Science.gov

Sample records for 12-kilovolt kv overhead

  1. Final joint environmental assessment for the construction and routine operation of a 12-kilovolt (KV) overhead powerline right-of-way, and formal authorization for a 10-inch and 8-inch fresh water pipeline right-of-way, Naval Petroleum Reserve No. 1, Kern County, California

    SciTech Connect

    Not Available

    1994-10-01

    The purpose and need of the proposed action, which is the installation of an overhead powerline extension from an Naval Petroleum Reserve No. 1 (NPR-1) power source to the WKWD Station A, is to significantly reduce NPR-1`s overall utility costs. While the proposed action is independently justified on its own merits and is not tied to the proposed NPR-1 Cogeneration Facility, the proposed action would enable DOE to tie the NPR-1 fresh water pumps at Station A into the existing NPR-1 electrical distribution system. With the completion of the cogeneration facility in late 1994 or early 1995, the proposed action would save additional utility costs. This report deals with the environmental impacts of the construction of the powerline and the water pipeline. In addition, information is given about property rights and attaining permission to cross the property of proposed affected owners.

  2. Increasing the reliability of the shutdown of 500 - 750-kV overhead lines equipped with shunt reactors in an unsuccessful three-phase automatic repeated closure cycle

    SciTech Connect

    Kuz'micheva, K. I.; Merzlyakov, A. S.; Fokin, G. G.

    2013-05-15

    The reasons for circuit-breaker failures during repeated disconnection of 500 - 750 kV overhead lines with shunt reactors in a cycle of unsuccessful three-phase automatic reconnection (TARC) are analyzed. Recommendations are made for increasing the operating reliability of power transmission lines with shunt reactors when there is unsuccessful reconnection.

  3. a Distance Protection Strategic Spare Relay for 132/66 kv Overhead Lines

    NASA Astrophysics Data System (ADS)

    Harris, R. T.; Roberts, A. G.; Marks, A.; Phipps, W.

    2010-06-01

    The South African electrical supply utility (Eskom) has been experiencing problems in the field of protection, maintenance and in-service breakdowns which influence the quality of electrical supply to the consumer, an important and integral component of the utility business. As a result, further development of the generic relay, implemented as a strategic spare relay for the replacement of several schemes operating within Eskom's southern region has been initiated. These include the electromechanical, solid state and numerical distance protection relays and scheme failures on the 132/66 kV feeder network. The research considers the development, testing and configuration of the strategic spare relay in terms of software and peripheral hardware for the input and output terminal connections, generic equations and settings, for the purpose of scheme replacements. The various schemes are assessed for stepped distance and permissive intertripping for three and single pole operation. This is done in conjunction with the internal and external circuit diagrams to understand the detailed operation of the scheme and to ensure the effective implementation of the strategic spare relay. The generic relay is configured for the emergency replacement of the various schemes during in-service breakdowns. This constitutes a temporary installation and therefore the downtime of all the distance protection schemes that require replacement, is limited to a minimum.

  4. Power System Reliability Assessment by Analysing Voltage Dips on the Blue Horizon Bay 22KV Overhead Line in the Nelson Mandela Bay Municipality

    NASA Astrophysics Data System (ADS)

    Lamour, B. G.; Harris, R. T.; Roberts, A. G.

    2010-06-01

    Power system reliability problems are very difficult to solve because the power systems are complex and geographically widely distributed and influenced by numerous unexpected events. It is therefore imperative to employ the most efficient optimization methods in solving the problems relating to reliability of the power system. This paper presents a reliability analysis and study of the power interruptions resulting from severe power outages in the Nelson Mandela Bay Municipality (NMBM), South Africa and includes an overview of the important factors influencing reliability, and methods to improve the reliability. The Blue Horizon Bay 22 kV overhead line, supplying a 6.6 kV residential sector has been selected. It has been established that 70% of the outages, recorded at the source, originate on this feeder.

  5. Overhead Projector Demonstrations.

    ERIC Educational Resources Information Center

    Hambly, Gordon F.; Goldsmith, Robert H.

    1988-01-01

    Presented is a method of demonstrating the optical activity of glucose using an overhead projector and easily obtainable materials. Explores the difference between reflected and transmitted light (Tyndall Effect) using sodium thiosulfate, hydrochloric acid, and an overhead projector. (ML)

  6. Overhead Image Statistics

    SciTech Connect

    Vijayaraj, Veeraraghavan; Cheriyadat, Anil M; Bhaduri, Budhendra L; Vatsavai, Raju; Bright, Eddie A

    2008-01-01

    Statistical properties of high-resolution overhead images representing different land use categories are analyzed using various local and global statistical image properties based on the shape of the power spectrum, image gradient distributions, edge co-occurrence, and inter-scale wavelet coefficient distributions. The analysis was performed on a database of high-resolution (1 meter) overhead images representing a multitude of different downtown, suburban, commercial, agricultural and wooded exemplars. Various statistical properties relating to these image categories and their relationship are discussed. The categorical variations in power spectrum contour shapes, the unique gradient distribution characteristics of wooded categories, the similarity in edge co-occurrence statistics for overhead and natural images, and the unique edge co-occurrence statistics of downtown categories are presented in this work. Though previous work on natural image statistics has showed some of the unique characteristics for different categories, the relationships for overhead images are not well understood. The statistical properties of natural images were used in previous studies to develop prior image models, to predict and index objects in a scene and to improve computer vision models. The results from our research findings can be used to augment and adapt computer vision algorithms that rely on prior image statistics to process overhead images, calibrate the performance of overhead image analysis algorithms, and derive features for better discrimination of overhead image categories.

  7. Overhead Projector Demonstrations.

    ERIC Educational Resources Information Center

    Kolb, Doris, Ed.

    1989-01-01

    Described are demonstrations of the optical activity of two sugar solutions, and the effects of various substituents on acid strength using an overhead projector. Materials and procedures for each demonstration are discussed. (CW)

  8. Anania Shirakatsi's Overheads System

    NASA Astrophysics Data System (ADS)

    Eynatyan, Julieta

    2014-10-01

    A review of Anania Shirakatsi's overheads system is given based on his chronological works. Lunar, solar and lunisolar calendars are discussed. Anania Shirakatsi is presented as having an important role in the establishment of the Armenian unique chronology.

  9. Overhead Projector Demonstrations.

    ERIC Educational Resources Information Center

    Kolb, Doris, Ed.

    1988-01-01

    Details two demonstrations for use with an overhead projector in a chemistry lecture. Includes "A Very Rapidly Growing Silicate Crystal" and "A Colorful Demonstration to Simulate Orbital Hybridization." The materials and directions for each demonstration are included as well as a brief explanation of the essential learning involved. (CW)

  10. Kv5, Kv6, Kv8, and Kv9 subunits: No simple silent bystanders

    PubMed Central

    2016-01-01

    Members of the electrically silent voltage-gated K+ (Kv) subfamilies (Kv5, Kv6, Kv8, and Kv9, collectively identified as electrically silent voltage-gated K+ channel [KvS] subunits) do not form functional homotetrameric channels but assemble with Kv2 subunits into heterotetrameric Kv2/KvS channels with unique biophysical properties. Unlike the ubiquitously expressed Kv2 subunits, KvS subunits show a more restricted expression. This raises the possibility that Kv2/KvS heterotetramers have tissue-specific functions, making them potential targets for the development of novel therapeutic strategies. Here, I provide an overview of the expression of KvS subunits in different tissues and discuss their proposed role in various physiological and pathophysiological processes. This overview demonstrates the importance of KvS subunits and Kv2/KvS heterotetramers in vivo and the importance of considering KvS subunits and Kv2/KvS heterotetramers in the development of novel treatments. PMID:26755771

  11. Overhead camshaft engine

    SciTech Connect

    Honma, M.

    1987-07-21

    This patent describes an overhead camshaft engine comprising: a cylinder block; a cylinder head; a fastening member for fastening the cylinder head to the cylinder block; a valve reciprocally mounted in the cylinder head; and a camshaft rotatably mounted over the cylinder head to control reciprocation of the valve; the camshaft being so arranged, with respect to a plan view, as to lap in part over the fastening member and formed with a peripheral cut at a portion where it laps over the fastening member to facilitate insertion and removal of the fastening member.

  12. Overhead-valve engine

    SciTech Connect

    Tamba, S.; Miyake, H.; Fukui, N.

    1987-05-05

    An overhead valve engine is described comprising: push rod receiving bores, at least one of the push rod receiving bores being maintained in communication at one end with a crank chamber and at an opposite end with a rocker arm chamber and at least one other push rod receiving bore being maintained in communication with the rocker arm chamber; push rods contained within push rod receiving bores; and a breather chamber in communication with at least one other push rod receiving bore in the vicinity of a camshaft.

  13. Manipulator system for constructing overhead distribution lines

    SciTech Connect

    Ohnishi, H.; Tsuchihashi, H.; Waki, S.; Mochizuki, K. ); Yamamoto, T.; Watanabe, H. ); Furukawa, H. )

    1993-04-01

    This paper describes the manipulator for live-line construction of high-voltage overhead power transmission lines (line voltage 6.6 kV) that is being jointly developed by Tokyo Electric Power and other companies. It describes this system's development concept, makeup, functions, and design, as well as operability tests using actual-scale transmission line poles. In this research, development began in 1984. As the first step, a prototype model of a ground-mounted twin-arm manipulator was trial-manufactured in 1985. As the second step, in 1988 a truck-mounted system was developed in which the twin-arm manipulator was mounted on a cherrypicker vehicle. As the third step, a practical system was developed based on these results.

  14. Electrical and mechanical design criteria for EHV and UHV: overhead transmission lines

    SciTech Connect

    Not Available

    1980-06-01

    The results are presented of a program devoted to the selection of electrical and mechanical design criteria and parameters for overhead power transmission lines for ac systems rated at from 345 to 1100 kV and for dc systems rated at from 600 to 1200 kV. Information is included on the environmental effects, i.e., audible noise and electric fields, of the lines, mechanical and economic requirements, safety, failures, grounding, and lightning protection. (LCL)

  15. Spectroscopy on the Overhead Projector.

    ERIC Educational Resources Information Center

    Solomon, Sally; And Others

    1994-01-01

    Any overhead projector easily can be converted into a simple spectrometer by placing a piece of diffraction grating over the projecting lens. A detailed description of the apparatus and suggested spectroscopy experiments are included. Demonstrations can utilize solutions of cobalt chloride, potassium permanganate, potassium dichromate, or…

  16. Creating Great Overheads with Computers.

    ERIC Educational Resources Information Center

    Gribas, Cyndy; And Others

    1996-01-01

    Steps in preparing effective overhead projector transparencies for college instruction are outlined, using the PowerPoint program for Windows. They include thinking analogically in translating from concept to visual form; using the features of the presentation program to create a polished product; and assuring readability (visibility, typeface…

  17. First structure on MoronytoRainbow 100kV Transmission Line below Morony Dam ...

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

    First structure on Morony-to-Rainbow 100kV Transmission Line below Morony Dam and Power House. Three-pole H-frame structure with historic porcelain suspension insulators, jumper supports insulators, overhead ground wires, and pole stubs. View to east-northeast - Morony Hydroelectric Facility, Morony-to-Rainbow 100 kV Transmission Line, West bank of the Missouri River, Great Falls, Cascade County, MT

  18. Quantum compiling with low overhead

    NASA Astrophysics Data System (ADS)

    Duclos-Cianci, Guillaume; Poulin, David

    2014-03-01

    I will present a scheme to compile complex quantum gates that uses significantly fewer resources than existing schemes. In standard fault-tolerant protocols, a magic state is distilled from noisy resources, and copies of this magic state are then assembled into produced complex gates using the Solovay-Kitaev theorem or variants thereof. In our approach, we instead directly distill magic states associated to complex gates from noisy resources, leading to a reduction of the compiling overhead of several orders of magnitude.

  19. Proximal Biceps in Overhead Athletes.

    PubMed

    Chalmers, Peter N; Verma, Nikhil N

    2016-01-01

    The proximal long head of the biceps tendon and its attachment at the superior glenoid tubercle and labrum are subject to a spectrum of disorders in overhead athletes. Biceps disorders are commonly characterized by intermittent anterior or deep-seated shoulder pain exacerbated by activity. Diagnosis is reached via various physical examination maneuvers; MRI can be uncertain. Nonsteroidal anti-inflammatory medications, targeted ultrasound-guided corticosteroid injections, and supervised physical therapy are the mainstays of nonoperative treatment. Operative treatment, which remains controversial, provides reliable pain relief, restoration of function for activities of daily living, and low complication rates, but return to play can be unpredictable.

  20. Overhead Door Company of Charleston Information Sheet

    EPA Pesticide Factsheets

    Overhead Door Company of Charleston (the Company) is located in North Charleston, South Carolina. The settlement involves renovation activities conducted at a property constructed prior to 1978, located in Isle of Palms, South Carolina.

  1. 29 CFR 1926.1438 - Overhead & gantry cranes.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 8 2012-07-01 2012-07-01 false Overhead & gantry cranes. 1926.1438 Section 1926.1438 Labor... Overhead & gantry cranes. (a) Permanently installed overhead and gantry cranes. The requirements of § 1910... equipment when used in construction and permanently installed in a facility: overhead and gantry...

  2. 29 CFR 1926.1438 - Overhead & gantry cranes.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 8 2014-07-01 2014-07-01 false Overhead & gantry cranes. 1926.1438 Section 1926.1438 Labor... Overhead & gantry cranes. (a) Permanently installed overhead and gantry cranes. The requirements of § 1910... equipment when used in construction and permanently installed in a facility: overhead and gantry...

  3. 29 CFR 1926.1438 - Overhead & gantry cranes.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 8 2011-07-01 2011-07-01 false Overhead & gantry cranes. 1926.1438 Section 1926.1438 Labor... Overhead & gantry cranes. (a) Permanently installed overhead and gantry cranes. The requirements of § 1910... equipment when used in construction and permanently installed in a facility: overhead and gantry...

  4. 29 CFR 1926.1438 - Overhead & gantry cranes.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 8 2013-07-01 2013-07-01 false Overhead & gantry cranes. 1926.1438 Section 1926.1438 Labor... Overhead & gantry cranes. (a) Permanently installed overhead and gantry cranes. The requirements of § 1910... equipment when used in construction and permanently installed in a facility: overhead and gantry...

  5. Overhead-Aware-Best-Fit (OABF) Resource Allocation Algorithm for Minimizing VM Launching Overhead

    SciTech Connect

    Wu, Hao; Garzoglio, Gabriele; Ren, Shangping; Timm, Steven; Noh, Seo Young

    2014-11-11

    FermiCloud is a private cloud developed in Fermi National Accelerator Laboratory to provide elastic and on-demand resources for different scientific research experiments. The design goal of the FermiCloud is to automatically allocate resources for different scientific applications so that the QoS required by these applications is met and the operational cost of the FermiCloud is minimized. Our earlier research shows that VM launching overhead has large variations. If such variations are not taken into consideration when making resource allocation decisions, it may lead to poor performance and resource waste. In this paper, we show how we may use an VM launching overhead reference model to minimize VM launching overhead. In particular, we first present a training algorithm that automatically tunes a given refer- ence model to accurately reflect FermiCloud environment. Based on the tuned reference model for virtual machine launching overhead, we develop an overhead-aware-best-fit resource allocation algorithm that decides where and when to allocate resources so that the average virtual machine launching overhead is minimized. The experimental results indicate that the developed overhead-aware-best-fit resource allocation algorithm can significantly improved the VM launching time when large number of VMs are simultaneously launched.

  6. Mechanosensitive gating of Kv channels.

    PubMed

    Morris, Catherine E; Prikryl, Emil A; Joós, Béla

    2015-01-01

    K-selective voltage-gated channels (Kv) are multi-conformation bilayer-embedded proteins whose mechanosensitive (MS) Popen(V) implies that at least one conformational transition requires the restructuring of the channel-bilayer interface. Unlike Morris and colleagues, who attributed MS-Kv responses to a cooperative V-dependent closed-closed expansion↔compaction transition near the open state, Mackinnon and colleagues invoke expansion during a V-independent closed↔open transition. With increasing membrane tension, they suggest, the closed↔open equilibrium constant, L, can increase >100-fold, thereby taking steady-state Popen from 0→1; "exquisite sensitivity to small…mechanical perturbations", they state, makes a Kv "as much a mechanosensitive…as…a voltage-dependent channel". Devised to explain successive gK(V) curves in excised patches where tension spontaneously increased until lysis, their L-based model falters in part because of an overlooked IK feature; with recovery from slow inactivation factored in, their g(V) datasets are fully explained by the earlier model (a MS V-dependent closed-closed transition, invariant L≥4). An L-based MS-Kv predicts neither known Kv time courses nor the distinctive MS responses of Kv-ILT. It predicts Kv densities (hence gating charge per V-sensor) several-fold different from established values. If opening depended on elevated tension (L-based model), standard gK(V) operation would be compromised by animal cells' membrane flaccidity. A MS V-dependent transition is, by contrast, unproblematic on all counts. Since these issues bear directly on recent findings that mechanically-modulated Kv channels subtly tune pain-related excitability in peripheral mechanoreceptor neurons we undertook excitability modeling (evoked action potentials). Kvs with MS V-dependent closed-closed transitions produce nuanced mechanically-modulated excitability whereas an L-based MS-Kv yields extreme, possibly excessive (physiologically

  7. Viewing Vertical Objects with an Overhead Projector.

    ERIC Educational Resources Information Center

    Wild, R. L.

    1988-01-01

    Discusses the use of an overhead projector for the deflection of a vertical image to a screen. Describes three demonstrations: magnetizing of a steel ball bearing and paper clip; convection currents of a hot liquid within a cold liquid; and oscillation of concentrated salt solution into fresh water. (YP)

  8. 30 CFR 56.12045 - Overhead powerlines.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Overhead powerlines. 56.12045 Section 56.12045 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Electricity §...

  9. 30 CFR 56.12045 - Overhead powerlines.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Overhead powerlines. 56.12045 Section 56.12045 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Electricity §...

  10. 30 CFR 56.12045 - Overhead powerlines.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Overhead powerlines. 56.12045 Section 56.12045 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Electricity §...

  11. 30 CFR 56.12045 - Overhead powerlines.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Overhead powerlines. 56.12045 Section 56.12045 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Electricity §...

  12. 30 CFR 56.12045 - Overhead powerlines.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Overhead powerlines. 56.12045 Section 56.12045 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Electricity §...

  13. The Overhead Projector in the Mathematics Classroom.

    ERIC Educational Resources Information Center

    Lenchner, George

    The first section of this pamphlet illustrates and describes the overhead projector, and discusses several of its advantages over other projection devises, including its simplicity of operation, conservation of class time, dynamic effects, image size, etc. The second section describes in some detail materials and methods used to make visuals, then…

  14. Centripetal Force on an Overhead Projector.

    ERIC Educational Resources Information Center

    Rheam, Harry

    1995-01-01

    Describes two simple demonstrations of an object moving in a straight line tangent to the circle if centripetal force is removed. Demonstrations use a pie plate and petri dish with ball bearings to illustrate the phenomena on an overhead projector. (LZ)

  15. Overhead Projection Cell for Streamline Flow

    ERIC Educational Resources Information Center

    Waage, Harold M.

    1969-01-01

    Describes the construction and operation of an overhead projection apparatus designed to demonstrate streamline flow of a liquid. The apparatus consists of a Plexiglass tank containing water in which plates forming the cell are submerged, a constant level reservoir, an overflow device and a system for marking the flow lines with a dye. (LC)

  16. 23 CFR 140.907 - Overhead and indirect construction costs.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... which assure proper control and distribution of the overhead and indirect construction costs. ... 23 Highways 1 2012-04-01 2012-04-01 false Overhead and indirect construction costs. 140.907... REIMBURSEMENT Reimbursement for Railroad Work § 140.907 Overhead and indirect construction costs. (a) A...

  17. 30 CFR 56.14108 - Overhead drive belts.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Overhead drive belts. 56.14108 Section 56.14108 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... Safety Devices and Maintenance Requirements § 56.14108 Overhead drive belts. Overhead drive belts...

  18. 30 CFR 57.14108 - Overhead drive belts.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Overhead drive belts. 57.14108 Section 57.14108 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... Equipment Safety Devices and Maintenance Requirements § 57.14108 Overhead drive belts. Overhead drive...

  19. 30 CFR 56.14108 - Overhead drive belts.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Overhead drive belts. 56.14108 Section 56.14108 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... Safety Devices and Maintenance Requirements § 56.14108 Overhead drive belts. Overhead drive belts...

  20. 30 CFR 56.14108 - Overhead drive belts.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Overhead drive belts. 56.14108 Section 56.14108 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... Safety Devices and Maintenance Requirements § 56.14108 Overhead drive belts. Overhead drive belts...

  1. 30 CFR 57.14108 - Overhead drive belts.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Overhead drive belts. 57.14108 Section 57.14108 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... Equipment Safety Devices and Maintenance Requirements § 57.14108 Overhead drive belts. Overhead drive...

  2. 30 CFR 56.14108 - Overhead drive belts.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Overhead drive belts. 56.14108 Section 56.14108 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... Safety Devices and Maintenance Requirements § 56.14108 Overhead drive belts. Overhead drive belts...

  3. 30 CFR 57.14108 - Overhead drive belts.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Overhead drive belts. 57.14108 Section 57.14108 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... Equipment Safety Devices and Maintenance Requirements § 57.14108 Overhead drive belts. Overhead drive...

  4. 30 CFR 57.14108 - Overhead drive belts.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Overhead drive belts. 57.14108 Section 57.14108 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... Equipment Safety Devices and Maintenance Requirements § 57.14108 Overhead drive belts. Overhead drive...

  5. 30 CFR 57.14108 - Overhead drive belts.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Overhead drive belts. 57.14108 Section 57.14108 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... Equipment Safety Devices and Maintenance Requirements § 57.14108 Overhead drive belts. Overhead drive...

  6. 30 CFR 56.14108 - Overhead drive belts.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Overhead drive belts. 56.14108 Section 56.14108 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... Safety Devices and Maintenance Requirements § 56.14108 Overhead drive belts. Overhead drive belts...

  7. Human Factors Engineering Guidelines for Overhead Cranes

    NASA Technical Reports Server (NTRS)

    Chandler, Faith; Delgado, H. (Technical Monitor)

    2001-01-01

    This guideline provides standards for overhead crane cabs that can be applied to the design and modification of crane cabs to reduce the potential for human error due to design. This guideline serves as an aid during the development of a specification for purchases of cranes or for an engineering support request for crane design modification. It aids human factors engineers in evaluating existing cranes during accident investigations or safety reviews.

  8. Shoulder Injuries in the Overhead Throwing Athlete.

    PubMed

    Mlynarek, Ryan A; Lee, Simon; Bedi, Asheesh

    2017-02-01

    The overhead pitching motion is a coordinated sequence of movements that subjects the shoulder to extreme forces. The ultimate goal of this complex, dynamic activity is to generate high ball velocity and accuracy. In doing so, repetitive throwing can cause adaptive and pathologic changes in the thrower's shoulder. This article reviews the relevant shoulder anatomy, the kinetic chain, and throwing mechanics, as well as common shoulder injuries and surgical options for the treating orthopedic surgeon.

  9. Kv7 and Kv11 channels in myometrial regulation

    PubMed Central

    Greenwood, Iain A; Tribe, Rachel M

    2014-01-01

    Ion channels play a key role in defining myometrial contractility. Modulation of ion channel populations is proposed to underpin gestational changes in uterine contractility associated with the transition from uterine quiescence to active labour. Of the myriad ion channels present in the uterus, this article will focus upon potassium channels encoded by the KCNQ genes and ether-à-go-go-related (ERG) genes. Voltage-gated potassium channels encoded by KCNQ and ERG (termed Kv7 and Kv11, respectively) are accepted as major determinants of neuronal excitability and the duration of the cardiac action potential. However, there is now growing appreciation that these ion channels have a major functional impact in vascular and non-vascular smooth muscle. Moreover, Kv7 channels may be potential therapeutic targets for the treatment of preterm labour. PMID:24121285

  10. Predictive model of avian electrocution risk on overhead power lines.

    PubMed

    Dwyer, J F; Harness, R E; Donohue, K

    2014-02-01

    Electrocution on overhead power structures negatively affects avian populations in diverse ecosystems worldwide, contributes to the endangerment of raptor populations in Europe and Africa, and is a major driver of legal action against electric utilities in North America. We investigated factors associated with avian electrocutions so poles that are likely to electrocute a bird can be identified and retrofitted prior to causing avian mortality. We used historical data from southern California to identify patterns of avian electrocution by voltage, month, and year to identify species most often killed by electrocution in our study area and to develop a predictive model that compared poles where an avian electrocution was known to have occurred (electrocution poles) with poles where no known electrocution occurred (comparison poles). We chose variables that could be quantified by personnel with little training in ornithology or electric systems. Electrocutions were more common at distribution voltages (≤ 33 kV) and during breeding seasons and were more commonly reported after a retrofitting program began. Red-tailed Hawks (Buteo jamaicensis) (n = 265) and American Crows (Corvus brachyrhynchos) (n = 258) were the most commonly electrocuted species. In the predictive model, 4 of 14 candidate variables were required to distinguish electrocution poles from comparison poles: number of jumpers (short wires connecting energized equipment), number of primary conductors, presence of grounding, and presence of unforested unpaved areas as the dominant nearby land cover. When tested against a sample of poles not used to build the model, our model distributed poles relatively normally across electrocution-risk values and identified the average risk as higher for electrocution poles relative to comparison poles. Our model can be used to reduce avian electrocutions through proactive identification and targeting of high-risk poles for retrofitting.

  11. Mechanosensitive Gating of Kv Channels

    PubMed Central

    Morris, Catherine E.; Prikryl, Emil A.; Joós, Béla

    2015-01-01

    K-selective voltage-gated channels (Kv) are multi-conformation bilayer-embedded proteins whose mechanosensitive (MS) Popen(V) implies that at least one conformational transition requires the restructuring of the channel-bilayer interface. Unlike Morris and colleagues, who attributed MS-Kv responses to a cooperative V-dependent closed-closed expansion↔compaction transition near the open state, Mackinnon and colleagues invoke expansion during a V-independent closed↔open transition. With increasing membrane tension, they suggest, the closed↔open equilibrium constant, L, can increase >100-fold, thereby taking steady-state Popen from 0→1; “exquisite sensitivity to small…mechanical perturbations”, they state, makes a Kv “as much a mechanosensitive…as…a voltage-dependent channel”. Devised to explain successive gK(V) curves in excised patches where tension spontaneously increased until lysis, their L-based model falters in part because of an overlooked IK feature; with recovery from slow inactivation factored in, their g(V) datasets are fully explained by the earlier model (a MS V-dependent closed-closed transition, invariant L≥4). An L-based MS-Kv predicts neither known Kv time courses nor the distinctive MS responses of Kv-ILT. It predicts Kv densities (hence gating charge per V-sensor) several-fold different from established values. If opening depended on elevated tension (L-based model), standard gK(V) operation would be compromised by animal cells’ membrane flaccidity. A MS V-dependent transition is, by contrast, unproblematic on all counts. Since these issues bear directly on recent findings that mechanically-modulated Kv channels subtly tune pain-related excitability in peripheral mechanoreceptor neurons we undertook excitability modeling (evoked action potentials). Kvs with MS V-dependent closed-closed transitions produce nuanced mechanically-modulated excitability whereas an L-based MS-Kv yields extreme, possibly excessive

  12. Claims for Unabsorbed Overhead on Defense Contracts.

    DTIC Science & Technology

    1985-09-01

    increase overhead costs" (7:20). In a concurring opinion, Administrative Judge Lieblich makes a couple of points very clear: (1) as far as this Board is...method of calculating these coats C7:13. Judge Lieblich than goes on to qualify his seemingly strong words about the "Eichleay" formula. He states...BCA, 83-2: 1-32 and (1-2 of Concurring opinio-f Judge Lieblich ) (17 February 1983). 8. Capital Electric co. vs. The United States, No. 83-965, CAFC: 1

  13. Kv1.3/Kv1.5 heteromeric channels compromise pharmacological responses in macrophages

    SciTech Connect

    Villalonga, Nuria; Escalada, Artur; Vicente, Ruben; Sanchez-Tillo, Ester; Celada, Antonio; Solsona, Carles; Felipe, Antonio . E-mail: afelipe@ub.edu

    2007-01-26

    Voltage-dependent K{sup +} (Kv) channels are involved in the immune response. Kv1.3 is highly expressed in activated macrophages and T-effector memory cells of autoimmune disease patients. Macrophages are actively involved in T-cell activation by cytokine production and antigen presentation. However, unlike T-cells, macrophages express Kv1.5, which is resistant to Kv1.3-drugs. We demonstrate that mononuclear phagocytes express different Kv1.3/Kv1.5 ratios, leading to biophysically and pharmacologically distinct channels. Therefore, Kv1.3-based treatments to alter physiological responses, such as proliferation and activation, are impaired by Kv1.5 expression. The presence of Kv1.5 in the macrophagic lineage should be taken into account when designing Kv1.3-based therapies.

  14. Troubleshooting crude vacuum tower overhead ejector systems

    SciTech Connect

    Lines, J.R.; Frens, L.L. )

    1995-03-01

    Routinely surveying tower overhead vacuum systems can improve performance and product quality. These vacuum systems normally provide reliable and consistent operation. However, process conditions, supplied utilities, corrosion, erosion and fouling all have an impact on ejector system performance. Refinery vacuum distillation towers use ejector systems to maintain tower top pressure and remove overhead gases. However, as with virtually all refinery equipment, performance may be affected by a number of variables. These variables may act independently or concurrently. It is important to understand basic operating principles of vacuum systems and how performance is affected by: utilities, corrosion and erosion, fouling, and process conditions. Reputable vacuum-system suppliers have service engineers that will come to a refinery to survey the system and troubleshoot performance or offer suggestions for improvement. A skilled vacuum-system engineer may be needed to diagnose and remedy system problems. The affect of these variables on performance is discussed. A case history is described of a vacuum system on a crude tower in a South American refinery.

  15. Mechanics and pathomechanics in the overhead athlete.

    PubMed

    Kibler, W Ben; Wilkes, Trevor; Sciascia, Aaron

    2013-10-01

    Optimal performance of the overhead throwing task requires precise mechanics that involve coordinated kinetic and kinematic chains to develop, transfer, and regulate the forces the body needs to withstand the inherent demands of the task and to allow optimal performance. These chains have been evaluated and the basic components, called nodes, have been identified. Impaired performance and/or injury, the DTS, is associated with alterations in the mechanics that are called pathomechanics. They can occur at multiple locations throughout the kinetic chain. They must be evaluated and treated as part of the overall problem. Observational analysis of the mechanics and pathomechanics using the node analysis method can be useful in highlighting areas of alteration that can be evaluated for anatomic injury or altered physiology. The comprehensive kinetic chain examination can evaluate sites of kinetic chain breakage, and a detailed shoulder examination can assess joint internal derangement of altered physiology that may contribute to the pathomechanics. Treatment of the DTS should be comprehensive, directed toward restoring physiology and mechanics and optimizing anatomy. This maximizes the body’s ability to develop normal mechanics to accomplish the overhead throwing task.

  16. Overhead analysis of universal concatenated quantum codes

    NASA Astrophysics Data System (ADS)

    Chamberland, Christopher; Jochym-O'Connor, Tomas; Laflamme, Raymond

    2017-02-01

    We analyze the resource overhead of recently proposed methods for universal fault-tolerant quantum computation using concatenated codes. Namely, we examine the concatenation of the 7-qubit Steane code with the 15-qubit Reed-Muller code, which allows for the construction of the 49- and 105-qubit codes that do not require the need for magic state distillation for universality. We compute a lower bound for the adversarial noise threshold of the 105-qubit code and find it to be 8.33 ×10-6. We obtain a depolarizing noise threshold for the 49-qubit code of 9.69 ×10-4 which is competitive with the 105-qubit threshold result of 1.28 ×10-3 . We then provide lower bounds on the resource requirements of the 49- and 105-qubit codes and compare them with the surface code implementation of a logical T gate using magic state distillation. For the sampled input error rates and noise model, we find that the surface code achieves a smaller overhead compared to our concatenated schemes.

  17. Shoulder Pain in the Overhead Throwing Athlete

    PubMed Central

    Seroyer, Shane T.; Nho, Shane J.; Bach, Bernard R.; Bush-Joseph, Charles A.; Nicholson, Gregory P.; Romeo, Anthony A.

    2009-01-01

    Treatment of the overhead throwing athlete is among the more challenging aspects of orthopaedic sports medicine. Awareness and understanding of the throwing motion and the supraphysiologic forces to which the structures of the shoulder are subjected are essential to diagnosis and treatment. Pain and dysfunction in the throwing shoulder may be attributed to numerous etiologies, including scapular dysfunction, intrinsic glenohumeral pathology (capsulolabral structures), extrinsic musculature (rotator cuff), or neurovascular structures. Attention to throwing mechanics and appropriate stretching, strength, and conditioning programs may reduce the risk of injury in this highly demanding activity. Early discovery of symptoms, followed by conservative management with rest and rehabilitation with special attention to retraining mechanics may mitigate the need for surgical intervention. Prevention of injury is always more beneficial to the long-term health of the thrower than is surgical repair. An anatomic approach is used in this report, focusing on common etiologies of pain in the overhead thrower and emphasizing the clinical presentation and treatment. PMID:23015861

  18. 23. OVERALL OVERHEAD VIEW OF MARISCAL WORKS LOOKING NORTH, NORTHEAST. ...

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

    23. OVERALL OVERHEAD VIEW OF MARISCAL WORKS LOOKING NORTH, NORTHEAST. NOTICE REDWOOD TANK PLATFORM LOWER RIGHT FOREGROUND. - Mariscal Quicksilver Mine & Reduction Works, Terlingua, Brewster County, TX

  19. Physical examination of the overhead athlete's shoulder.

    PubMed

    Sewick, Amy; Kelly, John D; Rubin, Ben

    2012-03-01

    Overhead athletes seek the services of an orthopedic surgeon because of pain and/or dysfunction. It is important to address the cause of the symptoms more so than the source of the patient's pain, so that treatment will eliminate the problem rather than merely ameliorate symptoms temporarily. In order to accomplish a thorough assessment of shoulder function, the examiner must expand his/her view from isolated assessment of the glenohumeral joint range of motion, stability, assessment of rotator cuff strength, palpation and provocative maneuvers, and add assessment of the shoulder in the context of the kinetic chain. The examination of the thrower's shoulder, coupled with a thorough history, will usually provide a solid functional diagnosis and provide a good idea as to the presence of structural damage. As a result, the value of rehabilitation and the benefit of surgical intervention are made more predictable.

  20. Low-overhead accrual failure detector.

    PubMed

    Ren, Xiao; Dong, Jian; Liu, Hongwei; Li, Yang; Yang, Xiaozong

    2012-01-01

    Failure detectors are one of the fundamental components for building a distributed system with high availability. In order to maintain the efficiency and scalability of failure detection in a complicated large-scale distributed system, accrual failure detectors that can adapt to multiple applications have been studied extensively. In this paper, an new accrual failure detector--LA-FD with low system overhead has been proposed specifically for current mobile network equipment on the Internet whose processing power, memory space and power supply are all constrained. It does not rely on the probability distribution of message transmission time, or on the maintenance of a history message window. By simple calculation, LA-FD provides adaptive failure detection service with high accuracy to multiple upper applications. The related experiments and results have also been presented.

  1. Sidney-North Yuma 230-kV Transmission Line Project, Colorado and Nebraska

    SciTech Connect

    Not Available

    1991-06-01

    This report describes the need for a 230-kV overhead transmission line to supply power from Sidney, Nebraska to eastern Colorado. The alternative scenario compared to construction of the line is No Action. Rejected alternatives include underground lines and different routing paths, with a possible extension to the Sterling area. Both scenarios are evaluated for environmental effects, cost, and consequences for the eastern Colorado region. The proposed route is determined to be the environmentally preferred choice. 120 refs., 6 figs., 13 tabs. (MHB)

  2. 1. EAST SIDE OF OVERHEAD BOMB TRANSPORT RACK, WITH BUILDING ...

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

    1. EAST SIDE OF OVERHEAD BOMB TRANSPORT RACK, WITH BUILDING 343 AT LEFT AND BUILDING 328 AT RIGHT. VIEW TO WEST. - Rocky Mountain Arsenal, Overhead Bomb Transport Rack, 1580 feet South of December Seventh Avenue; 860 feet West of D Street, Commerce City, Adams County, CO

  3. Overhead View of Pathfinder Landing Site

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Planimetric (overhead view) map of the landing site, to a distance of 20 meters from the spacecraft. North is at the top in this and Plates 3-5. To produce this map, images were geometrically projected onto an assumed mean surface representing the ground. Features above the ground plane (primarily rocks) therefore appear displaced radially outward; the amount of distortion increases systematically with distance. The upper surfaces of the lander and rover also appear enlarged and displaced because of their height. Primary grid (white) is based on the Landing Site Cartographic (LSC) coordinate system, defined with X eastward, Y north, and Z up, and origin located at the mean ground surface immediately beneath the deployed position of the IMP camera gimbal center. Secondary ticks (cyan) are based on the Mars local level (LL) frame, which has X north, Y east, Z down, with origin in the center of the lander baseplate. Rover positions (including APXS measurements) are commonly reported in the LL frame. Yellow grid shows polar coordinates based on the LSC system. Cartographic image processing by U.S. Geological Survey.

    NOTE: original caption as published in Science Magazine

    Mars Pathfinder is the second in NASA's Discovery program of low-cost spacecraft with highly focused science goals. The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C. JPL is a division of the California Institute of Technology (Caltech).

  4. Overhead View of Area Surrounding Pathfinder

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Overhead view of the area surrounding the Pathfinder lander illustrating the Sojourner traverse. Red rectangles are rover positions at the end of sols 1-30. Locations of soil mechanics experiments, wheel abrasion experiments, and APXS measurements are shown. The A numbers refer to APXS measurements as discussed in the paper by Rieder et al. (p. 1770, Science Magazine, see image note). Coordinates are given in the LL frame.

    The photorealistic, interactive, three-dimensional virtual reality (VR) terrain models were created from IMP images using a software package developed for Pathfinder by C. Stoker et al. as a participating science project. By matching features in the left and right camera, an automated machine vision algorithm produced dense range maps of the nearfield, which were projected into a three-dimensional model as a connected polygonal mesh. Distance and angle measurements can be made on features viewed in the model using a mouse-driven three-dimensional cursor and a point-and-click interface. The VR model also incorporates graphical representations of the lander and rover and the sequence and spatial locations at which rover data were taken. As the rover moved, graphical models of the rover were added for each position that could be uniquely determined using stereo images of the rover taken by the IMP. Images taken by the rover were projected into the model as two-dimensional 'billboards' to show the proper perspective of these images.

    NOTE: original caption as published in Science Magazine

    Mars Pathfinder is the second in NASA's Discovery program of low-cost spacecraft with highly focused science goals. The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C. JPL is a division of the California Institute of Technology (Caltech).

  5. Looking north toward unit 1 pump motor, overhead crane, and ...

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

    Looking north toward unit 1 pump motor, overhead crane, and double folding doors on the north side of the building - Wellton-Mohawk Irrigation System, Pumping Plant No. 2, Bounded by Interstate 8 to south, Wellton, Yuma County, AZ

  6. 2. TYPICAL OVERHEAD WIRE CONSTRUCTION CURVE GUY WIRE ARRANGEMENT ...

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

    2. TYPICAL OVERHEAD WIRE CONSTRUCTION - CURVE GUY WIRE ARRANGEMENT (ABANDONED WEST LEG OF WYE AT SIXTH AVENUE AND PINE STREET) - Yakima Valley Transportation Company Interurban Railroad, Trackage, Yakima, Yakima County, WA

  7. Interior view of main section of milk barn. Opening overhead ...

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

    Interior view of main section of milk barn. Opening overhead leads to attic crawl space. Camera is pointed SW. - Kosai Farm, Milk Barn, B Street north of Northwest Twenty-ninth Street, Auburn, King County, WA

  8. INTERIOR VIEW, SETTING LARGE CORE WITH ASSISTANCE FROM THE OVERHEAD ...

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

    INTERIOR VIEW, SETTING LARGE CORE WITH ASSISTANCE FROM THE OVERHEAD RAIL CRANE IN BOX FLOOR MOLD AREA (WORKERS: DAN T. WELLS AND TRUMAN CARLISLE). - Stockham Pipe & Fittings Company, Ductile Iron Foundry, 4000 Tenth Avenue North, Birmingham, Jefferson County, AL

  9. 12. Interior view, grain tanks (bins). Profile view of overhead ...

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

    12. Interior view, grain tanks (bins). Profile view of overhead (fill) conveyor gallery bridge extending through tops of tanks just below roofs. - Saint Anthony Elevator No. 3, 620 Malcom Avenue, Southeast, Minneapolis, Hennepin County, MN

  10. 35. OVERHEAD VIEW OF VIVIANNA WORKS ORE BIN LOOKING NORTHEAST. ...

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

    35. OVERHEAD VIEW OF VIVIANNA WORKS ORE BIN LOOKING NORTHEAST. GENERATOR BUILDING TOP LEFT, OFFICE AND STOREROOM TOP CENTER, ROTARY KILN AND CONDENSER PLATFORM RIGHT. - Mariscal Quicksilver Mine & Reduction Works, Terlingua, Brewster County, TX

  11. OVERHEAD VIEW OF VIVIANNA WORKS ORE BIN LOOKING NORTHEAST. GENERATOR ...

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

    OVERHEAD VIEW OF VIVIANNA WORKS ORE BIN LOOKING NORTHEAST. GENERATOR BUILDING TOP LEFT, OFFICE AND STOREROOM TOP CENTER, ROTARY KILN AND CONDENSER PLATFORM RIGHT. - Mariscal Quicksilver Mine & Reduction Works, Terlingua, Brewster County, TX

  12. 24. OVERHEAD VIEW OF MARISCAL WORKS ORE BIN FOUNDATION AND ...

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

    24. OVERHEAD VIEW OF MARISCAL WORKS ORE BIN FOUNDATION AND CONDENSERS, TOWARD WHERE ORE DELIVERY TRACK WOULD HAVE RUN, LOOKING NORTHEAST. - Mariscal Quicksilver Mine & Reduction Works, Terlingua, Brewster County, TX

  13. OVERHEAD VIEW OF MARISCAL WORKS ORE BIN FOUNDATION AND CONDENSERS, ...

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

    OVERHEAD VIEW OF MARISCAL WORKS ORE BIN FOUNDATION AND CONDENSERS, TOWARD WHERE ORE DELIVERY TRACK WOULD HAVE RUN, LOOKING NORTHEAST. - Mariscal Quicksilver Mine & Reduction Works, Terlingua, Brewster County, TX

  14. GENERAL OVERHEAD VIEW OF MARISCAL WORKS, SHOWING ORE BIN, LEFT, ...

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

    GENERAL OVERHEAD VIEW OF MARISCAL WORKS, SHOWING ORE BIN, LEFT, CONDENSERS, CENTER, AND CIRCULAR REDWOOD TANK PLATFORMS, RIGHT, LOOKING EAST, NORTHEAST. - Mariscal Quicksilver Mine & Reduction Works, Terlingua, Brewster County, TX

  15. 22. GENERAL OVERHEAD VIEW OF MARISCAL WORKS, SHOWING ORE BIN, ...

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

    22. GENERAL OVERHEAD VIEW OF MARISCAL WORKS, SHOWING ORE BIN, LEFT, CONDENSERS, CENTER, AND CIRCULAR REDWOOD TANK PLATFORMS, RIGHT, LOOKING EAST, NORTHEAST. - Mariscal Quicksilver Mine & Reduction Works, Terlingua, Brewster County, TX

  16. 28. SHOWER AND URINALS, OVERHEAD TOILET STRUCTURE ABOVE ROOF PANEL ...

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

    28. SHOWER AND URINALS, OVERHEAD TOILET STRUCTURE ABOVE ROOF PANEL STORAGE AREA. VIEW TO SOUTH-SOUTHWEST. - Ford Motor Company Long Beach Assembly Plant, Assembly Building, 700 Henry Ford Avenue, Long Beach, Los Angeles County, CA

  17. 27. OVERHEAD TOILET, SHOWER, CHANGE ROOM STRUCTURE. VIEW TO NORTHNORTHEAST. ...

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

    27. OVERHEAD TOILET, SHOWER, CHANGE ROOM STRUCTURE. VIEW TO NORTH-NORTHEAST. - Ford Motor Company Long Beach Assembly Plant, Assembly Building, 700 Henry Ford Avenue, Long Beach, Los Angeles County, CA

  18. 16. VIEW OF OVERHEAD DOOR TO HOP DRYER NO. 3. ...

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

    16. VIEW OF OVERHEAD DOOR TO HOP DRYER NO. 3. ALL EIGHT HOP DRYERS ARE ON THE SECOND FLOOR. - James W. Seavey Hop Driers, 0.6 mile East from junction of Highway 99 & Alexander Avenue, Corvallis, Benton County, OR

  19. 9. VIEW SOUTH OF TURBINE ROOM INTERIOR, WITH OVERHEAD CRANE; ...

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

    9. VIEW SOUTH OF TURBINE ROOM INTERIOR, WITH OVERHEAD CRANE; ABANDONED ARMATURES IN CENTER FOREGROUND; BUS PANEL REMAINS AT LOWER RIGHT CENTER - Turners Falls Power & Electric Company, Hampden Station, East bank of Connecticut River, Chicopee, Hampden County, MA

  20. New rain shed (Building No. 241), overhead pipeline and raw ...

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

    New rain shed (Building No. 241), overhead pipeline and raw water tank T4. Distribution pump house can be seen at the center of building. - Hawaii Volcanoes National Park Water Collection System, Hawaii Volcanoes National Park, Volcano, Hawaii County, HI

  1. 2. OVERHEAD CHEMICAL PROCESS PIPING BETWEEN BUILDINGS 422, ON RIGHT, ...

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

    2. OVERHEAD CHEMICAL PROCESS PIPING BETWEEN BUILDINGS 422, ON RIGHT, AND 431, ON LEFT. - Rocky Mountain Arsenal, Crude Mustard & Aldrin Manufacturing, 1200 feet South of December Seventh Avenue; 600 feet East of D Street, Commerce City, Adams County, CO

  2. 59. SECOND FLOOR, STEEL OVERHEAD CONVEYOR SUPPORT FRAMEWORK ABUTTING FOOTBRIDGE, ...

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

    59. SECOND FLOOR, STEEL OVERHEAD CONVEYOR SUPPORT FRAMEWORK ABUTTING FOOTBRIDGE, BAY 18, TO SOUTHEAST - Ford Motor Company Edgewater Assembly Plant, Assembly Building, 309 River Road, Edgewater, Bergen County, NJ

  3. Southeast corner with overhead crane in foreground Bureau of ...

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

    Southeast corner with overhead crane in foreground - Bureau of Mines Boulder City Experimental Station, Titanium Development Plant, Date Street north of U.S. Highway 93, Boulder City, Clark County, NV

  4. Detail, east side, north end, showing door and overhead rail ...

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

    Detail, east side, north end, showing door and overhead rail for refrigeration room. - Fitzsimons General Hospital, Ice Plant, Southwest Corner of East I Avenue & North Thirteenth Street, Aurora, Adams County, CO

  5. 7. VIEW SHOWING EAST ELEVATION OF OVERHEAD BRIDGE CONNECTING NAPPING ...

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

    7. VIEW SHOWING EAST ELEVATION OF OVERHEAD BRIDGE CONNECTING NAPPING BUILDING (LEFT) WITH CLOTH ROOM (RIGHT), LOOKING WEST - Massachusetts Mills, Cloth Room-Section 15, 95 Bridge Street, Lowell, Middlesex County, MA

  6. Overhead Projector Demonstrations: A Classroom Demonstration of Aliphatic Substitution.

    ERIC Educational Resources Information Center

    Perina, Ivo; Mihanovic, Branka

    1989-01-01

    Presents a halogen substitution of an alkane using a compartmentalized Petri dish or Conway dish on an overhead projector. Provides methodology and several modifications for different reactions. Uses hexane, methyl orange, bromine, and silver nitrate. (MVL)

  7. Childhood cancer and overhead powerlines: a case-control study.

    PubMed Central

    Myers, A.; Clayden, A. D.; Cartwright, R. A.; Cartwright, S. C.

    1990-01-01

    A case-control study has been carried out to examine the occurrence of childhood cancer in relation to the proximity of overhead power lines to a child's home address at birth and to the calculated magnetic field at the address. The study included 374 cases diagnosed in the Yorkshire Health Region between 1970 and 1979, together with 588 matched controls. Magnetic-field strengths at the birth addresses due to the load currents of overhead power lines were calculated on the basis of line-network maps and load records. The results indicate no association between the occurrence of childhood malignancies and either the proximity or the magnetic fields of overhead lines, although the statistical power of the study was limited by the small numbers of children living close to overhead power lines. PMID:2257204

  8. Overhead Projector Demonstrations: Tilted TOPS: Inclined Plane Projection.

    ERIC Educational Resources Information Center

    Alyea, Hubert N.

    1989-01-01

    The construction and uses of a device to facilitate the use of an overhead projector to show chemical reactions is presented. Materials and instructions for construction as well as reactor vessels are discussed. (CW)

  9. INTERIOR VIEW OF SHED, SHOWING STRUCTURAL SYSTEM AND OVERHEAD DOOR ...

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

    INTERIOR VIEW OF SHED, SHOWING STRUCTURAL SYSTEM AND OVERHEAD DOOR MOUNTING, LOOKING NORTHEAST - Marvine Colliery, Shed, West side Boulevard Avenue, between East Parker Street & Route 380, Scranton, Lackawanna County, PA

  10. WEST ELEVATION, CAMERA FACING EAST. THE OVERHEAD PIPES ARE FOR ...

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

    WEST ELEVATION, CAMERA FACING EAST. THE OVERHEAD PIPES ARE FOR DISTRIBUTING STEAM FROM THE NEARBY HEATING PLANT TO VARIOUS PARTS OF THE COMPLEX. - New Haven Rail Yard, Oil Storage Building, Vicinity of Union Avenue, New Haven, New Haven County, CT

  11. 13. TURNING DEVICE SUSPENDED FROM, AND LIFTED BY THE OVERHEAD ...

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

    13. TURNING DEVICE SUSPENDED FROM, AND LIFTED BY THE OVERHEAD CRANE SYSTEM EAST OF No. 1 PRESS. - U.S. Steel Homestead Works, Press Shop No. 1, Along Monongahela River, Homestead, Allegheny County, PA

  12. 7. Ball mill area and second level entry with overhead ...

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

    7. Ball mill area and second level entry with overhead crane in background - Bureau of Mines Boulder City Experimental Station, Ore Dressing Pilot Plant, Date Street north of U.S. Highway 93, Boulder City, Clark County, NV

  13. Independent movement of the voltage sensors in KV2.1/KV6.4 heterotetramers

    PubMed Central

    Bocksteins, Elke; Snyders, Dirk J.; Holmgren, Miguel

    2017-01-01

    Heterotetramer voltage-gated K+ (KV) channels KV2.1/KV6.4 display a gating charge-voltage (QV) distribution composed by two separate components. We use state dependent chemical accessibility to cysteines substituted in either KV2.1 or KV6.4 to assess the voltage sensor movements of each subunit. By comparing the voltage dependences of chemical modification and gating charge displacement, here we show that each gating charge component corresponds to a specific subunit forming the heterotetramer. The voltage sensors from KV6.4 subunits move at more negative potentials than the voltage sensors belonging to KV2.1 subunits. These results indicate that the voltage sensors from the tetrameric channels move independently. In addition, our data shows that 75% of the total charge is attributed to KV2.1, while 25% to KV6.4. Thus, the most parsimonious model for KV2.1/KV6.4 channels’ stoichiometry is 3:1. PMID:28139741

  14. Big George to Carter Mountain 115-kV transmission line project, Park and Hot Springs Counties, Wyoming. Environmental Assessment

    SciTech Connect

    Not Available

    1994-02-01

    The Western Area Power Administration (Western) is proposing to rebuild, operate, and maintain a 115-kilovolt (kV) transmission line between the Big George and Carter Mountain Substations in northwest Wyoming (Park and Hot Springs Counties). This environmental assessment (EA) was prepared in compliance with the National Environmental Policy Act (NEPA) and the regulations of the Council on Environmental Quality (CEQ) and the Department of Energy (DOE). The existing Big George to Carter Mountain 69-kV transmission line was constructed in 1941 by the US Department of Interior, Bureau of Reclamation, with 1/0 copper conductor on wood-pole H-frame structures without an overhead ground wire. The line should be replaced because of the deteriorated condition of the wood-pole H-frame structures. Because the line lacks an overhead ground wire, it is subject to numerous outages caused by lightning. The line will be 54 years old in 1995, which is the target date for line replacement. The normal service life of a wood-pole line is 45 years. Under the No Action Alternative, no new transmission lines would be built in the project area. The existing 69-kV transmission line would continue to operate with routine maintenance, with no provisions made for replacement.

  15. 16. THE INSTALLATION OF CONVEYORS AND OVERHEAD RAILS ELIMINATED THE ...

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

    16. THE INSTALLATION OF CONVEYORS AND OVERHEAD RAILS ELIMINATED THE NEED TO LAY MOLDS OUT ON FLOORS AND HAND-POUR THEM. INSTEAD, WORKERS PULLED LARGE LADLES ALONG OVERHEAD RAILS AND FILLED CONVEYOR-DRIVEN MOLDS WHILE THEY STOOD ON A MOVING PLATFORM THAT TRAVELED AT THE SAME SPEED AS THE MOLD CONVEYOR, CA. 1950. - Stockham Pipe & Fittings Company, 4000 Tenth Avenue North, Birmingham, Jefferson County, AL

  16. Shoulder problems in overhead sports. Part I - biomechanics of throwing.

    PubMed

    Kaczmarek, Piotr Krzysztof; Lubiatowski, Przemysław; Cisowski, Paweł; Grygorowicz, Monika; Łepski, Marcin; Długosz, Jan; Ogrodowicz, Piotr; Dudziński, Witold; Nowak, Maciej; Romanowski, Leszek

    2014-05-15

    The article discusses the biomechanical processes that occur during an overhead throw. This activity is highly specialized and requires full and proper function from the shoulder joint. It consists of active and passive stabilization and synchronous work of the accelerating and decelerating muscles. The process of the overhead throw can be divided into several phases that differ from each other in biomechanical parameters and involvement of specific muscles.

  17. Computer-based mechanical design of overhead lines

    NASA Astrophysics Data System (ADS)

    Rusinaru, D.; Bratu, C.; Dinu, R. C.; Manescu, L. G.

    2016-02-01

    Beside the performance, the safety level according to the actual standards is a compulsory condition for distribution grids’ operation. Some of the measures leading to improvement of the overhead lines reliability ask for installations’ modernization. The constraints imposed to the new lines components refer to the technical aspects as thermal stress or voltage drop, and look for economic efficiency, too. The mechanical sizing of the overhead lines is after all an optimization problem. More precisely, the task in designing of the overhead line profile is to size poles, cross-arms and stays and locate poles along a line route so that the total costs of the line's structure to be minimized and the technical and safety constraints to be fulfilled.The authors present in this paper an application for the Computer-Based Mechanical Design of the Overhead Lines and the features of the corresponding Visual Basic program, adjusted to the distribution lines. The constraints of the optimization problem are adjusted to the existing weather and loading conditions of Romania. The outputs of the software application for mechanical design of overhead lines are: the list of components chosen for the line: poles, cross-arms, stays; the list of conductor tension and forces for each pole, cross-arm and stay for different weather conditions; the line profile drawings.The main features of the mechanical overhead lines design software are interactivity, local optimization function and high-level user-interface

  18. A Study of Electromagnetic Radiation of Corona Discharge Near 500-Kv Electric Installations

    SciTech Connect

    Korzhov, A. V.; Okrainskaya, I. S.; Sidorov, A. I.; Kufel'd, V. D.

    2004-01-15

    Data on the spectral composition and intensity of electromagnetic radiation of corona discharge are obtained in an experimental study performed on the outdoor switchgear of the Shagol 500-kV substation of the Chelyabinsk Enterprise of Trunk Transmission Grids and under a 500-kV Shagol - Kozyrevo overhead transmission line. The electromagnetic environment on the territory of the 500-kV outdoor switchgear is shown to be determined by narrow-band radiations (harmonics of the frequency of electric supply) and wide-band radiations due to corona discharges of high-voltage sources. This means that the personnel experience the action of a commercial-frequency electric field and electromagnetic radiation of a quite wide range, which is not allowed for by the existing guidelines. It is recommended to continue the study in cooperation with medical institutions in order to create guidelines that would allow for the joint action of commercial-frequency electric field and electromagnetic radiation and for the voltage in the line, the current load, the meteorological situation, and other factors.

  19. The voltage-dependent K(+) channels Kv1.3 and Kv1.5 in human cancer.

    PubMed

    Comes, Núria; Bielanska, Joanna; Vallejo-Gracia, Albert; Serrano-Albarrás, Antonio; Marruecos, Laura; Gómez, Diana; Soler, Concepció; Condom, Enric; Ramón Y Cajal, Santiago; Hernández-Losa, Javier; Ferreres, Joan C; Felipe, Antonio

    2013-10-10

    Voltage-dependent K(+) channels (Kv) are involved in a number of physiological processes, including immunomodulation, cell volume regulation, apoptosis as well as differentiation. Some Kv channels participate in the proliferation and migration of normal and tumor cells, contributing to metastasis. Altered expression of Kv1.3 and Kv1.5 channels has been found in several types of tumors and cancer cells. In general, while the expression of Kv1.3 apparently exhibits no clear pattern, Kv1.5 is induced in many of the analyzed metastatic tissues. Interestingly, evidence indicates that Kv1.5 channel shows inversed correlation with malignancy in some gliomas and non-Hodgkin's lymphomas. However, Kv1.3 and Kv1.5 are similarly remodeled in some cancers. For instance, expression of Kv1.3 and Kv1.5 correlates with a certain grade of tumorigenicity in muscle sarcomas. Differential remodeling of Kv1.3 and Kv1.5 expression in human cancers may indicate their role in tumor growth and their importance as potential tumor markers. However, despite of this increasing body of information, which considers Kv1.3 and Kv1.5 as emerging tumoral markers, further research must be performed to reach any conclusion. In this review, we summarize what it has been lately documented about Kv1.3 and Kv1.5 channels in human cancer.

  20. The voltage-dependent K+ channels Kv1.3 and Kv1.5 in human cancer

    PubMed Central

    Comes, Núria; Bielanska, Joanna; Vallejo-Gracia, Albert; Serrano-Albarrás, Antonio; Marruecos, Laura; Gómez, Diana; Soler, Concepció; Condom, Enric; Ramón y Cajal, Santiago; Hernández-Losa, Javier; Ferreres, Joan C.; Felipe, Antonio

    2013-01-01

    Voltage-dependent K+ channels (Kv) are involved in a number of physiological processes, including immunomodulation, cell volume regulation, apoptosis as well as differentiation. Some Kv channels participate in the proliferation and migration of normal and tumor cells, contributing to metastasis. Altered expression of Kv1.3 and Kv1.5 channels has been found in several types of tumors and cancer cells. In general, while the expression of Kv1.3 apparently exhibits no clear pattern, Kv1.5 is induced in many of the analyzed metastatic tissues. Interestingly, evidence indicates that Kv1.5 channel shows inversed correlation with malignancy in some gliomas and non-Hodgkin's lymphomas. However, Kv1.3 and Kv1.5 are similarly remodeled in some cancers. For instance, expression of Kv1.3 and Kv1.5 correlates with a certain grade of tumorigenicity in muscle sarcomas. Differential remodeling of Kv1.3 and Kv1.5 expression in human cancers may indicate their role in tumor growth and their importance as potential tumor markers. However, despite of this increasing body of information, which considers Kv1.3 and Kv1.5 as emerging tumoral markers, further research must be performed to reach any conclusion. In this review, we summarize what it has been lately documented about Kv1.3 and Kv1.5 channels in human cancer. PMID:24133455

  1. A Reference Model for Virtual Machine Launching Overhead

    SciTech Connect

    Wu, Hao; Ren, Shangping; Garzoglio, Gabriele; Timm, Steven; Bernabeu, Gerard; Chadwick, Keith; Noh, Seo-Young

    2014-01-01

    Cloud bursting is one of the key research topics in the cloud computing communities. A well designed cloud bursting module enables private clouds to automatically launch virtual machines (VMs) to public clouds when more resources are needed. One of the main challenges in developing a cloud bursting module is to decide when and where to launch a VM so that all resources are most effectively and efficiently utilized and the system performance is optimized. However, based on system operational data obtained from FermiCloud, a private cloud developed by the Fermi National Accelerator Laboratory for scientific workflows, the VM launching overhead is not a constant. It varies with physical resource utilization, such as CPU and I/O device utilizations, at the time when a VM is launched. Hence, to make judicious decisions as to when and where a VM should be launched, a VM launching overhead reference model is needed. In this paper, we first develop a VM launching overhead reference model based on operational data we have obtained on FermiCloud. Second, we apply the developed reference model on FermiCloud and compare calculated VM launching overhead values based on the model with measured overhead values on FermiCloud. Our empirical results on FermiCloud indicate that the developed reference model is accurate. We believe, with the guidance of the developed reference model, efficient resource allocation algorithms can be developed for cloud bursting process to minimize the operational cost and resource waste.

  2. Ergonomic Assessment of Floor-based and Overhead Lifts

    PubMed Central

    Waters, Thomas R.; Dick, Robert; Lowe, Brian; Werren, Dwight; Parsons, Kelley

    2015-01-01

    Manual full-body vertical lifts of patients have high risk for developing musculoskeletal disorders. Two primary types of battery-powered lift assist devices are available for these tasks: floor-based and overhead-mounted devices. Studies suggest that the operation of floor-based devices may require excessive pushing and pulling forces and that overhead-mounted devices are safer and require lower operating forces. This study evaluated required operating hand forces and resulting biomechanical spinal loading for overhead-mounted lifts versus floor-based lifts across various floor surfaces and patient weight conditions. We did not examine differences in how operators performed the tasks, but rather focused on differences in required operating forces and estimated biomechanical loads across various exposure conditions for a typical operator. Findings show that the floor-based lifts exceeded recommended exposure limits for pushing and pulling for many of the floor/weight conditions and that the overhead-mounted lifts did not. As expected, forces and spinal loads were greater for nonlinoleum floor surfaces compared with linoleum floors. Based on these findings, it is suggested that overhead-mounted devices be used whenever possible, particularly in instances where carpeted floors would be encountered. PMID:26550545

  3. CURRENT CONCEPTS IN SHOULDER EXAMINATION OF THE OVERHEAD ATHLETE

    PubMed Central

    Ellenbecker, Todd

    2013-01-01

    Examination of the shoulder complex has long been described as challenging. This is particularly true in the examination of the overhead athlete who has structural differences when compared to a shoulder patient who is a non‐athlete. Complexity with the examination is due to unique biomechanical and structural changes, multiple joint articulations, multiple pain patterns, and the potential of injury to structures both inside (intra‐articular) and outside (extra‐articular) the glenohumeral joint. Repetitive stresses placed on the shoulders of overhead athletes may affect range of motion, strength, scapular position, and ultimately, the integrity of soft tissue and bony structures in any of the joints that comprise the shoulder complex. Furthermore, many shoulder examination tests thought to be unique to a single structure, joint, or condition can be positive in multiple conditions. The examination of the overhead athletes shoulder, coupled with a thorough medical history will provide a solid foundation to allow a functional physical therapy diagnosis and provide clues as to the presence of the lesion (s) causing disability. The purpose of this clinical commentary is to assist the reader to understand the unique physical characteristics of the overhead athlete, which will lead to a more accurate and reproducible evaluation of athletes who sustain injuries while participating in overhead sports. Level of Evidence: 5 PMID:24175138

  4. Modeling Spatial Dependencies in High-Resolution Overhead Imagery

    SciTech Connect

    Cheriyadat, Anil M; Bright, Eddie A; Vatsavai, Raju

    2011-01-01

    Human settlement regions with different physical and socio-economic attributes exhibit unique spatial characteristics that are often illustrated in high-resolution overhead imageries. For example- size, shape and spatial arrangements of man-made structures are key attributes that vary with respect to the socioeconomic profile of the neighborhood. Successfully modeling these attributes is crucial in developing advanced image understanding systems for interpreting complex aerial scenes. In this paper we present three different approaches to model the spatial context in the overhead imagery. First, we show that the frequency domain of the image can be used to model the spatial context [1]. The shape of the spectral energy contours characterize the scene context and can be exploited as global features. Secondly, we explore a discriminative framework based on the Conditional Random Fields (CRF) [2] to model the spatial context in the overhead imagery. The features derived from the edge orientation distribution calculated for a neighborhood and the associated class labels are used as input features to model the spatial context. Our third approach is based on grouping spatially connected pixels based on the low-level edge primitives to form support-regions [3]. The statistical parameters generated from the support-region feature distributions characterize different geospatial neighborhoods. We apply our approaches on high-resolution overhead imageries. We show that proposed approaches characterize the spatial context in overhead imageries.

  5. Conserved Negative Charges in the N-terminal Tetramerization Domain Mediate Efficient Assembly of Kv2.1 and Kv2.1/Kv6.4 Channels*

    PubMed Central

    Bocksteins, Elke; Labro, Alain J.; Mayeur, Evy; Bruyns, Tine; Timmermans, Jean-Pierre; Adriaensen, Dirk; Snyders, Dirk J.

    2009-01-01

    Voltage-gated potassium (Kv) channels are transmembrane tetramers of individual α-subunits. Eight different Shaker-related Kv subfamilies have been identified in which the tetramerization domain T1, located on the intracellular N terminus, facilitates and controls the assembly of both homo- and heterotetrameric channels. Only the Kv2 α-subunits are able to form heterotetramers with members of the silent Kv subfamilies (Kv5, Kv6, Kv8, and Kv9). The T1 domain contains two subdomains, A and B box, which presumably determine subfamily specificity by preventing incompatible subunits to assemble. In contrast, little is known about the involvement of the A/B linker sequence. Both Kv2 and silent Kv subfamilies contain a fully conserved and negatively charged sequence (CDD) in this linker that is lacking in the other subfamilies. Neutralizing these aspartates in Kv2.1 by mutating them to alanines did not affect the gating properties, but reduced the current density moderately. However, charge reversal arginine substitutions strongly reduced the current density of these homotetrameric mutant Kv2.1 channels and immunocytochemistry confirmed the reduced expression at the plasma membrane. Förster resonance energy transfer measurements using confocal microscopy showed that the latter was not due to impaired trafficking, but to a failure to assemble the tetramer. This was further confirmed with co-immunoprecipitation experiments. The corresponding arginine substitution in Kv6.4 prevented its heterotetrameric interaction with Kv2.1. These results indicate that these aspartates (especially the first one) in the A/B box linker of the T1 domain are required for efficient assembly of both homotetrameric Kv2.1 and heterotetrameric Kv2.1/silent Kv6.4 channels. PMID:19717558

  6. Assessment of electromagnetic field levels from surrounding high-tension overhead power lines for proposed land use.

    PubMed

    Al-Bassam, E; Elumalai, A; Khan, A; Al-Awadi, L

    2016-05-01

    The surrounding outdoor environment for new development has a big effect on the indoor quality of life. The main aim of this work was to determine the suitability of the area for building new schools with reference to electromagnetic field (EMF) effects. The specific objective of this study was to detect the safe distance from the EMF posed by the high-tension overhead power lines in the vicinity of the specified area. The measurements were taken for both the electric and magnetic fields in different months in order to detect the highest EMF levels during the peak power load season. EMDEX II with E-probe and EMDEX II with Linda were used for the measurements. These instruments were all calibrated by ENERTECH Company in USA. The EMF associated with high tension transmission lines that surrounded the proposed site has to be below 0.2 μT (Italian EMF regulations are the most suitable regulations for the establishment of schools in Kuwait). The safety clearance distance from the existing 300-kV high-tension power line has been assigned as 200 m and from other existing 132-kV high-tension power line was 50 m. The proposed site with its predefined boundaries has a magnetic field below the Italian EMF regulations for the establishment of new schools.

  7. Redistribution of Kv1 and Kv7 enhances neuronal excitability during structural axon initial segment plasticity

    PubMed Central

    Kuba, Hiroshi; Yamada, Rei; Ishiguro, Go; Adachi, Ryota

    2015-01-01

    Structural plasticity of the axon initial segment (AIS), the trigger zone of neurons, is a powerful means for regulating neuronal activity. Here, we show that AIS plasticity is not limited to structural changes; it also occurs as changes in ion-channel expression, which substantially augments the efficacy of regulation. In the avian cochlear nucleus, depriving afferent inputs by removing cochlea elongated the AIS, and simultaneously switched the dominant Kv channels at the AIS from Kv1.1 to Kv7.2. Due to the slow activation kinetics of Kv7.2, the redistribution of the Kv channels reduced the shunting conductance at the elongated AIS during the initiation of action potentials and effectively enhanced the excitability of the deprived neurons. The results indicate that the functional plasticity of the AIS works cooperatively with the structural plasticity and compensates for the loss of afferent inputs to maintain the homeostasis of auditory circuits after hearing loss by cochlea removal. PMID:26581625

  8. 13. Emplacement no. 2, overhead view of counterweight well, showing ...

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

    13. Emplacement no. 2, overhead view of counterweight well, showing channel for gun motor cable and bolt plates upon which base ring of gun carriage was mounted - Fort Wadsworth Battery Romeyn B. Ayers, South side of Ayers Road, Staten Island, Rosebank, Richmond County, NY

  9. View east from western edge of complex. Collapsed overhead conveyor ...

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

    View east from western edge of complex. Collapsed overhead conveyor in foreground carried ganister down to the brickyard from crushing and grinding facility on the mountain. - Harbison-Walker Refractories Company, West end of Shirley Street, Mount Union, Huntingdon County, PA

  10. Phase Sensitive Cueing for 3D Objects in Overhead Images

    SciTech Connect

    Paglieroni, D

    2005-02-04

    Locating specific 3D objects in overhead images is an important problem in many remote sensing applications. 3D objects may contain either one connected component or multiple disconnected components. Solutions must accommodate images acquired with diverse sensors at various times of the day, in various seasons of the year, or under various weather conditions. Moreover, the physical manifestation of a 3D object with fixed physical dimensions in an overhead image is highly dependent on object physical dimensions, object position/orientation, image spatial resolution, and imaging geometry (e.g., obliqueness). This paper describes a two-stage computer-assisted approach for locating 3D objects in overhead images. In the matching stage, the computer matches models of 3D objects to overhead images. The strongest degree of match over all object orientations is computed at each pixel. Unambiguous local maxima in the degree of match as a function of pixel location are then found. In the cueing stage, the computer sorts image thumbnails in descending order of figure-of-merit and presents them to human analysts for visual inspection and interpretation. The figure-of-merit associated with an image thumbnail is computed from the degrees of match to a 3D object model associated with unambiguous local maxima that lie within the thumbnail. This form of computer assistance is invaluable when most of the relevant thumbnails are highly ranked, and the amount of inspection time needed is much less for the highly ranked thumbnails than for images as a whole.

  11. 19. Interior view showing flight simulator partition and rear overhead ...

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

    19. Interior view showing flight simulator partition and rear overhead door, dock no. 493. View to south. - Offutt Air Force Base, Looking Glass Airborne Command Post, Nose Docks, On either side of Hangar Access Apron at Northwest end of Project Looking Glass Historic District, Bellevue, Sarpy County, NE

  12. MOBILE LADLES, ATTACHED TO OVERHEAD RAILS, ARE FILLED AT EITHER ...

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

    MOBILE LADLES, ATTACHED TO OVERHEAD RAILS, ARE FILLED AT EITHER THE MALLEABLE FOUNDRY BULL LADLE OR ELECTRIC FURNACE BEFORE THEY TRANSPORT MOLTEN IRON TO MOLDS PREPARED BY DISAMATIC MOLDMAKING MACHINE OR ON ONE OF THE CONVEYORS. - Stockham Pipe & Fittings Company, Malleable Foundry, 4000 Tenth Avenue North, Birmingham, Jefferson County, AL

  13. GRINDING ROOM, LOOKING EAST. NOTE OVERHEAD BRIDGE CRANE RIDING ON ...

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

    GRINDING ROOM, LOOKING EAST. NOTE OVERHEAD BRIDGE CRANE RIDING ON STEEL RAILS SUPPORTED BY WOODEN BEAMS AND CYCLONE CLASSIFIER IN CENTER. AT RIGHT IS TOP PORTION OF FLASH FLOTATION CELL. - Shenandoah-Dives Mill, 135 County Road 2, Silverton, San Juan County, CO

  14. Dissolving Carboxylic Acids and Primary Amines on the Overhead Projector

    ERIC Educational Resources Information Center

    Solomon, Sally D.; Rutkowsky, Susan A.

    2010-01-01

    Liquid carboxylic acids (or primary amines) with limited solubility in water are dissolved by addition of aqueous sodium hydroxide (or hydrochloric acid) on the stage of an overhead projector using simple glassware and very small quantities of chemicals. This effective and colorful demonstration can be used to accompany discussions of the…

  15. The Overhead Projector and the Teacher of English in Brazil.

    ERIC Educational Resources Information Center

    Funck, Elvio Antonio

    This paper presents arguments for the consistent use of modern audiovisual aids in English classes, not as a complementary device, but as a fundamental aid. The intention of the thesis is to: (1) show that the overhead projector can be used to help students develop the four language skills; and (2) encourage English teachers, particularly in…

  16. Oblique view to the northwest detailing four overhead rolling doors ...

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

    Oblique view to the northwest detailing four overhead rolling doors on the northeast elevation - Over-the-Horizon Backscatter Radar Network, Mountain Home Air Force Operations Building, On Desert Street at 9th Avenue Mountain Home Air Force Base, Mountain Home, Elmore County, ID

  17. 78 FR 77027 - Overhead Clearance (Air-Draft) Accidents

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-20

    ... address the problem of overhead clearance (air-draft) accidents. In its petition, which calls for vessel... methods: (1) Federal eRulemaking Portal: http://www.regulations.gov . (2) Fax: 202-493-2251. (3) Mail..., ] contact LCDR William Nabach, Office of Vessel and Facility Operating Standards (CG-OES-2), U.S....

  18. A Simple Polarimeter and Experiments Utilizing an Overhead Projector.

    ERIC Educational Resources Information Center

    Dorn, H. C.; And Others

    1984-01-01

    Although polarimeters that illustrate rotation of plane-polarized light by chiral solutions have been previously described, the polarimeter described in this paper has certain advantages when used in conjunction with an overhead projector. Instructions for constructing this polarimeter and its use in demonstrating the optical activity of sugars…

  19. The Overhead System: Production, Implementation and Utilization. 2nd Edition.

    ERIC Educational Resources Information Center

    Smith, Richard E.; Pearson, Jerry D.

    This handbook is designed to help three groups: the administrator who does not have the services of a media specialist, the media specialist who wishes to expand his knowledge or skills, and the classroom teacher who recognizes the value of the overhead as a teaching tool and is looking for practical assistance. Guidelines are provided in 11…

  20. 18. PRIOR TO THE USE OF CONVEYORS AND OVERHEAD RAILS, ...

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

    18. PRIOR TO THE USE OF CONVEYORS AND OVERHEAD RAILS, MOLDERS, USUALLY AFRICAN-AMERICAN, HAD TO INDIVIDUALLY HAND FILL MOLDS LAID OUT ON THE FLOOR, SUCH AS THESE IN THE MALLEABLE FOUNDRY IN 1923. - Stockham Pipe & Fittings Company, 4000 Tenth Avenue North, Birmingham, Jefferson County, AL

  1. 5. OVERHEAD VIEW OF GENE CAMP LOOKING SOUTH. GENE PUMP ...

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

    5. OVERHEAD VIEW OF GENE CAMP LOOKING SOUTH. GENE PUMP PLANT IS AT CENTER WITH ADMINISTRATIVE COMPLEX IN FOREGROUND AND RESIDENTIAL AREA BEYOND PLANT. - Gene Pump Plant, South of Gene Wash Reservoir, 2 miles west of Whitsett Pump Plant, Parker Dam, San Bernardino County, CA

  2. Overhead Projector Demonstrations: Some Ideas from the Past.

    ERIC Educational Resources Information Center

    Kolb, Doris

    1987-01-01

    Describes nine chemistry demonstrations that can be done using an overhead projector. Includes demonstrations on common ion effect, crystal formation from supersaturated solutions, making iron positive with nitric acid, optical activity, carbon dioxide in human breath, amphoteric hydroxides, the surface tension of mercury, and natural acid-base…

  3. STOCK YARD LOOKING SOUTHEAST SHOWING OVERHEAD YARD CRANE RAIL, THE ...

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

    STOCK YARD LOOKING SOUTHEAST SHOWING OVERHEAD YARD CRANE RAIL, THE MALLEABLE CUPOLAS AND EMISSION RECOVERY SYSTEM, OLD SHED ROOF THAT COVERED THE EARLIER MALLEABLE CUPOLA CHARGING CRANE, MALLEABLE FOUNDRY, AND POLLUTION CONTROL BAGHOUSE. - Stockham Pipe & Fittings Company, 4000 Tenth Avenue North, Birmingham, Jefferson County, AL

  4. Overhead Projector Spectrum of Polymethine Dye: A Physical Chemistry Demonstration.

    ERIC Educational Resources Information Center

    Solomon, Sally; Hur, Chinhyu

    1995-01-01

    Encourages the incorporation into lecture of live experiments that can be predicted or interpreted with abstract models. A demonstration is described where the position of the predominant peak of 1,1'-diethyl-4,4'-cyanine iodide is measured in class using an overhead projector spectrometer, then predicted using the model of a particle in a…

  5. 12. OVERHEAD VIEW OF THE EVISCERATION AREA; LOOKING NORTH FROM ...

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

    12. OVERHEAD VIEW OF THE EVISCERATION AREA; LOOKING NORTH FROM THE VISITORS' GALLERY; NOTE THE RAISED CONCRETE PLATFORMS FOR WORKERS; VISCERA TABLE HAS BEEN REMOVED - Rath Packing Company, Beef Killing Building, Sycamore Street between Elm & Eighteenth Streets, Waterloo, Black Hawk County, IA

  6. 13. Interior view, grain tanks (bins). Barrel view of overhead ...

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

    13. Interior view, grain tanks (bins). Barrel view of overhead (fill) conveyor gallery bridge extending through tops of tanks just below roofs. Grain tripper straddles belt conveyor at mid-view. - Saint Anthony Elevator No. 3, 620 Malcom Avenue, Southeast, Minneapolis, Hennepin County, MN

  7. 5. Overhead trackandpulley system used to haul materials stored in ...

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

    5. Overhead track-and-pulley system used to haul materials stored in stock bins under Jones Street to the Tender Frame Shop. - Central of Georgia Railway, Savannah Repair Shops & Terminal Facilities, Tender Frame Shop, Bounded by West Broad, Jones, West Boundary & Hull Streets, Savannah, Chatham County, GA

  8. Communication overhead on the Intel iPSC-860 hypercube

    NASA Technical Reports Server (NTRS)

    Bokhari, Shahid H.

    1990-01-01

    Experiments were conducted on the Intel iPSC-860 hypercube in order to evaluate the overhead of interprocessor communication. It is demonstrated that: (1) contrary to popular belief, the distance between two communicating processors has a significant impact on communication time, (2) edge contention can increase communication time by a factor of more than 7, and (3) node contention has no measurable impact.

  9. Prevalence of Scapular Dyskinesis in Overhead and Nonoverhead Athletes

    PubMed Central

    Burn, Matthew B.; McCulloch, Patrick C.; Lintner, David M.; Liberman, Shari R.; Harris, Joshua D.

    2016-01-01

    Background: Scapular dyskinesis, or abnormal dynamic scapular control, is a condition that is commonly associated with shoulder pathology but is also present in asymptomatic individuals. Literature varies on whether it represents a cause or symptom of shoulder pathology, but it is believed to be a risk factor for further injury. Clinical identification focuses on visual observation and examination maneuvers. Treatment of altered scapular motion has been shown to improve shoulder symptoms. It is thought to be more common in overhead athletes due to their reliance on unilateral upper extremity function but the incidence within nonoverhead athletes is unknown. Hypothesis: Overhead athletes will have a greater prevalence of scapular dyskinesis when compared with nonoverhead athletes. Study Design: Systematic review; Level of evidence, 3. Methods: After PROSPERO registration, a systematic review was performed using PRISMA guidelines through the PubMed database looking for studies published before October 2014. All studies containing the search terms scapular, scapulothoracic, dyskinesis, dyskinesia, shoulder athlete, or overhead athlete were included. Studies that did not include prevalence data for scapular dyskinesis were excluded. Study methodological quality was evaluated using the modified Coleman methodology score. Descriptive statistics and 2-proportion 2-tailed z-tests were used to compare the reported prevalence of scapular dyskinesis between overhead and nonoverhead athletes. Results: Twelve studies were analyzed including 1401 athletes (1257 overhead and 144 nonoverhead; mean age, 24.4 ± 7.1 years; 78% men). All the studies were evidence level 2 (33%) or level 3 (67%). The reported prevalence of scapular dyskinesis was significantly (P < .0001) higher in overhead athletes (61%) compared with nonoverhead athletes (33%). Conclusion: Scapular dyskinesis was found to have a greater reported prevalence (61%) in overhead athletes compared with nonoverhead athletes

  10. The neuronal Kv4 channel complex.

    PubMed

    Covarrubias, Manuel; Bhattacharji, Aditya; De Santiago-Castillo, Jose A; Dougherty, Kevin; Kaulin, Yuri A; Na-Phuket, Thanawath Ratanadilok; Wang, Guangyu

    2008-08-01

    Kv4 channel complexes mediate the neuronal somatodendritic A-type K(+) current (I(SA)), which plays pivotal roles in dendritic signal integration. These complexes are composed of pore-forming voltage-gated alpha-subunits (Shal/Kv4) and at least two classes of auxiliary beta-subunits: KChIPs (K(+)-Channel-Interacting-Proteins) and DPLPs (Dipeptidyl-Peptidase-Like-Proteins). Here, we review our investigations of Kv4 gating mechanisms and functional remodeling by specific auxiliary beta-subunits. Namely, we have concluded that: (1) the Kv4 channel complex employs novel alternative mechanisms of closed-state inactivation; (2) the intracellular Zn(2+) site in the T1 domain undergoes a conformational change tightly coupled to voltage-dependent gating and is targeted by nitrosative modulation; and (3) discrete and specific interactions mediate the effects of KChIPs and DPLPs on activation, inactivation and permeation of Kv4 channels. These studies are shedding new light on the molecular bases of I(SA) function and regulation.

  11. KV1 and KV3 Potassium Channels Identified at Presynaptic Terminals of the Corticostriatal Synapses in Rat

    PubMed Central

    Meneses, David; Vega, Ana V.; Torres-Cruz, Francisco Miguel; Barral, Jaime

    2016-01-01

    In the last years it has been increasingly clear that KV-channel activity modulates neurotransmitter release. The subcellular localization and composition of potassium channels are crucial to understanding its influence on neurotransmitter release. To investigate the role of KV in corticostriatal synapses modulation, we combined extracellular recording of population-spike and pharmacological blockage with specific and nonspecific blockers to identify several families of KV channels. We induced paired-pulse facilitation (PPF) and studied the changes in paired-pulse ratio (PPR) before and after the addition of specific KV blockers to determine whether particular KV subtypes were located pre- or postsynaptically. Initially, the presence of KV channels was tested by exposing brain slices to tetraethylammonium or 4-aminopyridine; in both cases we observed a decrease in PPR that was dose dependent. Further experiments with tityustoxin, margatoxin, hongotoxin, agitoxin, dendrotoxin, and BDS-I toxins all rendered a reduction in PPR. In contrast heteropodatoxin and phrixotoxin had no effect. Our results reveal that corticostriatal presynaptic KV channels have a complex stoichiometry, including heterologous combinations KV1.1, KV1.2, KV1.3, and KV1.6 isoforms, as well as KV3.4, but not KV4 channels. The variety of KV channels offers a wide spectrum of possibilities to regulate neurotransmitter release, providing fine-tuning mechanisms to modulate synaptic strength. PMID:27379187

  12. KV1 and KV3 Potassium Channels Identified at Presynaptic Terminals of the Corticostriatal Synapses in Rat.

    PubMed

    Meneses, David; Vega, Ana V; Torres-Cruz, Francisco Miguel; Barral, Jaime

    2016-01-01

    In the last years it has been increasingly clear that KV-channel activity modulates neurotransmitter release. The subcellular localization and composition of potassium channels are crucial to understanding its influence on neurotransmitter release. To investigate the role of KV in corticostriatal synapses modulation, we combined extracellular recording of population-spike and pharmacological blockage with specific and nonspecific blockers to identify several families of KV channels. We induced paired-pulse facilitation (PPF) and studied the changes in paired-pulse ratio (PPR) before and after the addition of specific KV blockers to determine whether particular KV subtypes were located pre- or postsynaptically. Initially, the presence of KV channels was tested by exposing brain slices to tetraethylammonium or 4-aminopyridine; in both cases we observed a decrease in PPR that was dose dependent. Further experiments with tityustoxin, margatoxin, hongotoxin, agitoxin, dendrotoxin, and BDS-I toxins all rendered a reduction in PPR. In contrast heteropodatoxin and phrixotoxin had no effect. Our results reveal that corticostriatal presynaptic KV channels have a complex stoichiometry, including heterologous combinations KV1.1, KV1.2, KV1.3, and KV1.6 isoforms, as well as KV3.4, but not KV4 channels. The variety of KV channels offers a wide spectrum of possibilities to regulate neurotransmitter release, providing fine-tuning mechanisms to modulate synaptic strength.

  13. Moeglichkeiten individualisierter Arbeit mit Hilfe des Overhead-Projektors (Possibilities for Individualized Work with the Aid of the Overhead Projector)

    ERIC Educational Resources Information Center

    Budde, Ulrich

    1975-01-01

    Individualized work in teaching English is highly desirable, and the overhead projector is particularly useful in such work. Three examples of its possibilities are given: Dialog treatment, working with basic ("kernel") texts, and comparison of the simple present, simple past and present perfect tenses. (Text is in German.) (IFS/WGA)

  14. Loss of 115 kV Power

    SciTech Connect

    Smith, J.A.

    2001-08-22

    This report discusses the postulated loss of 115 kV power. Continuous electrical power to Savannah River Plant reactors is necessary to maintain water flow for heat removal and essential monitoring and control. Should power supplied to the plant 115 kV system from offsite be lost, on-site generation is sufficient to maintain all reactors in a safe shutdown mode for an indefinite period. Should on-site generators for the 115 kV grid also be lost, diesel-electric generators within each reactor building are also sufficient to maintain safe shutdown for a finite period. In all cases DC power for necessary monitoring and control would be available from battery systems with AC converter backup.

  15. 30 CFR 57.16015 - Work or travel on overhead crane bridges.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Work or travel on overhead crane bridges. 57... MINES Materials Storage and Handling § 57.16015 Work or travel on overhead crane bridges. No person shall work from or travel on the bridge of an overhead crane unless the bridge is provided...

  16. 30 CFR 57.16015 - Work or travel on overhead crane bridges.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Work or travel on overhead crane bridges. 57... MINES Materials Storage and Handling § 57.16015 Work or travel on overhead crane bridges. No person shall work from or travel on the bridge of an overhead crane unless the bridge is provided...

  17. 30 CFR 57.16015 - Work or travel on overhead crane bridges.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Work or travel on overhead crane bridges. 57... MINES Materials Storage and Handling § 57.16015 Work or travel on overhead crane bridges. No person shall work from or travel on the bridge of an overhead crane unless the bridge is provided...

  18. 30 CFR 56.16015 - Work or travel on overhead crane bridges.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Work or travel on overhead crane bridges. 56... Materials Storage and Handling § 56.16015 Work or travel on overhead crane bridges. No person shall work from or travel on the bridge of an overhead crane unless the bridge is provided with...

  19. 30 CFR 57.16015 - Work or travel on overhead crane bridges.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Work or travel on overhead crane bridges. 57... MINES Materials Storage and Handling § 57.16015 Work or travel on overhead crane bridges. No person shall work from or travel on the bridge of an overhead crane unless the bridge is provided...

  20. 30 CFR 56.16015 - Work or travel on overhead crane bridges.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Work or travel on overhead crane bridges. 56... Materials Storage and Handling § 56.16015 Work or travel on overhead crane bridges. No person shall work from or travel on the bridge of an overhead crane unless the bridge is provided with...

  1. 30 CFR 56.16015 - Work or travel on overhead crane bridges.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Work or travel on overhead crane bridges. 56... Materials Storage and Handling § 56.16015 Work or travel on overhead crane bridges. No person shall work from or travel on the bridge of an overhead crane unless the bridge is provided with...

  2. 30 CFR 56.16015 - Work or travel on overhead crane bridges.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Work or travel on overhead crane bridges. 56... Materials Storage and Handling § 56.16015 Work or travel on overhead crane bridges. No person shall work from or travel on the bridge of an overhead crane unless the bridge is provided with...

  3. 75 FR 81661 - Agency Information Collection Activities; Submission for OMB Review; Comment Request; Overhead...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-28

    ...; Overhead and Gantry Cranes Standard ACTION: Notice. SUMMARY: The Department of Labor (DOL) hereby announces... collection request (ICR) titled, ``Overhead and Gantry Cranes Standard,'' to the Office of Management and... Health Administration (OSHA). Title of Collection: Overhead and Gantry Cranes Standard. OMB...

  4. 30 CFR 57.16015 - Work or travel on overhead crane bridges.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Work or travel on overhead crane bridges. 57... MINES Materials Storage and Handling § 57.16015 Work or travel on overhead crane bridges. No person shall work from or travel on the bridge of an overhead crane unless the bridge is provided...

  5. 30 CFR 56.16015 - Work or travel on overhead crane bridges.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Work or travel on overhead crane bridges. 56... Materials Storage and Handling § 56.16015 Work or travel on overhead crane bridges. No person shall work from or travel on the bridge of an overhead crane unless the bridge is provided with...

  6. Ten Suggestions and One Commandment: Using Overhead Projectors in Geography Classrooms.

    ERIC Educational Resources Information Center

    Gersmehl, Philip J.

    1985-01-01

    Suggestions for effective use of overhead projectors include making images large, preparing standard base maps, making lettering clear, presenting only one idea per overhead, keeping things simple, using only half a page for each image, using the overhead as a chalkboard, using color thoughtfully, making symbols bold, and anticipating emergencies.…

  7. Reducing the overhead for quantum computation when noise is biased

    NASA Astrophysics Data System (ADS)

    Webster, Paul; Bartlett, Stephen D.; Poulin, David

    2015-12-01

    We analyze a model for fault-tolerant quantum computation with low overhead suitable for situations where the noise is biased. The basis for this scheme is a gadget for the fault-tolerant preparation of magic states that enable universal fault-tolerant quantum computation using only Clifford gates that preserve the noise bias. We analyze the distillation of |T > -type magic states using this gadget at the physical level, followed by concatenation with the 15-qubit quantum Reed-Muller code, and comparing our results with standard constructions. In the regime where the noise bias (rate of Pauli Z errors relative to other single-qubit errors) is greater than a factor of 10, our scheme has lower overhead across a broad range of relevant noise rates.

  8. MICROINSTABILITY OF THE SHOULDER IN THE OVERHEAD ATHLETE

    PubMed Central

    Curtis, Alan S.

    2013-01-01

    The overhead throwing athlete is an extremely challenging patient in sports medicine. The repetitive microtraumatic stresses and extreme ranges of motion observed within the athlete’s shoulder joint complex during the throwing motion constantly place the athlete at risk for injury. While gross instability of the shoulder is possible, microinstability is seen far more frequently and is associated with a variety of different pathologies, including rotator cuff tendonitis, internal impingement, and labral lesions. Treatment of the overhead athlete requires the understanding of several principles based on the unique physical characteristics of this type of athlete and the demands placed upon the static stabilizing structures during the act of throwing. The purpose of this paper is to describe these principles and incorporate them into in a multi‐phase progressive rehabilitation program designed to prevent injuries and rehabilitate the injured athlete, both non‐operatively and postoperatively. PMID:24175140

  9. Electromyographic analysis of an ergonomic risk factor: overhead work

    PubMed Central

    Kinali, Gulsah; Kara, Sadık; Yıldırım, Mustafa Selman

    2016-01-01

    [Purpose] Repetitive upper extremity exercises result in overuse injuries. However, it is challenging to identify the specific causative movements. This study evaluated the effects of different shoulder positions on grip and electrophysiological activity of upper extremity muscles. [Subjects and Methods] Forty subjects ranging from 18 and 30 years of age were analyzed. Surface electromyography and hand grip strength were measured during a range of shoulder exercises and numerous signal processing methods were applied. [Results] The maximum electromyographic activity intensity was observed in the wrist extensors at various angles. Deltoid activity rose significantly during shoulder flexion. [Conclusion] Overhead work causes shoulder muscle fatigue and prevents effective hand function, which affects occupational health and efficiency. Overhead work involves a hazardous position and decreases efficiency. Ergonomic solutions should be developed to prevent muscle fatigue and decreased grip force. PMID:27390448

  10. Electromyographic analysis of an ergonomic risk factor: overhead work.

    PubMed

    Kinali, Gulsah; Kara, Sadık; Yıldırım, Mustafa Selman

    2016-06-01

    [Purpose] Repetitive upper extremity exercises result in overuse injuries. However, it is challenging to identify the specific causative movements. This study evaluated the effects of different shoulder positions on grip and electrophysiological activity of upper extremity muscles. [Subjects and Methods] Forty subjects ranging from 18 and 30 years of age were analyzed. Surface electromyography and hand grip strength were measured during a range of shoulder exercises and numerous signal processing methods were applied. [Results] The maximum electromyographic activity intensity was observed in the wrist extensors at various angles. Deltoid activity rose significantly during shoulder flexion. [Conclusion] Overhead work causes shoulder muscle fatigue and prevents effective hand function, which affects occupational health and efficiency. Overhead work involves a hazardous position and decreases efficiency. Ergonomic solutions should be developed to prevent muscle fatigue and decreased grip force.

  11. On-line corrosion control in refinery overhead systems

    SciTech Connect

    Correa, L.A.

    1995-11-01

    Corrosion is one of the great causes of accidents and economic losses in petroleum and petrochemical industries. Crude unit overheads are one of the most corrosion affected parts and large amounts of work and money has been spent on its control and prevention. Thus, new materials, inhibitors and monitoring techniques are constantly under testing in order to improve corrosion prevention and plant reliability. Expert Systems are a rising technology in industrial process monitoring and problem diagnosing. This sort of computer program is developed trying to simulate the human expert intelligent behavior in the task of solving a specific problem. The crude units overhead corrosion control is a hard and time consuming task that seems to be a fruitful field to expert systems application.

  12. Limiting electric fields of HVDC overhead power lines.

    PubMed

    Leitgeb, N

    2014-05-01

    As a consequence of the increased use of renewable energy and the now long distances between energy generation and consumption, in Europe, electric power transfer by high-voltage (HV) direct current (DC) overhead power lines gains increasing importance. Thousands of kilometers of them are going to be built within the next years. However, existing guidelines and regulations do not yet contain recommendations to limit static electric fields, which are one of the most important criteria for HVDC overhead power lines in terms of tower design, span width and ground clearance. Based on theoretical and experimental data, in this article, static electric fields associated with adverse health effects are analysed and various criteria are derived for limiting static electric field strengths.

  13. Overhead-Performance Tradeoffs in Distributed Wireless Networks

    DTIC Science & Technology

    2015-06-26

    time-frequency resources are spent on non-information bearing control information that is not efficiently encoded. Three simple resource controllers...poorly encoded non-information bearing resource measurement and control signals. This enabled the investigators to make a strong case for studying the...between the overhead an optimized distributed wireless network controller collects and the performance on the data- bearing signals it achieves: the more

  14. Passive optical sensor for lightning detection on overhead power lines

    NASA Astrophysics Data System (ADS)

    Rosolem, J. B.; Barbosa, C. F.; Florídia, C.; Bezerra, E. L.

    2009-10-01

    In this work we present the results of a passive optical sensor for monitoring lightning strikes on overhead power lines, which can also be used for several other applications. The optic sensor is very simple and cheap and basically consists in the use of an antenna connected directly to a semiconductor laser. No batteries and solar panels are necessary to implement this sensing system in power lines towers. It was tested in laboratory and showed a good performance.

  15. Glutinous Water. Protecting Vertical and Overhead Surfaces from Fire Spread

    DTIC Science & Technology

    1994-02-28

    DISTRIBUTION CODE Approved for public release; distribution unlimited. 13. ABSTRACT (Maximum 200 words ) Most of the water used in firefighting is not only...Naval Research Laboratory AD-A277 280 Washington, DC 20375-5320 NRL/MR/6180--94-7431 DTIC S ELECTE MAR 24 19941 Glutinous Water F Protecting Vertical...TYPE AND DATES COVERED February 28, 1994 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Glutinous Water Protecting Vertical and Overhead Surfaces From Fire

  16. An estimation of lightning insulation level of overhead distribution lines

    SciTech Connect

    Jacob, P.B.; Grzybowski, S. . Dept. of Electrical Engineering); Ross, E.R. )

    1991-01-01

    This paper develops a practical procedure for determining the total insulation strength of multiple or composite insulations most commonly used in the design of overhead distribution lines. Laboratory test data were obtained on a wide range of combinations and configurations utilizing porcelain, polymer and fiberglass insulators as well as wood poles and wood crossarms. Data were obtained for both dry and wet conditions with positive and negative polarities of the impulses.

  17. Modeling the Virtual Machine Launching Overhead under Fermicloud

    SciTech Connect

    Garzoglio, Gabriele; Wu, Hao; Ren, Shangping; Timm, Steven; Bernabeu, Gerard; Noh, Seo-Young

    2014-11-12

    FermiCloud is a private cloud developed by the Fermi National Accelerator Laboratory for scientific workflows. The Cloud Bursting module of the FermiCloud enables the FermiCloud, when more computational resources are needed, to automatically launch virtual machines to available resources such as public clouds. One of the main challenges in developing the cloud bursting module is to decide when and where to launch a VM so that all resources are most effectively and efficiently utilized and the system performance is optimized. However, based on FermiCloud’s system operational data, the VM launching overhead is not a constant. It varies with physical resource (CPU, memory, I/O device) utilization at the time when a VM is launched. Hence, to make judicious decisions as to when and where a VM should be launched, a VM launch overhead reference model is needed. The paper is to develop a VM launch overhead reference model based on operational data we have obtained on FermiCloud and uses the reference model to guide the cloud bursting process.

  18. Life cycle assessment of overhead and underground primary power distribution.

    PubMed

    Bumby, Sarah; Druzhinina, Ekaterina; Feraldi, Rebe; Werthmann, Danae; Geyer, Roland; Sahl, Jack

    2010-07-15

    Electrical power can be distributed in overhead or underground systems, both of which generate a variety of environmental impacts at all stages of their life cycles. While there is considerable literature discussing the trade-offs between both systems in terms of aesthetics, safety, cost, and reliability, environmental assessments are relatively rare and limited to power cable production and end-of-life management. This paper assesses environmental impacts from overhead and underground medium voltage power distribution systems as they are currently built and managed by Southern California Edison (SCE). It uses process-based life cycle assessment (LCA) according to ISO 14044 (2006) and SCE-specific primary data to the extent possible. Potential environmental impacts have been calculated using a wide range of midpoint indicators, and robustness of the results has been investigated through sensitivity analysis of the most uncertain and potentially significant parameters. The studied underground system has higher environmental impacts in all indicators and for all parameter values, mostly due to its higher material intensity. For both systems and all indicators the majority of impact occurs during cable production. Promising strategies for impact reduction are thus cable failure rate reduction for overhead and cable lifetime extension for underground systems.

  19. Dihydropyridine Ca2+ channel antagonists and agonists block Kv4.2, Kv4.3 and Kv1.4 K+ channels expressed in HEK293 cells.

    PubMed

    Hatano, Noriyuki; Ohya, Susumu; Muraki, Katsuhiko; Giles, Wayne; Imaizumi, Yuji

    2003-06-01

    (1) We have determined the molecular basis of nicardipine-induced block of cardiac transient outward K(+) currents (I(to)). Inhibition of I(to) was studied using cloned voltage-dependent K(+) channels (Kv) channels, rat Kv4.3L, Kv4.2, and Kv1.4, expressed in human embryonic kidney cell line 293 (HEK293) cells. (2) Application of the dihydropyridine Ca(2+) channel antagonist, nicardipine, accelerated the inactivation rate and reduced the peak amplitude of Kv4.3L currents in a concentration-dependent manner (IC(50): 0.42 micro M). The dihydropyridine (DHP) Ca(2+) channel agonist, Bay K 8644, also blocked this K(+) current (IC(50): 1.74 micro M). (3) Nicardipine (1 micro M) slightly, but significantly, shifted the voltage dependence of activation and steady-state inactivation to more negative potentials, and also slowed markedly the recovery from inactivation of Kv4.3L currents. (4) Coexpression of K(+) channel-interacting protein 2 (KChIP2) significantly slowed the inactivation of Kv4.3L currents as expected. However, the features of DHP-induced block of K(+) current were not substantially altered. (5) Nicardipine exhibited similar block of Kv1.4 and Kv4.2 channels stably expressed in HEK293 cells; IC(50)'s were 0.80 and 0.62 micro M, respectively. (6) Thus, at submicromolar concentrations, DHP Ca(2+) antagonist and agonist inhibit Kv4.3L and have similar inhibiting effects on other components of cardiac I(to), Kv4.2 and Kv1.4.

  20. A Kv1.5 to Kv1.3 switch in endogenous hippocampal microglia and a role in proliferation.

    PubMed

    Kotecha, S A; Schlichter, L C

    1999-12-15

    The proliferation of microglia is a normal process in CNS development and in the defense against pathological insults, although, paradoxically, it contributes to several brain diseases. We have examined the types of voltage-activated K(+) currents (Kv) and their roles in microglial proliferation. Microglia were tissue-printed directly from the hippocampal region using brain slices from 5- to 14-d-old rats. Immediately after tissue prints were prepared, unipolar and bipolar microglia expressed a large Kv current, and the cells were not proliferating. Surprisingly, this current was biophysically and pharmacologically distinct from Kv1.3, which has been found in dissociated, cultured microglia, but it was very similar to Kv1.5. After several days in culture the microglia became highly proliferative, and although the Kv prevalence and current density decreased, many cells exhibited a prominent Kv that was indistinguishable from Kv1.3. The Kv1.5-like current was present in nonproliferating cells, whereas proliferating cells expressed the Kv1.3-like current. Immunocytochemical staining showed a dramatic shift in expression and localization of Kv1.3 and Kv1.5 proteins in microglia: Kv1.5 moving away from the surface and Kv1.3 moving to the surface as the cells were cultured. K(+) channel blockers inhibited proliferation, and the pharmacology of this inhibition correlated with the type of Kv current expressed. Our study, which introduces a method for the physiological examination of microglia from identified brain regions, demonstrates the differential expression of two functional Kv subunits and shows that a functional delayed rectifier current is necessary for microglia proliferation.

  1. Functional characterization of Kv channel beta-subunits from rat brain.

    PubMed Central

    Heinemann, S H; Rettig, J; Graack, H R; Pongs, O

    1996-01-01

    1. The potassium channel beta-subunit from rat brain, Kv beta 1.1, is known to induce inactivation of the delayed rectifier channel Kv1.1 and Kv1.4 delta 1-110. 2. Kv beta 1.1 was co-expressed in Xenopus oocytes with various other potassium channel alpha-subunits. Kv beta 1.1 induced inactivation in members of the Kv1 subfamily with the exception of Kv 1.6; no inactivation of Kv 2.1, Kv 3.4 delta 2-28 and Kv4.1 channels could be observed. 3. The second member of the beta-subunit subfamily, Kv beta 2, had a shorter N-terminal end, accelerated inactivation of the A-type channel Kv 1.4, but did not induce inactivation when co-expressed with delayed rectifiers of the Kv1 channel family. 4. To test whether this subunit co-assembles with Kv alpha-subunits, the N-terminal inactivating domains of Kv beta 1.1 and Kv beta 3 were spliced to the N-terminus of Kv beta 2. The chimaeric beta-subunits (beta 1/ beta 2 and beta 3/ beta 2) induced fast inactivation of several Kv1 channels, indicating that Kv beta 2 associates with these alpha-subunits. No inactivation was induced in Kv 1.3, Kv 1.6, Kv2.1 and Kv3.4 delta 2-28 channels. 5. Kv beta 2 caused a voltage shift in the activation threshold of Kv1.5 of about -10 mV, indicating a putative physiological role. Kv beta 2 had a smaller effect on Kv 1.1 channels. 6. Kv beta 2 accelerated the activation time course of Kv1.5 but had no marked effect on channel deactivation. PMID:8799886

  2. Functional characterization of Kv channel beta-subunits from rat brain.

    PubMed

    Heinemann, S H; Rettig, J; Graack, H R; Pongs, O

    1996-06-15

    1. The potassium channel beta-subunit from rat brain, Kv beta 1.1, is known to induce inactivation of the delayed rectifier channel Kv1.1 and Kv1.4 delta 1-110. 2. Kv beta 1.1 was co-expressed in Xenopus oocytes with various other potassium channel alpha-subunits. Kv beta 1.1 induced inactivation in members of the Kv1 subfamily with the exception of Kv 1.6; no inactivation of Kv 2.1, Kv 3.4 delta 2-28 and Kv4.1 channels could be observed. 3. The second member of the beta-subunit subfamily, Kv beta 2, had a shorter N-terminal end, accelerated inactivation of the A-type channel Kv 1.4, but did not induce inactivation when co-expressed with delayed rectifiers of the Kv1 channel family. 4. To test whether this subunit co-assembles with Kv alpha-subunits, the N-terminal inactivating domains of Kv beta 1.1 and Kv beta 3 were spliced to the N-terminus of Kv beta 2. The chimaeric beta-subunits (beta 1/ beta 2 and beta 3/ beta 2) induced fast inactivation of several Kv1 channels, indicating that Kv beta 2 associates with these alpha-subunits. No inactivation was induced in Kv 1.3, Kv 1.6, Kv2.1 and Kv3.4 delta 2-28 channels. 5. Kv beta 2 caused a voltage shift in the activation threshold of Kv1.5 of about -10 mV, indicating a putative physiological role. Kv beta 2 had a smaller effect on Kv 1.1 channels. 6. Kv beta 2 accelerated the activation time course of Kv1.5 but had no marked effect on channel deactivation.

  3. Path-sensitive analysis for reducing rollback overheads

    DOEpatents

    O'Brien, John K.P.; Wang, Kai-Ting Amy; Yamashita, Mark; Zhuang, Xiaotong

    2014-07-22

    A mechanism is provided for path-sensitive analysis for reducing rollback overheads. The mechanism receives, in a compiler, program code to be compiled to form compiled code. The mechanism divides the code into basic blocks. The mechanism then determines a restore register set for each of the one or more basic blocks to form one or more restore register sets. The mechanism then stores the one or more register sets such that responsive to a rollback during execution of the compiled code. A rollback routine identifies a restore register set from the one or more restore register sets and restores registers identified in the identified restore register set.

  4. SHOULDER MUSCLE IMBALANCE AND SUBACROMIAL IMPINGEMENT SYNDROME IN OVERHEAD ATHLETES

    PubMed Central

    2011-01-01

    Subacromial impingement is a frequent and painful condition among athletes, particularly those involved in overhead sports such as baseball and swimming. There are generally two types of subacromial impingement: structural and functional. While structural impingement is caused by a physical loss of area in the subacromial space due to bony growth or inflammation, functional impingement is a relative loss of subacromial space secondary to altered scapulohumeral mechanics resulting from glenohumeral instability and muscle imbalance. The purpose of this review is to describe the role of muscle imbalance in subacromial impingement in order to guide sports physical therapy evaluation and interventions. PMID:21655457

  5. Improved Overhead Accounting in the NLC Main Linac

    SciTech Connect

    Tenenbaum, P.

    2004-06-10

    The NLC main linac contains 1,116 RF power units, of which 5% are considered ''spares'' for replacement of failed power units, make-up of the energy gain during an RF breakdown, and energy feedback. A more careful accounting for the effects of beam loading indicates that the NLC can operate with less BNS overhead and a smaller mean phase offset than was originally specified, and that as a consequence the total number of spares is actually about 7.9% of the total.

  6. Open channel block of A-type, kv4.3, and delayed rectifier K+ channels, Kv1.3 and Kv3.1, by sibutramine.

    PubMed

    Kim, Sung Eun; Ahn, Hye Sook; Choi, Bok Hee; Jang, Hyun-Jong; Kim, Myung-Jun; Rhie, Duck-Joo; Yoon, Shin-Hee; Jo, Yang-Hyeok; Kim, Myung-Suk; Sung, Ki-Wug; Hahn, Sang June

    2007-05-01

    The effects of sibutramine on voltage-gated K+ channel (Kv)4.3, Kv1.3, and Kv3.1, stably expressed in Chinese hamster ovary cells, were investigated using the whole-cell patch-clamp technique. Sibutramine did not significantly decrease the peak Kv4.3 currents, but it accelerated the rate of decay of current inactivation in a concentration-dependent manner. This phenomenon was effectively characterized by integrating the total current over the duration of a depolarizing pulse to +40 mV. The IC50 value for the sibutramine block of Kv4.3 was 17.3 microM. Under control conditions, the inactivation of Kv4.3 currents could be fit to a biexponential function, and the time constants for the fast and slow components were significantly decreased after the application of sibutramine. The association (k+1) and dissociation (k-1) rate constants for the sibutramine block of Kv 4.3 were 1.51 microM-1s-1 and 27.35 s-1, respectively. The theoretical KD value, derived from k-1/k+1, yielded a value of 18.11 microM. The block of Kv4.3 by sibutramine displayed a weak voltage dependence, increasing at more positive potentials, and it was use-dependent at 2 Hz. Sibutramine did not affect the time course for the deactivating tail currents. Neither steady-state activation and inactivation nor the recovery from inactivation was affected by sibutramine. Sibutramine caused the concentration-dependent block of the Kv1.3 and Kv3.1 currents with an IC50 value of 3.7 and 32.7 microM, respectively. In addition, sibutramine reduced the tail current amplitude and slowed the deactivation of the tail currents of Kv1.3 and Kv3.1, resulting in a crossover phenomenon. These results indicate that sibutramine acts on Kv4.3, Kv1.3, and Kv3.1 as an open channel blocker.

  7. Inhibition of Kv4.3 potassium channels by trazodone.

    PubMed

    Chae, Yun Ju; Choi, Jin-Sung; Hahn, Sang June

    2013-08-01

    Trazodone, a triazolopyridine antidepressant, is commonly used in the treatment of depression and insomnia. Kv4.3 channels are transiently, and rapidly, inactivating Kv channels that are highly expressed in cardiac myocytes and neurons. To determine the electrophysiological basis for the cardiac and neuronal actions of trazodone, we studied the effects of trazodone on Kv4.3 currents stably expressed in Chinese hamster ovary cells using the whole-cell patch-clamp technique. Trazodone decreased the peak amplitude of Kv4.3 in a concentration-dependent manner with an IC50 of 55.4 μM. Under control conditions, the time course of inactivation of Kv4.3 at +40 mV was fitted to a double exponential function. Trazodone produced a concentration-dependent slowing of the fast and slow components of Kv4.3 inactivation during a voltage step to +40 mV. The inhibition of Kv4.3 by trazodone was voltage independent over the entire voltage range tested. Trazodone shifted the voltage dependence of the steady-state inactivation of Kv4.3 to a hyperpolarizing direction. However, the slope factor of the steady-state inactivation was not affected by trazodone. Under control conditions, the closed-state inactivation of Kv4.3 was fitted to a single exponential function. Trazodone significantly accelerated the closed-state inactivation of Kv4.3. Trazodone produced a weak use-dependent inhibition of Kv4.3 at frequencies of 1 and 2 Hz. m-Chlorophenylpiperazine (m-CPP), a major metabolite of trazodone, inhibited Kv4.3 less potently than trazodone, with an IC50 of 118.6 μM. These results suggest that trazodone preferentially inhibited Kv4.3 by both binding to the closed state and accelerating the closed-state inactivation of the channel.

  8. TAUOVERSUPERMON: LOW-OVERHEAD ONLINE PARALLEL PERFORMANCE MONITORING

    SciTech Connect

    SOTTILE, MATTHEW JOSEPH; NATARAJ, AROON; MALONY, ALLEN; MORRIS, ALAN; SHENDE, SAMEER

    2007-01-30

    Online or Real-time application performance monitoring allows tracking performance characteristics during execution as opposed to doing so post-mortem. This opens up several possibilities otherwise unavailable such as real-time visualization and application performance steering that can be useful in the context of long-running applications. Two fundamental components that constitute such a performance monitor are the measurement and transport systems. The former captures performance metrics of individual contexts (processes, threads). The latter enables querying the parallel/distributed state from the different contexts and also allows measurement control. As HPC systems grow in size and complexity, the key challenge is to keep the online performance monitor scalable and low overhead while still providing a useful performance reporting capability. We adapt and combine two existing, mature systems - Tuning and Analysis Utility (TAU) and Supermon - to address this problem. Tau performs the measurement while Supermon is used to collect the distributed measurement state. Our experiments show that this novel approach of using a cluster-monitor, Supermon, as the transport for online performance data from Tau leads to very low-overhead application monitoring as well as other beneits unavailable from using a traditional transport such as NFS.

  9. Vertical Jump Biomechanics Altered With Virtual Overhead Goal.

    PubMed

    Ford, Kevin R; Nguyen, Anh-Dung; Hegedus, Eric J; Taylor, Jeffrey B

    2017-04-01

    Virtual environments with real-time feedback can simulate extrinsic goals that mimic real life conditions. The purpose was to compare jump performance and biomechanics with a physical overhead goal (POG) and with a virtual overhead goal (VOG). Fourteen female subjects participated (age: 18.8 ± 1.1 years, height: 163.2 ± 8.1 cm, weight 63.0 ± 7.9 kg). Sagittal plane trunk, hip, and knee biomechanics were calculated during the landing and take-off phases of drop vertical jump with different goal conditions. Repeated-measures ANOVAs determined differences between goal conditions. Vertical jump height displacement was not different during VOG compared with POG. Greater hip extensor moment (P < .001*) and hip angular impulse (P < .004*) were found during VOG compared with POG. Subjects landed more erect with less magnitude of trunk flexion (P = .002*) during POG compared with VOG. A virtual target can optimize jump height and promote increased hip moments and trunk flexion. This may be a useful alternative to physical targets to improve performance during certain biomechanical testing, screening, and training conditions.

  10. Steal Tree: Low-Overhead Tracing of Work Stealing Schedulers

    SciTech Connect

    Lifflander, Jonathan; Krishnamoorthy, Sriram; Kale, Laxmikant

    2013-06-16

    Work stealing is a popular approach to scheduling task-parallel programs. The flexibility inherent in work stealing when dealing with load imbalance results in seemingly irregular computation structures, complicating the study of its runtime behavior. In this paper, we present an approach to efficiently trace async-finish parallel programs scheduled using work stealing. We identify key properties that allow us to trace the execution of tasks with low time and space overheads. We also study the usefulness of the proposed schemes in supporting algorithms for data-race detection and retentive steal- ing presented in the literature. We demonstrate that the perturbation due to tracing is within the variation in the execution time with 99% confidence and the traces are concise, amounting to a few tens of kilobytes per thread in most cases. We also demonstrate that the traces enable significant reductions in the cost of detecting data races and result in low, stable space overheads in supporting retentive stealing for async-finish programs.

  11. Overhead cam shaft type V-engine cylinder block

    SciTech Connect

    Tominaga, N.; Kurai, N.; Ueno, H.; Suzuki, S.

    1987-01-06

    This patent describes an overhead camshaft type V-engine having V-shaped cylinders equipped with and overhead camshaft drive by a timing chain disposed and arranged on either side of the cylinders at a right angle to a crankshaft. The improvement comprises: a cylinder block; a timing chain passage in the cylinder block, the passage housing the timing chain movement in a plane of the chain. The passage includes a spacing on each side of a pair of runs of the chain, and in the plane, the spacing on each side of a pair of runs of the chain being substantially the same; the block further including a wall at least partially bounding the spacings and intersecting the plane. The wall has symmetrical wall openings therethrough symmetrically disposed on opposite sides of the chain and its plane, and opening into a respective substantially same spacing; a plurality of chain guide means, each mounted in a respective substantially same spacing; and tensioning means resiliently biasing one of the chain guide means toward and against a run of the chain to place the chain in tension, at least a portion of the tensioning means being mounted in one of the symmetrical wall openings adjacent to the respective run. The symmetry of the symmetrical wall openings enable the tensioning means to be positioned adjacent to either run, whereby the cylinder block may be used for diametrically opposite cylinders.

  12. Rehabilitation of the Overhead Athlete’s Elbow

    PubMed Central

    Wilk, Kevin E.; Macrina, Leonard C.; Cain, E. Lyle; Dugas, Jeffrey R.; Andrews, James R.

    2012-01-01

    The activities required during overhead sports, particularly during baseball pitching, produce large forces at the elbow joint. Injuries to the elbow joint frequently occur in the overhead athlete because of the large amount of forces observed during the act of throwing, playing tennis, or playing golf. Injuries may result because of repetitive overuse, leading to tissue failure. Rehabilitation following injury or surgery to the throwing elbow is vital to fully restore normal function and return the athlete to competition as quickly and safely as possible. Rehabilitation of the elbow, whether following injury or postsurgical, must follow a progressive and sequential order, building on the previous phase, to ensure that healing tissues are not compromised. Emphasis is placed on restoring full motion, muscular strength, and neuromuscular control while gradually applying loads to healing tissue. In addition, when one is creating a rehabilitation plan for athletes, it is imperative to treat the entire upper extremity, core, and legs to create and dissipate the forces generated at each joint. PMID:23016113

  13. Modulation of Closed-State Inactivation in Kv2.1/Kv6.4 Heterotetramers as Mechanism for 4-AP Induced Potentiation.

    PubMed

    Stas, Jeroen I; Bocksteins, Elke; Labro, Alain J; Snyders, Dirk J

    2015-01-01

    The voltage-gated K+ (Kv) channel subunits Kv2.1 and Kv2.2 are expressed in almost every tissue. The diversity of Kv2 current is increased by interacting with the electrically silent Kv (KvS) subunits Kv5-Kv6 and Kv8-Kv9, into functional heterotetrameric Kv2/KvS channels. These Kv2/KvS channels possess unique biophysical properties and display a more tissue-specific expression pattern, making them more desirable pharmacological and therapeutic targets. However, little is known about the pharmacological properties of these heterotetrameric complexes. We demonstrate that Kv5.1, Kv8.1 and Kv9.3 currents were inhibited differently by the channel blocker 4-aminopyridine (4-AP) compared to Kv2.1 homotetramers. In contrast, Kv6.4 currents were potentiated by 4-AP while displaying moderately increased affinities for the channel pore blockers quinidine and flecainide. We found that the 4-AP induced potentiation of Kv6.4 currents was caused by modulation of the Kv6.4-mediated closed-state inactivation: suppression by 4-AP of the Kv2.1/Kv6.4 closed-state inactivation recovered a population of Kv2.1/Kv6.4 channels that was inactivated at resting conditions, i.e. at a holding potential of -80 mV. This modulation also resulted in a slower initiation and faster recovery from closed-state inactivation. Using chimeric substitutions between Kv6.4 and Kv9.3 subunits, we demonstrated that the lower half of the S6 domain (S6c) plays a crucial role in the 4-AP induced potentiation. These results demonstrate that KvS subunits modify the pharmacological response of Kv2 subunits when assembled in heterotetramers and illustrate the potential of KvS subunits to provide unique pharmacological properties to the heterotetramers, as is the case for 4-AP on Kv2.1/Kv6.4 channels.

  14. Evaluation of Instrumentation and Dynamic Thermal Ratings for Overhead Lines

    SciTech Connect

    Phillips, A.

    2013-01-31

    In 2010, a project was initiated through a partnership between the Department of Energy (DOE) and the New York Power Authority (NYPA) to evaluate EPRI's rating technology and instrumentation that can be used to monitor the thermal states of transmission lines and provide the required real-time data for real-time rating calculations. The project included the installation and maintenance of various instruments at three 230 kV line sites in northern New York. The instruments were monitored, and data collection and rating calculations were performed for about a three year period.

  15. Development of sensorless easy-to-use overhead crane system via simulation based control

    NASA Astrophysics Data System (ADS)

    Tagawa, Yasutaka; Mori, Yoshihito; Wada, Masaomi; Kawajiri, Eisaku; Nouzuka, Kazuma

    2016-09-01

    This paper describes the newly developed overhead crane which has a sensorless vibration control system. Generally, loads which are carried by the overhead cranes are easy to vibrate and only skilled people can operate the cranes. Therefore, a lot of studies have been done to solve this problem by using feedback control with vibration sensors. However vibration sensors often break down in severe industrial environment and more reliable control systems are required. For this reason, we have been developing sensorless control system for overhead cranes. In this paper, we firstly introduce basic idea of simulation based control which is called IDCS, then overview and modeling of the overhead crane is presented. Next, the control system design of the overhead crane is discussed, and experimental results are shown for real overhead crane with 2 axes.

  16. Visual experience regulates Kv3.1b and Kv3.2 expression in developing rat visual cortex.

    PubMed

    Grabert, J; Wahle, P

    2009-01-23

    Among the GABAergic neocortical interneurons, parvalbumin-containing fast-spiking (FS) basket cells are essential mediators of feed-forward inhibition, network synchrony and oscillations, and timing of the critical period for sensory plasticity. The FS phenotype matures after birth. It depends on the expression of the voltage-gated potassium channels Kv3.1b/3.2 which mediate the fast membrane repolarization necessary for firing fast action potentials at high frequencies. We have now tested in rat visual cortex if visual deprivation affects the Kv3 expression. During normal development, Kv3.1b/3.2 mRNA and protein expression increased in rat visual cortex reaching adult levels around P20. Dark rearing from birth neither prevented nor delayed the upregulation. Rather unexpectedly, the expression of Kv3.1b protein and Kv3.2 mRNA and protein increased to higher levels from the third postnatal week onwards. Triple-labeling revealed that in dark-reared visual cortex Kv3.2 was upregulated in parvalbuminergic interneurons in supragranular layers which in normal animals rarely display Kv3.2 expression. Recovery from dark rearing normalized Kv3.2 expression. This showed that visual experience influences the Kv3 expression. The results suggest that an altered expression of Kv3 channels affects the functional properties of FS neurons, and may contribute to the deficits in inhibition observed in the sensory-deprived cortex.

  17. Effect of tyrphostin AG879 on Kv4.2 and Kv4.3 potassium channels

    PubMed Central

    Yu, Haibo; Zou, Beiyan; Wang, Xiaoliang; Li, Min

    2015-01-01

    Background and Purpose A-type potassium channels (IA) are important proteins for modulating neuronal membrane excitability. The expression and activity of Kv4.2 channels are critical for neurological functions and pharmacological inhibitors of Kv4.2 channels may have therapeutic potential for Fragile X syndrome. While screening various compounds, we identified tyrphostin AG879, a tyrosine kinase inhibitor, as a Kv4.2 inhibitor from. In the present study we characterized the effect of AG879 on cloned Kv4.2/Kv channel-interacting protein 2 (KChIP2) channels. Experimental Approach To screen the library of pharmacologically active compounds, the thallium flux assay was performed on HEK-293 cells transiently-transfected with Kv4.2 cDNA using the Maxcyte transfection system. The effects of AG879 were further examined on CHO-K1 cells expressing Kv4.2/KChIP2 channels using a whole-cell patch-clamp technique. Key Results Tyrphostin AG879 selectively and dose-dependently inhibited Kv4.2 and Kv4.3 channels. In Kv4.2/KChIP2 channels, AG879 induced prominent acceleration of the inactivation rate, use-dependent block and slowed the recovery from inactivation. AG879 induced a hyperpolarizing shift in the voltage-dependence of the steady-state inactivation of Kv4.2 channels without apparent effect on the V1/2 of the voltage-dependent activation. The blocking effect of AG879 was enhanced as channel inactivation increased. Furthermore, AG879 significantly inhibited the A-type potassium currents in the cultured hippocampus neurons. Conclusion and Implications AG879 was identified as a selective and potent inhibitor the Kv4.2 channel. AG879 inhibited Kv4.2 channels by preferentially interacting with the open state and further accelerating their inactivation. PMID:25752739

  18. Kv7 Channels Can Function without Constitutive Calmodulin Tethering

    PubMed Central

    Alberdi, Araitz; Alaimo, Alessandro; Etxeberría, Ainhoa; Fernández-Orth, Juncal; Zamalloa, Teresa; Roura-Ferrer, Meritxell; Villace, Patricia; Areso, Pilar; Casis, Oscar; Villarroel, Alvaro

    2011-01-01

    M-channels are voltage-gated potassium channels composed of Kv7.2-7.5 subunits that serve as important regulators of neuronal excitability. Calmodulin binding is required for Kv7 channel function and mutations in Kv7.2 that disrupt calmodulin binding cause Benign Familial Neonatal Convulsions (BFNC), a dominantly inherited human epilepsy. On the basis that Kv7.2 mutants deficient in calmodulin binding are not functional, calmodulin has been defined as an auxiliary subunit of Kv7 channels. However, we have identified a presumably phosphomimetic mutation S511D that permits calmodulin-independent function. Thus, our data reveal that constitutive tethering of calmodulin is not required for Kv7 channel function. PMID:21980481

  19. Quantitative analysis of neurons with Kv3 potassium channel subunits, Kv3.1b and Kv3.2, in macaque primary visual cortex.

    PubMed

    Constantinople, Christine M; Disney, Anita A; Maffie, Jonathan; Rudy, Bernardo; Hawken, Michael J

    2009-10-01

    Voltage-gated potassium channels that are composed of Kv3 subunits exhibit distinct electrophysiological properties: activation at more depolarized potentials than other voltage-gated K+ channels and fast kinetics. These channels have been shown to contribute to the high-frequency firing of fast-spiking (FS) GABAergic interneurons in the rat and mouse brain. In the rodent neocortex there are distinct patterns of expression for the Kv3.1b and Kv3.2 channel subunits and of coexpression of these subunits with neurochemical markers, such as the calcium-binding proteins parvalbumin (PV) and calbindin D-28K (CB). The distribution of Kv3 channels and interrelationship with calcium-binding protein expression has not been investigated in primate cortex. We used immunoperoxidase and immunofluorescent labeling and stereological counting techniques to characterize the laminar and cell-type distributions of Kv3-immunoreactive (ir) neurons in macaque V1. We found that across the cortical layers approximately 25% of both Kv3.1b- and Kv3.2-ir neurons are non-GABAergic. In contrast, all Kv3-ir neurons in rodent cortex are GABAergic (Chow et al. [1999] J Neurosci. 19:9332-9345). The putatively excitatory Kv3-ir neurons were mostly located in layers 2, 3, and 4b. Further, the proportion of Kv3-ir neurons that express PV or CB also differs between macaque V1 and rodent cortex. These data indicate that, within the population of cortical neurons, a broader population of neurons, encompassing cells of a wider range of morphological classes may be capable of sustaining high-frequency firing in macaque V1.

  20. Development of extruded dielectric underground transmission cables rated 138 kV, 230 kV, and 345 kV. Final report

    SciTech Connect

    Bahder, G.; Bopp, L.A.; Eager, G.S.; Katz, C.; Knott, A.; Schmidt, G.A.

    1982-02-01

    This report covers the continuation of the work to develop technology to manufacture chemically crosslinked polyethylene insulated power cables in the ac voltage range of 138 kV to 345 kV having insulation thicknesses approximately equal to that of oil impregnated paper insulated cables. It also incorporates the development of field molded splices and terminations for new high voltage stress 138 kV cables. After reviewing the main equipment elements, incorporated in the pilot extrusion line, the special features of this system are noted and a step-by-step description of the cable extrusion process is given. Optimization of the process and introduction of modifications in the equipment culminated with the production of 138 kV cables. Results of laboratory tests to demonstrate the high quality of the cables are given. The development of molded splices and molded stress control cones was initiated with the work on model cables and followed by the making of splices and terminations on 138 kV cables. The molded components are made with the same purified insulating compound as used in the manufacture of the cables. Both the molded splices and the molded stress control cones have been fully tested in the laboratory. Following the completion of the development of the 138 kV cable a high stress 230 kV crosslinked polyethylene cable was developed and optimized. A full evaluation program similar to the one utilized on the 138 kV cable was carried out. Subsequently, work to develop a 345 kV high voltage stress cable, having insulation thickness of 1.02'' was undertaken. 345 kV cables were successfully manufactured and tested. However, additional work is required to further optimize the quality of this cable.

  1. Implementation of a novel double-side technique for partial discharge detection and location in covered conductor overhead distribution networks

    NASA Astrophysics Data System (ADS)

    He, Weisheng; Li, Hongjie; Liang, Deliang; Sun, Haojie; Yang, Chenbo; Wei, Jinqu; Yuan, Zhijian

    2015-12-01

    Partial discharge (PD) detection has proven to be one of the most acceptable techniques for on-line condition monitoring and predictive maintenance of power apparatus. A powerful tool for detecting PD in covered-conductor (CC) lines is urgently needed to improve the asset management of CC overhead distribution lines. In this paper, an appropriate, portable and simple system designed to detect PD activity in CC lines and ultimately pinpoint the PD source is developed and tested. The system is based on a novel double-side synchronised PD measurement technique driven by pulse injection. Emphasis is placed on the proposed PD-location mechanism and hardware structure, with descriptions of the pulse-injection process, detection device, synchronisation principle and PD-location algorithm. The system is simulated using ATP-EMTP, and the simulated results are found to be consistent with the actual simulation layout. For further validation, the capability of the system is tested in a high-voltage laboratory experiment using a 10-kV CC line with cross-linked polyethylene insulation.

  2. Software in the DOE: The Hidden Overhead of''The Build''

    SciTech Connect

    Kumfert, G; Epperly, T

    2002-02-28

    ''The Build'' is the infrastructure needed to convert software from source code to usable form. It is intimately tied to the software it supports, knowing about every file and automating every transformation needed to produce a working program. Every developer knows that a project spends some labor overhead on ''the build.'' How big is this hidden overhead? According to 34 scientific software developers we surveyed at Lawrence Livermore National Labs, among colleagues at other DOE labs, and a handful of academics the ''perceived'' overhead averages around 12%. Individual cases of 20% to 30% were not uncommon. In one project claiming a 20% overhead, we found supporting evidence by combing through their CVS repository.

  3. Contributions of Kv3 channels to neuronal excitability.

    PubMed

    Rudy, B; Chow, A; Lau, D; Amarillo, Y; Ozaita, A; Saganich, M; Moreno, H; Nadal, M S; Hernandez-Pineda, R; Hernandez-Cruz, A; Erisir, A; Leonard, C; Vega-Saenz de Miera, E

    1999-04-30

    Four mammalian Kv3 genes have been identified, each of which generates, by alternative splicing, multiple protein products differing in their C-terminal sequence. Products of the Kv3.1 and Kv3.2 genes express similar delayed-rectifier type currents in heterologous expression systems, while Kv3.3 and Kv3.4 proteins express A-type currents. All Kv3 currents activate relatively fast at voltages more positive than -10 mV, and deactivate very fast. The distribution of Kv3 mRNAs in the rodent CNS was studied by in situ hybridization, and the localization of Kv3.1 and Kv3.2 proteins has been studied by immunohistochemistry. Most Kv3.2 mRNAs (approximately 90%) are present in thalamic-relay neurons throughout the dorsal thalamus. The protein is expressed mainly in the axons and terminals of these neurons. Kv3.2 channels are thought to be important for thalamocortical signal transmission. Kv3.1 and Kv3.2 proteins are coexpressed in some neuronal populations such as in fast-spiking interneurons of the cortex and hippocampus, and neurons in the globus pallidus. Coprecipitation studies suggest that in these cells the two types of protein form heteromeric channels. Kv3 proteins appear to mediate, in native neurons, similar currents to those seen in heterologous expression systems. The activation voltage and fast deactivation rates are believed to allow these channels to help repolarize action potentials fast without affecting the threshold for action potential generation. The fast deactivating current generates a quickly recovering after hyperpolarization, thus maximizing the rate of recovery of Na+ channel inactivation without contributing to an increase in the duration of the refractory period. These properties are believed to contribute to the ability of neurons to fire at high frequencies and to help regulate the fidelity of synaptic transmission. Experimental evidence has now become available showing that Kv3.1-Kv3.2 channels play critical roles in the generation of fast

  4. The anticonvulsant retigabine suppresses neuronal KV2-mediated currents

    PubMed Central

    Stas, Jeroen I.; Bocksteins, Elke; Jensen, Camilla S.; Schmitt, Nicole; Snyders, Dirk J.

    2016-01-01

    Enhancement of neuronal M-currents, generated through KV7.2-KV7.5 channels, has gained much interest for its potential in developing treatments for hyperexcitability-related disorders such as epilepsy. Retigabine, a KV7 channel opener, has proven to be an effective anticonvulsant and has recently also gained attention due to its neuroprotective properties. In the present study, we found that the auxiliary KCNE2 subunit reduced the KV7.2-KV7.3 retigabine sensitivity approximately 5-fold. In addition, using both mammalian expression systems and cultured hippocampal neurons we determined that low μM retigabine concentrations had ‘off-target’ effects on KV2.1 channels which have recently been implicated in apoptosis. Clinical retigabine concentrations (0.3–3 μM) inhibited KV2.1 channel function upon prolonged exposure. The suppression of the KV2.1 conductance was only partially reversible. Our results identified KV2.1 as a new molecular target for retigabine, thus giving a potential explanation for retigabine’s neuroprotective properties. PMID:27734968

  5. Reducing the quantum-computing overhead with complex gate distillation

    NASA Astrophysics Data System (ADS)

    Duclos-Cianci, Guillaume; Poulin, David

    2015-04-01

    In leading fault-tolerant quantum-computing schemes, accurate transformations are obtained by a two-stage process. In a first stage, a discrete universal set of fault-tolerant operations is obtained by error-correcting noisy transformations and distilling resource states. In a second stage, arbitrary transformations are synthesized to desired accuracy by combining elements of this set into a circuit. Here we present a scheme that merges these two stages into a single one, directly distilling complex transformations. We find that our scheme can reduce the total overhead to realize certain gates by up to a few orders of magnitude. In contrast to other schemes, this efficient gate synthesis does not require computationally intensive compilation algorithms and a straightforward generalization of our scheme circumvents compilation and synthesis altogether.

  6. Wearable IMU for Shoulder Injury Prevention in Overhead Sports.

    PubMed

    Rawashdeh, Samir A; Rafeldt, Derek A; Uhl, Timothy L

    2016-11-03

    Body-worn inertial sensors have enabled motion capture outside of the laboratory setting. In this work, an inertial measurement unit was attached to the upper arm to track and discriminate between shoulder motion gestures in order to help prevent shoulder over-use injuries in athletics through real-time preventative feedback. We present a detection and classification approach that can be used to count the number of times certain motion gestures occur. The application presented involves tracking baseball throws and volleyball serves, which are common overhead movements that can lead to shoulder and elbow overuse injuries. Eleven subjects are recruited to collect training, testing, and randomized validation data, which include throws, serves, and seven other exercises that serve as a large null class of similar movements, which is analogous to a realistic usage scenario and requires a robust estimator.

  7. Wearable IMU for Shoulder Injury Prevention in Overhead Sports

    PubMed Central

    Rawashdeh, Samir A.; Rafeldt, Derek A.; Uhl, Timothy L.

    2016-01-01

    Body-worn inertial sensors have enabled motion capture outside of the laboratory setting. In this work, an inertial measurement unit was attached to the upper arm to track and discriminate between shoulder motion gestures in order to help prevent shoulder over-use injuries in athletics through real-time preventative feedback. We present a detection and classification approach that can be used to count the number of times certain motion gestures occur. The application presented involves tracking baseball throws and volleyball serves, which are common overhead movements that can lead to shoulder and elbow overuse injuries. Eleven subjects are recruited to collect training, testing, and randomized validation data, which include throws, serves, and seven other exercises that serve as a large null class of similar movements, which is analogous to a realistic usage scenario and requires a robust estimator. PMID:27827880

  8. Hydro-mechanical overhead for internal combustion engine

    SciTech Connect

    Meistrick, Z.S.; Price, R.B.

    1987-05-12

    This patent describes a hydro-mechanical overhead for a multi-cylinder four-cycle internal combustion engine having a camshaft, intake valve pushtube means driven by the camshaft, exhaust valve pushtube means driven by the camshaft, at least one intake and exhaust valve for each cylinder of the multi-cylinder internal combustion engines and a piston for each cylinder of the engine. The process comprises an intake valve master piston means for each engine cylinder. Each intake valve master piston means is driven by one of the intake valve pushtube means. There is an exhaust valve master piston means for each engine cylinder, and each exhaust valve master piston means is driven by one of the exhaust valve pushtube means.

  9. Phase Sensitive Cueing for 3D Objects in Overhead Images

    SciTech Connect

    Paglieroni, D W; Eppler, W G; Poland, D N

    2005-02-18

    A 3D solid model-aided object cueing method that matches phase angles of directional derivative vectors at image pixels to phase angles of vectors normal to projected model edges is described. It is intended for finding specific types of objects at arbitrary position and orientation in overhead images, independent of spatial resolution, obliqueness, acquisition conditions, and type of imaging sensor. It is shown that the phase similarity measure can be efficiently evaluated over all combinations of model position and orientation using the FFT. The highest degree of similarity over all model orientations is captured in a match surface of similarity values vs. model position. Unambiguous peaks in this surface are sorted in descending order of similarity value, and the small image thumbnails that contain them are presented to human analysts for inspection in sorted order.

  10. Combined MV + kV inverse treatment planning for optimal kV dose incorporation in IGRT

    NASA Astrophysics Data System (ADS)

    Grelewicz, Zachary; Wiersma, Rodney D.

    2014-04-01

    Despite the existence of real-time kV intra-fractional tumor tracking strategies for many years, clinical adoption has been held back by concern over the excess kV imaging dose cost to the patient when imaging in continuous fluoroscopic mode. This work aims to solve this problem by investigating, for the first time, the use of convex optimization tools to optimally integrate this excess kV imaging dose into the MV therapeutic dose in order to make real-time kV tracking clinically feasible. Phase space files modeling both a 6 MV treatment beam and a kV on-board-imaging beam of a commercial LINAC were generated with BEAMnrc, and used to generate dose influence matrices in DOSXYZnrc for ten previously treated lung cancer patients. The dose optimization problem for IMRT, formulated as a quadratic problem, was modified to include additional constraints as required for real-time kV intra-fractional tracking. An interior point optimizer was used to solve the modified optimization problem. It was found that when using large kV imaging apertures during fluoroscopic tracking, combined MV + kV optimization lead to a 0.5%-5.17% reduction in the total number of monitor units assigned to the MV beam due to inclusion of the kV dose over the ten patients. This was accompanied by a reduction of up to 42% of the excess kV dose compared to standard MV IMRT with kV tracking. For all kV field sizes considered, combined MV + kV optimization provided prescription dose to the treatment volume coverage equal to the no-imaging case, yet superior to standard MV IMRT with non-optimized kV fluoroscopic tracking. With combined MV + kV optimization, it is possible to quantify in a patient specific way the dosimetric effect of real-time imaging on the patient. Such information is necessary when substantial kV imaging is performed.

  11. Constitutive Activation of the Shaker Kv Channel

    PubMed Central

    Sukhareva, Manana; Hackos, David H.; Swartz, Kenton J.

    2003-01-01

    In different types of K+ channels the primary activation gate is thought to reside near the intracellular entrance to the ion conduction pore. In the Shaker Kv channel the gate is closed at negative membrane voltages, but can be opened with membrane depolarization. In a previous study of the S6 activation gate in Shaker (Hackos, D.H., T.H. Chang, and K.J. Swartz. 2002. J. Gen. Physiol. 119:521–532.), we found that mutation of Pro 475 to Asp results in a channel that displays a large macroscopic conductance at negative membrane voltages, with only small increases in conductance with membrane depolarization. In the present study we explore the mechanism underlying this constitutively conducting phenotype using both macroscopic and single-channel recordings, and probes that interact with the voltage sensors or the intracellular entrance to the ion conduction pore. Our results suggest that constitutive conduction results from a dramatic perturbation of the closed-open equilibrium, enabling opening of the activation gate without voltage-sensor activation. This mechanism is discussed in the context of allosteric models for activation of Kv channels and what is known about the structure of this critical region in K+ channels. PMID:14557403

  12. 220-kV combined optical transformer

    NASA Astrophysics Data System (ADS)

    Cui, Ying; Ye, Miaoyuan; Zhu, Yong; Xu, Yan; Luo, Sunan

    2000-10-01

    The magneto-optic current and electro-optic voltage sensing technologies were combined into a single phase unit which provides a new solution for combined current and voltage sensing and relaying applications. It senses voltage and current by making utilities of Pockels electro-optic effect of a BGO(Bi4Ge3O12) crystal and Faraday magneto-optic effect of a close-loop flint. The 220 kV high voltage is directly applied on the BGO crystal without capacitive dividers. This design permits true optical voltage measurement to be performed for the highest possible accuracy and stability. In the current sensor, a light beam circles around the current carrying conductor. The effect of the location movement of the conductor and external magnetic field are reduced. It has superior advantages of compact size, light- weight and better performance compared with conventional current and voltage transformers. Composite bushing consisting of a fiberglass tube support and silicone rubber that is filled with SF6 gas is employed for HV insulation. Connections between the Combined Optical Transformers in the substation and the metering and protecting unit in the control house are via optical fiber cable. The fundamental principal, system design and test result of this new 220 kV Combined Optical Transformer will be introduced in this paper.

  13. Effect of NIP-142 on potassium channel alpha-subunits Kv1.5, Kv4.2 and Kv4.3, and mouse atrial repolarization.

    PubMed

    Tanaka, Hikaru; Namekata, Iyuki; Hamaguchi, Shogo; Kawamura, Taro; Masuda, Hiroyuki; Tanaka, Yoshio; Iida-Tanaka, Naoko; Takahara, Akira

    2010-01-01

    Effects of NIP-142, a benzopyran compound which terminates experimental atrial arrhythmia, on potassium channel alpha-subunits and mouse atrial repolarization were examined. NIP-142 concentration-dependently blocked the outward current through potassium channel alpha subunits Kv1.5, Kv4.2 and Kv4.3 expressed in Xenopus oocytes. In isolated mouse atrial myocardia, NIP-142 prolonged the action potential duration and effective refractory period, and increased the contractile force. These results suggest that NIP-142 blocks the potassium channels underlying the transient and sustained outward currents, which may contribute to its antiarrhythmic activity.

  14. How To Prepare Effective Overhead Projector Presentations: One Picture Is Worth a Thousand Words.

    ERIC Educational Resources Information Center

    National Audio-Visual Supply, East Rutherford, NJ.

    Designed to help create effective presentations, this guide describes the basic techniques and provides hints for producing professional, attention-getting overhead transparencies in a step-by-step procedure format. Eight topics are addressed in the guide: (1) eight steps to a successful meeting presentation; (2) advantages of overhead projection;…

  15. 30 CFR 57.19110 - Overhead protection for shaft deepening work.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Overhead protection for shaft deepening work... NONMETAL MINES Personnel Hoisting Shafts § 57.19110 Overhead protection for shaft deepening work. A substantial bulkhead or equivalent protection shall be provided above persons at work deepening a shaft....

  16. 30 CFR 56.19110 - Overhead protection for shaft deepening work.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Overhead protection for shaft deepening work... MINES Personnel Hoisting Shafts § 56.19110 Overhead protection for shaft deepening work. A substantial bulkhead or equivalent protection shall be provided above persons at work deepening a shaft....

  17. 31 CFR Appendix I(f) to Part 13 - Estimated Overhead and Administrative Costs

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance: Treasury 1 2012-07-01 2012-07-01 false Estimated Overhead and Administrative Costs I(F) Appendix I(F) to Part 13 Money and Finance: Treasury Office of the Secretary of the Treasury... Pt. 13, App. I(F) Appendix I(F) to Part 13—Estimated Overhead and Administrative Costs Date:...

  18. 31 CFR Appendix I(f) to Part 13 - Estimated Overhead and Administrative Costs

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance: Treasury 1 2013-07-01 2013-07-01 false Estimated Overhead and Administrative Costs I(F) Appendix I(F) to Part 13 Money and Finance: Treasury Office of the Secretary of the Treasury... Pt. 13, App. I(F) Appendix I(F) to Part 13—Estimated Overhead and Administrative Costs Date:...

  19. 31 CFR Appendix II(f) to Part 13 - Overhead and Administrative Costs

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Overhead and Administrative Costs II(F) Appendix II(F) to Part 13 Money and Finance: Treasury Office of the Secretary of the Treasury... Pt. 13, App. II(F) Appendix II(F) to Part 13—Overhead and Administrative Costs Date: Select Only...

  20. 31 CFR Appendix II(f) to Part 13 - Overhead and Administrative Costs

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance: Treasury 1 2011-07-01 2011-07-01 false Overhead and Administrative Costs II(F) Appendix II(F) to Part 13 Money and Finance: Treasury Office of the Secretary of the Treasury... Pt. 13, App. II(F) Appendix II(F) to Part 13—Overhead and Administrative Costs Date: Select Only...

  1. 31 CFR Appendix I(f) to Part 13 - Estimated Overhead and Administrative Costs

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance: Treasury 1 2011-07-01 2011-07-01 false Estimated Overhead and Administrative Costs I(F) Appendix I(F) to Part 13 Money and Finance: Treasury Office of the Secretary of the Treasury... Pt. 13, App. I(F) Appendix I(F) to Part 13—Estimated Overhead and Administrative Costs Date:...

  2. 31 CFR Appendix I(f) to Part 13 - Estimated Overhead and Administrative Costs

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Estimated Overhead and Administrative Costs I(F) Appendix I(F) to Part 13 Money and Finance: Treasury Office of the Secretary of the Treasury... Pt. 13, App. I(F) Appendix I(F) to Part 13—Estimated Overhead and Administrative Costs Date:...

  3. Arrangement of Kv1 alpha subunits dictates sensitivity to tetraethylammonium.

    PubMed

    Al-Sabi, Ahmed; Shamotienko, Oleg; Dhochartaigh, Sorcha Ni; Muniyappa, Nagesh; Le Berre, Marie; Shaban, Hamdy; Wang, Jiafu; Sack, Jon T; Dolly, J Oliver

    2010-09-01

    Shaker-related Kv1 channels contain four channel-forming alpha subunits. Subfamily member Kv1.1 often occurs oligomerized with Kv1.2 alpha subunits in synaptic membranes, and so information was sought on the influence of their positions within tetramers on the channels' properties. Kv1.1 and 1.2 alpha genes were tandem linked in various arrangements, followed by expression as single-chain proteins in mammalian cells. As some concatenations reported previously seemed not to reliably position Kv1 subunits in their assemblies, the identity of expressed channels was methodically evaluated. Surface protein, isolated by biotinylation of intact transiently transfected HEK-293 cells, gave Kv1.1/1.2 reactivity on immunoblots with electrophoretic mobilities corresponding to full-length concatenated tetramers. There was no evidence of protein degradation, indicating that concatemers were delivered intact to the plasmalemma. Constructs with like genes adjacent (Kv1.1-1.1-1.2-1.2 or Kv1.2-1.2-1.1-1.1) yielded delayed-rectifying, voltage-dependent K(+) currents with activation parameters and inactivation kinetics slightly different from the diagonally positioned genes (Kv1.1-1.2-1.1-1.2 or 1.2-1.1-1.2-1.1). Pore-blocking petidergic toxins, alpha dendrotoxin, agitoxin-1, tityustoxin-Kalpha, and kaliotoxin, were unable to distinguish between the adjacent and diagonal concatamers. Unprecedentedly, external application of the pore-blocker tetraethylammonium (TEA) differentially inhibited the adjacent versus diagonal subunit arrangements, with diagonal constructs having enhanced susceptibility. Concatenation did not directly alter the sensitivities of homomeric Kv1.1 or 1.2 channels to TEA or the toxins. TEA inhibition of currents generated by channels made up from dimers (Kv1.1-1.2 and/or Kv1.2-1.1) was similar to the adjacently arranged constructs. These collective findings indicate that assembly of alpha subunits can be directed by this optimized concatenation, and that subunit

  4. Overhead camshaft engine valve train with slack take up means

    SciTech Connect

    Hayashi, Y.

    1987-03-03

    A valve train of an overhead camshaft engine is described comprising: a valve stem; a valve operating cam; a rocker arm operatively engaged with the valve stem and the cam for transferring motion from the cam to the valve stem and having at a part where it is operatively engaged with the cam a hole; a tappet reciprocatingly mounted in the hole in a manner to define an oil pressure chamber variable in volume in accordance with actual movement of the tappet and having an end protruding from the rocker arm to contact the cam; a source of pressurized oil; passageway means for providing communication between the source of pressurized oil and the oil pressure chamber; check valve means operatively connected with the passageway means for preventing a return flow out of the oil pressure chamber; a spring disposed in the oil pressure chamber to urge the tappet in the direction causing the oil pressure chamber to increase in volume to thereby take up slack in the valve train; and an oil releasing passageway having one end opening directly into the uppermost part of the oil pressure chamber and another end opening to the outside of the rocker arm.

  5. Assessment of 69 kV Underground Cable Thermal Ratings using Distributed Temperature Sensing

    NASA Astrophysics Data System (ADS)

    Stowers, Travis

    Underground transmission cables in power systems are less likely to experience electrical faults, however, resulting outage times are much greater in the event that a failure does occur. Unlike overhead lines, underground cables are not self-healing from flashover events. The faulted section must be located and repaired before the line can be put back into service. Since this will often require excavation of the underground duct bank, the procedure to repair the faulted section is both costly and time consuming. These added complications are the prime motivators for developing accurate and reliable ratings for underground cable circuits. This work will review the methods by which power ratings, or ampacity, for underground cables are determined and then evaluate those ratings by making comparison with measured data taken from an underground 69 kV cable, which is part of the Salt River Project (SRP) power subtransmission system. The process of acquiring, installing, and commissioning the temperature monitoring system is covered in detail as well. The collected data are also used to evaluate typical assumptions made when determining underground cable ratings such as cable hot-spot location and ambient temperatures. Analysis results show that the commonly made assumption that the deepest portion of an underground power cable installation will be the hot-spot location does not always hold true. It is shown that distributed cable temperature measurements can be used to locate the proper line segment to be used for cable ampacity calculations.

  6. Fatigue during prolonged intermittent overhead work: reliability of measures and effects of working height.

    PubMed

    Sood, Deepti; Nussbaum, Maury A; Hager, Kris

    2007-04-01

    Shoulder pain is prevalent among industrial workers and existing evidence supports that overhead work is an important specific risk factor. Existing guidelines are limited, with overhead work typically recommended to be avoided, and research on overhead work has been mixed in terms of the effects of increasing arm reach. A laboratory-based simulation of overhead work was conducted, at three working heights, in order to facilitate improved guidelines and to identify potential non-linear effects of overhead work height. Several indicators of shoulder fatigue served as outcome measures and a preliminary study was performed to assess the reliability of several of these measures. Fatigue measures based on electromyography (EMG) generally had low reliability, whereas excellent reliability was exhibited for ratings of perceived discomfort (RPD). Consistent with this, no effects of overhead work height were found on EMG-based measures, yet clear non-linear effects were found on RPD and task performance. The source of the effects of work height appeared to be related to a combination of muscle activation levels and demands on precision/control at the highest location. These results support the utility of subjective measures for relatively low-level intermittent exertions and demonstrate increasingly detrimental fatigue and performance effects at extremes in reach during overhead work.

  7. 75 FR 44288 - Overhead and Gantry Cranes; Extension of the Office of Management and Budget's (OMB) Approval of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-28

    ... Occupational Safety and Health Administration Overhead and Gantry Cranes; Extension of the Office of Management...) approval of the information collection requirements specified in the Standard on Overhead and Gantry Cranes... is a result of new information showing that there are 31,495 overhead and gantry cranes in use,...

  8. 78 FR 68477 - Overhead and Gantry Cranes; Extension of the Office of Management and Budget's (OMB) Approval of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-14

    ... Occupational Safety and Health Administration Overhead and Gantry Cranes; Extension of the Office of Management...) approval of the information collection requirements specified in the Standard on Overhead and Gantry Cranes... Standard on Overhead and Gantry Cranes specify requirements for: Marking the rated load of cranes;...

  9. 29 CFR 1926.1003 - Overhead protection for operators of agricultural and industrial tractors used in construction.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... REGULATIONS FOR CONSTRUCTION Rollover Protective Structures; Overhead Protection § 1926.1003 Overhead...) Purpose. When overhead protection is provided on wheel-type agricultural and industrial tractors, the... accidental upset. (2) Applicability. This standard applies to wheel-type agricultural and industrial...

  10. 29 CFR 1926.1003 - Overhead protection for operators of agricultural and industrial tractors used in construction.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... REGULATIONS FOR CONSTRUCTION Rollover Protective Structures; Overhead Protection § 1926.1003 Overhead...) Purpose. When overhead protection is provided on wheel-type agricultural and industrial tractors, the... accidental upset. (2) Applicability. This standard applies to wheel-type agricultural and industrial...

  11. 29 CFR 1926.1003 - Overhead protection for operators of agricultural and industrial tractors used in construction.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... REGULATIONS FOR CONSTRUCTION Rollover Protective Structures; Overhead Protection § 1926.1003 Overhead...) Purpose. When overhead protection is provided on wheel-type agricultural and industrial tractors, the... accidental upset. (2) Applicability. This standard applies to wheel-type agricultural and industrial...

  12. 29 CFR 1926.1003 - Overhead protection for operators of agricultural and industrial tractors used in construction.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... REGULATIONS FOR CONSTRUCTION Rollover Protective Structures; Overhead Protection § 1926.1003 Overhead...) Purpose. When overhead protection is provided on wheel-type agricultural and industrial tractors, the... accidental upset. (2) Applicability. This standard applies to wheel-type agricultural and industrial...

  13. Kv3.4 channel function and dysfunction in nociceptors

    PubMed Central

    Ritter, David M; Zemel, Benjamin M; Lepore, Angelo C; Covarrubias, Manuel

    2015-01-01

    Recently, we reported the isolation of the Kv3.4 current in dorsal root ganglion (DRG) neurons and described dysregulation of this current in a spinal cord injury (SCI) model of chronic pain. These studies strongly suggest that rat Kv3.4 channels are major regulators of excitability in DRG neurons from pups and adult females, where they help determine action potential (AP) repolarization and spiking properties. Here, we characterized the Kv3.4 current in rat DRG neurons from adult males and show that it transfers 40–70% of the total repolarizing charge during the AP across all ages and sexes. Following SCI, we also found remodeling of the repolarizing currents during the AP. In the light of these studies, homomeric Kv3.4 channels expressed in DRG nociceptors are emerging novel targets that may help develop new approaches to treat neuropathic pain. PMID:26039360

  14. Kv3.4 channel function and dysfunction in nociceptors.

    PubMed

    Ritter, David M; Zemel, Benjamin M; Lepore, Angelo C; Covarrubias, Manuel

    2015-01-01

    Recently, we reported the isolation of the Kv3.4 current in dorsal root ganglion (DRG) neurons and described dysregulation of this current in a spinal cord injury (SCI) model of chronic pain. These studies strongly suggest that rat Kv3.4 channels are major regulators of excitability in DRG neurons from pups and adult females, where they help determine action potential (AP) repolarization and spiking properties. Here, we characterized the Kv3.4 current in rat DRG neurons from adult males and show that it transfers 40-70% of the total repolarizing charge during the AP across all ages and sexes. Following SCI, we also found remodeling of the repolarizing currents during the AP. In the light of these studies, homomeric Kv3.4 channels expressed in DRG nociceptors are emerging novel targets that may help develop new approaches to treat neuropathic pain.

  15. [The story of K.V. Tjellesen].

    PubMed

    Clemmensen, Peter

    2005-01-01

    This is the story about a Danish pharmaceutical wholesaler. The story begins in 1909 in some basement rooms located in Vester Boulevard 42 (which was later to become the Boulevard of H.C. Andersen) in Copenhagen. The founder of the company, pharmacist Knud Valdemar Tjellesen, lived in the very same building. In the beginning, the company mainly sold chemicals and produced and sold chemical-technical products. In 1930, K.V. Tjellesen became the proprietor of the pharmacy Sct. Johannes Apotek situated in Fredensgade 5, Nørrebro in Copenhagen. The company then moved into some offices that were located just behind the pharmacy. Already in 1918, K.V. Tjellesen traded pharmaceutical specialties, which were imported, to a certain extent, from Germany through a purchasing office in Hamburg. In 1938, the son of Knud Valdemar Tjellesen, pharmacist Paul Tjellesen, joined the wholesale company charged with the primary task of intensifying the sale of the company's international agency products. At the same time, the general partnership K.V. Tjellesen was founded. In the time leading up to the Second World War and during this time, business was of course complicated by currency and import restrictions, and it was very difficult to make deliveries to the pharmacies. In Copenhagen, the articles were delivered by 10-12 bicycle delivery boys. In the beginning, the wholesale company mainly catered for Copenhagen and Zealand, but due to the excellent performance of Paul Tjellesen, more and more customers emerged in the rest of the country. In 1954, the company moved to Niels Ebbesens Vej 29 in Frederiksberg given the need for larger facilities. In 1963, an increased space requirement, once again, forced the company to buy one of the neighbouring buildings on Niels Ebbesens Vej and H.C. Orsteds Vej. For many years after, H.C. Orsteds Vej 22 was the official address of the company. After more than 45 years in the company, Paul Tjellesen agreed with his son-in-law Peter Sch

  16. Steel tanks T5 and T4 with overhead pipeline between. Redwood ...

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

    Steel tanks T5 and T4 with overhead pipeline between. Redwood tanks seen in background - Hawaii Volcanoes National Park Water Collection System, Hawaii Volcanoes National Park, Volcano, Hawaii County, HI

  17. Detail, cyclops 15ton overhead traveling crane and rails running the ...

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

    Detail, cyclops 15-ton overhead traveling crane and rails running the length of the building - Wellton-Mohawk Irrigation System, Pumping Plant No. 1, Bounded by Gila River & Union Pacific Railroad, Wellton, Yuma County, AZ

  18. 15. VIEW OF THE ORIGINAL 10TON OVERHEAD NILES TRAVELING CRANE. ...

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

    15. VIEW OF THE ORIGINAL 10-TON OVERHEAD NILES TRAVELING CRANE. - Washington Water Power Company Post Falls Power Plant, Middle Channel Powerhouse & Dam, West of intersection of Spokane & Fourth Streets, Post Falls, Kootenai County, ID

  19. Detail, 25ton overhead traveling crane built by The Craneveyor Corporation, ...

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

    Detail, 25-ton overhead traveling crane built by The Craneveyor Corporation, Los Angeles, California - Wellton-Mohawk Irrigation System, Pumping Plant No. 3, South of Interstate 8, Wellton, Yuma County, AZ

  20. Allele-dependent changes of olivocerebellar circuit properties in the absence of the voltage-gated potassium channels Kv3.1 and Kv3.3.

    PubMed

    McMahon, Anne; Fowler, Stephen C; Perney, Teresa M; Akemann, Walther; Knöpfel, Thomas; Joho, Rolf H

    2004-06-01

    Double-mutant mice (DKO) lacking the two voltage-gated K(+) channels Kv3.1 and Kv3.3 display a series of phenotypic alterations that include ataxia, myoclonus, tremor and alcohol hypersensitivity. The prominent cerebellar expression of mRNAs encoding Kv3.1 and Kv3.3 subunits raised the question as to whether altered electrical activity resulting from the lack of these K(+) channels might be related to the dramatic motor changes. We used the tremorogenic agent harmaline to probe mutant mice lacking different K(+) channel alleles for altered olivocerebellar circuit properties. Harmaline induced the characteristic 13-Hz tremor in wildtype mice (WT); however, no tremor was observed in DKO suggesting that the ensemble properties of the olivocerebellar circuitry are altered in the absence of Kv3.1 and Kv3.3 subunits. Harmaline induced tremor in Kv3.1-single mutants, but it was of smaller amplitude and at a lower frequency indicating the participation of Kv3.1 subunits in normal olivocerebellar system function. In contrast, harmaline tremor was virtually absent in Kv3.3-single mutants indicating an essential role for Kv3.3 subunits in tremor induction by harmaline. Immunohistochemical staining for Kv3.3 showed clear expression in the somata and proximal dendrites of Purkinje cells and in their axonal projections to the deep cerebellar nuclei (DCN). In DCN, both Kv3.1 and Kv3.3 subunits are expressed. Action potential duration is increased by approximately 100% in Purkinje cells from Kv3.3-single mutants compared to WT or Kv3.1-single mutants. We conclude that Kv3.3 channel subunits are essential for the olivocerebellar system to generate and sustain normal harmaline tremor whereas Kv3.1 subunits influence tremor amplitude and frequency.

  1. Motor dysfunction and altered synaptic transmission at the parallel fiber-Purkinje cell synapse in mice lacking potassium channels Kv3.1 and Kv3.3.

    PubMed

    Matsukawa, Hiroshi; Wolf, Alexander M; Matsushita, Shinichi; Joho, Rolf H; Knöpfel, Thomas

    2003-08-20

    Micelacking both Kv3.1 and both Kv3.3 K+ channel alleles display severe motor deficits such as tremor, myoclonus, and ataxic gait. Micelacking one to three alleles at the Kv3.1 and Kv3.3 loci exhibit in an allele dose-dependent manner a modest degree of ataxia. Cerebellar granule cells coexpress Kv3.1 and Kv3.3 K+ channels and are therefore candidate neurons that might be involved in these behavioral deficits. Hence, we investigated the synaptic mechanisms of transmission in the parallel fiber-Purkinje cell system. Action potentials of parallel fibers were broader in mice lacking both Kv3.1 and both Kv3.3 alleles and in mice lacking both Kv3.1 and a single Kv3.3 allele compared with those of wild-type mice. The transmission of high-frequency trains of action potentials was only impaired at 200 Hz but not at 100 Hz in mice lacking both Kv3.1 and Kv3.3 genes. However, paired-pulse facilitation (PPF) at parallel fiber-Purkinje cell synapses was dramatically reduced in a gene dose-dependent manner in mice lacking Kv3.1 or Kv3.3 alleles. Normal PPF could be restored by reducing the extracellular Ca2+ concentration indicating that increased activity-dependent presynaptic Ca2+ influx, at least in part caused the altered PPF in mutant mice. Induction of metabotropic glutamate receptor-mediated EPSCs was facilitated, whereas longterm depression was not impaired but rather facilitated in Kv3.1/Kv3.3 double-knockout mice. These results demonstrate the importance of Kv3 potassium channels in regulating the dynamics of synaptic transmission at the parallel fiber-Purkinje cell synapse and suggest a correlation between short-term plasticity at the parallel fiber-Purkinje cell synapse and motor performance.

  2. Kv7.5 Potassium Channel Subunits Are the Primary Targets for PKA-Dependent Enhancement of Vascular Smooth Muscle Kv7 Currents

    PubMed Central

    Mani, Bharath K.; Robakowski, Christina; Brueggemann, Lyubov I.; Cribbs, Leanne L.; Tripathi, Abhishek; Majetschak, Matthias

    2016-01-01

    Kv7 (KCNQ) channels, formed as homo- or heterotetramers of Kv7.4 and Kv7.5 α-subunits, are important regulators of vascular smooth muscle cell (VSMC) membrane voltage. Recent studies demonstrate that direct pharmacological modulation of VSMC Kv7 channel activity can influence blood vessel contractility and diameter. However, the physiologic regulation of Kv7 channel activity is still poorly understood. Here, we study the effect of cAMP/protein kinase A (PKA) activation on whole cell K+ currents through endogenous Kv7.5 channels in A7r5 rat aortic smooth muscle cells or through Kv7.4/Kv7.5 heteromeric channels natively expressed in rat mesenteric artery smooth muscle cells. The contributions of specific α-subunits are further dissected using exogenously expressed human Kv7.4 and Kv7.5 homo- or heterotetrameric channels in A7r5 cells. Stimulation of Gαs-coupled β-adrenergic receptors with isoproterenol induced PKA-dependent activation of endogenous Kv7.5 currents in A7r5 cells. The receptor-mediated enhancement of Kv7.5 currents was mimicked by pharmacological agents that increase [cAMP] (forskolin, rolipram, 3-isobutyl-1-methylxanthine, and papaverine) or mimic cAMP (8-bromo-cAMP); the 2- to 4-fold PKA-dependent enhancement of currents was also observed with exogenously expressed Kv7.5 channels. In contrast, exogenously-expressed heterotetrameric Kv7.4/7.5 channels in A7r5 cells or native mesenteric artery smooth muscle Kv7.4/7.5 channels were only modestly enhanced, and homo-tetrameric Kv7.4 channels were insensitive to this regulatory pathway. Correspondingly, proximity ligation assays indicated that isoproterenol induced PKA-dependent phosphorylation of exogenously expressed Kv7.5 channel subunits, but not of Kv7.4 subunits. These results suggest that signal transduction-mediated responsiveness of vascular smooth muscle Kv7 channel subunits to cAMP/PKA activation follows the order of Kv7.5 >> Kv7.4/Kv7.5 > Kv7.4. PMID:26700561

  3. Kv1.5 in the Immune System: the Good, the Bad, or the Ugly?

    PubMed Central

    Felipe, Antonio; Soler, Concepció; Comes, Núria

    2010-01-01

    For the last 20 years, knowledge of the physiological role of voltage-dependent potassium channels (Kv) in the immune system has grown exponentially. Leukocytes express a limited repertoire of Kv channels, which contribute to the membrane potential. These proteins are involved in the immune response and are therefore considered good pharmacological targets. Although there is a clear consensus about the physiological relevance of Kv1.3, the expression and the role of Kv1.5 are controversial. However, recent reports indicate that certain heteromeric Kv1.3/Kv1.5 associations may provide insight on Kv1.5. Here, we summarize what is known about this issue and highlight the role of Kv1.5 partnership interactions that could be responsible for this debate. The Kv1.3/Kv1.5 heterotetrameric composition of the channel and their possible differential associations with accessory regulatory proteins warrant further investigation. PMID:21423392

  4. Calculation of induced voltages on overhead lines caused by inclined lightning strokes

    SciTech Connect

    Sakakibara, A.

    1989-01-01

    Equations to calculate the inducing scalar and vector potentials produced by inclined return strokes are shown. Equations are also shown for calculating the induced voltages on overhead lines where horizontal components of inducing vector potential exist. The adequacy of the calculation method is demonstrated by field experiments. Using these equations, induced voltages on overhead lines are calculated for a variety of directions of return strokes.

  5. [Current concepts in the diagnosis and rehabilitation of the shoulder in overhead athletes].

    PubMed

    Gokeler, A; Lehmann, M; Knopf, E; Freiwald, J

    2003-03-01

    The purpose of this paper is to present the general guidelines, including implementation of principles of motor learning in the course of the rehabilitation of the shoulder in overhead athletes. The focus is on treating the most common injury pattern of overhead athletes being rotator cuff pathology with secondary bursitis and finally microtraumatic instability. Specific criteria are discussed to determine when the athlete can return to unrestricted sport participation.

  6. Comparison of Civilian and Military Overhead Spending: Three Case Studies. Revision.

    DTIC Science & Technology

    1984-09-17

    aDesignations used by the Defense Housing Management Systems Office. TABLE 4 CIVILIAN HOUSING MAINTENANCE SPENDING VS. AGEa (Single unit, owner occupied...I-t9 ONCOMlPARISON OF CIVILIRN iND MILITARY OVERHEAD SPENDING : ,l THREE CASE STUDIES.. (U) CENTER FOR NAVAL ANALYSES RLEXADRIA YR NAVAL PLRNNING RND...ftFL RESEARCH MEMORANDUM 0 COMPARISON OF CIVILIAN AND MILITARY OVERHEAD SPENDING : I THREE CASE STUDIES Daniel B. Levine Colin P. Hammon DTIC ELECTE K

  7. Kv3.1b and Kv3.3 channel subunit expression in murine spinal dorsal horn GABAergic interneurones.

    PubMed

    Nowak, A; Mathieson, H R; Chapman, R J; Janzsó, G; Yanagawa, Y; Obata, K; Szabo, G; King, A E

    2011-09-01

    GABAergic interneurones, including those within spinal dorsal horn, contain one of the two isoforms of the synthesizing enzyme glutamate decarboxylase (GAD), either GAD65 or GAD67. The physiological significance of these two GABAergic phenotypes is unknown but a more detailed anatomical and functional characterization may help resolve this issue. In this study, two transgenic Green Fluorescent Protein (GFP) knock-in murine lines, namely GAD65-GFP and GAD67-GFP (Δneo) mice, were used to profile expression of Shaw-related Kv3.1b and Kv3.3 K(+)-channel subunits in dorsal horn interneurones. Neuronal expression of these subunits confers specific biophysical characteristic referred to as 'fast-spiking'. Immuno-labelling for Kv3.1b or Kv3.3 revealed the presence of both of these subunits across the dorsal horn, most abundantly in laminae I-III. Co-localization studies in transgenic mice indicated that Kv3.1b but not Kv3.3 was associated with GAD65-GFP and GAD67-GFP immunopositive neurones. For comparison the distributions of Kv4.2 and Kv4.3 K(+)-channel subunits which are linked to an excitatory neuronal phenotype were characterized. No co-localization was found between GAD-GFP +ve neurones and Kv4.2 or Kv4.3. In functional studies to evaluate whether either GABAergic population is activated by noxious stimulation, hindpaw intradermal injection of capsaicin followed by c-fos quantification in dorsal horn revealed co-expression c-fos and GAD65-GFP (quantified as 20-30% of GFP +ve population). Co-expression was also detected for GAD67-GFP +ve neurones and capsaicin-induced c-fos but at a much reduced level of 4-5%. These data suggest that whilst both GAD65-GFP and GAD67-GFP +ve neurones express Kv3.1b and therefore may share certain biophysical traits, their responses to peripheral noxious stimulation are distinct.

  8. Adaptations of the Shoulder to Overhead Throwing in Youth Athletes

    PubMed Central

    Astolfi, Matthew Michael; Struminger, Aaron H.; Royer, Todd D.; Kaminski, Thomas W.; Swanik,, Charles B.

    2015-01-01

    Context The high number of repetitions and high forces associated with overhead throwing lead to anatomical adaptations, such as humeral retrotorsion and posterior-capsule thickness, in elite and professional baseball athletes. However, little is known about the origin and progression of these changes that may account for the increasing trend of chronic shoulder injuries in youth baseball and precipitate subsequent pathologic conditions throughout a young athlete's lifetime. Objective To investigate the relationship of age and upper extremity dominance on humeral retrotorsion, posterior-capsule thickness, and glenohumeral range of motion. Design Cross-sectional study. Setting Research laboratory, local baseball fields, and training facilities. Patients or Other Participants Thirty-six boys (mean age = 10.94 ± 1.34 years, height = 151.31 ± 12.17 cm, mass = 42.51 ± 10.32 kg) ranging in age from 8 to 12 years and involved in organized youth baseball. Main Outcome Measure(s) Diagnostic ultrasound was used to determine humeral retrotorsion and posterior-capsule thickness. Glenohumeral internal rotation and external rotation were measured using a handheld inclinometer. We used 2 × 2 mixed-model analyses of variance to compare the influence of limb dominance and age on the dependent variables of humeral retrotorsion, posterior-capsule thickness, internal rotation, and external rotation. Results The dominant shoulders of youth throwers exhibited less glenohumeral internal rotation but greater humeral retrotorsion, posterior-capsule thickness, and glenohumeral external rotation than the nondominant shoulders. Dominant internal rotation was greater in the 8- to 10-year-old group than in the 11- to 12-year-old group, and results trended toward a difference (F1,33 = 4.12, P = .05). Correlations existed between humeral retrotorsion and range of motion (P < .05). Conclusions The structural adaptations in the dominant shoulders of younger baseball players were similar to

  9. Postnatal development of A-type and Kv1- and Kv2-mediated potassium channel currents in neocortical pyramidal neurons

    PubMed Central

    Guan, Dongxu; Horton, Leslie R.; Armstrong, William E.

    2011-01-01

    Potassium channels regulate numerous aspects of neuronal excitability, and several voltage-gated K+ channel subunits have been identified in pyramidal neurons of rat neocortex. Previous studies have either considered the development of outward current as a whole or divided currents into transient, A-type and persistent, delayed rectifier components but did not differentiate between current components defined by α-subunit type. To facilitate comparisons of studies reporting K+ currents from animals of different ages and to understand the functional roles of specific current components, we characterized the postnatal development of identified Kv channel-mediated currents in pyramidal neurons from layers II/III from rat somatosensory cortex. Both the persistent/slowly inactivating and transient components of the total K+ current increased in density with postnatal age. We used specific pharmacological agents to test the relative contributions of putative Kv1- and Kv2-mediated currents (100 nM α-dendrotoxin and 600 nM stromatoxin, respectively). A combination of voltage protocol, pharmacology, and curve fitting was used to isolate the rapidly inactivating A-type current. We found that the density of all identified current components increased with postnatal age, approaching a plateau at 3–5 wk. We found no significant changes in the relative proportions or kinetics of any component between postnatal weeks 1 and 5, except that the activation time constant for A-type current was longer at 1 wk. The putative Kv2-mediated component was the largest at all ages. Immunocytochemistry indicated that protein expression for Kv4.2, Kv4.3, Kv1.4, and Kv2.1 increased between 1 wk and 4–5 wk of age. PMID:21451062

  10. Novel Kv3 glycoforms differentially expressed in adult mammalian brain contain sialylated N-glycans.

    PubMed

    Schwalbe, Ruth A; Corey, Melissa J; Cartwright, Tara A

    2008-02-01

    The N-glycan pool of mammalian brain contains remarkably high levels of sialylated N-glycans. This study provides the first evidence that voltage-gated K+ channels Kv3.1, Kv3.3, and Kv3.4, possess distinct sialylated N-glycan structures throughout the central nervous system of the adult rat. Electrophoretic migration patterns of Kv3.1, Kv3.3, and Kv3.4 glycoproteins from spinal cord, hypothalamus, thalamus, cerebral cortex, hippocampus, and cerebellum membranes digested with glycosidases were used to identify the various glycoforms. Differences in the migration of Kv3 proteins were attributed to the desialylated N-glycans. Expression levels of the Kv3 proteins were highest in cerebellum, whereas those of Kv3.1 and Kv3.3 were much lower in the other 5 regions. The lowest level of Kv3.1 was expressed in the hypothalamus, whereas the lowest levels of Kv3.3 were expressed in both thalamus and hypothalamus. The other regions expressed intermediate levels of Kv3.3, with spinal cord expressing the highest. The expression level of Kv3.4 in the hippocampus was slightly lower than that in cerebellum, and was closely followed by the other 4 regions, with spinal cord expressing the lowest level. We suggest that novel Kv3 glycoforms may endow differences in channel function and expression among regions throughout the central nervous system.

  11. Protein Kinase C (PKC) Activity Regulates Functional Effects of Kvβ1.3 Subunit on KV1.5 Channels

    PubMed Central

    David, Miren; Macías, Álvaro; Moreno, Cristina; Prieto, Ángela; Martínez-Mármol, Ramón; Vicente, Rubén; González, Teresa; Felipe, Antonio; Tamkun, Michael M.; Valenzuela, Carmen

    2012-01-01

    Kv1.5 channels are the primary channels contributing to the ultrarapid outward potassium current (IKur). The regulatory Kvβ1.3 subunit converts Kv1.5 channels from delayed rectifiers with a modest degree of slow inactivation to channels with both fast and slow inactivation components. Previous studies have shown that inhibition of PKC with calphostin C abolishes the fast inactivation induced by Kvβ1.3. In this study, we investigated the mechanisms underlying this phenomenon using electrophysiological, biochemical, and confocal microscopy approaches. To achieve this, we used HEK293 cells (which lack Kvβ subunits) transiently cotransfected with Kv1.5+Kvβ1.3 and also rat ventricular and atrial tissue to study native α-β subunit interactions. Immunocytochemistry assays demonstrated that these channel subunits colocalize in control conditions and after calphostin C treatment. Moreover, coimmunoprecipitation studies showed that Kv1.5 and Kvβ1.3 remain associated after PKC inhibition. After knocking down all PKC isoforms by siRNA or inhibiting PKC with calphostin C, Kvβ1.3-induced fast inactivation at +60 mV was abolished. However, depolarization to +100 mV revealed Kvβ1.3-induced inactivation, indicating that PKC inhibition causes a dramatic positive shift of the inactivation curve. Our results demonstrate that calphostin C-mediated abolishment of fast inactivation is not due to the dissociation of Kv1.5 and Kvβ1.3. Finally, immunoprecipitation and immunocytochemistry experiments revealed an association between Kv1.5, Kvβ1.3, the receptor for activated C kinase (RACK1), PKCβI, PKCβII, and PKCθ in HEK293 cells. A very similar Kv1.5 channelosome was found in rat ventricular tissue but not in atrial tissue. PMID:22547057

  12. MinK, MiRP1, and MiRP2 diversify Kv3.1 and Kv3.2 potassium channel gating.

    PubMed

    Lewis, Anthony; McCrossan, Zoe A; Abbott, Geoffrey W

    2004-02-27

    High frequency firing in mammalian neurons requires ultra-rapid delayed rectifier potassium currents generated by homomeric or heteromeric assemblies of Kv3.1 and Kv3.2 potassium channel alpha subunits. Kv3.1 alpha subunits can also form slower activating channels by coassembling with MinK-related peptide 2 (MiRP2), a single transmembrane domain potassium channel ancillary subunit. Here, using channel subunits cloned from rat and expressed in Chinese hamster ovary cells, we show that modulation by MinK, MiRP1, and MiRP2 is a general mechanism for slowing of Kv3.1 and Kv3.2 channel activation and deactivation and acceleration of inactivation, creating a functionally diverse range of channel complexes. MiRP1 also negatively shifts the voltage dependence of Kv3.1 and Kv3.2 channel activation. Furthermore, MinK, MiRP1, and MiRP2 each form channels with Kv3.1-Kv3.2 heteromers that are kinetically distinct from one another and from MiRP/homomeric Kv3 channels. The findings illustrate a mechanism for dynamic expansion of the functional repertoire of Kv3.1 and Kv3.2 potassium currents and suggest roles for these alpha subunits outside the scope of sustained rapid neuronal firing.

  13. Kv2 subunits underlie slowly inactivating potassium current in rat neocortical pyramidal neurons

    PubMed Central

    Guan, D; Tkatch, T; Surmeier, D J; Armstrong, W E; Foehring, R C

    2007-01-01

    We determined the expression of Kv2 channel subunits in rat somatosensory and motor cortex and tested for the contributions of Kv2 subunits to slowly inactivating K+ currents in supragranular pyramidal neurons. Single cell RT-PCR showed that virtually all pyramidal cells expressed Kv2.1 mRNA and ∼80% expressed Kv2.2 mRNA. Immunocytochemistry revealed striking differences in the distribution of Kv2.1 and Kv2.2 subunits. Kv2.1 subunits were clustered and located on somata and proximal dendrites of all pyramidal cells. Kv2.2 subunits were primarily distributed on large apical dendrites of a subset of pyramidal cells from deep layers. We used two methods for isolating currents through Kv2 channels after excluding contributions from Kv1 subunits: intracellular diffusion of Kv2.1 antibodies through the recording pipette and extracellular application of rStromatoxin-1 (ScTx). The Kv2.1 antibody specifically blocked the slowly inactivating K+ current by 25–50% (at 8 min), demonstrating that Kv2.1 subunits underlie much of this current in neocortical pyramidal neurons. ScTx (300 nm) also inhibited ∼40% of the slowly inactivating K+ current. We observed occlusion between the actions of Kv2.1 antibody and ScTx. In addition, Kv2.1 antibody- and ScTx-sensitive currents demonstrated similar recovery from inactivation and voltage dependence and kinetics of activation and inactivation. These data indicate that both agents targeted the same channels. Considering the localization of Kv2.1 and 2.2 subunits, currents from truncated dissociated cells are probably dominated by Kv2.1 subunits. Compared with Kv2.1 currents in expression systems, the Kv2.1 current in neocortical pyramidal cells activated and inactivated at relatively negative potentials and was very sensitive to holding potential. PMID:17379638

  14. Skeletal muscle Kv7 (KCNQ) channels in myoblast differentiation and proliferation

    SciTech Connect

    Roura-Ferrer, Meritxell; Sole, Laura; Martinez-Marmol, Ramon; Villalonga, Nuria; Felipe, Antonio

    2008-05-16

    Voltage-dependent K{sup +} channels (Kv) are involved in myocyte proliferation and differentiation by triggering changes in membrane potential and regulating cell volume. Since Kv7 channels may participate in these events, the purpose of this study was to investigate whether skeletal muscle Kv7.1 and Kv7.5 were involved during proliferation and myogenesis. Here we report that, while myotube formation did not regulate Kv7 channels, Kv7.5 was up-regulated during cell cycle progression. Although, Kv7.1 mRNA also increased during the G{sub 1}-phase, pharmacological evidence mainly involves Kv7.5 in myoblast growth. Our results indicate that the cell cycle-dependent expression of Kv7.5 is involved in skeletal muscle cell proliferation.

  15. Kv3.3 potassium channels and spinocerebellar ataxia.

    PubMed

    Zhang, Yalan; Kaczmarek, Leonard K

    2016-08-15

    The voltage-dependent potassium channel subunit Kv3.3 is expressed at high levels in cerebellar Purkinje cells, in auditory brainstem nuclei and in many other neurons capable of firing at high rates. In the cerebellum, it helps to shape the very characteristic complex spike of Purkinje cells. Kv3.3 differs from other closely related channels in that human mutations in the gene encoding Kv3.3 (KCNC3) result in a unique neurodegenerative disease termed spinocerebellar ataxia type 13 (SCA13). This primarily affects the cerebellum, but also results in extracerebellar symptoms. Different mutations produce either early onset SCA13, associated with delayed motor and impaired cognitive skill acquisition, or late onset SCA13, which typically produces cerebellar degeneration in middle age. This review covers the localization and physiological function of Kv3.3 in the central nervous system and how the normal function of the channel is altered by the disease-causing mutations. It also describes experimental approaches that are being used to understand how Kv3.3 mutations are linked to neuronal survival, and to develop strategies for treatment.

  16. Comparison of a 250 kV single-stage accelerator mass spectrometer with a 5 MV tandem accelerator mass spectrometer--fitness for purpose in bioanalysis.

    PubMed

    Young, G C; Corless, S; Felgate, C C; Colthup, P V

    2008-12-01

    The introduction of 'compact' accelerator mass spectrometers into biomedical science, including use in drug metabolism and bioanalytical applications, is an exciting recent development. Comparisons are presented here between a more established and relatively large tandem accelerator which operates at up to 5 MV and a conventional laboratory-sized 250 kV single-stage accelerator mass spectrometer. Biological samples were enriched with low levels of radiocarbon, then converted into graphite prior to analysis on each of the two instruments. The data obtained showed the single-stage instrument to be capable of delivering comparable results, and thus able to provide similar study support, with that provided by the 5 MV instrument, without the significant overheads and complexities which are inherent to the operation of the larger instrument. We believe that the advent of these laboratory-sized accelerator mass spectrometry (AMS) instruments represents a real turning point in the potential for application of AMS by a wider user group.

  17. Effects of overhead work configuration on muscle activity during a simulated drilling task.

    PubMed

    Maciukiewicz, Jacquelyn M; Cudlip, Alan C; Chopp-Hurley, Jaclyn N; Dickerson, Clark R

    2016-03-01

    Overhead work is a known catalyst for occupational shoulder injury. Industrial workers must often adopt awkward overhead postures and loading profiles to complete required tasks, potentially elevating injury risk. This research examined the combined influence of multiple overhead working parameters on upper extremity muscular demands for an industrial drilling application. Twenty-two right-handed males completed 24 unilateral and bilateral overhead work exertions stratified by direction (upward, forward), point of force application (15, 30 and 45 cm in front of the body), and whole-body posture (seated, standing). The dependency of electromyographic (EMG) activity on several factors was established. Significant two-way interactions existed between point of force application and direction (p < 0.0001) and direction and whole body posture (p < 0.0001). An average increase in muscular activity of 6.5% maximal voluntary contraction (MVC) occurred for the contralateral limb when the bilateral task was completed, compared to unilateral tasks, with less than a 1% MVC increase for the active limb. These findings assist evidence-based approaches to overhead tasks, specifically in the construction industry. A bilateral task configuration is recommended to reduce glenohumeral stability demands. As well, particularly for tasks with a far reach distance, design tasks to promote a forward directed exertion. The considerable inter-subject variability suggests that fixed heights are not ideal, and should be avoided, and where this is not possible reaches should be reduced.

  18. Two-Level Incremental Checkpoint Recovery Scheme for Reducing System Total Overheads

    PubMed Central

    Li, Huixian; Pang, Liaojun; Wang, Zhangquan

    2014-01-01

    Long-running applications are often subject to failures. Once failures occur, it will lead to unacceptable system overheads. The checkpoint technology is used to reduce the losses in the event of a failure. For the two-level checkpoint recovery scheme used in the long-running tasks, it is unavoidable for the system to periodically transfer huge memory context to a remote stable storage. Therefore, the overheads of setting checkpoints and the re-computing time become a critical issue which directly impacts the system total overheads. Motivated by these concerns, this paper presents a new model by introducing i-checkpoints into the existing two-level checkpoint recovery scheme to deal with the more probable failures with the smaller cost and the faster speed. The proposed scheme is independent of the specific failure distribution type and can be applied to different failure distribution types. We respectively make analyses between the two-level incremental and two-level checkpoint recovery schemes with the Weibull distribution and exponential distribution, both of which fit with the actual failure distribution best. The comparison results show that the total overheads of setting checkpoints, the total re-computing time and the system total overheads in the two-level incremental checkpoint recovery scheme are all significantly smaller than those in the two-level checkpoint recovery scheme. At last, limitations of our study are discussed, and at the same time, open questions and possible future work are given. PMID:25111048

  19. ACUTE EFFECTS OF DIFFERENT SELF‐MASSAGE VOLUMES ON THE FMS™ OVERHEAD DEEP SQUAT PERFORMANCE

    PubMed Central

    Škarabot, Jakob; Vigotsky, Andrew D; Brown, Amanda Fernandes; Gomes, Thiago Matassoli; Novaes, Jefferson da Silva

    2017-01-01

    Background The Functional Movement Screen (FMS™) is a battery of tests designed to assess movement competency; the overhead deep squat test, specifically, has been shown to be an accurate predictor of overall FMS™ scores. Self‐massage (SM) is a ubiquitous warm‐up utilized to increase joint range of motion and, therefore, may be effective for improving performance of the overhead deep squat test. Purpose To examine how different doses (30, 60, 90, and 120 seconds) of SM of different areas of the body (plantar fascia, latissimus dorsi, and lateral thigh) affects the score obtained on an overhead deep squat test. Methods Twenty recreationally active females were recruited to be tested on four occasions: sessions one and two consisted of baseline testing, session three consisted of SM applied to the lateral thigh, and session four consisted of SM applied to the lateral torso and plantar fascia. Results In all SM conditions, at least 90 seconds was required for a change in deep squat score from baseline; therefore, it is concluded that SM the lateral torso, plantar fascia, and lateral thigh for 90 seconds or more are effective interventions for acutely improving overhead deep squat scores. Conclusion Self‐massage appears to be an effective modality for inducing acute improvements in the performance of the FMS™ overhead deep squat in all conditions tested. Level of evidence 2b PMID:28217420

  20. Ablation of Kv3.1 and Kv3.3 potassium channels disrupts thalamocortical oscillations in vitro and in vivo.

    PubMed

    Espinosa, Felipe; Torres-Vega, Miguel A; Marks, Gerald A; Joho, Rolf H

    2008-05-21

    The genes Kcnc1 and Kcnc3 encode the subunits for the fast-activating/fast-deactivating, voltage-gated potassium channels Kv3.1 and Kv3.3, which are expressed in several brain regions known to be involved in the regulation of the sleep-wake cycle. When these genes are genetically eliminated, Kv3.1/Kv3.3-deficient mice display severe sleep loss as a result of unstable slow-wave sleep. Within the thalamocortical circuitry, Kv3.1 and Kv3.3 subunits are highly expressed in the thalamic reticular nucleus (TRN), which is thought to act as a pacemaker at sleep onset and to be involved in slow oscillatory activity (spindle waves) during slow-wave sleep. We showed that in cortical electroencephalographic recordings of freely moving Kv3.1/Kv3.3-deficient mice, spectral power is reduced up to 70% at frequencies <15 Hz. In addition, the number of sleep spindles in vivo as well as rhythmic rebound firing of TRN neurons in vitro is diminished in mutant mice. Kv3.1/Kv3.3-deficient TRN neurons studied in vitro show approximately 60% increase in action potential duration and a reduction in high-frequency firing after depolarizing current injections and during rebound burst firing. The results support the hypothesis that altered electrophysiological properties of TRN neurons contribute to the reduced EEG power at slow frequencies in the thalamocortical network of Kv3-deficient mice.

  1. The role of Kv3-type potassium channels in cerebellar physiology and behavior.

    PubMed

    Joho, Rolf H; Hurlock, Edward C

    2009-09-01

    Different subunits of the Kv3 subfamily of voltage-gated potassium (Kv) channels (Kv3.1-Kv3.4) are expressed in distinct neuronal subpopulations in the cerebellum. Behavioral phenotypes in Kv3-null mutant mice such as ataxia with prominent hypermetria and heightened alcohol sensitivity are characteristic of cerebellar dysfunction. Here, we review how the unique biophysical properties of Kv3-type potassium channels, fast activation and fast deactivation that enable cerebellar neurons to generate brief action potentials at high frequencies, affect firing patterns and influence cerebellum-mediated behavior.

  2. Kv3.4 subunits enhance the repolarizing efficiency of Kv3.1 channels in fast-spiking neurons.

    PubMed

    Baranauskas, Gytis; Tkatch, Tatiana; Nagata, Keiichi; Yeh, Jay Z; Surmeier, D James

    2003-03-01

    Neurons with the capacity to discharge at high rates--'fast-spiking' (FS) neurons--are critical participants in central motor and sensory circuits. It is widely accepted that K+ channels with Kv3.1 or Kv3.2 subunits underlie fast, delayed-rectifier (DR) currents that endow neurons with this FS ability. Expression of these subunits in heterologous systems, however, yields channels that open at more depolarized potentials than do native Kv3 family channels, suggesting that they differ. One possibility is that native channels incorporate a subunit that modifies gating. Molecular, electrophysiological and pharmacological studies reported here suggest that a splice variant of the Kv3.4 subunit coassembles with Kv3.1 subunits in rat brain FS neurons. Coassembly enhances the spike repolarizing efficiency of the channels, thereby reducing spike duration and enabling higher repetitive spike rates. These results suggest that manipulation of K3.4 subunit expression could be a useful means of controlling the dynamic range of FS neurons.

  3. Position-dependent attenuation by Kv1.6 of N-type inactivation of Kv1.4-containing channels.

    PubMed

    Al-Sabi, Ahmed; Kaza, Seshu; Le Berre, Marie; O'Hara, Liam; Bodeker, MacDara; Wang, Jiafu; Dolly, J Oliver

    2011-09-01

    Assembly of distinct α subunits of Kv1 (voltage-gated K(+) channels) into tetramers underlies the diversity of their outward currents in neurons. Kv1.4-containing channels normally exhibit N-type rapid inactivation, mediated through an NIB (N-terminal inactivation ball); this can be over-ridden if associated with a Kv1.6 α subunit, via its NIP (N-type inactivation prevention) domain. Herein, NIP function was shown to require positioning of Kv1.6 adjacent to the Kv1.4 subunit. Using a recently devised gene concatenation, heterotetrameric Kv1 channels were expressed as single-chain proteins on the plasmalemma of HEK (human embryonic kidney)-293 cells, so their constituents could be arranged in different positions. Placing the Kv1.4 and 1.6 genes together, followed by two copies of Kv1.2, yielded a K(+) current devoid of fast inactivation. Mutation of critical glutamates within the NIP endowed rapid inactivation. Moreover, separating Kv1.4 and 1.6 with a copy of Kv1.2 gave a fast-inactivating K(+) current with steady-state inactivation shifted to more negative potentials and exhibiting slower recovery, correlating with similar inactivation kinetics seen for Kv1.4-(1.2)(3). Alternatively, separating Kv1.4 and 1.6 with two copies of Kv1.2 yielded slow-inactivating currents, because in this concatamer Kv1.4 and 1.6 should be together. These findings also confirm that the gene concatenation can generate K(+) channels with α subunits in pre-determined positions.

  4. Communication overhead on the Intel Paragon, IBM SP2 and Meiko CS-2

    NASA Technical Reports Server (NTRS)

    Bokhari, Shahid H.

    1995-01-01

    Interprocessor communication overhead is a crucial measure of the power of parallel computing systems-its impact can severely limit the performance of parallel programs. This report presents measurements of communication overhead on three contemporary commercial multicomputer systems: the Intel Paragon, the IBM SP2 and the Meiko CS-2. In each case the time to communicate between processors is presented as a function of message length. The time for global synchronization and memory access is discussed. The performance of these machines in emulating hypercubes and executing random pairwise exchanges is also investigated. It is shown that the interprocessor communication time depends heavily on the specific communication pattern required. These observations contradict the commonly held belief that communication overhead on contemporary machines is independent of the placement of tasks on processors. The information presented in this report permits the evaluation of the efficiency of parallel algorithm implementations against standard baselines.

  5. Behavioral motor dysfunction in Kv3-type potassium channel-deficient mice.

    PubMed

    Joho, R H; Street, C; Matsushita, S; Knöpfel, T

    2006-08-01

    The voltage-gated potassium channels Kv3.1 and Kv3.3 are expressed in several distinct neuronal subpopulations in brain areas known to be involved in motor control such as cortex, basal ganglia and cerebellum. Depending on the lack of Kv3.1 or Kv3.3 channel subunits, mutant mice show different Kv3-null allele-dependent behavioral alterations that include constitutive hyperactivity, sleep loss, impaired motor performance and, in the case of the Kv3.1/Kv3.3 double mutant, also severe ataxia, tremor and myoclonus (Espinosa et al. 2001, J Neurosci 21, 6657-6665, Genes, Brain Behav 3, 90-100). The lack of Kv3.1 channel subunits is mainly responsible for the constitutively increased locomotor activity and for sleep loss, whereas the absence of Kv3.3 subunits affects cerebellar function, in particular Purkinje cell discharges and olivocerebellar system properties (McMahon et al. 2004, Eur J Neurosci 19, 3317-3327). Here, we describe two sensitive and non-invasive tests to reliably quantify normal and abnormal motor functions, and we apply these tests to characterize motor dysfunction in Kv3-mutant mice. In contrast to wildtype and Kv3.1-single mutants, Kv3.3-single mutants and Kv3 mutants lacking three and four Kv3 alleles display Kv3-null allele-dependent gait alterations. Although the Kv3-null allele-dependent gait changes correlate with reduced motor performance, they appear to not affect the training-induced improvement of motor performance. These findings suggest that altered cerebellar physiology in the absence of Kv3.3 channels is responsible for impaired motor task execution but not motor task learning.

  6. Alternative splicing regulates kv3.1 polarized targeting to adjust maximal spiking frequency.

    PubMed

    Gu, Yuanzheng; Barry, Joshua; McDougel, Robert; Terman, David; Gu, Chen

    2012-01-13

    Synaptic inputs received at dendrites are converted into digital outputs encoded by action potentials generated at the axon initial segment in most neurons. Here, we report that alternative splicing regulates polarized targeting of Kv3.1 voltage-gated potassium (Kv) channels to adjust the input-output relationship. The spiking frequency of cultured hippocampal neurons correlated with the level of endogenous Kv3 channels. Expression of axonal Kv3.1b, the longer form of Kv3.1 splice variants, effectively converted slow-spiking young neurons to fast-spiking ones; this was not the case for Kv1.2 or Kv4.2 channel constructs. Despite having identical biophysical properties as Kv3.1b, dendritic Kv3.1a was significantly less effective at increasing the maximal firing frequency. This suggests a possible role of channel targeting in regulating spiking frequency. Mutagenesis studies suggest the electrostatic repulsion between the Kv3.1b N/C termini, created by its C-terminal splice domain, unmasks the Kv3.1b axonal targeting motif. Kv3.1b axonal targeting increased the maximal spiking frequency in response to prolonged depolarization. This finding was further supported by the results of local application of channel blockers and computer simulations. Taken together, our studies have demonstrated that alternative splicing controls neuronal firing rates by regulating the polarized targeting of Kv3.1 channels.

  7. Increased motor drive and sleep loss in mice lacking Kv3-type potassium channels.

    PubMed

    Espinosa, F; Marks, G; Heintz, N; Joho, R H

    2004-04-01

    The voltage-gated potassium channels Kv3.1 and Kv3.3 are widely expressed in the brain, including areas implicated in the control of motor activity and in areas thought to regulate arousal states. Although Kv3.1 and Kv3.3-single mutants show some physiological changes, previous studies revealed relatively subtle behavioral alterations suggesting that Kv3.1 and Kv3.3 channel subunits may be encoded by a pair of redundant genes. In agreement with this hypothesis, Kv3.1/Kv3.3-deficient mice display a 'strong' mutant phenotype that includes motor dysfunction (ataxia, myoclonus, tremor) and hyperactivity when exposed to a novel environment. In this paper we report that Kv3.1/Kv3.3-deficient mice are also constitutively hyperactive. Compared to wildtype mice, double mutants display 'restlessness' that is particularly prominent during the light period, when mice are normally at rest, characterized by more than a doubling of ambulatory and stereotypic activity, and accompanied by a 40% sleep reduction. When we reinvestigated both single mutants, we observed constitutive increases of ambulatory and stereotypic activity in conjunction with sleep loss in Kv3.1-single mutants but not in Kv3.3-single mutants. These findings indicate that the absence of Kv3.1-channel subunits is primarily responsible for the increased motor drive and the reduction in sleep time.

  8. Nitrate leaching beneath a containerized nursery crop receiving trickle or overhead irrigation.

    PubMed

    Colangelo, D J; Brand, M H

    2001-01-01

    Container production of nursery crops is intensive and a potential source of nitrogen release to the environment. This study was conducted to determine if trickle irrigation could be used by container nursery producers as an alternative to standard overhead irrigation to reduce nitrogen release into the environment. The effect of overhead irrigation and trickle irrigation on leachate nitrate N concentration, flow-weighted nitrate N concentration, leachate volume, and plant growth was investigated using containerized rhododendron (Rhododendron catawbiense Michx. 'Album') supplied with a controlled-release fertilizer and grown outdoors on top of soil-monolith lysimeters. Leachate was collected over two growing seasons and overwinter periods, and natural precipitation was allowed as a component of the system. Precipitation accounted for 69% of the water entering the overhead-irrigated system and 80% of the water entering the trickle-irrigated system. Leachate from fertilized plants exceeded the USEPA limit of 10 mg L(-1) at several times and reached a maximum of 26 mg L(-1) with trickle irrigation. Average annual loss of nitrate N in leachate for fertilized treatments was 51.8 and 60.5 kg ha(-1) for the overhead and trickle treatments, respectively. Average annual flow-weighted concentration of nitrate N in leachate of fertilized plants was 7.2 mg L(-1) for overhead irrigation and 12.7 mg L(-1) for trickle irrigation. Trickle irrigation did not reduce the amount of nitrate N leached from nursery containers when compared with overhead irrigation because precipitation nullified the potential benefits of reduced leaching fractions and irrigation inputs provided under trickle irrigation.

  9. The use of polymer horizontal vee arms for 120kV to 230kV conversion

    SciTech Connect

    Doubley, D. )

    1991-01-01

    This paper reports on Detroit Edison which is using the horizontal-vee configuration to convert 120 kV tower lines to 230 kV. This approach is an improvement over previous methods of existing line conversion. The design provides reduced construction costs; both in labor and material. It also provides improvement in line structure strength as well. The all polymer horizontal-vees as replacement for crossarms on existing towers make a substantial improvement in productivity. They are lighter, easier to handle, and less likely to break than their porcelain equivalents.

  10. Selective underexpression of Kv3.2 and Kv3.4 channels in the cortex of rats exposed to ethanol during early postnatal life.

    PubMed

    Tavian, Daniela; De Giorgio, Andrea; Granato, Alberto

    2011-08-01

    The expression of voltage-gated potassium channels belonging to the Kv3 family has been studied in the sensori-motor cortex of rats exposed to alcohol inhalation during the first postnatal week (P2-P6). The study was carried out using comparative RT-PCR. At P9, a significant reduction of the expression of Kv3.2 and Kv3.4 subunits occurred in alcohol-treated animals, as compared with controls. The expression of the Kv3.4a splicing variant, which is thought to be critically involved in the high-frequency firing of some cortical interneurons, was also correspondingly reduced. The downregulation of Kv3.2 and Kv3.4a subunits represented a long-lasting effect of alcohol exposure, since it was also observed in P24 animals. The expression of both Kv3.1 and Kv3.3 channels appeared to be not significantly affected by alcohol exposure. An increased susceptibility to apoptotic neuronal death after early postnatal exposure to ethanol was confirmed by the lower bcl-2/bax ratio observed in alcohol-treated animals. Although Kv3.4 subunits are thought to trigger apoptosis, the lack of upregulation in our model argues against their involvement in the mechanism leading to alcohol-induced apoptosis. The possible consequences of the selective downregulation of Kv3 subunits on the cortical function, as well as their relevance for the genesis of fetal alcohol effects, are discussed.

  11. Kv4.2 Knockout Mice Have Hippocampal-Dependent Learning and Memory Deficits

    ERIC Educational Resources Information Center

    Lugo, Joaquin N.; Brewster, Amy L.; Spencer, Corinne M.; Anderson, Anne E.

    2012-01-01

    Kv4.2 channels contribute to the transient, outward K[superscript +] current (A-type current) in hippocampal dendrites, and modulation of this current substantially alters dendritic excitability. Using Kv4.2 knockout (KO) mice, we examined the role of Kv4.2 in hippocampal-dependent learning and memory. We found that Kv4.2 KO mice showed a deficit…

  12. Distribution of Kv3.3 potassium channel subunits in distinct neuronal populations of mouse brain.

    PubMed

    Chang, Su Ying; Zagha, Edward; Kwon, Elaine S; Ozaita, Andres; Bobik, Marketta; Martone, Maryann E; Ellisman, Mark H; Heintz, Nathaniel; Rudy, Bernardo

    2007-06-20

    Kv3.3 proteins are pore-forming subunits of voltage-dependent potassium channels, and mutations in the gene encoding for Kv3.3 have recently been linked to human disease, spinocerebellar ataxia 13, with cerebellar and extracerebellar symptoms. To understand better the functions of Kv3.3 subunits in brain, we developed highly specific antibodies to Kv3.3 and analyzed immunoreactivity throughout mouse brain. We found that Kv3.3 subunits are widely expressed, present in important forebrain structures but particularly prominent in brainstem and cerebellum. In forebrain and midbrain, Kv3.3 expression was often found colocalized with parvalbumin and other Kv3 subunits in inhibitory neurons. In brainstem, Kv3.3 was strongly expressed in auditory and other sensory nuclei. In cerebellar cortex, Kv3.3 expression was found in Purkinje and granule cells. Kv3.3 proteins were observed in axons, terminals, somas, and, unlike other Kv3 proteins, also in distal dendrites, although precise subcellular localization depended on cell type. For example, hippocampal dentate granule cells expressed Kv3.3 subunits specifically in their mossy fiber axons, whereas Purkinje cells of the cerebellar cortex strongly expressed Kv3.3 subunits in axons, somas, and proximal and distal, but not second- and third-order, dendrites. Expression in Purkinje cell dendrites was confirmed by immunoelectron microscopy. Kv3 channels have been demonstrated to rapidly repolarize action potentials and support high-frequency firing in various neuronal populations. In this study, we identified additional populations and subcellular compartments that are likely to sustain high-frequency firing because of the expression of Kv3.3 and other Kv3 subunits.

  13. Molecular and functional characterization of Kv7 K+ channel in murine gastrointestinal smooth muscles.

    PubMed

    Jepps, Thomas A; Greenwood, Iain A; Moffatt, James D; Sanders, Kenton M; Ohya, Susumu

    2009-07-01

    Members of the K(v)7 voltage-gated K(+) channel family are important determinants of cardiac and neuronal membrane excitability. Recently, we and others have shown that K(v)7 channels are also crucial regulators of smooth muscle activity. The aim of the present study was to assess the K(v)7 expression in different parts of the murine gastrointestinal (GI) tract and to assess their functional roles by use of pharmacological agents. Of KCNQ/K(v)7 members, both KCNQ4/K(v)7.4 and KCNQ5/K(v)7.5 genes and proteins were the most abundantly expressed K(v)7 channels in smooth muscles throughout the GI tract. Immunohistochemical staining also revealed that K(v)7.4 and K(v)7.5 but not K(v)7.1 were expressed in the circular muscle layer of the colon. In segments of distal colon circular muscle exhibiting spontaneous phasic contractions, the nonselective K(v)7 blockers XE991 and linopirdine increased the integral of tension. Increases in the integral of tension were also observed under conditions of neuronal blockade. Similar effects, although less marked, were observed in the proximal colon. As expected, the K(v)7.1-selective blocker chromanol 293B had no effect in either type of segment. These data show that K(v)7.x especially K(v)7.4 and K(v)7.5 are expressed in different regions of the murine gastrointestinal tract and blockers of K(v)7 channels augment inherent contractile activity. Drugs that selectively block K(v)7.4/7.5 might be promising therapeutics for the treatment of motility disorders such as constipation associated with irritable bowel syndrome.

  14. Buffalo Flat Service 115-KV Transmission Project : Environmental Assessment.

    SciTech Connect

    United States. Bonneville Power Administration.

    1987-07-01

    The US Air Force has sited a radar transmitter at Buffalo Flat, near Christmas Valley, Oregon. This report discusses the environmental impacts of providing the electrical service for the installation. A 115 kV power transmission line will be built between LaPine and Buffalo Flat. Route alternatives as well as design alternatives are discussed. (ACR)

  15. The contribution of Kv2.2-mediated currents decreases during the postnatal development of mouse dorsal root ganglion neurons.

    PubMed

    Regnier, Glenn; Bocksteins, Elke; Van de Vijver, Gerda; Snyders, Dirk J; van Bogaert, Pierre-Paul

    2016-03-01

    Delayed rectifier voltage-gated K(+)(Kv) channels play an important role in the regulation of the electrophysiological properties of neurons. In mouse dorsal root ganglion (DRG) neurons, a large fraction of the delayed rectifier current is carried by both homotetrameric Kv2 channels and heterotetrameric channels consisting of Kv2 and silent Kv (KvS) subunits (i.e., Kv5-Kv6 and Kv8-Kv9). However, little is known about the contribution of Kv2-mediated currents during the postnatal development ofDRGneurons. Here, we report that the Stromatoxin-1 (ScTx)-sensitive fraction of the total outward K(+)current (IK) from mouseDRGneurons gradually decreased (~13%,P < 0.05) during the first month of postnatal development. Because ScTx inhibits both Kv2.1- and Kv2.2-mediated currents, this gradual decrease may reflect a decrease in currents containing either subunit. However, the fraction of Kv2.1 antibody-sensitive current that only reflects the Kv2.1-mediated currents remained constant during that same period. These results suggested that the fractional contribution of Kv2.2-mediated currents relative toIKdecreased with postnatal age. SemiquantitativeRT-PCRanalysis indicated that this decrease can be attributed to developmental changes in Kv2.2 expression as themRNAlevels of the Kv2.2 subunit decreased gradually between 1 and 4 weeks of age. In addition, we observed age-dependent fluctuations in themRNAlevels of the Kv6.3, Kv8.1, Kv9.1, and Kv9.3 subunits. These results support an important role of both Kv2 and KvS subunits in the postnatal maturation ofDRGneurons.

  16. Kv1 channels and neural processing in vestibular calyx afferents

    PubMed Central

    Meredith, Frances L.; Kirk, Matthew E.; Rennie, Katherine J.

    2015-01-01

    Potassium-selective ion channels are important for accurate transmission of signals from auditory and vestibular sensory end organs to their targets in the central nervous system. During different gravity conditions, astronauts experience altered input signals from the peripheral vestibular system resulting in sensorimotor dysfunction. Adaptation to altered sensory input occurs, but it is not explicitly known whether this involves synaptic modifications within the vestibular epithelia. Future investigations of such potential plasticity require a better understanding of the electrophysiological mechanisms underlying the known heterogeneity of afferent discharge under normal conditions. This study advances this understanding by examining the role of the Kv1 potassium channel family in mediating action potentials in specialized vestibular afferent calyx endings in the gerbil crista and utricle. Pharmacological agents selective for different sub-types of Kv1 channels were tested on membrane responses in whole cell recordings in the crista. Kv1 channels sensitive to α-dendrotoxin and dendrotoxin-K were found to prevail in the central regions, whereas K+ channels sensitive to margatoxin, which blocks Kv1.3 and 1.6 channels, were more prominent in peripheral regions. Margatoxin-sensitive currents showed voltage-dependent inactivation. Dendrotoxin-sensitive currents showed no inactivation and dampened excitability in calyces in central neuroepithelial regions. The differential distribution of Kv1 potassium channels in vestibular afferents supports their importance in accurately relaying gravitational and head movement signals through specialized lines to the central nervous system. Pharmacological modulation of specific groups of K+ channels could help alleviate vestibular dysfunction on earth and in space. PMID:26082693

  17. 49 CFR 214.515 - Overhead covers for existing on-track roadway maintenance machines.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... maintenance machines. 214.515 Section 214.515 Transportation Other Regulations Relating to Transportation... Roadway Maintenance Machines and Hi-Rail Vehicles § 214.515 Overhead covers for existing on-track roadway maintenance machines. (a) For those existing on-track roadway maintenance machines either currently...

  18. 49 CFR 214.515 - Overhead covers for existing on-track roadway maintenance machines.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... maintenance machines. 214.515 Section 214.515 Transportation Other Regulations Relating to Transportation... Roadway Maintenance Machines and Hi-Rail Vehicles § 214.515 Overhead covers for existing on-track roadway maintenance machines. (a) For those existing on-track roadway maintenance machines either currently...

  19. 49 CFR 214.515 - Overhead covers for existing on-track roadway maintenance machines.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... maintenance machines. 214.515 Section 214.515 Transportation Other Regulations Relating to Transportation... Roadway Maintenance Machines and Hi-Rail Vehicles § 214.515 Overhead covers for existing on-track roadway maintenance machines. (a) For those existing on-track roadway maintenance machines either currently...

  20. 49 CFR 214.515 - Overhead covers for existing on-track roadway maintenance machines.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... maintenance machines. 214.515 Section 214.515 Transportation Other Regulations Relating to Transportation... Roadway Maintenance Machines and Hi-Rail Vehicles § 214.515 Overhead covers for existing on-track roadway maintenance machines. (a) For those existing on-track roadway maintenance machines either currently...

  1. 49 CFR 214.515 - Overhead covers for existing on-track roadway maintenance machines.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... maintenance machines. 214.515 Section 214.515 Transportation Other Regulations Relating to Transportation... Roadway Maintenance Machines and Hi-Rail Vehicles § 214.515 Overhead covers for existing on-track roadway maintenance machines. (a) For those existing on-track roadway maintenance machines either currently...

  2. 45. MACHINE SHOP NORTH/NORTHEAST INCLUDING OVERHEAD LINE SHAFTING. MOSTLY BELT ...

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

    45. MACHINE SHOP NORTH/NORTHEAST INCLUDING OVERHEAD LINE SHAFTING. MOSTLY BELT DRIVEN WITH ONE ROPE DRIVEN LATHE IN MIDDLE GROUND. POWER COMES FROM KNIGHT TURBINE ON FAR WALL SHOWN IN K-77, 78 (42') - Knight Foundry, 13 Eureka Street, Sutter Creek, Amador County, CA

  3. Redesigning the rural health center: high tech, high touch, and low overhead.

    PubMed

    Crane, Steven

    2011-01-01

    To attract new physicians to rural primary care, new models of care are needed that are more effective, more sustainable, and replicable in smaller communities. This commentary provides a brief description of preliminary findings associated with a radically redesigned, low-overhead patient-centered medical-home practice model in North Carolina.

  4. Using the Overhead Projector as a Light Source for Physics Demonstrations

    ERIC Educational Resources Information Center

    Mak, Se-Yuen

    2006-01-01

    This article illustrates how the overhead projector can be used as a light source in some peculiar ways for physics demonstrations. Five examples are included: (1) Study of chromatic aberration; (2) Making giant Newton's rings; (3) Comparison of the rate of heat absorption by different surfaces; (4) Demonstration of greenhouse effect; and (5)…

  5. Marangoni Flowers and the Evil Eye: Overhead Presentations of Marangoni Flow

    ERIC Educational Resources Information Center

    Mundell, Donald W.

    2009-01-01

    Intermolecular forces and surface tension gradients in solutions lead to remarkable flows, known as Marangoni flows, where liquid flows from a region of low surface tension towards higher surface tension. Details of these flows, not visible to the naked eye, are made visible on an overhead projector owing to variation in the index of refraction.…

  6. Demonstrating Heat Changes on the Overhead Projector with a Projecting Thermometer.

    ERIC Educational Resources Information Center

    Hur, Chinhyu; Solomon, Sally; Wetzel, Christy

    1998-01-01

    Heat changes in a lecture setting can be safely shown on an overhead projector using a simple and inexpensive apparatus. Heat evolution can be observed on a projector with adapted digital thermometers or by illuminating the red fluid in nonmercury thermometers. Describes a setup for doing this as well as a collection of demonstrations involving…

  7. A Dynamic Duo: LCD Overhead Displays and Laptops as Instructional Aids in Introductory Psychology.

    ERIC Educational Resources Information Center

    Ransdell, Sarah

    1989-01-01

    Describes simulation software that was used with an LCD overhead display and laptop computers for large introductory psychology courses. The use of experiment simulators to increase student interest and activity is discussed, hardware is explained, and interaction between students, instructor, and the simulation is described. (14 references) (LRW)

  8. 45. DETAIL OF OVERHEAD SERVICE CRANE (5TON CRANE MANUFACTURED BY ...

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

    45. DETAIL OF OVERHEAD SERVICE CRANE (5-TON CRANE MANUFACTURED BY ARMINGTON CARRIAGE; 3-TON HOIST MANUFACTURED BY WRIGHT HOIST COMPANY) IN VALVEHOUSE FOR NEEDLE VALVE OUTLET WORKS ON GALLERY 2. VIEW TO EAST. - Owyhee Dam, Across Owyhee River, Nyssa, Malheur County, OR

  9. Demonstrating Biological Principles Efficiently and Effectively: The Overhead Is More than Just a Lighted Chalkboard

    ERIC Educational Resources Information Center

    Barden-Gabbei, Laura M.

    2006-01-01

    The overhead projector is an excellent tool for teachers at both the high school and college level. Teachers often use it to display class notes as they monitor students' actions and reactions to the concepts being presented and discussed, to display diagrams and figures too complex to draw on the chalkboard, and more recently to display computer…

  10. Four limb amputations due to electrical burn caused by TV antenna contact with overhead electric cables.

    PubMed

    Celiköz, B; Sengezer, M; Selmanpakoğlu, N

    1997-02-01

    A 22-year-old man who sustained four limb amputations due to an electrical burn caused by contact of a TV receiver antenna with overhead electric cables is presented. The indications for limb amputation and the necessary preventive measures for such injuries are discussed.

  11. 48 CFR 3452.216-71 - Negotiated overhead rates-fixed.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Negotiated overhead rates-fixed. 3452.216-71 Section 3452.216-71 Federal Acquisition Regulations System DEPARTMENT OF EDUCATION ACQUISITION REGULATION CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Texts of Provisions...

  12. Apparatus for positioning modular components on a vertical or overhead surface

    NASA Technical Reports Server (NTRS)

    Haynig, C. C.; Messineo, S. V. (Inventor)

    1976-01-01

    An apparatus is disclosed for holding a plurality of modular components against a surface. A fixture prepositions the components and a vacuum develops a uniform pressure which presses and holds the fixture and objects against a surface. The surface may be curved, vertical, or overhead and since local load concentrations are avoided, fragile ceramic tiles may be installed using the apparatus.

  13. 76 FR 10476 - Special Conditions: Boeing Model 787-8 Airplane; Overhead Crew-Rest Compartment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-25

    ... Crew- Rest Compartment AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final special... will have novel or unusual design features associated with installation of an overhead crew-rest (OCR... Sec. 21.101. Novel or Unusual Design Features Crew-rest compartments have been installed...

  14. 29 CFR 1926.1003 - Overhead protection for operators of agricultural and industrial tractors used in construction.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... REGULATIONS FOR CONSTRUCTION Rollover Protective Structures; Overhead Protection § 1926.1003 Overhead... of a solid material. When grid or mesh is used, the largest permissible opening shall be such that the maximum circle that can be inscribed between the elements of the grid or mesh is 1.5 in. (38...

  15. 77 FR 53914 - Horton Automatics, Inc., a Subsidiary of Overhead Door Corporation Including On-Site Leased...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-04

    ... Employment and Training Administration Horton Automatics, Inc., a Subsidiary of Overhead Door Corporation... Automatics, Inc., a subsidiary of Overhead Door Corporation, including on-site leased workers from Remedy... of automatic sliding, swinging, and revolving doors. The notice was published in the Federal...

  16. Complexes of Peptide Blockers with Kv1.6 Pore Domain: Molecular Modeling and Studies with KcsA-Kv1.6 Channel.

    PubMed

    Nekrasova, O V; Volyntseva, A D; Kudryashova, K S; Novoseletsky, V N; Lyapina, E A; Illarionova, A V; Yakimov, S A; Korolkova, Yu V; Shaitan, K V; Kirpichnikov, M P; Feofanov, A V

    2016-09-17

    Potassium voltage-gated Kv1.6 channel, which is distributed primarily in neurons of central and peripheral nervous systems, is of significant physiological importance. To date, several high-affinity Kv1.6-channel blockers are known, but the lack of selective ones among them hampers the studies of tissue localization and functioning of Kv1.6 channels. Here we present an approach to advanced understanding of interactions of peptide toxin blockers with a Kv1.6 pore. It combines molecular modeling studies and an application of a new bioengineering system based on a KcsA-Kv1.6 hybrid channel for the quantitative fluorescent analysis of blocker-channel interactions. Using this system we demonstrate that peptide toxins agitoxin 2, kaliotoxin1 and OSK1 have similar high affinity to the extracellular vestibule of the K(+)-conducting pore of Kv1.6, hetlaxin is a low-affinity ligand, whereas margatoxin and scyllatoxin do not bind to Kv1.6 pore. Binding of toxins to Kv1.6 pore has considerable inverse dependence on the ionic strength. Model structures of KcsA-Kv1.6 and Kv1.6 complexes with agitoxin 2, kaliotoxin 1 and OSK1 were obtained using homology modeling and molecular dynamics simulation. Interaction interfaces, which are formed by 15-19 toxin residues and 10 channel residues, are described and compared. Specific sites of Kv1.6 pore recognition are identified for targeting of peptide blockers. Analysis of interactions between agitoxin 2 derivatives with point mutations (S7K, S11G, L19S, R31G) and KcsA-Kv1.6 confirms reliability of the calculated complex structure.

  17. The transient outward current in mice lacking the potassium channel gene Kv1.4

    PubMed Central

    London, Barry; Wang, Dao W; Hill, Joseph A; Bennett, Paul B

    1998-01-01

    The transient outward current (Ito) plays a prominent role in the repolarization phase of the cardiac action potential. Several K+ channel genes, including Kv1.4, are expressed in the heart, produce rapidly inactivating currents when heterologously expressed, and may be the molecular basis of Ito.We engineered mice homozygous for a targeted disruption of the K+ channel gene Kv1.4 and compared Ito in wild-type (Kv1.4+/+), heterozygous (Kv1.4+/-) and homozygous ‘knockout’ (Kv1.4−/−) mice. Kv1.4 RNA was truncated in Kv1.4−/− mice and protein expression was absent.Adult myocytes isolated from Kv1.4+/+, Kv1.4+/− and Kv1.4−/− mice had large rapidly inactivating outward currents. The peak current densities at 60 mV (normalized by cellular capacitance, in pA pF−1; means ± s.e.m.) were 53.8 ± 5.3, 45.3 ± 2.2 and 44.4 ± 2.8 in cells from Kv1.4+/+, Kv1.4+/− and Kv1.4−/− mice, respectively (P < 0.02 for Kv1.4+/+ vs. Kv1.4−/−). The steady-state values (800 ms after the voltage clamp step) were 30.9 ± 2.9, 26.9 ± 3.8 and 23.5 ± 2.2, respectively (P < 0.02 for Kv1.4+/+ vs. Kv1.4−/−). The inactivating portion of the current was unchanged in the targeted mice.The voltage dependence and time course of inactivation were not changed by targeted disruption of Kv1.4. The mean best-fitting V½ (membrane potential at 50 % inactivation) values for myocytes from Kv1.4 +/+, Kv1.4+/− and Kv1.4−/− mice were -53.5 ± 3.7, -51.1 ± 2.6 and -54.2 ± 2.4 mV, respectively. The slope factors (k) were -10.1 ± 1.4, -8.8 ± 1.4 and -9.5 ± 1.2 mV, respectively. The fast time constants for development of inactivation at -30 mV were 27.8 ± 2.2, 26.2 ± 5.1 and 19.6 ± 2.1 ms in Kv1.4+/+, Kv1.4+/− and Kv1.4−/− myocytes, respectively. At +30 mV, they were 35.5 ± 2.6, 30.0 ± 2.1 and 28.7 ± 1.6 ms, respectively. The time constants for the rapid phase of recovery from inactivation at -80 mV were 32.5 ± 8.2, 23.3 ± 1.8 and 39.0 ± 3.7 ms, respectively

  18. Differential expression of Kv3.1b and Kv3.2 potassium channel subunits in interneurons of the basolateral amygdala.

    PubMed

    McDonald, A J; Mascagni, F

    2006-01-01

    The expression of Kv3.1 and Kv3.2 voltage-gated potassium channel subunits appears to be critical for high-frequency firing of many neuronal populations. In the cortex these subunits are mainly associated with fast-firing GABAergic interneurons containing parvalbumin or somatostatin. Since the basolateral nuclear complex of the amygdala contains similar interneurons, it is of interest to determine if these potassium channel subunits are expressed in these same interneuronal subpopulations. To investigate this issue, peroxidase and dual-labeling fluorescence immunohistochemistry combined with confocal laser scanning microscopy was used to determine which interneuronal subpopulations in the basolateral nuclear complex of the rat amygdala express Kv3.1b and Kv3.2 subunits. Antibodies to parvalbumin, somatostatin, calretinin, and cholecystokinin were used to label separate subsets of basolateral amygdalar interneurons. Examination of immunoperoxidase preparations suggested that the expression of both channels was restricted to nonpyramidal interneurons in the basolateral amygdala. Somata and proximal dendrites were intensely-stained, and axon terminals arising from presumptive basket cells and chandelier cells were lightly stained. Immunofluorescence observations revealed that parvalbumin+ neurons were the main interneuronal subpopulation expressing the Kv3.1b potassium channel subunit in the basolateral amygdala. More than 92-96% of parvalbumin+ neurons were Kv3.1b+, depending on the nucleus. These parvalbumin+/Kv3.1b+ double-labeled cells constituted 90-99% of all Kv3.1b+ neurons. Parvalbumin+ neurons were also the main interneuronal subpopulation expressing the Kv3.2 potassium channel subunit. More than 67-78% of parvalbumin+ neurons were Kv3.2+, depending on the nucleus. However, these parvalbumin+/Kv3.2+ double-labeled cells constituted only 71-81% of all Kv3.2+ neurons. Most of the remaining neurons with significant levels of the Kv3.2 subunit were somatostatin

  19. Kv3.1b is a novel component of CNS nodes.

    PubMed

    Devaux, Jérôme; Alcaraz, Gisèle; Grinspan, Judith; Bennett, Vann; Joho, Rolf; Crest, Marcel; Scherer, Steven S

    2003-06-01

    We herein demonstrate that Kv3.1b subunits are present at nodes of Ranvier in the CNS of both rats and mice. Kv3.1b colocalizes with voltage-gated Na+ channels in a subset of nodes in the spinal cord, particularly those of large myelinated axons. Kv3.1b is abundantly expressed in the gray matter of the spinal cord, but does not colocalize with Na+ channels in initial segments. In the PNS, few nodes are Kv3.1b-positive. During the development of the CNS, Kv3.1b clustering at nodes occurs later than that of Na+ channels, but precedes the juxtaparanodal clustering of Kv1.2. Moreover, in myelin-deficient rats, which have severe CNS dysmyelination, node-like clusters of Kv3.1b and Na+ channels are observed even in regions devoid of oligodendrocytes. Ankyrin G coimmunoprecipitates Kv3.1b in vivo, indicating that these two proteins may interact in the CNS at nodes. 4-Aminopyridine, a K+ channel blocker, broadened the compound action potential recorded from adult rat optic nerve and spinal cord, but not from the sciatic nerve. These effects were also observed in Kv3.1-deficient mice. In conclusion, Kv3.1b is the first K+ channel subunit to be identified in CNS nodes; but Kv3.1b does not account for the effects of 4-aminopyridine on central myelinated tracts.

  20. Src regulates membrane trafficking of the Kv3.1b channel.

    PubMed

    Bae, Seong Han; Kim, Dong Hyun; Shin, Seok Kyo; Choi, Jin Sung; Park, Kang-Sik

    2014-01-03

    The Kv3.1 channel plays a crucial role in regulating the high-frequency firing properties of neurons. Here, we determined whether Src regulates the subcellular distributions of the Kv3.1b channel. Co-expression of active Src induced a dramatic redistribution of Kv3.1b to the endoplasmic reticulum. Furthermore, co-expression of the Kv3.1b channel with active Src induced a remarkable decrease in the pool of Kv3.1b at the cell surface. Moreover, the co-expression of active Src results in a significant decrease in the peak current densities of the Kv3.1b channel, and a substantial alteration in the voltage dependence of its steady-state inactivation. Taken together, these results indicate that Src kinase may play an important role in regulating membrane trafficking of Kv3.1b channels.

  1. β Subunits Functionally Differentiate Human Kv4.3 Potassium Channel Splice Variants

    PubMed Central

    Abbott, Geoffrey W.

    2017-01-01

    The human ventricular cardiomyocyte transient outward K+ current (Ito) mediates the initial phase of myocyte repolarization and its disruption is implicated in Brugada Syndrome and heart failure (HF). Human cardiac Ito is generated primarily by two Kv4.3 splice variants (Kv4.3L and Kv4.3S, diverging only by a C-terminal, S6-proximal, 19-residue stretch unique to Kv4.3L), which are differentially remodeled in HF, but considered functionally alike at baseline. Kv4.3 is regulated in human heart by β subunits including KChIP2b and KCNEs, but their effects were previously assumed to be Kv4.3 isoform-independent. Here, this assumption was tested experimentally using two-electrode voltage-clamp analysis of human subunits co-expressed in Xenopus laevis oocytes. Unexpectedly, Kv4.3L-KChIP2b channels exhibited up to 8-fold lower current augmentation, 40% slower inactivation, and 5 mV-shifted steady-state inactivation compared to Kv4.3S-KChIP2b. A synthetic peptide mimicking the 19-residue stretch diminished these differences, reinforcing the importance of this segment in mediating Kv4.3 regulation by KChIP2b. KCNE subunits induced further functional divergence, including a 7-fold increase in Kv4.3S-KCNE4-KChIP2b current compared to Kv4.3L-KCNE4-KChIP2b. The discovery of β-subunit-dependent functional divergence in human Kv4.3 splice variants suggests a C-terminal signaling hub is crucial to governing β-subunit effects upon Kv4.3, and demonstrates the potential significance of differential Kv4.3 gene-splicing and β subunit expression in myocyte physiology and pathobiology. PMID:28228734

  2. Regulation of Kv2.1 K+ conductance by cell surface channel density

    PubMed Central

    Fox, Philip D.; Loftus, Rob J.; Tamkun, Michael M.

    2013-01-01

    The Kv2.1 voltage-gated K+ channel is found both freely diffusing over the plasma membrane and concentrated in micron-sized clusters localized to the soma, proximal dendrites and axon initial segment of hippocampal neurons. In transfected HEK cells, Kv2.1 channels within cluster microdomains are non-conducting. Using TIRF microscopy the number of GFP-tagged Kv2.1 channels on the HEK cell surface was compared to K+ channel conductance measured by whole-cell voltage-clamp of the same cell. This approach indicated that as channel density increases non-clustered channels cease conducting. At the highest density observed, only 4% of all channels were conducting. Mutant Kv2.1 channels that fail to cluster also possessed the non-conducting state with 17% conducting K+ at higher surface densities. The non-conducting state was specific to Kv2.1 as Kv1.4 was always conducting regardless of the cell-surface expression level. Anti-Kv2.1 immuno-fluorescence intensity, standardized to Kv2.1 surface density in transfected HEK cells, was used to determine the expression levels of endogenous Kv2.1 in cultured rat hippocampal neurons. Endogenous Kv2.1 levels were compared to the number of conducting channels determined by whole-cell voltage clamp. Only 13 and 27% of the endogenous Kv2.1 was conducting in neurons cultured for 14 and 20 days, respectively. Together these data indicate that the non-conducting state depends primarily on surface density as opposed to cluster location and that this non-conducting state also exists for native Kv2.1 found in cultured hippocampal neurons. This excess of Kv2.1 protein relative to K+ conductance further supports a non-conducting role for Kv2.1 in excitable tissues. PMID:23325261

  3. Neuronal activity and TrkB ligands influence Kv3.1b and Kv3.2 expression in developing cortical interneurons.

    PubMed

    Grabert, J; Wahle, P

    2008-10-15

    Among the GABAergic neocortical interneurons, fast-spiking (FS) basket and chandelier cells are essential mediators for feed-forward inhibition, network synchrony and oscillations. The FS properties are in part mediated by the voltage-gated potassium channels Kv3.1b/3.2 which allow the fast repolarization of the membrane necessary for firing non-adapting action potentials at high frequencies. It has been recently reported that the FS phenotype fails to mature in BDNF knockout mice suggesting a role for neurotrophins. We now describe the role of neuronal activity and neurotrophins for Kv3.1b/3.2 expression using organotypic cultures of rat visual cortex as model system. Chronic activity deprivation from 2 days in vitro (DIV) prevented the postnatal developmental increase of Kv3.2, but not Kv3.1b mRNA expression. However, chronic activity deprivation failed to alter Kv3.1b and marginally delayed Kv3.2 protein expression. Activity deprivation by glutamate receptor blockade from 10 to 20 DIV reduced both mRNAs, whereas deprivation with tetrodotoxin (TTX) reduced both mRNAs and the Kv3.2 protein. Thalamic and cortical afferents in cocultures failed to alter the expression. BDNF and NT4 supplemented from 2 DIV onwards increased the expression of Kv3.1b, but not Kv3.2 mRNA in young cultures. Only NT4 increased the expression of both mRNAs later in development. Kv3 protein levels were not changed by exogenous tropomyosin-related kinase B (TrkB) ligands, but the levels decreased upon inhibiting the MAPK signaling suggesting a role for endogenous factors and in particular MEK2 signaling for translation. The results show that Kv3.1b/3.2 expression is differentially controlled by neuronal activity and neurotrophic factors.

  4. 75 FR 9573 - Minnkota Power Cooperative, Inc: Bemidji-Grand Rapids 230kV Transmission Project

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-03

    ... Rural Utilities Service Minnkota Power Cooperative, Inc: Bemidji-Grand Rapids 230kV Transmission Project... Minnkota Power Cooperative, Inc (Minnkota) for the construction of a 230 kilovolt (kV) kV transmission line... Minnesota Power, proposes to construct and operate a 230 kV transmission line between the Wilton...

  5. State-dependent inactivation of the Kv3 potassium channel.

    PubMed Central

    Marom, S; Levitan, I B

    1994-01-01

    Inactivation of Kv3 (Kv1.3) delayed rectifier potassium channels was studied in the Xenopus oocyte expression system. These channels inactivate slowly during a long depolarizing pulse. In addition, inactivation accumulates in response to a series of short depolarizing pulses (cumulative inactivation), although no significant inactivation occurs within each short pulse. The extent of cumulative inactivation does not depend on the voltage during the depolarizing pulse, but it does vary in a biphasic manner as a function of the interpulse duration. Furthermore, the rate of cumulative inactivation is influenced by changing the rate of deactivation. These data are consistent with a model in which Kv3 channel inactivation is a state-dependent and voltage-independent process. Macroscopic and single channel experiments indicate that inactivation can occur from a closed (silent) state before channel opening. That is, channels need not open to inactivate. The transition that leads to the inactivated state from the silent state is, in fact, severalfold faster then the observed inactivation of current during long depolarizing pulses. Long pulse-induced inactivation appears to be slow, because its rate is limited by the probability that channels are in the open state, rather than in the silent state from which they can inactivate. External potassium and external calcium ions alter the rates of cumulative and long pulse-induced inactivation, suggesting that antagonistic potassium and calcium binding steps are involved in the normal gating of the channel. PMID:7948675

  6. A low overhead load balancing router for network-on-chip

    NASA Astrophysics Data System (ADS)

    Xiaofeng, Zhou; Lu, Liu; Zhangming, Zhu; Duan, Zhou

    2016-11-01

    The design of a router in a network-on-chip (NoC) system has an important impact on some performance criteria. In this paper, we propose a low overhead load balancing router (LOLBR) for 2D mesh NoC to enhance routing performance criteria with low hardware overhead. The proposed LOLBR employs a balance toggle identifier to control the initial routing direction of X or Y for flit injection. The simplified demultiplexers and multiplexers are used to handle output ports allocation and contention, which provide a guarantee of deadlock avoidance. Simulation results show that the proposed LOLBR yields an improvement of routing performance over the reported routing schemes in average packet latency by 26.5%. The layout area and power consumption of the network compared with the reported routing schemes are 15.3% and 11.6% less respectively. Project supported by the National Natural Science Foundation of China (Nos. 61474087, 61322405, 61376039).

  7. 3-D Object Recognition Using Combined Overhead And Robot Eye-In-Hand Vision System

    NASA Astrophysics Data System (ADS)

    Luc, Ren C.; Lin, Min-Hsiung

    1987-10-01

    A new approach for recognizing 3-D objects using a combined overhead and eye-in-hand vision system is presented. A novel eye-in-hand vision system using a fiber-optic image array is described. The significance of this approach is the fast and accurate recognition of 3-D object information compared to traditional stereo image processing. For the recognition of 3-D objects, the over-head vision system will take 2-D top view image and the eye-in-hand vision system will take side view images orthogonal to the top view image plane. We have developed and demonstrated a unique approach to integrate this 2-D information into a 3-D representation based on a new approach called "3-D Volumetric Descrip-tion from 2-D Orthogonal Projections". The Unimate PUMA 560 and TRAPIX 5500 real-time image processor have been used to test the success of the entire system.

  8. A Hybrid Method for Evaluating of Lightning Performance of Overhead Lines based on Monte Carlo Procedure

    NASA Astrophysics Data System (ADS)

    Shariatinasab, Reza; Tadayon, Pooya; Ametani, Akihiro

    2016-07-01

    This paper proposes a hybrid method for calculating lightning performance of overhead lines caused by direct strokes by combining Lattice diagram together with the Monte Carlo method. In order to go through this, firstly, the proper analytical relations for overvoltages calculation are established based on Lattice diagram. Then, the Monte Carlo procedure is applied to the obtained analytical relations. The aim of the presented method that will be called `ML method' is simply estimation of the lightning performance of the overhead lines and performing the risk analysis of power apparatus with retaining the acceptable accuracy. To confirm the accuracy, the calculated results of the presented ML method are compared with those calculated by the EMTP/ATP simulation.

  9. A fuzzy-logic antiswing controller for three-dimensional overhead cranes.

    PubMed

    Cho, Sung-Kun; Lee, Ho-Hoon

    2002-04-01

    In this paper, a new fuzzy antiswing control scheme is proposed for a three-dimensional overhead crane. The proposed control consists of a position servo control and a fuzzy-logic control. The position servo control is used to control crane position and rope length, and the fuzzy-logic control is used to suppress load swing. The proposed control guarantees not only prompt suppression of load swing but also accurate control of crane position and rope length for simultaneous travel, traverse, and hoisting motions of the crane. Furthermore, the proposed control provides practical gain tuning criteria for easy application. The effectiveness of the proposed control is shown by experiments with a three-dimensional prototype overhead crane.

  10. GAMMA FACILITY, TRA611, INTERIOR. WITH HELP OF OVERHEAD CHAIN AND ...

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

    GAMMA FACILITY, TRA-611, INTERIOR. WITH HELP OF OVERHEAD CHAIN AND HOOK, SCIENTIST GUIDES METAL CONTAINER (HOLDING POTATOES, IN THIS CASE) INTO RECEIVING "COLUMN" IN THE GAMMA CANAL. NOTE OTHER COLUMNS AT RIGHT AND LEFT WALLS OF CANAL. NEAR BOTTOM OF CANAL, SPENT MTR FUEL WILL IRRADIATE POTATOES. INL NEGATIVE NO. 56-439. R.G. Larsen, Photographer, 2/8/1956 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  11. Characterization Results for the March 2016 H-Tank Farm 2H Evaporator Overhead Samples

    SciTech Connect

    Nicholson, J. C.

    2016-05-09

    This report contains the radioanalytical results of the 2H evaporator overhead sample received at SRNL on March 16, 2016. Specifically, concentrations of 137Cs, 90Sr, and 129I are reported and compared to the corresponding Waste Acceptance Criteria (WAC) limits of the Effluent Treatment Project (ETP) Waste Water Collection Tank (WWCT) (rev. 6). All of the radionuclide concentrations in the sample were found to be in compliance with the ETP WAC limits.

  12. Estimation of the maximal voltage induced on an overhead line due to the nearby lightning

    SciTech Connect

    Jankov, V.

    1997-01-01

    Determination of the maximal voltages induced on the overhead power lines by nearby lightning stroke is a complex problem. The scope of this paper is to recognize the parameters that affect the maximal voltages and to present an equation for their estimation. This equation gives an opportunity to calculate the maximal voltage with the reasonable accuracy avoiding complex electromagnetic field calculus. It may be very useful in the estimation of flashover and outage rates due to the nearby strokes.

  13. Characterization Results For The 2013 HTF 3H Evaporator Overhead Samples

    SciTech Connect

    Washington, A. L. II

    2013-12-04

    This report tabulates the radiochemical analysis of the 3H evaporator overhead sample for {sup 137}Cs, {sup 90}Sr, and {sup 129}I to meet the requirements in the Effluent Treatment Project (ETP) Waste Acceptance Criteria (WAC) (rev. 6). This report identifies the sample receipt date, preparation method, and analysis performed in the accumulation of the listed values. All data was found to be within the ETP WAC (rev. 6) specification for the Waste Water Collection Tanks (WWCT).

  14. The effects of overhead transparency design on retention, recall, and application of data analysis content.

    PubMed

    Van Hoozer, H; Brink, P J; Oppliger, R

    1989-04-01

    This experimental study tested the effects of overhead transparency design in conjunction with live lecture on retention, recall, and application of data analysis content over three occasions using a Solomon Four-Group, pretest-posttest design. Pretested subjects showed significant (p less than .001) gains in test scores from pre to posttest. No significant differences were found in pretest scores between control and experimental treatment groups or among the posttest scores of either the experimental or control groups.

  15. Characterization results for the October 2015-Tank for farm 3H evaporator overhead examples

    SciTech Connect

    Nicholson, J. C.

    2016-01-28

    This report contains the radioanalytical results of the 3H evaporator overhead sample received at SRNL on October 13, 2015. Specifically, concentrations of 137Cs, 90Sr, and 129I are reported and compared to the corresponding Waste Acceptance Criteria (WAC) limits of the Effluent Treatment Project (ETP) Waste Water Collection Tank (WWCT) (rev. 6). All of the radionuclide concentrations in the sample were found to be in compliance with the ETP WAC limits.

  16. Allocating physicians' overhead costs to services: an econometric/accounting-activity based-approach.

    PubMed

    Peden, Al; Baker, Judith J

    2002-01-01

    Using the optimizing properties of econometric analysis, this study analyzes how physician overhead costs (OC) can be allocated to multiple activities to maximize precision in reimbursing the costs of services. Drawing on work by Leibenstein and Friedman, the analysis also shows that allocating OC to multiple activities unbiased by revenue requires controlling for revenue when making the estimates. Further econometric analysis shows that it is possible to save about 10 percent of OC by paying only for those that are necessary.

  17. A Formula for Use in Unabsorbed Overhead Claims in Government Contracts.

    DTIC Science & Technology

    1986-09-01

    31868 Contract 2 Direct Labor $ 7360 Overhead @ 178.57% 13143 Subtotal $20503 Profit--10% 2050 Total $22553 Replacement Work Direct Labor $ 360...Work Days (@ $40 per day) 9 days 1Average Replacement Work Direct Labor $ 24 (for the 15 day delay period) Average Direct Labor--Delay Period $ 88...Replacement Work Days (@ $40 per day) 9 days Average Replacement Work Direct Labor $ 24 (for the 15 day delay period) U Average Direct Labor--Delay Period $ 88

  18. STS-30 aft flight deck onboard view of overhead window, Earth limb, cow photo

    NASA Technical Reports Server (NTRS)

    1989-01-01

    Since the beginning of manned space travel, astronauts have taken onboard with them items of person sentiment. During STS-30 onboard Atlantis, Orbiter Vehicle (OV) 104, Mission Specialist Mark C. Lee brought along a photograph of a cow. The photo testifies to his background as one reared on a Wisconsin farm and is displayed on aft flight deck alongside an overhead window. Outside the window, some 160 nautical miles away, is the cloud-covered Earth surface.

  19. Extracellular chloride regulation of Kv2.1, contributor to the major outward Kv current in mammalian outer hair cells

    PubMed Central

    Li, Xiantao; Surguchev, Alexei; Bian, Shumin; Navaratnam, Dhasakumar

    2012-01-01

    Outer hair cells (OHC) function as both receptors and effectors in providing a boost to auditory reception. Amplification is driven by the motor protein prestin, which is under anionic control. Interestingly, we now find that the major, 4-AP-sensitive, outward K+ current of the OHC (IK) is also sensitive to Cl−, although, in contrast to prestin, extracellularly. IK is inhibited by reducing extracellular Cl− levels, with a linear dependence of 0.4%/mM. Other voltage-dependent K+ (Kv) channel conductances in supporting cells, such as Hensen and Deiters' cells, are not affected by reduced extracellular Cl−. To elucidate the molecular basis of this Cl−-sensitive IK, we looked at potential molecular candidates based on Cl− sensitivity and/or similarities in kinetics. For IK, we identified three different Ca2+-independent components of IK based on the time constant of inactivation: a fast, transient outward current, a rapidly activating, slowly inactivating current (Ik1), and a slowly inactivating current (Ik2). Extracellular Cl− differentially affects these components. Because the inactivation time constants of Ik1 and Ik2 are similar to those of Kv1.5 and Kv2.1, we transiently transfected these constructs into CHO cells and found that low extracellular Cl− inhibited both channels with linear current reductions of 0.38%/mM and 0.49%/mM, respectively. We also tested heterologously expressed Slick and Slack conductances, two intracellularly Cl−-sensitive K+ channels, but found no extracellular Cl− sensitivity. The Cl− sensitivity of Kv2.1 and its robust expression within OHCs verified by single-cell RT-PCR indicate that these channels underlie the OHC's extracellular Cl− sensitivity. PMID:21940671

  20. Unconventional EGF-induced ERK1/2-mediated Kv1.3 endocytosis.

    PubMed

    Martínez-Mármol, Ramón; Comes, Núria; Styrczewska, Katarzyna; Pérez-Verdaguer, Mireia; Vicente, Rubén; Pujadas, Lluís; Soriano, Eduardo; Sorkin, Alexander; Felipe, Antonio

    2016-04-01

    The potassium channel Kv1.3 plays roles in immunity, neuronal development and sensory discrimination. Regulation of Kv1.3 by kinase signaling has been studied. In this context, EGF binds to specific receptors (EGFR) and triggers tyrosine kinase-dependent signaling, which down-regulates Kv1.3 currents. We show that Kv1.3 undergoes EGF-dependent endocytosis. This EGF-mediated mechanism is relevant because is involved in adult neural stem cell fate determination. We demonstrated that changes in Kv1.3 subcellular distribution upon EGFR activation were due to Kv1.3 clathrin-dependent endocytosis, which targets the Kv1.3 channels to the lysosomal degradative pathway. Interestingly, our results further revealed that relevant tyrosines and other interacting motifs, such as PDZ and SH3 domains, were not involved in the EGF-dependent Kv1.3 internalization. However, a new, and yet undescribed mechanism, of ERK1/2-mediated threonine phosphorylation is crucial for the EGF-mediated Kv1.3 endocytosis. Our results demonstrate that EGF triggers the down-regulation of Kv1.3 activity and its expression at the cell surface, which is important for the development and migration of adult neural progenitors.

  1. Developmental Expression of Kv Potassium Channels at the Axon Initial Segment of Cultured Hippocampal Neurons

    PubMed Central

    Sánchez-Ponce, Diana; DeFelipe, Javier; Garrido, Juan José; Muñoz, Alberto

    2012-01-01

    Axonal outgrowth and the formation of the axon initial segment (AIS) are early events in the acquisition of neuronal polarity. The AIS is characterized by a high concentration of voltage-dependent sodium and potassium channels. However, the specific ion channel subunits present and their precise localization in this axonal subdomain vary both during development and among the types of neurons, probably determining their firing characteristics in response to stimulation. Here, we characterize the developmental expression of different subfamilies of voltage-gated potassium channels in the AISs of cultured mouse hippocampal neurons, including subunits Kv1.2, Kv2.2 and Kv7.2. In contrast to the early appearance of voltage-gated sodium channels and the Kv7.2 subunit at the AIS, Kv1.2 and Kv2.2 subunits were tethered at the AIS only after 10 days in vitro. Interestingly, we observed different patterns of Kv1.2 and Kv2.2 subunit expression, with each confined to distinct neuronal populations. The accumulation of Kv1.2 and Kv2.2 subunits at the AIS was dependent on ankyrin G tethering, it was not affected by disruption of the actin cytoskeleton and it was resistant to detergent extraction, as described previously for other AIS proteins. This distribution of potassium channels in the AIS further emphasizes the heterogeneity of this structure in different neuronal populations, as proposed previously, and suggests corresponding differences in action potential regulation. PMID:23119056

  2. Disruption of Kv1.3 Channel Forward Vesicular Trafficking by Hypoxia in Human T Lymphocytes*

    PubMed Central

    Chimote, Ameet A.; Kuras, Zerrin; Conforti, Laura

    2012-01-01

    Hypoxia in solid tumors contributes to decreased immunosurveillance via down-regulation of Kv1.3 channels in T lymphocytes and associated T cell function inhibition. However, the mechanisms responsible for Kv1.3 down-regulation are not understood. We hypothesized that chronic hypoxia reduces Kv1.3 surface expression via alterations in membrane trafficking. Chronic hypoxia decreased Kv1.3 surface expression and current density in Jurkat T cells. Inhibition of either protein synthesis or degradation and endocytosis did not prevent this effect. Instead, blockade of clathrin-coated vesicle formation and forward trafficking prevented the Kv1.3 surface expression decrease in hypoxia. Confocal microscopy revealed an increased retention of Kv1.3 in the trans-Golgi during hypoxia. Expression of adaptor protein-1 (AP1), responsible for clathrin-coated vesicle formation at the trans-Golgi, was selectively down-regulated by hypoxia. Furthermore, AP1 down-regulation increased Kv1.3 retention in the trans-Golgi and reduced Kv1.3 currents. Our results indicate that hypoxia disrupts AP1/clathrin-mediated forward trafficking of Kv1.3 from the trans-Golgi to the plasma membrane thus contributing to decreased Kv1.3 surface expression in T lymphocytes. PMID:22134923

  3. Dromedary immune response and specific Kv2.1 antibody generation using a specific immunization approach.

    PubMed

    Hassiki, Rym; Labro, Alain J; Benlasfar, Zakaria; Vincke, Cécile; Somia, Mahmoud; El Ayeb, Mohamed; Muyldermans, Serge; Snyders, Dirk J; Bouhaouala-Zahar, Balkiss

    2016-12-01

    Voltage-gated potassium (Kv) channels form cells repolarizing power and are commonly expressed in excitable cells. In non-excitable cells, Kv channels such as Kv2.1 are involved in cell differentiation and growth. Due to the involvement of Kv2.1 in several physiological processes, these channels are promising therapeutic targets. To develop Kv2.1 specific antibody-based channel modulators, we applied a novel approach and immunized a dromedary with heterologous Ltk- cells that overexpress the mouse Kv2.1 channel instead of immunizing with channel protein fragments. The advantage of this approach is that the channel is presented in its native tetrameric configuration. Using a Cell-ELISA, we demonstrated the ability of the immune serum to detect Kv2.1 channels on the surface of cells that express the channel. Then, using a Patch Clamp electrophysiology assay we explored the capability of the dromedary serum in modulating Kv2.1 currents. Cells that were incubated for 3h with serum taken at Day 51 from the start of the immunization displayed a statistically significant 2-fold reduction in current density compared to control conditions as well as cells incubated with serum from Day 0. Here we show that an immunization approach with cells overexpressing the Kv2.1 channel yields immune serum with Kv2.1 specific antibodies.

  4. Properties and expression of Kv3 channels in cerebellar Purkinje cells.

    PubMed

    Sacco, Tiziana; De Luca, Annarita; Tempia, Filippo

    2006-10-01

    In cerebellar Purkinje cells, Kv3 potassium channels are indispensable for firing at high frequencies. In Purkinje cells from young mice (P4-P7), Kv3 currents, recorded in whole-cell in slices, activated at -30 mV, with rapid activation and deactivation kinetics, and they were partially blocked by blood depressing substance-I (BDS-I, 1 microM). At positive potentials, Kv3 currents were slowly but completely inactivating, while the recovery from inactivation was about eightfold slower, suggesting that a previous firing activity or a small change of the resting potential could in principle accumulate inactivated Kv3 channels, thereby finely tuning Kv3 current availability for subsequent action potentials. Single-cell RT-PCR analysis showed the expression by all Purkinje cells (n=10 for each subunit) of Kv3.1, Kv3.3 and Kv3.4 mRNA, while Kv3.2 was not expressed. These results add to the framework for interpreting the physiological function and the molecular determinants of Kv3 currents in cerebellar Purkinje cells.

  5. The Role of KV7.3 in Regulating Osteoblast Maturation and Mineralization

    PubMed Central

    Yang, Ji Eun; Song, Min Seok; Shen, Yiming; Ryu, Pan Dong; Lee, So Yeong

    2016-01-01

    KCNQ (KV7) channels are voltage-gated potassium (KV) channels, and the function of KV7 channels in muscles, neurons, and sensory cells is well established. We confirmed that overall blockade of KV channels with tetraethylammonium augmented the mineralization of bone-marrow-derived human mesenchymal stem cells during osteogenic differentiation, and we determined that KV7.3 was expressed in MG-63 and Saos-2 cells at the mRNA and protein levels. In addition, functional KV7 currents were detected in MG-63 cells. Inhibition of KV7.3 by linopirdine or XE991 increased the matrix mineralization during osteoblast differentiation. This was confirmed by alkaline phosphatase, osteocalcin, and osterix in MG-63 cells, whereas the expression of Runx2 showed no significant change. The extracellular glutamate secreted by osteoblasts was also measured to investigate its effect on MG-63 osteoblast differentiation. Blockade of KV7.3 promoted the release of glutamate via the phosphorylation of extracellular signal-regulated kinase 1/2-mediated upregulation of synapsin, and induced the deposition of type 1 collagen. However, activation of KV7.3 by flupirtine did not produce notable changes in matrix mineralization during osteoblast differentiation. These results suggest that KV7.3 could be a novel regulator in osteoblast differentiation. PMID:26999128

  6. The Importance of Immunohistochemical Analyses in Evaluating the Phenotype of Kv Channel Knockout Mice

    PubMed Central

    Menegola, Milena; Clark, Eliana; Trimmer, James S.

    2012-01-01

    Summary To gain insights into the phenotype of Kv1.1 and Kv4.2 knockout mice, we used immunohistochemistry to analyze expression of component principal or α subunits and auxiliary subunits of neuronal Kv channels in knockout mouse brains. Genetic ablation of the Kv1.1 α subunit did not result in compensatory changes in the expression levels or subcellular distribution of related ion channel subunits in hippocampal medial perforant path and mossy fiber nerve terminals, where high levels of Kv1.1 are normally expressed. Genetic ablation of the Kv4.2 α subunit did not result in altered neuronal cytoarchitecture of the hippocampus. While Kv4.2 knockout mice did not exhibit compensatory changes in the expression levels or subcellular distribution of the related Kv4.3 α subunit, we found dramatic decreases in the cellular and subcellular expression of specific KChIPs that reflected their degree of association and colocalization with Kv4.2 in wild-type mouse and rat brains. These studies highlight the insights that can be gained by performing detailed immunohistochemical analyses of Kv channel knockout mouse brains. PMID:22612819

  7. An engineered scorpion toxin analogue with improved Kv1.3 selectivity displays reduced conformational flexibility

    PubMed Central

    Bartok, Adam; Fehér, Krisztina; Bodor, Andrea; Rákosi, Kinga; Tóth, Gábor K.; Kövér, Katalin E.; Panyi, Gyorgy; Varga, Zoltan

    2015-01-01

    The voltage-gated Kv1.3 K+ channel plays a key role in the activation of T lymphocytes. Kv1.3 blockers selectively suppress immune responses mediated by effector memory T cells, which indicates the great potential of selective Kv1.3 inhibitors in the therapy of certain autoimmune diseases. Anuroctoxin (AnTx), a 35-amino-acid scorpion toxin is a high affinity blocker of Kv1.3, but also blocks Kv1.2 with similar potency. We designed and produced three AnTx variants: ([F32T]-AnTx, [N17A]-AnTx, [N17A/F32T]-AnTx) using solid-phase synthesis with the goal of improving the selectivity of the toxin for Kv1.3 over Kv1.2 while keeping the high affinity for Kv1.3. We used the patch-clamp technique to determine the blocking potency of the synthetic toxins on hKv1.3, mKv1.1, hKv1.2 and hKCa3.1 channels. Of the three variants [N17A/F32T]-AnTx maintained the high affinity of the natural peptide for Kv1.3 but became more than 16000-fold selective over Kv1.2. NMR data and molecular dynamics simulations suggest that the more rigid structure with restricted conformational space of the double substituted toxin compared to the flexible wild-type one is an important determinant of toxin selectivity. Our results provide the foundation for the possibility of the production and future therapeutic application of additional, even more selective toxins targeting various ion channels. PMID:26689143

  8. Comparison of charged nanoparticle concentrations near busy roads and overhead high-voltage power lines.

    PubMed

    Jayaratne, E R; Ling, X; Morawska, L

    2015-09-01

    Overhead high-voltage power lines are known sources of corona ions. These ions rapidly attach to aerosols to form charged particles in the environment. Although the effect of ions and charged particles on human health is largely unknown, much attention has focused on the increasing exposure as a result of the expanding power network in urban residential areas. However, it is not widely known that a large number of charged particles in urban environments originate from motor vehicle emissions. In this study, for the first time, we compare the concentrations of charged nanoparticles near busy roads and overhead power lines. We show that large concentrations of both positive and negative charged nanoparticles are present near busy roadways and that these concentrations commonly exceed those under high-voltage power lines. We estimate that the concentration of charged nanoparticles found near two freeways carrying around 120 vehicles per minute exceeded the corresponding maximum concentrations under two corona-emitting overhead power lines by as much as a factor of 5. The difference was most pronounced when a significant fraction of traffic consisted of heavy-duty diesel vehicles which typically have high particle and charge emission rates.

  9. A Novel Transient Fault Current Sensor Based on the PCB Rogowski Coil for Overhead Transmission Lines.

    PubMed

    Liu, Yadong; Xie, Xiaolei; Hu, Yue; Qian, Yong; Sheng, Gehao; Jiang, Xiuchen

    2016-05-21

    The accurate detection of high-frequency transient fault currents in overhead transmission lines is the basis of malfunction detection and diagnosis. This paper proposes a novel differential winding printed circuit board (PCB) Rogowski coil for the detection of transient fault currents in overhead transmission lines. The interference mechanism of the sensor surrounding the overhead transmission line is analyzed and the guideline for the interference elimination is obtained, and then a differential winding printed circuit board (PCB) Rogowski coil is proposed, where the branch and return line of the PCB coil were designed to be strictly symmetrical by using a joining structure of two semi-rings and collinear twisted pair differential windings in each semi-ring. A serial test is conducted, including the frequency response, linearity, and anti-interference performance as well as a comparison with commercial sensors. Results show that a PCB Rogowski coil has good linearity and resistance to various external magnetic field interferences, thus enabling it to be widely applied in fault-current-collecting devices.

  10. A Novel Transient Fault Current Sensor Based on the PCB Rogowski Coil for Overhead Transmission Lines

    PubMed Central

    Liu, Yadong; Xie, Xiaolei; Hu, Yue; Qian, Yong; Sheng, Gehao; Jiang, Xiuchen

    2016-01-01

    The accurate detection of high-frequency transient fault currents in overhead transmission lines is the basis of malfunction detection and diagnosis. This paper proposes a novel differential winding printed circuit board (PCB) Rogowski coil for the detection of transient fault currents in overhead transmission lines. The interference mechanism of the sensor surrounding the overhead transmission line is analyzed and the guideline for the interference elimination is obtained, and then a differential winding printed circuit board (PCB) Rogowski coil is proposed, where the branch and return line of the PCB coil were designed to be strictly symmetrical by using a joining structure of two semi-rings and collinear twisted pair differential windings in each semi-ring. A serial test is conducted, including the frequency response, linearity, and anti-interference performance as well as a comparison with commercial sensors. Results show that a PCB Rogowski coil has good linearity and resistance to various external magnetic field interferences, thus enabling it to be widely applied in fault-current-collecting devices. PMID:27213402

  11. Uptake and Accumulation of Pharmaceuticals in Lettuce Under Surface and Overhead Irrigations

    NASA Astrophysics Data System (ADS)

    Bhalsod, G.; Chuang, Y. H.; Jeon, S.; Gui, W.; Li, H.; Guber, A.; Zhang, W.

    2015-12-01

    Pharmaceuticals and personal care products are being widely detected in wastewater and surface waters. As fresh water becomes scarcer, interests in using reclaimed water for crop irrigation is intensified. Since reclaimed waters often carry trace levels of pharmaceuticals, accumulation of pharmaceuticals in food crops could increase the risk of human exposure. This study aims to investigate uptake and accumulations of pharmaceuticals in greenhouse-grown lettuce under contrasting irrigation practices (i.e., overhead and surface irrigations). Lettuce was irrigated with water spiked with 11 commonly used pharmaceuticals (acetaminophen, caffeine, carbamazepine, sulfadiazine, sulfamethoxazole, carbadox, trimethoprim, lincomycin hydrochloride, oxytetracycline hydrochloride, monensin sodium, and tylosin). Weekly sampling of lettuce roots, shoots, and soils were continued for 5 weeks, and the samples were freeze dried, extracted for pharmaceuticals and analyzed by LC-MS/MS. Preliminary results indicate that higher concentrations of pharmaceuticals were found in overhead irrigated lettuce compared to surface irrigated lettuce. For carbamezapine, sulfadiazine, trimethoprim, oxytetracycline, and monensin sodium, their concentrations generally increased in lettuce shoots in the overhead treatment over time. However, acetaminophen was found at higher concentrations in both shoots and roots, indicating that acetaminophen can be easily transported in the plant system. This study provides insight on developing better strategies for using reclaimed water for crop irrigations, while minimizing the potential risks of pharmaceutical contamination of vegetables.

  12. The Quantitative Overhead Analysis for Effective Task Migration in Biosensor Networks

    PubMed Central

    Kim, Tae-Kyung; Eom, Jung-Ho; Chung, Tai-Myoung

    2013-01-01

    We present a quantitative overhead analysis for effective task migration in biosensor networks. A biosensor network is the key technology which can automatically provide accurate and specific parameters of a human in real time. Biosensor nodes are typically very small devices, so the use of computing resources is restricted. Due to the limitation of nodes, the biosensor network is vulnerable to an external attack against a system for exhausting system availability. Since biosensor nodes generally deal with sensitive and privacy data, their malfunction can bring unexpected damage to system. Therefore, we have to use a task migration process to avoid the malfunction of particular biosensor nodes. Also, it is essential to accurately analyze overhead to apply a proper migration process. In this paper, we calculated task processing time of nodes to analyze system overhead and compared the task processing time applied to a migration process and a general method. We focused on a cluster ratio and different processing time between biosensor nodes in our simulation environment. The results of performance evaluation show that task execution time is greatly influenced by a cluster ratio and different processing time of biosensor nodes. In the results, the proposed algorithm reduces total task execution time in a migration process. PMID:24187668

  13. Developmental changes in the expression of calbindin and potassium-channel subunits Kv3.1b and Kv3.2 in mouse Renshaw cells.

    PubMed

    Song, Z-M; Hu, J; Rudy, B; Redman, S J

    2006-05-12

    One class of spinal interneurons, the Renshaw cells, is able to discharge at very high frequencies in adult mammals. Neuronal firing at such high frequencies requires voltage-gated potassium channels to rapidly repolarize the membrane potential after each action potential. We sought to establish the pattern of expression of calbindin and potassium channels with Kv3.1b and Kv3.2 subunits in Renshaw cells at different developmental stages of postnatal mice. The pattern of expression of calbindin changed dramatically during early postnatal development. An adult pattern of calbindin reactive neurons started to emerge from postnatal day 10 to postnatal day 14, with cells in laminae I and II of superficial dorsal horn and the ventral lamina VII. Renshaw cells were identified immunohistochemically by their expression of calbindin and their location in the ventral horn of the spinal cord. Western blot results of the lumbar spinal cord showed that Kv3.1b expression became faintly evident from postnatal day 10, reached a maximum at postnatal day 21 and was maintained through postnatal day 49. Double labeling results showed that all Renshaw cells expressed Kv3.1b weakly from postnatal day 14, and strongly at postnatal day 21. Western blot results showed that Kv3.2 expression became detectable in the lumbar cord from postnatal day 12, and increased steadily until reaching an adult level at postnatal day 28. In contrast to the Kv3.1b results, Kv3.2 was not expressed in Renshaw cells, although some neurons located at laminae VIII and VI expressed Kv3.2. We conclude that Renshaw cells express Kv3.1b but not Kv3.2 from postnatal day 14.

  14. Acromiohumeral Distance and 3-Dimensional Scapular Position Change After Overhead Muscle Fatigue

    PubMed Central

    Maenhout, Annelies; Dhooge, Famke; Van Herzeele, Maarten; Palmans, Tanneke; Cools, Ann

    2015-01-01

    Context: Muscle fatigue due to repetitive and prolonged overhead sports activity is considered an important factor contributing to impingement-related rotator cuff pathologic conditions in overhead athletes. The evidence on scapular and glenohumeral kinematic changes after fatigue is contradicting and prohibits conclusions about how shoulder muscle fatigue affects acromiohumeral distance. Objective: To investigate the effect of a fatigue protocol resembling overhead sports activity on acromiohumeral distance and 3-dimensional scapular position in overhead athletes. Design: Cross-sectional study. Setting: Institutional laboratory. Patients or Other Participants: A total of 29 healthy recreational overhead athletes (14 men, 15 women; age = 22.23 ± 2.82 years, height = 178.3 ± 7.8 cm, mass = 71.6 ± 9.5 kg). Intervention(s) The athletes were tested before and after a shoulder muscle-fatiguing protocol. Main Outcome Measure(s) Acromiohumeral distance was measured using ultrasound, and scapular position was determined with an electromagnetic motion-tracking system. Both measurements were performed at 3 elevation positions (0°, 45°, and 60° of abduction). We used a 3-factor mixed model for data analysis. Results: After fatigue, the acromiohumeral distance increased when the upper extremity was actively positioned at 45° (Δ = 0.78 ± 0.24 mm, P = .002) or 60° (Δ = 0.58 ± 0.23 mm, P = .02) of abduction. Scapular position changed after fatigue to a more externally rotated position at 45° (Δ = 4.97° ± 1.13°, P < .001) and 60° (Δ = 4.61° ± 1.90°, P = .001) of abduction, a more upwardly rotated position at 45° (Δ = 6.10° ± 1.30°, P < .001) and 60° (Δ = 7.20° ± 1.65°, P < .001) of abduction, and a more posteriorly tilted position at 0°, 45°, and 60° of abduction (Δ = 1.98° ± 0.41°, P < .001). Conclusions: After a fatiguing protocol, we found changes in acromiohumeral distance and scapular position that corresponded with an impingement

  15. Kv3.1/Kv3.2 channel positive modulators enable faster activating kinetics and increase firing frequency in fast-spiking GABAergic interneurons.

    PubMed

    Boddum, Kim; Hougaard, Charlotte; Xiao-Ying Lin, Julie; von Schoubye, Nadia Lybøl; Jensen, Henrik Sindal; Grunnet, Morten; Jespersen, Thomas

    2017-02-24

    Due to their fast kinetic properties, Kv3.1 voltage gated potassium channels are important in setting and controlling firing frequency in neurons and pivotal in generating high frequency firing of interneurons. Pharmacological activation of Kv3.1 channels may possess therapeutic potential for treatment of epilepsy, hearing disorders, schizophrenia and cognitive impairments. Here we thoroughly investigate the selectivity and positive modulation of the two small molecules, EX15 and RE01, on Kv3 channels. Selectivity studies, conducted in Xenopus laevis oocytes confirmed a positive modulatory effect of the two compounds on Kv3.1 and to a minor extent on Kv3.2 channels. RE01 had no effect on the Kv3.3 and Kv3.4 channels, whereas EX15 had an inhibitory impact on the Kv3.4 mediated current. Voltage-clamp experiments in monoclonal hKv3.1b/HEK293 cells (34 °C) revealed that the two compounds indeed induced larger currents and faster activation kinetics. They also decrease the speed of deactivation and shifted the voltage dependence of activation, to a more negative activation threshold. Application of action potential clamping and repetitive stimulation protocols of hKv3.1b expressing HEK293 cells revealed that EX15 and RE01 significantly increased peak amplitude, half width and decay time of Kv3.1 mediated currents, even during high-frequency action potential clamping (250 Hz). In rat hippocampal slices, EX15 and RE01 increased neuronal excitability in fast-spiking interneurons in dentate gyrus. Action potential frequency was prominently increased at minor depolarizing steps, whereas more marginal effects of EX15 and RE01 were observed after stronger depolarizations. In conclusion, our results suggest that EX15 and RE01 positive modulation of Kv3.1 and Kv3.2 currents facilitate increased firing frequency in fast-spiking GABAergic interneurons.

  16. Kv1 channels selectively prevent dendritic hyperexcitability in rat Purkinje cells

    PubMed Central

    Khavandgar, Simin; Walter, Joy T; Sageser, Kristin; Khodakhah, Kamran

    2005-01-01

    Purkinje cells, the sole output of the cerebellar cortex, encode the timing signals required for motor coordination in their firing rate and activity pattern. Dendrites of Purkinje cells express a high density of P/Q-type voltage-gated calcium channels and fire dendritic calcium spikes. Here we show that dendritic subthreshold Kv1.2 subunit-containing Kv1 potassium channels prevent generation of random spontaneous calcium spikes. With Kv1 channels blocked, dendritic calcium spikes drive bursts of somatic sodium spikes and prevent the cell from faithfully encoding motor timing signals. The selective dendritic function of Kv1 channels in Purkinje cells allows them to effectively suppress dendritic hyperexcitability without hindering the generation of somatic action potentials. Further, we show that Kv1 channels also contribute to dendritic integration of parallel fibre synaptic input. Kv1 channels are often targeted to soma and axon and the data presented support a major dendritic function for these channels. PMID:16210348

  17. U.S. Army Corps of Engineers: Building Overhead Costs into Projects and Customers’ Views on Information Provided

    DTIC Science & Technology

    2013-06-01

    contact Anne-Marie Fennell at (202) 512-3841 or fennella@gao.gov. Page i GAO-13-528 Army Corps Overhead Process Letter 1...listed in appendix III. Sincerely yours, Anne-Marie Fennell Director, Natural Resources and Environment Agency Comments and Our Evaluation...Acknowledgments Page 31 GAO-13-528 Army Corps Overhead Process Anne-Marie Fennell , (202) 512-3841 or fennella@gao.gov In addition to the

  18. Cellular mechanisms and behavioral consequences of Kv1.2 regulation in the rat cerebellum

    PubMed Central

    Williams, Michael R; Fuchs, Jason R; Green, John T; Morielli, Anthony D

    2012-01-01

    The potassium channel Kv1.2 alpha-subunit is expressed in cerebellar Purkinje cell (PC) dendrites where its pharmacological inhibition increases excitability (Khavandgar et al., 2005). Kv1.2 is also expressed in cerebellar basket cell (BC) axon terminals (Sheng et al., 1994), where its blockade increases BC inhibition of PCs (Southan and Robertson, 1998a). Secretin receptors are also expressed both in PC dendrites and BC axon terminals (reviewed in (Yuan et al.). The effect of secretin on PC excitability is not yet known, but, like Kv1.2 inhibitors, secretin potently increases inhibitory input to PCs (Yung et al., 2001). This suggests secretin may act in part by suppressing Kv1.2. Receptor-mediated endocytosis is a mechanism of Kv1.2 suppression (Nesti et al., 2004). This process can be regulated by protein kinase A (PKA) (Connors et al., 2008). Since secretin receptors activate PKA (Wessels-Reiker et al., 1993), we tested the hypothesis that secretin regulates Kv1.2 trafficking in the cerebellum. Using cell surface protein biotinylation of rat cerebellar slices, we found secretin decreased cell-surface Kv1.2 levels by modulating Kv1.2 endocytic trafficking. This effect was mimicked by activating adenylate cyclase (AC) with forskolin, and was blocked by pharmacological inhibitors of AC or PKA. Imaging studies identified the BC axon terminal and Purkinje cell dendrites as loci of AC-dependent Kv1.2 trafficking. The physiological significance of secretin regulated Kv1.2 endocytosis is supported by our finding that infusion into the cerebellar cortex of either the Kv1.2 inhibitor Tityustoxin-Kα, or of the Kv1.2 regulator secretin, significantly enhances acquisition of eyeblink conditioning in rats. PMID:22764231

  19. Mapping the Interaction Anatomy of BmP02 on Kv1.3 Channel

    PubMed Central

    Wu, B.; Wu, B. F.; Feng, Y. J.; Tao, J.; Ji, Y. H.

    2016-01-01

    The potassium channel Kv 1.3 plays a vital part in the activation of T lymphocytes and is an attractive pharmacological target for autoimmune diseases. BmP02, a 28-residue peptide isolated from Chinese scorpion (Buthus martensi Karsch) venom, is a potent and selective Kv1.3 channel blocker. However, the mechanism through which BmP02 recognizes and inhibits the Kv1.3 channel is still unclear. In the present study, a complex molecular model of Kv1.3-BmP02 was developed by docking analysis and molecular dynamics simulations. From these simulations, it appears the large β-turn (residues 10–16) of BmP02 might be the binding interface with Kv 1.3. These results were confirmed by scanning alanine mutagenesis of BmP02, which identified His9, Lys11 and Lys13, which lie within BmP02’s β-turn, as key residues for interacting with Kv1.3. Based on these results and molecular modeling, two negatively charged residues of Kv1.3, D421 and D422, located in turret region, were predicted to act as the binding site for BmP02. Mutation of these residues reduced sensitivity of Kv 1.3 to BmP02 inhibition, suggesting that electrostatic interactions play a crucial role in Kv1.3-BmP02 interaction. This study revealed the molecular basis of Kv 1.3 recognition by BmP02 venom, and provides a novel interaction model for Kv channel-specific blocker complex, which may help guide future drug-design for Kv1.3-related channelopathies. PMID:27403813

  20. KV7 channels in the human detrusor: channel modulator effects and gene and protein expression.

    PubMed

    Bientinesi, Riccardo; Mancuso, Cesare; Martire, Maria; Bassi, Pier Francesco; Sacco, Emilio; Currò, Diego

    2017-02-01

    Voltage-gated type 7 K(+) (KV7 or KCNQ) channels regulate the contractility of various smooth muscles. With this study, we aimed to assess the role of KV7 channels in the regulation of human detrusor contractility, as well as the gene and protein expression of KV7 channels in this tissue. For these purposes, the isolated organ technique, RT-qPCR, and Western blot were used, respectively. XE-991, a selective KV7 channel blocker, concentration-dependently contracted the human detrusor; mean EC50 and Emax of XE-991-induced concentration-response curve were 14.1 μM and 28.8 % of the maximal bethanechol-induced contraction, respectively. Flupirtine and retigabine, selective KV7.2-7.5 channel activators, induced concentration-dependent relaxations of bethanechol-precontracted strips, with maximal relaxations of 51.6 and 51.8 % of the precontraction, respectively. XE-991 blocked the relaxations induced by flupirtine and retigabine. All five KCNQ genes were found to be expressed in the detrusor with KCNQ4 being the most expressed among them. Different bands, having sizes similar to some of reported KV7.1, 7.4, and 7.5 channel subunit isoforms, were detected in the detrusor by Western blot with the KV7.4 band being the most intense among them. In conclusion, KV7 channels contribute to set the basal tone of the human detrusor. In addition, KV7 channel activators significantly relax the detrusor. The KV7.4 channels are probably the most important KV7 channels expressed in the human detrusor. These data suggest that selective KV7.4 channel activators might represent new pharmacological tools for inducing therapeutic relaxation of the detrusor.

  1. Kv4.2 knockout mice demonstrate increased susceptibility to convulsant stimulation

    PubMed Central

    Barnwell, L. Forbes S.; Lugo, Joaquin N.; Lee, Wai Ling; Willis, Sarah E.; Gertz, Shira J.; Hrachovy, Richard A.; Anderson, Anne E.

    2010-01-01

    Purpose Kv4.2 subunits contribute to the pore-forming region of channels that express a transient, A-type K+ current (A-current) in hippocampal CA1 pyramidal cell dendrites. Here, the A-current plays an important role in signal processing and synaptic integration. Kv4.2 knockout mice show a near elimination of the A-current in area CA1 dendrites producing increased excitability in this region. In these studies, we evaluated young adult Kv4.2 knockout mice for spontaneous seizures and the response to convulsant stimulation in the whole animal in vivo and in hippocampal slices in vitro. Methods Electroencephalogram electrode-implanted Kv4.2 knockout and wildtype mice were observed for spontaneous behavioral and electrographic seizures. The latency to seizure and status epilepticus onset in Kv4.2 knockout and wildtype mice was assessed following intraperitoneal injection of kainate. Extracellular field potential recordings were performed in hippocampal slices from Kv4.2 knockout and wildtype mice following the bath application of bicuculline. Results No spontaneous behavioral or electrographic seizures were observed in Kv4.2 knockout mice. Following kainate, Kv4.2 knockout mice demonstrated a decreased seizure and status epilepticus latency as well as increased mortality compared to wildtype littermates. The background strain modified the seizure susceptibility phenotype in Kv4.2 knockout mice. In response to bicuculline, slices from Kv4.2 knockout mice exhibited an increase in epileptiform bursting in area CA1 as compared to wildtype littermates. Discussion These studies show that loss of Kv4.2 channels is associated with enhanced susceptibility to convulsant stimulation, supporting the concept that Kv4.2 deficiency may contribute to aberrant network excitability and regulate seizure threshold. PMID:19453702

  2. Mapping the Interaction Anatomy of BmP02 on Kv1.3 Channel

    NASA Astrophysics Data System (ADS)

    Wu, B.; Wu, B. F.; Feng, Y. J.; Tao, J.; Ji, Y. H.

    2016-07-01

    The potassium channel Kv 1.3 plays a vital part in the activation of T lymphocytes and is an attractive pharmacological target for autoimmune diseases. BmP02, a 28-residue peptide isolated from Chinese scorpion (Buthus martensi Karsch) venom, is a potent and selective Kv1.3 channel blocker. However, the mechanism through which BmP02 recognizes and inhibits the Kv1.3 channel is still unclear. In the present study, a complex molecular model of Kv1.3-BmP02 was developed by docking analysis and molecular dynamics simulations. From these simulations, it appears the large β-turn (residues 10–16) of BmP02 might be the binding interface with Kv 1.3. These results were confirmed by scanning alanine mutagenesis of BmP02, which identified His9, Lys11 and Lys13, which lie within BmP02’s β-turn, as key residues for interacting with Kv1.3. Based on these results and molecular modeling, two negatively charged residues of Kv1.3, D421 and D422, located in turret region, were predicted to act as the binding site for BmP02. Mutation of these residues reduced sensitivity of Kv 1.3 to BmP02 inhibition, suggesting that electrostatic interactions play a crucial role in Kv1.3-BmP02 interaction. This study revealed the molecular basis of Kv 1.3 recognition by BmP02 venom, and provides a novel interaction model for Kv channel-specific blocker complex, which may help guide future drug-design for Kv1.3-related channelopathies.

  3. The C-terminus of Kv7 channels: a multifunctional module.

    PubMed

    Haitin, Yoni; Attali, Bernard

    2008-04-01

    Kv7 channels (KCNQ) represent a family of voltage-gated K(+) channels which plays a prominent role in brain and cardiac excitability. Their physiological importance is underscored by the existence of mutations in human Kv7 genes, leading to severe cardiovascular and neurological disorders such as the cardiac long QT syndrome and neonatal epilepsy. Kv7 channels exhibit some structural and functional features that are distinct from other Kv channels. Notably, the Kv7 C-terminus is long compared to other K(+) channels and is endowed with characteristic structural domains, including coiled-coils, amphipatic alpha helices containing calmodulin-binding motifs and basic amino acid clusters. Here we provide a brief overview of current insights and as yet unsettled issues about the structural and functional attributes of the C-terminus of Kv7 channels. Recent data indicate that the proximal half of the Kv7 C-terminus associates with one calmodulin constitutively bound to each subunit. Epilepsy and long QT mutations located in this proximal region impair calmodulin binding and can affect channel gating, folding and trafficking. The distal half of the Kv7 C-terminus directs tetramerization, employing tandem coiled-coils. Together, the data indicate that the Kv7 C-terminal domain is a multimodular structure playing a crucial role in channel gating, assembly and trafficking as well as in scaffolding the channel complex with signalling proteins.

  4. Localization of Kv1.3 channels in presynaptic terminals of brainstem auditory neurons

    PubMed Central

    Gazula, Valeswara-Rao; Strumbos, John G.; Mei, Xiaofeng; Chen, Haijun; Rahner, Christoph; Kaczmarek, Leonard K.

    2010-01-01

    Elimination of the Kv1.3 voltage-dependent potassium channel gene produces striking changes in the function of the olfactory bulb, raising the possibility that this channel also influences other sensory systems. We have examined the cellular and subcellular localization of Kv1.3 in the Medial Nucleus of the Trapezoid Body (MNTB) in the auditory brainstem, a nucleus in which neurons fire at high rates with high temporal precision. A clear gradient of Kv1.3 immunostaining along the lateral to medial tonotopic axis of the MNTB was detected. Highest levels were found in the lateral region of the MNTB, which corresponds to neurons that respond selectively to low frequency auditory stimuli. Previous studies have demonstrated that MNTB neurons and their afferent inputs from the cochlear nucleus express three other members of the Kv1 family, Kv1.1, Kv1.2 and Kv1.6. Nevertheless, confocal microscopy of MNTB sections co-immunostained for Kv1.3 with these subunits revealed that the distribution of Kv1.3 differed significantly from other Kv1 family subunits. In particular, no axonal staining of Kv1.3 was detected and most prominent labeling was in structures surrounding the somata of the principal neurons, suggesting specific localization to the large calyx of Held presynaptic endings that envelop the principal cells. The presence of Kv1.3 in presynaptic terminals was confirmed by co-immunolocalization with the synaptic markers synaptophysin, syntaxin, and synaptotagmin and by immunogold electron microscopy. Kv1.3 immunogold particles in the terminals were arrayed along the plasma membrane and on internal vesicular structures. To confirm these patterns of staining, we carried out immunolabeling on sections from Kv1.3−/− mice. No immunoreactivity could be detected in Kv1.3−/− mice either at the light level or in immunogold experiments. The finding of a tonotopic gradient in presynaptic terminals suggests that Kv1.3 may regulate neurotransmitter release differentially in

  5. Expression and function of K(V)2-containing channels in human urinary bladder smooth muscle.

    PubMed

    Hristov, Kiril L; Chen, Muyan; Afeli, Serge A Y; Cheng, Qiuping; Rovner, Eric S; Petkov, Georgi V

    2012-06-01

    The functional role of the voltage-gated K(+) (K(V)) channels in human detrusor smooth muscle (DSM) is largely unexplored. Here, we provide molecular, electrophysiological, and functional evidence for the expression of K(V)2.1, K(V)2.2, and the electrically silent K(V)9.3 subunits in human DSM. Stromatoxin-1 (ScTx1), a selective inhibitor of K(V)2.1, K(V)2.2, and K(V)4.2 homotetrameric channels and of K(V)2.1/9.3 heterotetrameric channels, was used to examine the role of these channels in human DSM function. Human DSM tissues were obtained during open bladder surgeries from patients without a history of overactive bladder. Freshly isolated human DSM cells were studied using RT-PCR, immunocytochemistry, live-cell Ca(2+) imaging, and the perforated whole cell patch-clamp technique. Isometric DSM tension recordings of human DSM isolated strips were conducted using tissue baths. RT-PCR experiments showed mRNA expression of K(V)2.1, K(V)2.2, and K(V)9.3 (but not K(V)4.2) channel subunits in human isolated DSM cells. K(V)2.1 and K(V)2.2 protein expression was confirmed by Western blot analysis and immunocytochemistry. Perforated whole cell patch-clamp experiments revealed that ScTx1 (100 nM) inhibited the amplitude of the voltage step-induced K(V) current in freshly isolated human DSM cells. ScTx1 (100 nM) significantly increased the intracellular Ca(2+) level in DSM cells. In human DSM isolated strips, ScTx1 (100 nM) increased the spontaneous phasic contraction amplitude and muscle force, and enhanced the amplitude of the electrical field stimulation-induced contractions within the range of 3.5-30 Hz stimulation frequencies. These findings reveal that ScTx1-sensitive K(V)2-containing channels are key regulators of human DSM excitability and contractility and may represent new targets for pharmacological or genetic intervention for bladder dysfunction.

  6. Bab Eshtar Substation 11 kV Feeder Cable. Mosul, Iraq

    DTIC Science & Technology

    2006-10-17

    Item Unit QTY U price Total in US$ 3x150mm2 , 11kv , XLPE insulated cable M 10,000 43 430000 Straight outdoor heat shrinkable splice kit for 3x150mm2...11kv, XLPE cable Ea 15 325 4875 Indoor Heat shrinkable termination kit for 3x150mm2, 11kv XLPE cable Ea 9 250 2250 Outdoor Heat shrinkable...termination kit for 3x150mm2, 11kv XLPE cable Ea 5 275 1375 2 Ring-main feeders with cabinet Ea 2 18000 36000 Excavated sand m3 550 30 16500 Fine soil m3 350

  7. 30-kV proton injector for PIGMI

    SciTech Connect

    Hamm, R.W.; Mueller, D.W.; Sturgess, R.G.

    1981-01-01

    A 30-kV proton injector designed for matching a 31-mA proton beam into the radio-frequency quadrupole (RFQ) section of the PIGMI accelerator has been constructed and tested. This injector uses a small efficient duoplasmatron ion source and a single-gap extraction system for creating a convergent ion beam, and a three-element unipotential einzel lens for focusing the ion beam into the RFQ. A description of this prototype injector is presented, along with the experimental data obtained during the testing of this system.

  8. V4641 Sgr and KV UMa. Two black hole candidates

    NASA Astrophysics Data System (ADS)

    Chuprikov, A.; Guirin, I.

    We have analized the results of processing of the NRAO archive VLA and VLBA data for two star objects titled V4641 Sgr (J1819-2524) and KV UMa (X1118+4802). Some radio images of both sources for some frequency ranges are presented. Data have been processed with the software project titled 'Astro Space Locator' (ASL for Windows). The Multi Frequency Synthesis (MFS) method has been used for reconstruction of radio maps. Images of both sources are presented. Any polarization phenomena are not taken into account. We present results of processing of data of RR polarization for all the observational sessions.

  9. Pollution performance of 110 kV metal oxide arresters

    SciTech Connect

    Chrzan, K.; Pohl, Z.; Grzybowski, S.; Koehler, W.

    1997-04-01

    Pollution test results of single unit 110 kV metal oxide surge arresters with porcelain housing according to the solid layer and salt fog methods are presented. During 6 hours of testing, the internal and external charge and maximum temperature along the varistor column were measured. The formation of single stable dry bands on the housing was often observed, especially during salt fog tests. In such cases, the varistor temperature can reach about 70 C. The simple electrical model of the arrester enabling calculations of voltages and currents as a function of arrester and pollution parameters is shown.

  10. 10-Joule 200 kV Mini Marx

    DTIC Science & Technology

    1985-06-01

    A low-energy Marx generator was designed at Los Alamos as a spark gap trigger. Since the initial report1 the design has been improved and is now...manufactured commercially. The Mini Marx has a risetime of less than 2 ns to over 200 kV measured in to a 23 omega load. The power output approaches one...gigawatt. The Mini Marx can multichannel field distortion gaps or fire a number of gaps with little gap-to-gap isolation. It has also been used to

  11. Comparison of the NIST and NPL Air Kerma Standards Used for X-Ray Measurements Between 10 kV and 80 kV.

    PubMed

    O'Brien, M; Lamperti, P; Williams, T; Sander, T

    2000-01-01

    A direct comparison was made between the air kerma primary standards used for the measurements of low-energy x rays at the National Institute of Standards and Technology (NIST) and the National Physical Laboratory (NPL). The comparison was conducted at the NPL using NPL reference radiation qualities between 10 kV and 80 kV. The results show the primary air-kerma standards to agree within 0.6 % of their values for beam qualities up to 80 kV.

  12. High power thyristors with 5 kV blocking voltage. Volume 1: Development of high-voltage-thyristors (4.5 kV) with good dynamic properties

    NASA Technical Reports Server (NTRS)

    Lock, K.; Patalong, H.; Platzoeder, K.

    1979-01-01

    Using neutron irradiated silicon with considerably lower spread in resistivity as compared to conventionally doped silicon it was possible to produce power thyristors with breakdown voltages between 3.5 kV and 5.5 kV. The thyristor pellets have a diameter of 50 mm. Maximum average on-state currents of 600 to 800 A can be reached with these elements. The dynamic properties of the thryistors could be improved to allow standard applications up to maximum repetitive voltages of 4.5 kV.

  13. Balancing the Lifetime and Storage Overhead on Error Correction for Phase Change Memory.

    PubMed

    An, Ning; Wang, Rui; Gao, Yuan; Yang, Hailong; Qian, Depei

    2015-01-01

    As DRAM is facing the scaling difficulty in terms of energy cost and reliability, some nonvolatile storage materials were proposed to be the substitute or supplement of main memory. Phase Change Memory (PCM) is one of the most promising nonvolatile memory that could be put into use in the near future. However, before becoming a qualified main memory technology, PCM should be designed reliably so that it can ensure the computer system's stable running even when errors occur. The typical wear-out errors in PCM have been well studied, but the transient errors, that caused by high-energy particles striking on the complementary metal-oxide semiconductor (CMOS) circuit of PCM chips or by resistance drifting in multi-level cell PCM, have attracted little focus. In this paper, we propose an innovative mechanism, Local-ECC-Global-ECPs (LEGE), which addresses both soft errors and hard errors (wear-out errors) in PCM memory systems. Our idea is to deploy a local error correction code (ECC) section to every data line, which can detect and correct one-bit errors immediately, and a global error correction pointers (ECPs) buffer for the whole memory chip, which can be reloaded to correct more hard error bits. The local ECC is used to detect and correct the unknown one-bit errors, and the global ECPs buffer is used to store the corrected value of hard errors. In comparison to ECP-6, our method provides almost identical lifetimes, but reduces approximately 50% storage overhead. Moreover, our structure reduces approximately 3.55% access latency overhead by increasing 1.61% storage overhead compared to PAYG, a hard error only solution.

  14. Electromyographic and kinetic comparison of the back squat and overhead squat.

    PubMed

    Aspe, Rodrigo R; Swinton, Paul A

    2014-10-01

    The purpose of this study was to compare muscle activity and kinetics during the back squat and overhead squat performed at 3 relative intensities (60, 75, and 90% 3 repetition maximum). Fourteen subjects (age, 26 ± 7 years; height, 182.5 ± 13.5 cm; body mass, 90.5 ± 17.5 kg) performed each exercise using a within-subjects crossover design. In addition, a selection of trunk isolation exercises were included to provide additional comparisons. Squats were performed on a force platform with electromyographic activity of the anterior deltoid, rectus abdominis (RA), external oblique (EO), erector spinae (ES), gluteus maximus, vastus lateralis, biceps femoris, and lateral gastrocnemius recorded throughout. The overhead squat demonstrated significantly greater (p ≤ 0.05) activity in the anterior trunk muscles (RA and EO) during the eccentric phase. However, the magnitudes of the differences were relatively small (approximately 2-7%). In contrast, the back squat displayed significantly greater (p ≤ 0.05) activity in the posterior aspect of the trunk ES and all lower-body muscles during the concentric phase. Kinetic comparisons revealed that significantly greater peak force (p ≤ 0.05) was developed during the back squat. Electromyographic comparisons between the trunk isolation exercises and squat variations demonstrated substantially greater anterior trunk activity during the isolation exercises, whereas the highest activity in the posterior aspect of the trunk was obtained during the squats (p ≤ 0.05). The results of the study do not support the hypothesis that the overhead squat provides a substantially greater stimulus for developing the trunk musculature compared with the back squat.

  15. Stichodactyla helianthus peptide, a pharmacological tool for studying Kv3.2 channels.

    PubMed

    Yan, Lizhen; Herrington, James; Goldberg, Ethan; Dulski, Paula M; Bugianesi, Randal M; Slaughter, Robert S; Banerjee, Priya; Brochu, Richard M; Priest, Birgit T; Kaczorowski, Gregory J; Rudy, Bernardo; Garcia, Maria L

    2005-05-01

    Voltage-gated potassium (Kv) channels regulate many physiological functions and represent important therapeutic targets in the treatment of several clinical disorders. Although some of these channels have been well-characterized, the study of others, such as Kv3 channels, has been hindered because of limited pharmacological tools. The current study was initiated to identify potent blockers of the Kv3.2 channel. Chinese hamster ovary (CHO)-K1 cells stably expressing human Kv3.2b (CHO-K1.hKv3.2b) were established and characterized. Stichodactyla helianthus peptide (ShK), isolated from S. helianthus venom and a known high-affinity blocker of Kv1.1 and Kv1.3 channels, was found to potently inhibit 86Rb+ efflux from CHO-K1.hKv3.2b (IC50 approximately 0.6 nM). In electrophysiological recordings of Kv3.2b channels expressed in Xenopus laevis oocytes or in planar patch-clamp studies, ShK inhibited hKv3.2b channels with IC50 values of approximately 0.3 and 6 nM, respectively. Despite the presence of Kv3.2 protein in human pancreatic beta cells, ShK has no effect on the Kv current of these cells, suggesting that it is unlikely that homotetrameric Kv3.2 channels contribute significantly to the delayed rectifier current of insulin-secreting cells. In mouse cortical GABAergic fast-spiking interneurons, however, application of ShK produced effects consistent with the blockade of Kv3 channels (i.e., an increase in action potential half-width, a decrease in the amplitude of the action potential after hyperpolarization, and a decrease in maximal firing frequency in response to depolarizing current injections). Taken together, these results indicate that ShK is a potent inhibitor of Kv3.2 channels and may serve as a useful pharmacological probe for studying these channels in native preparations.

  16. Wild Horse 69-kV transmission line environmental assessment

    SciTech Connect

    1996-12-01

    Hill County Electric Cooperative Inc. (Hill County) proposes to construct and operate a 69-kV transmission line from its North Gildford Substation in Montana north to the Canadian border. A vicinity project area map is enclosed as a figure. TransCanada Power Corporation (TCP), a Canadian power-marketing company, will own and construct the connecting 69-kV line from the international border to Express Pipeline`s pump station at Wild Horse, Alberta. This Environmental Assessment is prepared for the Department of Energy (DOE) as lead federal agency to comply with the requirements of the National Environmental Policy Act (NEPA), as part of DOE`s review and approval process of the applications filed by Hill County for a DOE Presidential Permit and License to Export Electricity to a foreign country. The purpose of the proposed line is to supply electric energy to a crude oil pump station in Canada, owned by Express Pipeline Ltd. (Express). The pipeline would transport Canadian-produced oil from Hardisty, Alberta, Canada, to Caster, Wyoming. The Express Pipeline is scheduled to be constructed in 1996--97 and will supply crude oil to refineries in Wyoming and the midwest.

  17. Corona performance of a compact 230-kV line

    SciTech Connect

    Chartier, V.L.; Blair, D.E.; Easley, M.D.; Raczkowski, R.T.

    1995-01-01

    Permitting requirements and the acquisition of new rights-of-way for transmission facilities has in recent years become increasingly difficult for most utilities, including Puget Sound Power and Light Company. In order to maintain a high degree of reliability of service while being responsive to public concerns regarding the siting of high voltage (HV) transmission facilities, Puget Power has found it necessary to more heavily rely upon the use of compact lines in franchise corridors. Compaction does, however, precipitate increased levels of audible noise (AN) and radio and TV interference (RI and TVI) due to corona on the conductors and insulator assemblies. Puget Power relies upon the Bonneville Power Administration (BPA) Corona and Field Effects computer program to calculate AN and RI for new lines. Since there was some question of the program`s ability to accurately represent quiet 230-kV compact designs, a joint project was undertaken with BPA to verify the program`s algorithms. Long-term measurements made on an operating Puget Power 230-kV compact line confirmed the accuracy of BPA`s AN model; however, the RI measurements were much lower than predicted by the BPA and other programs. This paper also describes how the BPA computer program can be used to calculate the voltage needed to expose insulator assemblies to the correct electric field in single test setups in HV laboratories.

  18. Corona performance of a compact 230-kV line

    SciTech Connect

    Chartier, V.L.; Blair, D.E.; Easley, M.D.; Raczkowski, R.T.

    1994-12-31

    Permitting requirements and the acquisition of new rights-of-way for transmission facilities has in recent years become increasingly difficult for most utilities, including Puget Sound Power and Light Company. In order to maintain a high degree of reliability of service while being responsive to public concerns regarding the siting of high voltage (HV) transmission facilities, Puget Power has found it necessary to more heavily rely upon the use of compact lines in franchise corridors. Compaction does, however, precipitant increased levels of audible noise (AN) and radio and TV interference (RI and TVI) due to corona on the conductors and insulator assemblies. Puget Power relies upon the Bonneville Power Administration (BPA) Corona and Field Effects computer program to calculate AN and RI for new lines. Since there was some question of the program`s ability to accurately represent quiet 230-kV compact designs, a joint project was undertaken with BPA to verify the program`s algorithms. Long-term measurements made on an operating Puget Power 230-kV compact line confirmed the accuracy of BPA`s AN model; however, the RI measurements were much lower than predicted by the BPA computer and other programs. This paper also describes how the BPA computer program can be used to calculate the voltage needed to expose insulator assemblies to the correct electric field in single test setups in HV laboratories.

  19. Design of the Atlas 240 kV Marx modules

    SciTech Connect

    Bowman, D.W.; Bennett, G.; Biehl, F.

    1997-06-01

    A prototype 240 kV, oil-insulated Marx module has been designed and constructed at the Los Alamos National Laboratory (LANL). The prototype will be used for testing and certifying the design of the Marx module and certain components, including the closing switches, series resistor, and the capacitors themselves. The prototype will also be used to evaluate proposed mechanical systems designs. Information gained from the construction and testing of the 4-capacitor prototype will be folded into the design of the 16-capacitor maintenance unit. The prototype module consists of four 60 kV capacitors, two closing switches, one shunt resistor, and one series resistor. Cables are used to deliver the current to a dummy load scaled to match Atlas system parameters. The Marx unit is contained in a structure made from G-10, suspended from a steel frame that also serves to support components of the trigger, charging, and control system. Appropriate safety and charging systems are an integral part of the prototype design.

  20. Kv4 potassium channels modulate hippocampal EPSP-spike potentiation and spatial memory in rats.

    PubMed

    Truchet, Bruno; Manrique, Christine; Sreng, Leam; Chaillan, Franck A; Roman, François S; Mourre, Christiane

    2012-06-14

    Kv4 channels regulate the backpropagation of action potentials (b-AP) and have been implicated in the modulation of long-term potentiation (LTP). Here we showed that blockade of Kv4 channels by the scorpion toxin AmmTX3 impaired reference memory in a radial maze task. In vivo, AmmTX3 intracerebroventricular (i.c.v.) infusion increased and stabilized the EPSP-spike (E-S) component of LTP in the dentate gyrus (DG), with no effect on basal transmission or short-term plasticity. This increase in E-S potentiation duration could result from the combination of an increase in excitability of DG granular cells with a reduction of GABAergic inhibition, leading to a strong reduction of input specificity. Radioactive in situ hybridization (ISH) was used to evaluate the amounts of Kv4.2 and Kv4.3 mRNA in brain structures at different stages of a spatial learning task in naive, pseudoconditioned, and conditioned rats. Significant differences in Kv4.2 and Kv4.3 mRNA levels were observed between conditioned and pseudoconditioned rats. Kv4.2 and Kv4.3 mRNA levels were transiently up-regulated in the striatum, nucleus accumbens, retrosplenial, and cingulate cortices during early stages of learning, suggesting an involvement in the switch from egocentric to allocentric strategies. Spatial learning performance was positively correlated with the levels of Kv4.2 and Kv4.3 mRNAs in several of these brain structures. Altogether our findings suggest that Kv4 channels could increase the signal-to-noise ratio during information acquisition, thereby allowing a better encoding of the memory trace.

  1. Sites and Functional Consequence of Alkylphenol Anesthetic Binding to Kv1.2 Channels.

    PubMed

    Bu, Weiming; Liang, Qiansheng; Zhi, Lianteng; Maciunas, Lina; Loll, Patrick J; Eckenhoff, Roderic G; Covarrubias, Manuel

    2017-02-15

    Inhalational general anesthetics, such as sevoflurane and isoflurane, modulate a subset of brain Kv1 potassium channels. However, the Kv1.2 channel is resistant to propofol, a commonly used intravenous alkylphenol anesthetic. We hypothesize that propofol binds to a presumed pocket involving the channel's S4-S5 linker, but functional transduction is poor and, therefore, propofol efficacy is low. To test this hypothesis, we used a photoactive propofol analog (meta-aziPropofol = AziPm) to directly probe binding and electrophysiological and mutational analyses in Xenopus oocytes to probe function. We find that AziPm photolabels L321 in the S4-S5 linker of both the wild-type Kv1.2 and a mutant Kv1.2 (G329 T) with a novel gating phenotype. Furthermore, whereas propofol does not significantly modulate Kv1.2 WT but robustly potentiates Kv1.2 G329T, AziPm inhibits Kv1.2 WT and also potentiates Kv1.2 G329T. Kv1.2 modulation by AziPm was abolished by two mutations that decreased hydrophobicity at L321 (L321A and L321F), confirming the specific significance of the S4-S5 linker in the mechanism of general anesthetic modulation. Since AziPm binds to Kv1.2 G329T and shares the propofol ability to potentiate this mutant, the parent propofol likely also binds to the Kv1.2 channel. However, binding and alkylphenol-induced transduction are seemingly sensitive to the conformation of the S4-S5 linker site (altered by G329T) and subtle differences in the chemical structures of propofol and AziPm. Overall, the results are consistent with a mechanism of general anesthetic modulation that depends on the complementarity of necessary ligand binding and permissive ion channel conformations that dictate modulation and efficacy.

  2. Behavioural and functional characterization of Kv10.1 (Eag1) knockout mice

    PubMed Central

    Ufartes, Roser; Schneider, Tomasz; Mortensen, Lena Sünke; de Juan Romero, Camino; Hentrich, Klaus; Knoetgen, Hendrik; Beilinson, Vadim; Moebius, Wiebke; Tarabykin, Victor; Alves, Frauke; Pardo, Luis A.; Rawlins, J. Nicholas P.; Stuehmer, Walter

    2013-01-01

    Kv10.1 (Eag1), member of the Kv10 family of voltage-gated potassium channels, is preferentially expressed in adult brain. The aim of the present study was to unravel the functional role of Kv10.1 in the brain by generating knockout mice, where the voltage sensor and pore region of Kv10.1 were removed to render non-functional proteins through deletion of exon 7 of the KCNH1 gene using the ‘3 Lox P strategy’. Kv10.1-deficient mice show no obvious alterations during embryogenesis and develop normally to adulthood; cortex, hippocampus and cerebellum appear anatomically normal. Other tests, including general health screen, sensorimotor functioning and gating, anxiety, social behaviour, learning and memory did not show any functional aberrations in Kv10.1 null mice. Kv10.1 null mice display mild hyperactivity and longer-lasting haloperidol-induced catalepsy, but there was no difference between genotypes in amphetamine sensitization and withdrawal, reactivity to apomorphine and haloperidol in the prepulse inhibition tests or to antidepressants in the haloperidol-induced catalepsy. Furthermore, electrical properties of Kv10.1 in cerebellar Purkinje cells did not show any difference between genotypes. Bearing in mind that Kv10.1 is overexpressed in over 70% of all human tumours and that its inhibition leads to a reduced tumour cell proliferation, the fact that deletion of Kv10.1 does not show a marked phenotype is a prerequisite for utilizing Kv10.1 blocking and/or reduction techniques, such as siRNA, to treat cancer. PMID:23424202

  3. Behavioural and functional characterization of Kv10.1 (Eag1) knockout mice.

    PubMed

    Ufartes, Roser; Schneider, Tomasz; Mortensen, Lena Sünke; de Juan Romero, Camino; Hentrich, Klaus; Knoetgen, Hendrik; Beilinson, Vadim; Moebius, Wiebke; Tarabykin, Victor; Alves, Frauke; Pardo, Luis A; Rawlins, J Nicholas P; Stuehmer, Walter

    2013-06-01

    Kv10.1 (Eag1), member of the Kv10 family of voltage-gated potassium channels, is preferentially expressed in adult brain. The aim of the present study was to unravel the functional role of Kv10.1 in the brain by generating knockout mice, where the voltage sensor and pore region of Kv10.1 were removed to render non-functional proteins through deletion of exon 7 of the KCNH1 gene using the '3 Lox P strategy'. Kv10.1-deficient mice show no obvious alterations during embryogenesis and develop normally to adulthood; cortex, hippocampus and cerebellum appear anatomically normal. Other tests, including general health screen, sensorimotor functioning and gating, anxiety, social behaviour, learning and memory did not show any functional aberrations in Kv10.1 null mice. Kv10.1 null mice display mild hyperactivity and longer-lasting haloperidol-induced catalepsy, but there was no difference between genotypes in amphetamine sensitization and withdrawal, reactivity to apomorphine and haloperidol in the prepulse inhibition tests or to antidepressants in the haloperidol-induced catalepsy. Furthermore, electrical properties of Kv10.1 in cerebellar Purkinje cells did not show any difference between genotypes. Bearing in mind that Kv10.1 is overexpressed in over 70% of all human tumours and that its inhibition leads to a reduced tumour cell proliferation, the fact that deletion of Kv10.1 does not show a marked phenotype is a prerequisite for utilizing Kv10.1 blocking and/or reduction techniques, such as siRNA, to treat cancer.

  4. Kv3 voltage-gated potassium channels regulate neurotransmitter release from mouse motor nerve terminals.

    PubMed

    Brooke, Ruth E; Moores, Thomas S; Morris, Neil P; Parson, Simon H; Deuchars, Jim

    2004-12-01

    Voltage-gated potassium (Kv) channels are critical to regulation of neurotransmitter release throughout the nervous system but the roles and identity of the subtypes involved remain unclear. Here we show that Kv3 channels regulate transmitter release at the mouse neuromuscular junction (NMJ). Light- and electron-microscopic immunohistochemistry revealed Kv3.3 and Kv3.4 subunits within all motor nerve terminals of muscles examined [transversus abdominus, lumbrical and flexor digitorum brevis (FDB)]. To determine the roles of these Kv3 subunits, intracellular recordings were made of end-plate potentials (EPPs) in FDB muscle fibres evoked by electrical stimulation of tibial nerve. Tetraethylammonium (TEA) applied at low concentrations (0.05-0.5 mM), which blocks only a few known potassium channels including Kv3 channels, did not affect muscle fibre resting potential but significantly increased the amplitude of all EPPs tested. Significantly, this effect of TEA was still observed in the presence of the large-conductance calcium-activated potassium channel blockers iberiotoxin (25-150 nM) and Penitrem A (100 nM), suggesting a selective action on Kv3 subunits. Consistent with this, 15-microM 4-aminopyridine, which blocks Kv3 but not large-conductance calcium-activated potassium channels, enhanced evoked EPP amplitude. Unexpectedly, blood-depressing substance-I, a toxin selective for Kv3.4 subunits, had no effect at 0.05-1 microM. The combined presynaptic localization of Kv3 subunits and pharmacological enhancement of EPP amplitude indicate that Kv3 channels regulate neurotransmitter release from presynaptic terminals at the NMJ.

  5. Synthesis of psoralen derivatives and their blocking effect of hKv1.5 channel.

    PubMed

    Eun, Jae Soon; Kim, Kwang Sik; Kim, Han Na; Park, Seon Ah; Ma, Tian-Ze; Lee, Kyung A; Kim, Dae Keun; Kim, Hyung Kyo; Kim, In Su; Jung, Young Hoon; Zee, Ok Pyo; Yoo, Dong Jin; Kwak, Yong Geun

    2007-02-01

    Previously, we found that a furocoumarin derivative, psoralen (7H-furo[3,2-g][1]benzopyran-7-one), blocked a human Kv1.5 potassium channel (hKv1.5) and has a potential antiarrhythmic effect. In the present study, to develop more potent hKv1.5 blockers or antiarrhythmic drugs, we synthesized ten psoralen derivatives and examined their blocking effects on hKv1.5 stably expressed in Ltk cells. Among the newly synthesized psoralen derivatives, three derivatives (Compounds 5, 9 and 10) showed the open channel-blocking effect. Compound 9 among them was the most potent in blocking hKv1.5. We found that compound 9, one of the psoralen derivatives, inhibited the hKv1.5 current in a concentration-, use- and voltage-dependent manner with an IC50 value of 27.4 +/- 5.1 nM at +60 mV. Compound 9 accelerated the inactivation kinetics of the hKv1.5 channel, slowed the deactivation kinetics of hKv1.5 current resulting in a tail crossover phenomenon. Compound 9 inhibited hKv1.5 current in a use-dependent manner. These results indicate that compound 9, one of psoralen derivatives, acts on hKv1.5 channel as an open channel blocker and is much more potent than psoralen in blocking hKv1.5 channel. If further studies were done, compound 9 might be an ideal antiarrhythmic drug for atrial fibrillation.

  6. Non-data-communication overheads in MPI : analysis on Blue Gene/P.

    SciTech Connect

    Balaji, P.; Chan, A.; Gropp, W.; Thakur, R.; Lusk, E.

    2008-01-01

    Modern HEC systems, such as Blue Gene/P, rely on achieving high-performance by using the parallelism of a massive number of low-frequency/low-power processing cores. This means that the local pre- and post-communication processing required by the MPI stack might not be very fast, owing to the slow processing cores. Similarly, small amounts of serialization within the MPI stack that were acceptable on small/medium systems can be brutal on massively parallel systems. In this paper, we study different non-data-communication overheads within the MPI implementation on the IBM Blue Gene/P system.

  7. Comparison of CAP88 and MCNP for Overhead Gamma-emitting Plumes

    SciTech Connect

    Mcnaughton, Michael; Gillis, Jessica Mcdonnel; McClory, Aysha Reede; Whicker, Jeffrey Jay; Fuehne, David Patrick

    2016-01-08

    The purpose of this paper is to use the Monte Carlo N-Particle Code (MCNP) to investigate the dose from gamma-emitting radionuclides such as Carbon-11 when a plume passes overhead. MCNP results are compared with results from the EPA program, CAP88. In some cases, typically near the source during stable conditions, the CAP88 results are less than the MCNP results. However, in the case of a receptor 800 m from a source at the Los Alamos Neutron Science Center (LANSCE), the CAP88 result is greater than the MCNP result.

  8. Characterization Results for the 2014 HTF 3H & 2H Evaporator Overhead Samples

    SciTech Connect

    Washington, A.

    2015-05-11

    This report tabulates the radiochemical analysis of the 3H and 2H evaporator overhead samples for 137Cs, 90Sr, and 129I to meet the requirements in the Effluent Treatment Project (ETP) Waste Acceptance Criteria (WAC) (rev. 6). This report identifies the sample receipt date, preparation method, and analysis performed in the accumulation of the listed values. All data was found to be within the ETP WAC (rev. 6) specification for the Waste Water Collection Tanks (WWCT).

  9. Low overhead and nonlinear-tolerant adaptive zero-guard-interval CO-OFDM.

    PubMed

    Wang, Wei; Zhuge, Qunbi; Gao, Yuliang; Qiu, Meng; Morsy-Osman, Mohamed; Chagnon, Mathieu; Xu, Xian; Plant, David V

    2014-07-28

    We propose an adaptive channel estimation (CE) method for zero-guard-interval (ZGI) coherent optical (CO)-OFDM systems, and demonstrate its performance in a single channel 28 Gbaud polarization-division multiplexed ZGI CO-OFDM experiment with only 1% OFDM processing overhead. We systematically investigate its robustness against various transmission impairments including residual chromatic dispersion, polarization-mode dispersion, state of polarization rotation, sampling frequency offset and fiber nonlinearity. Both experimental and numerical results show that the adaptive CE-aided ZGI CO-OFDM is highly robust against these transmission impairments in fiber optical transmission systems.

  10. Deletion of the Kv2.1 delayed rectifier potassium channel leads to neuronal and behavioral hyperexcitability

    PubMed Central

    Speca, David J.; Ogata, Genki; Mandikian, Danielle; Bishop, Hannah I.; Wiler, Steve W.; Eum, Kenneth; Wenzel, H. Jürgen; Doisy, Emily T.; Matt, Lucas; Campi, Katharine L.; Golub, Mari S.; Nerbonne, Jeanne M.; Hell, Johannes W.; Trainor, Brian C.; Sack, Jon T.; Schwartzkroin, Philip A.; Trimmer, James S.

    2014-01-01

    The Kv2.1 delayed rectifier potassium channel exhibits high-level expression in both principal and inhibitory neurons throughout the central nervous system, including prominent expression in hippocampal neurons. Studies of in vitro preparations suggest that Kv2.1 is a key yet conditional regulator of intrinsic neuronal excitability, mediated by changes in Kv2.1 expression, localization and function via activity-dependent regulation of Kv2.1 phosphorylation. Here we identify neurological and behavioral deficits in mutant (Kv2.1−/−) mice lacking this channel. Kv2.1−/− mice have grossly normal characteristics. No impairment in vision or motor coordination was apparent, although Kv2.1−/− mice exhibit reduced body weight. The anatomic structure and expression of related Kv channels in the brains of Kv2.1−/− mice appears unchanged. Delayed rectifier potassium current is diminished in hippocampal neurons cultured from Kv2.1−/− animals. Field recordings from hippocampal slices of Kv2.1−/− mice reveal hyperexcitability in response to the convulsant bicuculline, and epileptiform activity in response to stimulation. In Kv2.1−/− mice, long-term potentiation at the Schaffer collateral – CA1 synapse is decreased. Kv2.1−/− mice are strikingly hyperactive, and exhibit defects in spatial learning, failing to improve performance in a Morris Water Maze task. Kv2.1−/− mice are hypersensitive to the effects of the convulsants flurothyl and pilocarpine, consistent with a role for Kv2.1 as a conditional suppressor of neuronal activity. Although not prone to spontaneous seizures, Kv2.1−/− mice exhibit accelerated seizure progression. Together, these findings suggest homeostatic suppression of elevated neuronal activity by Kv2.1 plays a central role in regulating neuronal network function. PMID:24494598

  11. Brain expression of Kv3 subunits during development, adulthood and aging and in a murine model of Alzheimer's disease.

    PubMed

    Boda, Enrica; Hoxha, Eriola; Pini, Alessandro; Montarolo, Francesca; Tempia, Filippo

    2012-03-01

    In neurons, voltage-dependent Kv3 potassium channels are essential for the generation of action potentials at high frequency. A dysregulation of the Kv3.1 and Kv3.4 channel subunits has been suggested to contribute to neuronal and glial alterations in Alzheimer's disease, but a quantitative evaluation of these subunits in a mouse model of the pathology is still lacking. We analysed the profile of expression of the four Kv3 subunits by quantitative reverse transcription PCR and Western blot in the whole mouse brain and in dissected brain regions (olfactory bulb, septum, neocortex, hippocampus, brainstem and cerebellum) from 14 days after conception to 18 months after birth. In addition, we measured the levels of Kv3.1 and Kv3.4 messenger RNAs (mRNAs) and proteins in neocortex and hippocampus of APPPS1 mice, a transgenic model of Alzheimer's disease. Although all Kv3 transcripts were significantly expressed in embryonic age in whole brain extracts, only Kv3.1, Kv3.2 and Kv3.4 subunit proteins were present, suggesting a novel role for Kv3 channels at this developmental stage. With the exception of Kv3.4, during postnatal development, Kv3 transcripts and proteins showed a progressive increase in expression and reached an asymptote in adulthood, suggesting that the increase in Kv3 expression during development might contribute to the maturation of the electrical activity of neurons. During aging, Kv3 expression was rather stable. In contrast, in the neocortex of aged APPPS1 mice, Kv3.1 mRNA and protein levels were significantly lower compared to wild type, suggesting that a decrease in Kv3 currents could play a role in the cognitive symptoms of Alzheimer's disease.

  12. An assessment of GafChromic film for measuring 50 kV and 100 kV percentage depth dose curves.

    PubMed

    Fletcher, Claire Lesley; Mills, John A

    2008-06-07

    Percentage depth dose (PDD) curves were obtained for 50 kV and 100 kV x-rays on a Gulmay Medical D3000 DXR unit. Different dosimetry systems were compared including a Scanditronix Wellhofer small volume cylindrical ion chamber, a Wellhofer photon PFD diode, a PTW soft x-ray parallel plate chamber (N23342) and two types of radiochromic film: GafChromic EBT and GafChromic MD55. The PDD curves were also compared to BEAMnrc Monte Carlo predictions. GafChromic film was found to be a valid choice of dosimeter for measuring percentage depth dose curves at 100 kV and 50 kV. All the dosimeters showed agreement with predictions at depths greater than 10 mm, while near the surface GafChromic film and PFD diodes give the best agreement to Monte Carlo values.

  13. Anti-voltage-gated potassium channel Kv1.4 antibodies in myasthenia gravis.

    PubMed

    Romi, Fredrik; Suzuki, Shigeaki; Suzuki, Norihiro; Petzold, Axel; Plant, Gordon T; Gilhus, Nils Erik

    2012-07-01

    Myasthenia gravis (MG) is an autoimmune disease characterized by skeletal muscle weakness mainly caused by acetylcholine receptor antibodies. MG can be divided into generalized and ocular, and into early-onset (<50 years of age) and late-onset (≥50 years of age). Anti-Kv1.4 antibodies targeting α-subunits (Kv1.4) of the voltage-gated potassium K(+) channel occurs frequently among patients with severe MG, accounting for 18% of a Japanese MG population. The aim of this study was to characterize the clinical features and serological associations of anti-Kv1.4 antibodies in a Caucasian MG population with mild and localized MG. Serum samples from 129 Caucasian MG patients with mainly ocular symptoms were tested for the presence of anti-Kv1.4 antibodies and compared to clinical and serological parameters. There were 22 (17%) anti-Kv1.4 antibody-positive patients, most of them women with late-onset MG, and all of them with mild MG. This contrasts to the Japanese anti-Kv1.4 antibody-positive patients who suffered from severe MG with bulbar symptoms, myasthenic crisis, thymoma, myocarditis and prolonged QT time on electrocardiography, despite equal anti-Kv1.4 antibody occurrence in both populations. No other clinical or serological parameters influenced anti-Kv1.4 antibody occurrence.

  14. The Link between Ion Permeation and Inactivation Gating of Kv4 Potassium Channels

    PubMed Central

    Shahidullah, Mohammad; Covarrubias, Manuel

    2003-01-01

    Kv4 potassium channels undergo rapid inactivation but do not seem to exhibit the classical N-type and C-type mechanisms present in other Kv channels. We have previously hypothesized that Kv4 channels preferentially inactivate from the preopen closed state, which involves regions of the channel that contribute to the internal vestibule of the pore. To further test this hypothesis, we have examined the effects of permeant ions on gating of three Kv4 channels (Kv4.1, Kv4.2, and Kv4.3) expressed in Xenopus oocytes. Rb+ is an excellent tool for this purpose because its prolonged residency time in the pore delays K+ channel closing. The data showed that, only when Rb+ carried the current, both channel closing and the development of macroscopic inactivation are slowed (1.5- to 4-fold, relative to the K+ current). Furthermore, macroscopic Rb+ currents were larger than K+ currents (1.2- to 3-fold) as the result of a more stable open state, which increases the maximum open probability. These results demonstrate that pore occupancy can influence inactivation gating in a manner that depends on how channel closing impacts inactivation from the preopen closed state. By examining possible changes in ionic selectivity and the influence of elevating the external K+ concentration, additional experiments did not support the presence of C-type inactivation in Kv4 channels. PMID:12547775

  15. Kv4 Potassium Channels Modulate Hippocampal EPSP-Spike Potentiation and Spatial Memory in Rats

    ERIC Educational Resources Information Center

    Truchet, Bruno; Manrique, Christine; Sreng, Leam; Chaillan, Franck A.; Roman, Francois S.; Mourre, Christiane

    2012-01-01

    Kv4 channels regulate the backpropagation of action potentials (b-AP) and have been implicated in the modulation of long-term potentiation (LTP). Here we showed that blockade of Kv4 channels by the scorpion toxin AmmTX3 impaired reference memory in a radial maze task. In vivo, AmmTX3 intracerebroventricular (i.c.v.) infusion increased and…

  16. The beneficial effect of blocking Kv1.3 in the psoriasiform SCID mouse model.

    PubMed

    Gilhar, Amos; Bergman, Reuven; Assay, Bedia; Ullmann, Yehuda; Etzioni, Amos

    2011-01-01

    The Kv1.3 channel is important in the activation and function of effector memory T cells. Recently, specific blockers of the Kv1.3 channel have been developed as a potential therapeutic option for diverse autoimmune diseases. In psoriatic lesions, most lymphocytes are memory effector T cells. The aim of the present study was to detect the expression of Kv1.3 channels in these cells in psoriatic lesions as well as in human psoriasiform skin grafts using the severe combined immunodeficient (SCID) mouse model. Histological and immunohistochemical staining for Kv1.3 expression and various inflammatory markers was performed in sections obtained from six psoriatic patients and 18 beige-SCID mice with psoriasiform human skin grafts. Six grafted mice were treated with Stichodactyla helianthus neurotoxin (ShK), a known Kv1.3 blocker. The results showed an increased number of Kv1.3+ cells in the psoriatic skin as well as in the psoriasiform skin grafts as compared with normal skin and normal skin grafts. Injections of ShK showed a marked therapeutic effect in three of six psoriasiform skin grafts. A significantly decreased number of Kv1.3+ cells was observed in the responders compared with the control grafts. This pilot study, although performed in a small number of mice, reveals the possible beneficial effect of Kv1.3 blockers in psoriasis patients.

  17. AMIGO-Kv2.1 Potassium Channel Complex Is Associated With Schizophrenia-Related Phenotypes

    PubMed Central

    Peltola, Marjaana A.; Kuja-Panula, Juha; Liuhanen, Johanna; Võikar, Vootele; Piepponen, Petteri; Hiekkalinna, Tero; Taira, Tomi; Lauri, Sari E.; Suvisaari, Jaana; Kulesskaya, Natalia; Paunio, Tiina; Rauvala, Heikki

    2016-01-01

    The enormous variability in electrical properties of neurons is largely affected by a multitude of potassium channel subunits. Kv2.1 is a widely expressed voltage-dependent potassium channel and an important regulator of neuronal excitability. The Kv2.1 auxiliary subunit AMIGO constitutes an integral part of the Kv2.1 channel complex in brain and regulates the activity of the channel. AMIGO and Kv2.1 localize to the distinct somatodendritic clusters at the neuronal plasma membrane. Here we have created and characterized a mouse line lacking the AMIGO gene. Absence of AMIGO clearly reduced the amount of the Kv2.1 channel protein in mouse brain and altered the electrophysiological properties of neurons. These changes were accompanied by behavioral and pharmacological abnormalities reminiscent of those identified in schizophrenia. Concomitantly, we have detected an association of a rare, population-specific polymorphism of KV2.1 (KCNB1) with human schizophrenia in a genetic isolate enriched with schizophrenia. Our study demonstrates the involvement of AMIGO-Kv2.1 channel complex in schizophrenia-related behavioral domains in mice and identifies KV2.1 (KCNB1) as a strong susceptibility gene for schizophrenia spectrum disorders in humans. PMID:26240432

  18. Context view of RyantoRainbow 100kv Transmission Line showing copper wire ...

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

    Context view of Ryan-to-Rainbow 100kv Transmission Line showing copper wire conductors leaving roof of Ryan Powerhouse. View to east - Ryan Hydroelectric Facility, Ryan-to-Rainbow 100 kV Transmission Line, West bank of Missouri River, northeast of Great Falls, Great Falls, Cascade County, MT

  19. Proposed 230-kV Crossover Substation, Big Horn County, Montana: Environmental assessment

    SciTech Connect

    Not Available

    1984-02-01

    Western proposes to construct, operate, and maintain a 230-kV substation northwest of Hardin, Big Horn County, Montana. The proposed Crossover Substation would form an interconnection between Western's Yellowtail-Custer and MPC's Colstrip-Billings 230-kV transmission lines. Impacts and mitigation strategies are discussed.

  20. Fludarabine Inhibits KV1.3 Currents in Human B Lymphocytes

    PubMed Central

    de la Cruz, Alicia; Vera-Zambrano, Alba; Peraza, Diego A.; Valenzuela, Carmen; Zapata, Juan M.; Perez-Chacon, Gema; Gonzalez, Teresa

    2017-01-01

    Fludarabine (F-ara-A) is a purine analog commonly used in the treatment of indolent B cell malignancies that interferes with different aspects of DNA and RNA synthesis. KV1.3 K+ channels are membrane proteins involved in the maintenance of K+ homeostasis and the resting potential of the cell, thus controlling signaling events, proliferation and apoptosis in lymphocytes. Here we show that F-ara-A inhibits KV currents in human B lymphocytes. Our data indicate that KV1.3 is expressed in both BL2 and Dana B cell lines, although total KV1.3 levels were higher in BL2 than in Dana cells. However, KV currents in the plasma membrane were similar in both cell lines and were abrogated by the specific KV1.3 channel inhibitor PAP-1, indicating that KV1.3 accounts for most of the KV currents in these cell lines. F-ara-A, at a concentration (3.5 μM) similar to that achieved in the plasma of fludarabine phosphate-treated patients (3 μM), inhibited KV1.3 currents by 61 ± 6.3% and 52.3 ± 6.3% in BL2 and Dana B cells, respectively. The inhibitory effect of F-ara-A was concentration-dependent and showed an IC50 value of 0.36 ± 0.04 μM and a nH value of 1.07 ± 0.15 in BL2 cells and 0.34 ± 0.13 μM (IC50) and 0.77 ± 0.11 (nH) in Dana cells. F-ara-A inhibition of plasma membrane KV1.3 was observed irrespective of its cytotoxic effect on the cells, BL2 cells being sensitive and Dana cells resistant to F-ara-A cytotoxicity. Interestingly, PAP-1, at concentrations as high as 10 μM, did not affect the viability of BL2 and Dana cells, indicating that blockage of KV1.3 in these cells is not toxic. Finally, F-ara-A had no effect on ectopically expressed KV1.3 channels, suggesting an indirect mechanism of current inhibition. In summary, our results describe the inhibitory effect of F-ara-A on the activity of KV1.3 channel. Although KV1.3 inhibition is not sufficient to induce cell death, further research is needed to determine whether it might still contribute to F-ara-A cytotoxicity

  1. Kv2 channels regulate firing rate in pyramidal neurons from rat sensorimotor cortex

    PubMed Central

    Guan, Dongxu; Armstrong, William E; Foehring, Robert C

    2013-01-01

    The largest outward potassium current in the soma of neocortical pyramidal neurons is due to channels containing Kv2.1 α subunits. These channels have been implicated in cellular responses to seizures and ischaemia, mechanisms for intrinsic plasticity and cell death, and responsiveness to anaesthetic agents. Despite their abundance, knowledge of the function of these delayed rectifier channels has been limited by the lack of specific pharmacological agents. To test for functional roles of Kv2 channels in pyramidal cells from somatosensory or motor cortex of rats (layers 2/3 or 5), we transfected cortical neurons with DNA for a Kv2.1 pore mutant (Kv2.1W365C/Y380T: Kv2.1 DN) in an organotypic culture model to manipulate channel expression. Slices were obtained from rats at postnatal days (P7-P14) and maintained in organotypic culture. We used biolistic methods to transfect neurons with gold ‘bullets’ coated with DNA for the Kv2.1 DN and green fluorescent protein (GFP), GFP alone, or wild type (WT) Kv2.1 plus GFP. Cells that fluoresced green, contained a bullet and responded to positive or negative pressure from the recording pipette were considered to be transfected cells. In each slice, we recorded from a transfected cell and a control non-transfected cell from the same layer and area. Whole-cell voltage-clamp recordings obtained after 3–7 days in culture showed that cells transfected with the Kv2.1 DN had a significant reduction in outward current (∼45% decrease in the total current density measured 200 ms after onset of a voltage step from –78 to –2 mV). Transfection with GFP alone did not affect current amplitude and overexpression of the Kv2.1 WT resulted in greatly increased currents. Current-clamp experiments were used to assess the functional consequences of manipulation of Kv2.1 expression. The results suggest roles for Kv2 channels in controlling membrane potential during the interspike interval (ISI), firing rate, spike frequency adaptation

  2. Asbestos fiber release from the brake pads of overhead industrial cranes

    SciTech Connect

    Spencer, J.W.; Plisko, M.J.; Balzer, J.L.

    1999-06-01

    The purpose of this evaluation was to determine the actual contribution of airborne asbestos fibers to the work environment from the operation of overhead cranes and hoists that use asbestos composition brake pads. The evaluation was conducted in a working manufacturing facility. Other potential sources of asbestos were accounted for by visual inspection and background air monitoring. An overhead crane assembly comprised of a trolley and two hoists was employed for this study. The crane was operated for two consecutive eight-hour shifts representative of a heavy-duty cycle. Forty-four personal and area air samples were collected during the assessment. Asbestos fibers were analyzed for by phase contrast (NIOSH 7400), and transmission electron (NIOSH 7402) microscopy methods. Eight-hour time-weighted average (TWA) asbestos fiber concentrations ranges from <0.005 to 0.011 fibers/cc (PCM), and <0.0026 to <0.0094f/cc (TEM). There were no asbestos fibers detected by the TEM method from air samples collected during the operation of the cranes.

  3. A combined study of heat and mass transfer in an infant incubator with an overhead screen.

    PubMed

    Ginalski, Maciej K; Nowak, Andrzej J; Wrobel, Luiz C

    2007-06-01

    The main objective of this study is to investigate the major physical processes taking place inside an infant incubator, before and after modifications have been made to its interior chamber. The modification involves the addition of an overhead screen to decrease radiation heat losses from the infant placed inside the incubator. The present study investigates the effect of these modifications on the convective heat flux from the infant's body to the surrounding environment inside the incubator. A combined analysis of airflow and heat transfer due to conduction, convection, radiation and evaporation has been performed, in order to calculate the temperature and velocity fields inside the incubator before and after the design modification. Due to the geometrical complexity of the model, computer-aided design (CAD) applications were used to generate a computer-based model. All numerical calculations have been performed using the commercial computational fluid dynamics (CFD) package FLUENT, together with in-house routines used for managing purposes and user-defined functions (UDFs) which extend the basic solver capabilities. Numerical calculations have been performed for three different air inlet temperatures: 32, 34 and 36 degrees C. The study shows a decrease of the radiative and convective heat losses when the overhead screen is present. The results obtained were numerically verified as well as compared with results available in the literature from investigations of dry heat losses from infant manikins.

  4. Prevention of shoulder injuries in overhead athletes: a science-based approach

    PubMed Central

    Cools, Ann M.; Johansson, Fredrik R.; Borms, Dorien; Maenhout, Annelies

    2015-01-01

    The shoulder is at high risk for injury during overhead sports, in particular in throwing or hitting activities, such as baseball, tennis, handball, and volleyball. In order to create a scientific basis for the prevention of recurrent injuries in overhead athletes, four steps need to be undertaken: (1) risk factors for injury and re-injury need to be defined; (2) established risk factors may be used as return-to-play criteria, with cut-off values based on normative databases; (3) these variables need to be measured using reliable, valid assessment tools and procedures; and (4) preventative training programs need to be designed and implemented into the training program of the athlete in order to prevent re-injury. In general, three risk factors have been defined that may form the basis for recommendations for the prevention of recurrent injury and return to play after injury: glenohumeral internal-rotation deficit (GIRD); rotator cuff strength, in particular the strength of the external rotators; and scapular dyskinesis, in particular scapular position and strength. PMID:26537804

  5. Treatment of the ulnar nerve for overhead throwing athletes undergoing ulnar collateral ligament reconstruction

    PubMed Central

    Conti, Matthew S; Camp, Christopher L; Elattrache, Neal S; Altchek, David W; Dines, Joshua S

    2016-01-01

    Ulnar nerve (UN) injuries are a common complaint amongst overhead athletes. The UN is strained during periods of extreme valgus stress at the elbow, especially in the late-cocking and early acceleration phases of throwing. Although early ulnar collateral ligament (UCL) reconstruction techniques frequently included routine submuscular UN transposition, this is becoming less common with more modern techniques. We review the recent literature on the sites of UN compression, techniques to evaluate the UN nerve, and treatment of UN pathology in the overhead athlete. We also discuss our preferred techniques for selective decompression and anterior transposition of the UN when indicated. More recent studies support the use of UN transpositions only when there are specific preoperative symptoms. Athletes with isolated ulnar neuropathy are increasingly being treated with subcutaneous anterior transposition of the nerve rather than submuscular transposition. When ulnar neuropathy occurs with UCL insufficiency, adoption of the muscle-splitting approach for UCL reconstructions, as well as using a subcutaneous UN transposition have led to fewer postoperative complications and improved outcomes. Prudent handling of the UN in addition to appropriate surgical technique can lead to a high percentage of athletes who return to competitive sports following surgery for ulnar neuropathy. PMID:27795946

  6. Error tracking control for underactuated overhead cranes against arbitrary initial payload swing angles

    NASA Astrophysics Data System (ADS)

    Zhang, Menghua; Ma, Xin; Rong, Xuewen; Tian, Xincheng; Li, Yibin

    2017-02-01

    This paper exploits an error tracking control method for overhead crane systems for which the error trajectories for the trolley and the payload swing can be pre-specified. The proposed method does not require that the initial payload swing angle remains zero, whereas this requirement is usually assumed in conventional methods. The significant feature of the proposed method is its superior control performance as well as its strong robustness over different or uncertain rope lengths, payload masses, desired positions, initial payload swing angles, and external disturbances. Owing to the same attenuation behavior, the desired error trajectory for the trolley for each traveling distance is not needed to be reset, which is easy to implement in practical applications. By converting the error tracking overhead crane dynamics to the objective system, we obtain the error tracking control law for arbitrary initial payload swing angles. Lyapunov techniques and LaSalle's invariance theorem are utilized to prove the convergence and stability of the closed-loop system. Simulation and experimental results are illustrated to validate the superior performance of the proposed error tracking control method.

  7. Measurement and Modeling of Job Stress of Electric Overhead Traveling Crane Operators

    PubMed Central

    Krishna, Obilisetty B.; Maiti, Jhareswar; Ray, Pradip K.; Samanta, Biswajit; Mandal, Saptarshi; Sarkar, Sobhan

    2015-01-01

    Background In this study, the measurement of job stress of electric overhead traveling crane operators and quantification of the effects of operator and workplace characteristics on job stress were assessed. Methods Job stress was measured on five subscales: employee empowerment, role overload, role ambiguity, rule violation, and job hazard. The characteristics of the operators that were studied were age, experience, body weight, and body height. The workplace characteristics considered were hours of exposure, cabin type, cabin feature, and crane height. The proposed methodology included administration of a questionnaire survey to 76 electric overhead traveling crane operators followed by analysis using analysis of variance and a classification and regression tree. Results The key findings were: (1) the five subscales can be used to measure job stress; (2) employee empowerment was the most significant factor followed by the role overload; (3) workplace characteristics contributed more towards job stress than operator's characteristics; and (4) of the workplace characteristics, crane height was the major contributor. Conclusion The issues related to crane height and cabin feature can be fixed by providing engineering or foolproof solutions than relying on interventions related to the demographic factors. PMID:26929839

  8. Ultra-scale vehicle tracking in low spatial resolution and low frame-rate overhead video

    NASA Astrophysics Data System (ADS)

    Carrano, Carmen J.

    2009-08-01

    Overhead persistent surveillance systems are becoming more capable at acquiring wide-field image sequences for long time-spans. The need to exploit this data is becoming ever greater. The ability to track a single vehicle of interest or to track all the observable vehicles, which may number in the thousands, over large, cluttered regions while they persist in the imagery either in real-time or quickly on-demand is very desirable. With this ability we can begin to answer a number of interesting questions such as, what are normal traffic patterns in a particular region or where did that truck come from? There are many challenges associated with processing this type of data, some of which we will address in the paper. Wide-field image sequences are very large with many thousands of pixels on a side and are characterized by lower resolutions (e.g. worse than 0.5 meters/pixel) and lower frame rates (e.g. a few Hz or less). The objects in the scenery can vary in size, density, and contrast with respect to the background. At the same time the background scenery provides a number of clutter sources both man-made and natural. We describe our current implementation of an ultrascale capable multiple-vehicle tracking algorithm for overhead persistent surveillance imagery as well as discuss the tracking and timing performance of the currently implemented algorithm which is aimed at utilizing grayscale electrooptical image sequences alone for the track segment generation.

  9. "Mtrack 2.0": An ultra-scale tracking algorithm for low-resolution overhead imagery

    SciTech Connect

    Carrano, C J

    2008-09-26

    Overhead persistent surveillance systems are becoming more capable at acquiring wide-field image sequences for long time-spans. The need to exploit this data is becoming ever greater. The ability to track a single vehicle of interest or to track all the observable vehicles, which may number in the thousands, over large, cluttered regions while they persist in the imagery is very desirable. Typically, this imagery has many thousands of pixels on a side and is characterized by lower resolutions (e.g. {approx}0.5 meters/pixel to {approx}2.0 meters/pixel) and lower frame rates (e.g. {approx} sub-Hz to several Hz). We describe our ultra-scale capable implementation of a multiple-vehicle tracking algorithm for overhead persistent surveillance imagery. This work builds upon an earlier report, where now the algorithm has been modified for improved performance and has been substantially improved to handle much larger datasets in a much shorter time.

  10. Study of Corrosion Resistance Improvement by Metallic Coating for Overhead Transmission Line Conductor

    NASA Astrophysics Data System (ADS)

    Isozaki, Masanori; Adachi, Kouichi; Hita, Takanori; Asano, Yuji

    Applying anti-corrosion grease and aluminum clad steel (AC) wires to ACSR has adopted as general methods to prevent overhead transmission line conductors and/or wires from corrosion. However, there are some cases that ineffectiveness of those means are reported on some transmission lines passing through acid atmosphere in the vicinity of a factory exhausting acid smoke. The feature of the corrosion caused by acid atmosphere is to show a higher speed in its progressing as well known. As means against such acid corrosion, application of high purity aluminum, selective removal of inter-metallic compound in aluminum and plastic coating wires has been reported before, and each has both of advantage and disadvantage actually. In the former letter, we reported the new type of anti-corrosion grease that shows an excellent property against acid atmosphere as well as in a salty circumstance. Here presents a new type of anti-corrosion technology of applying high corrosion resistance aluminum alloy or zinc coatings on each component wires of a conductor that we succeed in developing through a serial study of anti-corrosion methods on overhead transmission lines.

  11. SMAC: A soft MAC to reduce control overhead and latency in CDMA-based AMI networks

    DOE PAGES

    Garlapati, Shravan; Kuruganti, Teja; Buehrer, Michael R.; ...

    2015-10-26

    The utilization of state-of-the-art 3G cellular CDMA technologies in a utility owned AMI network results in a large amount of control traffic relative to data traffic, increases the average packet delay and hence are not an appropriate choice for smart grid distribution applications. Like the CDG, we consider a utility owned cellular like CDMA network for smart grid distribution applications and classify the distribution smart grid data as scheduled data and random data. Also, we propose SMAC protocol, which changes its mode of operation based on the type of the data being collected to reduce the data collection latency andmore » control overhead when compared to 3G cellular CDMA2000 MAC. The reduction in the data collection latency and control overhead aids in increasing the number of smart meters served by a base station within the periodic data collection interval, which further reduces the number of base stations needed by a utility or reduces the bandwidth needed to collect data from all the smart meters. The reduction in the number of base stations and/or the reduction in the data transmission bandwidth reduces the CAPital EXpenditure (CAPEX) and OPerational EXpenditure (OPEX) of the AMI network. Finally, the proposed SMAC protocol is analyzed using markov chain, analytical expressions for average throughput and average packet delay are derived, and simulation results are also provided to verify the analysis.« less

  12. SMAC: A soft MAC to reduce control overhead and latency in CDMA-based AMI networks

    SciTech Connect

    Garlapati, Shravan; Kuruganti, Teja; Buehrer, Michael R.; Reed, Jeffrey H.

    2015-10-26

    The utilization of state-of-the-art 3G cellular CDMA technologies in a utility owned AMI network results in a large amount of control traffic relative to data traffic, increases the average packet delay and hence are not an appropriate choice for smart grid distribution applications. Like the CDG, we consider a utility owned cellular like CDMA network for smart grid distribution applications and classify the distribution smart grid data as scheduled data and random data. Also, we propose SMAC protocol, which changes its mode of operation based on the type of the data being collected to reduce the data collection latency and control overhead when compared to 3G cellular CDMA2000 MAC. The reduction in the data collection latency and control overhead aids in increasing the number of smart meters served by a base station within the periodic data collection interval, which further reduces the number of base stations needed by a utility or reduces the bandwidth needed to collect data from all the smart meters. The reduction in the number of base stations and/or the reduction in the data transmission bandwidth reduces the CAPital EXpenditure (CAPEX) and OPerational EXpenditure (OPEX) of the AMI network. Finally, the proposed SMAC protocol is analyzed using markov chain, analytical expressions for average throughput and average packet delay are derived, and simulation results are also provided to verify the analysis.

  13. Effect of Overhead Ground Wire Installing under Distribution Lines on Surge Arrester Failures

    NASA Astrophysics Data System (ADS)

    Sugimoto, Hitoshi

    Distribution surge arresters are often damaged by lightning strokes, in particular, winter lightning. An overhead ground wire (OGW) is one of effective measures against surge arrester failures. However, adding the conventional OGW to existing overhead power distribution lines needs the power interruption for construction as well as high costs because of installing them above phase conductors. Experimental results show that a covered conductor for distribution lines is more difficult to attract lightning than a bare conductor. Moreover, lightning strokes to distribution pole heads occupied over 90% of all lightning strokes in the observation result of lightning strokes to actual distribution lines without the conventional OGW, and lightning strokes to power lines were hardly observed. These results indicate that the pole heads shield the power lines from direct lightning strokes. Therefore the author studies the application of an OGW under the distribution lines (UGW) for reducing surge arrester failures. The lightning performance of the UGW is estimated by the Electro-Magnetic Transients Program (EMTP) and its effectiveness is demonstrated. The measure is expected to cut costs of construction and maintenance for lightning protection.

  14. The KCNE Tango - How KCNE1 Interacts with Kv7.1.

    PubMed

    Wrobel, Eva; Tapken, Daniel; Seebohm, Guiscard

    2012-01-01

    The classical tango is a dance characterized by a 2/4 or 4/4 rhythm in which the partners dance in a coordinated way, allowing dynamic contact. There is a surprising similarity between the tango and how KCNE β-subunits "dance" to the fast rhythm of the cell with their partners from the Kv channel family. The five KCNE β-subunits interact with several members of the Kv channels, thereby modifying channel gating via the interaction of their single transmembrane-spanning segment, the extracellular amino terminus, and/or the intracellular carboxy terminus with the Kv α-subunit. Best studied is the molecular basis of interactions between KCNE1 and Kv7.1, which, together, supposedly form the native cardiac I(Ks) channel. Here we review the current knowledge about functional and molecular interactions of KCNE1 with Kv7.1 and try to summarize and interpret the tango of the KCNEs.

  15. The KCNE Tango – How KCNE1 Interacts with Kv7.1

    PubMed Central

    Wrobel, Eva; Tapken, Daniel; Seebohm, Guiscard

    2012-01-01

    The classical tango is a dance characterized by a 2/4 or 4/4 rhythm in which the partners dance in a coordinated way, allowing dynamic contact. There is a surprising similarity between the tango and how KCNE β-subunits “dance” to the fast rhythm of the cell with their partners from the Kv channel family. The five KCNE β-subunits interact with several members of the Kv channels, thereby modifying channel gating via the interaction of their single transmembrane-spanning segment, the extracellular amino terminus, and/or the intracellular carboxy terminus with the Kv α-subunit. Best studied is the molecular basis of interactions between KCNE1 and Kv7.1, which, together, supposedly form the native cardiac IKs channel. Here we review the current knowledge about functional and molecular interactions of KCNE1 with Kv7.1 and try to summarize and interpret the tango of the KCNEs. PMID:22876232

  16. Kv7.2 regulates the function of peripheral sensory neurons

    PubMed Central

    King, Chih H.; Lancaster, Eric; Salomon, Daniela; Peles, Elior; Scherer, Steven S.

    2014-01-01

    The Kv7 (KCNQ) family of voltage-gated K+ channels regulates cellular excitability. The functional role of Kv7.2 has been hampered by the lack of a viable Kcnq2-null animal model. In this study, we generated homozygous Kcnq2-null sensory neurons using the Cre-Lox system; in these mice, Kv7.2 expression is absent in the peripheral sensory neurons, whereas the expression of other molecular components of nodes (including Kv7.3), paranodes, and juxtaparanodes is not altered. The conditional Kcnq2-null animals exhibit normal motor performance, but have increased thermal hyperalgesia and mechanical allodynia. Whole cell patch recording technique demonstrates that Kcnq2-null sensory neurons have increased excitability and reduced spike frequency adaptation. Taken together, our results suggest that the loss of Kv7.2 activity increases the excitability of primary sensory neurons. PMID:24687876

  17. The effect of overhead target on the lower limb biomechanics during a vertical drop jump test in elite female athletes.

    PubMed

    Mok, K-M; Bahr, R; Krosshaug, T

    2017-02-01

    The purpose of the study was to investigate the effect of an overhead target on the jump height and lower limb biomechanics in all three planes of motion in a vertical drop jump (VDJ) task among elite female handball and football (soccer) players. The hypothesis was that adding an overhead target to the VDJ task improves jump height, increases joint loading, and decreases frontal plane knee control. Five hundred and twenty-three female handball and football players (mean ± SD: 21 ± 4 years, 168 ± 6 cm, 65 ± 8 kg) completed the test. The overhead target increased jumping height by 5.8%. Furthermore, the overhead target led to statistically significant changes in many of the lower limb biomechanical variables examined. However, all the changes in kinematics and kinetics were clinically insignificant, as indicated by the small effect sizes. Strong to moderate positive Spearman's rank correlations were found between the two conditions. Therefore, an overhead target is unlikely to increase the range of responses in biomechanical variables in elite female handball and football athletes.

  18. Dysregulation of Kv3.4 channels in dorsal root ganglia following spinal cord injury.

    PubMed

    Ritter, David M; Zemel, Benjamin M; Hala, Tamara J; O'Leary, Michael E; Lepore, Angelo C; Covarrubias, Manuel

    2015-01-21

    Spinal cord injury (SCI) patients develop chronic pain involving poorly understood central and peripheral mechanisms. Because dysregulation of the voltage-gated Kv3.4 channel has been implicated in the hyperexcitable state of dorsal root ganglion (DRG) neurons following direct injury of sensory nerves, we asked whether such a dysregulation also plays a role in SCI. Kv3.4 channels are expressed in DRG neurons, where they help regulate action potential (AP) repolarization in a manner that depends on the modulation of inactivation by protein kinase C (PKC)-dependent phosphorylation of the channel's inactivation domain. Here, we report that, 2 weeks after cervical hemicontusion SCI, injured rats exhibit contralateral hypersensitivity to stimuli accompanied by accentuated repetitive spiking in putative DRG nociceptors. Also in these neurons at 1 week after laminectomy and SCI, Kv3.4 channel inactivation is impaired compared with naive nonsurgical controls. At 2-6 weeks after laminectomy, however, Kv3.4 channel inactivation returns to naive levels. Conversely, Kv3.4 currents at 2-6 weeks post-SCI are downregulated and remain slow-inactivating. Immunohistochemistry indicated that downregulation mainly resulted from decreased surface expression of the Kv3.4 channel, as whole-DRG-protein and single-cell mRNA transcript levels did not change. Furthermore, consistent with Kv3.4 channel dysregulation, PKC activation failed to shorten the AP duration of small-diameter DRG neurons. Finally, re-expressing synthetic Kv3.4 currents under dynamic clamp conditions dampened repetitive spiking in the neurons from SCI rats. These results suggest a novel peripheral mechanism of post-SCI pain sensitization implicating Kv3.4 channel dysregulation and potential Kv3.4-based therapeutic interventions.

  19. Kinesin I transports tetramerized Kv3 channels through the axon initial segment via direct binding.

    PubMed

    Xu, Mingxuan; Gu, Yuanzheng; Barry, Joshua; Gu, Chen

    2010-11-24

    Precise targeting of various voltage-gated ion channels to proper membrane domains is crucial for their distinct roles in neuronal excitability and synaptic transmission. How each channel protein is transported within the cytoplasm is poorly understood. Here, we report that KIF5/kinesin I transports Kv3.1 voltage-gated K(+) (Kv) channels through the axon initial segment (AIS) via direct binding. First, we have identified a novel interaction between Kv3.1 and KIF5, confirmed by immunoprecipitation from mouse brain lysates and by pull-down assays with exogenously expressed proteins. The interaction is mediated by a direct binding between the Kv3.1 N-terminal T1 domain and a conserved region in KIF5 tail domains, in which proper T1 tetramerization is crucial. Overexpression of this region of KIF5B markedly reduces axonal levels of Kv3.1bHA. In mature hippocampal neurons, endogenous Kv3.1b and KIF5 colocalize. Suppressing the endogenous KIF5B level by RNA interference significantly reduces the Kv3.1b axonal level. Furthermore, mutating the Zn(2+)-binding site within T1 markedly decreases channel axonal targeting and forward trafficking, likely through disrupting T1 tetramerization and hence eliminating the binding to KIF5 tail. The mutation also alters channel activity. Interestingly, coexpression of the YFP (yellow fluorescent protein)-tagged KIF5B assists dendritic Kv3.1a and even mutants with a faulty axonal targeting motif to penetrate the AIS. Finally, fluorescently tagged Kv3.1 channels colocalize and comove with KIF5B along axons revealed by two-color time-lapse imaging. Our findings suggest that the binding to KIF5 ensures properly assembled and functioning Kv3.1 channels to be transported into axons.

  20. Nuclear localization and functional characteristics of voltage-gated potassium channel Kv1.3.

    PubMed

    Jang, Soo Hwa; Byun, Jun Kyu; Jeon, Won-Il; Choi, Seon Young; Park, Jin; Lee, Bo Hyung; Yang, Ji Eun; Park, Jin Bong; O'Grady, Scott M; Kim, Dae-Yong; Ryu, Pan Dong; Joo, Sang-Woo; Lee, So Yeong

    2015-05-15

    It is widely known that ion channels are expressed in the plasma membrane. However, a few studies have suggested that several ion channels including voltage-gated K(+) (Kv) channels also exist in intracellular organelles where they are involved in the biochemical events associated with cell signaling. In the present study, Western blot analysis using fractionated protein clearly indicates that Kv1.3 channels are expressed in the nuclei of MCF7, A549, and SNU-484 cancer cells and human brain tissues. In addition, Kv1.3 is located in the plasma membrane and the nucleus of Jurkat T cells. Nuclear membrane hyperpolarization after treatment with margatoxin (MgTX), a specific blocker of Kv1.3 channels, provides evidence for functional channels at the nuclear membrane of A549 cells. MgTX-induced hyperpolarization is abolished in the nuclei of Kv1.3 silenced cells, and the effects of MgTX are dependent on the magnitude of the K(+) gradient across the nuclear membrane. Selective Kv1.3 blockers induce the phosphorylation of cAMP response element-binding protein (CREB) and c-Fos activation. Moreover, Kv1.3 is shown to form a complex with the upstream binding factor 1 in the nucleus. Chromatin immunoprecipitation assay reveals that Sp1 transcription factor is directly bound to the promoter region of the Kv1.3 gene, and the Sp1 regulates Kv1.3 expression in the nucleus of A549 cells. These results demonstrate that Kv1.3 channels are primarily localized in the nucleus of several types of cancer cells and human brain tissues where they are capable of regulating nuclear membrane potential and activation of transcription factors, such as phosphorylated CREB and c-Fos.

  1. Retigabine holds KV7 channels open and stabilizes the resting potential

    PubMed Central

    Corbin-Leftwich, Aaron; Mossadeq, Sayeed M.; Ha, Junghoon; Ruchala, Iwona; Le, Audrey Han Ngoc

    2016-01-01

    The anticonvulsant Retigabine is a KV7 channel agonist used to treat hyperexcitability disorders in humans. Retigabine shifts the voltage dependence for activation of the heteromeric KV7.2/KV7.3 channel to more negative potentials, thus facilitating activation. Although the molecular mechanism underlying Retigabine’s action remains unknown, previous studies have identified the pore region of KV7 channels as the drug’s target. This suggested that the Retigabine-induced shift in voltage dependence likely derives from the stabilization of the pore domain in an open (conducting) conformation. Testing this idea, we show that the heteromeric KV7.2/KV7.3 channel has at least two open states, which we named O1 and O2, with O2 being more stable. The O1 state was reached after short membrane depolarizations, whereas O2 was reached after prolonged depolarization or during steady state at the typical neuronal resting potentials. We also found that activation and deactivation seem to follow distinct pathways, suggesting that the KV7.2/KV7.3 channel activity displays hysteresis. As for the action of Retigabine, we discovered that this agonist discriminates between open states, preferentially acting on the O2 state and further stabilizing it. Based on these findings, we proposed a novel mechanism for the therapeutic effect of Retigabine whereby this drug reduces excitability by enhancing the resting potential open state stability of KV7.2/KV7.3 channels. To address this hypothesis, we used a model for action potential (AP) in Xenopus laevis oocytes and found that the resting membrane potential became more negative as a function of Retigabine concentration, whereas the threshold potential for AP firing remained unaltered. PMID:26880756

  2. Kinesin I transports tetramerized Kv3 channels through the axon initial segment via direct binding

    PubMed Central

    Xu, Mingxuan; Gu, Yuanzheng; Barry, Joshua; Gu, Chen

    2010-01-01

    Precise targeting of various voltage-gated ion channels to proper membrane domains is crucial for their distinct roles in neuronal excitability and synaptic transmission. How each channel protein is transported within the cytoplasm is poorly understood. Here we report that KIF5/kinesin I transports Kv3.1 voltage-gated K+ (Kv) channels through the axon initial segment (AIS) via direct binding. First, we have identified a novel interaction between Kv3.1 and KIF5, confirmed by immunoprecipitation from mouse brain lysates and by pull down assays with exogenously-expressed proteins. The interaction is mediated by a direct binding between the Kv3.1 N-terminal T1 domain and a conserved region in KIF5 tail domains, in which proper T1 tetramerization is crucial. Over-expression of this region of KIF5B markedly reduces axonal levels of Kv3.1bHA. In mature hippocampal neurons, endogenous Kv3.1b and KIF5 colocalize. Suppressing the endogenous KIF5B level by siRNA significantly reduces the Kv3.1b axonal level. Furthermore, mutating the Zn2+-binding site within T1 markedly decreases channel axonal targeting and forward trafficking, likely through disrupting T1 tetramerization and hence eliminating the binding to KIF5 tail. The mutation also alters channel activity. Interestingly, co-expression of the YFP-tagged KIF5B assists dendritic Kv3.1a and even mutants with a faulty axonal targeting motif to penetrate the AIS. Finally, fluorescently tagged Kv3.1 channels co-localize and co-move with KIF5B along axons revealed by two-color time-lapse imaging. Our findings suggest that the binding to KIF5 ensures properly assembled and functioning Kv3.1 channels to be transported into axons. PMID:21106837

  3. Dysregulation of Kv3.4 Channels in Dorsal Root Ganglia Following Spinal Cord Injury

    PubMed Central

    Ritter, David M.; Zemel, Benjamin M.; Hala, Tamara J.; O'Leary, Michael E.; Lepore, Angelo C.

    2015-01-01

    Spinal cord injury (SCI) patients develop chronic pain involving poorly understood central and peripheral mechanisms. Because dysregulation of the voltage-gated Kv3.4 channel has been implicated in the hyperexcitable state of dorsal root ganglion (DRG) neurons following direct injury of sensory nerves, we asked whether such a dysregulation also plays a role in SCI. Kv3.4 channels are expressed in DRG neurons, where they help regulate action potential (AP) repolarization in a manner that depends on the modulation of inactivation by protein kinase C (PKC)-dependent phosphorylation of the channel's inactivation domain. Here, we report that, 2 weeks after cervical hemicontusion SCI, injured rats exhibit contralateral hypersensitivity to stimuli accompanied by accentuated repetitive spiking in putative DRG nociceptors. Also in these neurons at 1 week after laminectomy and SCI, Kv3.4 channel inactivation is impaired compared with naive nonsurgical controls. At 2–6 weeks after laminectomy, however, Kv3.4 channel inactivation returns to naive levels. Conversely, Kv3.4 currents at 2–6 weeks post-SCI are downregulated and remain slow-inactivating. Immunohistochemistry indicated that downregulation mainly resulted from decreased surface expression of the Kv3.4 channel, as whole-DRG-protein and single-cell mRNA transcript levels did not change. Furthermore, consistent with Kv3.4 channel dysregulation, PKC activation failed to shorten the AP duration of small-diameter DRG neurons. Finally, re-expressing synthetic Kv3.4 currents under dynamic clamp conditions dampened repetitive spiking in the neurons from SCI rats. These results suggest a novel peripheral mechanism of post-SCI pain sensitization implicating Kv3.4 channel dysregulation and potential Kv3.4-based therapeutic interventions. PMID:25609640

  4. Nuclear Localization and Functional Characteristics of Voltage-gated Potassium Channel Kv1.3*

    PubMed Central

    Jang, Soo Hwa; Byun, Jun Kyu; Jeon, Won-Il; Choi, Seon Young; Park, Jin; Lee, Bo Hyung; Yang, Ji Eun; Park, Jin Bong; O'Grady, Scott M.; Kim, Dae-Yong; Ryu, Pan Dong; Joo, Sang-Woo; Lee, So Yeong

    2015-01-01

    It is widely known that ion channels are expressed in the plasma membrane. However, a few studies have suggested that several ion channels including voltage-gated K+ (Kv) channels also exist in intracellular organelles where they are involved in the biochemical events associated with cell signaling. In the present study, Western blot analysis using fractionated protein clearly indicates that Kv1.3 channels are expressed in the nuclei of MCF7, A549, and SNU-484 cancer cells and human brain tissues. In addition, Kv1.3 is located in the plasma membrane and the nucleus of Jurkat T cells. Nuclear membrane hyperpolarization after treatment with margatoxin (MgTX), a specific blocker of Kv1.3 channels, provides evidence for functional channels at the nuclear membrane of A549 cells. MgTX-induced hyperpolarization is abolished in the nuclei of Kv1.3 silenced cells, and the effects of MgTX are dependent on the magnitude of the K+ gradient across the nuclear membrane. Selective Kv1.3 blockers induce the phosphorylation of cAMP response element-binding protein (CREB) and c-Fos activation. Moreover, Kv1.3 is shown to form a complex with the upstream binding factor 1 in the nucleus. Chromatin immunoprecipitation assay reveals that Sp1 transcription factor is directly bound to the promoter region of the Kv1.3 gene, and the Sp1 regulates Kv1.3 expression in the nucleus of A549 cells. These results demonstrate that Kv1.3 channels are primarily localized in the nucleus of several types of cancer cells and human brain tissues where they are capable of regulating nuclear membrane potential and activation of transcription factors, such as phosphorylated CREB and c-Fos. PMID:25829491

  5. 75 FR 75170 - Minnkota Power Cooperative, Inc.: Bemidji to Grand Rapids 230 kV Transmission Line Project

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-02

    ... Rural Utilities Service Minnkota Power Cooperative, Inc.: Bemidji to Grand Rapids 230 kV Transmission... to Grand Rapids 230 kV Transmission Line Project (Project) in Beltrami, Hubbard, Itasca, and Cass... construct the 230 kilovolt (kV) transmission line between the Wilton Substation near Bemidji, Minnesota...

  6. Transient Hippocampal Down-Regulation of Kv1.1 Subunit mRNA during Associative Learning in Rats

    ERIC Educational Resources Information Center

    Kourrich, Said; Manrique, Christine; Salin, Pascal; Mourre, Christiane

    2005-01-01

    Voltage-gated potassium channels (Kv) are critically involved in learning and memory processes. It is not known, however, whether the expression of the Kv1.1 subunit, constituting Kv1 channels, can be specifically regulated in brain areas important for learning and memory processing. Radioactive in situ hybridization was used to evaluate the…

  7. KV7 channels are involved in hypoxia-induced vasodilatation of porcine coronary arteries

    PubMed Central

    Hedegaard, E R; Nielsen, B D; Kun, A; Hughes, A D; Krøigaard, C; Mogensen, S; Matchkov, V V; Fröbert, O; Simonsen, U

    2014-01-01

    BACKGROUND AND PURPOSE Hypoxia causes vasodilatation of coronary arteries, but the underlying mechanisms are poorly understood. We hypothesized that hypoxia reduces intracellular Ca2+ concentration ([Ca2+]i) by opening of K channels and release of H2S. EXPERIMENTAL APPROACH Porcine coronary arteries without endothelium were mounted for measurement of isometric tension and [Ca2+]i, and the expression of voltage-gated K channels KV7 channels (encoded by KCNQ genes) and large-conductance calcium-activated K channels (KCa1.1) was examined. Voltage clamp assessed the role of KV7 channels in hypoxia. KEY RESULTS Gradual reduction of oxygen concentration from 95 to 1% dilated the precontracted coronary arteries and this was associated with reduced [Ca2+]i in PGF2α (10 μM)-contracted arteries whereas no fall in [Ca2+]i was observed in 30 mM K-contracted arteries. Blockers of ATP-sensitive voltage-gated potassium channels and KCa1.1 inhibited hypoxia-induced dilatation in PGF2α-contracted arteries; this inhibition was more marked in the presence of the Kv7 channel blockers, XE991 and linopirdine, while a KV7.1 blocker, failed to change hypoxic vasodilatation. XE991 also inhibited H2S- and adenosine-induced vasodilatation. PCR revealed the expression of KV7.1, KV7.4, KV7.5 and KCa1.1 channels, and KCa1.1, KV7.4 and KV7.5 were also identified by immunoblotting. Voltage clamp studies showed the XE991-sensitive current was more marked in hypoxic conditions. CONCLUSION The KV7.4 and KV7.5 channels, which we identified in the coronary arteries, appear to have a major role in hypoxia-induced vasodilatation. The voltage clamp results further support the involvement of KV7 channels in this vasodilatation. Activation of these KV7 channels may be induced by H2S and adenosine. PMID:24111896

  8. Modeling-independent elucidation of inactivation pathways in recombinant and native A-type Kv channels.

    PubMed

    Fineberg, Jeffrey D; Ritter, David M; Covarrubias, Manuel

    2012-11-01

    A-type voltage-gated K(+) (Kv) channels self-regulate their activity by inactivating directly from the open state (open-state inactivation [OSI]) or by inactivating before they open (closed-state inactivation [CSI]). To determine the inactivation pathways, it is often necessary to apply several pulse protocols, pore blockers, single-channel recording, and kinetic modeling. However, intrinsic hurdles may preclude the standardized application of these methods. Here, we implemented a simple method inspired by earlier studies of Na(+) channels to analyze macroscopic inactivation and conclusively deduce the pathways of inactivation of recombinant and native A-type Kv channels. We investigated two distinct A-type Kv channels expressed heterologously (Kv3.4 and Kv4.2 with accessory subunits) and their native counterparts in dorsal root ganglion and cerebellar granule neurons. This approach applies two conventional pulse protocols to examine inactivation induced by (a) a simple step (single-pulse inactivation) and (b) a conditioning step (double-pulse inactivation). Consistent with OSI, the rate of Kv3.4 inactivation (i.e., the negative first derivative of double-pulse inactivation) precisely superimposes on the profile of the Kv3.4 current evoked by a single pulse because the channels must open to inactivate. In contrast, the rate of Kv4.2 inactivation is asynchronous, already changing at earlier times relative to the profile of the Kv4.2 current evoked by a single pulse. Thus, Kv4.2 inactivation occurs uncoupled from channel opening, indicating CSI. Furthermore, the inactivation time constant versus voltage relation of Kv3.4 decreases monotonically with depolarization and levels off, whereas that of Kv4.2 exhibits a J-shape profile. We also manipulated the inactivation phenotype by changing the subunit composition and show how CSI and CSI combined with OSI might affect spiking properties in a full computational model of the hippocampal CA1 neuron. This work unambiguously

  9. SU-E-I-23: A General KV Constrained Optimization of CNR for CT Abdominal Imaging

    SciTech Connect

    Weir, V; Zhang, J

    2015-06-15

    Purpose: While Tube current modulation has been well accepted for CT dose reduction, kV adjusting in clinical settings is still at its early stage. This is mainly due to the limited kV options of most current CT scanners. kV adjusting can potentially reduce radiation dose and optimize image quality. This study is to optimize CT abdomen imaging acquisition based on the assumption of a continuous kV, with the goal to provide the best contrast to noise ratio (CNR). Methods: For a given dose (CTDIvol) level, the CNRs at different kV and pitches were measured with an ACR GAMMEX phantom. The phantom was scanned in a Siemens Sensation 64 scanner and a GE VCT 64 scanner. A constrained mathematical optimization was used to find the kV which led to the highest CNR for the anatomy and pitch setting. Parametric equations were obtained from polynomial fitting of plots of kVs vs CNRs. A suitable constraint region for optimization was chosen. Subsequent optimization yielded a peak CNR at a particular kV for different collimations and pitch setting. Results: The constrained mathematical optimization approach yields kV of 114.83 and 113.46, with CNRs of 1.27 and 1.11 at the pitch of 1.2 and 1.4, respectively, for the Siemens Sensation 64 scanner with the collimation of 32 x 0.625mm. An optimized kV of 134.25 and 1.51 CNR is obtained for a GE VCT 64 slice scanner with a collimation of 32 x 0.625mm and a pitch of 0.969. At 0.516 pitch and 32 x 0.625 mm an optimized kV of 133.75 and a CNR of 1.14 was found for the GE VCT 64 slice scanner. Conclusion: CNR in CT image acquisition can be further optimized with a continuous kV option instead of current discrete or fixed kV settings. A continuous kV option is a key for individualized CT protocols.

  10. Mitochondrial Ultrastructure and Glucose Signaling Pathways Attributed to the Kv1.3 Ion Channel

    PubMed Central

    Kovach, Christopher P.; Al Koborssy, Dolly; Huang, Zhenbo; Chelette, Brandon M.; Fadool, James M.; Fadool, Debra A.

    2016-01-01

    Gene-targeted deletion of the potassium channel Kv1.3 (Kv1.3−∕−) results in “Super-smeller” mice with a sensory phenotype that includes an increased olfactory ability linked to changes in olfactory circuitry, increased abundance of olfactory cilia, and increased expression of odorant receptors and the G-protein, Golf. Kv1.3−∕− mice also have a metabolic phenotype including lower body weight and decreased adiposity, increased total energy expenditure (TEE), increased locomotor activity, and resistance to both diet- and genetic-induced obesity. We explored two cellular aspects to elucidate the mechanism by which loss of Kv1.3 channel in the olfactory bulb (OB) may enhance glucose utilization and metabolic rate. First, using in situ hybridization we find that Kv1.3 and the insulin-dependent glucose transporter type 4 (GLUT4) are co-localized to the mitral cell layer of the OB. Disruption of Kv1.3 conduction via construction of a pore mutation (W386F Kv1.3) was sufficient to independently translocate GLUT4 to the plasma membrane in HEK 293 cells. Because olfactory sensory perception and the maintenance of action potential (AP) firing frequency by mitral cells of the OB is highly energy demanding and Kv1.3 is also expressed in mitochondria, we next explored the structure of this organelle in mitral cells. We challenged wildtype (WT) and Kv1.3−∕− male mice with a moderately high-fat diet (MHF, 31.8 % kcal fat) for 4 months and then examined OB ultrastructure using transmission electron microscopy. In WT mice, mitochondria were significantly enlarged following diet-induced obesity (DIO) and there were fewer mitochondria, likely due to mitophagy. Interestingly, mitochondria were significantly smaller in Kv1.3−∕− mice compared with that of WT mice. Similar to their metabolic resistance to DIO, the Kv1.3−∕− mice had unchanged mitochondria in terms of cross sectional area and abundance following a challenge with modified diet. We are very

  11. Tungsten anode spectral model using interpolating cubic splines: Unfiltered x-ray spectra from 20 kV to 640 kV

    SciTech Connect

    Hernandez, Andrew M.; Boone, John M.

    2014-04-15

    Purpose: Monte Carlo methods were used to generate lightly filtered high resolution x-ray spectra spanning from 20 kV to 640 kV. Methods: X-ray spectra were simulated for a conventional tungsten anode. The Monte Carlo N-Particle eXtended radiation transport code (MCNPX 2.6.0) was used to produce 35 spectra over the tube potential range from 20 kV to 640 kV, and cubic spline interpolation procedures were used to create piecewise polynomials characterizing the photon fluence per energy bin as a function of x-ray tube potential. Using these basis spectra and the cubic spline interpolation, 621 spectra were generated at 1 kV intervals from 20 to 640 kV. The tungsten anode spectral model using interpolating cubic splines (TASMICS) produces minimally filtered (0.8 mm Be) x-ray spectra with 1 keV energy resolution. The TASMICS spectra were compared mathematically with other, previously reported spectra. Results: Using pairedt-test analyses, no statistically significant difference (i.e., p > 0.05) was observed between compared spectra over energy bins above 1% of peak bremsstrahlung fluence. For all energy bins, the correlation of determination (R{sup 2}) demonstrated good correlation for all spectral comparisons. The mean overall difference (MOD) and mean absolute difference (MAD) were computed over energy bins (above 1% of peak bremsstrahlung fluence) and over all the kV permutations compared. MOD and MAD comparisons with previously reported spectra were 2.7% and 9.7%, respectively (TASMIP), 0.1% and 12.0%, respectively [R. Birch and M. Marshall, “Computation of bremsstrahlung x-ray spectra and comparison with spectra measured with a Ge(Li) detector,” Phys. Med. Biol. 24, 505–517 (1979)], 0.4% and 8.1%, respectively (Poludniowski), and 0.4% and 8.1%, respectively (AAPM TG 195). The effective energy of TASMICS spectra with 2.5 mm of added Al filtration ranged from 17 keV (at 20 kV) to 138 keV (at 640 kV); with 0.2 mm of added Cu filtration the effective energy was 9

  12. Tungsten anode spectral model using interpolating cubic splines: Unfiltered x-ray spectra from 20 kV to 640 kV

    PubMed Central

    Hernandez, Andrew M.; Boone, John M.

    2014-01-01

    Purpose: Monte Carlo methods were used to generate lightly filtered high resolution x-ray spectra spanning from 20 kV to 640 kV. Methods: X-ray spectra were simulated for a conventional tungsten anode. The Monte Carlo N-Particle eXtended radiation transport code (MCNPX 2.6.0) was used to produce 35 spectra over the tube potential range from 20 kV to 640 kV, and cubic spline interpolation procedures were used to create piecewise polynomials characterizing the photon fluence per energy bin as a function of x-ray tube potential. Using these basis spectra and the cubic spline interpolation, 621 spectra were generated at 1 kV intervals from 20 to 640 kV. The tungsten anode spectral model using interpolating cubic splines (TASMICS) produces minimally filtered (0.8 mm Be) x-ray spectra with 1 keV energy resolution. The TASMICS spectra were compared mathematically with other, previously reported spectra. Results: Using paired t-test analyses, no statistically significant difference (i.e., p > 0.05) was observed between compared spectra over energy bins above 1% of peak bremsstrahlung fluence. For all energy bins, the correlation of determination (R2) demonstrated good correlation for all spectral comparisons. The mean overall difference (MOD) and mean absolute difference (MAD) were computed over energy bins (above 1% of peak bremsstrahlung fluence) and over all the kV permutations compared. MOD and MAD comparisons with previously reported spectra were 2.7% and 9.7%, respectively (TASMIP), 0.1% and 12.0%, respectively [R. Birch and M. Marshall, “Computation of bremsstrahlung x-ray spectra and comparison with spectra measured with a Ge(Li) detector,” Phys. Med. Biol. 24, 505–517 (1979)], 0.4% and 8.1%, respectively (Poludniowski), and 0.4% and 8.1%, respectively (AAPM TG 195). The effective energy of TASMICS spectra with 2.5 mm of added Al filtration ranged from 17 keV (at 20 kV) to 138 keV (at 640 kV); with 0.2 mm of added Cu filtration the effective energy was 9 ke

  13. Kv11.1 (hERG)-induced cardiotoxicity: a molecular insight from a binding kinetics study of prototypical Kv11.1 (hERG) inhibitors

    PubMed Central

    Yu, Z; IJzerman, A P; Heitman, L H

    2015-01-01

    Background and Purpose Drug-induced arrhythmia due to blockade of the Kv11.1 channel (also known as the hERG K+ channel) is a frequent side effect. Previous studies have primarily focused on equilibrium parameters, i.e. affinity or potency, of drug candidates at the channel. The aim of this study was to determine the kinetics of the interaction with the channel for a number of known Kv11.1 blockers and to explore a possible correlation with the affinity or physicochemical properties of these compounds. Experimental Approach The affinity and kinetic parameters of 15 prototypical Kv11.1 inhibitors were evaluated in a number of [3H]-dofetilide binding assays. The lipophilicity (logKW-C8) and membrane partitioning (logKW-IAM) of these compounds were determined by means of HPLC analysis. Key Results A novel [3H]-dofetilide competition association assay was set up and validated, which allowed us to determine the binding kinetics of the Kv11.1 blockers used in this study. Interestingly, the compounds' affinities (Ki values) were correlated to their association rates rather than dissociation rates. Overall lipophilicity or membrane partitioning of the compounds were not correlated to their affinity or rate constants for the channel. Conclusions and Implications A compound's affinity for the Kv11.1 channel is determined by its rate of association with the channel, while overall lipophilicity and membrane affinity are not. In more general terms, our findings provide novel insights into the mechanism of action for a compound's activity at the Kv11.1 channel. This may help to elucidate how Kv11.1-induced cardiotoxicity is governed and how it can be circumvented in the future. PMID:25296617

  14. A low-latency, low-overhead encoder for data transmission in the ATLAS Liquid Argon Calorimeter trigger upgrade

    NASA Astrophysics Data System (ADS)

    Xiao, Le; Li, Xiaoting; Gong, Datao; Chen, Jinghong; Deng, Binwei; Fan, Qingjun; Feng, Yulang; Guo, Di; He, Huiqin; Hou, Suen; Huang, Guangming; Liu, Chonghan; Liu, Tiankuan; Sun, Xiangming; Tang, Yuxuan; Teng, Ping-Kun; Vosooghi, Bozorgmehr; Xiang, Annie C.; Ye, Jingbo; You, Yang; Zuo, Zhiheng

    2016-09-01

    In this paper, we present the design and test results of an encoder integrated circuit for the ATLAS Liquid Argon Calorimeter trigger upgrade. The encoder implements a low-latency and low-overhead line code called LOCic. The encoder operates at 320 MHz with a latency of no greater than 21 ns. The overhead of the encoder is 14.3%. The encoder is an important block of the transmitter ASIC LOCx2, which is prototyped with a commercial 0.25 μm Silicon-on-Sapphire CMOS technology and packaged in a 100-pin QFN package.

  15. KCNE1 remodels the voltage sensor of Kv7.1 to modulate channel function.

    PubMed

    Wu, Dick; Pan, Hua; Delaloye, Kelli; Cui, Jianmin

    2010-12-01

    The KCNE1 auxiliary subunit coassembles with the Kv7.1 channel and modulates its properties to generate the cardiac I(Ks) current. Recent biophysical evidence suggests that KCNE1 interacts with the voltage-sensing domain (VSD) of Kv7.1. To investigate the mechanism of how KCNE1 affects the VSD to alter the voltage dependence of channel activation, we perturbed the VSD of Kv7.1 by mutagenesis and chemical modification in the absence and presence of KCNE1. Mutagenesis of S4 in Kv7.1 indicates that basic residues in the N-terminal half (S4-N) and C-terminal half (S4-C) of S4 are important for stabilizing the resting and activated states of the channel, respectively. KCNE1 disrupts electrostatic interactions involving S4-C, specifically with the lower conserved glutamate in S2 (Glu(170) or E2). Likewise, Trp scanning of S4 shows that mutations to a cluster of residues in S4-C eliminate current in the presence of KCNE1. In addition, KCNE1 affects S4-N by enhancing MTS accessibility to the top of the VSD. Consistent with the structure of Kv channels and previous studies on the KCNE1-Kv7.1 interaction, these results suggest that KCNE1 alters the interactions of S4 residues with the surrounding protein environment, possibly by changing the protein packing around S4, thereby affecting the voltage dependence of Kv7.1.

  16. Novel treatment strategies for smooth muscle disorders: Targeting Kv7 potassium channels.

    PubMed

    Haick, Jennifer M; Byron, Kenneth L

    2016-09-01

    Smooth muscle cells provide crucial contractile functions in visceral, vascular, and lung tissues. The contractile state of smooth muscle is largely determined by their electrical excitability, which is in turn influenced by the activity of potassium channels. The activity of potassium channels sustains smooth muscle cell membrane hyperpolarization, reducing cellular excitability and thereby promoting smooth muscle relaxation. Research over the past decade has indicated an important role for Kv7 (KCNQ) voltage-gated potassium channels in the regulation of the excitability of smooth muscle cells. Expression of multiple Kv7 channel subtypes has been demonstrated in smooth muscle cells from viscera (gastrointestinal, bladder, myometrial), from the systemic and pulmonary vasculature, and from the airways of the lung, from multiple species, including humans. A number of clinically used drugs, some of which were developed to target Kv7 channels in other tissues, have been found to exert robust effects on smooth muscle Kv7 channels. Functional studies have indicated that Kv7 channel activators and inhibitors have the ability to relax and contact smooth muscle preparations, respectively, suggesting a wide range of novel applications for the pharmacological tool set. This review summarizes recent findings regarding the physiological functions of Kv7 channels in smooth muscle, and highlights potential therapeutic applications based on pharmacological targeting of smooth muscle Kv7 channels throughout the body.

  17. KCNE1 constrains the voltage sensor of Kv7.1 K+ channels.

    PubMed

    Shamgar, Liora; Haitin, Yoni; Yisharel, Ilanit; Malka, Eti; Schottelndreier, Hella; Peretz, Asher; Paas, Yoav; Attali, Bernard

    2008-04-09

    Kv7 potassium channels whose mutations cause cardiovascular and neurological disorders are members of the superfamily of voltage-gated K(+) channels, comprising a central pore enclosed by four voltage-sensing domains (VSDs) and sharing a homologous S4 sensor sequence. The Kv7.1 pore-forming subunit can interact with various KCNE auxiliary subunits to form K(+) channels with very different gating behaviors. In an attempt to characterize the nature of the promiscuous gating of Kv7.1 channels, we performed a tryptophan-scanning mutagenesis of the S4 sensor and analyzed the mutation-induced perturbations in gating free energy. Perturbing the gating energetics of Kv7.1 bias most of the mutant channels towards the closed state, while fewer mutations stabilize the open state or the inactivated state. In the absence of auxiliary subunits, mutations of specific S4 residues mimic the gating phenotypes produced by co-assembly of Kv7.1 with either KCNE1 or KCNE3. Many S4 perturbations compromise the ability of KCNE1 to properly regulate Kv7.1 channel gating. The tryptophan-induced packing perturbations and cysteine engineering studies in S4 suggest that KCNE1 lodges at the inter-VSD S4-S1 interface between two adjacent subunits, a strategic location to exert its striking action on Kv7.1 gating functions.

  18. Inhibitory effects of cholinesterase inhibitor donepezil on the Kv1.5 potassium channel

    PubMed Central

    Li, Kai; Cheng, Neng; Li, Xian-Tao

    2017-01-01

    Kv1.5 channels carry ultra-rapid delayed rectifier K+ currents in excitable cells, including neurons and cardiac myocytes. In the current study, the effects of cholinesterase inhibitor donepezil on cloned Kv1.5 channels expressed in HEK29 cells were explored using whole-cell recording technique. Exposure to donepezil resulted in a rapid and reversible block of Kv1.5 currents, with an IC50 value of 72.5 μM. The mutant R476V significantly reduced the binding affinity of donepezil to Kv1.5 channels, showing the target site in the outer mouth region. Donepezil produced a significant delay in the duration of activation and deactivation, and mutant R476V potentiated these effects without altering activation curves. In response to slowed deactivation time course, a typical crossover of Kv1.5 tail currents was clearly evident after bath application of donepezil. In addition, both this chemical and mutant R476V accelerated current decay during channel inactivation in a voltage-dependent way, but barely changed the inactivation and recovery curves. The presence of donepezil exhibited the use-dependent block of Kv1.5 currents in response to a series of depolarizing pulses. Our data indicate that donepezil can directly block Kv1.5 channels in its open and closed states. PMID:28198801

  19. Cloning and expression of the human kv4.3 potassium channel.

    PubMed

    Dilks, D; Ling, H P; Cockett, M; Sokol, P; Numann, R

    1999-04-01

    We report on the cloning and expression of hKv4.3, a fast inactivating, transient, A-type potassium channel found in both heart and brain that is 91% homologous to the rat Kv4.3 channel. Two isoforms of hKv4.3 were cloned. One is full length (hKv4.3 long), and the other has a 19 amino acid deletion (hKv4.3 short). RT-PCR shows that the brain contains both forms of the channel RNA, whereas the heart predominantly has the longer version. Both versions of the channel were expressed in Xenopus oocytes, and both contain a significant window or noninactivating current seen near potentials of -30 to -40 mV. The inactivation curve for hKv4.3 short is shifted 10 mV positive relative to hKv4.3 long. This causes the peak window current for the short version to occur near -30 mV and the peak for the longer version to be at -40 mV. There was little difference in the recovery from inactivation or in the kinetics of inactivation between the two isoforms of the channel.

  20. Molecular determinants of Kv1.5 channel block by diphenyl phosphine oxide-1.

    PubMed

    Du, Yi-mei; Zhang, Xiao-xian; Tu, Dan-na; Zhao, Ning; Liu, Yan-jie; Xiao, Hua; Sanguinetti, Michael C; Zou, Anruo; Liao, Yu-hua

    2010-06-01

    Kv1.5 channels conduct the ultra-rapid delayed rectifier current (I(Kur)) that contributes to action potential repolarization of human atrial myocytes. Block of these channels has been proposed as a treatment for atrial arrhythmias. Diphenyl phosphine oxide-1 (DPO-1) is a novel and potent inhibitor of Kv1.5 potassium channels. The present study was undertaken to characterize the mechanisms and molecular determinants of channel block by DPO-1. Experiments were carried out on wild-type and mutant Kv1.5 channels expressed in Xenopus laevis oocytes using the standard two microelectrode voltage clamp technique. DPO-1 blocked Kv1.5 current in oocytes with an IC(50) of 0.78+/-0.12 microM at +40 mV. Block was enhanced by higher rates of stimulation, consistent with preferential binding of the drug to the open state of the channel. Ala-scanning mutagenesis of the pore domain of Kv1.5 identified the residues Thr480, Leu499, Leu506, Ile508, Leu510 and Val514 as components of the putative binding site for DPO-1, partially overlapping the site previously defined for the Kv1.5 channel blockers AVE0118 and S0100176. Block of Kv1.5 by DPO-1 was significantly reduced in the presence of Kvbeta1.3.

  1. AMIGO is an auxiliary subunit of the Kv2.1 potassium channel.

    PubMed

    Peltola, Marjaana A; Kuja-Panula, Juha; Lauri, Sari E; Taira, Tomi; Rauvala, Heikki

    2011-12-01

    Kv2.1 is a potassium channel α-subunit abundantly expressed throughout the brain. It is a main component of delayed rectifier current (I(K)) in several neuronal types and a regulator of excitability during high-frequency firing. Here we identify AMIGO (amphoterin-induced gene and ORF), a neuronal adhesion protein with leucine-rich repeat and immunoglobin domains, as an integral part of the Kv2.1 channel complex. AMIGO shows extensive spatial and temporal colocalization and association with Kv2.1 in the mouse brain. The colocalization of AMIGO and Kv2.1 is retained even during stimulus-induced changes in Kv2.1 localization. AMIGO increases Kv2.1 conductance in a voltage-dependent manner in HEK cells. Accordingly, inhibition of endogenous AMIGO suppresses neuronal I(K) at negative membrane voltages. In conclusion, our data indicate AMIGO as a function-modulating auxiliary subunit for Kv2.1 and thus provide new insights into regulation of neuronal excitability.

  2. AMIGO is an auxiliary subunit of the Kv2.1 potassium channel

    PubMed Central

    Peltola, Marjaana A; Kuja-Panula, Juha; Lauri, Sari E; Taira, Tomi; Rauvala, Heikki

    2011-01-01

    Kv2.1 is a potassium channel α-subunit abundantly expressed throughout the brain. It is a main component of delayed rectifier current (IK) in several neuronal types and a regulator of excitability during high-frequency firing. Here we identify AMIGO (amphoterin-induced gene and ORF), a neuronal adhesion protein with leucine-rich repeat and immunoglobin domains, as an integral part of the Kv2.1 channel complex. AMIGO shows extensive spatial and temporal colocalization and association with Kv2.1 in the mouse brain. The colocalization of AMIGO and Kv2.1 is retained even during stimulus-induced changes in Kv2.1 localization. AMIGO increases Kv2.1 conductance in a voltage-dependent manner in HEK cells. Accordingly, inhibition of endogenous AMIGO suppresses neuronal IK at negative membrane voltages. In conclusion, our data indicate AMIGO as a function-modulating auxiliary subunit for Kv2.1 and thus provide new insights into regulation of neuronal excitability. PMID:22056818

  3. Effect of Methamphetamine on the Microglial Damage: Role of Potassium Channel Kv1.3

    PubMed Central

    Liu, Jingli; Zhao, Jingjing; Yu, Pan; Jiang, Lei; Zhou, Jing; Gao, Rong; Xiao, Hang

    2014-01-01

    Methamphetamine (Meth) abusing represents a major public health problem worldwide. Meth has long been known to induce neurotoxicity. However, the mechanism is still remained poorly understood. Growing evidences indicated that the voltage-gated potassium channels (Kv) were participated in neuronal damage and microglia function. With the whole cell patch clamp, we found that Meth significantly increased the outward K+ currents, therefore, we explored whether Kv1.3, one of the major K+ channels expressed in microglia, was involved in Meth-induced microglia damage. Our study showed that Meth significantly increased the cell viability in a dose dependent manner, while the Kv blocker, tetraethylamine (TEA), 4-Aminopyridine (4-AP) and Kv1.3 specific antagonist margatoxin (MgTx), prevented against the damage mediated by Meth. Interestingly, treatment of cells with Meth resulted in increasing expression of Kv1.3 rather than Kv1.5, at both mRNA and protein level, which is partially blocked by MgTx. Furthermore, Meth also stimulated a significant increased expression of IL-6 and TNF-α at protein level, which was significantly inhibited by MgTx. Taken together, these results demonstrated that Kv1.3 was involved in Meth-mediated microglial damage, providing the potential target for the development of therapeutic strategies for Meth abuse. PMID:24533129

  4. Localization and mobility of the delayed-rectifer K+ channel Kv2.1 in adult cardiomyocytes.

    PubMed

    O'Connell, Kristen M S; Whitesell, Jennifer D; Tamkun, Michael M

    2008-01-01

    The delayed-rectifier voltage-gated K(+) channel (Kv) 2.1 underlies the cardiac slow K(+) current in the rodent heart and is particularly interesting in that both its function and localization are regulated by many stimuli in neuronal systems. However, standard immunolocalization approaches do not detect cardiac Kv2.1; therefore, little is known regarding its localization in the heart. In the present study, we used recombinant adenovirus to determine the subcellular localization and lateral mobility of green fluorescent protein (GFP)-Kv2.1 and yellow fluorescent protein-Kv1.4 in atrial and ventricular myocytes. In atrial myocytes, Kv2.1 formed large clusters on the cell surface similar to those observed in hippocampal neurons, whereas Kv1.4 was evenly distributed over both the peripheral sarcolemma and the transverse tubules. However, fluorescence recovery after photobleach (FRAP) experiments indicate that atrial Kv2.1 was immobile, whereas Kv1.4 was mobile (tau = 252 +/- 42 s). In ventricular myocytes, Kv2.1 did not form clusters and was localized primarily in the transverse-axial tubules and sarcolemma. In contrast, Kv1.4 was found only in transverse tubules and sarcolemma. FRAP studies revealed that Kv2.1 has a higher mobility in ventricular myocytes (tau = 479 +/- 178 s), although its mobility is slower than Kv1.4 (tau(1) = 18.9 +/- 2.3 s; tau(2) = 305 +/- 55 s). We also observed the movement of small, intracellular transport vesicles containing GFP-Kv2.1 within ventricular myocytes. These data are the first evidence of Kv2.1 localization in living myocytes and indicate that Kv2.1 may have distinct physiological roles in atrial and ventricular myocytes.

  5. Distribution of Kv1-like potassium channels in the electromotor and electrosensory systems of the weakly electric fish Apteronotus leptorhynchus.

    PubMed

    Smith, G Troy; Unguez, Graciela A; Weber, Christopher M

    2006-08-01

    The electromotor and electrosensory systems of the weakly electric fish Apteronotus leptorhynchus are model systems for studying mechanisms of high-frequency motor pattern generation and sensory processing. Voltage-dependent ionic currents, including low-threshold potassium currents, influence excitability of neurons in these circuits and thereby regulate motor output and sensory filtering. Although Kv1-like potassium channels are likely to carry low-threshold potassium currents in electromotor and electrosensory neurons, the distribution of Kv1 alpha subunits in A. leptorhynchus is unknown. In this study, we used immunohistochemistry with six different antibodies raised against specific mammalian Kv1 alpha subunits (Kv1.1-Kv1.6) to characterize the distribution of Kv1-like channels in electromotor and electrosensory structures. Each Kv1 antibody labeled a distinct subset of neurons, fibers, and/or dendrites in electromotor and electrosensory nuclei. Kv1-like immunoreactivity in the electrosensory lateral line lobe (ELL) and pacemaker nucleus are particularly relevant in light of previous studies suggesting that potassium currents carried by Kv1 channels regulate neuronal excitability in these regions. Immunoreactivity of pyramidal cells in the ELL with several Kv1 antibodies is consistent with Kv1 channels carrying low-threshold outward currents that regulate spike waveform in these cells (Fernandez et al., J Neurosci 2005;25:363-371). Similarly, Kv1-like immunoreactivity in the pacemaker nucleus is consistent with a role of Kv1 channels in spontaneous high-frequency firing in pacemaker neurons. Robust Kv1-like immunoreactivity in several other structures, including the dorsal torus semicircularis, tuberous electroreceptors, and the electric organ, indicates that Kv1 channels are broadly expressed and are likely to contribute significantly to generating the electric organ discharge and processing electrosensory inputs.

  6. Friction and wear of some ceramics in an overhead finger follower system

    SciTech Connect

    Eyre, T.S.; Benson, J.

    1986-01-01

    A laboratory bench rig based upon a Ford overhead finger follower system has been designed, constructed and extensively used for metals lubrication studies. In this work ceramics have been substituted for cast iron and steel follower materials and direct comparisons have been made under conditions where the metals perform rather poorly. All these tests have been carried out with a base oil at 100/sup 0/C for a period of 20 hours. For silicon carbide and sialon a considerable reduction in friction has been obtained and this has resulted in considerably less wear of the follower surfaces. Wear of the cam nose is also considerably reduced. It has been concluded that some ceramics perform very well and in conjunction with their low density, should find wide applications as inserts in the conventionally lubricated internal combustion engine.

  7. Failure of Vapor Overheads Discharge Line for a Radioactive Waste Evaporator

    SciTech Connect

    Jenkins, C.F.

    2004-01-20

    A 2-inch schedule 40 steel core pipe in an evaporator overheads discharge line broke at several locations downstream from a section of the line where it bridges a road. Fish mouth openings that developed along the pipe seams were initiated at lack of fusion defects in the pipe welds. A vacuum created in the piping upstream of the breaks prevented full drainage of the water upon shut down of the pump. Freezing of water in the pipe (the line was not heat traced) and water hammer effects occurring with pump restart could each contribute to the extensive deformation and tearing observed at the breaks. Both the weld flaws and the over pressure contributed to the outcome. All pipe was replaced and a vacuum break was installed to eliminate the problem.

  8. A Hybrid Quorum Protocol for Improved Availability, Capacity, Load and Reduced Overhead

    NASA Astrophysics Data System (ADS)

    Pandey, Parul; Tripathi, Maheshwari

    2016-12-01

    Data replication is playing a vital role in the design of distributed information systems. This paper presents a novel and efficient distributed algorithm for managing replicated data and for better performance and availability. This paper presents an extension to existing wheel protocol for improved performance. Wheel protocol imposes a logical wheel structure on the set of copies of an object and gives smallest read quorum. In addition to small read quorum size for read intensive applications, it is necessary to have good write availability as well. This paper proposes two hybrid wheel protocols, which superimpose logarithmic and ring protocols on top of the wheel protocol. It shows that, both protocols help in improving write availability, read capacity, load and message overhead and also compare their performances with wheel and other protocols. Hybrid protocols expand usage of wheel protocol to different type of applications.

  9. Time Granularity Transformation of Time Series Data for Failure Prediction of Overhead Line

    NASA Astrophysics Data System (ADS)

    Ma, Yan; Zhu, Wenbing; Yao, Jinxia; Gu, Chao; Bai, Demeng; Wang, Kun

    2017-01-01

    In this paper, we give an approach of transforming time series data with different time granularities into the same plane, which is the basis of further association analysis. We focus on the application of overhead line tripping. First all the relative state variables with line tripping are collected into our big data platform. We collect line account, line fault, lightning, power load and meteorological data. Second we respectively pre-process the five kinds of data to guarantee the integrality of data and simplicity of analysis. We use a representation way combining the aggregated representation and trend extraction methods, which considers both short term variation and long term trend of time sequence. Last we use extensive experiments to demonstrate that the proposed time granularity transformation approach not only lets multiple variables analysed on the same plane, but also has a high prediction accuracy and low running time no matter for SVM or logistic regression algorithm.

  10. Minimizing resource overheads for fault-tolerant preparation of encoded states of the Steane code.

    PubMed

    Goto, Hayato

    2016-01-27

    The seven-qubit quantum error-correcting code originally proposed by Steane is one of the best known quantum codes. The Steane code has a desirable property that most basic operations can be performed easily in a fault-tolerant manner. A major obstacle to fault-tolerant quantum computation with the Steane code is fault-tolerant preparation of encoded states, which requires large computational resources. Here we propose efficient state preparation methods for zero and magic states encoded with the Steane code, where the zero state is one of the computational basis states and the magic state allows us to achieve universality in fault-tolerant quantum computation. The methods minimize resource overheads for the fault-tolerant state preparation, and therefore reduce necessary resources for quantum computation with the Steane code. Thus, the present results will open a new possibility for efficient fault-tolerant quantum computation.

  11. The value of preliminary overhead traction in the closed management of DDH

    PubMed Central

    Murnaghan, Claire; Synder, Marek

    2006-01-01

    We aimed to discover whether there is a difference in incidence of growth disturbances of the proximal femoral epiphysis and final results in two similar groups of children with developmental dislocation of the hip (DDH) treated with (107 hips) and without (48 hips) overhead traction. The only variable between the groups was the use of preliminary traction. All children were followed up until at least the age of 14 years. Pre-reduction traction should be used among children treated non-operatively for DDH who are older than one year of age and/or have high-dislocated hips. In cases that are diagnosed late, this treatment would reduce the risk of severe growth disturbances and increase the probability of a favourable long-term outcome. PMID:16521010

  12. Effects of height and load weight on shoulder muscle work during overhead lifting task.

    PubMed

    Blache, Y; Desmoulins, L; Allard, P; Plamondon, A; Begon, M

    2015-01-01

    Few musculoskeletal models are available to assess shoulder deeper muscle demand during overhead lifting tasks. Our objective was to implement a musculoskeletal model to assess the effect of lifting height and load on shoulder muscle work. A musculoskeletal model scaled from 15 male subjects was used to calculate shoulder muscle work during six lifting tasks. Boxes containing three different loads (6, 12 and 18 kg) were lifted by the subjects from the waist to shoulder or eye level. After optimisation of the maximal isometric force of the model's muscles, the bio-fidelity of the model was improved by 19%. The latter was able to reproduce the subjects' lifting movements. Mechanical work of the rotator cuff muscles, upper trapezius and anterior deltoid was increased with lifting load and height augmentation. In conclusion, the use of a musculoskeletal model validated by electromyography enabled to evaluate the muscle demand of deep muscles during lifting tasks.

  13. Cam pully and cylinder head arrangement for an overhead cam engine

    SciTech Connect

    Hudson, E.B.

    1991-01-08

    This patent describes improvement in an air-cooled internal combustion engine. It includes a crankcase, a crankshaft disposed within the crankcase and extending externally of the crankcase, a cylinder extending from the crankcase and having a piston mounted for reciprocation therein and connected to the crankshaft, a cylinder head connected to the cylinder and including an overhead camshaft disposed therein, the camshaft extending externally of the cylinder head, a drive pulley mounted to the crankshaft externally of the crankcases, a cam pulley mounted to the camshaft externally of the cylinder head, drive means positively engaging the drive pulley and the cam pulley for transmitting rotary motion therebetween, and blower means driven by the crankshaft for drawing air in and blowing the air over the cylinder head. The improvement comprises: the cam pulley including means for directing air axially toward the cylinder head upon rotation of the cam pulley.

  14. Evaluating Effects of H2O and overhead O3 on Global Mean Tropospheric OH Concentration

    NASA Technical Reports Server (NTRS)

    Nicely, Julie M.; Salawitch, R.J.; Canty, T.; Lang, Chang; Duncan, Bryan; Liang, Qing; Oman, Luke David; Stolarski, Richard S.; Waugh, Darryn

    2012-01-01

    The oxidizing capacity of the troposphere is controlled, to a large extent, by the abundance of hydroxyl radical (OH). The global mean concentration of OH, [OH]GLOBAL, inferred from measurements of methyl chloroform, has remained relatively constant during the past several decades, despite rising levels of CH4 that should have led to a steady decline. Here we examine other factors that may have affected [OH]GLOBAL, such as the overhead burden of stratospheric O3 and tropospheric H2O, using global OH fields from the GEOS-CHEM Chemistry-Climate Model. Our analysis suggests these factors may have contributed a positive trend to [OH]GLOBAL large enough to counter the decrease due to CH4.

  15. Characterization Results for the March 2016 H-Tank Farm 2H Evaporator Overhead Samples

    SciTech Connect

    Nicholson, J. C.

    2016-09-28

    This report contains the radioanalytical results of the 2H evaporator overhead sample received at SRNL on March 16, 2016. Specifically, concentrations of 137Cs, 90Sr, and 129I are reported and compared to the corresponding Waste Acceptance Criteria (WAC) limits of the Effluent Treatment Project (ETP) Waste Water Collection Tank (WWCT) (rev. 6). All of the radionuclide concentrations in the sample were found to be in compliance with the ETP WAC limits. Revision 1 of this document corrects the cumulative beta count initially reported for 90Sr content with the sole 90Sr count obtained after recharacterization of the sample. The initial data was found to be a cumulative beta count rather than the 90Sr count requested.

  16. A note on the charging of aerosols by overhead line corona.

    PubMed

    Jeffers, D

    2001-01-01

    Elevated concentrations of corona ions have been measured in the vicinity of high voltage overhead lines. It is shown that the integrated ion exposure of aerosols in the corona plume is of the order of (x/u)n(x) where n(x) is the ion concentration at distance x downwind from the line and u is the wind speed. Estimated ion exposures are of order 10(11) m(-3) x s, less then 1% of the 10(13) m(-3) x s needed to cause saturation charging of 20 nm aerosols. It is suggested that it is not valid to postulate that AC corona is a health hazard as a consequence of its charging aerosols in the size range 20-125 nm.

  17. Voltages induced on a power distribution line by overhead cloud lightning

    NASA Technical Reports Server (NTRS)

    Yacoub, Ziad; Rubinstein, Marcos; Uman, Martin A.; Thomson, Ewen M.; Medelius, Pedro J.

    1991-01-01

    Voltages induced by overhead cloud lightning on a 448 m open circuited power distribution line and the corresponding north-south component of the lightning magnetic field were simultaneously measured at the NASA Kennedy Space Center during the summer of 1986. The incident electric field was calculated from the measured magnetic field. The electric field was then used as an input to the computer program, EMPLIN, that calculated the voltages at the two ends of the power line. EMPLIN models the frequency domain field/power coupling theory found, for example, in Ianoz et al. The direction of the source, which is also one of the inputs to EMPLIN, was crudely determined from a three station time delay technique. The authors found reasonably good agreement between calculated and measured waveforms.

  18. Kv3.1 channels stimulate adult neural precursor cell proliferation and neuronal differentiation.

    PubMed

    Yasuda, Takahiro; Cuny, Hartmut; Adams, David J

    2013-05-15

    Adult neural stem/precursor cells (NPCs) play a pivotal role in neuronal plasticity throughout life. Among ion channels identified in adult NPCs, voltage-gated delayed rectifier K(+) (KDR) channels are dominantly expressed. However, the KDR channel subtype and its physiological role are still undefined. We used real-time quantitative RT-PCR and gene knockdown techniques to identify a major functional KDR channel subtype in adult NPCs. Dominant mRNA expression of Kv3.1, a high voltage-gated KDR channel, was quantitatively confirmed. Kv3.1 gene knockdown with specific small interfering RNAs (siRNA) for Kv3.1 significantly inhibited Kv3.1 mRNA expression by 63.9% (P < 0.001) and KDR channel currents by 52.2% (P < 0.001). This indicates that Kv3.1 is the subtype responsible for producing KDR channel outward currents. Resting membrane properties, such as resting membrane potential, of NPCs were not affected by Kv3.1 expression. Kv3.1 knockdown with 300 nm siRNA inhibited NPC growth (increase in cell numbers) by 52.9% (P < 0.01). This inhibition was attributed to decreased cell proliferation, not increased cell apoptosis. We also established a convenient in vitro imaging assay system to evaluate NPC differentiation using NPCs from doublecortin-green fluorescent protein transgenic mice. Kv3.1 knockdown also significantly reduced neuronal differentiation by 31.4% (P < 0.01). We have demonstrated that Kv3.1 is a dominant functional KDR channel subtype expressed in adult NPCs and plays key roles in NPC proliferation and neuronal lineage commitment during differentiation.

  19. BMP signaling controls PASMC KV channel expression in vitro and in vivo.

    PubMed

    Young, Katharine A; Ivester, Charles; West, James; Carr, Michelle; Rodman, David M

    2006-05-01

    Bone morphogenetic proteins (BMPs) have been implicated in the pathogenesis of familial pulmonary arterial hypertension. The type 2 receptor (BMPR2) is required for recognition of all BMPs. Transgenic mice with a smooth muscle cell-targeted mutation in this receptor (SM22-tet-BMPR2(delx4+)) developed increased pulmonary artery pressure, associated with a modest increase in arterial muscularization, after 8 wk of transgene activation (West J, Fagan K, Steudel W, Fouty B, Lane K, Harral J, Hoedt-Miller M, Tada Y, Ozimek J, Tuder R, and Rodman DM. Circ Res 94: 1109-1114, 2004). In the present study, we show that these transgenic mice developed increased right ventricular pressures after only 1 wk of transgene activation, without significant remodeling of the vasculature. We then tested the hypothesis that the increased pulmonary artery pressure due to loss of BMPR2 signaling was mediated by reduced K(V) channel expression. There was decreased expression of K(V)1.1, K(V)1.5, and K(V)4.3 mRNA isolated from whole lung. Western blot confirmed decreased K(V)1.5 protein in these lungs. Human pulmonary artery smooth muscle cells (PASMC) treated with recombinant BMP2 had increased K(V)1.5 protein and macroscopic K(V) current density, which was blocked by anti-K(V)1.5 antibody. In vivo, nifedipine, a selective L-type Ca(2+) channel blocker, reduced RV systolic pressure in these dominant-negative BMPR2 mice to levels seen in control animals. This suggests that activation of L-type Ca(2+) channels caused by reduced K(V)1.5 mediates increased pulmonary artery pressure in these animals. These studies suggest that BMP regulates K(V) channel expression and that loss of this signaling pathway in PASMC through a mutation in BMPR2 is sufficient to cause pulmonary artery vasoconstriction.

  20. Membrane cholesterol modulates Kv1.5 potassium channel distribution and function in rat cardiomyocytes.

    PubMed

    Abi-Char, Joëlle; Maguy, Ange; Coulombe, Alain; Balse, Elise; Ratajczak, Philippe; Samuel, Jane-Lise; Nattel, Stanley; Hatem, Stéphane N

    2007-08-01

    Membrane lipid composition is a major determinant of cell excitability. In this study, we assessed the role of membrane cholesterol composition in the distribution and function of Kv1.5-based channels in rat cardiac membranes. In isolated rat atrial myocytes, the application of methyl-beta-cyclodextrin (MCD), an agent that depletes membrane cholesterol, caused a delayed increase in the Kv1.5-based sustained component, I(kur), which reached steady state in approximately 7 min. This effect was prevented by preloading the MCD with cholesterol. MCD-increased current was inhibited by low 4-aminopyridine concentration. Neonatal rat cardiomyocytes transfected with Green Fluorescent Protein (GFP)-tagged Kv1.5 channels showed a large ultrarapid delayed-rectifier current (I(Kur)), which was also stimulated by MCD. In atrial cryosections, Kv1.5 channels were mainly located at the intercalated disc, whereas caveolin-3 predominated at the cell periphery. A small portion of Kv1.5 floated in the low-density fractions of step sucrose-gradient preparations. In live neonatal cardiomyocytes, GFP-tagged Kv1.5 channels were predominantly organized in clusters at the basal plasma membrane. MCD caused reorganization of Kv1.5 subunits into larger clusters that redistributed throughout the plasma membrane. The MCD effect on clusters was sizable 7 min after its application. We conclude that Kv1.5 subunits are concentrated in cholesterol-enriched membrane microdomains distinct from caveolae, and that redistribution of Kv1.5 subunits by depletion of membrane cholesterol increases their current-carrying capacity.

  1. Single particle image reconstruction of the human recombinant Kv2.1 channel.

    PubMed

    Adair, Brian; Nunn, Rashmi; Lewis, Shannon; Dukes, Iain; Philipson, Louis; Yeager, Mark

    2008-03-15

    Kv2.1 channels are widely expressed in neuronal and endocrine cells and generate slowly activating K+ currents, which contribute to repolarization in these cells. Kv2.1 is expressed at high levels in the mammalian brain and is a major component of the delayed rectifier current in the hippocampus. In addition, Kv2.1 channels have been implicated in the regulation of membrane repolarization, cytoplasmic calcium levels, and insulin secretion in pancreatic beta-cells. They are therefore an important drug target for the treatment of Type II diabetes mellitus. We used electron microscopy and single particle image analysis to derive a three-dimensional density map of recombinant human Kv2.1. The tetrameric channel is egg-shaped with a diameter of approximately 80 A and a long axis of approximately 120 A. Comparison to known crystal structures of homologous domains allowed us to infer the location of the cytoplasmic and transmembrane assemblies. There is a very good fit of the Kv1.2 crystal structure to the assigned transmembrane assembly of Kv2.1. In other low-resolution maps of K+ channels, the cytoplasmic N-terminal and transmembrane domains form separate rings of density. In contrast, Kv2.1 displays contiguous density that connects the rings, such that there are no large windows between the channel interior and the cytoplasmic space. The crystal structure of KcsA is thought to be in a closed conformation, and the good fit of the KcsA crystal structure to the Kv2.1 map suggests that our preparations of Kv2.1 may also represent a closed conformation. Substantial cytoplasmic density is closely associated with the T1 tetramerization domain and is ascribed to the approximately 184 kDa C-terminal regulatory domains within each tetramer.

  2. Single Particle Image Reconstruction of the Human Recombinant Kv2.1 Channel

    PubMed Central

    Adair, Brian; Nunn, Rashmi; Lewis, Shannon; Dukes, Iain; Philipson, Louis; Yeager, Mark

    2008-01-01

    Kv2.1 channels are widely expressed in neuronal and endocrine cells and generate slowly activating K+ currents, which contribute to repolarization in these cells. Kv2.1 is expressed at high levels in the mammalian brain and is a major component of the delayed rectifier current in the hippocampus. In addition, Kv2.1 channels have been implicated in the regulation of membrane repolarization, cytoplasmic calcium levels, and insulin secretion in pancreatic β-cells. They are therefore an important drug target for the treatment of Type II diabetes mellitus. We used electron microscopy and single particle image analysis to derive a three-dimensional density map of recombinant human Kv2.1. The tetrameric channel is egg-shaped with a diameter of ∼80 Å and a long axis of ∼120 Å. Comparison to known crystal structures of homologous domains allowed us to infer the location of the cytoplasmic and transmembrane assemblies. There is a very good fit of the Kv1.2 crystal structure to the assigned transmembrane assembly of Kv2.1. In other low-resolution maps of K+ channels, the cytoplasmic N-terminal and transmembrane domains form separate rings of density. In contrast, Kv2.1 displays contiguous density that connects the rings, such that there are no large windows between the channel interior and the cytoplasmic space. The crystal structure of KcsA is thought to be in a closed conformation, and the good fit of the KcsA crystal structure to the Kv2.1 map suggests that our preparations of Kv2.1 may also represent a closed conformation. Substantial cytoplasmic density is closely associated with the T1 tetramerization domain and is ascribed to the ∼184 kDa C-terminal regulatory domains within each tetramer. PMID:18212012

  3. Membrane cholesterol modulates Kv1.5 potassium channel distribution and function in rat cardiomyocytes

    PubMed Central

    Abi-Char, Joëlle; Maguy, Ange; Coulombe, Alain; Balse, Elise; Ratajczak, Philippe; Samuel, Jane-Lise; Nattel, Stanley; Hatem, Stéphane N

    2007-01-01

    Membrane lipid composition is a major determinant of cell excitability. In this study, we assessed the role of membrane cholesterol composition in the distribution and function of Kv1.5-based channels in rat cardiac membranes. In isolated rat atrial myocytes, the application of methyl-β-cyclodextrin (MCD), an agent that depletes membrane cholesterol, caused a delayed increase in the Kv1.5-based sustained component, Ikur, which reached steady state in ∼7 min. This effect was prevented by preloading the MCD with cholesterol. MCD-increased current was inhibited by low 4-aminopyridine concentration. Neonatal rat cardiomyocytes transfected with Green Fluorescent Protein (GFP)-tagged Kv1.5 channels showed a large ultrarapid delayed-rectifier current (IKur), which was also stimulated by MCD. In atrial cryosections, Kv1.5 channels were mainly located at the intercalated disc, whereas caveolin-3 predominated at the cell periphery. A small portion of Kv1.5 floated in the low-density fractions of step sucrose-gradient preparations. In live neonatal cardiomyocytes, GFP-tagged Kv1.5 channels were predominantly organized in clusters at the basal plasma membrane. MCD caused reorganization of Kv1.5 subunits into larger clusters that redistributed throughout the plasma membrane. The MCD effect on clusters was sizable 7 min after its application. We conclude that Kv1.5 subunits are concentrated in cholesterol-enriched membrane microdomains distinct from caveolae, and that redistribution of Kv1.5 subunits by depletion of membrane cholesterol increases their current-carrying capacity. PMID:17525113

  4. Kv3 channels contribute to the delayed rectifier current in small cultured mouse dorsal root ganglion neurons.

    PubMed

    Bocksteins, Elke; Van de Vijver, Gerda; Van Bogaert, Pierre-Paul; Snyders, Dirk J

    2012-08-15

    Delayed rectifier voltage-gated K(+) (K(V)) channels are important determinants of neuronal excitability. However, the large number of K(V) subunits poses a major challenge to establish the molecular composition of the native neuronal K(+) currents. A large part (∼60%) of the delayed rectifier current (I(K)) in small mouse dorsal root ganglion (DRG) neurons has been shown to be carried by both homotetrameric K(V)2.1 and heterotetrameric channels of K(V)2 subunits with silent K(V) subunits (K(V)S), while a contribution of K(V)1 channels has also been demonstrated. Because K(V)3 subunits also generate delayed rectifier currents, we investigated the contribution of K(V)3 subunits to I(K) in small mouse DRG neurons. After stromatoxin (ScTx) pretreatment to block the K(V)2-containing component, application of 1 mM TEA caused significant additional block, indicating that the ScTx-insensitive part of I(K) could include K(V)1, K(V)3, and/or M-current channels (KCNQ2/3). Combining ScTx and dendrotoxin confirmed a relevant contribution of K(V)2 and K(V)2/K(V)S, and K(V)1 subunits to I(K) in small mouse DRG neurons. After application of these toxins, a significant TEA-sensitive current (∼19% of total I(K)) remained with biophysical properties that corresponded to those of K(V)3 currents obtained in expression systems. Using RT-PCR, we detected K(V)3.1-3 mRNA in DRG neurons. Furthermore, Western blot and immunocytochemistry using K(V)3.1-specific antibodies confirmed the presence of K(V)3.1 in cultured DRG neurons. These biophysical, pharmacological, and molecular results demonstrate a relevant contribution (∼19%) of K(V)3-containing channels to I(K) in small mouse DRG neurons, supporting a substantial role for K(V)3 subunits in these neurons.

  5. Raloxifene inhibits cloned Kv4.3 channels in an estrogen receptor-independent manner.

    PubMed

    Chae, Yun Ju; Kim, Dae Hun; Lee, Hong Joon; Sung, Ki-Wug; Kwon, Oh-Joo; Hahn, Sang June

    2015-08-01

    Raloxifene is widely used for the treatment and prevention of postmenopausal osteoporosis. We examined the effects of raloxifene on the Kv4.3 currents expressed in Chinese hamster ovary (CHO) cells using the whole-cell patch-clamp technique and on the long-term modulation of Kv4.3 messenger RNA (mRNA) by real-time PCR analysis. Raloxifene decreased the Kv4.3 currents with an IC50 of 2.0 μM and accelerated the inactivation and activation kinetics in a concentration-dependent manner. The inhibitory effects of raloxifene on Kv4.3 were time-dependent: the association and dissociation rate constants for raloxifene were 9.5 μM(-1) s(-1) and 23.0 s(-1), respectively. The inhibition by raloxifene was voltage-dependent (δ = 0.13). Raloxifene shifted the steady-state inactivation curves in a hyperpolarizing direction and accelerated the closed-state inactivation of Kv4.3. Raloxifene slowed the time course of recovery from inactivation, thus producing a use-dependent inhibition of Kv4.3. β-Estradiol and tamoxifen had little effect on Kv4.3. A preincubation of ICI 182,780, an estrogen receptor antagonist, for 1 h had no effect on the inhibitory effect of raloxifene on Kv4.3. The metabolites of raloxifene, raloxifene-4'-glucuronide and raloxifene-6'-glucuronide, had little or no effect on Kv4.3. Coexpression of KChIP2 subunits did not alter the drug potency and steady-state inactivation of Kv4.3 channels. Long-term exposure to raloxifene (24 h) significantly decreased the expression level of Kv4.3 mRNA. This effect was not abolished by the coincubation with ICI 182,780. Raloxifene inhibited Kv4.3 channels by interacting with their open state during depolarization and with the closed state at subthreshold potentials. This effect was not mediated via an estrogen receptor.

  6. Design, construction, and operational results of an 800-A, 10-kV hot deck amplifier

    SciTech Connect

    Reass, W.A.

    1984-06-01

    This paper describes the electrical design, implementation, and operational results of a high fidelity (feedback regulated) 800 A, 10-kV hard tube, hot deck amplifier. The amplifier can produce any linear waveform to 800-A for 30 ms and beyond (depending on main energy storage). The present use is to drive the vertical field (VF) control windings on ZT-40M, a toroidal reversed field pinch plasma physics experiment. Although our application requires only 10 kV (8 MW) of switching, anode voltage may be as high as 40 kV (32 MW).

  7. A selective blocker of Kv1.2 and Kv1.3 potassium channels from the venom of the scorpion Centruroides suffusus suffusus.

    PubMed

    Corzo, Gerardo; Papp, Ferenc; Varga, Zoltan; Barraza, Omar; Espino-Solis, Pavel G; Rodríguez de la Vega, Ricardo C; Gaspar, Rezso; Panyi, Gyorgy; Possani, Lourival D

    2008-10-30

    A novel potassium channel blocker peptide was purified from the venom of the scorpion Centruroides suffusus suffusus by high-performance liquid chromatography and its amino acid sequence was completed by Edman degradation and mass spectrometry analysis. It contains 38 amino acid residues with a molecular weight of 4000.3Da, tightly folded by three disulfide bridges. This peptide, named Css20, was shown to block preferentially the currents of the voltage-dependent K+-channels Kv1.2 and Kv1.3. It did not affect several other ion channels tested at 10 nM concentration. Concentration-response curves of Css20 yielded an IC50 of 1.3 and 7.2 nM for Kv1.2- and Kv1.3-channels, respectively. Interestingly, despite the similar affinities for the two channels the association and dissociation rates of the toxin were much slower for Kv1.2, implying that different interactions may be involved in binding to the two channel types; an implication further supported by in silico docking analyses. Based on the primary structure of Css20, the systematic nomenclature proposed for this toxin is alpha-KTx 2.13.

  8. How does KCNE1 regulate the Kv7.1 potassium channel? Model-structure, mutations, and dynamics of the Kv7.1-KCNE1 complex.

    PubMed

    Gofman, Yana; Shats, Simona; Attali, Bernard; Haliloglu, Turkan; Ben-Tal, Nir

    2012-08-08

    The voltage-gated potassium channel Kv7.1 and its auxiliary subunit KCNE1 are expressed in the heart and give rise to the major repolarization current. The interaction of Kv7.1 with the single transmembrane helix of KCNE1 considerably slows channel activation and deactivation, raises single-channel conductance, and prevents slow voltage-dependent inactivation. We built a Kv7.1-KCNE1 model-structure. The model-structure agrees with previous disulfide mapping studies and enables us to derive molecular interpretations of electrophysiological recordings that we obtained for two KCNE1 mutations. An elastic network analysis of Kv7.1 fluctuations in the presence and absence of KCNE1 suggests a mechanistic perspective on the known effects of KCNE1 on Kv7.1 function: slow deactivation is attributed to the low mobility of the voltage-sensor domains upon KCNE1 binding, abolishment of voltage-dependent inactivation could result from decreased fluctuations in the external vestibule, and amalgamation of the fluctuations in the pore region is associated with enhanced ion conductivity.

  9. Kv3.3 immunoreactivity in the vestibular nuclear complex of the rat with focus on the medial vestibular nucleus: targeting of Kv3.3 neurones by terminals positive for vesicular glutamate transporter 1.

    PubMed

    Brooke, Ruth Elizabeth; Corns, Laura; Edwards, Ian James; Deuchars, Jim

    2010-07-23

    Kv3 voltage-gated K(+) channels are important in shaping neuronal excitability and are abundant in the CNS, with each Kv3 gene exhibiting a unique expression pattern. Mice lacking the gene encoding for the Kv3.3 subunit exhibit motor deficits. Furthermore, mutations in this gene have been linked to the human disease spinocerebellar ataxia 13, associated with cerebellar and extra-cerebellar symptoms such as imbalance and nystagmus. Kv subunit localisation is important in defining their functional roles and thus, we investigated the distribution of Kv3.3-immunoreactivity in the vestibular nuclear complex of rats with particular focus on the medial vestibular nucleus (MVN). Kv3.3-immunoreactivity was widespread in the vestibular nuclei and was detected in somata, dendrites and synaptic terminals. Kv3.3-immunoreactivity was observed in distinct neuronal populations and dual labelling with the neuronal marker NeuN revealed 28.5+/-1.9% of NeuN labelled MVN neurones were Kv3.3-positive. Kv3.3-immunoreactivity co-localised presynaptically with the synaptic vesicle marker SV2, parvalbumin, the vesicular glutamate transporter VGluT2 and the glycine transporter GlyT2. VGluT1 terminals were scarce within the MVN (2.5+/-1.1 per 50 microm(2)) and co-localisation was not observed. However, 85.4+/-9.4% of VGluT1 terminals targeted and enclosed Kv3.3-immunoreactive somata. Presynaptic Kv3.3 co-localisation with the GABAergic marker GAD67 was also not observed. Cytoplasmic GlyT2 labelling was observed in a subset of Kv3.3-positive neurones. Electron microscopy confirmed a pre- and post-synaptic distribution of the Kv3.3 protein. This study provides evidence supporting a role for Kv3.3 subunits in vestibular processing by regulating neuronal excitability pre- and post-synaptically.

  10. Kv4.2 and accessory dipeptidyl peptidase-like protein 10 (DPP10) subunit preferentially form a 4:2 (Kv4.2:DPP10) channel complex.

    PubMed

    Kitazawa, Masahiro; Kubo, Yoshihiro; Nakajo, Koichi

    2015-09-11

    Kv4 is a member of the voltage-gated K(+) channel family and forms a complex with various accessory subunits. Dipeptidyl aminopeptidase-like protein (DPP) is one of the auxiliary subunits for the Kv4 channel. Although DPP has been well characterized and is known to increase the current amplitude and accelerate the inactivation and recovery from inactivation of Kv4 current, it remains to be determined how many DPPs bind to one Kv4 channel. To examine whether the expression level of DPP changes the biophysical properties of Kv4, we expressed Kv4.2 and DPP10 in different ratios in Xenopus oocytes and analyzed the currents under two-electrode voltage clamp. The current amplitude and the speed of recovery from inactivation of Kv4.2 changed depending on the co-expression level of DPP10. This raised the possibility that the stoichiometry of the Kv4.2-DPP10 complex is variable and affects the biophysical properties of Kv4.2. We next determined the stoichiometry of DPP10 alone by subunit counting using single-molecule imaging. Approximately 70% of the DPP10 formed dimers in the plasma membrane, and the rest existed as monomers in the absence of Kv4.2. We next determined the stoichiometry of the Kv4.2-DPP10 complex; Kv4.2-mCherry and mEGFP-DPP10 were co-expressed in different ratios and the stoichiometries of Kv4.2-DPP10 complexes were evaluated by the subunit counting method. The stoichiometry of the Kv4.2-DPP10 complex was variable depending on the relative expression level of each subunit, with a preference for 4:2 stoichiometry. This preference may come from the bulky dimeric structure of the extracellular domain of DPP10.

  11. Upregulation of functional Kv11.1 isoform expression by inhibition of intronic polyadenylation with antisense morpholino oligonucleotides.

    PubMed

    Gong, Qiuming; Stump, Matthew R; Zhou, Zhengfeng

    2014-11-01

    The KCNH2 gene encodes the Kv11.1 potassium channel that conducts the rapidly activating delayed rectifier current in the heart. KCNH2 pre-mRNA undergoes alternative processing; intron 9 splicing leads to the formation of a functional, full-length Kv11.1a isoform, while polyadenylation within intron 9 generates a non-functional, C-terminally truncated Kv11.1a-USO isoform. The relative expression of Kv11.1 isoforms plays an important role in the regulation of Kv11.1 channel function and the pathogenesis of long QT syndrome. In this study, we identified cis-acting elements that are required for KCNH2 intron 9 poly(A) signal activity. Mutation of these elements decreased Kv11.1a-USO expression and increased the expression of Kv11.1a mRNA, protein and channel current. More importantly, blocking these elements by antisense morpholino oligonucleotides shifted the alternative processing of KCNH2 intron 9 from the polyadenylation to the splicing pathway, leading to the predominant production of Kv11.1a and a significant increase in Kv11.1 current. Our findings indicate that the expression of the Kv11.1a isoform can be upregulated by an antisense approach. Antisense inhibition of KCNH2 intronic polyadenylation represents a novel approach to increase Kv11.1 channel function.

  12. Stimulation of glucose uptake in murine soleus muscle and adipocytes by 5-(4-phenoxybutoxy)psoralen (PAP-1) may be mediated by Kv1.5 rather than Kv1.3

    PubMed Central

    Ngala, Robert A.; Zaibi, Mohamed S.; Langlands, Kenneth; Stocker, Claire J.; Cawthorne, Michael A.

    2014-01-01

    Kv1 channels are shaker-related potassium channels that influence insulin sensitivity. Kv1.3−/− mice are protected from diet-induced insulin resistance and some studies suggest that Kv1.3 inhibitors provide similar protection. However, it is unclear whether blockade of Kv1.3 in adipocytes or skeletal muscle increases glucose uptake. There is no evidence that the related channel Kv1.5 has any influence on insulin sensitivity and its expression in adipose tissue has not been reported. PAP-1 is a selective inhibitor of Kv1.3, with 23-fold, 32-fold and 125-fold lower potencies as an inhibitor of Kv1.5, Kv1.1 and Kv1.2 respectively. Soleus muscles from wild-type and genetically obese ob/ob mice were incubated with 2-deoxy[1-14C]-glucose for 45 min and formation of 2-deoxy[1-14C]-glucose-6-phosphate was measured. White adipocytes were incubated with D-[U-14C]-glucose for 1 h. TNFα and Il-6 secretion from white adipose tissue pieces were measured by enzyme-linked-immunoassay. In the absence of insulin, a high concentration (3 µM) of PAP-1 stimulated 2-deoxy[1-14C]-glucose uptake in soleus muscle of wild-type and obese mice by 30% and 40% respectively, and in adipocytes by 20% and 50% respectively. PAP-1 also stimulated glucose uptake by adipocytes at the lower concentration of 1 µM, but at 300 nM, which is still 150-fold higher than its EC50 value for inhibition of the Kv1.3 channel, it had no effect. In the presence of insulin, PAP-1 (3 µM) had a significant effect only in adipocytes from obese mice. PAP-1 (3 µM) reduced the secretion of TNFα by adipose tissue but had no effect on the secretion of IL-6. Expression of Kv1.1, Kv1.2, Kv1.3 and Kv1.5 was determined by RT-PCR. Kv1.3 and Kv1.5 mRNA were detected in liver, gastrocnemius muscle, soleus muscle and white adipose tissue from wild-type and ob/ob mice, except that Kv1.3 could not be detected in gastrocnemius muscle, nor Kv1.5 in liver, of wild-type mice. Expression of both genes was generally higher in

  13. CEBAF 200 kV Inverted Electron Gun

    SciTech Connect

    Grames, J M; Clark, J; Hansknecht, J; Poelker, M; Stutzman, M L; Suleiman, R; Surles-Law, K.E.L.; BastaniNejad, M; McCarter, J J

    2011-03-01

    Two DC high volt­age GaAs pho­to­guns have been built at Jef­fer­son Lab based on a com­pact in­vert­ed in­su­la­tor de­sign. One pho­to­gun pro­vides the po­lar­ized elec­tron beam at CEBAF and op­er­ates at 130 kV bias volt­age. The other gun is used for high av­er­age cur­rent life­time stud­ies at a ded­i­cat­ed test fa­cil­i­ty and has been op­er­at­ed at bias volt­age up to 225 kV. The ad­van­tages of high­er DC volt­age for CEBAF in­clude re­duced space-charge emit­tance growth and the po­ten­tial for pro­longed pho­to­cath­ode life­time. How­ev­er, a con­se­quence of op­er­at­ing at high­er volt­ages is the in­creased like­li­hood of field emis­sion or break­down, both of which are un­ac­cept­able. High­lights of the R&D stud­ies lead­ing to­ward a pro­duc­tion 200keV GaAs pho­to­gun for CEBAF will be pre­sent­ed.

  14. NIOSH alert: Request for assistance in preventing electrocutions of crane operators and crew members working near overhead power lines

    SciTech Connect

    1995-05-01

    In this alert, NIOSH warned that crane operators and crew members may be electrocuted when working near overhead power lines. Five cases were described which resulted in six electrocutions. Case 1 involved a 29 year old who pushed the crane cable on a 1 yard cement bucket into a 7,200 volt power line. Case 2 involved a 33 year old well driller who was electrocuted when a metal pipe lifted by a truck mounted crane contacted a 12,000 volt overhead power line. The third case involved a 24 year old forman for a telecommunications company who was electrocuted when he grabbed the door handle of a truck mounted crane whose boom was in contact with a 7,200 volt overhead power line. Case 4 involved a 37 year old construction laborer electrocuted while pulling a wire rope attached to a crane cable toward a load. The fifth case involved a 20 year old male truck driver and his 70 year old male employer who were electrocuted when the boom of a truck mounted crane contacted a 7,200 volt conductor of an overhead power line.

  15. Business Activity Monitoring: Real-Time Group Goals and Feedback Using an Overhead Scoreboard in a Distribution Center

    ERIC Educational Resources Information Center

    Goomas, David T.; Smith, Stuart M.; Ludwig, Timothy D.

    2011-01-01

    Companies operating large industrial settings often find delivering timely and accurate feedback to employees to be one of the toughest challenges they face in implementing performance management programs. In this report, an overhead scoreboard at a retailer's distribution center informed teams of order selectors as to how many tasks were…

  16. Development and modification of a single overhead camshaft 4-valve 4-stroke 135 cc formula varsity race car engine

    NASA Astrophysics Data System (ADS)

    Abdullah, M. A.; Tamaldin, N.; Rusnandi, H.; Manoharan, T.; Samsir, M. A.

    2013-12-01

    The engine that was chosen to be developed and modified is Yamaha LC 135 Single Overhead Camshaft (SOHC) 4-valve 4-stroke 135cc liquid-cooled engine. The engine selection is based on the specification, rule and regulation in UTeM Formula Varsity 2012 (FV 2012). The engine performance is determined by engine operating characteristics. The engine air flow affects the filtration, intake and exhaust systems. The heat from the engine rejected to the surrounding through the active cooling system which has radiator and fan. The selection of the engine is based on weighted decision matrix which consists of reliability, operating and maintenance cost, fuel consumption and weight. The score of the matrix is formulated based on relative weighted factor among the selections. It been compared between Yamaha LC 135 Single Overhead Camshaft (SOHC) 4-valve 4-stroke 135cc liquid-cooled engine, Honda Wave 125 X Air Cooled, 4 Cycle Engine Overhead Camshaft (OHC) and Suzuki Shogun RR 4 stroke air cooled Single Overhead Camshaft (SOHC). The modification is applied to the engine through the simulation and tuning of Capacitor Discharge Ignition (CDI).

  17. 76 FR 44246 - Special Conditions: Boeing Model 747-8 Series Airplanes; Overhead Flight Attendant Rest Compartment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-25

    ... minute quantities of flammable fluids (e.g., finger nail polish and aerosol hairspray) that would pose no... requirements were developed. This requirement originated from a concern that a fire in an unoccupied overhead... agent originating in the OFAR compartment from entering any other compartment occupied by crewmembers...

  18. 75 FR 33320 - Notice of Issuance of Final Determination Concerning a Lift Unit for an Overhead Patient Lift...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-11

    ... notice that it had issued a final determination concerning the country of origin of a lift unit for an... Code of Federal Regulations (CFR) concerning the country of origin of a lift unit for an overhead... determination concerning the country of origin of the lift unit which may be offered to the U.S....

  19. Functional torque ratios and torque curve analysis of shoulder rotations in overhead athletes with and without impingement symptoms.

    PubMed

    Zanca, Gisele G; Oliveira, Ana B; Saccol, Michele F; Ejnisman, Benno; Mattiello-Rosa, Stela M

    2011-12-01

    In this study, we evaluated the peak torque, functional torque ratios, and torque curve profile of the shoulder rotators in overhead athletes with impingement symptoms so as to examine possible alterations in response to sports training and shoulder pain. Twenty-one overhead athletes with impingement symptoms were compared with 25 overhead athletes and 21 non-athletes, none of whom were symptomatic for impingement. The participants performed five maximal isokinetic concentric and eccentric contractions of medial and lateral shoulder rotations at 1.57 rad · s(-1) and 3.14 rad · s(-1). Isokinetic peak torque was used to calculate the eccentric lateral rotation-to-concentric medial rotation and the eccentric medial rotation-to-concentric lateral rotation ratios. An analysis of the torque curve profiles was also carried out. The eccentric lateral rotation-to-concentric medial rotation torque ratio of asymptomatic athletes was lower than that of non-athletes at both test velocities. The concentric medial rotation isokinetic peak torque of the asymptomatic athletes, at 3.14 rad · s(-1), was greater than that of the non-athletes, and the peak appeared to occur earlier in the movement for athletes than non-athletes. These findings suggest that there may be adaptations to shoulder function in response to throwing practice. The eccentric medial rotation-to-concentric lateral rotation torque ratio was altered neither by the practice of university-level overhead sports nor impingement symptoms.

  20. Overexpression of tau downregulated the mRNA levels of Kv channels and improved proliferation in N2A cells.

    PubMed

    Li, Xiantao; Hu, Ximu; Li, Xiaoqing; Hao, Xuran

    2015-01-01

    Microtubule binding protein tau has a crucial function in promoting the assembly and stabilization of microtubule. Besides tuning the action potentials, voltage-gated K+ channels (Kv) are important for cell proliferation and appear to play a role in the development of cancer. However, little is known about the possible interaction of tau with Kv channels in various tissues. In the present study, tau plasmids were transiently transfected into mouse neuroblastoma N2A cells to explore the possible linkages between tau and Kv channels. This treatment led to a downregulation of mRNA levels of several Kv channels, including Kv2.1, Kv3.1, Kv4.1, Kv9.2, and KCNH4, but no significant alteration was observed for Kv5.1 and KCNQ4. Furthermore, the macroscopic currents through Kv channels were reduced by 36.5% at +60 mV in tau-transfected N2A cells. The proliferation rates of N2A cells were also improved by the induction of tau expression and the incubation of TEA (tetraethylammonium) for 48 h by 120.9% and 149.3%, respectively. Following the cotransfection with tau in HEK293 cells, the mRNA levels and corresponding currents of Kv2.1 were significantly declined compared with single Kv2.1 transfection. Our data indicated that overexpression of tau declined the mRNA levels of Kv channels and related currents. The effects of tau overexpression on Kv channels provided an alternative explanation for low sensitivity to anti-cancer chemicals in some specific cancer tissues.

  1. Overexpression of Tau Downregulated the mRNA Levels of Kv Channels and Improved Proliferation in N2A Cells

    PubMed Central

    Li, Xiantao; Hu, Ximu; Li, Xiaoqing; Hao, Xuran

    2015-01-01

    Microtubule binding protein tau has a crucial function in promoting the assembly and stabilization of microtubule. Besides tuning the action potentials, voltage-gated K+ channels (Kv) are important for cell proliferation and appear to play a role in the development of cancer. However, little is known about the possible interaction of tau with Kv channels in various tissues. In the present study, tau plasmids were transiently transfected into mouse neuroblastoma N2A cells to explore the possible linkages between tau and Kv channels. This treatment led to a downregulation of mRNA levels of several Kv channels, including Kv2.1, Kv3.1, Kv4.1, Kv9.2, and KCNH4, but no significant alteration was observed for Kv5.1 and KCNQ4. Furthermore, the macroscopic currents through Kv channels were reduced by 36.5% at +60 mV in tau-tranfected N2A cells. The proliferation rates of N2A cells were also improved by the induction of tau expression and the incubation of TEA (tetraethylammonium) for 48 h by 120.9% and 149.3%, respectively. Following the cotransfection with tau in HEK293 cells, the mRNA levels and corresponding currents of Kv2.1 were significantly declined compared with single Kv2.1 transfection. Our data indicated that overexpression of tau declined the mRNA levels of Kv channels and related currents. The effects of tau overexpression on Kv channels provided an alternative explanation for low sensitivity to anti-cancer chemicals in some specific cancer tissues. PMID:25590133

  2. Suppression of slow delayed rectifier current by a truncated isoform of KvLQT1 cloned from normal human heart.

    PubMed

    Jiang, M; Tseng-Crank, J; Tseng, G N

    1997-09-26

    It has been suggested that the cardiac slow delayed rectifier channel is formed by the association of two subunits: IsK (also called minK) and KvLQT1. N-terminal splice variants of the human KvLQT1 gene have been identified, but the functional roles of different KvLQT1 isoforms are not clear. Using the nested 5'-rapid amplification of cDNA ends technique, we obtained a truncated isoform of KvLQT1 (termed tKvLQT1) that lacks the N-terminal cytoplasmic domain and the initial one-third of the first transmembrane domain. The function of tKvLQT1 was tested by oocyte expression, alone or together with the full-length KvLQT1 or a human IsK clone (hIsK). tKvLQT1 alone did not generate functional channels. However, it suppressed the KvLQT1 current when coexpressed with the full-length isoform. It also suppressed the slow delayed rectifier current induced by hIsK, probably by competing with the KvLQT1 subunit endogenous to Xenopus oocytes in coassembly with the hIsK subunit. On the other hand, tKvLQT1 did not suppress the expression of Kv1.4, Kv4.3, or hERG. Using the reverse transcription-polymerase chain reaction technique, we further show that the truncated and full-length isoforms are coexpressed in different regions of human heart. Therefore, tKvLQT1 may modulate the function of IKs in human cardiac myocytes.

  3. Resilient RTN fast spiking in Kv3.1 null mice suggests redundancy in the action potential repolarization mechanism.

    PubMed

    Porcello, Darrell M; Ho, Chi Shun; Joho, Rolf H; Huguenard, John R

    2002-03-01

    Fast spiking (FS), GABAergic neurons of the reticular thalamic nucleus (RTN) are capable of firing high-frequency trains of brief action potentials, with little adaptation. Studies in recombinant systems have shown that high-voltage-activated K(+) channels containing the Kv3.1 and/or Kv3.2 subunits display biophysical properties that may contribute to the FS phenotype. Given that RTN expresses high levels of Kv3.1, with little or no Kv3.2, we tested whether this subunit was required for the fast action potential repolarization mechanism essential to the FS phenotype. Single- and multiple-action potentials were recorded using whole-cell current clamp in RTN neurons from brain slices of wild-type and Kv3.1-deficient mice. At 23 degrees C, action potentials recorded from homozygous Kv3.1 deficient mice (Kv3.1(-/-)) compared with their wild-type (Kv3.1(+/+)) counterparts had reduced amplitudes (-6%) and fast after-hyperpolarizations (-16%). At 34 degrees C, action potentials in Kv3.1(-/-) mice had increased duration (21%) due to a reduced rate of repolarization (-30%) when compared with wild-type controls. Action potential trains in Kv3.1(-/-) were associated with a significantly greater spike decrement and broadening and a diminished firing frequency versus injected current relationship (F/I) at 34 degrees C. There was no change in either spike count or maximum instantaneous frequency during low-threshold Ca(2+) bursts in Kv3.1(-/-) RTN neurons at either temperature tested. Our findings show that Kv3.1 is not solely responsible for fast spikes or high-frequency firing in RTN neurons. This suggests genetic redundancy in the system, possibly in the form of other Kv3 members, which may suffice to maintain the FS phenotype in RTN neurons in the absence of Kv3.1.

  4. Role of Kv 4.3 in vibration-induced muscle pain in the rat

    PubMed Central

    Conner, Lindsay; Alvarez, Pedro; Bogen, Oliver; Levine, Jon D.

    2015-01-01

    We hypothesized that changes in the expression of Kv4.3 contribute to the mechanical hyperalgesia induced by vibration injury, a rodent model for hand-arm vibration syndrome in humans. Here we show that the exposure of the gastrocnemius muscle to vibration injury induces muscle hyperalgesia that is accompanied by a significant down-regulation of Kv4.3 in affected sensory nerve fibers in dorsal root ganglia (DRG). We additionally demonstrate that the intrathecal administration of antisense oligonucleotides for Kv4.3 mRNA itself induces muscle hyperalgesia in the rat. Our results suggest that attenuation in the expression of Kv4.3 may contribute to neuropathic pain in people affected by hand-arm vibration syndrome. PMID:26721612

  5. PKC and AMPK regulation of Kv1.5 potassium channels

    PubMed Central

    Andersen, Martin Nybo; Skibsbye, Lasse; Tang, Chuyi; Petersen, Frederic; MacAulay, Nanna; Rasmussen, Hanne Borger; Jespersen, Thomas

    2015-01-01

    The voltage-gated Kv1.5 potassium channel, conducting the ultra-rapid rectifier K+ current (IKur), is regulated through several pathways. Here we investigate if Kv1.5 surface expression is controlled by the 2 kinases PKC and AMPK, using Xenopus oocytes, MDCK cells and atrial derived HL-1 cells. By confocal microscopy combined with electrophysiology we demonstrate that PKC activation reduces Kv1.5 current, through a decrease in membrane expressed channels. AMPK activation was found to decrease the membrane expression in MDCK cells, but not in HL-1 cells and was furthermore shown to be dependent on co-expression of Nedd4–2 in Xenopus oocytes. These results indicate that Kv1.5 channels are regulated by both kinases, although through different molecular mechanisms in different cell systems. PMID:26043299

  6. Axon initial segment Kv1 channels control axonal action potential waveform and synaptic efficacy.

    PubMed

    Kole, Maarten H P; Letzkus, Johannes J; Stuart, Greg J

    2007-08-16

    Action potentials are binary signals that transmit information via their rate and temporal pattern. In this context, the axon is thought of as a transmission line, devoid of a role in neuronal computation. Here, we show a highly localized role of axonal Kv1 potassium channels in shaping the action potential waveform in the axon initial segment (AIS) of layer 5 pyramidal neurons independent of the soma. Cell-attached recordings revealed a 10-fold increase in Kv1 channel density over the first 50 microm of the AIS. Inactivation of AIS and proximal axonal Kv1 channels, as occurs during slow subthreshold somatodendritic depolarizations, led to a distance-dependent broadening of axonal action potentials, as well as an increase in synaptic strength at proximal axonal terminals. Thus, Kv1 channels are strategically positioned to integrate slow subthreshold signals, providing control of the presynaptic action potential waveform and synaptic coupling in local cortical circuits.

  7. Toxins Targeting the Kv1.3 Channel: Potential Immunomodulators for Autoimmune Diseases.

    PubMed

    Zhao, Yipeng; Huang, Jie; Yuan, Xiaolu; Peng, Biwen; Liu, Wanhong; Han, Song; He, Xiaohua

    2015-05-19

    Autoimmune diseases are usually accompanied by tissue injury caused by autoantigen-specific T-cells. KV1.3 channels participate in modulating calcium signaling to induce T-cell proliferation, immune activation and cytokine production. Effector memory T (TEM)-cells, which play major roles in many autoimmune diseases, are controlled by blocking KV1.3 channels on the membrane. Toxins derived from animal venoms have been found to selectively target a variety of ion channels, including KV1.3. By blocking the KV1.3 channel, these toxins are able to suppress the activation and proliferation of TEM cells and may improve TEM cell-mediated autoimmune diseases, such as multiple sclerosis and type I diabetes mellitus.

  8. Development of 600 kV triple resonance pulse transformer.

    PubMed

    Li, Mingjia; Zhang, Faqiang; Liang, Chuan; Xu, Zhou

    2015-06-01

    In this paper, a triple-resonance pulse transformer based on an air-core transformer is introduced. The voltage across the high-voltage winding of the air-core transformer is significantly less than the output voltage; instead, the full output voltage appears across the tuning inductor. The maximum ratio of peak load voltage to peak transformer voltage is 2.77 in theory. By analyzing pulse transformer's lossless circuit, the analytical expression for the output voltage and the characteristic equation of the triple-resonance circuit are presented. Design method for the triple-resonance pulse transformer (iterated simulation method) is presented, and a triple-resonance pulse transformer is developed based on the existing air-core transformer. The experimental results indicate that the maximum ratio of peak voltage across the load to peak voltage across the high-voltage winding of the air-core transformer is approximately 2.0 and the peak output voltage of the triple-resonance pulse transformer is approximately 600 kV.

  9. Putative binding sites for arachidonic acid on the human cardiac Kv1.5 channel

    PubMed Central

    Bai, Jia‐Yu; Ding, Wei‐Guang; Kojima, Akiko; Seto, Tomoyoshi

    2015-01-01

    Background and Purpose In human heart, the Kv1.5 channel contributes to repolarization of atrial action potentials. This study examined the electrophysiological and molecular mechanisms underlying arachidonic acid (AA)‐induced inhibition of the human Kv1.5 (hKv1.5) channel. Experimental Approach Site‐directed mutagenesis was conducted to mutate amino acids that reside within the pore domain of the hKv1.5 channel. Whole‐cell patch‐clamp method was used to record membrane currents through wild type and mutant hKv1.5 channels heterologously expressed in CHO cells. Computer docking simulation was conducted to predict the putative binding site(s) of AA in an open‐state model of the Kv1.5 channel. Key Results The hKv1.5 current was minimally affected at the onset of depolarization but was progressively reduced during depolarization by the presence of AA, suggesting that AA acts as an open‐channel blocker. AA itself affected the channel at extracellular sites independently of its metabolites and signalling pathways. The blocking effect of AA was attenuated at pH 8.0 but not at pH 6.4. The blocking action of AA developed rather rapidly by co‐expression of Kvβ1.3. The AA‐induced block was significantly attenuated in H463C, T480A, R487V, I502A, I508A, V512A and V516A, but not in T462C, A501V and L510A mutants of the hKv1.5 channel. Docking simulation predicted that H463, T480, R487, I508, V512 and V516 are potentially accessible for interaction with AA. Conclusions and Implications AA itself interacts with multiple amino acids located in the pore domain of the hKv1.5 channel. These findings may provide useful information for future development of selective blockers of hKv1.5 channels. PMID:26292661

  10. Measurements of electric and magnetic fields, in heavy vehicles parking space, in the vicinity of a power station with 150kv to 20kv transformers

    NASA Astrophysics Data System (ADS)

    Gkanatsios, Stavros; Grigorescu, S.; Pliatsios, A.; Gkanatsiou, M.; Panagiotou, E.; Boukouvala, E.; Gavros, K.; Mitropoulos, D.

    2016-11-01

    The present paper investigates the electric and magnetic fields of extremely low frequencies in substations which step down voltage in Kozani, which is a city of about 65.000 inhabitants. In the substation, apart from the presence of voltage distribution transformers there are also power cables of 150 kV generated in pillars as well as power cables of 20 kV and 380V for the power supply of the city. Pillars with high, medium and low voltage power cables cross the parking space of heavy vehicles.

  11. Kv4.2 knockout mice display learning and memory deficits in the Lashley maze

    PubMed Central

    Smith, Gregory D.; Gao, Nan; Lugo, Joaquin N.

    2017-01-01

    Background: Potassium channels have been shown to be involved in neural plasticity and learning. Kv4.2 is a subunit of the A-type potassium channel. Kv4.2 channels modulate excitability in the dendrites of pyramidal neurons in the cortex and hippocampus. Deletion of Kv4.2 results in spatial learning and conditioned fear deficits; however, previous studies have only examined deletion of Kv4.2 in aversive learning tests. Methods: For the current study, we used the Lashley maze as an appetitive learning test. We examined Kv4.2 wildtype (WT) and knockout (KO) mice in the Lashley maze over 4 days during adulthood. The first day consisted of habituating the mice to the maze. The mice then received five trials per day for the next 3 days. The number of errors and the time to the goal box was recorded for each trial. The goal box contained a weigh boat with an appetitive reward (gelatin with sugar). There was an intertrial interval of 15 minutes. Results: We found that Kv4.2 KO mice committed more errors across the trials compared to the WT mice p<0.001. There was no difference in the latency to find the goal box over the period. Discussion: Our finding that deletion of Kv4.2 resulted in more errors in the Lashley maze across 15 trials contribute to a growing body of evidence that Kv4.2 channels are significantly involved in learning and memory. PMID:28163893

  12. A dipeptidyl aminopeptidase-like protein remodels gating charge dynamics in Kv4.2 channels.

    PubMed

    Dougherty, Kevin; Covarrubias, Manuel

    2006-12-01

    Dipeptidyl aminopeptidase-like proteins (DPLPs) interact with Kv4 channels and thereby induce a profound remodeling of activation and inactivation gating. DPLPs are constitutive components of the neuronal Kv4 channel complex, and recent observations have suggested the critical functional role of the single transmembrane segment of these proteins (Zagha, E., A. Ozaita, S.Y. Chang, M.S. Nadal, U. Lin, M.J. Saganich, T. McCormack, K.O. Akinsanya, S.Y. Qi, and B. Rudy. 2005. J. Biol. Chem. 280:18853-18861). However, the underlying mechanism of action is unknown. We hypothesized that a unique interaction between the Kv4.2 channel and a DPLP found in brain (DPPX-S) may remodel the channel's voltage-sensing domain. To test this hypothesis, we implemented a robust experimental system to measure Kv4.2 gating currents and study gating charge dynamics in the absence and presence of DPPX-S. The results demonstrated that coexpression of Kv4.2 and DPPX-S causes a -26 mV parallel shift in the gating charge-voltage (Q-V) relationship. This shift is associated with faster outward movements of the gating charge over a broad range of relevant membrane potentials and accelerated gating charge return upon repolarization. In sharp contrast, DPPX-S had no effect on gating charge movements of the Shaker B Kv channel. We propose that DPPX-S destabilizes resting and intermediate states in the voltage-dependent activation pathway, which promotes the outward gating charge movement. The remodeling of gating charge dynamics may involve specific protein-protein interactions of the DPPX-S's transmembrane segment with the voltage-sensing and pore domains of the Kv4.2 channel. This mechanism may determine the characteristic fast operation of neuronal Kv4 channels in the subthreshold range of membrane potentials.

  13. Voltage-dependent metabolic regulation of Kv2.1 channels in pancreatic beta-cells.

    PubMed

    Yoshida, Masashi; Nakata, Masanori; Yamato, Shiho; Dezaki, Katsuya; Sugawara, Hitoshi; Ishikawa, San-e; Kawakami, Masanobu; Yada, Toshihiko; Kakei, Masafumi

    2010-05-28

    Voltage-gated potassium channels (Kv channels) play a crucial role in formation of action potentials in response to glucose stimulation in pancreatic beta-ells. We previously reported that the Kv channel is regulated by glucose metabolism, particularly by MgATP. We examined whether the regulation of Kv channels is voltage-dependent and mechanistically related with phosphorylation of the channels. In rat pancreatic beta-cells, suppression of glucose metabolism with low glucose concentrations of 2.8mM or less or by metabolic inhibitors decreased the Kv2.1-channel activity at positive membrane potentials, while increased it at potentials negative to -10 mV, suggesting that modulation of Kv channels by glucose metabolism is voltage-dependent. Similarly, in HEK293 cells expressing the recombinant Kv2.1 channels, 0mM but not 10mM MgATP modulated the channel activity in a manner similar to that in beta-cells. Both steady-state activation and inactivation kinetics of the channel were shifted toward the negative potential in association with the voltage-dependent modulation of the channels by cytosolic dialysis of alkaline phosphatase in beta-cells. The modulation of Kv-channel current-voltage relations were also observed during and after glucose-stimulated electrical excitation. These results suggest that the cellular metabolism including MgATP production and/or channel phosphorylation/dephosphorylation underlie the physiological modulation of Kv2.1 channels during glucose-induced insulin secretion.

  14. Thalamic Kv7 channels: pharmacological properties and activity control during noxious signal processing

    PubMed Central

    Cerina, Manuela; Szkudlarek, Hanna J; Coulon, Philippe; Meuth, Patrick; Kanyshkova, Tatyana; Nguyen, Xuan Vinh; Göbel, Kerstin; Seidenbecher, Thomas; Meuth, Sven G; Pape, Hans-Christian; Budde, Thomas

    2015-01-01

    Background and Purpose The existence of functional Kv7 channels in thalamocortical (TC) relay neurons and the effects of the K+-current termed M-current (IM) on thalamic signal processing have long been debated. Immunocytochemical evidence suggests their presence in this brain region. Therefore, we aimed to verify their existence, pharmacological properties and function in regulating activity in neurons of the ventrobasal thalamus (VB). Experimental Approach Characterization of Kv7 channels was performed by combining in vitro, in vivo and in silico techniques with a pharmacological approach. Retigabine (30 μM) and XE991 (20 μM), a specific Kv7 channel enhancer and blocker, respectively, were applied in acute brain slices during electrophysiological recordings. The effects of intrathalamic injection of retigabine (3 mM, 300 nL) and/or XE991 (2 mM, 300 nL) were investigated in freely moving animals during hot-plate tests by recording behaviour and neuronal activity. Key Results Kv7.2 and Kv7.3 subunits were found to be abundantly expressed in TC neurons of mouse VB. A slow K+-current with properties of IM was activated by retigabine and inhibited by XE991. Kv7 channel activation evoked membrane hyperpolarization, a reduction in tonic action potential firing, and increased burst firing in vitro and in computational models. Single-unit recordings and pharmacological intervention demonstrated a specific burst-firing increase upon IM activation in vivo. A Kv7 channel-mediated increase in pain threshold was associated with fewer VB units responding to noxious stimuli, and increased burst firing in responsive neurons. Conclusions and Implications Kv7 channel enhancement alters somatosensory activity and may reflect an anti-nociceptive mechanism during acute pain processing. PMID:25684311

  15. Protein kinase C modulates inactivation of Kv3.3 channels.

    PubMed

    Desai, Rooma; Kronengold, Jack; Mei, Jianfeng; Forman, Stuart A; Kaczmarek, Leonard K

    2008-08-08

    Modulation of some Kv3 family potassium channels by protein kinase C (PKC) regulates their amplitude and kinetics and adjusts firing patterns of auditory neurons in response to stimulation. Nevertheless, little is known about the modulation of Kv3.3, a channel that is widely expressed throughout the nervous system and is the dominant Kv3 family member in auditory brainstem. We have cloned the cDNA for the Kv3.3 channel from mouse brain and have expressed it in a mammalian cell line and in Xenopus oocytes to characterize its biophysical properties and modulation by PKC. Kv3.3 currents activate at positive voltages and undergo inactivation with time constants of 150-250 ms. Activators of PKC increased current amplitude and removed inactivation of Kv3.3 currents, and a specific PKC pseudosubstrate inhibitor peptide prevented the effects of the activators. Elimination of the first 78 amino acids of the N terminus of Kv3.3 produced noninactivating currents suggesting that PKC modulates N-type inactivation, potentially by phosphorylation of sites in this region. To identify potential phosphorylation sites, we investigated the response of channels in which serines in this N-terminal domain were subjected to mutagenesis. Our results suggest that serines at positions 3 and 9 are potential PKC phosphorylation sites. Computer simulations of model neurons suggest that phosphorylation of Kv3.3 by PKC may allow neurons to maintain action potential height during stimulation at high frequencies, and may therefore contribute to stimulus-induced changes in the intrinsic excitability of neurons such as those of the auditory brainstem.

  16. Kv7 channels regulate pairwise spiking covariability in health and disease.

    PubMed

    Ocker, Gabriel Koch; Doiron, Brent

    2014-07-15

    Low-threshold M currents are mediated by the Kv7 family of potassium channels. Kv7 channels are important regulators of spiking activity, having a direct influence on the firing rate, spike time variability, and filter properties of neurons. How Kv7 channels affect the joint spiking activity of populations of neurons is an important and open area of study. Using a combination of computational simulations and analytic calculations, we show that the activation of Kv7 conductances reduces the covariability between spike trains of pairs of neurons driven by common inputs. This reduction is beyond that explained by the lowering of firing rates and involves an active cancellation of common fluctuations in the membrane potentials of the cell pair. Our theory shows that the excess covariance reduction is due to a Kv7-induced shift from low-pass to band-pass filtering of the single neuron spike train response. Dysfunction of Kv7 conductances is related to a number of neurological diseases characterized by both elevated firing rates and increased network-wide correlations. We show how changes in the activation or strength of Kv7 conductances give rise to excess correlations that cannot be compensated for by synaptic scaling or homeostatic modulation of passive membrane properties. In contrast, modulation of Kv7 activation parameters consistent with pharmacological treatments for certain hyperactivity disorders can restore normal firing rates and spiking correlations. Our results provide key insights into how regulation of a ubiquitous potassium channel class can control the coordination of population spiking activity.

  17. Kv3.1 uses a timely resurgent K(+) current to secure action potential repolarization.

    PubMed

    Labro, Alain J; Priest, Michael F; Lacroix, Jérôme J; Snyders, Dirk J; Bezanilla, Francisco

    2015-12-17

    High-frequency action potential (AP) transmission is essential for rapid information processing in the central nervous system. Voltage-dependent Kv3 channels play an important role in this process thanks to their high activation threshold and fast closure kinetics, which reduce the neuron's refractory period. However, premature Kv3 channel closure leads to incomplete membrane repolarization, preventing sustainable AP propagation. Here, we demonstrate that Kv3.1b channels solve this problem by producing resurgent K(+) currents during repolarization, thus ensuring enough repolarizing power to terminate each AP. Unlike previously described resurgent Na(+) and K(+) currents, Kv3.1b's resurgent current does not originate from recovery of channel block or inactivation but results from a unique combination of steep voltage-dependent gating kinetics and ultra-fast voltage-sensor relaxation. These distinct properties are readily transferrable onto an orthologue Kv channel by transplanting the voltage-sensor's S3-S4 loop, providing molecular insights into the mechanism by which Kv3 channels contribute to high-frequency AP transmission.

  18. Physiological modulators of Kv3.1 channels adjust firing patterns of auditory brain stem neurons.

    PubMed

    Brown, Maile R; El-Hassar, Lynda; Zhang, Yalan; Alvaro, Giuseppe; Large, Charles H; Kaczmarek, Leonard K

    2016-07-01

    Many rapidly firing neurons, including those in the medial nucleus of the trapezoid body (MNTB) in the auditory brain stem, express "high threshold" voltage-gated Kv3.1 potassium channels that activate only at positive potentials and are required for stimuli to generate rapid trains of actions potentials. We now describe the actions of two imidazolidinedione derivatives, AUT1 and AUT2, which modulate Kv3.1 channels. Using Chinese hamster ovary cells stably expressing rat Kv3.1 channels, we found that lower concentrations of these compounds shift the voltage of activation of Kv3.1 currents toward negative potentials, increasing currents evoked by depolarization from typical neuronal resting potentials. Single-channel recordings also showed that AUT1 shifted the open probability of Kv3.1 to more negative potentials. Higher concentrations of AUT2 also shifted inactivation to negative potentials. The effects of lower and higher concentrations could be mimicked in numerical simulations by increasing rates of activation and inactivation respectively, with no change in intrinsic voltage dependence. In brain slice recordings of mouse MNTB neurons, both AUT1 and AUT2 modulated firing rate at high rates of stimulation, a result predicted by numerical simulations. Our results suggest that pharmaceutical modulation of Kv3.1 currents represents a novel avenue for manipulation of neuronal excitability and has the potential for therapeutic benefit in the treatment of hearing disorders.

  19. Inhibition of Kv1.3 Channels in Human Jurkat T Cells by Xanthohumol and Isoxanthohumol.

    PubMed

    Gąsiorowska, Justyna; Teisseyre, Andrzej; Uryga, Anna; Michalak, Krystyna

    2015-08-01

    Using whole-cell patch-clamp technique, we investigated influence of selected compounds from groups of prenylated chalcones and flavonoids: xanthohumol and isoxanthohumol on the activity of Kv1.3 channels in human leukemic Jurkat T cells. Obtained results provide evidence that both examined compounds were inhibitors of Kv1.3 channels in these cells. The inhibitory effects occurred in a concentration-dependent manner. The estimated value of the half-blocking concentration (EC50) was about 3 μM for xanthohumol and about 7.8 μM for isoxanthohumol. The inhibition of Kv1.3 channels by examined compounds was not complete. Upon an application of the compounds at the maximal concentrations equal to 30 μM, the activity of Kv1.3 channels was inhibited to about 0.13 of the control value. The inhibitory effect was reversible. The application of xanthohumol and isoxanthohumol did not change the currents' activation and inactivation rate. These results may confirm our earlier hypothesis that the presence of a prenyl group in a molecule is a factor that facilitates the inhibition of Kv1.3 channels by compounds from the groups of flavonoids and chalcones. The inhibition of Kv1.3 channels might be involved in antiproliferative and proapoptotic effects of the compounds observed in cancer cell lines expressing these channels.

  20. Effect of psoralen on the cloned Kv3.1 currents.

    PubMed

    Sung, Min Ji; Hahn, Sang June; Choi, Bok Hee

    2009-03-01

    The psoralen, a furocoumarin derivative, on the cloned neuronal rat Kv3.1 channels stably expressed in Chinese hamster ovary cells was investigated using the whole-cell patch-clamp technique. Psoralen reduced Kv3.1 whole-cell currents in a reversible concentration-dependent manner, with an IC50 value and a Hill coefficient of 2.3 +/- 0.03 microM and 0.9 +/- 0.08, respectively. Psoralen accelerated the decay rate of inactivation of Kv3.1 currents without modifying the kinetics of current activation. The psoralen-induced inhibition of Kv3.1 channels was voltage-dependent, with a steep increase over the voltage range of channel opening. However, the inhibition exhibited voltage independence over the voltage range in which channels are fully activated. Psoralen slowed the deactivation time course, resulting in a tail crossover phenomenon when the tail currents, recorded in the presence and absence of psoralen, were superimposed. Inhibition of Kv3.1 by psoralen was use-dependent at a frequency of 1 Hz. The present results suggest that psoralen acts on Kv3.1 currents as an open-channel blocker.

  1. Quality Assurance Plan for site electrical replacements at substation line item subproject: 69 KV Substation

    SciTech Connect

    Ohler, C.K.

    1991-05-21

    The 69 KV Substation Project is based on the recognized need to provide a continuous, reliable source of power and to improve the firm capacity of the electrical service to all production facilities at Mound. The project consists of the following major element: 69 KV Substation: (1) Install a 69 KV Substation and associated equipment with two parallel 18 MVA transformers. (2) Install duct bank as required and provide 15 KV feeder cable from new substation to existing Substation 95 for connection to Mound`s existing primary distribution system. (3) Install duct bank for underground routing of the 15 KV feeder cable from Manhole 5C to the existing power house cable pit. (4) Reconfigure existing Dayton Power and Light Co. 15 KV switchgear in P Building. The purpose of this Quality Assurance Plan (QA Plan) is to assure that the objectives of the United States Department of Energy (D.O.E.) and EG&G Mound Applied Technologies, Miamisburg, Ohio (Mound) are met for this non-weapons project relative to health and safety, protection of the environment, reliability and continuity of operations, and documentation of quality efforts. This QA Plan identifies the activities and responsibilities which are necessary in the design, procurement, fabrication, installation, and start up of this project in order to meet these objectives.

  2. Block of Kv1.7 potassium currents increases glucose-stimulated insulin secretion.

    PubMed

    Finol-Urdaneta, Rocio K; Remedi, Maria S; Raasch, Walter; Becker, Stefan; Clark, Robert B; Strüver, Nina; Pavlov, Evgeny; Nichols, Colin G; French, Robert J; Terlau, Heinrich

    2012-05-01

    Glucose-stimulated insulin secretion (GSIS) relies on repetitive, electrical spiking activity of the beta cell membrane. Cyclic activation of voltage-gated potassium channels (K(v) ) generates an outward, 'delayed rectifier' potassium current, which drives the repolarizing phase of each spike and modulates insulin release. Although several K(v) channels are expressed in pancreatic islets, their individual contributions to GSIS remain incompletely understood. We take advantage of a naturally occurring cone-snail peptide toxin, Conkunitzin-S1 (Conk-S1), which selectively blocks K(v) 1.7 channels to provide an intrinsically limited, finely graded control of total beta cell delayed rectifier current and hence of GSIS. Conk-S1 increases GSIS in isolated rat islets, likely by reducing K(v) 1.7-mediated delayed rectifier currents in beta cells, which yields increases in action potential firing and cytoplasmic free calcium. In rats, Conk-S1 increases glucose-dependent insulin secretion without decreasing basal glucose. Thus, we conclude that K(v) 1.7 contributes to the membrane-repolarizing current of beta cells during GSIS and that block of this specific component of beta cell K(v) current offers a potential strategy for enhancing GSIS with minimal risk of hypoglycaemia during metabolic disorders such as Type 2 diabetes.

  3. Induction of stable ER–plasma-membrane junctions by Kv2.1 potassium channels

    PubMed Central

    Fox, Philip D.; Haberkorn, Christopher J.; Akin, Elizabeth J.; Seel, Peter J.; Krapf, Diego; Tamkun, Michael M.

    2015-01-01

    ABSTRACT Junctions between cortical endoplasmic reticulum (cER) and the plasma membrane are a subtle but ubiquitous feature in mammalian cells; however, very little is known about the functions and molecular interactions that are associated with neuronal ER–plasma-membrane junctions. Here, we report that Kv2.1 (also known as KCNB1), the primary delayed-rectifier K+ channel in the mammalian brain, induces the formation of ER–plasma-membrane junctions. Kv2.1 localizes to dense, cell-surface clusters that contain non-conducting channels, indicating that they have a function that is unrelated to membrane-potential regulation. Accordingly, Kv2.1 clusters function as membrane-trafficking hubs, providing platforms for delivery and retrieval of multiple membrane proteins. Using both total internal reflection fluorescence and electron microscopy we demonstrate that the clustered Kv2.1 plays a direct structural role in the induction of stable ER–plasma-membrane junctions in both transfected HEK 293 cells and cultured hippocampal neurons. Glutamate exposure results in a loss of Kv2.1 clusters in neurons and subsequent retraction of the cER from the plasma membrane. We propose Kv2.1-induced ER–plasma-membrane junctions represent a new macromolecular plasma-membrane complex that is sensitive to excitotoxic insult and functions as a scaffolding site for both membrane trafficking and Ca2+ signaling. PMID:25908859

  4. Kv3.1 uses a timely resurgent K+ current to secure action potential repolarization

    PubMed Central

    Labro, Alain J.; Priest, Michael F.; Lacroix, Jérôme J.; Snyders, Dirk J.; Bezanilla, Francisco

    2015-01-01

    High-frequency action potential (AP) transmission is essential for rapid information processing in the central nervous system. Voltage-dependent Kv3 channels play an important role in this process thanks to their high activation threshold and fast closure kinetics, which reduce the neuron's refractory period. However, premature Kv3 channel closure leads to incomplete membrane repolarization, preventing sustainable AP propagation. Here, we demonstrate that Kv3.1b channels solve this problem by producing resurgent K+ currents during repolarization, thus ensuring enough repolarizing power to terminate each AP. Unlike previously described resurgent Na+ and K+ currents, Kv3.1b's resurgent current does not originate from recovery of channel block or inactivation but results from a unique combination of steep voltage-dependent gating kinetics and ultra-fast voltage-sensor relaxation. These distinct properties are readily transferrable onto an orthologue Kv channel by transplanting the voltage-sensor's S3–S4 loop, providing molecular insights into the mechanism by which Kv3 channels contribute to high-frequency AP transmission. PMID:26673941

  5. Developmental expression of potassium-channel subunit Kv3.2 within subpopulations of mouse hippocampal inhibitory interneurons.

    PubMed

    Tansey, Emily Phillips; Chow, Alan; Rudy, Bernardo; McBain, Chris J

    2002-01-01

    The developmental expression of the voltage-gated potassium channel subunit, Kv3.2, and its localization within specific mouse hippocampal inhibitory interneuron populations were determined using immunoblotting and immunohistochemical techniques. Using immunoblotting techniques, the Kv3.2 protein was weakly detected at postnatal age day 7 (P7), and full expression was attained at P21 in tissue extracts from homogenized hippocampal preparations. A similar developmental profile was observed using immunohistochemical techniques in hippocampal tissue sections. Kv3.2 protein expression was clustered on the somata and proximal dendrites of presumed inhibitory interneurons. Using double immunofluorescence, Kv3.2 subunit expression was detected on subpopulations of GABAergic inhibitory interneurons. Kv3.2 was detected in approximately 100% of parvalbumin-positive interneurons, 86% of interneurons expressing nitric oxide synthase, and approximately 50% of somatostatin-immunoreactive cells. Kv3.2 expression was absent from both calbindin- and calretinin-containing interneurons. Using immunoprecipitation, we further demonstrate that Kv3.2 and its related subunit Kv3.1b are coexpressed within the same protein complexes in the hippocampus. These data demonstrate that potassium channel subunit Kv3.2 expression is developmentally regulated in a specific set of interneurons. The vast majority of these interneuron subpopulations possess a "fast-spiking" phenotype, consistent with a role for currents through Kv3.2 containing channels in determining action potential kinetics in these cells.

  6. Kv8.1, a new neuronal potassium channel subunit with specific inhibitory properties towards Shab and Shaw channels.

    PubMed Central

    Hugnot, J P; Salinas, M; Lesage, F; Guillemare, E; de Weille, J; Heurteaux, C; Mattéi, M G; Lazdunski, M

    1996-01-01

    Outward rectifier K+ channels have a characteristic structure with six transmembrane segments and one pore region. A new member of this family of transmembrane proteins has been cloned and called Kv8.1. Kv8.1 is essentially present in the brain where it is located mainly in layers II, IV and VI of the cerebral cortex, in hippocampus, in CA1-CA4 pyramidal cell layer as well in granule cells of the dentate gyrus, in the granule cell layer and in the Purkinje cell layer of the cerebellum. The Kv8.1 gene is in the 8q22.3-8q24.1 region of the human genome. Although Kv8.1 has the hallmarks of functional subunits of outward rectifier K+ channels, injection of its cRNA in Xenopus oocytes does not produce K+ currents. However Kv8.1 abolishes the functional expression of members of the Kv2 and Kv3 subfamilies, suggesting that the functional role of Kv8.1 might be to inhibit the function of a particular class of outward rectifier K+ channel types. Immunoprecipitation studies have demonstrated that inhibition occurs by formation of heteropolymeric channels, and results obtained with Kv8.1 chimeras have indicated that association of Kv8.1 with other types of subunits is via its N-terminal domain. Images PMID:8670833

  7. Sustained upregulation in embryonic spinal neurons of a Kv3.1 potassium channel gene encoding a delayed rectifier current.

    PubMed

    Gurantz, D; Lautermilch, N J; Watt, S D; Spitzer, N C

    2000-02-15

    Differentiation of electrical excitability entails changes in the currents that generate action potentials in spinal neurons of Xenopus embryos, resulting in reduced calcium entry during impulses generated at later stages of development. A dramatic increase in delayed rectifier current (I(Kv)) during the first day of development plays the major role in this process. Identification of potassium channel genes responsible for the increase in I(Kv) is critical to understanding the molecular mechanisms involved. Several members of the Shaw Kv3 gene subfamily encode delayed rectifier currents, indicating that they could contribute to the upregulation of I(Kv) that reduces the duration of action potentials. We isolated a Xenopus (x) Kv3.1 gene whose expression is restricted to the central nervous system, which is upregulated throughout the period during which I(Kv) develops in vivo. The fraction of neurons in which transcripts of this gene are detected by single-cell RT-PCR increases to 40% with time in culture, paralleling the development of I(Kv) in neurons in vitro. Expression of xKv3.1 mRNA generates a delayed rectifier potassium current in oocytes, suggesting that xKv3. 1 contributes to the maturation of I(Kv) and shortening of the action potential.

  8. Modulation of Kv3 subfamily potassium currents by the sea anemone toxin BDS: significance for CNS and biophysical studies.

    PubMed

    Yeung, Shuk Yin M; Thompson, Dawn; Wang, Zhuren; Fedida, David; Robertson, Brian

    2005-09-21

    Kv3 potassium channels, with their ultra-rapid gating and high activation threshold, are essential for high-frequency firing in many CNS neurons. Significantly, the Kv3.4 subunit has been implicated in the major CNS disorders Parkinson's and Alzheimer's diseases, and it is claimed that selectively targeting this subunit will have therapeutic utility. Previous work suggested that BDS toxins ("blood depressing substance," from the sea anemone Anemonia sulcata) were specific blockers for rapidly inactivating Kv3.4 channels, and consequently these toxins are increasingly used as diagnostic agents for Kv3.4 subunits in central neurons. However, precisely how selective are these toxins for this important CNS protein? We show that BDS is not selective for Kv3.4 but markedly inhibits current through Kv3.1 and Kv3.2 channels. Inhibition comes about not by "pore block" but by striking modification of Kv3 gating kinetics and voltage dependence. Activation and inactivation kinetics are slowed by BDS-I and BDS-II, and V(1/2) for activation is shifted to more positive voltages. Alanine substitution mutagenesis around the S3b and S4 segments of Kv3.2 reveals that BDS acts via voltage-sensing domains, and, consistent with this, ON gating currents from nonconducting Kv3.2 are markedly inhibited. The altered kinetics and gating properties, combined with lack of subunit selectivity with Kv3 subunits, seriously affects the usefulness of BDS toxins in CNS studies. Furthermore, our results do not easily fit with the voltage sensor "paddle" structure proposed recently for Kv channels. Our data will be informative for experiments designed to dissect out the roles of Kv3 subunits in CNS function and dysfunction.

  9. Kv3.1-containing K(+) channels are reduced in untreated schizophrenia and normalized with antipsychotic drugs.

    PubMed

    Yanagi, M; Joho, R H; Southcott, S A; Shukla, A A; Ghose, S; Tamminga, C A

    2014-05-01

    Neuronal firing is a fundamental element of cerebral function; and, voltage-gated potassium (K(+)) channels regulate that firing through the repolarization of action potentials. Kv3-type channels (Kv3.1-Kv3.4) represent a family of voltage-gated K(+) channels that have fast-spiking properties. Kv3.1 channel subunits are predominantly localized to cortical parvalbumin (PV)-positive, inhibitory interneurons. The firing properties of these interneurons participate in establishing the normal gamma oscillations and synchrony of cortical neuronal populations, thought to be the signature of higher information processing in human brain. Schizophrenia (SZ) is associated with abnormalities in cortical gamma synchrony and in information processing, particularly with dysfunction in working memory and executive function. Here, we report the distribution of Kv3.1b and Kv3.2 protein in normal human brain, showing that Kv3.1b is limited to neocortical areas, whereas Kv3.2 is abundantly represented in neo- and subcortical regions. In SZ cases, levels of Kv3.1b protein are decreased in the neocortex, but only in cases without antipsychotic drug (APD) treatment; Kv3.1 levels are normal in antipsychotic-treated cases. Kv3.2 is not different in distribution or in level between normal and SZ cases, nor influenced by APD, in any region tested. The apparent increase in Kv3.1b protein levels by APDs in SZ neocortex was confirmed in laboratory rodents treated with chronic APDs. These findings show a decrease in Kv3.1b channel protein in SZ neocortex, a deficit that is restored by APDs. This alteration could be fundamentally involved in the cortical manifestations of SZ and in the therapeutic response to APDs.

  10. T Cell Subset and Stimulation Strength-Dependent Modulation of T Cell Activation by Kv1.3 Blockers

    PubMed Central

    Fung-Leung, Wai-Ping; Edwards, Wilson; Liu, Yi; Ngo, Karen; Angsana, Julianty; Castro, Glenda; Wu, Nancy; Liu, Xuejun; Swanson, Ronald V.; Wickenden, Alan D.

    2017-01-01

    Kv1.3 is a voltage-gated potassium channel expressed on T cells that plays an important role in T cell activation. Previous studies have shown that blocking Kv1.3 channels in human T cells during activation results in reduced calcium entry, cytokine production, and proliferation. The aim of the present study was to further explore the effects of Kv1.3 blockers on the response of different human T cell subsets under various stimulation conditions. Our studies show that, unlike the immune suppressor cyclosporine A, the inhibitory effect of Kv1.3 blockers was partial and stimulation strength dependent, with reduced inhibitory efficacy on T cells under strengthened anti-CD3/CD28 stimulations. T cell responses to allergens including house dust mites and ragweed were partially reduced by Kv1.3 blockers. The effect of Kv1.3 inhibition was dependent on T cell subsets, with stronger effects on CCR7- effector memory compared to CCR7+ central memory CD4 T cells. Calcium entry studies also revealed a population of CD4 T cells resistant to Kv1.3 blockade. Activation of CD4 T cells was accompanied with an increase in Kv1.3 currents but Kv1.3 transcripts were found to be reduced, suggesting a posttranscriptional mechanism in the regulation of Kv1.3 activities. In summary, Kv1.3 blockers inhibit T cell activation in a manner that is highly dependent on the T cell identity and stimulation strength, These findings suggest that Kv1.3 blockers inhibit T cells in a unique, conditional manner, further refining our understanding of the therapeutic potential of Kv1.3 blockers. PMID:28107393

  11. Modulation of Kv3 Subfamily Potassium Currents by the Sea Anemone Toxin BDS: Significance for CNS and Biophysical Studies

    PubMed Central

    Yeung, Shuk Yin M.; Thompson, Dawn; Wang, Zhuren; Fedida, David; Robertson, Brian

    2005-01-01

    Kv3 potassium channels, with their ultra-rapid gating and high activation threshold, are essential for high-frequency firing in many CNS neurons. Significantly, the Kv3.4 subunit has been implicated in the major CNS disorders Parkinson’s and Alzheimer’s diseases, and it is claimed that selectively targeting this subunit will have therapeutic utility. Previous work suggested that BDS toxins (“blood depressing substance,” from the sea anemone Anemonia sulcata) were specific blockers for rapidly inactivating Kv3.4 channels, and consequently these toxins are increasingly used as diagnostic agents for Kv3.4 subunits in central neurons. However, precisely how selective are these toxins for this important CNS protein? We show that BDS is not selective for Kv3.4 but markedly inhibits current through Kv3.1 and Kv3.2 channels. Inhibition comes about not by “pore block” but by striking modification of Kv3 gating kinetics and voltage dependence. Activation and inactivation kinetics are slowed by BDS-I and BDS-II, and V1/2 for activation is shifted to more positive voltages. Alanine substitution mutagenesis around the S3b and S4 segments of Kv3.2 reveals that BDS acts via voltage-sensing domains, and, consistent with this, ON gating currents from nonconducting Kv3.2 are markedly inhibited. The altered kinetics and gating properties, combined with lack of subunit selectivity with Kv3 subunits, seriously affects the usefulness of BDS toxins in CNS studies. Furthermore, our results do not easily fit with the voltage sensor “paddle” structure proposed recently for Kv channels. Our data will be informative for experiments designed to dissect out the roles of Kv3 subunits in CNS function and dysfunction. PMID:16177043

  12. Cell Type Specific Spatial and Functional Coupling Between Mammalian Brain Kv2.1 K+ Channels and Ryanodine Receptors

    PubMed Central

    Mandikian, Danielle; Bocksteins, Elke; Parajuli, Laxmi Kumar; Bishop, Hannah I.; Cerda, Oscar; Shigemoto, Ryuichi; Trimmer, James S.

    2014-01-01

    The Kv2.1 voltage-gated K+ channel is widely expressed throughout mammalian brain where it contributes to dynamic activity-dependent regulation of intrinsic neuronal excitability. Here we show that somatic plasma membrane Kv2.1 clusters are juxtaposed to clusters of intracellular ryanodine receptor (RyR) Ca2+-release channels in mouse brain neurons, most prominently in medium spiny neurons (MSNs) of the striatum. Electron microscopy-immunogold labeling shows that in MSNs, plasma membrane Kv2.1 clusters are adjacent to subsurface cisternae, placing Kv2.1 in close proximity to sites of RyR-mediated Ca2+ release. Immunofluorescence labeling in transgenic mice expressing GFP in specific MSN populations reveals the most prominent juxtaposed Kv2.1-RyR clusters in indirect pathway MSNs. Kv2.1 in both direct and indirect pathway MSNs exhibits markedly lower levels of labeling with phosphospecific antibodies directed against the S453, S563, and S603 phosphorylation site compared to levels observed in neocortical neurons, although labeling for Kv2.1 phosphorylation at S563 was significantly lower in indirect pathway MSNs compared to those in the direct pathway. Finally, acute stimulation of RyRs in heterologous cells causes a rapid hyperpolarizing shift in the voltage-dependence of activation of Kv2.1, typical of Ca2+/calcineurin-dependent Kv2.1 dephosphorylation. Together, these studies reveal that striatal MSNs are distinct in their expression of clustered Kv2.1 at plasma membrane sites juxtaposed to intracellular RyRs, as well as in Kv2.1 phosphorylation state. Differences in Kv2.1 expression and phosphorylation between MSNs in direct and indirect pathways provide a cell- and circuit-specific mechanism for coupling intracellular Ca2+ release to phosphorylation-dependent regulation of Kv2.1 to dynamically impact intrinsic excitability. PMID:24962901

  13. PKC-DEPENDENT REGULATION OF Kv7.5 CHANNELS BY THE BRONCHOCONSTRICTOR HISTAMINE IN HUMAN AIRWAY SMOOTH MUSCLE CELLS.

    PubMed

    Haick, Jennifer M; Brueggemann, Lioubov I; Cribbs, Leanne L; Denning, Mitchell F; Schwartz, Jeffrey; Byron, Kenneth L

    2017-03-10

    Kv7 potassium channels have recently been found to be expressed and functionally important for relaxation of airway smooth muscle. Previous research suggests that native Kv7 currents are inhibited following treatment of freshly isolated airway smooth muscle cells with bronchoconstrictor agonists, and in intact airways inhibition of Kv7 channels is sufficient to induce bronchiolar constriction. However, the mechanism by which Kv7 currents are inhibited by bronchoconstrictor agonists has yet to be elucidated. In the present study, native Kv7 currents in cultured human trachealis smooth muscle cells (HTSMCs) were observed to be inhibited upon treatment with histamine; inhibition of Kv7 currents was associated with membrane depolarization and an increase in cytosolic Ca2+ ([Ca2+]cyt). The latter response was inhibited by verapamil, a blocker of L-type voltage sensitive Ca2+ channels (VSCCs). Protein kinase C (PKC) has been implicated as a mediator of bronchoconstrictor actions, though the targets of PKC are not clearly established. We found that histamine treatment significantly and dose-dependently suppressed currents through overexpressed wild-type human Kv7.5 (hKv7.5) channels in cultured HTSMCs, and this effect was inhibited by the PKC inhibitor Ro-31-8220 (3 µM). The PKC-dependent suppression of hKv7.5 currents corresponded with a PKC-dependent increase in hKv7.5 channel phosphorylation. Knocking down or inhibiting PKCα, or mutating hKv7.5 serine 441 to alanine, abolished the inhibitory effects of histamine on hKv7.5 currents. These findings provide the first evidence linking PKC activation to suppression of Kv7 currents, membrane depolarization, and Ca2+ influx via L-type VSCCs as a mechanism for histamine-induced bronchoconstriction.

  14. KChIPs and Kv4 alpha subunits as integral components of A-type potassium channels in mammalian brain.

    PubMed

    Rhodes, Kenneth J; Carroll, Karen I; Sung, M Amy; Doliveira, Lisa C; Monaghan, Michael M; Burke, Sharon L; Strassle, Brian W; Buchwalder, Lynn; Menegola, Milena; Cao, Jie; An, W Frank; Trimmer, James S

    2004-09-08

    Voltage-gated potassium (Kv) channels from the Kv4, or Shal-related, gene family underlie a major component of the A-type potassium current in mammalian central neurons. We recently identified a family of calcium-binding proteins, termed KChIPs (Kv channel interacting proteins), that bind to the cytoplasmic N termini of Kv4 family alpha subunits and modulate their surface density, inactivation kinetics, and rate of recovery from inactivation (An et al., 2000). Here, we used single and double-label immunohistochemistry, together with circumscribed lesions and coimmunoprecipitation analyses, to examine the regional and subcellular distribution of KChIPs1-4 and Kv4 family alpha subunits in adult rat brain. Immunohistochemical staining using KChIP-specific monoclonal antibodies revealed that the KChIP polypeptides are concentrated in neuronal somata and dendrites where their cellular and subcellular distribution overlaps, in an isoform-specific manner, with that of Kv4.2 and Kv4.3. For example, immunoreactivity for KChIP1 and Kv4.3 is concentrated in the somata and dendrites of hippocampal, striatal, and neocortical interneurons. Immunoreactivity for KChIP2, KChIP4, and Kv4.2 is concentrated in the apical and basal dendrites of hippocampal and neocortical pyramidal cells. Double-label immunofluorescence labeling revealed that throughout the forebrain, KChIP2 and KChIP4 are frequently colocalized with Kv4.2, whereas in cortical, hippocampal, and striatal interneurons, KChIP1 is frequently colocalized with Kv4.3. Coimmunoprecipitation analyses confirmed that all KChIPs coassociate with Kv4 alpha subunits in brain membranes, indicating that KChIPs 1-4 are integral components of native A-type Kv channel complexes and are likely to play a major role as modulators of somatodendritic excitability.

  15. [Kv3.4 channel is involved in rat pulmonary vasoconstriction induced by 15-hydroxyeicosatetraenoic acid].

    PubMed

    Li, Qian; Bi, Hai-Rong; Zhang, Rong; Zhu, Da-Ling

    2006-02-25

    We have reported that hypoxia increases the activation of 15-lipoxygenase (15-LO), which converts arachidonic acid (AA) into 15-hydroxyeicosatetraenoic acid (15-HETE) in small pulmonary arteries (PAs). Through inhibition of Kv channels, 15-HETE causes more robust concentration-dependent contraction of PA rings from the hypoxic compared to the normoxic controls. However, the subtypes of Kv channels inhibited by 15-HETE are incompletely understood. The aim of the present study was to identify the contribution of Kv3.4 channel in the process of pulmonary vasoconstriction induced by 15-HETE using the tension studies of PA rings from rat with Kv3.4 channel blocker in tissue bath; to explore the role of vascular endothelium in15-HETE-induced pulmonary vasoconstriction through denuded endothelia of PA rings; and to define the downregulation of 15-HETE on the expression of Kv3.4 channel in cultured pulmonary artery smooth muscle cells (PASMCs) with RT-PCR and Western blot. In the present study, healthy Wistar rats were divided randomly into two groups: Group A with normal oxygen supply and group B with hypoxia. Six days later, the rats were killed. Pulmonary artery rings were prepared for organ bath experiments. Firstly, different concentrations of 15-HETE (10~1 000 nmol/L) were added to the Krebs solution. The isometric tension was recorded using a four-channel force-displacement transducer. Then Kv3.4 channel blocker, 100 nmol/L BDS-I, was added, followed by adding 1 mumol/L 15-HETE, and the isometric tension was recorded. Furthermore, RT-PCR and Western blot were employed to identify the influence of 15-HETE on the expression of Kv3.4 channel in cultured rat PASMCs.The results showed the PA tension was significantly increased both in groups A and B by 15-HETE in a concentration-dependent manner (P<0.05), especially in group B (P<0.05 compared to control); denuded endothelia enhanced 15-HETE concentration-related constrictions in rat PA rings; Kv3.4 channel blocker, BDS

  16. Characterization of N-glycosylation consensus sequences in the Kv3.1 channel.

    PubMed

    Brooks, Natasha L; Corey, Melissa J; Schwalbe, Ruth A

    2006-07-01

    N-Glycosylation is a cotranslational and post-translational process of proteins that may influence protein folding, maturation, stability, trafficking, and consequently cell surface expression of functional channels. Here we have characterized two consensus N-glycosylation sequences of a voltage-gated K+ channel (Kv3.1). Glycosylation of Kv3.1 protein from rat brain and infected Sf9 cells was demonstrated by an electrophoretic mobility shift assay. Digestion of total brain membranes with peptide N glycosidase F (PNGase F) produced a much faster-migrating Kv3.1 immunoband than that of undigested brain membranes. To demonstrate N-glycosylation of wild-type Kv3.1 in Sf9 cells, cells were treated with tunicamycin. Also, partially purified proteins were digested with either PNGase F or endoglycosidase H. Attachment of simple-type oligosaccharides at positions 220 and 229 was directly shown by single (N229Q and N220Q) and double (N220Q/N229Q) Kv3.1 mutants. Functional measurements and membrane fractionation of infected Sf9 cells showed that unglycosylated Kv3.1s were transported to the plasma membrane. Unitary conductance of N220Q/N229Q was similar to that of the wild-type Kv3.1. However, whole cell currents of N220Q/N229Q channels had slower activation rates, and a slight positive shift in voltage dependence compared to wild-type Kv3.1. The voltage dependence of channel activation for N229Q and N220Q was much like that for N220Q/N229Q. These results demonstrate that the S1-S2 linker is topologically extracellular, and that N-glycosylation influences the opening of the voltage-dependent gate of Kv3.1. We suggest that occupancy of the sites is critical for folding and maturation of the functional Kv3.1 at the cell surface.

  17. Single Input Fuzzy Controller with Command Shaping Schemes for Double-Pendulum Overhead Crane

    NASA Astrophysics Data System (ADS)

    Ahmad, M. A.; Saealal, M. S.; Ismail, R. M. T. Raja; Zawawi, M. A.; Nasir, A. N. K.; Ramli, M. S.

    2011-06-01

    This paper presents investigations into the development of composite control schemes for trajectory tracking and anti-sway control of a double-pendulum-type overhead crane (DPTOC) system. A nonlinear DPTOC system is considered and the dynamic model of the system is derived using the Euler-Lagrange formulation. The proposed method, known as the Single Input Fuzzy Logic Controller (SIFLC), reduces the conventional two-input FLC (CFLC) to a single input single output (SISO) controller. The SIFLC is developed for position control of cart movement. This is then extended to incorporate input shaping schemes for anti-swaying control of the system. The input shapers with different mode selection are designed based on the properties of the system. The results of the response with the controllers are presented in time and frequency domains. The performances of control schemes are examined in terms of level of input tracking capability, sway angle reduction and time response specifications in comparison to SIFLC controller. Finally, a comparative assessment of the control techniques is discussed and presented.

  18. Multivariable time series prediction for the icing process on overhead power transmission line.

    PubMed

    Li, Peng; Zhao, Na; Zhou, Donghua; Cao, Min; Li, Jingjie; Shi, Xinling

    2014-01-01

    The design of monitoring and predictive alarm systems is necessary for successful overhead power transmission line icing. Given the characteristics of complexity, nonlinearity, and fitfulness in the line icing process, a model based on a multivariable time series is presented here to predict the icing load of a transmission line. In this model, the time effects of micrometeorology parameters for the icing process have been analyzed. The phase-space reconstruction theory and machine learning method were then applied to establish the prediction model, which fully utilized the history of multivariable time series data in local monitoring systems to represent the mapping relationship between icing load and micrometeorology factors. Relevant to the characteristic of fitfulness in line icing, the simulations were carried out during the same icing process or different process to test the model's prediction precision and robustness. According to the simulation results for the Tao-Luo-Xiong Transmission Line, this model demonstrates a good accuracy of prediction in different process, if the prediction length is less than two hours, and would be helpful for power grid departments when deciding to take action in advance to address potential icing disasters.

  19. Multivariable Time Series Prediction for the Icing Process on Overhead Power Transmission Line

    PubMed Central

    Li, Peng; Zhao, Na; Zhou, Donghua; Cao, Min; Li, Jingjie; Shi, Xinling

    2014-01-01

    The design of monitoring and predictive alarm systems is necessary for successful overhead power transmission line icing. Given the characteristics of complexity, nonlinearity, and fitfulness in the line icing process, a model based on a multivariable time series is presented here to predict the icing load of a transmission line. In this model, the time effects of micrometeorology parameters for the icing process have been analyzed. The phase-space reconstruction theory and machine learning method were then applied to establish the prediction model, which fully utilized the history of multivariable time series data in local monitoring systems to represent the mapping relationship between icing load and micrometeorology factors. Relevant to the characteristic of fitfulness in line icing, the simulations were carried out during the same icing process or different process to test the model's prediction precision and robustness. According to the simulation results for the Tao-Luo-Xiong Transmission Line, this model demonstrates a good accuracy of prediction in different process, if the prediction length is less than two hours, and would be helpful for power grid departments when deciding to take action in advance to address potential icing disasters. PMID:25136653

  20. Evaluation and treatment of internal impingement of the shoulder in overhead athletes

    PubMed Central

    Corpus, Keith T; Camp, Christopher L; Dines, David M; Altchek, David W; Dines, Joshua S

    2016-01-01

    One of the most common pathologic processes seen in overhead throwing athletes is posterior shoulder pain resulting from internal impingement. “Internal impingement” is a term used to describe a constellation of symptoms which result from the greater tuberosity of the humerus and the articular surface of the rotator cuff abutting the posterosuperior glenoid when the shoulder is in an abducted and externally rotated position. The pathophysiology in symptomatic internal impingement is multifactorial, involving physiologic shoulder remodeling, posterior capsular contracture, and scapular dyskinesis. Throwers with internal impingement may complain of shoulder stiffness or the need for a prolonged warm-up, decline in performance, or posterior shoulder pain. On physical examination, patients will demonstrate limited internal rotation and posterior shoulder pain with a posterior impingement test. Common imaging findings include the classic “Bennett lesion” on radiographs, as well as articular-sided partial rotator cuff tears and concomitant SLAP lesions. Mainstays of treatment include intense non-operative management focusing on rest and stretching protocols focusing on the posterior capsule. Operative management is variable depending on the exact pathology, but largely consists of rotator cuff debridement. Outcomes of operative treatment have been mixed, therefore intense non-operative treatment should remain the focus of treatment. PMID:28032029

  1. IDC: a system for automatically detecting and classifying manmade objects in overhead imagery

    NASA Astrophysics Data System (ADS)

    Carlotto, Mark J.; Nebrich, Mark; De Michael, David

    2010-04-01

    The automatic detection and classification of manmade objects in overhead imagery is key to generating geospatial intelligence (GEOINT) from today's high space-time bandwidth sensors in a timely manner. A flexible multi-stage object detection and classification capability known as the IMINT Data Conditioner (IDC) has been developed that can exploit different kinds of imagery using a mission-specific processing chain. A front-end data reader/tiler converts standard imagery products into a set of tiles for processing, which facilitates parallel processing on multiprocessor/multithreaded systems. The first stage of processing contains a suite of object detectors designed to exploit different sensor modalities that locate and chip out candidate object regions. The second processing stage segments object regions, estimates their length, width, and pose, and determines their geographic location. The third stage classifies detections into one of K predetermined object classes (specified in a models file) plus clutter. Detections are scored based on their salience, size/shape, and spatial-spectral properties. Detection reports can be output in a number of popular formats including flat files, HTML web pages, and KML files for display in Google Maps or Google Earth. Several examples illustrating the operation and performance of the IDC on Quickbird, GeoEye, and DCS SAR imagery are presented.

  2. Overhead spine arch analysis of dairy cows from three-dimensional video

    NASA Astrophysics Data System (ADS)

    Abdul Jabbar, K.; Hansen, M. F.; Smith, M. L.; Smith, L. N.

    2017-02-01

    We present a spine arch analysis method in dairy cows using overhead 3D video data. This method is aimed for early stage lameness detection. That is important in order to allow early treatment; and thus, reduce the animal suffering and minimize the high forecasted financial losses, caused by lameness. Our physical data collection setup is non-intrusive, covert and designed to allow full automation; therefore, it could be implemented on a large scale or daily basis with high accuracy. We track the animal's spine using shape index and curvedness measure from the 3D surface as she walks freely under the 3D camera. Our spinal analysis focuses on the thoracic vertebrae region, where we found most of the arching caused by lameness. A cubic polynomial is fitted to analyze the arch and estimate the locomotion soundness. We have found more accurate results by eliminating the regular neck/head movements' effect from the arch. Using 22-cow data set, we are able to achieve an early stage lameness detection accuracy of 95.4%.

  3. Detailed side and overhead views of geologic features from joint panoramic and blimp operations

    SciTech Connect

    Chase, T.E.; Young, J.D. )

    1990-06-01

    A portion of the California coast, including the Loma Prieta earthquake damage at Moss Landing, is shown with the topography displayed from side and overhead viewing angles. This technique offers a different approach to mapping shorelines and studying the oceanographic forces creating and shaping these geologic features. Two pieces of equipment were developed to create these views. The first is a panoramic camera with viewing angles up to 360{degree} and two telephoto settings (70mm and 210mm) allowing a feature to be photographed from the same point with different lens magnifications. The second is a 20 ft helium-filled blimp with 35mm cameras mounted in a tray with a radio control receiver triggering the camera shutters after receiving a signal transmitted from a person on the ground. Video camcorders can also be carried. Tethered to the person on the ground, the blimp's height is determined by the amount of line payed out. Horizontal movement of the blimp is controlled by the operator walking or riding slowly in a boat or truck. The blimp can be flown at different elevations, remain in a stationary position for time-lapse photographs, or be moved about to prepare a mosaic of the area. Both systems can be used in remote areas because they are portable and the power supplies needed to operate are from lightweight batteries.

  4. Position Estimation Verification Testing for the Video Guidance Sensor and Dynamic Overhead Target Simulator

    NASA Technical Reports Server (NTRS)

    Gaines, Joseph; Johnston, Nick

    1999-01-01

    The Video Guidance Sensor, part of the Automated Rendezvous and Capture mechanism, is due to undergo formal qualification testing at Marshall Space Flight Center. Before it undergoes this qualification, a test was needed to verify repeatability of the sensor, and to allow different sensor configurations to be compared. This test was developed at the Flight Robotics Laboratory. The test uses a software script to drive the sensor target to the same position and thus allows sensor runs to be compared. The sensor target is the Dynamic Overhead Target Simulator. The simulator uses encoders as its position indicator. Distance Measuring Device's were used to independently verify the software script, the sensor reading, and the target position. The test area, sensor, and other test equipment are briefly described. The actual data is tabulated and will serve as a baseline for future tests. The software script was found to be adequate for the test. Position repeatability was acceptable for all the equipment. The system test is now ready to be used in formal qualification testing.

  5. Syntaxin 1A binds to the cytoplasmic C terminus of Kv2.1 to regulate channel gating and trafficking.

    PubMed

    Leung, Yuk M; Kang, Youhou; Gao, Xiaodong; Xia, Fuzhen; Xie, Huanli; Sheu, Laura; Tsuk, Sharon; Lotan, Ilana; Tsushima, Robert G; Gaisano, Herbert Y

    2003-05-09

    Voltage-gated K(+) (Kv) 2.1 is the dominant Kv channel that controls membrane repolarization in rat islet beta-cells and downstream insulin exocytosis. We recently showed that exocytotic SNARE protein SNAP-25 directly binds and modulates rat islet beta-cell Kv 2.1 channel protein at the cytoplasmic N terminus. We now show that SNARE protein syntaxin 1A (Syn-1A) binds and modulates rat islet beta-cell Kv2.1 at its cytoplasmic C terminus (Kv2.1C). In HEK293 cells overexpressing Kv2.1, we observed identical effects of channel inhibition by dialyzed GST-Syn-1A, which could be blocked by Kv2.1C domain proteins (C1: amino acids 412-633, C2: amino acids 634-853), but not the Kv2.1 cytoplasmic N terminus (amino acids 1-182). This was confirmed by direct binding of GST-Syn-1A to the Kv2.1C1 and C2 domains proteins. These findings are in contrast to our recent report showing that Syn-1A binds and modulates the cytoplasmic N terminus of neuronal Kv1.1 and not by its C terminus. Co-expression of Syn-1A in Kv2.1-expressing HEK293 cells inhibited Kv2.1 surfacing, which caused a reduction of Kv2.1 current density. In addition, Syn-1A caused a slowing of Kv2.1 current activation and reduction in the slope factor of steady-state inactivation, but had no affect on inactivation kinetics or voltage dependence of activation. Taken together, SNAP-25 and Syn-1A mediate secretion not only through its participation in the exocytotic SNARE complex, but also by regulating membrane potential and calcium entry through their interaction with Kv and Ca(2+) channels. In contrast to Ca(2+) channels, where these SNARE proteins act on a common synprint site, the SNARE proteins act not only on distinct sites within a Kv channel, but also on distinct sites between different Kv channel families.

  6. Retigabine, a Kv7.2/Kv7.3-Channel Opener, Attenuates Drug-Induced Seizures in Knock-In Mice Harboring Kcnq2 Mutations

    PubMed Central

    Ihara, Yukiko; Tomonoh, Yuko; Deshimaru, Masanobu; Zhang, Bo; Uchida, Taku; Ishii, Atsushi; Hirose, Shinichi

    2016-01-01

    The hetero-tetrameric voltage-gated potassium channel Kv7.2/Kv7.3, which is encoded by KCNQ2 and KCNQ3, plays an important role in limiting network excitability in the neonatal brain. Kv7.2/Kv7.3 dysfunction resulting from KCNQ2 mutations predominantly causes self-limited or benign epilepsy in neonates, but also causes early onset epileptic encephalopathy. Retigabine (RTG), a Kv7.2/ Kv7.3-channel opener, seems to be a rational antiepileptic drug for epilepsies caused by KCNQ2 mutations. We therefore evaluated the effects of RTG on seizures in two strains of knock-in mice harboring different Kcnq2 mutations, in comparison to the effects of phenobarbital (PB), which is the first-line antiepileptic drug for seizures in neonates. The subjects were heterozygous knock-in mice (Kcnq2Y284C/+ and Kcnq2A306T/+) bearing the Y284C or A306T Kcnq2 mutation, respectively, and their wild-type (WT) littermates, at 63–100 days of age. Seizures induced by intraperitoneal injection of kainic acid (KA, 12mg/kg) were recorded using a video-electroencephalography (EEG) monitoring system. Effects of RTG on KA-induced seizures of both strains of knock-in mice were assessed using seizure scores from a modified Racine’s scale and compared with those of PB. The number and total duration of spike bursts on EEG and behaviors monitored by video recording were also used to evaluate the effects of RTG and PB. Both Kcnq2Y284C/+ and Kcnq2A306T/+ mice showed significantly more KA-induced seizures than WT mice. RTG significantly attenuated KA-induced seizure activities in both Kcnq2Y284C/+ and Kcnq2A306T/+ mice, and more markedly than PB. This is the first reported evidence of RTG ameliorating KA-induced seizures in knock-in mice bearing mutations of Kcnq2, with more marked effects than those observed with PB. RTG or other Kv7.2-channel openers may be considered as first-line antiepileptic treatments for epilepsies resulting from KCNQ2 mutations. PMID:26910900

  7. Kv3.1-Kv3.2 channels underlie a high-voltage-activating component of the delayed rectifier K+ current in projecting neurons from the globus pallidus.

    PubMed

    Hernández-Pineda, R; Chow, A; Amarillo, Y; Moreno, H; Saganich, M; Vega-Saenz de Miera, E C; Hernández-Cruz, A; Rudy, B

    1999-09-01

    The globus pallidus plays central roles in the basal ganglia circuitry involved in movement control as well as in cognitive and emotional functions. There is therefore great interest in the anatomic and electrophysiological characterization of this nucleus. Most pallidal neurons are GABAergic projecting cells, a large fraction of which express the calcium binding protein parvalbumin (PV). Here we show that PV-containing pallidal neurons coexpress Kv3. 1 and Kv3.2 K+ channel proteins and that both Kv3.1 and Kv3.2 antibodies coprecipitate both channel proteins from pallidal membrane extracts solubilized with nondenaturing detergents, suggesting that the two channel subunits are forming heteromeric channels. Kv3.1 and Kv3.2 channels have several unusual electrophysiological properties when expressed in heterologous expression systems and are thought to play special roles in neuronal excitability including facilitating sustained high-frequency firing in fast-spiking neurons such as interneurons in the cortex and the hippocampus. Electrophysiological analysis of freshly dissociated pallidal neurons demonstrates that these cells have a current that is nearly identical to the currents expressed by Kv3.1 and Kv3.2 proteins in heterologous expression systems, including activation at very depolarized membrane potentials (more positive than -10 mV) and very fast deactivation rates. These results suggest that the electrophysiological properties of native channels containing Kv3.1 and Kv3.2 proteins in pallidal neurons are not significantly affected by factors such as associated subunits or postranslational modifications that result in channels having different properties in heterologous expression systems and native neurons. Most neurons in the globus pallidus have been reported to fire sustained trains of action potentials at high-frequency. Kv3.1-Kv3.2 voltage-gated K+ channels may play a role in helping maintain sustained high-frequency repetitive firing as they probably do

  8. Kv1.3 in Psoriatic Disease: PAP-1, a small molecule inhibitor of Kv1.3 is effective in the SCID mouse psoriasis - xenograft model

    PubMed Central

    Kundu-Raychaudhuri, Smriti; Chen, Yi-Je; Wulff, Heike; Raychaudhuri, Siba P

    2015-01-01

    Kv1.3 channels regulate the activation/proliferation of effector memory T cells and thus play a critical role in the pathogenesis of autoimmune diseases. Using a combination of immunohistochemistry, confocal microscopy, flow cytometry and electrophysiology methods we observed a significant enrichment of activated Kv1.3+ memory T cells in psoriasis plaques and synovial fluid from patients with psoriasis/psoriatic arthritis (PsA) compared to non-lesional psoriatic skin, normal skin or peripheral blood lympho-mononuclear cells. In in vitro studies performed with lesional mononuclear cells or T cells derived from skin and joints of psoriatic disease, the small molecule Kv1.3 blocker PAP-1 dose-dependently inhibited proliferation and suppressed IL-2 and IFN-γ production. To further substantiate the pathologic role of Kv1.3highTEM cells in psoriatic disease we tested whether PAP-1 is able to improve psoriatic disease pathology in the SCID mouse-psoriasis skin xenograft model. Following four weeks of daily treatment with 2% PAP-1 ointment we noticed about 50% reduction in the epidermal thickness (rete peg length) and the number of CD3+ lymphocytes/mm2 of dermis decreased by 85%. Vehicle treated and untreated plaques in contrast remained unchanged and showed no reduction in epidermis thickness and infiltrating CD3+ T cells and HLA-DR+ T cells. Based on these results we propose the development of Kv1.3 targeted topical immunotherapy for psoriasis and possibly for other inflammatory skin conditions, where effector memory T cells are involved in the pathogenesis. PMID:25175978

  9. Kv3 K+ channels enable burst output in rat cerebellar Purkinje cells.

    PubMed

    McKay, B E; Turner, R W

    2004-08-01

    The ability of cells to generate an appropriate spike output depends on a balance between membrane depolarizations and the repolarizing actions of K(+) currents. The high-voltage-activated Kv3 class of K(+) channels repolarizes Na(+) spikes to maintain high frequencies of discharge. However, little is known of the ability for these K(+) channels to shape Ca(2+) spike discharge or their ability to regulate Ca(2+) spike-dependent burst output. Here we identify the role of Kv3 K(+) channels in the regulation of Na(+) and Ca(2+) spike discharge, as well as burst output, using somatic and dendritic recordings in rat cerebellar Purkinje cells. Kv3 currents pharmacologically isolated in outside-out somatic membrane patches accounted for approximately 40% of the total K(+) current, were very fast and high voltage activating, and required more than 1 s to fully inactivate. Kv3 currents were differentiated from other tetraethylammonium-sensitive currents to establish their role in Purkinje cells under physiological conditions with current-clamp recordings. Dual somatic-dendritic recordings indicated that Kv3 channels repolarize Na(+) and Ca(2+) spikes, enabling high-frequency discharge for both types of cell output. We further show that during burst output Kv3 channels act together with large-conductance Ca(2+)-activated K(+) channels to ensure an effective coupling between Ca(2+) and Na(+) spike discharge by preventing Na(+) spike inactivation. By contributing significantly to the repolarization of Na(+) and especially Ca(2+) spikes, our data reveal a novel function for Kv3 K(+) channels in the maintenance of high-frequency burst output for cerebellar Purkinje cells.

  10. Open channel block of Kv3.1 currents by fluoxetine.

    PubMed

    Sung, Min Ji; Ahn, Hye Sook; Hahn, Sang June; Choi, Bok Hee

    2008-01-01

    The action of fluoxetine, a serotonin reuptake inhibitor, on the cloned neuronal rat Kv3.1 channels stably expressed in Chinese hamster ovary cells was investigated using the whole-cell patch-clamp technique. Fluoxetine reduced Kv3.1 whole-cell currents in a reversible, concentration-dependent manner, with an IC(50) value and a Hill coefficient of 13.4 muM and 1.4, respectively. Fluoxetine accelerated the decay rate of inactivation of Kv3.1 currents without modifying the kinetics of current activation. The inhibition increased steeply between 0 and +30 mV, which corresponded with the voltage range for channel opening. In the voltage range positive to +30 mV, inhibition displayed a weak voltage dependence, consistent with an electrical distance delta of 0.38. The binding (k(+1)) and dissociation (k(-1)) rate constants for fluoxetine-induced block of Kv3.1 were 5.7 microM(-1)s(-1) and 53.5 s(-1), respectively. The theoretical K(D) value derived by k(-1)/k(+1) yielded 9.3 microM. Fluoxetine did not affect the ion selectivity of Kv3.1. Fluoxetine slowed the deactivation time course, resulting in a tail crossover phenomenon when the tail currents, recorded in the presence and absence of fluoxetine, were superimposed. Inhibition of Kv3.1 by fluoxetine was use-dependent. The present results suggest that fluoxetine acts on Kv3.1 currents as an open-channel blocker.

  11. Determinants of frequency-dependent regulation of Kv1.2-containing potassium channels.

    PubMed

    Baronas, Victoria A; Yang, Runying; Vilin, Yury Y; Kurata, Harley T

    2016-01-01

    Voltage-gated potassium channels are important regulators of electrical excitation in many tissues, with Kv1.2 standing out as an essential contributor in the CNS. Genetic deletion of Kv1.2 invariably leads to early lethality in mice. In humans, mutations affecting Kv1.2 function are linked to epileptic encephalopathy and movement disorders. We have demonstrated that Kv1.2 is subject to a unique regulatory mechanism in which repetitive stimulation leads to dramatic potentiation of current. In this study, we explore the properties and molecular determinants of this use-dependent potentiation/activation. First, we examine how alterations in duty cycle (depolarization and repolarization/recovery times) affect the onset and extent of use-dependent activation. Also, we use trains of repetitive depolarizations to test the effects of a variety of Thr252 (S2-S3 linker) mutations on use-dependent activation. Substitutions of Thr with some sterically similar amino acids (Ser, Val, and Met, but not Cys) retain use-dependent activation, while bulky or charged amino acid substitutions eliminate use-dependence. Introduction of Thr at the equivalent position in other Kv1 channels (1.1, 1.3, 1.4), was not sufficient to transfer the phenotype. We hypothesize that use-dependent activation of Kv1.2 channels is mediated by an extrinsic regulator that binds preferentially to the channel closed state, with Thr252 being necessary but not sufficient for this interaction to alter channel function. These findings extend the conclusions of our recent demonstration of use-dependent activation of Kv1.2-containing channels in hippocampal neurons, by adding new details about the molecular mechanism underlying this effect.

  12. Marys Lake 69/115-kV transmission line upgrade and substation expansion projects

    SciTech Connect

    1996-05-01

    Western Area Power Administration (Western) and the Platte River Power Authority (Platte River) propose to upgrade portions of the existing electric transmission and substation system that serves the Town of Estes Park, Colorado. The existing transmission lines between the Estes Power Plant Switchyard and the Marys Lake Substation include a 115,000 volt (115-kV) line and 69,000 volt (69-kV) line. Approximately one mile is a double-circuit 115/69-kV line on steel lattice structures, and approximately two miles consists of separate single-circuit 115-kV and a 69-kV lines, constructed on wood H-Frame structures. Both lines were constructed in 1951 by the US Bureau of Reclamation. The existing transmission lines are on rights-of-way (ROW) that vary from 75 feet to 120 feet and are owned by Western. There are 48 landowners adjacent to the existing ROW. All of the houses were built adjacent to the existing ROW after the transmission lines were constructed. Upgrading the existing 69-kV transmission line between the Marys Lake Substation and the Estes Power Plant Switchyard to 115-kV and expanding the Marys Lake Substation was identified as the most effective way in which to improve electric service to Estes Park. The primary purpose and need of the proposed project is to improve the reliability of electric service to the Town of Estes Park. Lack of reliability has been a historical concern, and reliability will always be less than desired until physical improvements are made to the electrical facilities serving Estes Park.

  13. Tityustoxin-K(alpha) blockade of the voltage-gated potassium channel Kv1.3

    PubMed Central

    Rodrigues, Aldo Rogelis A; Arantes, Eliane C; Monje, Francisco; Stuhmer, Walter; Varanda, Wamberto Antonio

    2003-01-01

    We investigated the action of TsTX-Kα on cloned Kv1.3 channels of the Shaker subfamily of voltage-gated potassium channels, using the voltage–clamp technique. Highly purified TsTX-Kα was obtained from the venom of the Brazilian scorpion Tityus serrulatus using a new purification protocol. Our results show that TsTX-Kα blocks Kv1.3 with high affinity in two expression systems. TsTX-Kα blockade of Kv1.3 channels expressed in Xenopus oocytes was found to be completely reversible and to exhibit a pH dependence. The KD was 3.9 nM at pH 7.5, 9.5 nM at pH 7.0 and 94.5 nM at pH 6.5. The blocking properties of TsTX-Kα in a mammalian cell line (L929), stably transfected to express Kv1.3, were studied using the patch–clamp technique. In this preparation, the toxin had a KD of 19.8 nM at pH 7.4. TsTX-Kα was found to affect neither the voltage-dependence of activation, nor the activation and deactivation time constants. The block appeared to be independent of the transmembrane voltage and the toxin did not interfere with the C-type inactivation process. Taken as a whole, our findings indicate that TsTX-Kα acts as a simple blocker of Kv1.3 channels. It is concluded that this toxin is a useful tool for probing not only the physiological roles of Kv1.2, but also those mediated by Kv1.3 channels. PMID:12871837

  14. Effects of dapoxetine on cloned Kv1.5 channels expressed in CHO cells.

    PubMed

    Jeong, Imju; Yoon, Shin Hee; Hahn, Sang June

    2012-07-01

    The effects of dapoxetine were examined on cloned Kv1.5 channels stably expressed in Chinese hamster ovary cells using the whole-cell patch clamp technique. Dapoxetine decreased the peak amplitude of Kv1.5 currents and accelerated the decay rate of current inactivation in a concentration-dependent manner with an IC ( 50 ) of 11.6 μM. Kinetic analysis of the time-dependent effects of dapoxetine on Kv1.5 current decay yielded the apparent association (k (+1 )) and dissociation (k (-1 )) rate constants of 2.8 μM(-1) s(-1) and 34.2 s(-1), respectively. The theoretical K ( D ) value, derived by k (-1 )/k (+1 ), yielded 12.3 μM, which was reasonably similar to the IC ( 50 ) value obtained from the concentration-response curve. Dapoxetine decreased the tail current amplitude and slowed the deactivation process of Kv1.5, which resulted in a tail crossover phenomenon. The block by dapoxetine is voltage-dependent and steeply increased at potentials between -10 and +10 mV, which correspond to the voltage range of channel activation. At more depolarized potentials, a weaker voltage dependence was observed (δ=0.31). Dapoxetine had no effect on the steady-state activation of Kv1.5 but shifted the steady-state inactivation curves in a hyperpolarizing direction. Dapoxetine produced a use-dependent block of Kv1.5 at frequencies of 1 and 2 Hz and slowed the time course for recovery of inactivation. These effects were reversible after washout of the drug. Our results indicate that dapoxetine blocks Kv1.5 currents by interacting with the channel in both the open and inactivated states of the channel.

  15. A Novel Modulator of Kv3 Potassium Channels Regulates the Firing of Parvalbumin-Positive Cortical Interneurons.

    PubMed

    Rosato-Siri, Marcelo D; Zambello, Erika; Mutinelli, Chiara; Garbati, Nicoletta; Benedetti, Roberto; Aldegheri, Laura; Graziani, Francesca; Virginio, Caterina; Alvaro, Giuseppe; Large, Charles H

    2015-09-01

    Kv3.1 and Kv3.2 high voltage-activated potassium channels, which display fast activation and deactivation kinetics, are known to make a crucial contribution to the fast-spiking phenotype of certain neurons. Pharmacological experiments show that the blockade of native Kv3 currents with low concentrations of tetraethylammonium or 4-aminopyridine impairs the expression of this firing phenotype. In particular, Kv3 channels are highly expressed by fast-spiking, parvalbumin-positive interneurons in corticolimbic brain circuits, which modulate the synchronization of cortical circuits and the generation of brain rhythms. Here, we describe a novel small molecule, (5R)-5-ethyl-3-(6-{[4-methyl-3-(methyloxy)phenyl]oxy}-3-pyridinyl)-2,4-imidazolidinedione (AUT1), which modulates Kv3.1 and Kv3.2 channels in human recombinant and rodent native neurons. AUT1 increased whole currents mediated by human Kv3.1b and Kv3.2a channels, with a concomitant leftward shift in the voltage dependence of activation. A less potent effect was observed on hKv3.3 currents. In mouse somatosensory cortex slices in vitro, AUT1 rescued the fast-spiking phenotype of parvalbumin-positive-fast-spiking interneurons following an impairment of their firing capacity by blocking a proportion of Kv3 channels with a low concentration of tetraethylammonium. Notably, AUT1 had no effect on interneuron firing when applied alone. Together, these data confirm the role played by Kv3 channels in the regulation of the firing phenotype of somatosensory interneurons and suggest that AUT1 and other Kv3 modulators could represent a new and promising therapeutic approach to the treatment of disorders associated with dysfunction of inhibitory feedback in corticolimbic circuits, such as schizophrenia.

  16. Improved Functional Expression of Human Cardiac Kv1.5 Channels and Trafficking-Defective Mutants by Low Temperature Treatment

    PubMed Central

    Toyoda, Futoshi; Matsuura, Hiroshi

    2014-01-01

    We herein investigated the effect of low temperature exposure on the expression, degradation, localization and activity of human Kv1.5 (hKv1.5). In hKv1.5-expressing CHO cells, the currents were significantly increased when cultured at a reduced temperature (28°C) compared to those observed at 37°C. Western blot analysis indicated that the protein levels (both immature and mature proteins) of hKv1.5 were significantly elevated under the hypothermic condition. Treatment with a proteasome inhibitor, MG132, significantly increased the immature, but not the mature, hKv1.5 protein at 37°C, however, there were no changes in either the immature or mature hKv1.5 proteins at low temperature following MG132 exposure. These observations suggest that the enhancement of the mature hKv1.5 protein at reduced temperature may not result from the inhibition of proteolysis. Moreover, the hKv1.5 fluorescence signal in the cells increased significantly on the cell surface at 28°C versus those cultured at 37°C. Importantly, the low temperature treatment markedly shifted the subcellular distribution of the mature hKv1.5, which showed considerable overlap with the trans-Golgi component. Experiments using tunicamycin, an inhibitor of N-glycosylation, indicated that the N-glycosylation of hKv1.5 is more effective at 28°C than at 37°C. Finally, the hypothermic treatment also rescued the protein expression and currents of trafficking-defective hKv1.5 mutants. These results indicate that low temperature exposure stabilizes the protein in the cellular organelles or on the plasma membrane, and modulates its maturation and trafficking, thus enhancing the currents of hKv1.5 and its trafficking defect mutants. PMID:24663680

  17. Positive Allosteric Modulation of Kv Channels by Sevoflurane: Insights into the Structural Basis of Inhaled Anesthetic Action

    PubMed Central

    Liang, Qiansheng; Anderson, Warren D.; Jones, Shelly T.; Souza, Caio S.; Hosoume, Juliana M.; Treptow, Werner; Covarrubias, Manuel

    2015-01-01

    Inhalational general anesthesia results from the poorly understood interactions of haloethers with multiple protein targets, which prominently includes ion channels in the nervous system. Previously, we reported that the commonly used inhaled anesthetic sevoflurane potentiates the activity of voltage-gated K+ (Kv) channels, specifically, several mammalian Kv1 channels and the Drosophila K-Shaw2 channel. Also, previous work suggested that the S4-S5 linker of K-Shaw2 plays a role in the inhibition of this Kv channel by n-alcohols and inhaled anesthetics. Here, we hypothesized that the S4-S5 linker is also a determinant of the potentiation of Kv1.2 and K-Shaw2 by sevoflurane. Following functional expression of these Kv channels in Xenopus oocytes, we found that converse mutations in Kv1.2 (G329T) and K-Shaw2 (T330G) dramatically enhance and inhibit the potentiation of the corresponding conductances by sevoflurane, respectively. Additionally, Kv1.2-G329T impairs voltage-dependent gating, which suggests that Kv1.2 modulation by sevoflurane is tied to gating in a state-dependent manner. Toward creating a minimal Kv1.2 structural model displaying the putative sevoflurane binding sites, we also found that the positive modulations of Kv1.2 and Kv1.2-G329T by sevoflurane and other general anesthetics are T1-independent. In contrast, the positive sevoflurane modulation of K-Shaw2 is T1-dependent. In silico docking and molecular dynamics-based free-energy calculations suggest that sevoflurane occupies distinct sites near the S4-S5 linker, the pore domain and around the external selectivity filter. We conclude that the positive allosteric modulation of the Kv channels by sevoflurane involves separable processes and multiple sites within regions intimately involved in channel gating. PMID:26599217

  18. Positive Allosteric Modulation of Kv Channels by Sevoflurane: Insights into the Structural Basis of Inhaled Anesthetic Action.

    PubMed

    Liang, Qiansheng; Anderson, Warren D; Jones, Shelly T; Souza, Caio S; Hosoume, Juliana M; Treptow, Werner; Covarrubias, Manuel

    2015-01-01

    Inhalational general anesthesia results from the poorly understood interactions of haloethers with multiple protein targets, which prominently includes ion channels in the nervous system. Previously, we reported that the commonly used inhaled anesthetic sevoflurane potentiates the activity of voltage-gated K+ (Kv) channels, specifically, several mammalian Kv1 channels and the Drosophila K-Shaw2 channel. Also, previous work suggested that the S4-S5 linker of K-Shaw2 plays a role in the inhibition of this Kv channel by n-alcohols and inhaled anesthetics. Here, we hypothesized that the S4-S5 linker is also a determinant of the potentiation of Kv1.2 and K-Shaw2 by sevoflurane. Following functional expression of these Kv channels in Xenopus oocytes, we found that converse mutations in Kv1.2 (G329T) and K-Shaw2 (T330G) dramatically enhance and inhibit the potentiation of the corresponding conductances by sevoflurane, respectively. Additionally, Kv1.2-G329T impairs voltage-dependent gating, which suggests that Kv1.2 modulation by sevoflurane is tied to gating in a state-dependent manner. Toward creating a minimal Kv1.2 structural model displaying the putative sevoflurane binding sites, we also found that the positive modulations of Kv1.2 and Kv1.2-G329T by sevoflurane and other general anesthetics are T1-independent. In contrast, the positive sevoflurane modulation of K-Shaw2 is T1-dependent. In silico docking and molecular dynamics-based free-energy calculations suggest that sevoflurane occupies distinct sites near the S4-S5 linker, the pore domain and around the external selectivity filter. We conclude that the positive allosteric modulation of the Kv channels by sevoflurane involves separable processes and multiple sites within regions intimately involved in channel gating.

  19. Pore mutants of HERG and KvLQT1 downregulate the reciprocal currents in stable cell lines

    PubMed Central

    Ren, Xiao-Qin; Liu, Gong Xin; Organ-Darling, Louise E.; Zheng, Renjian; Roder, Karim; Jindal, Hitesh K.; Centracchio, Jason; McDonald, Thomas V.

    2010-01-01

    We previously reported a transgenic rabbit model of long QT syndrome based on overexpression of pore mutants of repolarizing K+ channels KvLQT1 (LQT1) and HERG (LQT2).The transgenes in these rabbits eliminated the slow and fast components of the delayed rectifier K+ current (IKs and IKr, respectively), as expected. Interestingly, the expressed pore mutants of HERG and KvLQT1 downregulated the remaining reciprocal repolarizing currents, IKs and IKr, without affecting the steady-state levels of the native polypeptides. Here, we sought to further explore the functional interactions between HERG and KvLQT1 in heterologous expression systems. Stable Chinese hamster ovary (CHO) cell lines expressing KvLQT1-minK or HERG were transiently transfected with expression vectors coding for mutant or wild-type HERG or KvLQT1. Transiently expressed pore mutant or wild-type KvLQT1 downregulated IKr in HERG stable CHO cell lines by 70% and 44%, respectively. Immunostaining revealed a severalfold lower surface expression of HERG, which could account for the reduction in IKr upon KvLQT1 expression. Deletion of the KvLQT1 NH2-terminus did not abolish the downregulation, suggesting that the interactions between the two channels are mediated through their COOH-termini. Similarly, transiently expressed HERG reduced IKs in KvLQT1-minK stable cells. Coimmunoprecipitations indicated a direct interaction between HERG and KvLQT1, and surface plasmon resonance analysis demonstrated a specific, physical association between the COOH-termini of KvLQT1 and HERG. Here, we present an in vitro model system consistent with the in vivo reciprocal downregulation of repolarizing currents seen in transgenic rabbit models, illustrating the importance of the transfection method when studying heterologous ion channel expression and trafficking. Moreover, our data suggest that interactions between KvLQT1 and HERG are mediated through COOH-termini. PMID:20833965

  20. Validation of the Algorithm for Base Maintenance Overhead Costs for the Component Support Cost System (D160B).

    DTIC Science & Technology

    2014-09-26

    FOR I BASE MAINTENANCE OVERHEAD COSTS FOR THE COMPONENT SUPPORT COST SYSTEM (D160B) Contract No. F33600-82-C-0543 DTIC 13 December 1983 S ELECTED JUL 1...PREFIXES SRD Prefix Definition A-- Aircraft and Drones G-- Support Equipment H-- Precision Measurement Equipment N-- Air launched missiles and Guided...Missiles; Ground- O Launched Missiles; Except ICBMS; Drones ; and Related Training Equipment, 1 August 1976, updated to 15 October 1982 [221 TO-00-20-2-l0