BIM database allows one to integrate a different kind of data stored in different ways (e.g. reports, tables, graphs, etc.) with a representation directly connected to the 3D model of the structure with appropriate levels of detail (LoD). Data can be interactively accessed by selecting specific objects of the BIM, i.e. connecting the 3D position of the sensors installed with additional digital documentation. Such innovative BIM objects, which form a new BIM family for SHM, can be then reused in other projects, facilitating data archiving and exploitation of data acquired and processed. The application of advanced modeling techniques allows for the reduction of time and costs of the generation process, and support cooperation between different disciplines using a central workspace. However, it also reveals new challenges for parametric software and exchange formats. The case study presented is the medieval bridge Azzone Visconti in Lecco (Italy), in which multi-temporal vertical movements during load testing were integrated into H-BIM.

Chemical Proteomics and Structural Biology Define EPHA2 Inhibition by Clinical Kinase Drugs.

PubMed

Heinzlmeir, Stephanie; Kudlinzki, Denis; Sreeramulu, Sridhar; Klaeger, Susan; Gande, Santosh Lakshmi; Linhard, Verena; Wilhelm, Mathias; Qiao, Huichao; Helm, Dominic; Ruprecht, Benjamin; Saxena, Krishna; Médard, Guillaume; Schwalbe, Harald; Kuster, Bernhard

2016-12-16

The receptor tyrosine kinase EPHA2 (Ephrin type-A receptor 2) plays important roles in oncogenesis, metastasis, and treatment resistance, yet therapeutic targeting, drug discovery, or investigation of EPHA2 biology is hampered by the lack of appropriate inhibitors and structural information. Here, we used chemical proteomics to survey 235 clinical kinase inhibitors for their kinase selectivity and identified 24 drugs with submicromolar affinities for EPHA2. NMR-based conformational dynamics together with nine new cocrystal structures delineated drug-EPHA2 interactions in full detail. The combination of selectivity profiling, structure determination, and kinome wide sequence alignment allowed the development of a classification system in which amino acids in the drug binding site of EPHA2 are categorized into key, scaffold, potency, and selectivity residues. This scheme should be generally applicable in kinase drug discovery, and we anticipate that the provided information will greatly facilitate the development of selective EPHA2 inhibitors in particular and the repurposing of clinical kinase inhibitors in general.

DichroCalc: Improvements in Computing Protein Circular Dichroism Spectroscopy in the Near-Ultraviolet.

PubMed

Jasim, Sarah B; Li, Zhuo; Guest, Ellen E; Hirst, Jonathan D

2017-12-16

A fully quantitative theory connecting protein conformation and optical spectroscopy would facilitate deeper insights into biophysical and simulation studies of protein dynamics and folding. The web server DichroCalc (http://comp.chem.nottingham.ac.uk/dichrocalc) allows one to compute from first principles the electronic circular dichroism spectrum of a (modeled or experimental) protein structure or ensemble of structures. The regular, repeating, chiral nature of secondary structure elements leads to intense bands in the far-ultraviolet (UV). The near-UV bands are much weaker and have been challenging to compute theoretically. We report some advances in the accuracy of calculations in the near-UV, realized through the consideration of the vibrational structure of the electronic transitions of aromatic side chains. The improvements have been assessed over a set of diverse proteins. We illustrate them using bovine pancreatic trypsin inhibitor and present a new, detailed analysis of the interactions which are most important in determining the near-UV circular dichroism spectrum. Copyright © 2018. Published by Elsevier Ltd.

Sequential protein unfolding through a carbon nanotube pore

NASA Astrophysics Data System (ADS)

Xu, Zhonghe; Zhang, Shuang; Weber, Jeffrey K.; Luan, Binquan; Zhou, Ruhong; Li, Jingyuan

2016-06-01

An assortment of biological processes, like protein degradation and the transport of proteins across membranes, depend on protein unfolding events mediated by nanopore interfaces. In this work, we exploit fully atomistic simulations of an artificial, CNT-based nanopore to investigate the nature of ubiquitin unfolding. With one end of the protein subjected to an external force, we observe non-canonical unfolding behaviour as ubiquitin is pulled through the pore opening. Secondary structural elements are sequentially detached from the protein and threaded into the nanotube, interestingly, the remaining part maintains native-like characteristics. The constraints of the nanopore interface thus facilitate the formation of stable ``unfoldon'' motifs above the nanotube aperture that can exist in the absence of specific native contacts with the other secondary structure. Destruction of these unfoldons gives rise to distinct force peaks in our simulations, providing us with a sensitive probe for studying the kinetics of serial unfolding events. Our detailed analysis of nanopore-mediated protein unfolding events not only provides insight into how related processes might proceed in the cell, but also serves to deepen our understanding of structural arrangements which form the basis for protein conformational stability.An assortment of biological processes, like protein degradation and the transport of proteins across membranes, depend on protein unfolding events mediated by nanopore interfaces. In this work, we exploit fully atomistic simulations of an artificial, CNT-based nanopore to investigate the nature of ubiquitin unfolding. With one end of the protein subjected to an external force, we observe non-canonical unfolding behaviour as ubiquitin is pulled through the pore opening. Secondary structural elements are sequentially detached from the protein and threaded into the nanotube, interestingly, the remaining part maintains native-like characteristics. The constraints of the nanopore interface thus facilitate the formation of stable ``unfoldon'' motifs above the nanotube aperture that can exist in the absence of specific native contacts with the other secondary structure. Destruction of these unfoldons gives rise to distinct force peaks in our simulations, providing us with a sensitive probe for studying the kinetics of serial unfolding events. Our detailed analysis of nanopore-mediated protein unfolding events not only provides insight into how related processes might proceed in the cell, but also serves to deepen our understanding of structural arrangements which form the basis for protein conformational stability. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr00410e

The use of porcine corrosion casts for teaching human anatomy.

PubMed

Eberlova, Lada; Liska, Vaclav; Mirka, Hynek; Tonar, Zbynek; Haviar, Stanislav; Svoboda, Milos; Benes, Jan; Palek, Richard; Emingr, Michal; Rosendorf, Jachym; Mik, Patrik; Leupen, Sarah; Lametschwandtner, Alois

2017-09-01

In teaching and learning human anatomy, anatomical autopsy and prosected specimens have always been indispensable. However, alternative methods must often be used to demonstrate particularly delicate structures. Corrosion casting of porcine organs with Biodur E20 ® Plus is valuable for teaching and learning both gross anatomy and, uniquely, the micromorphology of cardiovascular, respiratory, digestive, and urogenital systems. Assessments of casts with a stereomicroscope and/or scanning electron microscope as well as highlighting cast structures using color coding help students to better understand how the structures that they have observed as two-dimensional images actually exist in three dimensions, and students found using the casts to be highly effective in their learning. Reconstructions of cast hollow structures from (micro-)computed tomography scans and videos facilitate detailed analyses of branching patterns and spatial arrangements in cast structures, aid in the understanding of clinically relevant structures and provide innovative visual aids. The casting protocol and teaching manual we offer can be adjusted to different technical capabilities and might also be found useful for veterinary or other biological science classes. Copyright © 2017 Elsevier GmbH. All rights reserved.

An interactive three-dimensional virtual body structures system for anatomical training over the internet.

PubMed

Temkin, Bharti; Acosta, Eric; Malvankar, Ameya; Vaidyanath, Sreeram

2006-04-01

The Visible Human digital datasets make it possible to develop computer-based anatomical training systems that use virtual anatomical models (virtual body structures-VBS). Medical schools are combining these virtual training systems and classical anatomy teaching methods that use labeled images and cadaver dissection. In this paper we present a customizable web-based three-dimensional anatomy training system, W3D-VBS. W3D-VBS uses National Library of Medicine's (NLM) Visible Human Male datasets to interactively locate, explore, select, extract, highlight, label, and visualize, realistic 2D (using axial, coronal, and sagittal views) and 3D virtual structures. A real-time self-guided virtual tour of the entire body is designed to provide detailed anatomical information about structures, substructures, and proximal structures. The system thus facilitates learning of visuospatial relationships at a level of detail that may not be possible by any other means. The use of volumetric structures allows for repeated real-time virtual dissections, from any angle, at the convenience of the user. Volumetric (3D) virtual dissections are performed by adding, removing, highlighting, and labeling individual structures (and/or entire anatomical systems). The resultant virtual explorations (consisting of anatomical 2D/3D illustrations and animations), with user selected highlighting colors and label positions, can be saved and used for generating lesson plans and evaluation systems. Tracking users' progress using the evaluation system helps customize the curriculum, making W3D-VBS a powerful learning tool. Our plan is to incorporate other Visible Human segmented datasets, especially datasets with higher resolutions, that make it possible to include finer anatomical structures such as nerves and small vessels. (c) 2006 Wiley-Liss, Inc.

Does "Sneaky Fox" Facilitate Learning? Examining the Effects of Seductive Details in Physical Education

ERIC Educational Resources Information Center

Shen, Bo; McCaughtry, Nate; Martin, Jeffrey; Dillion, Suzanna

2006-01-01

While seductive details are enjoyable, they are unimportant content or activities intentionally inserted to make class fun and interesting. The purpose of this study was to examine the effect of seductive details on students' learning of net games in physical education. Participants were 240 middle school students. A videotaped lesson example…

Investigation of type-I interferon dysregulation by arenaviruses : a multidisciplinary approach.

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

Kozina, Carol L.; Moorman, Matthew Wallace; Branda, Catherine

2011-09-01

This report provides a detailed overview of the work performed for project number 130781, 'A Systems Biology Approach to Understanding Viral Hemorrhagic Fever Pathogenesis.' We report progress in five key areas: single cell isolation devices and control systems, fluorescent cytokine and transcription factor reporters, on-chip viral infection assays, molecular virology analysis of Arenavirus nucleoprotein structure-function, and development of computational tools to predict virus-host protein interactions. Although a great deal of work remains from that begun here, we have developed several novel single cell analysis tools and knowledge of Arenavirus biology that will facilitate and inform future publications and funding proposals.

Organizing for low cost space transportation

NASA Technical Reports Server (NTRS)

Lee, C. M.

1977-01-01

The paper describes the management concepts and organizational structure NASA is establishing to operate the Space Transportation System. Policies which would encourage public and commercial organizations and private individuals to use the new STS are discussed, and design criteria for experiments, spacecraft, and other systems elements are considered. The design criteria are intented to facilitate cost reductions for space operations. NASA plans for the transition from currently used expendable launch vehicles to Shuttle use and Shuttle pricing policies are explained in detail. Hardware development is basically complete, management functions have been defined, pricing policies have been published, and procedures for user contact and services have been places into operation.

MODEST: A Tool for Geodesy and Astronomy

NASA Technical Reports Server (NTRS)

Sovers, Ojars J.; Jacobs, Christopher S.; Lanyi, Gabor E.

2004-01-01

Features of the JPL VLBI modeling and estimation software "MODEST" are reviewed. Its main advantages include thoroughly documented model physics, portability, and detailed error modeling. Two unique models are included: modeling of source structure and modeling of both spatial and temporal correlations in tropospheric delay noise. History of the code parallels the development of the astrometric and geodetic VLBI technique and the software retains many of the models implemented during its advancement. The code has been traceably maintained since the early 1980s, and will continue to be updated with recent IERS standards. Scripts are being developed to facilitate user-friendly data processing in the era of e-VLBI.

Experimental and theoretical determination of σ bands on ("2 √{3 }×2 √{3 } ") silicene grown on Ag(111)

NASA Astrophysics Data System (ADS)

Wang, W.; Olovsson, W.; Uhrberg, R. I. G.

2015-11-01

Silicene, the two-dimensional (2D) allotrope of silicon, has very recently attracted a lot of attention. It has a structure that is similar to graphene and it is theoretically predicted to show the same kind of electronic properties which have put graphene into the focus of large research and development projects worldwide. In particular, a 2D structure made from Si is of high interest because of the application potential in Si-based electronic devices. However, so far there is not much known about the silicene band structure from experimental studies. A comprehensive study is here presented of the atomic and electronic structure of the silicene phase on Ag(111) denoted as (2 √ 3 ×2 √ 3 )R30° in the literature. Low energy electron diffraction (LEED) shows an unconventional rotated ("2 √ 3 ×2 √ 3 ") pattern with a complicated set of split diffraction spots. Scanning tunneling microscopy (STM) results reveal a Ag(111) surface that is homogeneously covered by the ("2 √ 3 ×2 √ 3 ") silicene which exhibits an additional quasiperiodic long-range ordered superstructure. The complex structure, revealed by STM, has been investigated in detail and we present a consistent picture of the silicene structure based on both STM and LEED. The homogeneous coverage by the ("2 √ 3 ×2 √ 3 ") silicene facilitated an angle-resolved photoelectron spectroscopy study which reveals a silicene band structure of unprecedented detail. Here we report four silicene bands which are compared to calculated dispersions based on a relaxed (2 √ 3 ×2 √ 3 ) model. We find good qualitative agreement between the experimentally observed bands and calculated silicene bands of σ character.

Can biochemistry drive drug discovery beyond simple potency measurements?

PubMed

Chène, Patrick

2012-04-01

Among the fields of expertise required to develop drugs successfully, biochemistry holds a key position in drug discovery at the interface between chemistry, structural biology and cell biology. However, taking the example of protein kinases, it appears that biochemical assays are mostly used in the pharmaceutical industry to measure compound potency and/or selectivity. This limited use of biochemistry is surprising, given that detailed biochemical analyses are commonly used in academia to unravel molecular recognition processes. In this article, I show that biochemistry can provide invaluable information on the dynamics and energetics of compound-target interactions that cannot be obtained on the basis of potency measurements and structural data. Therefore, an extensive use of biochemistry in drug discovery could facilitate the identification and/or development of new drugs. Copyright © 2012 Elsevier Ltd. All rights reserved.

Space Generic Open Avionics Architecture (SGOAA) standard specification

NASA Technical Reports Server (NTRS)

Wray, Richard B.; Stovall, John R.

1994-01-01

This standard establishes the Space Generic Open Avionics Architecture (SGOAA). The SGOAA includes a generic functional model, processing structural model, and an architecture interface model. This standard defines the requirements for applying these models to the development of spacecraft core avionics systems. The purpose of this standard is to provide an umbrella set of requirements for applying the generic architecture models to the design of a specific avionics hardware/software processing system. This standard defines a generic set of system interface points to facilitate identification of critical services and interfaces. It establishes the requirement for applying appropriate low level detailed implementation standards to those interfaces points. The generic core avionics functions and processing structural models provided herein are robustly tailorable to specific system applications and provide a platform upon which the interface model is to be applied.

3D radar wavefield tomography of comet interiors

NASA Astrophysics Data System (ADS)

Sava, Paul; Asphaug, Erik

2018-04-01

Answering fundamental questions about the origin and evolution of small planetary bodies hinges on our ability to image their surface and interior structure in detail and at high resolution. The interior structure is not easily accessible without systematic imaging using, e.g., radar transmission and reflection data from multiple viewpoints, as in medical tomography. Radar tomography can be performed using methodology adapted from terrestrial exploration seismology. Our feasibility study primarily focuses on full wavefield methods that facilitate high quality imaging of small body interiors. We consider the case of a monostatic system (co-located transmitters and receivers) operated in various frequency bands between 5 and 15 MHz, from a spacecraft in slow polar orbit around a spinning comet nucleus. Using realistic numerical experiments, we demonstrate that wavefield techniques can generate high resolution tomograms of comets nuclei with arbitrary shape and complex interior properties.

Toward the automated analysis of plasma physics problems

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

Mynick, H.E.

1989-04-01

A program (CALC) is described, which carries out nontrivial plasma physics calculations, in a manner intended to emulate the approach of a human theorist. This includes the initial process of gathering the relevant equations from a plasma knowledge base, and then determining how to solve them. Solution of the sets of equations governing physics problems, which in general have a nonuniform,irregular structure, not amenable to solution by standardized algorithmic procedures, is facilitated by an analysis of the structure of the equations and the relations among them. This often permits decompositions of the full problem into subproblems, and other simplifications inmore » form, which renders the resultant subsystems soluble by more standardized tools. CALC's operation is illustrated by a detailed description of its treatment of a sample plasma calculation. 5 refs., 3 figs.« less

Facilitation of Mourning During Childhood.

ERIC Educational Resources Information Center

Kliman, Gilbert; And Others

This paper discusses case studies of children psychologically disturbed by the death of parents or siblings. Illustrations of mourning facilitation were mainly gathered from 16 orphaned children, ages 3-14. Some techniques used in helping children mourn include: discussing physical details of the illness, discussing previous deaths of animals and…

Style grammars for interactive visualization of architecture.

PubMed

Aliaga, Daniel G; Rosen, Paul A; Bekins, Daniel R

2007-01-01

Interactive visualization of architecture provides a way to quickly visualize existing or novel buildings and structures. Such applications require both fast rendering and an effortless input regimen for creating and changing architecture using high-level editing operations that automatically fill in the necessary details. Procedural modeling and synthesis is a powerful paradigm that yields high data amplification and can be coupled with fast-rendering techniques to quickly generate plausible details of a scene without much or any user interaction. Previously, forward generating procedural methods have been proposed where a procedure is explicitly created to generate particular content. In this paper, we present our work in inverse procedural modeling of buildings and describe how to use an extracted repertoire of building grammars to facilitate the visualization and quick modification of architectural structures and buildings. We demonstrate an interactive application where the user draws simple building blocks and, using our system, can automatically complete the building "in the style of" other buildings using view-dependent texture mapping or nonphotorealistic rendering techniques. Our system supports an arbitrary number of building grammars created from user subdivided building models and captured photographs. Using only edit, copy, and paste metaphors, the entire building styles can be altered and transferred from one building to another in a few operations, enhancing the ability to modify an existing architectural structure or to visualize a novel building in the style of the others.

Genetic Structures of Copy Number Variants Revealed by Genotyping Single Sperm

PubMed Central

Luo, Minjie; Cui, Xiangfeng; Fredman, David; Brookes, Anthony J.; Azaro, Marco A.; Greenawalt, Danielle M.; Hu, Guohong; Wang, Hui-Yun; Tereshchenko, Irina V.; Lin, Yong; Shentu, Yue; Gao, Richeng; Shen, Li; Li, Honghua

2009-01-01

Background Copy number variants (CNVs) occupy a significant portion of the human genome and may have important roles in meiotic recombination, human genome evolution and gene expression. Many genetic diseases may be underlain by CNVs. However, because of the presence of their multiple copies, variability in copy numbers and the diploidy of the human genome, detailed genetic structure of CNVs cannot be readily studied by available techniques. Methodology/Principal Findings Single sperm samples were used as the primary subjects for the study so that CNV haplotypes in the sperm donors could be studied individually. Forty-eight CNVs characterized in a previous study were analyzed using a microarray-based high-throughput genotyping method after multiplex amplification. Seventeen single nucleotide polymorphisms (SNPs) were also included as controls. Two single-base variants, either allelic or paralogous, could be discriminated for all markers. Microarray data were used to resolve SNP alleles and CNV haplotypes, to quantitatively assess the numbers and compositions of the paralogous segments in each CNV haplotype. Conclusions/Significance This is the first study of the genetic structure of CNVs on a large scale. Resulting information may help understand evolution of the human genome, gain insight into many genetic processes, and discriminate between CNVs and SNPs. The highly sensitive high-throughput experimental system with haploid sperm samples as subjects may be used to facilitate detailed large-scale CNV analysis. PMID:19384415

Structural insights into binding of inhibitors to soluble epoxide hydrolase gained by fragment screening and X-ray crystallography.

PubMed

Amano, Yasushi; Yamaguchi, Tomohiko; Tanabe, Eiki

2014-04-15

Soluble epoxide hydrolase (sEH) is a component of the arachidonic acid cascade and is a candidate target for therapies for hypertension or inflammation. Although many sEH inhibitors are available, their scaffolds are not structurally diverse, and knowledge of their specific interactions with sEH is limited. To obtain detailed structural information about protein-ligand interactions, we conducted fragment screening of sEH, analyzed the fragments using high-throughput X-ray crystallography, and determined 126 fragment-bound structures at high resolution. Aminothiazole and benzimidazole derivatives were identified as novel scaffolds that bind to the catalytic triad of sEH with good ligand efficiency. We further identified fragment hits that bound to subpockets of sEH called the short and long branches. The water molecule conserved in the structure plays an important role in binding to the long branch, whereas Asp496 and the main chain of Phe497 form hydrogen bonds with fragment hits in the short branch. Fragment hits and their crystal structures provide structural insights into ligand binding to sEH that will facilitate the discovery of novel and potent inhibitors of sEH. Copyright © 2014 Elsevier Ltd. All rights reserved.

Structural hierarchy in molecular films of two class II hydrophobins.

PubMed

Paananen, Arja; Vuorimaa, Elina; Torkkeli, Mika; Penttilä, Merja; Kauranen, Martti; Ikkala, Olli; Lemmetyinen, Helge; Serimaa, Ritva; Linder, Markus B

2003-05-13

Hydrophobins are highly surface-active proteins that are specific to filamentous fungi. They function as coatings on various fungal structures, enable aerial growth of hyphae, and facilitate attachment to surfaces. Little is known about their structures and structure-function relationships. In this work we show highly organized surface layers of hydrophobins, representing the most detailed structural study of hydrophobin films so far. Langmuir-Blodgett films of class II hydrophobins HFBI and HFBII from Trichoderma reesei were prepared and analyzed by atomic force microscopy. The films showed highly ordered two-dimensional crystalline structures. By combining our recent results on small-angle X-ray scattering of hydrophobin solutions, we found that the unit cells in the films have dimensions similar to those of tetrameric aggregates found in solutions. Further analysis leads to a model in which the building blocks of the two-dimensional crystals are shape-persistent supramolecules consisting of four hydrophobin molecules. The results also indicate functional and structural differences between HFBI and HFBII that help to explain differences in their properties. The possibility that the highly organized surface assemblies of hydrophobins could allow a route for manufacturing functional surfaces is suggested.

Concerted ligand exchange and the roles of counter anions in the reversible structural switching of crystalline peptide metallo-macrocycles.

PubMed

Miyake, Ryosuke; Shionoya, Mitsuhiko

2014-06-02

To understand reversible structural switching in crystalline materials, we studied the mechanism of reversible crystal-to-crystal transformation of a tetranuclear Ni(II) macrocycle consisting of artificial β-dipeptides. On the basis of detailed structural analyses and thermodynamic measurements made in a comparison of pseudo-isostructural crystals (NO3 and BF4 salts), we herein discuss how ligand-exchange reactions take place in the crystal due to changes in water content and temperature. Observations of the structural transformation of NO3 salt indicated that a pseudo crystalline phase transformation takes place through concerted ligand-exchange reactions at the four Ni(II) centers of the macrocycle with hydrogen bond switching. A mechanism for this ligand exchange was supported by IR spectroscopy. Thermodynamic measurements suggested that the favorable compensation relationship of the enthalpy changes due to water uptake and structural changes are keys to the reversible structural transformation. On the basis of a comparison with the pseudo-isostructural crystals, it is apparent that the crystal packing structure and the types of counter anions are important factors for facilitating reversible ligand exchange with single crystallinity.

Barriers to and facilitators of implementing complex workplace dietary interventions: process evaluation results of a cluster controlled trial.

PubMed

Fitzgerald, Sarah; Geaney, Fiona; Kelly, Clare; McHugh, Sheena; Perry, Ivan J

2016-04-21

Ambiguity exists regarding the effectiveness of workplace dietary interventions. Rigorous process evaluation is vital to understand this uncertainty. This study was conducted as part of the Food Choice at Work trial which assessed the comparative effectiveness of a workplace environmental dietary modification intervention and an educational intervention both alone and in combination versus a control workplace. Effectiveness was assessed in terms of employees' dietary intakes, nutrition knowledge and health status in four large manufacturing workplaces. The study aimed to examine barriers to and facilitators of implementing complex workplace interventions, from the perspectives of key workplace stakeholders and researchers involved in implementation. A detailed process evaluation monitored and evaluated intervention implementation. Interviews were conducted at baseline (27 interviews) and at 7-9 month follow-up (27 interviews) with a purposive sample of workplace stakeholders (managers and participating employees). Topic guides explored factors which facilitated or impeded implementation. Researchers involved in recruitment and data collection participated in focus groups at baseline and at 7-9 month follow-up to explore their perceptions of intervention implementation. Data were imported into NVivo software and analysed using a thematic framework approach. Four major themes emerged; perceived benefits of participation, negotiation and flexibility of the implementation team, viability and intensity of interventions and workplace structures and cultures. The latter three themes either positively or negatively affected implementation, depending on context. The implementation team included managers involved in coordinating and delivering the interventions and the researchers who collected data and delivered intervention elements. Stakeholders' perceptions of the benefits of participating, which facilitated implementation, included managers' desire to improve company image and employees seeking health improvements. Other facilitators included stakeholder buy-in, organisational support and stakeholder cohesiveness with regards to the level of support provided to the intervention. Anticipation of employee resistance towards menu changes, workplace restructuring and target-driven workplace cultures impeded intervention implementation. Contextual factors such as workplace structures and cultures need to be considered in the implementation of future workplace dietary interventions. Negotiation and flexibility of key workplace stakeholders plays an integral role in overcoming the barriers of workplace cultures, structures and resistance to change. Current Controlled Trials: ISRCTN35108237. Date of registration: 02/07/2013.

Composite Action in Prestressed NU I-Girder Bridge Deck Systems Constructed with Bond Breakers to Facilitate Deck Removal

DOT National Transportation Integrated Search

2017-11-01

Results are reported from tests of small-scale push-off and large-scale composite NU I-girder specimens conducted to establish an interface connection detail that (1) Facilitates in-situ removal of the bridge deck without damaging prestressed girders...

Composite Action in Prestressed NU I-Girder Bridge Deck Systems Constructed with Bond Breakers to Facilitate Deck Removal : Technical Summary

DOT National Transportation Integrated Search

2017-11-01

Results are reported from tests of small-scale push-off and large-scale composite NU I-girder specimens conducted to establish an interface connection detail that (1) Facilitates in-situ removal of the bridge deck without damaging prestressed girders...

DrugBank 4.0: shedding new light on drug metabolism

PubMed Central

Law, Vivian; Knox, Craig; Djoumbou, Yannick; Jewison, Tim; Guo, An Chi; Liu, Yifeng; Maciejewski, Adam; Arndt, David; Wilson, Michael; Neveu, Vanessa; Tang, Alexandra; Gabriel, Geraldine; Ly, Carol; Adamjee, Sakina; Dame, Zerihun T.; Han, Beomsoo; Zhou, You; Wishart, David S.

2014-01-01

DrugBank (http://www.drugbank.ca) is a comprehensive online database containing extensive biochemical and pharmacological information about drugs, their mechanisms and their targets. Since it was first described in 2006, DrugBank has rapidly evolved, both in response to user requests and in response to changing trends in drug research and development. Previous versions of DrugBank have been widely used to facilitate drug and in silico drug target discovery. The latest update, DrugBank 4.0, has been further expanded to contain data on drug metabolism, absorption, distribution, metabolism, excretion and toxicity (ADMET) and other kinds of quantitative structure activity relationships (QSAR) information. These enhancements are intended to facilitate research in xenobiotic metabolism (both prediction and characterization), pharmacokinetics, pharmacodynamics and drug design/discovery. For this release, >1200 drug metabolites (including their structures, names, activity, abundance and other detailed data) have been added along with >1300 drug metabolism reactions (including metabolizing enzymes and reaction types) and dozens of drug metabolism pathways. Another 30 predicted or measured ADMET parameters have been added to each DrugCard, bringing the average number of quantitative ADMET values for Food and Drug Administration-approved drugs close to 40. Referential nuclear magnetic resonance and MS spectra have been added for almost 400 drugs as well as spectral and mass matching tools to facilitate compound identification. This expanded collection of drug information is complemented by a number of new or improved search tools, including one that provides a simple analyses of drug–target, –enzyme and –transporter associations to provide insight on drug–drug interactions. PMID:24203711

DrugBank 4.0: shedding new light on drug metabolism.

PubMed

Law, Vivian; Knox, Craig; Djoumbou, Yannick; Jewison, Tim; Guo, An Chi; Liu, Yifeng; Maciejewski, Adam; Arndt, David; Wilson, Michael; Neveu, Vanessa; Tang, Alexandra; Gabriel, Geraldine; Ly, Carol; Adamjee, Sakina; Dame, Zerihun T; Han, Beomsoo; Zhou, You; Wishart, David S

2014-01-01

DrugBank (http://www.drugbank.ca) is a comprehensive online database containing extensive biochemical and pharmacological information about drugs, their mechanisms and their targets. Since it was first described in 2006, DrugBank has rapidly evolved, both in response to user requests and in response to changing trends in drug research and development. Previous versions of DrugBank have been widely used to facilitate drug and in silico drug target discovery. The latest update, DrugBank 4.0, has been further expanded to contain data on drug metabolism, absorption, distribution, metabolism, excretion and toxicity (ADMET) and other kinds of quantitative structure activity relationships (QSAR) information. These enhancements are intended to facilitate research in xenobiotic metabolism (both prediction and characterization), pharmacokinetics, pharmacodynamics and drug design/discovery. For this release, >1200 drug metabolites (including their structures, names, activity, abundance and other detailed data) have been added along with >1300 drug metabolism reactions (including metabolizing enzymes and reaction types) and dozens of drug metabolism pathways. Another 30 predicted or measured ADMET parameters have been added to each DrugCard, bringing the average number of quantitative ADMET values for Food and Drug Administration-approved drugs close to 40. Referential nuclear magnetic resonance and MS spectra have been added for almost 400 drugs as well as spectral and mass matching tools to facilitate compound identification. This expanded collection of drug information is complemented by a number of new or improved search tools, including one that provides a simple analyses of drug-target, -enzyme and -transporter associations to provide insight on drug-drug interactions.

BclxL changes conformation upon binding to wild-type but not mutant p53 DNA binding domain.

PubMed

Hagn, Franz; Klein, Christian; Demmer, Oliver; Marchenko, Natasha; Vaseva, Angelina; Moll, Ute M; Kessler, Horst

2010-01-29

p53 can induce apoptosis through mitochondrial membrane permeabilization by interaction of its DNA binding region with the anti-apoptotic proteins BclxL and Bcl2. However, little is known about the action of p53 at the mitochondria in molecular detail. By using NMR spectroscopy and fluorescence polarization we characterized the binding of wild-type and mutant p53 DNA binding domains to BclxL and show that the wild-type p53 DNA binding domain leads to structural changes in the BH3 binding region of BclxL, whereas mutants fail to induce such effects due to reduced affinity. This was probed by induced chemical shift and residual dipolar coupling data. These data imply that p53 partly achieves its pro-apoptotic function at the mitochondria by facilitating interaction between BclxL and BH3-only proteins in an allosteric mode of action. Furthermore, we characterize for the first time the binding behavior of Pifithrin-mu, a specific small molecule inhibitor of the p53-BclxL interaction, and present a structural model of the protein-ligand complex. A rather unusual behavior is revealed whereby Pifithrin-mu binds to both sides of the protein-protein complex. These data should facilitate the rational design of more potent specific BclxL-p53 inhibitors.

Standardizing Naming Conventions in Radiation Oncology

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

Santanam, Lakshmi; Hurkmans, Coen; Mutic, Sasa

2012-07-15

Purpose: The aim of this study was to report on the development of a standardized target and organ-at-risk naming convention for use in radiation therapy and to present the nomenclature for structure naming for interinstitutional data sharing, clinical trial repositories, integrated multi-institutional collaborative databases, and quality control centers. This taxonomy should also enable improved plan benchmarking between clinical institutions and vendors and facilitation of automated treatment plan quality control. Materials and Methods: The Advanced Technology Consortium, Washington University in St. Louis, Radiation Therapy Oncology Group, Dutch Radiation Oncology Society, and the Clinical Trials RT QA Harmonization Group collaborated in creatingmore » this new naming convention. The International Commission on Radiation Units and Measurements guidelines have been used to create standardized nomenclature for target volumes (clinical target volume, internal target volume, planning target volume, etc.), organs at risk, and planning organ-at-risk volumes in radiation therapy. The nomenclature also includes rules for specifying laterality and margins for various structures. The naming rules distinguish tumor and nodal planning target volumes, with correspondence to their respective tumor/nodal clinical target volumes. It also provides rules for basic structure naming, as well as an option for more detailed names. Names of nonstandard structures used mainly for plan optimization or evaluation (rings, islands of dose avoidance, islands where additional dose is needed [dose painting]) are identified separately. Results: In addition to its use in 16 ongoing Radiation Therapy Oncology Group advanced technology clinical trial protocols and several new European Organization for Research and Treatment of Cancer protocols, a pilot version of this naming convention has been evaluated using patient data sets with varying treatment sites. All structures in these data sets were satisfactorily identified using this nomenclature. Conclusions: Use of standardized naming conventions is important to facilitate comparison of dosimetry across patient datasets. The guidelines presented here will facilitate international acceptance across a wide range of efforts, including groups organizing clinical trials, Radiation Oncology Institute, Dutch Radiation Oncology Society, Integrating the Healthcare Enterprise, Radiation Oncology domain (IHE-RO), and Digital Imaging and Communication in Medicine (DICOM).« less

A single mutation in the castor Delta9-18:0-desaturase changes reaction partitioning from desaturation to oxidase chemistry.

PubMed

Guy, Jodie E; Abreu, Isabel A; Moche, Martin; Lindqvist, Ylva; Whittle, Edward; Shanklin, John

2006-11-14

Sequence analysis of the diiron cluster-containing soluble desaturases suggests they are unrelated to other diiron enzymes; however, structural alignment of the core four-helix bundle of desaturases to other diiron enzymes reveals a conserved iron binding motif with similar spacing in all enzymes of this structural class, implying a common evolutionary ancestry. Detailed structural comparison of the castor desaturase with that of a peroxidase, rubrerythrin, shows remarkable conservation of both identity and geometry of residues surrounding the diiron center, with the exception of residue 199. Position 199 is occupied by a threonine in the castor desaturase, but the equivalent position in rubrerythrin contains a glutamic acid. We previously hypothesized that a carboxylate in this location facilitates oxidase chemistry in rubrerythrin by the close apposition of a residue capable of facilitating proton transfer to the activated oxygen (in a hydrophobic cavity adjacent to the diiron center based on the crystal structure of the oxygen-binding mimic azide). Here we report that desaturase mutant T199D binds substrate but its desaturase activity decreases by approximately 2 x 10(3)-fold. However, it shows a >31-fold increase in peroxide-dependent oxidase activity with respect to WT desaturase, as monitored by single-turnover stopped-flow spectrometry. A 2.65-A crystal structure of T199D reveals active-site geometry remarkably similar to that of rubrerythrin, consistent with its enhanced function as an oxidase enzyme. That a single amino acid substitution can switch reactivity from desaturation to oxidation provides experimental support for the hypothesis that the desaturase evolved from an ancestral oxidase enzyme.

A single mutation in the castor Δ9-18:0-desaturase changes reaction partitioning from desaturation to oxidase chemistry

PubMed Central

Guy, Jodie E.; Abreu, Isabel A.; Moche, Martin; Lindqvist, Ylva; Whittle, Edward; Shanklin, John

2006-01-01

Sequence analysis of the diiron cluster-containing soluble desaturases suggests they are unrelated to other diiron enzymes; however, structural alignment of the core four-helix bundle of desaturases to other diiron enzymes reveals a conserved iron binding motif with similar spacing in all enzymes of this structural class, implying a common evolutionary ancestry. Detailed structural comparison of the castor desaturase with that of a peroxidase, rubrerythrin, shows remarkable conservation of both identity and geometry of residues surrounding the diiron center, with the exception of residue 199. Position 199 is occupied by a threonine in the castor desaturase, but the equivalent position in rubrerythrin contains a glutamic acid. We previously hypothesized that a carboxylate in this location facilitates oxidase chemistry in rubrerythrin by the close apposition of a residue capable of facilitating proton transfer to the activated oxygen (in a hydrophobic cavity adjacent to the diiron center based on the crystal structure of the oxygen-binding mimic azide). Here we report that desaturase mutant T199D binds substrate but its desaturase activity decreases by ≈2 × 103-fold. However, it shows a >31-fold increase in peroxide-dependent oxidase activity with respect to WT desaturase, as monitored by single-turnover stopped-flow spectrometry. A 2.65-Å crystal structure of T199D reveals active-site geometry remarkably similar to that of rubrerythrin, consistent with its enhanced function as an oxidase enzyme. That a single amino acid substitution can switch reactivity from desaturation to oxidation provides experimental support for the hypothesis that the desaturase evolved from an ancestral oxidase enzyme. PMID:17088542

Electrophysiological characterization of the archaeal transporter NCX_Mj using solid supported membrane technology

PubMed Central

Barthmes, Maria; Liao, Jun; Jiang, Youxing; Brüggemann, Andrea

2016-01-01

Sodium–calcium exchangers (NCXs) are membrane transporters that play an important role in Ca2+ homeostasis and Ca2+ signaling. The recent crystal structure of NCX_Mj, a member of the NCX family from the archaebacterium Methanococcus jannaschii, provided insight into the atomistic details of sodium–calcium exchange. Here, we extend these findings by providing detailed functional data on purified NCX_Mj using solid supported membrane (SSM)–based electrophysiology, a powerful but unexploited tool for functional studies of electrogenic transporter proteins. We show that NCX_Mj is highly selective for Na+, whereas Ca2+ can be replaced by Mg2+ and Sr2+ and that NCX_Mj can be inhibited by divalent ions, particularly Cd2+. By directly comparing the apparent affinities of Na+ and Ca2+ for NCX_Mj with those for human NCX1, we show excellent agreement, indicating a strong functional similarity between NCX_Mj and its eukaryotic isoforms. We also provide detailed instructions to facilitate the adaption of this method to other electrogenic transporter proteins. Our findings demonstrate that NCX_Mj can serve as a model for the NCX family and highlight several possible applications for SSM-based electrophysiology. PMID:27241699

The antigen 43 structure reveals a molecular Velcro-like mechanism of autotransporter-mediated bacterial clumping

PubMed Central

Heras, Begoña; Totsika, Makrina; Peters, Kate M.; Paxman, Jason J.; Gee, Christine L.; Jarrott, Russell J.; Perugini, Matthew A.; Whitten, Andrew E.; Schembri, Mark A.

2014-01-01

Aggregation and biofilm formation are critical mechanisms for bacterial resistance to host immune factors and antibiotics. Autotransporter (AT) proteins, which represent the largest group of outer-membrane and secreted proteins in Gram-negative bacteria, contribute significantly to these phenotypes. Despite their abundance and role in bacterial pathogenesis, most AT proteins have not been structurally characterized, and there is a paucity of detailed information with regard to their mode of action. Here we report the structure–function relationships of Antigen 43 (Ag43a), a prototypic self-associating AT protein from uropathogenic Escherichia coli. The functional domain of Ag43a displays a twisted L-shaped β-helical structure firmly stabilized by a 3D hydrogen-bonded scaffold. Notably, the distinctive Ag43a L shape facilitates self-association and cell aggregation. Combining all our data, we define a molecular “Velcro-like” mechanism of AT-mediated bacterial clumping, which can be tailored to fit different bacterial lifestyles such as the formation of biofilms. PMID:24335802

Glycan Remodeling with Processing Inhibitors and Lectin-Resistant Eukaryotic Cells.

PubMed

Chang, Veronica T; Spooner, Robert A; Crispin, Max; Davis, Simon J

2015-01-01

Some of the most important and interesting molecules in metazoan biology are glycoproteins. The importance of the carbohydrate component of these structures is often revealed by the disease phenotypes that manifest when the biosynthesis of particular glycoforms is disrupted. On the other hand, the presence of large amounts of carbohydrate can often hinder the structural and functional analysis of glycoproteins. There are often good reasons, therefore, for wanting to engineer and predefine the N-glycans present on glycoproteins, e.g., in order to characterize the functions of the glycans or facilitate their subsequent removal. Here, we describe in detail two distinct ways in which to usefully interfere with oligosaccharide processing, one involving the use of specific processing inhibitors, and the other the selection of cell lines mutated at gene loci that control oligosaccharide processing, using cytotoxic lectins. Both approaches have the capacity for controlled, radical alteration of oligosaccharide processing in eukaryotic cells used for heterologous protein expression, and have great utility in the structural analysis of glycoproteins.

Approaches to the structural modelling of insect wings.

PubMed Central

Wootton, R J; Herbert, R C; Young, P G; Evans, K E

2003-01-01

Insect wings lack internal muscles, and the orderly, necessary deformations which they undergo in flight and folding are in part remotely controlled, in part encoded in their structure. This factor is crucial in understanding their complex, extremely varied morphology. Models have proved particularly useful in clarifying the facilitation and control of wing deformation. Their development has followed a logical sequence from conceptual models through physical and simple analytical to numerical models. All have value provided their limitations are realized and constant comparisons made with the properties and mechanical behaviour of real wings. Numerical modelling by the finite element method is by far the most time-consuming approach, but has real potential in analysing the adaptive significance of structural details and interpreting evolutionary trends. Published examples are used to review the strengths and weaknesses of each category of model, and a summary is given of new work using finite element modelling to investigate the vibration properties and response to impact of hawkmoth wings. PMID:14561349

Solar assisted alkali pretreatment of garden biomass: Effects on lignocellulose degradation, enzymatic hydrolysis, crystallinity and ultra-structural changes in lignocellulose.

PubMed

Gabhane, Jagdish; William, S P M Prince; Vaidya, Atul N; Das, Sera; Wate, Satish R

2015-06-01

A comprehensive study was carried out to assess the effectiveness of solar assisted alkali pretreatment (SAAP) on garden biomass (GB). The pretreatment efficiency was assessed based on lignocellulose degradation, conversion of cellulose into reducing sugars, changes in the ultra-structure and functional groups of lignocellulose and impact on the crystallinity of cellulose, etc. SAAP was found to be efficient for the removal of lignin and hemicellulose that facilitated enzymatic hydrolysis of cellulose. FTIR and XRD studies provided details on the effectiveness of SAAP on lignocellulosic moiety and crystallinity of cellulose. Scanning electron microscopic analysis showed ultra-structural disturbances in the microfibrils of GB as a result of pretreatment. The mass balance closer of 97.87% after pretreatment confirmed the reliability of SAAP pretreatment. Based on the results, it is concluded that SAAP is not only an efficient means of pretreatment but also economical as it involved no energy expenditure for heat generation during pretreatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

RaptorX-Angle: real-value prediction of protein backbone dihedral angles through a hybrid method of clustering and deep learning.

PubMed

Gao, Yujuan; Wang, Sheng; Deng, Minghua; Xu, Jinbo

2018-05-08

Protein dihedral angles provide a detailed description of protein local conformation. Predicted dihedral angles can be used to narrow down the conformational space of the whole polypeptide chain significantly, thus aiding protein tertiary structure prediction. However, direct angle prediction from sequence alone is challenging. In this article, we present a novel method (named RaptorX-Angle) to predict real-valued angles by combining clustering and deep learning. Tested on a subset of PDB25 and the targets in the latest two Critical Assessment of protein Structure Prediction (CASP), our method outperforms the existing state-of-art method SPIDER2 in terms of Pearson Correlation Coefficient (PCC) and Mean Absolute Error (MAE). Our result also shows approximately linear relationship between the real prediction errors and our estimated bounds. That is, the real prediction error can be well approximated by our estimated bounds. Our study provides an alternative and more accurate prediction of dihedral angles, which may facilitate protein structure prediction and functional study.

[Hybrid 3-D rendering of the thorax and surface-based virtual bronchoscopy in surgical and interventional therapy control].

PubMed

Seemann, M D; Gebicke, K; Luboldt, W; Albes, J M; Vollmar, J; Schäfer, J F; Beinert, T; Englmeier, K H; Bitzer, M; Claussen, C D

2001-07-01

The aim of this study was to demonstrate the possibilities of a hybrid rendering method, the combination of a color-coded surface and volume rendering method, with the feasibility of performing surface-based virtual endoscopy with different representation models in the operative and interventional therapy control of the chest. In 6 consecutive patients with partial lung resection (n = 2) and lung transplantation (n = 4) a thin-section spiral computed tomography of the chest was performed. The tracheobronchial system and the introduced metallic stents were visualized using a color-coded surface rendering method. The remaining thoracic structures were visualized using a volume rendering method. For virtual bronchoscopy, the tracheobronchial system was visualized using a triangle surface model, a shaded-surface model and a transparent shaded-surface model. The hybrid 3D visualization uses the advantages of both the color-coded surface and volume rendering methods and facilitates a clear representation of the tracheobronchial system and the complex topographical relationship of morphological and pathological changes without loss of diagnostic information. Performing virtual bronchoscopy with the transparent shaded-surface model facilitates a reasonable to optimal, simultaneous visualization and assessment of the surface structure of the tracheobronchial system and the surrounding mediastinal structures and lesions. Hybrid rendering relieve the morphological assessment of anatomical and pathological changes without the need for time-consuming detailed analysis and presentation of source images. Performing virtual bronchoscopy with a transparent shaded-surface model offers a promising alternative to flexible fiberoptic bronchoscopy.

Effects of lignin structure on hydrodeoxygenation reactivity of pine wood lignin to valuable chemicals

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

Wang, Hongliang; Ben, Haoxi; Southeast Univ., Nanjing

Hydrodeoxygenation (HDO) of two dilute acid flow through pretreated softwood lignin samples, including residual lignin in pretreated solid residues (ReL) and recovered insoluble lignin in pretreated liquid (RISL), with apparent different physical and chemical structures, was comprehensively studied. A combination of catalysts (HY zeolite and Ru/Al 2O 3) was employed to investigate the effects of lignin structures, especially condensed structures, on the HDO upgrading process. Results indicated that the condensed structure and short side chains in lignin hindered its HDO conversion under different reaction conditions, including catalyst loading and composition, hydrogen pressure, and reaction time. In addition to lignin structure,more » HY zeolite was found crucial for lignin depolymerization, while Ru/Al 2O 3 and relatively high hydrogen pressure (4 MPa) were necessary for upgrading unstable oxy-compounds to cyclohexanes at high selectivity (>95 wt %). Since the lignin structure essentially affects its reactivity during HDO conversion, the yield and selectivity of HDO products can be predicted by detailed characterization of the lignin structure. Furthermore, the insights gained from this study in the fundamental reaction mechanisms based on the lignin structure will facilitate upgrading of lignin to high-value products for applications in the production of both fuels and chemicals.« less

Effects of lignin structure on hydrodeoxygenation reactivity of pine wood lignin to valuable chemicals

DOE PAGES

Wang, Hongliang; Ben, Haoxi; Southeast Univ., Nanjing; ...

2017-01-05

Hydrodeoxygenation (HDO) of two dilute acid flow through pretreated softwood lignin samples, including residual lignin in pretreated solid residues (ReL) and recovered insoluble lignin in pretreated liquid (RISL), with apparent different physical and chemical structures, was comprehensively studied. A combination of catalysts (HY zeolite and Ru/Al 2O 3) was employed to investigate the effects of lignin structures, especially condensed structures, on the HDO upgrading process. Results indicated that the condensed structure and short side chains in lignin hindered its HDO conversion under different reaction conditions, including catalyst loading and composition, hydrogen pressure, and reaction time. In addition to lignin structure,more » HY zeolite was found crucial for lignin depolymerization, while Ru/Al 2O 3 and relatively high hydrogen pressure (4 MPa) were necessary for upgrading unstable oxy-compounds to cyclohexanes at high selectivity (>95 wt %). Since the lignin structure essentially affects its reactivity during HDO conversion, the yield and selectivity of HDO products can be predicted by detailed characterization of the lignin structure. Furthermore, the insights gained from this study in the fundamental reaction mechanisms based on the lignin structure will facilitate upgrading of lignin to high-value products for applications in the production of both fuels and chemicals.« less

The emerging physiological roles of the SLC14A family of urea transporters

PubMed Central

Stewart, Gavin

2011-01-01

In mammals, urea is the main nitrogenous breakdown product of protein catabolism and is produced in the liver. In certain tissues, the movement of urea across cell membranes is specifically mediated by a group of proteins known as the SLC14A family of facilitative urea transporters. These proteins are derived from two distinct genes, UT-A (SLC14A2) and UT-B (SLC14A1). Facilitative urea transporters play an important role in two major physiological processes – urinary concentration and urea nitrogen salvaging. Although UT-A and UT-B transporters both have a similar basic structure and mediate the transport of urea in a facilitative manner, there are a number of significant differences between them. UT-A transporters are mainly found in the kidney, are highly specific for urea, have relatively lower transport rates and are highly regulated at both gene expression and cellular localization levels. In contrast, UT-B transporters are more widespread in their tissue location, transport both urea and water, have a relatively high transport rate, are inhibited by mercurial compounds and currently appear to be less acutely regulated. This review details the fundamental research that has so far been performed to investigate the function and physiological significance of these two types of urea transporters. PMID:21449978

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

Slade, Daniel J.; Fang, Pengfei; Dreyton, Christina J.

Protein arginine deiminases (PADs) are calcium-dependent histone-modifying enzymes whose activity is dysregulated in inflammatory diseases and cancer. PAD2 functions as an Estrogen Receptor (ER) coactivator in breast cancer cells via the citrullination of histone tail arginine residues at ER binding sites. Although an attractive therapeutic target, the mechanisms that regulate PAD2 activity are largely unknown, especially the detailed role of how calcium facilitates enzyme activation. To gain insights into these regulatory processes, we determined the first structures of PAD2 (27 in total), and through calcium-titrations by X-ray crystallography, determined the order of binding and affinity for the six calcium ionsmore » that bind and activate this enzyme. These structures also identified several PAD2 regulatory elements, including a calcium switch that controls proper positioning of the catalytic cysteine residue, and a novel active site shielding mechanism. Additional biochemical and mass-spectrometry-based hydrogen/deuterium exchange studies support these structural findings. The identification of multiple intermediate calcium-bound structures along the PAD2 activation pathway provides critical insights that will aid the development of allosteric inhibitors targeting the PADs.« less

Structure of the TRPV1 ion channel determined by electron cryo-microscopy.

PubMed

Liao, Maofu; Cao, Erhu; Julius, David; Cheng, Yifan

2013-12-05

Transient receptor potential (TRP) channels are sensors for a wide range of cellular and environmental signals, but elucidating how these channels respond to physical and chemical stimuli has been hampered by a lack of detailed structural information. Here we exploit advances in electron cryo-microscopy to determine the structure of a mammalian TRP channel, TRPV1, at 3.4 Å resolution, breaking the side-chain resolution barrier for membrane proteins without crystallization. Like voltage-gated channels, TRPV1 exhibits four-fold symmetry around a central ion pathway formed by transmembrane segments 5-6 (S5-S6) and the intervening pore loop, which is flanked by S1-S4 voltage-sensor-like domains. TRPV1 has a wide extracellular 'mouth' with a short selectivity filter. The conserved 'TRP domain' interacts with the S4-S5 linker, consistent with its contribution to allosteric modulation. Subunit organization is facilitated by interactions among cytoplasmic domains, including amino-terminal ankyrin repeats. These observations provide a structural blueprint for understanding unique aspects of TRP channel function.

A facile chemical conversion synthesis of Sb2S3 nanotubes and the visible light-driven photocatalytic activities

PubMed Central

2012-01-01

We report a simple chemical conversion and cation exchange technique to realize the synthesis of Sb2S3 nanotubes at a low temperature of 90°C. The successful chemical conversion from ZnS nanotubes to Sb2S3 ones benefits from the large difference in solubility between ZnS and Sb2S3. The as-grown Sb2S3 nanotubes have been transformed from a weak crystallization to a polycrystalline structure via successive annealing. In addition to the detailed structural, morphological, and optical investigation of the yielded Sb2S3 nanotubes before and after annealing, we have shown high photocatalytic activities of Sb2S3 nanotubes for methyl orange degradation under visible light irradiation. This approach offers an effective control of the composition and structure of Sb2S3 nanomaterials, facilitates the production at a relatively low reaction temperature without the need of organics, templates, or crystal seeds, and can be extended to the synthesis of hollow structures with various compositions and shapes for unique properties. PMID:22448960

Structure and substrate ion binding in the sodium/proton antiporter PaNhaP

PubMed Central

Wöhlert, David; Kühlbrandt, Werner; Yildiz, Özkan

2014-01-01

Sodium/proton antiporters maintain intracellular pH and sodium levels. Detailed structures of antiporters with bound substrate ions are essential for understanding how they work. We have resolved the substrate ion in the dimeric, electroneutral sodium/proton antiporter PaNhaP from Pyrococcus abyssi at 3.2 Å, and have determined its structure in two different conformations at pH 8 and pH 4. The ion is coordinated by three acidic sidechains, a water molecule, a serine and a main-chain carbonyl in the unwound stretch of trans-membrane helix 5 at the deepest point of a negatively charged cytoplasmic funnel. A second narrow polar channel may facilitate proton uptake from the cytoplasm. Transport activity of PaNhaP is cooperative at pH 6 but not at pH 5. Cooperativity is due to pH-dependent allosteric coupling of protomers through two histidines at the dimer interface. Combined with comprehensive transport studies, the structures of PaNhaP offer unique new insights into the transport mechanism of sodium/proton antiporters. DOI: http://dx.doi.org/10.7554/eLife.03579.001 PMID:25426802

Structure of the TRPV1 ion channel determined by electron cryo-microscopy

PubMed Central

Liao, Maofu; Cao, Erhu; Julius, David; Cheng, Yifan

2014-01-01

Transient receptor potential (TRP) channels are sensors for a wide range of cellular and environmental signals, but elucidating how these channels respond to physical and chemical stimuli has been hampered by a lack of detailed structural information. Here, we exploit advances in electron cryo-microscopy to determine the structure of a mammalian TRP channel, TRPV1, at 3.4Å resolution, breaking the side-chain resolution barrier for membrane proteins without crystallization. Like voltage-gated channels, TRPV1 exhibits four-fold symmetry around a central ion pathway formed by transmembrane helices S5–S6 and the intervening pore loop, which is flanked by S1–S4 voltage sensor-like domains. TRPV1 has a wide extracellular ‘mouth’ with short selectivity filter. The conserved ‘TRP domain’ interacts with the S4–S5 linker, consistent with its contribution to allosteric modulation. Subunit organization is facilitated by interactions among cytoplasmic domains, including N-terminal ankyrin repeats. These observations provide a structural blueprint for understanding unique aspects of TRP channel function. PMID:24305160

Crystallization and preliminary crystallographic characterization of the origin-binding domain of the bacteriophage λ O replication initiator

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

Struble, E. B., E-mail: evi.struble@nist.gov; Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205; Center for Advanced Research in Biotechnology/NIST, 9600 Gudelsky Drive, Rockville, MD 20850

2007-06-01

Crystallization and preliminary diffraction data of the N-terminal 19–139 fragment of the origin-binding domain of bacteriophage λ O replication initiator are reported. The bacteriophage λ O protein binds to the λ replication origin (oriλ) and serves as the primary replication initiator for the viral genome. The binding energy derived from the binding of O to oriλ is thought to help drive DNA opening to facilitate initiation of DNA replication. Detailed understanding of this process is severely limited by the lack of high-resolution structures of O protein or of any lambdoid phage-encoded paralogs either with or without DNA. The production ofmore » crystals of the origin-binding domain of λ O that diffract to 2.5 Å is reported. Anomalous dispersion methods will be used to solve this structure.« less

Novel frontiers in ultra-structural and molecular MRI of the brain.

PubMed

Duyn, Jeff H; Koretsky, Alan P

2011-08-01

Recent developments in the MRI of the brain continue to expand its use in basic and clinical neuroscience. This review highlights some areas of recent progress. Higher magnetic field strengths and improved signal detectors have allowed improved visualization of the various properties of the brain, facilitating the anatomical definition of function-specific areas and their connections. For example, by sensitizing the MRI signal to the magnetic susceptibility of tissue, it is starting to become possible to reveal the laminar structure of the cortex and identify millimeter-scale fiber bundles. Using exogenous contrast agents, and innovative ways to manipulate contrast, it is becoming possible to highlight specific fiber tracts and cell populations. These techniques are bringing us closer to understanding the evolutionary blueprint of the brain, improving the detection and characterization of disease, and help to guide treatment. Recent MRI techniques are leading to more detailed and more specific contrast in the study of the brain.

Geology of the Devils Hole area, Nevada

USGS Publications Warehouse

Carr, W.J.

1988-01-01

Detailed and reconnaissance mapping of the Devils Hole, Nevada, area has improved definition of the local geologic structure within a regional carbonate aquifer near its primary discharge points -- the springs of Ash Meadows. Several formerly unmapped calcite veins, and other young calcite-lined paleo-spring feeder zones were found, as well as a number of previously unknown small collapse areas in the limestone. Although the predominant structural grain of the area is oriented northwest, the importance of the very subordinate northeast-striking faults and fractures is underscored by their association with Devils Hole itself, with most of the collapse depressions, and with many of the calcite veins in ' lake beds ' and alluvium. Probable channeling of groundwater flow may occur along one important northeast-striking fault zone. The persistent tendency for openings may have been facilitated by underlying low-angle faults that separate brittle carbonate rocks from underlying, less-competent clastic rocks. (Author 's abstract)

How disordered is my protein and what is its disorder for? A guide through the “dark side” of the protein universe

PubMed Central

Lieutaud, Philippe; Uversky, Alexey V.; Uversky, Vladimir N.; Longhi, Sonia

2016-01-01

ABSTRACT In the last 2 decades it has become increasingly evident that a large number of proteins are either fully or partially disordered. Intrinsically disordered proteins lack a stable 3D structure, are ubiquitous and fulfill essential biological functions. Their conformational heterogeneity is encoded in their amino acid sequences, thereby allowing intrinsically disordered proteins or regions to be recognized based on properties of these sequences. The identification of disordered regions facilitates the functional annotation of proteins and is instrumental for delineating boundaries of protein domains amenable to structural determination with X-ray crystallization. This article discusses a comprehensive selection of databases and methods currently employed to disseminate experimental and putative annotations of disorder, predict disorder and identify regions involved in induced folding. It also provides a set of detailed instructions that should be followed to perform computational analysis of disorder. PMID:28232901

Getting Things Sorted With Lagrangian Coherent Structures

NASA Astrophysics Data System (ADS)

Atis, Severine; Peacock, Thomas; Environmental Dynamics Laboratory Team

2014-11-01

The dispersion of a tracer in a fluid flow is influenced by the Lagrangian motion of fluid elements. Even in laminar regimes, the irregular chaotic behavior of a fluid flow can lead to effective stirring that rapidly redistributes a tracer throughout the domain. For flows with arbitrary time-dependence, the modern approach of Lagrangian Coherent Structures (LCSs) provide a method for identifying the key material lines that organize flow transport. When the advected tracer particles possess a finite size and nontrivial shape, however, their dynamics can differ markedly from passive tracers, thus affecting the dispersion phenomena. We present details of numerical simulations and laboratory experiments that investigate the behavior of finite size particles in 2-dimensional chaotic flows. We show that the shape and the size of the particles alter the underlying LCSs, facilitating segregation between tracers of different shape in the same flow field.

Artificial enzymes based on supramolecular scaffolds.

PubMed

Dong, Zeyuan; Luo, Quan; Liu, Junqiu

2012-12-07

Enzymes are nanometer-sized molecules with three-dimensional structures created by the folding and self-assembly of polymeric chain-like components through supramolecular interactions. They are capable of performing catalytic functions usually accompanied by a variety of conformational states. The conformational diversities and complexities of natural enzymes exerted in catalysis seriously restrict the detailed understanding of enzymatic mechanisms in molecular terms. A supramolecular viewpoint is undoubtedly helpful in understanding the principle of enzyme catalysis. The emergence of supramolecular artificial enzymes therefore provides an alternative way to approach the structural complexity and thus to unravel the mystery of enzyme catalysis. This critical review covers the recent development of artificial enzymes designed based on supramolecular scaffolds ranging from the synthetic macrocycles to self-assembled nanometer-sized objects. Such findings are anticipated to facilitate the design of supramolecular artificial enzymes as well as their potential uses in important fields, such as manufacturing and food industries, environmental biosensors, pharmaceutics and so on.

A case for ancient springs in Arabia Terra, Mars.

PubMed

Allen, Carlton C; Oehler, Dorothy Z

2008-12-01

Based on new image data from the High Resolution Imaging Science Experiment (HiRISE) on Mars Reconnaissance Orbiter (MRO), a case can be made that several structures in Vernal Crater, Arabia Terra are ancient springs. This interpretation is based on comprehensive geomorphologic analysis coupled with assessment of multiple hypotheses. The structures identified extend across several kilometers and are exceptional in that nothing with their detail and scale has been reported from Mars. The deposits are associated with an extensive fracture system that may have facilitated upward flow of warm fluids. Several additional spring-like features occur in Vernal Crater, and it is possible that these are part of a major province of spring activity. Since springs are environments where life could have evolved on Mars, where that life could have found refuge as the climate became colder and drier, and where signatures of that life may be preserved, Vernal Crater may be a site of major astrobiological importance.

Vectorization with SIMD extensions speeds up reconstruction in electron tomography.

PubMed

Agulleiro, J I; Garzón, E M; García, I; Fernández, J J

2010-06-01

Electron tomography allows structural studies of cellular structures at molecular detail. Large 3D reconstructions are needed to meet the resolution requirements. The processing time to compute these large volumes may be considerable and so, high performance computing techniques have been used traditionally. This work presents a vector approach to tomographic reconstruction that relies on the exploitation of the SIMD extensions available in modern processors in combination to other single processor optimization techniques. This approach succeeds in producing full resolution tomograms with an important reduction in processing time, as evaluated with the most common reconstruction algorithms, namely WBP and SIRT. The main advantage stems from the fact that this approach is to be run on standard computers without the need of specialized hardware, which facilitates the development, use and management of programs. Future trends in processor design open excellent opportunities for vector processing with processor's SIMD extensions in the field of 3D electron microscopy.

Revealing the synergetic effects in Ni nanoparticle-carbon nanotube hybrids by scanning transmission X-ray microscopy and their application in the hydrolysis of ammonia borane.

PubMed

Zhao, Guanqi; Zhong, Jun; Wang, Jian; Sham, Tsun-Kong; Sun, Xuhui; Lee, Shuit-Tong

2015-06-07

The hybrids of carbon nanotubes (CNTs) and the supported Ni nanoparticles (NPs) have been studied by scanning transmission X-ray microscopy (STXM) and tested by the hydrolysis reaction of ammonia borane (AB, NH3BH3). Data clearly showed the existence of a strong interaction between Ni NPs and thin CNTs (C-O-Ni bonds), which favored the tunable (buffer) electronic structure of Ni NPs facilitating the catalytic process. The hydrolysis process of AB confirmed the hypothesis that the hybrids with a strong interfacial interaction would show superior catalytic performance, while the hybrids with a weak interfacial interaction show poor performance. Our results provide a wealth of detailed information regarding the electronic structure of the NP-CNT hybrids and provide guidance towards the rational design of high-performance catalysts for energy applications.

Mechanism and Substrate Recognition of Human Holo ACP Synthase

PubMed Central

Bunkoczi, Gabor; Pasta, Saloni; Joshi, Anil; Wu, Xiaoqiu; Kavanagh, Kathryn L.; Smith, Stuart; Oppermann, Udo

2007-01-01

Summary Mammals utilize a single phosphopantetheinyl transferase for the posttranslational modification of at least three different apoproteins: the carrier protein components of cytosolic and mitochondrial fatty acid synthases and the aminoadipate semialdehyde reductase involved in lysine degradation. We determined the crystal structure of the human phosphopantetheinyl transferase, a eukaryotic phosphopantetheinyl transferase characterized, complexed with CoA and Mg2+, and in ternary complex with CoA and ACP. The involvement of key residues in ligand binding and catalysis was confirmed by mutagenesis and kinetic analysis. Human phosphopantetheinyl transferase exhibits an α/β fold and 2-fold pseudosymmetry similar to the Sfp phosphopantetheinyl transferase from Bacillus subtilis. Although the bound ACP exhibits a typical four-helix structure, its binding is unusual in that it is facilitated predominantly by hydrophobic interactions. A detailed mechanism is proposed describing the substrate binding and catalytic process. PMID:18022563

RNA-Seq-Based Transcript Structure Analysis with TrBorderExt.

PubMed

Wang, Yejun; Sun, Ming-An; White, Aaron P

2018-01-01

RNA-Seq has become a routine strategy for genome-wide gene expression comparisons in bacteria. Despite lower resolution in transcript border parsing compared with dRNA-Seq, TSS-EMOTE, Cappable-seq, Term-seq, and others, directional RNA-Seq still illustrates its advantages: low cost, quantification and transcript border analysis with a medium resolution (±10-20 nt). To facilitate mining of directional RNA-Seq datasets especially with respect to transcript structure analysis, we developed a tool, TrBorderExt, which can parse transcript start sites and termination sites accurately in bacteria. A detailed protocol is described in this chapter for how to use the software package step by step to identify bacterial transcript borders from raw RNA-Seq data. The package was developed with Perl and R programming languages, and is accessible freely through the website: http://www.szu-bioinf.org/TrBorderExt .

Food allergen protein families and their structural characteristics and application in component-resolved diagnosis: new data from the EuroPrevall project.

PubMed

Hoffmann-Sommergruber, Karin; Mills, E N Clare

2009-09-01

A large number of food allergens able to induce allergic symptoms in predisposed individuals, including severe, even life-threatening reactions, have been identified and characterized. However, proteins able to cause such IgE-mediated reactions can be assigned to only a limited number of protein families. Detailed knowledge about the characteristics of food allergens, their 3D structures, biological activity and stability, will help to improve diagnosis of food allergy, avoid unnecessary exclusion diets and assess the risk of cross-reactive allergies to other food sources. This review is dedicated to summarizing current knowledge about the most important food allergen protein families and to presenting data from the EuroPrevall allergen library, a proof-of-concept collection of highly purified, characterized and authenticated food allergens from animal and plant food sources to facilitate improved diagnosis of food allergies.

Some legal concerns with the use of crowd-sourced Geospatial Information

NASA Astrophysics Data System (ADS)

Cho, George

2014-06-01

Volunteered geographic Information (VGI), citizens as sensors, crowd-sourcing and 'Wikipedia' of maps have been used to describe activity facilitated by the Internet and the dynamic Web 2.0 environment to collect geographic information (GI). Legal concerns raised in the creation, assembly and dissemination of GI by produsers include: quality, ownership and liability. In detail, accuracy and authoritativeness of the crowd-sourced GI; the ownership and moral rights to the information, and contractual and tort liability are key concerns. A legal framework and governance structure may be necessary whereby technology, networked governance and provision of legal protections may be combined to mitigate geo-liability as a 'chilling' factor in VGI development.

Low-loss polarization-maintaining terahertz fiber based on central air hole movements

NASA Astrophysics Data System (ADS)

Wu, Zhiqing; Li, Qingzhi; Xia, Handing; Shi, Zhaohua; Zhou, Xiaoyan; Deng, Qinghua; Wu, Weidong

2018-04-01

We report a type of single-hole core photonic crystal fiber for low-loss polarization-maintaining terahertz (THz) wave guidance. Simulation results show that high birefringence at a level of 10 - 2 can be obtained by a design of minor position adjustment of the central air hole. Low effective material loss can be achieved because of the introduced central air hole. The strategy of the central air hole movements is also applicable for the three-hole core THz photonic crystal fibers. Other transmission characteristics including single-mode condition, power fraction, confinement loss, and dispersion were discussed in detail. It is quite clear that the proposal facilitates the fabrication process due to the simple structure.

Experimental Systems to Study Yeast Pexophagy.

PubMed

Yamashita, Shun-Ichi; Oku, Masahide; Sakai, Yasuyoshi; Fujiki, Yukio

2017-01-01

Peroxisome abundance is tightly regulated according to the physiological contexts, through regulations of both proliferation and degradation of the organelles. Here, we describe detailed methods to analyze processes for autophagic degradation of peroxisomes, termed pexophagy, in yeast organisms. The assay systems include a method for biochemical detection of pexophagy completion, and one for microscopic visualization of specialized membrane structures acting in pexophagy. As a model yeast organism utilized in studies of pexophagy, the methylotrophic yeast Komagataella phaffii (Pichia pastoris) is referred to in this chapter and related information on the studies with baker's yeast (Saccharomyces cerevisiae) is also included. The described techniques facilitate elucidation of molecular machineries for pexophagy and understanding of peroxisome-selective autophagic pathways.

A revisit to the requirements methodologies for services provided by the Office of Space Communications

NASA Technical Reports Server (NTRS)

Fishkind, Stanley; Harris, Richard N.; Pfeiffer, William A.

1996-01-01

The methodologies of the NASA requirements processing system, originally designed to enhance NASA's customer interface and response time, are reviewed. The response of NASA to the problems associated with the system is presented, and it is shown what was done to facilitate the process and to improve customer relations. The requirements generation system (RGS), a computer-supported client-server system, adopted by NASA is presented. The RGS system is configurable on a per-mission basis and can be structured to allow levels of requirements. The details provided concerning the RGS include the recommended configuration, information on becoming an RGS user and network connectivity worksheets for computer users.

An online database for informing ecological network models: http://kelpforest.ucsc.edu.

PubMed

Beas-Luna, Rodrigo; Novak, Mark; Carr, Mark H; Tinker, Martin T; Black, August; Caselle, Jennifer E; Hoban, Michael; Malone, Dan; Iles, Alison

2014-01-01

Ecological network models and analyses are recognized as valuable tools for understanding the dynamics and resiliency of ecosystems, and for informing ecosystem-based approaches to management. However, few databases exist that can provide the life history, demographic and species interaction information necessary to parameterize ecological network models. Faced with the difficulty of synthesizing the information required to construct models for kelp forest ecosystems along the West Coast of North America, we developed an online database (http://kelpforest.ucsc.edu/) to facilitate the collation and dissemination of such information. Many of the database's attributes are novel yet the structure is applicable and adaptable to other ecosystem modeling efforts. Information for each taxonomic unit includes stage-specific life history, demography, and body-size allometries. Species interactions include trophic, competitive, facilitative, and parasitic forms. Each data entry is temporally and spatially explicit. The online data entry interface allows researchers anywhere to contribute and access information. Quality control is facilitated by attributing each entry to unique contributor identities and source citations. The database has proven useful as an archive of species and ecosystem-specific information in the development of several ecological network models, for informing management actions, and for education purposes (e.g., undergraduate and graduate training). To facilitate adaptation of the database by other researches for other ecosystems, the code and technical details on how to customize this database and apply it to other ecosystems are freely available and located at the following link (https://github.com/kelpforest-cameo/databaseui).

An Online Database for Informing Ecological Network Models: http://kelpforest.ucsc.edu

PubMed Central

Beas-Luna, Rodrigo; Novak, Mark; Carr, Mark H.; Tinker, Martin T.; Black, August; Caselle, Jennifer E.; Hoban, Michael; Malone, Dan; Iles, Alison

2014-01-01

Ecological network models and analyses are recognized as valuable tools for understanding the dynamics and resiliency of ecosystems, and for informing ecosystem-based approaches to management. However, few databases exist that can provide the life history, demographic and species interaction information necessary to parameterize ecological network models. Faced with the difficulty of synthesizing the information required to construct models for kelp forest ecosystems along the West Coast of North America, we developed an online database (http://kelpforest.ucsc.edu/) to facilitate the collation and dissemination of such information. Many of the database's attributes are novel yet the structure is applicable and adaptable to other ecosystem modeling efforts. Information for each taxonomic unit includes stage-specific life history, demography, and body-size allometries. Species interactions include trophic, competitive, facilitative, and parasitic forms. Each data entry is temporally and spatially explicit. The online data entry interface allows researchers anywhere to contribute and access information. Quality control is facilitated by attributing each entry to unique contributor identities and source citations. The database has proven useful as an archive of species and ecosystem-specific information in the development of several ecological network models, for informing management actions, and for education purposes (e.g., undergraduate and graduate training). To facilitate adaptation of the database by other researches for other ecosystems, the code and technical details on how to customize this database and apply it to other ecosystems are freely available and located at the following link (https://github.com/kelpforest-cameo/databaseui). PMID:25343723

An online database for informing ecological network models: http://kelpforest.ucsc.edu

USGS Publications Warehouse

Beas-Luna, Rodrigo; Tinker, M. Tim; Novak, Mark; Carr, Mark H.; Black, August; Caselle, Jennifer E.; Hoban, Michael; Malone, Dan; Iles, Alison C.

2014-01-01

Ecological network models and analyses are recognized as valuable tools for understanding the dynamics and resiliency of ecosystems, and for informing ecosystem-based approaches to management. However, few databases exist that can provide the life history, demographic and species interaction information necessary to parameterize ecological network models. Faced with the difficulty of synthesizing the information required to construct models for kelp forest ecosystems along the West Coast of North America, we developed an online database (http://kelpforest.ucsc.edu/) to facilitate the collation and dissemination of such information. Many of the database's attributes are novel yet the structure is applicable and adaptable to other ecosystem modeling efforts. Information for each taxonomic unit includes stage-specific life history, demography, and body-size allometries. Species interactions include trophic, competitive, facilitative, and parasitic forms. Each data entry is temporally and spatially explicit. The online data entry interface allows researchers anywhere to contribute and access information. Quality control is facilitated by attributing each entry to unique contributor identities and source citations. The database has proven useful as an archive of species and ecosystem-specific information in the development of several ecological network models, for informing management actions, and for education purposes (e.g., undergraduate and graduate training). To facilitate adaptation of the database by other researches for other ecosystems, the code and technical details on how to customize this database and apply it to other ecosystems are freely available and located at the following link (https://github.com/kelpforest-cameo/data​baseui).

The value of continuing professional development: A realistic evaluation of a multi-disciplinary workshop for health visitors dealing with children with complex needs.

PubMed

Steven, Alison; Larkin, Valerie; Stewart, Jane; Bateman, Belinda

2018-08-01

Continuing Professional Development is important for maintaining and developing knowledge and skills. Evidence regarding direct impact on practice is limited. Existing literature often lacks sufficient detail regarding the initiative or its evaluation, making transferability problematic. To explore the impact and perceived value of multi-disciplinary Continuing Professional Development workshops for Health Visitors who support families with children with complex health needs. Realistic Evaluation principles guided the research. Workshop attendees were invited to participate (n.21), 81% (n.17) agreed. Data collection included a questionnaire and semi-structured interviews. Data analysis included descriptive statistics and qualitative thematic analysis. One North of England Health Service Trust. Interrelated temporal themes emerged. Before the workshop expectations included, uncertainty regarding content and ambiguity regarding attendance. During workshops comments focused on networking opportunities, the detail, content and facilitation of the learning experience. 'Emotional safety' enabled interaction, sharing and absorption of information, and potentially increased trust, confidence and social capital. Participants viewed the workshop as informative, enhancing insight regarding roles, services and processes. Post-workshop participants reported examples of practice enhancements attributed to workshop attendance including: confidence building; improved team working; facilitation of early referral and accessing additional support for families. Findings suggest initiative developers aiming CPD at new or existing teams need to consider nurturing social capital and to pay attention to the context and mechanisms, which can prompt attendance, engagement and subsequent practice application. Copyright © 2018 Elsevier Ltd. All rights reserved.

Accounting for ecosystem assets using remote sensing in the Colombian Orinoco River basin lowlands

NASA Astrophysics Data System (ADS)

Vargas, Leonardo; Hein, Lars; Remme, Roy P.

2016-10-01

In many parts of the world, ecosystems change compromises the supply of ecosystem services (ES). Better ecosystem management requires detailed and structured information. Ecosystem accounting has been developed as an information system for ecosystems, using concepts and valuation approaches that are aligned with the System of National Accounts (SNA). The SNA is used to store and analyse economic data, and the alignment of ecosystem accounts with the SNA facilitates the integrated analysis of economic and ecological aspects of ecosystem use. Ecosystem accounting requires detailed spatial information at aggregated scales. The objective of this paper is to explore how remote sensing images can be used to analyse ecosystems using an accounting approach in the Orinoco river basin. We assessed ecosystem assets in terms of extent, condition and capacity to supply ES. We focus on four specific ES: grasslands grazed by cattle, timber and oil palm harvest, and carbon sequestration. We link ES with six ecosystem assets; savannahs, woody grasslands, mixed agro-ecosystems, very dense forests, dense forest and oil palm plantations. We used remote sensing vegetation, surface temperature and productivity indexes to measure ecosystem assets. We found that remote sensing is a powerful tool to estimate ecosystem extent. The enhanced vegetation index can be used to assess ecosystems condition, and net primary productivity can be used for the assessment of ecosystem assets capacity to supply ES. Integrating remote sensing and ecological information facilitates efficient monitoring of ecosystem assets, in particular in data poor contexts.

Integrating prior information into microwave tomography Part 1: Impact of detail on image quality.

PubMed

Kurrant, Douglas; Baran, Anastasia; LoVetri, Joe; Fear, Elise

2017-12-01

The authors investigate the impact that incremental increases in the level of detail of patient-specific prior information have on image quality and the convergence behavior of an inversion algorithm in the context of near-field microwave breast imaging. A methodology is presented that uses image quality measures to characterize the ability of the algorithm to reconstruct both internal structures and lesions embedded in fibroglandular tissue. The approach permits key aspects that impact the quality of reconstruction of these structures to be identified and quantified. This provides insight into opportunities to improve image reconstruction performance. Patient-specific information is acquired using radar-based methods that form a regional map of the breast. This map is then incorporated into a microwave tomography algorithm. Previous investigations have demonstrated the effectiveness of this approach to improve image quality when applied to data generated with two-dimensional (2D) numerical models. The present study extends this work by generating prior information that is customized to vary the degree of structural detail to facilitate the investigation of the role of prior information in image formation. Numerical 2D breast models constructed from magnetic resonance (MR) scans, and reconstructions formed with a three-dimensional (3D) numerical breast model are used to assess if trends observed for the 2D results can be extended to 3D scenarios. For the blind reconstruction scenario (i.e., no prior information), the breast surface is not accurately identified and internal structures are not clearly resolved. A substantial improvement in image quality is achieved by incorporating the skin surface map and constraining the imaging domain to the breast. Internal features within the breast appear in the reconstructed image. However, it is challenging to discriminate between adipose and glandular regions and there are inaccuracies in both the structural properties of the glandular region and the dielectric properties reconstructed within this structure. Using a regional map with a skin layer only marginally improves this situation. Increasing the structural detail in the prior information to include internal features leads to reconstructions for which the interface that delineates the fat and gland regions can be inferred. Different features within the glandular region corresponding to tissues with varying relative permittivity values, such as a lesion embedded within glandular structure, emerge in the reconstructed images. Including knowledge of the breast surface and skin layer leads to a substantial improvement in image quality compared to the blind case, but the images have limited diagnostic utility for applications such as tumor response tracking. The diagnostic utility of the reconstruction technique is improved considerably when patient-specific structural information is used. This qualitative observation is supported quantitatively with image metrics. © 2017 American Association of Physicists in Medicine.

Chemical laser exhaust pipe design research

NASA Astrophysics Data System (ADS)

Sun, Yunqiang; Huang, Zhilong; Chen, Zhiqiang; Ren, Zebin; Guo, Longde

2016-10-01

In order to weaken the chemical laser exhaust gas influence of the optical transmission, a vent pipe is advised to emissions gas to the outside of the optical transmission area. Based on a variety of exhaust pipe design, a flow field characteristic of the pipe is carried out by numerical simulation and analysis in detail. The research results show that for uniform deflating exhaust pipe, although the pipeline structure is cyclical and convenient for engineering implementation, but there is a phenomenon of air reflows at the pipeline entrance slit which can be deduced from the numerical simulation results. So, this type of pipeline structure does not guarantee seal. For the design scheme of putting the pipeline contract part at the end of the exhaust pipe, or using the method of local area or tail contraction, numerical simulation results show that backflow phenomenon still exists at the pipeline entrance slit. Preliminary analysis indicates that the contraction of pipe would result in higher static pressure near the wall for the low speed flow field, so as to produce counter pressure gradient at the entrance slit. In order to eliminate backflow phenomenon at the pipe entrance slit, concerned with the pipeline type of radial size increase gradually along the flow, flow field property in the pipe is analyzed in detail by numerical simulation methods. Numerical simulation results indicate that there is not reflow phenomenon at entrance slit of the dilated duct. However the cold air inhaled in the slit which makes the temperature of the channel wall is lower than the center temperature. Therefore, this kind of pipeline structure can not only prevent the leak of the gas, but also reduce the wall temperature. In addition, compared with the straight pipe connection way, dilated pipe structure also has periodic structure, which can facilitate system integration installation.

Automatic recognition of conceptualization zones in scientific articles and two life science applications.

PubMed

Liakata, Maria; Saha, Shyamasree; Dobnik, Simon; Batchelor, Colin; Rebholz-Schuhmann, Dietrich

2012-04-01

Scholarly biomedical publications report on the findings of a research investigation. Scientists use a well-established discourse structure to relate their work to the state of the art, express their own motivation and hypotheses and report on their methods, results and conclusions. In previous work, we have proposed ways to explicitly annotate the structure of scientific investigations in scholarly publications. Here we present the means to facilitate automatic access to the scientific discourse of articles by automating the recognition of 11 categories at the sentence level, which we call Core Scientific Concepts (CoreSCs). These include: Hypothesis, Motivation, Goal, Object, Background, Method, Experiment, Model, Observation, Result and Conclusion. CoreSCs provide the structure and context to all statements and relations within an article and their automatic recognition can greatly facilitate biomedical information extraction by characterizing the different types of facts, hypotheses and evidence available in a scientific publication. We have trained and compared machine learning classifiers (support vector machines and conditional random fields) on a corpus of 265 full articles in biochemistry and chemistry to automatically recognize CoreSCs. We have evaluated our automatic classifications against a manually annotated gold standard, and have achieved promising accuracies with 'Experiment', 'Background' and 'Model' being the categories with the highest F1-scores (76%, 62% and 53%, respectively). We have analysed the task of CoreSC annotation both from a sentence classification as well as sequence labelling perspective and we present a detailed feature evaluation. The most discriminative features are local sentence features such as unigrams, bigrams and grammatical dependencies while features encoding the document structure, such as section headings, also play an important role for some of the categories. We discuss the usefulness of automatically generated CoreSCs in two biomedical applications as well as work in progress. A web-based tool for the automatic annotation of articles with CoreSCs and corresponding documentation is available online at http://www.sapientaproject.com/software http://www.sapientaproject.com also contains detailed information pertaining to CoreSC annotation and links to annotation guidelines as well as a corpus of manually annotated articles, which served as our training data. liakata@ebi.ac.uk Supplementary data are available at Bioinformatics online.

Population-based 3D genome structure analysis reveals driving forces in spatial genome organization

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

Tjong, Harianto; Li, Wenyuan; Kalhor, Reza

Conformation capture technologies (e.g., Hi-C) chart physical interactions between chromatin regions on a genome-wide scale. However, the structural variability of the genome between cells poses a great challenge to interpreting ensemble-averaged Hi-C data, particularly for long-range and interchromosomal interactions. Here, we present a probabilistic approach for deconvoluting Hi-C data into a model population of distinct diploid 3D genome structures, which facilitates the detection of chromatin interactions likely to co-occur in individual cells. Here, our approach incorporates the stochastic nature of chromosome conformations and allows a detailed analysis of alternative chromatin structure states. For example, we predict and experimentally confirm themore » presence of large centromere clusters with distinct chromosome compositions varying between individual cells. The stability of these clusters varies greatly with their chromosome identities. We show that these chromosome-specific clusters can play a key role in the overall chromosome positioning in the nucleus and stabilizing specific chromatin interactions. By explicitly considering genome structural variability, our population-based method provides an important tool for revealing novel insights into the key factors shaping the spatial genome organization.« less

Population-based 3D genome structure analysis reveals driving forces in spatial genome organization

DOE PAGES

Tjong, Harianto; Li, Wenyuan; Kalhor, Reza; ...

2016-03-07

Conformation capture technologies (e.g., Hi-C) chart physical interactions between chromatin regions on a genome-wide scale. However, the structural variability of the genome between cells poses a great challenge to interpreting ensemble-averaged Hi-C data, particularly for long-range and interchromosomal interactions. Here, we present a probabilistic approach for deconvoluting Hi-C data into a model population of distinct diploid 3D genome structures, which facilitates the detection of chromatin interactions likely to co-occur in individual cells. Here, our approach incorporates the stochastic nature of chromosome conformations and allows a detailed analysis of alternative chromatin structure states. For example, we predict and experimentally confirm themore » presence of large centromere clusters with distinct chromosome compositions varying between individual cells. The stability of these clusters varies greatly with their chromosome identities. We show that these chromosome-specific clusters can play a key role in the overall chromosome positioning in the nucleus and stabilizing specific chromatin interactions. By explicitly considering genome structural variability, our population-based method provides an important tool for revealing novel insights into the key factors shaping the spatial genome organization.« less

Functional Architecture of the Retina: Development and Disease

PubMed Central

Hoon, Mrinalini; Okawa, Haruhisa; Santina, Luca Della; Wong, Rachel O.L.

2014-01-01

Structure and function are highly correlated in the vertebrate retina, a sensory tissue that is organized into cell layers with microcircuits working in parallel and together to encode visual information. All vertebrate retinas share a fundamental plan, comprising five major neuronal cell classes with cell body distributions and connectivity arranged in stereotypic patterns. Conserved features in retinal design have enabled detailed analysis and comparisons of structure, connectivity and function across species. Each species, however, can adopt structural and/or functional retinal specializations, implementing variations to the basic design in order to satisfy unique requirements in visual function. Recent advances in molecular tools, imaging and electrophysiological approaches have greatly facilitated identification of the cellular and molecular mechanisms that establish the fundamental organization of the retina and the specializations of its microcircuits during development. Here, we review advances in our understanding of how these mechanisms act to shape structure and function at the single cell level, to coordinate the assembly of cell populations, and to define their specific circuitry. We also highlight how structure is rearranged and function is disrupted in disease, and discuss current approaches to re-establish the intricate functional architecture of the retina. PMID:24984227

Functional architecture of the retina: development and disease.

PubMed

Hoon, Mrinalini; Okawa, Haruhisa; Della Santina, Luca; Wong, Rachel O L

2014-09-01

Structure and function are highly correlated in the vertebrate retina, a sensory tissue that is organized into cell layers with microcircuits working in parallel and together to encode visual information. All vertebrate retinas share a fundamental plan, comprising five major neuronal cell classes with cell body distributions and connectivity arranged in stereotypic patterns. Conserved features in retinal design have enabled detailed analysis and comparisons of structure, connectivity and function across species. Each species, however, can adopt structural and/or functional retinal specializations, implementing variations to the basic design in order to satisfy unique requirements in visual function. Recent advances in molecular tools, imaging and electrophysiological approaches have greatly facilitated identification of the cellular and molecular mechanisms that establish the fundamental organization of the retina and the specializations of its microcircuits during development. Here, we review advances in our understanding of how these mechanisms act to shape structure and function at the single cell level, to coordinate the assembly of cell populations, and to define their specific circuitry. We also highlight how structure is rearranged and function is disrupted in disease, and discuss current approaches to re-establish the intricate functional architecture of the retina. Copyright © 2014 Elsevier Ltd. All rights reserved.

Enhancement of a Virtual Geology Field Guide of Georgia Initiative Using Gigapan© and ArcGIS Online's Story Map

NASA Astrophysics Data System (ADS)

Mobasher, K.; Turk, H. J.; Witherspoon, W.; Tate, L.; Hoynes, J.

2015-12-01

A GIS geology geodatabase of Georgia was developed using ArcGIS 10.2. The geodatabase for each physiographic provinces of Georgia contains fields designed to store information regarding geologic features. Using ArcGIS online, the virtual field guide is created which provides an interactive learning experience for students to allow in real time photography, description, mapping and sharing their observations with the instructor and peers. Gigapan© facilitates visualizing geologic features at different scales with high resolutions and in their larger surrounding context. The classroom applications of the Gigapan© are limitless when teaching students the entire range of geologic structures from showcasing crystalline structures of minerals to understanding the geological processes responsible for formation of an entire mountain range. The addition of the Story Map enhances the virtual experience when you want to present a geo-located story point narrative featuring images or videos. The virtual field component and supplementary Gigapan© imagery coupled with Story Map added significantly to the detailed realism of virtual field guide further allowing students to more fully understand geological concepts at various scales. These technologies peaked students interest and facilitated their learning and preparation to function more effectively in the geosciences by developing better observations and new skills. These technologies facilitated increased student engagement in the geosciences by sharing, enhancing and transferring lecture information to actual field knowledge and experiences. This enhanced interactive learning experience not only begins to allow students to understand and recognize geologic features in the field but also increased their collaboration, enthusiasm and interest in the discipline. The increased interest and collaboration occurred as students assisted in populating a geologic geodatabase of Georgia.

Multiscale multimodal fusion of histological and MRI volumes for characterization of lung inflammation

NASA Astrophysics Data System (ADS)

Rusu, Mirabela; Wang, Haibo; Golden, Thea; Gow, Andrew; Madabhushi, Anant

2013-03-01

Mouse lung models facilitate the investigation of conditions such as chronic inflammation which are associated with common lung diseases. The multi-scale manifestation of lung inflammation prompted us to use multi-scale imaging - both in vivo, ex vivo MRI along with ex vivo histology, for its study in a new quantitative way. Some imaging modalities, such as MRI, are non-invasive and capture macroscopic features of the pathology, while others, e.g. ex vivo histology, depict detailed structures. Registering such multi-modal data to the same spatial coordinates will allow the construction of a comprehensive 3D model to enable the multi-scale study of diseases. Moreover, it may facilitate the identification and definition of quantitative of in vivo imaging signatures for diseases and pathologic processes. We introduce a quantitative, image analytic framework to integrate in vivo MR images of the entire mouse with ex vivo histology of the lung alone, using lung ex vivo MRI as conduit to facilitate their co-registration. In our framework, we first align the MR images by registering the in vivo and ex vivo MRI of the lung using an interactive rigid registration approach. Then we reconstruct the 3D volume of the ex vivo histological specimen by efficient group wise registration of the 2D slices. The resulting 3D histologic volume is subsequently registered to the MRI volumes by interactive rigid registration, directly to the ex vivo MRI, and implicitly to in vivo MRI. Qualitative evaluation of the registration framework was performed by comparing airway tree structures in ex vivo MRI and ex vivo histology where airways are visible and may be annotated. We present a use case for evaluation of our co-registration framework in the context of studying chronic inammation in a diseased mouse.

A Global Comparison of the Human and T. brucei Degradomes Gives Insights about Possible Parasite Drug Targets

PubMed Central

Mashiyama, Susan T.; Koupparis, Kyriacos; Caffrey, Conor R.; McKerrow, James H.; Babbitt, Patricia C.

2012-01-01

We performed a genome-level computational study of sequence and structure similarity, the latter using crystal structures and models, of the proteases of Homo sapiens and the human parasite Trypanosoma brucei. Using sequence and structure similarity networks to summarize the results, we constructed global views that show visually the relative abundance and variety of proteases in the degradome landscapes of these two species, and provide insights into evolutionary relationships between proteases. The results also indicate how broadly these sequence sets are covered by three-dimensional structures. These views facilitate cross-species comparisons and offer clues for drug design from knowledge about the sequences and structures of potential drug targets and their homologs. Two protease groups (“M32” and “C51”) that are very different in sequence from human proteases are examined in structural detail, illustrating the application of this global approach in mining new pathogen genomes for potential drug targets. Based on our analyses, a human ACE2 inhibitor was selected for experimental testing on one of these parasite proteases, TbM32, and was shown to inhibit it. These sequence and structure data, along with interactive versions of the protein similarity networks generated in this study, are available at http://babbittlab.ucsf.edu/resources.html. PMID:23236535

Hydrothermal synthesis of novel Mn3O4 nano-octahedrons with enhanced supercapacitors performances

NASA Astrophysics Data System (ADS)

Jiang, Hao; Zhao, Ting; Yan, Chaoyi; Ma, Jan; Li, Chunzhong

2010-10-01

Uniform and single-crystalline Mn3O4 nano-octahedrons have been successfully synthesized by a simple ethylenediaminetetraacetic acid disodium salt (EDTA-2Na) assisted hydrothermal route. The octahedron structures exhibit a high geometric symmetry with smooth surfaces and the mean side length of square base of octahedrons is ~160 nm. The structure is reckoned to provide superior functional properties and the nano-size achieved in the present work is noted to further facilitate the material property enhancement. The formation process was proposed to begin with a ``dissolution-recrystallization'' which is followed by an ``Ostwald ripening'' mechanism. The Mn3O4 nano-octahedrons exhibited an enhanced specific capacitance of 322 F g-1 compared with the truncated octahedrons with specific capacitances of 244 F g-1, making them a promising electrode material for supercapacitors.Uniform and single-crystalline Mn3O4 nano-octahedrons have been successfully synthesized by a simple ethylenediaminetetraacetic acid disodium salt (EDTA-2Na) assisted hydrothermal route. The octahedron structures exhibit a high geometric symmetry with smooth surfaces and the mean side length of square base of octahedrons is ~160 nm. The structure is reckoned to provide superior functional properties and the nano-size achieved in the present work is noted to further facilitate the material property enhancement. The formation process was proposed to begin with a ``dissolution-recrystallization'' which is followed by an ``Ostwald ripening'' mechanism. The Mn3O4 nano-octahedrons exhibited an enhanced specific capacitance of 322 F g-1 compared with the truncated octahedrons with specific capacitances of 244 F g-1, making them a promising electrode material for supercapacitors. Electronic supplementary information (ESI) available: TEM images; EDTA-2Na reaction details. See DOI: 10.1039/c0nr00257g

Sling, Scoop, and Squirter: Anatomical Features Facilitating Prey Transport, Processing, and Swallowing in Rorqual Whales (Mammalia: Balaenopteridae).

PubMed

Werth, Alexander J; Ito, Haruka

2017-11-01

Much is known about lunge feeding in balaenopterid whales, but many key aspects of structure, function, and behavior have not yet been explained in detail, especially with regard to concentrating, positioning, and swallowing large aggregations of prey. We describe a novel system of three integrated structural components, all of which are involved in sequential feeding activities (intraoral transport, filtration, and swallowing of prey) that follow lunge-feeding engulfment of prey-laden water in rorquals: (1) a hammock-like muscular sling comprising extrinsic lingual musculature along the midline of the ventral pouch; (2) the flattened scoop-like arrangement of caudal-most baleen plates converging in the oropharynx adjacent to the esophageal opening; and (3) a flow-diverting flange at the posterior dorsum of the lip, by a flow channel at the angle of the mouth. Subsequent to contraction of the ventral pouch and concomitant expulsion of the mouthful of ingested water, these three structures together, we contend, aid in (1) channeling prey posteriorly toward the esophageal opening; (2) concentrating prey as excess water is squeezed from (what is presumed to be) the slurry-like mixture of nektonic and/or planktonic prey and water; and (3) guiding prey into the isthmus of the fauces while simultaneously (4) facilitating expulsion of water. These related functions occur along with, and are in part achieved by, elevation and retraction of the tongue and oral floor. Given their presumed functional role, these systems are best described as a suite of integrated structural adaptations. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 300:2070-2086, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Dimension and bridging ligand effects on Mo-mediated catalytic transformation of dinitrogen to ammonia: Chain-like extended models of Nishibayashi’s catalyst

DOE PAGES

Sheng, Xiao -Lan; Batista, Enrique Ricardo; Duan, Yi -Xiang; ...

2016-11-01

Previous studies suggested that in Nishibayashi’s homogenous catalytic systems based on molybdenum (Mo) complexes, the bimetallic structure facilitated dinitrogen to ammonia conversion in comparison to the corresponding monometallic complexes, likely due to the through-bond interactions between the two Mo centers. However, more detailed model systems are necessary to support this bimetallic hypothesis, and to elucidate the multi-metallic effects on the catalytic mechanism. In this work, we computationally examined the effects of dimension as well as the types of bridging ligands on the catalytic activities of molybdenum-dinitrogen complexes by using a set of extended model systems based on Nishibayashi’s bimetallic structure.more » The polynuclear chains containing four ([Mo] 4) or more Mo centers were found to drastically enhance the catalytic performance by comparing with both the monometallic and bimetallic complexes. Carbide ([:C≡C:] 2–) was found to be a more effective bridging ligand than N 2 in terms of electronic charges dispersion between metal centers thereby facilitating reactions in the catalytic cycle. Furthermore, the mechanistic modelling suggests that in principle, more efficient catalytic system for N 2 to NH 3 transformation might be obtained by extending the polynuclear chain to a proper size in combination with an effective bridging ligand for charge dispersion.« less

Dimension and bridging ligand effects on Mo-mediated catalytic transformation of dinitrogen to ammonia: Chain-like extended models of Nishibayashi’s catalyst

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

Sheng, Xiao -Lan; Batista, Enrique Ricardo; Duan, Yi -Xiang

Previous studies suggested that in Nishibayashi’s homogenous catalytic systems based on molybdenum (Mo) complexes, the bimetallic structure facilitated dinitrogen to ammonia conversion in comparison to the corresponding monometallic complexes, likely due to the through-bond interactions between the two Mo centers. However, more detailed model systems are necessary to support this bimetallic hypothesis, and to elucidate the multi-metallic effects on the catalytic mechanism. In this work, we computationally examined the effects of dimension as well as the types of bridging ligands on the catalytic activities of molybdenum-dinitrogen complexes by using a set of extended model systems based on Nishibayashi’s bimetallic structure.more » The polynuclear chains containing four ([Mo] 4) or more Mo centers were found to drastically enhance the catalytic performance by comparing with both the monometallic and bimetallic complexes. Carbide ([:C≡C:] 2–) was found to be a more effective bridging ligand than N 2 in terms of electronic charges dispersion between metal centers thereby facilitating reactions in the catalytic cycle. Furthermore, the mechanistic modelling suggests that in principle, more efficient catalytic system for N 2 to NH 3 transformation might be obtained by extending the polynuclear chain to a proper size in combination with an effective bridging ligand for charge dispersion.« less

Metal-coupled folding as the driving force for the extreme stability of Rad50 zinc hook dimer assembly

NASA Astrophysics Data System (ADS)

Kochańczyk, Tomasz; Nowakowski, Michał; Wojewska, Dominika; Kocyła, Anna; Ejchart, Andrzej; Koźmiński, Wiktor; Krężel, Artur

2016-11-01

The binding of metal ions at the interface of protein complexes presents a unique and poorly understood mechanism of molecular assembly. A remarkable example is the Rad50 zinc hook domain, which is highly conserved and facilitates the Zn2+-mediated homodimerization of Rad50 proteins. Here, we present a detailed analysis of the structural and thermodynamic effects governing the formation and stability (logK12 = 20.74) of this evolutionarily conserved protein assembly. We have dissected the determinants of the stability contributed by the small β-hairpin of the domain surrounding the zinc binding motif and the coiled-coiled regions using peptides of various lengths from 4 to 45 amino acid residues, alanine substitutions and peptide bond-to-ester perturbations. In the studied series of peptides, an >650 000-fold increase of the formation constant of the dimeric complex arises from favorable enthalpy because of the increased acidity of the cysteine thiols in metal-free form and the structural properties of the dimer. The dependence of the enthalpy on the domain fragment length is partially compensated by the entropic penalty of domain folding, indicating enthalpy-entropy compensation. This study facilitates understanding of the metal-mediated protein-protein interactions in which the metal ion is critical for the tight association of protein subunits.

Metal-coupled folding as the driving force for the extreme stability of Rad50 zinc hook dimer assembly

PubMed Central

Kochańczyk, Tomasz; Nowakowski, Michał; Wojewska, Dominika; Kocyła, Anna; Ejchart, Andrzej; Koźmiński, Wiktor; Krężel, Artur

2016-01-01

The binding of metal ions at the interface of protein complexes presents a unique and poorly understood mechanism of molecular assembly. A remarkable example is the Rad50 zinc hook domain, which is highly conserved and facilitates the Zn2+-mediated homodimerization of Rad50 proteins. Here, we present a detailed analysis of the structural and thermodynamic effects governing the formation and stability (logK12 = 20.74) of this evolutionarily conserved protein assembly. We have dissected the determinants of the stability contributed by the small β-hairpin of the domain surrounding the zinc binding motif and the coiled-coiled regions using peptides of various lengths from 4 to 45 amino acid residues, alanine substitutions and peptide bond-to-ester perturbations. In the studied series of peptides, an >650 000-fold increase of the formation constant of the dimeric complex arises from favorable enthalpy because of the increased acidity of the cysteine thiols in metal-free form and the structural properties of the dimer. The dependence of the enthalpy on the domain fragment length is partially compensated by the entropic penalty of domain folding, indicating enthalpy-entropy compensation. This study facilitates understanding of the metal-mediated protein-protein interactions in which the metal ion is critical for the tight association of protein subunits. PMID:27808280

Integrative Research and Intervention To Facilitate Child and Family Development, Education, Readiness for Head Start, and Family Self-Sufficiency.

ERIC Educational Resources Information Center

Lapidus, Leah Blumberg

This paper describes a project designed to facilitate and evaluate child and family mental health in the community, inside and outside of Head Start programs. Also detailed is a study of the effects of "Community Impact" programs and 6-week, focused, group interventions for children and families in programs predicted to increase…

Structures of Adenovirus Incomplete Particles Clarify Capsid Architecture and Show Maturation Changes of Packaging Protein L1 52/55k

PubMed Central

Condezo, Gabriela N.; Marabini, Roberto; Ayora, Silvia; Carazo, José M.; Alba, Raúl; Chillón, Miguel

2015-01-01

ABSTRACT Adenovirus is one of the most complex icosahedral, nonenveloped viruses. Even after its structure was solved at near-atomic resolution by both cryo-electron microscopy and X-ray crystallography, the location of minor coat proteins is still a subject of debate. The elaborated capsid architecture is the product of a correspondingly complex assembly process, about which many aspects remain unknown. Genome encapsidation involves the concerted action of five virus proteins, and proteolytic processing by the virus protease is needed to prime the virion for sequential uncoating. Protein L1 52/55k is required for packaging, and multiple cleavages by the maturation protease facilitate its release from the nascent virion. Light-density particles are routinely produced in adenovirus infections and are thought to represent assembly intermediates. Here, we present the molecular and structural characterization of two different types of human adenovirus light particles produced by a mutant with delayed packaging. We show that these particles lack core polypeptide V but do not lack the density corresponding to this protein in the X-ray structure, thereby adding support to the adenovirus cryo-electron microscopy model. The two types of light particles present different degrees of proteolytic processing. Their structures provide the first glimpse of the organization of L1 52/55k protein inside the capsid shell and of how this organization changes upon partial maturation. Immature, full-length L1 52/55k is poised beneath the vertices to engage the virus genome. Upon proteolytic processing, L1 52/55k disengages from the capsid shell, facilitating genome release during uncoating. IMPORTANCE Adenoviruses have been extensively characterized as experimental systems in molecular biology, as human pathogens, and as therapeutic vectors. However, a clear picture of many aspects of their basic biology is still lacking. Two of these aspects are the location of minor coat proteins in the capsid and the molecular details of capsid assembly. Here, we provide evidence supporting one of the two current models for capsid architecture. We also show for the first time the location of the packaging protein L1 52/55k in particles lacking the virus genome and how this location changes during maturation. Our results contribute to clarifying standing questions in adenovirus capsid architecture and provide new details on the role of L1 52/55k protein in assembly. PMID:26178997

iSAW: Integrating Structure, Actors, and Water to study socio-hydro-ecological systems

NASA Astrophysics Data System (ADS)

Hale, Rebecca L.; Armstrong, Andrea; Baker, Michelle A.; Bedingfield, Sean; Betts, David; Buahin, Caleb; Buchert, Martin; Crowl, Todd; Dupont, R. Ryan; Ehleringer, James R.; Endter-Wada, Joanna; Flint, Courtney; Grant, Jacqualine; Hinners, Sarah; Horsburgh, Jeffery S.; Jackson-Smith, Douglas; Jones, Amber S.; Licon, Carlos; Null, Sarah E.; Odame, Augustina; Pataki, Diane E.; Rosenberg, David; Runburg, Madlyn; Stoker, Philip; Strong, Courtenay

2015-03-01

Urbanization, climate, and ecosystem change represent major challenges for managing water resources. Although water systems are complex, a need exists for a generalized representation of these systems to identify important components and linkages to guide scientific inquiry and aid water management. We developed an integrated Structure-Actor-Water framework (iSAW) to facilitate the understanding of and transitions to sustainable water systems. Our goal was to produce an interdisciplinary framework for water resources research that could address management challenges across scales (e.g., plot to region) and domains (e.g., water supply and quality, transitioning, and urban landscapes). The framework was designed to be generalizable across all human-environment systems, yet with sufficient detail and flexibility to be customized to specific cases. iSAW includes three major components: structure (natural, built, and social), actors (individual and organizational), and water (quality and quantity). Key linkages among these components include: (1) ecological/hydrologic processes, (2) ecosystem/geomorphic feedbacks, (3) planning, design, and policy, (4) perceptions, information, and experience, (5) resource access and risk, and (6) operational water use and management. We illustrate the flexibility and utility of the iSAW framework by applying it to two research and management problems: understanding urban water supply and demand in a changing climate and expanding use of green storm water infrastructure in a semi-arid environment. The applications demonstrate that a generalized conceptual model can identify important components and linkages in complex and diverse water systems and facilitate communication about those systems among researchers from diverse disciplines.

Real-space identification of intermolecular bonding with atomic force microscopy.

PubMed

Zhang, Jun; Chen, Pengcheng; Yuan, Bingkai; Ji, Wei; Cheng, Zhihai; Qiu, Xiaohui

2013-11-01

We report a real-space visualization of the formation of hydrogen bonding in 8-hydroxyquinoline (8-hq) molecular assemblies on a Cu(111) substrate, using noncontact atomic force microscopy (NC-AFM). The atomically resolved molecular structures enable a precise determination of the characteristics of hydrogen bonding networks, including the bonding sites, orientations, and lengths. The observation of bond contrast was interpreted by ab initio density functional calculations, which indicated the electron density contribution from the hybridized electronic state of the hydrogen bond. Intermolecular coordination between the dehydrogenated 8-hq and Cu adatoms was also revealed by the submolecular resolution AFM characterization. The direct identification of local bonding configurations by NC-AFM would facilitate detailed investigations of intermolecular interactions in complex molecules with multiple active sites.

Reliable aluminum contact formation by electrostatic bonding

NASA Astrophysics Data System (ADS)

Kárpáti, T.; Pap, A. E.; Radnóczi, Gy; Beke, B.; Bársony, I.; Fürjes, P.

2015-07-01

The paper presents a detailed study of a reliable method developed for aluminum fusion wafer bonding assisted by the electrostatic force evolving during the anodic bonding process. The IC-compatible procedure described allows the parallel formation of electrical and mechanical contacts, facilitating a reliable packaging of electromechanical systems with backside electrical contacts. This fusion bonding method supports the fabrication of complex microelectromechanical systems (MEMS) and micro-opto-electromechanical systems (MOEMS) structures with enhanced temperature stability, which is crucial in mechanical sensor applications such as pressure or force sensors. Due to the applied electrical potential of  -1000 V the Al metal layers are compressed by electrostatic force, and at the bonding temperature of 450 °C intermetallic diffusion causes aluminum ions to migrate between metal layers.

Critical parameters of hard-core Yukawa fluids within the structural theory

NASA Astrophysics Data System (ADS)

Bahaa Khedr, M.; Osman, S. M.

2012-10-01

A purely statistical mechanical approach is proposed to account for the liquid-vapor critical point based on the mean density approximation (MDA) of the direct correlation function. The application to hard-core Yukawa (HCY) fluids facilitates the use of the series mean spherical approximation (SMSA). The location of the critical parameters for HCY fluid with variable intermolecular range is accurately calculated. Good agreement is observed with computer simulation results and with the inverse temperature expansion (ITE) predictions. The influence of the potential range on the critical parameters is demonstrated and the universality of the critical compressibility ratio is discussed. The behavior of the isochoric and isobaric heat capacities along the equilibrium line and the near vicinity of the critical point is discussed in details.

GIS based solid waste management information system for Nagpur, India.

PubMed

Vijay, Ritesh; Jain, Preeti; Sharma, N; Bhattacharyya, J K; Vaidya, A N; Sohony, R A

2013-01-01

Solid waste management is one of the major problems of today's world and needs to be addressed by proper utilization of technologies and design of effective, flexible and structured information system. Therefore, the objective of this paper was to design and develop a GIS based solid waste management information system as a decision making and planning tool for regularities and municipal authorities. The system integrates geo-spatial features of the city and database of existing solid waste management. GIS based information system facilitates modules of visualization, query interface, statistical analysis, report generation and database modification. It also provides modules like solid waste estimation, collection, transportation and disposal details. The information system is user-friendly, standalone and platform independent.

NV PFA Regional Data

DOE Data Explorer

James Faulds

2015-10-28

This project focused on defining geothermal play fairways and development of a detailed geothermal potential map of a large transect across the Great Basin region (96,000 km2), with the primary objective of facilitating discovery of commercial-grade, blind geothermal fields (i.e. systems with no surface hot springs or fumaroles) and thereby accelerating geothermal development in this promising region. Data included in this submission consists of: structural settings (target areas, recency of faulting, slip and dilation potential, slip rates, quality), regional-scale strain rates, earthquake density and magnitude, gravity data, temperature at 3 km depth, permeability models, favorability models, degree of exploration and exploration opportunities, data from springs and wells, transmission lines and wilderness areas, and published maps and theses for the Nevada Play Fairway area.

Development of use of an Operational Procedure Information System (OPIS) for future space missions

NASA Technical Reports Server (NTRS)

Illmer, N.; Mies, L.; Schoen, A.; Jain, A.

1994-01-01

A MS-Windows based electronic procedure system, called OPIS (Operational Procedure Information System), was developed. The system consists of two parts, the editor, for 'writing' the procedure and the notepad application, for the usage of the procedures by the crew during training and flight. The system is based on standardized, structured procedure format and language. It allows the embedding of sketches, photos, animated graphics and video sequences and the access to off-nominal procedures by linkage to an appropriate database. The system facilitates the work with procedures of different degrees of detail, depending on the training status of the crew. The development of a 'language module' for the automatic translation of the procedures, for example into Russian, is planned.

Do health care institutions value research? A mixed methods study of barriers and facilitators to methodological rigor in pediatric randomized trials.

PubMed

Hamm, Michele P; Scott, Shannon D; Klassen, Terry P; Moher, David; Hartling, Lisa

2012-10-18

Pediatric randomized controlled trials (RCTs) are susceptible to a high risk of bias. We examined the barriers and facilitators that pediatric trialists face in the design and conduct of unbiased trials. We used a mixed methods design, with semi-structured interviews building upon the results of a quantitative survey. We surveyed Canadian (n=253) and international (n=600) pediatric trialists regarding their knowledge and awareness of bias and their perceived barriers and facilitators in conducting clinical trials. We then interviewed 13 participants from different subspecialties and geographic locations to gain a more detailed description of how their experiences and attitudes towards research interacted with trial design and conduct. The survey response rate was 23.0% (186/807). 68.1% of respondents agreed that bias is a problem in pediatric RCTs and 72.0% felt that there is sufficient evidence to support changing some aspects of how trials are conducted. Knowledge related to bias was variable, with inconsistent awareness of study design features that may introduce bias into a study. Interview participants highlighted a lack of formal training in research methods, a negative research culture, and the pragmatics of trial conduct as barriers. Facilitators included contact with knowledgeable and supportive colleagues and infrastructure for research. A lack of awareness of bias and negative attitudes towards research present significant barriers in terms of conducting methodologically rigorous pediatric RCTs. Knowledge translation efforts must focus on these issues to ensure the relevance and validity of trial results.

Advanced electron microscopy characterization of tri-layer rare-earth oxide superlattices

NASA Astrophysics Data System (ADS)

Phillips, Patrick; Disa, Ankit; Ismail-Beigi, Sohrab; Klie, Robert; University of Illinois-Chicago Team; Yale University Team

2015-03-01

Rare-earth nickelates are known to display complex electronic and magnetic behaviors owed to a very localized and sensitive Ni-site atomic and electronic structure. Toward realizing the goal of manipulating of the energetic ordering of Ni d orbitals and 2D conduction, the present work focuses on the experimental characterization of thin film superlattice structures consisting of alternating layers of LaTiO3 and LaNiO3 sandwiched between a dull insulator, LaAlO3. Using advanced scanning transmission electron microscopy (STEM)-based methods, properties such as interfacial sharpness, electron transfer, O presence, and local electronic structure can be probed at the atomic scale, and will be discussed at length. By combining both energy dispersive X-ray (EDX) and electronic energy loss (EEL) spectroscopies in an aberration-corrected STEM, it is possible to attain energy and spatial resolutions of 0.35 eV and 100 pm, respectively. Focus of the talk will remain not only on the aforementioned properties, but will also include details and parameters of the acquisitions to facilitate future characterization at this level.

The anisotropic tunneling behavior of spin transport in graphene-based magnetic tunneling junction

NASA Astrophysics Data System (ADS)

Pan, Mengchun; Li, Peisen; Qiu, Weicheng; Zhao, Jianqiang; Peng, Junping; Hu, Jiafei; Hu, Jinghua; Tian, Wugang; Hu, Yueguo; Chen, Dixiang; Wu, Xuezhong; Xu, Zhongjie; Yuan, Xuefeng

2018-05-01

Due to the theoretical prediction of large tunneling magnetoresistance (TMR), graphene-based magnetic tunneling junction (MTJ) has become an important branch of high-performance spintronics device. In this paper, the non-collinear spin filtering and transport properties of MTJ with the Ni/tri-layer graphene/Ni structure were studied in detail by utilizing the non-equilibrium Green's formalism combined with spin polarized density functional theory. The band structure of Ni-C bonding interface shows that Ni-C atomic hybridization facilitates the electronic structure consistency of graphene and nickel, which results in a perfect spin filtering effect for tri-layer graphene-based MTJ. Furthermore, our theoretical results show that the value of tunneling resistance changes with the relative magnetization angle of two ferromagnetic layers, displaying the anisotropic tunneling behavior of graphene-based MTJ. This originates from the resonant conduction states which are strongly adjusted by the relative magnetization angles. In addition, the perfect spin filtering effect is demonstrated by fitting the anisotropic conductance with the Julliere's model. Our work may serve as guidance for researches and applications of graphene-based spintronics device.

Domain motions of Argonaute, the catalytic engine of RNA interference

PubMed Central

Ming, Dengming; Wall, Michael E; Sanbonmatsu, Kevin Y

2007-01-01

Background The Argonaute protein is the core component of the RNA-induced silencing complex, playing the central role of cleaving the mRNA target. Visual inspection of static crystal structures already has enabled researchers to suggest conformational changes of Argonaute that might occur during RNA interference. We have taken the next step by performing an all-atom normal mode analysis of the Pyrococcus furiosus and Aquifex aeolicus Argonaute crystal structures, allowing us to quantitatively assess the feasibility of these conformational changes. To perform the analysis, we begin with the energy-minimized X-ray structures. Normal modes are then calculated using an all-atom molecular mechanics force field. Results The analysis reveals low-frequency vibrations that facilitate the accommodation of RNA duplexes – an essential step in target recognition. The Pyrococcus furiosus and Aquifex aeolicus Argonaute proteins both exhibit low-frequency torsion and hinge motions; however, differences in the overall architecture of the proteins cause the detailed dynamics to be significantly different. Conclusion Overall, low-frequency vibrations of Argonaute are consistent with mechanisms within the current reaction cycle model for RNA interference. PMID:18053142

Structural, mutagenic and in silico studies of xyloglucan fucosylation in Arabidopsis thaliana suggest a water-mediated mechanism

DOE PAGES

Urbanowicz, Breeanna R.; Bharadwaj, Vivek S.; Alahuhta, Markus; ...

2017-07-03

The mechanistic underpinnings of the complex process of plant polysaccharide biosynthesis are poorly understood, largely due to the resistance of glycosyltransferase (GT) enzymes to structural characterization. In Arabidopsis thaliana, a glycosyl transferase family 37 (GT37) fucosyltransferase-1 (AtFUT1) catalyzes the regiospecific transfer of terminal 1,2-fucosyl residues to xyloglucan side chains - a key step in the biosynthesis of fucosylated sidechains of galactoxyloglucan. We unravel the mechanistic basis for fucosylation by AtFUT1 with a multipronged approach involving protein expression, X-ray crystallography, mutagenesis experiments and molecular simulations. Mammalian cell culture expressions enable sufficient production of the enzyme for X-ray crystallography, which reveals themore » structural architecture of AtFUT1 in complex with bound donor and acceptor substrate analogs. Here, the lack of an appropriately positioned active site residue as a catalytic base leads us to propose an atypical water-mediated fucosylation mechanism facilitated by an H-bonded network, which is corroborated by mutagenesis experiments as well as detailed atomistic simulations.« less

Domain motions of Argonaute, the catalytic engine of RNA interference.

PubMed

Ming, Dengming; Wall, Michael E; Sanbonmatsu, Kevin Y

2007-11-30

The Argonaute protein is the core component of the RNA-induced silencing complex, playing the central role of cleaving the mRNA target. Visual inspection of static crystal structures already has enabled researchers to suggest conformational changes of Argonaute that might occur during RNA interference. We have taken the next step by performing an all-atom normal mode analysis of the Pyrococcus furiosus and Aquifex aeolicus Argonaute crystal structures, allowing us to quantitatively assess the feasibility of these conformational changes. To perform the analysis, we begin with the energy-minimized X-ray structures. Normal modes are then calculated using an all-atom molecular mechanics force field. The analysis reveals low-frequency vibrations that facilitate the accommodation of RNA duplexes - an essential step in target recognition. The Pyrococcus furiosus and Aquifex aeolicus Argonaute proteins both exhibit low-frequency torsion and hinge motions; however, differences in the overall architecture of the proteins cause the detailed dynamics to be significantly different. Overall, low-frequency vibrations of Argonaute are consistent with mechanisms within the current reaction cycle model for RNA interference.

Anatomical guidance for functional near-infrared spectroscopy: AtlasViewer tutorial

PubMed Central

Aasted, Christopher M.; Yücel, Meryem A.; Cooper, Robert J.; Dubb, Jay; Tsuzuki, Daisuke; Becerra, Lino; Petkov, Mike P.; Borsook, David; Dan, Ippeita; Boas, David A.

2015-01-01

Abstract. Functional near-infrared spectroscopy (fNIRS) is an optical imaging method that is used to noninvasively measure cerebral hemoglobin concentration changes induced by brain activation. Using structural guidance in fNIRS research enhances interpretation of results and facilitates making comparisons between studies. AtlasViewer is an open-source software package we have developed that incorporates multiple spatial registration tools to enable structural guidance in the interpretation of fNIRS studies. We introduce the reader to the layout of the AtlasViewer graphical user interface, the folder structure, and user files required in the creation of fNIRS probes containing sources and detectors registered to desired locations on the head, evaluating probe fabrication error and intersubject probe placement variability, and different procedures for estimating measurement sensitivity to different brain regions as well as image reconstruction performance. Further, we detail how AtlasViewer provides a generic head atlas for guiding interpretation of fNIRS results, but also permits users to provide subject-specific head anatomies to interpret their results. We anticipate that AtlasViewer will be a valuable tool in improving the anatomical interpretation of fNIRS studies. PMID:26157991

IRaPPA: Information retrieval based integration of biophysical models for protein assembly selection

PubMed Central

Moal, Iain H.; Barradas-Bautista, Didier; Jiménez-García, Brian; Torchala, Mieczyslaw; van der Velde, Arjan; Vreven, Thom; Weng, Zhiping; Bates, Paul A.; Fernández-Recio, Juan

2018-01-01

Motivation In order to function, proteins frequently bind to one another and form 3D assemblies. Knowledge of the atomic details of these structures helps our understanding of how proteins work together, how mutations can lead to disease, and facilitates the designing of drugs which prevent or mimic the interaction. Results Atomic modeling of protein-protein interactions requires the selection of near-native structures from a set of docked poses based on their calculable properties. By considering this as an information retrieval problem, we have adapted methods developed for Internet search ranking and electoral voting into IRaPPA, a pipeline integrating biophysical properties. The approach enhances the identification of near-native structures when applied to four docking methods, resulting in a near-native appearing in the top 10 solutions for up to 50% of complexes benchmarked, and up to 70% in the top 100. Availability IRaPPA has been implemented in the SwarmDock server (http://bmm.crick.ac.uk/~SwarmDock/), pyDock server (http://life.bsc.es/pid/pydockrescoring/) and ZDOCK server (http://zdock.umassmed.edu/), with code available on request. PMID:28200016

Structural, mutagenic and in silico studies of xyloglucan fucosylation in Arabidopsis thaliana suggest a water-mediated mechanism

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

Urbanowicz, Breeanna R.; Bharadwaj, Vivek S.; Alahuhta, Markus

The mechanistic underpinnings of the complex process of plant polysaccharide biosynthesis are poorly understood, largely due to the resistance of glycosyltransferase (GT) enzymes to structural characterization. In Arabidopsis thaliana, a glycosyl transferase family 37 (GT37) fucosyltransferase-1 (AtFUT1) catalyzes the regiospecific transfer of terminal 1,2-fucosyl residues to xyloglucan side chains - a key step in the biosynthesis of fucosylated sidechains of galactoxyloglucan. We unravel the mechanistic basis for fucosylation by AtFUT1 with a multipronged approach involving protein expression, X-ray crystallography, mutagenesis experiments and molecular simulations. Mammalian cell culture expressions enable sufficient production of the enzyme for X-ray crystallography, which reveals themore » structural architecture of AtFUT1 in complex with bound donor and acceptor substrate analogs. Here, the lack of an appropriately positioned active site residue as a catalytic base leads us to propose an atypical water-mediated fucosylation mechanism facilitated by an H-bonded network, which is corroborated by mutagenesis experiments as well as detailed atomistic simulations.« less

Describing sequencing results of structural chromosome rearrangements with a suggested next-generation cytogenetic nomenclature.

PubMed

Ordulu, Zehra; Wong, Kristen E; Currall, Benjamin B; Ivanov, Andrew R; Pereira, Shahrin; Althari, Sara; Gusella, James F; Talkowski, Michael E; Morton, Cynthia C

2014-05-01

With recent rapid advances in genomic technologies, precise delineation of structural chromosome rearrangements at the nucleotide level is becoming increasingly feasible. In this era of "next-generation cytogenetics" (i.e., an integration of traditional cytogenetic techniques and next-generation sequencing), a consensus nomenclature is essential for accurate communication and data sharing. Currently, nomenclature for describing the sequencing data of these aberrations is lacking. Herein, we present a system called Next-Gen Cytogenetic Nomenclature, which is concordant with the International System for Human Cytogenetic Nomenclature (2013). This system starts with the alignment of rearrangement sequences by BLAT or BLAST (alignment tools) and arrives at a concise and detailed description of chromosomal changes. To facilitate usage and implementation of this nomenclature, we are developing a program designated BLA(S)T Output Sequence Tool of Nomenclature (BOSToN), a demonstrative version of which is accessible online. A standardized characterization of structural chromosomal rearrangements is essential both for research analyses and for application in the clinical setting. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

The role of uranium-arene bonding in H2O reduction catalysis

NASA Astrophysics Data System (ADS)

Halter, Dominik P.; Heinemann, Frank W.; Maron, Laurent; Meyer, Karsten

2018-03-01

The reactivity of uranium compounds towards small molecules typically occurs through stoichiometric rather than catalytic processes. Examples of uranium catalysts reacting with water are particularly scarce, because stable uranyl groups form that preclude the recovery of the uranium compound. Recently, however, an arene-anchored, electron-rich uranium complex has been shown to facilitate the electrocatalytic formation of H2 from H2O. Here, we present the precise role of uranium-arene δ bonding in intermediates of the catalytic cycle, as well as details of the atypical two-electron oxidative addition of H2O to the trivalent uranium catalyst. Both aspects were explored by synthesizing mid- and high-valent uranium-oxo intermediates and by performing comparative studies with a structurally related complex that cannot engage in δ bonding. The redox activity of the arene anchor and a covalent δ-bonding interaction with the uranium ion during H2 formation were supported by density functional theory analysis. Detailed insight into this catalytic system may inspire the design of ligands for new uranium catalysts.

Computerization of guidelines: a knowledge specification method to convert text to detailed decision tree for electronic implementation.

PubMed

Aguirre-Junco, Angel-Ricardo; Colombet, Isabelle; Zunino, Sylvain; Jaulent, Marie-Christine; Leneveut, Laurence; Chatellier, Gilles

2004-01-01

The initial step for the computerization of guidelines is the knowledge specification from the prose text of guidelines. We describe a method of knowledge specification based on a structured and systematic analysis of text allowing detailed specification of a decision tree. We use decision tables to validate the decision algorithm and decision trees to specify and represent this algorithm, along with elementary messages of recommendation. Edition tools are also necessary to facilitate the process of validation and workflow between expert physicians who will validate the specified knowledge and computer scientist who will encode the specified knowledge in a guide-line model. Applied to eleven different guidelines issued by an official agency, the method allows a quick and valid computerization and integration in a larger decision support system called EsPeR (Personalized Estimate of Risks). The quality of the text guidelines is however still to be developed further. The method used for computerization could help to define a framework usable at the initial step of guideline development in order to produce guidelines ready for electronic implementation.

GPU-accelerated FDTD modeling of radio-frequency field-tissue interactions in high-field MRI.

PubMed

Chi, Jieru; Liu, Feng; Weber, Ewald; Li, Yu; Crozier, Stuart

2011-06-01

The analysis of high-field RF field-tissue interactions requires high-performance finite-difference time-domain (FDTD) computing. Conventional CPU-based FDTD calculations offer limited computing performance in a PC environment. This study presents a graphics processing unit (GPU)-based parallel-computing framework, producing substantially boosted computing efficiency (with a two-order speedup factor) at a PC-level cost. Specific details of implementing the FDTD method on a GPU architecture have been presented and the new computational strategy has been successfully applied to the design of a novel 8-element transceive RF coil system at 9.4 T. Facilitated by the powerful GPU-FDTD computing, the new RF coil array offers optimized fields (averaging 25% improvement in sensitivity, and 20% reduction in loop coupling compared with conventional array structures of the same size) for small animal imaging with a robust RF configuration. The GPU-enabled acceleration paves the way for FDTD to be applied for both detailed forward modeling and inverse design of MRI coils, which were previously impractical.

Wavepacket dynamics and the multi-configurational time-dependent Hartree approach

NASA Astrophysics Data System (ADS)

Manthe, Uwe

2017-06-01

Multi-configurational time-dependent Hartree (MCTDH) based approaches are efficient, accurate, and versatile methods for high-dimensional quantum dynamics simulations. Applications range from detailed investigations of polyatomic reaction processes in the gas phase to high-dimensional simulations studying the dynamics of condensed phase systems described by typical solid state physics model Hamiltonians. The present article presents an overview of the different areas of application and provides a comprehensive review of the underlying theory. The concepts and guiding ideas underlying the MCTDH approach and its multi-mode and multi-layer extensions are discussed in detail. The general structure of the equations of motion is highlighted. The representation of the Hamiltonian and the correlated discrete variable representation (CDVR), which provides an efficient multi-dimensional quadrature in MCTDH calculations, are discussed. Methods which facilitate the calculation of eigenstates, the evaluation of correlation functions, and the efficient representation of thermal ensembles in MCTDH calculations are described. Different schemes for the treatment of indistinguishable particles in MCTDH calculations and recent developments towards a unified multi-layer MCTDH theory for systems including bosons and fermions are discussed.

MIST: An Open Source Environmental Modelling Programming Language Incorporating Easy to Use Data Parallelism.

NASA Astrophysics Data System (ADS)

Bellerby, Tim

2014-05-01

Model Integration System (MIST) is open-source environmental modelling programming language that directly incorporates data parallelism. The language is designed to enable straightforward programming structures, such as nested loops and conditional statements to be directly translated into sequences of whole-array (or more generally whole data-structure) operations. MIST thus enables the programmer to use well-understood constructs, directly relating to the mathematical structure of the model, without having to explicitly vectorize code or worry about details of parallelization. A range of common modelling operations are supported by dedicated language structures operating on cell neighbourhoods rather than individual cells (e.g.: the 3x3 local neighbourhood needed to implement an averaging image filter can be simply accessed from within a simple loop traversing all image pixels). This facility hides details of inter-process communication behind more mathematically relevant descriptions of model dynamics. The MIST automatic vectorization/parallelization process serves both to distribute work among available nodes and separately to control storage requirements for intermediate expressions - enabling operations on very large domains for which memory availability may be an issue. MIST is designed to facilitate efficient interpreter based implementations. A prototype open source interpreter is available, coded in standard FORTRAN 95, with tools to rapidly integrate existing FORTRAN 77 or 95 code libraries. The language is formally specified and thus not limited to FORTRAN implementation or to an interpreter-based approach. A MIST to FORTRAN compiler is under development and volunteers are sought to create an ANSI-C implementation. Parallel processing is currently implemented using OpenMP. However, parallelization code is fully modularised and could be replaced with implementations using other libraries. GPU implementation is potentially possible.

DNA damage may drive nucleosomal reorganization to facilitate damage detection

NASA Astrophysics Data System (ADS)

LeGresley, Sarah E.; Wilt, Jamie; Antonik, Matthew

2014-03-01

One issue in genome maintenance is how DNA repair proteins find lesions at rates that seem to exceed diffusion-limited search rates. We propose a phenomenon where DNA damage induces nucleosomal rearrangements which move lesions to potential rendezvous points in the chromatin structure. These rendezvous points are the dyad and the linker DNA between histones, positions in the chromatin which are more likely to be accessible by repair proteins engaged in a random search. The feasibility of this mechanism is tested by considering the statistical mechanics of DNA containing a single lesion wrapped onto the nucleosome. We consider lesions which make the DNA either more flexible or more rigid by modeling the lesion as either a decrease or an increase in the bending energy. We include this energy in a partition function model of nucleosome breathing. Our results indicate that the steady state for a breathing nucleosome will most likely position the lesion at the dyad or in the linker, depending on the energy of the lesion. A role for DNA binding proteins and chromatin remodelers is suggested based on their ability to alter the mechanical properties of the DNA and DNA-histone binding, respectively. We speculate that these positions around the nucleosome potentially serve as rendezvous points where DNA lesions may be encountered by repair proteins which may be sterically hindered from searching the rest of the nucleosomal DNA. The strength of the repositioning is strongly dependent on the structural details of the DNA lesion and the wrapping and breathing of the nucleosome. A more sophisticated evaluation of this proposed mechanism will require detailed information about breathing dynamics, the structure of partially wrapped nucleosomes, and the structural properties of damaged DNA.

An interdisciplinary team communication framework and its application to healthcare 'e-teams' systems design

PubMed Central

2009-01-01

Background There are few studies that examine the processes that interdisciplinary teams engage in and how we can design health information systems (HIS) to support those team processes. This was an exploratory study with two purposes: (1) To develop a framework for interdisciplinary team communication based on structures, processes and outcomes that were identified as having occurred during weekly team meetings. (2) To use the framework to guide 'e-teams' HIS design to support interdisciplinary team meeting communication. Methods An ethnographic approach was used to collect data on two interdisciplinary teams. Qualitative content analysis was used to analyze the data according to structures, processes and outcomes. Results We present details for team meta-concepts of structures, processes and outcomes and the concepts and sub concepts within each meta-concept. We also provide an exploratory framework for interdisciplinary team communication and describe how the framework can guide HIS design to support 'e-teams'. Conclusion The structures, processes and outcomes that describe interdisciplinary teams are complex and often occur in a non-linear fashion. Electronic data support, process facilitation and team video conferencing are three HIS tools that can enhance team function. PMID:19754966

An interdisciplinary team communication framework and its application to healthcare 'e-teams' systems design.

PubMed

Kuziemsky, Craig E; Borycki, Elizabeth M; Purkis, Mary Ellen; Black, Fraser; Boyle, Michael; Cloutier-Fisher, Denise; Fox, Lee Ann; MacKenzie, Patricia; Syme, Ann; Tschanz, Coby; Wainwright, Wendy; Wong, Helen

2009-09-15

There are few studies that examine the processes that interdisciplinary teams engage in and how we can design health information systems (HIS) to support those team processes. This was an exploratory study with two purposes: (1) To develop a framework for interdisciplinary team communication based on structures, processes and outcomes that were identified as having occurred during weekly team meetings. (2) To use the framework to guide 'e-teams' HIS design to support interdisciplinary team meeting communication. An ethnographic approach was used to collect data on two interdisciplinary teams. Qualitative content analysis was used to analyze the data according to structures, processes and outcomes. We present details for team meta-concepts of structures, processes and outcomes and the concepts and sub concepts within each meta-concept. We also provide an exploratory framework for interdisciplinary team communication and describe how the framework can guide HIS design to support 'e-teams'. The structures, processes and outcomes that describe interdisciplinary teams are complex and often occur in a non-linear fashion. Electronic data support, process facilitation and team video conferencing are three HIS tools that can enhance team function.

Structural and evolutionary analysis of Leishmania Alba proteins.

PubMed

da Costa, Kauê Santana; Galúcio, João Marcos Pereira; Leonardo, Elvis Santos; Cardoso, Guelber; Leal, Élcio; Conde, Guilherme; Lameira, Jerônimo

2017-10-01

The Alba superfamily proteins share a common RNA-binding domain. These proteins participate in a variety of regulatory pathways by controlling developmental gene expression. They also interact with ribosomal subunits, translation factors, and other RNA-binding proteins. The Leishmania infantum genome encodes two Alba-domain proteins, LiAlba1 and LiAlba3. In this work, we used homology modeling, protein-protein docking, and molecular dynamics (MD) simulations to explore the details of the Alba1-Alba3-RNA complex from Leishmania infantum at the molecular level. In addition, we compared the structure of LiAlba3 with the human ribonuclease P component, Rpp20. We also mapped the ligand-binding residues on the Alba3 surface to analyze its druggability and performed mutational analyses in Alba3 using alanine scanning to identify residues involved in its function and structural stability. These results suggest that the RGG-box motif of LiAlba1 is important for protein function and stability. Finally, we discuss the function of Alba proteins in the context of pathogen adaptation to host cells. The data provided herein will facilitate further translational research regarding Alba structure and function. Copyright © 2017 Elsevier B.V. All rights reserved.

Protein arginine deiminase 2 binds calcium in an ordered fashion: Implications for inhibitor design

DOE PAGES

Slade, Daniel J.; Fang, Pengfei; Dreyton, Christina J.; ...

2015-01-26

Protein arginine deiminases (PADs) are calcium-dependent histone-modifying enzymes whose activity is dysregulated in inflammatory diseases and cancer. PAD2 functions as an Estrogen Receptor (ER) coactivator in breast cancer cells via the citrullination of histone tail arginine residues at ER binding sites. Although an attractive therapeutic target, the mechanisms that regulate PAD2 activity are largely unknown, especially the detailed role of how calcium facilitates enzyme activation. To gain insights into these regulatory processes, we determined the first structures of PAD2 (27 in total), and through calcium-titrations by X-ray crystallography, determined the order of binding and affinity for the six calcium ionsmore » that bind and activate this enzyme. These structures also identified several PAD2 regulatory elements, including a calcium switch that controls proper positioning of the catalytic cysteine residue, and a novel active site shielding mechanism. Additional biochemical and mass-spectrometry-based hydrogen/deuterium exchange studies support these structural findings. The identification of multiple intermediate calcium-bound structures along the PAD2 activation pathway provides critical insights that will aid the development of allosteric inhibitors targeting the PADs.« less

Protein Arginine Deiminase 2 Binds Calcium in an Ordered Fashion: Implications for Inhibitor Design

PubMed Central

2015-01-01

Protein arginine deiminases (PADs) are calcium-dependent histone-modifying enzymes whose activity is dysregulated in inflammatory diseases and cancer. PAD2 functions as an Estrogen Receptor (ER) coactivator in breast cancer cells via the citrullination of histone tail arginine residues at ER binding sites. Although an attractive therapeutic target, the mechanisms that regulate PAD2 activity are largely unknown, especially the detailed role of how calcium facilitates enzyme activation. To gain insights into these regulatory processes, we determined the first structures of PAD2 (27 in total), and through calcium-titrations by X-ray crystallography, determined the order of binding and affinity for the six calcium ions that bind and activate this enzyme. These structures also identified several PAD2 regulatory elements, including a calcium switch that controls proper positioning of the catalytic cysteine residue, and a novel active site shielding mechanism. Additional biochemical and mass-spectrometry-based hydrogen/deuterium exchange studies support these structural findings. The identification of multiple intermediate calcium-bound structures along the PAD2 activation pathway provides critical insights that will aid the development of allosteric inhibitors targeting the PADs. PMID:25621824

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.

Ligand and structure-based methodologies for the prediction of the activity of G protein-coupled receptor ligands

NASA Astrophysics Data System (ADS)

Costanzi, Stefano; Tikhonova, Irina G.; Harden, T. Kendall; Jacobson, Kenneth A.

2009-11-01

Accurate in silico models for the quantitative prediction of the activity of G protein-coupled receptor (GPCR) ligands would greatly facilitate the process of drug discovery and development. Several methodologies have been developed based on the properties of the ligands, the direct study of the receptor-ligand interactions, or a combination of both approaches. Ligand-based three-dimensional quantitative structure-activity relationships (3D-QSAR) techniques, not requiring knowledge of the receptor structure, have been historically the first to be applied to the prediction of the activity of GPCR ligands. They are generally endowed with robustness and good ranking ability; however they are highly dependent on training sets. Structure-based techniques generally do not provide the level of accuracy necessary to yield meaningful rankings when applied to GPCR homology models. However, they are essentially independent from training sets and have a sufficient level of accuracy to allow an effective discrimination between binders and nonbinders, thus qualifying as viable lead discovery tools. The combination of ligand and structure-based methodologies in the form of receptor-based 3D-QSAR and ligand and structure-based consensus models results in robust and accurate quantitative predictions. The contribution of the structure-based component to these combined approaches is expected to become more substantial and effective in the future, as more sophisticated scoring functions are developed and more detailed structural information on GPCRs is gathered.

The TEDxLSU Student Creative Communications Team: Integrating High-Impact Practices to Increase Engagement, Facilitate Deep Learning, and Advance Communication Skills

ERIC Educational Resources Information Center

Burdette, Rebecca; Galeucia, Annemarie; Liggett, Sarah; Thompson, Melissa

2016-01-01

This article provides background on Louisiana State University's Communication across the Curriculum (CxC) program and details the history and logistics of its experiential learning and community outreach event--TEDxLSU. In particular, the authors provide details on the Student Creative Communications Team (SCCT) which conceptualizes, plans, and…

Digital dissection - using contrast-enhanced computed tomography scanning to elucidate hard- and soft-tissue anatomy in the Common Buzzard Buteo buteo.

PubMed

Lautenschlager, Stephan; Bright, Jen A; Rayfield, Emily J

2014-04-01

Gross dissection has a long history as a tool for the study of human or animal soft- and hard-tissue anatomy. However, apart from being a time-consuming and invasive method, dissection is often unsuitable for very small specimens and often cannot capture spatial relationships of the individual soft-tissue structures. The handful of comprehensive studies on avian anatomy using traditional dissection techniques focus nearly exclusively on domestic birds, whereas raptorial birds, and in particular their cranial soft tissues, are essentially absent from the literature. Here, we digitally dissect, identify, and document the soft-tissue anatomy of the Common Buzzard (Buteo buteo) in detail, using the new approach of contrast-enhanced computed tomography using Lugol's iodine. The architecture of different muscle systems (adductor, depressor, ocular, hyoid, neck musculature), neurovascular, and other soft-tissue structures is three-dimensionally visualised and described in unprecedented detail. The three-dimensional model is further presented as an interactive PDF to facilitate the dissemination and accessibility of anatomical data. Due to the digital nature of the data derived from the computed tomography scanning and segmentation processes, these methods hold the potential for further computational analyses beyond descriptive and illustrative proposes. © 2013 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.

Observations of Building Performance under Combined Wind and Surge Loading from Hurricane Harvey

NASA Astrophysics Data System (ADS)

Lombardo, F.; Roueche, D. B.; Krupar, R. J.; Smith, D. J.; Soto, M. G.

2017-12-01

Hurricane Harvey struck the Texas coastline on August 25, 2017, as a Category 4 hurricane - the first major hurricane to reach the US in twelve years. Wind gusts over 130 mph and storm surge as high as 12.5 ft caused widespread damage to buildings and critical infrastructure in coastal communities including Rockport, Fulton, Port Aransas and Aransas Pass. This study presents the methodology and preliminary observations of a coordinated response effort to document residential building performance under wind and storm surge loading. Over a twelve day survey period the study team assessed the performance of more than 1,000 individual, geo-located residential buildings. Assessments were logged via a smartphone application to facilitate rapid collection and collation of geotagged photographs, building attributes and structural details, and structural damage observations. Detailed assessments were also made of hazard intensity, specifically storm surge heights and both wind speed and direction indicators. Preliminary observations and findings will be presented, showing strong gradients in damage between inland and coastal regions of the affected areas that may be due in part to enhanced individual loading effects of wind and storm surge and potentially joint-hazard loading effects. Contributing factors to the many cases of disproportionate damage observed in close proximity will also be discussed. Ongoing efforts to relate building damage to near-surface hazard measurements (e.g., radar, anemometry) in close proximity will also be described.

Structural and dynamic properties of the C-terminal region of the Escherichia coli RNA chaperone Hfq: integrative experimental and computational studies.

PubMed

Wen, Bin; Wang, Weiwei; Zhang, Jiahai; Gong, Qingguo; Shi, Yunyu; Wu, Jihui; Zhang, Zhiyong

2017-08-09

In Escherichia coli, hexameric Hfq is an important RNA chaperone that facilitates small RNA-mediated post-transcriptional regulation. The Hfq monomer consists of an evolutionarily conserved Sm domain (residues 1-65) and a flexible C-terminal region (residues 66-102). It has been recognized that the existence of the C-terminal region is important for the function of Hfq, but its detailed structural and dynamic properties remain elusive due to its disordered nature. In this work, using integrative experimental techniques, such as nuclear magnetic resonance spectroscopy and small-angle X-ray scattering, as well as multi-scale computational simulations, new insights into the structure and dynamics of the C-terminal region in the context of the Hfq hexamer are provided. Although the C-terminal region is intrinsically disordered, some residues (83-86) are motionally restricted. The hexameric core may affect the secondary structure propensity of the C-terminal region, due to transient interactions between them. The residues at the rim and the proximal side of the core have significantly more transient contacts with the C-terminal region than those residues at the distal side, which may facilitate the function of the C-terminal region in the release of double-stranded RNAs and the cycling of small non-coding RNAs. Structure ensembles constructed by fitting the experimental data also support that the C-terminal region prefers to locate at the proximal side. From multi-scale simulations, we propose that the C-terminal region may play a dual role of steric effect (especially at the proximal side) and recruitment (at the both sides) in the binding process of RNA substrates. Interestingly, we have found that these motionally restricted residues may serve as important binding sites for the incoming RNAs that is probably driven by favorable electrostatic interactions. These integrative studies may aid in our understanding of the functional role of the C-terminal region of Hfq.

The characteristics of effective secondary math and science instructional facilitators and the necessary support structures as perceived by practitioners and principals

NASA Astrophysics Data System (ADS)

Mahagan, Vikki Lynn

Instructional facilitators are known by a variety of titles depending on the school district in which they are employed. They are sometimes called instructional coaches, teacher leaders, lead teachers, and instructional specialist (Denton & Hasbrouck, 2009). Throughout this study, the title instructional facilitator was used and will refer to secondary math or science instructional facilitators who are housed at least one day per week on a campus. This study is a mixed-methods descriptive study which has identified character traits, specials skill, and talents possessed by effective secondary math and science instructional facilitators as perceived by practicing facilitators and principals and assistant principals who work along side instructional facilitators. Specific job training to help ensure the success of a facilitator was identified as viewed by both facilitators and principals. Additionally, this study compared the perceptions of practicing facilitators and principals to determine if significant differences exist with respect to perceptions of staff development opportunities, support structures, and resources available for instructional facilitators.

Interdomain Contacts Control Native State Switching of RfaH on a Dual-Funneled Landscape

PubMed Central

Ramírez-Sarmiento, César A.; Noel, Jeffrey K.; Valenzuela, Sandro L.; Artsimovitch, Irina

2015-01-01

RfaH is a virulence factor from Escherichia coli whose C-terminal domain (CTD) undergoes a dramatic α-to-β conformational transformation. The CTD in its α-helical fold is stabilized by interactions with the N-terminal domain (NTD), masking an RNA polymerase binding site until a specific recruitment site is encountered. Domain dissociation is triggered upon binding to DNA, allowing the NTD to interact with RNA polymerase to facilitate transcription while the CTD refolds into the β-barrel conformation that interacts with the ribosome to activate translation. However, structural details of this transformation process in the context of the full protein remain to be elucidated. Here, we explore the mechanism of the α-to-β conformational transition of RfaH in the full-length protein using a dual-basin structure-based model. Our simulations capture several features described experimentally, such as the requirement of disruption of interdomain contacts to trigger the α-to-β transformation, confirms the roles of previously indicated residues E48 and R138, and suggests a new important role for F130, in the stability of the interdomain interaction. These native basins are connected through an intermediate state that builds up upon binding to the NTD and shares features from both folds, in agreement with previous in silico studies of the isolated CTD. We also examine the effect of RNA polymerase binding on the stabilization of the β fold. Our study shows that native-biased models are appropriate for interrogating the detailed mechanisms of structural rearrangements during the dramatic transformation process of RfaH. PMID:26230837

Tandem SUMO fusion vectors for improving soluble protein expression and purification.

PubMed

Guerrero, Fernando; Ciragan, Annika; Iwaï, Hideo

2015-12-01

Availability of highly purified proteins in quantity is crucial for detailed biochemical and structural investigations. Fusion tags are versatile tools to facilitate efficient protein purification and to improve soluble overexpression of proteins. Various purification and fusion tags have been widely used for overexpression in Escherichia coli. However, these tags might interfere with biological functions and/or structural investigations of the protein of interest. Therefore, an additional purification step to remove fusion tags by proteolytic digestion might be required. Here, we describe a set of new vectors in which yeast SUMO (SMT3) was used as the highly specific recognition sequence of ubiquitin-like protease 1, together with other commonly used solubility enhancing proteins, such as glutathione S-transferase, maltose binding protein, thioredoxin and trigger factor for optimizing soluble expression of protein of interest. This tandem SUMO (T-SUMO) fusion system was tested for soluble expression of the C-terminal domain of TonB from different organisms and for the antiviral protein scytovirin. Copyright © 2015 Elsevier Inc. All rights reserved.

The ESFRI Instruct Core Centre Frankfurt: automated high-throughput crystallization suited for membrane proteins and more.

PubMed

Thielmann, Yvonne; Koepke, Juergen; Michel, Hartmut

2012-06-01

Structure determination of membrane proteins and membrane protein complexes is still a very challenging field. To facilitate the work on membrane proteins the Core Centre follows a strategy that comprises four labs of protein analytics and crystal handling, covering mass spectrometry, calorimetry, crystallization and X-ray diffraction. This general workflow is presented and a capacity of 20% of the operating time of all systems is provided to the European structural biology community within the ESFRI Instruct program. A description of the crystallization service offered at the Core Centre is given with detailed information on screening strategy, screens used and changes to adapt high throughput for membrane proteins. Our aim is to constantly develop the Core Centre towards the usage of more efficient methods. This strategy might also include the ability to automate all steps from crystallization trials to crystal screening; here we look ahead how this aim might be realized at the Core Centre.

Games among relatives revisited.

PubMed

Allen, Benjamin; Nowak, Martin A

2015-08-07

We present a simple model for the evolution of social behavior in family-structured, finite sized populations. Interactions are represented as evolutionary games describing frequency-dependent selection. Individuals interact more frequently with siblings than with members of the general population, as quantified by an assortment parameter r, which can be interpreted as "relatedness". Other models, mostly of spatially structured populations, have shown that assortment can promote the evolution of cooperation by facilitating interaction between cooperators, but this effect depends on the details of the evolutionary process. For our model, we find that sibling assortment promotes cooperation in stringent social dilemmas such as the Prisoner's Dilemma, but not necessarily in other situations. These results are obtained through straightforward calculations of changes in gene frequency. We also analyze our model using inclusive fitness. We find that the quantity of inclusive fitness does not exist for general games. For special games, where inclusive fitness exists, it provides less information than the straightforward analysis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Reminiscences of research on the chemistry and biology of natural sterols in insects, plants and humans.

PubMed

Ikekawa, Nobuo; Fujimoto, Yoshinori; Ishiguro, Masaji

2013-01-01

Natural sterols often occur as a heterogeneous mixture of homologs, which had disturbed the progress of steroid research. Development and application of GC methodology overcame this difficulty and enabled us to obtain detailed sterol profiles. Together, fine synthesis of stereo-defined isomers and homologs of steroids having oxygenated side chains allowed us to compare them with natural samples as well as to investigate structure-activity relationship. Advance of HPLC technology also facilitated the determination of the stereochemical structure of naturally occurring steroidal compounds, which were obtained only in minute amounts. This review highlights three topics out of our steroid research that have been performed mainly at Tokyo Institute of Technology around 1970-1990. These are sterol metabolism in insects focusing on the mechanism of the conversion of plant sterols to cholesterol and ecdysone biosynthesis, the synthesis and biochemical research of active forms of vitamin D3 derivatives, and the synthesis and microanalysis of plant hormone brassinosteroids.

LINCing complex functions at the nuclear envelope

PubMed Central

Rothballer, Andrea; Schwartz, Thomas U.; Kutay, Ulrike

2013-01-01

Linker of nucleoskeleton and cytoskeleton (LINC) complexes span the double membrane of the nuclear envelope (NE) and physically connect nuclear structures to cytoskeletal elements. LINC complexes are envisioned as force transducers in the NE, which facilitate processes like nuclear anchorage and migration, or chromosome movements. The complexes are built from members of two evolutionary conserved families of transmembrane (TM) proteins, the SUN (Sad1/UNC-84) domain proteins in the inner nuclear membrane (INM) and the KASH (Klarsicht/ANC-1/SYNE homology) domain proteins in the outer nuclear membrane (ONM). In the lumen of the NE, the SUN and KASH domains engage in an intimate assembly to jointly form a NE bridge. Detailed insights into the molecular architecture and atomic structure of LINC complexes have recently revealed the molecular basis of nucleo-cytoskeletal coupling. They bear important implications for LINC complex function and suggest new potential and as yet unexplored roles, which the complexes may play in the cell. PMID:23324460

A national facility for biological cryo-electron microscopy

PubMed Central

Saibil, Helen R.; Grünewald, Kay; Stuart, David I.

2015-01-01

Three-dimensional electron microscopy is an enormously powerful tool for structural biologists. It is now able to provide an understanding of the molecular machinery of cells, disease processes and the actions of pathogenic organisms from atomic detail through to the cellular context. However, cutting-edge research in this field requires very substantial resources for equipment, infrastructure and expertise. Here, a brief overview is provided of the plans for a UK national three-dimensional electron-microscopy facility for integrated structural biology to enable internationally leading research on the machinery of life. State-of-the-art equipment operated with expert support will be provided, optimized for both atomic-level single-particle analysis of purified macromolecules and complexes and for tomography of cell sections. The access to and organization of the facility will be modelled on the highly successful macromolecular crystallography (MX) synchrotron beamlines, and will be embedded at the Diamond Light Source, facilitating the development of user-friendly workflows providing near-real-time experimental feedback. PMID:25615867

Binding Modes of Thioflavin T Molecules to Prion Peptide Assemblies Identified by Using Scanning Tunneling Microscopy

PubMed Central

2011-01-01

The widely used method to monitor the aggregation process of amyloid peptide is thioflavin T (ThT) assay, while the detailed molecular mechanism is still not clear. In this work, we report here the direct identification of the binding modes of ThT molecules with the prion peptide GNNQQNY by using scanning tunneling microscopy (STM). The assembly structures of GNNQQNY were first observed by STM on a graphite surface, and the introduction of ThT molecules to the surface facilitated the STM observations of the adsorption conformations of ThT with peptide strands. ThT molecules are apt to adsorb on the peptide assembly with β-sheet structure and oriented parallel with the peptide strands adopting four different binding modes. This effort could benefit the understanding of the mechanisms of the interactions between labeling species or inhibitory ligands and amyloid peptides, which is keenly needed for developing diagnostic and therapeutic approaches. PMID:22778872

Speckle reduction in optical coherence tomography using two-step iteration method (Conference Presentation)

NASA Astrophysics Data System (ADS)

Wang, Xianghong; Liu, Xinyu; Wang, Nanshuo; Yu, Xiaojun; Bo, En; Chen, Si; Liu, Linbo

2017-02-01

Optical coherence tomography (OCT) provides high resolution and cross-sectional images of biological tissue and is widely used for diagnosis of ocular diseases. However, OCT images suffer from speckle noise, which typically considered as multiplicative noise in nature, reducing the image resolution and contrast. In this study, we propose a two-step iteration (TSI) method to suppress those noises. We first utilize augmented Lagrange method to recover a low-rank OCT image and remove additive Gaussian noise, and then employ the simple and efficient split Bregman method to solve the Total-Variation Denoising model. We validated such proposed method using images of swine, rabbit and human retina. Results demonstrate that our TSI method outperforms the other popular methods in achieving higher peak signal-to-noise ratio (PSNR) and structure similarity (SSIM) while preserving important structural details, such as tiny capillaries and thin layers in retinal OCT images. In addition, the results of our TSI method show clearer boundaries and maintains high image contrast, which facilitates better image interpretations and analyses.

A comprehensive review on pre-treatment strategy for lignocellulosic food industry waste: Challenges and opportunities.

PubMed

Ravindran, Rajeev; Jaiswal, Amit Kumar

2016-01-01

Lignocellulose is a generic term used to describe plant biomass. It is the most abundant renewable carbon resource in the world and is mainly composed of lignin, cellulose and hemicelluloses. Most of the food and food processing industry waste are lignocellulosic in nature with a global estimate of up to 1.3 billion tons/year. Lignocellulose, on hydrolysis, releases reducing sugars which is used for the production of bioethanol, biogas, organic acids, enzymes and biosorbents. However, structural conformation, high lignin content and crystalline cellulose hinder its use for value addition. Pre-treatment strategies facilitate the exposure of more cellulose and hemicelluloses for enzymatic hydrolysis. The present article confers about the structure of lignocellulose and how it influences enzymatic degradation emphasising the need for pre-treatments along with a comprehensive analysis and categorisation of the same. Finally, this article concludes with a detailed discussion on microbial/enzymatic inhibitors that arise post pre-treatment and strategies to eliminate them. Copyright © 2015 Elsevier Ltd. All rights reserved.

New Algorithm to Enable Construction and Display of 3D Structures from Scanning Probe Microscopy Images Acquired Layer-by-Layer.

PubMed

Deng, William Nanqiao; Wang, Shuo; Ventrici de Souza, Joao; Kuhl, Tonya L; Liu, Gang-Yu

2018-06-25

Scanning probe microscopy (SPM), such as atomic force microscopy (AFM), is widely known for high-resolution imaging of surface structures and nanolithography in two dimensions (2D), providing important physical insights into surface science and material science. This work reports a new algorithm to enable construction and display of layer-by-layer 3D structures from SPM images. The algorithm enables alignment of SPM images acquired during layer-by-layer deposition and removal of redundant features and faithfully constructs the deposited 3D structures. The display uses a "see-through" strategy to enable the structure of each layer to be visible. The results demonstrate high spatial accuracy as well as algorithm versatility; users can set parameters for reconstruction and display as per image quality and research needs. To the best of our knowledge, this method represents the first report to enable SPM technology for 3D imaging construction and display. The detailed algorithm is provided to facilitate usage of the same approach in any SPM software. These new capabilities support wide applications of SPM that require 3D image reconstruction and display, such as 3D nanoprinting and 3D additive and subtractive manufacturing and imaging.

Structural basis of transport function in major facilitator superfamily protein from Trichoderma harzianum.

PubMed

Chaudhary, Nitika; Sandhu, Padmani; Ahmed, Mushtaq; Akhter, Yusuf

2017-02-01

Trichothecenes are the sesquiterpenes secreted by Trichoderma spp. residing in the rhizosphere. These compounds have been reported to act as plant growth promoters and bio-control agents. The structural knowledge for the transporter proteins of their efflux remained limited. In this study, three-dimensional structure of Thmfs1 protein, a trichothecene transporter from Trichoderma harzianum, was homology modelled and further Molecular Dynamics (MD) simulations were used to decipher its mechanism. Fourteen transmembrane helices of Thmfs1 protein are observed contributing to an inward-open conformation. The transport channel and ligand binding sites in Thmfs1 are identified based on heuristic, iterative algorithm and structural alignment with homologous proteins. MD simulations were performed to reveal the differential structural behaviour occurring in the ligand free and ligand bound forms. We found that two discrete trichothecene binding sites are located on either side of the central transport tunnel running from the cytoplasmic side to the extracellular side across the Thmfs1 protein. Detailed analysis of the MD trajectories showed an alternative access mechanism between N and C-terminal domains contributing to its function. These results also demonstrate that the transport of trichodermin occurs via hopping mechanism in which the substrate molecule jumps from one binding site to another lining the transport tunnel. Copyright © 2016 Elsevier B.V. All rights reserved.

Cryo-EM structure of the spinach chloroplast ribosome reveals the location of plastid-specific ribosomal proteins and extensions

PubMed Central

Graf, Michael; Arenz, Stefan; Huter, Paul; Dönhöfer, Alexandra; Nováček, Jiří

2017-01-01

Abstract Ribosomes are the protein synthesizing machines of the cell. Recent advances in cryo-EM have led to the determination of structures from a variety of species, including bacterial 70S and eukaryotic 80S ribosomes as well as mitoribosomes from eukaryotic mitochondria, however, to date high resolution structures of plastid 70S ribosomes have been lacking. Here we present a cryo-EM structure of the spinach chloroplast 70S ribosome, with an average resolution of 5.4 Å for the small 30S subunit and 3.6 Å for the large 50S ribosomal subunit. The structure reveals the location of the plastid-specific ribosomal proteins (RPs) PSRP1, PSRP4, PSRP5 and PSRP6 as well as the numerous plastid-specific extensions of the RPs. We discover many features by which the plastid-specific extensions stabilize the ribosome via establishing additional interactions with surrounding ribosomal RNA and RPs. Moreover, we identify a large conglomerate of plastid-specific protein mass adjacent to the tunnel exit site that could facilitate interaction of the chloroplast ribosome with the thylakoid membrane and the protein-targeting machinery. Comparing the Escherichia coli 70S ribosome with that of the spinach chloroplast ribosome provides detailed insight into the co-evolution of RP and rRNA. PMID:27986857

Therapeutic risk management of the suicidal patient: augmenting clinical suicide risk assessment with structured instruments.

PubMed

Homaifar, Beeta; Matarazzo, Bridget; Wortzel, Hal S

2013-09-01

This column is the second in a series presenting a model for therapeutic risk management of the suicidal patient. As discussed in the first part of the series, the model involves several elements including augmenting clinical risk assessment with structured instruments, stratifying risk in terms of both severity and temporality, and developing and documenting a safety plan. This column explores in more detail how to augment clinical risk assessment with structured instruments. Unstructured clinical interviews have the potential to miss important aspects of suicide risk assessment. By augmenting the free-form clinical interview with structured instruments that demonstrate reliability and validity, a more nuanced and multifaceted approach to suicide risk assessment is achieved. Incorporating structured instruments into practice also serves a medicolegal function, since these instruments may become a living part of the medical record, establishing baseline levels of suicidal thoughts and behaviors and facilitating future clinical determinations regarding safety needs. We describe several instruments used in a multidisciplinary suicide consultation service, each of which has demonstrated relevance to suicide risk assessment and screening, ease of administration, and strong psychometric properties. In addition, we emphasize the importance of viewing suicide risk assessment as an ongoing process rather than as a singular event. Finally, we discuss special considerations in the evolving practice of risk assessment.

Structural evolution dynamics in fusion of sumanenes and corannulenes: defects formation and self-healing mechanism

NASA Astrophysics Data System (ADS)

Sorkin, Anastassia; Su, Haibin

2018-06-01

The fusion processes of structures consisting of various combinations between sumanene and corannulene, leading to the formation of graphene nanoribbons (GNRs) under heating are simulated by density-functional-based tight-binding molecular dynamics. Distinct stages are unraveled in the course of GNR formation. Firstly, the carbon fragments coalescence into highly strained framework. Secondly, structural reconstruction invokes breaking most strained bonds to form a GNR structure containing numerous defects. Lastly, defects are remedied by the delicate ‘edge-facilitated self-healing’ process through two synergized edge-related effects: elevated mobility of defects and promoted structure reconstructions owing to the remarkable dynamics associated with edges. Importantly, detailed dynamics in the course of forming GNRs with defects and grain boundaries simulated in this work is valuable to provide better understanding at the atomistic scale of defect formation as well as self-healing in the context of the sp2 carbon network. In particular, edges play important roles in not only generating Stone–Wales (SW), 5-8-5 types of defects, 8-5-5-8 and pentagon–heptagon grain boundaries. In addition, our simulations predict the existence of one novel defect, coined as the Inverse SW defect, which is to be confirmed in future experimental studies. This study of dynamic structural evolution reveals that edges are prone to intrinsic and extrinsic modifications such as atomic-scale defects, structural distortions and inhomogeneity.

Environmental Enhancements and Navigation Infrastructure: A Study of Existing Practices, Innovative Ideas, Impediments, and Research Needs

DTIC Science & Technology

2011-07-01

velocity/substrate Excavate back channels in river systems Piers & Wharves Design hard structures to facilitate better seaweed recruitment...allows vegetative colonization of areas beneath the structures P Design hard structures to facilitate better seaweed recruitment I Provide

Determinants of Electricity Consumption Intensity in China: Analysis of Cities at Subprovince and Prefecture Levels in 2009

PubMed Central

Xia, X. H.; Hu, Yi

2012-01-01

China has experienced great social and economic vicissitudes that caused the vast complexity and uncertainty for electricity consumption. This paper attempts to identify the main determinants of the electricity consumption intensity by using the data from Chinese cities at subprovince and prefecture levels in 2009. The key category factors, including urban morphology, industrial structure, regulation context, urbanization degree, price, natural condition, and resource endowment, are abstracted and the influence of these determinants is evaluated by adopting the finite mixture models. The variation of each determinant across regions, the comparative weights of all the factors, and the detailed classifications of the cities are reported for facilitating the understanding of electricity consumption in China. The corresponding policies for electricity administration are addressed as well. PMID:22927781

Robotic inspection of fiber reinforced composites using phased array UT

NASA Astrophysics Data System (ADS)

Stetson, Jeffrey T.; De Odorico, Walter

2014-02-01

Ultrasound is the current NDE method of choice to inspect large fiber reinforced airframe structures. Over the last 15 years Cartesian based scanning machines using conventional ultrasound techniques have been employed by all airframe OEMs and their top tier suppliers to perform these inspections. Technical advances in both computing power and commercially available, multi-axis robots now facilitate a new generation of scanning machines. These machines use multiple end effector tools taking full advantage of phased array ultrasound technologies yielding substantial improvements in inspection quality and productivity. This paper outlines the general architecture for these new robotic scanning systems as well as details the variety of ultrasonic techniques available for use with them including advances such as wide area phased array scanning and sound field adaptation for non-flat, non-parallel surfaces.

Maturity of hospital information systems: Most important influencing factors.

PubMed

Vidal Carvalho, João; Rocha, Álvaro; Abreu, António

2017-07-01

Maturity models facilitate organizational management, including information systems management, with hospital organizations no exception. This article puts forth a study carried out with a group of experts in the field of hospital information systems management with a view to identifying the main influencing factors to be included in an encompassing maturity model for hospital information systems management. This study is based on the results of a literature review, which identified maturity models in the health field and relevant influencing factors. The development of this model is justified to the extent that the available maturity models for the hospital information systems management field reveal multiple limitations, including lack of detail, absence of tools to determine their maturity and lack of characterization for stages of maturity structured by different influencing factors.

BIOSPIDA: A Relational Database Translator for NCBI.

PubMed

Hagen, Matthew S; Lee, Eva K

2010-11-13

As the volume and availability of biological databases continue widespread growth, it has become increasingly difficult for research scientists to identify all relevant information for biological entities of interest. Details of nucleotide sequences, gene expression, molecular interactions, and three-dimensional structures are maintained across many different databases. To retrieve all necessary information requires an integrated system that can query multiple databases with minimized overhead. This paper introduces a universal parser and relational schema translator that can be utilized for all NCBI databases in Abstract Syntax Notation (ASN.1). The data models for OMIM, Entrez-Gene, Pubmed, MMDB and GenBank have been successfully converted into relational databases and all are easily linkable helping to answer complex biological questions. These tools facilitate research scientists to locally integrate databases from NCBI without significant workload or development time.

History and Evolution of Active Learning Spaces

ERIC Educational Resources Information Center

Beichner, Robert J.

2014-01-01

This chapter examines active learning spaces as they have developed over the years. Consistently well-designed classrooms can facilitate active learning even though the details of implementing pedagogies may differ.

Fine-tuning of microsolvation and hydrogen bond interaction regulates substrate channelling in the course of flavonoid biosynthesis.

PubMed

Diharce, Julien; Golebiowski, Jérôme; Fiorucci, Sébastien; Antonczak, Serge

2016-04-21

In the course of metabolite formation, some multienzymatic edifices, the so-called metabolon, are formed and lead to a more efficient production of these natural compounds. One of the major features of these enzyme complexes is the facilitation of direct transfer of the metabolite between enzyme active sites by substrate channelling. Biophysical insights into substrate channelling remain scarce because the transient nature of these macromolecular complexes prevents the observation of high resolution structures. Here, using molecular modelling, we describe the substrate channelling of a flavonoid compound between DFR (dihydroflavonol-4-reductase) and LAR (leucoanthocyanidin reductase). The simulation presents crucial details concerning the kinetic, thermodynamic, and structural aspects of this diffusion. The formation of the DFR-LAR complex leads to the opening of the DFR active site giving rise to a facilitated diffusion, in about 1 μs, of the DFR product towards LAR cavity. The theoretically observed substrate channelling is supported experimentally by the fact that this metabolite, i.e. the product of the DFR enzyme, is not stable in the media. Moreover, along this path, the influence of the solvent is crucial. The metabolite remains close to the surface of the complex avoiding full solvation. In addition, when the dynamic behaviour of the system leads to a loss of interaction between the metabolite and the enzymes, water molecules through bridging H-bonds prevent the former from escaping to the bulk.

Patients' views on the use of an Option Grid for knee osteoarthritis in physiotherapy clinical encounters: An interview study.

PubMed

Kinsey, Katharine; Firth, Jill; Elwyn, Glyn; Edwards, Adrian; Brain, Katherine; Marrin, Katy; Nye, Alan; Wood, Fiona

2017-12-01

Patient decision support tools have been developed as a means of providing accurate and accessible information in order for patients to make informed decisions about their care. Option Grids ™ are a type of decision support tool specifically designed to be used during clinical encounters. To explore patients' views of the Option Grid encounter tool used in clinical consultations with physiotherapists, in comparison with usual care, within a patient population who are likely to be disadvantaged by age and low health literacy. Semi-structured interviews with 72 patients (36 who had been given an Option Grid in their consultation and 36 who had not). Thematic analysis explored patients' understanding of treatment options, perceptions of involvement, and readability and utility of the Option Grid. Interviews suggested that the Option Grid facilitated more detailed discussion about the risks and benefits of a wider range of treatment options for osteoarthritis of the knee. Participants indicated that the Option Grid was clear and aided their understanding of a structured progression of the options as their condition advanced, although it was not clear whether the Option Grid facilitated greater engagement in shared decision making. The Option Grid for osteoarthritis of the knee was well received by patient participants who reported that it helped them to understand their options, and made the notion of choice explicit. Use of Option Grids should be considered within routine consultations. © 2017 The Authors Health Expectations Published by John Wiley & Sons Ltd.

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

CHARMM-GUI 10 Years for Biomolecular Modeling and Simulation

PubMed Central

Jo, Sunhwan; Cheng, Xi; Lee, Jumin; Kim, Seonghoon; Park, Sang-Jun; Patel, Dhilon S.; Beaven, Andrew H.; Lee, Kyu Il; Rui, Huan; Roux, Benoît; MacKerell, Alexander D.; Klauda, Jeffrey B.; Qi, Yifei

2017-01-01

CHARMM-GUI, http://www.charmm-gui.org, is a web-based graphical user interface that prepares complex biomolecular systems for molecular simulations. CHARMM-GUI creates input files for a number of programs including CHARMM, NAMD, GROMACS, AMBER, GENESIS, LAMMPS, Desmond, OpenMM, and CHARMM/OpenMM. Since its original development in 2006, CHARMM-GUI has been widely adopted for various purposes and now contains a number of different modules designed to set up a broad range of simulations: (1) PDB Reader & Manipulator, Glycan Reader, and Ligand Reader & Modeler for reading and modifying molecules; (2) Quick MD Simulator, Membrane Builder, Nanodisc Builder, HMMM Builder, Monolayer Builder, Micelle Builder, and Hex Phase Builder for building all-atom simulation systems in various environments; (3) PACE CG Builder and Martini Maker for building coarse-grained simulation systems; (4) DEER Facilitator and MDFF/xMDFF Utilizer for experimentally guided simulations; (5) Implicit Solvent Modeler, PBEQ-Solver, and GCMC/BD Ion Simulator for implicit solvent related calculations; (6) Ligand Binder for ligand solvation and binding free energy simulations; and (7) Drude Prepper for preparation of simulations with the CHARMM Drude polarizable force field. Recently, new modules have been integrated into CHARMM-GUI, such as Glycolipid Modeler for generation of various glycolipid structures, and LPS Modeler for generation of lipopolysaccharide structures from various Gram-negative bacteria. These new features together with existing modules are expected to facilitate advanced molecular modeling and simulation thereby leading to an improved understanding of the molecular details of the structure and dynamics of complex biomolecular systems. Here, we briefly review these capabilities and discuss potential future directions in the CHARMM-GUI development project. PMID:27862047

New systematic methodology for incorporating dynamic heat transfer modelling in multi-phase biochemical reactors.

PubMed

Fernández-Arévalo, T; Lizarralde, I; Grau, P; Ayesa, E

2014-09-01

This paper presents a new modelling methodology for dynamically predicting the heat produced or consumed in the transformations of any biological reactor using Hess's law. Starting from a complete description of model components stoichiometry and formation enthalpies, the proposed modelling methodology has integrated successfully the simultaneous calculation of both the conventional mass balances and the enthalpy change of reaction in an expandable multi-phase matrix structure, which facilitates a detailed prediction of the main heat fluxes in the biochemical reactors. The methodology has been implemented in a plant-wide modelling methodology in order to facilitate the dynamic description of mass and heat throughout the plant. After validation with literature data, as illustrative examples of the capability of the methodology, two case studies have been described. In the first one, a predenitrification-nitrification dynamic process has been analysed, with the aim of demonstrating the easy integration of the methodology in any system. In the second case study, the simulation of a thermal model for an ATAD has shown the potential of the proposed methodology for analysing the effect of ventilation and influent characterization. Copyright © 2014 Elsevier Ltd. All rights reserved.

Passive water collection with the integument: mechanisms and their biomimetic potential.

PubMed

Comanns, Philipp

2018-05-22

Several mechanisms of water acquisition have evolved in animals living in arid habitats to cope with limited water supply. They enable access to water sources such as rain, dew, thermally facilitated condensation on the skin, fog, or moisture from a damp substrate. This Review describes how a significant number of animals - in excess of 39 species from 24 genera - have acquired the ability to passively collect water with their integument. This ability results from chemical and structural properties of the integument, which, in each species, facilitate one or more of six basic mechanisms: increased surface wettability, increased spreading area, transport of water over relatively large distances, accumulation and storage of collected water, condensation, and utilization of gravity. Details are described for each basic mechanism. The potential for bio-inspired improvement of technical applications has been demonstrated in many cases, in particular for several wetting phenomena, fog collection and passive, directional transport of liquids. Also considered here are potential applications in the fields of water supply, lubrication, heat exchangers, microfluidics and hygiene products. These present opportunities for innovations, not only in product functionality, but also for fabrication processes, where resources and environmental impact can be reduced. © 2018. Published by The Company of Biologists Ltd.

Nanocomposites of AgInZnS and graphene nanosheets as efficient photocatalysts for hydrogen evolution

NASA Astrophysics Data System (ADS)

Tang, Xiaosheng; Chen, Weiwei; Zu, Zhiqiang; Zang, Zhigang; Deng, Ming; Zhu, Tao; Sun, Kuan; Sun, Lidong; Xue, Junmin

2015-11-01

In this study, AgInZnS-reduced graphene (AIZS-rGO) nanocomposites with tunable band gap absorption and large specific surface area were synthesized by a simple hydrothermal route, which showed highly efficient photocatalytic hydrogen evolution under visible-light irradiation. The relationships between their crystal structures, morphology, surface chemical states and photocatalytic activity have been explored in detail. Importantly, the AIZS-rGO nanocomposites with 0.02 wt% of graphene exhibited the highest hydrogen production rate of 1.871 mmol h-1 g-1, which was nearly 2 times the hydrogen production rate when using pure AIZS nanoparticles as the photocatalyst. This high photocatalytic H2-production activity was attributed predominantly to the incorporation of graphene sheets, which demonstrated an obvious influence on the structure and optical properties of the AIZS nanoparticles. In the AIZS-rGO nanocomposites, graphene could not only serve as an effective supporting layer but also is a recombination center for conduction band electrons and valence band holes. It is believed that this kind of graphene-based material would attract much attention as a promising photocatalyst with a high efficiency and a low cost for photocatalytic H2 evolution and facilitates their application in the environmental protection field.In this study, AgInZnS-reduced graphene (AIZS-rGO) nanocomposites with tunable band gap absorption and large specific surface area were synthesized by a simple hydrothermal route, which showed highly efficient photocatalytic hydrogen evolution under visible-light irradiation. The relationships between their crystal structures, morphology, surface chemical states and photocatalytic activity have been explored in detail. Importantly, the AIZS-rGO nanocomposites with 0.02 wt% of graphene exhibited the highest hydrogen production rate of 1.871 mmol h-1 g-1, which was nearly 2 times the hydrogen production rate when using pure AIZS nanoparticles as the photocatalyst. This high photocatalytic H2-production activity was attributed predominantly to the incorporation of graphene sheets, which demonstrated an obvious influence on the structure and optical properties of the AIZS nanoparticles. In the AIZS-rGO nanocomposites, graphene could not only serve as an effective supporting layer but also is a recombination center for conduction band electrons and valence band holes. It is believed that this kind of graphene-based material would attract much attention as a promising photocatalyst with a high efficiency and a low cost for photocatalytic H2 evolution and facilitates their application in the environmental protection field. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr05145b

The Lion King and the Hyaena Queen: large carnivore interactions and coexistence.

PubMed

Périquet, Stéphanie; Fritz, Hervé; Revilla, Eloy

2015-11-01

Interactions among species, which range from competition to facilitation, have profound effects on ecosystem functioning. Large carnivores are of particular importance in shaping community structure since they are at the top of the food chain, and many efforts are made to conserve such keystone species. Despite this, the mechanisms of carnivore interactions are far from understood, yet they are key to enabling or hindering their coexistence and hence are highly relevant for their conservation. The goal of this review is thus to provide detailed information on the extents of competition and facilitation between large carnivores and their impact in shaping their life histories. Here, we use the example of spotted hyaenas (Crocuta crocuta) and lions (Panthera leo) and provide a comprehensive knowledge of their interactions based on meta-analyses from available literature (148 publications). Despite their strong potential for both exploitation and interference competition (range and diet overlap, intraguild predation and kleptoparasitism), we underline some mechanisms facilitating their coexistence (different prey-age selection and scavenging opportunities). We stress the fact that prey abundance is key to their coexistence and that hyaenas forming very large groups in rich ecosystems could have a negative impact on lions. We show that the coexistence of spotted hyaenas and lions is a complex balance between competition and facilitation, and that prey availability within the ecosystem determines which predator is dominant. However, there are still many gaps in our knowledge such as the spatio-temporal dynamics of their interactions. As both species' survival becomes increasingly dependent on protected areas, where their densities can be high, it is critical to understand their interactions to inform both reintroduction programs and protected area management. © 2014 Cambridge Philosophical Society.

Facilitating higher-fidelity simulations of axial compressor instability and other turbomachinery flow conditions

NASA Astrophysics Data System (ADS)

Herrick, Gregory Paul

The quest to accurately capture flow phenomena with length-scales both short and long and to accurately represent complex flow phenomena within disparately sized geometry inspires a need for an efficient, high-fidelity, multi-block structured computational fluid dynamics (CFD) parallel computational scheme. This research presents and demonstrates a more efficient computational method by which to perform multi-block structured CFD parallel computational simulations, thus facilitating higher-fidelity solutions of complicated geometries (due to the inclusion of grids for "small'' flow areas which are often merely modeled) and their associated flows. This computational framework offers greater flexibility and user-control in allocating the resource balance between process count and wall-clock computation time. The principal modifications implemented in this revision consist of a "multiple grid block per processing core'' software infrastructure and an analytic computation of viscous flux Jacobians. The development of this scheme is largely motivated by the desire to simulate axial compressor stall inception with more complete gridding of the flow passages (including rotor tip clearance regions) than has been previously done while maintaining high computational efficiency (i.e., minimal consumption of computational resources), and thus this paradigm shall be demonstrated with an examination of instability in a transonic axial compressor. However, the paradigm presented herein facilitates CFD simulation of myriad previously impractical geometries and flows and is not limited to detailed analyses of axial compressor flows. While the simulations presented herein were technically possible under the previous structure of the subject software, they were much less computationally efficient and thus not pragmatically feasible; the previous research using this software to perform three-dimensional, full-annulus, time-accurate, unsteady, full-stage (with sliding-interface) simulations of rotating stall inception in axial compressors utilized tip clearance periodic models, while the scheme here is demonstrated by a simulation of axial compressor stall inception utilizing gridded rotor tip clearance regions. As will be discussed, much previous research---experimental, theoretical, and computational---has suggested that understanding clearance flow behavior is critical to understanding stall inception, and previous computational research efforts which have used tip clearance models have begged the question, "What about the clearance flows?''. This research begins to address that question.

Facilitating Facilitators: Enhancing PBL through a Structured Facilitator Development Program

ERIC Educational Resources Information Center

Salinitri, Francine D.; Wilhelm, Sheila M.; Crabtree, Brian L.

2015-01-01

With increasing adoption of the problem-based learning (PBL) model, creative approaches to enhancing facilitator training and optimizing resources to maintain effective learning in small groups is essential. We describe a theoretical framework for the development of a PBL facilitator training program that uses the constructivist approach as the…

Uncertainty quantification and validation of 3D lattice scaffolds for computer-aided biomedical applications.

PubMed

Gorguluarslan, Recep M; Choi, Seung-Kyum; Saldana, Christopher J

2017-07-01

A methodology is proposed for uncertainty quantification and validation to accurately predict the mechanical response of lattice structures used in the design of scaffolds. Effective structural properties of the scaffolds are characterized using a developed multi-level stochastic upscaling process that propagates the quantified uncertainties at strut level to the lattice structure level. To obtain realistic simulation models for the stochastic upscaling process and minimize the experimental cost, high-resolution finite element models of individual struts were reconstructed from the micro-CT scan images of lattice structures which are fabricated by selective laser melting. The upscaling method facilitates the process of determining homogenized strut properties to reduce the computational cost of the detailed simulation model for the scaffold. Bayesian Information Criterion is utilized to quantify the uncertainties with parametric distributions based on the statistical data obtained from the reconstructed strut models. A systematic validation approach that can minimize the experimental cost is also developed to assess the predictive capability of the stochastic upscaling method used at the strut level and lattice structure level. In comparison with physical compression test results, the proposed methodology of linking the uncertainty quantification with the multi-level stochastic upscaling method enabled an accurate prediction of the elastic behavior of the lattice structure with minimal experimental cost by accounting for the uncertainties induced by the additive manufacturing process. Copyright © 2017 Elsevier Ltd. All rights reserved.

Short-term adaptation and chronic cardiac remodelling to high altitude in lowlander natives and Himalayan Sherpa.

PubMed

Stembridge, Mike; Ainslie, Philip N; Shave, Rob

2015-11-01

What is the topic of this review? At high altitude, the cardiovascular system must adapt in order to meet the metabolic demand for oxygen. This review summarizes recent findings relating to short-term and life-long cardiac adaptation to high altitude in the context of exercise capacity. What advances does it highlight? Both Sherpa and lowlanders exhibit smaller left ventricular volumes at high altitude; however, myocardial relaxation, as evidenced by diastolic untwist, is reduced only in Sherpa, indicating that short-term hypoxia does not impair diastolic relaxation. Potential remodelling of systolic function, as evidenced by lower left ventricular systolic twist in Sherpa, may facilitate the requisite sea-level mechanical reserve required during exercise, although this remains to be confirmed. Both short-term and life-long high-altitude exposure challenge the cardiovascular system to meet the metabolic demand for O2 in a hypoxic environment. As the demand for O2 delivery increases during exercise, the circulatory component of oxygen transport is placed under additional stress. Acute adaptation and chronic remodelling of cardiac structure and function may occur to facilitate O2 delivery in lowlanders during sojourn to high altitude and in permanent highland residents. However, our understanding of cardiac structural and functional adaption in Sherpa remains confined to a higher maximal heart rate, lower pulmonary vascular resistance and no differences in resting cardiac output. Ventricular form and function are intrinsically linked through the left ventricular (LV) mechanics that facilitate efficient ejection, minimize myofibre stress during contraction and aid diastolic recoil. Recent examination of LV mechanics has allowed detailed insight into fundamental cardiac adaptation in high-altitude Sherpa. In this symposium report, we review recent advances in our understanding of LV function in both lowlanders and Sherpa at rest and discuss the potential consequences for exercise capacity. Collectively, data indicate chronic structural ventricular adaptation, with adult Sherpa having smaller absolute and relative LV size. Consistent with structural remodelling, cardiac mechanics also differ in Sherpa when compared with lowlanders at high altitude. These differences are characterized by a reduction in resting systolic deformation and slower diastolic untwisting, a surrogate of relaxation. These changes may reflect a functional cardiac adaptation that affords Sherpa the same mechanical reserve seen in lowlanders at sea level, which is absent when they ascend to high altitude. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

“Going Episodic”: Collaborative Inhibition and Facilitation When Long-Married Couples Remember Together

PubMed Central

Harris, Celia B.; Barnier, Amanda J.; Sutton, John; Keil, Paul G.; Dixon, Roger A.

2017-01-01

Two complementary approaches to the study of collaborative remembering have produced contrasting results. In the experimental “collaborative recall” approach within cognitive psychology, collaborative remembering typically results in ‘collaborative inhibition’: laboratory groups recall fewer items than their estimated potential. In the cognitive ageing approach, collaborative remembering with a partner or spouse may provide cuing and support to benefit older adults’ performance on everyday memory tasks. To combine the value of experimental and cognitive ageing approaches, we tested the effects of collaborative remembering in older, long-married couples who recalled a non-personal word list and a personal semantic list of shared trips. We scored amount recalled as well as the kinds of details remembered. We found evidence for collaborative inhibition across both tasks when scored strictly as number of list items recalled. However, we found collaborative facilitation of specific episodic details on the personal semantic list, details which were not strictly required for the completion of the task. In fact, there was a trade-off between recall of specific episodic details and number of trips recalled during collaboration. We discuss these results in terms of the functions of shared remembering and what constitutes memory success, particularly for intimate groups and for older adults. PMID:28071300

Lipopeptide biosurfactant viscosin enhances dispersal of Pseudomonas fluorescens SBW25 biofilms

PubMed Central

Bygvraa Svenningsen, Nanna; Rybtke, Morten; de Bruijn, Irene; Raaijmakers, Jos M.; Tolker-Nielsen, Tim; Nybroe, Ole

2015-01-01

Pseudomonads produce several lipopeptide biosurfactants that have antimicrobial properties but that also facilitate surface motility and influence biofilm formation. Detailed studies addressing the significance of lipopeptides for biofilm formation and architecture are rare. Hence, the present study sets out to determine the specific role of the lipopeptide viscosin in Pseudomonas fluorescens SBW25 biofilm formation, architecture and dispersal, and to relate viscA gene expression to viscosin production and effect. Initially, we compared biofilm formation of SBW25 and the viscosin-deficient mutant strain SBW25ΔviscA in static microtitre assays. These experiments demonstrated that viscosin had little influence on the amount of biofilm formed by SBW25 during the early stages of biofilm development. Later, however, SBW25 formed significantly less biofilm than SBW25ΔviscA. The indication that viscosin is involved in biofilm dispersal was confirmed by chemical complementation of the mutant biofilm. Furthermore, a fluorescent bioreporter showed that viscA expression was induced in biofilms 4 h prior to dispersal. Subsequent detailed studies of biofilms formed in flow cells for up to 5 days revealed that SBW25 and SBW25ΔviscA developed comparable biofilms dominated by well-defined, mushroom-shaped structures. Carbon starvation was required to obtain biofilm dispersal in this system. Dispersal of SBW25 biofilms was significantly greater than of SBW25ΔviscA biofilms after 3 h and, importantly, carbon starvation strongly induced viscA expression, in particular for cells that were apparently leaving the biofilm. Thus, the present study points to a role for viscosin-facilitated motility in dispersal of SBW25 biofilms. PMID:26419730

ClinicalTrials.gov as a data source for semi-automated point-of-care trial eligibility screening.

PubMed

Pfiffner, Pascal B; Oh, JiWon; Miller, Timothy A; Mandl, Kenneth D

2014-01-01

Implementing semi-automated processes to efficiently match patients to clinical trials at the point of care requires both detailed patient data and authoritative information about open studies. To evaluate the utility of the ClinicalTrials.gov registry as a data source for semi-automated trial eligibility screening. Eligibility criteria and metadata for 437 trials open for recruitment in four different clinical domains were identified in ClinicalTrials.gov. Trials were evaluated for up to date recruitment status and eligibility criteria were evaluated for obstacles to automated interpretation. Finally, phone or email outreach to coordinators at a subset of the trials was made to assess the accuracy of contact details and recruitment status. 24% (104 of 437) of trials declaring on open recruitment status list a study completion date in the past, indicating out of date records. Substantial barriers to automated eligibility interpretation in free form text are present in 81% to up to 94% of all trials. We were unable to contact coordinators at 31% (45 of 146) of the trials in the subset, either by phone or by email. Only 53% (74 of 146) would confirm that they were still recruiting patients. Because ClinicalTrials.gov has entries on most US and many international trials, the registry could be repurposed as a comprehensive trial matching data source. Semi-automated point of care recruitment would be facilitated by matching the registry's eligibility criteria against clinical data from electronic health records. But the current entries fall short. Ultimately, improved techniques in natural language processing will facilitate semi-automated complex matching. As immediate next steps, we recommend augmenting ClinicalTrials.gov data entry forms to capture key eligibility criteria in a simple, structured format.

Lipopeptide biosurfactant viscosin enhances dispersal of Pseudomonas fluorescens SBW25 biofilms.

PubMed

Bonnichsen, Lise; Bygvraa Svenningsen, Nanna; Rybtke, Morten; de Bruijn, Irene; Raaijmakers, Jos M; Tolker-Nielsen, Tim; Nybroe, Ole

2015-12-01

Pseudomonads produce several lipopeptide biosurfactants that have antimicrobial properties but that also facilitate surface motility and influence biofilm formation. Detailed studies addressing the significance of lipopeptides for biofilm formation and architecture are rare. Hence, the present study sets out to determine the specific role of the lipopeptide viscosin in Pseudomonas fluorescens SBW25 biofilm formation, architecture and dispersal, and to relate viscA gene expression to viscosin production and effect. Initially, we compared biofilm formation of SBW25 and the viscosin-deficient mutant strain SBW25ΔviscA in static microtitre assays. These experiments demonstrated that viscosin had little influence on the amount of biofilm formed by SBW25 during the early stages of biofilm development. Later, however, SBW25 formed significantly less biofilm than SBW25ΔviscA. The indication that viscosin is involved in biofilm dispersal was confirmed by chemical complementation of the mutant biofilm. Furthermore, a fluorescent bioreporter showed that viscA expression was induced in biofilms 4 h prior to dispersal. Subsequent detailed studies of biofilms formed in flow cells for up to 5 days revealed that SBW25 and SBW25ΔviscA developed comparable biofilms dominated by well-defined, mushroom-shaped structures. Carbon starvation was required to obtain biofilm dispersal in this system. Dispersal of SBW25 biofilms was significantly greater than of SBW25ΔviscA biofilms after 3 h and, importantly, carbon starvation strongly induced viscA expression, in particular for cells that were apparently leaving the biofilm. Thus, the present study points to a role for viscosin-facilitated motility in dispersal of SBW25 biofilms.

Friedreich's Ataxia Variants I154F and W155R Diminish Frataxin-Based Activation of the Iron-Sulfur Cluster Assembly Complex

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

Tsai, Chi-Lin; Bridwell-Rabb, Jennifer; Barondeau, David P

2011-11-07

Friedreich's ataxia (FRDA) is a progressive neurodegenerative disease that has been linked to defects in the protein frataxin (Fxn). Most FRDA patients have a GAA expansion in the first intron of their Fxn gene that decreases protein expression. Some FRDA patients have a GAA expansion on one allele and a missense mutation on the other allele. Few functional details are known for the ~15 different missense mutations identified in FRDA patients. Here in vitro evidence is presented that indicates the FRDA I154F and W155R variants bind more weakly to the complex of Nfs1, Isd11, and Isu2 and thereby are defectivemore » in forming the four-component SDUF complex that constitutes the core of the Fe-S cluster assembly machine. The binding affinities follow the trend Fxn ~ I154F > W155F > W155A ~ W155R. The Fxn variants also have diminished ability to function as part of the SDUF complex to stimulate the cysteine desulfurase reaction and facilitate Fe-S cluster assembly. Four crystal structures, including the first for a FRDA variant, reveal specific rearrangements associated with the loss of function and lead to a model for Fxn-based activation of the Fe-S cluster assembly complex. Importantly, the weaker binding and lower activity for FRDA variants correlate with the severity of disease progression. Together, these results suggest that Fxn facilitates sulfur transfer from Nfs1 to Isu2 and that these in vitro assays are sensitive and appropriate for deciphering functional defects and mechanistic details for human Fe-S cluster biosynthesis.« less

An interactive graphics system to facilitate finite element structural analysis

NASA Technical Reports Server (NTRS)

Burk, R. C.; Held, F. H.

1973-01-01

The characteristics of an interactive graphics systems to facilitate the finite element method of structural analysis are described. The finite element model analysis consists of three phases: (1) preprocessing (model generation), (2) problem solution, and (3) postprocessing (interpretation of results). The advantages of interactive graphics to finite element structural analysis are defined.

Constructal Law of Vascular Trees for Facilitation of Flow

PubMed Central

Razavi, Mohammad S.; Shirani, Ebrahim; Salimpour, Mohammad Reza; Kassab, Ghassan S.

2014-01-01

Diverse tree structures such as blood vessels, branches of a tree and river basins exist in nature. The constructal law states that the evolution of flow structures in nature has a tendency to facilitate flow. This study suggests a theoretical basis for evaluation of flow facilitation within vascular structure from the perspective of evolution. A novel evolution parameter (Ev) is proposed to quantify the flow capacity of vascular structures. Ev is defined as the ratio of the flow conductance of an evolving structure (configuration with imperfection) to the flow conductance of structure with least imperfection. Attaining higher Ev enables the structure to expedite flow circulation with less energy dissipation. For both Newtonian and non-Newtonian fluids, the evolution parameter was developed as a function of geometrical shape factors in laminar and turbulent fully developed flows. It was found that the non-Newtonian or Newtonian behavior of fluid as well as flow behavior such as laminar or turbulent behavior affects the evolution parameter. Using measured vascular morphometric data of various organs and species, the evolution parameter was calculated. The evolution parameter of the tree structures in biological systems was found to be in the range of 0.95 to 1. The conclusion is that various organs in various species have high capacity to facilitate flow within their respective vascular structures. PMID:25551617

Study on Detailing Design of Precast Concrete Frame Structure

NASA Astrophysics Data System (ADS)

Lida, Tian; Liming, Li; Kang, Liu; Jiao, Geng; Ming, Li

2018-03-01

Taking a certain precast concrete frame structure as an example, this paper introduces the general procedures and key points in detailing design of emulative cast-in-place prefabricated structure from the aspects of structural scheme, precast element layout, shop drawing design and BIM 3D modelling. This paper gives a practical solution for the detailing design of precast concrete frame structure under structural design codes in China.

Comparative Aspects of Osteosarcoma Pathogenesis in Humans and Dogs

PubMed Central

Fan, Timothy M.; Khanna, Chand

2015-01-01

Osteosarcoma (OS) is a primary and aggressive bone sarcoma affecting the skeleton of two principal species, human beings and canines. The biologic behavior of OS is conserved between people and dogs, and evidence suggests that fundamental discoveries in OS biology can be facilitated through detailed and comparative studies. In particular, the relative genetic homogeneity associated with specific dog breeds can provide opportunities to facilitate the discovery of key genetic drivers involved in OS pathogenesis, which, to-date, remain elusive. In this review, known causative factors that predispose to the development OS in human beings and dogs are summarized in detail. Based upon the commonalities shared in OS pathogenesis, it is likely that foundational discoveries in one species will be translationally relevant to the other and emphasizes the unique opportunities that might be gained through comparative scientific approaches. PMID:29061942

Operational Details of the Five Domains Model and Its Key Applications to the Assessment and Management of Animal Welfare

PubMed Central

Mellor, David J.

2017-01-01

Simple Summary The Five Domains Model is a focusing device to facilitate systematic, structured, comprehensive and coherent assessment of animal welfare; it is not a definition of animal welfare, nor is it intended to be an accurate representation of body structure and function. The purpose of each of the five domains is to draw attention to areas that are relevant to both animal welfare assessment and management. This paper begins by briefly describing the major features of the Model and the operational interactions between the five domains, and then it details seven interacting applications of the Model. These underlie its utility and increasing application to welfare assessment and management in diverse animal use sectors. Abstract In accord with contemporary animal welfare science understanding, the Five Domains Model has a significant focus on subjective experiences, known as affects, which collectively contribute to an animal’s overall welfare state. Operationally, the focus of the Model is on the presence or absence of various internal physical/functional states and external circumstances that give rise to welfare-relevant negative and/or positive mental experiences, i.e., affects. The internal states and external circumstances of animals are evaluated systematically by referring to each of the first four domains of the Model, designated “Nutrition”, “Environment”, “Health” and “Behaviour”. Then affects, considered carefully and cautiously to be generated by factors in these domains, are accumulated into the fifth domain, designated “Mental State”. The scientific foundations of this operational procedure, published in detail elsewhere, are described briefly here, and then seven key ways the Model may be applied to the assessment and management of animal welfare are considered. These applications have the following beneficial objectives—they (1) specify key general foci for animal welfare management; (2) highlight the foundations of specific welfare management objectives; (3) identify previously unrecognised features of poor and good welfare; (4) enable monitoring of responses to specific welfare-focused remedial interventions and/or maintenance activities; (5) facilitate qualitative grading of particular features of welfare compromise and/or enhancement; (6) enable both prospective and retrospective animal welfare assessments to be conducted; and, (7) provide adjunct information to support consideration of quality of life evaluations in the context of end-of-life decisions. However, also noted is the importance of not overstating what utilisation of the Model can achieve. PMID:28792485

Clinical expectations: what facilitators expect from ESL students on clinical placement.

PubMed

San Miguel, Caroline; Rogan, Fran

2012-03-01

Many nursing students for whom English is a second language (ESL) face challenges related to communication on clinical placement and although clinical facilitators are not usually trained language assessors, they are often in a position of needing to assess ESL students' clinical language performance. Little is known, however, about the particular areas of clinical performance facilitators focus on when they are assessing ESL students. This paper discusses the results of a study of facilitators' written assessment comments about the clinical performance of a small group of ESL nursing students over a two and a half year period. These comments were documented on students' clinical assessment forms at the end of each placement. The results provide a more detailed insight into facilitators' expectations of students' language performance and the particular challenges faced by ESL students and indicate that facilitators have clear expectations of ESL students regarding communication, learning styles and professional demeanour. These findings may help both ESL students and their facilitators better prepare for clinical placement. Copyright © 2011 Elsevier Ltd. All rights reserved.

Assessing the effectiveness of the NICHD investigative interview protocol when interviewing French-speaking alleged victims of child sexual abuse in Quebec.

PubMed

Cyr, Mireille; Lamb, Michael E

2009-05-01

The study was designed to assess the effectiveness of the flexibly structured NICHD Investigative Interview Protocol for child sexual abuse (CSA) investigative interviews by police officers and mental health workers in Quebec. The NICHD Protocol was designed to operationalize "best practice" guidelines and to help forensic interviewers use open-ended prompts to facilitate free recall by alleged victims. A total of 83 interviews with 3- to 13-year-old alleged victims were matched with 83 interviews conducted by the same interviewers before they were trained to use the Protocol. Interviews were matched with respect to the children's ages, children-perpetrator relationships, and the types and frequency of abuse. Coders categorized each of the prompts used to elicit information about the abuse and tabulated the numbers of new forensically relevant details provided in each response. Interviewers used three times as many open-ended prompts in Protocol interviews than in non-Protocol interviews, whereas use of all other types of questions was halved, and the total number of questions asked decreased by 25%. Protocol-guided interviews yielded more details than comparison interviews. The mean number of details per prompt increased from 3 to 5 details when the Protocol was used. Even with young children, interviewers using the Protocol employed more invitations to elicit forensically relevant details. French-speaking investigators using the NICHD Protocol used open-ended prompts rather than focused questions when interviewing alleged victims. In addition, these interviewers needed fewer questions to get relevant information when using the Protocol. A French version of the NICHD Protocol is now available to police officers and social workers who investigate the alleged sexual abuse of young children in French-speaking countries. This French version allowed trained interviewers to increase the use of invitations and reduce the use of more focused and risky questions. When the number of questions was controlled, more central details and more details in total were obtained in Protocol interviews, because the average prompt elicited more detailed answers in Protocol interviews. However, learning to use the NICHD Protocol required extended training and continued feedback sessions to maintain the high quality of interviewing.

3D high-resolution radar imaging of small body interiors

NASA Astrophysics Data System (ADS)

Sava, Paul; Asphaug, Erik

2017-10-01

Answering fundamental questions about the origin and evolution of small planetary bodies hinges on our ability to image their interior structure in detail and at high resolution (Asphaug, 2009). We often infer internal structure from surface observations, e.g. that comet 67P/Churyumov-Gerasimenko is a primordial agglomeration of cometesimals (Massironi et al., 2015). However, the interior structure is not easily accessible without systematic imaging using, e.g., radar transmission and reflection data, as suggested by the CONSERT experiment on Rosetta. Interior imaging depends on observations from multiple viewpoints, as in medical tomography.We discuss radar imaging using methodology adapted from terrestrial exploration seismology (Sava et al., 2015). We primarily focus on full wavefield methods that facilitate high quality imaging of small body interiors characterized by complex structure and large contrasts of physical properties. We consider the case of a monostatic system (co-located transmitters and receivers) operated at two frequency bands, centered around 5 and 15 MHz, from a spacecraft in slow polar orbit around a spinning comet nucleus. Assuming that the spin period is significantly (e.g. 5x) faster than the orbital period, this configuration allows repeated views from multiple directions (Safaeinili et al., 2002)Using realistic numerical experiments, we argue that (1) the comet/asteroid imaging problem is intrinsically 3D and conventional SAR methodology does not satisfy imaging, sampling and resolution requirements; (2) imaging at different frequency bands can provide information about internal surfaces (through migration) and internal volumes (through tomography); (3) interior imaging can be accomplished progressively as data are being acquired through successive orbits around the studied object; (4) imaging resolution can go beyond the apparent radar frequency band by deconvolution of the point-spread-function characterizing the imaging system; and (5) exploiting the known (and complex) exterior shape of the studied body facilitates high-resolution imaging and tomography comparable with what could be accomplished by bi/multi-static systems.

Effect of direct reciprocity and network structure on continuing prosperity of social networking services.

PubMed

Osaka, Kengo; Toriumi, Fujio; Sugawara, Toshihauru

2017-01-01

Social networking services (SNSs) are widely used as communicative tools for a variety of purposes. SNSs rely on the users' individual activities associated with some cost and effort, and thus it is not known why users voluntarily continue to participate in SNSs. Because the structures of SNSs are similar to that of the public goods (PG) game, some studies have focused on why voluntary activities emerge as an optimal strategy by modifying the PG game. However, their models do not include direct reciprocity between users, even though reciprocity is a key mechanism that evolves and sustains cooperation in human society. We developed an abstract SNS model called the reciprocity rewards and meta-rewards games that include direct reciprocity by extending the existing models. Then, we investigated how direct reciprocity in an SNS facilitates cooperation that corresponds to participation in SNS by posting articles and comments and how the structure of the networks of users exerts an influence on the strategies of users using the reciprocity rewards game. We run reciprocity rewards games on various complex networks and an instance network of Facebook and found that two types of stable cooperation emerged. First, reciprocity slightly improves the rate of cooperation in complete graphs but the improvement is insignificant because of the instability of cooperation. However, this instability can be avoided by making two assumptions: high degree of fun, i.e. articles are read with high probability, and different attitudes to reciprocal and non-reciprocal agents. We then propose the concept of half free riders to explain what strategy sustains cooperation-dominant situations. Second, we indicate that a certain WS network structure affects users' optimal strategy and facilitates stable cooperation without any extra assumptions. We give a detailed analysis of the different characteristics of the two types of cooperation-dominant situations and the effect of the memory of reciprocal agents on cooperation.

[SCAN system--semi-structured interview based on diagnostic criteria].

PubMed

Adamowski, Tomasz; Kiejna, Andrzej; Hadryś, Tomasz

2006-01-01

This paper presents the main features of contemporary diagnostic systems which are implemented into the SCAN--modern and semi-structured diagnostic interview. The concepts of further development of the classifications, rationale for operationalized diagnostic criteria and for the divisional approach to mental diagnoses will be in focus. The structure and components of SCAN ver. 2.1 (WHO), i.e. Present State Examination--10th edition, Item Group Checklist, Clinical History Schedule, Glossary of Definitions and computer software with the diagnostic algorithm: I-Shell, as well as rules for a reliable use of diagnostic rating scales, will be discussed within the scope of this paper. The materials and training sets necessary for the learning of proper use of the SCAN, especially training sets for SCAN Training Centers and the Reference Manual--a form of guidebook for SCAN shall be introduced. Finally the paper will present evidence that SCAN is an instrument feasible in different cultural settings. Reliability and validity data of SCAN will also be dealt with indicating that SCAN could be widely used in research studies as well as in everyday clinical practice facilitating more detailed diagnostic approach to a patient.

Diversity of basaltic lunar volcanism associated with buried impact structures: Implications for intrusive and extrusive events

NASA Astrophysics Data System (ADS)

Zhang, F.; Zhu, M.-H.; Bugiolacchi, R.; Huang, Q.; Osinski, G. R.; Xiao, L.; Zou, Y. L.

2018-06-01

Relatively denser basalt infilling and the upward displacement of the crust-mantle interface are thought to be contributing factors for the quasi-circular mass anomalies for buried impact craters in the lunar maria. Imagery and gravity observations from the Lunar Reconnaissance Orbiter (LRO) and dual Gravity Recovery and Interior Laboratory (GRAIL) missions have identified 10 partially or fully buried impact structures where diversity of observable basaltic mare volcanism exists. With a detailed investigation of the characteristics of associated volcanic landforms, we describe their spatial distribution relationship with respect to the subsurface tectonic structure of complex impact craters and propose possible models for the igneous processes which may take advantage of crater-related zones of weakness and enable magmas to reach the surface. We conclude that the lunar crust, having been fractured and reworked extensively by cratering, facilitates substance and energy exchange between different lunar systems, an effect modulated by tectonic activities both at global and regional scales. In addition, we propose that the intrusion-caused contribution to gravity anomalies should be considered in future studies, although this is commonly obscured by other physical factors such as mantle uplift and basalt load.

Structural approaches to knowledge exchange: comparing practices across five centres of excellence in public health.

PubMed

Van der Graaf, P; Francis, O; Doe, E; Barrett, E; O'Rorke, M; Docherty, G

2018-03-01

In 2008, five UKCRC Public Health Research Centres of Excellence were created to develop a coordinated approach to policy and practice engagement and knowledge exchange. The five Centres have developed their own models and practices for achieving these aims, which have not been compared in detail to date. We applied an extended version of Saner's model for the interface between science and policy to compare five case studies of knowledge exchanges, one from each centre. We compared these practices on three dimensions within our model (focus, function and type/scale) to identify barriers and facilitators for knowledge exchange. The case studies shared commonalities in their range of activities (type) but illustrated different ways of linking these activities (function). The Centres' approaches ranged from structural to more organic, and varied in the extent that they engaged internal audiences (focus). Each centre addressed policymakers at different geographical levels and scale. This article emphasizes the importance of linking a range of activities that engage policymakers at different levels, intensities and points in their decision-making processes to build relationships. Developing a structural approach to knowledge exchange activities in different contexts presents challenges of resource, implementation and evaluation.

High yield bacterial expression, purification and characterisation of bioactive Human Tousled-like Kinase 1B involved in cancer.

PubMed

Bhoir, Siddhant; Shaik, Althaf; Thiruvenkatam, Vijay; Kirubakaran, Sivapriya

2018-03-19

Human Tousled-like kinases (TLKs) are highly conserved serine/threonine protein kinases responsible for cell proliferation, DNA repair, and genome surveillance. Their possible involvement in cancer via efficient DNA repair mechanisms have made them clinically relevant molecular targets for anticancer therapy. Innovative approaches in chemical biology have played a key role in validating the importance of kinases as molecular targets. However, the detailed understanding of the protein structure and the mechanisms of protein-drug interaction through biochemical and biophysical techniques demands a method for the production of an active protein of exceptional stability and purity on a large scale. We have designed a bacterial expression system to express and purify biologically active, wild-type Human Tousled-like Kinase 1B (hTLK1B) by co-expression with the protein phosphatase from bacteriophage λ. We have obtained remarkably high amounts of the soluble and homogeneously dephosphorylated form of biologically active hTLK1B with our unique, custom-built vector design strategy. The recombinant hTLK1B can be used for the structural studies and may further facilitate the development of new TLK inhibitors for anti-cancer therapy using a structure-based drug design approach.

Exploring the personality structure in the 11 languages of South Africa.

PubMed

Nel, Jan Alewyn; Valchev, Velichko H; Rothmann, Sebastiaan; van de Vijver, Fons J R; Meiring, Deon; de Bruin, Gideon P

2012-08-01

The present study, part of the development of the South African Personality Inventory (SAPI), explores the implicit personality structure in the 11 official language groups of South Africa by employing a mixed-method approach. In the first, qualitative part of the study, semistructured interviews were conducted with 1,216 participants from the 11 official language groups. The derived personality-descriptive terms were categorized and clustered based on their semantic relations in iterative steps involving group discussions and contacts with language and cultural experts. This analysis identified 37 subclusters, which could be merged in 9 broad clusters: Conscientiousness, Emotional Stability, Extraversion, Facilitating, Integrity, Intellect, Openness, Relationship Harmony, and Soft-Heartedness. In the second, quantitative part, the perceived relations between the 37 subclusters were rated by 204 students from different language groups in South Africa and 95 students in the Netherlands. The outcomes generally supported the adequacy of the conceptual model, although several clusters in the domain of relational and social functioning did not replicate in detail. The outcomes of these studies revealed a personality structure with a strong emphasis on social-relational aspects of personality. © 2011 The Authors. Journal of Personality © 2011, Wiley Periodicals, Inc.

A national facility for biological cryo-electron microscopy

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

Saibil, Helen R., E-mail: h.saibil@mail.cryst.bbk.ac.uk; Grünewald, Kay; Stuart, David I.

2015-01-01

This review provides a brief update on the use of cryo-electron microscopy for integrated structural biology, along with an overview of the plans for the UK national facility for electron microscopy being built at the Diamond synchrotron. Three-dimensional electron microscopy is an enormously powerful tool for structural biologists. It is now able to provide an understanding of the molecular machinery of cells, disease processes and the actions of pathogenic organisms from atomic detail through to the cellular context. However, cutting-edge research in this field requires very substantial resources for equipment, infrastructure and expertise. Here, a brief overview is provided ofmore » the plans for a UK national three-dimensional electron-microscopy facility for integrated structural biology to enable internationally leading research on the machinery of life. State-of-the-art equipment operated with expert support will be provided, optimized for both atomic-level single-particle analysis of purified macromolecules and complexes and for tomography of cell sections. The access to and organization of the facility will be modelled on the highly successful macromolecular crystallography (MX) synchrotron beamlines, and will be embedded at the Diamond Light Source, facilitating the development of user-friendly workflows providing near-real-time experimental feedback.« less

Detailed surface morphology of the 'lobster louse' copepod, Nicothoë astaci, a haematophagous gill parasite of the European lobster, Homarus gammarus.

PubMed

Davies, Charlotte E; Thomas, Gethin R; Maffeis, Thierry G G; Wootton, Emma C; Penny, Mark W; Rowley, Andrew F

2014-10-01

The ectoparasitic copepod, Nicothoë astaci (the 'lobster louse'), infests the gills of the European lobster, Homarus gammarus. There have been limited studies on this haematophagous species; therefore knowledge of this parasite is rudimentary. The current study examines the surface morphology of this parasitic copepod, detached from the host, concentrating on adaptations of the suctorial mouthpart, the oral disc. Cryo-scanning electron microscopy revealed structural adaptations that facilitate attachment of these parasites to the gill filaments of their lobster host. The aperture of the feeding channel, through which host haemolymph is drawn, is only ca. 5μm in diameter. The edge of the oral disc is lined with numerous setae, whilst the surface of the disc is covered with large numbers of small (<1μm in diameter) teeth-like structures, which presumably pierce through, and grip, the cuticle lining of the host's gill. Overall, these structures are thought to provide a 'vacuum seal' to assist in pumping of blood, via peristalsis, into the alimentary canal of the copepod host. Copyright © 2014 Elsevier Inc. All rights reserved.

Building Capacity in Understanding Foundational Biology Concepts: A K-12 Learning Progression in Genetics Informed by Research on Children's Thinking and Learning

NASA Astrophysics Data System (ADS)

Elmesky, Rowhea

2013-06-01

This article describes the substance, structure, and rationale of a learning progression in genetics spanning kindergarten through twelfth grade (K-12). The learning progression is designed to build a foundation towards understanding protein structure and activity and should be viewed as one possible pathway to understanding concepts of genetics and ultimately protein expression, based on the existing research. The kindergarten through fifth grade segment reflects findings that show children have a rich knowledge base and sophisticated cognitive abilities, and therefore, is designed so that elementary-aged children can learn content in deep and abstract manners, as well as apply scientific explanations appropriate to their knowledge level. The article also details the LP segment facilitating secondary students' understanding by outlining the overlapping conceptual frames which guide student learning from cell structures and functions to cell splitting (both cell division and gamete formation) to genetics as trait transmission, culminating in genetics as protein expression. The learning progression product avoids the use of technical language, which has been identified as a prominent source of student misconceptions in learning cellular biology, and explicit connections between cellular and macroscopic phenomena are encouraged.

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

Schmandt, Nicolaus; Velisetty, Phanindra; Chalamalasetti, Sreevatsa V.

Recent high resolution structures of several pentameric ligand–gated ion channels have provided unprecedented details of their molecular architecture. However, the conformational dynamics and structural rearrangements that underlie gating and allosteric modulation remain poorly understood. We used a combination of electrophysiology, double electron–electron resonance (DEER) spectroscopy, and x-ray crystallography to investigate activation mechanisms in a novel functional chimera with the extracellular domain (ECD) of amine-gated Erwinia chrysanthemi ligand–gated ion channel, which is activated by primary amines, and the transmembrane domain of Gloeobacter violaceus ligand–gated ion channel, which is activated by protons. We found that the chimera was independently gated by primarymore » amines and by protons. The crystal structure of the chimera in its resting state, at pH 7.0 and in the absence of primary amines, revealed a closed-pore conformation and an ECD that is twisted with respect to the transmembrane region. Amine- and pH-induced conformational changes measured by DEER spectroscopy showed that the chimera exhibits a dual mode of gating that preserves the distinct conformational changes of the parent channels. Collectively, our findings shed light on both conserved and divergent features of gating mechanisms in this class of channels, and will facilitate the design of better allosteric modulators.« less

Leadership capabilities of physiotherapy leaders in Ireland: Part 1 physiotherapy managers.

PubMed

McGowan, Emer; Elliott, Naomi; Stokes, Emma

2018-05-07

Investigation of the leadership capabilities of physiotherapists is needed to allow understanding of current leadership practice and to enable appropriate training programs to be developed. To explore physiotherapy managers´ perceptions of their leadership capabilities. Semi-structured interviews were conducted with a purposive sample of 18 physiotherapy managers from a range of public services and private practices in Ireland. The interviews were analyzed using template analysis and the coding template was based on the Bolman and Deal Leadership framework which details four leadership frames: structural, human resource, political, and symbolic. The physiotherapy managers described demonstrating leadership capabilities associated with each of the four leadership frames. However, the language used by the physiotherapy managers suggested that they work predominantly through the structural and human resource frames. The employment of capabilities associated with the political frame varied between participants; some participants described working through this frame while others reported difficulties. The symbolic frame was underused; there were fewer examples given of capabilities such as communicating their vision, demonstrating passion and facilitating a positive workplace culture. Physiotherapy managers work predominantly through the structural and human resource frames. To successfully meet the leadership requirements of their roles physiotherapy managers may benefit from specific leadership development training to develop leadership capabilities in the political and symbolic frames.

Structures of human folate receptors reveal biological trafficking states and diversity in folate and antifolate recognition.

PubMed

Wibowo, Ardian S; Singh, Mirage; Reeder, Kristen M; Carter, Joshua J; Kovach, Alexander R; Meng, Wuyi; Ratnam, Manohar; Zhang, Faming; Dann, Charles E

2013-09-17

Antifolates, folate analogs that inhibit vitamin B9 (folic acid)-using cellular enzymes, have been used over several decades for the treatment of cancer and inflammatory diseases. Cellular uptake of the antifolates in clinical use occurs primarily via widely expressed facilitative membrane transporters. More recently, human folate receptors (FRs), high affinity receptors that transport folate via endocytosis, have been proposed as targets for the specific delivery of new classes of antifolates or folate conjugates to tumors or sites of inflammation. The development of specific, FR-targeted antifolates would be accelerated if additional biophysical data, particularly structural models of the receptors, were available. Here we describe six distinct crystallographic models that provide insight into biological trafficking of FRs and distinct binding modes of folate and antifolates to these receptors. From comparison of the structures, we delineate discrete structural conformations representative of key stages in the endocytic trafficking of FRs and propose models for pH-dependent conformational changes. Additionally, we describe the molecular details of human FR in complex with three clinically prevalent antifolates, pemetrexed (also Alimta), aminopterin, and methotrexate. On the whole, our data form the basis for rapid design and implementation of unique, FR-targeted, folate-based drugs for the treatment of cancer and inflammatory diseases.

Fab Chaperone-Assisted RNA Crystallography (Fab CARC).

PubMed

Sherman, Eileen; Archer, Jennifer; Ye, Jing-Dong

2016-01-01

Recent discovery of structured RNAs such as ribozymes and riboswitches shows that there is still much to learn about the structure and function of RNAs. Knowledge learned can be employed in both biochemical research and clinical applications. X-ray crystallography gives unparalleled atomic-level structural detail from which functional inferences can be deduced. However, the difficulty in obtaining high-quality crystals and their phasing information make it a very challenging task. RNA crystallography is particularly arduous due to several factors such as RNA's paucity of surface chemical diversity, lability, repetitive anionic backbone, and flexibility, all of which are counterproductive to crystal packing. Here we describe Fab chaperone assisted RNA crystallography (CARC), a systematic technique to increase RNA crystallography success by facilitating crystal packing as well as expediting phase determination through molecular replacement of conserved Fab domains. Major steps described in this chapter include selection of a synthetic Fab library displayed on M13 phage against a structured RNA crystallization target, ELISA for initial choice of binding Fabs, Fab expression followed by protein A affinity then cation exchange chromatography purification, final choice of Fab by binding specificity and affinity as determined by a dot blot assay, and lastly gel filtration purification of a large quantity of chosen Fabs for crystallization.

Molecular self-assembly in substituted alanine derivatives: XRD, Hirshfeld surfaces and DFT studies

NASA Astrophysics Data System (ADS)

Rajalakshmi, Periasamy; Srinivasan, Navaneethakrishnan; Sivaraman, Gandhi; Razak, Ibrahim Abdul; Rosli, Mohd Mustaqim; Krishnakumar, Rajaputi Venkatraman

2014-06-01

The molecular assemblage in the crystal structures of three modified chiral amino acids, two of which are isomeric D- and L-pairs boc-L-benzothienylalanine (BLA), boc-D-benzothienylalanine (BDA) and the other boc-D-naphthylalanine (NDA) differing from this pair very slightly in the chemical modification introduced, is accurately described. The aggregation of amino acid molecules is similar in all the crystals and may be described as a twisted double helical ladder in which two complementary long helical chains formed through O-H⋯O hydrogen bonds are interconnected through the characteristic head-to-tail N-H⋯O hydrogen bonds. Thus the molecular aggregation enabled through classical hydrogen bonds may be regarded as a mimic of the characteristic double helical structure of DNA. Also, precise structural information involving these amino acid molecules with lower symmetry exhibiting higher trigonal symmetry in their self-assembly is expected to throw light on the nature and strength of intermolecular interactions and their role in self-assembly of molecular aggregates, which are crucial in developing new or at least supplement existing crystal engineering strategies. Single crystal X-ray analysis and their electronic structures were calculated at the DFT level with a detailed analysis of Hirshfeld surfaces and fingerprint plots facilitating a comparison of intermolecular interactions in building different supramolecular architectures.

Thermoelectric-enhanced, liquid-based cooling of a multi-component electronic system

DOEpatents

Chainer, Timothy J; Graybill, David P; Iyengar, Madhusudan K; Kamath, Vinod; Kochuparambil, Bejoy J; Schmidt, Roger R; Steinke, Mark E

2015-11-10

Methods are provided for facilitating cooling of an electronic component. The methods include providing: a liquid-cooled structure, a thermal conduction path coupling the electronic component and the liquid-cooled structure, a coolant loop in fluid communication with a coolant-carrying channel of the liquid-cooled structure, and an outdoor-air-cooled heat exchange unit coupled to facilitate heat transfer from the liquid-cooled structure via, at least in part, the coolant loop. The thermoelectric array facilitates transfer of heat from the electronic component to the liquid-cooled structure, and the heat exchange unit cools coolant passing through the coolant loop by dissipating heat from the coolant to outdoor ambient air. In one implementation, temperature of coolant entering the liquid-cooled structure is greater than temperature of the outdoor ambient air to which heat is dissipated.

Thermoelectric-enhanced, liquid-based cooling of a multi-component electronic system

DOEpatents

Chainer, Timothy J; Graybill, David P; Iyengar, Madhusudan K; Kamath, Vinod; Kochuparambil, Bejoy J; Schmidt, Roger R; Steinke, Mark E

2015-05-12

Apparatus and method are provided for facilitating cooling of an electronic component. The apparatus includes a liquid-cooled structure, a thermal conduction path coupling the electronic component and the liquid-cooled structure, a coolant loop in fluid communication with a coolant-carrying channel of the liquid-cooled structure, and an outdoor-air-cooled heat exchange unit coupled to facilitate heat transfer from the liquid-cooled structure via, at least in part, the coolant loop. The thermoelectric array facilitates transfer of heat from the electronic component to the liquid-cooled structure, and the heat exchange unit cools coolant passing through the coolant loop by dissipating heat from the coolant to outdoor ambient air. In one implementation, temperature of coolant entering the liquid-cooled structure is greater than temperature of the outdoor ambient air to which heat is dissipated.

Recommendations for age-appropriate education of children and adolescents with diabetes and their parents in the European Union.

PubMed

Martin, Delphine; Lange, Karin; Sima, Alexandra; Kownatka, Dagmar; Skovlund, Søren; Danne, Thomas; Robert, Jean-Jacques

2012-09-01

Education is the keystone of diabetes care, and structured self-management education is the key to a successful outcome. Existing guidelines provide comprehensive guidance on the various aspects of education and offer general and organizational principles of education, detailed curricula at different ages and stages of diabetes, and recommendations on models, methods, and tools to attain educative objectives. The International Society for Pediatric and Adolescent Diabetes guidelines give the most elaborate and detailed descriptions and recommendations on the practice of education, which other national guidelines address on specific aspects of education and care. The aim of the work package on education developed by Better Control in Paediatric and Adolescent Diabetes in the European Union: Working to Create Centers of Reference (SWEET) project was not to generate new guidelines but to evaluate how the existing guidelines were implemented in some pediatric diabetes reference centers. The SWEET members have completed a questionnaire that elaborates on the many aspects of delivery of education. This survey highlights a profound diversity of practices across centers in Europe, in terms of organization as well as the practices and the content of initial and continuing education. A toolbox is being developed within SWEET to facilitate exchanges on all aspects of education and to establish a process of validation of materials, tools, written structured age-adjusted programs, and evaluation procedures for the education of children and adolescents with diabetes. © 2012 John Wiley & Sons A/S.

Facilitated diffusion in chromatin lattices: mechanistic diversity and regulatory potential.

PubMed

Kampmann, Martin

2005-08-01

The interaction between a protein and a specific DNA site is the molecular basis for vital processes in all organisms. Location of the DNA target site by the protein commonly involves facilitated diffusion. Mechanisms of facilitated diffusion vary among proteins; they include one- and two-dimensional sliding along DNA, direct transfer between uncorrelated sites, as well as combinations of these mechanisms. Facilitated diffusion has almost exclusively been studied in vitro. This review discusses facilitated diffusion in the context of the living cell and proposes a theoretical model for facilitated diffusion in chromatin lattices. Chromatin structure differentially affects proteins in different modes of diffusion. The interplay of facilitated diffusion and chromatin structure can determine the rate of protein association with the target site, the frequency of association-dissociation events at the target site, and, under particular conditions, the occupancy of the target site. Facilitated diffusion is required in vivo for efficient DNA repair and bacteriophage restriction and has potential roles in fine-tuning gene regulatory networks and kinetically compartmentalizing the eukaryotic nucleus.

An Advanced Multi-Sensor Acousto-Ultrasonic Structural Health Monitoring System: Development and Aerospace Demonstration.

PubMed

Smithard, Joel; Rajic, Nik; van der Velden, Stephen; Norman, Patrick; Rosalie, Cedric; Galea, Steve; Mei, Hanfei; Lin, Bin; Giurgiutiu, Victor

2017-07-20

A key longstanding objective of the Structural Health Monitoring (SHM) research community is to enable the embedment of SHM systems in high value assets like aircraft to provide on-demand damage detection and evaluation. As against traditional non-destructive inspection hardware, embedded SHM systems must be compact, lightweight, low-power and sufficiently robust to survive exposure to severe in-flight operating conditions. Typical Commercial-Off-The-Shelf (COTS) systems can be bulky, costly and are often inflexible in their configuration and/or scalability, which militates against in-service deployment. Advances in electronics have resulted in ever smaller, cheaper and more reliable components that facilitate the development of compact and robust embedded SHM systems, including for Acousto-Ultrasonics (AU), a guided plate-wave inspection modality that has attracted strong interest due mainly to its capacity to furnish wide-area diagnostic coverage with a relatively low sensor density. This article provides a detailed description of the development, testing and demonstration of a new AU interrogation system called the Acousto Ultrasonic Structural health monitoring Array Module⁺ (AUSAM⁺). This system provides independent actuation and sensing on four Piezoelectric Wafer Active Sensor (PWAS) elements with further sensing on four Positive Intrinsic Negative (PIN) photodiodes for intensity-based interrogation of Fiber Bragg Gratings (FBG). The paper details the development of a novel piezoelectric excitation amplifier, which, in conjunction with flexible acquisition-system architecture, seamlessly provides electromechanical impedance spectroscopy for PWAS diagnostics over the full instrument bandwidth of 50 KHz-5 MHz. The AUSAM⁺ functionality is accessed via a simple hardware object providing a myriad of custom software interfaces that can be adapted to suit the specific requirements of each individual application.

An Advanced Multi-Sensor Acousto-Ultrasonic Structural Health Monitoring System: Development and Aerospace Demonstration

PubMed Central

Smithard, Joel; Rajic, Nik; Norman, Patrick; Rosalie, Cedric; Galea, Steve; Mei, Hanfei; Lin, Bin; Giurgiutiu, Victor

2017-01-01

A key longstanding objective of the Structural Health Monitoring (SHM) research community is to enable the embedment of SHM systems in high value assets like aircraft to provide on-demand damage detection and evaluation. As against traditional non-destructive inspection hardware, embedded SHM systems must be compact, lightweight, low-power and sufficiently robust to survive exposure to severe in-flight operating conditions. Typical Commercial-Off-The-Shelf (COTS) systems can be bulky, costly and are often inflexible in their configuration and/or scalability, which militates against in-service deployment. Advances in electronics have resulted in ever smaller, cheaper and more reliable components that facilitate the development of compact and robust embedded SHM systems, including for Acousto-Ultrasonics (AU), a guided plate-wave inspection modality that has attracted strong interest due mainly to its capacity to furnish wide-area diagnostic coverage with a relatively low sensor density. This article provides a detailed description of the development, testing and demonstration of a new AU interrogation system called the Acousto Ultrasonic Structural health monitoring Array Module+ (AUSAM+). This system provides independent actuation and sensing on four Piezoelectric Wafer Active Sensor (PWAS) elements with further sensing on four Positive Intrinsic Negative (PIN) photodiodes for intensity-based interrogation of Fiber Bragg Gratings (FBG). The paper details the development of a novel piezoelectric excitation amplifier, which, in conjunction with flexible acquisition-system architecture, seamlessly provides electromechanical impedance spectroscopy for PWAS diagnostics over the full instrument bandwidth of 50 KHz–5 MHz. The AUSAM+ functionality is accessed via a simple hardware object providing a myriad of custom software interfaces that can be adapted to suit the specific requirements of each individual application. PMID:28773193

Mechanism of Inhibition of Cholesteryl Ester Transfer Protein by Small Molecule Inhibitors.

PubMed

Chirasani, Venkat R; Sankar, Revathi; Senapati, Sanjib

2016-08-25

Cholesteryl ester transfer protein (CETP) facilitates the bidirectional exchange of cholesteryl esters and triglycerides between high-density lipoproteins and low- or very low-density lipoproteins. Recent studies have shown that the impairment of lipid exchange processes of CETP can be an effective strategy for the treatment of cardiovascular diseases (CVDs). Understanding the molecular mechanism of CETP inhibition has, therefore, attracted tremendous attention in recent past. In this study, we explored the detailed mechanism of CETP inhibition by a series of recently reported small molecule inhibitors that are currently under preclinical testing. Our results from molecular dynamics simulations and protein-ligand docking studies suggest that the hydrophobic interactions between the CETP core tunnel residues and inhibitor moieties play a pivotal role, and physical occlusion of the CETP tunnel by these small molecules is the primary mechanism of CETP inhibition. Interestingly, bound inhibitors were found to increase the plasticity of CETP, which was explained by principal component analysis that showed a larger space of sampling of CETP C-domain due to inhibitor binding. The atomic-level details presented here could help accelerate the structure-based drug-discovery processes targeting CETP for CVD therapeutics.

Wind Technology Modeling Within the System Advisor Model (SAM) (Poster)

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

Blair, N.; Dobos, A.; Ferguson, T.

This poster provides detail for implementation and the underlying methodology for modeling wind power generation performance in the National Renewable Energy Laboratory's (NREL's) System Advisor Model (SAM). SAM's wind power model allows users to assess projects involving one or more large or small wind turbines with any of the detailed options for residential, commercial, or utility financing. The model requires information about the wind resource, wind turbine specifications, wind farm layout (if applicable), and costs, and provides analysis to compare the absolute or relative impact of these inputs. SAM is a system performance and economic model designed to facilitate analysismore » and decision-making for project developers, financers, policymakers, and energy researchers. The user pairs a generation technology with a financing option (residential, commercial, or utility) to calculate the cost of energy over the multi-year project period. Specifically, SAM calculates the value of projects which buy and sell power at retail rates for residential and commercial systems, and also for larger-scale projects which operate through a power purchase agreement (PPA) with a utility. The financial model captures complex financing and rate structures, taxes, and incentives.« less

'Photosystem II: the water splitting enzyme of photosynthesis and the origin of oxygen in our atmosphere'.

PubMed

Barber, James

2016-01-01

About 3 billion years ago an enzyme emerged which would dramatically change the chemical composition of our planet and set in motion an unprecedented explosion in biological activity. This enzyme used solar energy to power the thermodynamically and chemically demanding reaction of water splitting. In so doing it provided biology with an unlimited supply of reducing equivalents needed to convert carbon dioxide into the organic molecules of life while at the same time produced oxygen to transform our planetary atmosphere from an anaerobic to an aerobic state. The enzyme which facilitates this reaction and therefore underpins virtually all life on our planet is known as Photosystem II (PSII). It is a pigment-binding, multisubunit protein complex embedded in the lipid environment of the thylakoid membranes of plants, algae and cyanobacteria. Today we have detailed understanding of the structure and functioning of this key and unique enzyme. The journey to this level of knowledge can be traced back to the discovery of oxygen itself in the 18th-century. Since then there has been a sequence of mile stone discoveries which makes a fascinating story, stretching over 200 years. But it is the last few years that have provided the level of detail necessary to reveal the chemistry of water oxidation and O-O bond formation. In particular, the crystal structure of the isolated PSII enzyme has been reported with ever increasing improvement in resolution. Thus the organisational and structural details of its many subunits and cofactors are now well understood. The water splitting site was revealed as a cluster of four Mn ions and a Ca ion surrounded by amino-acid side chains, of which seven provide direct ligands to the metals. The metal cluster is organised as a cubane structure composed of three Mn ions and a Ca2+ linked by oxo-bonds with the fourth Mn ion attached to the cubane. This structure has now been synthesised in a non-protein environment suggesting that it is a totally inorganic precursor for the evolution of the photosynthetic oxygen-evolving complex. In summary, the overall structure of the catalytic site has given a framework on which to build a mechanistic scheme for photosynthetic dioxygen generation and at the same time provide a blue-print and incentive to develop catalysts for artificial photo-electrochemical systems to split water and generate renewable solar fuels.

Accelerating biomedical innovation: a case study of the SPARK program at Stanford University, School of Medicine.

PubMed

Kim, Esther S; Omura, Paige M C; Lo, Andrew W

2017-07-01

Translating academic medical research into new therapies is an important challenge for the biopharmaceutical industry and investment communities, which have historically favored later-stage assets with lower risk and clearer commercial value. The Stanford SPARK program is an innovative model for addressing this challenge. The program was created in 2006 to educate students and faculty about bringing academic research from bench to bedside. Every year, the program provides mentorship and funding for approximately a dozen SPARK 'scholars,' with a focus on impacting patient lives, regardless of economic factors. By reviewing the detailed structure, function and operation of SPARK we hope to provide a template for other universities and institutions interested in de-risking and facilitating the translation of biomedical research. Copyright © 2017 Elsevier Ltd. All rights reserved.

Complement, a target for therapy in inflammatory and degenerative diseases.

PubMed

Morgan, B Paul; Harris, Claire L

2015-12-01

The complement system is a key innate immune defence against infection and an important driver of inflammation; however, these very properties can also cause harm. Inappropriate or uncontrolled activation of complement can cause local and/or systemic inflammation, tissue damage and disease. Complement provides numerous options for drug development as it is a proteolytic cascade that involves nine specific proteases, unique multimolecular activation and lytic complexes, an arsenal of natural inhibitors, and numerous receptors that bind to activation fragments. Drug design is facilitated by the increasingly detailed structural understanding of the molecules involved in the complement system. Only two anti-complement drugs are currently on the market, but many more are being developed for diseases that include infectious, inflammatory, degenerative, traumatic and neoplastic disorders. In this Review, we describe the history, current landscape and future directions for anti-complement therapies.

Computer-assisted knowledge acquisition for hypermedia systems

NASA Technical Reports Server (NTRS)

Steuck, Kurt

1990-01-01

The usage of procedural and declarative knowledge to set up the structure or 'web' of a hypermedia environment is described. An automated knowledge acquisition tool was developed that helps a knowledge engineer elicit and represent an expert's knowledge involved in performing procedural tasks. The tool represents both procedural and prerequisite, declarative knowledge that supports each activity performed by the expert. This knowledge is output and subsequently read by a hypertext scripting language to generate the link between blank, but labeled cards. Each step of the expert's activity and each piece of supporting declarative knowledge is set up as an empty node. An instructional developer can then enter detailed instructional material concerning each step and declarative knowledge into these empty nodes. Other research is also described that facilitates the translation of knowledge from one form into a form more readily useable by computerized systems.

LINE-1 Cultured Cell Retrotransposition Assay

PubMed Central

Kopera, Huira C.; Larson, Peter A.; Moldovan, John B.; Richardson, Sandra R.; Liu, Ying; Moran, John V.

2016-01-01

Summary The Long INterspersed Element-1 (LINE-1 or L1) retrotransposition assay has facilitated the discovery and characterization of active (i.e., retrotransposition-competent) LINE-1 sequences from mammalian genomes. In this assay, an engineered LINE-1 containing a retrotransposition reporter cassette is transiently transfected into a cultured cell line. Expression of the reporter cassette, which occurs only after a successful round of retrotransposition, allows the detection and quantification of the LINE-1 retrotransposition efficiency. This assay has yielded insight into the mechanism of LINE-1 retrotransposition. It also has provided a greater understanding of how the cell regulates LINE-1 retrotransposition and how LINE-1 retrotransposition impacts the structure of mammalian genomes. Below, we provide a brief introduction to LINE-1 biology and then detail how the LINE-1 retrotransposition assay is performed in cultured mammalian cells. PMID:26895052

An automated Genomes-to-Natural Products platform (GNP) for the discovery of modular natural products.

PubMed

Johnston, Chad W; Skinnider, Michael A; Wyatt, Morgan A; Li, Xiang; Ranieri, Michael R M; Yang, Lian; Zechel, David L; Ma, Bin; Magarvey, Nathan A

2015-09-28

Bacterial natural products are a diverse and valuable group of small molecules, and genome sequencing indicates that the vast majority remain undiscovered. The prediction of natural product structures from biosynthetic assembly lines can facilitate their discovery, but highly automated, accurate, and integrated systems are required to mine the broad spectrum of sequenced bacterial genomes. Here we present a genome-guided natural products discovery tool to automatically predict, combinatorialize and identify polyketides and nonribosomal peptides from biosynthetic assembly lines using LC-MS/MS data of crude extracts in a high-throughput manner. We detail the directed identification and isolation of six genetically predicted polyketides and nonribosomal peptides using our Genome-to-Natural Products platform. This highly automated, user-friendly programme provides a means of realizing the potential of genetically encoded natural products.

Desire Across Borders: markets, migration, and marital HIV risk in rural Mexico

PubMed Central

Hirsch, Jennifer S.

2014-01-01

This paper presents five concepts that articulate specific processes through which political and economic factors shape sexuality, drawing on ethnographic research on changing notions of marriage, love, and sexuality conducted in migrant-exporting rural Mexico and with Mexican migrants in Atlanta and New York. The first section describes how changing beliefs about love, marriage, sexual intimacy and fidelity constitute a cultural terrain which facilitates ‘vaginal marital bare backing’ in rural Mexico. The paper details sexual opportunity structures; sexual geographies; the multi-sectoral production of risk (including the ways in which housing, transportation, and other policy sectors together create the ‘recreation-deserts’ in which many migrants live); sexual projects, and externalities as conceptual tools that articulate how political and economic factors from the meso- to the macro-level shape sexuality. PMID:25343642

Virtual prototyping of drop test using explicit analysis

NASA Astrophysics Data System (ADS)

Todorov, Georgi; Kamberov, Konstantin

2017-12-01

Increased requirements for reliability and safety, included in contemporary standards and norms, has high impact over new product development. New numerical techniques based on virtual prototyping technology, facilitates imrpoving product development cycle, resutling in reduced time/money spent for this stage as well as increased knowledge about certain failure mechanism. So called "drop test" became nearly a "must" step in development of any human operated product. This study aims to demonstrate dynamic behaviour assessment of a structure under impact loads, based on virtual prototyping using a typical nonlinear analysis - explicit dynamics. An example is presneted, based on a plastic container that is used as cartridge for a dispenser machine exposed to various work conditions. Different drop orientations were analyzed and critical load cases and design weaknesses have been found. Several design modifications have been proposed, based on detailed analyses results review.

Cosmogony as an extrapolation of magnetospheric research

NASA Technical Reports Server (NTRS)

Alfven, H.

1984-01-01

A theory of the origin and evolution of the Solar System which considered electromagnetic forces and plasma effects is revised in light of information supplied by space research. In situ measurements in the magnetospheres and solar wind can be extrapolated outwards in space, to interstellar clouds, and backwards in time, to the formation of the solar system. The first extrapolation leads to a revision of cloud properties essential for the early phases in the formation of stars and solar nebulae. The latter extrapolation facilitates analysis of the cosmogonic processes by extrapolation of magnetospheric phenomena. Pioneer-Voyager observations of the Saturnian rings indicate that essential parts of their structure are fossils from cosmogonic times. By using detailed information from these space missions, it is possible to reconstruct events 4 to 5 billion years ago with an accuracy of a few percent.

Rules of Engagement: The Type VI Secretion System in Vibrio cholerae.

PubMed

Joshi, Avatar; Kostiuk, Benjamin; Rogers, Andrew; Teschler, Jennifer; Pukatzki, Stefan; Yildiz, Fitnat H

2017-04-01

Microbial species often exist in complex communities where they must avoid predation and compete for favorable niches. The type VI secretion system (T6SS) is a contact-dependent bacterial weapon that allows for direct killing of competitors through the translocation of proteinaceous toxins. Vibrio cholerae is a Gram-negative pathogen that can use its T6SS during antagonistic interactions with neighboring prokaryotic and eukaryotic competitors. The T6SS not only promotes V. cholerae's survival during its aquatic and host life cycles, but also influences its evolution by facilitating horizontal gene transfer. This review details the recent insights regarding the structure and function of the T6SS as well as the diverse signals and regulatory pathways that control its activation in V. cholerae. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ten steps to get started in Genome Assembly and Annotation

PubMed Central

Dominguez Del Angel, Victoria; Hjerde, Erik; Sterck, Lieven; Capella-Gutierrez, Salvadors; Notredame, Cederic; Vinnere Pettersson, Olga; Amselem, Joelle; Bouri, Laurent; Bocs, Stephanie; Klopp, Christophe; Gibrat, Jean-Francois; Vlasova, Anna; Leskosek, Brane L.; Soler, Lucile; Binzer-Panchal, Mahesh; Lantz, Henrik

2018-01-01

As a part of the ELIXIR-EXCELERATE efforts in capacity building, we present here 10 steps to facilitate researchers getting started in genome assembly and genome annotation. The guidelines given are broadly applicable, intended to be stable over time, and cover all aspects from start to finish of a general assembly and annotation project. Intrinsic properties of genomes are discussed, as is the importance of using high quality DNA. Different sequencing technologies and generally applicable workflows for genome assembly are also detailed. We cover structural and functional annotation and encourage readers to also annotate transposable elements, something that is often omitted from annotation workflows. The importance of data management is stressed, and we give advice on where to submit data and how to make your results Findable, Accessible, Interoperable, and Reusable (FAIR). PMID:29568489

Fundamental approaches in molecular biology for communication sciences and disorders.

PubMed

Bartlett, Rebecca S; Jetté, Marie E; King, Suzanne N; Schaser, Allison; Thibeault, Susan L

2012-08-01

This contemporary tutorial will introduce general principles of molecular biology, common deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and protein assays and their relevance in the field of communication sciences and disorders. Over the past 2 decades, knowledge of the molecular pathophysiology of human disease has increased at a remarkable pace. Most of this progress can be attributed to concomitant advances in basic molecular biology and, specifically, the development of an ever-expanding armamentarium of technologies for analysis of DNA, RNA, and protein structure and function. Details of these methodologies, their limitations, and examples from the communication sciences and disorders literature are presented. Results/Conclusions The use of molecular biology techniques in the fields of speech, language, and hearing sciences is increasing, facilitating the need for an understanding of molecular biology fundamentals and common experimental assays.

BIOSPIDA: A Relational Database Translator for NCBI

PubMed Central

Hagen, Matthew S.; Lee, Eva K.

2010-01-01

As the volume and availability of biological databases continue widespread growth, it has become increasingly difficult for research scientists to identify all relevant information for biological entities of interest. Details of nucleotide sequences, gene expression, molecular interactions, and three-dimensional structures are maintained across many different databases. To retrieve all necessary information requires an integrated system that can query multiple databases with minimized overhead. This paper introduces a universal parser and relational schema translator that can be utilized for all NCBI databases in Abstract Syntax Notation (ASN.1). The data models for OMIM, Entrez-Gene, Pubmed, MMDB and GenBank have been successfully converted into relational databases and all are easily linkable helping to answer complex biological questions. These tools facilitate research scientists to locally integrate databases from NCBI without significant workload or development time. PMID:21347013

The Au(111)/IL interfacial nanostructure in the presence of precursors and its influence on the electrodeposition process.

PubMed

Borisenko, Natalia; Lahiri, Abhishek; Pulletikurthi, Giridhar; Cui, Tong; Carstens, Timo; Zahlbach, Janine; Atkin, Rob; Endres, Frank

2018-01-01

Ionic liquids have attracted significant interest as electrolytes for the electrodeposition of metals and semiconductors, but the details of the deposition processes are not yet well understood. In this paper, we give an overview of how the addition of various precursors (TaF 5 , SiCl 4 , and GaCl 3 ) affects the solid/IL interfacial structure. In situ Atomic Force Microscopy (AFM) and vibrational spectroscopy have been employed to study the changes of the Au(111)/IL interface and in the electrolytes, respectively. Ionic liquids with the 1-butyl-1-methylpyrrolidinium ([Py 1,4 ] + ) cation and bis(trifluoromethylsulfonyl)amide ([TFSA] - ), trifluoromethylsulfonate ([TfO] - ) and tris(pentafluoroethyl)trifluorophosphate ([FAP] - ) as anions were chosen for this purpose. In situ AFM force-distance measurements reveal that both the anion of the IL and the solutes (TaF 5 or GaCl 3 ) influence the Electrical Double Layer (EDL) structure of the Au(111)/IL interface, which can affect the deposition process of Ta and the morphology of the Ga electrodeposits, respectively. Furthermore, the concentration of the precursor can significantly alter the Au(111)/[Py 1,4 ][FAP]-SiCl 4 interfacial structure wherein the presence of 0.25 M SiCl 4 a double layer structure forms that facilitates Si deposition. This study may provide some critical insights into the structure of the electrode/IL interface for specific applications.

Whose statistical reasoning is facilitated by a causal structure intervention?

PubMed

McNair, Simon; Feeney, Aidan

2015-02-01

People often struggle when making Bayesian probabilistic estimates on the basis of competing sources of statistical evidence. Recently, Krynski and Tenenbaum (Journal of Experimental Psychology: General, 136, 430-450, 2007) proposed that a causal Bayesian framework accounts for peoples' errors in Bayesian reasoning and showed that, by clarifying the causal relations among the pieces of evidence, judgments on a classic statistical reasoning problem could be significantly improved. We aimed to understand whose statistical reasoning is facilitated by the causal structure intervention. In Experiment 1, although we observed causal facilitation effects overall, the effect was confined to participants high in numeracy. We did not find an overall facilitation effect in Experiment 2 but did replicate the earlier interaction between numerical ability and the presence or absence of causal content. This effect held when we controlled for general cognitive ability and thinking disposition. Our results suggest that clarifying causal structure facilitates Bayesian judgments, but only for participants with sufficient understanding of basic concepts in probability and statistics.

Facilitating the Design of a Campus Leadership Team

ERIC Educational Resources Information Center

Meyers, Renee A.; Johnson, John R.

2008-01-01

This essay describes how we facilitated the design of a campus leadership team. What is particularly interesting about this consultative project is that both authors participated--one as facilitator and the other as participant. The facilitation included a needs assessment prior to the event, the use of structured controversy techniques,…

Imaging and Quantitation of a Succession of Transient Intermediates Reveal the Reversible Self-Assembly Pathway of a Simple Icosahedral Virus Capsid.

PubMed

Medrano, María; Fuertes, Miguel Ángel; Valbuena, Alejandro; Carrillo, Pablo J P; Rodríguez-Huete, Alicia; Mateu, Mauricio G

2016-11-30

Understanding the fundamental principles underlying supramolecular self-assembly may facilitate many developments, from novel antivirals to self-organized nanodevices. Icosahedral virus particles constitute paradigms to study self-assembly using a combination of theory and experiment. Unfortunately, assembly pathways of the structurally simplest virus capsids, those more accessible to detailed theoretical studies, have been difficult to study experimentally. We have enabled the in vitro self-assembly under close to physiological conditions of one of the simplest virus particles known, the minute virus of mice (MVM) capsid, and experimentally analyzed its pathways of assembly and disassembly. A combination of electron microscopy and high-resolution atomic force microscopy was used to structurally characterize and quantify a succession of transient assembly and disassembly intermediates. The results provided an experiment-based model for the reversible self-assembly pathway of a most simple (T = 1) icosahedral protein shell. During assembly, trimeric capsid building blocks are sequentially added to the growing capsid, with pentamers of building blocks and incomplete capsids missing one building block as conspicuous intermediates. This study provided experimental verification of many features of self-assembly of a simple T = 1 capsid predicted by molecular dynamics simulations. It also demonstrated atomic force microscopy imaging and automated analysis, in combination with electron microscopy, as a powerful single-particle approach to characterize at high resolution and quantify transient intermediates during supramolecular self-assembly/disassembly reactions. Finally, the efficient in vitro self-assembly achieved for the oncotropic, cell nucleus-targeted MVM capsid may facilitate its development as a drug-encapsidating nanoparticle for anticancer targeted drug delivery.

Evolution of coreceptor utilization to escape CCR5 antagonist therapy.

PubMed

Zhang, Jie; Gao, Xiang; Martin, John; Rosa, Bruce; Chen, Zheng; Mitreva, Makedonka; Henrich, Timothy; Kuritzkes, Daniel; Ratner, Lee

2016-07-01

The HIV-1 envelope interacts with coreceptors CCR5 and CXCR4 in a dynamic, multi-step process, its molecular details not clearly delineated. Use of CCR5 antagonists results in tropism shift and therapeutic failure. Here we describe a novel approach using full-length patient-derived gp160 quasispecies libraries cloned into HIV-1 molecular clones, their separation based on phenotypic tropism in vitro, and deep sequencing of the resultant variants for structure-function analyses. Analysis of functionally validated envelope sequences from patients who failed CCR5 antagonist therapy revealed determinants strongly associated with coreceptor specificity, especially at the gp120-gp41 and gp41-gp41 interaction surfaces that invite future research on the roles of subunit interaction and envelope trimer stability in coreceptor usage. This study identifies important structure-function relationships in HIV-1 envelope, and demonstrates proof of concept for a new integrated analysis method that facilitates laboratory discovery of resistant mutants to aid in development of other therapeutic agents. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Electron energy loss spectroscopy on semiconductor heterostructures for optoelectronics and photonics applications.

PubMed

Eljarrat, A; López-Conesa, L; Estradé, S; Peiró, F

2016-05-01

In this work, we present characterization methods for the analysis of nanometer-sized devices, based on silicon and III-V nitride semiconductor materials. These methods are devised in order to take advantage of the aberration corrected scanning transmission electron microscope, equipped with a monochromator. This set-up ensures the necessary high spatial and energy resolution for the characterization of the smallest structures. As with these experiments, we aim to obtain chemical and structural information, we use electron energy loss spectroscopy (EELS). The low-loss region of EELS is exploited, which features fundamental electronic properties of semiconductor materials and facilitates a high data throughput. We show how the detailed analysis of these spectra, using theoretical models and computational tools, can enhance the analytical power of EELS. In this sense, initially, results from the model-based fit of the plasmon peak are presented. Moreover, the application of multivariate analysis algorithms to low-loss EELS is explored. Finally, some physical limitations of the technique, such as spatial delocalization, are mentioned. © 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.

Spectroscopic and computational study of a nonheme iron nitrosyl center in a biosynthetic model of nitric oxide reductase.

PubMed

Chakraborty, Saumen; Reed, Julian; Ross, Matthew; Nilges, Mark J; Petrik, Igor D; Ghosh, Soumya; Hammes-Schiffer, Sharon; Sage, J Timothy; Zhang, Yong; Schulz, Charles E; Lu, Yi

2014-02-24

A major barrier to understanding the mechanism of nitric oxide reductases (NORs) is the lack of a selective probe of NO binding to the nonheme FeB center. By replacing the heme in a biosynthetic model of NORs, which structurally and functionally mimics NORs, with isostructural ZnPP, the electronic structure and functional properties of the FeB nitrosyl complex was probed. This approach allowed observation of the first S=3/2 nonheme {FeNO}(7) complex in a protein-based model system of NOR. Detailed spectroscopic and computational studies show that the electronic state of the {FeNO}(7) complex is best described as a high spin ferrous iron (S=2) antiferromagnetically coupled to an NO radical (S=1/2) [Fe(2+)-NO(.)]. The radical nature of the FeB -bound NO would facilitate N-N bond formation by radical coupling with the heme-bound NO. This finding, therefore, supports the proposed trans mechanism of NO reduction by NORs. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Preferential melting of secondary structures during protein unfolding in different solvents: Competition between hydrophobic solvation and hydrogen bonding

NASA Astrophysics Data System (ADS)

Bagchi, Biman; Roy, Susmita; Ghosh, Rikhia

2014-03-01

Aqueous binary mixtures such as water-DMSO, water-urea, and water-ethanol are known to serve as denaturants of a host of proteins, although the detailed mechanism is often not known. Here we combine studies on several proteins in multiple binary mixtures to obtain a unified understanding of the phenomenon. We compare with experiments to support the simulation findings. The proteins considered include (i) chicken villin head piece (HP-36), (ii) immunoglobulin binding protein G (GB1), (iii) myoglobin and (iv) lysozyme. We find that for amphiphilic solvents like DMSO, the hydrophobic groups and the strong hydrogen bonding ability of the >S =O oxygen atom act together to facilitate the unfolding. However, the hydrophilic solvents like urea, due to the presence of more hydrophilic ends (C =O and two NH2) has a high propensity of forming hydrogen bonds with the side-chain residues and backbone of beta-sheet than the same of alpha helix. Such diversity among the unfolding pathways of a given protein in different chemical environments is especially characterized by the preferential solvation of a particular secondary structure.

A comparative study of free oligosaccharides in the milk of domestic animals.

PubMed

Albrecht, Simone; Lane, Jonathan A; Mariño, Karina; Al Busadah, Khalid A; Carrington, Stephen D; Hickey, Rita M; Rudd, Pauline M

2014-04-14

The present study was conducted to obtain a comprehensive overview of oligosaccharides present in the milk of a variety of important domestic animals including cows, goats, sheep, pigs, horses and dromedary camels. Using an analytical workflow that included ultra-performance liquid chromatography-hydrophilic interaction liquid chromatography with fluorescence detection coupled to quadrupole time-of-flight MS, detailed oligosaccharide libraries were established. The partial or full characterisation of the neutral/fucosylated, phosphorylated and sialylated structures was facilitated by sequencing with linkage- and sugar-specific exoglycosidases. Relative peak quantification of the 2-aminobenzamide-labelled oligosaccharides provided additional information. Milk from domestic animals contained a much larger variety of complex oligosaccharides than was previously assumed, and thirteen of these structures have been identified previously in human milk. The direct comparison of the oligosaccharide mixtures reflects their role in the postnatal maturation of different types of gastrointestinal systems, which, in this way, are prepared for certain post-weaning diets. The potential value of animal milk for the commercial extraction of oligosaccharides to be used in human and animal health is highlighted.

sc-PDB: a database for identifying variations and multiplicity of 'druggable' binding sites in proteins.

PubMed

Meslamani, Jamel; Rognan, Didier; Kellenberger, Esther

2011-05-01

The sc-PDB database is an annotated archive of druggable binding sites extracted from the Protein Data Bank. It contains all-atoms coordinates for 8166 protein-ligand complexes, chosen for their geometrical and physico-chemical properties. The sc-PDB provides a functional annotation for proteins, a chemical description for ligands and the detailed intermolecular interactions for complexes. The sc-PDB now includes a hierarchical classification of all the binding sites within a functional class. The sc-PDB entries were first clustered according to the protein name indifferent of the species. For each cluster, we identified dissimilar sites (e.g. catalytic and allosteric sites of an enzyme). SCOPE AND APPLICATIONS: The classification of sc-PDB targets by binding site diversity was intended to facilitate chemogenomics approaches to drug design. In ligand-based approaches, it avoids comparing ligands that do not share the same binding site. In structure-based approaches, it permits to quantitatively evaluate the diversity of the binding site definition (variations in size, sequence and/or structure). The sc-PDB database is freely available at: http://bioinfo-pharma.u-strasbg.fr/scPDB.

Computational study of aggregation mechanism in human lysozyme[D67H

PubMed Central

Patel, Dharmeshkumar

2017-01-01

Aggregation of proteins is an undesired phenomena that affects both human health and bioengineered products such as therapeutic proteins. Finding preventative measures could be facilitated by a molecular-level understanding of dimer formation, which is the first step in aggregation. Here we present a molecular dynamics (MD) study of dimer formation propensity in human lysozyme and its D67H variant. Because the latter protein aggregates while the former does not, they offer an ideal system for testing the feasibility of the proposed MD approach which comprises three stages: i) partially unfolded conformers involved in dimer formation are generated via high-temperature MD simulations, ii) potential dimer structures are searched using docking and refined with MD, iii) free energy calculations are performed to find the most stable dimer structure. Our results provide a detailed explanation for how a single mutation (D67H) turns human lysozyme from non-aggregating to an aggregating protein. Conversely, the proposed method can be used to identify the residues causing aggregation in a protein, which can be mutated to prevent it. PMID:28467454

Optimal Design and Damage Tolerance Verification of an Isogrid Structure for Helicopter Application

NASA Technical Reports Server (NTRS)

Baker, Donald J.; Fudge, Jack; Ambur, Damodar R.; Kassapoglou, Christos

2003-01-01

A composite isogrid panel design for application to a rotorcraft fuselage is presented. An optimum panel design for the lower fuselage of the rotorcraft that is subjected to combined in-plane compression and shear loads was generated using a design tool that utilizes a smeared-stiffener theory in conjunction with a genetic algorithm. A design feature was introduced along the edges of the panel that facilitates introduction of loads into the isogrid panel without producing undesirable local bending gradients. A low-cost manufacturing method for the isogrid panel that incorporates these design details is also presented. Axial compression tests were conducted on the undamaged and low-speed impact damaged panels to demonstrate the damage tolerance of this isogrid panel. A combined loading test fixture was designed and utilized that allowed simultaneous application of compression and shear loads to the test specimen. Results from finite element analyses are presented for the isogrid panel designs and these results are compared with experimental results. This study illustrates the isogrid concept to be a viable candidate for application to the helicopter lower fuselage structure.

Fabrication of Carbohydrate Microarrays by Boronate Formation.

PubMed

Adak, Avijit K; Lin, Ting-Wei; Li, Ben-Yuan; Lin, Chun-Cheng

2017-01-01

The interactions between soluble carbohydrates and/or surface displayed glycans and protein receptors are essential to many biological processes and cellular recognition events. Carbohydrate microarrays provide opportunities for high-throughput quantitative analysis of carbohydrate-protein interactions. Over the past decade, various techniques have been implemented for immobilizing glycans on solid surfaces in a microarray format. Herein, we describe a detailed protocol for fabricating carbohydrate microarrays that capitalizes on the intrinsic reactivity of boronic acid toward carbohydrates to form stable boronate diesters. A large variety of unprotected carbohydrates ranging in structure from simple disaccharides and trisaccharides to considerably more complex human milk and blood group (oligo)saccharides have been covalently immobilized in a single step on glass slides, which were derivatized with high-affinity boronic acid ligands. The immobilized ligands in these microarrays maintain the receptor-binding activities including those of lectins and antibodies according to the structures of their pendant carbohydrates for rapid analysis of a number of carbohydrate-recognition events within 30 h. This method facilitates the direct construction of otherwise difficult to obtain carbohydrate microarrays from underivatized glycans.

Energetics of proton release on the first oxidation step in the water-oxidizing enzyme.

PubMed

Saito, Keisuke; Rutherford, A William; Ishikita, Hiroshi

2015-10-07

In photosystem II (PSII), the Mn4CaO5 cluster catalyses the water splitting reaction. The crystal structure of PSII shows the presence of a hydrogen-bonded water molecule directly linked to O4. Here we show the detailed properties of the H-bonds associated with the Mn4CaO5 cluster using a quantum mechanical/molecular mechanical approach. When O4 is taken as a μ-hydroxo bridge acting as a hydrogen-bond donor to water539 (W539), the S0 redox state best describes the unusually short O4-OW539 distance (2.5 Å) seen in the crystal structure. We find that in S1, O4 easily releases the proton into a chain of eight strongly hydrogen-bonded water molecules. The corresponding hydrogen-bond network is absent for O5 in S1. The present study suggests that the O4-water chain could facilitate the initial deprotonation event in PSII. This unexpected insight is likely to be of real relevance to mechanistic models for water oxidation.

A Plant's Response to Gravity as a Wave Guide Phenomenon

NASA Astrophysics Data System (ADS)

Wagner, Orvin

1997-11-01

Plant experimental data provides a unifying wave theory (W-wave theory) for the growth and development of plants. A plant's response to gravity is an important aspect of this theory. It appears that a plant part is tuned to the angle with which it initially grew with respect to the gravitational field and changes produce correction responses. This is true because the velocity of W-waves (whose standing waves determine plant structure) within plant tissue is found to be different in different directions (angle a) with respect to the gravitational field. I found that there are preferred values of a, namely integral multiples of near 5 degrees for some plants. Conifers apparently are more sensitive to the gravitational field than deciduous trees, in the cases studied, so their structure is determined in more detail by the gravitational field. A plant's response to gravity appears to be a fundamental phenomenon and may provide a new model for gravity that can be experimentally verified in the laboratory. Along these same lines accelerometers placed in plant tissue indicate that plants produce gravity related forces that facilitate sap flow. See the

Discrete kinetic models from funneled energy landscape simulations.

PubMed

Schafer, Nicholas P; Hoffman, Ryan M B; Burger, Anat; Craig, Patricio O; Komives, Elizabeth A; Wolynes, Peter G

2012-01-01

A general method for facilitating the interpretation of computer simulations of protein folding with minimally frustrated energy landscapes is detailed and applied to a designed ankyrin repeat protein (4ANK). In the method, groups of residues are assigned to foldons and these foldons are used to map the conformational space of the protein onto a set of discrete macrobasins. The free energies of the individual macrobasins are then calculated, informing practical kinetic analysis. Two simple assumptions about the universality of the rate for downhill transitions between macrobasins and the natural local connectivity between macrobasins lead to a scheme for predicting overall folding and unfolding rates, generating chevron plots under varying thermodynamic conditions, and inferring dominant kinetic folding pathways. To illustrate the approach, free energies of macrobasins were calculated from biased simulations of a non-additive structure-based model using two structurally motivated foldon definitions at the full and half ankyrin repeat resolutions. The calculated chevrons have features consistent with those measured in stopped flow chemical denaturation experiments. The dominant inferred folding pathway has an "inside-out", nucleation-propagation like character.

3D Printing of Biomolecular Models for Research and Pedagogy

PubMed Central

Da Veiga Beltrame, Eduardo; Tyrwhitt-Drake, James; Roy, Ian; Shalaby, Raed; Suckale, Jakob; Pomeranz Krummel, Daniel

2017-01-01

The construction of physical three-dimensional (3D) models of biomolecules can uniquely contribute to the study of the structure-function relationship. 3D structures are most often perceived using the two-dimensional and exclusively visual medium of the computer screen. Converting digital 3D molecular data into real objects enables information to be perceived through an expanded range of human senses, including direct stereoscopic vision, touch, and interaction. Such tangible models facilitate new insights, enable hypothesis testing, and serve as psychological or sensory anchors for conceptual information about the functions of biomolecules. Recent advances in consumer 3D printing technology enable, for the first time, the cost-effective fabrication of high-quality and scientifically accurate models of biomolecules in a variety of molecular representations. However, the optimization of the virtual model and its printing parameters is difficult and time consuming without detailed guidance. Here, we provide a guide on the digital design and physical fabrication of biomolecule models for research and pedagogy using open source or low-cost software and low-cost 3D printers that use fused filament fabrication technology. PMID:28362403

Effect of Secondary Doping Using Sorbitol on Structure and Transport Properties of PEDOT-PSS Thin Films

NASA Astrophysics Data System (ADS)

Khasim, Syed; Pasha, Apsar; Roy, Aashish S.; Parveen, Ameena; Badi, Nacer

2017-07-01

Poly(3,4-ethylene dioxythiophene):poly(styrenesulphonate) (PEDOT-PSS) in the recent past has emerged as one of the most fascinating conducting polymers for many device applications. The unique feature of PEDOT-PSS is its transparency in the entire visible spectrum with excellent thermal stability. The PEDOT-PSS as prepared as an aqueous dispersion has very low conductivity, and it hinders the performance of a device. In this work we report the conductivity enhancement of PEDOT-PSS thin films through secondary doping using a polar organic solvent such as sorbitol. The mechanism of conductivity enhancement was studied through various physical and chemical characterizations. The effect of sorbitol concentration on structure and transport properties of PEDOT-PSS thin films was investigated in detail. The structural and morphological modifications in PEDOT-PSS due to the addition of sorbitol was studied through Fourier transform spectroscopy, Ultra Violet-visible spectroscopy, theromogravimetric analysis, scanning electron microscopy and atomic force microscopy. The interactions resulting from conformational changes of PEDOT chains that changes from coiled to linear structure due to the sorbitol treatment significantly improves the conductivity of PEDOT-PSS films. The secondary doping of sorbitol reduces the energy barrier that facilitates the charge carrier hopping leading to enhanced conductivity. We have observed that the conductivity of PEDOT-PSS thin films was increased by two fold due to sorbitol treatment when compared to conductivity of pure PEDOT-PSS. We have carried out detailed analysis of dielectric parameters of sorbitol-treated PEDOT-PSS films and found that sorbitol treatment has a significant effect on various dielectric attributes of PEDOT-PSS films. Hence, secondary doping using sorbitol could be a useful way to effectively tailor the conductivity and dielectric properties of PEDOT-PSS thin films that can be used as flexible electrodes in optoelectronic devices.

78 FR 34893 - Drawbridge Operation Regulations; Reynolds Channel, Lawrence, NY

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-11

... under an alternate schedule for 176 days, to facilitate electrical and structural rehabilitation at the.... Judy Leung-Yee, Project Officer, First Coast Guard District, telephone (212) 668-7165, email judy.k... temporary deviation to facilitate electrical and structural rehabilitation at the bridge. The waterway has...

Assessing Facilitator Performance as an Influence on Student Satisfaction

ERIC Educational Resources Information Center

Dunlap, Scotty; May, David

2011-01-01

Growth in class size within the online environment has resulted in a facilitator model in which an instructor teaches the class with the assistance of facilitators who interact with students in smaller groups. This research sought to determine the effectiveness of a structured performance evaluation for facilitators and the correlation to student…

LED traffic signal replacement schedules : facilitating smooth freight flows.

DOT National Transportation Integrated Search

2011-11-01

This research details a field study of LED traffic signals in Missouri and develops a replacement schedule based on key findings. : Rates of degradation were statistically analyzed using Analysis of Variance (ANOVA). Results of this research will pro...

Evaluation of bridge deck with shrinkage-compensating concrete : VCTIR report detail.

DOT National Transportation Integrated Search

2016-01-01

Concrete bridge decks are susceptible to premature cracking and to corrosion of reinforcing steel. Low-permeability concrete does not always ensure durability if the concrete has excessive cracks that facilitate the intrusion of aggressive solutions....

Data model and relational database design for the New England Water-Use Data System (NEWUDS)

USGS Publications Warehouse

Tessler, Steven

2001-01-01

The New England Water-Use Data System (NEWUDS) is a database for the storage and retrieval of water-use data. NEWUDS can handle data covering many facets of water use, including (1) tracking various types of water-use activities (withdrawals, returns, transfers, distributions, consumptive-use, wastewater collection, and treatment); (2) the description, classification and location of places and organizations involved in water-use activities; (3) details about measured or estimated volumes of water associated with water-use activities; and (4) information about data sources and water resources associated with water use. In NEWUDS, each water transaction occurs unidirectionally between two site objects, and the sites and conveyances form a water network. The core entities in the NEWUDS model are site, conveyance, transaction/rate, location, and owner. Other important entities include water resources (used for withdrawals and returns), data sources, and aliases. Multiple water-exchange estimates can be stored for individual transactions based on different methods or data sources. Storage of user-defined details is accommodated for several of the main entities. Numerous tables containing classification terms facilitate detailed descriptions of data items and can be used for routine or custom data summarization. NEWUDS handles single-user and aggregate-user water-use data, can be used for large or small water-network projects, and is available as a stand-alone Microsoft? Access database structure. Users can customize and extend the database, link it to other databases, or implement the design in other relational database applications.

Chlamydia trachomatis CT771 (nudH) is an asymmetric Ap4A hydrolase.

PubMed

Barta, Michael L; Lovell, Scott; Sinclair, Amy N; Battaile, Kevin P; Hefty, P Scott

2014-01-14

Asymmetric diadenosine 5',5‴-P(1),P(4)-tetraphosphate (Ap4A) hydrolases are members of the Nudix superfamily that asymmetrically cleave the metabolite Ap4A into ATP and AMP while facilitating homeostasis. The obligate intracellular mammalian pathogen Chlamydia trachomatis possesses a single Nudix family protein, CT771. As pathogens that rely on a host for replication and dissemination typically have one or zero Nudix family proteins, this suggests that CT771 could be critical for chlamydial biology and pathogenesis. We identified orthologues to CT771 within environmental Chlamydiales that share active site residues suggesting a common function. Crystal structures of both apo- and ligand-bound CT771 were determined to 2.6 Å and 1.9 Å resolution, respectively. The structure of CT771 shows a αβα-sandwich motif with many conserved elements lining the putative Nudix active site. Numerous aspects of the ligand-bound CT771 structure mirror those observed in the ligand-bound structure of the Ap4A hydrolase from Caenorhabditis elegans. These structures represent only the second Ap4A hydrolase enzyme member determined from eubacteria and suggest that mammalian and bacterial Ap4A hydrolases might be more similar than previously thought. The aforementioned structural similarities, in tandem with molecular docking, guided the enzymatic characterization of CT771. Together, these studies provide the molecular details for substrate binding and specificity, supporting the analysis that CT771 is an Ap4A hydrolase (nudH).

Combined protein construct and synthetic gene engineering for heterologous protein expression and crystallization using Gene Composer

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

Raymond, Amy; Lovell, Scott; Lorimer, Don

2009-12-01

With the goal of improving yield and success rates of heterologous protein production for structural studies we have developed the database and algorithm software package Gene Composer. This freely available electronic tool facilitates the information-rich design of protein constructs and their engineered synthetic gene sequences, as detailed in the accompanying manuscript. In this report, we compare heterologous protein expression levels from native sequences to that of codon engineered synthetic gene constructs designed by Gene Composer. A test set of proteins including a human kinase (P38{alpha}), viral polymerase (HCV NS5B), and bacterial structural protein (FtsZ) were expressed in both E. colimore » and a cell-free wheat germ translation system. We also compare the protein expression levels in E. coli for a set of 11 different proteins with greatly varied G:C content and codon bias. The results consistently demonstrate that protein yields from codon engineered Gene Composer designs are as good as or better than those achieved from the synonymous native genes. Moreover, structure guided N- and C-terminal deletion constructs designed with the aid of Gene Composer can lead to greater success in gene to structure work as exemplified by the X-ray crystallographic structure determination of FtsZ from Bacillus subtilis. These results validate the Gene Composer algorithms, and suggest that using a combination of synthetic gene and protein construct engineering tools can improve the economics of gene to structure research.« less

Graduate teaching assistants in a reformed introductory physics course: Synthesis of quantitative analyses of instructor action and qualitative analyses of instructor attitudes and perspectives

NASA Astrophysics Data System (ADS)

Calder, Austin Michael

Physics Education Research (PER) has shown us that when students have opportunities to make sense of concepts they tend to remember them better and can apply them more appropriately to new situations. PER has also revealed that an interactive, cooperative, small group environment is more conducive to achieving this than traditional lecture and recitation sections. It is useful to consider the aims of reformed instruction from the point of view of the graduate teaching assistants (GTAs) in physics, who are facilitating the instruction. The data in this dissertation comes from audio-recordings of GTAs teaching in an algebra-based introductory course; I develop a rubric for assessing the teaching practices of the GTAs which separates teaching into five categories according to the reformed practices present. The rubric and technique developed here could be used as a diagnostic for GTAs new to a reformed classroom. I also conducted surveys of the GTA participants, as well as semi-structured interviews to gain more information about the attitudes and perspectives toward reformed physics instruction. Results from this work include: (1) A diagnostic tool for teaching improvement and (2) a detailed understanding of the GTA facilitators' teaching practices in the reformed physics laboratory.

Sandbox rheometry: Co-evolution of stress and strain in Riedel- and Critical Wedge-experiments

NASA Astrophysics Data System (ADS)

Ritter, Malte C.; Santimano, Tasca; Rosenau, Matthias; Leever, Karen; Oncken, Onno

2018-01-01

Analogue sandbox experiments have been used for a long time to understand tectonic processes, because they facilitate detailed measurements of deformation at a spatio-temporal resolution unachievable from natural data. Despite this long history, force measurements to further characterise the mechanical evolution in analogue sandbox experiments have only emerged recently. Combined continuous measurements of forces and deformation in such experiments, an approach here referred to as "sandbox rheometry", are a new tool that may help to better understand work budgets and force balances for tectonic systems and to derive constitutive laws for regional scale deformation. In this article we present an experimental device that facilitates precise measurements of boundary forces and surface deformation at high temporal and spatial resolution. We demonstrate its capabilities in two classical experiments: one of strike-slip deformation (the Riedel set-up) and one of compressional accretionary deformation (the Critical Wedge set-up). In these we are able to directly observe a correlation between strain weakening and strain localisation that had previously only been inferred, namely the coincidence of the maximum localisation rate with the onset of weakening. Additionally, we observe in the compressional experiment a hysteresis of localisation with respect to the mechanical evolution that reflects the internal structural complexity of an accretionary wedge.

30 CFR 780.12 - Operation plan: Existing structures.

Code of Federal Regulations, 2010 CFR

2010-07-01

... each existing structure proposed to be used in connection with or to facilitate the surface coal mining... which describe its current condition; (3) Approximate dates on which construction of the existing... proposed to be modified or reconstructed for use in connection with or to facilitate the surface coal...

30 CFR 784.12 - Operation plan: Existing structures.

Code of Federal Regulations, 2010 CFR

2010-07-01

... each existing structure proposed to be used in connection with or to facilitate the surface coal mining... which describe its current condition; (3) Approximate dates on which construction of the existing... proposed to be modified or reconstructed for use in connection with or to facilitate the surface coal...

10 CFR 32.14 - Certain items containing byproduct material; requirements for license to apply or initially...

Code of Federal Regulations, 2010 CFR

2010-01-01

... maximum quantity of byproduct material in each product; (2) Details of construction and design of each... experimental studies and tests, required by the Commission to facilitate a determination of the safety of the...

NIH tools facilitate matching cancer drugs with gene targets

Cancer.gov

A new study details how a suite of web-based tools provides the research community with greatly improved capacity to compare data derived from large collections of genomic information against thousands of drugs. By comparing drugs and genetic targets, re

Methods for Computationally Efficient Structured CFD Simulations of Complex Turbomachinery Flows

NASA Technical Reports Server (NTRS)

Herrick, Gregory P.; Chen, Jen-Ping

2012-01-01

This research presents more efficient computational methods by which to perform multi-block structured Computational Fluid Dynamics (CFD) simulations of turbomachinery, thus facilitating higher-fidelity solutions of complicated geometries and their associated flows. This computational framework offers flexibility in allocating resources to balance process count and wall-clock computation time, while facilitating research interests of simulating axial compressor stall inception with more complete gridding of the flow passages and rotor tip clearance regions than is typically practiced with structured codes. The paradigm presented herein facilitates CFD simulation of previously impractical geometries and flows. These methods are validated and demonstrate improved computational efficiency when applied to complicated geometries and flows.

Using the stepladder technique to facilitate the performance of audioconferencing groups.

PubMed

Rogelberg, Steven G; O'Connor, Matthew S; Sederburg, Matthew

2002-10-01

Organizational workforces are becoming increasingly dispersed. To facilitate communications among individuals or groups of people located in a number of different locations, teleconferencing technologies, such as audioconferencing, have been developed. The authors examined whether a structural group intervention, the stepladder technique, can facilitate the task performance of 4-person groups (n = 52) when using audioconferencing. Consistent with research conducted on face-to-face groups, the stepladder technique was found to facilitate the decision-making performance of groups interacting via audioconference. The authors postulated that certain structural elements of the stepladder technique compensate for obstacles inherent in nonvisual communications. Supplementary analyses examined best member influence and the existence of order of entry effects into the stepladder process.

New families of human regulatory RNA structures identified by comparative analysis of vertebrate genomes.

PubMed

Parker, Brian J; Moltke, Ida; Roth, Adam; Washietl, Stefan; Wen, Jiayu; Kellis, Manolis; Breaker, Ronald; Pedersen, Jakob Skou

2011-11-01

Regulatory RNA structures are often members of families with multiple paralogous instances across the genome. Family members share functional and structural properties, which allow them to be studied as a whole, facilitating both bioinformatic and experimental characterization. We have developed a comparative method, EvoFam, for genome-wide identification of families of regulatory RNA structures, based on primary sequence and secondary structure similarity. We apply EvoFam to a 41-way genomic vertebrate alignment. Genome-wide, we identify 220 human, high-confidence families outside protein-coding regions comprising 725 individual structures, including 48 families with known structural RNA elements. Known families identified include both noncoding RNAs, e.g., miRNAs and the recently identified MALAT1/MEN β lincRNA family; and cis-regulatory structures, e.g., iron-responsive elements. We also identify tens of new families supported by strong evolutionary evidence and other statistical evidence, such as GO term enrichments. For some of these, detailed analysis has led to the formulation of specific functional hypotheses. Examples include two hypothesized auto-regulatory feedback mechanisms: one involving six long hairpins in the 3'-UTR of MAT2A, a key metabolic gene that produces the primary human methyl donor S-adenosylmethionine; the other involving a tRNA-like structure in the intron of the tRNA maturation gene POP1. We experimentally validate the predicted MAT2A structures. Finally, we identify potential new regulatory networks, including large families of short hairpins enriched in immunity-related genes, e.g., TNF, FOS, and CTLA4, which include known transcript destabilizing elements. Our findings exemplify the diversity of post-transcriptional regulation and provide a resource for further characterization of new regulatory mechanisms and families of noncoding RNAs.

Crystal structure of the human glucose transporter GLUT1

NASA Astrophysics Data System (ADS)

Deng, Dong; Xu, Chao; Sun, Pengcheng; Wu, Jianping; Yan, Chuangye; Hu, Mingxu; Yan, Nieng

2014-06-01

The glucose transporter GLUT1 catalyses facilitative diffusion of glucose into erythrocytes and is responsible for glucose supply to the brain and other organs. Dysfunctional mutations may lead to GLUT1 deficiency syndrome, whereas overexpression of GLUT1 is a prognostic indicator for cancer. Despite decades of investigation, the structure of GLUT1 remains unknown. Here we report the crystal structure of human GLUT1 at 3.2 Å resolution. The full-length protein, which has a canonical major facilitator superfamily fold, is captured in an inward-open conformation. This structure allows accurate mapping and potential mechanistic interpretation of disease-associated mutations in GLUT1. Structure-based analysis of these mutations provides an insight into the alternating access mechanism of GLUT1 and other members of the sugar porter subfamily. Structural comparison of the uniporter GLUT1 with its bacterial homologue XylE, a proton-coupled xylose symporter, allows examination of the transport mechanisms of both passive facilitators and active transporters.

Directly connected heat exchanger tube section and coolant-cooled structure

DOEpatents

Chainer, Timothy J.; Coico, Patrick A.; Graybill, David P.; Iyengar, Madhusudan K.; Kamath, Vinod; Kochuparambil, Bejoy J.; Schmidt, Roger R.; Steinke, Mark E.

2015-09-15

A method is provided for fabricating a cooling apparatus for cooling an electronics rack, which includes an air-to-liquid heat exchanger, one or more coolant-cooled structures, and a tube. The heat exchanger is associated with the electronics rack and disposed to cool air passing through the rack, includes a plurality of coolant-carrying tube sections, each tube section having a coolant inlet and outlet, one of which is coupled in fluid communication with a coolant loop to facilitate flow of coolant through the tube section. The coolant-cooled structure(s) is in thermal contact with an electronic component(s) of the rack, and facilitates transfer of heat from the component(s) to the coolant. The tube connects in fluid communication one coolant-cooled structure and the other of the coolant inlet or outlet of the one tube section, and facilitates flow of coolant directly between that coolant-carrying tube section of the heat exchanger and the coolant-cooled structure.

Directly connected heat exchanger tube section and coolant-cooled structure

DOEpatents

Chainer, Timothy J; Coico, Patrick A; Graybill, David P; Iyengar, Madhusudan K; Kamath, Vinod; Kochuparambil, Bejoy J; Schmidt, Roger R; Steinke, Mark E

2014-04-01

A cooling apparatus for an electronics rack is provided which includes an air-to-liquid heat exchanger, one or more coolant-cooled structures and a tube. The heat exchanger, which is associated with the electronics rack and disposed to cool air passing through the rack, includes a plurality of distinct, coolant-carrying tube sections, each tube section having a coolant inlet and a coolant outlet, one of which is coupled in fluid communication with a coolant loop to facilitate flow of coolant through the tube section. The coolant-cooled structure(s) is in thermal contact with an electronic component(s) of the rack, and facilitates transfer of heat from the component(s) to the coolant. The tube connects in fluid communication one coolant-cooled structure and the other of the coolant inlet or outlet of the one tube section, and facilitates flow of coolant directly between that coolant-carrying tube section of the heat exchanger and the coolant-cooled structure.

Content, Structure, and Sequence of the Detailing Discipline at Kendall College of Art and Design.

ERIC Educational Resources Information Center

Mulder, Bruce E.

A study identified the appropriate general content, structure, and sequence for a detailing discipline that promoted student achievement to professional levels. Its focus was the detailing discipline, a sequence of studio courses within the furniture design program at Kendall College of Art and Design, Grand Rapids, Michigan. (Detailing, an…

Respiratory analysis of coupled mitochondria in cryopreserved liver biopsies.

PubMed

García-Roche, Mercedes; Casal, Alberto; Carriquiry, Mariana; Radi, Rafael; Quijano, Celia; Cassina, Adriana

2018-07-01

The aim of this work was to develop a cryopreservation method of small liver biopsies for in situ mitochondrial function assessment. Herein we describe a detailed protocol for tissue collection, cryopreservation, high-resolution respirometry using complex I and II substrates, calculation and interpretation of respiratory parameters. Liver biopsies from cow and rat were sequentially frozen in a medium containing dimethylsulfoxide as cryoprotectant and stored for up to 3 months at -80 °C. Oxygen consumption rate studies of fresh and cryopreserved samples revealed that most respiratory parameters remained unchanged. Additionally, outer mitochondrial membrane integrity was assessed adding cytochrome c, proving that our cryopreservation method does not harm mitochondrial structure. In sum, we present a reliable way to cryopreserve small liver biopsies without affecting mitochondrial function. Our protocol will enable the transport and storage of samples, extending and facilitating mitochondrial function analysis of liver biopsies. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Defining Putative Glycan Cancer Biomarkers by Mass Spectrometry

PubMed Central

Mechref, Yehia; Hu, Yunli; Garcia, Aldo; Hussein, Ahmed

2013-01-01

Summary For decades, the association between aberrant glycosylation and many types of cancers has been shown. However, defining the changes of glycan structures has not been demonstrated until recently. This has been facilitated by the major advances in mass spectrometry and separation science which allowed the detailed characterization of glycan changes associated with cancer. Mass spectrometry glycomics methods have been successfully employed to compare the glycomic profiles of different human specimen collected from disease-free individuals and patients with cancer. Additionally, comparing the glycomic profiles of glycoproteins purified from specimen collected from disease-free individuals and patients with cancer has also been performed. These types of glycan analyses employing mass spectrometry or liquid-chromatography mass spectrometry allowed the characterization of native, labeled, and permethylated glycans. This review discusses the different glycomic and glycoproteomic methods employed for defining glycans as cancer biomarkers of different organs, including breast, colon, esophagus, liver, lung, ovarian, pancreas and prostate. PMID:23157355

Formation pathways of mesoporous silica nanoparticles with dodecagonal tiling

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

Sun, Yao; Ma, Kai; Kao, Teresa

Considerable progress in the fabrication of quasicrystals demonstrates that they can be realized in a broad range of materials. However, the development of chemistries enabling direct experimental observation of early quasicrystal growth pathways remains challenging. Here, we report the synthesis of four surfactant-directed mesoporous silica nanoparticle structures, including dodecagonal quasicrystalline nanoparticles, as a function of micelle pore expander concentration or stirring rate. We demonstrate that the early formation stages of dodecagonal quasicrystalline mesoporous silica nanoparticles can be preserved, where precise control of mesoporous silica nanoparticle size down to <30 nm facilitates comparison between mesoporous silica nanoparticles and simulated single-particle growthmore » trajectories beginning with a single tiling unit. Our results reveal details of the building block size distributions during early growth and how they promote quasicrystal formation. This work identifies simple synthetic parameters, such as stirring rate, that may be exploited to design other quasicrystal-forming self-assembly chemistries and processes.« less

Coding conventions and principles for a National Land-Change Modeling Framework

USGS Publications Warehouse

Donato, David I.

2017-07-14

This report establishes specific rules for writing computer source code for use with the National Land-Change Modeling Framework (NLCMF). These specific rules consist of conventions and principles for writing code primarily in the C and C++ programming languages. Collectively, these coding conventions and coding principles create an NLCMF programming style. In addition to detailed naming conventions, this report provides general coding conventions and principles intended to facilitate the development of high-performance software implemented with code that is extensible, flexible, and interoperable. Conventions for developing modular code are explained in general terms and also enabled and demonstrated through the appended templates for C++ base source-code and header files. The NLCMF limited-extern approach to module structure, code inclusion, and cross-module access to data is both explained in the text and then illustrated through the module templates. Advice on the use of global variables is provided.

JPL space robotics: Present accomplishments and future thrusts

NASA Astrophysics Data System (ADS)

Weisbin, C. R.; Hayati, S. A.; Rodriguez, G.

1994-10-01

Complex missions require routine and unscheduled inspection for safe operation. The purpose of research in this task is to facilitate structural inspection of the planned Space Station while mitigating the need for extravehicular activity (EVA), and giving the operator supervisory control over detailed and somewhat mundane, but important tasks. The telerobotic system enables inspection relative to a given reference (e.g., the status of the facility at the time of the last inspection) and alerts the operator to potential anomalies for verification and action. There are two primary objectives of this project: (1) To develop technologies that enable well-integrated NASA ground-to-orbit telerobotics operations, and (2) to develop a prototype common architecture workstation which implements these capabilities for other NASA technology projects and planned NASA flight applications. This task develops and supports three telerobot control modes which are applicable to time delay operation: Preview teleoperation, teleprogramming, and supervised autonomy.

Do the same traffic rules apply? Directional chromosome segregation by SpoIIIE and FtsK.

PubMed

Besprozvannaya, Marina; Burton, Briana M

2014-08-01

Over a decade of studies have tackled the question of how FtsK/SpoIIIE translocases establish and maintain directional DNA translocation during chromosome segregation in bacteria. FtsK/SpoIIIE translocases move DNA in a highly processive, directional manner, where directionality is facilitated by sequences on the substrate DNA molecules that are being transported. In recent years, structural, biochemical, single-molecule and high-resolution microscopic studies have provided new insight into the mechanistic details of directional DNA segregation. Out of this body of work, a series of models have emerged and, ultimately, yielded two seemingly opposing models: the loading model and the target search model. We review these recent mechanistic insights into directional DNA movement and discuss the data that may serve to unite these suggested models, as well as propose future directions that may ultimately solve the debate. © 2014 John Wiley & Sons Ltd.

Influences of geomorphology and geology on alpine treeline in the American West - More important than climatic influences?

USGS Publications Warehouse

Butler, D.R.; Malanson, G.P.; Walsh, S.J.; Fagre, D.B.

2007-01-01

The spatial distribution and pattern of alpine treeline in the American West reflect the overarching influences of geological history, lithology and structure, and geomorphic processes and landforms, and geologic and geomorphic factors—both forms and processes—can control the spatiotemporal response of the ecotone to climate change. These influences occur at spatial scales ranging from the continental scale to fine scale processes and landforms at the slope scale. Past geomorphic influences, particularly Pleistocene glaciation, have also left their impact on treeline, and treelines across the west are still adjusting to post-Pleistocene conditions within Pleistocene-created landforms. Current fine scale processes include solifluction and changes on relict solifluction and digging by animals. These processes should be examined in detail in future studies to facilitate a better understanding of where individual tree seedlings become established as a primary response of the ecotone to climate change.

Object-oriented software design in semiautomatic building extraction

NASA Astrophysics Data System (ADS)

Guelch, Eberhard; Mueller, Hardo

1997-08-01

Developing a system for semiautomatic building acquisition is a complex process, that requires constant integration and updating of software modules and user interfaces. To facilitate these processes we apply an object-oriented design not only for the data but also for the software involved. We use the unified modeling language (UML) to describe the object-oriented modeling of the system in different levels of detail. We can distinguish between use cases from the users point of view, that represent a sequence of actions, yielding in an observable result and the use cases for the programmers, who can use the system as a class library to integrate the acquisition modules in their own software. The structure of the system is based on the model-view-controller (MVC) design pattern. An example from the integration of automated texture extraction for the visualization of results demonstrate the feasibility of this approach.

Epigenomics, Pharmacoepigenomics, and Personalized Medicine in Cervical Cancer.

PubMed

Kabekkodu, Shama Prasada; Chakrabarty, Sanjiban; Ghosh, Supriti; Brand, Angela; Satyamoorthy, Kapaettu

2017-01-01

Epigenomics encompasses the study of genome-wide changes in DNA methylation, histone modifications and noncoding RNAs leading to altered transcription, chromatin structure, and posttranscription RNA processing, respectively, resulting in an altered rate of gene expression. The role of epigenetic modifications facilitating human diseases is well established. Previous studies have identified histone and cytosine code during normal and pathological conditions with special emphasis on how these modifications regulate transcriptional events. Recent studies have also mapped these epigenetic modification and pathways leading to carcinogenesis. Discovery of drugs that target proteins/enzymes in the epigenetic pathways may provide better therapeutic opportunities, and identification of such modulators for DNA methylation, histone modifications, and expression of noncoding RNAs for several cancer types is underway. In this review, we provide a detailed description of recent developments in the field of epigenetics and its impact on personalized medicine to manage cervical cancer. © 2017 S. Karger AG, Basel.

A sealable ultrathin window sample cell for the study of liquids by means of soft X-ray spectroscopy

NASA Astrophysics Data System (ADS)

Grötzsch, D.; Streeck, C.; Nietzold, C.; Malzer, W.; Mantouvalou, I.; Nutsch, A.; Dietrich, P.; Unger, W.; Beckhoff, B.; Kanngießer, B.

2017-12-01

A new sample cell concept for the analysis of liquids or solid-liquid interfaces using soft X-ray spectroscopy is presented, which enables the complete sealing of the cell as well as the transport into vacuum via, for example, a load-lock system. The cell uses pressure monitoring and active as well as passive pressure regulation systems, thereby facilitating the full control over the pressure during filling, sealing, evacuation, and measurement. The cell design and sample preparation as well as the crucial sealing procedure are explained in detail. As a first proof-of-principle experiment, successful nitrogen K-edge fluorescence yield near-edge X-ray absorption fine structure experiments of a biomolecular solution are presented. For this purpose, it is shown that the careful evaluation of all involved parameters, such as window type or photon flux, is desirable for optimizing the experimental result.

Formation pathways of mesoporous silica nanoparticles with dodecagonal tiling

DOE PAGES

Sun, Yao; Ma, Kai; Kao, Teresa; ...

2017-08-15

Considerable progress in the fabrication of quasicrystals demonstrates that they can be realized in a broad range of materials. However, the development of chemistries enabling direct experimental observation of early quasicrystal growth pathways remains challenging. Here, we report the synthesis of four surfactant-directed mesoporous silica nanoparticle structures, including dodecagonal quasicrystalline nanoparticles, as a function of micelle pore expander concentration or stirring rate. We demonstrate that the early formation stages of dodecagonal quasicrystalline mesoporous silica nanoparticles can be preserved, where precise control of mesoporous silica nanoparticle size down to <30 nm facilitates comparison between mesoporous silica nanoparticles and simulated single-particle growthmore » trajectories beginning with a single tiling unit. Our results reveal details of the building block size distributions during early growth and how they promote quasicrystal formation. This work identifies simple synthetic parameters, such as stirring rate, that may be exploited to design other quasicrystal-forming self-assembly chemistries and processes.« less

Thirteen years and counting: Outcomes of a concurrent ASN/BSN enrollment program.

PubMed

Heglund, Stephen; Simmons, Jessica; Wink, Diane; D'Meza Leuner, Jean

In their 2011 report, The Future of Nursing, the Institute of Medicine called for 80% of the nursing workforce to be comprised of baccalaureate prepared Registered Nurses by the year 2020. One suggested approach to achieve this goal is the creation of programs that allow students to progress through associate and baccalaureate nursing preparation simultaneously. This paper describes the University of Central Florida's 13-year experience after implementing a Concurrent Enrollment Program. Development and structure of the program, advisement and curriculum details, facilitators and barriers are described. Data on National Council Licensure Examination for Registered Nurses pass rates, completion rates, comparison with traditional RN-BSN students, and progression to graduate school are also included. The Concurrent Program model described here between a specific university and state college partners, demonstrated positive outcomes that support achievement of the Institute of Medicine's goals. Copyright © 2017 Elsevier Inc. All rights reserved.

NASA Workshop on Technology for Human Robotic Exploration and Development of Space

NASA Technical Reports Server (NTRS)

Mankins, J. C.; Marzwell, N.; Mullins, C. A.; Christensen, C. B.; Howell, J. T.; O'Neil, D. A.

2004-01-01

Continued constrained budgets and growing interests in the industrialization and development of space requires NASA to seize every opportunity for assuring the maximum return on space infrastructure investments. This workshop provided an excellent forum for reviewing, evaluating, and updating pertinent strategic planning, identifying advanced concepts and high-risk/high-leverage research and technology requirements, developing strategies and roadmaps, and establishing approaches, methodologies, modeling, and tools for facilitating the commercial development of space and supporting diverse exploration and scientific missions. Also, the workshop addressed important topic areas including revolutionary space systems requiring investments in innovative advanced technologies; achieving transformational space operations through the insertion of new technologies; revolutionary science in space through advanced systems and new technologies enabling experiments to go anytime to any location; and, innovative and ambitious concepts and approaches essential for promoting advancements in space transportation. Details concerning the workshop process, structure, and results are contained in the ensuing report.

Accelerating Time Integration for the Shallow Water Equations on the Sphere Using GPUs

DOE PAGES

Archibald, R.; Evans, K. J.; Salinger, A.

2015-06-01

The push towards larger and larger computational platforms has made it possible for climate simulations to resolve climate dynamics across multiple spatial and temporal scales. This direction in climate simulation has created a strong need to develop scalable timestepping methods capable of accelerating throughput on high performance computing. This study details the recent advances in the implementation of implicit time stepping of the spectral element dynamical core within the United States Department of Energy (DOE) Accelerated Climate Model for Energy (ACME) on graphical processing units (GPU) based machines. We demonstrate how solvers in the Trilinos project are interfaced with ACMEmore » and GPU kernels to increase computational speed of the residual calculations in the implicit time stepping method for the atmosphere dynamics. We demonstrate the optimization gains and data structure reorganization that facilitates the performance improvements.« less

Development of a GC/Quadrupole-Orbitrap Mass Spectrometer, Part I: Design and Characterization

PubMed Central

2015-01-01

Identification of unknown compounds is of critical importance in GC/MS applications (metabolomics, environmental toxin identification, sports doping, petroleomics, and biofuel analysis, among many others) and remains a technological challenge. Derivation of elemental composition is the first step to determining the identity of an unknown compound by MS, for which high accuracy mass and isotopomer distribution measurements are critical. Here, we report on the development of a dedicated, applications-grade GC/MS employing an Orbitrap mass analyzer, the GC/Quadrupole-Orbitrap. Built from the basis of the benchtop Orbitrap LC/MS, the GC/Quadrupole-Orbitrap maintains the performance characteristics of the Orbitrap, enables quadrupole-based isolation for sensitive analyte detection, and includes numerous analysis modalities to facilitate structural elucidation. We detail the design and construction of the instrument, discuss its key figures-of-merit, and demonstrate its performance for the characterization of unknown compounds and environmental toxins. PMID:25208235

Suborbital Science Program: Dryden Flight Research Center

NASA Technical Reports Server (NTRS)

DelFrate, John

2008-01-01

This viewgraph presentation reviews the suborbital science program at NASA Dryden Flight Research Center. The Program Objectives are given in various areas: (1) Satellite Calibration and Validation (Cal/val)--Provide methods to perform the cal/val requirements for Earth Observing System satellites; (2) New Sensor Development -- Provide methods to reduce risk for new sensor concepts and algorithm development prior to committing sensors to operations; (3) Process Studies -- Facilitate the acquisition of high spatial/temporal resolution focused measurements that are required to understand small atmospheric and surface structures which generate powerful Earth system effects; and (4) Airborne Networking -- Develop disruption-tolerant networking to enable integrated multiple scale measurements of critical environmental features. Dryden supports the NASA Airborne Science Program and the nation in several elements: ER-2, G-3, DC-8, Ikhana (Predator B) & Global Hawk and Reveal. These are reviewed in detail in the presentation.

An experience of group work with parents of children and adolescents with gender identity disorder.

PubMed

Di Ceglie, Domenico; Thümmel, Elizabeth Coates

2006-07-01

This article gives an account of an experience of group work with parents and carers who had children or adolescents with gender identity disorder (GID). The history of this intervention within the context of a service for children with gender identity problems is outlined. The limited literature on the subject is reviewed. Group meetings were held monthly for 6 months, facilitated by two therapists (the authors). Selection criteria for group participants, the aims of the group and the methodology for achieving those aims are described. Some information about the group's composition is provided. The structure and content of the group sessions are outlined together with details of some group interactions. Finally, we present the results of an evaluation of the intervention through feedback questionnaires and discuss the value for the children and young people of running such groups.

Solution NMR Spectroscopy for the Study of Enzyme Allostery

PubMed Central

Lisi, George P.; Loria, J. Patrick

2016-01-01

Allostery is a ubiquitous biological regulatory process in which distant binding sites within a protein or enzyme are functionally and thermodynamically coupled. Allosteric interactions play essential roles in many enzymological mechanisms, often facilitating formation of enzyme-substrate complexes and/or product release. Thus, elucidating the forces that drive allostery is critical to understanding the complex transformations of biomolecules. Currently, a number of models exist to describe allosteric behavior, taking into account energetics as well as conformational rearrangements and fluctuations. In the following review, we discuss the use of solution NMR techniques designed to probe allosteric mechanisms in enzymes. NMR spectroscopy is unequaled in its ability to detect structural and dynamical changes in biomolecules, and the case studies presented herein demonstrate the range of insights to be gained from this valuable method. We also provide a detailed technical discussion of several specialized NMR experiments that are ideally suited for the study of enzymatic allostery. PMID:26734986

Cell and molecular mechanics of biological materials

NASA Astrophysics Data System (ADS)

Bao, G.; Suresh, S.

2003-11-01

Living cells can sense mechanical forces and convert them into biological responses. Similarly, biological and biochemical signals are known to influence the abilities of cells to sense, generate and bear mechanical forces. Studies into the mechanics of single cells, subcellular components and biological molecules have rapidly evolved during the past decade with significant implications for biotechnology and human health. This progress has been facilitated by new capabilities for measuring forces and displacements with piconewton and nanometre resolutions, respectively, and by improvements in bio-imaging. Details of mechanical, chemical and biological interactions in cells remain elusive. However, the mechanical deformation of proteins and nucleic acids may provide key insights for understanding the changes in cellular structure, response and function under force, and offer new opportunities for the diagnosis and treatment of disease. This review discusses some basic features of the deformation of single cells and biomolecules, and examines opportunities for further research.

Anharmonic Vibrational Spectroscopy on Metal Transition Complexes

NASA Astrophysics Data System (ADS)

Latouche, Camille; Bloino, Julien; Barone, Vincenzo

2014-06-01

Advances in hardware performance and the availability of efficient and reliable computational models have made possible the application of computational spectroscopy to ever larger molecular systems. The systematic interpretation of experimental data and the full characterization of complex molecules can then be facilitated. Focusing on vibrational spectroscopy, several approaches have been proposed to simulate spectra beyond the double harmonic approximation, so that more details become available. However, a routine use of such tools requires the preliminary definition of a valid protocol with the most appropriate combination of electronic structure and nuclear calculation models. Several benchmark of anharmonic calculations frequency have been realized on organic molecules. Nevertheless, benchmarks of organometallics or inorganic metal complexes at this level are strongly lacking despite the interest of these systems due to their strong emission and vibrational properties. Herein we report the benchmark study realized with anharmonic calculations on simple metal complexes, along with some pilot applications on systems of direct technological or biological interest.

Using Cross-Sectional Imaging to Convey Organ Relationships: An Integrated Learning Environment for Students of Gross Anatomy

PubMed Central

Forman, Bruce H.; Eccles, Randy; Piggins, Judith; Raila, Wayne; Estey, Greg; Barnett, G. Octo

1990-01-01

We have developed a visually oriented, computer-controlled learning environment designed for use by students of gross anatomy. The goals of this module are to reinforce the concepts of organ relationships and topography by using computed axial tomographic (CAT) images accessed from a videodisc integrated with color graphics and to introduce students to cross-sectional radiographic anatomy. We chose to build the program around CAT scan images because they not only provide excellent structural detail but also offer an anatomic orientation (transverse) that complements that used in the dissection laboratory (basically a layer-by-layer, anterior-to-posterior, or coronal approach). Our system, built using a Microsoft Windows-386 based authoring environment which we designed and implemented, integrates text, video images, and graphics into a single screen display. The program allows both user browsing of information, facilitated by hypertext links, and didactic sessions including mini-quizzes for self-assessment.

JPL space robotics: Present accomplishments and future thrusts

NASA Technical Reports Server (NTRS)

Weisbin, C. R.; Hayati, S. A.; Rodriguez, G.

1994-01-01

Complex missions require routine and unscheduled inspection for safe operation. The purpose of research in this task is to facilitate structural inspection of the planned Space Station while mitigating the need for extravehicular activity (EVA), and giving the operator supervisory control over detailed and somewhat mundane, but important tasks. The telerobotic system enables inspection relative to a given reference (e.g., the status of the facility at the time of the last inspection) and alerts the operator to potential anomalies for verification and action. There are two primary objectives of this project: (1) To develop technologies that enable well-integrated NASA ground-to-orbit telerobotics operations, and (2) to develop a prototype common architecture workstation which implements these capabilities for other NASA technology projects and planned NASA flight applications. This task develops and supports three telerobot control modes which are applicable to time delay operation: Preview teleoperation, teleprogramming, and supervised autonomy.

Topical Review: Unique Contributions of Magnetic Resonance Imaging to Pediatric Psychology Research

PubMed Central

Duraccio, Kara M.; Carbine, Kaylie M.; Kirwan, C. Brock

2016-01-01

Objective This review aims to provide a brief introduction of the utility of magnetic resonance imaging (MRI) methods in pediatric psychology research, describe several exemplar studies that highlight the unique benefits of MRI techniques for pediatric psychology research, and detail methods for addressing several challenges inherent to pediatric MRI research. Methods Literature review. Results Numerous useful applications of MRI research in pediatric psychology have been illustrated in published research. MRI methods yield information that cannot be obtained using neuropsychological or behavioral measures. Conclusions Using MRI in pediatric psychology research may facilitate examination of neural structures and processes that underlie health behaviors. Challenges inherent to conducting MRI research with pediatric research participants (e.g., head movement) may be addressed using evidence-based strategies. We encourage pediatric psychology researchers to consider adopting MRI techniques to answer research questions relevant to pediatric health and illness. PMID:26141118

Nonlinear network model analysis of vibrational energy transfer and localisation in the Fenna-Matthews-Olson complex

NASA Astrophysics Data System (ADS)

Morgan, Sarah E.; Cole, Daniel J.; Chin, Alex W.

2016-11-01

Collective protein modes are expected to be important for facilitating energy transfer in the Fenna-Matthews-Olson (FMO) complex of photosynthetic green sulphur bacteria, however to date little work has focussed on the microscopic details of these vibrations. The nonlinear network model (NNM) provides a computationally inexpensive approach to studying vibrational modes at the microscopic level in large protein structures, whilst incorporating anharmonicity in the inter-residue interactions which can influence protein dynamics. We apply the NNM to the entire trimeric FMO complex and find evidence for the existence of nonlinear discrete breather modes. These modes tend to transfer energy to the highly connected core pigments, potentially opening up alternative excitation energy transfer routes through their influence on pigment properties. Incorporating localised modes based on these discrete breathers in the optical spectra calculations for FMO using ab initio site energies and excitonic couplings can substantially improve their agreement with experimental results.

Combining atomic force and fluorescence microscopy for analysis of quantum-dot labeled protein–DNA complexes

PubMed Central

Ebenstein, Yuval; Gassman, Natalie; Kim, Soohong; Weiss, Shimon

2011-01-01

Atomic force microscopy (AFM) and fluorescence microscopy are widely used for the study of protein-DNA interactions. While AFM excels in its ability to elucidate structural detail and spatial arrangement, it lacks the ability to distinguish between similarly sized objects in a complex system. This information is readily accessible to optical imaging techniques via site-specific fluorescent labels, which enable the direct detection and identification of multiple components simultaneously. Here, we show how the utilization of semiconductor quantum dots (QDs), serving as contrast agents for both AFM topography and fluorescence imaging, facilitates the combination of both imaging techniques, and with the addition of a flow based DNA extension method for sample deposition, results in a powerful tool for the study of protein-DNA complexes. We demonstrate the inherent advantages of this novel combination of techniques by imaging individual RNA polymerases (RNAP) on T7 genomic DNA. PMID:19452448

Plant Virus Cell-to-Cell Movement Is Not Dependent on the Transmembrane Disposition of Its Movement Protein▿ †

PubMed Central

Martínez-Gil, Luis; Sánchez-Navarro, Jesús A.; Cruz, Antonio; Pallás, Vicente; Pérez-Gil, Jesús; Mingarro, Ismael

2009-01-01

The cell-to-cell transport of plant viruses depends on one or more virus-encoded movement proteins (MPs). Some MPs are integral membrane proteins that interact with the membrane of the endoplasmic reticulum, but a detailed understanding of the interaction between MPs and biological membranes has been lacking. The cell-to-cell movement of the Prunus necrotic ringspot virus (PNRSV) is facilitated by a single MP of the 30K superfamily. Here, using a myriad of biochemical and biophysical approaches, we show that the PNRSV MP contains only one hydrophobic region (HR) that interacts with the membrane interface, as opposed to being a transmembrane protein. We also show that a proline residue located in the middle of the HR constrains the structural conformation of this region at the membrane interface, and its replacement precludes virus movement. PMID:19321624

Plant virus cell-to-cell movement is not dependent on the transmembrane disposition of its movement protein.

PubMed

Martínez-Gil, Luis; Sánchez-Navarro, Jesús A; Cruz, Antonio; Pallás, Vicente; Pérez-Gil, Jesús; Mingarro, Ismael

2009-06-01

The cell-to-cell transport of plant viruses depends on one or more virus-encoded movement proteins (MPs). Some MPs are integral membrane proteins that interact with the membrane of the endoplasmic reticulum, but a detailed understanding of the interaction between MPs and biological membranes has been lacking. The cell-to-cell movement of the Prunus necrotic ringspot virus (PNRSV) is facilitated by a single MP of the 30K superfamily. Here, using a myriad of biochemical and biophysical approaches, we show that the PNRSV MP contains only one hydrophobic region (HR) that interacts with the membrane interface, as opposed to being a transmembrane protein. We also show that a proline residue located in the middle of the HR constrains the structural conformation of this region at the membrane interface, and its replacement precludes virus movement.

Exploring the Use of a Social Network to Facilitate and Integrate Long-Term Interprofessional Educational Experiences

ERIC Educational Resources Information Center

Pittenger, Amy L.

2011-01-01

The purpose of this study was to evaluate the feasibility and effectiveness of implementing interprofessional education to students from six health professional programs through use of an online social networking platform. Specifically, three pedagogical models (Minimally Structured, Facilitated, Highly Structured) were evaluated for impact on…

Arguments, Contradictions, Resistances, and Conceptual Change in Students' Understanding of Atomic Structure.

ERIC Educational Resources Information Center

Niaz, Mansoor; Aguilera, Damarys; Maza, Arelys; Liendo, Gustavo

2002-01-01

Reports on a study aimed at facilitating freshman general chemistry students' understanding of atomic structure based on the work of Thomson, Rutherford, and Bohr. Hypothesizes that classroom discussions based on arguments/counterarguments of the heuristic principles on which these scientists based their atomic models can facilitate students'…

Analysis of the process of representing clinical statements for decision-support applications: a comparison of openEHR archetypes and HL7 virtual medical record.

PubMed

González-Ferrer, A; Peleg, M; Marcos, M; Maldonado, J A

2016-07-01

Delivering patient-specific decision-support based on computer-interpretable guidelines (CIGs) requires mapping CIG clinical statements (data items, clinical recommendations) into patients' data. This is most effectively done via intermediate data schemas, which enable querying the data according to the semantics of a shared standard intermediate schema. This study aims to evaluate the use of HL7 virtual medical record (vMR) and openEHR archetypes as intermediate schemas for capturing clinical statements from CIGs that are mappable to electronic health records (EHRs) containing patient data and patient-specific recommendations. Using qualitative research methods, we analyzed the encoding of ten representative clinical statements taken from two CIGs used in real decision-support systems into two health information models (openEHR archetypes and HL7 vMR instances) by four experienced informaticians. Discussion among the modelers about each case study example greatly increased our understanding of the capabilities of these standards, which we share in this educational paper. Differing in content and structure, the openEHR archetypes were found to contain a greater level of representational detail and structure while the vMR representations took fewer steps to complete. The use of openEHR in the encoding of CIG clinical statements could potentially facilitate applications other than decision-support, including intelligent data analysis and integration of additional properties of data items from existing EHRs. On the other hand, due to their smaller size and fewer details, the use of vMR potentially supports quicker mapping of EHR data into clinical statements.

High incidence of echocardiographic abnormalities of the interatrial septum in patients undergoing ablation for atrial fibrillation.

PubMed

Schernthaner, Christiana; Danmayr, Franz; Daburger, Apollonia; Eichinger, Jörg; Hammerer, Matthias; Strohmer, Bernhard

2013-04-01

Atrial fibrosis or fatty deposition is known to increase the propensity for the development of atrial fibrillation (AF). Apart from the pulmonic veins, the interatrial septum (IAS) might play a role in the maintenance of AF. In contrast to left atrial anatomy and adjacent veins, the IAS cannot be visualized in detail with computed tomography. Thus, preprocedural transesophageal echocardiography (TEE) may provide important morphologic information beyond exclusion from atrial thrombi. The study comprised 108 consecutive patients (mean age 60 ± 11 years; 98 men). AF was paroxysmal in 91 (84%) and persistent in 17 (16%) patients. We investigated the morphological characteristics of the IAS by TEE in patients who underwent radiofrequency ablation of AF. The IAS was structurally abnormal in 46 (43%) patients, showing the following echocardiograhic findings: atrial septal hypermobility or aneurysm (n = 27) associated with a patent foramen ovale (PFO) (n = 11) or with a small atrial septal defect (ASD) (n = 2), a septal flap associated with a PFO or an ASD (n = 8), and an abnormally thickened IAS (n = 12). A thrombus in the left atrial appendage was discovered in only 2 (2%) patients. A structurally abnormal IAS was diagnosed in nearly half of the patients undergoing ablation therapy for AF. The information obtained by TEE is mandatory to exclude left atrial thrombi prior the ablation procedure. Moreover, detailed knowledge of morphologic characteristics of the IAS facilitates an optimized and safe performance of the transseptal puncture using long sheaths with large diameters. © 2012, Wiley Periodicals, Inc.

Folding domain B of protein A on a dynamically partitioned free energy landscape.

PubMed

Nelson, Erik D; Grishin, Nick V

2008-02-05

The B domain of staphylococcal protein A (BdpA) is a small helical protein that has been studied intensively in kinetics experiments and detailed computer simulations that include explicit water. The simulations indicate that BdpA needs to reorganize in crossing the transition barrier to facilitate folding its C-terminal helix (H3) onto the nucleus formed from helices H1 and H2. This process suggests frustration between two partially ordered forms of the protein, but recent varphi value measurements indicate that the transition structure is relatively constant over a broad range of temperatures. Here we develop a simplistic model to investigate the folding transition in which properties of the free energy landscape can be quantitatively compared with experimental data. The model is a continuation of the Muñoz-Eaton model to include the intermittency of contacts between structured parts of the protein, and the results compare variations in the landscape with denaturant and temperature to varphi value measurements and chevron plots of the kinetic rates. The topography of the model landscape (in particular, the feature of frustration) is consistent with detailed simulations even though variations in the varphi values are close to measured values. The transition barrier is smaller than indicated by the chevron data, but it agrees in order of magnitude with a similar alpha-carbon type of model. Discrepancies with the chevron plots are investigated from the point of view of solvent effects, and an approach is suggested to account for solvent participation in the model.

Planning and design of studies for river-quality assessment in the Truckee and Carson River basins, California and Nevada

USGS Publications Warehouse

Nowlin, Jon O.; Brown, W.M.; Smith, L.H.; Hoffman, R.J.

1980-01-01

The objectives of the Geological Survey 's river-quality assessment in the Truckee and Carson River basins in California and Nevada are to identify the significant resource management problems; to develop techniques to assess the problems; and to effectively communicate results to responsible managers. Six major elements of the assessment to be completed by October 1981 are (1) a detailing of the legal, institutional, and structural development of water resources in the basins and the current problems and conflicts; (2) a compilation and synthesis of the physical hydrology of the basins; (3) development of a special workshop approach to involve local management in the direction and results of the study; (4) development of a comprehensive streamflow model emcompassing both basins to provide a quantitative hydrologic framework for water-quality analysis; (5) development of a water-quality transport model for selected constituents and characteristics on selected reaches of the Truckee River; and (6) a detailed examination of selected fish habitats for specified reaches of the Truckee River. Progress will be periodically reported in reports, maps, computer data files, mathematical models, a bibliography, and public presentations. In building a basic framework to develop techniques, the basins were viewed as a single hydrologic unit because of interconnecting diversion structures. The framework comprises 13 hydrographic subunits to facilitate modeling and sampling. Several significant issues beyond the scope of the assessment were considered as supplementary proposals; water-quality loadings in Truckee and Carson Rivers, urban runoff in Reno and management alternatives, and a model of limnological processes in Lahontan Reservoir. (USGS)

[Connecting biobanks of large European cohorts (EU Project BBMRI-LPC)].

PubMed

Kuhn, Klaus A; Bild, Raffael; Anton, Gabriele; Schuffenhauer, Simone; Wichmann, H-Erich

2016-03-01

In addition to the Biobanking and BioMolecular resources Research Initiative (BBMRI), which is establishing a European research infrastructure for biobanks, a network for large European prospective cohorts (LPC) is being built to facilitate transnational research into important groups of diseases and health care. One instrument for this is the database "LPC Catalogue," which supports access to the biomaterials of the participating cohorts. To present the LPC Catalogue as a relevant tool for connecting European biobanks. In addition, the LPC Catalogue has been extended to establish compatibility with existing Minimum Information About Biobank data Sharing (MIABIS) and to allow for more detailed search requests. This article describes the LPC Catalogue, its organizational and technical structure, and the aforementioned extensions. The LPC Catalogue provides a structured overview of the participating LPCs. It offers various retrieval possibilities and a search function. To support more detailed search requests, a new module has been developed, called a "data cube". The provision of data by the cohorts is being supported by a "connector" component. The LPC Catalogue contains data on 22 cohorts and more than 3.8 million biosamples. At present, data on the biosamples of three cohorts have been acquired for the "cube," which is continuously being expanded. In the BBMRI-LPC, tendering for scientific projects using the data and samples of the participating cohorts is currently being carried out. In this context, several proposals have already been approved. The LPC Catalogue is supporting transnational access to biosamples. A comparison with existing solutions illustrates the relevance of its functionality.

Testing and injury potential analysis of rollovers with narrow object impacts.

PubMed

Meyer, Steven E; Forrest, Stephen; Herbst, Brian; Hayden, Joshua; Orton, Tia; Sances, Anthony; Kumaresan, Srirangam

2004-01-01

Recent statistics highlight the significant risk of serious and fatal injuries to occupants involved in rollover collisions due to excessive roof crush. The government has reported that in 2002. Sports Utility Vehicle rollover related fatalities increased by 14% to more than 2400 annually. 61% of all SUV fatalities included rollovers [1]. Rollover crashes rely primarily upon the roof structures to maintain occupant survival space. Frequently these crashes occur off the travel lanes of the roadway and, therefore, can include impacts with various types of narrow objects such as light poles, utility poles and/or trees. A test device and methodology is presented which facilitates dynamic, repeatable rollover impact evaluation of complete vehicle roof structures with such narrow objects. These tests allow for the incorporation of Anthropomorphic Test Dummies (ATDs) which can be instrumented to measure accelerations, forces and moments to evaluate injury potential. High-speed video permits for detailed analysis of occupant kinematics and evaluation of injury causation. Criteria such as restraint performance, injury potential, survival space and the effect of roof crush associated with various types of design alternatives, countermeasures and impact circumstances can also be evaluated. In addition to presentation of the methodology, two representative vehicle crash tests are also reported. Results indicated that the reinforced roof structure significantly reduced the roof deformation compared to the production roof structure.

Differentiation of isomeric N-glycan structures by normal-phase liquid chromatography-MALDI-TOF/TOF tandem mass spectrometry.

PubMed

Maslen, Sarah; Sadowski, Pawel; Adam, Alex; Lilley, Kathryn; Stephens, Elaine

2006-12-15

The detailed characterization of protein N-glycosylation is very demanding given the many different glycoforms and structural isomers that can exist on glycoproteins. Here we report a fast and sensitive method for the extensive structure elucidation of reducing-end labeled N-glycan mixtures using a combination of capillary normal-phase HPLC coupled off-line to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and TOF/TOF-MS/MS. Using this method, isobaric N-glycans released from honey bee phospholipase A2 and Arabidopsis thaliana glycoproteins were separated by normal-phase chromatography and subsequently identified by key fragment ions in the MALDI-TOF/TOF tandem mass spectra. In addition, linkage and branching information were provided by abundant cross-ring and "elimination" fragment ions in the MALDI-CID spectra that gave extensive structural information. Furthermore, the fragmentation characteristics of N-glycans reductively aminated with 2-aminobenzoic acid and 2-aminobenzamide were compared. The identification of N-glycans containing 3-linked core fucose was facilitated by distinctive ions present only in the MALDI-CID spectra of 2-aminobenzoic acid-labeled oligosaccharides. To our knowledge, this is the first MS/MS-based technique that allows confident identification of N-glycans containing 3-linked core fucose, which is a major allergenic determinant on insect and plant glycoproteins.

Are gay communities dying or just in transition? Results from an international consultation examining possible structural change in gay communities.

PubMed

Simon Rosser, B R; West, William; Weinmeyer, Richard

2008-05-01

This study sought to identify how urban gay communities are undergoing structural change, reasons for that change, and implications for HIV prevention planning. Key informants (N=29) at the AIDS Impact Conference from 17 cities in 14 countries completed surveys and participated in a facilitated structured dialog about if gay communities are changing, and if so, how they are changing. In all cities, the virtual gay community was identified as currently larger than the offline physical community. Most cities identified that while the gay population in their cities appeared stable or growing, the gay community appeared in decline. Measures included greater integration of heterosexuals into historically gay-identified neighborhoods and movement of gay persons into suburbs, decreased number of gay bars/clubs, less attendance at gay events, less volunteerism in gay or HIV/AIDS organizations, and the overall declining visibility of gay communities. Participants attributed structural change to multiple factors including gay neighborhood gentrification, achievement of civil rights, less discrimination, a vibrant virtual community, and changes in drug use. Consistent with social assimilation, gay infrastructure, visibility, and community identification appears to be decreasing across cities. HIV prevention planning, interventions, treatment services, and policies need to be re-conceptualized for MSM in the future. Four recommendations for future HIV prevention and research are detailed.

How Staphylococcus aureus biofilms develop their characteristic structure

PubMed Central

Periasamy, Saravanan; Joo, Hwang-Soo; Duong, Anthony C.; Bach, Thanh-Huy L.; Tan, Vee Y.; Chatterjee, Som S.; Cheung, Gordon Y. C.; Otto, Michael

2012-01-01

Biofilms cause significant problems in the environment and during the treatment of infections. However, the molecular mechanisms underlying biofilm formation are poorly understood. There is a particular lack of knowledge about biofilm maturation processes, such as biofilm structuring and detachment, which are deemed crucial for the maintenance of biofilm viability and the dissemination of cells from a biofilm. Here, we identify the phenol-soluble modulin (PSM) surfactant peptides as key biofilm structuring factors in the premier biofilm-forming pathogen Staphylococcus aureus. We provide evidence that all known PSM classes participate in structuring and detachment processes. Specifically, absence of PSMs in isogenic S. aureus psm deletion mutants led to strongly impaired formation of biofilm channels, abolishment of the characteristic waves of biofilm detachment and regrowth, and loss of control of biofilm expansion. In contrast, induced expression of psm loci in preformed biofilms promoted those processes. Furthermore, PSMs facilitated dissemination from an infected catheter in a mouse model of biofilm-associated infection. Moreover, formation of the biofilm structure was linked to strongly variable, quorum sensing-controlled PSM expression in biofilm microenvironments, whereas overall PSM production remained constant to ascertain biofilm homeostasis. Our study describes a mechanism of biofilm structuring in molecular detail, and the general principle (i.e., quorum-sensing controlled expression of surfactants) seems to be conserved in several bacteria, despite the divergence of the respective biofilm-structuring surfactants. These findings provide a deeper understanding of biofilm development processes, which represents an important basis for strategies to interfere with biofilm formation in the environment and human disease. PMID:22232686

Psychological Perspectives on Interrogation.

PubMed

Vrij, Aldert; Meissner, Christian A; Fisher, Ronald P; Kassin, Saul M; Morgan, Charles A; Kleinman, Steven M

2017-11-01

Proponents of "enhanced interrogation techniques" in the United States have claimed that such methods are necessary for obtaining information from uncooperative terrorism subjects. In the present article, we offer an informed, academic perspective on such claims. Psychological theory and research shows that harsh interrogation methods are ineffective. First, they are likely to increase resistance by the subject rather than facilitate cooperation. Second, the threatening and adversarial nature of harsh interrogation is often inimical to the goal of facilitating the retrieval of information from memory and therefore reduces the likelihood that a subject will provide reports that are extensive, detailed, and accurate. Third, harsh interrogation methods make lie detection difficult. Analyzing speech content and eliciting verifiable details are the most reliable cues to assessing credibility; however, to elicit such cues subjects must be encouraged to provide extensive narratives, something that does not occur in harsh interrogations. Evidence is accumulating for the effectiveness of rapport-based information-gathering approaches as an alternative to harsh interrogations. Such approaches promote cooperation, enhance recall of relevant and reliable information, and facilitate assessments of credibility. Given the available evidence that torture is ineffective, why might some laypersons, policymakers, and interrogation personnel support the use of torture? We conclude our review by offering a psychological perspective on this important question.

Positive Psychology and Career Development

ERIC Educational Resources Information Center

Aulthouse, Michelle; Kolbert, Jered B.; Bundick, Matthew J.; Crothers, Laura M.

2017-01-01

The article details how school counselors can use principles of positive psychology to promote students' career development by facilitating students' pursuit of purpose and meaning. Specifically, the publication identifies how school counselors can actively employ with their students five constructs of positive psychology--namely strengths,…

Tissue Regeneration: A Silk Road.

PubMed

Jao, Dave; Mou, Xiaoyang; Hu, Xiao

2016-08-05

Silk proteins are natural biopolymers that have extensive structural possibilities for chemical and mechanical modifications to facilitate novel properties, functions, and applications in the biomedical field. The versatile processability of silk fibroins (SF) into different forms such as gels, films, foams, membranes, scaffolds, and nanofibers makes it appealing in a variety of applications that require mechanically superior, biocompatible, biodegradable, and functionalizable biomaterials. There is no doubt that nature is the world's best biological engineer, with simple, exquisite but powerful designs that have inspired novel technologies. By understanding the surface interaction of silk materials with living cells, unique characteristics can be implemented through structural modifications, such as controllable wettability, high-strength adhesiveness, and reflectivity properties, suggesting its potential suitability for surgical, optical, and other biomedical applications. All of the interesting features of SF, such as tunable biodegradation, anti-bacterial properties, and mechanical properties combined with potential self-healing modifications, make it ideal for future tissue engineering applications. In this review, we first demonstrate the current understanding of the structures and mechanical properties of SF and the various functionalizations of SF matrices through chemical and physical manipulations. Then the diverse applications of SF architectures and scaffolds for different regenerative medicine will be discussed in detail, including their current applications in bone, eye, nerve, skin, tendon, ligament, and cartilage regeneration.

IRaPPA: information retrieval based integration of biophysical models for protein assembly selection.

PubMed

Moal, Iain H; Barradas-Bautista, Didier; Jiménez-García, Brian; Torchala, Mieczyslaw; van der Velde, Arjan; Vreven, Thom; Weng, Zhiping; Bates, Paul A; Fernández-Recio, Juan

2017-06-15

In order to function, proteins frequently bind to one another and form 3D assemblies. Knowledge of the atomic details of these structures helps our understanding of how proteins work together, how mutations can lead to disease, and facilitates the designing of drugs which prevent or mimic the interaction. Atomic modeling of protein-protein interactions requires the selection of near-native structures from a set of docked poses based on their calculable properties. By considering this as an information retrieval problem, we have adapted methods developed for Internet search ranking and electoral voting into IRaPPA, a pipeline integrating biophysical properties. The approach enhances the identification of near-native structures when applied to four docking methods, resulting in a near-native appearing in the top 10 solutions for up to 50% of complexes benchmarked, and up to 70% in the top 100. IRaPPA has been implemented in the SwarmDock server ( http://bmm.crick.ac.uk/∼SwarmDock/ ), pyDock server ( http://life.bsc.es/pid/pydockrescoring/ ) and ZDOCK server ( http://zdock.umassmed.edu/ ), with code available on request. moal@ebi.ac.uk. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Evolutionary tabu search strategies for the simultaneous registration of multiple atomic structures in cryo-EM reconstructions.

PubMed

Rusu, Mirabela; Birmanns, Stefan

2010-04-01

A structural characterization of multi-component cellular assemblies is essential to explain the mechanisms governing biological function. Macromolecular architectures may be revealed by integrating information collected from various biophysical sources - for instance, by interpreting low-resolution electron cryomicroscopy reconstructions in relation to the crystal structures of the constituent fragments. A simultaneous registration of multiple components is beneficial when building atomic models as it introduces additional spatial constraints to facilitate the native placement inside the map. The high-dimensional nature of such a search problem prevents the exhaustive exploration of all possible solutions. Here we introduce a novel method based on genetic algorithms, for the efficient exploration of the multi-body registration search space. The classic scheme of a genetic algorithm was enhanced with new genetic operations, tabu search and parallel computing strategies and validated on a benchmark of synthetic and experimental cryo-EM datasets. Even at a low level of detail, for example 35-40 A, the technique successfully registered multiple component biomolecules, measuring accuracies within one order of magnitude of the nominal resolutions of the maps. The algorithm was implemented using the Sculptor molecular modeling framework, which also provides a user-friendly graphical interface and enables an instantaneous, visual exploration of intermediate solutions. (c) 2009 Elsevier Inc. All rights reserved.

A chimeric prokaryotic pentameric ligand–gated channel reveals distinct pathways of activation

DOE PAGES

Schmandt, Nicolaus; Velisetty, Phanindra; Chalamalasetti, Sreevatsa V.; ...

2015-09-28

Recent high resolution structures of several pentameric ligand–gated ion channels have provided unprecedented details of their molecular architecture. However, the conformational dynamics and structural rearrangements that underlie gating and allosteric modulation remain poorly understood. We used a combination of electrophysiology, double electron–electron resonance (DEER) spectroscopy, and x-ray crystallography to investigate activation mechanisms in a novel functional chimera with the extracellular domain (ECD) of amine-gated Erwinia chrysanthemi ligand–gated ion channel, which is activated by primary amines, and the transmembrane domain of Gloeobacter violaceus ligand–gated ion channel, which is activated by protons. We found that the chimera was independently gated by primarymore » amines and by protons. The crystal structure of the chimera in its resting state, at pH 7.0 and in the absence of primary amines, revealed a closed-pore conformation and an ECD that is twisted with respect to the transmembrane region. Amine- and pH-induced conformational changes measured by DEER spectroscopy showed that the chimera exhibits a dual mode of gating that preserves the distinct conformational changes of the parent channels. Collectively, our findings shed light on both conserved and divergent features of gating mechanisms in this class of channels, and will facilitate the design of better allosteric modulators.« less

Regional variations in the density and arrangement of elastic fibres in the anulus fibrosus of the human lumbar disc

PubMed Central

Smith, Lachlan J; Fazzalari, Nicola L

2006-01-01

Elastic fibres are critical components of the extracellular matrix in dynamic biological structures that undergo extension and recoil. Their presence has been demonstrated in the anulus fibrosus of the human lumbar intervertebral disc; however, a detailed regional analysis of their density and arrangement has not been undertaken, limiting our understanding of their structural and functional roles. In this investigation we have quantitatively described regional variations in elastic fibre density in the anulus fibrosus of the human L3–L4 intervertebral disc using histochemistry and light microscopy. Additionally, a multiplanar comparison of patterns of elastic fibre distribution in the intralamellar and interlamellar zones was undertaken. Novel imaging techniques were developed to facilitate the visualization of elastic fibres otherwise masked by dense surrounding matrix. Elastic fibre density was found to be significantly higher in the lamellae of the posterolateral region of the anulus than the anterolateral, and significantly higher in the outer regions than the inner, suggesting that elastic fibre density in each region of the anulus is commensurate with the magnitude of the tensile deformations experienced in bending and torsion. Elastic fibre arrangments in intralamellar and interlamellar zones were shown to be architecturally distinct, suggesting that they perform multiple functional roles within the anulus matrix structural hierarchy. PMID:16928204

A New Publicly Available Chemical Query Language, CSRML ...

EPA Pesticide Factsheets

A new XML-based query language, CSRML, has been developed for representing chemical substructures, molecules, reaction rules, and reactions. CSRML queries are capable of integrating additional forms of information beyond the simple substructure (e.g., SMARTS) or reaction transformation (e.g., SMIRKS, reaction SMILES) queries currently in use. Chemotypes, a term used to represent advanced CSRML queries for repeated application can be encoded not only with connectivity and topology, but also with properties of atoms, bonds, electronic systems, or molecules. The CSRML language has been developed in parallel with a public set of chemotypes, i.e., the ToxPrint chemotypes, which are designed to provide excellent coverage of environmental, regulatory and commercial use chemical space, as well as to represent features and frameworks believed to be especially relevant to toxicity concerns. A software application, ChemoTyper, has also been developed and made publicly available to enable chemotype searching and fingerprinting against a target structure set. The public ChemoTyper houses the ToxPrint chemotype CSRML dictionary, as well as reference implementation so that the query specifications may be adopted by other chemical structure knowledge systems. The full specifications of the XML standard used in CSRML-based chemotypes are publicly available to facilitate and encourage the exchange of structural knowledge. Paper details specifications for a new XML-based query lan

Site characterization at Groningen gas field area through joint surface-borehole H/V analysis

NASA Astrophysics Data System (ADS)

Spica, Zack J.; Perton, Mathieu; Nakata, Nori; Liu, Xin; Beroza, Gregory C.

2018-01-01

A new interpretation of the horizontal to vertical (H/V) spectral ratio in terms of the Diffuse Field Assumption (DFA) has fuelled a resurgence of interest in that approach. The DFA links H/V measurements to Green's function retrieval through autocorrelation of the ambient seismic field. This naturally allows for estimation of layered velocity structure. In this contribution, we further explore the potential of H/V analysis. Our study is facilitated by a distributed array of surface and co-located borehole stations deployed at multiple depths, and by detailed prior information on velocity structure that is available due to development of the Groningen gas field. We use the vertical distribution of H/V spectra recorded at discrete depths inside boreholes to obtain shear wave velocity models of the shallow subsurface. We combine both joint H/V inversion and borehole interferometry to reduce the non-uniqueness of the problem and to allow faster convergence towards a reliable velocity model. The good agreement between our results and velocity models from an independent study validates the methodology, demonstrates the power of the method, but more importantly provides further constraints on the shallow velocity structure, which is an essential component of integrated hazard assessment in the area.

Crustal structure of Shatsky Rise from joint refraction and reflection seismic tomography

NASA Astrophysics Data System (ADS)

Korenaga, J.; Sager, W. W.

2011-12-01

Shatsky Rise in the western Pacific is one of a few gigantic oceanic plateaus in the world, with a surface area of ˜ 4.8 ± 105~km2 (about the same size as California). In contrast to other large oceanic plateaus formed during the Cretaceous Quite Period, Shatsky Rise formed during the frequent reversals of magnetic polarity, allowing its tectonic environment to be resolved in detail. It was formed at a rapidly spreading ridge-ridge-ridge triple junction, so the effect of lithospheric lid on magma migration is expected to be minimal, thereby facilitating the petrological interpretation of its seismic structure in terms of parental mantle processes. In the summer of 2010, a seismic refraction survey combined with multichannel seismic profiling was conducted across Shatsky Rise. Twenty eight ocean-bottom seismometers were deployed along two crossing perpendicular lines, and all of the instruments were recovered successfully, yielding a large volume of high-quality wide-angle refraction and reflection data, with the source-receiver distance often exceeding 200~km. In this contribution, we present the P-wave velocity structure of the Shatsky Rise crust, which is constructed by joint refraction and reflection travel time tomography, and also discuss its implications for the origin of Shatsky Rise.

A facile and green approach for the controlled synthesis of porous SnO₂ nanospheres: application as an efficient photocatalyst and an excellent gas sensing material.

PubMed

Manjula, P; Boppella, Ramireddy; Manorama, Sunkara V

2012-11-01

A facile and elegant methodology invoking the principles of Green Chemistry for the synthesis of porous tin dioxide nanospheres has been described. The low-temperature (∼50 °C) synthesis of SnO₂ nanoparticles and their self-assembly into organized, uniform, and monodispersed porous nanospheres with high surface area is facilitated by controlling the concentration of glucose, which acts as a stabilizing as well as structure-directing agent. A systematic control on the stannate to glucose molar concentration ratio determines the exact conditions to obtain monodispersed nanospheres, preferentially over random aggregation. Detailed characterization of the structure, morphology, and chemical composition reveals that the synthesized material, 50 nm SnO₂ porous nanospheres possess BET surface area of about 160 m²/g. Each porous nanosphere consists of a few hundred nanoparticles ∼2-3 nm in diameter with tetragonal cassiterite crystal structure. The SnO₂ nanospheres exhibit elevated photocatalytic activity toward methyl orange with good recyclability. Because of the high activity and stability of this photocatalyst, the material is ideal for applications in environmental remediation. Moreover, SnO₂ nanospheres display excellent gas sensing capabilities toward hydrogen. Surface modification of the nanospheres with Pd transforms this sensing material into a highly sensitive and selective room-temperature hydrogen sensor.

A chimeric prokaryotic pentameric ligand–gated channel reveals distinct pathways of activation

PubMed Central

Schmandt, Nicolaus; Velisetty, Phanindra; Chalamalasetti, Sreevatsa V.; Stein, Richard A.; Bonner, Ross; Talley, Lauren; Parker, Mark D.; Mchaourab, Hassane S.; Yee, Vivien C.; Lodowski, David T.

2015-01-01

Recent high resolution structures of several pentameric ligand–gated ion channels have provided unprecedented details of their molecular architecture. However, the conformational dynamics and structural rearrangements that underlie gating and allosteric modulation remain poorly understood. We used a combination of electrophysiology, double electron–electron resonance (DEER) spectroscopy, and x-ray crystallography to investigate activation mechanisms in a novel functional chimera with the extracellular domain (ECD) of amine-gated Erwinia chrysanthemi ligand–gated ion channel, which is activated by primary amines, and the transmembrane domain of Gloeobacter violaceus ligand–gated ion channel, which is activated by protons. We found that the chimera was independently gated by primary amines and by protons. The crystal structure of the chimera in its resting state, at pH 7.0 and in the absence of primary amines, revealed a closed-pore conformation and an ECD that is twisted with respect to the transmembrane region. Amine- and pH-induced conformational changes measured by DEER spectroscopy showed that the chimera exhibits a dual mode of gating that preserves the distinct conformational changes of the parent channels. Collectively, our findings shed light on both conserved and divergent features of gating mechanisms in this class of channels, and will facilitate the design of better allosteric modulators. PMID:26415570

User guide to Exploration and Graphics for RivEr Trends (EGRET) and dataRetrieval: R packages for hydrologic data

USGS Publications Warehouse

Hirsch, Robert M.; De Cicco, Laura A.

2015-01-01

Evaluating long-term changes in river conditions (water quality and discharge) is an important use of hydrologic data. To carry out such evaluations, the hydrologist needs tools to facilitate several key steps in the process: acquiring the data records from a variety of sources, structuring it in ways that facilitate the analysis, processing the data with routines that extract information about changes that may be happening, and displaying findings with graphical techniques. A pair of tightly linked R packages, called dataRetrieval and EGRET (Exploration and Graphics for RivEr Trends), have been developed for carrying out each of these steps in an integrated manner. They are designed to easily accept data from three sources: U.S. Geological Survey hydrologic data, U.S. Environmental Protection Agency (EPA) STORET data, and user-supplied flat files. The dataRetrieval package not only serves as a “front end” to the EGRET package, it can also be used to easily download many types of hydrologic data and organize it in ways that facilitate many other hydrologic applications. The EGRET package has components oriented towards the description of long-term changes in streamflow statistics (high flow, average flow, and low flow) as well as changes in water quality. For the water-quality analysis, it uses Weighted Regressions on Time, Discharge and Season (WRTDS) to describe long-term trends in both concentration and flux. EGRET also creates a wide range of graphical presentations of the water-quality data and of the WRTDS results. This report serves as a user guide to these two R packages, providing detailed guidance on installation and use of the software, documentation of the analysis methods used, as well as guidance on some of the kinds of questions and approaches that the software can facilitate.

Coping with employee, family, and student roles: evidence of dispositional conflict and facilitation tendencies.

PubMed

Hecht, Tracy D; McCarthy, Julie M

2010-07-01

Balancing multiple roles is a challenge for individuals in many sectors of the population. The purpose of this study was to test the hypothesis that individuals have dispositional tendencies to experience interrole conflict and facilitation. We also aimed to show that coping styles and life satisfaction are correlates of dispositional conflict and facilitation tendencies. Two survey studies were conducted with individuals involved in 3 life roles (i.e., employee, student, and family member; Study 1: N = 193; Study 2: N = 284). The hierarchical structure of conflict and facilitation was examined in both studies. Support for the dispositional model was found in both cases through the use of hierarchical confirmatory factor analyses. In Study 2, a longitudinal assessment of the nomological network surrounding conflict and facilitation tendencies was conducted with structural equation modeling analyses; we found that coping styles had synchronous relations with dispositional conflict and facilitation; dispositional conflict had a lagged and negative relation with life satisfaction.

Motor Task Variation Induces Structural Learning

PubMed Central

Braun, Daniel A.; Aertsen, Ad; Wolpert, Daniel M.; Mehring, Carsten

2009-01-01

Summary When we have learned a motor skill, such as cycling or ice-skating, we can rapidly generalize to novel tasks, such as motorcycling or rollerblading [1–8]. Such facilitation of learning could arise through two distinct mechanisms by which the motor system might adjust its control parameters. First, fast learning could simply be a consequence of the proximity of the original and final settings of the control parameters. Second, by structural learning [9–14], the motor system could constrain the parameter adjustments to conform to the control parameters' covariance structure. Thus, facilitation of learning would rely on the novel task parameters' lying on the structure of a lower-dimensional subspace that can be explored more efficiently. To test between these two hypotheses, we exposed subjects to randomly varying visuomotor tasks of fixed structure. Although such randomly varying tasks are thought to prevent learning, we show that when subsequently presented with novel tasks, subjects exhibit three key features of structural learning: facilitated learning of tasks with the same structure, strong reduction in interference normally observed when switching between tasks that require opposite control strategies, and preferential exploration along the learned structure. These results suggest that skill generalization relies on task variation and structural learning. PMID:19217296

Motor task variation induces structural learning.

PubMed

Braun, Daniel A; Aertsen, Ad; Wolpert, Daniel M; Mehring, Carsten

2009-02-24

When we have learned a motor skill, such as cycling or ice-skating, we can rapidly generalize to novel tasks, such as motorcycling or rollerblading [1-8]. Such facilitation of learning could arise through two distinct mechanisms by which the motor system might adjust its control parameters. First, fast learning could simply be a consequence of the proximity of the original and final settings of the control parameters. Second, by structural learning [9-14], the motor system could constrain the parameter adjustments to conform to the control parameters' covariance structure. Thus, facilitation of learning would rely on the novel task parameters' lying on the structure of a lower-dimensional subspace that can be explored more efficiently. To test between these two hypotheses, we exposed subjects to randomly varying visuomotor tasks of fixed structure. Although such randomly varying tasks are thought to prevent learning, we show that when subsequently presented with novel tasks, subjects exhibit three key features of structural learning: facilitated learning of tasks with the same structure, strong reduction in interference normally observed when switching between tasks that require opposite control strategies, and preferential exploration along the learned structure. These results suggest that skill generalization relies on task variation and structural learning.

New perspectives on the ecology of tree structure and tree communities through terrestrial laser scanning.

PubMed

Malhi, Yadvinder; Jackson, Tobias; Patrick Bentley, Lisa; Lau, Alvaro; Shenkin, Alexander; Herold, Martin; Calders, Kim; Bartholomeus, Harm; Disney, Mathias I

2018-04-06

Terrestrial laser scanning (TLS) opens up the possibility of describing the three-dimensional structures of trees in natural environments with unprecedented detail and accuracy. It is already being extensively applied to describe how ecosystem biomass and structure vary between sites, but can also facilitate major advances in developing and testing mechanistic theories of tree form and forest structure, thereby enabling us to understand why trees and forests have the biomass and three-dimensional structure they do. Here we focus on the ecological challenges and benefits of understanding tree form, and highlight some advances related to capturing and describing tree shape that are becoming possible with the advent of TLS. We present examples of ongoing work that applies, or could potentially apply, new TLS measurements to better understand the constraints on optimization of tree form. Theories of resource distribution networks, such as metabolic scaling theory, can be tested and further refined. TLS can also provide new approaches to the scaling of woody surface area and crown area, and thereby better quantify the metabolism of trees. Finally, we demonstrate how we can develop a more mechanistic understanding of the effects of avoidance of wind risk on tree form and maximum size. Over the next few years, TLS promises to deliver both major empirical and conceptual advances in the quantitative understanding of trees and tree-dominated ecosystems, leading to advances in understanding the ecology of why trees and ecosystems look and grow the way they do.

Crystal Structure of the Neutralizing Llama VHH D7 and Its Mode of HIV-1 gp120 Interaction

PubMed Central

Hinz, Andreas; Lutje Hulsik, David; Forsman, Anna; Koh, Willie Wee-Lee; Belrhali, Hassan; Gorlani, Andrea; de Haard, Hans; Weiss, Robin A.; Verrips, Theo; Weissenhorn, Winfried

2010-01-01

HIV-1 entry into host cells is mediated by the sequential binding of the envelope glycoprotein gp120 to CD4 and a chemokine receptor. Antibodies binding to epitopes overlapping the CD4-binding site on gp120 are potent inhibitors of HIV entry, such as the llama heavy chain antibody fragment VHH D7, which has cross-clade neutralizing properties and competes with CD4 and mAb b12 for high affinity binding to gp120. We report the crystal structure of the D7 VHH at 1.5 Å resolution, which reveals the molecular details of the complementarity determining regions (CDR) and substantial flexibility of CDR3 that could facilitate an induced fit interaction with gp120. Structural comparison of CDRs from other CD4 binding site antibodies suggests diverse modes of interaction. Mutational analysis identified CDR3 as a key component of gp120 interaction as determined by surface plasmon resonance. A decrease in affinity is directly coupled to the neutralization efficiency since mutations that decrease gp120 interaction increase the IC50 required for HIV-1 IIIB neutralization. Thus the structural study identifies the long CDR3 of D7 as the key determinant of interaction and HIV-1 neutralization. Furthermore, our data confirm that the structural plasticity of gp120 can accommodate multiple modes of antibody binding within the CD4 binding site. PMID:20463957

Structures of Prostacyclin Synthase and Its Complexes with Substrate Analog and Inhibitor Reveal a Ligand-specific Heme Conformation Change*s

PubMed Central

Li, Yi-Ching; Chiang, Chia-Wang; Yeh, Hui-Chun; Hsu, Pei-Yung; Whitby, Frank G.; Wang, Lee-Ho; Chan, Nei-Li

2008-01-01

Prostacyclin synthase (PGIS) is a cytochrome P450 (P450) enzyme that catalyzes production of prostacyclin from prostaglandin H2. PGIS is unusual in that it catalyzes an isomerization rather than a monooxygenation, which is typical of P450 enzymes. To understand the structural basis for prostacyclin biosynthesis in greater detail, we have determined the crystal structures of ligand-free, inhibitor (minoxidil)-bound and substrate analog U51605-bound PGIS. These structures demonstrate a stereo-specific substrate binding and suggest features of the enzyme that facilitate isomerization. Unlike most microsomal P450s, where large substrate-induced conformational changes take place at the distal side of the heme, conformational changes in PGIS are observed at the proximal side and in the heme itself. The conserved and extensive heme propionate-protein interactions seen in all other P450s, which are largely absent in the ligand-free PGIS, are recovered upon U51605 binding accompanied by water exclusion from the active site. In contrast, when minoxidil binds, the propionate-protein interactions are not recovered and water molecules are largely retained. These findings suggest that PGIS represents a divergent evolution of the P450 family, in which a heme barrier has evolved to ensure strict binding specificity for prostaglandin H2, leading to a radical-mediated isomerization with high product fidelity. The U51605-bound structure also provides a view of the substrate entrance and product exit channels. PMID:18032380

The Challenge of Producing Fiber-Based Organic Electronic Devices

PubMed Central

Könyves-Toth, Tobias; Gassmann, Andrea; von Seggern, Heinz

2014-01-01

The implementation of organic electronic devices on fibers is a challenging task, not yet investigated in detail. As was shown earlier, a direct transition from a flat device structure to a fiber substrate is in principle possible. However, a more detailed investigation of the process reveals additional complexities than just the transition in geometry. It will be shown, that the layer formation of evaporated materials behaves differently due to the multi-angled incidence on the fibers surface. In order to achieve homogenous layers the evaporation process has to be adapted. Additionally, the fiber geometry itself facilitates damaging of its surface due to mechanical impact and leads to a high surface roughness, thereby often hindering commercial fibers to be used as substrates. In this article, a treatment of commercial polymer-coated glass fibers will be demonstrated that allows for the fabrication of rather flexible organic light-emitting diodes (OLEDs) with cylindrical emission characteristics. Since OLEDs rely the most on a smooth substrate, fibers undergoing the proposed treatment are applicable for other organic electronic devices such as transistors and solar cells. Finally, the technique also supports the future fabrication of organic electronics not only in smart textiles and woven electronics but also in bent surfaces, which opens a wide range of applications. PMID:28788128

On the biophysics and kinetics of toehold-mediated DNA strand displacement

PubMed Central

Srinivas, Niranjan; Ouldridge, Thomas E.; Šulc, Petr; Schaeffer, Joseph M.; Yurke, Bernard; Louis, Ard A.; Doye, Jonathan P. K.; Winfree, Erik

2013-01-01

Dynamic DNA nanotechnology often uses toehold-mediated strand displacement for controlling reaction kinetics. Although the dependence of strand displacement kinetics on toehold length has been experimentally characterized and phenomenologically modeled, detailed biophysical understanding has remained elusive. Here, we study strand displacement at multiple levels of detail, using an intuitive model of a random walk on a 1D energy landscape, a secondary structure kinetics model with single base-pair steps and a coarse-grained molecular model that incorporates 3D geometric and steric effects. Further, we experimentally investigate the thermodynamics of three-way branch migration. Two factors explain the dependence of strand displacement kinetics on toehold length: (i) the physical process by which a single step of branch migration occurs is significantly slower than the fraying of a single base pair and (ii) initiating branch migration incurs a thermodynamic penalty, not captured by state-of-the-art nearest neighbor models of DNA, due to the additional overhang it engenders at the junction. Our findings are consistent with previously measured or inferred rates for hybridization, fraying and branch migration, and they provide a biophysical explanation of strand displacement kinetics. Our work paves the way for accurate modeling of strand displacement cascades, which would facilitate the simulation and construction of more complex molecular systems. PMID:24019238

On the biophysics and kinetics of toehold-mediated DNA strand displacement.

PubMed

Srinivas, Niranjan; Ouldridge, Thomas E; Sulc, Petr; Schaeffer, Joseph M; Yurke, Bernard; Louis, Ard A; Doye, Jonathan P K; Winfree, Erik

2013-12-01

Dynamic DNA nanotechnology often uses toehold-mediated strand displacement for controlling reaction kinetics. Although the dependence of strand displacement kinetics on toehold length has been experimentally characterized and phenomenologically modeled, detailed biophysical understanding has remained elusive. Here, we study strand displacement at multiple levels of detail, using an intuitive model of a random walk on a 1D energy landscape, a secondary structure kinetics model with single base-pair steps and a coarse-grained molecular model that incorporates 3D geometric and steric effects. Further, we experimentally investigate the thermodynamics of three-way branch migration. Two factors explain the dependence of strand displacement kinetics on toehold length: (i) the physical process by which a single step of branch migration occurs is significantly slower than the fraying of a single base pair and (ii) initiating branch migration incurs a thermodynamic penalty, not captured by state-of-the-art nearest neighbor models of DNA, due to the additional overhang it engenders at the junction. Our findings are consistent with previously measured or inferred rates for hybridization, fraying and branch migration, and they provide a biophysical explanation of strand displacement kinetics. Our work paves the way for accurate modeling of strand displacement cascades, which would facilitate the simulation and construction of more complex molecular systems.

[Physiotherapy and ergotherapy are indispensable. Concrete prescription of remedies - without recourse].

PubMed

Engel, J-M

2012-07-01

Physical therapy and occupational therapy are essential for the treatment of inflammatory rheumatic diseases equal in rank to any drug therapy. They have enough evidence and are part of all current guidelines even if mostly not specified. In the German social security system the doctor prescribing physical therapy or occupational therapy has to act according to the different rules and forms as described in the current "Heilmittel Richtlinie" (Remedy directive) effective since July 2011. The multiple formal conditions and requirements of prescriptions are described in detail. Of special interest is that the global diagnosis of rheumatoid arthritis can no longer be used as the reason or justification for the individual prescription but detailed sub-diagnoses, regarding the essential ICF domains of structural damage, functional impairment, activity limitation and participation restriction as well as individual context factors are necessary. Of special interest is the fact that the prescribing doctor is no longer responsible for the formal correctness of prescriptions but the performing therapist, who will not be reimbursed if the prescription shows even minor formal errors. Another important improvement is the newly introduced long-term prescription of physical and occupational therapy. This facilitates the application of these therapies in the multimodal treatment regimen of rheumatic diseases.

Use of a Passive Reaction Wheel Jitter Isolation System to Meet the Advanced X-Ray Astrophysics Facility Imaging Performance Requirements

NASA Technical Reports Server (NTRS)

Pendergast, Karl J.; Schauwecker, Christopher J.

1998-01-01

Third in the series of NASA great observatories, the Advanced X-Ray Astrophysics Facility (AXAF) is scheduled for launch from the Space Shuttle in November of 1998. Following in the path of the Hubble Space Telescope and the Compton Gamma Ray Observatory, this observatory will image light at X-ray wavelengths, facilitating the detailed study of such phenomena as supernovae and quasars. The AXAF project is sponsored by the Marshall Space Flight Center in Huntsville, Alabama. Because of exacting requirements on the performance of the AXAF optical system, it was necessary to reduce the transmission of reaction wheel jitter disturbances to the observatory. This reduction was accomplished via use of a passive mechanical isolation system to interface the reaction wheels with the spacecraft central structure. In addition to presenting a description of the spacecraft, the isolation system, and the key image quality requirement flowdown, this paper details the analyses performed in support of system-level imaging performance requirement verification. These analyses include the identification of system-level requirement suballocations, quantification of imaging and pointing performance, and formulation of unit-level isolation system transmissibility requirements. Given in comparison to the non-isolated system imaging performance, the results of these analyses clearly illustrate the effectiveness of an innovative reaction wheel passive isolation system.

Parent Involvement Facilitators: Unlocking Social Capital Wealth

ERIC Educational Resources Information Center

Ferrara, Margaret M.

2015-01-01

This case study provides an overview of a family outreach intervention that supports student retention in school through a school-home communication link. This intervention structure, which employs staff appropriately called parent involvement facilitators (PIFs), is one that school districts have employed to facilitate family engagement in…

Learners' Perceptions on the Structure and Usefulness of E-Resources for the Thesis Courses

ERIC Educational Resources Information Center

Aghaee, Naghmeh; Hansson, Henrik; Tedre, Matti; Drougge, Ulrika

2014-01-01

The use of information and communication technology (ICT) in education is a way to facilitate interaction and accessing information for learning in higher education. However, finding a set of structured e-resources to facilitate learning within specific courses is still a big challenge in most higher education institutions. This includes the…

Evaluating the roles of detailed endocardial structures on right ventricular haemodynamics by means of CFD simulations.

PubMed

Sacco, Federica; Paun, Bruno; Lehmkuhl, Oriol; Iles, Tinen L; Iaizzo, Paul A; Houzeaux, Guillaume; Vázquez, Mariano; Butakoff, Constantine; Aguado-Sierra, Jazmin

2018-06-11

Computational modelling plays an important role in right ventricular (RV) haemodynamic analysis. However, current approaches employ smoothed ventricular anatomies. The aim of this study is to characterise RV haemodynamics including detailed endocardial structures like trabeculae, moderator band and papillary muscles (PMs). Four paired detailed and smoothed RV endocardium models (two male and two female) were reconstructed from ex-vivo human hearts high-resolution magnetic resonance images (MRI). Detailed models include structures with ≥1 mm 2 cross-sectional area. Haemodynamic characterisation was done by computational fluid dynamics (CFD) simulations with steady and transient inflows, using high performance computing (HPC). The differences between the flows in smoothed and detailed models were assessed using Q-criterion for vorticity quantification, the pressure drop between inlet and outlet, and the wall shear stress (WSS). Results demonstrated that detailed endocardial structures increase the degree of intra-ventricular pressure drop, decrease the WSS and disrupt the dominant vortex creating secondary small vortices. Increasingly turbulent blood flow was observed in the detailed RVs. Female RVs were less trabeculated and presented lower pressure drops than the males. In conclusion, neglecting endocardial structures in RV haemodynamic models may lead to inaccurate conclusions about the pressures, stresses, and blood flow behaviour in the cavity. This article is protected by copyright. All rights reserved.

FABRIC FILTER MODEL FORMAT CHANGE; VOLUME 1. DETAILED TECHNICAL REPORT

EPA Science Inventory

The report describes an improved mathematical model for use by control personnel to determine the adequacy of existing or proposed filter systems designed to minimize coal fly ash emissions. Several time-saving steps have been introduced to facilitate model application by Agency ...

Exploring Consumer Literacy

ERIC Educational Resources Information Center

Moore, Virginia; Sumrall, William; Mott, Michael; Mitchell, Elizabeth; Theobald, Becky

2015-01-01

Methods for facilitating students' standards-based consumer literacy are addressed via the use of problem solving with food and product labels. Fifth graders will be able to: (1) provide detailed analysis of food and product labels; (2) understand large themes, including production, distribution, and consumption; and (3) explore consumer…

Secondary foundation species as drivers of trophic and functional diversity: evidence from a tree-epiphyte system.

PubMed

Angelini, Christine; Silliman, Brian R

2014-01-01

Facilitation cascades arise where primary foundation species facilitate secondary (dependent) foundation species, and collectively, they increase habitat complexity and quality to enhance biodiversity. Whether such phenomena occur in nonmarine systems and if secondary foundation species enhance food web structure (e.g., support novel feeding guilds) and ecosystem function (e.g., provide nursery for juveniles) remain unclear. Here we report on field experiments designed to test whether trees improve epiphyte survival and epiphytes secondarily increase the number and diversity of adult and juvenile invertebrates in a potential live oak-Tillandsia usneoides (Spanish moss) facilitation cascade. Our results reveal that trees reduce physical stress to facilitate Tillandsia, which, in turn, reduces desiccation and predation stress to facilitate invertebrates. In experimental removals, invertebrate total density, juvenile density, species richness and H' diversity were 16, 60, 1.7, and 1.5 times higher, and feeding guild richness and H' were 5 and 11 times greater in Tillandsia-colonized relative to Tillandsia-removal limb plots. Tillandsia enhanced communities similarly in a survey across the southeastern United States. These findings reveal that a facilitation cascade organizes this widespread terrestrial assemblage and expand the role of secondary foundation species as drivers of trophic structure and ecosystem function. We conceptualize the relationship between foundation species' structural attributes and associated species abundance and composition in a Foundation Species-Biodiversity (FSB) model. Importantly, the FSB predicts that, where secondary foundation species form expansive and functionally distinct structures that increase habitat availability and complexity within primary foundation species, they generate and maintain hot spots of biodiversity and trophic interactions.

Designing a Mobile Health App for Patients With Dysphagia Following Head and Neck Cancer: A Qualitative Study

PubMed Central

Constantinescu, Gabriela; Loewen, Irene; King, Ben; Brodt, Chris; Hodgetts, William

2017-01-01

Background Adherence to swallowing rehabilitation exercises is important to develop and maintain functional improvement, yet more than half of head and neck cancer (HNC) patients report having difficulty adhering to prescribed regimens. Health apps with game elements have been used in other health domains to motivate and engage patients. Understanding the factors that impact adherence may allow for more effective gamified solutions. Objective The aim of our study was to (1) identify self-reported factors that influence adherence to conventional home therapy without a mobile device in HNC patients and (2) identify appealing biofeedback designs that could be used in a health app. Methods A total of 10 (4 females) HNC patients (mean=60.1 years) with experience completing home-based rehabilitation programs were recruited. Thematic analysis of semi-structured interviews was used to answer the first objective. Convergent interviews were used to obtain reactions to biofeedback designs. Results Facilitators and barriers of adherence to home therapy were described through 6 themes: patient perceptions on outcomes and progress, clinical appointments, cancer treatment, rehabilitation program, personal factors, and connection. App visuals that provide feedback on performance during swallowing exercises should offer an immediate representation of effort relative to a goal. Simple, intuitive graphics were preferred over complex, abstract ones. Continued engagement with the app could be facilitated by tracking progress and by using visuals that build structures with each use. Conclusions This is a detailed documentation of the initial steps in designing a health app for a specific patient group. Results revealed the importance of patient engagement in early stages of app development. PMID:28582245

UPLC-MS-ELSD-PDA as a powerful dereplication tool to facilitate compound identification from small-molecule natural product libraries.

PubMed

Yang, Jin; Liang, Qian; Wang, Mei; Jeffries, Cynthia; Smithson, David; Tu, Ying; Boulos, Nidal; Jacob, Melissa R; Shelat, Anang A; Wu, Yunshan; Ravu, Ranga Rao; Gilbertson, Richard; Avery, Mitchell A; Khan, Ikhlas A; Walker, Larry A; Guy, R Kiplin; Li, Xing-Cong

2014-04-25

The generation of natural product libraries containing column fractions, each with only a few small molecules, using a high-throughput, automated fractionation system, has made it possible to implement an improved dereplication strategy for selection and prioritization of leads in a natural product discovery program. Analysis of databased UPLC-MS-ELSD-PDA information of three leads from a biological screen employing the ependymoma cell line EphB2-EPD generated details on the possible structures of active compounds present. The procedure allows the rapid identification of known compounds and guides the isolation of unknown compounds of interest. Three previously known flavanone-type compounds, homoeriodictyol (1), hesperetin (2), and sterubin (3), were identified in a selected fraction derived from the leaves of Eriodictyon angustifolium. The lignan compound deoxypodophyllotoxin (8) was confirmed to be an active constituent in two lead fractions derived from the bark and leaves of Thuja occidentalis. In addition, two new but inactive labdane-type diterpenoids with an uncommon triol side chain were also identified as coexisting with deoxypodophyllotoxin in a lead fraction from the bark of T. occidentalis. Both diterpenoids were isolated in acetylated form, and their structures were determined as 14S,15-diacetoxy-13R-hydroxylabd-8(17)-en-19-oic acid (9) and 14R,15-diacetoxy-13S-hydroxylabd-8(17)-en-19-oic acid (10), respectively, by spectroscopic data interpretation and X-ray crystallography. This work demonstrates that a UPLC-MS-ELSD-PDA database produced during fractionation may be used as a powerful dereplication tool to facilitate compound identification from chromatographically tractable small-molecule natural product libraries.

INTERIOR; DETAIL OF ROOF FRAMING STRUCTURE, LOOKING SOUTHWEST. Naval ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

INTERIOR; DETAIL OF ROOF FRAMING STRUCTURE, LOOKING SOUTHWEST. - Naval Computer & Telecommunications Area Master Station, Eastern Pacific, Radio Transmitter Facility Lualualei, Helix House No. 2, Base of Radio Antenna Structure No. 427, Makaha, Honolulu County, HI

Facilitation and practice in verb acquisition.

PubMed

Keren-Portnoy, Tamar

2006-08-01

This paper presents a model of syntax acquisition, whose main points are as follows: Syntax is acquired in an item-based manner; early learning facilitates subsequent learning--as evidenced by the accelerating rate of new verbs entering a given structure; and mastery of syntactic knowledge is typically achieved through practice--as evidenced by intensive use and common word order errors--and this slows down learning during the early stages of acquiring a structure. The facilitation and practice hypotheses were tested on naturalistic production samples of six Hebrew-acquiring children ranging from ages 1;1 to 2;7 (average ages 1;6 to 2;4 months). Results show that most structures did in fact accelerate; the notion of 'practice' is supported by the inverse correlation found between number of verbs and number of errors in the earliest productions in a given structure; and the absence of acceleration in a minority of the structures is due to the fact that they involve relatively less practice.

Proton-coupled sugar transport in the prototypical major facilitator superfamily protein XylE

PubMed Central

Wisedchaisri, Goragot; Park, Min-Sun; Iadanza, Matthew G.; Zheng, Hongjin; Gonen, Tamir

2014-01-01

The major facilitator superfamily (MFS) is the largest collection of structurally related membrane proteins that transport a wide array of substrates. The proton-coupled sugar transporter XylE is the first member of the MFS that has been structurally characterized in multiple transporting conformations, including both the outward and inward-facing states. Here we report the crystal structure of XylE in a new inward-facing open conformation, allowing us to visualize the rocker-switch movement of the N-domain against the C-domain during the transport cycle. Using molecular dynamics simulation, and functional transport assays, we describe the movement of XylE that facilitates sugar translocation across a lipid membrane and identify the likely candidate proton-coupling residues as the conserved Asp27 and Arg133. This study addresses the structural basis for proton-coupled substrate transport and release mechanism for the sugar porter family of proteins. PMID:25088546

Structural factors in HIV prevention: concepts, examples, and implications for research.

PubMed

Sumartojo, E

2000-06-01

HIV-prevention behavior is affected by the environment as well as by characteristics of individuals at risk. HIV-related structural factors are defined as barriers to, or facilitators of, an individual's HIV prevention behaviors; they may relate to economic, social, policy, organizational or other aspects of the environment. A relatively small number of intervention studies demonstrates the potential of structural interventions to increase HIV prevention in the United States and internationally. The promise of structural interventions has also been shown in studies of interventions to prevent disease or promote public health in areas other than HIV. Frameworks help define and exemplify structural barriers and facilitators for HIV prevention. One framework developed at Centers for Disease Control and Prevention gives examples of structural facilitators in terms of the economic resources, policy supports, societal attitudes, and organizational structures and functions associated with governments, service organizations, businesses, workforce organizations, faith communities, justice systems, media organizations, educational systems, and healthcare systems. Frameworks should assist researchers and health officials to identify important areas for structural research and programming. A structural approach is timely and innovative. Despite limitations, including the challenge of a new perspective on prevention and the difficulty of evaluating their effects, researchers and public health officials are urged to pursue structural interventions to prevent HIV.

Bioethics education in clinical settings: theory and practice of the dilemma method of moral case deliberation.

PubMed

Stolper, Margreet; Molewijk, Bert; Widdershoven, Guy

2016-07-22

Moral Case Deliberation is a specific form of bioethics education fostering professionals' moral competence in order to deal with their moral questions. So far, few studies focus in detail on Moral Case Deliberation methodologies and their didactic principles. The dilemma method is a structured and frequently used method in Moral Case Deliberation that stimulates methodological reflection and reasoning through a systematic dialogue on an ethical issue experienced in practice. In this paper we present a case-study of a Moral Case Deliberation with the dilemma method in a health care institution for people with an intellectual disability, describing the theoretical background and the practical application of the dilemma method. The dilemma method focuses on moral experiences of participants concerning a concrete dilemma in practice. By an in-depth description of each of the steps of the deliberation process, we elucidate the educational value and didactics of this specific method. The didactics and methodical steps of the dilemma method both supported and structured the dialogical reflection process of the participants. The process shows that the participants learned to recognize the moral dimension of the issue at stake and were able to distinguish various perspectives and reasons in a systematic manner. The facilitator played an important role in the learning process of the participants, by assisting them in focusing on and exploring moral aspects of the case. The reflection and learning process, experienced by the participants, shows competency-based characteristics. The role of the facilitator is that of a Socratic teacher with specific knowledge and skills, fostering reflection, inquiry and dialogue. The specific didactics of the dilemma method is well suited for teaching bioethics in clinical settings. The dilemma method follows an inductive learning approach through a dialogical moral inquiry in which participants develop not only knowledge but also skills, attitude and character. The role of a trained facilitator and a specific view on teaching and practicing ethics are essential when using the dilemma method in teaching health care professionals how to reflect on their own moral issues in practice.

Correlation of lattice defects and thermal processing in the crystallization of titania nanotube arrays

NASA Astrophysics Data System (ADS)

Hosseinpour, Pegah M.; Yung, Daniel; Panaitescu, Eugen; Heiman, Don; Menon, Latika; Budil, David; Lewis, Laura H.

2014-12-01

Titania nanotubes have the potential to be employed in a wide range of energy-related applications such as solar energy-harvesting devices and hydrogen production. As the functionality of titania nanostructures is critically affected by their morphology and crystallinity, it is necessary to understand and control these factors in order to engineer useful materials for green applications. In this study, electrochemically-synthesized titania nanotube arrays were thermally processed in inert and reducing environments to isolate the role of post-synthesis processing conditions on the crystallization behavior, electronic structure and morphology development in titania nanotubes, correlated with the nanotube functionality. Structural and calorimetric studies revealed that as-synthesized amorphous nanotubes crystallize to form the anatase structure in a three-stage process that is facilitated by the creation of structural defects. It is concluded that processing in a reducing gas atmosphere versus in an inert environment provides a larger unit cell volume and a higher concentration of Ti3+ associated with oxygen vacancies, thereby reducing the activation energy of crystallization. Further, post-synthesis annealing in either reducing or inert atmospheres produces pronounced morphological changes, confirming that the nanotube arrays thermally transform into a porous morphology consisting of a fragmented tubular architecture surrounded by a network of connected nanoparticles. This study links explicit data concerning morphology, crystallization and defects, and shows that the annealing gas environment determines the details of the crystal structure, the electronic structure and the morphology of titania nanotubes. These factors, in turn, impact the charge transport and consequently the functionality of these nanotubes as photocatalysts.

Delineating the joint hierarchical structure of clinical and personality disorders in an outpatient psychiatric sample.

PubMed

Forbes, Miriam K; Kotov, Roman; Ruggero, Camilo J; Watson, David; Zimmerman, Mark; Krueger, Robert F

2017-11-01

A large body of research has focused on identifying the optimal number of dimensions - or spectra - to model individual differences in psychopathology. Recently, it has become increasingly clear that ostensibly competing models with varying numbers of spectra can be synthesized in empirically derived hierarchical structures. We examined the convergence between top-down (bass-ackwards or sequential principal components analysis) and bottom-up (hierarchical agglomerative cluster analysis) statistical methods for elucidating hierarchies to explicate the joint hierarchical structure of clinical and personality disorders. Analyses examined 24 clinical and personality disorders based on semi-structured clinical interviews in an outpatient psychiatric sample (n=2900). The two methods of hierarchical analysis converged on a three-tier joint hierarchy of psychopathology. At the lowest tier, there were seven spectra - disinhibition, antagonism, core thought disorder, detachment, core internalizing, somatoform, and compulsivity - that emerged in both methods. These spectra were nested under the same three higher-order superspectra in both methods: externalizing, broad thought dysfunction, and broad internalizing. In turn, these three superspectra were nested under a single general psychopathology spectrum, which represented the top tier of the hierarchical structure. The hierarchical structure mirrors and extends upon past research, with the inclusion of a novel compulsivity spectrum, and the finding that psychopathology is organized in three superordinate domains. This hierarchy can thus be used as a flexible and integrative framework to facilitate psychopathology research with varying levels of specificity (i.e., focusing on the optimal level of detailed information, rather than the optimal number of factors). Copyright © 2017 Elsevier Inc. All rights reserved.

Developing methods for systematic reviewing in health services delivery and organisation

PubMed Central

Alborz, Alison; McNally, Rosalind

2007-01-01

Objectives To develop methods to facilitate the ‘systematic’ review of evidence from a range of methodologies on diffuse or ‘soft’ topics, as exemplified by ‘access to healthcare’. Data sources 28 bibliographic databases, research registers, organisational web sites or library catalogues. Reference lists from identified studies. Contact with experts and service users. Current awareness and contents alerting services in the area of learning disabilities. Review methods Inclusion criteria were English language literature from 1980 onwards, relating to people with learning disabilities of any age and all study designs. The main criteria for assessment was relevance to Guillifords’ model of access to health care which was adapted to the circumstances of people with learning disabilities. Selected studies were evaluated for scientific rigour then data was extracted and the results synthesised. Quality assessment was by an initial set of ‘generic’ quality indicators. This enabled further evidence selection before evaluation of findings according to specific criteria for qualitative, quantitative or mixed-method studies. Results 82 studies were fully evaluated. Five studies were rated ‘highly rigorous’, 22 ‘rigorous’, 46 ‘less rigorous’ and 9 ‘poor’ papers were retained as the sole evidence covering aspects of the guiding model. The majority of studies were quantitative but used only descriptive statistics. Most evidence lacked methodological detail, which often lowered final quality ratings. Conclusions The application of a consistent structure to quality evaluation can facilitate data appraisal, extraction and synthesis across a range of methodologies in diffuse or ‘soft’ topics. Synthesis can be facilitated further by using software, such as the Microsoft ‘Access’ database, for managing information. PMID:15606880

Intracardiac echo-facilitated 3D electroanatomical mapping of ventricular arrhythmias from the papillary muscles: assessing the 'fourth dimension' during ablation.

PubMed

Proietti, Riccardo; Rivera, Santiago; Dussault, Charles; Essebag, Vidal; Bernier, Martin L; Ayala-Paredes, Felix; Badra-Verdu, Mariano; Roux, Jean-François

2017-01-01

Ventricular arrhythmias (VA) originating from a papillary muscle (PM) have recently been described as a distinct clinical entity with peculiar features that make its treatment with catheter ablation challenging. Here, we report our experience using an intracardiac echo-facilitated 3D electroanatomical mapping approach in a case series of patients undergoing ablation for PM VA. Sixteen patients who underwent catheter ablation for ventricular tachycardia (VT) or symptomatic premature ventricular contractions originating from left ventricular PMs were included in the study. A total of 24 procedures (mean 1.5 per patient) were performed: 15 using a retrograde aortic approach and 9 using a transseptal approach. Integrated intracardiac ultrasound for 3D electroanatomical mapping was used in 15 of the 24 procedures. The posteromedial PM was the most frequent culprit for the clinical arrhythmia, and the body was the part of the PM most likely to be the successful site for ablation. The site of ablation was identified based on the best pace map matching the clinical arrhythmia and the site of earliest the activation. At a mean follow-up of 10.5 ± 7 months, only two patients had recurrent arrhythmias following a repeat ablation procedure. An echo-facilitated 3D electroanatomical mapping allows for real-time creation of precise geometries of cardiac chambers and endocavitary structures. This is useful during procedures such as catheter ablation of VAs originating from PMs, which require detailed representation of anatomical landmarks. Routine adoption of this technique should be considered to improve outcomes of PM VA ablation. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Developing methods for systematic reviewing in health services delivery and organization: an example from a review of access to health care for people with learning disabilities. Part 2. Evaluation of the literature--a practical guide.

PubMed

Alborz, Alison; McNally, Rosalind

2004-12-01

To develop methods to facilitate the 'systematic' review of evidence from a range of methodologies on diffuse or 'soft' topics, as exemplified by 'access to health care'. Twenty-eight bibliographic databases, research registers, organizational websites or library catalogues. Reference lists from identified studies. Contact with experts and service users. Current awareness and contents alerting services in the area of learning disabilities. Inclusion criteria were English language literature from 1980 onwards, relating to people with learning disabilities of any age and all study designs. The main criteria for assessment was relevance to Guillifords' model of access to health care which was adapted to the circumstances of people with learning disabilities. Selected studies were evaluated for scientific rigour then data was extracted and the results synthesized. Quality assessment was by an initial set of 'generic' quality indicators. This enabled further evidence selection before evaluation of findings according to specific criteria for qualitative, quantitative or mixed-method studies. Eighty-two studies were fully evaluated. Five studies were rated 'highly rigorous', 22 'rigorous', 46 'less rigorous' and nine 'poor' papers were retained as the sole evidence covering aspects of the guiding model. The majority of studies were quantitative but used only descriptive statistics. Most evidence lacked methodological detail, which often lowered final quality ratings. The application of a consistent structure to quality evaluation can facilitate data appraisal, extraction and synthesis across a range of methodologies in diffuse or 'soft' topics. Synthesis can be facilitated further by using software, such as the microsoft 'access' database, for managing information.

RNA-Puzzles: A CASP-like evaluation of RNA three-dimensional structure prediction

PubMed Central

Cruz, José Almeida; Blanchet, Marc-Frédérick; Boniecki, Michal; Bujnicki, Janusz M.; Chen, Shi-Jie; Cao, Song; Das, Rhiju; Ding, Feng; Dokholyan, Nikolay V.; Flores, Samuel Coulbourn; Huang, Lili; Lavender, Christopher A.; Lisi, Véronique; Major, François; Mikolajczak, Katarzyna; Patel, Dinshaw J.; Philips, Anna; Puton, Tomasz; Santalucia, John; Sijenyi, Fredrick; Hermann, Thomas; Rother, Kristian; Rother, Magdalena; Serganov, Alexander; Skorupski, Marcin; Soltysinski, Tomasz; Sripakdeevong, Parin; Tuszynska, Irina; Weeks, Kevin M.; Waldsich, Christina; Wildauer, Michael; Leontis, Neocles B.; Westhof, Eric

2012-01-01

We report the results of a first, collective, blind experiment in RNA three-dimensional (3D) structure prediction, encompassing three prediction puzzles. The goals are to assess the leading edge of RNA structure prediction techniques; compare existing methods and tools; and evaluate their relative strengths, weaknesses, and limitations in terms of sequence length and structural complexity. The results should give potential users insight into the suitability of available methods for different applications and facilitate efforts in the RNA structure prediction community in ongoing efforts to improve prediction tools. We also report the creation of an automated evaluation pipeline to facilitate the analysis of future RNA structure prediction exercises. PMID:22361291

Mechanism of Diphtheria Toxin Catalytic Domain Delivery to the Eukaryotic Cell Cytosol and the Cellular Factors that Directly Participate in the Process

PubMed Central

Murphy, John R.

2011-01-01

Research on diphtheria and anthrax toxins over the past three decades has culminated in a detailed understanding of their structure function relationships (e.g., catalytic (C), transmembrane (T), and receptor binding (R) domains), as well as the identification of their eukaryotic cell surface receptor, an understanding of the molecular events leading to the receptor-mediated internalization of the toxin into an endosomal compartment, and the pH triggered conformational changes required for pore formation in the vesicle membrane. Recently, a major research effort has been focused on the development of a detailed understanding of the molecular interactions between each of these toxins and eukaryotic cell factors that play an essential role in the efficient translocation of their respective catalytic domains through the trans-endosomal vesicle membrane pore and delivery into the cell cytosol. In this review, I shall focus on recent findings that have led to a more detailed understanding of the mechanism by which the diphtheria toxin catalytic domain is delivered to the eukaryotic cell cytosol. While much work remains, it is becoming increasingly clear that the entry process is facilitated by specific interactions with a number of cellular factors in an ordered sequential fashion. In addition, since diphtheria, anthrax lethal factor and anthrax edema factor all carry multiple coatomer I complex binding motifs and COPI complex has been shown to play an essential role in entry process, it is likely that the initial steps in catalytic domain entry of these divergent toxins follow a common mechanism. PMID:22069710

Impediments to the Process of Learning.

ERIC Educational Resources Information Center

Cytrynbaum, Solomon; Conran, Patricia C.

1979-01-01

Four college classrooms were observed for 40 days to determine the interaction of teacher role behaviors, student characteristics, and developmental phases of the class as a work group in disrupting or facilitating the learning process. The study's observational categories are detailed and implications for effective teaching discussed. (SJL)

77 FR 58511 - Announcement of Competition Under the America COMPETES Reauthorization Act of 2011

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-21

... electronically. To facilitate electronic delivery, the winner will need to submit financial account information... their demographic characteristics. The SUPPLEMENTARY INFORMATION section of this notice provides more detailed information about the competition. DATES: Competition began on August 31, 2012, and ends on...

76 FR 70420 - New England Fishery Management Council; Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-14

... United States Coast Guard will hold a Commercial Fishing Gear Stowage Workshop to consider actions... Fisheries Training Center, 5200 East Hospital Road, Buzzards Bay, MA 02542. The public must preregister for this workshop to facilitate entrance to this secure facility, see supplementary information for details...

VK-phantom male with 583 structures and female with 459 structures, based on the sectioned images of a male and a female, for computational dosimetry

PubMed Central

Park, Jin Seo; Jung, Yong Wook; Choi, Hyung-Do; Lee, Ae-Kyoung

2018-01-01

Abstract The anatomical structures in most phantoms are classified according to tissue properties rather than according to their detailed structures, because the tissue properties, not the detailed structures, are what is considered important. However, if a phantom does not have detailed structures, the phantom will be unreliable because different tissues can be regarded as the same. Thus, we produced the Visible Korean (VK) -phantoms with detailed structures (male, 583 structures; female, 459 structures) based on segmented images of the whole male body (interval, 1.0 mm; pixel size, 1.0 mm2) and the whole female body (interval, 1.0 mm; pixel size, 1.0 mm2), using house-developed software to analyze the text string and voxel information for each of the structures. The density of each structure in the VK-phantom was calculated based on Virtual Population and a publication of the International Commission on Radiological Protection. In the future, we will standardize the size of each structure in the VK-phantoms. If the VK-phantoms are standardized and the mass density of each structure is precisely known, researchers will be able to measure the exact absorption rate of electromagnetic radiation in specific organs and tissues of the whole body. PMID:29659988

VK-phantom male with 583 structures and female with 459 structures, based on the sectioned images of a male and a female, for computational dosimetry.

PubMed

Park, Jin Seo; Jung, Yong Wook; Choi, Hyung-Do; Lee, Ae-Kyoung

2018-05-01

The anatomical structures in most phantoms are classified according to tissue properties rather than according to their detailed structures, because the tissue properties, not the detailed structures, are what is considered important. However, if a phantom does not have detailed structures, the phantom will be unreliable because different tissues can be regarded as the same. Thus, we produced the Visible Korean (VK) -phantoms with detailed structures (male, 583 structures; female, 459 structures) based on segmented images of the whole male body (interval, 1.0 mm; pixel size, 1.0 mm2) and the whole female body (interval, 1.0 mm; pixel size, 1.0 mm2), using house-developed software to analyze the text string and voxel information for each of the structures. The density of each structure in the VK-phantom was calculated based on Virtual Population and a publication of the International Commission on Radiological Protection. In the future, we will standardize the size of each structure in the VK-phantoms. If the VK-phantoms are standardized and the mass density of each structure is precisely known, researchers will be able to measure the exact absorption rate of electromagnetic radiation in specific organs and tissues of the whole body.

Development and Delivery of a Physical Activity Intervention for People With Huntington Disease: Facilitating Translation to Clinical Practice

PubMed Central

Quinn, Lori; Trubey, Rob; Gobat, Nina; Dawes, Helen; Edwards, Rhiannon Tudor; Jones, Carys; Townson, Julia; Drew, Cheney; Kelson, Mark; Poile, Vincent; Rosser, Anne; Hood, Kerenza

2016-01-01

Background and Purpose: We studied the development and delivery of a 14-week complex physical activity intervention for people with Huntington disease, where detailed information about the intervention was fully embedded in the trial design process. Methods: Intervention Development: The intervention was developed through a series of focus groups. The findings from the focus groups informed the development of a logic model for the physical activity intervention that was broadly consistent with the framework of self-determination theory. Intervention Delivery: Key components underpinning the delivery of the intervention were implemented including a defined coach training program and intervention fidelity assessment methods. Training of coaches (physical therapists, occupational therapists, research nurses, and exercise trainers) was delivered via group and 1:1 training sessions using a detailed coach's manual, and with ongoing support via video calls, and e-mail communication as needed. Detailed documentation was provided to determine costs of intervention development and coach training. Results: Intervention delivery coaches at 8 sites across the United Kingdom participated in the face-to-face training. Self-report checklists completed by each of the coaches indicated that all components of the intervention were delivered in accordance with the protocol. Mean (standard deviation) intervention fidelity scores (n = 15), as measured using a purpose-developed rating scale, was 11 (2.4) (out of 16 possible points). Coaches' perceptions of intervention fidelity were similarly high. The total cost of developing the intervention and providing training was £30,773 ($47,042 USD). Discussion and Conclusions: An important consideration in promoting translation of clinical research into practice is the ability to convey the detailed components of how the intervention was delivered to facilitate replication if the results are favorable. This report presents an illustrative example of a physical activity intervention, including the development and the training required to deliver it. This approach has the potential to facilitate reproducibility, evidence synthesis, and implementation in clinical practice. Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A122). PMID:26863152

Structural evolution of Ti destroyable interlayer in large-size diamond film deposition by DC arc plasma jet

NASA Astrophysics Data System (ADS)

Guo, Jianchao; Li, Chengming; Liu, Jinlong; Wei, Junjun; Chen, Liangxian; Hua, Chenyi; Yan, Xiongbo

2016-05-01

The addition of titanium (Ti) interlayer was verified to reduce the residual stress of diamond films by self-fracturing and facilitate the harvest of a crack-free free-standing diamond film prepared by direct current (DC) arc plasma jet. In this study, the evolution of the Ti interlayer between large-area diamond film and substrate was studied and modeled in detail. The evolution of the interlayer was found to be relevant to the distribution of the DC arc plasma, which can be divided into three areas (arc center, arc main, and arc edge). The formation rate of titanium carbide (TiC) in the arc main was faster than in the other two areas and resulted in the preferred generation of crack in the diamond film in the arc main during cooling. Sandwich structures were formed along with the growth of TiC until the complete transformation of the Ti interlayer. The interlayer released stress via self-fracture. Avoiding uneven fragile regions that formed locally in the interlayer and achieving cooperatively released stress are crucial for the preparation of large crack-free diamond films.

Maintenance of electrostatic stabilization in altered tubulin lateral contacts may facilitate formation of helical filaments in foraminifera.

PubMed

Bassen, David M; Hou, Yubo; Bowser, Samuel S; Banavali, Nilesh K

2016-08-19

Microtubules in foraminiferan protists (forams) can convert into helical filament structures, in which longitudinal intraprotofilament interactions between tubulin heterodimers are thought to be lost, while lateral contacts across protofilaments are still maintained. The coarse geometric features of helical filaments are known through low-resolution negative stain electron microscopy (EM). In this study, geometric restraints derived from these experimental data were used to generate an average atomic-scale helical filament model, which anticipated a modest reorientation in the lateral tubulin heterodimer interface. Restrained molecular dynamics (MD) simulations of the nearest neighbor interactions combined with a Genalized Born implicit solvent model were used to assess the lateral, longitudinal, and seam contacts in 13-3 microtubules and the reoriented lateral contacts in the helical filament model. This electrostatic analysis suggests that the change in the lateral interface in the helical filament does not greatly diminish the lateral electrostatic interaction. After longitudinal dissociation, the 13-3 seam interaction is much weaker than the reoriented lateral interface in the helical filament model, providing a plausible atomic-detail explanation for seam-to-lateral contact transition that enables the transition to a helical filament structure.

Maintenance of electrostatic stabilization in altered tubulin lateral contacts may facilitate formation of helical filaments in foraminifera

NASA Astrophysics Data System (ADS)

Bassen, David M.; Hou, Yubo; Bowser, Samuel S.; Banavali, Nilesh K.

2016-08-01

Microtubules in foraminiferan protists (forams) can convert into helical filament structures, in which longitudinal intraprotofilament interactions between tubulin heterodimers are thought to be lost, while lateral contacts across protofilaments are still maintained. The coarse geometric features of helical filaments are known through low-resolution negative stain electron microscopy (EM). In this study, geometric restraints derived from these experimental data were used to generate an average atomic-scale helical filament model, which anticipated a modest reorientation in the lateral tubulin heterodimer interface. Restrained molecular dynamics (MD) simulations of the nearest neighbor interactions combined with a Genalized Born implicit solvent model were used to assess the lateral, longitudinal, and seam contacts in 13-3 microtubules and the reoriented lateral contacts in the helical filament model. This electrostatic analysis suggests that the change in the lateral interface in the helical filament does not greatly diminish the lateral electrostatic interaction. After longitudinal dissociation, the 13-3 seam interaction is much weaker than the reoriented lateral interface in the helical filament model, providing a plausible atomic-detail explanation for seam-to-lateral contact transition that enables the transition to a helical filament structure.

Development, implementation and evaluation of an interprofessional graduate program for nursing-paramedicine double-degree graduates.

PubMed

Considine, Julie; Walker, Tony; Berry, Debra

2015-11-01

Over the past decade, several Australian universities have offered a double degree in nursing and paramedicine. Mainstream employment models that facilitate integrated graduate practice in both nursing and paramedicine are currently lacking. The aim of the present study was to detail the development of the Interprofessional Graduate Program (IPG), the industrial and professional issues that required solutions, outcomes from the first pilot IPG group and future directions. The IPG was an 18-month program during which participants rotated between graduate nursing experience in emergency nursing at Northern Health, Melbourne, Australia and graduate paramedic experience with Ambulance Victoria. The first IPG with 10 participants ran from January 2011 to August 2012. A survey completed by nine of the 10 participants in March 2014 showed that all nine participants nominated Ambulance Victoria as their main employer and five participants were working casual shifts in nursing. Alternative graduate programs that span two health disciplines are feasible but hampered by rigid industrial relations structures and professional ideologies. Despite a 'purpose built' graduate program that spanned two disciplines, traditional organisational structures still hamper double-degree graduates using all of skills to full capacity, and force the selection of one dominant profession.

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

Wang, Zihan; Swantek, Andrew; Scarcelli, Riccardo

This paper focuses on detailed numerical simulations of direct injection diesel and gasoline sprays from production grade, multi-hole injectors. In a dual-fuel engine the direct injection of both the fuels can facilitate appropriate mixture preparation prior to ignition and combustion. Diesel and gasoline sprays were simulated using high-fidelity Large Eddy Simulations (LES) with the dynamic structure sub-grid scale model. Numerical predictions of liquid penetration, fuel density distribution as well as transverse integrated mass (TIM) at different axial locations versus time were compared against x-ray radiography data obtained from Argonne National Laboratory. A necessary, but often overlooked, criterion of grid-convergence ismore » ensured by using Adaptive Mesh Refinement (AMR) for both diesel and gasoline. Nine different realizations were performed and the effects of random seeds on spray behavior were investigated. Additional parametric studies under different ambient and injection conditions were performed to study their influence on global and local flow structures for gasoline sprays. It is concluded that LES can generally well capture all experimental trends and comes close to matching the x-ray data. Discrepancies between experimental and simulation results can be correlated to uncertainties in boundary and initial conditions such as rate of injection and spray and turbulent dispersion sub-model constants.« less

Event-based text mining for biology and functional genomics

PubMed Central

Thompson, Paul; Nawaz, Raheel; McNaught, John; Kell, Douglas B.

2015-01-01

The assessment of genome function requires a mapping between genome-derived entities and biochemical reactions, and the biomedical literature represents a rich source of information about reactions between biological components. However, the increasingly rapid growth in the volume of literature provides both a challenge and an opportunity for researchers to isolate information about reactions of interest in a timely and efficient manner. In response, recent text mining research in the biology domain has been largely focused on the identification and extraction of ‘events’, i.e. categorised, structured representations of relationships between biochemical entities, from the literature. Functional genomics analyses necessarily encompass events as so defined. Automatic event extraction systems facilitate the development of sophisticated semantic search applications, allowing researchers to formulate structured queries over extracted events, so as to specify the exact types of reactions to be retrieved. This article provides an overview of recent research into event extraction. We cover annotated corpora on which systems are trained, systems that achieve state-of-the-art performance and details of the community shared tasks that have been instrumental in increasing the quality, coverage and scalability of recent systems. Finally, several concrete applications of event extraction are covered, together with emerging directions of research. PMID:24907365

A New Design Strategy for Observing Lithium Oxide Growth-Evolution Interactions Using Geometric Catalyst Positioning.

PubMed

Ryu, Won-Hee; Gittleson, Forrest S; Li, Jinyang; Tong, Xiao; Taylor, André D

2016-08-10

Understanding the catalyzed formation and evolution of lithium-oxide products in Li-O2 batteries is central to the development of next-generation energy storage technology. Catalytic sites, while effective in lowering reaction barriers, often become deactivated when placed on the surface of an oxygen electrode due to passivation by solid products. Here we investigate a mechanism for alleviating catalyst deactivation by dispersing Pd catalytic sites away from the oxygen electrode surface in a well-structured anodic aluminum oxide (AAO) porous membrane interlayer. We observe the cross-sectional product growth and evolution in Li-O2 cells by characterizing products that grow from the electrode surface. Morphological and structural details of the products in both catalyzed and uncatalyzed cells are investigated independently from the influence of the oxygen electrode. We find that the geometric decoration of catalysts far from the conductive electrode surface significantly improves the reaction reversibility by chemically facilitating the oxidation reaction through local coordination with PdO surfaces. The influence of the catalyst position on product composition is further verified by ex situ X-ray photoelectron spectroscopy and Raman spectroscopy in addition to morphological studies.

Report on cascade energy relaxation from PVP to Tb3+:Bi2SiO5 nanophosphor through salicylic acid in composite polymeric film

NASA Astrophysics Data System (ADS)

Kumari, Pushpa; Dwivedi, Y.

2018-05-01

The present article reports structural and spectroscopic properties of Tb:Bi2SiO5 nanophosphors dispersed in Polyvinylpyrrolidone polymer film, in presence of Salicylic acid (SA) molecule, which acts as a sensitizer. Detailed structural and spectroscopic characterizations were carried out using X-ray diffraction patterns, Scanning Electron Microscope, Fourier Transform Infrared and Excitation and photoluminescence techniques. The mean crystallite size of Tb3+:Bi2SiO5 nanophosphor and Tb3+:Bi2SiO5 in Polyvinylpyrrolidone polymer composite was estimated ∼22 nm and ∼28 nm, respectively. We have report atleast two times enhancement in Tb3+ ions emission intensity due to the efficient energy transfer from salicylic acid molecule to Tb ions. In addition to energy transfer from salicylic acid, the Polyvinylpyrrolidone polymeric host was also reported to serve as a sensitizer for SA molecule and Tb3+ ions through a cascade energy relaxation process while exciting with 248 nm photons. On 248 nm photon excitation, atleast five improvements in Tb3+ ion emission intensity are reported. Presence of SA molecule facilitates precise colour tuning as obvious from the CIE coordinates.

Device reflectivity as a simple rule for predicting the suitability of scattering foils for improved OLED light extraction

NASA Astrophysics Data System (ADS)

Levell, Jack W.; Harkema, Stephan; Pendyala, Raghu K.; Rensing, Peter A.; Senes, Alessia; Bollen, Dirk; MacKerron, Duncan; Wilson, Joanne S.

2013-09-01

A general challenge in Organic Light Emitting Diodes (OLEDs) is to extract the light efficiently from waveguided modes within the device structure. This can be accomplished by applying an additional scattering layer to the substrate which results in outcoupling increases between 0% to <100% in external quantum efficiency. In this work, we aim to address this large variation and show that the reflectivity of the OLED is a simple and useful predictor of the efficiency of substrate scattering techniques without the need for detailed modeling. We show that by optimizing the cathode and anode structure of glass based OLEDs by using silver and an ITO free high conductive Agfa Orgacon™ PEDOT:PSS we are able to increase the external quantum efficiency of OLEDs with the same outcoupling substrates from 2.4% to 5.6%, an increase of 130%. In addition, Holst Centre and partners are developing flexible substrates with integrated light extraction features and roll to roll compatible processing techniques to enable this next step in OLED development both for lighting and display applications. These devices show promise as they are shatterproof substrates and facilitate low cost manufacture.

A new design strategy for observing lithium oxide growth-evolution interactions using geometric catalyst positioning

DOE PAGES

Ryu, Won -Hee; Gittleson, Forrest S.; Li, Jinyang; ...

2016-06-21

Understanding the catalyzed formation and evolution of lithium-oxide products in Li-O 2 batteries is central to the development of next-generation energy storage technology. Catalytic sites, while effective in lowering reaction barriers, often become deactivated when placed on the surface of an oxygen electrode due to passivation by solid products. Here we investigate a mechanism for alleviating catalyst deactivation by dispersing Pd catalytic sites away from the oxygen electrode surface in a well-structured anodic aluminum oxide (AAO) porous membrane interlayer. We observe the cross-sectional product growth and evolution in Li-O 2 cells by characterizing products that grow from the electrode surface.more » Morphological and structural details of the products in both catalyzed and uncatalyzed cells are investigated independently from the influence of the oxygen electrode. We find that the geometric decoration of catalysts far from the conductive electrode surface significantly improves the reaction reversibility by chemically facilitating the oxidation reaction through local coordination with PdO surfaces. Lastly, the influence of the catalyst position on product composition is further verified by ex situ Xray photoelectron spectroscopy and Raman spectroscopy in addition to morphological studies.« less

On the unique structure of the magnetic fields of Uranus and Neptune

NASA Technical Reports Server (NTRS)

Dolginov, Sh. SH.

1993-01-01

The magnetic fields of Uranus and Neptune, which have comparable dipole, quadrupole, and octupole harmonics, are unique in the present-day solar system, but they resemble the geomagnetic field at the epochs of excursions and reversals known from paleomagnetic data. The precession dynamo model, in which the dominant role in the generation of the planetary magnetic fields is played by external gravitational forces, allows us to propose two scenarios for the formation of the unique topology of the magnetic fields of Uranus and Neptune. In the first case, tidal flows in the 'oceans' of these two planets extend down to the depths where the matter has a noticeable electric conductivity and velocity. A hydromagnetic interaction of the moving conducting fluid with the planetary magnetic field outside the generation region results in the deformation of the field and the deceleration of the motion under the action of the radial magnetic field. In the second case, the deformation of the field facilitates drastic changes in cyclonic cells within the generation region causing instabilities that result in a multi-polar field structure, excursions, and inversions. This paper considers this problem in greater detail by using the Neptune-Triton system as an example.

Biological response of zebrafish embryos after short-term exposure to thifluzamide

NASA Astrophysics Data System (ADS)

Yang, Yang; Liu, Wenxian; Mu, Xiyan; Qi, Suzhen; Fu, Bin; Wang, Chengju

2016-12-01

Thifluzamide is a new amide fungicide, and its extensive application may have toxic effects on zebrafish. To better understand the underlying mechanism, we investigated in detail the potential toxic effects of thifluzamide on zebrafish embryos. In the present study, embryos were exposed to 0, 0.19, 1.90, and 2.85 mg/L thifluzamide for 4 days. Obvious pathological changes were found upon a histological exam, and negative changes in mitochondrial structure were observed under Transmission Electron Microscopy (TEM), which qualitatively noted the toxic effects of thifluzamide on embryos. Moreover, we quantitatively evaluated the enzyme activities [succinate dehydrogenase (SDH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), caspases], the contents of malonaldehyde (MDA) and interleukin-8 (IL-8) and the expression levels of the related genes. This study suggests that the negative changes in mitochondrial structure and SDH activity might be responsible for oxidative damage, cell apoptosis and inflammation, which would facilitate the action of these factors in cell death and might play a crucial role during toxic events. In addition to providing the first description of the mechanism of the toxic effects of thifluzamide on embryos, this study also represents a step towards using embryos to assess mitochondrial metabolism and disease.

Mapping forest canopy gaps using air-photo interpretation and ground surveys

USGS Publications Warehouse

Fox, T.J.; Knutson, M.G.; Hines, R.K.

2000-01-01

Canopy gaps are important structural components of forested habitats for many wildlife species. Recent improvements in the spatial accuracy of geographic information system tools facilitate accurate mapping of small canopy features such as gaps. We compared canopy-gap maps generated using ground survey methods with those derived from air-photo interpretation. We found that maps created from high-resolution air photos were more accurate than those created from ground surveys. Errors of omission were 25.6% for the ground-survey method and 4.7% for the air-photo method. One variable of inter est in songbird research is the distance from nests to gap edges. Distances from real and simulated nests to gap edges were longer using the ground-survey maps versus the air-photo maps, indicating that gap omission could potentially bias the assessment of spatial relationships. If research or management goals require location and size of canopy gaps and specific information about vegetation structure, we recommend a 2-fold approach. First, canopy gaps can be located and the perimeters defined using 1:15,000-scale or larger aerial photographs and the methods we describe. Mapped gaps can then be field-surveyed to obtain detailed vegetation data.

Nonparametric Online Learning Control for Soft Continuum Robot: An Enabling Technique for Effective Endoscopic Navigation

PubMed Central

Lee, Kit-Hang; Fu, Denny K.C.; Leong, Martin C.W.; Chow, Marco; Fu, Hing-Choi; Althoefer, Kaspar; Sze, Kam Yim; Yeung, Chung-Kwong

2017-01-01

Abstract Bioinspired robotic structures comprising soft actuation units have attracted increasing research interest. Taking advantage of its inherent compliance, soft robots can assure safe interaction with external environments, provided that precise and effective manipulation could be achieved. Endoscopy is a typical application. However, previous model-based control approaches often require simplified geometric assumptions on the soft manipulator, but which could be very inaccurate in the presence of unmodeled external interaction forces. In this study, we propose a generic control framework based on nonparametric and online, as well as local, training to learn the inverse model directly, without prior knowledge of the robot's structural parameters. Detailed experimental evaluation was conducted on a soft robot prototype with control redundancy, performing trajectory tracking in dynamically constrained environments. Advanced element formulation of finite element analysis is employed to initialize the control policy, hence eliminating the need for random exploration in the robot's workspace. The proposed control framework enabled a soft fluid-driven continuum robot to follow a 3D trajectory precisely, even under dynamic external disturbance. Such enhanced control accuracy and adaptability would facilitate effective endoscopic navigation in complex and changing environments. PMID:29251567

Nonparametric Online Learning Control for Soft Continuum Robot: An Enabling Technique for Effective Endoscopic Navigation.

PubMed

Lee, Kit-Hang; Fu, Denny K C; Leong, Martin C W; Chow, Marco; Fu, Hing-Choi; Althoefer, Kaspar; Sze, Kam Yim; Yeung, Chung-Kwong; Kwok, Ka-Wai

2017-12-01

Bioinspired robotic structures comprising soft actuation units have attracted increasing research interest. Taking advantage of its inherent compliance, soft robots can assure safe interaction with external environments, provided that precise and effective manipulation could be achieved. Endoscopy is a typical application. However, previous model-based control approaches often require simplified geometric assumptions on the soft manipulator, but which could be very inaccurate in the presence of unmodeled external interaction forces. In this study, we propose a generic control framework based on nonparametric and online, as well as local, training to learn the inverse model directly, without prior knowledge of the robot's structural parameters. Detailed experimental evaluation was conducted on a soft robot prototype with control redundancy, performing trajectory tracking in dynamically constrained environments. Advanced element formulation of finite element analysis is employed to initialize the control policy, hence eliminating the need for random exploration in the robot's workspace. The proposed control framework enabled a soft fluid-driven continuum robot to follow a 3D trajectory precisely, even under dynamic external disturbance. Such enhanced control accuracy and adaptability would facilitate effective endoscopic navigation in complex and changing environments.

Revealing biological information using data structuring and automated learning.

PubMed

Mohorianu, Irina; Moulton, Vincent

2010-11-01

The intermediary steps between a biological hypothesis, concretized in the input data, and meaningful results, validated using biological experiments, commonly employ bioinformatics tools. Starting with storage of the data and ending with a statistical analysis of the significance of the results, every step in a bioinformatics analysis has been intensively studied and the resulting methods and models patented. This review summarizes the bioinformatics patents that have been developed mainly for the study of genes, and points out the universal applicability of bioinformatics methods to other related studies such as RNA interference. More specifically, we overview the steps undertaken in the majority of bioinformatics analyses, highlighting, for each, various approaches that have been developed to reveal details from different perspectives. First we consider data warehousing, the first task that has to be performed efficiently, optimizing the structure of the database, in order to facilitate both the subsequent steps and the retrieval of information. Next, we review data mining, which occupies the central part of most bioinformatics analyses, presenting patents concerning differential expression, unsupervised and supervised learning. Last, we discuss how networks of interactions of genes or other players in the cell may be created, which help draw biological conclusions and have been described in several patents.

76 FR 27250 - Drawbridge Operation Regulation; Atlantic Intracoastal Waterway, Albemarle and Chesapeake Canal...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-11

... Chesapeake Canal, mile 15.2, at Chesapeake, VA. The deviation is necessary to facilitate urgent mechanical... operating regulations set out in 33 CFR 117.997(i), to facilitate urgent mechanical and structural repairs... will operate on a 4-hour opening schedule. This schedule is meant to facilitate urgent mechanical and...

Teaching Note--Constructing Critical Conversations: A Model for Facilitating Classroom Dialogue for Critical Learning

ERIC Educational Resources Information Center

Kang, Hye-Kyung; O'Neill, Peggy

2018-01-01

Discussions of power and privilege, oppression, and structural inequities in classrooms can produce complex understanding and critical analysis when facilitated effectively. In this article we present the critical conversations model for facilitating conversations that open up space for discussing such issues and encourage the development of…

Engaging stakeholder communities as body image intervention partners: The Body Project as a case example.

PubMed

Becker, Carolyn Black; Perez, Marisol; Kilpela, Lisa Smith; Diedrichs, Phillippa C; Trujillo, Eva; Stice, Eric

2017-04-01

Despite recent advances in developing evidence-based psychological interventions, substantial changes are needed in the current system of intervention delivery to impact mental health on a global scale (Kazdin & Blase, 2011). Prevention offers one avenue for reaching large populations because prevention interventions often are amenable to scaling-up strategies, such as task-shifting to lay providers, which further facilitate community stakeholder partnerships. This paper discusses the dissemination and implementation of the Body Project, an evidence-based body image prevention program, across 6 diverse stakeholder partnerships that span academic, non-profit and business sectors at national and international levels. The paper details key elements of the Body Project that facilitated partnership development, dissemination and implementation, including use of community-based participatory research methods and a blended train-the-trainer and task-shifting approach. We observed consistent themes across partnerships, including: sharing decision making with community partners, engaging of community leaders as gatekeepers, emphasizing strengths of community partners, working within the community's structure, optimizing non-traditional and/or private financial resources, placing value on cost-effectiveness and sustainability, marketing the program, and supporting flexibility and creativity in developing strategies for evolution within the community and in research. Ideally, lessons learned with the Body Project can be generalized to implementation of other body image and eating disorder prevention programs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Researcher perspectives on competencies of return-to-work coordinators.

PubMed

Gardner, Bethany T; Pransky, Glenn; Shaw, William S; Hong, Qua Nha; Loisel, Patrick

2010-01-01

Return-to-work (RTW) coordination programs are successful in reducing long-term work disability, but research reports have not adequately described the role and competencies of the RTW coordinator. This study was conducted to clarify the impact of RTW coordinators, and competencies (knowledge, skills, and attitudes) required to achieve optimal RTW outcomes in injured workers. Studies involving RTW coordination for injured workers were identified through literature review. Semi-structured interviews were conducted with 12 principal investigators to obtain detailed information about the RTW coordinator role and competencies not included in published articles. Interview results were synthesized into principal conceptual groups by affinity mapping. All investigators strongly endorsed the role of RTW coordinator as key to the program's success. Affinity mapping identified 10 groups of essential competencies: (1) individual traits/qualities, (2) relevant knowledge base, (3) RTW focus and attitude, (4) organizational/administrative skills, (5) assessment skills, (6) communication skills, (7) interpersonal relationship skills, (8) conflict resolution skills, (9) problem-solving skills, and (10) RTW facilitation skills. Specific consensus competencies were identified within each affinity group. Most investigators endorsed similar competencies, although there was some variation by setting or scope of RTW intervention. RTW coordinators are essential contributors in RTW facilitation programs. This study identified specific competencies required to achieve success. More emphasis on mentorship and observation will be required to develop and evaluate necessary skills in this area.

Visualizing the kinetic power stroke that drives proton-coupled Zn(II) transport

PubMed Central

Gupta, Sayan; Chai, Jin; Cheng, Jie; D'Mello, Rhijuta; Chance, Mark R.; Fu, Dax

2014-01-01

The proton gradient is a principal energy source for respiration-dependent active transport, but the structural mechanisms of proton-coupled transport processes are poorly understood. YiiP is a proton-coupled zinc transporter found in the cytoplasmic membrane of E. coli, and the transport-site of YiiP receives protons from water molecules that gain access to its hydrophobic environment and transduces the energy of an inward proton gradient to drive Zn(II) efflux1,2. This membrane protein is a well characterized member3-7 of the protein family of cation diffusion facilitators (CDFs) that occurs at all phylogenetic levels8-10. X-ray mediated hydroxyl radical labeling of YiiP and mass spectrometric analysis showed that Zn(II) binding triggered a highly localized, all-or-none change of water accessibility to the transport-site and an adjacent hydrophobic gate. Millisecond time-resolved dynamics revealed a concerted and reciprocal pattern of accessibility changes along a transmembrane helix, suggesting a rigid-body helical reorientation linked to Zn(II) binding that triggers the closing of the hydrophobic gate. The gated water access to the transport-site enables a stationary proton gradient to facilitate the conversion of zinc binding energy to the kinetic power stroke of a vectorial zinc transport. The kinetic details provide energetic insights into a proton-coupled active transport reaction. PMID:25043033

Understanding ionic conductivity trends in polyborane solid electrolytes from ab initio molecular dynamics

NASA Astrophysics Data System (ADS)

Varley, Joel; Kweon, Kyoung; Mehta, Prateek; Shea, Patrick; Heo, Tae Wook; Stavila, Vitalie; Udovic, Terrence; Wood, Brandon

Polyborane salts based on B12H122- , B10H102- , and their carboborane counterparts CB11H12- and CB9H10- demonstrate extraordinary Li and Na superionic conductivity that make them attractive as electrolytes in all-solid-state batteries. Their rich chemical and structural diversity creates a versatile design space that could be used to optimize materials with even higher conductivity at lower temperatures; however, many mechanistic details remain enigmatic, including reasons why certain modifications lead to improved performance. Here, we use extensive ab initio molecular dynamics simulations to broadly explore the dependence of ionic conductivity on cation/anion pair combinations for Li and Na polyborane salts. Further simulations based on Li2B12H12 as a model system are used to probe the additional influence of local perturbations, including modifications to chemistry, stoichiometry, and composition. Carbon doping, anion alloying, and cation off-stoichiometry are found to be favorable because they introduce intrinsic disorder, which facilitates local deviations from the expected cation population. Anion reorientations are also discovered to be critical for conduction, with benefits associated with lattice expansion traceable to the facilitation of anion rotation at larger volumes. This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

Development and Implementation of Efficiency-Improving Analysis Methods for the SAGE III on ISS Thermal Model Originating

NASA Technical Reports Server (NTRS)

Liles, Kaitlin; Amundsen, Ruth; Davis, Warren; Scola, Salvatore; Tobin, Steven; McLeod, Shawn; Mannu, Sergio; Guglielmo, Corrado; Moeller, Timothy

2013-01-01

The Stratospheric Aerosol and Gas Experiment III (SAGE III) instrument is the fifth in a series of instruments developed for monitoring aerosols and gaseous constituents in the stratosphere and troposphere. SAGE III will be delivered to the International Space Station (ISS) via the SpaceX Dragon vehicle in 2015. A detailed thermal model of the SAGE III payload has been developed in Thermal Desktop (TD). Several novel methods have been implemented to facilitate efficient payload-level thermal analysis, including the use of a design of experiments (DOE) methodology to determine the worst-case orbits for SAGE III while on ISS, use of TD assemblies to move payloads from the Dragon trunk to the Enhanced Operational Transfer Platform (EOTP) to its final home on the Expedite the Processing of Experiments to Space Station (ExPRESS) Logistics Carrier (ELC)-4, incorporation of older models in varying unit sets, ability to change units easily (including hardcoded logic blocks), case-based logic to facilitate activating heaters and active elements for varying scenarios within a single model, incorporation of several coordinate frames to easily map to structural models with differing geometries and locations, and streamlined results processing using an Excel-based text file plotter developed in-house at LaRC. This document presents an overview of the SAGE III thermal model and describes the development and implementation of these efficiency-improving analysis methods.

Extremely high resolution 3D electrical resistivity tomography to depict archaeological subsurface structures

NASA Astrophysics Data System (ADS)

Al-Saadi, Osamah; Schmidt, Volkmar; Becken, Michael; Fritsch, Thomas

2017-04-01

Electrical resistivity tomography (ERT) methods have been increasingly used in various shallow depth archaeological prospections in the last few decades. These non-invasive techniques are very useful in saving time, costs, and efforts. Both 2D and 3D ERT techniques are used to obtain detailed images of subsurface anomalies. In two surveyed areas near Nonnweiler (Germany), we present the results of the full 3D setup with a roll-along technique and of the quasi-3D setup (parallel and orthogonal profiles in dipole-dipole configuration). In area A, a dipole-dipole array with 96 electrodes in a uniform rectangular survey grid has been used in full 3D to investigate a presumed Roman building. A roll-along technique has been utilized to cover a large part of the archaeological site with an electrode spacing of 1 meter and with 0.5 meter for a more detailed image. Additional dense parallel 2D profiles have been carried out in dipole-dipole array with 0.25 meter electrode spacing and 0.25 meter between adjacent profiles in both direction for higher- resolution subsurface images. We have designed a new field procedure, which used an electrode array fixed in a frame. This facilitates efficient field operation, which comprised 2376 electrode positions. With the quasi 3D imaging, we confirmed the full 3D inversion model but at a much better resolution. In area B, dense parallel 2D profiles were directly used to survey the second target with also 0.25 meter electrode spacing and profiles separation respectively. The same field measurement design has been utilized and comprised 9648 electrode positions in total. The quasi-3D inversion results clearly revealed the main structures of the Roman construction. These ERT inversion results coincided well with the archaeological excavation, which has been done in some parts of this area. The ERT result successfully images parts from the walls and also smaller internal structures of the Roman building.

Multiscale morphological filtering for analysis of noisy and complex images

NASA Astrophysics Data System (ADS)

Kher, A.; Mitra, S.

Images acquired with passive sensing techniques suffer from illumination variations and poor local contrasts that create major difficulties in interpretation and identification tasks. On the other hand, images acquired with active sensing techniques based on monochromatic illumination are degraded with speckle noise. Mathematical morphology offers elegant techniques to handle a wide range of image degradation problems. Unlike linear filters, morphological filters do not blur the edges and hence maintain higher image resolution. Their rich mathematical framework facilitates the design and analysis of these filters as well as their hardware implementation. Morphological filters are easier to implement and are more cost effective and efficient than several conventional linear filters. Morphological filters to remove speckle noise while maintaining high resolution and preserving thin image regions that are particularly vulnerable to speckle noise were developed and applied to SAR imagery. These filters used combination of linear (one-dimensional) structuring elements in different (typically four) orientations. Although this approach preserves more details than the simple morphological filters using two-dimensional structuring elements, the limited orientations of one-dimensional elements approximate the fine details of the region boundaries. A more robust filter designed recently overcomes the limitation of the fixed orientations. This filter uses a combination of concave and convex structuring elements. Morphological operators are also useful in extracting features from visible and infrared imagery. A multiresolution image pyramid obtained with successive filtering and a subsampling process aids in the removal of the illumination variations and enhances local contrasts. A morphology-based interpolation scheme was also introduced to reduce intensity discontinuities created in any morphological filtering task. The generality of morphological filtering techniques in extracting information from a wide variety of images obtained with active and passive sensing techniques is discussed. Such techniques are particularly useful in obtaining more information from fusion of complex images by different sensors such as SAR, visible, and infrared.

Multiscale Morphological Filtering for Analysis of Noisy and Complex Images

NASA Technical Reports Server (NTRS)

Kher, A.; Mitra, S.

1993-01-01

Images acquired with passive sensing techniques suffer from illumination variations and poor local contrasts that create major difficulties in interpretation and identification tasks. On the other hand, images acquired with active sensing techniques based on monochromatic illumination are degraded with speckle noise. Mathematical morphology offers elegant techniques to handle a wide range of image degradation problems. Unlike linear filters, morphological filters do not blur the edges and hence maintain higher image resolution. Their rich mathematical framework facilitates the design and analysis of these filters as well as their hardware implementation. Morphological filters are easier to implement and are more cost effective and efficient than several conventional linear filters. Morphological filters to remove speckle noise while maintaining high resolution and preserving thin image regions that are particularly vulnerable to speckle noise were developed and applied to SAR imagery. These filters used combination of linear (one-dimensional) structuring elements in different (typically four) orientations. Although this approach preserves more details than the simple morphological filters using two-dimensional structuring elements, the limited orientations of one-dimensional elements approximate the fine details of the region boundaries. A more robust filter designed recently overcomes the limitation of the fixed orientations. This filter uses a combination of concave and convex structuring elements. Morphological operators are also useful in extracting features from visible and infrared imagery. A multiresolution image pyramid obtained with successive filtering and a subsampling process aids in the removal of the illumination variations and enhances local contrasts. A morphology-based interpolation scheme was also introduced to reduce intensity discontinuities created in any morphological filtering task. The generality of morphological filtering techniques in extracting information from a wide variety of images obtained with active and passive sensing techniques is discussed. Such techniques are particularly useful in obtaining more information from fusion of complex images by different sensors such as SAR, visible, and infrared.

36. ARCHITECTURAL AND STRUCTURAL DETAILS OF ELEVATOR HOUSING, NaK HEATER ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

36. ARCHITECTURAL AND STRUCTURAL DETAILS OF ELEVATOR HOUSING, NaK HEATER STACK ROOF FLASHING, HOOD ELEVATION DETAIL. INCLUDES PARTIAL 'BILL OF MATERIAL.' INEEL DRAWING NUMBER 200-0633-00-287-106361. FLUOR NUMBER 5775-CPP-633-A-11. - Idaho National Engineering Laboratory, Old Waste Calcining Facility, Scoville, Butte County, ID

Interfering Effects of Retrieval in Learning New Information

ERIC Educational Resources Information Center

Finn, Bridgid; Roediger, Henry L., III

2013-01-01

In 7 experiments, we explored the role of retrieval in associative updating, that is, in incorporating new information into an associative memory. We tested the hypothesis that retrieval would facilitate incorporating a new contextual detail into a learned association. Participants learned 3 pieces of information--a person's face, name, and…

Concentrating on Affective Feedforward in Online Tutoring

ERIC Educational Resources Information Center

Chen, Ya-Ting; Chou, Yung-Hsin; Cowan, John

2014-01-01

With considerable input from the student voice, the paper centres on a detailed account of the experiences of Western academic, tutoring Eastern students online to develop their critical thinking skills. From their online experiences together as tutor and students, the writers present a considered case for the main emphasis in facilitative online…

The Development of Intrinsic Criteria for Authenticity: A Model for Trust in Naturalistic Researches.

ERIC Educational Resources Information Center

Lincoln, Yvonna S.

This paper presents criteria for establishing the trustworthiness of naturalistic inquiries, and specific techniques to facilitate their achievement or determine the degree of their achievement. The following criteria are briefly described: fairness; and ontological, educative, catalytic and tactical authenticity. Explored in greater detail,…

Facilitating College Students' Recovery through the Use of Collegiate Recovery Programs

ERIC Educational Resources Information Center

DePue, M. Kristina; Hagedorn, W. Bryce

2015-01-01

This article describes an untapped resource that counselors can use to help serve the multiple needs of college students recovering from addiction: collegiate recovery programs. The authors provide detailed information about the collegiate recovery population and give examples of successful programs. Implications for future research are discussed,…

Correlation between ultrasound imaging, cross-sectional anatomy, and histology of the brachial plexus: a review.

PubMed

van Geffen, Geert J; Moayeri, Nizar; Bruhn, Jörgen; Scheffer, Gert J; Chan, Vincent W; Groen, Gerbrand J

2009-01-01

The anatomy of the brachial plexus is complex. To facilitate the understanding of the ultrasound appearance of the brachial plexus, we present a review of important anatomic considerations. A detailed correlation of reconstructed, cross-sectional gross anatomy and histology with ultrasound sonoanatomy is provided.

Listening for Details of Talk: Early Childhood Parent-Teacher Conference Communication Facilitators

ERIC Educational Resources Information Center

Cheatham, Gregory A.; Ostrosky, Michaelene M.

2009-01-01

In this article, the authors present parent-educator conversations, which were selected to illustrate common communication patterns and provide links to some of the Division for Early Childhood of the Council for Exceptional Children's recommended practices for communicating and collaborating with parents. Using conversation analysis, researchers…

National Council on Disability Annual Report. Volume 18, Fiscal Year 1997.

ERIC Educational Resources Information Center

National Council on Disability, Washington, DC.

This annual report details the activities of the National Council on Disability (NCD) in fiscal year 1997. These activities centered on public policy, civil rights, technology, and international policy. In addition, NCD continued its efforts to eliminate government duplication by organizing interagency coordination meetings to facilitate a…

A Bereavement Support Program for Survivors of Cancer Deaths: A Description and Evaluation.

ERIC Educational Resources Information Center

Souter, Susan J.; Moore, Timothy E.

1990-01-01

Describes bereavement support program for survivors of cancer deaths developed by Riverdale Hospital in Toronto, Ontario. Presents detailed program evaluation which asked bereaved survivors who were program participants for one year to evaluate program aspects and facilitation of their grief by volunteers. Recommendations for expansion and…

First Steps to Talking with Families and Staff: Guidelines for Listening Effectively.

ERIC Educational Resources Information Center

Eisenberg, Eileen

2002-01-01

Presents guidelines for child care administrators to become more effective in communicating with families and staff. Suggestions for beginning a dialogue include being visible and accessible, familiar, personable, professional, ethical, and timely. Details procedures for facilitating parent and staff meeting in a confident manner. Reiterates that…

Learning Together and Working Apart: Routines for Organizational Learning in Virtual Teams

ERIC Educational Resources Information Center

Dixon, Nancy

2017-01-01

Purpose: Research suggests that teaming routines facilitate learning in teams. This paper identifies and details how specific teaming routines, implemented in a virtual team, support its continual learning. The study's focus was to generate authentic and descriptive accounts of the interviewees' experiences with virtual teaming routines.…

How to Facilitate Discussions in History

ERIC Educational Resources Information Center

Reisman, Abby

2017-01-01

In this article, Abby Reisman offers four instructional practices that educators can use to help students grapple with history's contradictions and engage in meaningful text-based discussions. Reisman details two suggestions that can be used in history classrooms and across the disciplines: orient students to one another and orient students to the…

Promoting Inquiry through Science Reflective Journal Writing

ERIC Educational Resources Information Center

Towndrow, Phillip Alexander; Ling, Tan Aik; Venthan, A. M.

2008-01-01

The purpose of this research paper is to detail how reflective journal writing can be used to facilitate science students' curiosity and engagement in laboratory work. This study advocates reflective journal writing as an instructional tool and a student-created learning resource that can serve additional formative assessment purposes. The…

BC Jurisdictional Report for CMEC

ERIC Educational Resources Information Center

British Columbia Council on Admissions and Transfer, 2007

2007-01-01

The British Columbia Council on Admissions and Transfer (BCCAT) was established to facilitate admission, articulation and transfer arrangements among British Columbia (BC) post-secondary institutions. Each year BCCAT prepares a detailed work plan and at the end of the fiscal year prepares an Annual Report that summarizes what was achieved. Each…

Delivering Instruction to Adult Learners. Revised Edition.

ERIC Educational Resources Information Center

Cantor, Jeffrey A.

This one-stop guide for trainers and educators of adults in industry, business, or the professions details a results-oriented instructional strategy that is based on the following principles for instructing adults effectively: (1) act as a leader, helper, guide, change agent, coordinator, and facilitator of learning; (2) promote active…

Teaching Diversity through Case Competition

ERIC Educational Resources Information Center

Phillips, T. Nichole; Wood, Lynette I.

2017-01-01

This paper shares the process and outcomes of utilizing case competitions as an approach to diversity education. A university-wide case competition was held for two consecutive years. We detail the procedure for facilitating the competition, the role of internal and external stakeholders, and student performance and feedback. It is our position…

Development of a Palliative Education Assessment Tool for Medical Student Education.

ERIC Educational Resources Information Center

Meekin, Sharon Abele; Klein, Jason E.; Fleischman, Alan R.; Fins, Joseph J.

2000-01-01

Describes the Palliative Education Assessment Tool (PEAT), an innovative assessment to facilitate curricular mapping of palliative care education. The PEAT comprises seven palliative care domains, each of which details specific objectives of knowledge, skills, and attitudes. PEAT enables educators to describe a specific multidimensional aspect of…

StralSV: assessment of sequence variability within similar 3D structures and application to polio RNA-dependent RNA polymerase.

PubMed

Zemla, Adam T; Lang, Dorothy M; Kostova, Tanya; Andino, Raul; Ecale Zhou, Carol L

2011-06-02

Most of the currently used methods for protein function prediction rely on sequence-based comparisons between a query protein and those for which a functional annotation is provided. A serious limitation of sequence similarity-based approaches for identifying residue conservation among proteins is the low confidence in assigning residue-residue correspondences among proteins when the level of sequence identity between the compared proteins is poor. Multiple sequence alignment methods are more satisfactory--still, they cannot provide reliable results at low levels of sequence identity. Our goal in the current work was to develop an algorithm that could help overcome these difficulties by facilitating the identification of structurally (and possibly functionally) relevant residue-residue correspondences between compared protein structures. Here we present StralSV (structure-alignment sequence variability), a new algorithm for detecting closely related structure fragments and quantifying residue frequency from tight local structure alignments. We apply StralSV in a study of the RNA-dependent RNA polymerase of poliovirus, and we demonstrate that the algorithm can be used to determine regions of the protein that are relatively unique, or that share structural similarity with proteins that would be considered distantly related. By quantifying residue frequencies among many residue-residue pairs extracted from local structural alignments, one can infer potential structural or functional importance of specific residues that are determined to be highly conserved or that deviate from a consensus. We further demonstrate that considerable detailed structural and phylogenetic information can be derived from StralSV analyses. StralSV is a new structure-based algorithm for identifying and aligning structure fragments that have similarity to a reference protein. StralSV analysis can be used to quantify residue-residue correspondences and identify residues that may be of particular structural or functional importance, as well as unusual or unexpected residues at a given sequence position. StralSV is provided as a web service at http://proteinmodel.org/AS2TS/STRALSV/.

Building a semantic web-based metadata repository for facilitating detailed clinical modeling in cancer genome studies.

PubMed

Sharma, Deepak K; Solbrig, Harold R; Tao, Cui; Weng, Chunhua; Chute, Christopher G; Jiang, Guoqian

2017-06-05

Detailed Clinical Models (DCMs) have been regarded as the basis for retaining computable meaning when data are exchanged between heterogeneous computer systems. To better support clinical cancer data capturing and reporting, there is an emerging need to develop informatics solutions for standards-based clinical models in cancer study domains. The objective of the study is to develop and evaluate a cancer genome study metadata management system that serves as a key infrastructure in supporting clinical information modeling in cancer genome study domains. We leveraged a Semantic Web-based metadata repository enhanced with both ISO11179 metadata standard and Clinical Information Modeling Initiative (CIMI) Reference Model. We used the common data elements (CDEs) defined in The Cancer Genome Atlas (TCGA) data dictionary, and extracted the metadata of the CDEs using the NCI Cancer Data Standards Repository (caDSR) CDE dataset rendered in the Resource Description Framework (RDF). The ITEM/ITEM_GROUP pattern defined in the latest CIMI Reference Model is used to represent reusable model elements (mini-Archetypes). We produced a metadata repository with 38 clinical cancer genome study domains, comprising a rich collection of mini-Archetype pattern instances. We performed a case study of the domain "clinical pharmaceutical" in the TCGA data dictionary and demonstrated enriched data elements in the metadata repository are very useful in support of building detailed clinical models. Our informatics approach leveraging Semantic Web technologies provides an effective way to build a CIMI-compliant metadata repository that would facilitate the detailed clinical modeling to support use cases beyond TCGA in clinical cancer study domains.

Pre-surgical road map for thyroid cancer and large goiters: Practical benefits of detailed radiological evaluation by surgeon.

PubMed

Panchangam, Ramakanth Bhargav; Guntupalli, Satyam; Seetharamaiah, Thotakura; Kumbhar, Uday Shamrao

2015-01-01

Pre-surgical radiological evaluation of neck is often mandatory for surgical planning in high risk thyroid cancer and large goiters. Frequently, surgeons are overdependent on radiologist's report. In this context, we analysed the practical benefits of surgeon's independent radiological evaluation in our institutional experience. This prospective study was conducted in Endocrine Surgery department of a teaching hospital in South India. Cases operated between January 2011 and June 2012 (18 months) were included. Films of cross-sectional imaging were read in detail by primary and assistant surgeons in correlation with stepwise operative planning and documented. Cases with additional radiological signs on surgeon's evaluation, which were missing in radiologist's report are discussed in detail. F: M ratio is 67:24. Mean age was 45.3 ± 9.8 years (37 - 76). Forty-seven cases of thyroid cancer and 44 cases of large goiters were analysed. Surgeon read additional signs such as obliterated fat plane between goiter and subcutaneous plane; level I lymph nodes; bilateral cervical lymphadenopathy, internal jugular vein thrombus, and pharyngeal invasion helped in pre-operatively planned modification of operative steps for optimal R0 resection and total thyroidectomy. A mean of 1.42 ± 0.83 (1 - 6), additional signs were detected on surgeon's radiological evaluation compared to radiologist's report in 41.7% of cases. These findings modified the pre-operative plan, facilitating better surgical outcome in 28.6% of cases. In high-risk thyroid cancer and large goiters, detailed radiological evaluation by surgeon facilitates optimal surgical resection and superior outcome compared to radiologist report-guided surgery.

Contextual consistency facilitates long-term memory of perceptual detail in barely seen images.

PubMed

Gronau, Nurit; Shachar, Meytal

2015-08-01

It is long known that contextual information affects memory for an object's identity (e.g., its basic level category), yet it is unclear whether schematic knowledge additionally enhances memory for the precise visual appearance of an item. Here we investigated memory for visual detail of merely glimpsed objects. Participants viewed pairs of contextually related and unrelated stimuli, presented for an extremely brief duration (24 ms, masked). They then performed a forced-choice memory-recognition test for the precise perceptual appearance of 1 of 2 objects within each pair (i.e., the "memory-target" item). In 3 experiments, we show that memory-target stimuli originally appearing within contextually related pairs are remembered better than targets appearing within unrelated pairs. These effects are obtained whether the target is presented at test with its counterpart pair object (i.e., when reiterating the original context at encoding) or whether the target is presented alone, implying that the contextual consistency effects are mediated predominantly by processes occurring during stimulus encoding, rather than during stimulus retrieval. Furthermore, visual detail encoding is improved whether object relations involve implied action or not, suggesting that, contrary to some prior suggestions, action is not a necessary component for object-to-object associative "grouping" processes. Our findings suggest that during a brief glimpse, but not under long viewing conditions, contextual associations may play a critical role in reducing stimulus competition for attention selection and in facilitating rapid encoding of sensory details. Theoretical implications with respect to classic frame theories are discussed. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Simulation tools for particle-based reaction-diffusion dynamics in continuous space

PubMed Central

2014-01-01

Particle-based reaction-diffusion algorithms facilitate the modeling of the diffusional motion of individual molecules and the reactions between them in cellular environments. A physically realistic model, depending on the system at hand and the questions asked, would require different levels of modeling detail such as particle diffusion, geometrical confinement, particle volume exclusion or particle-particle interaction potentials. Higher levels of detail usually correspond to increased number of parameters and higher computational cost. Certain systems however, require these investments to be modeled adequately. Here we present a review on the current field of particle-based reaction-diffusion software packages operating on continuous space. Four nested levels of modeling detail are identified that capture incrementing amount of detail. Their applicability to different biological questions is discussed, arching from straight diffusion simulations to sophisticated and expensive models that bridge towards coarse grained molecular dynamics. PMID:25737778

SCOWLP classification: Structural comparison and analysis of protein binding regions

PubMed Central

Teyra, Joan; Paszkowski-Rogacz, Maciej; Anders, Gerd; Pisabarro, M Teresa

2008-01-01

Background Detailed information about protein interactions is critical for our understanding of the principles governing protein recognition mechanisms. The structures of many proteins have been experimentally determined in complex with different ligands bound either in the same or different binding regions. Thus, the structural interactome requires the development of tools to classify protein binding regions. A proper classification may provide a general view of the regions that a protein uses to bind others and also facilitate a detailed comparative analysis of the interacting information for specific protein binding regions at atomic level. Such classification might be of potential use for deciphering protein interaction networks, understanding protein function, rational engineering and design. Description Protein binding regions (PBRs) might be ideally described as well-defined separated regions that share no interacting residues one another. However, PBRs are often irregular, discontinuous and can share a wide range of interacting residues among them. The criteria to define an individual binding region can be often arbitrary and may differ from other binding regions within a protein family. Therefore, the rational behind protein interface classification should aim to fulfil the requirements of the analysis to be performed. We extract detailed interaction information of protein domains, peptides and interfacial solvent from the SCOWLP database and we classify the PBRs of each domain family. For this purpose, we define a similarity index based on the overlapping of interacting residues mapped in pair-wise structural alignments. We perform our classification with agglomerative hierarchical clustering using the complete-linkage method. Our classification is calculated at different similarity cut-offs to allow flexibility in the analysis of PBRs, feature especially interesting for those protein families with conflictive binding regions. The hierarchical classification of PBRs is implemented into the SCOWLP database and extends the SCOP classification with three additional family sub-levels: Binding Region, Interface and Contacting Domains. SCOWLP contains 9,334 binding regions distributed within 2,561 families. In 65% of the cases we observe families containing more than one binding region. Besides, 22% of the regions are forming complex with more than one different protein family. Conclusion The current SCOWLP classification and its web application represent a framework for the study of protein interfaces and comparative analysis of protein family binding regions. This comparison can be performed at atomic level and allows the user to study interactome conservation and variability. The new SCOWLP classification may be of great utility for reconstruction of protein complexes, understanding protein networks and ligand design. SCOWLP will be updated with every SCOP release. The web application is available at . PMID:18182098

Structural Changes Due to Antagonist Binding in Ligand Binding Pocket of Androgen Receptor Elucidated Through Molecular Dynamics Simulations.

PubMed

Sakkiah, Sugunadevi; Kusko, Rebecca; Pan, Bohu; Guo, Wenjing; Ge, Weigong; Tong, Weida; Hong, Huixiao

2018-01-01

When a small molecule binds to the androgen receptor (AR), a conformational change can occur which impacts subsequent binding of co-regulator proteins and DNA. In order to accurately study this mechanism, the scientific community needs a crystal structure of the Wild type AR (WT-AR) ligand binding domain, bound with antagonist. To address this open need, we leveraged molecular docking and molecular dynamics (MD) simulations to construct a structure of the WT-AR ligand binding domain bound with antagonist bicalutamide. The structure of mutant AR (Mut-AR) bound with this same antagonist informed this study. After molecular docking analysis pinpointed the suitable binding orientation of a ligand in AR, the model was further optimized through 1 μs of MD simulations. Using this approach, three molecular systems were studied: (1) WT-AR bound with agonist R1881, (2) WT-AR bound with antagonist bicalutamide, and (3) Mut-AR bound with bicalutamide. Our structures were very similar to the experimentally determined structures of both WT-AR with R1881 and Mut-AR with bicalutamide, demonstrating the trustworthiness of this approach. In our model, when WT-AR is bound with bicalutamide, Val716/Lys720/Gln733, or Met734/Gln738/Glu897 move and thus disturb the positive and negative charge clumps of the AF2 site. This disruption of the AF2 site is key for understanding the impact of antagonist binding on subsequent co-regulator binding. In conclusion, the antagonist induced structural changes in WT-AR detailed in this study will enable further AR research and will facilitate AR targeting drug discovery.

Automated Quantification of Arbitrary Arm-Segment Structure in Spiral Galaxies

NASA Astrophysics Data System (ADS)

Davis, Darren Robert

This thesis describes a system that, given approximately-centered images of spiral galaxies, produces quantitative descriptions of spiral galaxy structure without the need for per-image human input. This structure information consists of a list of spiral arm segments, each associated with a fitted logarithmic spiral arc and a pixel region. This list-of-arcs representation allows description of arbitrary spiral galaxy structure: the arms do not need to be symmetric, may have forks or bends, and, more generally, may be arranged in any manner with a consistent spiral-pattern center (non-merging galaxies have a sufficiently well-defined center). Such flexibility is important in order to accommodate the myriad structure variations observed in spiral galaxies. From the arcs produced from our method it is possible to calculate measures of spiral galaxy structure such as winding direction, winding tightness, arm counts, asymmetry, or other values of interest (including user-defined measures). In addition to providing information about the spiral arm "skeleton" of each galaxy, our method can enable analyses of brightness within individual spiral arms, since we provide the pixel regions associated with each spiral arm segment. For winding direction, arm tightness, and arm count, comparable information is available (to various extents) from previous efforts; to the extent that such information is available, we find strong correspondence with our output. We also characterize the changes to (and invariances in) our output as a function of modifications to important algorithm parameters. By enabling generation of extensive data about spiral galaxy structure from large-scale sky surveys, our method will enable new discoveries and tests regarding the nature of galaxies and the universe, and will facilitate subsequent work to automatically fit detailed brightness models of spiral galaxies.

Structure of HIV-1 gp120 with gp41-interactive region reveals layered envelope architecture and basis of conformational mobility

PubMed Central

Pancera, Marie; Majeed, Shahzad; Ban, Yih-En Andrew; Chen, Lei; Huang, Chih-chin; Kong, Leopold; Stuckey, Jonathan; Zhou, Tongqing; Robinson, James E.; Schief, William R.; Sodroski, Joseph; Wyatt, Richard; Kwong, Peter D.

2009-01-01

The viral spike of HIV-1 is composed of three gp120 envelope glycoproteins attached noncovalently to three gp41 transmembrane molecules. Viral entry is initiated by binding to the CD4 receptor on the cell surface, which induces large conformational changes in gp120. These changes not only provide a model for receptor-triggered entry, but affect spike sensitivity to drug- and antibody-mediated neutralization. Although some of the details of the CD4-induced conformational change have been visualized by crystal structures and cryoelectron tomograms, the critical gp41-interactive region of gp120 was missing from previous atomic-level characterizations. Here we determine the crystal structure of an HIV-1 gp120 core with intact gp41-interactive region in its CD4-bound state, compare this structure to unliganded and antibody-bound forms to identify structurally invariant and plastic components, and use ligand-oriented cryoelectron tomograms to define component mobility in the viral spike context. Newly defined gp120 elements proximal to the gp41 interface complete a 7-stranded β-sandwich, which appeared invariant in conformation. Loop excursions emanating from the sandwich form three topologically separate—and structurally plastic—layers, topped off by the highly glycosylated gp120 outer domain. Crystal structures, cryoelectron tomograms, and interlayer chemistry were consistent with a mechanism in which the layers act as a shape-changing spacer, facilitating movement between outer domain and gp41-associated β-sandwich and providing for conformational diversity used in immune evasion. A “layered” gp120 architecture thus allows movement among alternative glycoprotein conformations required for virus entry and immune evasion, whereas a β-sandwich clamp maintains gp120–gp41 interaction and regulates gp41 transitions. PMID:20080564

Structure of HIV-1 gp120 with gp41-interactive region reveals layered envelope architecture and basis of conformational mobility.

PubMed

Pancera, Marie; Majeed, Shahzad; Ban, Yih-En Andrew; Chen, Lei; Huang, Chih-chin; Kong, Leopold; Kwon, Young Do; Stuckey, Jonathan; Zhou, Tongqing; Robinson, James E; Schief, William R; Sodroski, Joseph; Wyatt, Richard; Kwong, Peter D

2010-01-19

The viral spike of HIV-1 is composed of three gp120 envelope glycoproteins attached noncovalently to three gp41 transmembrane molecules. Viral entry is initiated by binding to the CD4 receptor on the cell surface, which induces large conformational changes in gp120. These changes not only provide a model for receptor-triggered entry, but affect spike sensitivity to drug- and antibody-mediated neutralization. Although some of the details of the CD4-induced conformational change have been visualized by crystal structures and cryoelectron tomograms, the critical gp41-interactive region of gp120 was missing from previous atomic-level characterizations. Here we determine the crystal structure of an HIV-1 gp120 core with intact gp41-interactive region in its CD4-bound state, compare this structure to unliganded and antibody-bound forms to identify structurally invariant and plastic components, and use ligand-oriented cryoelectron tomograms to define component mobility in the viral spike context. Newly defined gp120 elements proximal to the gp41 interface complete a 7-stranded beta-sandwich, which appeared invariant in conformation. Loop excursions emanating from the sandwich form three topologically separate--and structurally plastic--layers, topped off by the highly glycosylated gp120 outer domain. Crystal structures, cryoelectron tomograms, and interlayer chemistry were consistent with a mechanism in which the layers act as a shape-changing spacer, facilitating movement between outer domain and gp41-associated beta-sandwich and providing for conformational diversity used in immune evasion. A "layered" gp120 architecture thus allows movement among alternative glycoprotein conformations required for virus entry and immune evasion, whereas a beta-sandwich clamp maintains gp120-gp41 interaction and regulates gp41 transitions.

Structural details below roadway, looking north from south abutment. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Structural details below roadway, looking north from south abutment. - Pleasantville Covered Bridge, Spanning Little Manatawny Creek at Covered Bridge Road (State Route 1030), Manatawny, Berks County, PA

Active Site Hydrophobicity and the Convergent Evolution of Paraoxonase Activity in Structurally Divergent Enzymes: The Case of Serum Paraoxonase 1

PubMed Central

2016-01-01

Serum paraoxonase 1 (PON1) is a native lactonase capable of promiscuously hydrolyzing a broad range of substrates, including organophosphates, esters, and carbonates. Structurally, PON1 is a six-bladed β-propeller with a flexible loop (residues 70–81) covering the active site. This loop contains a functionally critical Tyr at position 71. We have performed detailed experimental and computational analyses of the role of selected Y71 variants in the active site stability and catalytic activity in order to probe the role of Y71 in PON1’s lactonase and organophosphatase activities. We demonstrate that the impact of Y71 substitutions on PON1’s lactonase activity is minimal, whereas the kcat for the paraoxonase activity is negatively perturbed by up to 100-fold, suggesting greater mutational robustness of the native activity. Additionally, while these substitutions modulate PON1’s active site shape, volume, and loop flexibility, their largest effect is in altering the solvent accessibility of the active site by expanding the active site volume, allowing additional water molecules to enter. This effect is markedly more pronounced in the organophosphatase activity than the lactonase activity. Finally, a detailed comparison of PON1 to other organophosphatases demonstrates that either a similar “gating loop” or a highly buried solvent-excluding active site is a common feature of these enzymes. We therefore posit that modulating the active site hydrophobicity is a key element in facilitating the evolution of organophosphatase activity. This provides a concrete feature that can be utilized in the rational design of next-generation organophosphate hydrolases that are capable of selecting a specific reaction from a pool of viable substrates. PMID:28026940

Active Site Hydrophobicity and the Convergent Evolution of Paraoxonase Activity in Structurally Divergent Enzymes: The Case of Serum Paraoxonase 1.

PubMed

Blaha-Nelson, David; Krüger, Dennis M; Szeler, Klaudia; Ben-David, Moshe; Kamerlin, Shina Caroline Lynn

2017-01-25

Serum paraoxonase 1 (PON1) is a native lactonase capable of promiscuously hydrolyzing a broad range of substrates, including organophosphates, esters, and carbonates. Structurally, PON1 is a six-bladed β-propeller with a flexible loop (residues 70-81) covering the active site. This loop contains a functionally critical Tyr at position 71. We have performed detailed experimental and computational analyses of the role of selected Y71 variants in the active site stability and catalytic activity in order to probe the role of Y71 in PON1's lactonase and organophosphatase activities. We demonstrate that the impact of Y71 substitutions on PON1's lactonase activity is minimal, whereas the k cat for the paraoxonase activity is negatively perturbed by up to 100-fold, suggesting greater mutational robustness of the native activity. Additionally, while these substitutions modulate PON1's active site shape, volume, and loop flexibility, their largest effect is in altering the solvent accessibility of the active site by expanding the active site volume, allowing additional water molecules to enter. This effect is markedly more pronounced in the organophosphatase activity than the lactonase activity. Finally, a detailed comparison of PON1 to other organophosphatases demonstrates that either a similar "gating loop" or a highly buried solvent-excluding active site is a common feature of these enzymes. We therefore posit that modulating the active site hydrophobicity is a key element in facilitating the evolution of organophosphatase activity. This provides a concrete feature that can be utilized in the rational design of next-generation organophosphate hydrolases that are capable of selecting a specific reaction from a pool of viable substrates.

Photochemical Alternation of Phragmites australis Plant Litter: New Insight into the Chemical Evolution of Particulate Organic Matter

NASA Astrophysics Data System (ADS)

Carrasquillo, A. J.; Gelfond, C. E.; Kocar, B. D.

2015-12-01

The photolysis of natural organic matter (NOM) is a potential pathway for the alteration of material that is not easily biodegraded. Irradiation can alter the physical state of organic matter by facilitating the cycling between the particulate (POM) and dissolved (DOM) pools. However, a detailed understanding of the underlying chemical changes to the material in both phases is lacking. Here, we use a suspension of particles derived from Phragmites australis, a common marsh reed with high lignin content, as our model "recalcitrant" POM substrate. The solution was irradiated for three weeks with regular sampling, and the composition of the POM and the photo-produced DOM were measured separately using a suite of mass spectrometric and spectroscopic techniques. The chemical composition of individual molecules was measured by coupling soft ionization techniques (electrospray (ESI) and matrix assisted laser desorption (MALDI) to high-resolution mass spectrometry. Structural information, including the distribution of the major carbon containing functional groups, was obtained using a combination of FTIR for bulk analyses and scanning transmission x-ray microscopy (STXM) for spatially resolved chemistry. Results are discussed in the context of differences in chemical composition and structure with increased irradiation time for both organic matter pools. We observed a general shift in the mass spectra of POM towards lower molecular weight masses and an increase in the abundance of ions in DOM as a function of irradiation time- hence the larger POM matrix is likely fragmenting into smaller species that are more soluble. Spectroscopic measurements indicate that the abundance of acidic and alcohol functionalities increased with irradiation in both carbon pools. These complementary approaches provide new detailed information about how the chemical composition of recalcitrant NOM evolves as it is exposed to sunlight.

Detailed seismic velocity of the incoming subducting sediments in the 2004 great Sumatra earthquake rupture zone from full waveform inversion of long offset seismic data

NASA Astrophysics Data System (ADS)

Qin, Yanfang; Singh, Satish C.

2017-04-01

The nature of incoming sediments defines the locking mechanism on the megathrust, and the development and evolution of the accretionary wedge. Here we present results from seismic full waveform inversion of 12 km long offset seismic reflection data within the trench in the 2004 Sumatra earthquake rupture zone area that provide detailed quantitative information on the incoming oceanic sediments and the trench-fill sediments. The thickness of sediments in this area is 3-4 km, and P wave velocity is as much as 4.5 km/s just above the oceanic crust, suggesting the presence of silica-rich highly compacted and lithified sediments leading to a strong coupling up to the subduction front. We also find an 70-80 m thick low-velocity layer, capped by a high-velocity layer, at 0.8 km above the subducting plate. This low-velocity layer, previously identified as high-amplitude negative polarity reflection, could have porosity of up to 30% containing overpressured fluids, which could act as a protodécollement seaward from the accretionary prism and décollement beneath the forearc. This weak protodécollement combined with the high-velocity indurated sediments above the basement possibly facilitated the rupture propagating up to the front during the 2004 earthquake and enhancing the tsunami. We also find another low-velocity layer within the sediments that may act as a secondary décollement observed offshore central Sumatra, forming bivergent pop-up structures and acting as a conveyer belt in preserving these pop-up structures in the forearc region.

Educational implications for surgical telementoring: a current review with recommendations for future practice, policy, and research.

PubMed

Augestad, K M; Han, H; Paige, J; Ponsky, T; Schlachta, C M; Dunkin, B; Mellinger, J

2017-10-01

Surgical telementoring (ST) was introduced in the sixties, promoting videoconferencing to enhance surgical education across large distances. Widespread use of ST in the surgical community is lacking. Despite numerous surveys assessing ST, there remains a lack of high-level scientific evidence demonstrating its impact on mentorship and surgical education. Despite this, there is an ongoing paradigm shift involving remote presence technologies and their application to skill development and technique dissemination in the international surgical community. Factors facilitating this include improved access to ST technology, including ease of use and data transmission, and affordability. Several international research initiatives have commenced to strengthen the scientific foundation documenting the impact of ST in surgical education and performance. International experts on ST were invited to the SAGES Project Six Summit in August 2015. Two experts in surgical education prepared relevant questions for discussion and organized the meeting (JP and HH). The questions were open-ended, and the discussion continued until no new item appeared. The transcripts of interviews were recorded by a secretary from SAGES. In this paper, we present a summary of the work performed by the SAGES Project 6 Education Working Group. We summarize the existing evidence regarding education in ST, identify and detail conceptual educational frameworks that may be used during ST, and present a structured framework for an educational curriculum in ST. The educational impact and optimal curricular organization of ST programs are largely unexplored. We outline the critical components of a structured ST curriculum, including prerequisites, teaching modalities, and key curricular components. We also detail research strategies critical to its continued evolution as an educational tool, including randomized controlled trials, establishment of a quality registry, qualitative research, learning analytics, and development of a standardized taxonomy.

MODFLOW-2005 : the U.S. Geological Survey modular ground-water model--the ground-water flow process

USGS Publications Warehouse

Harbaugh, Arlen W.

2005-01-01

This report presents MODFLOW-2005, which is a new version of the finite-difference ground-water model commonly called MODFLOW. Ground-water flow is simulated using a block-centered finite-difference approach. Layers can be simulated as confined or unconfined. Flow associated with external stresses, such as wells, areal recharge, evapotranspiration, drains, and rivers, also can be simulated. The report includes detailed explanations of physical and mathematical concepts on which the model is based, an explanation of how those concepts are incorporated in the modular structure of the computer program, instructions for using the model, and details of the computer code. The modular structure consists of a MAIN Program and a series of highly independent subroutines. The subroutines are grouped into 'packages.' Each package deals with a specific feature of the hydrologic system that is to be simulated, such as flow from rivers or flow into drains, or with a specific method of solving the set of simultaneous equations resulting from the finite-difference method. Several solution methods are incorporated, including the Preconditioned Conjugate-Gradient method. The division of the program into packages permits the user to examine specific hydrologic features of the model independently. This also facilitates development of additional capabilities because new packages can be added to the program without modifying the existing packages. The input and output systems of the computer program also are designed to permit maximum flexibility. The program is designed to allow other capabilities, such as transport and optimization, to be incorporated, but this report is limited to describing the ground-water flow capability. The program is written in Fortran 90 and will run without modification on most computers that have a Fortran 90 compiler.

Going beyond the identification of change facilitators to effectively implement a new model of services: lessons learned from a case example in paediatric rehabilitation.

PubMed

Camden, Chantal; Swaine, Bonnie; Tétreault, Sylvie; Carrière, Monique

2011-01-01

To identify facilitators and barriers to service reorganization, how they evolved and interacted to influence change during the implementation of a new service delivery model of paediatric rehabilitation. Over 3 years, different stakeholders responded to SWOT questionnaires (n = 139) and participated in focus groups (n = 19) and telephone interviews (n = 13). A framework based on socio constructivist theories made sense of the data. Facilitators related to the programme's structure (e.g. funding), the actors (e.g. willingness to test the new service model) and the change management process (e.g. participative approach). Some initial facilitators became barriers (e.g. leadership lacked at the end), while other barriers emerged (e.g. lack of tools). Understanding factor interactions requires examining the multiple actors' intentions, actions and consequences and their relations with structural elements. Analysing facilitators and barriers helped better understand the change processes, but this must be followed by concrete actions to successfully implement new paediatric rehabilitation models.

View northeast; interior structural detail Naval Base PhiladelphiaPhiladelphia Naval ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

View northeast; interior structural detail - Naval Base Philadelphia-Philadelphia Naval Shipyard, Foundry-Propeller Shop, North of Porter Avenue, west of Third Street West, Philadelphia, Philadelphia County, PA

Prolonged rote learning produces delayed memory facilitation and metabolic changes in the hippocampus of the ageing human brain.

PubMed

Roche, Richard Ap; Mullally, Sinéad L; McNulty, Jonathan P; Hayden, Judy; Brennan, Paul; Doherty, Colin P; Fitzsimons, Mary; McMackin, Deirdre; Prendergast, Julie; Sukumaran, Sunita; Mangaoang, Maeve A; Robertson, Ian H; O'Mara, Shane M

2009-11-20

Repeated rehearsal is one method by which verbal material may be transferred from short- to long-term memory. We hypothesised that extended engagement of memory structures through prolonged rehearsal would result in enhanced efficacy of recall and also of brain structures implicated in new learning. Twenty-four normal participants aged 55-70 (mean = 60.1) engaged in six weeks of rote learning, during which they learned 500 words per week every week (prose, poetry etc.). An extensive battery of memory tests was administered on three occasions, each six weeks apart. In addition, proton magnetic resonance spectroscopy (1H-MRS) was used to measure metabolite levels in seven voxels of interest (VOIs) (including hippocampus) before and after learning. Results indicate a facilitation of new learning that was evident six weeks after rote learning ceased. This facilitation occurred for verbal/episodic material only, and was mirrored by a metabolic change in left posterior hippocampus, specifically an increase in NAA/(Cr+Cho) ratio. Results suggest that repeated activation of memory structures facilitates anamnesis and may promote neuronal plasticity in the ageing brain, and that compliance is a key factor in such facilitation as the effect was confined to those who engaged fully with the training.

Limited-angle multi-energy CT using joint clustering prior and sparsity regularization

NASA Astrophysics Data System (ADS)

Zhang, Huayu; Xing, Yuxiang

2016-03-01

In this article, we present an easy-to-implement Multi-energy CT scanning strategy and a corresponding reconstruction method, which facilitate spectral CT imaging by improving the data efficiency the number-of-energy- channel fold without introducing visible limited-angle artifacts caused by reducing projection views. Leveraging the structure coherence at different energies, we first pre-reconstruct a prior structure information image using projection data from all energy channels. Then, we perform a k-means clustering on the prior image to generate a sparse dictionary representation for the image, which severs as a structure information constraint. We com- bine this constraint with conventional compressed sensing method and proposed a new model which we referred as Joint Clustering Prior and Sparsity Regularization (CPSR). CPSR is a convex problem and we solve it by Alternating Direction Method of Multipliers (ADMM). We verify our CPSR reconstruction method with a numerical simulation experiment. A dental phantom with complicate structures of teeth and soft tissues is used. X-ray beams from three spectra of different peak energies (120kVp, 90kVp, 60kVp) irradiate the phantom to form tri-energy projections. Projection data covering only 75◦ from each energy spectrum are collected for reconstruction. Independent reconstruction for each energy will cause severe limited-angle artifacts even with the help of compressed sensing approaches. Our CPSR provides us with images free of the limited-angle artifact. All edge details are well preserved in our experimental study.

The Integrin Receptor in Biologically Relevant Bilayers: Insights from Molecular Dynamics Simulations.

PubMed

Kalli, Antreas C; Rog, Tomasz; Vattulainen, Ilpo; Campbell, Iain D; Sansom, Mark S P

2017-08-01

Integrins are heterodimeric (αβ) cell surface receptors that are potential therapeutic targets for a number of diseases. Despite the existence of structural data for all parts of integrins, the structure of the complete integrin receptor is still not available. We have used available structural data to construct a model of the complete integrin receptor in complex with talin F2-F3 domain. It has been shown that the interactions of integrins with their lipid environment are crucial for their function but details of the integrin/lipid interactions remain elusive. In this study an integrin/talin complex was inserted in biologically relevant bilayers that resemble the cell plasma membrane containing zwitterionic and charged phospholipids, cholesterol and sphingolipids to study the dynamics of the integrin receptor and its effect on bilayer structure and dynamics. The results of this study demonstrate the dynamic nature of the integrin receptor and suggest that the presence of the integrin receptor alters the lipid organization between the two leaflets of the bilayer. In particular, our results suggest elevated density of cholesterol and of phosphatidylserine lipids around the integrin/talin complex and a slowing down of lipids in an annulus of ~30 Å around the protein due to interactions between the lipids and the integrin/talin F2-F3 complex. This may in part regulate the interactions of integrins with other related proteins or integrin clustering thus facilitating signal transduction across cell membranes.

Technology-enabled academic detailing: computer-mediated education between pharmacists and physicians for evidence-based prescribing.

PubMed

Ho, Kendall; Nguyen, Anne; Jarvis-Selinger, Sandra; Novak Lauscher, Helen; Cressman, Céline; Zibrik, Lindsay

2013-09-01

Academic detailing (AD) is the practice of specially trained pharmacists with detailed medication knowledge meeting with physicians to share best practices of prescribing. AD has demonstrated efficacy in positively influencing physicians' prescribing behavior. Nevertheless, a key challenge has been that physicians in rural and remote locations, or physicians who are time challenged, have limited ability to participate in face-to-face meetings with academic detailers, as these specially trained academic detailers are primarily urban-based and limited in numbers. To determine the feasibility of using information technologies to facilitate communication between academic detailers and physicians (known as Technology-Enabled Academic Detailing or TEAD) through a comparison to traditional face-to-face academic detailing (AD). Specifically, TEAD is compared to AD in terms of the ability to aid physicians in acquiring evidence-informed prescribing information on diabetes-related medications, measured in terms of time efficiency, satisfaction of both physicians and pharmacists, and quality of knowledge exchange. General Practitioner Physicians (n=105) and pharmacists (n=12) were recruited from across British Columbia. Pharmacists were trained to be academic detailers on diabetes medication usage. Physicians were assigned to one of four intervention groups to receive four academic detailing sessions from trained pharmacists. Intervention groups included: (1) AD only, (2) TEAD only, (3) TEAD crossed over to AD at midpoint, and (4) AD crossed over to TEAD at midpoint. Evaluation included physician-completed surveys before and after each session, pharmacist logs after each detailing session, interviews and focus groups with physicians and pharmacists at study completion, as well as a technical support log to record all phone calls and emails from physicians and pharmacists regarding any technical challenges during the TEAD sessions, or usage of the web portal. Because recruitment was very low for the cross over groups, we analyzed the results in two groups instead: AD only and TEAD only. 354 sessions were conducted (AD=161, TEAD=193). Of these, complete data were available for 300 sessions, which were included in analysis (AD=133, TEAD=167). On average, TEAD sessions were 49min long, and AD sessions 81min long. Overall, physicians enjoyed both modalities of academic detailing (AD and TEAD) because they received information that both reinforced their existing diabetes knowledge and also provided new prescribing insights and approaches. The results suggest that TEAD is an acceptable alternative to AD for providing physicians advice about prescribing. TEAD is more time efficient, facilitates effective knowledge exchange and interprofessional collaboration, and can reach those physicians virtually where face-to-face AD is not possible or practical. Due to logistics, physicians were allocated, rather than randomized, to receive AD and/or TEAD. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Marguerite Arnet Residence, exterior roof structure detail, looking northwest. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Marguerite Arnet Residence, exterior roof structure detail, looking northwest. - Adam & Bessie Arnet Homestead, Marguerite Arnet Residence, 560 feet northeast of Adam & Bessie Arnet Residence, Model, Las Animas County, CO

32. LOWER CHORD / FLOOR STRUCTURE DETAIL OF THROUGH TRUSS. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

32. LOWER CHORD / FLOOR STRUCTURE DETAIL OF THROUGH TRUSS. VIEW TO NORTH. - Abraham Lincoln Memorial Bridge, Spanning Missouri River on Highway 30 between Nebraska & Iowa, Blair, Washington County, NE

31. LOWER CHORD / FLOOR STRUCTURE DETAIL OF THROUGH TRUSS. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

31. LOWER CHORD / FLOOR STRUCTURE DETAIL OF THROUGH TRUSS. VIEW TO NORTH. - Abraham Lincoln Memorial Bridge, Spanning Missouri River on Highway 30 between Nebraska & Iowa, Blair, Washington County, NE

More Than One Way to Debrief: A Critical Review of Healthcare Simulation Debriefing Methods.

PubMed

Sawyer, Taylor; Eppich, Walter; Brett-Fleegler, Marisa; Grant, Vincent; Cheng, Adam

2016-06-01

Debriefing is a critical component in the process of learning through healthcare simulation. This critical review examines the timing, facilitation, conversational structures, and process elements used in healthcare simulation debriefing. Debriefing occurs either after (postevent) or during (within-event) the simulation. The debriefing conversation can be guided by either a facilitator (facilitator-guided) or the simulation participants themselves (self-guided). Postevent facilitator-guided debriefing may incorporate several conversational structures. These conversational structures break the debriefing discussion into a series of 3 or more phases to help organize the debriefing and ensure the conversation proceeds in an orderly manner. Debriefing process elements are an array of techniques to optimize reflective experience and maximize the impact of debriefing. These are divided here into the following 3 categories: essential elements, conversational techniques/educational strategies, and debriefing adjuncts. This review provides both novice and advanced simulation educators with an overview of various methods of conducting healthcare simulation debriefing. Future research will investigate which debriefing methods are best for which contexts and for whom, and also explore how lessons from simulation debriefing translate to debriefing in clinical practice.

Enhancements to the SHARP Build System and NEK5000 Coupling

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

McCaskey, Alex; Bennett, Andrew R.; Billings, Jay Jay

The SHARP project for the Department of Energy's Nuclear Energy Advanced Modeling and Simulation (NEAMS) program provides a multiphysics framework for coupled simulations of advanced nuclear reactor designs. It provides an overall coupling environment that utilizes custom interfaces to couple existing physics codes through a common spatial decomposition and unique solution transfer component. As of this writing, SHARP couples neutronics, thermal hydraulics, and structural mechanics using PROTEUS, Nek5000, and Diablo respectively. This report details two primary SHARP improvements regarding the Nek5000 and Diablo individual physics codes: (1) an improved Nek5000 coupling interface that lets SHARP achieve a vast increase inmore » overall solution accuracy by manipulating the structure of the internal Nek5000 spatial mesh, and (2) the capability to seamlessly couple structural mechanics calculations into the framework through improvements to the SHARP build system. The Nek5000 coupling interface now uses a barycentric Lagrange interpolation method that takes the vertex-based power and density computed from the PROTEUS neutronics solver and maps it to the user-specified, general-order Nek5000 spectral element mesh. Before this work, SHARP handled this vertex-based solution transfer in an averaging-based manner. SHARP users can now achieve higher levels of accuracy by specifying any arbitrary Nek5000 spectral mesh order. This improvement takes the average percentage error between the PROTEUS power solution and the Nek5000 interpolated result down drastically from over 23 % to just above 2 %, and maintains the correct power profile. We have integrated Diablo into the SHARP build system to facilitate the future coupling of structural mechanics calculations into SHARP. Previously, simulations involving Diablo were done in an iterative manner, requiring a large amount manual work, and left only as a task for advanced users. This report will detail a new Diablo build system that was implemented using GNU Autotools, mirroring much of the current SHARP build system, and easing the use of structural mechanics calculations for end-users of the SHARP multiphysics framework. It lets users easily build and use Diablo as a stand-alone simulation, as well as fully couple with the other SHARP physics modules. The top-level SHARP build system was modified to allow Diablo to hook in directly. New dependency handlers were implemented to let SHARP users easily build the framework with these new simulation capabilities. The remainder of this report will describe this work in full, with a detailed discussion of the overall design philosophy of SHARP, the new solution interpolation method introduced, and the Diablo integration work. We will conclude with a discussion of possible future SHARP improvements that will serve to increase solution accuracy and framework capability.« less

Structural interpretation of El Hierro (Canary Islands) rifts system from gravity inversion modelling

NASA Astrophysics Data System (ADS)

Sainz-Maza, S.; Montesinos, F. G.; Martí, J.; Arnoso, J.; Calvo, M.; Borreguero, A.

2017-08-01

Recent volcanism in El Hierro Island is mostly concentrated along three elongated and narrow zones which converge at the center of the island. These zones with extensive volcanism have been identified as rift zones. The presence of similar structures is common in many volcanic oceanic islands, so understanding their origin, dynamics and structure is important to conduct hazard assessment in such environments. There is still not consensus on the origin of the El Hierro rift zones, having been associated with mantle uplift or interpreted as resulting from gravitational spreading and flank instability. To further understand the internal structure and origin of the El Hierro rift systems, starting from the previous gravity studies, we developed a new 3D gravity inversion model for its shallower layers, gathering a detailed picture of this part of the island, which has permitted a new interpretation about these rifts. Previous models already identified a main central magma accumulation zone and several shallower high density bodies. The new model allows a better resolution of the pathways that connect both levels and the surface. Our results do not point to any correspondence between the upper parts of these pathways and the rift identified at the surface. Non-clear evidence of progression toward deeper parts into the volcanic system is shown, so we interpret them as very shallow structures, probably originated by local extensional stresses derived from gravitational loading and flank instability, which are used to facilitate the lateral transport of magma when it arrives close to the surface.

CAVER 3.0: A Tool for the Analysis of Transport Pathways in Dynamic Protein Structures

PubMed Central

Strnad, Ondrej; Brezovsky, Jan; Kozlikova, Barbora; Gora, Artur; Sustr, Vilem; Klvana, Martin; Medek, Petr; Biedermannova, Lada; Sochor, Jiri; Damborsky, Jiri

2012-01-01

Tunnels and channels facilitate the transport of small molecules, ions and water solvent in a large variety of proteins. Characteristics of individual transport pathways, including their geometry, physico-chemical properties and dynamics are instrumental for understanding of structure-function relationships of these proteins, for the design of new inhibitors and construction of improved biocatalysts. CAVER is a software tool widely used for the identification and characterization of transport pathways in static macromolecular structures. Herein we present a new version of CAVER enabling automatic analysis of tunnels and channels in large ensembles of protein conformations. CAVER 3.0 implements new algorithms for the calculation and clustering of pathways. A trajectory from a molecular dynamics simulation serves as the typical input, while detailed characteristics and summary statistics of the time evolution of individual pathways are provided in the outputs. To illustrate the capabilities of CAVER 3.0, the tool was applied for the analysis of molecular dynamics simulation of the microbial enzyme haloalkane dehalogenase DhaA. CAVER 3.0 safely identified and reliably estimated the importance of all previously published DhaA tunnels, including the tunnels closed in DhaA crystal structures. Obtained results clearly demonstrate that analysis of molecular dynamics simulation is essential for the estimation of pathway characteristics and elucidation of the structural basis of the tunnel gating. CAVER 3.0 paves the way for the study of important biochemical phenomena in the area of molecular transport, molecular recognition and enzymatic catalysis. The software is freely available as a multiplatform command-line application at http://www.caver.cz. PMID:23093919

CAVER 3.0: a tool for the analysis of transport pathways in dynamic protein structures.

PubMed

Chovancova, Eva; Pavelka, Antonin; Benes, Petr; Strnad, Ondrej; Brezovsky, Jan; Kozlikova, Barbora; Gora, Artur; Sustr, Vilem; Klvana, Martin; Medek, Petr; Biedermannova, Lada; Sochor, Jiri; Damborsky, Jiri

2012-01-01

Tunnels and channels facilitate the transport of small molecules, ions and water solvent in a large variety of proteins. Characteristics of individual transport pathways, including their geometry, physico-chemical properties and dynamics are instrumental for understanding of structure-function relationships of these proteins, for the design of new inhibitors and construction of improved biocatalysts. CAVER is a software tool widely used for the identification and characterization of transport pathways in static macromolecular structures. Herein we present a new version of CAVER enabling automatic analysis of tunnels and channels in large ensembles of protein conformations. CAVER 3.0 implements new algorithms for the calculation and clustering of pathways. A trajectory from a molecular dynamics simulation serves as the typical input, while detailed characteristics and summary statistics of the time evolution of individual pathways are provided in the outputs. To illustrate the capabilities of CAVER 3.0, the tool was applied for the analysis of molecular dynamics simulation of the microbial enzyme haloalkane dehalogenase DhaA. CAVER 3.0 safely identified and reliably estimated the importance of all previously published DhaA tunnels, including the tunnels closed in DhaA crystal structures. Obtained results clearly demonstrate that analysis of molecular dynamics simulation is essential for the estimation of pathway characteristics and elucidation of the structural basis of the tunnel gating. CAVER 3.0 paves the way for the study of important biochemical phenomena in the area of molecular transport, molecular recognition and enzymatic catalysis. The software is freely available as a multiplatform command-line application at http://www.caver.cz.

Utilization of wireless structural health monitoring as decision making tools for a condition and reliability-based assessment of railroad bridges

NASA Astrophysics Data System (ADS)

Flanigan, Katherine A.; Johnson, Nephi R.; Hou, Rui; Ettouney, Mohammed; Lynch, Jerome P.

2017-04-01

The ability to quantitatively assess the condition of railroad bridges facilitates objective evaluation of their robustness in the face of hazard events. Of particular importance is the need to assess the condition of railroad bridges in networks that are exposed to multiple hazards. Data collected from structural health monitoring (SHM) can be used to better maintain a structure by prompting preventative (rather than reactive) maintenance strategies and supplying quantitative information to aid in recovery. To that end, a wireless monitoring system is validated and installed on the Harahan Bridge which is a hundred-year-old long-span railroad truss bridge that crosses the Mississippi River near Memphis, TN. This bridge is exposed to multiple hazards including scour, vehicle/barge impact, seismic activity, and aging. The instrumented sensing system targets non-redundant structural components and areas of the truss and floor system that bridge managers are most concerned about based on previous inspections and structural analysis. This paper details the monitoring system and the analytical method for the assessment of bridge condition based on automated data-driven analyses. Two primary objectives of monitoring the system performance are discussed: 1) monitoring fatigue accumulation in critical tensile truss elements; and 2) monitoring the reliability index values associated with sub-system limit states of these members. Moreover, since the reliability index is a scalar indicator of the safety of components, quantifiable condition assessment can be used as an objective metric so that bridge owners can make informed damage mitigation strategies and optimize resource management on single bridge or network levels.

DETAIL VIEW OF THE STRUCTURE OF THE BASE OF THE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

DETAIL VIEW OF THE STRUCTURE OF THE BASE OF THE TEST STAND AND THE TAIL SECTION OF A REDSTONE (JUPITER) ROCKET. NOTE THE FLAME DEFLECTOR BEHIND THE STRUCTURE IN THE FOREGROUND. - Marshall Space Flight Center, Redstone Rocket (Missile) Test Stand, Dodd Road, Huntsville, Madison County, AL

Photograph of elevation and details of structure 841, used for ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Photograph of elevation and details of structure 841, used for repair project, dated 1973. Drawing in collection of Caretaker Site Office, Philadelphia Naval Business Center. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Structure No. 841, Delaware Avenue between East Fourth Street & Webster Avenue, League Island, Philadelphia, Philadelphia County, PA

Battery Berry Observation Station, detail, frame structure meeting older masonry ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Battery Berry Observation Station, detail, frame structure meeting older masonry building on west side of structure; view east - Fort McKinley, Battery Berry Observation Station, North side of Wood Side Drive approximately 80 feet east of Spring Cove Lane, Great Diamond Island, Portland, Cumberland County, ME

Designing and managing successful endangered species recovery programs

NASA Astrophysics Data System (ADS)

Clark, Tim W.; Crete, Ron; Cada, John

1989-03-01

Endangered species recovery is characterized by complexity and uncertainty in both its biological and organizational aspects. To improve performance in the organizational dimension, some models of organizations are briefly introduced with an emphasis on the organization as a system for processing information, i.e., for successfully dealing with the high uncertainty in the task environment. A strong task orientation,which rewards achievement of the primary goal, is suggested as ideal for this task, as is generative rationality, which encourages workers to observe, critique, and generate new ideas. The parallel organization—a flexible, participatory, problem-solving structure set up alongside traditional bureaucracies—is offered as a useful structure for meeting the demands of uncertainties encountered during recovery. Task forces and projects teams can be set up as parallel organizations. Improved managerial functions include coordinating roles to facilitate the flow and use of information; decision making to avoid “groupthink”—the defects, symptoms, and countermeasures are described; and productive, active management of the inevitable conflict. The inability of organizations to solve dilemmas, to examine their own structures and management, and to change themselves for more effective, efficient, and equitable performance is seen as the major obstacle to improved recovery programs. Some recommendations for effecting change in bureaucracies are made along with a call for case studies detailing the organizational dimensions of endangered species recovery programs.

Crystal-defect-induced facet-dependent electrocatalytic activity of 3D gold nanoflowers for the selective nanomolar detection of ascorbic acid.

PubMed

De, Sandip Kumar; Mondal, Subrata; Sen, Pintu; Pal, Uttam; Pathak, Biswarup; Rawat, Kuber Singh; Bardhan, Munmun; Bhattacharya, Maireyee; Satpati, Biswarup; De, Amitabha; Senapati, Dulal

2018-06-14

Understanding and exploring the decisive factors responsible for superlative catalytic efficiency is necessary to formulate active electrode materials for improved electrocatalysis and high-throughput sensing. This research demonstrates the ability of bud-shaped gold nanoflowers (AuNFs), intermediates in the bud-to-blossom gold nanoflower synthesis, to offer remarkable electrocatalytic efficiency in the oxidation of ascorbic acid (AA) at nanomolar concentrations. Multicomponent sensing in a single potential sweep is measured using differential pulse voltammetry while the kinetic parameters are estimated using electrochemical impedance spectroscopy. The outstanding catalytic activity of bud-structured AuNF [iAuNFp(Bud)/iGCp ≅ 100] compared with other bud-to-blossom intermediate nanostructures is explained by studying their structural transitions, charge distributions, crystalline patterns, and intrinsic irregularities/defects. Detailed microscopic analysis shows that density of crystal defects, such as edges, terraces, steps, ledges, kinks, and dislocation, plays a major role in producing the high catalytic efficiency. An associated ab initio simulation provides necessary support for the projected role of different crystal facets as selective catalytic sites. Density functional theory corroborates the appearance of inter- and intra-molecular hydrogen bonding within AA molecules to control the resultant fingerprint peak potentials at variable concentrations. Bud-structured AuNF facilitates AA detection at nanomolar levels in a multicomponent pathological sample.