Science.gov

Sample records for 500-kilovolt kv transmission

  1. 77 FR 53226 - Final Environmental Impact Statement for the Susquehanna to Roseland 500-kilovolt Transmission...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-31

    ... Transmission Line, Appalachian National Scenic Trail; Delaware Water Gap National Recreation Area and Middle...) transmission line to pass through three units of the National Park System: The Appalachian National Scenic... applicants. SUPPLEMENTARY INFORMATION: The Appalachian National Scenic Trail, Delaware Water Gap...

  2. 76 FR 15970 - Central Ferry to Lower Monumental 500-kilovolt Transmission Line Project

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-22

    ... AGENCY: Bonneville Power Administration (BPA), Department of Energy (DOE). ACTION: Notice of Availability..., and Walla Walla counties, Washington. BPA has decided to implement the Combination A Alternative... single- circuit transmission line from BPA's new Central Ferry Substation near the Port of Central...

  3. Engineering analysis of electrical effects for the COTP 500KV transmission line and EBMUD aqueduct corridor

    SciTech Connect

    Lewis, O.C.; Bell, G.K.; Ma, J.

    1995-12-31

    A study was conducted to determine AC electrical interference effects arising in the East Bay Municipal Utility District`s (EBMUD) Mokelumne Aqueducts due to their proximity to the Olinda-Tracy 500 kilovolt (kV) transmission line operated by the Western Area Power Administration (WESTERN). A six-wire gradient control wire mitigation system selected by EBMUD was modeled and evaluated. The study shows that the mitigation system performs satisfactorily under all conditions examined. During steady state conditions, touch voltages are maintained below 15 volts throughout the entire length of the three aqueducts. During fault conditions, touch voltages are maintained below 263 volts, the design limit calculated according to ANSI/IEEE Standard 80. The currents flowing through the isolator/surge protectors do not exceed the ratings of these devices, during steady state and fault conditions.

  4. 76 FR 72001 - Draft Environmental Impact Statement for the Susquehanna to Roseland 500-kilovolt Transmission Line

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-21

    ....gov , and can be viewed at the following locations: Eastern Monroe Public Library, 1002 North Ninth Street, Stroudsburg, PA 18360. Easton Area Public Library, 515 Church Street, Easton, PA 18042. Kemp Library East Stroudsburg University, Normal Street, East Stroudsburg, PA 18301. Pike County Public...

  5. Grand Coulee - Bell 500-kV Transmission Line Project, Draft Environmental Impact Statement

    SciTech Connect

    N /A

    2002-08-09

    BPA is proposing to construct a 500-kilovolt (kV) transmission line that would extend approximately 84 miles between the Grand Coulee 500-kV Switchyard, near Grand Coulee Dam, and the Bell Substation, in Mead just north of Spokane. The new line would cross portions of Douglas, Grant, Lincoln, and Spokane counties. In addition to the transmission line, new equipment would be installed at the substations at each end of the new line and at other facilities. The proposed action would remove an existing 115-kV transmission line and replace it with the new 500-kV line on existing right-of-way for most of its length. Additional right-of-way would be needed in the first 3.5 miles out of the Grand Coulee Switchyard to connect to the existing 115-kV right-of-way. Since the mid-1990s, the transmission path west of Spokane, called the West of Hatwai transmission pathway, has grown increasingly constrained. To date, BPA has been able to manage operation of the path through available operating practices, and customer needed have been met while maintaining the reliability of the path. however, in early 2001, operations showed that the amount of electricity that needs to flow from east to west along this path creates severe transmission congestion. Under these conditions, the system is at risk of overloads and violation of industry safety and reliability standards. The problem is particularly acute in the spring and summer months because of the large amount of power generated by dams east of the path. Large amounts of water cannot be spilled during that time in order for BPA to fulfill its obligation to protect threatened and endangered fish. The amount of power that needs to move through this area during these months at times could exceed the carrying capacity of the existing transmission lines. In additional capacity is not added, BPA will run a significant risk that it will not be able to continue to meet its contractual obligations to deliver power and maintain reliability

  6. 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)

  7. 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.

  8. 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

  9. 75 FR 56051 - Bemidji to Grand Rapids Minnesota 230 kV Transmission Line Project

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-15

    ...; ] DEPARTMENT OF AGRICULTURE Rural Utilities Service Bemidji to Grand Rapids Minnesota 230 kV Transmission Line... Rapids, Minnesota 230 kV Transmission Line Project (``Project'') in Minnesota. The Final EIS was prepared... application of Minnkota Power Cooperative, Inc. for RUS financing to construct a 230 kilovolt...

  10. 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

  11. Survey of Magnetic Fields Near BPA 230-kV and 500-kV Transmission Lines.

    SciTech Connect

    Perrin, Nancy; Aggarwal, Rajinder Pal; Bracken, T. Daniel

    1991-05-20

    The purpose of this study was to characterize typical levels and variability of 60Hz magnetic fields at the centerline and edge of right-of-way of Bonneville Power Administration (BPA) 230-kV and 500-kV transmission lines. This was accomplished by taking magnetic field measurements at over 800 spans in Oregon and Washington. The spans were sampled using a stratified random sampling procedure with region (East vs. West), voltage (230-kV vs 500-kV), and circuit configuration as strata. There were five different circuit configuration groups for each region/voltage category requiring a total of 200 strata. Magnetic field measurements were taken at 13 locations under each span using an EMDEX-C as a survey meter. Additional information recorded for each span included conductor height (at 10 locations), right-of-way width, longitudinal and lateral slope, time of day, vegetation, terrain, weather conditions, temperature, wind speed, span length and presence of other lines in the corridor. 9 refs., 17 figs., 26 tabs.

  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. Hayden-Blue River 345-kV transmission line project, Colorado

    SciTech Connect

    Not Available

    1982-09-01

    Tri-State Generation and Transmission Association, Inc., Colorado-Ute Electric Association, Inc., Platte River Power Authority, and Western Area Power Administration propose to construct and operate approximately 90 miles of 345-kilovolt (kV) transmission line between Hayden and the Blue River Valley in Colorado. The project would involve expansion of existing substation facilities at Hayden and construction of two new substations. The line would be operated at 230 kV initially. Estimated cost of the project is $37.8 million. The new line and substation facilities would provide a backup transmission path, satisfy the long-term needs in meeting the energy requirements, improve system reliability, improve system stability for the Craig and Hayden generating stations, and leave the existing 115-kV and 138-kV lines in operation to provide additional transmission capacity that would function as backup transmission during an outage on another line. Minute amounts of lands would be displaced. Construction activities would disturb critical ranges for elk and mule deer, elk calving areas, and the mating and nesting areas of greater sandhill cranes, great blue herons, sage grouse, golden eagles, and prairie falcons. Management of timberland would damage natural vegetation. The line would traverse 3.1 miles of flood-prone area, and as many as three transmission towers would lie within the floodplain of the Colorado River. The visual quality of land crossed by the line would be degraded somewhat.

  14. Lightning Surge Analysis for 500-kV Transmission Lines using Grounding Model with Dynamic Characteristics

    NASA Astrophysics Data System (ADS)

    Yasuda, Yoh; Kondo, Shuhei; Hara, Takehisa; Ikeda, Keiichi; Sonoi, Yasuo; Furuoka, Yoshihiro

    It is well known that grounding resistance under huge lightning current injection has current-dependent characteristics, whose mathematical model was already proposed by Liew and Darveniza in 1974. In this paper, where our final goal is reasonable design for lightning protection of 500-kV transmission tower, we adopt the dynamic grounding-resistance model to MODELS-ATP simulation. The effect of the model for the lightning surge analysis on 500-kV transmission line systems is discussed in detail.

  15. Design studies for the Mead-Phoenix 500 kV AC transmission project

    SciTech Connect

    Thallam, R.S.; Lundquist, T.G.; Gerlach, D.W.; Atmuri, S.R.; Selin, D.A.

    1995-10-01

    The Mead-Phoenix 500 kV ac line is 243 miles long and runs parallel to the existing Mead-Liberty 345 kV line. This line is planned for 70% series and 70% shunt compensation; it also incorporates the first application of a 50 kV phase shifting transformer that enables a 1,300 MW transmission capacity. This paper presents the design studies that were undertaken in arriving at the equipment ratings and insulation levels that lead to the equipment specifications. The shunt reactor switching requirements utilizing MOV across the breaker, line switching with line connected arresters and the breaker transient recovery voltage are also dealt with in the paper.

  16. 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.

  17. 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)

  18. AC and lightning performance of fiberglass crossarms aged in 115 kV transmission line

    SciTech Connect

    Grzybowski, S. . Dept. of Electrical and Computer Engineering); Jenkins, E.B. . Generation and Transmission Group)

    1993-10-01

    This paper presents the results of an investigation of the electrical performance of 115 kV transmission line fiberglass cross-arm used by Mississippi Power and Light Company. A transmission line fiberglass crossarm removed from service and companion cross-arms outdoors but not in service were examined. The evaluation of electrical performance was based on flashover voltage value at AC voltage and standard lightning impulses as well as under dry and wet conditions. The tests were performed in the Mississippi State University High Voltage Laboratory. The obtained flashover voltages show no large differences in electrical strength of fiberglass crossarms removed from service and those stored outdoors. The Added CFO voltage by fiberglass crossarm to the porcelain suspension insulators is presented versus the length of the fiberglass crossarm for dry and wet conditions.

  19. Weld-Windsor 115-kV Transmission Line Project, Weld County, Colorado

    SciTech Connect

    1996-05-01

    The Western Area Power Administration is proposing to rebuild a 3.0 mile segment of the existing Flatiron-Weld 115-kV transmission line in Weld County. The line would be reconductored with new conductor on new wood pole double circuit structures. The new structures would support a double circuit transmission line configuration. The first circuit would be owned by Western and the second by Public Service Company of Colorado (PSCO). Alternatives considered included no action, constructing PSCO`s circuit on new right-of-way, and reconductoring Western`s existing line on the same structures. The proposed action was selected because it provided an opportunity to share structures with PSCO and, overall, would minimize costs and environmental impacts. The environmental assessment identifies minor effects on existing natural or human resources and minor benefits for agricultural operations.

  20. Final environmental assessment: Los Reales 115 kV transmission line alternative routes

    SciTech Connect

    Not Available

    1989-10-01

    The Central Arizona Project (CAP) was authorized as a part of the Colorado River Basin Project Act (Public Law 90-537) on September 30, 1968. The primary purpose of the CAP is to furnish water for agricultural, municipal, and industrial uses in central and southern Arizona, and western New Mexico. Due to its magnitude, the CAP is divided into several major features serving separate but interrelated functions. The Tucson Aqueduct Phase B pumping plants were designed and constructed to operate on a looped power system. The entire looped power system, including two switching stations and connecting 115-kv transmission lines, was identified in the FEIS and approved for construction in the Secretary of Interior's Record of Decision dated September 24, 1985. The loop begins in the vicinity of the Twin Peaks Pumping Plant -- the northernmost Phase B pumping station, at the Rattlesnake Switching Station. All of the looped power system has been constructed with the exception of the switching station and portion of transmission line proposed to be constructed in this project. Without construction of this final portion of the looped power system, the Phase B pumping plants will not be able to operate normally without negatively affecting nearby power sources. The CAP will also not be able to provide the reliability necessary for municipal water systems dependent upon CAP water. The purpose of this EA is to describe impacts that would result from relocating the Los Reales 115-kV transmission line, and possibly the switching station, originally identified in the FEIS. It should be mentioned the Department of Energy will complete a separate NEPA review.

  1. New Waddell-Westwing 230-kV transmission project, Maricopa County, Arizona: Environmental assessment

    SciTech Connect

    Not Available

    1988-10-01

    The Western Area Power Administration (Western) proposes to construct a new 230 kilovolt (kV) transmission line in Maricopa County, Arizona, that would extend from the New Waddell Dam on the Agua Fria River, to the Westwing Substation, about 10.5 miles southwest of the dam. The project area is roughly 45 miles northwest of the Phoenix metropolitan area. Western will complete the National Environmental Policy Act of 1969 (NEPA) process for the line. A final environmental impact statement (EIS) was prepared by BuRec to describe the environmental impacts associated with alternatives for the construction and operation of the Regulatory Storage Division of the Central Arizona Project (CAP). The EIS was supported by 23 technical reports that covered planning, design, public involvement, social and environmental impact assessment, economics, and hydrological analysis. Since the proposed transmission system differs only slightly from that described in the EIS, Western incorporates by reference the EIS and its 23 supporting technical reports into this environmental assessment (EA). In August 1985, BuRec completed an EA on modifications to the New Waddell Dam Project design plans and issued a FONSI on these modifications; the EA did not cover the transmission line. The purpose of this EA is to document the potential environmental effects of the proposed construction of the transmission line and switchyards in order to determine if an EIS is needed or if a finding of no significant impact (FONSI) is indicated. 28 refs., 5 figs., 1 tab.

  2. Space charge drift from a +/- 400-kV direct current transmission line.

    PubMed

    Hendrickson, R C

    1986-01-01

    The Minnesota Environmental Quality Board completed a 3-year study of the space charge plume outside the right of way of a bipolar (+/- 400 kV) direct current transmission line in rural west central Minnesota. The purpose of the study was to determine the levels of DC potential gradient and small airs ions in the downwind plume to which humans and animals may be exposed. Potential gradient measurements show that a space charge plume is detectable downwind at least 1600 m from the transmission line. Plume relaxation rates indicate that under certain conditions one could detect the plume at twice that distance or more. Net charge in the plume assumes the polarity of the downwind energized transmission line conductor. The bipolar DC line thus electrically bisects the land through which it passes; on one side of the line there is a net positive space charge, on the other side a net negative space charge. Electric charge in the plume resides on aerosols and small air ions. Polar conductivity data substantiate the fact that small air ions of one polarity in the plume are elevated while those of opposite polarity are suppressed compared to background concentrations found in the rural environment. The resulting charge imbalance persists downwind at least 1600 m, though the median small air ion concentrations of plume polarity have adjusted to within the background range by that time with perpendicular wind speed components between 1 and 6 m/sec.

  3. Environmental Assessment of the Gering-Stegall 115-kV Transmission Line Consolidation Project, Scotts Bluff County, Nebraska

    SciTech Connect

    1995-05-01

    The Department of Energy (DOE), Western Area Power Administration (Western) proposes to consolidate segments of two transmission lines near the Gering Substation in Gering, Nebraska. The transmission lines are both located in Scotts Bluff County, Nebraska. The transmission lines are both located in Scotts Bluff County, Nebraska, within the city of Gering. Presently, there are three parallel 115-kilovolt (kV) transmission lines on separate rights-of-way (ROW) that terminate at the Gering Substation. The project would include dismantling the Archer-Gering wood-pole transmission line and rebuilding the remaining two lines on single-pole steel double circuit structures. The project would consolidate the Gering-Stegall North and Gering-Stegall South 115-kV transmission lines on to one ROW for a 1.33-mile segment between the Gering Substation and a point west of the Gering Landfill. All existing wood-pole H-frame structures would be removed, and the Gering-Stegall North and South ROWs abandoned. Western is responsible for the design, construction, operation, and maintenance of the line. Western prepared an environmental assessment (EA) that analyzed the potential environmental impacts of the proposed construction, operation, and maintenance of the 115-kV transmission line consolidation. Based on the analyses in the EA, the DOE finds that the proposed action is not a major Federal action significantly affecting the quality of the human environment, within the meaning of the National Environmental Policy Act of 1969 (NEPA).

  4. 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.

  5. Kv1.3 channels regulate synaptic transmission in the nucleus of solitary tract.

    PubMed

    Ramirez-Navarro, Angelina; Glazebrook, Patricia A; Kane-Sutton, Michelle; Padro, Caroline; Kline, David D; Kunze, Diana L

    2011-06-01

    The voltage-gated K(+) channel Kv1.3 has been reported to regulate transmitter release in select central and peripheral neurons. In this study, we evaluated its role at the synapse between visceral sensory afferents and secondary neurons in the nucleus of the solitary tract (NTS). We identified mRNA and protein for Kv1.3 in rat nodose ganglia using RT-PCR and Western blot analysis. In immunohistochemical experiments, anti-Kv1.3 immunoreactivity was very strong in internal organelles in the soma of nodose neurons with a weaker distribution near the plasma membrane. Anti-Kv1.3 was also identified in the axonal branches that project centrally, including their presynaptic terminals in the medial and commissural NTS. In current-clamp experiments, margatoxin (MgTx), a high-affinity blocker of Kv1.3, produced an increase in action potential duration in C-type but not A- or Ah-type neurons. To evaluate the role of Kv1.3 at the presynaptic terminal, we examined the effect of MgTx on tract evoked monosynaptic excitatory postsynaptic currents (EPSCs) in brain slices of the NTS. MgTx increased the amplitude of evoked EPSCs in a subset of neurons, with the major increase occurring during the first stimuli in a 20-Hz train. These data, together with the results from somal recordings, support the hypothesis that Kv1.3 regulates the duration of the action potential in the presynaptic terminal of C fibers, limiting transmitter release to the postsynaptic cell. PMID:21430270

  6. Fiber-optic sensor for real-time monitoring of temperature on high voltage (400KV) power transmission lines

    NASA Astrophysics Data System (ADS)

    Gangopadhyay, Tarun K.; Paul, Mukul C.; Bjerkan, Leif

    2009-10-01

    On-line monitoring of temperature and sag in 400KV power transmission line has successfully been implemented by a novel device using fibre Bragg grating (FBG) sensors. The complete device has been fabricated with aluminum mount connected via fibre-optic cable and installed on ACSR power conductor for continuous two years measurement. This paper presents the excellent results and experience of the tests in controlled indoor environments conducted in Norway and real-field application on installed power conductor in India. Thus, better surveillance of the thermal and mechanical loads on power lines can be possible using this FBG sensor system.

  7. Proposal to amend existing operating permit for the Ault-Craig 345-kV and Hayden-Archer 230-kV transmission lines, Routt, Jackson and Larimer Counties, Colorado

    SciTech Connect

    1997-08-01

    The Western Area Power Administration, Rocky Mountain Region, is proposing to amend an existing US Forest Service operating permit for the Ault-Craig 345-kV and Hayden-Archer 230-kV transmission lines, which are located in Routt, jackson, and Larimer counties, Colorado. These transmission lines cross portions of the Roosevelt and Routt National Forests. The long-term use authorization Western is requesting from the Forest Service would be for the life of the Ault-Craig and Hayden-Archer transmission lines. This environmental assessment addresses those access road and right-of-way maintenance activities identified by Western that would be performed on Forest Service managed lands during the next approximately five years.

  8. The 300-kV international submarine transmission line: Erie, Pennsylvania to Nanticoke, Ontario, Canada, General Public Utilities Corporation

    NASA Astrophysics Data System (ADS)

    1982-05-01

    This final environmental impact statement (FEIS) was prepared by the Office of Energy Emergency Operations. The proposed action by the Department of Energy is the granting of a Presidential Permit for the construction, connection, operation, and maintenance of 69.6 kilometers (44 miles) of a +250 to +325 and -250 to -325 kilovolt (250 to 325 kV) transmission facility from the Erie West Substation to the international border. The proposed project will connect the General Public Utilities Corporation System with the Ontario Hydro System for the purpose of economic exchanges of power and increased reliability. Environmental impacts expected from construction and operation of the proposed Lake Erie Interconnection appear to be mainly transitory effects on aquatic life due to construction.

  9. Seasonal Patterns of Melatonin, Cortisol, and Progesterone Secretion in Female Lambs Raised Beneath a 500-kV Transmission Line.

    SciTech Connect

    Lee, Jack M.

    1992-06-01

    Although several kinds of biological effects of electric and magnetic fields have been reported from laboratory studies, few have been independently replicated. When this study was being planned, the suppression of nighttime melatonin in rodents was thought to represent one of the strongest known effects of these fields. The effect had been replicated by a single laboratory for 60-Hz electric fields, and by multiple laboratories for d-c magnetic fields. The primary objective of this study was to determine whether the effect of electric and magnetic fields on melatonin would also occur in sheep exposed to a high voltage transmission line. The specific hypothesis tested by this experiment was as follows: The electrical environment produced by a 60-Hz, 500-kV transmission line causes a depression in nocturnal melatonin in chronically exposed female lambs. This may mimic effects of pinealectomy or constant long-day photoperiods, thus delaying the onset of reproductive cycles. Results of the study do not provide evidence to support the hypothesis. Melatonin concentrations in the sheep exposed to the transmission line showed the normal pattern of low daytime and high nighttime serum levels. As compared to the control group, there were no statistically significant group differences in the mean amplitude, phase, or duration of the nighttime melatonin elevation.

  10. Coyote Pumping Plant 115-kV transmission line project, Santa Clara County, California: Environmental assessment

    SciTech Connect

    Not Available

    1985-01-01

    Environmental impacts expected from the design and siting of transmission lines and the associated pumping plant station are addressed with alternative routes and actions considered, in compliance with environmental laws. (PSB)

  11. Supplement Analysis for the Transmission System Vegetation Management Program FEIS (DOE/EIS-0285/SA-40) - Allston-Keeler 500 kV Transmission Line

    SciTech Connect

    Hermeston, Mark W.

    2002-02-19

    Vegetation Management along the Allston-Keeler 500 kV Transmission Line ROW exclusive to BLM lands between 8/4 through 27/4. The proposed work will be accomplished in the indicated sections of the transmission line corridor with an average corridor width of 150 feet. BPA proposes to clear unwanted vegetation in the rights-of-ways and around tower structures that may impede the operation and maintenance of the subject transmission lines and access roads, including Reclaim and Danger Trees. The lands in this SA are administered by BLM. BPA plans to conduct vegetation control with the goal of removing tall growing vegetation that is currently or will soon be a hazard to the transmission line. BPA’s overall goal is to have low-growing plant communities along the rights-of-way to control the development of potentially threatening vegetation. All work will be executed in accordance with the National Electrical Safety Code and BPA standards. Work is to begin in March 2002. In accordance with a court injunction, no chemical treatment is planned on BLM lands.

  12. Seasonal Patterns of Melatonin, Cortisol, and Progesterone Secretion in Female Lambs Raised Beneath a 500-KV Transmission Line

    NASA Astrophysics Data System (ADS)

    Lee, Jack Monroe, Jr.

    There is ongoing controversy about the possibility of adverse biological effects from environmental exposures to electric and magnetic fields. These fields are produced by all electrical equipment and appliances including electrical transmission lines. The objective of this environmental science study was to investigate the possible effects of a high voltage transmission line on domestic sheep (Ovis aries L.), a species that can often be found near such lines. The study was primarily designed to determine whether a specific effect of electric and magnetic fields found in laboratory animals also occurs in livestock under natural environmental conditions. The effect is the ability of fields, at levels found in the environment, to significantly depress the normally high nocturnal concentrations of the pineal hormone-melatonin. Ten female Suffolk lambs were penned for 10 months directly beneath a 500-kV transmission line near Estacada, Oregon. Ten other lambs of the same type were penned in a control area away from the transmission line where electric and magnetic fields were at ambient levels. Serum melatonin was analyzed by radioimmunoassay (RIA) from 6618 blood samples collected at 0.5 to 3-hour intervals over eight 48-hour periods. Serum progesterone was analyzed by RIA from blood samples collected twice weekly. Serum cortisol was also assayed by RIA from the blood samples collected during the 48-hour samples. Results showed that lambs in both the control and line groups had the typical pattern of melatonin secretion consisting of low daytime and high nighttime serum concentrations. There were no statistically significant differences between groups in melatonin levels, or in the phase or duration of the nighttime melatonin elevation. Age at puberty and number of reproductive cycles also did not differ between groups. Serum cortisol showed a circadian rhythm with highest concentrations during the day. There were, however, no differences in cortisol concentrations

  13. Devils Lake main crossing of the Carrington-Devils Lake 115-kV transmission line: Environmental assessment

    SciTech Connect

    Not Available

    1985-05-01

    Planning for the proposed rebuild of the Devils Lake crossing of the Carrington-Devils Lake 115-kV Transmission Line was accomplished in consultation with a number of State and Federal agencies. Western consulted with the North Dakota State Historic Preservation Officer to identify potential significant cultural resources and effects of the project, in compliance with provisions of the National Historic Preservation Act. The FWS was consulted concerning Federally listed threatened and endangered species which the project might affect, pursuant to the Endangered Species Act. FWS and the North Dakota Department of Game and Fish were consulted regarding impacts of the project on fish, wildlife, habitat, and programs of concern to the agencies. The COE was consulted regarding the identification of wetlands in the project area, and the necessity of obtaining permits in accordance with Section 404 of the Clean Water Act and/or Section 10 of the River and Harbor Act of 1899. The US Environmental Protection Agency and North Dakota Department of Health were consulted regarding water quality impacts and the necessity of discharge permits. Prime and other important farmlands in the project area were identified by the soil Conservation Service.

  14. Environmental Assessment and Finding of No Significant Impact: Curecanti-Lost Canyon 230-kV Transmission Line Reroute Project, Montrose County, Colorado

    SciTech Connect

    N /A

    2000-03-20

    The Department of Energy (DOE), Western Area Power Administration (Western) is proposing to reroute a section of the Curecanti-Lost Canyon 230-kilovolt (kV) transmission line, in Montrose County, Colorado. A portion of the transmission line, situated 11 miles southeast of Montrose, Colorado, crosses Waterdog Peak, an area of significant geologic surface activity, which is causing the transmission line's lattice steel towers to shift. This increases stress to structure hardware and conductors, and poses a threat to the integrity of the transmission system. Western proposes to relocate the lattice steel towers and line to a more geologically stable area. The existing section of transmission line and the proposed relocation route cross Bureau of Land Management and private land holdings.

  15. Hunter survey final report, Phase I - baseline study. Garrison-Spokane 500-kV transmission project

    SciTech Connect

    Allen, S.

    1984-11-01

    The State of Montana, in cooperation with the US Forest Service and the Bonneville Power Administration, is conducting a five-year study on the impacts on elk security habitat and hunter opportunity in western Montana of a 500 kV transmission line. Potential impacts stem from the new and upgraded access roads required for the line, which may reduce summer/fall security habitat and make hunting areas less remote. The line itself could affect the aesthetics of popular hunting areas located along the route. As part of this monitoring program, the Montana Department of Natural Resources and Conservation is surveying hunters at seven check stations in the project's two study areas. The hunter survey research has three phases. Phase I was conducted in fall, 1983, to collect baseline data on hunting use and quality in the study areas. After the line is constructed and energized, the Phase II survey, scheduled for fall, 1985, will test hypotheses developed from baseline data to assess the project's impacts on hunting use. During Phase III, scheduled for fall, 1986, the persistence of any impacts identified will be measured. Reports from each phase will be issued to the Interagency Wildlife Technical Committee (chaired by the Bonneville Power Administration). The data will also be used by the Montana Department of Fish, Wildlife, and Parks, both to help manage elk and to assist in US Forest Service Land management planning. Over 600 hunters were interviewed using a questionnaire developed by DNRC and reviewed extensively by state and federal agencies. The survey form contained questions on hunters' reasons for choosing the study areas as places to hunt, hunting success and related information, previous hunting experience, hunting area evaluations, place of residence, and age. The data were tabulated to describe the 1983 baseline data, and then subjected to cluster analysis. 36 references, 1 figure, 9 tables. (ACR)

  16. 75 FR 44008 - Revised Notice of Intent To Prepare an Environmental Impact Statement for the Proposed Boardman...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-27

    ... new single-circuit 500- kilovolt (kV) electric transmission line proposed for construction by IPC... requirements in Oregon and Idaho, provide service to wholesale customers, maintain reliable electric service... application for a ROW grant to construct, operate, and maintain a single-circuit 500-kV transmission...

  17. Curecanti-Blue Mesa-Salida 115-kV transmission lines access roads rehabilitation, maintenance, and construction project. Environmental Assessment

    SciTech Connect

    Not Available

    1993-07-01

    Western Area Power Administration (Western) is a power marketing agency of the US Department of Energy, with jurisdiction in 15 western states. The Salt Lake City Area (SLCA) of Western performs the agency`s mission in parts of Colorado, New Mexico, Texas, Utah, Arizona, Wyoming, and Nevada. As part of its mission, Western owns, operates, and maintains a system of transmission lines for transmitting bulk electrical energy from points of generation to and between delivery points. Part of that system in southwestern Colorado includes the Blue Mesa-Curecanti and Blue Mesa-Salida 115-kV transmission lines. Western proposes to conduct maintenance and improve its access roads for these two transmission lines. This paper discusses the impacts to the existing environment as well as the environmental consequences resulting from the maintenance and construction that is proposed.

  18. Supplement Analysis for the Transmission System Vegetation Management Program FEIS (DOE/EIS-0285/SA-221) Project #: V-O-04/10 - Paul-Allston No 1 and 2 - 500 kV Transmission Line Corridor

    SciTech Connect

    Stratton, Elaine S.

    2004-07-26

    The project activities will be conducted along the Right-of-Way (ROW) of the Paul-Allston No 1 and 2 - 500 kV transmission line corridor between towers 45/4 and the Allston substation. This corridor includes portions of the Longview-Allston No 1 and 2 and the Longview-Allston No 3 and 4 - 230 kV transmission lines. The corridor along this section of the proposed project varies between 125 and 150 feet in width and crosses approximately 4 miles of terrain from Longview, Washington crossing the Columbia River and passing through rural forestland and pasture lands to the Allston Substation in Oregon. BPA proposes to remove unwanted vegetation along the right-of-way, along access roads and around tower structures along the subject transmission line corridor that may impede the operation and maintenance of the identified transmission lines. BPA plans to conduct vegetation control with the goal of removing tall growing vegetation that is currently or will soon be a hazard to the transmission line. BPA’s overall goal is to have low-growing plant communities along the rights-of-way to control the development of potentially threatening vegetation.

  19. Environmental Assessment for Central Power and Light Company`s proposed Military Highway-CFE tie 138/69-kV transmission line project Brownsville, Cameron County, Texas

    SciTech Connect

    Not Available

    1992-04-01

    Central Power and Light Company (CPL) intends to upgrade its existing transmission line ties with the Commision Federal de Electricidad (CFE) system in Mexico. CPL currently has a single 69-kilovolt (kV) transmission line in the Brownsville area which connects CPL`s system with the system of CFE. This existing line runs between the Brownsville Switching Station, located on Laredo Road in Brownsville, Cameron County, Texas, and an existing CFE 69-kV line at the Rusteberg Bend of the Rio Grande in Cameron County. Under current conditions of need, the existing 69-kV line does not possess sufficient capability to engage in appropriate power exchanges. Therefore, CPL is proposing to build a new line to link up with CFE. This proposed line would be a double-circuit line, which would (1) continue (on a slightly relocated route) the existing 69-kV tie from CPL`s Brownsville Switching Station to CFE`s facilities, and (2) add a 138-kV tie from the Military Highway Substation, located on Military Highway (US Highway 281), to CFE`s facilities. The proposed 138/69-kV line, which will be constructed and operated by CPL, will be built primarily on steel single-pole structures within an average 60-foot (ft) wide right-of-way (ROW). It will be approximately 6900--9200 ft (1.3--1.7 miles) in length, depending on the alternative route constructed.

  20. 75 FR 3486 - Susquehanna to Roseland 500kV Transmission Line, Environmental Impact Statement, Delaware Water...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-21

    ... Pennsylvania Power and Light Electric Utilities (PPL) and Public Service Electric and Gas Company (PSE&G), and... expand the width of the transmission line right-of-way beyond the Applicant's current holdings. The... need to expand its current right-of-way to construct new and taller power lines and add an...

  1. 30-kV spin-polarized transmission electron microscope with GaAs-GaAsP strained superlattice photocathode

    NASA Astrophysics Data System (ADS)

    Kuwahara, M.; Kusunoki, S.; Jin, X. G.; Nakanishi, T.; Takeda, Y.; Saitoh, K.; Ujihara, T.; Asano, H.; Tanaka, N.

    2012-07-01

    A spin-polarized electron beam has been used as the probe beam in a transmission electron microscope by using a photocathode electron gun with a photocathode made of a GaAs-GaAsP strained superlattice semiconductor with a negative electron affinity (NEA) surface. This system had a spatial resolution of the order of 1 nm for at 30 keV and it can generate an electron beam with an energy width of 0.24 eV without employing monochromators. This narrow width suggests that a NEA photocathode can realize a high energy resolution in electron energy-loss spectroscopy and a longitudinal coherence of 3 × 10-7 m.

  2. Proposed amendment for Presidential Permit PP-63 and associated modifications to 500 kV international transmission line, Forbes, Minnesota to Manitoba, Canada Northern States Power Company. Final Environmental Assessment

    SciTech Connect

    Not Available

    1992-02-01

    Northern States Power Company, (NSP), a Minnesota investor owned utility has applied to the Office of Fossil Energy, United States Department of Energy, to amend Presidential Permit PP-63 to allow for alterations to the 500 kV transmission line and as sedated facilities currently regulated by this permit. The alterations proposed for the 500 kV line owned by NSP are part of a long term effort sponsored by NSP to upgrade the existing NSP transmission system to allow for increased exchange of electricity with the Manitoba Hydro-Electric Board. Presidential Permit PP-63 authorized NSP to construct, connect, operate and maintain a 500 kV line at the United States/Canadian border approximately seven-and-a-half miles west of Warroad in Roseau County, Minnesota. This line connects with a 500 kV line owned and operated by the Manitoba Hydro-Electric Board (MHEB), which extends from Dorsey, Manitoba, Canada to the United States/Canadian border. NSP proposes to increase the electricity transfer capability of this transmission facility by constructing a new 80-acre substation on the existing 500 kV line in Roseau County, Minnesota, and upgrading the existing substation at Forbes, Minnesota. The proposed Roseau substation would contain two 41.5 ohm series capacitor banks. In addition, static VAR compensators are to be installed at the existing Forbes Substation. Approximately 5 acres would be added to the 30-acre Forbes site to house the additional equipment. No new lines would enter or exit the facility. NSP proposes to place the new Roseau Substation in service in May 1993 and to complete the upgrading of the Forbes Substation in March 1994. The primary, initial purpose of these modifications is to enable NSP to import 400 megawatts of electric power from MHEB during the summer months to meet peak electrical demand in the Minneapolis-St. Paul area. It is expected that this power transfer would begin in 1993.

  3. 77 FR 10502 - Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-22

    ... Franklin D. Roosevelt Lake (Roosevelt Lake), near the town of Grand Coulee, Douglas and Grant Counties... racks; (2) a 1.5-mile-long penstock consisting of a vertical shaft, power tunnel segments, and a...; (4) a 2-mile-long, 500-kilovolt (kV) transmission line extending from the project powerhouse to...

  4. 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

  5. Environmental Assessment and Finding of No Significant Impact: Western's Hoover Dam Bypass Project Phase II (Double-Circuiting a Portion of the Hoover-Mead No.5 and No.7 230-kV Transmission Lines with the Henderson-Mead No.1 230-kV Transmission Line, Clark County, Nevada)

    SciTech Connect

    N /A

    2003-10-27

    The U.S. Highway 93 (U.S. 93) Hoover Dam Bypass Project calls for the U.S. Department of Energy (DOE) Western Area Power Administration (Western) to remove its Arizona and Nevada (A&N) Switchyard. As a result of this action, Western must reconfigure its existing electrical transmission system in the Hoover Dam area. Western proposes to double-circuit a portion of the Hoover-Mead No.5 and No.7 230-kV Transmission Lines with the Henderson-Mead No.1 Transmission Line (see Figure 1-1). Double-circuiting is the placement of two separate electrical circuits, typically in the form of three separate conductors or bundles of conductors, on the same set of transmission line structures. The old Henderson-Hoover 230-kV Transmission Line would become the new Henderson-Mead No.1 and would extend approximately eight miles to connect with the Mead Substation. Western owns, operates, and maintains the Hoover-Mead No.5 and No.7, and Henderson-Hoover electrical power transmission lines. Additionally, approximately 0.25 miles of new right-of-way (ROW) would be needed for the Henderson-Mead No.1 when it transfers from double-circuiting with the Hoover-Mead No.7 to the Hoover-Mead No.5 at the Boulder City Tap. The proposed project would also involve a new transmission line ROW and structures where the Henderson-Mead No.1 will split from the Hoover-Mead No.5 and enter the northeast corner of the Mead Substation. Lastly, Western has proposed adding fiber optic overhead ground wire from the Hoover Power Plant to the Mead Substation on to the Henderson-Mead No.1, Hoover-Mead No.5 and No.7 Transmission Lines. The proposed project includes replacing existing transmission line tower structures, installing new structures, and adding new electrical conductors and fiber optic cables. As a consequence of these activities, ground disturbance may result from grading areas for structure placement, constructing new roads, improving existing roads for vehicle and equipment access, and from installing

  6. Neuroprotective or neurotoxic effects of 4-aminopyridine mediated by KChIP1 regulation through adjustment of Kv 4.3 potassium channels expression and GABA-mediated transmission in primary hippocampal cells.

    PubMed

    Del Pino, Javier; Frejo, María Teresa; Baselga, María José Anadon; Capo, Miguel Andrés; Moyano, Paula; García, José Manuel; Díaz, María Jesús

    2015-07-01

    4-Aminopyridine (4-AP) is a potassium channel blocker used for the treatment of neuromuscular disorders. Otherwise, it has been described to produce a large number of adverse effects among them cell death mediated mainly by blockage of K(+) channels. However, a protective effect against cell death has also been described. On the other hand, Kv channel interacting protein 1 (KChIP1) is a neuronal calcium sensor protein that is predominantly expressed at GABAergic synapses and it has been related with modulation of K(+) channels, GABAergic transmission and cell death. According to this KChIP1 could play a key role in the protective or toxic effects induced by 4-AP. We evaluated, in wild type and KChIP1 silenced primary hippocampal neurons, the effect of 4-AP (0.25μM to 2mM) with or without semicarbazide (0.3M) co-treatment after 24h and after 14 days 4-AP alone exposure on cell viability, the effect of 4-AP (0.25μM to 2mM) on KChIP1 and Kv 4.3 potassium channels gene expression and GABAergic transmission after 24h treatment or after 14 days exposure to 4-AP (0.25μM to1μM). 4-AP induced cell death after 24h (from 1mM) and after 14 days treatment. We observed that 4-AP modulates KChIP1 which regulate Kv 4.3 channels expression and GABAergic transmission. Our study suggests that KChIP1 is a key gene that has a protective effect up to certain concentration after short-term treatment with 4-AP against induced cell injury; but this protection is erased after long term exposure, due to KChIP1 down-regulation predisposing cell to 4-AP induced damages. These data might help to explain protective and toxic effects observed after overdose and long term exposure.

  7. Proposed Amendment to Presidential Permit PP-63 and Associated Modifications to 500-kV International Transmission Line: Forbes, Minnesota to Manitoba, Canada, Northern States Power Company. Addendum to the final Environmental Assessment

    SciTech Connect

    Not Available

    1992-10-01

    This Addendum to the Final Environmental Assessment for the Proposed Amendment to Presidential Permit PP-63 and Associated Modifications to 500 kV International Transmission Line: Forbes, Minnesota to Manitoba, Canada (DOE/EA-587) addresses Northern States Power Company`s (NSP) proposed expansion of the Forbes Substation. The applicant has requested that the expansion take place on the west side of the substation, within the existing property line, instead of on the north side as originally proposed. All of the proposed construction would take place on property already owned by NSP. DOE has reviewed the environmental impacts associated with this minor modification and has determined that the conclusions reached in the environmental assessment and Finding of No Significant Impact prepared in connection with NSP`s original amendment request remain valid.

  8. Draft environmental impact statement for construction and operation of the proposed Bangor Hydro-Electric Company`s second 345-kV transmission tie line to New Brunswick

    SciTech Connect

    1993-10-01

    This Draft Environmental Impact Statement (DEIS) was prepared by the US Department of Energy (US DOE). The proposed action is the issuance of Presidential Permit PP-89 by DOE to Bangor Hydro-Electric Company to construct and operate a new international transmission line interconnection to New Brunswick, Canada that would consist of an 83.8 mile (US portion), 345-kilovolt (kV) alternating current transmission line from the US-Canadian border at Baileyville, Maine to an existing substation at Orrington, Maine. The principal environmental impacts of the construction and operation of the transmission line would be incremental in nature and would include the conversion of forested uplands (mostly commercial timberlands) and wetlands to right-of-way (small trees, shrubs, and herbaceous vegetation). The proposed line would also result in localized minor to moderate visual impacts and would contribute a minor incremental increase in the exposure of some individuals to electromagnetic fields. This DEIS documents the purpose and need for the proposed action, describes the proposed action and alternatives considered and provides a comparison of the proposed and alternatives routes, and provides detailed information on analyses of the environmental consequences of the proposed action and alternatives, as well as mitigative measures to minimize impacts.

  9. Impact Mitigation and Monitoring of the BPA 500-kV Garrison-Taft Transmission Line : Effects on Elk Security and Hunter Opportunity, Final Report.

    SciTech Connect

    Canfield, Jodie E.

    1988-11-01

    This study was conducted by the Montana Department of Fish, Wildlife and Parks from 1984--1988 to assess the impacts of the Garrison-Taft segment of a 500-kV powerline on elk summer-fall habitat. Construction of the powerline began in 1983, and the powerline was energized in 1985. The Garrison-Taft powerline corridor crossed 251 km of mountainous terrain in western Montana; about 465 km of new roads were constructed to provide permanent access to the powerline towers. The objectives of the study were: (1) to monitor the effectiveness of mitigation measures, including timing restrictions on construction activities and road closures on newly-built access roads, and (2) to determine if opening previously-unroaded elk security habitats to hunters by powerline access roads affected elk habitat use, distribution, use of security areas, or elk harvest. In addition, both the potential for accelerated timber harvest in areas crossed by the powerline that would not have otherwise been logged because of marginal economics and lack of haul roads and the potential effect of powerline flashovers on future prescribed burning of elk winter-ranges were evaluated. 83 refs., 88 figs., 15 tabs.

  10. El Paso Electric Company Diablo Substation to the US-Mexico border 115kV transmission line project. Final Environmental Assessment

    SciTech Connect

    Not Available

    1992-04-01

    This Environmental Assessment documents the analysis of alternative corridors for development and operation of a proposed 115 kilovolt transmission line using private lands and transporting power to the US-Mexico international border. The project will require (1) an amendment to El Paso Electric Company`s existing export authorization to transfer power across this border, and (2) a Presidential Permit for construction of the transmission line. The project would be located in Dona Ana county in southern New Mexico, approximately five miles west of El Paso, Texas. The alternative corridors, specific locations within those corridors, and structure types are identified and analyzed in the environmental studies.

  11. Impact Mitigation and Monitoring of the BPA 500 KV Garrison-Taft Transmission Line : Effects on Elk Security and Hunter Opportunity : Annual Progress Report for 1986.

    SciTech Connect

    Thompson, Michael J.; Dickson, David C.

    1987-06-01

    The objectives were: (1) to determine the effectiveness of the mitigation measures employed in the Garrison-Taft Project to minimize impacts on elk; (2) to determine the nature and magnitude of the Project impacts on elk summer-fall habitat use, distribution, use of security areas, and harvest, with emphasis on the adult male segment of the population; (3) to identify and recommend protection for important elk security areas remaining in areas adjacent to the Project; (4) to assess Project impacts on hunter opportunity and on hunters' perceptions of hunting as related to the transmission line, right-of-way, and road systems; (5) to reduce to the extent possible the net Project impacts on elk and elk hunter opportunity; and (6) to determine appropriate measures for offsetting unmitigated impacts. This involved assessing Project-caused changes along the entire route and comparing these with documented impacts on elk and elk hunting within the study areas.

  12. Overview of MoronytoRainbow Line (background) in context with RyantoRainbow 100kV ...

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

    Overview of Morony-to-Rainbow Line (background) in context with Ryan-to-Rainbow 100kV Transmission Lines 1 and 2 (center and foreground) about three miles southwest of Morony Dam and Powerhouse. View to north - Morony Hydroelectric Facility, Morony-to-Rainbow 100 kV Transmission Line, West bank of the Missouri River, Great Falls, Cascade County, MT

  13. Kv1.5 Association Modifies Kv1.3 Traffic and Membrane Localization*S⃞

    PubMed Central

    Vicente, Rubén; Villalonga, Núria; Calvo, Maria; Escalada, Artur; Solsona, Carles; Soler, Concepció; Tamkun, Michael M.; Felipe, Antonio

    2008-01-01

    Kv1.3 activity is determined by raft association. In addition to Kv1.3, leukocytes also express Kv1.5, and both channels control physiological responses. Because the oligomeric composition may modify the channel targeting to the membrane, we investigated heterotetrameric Kv1.3/Kv1.5 channel traffic and targeting in HEK cells. Kv1.3 and Kv1.5 generate multiple heterotetramers with differential surface expression according to the subunit composition. FRET analysis and pharmacology confirm the presence of functional hybrid channels. Raft association was evaluated by cholesterol depletion, caveolae colocalization, and lateral diffusion at the cell surface. Immunoprecipitation showed that both Kv1.3 and heteromeric channels associate with caveolar raft domains. However, homomeric Kv1.3 channels showed higher association with caveolin traffic. Moreover, FRAP analysis revealed higher mobility for hybrid Kv1.3/Kv1.5 than Kv1.3 homotetramers, suggesting that heteromers target to distinct surface microdomains. Studies with lipopolysaccharide-activated macrophages further supported that different physiological mechanisms govern Kv1.3 and Kv1.5 targeting to rafts. Our results implicate the traffic and localization of Kv1.3/Kv1.5 heteromers in the complex regulation of immune system cells. PMID:18218624

  14. 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.

  15. China's transmission mushrooms

    SciTech Connect

    Defang, C.

    1980-08-01

    Thirty years ago, when the People's Republic of China was founded, there were only three high-voltage transmission grids in the entire country, totaling only 500 km (311 mi.) in length. Today, there are 13 distinct major regional networks, plus a number of smaller ones, with a cumulative length of 230,000 km (142,900 mi) and operating at voltages up to 330 kV. Those transmission lines that did exist in 1949 operated at only 35 kV, with the single exception of one regional grid of 220 kV in northeastern China. Even for those modest voltages, essentially all transmission and distribution equipment had to be imported.

  16. 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

  17. Auxiliary KCNE subunits modulate both homotetrameric Kv2.1 and heterotetrameric Kv2.1/Kv6.4 channels

    PubMed Central

    David, Jens-Peter; Stas, Jeroen I.; Schmitt, Nicole; Bocksteins, Elke

    2015-01-01

    The diversity of the voltage-gated K+ (Kv) channel subfamily Kv2 is increased by interactions with auxiliary β-subunits and by assembly with members of the modulatory so-called silent Kv subfamilies (Kv5-Kv6 and Kv8-Kv9). However, it has not yet been investigated whether these two types of modulating subunits can associate within and modify a single channel complex simultaneously. Here, we demonstrate that the transmembrane β-subunit KCNE5 modifies the Kv2.1/Kv6.4 current extensively, whereas KCNE2 and KCNE4 only exert minor effects. Co-expression of KCNE5 with Kv2.1 and Kv6.4 did not alter the Kv2.1/Kv6.4 current density but modulated the biophysical properties significantly; KCNE5 accelerated the activation, slowed the deactivation and steepened the slope of the voltage-dependence of the Kv2.1/Kv6.4 inactivation by accelerating recovery of the closed-state inactivation. In contrast, KCNE5 reduced the current density ~2-fold without affecting the biophysical properties of Kv2.1 homotetramers. Co-localization of Kv2.1, Kv6.4 and KCNE5 was demonstrated with immunocytochemistry and formation of Kv2.1/Kv6.4/KCNE5 and Kv2.1/KCNE5 complexes was confirmed by Fluorescence Resonance Energy Transfer experiments performed in HEK293 cells. These results suggest that a triple complex consisting of Kv2.1, Kv6.4 and KCNE5 subunits can be formed. In vivo, formation of such tripartite Kv2.1/Kv6.4/KCNE5 channel complexes might contribute to tissue-specific fine-tuning of excitability. PMID:26242757

  18. Kv1 channels and neural processing in vestibular calyx afferents.

    PubMed

    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

  19. 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

  20. Mitochondrial Ultrastructure and Glucose Signaling Pathways Attributed to the Kv1.3 Ion Channel.

    PubMed

    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 interested to

  1. TVA's 500-kV electric and magnetic fields: measurements and analyses

    SciTech Connect

    Not Available

    1983-09-01

    This report summarizes the results of the 500-kV electric and magnetic fields data project, performed by the Electrical Systems Group of the Tennessee Valley Authority (TVA). The objectives of the project were to measure, record, and analyze electric and magnetic fields in the vicintiy of TVA's 500-kV transmission lines. Also the effects of transmission line fields on the growth and development of selected agricultural and forest plant species were to be investigated. This report contains only the categorization and the statistical analysis of the fields data.

  2. Supplement Analysis for the Transmission System Vegetation Management Program FEIS (DOE/EIS-0285/SA-130- Keeler-Tillamook)

    SciTech Connect

    Sherer, Brett M.

    2003-03-10

    Vegetation Management for the Keeler Tillamook 115 kV transmission line from structure 1/7 through structure 58/2, and along adjacent portions of the Keeler-Forest Grove #2 115KV transmission line. In addition the project includes 11miles of the 115KV Timber Tap.

  3. 76 FR 41791 - Environmental Impacts Statements; Notice of Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-15

    ..., Final EIS, BPA, 00, Big Eddy-Knight Transmission Project, Proposal to Construct, Operate, and Maintain a 27-28 mile long 500-Kilovolt Transmission Line using a Combination of Existing BPA and New...

  4. 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

  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. 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

  7. Development of Y-branch Joint for 275kV XLPE and Fluid Filled Cable

    NASA Astrophysics Data System (ADS)

    Goto, Takeshi; Yamashita, Makoto; Sakamaki, Masatoshi

    When a new UHV substation is built in an urban region, generally, an existing underground transmission line shall be diverted and drawn into the new substation. Compared with above mentioned construction method, enormous cost reduction of switching facilities and cable construction is expected with applying a Y-Branch Joint (YJ) which is able to be a 3-way joint. The YJ has already been applied for 154kV class circuit, however, it has not been investigated for 275kV class circuit. Since both XLPE and Fluid-Filled cable are presently used in 275kV class underground cable line, an universal design YJ for both cables have been investigated. The YJ was applied a compact design which was based on our sophisticated electrical stress control technology for 500kV prefabricated type joint. Furthermore, the design was based on its prefabricated assembling technology. The YJ was verified its electrical and mechanical performance as 275kV cable joint by completion of its assembling test and a long term electrical test.

  8. New inhibitors of the Kvβ2 subunit from mammalian Kv1 potassium channels.

    PubMed

    Alka, Kumari; Dolly, J Oliver; Ryan, Barry J; Henehan, Gary T M

    2014-10-01

    The role of the redox state of Kvβ subunits in the modulation of Kv1 potassium channels has been well documented over the past few years. It has been suggested that a molecule that binds to or inhibits the aldo-keto reductase activity of Kvβ might affect the modulation of channel properties. Previous studies of possible modulators of channel activity have shown that cortisone and some related compounds are able to physically dissociate the channel components by binding to a site at the interface between α and β subunits. Herein, we describe some new inhibitors of rat brain Kvβ2, identified using an assay based on multiple substrate turnover. This approach allows one to focus on molecules that specifically block NADPH oxidation. These studies showed that, at 0.5mM, 3,4-dihydroxphenylacetic acid (DOPAC) was an inhibitor of Kvβ2 turnover yielding a ∼ 40-50% reduction in the aldehyde reductase activity of this subunit. Other significant inhibitors include the bioflavinoid, rutin and the polyphenol resveratrol; some of the known cardioprotective effects of these molecules may be attributable to Kv1 channel modulation. Cortisone or catechol caused moderate inhibition of Kvβ2 turnover, and the aldo-keto reductases inhibitor valproate had an even smaller effect. Despite the importance of the Kv1 channels in a number of disease states, there have been few Kvβ2 inhibitors reported. While the ones identified in this study are only effective at high concentrations, they could serve as tools to decipher the role of Kvβ2 in vivo and, eventually, inform the development of novel therapeutics.

  9. Optimum HRTEM image contrast at 20 kV and 80 kV--exemplified by graphene.

    PubMed

    Lee, Z; Meyer, J C; Rose, H; Kaiser, U

    2012-01-01

    The dependence of high-resolution transmission electron microscopy (HRTEM) image contrast of graphene on the adjustable parameters of an aberration-corrected microscope operated at 80 and 20 kV has been calculated and, for 80 kV, compared with measurements. We used density functional theory to determine the projected atom potential and obtained the image intensity by averaging over the energy distribution of the imaging electrons, as derived from the electron energy loss spectroscopy measurements. Optimum image contrast has been determined as a function of energy spread of the imaging electrons and chromatic aberration coefficient, showing that significant improvement of contrast can be achieved at 80 kV with the help of a monochromator, however at 20 kV only with chromatic aberration correction and bright atom contrast conditions.

  10. Problems of operating the 500-kV outdoor electrical equipment of the Sayano-Shushenskoe hydroelectric station

    SciTech Connect

    Mitrofanov, A.N.

    1994-10-01

    The Sayano-Shushenskoe hydroelectric station is part of the Siberian interconnected power system. Power is transmitted to the grid by two 500 kV transmission lines. The site characteristics made nearby placement of conventional 500 kV switchyard equipment impossible. The original plans were to place the switchyard 35 km away, but the 500 kV lines to the yard would have passed through mountain regions with intense thunderstorm activity. Because of the unique design of the generators, the number of lightning-induced disconnects was substantial. For greater reliability, 500 kV equipment suitable for placement at the sight was designed, and the overall electrical layout of the yard was revised by reconstructing the middle network of the 4/3 scheme to three networks with two switches per connection. Sectioning of the collecting bus systems was necessary for a further increase in the reliability of the yard.

  11. Concatemers of brain Kv1 channel alpha subunits that give similar K+ currents yield pharmacologically distinguishable heteromers.

    PubMed

    Sokolov, Maxim V; Shamotienko, Oleg; Dhochartaigh, Sorcha Ní; Sack, Jon T; Dolly, J Oliver

    2007-08-01

    At least five subtypes of voltage-gated (Kv1) channels occur in neurons as tetrameric combinations of different alpha subunits. Their involvement in controlling cell excitability and synaptic transmission make them potential targets for neurotherapeutics. As a prerequisite for this, we established herein how the characteristics of hetero-oligomeric K(+) channels can be influenced by alpha subunit composition. Since the three most prevalent Kv1 subunits in brain are Kv1.2, 1.1 and 1.6, new Kv1.6-1.2 and Kv1.1-1.2 concatenated constructs in pIRES-EGFP were stably expressed in HEK cells and the biophysical plus pharmacological properties of their K(+) currents determined relative to those for the requisite homo-tetramers. These heteromers yielded delayed-rectifier type K(+) currents whose activation, deactivation and inactivation parameters are fairly similar although substituting Kv1.1 with Kv1.6 led to a small negative shift in the conductance-voltage relationship, a direction unexpected from the characteristics of the parental homo-tetramers. Changes resulting from swapping Kv1.6 for Kv1.1 in the concatemers were clearly discerned with two pharmacological agents, as measured by inhibition of the K(+) currents and Rb(+) efflux. alphaDendrotoxin and 4-aminopyridine gave a similar blockade of both hetero-tetramers, as expected. Most important for pharmacological dissection of channel subtypes, dendrotoxin(k) and tetraethylammonium readily distinguished the susceptible Kv1.1-1.2 containing oligomers from the resistant Kv1.6-1.2 channels. Moreover, the discriminating ability of dendrotoxin(k) was further confirmed by its far greater ability to displace (125)I-labelled alphadendrotoxin binding to Kv1.1-1.2 than Kv1.6-1.2 channels. Thus, due to the profiles of these two channel subtypes being found to differ, it seems that only multimers corresponding to those present in the nervous system provide meaningful targets for drug development.

  12. 77 FR 514 - Notice of Availability of the Record of Decision for the North Steens 230 Kilovolt Transmission...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-05

    ..., maintenance and termination of a 230-kV transmission line, tensioning sites and related access across lands... Kilovolt Transmission Line, Harney County, OR AGENCY: Bureau of Land Management, Interior. ACTION: Notice... Record of Decision (ROD) for the North Steens 230 kilovolt (kV) Transmission Line Project. The...

  13. 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.

  14. 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

  15. 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. PMID:27379187

  16. Supplement Analysis for the Transmission System Vegetation Management Program FEIS (DOE/EIS-0285/SA-222)

    SciTech Connect

    Stratton, Elaine S.

    2004-07-27

    Vegetation Management along the St. John’s - Keeler 115 kV Transmission Line Corridor from 3/1 to 10/6. This corridor includes portions of the Oregon City - Keeler No 2 115 kV transmission line. The corridor along this section of the proposed project is 100 feet in width.

  17. Development of 66kV XLPE submarine cable using optical fiber as a mechanical-damage-detection-sensor

    SciTech Connect

    Nishimoto, Toshio; Miyahara, Tsutomu; Takehana, Hajime; Tateno, Fuminori

    1995-10-01

    Submarine cables are exposed to great risk of serious mechanical damage by ship anchors or equipment used for fishing. Detection of such damage in a submarine cable is a very useful technology for improving the reliability of a submarine cable transmission line. A mechanical-damage-detection-sensor using optical fiber was developed. A prototype 66kV XLPE submarine cable incorporating the sensor was manufactured for trial, and the ability of a sensor was confirmed by compression test. Actual 66kV XLPE submarine cable incorporating the sensor was manufactured for trial, and the ability of a sensor was confirmed by compression test. Actual 66kV XLPE submarine cable with the sensor was manufactured and installed as an operating transmission line in Japan.

  18. Materials science applications of a 120 kV FEG TEM/STEM: Triskaidekaphilia

    SciTech Connect

    Bentley, J.; Fisher, A.T.; Kenik, E.A.; Wang, Z.L.

    1991-01-01

    The introduction by several manufacturers of 200kV transmission electron microscopes (TEM) equipped with field emission guns affords the opportunity to assess their potential impact on materials science by examining applications of similar 100-120kV instruments that have been in use for more than a decade. This summary is based on results from a Philips EM400T/FEG configured as an analytical electron microscope (AEM) with a 6,585 scanning transmission (STEM) unit, EDAX 9100/70 or 9900 energy dispersive X-ray spectroscopy (EDS) systems, and Gatan 607 serial- or 666 parallel-detection electron energy-loss spectrometers (EELS). Examples in four areas that illustrate applications that are impossible or so difficult as to be impracticable with conventional thermionic electron guns are described.

  19. Mutation of histidine 105 in the T1 domain of the potassium channel Kv2.1 disrupts heteromerization with Kv6.3 and Kv6.4.

    PubMed

    Mederos Y Schnitzler, Michael; Rinné, Susanne; Skrobek, Lennart; Renigunta, Vijay; Schlichthörl, Günter; Derst, Christian; Gudermann, Thomas; Daut, Jürgen; Preisig-Müller, Regina

    2009-02-13

    The voltage-activated K(+) channel subunit Kv2.1 can form heterotetramers with members of the Kv6 subfamily, generating channels with biophysical properties different from homomeric Kv2.1 channels. The N-terminal tetramerization domain (T1) has been shown previously to play a role in Kv channel assembly, but the mechanisms controlling specific heteromeric assembly are still unclear. In Kv6.x channels the histidine residue of the zinc ion-coordinating C3H1 motif of Kv2.1 is replaced by arginine or valine. Using a yeast two-hybrid assay, we found that substitution of the corresponding histidine 105 in Kv2.1 by valine (H105V) or arginine (H105R) disrupted the interaction of the T1 domain of Kv2.1 with the T1 domains of both Kv6.3 and Kv6.4, whereas interaction of the T1 domain of Kv2.1 with itself was unaffected by this mutation. Using fluorescence resonance energy transfer (FRET), interaction could be detected between the subunits Kv2.1/Kv2.1, Kv2.1/Kv6.3, and Kv2.1/Kv6.4. Reduced FRET signals were obtained after co-expression of Kv2.1(H105V) or Kv2.1(H105R) with Kv6.3 or Kv6.4. Wild-type Kv2.1 but not Kv2.1(H105V) could be co-immunoprecipitated with Kv6.4. Co-expression of dominant-negative mutants of Kv6.3 reduced the current produced Kv2.1, but not of Kv2.1(H105R) mutants. Co-expression of Kv6.3 or Kv6.4 with wt Kv2.1 but not with Kv2.1(H105V) or Kv2.1(H105R) changed the voltage dependence of activation of the channels. Our results suggest that His-105 in the T1 domain of Kv2.1 is required for functional heteromerization with members of the Kv6 subfamily. We conclude from our findings that Kv2.1 and Kv6.x subunits have complementary T1 domains that control selective heteromerization. PMID:19074135

  20. Environmental studies for a 1100-kV power line in Oregon. A special report

    SciTech Connect

    Rogers, L.; Hinds, R.

    1983-01-01

    In the first research project to monitor the effects of 1100-kV transmission on a natural ecosystem, researchers at Battelle, Pacific Northwest Laboratories have studied responses of wildlife, native plants, honeybees, and agricultural crops and cattle. No adverse effects were detected on wildlife, crops or cattle. Effects were observed on trees growing within the defined right of way and on honeybee colonies placed beneath the line.

  1. Record of Decision for the Electrical Interconnection of the Windy Point Wind Energy Project.

    SciTech Connect

    United States. Bonneville Power Administration.

    2006-11-01

    The Bonneville Power Administration (BPA) has decided to offer contract terms for interconnection of 250 megawatts (MW) of power to be generated by the proposed Windy Point Wind Energy Project (Wind Project) into the Federal Columbia River Transmission System (FCRTS). Windy Point Partners, LLC (WPP) propose to construct and operate the proposed Wind Project and has requested interconnection to the FCRTS. The Wind Project will be interconnected at BPA's Rock Creek Substation, which is under construction in Klickitat County, Washington. The Rock Creek Substation will provide transmission access for the Wind Project to BPA's Wautoma-John Day No.1 500-kilovolt (kV) transmission line. BPA's decision to offer terms to interconnect the Wind Project is consistent with BPA's Business Plan Final Environmental Impact Statement (BP EIS) (DOE/EIS-0183, June 1995), and the Business Plan Record of Decision (BP ROD, August 15, 1995). This decision thus is tiered to the BP ROD.

  2. 76 FR 56791 - Notice of Availability of Record of Decision for the Tropic To Hatch (Garkane) 138 kV...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-14

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF THE INTERIOR Bureau of Land Management Notice of Availability of Record of Decision for the Tropic To Hatch (Garkane... (ROD) for the Tropic to Hatch (Garkane) 138 kilovolt (kV) Transmission Line Environmental...

  3. The Subfamily-Specific Interaction between Kv2.1 and Kv6.4 Subunits Is Determined by Interactions between the N- and C-termini

    PubMed Central

    Bocksteins, Elke; Mayeur, Evy; Van Tilborg, Abbi; Regnier, Glenn; Timmermans, Jean-Pierre; Snyders, Dirk J.

    2014-01-01

    The “silent” voltage-gated potassium (KvS) channel subunit Kv6.4 does not form electrically functional homotetramers at the plasma membrane but assembles with Kv2.1 subunits, generating functional Kv2.1/Kv6.4 heterotetramers. The N-terminal T1 domain determines the subfamily-specific assembly of Kv1-4 subunits by preventing interactions between subunits that belong to different subfamilies. For Kv6.4, yeast-two-hybrid experiments showed an interaction of the Kv6.4 N-terminus with the Kv2.1 N-terminus, but unexpectedly also with the Kv3.1 N-terminus. We confirmed this interaction by Fluorescence Resonance Energy Transfer (FRET) and co-immunoprecipitation (co-IP) using N-terminal Kv3.1 and Kv6.4 fragments. However, full-length Kv3.1 and Kv6.4 subunits do not form heterotetramers at the plasma membrane. Therefore, additional interactions between the Kv6.4 and Kv2.1 subunits should be important in the Kv2.1/Kv6.4 subfamily-specificity. Using FRET and co-IP approaches with N- and C-terminal fragments we observed that the Kv6.4 C-terminus physically interacts with the Kv2.1 N-terminus but not with the Kv3.1 N-terminus. The N-terminal amino acid sequence CDD which is conserved between Kv2 and KvS subunits appeared to be a key determinant since charge reversals with arginine substitutions abolished the interaction between the N-terminus of Kv2.1 and the C-terminus of both Kv2.1 and Kv6.4. In addition, the Kv6.4(CKv3.1) chimera in which the C-terminus of Kv6.4 was replaced by the corresponding domain of Kv3.1, disrupted the assembly with Kv2.1. These results indicate that the subfamily-specific Kv2.1/Kv6.4 heterotetramerization is determined by interactions between Kv2.1 and Kv6.4 that involve both the N- and C-termini in which the conserved N-terminal CDD sequence plays a key role. PMID:24901643

  4. Fe2O3 nanoparticles suppress Kv1.3 channels via affecting the redox activity of Kvβ2 subunit in Jurkat T cells

    NASA Astrophysics Data System (ADS)

    Yan, Li; Liu, Xiao; Liu, Wei-Xia; Tan, Xiao-Qiu; Xiong, Fei; Gu, Ning; Hao, Wei; Gao, Xue; Cao, Ji-Min

    2015-12-01

    Superparamagnetic iron oxide nanoparticles (SPIONs) are promising nanomaterials in medical practice due to their special magnetic characteristics and nanoscale size. However, their potential impacts on immune cells are not well documented. This study aims to investigate the effects of Fe2O3 nanoparticles (Fe2O3-NPs) on the electrophysiology of Kv1.3 channels in Jurkat T cells. Using the whole-cell patch-clamp technique, we demonstrate that incubation of Jurkat cells with Fe2O3-NPs dose- and time-dependently decreased the current density and shifted the steady-state inactivation curve and the recovery curve of Kv1.3 channels to a rightward direction. Fe2O3-NPs increased the NADP level but decreased the NADPH level of Jurkat cells. Direct induction of NADPH into the cytosole of Jurkat cells via the pipette abolished the rightward shift of the inactivation curve. In addition, transmission electron microscopy showed that Fe2O3-NPs could be endocytosed by Jurkat cells with relatively low speed and capacity. Fe2O3-NPs did not significantly affect the viability of Jurkat cells, but suppressed the expressions of certain cytokines (TNFα, IFNγ and IL-2) and interferon responsive genes (IRF-1 and PIM-1), and the time courses of Fe2O3-NPs endocytosis and effects on the expressions of cytokines and interferon responsive genes were compatible. We conclude that Fe2O3-NPs can be endocytosed by Jurkat cells and act intracellularly. Fe2O3-NPs decrease the current density and delay the inactivation and recovery kinetics of Kv1.3 channels in Jurkat cells by oxidizing NADPH and therefore disrupting the redox activity of the Kvβ2 auxiliary subunit, and as a result, lead to changes of the Kv1.3 channel function. These results suggest that iron oxide nanoparticles may affect T cell function by disturbing the activity of Kv1.3 channels. Further, the suppressing effects of Fe2O3-NPs on the expressions of certain inflammatory cytokines and interferon responsive genes suggest that iron

  5. Investigation on X-Radiation for 126 kV Vacuum Interrupters

    NASA Astrophysics Data System (ADS)

    Yan, Jing; Liu, Zhiyuan; Geng, Yingsan; Zhang, Sheng; Zhang, Yingyao

    2016-05-01

    When subjected to high voltages between opened contacts, vacuum interrupters may emit X-rays. In order to ensure that these are of an acceptable level, vacuum interrupters should comply with the limits for X-ray emission and the test procedures to be carried out to verify this based on relevant standards and specifications. In this paper, a comprehensive experimental study has been performed for 126 kV vacuum interrupters used in a transmission system to understand the X-radiation level and its influence by three main parameters, namely applied power-frequency voltage, contact gap and power-frequency voltage conditioning. The radiation instrument is an FJ347 radiometer and the X-radiation dose was measured at the power-frequency test voltage. These tests demonstrated that the X-radiation emission level for a 126 kV vacuum interrupter did not exceed the following: 5 μSv per hour at a rated voltage of 126 kV and 150 μSv per hour at a power-frequency voltage of 230 kV at 1 m distance. The X-radiation dose increased with the applied power-frequency voltage increasing and decreased with the contact gap increasing. The X-radiation dose for 126 kV vacuum interrupters decreased by 57% after the conditioning procedure with a certain power-frequency voltage. During the conditioning procedure, the average value of the X-radiation dose was 4.49 mSv, which means if a professional conditions 180 interrupters per year, it will be safe at the 6.4 m distance. supported by National Key Basic Research Program of China (973 Program) (No. 2015CB251002)

  6. Effects of Temperature on Heteromeric Kv11.1a/1b and Kv11.3 Channels.

    PubMed

    Mauerhöfer, Maike; Bauer, Christiane K

    2016-08-01

    Kv11.1 channels are crucial in cardiac physiology, and there is increasing evidence of physiological roles of different Kv11 channels outside the heart. The HERG (human Kv11.1a) channel has previously been shown to carry substantially more current at elevated temperatures, and we have now comparably investigated the temperature dependence of neuronal Kv11.3 channels and the more ubiquitous heteromeric Kv11.1a/1b channels. Transiently expressed rat Kv11 channels were studied at 21°C, 30°C, and 35°C. At near-physiological temperature, the maximal sustained outward current density was almost three times the mean value obtained at room temperature for Kv11.1a/1b, and increased by ∼150% for Kv11.3. For both channels, reduced inactivation contributed to the current increase at higher temperature. Elevated temperature moved Kv11.1a/1b isochronal activation curves to more negative potentials, but shifted the potential of half-maximal Kv11.3 channel activation to more depolarized values and reduced its voltage sensitivity. Thus, increased temperature stabilized the open state over the closed state of Kv11.1a/1b channels and exerted the opposite effect on Kv11.3 channel activation. Both Kv11 channels exhibited an overall high temperature sensitivity of most gating parameters, with remarkably high Q10 factors of ∼5 for the rate of Kv11.1a/1b activation. The Q10 factors for Kv11.3 gating were more uniform, but still higher for activation than for inactivation kinetics. The results demonstrate that characteristic differences between Kv11.1a/1b and Kv11.3 determined at room temperature do not necessarily apply to physiological conditions. The data provided here can aid in the design of models that will enhance our understanding of the role of Kv11 currents in excitable cells. PMID:27508435

  7. Myelinating Schwann cells determine the internodal localization of Kv1.1, Kv1.2, Kvbeta2, and Caspr.

    PubMed

    Arroyo, E J; Xu, Y T; Zhou, L; Messing, A; Peles, E; Chiu, S Y; Scherer, S S

    1999-01-01

    We examined the localization of Caspr and the K(+) channels Kv1.1 and Kv1.2, all of which are intrinsic membrane proteins of myelinated axons in the PNS. Caspr is localized to the paranode; Kv1. 1, Kv1.2 and their beta2 subunit are localized to the juxtaparanode. Throughout the internodal region, a strand of Caspr staining is flanked by a double strand of Kv1.1/Kv1.2/Kvbeta2 staining. This tripartite strand apposes the inner mesaxon of the myelin sheath, and forms a circumferential ring that apposes the innermost aspect of Schmidt-Lanterman incisures. The localization of Caspr and Kv1.2 are not disrupted in mice with null mutations of the myelin associated glycoprotein, connexin32, or Kv1.1 genes. At all of these locations, Caspr and Kv1.1/Kv1.2/Kvbeta2 define distinct but interrelated domains of the axonal membrane that appear to be organized by the myelin sheath. PMID:10739575

  8. 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

  9. 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

  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. 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

  12. 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.

  13. Development of molded joints and terminals for 230-kV extruded cross-linked polyethylene (XLPE) insulated cable. Final report

    SciTech Connect

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

    1985-04-01

    The reliability of extruded-dielectric transmission systems depends to a great extent on the quality of joints and terminals. Detailed procedures developed in this study for field-molding high-stress 230-kV cable joints can ensure the stability of critical interfaces over many years.

  14. Expression and localization of Kv1 potassium channels in rat dorsal and ventral spinal roots.

    PubMed

    Utsunomiya, Iku; Yoshihashi, Eikichi; Tanabe, Shinya; Nakatani, Yoshihiko; Ikejima, Hideaki; Miyatake, Tadashi; Hoshi, Keiko; Taguchi, Kyoji

    2008-03-01

    We investigated the expression and localization of Kv1 channels in dorsal spinal roots (DRs) and ventral spinal roots (VRs) in rats. Among Kv1.1-1.6 tested by RT-PCR, mRNAs of Kv1.1, 1.2, and 1.5 were moderately expressed, those of Kv1.3 and Kv1.6 were weakly expressed, and that of Kv1.4 was hardly expressed at all in both DRs and VRs, whereas all six mRNAs were detected in spinal cord. Western blotting revealed that the major immunoreactive proteins were Kv1.1 and Kv1.2 in both DRs and VRs. Quantitative analysis indicated that levels of Kv1.1 and Kv1.2 protein were significantly higher in DRs than VRs. Immunohistochemical examination showed that Kv1.1 and Kv1.2 were colocalized in juxtaparanodal regions of axons in both DRs and VRs. Finally, immunoprecipitation experiments revealed that Kv1.1 and Kv1.2 were coassembled. These findings indicate that Kv1 subtypes in DRs and VRs are somewhat different from those in spinal cord, and that the numbers of Kv1.1 and Kv1.2 channels are higher in DRs than VRs. PMID:18053989

  15. Solution of K-V envelope equations

    SciTech Connect

    Anderson, O.A.

    1995-04-01

    The envelope equations for a KV beam with space charge have been analyzed systematically by an e expansion followed by integrations. The focusing profile as a function of axial length is assumed to be symmetric but otherwise arbitrary. Given the bean current, emittance, and peak focusing field, we find the envelopes a(s) and b(s) and obtain , a{sub max}, {sigma}, and {sigma}{sub 0}. Explicit results are presented for various truncations of the expansion. The zeroth order results correspond to those from the well-known smooth approximation; the same convenient format is retained for the higher order cases. The first order results, involving single correction terms, give 3--10 times better accuracy and are good to {approximately}1% at {sigma}{sub 0} = 70{degree}. Third order gives a factor of 10--30 improvement over the smooth approximation and derived quantities accurate to {approximately}1% at {sigma}{sub 0} = 112 {degree}. The first order expressions are convenient design tools. They lend themselves to variable energy problems and have been applied to the design, construction, and testing of ESQ accelerators at LBL.

  16. Macroporous silicon membranes as electron and x-ray transmissive windows

    SciTech Connect

    Schilling, J.; Scherer, A.; Goesele, U.; Kolbe, M.

    2004-08-16

    Macroporous silicon membranes are fabricated whose pores are terminated with 60 nm thin silicon dioxide shells. The transmission of electrons with energies of 5 kV-25 kV through these membranes was investigated reaching a maximum of 22% for 25 kV. Furthermore, the transmission of electromagnetic radiation ranging from the far-infrared to the x-ray region was determined. The results suggest the application of the membrane as window material for electron optics and energy dispersive x-ray detectors.

  17. 78 FR 50405 - Amended Application for Presidential Permit; Northern Pass Transmission LLC

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-19

    ..., maintain, and connect an electric transmission line across the United States border with Canada. DATES... transmission line that would originate at an HVDC converter station to be constructed at the Des Cantons... portion of the proposed Project would be a single circuit 300 kilovolt (kV) HVDC transmission line...

  18. 75 FR 69990 - Application for Presidential Permit; Northern Pass Transmission LLC

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-16

    ... transmission line across the United States border with Canada. DATES: Comments, protests, or requests to... proposed international transmission line would originate at a high-voltage direct current (HVDC) converter... kilovolt (kV) HVDC overhead electric transmission line would extend southward in Province of Quebec...

  19. 200-kV active optical fiber voltage transformer

    NASA Astrophysics Data System (ADS)

    Xu, Yan; Luo, Sunan; Ye, Miaoyuan

    1999-02-01

    The report describes a 220kV Active Optical Fiber Voltage Transformer (AOVT). The transformer is different from the passive optical fiber voltage transformer, for no optical crystal is used in the 220kV AOVT. Its principle is that a low voltage is divided for the 220kV high voltage by a capacitive divider and then is converted into a digital signal. The optical fiber is used to transfer the measured digital signal and control signal. The 220kV AOVT consists of an outdoors-high voltage measurement unit and an indoors low voltage metering and controlling unit. The optical fiber connects these units. The low voltage is effectively isolated from the high voltage by means of the optical fiber and a special power supply method which is specially designed for the outdoor high voltage unit. As a result, the safe protection is reliable for the indoor low voltage equipment and the operation staff. Compared to the conventional voltage transformer, the advantages of the 220kV AOVT are high accuracy, low cost, excellent dynamic characteristics and immunity from electromagnetic interference. The 220kV AOVT has been tested, and its accuracy could achieve +/- 0.2 percent.

  20. Caveolin interaction governs Kv1.3 lipid raft targeting.

    PubMed

    Pérez-Verdaguer, Mireia; Capera, Jesusa; Martínez-Mármol, Ramón; Camps, Marta; Comes, Núria; Tamkun, Michael M; Felipe, Antonio

    2016-03-02

    The spatial localization of ion channels at the cell surface is crucial for their functional role. Many channels localize in lipid raft microdomains, which are enriched in cholesterol and sphingolipids. Caveolae, specific lipid rafts which concentrate caveolins, harbor signaling molecules and their targets becoming signaling platforms crucial in cell physiology. However, the molecular mechanisms involved in such spatial localization are under debate. Kv1.3 localizes in lipid rafts and participates in the immunological response. We sought to elucidate the mechanisms of Kv1.3 surface targeting, which govern leukocyte physiology. Kv1 channels share a putative caveolin-binding domain located at the intracellular N-terminal of the channel. This motif, lying close to the S1 transmembrane segment, is situated near the T1 tetramerization domain and the determinants involved in the Kvβ subunit association. The highly hydrophobic domain (FQRQVWLLF) interacts with caveolin 1 targeting Kv1.3 to caveolar rafts. However, subtle variations of this cluster, putative ancillary associations and different structural conformations can impair the caveolin recognition, thereby altering channel's spatial localization. Our results identify a caveolin-binding domain in Kv1 channels and highlight the mechanisms that govern the regulation of channel surface localization during cellular processes.

  1. 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

  2. Citizens, farmers fight huge transmission lines

    SciTech Connect

    Brummer, J.

    1982-02-01

    Opposition to high tension power lines with a 20-story towers is growing as coalitions of farmers and advocates of safe energy respond with legal intervention and sabotage, and sometimes with success. Examples of citizen action are the efforts opposing a 450 kilovolt direct current line connecting the US with Quebec Hydro and another opposing a 500 kilovolt alternating current line from Georgia Power Co.'s nuclear plants to Florida. The opposition derives partly from evidence of health hazards to humans and adverse effects on livestock. High voltage lines are felt to symbolize a utility and regulatory failure to assess the recent decline in power demand. It is stated that administration efforts to outlaw organized resistence will not deter the opposition, which cites instances of ground shock, aborted and stillborn cattle, physical irritants, and other phenomena. The General Assembly to Stop the Powerline (GASP) objects to the guinea pig position forced upon residents by the utilities. 6 references. (DCK)

  3. 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

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

    PubMed

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

    2007-06-15

    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 approximately 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 approximately 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.

  5. 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.

  6. The pore region of the Kv1.2alpha subunit is an important component of recombinant Kv1.2 channel oxygen sensitivity.

    PubMed

    Conforti, Laura; Takimoto, Koichi; Petrovic, Milan; Pongs, Olaf; Millhorn, David

    2003-06-27

    Oxygen-sensitive K(+) channels are important elements in the cellular response to hypoxia. Although much progress has been made in identifying their molecular composition, the structural components associated to their O(2)-sensitivity are not yet understood. Recombinant Kv1.2 currents expressed in Xenopus oocytes are inhibited by a decrease in O(2) availability. On the contrary, heterologous Kv2.1 channels are O(2)-insensitive. To elucidate the protein segment responsible for the O(2)-sensitivity of Kv1.2 channels, we analyzed the response to anoxia of Kv1.2/Kv2.1 chimeric channels. Expression of chimeric Kv2.1 channels each containing the S4, the S1-S3 or the S6-COOH segments of Kv1.2 polypeptide resulted in a K(+) current insensitive to anoxia. In contrast, transferring the S5-S6 segment of Kv1.2 into Kv2.1 produced an O(2)-sensitive K(+) current. Finally, mutating a redox-sensitive methionine residue (M380) of Kv1.2 polypeptide did not affect O(2)-sensitivity. Thus, the pore and its surrounding regions of Kv1.2 polypeptide confer its hypoxic inhibition. This response is independent on the redox modulation of methionine residues in this protein segment. PMID:12804584

  7. Alternative splicing modulates Kv channel clustering through a molecular ball and chain mechanism

    NASA Astrophysics Data System (ADS)

    Zandany, Nitzan; Marciano, Shir; Magidovich, Elhanan; Frimerman, Teddy; Yehezkel, Rinat; Shem-Ad, Tzilhav; Lewin, Limor; Abdu, Uri; Orr, Irit; Yifrach, Ofer

    2015-03-01

    Ion channel clustering at the post-synaptic density serves a fundamental role in action potential generation and transmission. Here, we show that interaction between the Shaker Kv channel and the PSD-95 scaffold protein underlying channel clustering is modulated by the length of the intrinsically disordered C terminal channel tail. We further show that this tail functions as an entropic clock that times PSD-95 binding. We thus propose a ‘ball and chain’ mechanism to explain Kv channel binding to scaffold proteins, analogous to the mechanism describing channel fast inactivation. The physiological relevance of this mechanism is demonstrated in that alternative splicing of the Shaker channel gene to produce variants of distinct tail lengths resulted in differential channel cell surface expression levels and clustering metrics that correlate with differences in affinity of the variants for PSD-95. We suggest that modulating channel clustering by specific spatial-temporal spliced variant targeting serves a fundamental role in nervous system development and tuning.

  8. Design and Evaluation of 275 kV-3 kA HTS Power Cable

    NASA Astrophysics Data System (ADS)

    Yagi, M.; Mukoyama, S.; Mitsuhashi, T.; Jun, T.; Liu, J.; Nakayama, R.; Hayakawa, N.; Wang, X.; Ishiyama, A.; Amemiya, N.; Hasegawa, T.; Saitoh, T.; Ohkuma, T.; Maruyama, O.

    A 275 kV 3 kA high temperature superconducting (HTS) cable has been developed in the Materials & Power Applications of Coated Conductors (M-PACC) project. The cable is expected to be put to practical use as the backbone power line in the future because the capacity of 1.5 GW is about the same as overhead transmission lines. The 30 m cable has been designed on the basis of design values that had been obtained by various voltage tests, AC loss measurement tests, short circuit tests, and other elementary tests. Cable insulation was determined by the design stresses and test conditions based on IEC, JEC (Japan electrical standards), and other HTS demonstrations. This cable was also designed to withstand the short circuit test of 63 kA for 0.6 seconds and to have low losses, including AC loss and dielectric loss of 0.8 W/m at 3kA, 275 kV. Based on the design, a 30 m cable was manufactured, and short samples during this manufacturing process were confirmed to have the designed characteristics. Furukawa Electric prepared a demonstration of the 30 m cable with two terminations and a cable joint. The long-term test under a current of 3 kA, and test voltage determined from 30 years of insulation degradation has been conducted since November 2012 at Shenyang in China.

  9. Calculation of geomagnetically induced currents in the 400 kV power grid in southern Sweden

    NASA Astrophysics Data System (ADS)

    Wik, M.; Viljanen, A.; Pirjola, R.; Pulkkinen, A.; Wintoft, P.; Lundstedt, H.

    2008-07-01

    Sweden has experienced many geomagnetically induced current (GIC) events in the past, which is obviously due to the high-latitude location of the country. The largest GIC, almost 300 A, was measured in southern Sweden in the earthing lead of a 400 kV transformer neutral during the magnetic storm on 6 April 2000. On 30 October 2003, the city of Malmö at the southern coast suffered from a power blackout caused by GIC, leaving 50,000 customers without electricity for about 20-50 min. We have developed a model that enables calculation of GIC in the southern Swedish 400 kV power grid. This work constitutes the first modeling effort of GIC in Sweden. The model is divided into two parts. The electric field is first derived using a ground conductivity model and geomagnetic recordings from nearby stations. The conductivity model is determined from a least squares fit between measured and calculated GIC. GIC are calculated using a power grid model consisting of the topology of the system and of the transformer, transmission line, and station earthing resistances as well as of the coordinates of the stations. To validate the model, we have compared measured and calculated GIC from one site. In total, 24 events in 1998 to 2000 were used. In general the agreement is satisfactory as the correct GIC order of magnitude is obtained by the model, which is usually enough for engineering applications.

  10. Chromatic Aberration Correction for Atomic Resolution TEM Imaging from 20 to 80 kV

    NASA Astrophysics Data System (ADS)

    Linck, Martin; Hartel, Peter; Uhlemann, Stephan; Kahl, Frank; Müller, Heiko; Zach, Joachim; Haider, Max.; Niestadt, Marcel; Bischoff, Maarten; Biskupek, Johannes; Lee, Zhongbo; Lehnert, Tibor; Börrnert, Felix; Rose, Harald; Kaiser, Ute

    2016-08-01

    Atomic resolution in transmission electron microscopy of thin and light-atom materials requires a rigorous reduction of the beam energy to reduce knockon damage. However, at the same time, the chromatic aberration deteriorates the resolution of the TEM image dramatically. Within the framework of the SALVE project, we introduce a newly developed Cc/Cs corrector that is capable of correcting both the chromatic and the spherical aberration in the range of accelerating voltages from 20 to 80 kV. The corrector allows correcting axial aberrations up to fifth order as well as the dominating off-axial aberrations. Over the entire voltage range, optimum phase-contrast imaging conditions for weak signals from light atoms can be adjusted for an optical aperture of at least 55 mrad. The information transfer within this aperture is no longer limited by chromatic aberrations. We demonstrate the performance of the microscope using the examples of 30 kV phase-contrast TEM images of graphene and molybdenum disulfide, showing unprecedented contrast and resolution that matches image calculations.

  11. 69 kV shunt capacitor bank specification considerations

    SciTech Connect

    Fenner, G.E. )

    1992-01-01

    PSI has standardized on the 69 kv ungrounded star, 7.2 mvar or multiple of the 7.2 mvar shunt capacitor bank for var control. This document defines the considerations to be addressed when specifying a 69 kv ungrounded capacitor bank and for providing suitable protection. The design goal is to provide a bank that is reliable and meets operational requirements at minimum cost with standard components. The bank components will be discussed separately. This paper defines the considerations for specifying capacitor banks to minimize cost, improve reliability and help standardize design. The components making up the bank will be individually discussed with special emphasis on the protection and control.

  12. 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.

  13. 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.

  14. 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.

  15. Stromatoxin-sensitive, heteromultimeric Kv2.1/Kv9.3 channels contribute to myogenic control of cerebral arterial diameter.

    PubMed

    Zhong, Xi Zoë; Abd-Elrahman, Khaled S; Liao, Chiu-Hsiang; El-Yazbi, Ahmed F; Walsh, Emma J; Walsh, Michael P; Cole, William C

    2010-11-15

    Cerebral vascular smooth muscle contractility plays a crucial role in controlling arterial diameter and, thereby, blood flow regulation in the brain. A number of K(+) channels have been suggested to contribute to the regulation of diameter by controlling smooth muscle membrane potential (E(m)) and Ca(2+) influx. Previous studies indicate that stromatoxin (ScTx1)-sensitive, Kv2-containing channels contribute to the control of cerebral arterial diameter at 80 mmHg, but their precise role and molecular composition were not determined. Here, we tested if Kv2 subunits associate with 'silent' subunits from the Kv5, Kv6, Kv8 or Kv9 subfamilies to form heterotetrameric channels that contribute to control of diameter of rat middle cerebral arteries (RMCAs) over a range of intraluminal pressure from 10 to 100 mmHg. The predominant mRNAs expressed by RMCAs encode Kv2.1 and Kv9.3 subunits. Co-localization of Kv2.1 and Kv9.3 proteins at the plasma membrane of dissociated single RMCA myocytes was detected by proximity ligation assay. ScTx1-sensitive native current of RMCA myocytes and Kv2.1/Kv9.3 currents exhibited functional identity based on the similarity of their deactivation kinetics and voltage dependence of activation that were distinct from those of homomultimeric Kv2.1 channels. ScTx1 treatment enhanced the myogenic response of pressurized RMCAs between 40 and 100 mmHg, but this toxin also caused constriction between 10 and 40 mmHg that was not previously observed following inhibition of large conductance Ca(2+)-activated K(+) (BK(Ca)) and Kv1 channels. Taken together, this study defines the molecular basis of Kv2-containing channels and contributes to our understanding of the functional significance of their expression in cerebral vasculature. Specifically, our findings provide the first evidence of heteromultimeric Kv2.1/Kv9.3 channel expression in RMCA myocytes and their distinct contribution to control of cerebral arterial diameter over a wider range of E(m) and

  16. 77 FR 35366 - Albany-Eugene Transmission Line Rebuild Project

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-13

    ... Administration (BPA), Department of Energy (DOE). ACTION: Notice of Availability of Record of Decision (ROD..., based on the Albany-Eugene Transmission Line Rebuild Project (DOE/EIS-0457, March 2012). BPA has decided... will continue to operate at 115 kV. ADDRESSES: Copies of the ROD and EIS may be obtained by calling...

  17. 75 FR 16913 - Transmission Relay Loadability Reliability Standard

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-02

    ...\\ Transmission Relay Loadability Reliability Standard, Notice of Proposed Rulemaking, 74 FR 35830 (Jul. 21, 2009... adequately address the Commission's underlying concern or goal as efficiently and effectively as the... meet this goal, the Commission stated that the process for identifying critical 100 kV-200...

  18. Pharmacological characteristics of Kv1.1- and Kv1.2-containing channels are influenced by the stoichiometry and positioning of their α subunits.

    PubMed

    Al-Sabi, Ahmed; Kaza, Seshu Kumar; Dolly, J Oliver; Wang, Jiafu

    2013-08-15

    Voltage-sensitive neuronal Kv1 channels composed of four α subunits and four associated auxiliary β subunits control neuronal excitability and neurotransmission. Limited information exists on the combinations of α subunit isoforms (i.e. Kv1.1-1.6) or their positions in the oligomers, and how these affect sensitivity to blockers. It is known that TEA (tetraethylammonium) inhibits Kv1.1 channels largely due to binding a critical tyrosine (Tyr379) in the pore, whereas Val381 at the equivalent location in Kv1.2 makes it insensitive. With the eventual aim of developing blockers for therapeutic purposes, Kv1.1 and 1.2 α subunit genes were concatenated to form combinations representing those in central neurons, followed by surface expression in HEK (human embryonic kidney)-293 cells as single-chain functional proteins. Patch-clamp recordings demonstrated the influences of the ratios and positioning of these α subunits on the biophysical and pharmacological properties of oligomeric K+ channels. Raising the ratio of Kv1.1 to Kv1.2 in Kv1.2-1.2-1.1-1.2 led to the resultant channels being more sensitive to TEA and also affected their biophysical parameters. Moreover, mutagenesis of one or more residues in the first Kv1.2 to resemble those in Kv1.1 increased TEA sensitivity only when it is adjacent to a Kv1.1 subunit, whereas placing a non-interactive subunit between these two diminished susceptibility. The findings of the present study support the possibility of α subunits being precisely arranged in Kv1 channels, rather than being randomly assembled. This is important in designing drugs with abilities to inhibit particular oligomeric Kv1 subtypes, with the goal of elevating neuronal excitability and improving neurotransmission in certain diseases.

  19. Evaluation of HVDC cables for the St. Lawrence River crossing of Hydro-Quebec's 500 kV DC line. Part 2; Cable testing facility for dielectric and accelerated aging

    SciTech Connect

    Trinh, N.G.; Couderc, D.; Faucher, P.; Chaaban, M.; Belec, M.; Leduc, J. )

    1992-04-01

    This paper describes the new cable testing facility at IREQ for long-term accelerated aging tests on HV cables. This test facility was required as part of an extensive program to evaluate the high-voltage cables for the river crossing of Hydro-Quebec's new transmission lines rated 800 kV AC and {plus minus}500 kV DC. The first application was for the evaluation of self-contained oil-filled (SCOF) cables for the St. Lawrence river crossing of the {plus minus}500 kV Quebec-New England HVDC power transmission system. The paper also describes the specific dielectric constraints resulting from the insertion of a short length of cable into a long line and, also, the circuits developed for the special tests, which reproduce the specific cable test conditions.

  20. A Novel Electrical Insulating Material for 275 kV High-Voltage HTS Cable with Low Dielectric Loss

    NASA Astrophysics Data System (ADS)

    Hayakawa, N.; Nishimachi, S.; Maruyama, O.; Ohkuma, T.; Liu, J.; Yagi, M.

    2014-05-01

    In the case of high temperature superconducting (HTS) power transmission cables at high voltage operation, the electrical insulation technique in consideration of the dielectric loss reduction becomes crucial. In this paper, we focused on a Tyvek/polyethylene (PE) sheet, instead of the conventional polypropylene laminated paper (PPLP). We obtained the dielectric characteristics (epsilonr, tanδ) and partial discharge inception strength (PDIE) of PPLP, Tyvek and Tyvek/PE. We pointed out that the dielectric loss of 275 kV HTS cable with Tyvek/PE insulation will be reduced to 21 % of that with PPLP, and the total electrical loss including the AC loss will be reduced to 41 %.

  1. A compact 300 kV solid-state high-voltage nanosecond generator for dielectric wall accelerator.

    PubMed

    Shen, Yi; Wang, Wei; Liu, Yi; Xia, Liansheng; Zhang, Huang; Pan, Haifeng; Zhu, Jun; Shi, Jinshui; Zhang, Linwen; Deng, Jianjun

    2015-05-01

    Compact solid-state system is the main development trend in pulsed power technologies. A compact solid-state high-voltage nanosecond pulse generator with output voltage of 300 kV amplitude, 10 ns duration (FWHM), and 3 ns rise-time was designed for a dielectric wall accelerator. The generator is stacked by 15 planar-plate Blumlein pulse forming lines (PFL). Each Blumlein PFL consists of two solid-state planar transmission lines, a GaAs photoconductive semiconductor switch, and a laser diode trigger. The key components of the generator and the experimental results are reported in this paper. PMID:26026561

  2. A compact 300 kV solid-state high-voltage nanosecond generator for dielectric wall accelerator

    SciTech Connect

    Shen, Yi; Wang, Wei; Liu, Yi; Xia, Liansheng Zhang, Huang; Pan, Haifeng; Zhu, Jun; Shi, Jinshui; Zhang, Linwen; Deng, Jianjun

    2015-05-15

    Compact solid-state system is the main development trend in pulsed power technologies. A compact solid-state high-voltage nanosecond pulse generator with output voltage of 300 kV amplitude, 10 ns duration (FWHM), and 3 ns rise-time was designed for a dielectric wall accelerator. The generator is stacked by 15 planar-plate Blumlein pulse forming lines (PFL). Each Blumlein PFL consists of two solid-state planar transmission lines, a GaAs photoconductive semiconductor switch, and a laser diode trigger. The key components of the generator and the experimental results are reported in this paper.

  3. A compact 300 kV solid-state high-voltage nanosecond generator for dielectric wall accelerator

    NASA Astrophysics Data System (ADS)

    Shen, Yi; Wang, Wei; Liu, Yi; Xia, Liansheng; Zhang, Huang; Pan, Haifeng; Zhu, Jun; Shi, Jinshui; Zhang, Linwen; Deng, Jianjun

    2015-05-01

    Compact solid-state system is the main development trend in pulsed power technologies. A compact solid-state high-voltage nanosecond pulse generator with output voltage of 300 kV amplitude, 10 ns duration (FWHM), and 3 ns rise-time was designed for a dielectric wall accelerator. The generator is stacked by 15 planar-plate Blumlein pulse forming lines (PFL). Each Blumlein PFL consists of two solid-state planar transmission lines, a GaAs photoconductive semiconductor switch, and a laser diode trigger. The key components of the generator and the experimental results are reported in this paper.

  4. 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…

  5. Extracellular potassium inhibits Kv7.1 potassium channels by stabilizing an inactivated state.

    PubMed

    Larsen, Anders Peter; Steffensen, Annette Buur; Grunnet, Morten; Olesen, Søren-Peter

    2011-08-17

    Kv7.1 (KCNQ1) channels are regulators of several physiological processes including vasodilatation, repolarization of cardiomyocytes, and control of secretory processes. A number of Kv7.1 pore mutants are sensitive to extracellular potassium. We hypothesized that extracellular potassium also modulates wild-type Kv7.1 channels. The Kv7.1 currents were measured in Xenopus laevis oocytes at different concentrations of extracellular potassium (1-50 mM). As extracellular potassium was elevated, Kv7.1 currents were reduced significantly more than expected from theoretical calculations based on the Goldman-Hodgkin-Katz flux equation. Potassium inhibited the steady-state current with an IC(50) of 6.0 ± 0.2 mM. Analysis of tail-currents showed that potassium increased the fraction of channels in the inactivated state. Similarly, the recovery from inactivation was slowed by potassium, suggesting that extracellular potassium stabilizes an inactivated state in Kv7.1 channels. The effect of extracellular potassium was absent in noninactivating Kv7.1/KCNE1 and Kv7.1/KCNE3 channels, further supporting a stabilized inactivated state as the underlying mechanism. Interestingly, coexpression of Kv7.1 with KCNE2 did not attenuate the inhibition by potassium. In a number of other Kv channels, including Kv1.5, Kv4.3, and Kv7.2-5 channels, currents were only minimally reduced by an increase in extracellular potassium as expected. These results show that extracellular potassium modulates Kv7.1 channels and suggests that physiological changes in potassium concentrations may directly control the function of Kv7.1 channels. This may represent a novel regulatory mechanism of excitability and of potassium transport in tissues expressing Kv7.1 channels. PMID:21843472

  6. 29 CFR 1926.1409 - Power line safety (over 350 kV).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 8 2012-07-01 2012-07-01 false Power line safety (over 350 kV). 1926.1409 Section 1926... Construction § 1926.1409 Power line safety (over 350 kV). The requirements of § 1926.1407 and § 1926.1408 apply to power lines over 350 kV except: (a) For power lines at or below 1000 kV, wherever the distance...

  7. 29 CFR 1926.1409 - Power line safety (over 350 kV).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 8 2014-07-01 2014-07-01 false Power line safety (over 350 kV). 1926.1409 Section 1926... Construction § 1926.1409 Power line safety (over 350 kV). The requirements of § 1926.1407 and § 1926.1408 apply to power lines over 350 kV except: (a) For power lines at or below 1000 kV, wherever the distance...

  8. 29 CFR 1926.1409 - Power line safety (over 350 kV).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 8 2011-07-01 2011-07-01 false Power line safety (over 350 kV). 1926.1409 Section 1926... Construction § 1926.1409 Power line safety (over 350 kV). The requirements of § 1926.1407 and § 1926.1408 apply to power lines over 350 kV except: (a) For power lines at or below 1000 kV, wherever the distance...

  9. 29 CFR 1926.1409 - Power line safety (over 350 kV).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 8 2013-07-01 2013-07-01 false Power line safety (over 350 kV). 1926.1409 Section 1926... Construction § 1926.1409 Power line safety (over 350 kV). The requirements of § 1926.1407 and § 1926.1408 apply to power lines over 350 kV except: (a) For power lines at or below 1000 kV, wherever the distance...

  10. 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)

  11. IA Channels Encoded by Kv1.4 and Kv4.2 Regulate Circadian Period of PER2 Expression in the Suprachiasmatic Nucleus.

    PubMed

    Granados-Fuentes, Daniel; Hermanstyne, Tracey O; Carrasquillo, Yarimar; Nerbonne, Jeanne M; Herzog, Erik D

    2015-10-01

    Neurons in the suprachiasmatic nucleus (SCN), the master circadian pacemaker in mammals, display daily rhythms in electrical activity with more depolarized resting potentials and higher firing rates during the day than at night. Although these daily variations in the electrical properties of SCN neurons are required for circadian rhythms in physiology and behavior, the mechanisms linking changes in neuronal excitability to the molecular clock are not known. Recently, we reported that mice deficient for either Kcna4 (Kv1.4(-/-)) or Kcnd2 (Kv4.2(-/-); but not Kcnd3, Kv4.3(-/-)), voltage-gated K(+) (Kv) channel pore-forming subunits that encode subthreshold, rapidly activating, and inactivating K(+) currents (IA), have shortened (0.5 h) circadian periods in SCN firing and in locomotor activity compared with wild-type (WT) mice. In the experiments here, we used a mouse (Per2(Luc)) line engineered with a bioluminescent reporter construct, PERIOD2::LUCIFERASE (PER2::LUC), replacing the endogenous Per2 locus, to test the hypothesis that the loss of Kv1.4- or Kv4.2-encoded IA channels also modifies circadian rhythms in the expression of the clock protein PERIOD2 (PER2). We found that SCN explants from Kv1.4(-/-)Per2(Luc) and Kv4.2(-/-) Per2(Luc), but not Kv4.3(-/-)Per2(Luc), mice have significantly shorter (by approximately 0.5 h) circadian periods in PER2 rhythms, compared with explants from Per2(Luc) mice, revealing that the membrane properties of SCN neurons feedback to regulate clock (PER2) expression. The combined loss of both Kv1.4- and Kv4.2-encoded IA channels in Kv1.4(-/-)/Kv4.2(-/-)Per2(Luc) SCN explants did not result in any further alterations in PER2 rhythms. Interestingly, however, mice lacking both Kv1.4 and Kv4.2 show a striking (approximately 1.8 h) advance in their daily activity onset in a light cycle compared with WT mice, suggesting additional roles for Kv1.4- and Kv4.2-encoded IA channels in controlling the light-dependent responses of neurons within

  12. Potential role for kv3.1b channels as oxygen sensors.

    PubMed

    Osipenko, O N; Tate, R J; Gurney, A M

    2000-03-17

    Hypoxia inhibits voltage-gated K channels in pulmonary artery smooth muscle (PASM). This is thought to contribute to hypoxic pulmonary vasoconstriction by promoting membrane depolarization, Ca(2+) influx, and contraction. Several of the K-channel subtypes identified in pulmonary artery have been implicated in the response to hypoxia, but contradictory evidence clouds the identity of the oxygen-sensing channels. Using patch-clamp techniques, this study investigated the effect of hypoxia on recombinant Kv1 channels previously identified in pulmonary artery (Kv1.1, Kv1.2, and Kv1.5) and Kv3.1b, which has similar kinetic and pharmacological properties to native oxygen-sensitive currents. Hypoxia failed to inhibit any Kv1 channel, but it inhibited Kv3.1b channels expressed in L929 cells, as shown by a reduction of whole-cell current and single-channel activity, without affecting unitary conductance. Inhibition was retained in excised membrane patches, suggesting a membrane-delimited mechanism. Using reverse transcription-polymerase chain reaction and immunocytochemistry, Kv3.1b expression was demonstrated in PASM cells. Moreover, hypoxia inhibited a K(+) current in rabbit PASM cells in the presence of charybdotoxin and capsaicin, which preserve Kv3.1b while blocking most other Kv channels, but not in the presence of millimolar tetraethylammonium ions, which abolish Kv3.1b current. Kv3.1b channels may therefore contribute to oxygen sensing in pulmonary artery.

  13. Supplement Analysis for the Transmission System Vegetation Management Program FEIS (DOE/EIS-0285/SA-127- Eugene-Alvey#2

    SciTech Connect

    Sherer, Brett M.

    2003-02-19

    BPA proposes to remove unwanted vegetation along the right-of-way, access roads, and around tower structures of the subject transmission line corridor that may impede the operation and maintenance of the identified transmission lines. BPA plans to conduct vegetation control with the goal of removing tall growing vegetation that is currently or will soon be a hazard to the transmission line. BPA’s overall goal is to have low-growing plant communities along the rights-of-way to control the development of potentially threatening vegetation. Vegetation Management for the Eugene-Alvey 115 kV transmission line from structure 7/1 through structure 12/2m, and along portions of the following adjacent transmission lines: Hawkins-Alvey 115KV and Alvey-Lane 115KV.

  14. Shingles Transmission

    MedlinePlus

    ... on Shingles Immunization Action Coalition Chickenpox Q&As Transmission Language: English Español (Spanish) Recommend on Facebook Tweet ... Prevention & Treatment Related Pages Preventing Varicella Zoster Virus Transmission in Healthcare Settings Related Links Medline Plus NIH ...

  15. Kv1.3 potassium channel mediates macrophage migration in atherosclerosis by regulating ERK activity.

    PubMed

    Kan, Xiao-Hong; Gao, Hai-Qing; Ma, Zhi-Yong; Liu, Lin; Ling, Ming-Ying; Wang, Yuan-Yuan

    2016-02-01

    Ion channels expressed in macrophages have been tightly related to atherosclerosis by coupling cellular function. How the voltage-gated potassium channels (Kv) affect macrophage migration remain unknown. The aim of our study is to investigate whether Kv1.3-ERK signaling pathway plays an important role in the process. We explored the expression of Kv1.3 in coronary atherosclerotic heart disease and found Kv1.3 channel was increased in acute coronary syndrome patients. Treatment of RAW264.7 cells with Kv1.3 small interfering RNA, suppressed cell migration. The expression of phosphorylated ERK1/2 also decreased after knockdown of Kv1.3. On the other hand, overexpression of Kv1.3 channel promoted cell migration and ERK1/2 phosphorylation. U-0126, the mitogen-activated protein kinase inhibitors, could reverse macrophage migration induced by Kv1.3 channel overexpression. Downregulation of Kv1.3 channel by siRNA could not further inhibit cell migration when cells were treated with U-0126. It means that ERK is downstream signal of Kv1.3 channel. We concluded that Kv1.3 may stimulate macrophage migration through the activation of ERK.

  16. Use of 100 kV versus 120 kV in cardiac dual source computed tomography: effect on radiation dose and image quality.

    PubMed

    Blankstein, Ron; Bolen, Michael A; Pale, Rodrigo; Murphy, Meagan K; Shah, Amar B; Bezerra, Hiram G; Sarwar, Ammar; Rogers, Ian S; Hoffmann, Udo; Abbara, Suhny; Cury, Ricardo C; Brady, Thomas J

    2011-04-01

    To evaluate the effective radiation dose and image quality resulting from use of 100 vs. 120 kV among patients referred for cardiac dual source CT exam (DSCT). Prospective data was collected on 294 consecutive patients referred for DSCT. For each scan, a physician specializing in cardiac CT chose all parameters including tube current and voltage, axial versus helical acquisition, and use of tube current modulation. Lower tube voltage was selected for thinner patients or when lower radiation was desired for younger patients, particularly females. For each study, image quality (IQ) was rated on a subjective IQ score and contrast (CNR) and signal-to-noise (SNR) ratios were calculated. Tube voltage of 100 kV was used for 77 (26%) exams while 120 kV was used for 217 (74%) exams. Use of 100 kV was more common in thinner patients (weight 166 lbs vs. 199 lbs, P < .001). The effective radiation dose for the 100 and 120 kV scans was 8.5 and 15.4 mSv respectively. Among scans utilizing 100 and 120 kV, there was no difference in exam indication, use of beta blockers, heart rate, scan length and use of radiation saving techniques such as prospective ECG triggering and tube current modulation. The IQ score was significantly higher for 100 kV scans. While 100 kV scans were found to have higher image noise then those utilizing 120 kV, the contrast-to-noise and signal-to-noise were significantly higher (SNR: 9.4 vs. 8.3, P = .02; CNR: 6.9 vs. 6.0, P = .02). In selected non-obese patients, use of low kV results in a substantial reduction of radiation dose and may result in improved image quality. These results suggest that low kV should be used more frequently in non-obese patients. PMID:20721630

  17. Inhibition of KV7 Channels Protects the Rat Heart against Myocardial Ischemia and Reperfusion Injury.

    PubMed

    Hedegaard, Elise R; Johnsen, Jacob; Povlsen, Jonas A; Jespersen, Nichlas R; Shanmuganathan, Jeffrey A; Laursen, Mia R; Kristiansen, Steen B; Simonsen, Ulf; Bøtker, Hans Erik

    2016-04-01

    The voltage-gated KV7 (KCNQ) potassium channels are activated by ischemia and involved in hypoxic vasodilatation. We investigated the effect of KV7 channel modulation on cardiac ischemia and reperfusion injury and its interaction with cardioprotection by ischemic preconditioning (IPC). Reverse-transcription polymerase chain reaction revealed expression of KV7.1, KV7.4, and KV7.5 in the left anterior descending rat coronary artery and all KV7 subtypes (KV7.1-KV7.5) in the left and right ventricles of the heart. Isolated hearts were subjected to no-flow global ischemia and reperfusion with and without IPC. Infarct size was quantified by 2,3,5-triphenyltetrazolium chloride staining. Two blockers of KV7 channels, XE991 [10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone] (10 µM) and linopirdine (10 µM), reduced infarct size and exerted additive infarct reduction to IPC. An opener of KV7 channels, flupirtine (10 µM) abolished infarct size reduction by IPC. Hemodynamics were measured using a catheter inserted in the left ventricle and postischemic left ventricular recovery improved in accordance with reduction of infarct size and deteriorated with increased infarct size. XE991 (10 µM) reduced coronary flow in the reperfusion phase and inhibited vasodilatation in isolated small branches of the left anterior descending coronary artery during both simulated ischemia and reoxygenation. KV7 channels are expressed in rat coronary arteries and myocardium. Inhibition of KV7 channels exerts cardioprotection and opening of KV7 channels abrogates cardioprotection by IPC. Although safety issues should be further addressed, our findings suggest a potential role for KV7 blockers in the treatment of ischemia-reperfusion injury. PMID:26869667

  18. A Quantitative Analysis of Neurons with Kv3 Potassium Channel Subunits–Kv3.1b and Kv3.2–in Macaque Primary Visual Cortex

    PubMed Central

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

    2010-01-01

    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 co-expression 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-ir neurons in macaque V1. We found that across the cortical layers ~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). 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. PMID:19634181

  19. Contributions of intracellular ions to kv channel voltage sensor dynamics.

    PubMed

    Goodchild, Samuel J; Fedida, David

    2012-01-01

    Voltage-sensing domains (VSDs) of Kv channels control ionic conductance through coupling of the movement of charged residues in the S4 segment to conformational changes at the cytoplasmic region of the pore domain, that allow K(+) ions to flow. Conformational transitions within the VSD are induced by changes in the applied voltage across the membrane field. However, several other factors not directly linked to the voltage-dependent movement of charged residues within the voltage sensor impact the dynamics of the voltage sensor, such as inactivation, ionic conductance, intracellular ion identity, and block of the channel by intracellular ligands. The effect of intracellular ions on voltage sensor dynamics is of importance in the interpretation of gating current measurements and the physiology of pore/voltage sensor coupling. There is a significant amount of variability in the reported kinetics of voltage sensor deactivation kinetics of Kv channels attributed to different mechanisms such as open state stabilization, immobilization, and relaxation processes of the voltage sensor. Here we separate these factors and focus on the causal role that intracellular ions can play in allosterically modulating the dynamics of Kv voltage sensor deactivation kinetics. These considerations are of critical importance in understanding the molecular determinants of the complete channel gating cycle from activation to deactivation.

  20. 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

  1. Coming: 12,600 megawatts at Itaipu Island

    SciTech Connect

    de Moraes, J.

    1983-08-01

    This paper describes the hydroelectric plant being constructed jointly by Brazil and Paraguay on Itaipu Island in the Parana River. The planned generating capacity of 12,600 MW will make the Itaipu plant the world's largest. It will employ the most powerful hydrogenerators and turbines yet built, the world's largest concentration of 500-kilovolt gas-insulated switchgear, the highest dc transmission voltages and power--600 kV and 6300 MW--ever used, about 1000 kilometers of 765-kV ac transmission, and an extensive computer-based digital supervisory system in which continuous diagnostic evaluation of equipment is emphasized. To maintain national standards, nine generators will operate at 60 hertz for Brazil and nine at 50 hertz for Paraguay. Initially, any excess electricity available from the Paraguay generators will be routed to Brazil, but Paraguay is ultimately expected to share in half the Itaipu generation. The paper discusses the plant from its original feasibility studies to the newly created technologies which its size necessitated. The environmental impact on forests, farmlands and wildlife resulting from the construction of the Itaipu dam and the loss of the 1400 square kilometers which it flooded--including the popular Seven Waterfalls--is addressed. References to other papers as well as a symposium on the Itaipu project are cited.

  2. 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

  3. 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.

  4. 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

  5. Kv2 dysfunction after peripheral axotomy enhances sensory neuron responsiveness to sustained input☆

    PubMed Central

    Tsantoulas, Christoforos; Zhu, Lan; Yip, Ping; Grist, John; Michael, Gregory J.; McMahon, Stephen B.

    2014-01-01

    Peripheral nerve injuries caused by trauma are associated with increased sensory neuron excitability and debilitating chronic pain symptoms. Axotomy-induced alterations in the function of ion channels are thought to largely underlie the pathophysiology of these phenotypes. Here, we characterise the mRNA distribution of Kv2 family members in rat dorsal root ganglia (DRG) and describe a link between Kv2 function and modulation of sensory neuron excitability. Kv2.1 and Kv2.2 were amply expressed in cells of all sizes, being particularly abundant in medium-large neurons also immunoreactive for neurofilament-200. Peripheral axotomy led to a rapid, robust and long-lasting transcriptional Kv2 downregulation in the DRG, correlated with the onset of mechanical and thermal hypersensitivity. The consequences of Kv2 loss-of-function were subsequently investigated in myelinated neurons using intracellular recordings on ex vivo DRG preparations. In naïve neurons, pharmacological Kv2.1/Kv2.2 inhibition by stromatoxin-1 (ScTx) resulted in shortening of action potential (AP) after-hyperpolarization (AHP). In contrast, ScTx application on axotomized neurons did not alter AHP duration, consistent with the injury-induced Kv2 downregulation. In accordance with a shortened AHP, ScTx treatment also reduced the refractory period and improved AP conduction to the cell soma during high frequency stimulation. These results suggest that Kv2 downregulation following traumatic nerve lesion facilitates greater fidelity of repetitive firing during prolonged input and thus normal Kv2 function is postulated to limit neuronal excitability. In summary, we have profiled Kv2 expression in sensory neurons and provide evidence for the contribution of Kv2 dysfunction in the generation of hyperexcitable phenotypes encountered in chronic pain states. PMID:24252178

  6. Recombinant Kv channels at the membrane of Escherichia coli bind specifically agitoxin2.

    PubMed

    Nekrasova, Oksana V; Ignatova, Anastasia A; Nazarova, Anna I; Feofanov, Alexey V; Korolkova, Yuliya V; Boldyreva, Elena F; Tagvei, Anna I; Grishin, Eugene V; Arseniev, Alexander S; Kirpichnikov, Mikhail P

    2009-03-01

    Potassium voltage-gated channels (Kv) are considered as molecular targets in a number of serious neuronal, immune, and cardiac disorders. Search for efficient low-molecular weight modulators of Kv channel function provides a basis for the development of an appropriate therapy for various Kv-mediated diseases. We report here on a new bacterial cell-based system, which is suitable for study of interactions between ligands and ligand-binding sites of eukaryotic Kv1.3 and Kv1.1 channels. To create this system, high-level expression of KcsA-Kv1.3 and KcsA-Kv1.1 hybrid proteins (ligand-binding sites of Kv1.3 or Kv1.1 fused with prokaryotic KcsA potassium channel) was achieved in the plasma membrane of Escherichia coli. An efficient procedure of E. coli conversion to intact spheroplasts was developed. We demonstrate that fluorescently labeled agitoxin 2 binds specifically to high-affinity and lower-affinity sites of KcsA-Kv1.3 and KcsA-Kv1.1, respectively, at the membrane of spheroplasts. Number of binding sites per cell is estimated to be (1.0 +/- 0.6) x 10(5) and (0.3 +/- 0.2) x 10(5) for KcsA-Kv1.3- and KcsA-Kv1.1-presenting cells, respectively, that allows reliable detection of ligand-receptor interactions by confocal laser scanning microscopy. This bacterial cell-based system is intended for screening of ligands to membrane-embedded pharmaceutical targets.

  7. Facsimile transmissions.

    PubMed

    Grant, A E

    1996-04-01

    Some provincial regulators of nursing are setting out professional standards for the use of facsimile transmissions. While the facsimile machine is a tool that can improve client care through the timely, accurate transmission of vital information, nurses should recognize the potential hazards. Clear policies and procedures for the usage and management of facsimile transmissions are necessary to ensure that legal and professional standards are met.

  8. Solid-State Fault Current Limiter Development : Design and Testing Update of a 15kV SSCL Power Stack

    SciTech Connect

    Dr. Ram Adapa; Mr. Dante Piccone

    2012-04-30

    ABSTRACT The Solid-State Fault Current Limiter (SSCL) is a promising technology that can be applied to utility power delivery systems to address the problem of increasing fault currents associated with load growth. As demand continues to grow, more power is added to utility system either by increasing generator capacity or by adding distributed generators, resulting in higher available fault currents, often beyond the capabilities of the present infrastructure. The SSCL is power-electronics based equipment designed to work with the present utility system to address this problem. The SSCL monitors the line current and dynamically inserts additional impedance into the line in the event of a fault being detected. The SSCL is based on a modular design and can be configured for 5kV through 69kV systems at nominal current ratings of 1000A to 4000A. Results and Findings This report provides the final test results on the development of 15kV class SSCL single phase power stack. The scope of work included the design of the modular standard building block sub-assemblies, the design and manufacture of the power stack and the testing of the power stack for the key functional tests of continuous current capability and fault current limiting action. Challenges and Objectives Solid-State Current Limiter technology impacts a wide spectrum of utility engineering and operating personnel. It addresses the problems associated with load growth both at Transmission and Distribution class networks. The design concept is pioneering in terms of developing the most efficient and compact power electronics equipment for utility use. The initial test results of the standard building blocks are promising. The independent laboratory tests of the power stack are promising. However the complete 3 phase system needs rigorous testing for performance and reliability. Applications, Values, and Use The SSCL is an intelligent power-electronics device which is modular in design and can provide current

  9. Transmission eigenvalues

    NASA Astrophysics Data System (ADS)

    Cakoni, Fioralba; Haddar, Houssem

    2013-10-01

    In inverse scattering theory, transmission eigenvalues can be seen as the extension of the notion of resonant frequencies for impenetrable objects to the case of penetrable dielectrics. The transmission eigenvalue problem is a relatively late arrival to the spectral theory of partial differential equations. Its first appearance was in 1986 in a paper by Kirsch who was investigating the denseness of far-field patterns for scattering solutions of the Helmholtz equation or, in more modern terminology, the injectivity of the far-field operator [1]. The paper of Kirsch was soon followed by a more systematic study by Colton and Monk in the context of developing the dual space method for solving the inverse scattering problem for acoustic waves in an inhomogeneous medium [2]. In this paper they showed that for a spherically stratified media transmission eigenvalues existed and formed a discrete set. Numerical examples were also given showing that in principle transmission eigenvalues could be determined from the far-field data. This first period of interest in transmission eigenvalues was concluded with papers by Colton et al in 1989 [3] and Rynne and Sleeman in 1991 [4] showing that for an inhomogeneous medium (not necessarily spherically stratified) transmission eigenvalues, if they existed, formed a discrete set. For the next seventeen years transmission eigenvalues were ignored. This was mainly due to the fact that, with the introduction of various sampling methods to determine the shape of an inhomogeneous medium from far-field data, transmission eigenvalues were something to be avoided and hence the fact that transmission eigenvalues formed at most a discrete set was deemed to be sufficient. In addition, questions related to the existence of transmission eigenvalues or the structure of associated eigenvectors were recognized as being particularly difficult due to the nonlinearity of the eigenvalue problem and the special structure of the associated transmission

  10. Evaluation of HVDC cables for the St. Lawrence crossing of Hydro-Quebec 500 kV DC Line. Part 1; Dielectric and accelerated aging tests on prototypes

    SciTech Connect

    Coudere, D.; Trinh, N.G.; Belec, M.; Chaaban, M.; Leduc, J.; Beausejour, Y. )

    1992-04-01

    This paper describes the dielectric and accelerated aging tests on prototype {plus minus}500 kV dc oil-filled self-contained cables. The extensive test program was required to evaluate the High-Voltage cables for the St. Lawrence river crossing of the {plus minus}500 kV Quebec-New England HVDC power transmission system. The paper relates the main elements of the test program. It describes the required insulation levels, the characteristics of the cables supplied by three different manufacturers, as well as the cables' installation for the type tests and accelerated aging tests. Details of the test program and procedures followed to carry out the tests are given. Findings of the tests are also reported.

  11. Transmission eigenvalues

    NASA Astrophysics Data System (ADS)

    Cakoni, Fioralba; Haddar, Houssem

    2013-10-01

    In inverse scattering theory, transmission eigenvalues can be seen as the extension of the notion of resonant frequencies for impenetrable objects to the case of penetrable dielectrics. The transmission eigenvalue problem is a relatively late arrival to the spectral theory of partial differential equations. Its first appearance was in 1986 in a paper by Kirsch who was investigating the denseness of far-field patterns for scattering solutions of the Helmholtz equation or, in more modern terminology, the injectivity of the far-field operator [1]. The paper of Kirsch was soon followed by a more systematic study by Colton and Monk in the context of developing the dual space method for solving the inverse scattering problem for acoustic waves in an inhomogeneous medium [2]. In this paper they showed that for a spherically stratified media transmission eigenvalues existed and formed a discrete set. Numerical examples were also given showing that in principle transmission eigenvalues could be determined from the far-field data. This first period of interest in transmission eigenvalues was concluded with papers by Colton et al in 1989 [3] and Rynne and Sleeman in 1991 [4] showing that for an inhomogeneous medium (not necessarily spherically stratified) transmission eigenvalues, if they existed, formed a discrete set. For the next seventeen years transmission eigenvalues were ignored. This was mainly due to the fact that, with the introduction of various sampling methods to determine the shape of an inhomogeneous medium from far-field data, transmission eigenvalues were something to be avoided and hence the fact that transmission eigenvalues formed at most a discrete set was deemed to be sufficient. In addition, questions related to the existence of transmission eigenvalues or the structure of associated eigenvectors were recognized as being particularly difficult due to the nonlinearity of the eigenvalue problem and the special structure of the associated transmission

  12. AQUIFER TRANSMISSIVITY

    EPA Science Inventory

    Evaluation of groundwater resources requires the knowledge of the capacity of aquifers to store and transmit ground water. This requires estimates of key hydraulic parameters, such as the transmissivity, among others. The transmissivity T (m2/sec) is a hydrauli...

  13. 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.

  14. 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.

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

    PubMed

    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

  16. Kv4.2 is a locus for PKC and ERK/MAPK cross-talk

    PubMed Central

    Schrader, Laura A.; Ren, Yajun; Cheng, Feng; Bui, Dui; Sweatt, J. David; Anderson, Anne E.

    2009-01-01

    Transient outward K+ currents are particularly important for the regulation of membrane excitability of neurons and repolarization of action potentials in cardiac myocytes. These currents are modulated by protein kinase C (PKC) activation, and the K+ channel subunit, Kv4.2, is a major contributor to these currents. Furthermore, the current recorded from Kv4.2 channels expressed in oocytes is reduced by PKC activation. The mechanism underlying PKC regulation of Kv4.2 currents is unknown. In this study, we determined that PKC directly phosphorylates the Kv4.2 channel protein. In vitro phosphorylation of the intracellular amino (N)- and carboxyl (C)-termini of Kv4.2 glutathione S-transferase (GST) fusion protein revealed that the Kv4.2 C-terminal was phosphorylated by PKC, while the N-terminal was not. Amino acid mapping and site-directed mutagenesis revealed that the phosphorylated residues on the Kv4.2 C-terminal were Serine (Ser) 447 and Ser537. A phospho-site specific antibody showed that phosphorylation at the Ser537 site increased in the hippocampus in response to PKC activation. Surface biotinylation experiments revealed that alanine mutation to block phosphorylation at both of the PKC sites increased surface expression compared to wildtype Kv4.2. Electrophysiological recordings of the wildtype and both the alanine and aspartate mutant Kv4.2 channels expressed with KChIP3 revealed no significant difference in the half activation or inactivation voltage of the channel. Interestingly, the Ser537 site lies within a possible extracellular regulated kinase (ERK)/mitogen activated protein kinase (MAPK) recognition (docking) domain in the Kv4.2 C-terminal sequence. We found that phosphorylation of Kv4.2 by PKC enhanced ERK phosphorylation of the channel in vitro. These findings suggest the possibility that Kv4.2 is a locus for PKC and ERK cross-talk. PMID:18795890

  17. 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

  18. 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

  19. 2D-3D registration for brain radiation therapy using a 3D CBCT and a single limited field-of-view 2D kV radiograph

    NASA Astrophysics Data System (ADS)

    Munbodh, R.; Moseley, D. J.

    2014-03-01

    We report results of an intensity-based 2D-3D rigid registration framework for patient positioning and monitoring during brain radiotherapy. We evaluated two intensity-based similarity measures, the Pearson Correlation Coefficient (ICC) and Maximum Likelihood with Gaussian noise (MLG) derived from the statistics of transmission images. A useful image frequency band was identified from the bone-to-no-bone ratio. Validation was performed on gold-standard data consisting of 3D kV CBCT scans and 2D kV radiographs of an anthropomorphic head phantom acquired at 23 different poses with parameter variations along six degrees of freedom. At each pose, a single limited field of view kV radiograph was registered to the reference CBCT. The ground truth was determined from markers affixed to the phantom and visible in the CBCT images. The mean (and standard deviation) of the absolute errors in recovering each of the six transformation parameters along the x, y and z axes for ICC were varphix: 0.08(0.04)°, varphiy: 0.10(0.09)°, varphiz: 0.03(0.03)°, tx: 0.13(0.11) mm, ty: 0.08(0.06) mm and tz: 0.44(0.23) mm. For MLG, the corresponding results were varphix: 0.10(0.04)°, varphiy: 0.10(0.09)°, varphiz: 0.05(0.07)°, tx: 0.11(0.13) mm, ty: 0.05(0.05) mm and tz: 0.44(0.31) mm. It is feasible to accurately estimate all six transformation parameters from a 3D CBCT of the head and a single 2D kV radiograph within an intensity-based registration framework that incorporates the physics of transmission images.

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

    PubMed Central

    Haitin, Yoni; Attali, Bernard

    2008-01-01

    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 α 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. PMID:18218681

  1. 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.

  2. Postsynaptic density-93 clusters Kv1 channels at axon initial segments independently of Caspr2.

    PubMed

    Ogawa, Yasuhiro; Horresh, Ido; Trimmer, James S; Bredt, David S; Peles, Elior; Rasband, Matthew N

    2008-05-28

    Postsynaptic density-93 (PSD-93)/Chapsyn-110 is a PDZ (PSD-95/Discs large/zona occludens-1) domain-containing membrane-associated guanylate kinase (MAGUK) that functions as a scaffold to assemble channels, receptors, and other signaling proteins at cell membranes. PSD-93 is highly enriched at synapses, but mice lacking this protein have no synaptic structural abnormalities, probably because of overlapping expression and redundancy with other MAGUKs. Consequently, the function of PSD-93 is not well understood. Here, we show that PSD-93, but not other MAGUKs, is enriched at the axon initial segment (AIS), where it colocalizes with Kv1.1, Kv1.2, Kv1.4, and Kvbeta2 subunit-containing K(+) channels, Caspr2, and TAG-1 (transient axonal glycoprotein-1). When coexpressed with Kv1 channels in heterologous cells, PSD-93 induces formation of large cell-surface clusters. Knockdown of PSD-93 in cultured hippocampal neurons by RNA interference disrupted Kv1 channel localization at the AIS. Similarly, PSD-93-/- mice failed to cluster Kv1 channels at the AIS of cortical and hippocampal neurons. In contrast, Caspr2, which mediates Kv1 channel clustering at the juxtaparanode, is not required for localization of Kv1 channels at the AIS. These results show PSD-93 mediates AIS accumulation of Kv1 channels independently of Caspr2. PMID:18509034

  3. 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.

  4. Joint HVAC transmission EMF environmental study

    SciTech Connect

    Stormshak, F.; Thompson, J. )

    1992-05-01

    This document describes the rationale, procedures, and results of a carefully controlled study conducted to establish whether chronic exposure of female (ewe) Suffolk lambs to the environment of a 500-kV 60-Hz transmission line would affect various characteristics of growth, endocrine function, and reproductive development. This experiment used identical housing and management schemes for control and line-exposed ewes, thus minimizing these factors as contributors to between-group experimental error. Further, throughout the 10-month duration of this study, changes in electric and magnetic fields, audible noise, and weather conditions were monitored continuously by a computerized system. Such measurements provided the opportunity to identify any relationship between environmental factors and biological responses. Because of reports in the literature that electric and magnetic fields alter concentrations of melatonin in laboratory animals, the primary objective of this study was to ascertain whether a similar effect occurs in lambs exposed to a 500-kV a-c line in a natural setting. In addition, onset of puberty, changes in body weight, wool growth, and behavior were monitored. To determine whether the environment of a 500-kV line caused stress in the study animals, serum levels of cortisol were measured. The study was conducted at Bonneville Power Administration's Ostrander Substation near Estacada, Oregon.

  5. Supplement Analysis for the Transmission System Vegetation Management Program FEIS (DOE/EIS-0285/SA-21)

    SciTech Connect

    Rosales, Michael A.

    2001-08-07

    Vegetation Management along the Noxon-Hot Springs/Taft-Hot Springs 56/3 to 66/7+600 Transmission Line ROW. The line is a 230kV and 500KV Double Circuit Transmission Line having an easement width of 250 feet. The proposed work will be accomplished in the indicated sections of the transmission line corridor. BPA proposes to clear unwanted vegetation in the rights-of-ways and around tower structures that may impede the operation and maintenance of the subject transmission line. All work will be in accordance with the National Electrical Safety Code and BPA standards. BPA plans to conduct vegetation control with the goal of removing tall growing vegetation that is currently or will soon be a hazard to the transmission line. BPA’s overall goal is to have low-growing plant communities along the rights-of-way to control the development of potentially threatening vegetation.

  6. Design and development of a prototype 25 kV, 10 A long pulse Marx modulator for high power klystron

    NASA Astrophysics Data System (ADS)

    Acharya, Mahesh; Shrivastava, Purushottam

    2016-02-01

    Research, design, and development of high average power modulators for the proposed Indian Spallation Neutron Source are in progress at Raja Ramanna Centre for Advanced Technology. With this objective, a prototype of 25 kV, 10 A, 1 ms Marx modulator at repetition rate of 1 Hz has been designed and developed which serves as a proof of principle and technology assessment stage for further development of high repetition rate high voltage high average power modulators. Insulated Gate Bipolar Transistor (IGBT) based modules of 2.8 kV switching capability have been used as main modules. The modulator had 8.2% droop in output voltage pulse without any droop compensation circuit. A droop compensation involving 15 corrector modules has been used to reduce the droop up to 1%. We have used IGBT based 250 V switches to realize the corrector module. A microcontroller based control unit was designed and developed for triggering the main and corrector modules. With this control unit, programmable output pulse has been achieved. Electrical isolation between high voltage circuits and control circuit has been achieved by the use of fiber optic based control signal transmission. Output pulses of 1 ms pulse width, 800 ns rise time, and 5 μs fall time have been achieved. The modulator has advantages of modular design, adjustable pulse width, adjustable rise time, and fall time.

  7. Vasorelaxant effects of novel Kv7.4 channel enhancers ML213 and NS15370

    PubMed Central

    Jepps, T A; Bentzen, B H; Stott, J B; Povstyan, O V; Sivaloganathan, K; Dalby-Brown, W; Greenwood, I A

    2014-01-01

    Background and Purpose The KCNQ-encoded voltage-gated potassium channel family (Kv7.1-Kv7.5) are established regulators of smooth muscle contractility, where Kv7.4 and Kv7.5 predominate. Various Kv7.2–7.5 channel enhancers have been developed that have been shown to cause a vasorelaxation in both rodent and human blood vessels. Recently, two novel Kv7 channel enhancers have been identified, ML213 and NS15370, that show increased potency, particularly on Kv7.4 channels. The aim of this study was to characterize the effects of these novel enhancers in different rat blood vessels and compare them with Kv7 enhancers (S-1, BMS204352, retigabine) described previously. We also sought to determine the binding sites of the new Kv7 enhancers. Key Results Both ML213 and NS15370 relaxed segments of rat thoracic aorta, renal artery and mesenteric artery in a concentration-dependent manner. In the mesenteric artery ML213 and NS15370 displayed EC50s that were far lower than other Kv7 enhancers tested. Current-clamp experiments revealed that both novel enhancers, at low concentrations, caused significant hyperpolarization in mesenteric artery smooth muscle cells. In addition, we determined that the stimulatory effect of these enhancers relied on a tryptophan residue located in the S5 domain, which is the same binding site for the other Kv7 enhancers tested in this study. Conclusions and Implications This study has identified and characterized ML213 and NS15370 as potent vasorelaxants in different blood vessels, thereby highlighting these new compounds as potential therapeutics for various smooth muscle disorders. PMID:24909207

  8. The Tetramerization Domain Potentiates Kv4 Channel Function by Suppressing Closed-State Inactivation

    PubMed Central

    Tang, Yi-Quan; Zhou, Jing-Heng; Yang, Fan; Zheng, Jie; Wang, KeWei

    2014-01-01

    A-type Kv4 potassium channels undergo a conformational change toward a nonconductive state at negative membrane potentials, a dynamic process known as pre-open closed states or closed-state inactivation (CSI). CSI causes inhibition of channel activity without the prerequisite of channel opening, thus providing a dynamic regulation of neuronal excitability, dendritic signal integration, and synaptic plasticity at resting. However, the structural determinants underlying Kv4 CSI remain largely unknown. We recently showed that the auxiliary KChIP4a subunit contains an N-terminal Kv4 inhibitory domain (KID) that directly interacts with Kv4.3 channels to enhance CSI. In this study, we utilized the KChIP4a KID to probe key structural elements underlying Kv4 CSI. Using fluorescence resonance energy transfer two-hybrid mapping and bimolecular fluorescence complementation-based screening combined with electrophysiology, we identified the intracellular tetramerization (T1) domain that functions to suppress CSI and serves as a receptor for the binding of KID. Disrupting the Kv4.3 T1-T1 interaction interface by mutating C110A within the C3H1 motif of T1 domain facilitated CSI and ablated the KID-mediated enhancement of CSI. Furthermore, replacing the Kv4.3 T1 domain with the T1 domain from Kv1.4 (without the C3H1 motif) or Kv2.1 (with the C3H1 motif) resulted in channels functioning with enhanced or suppressed CSI, respectively. Taken together, our findings reveal a novel (to our knowledge) role of the T1 domain in suppressing Kv4 CSI, and that KChIP4a KID directly interacts with the T1 domain to facilitate Kv4.3 CSI, thus leading to inhibition of channel function. PMID:25185545

  9. ADAM22, A KV1 CHANNEL INTERACTING PROTEIN, RECRUITS MAGUKS TO JUXTAPARANODES OF MYELINATED AXONS

    PubMed Central

    Ogawa, Yasuhiro; Oses-Prieto, Juan; Kim, Moon Young; Horresh, Ido; Peles, Elior; Burlingame, Alma L.; Trimmer, James S.; Meijer, Dies; Rasband, Matthew N.

    2009-01-01

    Clustered Kv1 K+ channels regulate neuronal excitability at juxtaparanodes of myelinated axons, axon initial segments (AIS), and cerebellar basket cell terminals (BCTs). These channels are part of a larger protein complex that includes cell adhesion molecules and scaffolding proteins. To identify proteins that regulate assembly, clustering, and/or maintenance of axonal Kv1 channel protein complexes, we immunoprecipitated Kv1.2 α subunits, then used mass-spectrometry to identify interacting proteins. We found that ADAM22 (A Disintegrin And Metalloproteinase 22) is a component of the Kv1 channel complex, and that ADAM22 co-immunoprecipitates Kv1.2 and the MAGUKs PSD-93 and PSD-95. When co-expressed with MAGUKs in heterologous cells, ADAM22 and Kv1 channels are recruited into membrane surface clusters. However, co-expression of Kv1.2 with ADAM22 and MAGUKs does not alter channel properties. Among all the known Kv1 channel interacting proteins, only ADAM22 is found at every site where Kv1 channels are clustered. Analysis of Caspr-null mice showed that like other previously described juxtaparanodal proteins, disruption of the paranodal junction resulted in redistribution of ADAM22 into paranodal zones. Analysis of Caspr2-, PSD-93-, PSD-95-, and double PSD-93/PSD-95-null mice showed ADAM22 clustering at BCTs requires PSD-95, but ADAM22 clustering at juxtaparanodes requires neither PSD-93 nor PSD-95. In direct contrast, analysis of ADAM22-null mice demonstrated juxtaparanodal clustering of PSD-93 and PSD-95 requires ADAM22, whereas Kv1.2 and Caspr2 clustering is normal in ADAM22-null mice. Thus, ADAM22 is an axonal component of the Kv1 K+ channel complex that recruits MAGUKs to juxtaparanodes. PMID:20089912

  10. Environmental assessment: Coolidge-Saguaro 115-kV rehabilitation, Pinal County, Arizona

    SciTech Connect

    Not Available

    1982-09-01

    This Environmental Assessment (EA) presents an analysis of the environmental impacts of the proposed rehabilitation of 29.6 miles of the Coolidge-Saguaro 115-kV transmission line. The project area is in Pinal County, Arizona. The proposal involves reconductoring the line with larger conductor, replacement of deteriorated structures, and replacement of damaged insulators. The proposed action is being considered in order to increase the safety and reliability of this line. The alternative of no action is also addressed in this EA. The proposed action would have insignificant impacts on wildlife, vegetation or other natural resources. There would be no impacts on floodplains or wetlands. The major impact would be on agricultural crops but much of this can be minimized by the timing of construction. There are no conflicts with county or local planning projects. No cultural resources will be affected by the proposed action. The no action alternative would not correct the potential safety hazard or reliability problems of the existing line.

  11. Experimental Studies on Cryogenic System for 22.9 KV Hts Cable Sytem

    NASA Astrophysics Data System (ADS)

    Sohn, S. H.; Lim, J. H.; Yang, H. S.; Kim, D. L.; Ryoo, H. S.; Kim, C. D.; Kim, D. H.; Lee, S. K.; Hwang, S. D.

    2008-03-01

    In terms of high transmission capacity with lower voltage, a high temperature superconducting (HTS) cable system is a very attractive challenge for utilities. However, the concomitant cryogenic system for the HTS cable system is one of the tantalizing problems in the operation. The reliability and maintainability of cryogenic system are the key issues to apply it to the real electric power grid. Korea Electric Power Corporation (KEPCO) is making an attempt to verify the applicability of the HTS cable system to improve the efficiency of electric power industry. Since May 2006, a 22.9-kV, 50-MVA, 3-phase, 100-m class HTS cable system with an open cooling system has been operated at the KEPCO Gochang test yard. Concurrently, another HTS cable verification test with the same electrical specification and an hybrid cooling system has been carried out by LS Cable (LSC) Ltd in close proximity to the KEPCO's HTS cable system within Gochang test yard. KEPCO conducts the operation of the open cooling system, and is evaluating the hybrid system of LSC with respect to facility performance and usability. This paper compares the cryogenic performance of both HTS cable systems and discusses cooling test results such as step response.

  12. SAP97 increases Kv1.5 currents through an indirect N-terminal mechanism.

    PubMed

    Eldstrom, Jodene; Choi, Woo Sung; Steele, David F; Fedida, David

    2003-07-17

    The functional interaction of the voltage-gated potassium channel hKv1.5 with the PDZ domain containing protein SAP97 has been investigated. In marked contrast with the known dependence of SAP97-induced Kv1 potassium current down-regulation on the channel C-termini, SAP97 increased hKv1.5 current through an indirect interaction with the Kv1.5 N-terminus. Deletion of the Kv1.5 N-terminus eliminated the SAP97-mediated increase in potassium currents whereas deletion of the channel's C-terminal PDZ binding motif had no effect. In contrast with other Kv1-SAP97 interactions, no physical interaction could be detected in vivo or in vitro between the two proteins. The proteins did not co-localize in cardiac myocytes nor did they co-immunoprecipitate from transfected HEK cells. Yeast two-hybrid experiments also failed to detect any interaction between the two proteins, but in one experiment of six, Kv1.5 co-immunoprecipitated very inefficiently with SAP97 from rat ventricular myocytes. Thus, we conclude that the influence of SAP97 on Kv1.5 potassium current levels is dependent upon a novel regulatory mechanism. PMID:12860415

  13. Developmental expression of Kv1 voltage-gated potassium channels in the avian hypothalamus.

    PubMed

    Doczi, Megan A; Vitzthum, Carl M; Forehand, Cynthia J

    2016-03-11

    Specialized hypothalamic neurons integrate the homeostatic balance between food intake and energy expenditure, processes that may become dysregulated during the development of diabetes, obesity, and other metabolic disorders. Shaker family voltage-gated potassium channels (Kv1) contribute to the maintenance of resting membrane potential, action potential characteristics, and neurotransmitter release in many populations of neurons, although hypothalamic Kv1 channel expression has been largely unexplored. Whole-cell patch clamp recordings from avian hypothalamic brain slices demonstrate a developmental shift in the electrophysiological properties of avian arcuate nucleus neurons, identifying an increase in outward ionic current that corresponds with action potential maturation. Additionally, RT-PCR experiments identified the early expression of Kv1.2, Kv1.3, and Kv1.5 mRNA in the embryonic avian hypothalamus, suggesting that these channels may underlie the electrophysiological changes observed in these neurons. Real-time quantitative PCR analysis on intact microdissections of embryonic hypothalamic tissue revealed a concomitant increase in Kv1.2 and Kv1.5 gene expression at key electrophysiological time points during development. This study is the first to demonstrate hypothalamic mRNA expression of Kv1 channels in developing avian embryos and may suggest a role for voltage-gated ion channel regulation in the physiological patterning of embryonic hypothalamic circuits governing energy homeostasis.

  14. 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…

  15. Remodeling of Kv4.3 potassium channel gene expression under the control of sex hormones.

    PubMed

    Song, M; Helguera, G; Eghbali, M; Zhu, N; Zarei, M M; Olcese, R; Toro, L; Stefani, E

    2001-08-24

    Kv4.3 channels are important molecular components of transient K(+) currents (Ito currents) in brain and heart. They are involved in setting the frequency of neuronal firing and heart pacing. Altered Kv4.3 channel expression has been demonstrated under pathological conditions like heart failure indicating their critical role in heart function. Thyroid hormone studies suggest that their expression in the heart may be hormonally regulated. To explore the possibility that sex hormones control Kv4.3 expression, we investigated whether its expression changes in the pregnant uterus. This organ represents a unique model to study Ito currents, because it possesses this type of K(+) current and undergoes dramatic changes in function and excitability during pregnancy. We cloned Kv4.3 channel from myometrium and found that its protein and transcript expression is greatly diminished during pregnancy. Experiments in ovariectomized rats demonstrate that estrogen is one mechanism responsible for the dramatic reduction in Kv4.3 expression and function prior to parturition. Furthermore, the reduction of plasma membrane Kv4.3 protein is accompanied by a perinuclear localization suggesting that cell trafficking is also controlled by sex hormones. Thus, estrogen remodels the expression of Kv4.3 in myometrium by directly diminishing its transcription and, indirectly, by altering Kv4.3 delivery to the plasma membrane. PMID:11427525

  16. Porphyrin derivatives as potent and selective blockers of neuronal Kv1 channels.

    PubMed

    Daly, D; Al-Sabi, A; Kinsella, G K; Nolan, K; Dolly, J O

    2015-01-21

    Selective inhibitors of voltage-activated K(+) channels are needed for the treatment of multiple sclerosis. In this work it was discovered that porphyrins bearing 2-4 carbon alkyl ammonium side chains predominantly blocked the Kv1.1 current whilst Kv1.2 was susceptible to a porphyrin bearing polyamine side chains.

  17. Application of intelligent optimal kV scanning technology (CARE kV) in dual-source computed tomography (DSCT) coronary angiography.

    PubMed

    Zhang, Jun; Kang, Shaolei; Han, Dan; Xie, Xiaojie; Deng, Yaming

    2015-01-01

    This study aims to evaluate the applications and values of dual-source computed tomography (DSCT) intelligent optimal kV scanning technology (CARE kV) in coronary CT angiography (CCTA). 150 patients with normal body mass index were performed DSCT coronary angiography, then randomly divided into the "Semi", 120,100 and 80 kV Group, and the 2 "on" groups, with 30 patients in each group. The first 5 groups used the reference voltage as 120 kV, and the reference current as 400 mAs, while the other group used the reference voltage as 100 kV, and the reference current as 400 mAs. The image quality, average CT value, image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and radiation dose were comparatively analyzed among the 5 groups. The image quality scores of the five groups showed no significant difference (P > 0.05); the average CT values and image noises had significance (P < 0.05), while SNR and CNR showed no significant difference (P > 0.05). The 80 kV group showed the biggest noise, with the CT value as 700 HU, while the radiation dose was the lowest, followed by the on group. As for the patients with normal body mass index (BMI), CARE kV-"on" could obtain high-quality images and lower radiation dose for CCTA, while the operation was simple and convenient.

  18. 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

  19. Kv7.2 regulates the function of peripheral sensory neurons.

    PubMed

    King, Chih H; Lancaster, Eric; Salomon, Daniela; Peles, Elior; Scherer, Steven S

    2014-10-01

    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

  20. 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

  1. Clean fog flashover tests on 138-kV nonceramic line post insulators before and after artificial aging

    SciTech Connect

    Schneider, H.M.; Guidi, W.W.; Howes, D.R. . High Voltage Transmission Research Center)

    1992-10-01

    This report describes research conducted to determine the contamination performance of [sup 138] kV transmission line insulators utilized by Florida Power and Light Co. Although test results for both ceramic and nonceramic insulators are reported, emphasis is placed on the performance of nonceramic line posts before and after artificial aging. Since it was not possible to obtain nonceramic insulators that were aged in the same environment and for the same amount of time, there was a need to develop an accelerated aging chamber in order to age these insulators artificially. The aging cycle for these tests is designed to represent the severe coastal climate of Florida. Aging is judged by physical observations, leakage current analysis during aging, analytical material measurements and contamination flashover voltage. Flashover performance is evaluated as a function of contamination severity as determined by equivalent salt deposit density (ESDD). Radio interference (RI), television interference (TVI) and audible noise (AN), during contamination flashover tests, are also described.

  2. Clean fog flashover tests on 138-kV nonceramic line post insulators before and after artificial aging. Final report

    SciTech Connect

    Schneider, H.M.; Guidi, W.W.; Howes, D.R.

    1992-10-01

    This report describes research conducted to determine the contamination performance of {sup 138} kV transmission line insulators utilized by Florida Power and Light Co. Although test results for both ceramic and nonceramic insulators are reported, emphasis is placed on the performance of nonceramic line posts before and after artificial aging. Since it was not possible to obtain nonceramic insulators that were aged in the same environment and for the same amount of time, there was a need to develop an accelerated aging chamber in order to age these insulators artificially. The aging cycle for these tests is designed to represent the severe coastal climate of Florida. Aging is judged by physical observations, leakage current analysis during aging, analytical material measurements and contamination flashover voltage. Flashover performance is evaluated as a function of contamination severity as determined by equivalent salt deposit density (ESDD). Radio interference (RI), television interference (TVI) and audible noise (AN), during contamination flashover tests, are also described.

  3. Infrared Applications In Transmission System Surveys

    NASA Astrophysics Data System (ADS)

    Nelson, Guy; Fernandez, Joe

    1988-01-01

    Five California Utilities participated in an electric power transmission and distribution system survey in the late fall of 1987. The survey consisted of visual and Infrared (IR) inspection of 12.5-kV to 230-kV AC transmission lines and equipment. This paper summarizes the results of the survey, including a cost/benefit analysis. The participating utilities, under Western Area Power Administration's sponsorship, were the City of Lodi, City of Roseville, Plumas-Sierra Rural Electric Cooperative, Sacramento Municipal Utility District, and Sierra Pacific Power Company. Three hundred miles of line and thirty substations were inspected using a helicopter and a high resolution infrared camera with visual recording capabilities. The transmission and distribution system covered a broad range of terrain; valleys, foothills, and mountains. All five utilities recognized the value of the IR inspection. The procedure gave the maintenance staff advanced notice of problem areas such as (1) loose connections on switches, (2) unbalanced lines, (3) poor splices, and (4) capacitor and transformer bank malfunction. In addition, the staff saw its potential in environmental and safety applications. The initial data shows an increased capacity carrying and reliability providing capability of about 50 KW per 100 transmission line miles. This capability increase results in a B/C ratio of about three. Other applications in transmission system surveys are worthy of study. These applications include power theft and vandalism. Also, the Utility can use technology as an effective public relations tool with customers by providing services such as roof and building envelope inspections.

  4. Phosphatidic acid modulation of Kv channel voltage sensor function.

    PubMed

    Hite, Richard K; Butterwick, Joel A; MacKinnon, Roderick

    2014-01-01

    Membrane phospholipids can function as potent regulators of ion channel function. This study uncovers and investigates the effect of phosphatidic acid on Kv channel gating. Using the method of reconstitution into planar lipid bilayers, in which protein and lipid components are defined and controlled, we characterize two effects of phosphatidic acid. The first is a non-specific electrostatic influence on activation mediated by electric charge density on the extracellular and intracellular membrane surfaces. The second is specific to the presence of a primary phosphate group, acts only through the intracellular membrane leaflet and depends on the presence of a particular arginine residue in the voltage sensor. Intracellular phosphatidic acid accounts for a nearly 50 mV shift in the midpoint of the activation curve in a direction consistent with stabilization of the voltage sensor's closed conformation. These findings support a novel mechanism of voltage sensor regulation by the signaling lipid phosphatidic acid. PMID:25285449

  5. Transmissible amyloid.

    PubMed

    Tjernberg, L O; Rising, A; Johansson, J; Jaudzems, K; Westermark, P

    2016-08-01

    There are around 30 human diseases associated with protein misfolding and amyloid formation, each one caused by a certain protein or peptide. Many of these diseases are lethal and together they pose an enormous burden to society. The prion protein has attracted particular interest as being shown to be the pathogenic agent in transmissible diseases such as kuru, Creutzfeldt-Jakob disease and bovine spongiform encephalopathy. Whether similar transmission could occur also in other amyloidoses such as Alzheimer's disease, Parkinson's disease and serum amyloid A amyloidosis is a matter of intense research and debate. Furthermore, it has been suggested that novel biomaterials such as artificial spider silk are potentially amyloidogenic. Here, we provide a brief introduction to amyloid, prions and other proteins involved in amyloid disease and review recent evidence for their potential transmission. We discuss the similarities and differences between amyloid and silk, as well as the potential hazards associated with protein-based biomaterials. PMID:27002185

  6. Prion transmission

    PubMed Central

    Maddison, Ben C

    2010-01-01

    Prion diseases range from being highly infectious, for example scrapie and CWD, which show facile transmission between susceptible individuals, to showing negligible horizontal transmission, such as BSE and CJD, which are spread via food or iatrogenically, respectively. Scrapie and CWD display considerable in vivo dissemination, with PrPSc and infectivity being found in a range of peripheral tissues. This in vivo dissemination appears to facilitate the recently reported excretion of prion through multiple routes such as from skin, feces, urine, milk, nasal secretions, saliva and placenta. Furthermore, excreted scrapie and CWD agent is detected within environmental samples such as water and on the surfaces of inanimate objects. The cycle of “uptake of prion from the environment—widespread in vivo prion dissemination—prion excretion—prion persistence in the environment” is likely to explain the facile transmission and maintenance of these diseases within wild and farmed populations over many years. PMID:20948292

  7. 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

  8. 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

  9. Modeling the binding modes of Kv1.5 potassium channel and blockers.

    PubMed

    Yang, Qian; Du, Lupei; Wang, Xiaojian; Li, Minyong; You, Qidong

    2008-09-01

    The ultra-rapid delayed rectifier potassium current (I(Kur)), encoded by Kv1.5 gene, is the critical determinant of Phase I repolarization of action potential duration (APD). The evidences that Kv1.5 gene expresses more extensively in human atrial myocytes than in ventricle and the I(Kur) currents has not been recorded in the human ventricle, suggest Kv1.5 potassium channel as a selective target for the treatment of atrial fibrillation (AF). Recent mutagenesis studies have provided us some evidences that are useful in designing Kv1.5 blockers. In order to further evaluate these molecular biological information, the homology model of Kv1.5 potassium channel was established based on the Kv1.2 crystal structure (PDB entry: 2A79) using MODELLER 9v2 program. After the molecular dynamics refinement, the optimized homology model was assessed as a reliable structure by PROCHECK, ERRAT, WHAT-IF, PROSA2003 and DOPE graph. The results of molecular docking studies on different Kv1.5 inhibitors are in agreement with the published mutagenesis data. Based on the docking conformations, a pharmacophore model was developed by HipHop algorithm in order to probe the common features of blockers. By analyzing the results, active site architecture, certain key residues and pharmacophore common-features that are responsible for substrate specificity were identified on the Kv1.5 potassium channel, which would be very helpful in understanding the blockade mechanism of Kv1.5 potassium channel and providing insights into rational design of novel Kv1.5 blockers. PMID:18485768

  10. Modeling the binding modes of Kv1.5 potassium channel and blockers.

    PubMed

    Yang, Qian; Du, Lupei; Wang, Xiaojian; Li, Minyong; You, Qidong

    2008-09-01

    The ultra-rapid delayed rectifier potassium current (I(Kur)), encoded by Kv1.5 gene, is the critical determinant of Phase I repolarization of action potential duration (APD). The evidences that Kv1.5 gene expresses more extensively in human atrial myocytes than in ventricle and the I(Kur) currents has not been recorded in the human ventricle, suggest Kv1.5 potassium channel as a selective target for the treatment of atrial fibrillation (AF). Recent mutagenesis studies have provided us some evidences that are useful in designing Kv1.5 blockers. In order to further evaluate these molecular biological information, the homology model of Kv1.5 potassium channel was established based on the Kv1.2 crystal structure (PDB entry: 2A79) using MODELLER 9v2 program. After the molecular dynamics refinement, the optimized homology model was assessed as a reliable structure by PROCHECK, ERRAT, WHAT-IF, PROSA2003 and DOPE graph. The results of molecular docking studies on different Kv1.5 inhibitors are in agreement with the published mutagenesis data. Based on the docking conformations, a pharmacophore model was developed by HipHop algorithm in order to probe the common features of blockers. By analyzing the results, active site architecture, certain key residues and pharmacophore common-features that are responsible for substrate specificity were identified on the Kv1.5 potassium channel, which would be very helpful in understanding the blockade mechanism of Kv1.5 potassium channel and providing insights into rational design of novel Kv1.5 blockers.

  11. Requisite Role of Kv1.5 Channels in Coronary Metabolic Dilation

    PubMed Central

    Bardakjian, Raffi; Kolz, Christopher; Enrick, Molly; Hakobyan, Tatevik; Kmetz, John; Bratz, Ian; Luli, Jordan; Nagane, Masaki; Khan, Nadeem; Hou, Huagang; Kuppusamy, Periannan; Graham, Jacqueline; Fu, Frances Kwan; Janota, Danielle; Oyewumi, Moses O.; Logan, Suzanna; Lindner, Jonathan R.; Chilian, William M.

    2016-01-01

    Rationale In the working heart coronary blood flow is linked to the production of metabolites, which modulate tone of smooth muscle in a redox-dependent manner. Voltage-gated potassium channels, which play a role in controlling membrane potential in vascular smooth muscle, have certain members that are redox sensitive. Objective To determine the role of redox-sensitive Kv1.5 channels in coronary metabolic flow regulation. Methods and Results In mice (wild type [WT], Kv1.5 null [Kv1.5−/−], and Kv1.5−/− and WT with inducible, smooth muscle specific expression of Kv1.5 channels) we measured mean arterial pressure (MAP), myocardial blood flow (MBF), myocardial tissue pO2, and ejection fraction (EF) before and after inducing cardiac stress with norepinephrine (NE). Cardiac work (CW) was estimated as the product of MAP and heart rate. Isolated arteries were studied to establish if genetic alterations modified vascular reactivity. Despite higher levels of CW in the Kv1.5−/− (versus WT at baseline and all doses of NE), MBF was lower in Kv1.5−/− than in WT. At high levels of CW, tissue pO2 dropped significantly along with EF. Expression of Kv1.5 channels in smooth muscle in the null background rescued this phenotype of impaired metabolic dilation. In isolated vessels from Kv1.5−/− mice, relaxation to H2O2 was impaired, but responses to adenosine and acetylcholine were normal compared to WT. Conclusions Kv1.5 channels in vascular smooth muscle play a critical role in coupling myocardial blood flow to cardiac metabolism. Absence of these channels disassociates metabolism from flow resulting in cardiac pump dysfunction and tissue hypoxia. PMID:26224794

  12. The role of Kif5B in axonal localization of Kv1 K(+) channels.

    PubMed

    Rivera, Jacqueline; Chu, Po-Ju; Lewis, Tommy L; Arnold, Don B

    2007-01-01

    Here we present evidence that the kinesin, Kif5B, is involved in the transportation and axonal targeting of Kv1 channels. We show that a dominant negative variant of Kif5B specifically blocks localization to the axon of expressed, tagged versions of Kv1.3 in cultured cortical slices. In addition, the dominant negative variant of Kif5B blocks axonal localization of endogenous Kv1.1, Kv1.2, and Kv1.4 in cortical neurons in dissociated cultures. We also found evidence that Kif5B interacts with Kv1 channels. Endogenous Kv1.2 colocalized with Kif5B in cortical neurons and coimmunoprecipitated with Kif5B from brain lysate. The T1 domain of Shaker K(+) channels has been shown to play a critical role in targeting the channel to the axon. We have three pieces of evidence to suggest that the T1 domain also mediates interaction between Kv1 channels and Kif5B: Addition of the T1 domain to a heterologous protein, TfR, is sufficient to cause the resulting fusion protein, TfRT1, to colocalize with Kif5B. Also, the T1 domain is necessary for interaction of Kv1.3 with Kif5B in a coimmunoprecipitation assay. Finally, dominant negative variants of Kif5B block axonal targeting of TfRT1, but have no effect on dendritic localization of TfR. Together these data suggest a model where Kif5B interacts with Kv1 channels either directly or indirectly via the T1 domain, causing the channels to be transported to axons. PMID:17241275

  13. Rotorcraft transmissions

    NASA Technical Reports Server (NTRS)

    Coy, John J.

    1990-01-01

    Highlighted here is that portion of the Lewis Research Center's helicopter propulsion systems program that deals with drive train technology and the related mechanical components. The major goals of the program are to increase life, reliability, and maintainability, to reduce weight, noise, and vibration, and to maintain the relatively high mechanical efficiency of the gear train. The current activity emphasizes noise reduction technology and analytical code development, followed by experimental verification. Selected significant advances in technology for transmissions are reviewed, including advanced configurations and new analytical tools. Finally, the plan for transmission research in the future is presented.

  14. 77 FR 58096 - Georgia Transmission Corporation: Notice of Intent To Prepare an Environmental Assessment and To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-19

    ... of 230 kilovolt (kV) transmission line in portions of Atkinson, Berrien, Clinch, Coffee, and Lanier...; and at the following repositories: Douglas/Coffee County Public Library, South Madison Ave., Douglas... on the northwest side of the City of Douglas in Coffee County, Georgia, to an existing...

  15. STEM imaging of 47-pm-separated atomic columns by a spherical aberration-corrected electron microscope with a 300-kV cold field emission gun.

    PubMed

    Sawada, Hidetaka; Tanishiro, Yasumasa; Ohashi, Nobuhiro; Tomita, Takeshi; Hosokawa, Fumio; Kaneyama, Toshikatsu; Kondo, Yukihito; Takayanagi, Kunio

    2009-12-01

    A spherical aberration-corrected electron microscope has been developed recently, which is equipped with a 300-kV cold field emission gun and an objective lens of a small chromatic aberration coefficient. A dumbbell image of 47 pm spacing, corresponding to a pair of atomic columns of germanium aligned along the [114] direction, is resolved in high-angle annular dark field (HAADF) scanning transmission electron microscopy (STEM) with a 0.4-eV energy spread of the electron beam. The observed image was compared with a simulated image obtained by dynamical calculation.

  16. Supplement Analysis for the Transmission System Vegetation Management Program FEIS (DOE/EIS-0285/SA-25) - Ostrander-Pearl Transmission Line

    SciTech Connect

    Stratton, Elaine S.

    2001-09-05

    Vegetation Management along selected ROW sections of the Ostrander-Pearl transmission line. The ROWs include sections of the Ostrander-Pearl 500 kV line; the Ostrander-McLoughlin 500 kV line; the Big Eddy-Chemawa 230 kV line and the Big Eddy-McLoughlin 230 kV line. BPA proposes to clear unwanted vegetation in the rights-of-way and around tower structures that may impede the operation and maintenance of the subject transmission lines. The project also includes clearing approximately 3 miles of access road and cutting of some danger trees. All work will be in accordance with the National Electrical Safety Code and BPA Standards. BPA plans to conduct vegetation control with the goal of removing tall-growing vegetation that is currently or will soon be a hazard to the transmission lines and to promote low-growing plant communities in the right-of-way and to clear vegetation from new rights-of-way corridors.

  17. 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

  18. 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

  19. 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.

  20. 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

  1. 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…

  2. 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

  3. Supplement Analysis for the Transmission System Vegetation Management Program FEIS (DOE/EIS-0285/SA-114) (Chehalis-Raymond #1, ADNO 8114)

    SciTech Connect

    Shurtliff, Aaron

    2002-12-05

    Vegetation Management for portion of the Chehalis-Raymond #1 115 kV transmission line. BPA proposes to clear targeted vegetation within the Right-of-Ways along access roads and around towers that may impede the operation and maintenance of the subject transmission lines. See Section 1.4 of the attached checklists for a complete description of the proposed action.

  4. Supplement Analysis for the Transmission System Vegetation Management Program FEIS (DOE/EIS-0285/SA-129 Ashe-Marion #2 [Mile 150-157])

    SciTech Connect

    Jahn, Oden W.

    2003-03-07

    Vegetation Management for the Ashe-Marion #2 500 kV transmission line from structure 150/2 through structure 157/7. Bonneville Power Administration proposes to remove unwanted vegetation along the right-of-way, access roads and around tower structures along the subject transmission line corridors.

  5. 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

  6. Functional KV10.1 Channels Localize to the Inner Nuclear Membrane

    PubMed Central

    Chen, Ye; Sánchez, Araceli; Rubio, María E.; Kohl, Tobias; Pardo, Luis A.; Stühmer, Walter

    2011-01-01

    Ectopically expressed human KV10.1 channels are relevant players in tumor biology. However, their function as ion channels at the plasma membrane does not totally explain their crucial role in tumors. Both in native and heterologous systems, it has been observed that a majority of KV10.1 channels remain at intracellular locations. In this study we investigated the localization and possible roles of perinuclear KV10.1. We show that KV10.1 is expressed at the inner nuclear membrane in both human and rat models; it co-purifies with established inner nuclear membrane markers, shows resistance to detergent extraction and restricted mobility, all of them typical features of proteins at the inner nuclear membrane. KV10.1 channels at the inner nuclear membrane are not all transported directly from the ER but rather have been exposed to the extracellular milieu. Patch clamp experiments on nuclei devoid of external nuclear membrane reveal the existence of channel activity compatible with KV10.1. We hypothesize that KV10.1 channels at the nuclear envelope might participate in the homeostasis of nuclear K+, or indirectly interact with heterochromatin, both factors known to affect gene expression. PMID:21559285

  7. Vascular KCNQ (Kv7) potassium channels as common signaling intermediates and therapeutic targets in cerebral vasospasm.

    PubMed

    Mani, Bharath K; O'Dowd, James; Kumar, Lalit; Brueggemann, Lioubov I; Ross, Masey; Byron, Kenneth L

    2013-01-01

    Cerebral vasospasm after subarachnoid hemorrhage (SAH) is characterized by prolonged severe constriction of the basilar artery, which often leads to ischemic brain damage. Locally elevated concentrations of spasmogenic substances induce persistent depolarization of myocytes in the basilar artery, leading to continuous influx of calcium (Ca) through voltage-sensitive Ca channels and myocyte contraction. Potassium (K) channel openers may have therapeutic utility to oppose membrane depolarization, dilate the arteries, and reduce ischemia. Here, we examined the involvement of vascular Kv7 K channels in the pathogenesis of cerebral vasospasm and tested whether Kv7 channel openers are effective therapeutic agents in a rat model of SAH. Patch-clamp experiments revealed that 3 different spasmogens (serotonin, endothelin, and vasopressin) suppressed Kv7 currents and depolarized freshly isolated rat basilar artery myocytes. These effects were significantly reduced in the presence of a Kv7 channel opener, retigabine. Retigabine (10 μM) also significantly blocked L-type Ca channels, reducing peak inward currents by >50%. In the presence of a selective Kv7 channel blocker, XE991, the spasmogens did not produce additive constriction responses measured using pressure myography. Kv7 channel openers (retigabine or celecoxib) significantly attenuated basilar artery spasm in rats with experimentally induced SAH. In conclusion, we identify Kv7 channels as common targets of vasoconstrictor spasmogens and as candidates for therapeutic intervention for cerebral vasospasm.

  8. Vascular KCNQ (Kv7) potassium channels as common signaling intermediates and therapeutic targets in cerebral vasospasm

    PubMed Central

    Mani, Bharath K.; O'Dowd, James; Kumar, Lalit; Brueggemann, Lioubov I.; Ross, Masey; Byron, Kenneth L.

    2012-01-01

    Cerebral vasospasm following subarachnoid hemorrhage (SAH) is characterized by prolonged severe constriction of the basilar artery, which often leads to ischemic brain damage. Locally elevated concentrations of spasmogenic substances induce persistent depolarization of myocytes in the basilar artery, leading to continuous influx of calcium (Ca2+) through voltage-sensitive Ca2+ channels and myocyte contraction. Potassium (K+) channel openers may have therapeutic utility to oppose membrane depolarization, dilate the arteries, and reduce ischemia. Here, we examined the involvement of vascular Kv7 K+ channels in the pathogenesis of cerebral vasospasm and tested whether Kv7 channel openers are effective therapeutic agents in a rat model of SAH. Patch-clamp experiments revealed that three different spasmogens (serotonin, endothelin and vasopressin) suppressed Kv7 currents and depolarized freshly isolated rat basilar artery myocytes. These effects were significantly reduced in the presence of a Kv7 channel opener, retigabine. Retigabine (10 μmol/L) also significantly blocked L-type Ca2+ channels, reducing peak inward currents by >50%. In the presence of a selective Kv7 channel blocker, XE991, the spasmogens did not produce additive constriction responses measured using pressure myography. Kv7 channel openers (retigabine or celecoxib) significantly attenuated basilar artery spasm in rats with experimentally-induced SAH. In conclusion, we identify Kv7 channels as common targets of vasoconstrictor spasmogens and as candidates for therapeutic intervention for cerebral vasospasm. PMID:23107868

  9. KCNE1 Constrains the Voltage Sensor of Kv7.1 K+ Channels

    PubMed Central

    Yisharel, Ilanit; Malka, Eti; Schottelndreier, Hella; Peretz, Asher; Paas, Yoav; Attali, Bernard

    2008-01-01

    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. PMID:18398469

  10. 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.

  11. A role for DPPX modulating external TEA sensitivity of Kv4 channels.

    PubMed

    Colinas, Olaia; Pérez-Carretero, Francisco D; López-López, José R; Pérez-García, M Teresa

    2008-05-01

    Shal-type (Kv4) channels are expressed in a large variety of tissues, where they contribute to transient voltage-dependent K+ currents. Kv4 are the molecular correlate of the A-type current of neurons (I(SA)), the fast component of I(TO) current in the heart, and also of the oxygen-sensitive K+ current (K(O2)) in rabbit carotid body (CB) chemoreceptor cells. The enormous degree of variability in the physiological properties of Kv4-mediated currents can be attributable to the complexity of their regulation together with the large number of ancillary subunits and scaffolding proteins that associate with Kv4 proteins to modify their trafficking and their kinetic properties. Among those, KChIPs and DPPX proteins have been demonstrated to be integral components of I(SA) and I(TO) currents, as their coexpression with Kv4 subunits recapitulates the kinetics of native currents. Here, we explore the presence and functional contribution of DPPX to K(O2) currents in rabbit CB chemoreceptor cells by using DPPX functional knockdown with siRNA. Additionally, we investigate if the presence of DPPX endows Kv4 channels with new pharmacological properties, as we have observed anomalous tetraethylammonium (TEA) sensitivity in the native K(O2) currents. DPPX association with Kv4 channels induced an increased TEA sensitivity both in heterologous expression systems and in CB chemoreceptor cells. Moreover, TEA application to Kv4-DPPX heteromultimers leads to marked kinetic effects that could be explained by an augmented closed-state inactivation. Our data suggest that DPPX proteins are integral components of K(O2) currents, and that their association with Kv4 subunits modulate the pharmacological profile of the heteromultimers.

  12. Voltage-dependent gating and gating charge measurements in the Kv1.2 potassium channel

    PubMed Central

    Ishida, Itzel G.; Rangel-Yescas, Gisela E.; Carrasco-Zanini, Julia

    2015-01-01

    Much has been learned about the voltage sensors of ion channels since the x-ray structure of the mammalian voltage-gated potassium channel Kv1.2 was published in 2005. High resolution structural data of a Kv channel enabled the structural interpretation of numerous electrophysiological findings collected in various ion channels, most notably Shaker, and permitted the development of meticulous computational simulations of the activation mechanism. The fundamental premise for the structural interpretation of functional measurements from Shaker is that this channel and Kv1.2 have the same characteristics, such that correlation of data from both channels would be a trivial task. We tested these assumptions by measuring Kv1.2 voltage-dependent gating and charge per channel. We found that the Kv1.2 gating charge is near 10 elementary charges (eo), ∼25% less than the well-established 13–14 eo in Shaker. Next, we neutralized positive residues in the Kv1.2 S4 transmembrane segment to investigate the cause of the reduction of the gating charge and found that, whereas replacing R1 with glutamine decreased voltage sensitivity to ∼50% of the wild-type channel value, mutation of the subsequent arginines had a much smaller effect. These data are in marked contrast to the effects of charge neutralization in Shaker, where removal of the first four basic residues reduces the gating charge by roughly the same amount. In light of these differences, we propose that the voltage-sensing domains (VSDs) of Kv1.2 and Shaker might undergo the same physical movement, but the septum that separates the aqueous crevices in the VSD of Kv1.2 might be thicker than Shaker’s, accounting for the smaller Kv1.2 gating charge. PMID:25779871

  13. 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.

  14. Rotorcraft transmission

    NASA Technical Reports Server (NTRS)

    Coy, John J.

    1987-01-01

    The NASA Lewis Research Center and the U.S. Army Aviation Systems Command share an interest in advancing the technology for helicopter propulsion systems. In particular, this presentation outlines that portion of the program that applies to the drive train and its various mechanical components. The major goals of the program are to increase the life, reliability, and maintainability; reduce the weight, noise, and vibration; and maintain the relatively high mechanical efficiency of the gear train. The current activity emphasizes noise reduction technology and analytical code development followed by experimental verification. Selected significant advances in technology for transmissions are reviewed, including advanced configurations and new analytical tools. Finally, the plan for transmission research in the future is presented.

  15. Supplement Analysis for the Transmission System Vegetation Management Program FEIS (DOE/EIS- 0285/SA-33)

    SciTech Connect

    Stratton, Elaine

    2001-11-27

    Vegetation Management along the St Helens-Allston Transmission Line ROW. The line is a 115 kV Single Circuit Transmission Line having an easement width of 100 feet. BPA proposes to clear danger trees from varying widths of the indicated transmission line right-of-way that are approaching electrical clearance zones in accordance with the National Electrical Safety Code and BPA Standards. See Section 1.1 of the attached checklist for pertinent information on each section of referenced transmission line. BPA is clearing the danger trees to prevent them from falling or growing into the lines, thereby causing outages.

  16. 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. PMID:25231973

  17. 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).

  18. 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.

  19. 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.

  20. O2-sensitive K+ channels: role of the Kv1.2 -subunit in mediating the hypoxic response.

    PubMed

    Conforti, L; Bodi, I; Nisbet, J W; Millhorn, D E

    2000-05-01

    One of the early events in O2 chemoreception is inhibition of O2-sensitive K+ (KO2) channels. Characterization of the molecular composition of the native KO2 channels in chemosensitive cells is important to understand the mechanism(s) that couple O2 to the KO2 channels. The rat phaeochromocytoma PC12 clonal cell line expresses an O2-sensitive voltage-dependent K+ channel similar to that recorded in other chemosensitive cells. Here we examine the possibility that the Kv1.2 alpha-subunit comprises the KO2 channel in PC12 cells. Whole-cell voltage-clamp experiments showed that the KO2 current in PC12 cells is inhibited by charybdotoxin, a blocker of Kv1.2 channels. PC12 cells express the Kv1.2 alpha-subunit of K+ channels: Western blot analysis with affinity-purified anti-Kv1.2 antibody revealed a band at approximately 80 kDa. Specificity of this antibody was established in Western blot and immunohystochemical studies. Anti-Kv1.2 antibody selectively blocked Kv1.2 current expressed in the Xenopus oocyte, but had no effect on Kv2.1 current. Anti-Kv1.2 antibody dialysed through the patch pipette completely blocked the KO2 current, while the anti-Kv2.1 and irrelevant antibodies had no effect. The O2 sensitivity of recombinant Kv1.2 and Kv2.1 channels was studied in Xenopus oocytes. Hypoxia inhibited the Kv1.2 current only. These findings show that the KO2 channel in PC12 cells belongs to the Kv1 subfamily of K+ channels and that the Kv1.2 alpha-subunit is important in conferring O2 sensitivity to this channel. PMID:10790158

  1. O2-sensitive K+ channels: role of the Kv1.2 α-subunit in mediating the hypoxic response

    PubMed Central

    Conforti, Laura; Bodi, Ilona; Nisbet, John W; Millhorn, David E

    2000-01-01

    One of the early events in O2 chemoreception is inhibition of O2-sensitive K+ (KO2) channels. Characterization of the molecular composition of the native KO2 channels in chemosensitive cells is important to understand the mechanism(s) that couple O2 to the KO2 channels. The rat phaeochromocytoma PC12 clonal cell line expresses an O2-sensitive voltage-dependent K+ channel similar to that recorded in other chemosensitive cells. Here we examine the possibility that the Kv1.2 α-subunit comprises the KO2 channel in PC12 cells. Whole-cell voltage-clamp experiments showed that the KO2 current in PC12 cells is inhibited by charybdotoxin, a blocker of Kv1.2 channels. PC12 cells express the Kv1.2 α-subunit of K+ channels: Western blot analysis with affinity-purified anti-Kv1.2 antibody revealed a band at ≈80 kDa. Specificity of this antibody was established in Western blot and immunohystochemical studies. Anti-Kv1.2 antibody selectively blocked Kv1.2 current expressed in the Xenopus oocyte, but had no effect on Kv2.1 current. Anti-Kv1.2 antibody dialysed through the patch pipette completely blocked the KO2 current, while the anti-Kv2.1 and irrelevant antibodies had no effect. The O2 sensitivity of recombinant Kv1.2 and Kv2.1 channels was studied in Xenopus oocytes. Hypoxia inhibited the Kv1.2 current only. These findings show that the KO2 channel in PC12 cells belongs to the Kv1 subfamily of K+ channels and that the Kv1.2 α-subunit is important in conferring O2 sensitivity to this channel. PMID:10790158

  2. Intravascular pressure enhances the abundance of functional Kv1.5 channels at the surface of arterial smooth muscle cells.

    PubMed

    Kidd, Michael W; Leo, M Dennis; Bannister, John P; Jaggar, Jonathan H

    2015-08-18

    Voltage-dependent potassium (K(v)) channels are present in various cell types, including smooth muscle cells (myocytes) of resistance-sized arteries that control systemic blood pressure and regional organ blood flow. Intravascular pressure depolarizes arterial myocytes, stimulating calcium (Ca(2+)) influx through voltage-dependent Ca(2+) (Ca(v)) channels that results in vasoconstriction and also K(+) efflux through K(v) channels that oppose vasoconstriction. We hypothesized that pressure-induced depolarization may not only increase the open probability of plasma membrane-resident K(v) channels but also increase the abundance of these channels at the surface of arterial myocytes to limit vasoconstriction. We found that K(v)1.5 and K(v)2.1 proteins were abundant in the myocytes of resistance-sized mesenteric arteries. K(v)1.5, but not K(v)2.1, continuously recycled between the intracellular compartment and the plasma membrane in contractile arterial myocytes. Using ex vivo preparations of intact arteries, we showed that physiological intravascular pressure through membrane depolarization or membrane depolarization in the absence of pressure inhibited the degradation of internalized K(v)1.5 and increased recycling of K(v)1.5 to the plasma membrane. Accordingly, by stimulating the activity of Ca(v)1.2, membrane depolarization increased whole-cell K(v)1.5 current density in myocytes and K(v)1.5 channel activity in pressurized arteries. In contrast, the total amount and cell surface abundance of K(v)2.1 were independent of intravascular pressure or membrane potential. Thus, our data indicate that intravascular pressure-induced membrane depolarization selectively increased K(v)1.5 surface abundance to increase K(v) currents in arterial myocytes, which would limit vasoconstriction.

  3. E3 ligase CHIP and Hsc70 regulate Kv1.5 protein expression and function in mammalian cells.

    PubMed

    Li, Peili; Kurata, Yasutaka; Maharani, Nani; Mahati, Endang; Higaki, Katsumi; Hasegawa, Akira; Shirayoshi, Yasuaki; Yoshida, Akio; Kondo, Tatehito; Kurozawa, Youichi; Yamamoto, Kazuhiro; Ninomiya, Haruaki; Hisatome, Ichiro

    2015-09-01

    Kv1.5 confers ultra-rapid delayed-rectifier potassium channel current (IKur) which contributes to repolarization of the atrial action potential. Kv1.5 proteins, degraded via the ubiquitin-proteasome pathway, decreased in some atrial fibrillation patients. Carboxyl-terminus heat shock cognate 70-interacting protein (CHIP), an E3 ubiquitin ligase, is known to ubiquitinate short-lived proteins. Here, we investigated the roles of CHIP in Kv1.5 degradation to provide insights into the mechanisms of Kv1.5 decreases and treatments targeting Kv1.5 for atrial fibrillation. Coexpression of CHIP with Kv1.5 in HEK293 cells increased Kv1.5 protein ubiquitination and decreased the protein level. Immunofluorescence revealed decreases of Kv1.5 proteins in the endoplasmic reticulum and on the cell membrane. A siRNA against CHIP suppressed Kv1.5 protein ubiquitination and increased its protein level. CHIP mutants, lacking either the N-terminal tetratricopeptide region domain or the C-terminal U-box domain, failed to exert these effects on Kv1.5 proteins. Immunoprecipitation showed that CHIP formed complexes with Kv1.5 proteins and heat shock cognate protein 70 (Hsc70). Effects of Hsc70 on Kv1.5 were similar to CHIP by altering interaction of CHIP with Kv1.5 protein. Coexpression of CHIP and Hsc70 with Kv1.5 additionally enhanced Kv1.5 ubiquitination. Kv1.5 currents were decreased by overexpression of CHIP or Hsc70 but were increased by knockdown of CHIP or Hsc70 in HEK 293 cells stably expressing Kv1.5. These effects of CHIP and Hsc70 were also observed on endogenous Kv1.5 in HL-1 mouse cardiomyocytes, decreasing IKur and prolonging action potential duration. These results indicate that CHIP decreases the Kv1.5 protein level and functional channel by facilitating its degradation in concert with chaperone Hsc70.

  4. 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

  5. PKC and AMPK regulation of Kv1.5 potassium channels.

    PubMed

    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. 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.

  7. Automatic transmission

    SciTech Connect

    Ohkubo, M.

    1988-02-16

    An automatic transmission is described combining a stator reversing type torque converter and speed changer having first and second sun gears comprising: (a) a planetary gear train composed of first and second planetary gears sharing one planetary carrier in common; (b) a clutch and requisite brakes to control the planetary gear train; and (c) a speed-increasing or speed-decreasing mechanism is installed both in between a turbine shaft coupled to a turbine of the stator reversing type torque converter and the first sun gear of the speed changer, and in between a stator shaft coupled to a reversing stator and the second sun gear of the speed changer.

  8. Automatic transmission

    SciTech Connect

    Miki, N.

    1988-10-11

    This patent describes an automatic transmission including a fluid torque converter, a first gear unit having three forward-speed gears and a single reverse gear, a second gear unit having a low-speed gear and a high-speed gear, and a hydraulic control system, the hydraulic control system comprising: a source of pressurized fluid; a first shift valve for controlling the shifting between the first-speed gear and the second-speed gear of the first gear unit; a second shift valve for controlling the shifting between the second-speed gear and the third-speed gear of the first gear unit; a third shift valve equipped with a spool having two positions for controlling the shifting between the low-speed gear and the high-speed gear of the second gear unit; a manual selector valve having a plurality of shift positions for distributing the pressurized fluid supply from the source of pressurized fluid to the first, second and third shift valves respectively; first, second and third solenoid valves corresponding to the first, second and third shift valves, respectively for independently controlling the operation of the respective shift valves, thereby establishing a six forward-speed automatic transmission by combining the low-speed gear and the high-speed gear of the second gear unit with each of the first-speed gear, the second speed gear and the third-speed gear of the first gear unit; and means to fixedly position the spool of the third shift valve at one of the two positions by supplying the pressurized fluid to the third shift valve when the manual selector valve is shifted to a particular shift position, thereby locking the second gear unit in one of low-speed gear and the high-speed gear, whereby the six forward-speed automatic transmission is converted to a three forward-speed automatic transmission when the manual selector valve is shifted to the particular shift position.

  9. A 600-kV double-pulser for the PHERMEX electron gun

    SciTech Connect

    Carlson, R.L.; Kang, M.; Melton, J.G.; Seitz, G.J.; Trujillo, L.T.

    1997-09-01

    The PHERMEX (Pulsed High Energy Radiographic Machine Emitting X-rays) Radiographic Facility is a 50-MHz, 3-Cavity, RF-Linac driven by a pulsed, thermionic electron-gun Injector. The PHERMEX is used to take flash radiographs using x-rays at a single time in an explosively driven event. To investigate the time evolution of these events requires two things: (1) a multiple-pulser to drive the electron-gun Injector and (2) a large-format, gamma-ray, camera system to record a scintillator at the different times. The authors report the recent success of developing a reliable double-pulser that consists of two Marx generators that independently charge two PFLs that are switched out at about 1.4 MV. The PFLs are connected in series by large diaphragm switches that are independently laser triggered by two quadrupled-YAG lasers. Recent tests of the system into a dummy load, produced two high quality 600 kV pulses separated by 1.0 {micro}s. Each pulse has a FWHM of 90 ns, a 50 ns flat-top {+-} 3%, and a risetime of 25 ns and a falltime of 35 ns. The interpulse time is variable up to about 275 {micro}s; the first switch is kept closed by a keep alive inductor. The system has produced a 50 shot sequence of two pulses with a 1-sigma jitter < 1 ns. The system has been modeled using TOSCA-3D, FLUX-2D, and a transmission line model run with the circuits code Micro-CAP.

  10. Distinct Cell- and Layer-Specific Expression Patterns and Independent Regulation of Kv2 Channel Subtypes in Cortical Pyramidal Neurons

    PubMed Central

    Bishop, Hannah I.; Guan, Dongxu; Bocksteins, Elke; Parajuli, Laxmi Kumar; Murray, Karl D.; Cobb, Melanie M.; Misonou, Hiroaki; Zito, Karen; Foehring, Robert C.

    2015-01-01

    The Kv2 family of voltage-gated potassium channel α subunits, comprising Kv2.1 and Kv2.2, mediate the bulk of the neuronal delayed rectifier K+ current in many mammalian central neurons. Kv2.1 exhibits robust expression across many neuron types and is unique in its conditional role in modulating intrinsic excitability through changes in its phosphorylation state, which affect Kv2.1 expression, localization, and function. Much less is known of the highly related Kv2.2 subunit, especially in forebrain neurons. Here, through combined use of cortical layer markers and transgenic mouse lines, we show that Kv2.1 and Kv2.2 are localized to functionally distinct cortical cell types. Kv2.1 expression is consistently high throughout all cortical layers, especially in layer (L) 5b pyramidal neurons, whereas Kv2.2 expression is primarily limited to neurons in L2 and L5a. In addition, L4 of primary somatosensory cortex is strikingly devoid of Kv2.2 immunolabeling. The restricted pattern of Kv2.2 expression persists in Kv2.1-KO mice, suggesting distinct cell- and layer-specific functions for these two highly related Kv2 subunits. Analyses of endogenous Kv2.2 in cortical neurons in situ and recombinant Kv2.2 expressed in heterologous cells reveal that Kv2.2 is largely refractory to stimuli that trigger robust, phosphorylation-dependent changes in Kv2.1 clustering and function. Immunocytochemistry and voltage-clamp recordings from outside-out macropatches reveal distinct cellular expression patterns for Kv2.1 and Kv2.2 in intratelencephalic and pyramidal tract neurons of L5, indicating circuit-specific requirements for these Kv2 paralogs. Together, these results support distinct roles for these two Kv2 channel family members in mammalian cortex. SIGNIFICANCE STATEMENT Neurons within the neocortex are arranged in a laminar architecture and contribute to the input, processing, and/or output of sensory and motor signals in a cell- and layer-specific manner. Neurons of different

  11. Block of Kv4.3 potassium channel by trifluoperazine independent of CaMKII.

    PubMed

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

    2014-08-22

    Trifluoperazine, a trifluoro-methyl phenothiazine derivative, is widely used in the management of schizophrenia and related psychotic disorders. We studied the effects of trifluoperazine on Kv4.3 currents expressed in CHO cells using the whole-cell patch-clamp technique. Trifluoperazine blocked Kv4.3 in a concentration-dependent manner with an IC50 value of 8.0±0.4 μM and a Hill coefficient of 2.1±0.1. Trifluoperazine also accelerated the inactivation and activation (time-to-peak) kinetics in a concentration-dependent manner. The effects of trifluoperazine on Kv4.3 were completely reversible after washout. The effects of trifluoperazine were not affected by the pretreatment of KN93, which is another CaMKII inhibitor. In addition, the inclusion of CaMKII inhibitory peptide 281-309 in the pipette solution did not modify the effect of trifluoperazine on Kv4.3. Trifluoperazine shifted the activation curve of Kv4.3 in a hyperpolarizing direction but did not affect the slope factor. The block of Kv4.3 by trifluoperazine was voltage-dependent with a steep increase across the voltage range of channel activation. Voltage dependence was also observed over the full range of activation (δ=0.18). Trifluoperazine slowed the time course for recovery from inactivation of Kv4.3. Our results indicated that trifluoperazine blocked Kv4.3 by preferentially binding to the open state of the channel. This effect was not mediated via the inhibition of CaMKII activity.

  12. 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

  13. Note: A rectangular pulse generator for 50 kV voltage, 0.8 ns rise time, and 10 ns pulse width based on polymer-film switch.

    PubMed

    Wu, Hanyu; Zhang, Xinjun; Sun, Tieping; Zeng, Zhengzhong; Cong, Peitian; Zhang, Shaoguo

    2015-10-01

    In this article, we describe a rectangular pulse generator, consisting of a polymer-film switch, a tri-plate transmission line, and parallel post-shaped ceramic resistor load, for 50-kV voltage, 0.8-ns rise time, and 10-ns width. The switch and resistors are arranged in atmospheric air and the transmission line can work in atmospheric air or in transformer oil to change the pulse width from 6.7 ns to 10 ns. The fast switching and low-inductance characteristics of the polymer-film switch ensure the fast rising wavefront of <1 ns. This generator can be applied in the calibration of nanosecond voltage dividers and used for electromagnetic pulse tests as a fast-rising current injection source. PMID:26521006

  14. Automatic transmission

    SciTech Connect

    Aoki, H.

    1989-03-21

    An automatic transmission is described, comprising: a torque converter including an impeller having a connected member, a turbine having an input member and a reactor; and an automatic transmission mechanism having first to third clutches and plural gear units including a single planetary gear unit with a ring gear and a dual planetary gear unit with a ring gear. The single and dual planetary gear units have respective carriers integrally coupled with each other and respective sun gears integrally coupled with each other, the input member of the turbine being coupled with the ring gear of the single planetary gear unit through the first clutch, and being coupled with the sun gear through the second clutch. The connected member of the impeller is coupled with the ring gear of the dual planetary gear of the dual planetary gear unit is made to be and ring gear of the dual planetary gear unit is made to be restrained as required, and the carrier is coupled with an output member.

  15. 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. PMID:22438204

  16. Temporal and spatial patterns of Kv1.1 and Kv1.2 protein and gene expression in spinal cord white matter after acute and chronic spinal cord injury in rats: implications for axonal pathophysiology after neurotrauma.

    PubMed

    Karimi-Abdolrezaee, Soheila; Eftekharpour, Eftekhar; Fehlings, Michael G

    2004-02-01

    After spinal cord injury (SCI), surviving white matter axons display axonal dysfunction associated with demyelination and altered K+ channel activity. To clarify the molecular basis of posttraumatic axonal pathophysiology after SCI, we investigated the changes in expression and distribution of the axonal K+ channel subunits Kv1.1 and Kv1.2 in spinal cord white matter after in vivo SCI in the rat. Using Western blot analysis, we found an increased expression of Kv1.1 and Kv1.2 at 2 and 6 weeks after SCI. By real-time PCR we observed an increase in Kv1.1 and Kv1.2 mRNA levels 1 day after SCI, which persisted until 6 weeks. Confocal immunohistochemistry showed a markedly dispersed labelling of Kv1.1 and Kv1.2 along the injured axons, in contrast to the tight localization of these channels to the juxtaparanodes of noninjured axons. This redistribution of Kv1.1 and Kv1.2 occurred as early as 1 h postinjury along some injured axons, and persisted at 6 weeks postinjury. In parallel with the redistribution of Kv1.1 and 1.2, contactin-associated protein (Caspr), which is normally confined to a paranodal location, also displayed a more diffuse distribution along the injured spinal cord axons. Our results suggest that the increased expression of Kv1.1 and Kv1.2 proteins is transcriptionally regulated. In contrast, the redistribution of the axonal K+ channel subunits occurs very early postinjury and probably reflects a disruption of the juxtaparanodal axonal region due to physical trauma, as shown by altered localization of Caspr. PMID:14984408

  17. Molecular identification of Kvα subunits that contribute to the oxygen-sensitive K+ current of chemoreceptor cells of the rabbit carotid body

    PubMed Central

    Sanchez, Diego; López-López, Jose R; Pérez-García, M Teresa; Sanz-Alfayate, Gloria; Obeso, Ana; Ganfornina, Maria D; Gonzalez, Constancio

    2002-01-01

    Rabbit carotid body (CB) chemoreceptor cells possess a fast-inactivating K+ current that is specifically inhibited by hypoxia. We have studied the expression of Kvα subunits, which might be responsible for this current. RT-PCR experiments identified the expression of Kv1.4, Kv3.4, Kv4.1 and Kv4.3 mRNAs in the rabbit CB. There was no expression of Kv3.3 or Kv4.2 transcripts. Immunocytochemistry with antibodies to tyrosine hydroxylase (anti-TH) and to specific Kv subunits revealed the expression of Kv3.4 and Kv4.3 in chemoreceptor cells, while Kv1.4 was only found in nerve fibres. Kv4.1 mRNA was also found in chemoreceptor cells following in situ hybridization combined with anti-TH antibody labelling. Kv4.1 and Kv4.3 appeared to be present in all chemoreceptor cells, but Kv3.4 was only expressed in a population of them. Electrophysiological experiments applying specific toxins or antibodies demonstrated that both Kv3.4 and Kv4.3 participate in the oxygen-sensitive K+ current of chemoreceptor cells. However, toxin application experiments confirmed a larger contribution of members of the Kv4 subfamily. [Ca2+]i measurements under hypoxic conditions and immunocytochemistry experiments in dispersed CB cells demonstrated the expression of Kv3.4 and Kv4.3 in oxygen-sensitive cells; the presence of Kv3.4 in the chemoreceptor cell membrane was not required for the response to low PO2. In summary, three Kv subunits (Kv3.4, Kv4.1 and Kv4.3) may be involved in the fast-inactivating outward K+ current of rabbit CB chemoreceptor cells. The homogeneous distribution of the Kv4 subunits in chemoreceptor cells, along with their electrophysiological properties, suggest that Kv4.1, Kv4.3, or their heteromultimers, are the molecular correlate of the oxygen-sensitive K+ channel. PMID:12122138

  18. 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

  19. Immunomodulatory effects of diclofenac in leukocytes through the targeting of Kv1.3 voltage-dependent potassium channels.

    PubMed

    Villalonga, Núria; David, Miren; Bielańska, Joanna; González, Teresa; Parra, David; Soler, Concepció; Comes, Núria; Valenzuela, Carmen; Felipe, Antonio

    2010-09-15

    Kv1.3 plays a crucial role in the activation and proliferation of T-lymphocytes and macrophages. While Kv1.3 is responsible for the voltage-dependent potassium current in T-cells, in macrophages this K(+) current is generated by the association of Kv1.3 and Kv1.5. Patients with autoimmune diseases show a high number of effector memory T cells that are characterized by a high expression of Kv1.3 and Kv1.3 antagonists ameliorate autoimmune disorders in vivo. Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) used in patients who suffer from painful autoimmune diseases such as rheumatoid arthritis. In this study, we show that diclofenac impairs immune response via a mechanism that involves Kv1.3. While diclofenac inhibited Kv1.3 expression in activated macrophages and T-lymphocytes, Kv1.5 remained unaffected. Diclofenac also decreased iNOS levels in Raw 264.7 cells, impairing their activation in response to lipopolysaccharide (LPS). LPS-induced macrophage migration and IL-2 production in stimulated Jurkat T-cells were also blocked by pharmacological doses of diclofenac. These effects were mimicked by Margatoxin, a specific Kv1.3 inhibitor, and Charybdotoxin, which blocks both Kv1.3 and Ca(2+)-activated K(+) channels (K(Ca)3.1). Because Kv1.3 is a very good target for autoimmune therapies, the effects of diclofenac on Kv1.3 are of high pharmacological relevance.

  20. Overdrive transmission

    SciTech Connect

    Miller, G.F.

    1986-02-04

    This patent describes an overdrive transmission device for use with a motor vehicle. It consists of: a housing; a driving shaft rotatably mounted within the housing; a planetary gear-train; a driven shaft rotatably mounted in the housing and driven by the planetary gear train; and, a device for selectively connecting the planetary gear carrier to the housing or to the driven shaft for rotation; a hydraulically actuated piston adapted to forcibly contact the clutch friction members of the second clutch; a source of working fluid; a pump in fluid flow communication with the source of working fluid; a first valve downstream of the pump and in fluid flow communication with the pump and the hydraulically activated piston.

  1. Planetary transmission

    SciTech Connect

    Nerstad, K.A.; Windish, W.E.

    1987-04-21

    A planetary transmission is described comprising: an input shaft; a first planetary gear set having a first sun gear driven by the input shaft, a first planet carrier serving as the output, a first ring gear, and first brake means for selectively holding the fist ring gear stationary; a second planetary gear set having a second sun gear driven by the input shaft, a second planet carrier connected for joint rotation to the first ring gear, a second ring gear, and second brake means for selectively holding the second ring gear stationary; a third planetary gear set having a third sun gear connected for joint rotation to the second planet carrier, a third planet carrier connected for joint rotation to the second ring gear, a third ring gear, and third brake means for selectively holding the third ring gear stationary; and clutch means for connecting the third sun gear to the input shaft and providing a direct drive mode of operation.

  2. 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

  3. A comparison of the effectiveness of 28 kV (grid) versus 25 kV (no grid) mammographic techniques for breast screening.

    PubMed

    Warren, R M; Duffy, S

    1997-10-01

    The purpose of this study was to compare the clinical effectiveness of breast screening using a mammographic technique of 25 kV without a grid, with one of 28 kV with a grid. Effectiveness is judged by cancer detection, interval cancer rates, sensitivity and specificity calculations and tumour characteristics. The doses on standard physics tests given by the three machines when these exposure factors are selected were compared to see whether there is any scientific basis for recommendations on which is the more effective technique. The experiment was undertaken in the prevalence round of a screening programme set up in the UK in 1987. The main comparison is on 25,078 women randomized to one or other technique after March 1989. Comparison can also be made with the preceding 8482 women, who were examined by the 25 kV method, but not randomized and in whom there were a variety of other differences. In the randomized group there was no statistically significant difference in cancer detection. A minor difference in overall numbers without statistical significance was seen in favour of the 28 kV grid technique, but is offset by a greater interval cancer rate in this group. Small cancer detection was equal in the two groups. By contrast, the first 8482 women showed significantly worse screening performance, both in lower overall and small cancer detection rate, and in increased number of interval cancers, for which the explanation is likely to be complex. The dose measurements show that the use of a higher tube potential with the grid mitigates the dose increase that may have been expected. The choice between these two techniques is therefore neither automatically made by greater cancer detection nor made on grounds of dose. There was a minor dose penalty in using the 28 kV technique with grid. PMID:9404206

  4. PIST (GOPC) modulates the oncogenic voltage-gated potassium channel KV10.1

    PubMed Central

    Herrmann, Solveig; Ninkovic, Milena; Kohl, Tobias; Pardo, Luis A.

    2013-01-01

    Although crucial for their correct function, the mechanisms controlling surface expression of ion channels are poorly understood. In the case of the voltage-gated potassium channel KV10.1, this is determinant not only for its physiological function in brain, but also for its pathophysiology in tumors and possible use as a therapeutic target. The Golgi resident protein PIST binds several membrane proteins, thereby modulating their expression. Here we describe a PDZ domain-mediated interaction of KV10.1 and PIST, which enhances surface levels of KV10.1. The functional, but not the physical interaction of both proteins is dependent on the coiled-coil and PDZ domains of PIST; insertion of eight amino acids in the coiled-coil domain to render the neural form of PIST (nPIST) and the corresponding short isoform in an as-of-yet unknown form abolishes the effect. In addition, two new isoforms of PIST (sPIST and nsPIST) lacking nearly the complete PDZ domain were cloned and shown to be ubiquitously expressed. PIST and KV10.1 co-precipitate from native and expression systems. nPIST also showed interaction, but did not alter the functional expression of the channel. We could not document physical interaction between KV10.1 and sPIST, but it reduced KV10.1 functional expression in a dominant-negative manner. nsPIST showed weak physical interaction and no functional effect on KV10.1. We propose these isoforms to work as modulators of PIST function via regulating the binding on interaction partners. PMID:23966943

  5. The Novel KV7.2/KV7.3 Channel Opener ICA-069673 Reveals Subtype-Specific Functional Roles in Guinea Pig Detrusor Smooth Muscle Excitability and Contractility.

    PubMed

    Provence, Aaron; Malysz, John; Petkov, Georgi V

    2015-09-01

    The physiologic roles of voltage-gated KV7 channel subtypes (KV7.1-KV7.5) in detrusor smooth muscle (DSM) are poorly understood. Here, we sought to elucidate the functional roles of KV7.2/KV7.3 channels in guinea pig DSM excitability and contractility using the novel KV7.2/KV7.3 channel activator ICA-069673 [N-(2-chloro-5-pyrimidinyl)-3,4-difluorobenzamide]. We employed a multilevel experimental approach using Western blot analysis, immunocytochemistry, isometric DSM tension recordings, fluorescence Ca(2+) imaging, and perforated whole-cell patch-clamp electrophysiology. Western blot experiments revealed the protein expression of KV7.2 and KV7.3 channel subunits in DSM tissue. In isolated DSM cells, immunocytochemistry with confocal microscopy further confirmed protein expression for KV7.2 and KV7.3 channel subunits, where they localize within the vicinity of the cell membrane. ICA-069673 inhibited spontaneous phasic, pharmacologically induced, and nerve-evoked contractions in DSM isolated strips in a concentration-dependent manner. The inhibitory effects of ICA-069673 on DSM spontaneous phasic and tonic contractions were abolished in the presence of the KV7 channel inhibitor XE991 [10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone dihydrochloride]. Under conditions of elevated extracellular K(+) (60 mM), the effects of ICA-069673 on DSM tonic contractions were significantly attenuated. ICA-069673 decreased the global intracellular Ca(2+) concentration in DSM cells, an effect blocked by the L-type Ca(2+) channel inhibitor nifedipine. ICA-069673 hyperpolarized the membrane potential and inhibited spontaneous action potentials of isolated DSM cells, effects that were blocked in the presence of XE991. In conclusion, using the novel KV7.2/KV7.3 channel activator ICA-069673, this study provides strong evidence for a critical role for the KV7.2- and KV7.3-containing channels in DSM function at both cellular and tissue levels.

  6. Hydromechanical transmission

    DOEpatents

    Orshansky, Jr. deceased, Elias; Weseloh, William E.

    1978-01-01

    A power transmission having three planetary assemblies, each having its own carrier and its own planet, sun, and ring gears. A speed-varying module is connected in driving relation to the input shaft and in driving relationship to the three sun gears, all of which are connected together. The speed-varying means may comprise a pair of hydraulic units hydraulically interconnected so that one serves as a pump while the other serves as a motor and vice versa, one of the units having a variable stroke and being connected in driving relation to the input shaft, the other unit, which may have a fixed stroke, being connected in driving relation to the sun gears. The input shaft also drives the carrier of the third planetary assembly. A brake grounds the first carrier in the first range and in reverse and causes drive to be delivered to the output through the first ring gear in a hydrostatic mode. The carrier of the third planetary assembly drives the ring gear of the second planetary assembly, and a first clutching means connects the second carrier with the output in a second range, the brake for grounding the first carrier then being released. A second clutching means enables the third ring gear to drive the output shaft in a third range.

  7. 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

  8. Tracking single Kv2.1 channels in live cells reveals anomalous subdiffusion and ergodicity breaking

    NASA Astrophysics Data System (ADS)

    Weigel, Aubrey; Simon, Blair; Tamkun, Michael; Krapf, Diego

    2011-03-01

    The dynamic organization of the plasma membrane is responsible for essential cellular processes, such as receptor trafficking and signaling. By studying the dynamics of transmembrane proteins a greater understanding of these processes as a whole can be achieved. It is broadly observed that the diffusion pattern of membrane protein displays anomalous subdiffusion. However, the mechanisms responsible for this behavior are not yet established. We explore the dynamics of the voltage gated potassium channel Kv2.1 by using single-particle tracking. We analyze Kv2.1 channel trajectories in terms of the time and ensemble distributions of square displacements. Our results reveal that all Kv2.1 channels experience anomalous subdiffusion and we observe that the Kv2.1 diffusion pattern is non-ergodic. We further investigated the role of the actin cytoskeleton in these channel dynamics by applying actin depolymerizing drugs. It is seen that with the breakdown of the actin cytoskeleton the Kv2.1 channel trajectories recover ergodicity.

  9. Potassium Channel Kv1.3 Is Highly Expressed by Microglia in Human Alzheimer’s Disease

    PubMed Central

    Rangaraju, Srikant; Gearing, Marla; Jin, Lee-Way; Levey, Allan

    2015-01-01

    Recent genetic studies suggest a central role for innate immunity in Alzheimer’s disease (AD) pathogenesis, wherein microglia orchestrate neuroinflammation. Kv1.3, a voltage-gated potassium channel of therapeutic relevance in autoimmunity, is upregulated by activated microglia and mediates amyloid-mediated microglial priming and reactive oxygen species production in vitro. We hypothesized that Kv1.3 channel expression is increased in human AD brain tissue. In a blinded postmortem immunohistochemical semi-quantitative analysis performed on ten AD patients and ten non-disease controls, we observed a significantly higher Kv1.3 staining intensity (p = 0.03) and Kv1.3-positive cell density (p = 0.03) in the frontal cortex of AD brains, compared to controls. This paralleled an increased number of Iba1-positive microglia in AD brains. Kv1.3-positive cells had microglial morphology and were associated with amyloid-β plaques. In immunofluorescence studies, Kv1.3 channels co-localized primarily with Iba1 but not with astrocyte marker GFAP, confirming that elevated Kv1.3 expression is limited to microglia. Higher Kv1.3 expression in AD brains was also confirmed by western blot analysis. Our findings support that Kv1.3 channels are biologically relevant and microglia-specific targets in human AD. PMID:25362031

  10. Voltage-Gated K+ Channel, Kv3.3 Is Involved in Hemin-Induced K562 Differentiation

    PubMed Central

    Song, Min Seok; Choi, Seon Young; Ryu, Pan Dong; Lee, So Yeong

    2016-01-01

    Voltage-gated K+ (Kv) channels are well known to be involved in cell proliferation. However, even though cell proliferation is closely related to cell differentiation, the relationship between Kv channels and cell differentiation remains poorly investigated. This study demonstrates that Kv3.3 is involved in K562 cell erythroid differentiation. Down-regulation of Kv3.3 using siRNA-Kv3.3 increased hemin-induced K562 erythroid differentiation through decreased activation of signal molecules such as p38, cAMP response element-binding protein, and c-fos. Down-regulation of Kv3.3 also enhanced cell adhesion by increasing integrin β3 and this effect was amplified when the cells were cultured with fibronectin. The Kv channels, or at least Kv3.3, appear to be associated with cell differentiation; therefore, understanding the mechanisms of Kv channel regulation of cell differentiation would provide important information regarding vital cellular processes. PMID:26849432

  11. Selective down-regulation of KV2.1 function contributes to enhanced arterial tone during diabetes.

    PubMed

    Nieves-Cintrón, Madeline; Nystoriak, Matthew A; Prada, Maria Paz; Johnson, Kenneth; Fayer, William; Dell'Acqua, Mark L; Scott, John D; Navedo, Manuel F

    2015-03-20

    Enhanced arterial tone is a leading cause of vascular complications during diabetes. Voltage-gated K(+) (KV) channels are key regulators of vascular smooth muscle cells (VSMCs) contractility and arterial tone. Whether impaired KV channel function contributes to enhance arterial tone during diabetes is unclear. Here, we demonstrate a reduction in KV-mediated currents (IKv) in VSMCs from a high fat diet (HFD) mouse model of type 2 diabetes. In particular, IKv sensitive to stromatoxin (ScTx), a potent KV2 blocker, were selectively reduced in diabetic VSMCs. This was associated with decreased KV2-mediated regulation of arterial tone and suppression of the KV2.1 subunit mRNA and protein in VSMCs/arteries isolated from HFD mice. We identified protein kinase A anchoring protein 150 (AKAP150), via targeting of the phosphatase calcineurin (CaN), and the transcription factor nuclear factor of activated T-cells c3 (NFATc3) as required determinants of KV2.1 suppression during diabetes. Interestingly, substantial reduction in transcript levels for KV2.1 preceded down-regulation of large conductance Ca(2+)-activated K(+) (BKCa) channel β1 subunits, which are ultimately suppressed in chronic hyperglycemia to a similar extent. Together, our study supports the concept that transcriptional suppression of KV2.1 by activation of the AKAP150-CaN/NFATc3 signaling axis contributes to enhanced arterial tone during diabetes. PMID:25670860

  12. Development of Highly Selective Kv1.3-Blocking Peptides Based on the Sea Anemone Peptide ShK

    PubMed Central

    Pennington, Michael W.; Chang, Shih Chieh; Chauhan, Satendra; Huq, Redwan; Tajhya, Rajeev B.; Chhabra, Sandeep; Norton, Raymond S.; Beeton, Christine

    2015-01-01

    ShK, from the sea anemone Stichodactyla helianthus, is a 35-residue disulfide-rich peptide that blocks the voltage-gated potassium channel Kv1.3 at ca. 10 pM and the related channel Kv1.1 at ca. 16 pM. We developed an analog of this peptide, ShK-186, which is currently in Phase 1b-2a clinical trials for the treatment of autoimmune diseases such as multiple sclerosis and rheumatoid arthritis. While ShK-186 displays a >100-fold improvement in selectivity for Kv1.3 over Kv1.1 compared with ShK, there is considerable interest in developing peptides with an even greater selectivity ratio. In this report, we describe several variants of ShK that incorporate p-phophono-phenylalanine at the N-terminus coupled with internal substitutions at Gln16 and Met21. In addition, we also explored the combinatorial effects of these internal substitutions with an alanine extension at the C-terminus. Their selectivity was determined by patch-clamp electrophysiology on Kv1.3 and Kv1.1 channels stably expressed in mouse fibroblasts. The peptides with an alanine extension blocked Kv1.3 at low pM concentrations and exhibited up to 2250-fold selectivity for Kv1.3 over Kv1.1. Analogs that incorporates p-phosphono-phenylalanine at the N-terminus blocked Kv1.3 with IC50s in the low pM range and did not affect Kv1.1 at concentrations up to 100 nM, displaying a selectivity enhancement of >10,000-fold for Kv1.3 over Kv1.1. Other potentially important Kv channels such as Kv1.4 and Kv1.6 were only partially blocked at 100 nM concentrations of each of the ShK analogs. PMID:25603346

  13. Voltage-Sensitive K+ Channels Inhibit Parasympathetic Ganglion Transmission and Vagal Control of Heart Rate in Hypertensive Rats

    PubMed Central

    Berg, Torill

    2015-01-01

    Parasympathetic withdrawal plays an important role in the autonomic dysfunctions in hypertension. Since hyperpolarizing, voltage-sensitive K+ channels (KV) hamper transmitter release, elevated KV-activity may explain the disturbed vagal control of heart rate (HR) in hypertension. Here, the KV inhibitor 3,4-diaminopyridine was used to demonstrate the impact of KV on autonomic HR control. Cardiac output and HR were recorded by a flow probe on the ascending aorta in anesthetized, normotensive (WKY), and spontaneously hypertensive rats (SHR), and blood pressure by a femoral artery catheter. 3,4-diaminopyridine induced an initial bradycardia, which was greater in SHR than in WKY, followed by sustained tachycardia in both strains. The initial bradycardia was eliminated by acetylcholine synthesis inhibitor (hemicholinium-3) and nicotinic receptor antagonist/ganglion blocker (hexamethonium), and reversed to tachycardia by muscarinic receptor (mAchR) antagonist (atropine). The latter was abolished by sympatho-inhibition (reserpine). Reserpine also eliminated the late, 3,4-diaminopyridine-induced tachycardia in WKY, but induced a sustained atropine-sensitive bradycardia in SHR. Inhibition of the parasympathetic component with hemicholinium-3, hexamethonium, or atropine enhanced the late tachycardia in SHR, whereas hexamethonium reduced the tachycardia in WKY. In conclusion, 3,4-diaminopyridine-induced acetylcholine release, and thus enhanced parasympathetic ganglion transmission, with subsequent mAchR activation and bradycardia. 3,4-diaminopyridine also activated tachycardia, initially by enhancing sympathetic ganglion transmission, subsequently by activation of norepinephrine release from sympathetic nerve terminals. The 3,4-diaminopyridine-induced parasympathetic activation was stronger and more sustained in SHR, demonstrating an enhanced inhibitory control of KV on parasympathetic ganglion transmission. This enhanced KV activity may explain the dysfunctional vagal HR

  14. Power transmission

    SciTech Connect

    Ordo, J.P.; Raszkowski, J.A.; Klemen, D.

    1991-04-23

    This patent describes a transmission. It comprises a housing having first and second end covers; an input shaft rotatably mounted in the first end cover; an output shaft rotatably supported on the input shaft and in the second end cover; first and second countershafts rotatably supported in the end covers for rotation on respective axis parallel with the input shaft and the output shaft; a first head gear continuously rotatable with the input shaft; second and third head gears meshing with the first head gear and continuously rotatable with the first and second countershafts respectively; ratio gears rotatably supported on each of the countershafts including a first ratio gear on the first countershaft and a second ratio gear on the second countershaft; reverse gear means including a first ratio gear on the first countershaft and a second ratio gear on the second countershaft; reverse gear means including a first member rotatable with the first ratio gear means including a first member rotatable with the first ratio gear and a second member rotatably supported on the second countershaft; synchronizer clutch means selectively and alternatively connectible with the second ratio gear and the second member of the reverse gear means; output gear means drivingly connected with the output shaft and including a first ratio output gear meshing with the second ratio gear; first selectively engageable friction clutch means for connecting the first ratio gear with the first countershaft for completing a low forward drive ratio between the input and output shafts; and second selectively engageable friction clutch means for selectively connecting the synchronizer clutch means to the second countershaft and cooperating therewith to selectively alternatively complete a reverse drive ratio between the input shaft and the output shaft and another forward drive ratio between the input and output shafts.

  15. Automatic transmission

    SciTech Connect

    Miura, M.; Inuzuka, T.

    1986-08-26

    1. An automatic transmission with four forward speeds and one reverse position, is described which consists of: an input shaft; an output member; first and second planetary gear sets each having a sun gear, a ring gear and a carrier supporting a pinion in mesh with the sun gear and ring gear; the carrier of the first gear set, the ring gear of the second gear set and the output member all being connected; the ring gear of the first gear set connected to the carrier of the second gear set; a first clutch means for selectively connecting the input shaft to the sun gear of the first gear set, including friction elements, a piston selectively engaging the friction elements and a fluid servo in which hydraulic fluid is selectively supplied to the piston; a second clutch means for selectively connecting the input shaft to the sun gear of the second gear set a third clutch means for selectively connecting the input shaft to the carrier of the second gear set including friction elements, a piston selectively engaging the friction elements and a fluid servo in which hydraulic fluid is selectively supplied to the piston; a first drive-establishing means for selectively preventing rotation of the ring gear of the first gear set and the carrier of the second gear set in only one direction and, alternatively, in any direction; a second drive-establishing means for selectively preventing rotation of the sun gear of the second gear set; and a drum being open to the first planetary gear set, with a cylindrical intermediate wall, an inner peripheral wall and outer peripheral wall and forming the hydraulic servos of the first and third clutch means between the intermediate wall and the inner peripheral wall and between the intermediate wall and the outer peripheral wall respectively.

  16. Superconducting Fault Current Limiter for Transmission Voltage

    NASA Astrophysics Data System (ADS)

    Kraemer, Hans-Peter; Schmidt, Wolfgang; Cai, Hong; Gamble, Bruce; Madura, David; MacDonald, Tim; McNamara, Joe; Romanosky, Walther; Snitchler, Greg; Lallouet, Nicolas; Schmidt, Frank; Ahmed, Syed

    Within a collaboration of American Superconductor, Siemens, Nexans and Southern California Edison one electrical phase of a resistive superconducting fault current limiter for the 115 kV transmission voltage level has been designed and manufactured. The active part of the limiter consists of 63 bifilar coils made of 12 mm wide steel-stabilized YBCO conductor and is housed in a cryostat operated at 5 bar and 74 K. The first phase was completely assembled and successfully subjected to power switching tests and high voltage tests. The basic design of the system and the test results are reported. The work was funded in part by US-DOE under Contract Number DE-FC26-07NT43243.

  17. Hypoxia induces voltage-gated K+ (Kv) channel expression in pulmonary arterial smooth muscle cells through hypoxia-inducible factor-1 (HIF-1)

    PubMed Central

    Dong, Qian; Zhao, Ning; Xia, Cheng-kun; Du, Li-li; Fu, Xiao-xing; Du, Yi-mei

    2012-01-01

    Hypoxia-inducible factor-1 (HIF-1) regulates the expression of hypoxia-inducible genes by binding erythropoietin (EPO) enhancer fragments. Of these genes, HIF-1 upregulates voltage-gated K+1.2 channels (Kv1.2) in rat PC12 cells. Whether HIF-1 regulates hypoxia-induced Kv channel expression in cultured pulmonary artery smooth muscle cells (PASMCs), however, has not been determined. In this study, we investigated the effects of hypoxia on the expression of Kv1.2 Kv1.5, Kv2.1, and Kv9.3 channels in PASMCs and examined the direct role of HIF-1 by transfecting either wild type or mutant EPO enhancer fragments. Our results showed that 18 h exposure to hypoxia significantly increased the expression of Kv1.2, Kv1.5, Kv2.1, and Kv9.3; and this hypoxia-induced upregulation was completely inhibited after transfection with the wild type but not mutant EPO enhancer fragment. These results indicate that HIF-1 regulates hypoxia-stimulated induction of Kv1.2, Kv1.5, Kv2.1, and Kv9.3 channels in cultured PASMCs. PMID:22938542

  18. Performance of weathering steel in a transmission structure

    SciTech Connect

    Arasim, J.F.; Busch, D.W.

    1995-10-01

    A Florida utility company sought to evaluate the current condition of a typical transmission structure and determine the applicability of weathering steel in the South Florida environment. The structure, a 500 kV tubular steel pole tangent suspension structure, was removed from service and dissected. Visual inspections and metal thickness data were collected for the interior as well as the exterior. Results from the evaluation concluded that the transmission tower met or exceeded design expectations after 16 years of service with the exception of two identified areas of concern. Conclusions include how to avoid application problems in the design stage and how to retrofit existing structures. Weathering steels continue to be a viable option for tubular transmission structure applications because of their durability, low maintenance and reduced weights.

  19. Electric power transmission for a Hanford Nuclear Energy Center (HNEC)

    SciTech Connect

    Harty, H.; Dowis, W.J.

    1983-06-01

    The original study of transmission for a Hanford Nuclear Energy Center (HNEC), which was completed in September 1975, was updated in June 1978. The present 1983 revision takes cognizance of recent changes in the electric power situation of the PNW with respect to: (1) forecasts of load growth, (2) the feasibility of early use of 1100 kV transmission, and (3) the narrowing opportunities for siting nuclear plants in the region. The purpose of this update is to explore and describe additions to the existing transmission system that would be necessary to accommodate three levels of generation at HNEC. Comparisons with a PNW system having new thermal generating capacity distributed throughout the marketing region are not made as was done in earlier versions.

  20. Modulation of Kv7 potassium channels by a novel opener pyrazolo[1,5-a]pyrimidin-7(4H)-one compound QO-58

    PubMed Central

    Zhang, F; Mi, Y; Qi, JL; Li, JW; Si, M; Guan, BC; Du, XN; An, HL; Zhang, HL

    2013-01-01

    Background and Purpose Modulation of Kv7/M channel function represents a relatively new strategy to treat neuronal excitability disorders such as epilepsy and neuropathic pain. We designed and synthesized a novel series of pyrazolo[1,5-a] pyrimidin-7(4H)-one compounds, which activate Kv7 channels. Here, we characterized the effects of the lead compound, QO-58, on Kv7 channels and investigated its mechanism of action. Experimental Approach A perforated whole-cell patch technique was used to record Kv7 currents expressed in mammalian cell lines and M-type currents from rat dorsal root ganglion neurons. The effects of QO-58 in a rat model of neuropathic pain, chronic constriction injury (CCI) of the sciatic nerve, were also examined. Key Results QO-58 increased the current amplitudes, shifted the voltage-dependent activation curve in a more negative direction and slowed the deactivation of Kv7.2/Kv7.3 currents. QO-58 activated Kv7.1, Kv7.2, Kv7.4 and Kv7.3/Kv7.5 channels with a more selective effect on Kv7.2 and Kv7.4, but little effect on Kv7.3. The mechanism of QO-58's activation of Kv7 channels was clearly distinct from that used by retigabine. A chain of amino acids, Val224Val225Tyr226, in Kv7.2 was important for QO-58 activation of this channel. QO-58 enhanced native neuronal M currents, resulting in depression of evoked action potentials. QO-58 also elevated the pain threshold of neuropathic pain in the sciatic nerve CCI model. Conclusions and Implications The results indicate that QO-58 is a potent modulator of Kv7 channels with a mechanism of action different from those of known Kv7 openers. Hence, QO-58 shows potential as a treatment for diseases associated with neuronal hyperexcitability. PMID:23013484

  1. Characteristics of brain Kv1 channels tailored to mimic native counterparts by tandem linkage of alpha subunits: implications for K+ channelopathies.

    PubMed

    Akhtar, Sobia; Shamotienko, Oleg; Papakosta, Marianthi; Ali, Farooq; Dolly, J Oliver

    2002-05-10

    Most neuronal Kv1 channels contain Kv1.1, Kv1.2 alpha, and Kvbeta2.1 subunits, yet the influences of their stoichiometries on properties of the (alpha)(4)(beta)(4) variants remain undefined. cDNAs were engineered to contain 0, 1, 2, or 4 copies of Kv1.1 with the requisite number of Kv1.2 and co-expressed in mammalian cells with Kvbeta2.1 to achieve "native-like" hetero-oligomers. The monomeric (Kv1.1 or 1.2), dimeric (Kv1.1-1.2 or 1.2-1.2), and tetrameric (Kv1.1-(1.2)(3)) constructs produced proteins of M(r) approximately 62,000, 120,000, and 240,000, which assembled into (alpha)(4)(beta)(4) complexes. Each alpha cRNA yielded a distinct K(+) current in oocytes, with voltage dependence of activation being shifted negatively as the Kv1.1 content in tetramers was increased. Channels containing 1, 2, or 4 copies of Kv1.1 were blocked by dendrotoxin k (DTX)(k) with similarly high potencies, whereas Kv(1.2)(4) proved nonsusceptible. Accordingly, Kv1.2/beta2.1 expressed in baby hamster kidney cells failed to bind DTX(k); in contrast, oligomers containing only one Kv1.1 subunit in a tetramer exhibited high affinity, with additional copies causing modest increases. Thus, one Kv1.1 subunit largely confers high affinity for DTX(k), whereas channel electrophysiological properties are tailored by the content of Kv1.1 relative to Kv1.2. This notable advance could explain the diversity of symptoms of human episodic ataxia I, which is often accompanied by myokymia, due to mutated Kv1.1 being assembled in different combinations with wild-type and Kv1.2.

  2. Study on Preserving Public Security of Installing 22 kV Distribution Equipment on Pavements

    NASA Astrophysics Data System (ADS)

    Murata, Koichi; Oka, Keisuke; Uemura, Satoshi; Ariga, Yasuo

    To cope with restructuring of electricity market, application of 22kV distribution systems to areas with high load density, is promising. To expand them, it is important to install 22kV distribution equipment on pavements and lots without fences. On the other hand, the neutral grounding method is expected for the 22kV distribution equipment in terms of rationalization of insulation. In this case, one line-to-ground fault current will be large. Therefore, to make safety of people, it is essential to decrease the contact voltage. In this paper, we will perform the simulation of current distribution in the case of one line-to-ground fault and study the security of human from the viewpoint of both step voltage and contact voltage. We will also clarify that we can lower the contact voltage by grounding mutually insulated inner box and outer box separately. Then we will propose the improved grounding method.

  3. Kv1.1 channel antisense attenuates learning and modulation of dentate polysialylated NCAM.

    PubMed

    Gratacós, E; Ghelardini, C; Gherardini, L M; Galeotti, N; Murphy, K J; Bartolini, A; Regan, C M

    1998-08-24

    The distribution and modulation of neural cell adhesion molecule polysialylation state (NCAM PSA) and the consequence of antisense inactivation of the Kv1.1 potassium channel was investigated following avoidance learning in mice. PSA immunoreactivity was most notable on cells at the inner denate border and in cortical layer II. Task acquisition resulted in a significant 30% transient increase in the frequency of dentate polysialylated neurons at the 12 h post-training time. In contrast, animals pretreated with the Kv1.1 antisense oligonucleotide exhibited both attenuated recall avoidance latencies and polysialylated cell frequency. As Kv1.1 is enriched on the dendrites of these granule-like cells, the attenuated polysialylation response is considered secondary to NCAM-mediated events during their transient synapse production in the 6-8 h post-training period.

  4. 600 kV modulator design for the SLAC Next Linear Collider Test Accelerator

    SciTech Connect

    Harris, K.; de Lamare, J.; Nesterov, V.; Cassel, R.

    1992-07-01

    Preliminary design for the SLAC Next Linear Collider Test Accelerator (NLCTA) requires a pulse power source to produce a 600 kV, 600 A, 1.4 {mu}s, 0.1% flat top pulse with rise and fall times of approximately 100 ns to power an X-Band klystron with a microperveance of 1.25 at {approx} 100 MW peak RF power. The design goals for the modulator, including those previously listed, are peak modulator pulse power of 340 MW operating at 120 Hz. A three-stage darlington pulse-forming network, which produces a >100 kV, 1.4 {mu}s pulse, is coupled to the klystron load through a 6:1 pulse transformer. Careful consideration of the transformer leakage inductance, klystron capacitance, system layout, and component choice is necessary to produce the very fast rise and fall times at 600 kV operating continuously at 120 Hz.

  5. Field Demonstration of a 24-kV Superconducting Cable at Detroit Edison

    SciTech Connect

    Kelley, Nathan; Corsaro, Pietro

    2004-12-01

    Customer acceptance of high temperature superconducting (HTS) cable technology requires a substantial field demonstration illustrating both the system's technical capabilities and its suitability for installation and operation within the utility environment. In this project, the world's first underground installation of an HTS cable using existing ductwork, a 120 meter demonstration cable circuit was designed and installed between the 24 kV bus distribution bus and a 120 kV-24 kV transformer at Detroit Edison's Frisbie substation. The system incorporated cables, accessories, a refrigeration system, and control instrumentation. Although the system was never put in operation because of problems with leaks in the cryostat, the project significantly advanced the state-of-the-art in the design and implementation of Warm Dielectric cable systems in substation applications. Lessons learned in this project are already being incorporated in several ongoing demonstration projects.

  6. Modulation of Kv3 potassium channels expressed in CHO cells by a nitric oxide-activated phosphatase

    PubMed Central

    Moreno, Herman; de Miera, Eleazar Vega-Saenz; Nadal, Marcela S; Amarillo, Yimy; Rudy, Bernardo

    2001-01-01

    Voltage-gated K+ channels containing Kv3 subunits play specific roles in the repolarization of action potentials. Kv3 channels are expressed in selective populations of CNS neurons and are thought to be important in facilitating sustained and/or repetitive high frequency firing. Regulation of the activity of Kv3 channels by neurotransmitters could have profound effects on the repetitive firing characteristics of those neurons. Kv3 channels are found in several neuronal populations in the CNS that express nitric oxide synthases (NOSs). We therefore investigated whether Kv3 channels are modulated by the signalling gas nitric oxide (NO). We found that Kv3.1 and Kv3.2 currents are potentially suppressed by D-NONOate and other NO donors. The effects of NO on these currents are mediated by the activation of guanylyl cyclase (GC), since they are prevented by Methylene Blue, an inhibitor of GC, and by ODQ, a specific inhibitor of the soluble form of GC. Moreover, application of 8-Br-cGMP, a permeant analogue of cGMP, also blocked Kv3.1 and Kv3.2 currents. KT5283, a cGMP-dependent protein kinase (PKG) blocker, prevented the inhibition of Kv3.1 and Kv3.2 currents by D-NONOate and 8-Br-cGMP. This indicates that activation of PKG as a result of the increase in intracellular cGMP levels produced by D-NONOate or 8-Br-cGMP is necessary for channel block. Although the effects of NO on Kv3.1 and Kv3.2 channels require PKG activity, two observations suggest that they are not mediated by phosphorylation of channel proteins: (a) the reagents affect both Kv3.2 and Kv3.1 channels, although only Kv3.2 proteins have a putative PKA-PKG phosphorylation site, and (b) mutation of the PKA-PKG phosphorylation site in Kv3.2 does not interfere with the effects of NO or cGMP. The inhibitory effects of NO and cGMP on Kv3.1 and Kv3.2 currents appear to be mediated by the activation of serine-threonine phosphatase, since they are blocked by low doses of okadaic acid. Furthermore, direct intracellular

  7. Magnetic activity and orbital period variation of the eclipsing binary KV Gem

    NASA Astrophysics Data System (ADS)

    Zhang, Liyun; Pi, Qingfeng; Yang, Yuangui; Li, Zhongmu

    2014-02-01

    This paper presents new CCD BVRI light curves of a neglected eclipsing binary KV Gem. Our new light curves were obtained in 2010 and 2011 at the Xinglong station of the National Astronomical Observatories, China. By analyzing all available light minimum times, we derived an update ephemeris and found there existed a cyclic variation overlaying a continuous period decrease. This kind of cyclic variation may probably be attributed to the light-time effect via the presence of an unseen third body or magnetic activity cycle. The long-term period decrease suggests that KV Gem is undergoing a mass transfer from the secondary component to the primary component at a rate of 3.4(0.3)×(10-7 M⊙/year for period decrease and a third body (10.3±0.2 years), and 5.5(0.6)×10-7 M⊙/year for decrease and magnetic cycle (8.8±0.1 years). By analyzing the light curves in 2011, photometric solutions and starspots parameters of the system are obtained using Wilson-Devinney program. Based on the photometric solution in 2011, we still could use the spot model to explain successfully our light curves in 2010 and three published light curves. Comparing the starspot longitudes and factors, KV Gem are variable on a long time scale of about years. For the data of KV Gem, the brightness vary with time around phases 0, 0.25, 0.5, and 0.75, which means that there is a possible photospheric active evolution. More data are needed to monitor to detect stellar cycle of KV Gem. For chromospheric activity of KV Gem, we found strong absorption in the observed Hβ,Hγ, and Ca II H & K spectra, and no obvious emission.

  8. The Role of Kv1.2 Channel in Electrotaxis Cell Migration

    PubMed Central

    Zhang, Gaofeng; Edmundson, Mathew; Telezhkin, Vsevolod; Gu, Yu; Wei, Xiaoqing; Kemp, Paul J.

    2015-01-01

    Voltage‐gated potassium Kv1.2 channels play pivotal role in maintaining of resting membrane potential and, consequently, regulation of cellular excitability of neurons. Endogenously generated electric field (EF) have been proven as an important regulator for cell migration and tissue repair. The mechanisms of ion channel involvement in EF‐induced cell responses are extensively studied but largely are poorly understood. In this study we generated three COS‐7 clones with different expression levels of Kv1.2 channel, and confirmed their functional variations with patch clamp analysis. Time‐lapse imaging analysis showed that EF‐induced cell migration response was Kv1.2 channel expression level depended. Inhibition of Kv1.2 channels with charybdotoxin (ChTX) constrained the sensitivity of COS‐7 cells to EF stimulation more than their motility. Immunocytochemistry and pull‐down analyses demonstrated association of Kv1.2 channels with actin‐binding protein cortactin and its re‐localization to the cathode‐facing membrane at EF stimulation, which confirms the mechanism of EF‐induced directional migration. This study displays that Kv1.2 channels represent an important physiological link in EF‐induced cell migration. The described mechanism suggests a potential application of EF which may improve therapeutic performance in curing injuries of neuronal and/or cardiac tissue repair, post operational therapy, and various degenerative syndromes. J. Cell. Physiol. 231: 1375–1384, 2016. © 2015 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. PMID:26580832

  9. Phosphoinositide 3-kinase dependent regulation of Kv channels in dendritic cells.

    PubMed

    Shumilina, Ekaterina; Zahir, Naima; Xuan, Nguyen Thi; Lang, Florian

    2007-01-01

    The phosphoinositide 3 (PI3) kinase plays a pivotal role in the regulation of dendritic cells (DCs), antigen-presenting cells that are able to initiate primary immune responses and to establish immunological memory. PI3 kinase is an endogenous suppressor of interleukin 12 (IL-12) production in DCs that is triggered by Toll-like receptor signaling. Inhibition of IL-12 production limits T helper 1 (Th1) polarization. On the other hand, PI3 kinase is an important regulator of various ion channels. The present study aimed to explore whether ion channels in DCs are regulated by PI3 kinase and whether they are important for DC function. To this end, DCs were isolated from murine bone marrow and ion channel activity was determined by patch clamp. As a result, DCs express voltage-gated K(+) channels (Kv), which are blocked by Stichodactyla helianthus toxin (ShK, 2.5 nM). A significant upregulation of Kv currents was observed upon maturation of DCs as induced by stimulation of the cells with lipopolysaccharide (LPS, 0.1 microg/ml, 48 h). A dramatic increase of Kv current amplitude was observed following preincubation of the cells with LY294002 (100 nM), a specific inhibitor of PI3 kinase. PI3 kinase inhibitor wortmannin (100 nM) similarly increased Kv current. LY294002 treatment was further followed by a significant increase of IL-12 production. ShK (100 nM) significantly blunted the stimulation of IL-12 release by LPS but not when the cells were first pretreated with LY294002. The observations point to Kv channel sensitive and Kv channel insensitive regulation of DC function. PMID:17982262

  10. Proteomic Analysis Highlights the Molecular Complexities of Native Kv4 Channel Macromolecular Complexes

    PubMed Central

    Marionneau, Céline; Townsend, R Reid; Nerbonne, Jeanne M

    2010-01-01

    Voltage-gated K+ (Kv) channels are key determinants of membrane excitability in the nervous and cardiovascular systems, functioning to control resting membrane potentials, shape action potential waveforms and influence the responses to neurotransmitters and neurohormones. Consistent with this functional diversity, multiple types of Kv currents, with distinct biophysical properties and cellular/subcellular distributions, have been identified. Rapidly activating and inactivating Kv currents, typically referred to as IA (A-type) in neurons, for example, regulate repetitive firing rates, action potential back-propagation (into dendrites) and modulate synaptic responses. Currents with similar properties, referred to as Ito,f (fast transient outward), expressed in cardiomyocytes, control the early phase of myocardial action potential repolarization. A number of studies have demonstrated critical roles for pore-forming (α) subunits of the Kv4 subfamily in the generation of native neuronal IA and cardiac Ito,f channels. Studies in heterologous cells have also suggested important roles for a number of Kv channel accessory and regulatory proteins in the generation of functional IA and Ito,f channels. Quantitative mass spectrometry-based proteomic analysis is increasingly recognized as a rapid and, importantly, unbiased, approach to identify the components of native macromolecular protein complexes. The recent application of proteomic approaches to identify the components of native neuronal (and cardiac) Kv4 channel complexes has revealed even greater complexity than anticipated. The continued emphasis on development of improved biochemical and analytical proteomics methods seems certain to accelerate progress and to provide important new insights into the molecular determinants of native ion channel protein complexes. PMID:20959143

  11. Kv1.3 channel blockade enhances the phagocytic function of RAW264.7 macrophages.

    PubMed

    Zhu, Hong; Yan, Li; Gu, JingLi; Hao, Wei; Cao, JiMin

    2015-09-01

    This study aimed to comprehend the largely unknown role of voltage-gated potassium channel 1.3 (Kv1.3) in the phagocytic function of macrophages. We found that blocking of the Kv1.3 channel with 100 pmol L(-1) Stichodactyla helianthus neurotoxin (ShK) enhanced the phagocytic capacities of both resting and lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages in the chicken erythrocyte system. In the fluorescein isothiocyanate (FITC)-labeled Escherichia coli k-12 system, ShK increased the phagocytic capacities of resting RAW264.7 cells, but not of the LPS-stimulated cells, as LPS alone stimulated almost saturated phagocytosis of the macrophages. ShK increased the nitric oxide (NO) production in LPS-activated cells, but not in resting RAW264.7 cells. There was no effect of ShK alone on the cytokine secretions in resting RAW264.7 cells, but it suppressed IL-1β secretion in LPS-stimulated RAW264.7 cells. At a concentration of 100 pmol L(-1), ShK did not affect the viability of the tested cells. Kv1.3 was expressed in RAW264.7 cells; this expression was downregulated by LPS, but significantly upregulated by disrupting caveolin-dependent endocytosis with filipin III. In addition, cytochalasin D, an inhibitor of actin polymerization, did not affect the Kv1.3 expression. Thus, blocking of the Kv1.3 channel enhances the phagocytic capacity and NO production of this cell line. Our results suggest that Kv1.3 channel serves as a negative regulator of phagocytosis in macrophages and can therefore be a potential target in the treatment of macrophage dysfunction. PMID:26354506

  12. ADAM22, a Kv1 channel-interacting protein, recruits membrane-associated guanylate kinases to juxtaparanodes of myelinated axons.

    PubMed

    Ogawa, Yasuhiro; Oses-Prieto, Juan; Kim, Moon Young; Horresh, Ido; Peles, Elior; Burlingame, Alma L; Trimmer, James S; Meijer, Dies; Rasband, Matthew N

    2010-01-20

    Clustered Kv1 K(+) channels regulate neuronal excitability at juxtaparanodes of myelinated axons, axon initial segments, and cerebellar basket cell terminals (BCTs). These channels are part of a larger protein complex that includes cell adhesion molecules and scaffolding proteins. To identify proteins that regulate assembly, clustering, and/or maintenance of axonal Kv1 channel protein complexes, we immunoprecipitated Kv1.2 alpha subunits, and then used mass spectrometry to identify interacting proteins. We found that a disintegrin and metalloproteinase 22 (ADAM22) is a component of the Kv1 channel complex and that ADAM22 coimmunoprecipitates Kv1.2 and the membrane-associated guanylate kinases (MAGUKs) PSD-93 and PSD-95. When coexpressed with MAGUKs in heterologous cells, ADAM22 and Kv1 channels are recruited into membrane surface clusters. However, coexpression of Kv1.2 with ADAM22 and MAGUKs does not alter channel properties. Among all the known Kv1 channel-interacting proteins, only ADAM22 is found at every site where Kv1 channels are clustered. Analysis of Caspr-null mice showed that, like other previously described juxtaparanodal proteins, disruption of the paranodal junction resulted in redistribution of ADAM22 into paranodal zones. Analysis of Caspr2-, PSD-93-, PSD-95-, and double PSD-93/PSD-95-null mice showed ADAM22 clustering at BCTs requires PSD-95, but ADAM22 clustering at juxtaparanodes requires neither PSD-93 nor PSD-95. In direct contrast, analysis of ADAM22-null mice demonstrated juxtaparanodal clustering of PSD-93 and PSD-95 requires ADAM22, whereas Kv1.2 and Caspr2 clustering is normal in ADAM22-null mice. Thus, ADAM22 is an axonal component of the Kv1 K(+) channel complex that recruits MAGUKs to juxtaparanodes. PMID:20089912

  13. Concerted Trafficking Regulation of Kv2.1 and KATP Channels by Leptin in Pancreatic β-Cells.

    PubMed

    Wu, Yi; Shyng, Show-Ling; Chen, Pei-Chun

    2015-12-11

    In pancreatic β-cells, voltage-gated potassium 2.1 (Kv2.1) channels are the dominant delayed rectifier potassium channels responsible for action potential repolarization. Here, we report that leptin, a hormone secreted by adipocytes known to inhibit insulin secretion, causes a transient increase in surface expression of Kv2.1 channels in rodent and human β-cells. The effect of leptin on Kv2.1 surface expression is mediated by the AMP-activated protein kinase (AMPK). Activation of AMPK mimics whereas inhibition of AMPK occludes the effect of leptin. Inhibition of Ca(2+)/calmodulin-dependent protein kinase kinase β, a known upstream kinase of AMPK, also blocks the effect of leptin. In addition, the cAMP-dependent protein kinase (PKA) is involved in Kv2.1 channel trafficking regulation. Inhibition of PKA prevents leptin or AMPK activators from increasing Kv2.1 channel density, whereas stimulation of PKA is sufficient to promote Kv2.1 channel surface expression. The increased Kv2.1 surface expression by leptin is dependent on actin depolymerization, and pharmacologically induced actin depolymerization is sufficient to enhance Kv2.1 surface expression. The signaling and cellular mechanisms underlying Kv2.1 channel trafficking regulation by leptin mirror those reported recently for ATP-sensitive potassium (KATP) channels, which are critical for coupling glucose stimulation with membrane depolarization. We show that the leptin-induced increase in surface KATP channels results in more hyperpolarized membrane potentials than control cells at stimulating glucose concentrations, and the increase in Kv2.1 channels leads to a more rapid repolarization of membrane potential in cells firing action potentials. This study supports a model in which leptin exerts concerted trafficking regulation of KATP and Kv2.1 channels to coordinately inhibit insulin secretion.

  14. Transmission electron microscopy of a model crystalline organic, theophylline

    NASA Astrophysics Data System (ADS)

    Cattle, J.; S'ari, M.; Hondow, N.; Abellán, P.; Brown, A. P.; Brydson, R. M. D.

    2015-10-01

    We report on the use of transmission electron microscopy (TEM) to analyse the diffraction patterns of the model crystalline organic theophylline to investigate beam damage in relation to changing accelerating voltage, sample temperature and TEM grid support films. We find that samples deposited on graphene film grids have the longest lifetimes when also held at -190 °C and imaged at 200 kV accelerating voltage. Finally, atomic lattice images are obtained in bright field STEM by working close to the estimated critical electron dose for theophylline.

  15. Structure-Activity Relationship Exploration of Kv1.3 Blockers Based on Diphenoxylate

    PubMed Central

    Nguyen, William; Howard, Brittany L.; Jenkins, David P.; Wulff, Heike; Thompson, Philip E.; Manallack, David T.

    2013-01-01

    Diphenoxylate, a well-known opioid agonist and anti-diarrhoeal agent, was recently found to block Kv1.3 potassium channels, which have been proposed as potential therapeutic targets for a range of autoimmune diseases. The molecular basis for this Kv1.3 blockade was assessed by the selective removal of functional groups from the structure of diphenoxylate as well as a number of other structural variations. Removal of the nitrile functional group and replacement of the C-4 piperidinyl substituents resulted in several compounds with submicromolar IC50 values. PMID:23084278

  16. 6. 6 kV/1. 5 kA-class superconducting fault current limiter development

    SciTech Connect

    Ito, D.; Yoneda, E.S.; Tsurunaga, K.; Tada, T. ); Hara, T.; Ohkuma, T.; Yamamoto, T. )

    1992-01-01

    This paper reports that the authors have developed and tested a 6.6 kV/1.5 kA-class fault current limiter wound with a 42-strand AC superconducting wire having ultra-fine MbTi filaments in a high resistivity matrix. In experiments, voltages up to 7.2 kV were applied to the limiter with phase angles of 0, 45, and 90 degrees. The limiter was able to limit the fault current to 1.8 kA successfully from the 55 kA short-circuit current that would flow in a circuit without limiter.

  17. Planning and installation of the 138 kV South Padre Island submarine cable

    SciTech Connect

    Cooper, J.H. ); Polasek, M.J. )

    1993-10-01

    This paper describes the planning, design and installation phases of a 138 kV submarine cable project which was recently completed by Central Power and Light (CPL) to improve the service reliability of South Padre Island and the town of Port Isabel. The project presented unique installation problems due to the shallow water depths combined with the necessity to minimize the environmental impact to sea grasses during the cable installation. This project resulted in the longest 138 kV extruded dielectric submarine cable circuit in the US.

  18. Development of 17 kV 4H-SiC PiN diode

    NASA Astrophysics Data System (ADS)

    Runhua, Huang; Yonghong, Tao; Ling, Wang; Gang, Chen; Song, Bai; Rui, Li; Yun, Li; Zhifei, Zhao

    2016-08-01

    The design, fabrication, and electrical characteristics of a 4H-SiC PiN diode with breakdown voltage higher than 17 kV are presented. The three-zone JTE has been used in the fabrication. Numerical simulations have been performed to optimize the parameters of the edge termination technique. The epilayer properties of the N-type are 175 μm with a doping of 2 × 1014 cm-3. With the three-zone JTE, a typical breakdown voltage of 17 kV has been achieved. Project supported by the National High Technology Research and Development Program of China (No. 2014AA041401).

  19. Development of 17 kV 4H-SiC PiN diode

    NASA Astrophysics Data System (ADS)

    Runhua, Huang; Yonghong, Tao; Ling, Wang; Gang, Chen; Song, Bai; Rui, Li; Yun, Li; Zhifei, Zhao

    2016-08-01

    The design, fabrication, and electrical characteristics of a 4H-SiC PiN diode with breakdown voltage higher than 17 kV are presented. The three-zone JTE has been used in the fabrication. Numerical simulations have been performed to optimize the parameters of the edge termination technique. The epilayer properties of the N-type are 175 μm with a doping of 2 × 1014 cm‑3. With the three-zone JTE, a typical breakdown voltage of 17 kV has been achieved. Project supported by the National High Technology Research and Development Program of China (No. 2014AA041401).

  20. Recent progress of the improved magnetically insulated transmission line oscillator.

    PubMed

    Fan, Yu-Wei; Zhong, Hui-Huang; Li, Zhi-Qiang; Shu, Ting; Zhang, Jian-De; Liu, Jin-Liang; Yang, Jian-Hua; Zhang, Jun; Yuan, Cheng-Wei; Luo, Ling

    2008-03-01

    The improved magnetically insulated transmission line oscillator (MILO) is a gigawatt-class L-band high power microwave tube driven by a 550 kV, 57 kA, 50 ns electron beam. It has allowed us to generate 2.4 GW pulse of 22 ns duration. The recent progress of the improved MILO is presented in this paper. First, a field shaper cathode is introduced into the improved MILO to avoid the cathode flares in the triple point region. The experimental results show that the cathode flares are avoided, so the lifetime of the velvet cathode is longer than that of the taper cathode. Furthermore, the shot-to-shot reproducibility is better than that of the taper cathode. Second, In order to prolong the pulse duration and increase the radiated microwave power, a self-built 600 kV, 10 Omega, 80 ns pulser: SPARK-03 is employed to drive the improved MILO. Simulation and experimental investigation are performed. In simulation, when the improved MILO is driven by a 600 kV, 57 kA electron beam, high-power microwave is generated with output power of 4.15 GW, frequency of 1.76 GHz, and relevant power conversion efficiency of 12.0%. In experiments, when the diode voltage is 550 kV and current is 54 kA, the measured results are that the radiated microwave power is above 3.1 GW, the pulse duration is above 40 ns, the microwave frequency is about 1.755 GHz, and the power conversion efficiency is about 10.4%.

  1. Electric power high-voltage transmission lines: Design options, cost, and electric and magnetic field levels

    SciTech Connect

    Stoffel, J.B.; Pentecost, E.D.; Roman, R.D.; Traczyk, P.A.

    1994-11-01

    This report provides background information about (1) the electric and magnetic fields (EMFs) of high-voltage transmission lines at typical voltages and line configurations and (2) typical transmission line costs to assist on alternatives in environmental documents. EMF strengths at 0 {+-} 200 ft from centerline were calculated for ac overhead lines, and for 345 and 230-kV ac underground line and for a {+-}450-kV dc overhead line. Compacting and height sensitivity factors were computed for the variation in EMFs when line conductors are moved closer or raised. Estimated costs for the lines are presented and discussed so that the impact of using alternative strategies for reducing EMF strengths and the implications of implementing the strategies can be better appreciated.

  2. Zika and Sexual Transmission

    MedlinePlus

    ... Address What's this? Submit What's this? Submit Button Zika and Sexual Transmission Language: English Español Português ... Healthcare Providers: Sexual Transmission of Zika Basics of Zika Virus and Sex Transmission Zika can be passed ...

  3. Molecular expression and pharmacological evidence for a functional role of kv7 channel subtypes in Guinea pig urinary bladder smooth muscle.

    PubMed

    Afeli, Serge A Y; Malysz, John; Petkov, Georgi V

    2013-01-01

    Voltage-gated Kv7 (KCNQ) channels are emerging as essential regulators of smooth muscle excitability and contractility. However, their physiological role in detrusor smooth muscle (DSM) remains to be elucidated. Here, we explored the molecular expression and function of Kv7 channel subtypes in guinea pig DSM by RT-PCR, qRT-PCR, immunohistochemistry, electrophysiology, and isometric tension recordings. In whole DSM tissue, mRNAs for all Kv7 channel subtypes were detected in a rank order: Kv7.1~Kv7.2Kv7.3~Kv7.5Kv7.4. In contrast, freshly-isolated DSM cells showed mRNA expression of: Kv7.1~Kv7.2Kv7.5Kv7.3~Kv7.4. Immunohistochemical confocal microscopy analyses of DSM, conducted by using co-labeling of Kv7 channel subtype-specific antibodies and α-smooth muscle actin, detected protein expression for all Kv7 channel subtypes, except for the Kv7.4, in DSM cells. L-364373 (R-L3), a Kv7.1 channel activator, and retigabine, a Kv7.2-7.5 channel activator, inhibited spontaneous phasic contractions and the 10-Hz electrical field stimulation (EFS)-induced contractions of DSM isolated strips. Linopiridine and XE991, two pan-Kv7 (effective at Kv7.1-Kv7.5 subtypes) channel inhibitors, had opposite effects increasing DSM spontaneous phasic and 10 Hz EFS-induced contractions. EFS-induced DSM contractions generated by a wide range of stimulation frequencies were decreased by L-364373 (10 µM) or retigabine (10 µM), and increased by XE991 (10 µM). Retigabine (10 µM) induced hyperpolarization and inhibited spontaneous action potentials in freshly-isolated DSM cells. In summary, Kv7 channel subtypes are expressed at mRNA and protein levels in guinea pig DSM cells. Their pharmacological modulation can control DSM contractility and excitability; therefore, Kv7 channel subtypes provide potential novel therapeutic targets for urinary bladder dysfunction.

  4. Physiological Role of Kv1.3 Channel in T Lymphocyte Cell Investigated Quantitatively by Kinetic Modeling

    PubMed Central

    Feng, Jing; Wang, Wei; Wu, Yingliang; Ding, Jiuping

    2014-01-01

    Kv1.3 channel is a delayed rectifier channel abundant in human T lymphocytes. Chronic inflammatory and autoimmune disorders lead to the over-expression of Kv1.3 in T cells. To quantitatively study the regulatory mechanism and physiological function of Kv1.3 in T cells, it is necessary to have a precise kinetic model of Kv1.3. In this study, we firstly established a kinetic model capable to precisely replicate all the kinetic features for Kv1.3 channels, and then constructed a T-cell model composed of ion channels including Ca2+-release activated calcium (CRAC) channel, intermediate K+ (IK) channel, TASK channel and Kv1.3 channel for quantitatively simulating the changes in membrane potentials and local Ca2+ signaling messengers during activation of T cells. Based on the experimental data from current-clamp recordings, we successfully demonstrated that Kv1.3 dominated the membrane potential of T cells to manipulate the Ca2+ influx via CRAC channel. Our results revealed that the deficient expression of Kv1.3 channel would cause the less Ca2+ signal, leading to the less efficiency in secretion. This was the first successful attempt to simulate membrane potential in non-excitable cells, which laid a solid basis for quantitatively studying the regulatory mechanism and physiological role of channels in non-excitable cells. PMID:24594979

  5. Silencing of Kv4.1 potassium channels inhibits cell proliferation of tumorigenic human mammary epithelial cells

    SciTech Connect

    Jang, Soo Hwa; Choi, Changsun; Hong, Seong-Geun; Yarishkin, Oleg V.; Bae, Young Min; Kim, Jae Gon; O'Grady, Scott M.; Kang, Kyung-Sun; Ryu, Pan Dong; Lee, So Yeong

    2009-06-26

    Potassium channel activity has been shown to facilitate cell proliferation in cancer cells. In the present study, the role of Kv4.1 channels in immortal and tumorigenic human mammary epithelial cells was investigated. Kv4.1 protein expression was positively correlated with tumorigenicity. Moreover, transfection with siRNAs targeting Kv4.1 mRNA suppressed proliferation of tumorigenic mammary epithelial cells. Experiments using mRNA isolated from human breast cancer tissues revealed that the level of Kv4.1 mRNA expression varied depending on the stage of the tumor. Kv4.1 protein expression increased during stages T2 and T3 compared to normal tissue. These results demonstrated that Kv4.1 plays a role in proliferation of tumorigenic human mammary epithelial cells. In addition, elevated Kv4.1 expression may be useful as a diagnostic marker for staging mammary tumors and selective blockers of Kv4.1 may serve to suppress tumor cell proliferation.

  6. Survey of Transmission Cost Allocation Methodologies for Regional Transmission Organizations

    SciTech Connect

    Fink, S.; Porter, K.; Mudd, C.; Rogers, J.

    2011-02-01

    The report presents transmission cost allocation methodologies for reliability transmission projects, generation interconnection, and economic transmission projects for all Regional Transmission Organizations.

  7. Economic Development from New Generation and Transmission in Wyoming and Colorado (Fact Sheet)

    SciTech Connect

    Not Available

    2013-03-01

    This report analyzes the potential economic impacts in Colorado and Wyoming of a 225 MW natural gas fired electricity generation facility and a 900 MW wind farm constructed in Wyoming as well as a 180 mile, 345 kV transmission line that runs from Wyoming to Colorado. This report and analysis is not a forecast, but rather an estimate of economic activity associated with a hypothetical scenario.

  8. Economic Development from New Generation and Transmission in Wyoming and Colorado

    SciTech Connect

    Keyser, D.; Lantz, E.

    2013-03-01

    This report analyzes the potential economic impacts in Colorado and Wyoming of a 225 MW natural gas fired electricity generation facility and a 900 MW wind farm constructed in Wyoming as well as a 180 mile, 345 kV transmission line that runs from Wyoming to Colorado. This report and analysis is not a forecast, but rather an estimate of economic activity associated with a hypothetical scenario.

  9. Epilepsy-causing mutations in Kv7.2 C-terminus affect binding and functional modulation by calmodulin.

    PubMed

    Ambrosino, Paolo; Alaimo, Alessandro; Bartollino, Silvia; Manocchio, Laura; De Maria, Michela; Mosca, Ilaria; Gomis-Perez, Carolina; Alberdi, Araitz; Scambia, Giovanni; Lesca, Gaetan; Villarroel, Alvaro; Taglialatela, Maurizio; Soldovieri, Maria Virginia

    2015-09-01

    Mutations in the KCNQ2 gene, encoding for voltage-gated Kv7.2K(+) channel subunits, are responsible for early-onset epileptic diseases with widely-diverging phenotypic presentation, ranging from Benign Familial Neonatal Seizures (BFNS) to epileptic encephalopathy. In the present study, Kv7.2 BFNS-causing mutations (W344R, L351F, L351V, Y362C, and R553Q) have been investigated for their ability to interfere with calmodulin (CaM) binding and CaM-induced channel regulation. To this aim, semi-quantitative (Far-Western blotting) and quantitative (Surface Plasmon Resonance and dansylated CaM fluorescence) biochemical assays have been performed to investigate the interaction of CaM with wild-type or mutant Kv7.2 C-terminal fragments encompassing the CaM-binding domain; in parallel, mutation-induced changes in CaM-dependent Kv7.2 or Kv7.2/Kv7.3 current regulation were investigated by patch-clamp recordings in Chinese Hamster Ovary (CHO) cells co-expressing Kv7.2 or Kv7.2/Kv7.3 channels and CaM or CaM1234 (a CaM isoform unable to bind Ca(2+)). The results obtained suggest that each BFNS-causing mutation prompts specific biochemical and/or functional consequences; these range from slight alterations in CaM affinity which did not translate into functional changes (L351V), to a significant reduction in the affinity and functional modulation by CaM (L351F, Y362C or R553Q), to a complete functional loss without significant alteration in CaM affinity (W344R). CaM overexpression increased Kv7.2 and Kv7.2/Kv7.3 current levels, and partially (R553Q) or fully (L351F) restored normal channel function, providing a rationale pathogenetic mechanism for mutation-induced channel dysfunction in BFNS, and highlighting the potentiation of CaM-dependent Kv7.2 modulation as a potential therapeutic approach for Kv7.2-related epilepsies.

  10. 75 FR 63141 - Apalachicola National Forest; Florida; City of Tallahassee 230kV Southwestern Transmission Line

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-14

    ... FURTHER INFORMATION CONTACT: Harold Shenk, U.S. Forest Service, 57 Taff Drive, Crawfordville, FL 32327... Federal Information Relay Service (FIRS) at 1-800-877-8339 between 8 a.m. and 8 p.m., Eastern Time, Monday through Friday. SUPPLEMENTARY INFORMATION: Purpose and Need for Action The North American...

  11. 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

    ... Register at 73 FR 41312 a Notice of Intent to prepare an EIS for the proposed Project. On March 3, 2010... Federal Register at 75 FR 9573. The U.S. Environmental Protection Agency acknowledged receipt of the Draft... Project in the Federal Register on September 15, 2010 at 75 FR 56051. The U.S. Environmental...

  12. 75 FR 32357 - Gallatin National Forest; Montana; Jack Rabbit to Big Sky Meadow Village 161 kV Transmission Line...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-08

    ... among the fastest growing areas within NorthWestern Energy's service territory. NorthWestern Energy is... area. As the Big Sky area continues to grow, this situation will worsen. These reliability shortfalls... status plants and animals, invasive weeds, snag habitat) Water resources and wetlands Road blockages...

  13. 76 FR 19744 - Final Tropic to Hatch 138 kV Transmission Line Project Environmental Impact Statement and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-08

    ... Policy and Management Act of 1976, as amended, the Forest Service (FS), with the Bureau of Land..., Kanab, UT; Utah State Office, 440 W 200 S, Salt Lake City, UT. Interested persons may also download and/or review the FEIS/PMPA on the Internet at http://fs.usda.gov/goto/dixie/projects . All...

  14. A kernel-based method for markerless tumor tracking in kV fluoroscopic images

    NASA Astrophysics Data System (ADS)

    Zhang, Xiaoyong; Homma, Noriyasu; Ichiji, Kei; Abe, Makoto; Sugita, Norihiro; Takai, Yoshihiro; Narita, Yuichiro; Yoshizawa, Makoto

    2014-09-01

    Markerless tracking of respiration-induced tumor motion in kilo-voltage (kV) fluoroscopic image sequence is still a challenging task in real time image-guided radiation therapy (IGRT). Most of existing markerless tracking methods are based on a template matching technique or its extensions that are frequently sensitive to non-rigid tumor deformation and involve expensive computation. This paper presents a kernel-based method that is capable of tracking tumor motion in kV fluoroscopic image sequence with robust performance and low computational cost. The proposed tracking system consists of the following three steps. To enhance the contrast of kV fluoroscopic image, we firstly utilize a histogram equalization to transform the intensities of original images to a wider dynamical intensity range. A tumor target in the first frame is then represented by using a histogram-based feature vector. Subsequently, the target tracking is then formulated by maximizing a Bhattacharyya coefficient that measures the similarity between the tumor target and its candidates in the subsequent frames. The numerical solution for maximizing the Bhattacharyya coefficient is performed by a mean-shift algorithm. The proposed method was evaluated by using four clinical kV fluoroscopic image sequences. For comparison, we also implement four conventional template matching-based methods and compare their performance with our proposed method in terms of the tracking accuracy and computational cost. Experimental results demonstrated that the proposed method is superior to conventional template matching-based methods.

  15. Complete Genome Sequence of Murine Pneumotropic Virus (Polyomaviridae) Clone pKV(37-1)

    PubMed Central

    Libbey, Jane E.

    2016-01-01

    The murine pneumotropic virus genome encoded by the pKV(37-1) clone was sequenced to completion. The regulatory region harbored a mutation not previously reported. The protein coding regions (large and small T antigens, viral proteins 1 to 3) showed multiple regions of high amino acid identity to the human, simian, and bovine polyomaviruses. PMID:27198030

  16. Complete Genome Sequence of Murine Pneumotropic Virus (Polyomaviridae) Clone pKV(37-1).

    PubMed

    Libbey, Jane E; Fujinami, Robert S

    2016-01-01

    The murine pneumotropic virus genome encoded by the pKV(37-1) clone was sequenced to completion. The regulatory region harbored a mutation not previously reported. The protein coding regions (large and small T antigens, viral proteins 1 to 3) showed multiple regions of high amino acid identity to the human, simian, and bovine polyomaviruses. PMID:27198030

  17. Field evaluation of 69-kV outdoor Polysil insulators. Final report

    SciTech Connect

    Richenbacher, A.G.

    1985-03-01

    After three years of exposure to widely varying climates and environments, Polysil (polymer concrete) 69-kV post-type insulators are still performing satisfactorily. In all test situations, Polysil insulators performed as well as - sometimes even surpassed - their porcelain counterparts. They also demonstrated potential for substantially reducing insulator costs.

  18. Pivoting between calmodulin lobes triggered by calcium in the Kv7.2/calmodulin complex.

    PubMed

    Alaimo, Alessandro; Alberdi, Araitz; Gomis-Perez, Carolina; Fernández-Orth, Juncal; Bernardo-Seisdedos, Ganeko; Malo, Covadonga; Millet, Oscar; Areso, Pilar; Villarroel, Alvaro

    2014-01-01

    Kv7.2 (KCNQ2) is the principal molecular component of the slow voltage gated M-channel, which strongly influences neuronal excitability. Calmodulin (CaM) binds to two intracellular C-terminal segments of Kv7.2 channels, helices A and B, and it is required for exit from the endoplasmic reticulum. However, the molecular mechanisms by which CaM controls channel trafficking are currently unknown. Here we used two complementary approaches to explore the molecular events underlying the association between CaM and Kv7.2 and their regulation by Ca(2+). First, we performed a fluorometric assay using dansylated calmodulin (D-CaM) to characterize the interaction of its individual lobes to the Kv7.2 CaM binding site (Q2AB). Second, we explored the association of Q2AB with CaM by NMR spectroscopy, using (15)N-labeled CaM as a reporter. The combined data highlight the interdependency of the N- and C-lobes of CaM in the interaction with Q2AB, suggesting that when CaM binds Ca(2+) the binding interface pivots between the N-lobe whose interactions are dominated by helix B and the C-lobe where the predominant interaction is with helix A. In addition, Ca(2+) makes CaM binding to Q2AB more difficult and, reciprocally, the channel weakens the association of CaM with Ca(2+).

  19. Pivoting between Calmodulin Lobes Triggered by Calcium in the Kv7.2/Calmodulin Complex

    PubMed Central

    Alaimo, Alessandro; Alberdi, Araitz; Gomis-Perez, Carolina; Fernández-Orth, Juncal; Bernardo-Seisdedos, Ganeko; Malo, Covadonga; Millet, Oscar; Areso, Pilar; Villarroel, Alvaro

    2014-01-01

    Kv7.2 (KCNQ2) is the principal molecular component of the slow voltage gated M-channel, which strongly influences neuronal excitability. Calmodulin (CaM) binds to two intracellular C-terminal segments of Kv7.2 channels, helices A and B, and it is required for exit from the endoplasmic reticulum. However, the molecular mechanisms by which CaM controls channel trafficking are currently unknown. Here we used two complementary approaches to explore the molecular events underlying the association between CaM and Kv7.2 and their regulation by Ca2+. First, we performed a fluorometric assay using dansylated calmodulin (D-CaM) to characterize the interaction of its individual lobes to the Kv7.2 CaM binding site (Q2AB). Second, we explored the association of Q2AB with CaM by NMR spectroscopy, using 15N-labeled CaM as a reporter. The combined data highlight the interdependency of the N- and C-lobes of CaM in the interaction with Q2AB, suggesting that when CaM binds Ca2+ the binding interface pivots between the N-lobe whose interactions are dominated by helix B and the C-lobe where the predominant interaction is with helix A. In addition, Ca2+ makes CaM binding to Q2AB more difficult and, reciprocally, the channel weakens the association of CaM with Ca2+. PMID:24489773

  20. 8. VIEW OF 100 kV SWITCHYARD. TELEPHONE BOOTH AND THREESTALL ...

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

    8. VIEW OF 100 kV SWITCHYARD. TELEPHONE BOOTH AND THREE-STALL GARAGE. VIEW TO SOUTHWEST. - Rainbow Hydroelectric Facility, On north bank of Missouri River 2 miles Northeast of Great Falls, & end of Rainbow Dam Road, Great Falls, Cascade County, MT

  1. Progress of 275 kV-3 kA YBCO HTS cable

    NASA Astrophysics Data System (ADS)

    Yagi, M.; Mukoyama, S.; Amemiya, N.; Ishiyama, A.; Wang, X.; Aoki, Y.; Saito, T.; Ohkuma, T.; Maruyama, O.

    2011-11-01

    A 275 kV-3 kA high temperature superconducting (HTS) cable has been developed in the Materials & Power Applications of Coated Conductors (M-PACC) project. AC loss reduction of a two-layer HTS conductor was undertaken by removing the edges of YBCO tapes with low critical current density. The HTS conductor using these tapes was fabricated, and low loss of 0.235 W/m at 3 kA rms was achieved. The 275 kV-3 kA cable was designed, and the 2 m model cables were fabricated. This cable had 325 mm 2 copper stranded former inside the HTS conductor and a 310 mm 2 copper shield layer on the HTS shield layer for over-current protection. These cables withstood an over-current of 63.0 kA for 0.6 s, which is the worst situation for 275 kV systems. The partial discharge (PD) and V- t characteristics of a liquid nitrogen (LN 2)/polypropylene (PP) laminated paper composite insulation system have been integrated into the design of the insulation for the 275 kV cable. The results revealed that the PD inception stress (PDIE) did not depend on the insulation thickness, and that lifetime indices of V- t characteristics at PD inception were as high as about 80-100.

  2. Kv4 channel blockade reduces motor and neuropsychiatric symptoms in rodent models of Parkinson's disease.

    PubMed

    Aidi-Knani, Sabrine; Regaya, Imed; Amalric, Marianne; Mourre, Christiane

    2015-02-01

    The striatum, a major input structure of basal ganglia, integrates glutamatergic cortical and thalamic inputs to control psychomotor behaviors. Nigrostriatal dopamine (DA) neurodegeneration in Parkinson's disease causes a loss of spinal and glutamatergic synapses in the striatal medium spiny neurons (MSNs). Adaptive responses, a form of homeostatic plasticity, to these changes are caused by a decrease in a potassium Kv4 channel-dependent inactivating A-type potassium (KIA) current that increases the intrinsic excitability of MSNs. Nevertheless, the functional outcome of these compensatory mechanisms does not allow adequate behavioral recovery in vivo. We thus addressed the question of whether further blockade of Kv4 activity could enhance the striatal responsiveness of MSNs to DA depletion and restore normal function in vivo. To test this hypothesis, we examined the effects of a selective blocker of Kv4 channels, AmmTX3, on the motor, cognitive, and emotional symptoms produced by 6-hydroxydopamine lesions of the nigrostriatal DA pathway in rats. Striatal infusion of AmmTX3 (0.2-0.4 μg) reduced motor deficits, decreased anxiety, and restored short-term social and spatial memories. These results underlie the importance of Kv4 channels as players in the homeostatic responses, and, more importantly, provide a potential target for adjunctive therapies for Parkinson's disease. PMID:25356731

  3. Design and performance of a 30 KV electron gun with ten independent cathodes & a magnetic lens.

    SciTech Connect

    Rudys, Joseph Matthew; Reed, Kim Warren

    2006-08-01

    Measurements on a 30 kV electron gun with ten independent cathodes, operating in a 6.5 Tesla (T) magnetic field are presented. An earlier paper covered the design of this electron gun [1]. Experimental results are compared to model predictions. Beam current is compared to theoretical space charge limited flow.

  4. Kv4 channel blockade reduces motor and neuropsychiatric symptoms in rodent models of Parkinson's disease.

    PubMed

    Aidi-Knani, Sabrine; Regaya, Imed; Amalric, Marianne; Mourre, Christiane

    2015-02-01

    The striatum, a major input structure of basal ganglia, integrates glutamatergic cortical and thalamic inputs to control psychomotor behaviors. Nigrostriatal dopamine (DA) neurodegeneration in Parkinson's disease causes a loss of spinal and glutamatergic synapses in the striatal medium spiny neurons (MSNs). Adaptive responses, a form of homeostatic plasticity, to these changes are caused by a decrease in a potassium Kv4 channel-dependent inactivating A-type potassium (KIA) current that increases the intrinsic excitability of MSNs. Nevertheless, the functional outcome of these compensatory mechanisms does not allow adequate behavioral recovery in vivo. We thus addressed the question of whether further blockade of Kv4 activity could enhance the striatal responsiveness of MSNs to DA depletion and restore normal function in vivo. To test this hypothesis, we examined the effects of a selective blocker of Kv4 channels, AmmTX3, on the motor, cognitive, and emotional symptoms produced by 6-hydroxydopamine lesions of the nigrostriatal DA pathway in rats. Striatal infusion of AmmTX3 (0.2-0.4 μg) reduced motor deficits, decreased anxiety, and restored short-term social and spatial memories. These results underlie the importance of Kv4 channels as players in the homeostatic responses, and, more importantly, provide a potential target for adjunctive therapies for Parkinson's disease.

  5. Design and development of a 5 kV isolated solid state switch

    NASA Technical Reports Server (NTRS)

    Holbrook, R. J.; Scapple, R. Y.; Keister, F. Z.; Gooder, S. T.

    1975-01-01

    A unique microcircuit intended for use as a shorting switch for large extraterrestrial solar cell arrays is described. The packaging design for the 5 kV isolated hybrid switch is different from most hybrid microcircuits in that it utilizes a compartmentalized plastic case (a portion of which is encapsulated), is not hermetic, and is designed for high voltage operation.

  6. Kv4.2 Mediates Histamine Modulation of Preoptic Neuron Activity and Body Temperature

    PubMed Central

    Sethi, Jasmine; Sanchez-Alavez, Manuel; Tabarean, Iustin V.

    2011-01-01

    Histamine regulates arousal, circadian rhythms, and thermoregulation. Activation of H3 histamine receptors expressed by preoptic GABAergic neurons results in a decrease of their firing rate and hyperthermia. Here we report that an increase in the A-type K+ current in preoptic GABAergic neurons in response to activation of H3 histamine receptors results in decreased firing rate and hyperthermia in mice. The Kv4.2 subunit is required for these actions in spite of the fact that Kv4.2−/− preoptic GABAergic neurons display A-type currents and firing characteristics similar to those of wild-type neurons. This electrical remodeling is achieved by robust upregulation of the expression of the Kv4.1 subunit and of a delayed rectifier current. Dynamic clamp experiments indicate that enhancement of the A-type current by a similar amount to that induced by histamine is sufficient to mimic its robust effect on firing rates. These data indicate a central role played by the Kv4.2 subunit in histamine regulation of body temperature and its interaction with pERK1/2 downstream of the H3 receptor. We also reveal that this pathway provides a mechanism for selective modulation of body temperature at the beginning of the active phase of the circadian cycle. PMID:22220205

  7. Analysis on heat loss characteristics of a 10 kV HTS power substation

    NASA Astrophysics Data System (ADS)

    Teng, Yuping; Dai, Shaotao; Song, Naihao; Zhang, Jingye; Gao, Zhiyuan; Zhu, Zhiqin; Zhou, Weiwei; Wei, Zhourong; Lin, Liangzhen; Xiao, Liye

    2014-09-01

    A 10 kV High Temperature Superconducting power substation (10 kV HTS substation), supported by Chinese State 863 projects, was developed and has been running to supply power for several factories for more than two years at an industrial park of Baiyin, Gansu province in Northwest China. The system of the 10 kV HTS substation compositions, including a HTS cable, a HTS transformer, a SFCL, and a SMES, are introduced. The SMES works at liquid helium temperature and the other three apparatus operates under liquid nitrogen condition. There are mainly four types of heat losses existing in each HTS apparatus of the 10 kV HTS substation, including AC loss, Joule heat loss, conductive heat, and leak-in heat from cryostat. A small quantity of AC loss still exists due to the harmonic component of the current when it carries DC for HTS apparatus. The principle and basis for analysis of the heat losses are introduced and the total heat loss of each apparatus are calculated or estimated, which agree well with the test result. The analysis and result presented are of importance for the design of the refrigeration system.

  8. Supplement Analysis for the Transmission System Vegetation Management Program FEIS (DOE/EIS-0285/SA-34)

    SciTech Connect

    Stratton, Elaine

    2001-12-03

    Vegetation Management along the McNary-Ross Transmission Line ROW between 152/3+2120 to 153/4. The line is 345 kV Single Circuit Transmission Line (project includes adjacent N. Bonneville-Ross 230 kV Single Circuit Transmission Line) having a combined easement width of 300 feet. The proposed work will be accomplished in the indicated sections of the transmission line corridor. BPA proposes to clear unwanted vegetation in the rights-of-ways and around tower structures that may impede the operation and maintenance of the subject transmission line. Also, access road clearing will be conducted. All work will be in accordance with the National Electrical Safety Code and BPA standards. BPA plans to conduct vegetation control with the goal of removing tall growing vegetation that is currently or will soon be a hazard to the transmission line. BPA’s overall goal is to have low-growing plant communities along the rights-of-way to control the development of potentially threatening vegetation.

  9. Critical contribution of KV1 channels to the regulation of coronary blood flow.

    PubMed

    Goodwill, Adam G; Noblet, Jillian N; Sassoon, Daniel; Fu, Lijuan; Kassab, Ghassan S; Schepers, Luke; Herring, B Paul; Rottgen, Trey S; Tune, Johnathan D; Dick, Gregory M

    2016-09-01

    Ion channels in smooth muscle control coronary vascular tone, but the identity of the potassium channels involved requires further investigation. The purpose of this study was to evaluate the functional role of KV1 channels on porcine coronary blood flow using the selective antagonist correolide. KV1 channel gene transcripts were found in porcine coronary arteries, with KCNA5 (encoding KV1.5) being most abundant (P < 0.001). Immunohistochemical staining demonstrated KV1.5 protein in the vascular smooth muscle layer of both porcine and human coronary arteries, including microvessels. Whole-cell patch-clamp experiments demonstrated significant correolide-sensitive (1-10 µM) current in coronary smooth muscle. In vivo studies included direct intracoronary infusion of vehicle or correolide into a pressure-clamped left anterior descending artery of healthy swine (n = 5 in each group) with simultaneous measurement of coronary blood flow. Intracoronary correolide (~0.3-3 µM targeted plasma concentration) had no effect on heart rate or systemic pressure, but reduced coronary blood flow in a dose-dependent manner (P < 0.05). Dobutamine (0.3-10 µg/kg/min) elicited coronary metabolic vasodilation and intracoronary correolide (3 µM) significantly reduced coronary blood flow at any given level of myocardial oxygen consumption (P < 0.001). Coronary artery occlusions (15 s) elicited reactive hyperemia and correolide (3 µM) reduced the flow volume repayment by approximately 30 % (P < 0.05). Taken together, these data support a major role for KV1 channels in modulating baseline coronary vascular tone and, perhaps, vasodilation in response to increased metabolism and transient ischemia. PMID:27496159

  10. Encephalitis and antibodies to DPPX, a subunit of Kv4.2 potassium channels

    PubMed Central

    Boronat, Anna; Gelfand, Jeffrey M.; Gresa-Arribas, Nuria; Jeong, Hyo-Young; Walsh, Michael; Roberts, Kirk; Martinez-Hernandez, Eugenia; Rosenfeld, Myrna R.; Balice-Gordon, Rita; Graus, Francesc; Rudy, Bernardo; Dalmau, Josep

    2012-01-01

    Objective To report a novel cell-surface autoantigen of encephalitis that is a critical regulatory subunit of the Kv4.2 potassium channels. Methods Four patients with encephalitis of unclear etiology and antibodies with a similar pattern of neuropil brain immunostaining were selected for autoantigen characterization. Techniques included immunoprecipitation, mass spectrometry, cell-base experiments with Kv4.2 and several dipeptidyl-peptidase-like protein-6 (DPPX) plasmid constructs, and comparative brain immunostaining of wild-type and DPPX-null mice. Results Immunoprecipitation studies identified DPPX as the target autoantigen. A cell based assay confirmed that all 4 patients, but not 210 controls, had DPPX antibodies. Symptoms included agitation, confusion, myoclonus, tremor, and seizures (one case with prominent startle response). All patients had pleocytosis, and three had severe prodromal diarrhea of unknown etiology. Given that DPPX “tunes up” the Kv4.2 potassium channels (involved in somatodendritic signal integration and attenuation of dendritic backpropagation of action potentials), we determined the epitope distribution in DPPX, DPP10 (a protein homologous to DPPX) and Kv4.2. Patients’ antibodies were found specific for DPPX, without reacting with DPP10 or Kv4.2. The unexplained diarrhea led to demonstrate a robust expression of DPPX in the myenteric plexus, which strongly reacted with patients’ antibodies. The course of neuropsychiatric symptoms was prolonged and often associated with relapses while decreasing immunotherapy. Long-term follow-up showed substantial improvement in 3 patients (1 is lost to follow-up). Interpretation Antibodies to DPPX associate with a protracted encephalitis characterized by CNS hyperexcitability (agitation, myoclonus, tremor, seizures), pleocytosis, and frequent diarrhea at symptom onset. The disorder is potentially treatable with immunotherapy. PMID:23225603

  11. Myricetin inhibits Kv1.5 channels in HEK293 cells.

    PubMed

    Ou, Xianhong; Bin, Xiaohong; Wang, Luzhen; Li, Miaoling; Yang, Yan; Fan, Xinrong; Zeng, Xiaorong

    2016-02-01

    Myricetin (Myr) is a flavonoid that exerts anti-arrhythmic effects. However, its potential effects on ion channels have remained elusive. The aim of the present study was to investigate the effects of Myr on Kv1.5 channels in HEK293 cells. The current of Kv1.5 channels (Ikur) in HEK293 cells was recorded using the whole-cell patch-clamp technique and the expression of the Kv1.5 protein was measured using western blot analysis 24 h after treatment with Myr. The results showed that 5 µM Myr significantly reduced Ikur from 215.04 ± 40.59 to 77.72 ± 17.94 pA/pF (P<0.05; n=5). Myr increased the current suppression from 0 to 0.31 ± 0.12 and 0.55 ± 0.11 over 5 or 20 min, respectively. In addition, Ikur decreased from 376.23 ± 1.30 to 270.19 ± 4.28 pA/pF when the frequency was increased from 0.5 to 4 Hz in HEK293 cells treated with 10 µM Myr for 5 min. Furthermore, Myr reduced hKv1.5 protein expression in a dose-dependent manner. These results demonstrated that Myr inhibited Ikur and the expression of hKv1.5 in HEK293 cells in a dose-, time- and frequency-dependent manner. These observations partly explained the mechanisms by which Myr exerts anti-arrhythmic effect.

  12. Increasing the molecular contacts between maurotoxin and Kv1.2 channel augments ligand affinity.

    PubMed

    M'Barek, Sarrah; Chagot, Benjamin; Andreotti, Nicolas; Visan, Violeta; Mansuelle, Pascal; Grissmer, Stephan; Marrakchi, Mohamed; El Ayeb, Mohamed; Sampieri, François; Darbon, Hervé; Fajloun, Ziad; De Waard, Michel; Sabatier, Jean-Marc

    2005-08-15

    Scorpion toxins interact with their target ion channels through multiple molecular contacts. Because a "gain of function" approach has never been described to evaluate the importance of the molecular contacts in defining toxin affinity, we experimentally examined whether increasing the molecular contacts between a toxin and an ion channel directly impacts toxin affinity. For this purpose, we focused on two scorpion peptides, the well-characterized maurotoxin with its variant Pi1-like disulfide bridging (MTX(Pi1)), used as a molecular template, and butantoxin (BuTX), used as an N-terminal domain provider. BuTX is found to be 60-fold less potent than MTX(Pi1) in blocking Kv1.2 (IC(50) values of 165 nM for BuTX versus 2.8 nM for MTX(Pi1)). Removal of its N-terminal domain (nine residues) further decreases BuTX affinity for Kv1.2 by 5.6-fold, which is in agreement with docking simulation data showing the importance of this domain in BuTX-Kv1.2 interaction. Transfer of the BuTX N-terminal domain to MTX(Pi1) results in a chimera with five disulfide bridges (BuTX-MTX(Pi1)) that exhibits 22-fold greater affinity for Kv1.2 than MTX(Pi1) itself, in spite of the lower affinity of BuTX as compared to MTX(Pi1). Docking experiments performed with the 3-D structure of BuTX-MTX(Pi1) in solution, as solved by (1)H-NMR, reveal that the N-terminal domain of BuTX participates in the increased affinity for Kv1.2 through additional molecular contacts. Altogether, the data indicate that acting on molecular contacts between a toxin and a channel is an efficient strategy to modulate toxin affinity.

  13. Combined kV and MV imaging for real-time tracking of implanted fiducial markers.

    PubMed

    Wiersma, R D; Mao, Weihua; Xing, L

    2008-04-01

    In the presence of intrafraction organ motion, target localization uncertainty can greatly hamper the advantage of highly conformal dose techniques such as intensity modulated radiation therapy (IMRT). To minimize the adverse dosimetric effect caused by tumor motion, a real-time knowledge of the tumor position is required throughout the beam delivery process. The recent integration of onboard kV diagnostic imaging together with MV electronic portal imaging devices on linear accelerators can allow for real-time three-dimensional (3D) tumor position monitoring during a treatment delivery. The aim of this study is to demonstrate a near real-time 3D internal fiducial tracking system based on the combined use of kV and MV imaging. A commercially available radiotherapy system equipped with both kV and MV imaging systems was used in this work. A hardware video frame grabber was used to capture both kV and MV video streams simultaneously through independent video channels at 30 frames per second. The fiducial locations were extracted from the kV and MV images using a software tool. The geometric tracking capabilities of the system were evaluated using a pelvic phantom with embedded fiducials placed on a moveable stage. The maximum tracking speed of the kV/MV system is approximately 9 Hz, which is primarily limited by the frame rate of the MV imager. The geometric accuracy of the system is found to be on the order of less than 1 mm in all three spatial dimensions. The technique requires minimal hardware modification and is potentially useful for image-guided radiation therapy systems.

  14. Kv4 Channels Underlie the Subthreshold-Operating A-type K-current in Nociceptive Dorsal Root Ganglion Neurons.

    PubMed

    Phuket, Thanawath Ratanadilok Na; Covarrubias, Manuel

    2009-01-01

    The dorsal root ganglion (DRG) contains heterogeneous populations of sensory neurons including primary nociceptive neurons and C-fibers implicated in pain signaling. Recent studies have demonstrated DRG hyperexcitability associated with downregulation of A-type K(+) channels; however, the molecular correlate of the corresponding A-type K(+) current (I(A)) has remained hypothetical. Kv4 channels may underlie the I(A) in DRG neurons. We combined electrophysiology, molecular biology (Whole-Tissue and Single-Cell RT-PCR) and immunohistochemistry to investigate the molecular basis of the I(A) in acutely dissociated DRG neurons from 7- to 8-day-old rats. Whole-cell recordings demonstrate a robust tetraethylammonium-resistant (20 mM) and 4-aminopyridine-sensitive (5 mM) I(A). Matching Kv4 channel properties, activation and inactivation of this I(A) occur in the subthreshold range of membrane potentials and the rate of recovery from inactivation is rapid and voltage-dependent. Among Kv4 transcripts, the DRG expresses significant levels of Kv4.1 and Kv4.3 mRNAs. Also, single small-medium diameter DRG neurons ( approximately 30 mum) exhibit correlated frequent expression of mRNAs encoding Kv4.1 and Nav1.8, a known nociceptor marker. In contrast, the expressions of Kv1.4 and Kv4.2 mRNAs at the whole-tissue and single-cell levels are relatively low and infrequent. Kv4 protein expression in nociceptive DRG neurons was confirmed by immunohistochemistry, which demonstrates colocalization of Kv4.3 and Nav1.8, and negligible expression of Kv4.2. Furthermore, specific dominant-negative suppression and overexpression strategies confirmed the contribution of Kv4 channels to I(A) in DRG neurons. Contrasting the expression patterns of Kv4 channels in the central and peripheral nervous systems, we discuss possible functional roles of these channels in primary sensory neurons. PMID:19668710

  15. Differential cycling rates of Kv4.2 channels in proximal and distal dendrites of hippocampal CA1 pyramidal neurons

    PubMed Central

    Nestor, Michael W.; Hoffman, Dax A.

    2010-01-01

    The heterogeneous expression of voltage-gated channels in dendrites suggests that neurons perform local microdomain computations at different regions. It has been shown that A-type K+ channels have a non-uniform distribution along the primary apical dendrite in CA1 pyramidal neurons, increasing with distance from the soma. Kv4.2 channels, which are responsible for the somatodendritic A-type K+ current in CA1 pyramidal neurons, shape local synaptic input and regulate the back-propagation of APs into dendrites. Experiments were performed to test the hypothesis that Kv4.2 channels are differentially trafficked at different regions along the apical dendrite during basal activity and upon stimulation in CA1 neurons. Proximal (50–150 µm from the soma, primary and oblique) and distal (>200 µm) apical dendrites were selected. The fluorescence recovery after photobleaching (FRAP) technique was used to measure basal cycling rates of EGFP-tagged Kv4.2 (Kv4.2g). We found that the cycling rate of Kv4.2 channels was one order of magnitude slower at both primary and oblique dendrites between 50–150 µm from the soma. Kv4.2 channel cycling increased significantly at 200–250 µm from the soma. Expression of a Kv4.2 mutant lacking a phosphorylation site for protein kinase-A (Kv4.2gS552A) abolished this distance-dependent change in channel cycling; demonstrating that phosphorylation by PKA underlies the increased mobility in distal dendrites. Neuronal stimulation by α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) treatment increased cycling of Kv4.2 channels significantly at distal sites only. This activity-dependent increase in Kv4.2 cycling at distal dendrites was blocked by expression of Kv4.2gS552A. These results indicate that distance-dependent Kv4.2 mobility is regulated by activity-dependent phosphorylation of Kv4.2 by PKA. PMID:21472817

  16. Supplement Analysis for the Transmission System Vegetation Management Program FEIS (DOE/EIS-0285/SA-57)

    SciTech Connect

    Stratton, Elaine

    2002-04-10

    Vegetation Management along the Trojan-Allston Transmission Lines 1 & 2 ROW between 1/1 and 9/1. The lines are 230 kV Single Circuit Transmission Lines having an easement width of 125 feet. The proposed work will be accomplished in the indicated sections of the transmission line corridor. BPA proposes to clear unwanted vegetation in the rights-of-ways and around tower structures that may impede the operation and maintenance of the subject transmission line. All work will be in accordance with the National Electrical Safety Code and BPA standards. BPA plans to conduct vegetation control with the goal of removing tall growing vegetation that is currently or will soon be a hazard to the transmission line. BPA’s overall goal is to have low-growing plant communities along the rights-of-way to control the development of potentially threatening vegetation.

  17. Supplement Analysis for the Transmission System Vegetation Management Program FEIS (DOE/EIS-0285/SA-100)

    SciTech Connect

    Rosales, Michael A.

    2002-08-15

    Vegetation Management along the Libby-Conkelly, 1/2 to 26/4 Transmission Line ROW. The line is a 230kV Double Circuit Transmission Line having an easement width of 125 feet to 250 feet. The proposed work will be accomplished in the indicated sections of the transmission line corridor. BPA proposes to clear unwanted vegetation in the rights-of-ways and around tower structures that may impede the operation and maintenance of the subject transmission line. All work will be in accordance with the National Electrical Safety Code and BPA standards. BPA plans to conduct vegetation control with the goal of removing tall growing vegetation that is currently or will soon be a hazard to the transmission line. BPA’s overall goal is to have low-growing plant communities along the rights-of-way to control the development of potentially threatening vegetation.

  18. Supplement Analysis for the Transmission System Vegetation Management Program FEIS (DOE/EIS-0285/SA-20)

    SciTech Connect

    Hutchinson, Ken

    2001-08-02

    Vegetation Management along the McNary-Ross 161/1 to 166/5+346 Transmission Line ROW. The line is a 345kV Single Circuit Transmission Line having an easement width of 175 feet. The proposed work will be accomplished in the indicated sections of the transmission line corridor. BPA proposes to clear unwanted vegetation in the rights-of-ways and around tower structures that may impede the operation and maintenance of the subject transmission line. Also, access road clearing will be conducted. All work will be in accordance with the National Electrical Safety Code and BPA standards. BPA plans to conduct vegetation control with the goal of removing tall growing vegetation that is currently or will soon be a hazard to the transmission line. BPA’s overall goal is to have low-growing plant communities along the rights-of-way to control the development of potentially threatening vegetation.

  19. Supplement Analysis for the Transmission System Vegetation Management Program FEIS (DOE/EIS-0285/SA-137- Chemawa-Salem 1&2)

    SciTech Connect

    Sherer, Brett M.

    2003-04-01

    Vegetation Management for the Chemawa-Salem #1 115 kV and #2 230 kV transmission lines from Chemawa Substation to Salem Substation. BPA proposes to remove unwanted vegetation along the right-of-way, access roads, switch platforms, and around tower structures of the subject transmission line corridor that may impede the operation and maintenance of the identified transmission lines. BPA plans to conduct vegetation control with the goal of removing tall growing vegetation that is currently or will soon be a hazard to the transmission line. BPA’s overall goal is to have lowgrowing plant communities along the rights-of-way to control the development of potentially threatening vegetation.

  20. HTS DC Transmission Line for Megalopolis Grid Development

    NASA Astrophysics Data System (ADS)

    Kopylov, S.; Sytnikov, V.; Bemert, S.; Ivanov, Yu; Krivetskiy, I.; Romashov, M.; Shakaryan, Yu; Keilin, V.; Shikov, A.; Patrikeev, V.; Lobyntsev, V.; Shcherbakov, V.

    2014-05-01

    Using of HTS AC and DC cables in electric power grids allows increasing of the transferred power, losses diminishing, decreasing of exclusion zone areas, the enhancement of the environmental conditions and fire/explosion safety of electric power systems. However, the use of DC superconducting cable lines together with converters brings additional advantages as reduction of losses in cables and suitable lowering of refrigerating plant capacity, as well as the realization of the function of short-circuit currents limitation by means of the appropriate setting of converter equipment. Russian Federal Grid Company and its R&D Center started the construction of the DC HTS power transmission line which includes the cable itself, cryogenic equipment, AC/DC converters, terminals and cable coupling boxes. This line will connect two substations in Saint-Petersburg - 330 kV "Centralnaya" and 220 kV "RP-9". The length of this HTS transmission line will be about 2500 meters. Nowadays are developed all the elements of the line and technologies of the cable manufacturing. Two HTS cable samples, each 30 m length, have been made. This paper describes the results of cables tests.

  1. Molecular identification of SqKv1A. A candidate for the delayed rectifier K channel in squid giant axon

    PubMed Central

    1996-01-01

    We have cloned the cDNA for a squid Kvl potassium channel (SqKv1A). SqKv1A mRNA is selectively expressed in giant fiber lobe (GFL) neurons, the somata of the giant axons. Western blots detect two forms of SqKv1A in both GFL neuron and giant axon samples. Functional properties of SqKv1A currents expressed in Xenopus oocytes are very similar to macroscopic currents in GFL neurons and giant axons. Macroscopic K currents in GFL neuron cell bodies, giant axons, and in Xenopus oocytes expressing SqKv1A, activate rapidly and inactivate incompletely over a time course of several hundred ms. Oocytes injected with SqKv1A cRNA express channels of two conductance classes, estimated to be 13 and 20 pS in an internal solution containing 470 mM K. SqKv1A is thus a good candidate for the "20 pS" K channel that accounts for the majority of rapidly activating K conductance in both GFL neuron cell bodies and the giant axon. PMID:8882864

  2. Molecular identification of SqKv1A. A candidate for the delayed rectifier K channel in squid giant axon.

    PubMed

    Rosenthal, J J; Vickery, R G; Gilly, W F

    1996-09-01

    We have cloned the cDNA for a squid Kvl potassium channel (SqKv1A). SqKv1A mRNA is selectively expressed in giant fiber lobe (GFL) neurons, the somata of the giant axons. Western blots detect two forms of SqKv1A in both GFL neuron and giant axon samples. Functional properties of SqKv1A currents expressed in Xenopus oocytes are very similar to macroscopic currents in GFL neurons and giant axons. Macroscopic K currents in GFL neuron cell bodies, giant axons, and in Xenopus oocytes expressing SqKv1A, activate rapidly and inactivate incompletely over a time course of several hundred ms. Oocytes injected with SqKv1A cRNA express channels of two conductance classes, estimated to be 13 and 20 pS in an internal solution containing 470 mM K. SqKv1A is thus a good candidate for the "20 pS" K channel that accounts for the majority of rapidly activating K conductance in both GFL neuron cell bodies and the giant axon.

  3. Decrease of a Current Mediated by Kv1.3 Channels Causes Striatal Cholinergic Interneuron Hyperexcitability in Experimental Parkinsonism.

    PubMed

    Tubert, Cecilia; Taravini, Irene R E; Flores-Barrera, Eden; Sánchez, Gonzalo M; Prost, María Alejandra; Avale, María Elena; Tseng, Kuei Y; Rela, Lorena; Murer, Mario Gustavo

    2016-09-01

    The mechanism underlying a hypercholinergic state in Parkinson's disease (PD) remains uncertain. Here, we show that disruption of the Kv1 channel-mediated function causes hyperexcitability of striatal cholinergic interneurons in a mouse model of PD. Specifically, our data reveal that Kv1 channels containing Kv1.3 subunits contribute significantly to the orphan potassium current known as IsAHP in striatal cholinergic interneurons. Typically, this Kv1 current provides negative feedback to depolarization that limits burst firing and slows the tonic activity of cholinergic interneurons. However, such inhibitory control of cholinergic interneuron excitability by Kv1.3-mediated current is markedly diminished in the parkinsonian striatum, suggesting that targeting Kv1.3 subunits and their regulatory pathways may have therapeutic potential in PD therapy. These studies reveal unexpected roles of Kv1.3 subunit-containing channels in the regulation of firing patterns of striatal cholinergic interneurons, which were thought to be largely dependent on KCa channels. PMID:27568555

  4. Decrease of a Current Mediated by Kv1.3 Channels Causes Striatal Cholinergic Interneuron Hyperexcitability in Experimental Parkinsonism.

    PubMed

    Tubert, Cecilia; Taravini, Irene R E; Flores-Barrera, Eden; Sánchez, Gonzalo M; Prost, María Alejandra; Avale, María Elena; Tseng, Kuei Y; Rela, Lorena; Murer, Mario Gustavo

    2016-09-01

    The mechanism underlying a hypercholinergic state in Parkinson's disease (PD) remains uncertain. Here, we show that disruption of the Kv1 channel-mediated function causes hyperexcitability of striatal cholinergic interneurons in a mouse model of PD. Specifically, our data reveal that Kv1 channels containing Kv1.3 subunits contribute significantly to the orphan potassium current known as IsAHP in striatal cholinergic interneurons. Typically, this Kv1 current provides negative feedback to depolarization that limits burst firing and slows the tonic activity of cholinergic interneurons. However, such inhibitory control of cholinergic interneuron excitability by Kv1.3-mediated current is markedly diminished in the parkinsonian striatum, suggesting that targeting Kv1.3 subunits and their regulatory pathways may have therapeutic potential in PD therapy. These studies reveal unexpected roles of Kv1.3 subunit-containing channels in the regulation of firing patterns of striatal cholinergic interneurons, which were thought to be largely dependent on KCa channels.

  5. MicroRNA-Mediated Downregulation of the Potassium Channel Kv4.2 Contributes to Seizure Onset.

    PubMed

    Gross, Christina; Yao, Xiaodi; Engel, Tobias; Tiwari, Durgesh; Xing, Lei; Rowley, Shane; Danielson, Scott W; Thomas, Kristen T; Jimenez-Mateos, Eva M; Schroeder, Lindsay M; Pun, Raymund Y K; Danzer, Steve C; Henshall, David C; Bassell, Gary J

    2016-09-27

    Seizures are bursts of excessive synchronized neuronal activity, suggesting that mechanisms controlling brain excitability are compromised. The voltage-gated potassium channel Kv4.2, a major mediator of hyperpolarizing A-type currents in the brain, is a crucial regulator of neuronal excitability. Kv4.2 expression levels are reduced following seizures and in epilepsy, but the underlying mechanisms remain unclear. Here, we report that Kv4.2 mRNA is recruited to the RNA-induced silencing complex shortly after status epilepticus in mice and after kainic acid treatment of hippocampal neurons, coincident with reduction of Kv4.2 protein. We show that the microRNA miR-324-5p inhibits Kv4.2 protein expression and that antagonizing miR-324-5p is neuroprotective and seizure suppressive. MiR-324-5p inhibition also blocks kainic-acid-induced reduction of Kv4.2 protein in vitro and in vivo and delays kainic-acid-induced seizure onset in wild-type but not in Kcnd2 knockout mice. These results reveal an important role for miR-324-5p-mediated silencing of Kv4.2 in seizure onset. PMID:27681419

  6. Transmission grid access and pricing in Norway, Spain, and California: A comparative study

    SciTech Connect

    Gronli, H.; Gomez San Ramon, T.; Marnay, C.

    1999-09-01

    The openness of the transmission grid and the incentives given by transmission pricing form the foundation for retail and wholesale competition in the electricity market. The deregulated markets of Norway, Spain, and California all have introduced retail access and wholesale competition, although with different approaches to pricing of transmission grid services. This paper will briefly describe the three different solutions, and discuss some of their implications. Of the three electricity systems, Norway was the first to open the grid to competition in electricity trade. The Norwegian Energy Law of 1990 introduced open competition to wholesale and retail trade starting January 1991. In Spain, the Electricity Law of 1997 came into force early in 1998. Wholesale and retail markets in California were opened for competition on April 1, 1998, following the passage of Assembly Bill 1890, in August 1996. Introducing competition in electricity markets also implies introducing Third Party Access to the transmission grid. All potential competitors have to be given access to the grid in order to compete, no matter who owns the actual wires. This principle raises several challenges, notably, how to price transmission services. Who is to pay for which transmission services? The Norwegian grid is divided into three levels depending on its function. The transmission grid includes all parts of the national grid having a transmission function, meaning that some lower voltage levels also are included. In Spain, the definition of the transmission grid is similar, including the 400 kV and 220 kV national grid as well as lower voltage installations that could affect transmission operation or generation dispatch. For historic reasons, wholesale electricity transactions in the US are regulated by the federal government through the FERC. However, operations of utility systems within one state fall primarily under state jurisdiction. Because the utility systems in California generally are

  7. Supplement Analysis for the Transmission System Vegetation Management Program FEIS (DOE/EIS-0285/SA-62) - Rocky Reach - Maple Valley

    SciTech Connect

    Martin, Mark A.

    2002-04-16

    Vegetation Management along the Rocky Reach – Maple Valley No. 1 Transmission Line ROW from structure 98/2 to structure 110/1. The transmission line is a 500 kV line. BPA proposes to clear targeted vegetation along access roads and around tower structures that may impede the operation and maintenance of the subject transmission line. BPA plans to conduct vegetation management along existing access road and around structure landings for the purpose of maintaining access to structures site. All work will be in accordance with the National Electrical Safety Code and BPA standards.

  8. Inhibition of Kv channel expression by NSAIDs depolarizes membrane potential and inhibits cell migration by disrupting calpain signaling.

    PubMed

    Silver, Kristopher; Littlejohn, Alaina; Thomas, Laurel; Marsh, Elizabeth; Lillich, James D

    2015-12-15

    Clinical use of non-steroidal anti-inflammatory drugs (NSAIDs) is well known to cause gastrointestinal ulcer formation via several mechanisms that include inhibiting epithelial cell migration and mucosal restitution. The drug-affected signaling pathways that contribute to inhibition of migration by NSAIDs are poorly understood, though previous studies have shown that NSAIDs depolarize membrane potential and suppress expression of calpain proteases and voltage-gated potassium (Kv) channel subunits. Kv channels play significant roles in cell migration and are targets of NSAID activity in white blood cells, but the specific functional effects of NSAID-induced changes in Kv channel expression, particularly on cell migration, are unknown in intestinal epithelial cells. Accordingly, we investigated the effects of NSAIDs on expression of Kv1.3, 1.4, and 1.6 in vitro and/or in vivo and evaluated the functional significance of loss of Kv subunit expression. Indomethacin or NS-398 reduced total and plasma membrane protein expression of Kv1.3 in cultured intestinal epithelial cells (IEC-6). Additionally, depolarization of membrane potential with margatoxin (MgTx), 40mM K(+), or silencing of Kv channel expression with siRNA significantly reduced IEC-6 cell migration and disrupted calpain activity. Furthermore, in rat small intestinal epithelia, indomethacin and NS-398 had significant, yet distinct, effects on gene and protein expression of Kv1.3, 1.4, or 1.6, suggesting that these may be clinically relevant targets. Our results show that inhibition of epithelial cell migration by NSAIDs is associated with decreased expression of Kv channel subunits, and provide a mechanism through which NSAIDs inhibit cell migration and may contribute to NSAID-induced gastrointestinal (GI) toxicity.

  9. The Inhibitory Effects of Ca2+ Channel Blocker Nifedipine on Rat Kv2.1 Potassium Channels.

    PubMed

    Li, Xian-Tao; Li, Xiao-Qing; Hu, Xi-Mu; Qiu, Xiao-Yue

    2015-01-01

    It is well documented that nifedipine, a commonly used dihydropyridine Ca2+ channel blocker, has also significant interactions with voltage-gated K+ (Kv) channels. But to date, little is known whether nifedipine exerted an action on Kv2.1 channels, a member of the Shab subfamily with slow inactivation. In the present study, we explored the effects of nifedipine on rat Kv2.1 channels expressed in HEK293 cells. Data from whole-cell recording showed that nifedipine substantially reduced Kv2.1 currents with the IC50 value of 37.5 ± 5.7 μM and delayed the time course of activation without effects on the activation curve. Moreover, this drug also significantly shortened the duration of inactivation and deactivation of Kv2.1 currents in a voltage-dependent manner. Interestingly, the half-maximum inactivation potential (V1/2) of Kv2.1 currents was -11.4 ± 0.9 mV in control and became -38.5 ± 0.4 mV after application of 50 μM nifedipine. The large hyperpolarizing shift (27 mV) of the inactivation curve has not been reported previously and may result in more inactivation for outward delayed rectifier K+ currents mediated by Kv2.1 channels at repolarization phases. The Y380R mutant significantly increased the binding affinity of nifedipine to Kv2.1 channels, suggesting an interaction of nifedipine with the outer mouth region of this channel. The data present here will be helpful to understand the diverse effects exerted by nifedipine on various Kv channels.

  10. Functional interactions between residues in the S1, S4, and S5 domains of Kv2.1.

    PubMed

    Bocksteins, E; Ottschytsch, N; Timmermans, J-P; Labro, A J; Snyders, D J

    2011-06-01

    The voltage-gated potassium channel subunit Kv2.1 forms heterotetrameric channels with the silent subunit Kv6.4. Chimeric Kv2.1 channels containing a single transmembrane segment from Kv6.4 have been shown to be functional. However, a Kv2.1 chimera containing both S1 and S5 from Kv6.4 was not functional. Back mutation of individual residues in this chimera (to the Kv2.1 counterpart) identified four positions that were critical for functionality: A200V and A203T in S1, and T343M and P347S in S5. To test for possible interactions in Kv2.1, we used substitutions with charged residues and tryptophan for the outermost pair 203/347. Combinations of substitutions with opposite charges at both T203 and S347 were tolerated but resulted in channels with altered gating kinetics, as did the combination of negatively charged aspartate substitutions. Double mutant cycle analysis with these mutants indicated that both residues are energetically coupled. In contrast, replacing both residues with a positively charged lysine together (T203K + S347K) was not tolerated and resulted in a folding or trafficking deficiency. The nonfunctionality of the T203K + S347K mutation could be restored by introducing the R300E mutation in the S4 segment of the voltage sensor. These results indicate that these specific S1, S4, and S5 residues are in close proximity and interact with each other in the functional channel, but are also important determinants for Kv2.1 channel maturation. These data support the view of an anchoring interaction between S1 and S5, but indicate that this interaction surface is more extensive than previously proposed.

  11. Prospects of long-distance HTS DC power transmission systems

    NASA Astrophysics Data System (ADS)

    Romashov, M. A.; Sytnikov, V. E.; Shakarian, Y. G.; Ivanov, Y. V.

    2014-05-01

    Continual improvement of technologies for the safe use of power resources is a key to sustainable development of a human society. In particular, high-temperature superconductivity (HTS) should be used to meet the growing needs of the electric-power industry. It is known that HTS power cables allow us to increase the level of transmitted energy to several GW at voltage of 66-110 kV. HTS power cables of a coaxial design are almost ideal non-polluting system shielding electromagnetic field. In the present work we have tried to analyze various configurations of HTS power transmission systems, estimate the cable transmission capacitance depending on distance, and characterize reliability and efficiency of the systems.

  12. Supplement Analysis for the Transmission System Vegetation Management Program FEIS (DOE/EIS-0285/SA-124 (Echo Lake-Maple Valley #1 [Mile 9-16], Adno 8258)

    SciTech Connect

    Shurtliff, Aaron

    2003-02-18

    Vegetation Management for portion of the Echo Lake – Maple Valley #1 500 kV transmission line located from tower structure 9/2 to 16/5. BPA proposes to clear targeted vegetation within the Right-of-Ways along access roads and around towers that may impede the operation and maintenance of the subject transmission lines. See Section 1.4 of the attached checklists for a complete description of the proposed action.

  13. Supplement Analysis for the Transmission System Vegetation Management Program FEIS (DOE/EIS-0285/SA-125 (Echo Lake-Maple Valley #1 [Mile 1-9], Adno 8258)

    SciTech Connect

    Shurtliff, Aaron

    2003-02-18

    Vegetation Management for portion of the Echo Lake – Maple Valley #1 500 kV transmission line located from tower structure 1/1 to 9/2. BPA proposes to clear targeted vegetation within the Right-of-Ways along access roads and around towers that may impede the operation and maintenance of the subject transmission lines. See Section 1.4 of the attached checklists for a complete description of the proposed action.

  14. Canby Area Service Project : Substation and Associated Transmission Line : Environmental Assessment.

    SciTech Connect

    United States. Bonneville Power Administration.

    1992-02-01

    Bonneville Power Administration (BPA) provides power to Surprise Valley Electrification Corporation (SVEC) in Modoc County, California. BPA uses PacificCorp's substation and transmission facilities between Alturas and Canby, California to transfer power to SVEC's Canby Substation. In the next year, SVEC expects increased industrial, agricultural, and residential electric loads on their 69-kV transmission system south of Canby. SVEC's substation can accommodate only about 10 percent of the expected additional electric load. BPA's proposed action is intended to meet SVEC's increasing electric load. BPA proposes to meet SVEC's increasing energy load by tapping into BPA's existing BPA Malin-Warner 230-kV transmission line, and building an 7.9-mile transmission line to a new BPA substation. BPA proposes to build the new substation next to the west side of SVEC's Canby Substation (Figure 1). This new substation will allow SVEC to move the additional power over their existing transmission or distribution lines. This report is the environmental assessment of the potential impact of the proposed project. The assessment determined that no environmental impact statement'' is not required.

  15. Canby Area Service Project substation and associated transmission line. Environmental Assessment

    SciTech Connect

    Not Available

    1992-02-01

    Bonneville Power Administration (BPA) provides power to Surprise Valley Electrification Corporation (SVEC) in Modoc County, California. BPA uses PacificCorp`s substation and transmission facilities between Alturas and Canby, California to transfer power to SVEC`s Canby Substation. In the next year, SVEC expects increased industrial, agricultural, and residential electric loads on their 69-kV transmission system south of Canby. SVEC`s substation can accommodate only about 10 percent of the expected additional electric load. BPA`s proposed action is intended to meet SVEC`s increasing electric load. BPA proposes to meet SVEC`s increasing energy load by tapping into BPA`s existing BPA Malin-Warner 230-kV transmission line, and building an 7.9-mile transmission line to a new BPA substation. BPA proposes to build the new substation next to the west side of SVEC`s Canby Substation (Figure 1). This new substation will allow SVEC to move the additional power over their existing transmission or distribution lines. This report is the environmental assessment of the potential impact of the proposed project. The assessment determined that no ``environmental impact statement`` is not required.

  16. High-voltage testing of a 500-kV dc photocathode electron gun.

    PubMed

    Nagai, Ryoji; Hajima, Ryoichi; Nishimori, Nobuyuki; Muto, Toshiya; Yamamoto, Masahiro; Honda, Yosuke; Miyajima, Tsukasa; Iijima, Hokuto; Kuriki, Masao; Kuwahara, Makoto; Okumi, Shoji; Nakanishi, Tsutomu

    2010-03-01

    A high-voltage dc photocathode electron gun was successfully conditioned up to a voltage of 550 kV and a long-time holding test for 8 h was demonstrated at an acceleration voltage of 500 kV. The dc photocathode electron gun is designed for future light sources based on energy-recovery linac and consists of a Cockcroft-Walton generator, a segmented cylindrical ceramic insulator, guard-ring electrodes, a support-rod electrode, a vacuum chamber, and a pressurized insulating gas tank. The segmented cylindrical ceramic insulator and the guard-ring electrodes were utilized to prevent any damage to the insulator from electrons emitted by the support-rod electrode.

  17. Development of 500 kV DC PPLP-insulated oil-filled submarine cable

    SciTech Connect

    Fujimori, A.; Tanaka, T.; Takashima, H.; Imajo, T.; Hata, R.; Tanabe, T.; Yoshida, S.; Kakihana, T.

    1996-01-01

    This paper outlines the development of a 500 kV DC oil-filled submarine cable capable of transmitting 2,800 MW with {+-} 500 kV 2800A bipole system. Polypropylene Laminated Paper (PPL) was employed as the insulation material, which is the worlds first application to DC cables. The conductor size is 3,000 mm{sup 2}, which is the largest size for submarine cables ever put into practical use. Through various fundamental and prototype tests, the cable proved to have excellent electrical characteristics for DC voltage as well as transient overvoltage. The cable and accessories are currently undergoing a long-term accelerated aging test as the final confirmation of their reliability and stability.

  18. Transmission of Mumps

    MedlinePlus

    ... Articles Related Links World Health Organization Medline Plus Transmission of Mumps Language: English Español (Spanish) Recommend on ... Answers for Patients . Top of Page Related Pages Transmission for Healthcare Providers Cover Your Cough Clean Hands ...

  19. Chickenpox (Varicella): Transmission

    MedlinePlus

    ... Multimedia Related Links Medline Plus Healthfinder.gov Shingles Transmission Language: English Español (Spanish) Recommend on Facebook Tweet ... not shingles. For more information about shingles, see Transmission . When Is a Person Contagious? A person with ...

  20. Development of battery powered 100 kV dc power supply

    NASA Astrophysics Data System (ADS)

    Verma, Rishi; Shyam, A.; Nair, Lakshmi

    2006-10-01

    The increased interest in pulsed power field applications has generated the need for development of compact and remotely operated chargers driven by rechargeable batteries. With this objective, a compact and portable dc to dc Converter has been developed which has an output rating of 100kV, 0.4mA. The high voltage generation scheme uses a hybrid approach. The overall idea behind implementation of hybrid concept is to optimize voltage upliftment with suitable techniques for maximizing power delivered per unit volume. The proposed converter provides this feature and uses flyback converter in association with Cockcroft-Walton Multiplier [M. Jullian, Cockcroft-Walton Multiplier Optimum Design Guide V2.0, August 2005 (http//www.blazelabes.com)] for the generation of 100kV dc from 12V dc source, i.e., normal battery. In the first stage 12V dc is modulated/chopped into series of high frequency pulses by pulse width modulator and then increased in level up to 16kVpp by step up flyback transformer. Further by using n stage half wave series Cockcroft-Walton multiplier the voltage is stepped up to the level of 100kV. As switching device, state of the art metal-oxide-semiconductor field-effect transistor has been used. The obtained voltage multiplier cascade efficiency is 82.64%, whereas overall power conversion efficiency of the charging power supply is 85.47%. The control unit has been fiber optically isolated from high voltage unit due to safety consideration. The presented article explores complete design and development approach of compact and portable 100kV dc power supply which can be used for a variety of applications such as x-ray generation, ion implantation, charge particle acceleration, radio isotope production, etc.

  1. 7. VIEW OF 100 kV SWITCHYARD WITH MISSOURI RIVER IN ...

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

    7. VIEW OF 100 kV SWITCHYARD WITH MISSOURI RIVER IN THE BACKGROUND. ALONG THE LEFT SIDE FROM THE FOREGROUND ARE THE U.S. GOVERNMENT STORAGE SHED, TOOL HOUSE, THREE-STALL GARAGE, AND PARTIAL VIEW OF POWERHOUSE ADDITION. VIEW TO NORTHEAST. - Rainbow Hydroelectric Facility, On north bank of Missouri River 2 miles Northeast of Great Falls, & end of Rainbow Dam Road, Great Falls, Cascade County, MT

  2. Molecular mechanism for depolarization-induced modulation of Kv channel closure.

    PubMed

    Labro, Alain J; Lacroix, Jerome J; Villalba-Galea, Carlos A; Snyders, Dirk J; Bezanilla, Francisco

    2012-11-01

    Voltage-dependent potassium (Kv) channels provide the repolarizing power that shapes the action potential duration and helps control the firing frequency of neurons. The K(+) permeation through the channel pore is controlled by an intracellularly located bundle-crossing (BC) gate that communicates with the voltage-sensing domains (VSDs). During prolonged membrane depolarizations, most Kv channels display C-type inactivation that halts K(+) conduction through constriction of the K(+) selectivity filter. Besides triggering C-type inactivation, we show that in Shaker and Kv1.2 channels (expressed in Xenopus laevis oocytes), prolonged membrane depolarizations also slow down the kinetics of VSD deactivation and BC gate closure during the subsequent membrane repolarization. Measurements of deactivating gating currents (reporting VSD movement) and ionic currents (BC gate status) showed that the kinetics of both slowed down in two distinct phases with increasing duration of the depolarizing prepulse. The biphasic slowing in VSD deactivation and BC gate closure was strongly correlated in time and magnitude. Simultaneous recordings of ionic currents and fluorescence from a probe tracking VSD movement in Shaker directly demonstrated that both processes were synchronized. Whereas the first slowing originates from a stabilization imposed by BC gate opening, the subsequent slowing reflects the rearrangement of the VSD toward its relaxed state (relaxation). The VSD relaxation was observed in the Ciona intestinalis voltage-sensitive phosphatase and in its isolated VSD. Collectively, our results show that the VSD relaxation is not kinetically related to C-type inactivation and is an intrinsic property of the VSD. We propose VSD relaxation as a general mechanism for depolarization-induced slowing of BC gate closure that may enable Kv1.2 channels to modulate the firing frequency of neurons based on the depolarization history. PMID:23071266

  3. Pseudosaccharin amines as potent and selective KV1.5 blockers.

    PubMed

    Lloyd, John; Finlay, Heather J; Kover, Alexander; Johnson, James; Pi, Zulan; Jiang, Ji; Neels, James; Cavallaro, Cullen; Wexler, Ruth; Conder, Mary Lee; Shi, Hong; Li, Danshi; Sun, Huabin; Chimalakonda, Anjaneya; Huang, Christine; Salvati, Mark; Levesque, Paul

    2015-11-01

    Phenethyl aminoheterocycles like compound 1 were known to be potent I(Kur) blockers although they lacked potency in vivo. Modification of the heterocycle led to the design and synthesis of pseudosaccharin amines. Compounds such as 14, 17d and 21c were found to be potent K(V)1.5 blockers and selective over other cardiac ion channels. These compounds had potent pharmacodynamic activity, however, they also showed off-target activities such as hemodynamic effects.

  4. Optimizing Monoscopic kV Fluoro Acquisition for Prostate Intrafraction Motion Evaluation

    PubMed Central

    Adamson, Justus; Wu, Qiuwen

    2008-01-01

    Monoscopic kV imaging during radiotherapy has been recently implemented for prostate intrafraction motion evaluation. However, the accuracy of 3D localization techniques from monoscopic imaging of prostate and the effect of acquisition parameters on the 3D accuracy have not been studied in detail, with imaging dose remaining a concern. In this paper we investigate methods to optimize the kV acquisition parameters and imaging protocol to achieve improved 3D localization and 2D image registration accuracy for minimal imaging dose. Prostate motion during radiotherapy was simulated using existing cine-MRI measurements, and was used to investigate the accuracy of various 3D localization techniques and the effect of kV acquisition protocol. We also investigated the relationship between mAs and the accuracy of the 2D image registration for localization of fiducial markers, and we measured imaging dose for a 30-cm diameter phantom to evaluate the necessary dose to achieve acceptable image registration accuracy. Simulations showed that the error in assuming the shortest path to localize the prostate in 3D using monoscopic imaging during a typical IMRT fraction will be less than ~1.5 mm for 95% of localizations, but will also depend on prostate motion distribution, treatment duration, and image acquisition and treatment protocol. Most uncertainty cannot be reduced from higher imaging frequency or acquiring during gantry rotation between beams. Measured maximum surface dose to the cylindrical phantom from monoscopic kV intrafraction acquisitions varied between 0.4–5.5 mGy, depending on acquisition protocol, and was lower than the required dose for CBCT (21.1 mGy). Imaging dose can be lowered by ~15–40% when mAs is optimized with acquisition angle. Images acquired during MV beam delivery require increased mAs to obtain the same level of registration accuracy, with mAs/registration increasing roughly linearly with field size and dose rate. PMID:19075358

  5. The T1 domain of Kv1.3 mediates intracellular targeting to axons.

    PubMed

    Rivera, Jacqueline F; Chu, Po-Ju; Arnold, Don B

    2005-10-01

    Shaker K+ channels play an important role in modulating electrical excitability of axons. Recent work has demonstrated that the T1 tetramerization domain of Kv1.2 is both necessary and sufficient for targeting of the channel to the axonal surface [Gu, C., Jan, Y.N. & Jan, L.Y. (2003) Science,301, 646-649]. Here we use a related channel, Kv1.3, as a model to investigate cellular mechanisms that mediate axonal targeting. We show that the T1 domain of Kv1.3 is necessary and sufficient to mediate targeting of the channel to the axonal surface in pyramidal neurons in slices of cortex from neonatal rat. The T1 domain is also sufficient to cause preferential axonal localization of intracellular protein, which indicates that the domain probably does not work through compartment-specific endocytosis or compartment-specific vesicle docking. To determine whether the T1 domain mediates axonal trafficking of transport vesicles, we compared the trafficking of vesicles containing green fluorescent protein-labelled transferrin receptor with those containing the same protein fused with the T1 domain in living cortical neurons. Vesicles containing the wild-type transferrin receptor did not traffic to the axon, in accord with previously published results; however, those containing the transferrin receptor fused to T1 did traffic to the axon. These results are consistent with the T1 domain of Kv1.3 mediating axonal targeting by causing transport vesicles to traffic to axons and they represent the first evidence that such a mechanism might underlie axonal targeting. PMID:16262625

  6. Supplement Analysis for the Transmission System Vegetation Management Program FEIS (DOE/EIS-0285/SA-15)

    SciTech Connect

    N /A

    2001-06-19

    . The subject transmission lines range from 115kV to 230kV and are made up of accompanying access roads, steel and wooden transmission line structures and associated switching platforms. The minimum clearance ranges from 21 feet for 115kV lines to 23 feet for 230kV lines. ROW easement widths vary along the length of the project. Vegetation control for this project is designed to provide a 3 year maintenance free interval. In summary, the overall vegetation management scheme will be to selectively remove tall growing vegetation then apply selective herbicide treatment using cut stump applications.

  7. Poster — Thur Eve — 10: Partial kV CBCT, complete kV CBCT and EPID in breast treatment: a dose comparison study for skin, breasts, heart and lungs

    SciTech Connect

    Roussin, E; Archambault, L K; Wierzbicki, W

    2014-08-15

    The advantages of kilovoltage cone beam CT (kV CBCT) imaging over electronic portal imaging device (EPID) such as accurate 3D anatomy, soft tissue visualization, fast rigid registration and enhanced precision on patient positioning has lead to its increasing use in clinics. The benefits of this imaging technique are at the cost of increasing the dose to healthy surrounding organs. Our center has moved toward the use of daily partial rotation kV CBCT to restrict the dose to healthy tissues. This study aims to better quantify radiation doses from different image-guidance techniques such as tangential EPID, complete and partial kV CBCT for breast treatments. Cross-calibrated ionization chambers and kV calibrated Gafchromic films were used to measure the dose to the heart, lungs, breasts and skin. It was found that performing partial kV CBCT decreases the heart dose by about 36%, the lungs dose by 31%, the contralateral breast dose by 41% and the ipsilateral breast dose by 43% when compared to a full rotation CBCT. The skin dose measured for a full rotation CBCT was about 0.8 cGy for the contralateral breast and about 0.3 cGy for the ipsilateral breast. The study is still ongoing and results on skin doses for partial rotation kV CBCT as well as for tangential EPID images are upcoming.

  8. SU-E-I-29: Care KV: Dose It Influence Radiation Dose in Non-Contrast Examination of CT Abdomen/pelvis?

    SciTech Connect

    Zhang, J; Ganesh, H; Weir, V

    2015-06-15

    Purpose: CARE kV is a tool that automatically recommends optimal kV setting for individual patient for specific CT examination. The use of CARE kV depends on topogram and the user-selected contrast behavior. CARE kV is expected to reduce radiation dose while improving image quality. However, this may work only for certain groups of patients and/or certain CT examinations. This study is to investigate the effects of CARE kV on radiation dose of non-contrast examination of CT abdomen/pelvis. Methods: Radiation dose (CTDIvol and DLP) from patients who underwent abdomen/pelvis non-contrast examination with and without CARE kV were retrospectively reviewed. All patients were scanned in the same scanner (Siemens Somatom AS64). To mitigate any possible influences due to technologists’ unfamiliarity with the CARE kV, the data with CARE kV were retrieved 1.5 years after the start of CARE kV usage. T-test was used for significant difference in radiation dose. Results: Volume CTDIs and DLPs from 18 patients before and 24 patients after the use of CARE kV were obtained in a duration of one month. There is a slight increase in both average CTDIvol and average DLP with CARE kV compared to those without CARE kV (25.52 mGy vs. 22.65 mGy for CTDIvol; 1265.81 mGy-cm vs. 1199.19 mGy-cm). Statistically there was no significant difference. Without CARE kV, 140 kV was used in 9 of 18 patients, while with CARE KV, 140 kV was used in 15 of 24 patients. 80kV was not used in either group. Conclusion: The use of CARE kV may save time for protocol optimization and minimize variability among technologists. Radiation dose reduction was not observed in non-contrast examinations of CT abdomen/pelvis. This was partially because our CT protocols were tailored according to patient size before CARE kV and partially because of large size patients.

  9. 250 kV 6 mA compact Cockcroft-Walton high-voltage power supply.

    PubMed

    Ma, Zhan-Wen; Su, Xiao-Dong; Lu, Xiao-Long; Wei, Zhen; Wang, Jun-Run; Huang, Zhi-Wu; Miao, Tian-You; Su, Tong-Ling; Yao, Ze-En

    2016-08-01

    A compact power supply system for a compact neutron generator has been developed. A 4-stage symmetrical Cockcroft-Walton circuit is adopted to produce 250 kV direct current high-voltage. A 2-stage 280 kV isolation transformer system is used to drive the ion source power supply. For a compact structure, safety, and reliability during the operation, the Cockcroft-Walton circuit and the isolation transformer system are enclosed in an epoxy vessel containing the transformer oil whose size is about ∅350 mm × 766 mm. Test results indicate that the maximum output voltage of the power supply is 282 kV, and the stability of the output voltage is better than 0.63% when the high voltage power supply is operated at 250 kV, 6.9 mA with the input voltage varying ±10%. PMID:27587170

  10. Structure-function study of a chlorotoxin-chimer and its activity on Kv1.3 channels.

    PubMed

    Huys, Isabelle; Waelkens, Etienne; Tytgat, Jan

    2004-04-15

    Chlorotoxin has been isolated from the venom of the scorpion Leiurus quinquestriatus and characterized as a 4.1kDa peptide, containing a lysine at position 27 that is also present in many Kv-blocking toxins. Because chlorotoxin shows no affinity for Kv-channels, we intended to design, express and purify a chlorotoxin-chimer, containing the active binding site (beta-sheet) of a very potent Kv1-channel blocking peptide, agitoxin 2, by mutating three original residues in the chlorotoxin molecule. Several derivatives of the chimer, gradually missing one additional amino acid residue at the N-terminal side of the peptide, were produced and identified chromatographically. In contrast to chlorotoxin, these chimer derivatives are capable of blocking cloned Kv1-channels.

  11. 250 kV 6 mA compact Cockcroft-Walton high-voltage power supply

    NASA Astrophysics Data System (ADS)

    Ma, Zhan-Wen; Su, Xiao-Dong; Lu, Xiao-Long; Wei, Zhen; Wang, Jun-Run; Huang, Zhi-Wu; Miao, Tian-You; Su, Tong-Ling; Yao, Ze-En

    2016-08-01

    A compact power supply system for a compact neutron generator has been developed. A 4-stage symmetrical Cockcroft-Walton circuit is adopted to produce 250 kV direct current high-voltage. A 2-stage 280 kV isolation transformer system is used to drive the ion source power supply. For a compact structure, safety, and reliability during the operation, the Cockcroft-Walton circuit and the isolation transformer system are enclosed in an epoxy vessel containing the transformer oil whose size is about ∅350 mm × 766 mm. Test results indicate that the maximum output voltage of the power supply is 282 kV, and the stability of the output voltage is better than 0.63% when the high voltage power supply is operated at 250 kV, 6.9 mA with the input voltage varying ±10%.

  12. 250 kV 6 mA compact Cockcroft-Walton high-voltage power supply.

    PubMed

    Ma, Zhan-Wen; Su, Xiao-Dong; Lu, Xiao-Long; Wei, Zhen; Wang, Jun-Run; Huang, Zhi-Wu; Miao, Tian-You; Su, Tong-Ling; Yao, Ze-En

    2016-08-01

    A compact power supply system for a compact neutron generator has been developed. A 4-stage symmetrical Cockcroft-Walton circuit is adopted to produce 250 kV direct current high-voltage. A 2-stage 280 kV isolation transformer system is used to drive the ion source power supply. For a compact structure, safety, and reliability during the operation, the Cockcroft-Walton circuit and the isolation transformer system are enclosed in an epoxy vessel containing the transformer oil whose size is about ∅350 mm × 766 mm. Test results indicate that the maximum output voltage of the power supply is 282 kV, and the stability of the output voltage is better than 0.63% when the high voltage power supply is operated at 250 kV, 6.9 mA with the input voltage varying ±10%.

  13. Kv1.3 potassium channels are localized in the immunological synapse formed between cytotoxic and target cells

    PubMed Central

    Panyi, G.; Vámosi, G.; Bacsó, Z.; Bagdány, M.; Bodnár, A.; Varga, Z.; Gáspár, R.; Mátyus, L.; Damjanovich, S.

    2004-01-01

    Membrane proteins of cytotoxic T cells specifically reorganize to form an immunological synapse (IS) on interaction with their specific target. In this paper, we investigated the redistribution of Kv1.3 channels, which are the dominant voltage-gated potassium channels, in the plasma membrane of allogen-activated human cytotoxic T lymphocytes (CTLs) on interacting with their specific target cells. Kv1.3 channels bearing a FLAG epitope were expressed in the CTLs and the cell-surface distribution of fluorescently labeled ion channels was determined from confocal laser-scanning microscopy images. FLAG epitope-tagged Kv1.3 channels showed a patchy distribution in CTLs not engaged with target cells, whereas the channels were accumulated in the IS formed between CTLs and specific target lymphocytes. Localization of Kv1.3 channels in the IS might open an unrevealed possibility in the regulation of ion channel activity by signaling molecules accumulated in the IS. PMID:14745040

  14. A functional Kv1.2-hERG chimaeric channel expressed in Pichia pastoris

    NASA Astrophysics Data System (ADS)

    Dhillon, Mandeep S.; Cockcroft, Christopher J.; Munsey, Tim; Smith, Kathrine J.; Powell, Andrew J.; Carter, Paul; Wrighton, David C.; Rong, Hong-Lin; Yusaf, Shahnaz P.; Sivaprasadarao, Asipu

    2014-02-01

    Members of the six-transmembrane segment family of ion channels share a common structural design. However, there are sequence differences between the members that confer distinct biophysical properties on individual channels. Currently, we do not have 3D structures for all members of the family to help explain the molecular basis for the differences in their biophysical properties and pharmacology. This is due to low-level expression of many members in native or heterologous systems. One exception is rat Kv1.2 which has been overexpressed in Pichia pastoris and crystallised. Here, we tested chimaeras of rat Kv1.2 with the hERG channel for function in Xenopus oocytes and for overexpression in Pichia. Chimaera containing the S1-S6 transmembrane region of HERG showed functional and pharmacological properties similar to hERG and could be overexpressed and purified from Pichia. Our results demonstrate that rat Kv1.2 could serve as a surrogate to express difficult-to-overexpress members of the six-transmembrane segment channel family.

  15. Side pockets provide the basis for a new mechanism of Kv channel–specific inhibition

    PubMed Central

    Marzian, Stefanie; Stansfeld, Phillip J; Rapedius, Markus; Rinné, Susanne; Nematian-Ardestani, Ehsan; Abbruzzese, Jennifer L; Steinmeyer, Klaus; Sansom, Mark S P; Sanguinetti, Michael C; Baukrowitz, Thomas; Decher, Niels

    2015-01-01

    Most known small-molecule inhibitors of voltage-gated ion channels have poor subtype specificity because they interact with a highly conserved binding site in the central cavity. Using alanine-scanning mutagenesis, electrophysiological recordings and molecular modeling, we have identified a new drug-binding site in Kv1.x channels. We report that Psora-4 can discriminate between related Kv channel subtypes because, in addition to binding the central pore cavity, it binds a second, less conserved site located in side pockets formed by the backsides of S5 and S6, the S4–S5 linker, part of the voltage sensor and the pore helix. Simultaneous drug occupation of both binding sites results in an extremely stable nonconducting state that confers high affinity, cooperativity, use-dependence and selectivity to Psora-4 inhibition of Kv1.x channels. This new mechanism of inhibition represents a molecular basis for the development of a new class of allosteric and selective voltage-gated channel inhibitors. PMID:23728494

  16. Usefulness of targeting lymphocyte Kv1.3-channels in the treatment of respiratory diseases.

    PubMed

    Kazama, Itsuro; Tamada, Tsutomu; Tachi, Masahiro

    2015-10-01

    T lymphocytes predominantly express delayed rectifier K(+)-channels (Kv1.3) in their plasma membranes. Patch-clamp studies revealed that the channels play crucial roles in facilitating the calcium influx necessary to trigger lymphocyte activation and proliferation. Using selective channel inhibitors in experimental animal models, in vivo studies further revealed the clinically relevant relationship between the channel expression and the development of chronic respiratory diseases, in which chronic inflammation or the overstimulation of cellular immunity in the airways is responsible for the pathogenesis. In chronic respiratory diseases, such as chronic obstructive pulmonary disease, asthma, diffuse panbronchiolitis and cystic fibrosis, in addition to the supportive management for the symptoms, the anti-inflammatory effects of macrolide antibiotics were shown to be effective against the over-activation or proliferation of T lymphocytes. Recently, we provided physiological and pharmacological evidence that macrolide antibiotics, together with calcium channel blockers, HMG-CoA reductase inhibitors, and nonsteroidal anti-inflammatory drugs, effectively suppress the Kv1.3-channel currents in lymphocytes, and thus exert anti-inflammatory or immunomodulatory effects. In this review article, based on the findings obtained from recent in vivo and in vitro studies, we address the novel therapeutic implications of targeting the lymphocyte Kv1.3-channels for the treatment of chronic or acute respiratory diseases.

  17. A 6 kV arbitrary waveform generator for the Tevatron Electron Lens

    SciTech Connect

    Pfeffer, H.; Saewert, G.

    2011-11-09

    This paper reports on a 6 kV modulator built and installed at Fermilab to drive the electron gun anode for the Tevatron Electron Lens (TEL). The TEL was built with the intention of shifting the individual (anti)proton bunch tunes to even out the tune spread among all 36 bunches with the desire of improving Tevatron integrated luminosity. This modulator is essentially a 6 kV arbitrary waveform generator that enables the TEL to define the electron beam intensity on a bunch-by-bunch basis. A voltage waveform is constructed having a 7 μs duration that corresponds to the tune shift requirements of a 12-bunch (anti)proton beam pulse train. This waveform is played out for any one or all three bunch trains in the Tevatron. The programmed waveform voltages transition to different levels at time intervals corresponding to the 395 ns bunch spacing. In addition, complex voltage waveforms can be played out at a sustained rate of 143 kHz over the full 6 kV output range. This paper describes the novel design of the inductive adder topology employing five transformers. It describes the design aspects that minimize switching losses for this multi-kilovolt, high repetition rate and high duty factor application.

  18. A 200 kV fast rise time, low jitter, trigger system with magnetic pulse sharpener

    SciTech Connect

    Jaitly, N.C.; Coleman, M.D.; Ramrus, A.; Earley, L.M.; Downing, J.N.; Reisch, H.H.; Caudill, L.D.; Eversol, S.A.

    1992-09-01

    The DARHT Facility is being designed at Los Alamos national Laboratory to produce high resolution flash radiographs of hydrodynamic experiments. Two linear induction accelerators (LIA), each in the range of 16 to 20 MeV, will be used to produce intense bremsstrahlung X-ray pulses of short duration (60 ns flat top). Each LIA will produce a 3 kA, high brightness, electron beam using a 4 MeV injector and a series of 250 kV induction cells. Technology demonstration of key accelerator subsystems is under progress at the DARHT Integrated Test Stand (ITS). The eight inductions cells present in the ITS are driven by a Maxwell prototype Induction Cell Pulsed Power supply (ICPPS) which provides 250 kV, 70 ns pulses via four Blumieins. Each Blumiein drives two cells and is triggered using independently controlled trigger units. This turnkey DARHT Trigger System, consisting of four separate trigger units, provides 200 kV trigger pulses with low jitter and fast rise time to each of the four Blumiein coaxial spark gaps. Details of the trigger system design and results obtained during extensive testing at Maxwell are described.

  19. A 6 kV arbitrary waveform generator for the Tevatron Electron Lens

    DOE PAGES

    Pfeffer, H.; Saewert, G.

    2011-11-09

    This paper reports on a 6 kV modulator built and installed at Fermilab to drive the electron gun anode for the Tevatron Electron Lens (TEL). The TEL was built with the intention of shifting the individual (anti)proton bunch tunes to even out the tune spread among all 36 bunches with the desire of improving Tevatron integrated luminosity. This modulator is essentially a 6 kV arbitrary waveform generator that enables the TEL to define the electron beam intensity on a bunch-by-bunch basis. A voltage waveform is constructed having a 7 μs duration that corresponds to the tune shift requirements of amore » 12-bunch (anti)proton beam pulse train. This waveform is played out for any one or all three bunch trains in the Tevatron. The programmed waveform voltages transition to different levels at time intervals corresponding to the 395 ns bunch spacing. In addition, complex voltage waveforms can be played out at a sustained rate of 143 kHz over the full 6 kV output range. This paper describes the novel design of the inductive adder topology employing five transformers. It describes the design aspects that minimize switching losses for this multi-kilovolt, high repetition rate and high duty factor application.« less

  20. DEVELOPMENT TESTING OF THE U.S. COMMON LONG PULSE SOURCE AT 120KV

    SciTech Connect

    Vella, M.C.; Cooper, W.S.; Pincosy, P.A.

    1987-12-01

    The U.S. magnetic fusion energy program has developed a single design long pulse neutral beam source for TFTR, MFTF-B, and DIII-D. The arc is a very compact axial magnetic line cusp. The accelerator is an actively cooled tetrode with water cooled grid tubes of shaped molybdenum forming 'slot' beamlets. DIII-D and MFTF-B configurations have an 80 kV accelerator gap, with 12 x 48 cm aperture, and a 10 meter 'module' focus. TFTR modules are unfocused, with a 120 kV gap and 12 x 43 cm mask. The first CLPS was tested in the TFTR configuration, at 120 kV, 2 seconds. Optimum current was 73 Amperes, or 1.76 ppervs (deuterium), with 80% - 85% atomic fraction. Optimum divergence of ions plus neutrals was 0.4' parallel to the slots, and 0.7' perpendicular to the slots ( l / e half angle). The combination of an axial cusp magnetic bucket and slot accelerator apertures gives the CLPS about twice the beam power per unit cross section of other long pulse sources, plus lower divergence in the direction parallel to the slots.

  1. Development testing of the U. S. common long pulse source at 120 kV

    SciTech Connect

    Vella, M.C.; Cooper, W.S.; Pincosy, P.A.; Pyle, R.V.; Weber, P.D.; Wells, R.P.

    1988-11-01

    The U. S. magnetic fusion energy program has developed a single design, long-pulse neutral beam source for TFTR, MFTF-B, and DIII-D. The arc is a very compact axial magnetic line cusp. The accelerator is an actively cooled tetrode with water-cooled grid tubes of shaped molybdenum forming ''slot'' beamlets. DIII-D and MFTF-B configurations have an 80-kV accelerator gap, with a 12 x 18 cm aperture, and a 10-m ''module'' focus. TFTR modules are unfocused, with a 120-kV gap and 12 x 43-cm mask. The first CLPS was tested in the TFTR configuration, at 120 kV, 2s. Optimum current was 73 A, or 1.76 ..mu..pervs (deuterium), with 80%--85% atomic fraction. Optimum divergence of ions plus neutrals was 0.4/sup 0/ parallel to the slots, and 0.7/sup 0/ perpendicular to the slots (1/e half-angle). The combination of an axial cusp magnetic bucket and slot accelerator apertures gives the common long pulse source about twice the beam power per unit cross section of other long pulse sources, plus lower divergence in the direction parallel to the slots.

  2. SU-E-J-22: A Feasibility Study On KV-Based Whole Breast Radiation Patient Setup

    SciTech Connect

    Huang, Q; Zhang, M; Yue, N; Chen, T

    2015-06-15

    Purpose: In room kilovoltage x-ray (kV) imaging provides higher contrast than Megavoltage (MV) imaging with faster acquisition time compared with on-board cone-beam computed tomography (CBCT), thus improving patient setup accuracy and efficiency. In this study we evaluated the clinical feasibility of utilizing kV imaging for whole breast radiation patient setup. Methods: For six breast cancer patients with whole breast treatment plans using two opposed tangential fields, MV-based patient setup was conducted by aligning patient markers with in room lasers and MV portal images. Beam-eye viewed kV images were acquired using Varian OBI system after the set up process. In house software was developed to transfer MLC blocks information overlaying onto kV images to demonstrate the field shape for verification. KV-based patient digital shift was derived by performing rigid registration between kV image and the digitally reconstructed radiography (DRR) to align the bony structure. This digital shift between kV-based and MV-based setup was defined as setup deviation. Results: Six sets of kV images were acquired for breast patients. The mean setup deviation was 2.3mm, 2.2mm and 1.8mm for anterior-posterior, superior-inferior and left-right direction respectively. The average setup deviation magnitude was 4.3±1.7mm for six patients. Patient with large breast had a larger setup deviation (4.4–6.2mm). There was no strong correlation between MV-based shift and setup deviation. Conclusion: A preliminary clinical workflow for kV-based whole breast radiation setup was established and tested. We observed setup deviation of the magnitude below than 5mm. With the benefit of providing higher contrast and MLC block overlaid on the images for treatment field verification, it is feasible to use kV imaging for breast patient setup.

  3. Nanovesicle-targeted Kv1.3 knockdown in memory T cells suppresses CD40L expression and memory phenotype.

    PubMed

    Chimote, Ameet A; Hajdu, Peter; Kottyan, Leah C; Harley, John B; Yun, Yeoheung; Conforti, Laura

    2016-05-01

    Ca(2+) signaling controls activation and effector functions of T lymphocytes. Ca(2+) levels also regulate NFAT activation and CD40 ligand (CD40L) expression in T cells. CD40L in activated memory T cells binds to its cognate receptor, CD40, on other cell types resulting in the production of antibodies and pro-inflammatory mediators. The CD40L/CD40 interaction is implicated in the pathogenesis of autoimmune disorders and CD40L is widely recognized as a therapeutic target. Ca(2+) signaling in T cells is regulated by Kv1.3 channels. We have developed lipid nanoparticles that deliver Kv1.3 siRNAs (Kv1.3-NPs) selectively to CD45RO(+) memory T cells and reduce the activation-induced Ca(2+) influx. Herein we report that Kv1.3-NPs reduced NFAT activation and CD40L expression exclusively in CD45RO(+) T cells. Furthermore, Kv1.3-NPs suppressed cytokine release and induced a phenotype switch of T cells from predominantly memory to naïve. These findings indicate that Kv1.3-NPs operate as targeted immune suppressive agents with promising therapeutic potentials.

  4. Sensory Neuron Downregulation of the Kv9.1 Potassium Channel Subunit Mediates Neuropathic Pain following Nerve Injury

    PubMed Central

    Tsantoulas, Christoforos; Zhu, Lan; Shaifta, Yasin; Grist, John; Ward, Jeremy P. T.; Raouf, Ramin; Michael, Gregory J.; McMahon, Stephen B.

    2013-01-01

    Chronic neuropathic pain affects millions of individuals worldwide, is typically long-lasting, and remains poorly treated with existing therapies. Neuropathic pain arising from peripheral nerve lesions is known to be dependent on the emergence of spontaneous and evoked hyperexcitability in damaged nerves. Here, we report that the potassium channel subunit Kv9.1 is expressed in myelinated sensory neurons, but is absent from small unmyelinated neurons. Kv9.1 expression was strongly and rapidly downregulated following axotomy, with a time course that matches the development of spontaneous activity and pain hypersensitivity in animal models. Interestingly, siRNA-mediated knock-down of Kv9.1 in naive rats led to neuropathic pain behaviors. Diminished Kv9.1 function also augmented myelinated sensory neuron excitability, manifested as spontaneous firing, hyper-responsiveness to stimulation, and persistent after-discharge. Intracellular recordings from ex vivo dorsal root ganglion preparations revealed that Kv9.1 knock-down was linked to lowered firing thresholds and increased firing rates under physiologically relevant conditions of extracellular potassium accumulation during prolonged activity. Similar neurophysiological changes were detected in animals subjected to traumatic nerve injury and provide an explanation for neuropathic pain symptoms, including poorly understood conditions such as hyperpathia and paresthesias. In summary, our results demonstrate that Kv9.1 dysfunction leads to spontaneous and evoked neuronal hyperexcitability in myelinated fibers, coupled with development of neuropathic pain behaviors. PMID:23197740

  5. Kv1.3 channel-blocking immunomodulatory peptides from parasitic worms: implications for autoimmune diseases

    PubMed Central

    Chhabra, Sandeep; Chang, Shih Chieh; Nguyen, Hai M.; Huq, Redwan; Tanner, Mark R.; Londono, Luz M.; Estrada, Rosendo; Dhawan, Vikas; Chauhan, Satendra; Upadhyay, Sanjeev K.; Gindin, Mariel; Hotez, Peter J.; Valenzuela, Jesus G.; Mohanty, Biswaranjan; Swarbrick, James D.; Wulff, Heike; Iadonato, Shawn P.; Gutman, George A.; Beeton, Christine; Pennington, Michael W.; Norton, Raymond S.; Chandy, K. George

    2014-01-01

    The voltage-gated potassium (Kv) 1.3 channel is widely regarded as a therapeutic target for immunomodulation in autoimmune diseases. ShK-186, a selective inhibitor of Kv1.3 channels, ameliorates autoimmune diseases in rodent models, and human phase 1 trials of this agent in healthy volunteers have been completed. In this study, we identified and characterized a large family of Stichodactyla helianthus toxin (ShK)–related peptides in parasitic worms. Based on phylogenetic analysis, 2 worm peptides were selected for study: AcK1, a 51-residue peptide expressed in the anterior secretory glands of the dog-infecting hookworm Ancylostoma caninum and the human-infecting hookworm Ancylostoma ceylanicum, and BmK1, the C-terminal domain of a metalloprotease from the filarial worm Brugia malayi. These peptides in solution adopt helical structures closely resembling that of ShK. At doses in the nanomolar–micromolar range, they block native Kv1.3 in human T cells and cloned Kv1.3 stably expressed in L929 mouse fibroblasts. They preferentially suppress the proliferation of rat CCR7− effector memory T cells without affecting naive and central memory subsets and inhibit the delayed-type hypersensitivity (DTH) response caused by skin-homing effector memory T cells in rats. Further, they suppress IFNγ production by human T lymphocytes. ShK-related peptides in parasitic worms may contribute to the potential beneficial effects of probiotic parasitic worm therapy in human autoimmune diseases.—Chhabra, S., Chang, S. C., Nguyen, H. M., Huq, R., Tanner, M. R., Londono, L. M., Estrada, R., Dhawan, V., Chauhan, S., Upadhyay, S. K., Gindin, M., Hotez, P. J., Valenzuela, J. G., Mohanty, B., Swarbrick, J. D., Wulff, H., Iadonato, S. P., Gutman, G. A., Beeton, C., Pennington, M. W., Norton, R. S., Chandy, K. G. Kv1.3 channel-blocking immunomodulatory peptides from parasitic worms: implications for autoimmune diseases. PMID:24891519

  6. Automated manual transmission controller

    DOEpatents

    Lawrie, Robert E.; Reed, Jr., Richard G.; Bernier, David R.

    1999-12-28

    A powertrain system for a hybrid vehicle. The hybrid vehicle includes a heat engine, such as a diesel engine, and an electric machine, which operates as both an electric motor and an alternator, to power the vehicle. The hybrid vehicle also includes a manual-style transmission configured to operate as an automatic transmission from the perspective of the driver. The engine and the electric machine drive an input shaft which in turn drives an output shaft of the transmission. In addition to driving the transmission, the electric machine regulates the speed of the input shaft in order to synchronize the input shaft during either an upshift or downshift of the transmission by either decreasing or increasing the speed of the input shaft. When decreasing the speed of the input shaft, the electric motor functions as an alternator to produce electrical energy which may be stored by a storage device. Operation of the transmission is controlled by a transmission controller which receives input signals and generates output signals to control shift and clutch motors to effect smooth launch, upshift shifts, and downshifts of the transmission, so that the transmission functions substantially as an automatic transmission from the perspective of the driver, while internally substantially functioning as a manual transmission.

  7. Bordetella pertussis transmission.

    PubMed

    Trainor, Elizabeth A; Nicholson, Tracy L; Merkel, Tod J

    2015-11-01

    Bordetella pertussis and B. bronchiseptica are Gram-negative bacterial respiratory pathogens. Bordetella pertussis is the causative agent of whooping cough and is considered a human-adapted variant of B. bronchiseptica. Bordetella pertussis and B. bronchiseptica share mechanisms of pathogenesis and are genetically closely related. However, despite the close genetic relatedness, these Bordetella species differ in several classic fundamental aspects of bacterial pathogens such as host range, pathologies and persistence. The development of the baboon model for the study of B. pertussis transmission, along with the development of the swine and mouse model for the study of B. bronchiseptica, has enabled the investigation of different aspects of transmission including the route, attack rate, role of bacterial and host factors, and the impact of vaccination on transmission. This review will focus on B. pertussis transmission and how animal models of B. pertussis transmission and transmission models using the closely related B. bronchiseptica have increased our understanding of B. pertussis transmission.

  8. Bordetella pertussis transmission.

    PubMed

    Trainor, Elizabeth A; Nicholson, Tracy L; Merkel, Tod J

    2015-11-01

    Bordetella pertussis and B. bronchiseptica are Gram-negative bacterial respiratory pathogens. Bordetella pertussis is the causative agent of whooping cough and is considered a human-adapted variant of B. bronchiseptica. Bordetella pertussis and B. bronchiseptica share mechanisms of pathogenesis and are genetically closely related. However, despite the close genetic relatedness, these Bordetella species differ in several classic fundamental aspects of bacterial pathogens such as host range, pathologies and persistence. The development of the baboon model for the study of B. pertussis transmission, along with the development of the swine and mouse model for the study of B. bronchiseptica, has enabled the investigation of different aspects of transmission including the route, attack rate, role of bacterial and host factors, and the impact of vaccination on transmission. This review will focus on B. pertussis transmission and how animal models of B. pertussis transmission and transmission models using the closely related B. bronchiseptica have increased our understanding of B. pertussis transmission. PMID:26374235

  9. Fabrication and testing of the flexible transmission line to the TFTR neutral beam ion sources

    SciTech Connect

    Haughian, J.; Lou, K.; Byrns, R.; Fong, E.; Carrieri, J.

    1983-12-01

    The four Neutral Beam Injectors (NBI) on the TFTR Tokamak Test Cell (TTC) floor require twelve transmission lines to carry arc and filament power to the twelve ion sources from the basement. Also, the Neutral Beam Test Cell (NBTC) requires three lines but on the same floor through a wall. The same basic specifications apply: (1) center bundle operates at 120 kV with respect to the outer cables, (2) filament circuits at 6000 A, (3) arc circuits at 3000 A, (4) gradient grid, (5) accel grids in a quadrupole configuration, (6) multi wire control cable, (7) SF/sub 6/ environment, (7) flexible, (8) 36'' centerline bend radius and (9) hi-pot to 200 kV.

  10. Experimental research on Ku-band magnetically insulated transmission line oscillator

    NASA Astrophysics Data System (ADS)

    Jiang, Tao; Zhang, Jiande; He, Juntao; Li, Zhiqiang; Ling, Junpu

    2015-10-01

    An improved Ku-band magnetically insulated transmission line oscillator is proposed and investigated experimentally. In the particle-in-cell simulation, the Ku-band MILO generates the microwave with a power of 1.62 GW and a frequency of 13 GHz at the input voltage of 474 kV. The device is fabricated based on the simulation results, and an experiment system is designed. In the preliminary experiments, output microwave with frequency of 13.02 GHz, power of 150 MW, and pulse width of 17 ns is generated, under the diode voltage of 450 kV. Analysis on the experiment results shows that plasma produced due to the large current hitting to the outside of the collection tank is the essential cause for the low amplitude of the microwave power and short pulse width.

  11. Measurement of the dielectric function of α-Al2O3 by transmission electron microscopy - Electron energy-loss spectroscopy without Cerenkov radiation effects.

    PubMed

    Sakaguchi, Norihito; Tanda, Luka; Kunisada, Yuji

    2016-10-01

    The dielectric function of α-Al2O3 was measured by electron energy-loss spectroscopy (EELS) coupled with the difference method. The influence of Cerenkov radiation was significant in measurements using a 200kV transmission electron microscope (TEM) and the correct dielectric function could not be obtained using the conventional EELS procedure. However, a good agreement between the optical data and EELS for the dielectric functions was obtained via a 60kV TEM. Combining EELS and the difference method, however, provided an accurate measurement of the dielectric function for α-Al2O3 even at an accelerating voltage of 200kV. The combination of EELS and the difference method in the nano-beam diffraction mode could derive an accurate dielectric function with superior spatial resolution regardless of the occurrence of Cerenkov radiation. PMID:27448199

  12. Measurement of the dielectric function of α-Al2O3 by transmission electron microscopy - Electron energy-loss spectroscopy without Cerenkov radiation effects.

    PubMed

    Sakaguchi, Norihito; Tanda, Luka; Kunisada, Yuji

    2016-10-01

    The dielectric function of α-Al2O3 was measured by electron energy-loss spectroscopy (EELS) coupled with the difference method. The influence of Cerenkov radiation was significant in measurements using a 200kV transmission electron microscope (TEM) and the correct dielectric function could not be obtained using the conventional EELS procedure. However, a good agreement between the optical data and EELS for the dielectric functions was obtained via a 60kV TEM. Combining EELS and the difference method, however, provided an accurate measurement of the dielectric function for α-Al2O3 even at an accelerating voltage of 200kV. The combination of EELS and the difference method in the nano-beam diffraction mode could derive an accurate dielectric function with superior spatial resolution regardless of the occurrence of Cerenkov radiation.

  13. Control design for SVC`s on the Mead-Adelanto and Mead-Phoenix Transmission Project

    SciTech Connect

    Larsen, E.V.; Clark, K.; Hill, A.T.; Piwko, R.J.; Beshir, M.J.; Bhuiyan, M.; Hormozi, F.J.; Braun, K.

    1996-07-01

    A major project is under construction to increase the capability of the 500 kV transmission system between Arizona and Southern California. This project includes two 388 Mvar SVC`s, which are needed primarily to stabilize power oscillations across the interface. The control system for these SVC`s includes some new concepts to accomplish this stabilizing influence. This paper describes the important features of this control system, including the main design considerations.

  14. A family of delayed rectifier Kv1 cDNAs showing cell type-specific expression in the squid stellate ganglion/giant fiber lobe complex.

    PubMed

    Rosenthal, J J; Liu, T I; Gilly, W F

    1997-07-01

    Squid giant axons are formed by giant fiber lobe (GFL) neurons of the stellate ganglion (SG). Other large motoneurons in the SG form a parallel system. A small family of cDNAs (SqKv1A-D) encoding Kv1 alpha-subunits was identified in a squid (Loligo opalescens) SG/GFL library. Members have distinct 5' untranslated regions (UTRs) and initial coding regions, but beyond a certain point (nucleotide 34 of SqKv1A) only nine differences exist. 3' UTRs are identical. Predicted alpha-subunits are nearly identical, and only the N termini differ significantly, primarily in length. RNase protection assays that use RNA isolated from specific SG regions show that SqKv1A mRNA is expressed prominently in the GFL but not in the SG proper. SqKv1B yields the opposite pattern. SqKv1D also is expressed only in the SG. SqKv1C expression was not detectable. In situ hybridizations confirm these results and reveal that SqKv1B mRNA is abundant in many large neurons of the SG, whereas SqKv1D expression is limited to small isolated clusters of neurons. SqKv1A and B are thus the predominant Kv1 mRNAs in the SG/GFL complex. Activation properties of SqKv1A and B channels expressed in oocytes are very similar to one another and compare favorably with properties of native delayed rectifier channels in GFL neurons and large SG neurons. The Kv1 complement in these squid neurons thus seems to be relatively simple. Several differences exist between cloned and native channels, however, and may reflect differences in the cellular environments of oocytes and neurons.

  15. Deletion of Kvβ1.1 subunit leads to electrical and haemodynamic changes causing cardiac hypertrophy in female murine hearts

    PubMed Central

    Tur, Jared; Chapalamadugu, Kalyan C.; Padawer, Timothy; Badole, Sachin L.; Kilfoil, Peter J.; Bhatnagar, Aruni; Tipparaju, Srinivas M.

    2016-01-01

    Cardiovascular disease is the leading cause of death and debility in women in the USA, and cardiac arrhythmias are a major concern. Voltage-gated potassium (Kv) channels along with the binding partners; Kvβ subunits are major regulators of the action potential (AP) shape and duration (APD). The regulation of Kv channels by the Kvβ1 subunit is unknown in female hearts. In the present study, we hypothesized that the Kvβ1 subunit is an important regulator of female cardiac physiology. To test this hypothesis, we ablated (knocked out; KO) the KCNAB1 isoform 1 (Kvβ1.1) subunit in mice and evaluated cardiac function and electrical activity by using ECG, monophasic action potential recordings and echocardiography. Our results showed that the female Kvβ1.1 KO mice developed cardiac hypertrophy, and the hearts were structurally different, with enlargement and increased area. The electrical derangements caused by Kvβ1.1 KO in female mice included long QTc and QRS intervals along with increased APD (APD20–90% repolarization). The male Kvβ1.1 KO mice did not develop cardiac hypertrophy, but they showed long QTc and prolonged APD. Molecular analysis showed that several genes that support cardiac hypertrophy were significantly altered in Kvβ1.1 KO female hearts. In particular, myosin heavy chain αexpression was significantly elevated in Kvβ1.1 KO mouse heart. Using a small interfering RNA strategy, we identified that knockdown of Kvβ1 increases myosin heavy chain αexpression in H9C2 cells. Collectively, changes in molecular and cell signalling pathways clearly point towards a distinct electrical and structural remodelling consistent with cardiac hypertrophy in the Kvβ1.1 KO female mice. PMID:27038296

  16. Subtype-selective activation of K(v)7 channels by AaTXKβ₂₋₆₄, a novel toxin variant from the Androctonus australis scorpion venom.

    PubMed

    Landoulsi, Zied; Miceli, Francesco; Palmese, Angelo; Amoresano, Angela; Marino, Gennaro; El Ayeb, Mohamed; Taglialatela, Maurizio; Benkhalifa, Rym

    2013-11-01

    K(v)7.4 channel subunits are expressed in central auditory pathways and in inner ear sensory hair cells and skeletal and smooth muscle cells. Openers of K(v)7.4 channels have been suggested to improve hearing loss, systemic or pulmonary arterial hypertension, urinary incontinence, gastrointestinal and neuropsychiatric diseases, and skeletal muscle disorders. Scorpion venoms are a large source of peptides active on K⁺ channels. Therefore, we have optimized a combined purification/screening procedure to identify specific modulator(s) of K(v)7.4 channels from the venom of the North African scorpion Androctonus australis (Aa). We report the isolation and functional characterization of AaTXKβ₂₋₆₄, a novel variant of AaTXKβ₁₋₆₄, in a high-performance liquid chromatography fraction from Aa venom (named P8), which acts as the first peptide activator of K(v)7.4 channels. In particular, in both Xenopus oocytes and mammalian Chinese hamster ovary cells, AaTXKβ₂₋₆₄, but not AaTXKβ₁₋₆₄, hyperpolarized the threshold voltage of current activation and increased the maximal currents of heterologously expressed K(v)7.4 channels. AaTXKβ₂₋₆₄ also activated K(v)7.3, K(v)7.2/3, and K(v)7.5/3 channels, whereas homomeric K(v)1.1, K(v)7.1, and K(v)7.2 channels were unaffected. We anticipate that these results may prove useful in unraveling the novel biologic roles of AaTXKβ₂₋₆₄-sensitive K(v)7 channels and developing novel pharmacologic tools that allow subtype-selective targeting of K(v)7 channels. PMID:24019223

  17. Transmission Planning Analysis Tool

    SciTech Connect

    2015-06-23

    Developed to solve specific problem: Assist transmission planning for regional transfers in interconnected power systems. This work was originated in a study for the U.S. Department of State, to recommend transmission reinforcements for the Central American regional system that interconnects 6 countries. Transmission planning analysis is currently performed by engineers with domainspecific and systemspecific knowledge without a unique methodology. The software codes of this disclosure assists engineers by defining systematic analysis procedures to help identify weak points and make decisions on transmission planning of regional interconnected power systems. Transmission Planning Analysis Tool groups PSS/E results of multiple AC contingency analysis and voltage stability analysis and QV analysis of many scenarios of study and arrange them in a systematic way to aid power system planning engineers or transmission operators in effective decision]making process or in the off]line study environment.

  18. Transmission Planning Analysis Tool

    2015-06-23

    Developed to solve specific problem: Assist transmission planning for regional transfers in interconnected power systems. This work was originated in a study for the U.S. Department of State, to recommend transmission reinforcements for the Central American regional system that interconnects 6 countries. Transmission planning analysis is currently performed by engineers with domainspecific and systemspecific knowledge without a unique methodology. The software codes of this disclosure assists engineers by defining systematic analysis procedures to help identifymore » weak points and make decisions on transmission planning of regional interconnected power systems. Transmission Planning Analysis Tool groups PSS/E results of multiple AC contingency analysis and voltage stability analysis and QV analysis of many scenarios of study and arrange them in a systematic way to aid power system planning engineers or transmission operators in effective decision]making process or in the off]line study environment.« less

  19. Series Transmission Line Transformer

    DOEpatents

    Buckles, Robert A.; Booth, Rex; Yen, Boris T.

    2004-06-29

    A series transmission line transformer is set forth which includes two or more of impedance matched sets of at least two transmissions lines such as shielded cables, connected in parallel at one end ans series at the other in a cascading fashion. The cables are wound about a magnetic core. The series transmission line transformer (STLT) which can provide for higher impedance ratios and bandwidths, which is scalable, and which is of simpler design and construction.

  20. Understanding Ebola Virus Transmission

    PubMed Central

    Judson, Seth; Prescott, Joseph; Munster, Vincent

    2015-01-01

    An unprecedented number of Ebola virus infections among healthcare workers and patients have raised questions about our understanding of Ebola virus transmission. Here, we explore different routes of Ebola virus transmission between people, summarizing the known epidemiological and experimental data. From this data, we expose important gaps in Ebola virus research pertinent to outbreak situations. We further propose experiments and methods of data collection that will enable scientists to fill these voids in our knowledge about the transmission of Ebola virus. PMID:25654239

  1. Cellular Mechanism of Inner Ear Genetic Disease, roles of Kv7.1 (KCNQ1) Channel

    NASA Astrophysics Data System (ADS)

    Mousavi Nik, Atefeh

    Potassium channels are the most diverse and widely distributed membrane protein in all living organisms. They have various roles in the body such as controlling membrane potential, cell volume, and cell migration. Many studies have shown that mutation in these channels is associated with different diseases for example: Hearing Defect, Cardiac Arrhythmia, Episodic Ataxia, Seizure and Neuromyotonia. One of the most important diseases associated with K+ channel mutations is called Jervell and Lange-Nielsen syndrome (JLNS). This disease causes bilateral congenital deafness and the patients also suffer from Long QT and they usually experience syncopal episodes in their life and eventually die as a result of cardiac arrest. The gene KCNQ1 encodes the Kv7.1 voltage gated potassium channel. This channel expresses in apical membrane of marginal cell in stria vasularis of cochlea and secret K+ ion to endolymp to keep the endocochlear potential stable, which is necessary for the inner ear to function properly. Kv7.1 channel also expresses in cardiac myocytes and mutation in this gene is associated with another syndrome called Romano-Ward syndrome (RWS). Although Romano-Ward patients have mutation in KCNQ1, similar to Jervell and Lange-Nielsen patients, they only suffer from cardiac defect, and their hearing is completely normal. Several studies identified that mutations in Kv7.1 gene is associated with JLNS and RWS, but the biophysical and cellular mechanisms of these mutations are still unknown. To determine the cellular mechanisms of JLNS and RWS, and to provide mechanistic insight on the functional outputs of JLNS versus RWS mutations, we generated several mutant forms of the human Kv7.1 ( KCNQ1) clone, using site-directed mutagenesis to define their sub-cellular localization and examined their electrophysiological properties. We identified JLNS and RWS mutations at the S4-S5-linker, the pore loop (P-loop) and the C-terminus of hKv7.1 which have been found to control

  2. Distinct Kv Channel Subtypes Contribute to Differences in Spike Signaling Properties in the Axon Initial Segment and Presynaptic Boutons of Cerebellar Interneurons

    PubMed Central

    Rowan, Matthew J. M.; Tranquil, Elizabeth

    2014-01-01

    The discrete arrangement of voltage-gated K+ (Kv) channels in axons may impart functional advantages in action potential (AP) signaling yet, in compact cell types, the organization of Kv channels is poorly understood. We find that in cerebellar stellate cell interneurons of mice, the composition and influence of Kv channels populating the axon is diverse and depends on location allowing axonal compartments to differentially control APs in a local manner. Kv1 channels determine AP repolarization at the spike initiation site but not at more distal sites, limiting the expression of use-dependent spike broadening to the most proximal axon region, likely a key attribute informing spiking phenotype. Local control of AP repolarization at presynaptic boutons depends on Kv3 channels keeping APs brief, thus limiting Ca2+ influx and synaptic strength. These observations suggest that AP repolarization is tuned by the local influence of distinct Kv channel types, and this organization enhances the functional segregation of axonal compartments. PMID:24806686

  3. Elective automatic shift transmission

    SciTech Connect

    Redzinski, G.E.

    1986-09-02

    For use in vehicle of the type having an engine coupled with traction wheels through a driveline including a change-speed transmission, the transmission includes drive direction reversing means, a drive direction selector for manual control of the reversing means and having a forward and reverse position, the transmission including ratio changing means, a manual gear selector for operation of the ratio changing means for shifting the transmission into a selected gear, and control means responsive to a control signal for upshifting and downshifting between first and second gears.

  4. Nanometres-resolution Kikuchi patterns from materials science specimens with transmission electron forward scatter diffraction in the scanning electron microscope.

    PubMed

    Brodusch, N; Demers, H; Gauvin, R

    2013-04-01

    A charge-coupled device camera of an electron backscattered diffraction system in a scanning electron microscope was positioned below a thin specimen and transmission Kikuchi patterns were collected. Contrary to electron backscattered diffraction, transmission electron forward scatter diffraction provides phase identification and orientation mapping at the nanoscale. The minimum Pd particle size for which a Kikuchi diffraction pattern was detected and indexed reliably was 5.6 nm. An orientation mapping resolution of 5 nm was measured at 30 kV. The resolution obtained with transmission electron forward scatter diffraction was of the same order of magnitude than that reported in electron nanodiffraction in the transmission electron microscope. An energy dispersive spectrometer X-ray map and a transmission electron forward scatter diffraction orientation map were acquired simultaneously. The high-resolution chemical, phase and orientation maps provided at once information on the chemical form, orientation and coherency of precipitates in an aluminium-lithium 2099 alloy.

  5. Cooperativity between calmodulin-binding sites in Kv7.2 channels.

    PubMed

    Alaimo, Alessandro; Alberdi, Araitz; Gomis-Perez, Carolina; Fernández-Orth, Juncal; Gómez-Posada, Juan Camilo; Areso, Pilar; Villarroel, Alvaro

    2013-01-01

    Among the multiple roles assigned to calmodulin (CaM), controlling the surface expression of Kv7.2 channels by binding to two discontinuous sites is a unique property of this Ca(2+) binding protein. Mutations that interfere with CaM binding or the sequestering of CaM prevent this M-channel component from exiting the endoplasmic reticulum (ER), which reduces M-current density in hippocampal neurons, enhancing excitability and offering a rational mechanism to explain some forms of benign familial neonatal convulsions (BFNC). Previously, we identified a mutation (S511D) that impedes CaM binding while allowing the channel to exit the ER, hinting that CaM binding may not be strictly required for Kv7.2 channel trafficking to the plasma membrane. Alternatively, this interaction with CaM might escape detection and, indeed, we now show that the S511D mutant contains functional CaM-binding sites that are not detected by classical biochemical techniques. Surface expression and function is rescued by CaM, suggesting that free CaM in HEK293 cells is limiting and reinforcing the hypothesis that CaM binding is required for ER exit. Within the CaM-binding domain formed by two sites (helix A and helix B), we show that CaM binds to helix B with higher apparent affinity than helix A, both in the presence and absence of Ca(2+), and that the two sites cooperate. Hence, CaM can bridge two binding domains, anchoring helix A of one subunit to helix B of another subunit, in this way influencing the function of Kv7.2 channels.

  6. Transcriptional repression of the M channel subunit Kv7.2 in chronic nerve injury

    PubMed Central

    Rose, Kirstin; Ooi, Lezanne; Dalle, Carine; Robertson, Brian; Wood, Ian C.; Gamper, Nikita

    2011-01-01

    Neuropathic pain is a severe health problem for which there is a lack of effective therapy. A frequent underlying condition of neuropathic pain is a sustained overexcitability of pain-sensing (nociceptive) sensory fibres. Therefore, the identification of mechanisms for such abnormal neuronal excitability is of utmost importance for understanding neuropathic pain. Despite much effort, an inclusive model explaining peripheral overexcitability is missing. We investigated transcriptional regulation of the Kcnq2 gene, which encodes the Kv7.2 subunit of membrane potential-stabilizing M channel, in peripheral sensory neurons in a model of neuropathic pain—partial sciatic nerve ligation (PSNL). We show that Kcnq2 is the major Kcnq gene transcript in dorsal root ganglion (DRG); immunostaining and patch-clamp recordings from acute ganglionic slices verified functional expression of Kv7.2 in small-diameter nociceptive DRG neurons. Neuropathic injury induced substantial downregulation of Kv7.2 expression. Levels of repressor element 1–silencing transcription factor (REST), which is known to suppress Kcnq2 expression, were upregulated in response to neuropathic injury identifying the likely mechanism of Kcnq2 regulation. Behavioural experiments demonstrated that neuropathic hyperalgesia following PSNL developed faster than the downregulation of Kcnq2 expression could be detected, suggesting that this transcriptional mechanism may contribute to the maintenance rather than the initiation of neuropathic pain. Importantly, the decrease in the peripheral M channel abundance could be functionally compensated by peripherally applied M channel opener flupirtine, which alleviated neuropathic hyperalgesia. Our work suggests a novel mechanism for neuropathic overexcitability and brings focus on M channels and REST as peripheral targets for the treatment of neuropathic pain. Neuropathic injury induces transcriptional downregulation of the Kcnq2 potassium channel gene by the

  7. RBE of kV CBCT radiation determined by Monte Carlo DNA damage simulations.

    PubMed

    Kirkby, C; Ghasroddashti, E; Poirier, Y; Tambasco, M; Stewart, R D

    2013-08-21

    Due to the higher LET of kilovoltage (kV) radiation, there is potential for an increase in relative biological effectiveness (RBE) of absorbed doses of radiation from kV cone beam computed tomography (CBCT) sources in reference to megavoltage or Co-60 doses. This work develops a method for accurately coupling a Monte Carlo (MC) radiation transport code (PENELOPE) with the damage simulation (MCDS) to predict relative numbers of DNA double strand breaks (DSBs). The MCDS accounts for slowing down of electrons and delta ray production within the cell nucleus; however, determining the spectrum of electrons incident on the cell nucleus from photons interacting in a larger region of tissue is not trivial. PENELOPE simulations were conducted with a novel tally algorithm invoked where electrons incident on a detection material were tracked and both the incident energy and the final deposited dose were recorded. The DSB yield predicted by a set of MCDS runs of monoenergetic electrons was then looked up in a table and weighted by the specific energy of the incident electron. Our results indicate that the RBE for DSB induction is 1.1 for diagnostic x-rays with energies from 80 to 125 kVp. We found no significant change in RBE with depth or filtration. The predicted absolute DSB yields are about three times lower for cells irradiated under anoxic conditions than the yield in cells irradiated under normoxic (5%) or fully aerobic (100%) conditions. However, oxygen concentration has a negligible (± 0.02) effect on the RBE of kV CBCT x-rays.

  8. Collimated electron beam accelerated at 12 kV from a Penning discharge

    SciTech Connect

    Toader, D.; Oane, M.; Ticoş, C. M.

    2015-01-15

    A pulsed electron beam accelerated at 12 kV with a duration of 40 μs per pulse is obtained from a Penning discharge with a hollow anode and two cathodes. The electrons are extracted through a hole in one of the cathodes and focused by a pair of coils. The electron beam has a diameter of a few mm in the cross section, while the beam current reaches peak values of 400 mA, depending on the magnetic field inside the focussing coils. This relatively inexpensive and compact device is suitable for the irradiation of small material samples placed in high vacuum.

  9. Spectroscopic determination of the composition of a 50 kV hydrogen diagnostic neutral beam

    NASA Astrophysics Data System (ADS)

    Feng, X.; Nornberg, M. D.; Craig, D.; Den Hartog, D. J.; Oliva, S. P.

    2016-11-01

    A grating spectrometer with an electron multiplying charge-coupled device camera is used to diagnose a 50 kV, 5 A, 20 ms hydrogen diagnostic neutral beam. The ion source density is determined from Stark broadened Hβ emission and the spectrum of Doppler-shifted Hα emission is used to quantify the fraction of ions at full, half, and one-third beam energy under a variety of operating conditions including fueling gas pressure and arc discharge current. Beam current is optimized at low-density conditions in the ion source while the energy fractions are found to be steady over most operating conditions.

  10. WE-G-18A-02: Calibration-Free Combined KV/MV Short Scan CBCT

    SciTech Connect

    Wu, M; Loo, B; Bazalova, M; Fahrig, R; Star-Lack, J

    2014-06-15

    Purpose: To combine orthogonal kilo-voltage (kV) and Mega-voltage (MV) projection data for short scan cone-beam CT to reduce imaging time on current radiation treatment systems, using a calibration-free gain correction method. Methods: Combining two orthogonal projection data sets for kV and MV imaging hardware can reduce the scan angle to as small as 110° (90°+fan) such that the total scan time is ∼18 seconds, or within a breath hold. To obtain an accurate reconstruction, the MV projection data is first linearly corrected using linear regression using the redundant data from the start and end of the sinogram, and then the combined data is reconstructed using the FDK method. To correct for the different changes of attenuation coefficients in kV/MV between soft tissue and bone, the forward projection of the segmented bone and soft tissue from the first reconstruction in the redundant region are added to the linear regression model. The MV data is corrected again using the additional information from the segmented image, and combined with kV for a second FDK reconstruction. We simulated polychromatic 120 kVp (conventional a-Si EPID with CsI) and 2.5 MVp (prototype high-DQE MV detector) projection data with Poisson noise using the XCAT phantom. The gain correction and combined kV/MV short scan reconstructions were tested with head and thorax cases, and simple contrast-to-noise ratio measurements were made in a low-contrast pattern in the head. Results: The FDK reconstruction using the proposed gain correction method can effectively reduce artifacts caused by the differences of attenuation coefficients in the kV/MV data. The CNRs of the short scans for kV, MV, and kV/MV are 5.0, 2.6 and 3.4 respectively. The proposed gain correction method also works with truncated projections. Conclusion: A novel gain correction and reconstruction method was developed to generate short scan CBCT from orthogonal kV/MV projections. This work is supported by NIH Grant 5R01CA138426-05.

  11. Accelerated aging and flashover tests on 138 kV nonceramic line post insulators

    SciTech Connect

    Schneider, H.M.; Guidi, W.W. ); Burnham, J.T. ); Gorur, R.S. ); Hall, J.F. )

    1993-01-01

    The behavior of 138 kV nonceramic line post insulators is investigated by means of clean fog tests conducted before and after aging in a specially designed accelerated aging chamber. The laboratory aging cycles are justified on the basis of actual weather in the coastal regions of Florida. Analytical measurements quantifying the degree of artificial aging are discussed and comparisons of artificial aging with service experience are presented. Observations of audible noise and radio influence voltage during the clean fog tests are reported.

  12. Long term pre-qualification testing program on a 230kV XLPE cable system

    SciTech Connect

    Champion, T.C.; Agostinelli, F.M.; Rosevear, R.D.

    1994-12-31

    this paper describes the installation, testing, and results of a long term, full scale laboratory evaluation of a 230kV XLPE insulated cable system. System components included two innovative, pre-molded splices a 128 meter (420 foot) cable run, and two silicone oil filled, porcelain cable terminations. Load cycle aging was performed on the cable system over a four year period. After successfully completing the outdoor aging program, the system was exposed to a final impulses breakdown test. Results demonstrated the importance of considering thermomechanical bending in aluminum conductor, XLPE insulated designs. The influence on cable ampacity of solar heating at riser transitions was also demonstrated.

  13. Long term pre-qualification testing program on a 230kV XLPE cable system

    SciTech Connect

    Champion, T.C.; Agostinelli, F.M.; Rosevear, R.D.

    1995-01-01

    This paper describes the installation, testing, and results of a long term, full scale laboratory evaluation of a 230kV XLPE insulated cable system. System components included two innovative, pre-molded splices, a 128 meter (420 foot) cable run, and two silicone oil filled, porcelain cable terminations. Load cycle aging was performed on the cable system over a four year period. After successfully completing the outdoor aging program, the system was exposed to a final impulse breakdown test. Results demonstrated the importance or considering thermomechanical bending in aluminum conductor, XLPE insulated designs. The influence on cable ampacity of solar beating at riser transitions was also demonstrated.

  14. Collimated electron beam accelerated at 12 kV from a Penning discharge.

    PubMed

    Toader, D; Oane, M; Ticoş, C M

    2015-01-01

    A pulsed electron beam accelerated at 12 kV with a duration of 40 μs per pulse is obtained from a Penning discharge with a hollow anode and two cathodes. The electrons are extracted through a hole in one of the cathodes and focused by a pair of coils. The electron beam has a diameter of a few mm in the cross section, while the beam current reaches peak values of 400 mA, depending on the magnetic field inside the focussing coils. This relatively inexpensive and compact device is suitable for the irradiation of small material samples placed in high vacuum.

  15. Design and development of a 5 kV isolated solid state switch

    NASA Technical Reports Server (NTRS)

    Holbrook, R. J.; Scapple, R. Y.; Keister, F. Z.; Gooder, S. T.

    1975-01-01

    This paper describes the design and fabrication of a 5000 volt isolated hybrid switch developed by Hughes Aircraft Company under contract to NASA/Lewis. Hughes did the packaging design and NASA did the circuit design. This unique microcircuit is intended for use as a shorting switch for large extraterrestrial solar cell arrays. The packaging design for the 5 kV isolated hybrid switch is different from most hybrid microcircuits in that it utilizes a compartmentalized plastic case (a portion of which is encapsulated), is not hermetic, and is designed for high voltage operation.

  16. Metrological traceability for AC High-Voltage in Inmetro up to 40 kV

    NASA Astrophysics Data System (ADS)

    Vitorio, P. C. O.; de Lima, V. R.; Borges Filho, O.; de Souza, L. A. A.; Asencios, O. W. G.

    2016-07-01

    This paper refers to a project carried out in Inmetro aiming to provide internal metrological traceability for 60 Hz AC High-Voltage up to 40 kV. It presents details about the method used, its equations and obtained results. A capacitance and tanb bridge, with a built-in current comparator, was used in combination with two standard capacitors to calibrate a standard potential transformer (PT), both in ratio and phase angle. The results obtained by Inmetro showed good agreement with PTB ones, for the same PT. The maximum estimated uncertainty was 0,0049% for ratio error and 104 μrad for phase angle error.

  17. The Scorpion Toxin Analogue BmKTX-D33H as a Potential Kv1.3 Channel-Selective Immunomodulator for Autoimmune Diseases

    PubMed Central

    Ye, Fang; Hu, Youtian; Yu, Weiwei; Xie, Zili; Hu, Jun; Cao, Zhijian; Li, Wenxin; Wu, Yingliang

    2016-01-01

    The Kv1.3 channel-acting scorpion toxins usually adopt the conserved anti-parallel β-sheet domain as the binding interface, but it remains challenging to discover some highly selective Kv1.3 channel-acting toxins. In this work, we investigated the pharmacological profile of the Kv1.3 channel-acting BmKTX-D33H, a structural analogue of the BmKTX scorpion toxin. Interestingly, BmKTX-D33H, with its conserved anti-parallel β-sheet domain as a Kv1.3 channel-interacting interface, exhibited more than 1000-fold selectivity towards the Kv1.3 channel as compared to other K+ channels (including Kv1.1, Kv1.2, Kv1.7, Kv11.1, KCa2.2, KCa2.3, and KCa3.1). As expected, BmKTX-D33H was found to inhibit the cytokine production and proliferation of both Jurkat cells and human T cells in vitro. It also significantly improved the delayed-type hypersensitivity (DTH) responses, an autoreactive T cell-mediated inflammation in rats. Amino acid sequence alignment and structural analysis strongly suggest that the “evolutionary” Gly11 residue of BmKTX-D33H interacts with the turret domain of Kv1 channels; it appears to be a pivotal amino acid residue with regard to the selectivity of BmKTX-D33H towards the Kv1.3 channel (in comparison with the highly homologous scorpion toxins). Together, our data indicate that BmKTX-D33H is a Kv1.3 channel–specific blocker. Finally, the remarkable selectivity of BmKTX-D33H highlights the great potential of evolutionary-guided peptide drug design in future studies. PMID:27104568

  18. The Scorpion Toxin Analogue BmKTX-D33H as a Potential Kv1.3 Channel-Selective Immunomodulator for Autoimmune Diseases.

    PubMed

    Ye, Fang; Hu, Youtian; Yu, Weiwei; Xie, Zili; Hu, Jun; Cao, Zhijian; Li, Wenxin; Wu, Yingliang

    2016-04-01

    The Kv1.3 channel-acting scorpion toxins usually adopt the conserved anti-parallel β-sheet domain as the binding interface, but it remains challenging to discover some highly selective Kv1.3 channel-acting toxins. In this work, we investigated the pharmacological profile of the Kv1.3 channel-acting BmKTX-D33H, a structural analogue of the BmKTX scorpion toxin. Interestingly, BmKTX-D33H, with its conserved anti-parallel β-sheet domain as a Kv1.3 channel-interacting interface, exhibited more than 1000-fold selectivity towards the Kv1.3 channel as compared to other K⁺ channels (including Kv1.1, Kv1.2, Kv1.7, Kv11.1, KCa2.2, KCa2.3, and KCa3.1). As expected, BmKTX-D33H was found to inhibit the cytokine production and proliferation of both Jurkat cells and human T cells in vitro. It also significantly improved the delayed-type hypersensitivity (DTH) responses, an autoreactive T cell-mediated inflammation in rats. Amino acid sequence alignment and structural analysis strongly suggest that the "evolutionary" Gly11 residue of BmKTX-D33H interacts with the turret domain of Kv1 channels; it appears to be a pivotal amino acid residue with regard to the selectivity of BmKTX-D33H towards the Kv1.3 channel (in comparison with the highly homologous scorpion toxins). Together, our data indicate that BmKTX-D33H is a Kv1.3 channel-specific blocker. Finally, the remarkable selectivity of BmKTX-D33H highlights the great potential of evolutionary-guided peptide drug design in future studies. PMID:27104568

  19. Localization and function of the Kv3.1b subunit in the rat medulla oblongata: focus on the nucleus tractus solitarii

    PubMed Central

    Dallas, Mark L; Atkinson, Lucy; Milligan, Carol J; Morris, Neil P; Lewis, David I; Deuchars, Susan A; Deuchars, Jim

    2005-01-01

    The voltage-gated potassium channel subunit Kv3.1 confers fast firing characteristics to neurones. Kv3.1b subunit immunoreactivity (Kv3.1b-IR) was widespread throughout the medulla oblongata, with labelled neurones in the gracile, cuneate and spinal trigeminal nuclei. In the nucleus of the solitary tract (NTS), Kv3.1b-IR neurones were predominantly located close to the tractus solitarius (TS) and could be GABAergic or glutamatergic. Ultrastructurally, Kv3.1b-IR was detected in NTS terminals, some of which were vagal afferents. Whole-cell current-clamp recordings from neurones near the TS revealed electrophysiological characteristics consistent with the presence of Kv3.1b subunits: short duration action potentials (4.2 ± 1.4 ms) and high firing frequencies (68.9 ± 5.3 Hz), both sensitive to application of TEA (0.5 mm) and 4-aminopyridine (4-AP; 30 μm). Intracellular dialysis of an anti-Kv3.1b antibody mimicked and occluded the effects of TEA and 4-AP in NTS and dorsal column nuclei neurones, but not in dorsal vagal nucleus or cerebellar Purkinje cells (which express other Kv3 subunits, but not Kv3.1b). Voltage-clamp recordings from outside-out patches from NTS neurones revealed an outward K+ current with the basic characteristics of that carried by Kv3 channels. In NTS neurones, electrical stimulation of the TS evoked EPSPs and IPSPs, and TEA and 4-AP increased the average amplitude and decreased the paired pulse ratio, consistent with a presynaptic site of action. Synaptic inputs evoked by stimulation of a region lacking Kv3.1b-IR neurones were not affected, correlating the presence of Kv3.1b in the TS with the pharmacological effects. PMID:15528247

  20. SU-E-J-31: Monitor Interfractional Variation of Tumor Respiratory Motion Using 4D KV Conebeam Computed Tomography for Stereotactic Body Radiation Therapy of Lung Cancer

    SciTech Connect

    Tai, A; Prior, P; Gore, E; Johnstone, C; Li, X

    2015-06-15

    Purpose: 4DCT has been widely used to generate internal tumor volume (ITV) for a lung tumor for treatment planning. However, lung tumors may show different respiratory motion on the treatment day. The purpose of this study is to evaluate 4D KV conebeam computed tomography (CBCT) for monitoring tumor interfractional motion variation between simulation and each fraction of stereotactic body radiation therapy (SBRT) for lung cancer. Methods: 4D KV CBCT was acquired with the Elekta XVI system. The accuracy of 4D KV CBCT for image-guided radiation therapy (IGRT) was tested with a dynamic thorax motion phantom (CIRS, Virginia) with a linear amplitude of 2 cm. In addition, an adult anthropomorphic phantom (Alderson, Rando) with optically stimulated luminescence (OSL) dosimeters embedded at the center and periphery of a slab of solid water was used to measure the dose of 4D KV CBCT and to compare it with the dose with 3D KV CBCT. The image registration was performed by aligning\\ each phase images of 4D KV CBCT to the planning images and the final couch shifts were calculated as a mean of all these individual shifts along each direction.A workflow was established based on these quality assurance tests for lung cancer patients. Results: 4D KV CBCT does not increase imaging dose in comparison to 3D KV CBCT. Acquisition of 4D KV CBCT is 4 minutes as compared to 2 minutes for 3D KV CBCT. Most of patients showed a small daily variation of tumor respiratory motion about 2 mm. However, some patients may have more than 5 mm variations of tumor respiratory motion. Conclusion: The radiation dose does not increase with 4D KV CBCT. 4D KV CBCT is a useful tool for monitoring interfractional variations of tumor respiratory motion before SBRT of lung cancer patients.

  1. New pyrimido-indole compound CD-160130 preferentially inhibits the KV11.1B isoform and produces antileukemic effects without cardiotoxicity.

    PubMed

    Gasparoli, Luca; D'Amico, Massimo; Masselli, Marika; Pillozzi, Serena; Caves, Rachel; Khuwaileh, Rawan; Tiedke, Wolfgang; Mugridge, Kenneth; Pratesi, Alessandro; Mitcheson, John S; Basso, Giuseppe; Becchetti, Andrea; Arcangeli, Annarosa

    2015-02-01

    KV11.1 (hERG1) channels are often overexpressed in human cancers. In leukemias, KV11.1 regulates pro-survival signals that promote resistance to chemotherapy, raising the possibility that inhibitors of KV11.1 could be therapeutically beneficial. However, because of the role of KV11.1 in cardiac repolarization, blocking these channels may cause cardiac arrhythmias. We show that CD-160130, a novel pyrimido-indole compound, blocks KV11.1 channels with a higher efficacy for the KV11.1 isoform B, in which the IC50 (1.8 μM) was approximately 10-fold lower than observed in KV11.1 isoform A. At this concentration, CD-160130 also had minor effects on Kir2.1, KV 1.3, Kv1.5, and KCa3.1. In vitro, CD-160130 induced leukemia cell apoptosis, and could overcome bone marrow mesenchymal stromal cell (MSC)-induced chemoresistance. This effect was caused by interference with the survival signaling pathways triggered by MSCs. In vivo, CD-160130 produced an antileukemic activity, stronger than that caused by cytarabine. Consistent with its atypical target specificity, CD-160130 did not bind to the main binding site of the arrhythmogenic KV11.1 blockers (the Phe656 pore residue). Importantly, in guinea pigs CD-160130 produced neither alteration of the cardiac action potential shape in dissociated cardiomyocytes nor any lengthening of the QT interval in vivo. Moreover, CD-160130 had no myelotoxicity on human bone marrow-derived cells. Therefore, CD-160130 is a promising first-in-class compound to attempt oncologic therapy without cardiotoxicity, based on targeting KV11.1. Because leukemia and cardiac cells tend to express different ratios of the A and B KV11.1 isoforms, the pharmacological properties of CD-160130 may depend, at least in part, on isoform specificity. PMID:25411366

  2. EXPRESSION AND DISTRIBUTION OF Kv4 POTASSIUM CHANNEL SUBUNITS AND POTASSIUM CHANNEL INTERACTING PROTEINS IN SUBPOPULATIONS OF INTERNEURONS IN THE BASOLATERAL AMYGDALA

    PubMed Central

    DABROWSKA, J.; RAINNIE, D. G.

    2010-01-01

    Kv4 potassium channel α subunits, Kv4.1, Kv4.2, and Kv4.3, determine some of the fundamental physiological properties of neurons in the CNS. Kv4 subunits are associated with auxiliary β-subunits, such as the potassium channel interacting proteins (KChIP1 – 4), which are thought to regulate the trafficking and gating of native Kv4 potassium channels. Intriguingly, KChIP1 is thought to show cell type-selective expression in GABA-ergic inhibitory interneurons, while other β-subunits (KChIP2–4) are associated with principal glutamatergic neurons. However, nothing is known about the expression of Kv4 family α- and β-subunits in specific interneurons populations in the BLA. Here, we have used immunofluorescence, co-immunoprecipitation, and Western Blotting to determine the relative expression of KChIP1 in the different interneuron subtypes within the BLA, and its co-localization with one or more of the Kv4 α subunits. We show that all three α-subunits of Kv4 potassium channel are found in rat BLA neurons, and that the immuno-reactivity of KChIP1 closely resembles that of Kv4.3. Indeed, Kv4.3 showed almost complete co-localization with KChIP1 in the soma and dendrites of a distinct subpopulation of BLA neurons. Dual-immunofluorescence studies revealed this to be in BLA interneurons immunoreactive for parvalbumin, cholecystokin-8, and somatostatin. Finally, co-immunoprecipitation studies showed that KChIP1 was associated with all three Kv4 α subunits. Together our results suggest that KChIP1 is selectively expressed in BLA interneurons where it may function to regulate the activity of A-type potassium channels. Hence, KChIP1 might be considered as a cell type-specific regulator of GABAergic inhibitory circuits in the BLA. PMID:20849929

  3. Metal artifact correction for x-ray computed tomography using kV and selective MV imaging

    SciTech Connect

    Wu, Meng; Keil, Andreas; Constantin, Dragos; Star-Lack, Josh; Zhu, Lei; Fahrig, Rebecca

    2014-12-15

    Purpose: The overall goal of this work is to improve the computed tomography (CT) image quality for patients with metal implants or fillings by completing the missing kilovoltage (kV) projection data with selectively acquired megavoltage (MV) data that do not suffer from photon starvation. When both of these imaging systems, which are available on current radiotherapy devices, are used, metal streak artifacts are avoided, and the soft-tissue contrast is restored, even for regions in which the kV data cannot contribute any information. Methods: Three image-reconstruction methods, including two filtered back-projection (FBP)-based analytic methods and one iterative method, for combining kV and MV projection data from the two on-board imaging systems of a radiotherapy device are presented in this work. The analytic reconstruction methods modify the MV data based on the information in the projection or image domains and then patch the data onto the kV projections for a FBP reconstruction. In the iterative reconstruction, the authors used dual-energy (DE) penalized weighted least-squares (PWLS) methods to simultaneously combine the kV/MV data and perform the reconstruction. Results: The authors compared kV/MV reconstructions to kV-only reconstructions using a dental phantom with fillings and a hip-implant numerical phantom. Simulation results indicated that dual-energy sinogram patch FBP and the modified dual-energy PWLS method can successfully suppress metal streak artifacts and restore information lost due to photon starvation in the kV projections. The root-mean-square errors of soft-tissue patterns obtained using combined kV/MV data are 10–15 Hounsfield units smaller than those of the kV-only images, and the structural similarity index measure also indicates a 5%–10% improvement in the image quality. The added dose from the MV scan is much less than the dose from the kV scan if a high efficiency MV detector is assumed. Conclusions: The authors have shown that it

  4. The design, construction, and operation of long-distance high-voltage electricity transmission technologies.

    SciTech Connect

    Molburg, J. C.; Kavicky, J. A.; Picel, K. C.

    2008-03-03

    This report focuses on transmission lines, which operate at voltages of 115 kV and higher. Currently, the highest voltage lines comprising the North American power grid are at 765 kV. The grid is the network of transmission lines that interconnect most large power plants on the North American continent. One transmission line at this high voltage was built near Chicago as part of the interconnection for three large nuclear power plants southwest of the city. Lines at this voltage also serve markets in New York and New England, also very high demand regions. The large power transfers along the West Coast are generally at 230 or 500 kV. Just as there are practical limits to centralization of power production, there are practical limits to increasing line voltage. As voltage increases, the height of the supporting towers, the size of the insulators, the distance between conductors on a tower, and even the width of the right-of-way (ROW) required increase. These design features safely isolate the electric power, which has an increasing tendency to arc to ground as the voltage (or electrical potential) increases. In addition, very high voltages (345 kV and above) are subject to corona losses. These losses are a result of ionization of the atmosphere, and can amount to several megawatts of wasted power. Furthermore, they are a local nuisance to radio transmission and can produce a noticeable hum. Centralized power production has advantages of economies of scale and special resource availability (for instance, hydro resources), but centralized power requires long-distance transfers of power both to reach customers and to provide interconnections for reliability. Long distances are most economically served at high voltages, which require large-scale equipment and impose a substantial footprint on the corridors through which power passes. The most visible components of the transmission system are the conductors that provide paths for the power and the towers that keep these

  5. Modulation of the transient outward current (Ito) in rat cardiac myocytes and human Kv4.3 channels by mefloquine.

    PubMed

    Perez-Cortes, E J; Islas, A A; Arevalo, J P; Mancilla, C; Monjaraz, E; Salinas-Stefanon, E M

    2015-10-15

    The antimalarial drug mefloquine, is known to be a potassium channel blocker, although its mechanism of action has not being elucidated and its effects on the transient outward current (Ito) and the molecular correlate, the Kv4.3 channel has not being studied. Here, we describe the mefloquine-induced inhibition of the rat ventricular Ito and of CHO cells co-transfected with human Kv4.3 and its accessory subunit hKChIP2C by whole-cell voltage-clamp. Mefloquine inhibited rat Ito and hKv4.3+KChIP2C currents in a concentration-dependent manner with a limited voltage dependence and similar potencies (IC50=8.9μM and 10.5μM for cardiac myocytes and Kv4.3 channels, respectively). In addition, mefloquine did not affect the activation of either current but significantly modified the hKv4.3 steady-state inactivation and recovery from inactivation. The effects of this drug was compared with that of 4-aminopyridine (4-AP), a well-known potassium channel blocker and its binding site does not seem to overlap with that of 4-AP.

  6. Cux1 Enables Interhemispheric Connections of Layer II/III Neurons by Regulating Kv1-Dependent Firing.

    PubMed

    Rodríguez-Tornos, Fernanda M; Briz, Carlos G; Weiss, Linnea A; Sebastián-Serrano, Alvaro; Ares, Saúl; Navarrete, Marta; Frangeul, Laura; Galazo, Maria; Jabaudon, Denis; Esteban, José A; Nieto, Marta

    2016-02-01

    Neuronal subtype-specific transcription factors (TFs) instruct key features of neuronal function and connectivity. Activity-dependent mechanisms also contribute to wiring and circuit assembly, but whether and how they relate to TF-directed neuronal differentiation is poorly investigated. Here we demonstrate that the TF Cux1 controls the formation of the layer II/III corpus callosum (CC) projections through the developmental transcriptional regulation of Kv1 voltage-dependent potassium channels and the resulting postnatal switch to a Kv1-dependent firing mode. Loss of Cux1 function led to a decrease in the expression of Kv1 transcripts, aberrant firing responses, and selective loss of CC contralateral innervation. Firing and innervation were rescued by re-expression of Kv1 or postnatal reactivation of Cux1. Knocking down Kv1 mimicked Cux1-mediated CC axonal loss. These findings reveal that activity-dependent processes are central bona fide components of neuronal TF-differentiation programs and establish the importance of intrinsic firing modes in circuit assembly within the neocortex.

  7. SUMO modification of cell surface Kv2.1 potassium channels regulates the activity of rat hippocampal neurons

    PubMed Central

    Plant, Leigh D.; Dowdell, Evan J.; Dementieva, Irina S.; Marks, Jeremy D.

    2011-01-01

    Voltage-gated Kv2.1 potassium channels are important in the brain for determining activity-dependent excitability. Small ubiquitin-like modifier proteins (SUMOs) regulate function through reversible, enzyme-mediated conjugation to target lysine(s). Here, sumoylation of Kv2.1 in hippocampal neurons is shown to regulate firing by shifting the half-maximal activation voltage (V1/2) of channels up to 35 mV. Native SUMO and Kv2.1 are shown to interact within and outside channel clusters at the neuronal surface. Studies of single, heterologously expressed Kv2.1 channels show that only K470 is sumoylated. The channels have four subunits, but no more than two non-adjacent subunits carry SUMO concurrently. SUMO on one site shifts V1/2 by 15 mV, whereas sumoylation of two sites produces a full response. Thus, the SUMO pathway regulates neuronal excitability via Kv2.1 in a direct and graded manner. PMID:21518833

  8. High voltage studies of inverted-geometry ceramic insulators for a 350 kV DC polarized electron gun

    DOE PAGES

    Hernandez-Garcia, C.; Poelker, M.; Hansknecht, J.

    2016-02-01

    Jefferson Lab is constructing a 350 kV direct current high voltage photoemission gun employing a compact inverted-geometry insulator. This photogun will produce polarized electron beams at an injector test facility intended for low energy nuclear physics experiments, and to assist the development of new technology for the Continuous Electron Beam Accelerator Facility. A photogun operating at 350kV bias voltage reduces the complexity of the injector design, by eliminating the need for a graded-beta radio frequency “capture” section employed to boost lower voltage beams to relativistic speed. However, reliable photogun operation at 350 kV necessitates solving serious high voltage problems relatedmore » to breakdown and field emission. This study focuses on developing effective methods to avoid breakdown at the interface between the insulator and the commercial high voltage cable that connects the photogun to the high voltage power supply. Three types of inverted insulators were tested, in combination with two electrode configurations. Our results indicate that tailoring the conductivity of the insulator material, and/or adding a cathode triple-junction screening electrode, effectively serves to increase the hold-off voltage from 300kV to more than 375kV. In conclusion, electrostatic field maps suggest these configurations serve to produce a more uniform potential gradient across the insulator.« less

  9. The inhibitory effect of propofol on Kv2.1 potassium channel in rat parietal cortical neurons.

    PubMed

    Zhang, Yan-Zhuo; Zhang, Rui; Zeng, Xian-Zhang; Song, Chun-Yu

    2016-03-11

    Excessive K(+) efflux via activated voltage-gated K(+) channels can deplete intracellular K(+) and lead to long-lasting membrane depolarization which will promote neuronal apoptosis during ischemia/hypoxia injury. The Kv2.1 potassium channel was the major component of delayed rectifier potassium current (Ik) in pyramidal neurons in cortex and hippocampus. The neuronal protective effect of propofol has been proved. Delayed rectifier potassium current (Ik) has been shown to have close relationship with neuronal damage. The study was designed to test the inhibitory effect of propofol on Kv2.1 potassium channel in rat parietal cortical neurons. Whole-cell patch clamp recordings and Western blot analysis were used to investigate the electrophysiological function and protein expression of Kv2.1 in rat parietal cortical neurons after propofol treatment. We found that propofol concentration-dependently inhibited Ik in pyramidal neurons. Propofol also caused a downward shift of the I-V curve of Ik at 30μM concentration. Propofol significantly inhibited the expression of Kv2.1 protein level at 30μM, 50μM, 100μM concentration. In conclusion, our data showed that propofol could inhibit Ik, probably via depressing the expression of Kv2.1 protein in rat cerebral parietal cortical neurons.

  10. Kv1.2 mediates heterosynaptic modulation of direct cortical synaptic inputs in CA3 pyramidal cells

    PubMed Central

    Hyun, Jung Ho; Eom, Kisang; Lee, Kyu-Hee; Bae, Jin Young; Bae, Yong Chul; Kim, Myoung-Hwan; Kim, Sooyun; Ho, Won-Kyung; Lee, Suk-Ho

    2015-01-01

    A short high frequency stimulation of mossy fibres (MFs) induces long-term potentiation (LTP) of direct cortical or perforant path (PP) synaptic inputs in hippocampal CA3 pyramidal cells (CA3-PCs). However, the cellular mechanism underlying this heterosynaptic modulation remains elusive. Previously, we reported that repetitive somatic firing at 10 Hz downregulates Kv1.2 in the CA3-PCs. Here, we show that MF inputs induce similar somatic firing and downregulation of Kv1.2 in the CA3-PCs. The effect of Kv1.2 downregulation was specific to PP synaptic inputs that arrive at distal apical dendrites. We found that the somatodendritic expression of Kv1.2 is polarized to distal apical dendrites. Compartmental simulations based on this finding suggested that passive normalization of synaptic inputs and polarized distributions of dendritic ionic channels may facilitate the activation of dendritic Na+ channels preferentially at distal apical dendrites. Indeed, partial block of dendritic Na+ channels using 10 nm tetrodotoxin brought back the enhanced PP-evoked excitatory postsynaptic potentials (PP-EPSPs) to the baseline level. These results indicate that activity-dependent downregulation of Kv1.2 in CA3-PCs mediates MF-induced heterosynaptic LTP of PP-EPSPs by facilitating activation of Na+ channels at distal apical dendrites. PMID:26047212

  11. Voltage-sensor conformation shapes the intra-membrane drug binding site that determines gambierol affinity in Kv channels.

    PubMed

    Kopljar, Ivan; Grottesi, Alessandro; de Block, Tessa; Rainier, Jon D; Tytgat, Jan; Labro, Alain J; Snyders, Dirk J

    2016-08-01

    Marine ladder-shaped polyether toxins are implicated in neurological symptoms of fish-borne food poisonings. The toxin gambierol, produced by the marine dinoflagellate Gambierdiscus toxicus, belongs to the group of ladder-shaped polyether toxins and inhibits Kv3.1 channels with nanomolar affinity through a mechanism of gating modification. Binding determinants for gambierol localize at the lipid-exposed interface of the pore forming S5 and S6 segments, suggesting that gambierol binds outside of the permeation pathway. To explore a possible involvement of the voltage-sensing domain (VSD), we made different chimeric channels between Kv3.1 and Kv2.1, exchanging distinct parts of the gating machinery. Our results showed that neither the electro-mechanical coupling nor the S1-S3a region of the VSD affect gambierol sensitivity. In contrast, the S3b-S4 part of the VSD (paddle motif) decreased gambierol sensitivity in Kv3.1 more than 100-fold. Structure determination by homology modeling indicated that the position of the S3b-S4 paddle and its primary structure defines the shape and∖or the accessibility of the binding site for gambierol, explaining the observed differences in gambierol affinity between the channel chimeras. Furthermore, these findings explain the observed difference in gambierol affinity for the closed and open channel configurations of Kv3.1, opening new possibilities for exploring the VSDs as selectivity determinants in drug design. PMID:26956727

  12. Specification of skeletal muscle differentiation by repressor element-1 silencing transcription factor (REST)-regulated Kv7.4 potassium channels

    PubMed Central

    Iannotti, Fabio Arturo; Barrese, Vincenzo; Formisano, Luigi; Miceli, Francesco; Taglialatela, Maurizio

    2013-01-01

    Changes in the expression of potassium (K+) channels is a pivotal event during skeletal muscle differentiation. In mouse C2C12 cells, similarly to human skeletal muscle cells, myotube formation increased the expression of Kv7.1, Kv7.3, and Kv7.4, the last showing the highest degree of regulation. In C2C12 cells, Kv7.4 silencing by RNA interference reduced the expression levels of differentiation markers (myogenin, myosin heavy chain, troponinT-1, and Pax3) and impaired myotube formation and multinucleation. In Kv7.4-silenced cells, the differentiation-promoting effect of the Kv7 activator N-(2-amino-4-(4-fluorobenzylamino)-phenyl)-carbamic acid ethyl ester (retigabine) was abrogated. Expression levels for the repressor element-1 silencing transcription factor (REST) declined during myotube formation. Transcript levels for Kv7.4, as well as for myogenin, troponinT-1, and Pax3, were reduced by REST overexpression and enhanced upon REST suppression by RNA interference. Four regions containing potential REST-binding sites in the 5′ untranslated region and in the first intron of the Kv7.4 gene were identified by bioinformatic analysis. Chromatin immunoprecipitation assays showed that REST binds to these regions, exhibiting a higher efficiency in myoblasts than in myotubes. These data suggest that Kv7.4 plays a permissive role in skeletal muscle differentiation and highlight REST as a crucial transcriptional regulator for this K+ channel subunit. PMID:23242999

  13. Novel Roles for Kv7 Channels in Shaping Histamine-Induced Contractions and Bradykinin-Dependent Relaxations in Pig Coronary Arteries.

    PubMed

    Chen, Xingjuan; Li, Wennan; Hiett, S Christopher; Obukhov, Alexander G

    2016-01-01

    Voltage-gated Kv7 channels are inhibited by agonists of Gq-protein-coupled receptors, such as histamine. Recent works have provided evidence that inhibition of vascular Kv7 channels may trigger vessel contractions. In this study, we investigated how Kv7 activity modulates the histamine-induced contractions in "healthy" and metabolic syndrome (MetS) pig right coronary arteries (CAs). We performed isometric tension and immunohistochemical studies with domestic, lean Ossabaw, and MetS Ossabaw pig CAs. We found that neither the Kv7.2/Kv7.4/Kv7.5 activator ML213 nor the general Kv7 inhibitor XE991 altered the tension of CA rings under preload, indicating that vascular Kv7 channels are likely inactive in the preloaded rings. Conversely, ML213 potently dilated histamine-pre-contracted CAs, suggesting that Kv7 channels are activated during histamine applications and yet partially inhibited by histamine. Immunohistochemistry analysis revealed strong Kv7.4 immunostaining in the medial and intimal layers of the CA wall, whereas Kv7.5 immunostaining intensity was strong in the intimal but weak in the medial layers. The medial Kv7 immunostaining was significantly weaker in MetS Ossabaw CAs as compared to lean Ossabaw or domestic CAs. Consistently, histamine-pre-contracted MetS Ossabaw CAs exhibited attenuated ML213-dependent dilations. In domestic pig CAs, where medial Kv7 immunostaining intensity was stronger, histamine-induced contractions spontaneously decayed to ~31% of the peak amplitude within 4 minutes. Oppositely, in Ossabaw CAs, where Kv7 immunostaining intensity was weaker, the histamine-induced contractions were more sustained. XE991 pretreatment significantly slowed the decay rate of histamine-induced contractions in domestic CAs, supporting the hypothesis that increased Kv7 activity correlates with a faster rate of histamine-induced contraction decay. Alternatively, XE991 significantly decreased the amplitude of bradykinin-dependent dilations in pre-contracted CAs

  14. A recurrent KCNQ2 pore mutation causing early onset epileptic encephalopathy has a moderate effect on M current but alters subcellular localization of Kv7 channels.

    PubMed

    Abidi, Affef; Devaux, Jérôme J; Molinari, Florence; Alcaraz, Gisèle; Michon, François-Xavier; Sutera-Sardo, Julie; Becq, Hélène; Lacoste, Caroline; Altuzarra, Cécilia; Afenjar, Alexandra; Mignot, Cyril; Doummar, Diane; Isidor, Bertrand; Guyen, Sylvie N; Colin, Estelle; De La Vaissière, Sabine; Haye, Damien; Trauffler, Adeline; Badens, Catherine; Prieur, Fabienne; Lesca, Gaetan; Villard, Laurent; Milh, Mathieu; Aniksztejn, Laurent

    2015-08-01

    Mutations in the KCNQ2 gene encoding the voltage-dependent potassium M channel Kv7.2 subunit cause either benign epilepsy or early onset epileptic encephalopathy (EOEE). It has been proposed that the disease severity rests on the inhibitory impact of mutations on M current density. Here, we have analyzed the phenotype of 7 patients carrying the p.A294V mutation located on the S6 segment of the Kv7.2 pore domain (Kv7.2(A294V)). We investigated the functional and subcellular consequences of this mutation and compared it to another mutation (Kv7.2(A294G)) associated with a benign epilepsy and affecting the same residue. We report that all the patients carrying the p.A294V mutation presented the clinical and EEG characteristics of EOEE. In CHO cells, the total expression of Kv7.2(A294V) alone, assessed by western blotting, was only 20% compared to wild-type. No measurable current was recorded in CHO cells expressing Kv7.2(A294V) channel alone. Although the total Kv7.2(A294V) expression was rescued to wild-type levels in cells co-expressing the Kv7.3 subunit, the global current density was still reduced by 83% compared to wild-type heteromeric channel. In a configuration mimicking the patients' heterozygous genotype i.e., Kv7.2(A294V)/Kv7.2/Kv7.3, the global current density was reduced by 30%. In contrast to Kv7.2(A294V), the current density of homomeric Kv7.2(A294G) was not significantly changed compared to wild-type Kv7.2. However, the current density of Kv7.2(A294G)/Kv7.2/Kv7.3 and Kv7.2(A294G)/Kv7.3 channels were reduced by 30% and 50% respectively, compared to wild-type Kv7.2/Kv7.3. In neurons, the p.A294V mutation induced a mislocalization of heteromeric mutant channels to the somato-dendritic compartment, while the p.A294G mutation did not affect the localization of the heteromeric channels to the axon initial segment. We conclude that this position is a hotspot of mutation that can give rise to a severe or a benign epilepsy. The p.A294V mutation does not exert a

  15. Supplement Analysis for the Transmission System Vegetation Management Program FEIS (DOE/EIS-0285/SA-60) - Rocky Reach - Maple Valley No. 1

    SciTech Connect

    Martin, Mark A.

    2002-04-15

    Vegetation Management along the Rocky Reach – Maple Valley No. 1 Transmission Line ROW from structure 110/1 to the Maple Valley Substation. The transmission line is a 500 kV line. BPA proposes to clear targeted vegetation along access roads and around tower structures that may impede the operation and maintenance of the subject transmission line. BPA plans to conduct vegetation management along existing access road and around structure landings for the purpose of maintaining access to structures site. All work will be in accordance with the National Electrical Safety Code and BPA standards.

  16. Passenger car transmissions

    SciTech Connect

    Not Available

    1990-01-01

    This book is organized under the following headings. The Mercedes-Benz 5-speed automatic transmission targets and comparison of concepts. 1991 model year Chrysler mini-van all wheel drive vehicle. Mesh stiffness and transmission error of spur and helical gears. High precision cutting tool system for the manufacture of world class powertrain components.

  17. Transmission Line Security Monitor

    SciTech Connect

    2011-01-01

    The Transmission Line Security Monitor is a multi-sensor monitor that mounts directly on high-voltage transmission lines to detect, characterize and communicate terrorist activity, human tampering and threatening conditions around support towers. For more information about INL's critical infrastructure protection research, visit http://www.facebook.com/idahonationallaboratory.

  18. Transmission Line Security Monitor

    ScienceCinema

    None

    2016-07-12

    The Transmission Line Security Monitor is a multi-sensor monitor that mounts directly on high-voltage transmission lines to detect, characterize and communicate terrorist activity, human tampering and threatening conditions around support towers. For more information about INL's critical infrastructure protection research, visit http://www.facebook.com/idahonationallaboratory.

  19. Automatic transmission control method

    SciTech Connect

    Hasegawa, H.; Ishiguro, T.

    1989-07-04

    This patent describes a method of controlling an automatic transmission of an automotive vehicle. The transmission has a gear train which includes a brake for establishing a first lowest speed of the transmission, the brake acting directly on a ring gear which meshes with a pinion, the pinion meshing with a sun gear in a planetary gear train, the ring gear connected with an output member, the sun gear being engageable and disengageable with an input member of the transmission by means of a clutch. The method comprises the steps of: detecting that a shift position of the automatic transmission has been shifted to a neutral range; thereafter introducing hydraulic pressure to the brake if present vehicle velocity is below a predetermined value, whereby the brake is engaged to establish the first lowest speed; and exhausting hydraulic pressure from the brake if present vehicle velocity is higher than a predetermined value, whereby the brake is disengaged.

  20. Trailing (L5) Neptune Trojans: 2004 KV18 and 2008 LC18

    NASA Astrophysics Data System (ADS)

    Guan, Pu; Zhou, Li-Yong; Li, Jian

    2012-11-01

    The population of Neptune Trojans is believed to be bigger than that of Jupiter Trojans and that of asteroids in the main belt, although only eight members of this distant asteroid swarm have been observed up to now. Six leading Neptune Trojans around the Lagrange point L4 discovered earlier have been studied in detail, but two trailing ones found recently around the L5 point, 2004 KV18 and 2008 LC18, have not yet been investigated. We report our investigations on the dynamical behaviors of these two new Neptune Trojans. Our calculations show that the asteroid 2004 KV18 is a temporary Neptune Trojan. Most probably, it was captured into the trailing Trojan cloud no earlier than 2.03 × 105 yr ago, and it will not maintain this position later than 1.65 × 105 yr in the future. Based on the statistics from our orbital simulations, we argue that this object is more like a scattered Kuiper belt object. By contrast, the orbit of 2008 LC18 is much more stable. Among the clone orbits spreading within the orbital uncertainties, a considerable portion of clones may survive on the L5 tadpole orbits for 4 Gyr. The strong dependence of the stability on the semimajor axis and resonant angle suggests that further observations are badly required to constrain the orbit in the stable region. We also discuss the implications of the existence and dynamics of these two trailing Trojans over the history of the solar system.

  1. A Model of Voltage Gating Developed Using the KvAP Channel Crystal Structure

    PubMed Central

    Shrivastava, Indira H.; Durell, Stewart R.; Guy, H. Robert

    2004-01-01

    Having inspected the crystal structure of the complete KvAP channel protein, we suspect that the voltage-sensing domain is too distorted to provide reliable information about its native tertiary structure or its interactions with the central pore-forming domain. On the other hand, a second crystal structure of the isolated voltage-sensing domain may well correspond to a native open conformation. We also observe that the paddle model of gating developed from these two structures is inconsistent with many experimental results, and suspect it to be energetically unrealistic. Here we show that the isolated voltage-sensing domain crystal structure can be docked onto the pore domain portion of the full-length KvAP crystal structure in an energetically favorable way to create a model of the open conformation. Using this as a starting point, we have developed rather conventional models of resting and transition conformations based on the helical screw mechanism for the transition from the open to the resting conformation. Our models are consistent with both theoretical considerations and experimental results. PMID:15454428

  2. Evolutionary conservation of Kv3.1 in the barn owl Tyto alba.

    PubMed

    Kullmann, Lars; Schlüter, Tina; Wagner, Hermann; Nothwang, Hans Gerd

    2013-01-01

    For prey capture in the dark, the barn owl Tyto alba has evolved into an auditory specialist with an exquisite capability of sound localization. Adaptations include asymmetrical ears, enlarged auditory processing centers, the utilization of minute interaural time differences, and phase locking along the entire hearing range up to 10 kHz. Adaptations on the molecular level have not yet been investigated. Here, we tested the hypothesis that divergence in the amino acid sequence of the voltage-gated K(+) channel Kv3.1 contributes to the accuracy and high firing rates of auditory neurons in the barn owl. We therefore cloned both splice variants of Kcnc1, the gene encoding Kv3.1. Both splice variants, Kcnc1a and Kcnc1b, encode amino acids identical to those of the chicken, an auditory generalist. Expression analyses confirmed neural-restricted expression of the channel. In summary, our data reveal strong evolutionary conservation of Kcnc1 in the barn owl and point to other genes involved in auditory specializations of this animal. The data also demonstrate the feasibility to address neuroethological questions in organisms with no reference genome by molecular approaches. This will open new avenues for neuroethologists working in these organisms. PMID:23615168

  3. A compact 45 kV curve tracer with picoampere current measurement capability

    NASA Astrophysics Data System (ADS)

    Sullivan, W. W.; Mauch, D.; Bullick, A.; Hettler, C.; Neuber, A.; Dickens, J.

    2013-03-01

    This paper discusses a compact high voltage curve tracer for high voltage semiconductor device characterization. The system sources up to 3 mA at up to 45 kV in dc conditions. It measures from 328 V to 60 kV with 15 V resolution and from 9.4 pA to 4 mA with 100 fA minimum resolution. Control software for the system is written in Microsoft Visual C# and features real-time measurement control and IV plotting, arc-protection and detection, an electrically isolated universal serial bus interface, and easy data exporting capabilities. The system has survived numerous catastrophic high voltage device-under-test arcing failures with no loss of measurement capability or system damage. Overall sweep times are typically under 2 min, and the curve tracer system was used to characterize the blocking performance of high voltage ceramic capacitors, high voltage silicon carbide photoconductive semiconductor switches, and high voltage coaxial cable.

  4. An unconventional calmodulin-anchoring site within the AB module of Kv7.2 channels.

    PubMed

    Gomis-Perez, Carolina; Alaimo, Alessandro; Fernandez-Orth, Juncal; Alberdi, Araitz; Aivar-Mateo, Paloma; Bernardo-Seisdedos, Ganeko; Malo, Covadonga; Areso, Pilar; Felipe, Antonio; Villarroel, Alvaro

    2015-08-15

    Calmodulin (CaM) binding to the AB module is crucial for multiple mechanisms governing the function of Kv7.2 (also known as KCNQ2) K(+) channel subunits, which mediate one of the main components of the non-inactivating K(+) M-current, a key controller of neuronal excitability. Structural analysis indicates that the CaM N-lobe engages with helix B, whereas the C-lobe anchors to the IQ site within helix A. Here, we report the identification of a new site between helices A and B that assists in CaM binding whose sequence is reminiscent of the TW helix within the CaM C-lobe anchoring site of SK2 K(+) channels (also known as KCNN2). Mutations that disrupt CaM binding within the TW site, helix B or helix A yield functional channels, whereas no function is observed when the TW site and helix A, or the TW site and helix B are mutated simultaneously. Our data indicate that the TW site is dispensable for function, contributes to the stabilization of the CaM-Kv7.2 complex and becomes essential when docking to either helix A or when helix B is perturbed.

  5. Evolutionary conservation of Kv3.1 in the barn owl Tyto alba.

    PubMed

    Kullmann, Lars; Schlüter, Tina; Wagner, Hermann; Nothwang, Hans Gerd

    2013-01-01

    For prey capture in the dark, the barn owl Tyto alba has evolved into an auditory specialist with an exquisite capability of sound localization. Adaptations include asymmetrical ears, enlarged auditory processing centers, the utilization of minute interaural time differences, and phase locking along the entire hearing range up to 10 kHz. Adaptations on the molecular level have not yet been investigated. Here, we tested the hypothesis that divergence in the amino acid sequence of the voltage-gated K(+) channel Kv3.1 contributes to the accuracy and high firing rates of auditory neurons in the barn owl. We therefore cloned both splice variants of Kcnc1, the gene encoding Kv3.1. Both splice variants, Kcnc1a and Kcnc1b, encode amino acids identical to those of the chicken, an auditory generalist. Expression analyses confirmed neural-restricted expression of the channel. In summary, our data reveal strong evolutionary conservation of Kcnc1 in the barn owl and point to other genes involved in auditory specializations of this animal. The data also demonstrate the feasibility to address neuroethological questions in organisms with no reference genome by molecular approaches. This will open new avenues for neuroethologists working in these organisms.

  6. Fast internal marker tracking algorithm for onboard MV and kV imaging systems.

    PubMed

    Mao, W; Wiersma, R D; Xing, L

    2008-05-01

    Intrafraction organ motion can limit the advantage of highly conformal dose techniques such as intensity modulated radiation therapy (IMRT) due to target position uncertainty. To ensure high accuracy in beam targeting, real-time knowledge of the target location is highly desired throughout the beam delivery process. This knowledge can be gained through imaging of internally implanted radio-opaque markers with fluoroscopic or electronic portal imaging devices (EPID). In the case of MV based images, marker detection can be problematic due to the significantly lower contrast between different materials in comparison to their kV-based counterparts. This work presents a fully automated algorithm capable of detecting implanted metallic markers in both kV and MV images with high consistency. Using prior CT information, the algorithm predefines the volumetric search space without manual region-of-interest (ROI) selection by the user. Depending on the template selected, both spherical and cylindrical markers can be detected. Multiple markers can be simultaneously tracked without indexing confusion. Phantom studies show detection success rates of 100% for both kV and MV image data. In addition, application of the algorithm to real patient image data results in successful detection of all implanted markers for MV images. Near real-time operational speeds of approximately 10 frames/sec for the detection of five markers in a 1024 x 768 image are accomplished using an ordinary PC workstation.

  7. Pulsed power supply for streamer corona electrofilter with 100 KV pseudospark switch

    SciTech Connect

    Bochkov, V.D.; Gnedin, I.N.; Djagiley, V.M.

    1996-12-31

    The pulsed-plasma-based reactor is currently created for the biggest in Moscow region thermal Kashira Power Plant. The reactor is intended to increase a precipitation of fly ash, SO{sub 2} and NO{sub x} from flue gas. The principal parameters of the electrostatic precipitator and pulse power supply for streamer corona discharge are as follows: gas flow rate - 300000 Nm{sup 3}/h gas velocity - 2 m/s, average power - 300 kW, pulse repetition rate - up to 2 kHz. The power supply has a module design with the single module power of about 25-50 kW, pulse voltage up to 120 kV, pulse energy of 30 J, pulse length of 500 ns. The pseudospark switch with hold-off voltage up to 100 kV is used in the module. It is supposed that the switch should offer a possibility to transfer a total charge of about 10{sup 7} C.

  8. Optimizing 50kV hydrogen diagnostic neutral beam performance for active spectroscopy in MST

    NASA Astrophysics Data System (ADS)

    Feng, X.; Boguski, J.; Craig, D.; den Hartog, D. J.; Munaretto, S.; Nornberg, M. D.; Olivia, S.

    2015-11-01

    The 50 kV hydrogen diagnostic neutral beam on MST provides local measurements of impurity ion emission through charge exchange recombination spectroscopy (CHERS) and of core-localized magnetic field through the motional Stark effect (MSE). The beam, which was designed to provide 5A of neutral current at 50 kV to meet these needs, is currently on a test stand to accommodate diagnosis, in order to increase the reliability of beam formation, sustain a steady current of 5 amps for 20ms, and optimize the primary energy fraction. The reliability of arc formation was increased from 40% to 80% success rate with increase of cathode gas pressure from 150kPa to 200kPa, and the stability of the arc current is improved with a decrease of the insulation magnetic field. A calorimeter with 5 thermocouples is installed to measure the horizontal and vertical beam profiles as well as beam divergence. Beam energy components are quantified through Doppler-shift spectroscopy. Preliminary simulation results of the beam using the ALCBEAM code as well as a description of how changes to the beam performance can affect CHERS and MSE measurements are presented. This work is supported by the U.S. DOE.

  9. Microdosimetric characteristics of 50 kV X rays at different depths for breast intraoperative radiotherapy.

    PubMed

    Wuu, Cheng-Shie; Sheu, Ren-Dih; Chen, Jing

    2015-09-01

    An intraoperative radiation therapy (IORT) device with 50 kV X rays was designed to deliver a single dose to the tumour bed after local excision of breast cancer. The quality of a radiation can be determined by the microscopic distribution of energy transfers along and across the charged particle tracks. The lineal energy, y, serves as an accurate measure of local energy concentration. The dose mean lineal energy, yD, is an indicator of radiation quality. For low linear energy transfer radiation, the ratio of its dose mean lineal energy to that of (60)Co gamma rays can serve as a good indicator of the relative biological effectiveness (RBE) at low doses. In this study, microdosimetric simulations are performed for soft tissue irradiated by 50 kV X rays generated from the IORT device, with a 4-cm breast applicator attached. All energy transfers are recorded with the location coordinates in the tissue. Microdosimetric single events in a sphere of 1 µm in diameter are scored as a function of radial distances from the applicator surface. Single-event spectra are then constructed. From those single-event spectra, dose mean lineal energy is calculated. Compared with dose mean lineal energy of (60)Co gamma rays, the estimated RBEs at low doses are given for the X rays at different depths in the tissue. The RBEs at clinically relevant doses, as a function of depth, are also presented.

  10. Systematic offset of kV and MV localization systems as a function of gantry angle.

    PubMed

    Mullins, John P; Herman, Michael G

    2010-11-09

    Mechanical flex of the gantry and mounted imaging panels leads to systematic offsets in localization image isocenter as a function of gantry angle for linear accelerator-mounted image guidance systems. Subsequently, object positions obtained from localization radiographs may be offset, resulting in greater target positioning uncertainty. While current QA procedures measure kV/MV image agreement, these measurements do not provide insight to apparent isocenter position for either single imaging system as a function of gantry rotation. This study measures offset as a function of gantry angle in kV and MV imaging systems on four treatment machines to investigate the magnitude of systematic offsets and their reproducibility between systems and machines, as well as over time. It is shown that each machine and energy has a reproducible pattern of offset as a function of gantry angle that is independent of kV/MV agreement, and it varies by machine. kV and MV offset ranges are on the order of 1.5 mm in the R/L and A/P directions, and 0.5 mm in the S/I direction. Variability of kV-MV agreement is on the order of 0.7 mm. At certain angles, combinations of localization images could show a compounded offset of over 2 mm, exceeding the desired certainty threshold. Since these trends are persistent over time for each machine, online correction for image offsets as a function of gantry angle could improve the margin of positioning uncertainty.

  11. Convergent Ca2+ and Zn2+ signaling regulates apoptotic Kv2.1 K+ currents

    PubMed Central

    McCord, Meghan C.; Aizenman, Elias

    2013-01-01

    A simultaneous increase in cytosolic Zn2+ and Ca2+ accompanies the initiation of neuronal cell death signaling cascades. However, the molecular convergence points of cellular processes activated by these cations are poorly understood. Here, we show that Ca2+-dependent activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) is required for a cell death-enabling process previously shown to also depend on Zn2+. We have reported that oxidant-induced intraneuronal Zn2+ liberation triggers a syntaxin-dependent incorporation of Kv2.1 voltage-gated potassium channels into the plasma membrane. This channel insertion can be detected as a marked enhancement of delayed rectifier K+ currents in voltage clamp measurements observed at least 3 h following a short exposure to an apoptogenic stimulus. This current increase is the process responsible for the cytoplasmic loss of K+ that enables protease and nuclease activation during apoptosis. In the present study, we demonstrate that an oxidative stimulus also promotes intracellular Ca2+ release and activation of CaMKII, which, in turn, modulates the ability of syntaxin to interact with Kv2.1. Pharmacological or molecular inhibition of CaMKII prevents the K+ current enhancement observed following oxidative injury and, importantly, significantly increases neuronal viability. These findings reveal a previously unrecognized cooperative convergence of Ca2+- and Zn2+-mediated injurious signaling pathways, providing a potentially unique target for therapeutic intervention in neurodegenerative conditions associated with oxidative stress. PMID:23918396

  12. Engineering of beam direct conversion for a 120-kV, 1-MW ion beam

    NASA Technical Reports Server (NTRS)

    Barr, W. L.; Doggett, J. N.; Hamilton, G. W.; Kinney, J. D.; Moir, R. W.

    1977-01-01

    Practical systems for beam direct conversion are required to recover the energy from ion beams at high efficiency and at very high beam power densities in the environment of a high-power neutral-injection system. Such an experiment is now in progress using a 120-kV beam with a maximum total current of 20 A. After neutralization, the H(+) component to be recovered will have a power of approximately 1 MW. A system testing these concepts has been designed and tested at 15 kV, 2 kW in preparation for the full-power tests. The engineering problems involved in the full-power tests affect electron suppression, gas pumping, voltage holding, diagnostics, and measurement conditions. Planning for future experiments at higher power includes the use of cryopumping and electron suppression by a magnetic field rather than by an electrostatic field. Beam direct conversion for large fusion experiments and reactors will save millions of dollars in the cost of power supplies and electricity and will dispose of the charged beam under conditions that may not be possible by other techniques.

  13. Fast internal marker tracking algorithm for onboard MV and kV imaging systems

    PubMed Central

    Mao, W.; Wiersma, R. D.; Xing, L.

    2008-01-01

    Intrafraction organ motion can limit the advantage of highly conformal dose techniques such as intensity modulated radiation therapy (IMRT) due to target position uncertainty. To ensure high accuracy in beam targeting, real-time knowledge of the target location is highly desired throughout the beam delivery process. This knowledge can be gained through imaging of internally implanted radio-opaque markers with fluoroscopic or electronic portal imaging devices (EPID). In the case of MV based images, marker detection can be problematic due to the significantly lower contrast between different materials in comparison to their kV-based counterparts. This work presents a fully automated algorithm capable of detecting implanted metallic markers in both kV and MV images with high consistency. Using prior CT information, the algorithm predefines the volumetric search space without manual region-of-interest (ROI) selection by the user. Depending on the template selected, both spherical and cylindrical markers can be detected. Multiple markers can be simultaneously tracked without indexing confusion. Phantom studies show detection success rates of 100% for both kV and MV image data. In addition, application of the algorithm to real patient image data results in successful detection of all implanted markers for MV images. Near real-time operational speeds of ∼10 frames∕sec for the detection of five markers in a 1024×768 image are accomplished using an ordinary PC workstation. PMID:18561670

  14. Development of resist process for 5-KV multi-beam technology

    NASA Astrophysics Data System (ADS)

    Icard, B.; Rio, D.; Veltman, P.; Kampherbeek, B.; Constancias, C.; Pain, L.

    2009-03-01

    E-beam Maskless activities raised a lot of interest in the past years from semiconductor companies strongly concerned by the constant cost increase of masked-based lithography (1). Beginning of 2008, the European Commission started an integrated program called "MAGIC", Maskless lithography for IC manufacturing, which pushes the development and the insertion of the European multi-beam technology (2) in the semiconductor industry. This project supports also to develop the infrastructure for the use of this technology, including resist processes, data processing and proximity corrections. Within MAGIC, MAPPER develops its low energy (5keV) massively parallel concept (3). Compared to a standard single E-Beam machine working classically at 50kV, this low accelerating voltage requires the use of thin resist film to deal with the lower penetration depth of the electrons. This paper presents the resist development status, including Chemically Amplified Resist and non-CAR platforms. Comparisons of the performances of these resist platforms in terms of resolution, sensitivity, roughness and stability are detailed, including their potential integration into CMOS technological flow. Finally, a first review of the state of the art of resist performance for patterning at 5kV will be performed. Based on the level of achievements presented in this paper, a discussion is also engaged about the needs of resist developments to fulfill industry targets in 2011.

  15. Optically isolated, 2 kHz repetition rate, 4 kV solid-state pulse trigger generator.

    PubMed

    Barnett, D H; Parson, J M; Lynn, C F; Kelly, P M; Taylor, M; Calico, S; Scott, M C; Dickens, J C; Neuber, A A; Mankowski, J J

    2015-03-01

    This paper presents the design and operation characteristics of a solid-state high voltage pulse generator. Its primary utilization is aimed at triggering a gaseous spark gap with high repeatability. Specifically, the trigger generator is designed to achieve a risetime on the order of 0.1 kV/ns to trigger the first stage, trigatron spark gap of a 10-stage, 500 kV Marx generator. The major design components are comprised of a 60 W constant current DC-DC converter for high voltage charging, a single 4 kV thyristor, a step-up pulse transformer, and magnetic switch for pulse steepening. A risetime of <30 ns and pulse magnitude of 4 kV is achieved matching the simulated performance of the design.

  16. Optically isolated, 2 kHz repetition rate, 4 kV solid-state pulse trigger generator

    NASA Astrophysics Data System (ADS)

    Barnett, D. H.; Parson, J. M.; Lynn, C. F.; Kelly, P. M.; Taylor, M.; Calico, S.; Scott, M. C.; Dickens, J. C.; Neuber, A. A.; Mankowski, J. J.

    2015-03-01

    This paper presents the design and operation characteristics of a solid-state high voltage pulse generator. Its primary utilization is aimed at triggering a gaseous spark gap with high repeatability. Specifically, the trigger generator is designed to achieve a risetime on the order of 0.1 kV/ns to trigger the first stage, trigatron spark gap of a 10-stage, 500 kV Marx generator. The major design components are comprised of a 60 W constant current DC-DC converter for high voltage charging, a single 4 kV thyristor, a step-up pulse transformer, and magnetic switch for pulse steepening. A risetime of <30 ns and pulse magnitude of 4 kV is achieved matching the simulated performance of the design.

  17. Tyrosine Residues from the S4-S5 Linker of Kv11.1 Channels Are Critical for Slow Deactivation.

    PubMed

    Ng, Chai-Ann; Gravel, Andrée E; Perry, Matthew D; Arnold, Alexandre A; Marcotte, Isabelle; Vandenberg, Jamie I

    2016-08-12

    Slow deactivation of Kv11.1 channels is critical for its function in the heart. The S4-S5 linker, which joins the voltage sensor and pore domains, plays a critical role in this slow deactivation gating. Here, we use NMR spectroscopy to identify the membrane-bound surface of the S4S5 linker, and we show that two highly conserved tyrosine residues within the KCNH subfamily of channels are membrane-associated. Site-directed mutagenesis and electrophysiological analysis indicates that Tyr-542 interacts with both the pore domain and voltage sensor residues to stabilize activated conformations of the channel, whereas Tyr-545 contributes to the slow kinetics of deactivation by primarily stabilizing the transition state between the activated and closed states. Thus, the two tyrosine residues in the Kv11.1 S4S5 linker play critical but distinct roles in the slow deactivation phenotype, which is a hallmark of Kv11.1 channels.

  18. Long-term stability and mechanical characteristics of kV digital imaging system for proton radiotherapy

    SciTech Connect

    Zhu, Mingyao Botticello, Thomas; Lu, Hsiao-Ming; Winey, Brian

    2014-04-15

    Purpose: To quantitatively evaluate the long-term image panel positioning stability and gantry angle dependence for gantry-mounted kV imaging systems. Methods: For patient setup digital imaging systems in isocentric rotating proton beam delivery facilities, physical crosshairs are commonly inserted into the snout to define the kV x-ray beam isocenter. Utilizing an automatic detection algorithm, the authors analyzed the crosshair center positions in 2744 patient setup kV images acquired with the four imagers in two treatment rooms from January 2012 to January 2013. The crosshair position was used as a surrogate for imaging panel position, and its long-term stability at the four cardinal angles and the panel flex dependency on gantry angle was investigated. Results: The standard deviation of the panel position distributions was within 0.32 mm (with the range of variation less than ± 1.4 mm) in both the X-Z plane and Y direction. The mean panel inplane rotations were not more than 0.51° for the four panels at the cardinal angles, with standard deviations ≤0.26°. The panel position variations with gantry rotation due to gravity (flex) were within ±4 mm, and were panel-specific. Conclusions: The authors demonstrated that the kV image panel positions in our proton treatment system were highly reproducible at the cardinal angles over 13 months and also that the panel positions can be correlated to gantry angles. This result indicates that the kV image panel positions are stable over time; the amount of panel sag is predictable during gantry rotation and the physical crosshair for kV imaging may eventually be removed, with the imaging beam isocenter position routinely verified by adequate quality assurance procedures and measurements.

  19. Granzyme B-Induced Neurotoxicity Is Mediated via Activation of PAR-1 Receptor and Kv1.3 Channel

    PubMed Central

    Wang, Tongguang; Lee, Myoung-Hwa; Choi, Elliot; Pardo-Villamizar, Carlos A.; Lee, Sung Bin; Yang, In Hong; Calabresi, Peter A.; Nath, Avindra

    2012-01-01

    Increasing evidence supports a critical role of T cells in neurodegeneration associated with acute and subacute brain inflammatory disorders. Granzyme B (GrB), released by activated T cells, is a cytotoxic proteinase which may induce perforin-independent neurotoxicity. Here, we studied the mechanism of perforin-independent GrB toxicity by treating primary cultured human neuronal cells with recombinant GrB. GrBactivated the protease-activated receptor (PAR)-1 receptor on the neuronal cell surface leading to decreased intracellular cyclic AMP levels. This was followed by increased expression and translocation of the voltage gated potassium channel, Kv1.3 to the neuronal cell membrane. Similar expression of Kv1.3 was also seen in neurons of the cerebral cortex adjacent to active inflammatory lesions in patients with multiple sclerosis. Kv1.3 expression was followed by activation of Notch-1 resulting in neurotoxicity. Blocking PAR-1, Kv1.3 or Notch-1 activation using specific pharmacological inhibitors or siRNAs prevented GrB-induced neurotoxicity. Furthermore, clofazimine protected against GrB-induced neurotoxicity in rat hippocampus, in vivo. These observations indicate that GrB released from T cells induced neurotoxicity by interacting with the membrane bound Gi-coupled PAR-1 receptor and subsequently activated Kv1.3 and Notch-1. These pathways provide novel targets to treat T cell-mediated neuroinflammatory disorders. Kv1.3 is of particular interest since it is expressed on the cell surface, only under pathological circumstances, and early in the cascade of events making it an attractive therapeutic target. PMID:22952817

  20. Hyperexcitability and reduced low threshold potassium currents in auditory neurons of mice lacking the channel subunit Kv1.1

    PubMed Central

    Brew, Helen M; Hallows, Janice L; Tempel, Bruce L

    2003-01-01

    A low voltage-activated potassium current, IKL, is found in auditory neuron types that have low excitability and precisely preserve the temporal pattern of activity present in their presynaptic inputs. The gene Kcnal codes for Kv1.1 potassium channel subunits, which combine in expression systems to produce channel tetramers with properties similar to those of IKL, including sensitivity to dendrotoxin (DTX). Kv1.1 is strongly expressed in neurons with IKL, including auditory neurons of the medial nucleus of the trapezoid body (MNTB). We therefore decided to investigate how the absence of Kv1.1 affected channel properties and function in MNTB neurons from mice lacking Kcnal. We used the whole cell version of the patch clamp technique to record from MNTB neurons in brainstem slices from Kcnal-null (−/−) mice and their wild-type (+/+) and heterozygous (+/−) littermates. There was an IKL in voltage-clamped −/− MNTB neurons, but it was about half the amplitude of the IKL in +/+ neurons, with otherwise similar properties. Consistent with this, −/− MNTB neurons were more excitable than their +/+ counterparts; they fired more than twice as many action potentials (APs) during current steps, and the threshold current amplitude required to generate an AP was roughly halved. +/− MNTB neurons had excitability and IKL amplitudes identical to the +/+ neurons. The IKL remaining in −/− neurons was blocked by DTX, suggesting the underlying channels contained subunits Kv1.2 and/or Kv1.6 (also DTX-sensitive). DTX increased excitability further in the already hyperexcitable −/− MNTB neurons, suggesting that −/−IKL limited excitability despite its reduced amplitude in the absence of Kv1.1 subunits. PMID:12611922

  1. Curcumin serves as a human kv1.3 blocker to inhibit effector memory T lymphocyte activities.

    PubMed

    Lian, Yi-Tian; Yang, Xiao-Fang; Wang, Zhao-Hui; Yang, Yong; Yang, Ying; Shu, Yan-Wen; Cheng, Long-Xian; Liu, Kun

    2013-09-01

    Curcumin, the principal active component of turmeric, has long been used to treat various diseases in India and China. Recent studies show that curcumin can serve as a therapeutic agent for autoimmune diseases via a variety of mechanisms. Effector memory T cells (T(EM), CCR7⁻ CD45RO⁺ T lymphocyte) have been demonstrated to play a crucial role in the pathogenesis of T cell-mediated autoimmune diseases, such as multiple sclerosis (MS) or rheumatoid arthritis (RA). Kv1.3 channels are predominantly expressed in T(EM) cells and control T(EM) activities. In the present study, we examined the effect of curcumin on human Kv1.3 (hKv1.3) channels stably expressed in HEK-293 cells and its ability to inhibit proliferation and cytokine secretion of T(EM) cells isolated from patients with MS or RA. Curcumin exhibited a direct blockage of hKv1.3 channels in a time-dependent and concentration-dependent manner. Moreover, the activation curve was shifted to a more positive potential, which was consistent with an open-channel blockade. Paralleling hKv1.3 inhibition, curcumin significantly inhibited proliferation and interferon-γ secretion of T(EM) cells. Our findings demonstrate that curcumin is able to inhibit proliferation and proinflammatory cytokine secretion of T(EM) cells probably through inhibition of hKv1.3 channels, which contributes to the potency of curcumin for the treatment of autoimmune diseases. This is probably one of pharmacological mechanisms of curcumin used to treat autoimmune diseases. PMID:23132777

  2. Joint HVAC Transmission EMF Environmental Study : Final Report on Experiment 1.

    SciTech Connect

    United States. Bonneville Power Administration; Oregon Regional Primate Research Center

    1992-05-01

    This document describes the rationale, procedures, and results of a carefully controlled study conducted to establish whether chronic exposure of female (ewe) Suffolk lambs to the environment of a 500-kV 60-Hz transmission line would affect various characteristics of growth, endocrine function, and reproductive development. This experiment used identical housing and management schemes for control and line-exposed ewes, thus minimizing these factors as contributors to between-group experimental error. Further, throughout the 10-month duration of this study, changes in electric and magnetic fields, audible noise, and weather conditions were monitored continuously by a computerized system. Such measurements provided the opportunity to identify any relationship between environmental factors and biological responses. Because of reports in the literature that electric and magnetic fields alter concentrations of melatonin in laboratory animals, the primary objective of this study was to ascertain whether a similar effect occurs in lambs exposed to a 500-kV a-c line in a natural setting. In addition, onset of puberty, changes in body weight, wool growth, and behavior were monitored. To determine whether the environment of a 500-kV line caused stress in the study animals, serum levels of cortisol were measured. The study was conducted at Bonneville Power Administration`s Ostrander Substation near Estacada, Oregon.

  3. Sub-Angstrom Low Voltage Performance of a Monochromated, Aberration-Corrected Transmission Electron Microscope

    PubMed Central

    Bell, David C.; Russo, Christopher J.; Benner, Gerd

    2011-01-01

    Lowering the electron energy in the transmission electron microscope allows for a significant improvement in contrast of light elements, and reduces knock-on damage for most materials. If low-voltage electron microscopes are defined as those with accelerating voltages below 100 kV, the introduction of aberration correctors and monochromators to the electron microscope column enables Ångstrom-level resolution, which was previously reserved for higher voltage instruments. Decreasing electron energy has three important advantages: 1) knock-on damage is lower, which is critically important for sensitive materials such as graphene and carbon nanotubes; 2) cross sections for electron-energy-loss spectroscopy increase, improving signal-to-noise for chemical analysis; 3) elastic scattering cross sections increase, improving contrast in high-resolution, zero-loss images. The results presented indicate that decreasing the acceleration voltage from 200 kV to 80 kV in a monochromated, aberration-corrected microscope enhances the contrast while retaining sub-angstrom resolution. These improvements in low-voltage performance are expected to produce many new results and enable a wealth of new experiments in materials science. PMID:20598206

  4. Rearrangements in the Relative Orientation of Cytoplasmic Domains Induced by a Membrane-anchored Protein Mediate Modulations in Kv Channel Gating*

    PubMed Central

    Lvov, Anatoli; Greitzer, Dafna; Berlin, Shai; Chikvashvili, Dodo; Tsuk, Sharon; Lotan, Ilana; Michaelevski, Izhak

    2009-01-01

    Interdomain interactions between intracellular N and C termini have been described for various K+ channels, including the voltage-gated Kv2.1, and suggested to affect channel gating. However, no channel regulatory protein directly affecting N/C interactions has been demonstrated. Most Kv2.1 channel interactions with regulatory factors occur at its C terminus. The vesicular SNARE that is also present at a high concentration in the neuronal plasma membrane, VAMP2, is the only protein documented to affect Kv2.1 gating by binding to its N terminus. As its binding target has been mapped near a site implicated in Kv2.1 N/C interactions, we hypothesized that VAMP2 binding to the N terminus requires concomitant conformational changes in the C terminus, which wraps around the N terminus from the outside, to give VAMP2 access. Here, we first determined that the Kv2.1 N terminus, although crucial, is not sufficient to convey functional interaction with VAMP2, and that, concomitant to its binding to the “docking loop” at the Kv2.1 N terminus, VAMP2 binds to the proximal part of the Kv2.1 C terminus, C1a. Next, using computational biology approaches (ab initio modeling, docking, and molecular dynamics simulations) supported by molecular biology, biochemical, electrophysiological, and fluorescence resonance energy transfer analyses, we mapped the interaction sites on both VAMP2 and Kv2.1 and found that this interaction is accompanied by rearrangements in the relative orientation of Kv2.1 cytoplasmic domains. We propose that VAMP2 modulates Kv2.1 inactivation by interfering with the interaction between the docking loop and C1a, a mechanism for gating regulation that may pertain also to other Kv channels. PMID:19690160

  5. A Role for Myosin V Motor Proteins in the Selective Delivery of Kv Channel Isoforms to the Membrane Surface of Cardiac Myocytes

    PubMed Central

    Schumacher-Bass, Sarah M.; Vesely, Eileen D.; Zhang, Lian; Ryland, Katherine E.; McEwen, Dyke P.; Chan, Priscilla J.; Frasier, Chad R.; McIntyre, Jeremy C.; Shaw, Robin M.; Martens, Jeffrey R.

    2014-01-01

    Rationale Kv1.5 (KCNA5) mediates the IKur current that controls atrial action potential duration. Given its atrial-specific expression and alterations in human atrial fibrillation (AF), Kv1.5 has emerged as a promising target for the treatment of AF. A necessary step in the development of novel agents that selectively modulate trafficking pathways is the identification of the cellular machinery controlling Kv1.5 surface density, of which little is yet known. Objective To investigate the role of the unconventional myosin V (MYO5A and MYO5B) motors in determining the cell surface density of Kv1.5. Methods and Results Western Blot analysis showed MYO5A and MYO5B expression in the heart, while disruption of endogenous motors selectively reduced IKur current in adult rat cardiomyocytes. Dominant negative constructs and shRNA silencing demonstrated a role for MYO5A and MYO5B in the surface trafficking of Kv1.5 and Connexin-43 (Cx43), but not hERG (KCNH2). Live-cell imaging of Kv1.5-GFP and retrospective labeling of phalloidin demonstrated motility of Kv1.5 vesicles on actin tracts. MYO5A participated in anterograde trafficking, while MYO5B regulated post-endocytic recycling. Over-expression of mutant motors revealed a selective role for Rab11 in coupling MYO5B to Kv1.5 recycling. Conclusions MYO5A and MYO5B control functionally distinct steps in the surface trafficking of Kv1.5. These isoform-specific trafficking pathways determine Kv1.5-encoded IKur in myocytes to regulate repolarizing current, and consequently, cardiac excitability. Therapeutic strategies that manipulate Kv1.5 selective trafficking pathways may prove useful in the treatment of arrhythmias. PMID:24508725

  6. Serotonin contracts the rat mesenteric artery by inhibiting 4-aminopyridine-sensitive Kv channels via the 5-HT2A receptor and Src tyrosine kinase.

    PubMed

    Sung, Dong Jun; Noh, Hyun Ju; Kim, Jae Gon; Park, Sang Woong; Kim, Bokyung; Cho, Hana; Bae, Young Min

    2013-01-01

    Serotonin (5-hydroxytryptamine (5-HT)) is a neurotransmitter that regulates a variety of functions in the nervous, gastrointestinal and cardiovascular systems. Despite such importance, 5-HT signaling pathways are not entirely clear. We demonstrated previously that 4-aminopyridine (4-AP)-sensitive voltage-gated K(+) (Kv) channels determine the resting membrane potential of arterial smooth muscle cells and that the Kv channels are inhibited by 5-HT, which depolarizes the membranes. Therefore, we hypothesized that 5-HT contracts arteries by inhibiting Kv channels. Here we studied 5-HT signaling and the detailed role of Kv currents in rat mesenteric arteries using patch-clamp and isometric tension measurements. Our data showed that inhibiting 4-AP-sensitive Kv channels contracted arterial rings, whereas inhibiting Ca(2+)-activated K(+), inward rectifier K(+) and ATP-sensitive K(+) channels had little effect on arterial contraction, indicating a central role of Kv channels in the regulation of resting arterial tone. 5-HT-induced arterial contraction decreased significantly in the presence of high KCl or the voltage-gated Ca(2+) channel (VGCC) inhibitor nifedipine, indicating that membrane depolarization and the consequent activation of VGCCs mediate the 5-HT-induced vasoconstriction. The effects of 5-HT on Kv currents and arterial contraction were markedly prevented by the 5-HT2A receptor antagonists ketanserin and spiperone. Consistently, α-methyl 5-HT, a 5-HT2 receptor agonist, mimicked the 5-HT action on Kv channels. Pretreatment with a Src tyrosine kinase inhibitor, 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine, prevented both the 5-HT-mediated vasoconstriction and Kv current inhibition. Our data suggest that 4-AP-sensitive Kv channels are the primary regulator of the resting tone in rat mesenteric arteries. 5-HT constricts the arteries by inhibiting Kv channels via the 5-HT2A receptor and Src tyrosine kinase pathway. PMID:24336234

  7. Slowing heterosexual HIV transmission.

    PubMed

    Ronald, A R

    1995-06-01

    HIV-1 is spreading rapidly through heterosexual intercourse in many societies. Slowing the transmission of this virus is the most urgent global public health priority. Our understanding of the biologic differences between societies that account for most vacancies in heterosexual HIV transmission are now understood. Effective interventions to slow transmission must be designed, implemented, and evaluated. Human and fiscal resources must be provided through a shared global effort. The consequences of failing to do so will lead to a world catastrophe of unprecedented magnitude. PMID:7673667

  8. The voltage profile improvement using static var compensator (SVC) in power system transmission

    NASA Astrophysics Data System (ADS)

    Ramdan, G. M.; Mulyadi, Y.; Hasbullah

    2016-04-01

    In transmission system named ‘Subsistem Bandung Selatan dan New Ujungberung’ there are the voltage drop which relatively high and the voltage profile at the receiving ends below 0.95 p.u. Therefore, this research proposed a method to improve the voltage profile in the transmission system using one of Flexible Alternating Current Transmission System (FACTS) technology which is Static Var Compensator (SVC) and ‘Subsistem Bandung Selatan and New Ujungberung’ as the object. This research aims to get the voltage profile in ‘Subsistem Bandung Selatan dan New Ujungberung’ before and after connected to SVC and to set optimal location and rating of SVC to maintain the voltage profile at the system that has desire range (0.95 p.u - 1.05 p.u). To get the result in accordance with these objects, Newton -Raphson power flow solution is applied to the system. The result of Newton- Raphson power flow solution of the system shows the voltage profile before connecting to SVC are averagely 140.95 kV or 0.94 p.u while after connecting to SVC are 145.28 kV or 0.97 p.u. The SVC installation is connected to ‘Bandung Utara I’ as the weakest bus, and the SVC rating is -250 Mvar to 300 Mvar.

  9. Tractor Transmissions. A Teaching Reference.

    ERIC Educational Resources Information Center

    American Association for Agricultural Engineering and Vocational Agriculture, Athens, GA.

    The manual was developed as a reference for teaching students about transmissions in farm tractors. The manual is divided into five sections: (1) transmission history, (2) gears and bearings in transmission, (3) sliding-gear transmissions, (4) planetary gearing, and (5) glossary. The working principles of the sliding-gear transmission, the most…

  10. Transmission Cost Allocation Methodologies for Regional Transmission Organizations

    SciTech Connect

    Fink, S.; Rogers, J.; Porter, K.

    2010-07-01

    This report describes transmission cost allocation methodologies for transmission projects developed to maintain or enhance reliability, to interconnect new generators, or to access new resources and enhance competitive bulk power markets, otherwise known as economic transmission projects.

  11. Backscattered radiation into a transmission ionization chamber: measurement and Monte Carlo simulation.

    PubMed

    Yoshizumi, Maíra T; Yoriyaz, Hélio; Caldas, Linda V E

    2010-01-01

    Backscattered radiation (BSR) from field-defining collimators can affect the response of a monitor chamber in X-radiation fields. This contribution must be considered since this kind of chamber is used to monitor the equipment response. In this work, the dependence of a transmission ionization chamber response on the aperture diameter of the collimators was studied experimentally and using a Monte Carlo (MC) technique. According to the results, the BSR increases the chamber response of over 4.0% in the case of a totally closed collimator and 50 kV energy beam, using both techniques. The results from Monte Carlo simulation confirm the validity of the simulated geometry.

  12. Scanning image detection (SID) system for conventional transmission electron microscope (CTEM) images.

    PubMed

    Tanji, T; Tomita, M; Kobayashi, H

    1990-08-01

    A new image detection system has been developed to display transmission electron microscope (TEM) images on a CRT without a video camera system. Deflection coils placed in both the upper space of an objective lens and in the lower space of the first intermediate lens scan a small electron probe simultaneously. The electrical signal acquired through an improved scintillator and a photomultiplier is synchronized with the scanning signal and displayed in a similar fashion to a conventional scanning TEM (STEM) instrument. A preliminary system using a 100 kV conventional TEM (CTEM) equipped with a hairpin-type electron gun, produced an image with a spatial resolution of 1 nm.

  13. Down hole transmission system

    DOEpatents

    Hall, David R.; Hall, Jr., H. Tracy

    2007-07-24

    A transmission system in a downhole component comprises a data transmission element in both ends of the downhole component. Each data transmission element houses an electrically conducting coil in a MCEI circular trough. The electrically conducting coil comprises at least two generally fractional loops. In the preferred embodiment, the transmission elements are connected by an electrical conductor. Preferably, the electrical conductor is a coaxial cable. Preferably, the MCEI trough comprises ferrite. In the preferred embodiment, the fractional loops are connected by a connecting cable. In one aspect of the present invention, the connecting cable is a pair of twisted wires. In one embodiment the connecting cable is a shielded pair of twisted wires. In another aspect of the present invention, the connecting cable is a coaxial cable. The connecting cable may be disposed outside of the MCEI circular trough.

  14. Preselected multiratio transmission

    SciTech Connect

    Mahoney, J.E.

    1986-09-09

    A multistep ratio power transmission is described comprising a drive shaft; a driven shaft; three selectively engageable friction clutch means operatively connected with the drive shaft; three transmission input shafts each connected with respective friction clutch means. Three synchronizer clutch means are connected with respective ones of the three transmission input shafts; gear train means operatively connected with the output shaft for selectively providing forward step ratios and a reverse ratio including two ratio gears on each transmission input shaft and being selectively connectible therewith by respective ones of the synchronizer clutch means, and an output ratio gear meshing with each ratio gear; and each of the synchronizer clutch means being operable to selectively connect a pair of gear train means with the respective friction clutch means. At least two of the pairs of gear train means provide forward drive ratio with each pair controlled by the same synchronizer clutch means providing forward drive ratios which are separated by three ratio steps.

  15. Multiplex television transmission system

    NASA Technical Reports Server (NTRS)

    Reed, W. R.

    1967-01-01

    Time-multiplexing system enables several cameras to share a single commercial television transmission channel. This system is useful in industries for visually monitoring several operating areas or instrument panels from a remote location.

  16. Transmission of Flu (Influenza)

    MedlinePlus

    ... Skip Content Marketing Share this: Main Content Area Flu (Influenza) Transmission How Flu Spreads Coughing and Sneezing People with flu can ... not be shared without washing thoroughly first. The Flu Is Contagious You may be able to pass ...

  17. Downhole transmission system

    DOEpatents

    Hall, David R.; Fox, Joe

    2008-01-15

    A transmission system in a downhole component comprises a data transmission element in both ends of the downhole component. Each data transmission element houses an electrically conducting coil in a MCEI circular trough. An electrical conductor connects both the transmission elements. The electrical conductor comprises at least three electrically conductive elements insulated from each other. In the preferred embodiment the electrical conductor comprises an electrically conducting outer shield, an electrically conducting inner shield and an electrical conducting core. In some embodiments of the present invention, the electrical conductor comprises an electrically insulating jacket. In other embodiments, the electrical conductor comprises a pair of twisted wires. In some embodiments, the electrical conductor comprises semi-conductive material.

  18. Gravity wave transmission diagram

    NASA Astrophysics Data System (ADS)

    Tomikawa, Yoshihiro

    2016-07-01

    A possibility of gravity wave propagation from a source region to the airglow layer around the mesopause has been discussed based on the gravity wave blocking diagram taking into account the critical level filtering alone. This paper proposes a new gravity wave transmission diagram in which both the critical level filtering and turning level reflection of gravity waves are considered. It shows a significantly different distribution of gravity wave transmissivity from the blocking diagram.

  19. Continuously Variable Transmission

    NASA Technical Reports Server (NTRS)

    Grana, D. C.

    1985-01-01

    Chain slides along two cones, in novel transmission concept. Transmission includes chain drive between two splined shafts. Chain sprockets follow surfaces of two cones. As one chain sprocket moves toward smaller diameter other chain sprocket moves toward larger diameter, thereby changing "gear" ratio. Movement initiated by tension applied to chain by planetary gear mechanism. Device positive, simple, and efficient over wide range of speed ratios.

  20. Multistate differential transmission

    SciTech Connect

    Whalen, B.

    1987-09-01

    A multistate transmission is described having an input shaft and an output shaft comprising: a. planetary gear train means having a ring gear, planetary gears with planetary gear carrier, and a sun gear, the planetary gear train means connected to the output shaft; b. first bypass means connecting the input shaft to the planetary gear train means; c. differential transmission means for receiving its input from the input shaft and having means to adjust the torque and speed output infinitely variable over its range of operation for each state of the transmission; d. power return means for receiving the output of the differential transmission means; e. means including clutch operated speed reversing means for interconnecting the sun gear in the planetary gear train means with the power return means; f. the power return means including a first gear to receive the output of the differential transmission means; g. first multispeed transmission means connecting the means for supporting the carrier shaft to the first bypass means.

  1. National transmission grid study

    SciTech Connect

    Abraham, Spencer

    2003-05-31

    The National Energy Policy Plan directed the U.S. Department of Energy (DOE) to conduct a study to examine the benefits of establishing a national electricity transmission grid and to identify transmission bottlenecks and measures to address them. DOE began by conducting an independent analysis of U.S. electricity markets and identifying transmission system bottlenecks using DOE’s Policy Office Electricity Modeling System (POEMS). DOE’s analysis, presented in Section 2, confirms the central role of the nation’s transmission system in lowering costs to consumers through increased trade. More importantly, DOE’s analysis also confirms the results of previous studies, which show that transmission bottlenecks and related transmission system market practices are adding hundreds of millions of dollars to consumers’ electricity bills each year. A more detailed technical overview of the use of POEMS is provided in Appendix A. DOE led an extensive, open, public input process and heard a wide range of comments and recommendations that have all been considered.1 More than 150 participants registered for three public workshops held in Detroit, MI (September 24, 2001); Atlanta, GA (September 26, 2001); and Phoenix, AZ (September 28, 2001).

  2. Closed-state inactivation involving an internal gate in Kv4.1 channels modulates pore blockade by intracellular quaternary ammonium ions.

    PubMed

    Fineberg, Jeffrey D; Szanto, Tibor G; Panyi, Gyorgy; Covarrubias, Manuel

    2016-01-01

    Voltage-gated K(+) (Kv) channel activation depends on interactions between voltage sensors and an intracellular activation gate that controls access to a central pore cavity. Here, we hypothesize that this gate is additionally responsible for closed-state inactivation (CSI) in Kv4.x channels. These Kv channels undergo CSI by a mechanism that is still poorly understood. To test the hypothesis, we deduced the state of the Kv4.1 channel intracellular gate by exploiting the trap-door paradigm of pore blockade by internally applied quaternary ammonium (QA) ions exhibiting slow blocking kinetics and high-affinity for a blocking site. We found that inactivation gating seemingly traps benzyl-tributylammonium (bTBuA) when it enters the central pore cavity in the open state. However, bTBuA fails to block inactivated Kv4.1 channels, suggesting gated access involving an internal gate. In contrast, bTBuA blockade of a Shaker Kv channel that undergoes open-state P/C-type inactivation exhibits fast onset and recovery inconsistent with bTBuA trapping. Furthermore, the inactivated Shaker Kv channel is readily blocked by bTBuA. We conclude that Kv4.1 closed-state inactivation modulates pore blockade by QA ions in a manner that depends on the state of the internal activation gate. PMID:27502553

  3. BmP02 Atypically Delays Kv4.2 Inactivation: Implication for a Unique Interaction between Scorpion Toxin and Potassium Channel

    PubMed Central

    Wu, Bin; Zhu, Yan; Shi, Jian; Tao, Jie; Ji, Yonghua

    2016-01-01

    BmP02, a short-chain peptide with 28 residues from the venom of Chinese scorpion Buthus martensi Karsch, has been reported to inhibit the transient outward potassium currents (Ito) in rat ventricular muscle cells. However, it remains unclear whether BmP02 modulates the Kv4.2 channel, one of the main contributors to Ito. The present study investigated the effects of BmP02 on Kv4.2 kinetics and its underlying molecular mechanism. The electrophysiological recordings showed that the inactivation of Kv4.2 expressed in HEK293T cells was significantly delayed by BmP02 in a dose-response manner with EC50 of ~850 nM while the peak current, activation and voltage-dependent inactivation of Kv4.2 were not affected. Meanwhile, the recovery from inactivation of Kv4.2 was accelerated and the deactivation was slowed after the application of BmP02. The site-directed mutagenesis combined with computational modelling identified that K347 and K353, located in the turret motif of the Kv4.2, and E4/E5, D20/D21 in BmP02 are key residues to interact with BmP02 through electrostatic force. These findings not only reveal a novel interaction between Kv4.2 channel and its peptidyl modulator, but also provide valuable information for design of highly-selective Kv4.2 modulators. PMID:27690098

  4. Closed-state inactivation involving an internal gate in Kv4.1 channels modulates pore blockade by intracellular quaternary ammonium ions

    PubMed Central

    Fineberg, Jeffrey D.; Szanto, Tibor G.; Panyi, Gyorgy; Covarrubias, Manuel

    2016-01-01

    Voltage-gated K+ (Kv) channel activation depends on interactions between voltage sensors and an intracellular activation gate that controls access to a central pore cavity. Here, we hypothesize that this gate is additionally responsible for closed-state inactivation (CSI) in Kv4.x channels. These Kv channels undergo CSI by a mechanism that is still poorly understood. To test the hypothesis, we deduced the state of the Kv4.1 channel intracellular gate by exploiting the trap-door paradigm of pore blockade by internally applied quaternary ammonium (QA) ions exhibiting slow blocking kinetics and high-affinity for a blocking site. We found that inactivation gating seemingly traps benzyl-tributylammonium (bTBuA) when it enters the central pore cavity in the open state. However, bTBuA fails to block inactivated Kv4.1 channels, suggesting gated access involving an internal gate. In contrast, bTBuA blockade of a Shaker Kv channel that undergoes open-state P/C-type inactivation exhibits fast onset and recovery inconsistent with bTBuA trapping. Furthermore, the inactivated Shaker Kv channel is readily blocked by bTBuA. We conclude that Kv4.1 closed-state inactivation modulates pore blockade by QA ions in a manner that depends on the state of the internal activation gate. PMID:27502553

  5. Supplement Analysis for the Transmission System Vegetation Management Program FEIS (DOE/EIS-0285/SA-141- Salem Albany #2)

    SciTech Connect

    Barndt, Shawn L.

    2003-04-04

    Vegetation Management for the Salem Albany #2 115 kV transmission line from Salem Substation to Albany Substation. BPA proposes to remove unwanted vegetation along the right-of-way, access roads, switch platforms, microwave beam paths, and around tower structures of the subject transmission line corridor that may impede the operation and maintenance of the identified transmission lines. BPA plans to conduct vegetation control with the goal of removing tall growing vegetation that is currently or will soon be a hazard to the transmission line. BPA’s overall goal is to have low-growing plant communities along the rights-of-way to control the development of potentially threatening vegetation.

  6. An all solid-state high-voltage ns trigger generator based on magnetic pulse compression and transmission line transformer.

    PubMed

    Lin, Jiajin; Yang, Jianhua; Zhang, Jiande; Chen, Xinbing

    2013-09-01

    Innovative design of an all solid-state high-voltage ns trigger generator, based on magnetic pulse compression and transmission line transformer, is presented. The repetitive trigger pulse generator was developed to trigger a 700 kV trigatron, which has been used to pulse a repetitive intense electron beam accelerator with Tesla transformer charged double pulse forming lines (PFLs). Experimental results show that the trigger pulse generator could produce 180 kV 65 ns duration pulses with a rise time of 20 ns. The repetitive trigger pulses have nice uniform in the voltage waveform. The control time jitter is less then 3 ns. Owing to its good stability and low time jitter, the high-voltage trigger generator is an excellent candidate to trigger the repetitive accelerator.

  7. Preliminary study on development of 300 Kv compact focused gaseous ion beam system

    SciTech Connect

    Ohkubo, T.; Ishii, Y.; Kamiya, T.; Miyake, Y.

    2013-04-19

    A new 300 kV compact focused gaseous ion beam (gas-FIB) system with three-stage acceleration lens was constructed at JAEA. The preliminary experiments of formation of the focused gaseous ion beams were carried out to show the availability of the gas-FIB system as a writing tool for 3D proton lithography. As a result of the experiments, it was proved that the focal point was kept at the same position under changing the kinetic energy but with keeping the kinetic energy ratio constant, which was defined as the ratio of kinetic energy in object side to that in image side for the third acceleration lens. This characteristic of the gas-FIB is a good point to advance the 3D proton lithography changing penetration depth in a sample by varying the beam energy.

  8. A folding zone in the ribosomal exit tunnel for Kv1.3 helix formation.

    PubMed

    Tu, Li Wei; Deutsch, Carol

    2010-03-12

    Although it is now clear that protein secondary structure can be acquired early, while the nascent peptide resides within the ribosomal exit tunnel, the principles governing folding of native polytopic proteins have not yet been elucidated. We now report an extensive investigation of native Kv1.3, a voltage-gated K(+) channel, including transmembrane and linker segments synthesized in sequence. These native segments form helices vectorially (N- to C-terminus) only in a permissive vestibule located in the last 20 A of the tunnel. Native linker sequences similarly fold in this vestibule. Finally, secondary structure acquired in the ribosome is retained in the translocon. These findings emerge from accessibility studies of a diversity of native transmembrane and linker sequences and may therefore be applicable to protein biogenesis in general.

  9. Extending the service life of 15KV polyethylene URD cable using silicone liquid

    SciTech Connect

    Kirkham, H.; Johnston, A.R. )

    1989-10-01

    This paper describes methods and materials used to extend the useful life ot extruded polyethylene insulated cables rated 15KV that have developed electrochemical trees in the insulation of sufficient severity to cause service failures. Earlier rehabilitation methods treated extruded dielectric cable with both gases and insulating liquids. This new method fills the cable and impregnates the insulation with a silicone liquid. This liquid, which is reactive, significantly improves the voltage breakdown strength of the cables, which has been reduced by electrochemical trees, and extends the useful service life of the cable. A review of the criteria used to develop the silicone liquid for this application and the methodology used to inject it into the cable will be discussed. An assessment of the costs of this life extension indicates a significantly lower cost than conventional cable replacement with little disturbance to the service and property of the customer.

  10. Study on 12kV outdoor vacuum switch with replaceable HRC element drop out fuse

    SciTech Connect

    Wang Jiimei

    1996-12-31

    A new type of vacuum interrupter for 12kV outdoor vacuum switch was experimentally studied, the envelope of which was made of porcelain with petticoat flange for outdoor insulation. In order to produce an axial magnetic field and improve the capacity of transfer current in the vacuum interrupter, an iron plate of horse-shoe construction ingeniously designed was chosen as an electrode. The drop-out fuse with replaceable sand-filled HRC element in series with the vacuum switch is a new conception of design to increase breaking capacity. However, it is a vacuum switch of newly designed to form {open_quotes}a vacuum switch and drop-out type fuse combination{close_quotes}.

  11. A Folding Zone in the Ribosomal Exit Tunnel for Kv1.3 Helix Formation

    PubMed Central

    Tu, LiWei; Deutsch, Carol

    2010-01-01

    SUMMARY Although it is now clear that protein secondary structure can be acquired early, while the nascent peptide resides within the ribosomal exit tunnel, the principles governing folding of native polytopic proteins have not yet been elucidated. We now report an extensive investigation of native Kv1.3, a voltage-gated K+ channel, including transmembrane and linker segments synthesized in sequence. These native segments form helices vectorially (N- to C-terminus) only in a permissive vestibule located in the last 20Å of the tunnel. Native linker sequences similarly fold in this vestibule. Finally, secondary structure acquired in the ribosome is retained in the translocon. These findings emerge from accessibility studies of a diversity of native transmembrane and linker sequences and may therefore be applicable to protein biogenesis in general. PMID:20060838

  12. Comparative evaluation by laboratory aging of 15 and 35 kV extruded dielectric cables

    SciTech Connect

    Katz, C.; Dyndul, J. ); Walker, M. )

    1990-04-01

    Utility engineers encounter a significant problem in discerning the accuracy of claims made of superior cable quality and in identifying cables which will provide reliable performance over their anticipated life. The authors in two independent investigations of 15 and 35 kV cables have compared the performance of a number of cables made with different compounds, by different manufacturers. They show that judging cables by their unaged voltage breakdown characteristics alone can be very misleading; that in the long run, dry cured cables, aged in moist environments, rapidly lose their original dielectric strength advantage; that certain ethylene propylene rubber formulations degrade as fast as crosslinked polyethylene; that the best overall results during aging are obtained with tree resistant polyethylene insulated cables and that from a voltage breakdown point of view water tree length is more influential than number of water trees.

  13. Simulation of ion beam transport through the 400 Kv ion implanter at Michigan Ion Beam Laboratory

    NASA Astrophysics Data System (ADS)

    Naab, F. U.; Toader, O. F.; Was, G. S.

    2013-04-01

    The Michigan Ion Beam Laboratory houses a 400 kV ion implanter. An application that simulates the ion beam trajectories through the implanter from the ion source to the target was developed using the SIMION® code. The goals were to have a tool to develop an intuitive understanding of abstract physics phenomena and diagnose ion trajectories. Using this application, new implanter users of different fields in science quickly understand how the machine works and quickly learn to operate it. In this article we describe the implanter simulation application and compare the parameters of the implanter components obtained from the simulations with the measured ones. The overall agreement between the simulated and measured values of magnetic fields and electric potentials is ˜10%.

  14. Radio frequency induction plasma generator 80-kV test stand operation

    SciTech Connect

    Goede, H.; DiVergilio, W.F.; Fosnight, V.V.; Vella, M.C.; Ehlers, K.W.; Kippenhan, D.; Pincosy, P.A.; Pyle, R.V.

    1986-07-01

    Beam extraction tests at energies up to 80 kV were performed using a radio frequency induction (RFI) plasma generator hydrogen ion source. A 7 x 10-cm/sup 2/, long pulse accelerator was operated with a 10 x 10-cm/sup 2/ axial magnetic cusp bucket and a magnetic-filter bucket. Atomic fractions (up to 85% H/sup +/), plasma production efficiencies (roughly-equal0.6 A of beam per kW rf power), and beam divergence were at least as good as with arc plasmas in similar chambers. Potential advantages of the RFI plasma sources for large-scale applications are ease of operation, reliability, and extended service life.

  15. Novel phenotype associated with a mutation in the KCNA1(Kv1.1) gene

    PubMed Central

    D'Adamo, Maria C.; Gallenmüller, Constanze; Servettini, Ilenio; Hartl, Elisabeth; Tucker, Stephen J.; Arning, Larissa; Biskup, Saskia; Grottesi, Alessandro; Guglielmi, Luca; Imbrici, Paola; Bernasconi, Pia; Di Giovanni, Giuseppe; Franciolini, Fabio; Catacuzzeno, Luigi; Pessia, Mauro; Klopstock, Thomas

    2015-01-01

    Episodic ataxia type 1 (EA1) is an autosomal dominant K+ channelopathy which manifests with short attacks of cerebellar ataxia and dysarthria, and may also show interictal myokymia. Episodes can be triggered by emotional or physical stress, startle response, sudden postural change or fever. Here we describe a 31-year-old man displaying markedly atypical symptoms, including long-lasting attacks of jerking muscle contractions associated with hyperthermia, severe migraine, and a relatively short-sleep phenotype. A single nucleotide change in KCNA1 (c.555C>G) was identified that changes a highly conserved residue (p.C185W) in the first transmembrane segment of the voltage-gated K+ channel Kv1.1. The patient is heterozygous and the mutation was inherited from his asymptomatic mother. Next generation sequencing revealed no variations in the CACNA1A, CACNB4, KCNC3, KCNJ10, PRRT2 or SCN8A genes of either the patient or mother, except for a benign variant in SLC1A3. Functional analysis of the p.C185W mutation in KCNA1 demonstrated a deleterious dominant-negative phenotype where the remaining current displayed slower activation kinetics, subtle changes in voltage-dependence and faster recovery from slow inactivation. Structural modeling also predicts the C185W mutation to be functionally deleterious. This description of novel clinical features, associated with a Kv1.1 mutation highlights a possibly unrecognized relationship between K+ channel dysfunction, hyperthermia and migraine in EA1, and suggests that thorough assessments for these symptoms should be carefully considered for all patients affected by EA1. PMID:25642194

  16. Stabilization of the conductive conformation of a voltage-gated K+ (Kv) channel: the lid mechanism.

    PubMed

    Santos, Jose S; Syeda, Ruhma; Montal, Mauricio

    2013-06-01

    Voltage-gated K(+) (Kv) channels are molecular switches that sense membrane potential and in response open to allow K(+) ions to diffuse out of the cell. In these proteins, sensor and pore belong to two distinct structural modules. We previously showed that the pore module alone is a robust yet dynamic structural unit in lipid membranes and that it senses potential and gates open to conduct K(+) with unchanged fidelity. The implication is that the voltage sensitivity of K(+) channels is not solely encoded in the sensor. Given that the coupling between sensor and pore remains elusive, we asked whether it is then possible to convert a pore module characterized by brief openings into a conductor with a prolonged lifetime in the open state. The strategy involves selected probes targeted to the filter gate of the channel aiming to modulate the probability of the channel being open assayed by single channel recordings from the sensorless pore module reconstituted in lipid bilayers. Here we show that the premature closing of the pore is bypassed by association of the filter gate with two novel open conformation stabilizers: an antidepressant and a peptide toxin known to act selectively on Kv channels. Such stabilization of the conductive conformation of the channel is faithfully mimicked by the covalent attachment of fluorescein at a cysteine residue selectively introduced near the filter gate. This modulation prolongs the occupancy of permeant ions at the gate. It is this longer embrace between ion and gate that we conjecture underlies the observed stabilization of the conductive conformation. This study provides a new way of thinking about gating.

  17. SU-E-J-15: Automatically Detect Patient Treatment Position and Orientation in KV Portal Images

    SciTech Connect

    Qiu, J; Yang, D

    2015-06-15

    Purpose: In the course of radiation therapy, the complex information processing workflow will Result in potential errors, such as incorrect or inaccurate patient setups. With automatic image check and patient identification, such errors could be effectively reduced. For this purpose, we developed a simple and rapid image processing method, to automatically detect the patient position and orientation in 2D portal images, so to allow automatic check of positions and orientations for patient daily RT treatments. Methods: Based on the principle of portal image formation, a set of whole body DRR images were reconstructed from multiple whole body CT volume datasets, and fused together to be used as the matching template. To identify the patient setup position and orientation shown in a 2D portal image, the 2D portal image was preprocessed (contrast enhancement, down-sampling and couch table detection), then matched to the template image so to identify the laterality (left or right), position, orientation and treatment site. Results: Five day’s clinical qualified portal images were gathered randomly, then were processed by the automatic detection and matching method without any additional information. The detection results were visually checked by physicists. 182 images were correct detection in a total of 200kV portal images. The correct rate was 91%. Conclusion: The proposed method can detect patient setup and orientation quickly and automatically. It only requires the image intensity information in KV portal images. This method can be useful in the framework of Electronic Chart Check (ECCK) to reduce the potential errors in workflow of radiation therapy and so to improve patient safety. In addition, the auto-detection results, as the patient treatment site position and patient orientation, could be useful to guide the sequential image processing procedures, e.g. verification of patient daily setup accuracy. This work was partially supported by research grant from

  18. Characterization of scattered radiation in kV CBCT images using Monte Carlo simulations

    SciTech Connect

    Jarry, Genevieve; Graham, Sean A.; Moseley, Douglas J.; Jaffray, David J.; Siewerdsen, Jeffrey H.; Verhaegen, Frank

    2006-11-15

    Kilovoltage (kV) cone beam computed tomography (CBCT) images suffer from a substantial scatter contribution. In this study, Monte Carlo (MC) simulations are used to evaluate the scattered radiation present in projection images. These predicted scatter distributions are also used as a scatter correction technique. Images were acquired using a kV CBCT bench top system. The EGSnrc MC code was used to model the flat panel imager, the phantoms, and the x-ray source. The x-ray source model was validated using first and second half-value layers (HVL) and profile measurements. The HVLs and the profile were found to agree within 3% and 6%, respectively. MC simulated and measured projection images for a cylindrical water phantom and for an anthropomorphic head phantom agreed within 8% and 10%. A modified version of the DOSXYZnrc MC code was used to score phase space files with identified scattered and primary particles behind the phantoms. The cone angle, the source-to-detector distance, the phantom geometry, and the energy were varied to determine their effect on the scattered radiation distribution. A scatter correction technique was developed in which the MC predicted scatter distribution is subtracted from the projections prior to reconstruction. Preliminary testing of the procedure was done with an anthropomorphic head phantom and a contrast phantom. Contrast and profile measurements were obtained for the scatter corrected and noncorrected images. An improvement of 3% for contrast between solid water and a liver insert and 11% between solid water and a Teflon insert were obtained and a significant reduction in cupping and streaking artifacts was observed.

  19. The endocannabinoid 2-AG controls skeletal muscle cell differentiation via CB1 receptor-dependent inhibition of Kv7 channels

    PubMed Central

    Iannotti, Fabio A.; Silvestri, Cristoforo; Mazzarella, Enrico; Martella, Andrea; Calvigioni, Daniela; Piscitelli, Fabiana; Ambrosino, Paolo; Petrosino, Stefania; Czifra, Gabriella; Bíró, Tamás; Harkany, Tibor; Taglialatela, Maurizio; Di Marzo, Vincenzo

    2014-01-01

    Little is known of the involvement of endocannabinoids and cannabinoid receptors in skeletal muscle cell differentiation. We report that, due to changes in the expression of genes involved in its metabolism, the levels of the endocannabinoid 2-arachidonoylglycerol (2-AG) are decreased both during myotube formation in vitro from murine C2C12 myoblasts and during mouse muscle growth in vivo. The endocannabinoid, as well as the CB1 agonist arachidonoyl-2-chloroethylamide, prevent myotube formation in a manner antagonized by CB1 knockdown and by CB1 antagonists, which, per se, instead stimulate differentiation. Importantly, 2-AG also inhibits differentiation of primary human satellite cells. Muscle fascicles from CB1 knockout embryos contain more muscle fibers, and postnatal mice show muscle fibers of an increased diameter relative to wild-type littermates. Inhibition of Kv7.4 channel activity, which plays a permissive role in myogenesis and depends on phosphatidylinositol 4,5-bisphosphate (PIP2), underlies the effects of 2-AG. We find that CB1 stimulation reduces both total and Kv7.4-bound PIP2 levels in C2C12 cells and inhibits Kv7.4 currents in transfected CHO cells. We suggest that 2-AG is an endogenous repressor of myoblast differentiation via CB1-mediated inhibition of Kv7.4 channels. PMID:24927567

  20. Size-based protocol optimization using automatic tube current modulation and automatic kV selection in computed tomography.

    PubMed

    MacDougall, Robert D; Kleinman, Patricia L; Callahan, Michael J

    2016-01-01

    Size-based diagnostic reference ranges (DRRs) for contrast-enhanced pediatric abdominal computed tomography (CT) have been published in order to establish practical upper and lower limits of CTDI, DLP, and SSDE. Based on these DRRs, guidelines for establishing size-based SSDE target levels from the SSDE of a standard adult by applying a linear correction factor have been published and provide a great reference for dose optimization initiatives. The necessary step of designing manufacturer-specific CT protocols to achieve established SSDE targets is the responsibility of the Qualified Medical Physicist. The task is straightforward if fixed-mA protocols are used, however, more difficult when automatic exposure control (AEC) and automatic kV selection are considered. In such cases, the physicist must deduce the operation of AEC algorithms from technical documentation or through testing, using a wide range of phantom sizes. Our study presents the results of such testing using anthropomorphic phantoms ranging in size from the newborn to the obese adult. The effect of each user-controlled parameter was modeled for a single-manufacturer AEC algorithm (Siemens CARE Dose4D) and automatic kV selection algorithm (Siemens CARE kV). Based on the results presented in this study, a process for designing mA-modulated, pediatric abdominal CT protocols that achieve user-defined SSDE and kV targets is described. PMID:26894344

  1. Jingzhaotoxin-35, a novel gating-modifier toxin targeting both Nav1.5 and Kv2.1 channels.

    PubMed

    Wei, Peng; Xu, Changxi; Wu, Qiaoqi; Huang, Lang; Liang, Songping; Yuan, Chunhua

    2014-12-15

    Jingzhaotoxin-35 (JZTX-35), a 36-residue polypeptide, was purified from the venom of the Chinese tarantula Chilobrachys jingzhao. JZTX-35 inhibited Nav1.5 and Kv2.1 currents with the IC50 value of 1.07 μM and 3.62 μM, respectively, but showed no significant effect on either Na(+) currents or Ca(2+) currents evoked in hippocampal neurons. It shifted the activation of the Nav1.5 and Kv2.1 channels to more depolarized voltages, and markedly shifted the steady-state inactivation of Nav1.5 currents toward more hyperpolarized potentials. Moreover, JZTX-35 can bind to a close state of Nav1.5 and Kv2.1 channels. These results indicate that JZTX-35 is a new gating modifier toxin. JZTX-35 shares high sequence similarity with Jingzhaotoxins (JZTXs) targeting Nav1.5 or Kv2.1 channels, but they showed different ion channel selectivity. Structure-function analysis in this study would provide important clues for the exploration of ion channel selectivity of JZTXs. PMID:25449098

  2. Different calcium influx characteristics upon Kv1.3 and IKCa1 potassium channel inhibition in T helper subsets.

    PubMed

    Orbán, Csaba; Bajnok, Anna; Vásárhelyi, Barna; Tulassay, Tivadar; Toldi, Gergely

    2014-07-01

    Functional imbalance between T helper subsets plays important role in the pathogenesis of autoimmune disorders. Transient increase of cytoplasmic calcium level, and sustention of negative membrane potential by voltage sensitive Kv1.3 and calcium-dependent IKCa1 potassium channels are essential for short-term lymphocyte activation, thus present possible target for selective immunomodulation. We aimed to investigate calcium influx sensitivity to the inhibition of potassium channels in the main T helper subsets. Peripheral blood from 11 healthy individuals was drawn and calcium influx kinetics following activation with phytohemagglutinin in Th1, Th2, Th17, and Treg cells were evaluated. Alteration of calcium influx induced by specific inhibitors of Kv1.3 and IKCa1 potassium channels, and the expression of Kv1.3 channels were also assessed. Highest cytoplasmic calcium concentration was observed in stimulated Th1 cells, while the lowest level was measured in Treg cells. In Th1 and Th17 cells, inhibition of both investigated potassium channels decreased calcium influx. In Th2 cells only the inhibitor of Kv1.3 channels, while in Treg cells none of the inhibitors had significant effect. Upon the inhibition of IKCa1 channels, short-term activation of proinflammatory cells was specifically decreased without affecting anti-inflammatory subsets, indicating that selective immunomodulation is possible in healthy individuals.

  3. K+ channel mechanisms underlying cholinergic cutaneous vasodilation and sweating in young humans: roles of KCa, KATP, and KV channels?

    PubMed

    Fujii, Naoto; Louie, Jeffrey C; McNeely, Brendan D; Zhang, Sarah Yan; Tran, My-An; Kenny, Glen P

    2016-09-01

    Acetylcholine released from cholinergic nerves is involved in heat loss responses of cutaneous vasodilation and sweating. K(+) channels are thought to play a role in regulating cholinergic cutaneous vasodilation and sweating, though which K(+) channels are involved in their regulation remains unclear. We evaluated the hypotheses that 1) Ca(2+)-activated K(+) (KCa), ATP-sensitive K(+) (KATP), and voltage-gated K(+) (KV) channels all contribute to cholinergic cutaneous vasodilation; and 2) KV channels, but not KCa and KATP channels, contribute to cholinergic sweating. In 13 young adults (24 ± 5 years), cutaneous vascular conductance (CVC) and sweat rate were evaluated at intradermal microdialysis sites that were continuously perfused with: 1) lactated Ringer (Control), 2) 50 mM tetraethylammonium (KCa channel blocker), 3) 5 mM glybenclamide (KATP channel blocker), and 4) 10 mM 4-aminopyridine (KV channel blocker). At all sites, cholinergic cutaneous vasodilation and sweating were induced by coadministration of methacholine (0.0125, 0.25, 5, 100, and 2,000 mM, each for 25 min). The methacholine-induced increase in CVC was lower with the KCa channel blocker relative to Control at 0.0125 (1 ± 1 vs. 9 ± 6%max) and 5 (2 ± 5 vs. 17 ± 14%max) mM methacholine, whereas it was lower in the presence of KATP (69 ± 7%max) and KV (57 ± 14%max) channel blocker compared with Control (79 ± 6%max) at 100 mM methacholine. Furthermore, methacholine-induced sweating was lower at the KV channel blocker site (0.42 ± 0.17 mg·min(-1)·cm(-2)) compared with Control (0.58 ± 0.15 mg·min(-1)·cm(-2)) at 2,000 mM methacholine. In conclusion, we show that KCa, KATP, and KV channels play a role in cholinergic cutaneous vasodilation, whereas only KV channels contribute to cholinergic sweating in normothermic resting humans. PMID:27440718

  4. A fiducial detection algorithm for real-time image guided IMRT based on simultaneous MV and kV imaging

    SciTech Connect

    Mao Weihua; Riaz, Nadeem; Lee, Louis; Wiersma, Rodney; Xing Lei

    2008-08-15

    The advantage of highly conformal dose techniques such as 3DCRT and IMRT is limited by intrafraction organ motion. A new approach to gain near real-time 3D positions of internally implanted fiducial markers is to analyze simultaneous onboard kV beam and treatment MV beam images (from fluoroscopic or electronic portal image devices). Before we can use this real-time image guidance for clinical 3DCRT and IMRT treatments, four outstanding issues need to be addressed. (1) How will fiducial motion blur the image and hinder tracking fiducials? kV and MV images are acquired while the tumor is moving at various speeds. We find that a fiducial can be successfully detected at a maximum linear speed of 1.6 cm/s. (2) How does MV beam scattering affect kV imaging? We investigate this by varying MV field size and kV source to imager distance, and find that common treatment MV beams do not hinder fiducial detection in simultaneous kV images. (3) How can one detect fiducials on images from 3DCRT and IMRT treatment beams when the MV fields are modified by a multileaf collimator (MLC)? The presented analysis is capable of segmenting a MV field from the blocking MLC and detecting visible fiducials. This enables the calculation of nearly real-time 3D positions of markers during a real treatment. (4) Is the analysis fast enough to track fiducials in nearly real time? Multiple methods are adopted to predict marker positions and reduce search regions. The average detection time per frame for three markers in a 1024x768 image was reduced to 0.1 s or less. Solving these four issues paves the way to tracking moving fiducial markers throughout a 3DCRT or IMRT treatment. Altogether, these four studies demonstrate that our algorithm can track fiducials in real time, on degraded kV images (MV scatter), in rapidly moving tumors (fiducial blurring), and even provide useful information in the case when some fiducials are blocked from view by the MLC. This technique can provide a gating signal or

  5. A fiducial detection algorithm for real-time image guided IMRT based on simultaneous MV and kV imaging.

    PubMed

    Mao, Weihua; Riaz, Nadeem; Lee, Louis; Wiersma, Rodney; Xing, Lei

    2008-08-01

    The advantage of highly conformal dose techniques such as 3DCRT and IMRT is limited by intrafraction organ motion. A new approach to gain near real-time 3D positions of internally implanted fiducial markers is to analyze simultaneous onboard kV beam and treatment MV beam images (from fluoroscopic or electronic portal image devices). Before we can use this real-time image guidance for clinical 3DCRT and IMRT treatments, four outstanding issues need to be addressed. (1) How will fiducial motion blur the image and hinder tracking fiducials? kV and MV images are acquired while the tumor is moving at various speeds. We find that a fiducial can be successfully detected at a maximum linear speed of 1.6 cm/s. (2) How does MV beam scattering affect kV imaging? We investigate this by varying MV field size and kV source to imager distance, and find that common treatment MV beams do not hinder fiducial detection in simultaneous kV images. (3) How can one detect fiducials on images from 3DCRT and IMRT treatment beams when the MV fields are modified by a multileaf collimator (MLC)? The presented analysis is capable of segmenting a MV field from the blocking MLC and detecting visible fiducials. This enables the calculation of nearly real-time 3D positions of markers during a real treatment. (4) Is the analysis fast enough to track fiducials in nearly real time? Multiple methods are adopted to predict marker positions and reduce search regions. The average detection time per frame for three markers in a 1024 x 768 image was reduced to 0.1 s or less. Solving these four issues paves the way to tracking moving fiducial markers throughout a 3DCRT or IMRT treatment. Altogether, these four studies demonstrate that our algorithm can track fiducials in real time, on degraded kV images (MV scatter), in rapidly moving tumors (fiducial blurring), and even provide useful information in the case when some fiducials are blocked from view by the MLC. This technique can provide a gating signal or

  6. A fiducial detection algorithm for real-time image guided IMRT based on simultaneous MV and kV imaging

    PubMed Central

    Mao, Weihua; Riaz, Nadeem; Lee, Louis; Wiersma, Rodney; Xing, Lei

    2008-01-01

    The advantage of highly conformal dose techniques such as 3DCRT and IMRT is limited by intrafraction organ motion. A new approach to gain near real-time 3D positions of internally implanted fiducial markers is to analyze simultaneous onboard kV beam and treatment MV beam images (from fluoroscopic or electronic portal image devices). Before we can use this real-time image guidance for clinical 3DCRT and IMRT treatments, four outstanding issues need to be addressed. (1) How will fiducial motion blur the image and hinder tracking fiducials? kV and MV images are acquired while the tumor is moving at various speeds. We find that a fiducial can be successfully detected at a maximum linear speed of 1.6 cm∕s. (2) How does MV beam scattering affect kV imaging? We investigate this by varying MV field size and kV source to imager distance, and find that common treatment MV beams do not hinder fiducial detection in simultaneous kV images. (3) How can one detect fiducials on images from 3DCRT and IMRT treatment beams when the MV fields are modified by a multileaf collimator (MLC)? The presented analysis is capable of segmenting a MV field from the blocking MLC and detecting visible fiducials. This enables the calculation of nearly real-time 3D positions of markers during a real treatment. (4) Is the analysis fast enough to track fiducials in nearly real time? Multiple methods are adopted to predict marker positions and reduce search regions. The average detection time per frame for three markers in a 1024×768 image was reduced to 0.1 s or less. Solving these four issues paves the way to tracking moving fiducial markers throughout a 3DCRT or IMRT treatment. Altogether, these four studies demonstrate that our algorithm can track fiducials in real time, on degraded kV images (MV scatter), in rapidly moving tumors (fiducial blurring), and even provide useful information in the case when some fiducials are blocked from view by the MLC. This technique can provide a gating signal

  7. Distribution and role of Kv3.1b in neurons in the medial septum diagonal band complex.

    PubMed

    Henderson, Z; Lu, C B; Janzsó, G; Matto, N; McKinley, C E; Yanagawa, Y; Halasy, K

    2010-03-31

    The medial septum diagonal band complex (MS/DB) projects via cholinergic and GABAergic pathways to the hippocampus and plays a key role in the hippocampal theta rhythm. In the MS/DB we have previously described a population of fast spiking GABAergic neurons that contain parvalbumin and mediate theta frequency activity in vitro. The Kv3.1 potassium channel is a delayed rectifier channel that plays a major role in fast spiking neurons in the CNS, and has previously been localized in the MS/DB. To determine which cell types in the MS/DB express the Kv3.1b ion channel subunit, transgenic mice in which the expression of GABAergic and glutamate markers are associated with the expression of green fluorescent protein (GFP; GAD67-GFP and VGluT2-GFP mice, respectively) were used for immunofluorescence and axonal tract tracing. Electrophysiological studies were also carried out on rat MS/DB slices to examine the role of the Kv3.1 channel in theta frequency oscillations. The results for the MS/DB were as follows: (1) cholinergic cells did not express GFP in either GAD67-GFP or VGluT2-GFP mice, and there was GAD67 immunoreactivity in GFP-positive neurons in GAD67-GFP mice and in a small proportion (6%) of GFP-positive neurons in VGluT2-GFP mice. (2) Kv3.1b immunofluorescence was associated with the somata of GABAergic neurons, especially those that contained parvalbumin, and with a minority of glutamatergic neurons, but not with cholinergic neurons, and with GABAergic axonal terminal-like processes around certain GABAergic neurons. (3) Both Kv3.1b-positive and -negative GABAergic neurons were septo-hippocampal, and there was a minor projection to hippocampus from VGluT2-GFP neurons. (4) Kainate-induced theta oscillations in the MS/DB slice were potentiated rather than inhibited by the Kv3.1 blocker 4-aminopyridine, and this agent on its own produced theta frequency oscillations in MS/DB slices that were reduced by ionotropic glutamate and GABA receptor antagonists and abolished

  8. A fiducial detection algorithm for real-time image guided IMRT based on simultaneous MV and kV imaging.

    PubMed

    Mao, Weihua; Riaz, Nadeem; Lee, Louis; Wiersma, Rodney; Xing, Lei

    2008-08-01

    The advantage of highly conformal dose techniques such as 3DCRT and IMRT is limited by intrafraction organ motion. A new approach to gain near real-time 3D positions of internally implanted fiducial markers is to analyze simultaneous onboard kV beam and treatment MV beam images (from fluoroscopic or electronic portal image devices). Before we can use this real-time image guidance for clinical 3DCRT and IMRT treatments, four outstanding issues need to be addressed. (1) How will fiducial motion blur the image and hinder tracking fiducials? kV and MV images are acquired while the tumor is moving at various speeds. We find that a fiducial can be successfully detected at a maximum linear speed of 1.6 cm/s. (2) How does MV beam scattering affect kV imaging? We investigate this by varying MV field size and kV source to imager distance, and find that common treatment MV beams do not hinder fiducial detection in simultaneous kV images. (3) How can one detect fiducials on images from 3DCRT and IMRT treatment beams when the MV fields are modified by a multileaf collimator (MLC)? The presented analysis is capable of segmenting a MV field from the blocking MLC and detecting visible fiducials. This enables the calculation of nearly real-time 3D positions of markers during a real treatment. (4) Is the analysis fast enough to track fiducials in nearly real time? Multiple methods are adopted to predict marker positions and reduce search regions. The average detection time per frame for three markers in a 1024 x 768 image was reduced to 0.1 s or less. Solving these four issues paves the way to tracking moving fiducial markers throughout a 3DCRT or IMRT treatment. Altogether, these four studies demonstrate that our algorithm can track fiducials in real time, on degraded kV images (MV scatter), in rapidly moving tumors (fiducial blurring), and even provide useful information in the case when some fiducials are blocked from view by the MLC. This technique can provide a gating signal or

  9. A novel epileptic encephalopathy mutation in KCNB1 disrupts Kv2.1 ion selectivity, expression, and localization

    PubMed Central

    Thiffault, Isabelle; Speca, David J.; Austin, Daniel C.; Cobb, Melanie M.; Eum, Kenneth S.; Safina, Nicole P.; Grote, Lauren; Farrow, Emily G.; Miller, Neil; Soden, Sarah; Kingsmore, Stephen F.

    2015-01-01

    The epileptic encephalopathies are a group of highly heterogeneous genetic disorders. The majority of disease-causing mutations alter genes encoding voltage-gated ion channels, neurotransmitter receptors, or synaptic proteins. We have identified a novel de novo pathogenic K+ channel variant in an idiopathic epileptic encephalopathy family. Here, we report the effects of this mutation on channel function and heterologous expression in cell lines. We present a case report of infantile epileptic encephalopathy in a young girl, and trio-exome sequencing to determine the genetic etiology of her disorder. The patient was heterozygous for a de novo missense variant in the coding region of the KCNB1 gene, c.1133T>C. The variant encodes a V378A mutation in the α subunit of the Kv2.1 voltage-gated K+ channel, which is expressed at high levels in central neurons and is an important regulator of neuronal excitability. We found that expression of the V378A variant results in voltage-activated currents that are sensitive to the selective Kv2 channel blocker guangxitoxin-1E. These voltage-activated Kv2.1 V378A currents were nonselective among monovalent cations. Striking cell background–dependent differences in expression and subcellular localization of the V378A mutation were observed in heterologous cells. Further, coexpression of V378A subunits and wild-type Kv2.1 subunits reciprocally affects their respective trafficking characteristics. A recent study reported epileptic encephalopathy-linked missense variants that render Kv2.1 a tonically activated, nonselective cation channel that is not voltage activated. Our findings strengthen the correlation between mutations that result in loss of Kv2.1 ion selectivity and development of epileptic encephalopathy. However, the strong voltage sensitivity of currents from the V378A mutant indicates that the loss of voltage-sensitive gating seen in all other reported disease mutants is not required for an epileptic encephalopathy

  10. Theoretical investigation of the design and performance of a dual energy (kV and MV) radiotherapy imager

    SciTech Connect

    Liu, Langechuan; Antonuk, Larry E. El-Mohri, Youcef; Zhao, Qihua; Jiang, Hao

    2015-04-15

    Purpose: In modern radiotherapy treatment rooms, megavoltage (MV) portal imaging and kilovoltage (kV) cone-beam CT (CBCT) imaging are performed using various active matrix flat-panel imager (AMFPI) designs. To expand the clinical utility of MV and kV imaging, MV AMFPIs incorporating thick, segmented scintillators and, separately, kV imaging using a beam’s eye view geometry have been investigated by a number of groups. Motivated by these previous studies, it is of interest to explore to what extent it is possible to preserve the benefits of kV and MV imaging using a single AMFPI design, given the considerably different x ray energy spectra used for kV and MV imaging. In this paper, considerations for the design of such a dual energy imager are explored through examination of the performance of a variety of hypothetical AMFPIs based on x ray converters employing segmented scintillators. Methods: Contrast, noise, and contrast-to-noise ratio performances were characterized through simulation modeling of CBCT imaging, while modulation transfer function, Swank factor, and signal performance were characterized through simulation modeling of planar imaging. The simulations were based on a previously reported hybrid modeling technique (accounting for both radiation and optical effects), augmented through modeling of electronic additive noise. All designs employed BGO scintillator material with thicknesses ranging from 0.25 to 4 cm and element-to-element pitches ranging from 0.508 to 1.016 mm. A series of studies were performed under both kV and MV imaging conditions to determine the most advantageous imager configuration (involving front or rear x ray illumination and use of a mirror or black reflector), converter design (pitch and thickness), and operating mode (pitch-binning combination). Results: Under the assumptions of the present study, the most advantageous imager design was found to employ rear illumination of the converter in combination with a black reflector

  11. Torque feedback transmission

    SciTech Connect

    Whalen, B.L.

    1987-01-20

    This patent describes an infinitely variable transmission of inline configuration for interconnecting a primer mover with a load for clutch free operation in a range of speed including hydraulic neutral comprising: a. planetary gear train means having a ring gear, planetary gears supported by a planetary gear carrier, and a sun gear, the sun gear being connected mechanically to the load, output shaft means for joining the sun gear to the load; b. variable torque feedback means comprising (i) a variable displacement hydraulic motor whose rotor shaft is in line with the output shaft means and drivingly connected to the prime mover and the planetary gear carrier during the full range of operation of the transmission, and (ii) a fixed displacement hydraulic pump connected hydraulically to the motor, the rotor shaft of the pump being connected mechanically to the ring gear and being axially displaced from the output shaft means; c. means for adjusting the displacement volume within the hydraulic motor for controlling the torque feedback in the transmission to provide infinitely variable coupling between the prime mover and the load over the full range of the transmission including hydraulic neutral; d. a speed reducer between the primer mover and the motor rotor shaft and a speed multiplier between the sun gear and the load; and e. mechanical transmission assembly means between the speed multiplier and the load in line with the motor rotor shaft and the output shaft means for providing selection of drive, reverse, park, and neutral.

  12. Ultrahigh transmission optical nanofibers

    NASA Astrophysics Data System (ADS)

    Hoffman, J. E.; Ravets, S.; Grover, J. A.; Solano, P.; Kordell, P. R.; Wong-Campos, J. D.; Orozco, L. A.; Rolston, S. L.

    2014-06-01

    We present a procedure for reproducibly fabricating ultrahigh transmission optical nanofibers (530 nm diameter and 84 mm stretch) with single-mode transmissions of 99.95 ± 0.02%, which represents a loss from tapering of 2.6 × 10-5 dB/mm when normalized to the entire stretch. When controllably launching the next family of higher-order modes on a fiber with 195 mm stretch, we achieve a transmission of 97.8 ± 2.8%, which has a loss from tapering of 5.0 × 10-4 dB/mm when normalized to the entire stretch. Our pulling and transfer procedures allow us to fabricate optical nanofibers that transmit more than 400 mW in high vacuum conditions. These results, published as parameters in our previous work, present an improvement of two orders of magnitude less loss for the fundamental mode and an increase in transmission of more than 300% for higher-order modes, when following the protocols detailed in this paper. We extract from the transmission during the pull, the only reported spectrogram of a fundamental mode launch that does not include excitation to asymmetric modes; in stark contrast to a pull in which our cleaning protocol is not followed. These results depend critically on the pre-pull cleanliness and when properly following our pulling protocols are in excellent agreement with simulations.

  13. Variability of Potassium Channel Blockers in Mesobuthus eupeus Scorpion Venom with Focus on Kv1.1

    PubMed Central

    Kuzmenkov, Alexey I.; Vassilevski, Alexander A.; Kudryashova, Kseniya S.; Nekrasova, Oksana V.; Peigneur, Steve; Tytgat, Jan; Feofanov, Alexey V.; Kirpichnikov, Mikhail P.; Grishin, Eugene V.

    2015-01-01

    The lesser Asian scorpion Mesobuthus eupeus (Buthidae) is one of the most widely spread and dispersed species of the Mesobuthus genus, and its venom is actively studied. Nevertheless, a considerable amount of active compounds is still under-investigated due to the high complexity of this venom. Here, we report a comprehensive analysis of putative potassium channel toxins (KTxs) from the cDNA library of M. eupeus venom glands, and we compare the deduced KTx structures with peptides purified from the venom. For the transcriptome analysis, we used conventional tools as well as a search for structural motifs characteristic of scorpion venom components in the form of regular expressions. We found 59 candidate KTxs distributed in 30 subfamilies and presenting the cysteine-stabilized α/β and inhibitor cystine knot types of fold. M. eupeus venom was then separated to individual components by multistage chromatography. A facile fluorescent system based on the expression of the KcsA-Kv1.1 hybrid channels in Escherichia coli and utilization of a labeled scorpion toxin was elaborated and applied to follow Kv1.1 pore binding activity during venom separation. As a result, eight high affinity Kv1.1 channel blockers were identified, including five novel peptides, which extend the panel of potential pharmacologically important Kv1 ligands. Activity of the new peptides against rat Kv1.1 channel was confirmed (IC50 in the range of 1–780 nm) by the two-electrode voltage clamp technique using a standard Xenopus oocyte system. Our integrated approach is of general utility and efficiency to mine natural venoms for KTxs. PMID:25792741

  14. Targeting the voltage sensor of Kv7.2 voltage-gated K+ channels with a new gating-modifier

    PubMed Central

    Peretz, Asher; Pell, Liat; Gofman, Yana; Haitin, Yoni; Shamgar, Liora; Patrich, Eti; Kornilov, Polina; Gourgy-Hacohen, Orit; Ben-Tal, Nir; Attali, Bernard

    2010-01-01

    The pore and gate regions of voltage-gated cation channels have been often targeted with drugs acting as channel modulators. In contrast, the voltage-sensing domain (VSD) was practically not exploited for therapeutic purposes, although it is the target of various toxins. We recently designed unique diphenylamine carboxylates that are powerful Kv7.2 voltage-gated K+ channel openers or blockers. Here we show that a unique Kv7.2 channel opener, NH29, acts as a nontoxin gating modifier. NH29 increases Kv7.2 currents, thereby producing a hyperpolarizing shift of the activation curve and slowing both activation and deactivation kinetics. In neurons, the opener depresses evoked spike discharges. NH29 dampens hippocampal glutamate and GABA release, thereby inhibiting excitatory and inhibitory postsynaptic currents. Mutagenesis and modeling data suggest that in Kv7.2, NH29 docks to the external groove formed by the interface of helices S1, S2, and S4 in a way that stabilizes the interaction between two conserved charged residues in S2 and S4, known to interact electrostatically, in the open state of Kv channels. Results indicate that NH29 may operate via a voltage-sensor trapping mechanism similar to that suggested for scorpion and sea-anemone toxins. Reflecting the promiscuous nature of the VSD, NH29 is also a potent blocker of TRPV1 channels, a feature similar to that of tarantula toxins. Our data provide a structural framework for designing unique gating-modifiers targeted to the VSD of voltage-gated cation channels and used for the treatment of hyperexcitability disorders. PMID:20713704

  15. In vitro and intrathecal siRNA mediated KV1.1 knock-down in primary sensory neurons

    PubMed Central

    Baker, Mark D.; Chen, Ya-Chun; Shah, Syed U.; Okuse, Kenji

    2011-01-01

    KV1.1 is a Shaker homologue K+ channel that contributes to the juxta-paranodal membrane conductance in myelinated axons, and is blocked by fampridine (4-aminopyridine), used to treat the symptoms of multiple sclerosis. The present experiments investigate KV1.1 function in primary sensory neurons and A-fibres, and help define its characteristics as a drug-target using sequence specific small-interfering RNAs (siRNAs). siRNA (71 nM) was used to knock-down functional expression of KV1.1 in sensory neurons (> 25 μm in apparent diameter) in culture, and was also delivered intrathecally in vivo (9.3 μg). K+ channel knock-down in sensory neurons was found to make the voltage-threshold for action potential generation significantly more negative than in control (p = 0.02), led to the breakdown of accommodation and promoted spontaneous action potential firing. Exposure to dendrotoxin-K (DTX-K, 10–100 nM) also selectively abolished K+ currents at negative potentials and made voltage-threshold more negative, consistent with KV1.1 controlling excitability close to the nominal resting potential of the neuron cell body, near − 60 mV. Introduction of one working siRNA sequence into the intrathecal space in vivo was associated with a small increase in the amplitude of the depolarising after-potential in sacral spinal roots (p < 0.02), suggesting a reduction in the number of working K+ channels in internodal axon membrane. Our study provides evidence that KV1.1 contributes to the control of peripheral sensory nerve excitability, and suggests that its characteristics as a putative drug target can be assessed by siRNA transfection in primary sensory neurons in vitro and in vivo. PMID:21903165

  16. Contribution of the Kv3.1 potassium channel to high-frequency firing in mouse auditory neurones

    PubMed Central

    Wang, Lu-Yang; Gan, Li; Forsythe, Ian D; Kaczmarek, Leonard K

    1998-01-01

    Using a combination of patch-clamp, in situ hybridization and computer simulation techniques, we have analysed the contribution of potassium channels to the ability of a subset of mouse auditory neurones to fire at high frequencies.Voltage-clamp recordings from the principal neurones of the medial nucleus of the trapezoid body (MNTB) revealed a low-threshold dendrotoxin (DTX)-sensitive current (ILT) and a high-threshold DTX-insensitive current (IHT).IHT displayed rapid activation and deactivation kinetics, and was selectively blocked by a low concentration of tetraethylammonium (TEA; 1 mm).The physiological and pharmacological properties of IHT very closely matched those of the Shaw family potassium channel Kv3.1 stably expressed in a CHO cell line.An mRNA probe corresponding to the C-terminus of the Kv3.1 channel strongly labelled MNTB neurones, suggesting that this channel is expressed in these neurones.TEA did not alter the ability of MNTB neurones to follow stimulation up to 200 Hz, but specifically reduced their ability to follow higher frequency impulses.A computer simulation, using a model cell in which an outward current with the kinetics and voltage dependence of the Kv3.1 channel was incorporated, also confirmed that the Kv3.1- like current is essential for cells to respond to a sustained train of high-frequency stimuli.We conclude that in mouse MNTB neurones the Kv3.1 channel contributes to the ability of these cells to lock their firing to high-frequency inputs. PMID:9547392

  17. Combined kV and MV imaging for real-time tracking of implanted fiducial markers1

    PubMed Central

    Wiersma, R. D.; Mao, Weihua; Xing, L.

    2008-01-01

    In the presence of intrafraction organ motion, target localization uncertainty can greatly hamper the advantage of highly conformal dose techniques such as intensity modulated radiation therapy (IMRT). To minimize the adverse dosimetric effect caused by tumor motion, a real-time knowledge of the tumor position is required throughout the beam delivery process. The recent integration of onboard kV diagnostic imaging together with MV electronic portal imaging devices on linear accelerators can allow for real-time three-dimensional (3D) tumor position monitoring during a treatment delivery. The aim of this study is to demonstrate a near real-time 3D internal fiducial tracking system based on the combined use of kV and MV imaging. A commercially available radiotherapy system equipped with both kV and MV imaging systems was used in this work. A hardware video frame grabber was used to capture both kV and MV video streams simultaneously through independent video channels at 30 frames per second. The fiducial locations were extracted from the kV and MV images using a software tool. The geometric tracking capabilities of the system were evaluated using a pelvic phantom with embedded fiducials placed on a moveable stage. The maximum tracking speed of the kV∕MV system is approximately 9 Hz, which is primarily limited by the frame rate of the MV imager. The geometric accuracy of the system is found to be on the order of less than 1 mm in all three spatial dimensions. The technique requires minimal hardware modification and is potentially useful for image-guided radiation therapy systems. PMID:18491510

  18. Number of lightning discharges causing damage to lightning arrester cables for aerial transmission lines in power systems

    SciTech Connect

    Nikiforov, E. P.

    2009-07-15

    Damage by lightning discharges to lightning arrester cables for 110-175 kV aerial transmission lines is analyzed using data from power systems on incidents with aerial transmission lines over a ten year operating period (1997-2006). It is found that failures of lightning arrester cables occur when a tensile force acts on a cable heated to the melting point by a lightning current. The lightning currents required to heat a cable to this extent are greater for larger cable cross sections. The probability that a lightning discharge will develop decreases as the amplitude of the lightning current increases, which greatly reduces the number of lightning discharges which damage TK-70 cables compared to TK-50 cables. In order to increase the reliability of lightning arrester cables for 110 kV aerial transmission lines, TK-70 cables should be used in place of TK-50 cables. The number of lightning discharges per year which damage lightning arrester cables is lowered when the density of aerial transmission lines is reduced within the territory of electrical power systems. An approximate relationship between these two parameters is obtained.

  19. Automotive transmission linkage system

    SciTech Connect

    Yen, F.Y.; Ardayfio, D.D.

    1990-10-02

    This patent describes a system for converting a manual multi-speed transmission to operate as an automatic-manual transmission, the system being disposed within a vehicle, the transmission having a conventional gearshift lever and a clutch pedal. It comprises: a gearshift position selection panel, the panel being located apart from the gearshift lever, the panel enabling a driver to select the desired gear position of the gearshift lever by manipulating the panel without the necessity of the driver handling the gearshift lever; a controller which transforms the gearshift selection of the driver to an output signal, the signal corresponding to the gearshift position selected by the driver; and actuating means for mechanically repositioning the gearshift lever automatically in accordance with the output signal.

  20. Aerosol Transmission of Filoviruses

    PubMed Central

    Mekibib, Berhanu; Ariën, Kevin K.

    2016-01-01

    Filoviruses have become a worldwide public health concern because of their potential for introductions into non-endemic countries through international travel and the international transport of infected animals or animal products. Since it was first identified in 1976, in the Democratic Republic of Congo (formerly Zaire) and Sudan, the 2013–2015 western African Ebola virus disease (EVD) outbreak is the largest, both by number of cases and geographical extension, and deadliest, recorded so far in medical history. The source of ebolaviruses for human index case(s) in most outbreaks is presumptively associated with handling of bush meat or contact with fruit bats. Transmission among humans occurs easily when a person comes in contact with contaminated body fluids of patients, but our understanding of other transmission routes is still fragmentary. This review deals with the controversial issue of aerosol transmission of filoviruses. PMID:27223296