Science.gov

Sample records for machinery conformational control

  1. Local Geometrical Machinery for Complexity and Control

    NASA Astrophysics Data System (ADS)

    Ivancevic, Vladimir G.; Reid, Darryn J.

    2015-11-01

    In this Chapter, we present local geometrical machinery for studying complexity and control, consisting of dynamics on Kähler manifolds, which combine three geometrical structures-Riemannian, symplectic and complex (Hermitian)-in a mutually compatible way. In other words, every Kähler manifold is simultaneously Riemannian, symplectic and complex (Hermitian). It is well known that Riemannian manifolds represent the stage on which Lagrangian dynamics is set, symplectic manifolds represent the stage for Hamiltonian dynamics, and complex (Hermitian) varieties comprise the stage for quantum dynamics. Therefore, Kähler manifolds represent the richest dynamical stage available where Lagrangian, Hamiltonian, and quantum dynamics all dance together.

  2. Electrical control of protein conformation.

    PubMed

    Wan, Alwin M D; Schur, Rebecca M; Ober, Christopher K; Fischbach, Claudia; Gourdon, Delphine; Malliaras, George G

    2012-05-08

    Conducting polymer devices that enable precise control of fibronectin conformation over macroscopic areas are reported. Single conformations as well as conformation gradients are achieved by applying an appropriate potential. These surfaces remain biologically relevant and support cell culture; hence, they may serve as a model to understand and control cell-surface interactions, with applications in basic research, medical diagnostics, and tissue engineering.

  3. Building, roof, with machinery penthouses on left and harbor control ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Building, roof, with machinery penthouses on left and harbor control tower on right. Camera facing south - Naval Supply Center, Broadway Complex, Warehouse, 911 West Broadway, San Diego, San Diego County, CA

  4. Integrated measure and control system for textile machinery

    NASA Astrophysics Data System (ADS)

    Liu, Yuantao; Zhao, Jinzhi; Zhao, Zexiang

    2010-12-01

    In this paper, textile mechanical drive control is researched. Textile machinery integrated measure and control system is established. The system is composed of micro-computer, PLC, transducer, implement device, all kinds of detective components and industrial Ethernet etc. Technology of industrial field bus control and Internet technique are applied. The system is on a background of textile production technique, such as spring, woven, chemical fiber, non-woven, dyeing and finishing. A network based open integrated control system is developed. Various characteristics of production technique flow and textile machinery movement discipline are presented. Configuration software is introduced according to user's control tasks. Final remote automatic controls are finished. This may make development cost reduced, and development periods shortened. Some problems in textile machinery development process are solved, which may make transparency factory and remote development realized.

  5. Elements of active vibration control for rotating machinery

    NASA Technical Reports Server (NTRS)

    Ulbrich, Heinz

    1990-01-01

    The success or failure of active vibration control is determined by the availability of suitable actuators, modeling of the entire system including all active elements, positioning of the actuators and sensors, and implementation of problem-adapted control concepts. All of these topics are outlined and their special problems are discussed in detail. Special attention is given to efficient modeling of systems, especially for considering the active elements. Finally, design methods for and the application of active vibration control on rotating machinery are demonstrated by several real applications.

  6. Systems and methods for autonomously controlling agricultural machinery

    DOEpatents

    Hoskinson, Reed L.; Bingham, Dennis N.; Svoboda, John M.; Hess, J. Richard

    2003-07-08

    Systems and methods for autonomously controlling agricultural machinery such as a grain combine. The operation components of a combine that function to harvest the grain have characteristics that are measured by sensors. For example, the combine speed, the fan speed, and the like can be measured. An important sensor is the grain loss sensor, which may be used to quantify the amount of grain expelled out of the combine. The grain loss sensor utilizes the fluorescence properties of the grain kernels and the plant residue to identify when the expelled plant material contains grain kernels. The sensor data, in combination with historical and current data stored in a database, is used to identify optimum operating conditions that will result in increased crop yield. After the optimum operating conditions are identified, an on-board computer can generate control signals that will adjust the operation of the components identified in the optimum operating conditions. The changes result in less grain loss and improved grain yield. Also, because new data is continually generated by the sensor, the system has the ability to continually learn such that the efficiency of the agricultural machinery is continually improved.

  7. Controlling complex networks with conformity behavior

    NASA Astrophysics Data System (ADS)

    Wang, Xu-Wen; Nie, Sen; Wang, Wen-Xu; Wang, Bing-Hong

    2015-09-01

    Controlling complex networks accompanied by common conformity behavior is a fundamental problem in social and physical science. Conformity behavior that individuals tend to follow the majority in their neighborhood is common in human society and animal communities. Despite recent progress in understanding controllability of complex networks, the existent controllability theories cannot be directly applied to networks associated with conformity. Here we propose a simple model to incorporate conformity-based decision making into the evolution of a network system, which allows us to employ the exact controllability theory to explore the controllability of such systems. We offer rigorous theoretical results of controllability for representative regular networks. We also explore real networks in different fields and some typical model networks, finding some interesting results that are different from the predictions of structural and exact controllability theory in the absence of conformity. We finally present an example of steering a real social network to some target states to further validate our controllability theory and tools. Our work offers a more realistic understanding of network controllability with conformity behavior and can have potential applications in networked evolutionary games, opinion dynamics and many other complex networked systems.

  8. 46 CFR 61.20-3 - Main and auxiliary machinery and associated equipment, including fluid control systems.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... control for the means of stopping machinery driving forced and induced draft fans, fuel oil transfer pumps, fuel oil unit pumps, and fans in the ventilation systems serving machinery and cargo spaces shall...

  9. Conservation of the RNA Transport Machineries and Their Coupling to Translation Control across Eukaryotes

    PubMed Central

    Vazquez-Pianzola, Paula; Suter, Beat

    2012-01-01

    Restriction of proteins to discrete subcellular regions is a common mechanism to establish cellular asymmetries and depends on a coordinated program of mRNA localization and translation control. Many processes from the budding of a yeast to the establishment of metazoan embryonic axes and the migration of human neurons, depend on this type of cell polarization. How factors controlling transport and translation assemble to regulate at the same time the movement and translation of transported mRNAs, and whether these mechanisms are conserved across kingdoms is not yet entirely understood. In this review we will focus on some of the best characterized examples of mRNA transport machineries, the “yeast locasome” as an example of RNA transport and translation control in unicellular eukaryotes, and on the Drosophila Bic-D/Egl/Dyn RNA localization machinery as an example of RNA transport in higher eukaryotes. This focus is motivated by the relatively advanced knowledge about the proteins that connect the localizing mRNAs to the transport motors and the many well studied proteins involved in translational control of specific transcripts that are moved by these machineries. We will also discuss whether the core of these RNA transport machineries and factors regulating mRNA localization and translation are conserved across eukaryotes. PMID:22666086

  10. Effective Dust Control Systems on Concrete Dowel Drilling Machinery

    PubMed Central

    Echt, Alan S.; Sanderson, Wayne T.; Mead, Kenneth R.; Feng, H. Amy; Farwick, Daniel R.; Farwick, Dawn Ramsey

    2016-01-01

    Rotary-type percussion dowel drilling machines, which drill horizontal holes in concrete pavement, have been documented to produce respirable crystalline silica concentrations above recommended exposure criteria. This places operators at potential risk for developing health effects from exposure. United States manufacturers of these machines offer optional dust control systems. The effectiveness of the dust control systems to reduce respirable dust concentrations on two types of drilling machines was evaluated under controlled conditions with the machines operating inside large tent structures in an effort to eliminate secondary exposure sources not related to the dowel-drilling operation. Area air samples were collected at breathing zone height at three locations around each machine. Through equal numbers of sampling rounds with the control systems randomly selected to be on or off, the control systems were found to significantly reduce respirable dust concentrations from a geometric mean of 54 mg per cubic meter to 3.0 mg per cubic meter on one machine and 57 mg per cubic meter to 5.3 mg per cubic meter on the other machine. This research shows that the dust control systems can dramatically reduce respirable dust concentrations by over 90% under controlled conditions. However, these systems need to be evaluated under actual work conditions to determine their effectiveness in reducing worker exposures to crystalline silica below hazardous levels. PMID:27074062

  11. Piezoelectric pushers for active vibration control of rotating machinery

    NASA Technical Reports Server (NTRS)

    Palazzolo, A. B.; Kascak, A. F.; Lin, R. R.; Montague, J.; Alexander, R. M.

    1989-01-01

    The active control of rotordynamic vibrations and stability by magnetic bearings and electromagnetic shakers was discussed extensively in the literature. These devices, though effective, are usually large in volume and add significant weight to the stator. The use of piezoelectric pushers may provide similar degrees of effectiveness in light, compact packages. Analyses are contained which extend quadratic regulator, pole placement and derivative feedback control methods to the prescribed displacement character of piezoelectric pushers. The structural stiffness of the pusher is also included in the theory. Tests are currently being conducted at NASA Lewis Research Center with piezoelectric pusher-based active vibration control. Results performed on the NASA test rig as preliminary verification of the related theory are presented.

  12. 46 CFR 61.20-3 - Main and auxiliary machinery and associated equipment, including fluid control systems.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ..., fuel oil unit pumps, and fans in the ventilation systems serving machinery and cargo spaces shall be..., including fluid control systems. 61.20-3 Section 61.20-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND... Equipment § 61.20-3 Main and auxiliary machinery and associated equipment, including fluid control systems...

  13. A software-based controller for generation of synchronized pulses for use with rotating machinery

    NASA Astrophysics Data System (ADS)

    Zurloye, Axel O.

    1989-08-01

    An IBM PC/AT based software package was developed to synchrotronize test equipment with rotating machinery. Up to eight outputs can be controlled independently. The pulse sequences can be as long as 254 shaft encoder revolutions and repeat until terminated. Unlike most purpose-built controllers, this software package is highly flexible. Complicated pulse sequences are easily generated and can quickly be modified using the built-in editor or a standard text editor. While the software requires a dedicated computer, implementation is easier and more cost effective than construction of a purpose-built controller.

  14. Test and theory for piezoelectric actuator-active vibration control of rotating machinery

    NASA Technical Reports Server (NTRS)

    Palazzolo, A. B.; Lin, R. R.; Alexander, R. M.; Kascak, A. F.; Montague, J.

    1989-01-01

    The application of piezoelectric actuators for active vibration control (AVC) of rotating machinery is examined. Theory is derived and the resulting predictions are shown to agree closely with results of tests performed on an air turbine driven-overhung rotor. The test results show significant reduction in unbalance, transient and sub-synchronous responses. Results from a 30-hour endurance test support the AVD system reliability. Various aspects of the electro-mechanical stability of the control system are also discussed and illustrated. Finally, application of the AVC system to an actual jet engine is discussed.

  15. Comparison of vibration amplitude supression vs. dynamic bearing load suppression in active vibration control of rotating machinery

    NASA Astrophysics Data System (ADS)

    Clark, William W.; Kim, J. H.; Marangoni, Roy D.

    1993-04-01

    This paper presents two optimal control methods for attenuating steady-state vibrations in rotating machinery. One method minimizes shaft displacements while the other minimizes dynamic bearing reaction forces. The two methods are applied to a model of a typical rotating machinery system, and their results are compared. It is found that displacement minimization can increase bearing loads, while bearing load minimization, on the other hand, decreases bearing loads without significant change in shaft displacements.

  16. Controlled traffic conservation tillage using small to middle sized machinery in China

    NASA Astrophysics Data System (ADS)

    Wang, Xiaoyan; Li, Hongwen; Gao, Huanwen; Du, Bing; He, Jin; Li, Wenying

    2005-09-01

    Research and farmers' experiences have demonstrated that reduced tillage helps maintain surface residues and provide substantial benefits in terms of water use efficiency, soil condition and productivity. However, the impact of field traffic and its influence on the soil when tillage is reduced or eliminated have been ignored, for small to middle-sized machinery are mostly used in Chinese agriculture. There is a need to study on wheel traffic impacts and to test controlled traffic farming system for Chinese conditions. This paper reports the five-year controlled traffic conservation tillage experiment in North China. Two trial plots (Spring Maize and Winter wheat) with four treatments and five replications were set up. The results indicated that controlled traffic conservation tillage could minimize the compaction of wheel traffic, make field operation timely and precisely, improve soil structure and increase soil moisture on crop zone which is beneficial to crop establishment and growth. With the accumulation of damages year after year, the impacts of random wheeling are becoming more notable. Heavier machinery appeared to compact soil to a greater depth, but even small tractors could compact the surface 10cm, critical to rainfall infiltration, to a remarkable degree. For the small-scaled controlled traffic system tested in this study, traffic lanes occupy about 20% of the land, but the yields were similar to those in the non-controlled traffic fields. Further test is needed for the long-term impacts of the traffic lanes on soil structure and crop yield and detailed analysis is necessary to develop a suitable controlled traffic farming system.

  17. Conformation-controlled binding kinetics of antibodies

    NASA Astrophysics Data System (ADS)

    Galanti, Marta; Fanelli, Duccio; Piazza, Francesco

    2016-01-01

    Antibodies are large, extremely flexible molecules, whose internal dynamics is certainly key to their astounding ability to bind antigens of all sizes, from small hormones to giant viruses. In this paper, we build a shape-based coarse-grained model of IgG molecules and show that it can be used to generate 3D conformations in agreement with single-molecule Cryo-Electron Tomography data. Furthermore, we elaborate a theoretical model that can be solved exactly to compute the binding rate constant of a small antigen to an IgG in a prescribed 3D conformation. Our model shows that the antigen binding process is tightly related to the internal dynamics of the IgG. Our findings pave the way for further investigation of the subtle connection between the dynamics and the function of large, flexible multi-valent molecular machines.

  18. Conformation-controlled binding kinetics of antibodies

    PubMed Central

    Galanti, Marta; Fanelli, Duccio; Piazza, Francesco

    2016-01-01

    Antibodies are large, extremely flexible molecules, whose internal dynamics is certainly key to their astounding ability to bind antigens of all sizes, from small hormones to giant viruses. In this paper, we build a shape-based coarse-grained model of IgG molecules and show that it can be used to generate 3D conformations in agreement with single-molecule Cryo-Electron Tomography data. Furthermore, we elaborate a theoretical model that can be solved exactly to compute the binding rate constant of a small antigen to an IgG in a prescribed 3D conformation. Our model shows that the antigen binding process is tightly related to the internal dynamics of the IgG. Our findings pave the way for further investigation of the subtle connection between the dynamics and the function of large, flexible multi-valent molecular machines. PMID:26755272

  19. 46 CFR 61.20-3 - Main and auxiliary machinery and associated equipment, including fluid control systems.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., including fluid control systems. 61.20-3 Section 61.20-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND... Equipment § 61.20-3 Main and auxiliary machinery and associated equipment, including fluid control systems... equipment, including the fluid control systems, as he feels necessary to check safe operation. (b) Remote...

  20. 46 CFR 61.20-3 - Main and auxiliary machinery and associated equipment, including fluid control systems.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., including fluid control systems. 61.20-3 Section 61.20-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND... Equipment § 61.20-3 Main and auxiliary machinery and associated equipment, including fluid control systems... equipment, including the fluid control systems, as he feels necessary to check safe operation. (b) Remote...

  1. 46 CFR 61.20-3 - Main and auxiliary machinery and associated equipment, including fluid control systems.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... equipment, including the fluid control systems, as he feels necessary to check safe operation. (b) Remote..., including fluid control systems. 61.20-3 Section 61.20-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND... Equipment § 61.20-3 Main and auxiliary machinery and associated equipment, including fluid control systems...

  2. Self-assembled amyloid fibrils with controllable conformational heterogeneity

    NASA Astrophysics Data System (ADS)

    Lee, Gyudo; Lee, Wonseok; Lee, Hyungbeen; Lee, Chang Young; Eom, Kilho; Kwon, Taeyun

    2015-11-01

    Amyloid fibrils are a hallmark of neurodegenerative diseases and exhibit a conformational diversity that governs their pathological functions. Despite recent findings concerning the pathological role of their conformational diversity, the way in which the heterogeneous conformations of amyloid fibrils can be formed has remained elusive. Here, we show that microwave-assisted chemistry affects the self-assembly process of amyloid fibril formation, which results in their conformational heterogeneity. In particular, microwave-assisted chemistry allows for delicate control of the thermodynamics of the self-assembly process, which enabled us to tune the molecular structure of β-lactoglobulin amyloid fibrils. The heterogeneous conformations of amyloid fibrils, which can be tuned with microwave-assisted chemistry, are attributed to the microwave-driven thermal energy affecting the electrostatic interaction during the self-assembly process. Our study demonstrates how microwave-assisted chemistry can be used to gain insight into the origin of conformational heterogeneity of amyloid fibrils as well as the design principles showing how the molecular structures of amyloid fibrils can be controlled.

  3. Christian Religiosity, Self-Control and Social Conformity

    ERIC Educational Resources Information Center

    Welch, Michael R.; Tittle, Charles R.; Grasmick, Harold G.

    2006-01-01

    Survey data from a southwestern metropolitan area are used to analyze whether the ability of personal Christian religiosity to predict social conformity is spuriously due to self-control. Results indicate that both personal religiosity and self-control display statistically significant, independent negative net relationships with many forms of…

  4. Christian Religiosity, Self-Control and Social Conformity

    ERIC Educational Resources Information Center

    Welch, Michael R.; Tittle, Charles R.; Grasmick, Harold G.

    2006-01-01

    Survey data from a southwestern metropolitan area are used to analyze whether the ability of personal Christian religiosity to predict social conformity is spuriously due to self-control. Results indicate that both personal religiosity and self-control display statistically significant, independent negative net relationships with many forms of…

  5. Conformable M3 Microsystems for Aerodynamic Control

    DTIC Science & Technology

    2007-11-02

    we have fabricated sensors, actuators, and electronics all on the same chip. Control: • A CMOS control circuit has been designed and sent to MOSIS ...macro aerodynamic devices. (3) After the chip from MOSIS is fabricated, it will be tested to confirm that it works as designed. (4) The process and...identify the separation point from the outputs of shear stress sensors and drive the corresponding actuators. The layout has been sent to MOSIS for

  6. Integrity of SRP RNA is ensured by La and the nuclear RNA quality control machinery.

    PubMed

    Leung, Eileen; Schneider, Claudia; Yan, Fu; Mohi-El-Din, Hatem; Kudla, Grzegorz; Tuck, Alex; Wlotzka, Wiebke; Doronina, Victoria A; Bartley, Ralph; Watkins, Nicholas J; Tollervey, David; Brown, Jeremy D

    2014-01-01

    The RNA component of signal recognition particle (SRP) is transcribed by RNA polymerase III, and most steps in SRP biogenesis occur in the nucleolus. Here, we examine processing and quality control of the yeast SRP RNA (scR1). In common with other pol III transcripts, scR1 terminates in a U-tract, and mature scR1 retains a U4-5 sequence at its 3' end. In cells lacking the exonuclease Rex1, scR1 terminates in a longer U5-6 tail that presumably represents the primary transcript. The 3' U-tract of scR1 is protected from aberrant processing by the La homologue, Lhp1 and overexpressed Lhp1 apparently competes with both the RNA surveillance system and SRP assembly factors. Unexpectedly, the TRAMP and exosome nuclear RNA surveillance complexes are also implicated in protecting the 3' end of scR1, which accumulates in the nucleolus of cells lacking the activities of these complexes. Misassembled scR1 has a primary degradation pathway in which Rrp6 acts early, followed by TRAMP-stimulated exonuclease degradation by the exosome. We conclude that the RNA surveillance machinery has key roles in both SRP biogenesis and quality control of the RNA, potentially facilitating the decision between these alternative fates.

  7. Conformal grasping using feedback controlled bubble actuator array

    NASA Astrophysics Data System (ADS)

    Carrigan, Wei; Stein, Richard; Mittal, Manoj; Wijesundara, Muthu B. J.

    2014-06-01

    This paper presents an implementation of a bubble actuator array (BAA) based active robotic skin, a modular system, onto existing low cost robotic end-effectors or prosthetic hands for conformal grasping of objects. The active skin is comprised of pneumatically controlled polyurethane rubber bubbles with overlaid sensors for feedback control. Sensor feedback allows the BAA based robotic skin to conformally grasp an object with an explicit uniform force distribution. The bubble actuator array reported here is capable of applying up to 4N of force at each point of contact and tested for conformally grasping objects with a radius of curvature up to 57.15mm. Once integrated onto a two-finger gripper with one degree of freedom (DOF), the active skin was shown to reduce point of contact forces of up to 50% for grasped objects.

  8. Cell cytoskeletal conformation under reversible thermal control

    NASA Astrophysics Data System (ADS)

    Chang, Ting-Ya; Yang, Chung-Yao; Liao, Kai-Wei; Andrew Yeh, J.; Cheng, Chao-Min

    2013-12-01

    In order to assess the role of cytoskeletal structure in modulating cell surface topography during cell transformation, we investigated cytoskeletal organization of Madin-Darby canine kidney (MDCK) epithelial cells at different thermal gradients. Specifically, we examined actin polymerization as a function of temperature in a controlled thermal environment. After applying an increase in temperature of 5 °C, we observed fewer actin filaments in the network, as these molecular polymers depolymerized. Partial stress fibers of MDCK cells could be rearranged, but some of them were disrupted irreversibly after a second thermal treatment, and MDCK cells underwent apoptosis at higher temperatures as well.

  9. Improve machinery vibration data

    SciTech Connect

    Haq, I. )

    1993-03-01

    Continuous monitoring and periodic logging of machinery information are the best ways to measure current performance and predict availability. Decisions made on time-based information analysis are only as good as the quality of the data. Methods for data acquisition must conform to standards that ensure data are free of errors and ambiguity. This paper discusses the data acquisition framework; data collection techniques; conventions and documentation; transduces operation; transduces selection and application; transducer noise; and vital features of a diagnostic instrument.

  10. Organization, integration, and assembly of genetic and epigenetic regulatory machinery in nuclear microenvironments: implications for biological control in cancer.

    PubMed

    Stein, Gary S; Zaidi, Sayyed K; Stein, Janet L; Lian, Jane B; van Wijnen, Andre J; Montecino, Martin; Young, Daniel W; Javed, Amjad; Pratap, Jitesh; Choi, Je-Yong; Ali, Syed A; Pande, Sandhya; Hassan, Mohammad Q

    2009-02-01

    There is growing awareness that the fidelity of gene expression necessitates coordination of transcription factor metabolism and organization of genes and regulatory proteins within the three-dimensional context of nuclear architecture. The regulatory machinery that governs genetic and epigenetic control of gene expression is compartmentalized in nuclear microenvironments. Temporal and spatial parameters of regulatory complex organization and assembly are functionally linked to biological control and are compromised with the onset and progression of tumorigenesis. High throughput imaging of cells, tissues, and tumors, including live cell analysis, is expanding research's capabilities toward translating components of nuclear organization into novel strategies for cancer diagnosis and therapy.

  11. Conformational stability as a design target to control protein aggregation.

    PubMed

    Costanzo, Joseph A; O'Brien, Christopher J; Tiller, Kathryn; Tamargo, Erin; Robinson, Anne Skaja; Roberts, Christopher J; Fernandez, Erik J

    2014-05-01

    Non-native protein aggregation is a prevalent problem occurring in many biotechnological manufacturing processes and can compromise the biological activity of the target molecule or induce an undesired immune response. Additionally, some non-native aggregation mechanisms lead to amyloid fibril formation, which can be associated with debilitating diseases. For natively folded proteins, partial or complete unfolding is often required to populate aggregation-prone conformational states, and therefore one proposed strategy to mitigate aggregation is to increase the free energy for unfolding (ΔGunf) prior to aggregation. A computational design approach was tested using human γD crystallin (γD-crys) as a model multi-domain protein. Two mutational strategies were tested for their ability to reduce/increase aggregation rates by increasing/decreasing ΔGunf: stabilizing the less stable domain and stabilizing the domain-domain interface. The computational protein design algorithm, RosettaDesign, was implemented to identify point variants. The results showed that although the predicted free energies were only weakly correlated with the experimental ΔGunf values, increased/decreased aggregation rates for γD-crys correlated reasonably well with decreases/increases in experimental ΔGunf, illustrating improved conformational stability as a possible design target to mitigate aggregation. However, the results also illustrate that conformational stability is not the sole design factor controlling aggregation rates of natively folded proteins.

  12. A conformational switch controls hepatitis delta virus ribozyme catalysis.

    PubMed

    Ke, Ailong; Zhou, Kaihong; Ding, Fang; Cate, Jamie H D; Doudna, Jennifer A

    2004-05-13

    Ribozymes enhance chemical reaction rates using many of the same catalytic strategies as protein enzymes. In the hepatitis delta virus (HDV) ribozyme, site-specific self-cleavage of the viral RNA phosphodiester backbone requires both divalent cations and a cytidine nucleotide. General acid-base catalysis, substrate destabilization and global and local conformational changes have all been proposed to contribute to the ribozyme catalytic mechanism. Here we report ten crystal structures of the HDV ribozyme in its pre-cleaved state, showing that cytidine is positioned to activate the 2'-OH nucleophile in the precursor structure. This observation supports its proposed role as a general base in the reaction mechanism. Comparison of crystal structures of the ribozyme in the pre- and post-cleavage states reveals a significant conformational change in the RNA after cleavage and that a catalytically critical divalent metal ion from the active site is ejected. The HDV ribozyme has remarkable chemical similarity to protein ribonucleases and to zymogens for which conformational dynamics are integral to biological activity. This finding implies that RNA structural rearrangements control the reactivity of ribozymes and ribonucleoprotein enzymes.

  13. Using Chemicals to Optimize Conformance Control in Fractured Reservoirs

    SciTech Connect

    Seright, Randall S.; Liang, Jenn-Tai; Schrader, Richard; Hagstrom II, John; Wang, Ying; Kumar, Ananad; Wavrik, Kathryn

    2001-10-29

    This report describes work performed during the third and final year of the project, Using Chemicals to Optimize Conformance Control in Fractured Reservoirs. This research project had three objectives. The first objective was to develop a capability to predict and optimize the ability of gels to reduce permeability to water more than that to oil or gas. The second objective was to develop procedures for optimizing blocking agent placement in wells where hydraulic fractures cause channeling problems. The third objective was to develop procedures to optimize blocking agent placement in naturally fractured reservoirs.

  14. Outer membrane machinery and alginate synthesis regulators control membrane vesicle production in Pseudomonas aeruginosa.

    PubMed

    Tashiro, Yosuke; Sakai, Ryosuke; Toyofuku, Masanori; Sawada, Isao; Nakajima-Kambe, Toshiaki; Uchiyama, Hiroo; Nomura, Nobuhiko

    2009-12-01

    The opportunistic human bacterial pathogen Pseudomonas aeruginosa produces membrane vesicles (MVs) in its surrounding environment. Several features of the P. aeruginosa MV production mechanism are still unknown. We previously observed that depletion of Opr86, which has a role in outer membrane protein (OMP) assembly, resulted in hypervesiculation. In this study, we showed that the outer membrane machinery and alginate synthesis regulatory machinery are closely related to MV production in P. aeruginosa. Depletion of Opr86 resulted in increased expression of the periplasmic serine protease MucD, suggesting that the accumulation of misfolded OMPs in the periplasm is related to MV production. Indeed, the mucD mutant showed a mucoid phenotype and the mucD mutation caused increased MV production. Strains with the gene encoding alginate synthetic regulator AlgU, MucA, or MucB deleted also caused altered MV production. Overexpression of either MucD or AlgW serine proteases resulted in decreased MV production, suggesting that proteases localized in the periplasm repress MV production in P. aeruginosa. Deletion of mucD resulted in increased MV proteins, even in strains with mutations in the Pseudomonas quinolone signal (PQS), which serves as a positive regulator of MV production. This study suggests that misfolded OMPs may be important for MV production, in addition to PQS, and that these regulators act in independent pathways.

  15. Binding Affinities Controlled by Shifting Conformational Equilibria: Opportunities and Limitations

    PubMed Central

    Michielssens, Servaas; de Groot, Bert L.; Grubmüller, Helmut

    2015-01-01

    Conformational selection is an established mechanism in molecular recognition. Despite its power to explain binding events, it is hardly used in protein/ligand design to modulate molecular recognition. Here, we explore the opportunities and limitations of design by conformational selection. Using appropriate thermodynamic cycles, our approach predicts the effects of a conformational shift on binding affinity and also allows one to disentangle the effects induced by a conformational shift from other effects influencing the binding affinity. The method is assessed and applied to explain the contribution of a conformational shift on the binding affinity of six ubiquitin mutants showing different conformational shifts in six different complexes. PMID:25992736

  16. 49. Machinery rooms on north tower. Facing north. Machinery rooms ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    49. Machinery rooms on north tower. Facing north. Machinery rooms contain all motors, motor controllers, and gears for operating one span, in this case, the north span. Note bell with continuous operating clapper for use as fog signals. - Henry Ford Bridge, Spanning Cerritos Channel, Los Angeles-Long Beach Harbor, Los Angeles, Los Angeles County, CA

  17. The RNAi machinery controls distinct responses to environmental signals in the basal fungus Mucor circinelloides

    DOE PAGES

    Nicolas, Francisco E.; Vila, Ana; Moxon, Simon; ...

    2015-03-25

    Here, RNA interference (RNAi) is a conserved mechanism of genome defence that can also have a role in the regulation of endogenous functions through endogenous small RNAs (esRNAs). In fungi, knowledge of the functions regulated by esRNAs has been hampered by lack of clear phenotypes in most mutants affected in the RNAi machinery. Mutants of Mucor circinelloides affected in RNAi genes show defects in physiological and developmental processes, thus making Mucor an outstanding fungal model for studying endogenous functions regulated by RNAi. Some classes of Mucor esRNAs map to exons (ex-siRNAs) and regulate expression of the genes from which theymore » derive. To have a broad picture of genes regulated by the silencing machinery during vegetative growth, we have sequenced and compared the mRNA profiles of mutants in the main RNAi genes by using RNA-seq. In addition, we have achieved a more complete phenotypic characterization of silencing mutants Deletion of any main RNAi gene provoked a deep impact in mRNA accumulation at exponential and stationary growth. Genes showing increased mRNA levels, as expected for direct ex-siRNAs targets, but also genes with decreased expression were detected, suggesting that, most probably, the initial ex-siRNA targets regulate the expression of other genes, which can be up- or down-regulated. Expression of 50% of the genes was dependent on more than one RNAi gene in agreement with the existence of several classes of ex-siRNAs produced by different combinations of RNAi proteins. These combinations of proteins have also been involved in the regulation of different cellular processes. Besides genes regulated by the canonical RNAi pathway, this analysis identified processes, such as growth at low pH and sexual interaction that are regulated by a dicer-independent non-canonical RNAi pathway. In conclusion, this work shows that the RNAi pathways play a relevant role in the regulation of a significant number of endogenous genes in M

  18. Using Chemicals to Optimize Conformance Control in Fractured Reservoirs

    SciTech Connect

    Seright, Randall S.; Liang, Jenn-Tai; Schrader, Richard; Hagstrom II, John; Liu, Jin; Wavrik, Kathryn

    1999-09-27

    This report describes work performed during the first year of the project, ''Using Chemicals to Optimize Conformance Control in Fractured Reservoirs.'' This research project has three objectives. The first objective is to develop a capability to predict and optimize the ability of gels to reduce permeability to water more than that to oil or gas. The second objective is to develop procedures for optimizing blocking agent placement in wells where hydraulic fractures cause channeling problems. The third objective is to develop procedures to optimize blocking agent placement in naturally fractured reservoirs. This research project consists of three tasks, each of which addresses one of the above objectives. Our work is directed at both injection wells and production wells and at vertical, horizontal, and highly deviated wells.

  19. Insulin signaling controls neurotransmission via the 4eBP-dependent modification of the exocytotic machinery

    PubMed Central

    Mahoney, Rebekah Elizabeth; Azpurua, Jorge; Eaton, Benjamin A

    2016-01-01

    Altered insulin signaling has been linked to widespread nervous system dysfunction including cognitive dysfunction, neuropathy and susceptibility to neurodegenerative disease. However, knowledge of the cellular mechanisms underlying the effects of insulin on neuronal function is incomplete. Here, we show that cell autonomous insulin signaling within the Drosophila CM9 motor neuron regulates the release of neurotransmitter via alteration of the synaptic vesicle fusion machinery. This effect of insulin utilizes the FOXO-dependent regulation of the thor gene, which encodes the Drosophila homologue of the eif-4e binding protein (4eBP). A critical target of this regulatory mechanism is Complexin, a synaptic protein known to regulate synaptic vesicle exocytosis. We find that the amounts of Complexin protein observed at the synapse is regulated by insulin and genetic manipulations of Complexin levels support the model that increased synaptic Complexin reduces neurotransmission in response to insulin signaling. DOI: http://dx.doi.org/10.7554/eLife.16807.001 PMID:27525480

  20. Instability in Rotating Machinery

    NASA Technical Reports Server (NTRS)

    1985-01-01

    The proceedings contain 45 papers on a wide range of subjects including flow generated instabilities in fluid flow machines, cracked shaft detection, case histories of instability phenomena in compressors, turbines, and pumps, vibration control in turbomachinery (including antiswirl techniques), and the simulation and estimation of destabilizing forces in rotating machines. The symposium was held to serve as an update on the understanding and control of rotating machinery instability problems.

  1. 46 CFR 130.450 - Machinery alarms.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Machinery alarms. 130.450 Section 130.450 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OFFSHORE SUPPLY VESSELS VESSEL CONTROL, AND MISCELLANEOUS EQUIPMENT AND SYSTEMS Automation of Unattended Machinery Spaces § 130.450 Machinery alarms....

  2. 46 CFR 130.450 - Machinery alarms.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Machinery alarms. 130.450 Section 130.450 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OFFSHORE SUPPLY VESSELS VESSEL CONTROL, AND MISCELLANEOUS EQUIPMENT AND SYSTEMS Automation of Unattended Machinery Spaces § 130.450 Machinery alarms. (a...

  3. 46 CFR 130.450 - Machinery alarms.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 4 2014-10-01 2014-10-01 false Machinery alarms. 130.450 Section 130.450 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OFFSHORE SUPPLY VESSELS VESSEL CONTROL, AND MISCELLANEOUS EQUIPMENT AND SYSTEMS Automation of Unattended Machinery Spaces § 130.450 Machinery alarms. (a...

  4. 46 CFR 130.450 - Machinery alarms.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Machinery alarms. 130.450 Section 130.450 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OFFSHORE SUPPLY VESSELS VESSEL CONTROL, AND MISCELLANEOUS EQUIPMENT AND SYSTEMS Automation of Unattended Machinery Spaces § 130.450 Machinery alarms. (a...

  5. 46 CFR 130.450 - Machinery alarms.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Machinery alarms. 130.450 Section 130.450 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OFFSHORE SUPPLY VESSELS VESSEL CONTROL, AND MISCELLANEOUS EQUIPMENT AND SYSTEMS Automation of Unattended Machinery Spaces § 130.450 Machinery alarms. (a...

  6. Application of owner technical management in hydraulic machinery and electrical equipment investment target control

    NASA Astrophysics Data System (ADS)

    Luo, H.

    2012-11-01

    Using technical means in investment target control is an effective method to improve investment benefit of a construction project. Take the practice of construction and management in hydropower station as an example, the investment and management need of the owner is put forward through the investment target decision-making process of electromechanical equipment. Owner technical management in the specific application measures and effects of investment target control was discussed in the paper, and the revelation in investment target control application of owner technical management was also summarized. The paper is aimed to provide a useful reference for the investment target control work in the construction of electromechanical equipment.

  7. 9 CFR 318.24 - Product prepared using advanced meat/bone separation machinery; process control.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... than skulls or vertebral column bones of cattle 30 months of age and older as provided in § 310.22 of... control. (1) The production process is not in control if the skulls entering the AMR system contain any...) Brain or trigeminal ganglia. Skulls that enter the AMR system have tissues of brain or...

  8. 9 CFR 318.24 - Product prepared using advanced meat/bone separation machinery; process control.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... than skulls or vertebral column bones of cattle 30 months of age and older as provided in § 310.22 of... control. (1) The production process is not in control if the skulls entering the AMR system contain any...) Brain or trigeminal ganglia. Skulls that enter the AMR system have tissues of brain or...

  9. 9 CFR 318.24 - Product prepared using advanced meat/bone separation machinery; process control.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... than skulls or vertebral column bones of cattle 30 months of age and older as provided in § 310.22 of... control. (1) The production process is not in control if the skulls entering the AMR system contain any...) Brain or trigeminal ganglia. Skulls that enter the AMR system have tissues of brain or...

  10. 9 CFR 318.24 - Product prepared using advanced meat/bone separation machinery; process control.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... than skulls or vertebral column bones of cattle 30 months of age and older as provided in § 310.22 of... control. (1) The production process is not in control if the skulls entering the AMR system contain any...) Brain or trigeminal ganglia. Skulls that enter the AMR system have tissues of brain or...

  11. 9 CFR 318.24 - Product prepared using advanced meat/bone separation machinery; process control.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... than skulls or vertebral column bones of cattle 30 months of age and older as provided in § 310.22 of... control. (1) The production process is not in control if the skulls entering the AMR system contain any...) Brain or trigeminal ganglia. Skulls that enter the AMR system have tissues of brain or...

  12. An in vivo control map for the eukaryotic mRNA translation machinery.

    PubMed

    Firczuk, Helena; Kannambath, Shichina; Pahle, Jürgen; Claydon, Amy; Beynon, Robert; Duncan, John; Westerhoff, Hans; Mendes, Pedro; McCarthy, John Eg

    2013-01-01

    Rate control analysis defines the in vivo control map governing yeast protein synthesis and generates an extensively parameterized digital model of the translation pathway. Among other non-intuitive outcomes, translation demonstrates a high degree of functional modularity and comprises a non-stoichiometric combination of proteins manifesting functional convergence on a shared maximal translation rate. In exponentially growing cells, polypeptide elongation (eEF1A, eEF2, and eEF3) exerts the strongest control. The two other strong control points are recruitment of mRNA and tRNA(i) to the 40S ribosomal subunit (eIF4F and eIF2) and termination (eRF1; Dbp5). In contrast, factors that are found to promote mRNA scanning efficiency on a longer than-average 5'untranslated region (eIF1, eIF1A, Ded1, eIF2B, eIF3, and eIF5) exceed the levels required for maximal control. This is expected to allow the cell to minimize scanning transition times, particularly for longer 5'UTRs. The analysis reveals these and other collective adaptations of control shared across the factors, as well as features that reflect functional modularity and system robustness. Remarkably, gene duplication is implicated in the fine control of cellular protein synthesis.

  13. Relationships between Psychological Androgyny, Social Conformity, and Perceived Locus of Control.

    ERIC Educational Resources Information Center

    Brehony, Kathleen A.; Geller, E. Scott

    1981-01-01

    Compared the decisions and attitudes of sex-stereotyped and androgynous individuals in a social conformity paradigm and on two measures of locus of control. Stereotypic females conformed significantly more often than androgynous females and stereotypic males. Androgynous females were more internal in locus of control than stereotypic females.…

  14. Naval Open Architecture Machinery Control Systems for Next Generation Integrated Power Systems

    DTIC Science & Technology

    2012-05-01

    Smart Grid standards. This paper describes the state-of-the-art of control system technology applicable to Compact Power and NGIPS to help focus...product- line vision. This vision includes the application of Smart Grid and Microgrid standards related to Power Electronics controls to address the...commercial ships. NGIPS will move naval electric plant designs away from commercial building designs towards emerging Smart Grid Substation and Microgrid

  15. Experimental study on active structural acoustic control of rotating machinery using rotating piezo-based inertial actuators

    NASA Astrophysics Data System (ADS)

    Zhao, G.; Alujević, N.; Depraetere, B.; Pinte, G.; Swevers, J.; Sas, P.

    2015-07-01

    In this paper, two Piezo-Based Rotating Inertial Actuators (PBRIAs) are considered for the suppression of the structure-borne noise radiated from rotating machinery. As add-on devices, they can be directly mounted on a rotational shaft, in order to intervene as early as possible in the transfer path between disturbance and the noise radiating surfaces. A MIMO (Multi-Input-Multi-Output) form of the FxLMS control algorithm is employed to generate the appropriate actuation signals, relying on a linear interpolation scheme to approximate time varying secondary plants. The proposed active vibration control approach is tested on an experimental test bed comprising a rotating shaft mounted in a frame to which a noise-radiating plate is attached. The disturbance force is introduced by an electro-dynamic shaker. The experimental results show that when the shaft spins below 180 rpm, more than a 7 dB reduction can be achieved in terms of plate vibrations, along with a reduction in the same order of magnitude in terms of noise radiation.

  16. Use of piezoelectric actuators in active vibration control of rotating machinery

    NASA Technical Reports Server (NTRS)

    Lin, Reng Rong; Palazzolo, Alan B.; Kascak, Albert F.; Montague, Gerald

    1990-01-01

    Theoretical and test results for the development of piezoelectric-actuator-based active vibration control (AVC) are presented. The evolution of this technology starts with an ideal model of the actuator and progresses to a more sophisticated model where the pushers force the squirrel cage ball bearing supports of a rotating shaft. The piezoelectric pushers consist of a stack of piezoelectric ceramic disks that are arranged on top of one another and connected in parallel electrically. This model consists of a prescribed displacement that is proportional to the input voltage and a spring that represents the stiffness of the stack of piezoelectric disks. System tests were carried out to stabilize the AVC system, verify its effectiveness in controlling vibration, and confirm the theory presented.

  17. Active vibration control of rotating machinery with a hybrid piezohydraulic actuator system

    SciTech Connect

    Tang, P.; Palazzolo, A.B.; Kascak, A.F.; Montague, G.T.

    1995-10-01

    An integrated, compact piezohydraulic actuator system for active vibration control was designed and developed with a primary application for gas turbine aircraft engines. Copper tube was chosen as the transmission line material for ease of assembly. Liquid plastic, which meets incompressibility and low-viscosity requirements, was adjusted to provide optimal actuator performance. Variants of the liquid plastic have been prepared with desired properties between {minus}40 F and 400 F. The effectiveness of this hybrid actuator for active vibration control (AVC) was demonstrated for suppressing critical speed vibration through two critical speeds for various levels of intentionally placed imbalance. A high-accuracy closed-loop simulation, which combines both finite element and state space methods, was applied for the closed-loop unbalance response simulation with/without AVC. Good correlation between the simulation and test results was achieved.

  18. Use of piezoelectric actuators in active vibration control of rotating machinery

    NASA Technical Reports Server (NTRS)

    Lin, Reng Rong; Palazzolo, Alan B.; Kascak, Albert F.; Montague, Gerald

    1990-01-01

    Theoretical and test results for the development of piezoelectric-actuator-based active vibration control (AVC) are presented. The evolution of this technology starts with an ideal model of the actuator and progresses to a more sophisticated model where the pushers force the squirrel cage ball bearing supports of a rotating shaft. The piezoelectric pushers consist of a stack of piezoelectric ceramic disks that are arranged on top of one another and connected in parallel electrically. This model consists of a prescribed displacement that is proportional to the input voltage and a spring that represents the stiffness of the stack of piezoelectric disks. System tests were carried out to stabilize the AVC system, verify its effectiveness in controlling vibration, and confirm the theory presented.

  19. Privileged crosstalk between TRPV1 channels and mitochondrial calcium shuttling machinery controls nociception.

    PubMed

    Nita, Iulia I; Caspi, Yaki; Gudes, Sagi; Fishman, Dimitri; Lev, Shaya; Hersfinkel, Michal; Sekler, Israel; Binshtok, Alexander M

    2016-12-01

    The nociceptive noxious heat-activated receptor - TRPV1, conducts calcium and sodium, thus producing a depolarizing receptor potential, leading to activation of nociceptive neurons. TRPV1-mediated calcium and sodium influx is negatively modulated by calcium, via calcium-dependent desensitization of TRPV1 channels. A mitochondrial Ca(2+) uniporter - MCU, controls mitochondrial Ca(2+) entry while a sodium/calcium transporter - NCLX shapes calcium and sodium transients by mediating sodium entry into and removing calcium from the mitochondria. The functional interplay between TRPV1, MCU and NCLX, in controlling the cytosolic and mitochondrial calcium and sodium transients and subsequently the nociceptive excitability, is poorly understood. Here, we used cytosolic and mitochondrial fluorescent calcium and sodium imaging together with electrophysiological recordings of TRPV1-induced currents in HEK293T cells and nociceptor-like dissociated rat dorsal root ganglion neurons, while modulating NCLX or MCU expression using specific small interfering RNA (siNCLX). We show that the propagation of the TRPV1-induced cytosolic calcium and sodium fluxes into mitochondria is dependent on coordinated activity of NCLX and MCU. Thus, knocking-down of NCLX triggers down regulation of MCU dependent mitochondrial Ca(2+) uptake. This in turn decreases rate and amplitude of TRPV1-mediated cytosolic calcium, which inhibits capsaicin-induced inward current and neuronal firing. TRPV1-mediated currents were fully rescued by intracellular inclusion of the fast calcium chelator BAPTA. Finally, NCLX controls capsaicin-induced cell death, by supporting massive mitochondrial Ca(2+) shuttling. Altogether, our results suggest that NCLX, by regulating cytosolic and mitochondrial ionic transients, modulates calcium-dependent desensitization of TRPV1 channels, thereby, controlling nociceptive signaling.

  20. The RNA-Binding Protein SYNCRIP Is a Component of the Hepatocyte Exosomal Machinery Controlling MicroRNA Sorting.

    PubMed

    Santangelo, Laura; Giurato, Giorgio; Cicchini, Carla; Montaldo, Claudia; Mancone, Carmine; Tarallo, Roberta; Battistelli, Cecilia; Alonzi, Tonino; Weisz, Alessandro; Tripodi, Marco

    2016-10-11

    Despite clear evidence that exosomal microRNAs (miRNAs) are able to modulate the cellular microenvironment and that exosomal RNA cargo selection is deregulated in pathological conditions, the mechanisms controlling specific RNA sorting into extracellular vesicles are still poorly understood. Here, we identified the RNA binding protein SYNCRIP (synaptotagmin-binding cytoplasmic RNA-interacting protein; also known as hnRNP-Q or NSAP1) as a component of the hepatocyte exosomal miRNA sorting machinery. SYNCRIP knockdown impairs sorting of miRNAs in exosomes. Furthermore, SYNCRIP directly binds to specific miRNAs enriched in exosomes sharing a common extra-seed sequence (hEXO motif). The hEXO motif has a role in the regulation of miRNA localization, since embedment of this motif into a poorly exported miRNA enhances its loading into exosomes. This evidence provides insights into the mechanisms of miRNA exosomal sorting process. Moreover, these findings open the way for the possible selective modification of the miRNAs exosomal cargo. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  1. Nucleosome geometry and internucleosomal interactions control the chromatin fiber conformation.

    PubMed

    Kepper, Nick; Foethke, Dietrich; Stehr, Rene; Wedemann, Gero; Rippe, Karsten

    2008-10-01

    Based on model structures with atomic resolution, a coarse-grained model for the nucleosome geometry was implemented. The dependence of the chromatin fiber conformation on the spatial orientation of nucleosomes and the path and length of the linker DNA was systematically explored by Monte Carlo simulations. Two fiber types were analyzed in detail that represent nucleosome chains without and with linker histones, respectively: two-start helices with crossed-linker DNA (CL conformation) and interdigitated one-start helices (ID conformation) with different nucleosome tilt angles. The CL conformation was derived from a tetranucleosome crystal structure that was extended into a fiber. At thermal equilibrium, the fiber shape persisted but relaxed into a structure with a somewhat lower linear mass density of 3.1 +/- 0.1 nucleosomes/11 nm fiber. Stable ID fibers required local nucleosome tilt angles between 40 degrees and 60 degrees. For these configurations, much higher mass densities of up to 7.9 +/- 0.2 nucleosomes/11 nm fiber were obtained. A model is proposed, in which the transition between a CL and ID fiber is mediated by relatively small changes of the local nucleosome geometry. These were found to be in very good agreement with changes induced by linker histone H1 binding as predicted from the high resolution model structures.

  2. 46 CFR 176.804 - Machinery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... control mechanisms including primary and alternate means of starting machinery; (c) Inspection of all... remote operating positions; (g) Operational test of all overboard discharge and intake valves and...

  3. Cellular Cations Control Conformational Switching of Inositol Pyrophosphate Analogues.

    PubMed

    Hager, Anastasia; Wu, Mingxuan; Wang, Huanchen; Brown, Nathaniel W; Shears, Stephen B; Veiga, Nicolás; Fiedler, Dorothea

    2016-08-22

    The inositol pyrophosphate messengers (PP-InsPs) are emerging as an important class of cellular regulators. These molecules have been linked to numerous biological processes, including insulin secretion and cancer cell migration, but how they trigger such a wide range of cellular responses has remained unanswered in many cases. Here, we show that the PP-InsPs exhibit complex speciation behaviour and propose that a unique conformational switching mechanism could contribute to their multifunctional effects. We synthesised non-hydrolysable bisphosphonate analogues and crystallised the analogues in complex with mammalian PPIP5K2 kinase. Subsequently, the bisphosphonate analogues were used to investigate the protonation sequence, metal-coordination properties, and conformation in solution. Remarkably, the presence of potassium and magnesium ions enabled the analogues to adopt two different conformations near physiological pH. Understanding how the intrinsic chemical properties of the PP-InsPs can contribute to their complex signalling outputs will be essential to elucidate their regulatory functions.

  4. Control of serotonin transporter phosphorylation by conformational state.

    PubMed

    Zhang, Yuan-Wei; Turk, Benjamin E; Rudnick, Gary

    2016-05-17

    Serotonin transporter (SERT) is responsible for reuptake and recycling of 5-hydroxytryptamine (5-HT; serotonin) after its exocytotic release during neurotransmission. Mutations in human SERT are associated with psychiatric disorders and autism. Some of these mutations affect the regulation of SERT activity by cGMP-dependent phosphorylation. Here we provide direct evidence that this phosphorylation occurs at Thr276, predicted to lie near the cytoplasmic end of transmembrane helix 5 (TM5). Using membranes from HeLa cells expressing SERT and intact rat basophilic leukemia cells, we show that agents such as Na(+) and cocaine that stabilize outward-open conformations of SERT decreased phosphorylation and agents that stabilize inward-open conformations (e.g., 5-HT, ibogaine) increased phosphorylation. The opposing effects of the inhibitors cocaine and ibogaine were each reversed by an excess of the other inhibitor. Inhibition of phosphorylation by Na(+) and stimulation by ibogaine occurred at concentrations that induced outward opening and inward opening, respectively, as measured by the accessibility of cysteine residues in the extracellular and cytoplasmic permeation pathways, respectively. The results are consistent with a mechanism of SERT regulation that is activated by the transport of 5-HT, which increases the level of inward-open SERT and may lead to unwinding of the TM5 helix to allow phosphorylation.

  5. Control of serotonin transporter phosphorylation by conformational state

    PubMed Central

    Zhang, Yuan-Wei; Turk, Benjamin E.

    2016-01-01

    Serotonin transporter (SERT) is responsible for reuptake and recycling of 5-hydroxytryptamine (5-HT; serotonin) after its exocytotic release during neurotransmission. Mutations in human SERT are associated with psychiatric disorders and autism. Some of these mutations affect the regulation of SERT activity by cGMP-dependent phosphorylation. Here we provide direct evidence that this phosphorylation occurs at Thr276, predicted to lie near the cytoplasmic end of transmembrane helix 5 (TM5). Using membranes from HeLa cells expressing SERT and intact rat basophilic leukemia cells, we show that agents such as Na+ and cocaine that stabilize outward-open conformations of SERT decreased phosphorylation and agents that stabilize inward-open conformations (e.g., 5-HT, ibogaine) increased phosphorylation. The opposing effects of the inhibitors cocaine and ibogaine were each reversed by an excess of the other inhibitor. Inhibition of phosphorylation by Na+ and stimulation by ibogaine occurred at concentrations that induced outward opening and inward opening, respectively, as measured by the accessibility of cysteine residues in the extracellular and cytoplasmic permeation pathways, respectively. The results are consistent with a mechanism of SERT regulation that is activated by the transport of 5-HT, which increases the level of inward-open SERT and may lead to unwinding of the TM5 helix to allow phosphorylation. PMID:27140629

  6. Photoinduced conformational switch of enantiopure azobenzenes controlled by a sulfoxide.

    PubMed

    Carreño, M Carmen; García, Isabel; Núñez, Irene; Merino, Estíbaliz; Ribagorda, María; Pieraccini, Silvia; Spada, Gian Piero

    2007-06-06

    Two series of enantiopure azobenzenes with a p-tolylsulfoxide at the ortho or meta position with respect to the azo group, have been regioselectively synthesized. Both can act as enantiopure molecular switches showing different structural features owing to the presence of the stereogenic sulfur. The photoisomerization process, studied by UV-vis, circular dichroism (CD), NMR, and chiral HPLC evidenced a double role of the sulfoxide. A transfer of chirality from the sulfoxide to the azo system was observed by CD in both cis and trans-isomers of the meta sulfinyl derivatives 3, whereas this perturbation was evident for the ortho sulfinyl series 7 only in the cis isomer. The NMR study evidenced that the s-cis rigid conformation of the bisaromatic sulfoxide was fixing a different orientation of the overall system in each series both in the trans and cis isomers, by forcing a final U-shaped structure in cis-3 and an S-shaped structure in cis-7. Very different values of specific optical rotations were measured in both trans and cis isomers, also reflecting the existence of distinct chiral entities in the photostationary states. The easy and reversible changes occurring between different conformational states could find applications in the photocontrol of several molecular switches.

  7. 46 CFR 160.132-15 - Production inspections, tests, quality control, and conformance of davits.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 6 2012-10-01 2012-10-01 false Production inspections, tests, quality control, and... Launching Appliances-Davits § 160.132-15 Production inspections, tests, quality control, and conformance of... necessary to maintain quality control and to monitor compliance with the requirements of this subpart....

  8. 46 CFR 160.170-15 - Production inspections, tests, quality control, and conformance of release mechanisms.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., quality control, and conformance of release mechanisms. (a) Unless the Commandant directs otherwise, an...— (1) Institute a quality control procedure to ensure that all production release mechanisms are... 46 Shipping 6 2012-10-01 2012-10-01 false Production inspections, tests, quality control,...

  9. 46 CFR 160.133-15 - Production inspections, tests, quality control, and conformance of release mechanisms.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., tests, quality control, and conformance of release mechanisms. (a) Unless the Commandant directs.... The manufacturer must— (1) Institute a quality control procedure to ensure that all production release... 46 Shipping 6 2012-10-01 2012-10-01 false Production inspections, tests, quality control,...

  10. 46 CFR 160.115-15 - Production inspections, tests, quality control, and conformance of winches.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 6 2012-10-01 2012-10-01 false Production inspections, tests, quality control, and... Launching Appliances-Winches § 160.115-15 Production inspections, tests, quality control, and conformance of... necessary to maintain quality control and to monitor compliance with the requirements of this subpart....

  11. Membrane manipulations by the ESCRT machinery.

    PubMed

    Odorizzi, Greg

    2015-01-01

    The endosomal sorting complexes required for transport (ESCRTs) collectively comprise a machinery that was first known for its function in the degradation of transmembrane proteins in the endocytic pathway of eukaryotic cells. Since their discovery, however, ESCRTs have been recognized as playing important roles at the plasma membrane, which appears to be the original site of function for the ESCRT machinery. This article reviews some of the major research findings that have shaped our current understanding of how the ESCRT machinery controls membrane dynamics and considers new roles for the ESCRT machinery that might be driven by these mechanisms.

  12. Using Chemicals to Optimize Conformance Control in Fractured Reservoirs

    SciTech Connect

    Seright, R.S.

    1999-06-08

    This technical progress report describes work performed from October 1, 1998 through December 31, 1998, for the project, ''Using Chemicals to Optimize Conformance in Fractured Reservoirs.'' In our first task area, disproportionate permeability reduction, a literature survey and analysis are underway to identify options for reducing permeability to water much more than that to oil. In our second task area, we are encouraging the use of our recently developed software for sizing gelant treatments in hydraulically fractured production wells. In several field applications, we noted the importance of obtaining accurate values of the static reservoir pressure before using our program. In our third task area, we examined gel properties as they extruded through fractures. We found stable pressure gradients during injection of a large volume of a one-day-old Cr(III)-acetate-HPAM gel into a 0.04-in.-wide, four-ft-long fracture. This finding confirms that gel injection (under our specific circumstances) did not lead to continuously increasing pressure gradients and severely limited gel propagation. Our experiments also provided insights into the mechanism for gel propagation during extrusion through fractures.

  13. 46 CFR 115.804 - Machinery.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...) Operational test of the means provided for pumping bilges; and (i) Test of machinery alarms including bilge... managing operator shall be prepared to conduct tests and have the vessel ready for inspections of machinery... ahead and astern; (b) Operational test and inspection of engine control mechanisms including primary...

  14. 46 CFR 115.804 - Machinery.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...) Operational test of the means provided for pumping bilges; and (i) Test of machinery alarms including bilge... managing operator shall be prepared to conduct tests and have the vessel ready for inspections of machinery... ahead and astern; (b) Operational test and inspection of engine control mechanisms including primary...

  15. 46 CFR 115.804 - Machinery.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...) Operational test of the means provided for pumping bilges; and (i) Test of machinery alarms including bilge... managing operator shall be prepared to conduct tests and have the vessel ready for inspections of machinery... ahead and astern; (b) Operational test and inspection of engine control mechanisms including primary...

  16. 46 CFR 115.804 - Machinery.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...) Operational test of the means provided for pumping bilges; and (i) Test of machinery alarms including bilge... managing operator shall be prepared to conduct tests and have the vessel ready for inspections of machinery... ahead and astern; (b) Operational test and inspection of engine control mechanisms including primary...

  17. 46 CFR 115.804 - Machinery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...) Operational test of the means provided for pumping bilges; and (i) Test of machinery alarms including bilge... managing operator shall be prepared to conduct tests and have the vessel ready for inspections of machinery... ahead and astern; (b) Operational test and inspection of engine control mechanisms including primary...

  18. Conformational control of Cascade interference and priming activities in CRISPR immunity

    PubMed Central

    Xue, Chaoyou; Whitis, Natalie R.; Sashital, Dipali G.

    2017-01-01

    Summary During Type I-E CRISPR-Cas immunity, the Cascade surveillance complex utilizes CRISPR-derived RNAs to target complementary invasive DNA for destruction. When invader mutation blocks this interference activity, Cascade instead triggers rapid primed adaptation against the invader. The molecular basis for this dual Cascade activity is poorly understood. Here we show that the conformation of the Cse1 subunit controls Cascade activity. Using FRET, we find that Cse1 exists in a dynamic equilibrium between “open” and “closed” conformations, and the extent to which the open conformation is favored directly correlates with the attenuation of interference and relative increase in priming activity upon target mutation. Additionally, the Cse1 L1 motif modulates Cascade activity by stabilizing the closed conformation. L1 mutations promote the open conformation and switch immune response from interference to priming. Our results demonstrate that Cascade conformation controls the functional outcome of target recognition, enabling tunable CRISPR immune response to combat invader evolution. PMID:27871367

  19. Ubiquitination-dependent quality control of hERG K+ channel with acquired and inherited conformational defect at the plasma membrane.

    PubMed

    Apaja, Pirjo M; Foo, Brian; Okiyoneda, Tsukasa; Valinsky, William C; Barriere, Herve; Atanasiu, Roxana; Ficker, Eckhard; Lukacs, Gergely L; Shrier, Alvin

    2013-12-01

    Membrane trafficking in concert with the peripheral quality control machinery plays a critical role in preserving plasma membrane (PM) protein homeostasis. Unfortunately, the peripheral quality control may also dispose of partially or transiently unfolded polypeptides and thereby contribute to the loss-of-expression phenotype of conformational diseases. Defective functional PM expression of the human ether-a-go-go-related gene (hERG) K(+) channel leads to the prolongation of the ventricular action potential that causes long QT syndrome 2 (LQT2), with increased propensity for arrhythmia and sudden cardiac arrest. LQT2 syndrome is attributed to channel biosynthetic processing defects due to mutation, drug-induced misfolding, or direct channel blockade. Here we provide evidence that a peripheral quality control mechanism can contribute to development of the LQT2 syndrome. We show that PM hERG structural and metabolic stability is compromised by the reduction of extracellular or intracellular K(+) concentration. Cardiac glycoside-induced intracellular K(+) depletion conformationally impairs the complex-glycosylated channel, which provokes chaperone- and C-terminal Hsp70-interacting protein-dependent polyubiquitination, accelerated internalization, and endosomal sorting complex required for transport-dependent lysosomal degradation. A similar mechanism contributes to the down-regulation of PM hERG harboring LQT2 missense mutations, with incomplete secretion defect. These results suggest that PM quality control plays a determining role in the loss-of-expression phenotype of hERG in certain hereditary and acquired LTQ2 syndromes.

  20. 46 CFR 160.135-15 - Production inspections, tests, quality control, and conformance of lifeboats.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 6 2013-10-01 2013-10-01 false Production inspections, tests, quality control, and... (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Lifeboats (SOLAS) § 160.135-15 Production inspections, tests, quality control, and conformance of...

  1. 46 CFR 160.135-15 - Production inspections, tests, quality control, and conformance of lifeboats.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 6 2014-10-01 2014-10-01 false Production inspections, tests, quality control, and... (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Lifeboats § 160.135-15 Production inspections, tests, quality control, and conformance of lifeboats....

  2. Dizinc Lactide Polymerization Catalysts: Hyperactivity by Control of Ligand Conformation and Metallic Cooperativity

    PubMed Central

    Thevenon, Arnaud; Romain, Charles; Bennington, Michael S.; White, Andrew J. P.; Davidson, Hannah J.

    2016-01-01

    Abstract Understanding how to moderate and improve catalytic activity is critical to improving degradable polymer production. Here, di‐ and monozinc catalysts, coordinated by bis(imino)diphenylamido ligands, show remarkable activities and allow determination of the factors controlling performance. In most cases, the dizinc catalysts significantly out‐perform the monozinc analogs. Further, for the best dizinc catalyst, the ligand conformation controls activity: the catalyst with “folded” ligand conformation shows turnover frequency (TOF) values up to 60 000 h−1 (0.1 mol % loading, 298 K, [LA]=1 m), whilst that with a “planar” conformation is much slower, under similar conditions (TOF=30 h−1). Dizinc catalysts also perform very well under immortal conditions, showing improved control, and are able to tolerate loadings as low as 0.002 mol % whilst conserving high activity (TOF=12 500 h−1). PMID:27295339

  3. Conformational Transitions in Molecular Systems

    NASA Astrophysics Data System (ADS)

    Bachmann, M.; Janke, W.

    2008-11-01

    Proteins are the "work horses" in biological systems. In almost all functions specific proteins are involved. They control molecular transport processes, stabilize the cell structure, enzymatically catalyze chemical reactions; others act as molecular motors in the complex machinery of molecular synthetization processes. Due to their significance, misfolds and malfunctions of proteins typically entail disastrous diseases, such as Alzheimer's disease and bovine spongiform encephalopathy (BSE). Therefore, the understanding of the trinity of amino acid composition, geometric structure, and biological function is one of the most essential challenges for the natural sciences. Here, we glance at conformational transitions accompanying the structure formation in protein folding processes.

  4. Sequence-independent Control of Peptide Conformation in Liposomal Vaccines for Targeting Protein Misfolding Diseases*

    PubMed Central

    Hickman, David T.; López-Deber, María Pilar; Ndao, Dorin Mlaki; Silva, Alberto B.; Nand, Deepak; Pihlgren, Maria; Giriens, Valérie; Madani, Rime; St-Pierre, Annie; Karastaneva, Hristina; Nagel-Steger, Luitgard; Willbold, Dieter; Riesner, Detlev; Nicolau, Claude; Baldus, Marc; Pfeifer, Andrea; Muhs, Andreas

    2011-01-01

    Synthetic peptide immunogens that mimic the conformation of a target epitope of pathological relevance offer the possibility to precisely control the immune response specificity. Here, we performed conformational analyses using a panel of peptides in order to investigate the key parameters controlling their conformation upon integration into liposomal bilayers. These revealed that the peptide lipidation pattern, the lipid anchor chain length, and the liposome surface charge all significantly alter peptide conformation. Peptide aggregation could also be modulated post-liposome assembly by the addition of distinct small molecule β-sheet breakers. Immunization of both mice and monkeys with a model liposomal vaccine containing β-sheet aggregated lipopeptide (Palm1–15) induced polyclonal IgG antibodies that specifically recognized β-sheet multimers over monomer or non-pathological native protein. The rational design of liposome-bound peptide immunogens with defined conformation opens up the possibility to generate vaccines against a range of protein misfolding diseases, such as Alzheimer disease. PMID:21343310

  5. 46 CFR 111.103-3 - Machinery space ventilation.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Machinery space ventilation. 111.103-3 Section 111.103-3...-GENERAL REQUIREMENTS Remote Stopping Systems § 111.103-3 Machinery space ventilation. (a) Each machinery space ventilation system must have two controls to stop the ventilation, one of which may be the supply...

  6. 46 CFR 111.103-3 - Machinery space ventilation.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Machinery space ventilation. 111.103-3 Section 111.103-3...-GENERAL REQUIREMENTS Remote Stopping Systems § 111.103-3 Machinery space ventilation. (a) Each machinery space ventilation system must have two controls to stop the ventilation, one of which may be the supply...

  7. 46 CFR 111.103-3 - Machinery space ventilation.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 4 2014-10-01 2014-10-01 false Machinery space ventilation. 111.103-3 Section 111.103-3...-GENERAL REQUIREMENTS Remote Stopping Systems § 111.103-3 Machinery space ventilation. (a) Each machinery space ventilation system must have two controls to stop the ventilation, one of which may be the supply...

  8. 46 CFR 111.103-3 - Machinery space ventilation.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Machinery space ventilation. 111.103-3 Section 111.103-3...-GENERAL REQUIREMENTS Remote Stopping Systems § 111.103-3 Machinery space ventilation. (a) Each machinery space ventilation system must have two controls to stop the ventilation, one of which may be the...

  9. 46 CFR 111.103-3 - Machinery space ventilation.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Machinery space ventilation. 111.103-3 Section 111.103-3...-GENERAL REQUIREMENTS Remote Stopping Systems § 111.103-3 Machinery space ventilation. (a) Each machinery space ventilation system must have two controls to stop the ventilation, one of which may be the...

  10. The transcriptional control machinery as well as the cell wall integrity and its regulation are involved in the detoxification of the organic solvent dimethyl sulfoxide in Saccharomyces cerevisiae.

    PubMed

    Zhang, Lilin; Liu, Ningning; Ma, Xiao; Jiang, Linghuo

    2013-03-01

    In the present study, we have identified 339 dimethyl sulfoxide (DMSO)-sensitive and nine DMSO-tolerant gene mutations in Saccharomyces cerevisiae through a functional genomics approach. Twelve of these identified DMSO-sensitive mutations are of genes involved in the general control of gene expression mediated by the SWR1 complex and the RNA polymerase II mediator complex, whereas 71 of them are of genes involved in the protein trafficking and vacuolar sorting processes. In addition, twelve of these DMSO-sensitive mutations are of genes involved in the cell wall integrity (CWI) and its regulation. DMSO-tolerant mutations are of genes mainly involved in the metabolism and the gene expression control. Therefore, the transcriptional control machinery, the CWI and its regulation as well as the protein trafficking and sorting process play critical roles in the DMSO detoxification in yeast cells.

  11. Allosteric activation via kinetic control: Potassium accelerates a conformational change in IMP dehydrogenase†

    PubMed Central

    Riera, Thomas V.; Zheng, Lianqing; Josephine, Helen R.; Min, Donghong; Yang, Wei; Hedstrom, Lizbeth

    2011-01-01

    Allosteric activators are generally believed to shift the equilibrium distribution of enzyme conformations to favor a catalytically productive structure; the kinetics of conformational exchange is seldom addressed. Several observations suggested that the usual allosteric mechanism might not apply to the activation of IMP dehydrogenase (IMPDH) by monovalent cations. Therefore we investigated the mechanism of K+ activation in IMPDH by delineating the kinetic mechanism in the absence of monovalent cations. Surprisingly, the K+-dependence of kcat derives from the rate of flap closure, which increases by ≥65-fold in the presence of K+. We performed both alchemical free energy simulations and potential of mean force calculations using the orthogonal space random walk strategy to computationally analyze how K+ accelerates this conformational change. The simulations recapitulate the preference of IMPDH for K+, validating the computational models. When K+ is replaced with a dummy ion, the residues of the K+ binding site relax into ordered secondary structure, creating a barrier to conformational exchange. K+ mobilizes these residues by providing alternate interactions for the main chain carbonyls. Potential of mean force calculations indicate that K+ changes the shape of the energy well, shrinking the reaction coordinate by shifting the closed conformation toward the open state. This work suggests that allosteric regulation can be under kinetic as well as thermodynamic control. PMID:21870820

  12. A nucleotide-controlled conformational switch modulates the activity of eukaryotic IMP dehydrogenases.

    PubMed

    Buey, Rubén M; Fernández-Justel, David; Marcos-Alcalde, Íñigo; Winter, Graeme; Gómez-Puertas, Paulino; de Pereda, José María; Luis Revuelta, José

    2017-06-01

    Inosine-5'-monophosphate dehydrogenase (IMPDH) is an essential enzyme for nucleotide metabolism and cell proliferation. Despite IMPDH is the target of drugs with antiviral, immunosuppressive and antitumor activities, its physiological mechanisms of regulation remain largely unknown. Using the enzyme from the industrial fungus Ashbya gossypii, we demonstrate that the binding of adenine and guanine nucleotides to the canonical nucleotide binding sites of the regulatory Bateman domain induces different enzyme conformations with significantly distinct catalytic activities. Thereby, the comparison of their high-resolution structures defines the mechanistic and structural details of a nucleotide-controlled conformational switch that allosterically modulates the catalytic activity of eukaryotic IMPDHs. Remarkably, retinopathy-associated mutations lie within the mechanical hinges of the conformational change, highlighting its physiological relevance. Our results expand the mechanistic repertoire of Bateman domains and pave the road to new approaches targeting IMPDHs.

  13. Protein conformation as a regulator of cell-matrix adhesion.

    PubMed

    Hytönen, Vesa P; Wehrle-Haller, Bernhard

    2014-04-14

    The dynamic regulation of cell-matrix adhesion is essential for tissue homeostasis and architecture, and thus numerous pathologies are linked to altered cell-extracellular matrix (ECM) interaction and ECM scaffold. The molecular machinery involved in cell-matrix adhesion is complex and involves both sensory and matrix-remodelling functions. In this review, we focus on how protein conformation controls the organization and dynamics of cell-matrix adhesion. The conformational changes in various adhesion machinery components are described, including examples from ECM as well as cytoplasmic proteins. The discussed mechanisms involved in the regulation of protein conformation include mechanical stress, post-translational modifications and allosteric ligand-binding. We emphasize the potential role of intrinsically disordered protein regions in these processes and discuss the role of protein networks and co-operative protein interactions in the formation and consolidation of cell-matrix adhesion and extracellular scaffolds.

  14. SLC38A9 is a component of the lysosomal amino acid-sensing machinery that controls mTORC1

    PubMed Central

    Rebsamen, Manuele; Pochini, Lorena; Stasyk, Taras; de Araújo, Mariana E. G.; Galluccio, Michele; Kandasamy, Richard K.; Snijder, Berend; Fauster, Astrid; Rudashevskaya, Elena L.; Bruckner, Manuela; Scorzoni, Stefania; Filipek, Przemyslaw A.; Huber, Kilian V. M.; Bigenzahn, Johannes; Heinz, Leonhard X.; Kraft, Claudine; Bennett, Keiryn L.; Indiveri, Cesare; Huber, Lukas A.; Superti-Furga, Giulio

    2014-01-01

    Cell growth and proliferation are tightly linked to nutrient availability. The mechanistic target of rapamycin complex 1 (mTORC1) integrates the presence of growth factors, energy levels, glucose and amino acids to modulate metabolic status and cellular responses1-3. mTORC1 is activated at the surface of lysosomes by the RAG GTPases and the Ragulator complex through a not fully understood mechanism monitoring amino acid availability in the lysosomal lumen and involving the vacuolar H+ -ATPase 4-8. Here we describe the uncharacterized human member 9 of the solute carrier family 38 (SLC38A9) as a lysosomal membrane-resident protein competent in amino acid transport. Extensive functional proteomic analysis established SLC38A9 as an integral part of the Ragulator/RAG GTPases machinery. Gain of SLC38A9 function rendered cells resistant to amino acid withdrawal, while loss of SLC38A9 expression impaired amino acid-induced mTORC1 activation. Thus SLC38A9 is a physical and functional component of the amino acid-sensing machinery that controls the activation of mTOR. PMID:25561175

  15. The RNAi machinery controls distinct responses to environmental signals in the basal fungus Mucor circinelloides

    SciTech Connect

    Nicolas, Francisco E.; Vila, Ana; Moxon, Simon; Cascales, Maria D.; Torres-Martinez, Santiago; Ruiz-Vazquez, Rosa M.; Garre, Victoriano

    2015-03-25

    Here, RNA interference (RNAi) is a conserved mechanism of genome defence that can also have a role in the regulation of endogenous functions through endogenous small RNAs (esRNAs). In fungi, knowledge of the functions regulated by esRNAs has been hampered by lack of clear phenotypes in most mutants affected in the RNAi machinery. Mutants of Mucor circinelloides affected in RNAi genes show defects in physiological and developmental processes, thus making Mucor an outstanding fungal model for studying endogenous functions regulated by RNAi. Some classes of Mucor esRNAs map to exons (ex-siRNAs) and regulate expression of the genes from which they derive. To have a broad picture of genes regulated by the silencing machinery during vegetative growth, we have sequenced and compared the mRNA profiles of mutants in the main RNAi genes by using RNA-seq. In addition, we have achieved a more complete phenotypic characterization of silencing mutants Deletion of any main RNAi gene provoked a deep impact in mRNA accumulation at exponential and stationary growth. Genes showing increased mRNA levels, as expected for direct ex-siRNAs targets, but also genes with decreased expression were detected, suggesting that, most probably, the initial ex-siRNA targets regulate the expression of other genes, which can be up- or down-regulated. Expression of 50% of the genes was dependent on more than one RNAi gene in agreement with the existence of several classes of ex-siRNAs produced by different combinations of RNAi proteins. These combinations of proteins have also been involved in the regulation of different cellular processes. Besides genes regulated by the canonical RNAi pathway, this analysis identified processes, such as growth at low pH and sexual interaction that are regulated by a dicer-independent non-canonical RNAi pathway. In conclusion, this work shows that the RNAi pathways play a relevant role in the regulation of a significant number of endogenous

  16. The HSP90 chaperone machinery.

    PubMed

    Schopf, Florian H; Biebl, Maximilian M; Buchner, Johannes

    2017-06-01

    The heat shock protein 90 (HSP90) chaperone machinery is a key regulator of proteostasis under both physiological and stress conditions in eukaryotic cells. As HSP90 has several hundred protein substrates (or 'clients'), it is involved in many cellular processes beyond protein folding, which include DNA repair, development, the immune response and neurodegenerative disease. A large number of co-chaperones interact with HSP90 and regulate the ATPase-associated conformational changes of the HSP90 dimer that occur during the processing of clients. Recent progress has allowed the interactions of clients with HSP90 and its co-chaperones to be defined. Owing to the importance of HSP90 in the regulation of many cellular proteins, it has become a promising drug target for the treatment of several diseases, which include cancer and diseases associated with protein misfolding.

  17. Dynamic and Progressive Control of DNA Origami Conformation by Modulating DNA Helicity with Chemical Adducts.

    PubMed

    Chen, Haorong; Zhang, Hanyu; Pan, Jing; Cha, Tae-Gon; Li, Shiming; Andréasson, Joakim; Choi, Jong Hyun

    2016-05-24

    DNA origami has received enormous attention for its ability to program complex nanostructures with a few nanometer precision. Dynamic origami structures that change conformation in response to environmental cues or external signals hold great promises in sensing and actuation at the nanoscale. The reconfiguration mechanism of existing dynamic origami structures is mostly limited to single-stranded hinges and relies almost exclusively on DNA hybridization or strand displacement. Here, we show an alternative approach by demonstrating on-demand conformation changes with DNA-binding molecules, which intercalate between base pairs and unwind DNA double helices. The unwinding effect modulates the helicity mismatch in DNA origami, which significantly influences the internal stress and the global conformation of the origami structure. We demonstrate the switching of a polymerized origami nanoribbon between different twisting states and a well-constrained torsional deformation in a monomeric origami shaft. The structural transformation is shown to be reversible, and binding isotherms confirm the reconfiguration mechanism. This approach provides a rapid and reversible means to change DNA origami conformation, which can be used for dynamic and progressive control at the nanoscale.

  18. Entropy and barrier-controlled fluctuations determine conformational viscoelasticity of single biomolecules.

    PubMed

    Khatri, Bhavin S; Kawakami, Masaru; Byrne, Katherine; Smith, D Alastair; McLeish, Tom C B

    2007-03-15

    Biological macromolecules have complex and nontrivial energy landscapes, endowing them with a unique conformational adaptability and diversity in function. Hence, understanding the processes of elasticity and dissipation at the nanoscale is important to molecular biology and emerging fields such as nanotechnology. Here we analyze single molecule fluctuations in an atomic force microscope, using a generic model of biopolymer viscoelasticity that includes local "internal" conformational dissipation. Comparing two biopolymers, dextran and cellulose (polysaccharides with and without local bistable transitions), demonstrates that signatures of simple conformational change are minima in both the elastic and internal friction constants around a characteristic force. A novel analysis of dynamics on a bistable energy landscape provides a simple explanation: an elasticity driven by the entropy, and friction by a barrier-controlled hopping time of populations between states, which is surprisingly distinct to the well-known relaxation time. This nonequilibrium microscopic analysis thus provides a means of quantifying new dynamical features of the energy landscape of the glucopyranose ring, revealing an unexpected underlying roughness and information on the shape of the barrier of the chair-boat transition in dextran. The results presented herein provide a basis toward probing the viscoelasticity of macromolecular conformational transitions on more complex energy landscapes, such as during protein folding.

  19. Principles and applications of a controllable electromagnetic band gap material to a conformable spherical radome

    NASA Astrophysics Data System (ADS)

    Haché, S.; Burokur, S. N.; de Lustrac, A.; Gadot, F.; Cailleu, P.; Piau, G.-P.

    2009-06-01

    This paper presents the principle of two types of conformable and controllable spherical radome based on Electromagnetic Band Gap (EBG) materials operating at around 10 GHz. The EBG structure is composed of a grid of metallic wires conformed on a hollow spherical object. Two switching control configurations are considered: (1) between an EBG structure made of electrically continuous wires and another one made of discontinuous wires, and (2) between two EBG structures made of discontinuous wires where each has a different period of discontinuities. Both switching configurations are simulated and experimentally characterized on passive prototypes. An excellent agreement is observed between simulations and measurements. The radiation patterns of two types of antennas, a horn antenna and a meteorological antenna, are also measured in the presence of the radome.

  20. Probing Conformational Change of Bovine Serum Albumin–Dextran Conjugates under Controlled Dry Heating

    SciTech Connect

    Xia, Shuqin; Li, Yunqi; Zhao, Qin; Li, Ji; Xia, Qiuyang; Zhang, Xiaoming; Huang, Qingrong

    2015-04-29

    The time-dependent conformational change of bovine serum album (BSA) during Maillard reaction with dextran under controlled dry heating has been studied by small-angle X-ray scattering, fluorescence spectroscopy, dynamic light scattering, and circular dichroism analysis. Through the research on the radii of gyration (Rg), intrinsic fluorescence, and secondary structure, conjugates with dextran coating were found to inhibit BSA aggregation and preserve the secondary structure of native BSA against long-time heat treatment during Maillard reaction. The results suggested that the hydrophilic dextran was conjugated to the compact protein surface and enclosed it and more dextran chains were attached to BSA with the increase of the heating time. The study presented here will be beneficial to the understanding of the conformational evolution of BSA molecules during the dry-heating Maillard reaction and to the control of the protein–polysaccharide conjugate structure.

  1. Color deviation controlling of phosphor conformal coating by advanced spray painting technology for white LEDs.

    PubMed

    Yang, Liang; Wang, Simin; Lv, Zhicheng; Liu, Sheng

    2013-04-01

    An advanced phosphor conformal coating technology is proposed, good correlated color temperature (CCT) and chromaticity uniformity samples are fabricated through phosphor spray painting technology. Spray painting technology is also suitable for phosphor conformal coating of whole LED wafers. The samples of different CCTs are obtained through controlling the phosphor film thickness in the range of 6-80 μm; CCT variation of samples can be controlled in the range of ±200 K. The experimental Δuv reveals that the spray painting method can obtain a much smaller CCT variation (Δuv of 1.36e(-3)) than the conventional dispensing method (Δuv of 11.86e(-3)) when the light is emitted at angles from -90° to +90°, and chromaticity area uniformity is also improved significantly.

  2. Probing Conformational Change of Bovine Serum Albumin-Dextran Conjugates under Controlled Dry Heating.

    PubMed

    Xia, Shuqin; Li, Yunqi; Zhao, Qin; Li, Ji; Xia, Qiuyang; Zhang, Xiaoming; Huang, Qingrong

    2015-04-29

    The time-dependent conformational change of bovine serum album (BSA) during Maillard reaction with dextran under controlled dry heating has been studied by small-angle X-ray scattering, fluorescence spectroscopy, dynamic light scattering, and circular dichroism analysis. Through the research on the radii of gyration (Rg), intrinsic fluorescence, and secondary structure, conjugates with dextran coating were found to inhibit BSA aggregation and preserve the secondary structure of native BSA against long-time heat treatment during Maillard reaction. The results suggested that the hydrophilic dextran was conjugated to the compact protein surface and enclosed it and more dextran chains were attached to BSA with the increase of the heating time. The study presented here will be beneficial to the understanding of the conformational evolution of BSA molecules during the dry-heating Maillard reaction and to the control of the protein-polysaccharide conjugate structure.

  3. Multi-state targeting machinery govern the fidelity and efficiency of protein localization.

    PubMed

    Yang, Mingjun; Pang, Xueqin; Han, Keli

    2014-01-01

    Proper localization of newly synthesized proteins is essential to cellular function. Among different protein localization modes, the signal recognition particle (SRP) and SRP receptor (SR) constitute the conserved targeting machinery in all three life kingdoms and mediate about one third of the protein targeting reactions. Based on experimental and computational studies, a detailed molecular model is proposed to explain how this molecular machinery governs the efficiency and fidelity of protein localizations. In this targeting machinery, two distinct SRP GTPases are contained into the SRP and SR that are responsible to the interactions between SRP and SR. These two GTPases can interact with one another through a series of sequential and discrete interaction states that are the early intermediate formation, stable complex association, and GTPase activation. In contrast to canonical GTPases, a floppy and open conformation adopted in free SRP GTPases can facilitate efficient GTP/GDP exchange without the aid of any external factors. As the apo-form free SRP GTPases can adopt the conformational states of GDP- or GTP-bound form, the binding of GTP/GDP follows a mechanism of conformational selection. In the first step of complex formation, the two SRP GTPases can rapidly assemble into an unstable early intermediate by selecting and stabilizing one another's primed states from the equilibrium conformational ensemble. Subsequently, extensive inter- and intra-domain changes rearrange the early complex into a tight and closed state of stable complex through induced fit mechanism. Upon stable complex association, further tune of several important interaction networks activates the SRP GTPase for GTP hydrolysis. These different conformational states are coupled to corresponding protein targeting events, in which the complex formation deliveries the translating ribosome to the target membrane and the GTPase activation couples to the cargo release from SRP-SR machinery to the

  4. Active feedback control for stabilization of vibration in rotating machinery (24. 034). Period covered: April 1-June 30, 1980

    SciTech Connect

    1980-01-01

    Some of the considerations involved in the use of feedback control as a means of reducing the unbalanced response of a rotor or of eliminating or alleviating rotor dynamic instability are discussed. A simple model of a mass on a flexible shaft is used to illustrate the application of feedback control concepts. A description is given of a system assembled at the University of Virginia which uses feedback control individually adjustable in the vertical and horizontal directions to support the shaft bearings.

  5. Agriculture Education. Farm Machinery.

    ERIC Educational Resources Information Center

    Stuttgart Public Schools, AR.

    This curriculum guide is designed for group instruction of secondary agricultural education students enrolled in one or two semester-long courses in farm machinery. The guide presents units of study in the following areas: (1) small gas engines, (2) job opportunities, (3) tractors, (4) engines, (5) hydraulics, (6) electrical system, (7) combine…

  6. Agriculture Power and Machinery.

    ERIC Educational Resources Information Center

    Rogers, Tom

    This guide is intended to assist vocational agriculture teachers who are teaching secondary- or postsecondary-level courses in agricultural power and machinery. The materials presented are based on the Arizona validated occupational competencies and tasks for the following occupations: service manager, shop foreman, service technician, and tractor…

  7. Agriculture Power and Machinery.

    ERIC Educational Resources Information Center

    Rogers, Tom

    This guide is intended to assist vocational agriculture teachers who are teaching secondary- or postsecondary-level courses in agricultural power and machinery. The materials presented are based on the Arizona validated occupational competencies and tasks for the following occupations: service manager, shop foreman, service technician, and tractor…

  8. Targeting Proteostasis Through the Protein Quality Control Function of the Hsp90/Hsp70-based Chaperone Machinery for Treatment of Adult Onset Neurodegenerative Diseases

    PubMed Central

    Pratt, William B.; Gestwicki, Jason E.; Osawa, Yoichi; Lieberman, Andrew P.

    2015-01-01

    Currently available therapies for adult onset neurodegenerative diseases provide symptomatic relief, but are not disease modifying. We explore here a new neuroprotective approach based on drugs targeting chaperone-directed protein quality control. Critical target proteins that unfold and aggregate in these diseases, such as the polylglutamine androgen receptor (spinal and bulbar muscular atrophy), huntingtin (Huntington’s disease), α-synuclein (Parkinson’s disease) and tau (Alzheimer’s disease) are client proteins of Hsp90, and their turnover is regulated by the protein quality control function of the Hsp90/Hsp70-based chaperone machinery. In protein quality control Hsp90 and Hsp70 have opposing effects on client protein stability; Hsp90 stabilizes the clients and inhibits their ubiquitination, whereas Hsp70 promotes CHIP-dependent ubiquitination and proteasomal degradation. We discuss how drugs that modulate proteostasis by inhibiting Hsp90 function or by promoting Hsp70 function enhance the degradation of the critical aggregating proteins and ameliorate toxic symptoms in cell and animal disease models. PMID:25292434

  9. A prognostic scoring system for locoregional control in nasopharyngeal carcinoma following conformal radiotherapy

    SciTech Connect

    Cheng, S.H.; Tsai, S.Y.; Horng, C.-F.; Yen, K.L.; Jian, James J.; Chan, Kwan-Yee; Lin, C.-Y.; Terng, S.-D.; Tsou, M.-H.; Chu, N.-M.; Chen, H.-H.; Hsieh, C.-I.; Tan, T.-D.; Chen, P.-L.; Chung, Y.L.; Huang, Andrew T. |

    2006-11-15

    Purpose: This study established a prognostic scoring system for nasopharyngeal carcinoma (NPC), which estimates the probability of locoregional (LR) control following definitive conformal radiotherapy. Methods and Materials: Patients with nondisseminated NPC at initial presentation (n = 630) were enrolled in this study. All patients had magnetic resonance imaging of the head and neck and were treated with conformal radiotherapy. Among them, 93% had concurrent chemotherapy, and 76% had postradiation chemotherapy. The extent of the primary tumor, age at diagnosis, primary tumor size, tumor and nodal classification, histology, and serum lactate dehydrogenase (LDH) level before treatment were included in the analysis for building a prognostic scoring system. The end point for this study was LR control. Results: The prognostic score was defined as the number of adverse prognostic factors present at diagnosis. Four factors had similarly independent prognostic effects (hazard ratio, 2.0-2.6): age >40 years, histologic WHO type I-II, serum LDH level {>=}410 U/L, and involvement of two or more sites of the following anatomic structures, i.e., sphenoid floor, clivus marrow, clivus cortex, prevertebral muscles, and petrous bone. The score predicted the 5-year probability of LR control as follows: 0 (15% of the patients), 100%; 1 (42% of the patients), 93%; 2 (29% of the patients), 83%; 3 or higher (13% of the patients), 71%. Conclusion: This scoring system is useful in the decision-making for individual patients and the design of clinical trials to improve LR control for advanced-stage NPC.

  10. Machinery vibration: Origins, impressions and cures

    SciTech Connect

    Haq, I. )

    1995-01-01

    The current trend toward high performance (speed, power, flow, etc.) and low eight are causing new machinery dynamics problems. Vibration diagnostics engineering of rotor-bearing-casing systems must consider both internal and external influences to effectively predict and diagnose these problems. It is assumed that machinery vibration data are free from ambiguity, error, conform to a standard and clearly identify the physical cause(s) responsible for vibration. Rotor vibration due to internal forces are described: unbalance force characteristics; response characteristics; and rules of rotor fundamental response. Rotor vibration due to external forces include: rotating aerodynamic stall; oil whirl; oil whip; structural resonance; vane/blade passing vibration; misalignment; rotor rubbing; gear mesh vibrations; and shaft crack. These are also discussed.

  11. Cofactor-mediated conformational control in the bifunctional kinase/RNase Ire1

    PubMed Central

    2011-01-01

    Background Ire1 is a signal transduction protein in the endoplasmic reticulum (ER) membrane that serves to adjust the protein-folding capacity of the ER according to the needs of the cell. Ire1 signals, in a transcriptional program, the unfolded protein response (UPR) via the coordinated action of its protein kinase and RNase domains. In this study, we investigated how the binding of cofactors to the kinase domain of Ire1 modulates its RNase activity. Results Our results suggest that the kinase domain of Ire1 initially binds cofactors without activation of the RNase domain. RNase is activated upon a subsequent conformational rearrangement of Ire1 governed by the chemical properties of bound cofactors. The conformational step can be selectively inhibited by chemical perturbations of cofactors. Substitution of a single oxygen atom in the terminal β-phosphate group of a potent cofactor ADP by sulfur results in ADPβS, a cofactor that binds to Ire1 as well as to ADP but does not activate RNase. RNase activity can be rescued by thiophilic metal ions such as Mn2+ and Cd2+, revealing a functional metal ion-phosphate interaction which controls the conformation and RNase activity of the Ire1 ADP complex. Mutagenesis of the kinase domain suggests that this rearrangement involves movement of the αC-helix, which is generally conserved among protein kinases. Using X-ray crystallography, we show that oligomerization of Ire1 is sufficient for placing the αC-helix in the active, cofactor-bound-like conformation, even in the absence of cofactors. Conclusions Our structural and biochemical evidence converges on a model that the cofactor-induced conformational change in Ire1 is coupled to oligomerization of the receptor, which, in turn, activates RNase. The data reveal that cofactor-Ire1 interactions occur in two independent steps: binding of a cofactor to Ire1 and subsequent rearrangement of Ire1 resulting in its self-association. The pronounced allosteric effect of cofactors on

  12. Substituent effects that control conjugated oligomer conformation through non-covalent interactions

    DOE PAGES

    Sharber, Seth A.; Baral, Rom Nath; Frausto, Fanny; ...

    2017-03-31

    Although understanding the conformations and arrangements of conjugated materials as solids is key to their prospective applications, predictive power over these structural factors remains elusive. In this work, substituent effects tune non-covalent interactions between side-chain fluorinated benzyl esters and main-chain terminal arenes, in turn controlling the conformations and interchromophore aggregation of three-ring phenylene-ethynylenes (PEs). Cofacial fluoroarene–arene (ArF–ArH) interactions cause twisting in the PE backbone, interrupting intramolecular conjugation as well as blocking chromophore aggregation, both of which prevent the typically observed bathochromic shift observed upon transitioning PEs from solution to solid. This work highlights two structural factors that determine whether themore » ArF–ArH interactions, and the resulting twisted, unaggregated chromophores, occur in these solids: (i) the electron-releasing characteristic of substituents on ArH, with more electron-releasing character favoring ArF–ArH interactions, and (ii) the fluorination pattern of the ArF ring, with 2,3,4,5,6-pentafluorophenyl favoring ArF–ArH interactions over 2,4,6-trifluorophenyl. Furthermore, these trends indicate that considerations of electrostatic complementarity, whether through a polar-π or substituent–substituent mechanism, can serve as an effective design principle in controlling the interaction strengths, and therefore the optoelectronic properties, of these molecules as solids.« less

  13. Proposal for a new mass distribution control system and its simulation for vibration reduction on rotating machinery

    NASA Astrophysics Data System (ADS)

    Enginoglu, Ozan; Ozturk, Hasan

    2016-12-01

    This study presents a new mass distribution control system (MDCS) along with its analysis and simulation. It is aimed to balance a system containing rotating parts in order to minimize the dynamic vibration on it. For this purpose, a test mechanism rotating with an angular velocity of ω is simulated. The mechanism consists of a pair of MDCS, each containing three flaps connected to the shaft. The flaps rotate in relation to the shaft's plane of rotation. The center of gravity (COG) of the MDCS is concentric with the shaft axis when all three flaps are stretched out but the COG changes as the flaps rotate. By adjusting the orientations of the flaps in both systems, it is possible to create a counterforce which suppresses the imbalance force, reducing the vibration to a minimum.

  14. The RNA polymerase I transcription machinery.

    PubMed

    Russell, Jackie; Zomerdijk, Joost C B M

    2006-01-01

    The rRNAs constitute the catalytic and structural components of the ribosome, the protein synthesis machinery of cells. The level of rRNA synthesis, mediated by Pol I (RNA polymerase I), therefore has a major impact on the life and destiny of a cell. In order to elucidate how cells achieve the stringent control of Pol I transcription, matching the supply of rRNA to demand under different cellular growth conditions, it is essential to understand the components and mechanics of the Pol I transcription machinery. In this review, we discuss: (i) the molecular composition and functions of the Pol I enzyme complex and the two main Pol I transcription factors, SL1 (selectivity factor 1) and UBF (upstream binding factor); (ii) the interplay between these factors during pre-initiation complex formation at the rDNA promoter in mammalian cells; and (iii) the cellular control of the Pol I transcription machinery.

  15. Mitochondrial Machineries for Protein Import and Assembly.

    PubMed

    Wiedemann, Nils; Pfanner, Nikolaus

    2017-03-15

    Mitochondria are essential organelles with numerous functions in cellular metabolism and homeostasis. Most of the >1,000 different mitochondrial proteins are synthesized as precursors in the cytosol and are imported into mitochondria by five transport pathways. The protein import machineries of the mitochondrial membranes and aqueous compartments reveal a remarkable variability of mechanisms for protein recognition, translocation, and sorting. The protein translocases do not operate as separate entities but are connected to each other and to machineries with functions in energetics, membrane organization, and quality control. Here, we discuss the versatility and dynamic organization of the mitochondrial protein import machineries. Elucidating the molecular mechanisms of mitochondrial protein translocation is crucial for understanding the integration of protein translocases into a large network that controls organelle biogenesis, function, and dynamics. Expected final online publication date for the Annual Review of Biochemistry Volume 86 is June 20, 2017. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  16. pH-dependent transient conformational states control optical properties in cyan fluorescent protein.

    PubMed

    Laricheva, Elena N; Goh, Garrett B; Dickson, Alex; Brooks, Charles L

    2015-03-04

    (namely, local solvation at the deprotonation site and a partial flexibility of the protein β-barrel structure) and provide the first evidence that transient conformational states can control optical properties of fluorescent proteins.

  17. Allosteric Regulation Points Control the Conformational Dynamics of the Molecular Chaperone Hsp90.

    PubMed

    Rehn, Alexandra; Moroni, Elisabetta; Zierer, Bettina K; Tippel, Franziska; Morra, Giulia; John, Christine; Richter, Klaus; Colombo, Giorgio; Buchner, Johannes

    2016-11-06

    Heat shock protein 90 (Hsp90) is an ATP-dependent molecular chaperone responsible for the activation, maturation, and trafficking of several hundred client proteins in the cell. It is well known that (but not understood how) residues far away from Hsp90's nucleotide binding pocket can regulate its ATPase activity, a phenomenon called allosteric regulation. Here, the computational design of allosteric mutations was combined with in vitro and in vivo experiments to unravel nucleotide-responsive hot spots in the regulation of Hsp90. With this approach, we identified both activating and inhibiting regulation points and show that changes in those amino acids affect the conformational dynamics and ATPase activity of Hsp90 in vitro. Our observations that activating mutations loosen and inhibiting mutations rigidify the protein explain for the first time how Hsp90 changes in response to allosteric mutations. Additionally, mutations of these allosteric regulation points can be controlled by the interplay with Hsp90 co-chaperones, thus providing cells with an efficient mechanism of modifying Hsp90's intrinsic properties via different layers of regulation. Altogether, our results show that a framework for transmitting conformational information exists in the Hsp90 structure. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Salt bridge dynamics control substrate-induced conformational change in the membrane transporter GlpT

    PubMed Central

    Law, Christopher J.; Almqvist, Jonas; Bernstein, Adam; Goetz, Regina M.; Huang, Yafei; Soudant, Celine; Laaksonen, Aatto; Hovmöller, Sven; Wang, Da-Neng

    2008-01-01

    Summary Active transport of substrates across cytoplasmic membranes is of great physiological, medical and pharmaceutical importance. The glycerol-3-phosphate (G3P) transporter (GlpT) of the E. coli inner membrane is a secondary active antiporter from the ubiquitous major facilitator superfamily that couples the import of G3P to the efflux of inorganic phosphate (Pi) down its concentration gradient. Integrating information from a novel combination of structural, molecular dynamics simulations and biochemical studies, we identify the residues involved directly in binding of substrate to the inward-facing conformation of GlpT, thus defining the structural basis for the substrate-specificity of this transporter. The substrate binding mechanism involves protonation of a histidine residue at the binding site. Furthermore, our data suggest that the formation and breaking of inter- and intradomain salt bridges control the conformational change of the transporter that accompanies substrate translocation across the membrane. The mechanism we propose may be a paradigm for organophosphate/phosphate antiporters. PMID:18395745

  19. Globin domain interactions control heme pocket conformation and oligomerization of globin coupled sensors.

    PubMed

    Rivera, Shannon; Burns, Justin L; Vansuch, Gregory E; Chica, Bryant; Weinert, Emily E

    2016-11-01

    Globin coupled sensors (GCS) are O2-sensing proteins used by bacteria to monitor the surrounding gaseous environment. To investigate the biphasic O2 dissociation kinetics observed for full-length GCS proteins, isolated globin domains from Pectobacterium carotovorum ssp. carotovorum (PccGlobin), and Bordetella pertussis (BpeGlobin), have been characterized. PccGlobin is found to be dimeric, while BpeGlobin is monomeric, indicating key differences in the globin domain dimer interface. Through characterization of wild type globin domains and globin variants with mutations at the dimer interface and within the distal pocket, dimerization of the globin domain is demonstrated to correlate with biphasic dissociation kinetics. Furthermore, a distal pocket tyrosine is identified as the primary hydrogen bond donor, while a secondary hydrogen bond donor within the distal heme pocket is involved in conformation(s) that lead to the second O2 dissociation rate. These findings highlight the role of the globin dimer interface in controlling properties of both the heme pocket and full-length GCS proteins.

  20. Conformational control of DNA target cleavage by CRISPR-Cas9.

    PubMed

    Sternberg, Samuel H; LaFrance, Benjamin; Kaplan, Matias; Doudna, Jennifer A

    2015-11-05

    Cas9 is an RNA-guided DNA endonuclease that targets foreign DNA for destruction as part of a bacterial adaptive immune system mediated by clustered regularly interspaced short palindromic repeats (CRISPR). Together with single-guide RNAs, Cas9 also functions as a powerful genome engineering tool in plants and animals, and efforts are underway to increase the efficiency and specificity of DNA targeting for potential therapeutic applications. Studies of off-target effects have shown that DNA binding is far more promiscuous than DNA cleavage, yet the molecular cues that govern strand scission have not been elucidated. Here we show that the conformational state of the HNH nuclease domain directly controls DNA cleavage activity. Using intramolecular Förster resonance energy transfer experiments to detect relative orientations of the Cas9 catalytic domains when associated with on- and off-target DNA, we find that DNA cleavage efficiencies scale with the extent to which the HNH domain samples an activated conformation. We furthermore uncover a surprising mode of allosteric communication that ensures concerted firing of both Cas9 nuclease domains. Our results highlight a proofreading mechanism beyond initial protospacer adjacent motif (PAM) recognition and RNA-DNA base-pairing that serves as a final specificity checkpoint before DNA double-strand break formation.

  1. Conformational control of DNA target cleavage by CRISPR–Cas9

    PubMed Central

    Sternberg, Samuel H.; LaFrance, Benjamin; Kaplan, Matias; Doudna, Jennifer A.

    2015-01-01

    Cas9 is an RNA-guided DNA endonuclease that targets foreign DNA for destruction as part of a bacterial adaptive immune system mediated by CRISPR (clustered regularly interspaced short palindromic repeats)1,2. Together with single-guide RNAs (sgRNA)3, Cas9 also functions as a powerful genome engineering tool in plants and animals4–6, and efforts are underway to increase the efficiency and specificity of DNA targeting for potential therapeutic applications7,8. Studies of off-target effects have shown that DNA binding is far more promiscuous than DNA cleavage9–11, yet the molecular cues that govern strand scission have not been elucidated. Here we show that the conformational state of the HNH nuclease domain directly controls DNA cleavage activity. Using intramolecular Förster resonance energy transfer (FRET) experiments to detect relative orientations of the Cas9 catalytic domains when associated with on- and off-target DNA, we find that DNA cleavage efficiencies scale with the extent to which the HNH domain samples an activated conformation. We furthermore uncover a surprising mode of allosteric communication that ensures concerted firing of both Cas9 nuclease domains. Our results highlight a proofreading mechanism beyond initial PAM recognition12 and RNA–DNA base-pairing3 that serves as a final specificity checkpoint before DNA double-strand break formation. PMID:26524520

  2. Ribosome-induced changes in elongation factor Tu conformation control GTP hydrolysis

    PubMed Central

    Villa, Elizabeth; Sengupta, Jayati; Trabuco, Leonardo G.; LeBarron, Jamie; Baxter, William T.; Shaikh, Tanvir R.; Grassucci, Robert A.; Nissen, Poul; Ehrenberg, Måns; Schulten, Klaus; Frank, Joachim

    2009-01-01

    In translation, elongation factor Tu (EF-Tu) molecules deliver aminoacyl-tRNAs to the mRNA-programmed ribosome. The GTPase activity of EF-Tu is triggered by ribosome-induced conformational changes of the factor that play a pivotal role in the selection of the cognate aminoacyl-tRNAs. We present a 6.7-Å cryo-electron microscopy map of the aminoacyl-tRNA·EF-Tu·GDP·kirromycin-bound Escherichia coli ribosome, together with an atomic model of the complex obtained through molecular dynamics flexible fitting. The model reveals the conformational changes in the conserved GTPase switch regions of EF-Tu that trigger hydrolysis of GTP, along with key interactions, including those between the sarcin-ricin loop and the P loop of EF-Tu, and between the effector loop of EF-Tu and a conserved region of the 16S rRNA. Our data suggest that GTP hydrolysis on EF-Tu is controlled through a hydrophobic gate mechanism. PMID:19122150

  3. Autophagy: machinery and regulation

    PubMed Central

    Yin, Zhangyuan; Pascual, Clarence; Klionsky, Daniel J.

    2016-01-01

    Macroautophagy/autophagy is an evolutionarily conserved cellular degradation process that targets cytoplasmic materials including cytosol, macromolecules and unwanted organelles. The discovery and analysis of autophagy-related (Atg) proteins have unveiled much of the machinery of autophagosome formation. Although initially autophagy was regarded as a survival response to stress, recent studies have revealed its significance in cellular and organismal homeostasis, development and immunity. Autophagic dysfunction and dysregulation are implicated in various diseases. In this review, we briefly summarize the physiological roles, molecular mechanism, regulatory network, and pathophysiological roles of autophagy. PMID:28357331

  4. Visual Outcome and Tumor Control After Conformal Radiotherapy for Patients With Optic Nerve Sheath Meningioma

    SciTech Connect

    Arvold, Nils D.; Lessell, Simmons; Bussiere, Marc; Beaudette, Kevin; Rizzo, Joseph F.; Loeffler, Jay S.; Shih, Helen A.

    2009-11-15

    Purpose: Optic nerve sheath meningioma (ONSM) is a rare tumor that almost uniformly leads to visual dysfunction and even blindness without intervention. Because surgical extirpation carries a high risk of postoperative blindness, vision-sparing treatment strategies are desirable. Methods and Materials: We retrospectively reviewed the outcomes of 25 patients (25 optic nerves) with ONSM, treated at a single institution with conformal fractionated radiotherapy by either stereotactic photon or proton radiation. Primary endpoints were local control and visual acuity. Results: The patients presented with symptoms of visual loss (21) or orbital pain (3) or were incidentally diagnosed by imaging (3). The mean age was 44 years, and 64% were female patients. The indication for treatment was the development or progression of symptoms. Of the patients, 13 were treated with photons, 9 were treated with protons, and 3 received a combination of photons and protons. The median dose delivered was 50.4 gray equivalents (range, 45-59.4 gray equivalents). Median follow-up after radiotherapy was 30 months (range, 3-168 months), with 3 patients lost to follow-up. At most recent follow-up, 21 of 22 patients (95%) had improved (14) or stable (7) visual acuity. One patient had worsened visual acuity after initial postirradiation improvement. Of the 22 patients, 20 (95%) had no radiographic progression. Three patients had evidence of asymptomatic, limited retinopathy on ophthalmologic examination, and one had recurrent ONSM 11 years after treatment. Conclusions: Highly conformal, fractionated radiation therapy for symptomatic primary ONSM provides tumor control and improvement in visual function in most cases, with minimal treatment-induced morbidity. Longer follow-up is needed to assess the durability of tumor control and treatment-related late effects.

  5. Single-molecule spectroscopy reveals how calmodulin activates NO synthase by controlling its conformational fluctuation dynamics

    PubMed Central

    He, Yufan; Haque, Mohammad Mahfuzul; Stuehr, Dennis J.; Lu, H. Peter

    2015-01-01

    Mechanisms that regulate the nitric oxide synthase enzymes (NOS) are of interest in biology and medicine. Although NOS catalysis relies on domain motions, and is activated by calmodulin binding, the relationships are unclear. We used single-molecule fluorescence resonance energy transfer (FRET) spectroscopy to elucidate the conformational states distribution and associated conformational fluctuation dynamics of the two electron transfer domains in a FRET dye-labeled neuronal NOS reductase domain, and to understand how calmodulin affects the dynamics to regulate catalysis. We found that calmodulin alters NOS conformational behaviors in several ways: It changes the distance distribution between the NOS domains, shortens the lifetimes of the individual conformational states, and instills conformational discipline by greatly narrowing the distributions of the conformational states and fluctuation rates. This information was specifically obtainable only by single-molecule spectroscopic measurements, and reveals how calmodulin promotes catalysis by shaping the physical and temporal conformational behaviors of NOS. PMID:26311846

  6. Protein biosynthesis with conformationally restricted amino acids

    SciTech Connect

    Mendel, D. Lawrence Berkeley Lab., CA ); Ellman, J.; Schultz, P.G. )

    1993-05-19

    The incorporation of conformationally constrained amino acids into peptides is a powerful approach for generating structurally defined peptides as conformational probes and bioactive agents. The ability to site-specifically introduce constrained amino acids into large polypeptide chains would provide a similar opportunity to probe the flexibility, conformation, folding and stability of proteins. To this end, we have examined the competence of the Escherichia coli protein biosynthetic machinery to incorporate a number of these unnatural amino acids into the 164 residue protein T4 lysozyme (T4L). Results clearly demonstrate that the protein biosynthetic machinery can accommodate a wide variety of conformationally constrained amino acids. The expansion of structural motifs that can be biosynthetically incorporated into proteins to include a large number of conformationally constrained amino acids significantly increases the power of mutagenesis methods as probes of protein structure and function and provides additional insights into the steric requirements of the translational machinery. 13 refs., 2 figs.

  7. Single molecule tunneling conductance: The temperature and length dependences controlled by conformational fluctuations

    NASA Astrophysics Data System (ADS)

    Kornyshev, A. A.; Kuznetsov, A. M.

    2006-05-01

    We present a model for a tunnelling conductance of a chain molecule controlled by fluctuations of relative conformations between nearest neighbour units of the chain molecule. The model leads to a simple formula which in one regime reproduces recently reported Arrhenius dependences for alkanedithiols [W. Haiss, H. van Zalinge, D. Bethel, J. Ulstrup, D.J. Schiffrin, R.J. Nichols, Faraday Discuss. 131 (19) (2005)] with an activation energy proportional to the length of the molecule, whereas in other regimes it shows activationless behaviour corresponding to the tunnelling across more rigid molecules. The general formula covers the transition between the two limits, predicting some new dependences that could be interesting to verify experimentally.

  8. Active Vibration Dampers For Rotating Machinery

    NASA Technical Reports Server (NTRS)

    Kascack, Albert F.; Ropchock, John J.; Lakatos, Tomas F.; Montague, Gerald T.; Palazzolo, Alan; Lin, Reng Rong

    1994-01-01

    Active dampers developed to suppress vibrations in rotating machinery. Essentially feedback control systems and reciprocating piezoelectric actuators. Similar active damper containing different actuators described in LEW-14488. Concept also applicable to suppression of vibrations in stationary structures subject to winds and earthquakes. Active damper offers adjustable suppression of vibrations. Small and lightweight and responds faster to transients.

  9. Active Vibration Dampers For Rotating Machinery

    NASA Technical Reports Server (NTRS)

    Kascack, Albert F.; Ropchock, John J.; Lakatos, Tomas F.; Montague, Gerald T.; Palazzolo, Alan; Lin, Reng Rong

    1994-01-01

    Active dampers developed to suppress vibrations in rotating machinery. Essentially feedback control systems and reciprocating piezoelectric actuators. Similar active damper containing different actuators described in LEW-14488. Concept also applicable to suppression of vibrations in stationary structures subject to winds and earthquakes. Active damper offers adjustable suppression of vibrations. Small and lightweight and responds faster to transients.

  10. 46 CFR 160.156-15 - Production inspections, tests, quality control, and conformance of rescue boats and fast rescue...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 6 2014-10-01 2014-10-01 false Production inspections, tests, quality control, and..., DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND... inspections, tests, quality control, and conformance of rescue boats and fast rescue boats. (a) Unless...

  11. 46 CFR 160.156-15 - Production inspections, tests, quality control, and conformance of rescue boats and fast rescue...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 6 2013-10-01 2013-10-01 false Production inspections, tests, quality control, and..., DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND... inspections, tests, quality control, and conformance of rescue boats and fast rescue boats. (a) Unless...

  12. A computational study of vicinal fluorination in 2,3-difluorobutane: implications for conformational control in alkane chains.

    PubMed

    Fox, Stephen J; Gourdain, Stephanie; Coulthurst, Anton; Fox, Clare; Kuprov, Ilya; Essex, Jonathan W; Skylaris, Chris-Kriton; Linclau, Bruno

    2015-01-19

    A comprehensive conformational analysis of both 2,3-difluorobutane diastereomers is presented based on density functional theory calculations in vacuum and in solution, as well as NMR experiments in solution. While for 1,2-difluoroethane the fluorine gauche effect is clearly the dominant effect determining its conformation, it was found that for 2,3-difluorobutane there is a complex interplay of several effects, which are of similar magnitude but often of opposite sign. As a result, unexpected deviations in dihedral angles, relative conformational energies and populations are observed which cannot be rationalised only by chemical intuition. Furthermore, it was found that it is important to consider the free energies of the various conformers, as these lead to qualitatively different results both in vacuum and in solvent, when compared to calculations based only on the electronic energies. In contrast to expectations, it was found that vicinal syn-difluoride introduction in the butane and by extension, longer hydrocarbon chains, is not expected to lead to an effective stabilisation of the linear conformation. Our findings have implications for the use of the vicinal difluoride motif for conformational control.

  13. A conformational switch controls cell wall-remodelling enzymes required for bacterial cell division.

    PubMed

    Yang, Desirée C; Tan, Kemin; Joachimiak, Andrzej; Bernhardt, Thomas G

    2012-08-01

    Remodelling of the peptidoglycan (PG) exoskeleton is intimately tied to the growth and division of bacteria. Enzymes that hydrolyse PG are critical for these processes, but their activities must be tightly regulated to prevent the generation of lethal breaches in the PG matrix. Despite their importance, the mechanisms regulating PG hydrolase activity have remained elusive. Here we investigate the control of cell division hydrolases called amidases (AmiA, AmiB and AmiC) required for Escherichia coli cell division. Poorly regulated amiB mutants were isolated encoding lytic AmiB variants with elevated basal PG hydrolase activities in vitro. The structure of an AmiB orthologue was also solved, revealing that the active site of AmiB is occluded by a conserved alpha helix. Strikingly, most of the amino acid substitutions in the lytic AmiB variants mapped to this domain and are predicted to disrupt its interaction with the active site. Our results therefore support a model in which cell separation is stimulated by the reversible relief of amidase autoinhibition governed by conserved subcomplexes within the cytokinetic ring. Analogous conformational control mechanisms are likely to be part of a general strategy used to control PG hydrolases present within multienzyme PG-remodelling machines.

  14. Controlling conformational flexibility of an O₂-binding H-NOX domain.

    PubMed

    Weinert, Emily E; Phillips-Piro, Christine M; Tran, Rosalie; Mathies, Richard A; Marletta, Michael A

    2011-08-16

    Heme Nitric oxide/OXygen binding (H-NOX) domains have provided a novel scaffold to probe ligand affinity in hemoproteins. Mutation of isoleucine 5, a conserved residue located in the heme-binding pocket of the H-NOX domain from Thermoanaerobacter tengcongensis (Tt H-NOX), was carried out to examine changes in oxygen (O(2))-binding properties. A series of I5 mutants (I5F, I5F/I75F, I5F/L144F, I5F/I75F/L144F) were investigated to probe the role of steric bulk within the heme pocket. The mutations significantly increased O(2) association rates (1.5-2.5-fold) and dissociation rates (8-190-fold) as compared to wild-type Tt H-NOX. Structural changes that accompanied the I5F mutation were characterized using X-ray crystallography and resonance Raman spectroscopy. A 1.67 Å crystal structure of the I5F mutant indicated that introducing a phenylalanine at position 5 resulted in a significant shift of the N-terminal domain of the protein, causing an opening of the heme pocket. This movement also resulted in an increased amount of flexibility at the N-terminus and the loop covering the N-terminal helix as indicated by the two conformations of the first six N-terminal amino acids, high B-factors in this region of the protein, and partially discontinuous electron density. In addition, introduction of a phenylalanine at position 5 resulted in increased flexibility of the heme within the pocket and weakened hydrogen bonding to the bound O(2) as measured by resonance Raman spectroscopy. This study provides insight into the critical role of I5 in controlling conformational flexibility and ligand affinity in H-NOX proteins.

  15. PH Sensitive Polymers for Improving Reservoir Sweep and Conformance Control in Chemical Flooring

    SciTech Connect

    Mukul Sharma; Steven Bryant; Chun Huh

    2008-03-31

    There is an increasing opportunity to recover bypassed oil from depleted, mature oilfields in the US. The recovery factor in many reservoirs is low due to inefficient displacement of the oil by injected fluids (typically water). The use of chemical flooding methods to increase recovery efficiencies is severely constrained by the inability of the injected chemicals to contact the bypassed oil. Low sweep efficiencies are the primary cause of low oil recoveries observed in the field in chemical flooding operations even when lab studies indicate high oil recovery efficiency. Any technology that increases the ability of chemical flooding agents to better contact the remaining oil and reduce the amount of water produced in conjunction with the produced oil will have a significant impact on the cost of producing oil domestically in the US. This translates directly into additional economically recoverable reserves, which extends the economic lives of marginal and mature wells. The objective of this research project was to develop a low-cost, pH-triggered polymer for use in IOR processes to improve reservoir sweep efficiency and reservoir conformance in chemical flooding. Rheological measurements made on the polymer solution, clearly show that it has a low viscosity at low pH and exhibits a sudden increase in viscosity (by 2 orders of magnitude or more) at a pH of 3.5 to 4. This implies that the polymer would preferentially flow into zones containing water since the effective permeability to water is highest in these zones. As the pH of the zone increases due to the buffering capacity of the reservoir rock, the polymer solution undergoes a liquid to gel transition causing a sharp increase in the viscosity of the polymer solution in these zones. This allows operationally robust, in-depth conformance treatment of such water bearing zones and better mobility control. The rheological properties of HPAM solutions were measured. These include: steady-shear viscosity and

  16. Synthesis and NMR Analysis of a Conformationally Controlled β-Turn Mimetic Torsion Balance.

    PubMed

    Lypson, Alyssa B; Wilcox, Craig S

    2017-01-20

    The molecular torsion balance concept was applied to a new conformationally controlled scaffold and synthesized to accurately evaluate pairwise amino acid interactions in an antiparallel β-sheet motif. The scaffold's core design combines (ortho-tolyl)amide and o,o,o'-trisubstituted biphenyl structural units to provide a geometry better-suited for intramolecular hydrogen bonding. Like the dibenzodiazocine hinge of the traditional torsion balance, the (ortho-tolyl)amide unit offers restricted rotation around an N-aryl bond. The resulting two-state folding model is a powerful template for measuring hydrogen bond stability between two competing sequences. The aim of this study was to improve the alignment between the amino acid sequences attached to the upper and lower aromatic rings in order to promote hydrogen bond formation at the correct distance and antiparallel orientation. Bromine substituents were introduced ortho to the upper side chains and compared to a control to test our hypothesis. Hydrogen bond formation has been identified between the NH amide proton of the upper side chain (proton donor) and glycine acetamide of the lower side chain (proton acceptor).

  17. KTN (RCK) Domains Regulate K+ Channels and Transporters by Controlling the Dimer-Hinge Conformation

    PubMed Central

    Roosild, Tarmo P.; Castronovo, Samantha; Miller, Samantha; Li, Chan; Rasmussen, Tim; Bartlett, Wendy; Gunasekera, Banuri; Choe, Senyon; Booth, Ian R.

    2009-01-01

    Summary KTN (RCK) domains are nucleotide-binding folds that form the cytoplasmic regulatory complexes of various K+ channels and transporters. The mechanisms these proteins use to control their transmembrane pore-forming counterparts remains unclear despite numerous electrophysiological and structural studies. KTN (RCK) domains consistently crystallize as dimers within the asymmetric unit, forming a pronounced hinge between two Rossmann folds. We have previously proposed that modification of the hinge angle plays an important role in activating the associated membrane-integrated components of the channel or transporter. Here we report the structure of the C-terminal, KTN-bearing domain of the E. coli KefC K+ efflux system in association with the ancillary subunit, KefF, which is known to stabilize the conductive state. The structure of the complex and functional analysis of KefC variants reveal that control of the conformational flexibility inherent in the KTN dimer hinge is modulated by KefF and essential for regulation of KefC ion flux. PMID:19523906

  18. Chemical design enables the control of conformational polymorphism in functional 2,3-thieno(bis)imide-ended materials.

    PubMed

    Maini, Lucia; Gallino, Federico; Zambianchi, Massimo; Durso, Margherita; Gazzano, Massimo; Rubini, Katia; Gentili, Denis; Manet, Ilse; Muccini, Michele; Toffanin, Stefano; Cavallini, Massimiliano; Melucci, Manuela

    2015-02-07

    We report a successful chemical design strategy based on the even-odd alkyl end tailoring, which allows us to promote and control conformational polymorphism in single crystal and thin deposits of thienoimide-based molecular semiconductors (Cx-NT4N).

  19. Dynamic organization of the mitochondrial protein import machinery.

    PubMed

    Straub, Sebastian P; Stiller, Sebastian B; Wiedemann, Nils; Pfanner, Nikolaus

    2016-11-01

    Mitochondria contain elaborate machineries for the import of precursor proteins from the cytosol. The translocase of the outer mitochondrial membrane (TOM) performs the initial import of precursor proteins and transfers the precursors to downstream translocases, including the presequence translocase and the carrier translocase of the inner membrane, the mitochondrial import and assembly machinery of the intermembrane space, and the sorting and assembly machinery of the outer membrane. Although the protein translocases can function as separate entities in vitro, recent studies revealed a close and dynamic cooperation of the protein import machineries to facilitate efficient transfer of precursor proteins in vivo. In addition, protein translocases were found to transiently interact with distinct machineries that function in the respiratory chain or in the maintenance of mitochondrial membrane architecture. Mitochondrial protein import is embedded in a regulatory network that ensures protein biogenesis, membrane dynamics, bioenergetic activity and quality control.

  20. MACHINERY RESONANCE AND DRILLING

    SciTech Connect

    Leishear, R.; Fowley, M.

    2010-01-23

    New developments in vibration analysis better explain machinery resonance, through an example of drill bit chattering during machining of rusted steel. The vibration of an operating drill motor was measured, the natural frequency of an attached spring was measured, and the two frequencies were compared to show that the system was resonant. For resonance to occur, one of the natural frequencies of a structural component must be excited by a cyclic force of the same frequency. In this case, the frequency of drill bit chattering due to motor rotation equaled the spring frequency (cycles per second), and the system was unstable. A soft rust coating on the steel to be drilled permitted chattering to start at the drill bit tip, and the bit oscillated on and off of the surface, which increased the wear rate of the drill bit. This resonant condition is typically referred to as a motor critical speed. The analysis presented here quantifies the vibration associated with this particular critical speed problem, using novel techniques to describe resonance.

  1. Direct electrical control of IgG conformation and functional activity at surfaces

    NASA Astrophysics Data System (ADS)

    Ghisellini, Paola; Caiazzo, Marialuisa; Alessandrini, Andrea; Eggenhöffner, Roberto; Vassalli, Massimo; Facci, Paolo

    2016-11-01

    We have devised a supramolecular edifice involving His-tagged protein A and antibodies to yield surface immobilized, uniformly oriented, IgG-type, antibody layers with Fab fragments exposed off an electrode surface. We demonstrate here that we can affect the conformation of IgGs, likely pushing/pulling electrostatically Fab fragments towards/from the electrode surface. A potential difference between electrode and solution acts on IgGs’ charged aminoacids modulating the accessibility of the specific recognition regions of Fab fragments by antigens in solution. Consequently, antibody-antigen affinity is affected by the sign of the applied potential: a positive potential enables an effective capture of antigens; a negative one pulls the fragments towards the electrode, where steric hindrance caused by neighboring molecules largely hampers the capture of antigens. Different experimental techniques (electrochemical quartz crystal microbalance, electrochemical impedance spectroscopy, fluorescence confocal microscopy and electrochemical atomic force spectroscopy) were used to evaluate binding kinetics, surface coverage, effect of the applied electric field on IgGs, and role of charged residues on the phenomenon described. These findings expand the concept of electrical control of biological reactions and can be used to gate electrically specific recognition reactions with impact in biosensors, bioactuators, smart biodevices, nanomedicine, and fundamental studies related to chemical reaction kinetics.

  2. Area-Selective Atomic Layer Deposition: Conformal Coating, Subnanometer Thickness Control, and Smart Positioning.

    PubMed

    Fang, Ming; Ho, Johnny C

    2015-09-22

    Transistors have already been made three-dimensional (3D), with device channels (i.e., fins in trigate field-effect transistor (FinFET) technology) that are taller, thinner, and closer together in order to enhance device performance and lower active power consumption. As device scaling continues, these transistors will require more advanced, fabrication-enabling technologies for the conformal deposition of high-κ dielectric layers on their 3D channels with accurate position alignment and thickness control down to the subnanometer scale. Among many competing techniques, area-selective atomic layer deposition (AS-ALD) is a promising method that is well suited to the requirements without the use of complicated, complementary metal-oxide semiconductor (CMOS)-incompatible processes. However, further progress is limited by poor area selectivity for thicker films formed via a higher number of ALD cycles as well as the prolonged processing time. In this issue of ACS Nano, Professor Stacy Bent and her research group demonstrate a straightforward self-correcting ALD approach, combining selective deposition with a postprocess mild chemical etching, which enables selective deposition of dielectric films with thicknesses and processing times at least 10 times larger and 48 times shorter, respectively, than those obtained by conventional AS-ALD processes. These advances present an important technological breakthrough that may drive the AS-ALD technique a step closer toward industrial applications in electronics, catalysis, and photonics, etc. where more efficient device fabrication processes are needed.

  3. Direct electrical control of IgG conformation and functional activity at surfaces

    PubMed Central

    Ghisellini, Paola; Caiazzo, Marialuisa; Alessandrini, Andrea; Eggenhöffner, Roberto; Vassalli, Massimo; Facci, Paolo

    2016-01-01

    We have devised a supramolecular edifice involving His-tagged protein A and antibodies to yield surface immobilized, uniformly oriented, IgG-type, antibody layers with Fab fragments exposed off an electrode surface. We demonstrate here that we can affect the conformation of IgGs, likely pushing/pulling electrostatically Fab fragments towards/from the electrode surface. A potential difference between electrode and solution acts on IgGs’ charged aminoacids modulating the accessibility of the specific recognition regions of Fab fragments by antigens in solution. Consequently, antibody-antigen affinity is affected by the sign of the applied potential: a positive potential enables an effective capture of antigens; a negative one pulls the fragments towards the electrode, where steric hindrance caused by neighboring molecules largely hampers the capture of antigens. Different experimental techniques (electrochemical quartz crystal microbalance, electrochemical impedance spectroscopy, fluorescence confocal microscopy and electrochemical atomic force spectroscopy) were used to evaluate binding kinetics, surface coverage, effect of the applied electric field on IgGs, and role of charged residues on the phenomenon described. These findings expand the concept of electrical control of biological reactions and can be used to gate electrically specific recognition reactions with impact in biosensors, bioactuators, smart biodevices, nanomedicine, and fundamental studies related to chemical reaction kinetics. PMID:27883075

  4. Disease Control After Reduced Volume Conformal and Intensity Modulated Radiation Therapy for Childhood Craniopharyngioma

    SciTech Connect

    Merchant, Thomas E.; Kun, Larry E.; Hua, Chia-Ho; Wu, Shengjie; Xiong, Xiaoping; Sanford, Robert A.; Boop, Frederick A.

    2013-03-15

    Purpose: To estimate the rate of disease control after conformal radiation therapy using reduced clinical target volume (CTV) margins and to determine factors that predict for tumor progression. Methods and Materials: Eighty-eight children (median age, 8.5 years; range, 3.2-17.6 years) received conformal or intensity modulated radiation therapy between 1998 and 2009. The study group included those prospectively treated from 1998 to 2003, using a 10-mm CTV, defined as the margin surrounding the solid and cystic tumor targeted to receive the prescription dose of 54 Gy. The CTV margin was subsequently reduced after 2003, yielding 2 groups of patients: those treated with a CTV margin greater than 5 mm (n=26) and those treated with a CTV margin less than or equal to 5 mm (n=62). Disease progression was estimated on the basis of additional variables including sex, race, extent of resection, tumor interventions, target volume margins, and frequency of weekly surveillance magnetic resonance (MR) imaging during radiation therapy. Median follow-up was 5 years. Results: There was no difference between progression-free survival rates based on CTV margins (>5 mm vs ≤5 mm) at 5 years (88.1% ± 6.3% vs 96.2% ± 4.4% [P=.6386]). There were no differences based on planning target volume (PTV) margins (or combined CTV plus PTV margins). The PTV was systematically reduced from 5 to 3 mm during the time period of the study. Factors predictive of superior progression-free survival included Caucasian race (P=.0175), no requirement for cerebrospinal fluid shunting (P=.0066), and number of surveillance imaging studies during treatment (P=.0216). Patients whose treatment protocol included a higher number of weekly surveillance MR imaging evaluations had a lower rate of tumor progression. Conclusions: These results suggest that targeted volume reductions for radiation therapy using smaller margins are feasible and safe but require careful monitoring. We are currently investigating

  5. Surface control of alkyl chain conformations and 2D chiral amplification.

    PubMed

    Hauptmann, Nadine; Scheil, Katharina; Gopakumar, Thiruvancheril G; Otte, Franziska L; Schütt, Christian; Herges, Rainer; Berndt, Richard

    2013-06-19

    Trioctyl-functionalized triazatriangulenium (trioctyl-TATA) deposited on Au(111) and Ag(111) surfaces by electrospray ionization was investigated using low-temperature scanning tunneling microscopy. The molecule surprisingly adsorbs with gauche rather than anti conformations of the octyl groups. We observed chiral amplification in the islands. Only one of the eight possible configurations of the octyl groups was found in homochiral hexagonal networks. Quantum-chemical calculations confirmed and explained the preference for the gauche conformations of adsorbed trioctyl-TATA.

  6. Conformational control in a bipyridine linked π-conjugated oligomer: cation mediated helix unfolding and refolding.

    PubMed

    Divya, Kizhumuri P; Sreejith, Sivaramapanicker; Suresh, Cherumuttathu H; Ajayaghosh, Ayyappanpillai

    2010-11-28

    A chiral π-conjugated oligomer having alternate bipyridine and carbazole moieties connected through acetylinic bonds undergoes helical folding in chloroform-acetonitrile (40/60, v/v) as evident by fluorescence and circular dichroism changes. In the presence of transition metal cations such as Zn(2+) defolding of the helical conformation occurs. Upon decomplexation of the cation with EDTA, the helical conformation is regained.

  7. A perspective on conformational control of electron transfer in nitric oxide synthases.

    PubMed

    Hedison, Tobias M; Hay, Sam; Scrutton, Nigel S

    2017-02-28

    This perspective reviews single molecule and ensemble fluorescence spectroscopy studies of the three tissue specific nitric oxide synthase (NOS) isoenzymes and the related diflavin oxidoreductase cytochrome P450 reductase. The focus is on the role of protein dynamics and the protein conformational landscape and we discuss how recent fluorescence-based studies have helped in illustrating how the nature of the NOS conformational landscape relates to enzyme turnover and catalysis.

  8. Controlling Protein Conformations to Explore Unprecedented Material Properties by Single-Molecule Surgery

    DTIC Science & Technology

    2012-08-17

    Molecule Protein Conformational Dynamics in Enzymatic Reactions,” Single-Molecule Biophysics Meeting, Aspen , CO, Jan. 4-10, 2009. H. P. Lu, “Single...Donor-Acceptor: Cy3-Cy5) pair labeled HPPK molecule tethered between a glass cover-slip surface and a handle (biotin group plus streptavidin), and a...5, 2008. H. P. Lu, “Probing Single-Molecule Protein Conformational Dynamics in Enzymatic Reactions,” Single-Molecule Biophysics Meeting, Aspen

  9. Two Na+ Sites Control Conformational Change in a Neurotransmitter Transporter Homolog*

    PubMed Central

    Tavoulari, Sotiria; Margheritis, Eleonora; Nagarajan, Anu; DeWitt, David C.; Zhang, Yuan-Wei; Rosado, Edwin; Ravera, Silvia; Rhoades, Elizabeth; Forrest, Lucy R.; Rudnick, Gary

    2016-01-01

    In LeuT, a prokaryotic homolog of neurotransmitter transporters, Na+ stabilizes outward-open conformational states. We examined how each of the two LeuT Na+ binding sites contributes to Na+-dependent closure of the cytoplasmic pathway using biochemical and biophysical assays of conformation. Mutating either of two residues that contribute to the Na2 site completely prevented cytoplasmic closure in response to Na+, suggesting that Na2 is essential for this conformational change, whereas Na1 mutants retained Na+ responsiveness. However, mutation of Na1 residues also influenced the Na+-dependent conformational change in ways that varied depending on the position mutated. Computational analyses suggest those mutants influence the ability of Na1 binding to hydrate the substrate pathway and perturb an interaction network leading to the extracellular gate. Overall, the results demonstrate that occupation of Na2 stabilizes outward-facing conformations presumably through a direct interaction between Na+ and transmembrane helices 1 and 8, whereas Na+ binding at Na1 influences conformational change through a network of intermediary interactions. The results also provide evidence that N-terminal release and helix motions represent distinct steps in cytoplasmic pathway opening. PMID:26582198

  10. Two Na+ Sites Control Conformational Change in a Neurotransmitter Transporter Homolog.

    PubMed

    Tavoulari, Sotiria; Margheritis, Eleonora; Nagarajan, Anu; DeWitt, David C; Zhang, Yuan-Wei; Rosado, Edwin; Ravera, Silvia; Rhoades, Elizabeth; Forrest, Lucy R; Rudnick, Gary

    2016-01-15

    In LeuT, a prokaryotic homolog of neurotransmitter transporters, Na(+) stabilizes outward-open conformational states. We examined how each of the two LeuT Na(+) binding sites contributes to Na(+)-dependent closure of the cytoplasmic pathway using biochemical and biophysical assays of conformation. Mutating either of two residues that contribute to the Na2 site completely prevented cytoplasmic closure in response to Na(+), suggesting that Na2 is essential for this conformational change, whereas Na1 mutants retained Na(+) responsiveness. However, mutation of Na1 residues also influenced the Na(+)-dependent conformational change in ways that varied depending on the position mutated. Computational analyses suggest those mutants influence the ability of Na1 binding to hydrate the substrate pathway and perturb an interaction network leading to the extracellular gate. Overall, the results demonstrate that occupation of Na2 stabilizes outward-facing conformations presumably through a direct interaction between Na(+) and transmembrane helices 1 and 8, whereas Na(+) binding at Na1 influences conformational change through a network of intermediary interactions. The results also provide evidence that N-terminal release and helix motions represent distinct steps in cytoplasmic pathway opening.

  11. Palmitoylation regulates glutamate receptor distributions in postsynaptic densities through control of PSD95 conformation and orientation

    PubMed Central

    Jeyifous, Okunola; Lin, Eric I.; Chen, Xiaobing; Antinone, Sarah E.; Mastro, Ryan; Drisdel, Renaldo; Reese, Thomas S.; Green, William N.

    2016-01-01

    Postsynaptic density protein 95 (PSD95) and synapse-associated protein 97 (SAP97) are homologous scaffold proteins with different N-terminal domains, possessing either a palmitoylation site (PSD95) or an L27 domain (SAP97). Here, we measured PSD95 and SAP97 conformation in vitro and in postsynaptic densities (PSDs) using FRET and EM, and examined how conformation regulated interactions with AMPA-type and NMDA-type glutamate receptors (AMPARs/NMDARs). Palmitoylation of PSD95 changed its conformation from a compact to an extended configuration. PSD95 associated with AMPARs (via transmembrane AMPAR regulatory protein subunits) or NMDARs [via glutamate ionotropic receptor NMDA-type subunit 2B (GluN2B) subunits] only in its palmitoylated and extended conformation. In contrast, in its extended conformation, SAP97 associates with NMDARs, but not with AMPARs. Within PSDs, PSD95 and SAP97 were largely in the extended conformation, but had different orientations. PSD95 oriented perpendicular to the PSD membrane, with its palmitoylated, N-terminal domain at the membrane. SAP97 oriented parallel to the PSD membrane, likely as a dimer through interactions of its N-terminal L27 domain. Changing PSD95 palmitoylation in PSDs altered PSD95 and AMPAR levels but did not affect NMDAR levels. These results indicate that in PSDs, PSD95 palmitoylation, conformation, and its interactions are dynamic when associated with AMPARs and more stable when associated with NMDARs. Altogether, our results are consistent with differential regulation of PSD95 palmitoylation in PSDs resulting from the clustering of palmitoylating and depalmitoylating enzymes into AMPAR nanodomains segregated away from NMDAR nanodomains. PMID:27956638

  12. An RNAi-Based Control of Fusarium graminearum Infections Through Spraying of Long dsRNAs Involves a Plant Passage and Is Controlled by the Fungal Silencing Machinery.

    PubMed

    Koch, Aline; Biedenkopf, Dagmar; Furch, Alexandra; Weber, Lennart; Rossbach, Oliver; Abdellatef, Eltayb; Linicus, Lukas; Johannsmeier, Jan; Jelonek, Lukas; Goesmann, Alexander; Cardoza, Vinitha; McMillan, John; Mentzel, Tobias; Kogel, Karl-Heinz

    2016-10-01

    Meeting the increasing food and energy demands of a growing population will require the development of ground-breaking strategies that promote sustainable plant production. Host-induced gene silencing has shown great potential for controlling pest and diseases in crop plants. However, while delivery of inhibitory noncoding double-stranded (ds)RNA by transgenic expression is a promising concept, it requires the generation of transgenic crop plants which may cause substantial delay for application strategies depending on the transformability and genetic stability of the crop plant species. Using the agronomically important barley-Fusarium graminearum pathosystem, we alternatively demonstrate that a spray application of a long noncoding dsRNA (791 nt CYP3-dsRNA), which targets the three fungal cytochrome P450 lanosterol C-14α-demethylases, required for biosynthesis of fungal ergosterol, inhibits fungal growth in the directly sprayed (local) as well as the non-sprayed (distal) parts of detached leaves. Unexpectedly, efficient spray-induced control of fungal infections in the distal tissue involved passage of CYP3-dsRNA via the plant vascular system and processing into small interfering (si)RNAs by fungal DICER-LIKE 1 (FgDCL-1) after uptake by the pathogen. We discuss important consequences of this new finding on future RNA-based disease control strategies. Given the ease of design, high specificity, and applicability to diverse pathogens, the use of target-specific dsRNA as an anti-fungal agent offers unprecedented potential as a new plant protection strategy.

  13. An RNAi-Based Control of Fusarium graminearum Infections Through Spraying of Long dsRNAs Involves a Plant Passage and Is Controlled by the Fungal Silencing Machinery

    PubMed Central

    Koch, Aline; Furch, Alexandra; Weber, Lennart; Rossbach, Oliver; Abdellatef, Eltayb; Linicus, Lukas; Jelonek, Lukas; Goesmann, Alexander; Cardoza, Vinitha; McMillan, John; Mentzel, Tobias; Kogel, Karl-Heinz

    2016-01-01

    Meeting the increasing food and energy demands of a growing population will require the development of ground-breaking strategies that promote sustainable plant production. Host-induced gene silencing has shown great potential for controlling pest and diseases in crop plants. However, while delivery of inhibitory noncoding double-stranded (ds)RNA by transgenic expression is a promising concept, it requires the generation of transgenic crop plants which may cause substantial delay for application strategies depending on the transformability and genetic stability of the crop plant species. Using the agronomically important barley—Fusarium graminearum pathosystem, we alternatively demonstrate that a spray application of a long noncoding dsRNA (791 nt CYP3-dsRNA), which targets the three fungal cytochrome P450 lanosterol C-14α-demethylases, required for biosynthesis of fungal ergosterol, inhibits fungal growth in the directly sprayed (local) as well as the non-sprayed (distal) parts of detached leaves. Unexpectedly, efficient spray-induced control of fungal infections in the distal tissue involved passage of CYP3-dsRNA via the plant vascular system and processing into small interfering (si)RNAs by fungal DICER-LIKE 1 (FgDCL-1) after uptake by the pathogen. We discuss important consequences of this new finding on future RNA-based disease control strategies. Given the ease of design, high specificity, and applicability to diverse pathogens, the use of target-specific dsRNA as an anti-fungal agent offers unprecedented potential as a new plant protection strategy. PMID:27737019

  14. Dynamic control of protein conformation transition in chromatographic separation based on hydrophobic interactions: molecular dynamics simulation.

    PubMed

    Zhang, Lin; Lu, Diannan; Liu, Zheng

    2009-03-20

    Conformational transitions of a protein in hydrophobic interaction based chromatography, including hydrophobic interaction chromatography (HIC) and reversed-phase liquid chromatography (RPLC), and their impact on the separation process and performance were probed by molecular dynamics simulation of a 46-bead beta-barrel coarse-grained model protein in a confined pore, which represents the porous adsorbent. The transition of the adsorbed protein from the native conformation to an unfolded one occurred as a result of strong hydrophobic interactions with the pore surface, which reduced the formation of protein aggregates. The conformational transition was also displayed in the simulation once an elution buffer characterized by weaker hydrophobicity was introduced to strip protein from pore surface. The discharged proteins that underwent conformational transition were prone to aggregation; thus, an unsatisfactory yield of the native protein was obtained. An orthogonal experiment revealed that in addition to the strengths of the protein-protein and protein-adsorbent hydrophobic interactions, the elution time required to reduce the above-mentioned interactions also determined the yield of native protein by HIC and RPLC. Stepwise elution, characterized by sequential reduction of the hydrophobic interactions between the protein and adsorbent, was presented as a dynamic strategy for tuning conformational transitions to favor the native conformation and reduce the formation of protein aggregates during the elution process. The yield of the native protein obtained by this dynamic operation strategy was higher than that obtained by steady-state elution. The simulation study qualitatively reproduced the experimental observations and provided molecular insight that would be helpful for designing and optimizing HIC and RPLC separation of proteins.

  15. Conformation-selective ATP-competitive inhibitors control regulatory interactions and noncatalytic functions of mitogen-activated protein kinases.

    PubMed

    Hari, Sanjay B; Merritt, Ethan A; Maly, Dustin J

    2014-05-22

    Most potent protein kinase inhibitors act by competing with ATP to block the phosphotransferase activity of their targets. However, emerging evidence demonstrates that ATP-competitive inhibitors can affect kinase interactions and functions in ways beyond blocking catalytic activity. Here, we show that stabilizing alternative ATP-binding site conformations of the mitogen-activated protein kinases (MAPKs) p38α and Erk2 with ATP-competitive inhibitors differentially, and in some cases divergently, modulates the abilities of these kinases to interact with upstream activators and deactivating phosphatases. Conformation-selective ligands are also able to modulate Erk2's ability to allosterically activate the MAPK phosphatase DUSP6, highlighting how ATP-competitive ligands can control noncatalytic kinase functions. Overall, these studies underscore the relationship between the ATP-binding and regulatory sites of MAPKs and provide insight into how ATP-competitive ligands can be designed to confer graded control over protein kinase function.

  16. COMBINED MICROBIAL SURFACTANT-POLYMER SYSTEM FOR IMPROVED OIL MOBILITY AND CONFORMANCE CONTROL

    SciTech Connect

    Jorge Gabitto; Maria Barrufet

    2005-08-01

    show a significant influence of nutrient regime on alternate production of surfactants or polymers for a Bacillus licheniformis strain, NIPER 1A. The main conclusion of this work is that NIPER 1A can produce both surfactant and polymer by nutrient regime manipulation. Our experiments proved that this property leads to improved oil recovery by increasing alternatively, oil mobility and conformance control.

  17. Use of 1–4 interaction scaling factors to control the conformational equilibrium between α-helix and β-strand

    SciTech Connect

    Pang, Yuan-Ping

    2015-02-06

    Highlights: • 1–4 interaction scaling factors are used to adjust conformational energy. • This article reports the effects of these factors on protein conformations. • Reducing these factors changes a helix to a strand in molecular dynamics simulation. • Increasing these factors causes the reverse conformational change. • These factors control the conformational equilibrium between helix and strand. - Abstract: 1–4 interaction scaling factors are used in AMBER forcefields to reduce the exaggeration of short-range repulsion caused by the 6–12 Lennard-Jones potential and a nonpolarizable charge model and to obtain better agreements of small-molecule conformational energies with experimental data. However, the effects of these scaling factors on protein secondary structure conformations have not been investigated until now. This article reports the finding that the 1–4 interactions among the protein backbone atoms separated by three consecutive covalent bonds are more repulsive in the α-helix conformation than in two β-strand conformations. Therefore, the 1–4 interaction scaling factors of protein backbone torsions ϕ and ψ control the conformational equilibrium between α-helix and β-strand. Molecular dynamics simulations confirm that reducing the ϕ and ψ scaling factors readily converts the α-helix conformation of AcO-(AAQAA){sub 3}-NH{sub 2} to a β-strand conformation, and the reverse occurs when these scaling factors are increased. These results suggest that the ϕ and ψ scaling factors can be used to generate the α-helix or β-strand conformation in situ and to control the propensities of a forcefield for adopting secondary structure elements.

  18. GPCR signalling to the translation machinery.

    PubMed

    Musnier, Astrid; Blanchot, Benoît; Reiter, Eric; Crépieux, Pascale

    2010-05-01

    G protein-coupled receptors (GPCRs) are involved in most physiological processes, many of them being engaged in fully differentiated cells. These receptors couple to transducers of their own, primarily G proteins and beta-arrestins, which launch intracellular signalling cascades. Some of these signalling events regulate the translational machinery to fine-tune general cell metabolism or to alter protein expression pattern. Though extensively documented for tyrosine kinase receptors, translational regulation by GPCRs is still poorly appreciated. The objective of this review paper is to address the following questions: i) is there a "GPCR signature" impacting on the translational machinery, and ultimately on the type of mRNA translated? ii) are the regulatory networks involved similar as those utilized by tyrosine kinase receptors? In particular, we will discuss the specific features of translational control mediated by GPCRs and highlight the intrinsic properties of GPCRs these mechanisms could rely on.

  19. PERSPECTIVE: Intra-molecular chaperone: the role of the N-terminal in conformational selection and kinetic control

    NASA Astrophysics Data System (ADS)

    Tsai, Chung-Jung; Ma, Buyong; Nussinov, Ruth

    2009-03-01

    The vast majority of the proteins in nature are under thermodynamic control, consistent with the universally accepted notion that proteins exist in their thermodynamically most stable state. Yet, recently a number of examples of proteins whose fold is under kinetic control have come to light. Their functions and environments vary. The first among these are some proteases, discovered in the early 1990s. There, an N-terminal proregion is self-cleaved after the protein folded, leaving the remainder of the chain in a kinetically trapped state. A related scenario was observed for microcin J25, an antibacterial peptide. This peptide presents a trapped covalently knotted conformation. The third and the most recently discovered case is the multidrug-resistant transporter protein, P-glycoprotein. There, a synonymous 'silent' mutation leads to ribosome stalling with a consequent altered kinetically trapped state. Here we argue that in all three examples, the N-terminal plays the role of an intra-molecular chaperone, that is, the N-terminal conformation selects among all competing local conformations of a downstream segment. By providing a pattern, the N-terminal chaperone segment assists the protein folding process. If the N-terminal is subsequently cleaved, the protein can be under kinetic control, since it is trapped in a thermodynamically less-stable state.

  20. Control of Reaction Surface in Low Temperature CVD to Enhance Nucleation and Conformal Coverage

    ERIC Educational Resources Information Center

    Kumar, Navneet

    2009-01-01

    The Holy Grail in CVD community is to find precursors that can afford the following: good nucleation on a desired substrate and conformal deposition in high AR features. Good nucleation is not only necessary for getting ultra-thin films at low thicknesses; it also offers films that are smooth at higher thickness values. On the other hand,…

  1. Control of Reaction Surface in Low Temperature CVD to Enhance Nucleation and Conformal Coverage

    ERIC Educational Resources Information Center

    Kumar, Navneet

    2009-01-01

    The Holy Grail in CVD community is to find precursors that can afford the following: good nucleation on a desired substrate and conformal deposition in high AR features. Good nucleation is not only necessary for getting ultra-thin films at low thicknesses; it also offers films that are smooth at higher thickness values. On the other hand,…

  2. The first case of actinide triple helices: pH-dependent structural evolution and kinetically-controlled transformation of two supramolecular conformational isomers.

    PubMed

    An, Shu-wen; Mei, Lei; Wang, Cong-zhi; Xia, Chuan-qin; Chai, Zhi-fang; Shi, Wei-qun

    2015-05-28

    The first actinide triple helices, including two supramolecular conformational isomers of uranium(VI), have been synthesized with the aid of a flexible V-shaped ligand and a rigid aromatic base. The isomers exhibit an intriguing pH-dependent structural evolution and a kinetically-controlled transformation via a novel conformational rearrangement of the organic base.

  3. Control of stem cell self-renewal and differentiation by the heterochronic genes and the cellular asymmetry machinery in Caenorhabditis elegans

    PubMed Central

    Harandi, Omid F.; Ambros, Victor R.

    2015-01-01

    Transitions between asymmetric (self-renewing) and symmetric (proliferative) cell divisions are robustly regulated in the context of normal development and tissue homeostasis. To genetically assess the regulation of these transitions, we used the postembryonic epithelial stem (seam) cell lineages of Caenorhabditis elegans. In these lineages, the timing of these transitions is regulated by the evolutionarily conserved heterochronic pathway, whereas cell division asymmetry is conferred by a pathway consisting of Wnt (Wingless) pathway components, including posterior pharynx defect (POP-1)/TCF, APC related/adenomatosis polyposis coli (APR-1)/APC, and LIT-1/NLK (loss of intestine/Nemo-like kinase). Here we explore the genetic regulatory mechanisms underlying stage-specific transitions between self-renewing and proliferative behavior in the seam cell lineages. We show that mutations of genes in the heterochronic developmental timing pathway, including lin-14 (lineage defect), lin-28, lin-46, and the lin-4 and let-7 (lethal defects)-family microRNAs, affect the activity of LIT-1/POP-1 cellular asymmetry machinery and APR-1 polarity during larval development. Surprisingly, heterochronic mutations that enhance LIT-1 activity in seam cells can simultaneously also enhance the opposing, POP-1 activity, suggesting a role in modulating the potency of the cellular polarizing activity of the LIT-1/POP-1 system as development proceeds. These findings illuminate how the evolutionarily conserved cellular asymmetry machinery can be coupled to microRNA-regulated developmental pathways for robust regulation of stem cell maintenance and proliferation during the course of development. Such genetic interactions between developmental timing regulators and cell polarity regulators could underlie transitions between asymmetric and symmetric stem cell fates in other systems and could be deregulated in the context of developmental disorders and cancer. PMID:25561544

  4. Impact of microscopic disease extension, extra-CTV tumour islets, incidental dose and dose conformity on tumour control probability.

    PubMed

    Selvaraj, Jothybasu; Baker, Colin; Nahum, Alan

    2016-06-01

    The impact of microscopic disease extension (MDE), extra-CTV tumour islets (TIs), incidental dose and dose conformity on tumour control probability (TCP) is analyzed using insilico simulations in this study. MDE in the region in between GTV and CTV is simulated inclusive of geometric uncertainties (GE) using spherical targets and spherical dose distribution. To study the effect of incidental dose on TIs and the effect of dose-response curve (DRC) on tumour control, islets were randomly distributed and TCP was calculated for various dose levels by rescaling the dose. Further, the impact of dose conformity on required PTV margins is also studied. The required PTV margins are ~2 mm lesser than assuming a uniform clonogen density if an exponential clonogen density fall off in the GTV-CTV is assumed. However, margins are almost equal if GE is higher in both cases. This shows that GE has a profound impact on margins. The effect of TIs showed a bi-phasic relation with increasing dose, indicating that patients with islets not in the beam paths do not benefit from dose escalation. Increasing dose conformity is also found to have considerable effect on TCP loss especially for larger GE. Further, smaller margins in IGRT should be used with caution where uncertainty in CTV definition is of concern.

  5. Conformal Nets II: Conformal Blocks

    NASA Astrophysics Data System (ADS)

    Bartels, Arthur; Douglas, Christopher L.; Henriques, André

    2017-08-01

    Conformal nets provide a mathematical formalism for conformal field theory. Associated to a conformal net with finite index, we give a construction of the `bundle of conformal blocks', a representation of the mapping class groupoid of closed topological surfaces into the category of finite-dimensional projective Hilbert spaces. We also construct infinite-dimensional spaces of conformal blocks for topological surfaces with smooth boundary. We prove that the conformal blocks satisfy a factorization formula for gluing surfaces along circles, and an analogous formula for gluing surfaces along intervals. We use this interval factorization property to give a new proof of the modularity of the category of representations of a conformal net.

  6. Conformal Nets II: Conformal Blocks

    NASA Astrophysics Data System (ADS)

    Bartels, Arthur; Douglas, Christopher L.; Henriques, André

    2017-03-01

    Conformal nets provide a mathematical formalism for conformal field theory. Associated to a conformal net with finite index, we give a construction of the `bundle of conformal blocks', a representation of the mapping class groupoid of closed topological surfaces into the category of finite-dimensional projective Hilbert spaces. We also construct infinite-dimensional spaces of conformal blocks for topological surfaces with smooth boundary. We prove that the conformal blocks satisfy a factorization formula for gluing surfaces along circles, and an analogous formula for gluing surfaces along intervals. We use this interval factorization property to give a new proof of the modularity of the category of representations of a conformal net.

  7. Low Back Pain in Port Machinery Operators

    NASA Astrophysics Data System (ADS)

    BOVENZI, M.; PINTO, I.; STACCHINI, N.

    2002-05-01

    The occurrence of several types of low back pain (LBP) was investigated by a standardized questionnaire in a group of 219 port machinery operators exposed to whole-body vibration (WBV) and postural load and in a control group of 85 maintenance workers employed at the same transport company. The group of port machinery operators included 85 straddle carrier drivers, 88 fork-lift truck drivers, and 46 crane operators. The vector sum of the frequency-weighted r.m.s. acceleration of vibration measured on the seatpan of port vehicles and machines averaged 0·90 m/s2 for fork-lift trucks, 0·48 m/s2 for straddle carriers, 0·53 m/s2 for mobile cranes, and 0·22 m/s2 for overhead cranes. The 12-month prevalence of low back symptoms (LBP, sciatic pain, treated LBP, sick leave due to LBP) was significantly greater in the fork-lift truck drivers than in the controls and the other two groups of port machinery operators. After adjusting for potential confounders, the prevalence of low back symptoms was found to increase with the increase of WBV exposure expressed as duration of exposure (driving years), equivalent vibration magnitude (m/s2), or cumulative vibration exposure (yr m2/s4). An excess risk for lumbar disc herniation was observed in the port machinery operators with prolonged driving experience. In both the controls and the port machinery operators, low back complaints were strongly associated with perceived postural load assessed in terms of frequency and/or duration of awkward postures at work. Multivariate analysis showed that vibration exposure and postural load were independent predictors of LBP. Even though the cross-sectional design of the present study does not permit firm conclusions on the relationship between WBV exposure and low back disorders, the findings of this investigation provide additional epidemiological evidence that seated WBV exposure combined with non-neutral trunk postures, as while driving, is associated with an increased risk of long

  8. Flavin adenine dinucleotide chromophore charge controls the conformation of cyclobutane pyrimidine dimer photolyase α-helices.

    PubMed

    Wijaya, I M Mahaputra; Iwata, Tatsuya; Yamamoto, Junpei; Hitomi, Kenichi; Iwai, Shigenori; Getzoff, Elizabeth D; Kennis, John T M; Mathes, Tilo; Kandori, Hideki

    2014-09-23

    Observations of light-receptive enzyme complexes are usually complicated by simultaneous overlapping signals from the chromophore, apoprotein, and substrate, so that only the initial, ultrafast, photon-chromophore reaction and the final, slow, protein conformational change provide separate, nonoverlapping signals. Each provides its own advantages, whereas sometimes the overlapping signals from the intervening time scales still cannot be fully deconvoluted. We overcome the problem by using a novel method to selectively isotope-label the apoprotein but not the flavin adenine dinucleotide (FAD) cofactor. This allowed the Fourier transform infrared (FTIR) signals to be separated from the apoprotein, FAD cofactor, and DNA substrate. Consequently, a comprehensive structure-function study by FTIR spectroscopy of the Escherichia coli cyclobutane pyrimidine dimer photolyase (CPD-PHR) DNA repair enzyme was possible. FTIR signals could be identified and assigned upon FAD photoactivation and DNA repair, which revealed protein dynamics for both processes beyond simple one-electron reduction and ejection, respectively. The FTIR data suggest that the synergistic cofactor-protein partnership in CPD-PHR linked to changes in the shape of FAD upon one-electron reduction may be coordinated with conformational changes in the apoprotein, allowing it to fit the DNA substrate. Activation of the CPD-PHR chromophore primes the apoprotein for subsequent DNA repair, suggesting that CPD-PHR is not simply an electron-ejecting structure. When FAD is activated, changes in its structure may trigger coordinated conformational changes in the apoprotein and thymine carbonyl of the substrate, highlighting the role of Glu275. In contrast, during DNA repair and release processes, primary conformational changes occur in the enzyme and DNA substrate, with little contribution from the FAD cofactor and surrounding amino acid residues.

  9. Generation of prion transmission barriers by mutational control of amyloid conformations.

    PubMed

    Chien, Peter; DePace, Angela H; Collins, Sean R; Weissman, Jonathan S

    2003-08-21

    Self-propagating beta-sheet-rich protein aggregates are implicated in a wide range of protein-misfolding phenomena, including amyloid diseases and prion-based inheritance. Two properties have emerged as common features of amyloids. Amyloid formation is ubiquitous: many unrelated proteins form such aggregates and even a single polypeptide can misfold into multiple forms--a process that is thought to underlie prion strain variation. Despite this promiscuity, amyloid propagation can be highly sequence specific: amyloid fibres often fail to catalyse the aggregation of other amyloidogenic proteins. In prions, this specificity leads to barriers that limit transmission between species. Using the yeast prion [PSI+], we show in vitro that point mutations in Sup35p, the protein determinant of [PSI+], alter the range of 'infectious' conformations, which in turn changes amyloid seeding specificity. We generate a new transmission barrier in vivo by using these mutations to specifically disfavour subsets of prion strains. The ability of mutations to alter the conformations of amyloid states without preventing amyloid formation altogether provides a general mechanism for the generation of prion transmission barriers and may help to explain how mutations alter toxicity in conformational diseases.

  10. Therapeutic interventions to disrupt the protein synthetic machinery in melanoma.

    PubMed

    Kardos, Gregory R; Robertson, Gavin P

    2015-09-01

    Control of the protein synthetic machinery is deregulated in many cancers, including melanoma, to increase the protein production. Tumor suppressors and oncogenes play key roles in protein synthesis from the transcription of rRNA and ribosome biogenesis to mRNA translation initiation and protein synthesis. Major signaling pathways are altered in melanoma to modulate the protein synthetic machinery, thereby promoting tumor development. However, despite the importance of this process in melanoma development, involvement of the protein synthetic machinery in this cancer type is an underdeveloped area of study. Here, we review the coupling of melanoma development to deregulation of the protein synthetic machinery. We examine existing knowledge regarding RNA polymerase I inhibition and mRNA translation focusing on their inhibition for therapeutic applications in melanoma. Furthermore, the contribution of amino acid biosynthesis and involvement of ribosomal proteins are also reviewed as future therapeutic strategies to target deregulated protein production in melanoma.

  11. Therapeutic Interventions to Disrupt the Protein Synthetic Machinery in Melanoma

    PubMed Central

    Kardos, Gregory R.; Robertson, Gavin P.

    2015-01-01

    Control of the protein synthetic machinery is deregulated in many cancers, including melanoma, in order to increase protein production. Tumor suppressors and oncogenes play key roles in protein synthesis from the transcription of rRNA and ribosome biogenesis to mRNA translation initiation and protein synthesis. Major signaling pathways are altered in melanoma to modulate the protein synthetic machinery thereby promoting tumor development. However, despite the importance of this process in melanoma development, involvement of the protein synthetic machinery in this cancer type is an underdeveloped area of study. Here, we review the coupling of melanoma development to deregulation of the protein synthetic machinery. We examine existing knowledge regarding RNA Polymerase I inhibition and mRNA translation focusing on their inhibition for therapeutic applications in melanoma. Furthermore, the contribution of amino acid biosynthesis and involvement of ribosomal proteins are also reviewed as future therapeutic strategies to target deregulated protein production in melanoma. PMID:26139519

  12. Modeling Molecular Machinery

    ERIC Educational Resources Information Center

    Hunter, Christine

    2015-01-01

    Imagine a microscopic world filled with tiny motors, ratchets, switches, and pumps controlled by complex signaling and feedback systems. Now imagine that these parts can assemble themselves. This is the world presented to students in the protein structure unit of a genetic engineering course. Students learn how protein folding gives rise to the…

  13. Modeling Molecular Machinery

    ERIC Educational Resources Information Center

    Hunter, Christine

    2015-01-01

    Imagine a microscopic world filled with tiny motors, ratchets, switches, and pumps controlled by complex signaling and feedback systems. Now imagine that these parts can assemble themselves. This is the world presented to students in the protein structure unit of a genetic engineering course. Students learn how protein folding gives rise to the…

  14. Practical machinery management for process plants. Volume 3: Machinery component maintenance and repair

    SciTech Connect

    Bloch, H.P.; Geitner, F.K.

    1985-01-01

    This work is a reference for machinery engineers concerned with machinery and component installation, maintenance, and repair. This third volume covers maintenance organization, machinery turnaround management, turbomachinery overhauls, machinery foundations and grouting, process machinery piping, alignment and balancing of machinery components, ball bearing maintenance and replacement, mechanical seals, welded repairs to pump shafts and other rotating equipment components, centrifugal compressor rotor repair, selection and application of O-rings, and more.

  15. Ion-controlled conformational dynamics in the outward-open transition from an occluded state of LeuT.

    PubMed

    Zhao, Chunfeng; Stolzenberg, Sebastian; Gracia, Luis; Weinstein, Harel; Noskov, Sergei; Shi, Lei

    2012-09-05

    Neurotransmitter:sodium symporter (NSS) proteins are secondary Na(+)-driven active transporters that terminate neurotransmission by substrate uptake. Despite the availability of high-resolution crystal structures of a bacterial homolog of NSSs-Leucine Transporter (LeuT)-and extensive computational and experimental structure-function studies, unanswered questions remain regarding the transport mechanisms. We used microsecond atomistic molecular-dynamics (MD) simulations and free-energy computations to reveal ion-controlled conformational dynamics of LeuT in relation to binding affinity and selectivity of the more extracellularly positioned Na(+) binding site (Na1 site). In the course of MD simulations starting from the occluded state with bound Na(+), but in the absence of substrate, we find a spontaneous transition of the extracellular vestibule of LeuT into an outward-open conformation. The outward opening is enhanced by the absence of Na1 and modulated by the protonation state of the Na1-associated Glu-290. Consistently, the Na(+) affinity for the Na1 site is inversely correlated with the extent of outward-open character and is lower than in the occluded state with bound substrate; however, the Na1 site retains its selectivity for Na(+) over K(+) in such conformational transitions. To the best of our knowledge, our findings shed new light on the Na(+)-driven transport cycle and on the symmetry in structural rearrangements for outward- and inward-open transitions.

  16. Use of 1-4 interaction scaling factors to control the conformational equilibrium between α-helix and β-strand.

    PubMed

    Pang, Yuan-Ping

    2015-02-06

    1-4 interaction scaling factors are used in AMBER forcefields to reduce the exaggeration of short-range repulsion caused by the 6-12 Lennard-Jones potential and a nonpolarizable charge model and to obtain better agreements of small-molecule conformational energies with experimental data. However, the effects of these scaling factors on protein secondary structure conformations have not been investigated until now. This article reports the finding that the 1-4 interactions among the protein backbone atoms separated by three consecutive covalent bonds are more repulsive in the α-helix conformation than in two β-strand conformations. Therefore, the 1-4 interaction scaling factors of protein backbone torsions ϕ and ψ control the conformational equilibrium between α-helix and β-strand. Molecular dynamics simulations confirm that reducing the ϕ and ψ scaling factors readily converts the α-helix conformation of AcO-(AAQAA)3-NH2 to a β-strand conformation, and the reverse occurs when these scaling factors are increased. These results suggest that the ϕ and ψ scaling factors can be used to generate the α-helix or β-strand conformation in situ and to control the propensities of a forcefield for adopting secondary structure elements.

  17. Are conformational changes, induced by osmotic pressure variations, the underlying mechanism of controlling the adhesive activity of mussel adhesive proteins?

    PubMed

    van der Leeden, Mieke C

    2005-11-22

    The mussel adhesive protein Mefp-1, under physiological conditions, presumably has a self-avoiding random walk conformation with helix-like or turned deca-peptide segments. Such a conformation may coil up under osmotic pressure induced by surrounding macromolecules. As a consequence, the orientation of the 3,4-dihydroxy-phenylalanine groups (dopa), essential for the adhesive strength as well as the cohesive strength in Mefp-1, will be altered. Changing the concentration of the protein itself or of different-type surrounding macromolecules may therefore be a tool to control the protein's adhesive activity. The effect of osmotic pressure on the conformation and dopa reactivity of Mefp-1 is studied by the addition of (poly)ethylene oxide (PEO) as a model macromolecule (Mw = 100 kD). From UV-spectroscopy measurements, it can be concluded that dopa reactivity in Mefp-1 changes with increasing PEO concentration. Fitting of the measured absorbance intensity data of the oxidation product dopaquinone versus time with a kinetic model points to the decreased accessibility of dopa groups in the Mefp-1 structure, a faster oxidation, and diminished cross linking under the influence of increasing PEO concentration up to 2.4 g/L, corresponding to an osmotic pressure of approximately 73 Pa. At higher PEO concentrations, the accessibility of the dopa groups for oxidation as well as cross-link formation decreases until about 20% of the dopa groups are oxidized at a PEO concentration of 3.8 g/L, corresponding to an osmotic pressure of approximately 113 Pa. FTIR measurements on the basis of amide I shifts qualitatively point to a transition to a more continuously turned structure of Mefp-1 in the presence of PEO. Therefore, it seems that conformational changes caused by variations of osmotic pressure determine the extent of steric hindrance of the dopa groups and hence the adhesive reactivity of Mefp-1.

  18. Tractor & Machinery Safety. 1984 Revision.

    ERIC Educational Resources Information Center

    Montana State Office of Public Instruction, Helena. Dept. of Vocational Education Services.

    This curriculum guide is intended for use in teaching an instructional unit in tractor and machinery safety that is geared toward college freshmen. Addressed in the individual lessons of the unit are the following topics: understanding the importance of safe and efficient tractor operation, understanding the characteristics of tractors, preparing…

  19. Conformational dynamics of helix 8 in the GPCR rhodopsin controls arrestin activation in the desensitization process

    PubMed Central

    Kirchberg, Kristina; Kim, Tai-Yang; Möller, Martina; Skegro, Darko; Dasara Raju, Gayathri; Granzin, Joachim; Büldt, Georg; Schlesinger, Ramona; Alexiev, Ulrike

    2011-01-01

    Arrestins are regulatory molecules for G-protein coupled receptor function. In visual rhodopsin, selective binding of arrestin to the cytoplasmic side of light-activated, phosphorylated rhodopsin (P-Rh*) terminates signaling via the G-protein transducin. While the “phosphate-sensor” of arrestin for the recognition of receptor-attached phosphates is identified, the molecular mechanism of arrestin binding and the involvement of receptor conformations in this process are still largely hypothetic. Here we used fluorescence pump-probe and time-resolved fluorescence depolarization measurements to investigate the kinetics of arrestin conformational changes and the corresponding nanosecond dynamical changes at the receptor surface. We show that at least two sequential conformational changes of arrestin occur upon interaction with P-Rh*, thus providing a kinetic proof for the suggested multistep nature of arrestin binding. At the cytoplasmic surface of P-Rh*, the structural dynamics of the amphipathic helix 8 (H8), connecting transmembrane helix 7 and the phosphorylated C-terminal tail, depends on the arrestin interaction state. We find that a high mobility of H8 is required in the low-affinity (prebinding) but not in the high-affinity binding state. High-affinity arrestin binding is inhibited when a bulky, inflexible group is bound to H8, indicating close interaction. We further show that this close steric interaction of H8 with arrestin is mandatory for the transition from prebinding to high-affinity binding; i.e., for arrestin activation. This finding implies a regulatory role for H8 in activation of visual arrestin, which shows high selectivity to P-Rh* in contrast to the broad receptor specificity displayed by the two nonvisual arrestins. PMID:22039220

  20. Calcium-controlled conformational choreography in the N-terminal half of adseverin

    PubMed Central

    Chumnarnsilpa, Sakesit; Robinson, Robert C.; Grimes, Jonathan M.; Leyrat, Cedric

    2015-01-01

    Adseverin is a member of the calcium-regulated gelsolin superfamily of actin-binding proteins. Here we report the crystal structure of the calcium-free N-terminal half of adseverin (iA1–A3) and the Ca2+-bound structure of A3, which reveal structural similarities and differences with gelsolin. Solution small-angle X-ray scattering combined with ensemble optimization revealed a dynamic Ca2+-dependent equilibrium between inactive, intermediate and active conformations. Increasing calcium concentrations progressively shift this equilibrium from a main population of inactive conformation to the active form. Molecular dynamics simulations of iA1–A3 provided insights into Ca2+-induced destabilization, implicating a critical role for the A2 type II calcium-binding site and the A2A3 linker in the activation process. Finally, mutations that disrupt the A1/A3 interface increase Ca2+-independent F-actin severing by A1–A3, albeit at a lower efficiency than observed for gelsolin domains G1–G3. Together, these data address the calcium dependency of A1–A3 activity in relation to the calcium-independent activity of G1–G3. PMID:26365202

  1. Molecular conformation-controlled vesicle/micelle transition of cationic trimeric surfactants in aqueous solution.

    PubMed

    Wu, Chunxian; Hou, Yanbo; Deng, Manli; Huang, Xu; Yu, Defeng; Xiang, Junfeng; Liu, Yu; Li, Zhibo; Wang, Yilin

    2010-06-01

    Two star-like trimeric cationic surfactants with amide groups in spacers, tri(dodecyldimethylammonioacetoxy)diethyltriamine trichloride (DTAD) and tri(dodecyldimethylammonioacetoxy)tris(2-aminoethyl)amine trichloride (DDAD), have been synthesized, and the aggregation behavior of the surfactants in aqueous solution has been investigated by surface tension, electrical conductivity, isothermal titration microcalorimetry, dynamic light scattering, cryogenic transmission electron microscopy, and NMR techniques. Typically, both the surfactants form vesicles just above critical aggregation concentration (CAC), and then the vesicles transfer to micelles gradually with an increase of the surfactant concentration. It is approved that the conformation of the surfactant molecules changes in this transition process. Just above the CAC, the hydrophobic chains of the surfactant molecules pack more loosely because of the rigid spacer and intramolecular electrostatic repulsion in the three-charged headgroup. With the increase of the surfactant concentration, hydrophobic interaction becomes strong enough to pack the hydrophobic tails tightly and turn the molecular conformation into a pyramid-like shape, thus leading to the vesicle to micelle transition.

  2. Silver ions-mediated conformational switch: facile design of structure-controllable nucleic acid probes.

    PubMed

    Wang, Yongxiang; Li, Jishan; Wang, Hao; Jin, Jianyu; Liu, Jinhua; Wang, Kemin; Tan, Weihong; Yang, Ronghua

    2010-08-01

    Conformationally constraint nucleic acid probes were usually designed by forming an intramolecular duplex based on Watson-Crick hydrogen bonds. The disadvantages of these approaches are the inflexibility and instability in complex environment of the Watson-Crick-based duplex. We report that this hydrogen bonding pattern can be replaced by metal-ligation between specific metal ions and the natural bases. To demonstrate the feasibility of this principle, two linear oligonucleotides and silver ions were examined as models for DNA hybridization assay and adenosine triphosphate detection. The both nucleic acids contain target binding sequences in the middle and cytosine (C)-rich sequences at the lateral portions. The strong interaction between Ag(+) ions and cytosines forms stable C-Ag(+)-C structures, which promises the oligonucleotides to form conformationally constraint formations. In the presence of its target, interaction between the loop sequences and the target unfolds the C-Ag(+)-C structures, and the corresponding probes unfolding can be detected by a change in their fluorescence emission. We discuss the thermodynamic and kinetic opportunities that are provided by using Ag(+) ion complexes instead of traditional Watson-Crick-based duplex. In particular, the intrinsic feature of the metal-ligation motif facilitates the design of functional nucleic acids probes by independently varying the concentration of Ag(+) ions in the medium.

  3. Conformational Changes Involving Ammonia Tunnel Formation and Allosteric Control in GMP Synthetase

    PubMed Central

    Oliver, Justin C.; Gudihal, Ravidra; Burgner, John W.; Pedley, Anthony M.; Zwierko, Alexander T.; Davisson, V. Jo; Linger, Rebecca S.

    2014-01-01

    GMP synthetase is the glutamine amidotransferase that catalyzes the final step in the guanylate branch of de novo purine biosynthesis. Conformational changes are required to efficiently couple distal active sites in the protein; however, the nature of these changes has remained elusive. Structural information derived from both limited proteolysis and sedimentation velocity experiments support the hypothesis of nucleotide-induced loop- and domain-closure in the protein. These results were combined with information from sequence conservation and precedents from other glutamine amidotransferases to develop the first structural model of GMPS in a closed, active state. In analyzing this Catalytic model, an interdomain salt bridge was identified residing in the same location as seen in other triad glutamine amidotransferases. Using mutagenesis and kinetic analysis, the salt bridge between H186 and E383 was shown to function as a connection between the two active sites. Mutations at these residues uncoupled the two half-reactions of the enzyme. The chemical events of nucleotide binding initiate a series of conformational changes that culminate in the establishment of a tunnel for ammonia as well as an activated glutaminase catalytic site. The results of this study provide a clearer understanding of the allostery of GMPS, where, for the first time, key substrate binding and interdomain contacts are modeled and analyzed. PMID:24434004

  4. Force-dependent conformational switch of α-catenin controls vinculin binding

    NASA Astrophysics Data System (ADS)

    Yao, Mingxi; Qiu, Wu; Liu, Ruchuan; Efremov, Artem K.; Cong, Peiwen; Seddiki, Rima; Payre, Manon; Lim, Chwee Teck; Ladoux, Benoit; Mège, René-Marc; Yan, Jie

    2014-07-01

    Force sensing at cadherin-mediated adhesions is critical for their proper function. α-Catenin, which links cadherins to actomyosin, has a crucial role in this mechanosensing process. It has been hypothesized that force promotes vinculin binding, although this has never been demonstrated. X-ray structure further suggests that α-catenin adopts a stable auto-inhibitory conformation that makes the vinculin-binding site inaccessible. Here, by stretching single α-catenin molecules using magnetic tweezers, we show that the subdomains MI vinculin-binding domain (VBD) to MIII unfold in three characteristic steps: a reversible step at ~5 pN and two non-equilibrium steps at 10-15 pN. 5 pN unfolding forces trigger vinculin binding to the MI domain in a 1:1 ratio with nanomolar affinity, preventing MI domain refolding after force is released. Our findings demonstrate that physiologically relevant forces reversibly unfurl α-catenin, activating vinculin binding, which then stabilizes α-catenin in its open conformation, transforming force into a sustainable biochemical signal.

  5. Calcium-controlled conformational choreography in the N-terminal half of adseverin

    NASA Astrophysics Data System (ADS)

    Chumnarnsilpa, Sakesit; Robinson, Robert C.; Grimes, Jonathan M.; Leyrat, Cedric

    2015-09-01

    Adseverin is a member of the calcium-regulated gelsolin superfamily of actin-binding proteins. Here we report the crystal structure of the calcium-free N-terminal half of adseverin (iA1-A3) and the Ca2+-bound structure of A3, which reveal structural similarities and differences with gelsolin. Solution small-angle X-ray scattering combined with ensemble optimization revealed a dynamic Ca2+-dependent equilibrium between inactive, intermediate and active conformations. Increasing calcium concentrations progressively shift this equilibrium from a main population of inactive conformation to the active form. Molecular dynamics simulations of iA1-A3 provided insights into Ca2+-induced destabilization, implicating a critical role for the A2 type II calcium-binding site and the A2A3 linker in the activation process. Finally, mutations that disrupt the A1/A3 interface increase Ca2+-independent F-actin severing by A1-A3, albeit at a lower efficiency than observed for gelsolin domains G1-G3. Together, these data address the calcium dependency of A1-A3 activity in relation to the calcium-independent activity of G1-G3.

  6. Calcium-controlled conformational choreography in the N-terminal half of adseverin.

    PubMed

    Chumnarnsilpa, Sakesit; Robinson, Robert C; Grimes, Jonathan M; Leyrat, Cedric

    2015-09-14

    Adseverin is a member of the calcium-regulated gelsolin superfamily of actin-binding proteins. Here we report the crystal structure of the calcium-free N-terminal half of adseverin (iA1-A3) and the Ca(2+)-bound structure of A3, which reveal structural similarities and differences with gelsolin. Solution small-angle X-ray scattering combined with ensemble optimization revealed a dynamic Ca(2+)-dependent equilibrium between inactive, intermediate and active conformations. Increasing calcium concentrations progressively shift this equilibrium from a main population of inactive conformation to the active form. Molecular dynamics simulations of iA1-A3 provided insights into Ca(2+)-induced destabilization, implicating a critical role for the A2 type II calcium-binding site and the A2A3 linker in the activation process. Finally, mutations that disrupt the A1/A3 interface increase Ca(2+)-independent F-actin severing by A1-A3, albeit at a lower efficiency than observed for gelsolin domains G1-G3. Together, these data address the calcium dependency of A1-A3 activity in relation to the calcium-independent activity of G1-G3.

  7. Modulation of Multiscale 3D Lattices through Conformational Control: Painting Silk Inverse Opals with Water and Light.

    PubMed

    Wang, Yu; Aurelio, Daniele; Li, Wenyi; Tseng, Peter; Zheng, Zhaozhu; Li, Meng; Kaplan, David L; Liscidini, Marco; Omenetto, Fiorenzo G

    2017-10-01

    Structural proteins from naturally occurring materials are an inspiring template for material design and synthesis at multiple scales. The ability to control the assembly and conformation of such materials offers the opportunity to define fabrication approaches that recapitulate the dimensional hierarchy and structure-function relationships found in nature. A simple and versatile directed assembly method of silk fibroin, which allows the design of structures across multiple dimensional scales by generating and tuning structural color in large-scale, macro defect-free colloidally assembled 3D nanostructures in the form of silk inverse opals (SIOs) is reported. This approach effectively combines bottom-up and top-down techniques to obtain control on the nanoscale (through silk conformational changes), microscale (through patterning), and macroscale (through colloidal assembly), ultimately resulting in a controllable photonic lattice with predefined spectral behavior, with a resulting palette spanning almost the entire visible range. As a demonstration of the approach, examples of "multispectral" SIOs, paired with theoretical calculations and analysis of their response as a function of changes of lattice constants and refractive index contrast are illustrated. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. A Coiled-coil Clamp Controls Both Conformation and Clustering of Stromal Interaction Molecule 1 (STIM1)*

    PubMed Central

    Fahrner, Marc; Muik, Martin; Schindl, Rainer; Butorac, Carmen; Stathopulos, Peter; Zheng, Le; Jardin, Isaac; Ikura, Mitsuhiko; Romanin, Christoph

    2014-01-01

    Store-operated Ca2+ entry, essential for the adaptive immunity, is initiated by the endoplasmic reticulum (ER) Ca2+ sensor STIM1. Ca2+ entry occurs through the plasma membrane resident Ca2+ channel Orai1 that directly interacts with the C-terminal STIM1 domain, named SOAR/CAD. Depletion of the ER Ca2+ store controls this STIM1/Orai1 interaction via transition to an extended STIM1 C-terminal conformation, exposure of the SOAR/CAD domain, and STIM1/Orai1 co-clustering. Here we developed a novel approach termed FRET-derived Interaction in a Restricted Environment (FIRE) in an attempt to dissect the interplay of coiled-coil (CC) interactions in controlling STIM1 quiescent as well as active conformation and cluster formation. We present evidence of a sequential activation mechanism in the STIM1 cytosolic domains where the interaction between CC1 and CC3 segment regulates both SOAR/CAD exposure and CC3-mediated higher-order oligomerization as well as cluster formation. These dual levels of STIM1 auto-inhibition provide efficient control over the coupling to and activation of Orai1 channels. PMID:25342749

  9. Budding yeast ATM/ATR control meiotic double-strand break (DSB) levels by down-regulating Rec114, an essential component of the DSB-machinery.

    PubMed

    Carballo, Jesús A; Panizza, Silvia; Serrentino, Maria Elisabetta; Johnson, Anthony L; Geymonat, Marco; Borde, Valérie; Klein, Franz; Cha, Rita S

    2013-06-01

    An essential feature of meiosis is Spo11 catalysis of programmed DNA double strand breaks (DSBs). Evidence suggests that the number of DSBs generated per meiosis is genetically determined and that this ability to maintain a pre-determined DSB level, or "DSB homeostasis", might be a property of the meiotic program. Here, we present direct evidence that Rec114, an evolutionarily conserved essential component of the meiotic DSB-machinery, interacts with DSB hotspot DNA, and that Tel1 and Mec1, the budding yeast ATM and ATR, respectively, down-regulate Rec114 upon meiotic DSB formation through phosphorylation. Mimicking constitutive phosphorylation reduces the interaction between Rec114 and DSB hotspot DNA, resulting in a reduction and/or delay in DSB formation. Conversely, a non-phosphorylatable rec114 allele confers a genome-wide increase in both DSB levels and in the interaction between Rec114 and the DSB hotspot DNA. These observations strongly suggest that Tel1 and/or Mec1 phosphorylation of Rec114 following Spo11 catalysis down-regulates DSB formation by limiting the interaction between Rec114 and DSB hotspots. We also present evidence that Ndt80, a meiosis specific transcription factor, contributes to Rec114 degradation, consistent with its requirement for complete cessation of DSB formation. Loss of Rec114 foci from chromatin is associated with homolog synapsis but independent of Ndt80 or Tel1/Mec1 phosphorylation. Taken together, we present evidence for three independent ways of regulating Rec114 activity, which likely contribute to meiotic DSBs-homeostasis in maintaining genetically determined levels of breaks.

  10. A conformal mapping based fractional order approach for sub-optimal tuning of PID controllers with guaranteed dominant pole placement

    NASA Astrophysics Data System (ADS)

    Saha, Suman; Das, Saptarshi; Das, Shantanu; Gupta, Amitava

    2012-09-01

    A novel conformal mapping based fractional order (FO) methodology is developed in this paper for tuning existing classical (Integer Order) Proportional Integral Derivative (PID) controllers especially for sluggish and oscillatory second order systems. The conventional pole placement tuning via Linear Quadratic Regulator (LQR) method is extended for open loop oscillatory systems as well. The locations of the open loop zeros of a fractional order PID (FOPID or PIλDμ) controller have been approximated in this paper vis-à-vis a LQR tuned conventional integer order PID controller, to achieve equivalent integer order PID control system. This approach eases the implementation of analog/digital realization of a FOPID controller with its integer order counterpart along with the advantages of fractional order controller preserved. It is shown here in the paper that decrease in the integro-differential operators of the FOPID/PIλDμ controller pushes the open loop zeros of the equivalent PID controller towards greater damping regions which gives a trajectory of the controller zeros and dominant closed loop poles. This trajectory is termed as "M-curve". This phenomena is used to design a two-stage tuning algorithm which reduces the existing PID controller's effort in a significant manner compared to that with a single stage LQR based pole placement method at a desired closed loop damping and frequency.

  11. Allosteric regulation of SecA: magnesium-mediated control of conformation and activity.

    PubMed

    Gold, Vicki A M; Robson, Alice; Clarke, Anthony R; Collinson, Ian

    2007-06-15

    In bacteria, the SecA protein associates with a ubiquitous protein channel SecYEG where it drives the post-translational secretion of pre-proteins across the plasma membrane. The high-resolution structures of both proteins have been determined in their resting states; however, the mechanism that couples ATP hydrolysis to active transport of substrate proteins through the membrane is not well understood. An analysis of the steady-state ATPase activity of the enzyme reveals that there is an allosteric binding site for magnesium distinct from that associated with hydrolysis of ATP. We have demonstrated that this regulation involves a large conformational change to the SecA dimer, which exerts a strong influence on the turnover and affinity for ATP, as well as the affinity for ADP. The strong inhibitory influence of magnesium on the ATPase activity can be countered by cardiolipin and conditions that promote protein translocation.

  12. Controlled orientation of substitution in betaines. Synthesis and conformational analysis of new heterocyclic compounds with phosphorus

    SciTech Connect

    Kochkanyan, R.O.; Dmitruk, T.A.; Korzhenevskaya, N.G.; Lukanyuk, S.S.

    1985-07-01

    The orientation of nucleophilic substitution in betaines and ylides, which also include nucleotides, has certain features that are due to the presence of charges. In this work it was found that azole betaines containing a heteroaromatic cation and a formyl group in the anionic part, when protonated by mineral acids, react with triphenylphosphine to replace the cation with triphenylphosphonium to form 4-triphenylphosphonium-5-formylazolinones. In acetic acid the cation is replaced by the oxygen of the formyl group, by a sigmatropic rearrangement, to form new bicyclic systems of the oxaphospholeno(4,5-d)azolinone type. Conditions were found for the formation of the trans-(E) and cis-(Z) isomers of 1-phenyl-5-triphenylphosphoniummethylidenimidazolidin-2,4-dione perchlorate, and their conformational analysis is shown.

  13. Control of the conformations of ion Coulomb crystals in a Penning trap

    PubMed Central

    Mavadia, Sandeep; Goodwin, Joseph F.; Stutter, Graham; Bharadia, Shailen; Crick, Daniel R.; Segal, Daniel M.; Thompson, Richard C.

    2013-01-01

    Laser-cooled atomic ions form ordered structures in radiofrequency ion traps and in Penning traps. Here we demonstrate in a Penning trap the creation and manipulation of a wide variety of ion Coulomb crystals formed from small numbers of ions. The configuration can be changed from a linear string, through intermediate geometries, to a planar structure. The transition from a linear string to a zigzag geometry is observed for the first time in a Penning trap. The conformations of the crystals are set by the applied trap potential and the laser parameters, and agree with simulations. These simulations indicate that the rotation frequency of a small crystal is mainly determined by the laser parameters, independent of the number of ions and the axial confinement strength. This system has potential applications for quantum simulation, quantum information processing and tests of fundamental physics models from quantum field theory to cosmology. PMID:24096901

  14. 30 CFR 57.14204 - Machinery lubrication.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Machinery lubrication. 57.14204 Section 57.14204 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL... Equipment Safety Practices and Operational Procedures § 57.14204 Machinery lubrication. Machinery...

  15. 30 CFR 56.14204 - Machinery lubrication.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Machinery lubrication. 56.14204 Section 56.14204 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL... Equipment Safety Practices and Operational Procedures § 56.14204 Machinery lubrication. Machinery...

  16. Transportation Conformity

    EPA Pesticide Factsheets

    This section provides information on: current laws, regulations and guidance, policy and technical guidance, project-level conformity, general information, contacts and training, adequacy review of SIP submissions

  17. Aβ peptide fibrillar architectures controlled by conformational constraints of the monomer.

    PubMed

    Brännström, Kristoffer; Ohman, Anders; Olofsson, Anders

    2011-01-01

    Anomalous self-assembly of the Aβ peptide into fibrillar amyloid deposits is strongly correlated with the development of Alzheimer's disease. Aβ fibril extension follows a template guided "dock and lock" mechanism where polymerisation is catalysed by the fibrillar ends. Using surface plasmon resonance (SPR) and quenched hydrogen-deuterium exchange NMR (H/D-exchange NMR), we have analysed the fibrillar structure and polymerisation properties of both the highly aggregation prone Aβ1-40 Glu22Gly (Aβ(40Arc)) and wild type Aβ1-40 (Aβ(40WT)). The solvent protection patterns from H/D exchange experiments suggest very similar structures of the fibrillar forms. However, through cross-seeding experiments monitored by SPR, we found that the monomeric form of Aβ(40WT) is significantly impaired to acquire the fibrillar architecture of Aβ(40Arc). A detailed characterisation demonstrated that Aβ(40WT) has a restricted ability to dock and isomerise with high binding affinity onto Aβ(40Arc) fibrils. These results have general implications for the process of fibril assembly, where the rate of polymerisation, and consequently the architecture of the formed fibrils, is restricted by conformational constraints of the monomers. Interestingly, we also found that the kinetic rate of fibril formation rather than the thermodynamically lowest energy state determines the overall fibrillar structure.

  18. Salt-bridge dynamics control substrate-induced conformational change in the membrane transporter GlpT.

    PubMed

    Law, Christopher J; Almqvist, Jonas; Bernstein, Adam; Goetz, Regina M; Huang, Yafei; Soudant, Celine; Laaksonen, Aatto; Hovmöller, Sven; Wang, Da-Neng

    2008-05-09

    Active transport of substrates across cytoplasmic membranes is of great physiological, medical and pharmaceutical importance. The glycerol-3-phosphate (G3P) transporter (GlpT) of the E. coli inner membrane is a secondary active antiporter from the ubiquitous major facilitator superfamily that couples the import of G3P to the efflux of inorganic phosphate (P(i)) down its concentration gradient. Integrating information from a novel combination of structural, molecular dynamics simulations and biochemical studies, we identify the residues involved directly in binding of substrate to the inward-facing conformation of GlpT, thus defining the structural basis for the substrate-specificity of this transporter. The substrate binding mechanism involves protonation of a histidine residue at the binding site. Furthermore, our data suggest that the formation and breaking of inter- and intradomain salt bridges control the conformational change of the transporter that accompanies substrate translocation across the membrane. The mechanism we propose may be a paradigm for organophosphate:phosphate antiporters.

  19. Essentials of Proteolytic Machineries in Chloroplasts.

    PubMed

    Nishimura, Kenji; Kato, Yusuke; Sakamoto, Wataru

    2017-01-09

    Plastids are unique organelles that can alter their structure and function in response to environmental and developmental stimuli. Chloroplasts are one type of plastid and are the sites for various metabolic processes, including photosynthesis. For optimal photosynthetic activity, the chloroplast proteome must be properly shaped and maintained through regulated proteolysis and protein quality control mechanisms. Enzymatic functions and activities are conferred by protein maturation processes involving consecutive proteolytic reactions. Protein abundances are optimized by the balanced protein synthesis and degradation, which is depending on the metabolic status. Malfunctioning proteins are promptly degraded. Twenty chloroplast proteolytic machineries have been characterized to date. Specifically, processing peptidases and energy-driven processive proteases are the major players in chloroplast proteome biogenesis, remodeling, and maintenance. Recently identified putative proteases are potential regulators of photosynthetic functions. Here we provide an updated, comprehensive overview of chloroplast protein degradation machineries and discuss their importance for photosynthesis. Wherever possible, we also provide structural insights into chloroplast proteases that implement regulated proteolysis of substrate proteins/peptides. Copyright © 2017 The Author. Published by Elsevier Inc. All rights reserved.

  20. On the mechanochemical machinery underlying chromatin remodeling

    NASA Astrophysics Data System (ADS)

    Yusufaly, Tahir I.

    This dissertation discuss two recent efforts, via a unique combination of structural bioinformatics and density functional theory, to unravel some of the details concerning how molecular machinery within the eukaryotic cell nucleus controls chromatin architecture. The first, a study of the 5-methylation of cytosine in 5'-CG-3' : 5'-CG-3' base-pair steps, reveals that the methyl groups roughen the local elastic energy landscape of the DNA. This enhances the probability of the canonical B-DNA structure transitioning into the undertwisted A-like and overtwisted C-like forms seen in nucleosomes, or looped segments of DNA bound to histones. The second part focuses on the formation of salt bridges between arginine residues in histones and phosphate groups on the DNA backbone. The arginine residues are ob- served to apply a tunable mechanical load to the backbone, enabling precision-controlled activation of DNA deformations.

  1. Inhibition of cullin RING ligases by cycle inhibiting factor: evidence for interference with Nedd8-induced conformational control.

    PubMed

    Boh, Boon Kim; Ng, Mei Ying; Leck, Yee Chin; Shaw, Barry; Long, Jed; Sun, Guang Wen; Gan, Yunn Hwen; Searle, Mark S; Layfield, Robert; Hagen, Thilo

    2011-10-21

    Cycle inhibiting factor (Cif) is produced by pathogenic intracellular bacteria and injected into the host cells via a type III secretion system. Cif is known to interfere with the eukaryotic cell cycle by inhibiting the function of cullin RING E3 ubiquitin ligases (CRLs). Cullin proteins form the scaffold protein of CRLs and are modified with the ubiquitin-like protein Nedd8, which exerts important conformational control required for CRL activity. Cif has recently been shown to catalyze the deamidation of Gln40 in Nedd8 to Glu. Here, we addressed how Nedd8 deamidation inhibits CRL activity. Our results indicate that Burkholderia pseudomallei Cif (also known as CHBP) inhibits the deconjugation of Nedd8 in vivo by inhibiting binding of the deneddylating COP9 signalosome (CSN) complex. We provide evidence that the reduced binding of CSN and the inhibition of CRL activity by Cif are due to interference with Nedd8-induced conformational control, which is dependent on the interaction between the Nedd8 hydrophobic patch and the cullin winged-helix B subdomain. Of note, mutation of Gln40 to Glu in ubiquitin, an additional target of Cif, inhibits the interaction between the hydrophobic surface of ubiquitin and the ubiquitin-binding protein p62/SQSTM1, showing conceptually that Cif activity can impair ubiquitin/ubiquitin-like protein non-covalent interactions. Our results also suggest that Cif may exert additional cellular effects by interfering with the association between ubiquitin and ubiquitin-binding proteins. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Conformational diversity of flexible ligand in metal-organic frameworks controlled by size-matching mixed ligands

    SciTech Connect

    Hua, Xiu-Ni; Qin, Lan; Yan, Xiao-Zhi; Yu, Lei; Xie, Yi-Xin; Han, Lei

    2015-12-15

    Hydrothermal reactions of N-auxiliary flexible exo-bidentate ligand 1,3-bis(4-pyridyl)propane (bpp) and carboxylates ligands naphthalene-2,6-dicarboxylic acid (2,6-H{sub 2}ndc) or 4,4′-(hydroxymethylene)dibenzoic acid (H{sub 2}hmdb), in the presence of cadmium(II) salts have given rise to two novel metal-organic frameworks based on flexible ligands (FL-MOFs), namely, [Cd{sub 2}(2,6-ndc){sub 2}(bpp)(DMF)]·2DMF (1) and [Cd{sub 3}(hmdb){sub 3}(bpp)]·2DMF·2EtOH (2) (DMF=N,N-Dimethylformamide). Single-crystal X-ray diffraction analyses revealed that compound 1 exhibits a three-dimensional self-penetrating 6-connected framework based on dinuclear cluster second building unit. Compound 2 displays an infinite three-dimensional ‘Lucky Clover’ shape (2,10)-connected network based on the trinuclear cluster and V-shaped organic linkers. The flexible bpp ligand displays different conformations in 1 and 2, which are successfully controlled by size-matching mixed ligands during the self-assembly process. - Graphical abstract: Compound 1 exhibits a 3D self-penetrating 6-connected framework based on dinuclear cluster, and 2 displays an infinite 3D ‘Lucky Clover’ shape (2,10)-connected network based on the trinuclear cluster. The flexible 1,3-bis(4-pyridyl)propane ligand displays different conformations in 1 and 2, which successfully controlled by size-matching mixed ligands during the self-assembly process.

  3. The structure of the β-barrel assembly machinery complex

    SciTech Connect

    Bakelar, Jeremy; Buchanan, Susan K.; Noinaj, Nicholas

    2016-01-08

    β-Barrel outer membrane proteins (OMPs) are found in the outer membranes of Gram-negative bacteria and are essential for nutrient import, signaling, and adhesion. A 200-kilodalton five-component complex called the β-barrel assembly machinery (BAM) complex has been implicated in the biogenesis of OMPs. In this paper, we report the structure of the BAM complex from Escherichia coli, revealing that binding of BamCDE modulates the conformation of BamA, the central component, which may serve to regulate the BAM complex. The periplasmic domain of BamA was in a closed state that prevents access to the barrel lumen, which indicates substrate OMPs may not be threaded through the barrel during biogenesis. Finally and further, conformational shifts in the barrel domain lead to opening of the exit pore and rearrangement at the lateral gate.

  4. An allosteric photoredox catalyst inspired by photosynthetic machinery.

    PubMed

    Lifschitz, Alejo M; Young, Ryan M; Mendez-Arroyo, Jose; Stern, Charlotte L; McGuirk, C Michael; Wasielewski, Michael R; Mirkin, Chad A

    2015-03-30

    Biological photosynthetic machinery allosterically regulate light harvesting via conformational and electronic changes at the antenna protein complexes as a response to specific chemical inputs. Fundamental limitations in current approaches to regulating inorganic light-harvesting mimics prevent their use in catalysis. Here we show that a light-harvesting antenna/reaction centre mimic can be regulated by utilizing a coordination framework incorporating antenna hemilabile ligands and assembled via a high-yielding, modular approach. As in nature, allosteric regulation is afforded by coupling the conformational changes to the disruptions in the electrochemical landscape of the framework upon recognition of specific coordinating analytes. The hemilabile ligands enable switching using remarkably mild and redox-inactive inputs, allowing one to regulate the photoredox catalytic activity of the photosynthetic mimic reversibly and in situ. Thus, we demonstrate that bioinspired regulatory mechanisms can be applied to inorganic light-harvesting arrays displaying switchable catalytic properties and with potential uses in solar energy conversion and photonic devices.

  5. The structure of the β-barrel assembly machinery complex

    DOE PAGES

    Bakelar, Jeremy; Buchanan, Susan K.; Noinaj, Nicholas

    2016-01-08

    β-Barrel outer membrane proteins (OMPs) are found in the outer membranes of Gram-negative bacteria and are essential for nutrient import, signaling, and adhesion. A 200-kilodalton five-component complex called the β-barrel assembly machinery (BAM) complex has been implicated in the biogenesis of OMPs. In this paper, we report the structure of the BAM complex from Escherichia coli, revealing that binding of BamCDE modulates the conformation of BamA, the central component, which may serve to regulate the BAM complex. The periplasmic domain of BamA was in a closed state that prevents access to the barrel lumen, which indicates substrate OMPs may notmore » be threaded through the barrel during biogenesis. Finally and further, conformational shifts in the barrel domain lead to opening of the exit pore and rearrangement at the lateral gate.« less

  6. 46 CFR 111.103-9 - Machinery stop stations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...-GENERAL REQUIREMENTS Remote Stopping Systems § 111.103-9 Machinery stop stations. (a) Each forced draft fan, induced draft fan, blower of an inert gas system, fuel oil transfer pump, fuel oil unit, fuel oil service pump, and any other fuel oil pumps must have a stop control that is outside of the...

  7. 46 CFR 28.840 - Means for stopping pumps, ventilation, and machinery.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 1 2013-10-01 2013-10-01 false Means for stopping pumps, ventilation, and machinery. 28... pumps, ventilation, and machinery. All electrically driven fuel oil transfer pumps, fuel oil unit and service pumps, and ventilation fans shall be fitted with remote controls from a readily...

  8. 46 CFR 28.840 - Means for stopping pumps, ventilation, and machinery.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 1 2012-10-01 2012-10-01 false Means for stopping pumps, ventilation, and machinery. 28... pumps, ventilation, and machinery. All electrically driven fuel oil transfer pumps, fuel oil unit and service pumps, and ventilation fans shall be fitted with remote controls from a readily...

  9. 46 CFR 28.840 - Means for stopping pumps, ventilation, and machinery.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 1 2014-10-01 2014-10-01 false Means for stopping pumps, ventilation, and machinery. 28... pumps, ventilation, and machinery. All electrically driven fuel oil transfer pumps, fuel oil unit and service pumps, and ventilation fans shall be fitted with remote controls from a readily...

  10. 46 CFR 28.840 - Means for stopping pumps, ventilation, and machinery.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 1 2011-10-01 2011-10-01 false Means for stopping pumps, ventilation, and machinery. 28... pumps, ventilation, and machinery. All electrically driven fuel oil transfer pumps, fuel oil unit and service pumps, and ventilation fans shall be fitted with remote controls from a readily...

  11. Conforming to partnership values: a qualitative case study of public–private mix for TB control in Ghana

    PubMed Central

    Amo-Adjei, Joshua

    2016-01-01

    Background Public–private mix (PPM) can supplement public sector initiatives, including public health. As National Tuberculosis Control Programmes around the world embrace PPM, conforming to the four key principles of partnership values of beneficence, non-maleficence, autonomy, and equity as espoused by the World Health Organization can provide a useful framework to guide successful implementation. Design This is a qualitative case study of PPM in tuberculosis (TB) control, which utilised a purposive sample of 30 key stakeholders involved in TB control in Ghana. Respondents comprised an equal number of respondents from both the public and private sectors. Semi-structured in-depth interviews (IDI) were conducted with respondents. Data emanating from the IDIs were analysed deductively. Results Although the respondents’ perceptions about beneficence were unanimous, their views about non-maleficence, autonomy, and equity appeared incongruous with the underlying meanings of the PPM values. Underlying the unfavourable perceptions were disruptions in funding, project implementers’ failure to follow-up on promised incentives, and private providers lost interest. This was perceived to have negatively affected the smooth implementation of PPM in the country. Conclusions Going forward, it is imperative that future partnerships are built around utilitarian principles and also adhere to the dictates of agreements, whether they are ‘soft’ or standard contracts. PMID:26739783

  12. Size-controlled conformal nanofabrication of biotemplated three-dimensional TiO2 and ZnO nanonetworks

    PubMed Central

    Ceylan, Hakan; Ozgit-Akgun, Cagla; Erkal, Turan S.; Donmez, Inci; Garifullin, Ruslan; Tekinay, Ayse B.; Usta, Hakan; Biyikli, Necmi; Guler, Mustafa O.

    2013-01-01

    A solvent-free fabrication of TiO2 and ZnO nanonetworks is demonstrated by using supramolecular nanotemplates with high coating conformity, uniformity, and atomic scale size control. Deposition of TiO2 and ZnO on three-dimensional nanofibrous network template is accomplished. Ultrafine control over nanotube diameter allows robust and systematic evaluation of the electrochemical properties of TiO2 and ZnO nanonetworks in terms of size-function relationship. We observe hypsochromic shift in UV absorbance maxima correlated with decrease in wall thickness of the nanotubes. Photocatalytic activities of anatase TiO2 and hexagonal wurtzite ZnO nanonetworks are found to be dependent on both the wall thickness and total surface area per unit of mass. Wall thickness has effect on photoexcitation properties of both TiO2 and ZnO due to band gap energies and total surface area per unit of mass. The present work is a successful example that concentrates on nanofabrication of intact three-dimensional semiconductor nanonetworks with controlled band gap energies. PMID:23892593

  13. Surface segregation of fluorinated moieties on random copolymer films controlled by random-coil conformation of polymer chains in solution.

    PubMed

    Xue, Dongwu; Wang, Xinping; Ni, Huagang; Zhang, Wei; Xue, Gi

    2009-02-17

    The relationship between solution properties, film-forming methods, and the solid surface structures of random copolymers composed of butyl methacrylate and dodecafluorheptyl methylacrylate (DFHMA) was investigated by contact angle measurements, X-ray photoelectron spectroscopy, sum frequency generation vibrational spectroscopy, and surface tension measurements. The results, based on thermodynamic considerations, demonstrated that the random copolymer chain conformation at the solution/air interface greatly affected the surface structure of the resulting film, thereby determining the surface segregation of fluorinated moieties on films obtained by various film-forming techniques. When the fluorinated monomer content of the copolymer solution was low, entropic forces dominated the interfacial structure, with the perfluoroalkyl groups unable to migrate to the solution/air interface and thus becoming buried in a random-coil chain conformation. When employing this copolymer solution for film preparation by spin-coating, the copolymer chains in solution were likely extended due to centrifugal forces, thereby weakening the entropy effect of the polymer chains. Consequently, this resulted in the segregation of the fluorinated moieties on the film surface. For the films prepared by casting, the perfluoroalkyl groups were, similar to those in solution, incapable of segregating at the film surface and were thus buried in the random-coil chains. When the copolymers contained a high content of DFHMA, the migration of perfluoroalkyl groups at the solution/air interface was controlled by enthalpic forces, and the perfluoroalkyl groups segregated at the surface of the film regardless of the film-forming technique. The aim of the present work was to obtain an enhanced understanding of the formation mechanism of the chemical structure on the surface of the polymer film, while demonstrating that film-forming methods may be used in practice to promote the segregation of fluorinated

  14. Conformal Infinity

    NASA Astrophysics Data System (ADS)

    Frauendiener, Jörg

    2004-12-01

    The notion of conformal infinity has a long history within the research in Einstein's theory of gravity. Today, "conformal infinity" is related to almost all other branches of research in general relativity, from quantisation procedures to abstract mathematical issues to numerical applications. This review article attempts to show how this concept gradually and inevitably evolved from physical issues, namely the need to understand gravitational radiation and isolated systems within the theory of gravitation, and how it lends itself very naturally to the solution of radiation problems in numerical relativity. The fundamental concept of null-infinity is introduced. Friedrich's regular conformal field equations are presented and various initial value problems for them are discussed. Finally, it is shown that the conformal field equations provide a very powerful method within numerical relativity to study global problems such as gravitational wave propagation and detection.

  15. General Conformity

    EPA Pesticide Factsheets

    The General Conformity requirements ensure that the actions taken by federal agencies in nonattainment and maintenance areas do not interfere with a state’s plans to meet national standards for air quality.

  16. BET-Inhibitors Disrupt Rad21-Dependent Conformational Control of KSHV Latency

    PubMed Central

    Chen, Horng-Shen; De Leo, Alessandra; Kerekovic, Andrew; Hills, Robert

    2017-01-01

    Kaposi’s Sarcoma-associated Herpesvirus (KSHV) establishes stable latent infection in B-lymphocytes and pleural effusion lymphomas (PELs). During latency, the viral genome persists as an epigenetically constrained episome with restricted gene expression programs. To identify epigenetic regulators of KSHV latency, we screened a focused small molecule library containing known inhibitors of epigenetic factors. We identified JQ1, a Bromodomain and Extended Terminal (BET) protein inhibitor, as a potent activator of KSHV lytic reactivation from B-cells carrying episomal KSHV. We validated that JQ1 and other BET inhibitors efficiently stimulated reactivation of KSHV from latently infected PEL cells. We found that BET proteins BRD2 and BRD4 localize to several regions of the viral genome, including the LANA binding sites within the terminal repeats (TR), as well as at CTCF-cohesin sites in the latent and lytic control regions. JQ1 did not disrupt the interaction of BRD4 or BRD2 with LANA, but did reduce the binding of LANA with KSHV TR. We have previously demonstrated a cohesin-dependent DNA-loop interaction between the latent and lytic control regions that restrict expression of ORF50/RTA and ORF45 immediate early gene transcripts. JQ1 reduced binding of cohesin subunit Rad21 with the CTCF binding sites in the latency and lytic control regions. JQ1 also reduced DNA-loop interaction between latent and lytic control regions. These findings implicate BET proteins BRD2 and BRD4 in the maintenance of KSHV chromatin architecture during latency and reveal BET inhibitors as potent activators of KSHV reactivation from latency. PMID:28107481

  17. 5. FIRST FLOOR INTERIOR, NITROGEN MACHINERY, MACHINERY ROOM (SEE N4) ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. FIRST FLOOR INTERIOR, NITROGEN MACHINERY, MACHINERY ROOM (SEE N-4) FROM EASTERN ENTRANCE, LOOKING EAST. - Oakland Naval Supply Center, Cold Storage Warehouse, South of C Street between First & Second Street, Oakland, Alameda County, CA

  18. Accessorizing the human mitochondrial transcription machinery.

    PubMed

    Bestwick, Megan L; Shadel, Gerald S

    2013-06-01

    The human genome comprises large chromosomes in the nucleus and mitochondrial DNA (mtDNA) housed in the dynamic mitochondrial network. Human cells contain up to thousands of copies of the double-stranded, circular mtDNA molecule that encodes essential subunits of the oxidative phosphorylation complexes and the rRNAs and tRNAs needed to translate these in the organelle matrix. Transcription of human mtDNA is directed by a single-subunit RNA polymerase, POLRMT, which requires two primary transcription factors, TFB2M (transcription factor B2, mitochondrial) and TFAM (transcription factor A, mitochondrial), to achieve basal regulation of the system. Here, we review recent advances in understanding the structure and function of the primary human transcription machinery and the other factors that facilitate steps in transcription beyond initiation and provide more intricate control over the system. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Accessorizing the human mitochondrial transcription machinery

    PubMed Central

    Bestwick, Megan L.; Shadel, Gerald S.

    2013-01-01

    The human genome comprises large chromosomes in the nucleus and mitochondrial DNA (mtDNA) housed in the dynamic mitochondrial network. Human cells contain up to thousands of copies of the double-stranded, circular mtDNA molecule that encodes essential subunits of the oxidative phosphorylation complexes and the rRNAs and tRNAs needed to translate these in the organelle matrix. Transcription of human mtDNA is directed by a single-subunit RNA polymerase, POLRMT, which requires two primary transcription factors, TFB2M and TFAM, to achieve basal regulation of the system. Here we review recent advances in understanding the structure and function of the primary human transcription machinery and the other factors that facilitate steps in transcription beyond initiation and provide more intricate control over the system. PMID:23632312

  20. Cu nanocrystal growth on peptide nanotubes by biomineralization: Size control of Cu nanocrystals by tuning peptide conformation

    NASA Astrophysics Data System (ADS)

    Banerjee, Ipsita A.; Yu, Lingtao; Matsui, Hiroshi

    2003-12-01

    With recent interest in seeking new biologically inspired device-fabrication methods in nanotechnology, a new biological approach was examined to fabricate Cu nanotubes by using sequenced histidine-rich peptide nanotubes as templates. The sequenced histidine-rich peptide molecules were assembled as nanotubes, and the biological recognition of the specific sequence toward Cu lead to efficient Cu coating on the nanotubes. Cu nanocrystals were uniformly coated on the histidine-incorporated nanotubes with high packing density. In addition, the diameter of Cu nanocrystal was controlled between 10 and 30 nm on the nanotube by controlling the conformation of histidine-rich peptide by means of pH changes. Those nanotubes showed significant change in electronic structure by varying the nanocrystal diameter; therefore, this system may be developed to a conductivity-tunable building block for microelectronics and biological sensors. This simple biomineralization method can be applied to fabricate various metallic and semiconductor nanotubes with peptides whose sequences are known to mineralize specific ions.

  1. FOREWORD: 26th IAHR Symposium on Hydraulic Machinery and Systems

    NASA Astrophysics Data System (ADS)

    Wu, Yulin; Wang, Zhengwei; Liu, Shuhong; Yuan, Shouqi; Luo, Xingqi; Wang, Fujun

    2012-11-01

    was molded into a polytechnic institute focusing on engineering in the nationwide restructuring of universities and colleges undertaken in 1952. At present, the university has 14 schools and 56 departments with faculties in science, engineering, humanities, law, medicine, history, philosophy, economics, management, education and art. The University now has over 25 900 students, including 13 100 undergraduates and 12 800 graduate students. As one of China's most renowned universities, Tsinghua has become an important institution for fostering talents and scientific research. The International Association of Hydro-Environment Engineering and Research (IAHR) particularly promotes the advancement and exchange of knowledge through working groups, specialty symposia, congresses, and publications on water resources, river and coastal hydraulics, risk analysis, energy, environment, disaster prevention, and industrial processes. The IAHR Committee on Hydraulic Machinery and Systems deals with the advancement of technology associated with the understanding of steady and unsteady flow characteristics in hydraulic machinery and conduit systems connected to the machinery. The technology elements include the fluid behaviour within machine components, hydro-elastic behaviour of machine components, cavitation and two phase flow in turbines and pumps, hydraulic machine and plant control systems, the use of hydraulic machines to improve water quality, and even considerations to improve fish survival in their passage through hydro plants. The main emphases of the IAHR Committee on Hydraulic Machinery and Systems are to stimulate research and understanding of the technologies associated with hydraulic machinery and to promote interaction between the machine designers, machine users, the academic community, and the community as a whole. Hydraulic machinery is both cost effective and environmentally friendly. The goals of the IAHR Committee on Hydraulic Machinery and Systems are to improve

  2. Conformationally Constrained Histidines in the Design of Peptidomimetics: Strategies for the χ-Space Control

    PubMed Central

    Stefanucci, Azzurra; Pinnen, Francesco; Feliciani, Federica; Cacciatore, Ivana; Lucente, Gino; Mollica, Adriano

    2011-01-01

    A successful design of peptidomimetics must come to terms with χ-space control. The incorporation of χ-space constrained amino acids into bioactive peptides renders the χ1 and χ2 torsional angles of pharmacophore amino acids critical for activity and selectivity as with other relevant structural features of the template. This review describes histidine analogues characterized by replacement of native α and/or β-hydrogen atoms with alkyl substituents as well as analogues with α, β-didehydro unsaturation or Cα-Cβ cyclopropane insertion (ACC derivatives). Attention is also dedicated to the relevant field of β-aminoacid chemistry by describing the synthesis of β2- and β3-models (β-hHis). Structural modifications leading to cyclic imino derivatives such as spinacine, aza-histidine and analogues with shortening or elongation of the native side chain (nor-histidine and homo-histidine, respectively) are also described. Examples of the use of the described analogues to replace native histidine in bioactive peptides are also given. PMID:21686155

  3. Genetic variants in the microRNA machinery gene GEMIN4 are associated with risk of prostate cancer: a case-control study of the Chinese Han population.

    PubMed

    Liu, Jiaming; Liu, Jinnan; Wei, Mingtian; He, Yazhou; Liao, Banghua; Liao, Ga; Li, Hong; Huang, Jin

    2012-07-01

    Single-nucleotide polymorphisms located in the microRNA biogenesis pathway could alter the risk for developing prostate cancer. The present study was intended to identify common genetic variants responsible for prostate cancer susceptibility in the GEMIN4 gene. The high-resolution melting method was used to genotype seven polymorphisms (rs7813, rs4968104, rs3744741, rs2740348, rs1062923, rs910925, and rs910924) in the GEMIN4 gene in 300 prostate cancer patients and 244 matched controls. The encouraging discovery in this study was in the rs2740348. Patients carrying the variant heterozygote GC genotype in the rs2740348 were at a 36% decreased risk of prostate cancer (odds ratio [OR] = 0.64; 95% confidence interval [CI] = 0.42, 0.99). Similarly, this variant allele carrier showed significant risk for prostate cancer (OR = 0.64). In addition, subjects carrying the homozygote TT genotype in the rs7813 had a significantly increased risk of prostate cancer (OR = 2.53, 95% CI = 1.07, 6.28). Two common haplotypes were found to be associated with decreased risk of prostate cancer. In the subgroup analysis, higher risk of more severity of prostate cancer (clinical stage III and IV) was observed in individuals with the rs7813 TT genotype (OR = 2.64, 95% CI = 1.02, 7.64), while lower risk of more severity of prostate cancer was observed in individuals with the rs3744741 T allele (OR = 0.69, 95% CI = 0.50, 0.96). Overall, our study provides substantial support for the association between the GEMIN4 gene and the risk of prostate cancer.

  4. COMBINED MICROBIAL SURFACTANT-POLYMER SYSTEM FOR IMPROVED OIL MOBILITY AND CONFORMANCE CONTROL

    SciTech Connect

    Jorge Gabitto; Maria Barrufet

    2004-08-01

    Many domestic oil fields are facing abandonment even though they still contain two-thirds of their original oil. A significant number of these fields can yield additional oil using advanced oil recovery (AOR) technologies. To maintain domestic oil production at current levels, AOR technologies are needed that are affordable and can be implemented by independent oil producers of the future. Microbial enhanced oil recovery (MEOR) technologies have become established as cost-effective solutions for declining oil production. MEOR technologies are affordable for independent producers operating stripper wells and can be used to extend the life of marginal fields. The demonstrated versatility of microorganisms can be used to design advanced microbial systems to treat multiple production problems in complex, heterogeneous reservoirs. The proposed research presents the concept of a combined microbial surfactant-polymer system for advanced oil recovery. The surfactant-polymer system utilizes bacteria that are capable of both biosurfactant production and metabolically-controlled biopolymer production. This novel technology combines complementary mechanisms to extend the life of marginal fields and is applicable to a large number of domestic reservoirs. The research project described in this report is performed jointly by, Bio-Engineering Inc., a woman owned small business, Texas A&M University and Prairie View A&M University, a Historically Black College and University. This report describes the results of our laboratory work to grow microbial cultures and the work done on recovery experiments on core rocks. We have selected two bacterial strains capable of producing both surfactant and polymers. We have conducted laboratory experiments to determine under what conditions surfactants and polymers can be produced from one single strain. We have conduct recovery experiments to determine the performance of these strains under different conditions. Our results do not show a

  5. Binding Induced RNA Conformational Changes Control Substrate Recognition and Catalysis by the Thiostrepton Resistance Methyltransferase (Tsr)*

    PubMed Central

    Kuiper, Emily G.; Conn, Graeme L.

    2014-01-01

    Ribosomal RNA (rRNA) post-transcriptional modifications are essential for ribosome maturation, translational fidelity, and are one mechanism used by both antibiotic-producing and pathogenic bacteria to resist the effects of antibiotics that target the ribosome. The thiostrepton producer Streptomyces azureus prevents self-intoxication by expressing the thiostrepton-resistance methyltransferase (Tsr), which methylates the 2′-hydroxyl of 23 S rRNA nucleotide adenosine 1067 within the thiostrepton binding site. Tsr is a homodimer with each protomer containing an L30e-like amino-terminal domain (NTD) and a SPOUT methyltransferase family catalytic carboxyl-terminal domain (CTD). We show that both enzyme domains are required for high affinity RNA substrate binding. The Tsr-CTD has intrinsic, weak RNA affinity that is necessary to direct the specific high-affinity Tsr-RNA interaction via NTDs, which have no detectable RNA affinity in isolation. RNA structure probing experiments identify the Tsr footprint on the RNA and structural changes in the substrate, induced specifically upon NTD binding, which are necessary for catalysis by the CTD. Additionally, we identify a key amino acid in each domain responsible for CTD-RNA binding and the observed NTD-dependent RNA structural changes. These studies allow us to develop a model for Tsr-RNA interaction in which the coordinated substrate recognition of each Tsr structural domain is an obligatory pre-catalytic recognition event. Our findings underscore the complexity of substrate recognition by RNA modification enzymes and the potential for direct involvement of the RNA substrate in controlling the process of its modification. PMID:25086036

  6. Charge Pairing Interactions Control the Conformational Setpoint and Motions of the FMN Domain in Neuronal Nitric Oxide Synthase

    PubMed Central

    Haque, Mohammad Mahfuzul; Bayachou, Mekki; Fadlalla, Mohammed A.; Durra, Deborah; Stuehr, Dennis J.

    2013-01-01

    SYNOPSIS The Nitric Oxide Synthases (NOS; EC 1.14.13.39) contain a C-terminal flavoprotein domain (NOSred) that binds FAD and FMN and an N-terminal oxygenase domain that binds heme. Evidence suggests that the FMN-binding domain undergoes large conformational motions to shuttle electrons between the NADPH/FAD-binding domain (FNR) and the oxygenase domain. previously we showed that three residues on the FMN domain (Glu762, Glu816 and Glu819) that make charge-pairing interactions with the FNR help to slow electron flux through nNOSred. In this study, we show that charge neutralization or reversal at each of these residues alters the setpoint (KeqA) of the NOSred conformational equilibrium to favor of the open (FMN-deshielded) conformational state. Moreover, computer simulations of the kinetic traces of cytochrome c reduction by the mutants suggest that they have relatively larger effects on the conformational transition rates (from 1.5 to 4x faster) and the rate of interflavin electron transfer (from 1.5 to 2x faster) relative to wild type nNOSred. We conclude that the three charge-pairing residues on the FMN domain govern electron flux through nNOSred by stabilizing its closed (FMN-shielded) conformational state and by retarding the rate of conformational switching between its open and closed conformations. PMID:23289611

  7. 46 CFR 58.01-45 - Machinery space, ventilation.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 2 2014-10-01 2014-10-01 false Machinery space, ventilation. 58.01-45 Section 58.01-45... MACHINERY AND RELATED SYSTEMS General Requirements § 58.01-45 Machinery space, ventilation. Each machinery space must be ventilated to ensure that, when machinery or boilers are operating at full power in all...

  8. 46 CFR 58.01-45 - Machinery space, ventilation.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Machinery space, ventilation. 58.01-45 Section 58.01-45... MACHINERY AND RELATED SYSTEMS General Requirements § 58.01-45 Machinery space, ventilation. Each machinery space must be ventilated to ensure that, when machinery or boilers are operating at full power in all...

  9. 46 CFR 58.01-45 - Machinery space, ventilation.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 2 2012-10-01 2012-10-01 false Machinery space, ventilation. 58.01-45 Section 58.01-45... MACHINERY AND RELATED SYSTEMS General Requirements § 58.01-45 Machinery space, ventilation. Each machinery space must be ventilated to ensure that, when machinery or boilers are operating at full power in all...

  10. 46 CFR 58.01-45 - Machinery space, ventilation.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 2 2011-10-01 2011-10-01 false Machinery space, ventilation. 58.01-45 Section 58.01-45... MACHINERY AND RELATED SYSTEMS General Requirements § 58.01-45 Machinery space, ventilation. Each machinery space must be ventilated to ensure that, when machinery or boilers are operating at full power in...

  11. 46 CFR 58.01-45 - Machinery space, ventilation.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Machinery space, ventilation. 58.01-45 Section 58.01-45... MACHINERY AND RELATED SYSTEMS General Requirements § 58.01-45 Machinery space, ventilation. Each machinery space must be ventilated to ensure that, when machinery or boilers are operating at full power in...

  12. [Dosimetric evaluation of conformal radiotherapy: conformity factor].

    PubMed

    Oozeer, R; Chauvet, B; Garcia, R; Berger, C; Felix-Faure, C; Reboul, F

    2000-01-01

    The aim of three-dimensional conformal therapy (3DCRT) is to treat the Planning Target Volume (PTV) to the prescribed dose while reducing doses to normal tissues and critical structures, in order to increase local control and reduce toxicity. The evaluation tools used for optimizing treatment techniques are three-dimensional visualization of dose distributions, dose-volume histograms, tumor control probabilities (TCP) and normal tissue complication probabilities (NTCP). These tools, however, do not fully quantify the conformity of dose distributions to the PTV. Specific tools were introduced to measure this conformity for a given dose level. We have extended those definitions to different dose levels, using a conformity index (CI). CI is based on the relative volumes of PTV and outside the PTV receiving more than a given dose. This parameter has been evaluated by a clinical study including 82 patients treated for lung cancer and 82 patients treated for prostate cancer. The CI was low for lung dosimetric studies (0.35 at the prescribed dose 66 Gy) due to build-up around the GTV and to spinal cord sparing. For prostate dosimetric studies, the CI was higher (0.57 at the prescribed dose 70 Gy). The CI has been used to compare treatment plans for lung 3DCRT (2 vs 3 beams) and prostate 3DCRT (4 vs 7 beams). The variation of CI with dose can be used to optimize dose prescription.

  13. Conformation of dehydropentapeptides containing four achiral amino acid residues – controlling the role of L-valine

    PubMed Central

    Krzciuk-Gula, Joanna; Makowski, Maciej; Latajka, Rafał; Kafarski, Paweł

    2014-01-01

    Summary Structural studies of pentapeptides containing an achiral block, built from two dehydroamino acid residues (ΔZPhe and ΔAla) and two glycines, as well as one chiral L-Val residue were performed using NMR spectroscopy. The key role of the L-Val residue in the generation of the secondary structure of peptides is discussed. The obtained results suggest that the strongest influence on the conformation of peptides arises from a valine residue inserted at the C-terminal position. The most ordered conformation was found for peptide Boc-Gly-ΔAla-Gly-ΔZPhe-Val-OMe (3), which adopts a right-handed helical conformation. PMID:24778717

  14. Kinetic-dynamic model for conformational control of an electron transfer photocycle: mixed-metal hemoglobin hybrids.

    PubMed

    Patel, Ami D; Nocek, Judith M; Hoffman, Brian M

    2008-09-18

    It is becoming increasingly clear that the transfer of an electron across a protein-protein interface is coupled to the dynamics of conformational conversion between and within ensembles of interface conformations. Electron transfer (ET) reactions in conformationally mobile systems provide a "clock" against which the rapidity of a dynamic process may be measured, and we here report a simple kinetic (master equation) model that self-consistently incorporates conformational dynamics into an ET photocycle comprised of a photoinitiated "forward" step and thermal return to ground. This kinetic/dynamic (KD) model assumes an ET complex exists as multiple interconverting conformations which partition into an ET-optimized (reactive; R) population and a less-reactive population ( S). We take the members of each population to be equivalent by constraining them to have the same conformational energy, the same average rate constant for conversion to members of the other population, and the same rate constants for forward and back ET. The result is a mapping of a complicated energy surface onto the simple "gating", two-well surface, but with rate constants that are defined microscopically. This model successfully describes the changes in the ET photocycle within the "predocked" mixed-metal hemoglobin (Hb) hybrid, [alpha(Zn), beta(Fe3+N 3 (-))], as conformational kinetics are modulated by variations in viscosity (eta = 1-15 cP; 20 degrees C). The description reveals how the conformational "routes" by which a hybrid progresses through a photocycle differ in different dynamic regimes. Even at eta = 1 cP, the populations are not in fast exchange, and ET involves a complex interplay between conformational and ET processes; at intermediate viscosities the hybrid exhibits "differential dynamics" in which the forward and back ET processes involve different initial ensembles of configurational substates; by eta = 15 cP, the slow-exchange limit is approached. Even at low viscosity, the ET

  15. Saturation Mutagenesis of the HIV-1 Envelope CD4 Binding Loop Reveals Residues Controlling Distinct Trimer Conformations

    PubMed Central

    Bolon, Daniel; Clapham, Paul R.

    2016-01-01

    The conformation of HIV-1 envelope (Env) glycoprotein trimers is key in ensuring protection against waves of neutralizing antibodies generated during infection, while maintaining sufficient exposure of the CD4 binding site (CD4bs) for viral entry. The CD4 binding loop on Env is an early contact site for CD4 while penetration of a proximal cavity by CD4 triggers Env conformational changes for entry. The role of residues in the CD4 binding loop in regulating the conformation of the trimer and trimer association domain (TAD) was investigated using a novel saturation mutagenesis approach. Single mutations identified, resulted in distinct trimer conformations affecting CD4bs exposure, the glycan shield and the TAD across diverse HIV-1 clades. Importantly, mutations that improve access to the CD4bs without exposing the immunodominant V3 loop were identified. The different trimer conformations identified will affect the specificity and breadth of nabs elicited in vivo and are important to consider in design of Env immunogens for vaccines. PMID:27820858

  16. Productivity Growth Average in Farm Machinery Manufacturing.

    ERIC Educational Resources Information Center

    Herman, Arthur S.; Ferris, John W.

    1982-01-01

    Productivity in farm machinery manufacturing is examined. The authors discuss how the national economy affects productivity, how the growth of agriculture and technology has changed the industry, and how future trends may cause change in the industry. (CT)

  17. Use laser-optics for machinery alignment

    SciTech Connect

    Bloch, H.P.

    1987-10-01

    Many sources attribute most bearing overload and destructive vibration in industrial machinery to shaft misalignment. There is considerable disagreement as to the alignment quality required. There is also little agreement on suitable calculation methods and achievable accuracy for anticipated thermal growth of machinery (necessary if running alignment is to remain acceptable). This article examines existing alignment quality guidelines for relevance and consistency, and reviews the application of laser-optic alignment systems based on three years of field experience.

  18. Navigation of Construction and Agriculture Machinery

    NASA Astrophysics Data System (ADS)

    Stempfhuber, Werner

    2008-09-01

    Over the last two decades terrestrial and global 3D measurement sensors in the field of engineering geodesy have seen a significant upturn. With modern measurement techniques, a 3D trajectory of a moving object can be determined within a few centimetres (mostly with Global Navigation Satellite Systems, GNSS), under certain circumstances and with an overall understanding of the applied method accuracies of within 5 to 10 millimetres can be achieved (tracking total station). New application areas have been now created in the fields of construction, mining and agriculture. The guidance or control of heavy machinery demands a navigation sensor with an appropriate measurement rate and accuracy, as well as stable and reliable performance. The 3D position, together with the orientation as well as the long and cross inclination information is hereby just one part of the absolute machine guidance or control unit. Data collection, verification, management and interaction of the position information with the 6 degrees of freedom, together and the machine controller, are needed for the overall system. Rotation ring sensors for height control or height guidance are well-known amongst construction jobs and have been in use for more than 20 years. The first GPS-based guidance system for yield mapping was used 15 years ago (Auernhammer 1995). Optimization and improvements in efficiency are the principal reasons for the current developments in the area of 3D-based machine control and guidance. This paper will describe the state-of-the-art and general approaches as well as the real-time 3D measurement techniques in construction and agriculture environment.

  19. siRNA machinery in whitefly (Bemisia tabaci).

    PubMed

    Upadhyay, Santosh Kumar; Dixit, Sameer; Sharma, Shailesh; Singh, Harpal; Kumar, Jitesh; Verma, Praveen C; Chandrashekar, K

    2013-01-01

    RNA interference has been emerged as an utmost tool for the control of sap sucking insect pests. Systemic response is necessary to control them in field condition. Whitefly is observed to be more prone to siRNA in recent studies, however the siRNA machinery and mechanism is not well established. To identify the core siRNA machinery, we curated transcriptome data of whitefly from NCBI database. Partial mRNA sequences encoding Dicer2, R2D2, Argonaute2 and Sid1 were identified by tblastn search of homologous sequences from Aphis glycines and Tribolium castaneum. Complete encoding sequences were obtained by RACE, protein sequences derived by Expasy translate tool and confirmed by blastp analysis. Conserved domain search and Prosite-Scan showed similar domain architecture as reported in homologs from related insects. We found helicase, PAZ, RNaseIIIa, RNaseIIIb and double-stranded RNA-binding fold (DSRBF) in Dicer2; DsRBD in R2D2; and PAZ and PIWI domains in Argonaute2. Eleven transmembrane domains were detected in Sid1. Sequence homology and phylogenetic analysis revealed that RNAi machinery of whitefly is close to Aphids. Real-time PCR analysis showed similar expression of these genes in different developmental stages as reported in A. glycines and T. castaneum. Further, the expression level of above genes was quite similar to the housekeeping gene actin. Availability of core siRNA machinery including the Sid1 and their universal expression in reasonable quantity indicated significant response of whitefly towards siRNA. Present report opens the way for controlling whitefly, one of the most destructive crop insect pest.

  20. siRNA Machinery in Whitefly (Bemisia tabaci)

    PubMed Central

    Upadhyay, Santosh Kumar; Dixit, Sameer; Sharma, Shailesh; Singh, Harpal; Kumar, Jitesh; Verma, Praveen C.; Chandrashekar, K.

    2013-01-01

    Background RNA interference has been emerged as an utmost tool for the control of sap sucking insect pests. Systemic response is necessary to control them in field condition. Whitefly is observed to be more prone to siRNA in recent studies, however the siRNA machinery and mechanism is not well established. Methodology/Principal Findings To identify the core siRNA machinery, we curated transcriptome data of whitefly from NCBI database. Partial mRNA sequences encoding Dicer2, R2D2, Argonaute2 and Sid1 were identified by tblastn search of homologous sequences from Aphis glycines and Tribolium castaneum. Complete encoding sequences were obtained by RACE, protein sequences derived by Expasy translate tool and confirmed by blastp analysis. Conserved domain search and Prosite-Scan showed similar domain architecture as reported in homologs from related insects. We found helicase, PAZ, RNaseIIIa, RNaseIIIb and double-stranded RNA-binding fold (DSRBF) in Dicer2; DsRBD in R2D2; and PAZ and PIWI domains in Argonaute2. Eleven transmembrane domains were detected in Sid1. Sequence homology and phylogenetic analysis revealed that RNAi machinery of whitefly is close to Aphids. Real-time PCR analysis showed similar expression of these genes in different developmental stages as reported in A. glycines and T. castaneum. Further, the expression level of above genes was quite similar to the housekeeping gene actin. Conclusions/Significance Availability of core siRNA machinery including the Sid1 and their universal expression in reasonable quantity indicated significant response of whitefly towards siRNA. Present report opens the way for controlling whitefly, one of the most destructive crop insect pest. PMID:24391810

  1. Control of alcohol and drug use: changes to conform to new DOT transportation workplace testing procedures. Final rule.

    PubMed

    2001-08-09

    FRA is publishing a final rule conforming its drug and alcohol testing regulation to the December 19, 2000 revision of DOT's transportation workplace testing procedures. Consistency between the FRA's rule and DOT's revision is important in order to avoid overlap, conflict, duplication, or confusion among DOT drug and alcohol testing regulations.

  2. Structural analyses of human thymidylate synthase reveal a site that may control conformational switching between active and inactive states.

    PubMed

    Chen, Dan; Jansson, Anna; Sim, Daniel; Larsson, Andreas; Nordlund, Pär

    2017-08-11

    Thymidylate synthase (TS) is the sole enzyme responsible for de novo biosynthesis of thymidylate (TMP) and is essential for cell proliferation and survival. Inhibition of human TS (hTS) has been extensively investigated for cancer chemotherapy, but several aspects of its activity and regulation are still uncertain. In this study, we performed comprehensive structural and biophysical studies of hTS using crystallography and thermal shift assay and provided the first detailed structural information on the conformational changes induced by ligand binding to the hTS active site. We found that upon binding of the antifolate agents raltitrexed and nolatrexed, the two insert regions in hTS, the functions of which are unclear, undergo positional shifts toward the catalytic center. We investigated the inactive conformation of hTS and found that the two insert regions are also involved in the conformational transition between the active and inactive state of hTS. Moreover, we identified a ligand-binding site in the dimer interface, suggesting that the cavity in the dimer interface could serve as an allosteric site of hTS to regulate the conformational switching between the active and inactive states. On the basis of these findings, we propose a regulatory mechanism of hTS activity that involves allosteric regulation of interactions of hTS with its own mRNA depending on cellular demands for TMP. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Occupational Accidents with Agricultural Machinery in Austria.

    PubMed

    Kogler, Robert; Quendler, Elisabeth; Boxberger, Josef

    2016-01-01

    The number of recognized accidents with fatalities during agricultural and forestry work, despite better technology and coordinated prevention and trainings, is still very high in Austria. The accident scenarios in which people are injured are very different on farms. The common causes of accidents in agriculture and forestry are the loss of control of machine, means of transport or handling equipment, hand-held tool, and object or animal, followed by slipping, stumbling and falling, breakage, bursting, splitting, slipping, fall, and collapse of material agent. In the literature, a number of studies of general (machine- and animal-related accidents) and specific (machine-related accidents) agricultural and forestry accident situations can be found that refer to different databases. From the database Data of the Austrian Workers Compensation Board (AUVA) about occupational accidents with different agricultural machinery over the period 2008-2010 in Austria, main characteristics of the accident, the victim, and the employer as well as variables on causes and circumstances by frequency and contexts of parameters were statistically analyzed by employing the chi-square test and odds ratio. The aim of the study was to determine the information content and quality of the European Statistics on Accidents at Work (ESAW) variables to evaluate safety gaps and risks as well as the accidental man-machine interaction.

  4. 46 CFR 58.01-35 - Main propulsion auxiliary machinery.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 2 2012-10-01 2012-10-01 false Main propulsion auxiliary machinery. 58.01-35 Section 58... AUXILIARY MACHINERY AND RELATED SYSTEMS General Requirements § 58.01-35 Main propulsion auxiliary machinery. Auxiliary machinery vital to the main propulsion system must be provided in duplicate unless the...

  5. 46 CFR 58.01-35 - Main propulsion auxiliary machinery.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 2 2011-10-01 2011-10-01 false Main propulsion auxiliary machinery. 58.01-35 Section 58... AUXILIARY MACHINERY AND RELATED SYSTEMS General Requirements § 58.01-35 Main propulsion auxiliary machinery. Auxiliary machinery vital to the main propulsion system must be provided in duplicate unless the...

  6. 46 CFR 58.01-35 - Main propulsion auxiliary machinery.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Main propulsion auxiliary machinery. 58.01-35 Section 58... AUXILIARY MACHINERY AND RELATED SYSTEMS General Requirements § 58.01-35 Main propulsion auxiliary machinery. Auxiliary machinery vital to the main propulsion system must be provided in duplicate unless the...

  7. 46 CFR 58.01-35 - Main propulsion auxiliary machinery.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 2 2014-10-01 2014-10-01 false Main propulsion auxiliary machinery. 58.01-35 Section 58... AUXILIARY MACHINERY AND RELATED SYSTEMS General Requirements § 58.01-35 Main propulsion auxiliary machinery. Auxiliary machinery vital to the main propulsion system must be provided in duplicate unless the...

  8. 46 CFR 58.01-35 - Main propulsion auxiliary machinery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Main propulsion auxiliary machinery. 58.01-35 Section 58... AUXILIARY MACHINERY AND RELATED SYSTEMS General Requirements § 58.01-35 Main propulsion auxiliary machinery. Auxiliary machinery vital to the main propulsion system must be provided in duplicate unless the...

  9. 46 CFR 58.01-50 - Machinery space, noise.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 2 2014-10-01 2014-10-01 false Machinery space, noise. 58.01-50 Section 58.01-50... MACHINERY AND RELATED SYSTEMS General Requirements § 58.01-50 Machinery space, noise. (a) Each machinery space must be designed to minimize the exposure of personnel to noise in accordance with IMO A.468(XII...

  10. 46 CFR 42.15-35 - Machinery space openings.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 2 2014-10-01 2014-10-01 false Machinery space openings. 42.15-35 Section 42.15-35... BY SEA Conditions of Assignment of Freeboard § 42.15-35 Machinery space openings. (a) Machinery space..., funnel, or machinery space ventilators in an exposed position on the freeboard or superstructure deck...

  11. 46 CFR 174.195 - Bulkheads in machinery spaces.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Bulkheads in machinery spaces. 174.195 Section 174.195... in machinery spaces. (a) The bulkhead in each machinery space of each OSV must be watertight to the bulkhead deck. (b) Each penetration of, and each opening in, a bulkhead in a machinery space must— (1) Be...

  12. 46 CFR 45.149 - Machinery space openings.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Machinery space openings. 45.149 Section 45.149 Shipping... Assignment § 45.149 Machinery space openings. (a) Machinery space openings in position 1 or 2 must be framed... funnel or machinery space ventilator that must be kept open for the essential operations of the ship must...

  13. 46 CFR 45.149 - Machinery space openings.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 2 2012-10-01 2012-10-01 false Machinery space openings. 45.149 Section 45.149 Shipping... Assignment § 45.149 Machinery space openings. (a) Machinery space openings in position 1 or 2 must be framed... funnel or machinery space ventilator that must be kept open for the essential operations of the ship must...

  14. 46 CFR 45.149 - Machinery space openings.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 2 2014-10-01 2014-10-01 false Machinery space openings. 45.149 Section 45.149 Shipping... Assignment § 45.149 Machinery space openings. (a) Machinery space openings in position 1 or 2 must be framed... funnel or machinery space ventilator that must be kept open for the essential operations of the ship must...

  15. 46 CFR 174.195 - Bulkheads in machinery spaces.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Bulkheads in machinery spaces. 174.195 Section 174.195... in machinery spaces. (a) The bulkhead in each machinery space of each OSV must be watertight to the bulkhead deck. (b) Each penetration of, and each opening in, a bulkhead in a machinery space must— (1) Be...

  16. 46 CFR 42.15-35 - Machinery space openings.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Machinery space openings. 42.15-35 Section 42.15-35... BY SEA Conditions of Assignment of Freeboard § 42.15-35 Machinery space openings. (a) Machinery space..., funnel, or machinery space ventilators in an exposed position on the freeboard or superstructure deck...

  17. 46 CFR 42.15-35 - Machinery space openings.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 2 2012-10-01 2012-10-01 false Machinery space openings. 42.15-35 Section 42.15-35... BY SEA Conditions of Assignment of Freeboard § 42.15-35 Machinery space openings. (a) Machinery space..., funnel, or machinery space ventilators in an exposed position on the freeboard or superstructure deck...

  18. 46 CFR 174.195 - Bulkheads in machinery spaces.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Bulkheads in machinery spaces. 174.195 Section 174.195... in machinery spaces. (a) The bulkhead in each machinery space of each OSV must be watertight to the bulkhead deck. (b) Each penetration of, and each opening in, a bulkhead in a machinery space must— (1) Be...

  19. 46 CFR 58.01-50 - Machinery space, noise.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 2 2011-10-01 2011-10-01 false Machinery space, noise. 58.01-50 Section 58.01-50... MACHINERY AND RELATED SYSTEMS General Requirements § 58.01-50 Machinery space, noise. (a) Each machinery space must be designed to minimize the exposure of personnel to noise in accordance with IMO...

  20. 46 CFR 42.15-35 - Machinery space openings.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 2 2011-10-01 2011-10-01 false Machinery space openings. 42.15-35 Section 42.15-35... BY SEA Conditions of Assignment of Freeboard § 42.15-35 Machinery space openings. (a) Machinery space..., funnel, or machinery space ventilators in an exposed position on the freeboard or superstructure...

  1. 46 CFR 45.149 - Machinery space openings.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 2 2011-10-01 2011-10-01 false Machinery space openings. 45.149 Section 45.149 Shipping... Assignment § 45.149 Machinery space openings. (a) Machinery space openings in position 1 or 2 must be framed... funnel or machinery space ventilator that must be kept open for the essential operations of the ship...

  2. 46 CFR 42.15-35 - Machinery space openings.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Machinery space openings. 42.15-35 Section 42.15-35... BY SEA Conditions of Assignment of Freeboard § 42.15-35 Machinery space openings. (a) Machinery space..., funnel, or machinery space ventilators in an exposed position on the freeboard or superstructure...

  3. 46 CFR 45.149 - Machinery space openings.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Machinery space openings. 45.149 Section 45.149 Shipping... Assignment § 45.149 Machinery space openings. (a) Machinery space openings in position 1 or 2 must be framed... funnel or machinery space ventilator that must be kept open for the essential operations of the ship...

  4. 46 CFR 174.195 - Bulkheads in machinery spaces.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Bulkheads in machinery spaces. 174.195 Section 174.195... in machinery spaces. (a) The bulkhead in each machinery space of each OSV must be watertight to the bulkhead deck. (b) Each penetration of, and each opening in, a bulkhead in a machinery space must— (1)...

  5. 46 CFR 174.195 - Bulkheads in machinery spaces.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Bulkheads in machinery spaces. 174.195 Section 174.195... in machinery spaces. (a) The bulkhead in each machinery space of each OSV must be watertight to the bulkhead deck. (b) Each penetration of, and each opening in, a bulkhead in a machinery space must— (1)...

  6. 46 CFR 58.01-50 - Machinery space, noise.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Machinery space, noise. 58.01-50 Section 58.01-50... MACHINERY AND RELATED SYSTEMS General Requirements § 58.01-50 Machinery space, noise. (a) Each machinery space must be designed to minimize the exposure of personnel to noise in accordance with IMO...

  7. The retinoic acid machinery in invertebrates: ancestral elements and vertebrate innovations.

    PubMed

    Albalat, Ricard

    2009-12-10

    Recent discoveries have changed our view of the evolutionary history of retinoic acid (RA) machinery. It is no longer considered a vertebrate or chordate invention but rather a common genetic toolkit of diverse lineages of metazoans. In particular, the basic machinery of RA-metabolizing enzymes, retinoid-binding proteins and RA-binding nuclear receptors has been identified in protostome and deuterostome lineages. Moreover, the retinoid content and the effects of RA treatment have been described in a number of invertebrates, although the physiological role of RA signaling outside vertebrates is still not fully understood. This review summarizes the evidence gathered over many years on the invertebrate RA system, highlighting the ancient origin of the RA genetic machinery and a basic role in neuronal differentiation. Comparison of invertebrate and vertebrate RA toolkits suggests some innovations in the RA machinery of vertebrates that might have contributed to improving the physiological control of retinoid homeostasis, compensating for vitamin A fluctuations in this lineage. Analysis of the RA machinery in invertebrates also reveals independent losses of RA components during evolution, which might be related to changes in embryonic developmental modes and the absence of the temporal collinearity of hox clusters. Additional studies analyzing the biochemical and functional characteristics of the invertebrate RA genetic machinery are warranted to lend experimental support to the hypotheses sketched in this review. These hypotheses open, however, new perspectives toward understanding how the RA genetic machinery evolved to suit the physiological and developmental requirements of metazoans.

  8. The Ubiquitination, Disaggregation and Proteasomal Degradation Machineries in Polyglutamine Disease.

    PubMed

    Nath, Samir R; Lieberman, Andrew P

    2017-01-01

    Polyglutamine disorders are chronic, progressive neurodegenerative diseases caused by expansion of a glutamine tract in widely expressed genes. Despite excellent models of disease, a well-documented clinical history and progression, and established genetic causes, there are no FDA approved, disease modifying treatments for these disorders. Downstream of the mutant protein, several divergent pathways of toxicity have been identified over the last several decades, supporting the idea that targeting only one of these pathways of toxicity is unlikely to robustly alleviate disease progression. As a result, a vast body of research has focused on eliminating the mutant protein to broadly prevent downstream toxicity, either by silencing mutant protein expression or leveraging the endogenous protein quality control machinery. In the latter approach, a focus has been placed on four critical components of mutant protein degradation that are active in the nucleus, a key site of toxicity: disaggregation, ubiquitination, deubiquitination, and proteasomal activity. These machineries have unique functional components, but work together as a cellular defense system that can be successfully leveraged to alleviate disease phenotypes in several models of polyglutamine toxicity. This review will highlight recent advances in understanding both the potential and role of these components of the protein quality control machinery in polyglutamine disease pathophysiology.

  9. The Ubiquitination, Disaggregation and Proteasomal Degradation Machineries in Polyglutamine Disease

    PubMed Central

    Nath, Samir R.; Lieberman, Andrew P.

    2017-01-01

    Polyglutamine disorders are chronic, progressive neurodegenerative diseases caused by expansion of a glutamine tract in widely expressed genes. Despite excellent models of disease, a well-documented clinical history and progression, and established genetic causes, there are no FDA approved, disease modifying treatments for these disorders. Downstream of the mutant protein, several divergent pathways of toxicity have been identified over the last several decades, supporting the idea that targeting only one of these pathways of toxicity is unlikely to robustly alleviate disease progression. As a result, a vast body of research has focused on eliminating the mutant protein to broadly prevent downstream toxicity, either by silencing mutant protein expression or leveraging the endogenous protein quality control machinery. In the latter approach, a focus has been placed on four critical components of mutant protein degradation that are active in the nucleus, a key site of toxicity: disaggregation, ubiquitination, deubiquitination, and proteasomal activity. These machineries have unique functional components, but work together as a cellular defense system that can be successfully leveraged to alleviate disease phenotypes in several models of polyglutamine toxicity. This review will highlight recent advances in understanding both the potential and role of these components of the protein quality control machinery in polyglutamine disease pathophysiology. PMID:28381987

  10. ADJUSTMENT, MAINTENANCE, AND REPAIR OF CROP HARVESTING MACHINERY. AGRICULTURAL MACHINERY--SERVICE OCCUPATIONS, MODULE NUMBER 11.

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. Center for Vocational and Technical Education.

    ONE OF A SERIES DESIGNED FOR HELPING TEACHERS PREPARE POSTSECONDARY-LEVEL STUDENTS FOR AGRICULTURAL MACHINERY SERVICE OCCUPATIONS AS PARTS MEN, MECHANICS, MECHANIC'S HELPERS, AND SERVICE SUPERVISORS, THIS GUIDE AIMS TO DEVELOP STUDENT COMPETENCY IN ADJUSTING, REPAIRING, AND MAINTAINING CROP HARVESTING MACHINERY. SUGGESTIONS FOR INTRODUCTION OF THE…

  11. AGRICULTURAL MACHINERY ASSEMBLY AND LUBRICATION. AGRICULTURAL MACHINERY--SERVICE OCCUPATIONS, MODULE NUMBER 7.

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. Center for Vocational and Technical Education.

    ONE OF A SERIES DESIGNED TO HELP TEACHERS PREPARE POSTSECONDARY STUDENTS FOR THE AGRICULTURAL MACHINERY SERVICE OCCUPATIONS AS PARTS MEN, MECHANICS, MECHANIC'S HELPERS, AND SERVICE SUPERVISORS, THIS GUIDE AIMS TO DEVELOP STUDENT UNDERSTANDING OF THE FUNCTIONS OF LUBRICANTS FOR AGRICULTURAL MACHINERY, SKILL IN THEIR SELECTION, AND UNDERSTANDING OF…

  12. 40 CFR Appendix A to Part 438 - Typical Products in Metal Products and Machinery Sectors

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Components Mining machinery & equipment, except oil field MOTOR VEHICLE Auto Exhaust System Repair Shops... Machinery Motors & Generators Oil Field Machinery & Equipment Packaging Machinery Paper Industries Machinery... Airports, Flying Fields, & Services BUS & TRUCK Bus Terminal & Service Facilities Courier Services, Except...

  13. 40 CFR Appendix A to Part 438 - Typical Products in Metal Products and Machinery Sectors

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Components Mining machinery & equipment, except oil field MOTOR VEHICLE Auto Exhaust System Repair Shops... Machinery Motors & Generators Oil Field Machinery & Equipment Packaging Machinery Paper Industries Machinery... Airports, Flying Fields, & Services BUS & TRUCK Bus Terminal & Service Facilities Courier Services, Except...

  14. 40 CFR Appendix A to Part 438 - Typical Products in Metal Products and Machinery Sectors

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Components Mining machinery & equipment, except oil field MOTOR VEHICLE Auto Exhaust System Repair Shops... Machinery Motors & Generators Oil Field Machinery & Equipment Packaging Machinery Paper Industries Machinery... Airports, Flying Fields, & Services BUS & TRUCK Bus Terminal & Service Facilities Courier Services, Except...

  15. 40 CFR Appendix A to Part 438 - Typical Products in Metal Products and Machinery Sectors

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Components Mining machinery & equipment, except oil field MOTOR VEHICLE Auto Exhaust System Repair Shops... Machinery Motors & Generators Oil Field Machinery & Equipment Packaging Machinery Paper Industries Machinery... Fields, & Services BUS & TRUCK Bus Terminal & Service Facilities Courier Services, Except by Air Freight...

  16. An allosteric photoredox catalyst inspired by photosynthetic machinery

    PubMed Central

    Lifschitz, Alejo M.; Young, Ryan M.; Mendez-Arroyo, Jose; Stern, Charlotte L.; McGuirk, C. Michael; Wasielewski, Michael R.; Mirkin, Chad A.

    2015-01-01

    Biological photosynthetic machinery allosterically regulate light harvesting via conformational and electronic changes at the antenna protein complexes as a response to specific chemical inputs. Fundamental limitations in current approaches to regulating inorganic light-harvesting mimics prevent their use in catalysis. Here we show that a light-harvesting antenna/reaction centre mimic can be regulated by utilizing a coordination framework incorporating antenna hemilabile ligands and assembled via a high-yielding, modular approach. As in nature, allosteric regulation is afforded by coupling the conformational changes to the disruptions in the electrochemical landscape of the framework upon recognition of specific coordinating analytes. The hemilabile ligands enable switching using remarkably mild and redox-inactive inputs, allowing one to regulate the photoredox catalytic activity of the photosynthetic mimic reversibly and in situ. Thus, we demonstrate that bioinspired regulatory mechanisms can be applied to inorganic light-harvesting arrays displaying switchable catalytic properties and with potential uses in solar energy conversion and photonic devices. PMID:25817586

  17. Cancer gene therapy targeting cellular apoptosis machinery.

    PubMed

    Jia, Lin-Tao; Chen, Si-Yi; Yang, An-Gang

    2012-11-01

    The unraveling of cellular apoptosis machinery provides novel targets for cancer treatment, and gene therapy targeting this suicidal system has been corroborated to cause inflammation-free autonomous elimination of neoplastic cells. The apoptotic machinery can be targeted by introduction of a gene encoding an inducer, mediator or executioner of apoptotic cell death or by inhibition of anti-apoptotic gene expression. Strategies targeting cancer cells, which are achieved by selective gene delivery, specific gene expression or secretion of target proteins via genetic modification of autologous cells, dictate the outcome of apoptosis-based cancer gene therapy. Despite so far limited clinical success, gene therapy targeting the apoptotic machinery has great potential to benefit patients with threatening malignancies provided the availability of efficient and specific gene delivery and administration systems.

  18. The machinery of mitochondrial inheritance and behavior.

    PubMed

    Yaffe, M P

    1999-03-05

    The distribution of mitochondria to daughter cells during cell division is an essential feature of cell proliferation. Until recently, it was commonly believed that inheritance of mitochondria and other organelles was a passive process, a consequence of their random diffusion throughout the cytoplasm. A growing recognition of the reticular morphology of mitochondria in many living cells, the association of mitochondria with the cytoskeleton, and the coordinated movements of mitochondria during cellular division and differentiation has illuminated the necessity for a cellular machinery that mediates mitochondrial behavior. Characterization of the underlying molecular components of this machinery is providing insight into mechanisms regulating mitochondrial morphology and distribution.

  19. Rapid and conformal coating of polymer resins by airbrushing for continuous and high-speed roll-to-roll nanopatterning: parametric quality controls and extended applications

    NASA Astrophysics Data System (ADS)

    Lee, Jae Hyuk; Na, Minho; Kim, Jiyeop; Yoo, Kangeun; Park, Jaekyu; Kim, Jeong Dae; Oh, Dong Kyo; Lee, Seungjo; Youn, Hongseok; Kwak, Moon Kyu; Ok, Jong G.

    2017-05-01

    We present a facile and scalable coating method based on controlled airbrushing, which is suitable for conformal resin coating in continuous roll-to-roll (R2R) nanoimprint lithography (NIL) process. By controlling the concentration of UV-curable polymeric resin with mixing the volatile solvent and its airbrushing time, the coated resin film thickness can be readily tuned. After R2R NIL using a flexible nanoscale line pattern (nanograting) mold is conducted upon the airbrushed resin film, a large-area uniform nanograting pattern is fabricated with controlled residual layer thickness (RLT) based on the initial film thickness. We investigate the faithful airbrushing condition that can reliably create the uniform thin films as well as various nanopatterns with controlled morphologies. Using more diluted resin and shorter airbrushing time can reduce the RLTs favourably for many applications, yet is apt to induce the nanoscale pores and discontinued lines. We also discuss how to further improve the quality and scalability of resin airbrushing and its potential applications particularly requiring high-speed and conformal coating on highly topographic and flexible surfaces.

  20. Rapid and conformal coating of polymer resins by airbrushing for continuous and high-speed roll-to-roll nanopatterning: parametric quality controls and extended applications.

    PubMed

    Lee, Jae Hyuk; Na, Minho; Kim, Jiyeop; Yoo, Kangeun; Park, Jaekyu; Kim, Jeong Dae; Oh, Dong Kyo; Lee, Seungjo; Youn, Hongseok; Kwak, Moon Kyu; Ok, Jong G

    2017-01-01

    We present a facile and scalable coating method based on controlled airbrushing, which is suitable for conformal resin coating in continuous roll-to-roll (R2R) nanoimprint lithography (NIL) process. By controlling the concentration of UV-curable polymeric resin with mixing the volatile solvent and its airbrushing time, the coated resin film thickness can be readily tuned. After R2R NIL using a flexible nanoscale line pattern (nanograting) mold is conducted upon the airbrushed resin film, a large-area uniform nanograting pattern is fabricated with controlled residual layer thickness (RLT) based on the initial film thickness. We investigate the faithful airbrushing condition that can reliably create the uniform thin films as well as various nanopatterns with controlled morphologies. Using more diluted resin and shorter airbrushing time can reduce the RLTs favourably for many applications, yet is apt to induce the nanoscale pores and discontinued lines. We also discuss how to further improve the quality and scalability of resin airbrushing and its potential applications particularly requiring high-speed and conformal coating on highly topographic and flexible surfaces.

  1. 46 CFR 176.804 - Machinery.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... watertight bulkhead pipe penetration valves; (h) Operational test of the means provided for pumping bilges... certification of a vessel, the owner or managing operator shall be prepared to conduct tests and have the vessel... the main propulsion machinery both ahead and astern; (b) Operational test and inspection of...

  2. 46 CFR 176.804 - Machinery.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... watertight bulkhead pipe penetration valves; (h) Operational test of the means provided for pumping bilges... certification of a vessel, the owner or managing operator shall be prepared to conduct tests and have the vessel... the main propulsion machinery both ahead and astern; (b) Operational test and inspection of...

  3. 46 CFR 176.804 - Machinery.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... watertight bulkhead pipe penetration valves; (h) Operational test of the means provided for pumping bilges... certification of a vessel, the owner or managing operator shall be prepared to conduct tests and have the vessel... the main propulsion machinery both ahead and astern; (b) Operational test and inspection of...

  4. AGRICULTURAL MACHINERY--POWER. TEACHERS COPY.

    ERIC Educational Resources Information Center

    HILL, DURWIN; VENABLE, BENNY MAC

    THE PURPOSE OF THIS DOCUMENT IS TO PROVIDE A STUDY GUIDE FOR STUDENTS PREPARING FOR AGRICULTURAL MACHINERY OCCUPATIONS IN A VOCATIONAL AGRICULTURE COOPERATIVE EDUCATION PROGRAM. THE MATERIAL WAS DESIGNED BY SUBJECT MATTER SPECIALISTS ON THE BASIS OF STATE ADVISORY COMMITTEE RECOMMENDATIONS, TRIED IN OPERATIONAL PROGRAMS, AND REFINED BY A TEACHER.…

  5. 46 CFR 176.804 - Machinery.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... watertight bulkhead pipe penetration valves; (h) Operational test of the means provided for pumping bilges... certification of a vessel, the owner or managing operator shall be prepared to conduct tests and have the vessel... the main propulsion machinery both ahead and astern; (b) Operational test and inspection of...

  6. EARNINGS IN THE MACHINERY INDUSTRIES, MID-1966.

    ERIC Educational Resources Information Center

    BAUER, FREDERICK L.

    RESULTS OF A MID-1966 NATIONWIDE SURVEY BY THE BUREAU OF LABOR STATISTICS SHOWED THAT THE EARNINGS OF PRODUCTION AND RELATED NONELECTRICAL MACHINERY WORKERS IN 21 LARGE OCCUPATIONAL AREAS VARIED BY OCCUPATION, SIZE OF ESTABLISHMENT, AND COMMUNITY, INDUSTRY, LABOR-MANAGEMENT CONTRACT STATUS, AND LOCATION. THE AVERAGE HOURLY WAGE WAS $2.84. HIGHER…

  7. Equivalent Biochemical Control and Improved Prostate-Specific Antigen Nadir After Permanent Prostate Seed Implant Brachytherapy Versus High-Dose Three-Dimensional Conformal Radiotherapy and High-Dose Conformal Proton Beam Radiotherapy Boost

    SciTech Connect

    Jabbari, Siavash; Weinberg, Vivian K.; Shinohara, Katsuto; Speight, Joycelyn L.; Gottschalk, Alexander R.; Hsu, I.-C.; Pickett, Barby; McLaughlin, Patrick W.; Sandler, Howard M.; Roach, Mack

    2010-01-15

    Purpose: Permanent prostate implant brachytherapy (PPI), three-dimensional conformal radiotherapy (3D-CRT), and conformal proton beam radiotherapy (CPBRT) are used in the treatment of localized prostate cancer, although no head-to-head trials have compared these modalities. We studied the biochemical control (biochemical no evidence of disease [bNED]) and prostate-specific antigen (PSA) nadir achieved with contemporary PPI, and evaluated it against 3D-CRT and CPBRT. Patients and Methods: A total of 249 patients were treated with PPI at the University of California, San Francisco, and the outcomes were compared with those from a 3D-CRT cohort and the published results of a high-dose CPBRT boost (CPBRTB) trial. For each comparison, subsets of the PPI cohort were selected with patient and disease criteria similar to those of the reference group. Results: With a median follow-up of 5.3 years, the bNED rate at 5 and 7 years achieved with PPI was 92% and 86%, respectively, using the American Society for Therapeutic Radiology and Oncology (ASTRO) definition, and 93% using the PSA nadir plus 2 ng/mL definition. Using the ASTRO definition, a 5-year bNED rate of 78% was achieved for the 3D-CRT patients compared with 94% for a comparable PPI subset and 93% vs. 92%, respectively, using the PSA nadir plus 2 ng/mL definition. The median PSA nadir for patients treated with PPI and 3D-CRT was 0.10 and 0.40 ng/mL, respectively (p < .0001). For the CPBRT comparison, the 5-year bNED rate after a CPBRTB was 91% using the ASTRO definition vs. 93% for a similar group of PPI patients. A greater proportion of PPI patients achieved a lower PSA nadir compared with those achieved in the CPBRTB trial (PSA nadir <=0.5 ng/mL, 91% vs. 59%, respectively). Conclusion: We have demonstrated excellent outcomes in low- to intermediate-risk patients treated with PPI, suggesting at least equivalent 5-year bNED rates and a greater proportion of men achieving lower PSA nadirs compared with 3D-CRT or

  8. Operational safety practices as determinants of machinery-related injury on Saskatchewan farms.

    PubMed

    Narasimhan, Gopinath R; Peng, Yingwei; Crowe, Trever G; Hagel, Louise; Dosman, James; Pickett, William

    2010-07-01

    Agricultural machinery is a major source of injury on farms. The importance of machinery safety practices as potential determinants of injury remains incompletely understood. We examined two such safety practices as risk factors for injury: (1) the presence of safety devices on machinery and (2) low levels of routine machinery maintenance. Our data source was the Saskatchewan Farm Injury Cohort baseline survey (n=2390 farms). Factor analysis was used to create measures of the two operational safety practices. The farm was the unit for all analyses and associations were evaluated using multiple Poisson regression models. Limited presence of safety devices on machinery during farm operations was associated with higher risks for injury (RR 1.94; 95% CI 1.13-3.33; p(trend)=0.02). Lower routine maintenance scores were associated with significantly reduced risks for injury (RR 0.54; 95% CI 0.29-0.98; p(trend)=0.05). The first finding implies that injury prevention programs require continued focus on the use of safety devices on machinery. The second finding could indicate that maintenance itself is a risk factor or that more modern equipment that requires less maintenance places the operator at lower risk. These findings provide etiological data that confirms the practical importance of operational safety practices as components of injury control strategies on farms. Copyright 2010 Elsevier Ltd. All rights reserved.

  9. Predicting conformational switches in proteins.

    PubMed Central

    Young, M.; Kirshenbaum, K.; Dill, K. A.; Highsmith, S.

    1999-01-01

    We describe a new computational technique to predict conformationally switching elements in proteins from their amino acid sequences. The method, called ASP (Ambivalent Structure Predictor), analyzes results from a secondary structure prediction algorithm to identify regions of conformational ambivalence. ASP identifies ambivalent regions in 16 test protein sequences for which function involves substantial backbone rearrangements. In the test set, all sites previously described as conformational switches are correctly predicted to be structurally ambivalent regions. No such regions are predicted in three negative control protein sequences. ASP may be useful as a guide for experimental studies on protein function and motion in the absence of detailed three-dimensional structural data. PMID:10493576

  10. Conformation-controlled sorption properties and breathing of the aliphatic Al-MOF [Al(OH)(CDC)].

    PubMed

    Niekiel, Felicitas; Lannoeye, Jeroen; Reinsch, Helge; Munn, Alexis S; Heerwig, Andreas; Zizak, Ivo; Kaskel, Stefan; Walton, Richard I; de Vos, Dirk; Llewellyn, Philip; Lieb, Alexandra; Maurin, Guillaume; Stock, Norbert

    2014-05-05

    The Al-MOF CAU-13 ([Al(OH)(trans-CDC)]; trans-H2CDC = trans-1,4-cyclohexanedicarboxylic acid) is structurally related to the MIL-53 compounds that are well-known for their "breathing" behavior, i.e., the framework flexibility upon external stimuli such as the presence of adsorbate molecules. The adsorption properties of CAU-13 were investigated in detail. The sorption isotherms of N2, H2, CH4, CO, CO2, and water were recorded, and the adsorption enthalpies for the gases were determined by microcalorimetry. The structural changes upon adsorption of CO2 were followed with in situ synchrotron powder X-ray diffraction (PXRD). The patterns were analyzed by parametric unit cell refinement, and the preferential arrangement of the CO2 molecules was modeled by density functional theory calculations. The adsorption and separation of mixtures of o-, m-, and p-xylene from mesitylene showed a preferred adsorption of o-xylene. The structures of o/m/p-xylene-loaded CAU-13 were determined from PXRD data. The adsorption of xylene isomers induces a larger pore opening than that in the thermal activation of CAU-13. In the crystal structure of the activated sample CAU-13(empty pore), half of the linkers adopt the a,a confirmation and the other half the e,e conformation, and the presence of a,a-CDC(2-) ions hampers the structural flexibility of CAU-13. However, after the adsorption of xylene, all linkers are present in the e,e conformation, allowing for a wider pore opening by this new type of "breathing".

  11. New insights into the machinery of blood digestion by ticks.

    PubMed

    Sojka, Daniel; Franta, Zdeněk; Horn, Martin; Caffrey, Conor R; Mareš, Michael; Kopáček, Petr

    2013-06-01

    Blood-protein digestion is a key physiological process providing essential nutrients for ticks and is a prerequisite for the transmission of tick-borne pathogens. Recently, substantial progress has been made in determining the proteolytic machinery in tick gut tissue, which is based on a dynamic multienzyme network capable of processing a vast amount of host blood. In this article we summarize our current knowledge of the molecular mechanisms of tick hematophagy and their similarities to those of Platyhelminthes, nematodes, and Plasmodium. Future research perspectives, including the potential for rational control of ticks and transmitted diseases, are also discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Conformal ALON® windows

    NASA Astrophysics Data System (ADS)

    Goldman, Lee M.; Balasubramanian, Sreeram; Smith, Mark; Nag, Nagendra; Foti, Robyn; Jha, Santosh; Sastri, Suri

    2014-05-01

    Aluminum Oxynitride (ALON® Optical Ceramic) combines broadband transparency with excellent mechanical properties. ALON's cubic structure means that it is transparent in its polycrystalline form, allowing it to be manufactured by conventional powder processing techniques. Surmet controls every aspect of the manufacturing process, beginning with synthesis of ALON® powder, continuing through forming/heat treatment of blanks, ending with optical fabrication of ALON® windows. Surmet has made significant progress in its production capability in recent years. Additional scale up of Surmet's manufacturing capability, for complex geometries, larger sizes and higher quantities, is underway. The requirements for modern aircraft are driving the need for conformal windows for future sensor systems. However, limitations on optical systems and the ability to produce windows in complex geometries currently limit the geometry of existing windows and window assemblies to faceted assemblies of flat windows. Surmet's ability to produce large curved ALON® blanks is an important step in the development of conformal windows for future aircraft applications.

  13. 46 CFR 58.01-40 - Machinery, angles of inclination.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... AUXILIARY MACHINERY AND RELATED SYSTEMS General Requirements § 58.01-40 Machinery, angles of inclination. (a... angle of list up to and including 15°, and when the vessel is inclined under dynamic conditions (rolling...

  14. 46 CFR 58.01-40 - Machinery, angles of inclination.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... AUXILIARY MACHINERY AND RELATED SYSTEMS General Requirements § 58.01-40 Machinery, angles of inclination. (a... angle of list up to and including 15°, and when the vessel is inclined under dynamic conditions (rolling...

  15. 54. West emergency brake in the south machinery room (interior ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    54. West emergency brake in the south machinery room (interior of both machinery rooms is identical). Facing west. - Henry Ford Bridge, Spanning Cerritos Channel, Los Angeles-Long Beach Harbor, Los Angeles, Los Angeles County, CA

  16. 46 CFR 58.20-15 - Installation of refrigerating machinery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... AND AUXILIARY MACHINERY AND RELATED SYSTEMS Refrigeration Machinery § 58.20-15 Installation of... refrigeration compressor spaces shall be effectively ventilated and drained and shall be separated from...

  17. 46 CFR 58.20-15 - Installation of refrigerating machinery.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... AND AUXILIARY MACHINERY AND RELATED SYSTEMS Refrigeration Machinery § 58.20-15 Installation of... refrigeration compressor spaces shall be effectively ventilated and drained and shall be separated from...

  18. 52. Detail of electrical contacts in the south machinery room ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    52. Detail of electrical contacts in the south machinery room (interior of both machinery rooms is identical). Facing south. - Henry Ford Bridge, Spanning Cerritos Channel, Los Angeles-Long Beach Harbor, Los Angeles, Los Angeles County, CA

  19. 4. MACHINERY SHED AND STORAGE ROOM ADDITION, SOUTH AND WEST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. MACHINERY SHED AND STORAGE ROOM ADDITION, SOUTH AND WEST WALL LOOKING NORTHEAST SEED STORAGE BUILDING (1963) BEHIND - Tucson Plant Material Center, Machinery Shed, 3241 North Romero Road, Tucson, Pima County, AZ

  20. 51. Electrical contacts and relays in the south machinery room ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    51. Electrical contacts and relays in the south machinery room (interior of both machinery rooms is identical). Facing south. - Henry Ford Bridge, Spanning Cerritos Channel, Los Angeles-Long Beach Harbor, Los Angeles, Los Angeles County, CA

  1. Conformation and conformational exchange of Olopatadine hydrochloride

    NASA Astrophysics Data System (ADS)

    Lei, Lian-di; Zhu, Chuan-jun; Yang, Chun-hui; Cui, Yu-xin

    2008-12-01

    Besides the assignments of the 13C and 1H shifts by 1D and 2D NMR, the experiment 1H spectra of Olopatadine hydrochloride were recorded at temperature range 228-338 K. The variable-temperature spectra revealed a dynamic NMR effect which is attributed to conformational interconversion of the drug. At low temperature, the solution was shown to contain two conformers and the ration of them was 1:1. A conformational process with a free energy of activation of 56.7 kJ mol -1, coalescence temperature 298 K, was interpreted as geminal 1H exchange. Using molecule simulation, conformational candidates for two conformers are proposed.

  2. Violet-to-blue tunable emission of aryl-substituted dispirofluorene-indenofluorene isomers by conformationally-controllable intramolecular excimer formation.

    PubMed

    Thirion, Damien; Poriel, Cyril; Métivier, Rémi; Rault-Berthelot, Joëlle; Barrière, Frédéric; Jeannin, Olivier

    2011-09-05

    Two series of DiSpiroFluorene-IndenoFluorene (DSF-IF) positional isomers, namely dispiro[2,7-diarylfluorene-9',6,9'',12-indeno[1,2-b]fluorenes], (1,2-b)-DSF-IFs 1 and dispiro[2,7-diarylfluorene-9',6,9'',12-indeno[2,1-a]fluorenes], (2,1-a)-DSF-IFs 2 have been synthesized. These violet-to-blue fluorescent emitters possess a 3π-2spiro architecture, which combines via two spiro links two different indenofluorene cores, that is, (1,2-b)-IF or (2,1-a)-IF and 2,7-substituted-diaryl-fluorene units. Due to their different geometric profiles, the two families of positional isomers present drastically different properties. The marked difference observed between the properties of (1,2-b)-DSF-IF (1) and (2,1-a)-DSF-IF (2) is discussed in terms of intramolecular π-π interactions occurring in (2,1-a)-DSF-IF (2) leading to conformationally-controllable intramolecular excimer formation. Indeed, the original geometry of the (2,1-a)-DSF-IF (2) family, with face-to-face "aryl-fluorene-aryl" moieties, leads to remarkable excimer emission through intramolecular π-π interactions in the excited state. Furthermore, the emission wavelengths can be gradually modulated by the control of the steric hindrance between the adjacent substituted phenyl rings. Thus, through a comparative and detailed study of the (1)H NMR, electrochemical and photophysical properties of DSF-IFs 1 and 2, we have evidenced the intramolecular π-π interactions occurring between the two "aryl-fluorene-aryl" moieties in the ground state and in the excited state. These properties have been finally correlated to the spectacular conformational change modeled by density functional theory (DFT) calculations. Indeed, the two "aryl-fluorene-aryl" moieties switch from a staggered conformation in the ground state to an eclipsed conformation in the first excited state. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Fractionated Conformal Radiotherapy in the Management of Cavernous Sinus Meningiomas: Long-Term Functional Outcome and Tumor Control at a Single Institution

    SciTech Connect

    Metellus, Philippe; Batra, Sachin; Karkar, Siddharth; Kapoor, Sumit; Weiss, Stephanie; Kleinberg, Lawrence; Rigamonti, Danielle

    2010-11-01

    Purpose: To evaluate long-term outcome of cavernous sinus meningioma (CSM) treated with fractionated conformal radiotherapy (FCR). Patients and Methods: Fifty-three patients with CSMs (16 men [30.2%], 37 women [69.8%], aged 53 {+-} 13.0 years [mean {+-} SD]) were treated by FCR. In 28 patients (52.8%) FCR was performed as first-line treatment and in 25 patients (47.2%) as adjuvant treatment. All patients received FCR with a dose of 52.9 {+-} 1.8 Gy in 29.4 {+-} 1.0 fractions over 6 weeks. Dose per fraction was 1.9 {+-} 0.1 Gy. Radiotherapy was delivered stereotactically in 47 cases (88.7%) and conformally in 6 (11.3%) Results: The median follow-up was 6.9 years (range, 3-19 years). According to Sekhar's classification, 19 patients (35.8%) were Grade 1-2, 30 patients (56.6%) were Grade 3-4, and 4 patients (7.6%) were Grade 5. Pretreatment tumor volume was determined in 46 patients, and tumor volume was 12.6 {+-} 8.2 cm{sup 3}. In these patients, the distance between tumor and optic apparatus was 1.62 {+-} 1.2 mm. Actuarial 5- and 10-year progression-free survival rates were 98.1% and 95.8%, respectively. Clinical improvement was observed in 31 patients (58.5%), and 20 patients (37.7%) remained unchanged. Radiologic response was observed in 18 patients (30.2%), and 35 patients (66.0%) showed stable lesions. Two patients (3.8%) showed tumor progression during follow-up. Transient morbidity was observed in 3 patients (5.7%) and permanent morbidity in 1 (1.9%). Conclusion: Fractionated conformal radiotherapy affords satisfactory long-term tumor control and low treatment morbidity.

  4. 29 CFR 1910.214 - Cooperage machinery. [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 5 2014-07-01 2014-07-01 false Cooperage machinery. 1910.214 Section 1910.214 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR OCCUPATIONAL SAFETY AND HEALTH STANDARDS Machinery and Machine Guarding § 1910.214 Cooperage machinery....

  5. 46 CFR 58.01-25 - Means of stopping machinery.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... MACHINERY AND RELATED SYSTEMS General Requirements § 58.01-25 Means of stopping machinery. Machinery driving forced-draft and induced-draft fans, fuel-oil transfer pumps, fuel-oil unit and service pumps, and... space concerned so that the fans or pumps may be stopped in case of fire in the compartment in which...

  6. 29 CFR 1915.165 - Ship's deck machinery.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 7 2010-07-01 2010-07-01 false Ship's deck machinery. 1915.165 Section 1915.165 Labor... (CONTINUED) OCCUPATIONAL SAFETY AND HEALTH STANDARDS FOR SHIPYARD EMPLOYMENT Ship's Machinery and Piping Systems § 1915.165 Ship's deck machinery. (a) Before work is performed on the anchor windlass or any of...

  7. 29 CFR 1915.165 - Ship's deck machinery.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 7 2014-07-01 2014-07-01 false Ship's deck machinery. 1915.165 Section 1915.165 Labor... (CONTINUED) OCCUPATIONAL SAFETY AND HEALTH STANDARDS FOR SHIPYARD EMPLOYMENT Ship's Machinery and Piping Systems § 1915.165 Ship's deck machinery. (a) Before work is performed on the anchor windlass or any of...

  8. 46 CFR 185.352 - Ventilation of gasoline machinery spaces.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Ventilation of gasoline machinery spaces. 185.352... (UNDER 100 GROSS TONS) OPERATIONS Miscellaneous Operating Requirements § 185.352 Ventilation of gasoline machinery spaces. The mechanical exhaust for the ventilation of a gasoline machinery space, required by...

  9. 46 CFR 185.352 - Ventilation of gasoline machinery spaces.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Ventilation of gasoline machinery spaces. 185.352... (UNDER 100 GROSS TONS) OPERATIONS Miscellaneous Operating Requirements § 185.352 Ventilation of gasoline machinery spaces. The mechanical exhaust for the ventilation of a gasoline machinery space, required...

  10. 46 CFR 185.352 - Ventilation of gasoline machinery spaces.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Ventilation of gasoline machinery spaces. 185.352... (UNDER 100 GROSS TONS) OPERATIONS Miscellaneous Operating Requirements § 185.352 Ventilation of gasoline machinery spaces. The mechanical exhaust for the ventilation of a gasoline machinery space, required...

  11. 46 CFR 97.30-5 - Accidents to machinery.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Accidents to machinery. 97.30-5 Section 97.30-5 Shipping... Reports of Accidents, Repairs, and Unsafe Equipment § 97.30-5 Accidents to machinery. (a) In the event of an accident to a boiler, unfired pressure vessel, or machinery tending to render the further use...

  12. 46 CFR 97.30-5 - Accidents to machinery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Accidents to machinery. 97.30-5 Section 97.30-5 Shipping... Reports of Accidents, Repairs, and Unsafe Equipment § 97.30-5 Accidents to machinery. (a) In the event of an accident to a boiler, unfired pressure vessel, or machinery tending to render the further use...

  13. 46 CFR 196.30-5 - Accidents to machinery.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Accidents to machinery. 196.30-5 Section 196.30-5... Reports of Accidents, Repairs, and Unsafe Equipment § 196.30-5 Accidents to machinery. (a) In the event of an accident to a boiler, unfired pressure vessel, or machinery tending to render the further use...

  14. 46 CFR 196.30-5 - Accidents to machinery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Accidents to machinery. 196.30-5 Section 196.30-5... Reports of Accidents, Repairs, and Unsafe Equipment § 196.30-5 Accidents to machinery. (a) In the event of an accident to a boiler, unfired pressure vessel, or machinery tending to render the further use...

  15. 46 CFR 196.30-5 - Accidents to machinery.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Accidents to machinery. 196.30-5 Section 196.30-5... Reports of Accidents, Repairs, and Unsafe Equipment § 196.30-5 Accidents to machinery. (a) In the event of an accident to a boiler, unfired pressure vessel, or machinery tending to render the further use...

  16. 46 CFR 97.30-5 - Accidents to machinery.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Accidents to machinery. 97.30-5 Section 97.30-5 Shipping... Reports of Accidents, Repairs, and Unsafe Equipment § 97.30-5 Accidents to machinery. (a) In the event of an accident to a boiler, unfired pressure vessel, or machinery tending to render the further use...

  17. 46 CFR 97.30-5 - Accidents to machinery.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 4 2014-10-01 2014-10-01 false Accidents to machinery. 97.30-5 Section 97.30-5 Shipping... Reports of Accidents, Repairs, and Unsafe Equipment § 97.30-5 Accidents to machinery. (a) In the event of an accident to a boiler, unfired pressure vessel, or machinery tending to render the further use...

  18. 46 CFR 196.30-5 - Accidents to machinery.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Accidents to machinery. 196.30-5 Section 196.30-5... Reports of Accidents, Repairs, and Unsafe Equipment § 196.30-5 Accidents to machinery. (a) In the event of an accident to a boiler, unfired pressure vessel, or machinery tending to render the further use...

  19. 46 CFR 196.30-5 - Accidents to machinery.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Accidents to machinery. 196.30-5 Section 196.30-5... Reports of Accidents, Repairs, and Unsafe Equipment § 196.30-5 Accidents to machinery. (a) In the event of an accident to a boiler, unfired pressure vessel, or machinery tending to render the further use...

  20. 46 CFR 97.30-5 - Accidents to machinery.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Accidents to machinery. 97.30-5 Section 97.30-5 Shipping... Reports of Accidents, Repairs, and Unsafe Equipment § 97.30-5 Accidents to machinery. (a) In the event of an accident to a boiler, unfired pressure vessel, or machinery tending to render the further use...

  1. 46 CFR 171.095 - Machinery space bulkhead.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Machinery space bulkhead. 171.095 Section 171.095... PERTAINING TO VESSELS CARRYING PASSENGERS Additional Subdivision Requirements § 171.095 Machinery space... transverse watertight bulkheads to separate the machinery space from the remainder of the vessel. All...

  2. 46 CFR 171.095 - Machinery space bulkhead.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Machinery space bulkhead. 171.095 Section 171.095... PERTAINING TO VESSELS CARRYING PASSENGERS Additional Subdivision Requirements § 171.095 Machinery space... transverse watertight bulkheads to separate the machinery space from the remainder of the vessel. All...

  3. 33 CFR 157.39 - Machinery space bilges.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Machinery space bilges. 157.39... Vessel Operation § 157.39 Machinery space bilges. (a) A tank vessel may discharge an oily mixture from a machinery space bilge that is combined with an oil cargo residue if the vessel discharges in compliance with...

  4. 46 CFR 171.095 - Machinery space bulkhead.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Machinery space bulkhead. 171.095 Section 171.095... PERTAINING TO VESSELS CARRYING PASSENGERS Additional Subdivision Requirements § 171.095 Machinery space... transverse watertight bulkheads to separate the machinery space from the remainder of the vessel. All...

  5. 33 CFR 157.39 - Machinery space bilges.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Machinery space bilges. 157.39... Vessel Operation § 157.39 Machinery space bilges. (a) A tank vessel may discharge an oily mixture from a machinery space bilge that is combined with an oil cargo residue if the vessel discharges in compliance with...

  6. 33 CFR 157.39 - Machinery space bilges.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Machinery space bilges. 157.39... Vessel Operation § 157.39 Machinery space bilges. (a) A tank vessel may discharge an oily mixture from a machinery space bilge that is combined with an oil cargo residue if the vessel discharges in compliance with...

  7. 46 CFR 185.352 - Ventilation of gasoline machinery spaces.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Ventilation of gasoline machinery spaces. 185.352... machinery spaces. The mechanical exhaust for the ventilation of a gasoline machinery space, required by... sufficient to insure at least one complete change of air in the space served. ...

  8. 29 CFR 1915.165 - Ship's deck machinery.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 7 2012-07-01 2012-07-01 false Ship's deck machinery. 1915.165 Section 1915.165 Labor... (CONTINUED) OCCUPATIONAL SAFETY AND HEALTH STANDARDS FOR SHIPYARD EMPLOYMENT Ship's Machinery and Piping Systems § 1915.165 Ship's deck machinery. (a) Before work is performed on the anchor windlass or any of...

  9. 29 CFR 1915.165 - Ship's deck machinery.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 7 2013-07-01 2013-07-01 false Ship's deck machinery. 1915.165 Section 1915.165 Labor... (CONTINUED) OCCUPATIONAL SAFETY AND HEALTH STANDARDS FOR SHIPYARD EMPLOYMENT Ship's Machinery and Piping Systems § 1915.165 Ship's deck machinery. (a) Before work is performed on the anchor windlass or any of...

  10. 30 CFR 57.14205 - Machinery, equipment, and tools.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Machinery, equipment, and tools. 57.14205... and Equipment Safety Practices and Operational Procedures § 57.14205 Machinery, equipment, and tools. Machinery, equipment, and tools shall not be used beyond the design capacity intended by the...

  11. 30 CFR 56.14205 - Machinery, equipment, and tools.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Machinery, equipment, and tools. 56.14205... Equipment Safety Practices and Operational Procedures § 56.14205 Machinery, equipment, and tools. Machinery, equipment, and tools shall not be used beyond the design capacity intended by the manufacturer where...

  12. 30 CFR 56.14205 - Machinery, equipment, and tools.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Machinery, equipment, and tools. 56.14205... Equipment Safety Practices and Operational Procedures § 56.14205 Machinery, equipment, and tools. Machinery, equipment, and tools shall not be used beyond the design capacity intended by the manufacturer where...

  13. 30 CFR 57.14205 - Machinery, equipment, and tools.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Machinery, equipment, and tools. 57.14205... and Equipment Safety Practices and Operational Procedures § 57.14205 Machinery, equipment, and tools. Machinery, equipment, and tools shall not be used beyond the design capacity intended by the...

  14. 46 CFR 109.205 - Inspection of boilers and machinery.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Inspection of boilers and machinery. 109.205 Section 109... OPERATIONS Tests, Drills, and Inspections § 109.205 Inspection of boilers and machinery. The chief engineer or engineer in charge, before he assumes charge of the boilers and machinery of a unit shall inspect...

  15. 46 CFR 109.205 - Inspection of boilers and machinery.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Inspection of boilers and machinery. 109.205 Section 109... OPERATIONS Tests, Drills, and Inspections § 109.205 Inspection of boilers and machinery. The chief engineer or engineer in charge, before he assumes charge of the boilers and machinery of a unit shall inspect...

  16. 46 CFR 109.205 - Inspection of boilers and machinery.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 4 2014-10-01 2014-10-01 false Inspection of boilers and machinery. 109.205 Section 109... OPERATIONS Tests, Drills, and Inspections § 109.205 Inspection of boilers and machinery. The chief engineer or engineer in charge, before he assumes charge of the boilers and machinery of a unit shall inspect...

  17. 46 CFR 109.205 - Inspection of boilers and machinery.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Inspection of boilers and machinery. 109.205 Section 109... OPERATIONS Tests, Drills, and Inspections § 109.205 Inspection of boilers and machinery. The chief engineer or engineer in charge, before he assumes charge of the boilers and machinery of a unit shall inspect...

  18. 29 CFR 1915.165 - Ship's deck machinery.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 7 2011-07-01 2011-07-01 false Ship's deck machinery. 1915.165 Section 1915.165 Labor... (CONTINUED) OCCUPATIONAL SAFETY AND HEALTH STANDARDS FOR SHIPYARD EMPLOYMENT Ship's Machinery and Piping Systems § 1915.165 Ship's deck machinery. (a) Before work is performed on the anchor windlass or any...

  19. 46 CFR 252.33 - Hull and machinery insurance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false Hull and machinery insurance. 252.33 Section 252.33... Subsidy Rates § 252.33 Hull and machinery insurance. (a) Subsidy items. The fair and reasonable net premium costs (including stamp taxes) of hull and machinery, increased value, excess general average...

  20. 46 CFR 282.23 - Hull and machinery insurance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false Hull and machinery insurance. 282.23 Section 282.23... COMMERCE OF THE UNITED STATES Calculation of Subsidy Rates § 282.23 Hull and machinery insurance. (a) Subsidy items. The fair and reasonable net premium costs (including stamp taxes) of hull and machinery...

  1. 29 CFR 1910.214 - Cooperage machinery. [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 5 2013-07-01 2013-07-01 false Cooperage machinery. 1910.214 Section 1910.214 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR OCCUPATIONAL SAFETY AND HEALTH STANDARDS Machinery and Machine Guarding § 1910.214 Cooperage machinery....

  2. 33 CFR 157.39 - Machinery space bilges.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Machinery space bilges. 157.39... Vessel Operation § 157.39 Machinery space bilges. (a) A tank vessel may discharge an oily mixture from a machinery space bilge that is combined with an oil cargo residue if the vessel discharges in compliance...

  3. 46 CFR 171.095 - Machinery space bulkhead.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Machinery space bulkhead. 171.095 Section 171.095... PERTAINING TO VESSELS CARRYING PASSENGERS Additional Subdivision Requirements § 171.095 Machinery space... transverse watertight bulkheads to separate the machinery space from the remainder of the vessel....

  4. 33 CFR 157.39 - Machinery space bilges.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Machinery space bilges. 157.39... Vessel Operation § 157.39 Machinery space bilges. (a) A tank vessel may discharge an oily mixture from a machinery space bilge that is combined with an oil cargo residue if the vessel discharges in compliance...

  5. 46 CFR 171.095 - Machinery space bulkhead.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Machinery space bulkhead. 171.095 Section 171.095... PERTAINING TO VESSELS CARRYING PASSENGERS Additional Subdivision Requirements § 171.095 Machinery space... transverse watertight bulkheads to separate the machinery space from the remainder of the vessel....

  6. 46 CFR 185.352 - Ventilation of gasoline machinery spaces.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Ventilation of gasoline machinery spaces. 185.352... machinery spaces. The mechanical exhaust for the ventilation of a gasoline machinery space, required by... sufficient to insure at least one complete change of air in the space served....

  7. 29 CFR 1910.215 - Abrasive wheel machinery.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 5 2012-07-01 2012-07-01 false Abrasive wheel machinery. 1910.215 Section 1910.215 Labor... OCCUPATIONAL SAFETY AND HEALTH STANDARDS Machinery and Machine Guarding § 1910.215 Abrasive wheel machinery. (a) General requirements—(1) Machine guarding. Abrasive wheels shall be used only on machines provided...

  8. 29 CFR 1910.215 - Abrasive wheel machinery.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 5 2014-07-01 2014-07-01 false Abrasive wheel machinery. 1910.215 Section 1910.215 Labor... OCCUPATIONAL SAFETY AND HEALTH STANDARDS Machinery and Machine Guarding § 1910.215 Abrasive wheel machinery. (a) General requirements—(1) Machine guarding. Abrasive wheels shall be used only on machines provided...

  9. 29 CFR 1910.215 - Abrasive wheel machinery.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 5 2013-07-01 2013-07-01 false Abrasive wheel machinery. 1910.215 Section 1910.215 Labor... OCCUPATIONAL SAFETY AND HEALTH STANDARDS Machinery and Machine Guarding § 1910.215 Abrasive wheel machinery. (a) General requirements—(1) Machine guarding. Abrasive wheels shall be used only on machines provided...

  10. 29 CFR 1910.215 - Abrasive wheel machinery.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 5 2011-07-01 2011-07-01 false Abrasive wheel machinery. 1910.215 Section 1910.215 Labor... OCCUPATIONAL SAFETY AND HEALTH STANDARDS Machinery and Machine Guarding § 1910.215 Abrasive wheel machinery. (a) General requirements—(1) Machine guarding. Abrasive wheels shall be used only on machines provided...

  11. 29 CFR 1910.215 - Abrasive wheel machinery.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 5 2010-07-01 2010-07-01 false Abrasive wheel machinery. 1910.215 Section 1910.215 Labor... OCCUPATIONAL SAFETY AND HEALTH STANDARDS Machinery and Machine Guarding § 1910.215 Abrasive wheel machinery. (a) General requirements—(1) Machine guarding. Abrasive wheels shall be used only on machines provided...

  12. 46 CFR 58.01-20 - Machinery guards.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Machinery guards. 58.01-20 Section 58.01-20 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MAIN AND AUXILIARY MACHINERY AND RELATED SYSTEMS General Requirements § 58.01-20 Machinery guards. Gears, couplings, flywheels and...

  13. 46 CFR 58.01-20 - Machinery guards.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 2 2014-10-01 2014-10-01 false Machinery guards. 58.01-20 Section 58.01-20 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MAIN AND AUXILIARY MACHINERY AND RELATED SYSTEMS General Requirements § 58.01-20 Machinery guards. Gears, couplings, flywheels and...

  14. 46 CFR 58.01-20 - Machinery guards.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 2 2012-10-01 2012-10-01 false Machinery guards. 58.01-20 Section 58.01-20 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MAIN AND AUXILIARY MACHINERY AND RELATED SYSTEMS General Requirements § 58.01-20 Machinery guards. Gears, couplings, flywheels and...

  15. 46 CFR 58.01-20 - Machinery guards.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 2 2011-10-01 2011-10-01 false Machinery guards. 58.01-20 Section 58.01-20 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MAIN AND AUXILIARY MACHINERY AND RELATED SYSTEMS General Requirements § 58.01-20 Machinery guards. Gears, couplings, flywheels and...

  16. 46 CFR 58.01-20 - Machinery guards.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Machinery guards. 58.01-20 Section 58.01-20 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MAIN AND AUXILIARY MACHINERY AND RELATED SYSTEMS General Requirements § 58.01-20 Machinery guards. Gears, couplings, flywheels and...

  17. 29 CFR 1910.214 - Cooperage machinery. [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 5 2011-07-01 2011-07-01 false Cooperage machinery. 1910.214 Section 1910.214 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR OCCUPATIONAL SAFETY AND HEALTH STANDARDS Machinery and Machine Guarding § 1910.214 Cooperage machinery....

  18. Power electronics and electric machinery challenges and opportunities in electric and hybrid vehicles

    SciTech Connect

    Adams, D.J.; Hsu, J.S.; Young, R.W.; Peng, F.Z.

    1997-06-01

    The development of power electronics and electric machinery presents significant challenges to the advancement of electric and hybrid vehicles. Electronic components and systems development for vehicle applications have progressed from the replacement of mechanical systems to the availability of features that can only be realized through interacting electronic controls and devices. Near-term applications of power electronics in vehicles will enable integrated powertrain controls, integrated chassis system controls, and navigation and communications systems. Future applications of optimized electric machinery will enable highly efficient and lightweight systems. This paper will explore the areas where research and development is required to ensure the continued development of power electronics and electric machines to meet the rigorous demands of automotive applications. Additionally, recent advances in automotive related power electronics and electric machinery at Oak Ridge National Laboratory will be explained. 3 refs., 5 figs.

  19. Double-strand conformation polymorphism (DSCP) analysis of the mitochondrial control region generates highly variable markers for population studies in a social insect.

    PubMed

    Atkinson, L; Adams, E S

    1997-11-01

    Genetic markers were obtained for the termite Nasutitermes corniger by DSCP (double-strand conformation polymorphism) analysis of PCR-amplified mitochondrial control region DNA. This procedure revealed twenty-one haplotypes in forty-four colonies, whereas a restriction fragment length polymorphism analysis detected only nine haplotypes. Sequence analysis of DSCP fragments of contrasting mobilities suggests that the electrophoretic haplotypes are caused by DNA curvature in this highly AT-rich region. DSCP markers showed that some termite colonies contained maternally unrelated queens, each of which produced worker offspring. This pattern is consistent with nest founding by unrelated queens. Due to the availability of conserved primers for the mtDNA control region, DSCP analysis may readily reveal comparatively high levels of variation in a wide variety of organisms.

  20. Opportunities for on-line machinery sensing

    SciTech Connect

    Murray, S.F.; Ling, F.F.

    1996-11-01

    While most engineers were concerned with progress in the development of robots and robotic devices, there has been a revolution going on in sensor technology. Micro-sensor devices, so small that they could be encapsulated easily, and so light they could resist high g forces and impacts, are being developed for a variety of applications especially aerospace, automotive and consumer durables. In the field of tribology, the ability of sensors to gather and process information promises real advances in monitoring and sensing potential problems with machinery and with tools. Yet, there are many critical applications where no failure detection devices are being used or even considered. There is a need for more training and better dissemination of know-how for the various types of sensors. This paper is a review of the recent literature on in-situ micro-sensors that might have relevance to machinery condition sensing.

  1. The Autophagic Machinery in Enterovirus Infection.

    PubMed

    Lai, Jeffrey K F; Sam, I-Ching; Chan, Yoke Fun

    2016-01-27

    The Enterovirus genus of the Picornaviridae family comprises many important human pathogens, including polioviruses, rhinovirus, enterovirus A71, and enterovirus D68. They cause a wide variety of diseases, ranging from mild to severe life-threatening diseases. Currently, no effective vaccine is available against enteroviruses except for poliovirus. Enteroviruses subvert the autophagic machinery to benefit their assembly, maturation, and exit from host. Some enteroviruses spread between cells via a process described as autophagosome-mediated exit without lysis (AWOL). The early and late phases of autophagy are regulated through various lipids and their metabolizing enzymes. Some of these lipids and enzymes are specifically regulated by enteroviruses. In the present review, we summarize the current understanding of the regulation of autophagic machinery by enteroviruses, and provide updates on recent developments in this field.

  2. Thermal spray manual for machinery components

    SciTech Connect

    Travis, R.; Ginther, C.; Herbstritt, M.; Herbstritt, J.

    1995-12-31

    The Thermal Spray Manual For Machinery Components is a National Shipbuilding Research (SP-7) Project. This Manual is being developed by Puget Sound Naval Shipyard with the help of other government thermal spray facilities and SP-7 panel members. The purpose of the manual is to provide marine repair facilities with a ``how to do`` document that will be ``user friendly`` and known to be technically sound through production experience. The manual`s intent is to give marine repair facilities the ability to maximize the thermal spray process as a repair method for machinery components and to give these facilities guidelines on how to become qualified to receive certification that they meet the requirements of Military Standard 1687A.

  3. Laser-optic instruments improve machinery alignment

    SciTech Connect

    Bloch, H.P.

    1987-10-12

    Laser-optic alignment systems are fast becoming cost-effective devices that improve the accuracy and speed of machinery shaft alignment. Because of the difficulty, if not impossibility, of aligning operating machinery, cold alignment specifications must be determined to compensate for thermal growth so that the shaft alignment remains within tolerances when the machine reaches normal operating temperature. Some methods for accomplishing this are reviewed here. Three years' field experience with laser-optic alignment systems shows that many of these limitations can be eliminated, resulting in a more accurate alignment in less time. Some actual field alignments are given as examples of the improvement achieved by the use of laser equipment, and a procedure is given that shows how the laser-optic system may be used to determine running alignment changes caused by thermal growth.

  4. The Autophagic Machinery in Enterovirus Infection

    PubMed Central

    Lai, Jeffrey K. F.; Sam, I-Ching; Chan, Yoke Fun

    2016-01-01

    The Enterovirus genus of the Picornaviridae family comprises many important human pathogens, including polioviruses, rhinovirus, enterovirus A71, and enterovirus D68. They cause a wide variety of diseases, ranging from mild to severe life-threatening diseases. Currently, no effective vaccine is available against enteroviruses except for poliovirus. Enteroviruses subvert the autophagic machinery to benefit their assembly, maturation, and exit from host. Some enteroviruses spread between cells via a process described as autophagosome-mediated exit without lysis (AWOL). The early and late phases of autophagy are regulated through various lipids and their metabolizing enzymes. Some of these lipids and enzymes are specifically regulated by enteroviruses. In the present review, we summarize the current understanding of the regulation of autophagic machinery by enteroviruses, and provide updates on recent developments in this field. PMID:26828514

  5. Materials Research for Superconducting Machinery-IV

    DTIC Science & Technology

    1975-09-01

    LABORATORIES Preparation of a Handbook on Mechanical , Thermal, Electrical, and Magnetic properties of Materials for Superconducting Machinery. Eldridge, E. A...Properties of Structural Materials Program Area Mechanical Properties 1. Fracture and Fitigue a. Materials Group Second Year Program (FY 75...crack growth rate tests from 4-300 K on structural alloys, and the effects of stress level and frequency. Mechanical , magnetic, electrical loss

  6. Conformational control inhibition of the BCR-ABL1 tyrosine kinase, including the gatekeeper T315I mutant, by the switch-control inhibitor DCC-2036

    PubMed Central

    Chan, Wayne W.; Wise, Scott C.; Kaufman, Michael D.; Ahn, Yu Mi; Ensinger, Carol L.; Haack, Torsten; Hood, Molly M.; Jones, Jennifer; Lord, John W.; Lu, Wei Ping; Miller, David; Patt, William C.; Smith, Bryan D.; Petillo, Peter A.; Rutkoski, Thomas J.; Telikepalli, Hanumaiah; Vogeti, Lakshminarayana; Yao, Tony; Chun, Lawrence; Clark, Robin; Evangelista, Peter; Gavrilescu, L. Cristina; Lazarides, Katherine; Zaleskas, Virginia M.; Stewart, Lance J.; Van Etten, Richard A.; Flynn, Daniel L.

    2011-01-01

    Summary Acquired resistance to ABL1 tyrosine kinase inhibitors (TKIs) through ABL1 kinase domain mutations, particularly the gatekeeper mutant T315I, is a significant problem for chronic myeloid leukemia (CML) patients. Using structure-based drug design, we developed compounds that bind to residues (Arg386/Glu282) ABL1 uses to switch between inactive and active conformations. The lead “switch-control” inhibitor, DCC-2036, potently inhibits both unphosphorylated and phosphorylated ABL1 by inducing a type II inactive conformation, and retains efficacy against the majority of clinically relevant CML resistance mutants, including T315I. DCC-2036 inhibits BCR-ABL1T315I-expressing cell lines, prolongs survival in mouse models of T315I-mutant CML and B-lymphoblastic leukemia, and inhibits primary patient leukemia cells expressing T315I in vitro and in vivo, supporting its clinical development in TKI-resistant Ph+ leukemia. PMID:21481795

  7. 3D conformal MRI-controlled transurethral ultrasound prostate therapy: validation of numerical simulations and demonstration in tissue-mimicking gel phantoms.

    PubMed

    Burtnyk, Mathieu; N'Djin, William Apoutou; Kobelevskiy, Ilya; Bronskill, Michael; Chopra, Rajiv

    2010-11-21

    MRI-controlled transurethral ultrasound therapy uses a linear array of transducer elements and active temperature feedback to create volumes of thermal coagulation shaped to predefined prostate geometries in 3D. The specific aims of this work were to demonstrate the accuracy and repeatability of producing large volumes of thermal coagulation (>10 cc) that conform to 3D human prostate shapes in a tissue-mimicking gel phantom, and to evaluate quantitatively the accuracy with which numerical simulations predict these 3D heating volumes under carefully controlled conditions. Eleven conformal 3D experiments were performed in a tissue-mimicking phantom within a 1.5T MR imager to obtain non-invasive temperature measurements during heating. Temperature feedback was used to control the rotation rate and ultrasound power of transurethral devices with up to five 3.5 × 5 mm active transducer elements. Heating patterns shaped to human prostate geometries were generated using devices operating at 4.7 or 8.0 MHz with surface acoustic intensities of up to 10 W cm(-2). Simulations were informed by transducer surface velocity measurements acquired with a scanning laser vibrometer enabling improved calculations of the acoustic pressure distribution in a gel phantom. Temperature dynamics were determined according to a FDTD solution to Pennes' BHTE. The 3D heating patterns produced in vitro were shaped very accurately to the prostate target volumes, within the spatial resolution of the MRI thermometry images. The volume of the treatment difference falling outside ± 1 mm of the target boundary was, on average, 0.21 cc or 1.5% of the prostate volume. The numerical simulations predicted the extent and shape of the coagulation boundary produced in gel to within (mean ± stdev [min, max]): 0.5 ± 0.4 [-1.0, 2.1] and -0.05 ± 0.4 [-1.2, 1.4] mm for the treatments at 4.7 and 8.0 MHz, respectively. The temperatures across all MRI thermometry images were predicted within -0.3 ± 1.6 °C and 0

  8. 3D conformal MRI-controlled transurethral ultrasound prostate therapy: validation of numerical simulations and demonstration in tissue-mimicking gel phantoms

    NASA Astrophysics Data System (ADS)

    Burtnyk, Mathieu; Apoutou N'Djin, William; Kobelevskiy, Ilya; Bronskill, Michael; Chopra, Rajiv

    2010-11-01

    MRI-controlled transurethral ultrasound therapy uses a linear array of transducer elements and active temperature feedback to create volumes of thermal coagulation shaped to predefined prostate geometries in 3D. The specific aims of this work were to demonstrate the accuracy and repeatability of producing large volumes of thermal coagulation (>10 cc) that conform to 3D human prostate shapes in a tissue-mimicking gel phantom, and to evaluate quantitatively the accuracy with which numerical simulations predict these 3D heating volumes under carefully controlled conditions. Eleven conformal 3D experiments were performed in a tissue-mimicking phantom within a 1.5T MR imager to obtain non-invasive temperature measurements during heating. Temperature feedback was used to control the rotation rate and ultrasound power of transurethral devices with up to five 3.5 × 5 mm active transducer elements. Heating patterns shaped to human prostate geometries were generated using devices operating at 4.7 or 8.0 MHz with surface acoustic intensities of up to 10 W cm-2. Simulations were informed by transducer surface velocity measurements acquired with a scanning laser vibrometer enabling improved calculations of the acoustic pressure distribution in a gel phantom. Temperature dynamics were determined according to a FDTD solution to Pennes' BHTE. The 3D heating patterns produced in vitro were shaped very accurately to the prostate target volumes, within the spatial resolution of the MRI thermometry images. The volume of the treatment difference falling outside ±1 mm of the target boundary was, on average, 0.21 cc or 1.5% of the prostate volume. The numerical simulations predicted the extent and shape of the coagulation boundary produced in gel to within (mean ± stdev [min, max]): 0.5 ± 0.4 [-1.0, 2.1] and -0.05 ± 0.4 [-1.2, 1.4] mm for the treatments at 4.7 and 8.0 MHz, respectively. The temperatures across all MRI thermometry images were predicted within -0.3 ± 1.6 °C and 0

  9. The exportomer: the peroxisomal receptor export machinery.

    PubMed

    Platta, Harald W; Hagen, Stefanie; Erdmann, Ralf

    2013-04-01

    Peroxisomes constitute a dynamic compartment of almost all eukaryotic cells. Depending on environmental changes and cellular demands peroxisomes can acquire diverse metabolic roles. The compartmentalization of peroxisomal matrix enzymes is a prerequisite to carry out their physiologic function. The matrix proteins are synthesized on free ribosomes in the cytosol and are ferried to the peroxisomal membrane by specific soluble receptors. Subsequent to cargo release into the peroxisomal matrix, the receptors are exported back to the cytosol to facilitate further rounds of matrix protein import. This dislocation step is accomplished by a remarkable machinery, which comprises enzymes required for the ubiquitination as well as the ATP-dependent extraction of the receptor from the membrane. Interestingly, receptor ubiquitination and dislocation are the only known energy-dependent steps in the peroxisomal matrix protein import process. The current view is that the export machinery of the receptors might function as molecular motor not only in the dislocation of the receptors but also in the import step of peroxisomal matrix protein by coupling ATP-dependent removal of the peroxisomal import receptor with cargo translocation into the organelle. In this review we will focus on the architecture and function of the peroxisomal receptor export machinery, the peroxisomal exportomer.

  10. The C-terminal region of the motor protein MCAK controls its structure and activity through a conformational switch.

    PubMed

    Talapatra, Sandeep K; Harker, Bethany; Welburn, Julie P I

    2015-04-27

    The precise regulation of microtubule dynamics is essential during cell division. The kinesin-13 motor protein MCAK is a potent microtubule depolymerase. The divergent non-motor regions flanking the ATPase domain are critical in regulating its targeting and activity. However, the molecular basis for the function of the non-motor regions within the context of full-length MCAK is unknown. Here, we determine the structure of MCAK motor domain bound to its regulatory C-terminus. Our analysis reveals that the MCAK C-terminus binds to two motor domains in solution and is displaced allosterically upon microtubule binding, which allows its robust accumulation at microtubule ends. These results demonstrate that MCAK undergoes long-range conformational changes involving its C-terminus during the soluble to microtubule-bound transition and that the C-terminus-motor interaction represents a structural intermediate in the MCAK catalytic cycle. Together, our work reveals intrinsic molecular mechanisms underlying the regulation of kinesin-13 activity.

  11. Conformational Dynamics of the Focal Adhesion Targeting Domain Control Specific Functions of Focal Adhesion Kinase in Cells*

    PubMed Central

    Kadaré, Gress; Gervasi, Nicolas; Brami-Cherrier, Karen; Blockus, Heike; El Messari, Said; Arold, Stefan T.; Girault, Jean-Antoine

    2015-01-01

    Focal adhesion (FA) kinase (FAK) regulates cell survival and motility by transducing signals from membrane receptors. The C-terminal FA targeting (FAT) domain of FAK fulfils multiple functions, including recruitment to FAs through paxillin binding. Phosphorylation of FAT on Tyr925 facilitates FA disassembly and connects to the MAPK pathway through Grb2 association, but requires dissociation of the first helix (H1) of the four-helix bundle of FAT. We investigated the importance of H1 opening in cells by comparing the properties of FAK molecules containing wild-type or mutated FAT with impaired or facilitated H1 openings. These mutations did not alter the activation of FAK, but selectively affected its cellular functions, including self-association, Tyr925 phosphorylation, paxillin binding, and FA targeting and turnover. Phosphorylation of Tyr861, located between the kinase and FAT domains, was also enhanced by the mutation that opened the FAT bundle. Similarly phosphorylation of Ser910 by ERK in response to bombesin was increased by FAT opening. Although FAK molecules with the mutation favoring FAT opening were poorly recruited at FAs, they efficiently restored FA turnover and cell shape in FAK-deficient cells. In contrast, the mutation preventing H1 opening markedly impaired FAK function. Our data support the biological importance of conformational dynamics of the FAT domain and its functional interactions with other parts of the molecule. PMID:25391654

  12. The C-terminal region of the motor protein MCAK controls its structure and activity through a conformational switch

    PubMed Central

    Talapatra, Sandeep K; Harker, Bethany; Welburn, Julie PI

    2015-01-01

    The precise regulation of microtubule dynamics is essential during cell division. The kinesin-13 motor protein MCAK is a potent microtubule depolymerase. The divergent non-motor regions flanking the ATPase domain are critical in regulating its targeting and activity. However, the molecular basis for the function of the non-motor regions within the context of full-length MCAK is unknown. Here, we determine the structure of MCAK motor domain bound to its regulatory C-terminus. Our analysis reveals that the MCAK C-terminus binds to two motor domains in solution and is displaced allosterically upon microtubule binding, which allows its robust accumulation at microtubule ends. These results demonstrate that MCAK undergoes long-range conformational changes involving its C-terminus during the soluble to microtubule-bound transition and that the C-terminus-motor interaction represents a structural intermediate in the MCAK catalytic cycle. Together, our work reveals intrinsic molecular mechanisms underlying the regulation of kinesin-13 activity. DOI: http://dx.doi.org/10.7554/eLife.06421.001 PMID:25915621

  13. Steinberg conformal algebras

    NASA Astrophysics Data System (ADS)

    Mikhalev, A. V.; Pinchuk, I. A.

    2005-06-01

    The structure of Steinberg conformal algebras is studied; these are analogues of Steinberg groups (algebras, superalgebras).A Steinberg conformal algebra is defined as an abstract algebra by a system of generators and relations between the generators. It is proved that a Steinberg conformal algebra is the universal central extension of the corresponding conformal Lie algebra; the kernel of this extension is calculated.

  14. Polymer modeling of the E. coli genome reveals the involvement of locus positioning and macrodomain structuring for the control of chromosome conformation and segregation

    PubMed Central

    Junier, Ivan; Boccard, Frédéric; Espéli, Olivier

    2014-01-01

    The mechanisms that control chromosome conformation and segregation in bacteria have not yet been elucidated. In Escherichia coli, the mere presence of an active process remains an open question. Here, we investigate the conformation and segregation pattern of the E. coli genome by performing numerical simulations on a polymer model of the chromosome. We analyze the roles of the intrinsic structuring of chromosomes and the forced localization of specific loci, which are observed in vivo. Specifically, we examine the segregation pattern of a chromosome that is divided into four structured macrodomains (MDs) and two non-structured regions. We find that strong osmotic-like organizational forces, which stem from the differential condensation levels of the chromosome regions, dictate the cellular disposition of the chromosome. Strikingly, the comparison of our in silico results with fluorescent imaging of the chromosome choreography in vivo reveals that in the presence of MDs the targeting of the origin and terminus regions to specific positions are sufficient to generate a segregation pattern that is indistinguishable from experimentally observed patterns. PMID:24194594

  15. Lattice Simulations and Infrared Conformality

    DOE PAGES

    Appelquist, Thomas; Fleming, George T.; Lin, Meifeng; ...

    2011-09-01

    We examine several recent lattice-simulation data sets, asking whether they are consistent with infrared conformality. We observe, in particular, that for an SU(3) gauge theory with 12 Dirac fermions in the fundamental representation, recent simulation data can be described assuming infrared conformality. Lattice simulations include a fermion mass m which is then extrapolated to zero, and we note that this data can be fit by a small-m expansion, allowing a controlled extrapolation. We also note that the conformal hypothesis does not work well for two theories that are known or expected to be confining and chirally broken, and that itmore » does work well for another theory expected to be infrared conformal.« less

  16. Machinery Vibration Monitoring Program at the Savannah River Site

    SciTech Connect

    Potvin, M.M.

    1990-01-01

    The Reactor Maintenance's Machinery Vibration Monitoring Program (MVMP) plays an essential role in ensuring the safe operation of the three Production Reactors at the Westinghouse Savannah River Company (WRSC) Savannah River Site (SRS). This program has increased machinery availability and reduced maintenance cost by the early detection and determination of machinery problems. This paper presents the Reactor Maintenance's Machinery Vibration Monitoring Program, which has been documented based on Electric Power Research Institute's (EPRI) NP-5311, Utility Machinery Monitoring Guide, and some examples of the successes that it has enjoyed.

  17. 2D EPID dose calibration for pretreatment quality control of conformal and IMRT fields: A simple and fast convolution approach.

    PubMed

    Camilleri, Jérémy; Mazurier, Jocelyne; Franck, Denis; Dudouet, Philippe; Latorzeff, Igor; Franceries, Xavier

    2016-01-01

    This work presents an original algorithm that converts the signal of an electronic portal imaging device (EPID) into absorbed dose in water at the depth of maximum. The model includes a first image pre-processing step that accounts for the non-uniformity of the detector response but also for the perturbation of the signal due to backscatter radiation. Secondly, the image is converted into absorbed dose to water through a linear conversion function associated with a dose redistribution kernel. These two computation parameters were modelled by correlating the on-axis EPID signal with absorbed dose measurements obtained on square fields by using an ionization chamber placed in water at the depth of maximum dose. The accuracy of the algorithm was assessed by comparing the dose determined from the EPID signal with the dose derived by the treatment planning system (TPS) using the ϒ-index. These comparisons were performed on 8 conformal radiotherapy treatment fields (3DCRT) and 18 modulated fields (IMRT). For a dose difference and a distance-to-agreement set to 3% of the maximum dose and 2 mm respectively, the mean percentage of points with a ϒ-value less than or equal to 1 was 99.8% ± 0.1% for 3DCRT fields and 96.8% ± 2.7% for IMRT fields. Moreover, the mean gamma values were always less than 0.5 whatever the treatment technique. These results confirm that our algorithm is an accurate and suitable tool for clinical use in a context of IMRT quality assurance programmes. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  18. Role of the Propeptide in Controlling Conformation and Assembly State of Hepatitis B virus e-antigen

    PubMed Central

    Watts, Norman R.; Conway, James F.; Cheng, Naiqian; Stahl, Stephen J.; Steven, Alasdair C.; Wingfield, Paul T.

    2011-01-01

    Hepatitis B virus “e-antigen” is thought to be a soluble dimeric protein that is associated with chronic infection. It shares 149 residues with the viral capsid protein “core-antigen”, but has an additional ten-residue, hydrophobic, cysteine-containing amino-terminal propeptide whose presence correlates with physical, serological, and immunological differences between the two proteins. In core-antigen dimers, the subunits pair by forming a four-helix bundle stabilized by an inter-molecular disulfide bond. The structure of e-antigen is probably similar, but instead has two intra-molecular disulfide bonds involving the propeptide. To compare the proteins directly, and thereby clarify the role of the propeptide, mutations and solution conditions were identified that render both proteins as either soluble dimers or assembled capsids. Thermally induced unfolding monitored by circular dichroism, and electrophoresis of oxidized and reduced dimers, showed that the propeptide has a destabilizing effect, and that the intra-molecular disulfide bond forms preferentially and blocks the formation of the inter-molecular disulfide bond that otherwise stabilizes the dimer. The e-antigen capsids are less regular than core-antigen capsids; nevertheless, cryo-EM reconstructions confirm that they are constructed of dimers resembling those of core-antigen capsids. In them, a portion of the propeptide is visible near the dimer interface, suggesting that it intercalates there, consistent with the known formation of a disulfide bond between C(−7) in the propeptide and C61 in the dimer interface. However, this intercalation distorts the dimer into an assembly-reluctant conformation. PMID:21463641

  19. Regioselective control of β-d-glucose oxidation by pyranose 2-oxidase is intimately coupled to conformational degeneracy.

    PubMed

    Tan, Tien-Chye; Haltrich, Dietmar; Divne, Christina

    2011-06-17

    Trametes multicolor pyranose 2-oxidase (P2O) is a flavoprotein oxidase that oxidizes d-glucose at C2 to 2-keto-d-glucose by a highly regioselective mechanism. In this work, fluorinated sugar substrates were used as mechanistic probes to investigate the basis of regioselectivity in P2O. Although frequently used to study the mechanisms of glycoside hydrolases, our work provides the first example of applying these probes to sugar oxidoreductases. Our previous structure of the P2O mutant H167A in complex with the slow substrate 2-deoxy-2-fluoro-d-glucose showed a substrate-binding mode compatible with oxidation at C3. To accommodate the sugar, a gating segment, (454)FSY(456), in the substrate recognition loop partly unfolded to create a spacious and more polar active site that is distinct from the closed state of P2O. The crystal structure presented here shows that the preferred C2 oxidation where an ordered complex of P2O H167A with 3-deoxy-3-fluoro-d-glucose at 1.35 Å resolution was successfully trapped. In this semi-open C2-oxidation complex, the substrate recognition loop tightens to form an optimized substrate complex stabilized by interactions between Asp452 and glucose O4, as well as Tyr456 and the glucose O6 group, interactions that are not possible when glucose is positioned for oxidation at C3. The different conformations of the (454)FSY(456) gating segment in the semi-open and closed states induce backbone and side-chain movements of Thr169 and Asp452 that add further differential stabilization to the individual states. We expect the semi-open state (C2-oxidation state) and closed state to be good approximations of the active-site structure during the reductive half-reaction (sugar oxidation) and oxidative half-reaction (O(2) reduction).

  20. Metamaterials with conformational nonlinearity

    PubMed Central

    Lapine, Mikhail; Shadrivov, Ilya V.; Powell, David A.; Kivshar, Yuri S.

    2011-01-01

    Within a decade of fruitful development, metamaterials became a prominent area of research, bridging theoretical and applied electrodynamics, electrical engineering and material science. Being man-made structures, metamaterials offer a particularly useful playground to develop interdisciplinary concepts. Here we demonstrate a novel principle in metamaterial assembly which integrates electromagnetic, mechanical, and thermal responses within their elements. Through these mechanisms, the conformation of the meta-molecules changes, providing a dual mechanism for nonlinearity and offering nonlinear chirality. Our proposal opens a wide road towards further developments of nonlinear metamaterials and photonic structures, adding extra flexibility to their design and control. PMID:22355655

  1. Silicon-based bulky group-induced remote control and conformational preference in the synthesis and application of isolable atropisomeric amides with secondary alcohol or amine moieties.

    PubMed

    Bai, Xing-Feng; Deng, Wen-Hui; Xu, Zheng; Li, Fu-Wei; Deng, Yuan; Xia, Chun-Gu; Xu, Li-Wen

    2014-04-01

    Remote stereocontrol through conformational transmission along a carbon chain is highly important in synthetic systems and molecular architectures. In this work, the interactional reactivity between a remote silicon-based bulky group and an O-/N-containing functional group has been revealed and determined by lateral lithiation-substitution, desilylation, as well as desilylation-olefination with benzaldehyde. The results suggest considerable information transmission and steric hindrance that can be exploited for the controllable synthesis of atropisomeric molecules. Based on the remote steric effect of a functional group across the aromatic ring of an amide, the construction of isolable atropisomeric amides with functional groups, such as alcohol, amine, and olefin was successfully achieved. All these new atropisomers were obtained in reasonable yield in pure diastereomeric form, and the specific configuration of representative products was confirmed by X-ray crystallography. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. 46 CFR 30.10-42 - Machinery space-TB/ALL.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 1 2012-10-01 2012-10-01 false Machinery space-TB/ALL. 30.10-42 Section 30.10-42...-42 Machinery space—TB/ALL. The term machinery space means any space that contains machinery and related equipment including Category A machinery spaces, propelling machinery, boilers, oil fuel units...

  3. 46 CFR 30.10-42 - Machinery space-TB/ALL.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 1 2014-10-01 2014-10-01 false Machinery space-TB/ALL. 30.10-42 Section 30.10-42...-42 Machinery space—TB/ALL. The term machinery space means any space that contains machinery and related equipment including Category A machinery spaces, propelling machinery, boilers, oil fuel units...

  4. 46 CFR 30.10-42 - Machinery space-TB/ALL.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 1 2013-10-01 2013-10-01 false Machinery space-TB/ALL. 30.10-42 Section 30.10-42...-42 Machinery space—TB/ALL. The term machinery space means any space that contains machinery and related equipment including Category A machinery spaces, propelling machinery, boilers, oil fuel units...

  5. 46 CFR 30.10-42 - Machinery space-TB/ALL.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Machinery space-TB/ALL. 30.10-42 Section 30.10-42...-42 Machinery space—TB/ALL. The term machinery space means any space that contains machinery and related equipment including Category A machinery spaces, propelling machinery, boilers, oil fuel...

  6. 46 CFR 30.10-42 - Machinery space-TB/ALL.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 1 2011-10-01 2011-10-01 false Machinery space-TB/ALL. 30.10-42 Section 30.10-42...-42 Machinery space—TB/ALL. The term machinery space means any space that contains machinery and related equipment including Category A machinery spaces, propelling machinery, boilers, oil fuel...

  7. Failure Accommodation Tested in Magnetic Suspension Systems for Rotating Machinery

    NASA Technical Reports Server (NTRS)

    Provenza, Andy J.

    2000-01-01

    The NASA Glenn Research Center at Lewis Field and Texas A&M University are developing techniques for accommodating certain types of failures in magnetic suspension systems used in rotating machinery. In recent years, magnetic bearings have become a viable alternative to rolling element bearings for many applications. For example, industrial machinery such as machine tool spindles and turbomolecular pumps can today be bought off the shelf with magnetically supported rotating components. Nova Gas Transmission Ltd. has large gas compressors in Canada that have been running flawlessly for years on magnetic bearings. To help mature this technology and quiet concerns over the reliability of magnetic bearings, NASA researchers have been investigating ways of making the bearing system tolerant to faults. Since the potential benefits from an oil-free, actively controlled bearing system are so attractive, research that is focused on assuring system reliability and safety is justifiable. With support from the Fast Quiet Engine program, Glenn's Structural Mechanics and Dynamics Branch is working to demonstrate fault-tolerant magnetic suspension systems targeted for aerospace engine applications. The Flywheel Energy Storage Program is also helping to fund this research.

  8. Cellular Functions and Molecular Mechanisms of the ESCRT Membrane-Scission Machinery.

    PubMed

    Christ, Liliane; Raiborg, Camilla; Wenzel, Eva M; Campsteijn, Coen; Stenmark, Harald

    2017-01-01

    The endosomal sorting complex required for transport (ESCRT) machinery is an assembly of protein subcomplexes (ESCRT I-III) that cooperate with the ATPase VPS4 to mediate scission of membrane necks from the inside. The ESCRT machinery has evolved as a multipurpose toolbox for mediating receptor sorting, membrane remodeling, and membrane scission, with ESCRT-III as the major membrane-remodeling component. Cellular membrane scission processes mediated by ESCRT-III include biogenesis of multivesicular endosomes, budding of enveloped viruses, cytokinetic abscission, neuron pruning, plasma membrane wound repair, nuclear pore quality control, nuclear envelope reformation, and nuclear envelope repair. We describe here the involvement of the ESCRT machinery in these processes and review current models for how ESCRT-III-containing multimeric filaments serve to mediate membrane remodeling and scission.

  9. High-dose-rate Three-dimensional Conformal Radiotherapy Combined with Active Breathing Control for Stereotactic Body Radiotherapy of Early-stage Non-small-cell Lung Cancer.

    PubMed

    Wang, Ruozheng; Yin, Yong; Qin, Yonghui; Yu, Jinming

    2015-12-01

    The purpose of this study was to evaluate the feasibility and benefits of using high-dose-rate three-dimensional conformal radiotherapy (3D-CRT) combined with active breathing control (ABC) for stereotactic body radiotherapy (SBRT) of patients with early-stage non-small-cell lung cancer (NSCLC). Eight patients with early-stage NSCLC underwent CT scans under standard free-breathing (FB) and moderately deep inspiration breath-hold (mDIBH) with ABC. Two high-dose-rate 3D-CRT plans (1000 Mu/min) were designed based on the CT scans with FB and mDIBH. The maximal dose (D1%), minimal dose (D99%), conformity index (CI), and homogeneity index (HI) of the planning target volume (PTV), and dose-volume indices of the organs at risk between each plan were compared. The mean PTV volume decreased from 158.04 cm(3) with FB to 76.90 cm(3) with mDIBH (p < 0.05). When mDIBH was used, increases in the affected lung volume (by 47%), contralateral lung volume (by 55%), and total lung volume (by 50%) were observed compared to FB (p < 0.05). The V5-V40 of the affected lung (Vx represented the percentage volume of organs receiving at least the x Gy), V5-V40 and the mean dose for the total lung, V5-V40 and mean dose of the chest wall, and the maximum dose of the spinal cord were less for mDIBH than FB (p < 0.05). There were no significant differences in CI, HI, D1%, or D99% for the PTV between the plans. In conclusion, high-dose-rate 3D-CRT combined with ABC reduced the radiation dose to the lungs and chest wall without affecting the dose distribution in SBRT of early-stage NSCLC patients.

  10. The Autophagic Machinery in Viral Exocytosis

    PubMed Central

    Münz, Christian

    2017-01-01

    The discovery of the molecular machinery of autophagy, namely Atg proteins, was awarded with the Nobel prize in physiology and medicine to Yoshinori Ohsumi in 2016. While this machinery was originally identified by its ability to allow cells to survive starvation via lysosomal degradation to recycle cellular components, it has recently become apparent that it also is used by cells to secrete cytoplasmic constituents. Furthermore, viruses have learned to use this Atg supported exocytosis to exit cells, acquire envelopes in the cytosol and select lipids into their surrounding membranes that might allow for increased robustness of their virions and altered infection behavior. Along these lines, picornaviruses exit infected cells in packages wrapped into autophagic membranes, herpesviruses recruit autophagic membranes into their envelopes and para- as well as orthomyxoviruses redirect autophagic membranes to the cell membrane, which increases the robustness of their envelope that they acquire at this site. These recent findings open a new exciting field on the regulation of degradation vs. release of autophagic membranes and will be discussed in this minireview. PMID:28270807

  11. The Ubiquitination Machinery of the Ubiquitin System

    PubMed Central

    Callis, Judy

    2014-01-01

    The protein ubiquitin is a covalent modifier of proteins, including itself. The ubiquitin system encompasses the enzymes required for catalysing attachment of ubiquitin to substrates as well as proteins that bind to ubiquitinated proteins leading them to their final fate. Also included are activities that remove ubiquitin independent of, or in concert with, proteolysis of the substrate, either by the proteasome or proteases in the vacuole. In addition to ubiquitin encoded by a family of fusion proteins, there are proteins with ubiquitin-like domains, likely forming ubiquitin's β-grasp fold, but incapable of covalent modification. However, they serve as protein-protein interaction platforms within the ubiquitin system. Multi-gene families encode all of these types of activities. Within the ubiquitination machinery “half” of the ubiquitin system are redundant, partially redundant, and unique components affecting diverse developmental and environmental responses in plants. Notably, multiple aspects of biotic and abiotic stress responses require, or are modulated by, ubiquitination. Finally, aspects of the ubiquitin system have broad utility: as components to enhance gene expression or to regulate protein abundance. This review focuses on the ubiquitination machinery: ubiquitin, unique aspects about the synthesis of ubiquitin and organization of its gene family, ubiquitin activating enzymes (E1), ubiquitin conjugating enzymes (E2) and ubiquitin ligases, or E3s. Given the large number of E3s in Arabidopsis this review covers the U box, HECT and RING type E3s, with the exception of the cullin-based E3s. PMID:25320573

  12. The Mendelian disorders of the epigenetic machinery

    PubMed Central

    Bjornsson, Hans Tomas

    2015-01-01

    The Mendelian disorders of the epigenetic machinery are genetic disorders that involve disruption of the various components of the epigenetic machinery (writers, erasers, readers, and remodelers) and are thus expected to have widespread downstream epigenetic consequences. Studying this group may offer a unique opportunity to learn about the role of epigenetics in health and disease. Among these patients, neurological dysfunction and, in particular, intellectual disability appears to be a common phenotype; however, this is often seen in association with other more specific features in respective disorders. The specificity of some of the clinical features raises the question whether specific cell types are particularly sensitive to the loss of these factors. Most of these disorders demonstrate dosage sensitivity as loss of a single allele appears to be sufficient to cause the observed phenotypes. Although the pathogenic sequence is unknown for most of these disorders, there are several examples where disrupted expression of downstream target genes accounts for a substantial portion of the phenotype; hence, it may be useful to systematically map such disease-relevant target genes. Finally, two of these disorders (Rubinstein-Taybi and Kabuki syndromes) have shown post-natal rescue of markers of the neurological dysfunction with drugs that lead to histone deacetylase inhibition, indicating that some of these disorders may be treatable causes of intellectual disability. PMID:26430157

  13. 18. PWD Drawing 1123915 (814M7) (1945), 'Machinery Cleaning Bldg., Bldg ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    18. PWD Drawing 11239-15 (814-M-7) (1945), 'Machinery Cleaning Bldg., Bldg No. 814, Fire Protection Automatic CO2 and Tank Cover Control' - Mare Island Naval Shipyard, Chemical Cleaning Facility, North of Fourteenth Street, between California & Railroad Avenue, Vallejo, Solano County, CA

  14. Protein quality control at the plasma membrane

    PubMed Central

    Okiyoneda, Tsukasa; Apaja, Pirjo M.; Lukacs, Gergely L.

    2011-01-01

    Cellular proteostasis (or protein homeostasis) depends on the timely folding and disposal of conformationally damaged polypeptides during their life span at all subcellular locations. This process is particularly important for membrane proteins confined to the cell surface with critical regulatory role in cellular homoeostasis and intercellular communication. Accumulating evidences indicate that membrane proteins exported from the endoplasmic reticulum (ER) are subjected to peripheral quality control (QC) along the late secretory and endocytic pathways, as well as at the plasma membrane (PM). Recently identified components of the PM QC recognition and effector mechanisms responsible for ubiquitination and lysosomal degradation of conformationally damaged PM proteins uncovered striking similarities to and differences from that of the ER QC machinery. Possible implications of the peripheral protein QC activity in phenotypic modulation of conformational diseases are also outlined. PMID:21571517

  15. Protein quality control at the plasma membrane.

    PubMed

    Okiyoneda, Tsukasa; Apaja, Pirjo M; Lukacs, Gergely L

    2011-08-01

    Cellular proteostasis (or protein homeostasis) depends on the timely folding and disposal of conformationally damaged polypeptides during their life span at all subcellular locations. This process is particularly important for membrane proteins confined to the cell surface with crucial regulatory role in cellular homoeostasis and intercellular communication. Accumulating evidences indicate that membrane proteins exported from the endoplasmic reticulum (ER) are subjected to peripheral quality control (QC) along the late secretory and endocytic pathways, as well as at the plasma membrane (PM). Recently identified components of the PM QC recognition and effector mechanisms responsible for ubiquitination and lysosomal degradation of conformationally damaged PM proteins uncovered striking similarities to and differences from that of the ER QC machinery. Possible implications of the peripheral protein QC activity in phenotypic modulation of conformational diseases are also outlined. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

  16. A photoresponsive soft interface reversibly controls wettability and cell adhesion by conformational changes in a spiropyran-conjugated amphiphilic block copolymer.

    PubMed

    He, Di; Arisaka, Yoshinori; Masuda, Kenichi; Yamamoto, Mitsuya; Takeda, Naoya

    2017-01-18

    The functionalities of soft interfaces including cell adhesion can be enhanced by dynamic conversion of polymer properties and movement via external stimuli. Light is a superior stimulus, and various surfaces modified with photoreactive molecules have been prepared. However, in most of these studies, the surface properties are irreversibly changed due to photo-degradation, and reversible adhesion and collection of cells is not feasible. In this study, we developed a photoresponsive polymer soft interface that was able to spatiotemporally control wettability, cell adhesion, and detachment in a reversible manner. Spiropyran molecules were introduced into the hydrophobic block of an amphiphilic diblock copolymer consisting of poly(methyl methacrylate) and polyethylene glycol, and the monomer unit numbers of these components were optimized. The copolymer was immobilized on a glass substrate as a nanofilm. With alternating irradiation using UV and visible light, the surface exhibited reversible changes in hydrophobicity and hydrophilicity, and the direction of change was opposite to the polarity change in photo-isomerization of spiropyran. We also achieved photo-control of effective cell adhesion and detachment with sequential irradiation with UV and visible light. These remarkable functions could be ascribed to conformational changes triggered by photo-isomerization of spiropyran. This photoresponsive polymer soft interface may have applications as a powerful tool in biological studies by facilitating sequential changes in wettability and bioaffinity.

  17. Strategies for the photo-control of endogenous protein activity.

    PubMed

    Brechun, Katherine E; Arndt, Katja M; Woolley, G Andrew

    2016-11-28

    Photo-controlled or 'optogenetic' effectors interfacing with endogenous protein machinery allow the roles of endogenous proteins to be probed. There are two main approaches being used to develop optogenetic effectors: (i) caging strategies using photo-controlled conformational changes, and (ii) protein relocalization strategies using photo-controlled protein-protein interactions. Numerous specific examples of these approaches have been reported and efforts to develop general methods for photo-control of endogenous proteins are a current focus. The development of improved screening and selection methods for photo-switchable proteins would advance the field.

  18. Conformal thermal therapy using planar ultrasound transducers and adaptive closed-loop MR temperature control: demonstration in gel phantoms and ex vivo tissues

    NASA Astrophysics Data System (ADS)

    Tang, K.; Choy, V.; Chopra, R.; Bronskill, M. J.

    2007-05-01

    MRI-guided transurethral ultrasound therapy offers a minimally invasive approach for the treatment of localized prostate cancer. Integrating a multi-element planar transducer with active MR temperature feedback can enable three-dimensional conformal thermal therapy of a target region within the prostate gland while sparing surrounding normal tissues. Continuous measurement of the temperature distribution in tissue enables dynamic compensation for unknown changes in blood flow and tissue properties during treatment. The main goal of this study was to evaluate the feasibility of using active temperature feedback on a clinical 1.5 T MR imager for conformal thermal therapy. MR thermometry was performed during heating in both gel phantoms and excised tissue with a transurethral heating applicator, and the rotation rate and power were varied based on the thermal measurements. The capability to produce a region of thermal damage that matched a target boundary was evaluated. The influence of a cooling gradient (to simulate cooling of the rectum or urethra) on the desired pattern of thermal damage was also investigated in gel phantoms. Results showed high correlation between the desired target boundary and the 55 °C isotherm generated during heating with an average distance error of 0.9 mm ± 0.4 mm (n = 6) in turkey breasts, 1.4 mm ± 0.6 mm (n = 4) in gel phantoms without rectal cooling and 1.4 mm ± 0.6 mm (n = 3) in gel phantoms with rectal cooling. The results were obtained using a temporal update rate of 5 s, a spatial resolution of 3 × 3 × 10 mm for the control point, and a temperature uncertainty of approximately 1 °C. The performance of the control algorithm under these conditions was comparable to that of simulations conducted previously by our group. Overall, the feasibility of generating targeted regions of thermal damage with a transurethral heating applicator and active MR temperature feedback has been demonstrated experimentally. This method of treatment

  19. Conformal thermal therapy using planar ultrasound transducers and adaptive closed-loop MR temperature control: demonstration in gel phantoms and ex vivo tissues.

    PubMed

    Tang, K; Choy, V; Chopra, R; Bronskill, M J

    2007-05-21

    MRI-guided transurethral ultrasound therapy offers a minimally invasive approach for the treatment of localized prostate cancer. Integrating a multi-element planar transducer with active MR temperature feedback can enable three-dimensional conformal thermal therapy of a target region within the prostate gland while sparing surrounding normal tissues. Continuous measurement of the temperature distribution in tissue enables dynamic compensation for unknown changes in blood flow and tissue properties during treatment. The main goal of this study was to evaluate the feasibility of using active temperature feedback on a clinical 1.5 T MR imager for conformal thermal therapy. MR thermometry was performed during heating in both gel phantoms and excised tissue with a transurethral heating applicator, and the rotation rate and power were varied based on the thermal measurements. The capability to produce a region of thermal damage that matched a target boundary was evaluated. The influence of a cooling gradient (to simulate cooling of the rectum or urethra) on the desired pattern of thermal damage was also investigated in gel phantoms. Results showed high correlation between the desired target boundary and the 55 degrees C isotherm generated during heating with an average distance error of 0.9 mm +/- 0.4 mm (n = 6) in turkey breasts, 1.4 mm +/- 0.6 mm (n = 4) in gel phantoms without rectal cooling and 1.4 mm +/- 0.6 mm (n = 3) in gel phantoms with rectal cooling. The results were obtained using a temporal update rate of 5 s, a spatial resolution of 3 x 3 x 10 mm for the control point, and a temperature uncertainty of approximately 1 degrees C. The performance of the control algorithm under these conditions was comparable to that of simulations conducted previously by our group. Overall, the feasibility of generating targeted regions of thermal damage with a transurethral heating applicator and active MR temperature feedback has been demonstrated experimentally. This method

  20. Autophagy: molecular machinery for self-eating

    PubMed Central

    Yorimitsu, T; Klionsky, DJ

    2006-01-01

    Autophagy is a highly conserved process in eukaryotes in which the cytoplasm, including excess or aberrant organelles, is sequestered into double-membrane vesicles and delivered to the degradative organelle, the lysosome/vacuole, for breakdown and eventual recycling of the resulting macromolecules. This process has an important role in various biological events such as adaptation to changing environmental conditions, cellular remodeling during development and differentiation, and determination of lifespan. Auto-phagy is also involved in preventing certain types of disease, although it may contribute to some pathologies. Recent studies have identified many components that are required to drive this complicated cellular process. Autophagy-related genes were first identified in yeast, but homologs are found in all eukaryotes. Analyses in a range of model systems have provided huge advances toward understanding the molecular basis of autophagy. Here we review our current knowledge on the machinery and molecular mechanism of autophagy. PMID:16247502

  1. Consider synthetic lubricants for process machinery

    SciTech Connect

    Bloch, H.P. , Montgomery, TX ); Pate, A.R. Jr. )

    1995-01-01

    Judicious application of properly formulated synthetic lubricants can benefit a wide spectrum of process machinery. This informed usage is very likely to drive down overall maintenance and downtime expenditures and can markedly improve plant efficiency. The paper describes the origin of synthetic lubricants, then explains the principal features and attributes of the six base fluids: synthetic hydrocarbon fluids; organic esters; polyglycols; phosphate esters; silicones; and blends of the synthetic lubricants. The paper discusses the properties and advantages and gives brief highlights of successful case histories of the use of synthetic lubricants. These include: circulating oil system for furnace air preheaters; Right angle gear drives for fin fan coolers; plant-wide oil mist systems; and pulverizing mills in coal-fired generating plant. In the last case, an economic analysis is done to point out the savings possible in lubricant consumption cost, reduced maintenance cost, lubricant disposal cost, and reduction in power consumption.

  2. Redox-Linked Conformational Control of Proton Coupled Electron Transfer: Y122 in the Ribonucleotide Reductase β2 Subunit

    PubMed Central

    Offenbacher, Adam R.; Burns, Lori A.; Sherrill, C. David; Barry, Bridgette A.

    2013-01-01

    Tyrosyl radicals play essential roles in biological proton coupled electron transfer (PCET) reactions. Ribonucleotide reductase (RNR) catalyzes the reduction of ribonucleotides and is vital in DNA replication in all organisms. Class Ia RNRs consist of α2 and β2 homodimeric subunits. In class 1a RNR, such as the E. coli enzyme, an essential tyrosyl radical (Y122O•)-diferric cofactor is located in β2. While Y122O• is extremely stable in free β2, Y122O• is highly reactive in the quaternary substrate-α2β2 complex and serves as a radical initiator in catalytic PCET between β2 and α2. In this report, we investigate the structural interactions that control the reactivity of Y122O• in a model system, isolated E. coli β2. Y122O• was reduced with hydroxyurea (HU), a radical scavenger that quenches the radical in a clinically relevant reaction. In the difference FT-IR spectrum, associated with this PCET reaction, amide I (CO) and amide II (CN/NH) bands were observed. Specific 13C-labeling of the tyrosine C1 carbon assigned a component of these bands to the Y122-T123 amide bond. Comparison to density functional calculations on a model dipeptide, tyrosine-threonine, and structural modeling demonstrated that PCET is associated with a Y122 rotation and a 7.2 Å translation of the Y122 phenolic oxygen. To test for the functional consequences of this structural change, a proton inventory defined the origin of the large solvent isotope effect (SIE=16.7±1.0 at 25°C) on this reaction. These data suggest that the one electron, HU-mediated reduction of Y122O• is associated with two, rate-limiting (full or partial) proton transfer reactions. One is attributable to HU oxidation (SIE=11.9, net H atom transfer), and the other is attributable to coupled, hydrogen-bonding changes in the Y122O•-diferric cofactor (SIE=1.4). These results illustrate the importance of redox-linked changes to backbone and ring dihedral angles in high potential PCET and provide evidence for

  3. The Dynamics Behind the Affinity: Controlling Heme-Gas Affinity via Geminate Recombination and Heme Propionate Conformation in the NO Carrier Cytochrome c'.

    PubMed

    Andrew, Colin R; Petrova, Olga N; Lamarre, Isabelle; Lambry, Jean-Christophe; Rappaport, Fabrice; Negrerie, Michel

    2016-11-18

    Nitric oxide (NO) sensors are heme proteins which may also bind CO and O2. Control of heme-gas affinity and their discrimination are achieved by the structural properties and reactivity of the heme and its distal and proximal environments, leading to several energy barriers. In the bacterial NO sensor cytochrome c' from Alcaligenes xylosoxidans (AXCP), the single Leu16Ala distal mutation boosts the affinity for gas ligands by a remarkable 10(6)-10(8)-fold, transforming AXCP from one of the lowest affinity gas binding proteins to one of the highest. Here, we report the dynamics of diatomics after photodissociation from wild type and L16A-AXCP over 12 orders of magnitude in time. For the L16A variant, the picosecond geminate rebinding of both CO and NO appears with an unprecedented 100% yield, and no exit of these ligands from protein to solvent could be observed. Molecular dynamic simulations saliently demonstrate that dissociated CO stays within 4 Å from Fe(2+), in contrast to wild-type AXCP. The L16A mutation confers a heme propionate conformation and docking site which traps the diatomics, maximizing the probability of recombination and directly explaining the ultrahigh affinities for CO, NO, and O2. Overall, our results point to a novel mechanism for modulating heme-gas affinities in proteins.

  4. Machinery Management. FMO: Fundamentals of Machine Operation. Third Edition.

    ERIC Educational Resources Information Center

    Bowers, Wendell

    This text is intended to provide a basic understanding of selecting, maintaining, and managing farm machinery. The following topics are covered in the individual chapters: dealing with typical problems in farm machinery management; measuring machine capacity; improving field efficiency; matching machine size and capacity; estimating power…

  5. Automated Recognition of Advanced Vibration Features for Machinery Fault Classification

    DTIC Science & Technology

    2001-04-05

    fault " using transitional failure data for commercial grade gearboxes . Features will be extracted from accelerometer data obtained on the Mechanical...Machinery Fault Classification DISTRIBUTION: Approved for public release, distribution unlimited This paper is part of the following report: TITLE: New...thru ADP013516 UNCLASSIFIED AUTOMATED RECOGNITION OF ADVANCED VIBRATION FEATURES FOR MACHINERY FAULT CLASSIFICATION Katherine McClintic, Robert Campbell

  6. 46 CFR 109.205 - Inspection of boilers and machinery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ....205 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE DRILLING UNITS OPERATIONS Tests, Drills, and Inspections § 109.205 Inspection of boilers and machinery. The chief engineer or engineer in charge, before he assumes charge of the boilers and machinery of a unit shall inspect...

  7. 46 CFR 109.419 - Report of unsafe machinery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE DRILLING UNITS OPERATIONS Reports, Notifications, and Records Reports and Notifications § 109.419 Report of unsafe machinery. If a boiler, unfired pressure vessel, or other machinery on a unit is unsafe to operate, the master...

  8. 46 CFR 169.315 - Ventilation (other than machinery spaces).

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Ventilation (other than machinery spaces). 169.315 Section 169.315 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS SAILING SCHOOL VESSELS Construction and Arrangement Hull Structure § 169.315 Ventilation (other than machinery spaces). (a) All enclosed spaces within the...

  9. 46 CFR 58.20-15 - Installation of refrigerating machinery.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... refrigerating machinery. (a) Where refrigerating machines are installed in which anhydrous ammonia is used as a... a solution of aqua ammonia and machines using carbon dioxide are exempt from this requirement...) Machinery compartments containing equipment for ammonia shall be fitted with a sprinkler system providing an...

  10. 46 CFR 185.208 - Accidents to machinery.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Accidents to machinery. 185.208 Section 185.208 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS (UNDER 100 GROSS TONS) OPERATIONS Marine Casualties and Voyage Records § 185.208 Accidents to machinery. The owner,...

  11. 46 CFR 185.208 - Accidents to machinery.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Accidents to machinery. 185.208 Section 185.208 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS (UNDER 100 GROSS TONS) OPERATIONS Marine Casualties and Voyage Records § 185.208 Accidents to machinery. The owner,...

  12. 46 CFR 122.208 - Accidents to machinery.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Accidents to machinery. 122.208 Section 122.208 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS CARRYING MORE THAN 150... Voyage Records § 122.208 Accidents to machinery. The owner, managing operator, or master shall...

  13. 46 CFR 78.33-5 - Accidents to machinery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 3 2010-10-01 2010-10-01 false Accidents to machinery. 78.33-5 Section 78.33-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PASSENGER VESSELS OPERATIONS Reports of Accidents, Repairs, and Unsafe Equipment § 78.33-5 Accidents to machinery. (a) In the event of an...

  14. 46 CFR 78.33-5 - Accidents to machinery.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 3 2014-10-01 2014-10-01 false Accidents to machinery. 78.33-5 Section 78.33-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PASSENGER VESSELS OPERATIONS Reports of Accidents, Repairs, and Unsafe Equipment § 78.33-5 Accidents to machinery. (a) In the event of an...

  15. 46 CFR 185.208 - Accidents to machinery.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Accidents to machinery. 185.208 Section 185.208 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS (UNDER 100 GROSS TONS) OPERATIONS Marine Casualties and Voyage Records § 185.208 Accidents to machinery. The owner,...

  16. 46 CFR 78.33-5 - Accidents to machinery.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 3 2013-10-01 2013-10-01 false Accidents to machinery. 78.33-5 Section 78.33-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PASSENGER VESSELS OPERATIONS Reports of Accidents, Repairs, and Unsafe Equipment § 78.33-5 Accidents to machinery. (a) In the event of an...

  17. 46 CFR 122.208 - Accidents to machinery.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Accidents to machinery. 122.208 Section 122.208 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS CARRYING MORE THAN 150... Voyage Records § 122.208 Accidents to machinery. The owner, managing operator, or master shall...

  18. 46 CFR 185.208 - Accidents to machinery.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Accidents to machinery. 185.208 Section 185.208 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS (UNDER 100 GROSS TONS) OPERATIONS Marine Casualties and Voyage Records § 185.208 Accidents to machinery. The owner,...

  19. 46 CFR 78.33-5 - Accidents to machinery.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 3 2011-10-01 2011-10-01 false Accidents to machinery. 78.33-5 Section 78.33-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PASSENGER VESSELS OPERATIONS Reports of Accidents, Repairs, and Unsafe Equipment § 78.33-5 Accidents to machinery. (a) In the event of an...

  20. 46 CFR 122.208 - Accidents to machinery.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 4 2014-10-01 2014-10-01 false Accidents to machinery. 122.208 Section 122.208 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS CARRYING MORE THAN 150... Voyage Records § 122.208 Accidents to machinery. The owner, managing operator, or master shall...

  1. 46 CFR 122.208 - Accidents to machinery.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Accidents to machinery. 122.208 Section 122.208 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS CARRYING MORE THAN 150... Voyage Records § 122.208 Accidents to machinery. The owner, managing operator, or master shall...

  2. 46 CFR 122.208 - Accidents to machinery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Accidents to machinery. 122.208 Section 122.208 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS CARRYING MORE THAN 150... Voyage Records § 122.208 Accidents to machinery. The owner, managing operator, or master shall...

  3. 46 CFR 78.33-5 - Accidents to machinery.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 3 2012-10-01 2012-10-01 false Accidents to machinery. 78.33-5 Section 78.33-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PASSENGER VESSELS OPERATIONS Reports of Accidents, Repairs, and Unsafe Equipment § 78.33-5 Accidents to machinery. (a) In the event of an...

  4. 46 CFR 185.208 - Accidents to machinery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Accidents to machinery. 185.208 Section 185.208 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS (UNDER 100 GROSS TONS) OPERATIONS Marine Casualties and Voyage Records § 185.208 Accidents to machinery. The owner,...

  5. 46 CFR 58.20-15 - Installation of refrigerating machinery.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... refrigerating machinery. (a) Where refrigerating machines are installed in which anhydrous ammonia is used as a... a solution of aqua ammonia and machines using carbon dioxide are exempt from this requirement...) Machinery compartments containing equipment for ammonia shall be fitted with a sprinkler system providing an...

  6. 4. FIRST FLOOR INTERIOR, AMMONIA COMPRESSION DYNAMOS IN MACHINERY ROOM ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. FIRST FLOOR INTERIOR, AMMONIA COMPRESSION DYNAMOS IN MACHINERY ROOM ALONG SOUTH SIDE OF WESTERN PORTION OF BUILDING, FROM EASTERN ENTRANCE TO MACHINERY ROOM, LOOKING WEST. - Oakland Naval Supply Center, Cold Storage Warehouse, South of C Street between First & Second Street, Oakland, Alameda County, CA

  7. 46 CFR 58.20-15 - Installation of refrigerating machinery.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... refrigerating machinery. (a) Where refrigerating machines are installed in which anhydrous ammonia is used as a... a solution of aqua ammonia and machines using carbon dioxide are exempt from this requirement...) Machinery compartments containing equipment for ammonia shall be fitted with a sprinkler system providing an...

  8. Post-stressed concrete foundation may reduce machinery vibration

    NASA Technical Reports Server (NTRS)

    Fistedis, S. H.

    1967-01-01

    Post-stressing concrete mat foundation reduces excessive vibrations in machinery. The mat is stressed in compression after the machinery is mounted, thus closing any cracks in it, altering the distribution of the soil subgrade reaction on the mat, and changing the mat-subgrade natural frequency.

  9. 29 CFR 1910.213 - Woodworking machinery requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 5 2010-07-01 2010-07-01 false Woodworking machinery requirements. 1910.213 Section 1910... Woodworking machinery requirements. (a) Machine construction general. (1) Each machine shall be so constructed... with the specific requirements of § 1910.219. (10) It is recommended that each power-driven...

  10. Machinery Management. FMO: Fundamentals of Machine Operation. Third Edition.

    ERIC Educational Resources Information Center

    Bowers, Wendell

    This text is intended to provide a basic understanding of selecting, maintaining, and managing farm machinery. The following topics are covered in the individual chapters: dealing with typical problems in farm machinery management; measuring machine capacity; improving field efficiency; matching machine size and capacity; estimating power…

  11. 46 CFR 169.315 - Ventilation (other than machinery spaces).

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Ventilation (other than machinery spaces). 169.315... SCHOOL VESSELS Construction and Arrangement Hull Structure § 169.315 Ventilation (other than machinery... provide adequate ventilation in all ordinary weather conditions. Provided that paragraph (a) of...

  12. Oblique view of southeast machinery house, SF 109, with NE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Oblique view of southeast machinery house, SF 109, with NE machinery house in background, at downstream end of lock, view towards north northwest - St. Lucie Canal, St. Lucie Lock No. 1, St. Lucie, Cross State Canal, Okeechobee Intracoastal Waterway, Stuart, Martin County, FL

  13. Responses of chromosome segregation machinery to mechanical perturbations.

    PubMed

    Itabashi, Takeshi; Takagi, Jun; Suzuki, Kazuya; Ishiwata, Shin'ichi

    2013-01-01

    For genome stability, the proper segregation of chromosomes is required. The exquisite process of chromosome segregation has charmed a lot of cell- and molecular biologists into watching what happens inside a mitotic cell and how each molecule contributes to this process for the accomplishment of accurate cell division1. The process to partition the duplicated genome to the daughter cells in each cell division is mediated by a self-organized structure called the mitotic spindle. It is well known that the mitotic spindle is a multi-component macromolecular machine composed of microtubules, molecular motors (kinesins, cytoplasmic dynein), and other regulatory molecules (microtubule-associated proteins, kinases, etc.). In recent years, most of the protein components of the mitotic spindle have been identified and the functions of these proteins have been characterized using molecular perturbations2,3. Thus, the mechanisms for spindle assembly and chromosome segregation are being revealed rapidly. However, the chromosome segregation machinery is poorly understood from the mechanical point of view, such as how the mitotic spindle within a cell responds to a variety of mechanical forces, originating from cell-cell interactions or environmental fluctuations. Recent advances in the controlled mechanical perturbation have indicated that the mitotic spindle possesses a structural pliability, size adaptability to the applied external forces, and a strong self-organizing ability. Mechanical perturbations revealed also the mechanochemical regulation of chromosome segregation machinery, which responds to the applied forces. Here, we discuss the current progress in the biophysical research on the architectural and functional dynamics of the mitotic spindle.

  14. Direct observation of bis(dicarbollyl)nickel conformers in solution by fluorescence spectroscopy: an approach to redox-controlled metallacarborane molecular motors.

    PubMed

    Safronov, Alexander V; Shlyakhtina, Natalia I; Everett, Thomas A; VanGordon, Monika R; Sevryugina, Yulia V; Jalisatgi, Satish S; Hawthorne, M Frederick

    2014-10-06

    As a continuation of work on metallacarborane-based molecular motors, the structures of substituted bis(dicarbollyl)nickel complexes in Ni(III) and Ni(IV) oxidation states were investigated in solution by fluorescence spectroscopy. Symmetrically positioned cage-linked pyrene molecules served as fluorescent probes to enable the observation of mixed meso-trans/dl-gauche (pyrene monomer fluorescence) and dl-cis/dl-gauche (intramolecular pyrene excimer fluorescence with residual monomer fluorescence) cage conformations of the nickelacarboranes in the Ni(III) and Ni(IV) oxidation states, respectively. The absence of energetically disfavored conformers in solution--dl-cis in the case of nickel(III) complexes and meso-trans in the case of nickel(IV)--was demonstrated based on spectroscopic data and conformer energy calculations in solution. The conformational persistence observed in solution indicates that bis(dicarbollyl)nickel complexes may provide attractive templates for building electrically driven and/or photodriven molecular motors.

  15. Conformal Vortex Crystals.

    PubMed

    Menezes, Raí M; Silva, Clécio C de Souza

    2017-10-06

    We investigate theoretically globally nonuniform configurations of quantized-flux vortices in clean superconductors trapped by an external force field that induces a nonuniform vortex density profile. Using an extensive series of numerical simulations, we demonstrate that, for suitable choices of the force field, and bellow a certain transition temperature, the vortex system self-organizes into highly inhomogeneous conformal crystals in a way as to minimize the total energy. These nonuniform structures are topologically ordered and can be mathematically mapped into a triangular Abrikosov lattice via a conformal transformation. Above the crystallization temperature, the conformal vortex crystal becomes unstable and gives place to a nonuniform polycrystalline structure. We propose a simple method to engineer the potential energy profile necessary for the observation of conformal crystals of vortices, which can also be applied to other 2D particle systems, and suggest possible experiments in which conformal or quasi-conformal vortex crystals could be observed in bulk superconductors and in thin films.

  16. Fractionated Conformal Radiotherapy for Management of Optic Nerve Sheath Meningiomas: Long-Term Outcomes of Tumor Control and Visual Function at a Single Institution

    SciTech Connect

    Metellus, Philippe; Kapoor, Sumit; Kharkar, Siddharth; Batra, Sachin; Jackson, Juan F.; Kleinberg, Lawrence; Miller, Neil R.; Rigamonti, Daniele

    2011-05-01

    Purpose: To provide the long-term outcomes of patients treated with fractionated conformal radiotherapy (FCRT) for presumed optic nerve sheath meningiomas (ONSMs). Patients and Methods: Between 1995 and 2002, 9 patients with a presumed ONSM were treated with FCRT at our institution. The indications for FCRT were significant visual dysfunction at presentation, progression of visual dysfunction during a period of observation, tumor growth documented by sequential imaging, or a combination of these findings. In 2 patients, FCRT was performed as adjuvant therapy, and in 7, it was the initial and primary treatment. Results: Of the 9 patients, 6 were women and 3 were men, with a mean age of 47 years. All 9 patients had evidence of optic nerve dysfunction in the affected eye, characterized by reduced visual acuity, a visual field defect, and a relative afferent pupillary defect. In addition, 2 patients had proptosis and 1 had diplopia. The mean follow-up period was 98 {+-} 31.7 months (median, 90; range, 61-151). After FCRT, the visual function improved in the 7 patients who had undergone FCRT as the primary treatment. However, 2 patients who were blind in their affected eye at FCRT remained blind. In 4 of the 7 patients with improvement, the improvement was documented within 1-3 months after FCRT. The tumor control rate was 100%. Proptosis and diplopia also regressed in 100% of patients. At 2 years after FCRT, 1 patient had developed radiation retinopathy. Conclusion: The results of our study have shown that FCRT is a safe and effective treatment of ONSMs, affording satisfactory long-term tumor control, good functional outcome, and low treatment morbidity. FCRT should be considered the treatment of choice for patients with presumed ONSMs for whom the treatment has been deemed appropriate.

  17. Control of IgG LC:HC ratio in stably transfected CHO cells and study of the impact on expression, aggregation, glycosylation and conformational stability.

    PubMed

    Ho, Steven C L; Koh, Esther Y C; van Beers, Miranda; Mueller, Monika; Wan, Corrine; Teo, Gavin; Song, Zhiwei; Tong, Yen Wah; Bardor, Muriel; Yang, Yuansheng

    2013-06-10

    Immunoglobulin G (IgG), the most common class of commercial monoclonal antibodies (mAbs), exists as multimers of two identical light chains (LC) and two identical heavy chains (HC) assembled together by disulfide bridges. Due to the kinetics of mAb assembly, it is suggested that expression of LC and HC in equal amounts is not optimal for IgG production. We designed a set of vectors using internal ribosome entry site (IRES) elements to control LC and HC expression. The intracellular LC:HC ratio of stable IgG expressing Chinese hamster ovary (CHO) cell pools can be controlled effectively at four different ratios of 3.43, 1.24, 1.12, and 0.32. The stable pools were used to study the impact of LC:HC ratio on mAb expression and quality. Gene amplification was most effective for pools with excess LC and generated the highest mAb titers among the transfected pools. When LC:HC ratio was greater than one, more than 97% of the secreted products were IgG monomers. The products also have similar N-glycosylation profiles and conformational stabilities at those ratios. For pools presented a lower LC:HC ratio of 0.32, monomers only constituted half of the product with the other half being aggregates and mAb fragments. High mannose-type N-glycans increased while fucosylated and galactosylated glycans decreased significantly at the lowest LC:HC ratio. Product stability was also adversely affected. The results obtained provide insights to the impact of different LC:HC ratios on stable mAb production and useful information for vector design during generation of mAb producing cell lines. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. The Conformal Bootstrap

    NASA Astrophysics Data System (ADS)

    Simmons-Duffin, David

    These notes are from courses given at TASI and the Advanced Strings School in summer 2015. Starting from principles of quantum field theory and the assumption of a traceless stress tensor, we develop the basics of conformal field theory, including conformal Ward identities, radial quantization, reection positivity, the operator product expansion, and conformal blocks. We end with an introduction to numerical bootstrap methods, focusing on the 2d and 3d Ising models.

  19. Imaging of conformational changes

    SciTech Connect

    Michl, Josef

    2016-03-13

    Control of intramolecular conformational change in a small number of molecules or even a single one by an application of an outside electric field defined by potentials on nearby metal or dielectric surfaces has potential applications in both 3-D and 2-D nanotechnology. Specifically, the synthesis, characterization, and understanding of designed solids with controlled built-in internal rotational motion of a dipole promises a new class of materials with intrinsic dielectric, ferroelectric, optical and optoelectronic properties not found in nature. Controlled rotational motion is of great interest due to its expected utility in phenomena as diverse as transport, current flow in molecular junctions, diffusion in microfluidic channels, and rotary motion in molecular machines. A direct time-resolved observation of the dynamics of motion on ps or ns time scale in a single molecule would be highly interesting but is also very difficult and has yet to be accomplished. Much can be learned from an easier but still challenging comparison of directly observed initial and final orientational states of a single molecule, which is the basis of this project. The project also impacts the understanding of surface-enhanced Raman spectroscopy (SERS) and single-molecule spectroscopic detection, as well as the synthesis of solid-state materials with tailored properties from designed precursors.

  20. Controlling the Conformational Energy of a Phenyl Group by Tuning the Strength of a Nonclassical CH···O Hydrogen Bond: The Case of 5-Phenyl-1,3-dioxane.

    PubMed

    Bailey, William F; Lambert, Kyle M; Stempel, Zachary D; Wiberg, Kenneth B; Mercado, Brandon Q

    2016-12-16

    Anancomeric 5-phenyl-1,3-dioxanes provide a unique opportunity to study factors that control conformation. Whereas one might expect an axial phenyl group at C(5) of 1,3-dioxane to adopt a conformation similar to that in axial phenylcyclohexane, a series of studies including X-ray crystallography, NOE measurements, and DFT calculations demonstrate that the phenyl prefers to lie over the dioxane ring in order to position an ortho-hydrogen to participate in a stabilizing, nonclassical CH···O hydrogen bond with a ring oxygen of the dioxane. Acid-catalyzed equilibration of a series of anancomeric 2-tert-butyl-5-aryl-1,3-dioxane isomers demonstrates that remote substituents on the phenyl ring affect the conformational energy of a 5-aryl-1,3-dioxane: electron-withdrawing substituents decrease the conformational energy of the aryl group, while electron-donating substituents increase the conformational energy of the group. This effect is correlated in a very linear way to Hammett substituent parameters. In short, the strength of the CH···O hydrogen bond may be tuned in a predictable way in response to the electron-withdrawing or electron-donating ability of substituents positioned remotely on the aryl ring. This effect may be profound: a 3,5-bis-CF3 phenyl group at C(5) in 1,3-dioxane displays a pronounced preference for the axial orientation. The results are relevant to broader conformational issues involving heterocyclic systems bearing aryl substituents.

  1. Global Design Optimization for Fluid Machinery Applications

    NASA Technical Reports Server (NTRS)

    Shyy, Wei; Papila, Nilay; Tucker, Kevin; Vaidyanathan, Raj; Griffin, Lisa

    2000-01-01

    Recent experiences in utilizing the global optimization methodology, based on polynomial and neural network techniques for fluid machinery design are summarized. Global optimization methods can utilize the information collected from various sources and by different tools. These methods offer multi-criterion optimization, handle the existence of multiple design points and trade-offs via insight into the entire design space can easily perform tasks in parallel, and are often effective in filtering the noise intrinsic to numerical and experimental data. Another advantage is that these methods do not need to calculate the sensitivity of each design variable locally. However, a successful application of the global optimization method needs to address issues related to data requirements with an increase in the number of design variables and methods for predicting the model performance. Examples of applications selected from rocket propulsion components including a supersonic turbine and an injector element and a turbulent flow diffuser are used to illustrate the usefulness of the global optimization method.

  2. Entropy-Driven Conformational Control of α,ω-Difunctional Bidentate-Dithiol Azo-Based Adsorbates Enables the Fabrication of Thermally Stable Surface-Grafted Polymer Films.

    PubMed

    Lee, Han Ju; Jamison, Andrew C; Lee, T Randall

    2016-06-22

    Thermally stable radical initiator monolayers were prepared from uniquely designed α,ω-difunctional adsorbates with bidentate headgroups for the growth of nanoscale polymer films on metal surfaces. The length of the spacer separating the bidentate headgroups was varied to afford 4,4'-(diazene-1,2-diyl)bis(N-(16-(3,5-bis(mercaptomethyl)phenoxy)hexadecyl)-4-cyanopentanamide) (B16), 4,4'-(diazene-1,2-diyl)bis(N-(16-(3,5-bis(mercapto-methyl)phenoxy)decyl)-4-cyanopentanamide) (B10), and 4,4'-(diazene-1,2-diyl)bis(N-(4-(3,5-bis(mercaptomethyl)phenoxy)butyl)-4-cyanopentanamide) (B4). The structural features of the self-assembled monolayers (SAMs) derived from B16, B10, and B4 were characterized by X-ray photoelectron spectroscopy (XPS), ellipsometry, and polarization modulation infrared reflection-absorption spectroscopy (PM-IRRAS) and compared to those derived from an analogous α,ω-difunctional adsorbate with monodentate headgroups, 4,4'-(diazene-1,2-diyl)bis(4-cyano-N-(16-mercaptohexadecyl)pentanamide (M). These studies demonstrate that the conformation (i.e., hairpin vs standing up) of the bidentate initiator adsorbates on gold surfaces was easily controlled by adjusting the concentration of the adsorbates in solution. The results of solution-phase thermal desorption tests revealed that the radical initiator monolayers generated from B16, B10, and B4 exhibit an enhanced thermal stability when compared to those generated from M. Furthermore, a study of the growth of polymer films was performed to evaluate the utility of these new bidentate adsorbate SAMs as film-development platforms for new functional materials and devices. Specifically, surface-grafted polystyrene films were successfully generated from SAMs derived from B16. In contrast, attempts to grow polystyrene films from SAMs derived from M under a variety of analogous conditions were unsuccessful.

  3. Conformations of Substituted Ethanes.

    ERIC Educational Resources Information Center

    Kingsbury, Charles A.

    1979-01-01

    Reviews state-of-the-art of conformational analysis and factors which affect it. Emphasizes sp-3 hybridized acrylic molecules. Provides examples on the importance of certain factors in determining conformation. Purpose, is to provide examples for examination questions. (Author/SA)

  4. Conformal differential invariants

    NASA Astrophysics Data System (ADS)

    Kruglikov, Boris

    2017-03-01

    We compute the Hilbert polynomial and the Poincaré function counting the number of fixed jet-order differential invariants of conformal metric structures modulo local diffeomorphisms, and we describe the field of rational differential invariants separating generic orbits of the diffeomorphism pseudogroup action. This resolves the local recognition problem for conformal structures.

  5. Conformations of Substituted Ethanes.

    ERIC Educational Resources Information Center

    Kingsbury, Charles A.

    1979-01-01

    Reviews state-of-the-art of conformational analysis and factors which affect it. Emphasizes sp-3 hybridized acrylic molecules. Provides examples on the importance of certain factors in determining conformation. Purpose, is to provide examples for examination questions. (Author/SA)

  6. CONSENSUS AND CONFORMITY.

    ERIC Educational Resources Information Center

    ALLEN, VERNON L.; LEVINE, JOHN M.

    IN THIS STUDY, PROFESSOR ALLEN EMPLOYS TWO METHODS OF BREAKING GROUP CONSENSUS, AND HE MEASURES THE EFFECTS ON THE RESPONSES OF COLLEGE SUBJECTS TO BOTH OBJECTIVE AND SUBJECTIVE STIMULI. THE RESULTS SUGGEST THE NEED FOR MODIFICATION OF EXISTING THEORIES OF CONFORMITY BEHAVIOR. IN ADDITION, THESE RESULTS EMPHASIZE THE DIFFERENCES IN CONFORMITY OF…

  7. Analysis and Control of Vibrational Power Transmission to Machinery Supporting Structures Subjected to a Multi-Excitation System, Part i: Driving Point Mobility Matrix of Beams and Rectangular Plates

    NASA Astrophysics Data System (ADS)

    Koh, Y. K.; White, R. G.

    1996-10-01

    The analysis and control of vibration transmission from a machine source to flexible beam- and plate-like supporting structures via the translational and rotational motions as well as the coupling between these motions are studied in these three companions papers. In these studies, co-located simultaneously acting sinusoidal force and moment excitations are assumed to act on the flexible supporting structures and the transmission of vibrational energy into the structures is expressed in terms of the time-averaged vibrational power. The driving point mobility functions of uniform beams and rectangular plates are derived in the first paper. The existence and contribution of the coupling mobility functions in the case of a multi-excitation system give rise to cancellation of vibrational power components. This observation forms the basis of the proposed vibration control technique, which is studied in the second paper. The experimental arrangements for validation of the cancellation of vibrational power components and the proposed vibration control technique with suitably designed force moment seatings are described in the third paper. The proposed vibration control technique is most suitable for the case of a low to medium constant speed machine mounted on a flexible supporting structure.

  8. Conformity index: a review.

    PubMed

    Feuvret, Loïc; Noël, Georges; Mazeron, Jean-Jacques; Bey, Pierre

    2006-02-01

    We present a critical analysis of the conformity indices described in the literature and an evaluation of their field of application. Three-dimensional conformal radiotherapy, with or without intensity modulation, is based on medical imaging techniques, three-dimensional dosimetry software, compression accessories, and verification procedures. It consists of delineating target volumes and critical healthy tissues to select the best combination of beams. This approach allows better adaptation of the isodose to the tumor volume, while limiting irradiation of healthy tissues. Tools must be developed to evaluate the quality of proposed treatment plans. Dosimetry software provides the dose distribution in each CT section and dose-volume histograms without really indicating the degree of conformity. The conformity index is a complementary tool that attributes a score to a treatment plan or that can compare several treatment plans for the same patient. The future of conformal index in everyday practice therefore remains unclear.

  9. Conformity index: A review

    SciTech Connect

    Feuvret, Loic . E-mail: loic.feuvret@cpo.curie.net; Noel, Georges; Mazeron, Jean-Jacques; Bey, Pierre

    2006-02-01

    We present a critical analysis of the conformity indices described in the literature and an evaluation of their field of application. Three-dimensional conformal radiotherapy, with or without intensity modulation, is based on medical imaging techniques, three-dimensional dosimetry software, compression accessories, and verification procedures. It consists of delineating target volumes and critical healthy tissues to select the best combination of beams. This approach allows better adaptation of the isodose to the tumor volume, while limiting irradiation of healthy tissues. Tools must be developed to evaluate the quality of proposed treatment plans. Dosimetry software provides the dose distribution in each CT section and dose-volume histograms without really indicating the degree of conformity. The conformity index is a complementary tool that attributes a score to a treatment plan or that can compare several treatment plans for the same patient. The future of conformal index in everyday practice therefore remains unclear.

  10. Spiral pocketing by conformal mappings

    NASA Astrophysics Data System (ADS)

    Romero-Carrillo, P.; Dorado, R.; Diaz-Garrido, F. A.; Lopez-Garcia, R.

    2012-04-01

    Pocketing is usual in numerical control (NC) machining applications like die and mould operations. The usual parallel cuts or offset curves strategies show C1 discontinuities, thus they are not well fitted for high speed machining. In order to alleviate this drawback, we propose a C∝. path that fills a target region and it is computed via a conformal mapping of an Archimedes' spiral. Regarding continuity, machining time and overcut, our spirals are adequate if they are compared to CAM system strategies.

  11. Protein Conformational Switches: From Nature to Design

    PubMed Central

    Ha, Jeung-Hoi

    2012-01-01

    Protein conformational switches alter their shape upon receiving an input signal, such as ligand binding, chemical modification, or change in environment. The apparent simplicity of this transformation—which can be carried out by a molecule as small as a thousand atoms or so—belies its critical importance to the life of the cell as well as its capacity for engineering by humans. In the realm of molecular switches, proteins are unique because they are capable of performing a variety of biological functions. Switchable proteins are therefore of high interest to the fields of biology, bio-technology, and medicine. These molecules are beginning to be exploited as the core machinery behind a new generation of biosensors, functionally regulated enzymes, and “smart” biomaterials that react to their surroundings. As inspirations for these designs, researchers continue to analyze existing examples of allosteric proteins. Recent years have also witnessed the development of new methodologies for introducing conformational change into proteins that previously had none. Herein we review examples of both natural and engineered protein switches in the context of four basic modes of conformational change: rigid-body domain movement, limited structural rearrangement, global fold switching, and folding–unfolding. Our purpose is to highlight examples that can potentially serve as platforms for the design of custom switches. Accordingly, we focus on inducible conformational changes that are substantial enough to produce a functional response (e.g., in a second protein to which it is fused), yet are relatively simple, structurally well-characterized, and amenable to protein engineering efforts. PMID:22688954

  12. Failure of RQC machinery causes protein aggregation and proteotoxic stress.

    PubMed

    Choe, Young-Jun; Park, Sae-Hun; Hassemer, Timm; Körner, Roman; Vincenz-Donnelly, Lisa; Hayer-Hartl, Manajit; Hartl, F Ulrich

    2016-03-10

    Translation of messenger RNAs lacking a stop codon results in the addition of a carboxy-terminal poly-lysine tract to the nascent polypeptide, causing ribosome stalling. Non-stop proteins and other stalled nascent chains are recognized by the ribosome quality control (RQC) machinery and targeted for proteasomal degradation. Failure of this process leads to neurodegeneration by unknown mechanisms. Here we show that deletion of the E3 ubiquitin ligase Ltn1p in yeast, a key RQC component, causes stalled proteins to form detergent-resistant aggregates and inclusions. Aggregation is dependent on a C-terminal alanine/threonine tail that is added to stalled polypeptides by the RQC component, Rqc2p. Formation of inclusions additionally requires the poly-lysine tract present in non-stop proteins. The aggregates sequester multiple cytosolic chaperones and thereby interfere with general protein quality control pathways. These findings can explain the proteotoxicity of ribosome-stalled polypeptides and demonstrate the essential role of the RQC in maintaining proteostasis.

  13. 62. VIEW SHOWING INSTALLATION TAINTER VALVE MACHINERY MONOLITH NO. 321, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    62. VIEW SHOWING INSTALLATION TAINTER VALVE MACHINERY MONOLITH NO. 32-1, LOOKING WEST Photograph No. 8571. October 24, 1949 - Upper Mississippi River 9-Foot Channel Project, Lock & Dam 27, Granite City, Madison County, IL

  14. 36. DETAILS FOR SCREENING MACHINERY, DEER ISLAND PUMPING STATION, METROPOLITAN ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    36. DETAILS FOR SCREENING MACHINERY, DEER ISLAND PUMPING STATION, METROPOLITAN WATER AND SEWERAGE BOARD, METROPOLITAN SEWERAGE WORKS, DECEMBER 1909. Aperture card 6611-1 - Deer Island Pumping Station, Boston, Suffolk County, MA

  15. 46. Interior detail of barge crane engine house with machinery. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    46. Interior detail of barge crane engine house with machinery. Lambert Hoisting Engine Company Winder Powered by A Gray Marine Diesel. - Barbour Boat Works, Tryon Palace Drive, New Bern, Craven County, NC

  16. 95. PHOTOCOPY OF DRAWING, SPAN 1, DETAILS OF TURNTABLE MACHINERY, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    95. PHOTOCOPY OF DRAWING, SPAN 1, DETAILS OF TURNTABLE MACHINERY, 3/4' and 1 1/2' = 1' (CENTER CONE, RADIAL STRUT RING, TRACK, ROLLERS, PINION GEARS) - Keokuk & Hamilton Bridge, Spanning Mississippi River, Keokuk, Lee County, IA

  17. 87. DAM TAINTER GATE OPERATING MACHINERY TRAVELING HOIST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    87. DAM - TAINTER GATE OPERATING MACHINERY - TRAVELING HOIST - AMERICAN TYPE ASSEMBLY (ML-5-55/111-FS), February 1938 - Upper Mississippi River 9-Foot Channel Project, Lock & Dam No. 5, Minneiska, Winona County, MN

  18. 86. DAM TAINTER GATE OPERATING MACHINERY HOIST CAR ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    86. DAM - TAINTER GATE OPERATING MACHINERY - HOIST CAR NO. 2 - ELECTRIFICATION HOIST CLUTCH MODIFICATION (ML-5-55/6), March 1956 - Upper Mississippi River 9-Foot Channel Project, Lock & Dam No. 5, Minneiska, Winona County, MN

  19. 5. INTERIOR, FIRST FLOOR, WEST VIEW OF MACHINERY FRAME, SHOWING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. INTERIOR, FIRST FLOOR, WEST VIEW OF MACHINERY FRAME, SHOWING MAIN VERTICAL SHAFT WITH CAST-IRON WALLOWER GEAR AT LOWER END, AND THE GREAT SPUR WHEEL OF ALL WOODEN CONSTRUCTION - Robeson-Williams Grist Mill, Roslyn, Nassau County, NY

  20. 7. Detail, machinery shed atop east portal of Tunnel 28, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. Detail, machinery shed atop east portal of Tunnel 28, showing shaft and pulley system, 210mm lens with electronic flash fill. - Central Pacific Transcontinental Railroad, Tunnel No. 28, Milepost 134.75, Applegate, Placer County, CA

  1. 101. STARBOARD AIRPLANE ELEVATOR MACHINERY ROOM AFT LOOKING FORWARD ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    101. STARBOARD AIRPLANE ELEVATOR MACHINERY ROOM - AFT LOOKING FORWARD PORT TO STARBOARD SHOWING ELEVATOR ENGINE, LIFTING WIRES, HYDRAULIC PIPING WITH REMOTE OPERATOR. - U.S.S. HORNET, Puget Sound Naval Shipyard, Sinclair Inlet, Bremerton, Kitsap County, WA

  2. 26. DETAIL OF HEADGATE HOIST MACHINERY, TWIN FALLS MAIN CANAL. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    26. DETAIL OF HEADGATE HOIST MACHINERY, TWIN FALLS MAIN CANAL. - Milner Dam & Main Canal: Twin Falls Canal Company, On Snake River, 11 miles West of city of Burley, Idaho, Twin Falls, Twin Falls County, ID

  3. 28. View of operating machinery shoeing electric motor, clutch drive ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    28. View of operating machinery shoeing electric motor, clutch drive wheel and hand-painted alignment dial, (Nov. 25, 1988) - University Heights Bridge, Spanning Harlem River at 207th Street & West Harlem Road, New York County, NY

  4. 7. Interior view of machinery looking at window of east ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. Interior view of machinery looking at window of east wall of 1953 addition, view to northeast. - Ellsworth Air Force Base, Waste Water Treatment Plant, Ellsworth Street, Blackhawk, Meade County, SD

  5. 14. MACHINERY DETAILS: CENTER WHEEL FRAME AND AXEL, JACK WHEEL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    14. MACHINERY DETAILS: CENTER WHEEL FRAME AND AXEL, JACK WHEEL FRAME, JACK NUT HOUSING, JACK NUT, ETC. - Niantic River Swing Bridge, Spanning Niantic River between East Lyme & Waterford, Old Lyme, New London County, CT

  6. 6. Interior view of mechanical room; showing machinery; on recessed ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. Interior view of mechanical room; showing machinery; on recessed floor level of west wing, near main entrance, view to southwest. - Ellsworth Air Force Base, Administration Office, 2704 George Drive, Blackhawk, Meade County, SD

  7. Powerhouse east, north and west elevations and operating machinery, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Powerhouse - east, north and west elevations and operating machinery, battery storage building, and typical span of steel service bridge - Grand Valley Diversion Dam, Half a mile north of intersection of I-70 & Colorado State Route 65, Cameo, Mesa County, CO

  8. STEAMING OF MACHINERY FOR OPENING AND CLOSING OF LOCK GATES ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    STEAMING OF MACHINERY FOR OPENING AND CLOSING OF LOCK GATES TO PREVENT FREEZING UP - U.S. Coast Guard Icebreaker Mackinaw, Icebreaker Mackinaw Maritime Museum 131 South Huron Avenue, Mackinaw City, Cheboygan County, MI

  9. 21. Detail of remains of machinery house viewed from below ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    21. Detail of remains of machinery house viewed from below anchor-span deck, showing drawspan cable running back to the winding drum of the winch; view to northeast. - Summer Street Bridge, Spanning Reserved Channel, Boston, Suffolk County, MA

  10. 51. FIRST FLOOR INTERIOR VIEW TO SOUTHEAST: Winding machinery to ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    51. FIRST FLOOR INTERIOR VIEW TO SOUTHEAST: Winding machinery to right, and belt-driven machine tools to left. Museum mezzanine in upper portion of photo. - San Francisco Cable Railway, Washington & Mason Streets, San Francisco, San Francisco County, CA

  11. 16. DETAIL VIEW OF AUXILIARY LOCK MITER GATE OPERATING MACHINERY ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    16. DETAIL VIEW OF AUXILIARY LOCK MITER GATE OPERATING MACHINERY LOCATED IN INTERMEDIATE WALL, LOOKING NORTHWEST - Upper Mississippi River 9-Foot Channel Project, Lock & Dam 27, Granite City, Madison County, IL

  12. 17. VIEW, LOOKING WEST, SHOWING BRIDGE MACHINERY HOUSE ON FIXED ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    17. VIEW, LOOKING WEST, SHOWING BRIDGE MACHINERY HOUSE ON FIXED SPAN - New York, New Haven & Hartford Railroad, Groton Bridge, Spanning Thames River between New London & Groton, New London, New London County, CT

  13. 20. DETAIL VIEW OF MOVABLE SPAN MACHINERY UNDER GRID DECK ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    20. DETAIL VIEW OF MOVABLE SPAN MACHINERY UNDER GRID DECK AT CENTRAL CONCRETE SUPPORT PEDESTAL, SHOWING DRIVE GEARS, ELECTRIC MOTOR AND STEEL BEAMS (taken in January 1984) - Sharptown Bridge, Spanning Nanticoke River, State Route 313, Sharptown, Wicomico County, MD

  14. 15. MACHINERY DETAILS: LATCH WHEEL BRACKET, LATCH POCKET, LOCK BAR, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    15. MACHINERY DETAILS: LATCH WHEEL BRACKET, LATCH POCKET, LOCK BAR, LATCH CRADLE, SPLIT COLLAR, ETC. - Niantic River Swing Bridge, Spanning Niantic River between East Lyme & Waterford, Old Lyme, New London County, CT

  15. 18. INTERIOR VIEW OF THE GENERATOR HOUSE, SHOWING CONCRETE MACHINERY ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    18. INTERIOR VIEW OF THE GENERATOR HOUSE, SHOWING CONCRETE MACHINERY FOOTINGS, LOOKING SOUTHWEST. - Tower Hill No. 2 Mine, Approximately 0.47 mile Southwest of intersection of Stone Church Road & Township Route 561, Hibbs, Fayette County, PA

  16. 14. Overview of bay without sluice gate machinery to northeast ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    14. Overview of bay without sluice gate machinery to northeast - Mississippi River 9-Foot Channel, Lock & Dam No. 1, In Mississippi River at Mississippi Boulevard, below Ford Parkway Bridge, Saint Paul, Ramsey County, MN

  17. 8. MACHINERY SHED STORAGE ROOM ADDITION DETAIL SHOWING MATRIX OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    8. MACHINERY SHED STORAGE ROOM ADDITION DETAIL SHOWING MATRIX OF NAILS USED TO ADHERE PORTLAND CEMENT PLASTER, SOUTH ADOBE WALL ADJACENT TO WINDOW Note: Photographs Nos. AZ-159-A-9 through AZ-159-A-10 are photocopies of photographs. The original prints and negatives are located in the SCS Tucson Plant Materials Center, Tucson, Arizona. Photographer Ted F. Spaller. - Tucson Plant Material Center, Machinery Shed, 3241 North Romero Road, Tucson, Pima County, AZ

  18. 65. CALIFORNIA STREET CABLE RAILWAY WINDING MACHINERY: Photocopy of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    65. CALIFORNIA STREET CABLE RAILWAY - WINDING MACHINERY: Photocopy of February 1955 photograph showing the winding machinery of the California Street Cable Railroad. The two suspended sheaves on the right of the photograph bore down on the cable as it left the winders, supplying tension to the cable and eliminating the need for a long tension run. - San Francisco Cable Railway, Washington & Mason Streets, San Francisco, San Francisco County, CA

  19. Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells

    DTIC Science & Technology

    2016-10-01

    AWARD NUMBER: W81XWH-15-1-0644 TITLE: Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells PRINCIPAL INVESTIGATOR: Chun-Ju...Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0644 5c. PROGRAM ELEMENT...Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Cancer stem cells (CSCs), a cell population with acquired perpetuating self-renewal properties

  20. Evolution and diversification of the basal transcription machinery.

    PubMed

    Duttke, Sascha H C

    2015-03-01

    Transcription initiation was once thought to be regulated primarily by sequence-specific transcription factors with the basal transcription machinery being largely invariant. Gradually it became apparent that the basal transcription machinery greatly diversified during evolution and new studies now demonstrate that diversification of the TATA-binding protein (TBP) family yielded specialized and largely independent transcription systems. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Precision optical angular position marker system for rotating machinery

    NASA Technical Reports Server (NTRS)

    Barranger, J. P.

    1983-01-01

    An optical system is described which generates one or more markers of the angular shaft position of rotating machinery. The system consists of a light source, an optical cable, a machinery mounted lens assembly, a light detector, and a signal conditioner. Light reflected by targets on the rotor is converted to a digital output signal. The system is highly immune to extreme environments of vibration and temperature and achieved a 0.002 percent precision under operational test conditions.

  2. EC declaration of conformity.

    PubMed

    Donawa, M E

    1996-05-01

    The CE-marking procedure requires that manufacturers draw up a written declaration of conformity before placing their products on the market. However, some companies do not realize that this is a requirement for all devices. Also, there is no detailed information concerning the contents and format of the EC declaration of conformity in the medical device Directives or in EC guidance documentation. This article will discuss some important aspects of the EC declaration of conformity and some of the guidance that is available on its contents and format.

  3. Γ-conformal algebras

    NASA Astrophysics Data System (ADS)

    Golenishcheva-Kutuzova, Maria I.; Kac, Victor G.

    1998-04-01

    Γ-conformal algebra is an axiomatic description of the operator product expansion of chiral fields with simple poles at finitely many points. We classify these algebras and their representations in terms of Lie algebras and their representations with an action of the group Γ. To every Γ-conformal algebra and a character of Γ we associate a Lie algebra generated by fields with the OPE with simple poles. Examples include twisted affine Kac-Moody algebras, the sin algebra (which is a "Γ-conformal" analogue of the general linear algebra) and its analogues, the algebra of pseudodifferential operators on the circle, etc.

  4. Conformal Carroll groups

    NASA Astrophysics Data System (ADS)

    Duval, C.; Gibbons, G. W.; Horvathy, P. A.

    2014-08-01

    Conformal extensions of Lévy-Leblond's Carroll group, based on geometric properties analogous to those of Newton-Cartan space-time are proposed. The extensions are labeled by an integer k. This framework includes and extends our recent study of the Bondi-Metzner-Sachs (BMS) and Newman-Unti (NU) groups. The relation to conformal Galilei groups is clarified. Conformal Carroll symmetry is illustrated by ‘Carrollian photons’. Motion both in the Newton-Cartan and Carroll spaces may be related to that of strings in the Bargmann space.

  5. Dynamic Model Exposes the Energetics and Dynamics of the Injection Machinery for Bacteriophage T4.

    PubMed

    Maghsoodi, Ameneh; Chatterjee, Anupam; Andricioaei, Ioan; Perkins, Noel C

    2017-07-11

    Bacteriophage T4 infects the bacterial host (Escherichia coli) using an efficient genomic delivery machine that is driven by elastic energy stored in a contractile tail sheath. Although the atomic structure of T4 is largely known, the dynamics of its fascinating injection machinery is not understood. This article contributes, to our knowledge, the first predictions of the energetics and dynamics of the T4 injection machinery using a novel dynamic model. The model employs an atomistic (molecular dynamics) representation of a fraction of the sheath structure to generate a continuum model of the entire sheath that also couples to a model of the viral capsid and tail tube. The resulting model of the entire injection machine reveals estimates for the energetics, timescale, and pathway of the T4 injection process as well as the force available for cell rupture. It also reveals the large and highly nonlinear conformational changes of the sheath whose elastic energy drives the injection process. Copyright © 2017 Biophysical Society. All rights reserved.

  6. A Histidine Residue of the Influenza Virus Hemagglutinin Controls the pH Dependence of the Conformational Change Mediating Membrane Fusion

    PubMed Central

    Mair, Caroline M.; Meyer, Tim; Schneider, Katjana; Huang, Qiang; Veit, Michael

    2014-01-01

    ABSTRACT The conformational change of the influenza virus hemagglutinin (HA) protein mediating the fusion between the virus envelope and the endosomal membrane was hypothesized to be induced by protonation of specific histidine residues since their pKas match the pHs of late endosomes (pKa of ∼6.0). However, such critical key histidine residues remain to be identified. We investigated the highly conserved His184 at the HA1-HA1 interface and His110 at the HA1-HA2 interface of highly pathogenic H5N1 HA as potential pH sensors. By replacing both histidines with different amino acids and analyzing the effect of these mutations on conformational change and fusion, we found that His184, but not His110, plays an essential role in the pH dependence of the conformational change of HA. Computational modeling of the protonated His184 revealed that His184 is central in a conserved interaction network possibly regulating the pH dependence of conformational change via its pKa. As the propensity of histidine to get protonated largely depends on its local environment, mutation of residues in the vicinity of histidine may affect its pKa. The HA of highly pathogenic H5N1 viruses carries a Glu-to-Arg mutation at position 216 close to His184. By mutation of residue 216 in the highly pathogenic as well as the low pathogenic H5 HA, we observed a significant influence on the pH dependence of conformational change and fusion. These results are in support of a pKa-modulating effect of neighboring residues. IMPORTANCE The main pathogenic determinant of influenza viruses, the hemagglutinin (HA) protein, triggers a key step of the infection process: the fusion of the virus envelope with the endosomal membrane releasing the viral genome. Whereas essential aspects of the fusion-inducing mechanism of HA at low pH are well understood, the molecular trigger of the pH-dependent conformational change inducing fusion has been unclear. We provide evidence that His184 regulates the pH dependence of

  7. Conformational Electroresistance and Hysteresis in Nanoclusters

    SciTech Connect

    Li, Xiangguo; Zhang, Xiaoguang; Cheng, Hai-Ping

    2014-07-02

    Among many mechanisms proposed for electroresistance, ones involving structural changes are the least understood because of challenges of controllability and repeatability. Yet structural changes can cause dramatic changes in electronic properties, leading to multiple ways in which conduction paths can be opened and closed, not limited to filament movement or variation in molecular conductance. Here we show at least another way: conformational dependence of the Coulomb charging energy of a nanocluster, where charging induced conformational distortion changes the blockade voltage, which in turn leads to a giant electroresistance. This intricate interplay between charging and conformation change is demonstrated in a nanocluster Zn3O4 by combining a first-principles calculation with a temperature dependent transport model. The predicted hysteretic Coulomb blockade staircase in the current-voltage curve adds another dimension to the rich phenomenon of tunneling electroresistance. The new mechanism also provides a better controlled and repeatable platform to study conformational electroresistance.

  8. Conformational Electroresistance and Hysteresis in Nanoclusters

    DOE PAGES

    Li, Xiangguo; Zhang, Xiaoguang; Cheng, Hai-Ping

    2014-07-02

    Among many mechanisms proposed for electroresistance, ones involving structural changes are the least understood because of challenges of controllability and repeatability. Yet structural changes can cause dramatic changes in electronic properties, leading to multiple ways in which conduction paths can be opened and closed, not limited to filament movement or variation in molecular conductance. Here we show at least another way: conformational dependence of the Coulomb charging energy of a nanocluster, where charging induced conformational distortion changes the blockade voltage, which in turn leads to a giant electroresistance. This intricate interplay between charging and conformation change is demonstrated in amore » nanocluster Zn3O4 by combining a first-principles calculation with a temperature dependent transport model. The predicted hysteretic Coulomb blockade staircase in the current-voltage curve adds another dimension to the rich phenomenon of tunneling electroresistance. The new mechanism also provides a better controlled and repeatable platform to study conformational electroresistance.« less

  9. Animal culture: chimpanzee conformity?

    PubMed

    van Schaik, Carel P

    2012-05-22

    Culture-like phenomena in wild animals have received much attention, but how good is the evidence and how similar are they to human culture? New data on chimpanzees suggest their culture may even have an element of conformity.

  10. Assemblies of Conformal Tanks

    NASA Technical Reports Server (NTRS)

    DeLay, Tom

    2009-01-01

    Assemblies of tanks having shapes that conform to each other and/or conform to other proximate objects have been investigated for use in storing fuels and oxidizers in small available spaces in upper stages of spacecraft. Such assemblies might also prove useful in aircraft, automobiles, boats, and other terrestrial vehicles in which space available for tanks is limited. The basic concept of using conformal tanks to maximize the utilization of limited space is not new in itself: for example, conformal tanks are used in some automobiles to store windshield -washer liquid and coolant that overflows from radiators. The novelty of the present development lies in the concept of an assembly of smaller conformal tanks, as distinguished from a single larger conformal tank. In an assembly of smaller tanks, it would be possible to store different liquids in different tanks. Even if the same liquid were stored in all the tanks, the assembly would offer an advantage by reducing the mechanical disturbance caused by sloshing of fuel in a single larger tank: indeed, the requirement to reduce sloshing is critical in some applications. The figure shows a prototype assembly of conformal tanks. Each tank was fabricated by (1) copper plating a wax tank mandrel to form a liner and (2) wrapping and curing layers of graphite/epoxy composite to form a shell supporting the liner. In this case, the conformal tank surfaces are flat ones where they come in contact with the adjacent tanks. A band of fibers around the outside binds the tanks together tightly in the assembly, which has a quasi-toroidal shape. For proper functioning, it would be necessary to maintain equal pressure in all the tanks.

  11. Conformational sampling techniques.

    PubMed

    Hatfield, Marcus P D; Lovas, Sándor

    2014-01-01

    The potential energy hyper-surface of a protein relates the potential energy of the protein to its conformational space. This surface is useful in determining the native conformation of a protein or in examining a statistical-mechanical ensemble of structures (canonical ensemble). In determining the potential energy hyper-surface of a protein three aspects must be considered; reducing the degrees of freedom, a method to determine the energy of each conformation and a method to sample the conformational space. For reducing the degrees of freedom the choice of solvent, coarse graining, constraining degrees of freedom and periodic boundary conditions are discussed. The use of quantum mechanics versus molecular mechanics and the choice of force fields are also discussed, as well as the sampling of the conformational space through deterministic and heuristic approaches. Deterministic methods include knowledge-based statistical methods, rotamer libraries, homology modeling, the build-up method, self-consistent electrostatic field, deformation methods, tree-based elimination and eigenvector following routines. The heuristic methods include Monte Carlo chain growing, energy minimizations, metropolis monte carlo and molecular dynamics. In addition, various methods to enhance the conformational search including the deformation or smoothing of the surface, scaling of system parameters, and multi copy searching are also discussed.

  12. Low Power Magnetic Bearing Design for High Speed Rotating Machinery

    NASA Technical Reports Server (NTRS)

    Allaire, P. E.; Maslen, E. H.; Humphris, R. R.; Sortore, C. K.; Studer, P. A.

    1992-01-01

    Magnetic suspension technology has advanced to the point of being able to offer a number of advantages to a variety of applications in the rotating machinery and aerospace fields. One strong advantage is the decrease in power consumption. The design and construction of a set of permanent magnet biased, actively controlled magnetic bearing for a flexible rotor are presented. Both permanent magnets and electromagnets are used in a configuration which effectively provides the necessary fluxes in the appropriate air gaps, while simultaneously keeping the undesirable destabilizing forces to a minimum. The design includes two radial bearings and a thrust bearing. The theoretical development behind the design is briefly discussed. Experimental performance results for a set of operating prototype bearings is presented. The results include measurements of load capacity, bearing stiffness and damping, and the dynamic response of the rotor. With few exceptions, the experimental results matched very well with the predicted performance. The power consumption of these bearings was found to be significantly reduced from that for a comparable set of all electromagnetic bearings.

  13. Arms Race between Enveloped Viruses and the Host ERAD Machinery

    PubMed Central

    Frabutt, Dylan A.; Zheng, Yong-Hui

    2016-01-01

    Enveloped viruses represent a significant category of pathogens that cause serious diseases in animals. These viruses express envelope glycoproteins that are singularly important during the infection of host cells by mediating fusion between the viral envelope and host cell membranes. Despite low homology at protein levels, three classes of viral fusion proteins have, as of yet, been identified based on structural similarities. Their incorporation into viral particles is dependent upon their proper sub-cellular localization after being expressed and folded properly in the endoplasmic reticulum (ER). However, viral protein expression can cause stress in the ER, and host cells respond to alleviate the ER stress in the form of the unfolded protein response (UPR); the effects of which have been observed to potentiate or inhibit viral infection. One important arm of UPR is to elevate the capacity of the ER-associated protein degradation (ERAD) pathway, which is comprised of host quality control machinery that ensures proper protein folding. In this review, we provide relevant details regarding viral envelope glycoproteins, UPR, ERAD, and their interactions in host cells. PMID:27657106

  14. Interactions of release factor RF3 with the translation machinery.

    PubMed

    O'Connor, Michael

    2015-08-01

    The bacterial release factor RF3 is a GTPase that has been implicated in multiple, incompletely understood steps of protein synthesis. This study explores the genetic interaction of RF3 with other components of the translation machinery. RF3 contributes to translation termination by recycling the class I release factors RF1 and RF2 off post-termination ribosomes. RF3 has also been implicated in dissociation of peptidyl-tRNAs from elongating ribosomes and in a post-peptidyltransferase quality control (post-PT QC) mechanism that selectively terminates ribosomes carrying erroneous peptides. A majority of the in vivo studies on RF3 have been carried out in K-12 strains of Escherichia coli which carry a partially defective RF2 protein with an Ala to Thr substitution at position 246. Here, the contribution of the K-12 specific RF2 variant to RF3 activities has been investigated. Strain reconstruction experiments in both E. coli and Salmonella enterica demonstrate that defects in termination and post-PT QC that are associated with RF3 loss, as well as phenotypes uncovered by phenotypic profiling, are all substantially ameliorated when the incompletely active K-12-specific RF2 protein is replaced by a fully active Ala246 RF2. These results indicate that RF3 loss is well tolerated in bacteria with fully active class I release factors, but that many of the previously reported phenotypes for RF3 deletion strains have been compromised by the presence of a partially defective RF2.

  15. Low power magnetic bearing design for high speed rotating machinery

    NASA Astrophysics Data System (ADS)

    Allaire, P. E.; Maslen, E. H.; Humphris, R. R.; Sortore, C. K.; Studer, P. A.

    1992-05-01

    Magnetic suspension technology has advanced to the point of being able to offer a number of advantages to a variety of applications in the rotating machinery and aerospace fields. One strong advantage is the decrease in power consumption. The design and construction of a set of permanent magnet biased, actively controlled magnetic bearing for a flexible rotor are presented. Both permanent magnets and electromagnets are used in a configuration which effectively provides the necessary fluxes in the appropriate air gaps, while simultaneously keeping the undesirable destabilizing forces to a minimum. The design includes two radial bearings and a thrust bearing. The theoretical development behind the design is briefly discussed. Experimental performance results for a set of operating prototype bearings is presented. The results include measurements of load capacity, bearing stiffness and damping, and the dynamic response of the rotor. With few exceptions, the experimental results matched very well with the predicted performance. The power consumption of these bearings was found to be significantly reduced from that for a comparable set of all electromagnetic bearings.

  16. 46 CFR 91.15-1 - Standards in inspection of hulls, boilers, and machinery.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 4 2014-10-01 2014-10-01 false Standards in inspection of hulls, boilers, and machinery... hulls, boilers, and machinery. In the inspection of hulls, boilers, and machinery of vessels, the..., respecting material and inspection of hulls, boilers, and machinery, and the certificate of...

  17. 46 CFR 189.15-1 - Standards in inspection of hulls, boilers, and machinery.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Standards in inspection of hulls, boilers, and machinery... inspection of hulls, boilers, and machinery. In the inspection of hulls, boilers, and machinery of vessels... chapter, respecting material and construction of hulls, boilers, and machinery, and certificate...

  18. 46 CFR 189.15-1 - Standards in inspection of hulls, boilers, and machinery.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Standards in inspection of hulls, boilers, and machinery... inspection of hulls, boilers, and machinery. In the inspection of hulls, boilers, and machinery of vessels... chapter, respecting material and construction of hulls, boilers, and machinery, and certificate...

  19. 46 CFR 71.15-1 - Standards in inspection of hulls, boilers, and machinery.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 3 2012-10-01 2012-10-01 false Standards in inspection of hulls, boilers, and machinery..., boilers, and machinery. In the inspection of hulls, boilers, and machinery of vessels, the standards... and inspection of hulls, boilers, and machinery, and the certificate of classification...

  20. 46 CFR 91.15-1 - Standards in inspection of hulls, boilers, and machinery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Standards in inspection of hulls, boilers, and machinery... hulls, boilers, and machinery. In the inspection of hulls, boilers, and machinery of vessels, the..., respecting material and inspection of hulls, boilers, and machinery, and the certificate of...