Contribution of kv7.4/kv7.5 heteromers to intrinsic and calcitonin gene-related Peptide-induced cerebral reactivity

DEFF Research Database (Denmark)

Chadha, Preet S; Jepps, Thomas A; Carr, Georgina

2014-01-01

Middle cerebral artery (MCA) diameter is regulated by inherent myogenic activity and the effect of potent vasodilators such as calcitonin gene-related peptide (CGRP). Previous studies showed that MCAs express KCNQ1, 4, and 5 potassium channel genes, and the expression products (Kv7 channels) part......) participate in the myogenic control of MCA diameter. The present study investigated the contribution of Kv7.4 and Kv7.5 isoforms to myogenic and CGRP regulation of MCA diameter and determined whether they were affected in hypertensive animals....

A novel homozygous AP4B1 mutation in two brothers with AP-4 deficiency syndrome and ocular anomalies.

Science.gov (United States)

Accogli, Andrea; Hamdan, Fadi F; Poulin, Chantal; Nassif, Christina; Rouleau, Guy A; Michaud, Jacques L; Srour, Myriam

2018-04-01

Adaptor protein complex-4 (AP-4) is a heterotetrameric protein complex which plays a key role in vesicle trafficking in neurons. Mutations in genes affecting different subunits of AP-4, including AP4B1, AP4E1, AP4S1, and AP4M1, have been recently associated with an autosomal recessive phenotype, consisting of spastic tetraplegia, and intellectual disability (ID). The overlapping clinical picture among individuals carrying mutations in any of these genes has prompted the terms "AP-4 deficiency syndrome" for this clinically recognizable phenotype. Using whole-exome sequencing, we identified a novel homozygous mutation (c.991C>T, p.Q331*, NM_006594.4) in AP4B1 in two siblings from a consanguineous Pakistani couple, who presented with severe ID, progressive spastic tetraplegia, epilepsy, and microcephaly. Sanger sequencing confirmed the mutation was homozygous in the siblings and heterozygous in the parents. Similar to previously reported individuals with AP4B1 mutations, brain MRI revealed ventriculomegaly and white matter loss. Interestingly, in addition to the typical facial gestalt reported in other AP-4 deficiency cases, the older brother presented with congenital left Horner syndrome, bilateral optic nerve atrophy and cataract, which have not been previously reported in this condition. In summary, we report a novel AP4B1 homozygous mutation in two siblings and review the phenotype of AP-4 deficiency, speculating on a possible role of AP-4 complex in eye development. © 2018 Wiley Periodicals, Inc.

Identification of a functional interaction between Kv4.3 channels and c-Src tyrosine kinase.

Science.gov (United States)

Gomes, Pedro; Saito, Tomoaki; Del Corsso, Cris; Alioua, Abderrahmane; Eghbali, Mansoureh; Toro, Ligia; Stefani, Enrico

2008-10-01

Voltage-gated K(+) (Kv) channels are key determinants of cardiac and neuronal excitability. A substantial body of evidence has accumulated in support of a role for Src family tyrosine kinases in the regulation of Kv channels. In this study, we examined the possibility that c-Src tyrosine kinase participates in the modulation of the transient voltage-dependent K(+) channel Kv4.3. Supporting a mechanistic link between Kv4.3 and c-Src, confocal microscopy analysis of HEK293 cells stably transfected with Kv4.3 showed high degree of co-localization of the two proteins at the plasma membrane. Our results further demonstrate an association between Kv4.3 and c-Src by co-immunoprecipitation and GST pull-down assays, this interaction being mediated by the SH2 and SH3 domains of c-Src. Furthermore, we show that Kv4.3 is tyrosine phosphorylated under basal conditions. The functional relevance of the observed interaction between Kv4.3 and c-Src was established in patch-clamp experiments, where application of the Src inhibitor PP2 caused a decrease in Kv4.3 peak current amplitude, but not the inactive structural analogue PP3. Conversely, intracellular application of recombinant c-Src kinase or the protein tyrosine phosphatase inhibitor bpV(phen) increased Kv4.3 peak current amplitude. In conclusion, our findings provide evidence that c-Src-induced Kv4.3 channel activation involves their association in a macromolecular complex and suggest a role for c-Src-Kv4.3 pathway in regulating cardiac and neuronal excitability.

Modification of the Charlesby law. Pt. 2. Macroscopic sensitivity

International Nuclear Information System (INIS)

Schiltz, A.; Weil, A.; Paniez, P.

1984-01-01

In part II, results are presented showing that for doses below macroscopic sensitivity, Qsub(sm), degradation due to fluence of the particles seems to be non-uniform over the entire area. In the light of this, a modification of the Charlesby's law is proposed providing a solution to the problems considered in part I [fr

Regulation of Kv1.4 potassium channels by PKC and AMPK kinases

DEFF Research Database (Denmark)

Andersen, Martin Nybo; Skibsbye, Lasse; Saljic, Arnela

2018-01-01

around the ubiquitin ligase Nedd4-2. In the present study we examined whether Kv1.4, constituting the cardiac Ito,s current, is subject to similar regulation. In the epithelial Madin-Darby Canine Kidney (MDCK) cell line, which constitutes a highly reproducible model system for addressing membrane...... targeting, we find, by confocal microscopy, that Kv1.4 cell surface expression is downregulated by activation of protein kinase C (PKC) and AMP-activated protein kinase (AMPK). In contrast, manipulating the activities of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and serum and glucocorticoid......-regulated kinase 1 (SGK1) were without effect on channel localization. The PKC and AMPK-mediated downregulation of Kv1.4 membrane surface localization was confirmed by two-electrode voltage clamp in Xenopus laevis oocytes, where pharmacological activation of PKC and AMPK reduced Kv1.4 current levels. We further...

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

International Nuclear Information System (INIS)

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

2009-01-01

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.

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

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Christina Gross

2016-09-01

Full Text Available 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.

Touch and step potential analysis at 23.9kV to 4.16kV & 13.8kV to 4.16kV distribution substations with pad-mounted transformers, floating grounds, and other exposed ungrounded metal bodies using WinIGS

Science.gov (United States)

Guzman, David G.

An electrical substation is composed of various subsystems that allow for the effective and safe operation of the power grid. One of the subsystems integrating a conventional substation is defined as the ground grid system. This system allows for the effective operation of the power grid and all the electrical equipment connected to it by providing a ground potential reference, commonly known as the system ground. In addition, the ground grid system provides safety to the workers and the public transiting inside or living nearby a substation by reducing the step and touch potential (or voltage) levels present during a system fault. In today's utility industry practices there is an increasing trend for using pad-mounted electrical equipment for substation applications in an effort to construct new or upgrade existing electrical facilities inside limited property spaces. This thesis work presents an analysis for the effects of touch and step voltages at existing distribution substations where 23.9kV to 4.16kV & 13.8kV to 4.16kV pad-mounted transformers and other pad-mounted switchgear was installed to replace the traditional station class equipment. Moreover, this study will expose modeling techniques employed to define and determine the effects of floating grounds and other exposed metal bodies inside or surrounding these substations using WinIGS; this is in an effort to determine any risks of electric shock associated with this type of installations. The results presented in this work are intended to verify the requirements for the ground grid analysis and design for 4.16kV distribution substations with pad-mounted equipment in order to prevent dangerous step and touch voltage levels appearing at these sites during system faults; and ultimately prevent exposing individuals to the risk of an electric shock.

Mechanosensitive gating of Kv channels.

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Catherine E Morris

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

KCNE3 is an inhibitory subunit of the Kv4.3 potassium channel

DEFF Research Database (Denmark)

Lundby, Alicia; Olesen, Søren-Peter

2006-01-01

The mammalian Kv4.3 potassium channel is a fast activating and inactivating K+ channel widely distributed in mammalian tissues. Kv4.3 is the major component of various physiologically important currents ranging from A-type currents in the CNS to the transient outward potassium conductance in the ...

A comparison of kV and MV imaging in head and neck image guided radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Devereux, B. [Radiation Oncology Queensland, 280 North St, Toowoomba 4350 (Australia)], E-mail: beth.devereux@roq.net.au; Frantzis, J.; Sisson, T.; Jones, M.; Martin, J.; Middleton, M. [Radiation Oncology Queensland, 280 North St, Toowoomba 4350 (Australia)

2010-02-15

Purpose: To compare and assess kV and MV imaging modalities and their role in image guided radiotherapy (IGRT) for head and neck cancer patients. Method: Twelve patients receiving radical radiotherapy to the head and neck were analysed in this study. Six patients undertook MV daily online intervention and a further six patients undertook kV daily online intervention. Pre-intervention field placement data were collected from three separate observers' image match analysis for each patient. The radiotherapy collective involved in the daily online image match analysis formed the fourth observer in the study. The primary end point was to establish the difference in inter- and intra-observer variance between kV and MV imaging modalities. Results: The range of the standard deviations of systematic set-up error for MV imaging calculated was 1.47-2.33 mm (MV) and 1.61-1.64 mm (kV) for the right-left (RL), 2.10-2.17 mm (MV) and 1.53-1.84 mm (kV) for the cranio-caudal (CC) and 1.43-1.63 mm (MV) and 1.02-1.11 mm (kV) for the anterior-posterior (AP). The mean inter-observer variance was 0.21 mm (MV) and 0.41 mm (kV) for the RL, 0.53 mm (MV) and 0.55 mm (kV) for the CC and 0.23 mm (MV) and 0.16 mm (kV) for the AP direction. Intra-observer mean variance was in the order of 0.60 mm (MV) and 0.16 mm (kV) for the RL, 1.41 mm (MV) and 0.05 mm (kV) for the CC and 1.41 mm (MV) and 0.08 mm (kV) for the AP. Discussion: The data in this study suggest both inter- and intra-observer consistency across kV and MV imaging modalities were comparable. However, it is felt that the improved clarity and quality of kV imaging allows all observers to analyse images in a consistent manner, identifying and acting on potential field placement moves. Conclusion: The introduction of kV imaging has maintained the high levels of inter- and intra-observer consistency achieved with MV imaging. This in turn further enables positive verification outcomes and supports the implementation of potential

L-Cysteine and L-AP4 microinjections in the rat caudal ventrolateral medulla decrease arterial blood pressure.

Science.gov (United States)

Takemoto, Yumi

2014-12-01

The thiol amino acid L-cysteine increases arterial blood pressure (ABP) when injected into the cerebrospinal fluid space in conscious rats, indicating a pressor response to centrally acting L-cysteine. A prior synaptic membrane binding assay suggests that L-cysteine has a strong affinity for the L-2-amino-4-phosphonobutyric acid (L-AP4) binding site. The central action of L-cysteine may be vial-AP4 sensitive receptors. The present study investigated cardiovascular responses to L-cysteine and L-ap4 microinjected into the autonomic area of the caudal ventrolateral medulla (CVLM) where inhibitory neurons regulate ABP via pre-sympathetic vasomotor neurons. Both the injection of L-cysteine and L-AP4 in the CVLM sites identified with L-glutamate produced the same depressor and bradycardic responses in urethane-anesthetized rats. Neither a prior antagonist microinjection of MK801 for the N-methyl-D-aspartate (NMDA) receptor nor CNQX for the non-NMDA receptor attenuated the responses to L-cysteine, but the combination of the two receptor blocking with an additional prior injection abolished the response. In contrast, either receptor blockade alone abolished the response to L-AP4, indicating distinct mechanisms between responses to L-cysteine and L-AP4 in the CVLM. The results indicate that the CVLM is a central active site for L-cysteine's cardiovascular response. Central L-cysteine's action could be independent of the L-AP4 sensitive receptors. Cardiovascular regulation may involve endogenous L-cysteine in the CVLM. Further multidisciplinary examinations are required to elaborate on L-cysteine's functional roles in the CVLM. Copyright © 2014 Elsevier B.V. All rights reserved.

KCNE4 is an inhibitory subunit to Kv1.1 and Kv1.3 potassium channels

DEFF Research Database (Denmark)

Grunnet, Morten; Rasmussen, Hannne B; Hay-Schmidt, Anders

2003-01-01

is detected in the heart and in five different parts of the brain. Having the broad distribution of Kv1 channels in mind, the demonstrated inhibitory property of KCNE4-subunits could locally and/or transiently have a dramatic influence on cellular excitability and on setting resting membrane potentials....

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

Science.gov (United States)

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.

MicroRNA-301a mediated regulation of Kv4.2 in diabetes: identification of key modulators.

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Siva K Panguluri

Full Text Available Diabetes is a metabolic disorder that ultimately results in major pathophysiological complications in the cardiovascular system. Diabetics are predisposed to higher incidences of sudden cardiac deaths (SCD. Several studies have associated diabetes as a major underlying risk for heart diseases and its complications. The diabetic heart undergoes remodeling to cope up with the underlying changes, however ultimately fails. In the present study we investigated the changes associated with a key ion channel and transcriptional factors in a diabetic heart model. In the mouse db/db model, we identified key transcriptional regulators and mediators that play important roles in the regulation of ion channel expression. Voltage-gated potassium channel (Kv4.2 is modulated in diabetes and is down regulated. We hypothesized that Kv4.2 expression is altered by potassium channel interacting protein-2 (KChIP2 which is regulated upstream by NFkB and miR-301a. We utilized qRT-PCR analysis and identified the genes that are affected in diabetes in a regional specific manner in the heart. At protein level we identified and validated differential expression of Kv4.2 and KChIP2 along with NFkB in both ventricles of diabetic hearts. In addition, we identified up-regulation of miR-301a in diabetic ventricles. We utilized loss and gain of function approaches to identify and validate the role of miR-301a in regulating Kv4.2. Based on in vivo and in vitro studies we conclude that miR-301a may be a central regulator for the expression of Kv4.2 in diabetes. This miR-301 mediated regulation of Kv4.2 is independent of NFkB and Irx5 and modulates Kv4.2 by direct binding on Kv4.2 3'untranslated region (3'-UTR. Therefore targeting miR-301a may offer new potential for developing therapeutic approaches.

β-Secretase BACE1 Promotes Surface Expression and Function of Kv3.4 at Hippocampal Mossy Fiber Synapses.

Science.gov (United States)

Hartmann, Stephanie; Zheng, Fang; Kyncl, Michele C; Karch, Sandra; Voelkl, Kerstin; Zott, Benedikt; D'Avanzo, Carla; Lomoio, Selene; Tesco, Giuseppina; Kim, Doo Y; Alzheimer, Christian; Huth, Tobias

2018-04-04

The β-secretase β-site APP-cleaving enzyme 1 (BACE1) is deemed a major culprit in Alzheimer's disease, but accumulating evidence indicates that there is more to the enzyme than driving the amyloidogenic processing of the amyloid precursor protein. For example, BACE1 has emerged as an important regulator of neuronal activity through proteolytic and, most unexpectedly, also through nonproteolytic interactions with several ion channels. Here, we identify and characterize the voltage-gated K + channel 3.4 (Kv3.4) as a new and functionally relevant interaction partner of BACE1. Kv3.4 gives rise to A-type current with fast activating and inactivating kinetics and serves to repolarize the presynaptic action potential. We found that BACE1 and Kv3.4 are highly enriched and remarkably colocalized in hippocampal mossy fibers (MFs). In BACE1 -/- mice of either sex, Kv3.4 surface expression was significantly reduced in the hippocampus and, in synaptic fractions thereof, Kv3.4 was specifically diminished, whereas protein levels of other presynaptic K + channels such as K Ca 1.1 and K Ca 2.3 remained unchanged. The apparent loss of presynaptic Kv3.4 affected the strength of excitatory transmission at the MF-CA3 synapse in hippocampal slices of BACE1 -/- mice when probed with the Kv3 channel blocker BDS-I. The effect of BACE1 on Kv3.4 expression and function should be bidirectional, as predicted from a heterologous expression system, in which BACE1 cotransfection produced a concomitant upregulation of Kv3.4 surface level and current based on a physical interaction between the two proteins. Our data show that, by targeting Kv3.4 to presynaptic sites, BACE1 endows the terminal with a powerful means to regulate the strength of transmitter release. SIGNIFICANCE STATEMENT The β-secretase β-site APP-cleaving enzyme 1 (BACE1) is infamous for its crucial role in the pathogenesis of Alzheimer's disease, but its physiological functions in the intact nervous system are only gradually

A limited 4 Å radial displacement of the S4-S5 linker is sufficient for internal gate closing in Kv channels.

Science.gov (United States)

Faure, Élise; Starek, Greg; McGuire, Hugo; Bernèche, Simon; Blunck, Rikard

2012-11-16

Voltage-gated ion channels are responsible for the generation of action potentials in our nervous system. Conformational rearrangements in their voltage sensor domains in response to changes of the membrane potential control pore opening and thus ion conduction. Crystal structures of the open channel in combination with a wealth of biophysical data and molecular dynamics simulations led to a consensus on the voltage sensor movement. However, the coupling between voltage sensor movement and pore opening, the electromechanical coupling, occurs at the cytosolic face of the channel, from where no structural information is available yet. In particular, the question how far the cytosolic pore gate has to close to prevent ion conduction remains controversial. In cells, spectroscopic methods are hindered because labeling of internal sites remains difficult, whereas liposomes or detergent solutions containing purified ion channels lack voltage control. Here, to overcome these problems, we controlled the state of the channel by varying the lipid environment. This way, we directly measured the position of the S4-S5 linker in both the open and the closed state of a prokaryotic Kv channel (KvAP) in a lipid environment using Lanthanide-based resonance energy transfer. We were able to reconstruct the movement of the covalent link between the voltage sensor and the pore domain and used this information as restraints for molecular dynamics simulations of the closed state structure. We found that a small decrease of the pore radius of about 3-4 Å is sufficient to prevent ion permeation through the pore.

S3b amino acid substitutions and ancillary subunits alter the affinity of Heteropoda venatoria toxin 2 for Kv4.3.

Science.gov (United States)

DeSimone, Christopher V; Lu, YiChun; Bondarenko, Vladimir E; Morales, Michael J

2009-07-01

Heteropoda venatoria toxin 2 (HpTx2) is an inhibitor cystine knot (ICK)-gating modifier toxin that selectively inhibits Kv4 channels. To characterize the molecular determinants of interaction, we performed alanine scanning of the Kv4.3 S3b region. HpTx2-Kv4.3 interaction had an apparent K(d) value of 2.3 microM. Two alanine mutants in Kv4.3 increased K(d) values to 6.4 microM for V276A and 25 microM for L275A. Simultaneous mutation of both amino acids to alanine nearly eliminated toxin interaction. Unlike Hanatoxin and other well characterized ICK toxins, HpTx2 binding does not require a charged amino acid for interaction. To determine whether the identity of the S3b binding site amino acids altered HpTx2 specificity, we constructed Kv4.3 [LV275IF]. This mutation decreased the K(d) value to 0.54 microM, suggesting that the hydrophobic character of the putative binding site is the most important property for interaction with HpTx2. One mutant, N280A, caused stronger interaction of HpTx2 with Kv4.3; the K(d) value for Kv4.3 [N280A] was 0.26 microM. To understand Kv4.3-based transient outward currents in native tissues, we tested the affinity of HpTx2 for Kv4.3 coexpressed with KChIP2b. The toxin's K(d) value for Kv4.3 + KChIP2b was 0.95 microM. KChIP2b stabilizes the closed state of Kv4.3, suggesting that the increased toxin affinity is due to increased stabilization of the closed state. These data show that HpTx2 binding to Kv4.3 has aspects in common with other ICK gating modifier toxins but that the interventions that increase toxin affinity suggest flexibility toward channel binding that belies its unusual specificity for Kv4 channels.

Kv4.2 knockout mice display learning and memory deficits in the Lashley maze [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Gregory D. Smith

2016-10-01

Full Text Available Background: Potassium channels have been shown to be involved in neural plasticity and learning. Kv4.2 is a subunit of the A-type potassium channel. Kv4.2 channels modulate excitability in the dendrites of pyramidal neurons in the cortex and hippocampus. Deletion of Kv4.2 results in spatial learning and conditioned fear deficits; however, previous studies have only examined deletion of Kv4.2 in aversive learning tests. Methods: For the current study, we used the Lashley maze as an appetitive learning test. We examined Kv4.2 wildtype (WT and knockout (KO mice in the Lashley maze over 4 days during adulthood. The first day consisted of habituating the mice to the maze. The mice then received five trials per day for the next 3 days. The number of errors and the time to the goal box was recorded for each trial. The goal box contained a weigh boat with an appetitive reward (gelatin with sugar. There was an intertrial interval of 15 minutes. Results: We found that Kv4.2 KO mice committed more errors across the trials compared to the WT mice p<0.001. There was no difference in the latency to find the goal box over the period. Discussion: Our finding that deletion of Kv4.2 resulted in more errors in the Lashley maze across 15 trials contribute to a growing body of evidence that Kv4.2 channels are significantly involved in learning and memory.

Kv4.2 knockout mice display learning and memory deficits in the Lashley maze [version 2; referees: 2 approved

Directory of Open Access Journals (Sweden)

Gregory D. Smith

2017-02-01

Full Text Available Background: Potassium channels have been shown to be involved in neural plasticity and learning. Kv4.2 is a subunit of the A-type potassium channel. Kv4.2 channels modulate excitability in the dendrites of pyramidal neurons in the cortex and hippocampus. Deletion of Kv4.2 results in spatial learning and conditioned fear deficits; however, previous studies have only examined deletion of Kv4.2 in aversive learning tests. Methods: For the current study, we used the Lashley maze as an appetitive learning test. We examined Kv4.2 wildtype (WT and knockout (KO mice in the Lashley maze over 4 days during adulthood. The first day consisted of habituating the mice to the maze. The mice then received five trials per day for the next 3 days. The number of errors and the time to the goal box was recorded for each trial. The goal box contained a weigh boat with an appetitive reward (gelatin with sugar. There was an intertrial interval of 15 minutes. Results: We found that Kv4.2 KO mice committed more errors across the trials compared to the WT mice p<0.001. There was no difference in the latency to find the goal box over the period. Discussion: Our finding that deletion of Kv4.2 resulted in more errors in the Lashley maze across 15 trials contribute to a growing body of evidence that Kv4.2 channels are significantly involved in learning and memory.

Power cables with extruded insulation and their accessories for rated voltages from 1 kV (Um = 1,2 kV) up to 30 kV (Um = 36 kV) : Part 2: cables for rated voltages from 6 kV (Um = 7,2 kV) up to 30 kV (Um = 36 kV)

CERN Document Server

International Electrotechnical Commission. Geneva

2005-01-01

Power cables with extruded insulation and their accessories for rated voltages from 1 kV (Um = 1,2 kV) up to 30 kV (Um = 36 kV) : Part 2: cables for rated voltages from 6 kV (Um = 7,2 kV) up to 30 kV (Um = 36 kV)

Contribution of delayed rectifier potassium currents to the electrical activity of murine colonic smooth muscle

Science.gov (United States)

Koh, S D; Ward, S M; Dick, G M; Epperson, A; Bonner, H P; Sanders, K M; Horowitz, B; Kenyon, J L

1999-01-01

We used intracellular microelectrodes to record the membrane potential (Vm) of intact murine colonic smooth muscle. Electrical activity consisted of spike complexes separated by quiescent periods (Vm≈−60 mV). The spike complexes consisted of about a dozen action potentials of approximately 30 mV amplitude. Tetraethylammonium (TEA, 1–10 mM) had little effect on the quiescent periods but increased the amplitude of the action potential spikes. 4-Aminopyridine (4-AP, ⋧ 5 mM) caused continuous spiking.Voltage clamp of isolated myocytes identified delayed rectifier K+ currents that activated rapidly (time to half-maximum current, 11.5 ms at 0 mV) and inactivated in two phases (τf = 96 ms, τs = 1.5 s at 0 mV). The half-activation voltage of the permeability was −27 mV, with significant activation at −50 mV.TEA (10 mM) reduced the outward current at potentials positive to 0 mV. 4-AP (5 mM) reduced the early current but increased outward current at later times (100–500 ms) consistent with block of resting channels relieved by depolarization. 4-AP inhibited outward current at potentials negative to −20 mV, potentials where TEA had no effect.Qualitative PCR amplification of mRNA identified transcripts encoding delayed rectifier K+ channel subunits Kv1.6, Kv4.1, Kv4.2, Kv4.3 and the Kvβ1.1 subunit in murine colon myocytes. mRNA encoding Kv 1.4 was not detected.We find that TEA-sensitive delayed rectifier currents are important determinants of action potential amplitude but not rhythmicity. Delayed rectifier currents sensitive to 4-AP are important determinants of rhythmicity but not action potential amplitude. PMID:10050014

Optically isolated, 2 kHz repetition rate, 4 kV solid-state pulse trigger generator.

Science.gov (United States)

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.

Decreased expression of Kv7 channels in Hirchsprung's disease.

Science.gov (United States)

O'Donnell, Anne-Marie; Coyle, David; Puri, Prem

2017-07-01

Voltage-dependent K + channels (Kv channels) participate in electrical rhythmicity and smooth muscle responses and are regulated by excitatory and inhibitory neurotransmitters. Kv channels also participate in the interstitial cell of Cajal (ICC) and smooth muscle cell (SMC) responses to neural inputs. The Kv family consists of 12 subfamilies, Kv1-Kv12, with five members of the Kv7 family identified to date: Kv7.1-Kv7.5. A recent study identified the potassium channel Kv7.5 as having a role in the excitability of ICC-IM in the mouse colon. We therefore designed this study to test the hypothesis that Kv7 channels are present in the normal human colon and are reduced in Hirschprung's disease (HSCR). HSCR tissue specimens were collected at the time of pull-through surgery (n=10), while normal control tissue specimens were obtained at the time of colostomy closure in patients with imperforate anus (n=10). Kv7.3-Kv7.5 immunohistochemistry was performed and visualized using confocal microscopy to assess their distribution. Western blot analysis was undertaken to determine Kv7.3-Kv7.5 protein quantification. Kv7.3 and Kv7.4-immunoreactivity was co-localized with neuron and ICC markers, while Kv7.5 was found to be expressed on both ICCs and SMCs. Western blot analysis revealed similar levels of Kv7.3 and Kv7.5 expression in the normal colon and HSCR colon, while Kv7.4 proteins were found to be markedly decreased in ganglionic specimens and decreased further in aganglionic specimens. A deficiency of Kv7.4 channels in the ganglionic and aganglionic bowel may place a role in colonic dysmotility in HSCR. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Science.gov (United States)

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.

Radiation effects on active pixel sensors (APS); Effets de l'irradiation sur les capteurs a pixels actifs (APS)

Energy Technology Data Exchange (ETDEWEB)

Cohen, M; David, J P [ONERA-CERT/, 31 - Toulouse (France)

1999-07-01

Active pixel sensor (APS) is a new generation of image sensors which presents several advantages relatively to charge coupled devices (CCDs) particularly for space applications (APS requires only 1 voltage to operate which reduces considerably current consumption). Irradiation was performed using {sup 60}Co gamma radiation at room temperature and at a dose rate of 150 Gy(Si)/h. 2 types of APS have been tested: photodiode-APS and photoMOS-APS. The results show that photoMOS-APS is more sensitive to radiation effects than photodiode-APS. Important parameters of image sensors like dark currents increase sharply with dose levels. Nevertheless photodiode-APS sensitivity is one hundred time lower than photoMOS-APS sensitivity.

Kv1 channels and neural processing in vestibular calyx afferents

Directory of Open Access Journals (Sweden)

Frances L Meredith

2015-06-01

Full Text Available 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.

Kv1 channels and neural processing in vestibular calyx afferents.

Science.gov (United States)

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.

Adrenergic Stress Protection of Human iPS Cell-Derived Cardiomyocytes by Fast Kv7.1 Recycling

Directory of Open Access Journals (Sweden)

Ilaria Piccini

2017-09-01

Full Text Available The fight-or-flight response (FFR, a physiological acute stress reaction, involves positive chronotropic and inotropic effects on heart muscle cells mediated through β-adrenoceptor activation. Increased systolic calcium is required to enable stronger heart contractions whereas elevated potassium currents are to limit the duration of the action potentials and prevent arrhythmia. The latter effect is accomplished by an increased functional activity of the Kv7.1 channel encoded by KCNQ1. Current knowledge, however, does not sufficiently explain the full extent of rapid Kv7.1 activation and may hence be incomplete. Using inducible genetic KCNQ1 complementation in KCNQ1-deficient human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs, we here reinvestigate the functional role of Kv7.1 in adapting human CMs to adrenergic stress. Under baseline conditions, Kv7.1 was barely detectable at the plasma membrane of hiPSC-CMs, yet it fully protected these from adrenergic stress-induced beat-to-beat variability of repolarization and torsade des pointes-like arrhythmia. Furthermore, isoprenaline treatment increased field potential durations specifically in KCNQ1-deficient CMs to cause these adverse macroscopic effects. Mechanistically, we find that the protective action by Kv7.1 resides in a rapid translocation of channel proteins from intracellular stores to the plasma membrane, induced by adrenergic signaling. Gene silencing experiments targeting RAB GTPases, mediators of intracellular vesicle trafficking, showed that fast Kv7.1 recycling under acute stress conditions is RAB4A-dependent.Our data reveal a key mechanism underlying the rapid adaptation of human cardiomyocytes to adrenergic stress. These findings moreover aid to the understanding of disease pathology in long QT syndrome and bear important implications for safety pharmacological screening.

Radiation effects on active pixel sensors (APS)

International Nuclear Information System (INIS)

Cohen, M.; David, J.P.

1999-01-01

Active pixel sensor (APS) is a new generation of image sensors which presents several advantages relatively to charge coupled devices (CCDs) particularly for space applications (APS requires only 1 voltage to operate which reduces considerably current consumption). Irradiation was performed using 60 Co gamma radiation at room temperature and at a dose rate of 150 Gy(Si)/h. 2 types of APS have been tested: photodiode-APS and photoMOS-APS. The results show that photoMOS-APS is more sensitive to radiation effects than photodiode-APS. Important parameters of image sensors like dark currents increase sharply with dose levels. Nevertheless photodiode-APS sensitivity is one hundred time lower than photoMOS-APS sensitivity

Radiation effects on active pixel sensors (APS); Effets de l'irradiation sur les capteurs a pixels actifs (APS)

Energy Technology Data Exchange (ETDEWEB)

Cohen, M.; David, J.P. [ONERA-CERT/, 31 - Toulouse (France)

1999-07-01

Active pixel sensor (APS) is a new generation of image sensors which presents several advantages relatively to charge coupled devices (CCDs) particularly for space applications (APS requires only 1 voltage to operate which reduces considerably current consumption). Irradiation was performed using {sup 60}Co gamma radiation at room temperature and at a dose rate of 150 Gy(Si)/h. 2 types of APS have been tested: photodiode-APS and photoMOS-APS. The results show that photoMOS-APS is more sensitive to radiation effects than photodiode-APS. Important parameters of image sensors like dark currents increase sharply with dose levels. Nevertheless photodiode-APS sensitivity is one hundred time lower than photoMOS-APS sensitivity.

Online Kidney Position Verification Using Non-Contrast Radiographs on a Linear Accelerator with on Board KV X-Ray Imaging Capability

International Nuclear Information System (INIS)

Willis, David J.; Kron, Tomas; Hubbard, Patricia; Haworth, Annette; Wheeler, Greg; Duchesne, Gillian M.

2009-01-01

The kidneys are dose-limiting organs in abdominal radiotherapy. Kilovoltage (kV) radiographs can be acquired using on-board imager (OBI)-equipped linear accelerators with better soft tissue contrast and lower radiation doses than conventional portal imaging. A feasibility study was conducted to test the suitability of anterior-posterior (AP) non-contrast kV radiographs acquired at treatment time for online kidney position verification. Anthropomorphic phantoms were used to evaluate image quality and radiation dose. Institutional Review Board approval was given for a pilot study that enrolled 5 adults and 5 children. Customized digitally reconstructed radiographs (DRRs) were generated to provide a priori information on kidney shape and position. Radiotherapy treatment staff performed online evaluation of kidney visibility on OBI radiographs. Kidney dose measured in a pediatric anthropomorphic phantom was 0.1 cGy for kV imaging and 1.7 cGy for MV imaging. Kidneys were rated as well visualized in 60% of patients (90% confidence interval, 34-81%). The likelihood of visualization appears to be influenced by the relative AP separation of the abdomen and kidneys, the axial profile of the kidneys, and their relative contrast with surrounding structures. Online verification of kidney position using AP non-contrast kV radiographs on an OBI-equipped linear accelerator appears feasible for patients with suitable abdominal anatomy. Kidney position information provided is limited to 2-dimensional 'snapshots,' but this is adequate in some clinical situations and potentially advantageous in respiratory-correlated treatments. Successful clinical implementation requires customized partial DRRs, appropriate imaging parameters, and credentialing of treatment staff.

Short-Circuit Characterization of 10 kV 10A 4H-SiC MOSFET

DEFF Research Database (Denmark)

Eni, Emanuel-Petre; Beczkowski, Szymon; Munk-Nielsen, Stig

2016-01-01

The short-circuit capability of a power device is highly relevant for converter design and fault protection. In this paper a 10kV 10A 4H-SiC MOSFET is characterized and its short circuit withstand capability is studied and analyzed at 6 kV DC-link voltage. The test setup for this study is also...... introduced as its design, especially the inductance in the switching loop, can affect the experimental results. The study aims to present insights specific to the device which are different from that of silicon (Si) based devices. During the short-circuit operation, MOSFET saturation current, ID...

Experimental study of 99Tcm-Ap4A in detection of atherosclerotic plaques

International Nuclear Information System (INIS)

Cao Wei; Zhang Yongxue; An Rui

2001-01-01

Objective: To study 99 Tc m labelled di-adenosine tetraphosphate (Ap4A), a compound can bind on P 2 purine receptors on atherosclerotic lesions, for imaging experimental atherosclerotic plaques in New Zealand White (NZW) rabbits. Methods: Twenty male NZW rabbits were submitted immune-injury and fed with high cholesterol diet for more than 2 months. To label the 99 Tc m to Ap4A, stannous tartrate solution was used. 99 Tc m -Ap4A was purified on a Sephadex G-25 column and tested for radiochemistry purity on thin layer chromatography. A biodistribution study was carried out on KM mice. Thirty minutes after intravenous injection of 7.4 MBq 99 Tc m -Ap4A, 5 normal NZW rabbits and 5 NZW rabbits with atherosclerotic lesions were sacrificed; their abdominal aortas were removed and covered with X-ray films. Exposed for 24 h in refrigerator, the films were developed and fixed. In another 5 NZW rabbits with atherosclerotic lesions, blood samples, atherosclerotic plaques and normal aortic wall samples were removed. Lesion to blood (target/blood, T/B), lesion to normal (target/non-target, T/NT) radioactivity ratios were calculated. 74 MBq 99 Tc m -Ap4A was injected into marginal ear veins of 5 atherosclerotic and 5 normal NZW rabbits. Simultaneously in vivo images were recorded for more than 4 h. In another group, 30 min after 99 Tc m -Ap4A administration, the animals were sacrificed and their abdominal aortas were removed. The abdominal aortas were placed on the face of SPECT and images acquisition was performed. Results: The radiochemistry purity of 99 Tc m -Ap4A was 85% to 91%. Biodistribution study revealed the clearance of 99 Tc m -Ap4A from blood was rapid. Thirty min after 99 Tc m -Ap4A administration, T/B radio was 3.17 +- 1.27, T/NT ratio was 5.23 +- 1.87. On the radioautography film shadows of atherosclerotic plaques were clearly visible. The atherosclerotic plaques on the aorta samples also can be seen on ex vivo images. Atherosclerotic abdominal aortas and lesions

Oxygen-Sensitive K+ Channels Modulate Human Chorionic Gonadotropin Secretion from Human Placental Trophoblast

Science.gov (United States)

Díaz, Paula; Sibley, Colin P.; Greenwood, Susan L.

2016-01-01

Human chorionic gonadotropin (hCG) is a key autocrine/paracrine regulator of placental syncytiotrophoblast, the transport epithelium of the human placenta. Syncytiotrophoblast hCG secretion is modulated by the partial pressure of oxygen (pO2), reactive oxygen species (ROS) and potassium (K+) channels. Here we test the hypothesis that K+ channels mediate the effects of pO2 and ROS on hCG secretion. Placental villous explants from normal term pregnancies were cultured for 6 days at 6% (normoxia), 21% (hyperoxia) or 1% (hypoxia) pO2. On days 3–5, explants were treated with 5mM 4-aminopyridine (4-AP) or tetraethylammonium (TEA), blockers of pO2-sensitive voltage-gated K+ (KV) channels, or ROS (10–1000μM H2O2). hCG secretion and lactate dehydrogenase (LDH) release, a marker of necrosis, were determined daily. At day 6, hCG and LDH were measured in tissue lysate and 86Rb (K+) efflux assessed to estimate syncytiotrophoblast K+ permeability. hCG secretion and 86Rb efflux were significantly greater in explants maintained in 21% pO2 than normoxia. 4-AP/TEA inhibited hCG secretion to a greater extent at 21% than 6% and 1% pO2, and reduced 86Rb efflux at 21% but not 6% pO2. LDH release and tissue LDH/hCG were similar in 6%, 21% and 1% pO2 and unaffected by 4-AP/TEA. H2O2 stimulated 86Rb efflux and hCG secretion at normoxia but decreased 86Rb efflux, without affecting hCG secretion, at 21% pO2. 4-AP/TEA-sensitive K+ channels participate in pO2-sensitive hCG secretion from syncytiotrophoblast. ROS effects on both hCG secretion and 86Rb efflux are pO2-dependent but causal links between the two remain to be established. PMID:26863525

Downregulation of Kv7.4 channel activity in primary and secondary hypertension

DEFF Research Database (Denmark)

Jepps, Thomas Andrew; Chadha, Preet S; Davis, Alison J

2011-01-01

Voltage-gated potassium (K(+)) channels encoded by KCNQ genes (Kv7 channels) have been identified in various rodent and human blood vessels as key regulators of vascular tone; however, nothing is known about the functional impact of these channels in vascular disease. We ascertained the effect of...... structurally different activators of Kv7.2 through Kv7.5 channels (BMS-204352, S-1, and retigabine) on blood vessels from normotensive and hypertensive animals.......Voltage-gated potassium (K(+)) channels encoded by KCNQ genes (Kv7 channels) have been identified in various rodent and human blood vessels as key regulators of vascular tone; however, nothing is known about the functional impact of these channels in vascular disease. We ascertained the effect of 3...

APETx4, a Novel Sea Anemone Toxin and a Modulator of the Cancer-Relevant Potassium Channel KV10.1

Directory of Open Access Journals (Sweden)

Lien Moreels

2017-09-01

Full Text Available The human ether-à-go-go channel (hEag1 or KV10.1 is a cancer-relevant voltage-gated potassium channel that is overexpressed in a majority of human tumors. Peptides that are able to selectively inhibit this channel can be lead compounds in the search for new anticancer drugs. Here, we report the activity-guided purification and electrophysiological characterization of a novel KV10.1 inhibitor from the sea anemone Anthopleura elegantissima. Purified sea anemone fractions were screened for inhibitory activity on KV10.1 by measuring whole-cell currents as expressed in Xenopus laevis oocytes using the two-microelectrode voltage clamp technique. Fractions that showed activity on Kv10.1 were further purified by RP-HPLC. The amino acid sequence of the peptide was determined by a combination of MALDI- LIFT-TOF/TOF MS/MS and CID-ESI-FT-ICR MS/MS and showed a high similarity with APETx1 and APETx3 and was therefore named APETx4. Subsequently, the peptide was electrophysiologically characterized on KV10.1. The selectivity of the toxin was investigated on an array of voltage-gated ion channels, including the cardiac human ether-à-go-go-related gene potassium channel (hERG or Kv11.1. The toxin inhibits KV10.1 with an IC50 value of 1.1 μM. In the presence of a similar toxin concentration, a shift of the activation curve towards more positive potentials was observed. Similar to the effect of the gating modifier toxin APETx1 on hERG, the inhibition of Kv10.1 by the isolated toxin is reduced at more positive voltages and the peptide seems to keep the channel in a closed state. Although the peptide also induces inhibitory effects on other KV and NaV channels, it exhibits no significant effect on hERG. Moreover, APETx4 induces a concentration-dependent cytotoxic and proapoptotic effect in various cancerous and noncancerous cell lines. This newly identified KV10.1 inhibitor can be used as a tool to further characterize the oncogenic channel KV10.1 or as a

Energetics and dynamics of the non-natural fluorescent 4AP:DAP base pair

KAUST Repository

Chawla, Mohit

2018-01-02

The fluorescent non-natural 4-aminophthalimide (4AP) base, when paired to the complementary 2,4-diaminopyrimidine (DAP) nucleobase, is accommodated in a B-DNA duplex being efficiently recognized and incorporated by DNA polymerases. To complement the experimental studies and rationalize the impact of the above non-natural bases on the structure, stability and dynamics of nucleic acid structures, we performed quantum mechanics (QM) calculations along with classical molecular dynamics (MD) simulations. QM calculations were initially focused on the geometry and energetics of the 4AP:DAP non-natural pair and of H-bonded base pairs between 4AP and all the natural bases in their classical Watson-Crick geometries. The QM calculations indicate that the 4AP:DAP pair, despite the fact that it can form 3 H-bonds in a classic Watson-Crick geometry, has a stability comparable to the A:T pair. Then, we extended the study to reverse Watson-Crick geometries, characteristic of parallel strands. MD simulations were carried out on two 13-mer DNA duplexes, featuring a central 4AP:DAP or A:T pair, respectively. No major structural deformation of the duplex was observed during the MD simulation. Snapshots from the MD simulations were subjected to QM calculations to investigate the 4AP:DAP interaction energy when embedded into a duplex structure, and to investigate the impact of the two non-natural bases on the stacking interactions with adjacent bases in the DNA duplex. We found a slight increase in stacking interactions involving the 4AP:DAP pair, counterbalanced by a moderate decrease in H-bonding interactions of the 4AP:DAP and of the adjacent base pairs in the duplex. The results of our study are in agreement with experimental data and complement them by providing an insight into which factors contribute positively and which factors contribute negatively to the structural compatibility of the fluorescent 4AP:DAP pair with a B-DNA structure.

High-resolution orientation and depth of insertion of the voltage-sensing S4 helix of a potassium channel in lipid bilayers.

Science.gov (United States)

Doherty, Tim; Su, Yongchao; Hong, Mei

2010-08-27

The opening and closing of voltage-gated potassium (Kv) channels are controlled by several conserved Arg residues in the S4 helix of the voltage-sensing domain. The interaction of these positively charged Arg residues with the lipid membrane has been of intense interest for understanding how membrane proteins fold to allow charged residues to insert into lipid bilayers against free-energy barriers. Using solid-state NMR, we have now determined the orientation and insertion depth of the S4 peptide of the KvAP channel in lipid bilayers. Two-dimensional (15)N correlation experiments of macroscopically oriented S4 peptide in phospholipid bilayers revealed a tilt angle of 40 degrees and two possible rotation angles differing by 180 degrees around the helix axis. Remarkably, the tilt angle and one of the two rotation angles are identical to those of the S4 helix in the intact voltage-sensing domain, suggesting that interactions between the S4 segment and other helices of the voltage-sensing domain are not essential for the membrane topology of the S4 helix. (13)C-(31)P distances between the S4 backbone and the lipid (31)P indicate a approximately 9 A local thinning and 2 A average thinning of the DMPC (1,2-dimyristoyl-sn-glycero-3-phosphochloline)/DMPG (1,2-dimyristoyl-sn-glycero-3-phosphatidylglycerol) bilayer, consistent with neutron diffraction data. Moreover, a short distance of 4.6 A from the guanidinium C(zeta) of the second Arg to (31)P indicates the existence of guanidinium phosphate hydrogen bonding and salt bridges. These data suggest that the structure of the Kv gating helix is mainly determined by protein-lipid interactions instead of interhelical protein-protein interactions, and the S4 amino acid sequence encodes sufficient information for the membrane topology of this crucial gating helix. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Low voltage 80 KV to 125 KV electron processors

International Nuclear Information System (INIS)

Lauppi, U.V.

1999-01-01

The classic electron beam technology made use of accelerating energies in the voltage range of 300 to 800 kV. The first EB processors - built for the curing of coatings - operated at 300 kV. The products to be treated were thicker than a simple layer of coating with thicknesses up to 100g and more. It was only in the beginning of the 1970's that industrial EB processors with accelerating voltages below 300 kV appeared on the market. Our company developed the first commercial electron accelerator without a beam scanner. The new EB machine featured a linear cathode, emitting a shower or 'curtain' of electrons over the full width of the product. These units were much smaller than anv previous EB processors and dedicated to the curing of coatings and other thin layers. ESI's first EB units operated with accelerating voltages between 150 and 200 kV. In 1993 ESI announced the introduction of a new generation of Electrocure. EB processors operating at 120 kV, and in 1998, at the RadTech North America '98 Conference in Chicago, the introduction of an 80 kV electron beam processor under the designation Microbeam LV

Dynamical fusion thresholds in macroscopic and microscopic theories

International Nuclear Information System (INIS)

Davies, K.T.R.; Sierk, A.J.; Nix, J.R.

1983-01-01

Macroscopic and microscopic results demonstrating the existence of dynamical fusion thresholds are presented. For macroscopic theories, it is shown that the extra-push dynamics is sensitive to some details of the models used, e.g. the shape parametrization and the type of viscosity. The dependence of the effect upon the charge and angular momentum of the system is also studied. Calculated macroscopic results for mass-symmetric systems are compared to experimental mass-asymmetric results by use of a tentative scaling procedure, which takes into account both the entrance-channel and the saddle-point regions of configuration space. Two types of dynamical fusion thresholds occur in TDHF studies: (1) the microscopic analogue of the macroscopic extra push threshold, and (2) the relatively high energy at which the TDHF angular momentum window opens. Both of these microscopic thresholds are found to be very sensitive to the choice of the effective two-body interaction

Novel Kv7.1-phosphatidylinositol 4,5-bisphosphate interaction sites uncovered by charge neutralization scanning

DEFF Research Database (Denmark)

Eckey, Karina; Wrobel, Eva; Strutz-Seebohm, Nathalie

2014-01-01

Kv7.1 to Kv7.5 α-subunits belong to the family of voltage-gated potassium channels (Kv). Assembled with the β-subunit KCNE1, Kv7.1 conducts the slowly activating potassium current IKs, which is one of the major currents underlying repolarization of the cardiac action potential. A known regulator...... of corresponding long QT syndrome mutants suggested impaired PIP2 regulation as the cause for channel dysfunction. To clarify the underlying structural mechanism of PIP2 binding, molecular dynamics simulations of Kv7.1/KCNE1 complexes containing two PIP2 molecules in each subunit at specific sites were performed...

Synthesis of diadenosine 5', 5'''-P1, P4-tetraphosphate (AP4A) in sea urchin embryos

International Nuclear Information System (INIS)

Morioka, Mizue; Shimada, Hiraku

1984-01-01

Sea urchin embryos were labeled with ( 3 H)adenosine at two developmental stages (morula and prism) and the labeled acid-soluble nucleotides were fractionated successively by column chromatography with DEAE-Sephadex and DEAE-cellulose, and by thin-layer chromatography on a PEI-cellulose plate. Significant radioactivity was detected on the PEI-cellulose plate at the region of diadenosine 5', 5'''-P 1 , P 4 -tetraphosphate (AP 4 A). After treatment of this fraction with phosphodiesterase, the radioactivity was all recovered in the AMP region, while alkaline phosphatase had no effect on the AP 4 A fraction. The present result suggests that AP 4 A is actively synthesized in the sea urchin embryos. (author)

AP4M1 is abnormally expressed in oxygen-glucose deprived hippocampal neurons.

Science.gov (United States)

Zhang, J; Cheng, X Y; Sheng, G Y

2014-03-20

AP4M1 mutations have been suggested to be associated with autosomal recessive cerebral palsy syndrome. But the pathogenic mechanism remains uncertain. The purpose of this study is to investigate whether and how AP4M1 expression is changed in injured neurons. Primary cultured hippocampal neurons were prepared for this experiment. They were subjected to oxygen-glucose deprivation (OGD) leading to apoptosis, mimicking brain ischemia. Neuron-specific enolase (NSE) was labeled immunofluorescently to confirm that the purity of neuron was higher than 90%. Real-time PCR and western blotting were performed to measure the gene expression. AP4M1 was labeled with MAP2 or Tau-1 to observe the distribution. We found that the AP4M1 protein levels immediately after the procedure were similar between the OGD group and the sham group. However, down-regulation was observed 12h after the reperfusion, and became more notable at 24h. The real-time PCR showed similar results, except that the down-regulation of mRNA was able to be detected immediately after the OGD. Immunofluorescent labeling revealed AP4M1 distributed in the dendrites of normal neurons, but it redistributed to the axons after the OGD procedure. In conclusion, AP4M1 is not only down-regulated at both the mRNA and protein levels, but also redistributed from dendrites to axons in oxygen-glucose deprived hippocampal neurons. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Information and self-organization a macroscopic approach to complex systems

CERN Document Server

Haken, Hermann

1988-01-01

Complex systems are ubiquitous, and practically all branches of science ranging from physics through chemistry and biology to economics and sociology have to deal with them. In this book we wish to present concepts and methods for dealing with complex systems from a unifying point of view. Therefore it may be of inter­ est to graduate students, professors and research workers who are concerned with theoretical work in the above-mentioned fields. The basic idea for our unified ap­ proach sterns from that of synergetics. In order to find unifying principles we shall focus our attention on those situations where a complex system changes its macroscopic behavior qualitatively, or in other words, where it changes its macroscopic spatial, temporal or functional structure. Until now, the theory of synergetics has usually begun with a microscopic or mesoscopic description of a complex system. In this book we present an approach which starts out from macroscopic data. In particular we shall treat systems that acquir...

Highly sensitive and simultaneous electrochemical determination of 2-aminophenol and 4-aminophenol based on poly(l-arginine)-β-cyclodextrin/carbon nanotubes@graphene nanoribbons modified electrode.

Science.gov (United States)

Yi, Yinhui; Zhu, Gangbing; Wu, Xiangyang; Wang, Kun

2016-03-15

Owing to the similar characteristics and physiochemical property of 2-aminophenol (2-AP) and 4-aminophenol (4-AP), the highly sensitive simultaneous electrochemical determination of 2- and 4-AP is a great challenge. In this paper, by electropolymerizing β-cyclodextrin (β-CD) and l-arginine (l-Arg) on the surface of carbon nanotubes@graphene nanoribbons (CNTs@GNRs) core-shell heterostructure, a P-β-CD-l-Arg/CNTs@GNRs nanohybrid modified electrode was prepared successfully, and it could exhibit the synergetic effects of β-CD (high host-guest recognition and enrichment ability), l-Arg (excellent electrocatalytic activity) and CNTs@GNRs (prominent electrochemical properties and large surface area), the P-β-CD-l-Arg/CNTs@GNRs modified electrode was used in the electrochemical determination of 2- and 4-AP, the results demonstrated that the highly sensitive and simultaneous determination of 2- and 4-AP is successfully achieved and the modified electrode has a linear response range of 25.0-1300.0 nM for both 2- and 4-AP, and the detection limits of 2- and 4-AP obtained in this work are 6.2 and 3.5 nM, respectively. Copyright © 2015 Elsevier B.V. All rights reserved.

Spatial distributions of Kv4 channels and KChip2 isoforms in the murine heart based on laser capture microdissection.

Science.gov (United States)

Teutsch, Christine; Kondo, Richard P; Dederko, Dorothy A; Chrast, Jacqueline; Chien, Kenneth R; Giles, Wayne R

2007-03-01

Regional differences in repolarizing K(+) current densities and expression levels of their molecular components are important for coordinating the pattern of electrical excitation and repolarization of the heart. The small size of hearts from mice may obscure these interventricular and/or transmural expression differences of K(+) channels. We have examined this possibility in adult mouse ventricle using a technology that provides very high spatial resolution of tissue collection. Conventional manual dissection and laser capture microdissection (LCM) were utilized to dissect tissue from distinct ventricular regions. RNA was isolated from epicardial, mid-myocardial and endocardial layers of both the right and left ventricles. Real-time RT-PCR was used to quantify the transcript expression in these different regions. LCM revealed significant interventricular and transmural gradients for both Kv4.2 and the alpha-subunit of KChIP2. The expression profile of a second K(+) channel transcript, Kir2.1, which is responsible for the inwardly rectifying K(+) current I(k1), showed no interventricular or transmural gradients and therefore served as a negative control. Our findings are in contrast to previous reports of a relatively uniform left ventricular transmural pattern of expression of Kv4.2, Kv4.3 and KChIP2 in adult mouse heart, which appear to be different than that in larger mammals. Specifically, our results demonstrate significant epi- to endocardial differences in the patterns of expression of both Kv4.2 and KChIP2.

Inactivation as a new regulatory mechanism for neuronal Kv7 channels

DEFF Research Database (Denmark)

Jensen, Henrik Sindal; Grunnet, Morten; Olesen, Søren-Peter

2007-01-01

neuronal channels and are important for controlling excitability. Kv7.1 channels have been considered the only Kv7 channels to undergo inactivation upon depolarization. However, here we demonstrate that inactivation is also an intrinsic property of Kv7.4 and Kv7.5 channels, which inactivate to a larger...

The importance of immunohistochemical analyses in evaluating the phenotype of Kv channel knockout mice.

Science.gov (United States)

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

2012-06-01

To gain insights into the phenotype of voltage-gated potassium (Kv)1.1 and Kv4.2 knockout mice, we used immunohistochemistry to analyze the expression of component principal or α subunits and auxiliary subunits of neuronal Kv channels in knockout mouse brains. Genetic ablation of the Kv1.1 α subunit did not result in compensatory changes in the expression levels or subcellular distribution of related ion channel subunits in hippocampal medial perforant path and mossy fiber nerve terminals, where high levels of Kv1.1 are normally expressed. Genetic ablation of the Kv4.2 α subunit did not result in altered neuronal cytoarchitecture of the hippocampus. Although Kv4.2 knockout mice did not exhibit compensatory changes in the expression levels or subcellular distribution of the related Kv4.3 α subunit, we found dramatic decreases in the cellular and subcellular expression of specific Kv channel interacting proteins (KChIPs) that reflected their degree of association and colocalization with Kv4.2 in wild-type mouse and rat brains. These studies highlight the insights that can be gained by performing detailed immunohistochemical analyses of Kv channel knockout mouse brains. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

Aerosol-delivered programmed cell death 4 enhanced apoptosis, controlled cell cycle and suppressed AP-1 activity in the lungs of AP-1 luciferase reporter mice.

Science.gov (United States)

Hwang, S-K; Jin, H; Kwon, J T; Chang, S-H; Kim, T H; Cho, C-S; Lee, K H; Young, M R; Colburn, N H; Beck, G R; Yang, H-S; Cho, M-H

2007-09-01

The long-term survival of lung cancer patients treated with conventional therapies remains poor and therefore the need for novel approaches remains high. This has led to the re-emergence of aerosol delivery as a therapeutic intervention. In this study, glucosylated polyethylenimine (GPEI) was used as carrier to investigate programmed cell death 4 (PDCD4) and PDCD4 mutant (D418A), an eIF4A-binding mutant, on PDCD4-related signaling and activator protein-1 (AP-1) activity in the lungs of AP-1 luciferase reporter mice. After confirming the efficiency of GPEI as a carrier in lungs, the effects of aerosol-delivered PDCD4 were investigated in AP-1 luciferase reporter mice. Aerosol delivery of GPEI/PDCD4 through a nose-only inhalation facilitated the apoptosis of lungs whereas aerosol PDCD4 mutant did not. Also, such aerosol delivery regulated proteins relevant to cell-cycle control and suppressed AP-1 activity. Results obtained by western blot analysis, immunohistochemistry, luciferase assay and deoxynucleotidyl-transferase-mediated nick end labeling study suggest that combined actions such as facilitating apoptosis, controlling cell cycle and suppression of AP-1 activity by PDCD4 may provide useful tool for designing lung tumor prevention and treatment by which PDCD4 functions as a transformation suppressor in the future.

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

DEFF Research Database (Denmark)

Jepps, Thomas Andrew; Greenwood, Iain A; Moffatt, James D

2009-01-01

that K(v)7.x especially K(v)7.4 and K(v)7.5 are expressed in different regions of the murine gastrointestinal tract and blockers of K(v)7 channels augment inherent contractile activity. Drugs that selectively block K(v)7.4/7.5 might be promising therapeutics for the treatment of motility disorders...

The acrylamide (S)-1 differentially affects Kv7 (KCNQ) potassium channels

DEFF Research Database (Denmark)

Bentzen, Bo Hjorth; Schmitt, Nicole; Calloe, Kirstine

2006-01-01

The family of Kv7 (KCNQ) potassium channels consists of five members. Kv7.2 and 3 are the primary molecular correlates of the M-current, but also Kv7.4 and Kv7.5 display M-current characteristics. M-channel modulators include blockers (e.g., linopirdine) for cognition enhancement and openers (e.g...

Voltage dependent potassium channel remodeling in murine intestinal smooth muscle hypertrophy induced by partial obstruction.

Science.gov (United States)

Liu, Dong-Hai; Huang, Xu; Guo, Xin; Meng, Xiang-Min; Wu, Yi-Song; Lu, Hong-Li; Zhang, Chun-Mei; Kim, Young-chul; Xu, Wen-Xie

2014-01-01

Partial obstruction of the small intestine causes obvious hypertrophy of smooth muscle cells and motility disorder in the bowel proximate to the obstruction. To identify electric remodeling of hypertrophic smooth muscles in partially obstructed murine small intestine, the patch-clamp and intracellular microelectrode recording methods were used to identify the possible electric remodeling and Western blot, immunofluorescence and immunoprecipitation were utilized to examine the channel protein expression and phosphorylation level changes in this research. After 14 days of obstruction, partial obstruction caused obvious smooth muscle hypertrophy in the proximally located intestine. The slow waves of intestinal smooth muscles in the dilated region were significantly suppressed, their amplitude and frequency were reduced, whilst the resting membrane potentials were depolarized compared with normal and sham animals. The current density of voltage dependent potassium channel (KV) was significantly decreased in the hypertrophic smooth muscle cells and the voltage sensitivity of KV activation was altered. The sensitivity of KV currents (IKV) to TEA, a nonselective potassium channel blocker, increased significantly, but the sensitivity of IKv to 4-AP, a KV blocker, stays the same. The protein levels of KV4.3 and KV2.2 were up-regulated in the hypertrophic smooth muscle cell membrane. The serine and threonine phosphorylation levels of KV4.3 and KV2.2 were significantly increased in the hypertrophic smooth muscle cells. Thus this study represents the first identification of KV channel remodeling in murine small intestinal smooth muscle hypertrophy induced by partial obstruction. The enhanced phosphorylations of KV4.3 and KV2.2 may be involved in this process.

Design of low impedance busbar for 10 kV, 100A 4H-SiC MOSFET short-circuit tester using axial capacitors

DEFF Research Database (Denmark)

Eni, Emanuel-Petre; Kerekes, Tamas; Uhrenfeldt, Christian

2015-01-01

, reduce the complexity and size of the setup by avoiding series connection of DC-link capacitor and by employing capacitors with voltage ratings above 10 kV. Obtaining a low inductance at such voltage levels is challenging, considering the required clearance distances, the lack of radial style capacitor...... rated for 10 kV on the market, the package design of CREE 10 kV 10 A 4H-SiC MOSFETs and the required space for the device heater. Ansys Q3D is used in order to extract the parasitic components from the design. Custom designed aluminum cans for 15 kV axial capacitors are used in order to minimize...

Nuclear AP4A-binding activity of sea urchin embryos changes in relation to the initiation of S phase

International Nuclear Information System (INIS)

Morioka, M.; Shimada, H.

1986-01-01

The AP 4 A-binding activity of sea urchin embryos was studied using radioactively labelled diadenosine 5', 5'''-P 1 ,P 4 -tetraphosphate (Ap 4 A). Among various subcellular components that can bind [ 3 H]AP 4 A, nuclei alone showed the highly specific Ap 4 A-binding activity which was not influenced by the presence of AP 4 A, AP 5 A and GP 4 G. The addition of an excess amount of ATP only slightly reduced the binding of [ 3 H]AP 4 A to the nuclei. It was found that AP 4 A binds to the residual proteinaceous structure of nuclei which was resistant to the extraction with 2 M NaCl. The nuclear AP 4 A-binding activity fluctuated cyclically during each cell cycle, with at transient increase at the beginning of S phase followed by an abrupt-decrease within 10 min. When the initiation of S phase was blocked, the increase in the AP 4 A-binding activity was also prevented. It seems that the binding of AP 4 A to the nuclear structural protein is involved in the initiation of S phase

A 6.4 kV pulse generator with transformations

International Nuclear Information System (INIS)

Bastein, W.L.

1989-01-01

The possibility has been investigated to perform a pulse generator which generates pulse for the cathode of the injector of the NIKHEF electron accelerator, which generates pulses of 6.4 kV with sides of 100 ns a duration of 2 to 50 microseconds and a frequency of 2500 Hz. The voltage ripple should be smaller than frequency part and one for the high-frequency part, it is possible to generate a pulse which fulfills the requirements with regard to the sides. However installing an tuning of circuits in order to obtain a sufficiently flat pulse will cost much time. Moreover the losses are such high that it deserves recommendation to investigate the possibility ot generate the pulse with a number of MOSFets connected in series. (author). 8 refs.; 8 figs.; 14 photos; 1 tab

Study and field verification of the effects of removing closing resistors from 500 kV circuit breakers

International Nuclear Information System (INIS)

Selin, D.A.; Agrawal, B.L.; Farmer, R.G.; Demcko, J.A.

1992-01-01

Closing resistors in EHV circuit breakers are frequently used to reduce switching transients on lines thus preventing flashovers during line energization. Maintenance and failures of such closing resistors can be costly and reduce transmission system reliability. For these reasons, APS conducted an investigation into the technical feasibility of operating its 500 kV without closing resistors. This paper describes study results of removing closing resistors from 500 kV breakers in a system which employs older technology silicon carbide type surge arresters. The paper also describes results of field tests of the expected flashover rates calculated in the study. These field tests involve repeatedly energizing a 258 mile 500 kV line using a breaker in which the closing resistors are disabled. Transient overvoltages captured during the tests are compared with predicted overvoltages. The study concludes that closing resistors may be removed from the subject system without unacceptable consequences

Mechanistic Basis for Type 2 Long QT Syndrome Caused by KCNH2 Mutations that Disrupt Conserved Arginine Residue in the Voltage Sensor

Science.gov (United States)

McBride, Christie M.; Smith, Ashley M.; Smith, Jennifer L.; Reloj, Allison R.; Velasco, Ellyn J.; Powell, Jonathan; Elayi, Claude S.; Bartos, Daniel C.; Burgess, Don E.

2013-01-01

KCNH2 encodes the Kv11.1 channel, which conducts the rapidly activating delayed rectifier K+ current (IKr) in the heart. KCNH2 mutations cause type 2 long QT syndrome (LQT2), which increases the risk for life-threatening ventricular arrhythmias. LQT2 mutations are predicted to prolong the cardiac action potential (AP) by reducing IKr during repolarization. Kv11.1 contains several conserved basic amino acids in the fourth transmembrane segment (S4) of the voltage sensor that are important for normal channel trafficking and gating. This study sought to determine the mechanism(s) by which LQT2 mutations at conserved arginine residues in S4 (R531Q, R531W or R534L) alter Kv11.1 function. Western blot analyses of HEK293 cells transiently expressing R531Q, R531W or R534L suggested that only R534L inhibited Kv11.1 trafficking. Voltage-clamping experiments showed that R531Q or R531W dramatically altered Kv11.1 current (IKv11.1) activation, inactivation, recovery from inactivation and deactivation. Coexpression of wild type (to mimic the patients’ genotypes) mostly corrected the changes in IKv11.1 activation and inactivation, but deactivation kinetics were still faster. Computational simulations using a human ventricular AP model showed that accelerating deactivation rates was sufficient to prolong the AP, but these effects were minimal compared to simply reducing IKr. These are the first data to demonstrate that coexpressing wild type can correct activation and inactivation dysfunction caused by mutations at a critical voltage-sensing residue in Kv11.1. We conclude that some Kv11.1 mutations might accelerate deactivation to cause LQT2 but that the ventricular AP duration is much more sensitive to mutations that decrease IKr. This likely explains why most LQT2 mutations are nonsense or trafficking-deficient. PMID:23546015

Functional interactions at the interface between voltage-sensing and pore domains in the Shaker K(v) channel.

Science.gov (United States)

Soler-Llavina, Gilberto J; Chang, Tsg-Hui; Swartz, Kenton J

2006-11-22

Voltage-activated potassium (K(v)) channels contain a central pore domain that is partially surrounded by four voltage-sensing domains. Recent X-ray structures suggest that the two domains lack extensive protein-protein contacts within presumed transmembrane regions, but whether this is the case for functional channels embedded in lipid membranes remains to be tested. We investigated domain interactions in the Shaker K(v) channel by systematically mutating the pore domain and assessing tolerance by examining channel maturation, S4 gating charge movement, and channel opening. When mapped onto the X-ray structure of the K(v)1.2 channel the large number of permissive mutations support the notion of relatively independent domains, consistent with crystallographic studies. Inspection of the maps also identifies portions of the interface where residues are sensitive to mutation, an external cluster where mutations hinder voltage sensor activation, and an internal cluster where domain interactions between S4 and S5 helices from adjacent subunits appear crucial for the concerted opening transition.

KCNE1 constrains the voltage sensor of Kv7.1 K+ channels.

Directory of Open Access Journals (Sweden)

Liora Shamgar

Full Text Available 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.

S1 constrains S4 in the voltage sensor domain of Kv7.1 K+ channels.

Directory of Open Access Journals (Sweden)

Yoni Haitin

Full Text Available Voltage-gated K(+ channels comprise a central pore enclosed by four voltage-sensing domains (VSDs. While movement of the S4 helix is known to couple to channel gate opening and closing, the nature of S4 motion is unclear. Here, we substituted S4 residues of Kv7.1 channels by cysteine and recorded whole-cell mutant channel currents in Xenopus oocytes using the two-electrode voltage-clamp technique. In the closed state, disulfide and metal bridges constrain residue S225 (S4 nearby C136 (S1 within the same VSD. In the open state, two neighboring I227 (S4 are constrained at proximity while residue R228 (S4 is confined close to C136 (S1 of an adjacent VSD. Structural modeling predicts that in the closed to open transition, an axial rotation (approximately 190 degrees and outward translation of S4 (approximately 12 A is accompanied by VSD rocking. This large sensor motion changes the intra-VSD S1-S4 interaction to an inter-VSD S1-S4 interaction. These constraints provide a ground for cooperative subunit interactions and suggest a key role of the S1 segment in steering S4 motion during Kv7.1 gating.

Protein kinase A stimulates Kv7.1 surface expression by regulating Nedd4-2-dependent endocytic trafficking

DEFF Research Database (Denmark)

Andersen, Martin Nybo; Hefting, Louise Leth; Steffensen, Annette Buur

2015-01-01

The potassium channel Kv7.1 plays critical physiological roles in both heart and epithelial tissues. In heart, Kv7.1 and the accessory subunit KCNE1 forms the IKs current, which is enhanced by PKA mediated phosphorylation. The observed current increase requires both phosphorylation of Kv7.......1 and the presence of KCNE1. However, PKA also stimulates Kv7.1 currents in epithelial tissues, such as colon, where the channel does not co-assemble with KCNE1. Here, we demonstrate that PKA activity significantly impacts the subcellular localization of Kv7.1 in Madin Darby Canine Kidney cells. While PKA inhibition...... reduced the fraction of channels at the cell surface, PKA activation increased it. We show that PKA inhibition lead to intracellular accumulation of Kv7.1 in late endosomes/lysosomes. By mass spectroscopy we identified eight phosphorylated residues on Kv7.1, however, none appeared to play a role...

Mechanistic basis for type 2 long QT syndrome caused by KCNH2 mutations that disrupt conserved arginine residues in the voltage sensor.

Science.gov (United States)

McBride, Christie M; Smith, Ashley M; Smith, Jennifer L; Reloj, Allison R; Velasco, Ellyn J; Powell, Jonathan; Elayi, Claude S; Bartos, Daniel C; Burgess, Don E; Delisle, Brian P

2013-05-01

KCNH2 encodes the Kv11.1 channel, which conducts the rapidly activating delayed rectifier K+ current (I Kr) in the heart. KCNH2 mutations cause type 2 long QT syndrome (LQT2), which increases the risk for life-threatening ventricular arrhythmias. LQT2 mutations are predicted to prolong the cardiac action potential (AP) by reducing I Kr during repolarization. Kv11.1 contains several conserved basic amino acids in the fourth transmembrane segment (S4) of the voltage sensor that are important for normal channel trafficking and gating. This study sought to determine the mechanism(s) by which LQT2 mutations at conserved arginine residues in S4 (R531Q, R531W or R534L) alter Kv11.1 function. Western blot analyses of HEK293 cells transiently expressing R531Q, R531W or R534L suggested that only R534L inhibited Kv11.1 trafficking. Voltage-clamping experiments showed that R531Q or R531W dramatically altered Kv11.1 current (I Kv11.1) activation, inactivation, recovery from inactivation and deactivation. Coexpression of wild type (to mimic the patients' genotypes) mostly corrected the changes in I Kv11.1 activation and inactivation, but deactivation kinetics were still faster. Computational simulations using a human ventricular AP model showed that accelerating deactivation rates was sufficient to prolong the AP, but these effects were minimal compared to simply reducing I Kr. These are the first data to demonstrate that coexpressing wild type can correct activation and inactivation dysfunction caused by mutations at a critical voltage-sensing residue in Kv11.1. We conclude that some Kv11.1 mutations might accelerate deactivation to cause LQT2 but that the ventricular AP duration is much more sensitive to mutations that decrease I Kr. This likely explains why most LQT2 mutations are nonsense or trafficking-deficient.

Algoritmo para el 4ap haciendo uso de la metaheuristica sistema hormiga

Directory of Open Access Journals (Sweden)

Manuel Vicente Centeno Romero

2008-07-01

Full Text Available La metaheurística sistema hormiga consiste en la analogía entre el procedimiento que utilizan las hormigas reales para la búsqueda de alimentos, encontrando la ruta más corta, y los problemas de optimización combinatoria para encontrar la mejor solución. Entre estos problemas se encuentra el de asignación multidimensional (mAP, el cual es un problema NP-difícil para m > 2. En la actualidad no se ha desarrollado trabajo alguno sobre el 4AP (mAP con m=4, tampoco existe publicación sobre la aplicación del sistema hormiga para el mAP. En este trabajo se desarrolló un software que hace uso de la metaheurística sistema hormiga para encontrar la mejor solución o aproximada al 4AP, con problemas generados aleatoriamente. Se implementó una metodología híbrida entre la metodología de Investigación de Operaciones descrita por Taha (1991 y la ingeniería de software (1990. El número de asignaciones tomadas en cuenta para verificar qué tan buenas son las soluciones arrojadas por el software, varía desde n=2 hasta n=25, obteniéndose soluciones exactas para 2 £ n £ 6, ya que al compararse dichas soluciones con las dadas por XPRESS (software de programación lineal que se usa para resolver modelos matemáticos se observa la igualdad en los resultados. Para n _ 7, XPRESS (la versión utilizada no ofrece respuesta alguna, pero el software desarrollado arroja buenos resultados en un tiempo computacional razonable, considerando el número de asignaciones que se procesan en cada n. The metaheuristic ant system consists on the analogy among the procedure used by the real ants for searching food, for finding the shortest route; and the problems of combinatoria optimization to find the best solution. Among these problems we can find the multidimensional assignment problem (mAP, which is a NP-difficult problem for m > 2. At the present time, there isn‘t any work that has been developed, on this topic about the 4AP (mAP with m=4, neither

Bladder contractility is modulated by Kv7 channels in pig detrusor

DEFF Research Database (Denmark)

Svalø, Julie; Bille, Michala; Parameswaran Theepakaran, Neeraja

2013-01-01

Kv7 channels are involved in smooth muscle relaxation, and accordingly we believe that they constitute potential targets for the treatment of overactive bladder syndrome. We have therefore used myography to examine the function of Kv7 channels in detrusor, i.e. pig bladder, with a view...... relaxation, suggesting that Kv7.2 and/or Kv7.4 channels constitute the subtypes that are relevant to bladder contractility. The effects of retigabine and ML213 were attenuated by pre-incubation with 10µM XE991 (Kv7.1-7.5 channel blocker) (P...

Differential expression of the Kv1 voltage-gated potassium channel family in the rat nephron.

Science.gov (United States)

Carrisoza-Gaytán, Rolando; Salvador, Carolina; Diaz-Bello, Beatriz; Escobar, Laura I

2014-10-01

Several potassium (K(+)) channels contribute to maintaining the resting membrane potential of renal epithelial cells. Apart from buffering the cell membrane potential and cell volume, K(+) channels allow sodium reabsorption in the proximal tubule (PT), K(+) recycling and K(+) reabsorption in the thick ascending limb (TAL) and K(+) secretion and K(+) reabsorption in the distal convoluted tubule (DCT), connecting tubule (CNT) and collecting duct. Previously, we identified Kv.1.1, Kv1.3 and Kv1.6 channels in collecting ducts of the rat inner medulla. We also detected intracellular Kv1.3 channel in the acid secretory intercalated cells, which is trafficked to the apical membrane in response to dietary K(+) to function as a secretory K(+) channel. In this work we sought to characterize the expression of all members of the Kv1 family in the rat nephron. mRNA and protein expression were detected for all Kv1 channels. Immunoblots identified differential expression of each Kv1 in the cortex, outer and inner medulla. Immunofluorescence labeling detected Kv1.5 in Bowman´s capsule and endothelial cells and Kv1.7 in podocytes, endothelial cells and macula densa in glomeruli; Kv1.4, Kv1.5 and Kv1.7 in PT; Kv1.2, Kv1.4 and Kv1.6 in TAL; Kv1.1, Kv1.4 and Kv1.6 in DCT and CNT and Kv1.3 in DCT, and all the Kv1 family in the cortical and medullary collecting ducts. Recently, some hereditary renal syndromes have been attributed to mutations in K(+) channels. Our results expand the repertoire of K(+) channels that contribute to K(+) homeostasis to include the Kv1 family.

Voltage dependent potassium channel remodeling in murine intestinal smooth muscle hypertrophy induced by partial obstruction.

Directory of Open Access Journals (Sweden)

Dong-Hai Liu

Full Text Available Partial obstruction of the small intestine causes obvious hypertrophy of smooth muscle cells and motility disorder in the bowel proximate to the obstruction. To identify electric remodeling of hypertrophic smooth muscles in partially obstructed murine small intestine, the patch-clamp and intracellular microelectrode recording methods were used to identify the possible electric remodeling and Western blot, immunofluorescence and immunoprecipitation were utilized to examine the channel protein expression and phosphorylation level changes in this research. After 14 days of obstruction, partial obstruction caused obvious smooth muscle hypertrophy in the proximally located intestine. The slow waves of intestinal smooth muscles in the dilated region were significantly suppressed, their amplitude and frequency were reduced, whilst the resting membrane potentials were depolarized compared with normal and sham animals. The current density of voltage dependent potassium channel (KV was significantly decreased in the hypertrophic smooth muscle cells and the voltage sensitivity of KV activation was altered. The sensitivity of KV currents (IKV to TEA, a nonselective potassium channel blocker, increased significantly, but the sensitivity of IKv to 4-AP, a KV blocker, stays the same. The protein levels of KV4.3 and KV2.2 were up-regulated in the hypertrophic smooth muscle cell membrane. The serine and threonine phosphorylation levels of KV4.3 and KV2.2 were significantly increased in the hypertrophic smooth muscle cells. Thus this study represents the first identification of KV channel remodeling in murine small intestinal smooth muscle hypertrophy induced by partial obstruction. The enhanced phosphorylations of KV4.3 and KV2.2 may be involved in this process.

Cloning and Molecular Characterization of the Schistosoma mansoni Genes RbAp48 and Histone H4

Directory of Open Access Journals (Sweden)

Patrícia P Souza

2002-10-01

Full Text Available The human nuclear protein RbAp48 is a member of the tryptophan/aspartate (WD repeat family, which binds to the retinoblastoma (Rb protein. It also corresponds to the smallest subunit of the chromatin assembly factor and is able to bind to the helix 1 of histone H4, taking it to the DNA in replication. A cDNA homologous to the human gene RbAp48 was isolated from a Schistosoma mansoni adult worm library and named SmRbAp48. The full length sequence of SmRbAp48 cDNA is 1036 bp long, encoding a protein of 308 amino acids. The transcript of SmRbAp48 was detected in egg, cercariae and schistosomulum stages. The protein shows 84% similarity with the human RbAp48, possessing four WD repeats on its C-terminus. A hypothetical tridimensional structure for the SmRbAp48 C-terminal domain was constructed by computational molecular modeling using the b-subunit of the G protein as a model. To further verify a possible interaction between SmRbAp48 and S. mansoni histone H4, the histone H4 gene was amplified from adult worm genomic DNA using degenerated primers. The gene fragment of SmH4 is 294 bp long, encoding a protein of 98 amino acids which is 100% identical to histone H4 from Drosophila melanogaster.

Center for Geometrisk Metrologi, CGM ApS

DEFF Research Database (Denmark)

De Chiffre, Leonardo

Denne årsberetning omfatter CGM ApS' akkrediterede virksomhed i kalenderåret 2002. Årsberetningen er udarbejdet til DANAK (Dansk Akkreditering, Erhvervsfremme Styrelsen), som led i opfyldelsen af laboratoriets informationspligt i henhold til gældende regler (Teknisk Forskrift Nr. TF4 af 2000...

TLR4-NOX4-AP-1 signaling mediates lipopolysaccharide-induced CXCR6 expression in human aortic smooth muscle cells

International Nuclear Information System (INIS)

Patel, Devang N.; Bailey, Steven R.; Gresham, John K.; Schuchman, David B.; Shelhamer, James H.; Goldstein, Barry J.; Foxwell, Brian M.; Stemerman, Michael B.; Maranchie, Jodi K.; Valente, Anthony J.; Mummidi, Srinivas; Chandrasekar, Bysani

2006-01-01

CXCL16 is a transmembrane non-ELR CXC chemokine that signals via CXCR6 to induce aortic smooth muscle cell (ASMC) proliferation. While bacterial lipopolysaccharide (LPS) has been shown to stimulate CXCL16 expression in SMC, its effects on CXCR6 are not known. Here, we demonstrate that LPS upregulates CXCR6 mRNA, protein, and surface expression in human ASMC. Inhibition of TLR4 with neutralizing antibodies or specific siRNA interference blocked LPS-mediated CXCR6 expression. LPS stimulated both AP-1 (c-Fos, c-Jun) and NF-κB (p50 and p65) activation, but only inhibition of AP-1 attenuated LPS-induced CXCR6 expression. Using dominant negative expression vectors and siRNA interference, we demonstrate that LPS induces AP-1 activation via MyD88, TRAF6, ERK1/2, and JNK signaling pathways. Furthermore, the flavoprotein inhibitor diphenyleniodonium chloride significantly attenuated LPS-mediated AP-1-dependent CXCR6 expression, as did inhibition of NOX4 NADPH oxidase by siRNA. Finally, CXCR6 knockdown inhibited CXCL16-induced ASMC proliferation. These results demonstrate that LPS-TLR4-NOX4-AP-1 signaling can induce CXCR6 expression in ASMC, and suggest that the CXCL16-CXCR6 axis may be an important proinflammatory pathway in the pathogenesis of atherosclerosis

A polyether biotoxin binding site on the lipid-exposed face of the pore domain of Kv channels revealed by the marine toxin gambierol

Science.gov (United States)

Kopljar, Ivan; Labro, Alain J.; Cuypers, Eva; Johnson, Henry W. B.; Rainier, Jon D.; Tytgat, Jan; Snyders, Dirk J.

2009-01-01

Gambierol is a marine polycyclic ether toxin belonging to the group of ciguatera toxins. It does not activate voltage-gated sodium channels (VGSCs) but inhibits Kv1 potassium channels by an unknown mechanism. While testing whether Kv2, Kv3, and Kv4 channels also serve as targets, we found that Kv3.1 was inhibited with an IC50 of 1.2 ± 0.2 nM, whereas Kv2 and Kv4 channels were insensitive to 1 μM gambierol. Onset of block was similar from either side of the membrane, and gambierol did not compete with internal cavity blockers. The inhibition did not require channel opening and could not be reversed by strong depolarization. Using chimeric Kv3.1–Kv2.1 constructs, the toxin sensitivity was traced to S6, in which T427 was identified as a key determinant. In Kv3.1 homology models, T427 and other molecular determinants (L348, F351) reside in a space between S5 and S6 outside the permeation pathway. In conclusion, we propose that gambierol acts as a gating modifier that binds to the lipid-exposed surface of the pore domain, thereby stabilizing the closed state. This site may be the topological equivalent of the neurotoxin site 5 of VGSCs. Further elucidation of this previously undescribed binding site may explain why most ciguatoxins activate VGSCs, whereas others inhibit voltage-dependent potassium (Kv) channels. This previously undescribed Kv neurotoxin site may have wide implications not only for our understanding of channel function at the molecular level but for future development of drugs to alleviate ciguatera poisoning or to modulate electrical excitability in general. PMID:19482941

Measurements of ground motion and magnet vibrations at the APS

International Nuclear Information System (INIS)

Shiltsev, V.

1996-01-01

This article presents results of ground motion and magnet vibrations measurements at the Advanced Photon Source. The experiments were done over a wide, frequency range (0-05-100 Hz) with the use of SM-3KV-type seismic probes from the Budker Institute of Nuclear Physics (Russia). Spectral power densities of vertical and horizontal motions of the APS hall floor and quadrupoles on regular supports were obtained. Also investigated were magnet vibrations induced by designed cooling water flow and spectral characteristics of spatial correlation of the quadrupole vibrations at different sectors of the ring. The influence of personnel activity in the hall and traffic under the ring on the slow motion of storage ring elements were observed. Amplitudes of vibrations at the APS are compared with results of seismic measurements at some other accelerators

Calcineurin Dysregulation Underlies Spinal Cord Injury-Induced K+ Channel Dysfunction in DRG Neurons.

Science.gov (United States)

Zemel, Benjamin M; Muqeem, Tanziyah; Brown, Eric V; Goulão, Miguel; Urban, Mark W; Tymanskyj, Stephen R; Lepore, Angelo C; Covarrubias, Manuel

2017-08-23

Dysfunction of the fast-inactivating Kv3.4 potassium current in dorsal root ganglion (DRG) neurons contributes to the hyperexcitability associated with persistent pain induced by spinal cord injury (SCI). However, the underlying mechanism is not known. In light of our previous work demonstrating modulation of the Kv3.4 channel by phosphorylation, we investigated the role of the phosphatase calcineurin (CaN) using electrophysiological, molecular, and imaging approaches in adult female Sprague Dawley rats. Pharmacological inhibition of CaN in small-diameter DRG neurons slowed repolarization of the somatic action potential (AP) and attenuated the Kv3.4 current. Attenuated Kv3.4 currents also exhibited slowed inactivation. We observed similar effects on the recombinant Kv3.4 channel heterologously expressed in Chinese hamster ovary cells, supporting our findings in DRG neurons. Elucidating the molecular basis of these effects, mutation of four previously characterized serines within the Kv3.4 N-terminal inactivation domain eliminated the effects of CaN inhibition on the Kv3.4 current. SCI similarly induced concurrent Kv3.4 current attenuation and slowing of inactivation. Although there was little change in CaN expression and localization after injury, SCI induced upregulation of the native regulator of CaN 1 (RCAN1) in the DRG at the transcript and protein levels. Consistent with CaN inhibition resulting from RCAN1 upregulation, overexpression of RCAN1 in naive DRG neurons recapitulated the effects of pharmacological CaN inhibition on the Kv3.4 current and the AP. Overall, these results demonstrate a novel regulatory pathway that links CaN, RCAN1, and Kv3.4 in DRG neurons. Dysregulation of this pathway might underlie a peripheral mechanism of pain sensitization induced by SCI. SIGNIFICANCE STATEMENT Pain sensitization associated with spinal cord injury (SCI) involves poorly understood maladaptive modulation of neuronal excitability. Although central mechanisms have

Functional analysis of Kv1.2 and paddle chimera Kv channels in planar lipid bilayers

Science.gov (United States)

Tao, Xiao; MacKinnon, Roderick

2010-01-01

Summary Voltage-dependent K+ channels play key roles in shaping electrical signaling in both excitable as well as non-excitable cells. These channels open and close in response to the voltage changes across the cell membrane. Many studies have been carried out in order to understand the voltage sensing mechanism. Our laboratory recently determined the atomic structures of a mammalian voltage-dependent K+ channel Kv1.2 and a mutant of Kv1.2 named the ‘paddle-chimera’ channel, in which the voltage sensor paddle was transferred from Kv2.1 to Kv1.2. These two structures provide atomic descriptions of voltage-dependent channels with unprecedented clarity. Until now the functional integrity of these two channels biosynthesized in yeast cells have not been assessed. Here we report the electrophysiological and pharmacological properties of Kv1.2 and the paddle chimera channels in planar lipid bilayers. We demonstrate that Pichia yeast produce ‘normally functioning’ mammalian voltage-dependent K+ channels with qualitatively similar features to the Shaker K+ channel in the absence of the N-terminal inactivation gate, and that the paddle chimera mutant channel functions as well as Kv1.2. We find, however, that in several respects the Kv1.2 channel exhibits functional properties that are distinct from Kv1.2 channels reported in the literature. PMID:18638484

Ectopic AP4 expression induces cellular senescence via activation of p53 in long-term confluent retinal pigment epithelial cells.

Science.gov (United States)

Wang, Yiping; Wong, Matthew Man-Kin; Zhang, Xiaojian; Chiu, Sung-Kay

2015-11-15

When cells are grown to confluence, cell-cell contact inhibition occurs and drives the cells to enter reversible quiescence rather than senescence. Confluent retinal pigment epithelial (RPE) cells exhibiting contact inhibition was used as a model in this study to examine the role of overexpression of transcription factor AP4, a highly expressed transcription factor in many types of cancer, in these cells during long-term culture. We generated stable inducible RPE cell clones expressing AP4 or AP4 without the DNA binding domain (DN-AP4) and observed that, when cultured for 24 days, RPE cells with a high level of AP4 exhibit a large, flattened morphology and even cease proliferating; these changes were not observed in DN-AP4-expressing cells or non-induced cells. In addition, AP4-expressing cells exhibited senescence-associated β-galactosidase activity and the senescence-associated secretory phenotype. We demonstrated that the induced cellular senescence was mediated by enhanced p53 expression and that AP4 regulates the p53 gene by binding directly to two of the three E-boxes present on the promoter of the p53 gene. Moreover, we showed that serum is essential for AP4 in inducing p53-associated cellular senescence. Collectively, we showed that overexpression of AP4 mediates cellular senescence involving in activation of p53 in long-term post-confluent RPE cells. Copyright © 2015 Elsevier Inc. All rights reserved.

Determination of L-AP4-bound human mGlu8 receptor amino terminal domain structure and the molecular basis for L-AP4’s group III mGlu receptor functional potency and selectivity

Energy Technology Data Exchange (ETDEWEB)

Schkeryantz, Jeffery M.; Chen, Qi; Ho, Joseph D.; Atwell, Shane; Zhang, Aiping; Vargas, Michelle C.; Wang, Jing; Monn, James A.; Hao, Junliang (Lilly)

2018-02-01

Here, L-2-Amino-4-phosphonobutyric acid (L-AP4) is a known potent and selective agonist for the Group III mGlu receptors. However, it does not show any selectivity among the individual group III mGlu subtypes. In order to understand the molecular basis for this group selectivity, we solved the first human mGlu8 amino terminal domain (ATD) crystal structures in complex with L-glu and L-AP4. In comparison with other published L-glu-bound mGlu ATD structures, we have observed L-glu binds in a significantly different manner in mGlu1. Furthermore, these new structures provided evidence that both the electronic and steric nature of the distal phosphate of L-AP4 contribute to its exquisite Group III functional agonist potency and selectivity.

Dispersion of repolarization and refractoriness are determinants of arrhythmia phenotype in transgenic mice with long QT.

Science.gov (United States)

London, Barry; Baker, Linda C; Petkova-Kirova, Polina; Nerbonne, Jeanne M; Choi, Bum-Rak; Salama, Guy

2007-01-01

Enhanced dispersion of repolarization (DR) and refractoriness may be a unifying mechanism central to arrhythmia genesis in the long QT (LQT) syndrome. The role of DR in promoting arrhythmias was investigated in several strains of molecularly engineered mice: (a) Kv4.2 dominant negative transgenic (Kv4.2DN) that lacks the fast component of the transient outward current, I(to,f), have action potential (AP) and QT prolongation, but no spontaneous arrhythmias, (b) Kv1.4 targeted mice (Kv1.4-/-) that lack the slow component of I(to) (I(to,s)), have no QT prolongation and no spontaneous arrhythmias, and (c) double transgenic (Kv4.2DN x Kv1.4-/-) mice that lack both I(to,f) and I(to,s), have AP and QT prolongation, and spontaneous ventricular tachyarrhythmias. Hearts were perfused, stained with di-4-ANEPPS and optically mapped. Activation patterns and conduction velocities were similar between the strains but AP duration at 75% recovery (APD75) was longer in Kv4.2DN (28.0 +/- 2.5 ms, P mice than controls (20.3 +/- 1.0 ms, n = 5). Dispersion of refractoriness between apex and base was markedly reduced in Kv4.2DN (0.3 +/- 0.5 ms, n = 6, P mice compared with controls (10 +/- 2 ms, n = 5). A premature pulse elicited ventricular tachycardia (VT) in Kv1.4-/- (n = 4/5) and Kv4.2DN x Kv1.4-/- hearts (n = 5/5) but not Kv4.2DN hearts (n = 0/6). Voltage-clamp recordings showed that I(to,f) was 30% greater in myocytes from the apex than base which may account for the absence of DR in Kv4.2DN mice. Thus, dispersion of repolarization (DR) appears to be an important determinant of arrhythmia vulnerability.

French 400 kV network

Energy Technology Data Exchange (ETDEWEB)

Pelissier, R

1965-11-01

A 400 kV transmission network has been constructed to carry hydroelectric power from the Alps and the Massif Central to Paris at peak hours and to carry power in the reverse direction in off-peak hours. A double circuit-ring at 400 kV encircling the Paris region is also nearing completion. Measures have to be taken to counter the very high short-circuit currents in such a network. A 730 kV network will eventually become necessary. The consequent multiplicity of transmission voltages will give rise to further problems. Collaboration with neighboring countries is envisaged. The problems of stability and synchronization posed by the new system are described and solutions suggested. The new circuit-breaking requirements are discussed, and details of tower design for 400 kV and 730 kV are given.

Measurements of ground motion and magnets vibrations at the APS

International Nuclear Information System (INIS)

Shil'tsev, V.D.

1994-01-01

This article presents results of ground motion and magnets vibrations measurements at the Advanced Photon Source. The experiments were done over wide frequency range 0.05-100 Hz with use of SM-3KV type seismic probes from Budker Institute of Nuclear Physics (Russia). Spectral power densities of vertical and horizontal motions of the APS hall floor and quadrupoles on regular supports were obtained. There were also investigated magnets vibrations induced by designed cooling water flow and spectral characteristics of spatial correlation of the quads vibration at different sectors of the ring. Influence of personnel activity in the hall and traffic under the ring on slow motion of storage ring elements were observed. Amplitudes of vibrations at the APS are compared with results of seismic measurements at some other accelerators. 9 refs.; 10 figs.; 1 tab

On the prohibition of automatic redundant power supply of 6 and 0.4 kV auxiliary sections at Leningrad NPP

International Nuclear Information System (INIS)

Mokeev, S.F.

1987-01-01

At Leningrad NPP the automatic switching on of the auxiliary power supply sources of 6 and 0.4 kV is prohibited to provide personnel safety and preserve destruction of electroequipment. With excess of current maximum value in the 6 kV section immediate detachment of all electric motors occurs. At that moment by the switchers detechment emergency signal it occurs immediate swithing on of auxiliary systems or emergency switching on of auxiliary supply of the main circulating pumps, that insreases abruptly operation reliability of plant technological department

Mitochondrial ultrastructure and glucose signaling pathways attributed to the Kv1.3 ion channel

Directory of Open Access Journals (Sweden)

Christopher P. Kovach

2016-05-01

Full Text Available 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 is 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 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 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 understand how

Expression and function of Kv1.1 potassium channels in human atria from patients with atrial fibrillation.

Science.gov (United States)

Glasscock, Edward; Voigt, Niels; McCauley, Mark D; Sun, Qiang; Li, Na; Chiang, David Y; Zhou, Xiao-Bo; Molina, Cristina E; Thomas, Dierk; Schmidt, Constanze; Skapura, Darlene G; Noebels, Jeffrey L; Dobrev, Dobromir; Wehrens, Xander H T

2015-09-01

Voltage-gated Kv1.1 channels encoded by the Kcna1 gene are traditionally regarded as being neural-specific with no known expression or intrinsic functional role in the heart. However, recent studies in mice reveal low-level Kv1.1 expression in heart and cardiac abnormalities associated with Kv1.1-deficiency suggesting that the channel may have a previously unrecognized cardiac role. Therefore, this study tests the hypothesis that Kv1.1 channels are associated with arrhythmogenesis and contribute to intrinsic cardiac function. In intra-atrial burst pacing experiments, Kcna1-null mice exhibited increased susceptibility to atrial fibrillation (AF). The atria of Kcna1-null mice showed minimal Kv1 family ion channel remodeling and fibrosis as measured by qRT-PCR and Masson's trichrome histology, respectively. Using RT-PCR, immunocytochemistry, and immunoblotting, KCNA1 mRNA and protein were detected in isolated mouse cardiomyocytes and human atria for the first time. Patients with chronic AF (cAF) showed no changes in KCNA1 mRNA levels relative to controls; however, they exhibited increases in atrial Kv1.1 protein levels, not seen in paroxysmal AF patients. Patch-clamp recordings of isolated human atrial myocytes revealed significant dendrotoxin-K (DTX-K)-sensitive outward current components that were significantly increased in cAF patients, reflecting a contribution by Kv1.1 channels. The concomitant increases in Kv1.1 protein and DTX-K-sensitive currents in atria of cAF patients suggest that the channel contributes to the pathological mechanisms of persistent AF. These findings provide evidence of an intrinsic cardiac role of Kv1.1 channels and indicate that they may contribute to atrial repolarization and AF susceptibility.

Determination of prompt neutron decay constant of the AP-600 reactor core

International Nuclear Information System (INIS)

Surbakti, T.

1998-01-01

Determination of prompt neutron decay constant of the AP-600 reactor core has been performed using combination of two codes WIMS/D4 and Batan-2DIFF. The calculation was done at beginning of cycle and all of control rods pulled out. Cell generation from various kinds of core materials was done with 4 neutron energy group in 1-D transport code (WIMS/D4). The cell is considered for 1/4 fuel assembly in cluster model with square pitch arrange and then, the dimension of its unit cell is calculated. The unit cell consist of a fuel and moderator unit. The unit cell dimension as input data of WIMS/D4 code, called it annulus, is obtained from the equivalent unit cell. Macroscopic cross sections as output was used as input on neutron diffusion code Batan-2DIFF for core calculation as appropriate with three enrichment regions of the fuel of AP-600 core, namely 2, 2.5, and 3%. From result of diffusion code ( Batan-2DIFF) is obtained the value of delayed neutron fraction of 6.932E-03 and average prompt neutron life-time of 26.38 μs, so that the value of prompt neutron decay constant is 262.8 s-1. If it is compared the calculation result with the design value, the deviation are, for the design value of delayed neutron fraction is 7.5E-03, about 8% and the design value of average prompt neutron life time is 19.6 μs, about 34% respectively. The deviation because there are still unknown several core components of AP-600, so it didn't include in calculation yet

Single-Phase Bundle Flows Including Macroscopic Turbulence Model

Energy Technology Data Exchange (ETDEWEB)

Lee, Seung Jun; Yoon, Han Young [KAERI, Daejeon (Korea, Republic of); Yoon, Seok Jong; Cho, Hyoung Kyu [Seoul National University, Seoul (Korea, Republic of)

2016-05-15

To deal with various thermal hydraulic phenomena due to rapid change of fluid properties when an accident happens, securing mechanistic approaches as much as possible may reduce the uncertainty arising from improper applications of the experimental models. In this study, the turbulence mixing model, which is well defined in the subchannel analysis code such as VIPRE, COBRA, and MATRA by experiments, is replaced by a macroscopic k-e turbulence model, which represents the aspect of mathematical derivation. The performance of CUPID with macroscopic turbulence model is validated against several bundle experiments: CNEN 4x4 and PNL 7x7 rod bundle tests. In this study, the macroscopic k-e model has been validated for the application to subchannel analysis. It has been implemented in the CUPID code and validated against CNEN 4x4 and PNL 7x7 rod bundle tests. The results showed that the macroscopic k-e turbulence model can estimate the experiments properly.

SU-F-J-16: Planar KV Imaging Dose Reduction Study

Energy Technology Data Exchange (ETDEWEB)

Gershkevitsh, E; Zolotuhhin, D [North Estonia Medical Centre, Tallinn (Estonia)

2016-06-15

Purpose: IGRT has become an indispensable tool in modern radiotherapy with kV imaging used in many departments due to superior image quality and lower dose when compared to MV imaging. Many departments use manufacturer supplied protocols for imaging which are not always optimised between image quality and radiation dose (ALARA). Methods: Whole body phantom PBU-50 (Kyoto Kagaku ltd., Japan) for imaging in radiology has been imaged on Varian iX accelerator (Varian Medical Systems, USA) with OBI 1.5 system. Manufacturer’s default protocols were adapted by modifying kV and mAs values when imaging different anatomical regions of the phantom (head, thorax, abdomen, pelvis, extremities). Images with different settings were independently reviewed by two persons and their suitability for IGRT set-up correction protocols were evaluated. The suitable images with the lowest mAs were then selected. The entrance surface dose (ESD) for manufacturer’s default protocols and modified protocols were measured with RTI Black Piranha (RTI Group, Sweden) and compared. Image quality was also measured with kVQC phantom (Standard Imaging, USA) for different protocols. The modified protocols have been applied for clinical work. Results: For most cases optimized protocols reduced the ESD on average by a factor of 3(range 0.9–8.5). Further reduction in ESD has been observed by applying bow-tie filter designed for CBCT. The largest reduction in dose (12.2 times) was observed for Thorax lateral protocol. The dose was slightly increased (by 10%) for large pelvis AP protocol. Conclusion: Manufacturer’s default IGRT protocols could be optimised to reduce the ESD to the patient without losing the necessary image quality for patient set-up correction. For patient set-up with planar kV imaging the bony anatomy is mostly used and optimization should focus on this aspect. Therefore, the current approach with anthropomorphic phantom is more advantageous in optimization over standard kV quality

Loss-of-normal-feedwater sensitivity studies for AP600 behavior characterization

International Nuclear Information System (INIS)

Saiu, G.

1996-01-01

Activity concerning the development of a RELAP5/MOD3 model to simulate the Westinghouse Electric Corporation AP600 is summarized. The aim is to gain initial insight into the capability of RELAP5 to simulate the behavior of AP600 safety features. A-loss-of-normal-feedwater event is studied. Of the transients that must be investigated, this transient has been chosen to be one of the most relevant because the response of the AP600 to a loss-of-normal-feedwater event differs significantly from that of current pressurized water reactors in the extensive use of passive safety features peculiar to the AP600. Also, strong interactions among the AP600 safety systems, which should be further analyzed to permit full optimization of the system actuation logic and operation, are shown. Finally, a loss of normal feedwater without reactor scram, performed to investigate short-term plant behavior, shows that the pressure peak is affected by critical discharge flow coefficients applied to the pressurizer safety valves, while a relatively small reduction of the pressure peak is observed when both heat exchangers of the passive heat removal system are operating as opposed to the case in which only one is available. The data used for this study are derived from the Standard Safety Analysis Report configuration of the Westinghouse AP600 as of 1992

Expression and function of a CP339,818-sensitive K+ current in a subpopulation of putative nociceptive neurons from adult mouse trigeminal ganglia

Science.gov (United States)

Sforna, Luigi; D'Adamo, Maria Cristina; Servettini, Ilenio; Guglielmi, Luca; Pessia, Mauro; Franciolini, Fabio

2015-01-01

Trigeminal ganglion (TG) neurons are functionally and morphologically heterogeneous, and the molecular basis of this heterogeneity is still not fully understood. Here we describe experiments showing that a subpopulation of neurons expresses a delayed-rectifying K+ current (IDRK) with a characteristically high (nanomolar) sensitivity to the dihydroquinoline CP339,818 (CP). Although submicromolar CP has previously been shown to selectively block Kv1.3 and Kv1.4 channels, the CP-sensitive IDRK found in TG neurons could not be associated with either of these two K+ channels. It could neither be associated with Kv2.1 channels homomeric or heteromerically associated with the Kv9.2, Kv9.3, or Kv6.4 subunits, whose block by CP, tested using two-electrode voltage-clamp recordings from Xenopus oocytes, resulted in the low micromolar range, nor to the Kv7 subfamily, given the lack of blocking efficacy of 3 μM XE991. Within the group of multiple-firing neurons considered in this study, the CP-sensitive IDRK was preferentially expressed in a subpopulation showing several nociceptive markers, such as small membrane capacitance, sensitivity to capsaicin, and slow afterhyperpolarization (AHP); in these neurons the CP-sensitive IDRK controls the membrane resting potential, the firing frequency, and the AHP duration. A biophysical study of the CP-sensitive IDRK indicated the presence of two kinetically distinct components: a fast deactivating component having a relatively depolarized steady-state inactivation (IDRKf) and a slow deactivating component with a more hyperpolarized V1/2 for steady-state inactivation (IDRKs). PMID:25652918

Association between Rare Variants in AP4E1, a Component of Intracellular Trafficking, and Persistent Stuttering.

Science.gov (United States)

Raza, M Hashim; Mattera, Rafael; Morell, Robert; Sainz, Eduardo; Rahn, Rachel; Gutierrez, Joanne; Paris, Emily; Root, Jessica; Solomon, Beth; Brewer, Carmen; Basra, M Asim Raza; Khan, Shaheen; Riazuddin, Sheikh; Braun, Allen; Bonifacino, Juan S; Drayna, Dennis

2015-11-05

Stuttering is a common, highly heritable neurodevelopmental disorder characterized by deficits in the volitional control of speech. Whole-exome sequencing identified two heterozygous AP4E1 coding variants, c.1549G>A (p.Val517Ile) and c.2401G>A (p.Glu801Lys), that co-segregate with persistent developmental stuttering in a large Cameroonian family, and we observed the same two variants in unrelated Cameroonians with persistent stuttering. We found 23 other rare variants, including predicted loss-of-function variants, in AP4E1 in unrelated stuttering individuals in Cameroon, Pakistan, and North America. The rate of rare variants in AP4E1 was significantly higher in unrelated Pakistani and Cameroonian stuttering individuals than in population-matched control individuals, and coding variants in this gene are exceptionally rare in the general sub-Saharan West African, South Asian, and North American populations. Clinical examination of the Cameroonian family members failed to identify any symptoms previously reported in rare individuals carrying homozygous loss-of-function mutations in this gene. AP4E1 encodes the ε subunit of the heterotetrameric (ε-β4-μ4-σ4) AP-4 complex, involved in protein sorting at the trans-Golgi network. We found that the μ4 subunit of AP-4 interacts with NAGPA, an enzyme involved in the synthesis of the mannose 6-phosphate signal that targets acid hydrolases to the lysosome and the product of a gene previously associated with stuttering. These findings implicate deficits in intracellular trafficking in persistent stuttering. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

SU-G-JeP4-12: Real-Time Organ Motion Monitoring Using Ultrasound and KV Fluoroscopy During Lung SBRT Delivery

International Nuclear Information System (INIS)

Omari, E; Tai, A; Li, X; Cooper, D; Lachaine, M

2016-01-01

Purpose: Real-time ultrasound monitoring during SBRT is advantageous in understanding and identifying motion irregularities which may cause geometric misses. In this work, we propose to utilize real-time ultrasound to track the diaphragm in conjunction with periodical kV fluoroscopy to monitor motion of tumor or landmarks during SBRT delivery. Methods: Transabdominal Ultrasound (TAUS) b-mode images were collected from 10 healthy volunteers using the Clarity Autoscan System (Elekta). The autoscan transducer, which has a center frequency of 5 MHz, was utilized for the scans. The acquired images were contoured using the Clarity Automatic Fusion and Contouring workstation software. Monitoring sessions of 5 minute length were observed and recorded. The position correlation between tumor and diaphragm could be established with periodic kV fluoroscopy periodically acquired during treatment with Elekta XVI. We acquired data using a tissue mimicking ultrasound phantom with embedded spheres placed on a motion stand using ultrasound and kV Fluoroscopy. MIM software was utilized for image fusion. Correlation of diaphragm and target motion was also validated using 4D-MRI and 4D-CBCT. Results: The diaphragm was visualized as a hyperechoic region on the TAUS b-mode images. Volunteer set-up can be adjusted such that TAUS probe will not interfere with treatment beams. A segment of the diaphragm was contoured and selected as our tracking structure. Successful monitoring sessions of the diaphragm were recorded. For some volunteers, diaphragm motion over 2 times larger than the initial motion has been observed during tracking. For the phantom study, we were able to register the 2D kV Fluoroscopy with the US images for position comparison. Conclusion: We demonstrated the feasibility of tracking the diaphragm using real-time ultrasound. Real-time tracking can help in identifying such irregularities in the respiratory motion which is correlated to tumor motion. We also showed the

Development of 66 kV/6.9 kV 2 MV A prototype HTS power transformer

International Nuclear Information System (INIS)

Bohno, T.; Tomioka, A.; Imaizumi, M.; Sanuki, Y.; Yamamoto, T.; Yasukawa, Y.; Ono, H.; Yagi, Y.; Iwadate, K.

2005-01-01

We have developed the technology of the producing a HTS magnet for the power transformer. Three subjects have been mainly studied, high voltage technologies, large current and low AC loss technologies and sub-cooling system technologies to establish the technology of 66 kV/6.9 kV 10 MV A class HTS power transformer. In order to verify the validity of elemental technologies, such as high voltage technologies, large current and low AC loss technologies and sub-cooling system technologies, single-phase 2 MV A class 66 kV/6.9 kV prototype HTS transformer was manufactured and tested. In the load loss (AC loss) measurement, it was obtained that the measured value of 633 W was almost corresponding to the calculated value of 576 W at the rated operation of 2 MV A. Moreover, the breakdown was not found all voltage withstand test. These test results indicate that elemental technologies were established for the development of 66 kV/6.9 kV 10 MV A class HTS power transformer

Genome-Wide Analysis of the AP2/ERF Gene Family in Physic Nut and Overexpression of the JcERF011 Gene in Rice Increased Its Sensitivity to Salinity Stress.

Science.gov (United States)

Tang, Yuehui; Qin, Shanshan; Guo, Yali; Chen, Yanbo; Wu, Pingzhi; Chen, Yaping; Li, Meiru; Jiang, Huawu; Wu, Guojiang

2016-01-01

The AP2/ERF transcription factors play crucial roles in plant growth, development and responses to biotic and abiotic stresses. A total of 119 AP2/ERF genes (JcAP2/ERFs) have been identified in the physic nut genome; they include 16 AP2, 4 RAV, 1 Soloist, and 98 ERF genes. Phylogenetic analysis indicated that physic nut AP2 genes could be divided into 3 subgroups, while ERF genes could be classed into 11 groups or 43 subgroups. The AP2/ERF genes are non-randomly distributed across the 11 linkage groups of the physic nut genome and retain many duplicates which arose from ancient duplication events. The expression patterns of several JcAP2/ERF duplicates in the physic nut showed differences among four tissues (root, stem, leaf, and seed), and 38 JcAP2/ERF genes responded to at least one abiotic stressor (drought, salinity, phosphate starvation, and nitrogen starvation) in leaves and/or roots according to analysis of digital gene expression tag data. The expression of JcERF011 was downregulated by salinity stress in physic nut roots. Overexpression of the JcERF011 gene in rice plants increased its sensitivity to salinity stress. The increased expression levels of several salt tolerance-related genes were impaired in the JcERF011-overexpressing plants under salinity stress.

Uncoupling PIP2-calmodulin regulation of Kv7.2 channels by an assembly destabilizing epileptogenic mutation.

Science.gov (United States)

Alberdi, Araitz; Gomis-Perez, Carolina; Bernardo-Seisdedos, Ganeko; Alaimo, Alessandro; Malo, Covadonga; Aldaregia, Juncal; Lopez-Robles, Carlos; Areso, Pilar; Butz, Elisabeth; Wahl-Schott, Christian; Villarroel, Alvaro

2015-11-01

We show that the combination of an intracellular bi-partite calmodulin (CaM)-binding site and a distant assembly region affect how an ion channel is regulated by a membrane lipid. Our data reveal that regulation by phosphatidylinositol(4,5)bisphosphate (PIP2) and stabilization of assembled Kv7.2 subunits by intracellular coiled-coil regions far from the membrane are coupled molecular processes. Live-cell fluorescence energy transfer measurements and direct binding studies indicate that remote coiled-coil formation creates conditions for different CaM interaction modes, each conferring different PIP2 dependency to Kv7.2 channels. Disruption of coiled-coil formation by epilepsy-causing mutation decreases apparent CaM-binding affinity and interrupts CaM influence on PIP2 sensitivity. © 2015. Published by The Company of Biologists Ltd.

The mechanisms of action of E. coli endonuclease III and T4 UV endonuclease (endonuclease V) at AP sites.

OpenAIRE

Kim, J; Linn, S

1988-01-01

Treatment of DNA containing AP sites with either T4 UV endonuclease or with E. coli endonuclease III followed by a human class II AP endonuclease releases a putative beta-elimination product. This result suggests that both the T4 endonuclease and E. coli endonuclease III class I AP endonucleases catalyze phosphodiester bond cleavage via a lyase- rather than a hydrolase mechanism. Indeed, we have not detected a class I AP endonuclease which hydrolytically catalyzes phosphodiester bond cleavage...

From pan-reactive KV7 channel opener to subtype selective opener/inhibitor by addition of a methyl group.

Directory of Open Access Journals (Sweden)

Sigrid Marie Blom

Full Text Available The voltage-gated potassium channels of the KV7 family (KV7.1-5 play important roles in controlling neuronal excitability and are therefore attractive targets for treatment of CNS disorders linked to hyperexcitability. One of the main challenges in developing KV7 channel active drugs has been to identify compounds capable of discriminating between the neuronally expressed subtypes (KV7.2-5, aiding the identification of the subunit composition of KV7 currents in various tissues, and possessing better therapeutic potential for particular indications. By taking advantage of the structure-activity relationship of acrylamide KV7 channel openers and the effects of these compounds on mutant KV7 channels, we have designed and synthesized a novel KV7 channel modulator with a unique profile. The compound, named SMB-1, is an inhibitor of KV7.2 and an activator of KV7.4. SMB-1 inhibits KV7.2 by reducing the current amplitude and increasing the time constant for the slow component of the activation kinetics. The activation of KV7.4 is seen as an increase in the current amplitude and a slowing of the deactivation kinetics. Experiments studying mutant channels with a compromised binding site for the KV7.2-5 opener retigabine indicate that SMB-1 binds within the same pocket as retigabine for both inhibition of KV7.2 and activation of KV7.4. SMB-1 may serve as a valuable tool for KV7 channel research and may be used as a template for further design of better subtype selective KV7 channel modulators. A compound with this profile could hold novel therapeutic potential such as the treatment of both positive and cognitive symptoms in schizophrenia.

Effects of the small molecule HERG activator NS1643 on Kv11.3 channels.

Directory of Open Access Journals (Sweden)

Arne Bilet

Full Text Available NS1643 is one of the small molecule HERG (Kv11.1 channel activators and has also been found to increase erg2 (Kv11.2 currents. We now investigated whether NS1643 is also able to act as an activator of Kv11.3 (erg3 channels expressed in CHO cells. Activation of rat Kv11.3 current occurred in a dose-dependent manner and maximal current increasing effects were obtained with 10 µM NS1643. At this concentration, steady-state outward current increased by about 80% and the current increase was associated with a significant shift in the voltage dependence of activation to more negative potentials by about 15 mV. In addition, activation kinetics were accelerated, whereas deactivation was slowed. There was no significant effect on the kinetics of inactivation and recovery from inactivation. The strong current-activating agonistic effect of NS1643 did not result from a shift in the voltage dependence of Kv11.3 channel inactivation and was independent from external Na(+ or Ca(2+. At the higher concentration of 20 µM, NS1643 induced clearly less current increase. The left shift in the voltage dependence of activation reversed and the voltage sensitivity of activation dramatically decreased along with a slowing of Kv11.3 channel activation. These data show that, in comparison to other Kv11 family members, NS1643 exerts distinct effects on Kv11.3 channels with especially pronounced partial antagonistic effects at higher concentration.

Void coefficient of reactivity calculation for AP-600 core

International Nuclear Information System (INIS)

Suparlina, L.; Budiono, T.A.; Mardha, A.; Tukiran

1998-01-01

Void coefficient of reactivity as one of reactor kinetics parameters has been carried out. The calculation was done into two steps which is cell calculation using WIMSD/4 and core calculation using Batan-2DIFF code programs with the condition of beginning of cycle with all fresh fuels elements and all control rods withdrawn. The one dimension transport program in four neutron energy groups is used to calculate the cell generation of various core materials cell has been calculated in 1/4 fuel element with cluster model and square pitch arrange. Moderator density have been reduced until 20% for the void coefficient of reactivity calculation. Macroscopic cross-section as the out put of WIMSD/4 is being used as the input at the diffusion neutron program for core calculation. The void coefficient of reactivity of the AP-600 core can be determined with regular neutron flux and adjoint in four energy groups and X-Y geometry. The results is shown that the K eff calculation value is different 5.2% from the design data

T Cell Subset and Stimulation Strength-Dependent Modulation of T Cell Activation by Kv1.3 Blockers.

Directory of Open Access Journals (Sweden)

Wai-Ping Fung-Leung

Full Text Available Kv1.3 is a voltage-gated potassium channel expressed on T cells that plays an important role in T cell activation. Previous studies have shown that blocking Kv1.3 channels in human T cells during activation results in reduced calcium entry, cytokine production, and proliferation. The aim of the present study was to further explore the effects of Kv1.3 blockers on the response of different human T cell subsets under various stimulation conditions. Our studies show that, unlike the immune suppressor cyclosporine A, the inhibitory effect of Kv1.3 blockers was partial and stimulation strength dependent, with reduced inhibitory efficacy on T cells under strengthened anti-CD3/CD28 stimulations. T cell responses to allergens including house dust mites and ragweed were partially reduced by Kv1.3 blockers. The effect of Kv1.3 inhibition was dependent on T cell subsets, with stronger effects on CCR7- effector memory compared to CCR7+ central memory CD4 T cells. Calcium entry studies also revealed a population of CD4 T cells resistant to Kv1.3 blockade. Activation of CD4 T cells was accompanied with an increase in Kv1.3 currents but Kv1.3 transcripts were found to be reduced, suggesting a posttranscriptional mechanism in the regulation of Kv1.3 activities. In summary, Kv1.3 blockers inhibit T cell activation in a manner that is highly dependent on the T cell identity and stimulation strength, These findings suggest that Kv1.3 blockers inhibit T cells in a unique, conditional manner, further refining our understanding of the therapeutic potential of Kv1.3 blockers.

Ap/sub 4/A interactions with a multiprotein form of DNA polymerase. cap alpha. - primase from HeLa cells

Energy Technology Data Exchange (ETDEWEB)

Baril, E F; Owen, M W; Vishwanatha, J K; Zamecnik, P C

1984-06-01

In previous studies, it was shown that Ap/sub 4/A can function as a primer for in vitro DNA synthesis by the multiprotein form of DNA polymerase ..cap alpha.. with single-stranded DNA and an octadecamer double-stranded DNA template. In these studies, the authors show that Ap/sub 4/A that is greater than 99% pure by high performance liquid chromatography also stimulates the incorporation of (..cap alpha../sup 32/P)ATP into the 10-15 oligoribonucleotide primer with poly(dT) template by the primase that is resolved from the polymerase ..cap alpha.. core enzyme. Other dinucleotides or dinucleotide polyphosphates (e.g. ApA, Ap/sub 2/A or Ap/sub 3/A) do not enhance the incorporation of (..cap alpha../sup 32/P)ATP in this reaction. The results from phosphate transfer experiments demonstrate a covalent linkage between (/sup 3/H)Ap/sub 4/A and the /sup 32/P-labeled oligoriboadenylate that is synthesized by the primase.

SU-E-T-163: Thin-Film Organic Photocell (OPV) Properties in MV and KV Beams for Dosimetry Applications.

Science.gov (United States)

Ng, S K; Hesser, J; Zhang, H; Gowrisanker, S; Yakushevich, S; Shulhevich, Y; Abkai, C; Wack, L; Zygmanski, P

2012-06-01

To characterize dosimetric properties of low-cost thin film organic-based photovoltaic (OPV) cells to kV and MV x-ray beams for their usage as large area dosimeter for QA and patient safety monitoring device. A series of thin film OPV cells of various areas and thicknesses were irradiated with MV beams to evaluate the stability and reproducibility of their response, linearity and sensitivity to absorbed dose. The OPV response to x-rays of various linac energies were also characterized. Furthermore the practical (clinical) sensitivity of the cells was determined using IMRT sweeping gap test generated with various gap sizes. To evaluate their potential usage in the development of low cost kV imaging device, the OPV cells were irradiated with kV beam (60-120 kVp) from a fluoroscopy unit. Photocell response to the absorbed dose was characterized as a function of the organic thin film thickness and size, beam energy and exposure for kV beams as well. In addition, photocell response was determined with and without thin plastic scintillator. Response of the OPV cells to the absorbed dose from kV and MV beams are stable and reproducible. The photocell response was linearly proportional to the size and about slightly decreasing with the thickness of the organic thin film, which agrees with the general performance of the photocells in visible light. The photocell response increases as a linear function of absorbed dose and x-ray energy. The sweeping gap tests performed showed that OPV cells have sufficient practical sensitivity to measured MV x-ray delivery with gap size as small as 1 mm. With proper calibration, the OPV cells could be used for online radiation dose measurement for quality assurance and patient safety purposes. Their response to kV beam show promising potential in development of low cost kV radiation detection devices. © 2012 American Association of Physicists in Medicine.

Macroscopic and radiographic examination of proximal root surface caries

International Nuclear Information System (INIS)

Nordenram, G.; Bergvist, A.; Johnson, G.; Henriksen, C.O.; Anneroth, G.

1988-01-01

The purpose of the study was to compare macroscopic and radiographic examination of proximal root surface caries of extracted teeth from patients aged 65-95 years. Although the study conditions for macroscopic and radiographic diagnosis favored more sensitive evaluations than routine clinical conditions, there was a 24% disagreement in diagnosis. This finding indicates that under routine clinical conditions it is difficult to register with certainty all superficial root carious lesions. Even in the absence of clinically detectable root surface caries, preventive measures should be considered for elderly people with exposed root surfaces

Development of 10 kV 4H-SiC JBS diode with FGR termination

International Nuclear Information System (INIS)

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

2014-01-01

The design, fabrication, and electrical characteristics of the 4H-SiC JBS diode with a breakdown voltage higher than 10 kV are presented. 60 floating guard rings have been used in the fabrication. Numerical simulations have been performed to select the doping level and thickness of the drift layer and the effectiveness of the edge termination technique. The n-type epilayer is 100 μm in thickness with a doping of 6 × 10 14 cm −3 . The on-state voltage was 2.7 V at J F = 13 A/cm 2 . (semiconductor devices)

Phospholipase C δ4 regulates cold sensitivity in mice.

Science.gov (United States)

Yudin, Yevgen; Lutz, Brianna; Tao, Yuan-Xiang; Rohacs, Tibor

2016-07-01

had more depolarized resting membrane potentials, and required smaller current injections to generate action potentials (APs) than medium-large cells. In small PLCδ4(-/-) neurons, menthol application induced larger depolarizations and generation of APs with frequencies significantly higher compared to WT neurons. In behavioural experiments PLCδ4(-/-) mice showed greater sensitivity to evaporative cooling by acetone than control animals. Pretreatment with the TRPM8 antagonist PBMC reduced cold-induced responses, and the effect was more pronounced in the PLCδ4(-/-) group. Heat and mechanical sensitivity of the PLCδ4(-/-) mice was not different from WT animals. Our data support the involvement of PLCδ4 in the regulation of TRPM8 channel activity in vivo. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Designed Er(3+)-singly doped NaYF4 with double excitation bands for simultaneous deep macroscopic and microscopic upconverting bioimaging.

Science.gov (United States)

Wen, Xuanyuan; Wang, Baoju; Wu, Ruitao; Li, Nana; He, Sailing; Zhan, Qiuqiang

2016-06-01

Simultaneous deep macroscopic imaging and microscopic imaging is in urgent demand, but is challenging to achieve experimentally due to the lack of proper fluorescent probes. Herein, we have designed and successfully synthesized simplex Er(3+)-doped upconversion nanoparticles (UCNPs) with double excitation bands for simultaneous deep macroscopic and microscopic imaging. The material structure and the excitation wavelength of Er(3+)-singly doped UCNPs were further optimized to enhance the upconversion emission efficiency. After optimization, we found that NaYF4:30%Er(3+)@NaYF4:2%Er(3+) could simultaneously achieve efficient two-photon excitation (2PE) macroscopic tissue imaging and three-photon excitation (3PE) deep microscopic when excited by 808 nm continuous wave (CW) and 1480 nm CW lasers, respectively. In vitro cell imaging and in vivo imaging have also been implemented to demonstrate the feasibility and potential of the proposed simplex Er(3+)-doped UCNPs as bioprobe.

The role of voltage-gated potassium channels in the regulation of mouse uterine contractility

Directory of Open Access Journals (Sweden)

Abel Peter W

2007-11-01

Full Text Available Abstract Background Uterine smooth muscle cells exhibit ionic currents that appear to be important in the control of uterine contractility, but how these currents might produce the changes in contractile activity seen in pregnant myometrium has not been established. There are conflicting reports concerning the role of voltage-gated potassium (Kv channels and large-conductance, calcium-activated potassium (BK channels in the regulation of uterine contractility. In this study we provide molecular and functional evidence for a role for Kv channels in the regulation of spontaneous contractile activity in mouse myometrium, and also demonstrate a change in Kv channel regulation of contractility in pregnant mouse myometrium. Methods Functional assays which evaluated the effects of channel blockers and various contractile agonists were accomplished by quantifying contractility of isolated uterine smooth muscle obtained from nonpregnant mice as well as mice at various stages of pregnancy. Expression of Kv channel proteins in isolated uterine smooth muscle was evaluated by Western blots. Results The Kv channel blocker 4-aminopyridine (4-AP caused contractions in nonpregnant mouse myometrium (EC50 = 54 micromolar, maximal effect at 300 micromolar but this effect disappeared in pregnant mice; similarly, the Kv4.2/Kv4.3 blocker phrixotoxin-2 caused contractions in nonpregnant, but not pregnant, myometrium. Contractile responses to 4-AP were not dependent upon nerves, as neither tetrodotoxin nor storage of tissues at room temperature significantly altered these responses, nor were responses dependent upon the presence of the endometrium. Spontaneous contractions and contractions in response to 4-AP did not appear to be mediated by BK, as the BK channel-selective blockers iberiotoxin, verruculogen, or tetraethylammonium failed to affect either spontaneous contractions or 4-AP-elicited responses. A number of different Kv channel alpha subunit proteins were

250 kV aim for hvdc valves

Energy Technology Data Exchange (ETDEWEB)

1966-06-01

Development now being carried out by ASEA is aimed at increasing the normal operating voltage for a mercury arc valve to 250 kV dc. The maximum direct voltage per valve group, with one valve in each arm of the bridge, is 125 kV for equipment already in operation in New Zealand, Japan, and Konti Scan. Valves for 130 kV and 133 kV operation are under construction for the Vancouver and the Pacific Intertie 1 links.

Cardiac Subtype-Specific Modeling of Kv1.5 Ion Channel Deficiency Using Human Pluripotent Stem Cells

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Maike Marczenke

2017-07-01

Full Text Available The ultrarapid delayed rectifier K+ current (IKur, mediated by Kv1.5 channels, constitutes a key component of the atrial action potential. Functional mutations in the underlying KCNA5 gene have been shown to cause hereditary forms of atrial fibrillation (AF. Here, we combine targeted genetic engineering with cardiac subtype-specific differentiation of human induced pluripotent stem cells (hiPSCs to explore the role of Kv1.5 in atrial hiPSC-cardiomyocytes. CRISPR/Cas9-mediated mutagenesis of integration-free hiPSCs was employed to generate a functional KCNA5 knockout. This model as well as isogenic wild-type control hiPSCs could selectively be differentiated into ventricular or atrial cardiomyocytes at high efficiency, based on the specific manipulation of retinoic acid signaling. Investigation of electrophysiological properties in Kv1.5-deficient cardiomyocytes compared to isogenic controls revealed a strictly atrial-specific disease phentoype, characterized by cardiac subtype-specific field and action potential prolongation and loss of 4-aminopyridine sensitivity. Atrial Kv1.5-deficient cardiomyocytes did not show signs of arrhythmia under adrenergic stress conditions or upon inhibiting additional types of K+ current. Exposure of bulk cultures to carbachol lowered beating frequencies and promoted chaotic spontaneous beating in a stochastic manner. Low-frequency, electrical stimulation in single cells caused atrial and mutant-specific early afterdepolarizations, linking the loss of KCNA5 function to a putative trigger mechanism in familial AF. These results clarify for the first time the role of Kv1.5 in atrial hiPSC-cardiomyocytes and demonstrate the feasibility of cardiac subtype-specific disease modeling using engineered hiPSCs.

Hvor fosser kvælstoffet hen?

DEFF Research Database (Denmark)

Larsen, Torben

Der har i Ingeniøren inden i et par måneder kunne læses adskillelige ivrige indlæg om de danske fjordes evne til at fjerne kvælstof. Kvælstof fosser ud af fjordene? lød en af de første overskrifter. Få uger efter blev det stik modsatte synspunkt fremført under overskriften Fjordene holder på kvæl...

SU-G-JeP4-13: Continuous Intra-Fractional Monitoring of the Prostate Using Dynamic KV Collimation and Tube Current Modulation

Energy Technology Data Exchange (ETDEWEB)

Parsons, D [Dalhousie Unviersity, Halifax, Nova Scotia (Canada); Robar, J [Dalhousie Unviersity, Halifax, Nova Scotia (Canada); Nova Scotia Health Authority, Halifax, NS (Canada)

2016-06-15

Purpose: The focus of this work is to improve the available kV image quality for continuous intra-fraction monitoring of the prostate. This is investigated using a novel blade collimation system enabling modulated volume-of-interest (VOI) imaging of prostate fiducial markers. Methods: A four-blade dynamic kV collimator was used to track a VOI during gantry rotation. Planar image quality was investigated as a function of collimator dimension, while maintaining the same dose to isocenter, for a 22.2 cm diameter cylindrical water phantom with a 9 mm diameter bone insert. A sample prostate anatomy was defined in the planning system, including three fiducial markers within the CTV. The VOI margin around each marker was set to be 2σ of the population covariance matrix characterizing prostate motion. DRRs were used to calculate the kV attenuation for each VOI as a function of angle. The optimal marker and tube current were determined using kV attenuation. Monte Carlo simulations were used to calculate the imaging dose to the phantom and MV scatter dose to the imaging panel. Results: Preliminary measurements show an increase in CNR by a factor of 1.3 with the VOI method, when decreasing from an 6×6 to 2×2 cm{sup 2} field. Attenuation calculations show a change in kV fluence at the detector by a factor of 21.6 with fiducial optimization; resultant tube current modulation increases maximum dose by a factor of 1.4 compared to no modulation. MV scatter contribution to the kV detector changes by approximately a factor of two over a complete gantry rotation. Conclusion: The dynamic collimation system allows single fiducial marker tracking at a very low dose, with reduction of scatter and improvement of image quality, compared to imaging the entire prostate. The approach is compatible with tube current modulation, which enables consistent image quality throughout the range of gantry rotation. This project was funded by Varian Medical Systems.

Diagnosis of bladder tumours in patients with macroscopic haematuria

DEFF Research Database (Denmark)

Gandrup, Karen L; Løgager, Vibeke B; Bretlau, Thomas

2015-01-01

patients underwent CTU, MRU and flexible cystoscopy. Two uroradiologists individually reviewed the images without any clinical information, using a questionnaire. Patient records and pathology reports were also reviewed. RESULTS: At flexible cystoscopy, MRU and CTU, 32, 19 and 15 bladder lesions were...... identified, respectively. Histopathology showed that 13 of the 29 biopsied lesions were transitional cell carcinomas. Compared with the histopathology, the sensitivity and specificity for detection of tumours by CTU and MRU were 61.5% and 94.9%, and 79.9% and 93.4%, respectively. False-positive detection...... of bladder tumours, compared with histopathology, was reported in seven CTUs and nine MRUs, whereas the number of false-negative findings was five for CTUs and three for MRUs. CONCLUSIONS: Split-bolus CTU or MRU cannot replace cystoscopy in cases of macroscopic haematuria. MRU has a higher sensitivity than...

Survey of magnetic fields near BPA 230-kV and 500-kV transmission lines

International Nuclear Information System (INIS)

Perrin, N.; Aggarwal, R.P.

1991-01-01

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

Molecular Expression and Pharmacological Evidence for a Functional Role of Kv7 Channel Subtypes in Guinea Pig Urinary Bladder Smooth Muscle

Science.gov (United States)

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. PMID:24073284

80 kV electrostatic wire septum for AmPS

International Nuclear Information System (INIS)

Linden, A. van der; Bijleveld, J.H.M.; Rookhuizen, H.B.; Bruinsma, P.J.T.; Heine, E.; Lassing, P.; Prins, E.

1992-01-01

The Amsterdam Pulse Stretcher (AmPS) ring aims at a 100% duty cycle operation by means of slow extraction of injected electron beam pulses of 2.1 μs. In the extraction process of the AmPS, the extracted beam is intercepted from the circulating beam by the 1 m long electrostatic wire septum. For a bending angle of 4.4 mrad the maximum anode voltage is 80 kV. Care has been given to the electric field distribution at the entrance and exit of the septum and to the insulators, required to support the anode. Prototype tests have been successful up to an anode voltage of 120 kV. (R.P.) 9 refs.; 5 figs

Center for Geometrisk Metrologi CGM ApS, Årsberetning 2001 til DANAK

DEFF Research Database (Denmark)

De Chiffre, Leonardo

Denne årsberetning omfatter CGM ApS' akkrediterede virksomhed i kalenderåret 2001. Årsberetningen er udarbejdet til DANAK (Dansk Akkreditering, Erhvervsfremme Styrelsen), som led i opfyldelsen af laboratoriets informationspligt i henhold til gældende regler (Teknisk Forskrift Nr. TF4 af 2000...

A Macroscopic Performance Analysis of NASA’s Northrop Grumman RQ-4A

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Enric Pastor

2018-01-01

Full Text Available This paper presents the process of identification, from a macroscopic point of view, of the Northrop Grumman RQ-4A Global Hawk Remote-Piloted Aircraft System from real, but limited flight information. Performance parameters and operational schemes will be extracted by analyzing available data from two specific science flights flown by the Global Hawk back in 2010. Each phase of the flight, take-off, climb, cruise climb, descent and landing, is analyzed from various points of view: speed profile, altitude, climb/descent ratios and rate of turn. The key performance parameters derived from individual flights will be confirmed by performing a wider statistical validation with additional flight trajectories. Derived data are exploited to validate a simulated RQ-4A vehicle employed in extensive real-time air traffic management simulated integration exercises and to complement the development of a future RQ-4A trajectory predictor.

Functional properties of human neuronal Kv11 channels

DEFF Research Database (Denmark)

Einarsen, Karoline; Calloe, Kirstine; Grunnet, Morten

2009-01-01

Kv11 potassium channels are important for regulation of the membrane potential. Kv11.2 and Kv11.3 are primarily found in the nervous system, where they most likely are involved in the regulation of neuronal excitability. Two isoforms of human Kv11.2 have been published so far. Here, we present...... current characteristics of the isoforms presented in this work may contribute to the regulation of neuronal excitability....

Functional and Molecular Evidence for Kv7 Channel Subtypes in Human Detrusor from Patients with and without Bladder Outflow Obstruction

DEFF Research Database (Denmark)

Svalø, Julie; Sheykhzade, Majid; Nordling, Jørgen

2015-01-01

The aim of the study was to investigate whether Kv7 channels and their ancillary β-subunits, KCNE, are functionally expressed in the human urinary bladder. Kv7 channels were examined at the molecular level and by functional studies using RT-qPCR and myography, respectively. We found mRNA expressi...... between Kv7 channels and β-adrenoceptors in the human urinary bladder. The performed gene expression analysis combined with the organ bath studies imply that compounds that activate Kv7 channels could be useful for treatment of overactive bladder syndrome.......The aim of the study was to investigate whether Kv7 channels and their ancillary β-subunits, KCNE, are functionally expressed in the human urinary bladder. Kv7 channels were examined at the molecular level and by functional studies using RT-qPCR and myography, respectively. We found mRNA expression...... (activator of Kv7.1 channels, 10 μM) and ML213 (activator of Kv7.2, Kv7.4, Kv7.4/7.5 and Kv7.5 channels, 10 μM), reduced the tone of 1 μM carbachol pre-constricted bladder strips. XE991 (blocker of Kv7.1-7.5 channels, 10 μM) had opposing effects as it increased contractions achieved with 20 mM KPSS...

Clinical manifestations of antiphospholipid syndrome (APS) with and without antiphospholipid antibodies (the so-called 'seronegative APS').

Science.gov (United States)

Rodriguez-Garcia, Jose Luis; Bertolaccini, Maria Laura; Cuadrado, Maria Jose; Sanna, Giovanni; Ateka-Barrutia, Oier; Khamashta, Munther A

2012-02-01

Although the medical literature currently provides a growing number of isolated case reports of patients with clinically well-defined antiphospholipid syndrome (APS) and persistently negative antiphospholipid antibodies (aPL), there are no studies including a series of patients addressing the clinical features of this condition. The authors assessed clinical manifestations of APS in 154 patients: 87 patients with seropositive APS and 67 patients with thrombosis and/or pregnancy morbidity persistently negative for aPL and presenting with at least two additional non-criteria manifestations of APS (the so-called 'seronegative APS', SN-APS). Patients were interviewed at the time of recruitment, and a retrospective file review was carried out. There were no significant differences in the frequency of thrombotic events or obstetric morbidity in patients with SN-APS versus patients with seropositive APS: deep vein thrombosis (31.4% vs 31.0%), pulmonary embolism (23.8% vs 28.7%), stroke (14.9% vs 17.2%), transient ischaemic attack (11.9% vs 10.3%), early spontaneous abortions (67.1% vs 52.1%), stillbirths (62.5% vs 59.4%), prematurity (28.1% vs 21.7%) or pre-eclampsia (28.1% vs 23.1%). Classic and SN-APS patients show similar clinical profiles. The results suggest that clinical management in patients with APS should not be based only on the presence of conventional aPL.

SGK3 Sensitivity of Voltage Gated K+ Channel Kv1.5 (KCNA5

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Musaab Ahmed

2016-01-01

Full Text Available Background: The serum & glucocorticoid inducible kinase isoform SGK3 is a powerful regulator of several transporters, ion channels and the Na+/K+ ATPase. Targets of SGK3 include the ubiquitin ligase Nedd4-2, which is in turn a known regulator of the voltage gated K+ channel Kv1.5 (KCNA5. The present study thus explored whether SGK3 modifies the activity of the voltage gated K+ channel KCNA5, which participates in the regulation of diverse functions including atrial cardiac action potential, activity of vascular smooth muscle cells, insulin release and tumour cell proliferation. Methods: cRNA encoding KCNA5 was injected into Xenopus oocytes with and without additional injection of cRNA encoding wild-type SGK3, constitutively active S419DSGK3, inactive K191NSGK3 and/or wild type Nedd4-2. Voltage gated K+ channel activity was quantified utilizing dual electrode voltage clamp. Results: Voltage gated current in KCNA5 expressing Xenopus oocytes was significantly enhanced by wild-type SGK3 and S419DSGK3, but not by K191NSGK3. SGK3 was effective in the presence of ouabain (1 mM and thus did not require Na+/K+ ATPase activity. Coexpression of Nedd4-2 decreased the voltage gated current in KCNA5 expressing Xenopus oocytes, an effect largely reversed by additional coexpression of SGK3. Conclusion: SGK3 is a positive regulator of KCNA5, which is at least partially effective by abrogating the effect of Nedd4-2.

Antiphospholipid syndrome (APS) nephropathy in catastrophic, primary, and systemic lupus erythematosus-related APS.

Science.gov (United States)

Tektonidou, Maria G; Sotsiou, Flora; Moutsopoulos, Haralampos M

2008-10-01

Renal involvement in antiphospholipid syndrome (APS) has been poorly recognized. A renal small-vessel vasculopathy, defined as APS nephropathy, has recently been observed in small series of patients with primary APS (PAPS) and systemic lupus erythematosus (SLE)-APS. We examined the renal histologic, clinical, and laboratory characteristics of different groups of patients with APS including catastrophic APS (CAPS). Our study included all CAPS (n=6), PAPS (n=8), and SLE-APS (n=23) patients with biopsy-proven renal involvement who were referred to our departments. The kidney biopsy specimens were retrospectively examined by the same renal pathologist. APS nephropathy was diagnosed as previously described. Demographic, clinical, and laboratory data were recorded. All patients with CAPS had acute and chronic renal vascular lesions compatible with diagnosis of APS nephropathy. Thrombotic microangiopathy (TMA), the acute lesion, was observed in all CAPS patients. Fibrous intimal hyperplasia of interlobular arteries (FIH) and focal cortical atrophy (FCA) were the most common chronic vascular lesions, occurring in 4 of 6 (66.7%) and 3 of 6 (50%) patients with CAPS, respectively. TMA was detected in 3 of 8 (37.5%) patients with PAPS and in 8 of 23 (35%) patients with SLE-APS, while FIH and FCA were found with similar frequencies in all 3 groups. Hypertension, proteinuria, hematuria, and renal insufficiency were the most common renal manifestations of all APS groups. Acute and chronic APS nephropathy lesions were detected in all 3 APS groups. Acute lesions were more prominent in CAPS, while chronic lesions were found with similar frequencies in all groups. Hypertension, proteinuria, hematuria, and renal insufficiency were the most common renal manifestations of all APS groups.

A 2-deoxyribonolactone-containing nucleotide: Isolation and characterization of the alkali-sensitive photoproduct of the trideoxyribonucleotide d(ApCpA)

International Nuclear Information System (INIS)

Urata, H.; Yamamoto, K.; Akagi, M.; Hiroaki, H.; Uesugi, S.

1989-01-01

It has been reported that ACA sequences in DNA are mutagenic hot spots in UV-induced mutagenesis and are sites of an alkali-sensitive lesion produced by UV irradiation. In order to characterize the UV-induced lesion of an ACA site, chemically synthesized trideoxyribonucleotide d(ApCpA) was irradiated with UV light and the alkali-sensitive photoproduct was isolated. The structure of this photoproduct was characterized as the trinucleotide containing 2-deoxyribonolactone at the internal residue by 2D DQF-COSY, FT-IR, FAB-MS, and chemical properties. It is known that this lesion is also produced by gamma-irradiation, neocarzinostatin, the 1,10-phenanthroline-copper complex, and hydrogen peroxide and is highly mutagenic because of its resistance to cleavage by certain apurinic/apyrimidinic (AP) endonucleases. Thus, 2-deoxyribonolactone may be one of the lethal DNA lesions induced by UV irradiation to organisms and one of the intermediates of UV-induced DNA strand breaks because the DNA strand is cleaved at this site with beta- and subsequent delta-elimination mechanisms

Kv7 channels can function without constitutive calmodulin tethering.

Directory of Open Access Journals (Sweden)

Juan Camilo Gómez-Posada

Full Text Available 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.

The pan-Kv7 (KCNQ) Channel Opener Retigabine Inhibits Striatal Excitability by Direct Action on Striatal Neurons In Vivo

DEFF Research Database (Denmark)

Hansen, Henrik H; Weikop, Pia; Mikkelsen, Maria D

2017-01-01

Central Kv7 (KCNQ) channels are voltage-dependent potassium channels composed of different combinations of four Kv7 subunits, being differently expressed in the brain. Notably, striatal dopaminergic neurotransmission is strongly suppressed by systemic administration of the pan-Kv7 channel opener ...... by acute systemic haloperidol administration in the rat. The relative mRNA levels of Kv7 subunits in the rat striatum were found to be Kv7.2 = Kv7.3 = Kv7.5 > >Kv7.4. These data suggest that intrastriatal Kv7 channels play a direct role in regulating striatal excitability in vivo....

Genotype-phenotype correlations and expansion of the molecular spectrum of AP4M1-related hereditary spastic paraplegia

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Conceição Bettencourt

2017-11-01

Full Text Available Abstract Background Autosomal recessive hereditary spastic paraplegia (HSP due to AP4M1 mutations is a very rare neurodevelopmental disorder reported for only a few patients. Methods We investigated a Greek HSP family using whole exome sequencing (WES. Results A novel AP4M1A frameshift insertion, and a very rare missense variant were identified in all three affected siblings in the compound heterozygous state (p.V174fs and p.C319R; the unaffected parents were carriers of only one variant. Patients were affected with a combination of: (a febrile seizures with onset in the first year of life (followed by epileptic non-febrile seizures; (b distinctive facial appearance (e.g., coarse features, bulbous nose and hypomimia; (c developmental delay and intellectual disability; (d early-onset spastic weakness of the lower limbs; and (e cerebellar hypoplasia/atrophy on brain MRI. Conclusions We review genotype-phenotype correlations and discuss clinical overlaps between different AP4-related diseases. The AP4M1 belongs to a complex that mediates vesicle trafficking of glutamate receptors, being likely involved in brain development and neurotransmission.

Results of the AP600 advanced plant probabilistic risk assessment

International Nuclear Information System (INIS)

Bueter, T.; Sancaktar, S.; Freeland, J.

1997-01-01

The AP600 Probabilistic Risk Assessment (PRA) includes detailed models of the plant systems, including the containment and containment systems that would be used to mitigate the consequences of a severe accident. The AP600 PRA includes a level 1 analysis (core damage frequency), and a level 2 analysis (environmental consequences), an assessment of the plant vulnerability to accidents caused by fire or floods, and a seismic margins analysis. Numerous sensitivities are included in the AP600 PRA including one that assumes no credit for non-safety plant systems. The core damage frequency for the AP600 of 1.7E-07/year is small compared with other PRAs performed in the nuclear industry. The AP600 large release frequency of 1.8E-08/year is also small and shows the ability of the containment systems to prevent a large release should a severe accident occur. Analyses of potential consequences to the environment from a severe accident show that a release would be small, and that containment still provides significant protection 24 hours after an assumed accident. Sensitivity analyses show that plant risk (as measured by core damage frequency and large release frequency) is not sensitive to the reliability of operator actions. 6 refs., 1 fig., 1 tab

The C-terminal HRET sequence of Kv1.3 regulates gating rather than targeting of Kv1.3 to the plasma membrane.

Science.gov (United States)

Voros, Orsolya; Szilagyi, Orsolya; Balajthy, András; Somodi, Sándor; Panyi, Gyorgy; Hajdu, Péter

2018-04-12

Kv1.3 channels are expressed in several cell types including immune cells, such as T lymphocytes. The targeting of Kv1.3 to the plasma membrane is essential for T cell clonal expansion and assumed to be guided by the C-terminus of the channel. Using two point mutants of Kv1.3 with remarkably different features compared to the wild-type Kv1.3 (A413V and H399K having fast inactivation kinetics and tetraethylammonium-insensitivity, respectively) we showed that both Kv1.3 channel variants target to the membrane when the C-terminus was truncated right after the conserved HRET sequence and produce currents identical to those with a full-length C-terminus. The truncation before the HRET sequence (NOHRET channels) resulted in reduced membrane-targeting but non-functional phenotypes. NOHRET channels did not display gating currents, and coexpression with wild-type Kv1.3 did not rescue the NOHRET-A413V phenotype, no heteromeric current was observed. Interestingly, mutants of wild-type Kv1.3 lacking HRET(E) (deletion) or substituted with five alanines for the HRET(E) motif expressed current indistinguishable from the wild-type. These results demonstrate that the C-terminal region of Kv1.3 immediately proximal to the S6 helix is required for the activation gating and conduction, whereas the presence of the distal region of the C-terminus is not exclusively required for trafficking of Kv1.3 to the plasma membrane.

Radiation dose reduction sinogram affirmed iterative reconstruction and automatic tube voltage modulation(CARE kV) in abdominal CT

International Nuclear Information System (INIS)

Shin, Hyun Joo; Chung, Yong Eun; Lee, Young Han; Choi, Jin Young; Park, Mi Suk; Kim, Myeong Jin; Kim, Ki Whang

2013-01-01

To evaluate the feasibility of sinogram-affirmed iterative reconstruction (SAFIRE) and automated kV modulation (CARE kV) in reducing radiation dose without increasing image noise for abdominal CT examination. This retrospective study included 77 patients who received CT imaging with an application of CARE kV with or without SAFIRE and who had comparable previous CT images obtained without CARE kV or SAFIRE, using the standard dose (i.e., reference mAs of 240) on an identical CT scanner and reconstructed with filtered back projection (FBP) within 1 year. Patients were divided into two groups: group A (33 patients, CT scanned with CARE kV); and group B (44 patients, scanned after reducing the reference mAs from 240 to 170 and applying both CARE kV and SAFIRE). CT number, image noise for four organs and radiation dose were compared among the two groups. Image noise increased after CARE kV application (p < 0.001) and significantly decreased as SAFIRE strength increased (p < 0.001). Image noise with reduced-mAs scan (170 mAs) in group B became similar to that of standard-dose FBP images after applying CARE kV and SAFIRE strengths of 3 or 4 when measured in the aorta, liver or muscle (p ≥ 0.108). Effective doses decreased by 19.4% and 41.3% for groups A and B, respectively (all, p < 0.001) after application of CARE kV with or without SAFIRE. Combining CARE kV, reduction of mAs from 240 to 170 mAs and noise reduction by applying SAFIRE strength 3 or 4 reduced the radiation dose by 41.3% without increasing image noise compared with the standard-dose FBP images.

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

International Nuclear Information System (INIS)

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

2008-01-01

Voltage-dependent K + 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 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

High power cable with internal water cooling 400 kV

Energy Technology Data Exchange (ETDEWEB)

Rasquin, W; Harjes, B

1982-08-01

The project was planned for a duration of 4 years. Afterwards it has been extended over 6 years and finally stopped after 3 1/2 years. Therefore, of course results of field tests with an internally cooled 400 kV cable are not available. Nevertheless, this conductor cooled high power cable has been developed to such an extend, that this manufactured cable could withstand type tests according to IEC/VDE recommendations. Even by missing field tests it is obvious that a high power cable for 400 kV is available.

Task Force on Catastrophic Antiphospholipid Syndrome (APS) and Non-criteria APS Manifestations (I): catastrophic APS, APS nephropathy and heart valve lesions.

Science.gov (United States)

Cervera, R; Tektonidou, M G; Espinosa, G; Cabral, A R; González, E B; Erkan, D; Vadya, S; Adrogué, H E; Solomon, M; Zandman-Goddard, G; Shoenfeld, Y

2011-02-01

The objectives of the 'Task Force on Catastrophic Antiphospholipid Syndrome (APS) and Non-criteria APS Manifestations' were to assess the clinical utility of the international consensus statement on classification criteria and treatment guidelines for the catastrophic APS, to identify and grade the studies that analyse the relationship between the antiphospholipid antibodies and the non-criteria APS manifestations and to present the current evidence regarding the accuracy of these non-criteria APS manifestations for the detection of patients with APS. This article summarizes the studies analysed on the catastrophic APS, APS nephropathy and heart valve lesions, and presents the recommendations elaborated by the Task Force after this analysis.

Experimental research of liquid entrainment through ADS-4 in AP1000

International Nuclear Information System (INIS)

Meng, Zhaoming; Dong, Bo; Wang, Laishun; Fu, Xiaoliang; Tian, Wenxi; Yang, Yanhua; Su, Guanghui

2014-01-01

Highlights: • We performed experimental research of liquid entrainment through ADS-4 in AP1000. • Effect of various factors on entrainment at T-junction was conducted. • Visualization research was conducted to make entrainment mechanism clear. - Abstract: In this study, based on a T-junction that consists of Automatic Depressurization System Stage Four (ADS-4) and hot leg in an AP1000 plant, a small-scale experimental research on entrainment at a T-junction was performed. This study mainly focused on the effect of various factors on entrainment, such as the effect of branch size, branch shape and liquid crossflow. The flow pattern map was plotted from the experimental data, and the visualization research indicated that the entrainment phenomena through a large size branch were apparently different from that through a small branch. Three entrainment phenomena were observed in the studies, two entrainment mechanisms could be found in the stratified flow regime entrainment area, the existence of branch contributed to generating intermittent flow in the horizontal main pipe, and the backflow region was observable in the vicinity of a large size branch inlet. Also, experimental research showed that downstream of the branch of T-junction had an important effect on the onset entrainment, and liquid crossflow did not seem to affect the onset entrainment

The short-circuit test results of 6.9 kV/2.3 kV 400 kVA-class YBCO model transformer

International Nuclear Information System (INIS)

Tomioka, A.; Otonari, T.; Ogata, T.; Iwakuma, M.; Okamoto, H.; Hayashi, H.; Iijima, Y.; Saito, T.; Gosho, Y.; Tanabe, K.; Izumi, T.; Shiohara, Y.

2011-01-01

The 6.9 kV/2.3 kV 400 kVA-class single-phase YBCO model transformer with the YBCO tape with copper tape was manufactured for short-circuit current test. Short-circuit test was performed and the short-circuit current of primary winding was 346 A which was about six times larger than the rated current. The I-V characteristics of the winding did not change before and after the test. The transformer withstood short-circuit current. We are planning to turn the result into a consideration of a 66 kV/6.9 kV-20 MVA-class three-phase superconducting transformer. We are developing an elemental technology for 66 kV/6.9 kV 20 MVA-class power transformer with YBCO conductors. The protection of short-circuit technology is one of the elemental technologies for HTS transformer. Since short-circuit current is much higher than critical current of YBCO tape, there is a possibility that superconducting characteristics may be damaged during short-circuit period. We made a conductor to compose the YBCO tape with copper tape. We manufactured 6.9 kV/2.3 kV 400 kVA-class YBCO model transformer using this conductor and performed short-circuit current test. The short-circuit current of primary winding was 346 A which was about six times larger than the rated current. The I-V characteristics of the winding did not change before and after the test. We may consider this conductor withstands short-circuit current.

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

Energy Technology Data Exchange (ETDEWEB)

Ma, Zhan-Wen; Su, Xiao-Dong; Wei, Zhen; Huang, Zhi-Wu; Miao, Tian-You; Su, Tong-Ling [School of Nuclear Science and Technology, Lanzhou University, Lanzhou 730000 (China); Lu, Xiao-Long; Wang, Jun-Run; Yao, Ze-En, E-mail: zeyao@lzu.edu.cn [School of Nuclear Science and Technology, Lanzhou University, Lanzhou 730000 (China); Engineering Research Center for Neutron Application, Ministry of Education, Lanzhou University, Lanzhou 730000 (China)

2016-08-15

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%.

X irradiation of human epidermis in vitro. 2. Comparison of single 44 kV and 200 kV X irradiation

Energy Technology Data Exchange (ETDEWEB)

Wollina, U; Fueller, J; Burger, B; Hipler, C

1989-01-01

On the example of the reduction of epidermal adhesion of FITC wheat germ agglutinine (WGA) the direct membrane effect of a single X irradiation (44 kV and 220 kV) was analyzed in vitro. Human normal skin and psoriasis centres were compared. Normal skin showed no alteration of microscopically visible FITC-WGA adhesion on epidermal cells over the whole dose range. Foci of psoriasis responded to doses of /ge/ 5 Gy (44 and 220 kV) with a drastic reduction of epidermal lectin binding to lower and medium cell layers. Maximum efficacy was with 5 Gy (44 kV) or 10 Gy (220 kV). A dose elevation up to 20 Gy did not result in an increase of efficacy. Topographically the radiosensitive FITC-WGA adhesion could chiefly be seen in the dermal ridges. The findings support the impression of an increased radiosensitivity of the lesional psoriatic epidermis compared with normal skin. This is connected with an abnormal differentiation of keratinocytes in psoriasis. (author).

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

Directory of Open Access Journals (Sweden)

Michael W. Pennington

2015-01-01

Full Text Available 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.

Real-time estimation of prostate tumor rotation and translation with a kV imaging system based on an iterative closest point algorithm

International Nuclear Information System (INIS)

Tehrani, Joubin Nasehi; O’Brien, Ricky T; Keall, Paul; Poulsen, Per Rugaard

2013-01-01

Previous studies have shown that during cancer radiotherapy a small translation or rotation of the tumor can lead to errors in dose delivery. Current best practice in radiotherapy accounts for tumor translations, but is unable to address rotation due to a lack of a reliable real-time estimate. We have developed a method based on the iterative closest point (ICP) algorithm that can compute rotation from kilovoltage x-ray images acquired during radiation treatment delivery. A total of 11 748 kilovoltage (kV) images acquired from ten patients (one fraction for each patient) were used to evaluate our tumor rotation algorithm. For each kV image, the three dimensional coordinates of three fiducial markers inside the prostate were calculated. The three dimensional coordinates were used as input to the ICP algorithm to calculate the real-time tumor rotation and translation around three axes. The results show that the root mean square error was improved for real-time calculation of tumor displacement from a mean of 0.97 mm with the stand alone translation to a mean of 0.16 mm by adding real-time rotation and translation displacement with the ICP algorithm. The standard deviation (SD) of rotation for the ten patients was 2.3°, 0.89° and 0.72° for rotation around the right–left (RL), anterior–posterior (AP) and superior–inferior (SI) directions respectively. The correlation between all six degrees of freedom showed that the highest correlation belonged to the AP and SI translation with a correlation of 0.67. The second highest correlation in our study was between the rotation around RL and rotation around AP, with a correlation of −0.33. Our real-time algorithm for calculation of rotation also confirms previous studies that have shown the maximum SD belongs to AP translation and rotation around RL. ICP is a reliable and fast algorithm for estimating real-time tumor rotation which could create a pathway to investigational clinical treatment studies requiring

A charge-pump 60kV modulator for the ISOLDE target extraction voltage

CERN Document Server

Barlow, R A; Fowler, A; Gaudillet, H; Gharsa, T; Schipper, J

2015-01-01

The ISOLDE facility at CERN provides radioactive ion beams to a number of experimental stations. These ions are produced by a metal target, floating at 60 kV, which is impacted by a 1.4 GeV high intensity proton beam. The ions are then accelerated by a grounded extraction electrode to 60 keV, before transport to the experimental area. During proton beam impact extremely high ionisation of the volume around the target gives rise to significant leakage current which results in loss of charge on the effective target capacitance of approximately 6 nF. If short life-time isotopes are to be studied, the 60 kV must be re-established within a maximum of 10 ms. Recharging the target capacitance to 60 kV and to the required stability of better than 10-4 precludes a direct charging system and an alternative method of re-establishing the 60 kV is used. The present system [1], in operation since 1991, employs a resonant circuit which is triggered 35 µs prior to beam impact. This circuit transfers the charge on the effec...

SU-E-I-23: A General KV Constrained Optimization of CNR for CT Abdominal Imaging

International Nuclear Information System (INIS)

Weir, V; Zhang, J

2015-01-01

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

SU-E-I-23: A General KV Constrained Optimization of CNR for CT Abdominal Imaging

Energy Technology Data Exchange (ETDEWEB)

Weir, V; Zhang, J [University of Kentucky, Lexington, KY (United States)

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.

A phosphoinositide 3-kinase (PI3K)-serum- and glucocorticoid-inducible kinase 1 (SGK1) pathway promotes Kv7.1 channel surface expression by inhibiting Nedd4-2 protein

DEFF Research Database (Denmark)

Andersen, Martin Nybo; Krzystanek, Katarzyna; Petersen, Frederic

2013-01-01

Epithelial cell polarization involves several kinase signaling cascades that eventually divide the surface membrane into an apical and a basolateral part. One kinase, which is activated during the polarization process, is phosphoinositide 3-kinase (PI3K). In MDCK cells, the basolateral potassium...... channel Kv7.1 requires PI3K activity for surface-expression during the polarization process. Here, we demonstrate that Kv7.1 surface expression requires tonic PI3K activity as PI3K inhibition triggers endocytosis of these channels in polarized MDCK. Pharmacological inhibition of SGK1 gave similar results...... as PI3K inhibition, whereas overexpression of constitutively active SGK1 overruled it, suggesting that SGK1 is the primary downstream target of PI3K in this process. Furthermore, knockdown of the ubiquitin ligase Nedd4-2 overruled PI3K inhibition, whereas a Nedd4-2 interaction-deficient Kv7.1 mutant...

Inhibitory effects of telmisartan on culture and proliferation of and Kv1.3 potassium channel expression in peripheral blood CD4+ T lymphocytes from Xinjiang Kazakh patients with hypertension

Directory of Open Access Journals (Sweden)

Sha-Sha Huang

2016-10-01

Full Text Available Introduction: Activation of T lymphocytes, for which potassium channels are essential, is involved in the development of hypertension. In this study, we explored the inhibitory effects of telmisartan on the culture and proliferation of and Kv1.3 potassium channel expression in peripheral blood CD4+ T lymphocytes derived from Xinjiang Kazakh patients with hypertension. Methods: CD4+ T-cell samples from hypertensive Kazakh patients and healthy Kazakh people were divided into healthy control, case control, telmisartan, and 4-aminopytidine groups. Changes in the expression levels of interleukin (IL-6 and IL-17 in the blood of the healthy control and case control subjects were detected by enzyme-linked immunosorbent assay. Peripheral blood CD4+ T lymphocytes were first activated and proliferated in vitro and then incubated for 0, 24, and 48 h under various treatment conditions. Thereafter, changes in CD4+ T-lymphocytic proliferation were determined using Cell Counting Kit-8 and microscope photography. Changes in messenger RNA (mRNA and protein expression of the Kv1.3 potassium channel in CD4+ T lymphocytes were detected using real-time quantitative polymerase chain reaction and Western blots, respectively. Results: The IL-6 and IL-17 expression levels were significantly higher in the blood of the hypertensive Kazakh patients than in the healthy Kazakh people. Telmisartan inhibited T-lymphocytic proliferation, as well as the mRNA and protein expression of the Kv1.3 potassium channel in CD4+ T lymphocytes, and the inhibitory effects were time-dependent, with the strongest inhibition observed after 48 h and significantly weaker inhibition observed after 24 h of treatment. Conclusions: Telmisartan may potentially regulate hypertensive inflammatory responses by inhibiting T-lymphocytic proliferation and Kv1.3 potassium channel expression in CD4+ T lymphocytes.

The anticonvulsant retigabine suppresses neuronal Kv2-mediated currents

DEFF Research Database (Denmark)

Stas, Jeroen I; Bocksteins, Elke; Jensen, Camilla S

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...

Protection system for 11kV network using arc noise

International Nuclear Information System (INIS)

Burdi, M.K.; Memon, A.S.; Shaikh, S.A.

2000-01-01

Extensive research work is being done on protecting devices for 11KV network using arc noise and fault noise frequencies in relay to operate a circuit breaker; The relay works on the principle of detecting fault and extracting voltage signal output from the noise frequencies across filter. The voltage development without amplification, is enough to operate the circuit breaker. Sensitivity of the circuit breaker. In this paper design, operation and application of the relay are described. (author)

Radiation and contrast agent doses reductions by using 80-kV tube voltage in coronary computed tomographic angiography: A comparative study

Energy Technology Data Exchange (ETDEWEB)

Cao, Jian-xin [Department of Radiology, Wuhan 161th Hospital, Wuhan (China); Wang, Yi-min, E-mail: wym6669@yahoo.com.cn [Department of Radiology, Wuhan 161th Hospital, Wuhan (China); Lu, Jin-guo [Department of Cardiology, Asia Heart Hospital, Wuhan (China); Zhang, Yu; Wang, Peng; Yang, Cheng [Department of Radiology, Wuhan 161th Hospital, Wuhan (China)

2014-02-15

Objective: To investigate the effects of 80-kilovoltage (kV) tube voltage coronary computed tomographic angiography (CCTA) with a reduced amount of contrast agent on qualitative and quantitative image quality parameters and on radiation dose in patients with a body mass index (BMI) <23.0 kg/m{sup 2}. Methods: One hundred and twenty consecutive patients with a BMI <23.0 kg/m{sup 2} and a low calcium load undergoing retrospective electrocardiogram (ECG)-gated dual-source CCTA were randomized into two groups [standard-tube voltage (120-kV) vs. low-tube voltage (80-kV)]. The injection flow rate of contrast agent (350 mg I/mL) was adjusted to body weight of each patient (4.5–5.5 mL/s in the 120-kV group and 2.8–3.8 mL/s in the 80-kV group). Radiation and contrast agent doses were evaluated. Quantitative image quality parameters and figure of merit (FOM) of coronary artery were evaluated. Each coronary segment was evaluated for image quality on a 4-point scale. Results: Compared with the 120-kV group, effective dose and amount of contrast agent in the 80-kV group were decreased by 57.8% and 30.5% (effective dose:2.7 ± 0.5vs. 6.4 ± 1.3 mSv; amount of contrast agent:57.1 ± 3.2 vs. 82.1 ± 6.1 mL; both p < 0.0001), respectively. Image noise was 22.7 ± 2.1 HU for 120-kV images and 33.2 ± 5.2 HU for 80-kV images (p < 0.0001). Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in the proximal right coronary artery (RCA) and left main coronary artery (LMA) were all lower in 80-kV than 120-kV images (SNR in the proximal RCA: 16.5 ± 1.8 vs. 19.4 ± 2.8; SNR in the LMA: 16.3 ± 2.0 vs.19.6 ± 2.7; CNR in the proximal RCA: 19.4 ± 2.3 vs.22.9 ± 3.0; CNR in the LMA: 18.8 ± 2.4 vs. 22.7 ± 2.9; all p < 0.0001). FOM were all significantly higher in 80-kV than 120-kV images (proximal RCA: 146.7 ± 45.1 vs. 93.4 ± 32.0; LMA: 139.1 ± 47.2 vs. 91.6 ± 31.1; all p < 0.0001). There was no significant difference in image quality score between the two groups (3.3 ± 0

Radiation and contrast agent doses reductions by using 80-kV tube voltage in coronary computed tomographic angiography: A comparative study

International Nuclear Information System (INIS)

Cao, Jian-xin; Wang, Yi-min; Lu, Jin-guo; Zhang, Yu; Wang, Peng; Yang, Cheng

2014-01-01

Objective: To investigate the effects of 80-kilovoltage (kV) tube voltage coronary computed tomographic angiography (CCTA) with a reduced amount of contrast agent on qualitative and quantitative image quality parameters and on radiation dose in patients with a body mass index (BMI) <23.0 kg/m 2 . Methods: One hundred and twenty consecutive patients with a BMI <23.0 kg/m 2 and a low calcium load undergoing retrospective electrocardiogram (ECG)-gated dual-source CCTA were randomized into two groups [standard-tube voltage (120-kV) vs. low-tube voltage (80-kV)]. The injection flow rate of contrast agent (350 mg I/mL) was adjusted to body weight of each patient (4.5–5.5 mL/s in the 120-kV group and 2.8–3.8 mL/s in the 80-kV group). Radiation and contrast agent doses were evaluated. Quantitative image quality parameters and figure of merit (FOM) of coronary artery were evaluated. Each coronary segment was evaluated for image quality on a 4-point scale. Results: Compared with the 120-kV group, effective dose and amount of contrast agent in the 80-kV group were decreased by 57.8% and 30.5% (effective dose:2.7 ± 0.5vs. 6.4 ± 1.3 mSv; amount of contrast agent:57.1 ± 3.2 vs. 82.1 ± 6.1 mL; both p < 0.0001), respectively. Image noise was 22.7 ± 2.1 HU for 120-kV images and 33.2 ± 5.2 HU for 80-kV images (p < 0.0001). Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in the proximal right coronary artery (RCA) and left main coronary artery (LMA) were all lower in 80-kV than 120-kV images (SNR in the proximal RCA: 16.5 ± 1.8 vs. 19.4 ± 2.8; SNR in the LMA: 16.3 ± 2.0 vs.19.6 ± 2.7; CNR in the proximal RCA: 19.4 ± 2.3 vs.22.9 ± 3.0; CNR in the LMA: 18.8 ± 2.4 vs. 22.7 ± 2.9; all p < 0.0001). FOM were all significantly higher in 80-kV than 120-kV images (proximal RCA: 146.7 ± 45.1 vs. 93.4 ± 32.0; LMA: 139.1 ± 47.2 vs. 91.6 ± 31.1; all p < 0.0001). There was no significant difference in image quality score between the two groups (3.3 ± 0.8 vs. 3

Macroscopic Quantum Resonators (MAQRO): 2015 update

International Nuclear Information System (INIS)

Kaltenbaek, Rainer; Aspelmeyer, Markus; Kiesel, Nikolai; Barker, Peter F.; Bose, Sougato; Bassi, Angelo; Bateman, James; Bongs, Kai; Cruise, Adrian Michael; Braxmaier, Claus; Brukner, Caslav; Christophe, Bruno; Rodrigues, Manuel; Chwalla, Michael; Johann, Ulrich; Cohadon, Pierre-Francois; Heidmann, Antoine; Lambrecht, Astrid; Reynaud, Serge; Curceanu, Catalina; Dholakia, Kishan; Mazilu, Michael; Diosi, Lajos; Doeringshoff, Klaus; Peters, Achim; Ertmer, Wolfgang; Rasel, Ernst M.; Gieseler, Jan; Novotny, Lukas; Rondin, Loic; Guerlebeck, Norman; Herrmann, Sven; Laemmerzahl, Claus; Hechenblaikner, Gerald; Hossenfelder, Sabine; Kim, Myungshik; Milburn, Gerard J.; Mueller, Holger; Paternostro, Mauro; Pikovski, Igor; Pilan Zanoni, Andre; Riedel, Charles Jess; Roura, Albert; Schleich, Wolfgang P.; Schmiedmayer, Joerg; Schuldt, Thilo; Schwab, Keith C.; Tajmar, Martin; Tino, Guglielmo M.; Ulbricht, Hendrik; Ursin, Rupert; Vedral, Vlatko

2016-01-01

Do the laws of quantum physics still hold for macroscopic objects - this is at the heart of Schroedinger's cat paradox - or do gravitation or yet unknown effects set a limit for massive particles? What is the fundamental relation between quantum physics and gravity? Ground-based experiments addressing these questions may soon face limitations due to limited free-fall times and the quality of vacuum and microgravity. The proposed mission Macroscopic Quantum Resonators (MAQRO) may overcome these limitations and allow addressing such fundamental questions. MAQRO harnesses recent developments in quantum optomechanics, high-mass matter-wave interferometry as well as state-of-the-art space technology to push macroscopic quantum experiments towards their ultimate performance limits and to open new horizons for applying quantum technology in space. The main scientific goal is to probe the vastly unexplored 'quantum-classical' transition for increasingly massive objects, testing the predictions of quantum theory for objects in a size and mass regime unachievable in ground-based experiments. The hardware will largely be based on available space technology. Here, we present the MAQRO proposal submitted in response to the 4th Cosmic Vision call for a medium-sized mission (M4) in 2014 of the European Space Agency (ESA) with a possible launch in 2025, and we review the progress with respect to the original MAQRO proposal for the 3rd Cosmic Vision call for a medium-sized mission (M3) in 2010. In particular, the updated proposal overcomes several critical issues of the original proposal by relying on established experimental techniques from high-mass matter-wave interferometry and by introducing novel ideas for particle loading and manipulation. Moreover, the mission design was improved to better fulfill the stringent environmental requirements for macroscopic quantum experiments. (orig.)

Macroscopic Quantum Resonators (MAQRO): 2015 update

Energy Technology Data Exchange (ETDEWEB)

Kaltenbaek, Rainer [University of Vienna, Vienna Center for Quantum Science and Technology, Vienna (Austria); Aspelmeyer, Markus; Kiesel, Nikolai [University of Vienna, Vienna Center for Quantum Science and Technology, Vienna (Austria); Barker, Peter F.; Bose, Sougato [University College London, Department of Physics and Astronomy, London (United Kingdom); Bassi, Angelo [University of Trieste, Department of Physics, Trieste (Italy); INFN - Trieste Section, Trieste (Italy); Bateman, James [University of Swansea, Department of Physics, College of Science, Swansea (United Kingdom); Bongs, Kai; Cruise, Adrian Michael [University of Birmingham, School of Physics and Astronomy, Birmingham (United Kingdom); Braxmaier, Claus [University of Bremen, Center of Applied Space Technology and Micro Gravity (ZARM), Bremen (Germany); Institute of Space Systems, German Aerospace Center (DLR), Bremen (Germany); Brukner, Caslav [University of Vienna, Vienna Center for Quantum Science and Technology, Vienna (Austria); Austrian Academy of Sciences, Institute of Quantum Optics and Quantum Information (IQOQI), Vienna (Austria); Christophe, Bruno; Rodrigues, Manuel [The French Aerospace Lab, ONERA, Chatillon (France); Chwalla, Michael; Johann, Ulrich [Airbus Defence and Space GmbH, Immenstaad (Germany); Cohadon, Pierre-Francois; Heidmann, Antoine; Lambrecht, Astrid; Reynaud, Serge [ENS-PSL Research University, Laboratoire Kastler Brossel, UPMC-Sorbonne Universites, CNRS, College de France, Paris (France); Curceanu, Catalina [Laboratori Nazionali di Frascati dell' INFN, Frascati (Italy); Dholakia, Kishan; Mazilu, Michael [University of St. Andrews, School of Physics and Astronomy, St. Andrews (United Kingdom); Diosi, Lajos [Wigner Research Center for Physics, P.O. Box 49, Budapest (Hungary); Doeringshoff, Klaus; Peters, Achim [Humboldt-Universitaet zu Berlin, Institut fuer Physik, Berlin (Germany); Ertmer, Wolfgang; Rasel, Ernst M. [Leibniz Universitaet Hannover, Institut fuer Quantenoptik, Hannover (Germany); Gieseler, Jan; Novotny, Lukas; Rondin, Loic [ETH Zuerich, Photonics Laboratory, Zuerich (Switzerland); Guerlebeck, Norman; Herrmann, Sven; Laemmerzahl, Claus [University of Bremen, Center of Applied Space Technology and Micro Gravity (ZARM), Bremen (Germany); Hechenblaikner, Gerald [Airbus Defence and Space GmbH, Immenstaad (Germany); European Southern Observatory (ESO), Garching bei Muenchen (Germany); Hossenfelder, Sabine [KTH Royal Institute of Technology and Stockholm University, Nordita, Stockholm (Sweden); Kim, Myungshik [Imperial College London, QOLS, Blackett Laboratory, London (United Kingdom); Milburn, Gerard J. [University of Queensland, ARC Centre for Engineered Quantum Systems, Brisbane (Australia); Mueller, Holger [University of California, Department of Physics, Berkeley, CA (United States); Paternostro, Mauro [Queen' s University, Centre for Theoretical Atomic, Molecular and Optical Physics, School of Mathematics and Physics, Belfast (United Kingdom); Pikovski, Igor [Harvard-Smithsonian Center for Astrophysics, ITAMP, Cambridge, MA (United States); Pilan Zanoni, Andre [Airbus Defence and Space GmbH, Immenstaad (Germany); CERN - European Organization for Nuclear Research, EN-STI-TCD, Geneva (Switzerland); Riedel, Charles Jess [Perimeter Institute for Theoretical Physics, Waterloo, ON (Canada); Roura, Albert [Universitaet Ulm, Institut fuer Quantenphysik, Ulm (Germany); Schleich, Wolfgang P. [Universitaet Ulm, Institut fuer Quantenphysik, Ulm (Germany); Texas A and M University Institute for Advanced Study (TIAS), Institute for Quantum Science and Engineering (IQSE), and Department of Physics and Astronomy, College Station, TX (United States); Schmiedmayer, Joerg [Vienna University of Technology, Vienna Center for Quantum Science and Technology, Institute of Atomic and Subatomic Physics, Vienna (Austria); Schuldt, Thilo [Institute of Space Systems, German Aerospace Center (DLR), Bremen (Germany); Schwab, Keith C. [California Institute of Technology, Applied Physics, Pasadena, CA (United States); Tajmar, Martin [Technische Universitaet Dresden, Institut fuer Luft- und Raumfahrttechnik, Dresden (Germany); Tino, Guglielmo M. [Universita di Firenze, Dipartimento di Fisica e Astronomia and LENS, INFN, Sesto Fiorentino, Firenze (Italy); Ulbricht, Hendrik [University of Southampton, Physics and Astronomy, Southampton (United Kingdom); Ursin, Rupert [Austrian Academy of Sciences, Institute of Quantum Optics and Quantum Information (IQOQI), Vienna (Austria); Vedral, Vlatko [University of Oxford, Atomic and Laser Physics, Clarendon Laboratory, Oxford (United Kingdom); National University of Singapore, Center for Quantum Technologies, Singapore (SG)

2016-12-15

Do the laws of quantum physics still hold for macroscopic objects - this is at the heart of Schroedinger's cat paradox - or do gravitation or yet unknown effects set a limit for massive particles? What is the fundamental relation between quantum physics and gravity? Ground-based experiments addressing these questions may soon face limitations due to limited free-fall times and the quality of vacuum and microgravity. The proposed mission Macroscopic Quantum Resonators (MAQRO) may overcome these limitations and allow addressing such fundamental questions. MAQRO harnesses recent developments in quantum optomechanics, high-mass matter-wave interferometry as well as state-of-the-art space technology to push macroscopic quantum experiments towards their ultimate performance limits and to open new horizons for applying quantum technology in space. The main scientific goal is to probe the vastly unexplored 'quantum-classical' transition for increasingly massive objects, testing the predictions of quantum theory for objects in a size and mass regime unachievable in ground-based experiments. The hardware will largely be based on available space technology. Here, we present the MAQRO proposal submitted in response to the 4th Cosmic Vision call for a medium-sized mission (M4) in 2014 of the European Space Agency (ESA) with a possible launch in 2025, and we review the progress with respect to the original MAQRO proposal for the 3rd Cosmic Vision call for a medium-sized mission (M3) in 2010. In particular, the updated proposal overcomes several critical issues of the original proposal by relying on established experimental techniques from high-mass matter-wave interferometry and by introducing novel ideas for particle loading and manipulation. Moreover, the mission design was improved to better fulfill the stringent environmental requirements for macroscopic quantum experiments. (orig.)

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

International Nuclear Information System (INIS)

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 μs, 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 ∼ 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 μs 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

CGM ApS Årsberetning til DANAK

DEFF Research Database (Denmark)

De Chiffre, Leonardo

Denne årsberetning omfatter CGM ApS' akkrediterede virksomhed i kalenderåret 2003. Årsberetningen er udarbejdet til DANAK (Dansk Akkreditering, ErhvervsfremmeStyrelsen), som led i opfyldelsen af laboratoriets informationspligt i henhold til gældende regler.......Denne årsberetning omfatter CGM ApS' akkrediterede virksomhed i kalenderåret 2003. Årsberetningen er udarbejdet til DANAK (Dansk Akkreditering, ErhvervsfremmeStyrelsen), som led i opfyldelsen af laboratoriets informationspligt i henhold til gældende regler....

Renal involvement in the antiphospholipid syndrome (APS)-APS nephropathy.

Science.gov (United States)

Tektonidou, Maria G

2009-06-01

Although the kidney represents a major target organ in antiphospholipid syndrome (APS), renal involvement in APS was poorly recognized until recently. The most well-recognized renal manifestations of APS are the renal artery thrombosis/stenosis, renal infarction, hypertension, renal vein thrombosis, end-stage renal disease, increased allograft vascular thrombosis, some types of glomerular disease, and a small-vessel vaso-occlusive nephropathy, recently defined as APS nephropathy. APS nephropathy was first described in primary APS patients, characterized by acute thrombotic lesions in glomeruli and/or arterioles (thrombotic microangiopathy) and chronic vascular lesions such as fibrous intimal hyperplasia of arterioles and interlobular arteries, organized thrombi with or without recanalization, and fibrous arterial and arteriolar occlusions or focal cortical atrophy. APS nephropathy was also detected in further studies including patients with systemic lupus erythematosus (SLE)-related APS and SLE/non-APS patients with positive antiphospholipid antibodies, independently of lupus nephritis. The same histologic lesions, especially thrombotic mictroangiopathy, were also observed in patients with catastrophic APS. The most frequent clinical and laboratory characteristics of APS nephropathy in all the above groups of patients are hypertension (often severe), proteinuria (ranging from mild to nephrotic range), hematuria, and acute or chronic renal insufficiency.

2.3-MW Medium-Voltage, Three-Level Wind Energy Inverter Applying a Unique Bus Structure and 4.5-kV Si/SiC Hybrid Isolated Power Modules: Preprint

Energy Technology Data Exchange (ETDEWEB)

Erdman, W.; Keller, J.; Grider, D.; VanBrunt, E.

2014-11-01

A high-efficiency, 2.3-MW, medium-voltage, three-level inverter utilizing 4.5-kV Si/SiC (silicon carbide) hybrid modules for wind energy applications is discussed. The inverter addresses recent trends in siting the inverter within the base of multimegawatt turbine towers. A simplified split, three-layer laminated bus structure that maintains low parasitic inductances is introduced along with a low-voltage, high-current test method for determining these inductances. Feed-thru bushings, edge fill methods, and other design features of the laminated bus structure provide voltage isolation that is consistent with the 10.4-kV module isolation levels. Inverter efficiency improvement is a result of the (essential) elimination of the reverse recovery charge present in 4.5-kV Si PIN diodes, which can produce a significant reduction in diode turn-off losses as well as insulated-gate bipolar transistor (IGBT) turn-on losses. The hybrid modules are supplied in industry-standard 140 mm x 130 mm and 190 mm x 130 mm packages to demonstrate direct module substitution into existing inverter designs. A focus on laminated bus/capacitor-bank/module subassembly level switching performance is presented.

A new and specific non-NMDA receptor antagonist, FG 9065, blocks L-AP4-evoked depolarization in rat cerebral cortex.

Science.gov (United States)

Sheardown, M J

1988-04-13

L(+)-AP4 (2-amino-4-phosphonobutyrate) depolarized slices of rat cerebral cortex, when applied following a 2 min priming application of quisqualate. This response diminishes with time and is not seen after NMDA application. A new selective non-N-methyl-D-aspartate (NMDA) antagonist, 6-cyano-7-nitro-2,3-dihydroxyquinoxaline (FG 9065), inhibits the L(+)-AP4 depolarization. It is argued that the response is mediated indirectly by postsynaptic quisqualate receptors.

Fission observables from 4D Langevin calculations with macroscopic transport coefficients

Directory of Open Access Journals (Sweden)

Usang Mark D.

2018-01-01

Full Text Available We have extended the Langevin equations to 4 dimensions (4D by allowing the independent deformation for the left (δ1 and right fragments (δ2 of the fissioning nucleus. At the moment we are only able to use them in conjunction with the macroscopic transport coefficients. Nevertheless, we can see a considerable improvement in the preliminary results for the fission observables, especially those related to the total kinetic energy (TKE of fission fragments. By plotting the TKE distributions we have revealed the super-long fission modes in 236U and super-short fission modes in 257Fm. By plotting the distribution of δ against the fragment’s TKE we have noted a correlation between the values of δ and Brosa’s fission modes. We have found that the standard fission modes correspond to prolate tips of the light fragments while the complementary heavy fragments have oblate fission tips. On the other hand, if both fragments were prolate at the tips, we get super-long fission modes. If both fragments were oblate at the tips, we get super-short fission modes.

Major Refit for CERN's 400 kV Substation

CERN Multimedia

2001-01-01

The 400 kV substation on the Prévessin site brings in the electricity that powers CERN's accelerators and the majority of the Laboratory's installations. It was originally built in the 1970s for the SPS, and is one of only five privately owned 400 kV sub-stations in France. Three of the others belong to the national railway company, SNCF, supplying the Paris-Marseilles TGV line, the other is at the Cadarache research centre near mouth of the Rhone. After nearly thirty years of service, CERN's substation has just undergone a complete overhaul. The new main 18 kV switchboard for the SPS pulsed network. The electricity supply for the original Prévessin substation was from the 400 kV EDF network, delivered through three 90 MW transformers at 18 kV to the SPS pulsed network, With the arrival of LEP, two 110 MW transformers were added to supply the new accelerator. Now, as CERN gears up for the LHC, additional pulsed power capacity is needed to supply the transfer lines carrying protons from...

Rapid internalization of the oncogenic K+ channel K(V10.1.

Directory of Open Access Journals (Sweden)

Tobias Kohl

Full Text Available K(V10.1 is a mammalian brain voltage-gated potassium channel whose ectopic expression outside of the brain has been proven relevant for tumor biology. Promotion of cancer cell proliferation by K(V10.1 depends largely on ion flow, but some oncogenic properties remain in the absence of ion permeation. Additionally, K(V10.1 surface populations are small compared to large intracellular pools. Control of protein turnover within cells is key to both cellular plasticity and homeostasis, and therefore we set out to analyze how endocytic trafficking participates in controlling K(V10.1 intracellular distribution and life cycle. To follow plasma membrane K(V10.1 selectively, we generated a modified channel of displaying an extracellular affinity tag for surface labeling by α-bungarotoxin. This modification only minimally affected K(V10.1 electrophysiological properties. Using a combination of microscopy and biochemistry techniques, we show that K(V10.1 is constitutively internalized involving at least two distinct pathways of endocytosis and mainly sorted to lysosomes. This occurs at a relatively fast rate. Simultaneously, recycling seems to contribute to maintain basal K(V10.1 surface levels. Brief K(V10.1 surface half-life and rapid lysosomal targeting is a relevant factor to be taken into account for potential drug delivery and targeting strategies directed against K(V10.1 on tumor cells.

Macroscopic quantum waves in non local theories

International Nuclear Information System (INIS)

Ventura, I.

1979-01-01

By means of an expansion in the density, it is shown that Macroscopic Quantum Waves also appear in non local theories. This result reinforces the conjecture that these waves should exist in liquid 4 He [pt

An operational 150 kV microfocus rod anode X-ray system for nondestructive testing

International Nuclear Information System (INIS)

Fontijn, E.A.

1978-01-01

This paper describes an operational state of the art 150 kV microfocus rod anode X-ray system having ultra-high radiographic resolution capabilities. A cocal spot size of 0.050 mm is provided. Heretofore unattainable long rod anode lengths coupled with very small diameters are now possible using mini-magnetic lens technology. Over-all rod anode diameters as small as 9 mm with useful lengths of 1 m or more are possible, permitting panoramic inspections where previously only lower resolution radioisotope radiographic techniques were possible. Radiographic sensitivity of better than 1% has been reported with film-focal-distances on the order of 8 mm through 3 mm of steel. The system has been successfully applied to steam generator and heat exchanger tube-to-tubesheet weldments in both Europe and the USA. Other application areas include marine and aircraft jet engine inspection and numerous other applications where high reliability requirements indicate the use of a ultra-sensitive radiographic technique as is routinely demonstrated with the 150 kV Microfocus Rod Anode X-ray System. (orig.) [de

Rank distributions: A panoramic macroscopic outlook

Science.gov (United States)

Eliazar, Iddo I.; Cohen, Morrel H.

2014-01-01

This paper presents a panoramic macroscopic outlook of rank distributions. We establish a general framework for the analysis of rank distributions, which classifies them into five macroscopic "socioeconomic" states: monarchy, oligarchy-feudalism, criticality, socialism-capitalism, and communism. Oligarchy-feudalism is shown to be characterized by discrete macroscopic rank distributions, and socialism-capitalism is shown to be characterized by continuous macroscopic size distributions. Criticality is a transition state between oligarchy-feudalism and socialism-capitalism, which can manifest allometric scaling with multifractal spectra. Monarchy and communism are extreme forms of oligarchy-feudalism and socialism-capitalism, respectively, in which the intrinsic randomness vanishes. The general framework is applied to three different models of rank distributions—top-down, bottom-up, and global—and unveils each model's macroscopic universality and versatility. The global model yields a macroscopic classification of the generalized Zipf law, an omnipresent form of rank distributions observed across the sciences. An amalgamation of the three models establishes a universal rank-distribution explanation for the macroscopic emergence of a prevalent class of continuous size distributions, ones governed by unimodal densities with both Pareto and inverse-Pareto power-law tails.

Kv10.1 potassium channel: from the brain to the tumors.

Science.gov (United States)

Cázares-Ordoñez, V; Pardo, L A

2017-10-01

The KCNH1 gene encodes the Kv10.1 (Eag1) ion channel, a member of the EAG (ether-à-go-go) family of voltage-gated potassium channels. Recent studies have demonstrated that KCHN1 mutations are implicated in Temple-Baraitser and Zimmermann-Laband syndromes and other forms of developmental deficits that all present with mental retardation and epilepsy, suggesting that Kv10.1 might be important for cognitive development in humans. Although the Kv10.1 channel is mainly expressed in the mammalian brain, its ectopic expression occurs in 70% of human cancers. Cancer cells and tumors expressing Kv10.1 acquire selective advantages that favor cancer progression through molecular mechanisms that involve several cellular pathways, indicating that protein-protein interactions may be important for Kv10.1 influence in cell proliferation and tumorigenesis. Several studies on transcriptional and post-transcriptional regulation of Kv10.1 expression have shown interesting mechanistic insights about Kv10.1 role in oncogenesis, increasing the importance of identifying the cellular factors that regulate Kv10.1 expression in tumors.

Macroscopic quantum waves in non local theories

International Nuclear Information System (INIS)

Ventura, I.

1979-01-01

By means of an expansion in the density, it is shown that Macroscopic Quantum Waves also apear in non local theories. This result reinforces the conjecture that these waves should exist in liquid 4 He. (Author) [pt

In vitro measurement of CT density and estimation of stenosis related to coronary soft plaque at 100 kV and 120 kV on ECG-triggered scan

Energy Technology Data Exchange (ETDEWEB)

Horiguchi, Jun, E-mail: horiguch@hiroshima-u.ac.jp [Department of Clinical Radiology, Hiroshima University Hospital, 1-2-3, Kasumi-cho, Minami-ku, Hiroshima 734-8551 (Japan); Fujioka, Chikako, E-mail: fujioka@hiroshima-u.ac.jp [Department of Clinical Radiology, Hiroshima University Hospital, 1-2-3, Kasumi-cho, Minami-ku, Hiroshima 734-8551 (Japan); Kiguchi, Masao, E-mail: kiguchi@hiroshima-u.ac.jp [Department of Clinical Radiology, Hiroshima University Hospital, 1-2-3, Kasumi-cho, Minami-ku, Hiroshima 734-8551 (Japan); Yamamoto, Hideya, E-mail: hideyayama@hiroshima-u.ac.jp [Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical Sciences and Hiroshima University Hospital, 1-2-3, Kasumi-cho, Minami-ku, Hiroshima 734-8551 (Japan); Shen, Yun, E-mail: Yuna.Shen@ge.com [CT Lab of Great China, GE Healthcare, L12 and L15, Office Tower, Langham Place, 8 Argyle Street, Mongkok Kowloon (Hong Kong); Kihara, Yasuki, E-mail: ykihara@hiroshima-u.ac.jp [Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical Sciences and Hiroshima University Hospital, 1-2-3, Kasumi-cho, Minami-ku, Hiroshima 734-8551 (Japan)

2011-02-15

Purpose: The purpose of the study was to compare 100 kV and 120 kV prospective electrocardiograph (ECG)-triggered axial coronary 64-detector CT angiography (64-MDCTA) in soft plaque diagnosis. Materials and methods: Coronary artery models (n = 5) with artificial soft plaques (-32 HU to 53 HU at 120 kV) with three stenosis levels (25%, 50% and 75%) on a cardiac phantom (mimicking slim patient's environment) were scanned in heart rates of 55, 60 and 65 beats per minute (bpm). Four kinds of intracoronary enhancement (205 HU, 241 HU, 280 HU and 314 HU) were simulated. The soft plaque density and the measurement error of stenosis (in percentage), evaluated by two independent observers, were compared between 100 kV and 120 kV. The radiation dose was estimated. Results: Interobserver correlation of the measurement was excellent (density; r = 0.95 and stenosis measure; r = 0.97). Neither the density of soft plaque nor the measurement error of stenosis was different between 100 kV and 120 kV (p = 0.22 and 0.08). The estimated radiation doses were 2.0 mSv and 3.3 mSv (in 14 cm coverage) on 100 kV and 120 kV prospective ECG-triggered axial scans, respectively. Conclusion: The 100 kV prospective ECG-triggered coronary MDCTA has comparable performance to 120 kV coronary CTA in terms of soft plaque densitometry and measurement of stenosis, with a reduced effective dose of 2 mSv.

AP1000 design and construction integration

International Nuclear Information System (INIS)

Winters, James W.; Clelland, Jill A.

2004-01-01

Construction costs of commercial nuclear generating plants must be reduced in order to expand the future use of nuclear energy. Two of the drivers of plant construction costs are the cost of financing during the construction duration and the substantial amount of skilled craft labor hours needed on site during construction. The application of information technology (IT) has been used to understand and reduce both of these drivers by establishing parallel construction paths using modules and integrating construction sequence review into the design process. In a program sponsored by EPRI, Westinghouse has modeled the construction of AP1000 in '4D' to show its viability, to improve its logic, to improve the plant design for constructibility and overall to reduce time and risk in the construction schedule. The design of most of AP1000 was constrained to be a duplicate of AP600 except where components required expansion for the higher power level. As a result, the construction schedule for AP1000 is as mature and as robust as that for AP600. Two areas important to the construction of AP1000 did require some design work because they could not remain the same as AP1000. First, the turbine building had to be redesigned to accommodate the larger turbine and its support systems. Again, as much of the AP600 design and philosophy as possible was retained. The building required enlargement and the basemat, foundations, steel structure and structural modules required modification. As concrete, steel, and equipment were defined by the designers, they were matched to the original AP600 turbine building schedule. This forced designers to assemble files to be consistent with building assembly activities and to think about constructibility as they defined the final design. Second, the reinforcement structure within the concrete under and supporting the containment vessel required detail design. Westinghouse was fortunate to have the constructor Obayashi of Japan recommend a detailed

Rearrangement of potassium ions and Kv1.1/Kv1.2 potassium channels in regenerating axons following end-to-end neurorrhaphy: ionic images from TOF-SIMS.

Science.gov (United States)

Liu, Chiung-Hui; Chang, Hung-Ming; Wu, Tsung-Huan; Chen, Li-You; Yang, Yin-Shuo; Tseng, To-Jung; Liao, Wen-Chieh

2017-10-01

The voltage-gated potassium channels Kv1.1 and Kv1.2 that cluster at juxtaparanodal (JXP) regions are essential in the regulation of nerve excitability and play a critical role in axonal conduction. When demyelination occurs, Kv1.1/Kv1.2 activity increases, suppressing the membrane potential nearly to the equilibrium potential of K + , which results in an axonal conduction blockade. The recovery of K + -dependent communication signals and proper clustering of Kv1.1/Kv1.2 channels at JXP regions may directly reflect nerve regeneration following peripheral nerve injury. However, little is known about potassium channel expression and its relationship with the dynamic potassium ion distribution at the node of Ranvier during the regenerative process of peripheral nerve injury (PNI). In the present study, end-to-end neurorrhaphy (EEN) was performed using an in vivo model of PNI. The distribution of K + at regenerating axons following EEN was detected by time-of-flight secondary-ion mass spectrometry. The specific localization and expression of Kv1.1/Kv1.2 channels were examined by confocal microscopy and western blotting. Our data showed that the re-establishment of K + distribution and intensity was correlated with the functional recovery of compound muscle action potential morphology in EEN rats. Furthermore, the re-clustering of Kv1.1/1.2 channels 1 and 3 months after EEN at the nodal region of the regenerating nerve corresponded to changes in the K + distribution. This study provided direct evidence of K + distribution in regenerating axons for the first time. We proposed that the Kv1.1/Kv1.2 channels re-clustered at the JXP regions of regenerating axons are essential for modulating the proper patterns of K + distribution in axons for maintaining membrane potential stability after EEN.

A Common Structural Component for β-Subunit Mediated Modulation of Slow Inactivation in Different KV Channels

DEFF Research Database (Denmark)

Strutz-Seebohm, Nathalie; Henrion, Ulrike; Schmitt, Nicole

2013-01-01

Background/Aims: Potassium channels are tetrameric proteins providing potassium selective passage through lipid embedded proteinaceous pores with highest fidelity. The selectivity results from binding to discrete potassium binding sites and stabilization of a hydrated potassium ion in a central...... internal cavity. The four potassium binding sites, generated by the conserved TTxGYGD signature sequence are formed by the backbone carbonyls of the amino acids TXGYG. Residues KV1.5-Val481, KV4.3-Leu368 and KV7.1- Ile 313 represent the amino acids in the X position of the respective channels. Methods...

Dual Regulation of Voltage-Sensitive Ion Channels by PIP2

Directory of Open Access Journals (Sweden)

Aldo A Rodríguez Menchaca

2012-09-01

Full Text Available Over the past 16 years, there has been an impressive number of ion channels shown to be sensitive to the major phosphoinositide in the plasma membrane, phosphatidilinositol 4,5-bisphosphate (PIP2. Among them are voltage-gated channels, which are crucial for both neuronal and cardiac excitability. Voltage-gated calcium (Cav channels were shown to be regulated bidirectionally by PIP2. On one hand, PIP2 stabilized their activity by reducing current rundown but on the other hand it produced a voltage-dependent inhibition by shifting the activation curve to more positive voltages. For voltage-gated potassium (Kv channels PIP2 was first shown to prevent N-type inactivation. Careful examination of the effects of PIP2 on the activation mechanism of Kv1.2 has shown a similar bidirectional regulation as in the Cav channels. The two effects could be distinguished kinetically, in terms of their sensitivities to PIP2 and by distinct molecular determinants. The rightward shift of the Kv1.2 voltage dependence implicated basic residues in the S4-S5 linker and was consistent with stabilization of the inactive state of the voltage sensor. A third type of a voltage-gated ion channel modulated by PIP2 is the hyperpolarization-activated cyclic nucleotide-gated (HCN channel. PIP2 has been shown to enhance the opening of HCN channels by shifting their voltage-dependent activation toward depolarized potentials. The sea urchin HCN channel, SpIH, showed again a PIP2-mediated bidirectional effect but in reverse order than the depolarization-activated Cav and Kv channels: a voltage-dependent potentiation, like the mammalian HCN channels, but also an inhibition of the cGMP-induced current activation. Just like the Kv1.2 channels, distinct molecular determinants underlied the PIP2 dual effects on SpIH channels. The dual regulation of these very different ion channels, all of which are voltage dependent, points to conserved mechanisms of regulation of these channels by PIP2.

Quantum equilibria for macroscopic systems

International Nuclear Information System (INIS)

Grib, A; Khrennikov, A; Parfionov, G; Starkov, K

2006-01-01

Nash equilibria are found for some quantum games with particles with spin-1/2 for which two spin projections on different directions in space are measured. Examples of macroscopic games with the same equilibria are given. Mixed strategies for participants of these games are calculated using probability amplitudes according to the rules of quantum mechanics in spite of the macroscopic nature of the game and absence of Planck's constant. A possible role of quantum logical lattices for the existence of macroscopic quantum equilibria is discussed. Some examples for spin-1 cases are also considered

Chronic electroconvulsive stimulation but not chronic restraint stress modulates mRNA expression of voltage-dependent potassium channels Kv7.2 and Kv11.1 in the rat piriform cortex

DEFF Research Database (Denmark)

Hjæresen, Marie-Louise; Hageman, Ida; Wörtwein, Gitta

2008-01-01

The mechanisms by which stress and electroconvulsive therapy exert opposite effects on the course of major depression are not known. Potential candidates might include the voltage-dependent potassium channels. Potassium channels play an important role in maintaining the resting membrane potential...... and controlling neuronal excitability. To explore this hypothesis, we examined the effects of one or several electroconvulsive stimulations and chronic restraint stress (6 h/day for 21 days) on the expression of voltage-dependent potassium channel Kv7.2, Kv11.1, and Kv11.3 mRNA in the rat brain using in situ...... hybridization. Repeated, but not acute, electroconvulsive stimulation increased Kv7.2 and Kv11.1 mRNA levels in the piriform cortex. In contrast, restraint stress had no significant effect on mRNA expression of Kv7.2, Kv11.1, or Kv11.3 in any of the brain regions examined. Thus, it appears that the investigated...

Microscopic and macroscopic bell inequalities

International Nuclear Information System (INIS)

Santos, E.

1984-01-01

The Bell inequalities, being derived for micro-systems, cannot be tested by (macroscopic) experiments without additional assumptions. A macroscopic definition of local realism is proposed which might be the starting point for deriving Bell inequalities testable without auxiliary assumptions. (orig.)

Preparation, Characterization and Thermal Degradation of Polyimide (4-APS/BTDA/SiO2 Composite Films

Directory of Open Access Journals (Sweden)

Arash Dehzangi

2012-04-01

Full Text Available Polyimide/SiO2 composite films were prepared from tetraethoxysilane (TEOS and poly(amic acid (PAA based on aromatic diamine (4-aminophenyl sulfone (4-APS and aromatic dianhydride (3,3,4,4-benzophenonetetracarboxylic dianhydride (BTDA via a sol-gel process in N-methyl-2-pyrrolidinone (NMP. The prepared polyimide/SiO2 composite films were characterized using X-ray diffraction (XRD, Fourier transform infrared spectroscopy (FTIR, scanning electron microscope (SEM and thermogravimetric analysis (TGA. The FTIR results confirmed the synthesis of polyimide (4-APS/BTDA and the formation of SiO2 particles in the polyimide matrix. Meanwhile, the SEM images showed that the SiO2 particles were well dispersed in the polyimide matrix. Thermal stability and kinetic parameters of the degradation processes for the prepared polyimide/SiO2 composite films were investigated using TGA in N2 atmosphere. The activation energy of the solid-state process was calculated using Flynn–Wall–Ozawa’s method without the knowledge of the reaction mechanism. The results indicated that thermal stability and the values of the calculated activation energies increased with the increase of the TEOS loading and the activation energy also varied with the percentage of weight loss for all compositions.

Quantum equilibria for macroscopic systems

Energy Technology Data Exchange (ETDEWEB)

Grib, A [Department of Theoretical Physics and Astronomy, Russian State Pedagogical University, St. Petersburg (Russian Federation); Khrennikov, A [Centre for Mathematical Modelling in Physics and Cognitive Sciences Vaexjoe University (Sweden); Parfionov, G [Department of Mathematics, St. Petersburg State University of Economics and Finances (Russian Federation); Starkov, K [Department of Mathematics, St. Petersburg State University of Economics and Finances (Russian Federation)

2006-06-30

Nash equilibria are found for some quantum games with particles with spin-1/2 for which two spin projections on different directions in space are measured. Examples of macroscopic games with the same equilibria are given. Mixed strategies for participants of these games are calculated using probability amplitudes according to the rules of quantum mechanics in spite of the macroscopic nature of the game and absence of Planck's constant. A possible role of quantum logical lattices for the existence of macroscopic quantum equilibria is discussed. Some examples for spin-1 cases are also considered.

Short-Circuit Degradation of 10-kV 10-A SiC MOSFET

DEFF Research Database (Denmark)

Eni, Emanuel-Petre; Beczkowski, Szymon; Munk-Nielsen, Stig

2017-01-01

The short-circuit behavior of power devices is highly relevant for converter design and fault protection. In this work, the degradation during short-circuit of a 10 kV 10 A 4H-SiC MOSFET is investigated at 6 kV DC-link voltage. The study aims to present the behavior of the device during short-circuit...... transients as it sustains increasing short-circuit pulses during its life-time. As the short-circuit pulse length increases, degradation of the device can be observed in periodically performed characterizations. The initial degradation seems to be associated with the channel region, and continuous stressing...

Up-regulation of interleukin-4 production via NF-AT/AP-1 activation in T cells by biochanin A, a phytoestrogen and its metabolites

International Nuclear Information System (INIS)

Park, Jin; Chung, Su Wol; Kim, Seung Hyun; Kim, Tae Sung

2006-01-01

Phytoestrogens are naturally occurring compounds derived from plants. Although phytoestrogens exhibit many biological functions including estrogen agonist/antagonist properties, the effect on allergic responses remains unclear. In this study, we investigated whether biochanin A, a phytoestrogen and its metabolites, genistein, p-ethylphenol and phenolic acid, affect production of IL-4, a pro-inflammatory cytokine closely associated with allergic immune responses, in primary CD4 + T cells and EL4 T lymphoma cells. Biochanin A, genistein and p-ethylphenol significantly enhanced IL-4 production from both CD4 + T cells and EL4 cells in a dose-dependent manner, while phenolic acid did not. Biochanin A, genistein and p-ethylphenol also enhanced IL-4 gene promoter activity in EL4 cells transiently transfected with IL-4 promoter constructs, but this effect was impaired in EL4 cells transfected with an IL-4 promoter construct deleted of a P4 site carrying NF-AT and AP-1 binding sites. In addition, biochanin A, genistein and p-ethylphenol increased both NF-AT and AP-1 DNA binding activities, indicating that they might enhance IL-4 production via NF-AT/AP-1 activation. Furthermore, biochanin A, genistein and p-ethylphenol increased p38 MAPK phosphorylation and PKC activity, while they did not affect ERK phosphorylation. The enhanced NF-AT DNA binding activities were suppressed by inhibitors for PI3-K and PKC, but not by p38 MAPK inhibitors. In contrast, the enhanced AP-1 DNA binding activities and p38 MAPK phosphorylation were significantly suppressed by specific inhibitors for PKC and p38 MAPK, but not by PI3-K inhibitors. These results demonstrate, for the first time, that biochanin A, genistein and p-ethylphenol enhance IL-4 production in activated T cells by two independent pathways, PI3-K/PKC/NF-AT and PKC/p38 MAPK/AP-1

A novel AP4M1 mutation in autosomal recessive cerebral palsy syndrome and clinical expansion of AP-4 deficiency

OpenAIRE

Jameel, Muhammad; Klar, Joakim; Tariq, Muhammad; Moawia, Abubakar; Altaf Malik, Naveed; Seema Waseem, Syeda; Abdullah, Uzma; Naeem Khan, Tahir; Raininko, Raili; Baig, Shahid Mahmood; Dahl, Niklas

2014-01-01

BACKGROUND: Cerebral palsy (CP) is a heterogeneous neurodevelopmental disorder associated with intellectual disability in one-third of cases. Recent findings support Mendelian inheritance in subgroups of patients with the disease. The purpose of this study was to identify a novel genetic cause of paraplegic CP with intellectual disability in a consanguineous Pakistani family. METHODS: We performed whole-exome sequencing (WES) in two brothers with CP and intellectual disability. Analysis of AP...

Improvement of the 400 kV linac electron source of AmPS

International Nuclear Information System (INIS)

Kroes, F.B.; Beuzekom, M.G. van; Dobbe, N.J.; Es, J.T. van; Jansweijer, P.P.M.; Kruijer, A.H.; Luigjes, G.; Sluijk, T.G.B.

1992-01-01

An existing linac (MEA) injects electrons into the Amsterdam Pulse Stretcher (AmPS) ring. The linac's peak current increases from 20 to 80 mA. This requires the modification of the 400 kV low emittance gun. The fourfold increase of the peak current is obtained by doubling both the gun perveance (new gun part) and the pulsed extractor voltage. To obtain optimum beam quality over this increased current range, the hot deck electronics has been exchanged by a fast high voltage FET switching supply. A built-in microprocessor, coupled to the local computer by optical fibers, is used to monitor and control the gun parameters. The 5 kV gun extractor voltage pulse shape can be monitored by means of an analog fibre transducer with build in calibration. Finally, in order to improve the energy stability of the accelerated electrons, a serial electron-tube stabilizer was added to the 400 kV DC power supply. (K.A.) 4 refs.; 6 figs

Image quality at low tube voltage (70 kV) and sinogram-affirmed iterative reconstruction for computed tomography in infants with congenital heart disease

International Nuclear Information System (INIS)

Nakagawa, Motoo; Ozawa, Yoshiyuki; Sakurai, Keita; Shimohira, Masashi; Shibamoto, Yuta; Ohashi, Kazuya; Asano, Miki; Yamaguchi, Sachiko

2015-01-01

Lower tube voltage has advantages for CT angiography, such as improved contrast To evaluate the image quality of low-voltage (70 kV) CT for congenital heart disease and the ability of sinogram-affirmed iterative reconstruction to improve image quality. Forty-six children with congenital heart disease (median age: 109 days) were examined using dual-source CT. Scans were performed at 80 kV and 70 kV in 21 and 25 children, respectively. A nonionic iodinated contrast medium (300 mg I/ml) was used for the 80-kV protocol. The contrast medium was diluted to 75% (225 mgI/mL) with saline for the 70-kV protocol. Image noise was measured in the two protocols for each group by extracting the standard deviations of a region of interest placed on the descending aorta. We then determined whether sinogram-affirmed iterative reconstruction reduced the image noise at 70 kV. There was more noise at 70 kV than at 80 kV (29 ± 12 vs 20 ± 4.8; P < 0.01). Sinogram-affirmed iterative reconstruction with grade 4 strength settings improved the noise (20 ± 5.9; P < 0.01) for the 70-kV group. Sinogram-affirmed iterative reconstruction improved the image quality of CT in congenital heart disease. (orig.)

Image quality at low tube voltage (70 kV) and sinogram-affirmed iterative reconstruction for computed tomography in infants with congenital heart disease

Energy Technology Data Exchange (ETDEWEB)

Nakagawa, Motoo; Ozawa, Yoshiyuki; Sakurai, Keita; Shimohira, Masashi; Shibamoto, Yuta [Nagoya City University Graduate School of Medical Sciences, Department of Radiology, Nagoya (Japan); Ohashi, Kazuya [Nagoya City University Hospital, Division of Central Radiology, Nagoya (Japan); Asano, Miki [Nagoya City University Graduate School of Medical Sciences, Department of Cardiovascular Surgery, Nagoya (Japan); Yamaguchi, Sachiko [Nagoya City University Graduate School of Medical Sciences, Department of Pediatrics and Neonatology, Nagoya (Japan)

2015-09-15

Lower tube voltage has advantages for CT angiography, such as improved contrast To evaluate the image quality of low-voltage (70 kV) CT for congenital heart disease and the ability of sinogram-affirmed iterative reconstruction to improve image quality. Forty-six children with congenital heart disease (median age: 109 days) were examined using dual-source CT. Scans were performed at 80 kV and 70 kV in 21 and 25 children, respectively. A nonionic iodinated contrast medium (300 mg I/ml) was used for the 80-kV protocol. The contrast medium was diluted to 75% (225 mgI/mL) with saline for the 70-kV protocol. Image noise was measured in the two protocols for each group by extracting the standard deviations of a region of interest placed on the descending aorta. We then determined whether sinogram-affirmed iterative reconstruction reduced the image noise at 70 kV. There was more noise at 70 kV than at 80 kV (29 ± 12 vs 20 ± 4.8; P < 0.01). Sinogram-affirmed iterative reconstruction with grade 4 strength settings improved the noise (20 ± 5.9; P < 0.01) for the 70-kV group. Sinogram-affirmed iterative reconstruction improved the image quality of CT in congenital heart disease. (orig.)

HVDC transmission preferred to 750 kV ac

Energy Technology Data Exchange (ETDEWEB)

1965-06-25

It is unlikely that there will be a need in Britain for ac transmission voltages above 400 kV. But with the growing load density in the large conurbations with no possibility of local generation, high voltage dc transmission is likely to be most useful. It was concluded that by 1971 the 400 kV supergrid would be nation-wide and 6,200 circuit miles should be in service. With the expansion to accommodate the large new generating stations, the 400 kV supergrid would become an extremely high power distribution network rather than a transmission system. A higher voltage for transmission is outside the rational limit of speculation for a country the size of Britain.

Preliminary analyses of AP600 using RELAP5

International Nuclear Information System (INIS)

Modro, S.M.; Beelman, R.J.; Fisher, J.E.

1991-01-01

This paper presents results of preliminary analyses of the proposed Westinghouse Electric Corporation AP600 design. AP600 is a two loop, 600 MW (e) pressurized water reactor (PWR) arranged in a two hot leg, four cold leg nuclear steam supply system (NSSS) configuration. In contrast to the present generation of PWRs it is equipped with passive emergency core coolant (ECC) systems. Also, the containment and the safety systems of the AP600 interact with the reactor coolant system and each other in a more integral fashion than present day PWRs. The containment in this design is the ultimate heat sink for removal of decay heat to the environment. Idaho National Engineering Laboratory (INEL) has studied applicability of the RELAP5 code to AP600 safety analysis and has developed a model of the AP600 for the Nuclear Regulatory Commission. The model incorporates integral modeling of the containment, NSSS and passive safety systems. Best available preliminary design data were used. Nodalization sensitivity studies were conducted to gain experience in modeling of systems and conditions which are beyond the applicability of previously established RELAP5 modeling guidelines or experience. Exploratory analyses were then undertaken to investigate AP600 system response during postulated accident conditions. Four small break LOCA calculations and two large break LOCA calculations were conducted

The Voltage-Sensing Domain of Kv7.2 Channels as a Molecular Target for Epilepsy-Causing Mutations and Anticonvulsants

Science.gov (United States)

Miceli, Francesco; Soldovieri, Maria Virginia; Iannotti, Fabio Arturo; Barrese, Vincenzo; Ambrosino, Paolo; Martire, Maria; Cilio, Maria Roberta; Taglialatela, Maurizio

2010-01-01

Understanding the molecular mechanisms underlying voltage-dependent gating in voltage-gated ion channels (VGICs) has been a major effort over the last decades. In recent years, changes in the gating process have emerged as common denominators for several genetically determined channelopathies affecting heart rhythm (arrhythmias), neuronal excitability (epilepsy, pain), or skeletal muscle contraction (periodic paralysis). Moreover, gating changes appear as the main molecular mechanism by which several natural toxins from a variety of species affect ion channel function. In this work, we describe the pathophysiological and pharmacological relevance of the gating process in voltage-gated K+ channels encoded by the Kv7 gene family. After reviewing the current knowledge on the molecular mechanisms and on the structural models of voltage-dependent gating in VGICs, we describe the physiological relevance of these channels, with particular emphasis on those formed by Kv7.2–Kv7.5 subunits having a well-established role in controlling neuronal excitability in humans. In fact, genetically determined alterations in Kv7.2 and Kv7.3 genes are responsible for benign familial neonatal convulsions, a rare seizure disorder affecting newborns, and the pharmacological activation of Kv7.2/3 channels can exert antiepileptic activity in humans. Both mutation-triggered channel dysfunction and drug-induced channel activation can occur by impeding or facilitating, respectively, channel sensitivity to membrane voltage and can affect overlapping molecular sites within the voltage-sensing domain of these channels. Thus, understanding the molecular steps involved in voltage-sensing in Kv7 channels will allow to better define the pathogenesis of rare human epilepsy, and to design innovative pharmacological strategies for the treatment of epilepsies and, possibly, other human diseases characterized by neuronal hyperexcitability. PMID:21687499

Overvoltages transferred from a network of 220 kV to 15.65 kV level of the step-up transformer in HPP 'Bajina Bašta'

Directory of Open Access Journals (Sweden)

Vukelja Petar

2011-01-01

Full Text Available The paper presents the results of research in lightning surge waves and switching overvoltages transferred from a network of 220 kV to the 15.65 kV level of the step-up transformer in HPP 'Bajina Bašta'. Analysis of survey results lead to conclusion that transferred overvoltages can endanger 15.65 kV transformer windings and stator winding insulation. It was therefore suggested for the protection of the 15.65 kV isolation to install metal oxide surge arresters at a suitable place between the power generator bus bars and earthing.

Characterisation of 10 kV 10 A SiC MOSFET

DEFF Research Database (Denmark)

Eni, Emanuel-Petre; Incau, Bogdan Ioan; Munk-Nielsen, Stig

2015-01-01

The objective of this paper is to characterize and evaluate the static and dynamic performances of 10 kV 10 A 4H-SIC MOSFETs at high temperatures. The results show good electrical performances of the SiC MOSFETs for high temperature operations. The double-pulse test results showed interesting...

KV7 potassium channels

DEFF Research Database (Denmark)

Stott, Jennifer B; Jepps, Thomas Andrew; Greenwood, Iain A

2014-01-01

Potassium channels are key regulators of smooth muscle tone, with increases in activity resulting in hyperpolarisation of the cell membrane, which acts to oppose vasoconstriction. Several potassium channels exist within smooth muscle, but the KV7 family of voltage-gated potassium channels have been...

Pathways toward understanding Macroscopic Quantum Phenomena

International Nuclear Information System (INIS)

Hu, B L; Subaşi, Y

2013-01-01

Macroscopic quantum phenomena refer to quantum features in objects of 'large' sizes, systems with many components or degrees of freedom, organized in some ways where they can be identified as macroscopic objects. This emerging field is ushered in by several categories of definitive experiments in superconductivity, electromechanical systems, Bose-Einstein condensates and others. Yet this new field which is rich in open issues at the foundation of quantum and statistical physics remains little explored theoretically (with the important exception of the work of A J Leggett [1], while touched upon or implied by several groups of authors represented in this conference. Our attitude differs in that we believe in the full validity of quantum mechanics stretching from the testable micro to meso scales, with no need for the introduction of new laws of physics.) This talk summarizes our thoughts in attempting a systematic investigation into some key foundational issues of quantum macroscopic phenomena, with the goal of ultimately revealing or building a viable theoretical framework. Three major themes discussed in three intended essays are the large N expansion [2], the correlation hierarchy [3] and quantum entanglement [4]. We give a sketch of the first two themes and then discuss several key issues in the consideration of macro and quantum, namely, a) recognition that there exist many levels of structure in a composite body and only by judicious choice of an appropriate set of collective variables can one give the best description of the dynamics of a specific level of structure. Capturing the quantum features of a macroscopic object is greatly facilitated by the existence and functioning of these collective variables; b) quantum entanglement, an exclusively quantum feature [5], is known to persist to high temperatures [6] and large scales [7] under certain conditions, and may actually decrease with increased connectivity in a quantum network [8]. We use entanglement as a

Regulation of KV channel voltage-dependent activation by transmembrane β subunits

Directory of Open Access Journals (Sweden)

Xiaohui eSun

2012-04-01

Full Text Available Voltage-activated K+ (KV channels are important for shaping action potentials and maintaining resting membrane potential in excitable cells. KV channels contain a central pore-gate domain (PGD surrounded by four voltage-sensing domains (VSD. The VSDs will change conformation in response to alterations of the membrane potential thereby inducing the opening of the PGD. Many KV channels are heteromeric protein complexes containing auxiliary β subunits. These β subunits modulate channel expression and activity to increase functional diversity and render tissue specific phenotypes. This review focuses on the KV β subunits that contain transmembrane (TM segments including the KCNE family and the β subunits of large conductance, Ca2+- and voltage-activated K+ (BK channels. These TM β subunits affect the voltage-dependent activation of KV α subunits. Experimental and computational studies have described the structural location of these β subunits in the channel complexes and the biophysical effects on VSD activation, PGD opening and VSD-PGD coupling. These results reveal some common characteristics and mechanistic insights into KV channel modulation by TM β subunits.

Improvement of the 400 kV linac electron source of AmPS

International Nuclear Information System (INIS)

Kroes, F.B.; Beuzekom, M.G. van; Dobbe, N.J.; Es, J.T. van; Jansweijer, P.P.M.; Kruijer, A.H.; Luigjes, G.; Sluijk, T.G.B.

1992-01-01

The installation of the 900 MeV Amsterdam Pulse Stretcher is nearly completed and its commissioning will start Spring 1992. The existing linac MEA will inject electrons in the AmPS ring. The linacs peak current will be increased from 20 to 80 mA. This requires modification of the 400 kV low emittance gun which now will deliver a peak current of maximum 400 mA instead of 100 mA at a pulse width of 2.1 μsec. The fourfold increase of the peakcurrent is obtained by doubling both the gun perveance (new gun part) and the pulsed extractor voltage. After chopping and pre-bunching more than 80 mA will be available for acceleration in MEA. To obtain optimum beam quality over this increased current range the hot deck electronics, operating at -400 kV, has been exchanged by a state of the art fast high voltage FET switching supply. The increased space charge forces in the beam require stronger electro-static focusing in the first electrostatic gap to define the beam diameter at the gun exit. This is accomplished with a 25 kV controlled power supply. A build in microprocessor, coupled to the local computer by optical fibers, is used to monitor and control the gun parameters. The 5kV gun extractor voltage pulse shape can be monitored by means of an analog fibre transducer with build in calibration. Finally, in order to improve the energy stability of the accelerated electrons a serial electron-tube stabilizer was added to the 400 kV DC power supply. A supply stability of 2. 10 -5 has been achieved. (author). 4 refs.; 6 figs

Remodeling of Kv1.5 channel in right atria from Han Chinese patients with atrial fibrillation.

Science.gov (United States)

Ou, Xian-hong; Li, Miao-ling; Liu, Rui; Fan, Xin-rong; Mao, Liang; Fan, Xue-hui; Yang, Yan; Zeng, Xiao-rong

2015-04-28

The incidence of atrial fibrillation (AF) in rheumatic heart diseases (RHD) is very high and increases with age. Occurrence and maintenance of AF are very complicated process accompanied by many different mechanisms. Ion-channel remodeling, including the voltage-gated potassium channel Kv1.5, plays an important role in the pathophysiology of AF. However, the changes of Kv1.5 channel expression in Han Chinese patients with RHD and AF remain poorly understood. The aim of the present study was to investigate whether the Kv1.5 channels of the right atria may be altered with RHD, age, and sex to contribute to AF. Right atrial appendages were obtained from 20 patients with normal cardiac functions who had undergone surgery, and 26 patients with AF. Subjects were picked from 4 groups: adult and aged patients in normal sinus rhythm (SR) and AF. Patients were divided into non-RHD and RHD groups or men and women groups in normal SR and AF, respectively. The expression of Kv1.5 protein and messenger RNA (mRNA) were measured using Western blotting and polymerase chain reaction (PCR) method, respectively. Compared with the SR group, the expression of Kv1.5 protein decreased significantly in the AF group. However, neither Kv1.5 protein nor KCNA5 mRNA had significant differences in adult and aged groups, non-RHD and RHD group, and men and women group of AF. The expression of Kv1.5 channel protein changes with AF but not with age, RHD, and sex in AF.

Analysis of the 35 KV substation secondary system

Science.gov (United States)

Zhao, Yong; Jiang, Jianguo; Jiang, Chunlei; Ren, Shuang; Liu, Songbin

2017-04-01

This paper analyzes the status of the two system of some 35KV users' substation in Daqing oil field, the deficiencies of the two system of the existing 35KV substation are found out. And put forward the opinion of acceptance in the future work. I hope it can able to work in the future on the protection of professional help.

Immunomodulatory effect of APS and PSP is mediated by Ca2+-cAMP and TLR4/NF-κB signaling pathway in macrophage.

Science.gov (United States)

Wang, Zhixue; Liu, Zijing; Zhou, Lijng; Long, Tingting; Zhou, Xing; Bao, Yixi

2017-01-01

This study is to investigate the role of second messengers and TLR4/NF-κB signaling pathway in the immunomodulatory activities of Astragalus polysaccharide (APS) and Polysaccharopeptide (PSP) in macrophages. RAW 264.7 macrophage cells were treated with APS, PSP, lipopolysaccharide (LPS), or NiCl 2 . Power-spectral method was used to detect protein kinase C (PKC) and Griess reaction to detect nitric oxide (NO). ELISA was conducted to detect cyclic adenosine monophosphate (cAMP), diglycerides (DAG), inositol 1, 4, 5-triphosphate (IP3), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Confocal laser scanning microscopy was performed to detect calcium level. qRT-PCR and Western blot was used to detect mRNA and protein expression of NF-κB. APS and PSP significantly increased the concentrations of intracellular second messengers (NO, cAMP, DAG, IP3, Ca 2+ ) and the activity of PKC in macrophages (pAPS and PSP (pAPS and PSP mediated immunomodulatory activities in macrophages. Copyright © 2016 Elsevier B.V. All rights reserved.

Fuel burn-up distribution and transuranic nuclide contents produced at the first cycle operation of AP1000

International Nuclear Information System (INIS)

Jati Susilo; Jupiter Sitorus Pane

2016-01-01

AP1000 reactor core was designed with nominal power of 1154 MWe (3415 MWth), operated within life time of 60 years and cycle length of 18 months. For the first cycle, the AP1000 core uses three kinds of UO 2 enrichment, they are 2.35 w/o, 3.40 w/o and 4.45 w/o. Absorber materials such as ZrB 2 , Pyrex and Boron solution are used to compensate the excess reactivity at the beginning of cycle. In the core, U-235 fuels are burned by fission reaction and produce energy, fission products and new neutron. Because of the U-238 neutron absorption reaction, the high level radioactive waste of heavy nuclide transuranic such as Pu, Am, Cm and Np are also generated. They have a very long half life. The purpose of this study is to evaluate the result of fuel burn-up distribution and heavy nuclide transuranic contents produced by AP1000 at the end of first cycle operation (EOFC). Calculation of ¼ part of the AP1000 core in the 2 dimensional model has been done using SRAC2006 code with the module of COREBN/HIST. The input data called the table of macroscopic cross section, is calculated using module of PIJ. The result shows that the maximum fuel assembly (FA) burn-up is 27.04 GWD/MTU, that is still lower than allowed maximum burn-up of 62 GWD/MTU. Fuel loading position at the center/middle of the core will produce bigger burn-up and transuranic nuclide than one at the edges the of the core. The use of IFBA fuel just give a small effect to lessen the fuel burn-up and transuranic nuclide production. (author)

Effect of the I(to) activator NS5806 on cloned K(V)4 channels depends on the accessory protein KChIP2

DEFF Research Database (Denmark)

Lundby, Alicia; Jespersen, Thomas; Schmitt, Nicole

2010-01-01

The compound NS5806 increases the transient outward current (I(to)) in canine ventricular cardiomyocytes and slows current decay. In human and canine ventricle, I(to) is thought to be mediated by K(V)4.3 and various ancillary proteins, yet, the exact subunit composition of I(to) channels is still...... debated. Here we characterize the effect of NS5806 on heterologously expressed putative I(to) channel subunits and other potassium channels....

Thermal Decomposition Characteristics of Orthorhombic Ammonium Perchlorate (o-AP) and an 0-AP/HTPB-Based Propellant

International Nuclear Information System (INIS)

BEHRENS JR., RICHARD; MINIER, LEANNA M.G.

1999-01-01

A study to characterize the low-temperature reactive processes for o-AP and an AP/HTPB-based propellant (class 1.3) is being conducted in the laboratory using the techniques of simultaneous thermogravimetric modulated beam mass spectrometry (STMBMS) and scanning electron microscopy (SEM). The results presented in this paper are a follow up of the previous work that showed the overall decomposition to be complex and controlled by both physical and chemical processes. The decomposition is characterized by the occurrence of one major event that consumes up to(approx)35% of the AP, depending upon particle size, and leaves behind a porous agglomerate of AP. The major gaseous products released during this event include H(sub 2)O, O(sub 2), Cl(sub 2), N(sub 2)O and HCl. The recent efforts provide further insight into the decomposition processes for o-AP. The temporal behaviors of the gas formation rates (GFRs) for the products indicate that the major decomposition event consists of three chemical channels. The first and third channels are affected by the pressure in the reaction cell and occur at the surface or in the gas phase above the surface of the AP particles. The second channel is not affected by pressure and accounts for the solid-phase reactions characteristic of o-AP. The third channel involves the interactions of the decomposition products with the surface of the AP. SEM images of partially decomposed o-AP provide insight to how the morphology changes as the decomposition progresses. A conceptual model has been developed, based upon the STMBMS and SEM results, that provides a basic description of the processes. The thermal decomposition characteristics of the propellant are evaluated from the identities of the products and the temporal behaviors of their GFRs. First, the volatile components in the propellant evolve from the propellant as it is heated. Second, the hot AP (and HClO(sub 4)) at the AP-binder interface oxidize the binder through reactions that

K významnému jubileu Květy Sgallové

Czech Academy of Sciences Publication Activity Database

Ibrahim, Robert

2009-01-01

Roč. 57, č. 4 (2009), s. 608-616 ISSN 0009-0468 Institutional research plan: CEZ:AV0Z90560517 Keywords : Sgallová, Květa * Czech literature * 19th century Subject RIV: AJ - Letters, Mass-media, Audiovision

Digital Control of a High Voltage (2.5 kV) Bidirectional Flyback DC-DC Converter for Driving a Capacitive Incremental Actuator

DEFF Research Database (Denmark)

Thummala, Prasanth; Maksimovic, Dragan; Zhang, Zhe

2016-01-01

This paper presents a digital control technique to achieve valley switching in a bidirectional flyback converter used to drive a dielectric electro-active polymer based capacitive incremental actuator. The paper also provides the design of a low input voltage (24 V) and variable high output voltage...... on the output high-voltage (HV) side. Experimental results verifying the bidirectional operation of a high voltage flyback converter are presented, using a 3 kV polypropylene film capacitor as the load. The energy loss distributions of the converter when 4 kV and 4.5 kV HV MOSFETs are used on HV side...

Improvement the Capacity of Cockcroft-Walton High Voltage Source from 300 kV/20 mA to 500 kV/20 mA for Accelerating Voltage of Electron Beam Machine

International Nuclear Information System (INIS)

Suprapto; Djasiman

2002-01-01

The improvement capacity of Cockcroft-Walton high voltage source from 300 kV/20 mA to 500 kV/mA has been carrying out. To improve the capacity of high voltage source was done by means of increasing the stage number of voltage multiplier from 11 to 18 and its output voltage measuring resistance. Each stage of voltage multiplier consists of 2 capacitors and 2 circuits of high voltage diode. This voltage multiplier is constructed using main components of high voltage capacitor and high voltage diode each of 0.22 μF/50 kV and UF 5408 respectively. To avoid stray discharge and corona it was provided with high voltage electrode and corona ring. The test result indicated that the output voltage obtained from 16 stages was 350 kV according to operating condition of 25 MΩ resistive load and first stage voltage of 28.5 kV with oscillator frequency of 24 Hz. That condition requires anode voltage and current of 5.5 kV and 2.5 A respectively. The no load test for 16 stages indicates 400 kV of output voltage and 28.5 kV first stage voltage. Efficiency of high voltage source was 48 % at 6.75 kW of output power. The expected test of 500 kV with 18 stages of voltage multiplier can not be carried out because of some restrictive of loading system. From the test result can be predicted that the output voltage of 500 kV with 18 stages of voltage multiplier requires 31.2 kV of first stage voltage. Then the expected high voltage source of Cockcroft-Walton is capable as accelerating voltage source for Electron Beam Machine with energy of 500 kV. (author)

Sci—Thur AM: YIS - 09: Validation of a General Empirically-Based Beam Model for kV X-ray Sources

Energy Technology Data Exchange (ETDEWEB)

Poirier, Y. [CancerCare Manitoba (Canada); University of Calgary (Canada); Sommerville, M.; Johnstone, C.D. [San Diego State University (United States); Gräfe, J.; Nygren, I.; Jacso, F. [Tom Baker Cancer Centre (Canada); Khan, R.; Villareal-Barajas, J.E. [University of Calgary (Canada); Tom Baker Cancer Centre (Canada); Tambasco, M. [University of Calgary (Canada); San Diego State University (United States)

2014-08-15

Purpose: To present an empirically-based beam model for computing dose deposited by kilovoltage (kV) x-rays and validate it for radiographic, CT, CBCT, superficial, and orthovoltage kV sources. Method and Materials: We modeled a wide variety of imaging (radiographic, CT, CBCT) and therapeutic (superficial, orthovoltage) kV x-ray sources. The model characterizes spatial variations of the fluence and spectrum independently. The spectrum is derived by matching measured values of the half value layer (HVL) and nominal peak potential (kVp) to computationally-derived spectra while the fluence is derived from in-air relative dose measurements. This model relies only on empirical values and requires no knowledge of proprietary source specifications or other theoretical aspects of the kV x-ray source. To validate the model, we compared measured doses to values computed using our previously validated in-house kV dose computation software, kVDoseCalc. The dose was measured in homogeneous and anthropomorphic phantoms using ionization chambers and LiF thermoluminescent detectors (TLDs), respectively. Results: The maximum difference between measured and computed dose measurements was within 2.6%, 3.6%, 2.0%, 4.8%, and 4.0% for the modeled radiographic, CT, CBCT, superficial, and the orthovoltage sources, respectively. In the anthropomorphic phantom, the computed CBCT dose generally agreed with TLD measurements, with an average difference and standard deviation ranging from 2.4 ± 6.0% to 5.7 ± 10.3% depending on the imaging technique. Most (42/62) measured TLD doses were within 10% of computed values. Conclusions: The proposed model can be used to accurately characterize a wide variety of kV x-ray sources using only empirical values.

Positioning errors assessed with kV cone-beam CT for image-guided prostate radiotherapy

International Nuclear Information System (INIS)

Li Jiongyan; Guo Xiaomao; Yao Weiqiang; Wang Yanyang; Ma Jinli; Chen Jiayi; Zhang Zhen; Feng Yan

2010-01-01

Objective: To assess set-up errors measured with kilovoltage cone-beam CT (KV-CBCT), and the impact of online corrections on margins required to account for set-up variability during IMRT for patients with prostate cancer. Methods: Seven patients with prostate cancer undergoing IMRT were enrolled onto the study. The KV-CBCT scans were acquired at least twice weekly. After initial set-up using the skin marks, a CBCT scan was acquired and registered with the planning CT to determine the setup errors using an auto grey-scale registration software. Corrections would be made by moving the table if the setup errors were considered clinically significant (i. e. , > 2 mm). A second CBCT scan was acquired immediately after the corrections to evaluate the residual error. PTV margins were derived to account for the measured set-up errors and residual errors determined for this group of patients. Results: 197 KV-CBCT images in total were acquired. The random and systematic positioning errors and calculated PTV margins without correction in mm were : a) Lateral 3.1, 2.1, 9.3; b) Longitudinal 1.5, 1.8, 5.1;c) Vertical 4.2, 3.7, 13.0. The random and systematic positioning errors and calculated PTV margin with correction in mm were : a) Lateral 1.1, 0.9, 3.4; b) Longitudinal 0.7, 1.1, 2.5; c) Vertical 1.1, 1.3, 3.7. Conclusions: With the guidance of online KV-CBCT, set-up errors could be reduced significantly for patients with prostate cancer receiving IMRT. The margin required after online CBCT correction for the patients enrolled in the study would be appoximatively 3-4 mm. (authors)

Partial characterization and response under hyperregulating conditions of Na+-K+ ATPase and levamisole-sensitive alkaline phosphatase activities in chela muscle of the euryhaline crab Cyrtograpsus angulatus

Directory of Open Access Journals (Sweden)

Silvina Andrea Pinoni

2008-03-01

Full Text Available The occurrence, characteristics and response to changes in environmental salinity of Na+-K+ ATPase and levamisole-sensitive alkaline phosphatase (AP activities were studied in chela muscle of the euryhaline crab Cyrtograpsus angulatus. Chela muscle exhibited an Na+-K+ ATPase activity which was strongly dependent on ATP concentration, pH and temperature of the reaction mixture. Maximal activity was found at 1 mM ATP, 30-37°C and pH 7.4. Levamisole-sensitive AP activity was characterised at physiological pH 7.4 and at pH 8.0. I50 for levamisole-sensitive AP activity was 8.8 mM and 8.0 mM at pH 7.4 and 8.0, respectively. At both pH levels, levamisole-sensitive AP activity exhibited Michaelis-Menten kinetics (Km=3.451 mM and 6.906 mM at pH 7.4 and 8.0, respectively. Levamisole-sensitive AP activities were strongly affected by temperature, exhibiting a peak at 37ºC. In crabs acclimated to low salinity (10; hyperegulating conditions, Na+-K+ ATPase activity and levamisole-sensitive AP activity at the physiological pH were higher than in 35 psu (osmoconforming conditions. The response to low salinity suggests that both activities could be components of muscle regulatory mechanisms at the biochemical level secondary to hyperegulation of C. angulatus. The study of these activities under hyperegulating conditions contributes to a better understanding of the complexity of biochemical mechanisms underlying the adaptive process of euryhaline crabs.

Numerical simulation of AP1000 LBLOCA with SCDAP/RELAP 4.0 code

International Nuclear Information System (INIS)

Xie Heng

2017-01-01

The risk of large-break loss of coolant accident (LBLOCA) is that core will be exposed once the accident occurs, and may cause core damages. New phenomena may occur in LBLOCA due to passive safety injection adopted by AP1000. This paper used SCDAP/RELAP5 4.0 to build the numerical model of AP1000 and double-end guillotine of cold leg is simulated. Reactor coolant system and passive core cooling system were modeled by RELAP5 modular. HEAT STRUCTURE component of RELAP5 was used to simulate the fuel rod. The reflood option in RELAP5 was chosen to be activated or not to study the effect of axial heat conduction. Results show that the axial heat conduction plays an important role in the reflooding phase and can effectively shorten reflood process. An alternative core model is built by SCDAP modular. It is found that the SCDAP model predicts higher maximum peak cladding temperature and longer reflood process than RELAP5 model. Analysis shows that clad oxidation heat plays a key role in the reflood. From the simulation results, it can be concluded that the cladding will keep intact and fission product will not be released from fuel to coolant in LBLOCA. (author)

The Voltage-Sensing Domain of K(v)7.2 Channels as a Molecular Target for Epilepsy-Causing Mutations and Anticonvulsants.

Science.gov (United States)

Miceli, Francesco; Soldovieri, Maria Virginia; Iannotti, Fabio Arturo; Barrese, Vincenzo; Ambrosino, Paolo; Martire, Maria; Cilio, Maria Roberta; Taglialatela, Maurizio

2011-01-01

Understanding the molecular mechanisms underlying voltage-dependent gating in voltage-gated ion channels (VGICs) has been a major effort over the last decades. In recent years, changes in the gating process have emerged as common denominators for several genetically determined channelopathies affecting heart rhythm (arrhythmias), neuronal excitability (epilepsy, pain), or skeletal muscle contraction (periodic paralysis). Moreover, gating changes appear as the main molecular mechanism by which several natural toxins from a variety of species affect ion channel function. In this work, we describe the pathophysiological and pharmacological relevance of the gating process in voltage-gated K(+) channels encoded by the K(v)7 gene family. After reviewing the current knowledge on the molecular mechanisms and on the structural models of voltage-dependent gating in VGICs, we describe the physiological relevance of these channels, with particular emphasis on those formed by K(v)7.2-K(v)7.5 subunits having a well-established role in controlling neuronal excitability in humans. In fact, genetically determined alterations in K(v)7.2 and K(v)7.3 genes are responsible for benign familial neonatal convulsions, a rare seizure disorder affecting newborns, and the pharmacological activation of K(v)7.2/3 channels can exert antiepileptic activity in humans. Both mutation-triggered channel dysfunction and drug-induced channel activation can occur by impeding or facilitating, respectively, channel sensitivity to membrane voltage and can affect overlapping molecular sites within the voltage-sensing domain of these channels. Thus, understanding the molecular steps involved in voltage-sensing in K(v)7 channels will allow to better define the pathogenesis of rare human epilepsy, and to design innovative pharmacological strategies for the treatment of epilepsies and, possibly, other human diseases characterized by neuronal hyperexcitability.

The effect of BAPTA and 4AP in scala media on transduction and cochlear gain.

Science.gov (United States)

Sellick, P M; Robertson, D; Patuzzi, R

2006-01-01

We have injected by iontophoresis 4-amino-pyridine, a K+ channel blocker and BAPTA, (a Ca++ chelator), into scala media of the first three turns of the guinea pig cochlea. We measured the reduction in outer hair cell (OHC) receptor current, as indicated by cochlear microphonic measured in scala media evoked by a 207 Hz tone, and compared this with the elevation of the cochlear action potential (CAP) threshold. We found that in the basal turn, for frequencies between 12 and 21 kHz, CAP threshold was elevated by about 30 dB, while in the second turn, at the 3 kHz place, the maximum elevation was 15 dB. In the third turn, iontophoresis of 4AP and BAPTA reduced CM by similar amounts to that in the basal and second turn, but caused negligible elevation of CAP threshold. We conclude that the gain of the cochlear amplifier is maximal for basal turn frequencies, is halved at 3 kHz, and is reduced to close to one for frequencies below 1 kHz (no active gain). The effect of 4AP and BAPTA on neural threshold and the receptor current represented by CM may be explained by their action on OHC transduction without the involvement of IHCs.

Automated tube voltage adaptation in head and neck computed tomography between 120 and 100 kV: effects on image quality and radiation dose

Energy Technology Data Exchange (ETDEWEB)

May, Matthias S.; Uder, Michael; Lell, Michael M. [University Hospital Erlangen, Department of Radiology, Erlangen (Germany); University Erlangen, Imaging Science Institute, Erlangen (Germany); Kramer, Manuel R.; Eller, Achim; Wuest, Wolfgang; Scharf, Michael; Brand, Michael; Saake, Marc [University Hospital Erlangen, Department of Radiology, Erlangen (Germany); Schmidt, Bernhard [Siemens Healthcare, Erlangen (Germany)

2014-09-15

Low tube voltage allows for computed tomography (CT) imaging with increased iodine contrast at reduced radiation dose. We sought to evaluate the image quality and potential dose reduction using a combination of attenuation based tube current modulation (TCM) and automated tube voltage adaptation (TVA) between 100 and 120 kV in CT of the head and neck. One hundred thirty consecutive patients with indication for head and neck CT were examined with a 128-slice system capable of TCM and TVA. Reference protocol was set at 120 kV. Tube voltage was reduced to 100 kV whenever proposed by automated analysis of the localizer. An additional small scan aligned to the jaw was performed at a fixed 120 kV setting. Image quality was assessed by two radiologists on a standardized Likert-scale and measurements of signal- (SNR) and contrast-to-noise ratio (CNR). Radiation dose was assessed as CTDI{sub vol}. Diagnostic image quality was excellent in both groups and did not differ significantly (p = 0.34). Image noise in the 100 kV data was increased and SNR decreased (17.8/9.6) in the jugular veins and the sternocleidomastoid muscle when compared to 120 kV (SNR 24.4/10.3), but not in fatty tissue and air. However, CNR did not differ statistically significant between 100 (23.5/14.4/9.4) and 120 kV data (24.2/15.3/8.6) while radiation dose was decreased by 7-8 %. TVA between 100 and 120 kV in combination with TCM led to a radiation dose reduction compared to TCM alone, while keeping CNR constant though maintaining diagnostic image quality. (orig.)

Retigabine, a Kv7.2/Kv7.3-Channel Opener, Attenuates Drug-Induced Seizures in Knock-In Mice Harboring Kcnq2 Mutations.

Science.gov (United States)

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.

Macroscopic constraints on string unification

International Nuclear Information System (INIS)

Taylor, T.R.

1989-03-01

The comparison of sting theory with experiment requires a huge extrapolation from the microscopic distances, of order of the Planck length, up to the macroscopic laboratory distances. The quantum effects give rise to large corrections to the macroscopic predictions of sting unification. I discus the model-independent constraints on the gravitational sector of string theory due to the inevitable existence of universal Fradkin-Tseytlin dilatons. 9 refs

Invariant methods for an ensemble-based sensitivity analysis of a passive containment cooling system of an AP1000 nuclear power plant

International Nuclear Information System (INIS)

Di Maio, Francesco; Nicola, Giancarlo; Borgonovo, Emanuele; Zio, Enrico

2016-01-01

Sensitivity Analysis (SA) is performed to gain fundamental insights on a system behavior that is usually reproduced by a model and to identify the most relevant input variables whose variations affect the system model functional response. For the reliability analysis of passive safety systems of Nuclear Power Plants (NPPs), models are Best Estimate (BE) Thermal Hydraulic (TH) codes, that predict the system functional response in normal and accidental conditions and, in this paper, an ensemble of three alternative invariant SA methods is innovatively set up for a SA on the TH code input variables. The ensemble aggregates the input variables raking orders provided by Pearson correlation ratio, Delta method and Beta method. The capability of the ensemble is shown on a BE–TH code of the Passive Containment Cooling System (PCCS) of an Advanced Pressurized water reactor AP1000, during a Loss Of Coolant Accident (LOCA), whose output probability density function (pdf) is approximated by a Finite Mixture Model (FMM), on the basis of a limited number of simulations. - Highlights: • We perform the reliability analysis of a passive safety system of Nuclear Power Plant (NPP). • We use a Thermal Hydraulic (TH) code for predicting the NPP response to accidents. • We propose an ensemble of Invariant Methods for the sensitivity analysis of the TH code • The ensemble aggregates the rankings of Pearson correlation, Delta and Beta methods. • The approach is tested on a Passive Containment Cooling System of an AP1000 NPP.

Berkeley Experiments on Superfluid Macroscopic Quantum Effects

International Nuclear Information System (INIS)

Packard, Richard

2006-01-01

This paper provides a brief history of the evolution of the Berkeley experiments on macroscopic quantum effects in superfluid helium. The narrative follows the evolution of the experiments proceeding from the detection of single vortex lines to vortex photography to quantized circulation in 3He to Josephson effects and superfluid gyroscopes in both 4He and 3He

Tank 241-AP-106, Grab samples, 6AP-98-1, 6AP-98-2 and 6AP-98-3 Analytical results for the final report

Energy Technology Data Exchange (ETDEWEB)

FULLER, R.K.

1999-02-23

This document is the final report for tank 241-AP-106 grab samples. Three grab samples 6AP-98-1, 6AP-98-2 and 6AP-98-3 were taken from riser 1 of tank 241-AP-106 on May 28, 1998 and received by the 222-S Laboratory on May 28, 1998. Analyses were performed in accordance with the ''Compatability Grab Sampling and Analysis Plan'' (TSAP) (Sasaki, 1998) and the ''Data Quality Objectives for Tank Farms Waste Compatability Program (DQO). The analytical results are presented in the data summary report. No notification limits were exceeded. The request for sample analysis received for AP-106 indicated that the samples were polychlorinated biphenyl (PCB) suspects. The results of this analysis indicated that no PCBs were present at the Toxic Substance Control Act (TSCA) regulated limit of 50 ppm. The results and raw data for the PCB analysis are included in this document.

Tank 241-AP-106, Grab samples, 6AP-98-1, 6AP-98-2 and 6AP-98-3 Analytical results for the final report

International Nuclear Information System (INIS)

FULLER, R.K.

1999-01-01

This document is the final report for tank 241-AP-106 grab samples. Three grab samples 6AP-98-1, 6AP-98-2 and 6AP-98-3 were taken from riser 1 of tank 241-AP-106 on May 28, 1998 and received by the 222-S Laboratory on May 28, 1998. Analyses were performed in accordance with the ''Compatability Grab Sampling and Analysis Plan'' (TSAP) (Sasaki, 1998) and the ''Data Quality Objectives for Tank Farms Waste Compatability Program (DQO). The analytical results are presented in the data summary report. No notification limits were exceeded. The request for sample analysis received for AP-106 indicated that the samples were polychlorinated biphenyl (PCB) suspects. The results of this analysis indicated that no PCBs were present at the Toxic Substance Control Act (TSCA) regulated limit of 50 ppm. The results and raw data for the PCB analysis are included in this document

Step-by-step application methodology in practical KEPCO 22.9kV bus-bar system

International Nuclear Information System (INIS)

Yoon, Jae-young; Lee, Seung-yeol

2010-01-01

With the increase of power demand and the progress of power industry deregulation, the transmission and distribution systems will have more complicated problems by the influence of curtailing investment and the NIMBY phenomena in overall power systems. [1-2] It is expected that the route length per MW demand of South Korea will decrease gradually from 0.6[C-km/MW] to 0.53[C-km/MW] in 2010.[3] This comes up to a real serious problem from system planning and operation viewpoints. HTS technologies related to power system have properties to solve these complex transmission and distribution constraints, especially for metropolitan area, in the future. As the HTS technology has developed, the HTS cable technology can be the most effective alternative to solve the future expected power network constraints. This paper describes the application methodology of developing 22.9kV HTS cable by CAST for practical distribution system. 22.9kV HTS cable under development with step-by-step application methodology can substitute the existing and planning conventional 154kV cable.[4-5] If this scheme is applied, part of downtown 154kV substation of metropolitan city such as Seoul can be changed into 22.9kV switching station. Additionally, it can give huge economic, environmental benefits to all of the concerned authorities.

Heteromeric Kv7.2/7.3 channels differentially regulate action potential initiation and conduction in neocortical myelinated axons.

Science.gov (United States)

Battefeld, Arne; Tran, Baouyen T; Gavrilis, Jason; Cooper, Edward C; Kole, Maarten H P

2014-03-05

Rapid energy-efficient signaling along vertebrate axons is achieved through intricate subcellular arrangements of voltage-gated ion channels and myelination. One recently appreciated example is the tight colocalization of K(v)7 potassium channels and voltage-gated sodium (Na(v)) channels in the axonal initial segment and nodes of Ranvier. The local biophysical properties of these K(v)7 channels and the functional impact of colocalization with Na(v) channels remain poorly understood. Here, we quantitatively examined K(v)7 channels in myelinated axons of rat neocortical pyramidal neurons using high-resolution confocal imaging and patch-clamp recording. K(v)7.2 and 7.3 immunoreactivity steeply increased within the distal two-thirds of the axon initial segment and was mirrored by the conductance density estimates, which increased from ~12 (proximal) to 150 pS μm(-2) (distal). The axonal initial segment and nodal M-currents were similar in voltage dependence and kinetics, carried by K(v)7.2/7.3 heterotetramers, 4% activated at the resting membrane potential and rapidly activated with single-exponential time constants (~15 ms at 28 mV). Experiments and computational modeling showed that while somatodendritic K(v)7 channels are strongly activated by the backpropagating action potential to attenuate the afterdepolarization and repetitive firing, axonal K(v)7 channels are minimally recruited by the forward-propagating action potential. Instead, in nodal domains K(v)7.2/7.3 channels were found to increase Na(v) channel availability and action potential amplitude by stabilizing the resting membrane potential. Thus, K(v)7 clustering near axonal Na(v) channels serves specific and context-dependent roles, both restraining initiation and enhancing conduction of the action potential.

Thrombotic risk assessment in APS: the Global APS Score (GAPSS).

Science.gov (United States)

Sciascia, S; Bertolaccini, M L

2014-10-01

Recently, we developed a risk score for antiphospholipid syndrome (APS) (Global APS Score or GAPSS). This score derived from the combination of independent risk factors for thrombosis and pregnancy loss, taking into account the antiphospholipid antibodies (aPL) profile (criteria and non-criteria aPL), the conventional cardiovascular risk factors, and the autoimmune antibodies profile. We demonstrate that risk profile in APS can be successfully assessed, suggesting that GAPSS can be a potential quantitative marker of APS-related clinical manifestations. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Development and use of 60 kV, and 150 kV floating deck modulators for high voltage protection of multi-megawatt ion beam accelerators

International Nuclear Information System (INIS)

Barber, G.C.; Ponte, N.S.; Schilling, G.

1977-01-01

Extraction currents of 60 A at 40 kV have been produced by utilizing a 60 kV floating deck modulator interfaced to a high voltage power supply. The modulator is operated in a series mode to repetitively pulse power to the ion beam accelerator. Current monitoring and other protective circuits provide interrupt commands to the series switch tube when faults occur. The constant current characteristics of the water cooled tetrode and the rapid response of the protective circuits effectively limit the fault energy to the ion source. Three of the 60 kV decks have been modified and stacked in a series configuration to supply 150 kV, 50 A pulses. This system supplies power for development of higher-energy multi-grid sources. In this system attention has been focused on forced voltage sharing of the three decks and on protective circuits for fault conditions. All control signal processing and conditioning is performed at ground level. Fiber optic links are used to interface with the high potential associated with the floating decks. A shunt modulator incorporated with this system provides regulation of the voltage to the ion source gradient grid. Future modulator development includes a system to deliver 100 A at 80 kV

Gold nanocatalyst-based immunosensing strategy accompanying catalytic reduction of 4-nitrophenol for sensitive monitoring of chloramphenicol residue.

Science.gov (United States)

Que, Xiaohua; Tang, Dianyong; Xia, Biyun; Lu, Minghua; Tang, Dianping

2014-06-09

A new competitive-type immunosensing system based on gold nanoparticles toward catalytic reduction of 4-nitrophenol (4-NP) was developed for sensitive monitoring of antibiotic residue (chloramphenicol, CAP, used in this case) by using ultraviolet-visible (UV-vis) spectrometry. Gold nanoparticle (AuNP) with 16 nm in diameter was initially synthesized and functionalized with CAP-bovine serum albumin (CAP-BSA) conjugate, which were used as the competitor on monoclonal anti-CAP antibody-coated polystyrene microtiter plate (MTP). In the presence of target CAP, the labeled CAP-BSA on the AuNP competed with target CAP for the immobilized antibody on the MTP. The conjugated amount of CAP-BSA-AuNP on the MTP decreased with the increase of target CAP in the sample. Upon addition of 4-NP and NaBH4 into the MTP, the carried AuNP could catalytically reduce 4-NP to 4-aminophenol (4-AP), and the as-produced 4-AP could be monitored by using UV-vis absorption spectroscopy. Experimental results indicated that the absorbance at 403 nm increased with the increment of target CAP concentration in the sample, and exhibited a dynamic range from 0.1 to 100 ng mL(-1) with a detection limit (LOD) of 0.03 ng mL(-1) at the 3s(blank) level. Intra- and inter-assay coefficients of variation were lower than 5.5% and 8.0%, respectively. In addition, the methodology was evaluated for CAP spiked honey and milk samples, respectively. The recovery was 92-112%. Copyright © 2014. Published by Elsevier B.V.

Performance of the 10-kV, 5-MA pulsed-power system for the FRX-C compression experiment

International Nuclear Information System (INIS)

Rej, D.J.; Waganaar, W.J.

1991-01-01

Performance data are presented for the 10-kV, 5-MA, 1.5-MJ pulsed-power system developed for the Los Alamos magnetic fusion facility FRX-C. This system energizes a low-inductance magnet for the high-power, compression heating of compact toroid plasmas. An ignitron-switched, 20-mF, 10-kV, 4-MA capacitor bank is discharged to produce the main compression field, while an inductively-isolated, 10-mF, 10-kV, 1-MA bank generates an initial magnetic field to accept the translated plasma. To date, the complete system has successfully operated for two years and approximately 2000 high-power discharges. Component performance during typical and fault-mode operation is reviewed. 5 refs., 5 figs

CONTRIBUTIONS OF INTRACELLULAR IONS TO Kv CHANNEL VOLTAGE SENSOR DYNAMICS.

Directory of Open Access Journals (Sweden)

Samuel eGoodchild

2012-06-01

Full Text Available Voltage sensing domains 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 voltage sensing domain caused by changes in the applied voltage across the membrane field are coupled to the conducting pore region and the gating of ionic conductance. 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.

Modulation of the transient outward current (Ito) in rat cardiac myocytes and human Kv4.3 channels by mefloquine

International Nuclear Information System (INIS)

Perez-Cortes, E.J.; Islas, A.A.; Arevalo, J.P.; Mancilla, C.; Monjaraz, E.; Salinas-Stefanon, E.M.

2015-01-01

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 (I to ) and the molecular correlate, the K v 4.3 channel has not being studied. Here, we describe the mefloquine-induced inhibition of the rat ventricular I to and of CHO cells co-transfected with human K v 4.3 and its accessory subunit hKChIP2C by whole-cell voltage-clamp. Mefloquine inhibited rat I to and hK v 4.3 + KChIP2C currents in a concentration-dependent manner with a limited voltage dependence and similar potencies (IC 50 = 8.9 μM and 10.5 μM for cardiac myocytes and K v 4.3 channels, respectively). In addition, mefloquine did not affect the activation of either current but significantly modified the hK v 4.3 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. - Highlights: • Mefloquine inhibited ventricular I to and hK v 4.3 channels. IC 50 = 8.9 and 10.5 μM. • Inactivation and recovery from inactivation in the hK v 4.3 channels were modified by mefloquine. • Mefloquine displayed a higher affinity for the inactivated state. • The binding site for mefloquine may be located in the extracellular side of the channel.

Deletion of the Kv2.1 delayed rectifier potassium channel leads to neuronal and behavioral hyperexcitability

Science.gov (United States)

Speca, David J.; Ogata, Genki; Mandikian, Danielle; Bishop, Hannah I.; Wiler, Steve W.; Eum, Kenneth; Wenzel, H. Jürgen; Doisy, Emily T.; Matt, Lucas; Campi, Katharine L.; Golub, Mari S.; Nerbonne, Jeanne M.; Hell, Johannes W.; Trainor, Brian C.; Sack, Jon T.; Schwartzkroin, Philip A.; Trimmer, James S.

2014-01-01

The Kv2.1 delayed rectifier potassium channel exhibits high-level expression in both principal and inhibitory neurons throughout the central nervous system, including prominent expression in hippocampal neurons. Studies of in vitro preparations suggest that Kv2.1 is a key yet conditional regulator of intrinsic neuronal excitability, mediated by changes in Kv2.1 expression, localization and function via activity-dependent regulation of Kv2.1 phosphorylation. Here we identify neurological and behavioral deficits in mutant (Kv2.1−/−) mice lacking this channel. Kv2.1−/− mice have grossly normal characteristics. No impairment in vision or motor coordination was apparent, although Kv2.1−/− mice exhibit reduced body weight. The anatomic structure and expression of related Kv channels in the brains of Kv2.1−/− mice appears unchanged. Delayed rectifier potassium current is diminished in hippocampal neurons cultured from Kv2.1−/− animals. Field recordings from hippocampal slices of Kv2.1−/− mice reveal hyperexcitability in response to the convulsant bicuculline, and epileptiform activity in response to stimulation. In Kv2.1−/− mice, long-term potentiation at the Schaffer collateral – CA1 synapse is decreased. Kv2.1−/− mice are strikingly hyperactive, and exhibit defects in spatial learning, failing to improve performance in a Morris Water Maze task. Kv2.1−/− mice are hypersensitive to the effects of the convulsants flurothyl and pilocarpine, consistent with a role for Kv2.1 as a conditional suppressor of neuronal activity. Although not prone to spontaneous seizures, Kv2.1−/− mice exhibit accelerated seizure progression. Together, these findings suggest homeostatic suppression of elevated neuronal activity by Kv2.1 plays a central role in regulating neuronal network function. PMID:24494598

Control of sulfate concentration by miR395-targeted APS genes in Arabidopsis thaliana

Directory of Open Access Journals (Sweden)

Qin Ai

2016-04-01

Full Text Available Sulfur nutrition is crucial for plant growth and development, as well as crop yield and quality. Inorganic sulfate in the soil is the major sulfur source for plants. After uptake, sulfate is activated by ATP sulfurylase, and then gets assimilated into sulfur-containing metabolites. However, the mechanism of regulation of sulfate levels by ATP sulfurylase is unclear. Here, we investigated the control of sulfate levels by miR395-mediated regulation of APS1/3/4. Sulfate was over-accumulated in the shoots of miR395 over-expression plants in which the expression of the APS1, APS3, and APS4 genes was suppressed. Accordingly, reduced expression of miR395 caused a decline of sulfate concentration. In agreement with these results, over-expression of the APS1, APS3, and APS4 genes led to the reduction of sulfate levels. Differential expression of these three APS genes in response to sulfate starvation implied that they have different functions. Further investigation revealed that the regulation of sulfate levels mediated by miR395 depends on the repression of its APS targets. Unlike the APS1, APS3, and APS4 genes, which encode plastid-localized ATP sulfurylases, the APS2 gene encodes a cytosolic version of ATP sulfurylase. Genetic analysis indicated that APS2 has no significant effect on sulfate levels. Our data suggest that miR395-targeted APS genes are key regulators of sulfate concentration in leaves.

The voltage-sensing domain of kv7.2 channels as a molecular target for epilepsy-causing mutations and anticonvulsants

Directory of Open Access Journals (Sweden)

Francesco eMiceli

2011-02-01

Full Text Available Understanding the molecular mechanisms underlying voltage-dependent gating in voltage-gated ion channels (VGICs has been a major effort over the last decades. In recent years, changes in the gating process have emerged as common denominators for several genetically-determined channelopathies affecting heart rhythm (arrhythmias, neuronal excitability (epilepsy, pain or skeletal muscle contraction (periodic paralysis. Moreover, gating changes appear as the main molecular mechanism by which several natural toxins from a variety of species affect ion channel function.In this work, we describe the pathophysiological and pharmacological relevance of the gating process in voltage-gated K+ channels encoded by the Kv7 gene family. After reviewing the current knowledge on the molecular mechanisms and on the structural models of voltage-dependent gating in VGICs, we describe the physiological relevance of these channels, with particular emphasis on those formed by Kv7.2-5 subunits having a well-established role in controlling neuronal excitability in humans. In fact, genetically-determined alterations in Kv7.2 and Kv7.3 genes are responsible for benign familial neonatal convulsions, a rare seizure disorder affecting newborns, and the pharmacological activation of Kv7.2/3 channels can exert antiepileptic activity in humans. Both mutation-triggered channel dysfunction and drug-induced channel activation can occur by impeding or facilitating, respectively, channel sensitivity to membrane voltage and can affect overlapping molecular sites within the voltage-sensing domain of these channels. Thus, understanding the molecular steps involved in voltage-sensing in Kv7 channels will allow to better define the pathogenesis of rare human epilepsy, and to design innovative pharmacological strategies for the treatment of epilepsies and, possibly, other human diseases characterized by neuronal hyperexcitability.

The development of a 200 kV monochromated field emission electron source

Energy Technology Data Exchange (ETDEWEB)

Mukai, Masaki, E-mail: mmukai@jeol.co.jp [JEOL Ltd., 3-1-2 Musashino, Akishima, Tokyo 196-8558 (Japan); Kim, Judy S. [University of Oxford, Department of Materials, Parks Road, Oxford, OX1 3PH (United Kingdom); Omoto, Kazuya; Sawada, Hidetaka; Kimura, Atsushi; Ikeda, Akihiro; Zhou, Jun; Kaneyama, Toshikatsu [JEOL Ltd., 3-1-2 Musashino, Akishima, Tokyo 196-8558 (Japan); Young, Neil P.; Warner, Jamie H.; Nellist, Peter D.; Kirkland, Angus I. [University of Oxford, Department of Materials, Parks Road, Oxford, OX1 3PH (United Kingdom)

2014-05-01

We report the development of a monochromator for an intermediate-voltage aberration-corrected electron microscope suitable for operation in both STEM and TEM imaging modes. The monochromator consists of two Wien filters with a variable energy selecting slit located between them and is located prior to the accelerator. The second filter cancels the energy dispersion produced by the first filter and after energy selection forms a round monochromated, achromatic probe at the specimen plane. The ultimate achievable energy resolution has been measured as 36 meV at 200 kV and 26 meV at 80 kV. High-resolution Annular Dark Field STEM images recorded using a monochromated probe resolve Si–Si spacings of 135.8 pm using energy spreads of 218 meV at 200 kV and 217 meV at 80 kV respectively. In TEM mode an improvement in non-linear spatial resolution to 64 pm due to the reduction in the effects of partial temporal coherence has been demonstrated using broad beam illumination with an energy spread of 134 meV at 200 kV. - Highlights: • Monochromator for 200 kV aberration corrected TEM and STEM was developed. • Monochromator produces monochromated and achromatic probe at specimen plane. • Ultimate energy resolution was measured to be 36 meV at 200 kV and 26 meV at 80 kV. • Atomic resolution STEM images were recorded using monochromated electron probe. • Improvements of TEM resolution were confirmed using monochromated illumination.

The development of a 200 kV monochromated field emission electron source

International Nuclear Information System (INIS)

Mukai, Masaki; Kim, Judy S.; Omoto, Kazuya; Sawada, Hidetaka; Kimura, Atsushi; Ikeda, Akihiro; Zhou, Jun; Kaneyama, Toshikatsu; Young, Neil P.; Warner, Jamie H.; Nellist, Peter D.; Kirkland, Angus I.

2014-01-01

We report the development of a monochromator for an intermediate-voltage aberration-corrected electron microscope suitable for operation in both STEM and TEM imaging modes. The monochromator consists of two Wien filters with a variable energy selecting slit located between them and is located prior to the accelerator. The second filter cancels the energy dispersion produced by the first filter and after energy selection forms a round monochromated, achromatic probe at the specimen plane. The ultimate achievable energy resolution has been measured as 36 meV at 200 kV and 26 meV at 80 kV. High-resolution Annular Dark Field STEM images recorded using a monochromated probe resolve Si–Si spacings of 135.8 pm using energy spreads of 218 meV at 200 kV and 217 meV at 80 kV respectively. In TEM mode an improvement in non-linear spatial resolution to 64 pm due to the reduction in the effects of partial temporal coherence has been demonstrated using broad beam illumination with an energy spread of 134 meV at 200 kV. - Highlights: • Monochromator for 200 kV aberration corrected TEM and STEM was developed. • Monochromator produces monochromated and achromatic probe at specimen plane. • Ultimate energy resolution was measured to be 36 meV at 200 kV and 26 meV at 80 kV. • Atomic resolution STEM images were recorded using monochromated electron probe. • Improvements of TEM resolution were confirmed using monochromated illumination

SU-F-J-54: Towards Real-Time Volumetric Imaging Using the Treatment Beam and KV Beam

Energy Technology Data Exchange (ETDEWEB)

Chen, M; Rozario, T; Liu, A; Jiang, S; Lu, W [UT Southwestern Medical Center, Dallas, TX (United States)

2016-06-15

Purpose: Existing real-time imaging uses dual (orthogonal) kV beam fluoroscopies and may result in significant amount of extra radiation to patients, especially for prolonged treatment cases. In addition, kV projections only provide 2D information, which is insufficient for in vivo dose reconstruction. We propose real-time volumetric imaging using prior knowledge of pre-treatment 4D images and real-time 2D transit data of treatment beam and kV beam. Methods: The pre-treatment multi-snapshot volumetric images are used to simulate 2D projections of both the treatment beam and kV beam, respectively, for each treatment field defined by the control point. During radiation delivery, the transit signals acquired by the electronic portal image device (EPID) are processed for every projection and compared with pre-calculation by cross-correlation for phase matching and thus 3D snapshot identification or real-time volumetric imaging. The data processing involves taking logarithmic ratios of EPID signals with respect to the air scan to reduce modeling uncertainties in head scatter fluence and EPID response. Simulated 2D projections are also used to pre-calculate confidence levels in phase matching. Treatment beam projections that have a low confidence level either in pre-calculation or real-time acquisition will trigger kV beams so that complementary information can be exploited. In case both the treatment beam and kV beam return low confidence in phase matching, a predicted phase based on linear regression will be generated. Results: Simulation studies indicated treatment beams provide sufficient confidence in phase matching for most cases. At times of low confidence from treatment beams, kV imaging provides sufficient confidence in phase matching due to its complementary configuration. Conclusion: The proposed real-time volumetric imaging utilizes the treatment beam and triggers kV beams for complementary information when the treatment beam along does not provide sufficient

Models for universal reduction of macroscopic quantum fluctuations

International Nuclear Information System (INIS)

Diosi, L.

1988-10-01

If quantum mechanics is universal, then macroscopic bodies would, in principle, possess macroscopic quantum fluctuations (MQF) in their positions, orientations, densities etc. Such MQF, however, are not observed in nature. The hypothesis is adopted that the absence of MQF is due to a certain universal mechanism. Gravitational measures were applied for reducing MQF of the mass density. This model leads to classical trajectories in the macroscopic limit of translational motion. For massive objects, unwanted macroscopic superpositions of quantum states will be destroyed within short times. (R.P.) 34 refs

Upgrade of a 30 kV/10 mA anode power supply for triode type gyrotron

Energy Technology Data Exchange (ETDEWEB)

Siravo, Ugo, E-mail: ugo.siravo@epfl.ch; Alberti, Stefano; Dubray, Jérémie; Fasel, Damien; Hogge, Jean-Philippe; Marlétaz, Blaise; Marmillod, Philippe; Perez, Albert; Silva, Miguel

2015-10-15

Highlights: • Triode type gyrotron is fed by 3 power supplies: the main, an anode PS(APS) and a heater. • This paper presents the upgrade of 3APS, supplied in 1999, that never fulfilled the specs. • The new working principle is very efficient, easy to implement, for a minimal cost. • Upgraded APS provides extended modulation capabilities, no overshoot and lowerripple. • This upgrade will allow exploring new operation regimes for the 3 TCV X3 gyrotrons. - The RF power of a gyrotron with a triode type magnetron-injection-gun (MIG) can be directly controlled via the voltage applied between its anode and its cathode. Hence, the performance of this type of gyrotron relies directly on the possibilities offered by the power supply controlling the anode to cathode voltage. For a system of gyrotrons connected to the same main high-voltage power supply, with a triode MIG one has the additional advantage of independently controlling each individual gyrotron. This paper presents the modifications brought to the three existing 30 kV/10 mA anode power supplies connected to the 500 kW/118 GHz/2s X3 gyrotrons operated on the TCV Tokamak. The new working principle based on phase-shift modulation (PSM) is described in detail. Experimental results obtained on dummy load are compared to simulations performed during the design phase. With respect to the initial working principle, the modulation frequency capability has been increased by a factor 10 reaching more than 5 kHz, whereas the output voltage ripple as well as the overshoot/undershoot have been significantly reduced.

[Traditional risk factors for cardiovascular disease in primary antiphospholipid syndrome (APS) when compared with secondary APS: a study with 96 patients].

Science.gov (United States)

Ribeiro, A R; Carvalho, J F

2010-01-01

To evaluate the prevalence of traditional risk factors in patients with primary antiphospholipid syndrome (APS) in comparison to those with systemic lupus erythematosus-secondary APS. Transversal study of 96 APS patients (Sapporo's criteria). Demographic and clinical data, cardiovascular risk factors and drug use were investigated. Thirty-nine Primary APS and 57 secondary APS were included. The groups did not differ regarding age (38.5 +/- 9.9 vs. 39.4 +/- 10.5 years, p=0.84) and female gender (84.6 vs. 96.5%, p=0.06), respectively. Arterial events were more observed in primary than secondary APS (59 vs. 36.8%, p=0.04) patients. No difference was seen concerning venous and obstetric events. In regard to traditional risk factors for cardiovascular disease, both groups were comparable related to current or previous smoking, sedentarism, family history for coronary disease, systemic hypertension, diabetes mellitus, overweight and obesity. The frequencies of altered lipid profiles were alike in the two groups, except for a higher prevalence of low HDL-c levels in primary APS group (84.6 vs. 45.5%, p=0.0001). Concerning drug use, no significant differences were observed related to chloroquine and statin use, however the secondary APS patients had a higher rate of prednisone use (10.2 vs. 57.9%, pAPS, except for a high frequency of low HDL-c in primary APS patients.

APS Science 2006

International Nuclear Information System (INIS)

Gibson, J.M.; Fenner, R.B.; Long, G.; Borland, M.; Decker, G.

2007-01-01

In my five years as the Director of the Advanced Photon Source (APS), I have been fortunate to see major growth in the scientific impact from the APS. This year I am particularly enthusiastic about prospects for our longer-term future. Every scientific instrument must remain at the cutting edge to flourish. Our plans for the next generation of APS--an APS upgrade--got seriously in gear this year with strong encouragement from our users and sponsors. The most promising avenue that has emerged is the energy-recovery linac (ERL) (see article on page xx), for which we are beginning serious R and D. The ERL(at)APS would offer revolutionary performance, especially for x-ray imaging and ultrafast science, while not seriously disrupting the existing user base. I am very proud of our accelerator physics and engineering staff, who not only keep the current APS at the forefront, but were able to greatly impress our international Machine Advisory Committee with the quality of their work on the possible upgrade option (see page xx). As we prepare for long-term major upgrades, our plans to develop and optimize all the sectors at APS in the near future are advancing. Several new beamlines saw first light this year, including a dedicated powder diffraction beamline (11-BM), two instruments for inelastic x-ray scattering at sector 30, and the Center for Nanoscale Materials (CNM) Nanoprobe beamline at sector 26. Our partnership in the first x-ray free-electron laser (LCLS) to be built at Stanford contributes to revolutionary growth in ultrafast science (see page xx), and we are developing a pulse chirping scheme to get ps pulses at sector 7 of the APS within a year or so. In this report, you will find selected highlights of scientific research at the APS from calendar year 2006. The highlighted work covers diverse disciplines, from fundamental to applied science. In the article on page xx you can see the direct impact of APS research on technology. Several new products have emerged

APS Science 2006.

Energy Technology Data Exchange (ETDEWEB)

Gibson, J. M.; Fenner, R. B.; Long, G.; Borland, M.; Decker, G.

2007-05-24

In my five years as the Director of the Advanced Photon Source (APS), I have been fortunate to see major growth in the scientific impact from the APS. This year I am particularly enthusiastic about prospects for our longer-term future. Every scientific instrument must remain at the cutting edge to flourish. Our plans for the next generation of APS--an APS upgrade--got seriously in gear this year with strong encouragement from our users and sponsors. The most promising avenue that has emerged is the energy-recovery linac (ERL) (see article on page xx), for which we are beginning serious R&D. The ERL{at}APS would offer revolutionary performance, especially for x-ray imaging and ultrafast science, while not seriously disrupting the existing user base. I am very proud of our accelerator physics and engineering staff, who not only keep the current APS at the forefront, but were able to greatly impress our international Machine Advisory Committee with the quality of their work on the possible upgrade option (see page xx). As we prepare for long-term major upgrades, our plans to develop and optimize all the sectors at APS in the near future are advancing. Several new beamlines saw first light this year, including a dedicated powder diffraction beamline (11-BM), two instruments for inelastic x-ray scattering at sector 30, and the Center for Nanoscale Materials (CNM) Nanoprobe beamline at sector 26. Our partnership in the first x-ray free-electron laser (LCLS) to be built at Stanford contributes to revolutionary growth in ultrafast science (see page xx), and we are developing a pulse chirping scheme to get ps pulses at sector 7 of the APS within a year or so. In this report, you will find selected highlights of scientific research at the APS from calendar year 2006. The highlighted work covers diverse disciplines, from fundamental to applied science. In the article on page xx you can see the direct impact of APS research on technology. Several new products have emerged from

Interpretation of macroscopic quantum phenomena

International Nuclear Information System (INIS)

Baumann, K.

1986-01-01

It is argued that a quantum theory without observer is required for the interpretation of macroscopic quantum tunnelling. Such a theory is obtained by augmenting QED by the actual electric field in the rest system of the universe. An equation of the motion of this field is formulated form which the correct macroscopic behavior of the universe and the validity of the Born interpretation is derived. Care is taken to use mathematically sound concepts only. (Author)

Superposition and macroscopic observation

International Nuclear Information System (INIS)

Cartwright, N.D.

1976-01-01

The principle of superposition has long plagued the quantum mechanics of macroscopic bodies. In at least one well-known situation - that of measurement - quantum mechanics predicts a superposition. It is customary to try to reconcile macroscopic reality and quantum mechanics by reducing the superposition to a mixture. To establish consistency with quantum mechanics, values for the apparatus after a measurement are to be distributed in the way predicted by the superposition. The distributions observed, however, are those of the mixture. The statistical predictions of quantum mechanics, it appears, are not borne out by observation in macroscopic situations. It has been shown that, insofar as specific ergodic hypotheses apply to the apparatus after the interaction, the superposition which evolves is experimentally indistinguishable from the corresponding mixture. In this paper an idealized model of the measuring situation is presented in which this consistency can be demonstrated. It includes a simplified version of the measurement solution proposed by Daneri, Loinger, and Prosperi (1962). The model should make clear the kind of statistical evidence required to carry of this approach, and the role of the ergodic hypotheses assumed. (Auth.)

Macroscopic theory of superconductors

International Nuclear Information System (INIS)

Carr, W.J. Jr.

1981-01-01

A macroscopic theory for bulk superconductors is developed in the framework of the theory for other magnetic materials, where ''magnetization'' current is separated from ''free'' current on the basis of scale. This contrasts with the usual separation into equilibrium and nonequilibrium currents. In the present approach magnetization, on a large macroscopic scale, results from the vortex current, while the Meissner current and other surface currents are surface contributions to the Maxwell j. The results are important for the development of thermodynamics in type-II superconductors. The advantage of the description developed here is that magnetization becomes a local concept and its associated magnetic field can be given physical meaning

Kv7.1 surface expression is regulated by epithelial cell polarization

DEFF Research Database (Denmark)

Andersen, Martin N; Olesen, Søren-Peter; Rasmussen, Hanne Borger

2011-01-01

The potassium channel K(V)7.1 is expressed in the heart where it contributes to the repolarization of the cardiac action potential. In addition, K(V)7.1 is expressed in epithelial tissues where it plays a role in salt and water transport. Mutations in the kcnq1 gene can lead to long QT syndrome...... and deafness, and several mutations have been described as trafficking mutations. To learn more about the basic mechanisms that regulate K(V)7.1 surface expression, we have investigated the trafficking of K(V)7.1 during the polarization process of the epithelial cell line Madin-Darby Canine Kidney (MDCK) using...... is regulated by signaling mechanisms involved in epithelial cell polarization in particular signaling cascades involving protein kinase C and PI3K....

The secret life of ion channels: Kv1.3 potassium channels and proliferation.

Science.gov (United States)

Pérez-García, M Teresa; Cidad, Pilar; López-López, José R

2018-01-01

Kv1.3 channels are involved in the switch to proliferation of normally quiescent cells, being implicated in the control of cell cycle in many different cell types and in many different ways. They modulate membrane potential controlling K + fluxes, sense changes in potential, and interact with many signaling molecules through their intracellular domains. From a mechanistic point of view, we can describe the role of Kv1.3 channels in proliferation with at least three different models. In the "membrane potential model," membrane hyperpolarization resulting from Kv1.3 activation provides the driving force for Ca 2+ influx required to activate Ca 2+ -dependent transcription. This model explains most of the data obtained from several cells from the immune system. In the "voltage sensor model," Kv1.3 channels serve mainly as sensors that transduce electrical signals into biochemical cascades, independently of their effect on membrane potential. Kv1.3-dependent proliferation of vascular smooth muscle cells (VSMCs) could fit this model. Finally, in the "channelosome balance model," the master switch determining proliferation may be related to the control of the Kv1.3 to Kv1.5 ratio, as described in glial cells and also in VSMCs. Since the three mechanisms cannot function independently, these models are obviously not exclusive. Nevertheless, they could be exploited differentially in different cells and tissues. This large functional flexibility of Kv1.3 channels surely gives a new perspective on their functions beyond their elementary role as ion channels, although a conclusive picture of the mechanisms involved in Kv1.3 signaling to proliferation is yet to be reached.

Blockade of the voltage-gated potassium channel Kv1.3 inhibits immune responses in vivo.

Science.gov (United States)

Koo, G C; Blake, J T; Talento, A; Nguyen, M; Lin, S; Sirotina, A; Shah, K; Mulvany, K; Hora, D; Cunningham, P; Wunderler, D L; McManus, O B; Slaughter, R; Bugianesi, R; Felix, J; Garcia, M; Williamson, J; Kaczorowski, G; Sigal, N H; Springer, M S; Feeney, W

1997-06-01

The voltage activated K+ channel (Kv1.3) has recently been identified as the molecule that sets the resting membrane potential of peripheral human T lymphoid cells. In vitro studies indicate that blockage of Kv1.3 inhibits T cell activation, suggesting that Kv1.3 may be a target for immunosuppression. However, despite the in vitro evidence, there has been no in vivo demonstration that blockade of Kv1.3 will attenuate an immune response. The difficulty is due to species differences, as the channel does not set the membrane potential in rodent peripheral T cells. In this study, we show that the channel is present on peripheral T cells of miniswine. Using the peptidyl Kv1.3 inhibitor, margatoxin, we demonstrate that Kv1.3 also regulates the resting membrane potential, and that blockade of Kv1.3 inhibits, in vivo, both a delayed-type hypersensitivity reaction and an Ab response to an allogeneic challenge. In addition, prolonged Kv1.3 blockade causes reduced thymic cellularity and inhibits the thymic development of T cell subsets. These results provide in vivo evidence that Kv1.3 is a novel target for immunomodulation.

PKC and AMPK regulation of Kv1.5 potassium channels

DEFF Research Database (Denmark)

Andersen, Martin Nybo; Skibsbye, Lasse; Tang, Chuyi

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....

Optical triggering of 4H-SiC thyristors (18 kV class) to high currents in purely inductive load circuit

International Nuclear Information System (INIS)

Rumyantsev, S L; Levinshtein, M E; Saxena, T; Shur, M S; Cheng, L; Palmour, J W; Agarwal, A

2014-01-01

Optical switch-on of a very high voltage (18 kV class) 4H-SiC thyristor with an amplification step (pilot thyristor) to the current I max  = 1225 A is demonstrated using a purely inductive load and a calibrated air transformer. Increasing the inductance of the transformer primary winding slows down the turn on process. However, the inductance has little effect during the initial stage of the switch-on process when the voltage drop on the thyristor and its internal resistance is high. The results show that a further switch-on current increase can be only achieved by introducing additional amplification steps in the pilot thyristor. (paper)

Residual translational and rotational errors after kV X-ray image-guided correction of prostate location using implanted fiducials

International Nuclear Information System (INIS)

Wust, Peter; Graf, Reinhold; Boehmer, Dirk; Budach, Volker

2010-01-01

Purpose: To evaluate the residual errors and required safety margins after stereoscopic kilovoltage (kV) X-ray target localization of the prostate in image-guided radiotherapy (IGRT) using internal fiducials. Patients and Methods: Radiopaque fiducial markers (FMs) have been inserted into the prostate in a cohort of 33 patients. The ExacTrac/Novalis Body trademark X-ray 6d image acquisition system (BrainLAB AG, Feldkirchen, Germany) was used. Corrections were performed in left-right (LR), anterior-posterior (AP), and superior-inferior (SI) direction. Rotational errors around LR (x-axis), AP (y) and SI (z) have been recorded for the first series of nine patients, and since 2007 for the subsequent 24 patients in addition corrected in each fraction by using the Robotic Tilt Module trademark and Varian Exact Couch trademark. After positioning, a second set of X-ray images was acquired for verification purposes. Residual errors were registered and again corrected. Results: Standard deviations (SD) of residual translational random errors in LR, AP, and SI coordinates were 1.3, 1.7, and 2.2 mm. Residual random rotation errors were found for lateral (around x, tilt), vertical (around y, table), and longitudinal (around z, roll) and of 3.2 , 1.8 , and 1.5 . Planning target volume (PTV)-clinical target volume (CTV) margins were calculated in LR, AP, and SI direction to 2.3, 3.0, and 3.7 mm. After a second repositioning, the margins could be reduced to 1.8, 2.1, and 1.8 mm. Conclusion: On the basis of the residual setup error measurements, the margin required after one to two online X-ray corrections for the patients enrolled in this study would be at minimum 2 mm. The contribution of intrafractional motion to residual random errors has to be evaluated. (orig.)

Residual translational and rotational errors after kV X-ray image-guided correction of prostate location using implanted fiducials

Energy Technology Data Exchange (ETDEWEB)

Wust, Peter [Dept. of Radiation Oncology, Charite - Univ. Medicine Berlin, Campus Virchow-Klinikum, Berlin (Germany); Graf, Reinhold; Boehmer, Dirk; Budach, Volker

2010-10-15

Purpose: To evaluate the residual errors and required safety margins after stereoscopic kilovoltage (kV) X-ray target localization of the prostate in image-guided radiotherapy (IGRT) using internal fiducials. Patients and Methods: Radiopaque fiducial markers (FMs) have been inserted into the prostate in a cohort of 33 patients. The ExacTrac/Novalis Body trademark X-ray 6d image acquisition system (BrainLAB AG, Feldkirchen, Germany) was used. Corrections were performed in left-right (LR), anterior-posterior (AP), and superior-inferior (SI) direction. Rotational errors around LR (x-axis), AP (y) and SI (z) have been recorded for the first series of nine patients, and since 2007 for the subsequent 24 patients in addition corrected in each fraction by using the Robotic Tilt Module trademark and Varian Exact Couch trademark. After positioning, a second set of X-ray images was acquired for verification purposes. Residual errors were registered and again corrected. Results: Standard deviations (SD) of residual translational random errors in LR, AP, and SI coordinates were 1.3, 1.7, and 2.2 mm. Residual random rotation errors were found for lateral (around x, tilt), vertical (around y, table), and longitudinal (around z, roll) and of 3.2 , 1.8 , and 1.5 . Planning target volume (PTV)-clinical target volume (CTV) margins were calculated in LR, AP, and SI direction to 2.3, 3.0, and 3.7 mm. After a second repositioning, the margins could be reduced to 1.8, 2.1, and 1.8 mm. Conclusion: On the basis of the residual setup error measurements, the margin required after one to two online X-ray corrections for the patients enrolled in this study would be at minimum 2 mm. The contribution of intrafractional motion to residual random errors has to be evaluated. (orig.)

Experimental demonstration of macroscopic quantum coherence in Gaussian states

DEFF Research Database (Denmark)

Marquardt, C.; Andersen, Ulrik Lund; Leuchs, G.

2007-01-01

We witness experimentally the presence of macroscopic coherence in Gaussian quantum states using a recently proposed criterion [E. G. Cavalcanti and M. D. Reid, Phys. Rev. Lett. 97 170405 (2006)]. The macroscopic coherence stems from interference between macroscopically distinct states in phase...

Testing of Solar Heated Domestic Hot Water System for Solahart Scandinavia ApS

DEFF Research Database (Denmark)

Andersen, Elsa

1997-01-01

The solar heating system marketed by Solahart Scandinavia ApS was tested in the Institutes test facility for SDHWsystems. The test results are described in the report.......The solar heating system marketed by Solahart Scandinavia ApS was tested in the Institutes test facility for SDHWsystems. The test results are described in the report....

Sialic acid-triggered macroscopic properties switching on a smart polymer surface

Science.gov (United States)

Xiong, Yuting; Li, Minmin; Wang, Hongxi; Qing, Guangyan; Sun, Taolei

2018-01-01

Constructing smart surfaces with responsive polymers capable of dynamically and reversibly changing their chemical and physical properties by responding to the recognition of biomolecules remains a challenging task. And, the key to achieving this purpose relies on the design of polymers to precisely interact with the target molecule and successfully transform the interaction signal into tunable macroscopic properties, further achieve special bio-functions. Herein, inspired by carbohydrate-carbohydrate interaction (CCI) in life system, we developed a three-component copolymer poly(NIPAAm-co-PT-co-Glc) bearing a binding unit glucose (Glc) capable of recognizing sialic acid, a type of important molecular targets for cancer diagnosis and therapy, and reported the sialic acid triggered macroscopic properties switching on this smart polymer surface. Detailed mechanism studies indicated that multiple hydrogen bonding interactions between Glc unit and Neu5Ac destroyed the initial hydrogen bond network of the copolymer, leading to a reversible "contraction-to-swelling" conformational transition of the copolymer chains, accompanied with distinct macroscopic property switching (i.e., surface wettability, morphology, stiffness) of the copolymer film. And these features enabled this copolymer to selectively capture sialic acid-containing glycopeptides from complex protein samples. This work provides an inspiration for the design of novel smart polymeric materials with sensitive responsiveness to sialic acid, which would promote the development of sialic acid-specific bio-devices and drug delivery systems.

A Common Structural Component for β-Subunit Mediated Modulation of Slow Inactivation in Different KV Channels

Directory of Open Access Journals (Sweden)

Nathalie Strutz-Seebohm

2013-06-01

Full Text Available Background/Aims: Potassium channels are tetrameric proteins providing potassium selective passage through lipid embedded proteinaceous pores with highest fidelity. The selectivity results from binding to discrete potassium binding sites and stabilization of a hydrated potassium ion in a central internal cavity. The four potassium binding sites, generated by the conserved TTxGYGD signature sequence are formed by the backbone carbonyls of the amino acids TXGYG. Residues KV1.5-Val481, KV4.3-Leu368 and KV7.1- Ile 313 represent the amino acids in the X position of the respective channels. Methods: Here, we study the impact of these residues on ion selectivity, permeation and inactivation kinetics as well as the modulation by β-subunits using site-specific mutagenesis, electrophysiological analyses and molecular dynamics simulations. Results: We identify this position as key in modulation of slow inactivation by structurally dissimilar β-subunits in different KV channels. Conclusion: We propose a model in which structural changes accompanying activation and β-subunit modulation allosterically constrain the backbone carbonyl oxygen atoms via the side chain of the respective X-residue in the signature sequence to reduce conductance during slow inactivation.

Macroscopic optical response and photonic bands

International Nuclear Information System (INIS)

Pérez-Huerta, J S; Luis Mochán, W; Ortiz, Guillermo P; Mendoza, Bernardo S

2013-01-01

We develop a formalism for the calculation of the macroscopic dielectric response of composite systems made of particles of one material embedded periodically within a matrix of another material, each of which is characterized by a well-defined dielectric function. The nature of these dielectric functions is arbitrary, and could correspond to dielectric or conducting, transparent or opaque, absorptive and dispersive materials. The geometry of the particles and the Bravais lattice of the composite are also arbitrary. Our formalism goes beyond the long-wavelength approximation as it fully incorporates retardation effects. We test our formalism through the study of the propagation of electromagnetic waves in two-dimensional photonic crystals made of periodic arrays of cylindrical holes in a dispersionless dielectric host. Our macroscopic theory yields a spatially dispersive macroscopic response which allows the calculation of the full photonic band structure of the system, as well as the characterization of its normal modes, upon substitution into the macroscopic field equations. We can also account approximately for the spatial dispersion through a local magnetic permeability and analyze the resulting dispersion relation, obtaining a region of left handedness. (paper)

Quality control of a kV cone beam computed tomography imaging system

International Nuclear Information System (INIS)

Marguet, M.; Bodez, V.

2009-01-01

Purpose: This work presents the introduction of a quality assurance program for the On-Board Imager (O.B.I., Varian) kV cone beam computed tomography (kV C.B.C.T.) system, together with the results of 1 year monthly testing. Materials and methods: Firstly the geometric precision and stability of the equipment and of the associated software were evaluated using the Marker phantom. The coincidence of the accelerator isocenter and the imager isocenter was verified as well as the accuracy of the registration of kV cone beam computed tomography (kV C.B.C.T.) with reference CT images. Then, the kV C.B.C.T. image quality was evaluated using the Catphan 504 phantom and ArtiScan software (Aquilab) for both full-fan (F.F.) and half-fan (H.F.) imaging modes. Results: The kV C.B.C.T. isocenter and image registration with correction of the table position were found to be within a tolerance of 2.0 mm. Concerning the kV C.B.C.T. image quality, image noise and uniformity, the Hounsfield units (HU) stability and linearity, geometric distortion and high contrast resolution were all found to be within the manufacturer's recommendations for both F.F. and H.F. modes. However, the low contrast resolution for the HF mode did not meet the manufacturer's specifications. Conclusion: The quality assurance tests introduced have defined the initial system characteristics and their evolution during a period of 1 year, demonstrating the stability of the O.B.I.. (authors)

Comparison of Spectral and Scintillation Properties of LuAP:Ce and LuAP:Ce,Sc Single Crystals

Science.gov (United States)

Petrosyan, Ashot G.; Derdzyan, Marina; Ovanesyan, Karine; Shirinyan, Grigori; Lecoq, Paul; Auffray, Etiennette; Kronberger, Matthias; Frisch, Benjamin; Pedrini, Christian; Dujardin, Christophe

2009-10-01

Scintillation properties of LuAP:Ce and LuAP:Ce,Sc crystal series were studied under excitation by gamma-rays from a 137Cs source. Both series demonstrated comparable optical quality in terms of underlying absorption at 260 nm, slope of the optical edge and transmission in the range of emission. The light yield of LuAP:Ce crystals measured in 0.2 cm times 0.2 cm times 0.8 cm pixels increases linearly with the Ce concentration reaching at 0.58 at. % 6448 plusmn 322 ph/MeV and 9911 plusmn 496 ph/MeV in the long and in the short directions respectively (the light yield ratio is 65%) and shows no sign of light saturation. The energy resolution is found to depend, among other factors, on the uniformity of Ce concentration within the pixels and is improved to 7.1 plusmn 0.4% (I = 0.2 cm), 9.5 plusmn 0.5% (I = 0.8 cm). Intentional co-doping with Sc + ions was tested and resulted in increase of the Ce distribution coefficient to about 0.3. This enabled to increase the concentration of Ce in LuAP:Ce,Sc crystals up to 0.7 at. %, while conserving high optical quality. In contrast to LuAP:Ce, the light yield in LuAP:Ce,Sc crystals does not increase with Ce concentration, the photo peak being gradually suppressed. The involved mechanisms are discussed basing on measurements of the unit cell volumes, Ce concentration uniformity, x-ray rocking spectra, absorption spectra of pure and variously doped LuAP crystals, and emission spectra under different excitations.

N Termini of apPDE4 Isoforms Are Responsible for Targeting the Isoforms to Different Cellular Membranes

Science.gov (United States)

Jang, Deok-Jin; Park, Soo-Won; Lee, Jin-A; Lee, Changhoon; Chae, Yeon-Su; Park, Hyungju; Kim, Min-Jeong; Choi, Sun-Lim; Lee, Nuribalhae; Kim, Hyoung; Kaang, Bong-Kiun

2010-01-01

Phosphodiesterases (PDEs) are known to play a key role in the compartmentalization of cAMP signaling; however, the molecular mechanisms underlying intracellular localization of different PDE isoforms are not understood. In this study, we have found that each of the supershort, short, and long forms of apPDE4 showed distinct localization in the…

Inhibition of Na+ channel currents in rat myoblasts by 4-aminopyridine

International Nuclear Information System (INIS)

Lu Boxun; Liu Linyun; Liao Lei; Zhang Zhihong; Mei Yanai

2005-01-01

Our previous study revealed that 4-aminopyridine (4-AP), a specific blocker of A-type current, could also inhibit inward Na + currents (I Na ) with a state-independent mechanism in rat cerebellar granule cells. In the present study, we report an inhibitory effect of 4-AP on voltage-gated and tetrodotoxin (TTX)-sensitive I Na recorded from cultured rat myoblasts. 4-AP inhibited I Na amplitude in a dose-dependent manner between the concentrations of 0.5 and 10 mM without significant alteration in the activation or inactivation kinetics of the channel. By comparison to the 4-AP-induced inhibitory effect on cerebellum neurons, the inhibitory effect on myoblasts was enhanced through repetitive pulse and inflected by changing frequency. Specifically, the lower the frequency of pulse, the higher the inhibition observed, suggesting that block manner is inversely use-dependent. Moreover, experiments adding 4-AP to the intracellular solution indicate that the inhibitory effects are localized inside the cell. Additionally, 4-AP significantly modifies the properties of steady-state activation and inactivation kinetics of the channel. Our data suggest that the K + channel blocker 4-AP inhibits both neuron and myoblast Na + channels via different mechanisms. These findings may also provide information regarding 4-AP-induced pharmacological and toxicological effects in clinical use and experimental research

Molecular Basis for Enhancement of the Meiotic DMCI Recombinase by RAD51AP1

Energy Technology Data Exchange (ETDEWEB)

Dray, Eloise; Dunlop, Myun Hwa; Kauppi, Liisa; San Filippo, Joseph San; Wiese, Claudia; Tsai, Miaw-Sheue; Begovic, Sead; Schild, David; Jasin, Maria; Keeney, Scott; Sung, Patrick

2010-11-05

Homologous recombination is needed for meiotic chromosome segregation, genome maintenance, and tumor suppression. RAD51AP1 (RAD51 Associated Protein 1) has been shown to interact with and enhance the recombinase activity of RAD51. Accordingly, genetic ablation of RAD51AP1 leads to enhanced sensitivity to and also chromosome aberrations upon DNA damage, demonstrating a role for RAD51AP1 in mitotic homologous recombination. Here we show physical association of RAD51AP1 with the meiosis-specific recombinase DMC1 and a stimulatory effect of RAD51AP1 on the DMC1-mediated D-loop reaction. Mechanistic studies have revealed that RAD51AP1 enhances the ability of the DMC1 presynaptic filament to capture the duplex DNA partner and to assemble the synaptic complex, in which the recombining DNA strands are homologously aligned. We also provide evidence that functional co-operation is dependent on complex formation between DMC1 and RAD51AP1, and that distinct epitopes in RAD51AP1 mediate interactions with RAD51 and DMC1. Finally, we show that RAD51AP1 is expressed in mouse testes, and that RAD51AP1 foci co-localize with a subset of DMC1 foci in spermatocytes. These results suggest that RAD51AP1 also serves an important role in meiotic homologous recombination.

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

Science.gov (United States)

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. Copyright 2010 Elsevier Inc. All rights reserved.

Got AP?

Science.gov (United States)

Digby, Joan

2016-01-01

Families, especially those considering sending their children to a private four-year university, need all the help they can get in funding college. Annmarie Guzy's essay "AP, Dual Enrollment, and the Survival of Honors Education" in this issue powerfully spells out the financial benefits that accrue from using AP courses to satisfy…

Kcne4 Deletion Sex-Dependently Alters Vascular Reactivity

DEFF Research Database (Denmark)

Abbott, Geoffrey W; Jepps, Thomas A

2016-01-01

transcripts, with no striking sex-specific differences. However, Kv7.4 protein expression in females was twice that in males, and was reduced in both sexes by Kcne4 deletion. Our findings confirm a crucial role for KCNE4 in regulation of Kv7 channel activity to modulate vascular tone, and provide the first......Voltage-gated potassium (Kv) channels formed by Kv7 (KCNQ) α-subunits are recognized as crucial for vascular smooth muscle function, in addition to their established roles in the heart (Kv7.1) and the brain (Kv7.2-5). In vivo, Kv7 α-subunits are often regulated by KCNE subfamily ancillary (β...... known molecular mechanism for sex-specificity of this modulation that has important implications for vascular reactivity and may underlie sex-specific susceptibility to cardiovascular diseases....

A truncated Kv1.1 protein in the brain of the megencephaly mouse: expression and interaction

Directory of Open Access Journals (Sweden)

Århem Peter

2005-11-01

Full Text Available Abstract Background The megencephaly mouse, mceph/mceph, is epileptic and displays a dramatically increased brain volume and neuronal count. The responsible mutation was recently revealed to be an eleven base pair deletion, leading to a frame shift, in the gene encoding the potassium channel Kv1.1. The predicted MCEPH protein is truncated at amino acid 230 out of 495. Truncated proteins are usually not expressed since nonsense mRNAs are most often degraded. However, high Kv1.1 mRNA levels in mceph/mceph brain indicated that it escaped this control mechanism. Therefore, we hypothesized that the truncated Kv1.1 would be expressed and dysregulate other Kv1 subunits in the mceph/mceph mice. Results We found that the MCEPH protein is expressed in the brain of mceph/mceph mice. MCEPH was found to lack mature (Golgi glycosylation, but to be core glycosylated and trapped in the endoplasmic reticulum (ER. Interactions between MCEPH and other Kv1 subunits were studied in cell culture, Xenopus oocytes and the brain. MCEPH can form tetramers with Kv1.1 in cell culture and has a dominant negative effect on Kv1.2 and Kv1.3 currents in oocytes. However, it does not retain Kv1.2 in the ER of neurons. Conclusion The megencephaly mice express a truncated Kv1.1 in the brain, and constitute a unique tool to study Kv1.1 trafficking relevant for understanding epilepsy, ataxia and pathologic brain overgrowth.

Micro-finite-element method to assess elastic properties of trabecular bone at micro- and macroscopic level.

Science.gov (United States)

Rieger, R; Auregan, J C; Hoc, T

2018-03-01

The objective of the present study is to assess the mechanical behavior of trabecular bone based on microCT imaging and micro-finite-element analysis. In this way two methods are detailed: (i) direct determination of macroscopic elastic property of trabecular bone; (ii) inverse approach to assess mechanical properties of trabecular bone tissue. Thirty-five females and seven males (forty-two subjects) mean aged (±SD) 80±11.7 years from hospitals of Assistance publique-Hôpitaux de Paris (AP-HP) diagnosed with osteoporosis following a femoral neck fracture due to a fall from standing were included in this study. Fractured heads were collected during hip replacement surgery. Standardized bone cores were removed from the femoral head's equator by a trephine in a water bath. MicroCT images acquisition and analysis were performed with CTan ® software and bone volume fraction was then determined. Micro-finite-element simulations were per-formed using Abaqus 6.9-2 ® software in order to determine the macroscopic mechanical behaviour of the trabecular bone. After microCT acquisition, a longitudinal compression test was performed and the experimental macroscopic Young's Modulus was extracted. An inverse approach based on the whole trabecular bone's mechanical response and micro-finite-element analysis was performed to determine microscopic mechanical properties of trabecular bone. In the present study, elasticity of the tissue was shown to be similar to that of healthy tissue but with a lower yield stress. Classical histomorphometric analysis form microCT imaging associated with an inverse micro-finite-element method allowed to assess microscopic mechanical trabecular bone parameters. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Westinghouse AP1000 licensing maturity

International Nuclear Information System (INIS)

Schulz, T.; Vijuk, R.P.

2005-01-01

The Westinghouse AP1000 Program is aimed at making available a nuclear power plant that is economical in the U.S deregulated electrical power industry in the near-term. The AP1000 is two-loop 1000 MWe pressurizer water reactor (PWR). It is an up rated version of the AP600. The AP1000 uses passive safety systems to provide significant and measurable improvements in plant simplification, safety, reliability, investment protection and plant costs. The AP1000 uses proven technology, which builds on over 35 years of operating PWR experience. The AP1000 received Final Design Approval by the United States Nuclear Regulatory Commission (U.S. NRC) in September 2004. The AP1000 meets the US utility requirements. The AP1000 and its sister plant the AP600 have gone through a very through and complete licensing review. This paper describes the U.S. NRC review efforts of both the AP600 and the AP1000. The detail of the review and the independent calculations, evaluations and testing is discussed. The AP600 licensing documentation was submitted in 1992. The U.S. NRC granted Final Design Approval in 1999. During the intervening 7 years, the U.S. NRC asked thousands of questions, performed independent safety analysis, audited Westinghouse calculations and analysis, and performed independent testing. The more significant areas of discussion will be described. For the AP1000 Westinghouse first engaged the U.S. NRC in pre-certification discussions to define the extent of the review required, since the design is so similar to the AP600. The AP1000 licensing documentation was submitted in March 2002. The U.S. NRC granted Final Design Approval in September 2004. During the intervening 2 1/2 years, the U.S. NRC asked hundreds of questions, performed independent safety analysis, audited Westinghouse calculations and analysis, and performed independent testing. The more significant areas of discussion will be described. The implications of this review and approval on AP1000 applications in

APS Science 2009.

Energy Technology Data Exchange (ETDEWEB)

Gibson, J. M; Mills, D. M.; Gerig, R.

2010-05-01

It is my pleasure to introduce the 2009 annual report of the Advanced Photon Source. This was a very good year for us. We operated with high reliability and availability, despite growing problems with obsolete systems, and our users produced a record output of publications. The number of user experiments increased by 14% from 2008 to more than 3600. We congratulate the recipients of the 2009 Nobel Prize in Chemistry-Venkatraman Ramakrishnan (Cambridge Institute for Medical Research), Thomas Steitz (Yale University), and Ada Yonath (Weizmann Institute) - who did a substantial amount of this work at APS beamlines. Thanks to the efforts of our users and staff, and the ongoing counsel of the APS Scientific Advisory Committee, we made major progress in advancing our planning for the upgrade of the APS (APS-U), producing a proposal that was positively reviewed. We hope to get formal approval in 2010 to begin the upgrade. With advocacy from our users and the support of our sponsor, the Office of Basic Energy Sciences in the Department of Energy (DOE) Office of Science, our operating budgets have grown to the level needed to more adequately staff our beamlines. We were also extremely fortunate to have received $7.9 M in American Recovery and Reinvestment Act ('stimulus') funding to acquire new detectors and improve several of our beamlines. The success of the new Linac Coherent Light Source at Stanford, the world's first x-ray free-electron laser, made us particularly proud since the undulators were designed and built by the APS. Among other highlights, we note that more than one-quarter of the 46 Energy Frontier Research Centers, funded competitively across the U.S. in 2009 by the DOE, included the Advanced Photon Source in their proposed work, which shows that synchrotron radiation, and the APS in particular, are central to energy research. While APS research covers everything from fundamental to applied science (reflected by the highlights in this report

The American Heart Association Scientific Statement on salt sensitivity of blood pressure: Prompting consideration of alternative conceptual frameworks for the pathogenesis of salt sensitivity?

Czech Academy of Sciences Publication Activity Database

Kurtz, T. W.; DiCarlo, S. E.; Pravenec, Michal; Morris Jr., R. C.

2017-01-01

Roč. 35, č. 11 (2017), s. 2214-2225 ISSN 0263-6352 Grant - others:AV ČR(CZ) AP1502 Program:Akademická prémie - Praemium Academiae Institutional support: RVO:67985823 Keywords : blood pressure * hypertension * salt * salt resistence * salt sensitivity * sodium * sodium sensitivity Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery OBOR OECD: Cardiac and Cardiovascular systems Impact factor: 4.085, year: 2016

Learning through delivery, Westinghouse AP1000 plant construction

International Nuclear Information System (INIS)

Gorgemans, J.; Hinman, R.D.; Steuck, C.M.; Greco, P.L.

2014-01-01

The AP1000 plant, which is a 1100 MWe class pressurized water reactor with passive safety features, is designed around a conventional 2 loop, 2 steam generator primary system configuration with 2 hot legs, 4 reactor coolant pumps directly mounted in the steam generator lower head and 4 cold legs. A particular feature of AP1000 is its modular construction to minimize the time and cost of construction. Modular construction allows activities to be run in parallel, it allows more activities to be performed in a controlled factory instead of in the field, and it provides a better level of quality. The AP1000 plant design includes 106 structural modules and 52 mechanical modules. Structural modules include all penetrations for piping, cable trays, HVAC duct runs, and all reinforcement for pipe, equipment hangers, and supports. Structural modules are shipped in sub-modules to support transportation by rail or truck or barge. Mechanical modules contain equipment such as pumps, tanks, heat exchangers, air-handling units, and filters along with interconnecting pipes, valves, instruments, wiring and support services. Modular construction requires strong coordination between engineering, supply chain and construction. A total of 8 AP1000 units are currently under construction in China and in the United States. The lessons learned and best practices of each new AP1000 construction are systematically incorporated into the standard design. (A.C.)

Vascular Manifestations in Antiphospholipid Syndrome (APS): Is APS a Thrombophilia or a Vasculopathy?

Science.gov (United States)

Siddique, Salma; Risse, Jessie; Canaud, Guillaume; Zuily, Stéphane

2017-09-04

Antiphospholipid antibody syndrome (APS) is characterized primarily by thrombosis and pregnancy morbidity. Chronic vascular lesions can also occur. While the underlying mechanisms of these vascular lesions are not entirely known, there have been multiple theories describing the potential process of vasculopathy in APS and the various clinical manifestations associated with it. Recently, it has been demonstrated that endothelial proliferation in kidneys can be explained by the activation of the mammalian target of rapamycin complex (mTORC) pathway by antiphospholipid antibodies (aPL). These data support the existence of an APS-related vasculopathy in different locations which can explain-in part-the different manifestations of APS. This review focuses on the various manifestations of APS as a result of APS-related vasculopathy, as well as pathophysiology, current screening, and treatment options for clinicians to be aware of.

Kepler observations of rapidly oscillating Ap, δ Scuti and γ Doradus pulsations in Ap stars

DEFF Research Database (Denmark)

Balona, Luis A.; Cunha, Margarida S.; Kurtz, Donald W.

2011-01-01

Observations of the A5p star KIC 8677585 obtained during the Kepler 10-d commissioning run with 1-min time resolution show that it is a rapidly oscillating Ap (roAp) star with several frequencies with periods near 10 min. In addition, a low frequency at 3.142 d−1 is also clearly present....... Multiperiodic γ Doradus (γ Dor) and δ Scuti (δ Sct) pulsations, never before seen in any Ap star, are present in Kepler observations of at least three other Ap stars. Since γ Dor pulsations are seen in Ap stars, it is likely that the low frequency in KIC 8677585 is also a γ Dor pulsation. The simultaneous...... presence of both γ Dor and roAp pulsations and the unexpected detection of δ Sct and γ Dor pulsations in Ap stars present new opportunities and challenges for the interpretation of these stars. Since it is easy to confuse Am and Ap stars at classification dispersions, the nature of these Ap stars...

APS SCIENCE 2016

Energy Technology Data Exchange (ETDEWEB)

Fenner, Richard B. [Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

2017-05-01

The Advanced Photon Source (APS) occupies an 80-acre site on the Argonne national laboratory campus, about 25 miles from downtown chicago, illinois. it shares the site with the center for nanoscale materials and the Advanced Protein characterization facility. for directions to Argonne, see http://www.anl.gov/directions-and-visitor-information. The APS, a national synchrotron radiation research facility operated by Argonne for the u.S. department of energy (doe) office of Science, provides this nation’s brightest high-energy x-ray beams for science. research by APS users extends from the center of the earth to outer space, from new information on combustion engines and microcircuits to new drugs and nanotechnologies whose scale is measured in billionths of a meter. The APS helps researchers illuminate answers to the challenges of our high-tech world, from developing new forms of energy, to sustaining our nation’s technological and economic competitiveness, to pushing back against the ravages of disease. research at the APS promises to have far-reaching

The ladder-shaped polyether toxin gambierol anchors the gating machinery of Kv3.1 channels in the resting state

Science.gov (United States)

Kopljar, Ivan; Labro, Alain J.; de Block, Tessa; Rainier, Jon D.; Tytgat, Jan

2013-01-01

Voltage-gated potassium (Kv) and sodium (Nav) channels are key determinants of cellular excitability and serve as targets of neurotoxins. Most marine ciguatoxins potentiate Nav channels and cause ciguatera seafood poisoning. Several ciguatoxins have also been shown to affect Kv channels, and we showed previously that the ladder-shaped polyether toxin gambierol is a potent Kv channel inhibitor. Most likely, gambierol acts via a lipid-exposed binding site, located outside the K+ permeation pathway. However, the mechanism by which gambierol inhibits Kv channels remained unknown. Using gating and ionic current analysis to investigate how gambierol affected S6 gate opening and voltage-sensing domain (VSD) movements, we show that the resting (closed) channel conformation forms the high-affinity state for gambierol. The voltage dependence of activation was shifted by >120 mV in the depolarizing direction, precluding channel opening in the physiological voltage range. The (early) transitions between the resting and the open state were monitored with gating currents, and provided evidence that strong depolarizations allowed VSD movement up to the activated-not-open state. However, for transition to the fully open (ion-conducting) state, the toxin first needed to dissociate. These dissociation kinetics were markedly accelerated in the activated-not-open state, presumably because this state displayed a much lower affinity for gambierol. A tetrameric concatemer with only one high-affinity binding site still displayed high toxin sensitivity, suggesting that interaction with a single binding site prevented the concerted step required for channel opening. We propose a mechanism whereby gambierol anchors the channel’s gating machinery in the resting state, requiring more work from the VSD to open the channel. This mechanism is quite different from the action of classical gating modifier peptides (e.g., hanatoxin). Therefore, polyether toxins open new opportunities in structure�

AP Music Theory Applied

Science.gov (United States)

Spieker, Matthew H.

2016-01-01

Some American high schools include Advanced Placement (AP) Music Theory within their course offerings. Students who pass the AP exam can receive college credit either as a music or humanities credit. An AP class, however, offers music students more than future college credit; it ultimately improves musicianship skills and promotes deeper…

Marys Lake 69/115-kV transmission line upgrade and substation expansion projects

Energy Technology Data Exchange (ETDEWEB)

NONE

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.

Marys Lake 69/115-kV transmission line upgrade and substation expansion projects

International Nuclear Information System (INIS)

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

400 kV injector compact ECR ion source

International Nuclear Information System (INIS)

Constantin, F.; Catana, D.; Macovei, M.; Ivanov, E.

1997-01-01

Obtaining multiple ionised ions is a fundamental problem for some applications and research. Multiple ionised ions can be produced from electronic bombardment, when n·τ≥5·10 9 cm -3 · s, where n is the density of electrons (in cm -3 ) and τ is the time of interaction between electrons and ions . The relative speed of electrons and ions determines the equilibrium between the stripping process of the atom's electrons and their capture. An ion source with high ionisation efficiency and large output current is the ECR source (Electron Cyclotron Resonance). Using an ECR source with permanent magnets as ion source for the injector will lead to following advantages: - the possibility to obtain multiple ionised particles; - an increase of ion beam intensities; - the expanding of accelerator activities; - a longer working time, due to magnetron lifetime. The ECR ion source is robust, compact and capable of high intensities of extracted ion current. The large functional domain for the residual gas pressure allows the production of multiple charged ions. The source can be easily integrated in the TRILAC's injection structure. We realised a compact microwave ion source which has an axial magnetic field generated by a permanent magnet of Co-Sm. 1200 G magnetic field is greater than the 875 G magnetic field corresponding to the electron-cyclotron frequency of 2.45 GHz. The microwave generator is a magnetron (2.45 GHz and 200 W in continuos wave). The microwave is fed through a coaxial connector on the top of flange. The test was made on He gas at a pressure between 8· 10 -4 and 5·10 -2 torr. The ion beam current was measured vs. extracted potential from 3 kV to 10 kV and has a dependence according to U 3/2 law. A maximal ion current of 300 μA at 10 kV extraction potential was measured. Dimension of ECR ion source, including Einzel lens are φ=12 cm and h=16 cm. (authors)

Roles of AP-2 in clathrin-mediated endocytosis.

Directory of Open Access Journals (Sweden)

Emmanuel Boucrot

2010-05-01

Full Text Available The notion that AP-2 clathrin adaptor is an essential component of an endocytic clathrin coat appears to conflict with recent observations that substantial AP-2 depletion, using RNA interference with synthesis of AP-2 subunits, fails to block uptake of certain ligands known to internalize through a clathrin-based pathway.We report here the use of in vivo imaging data obtained by spinning-disk confocal microscopy to study the formation of clathrin-coated structures at the plasma membranes of BSC1 and HeLa cells depleted by RNAi of the clathrin adaptor, AP-2. Very few clathrin coats continue to assemble after AP-2 knockdown. Moreover, there is a total absence of clathrin-containing structures completely lacking AP-2 while all the remaining coats still contain a small amount of AP-2. These observations suggest that AP-2 is essential for endocytic coated-pit and coated-vesicle formation. We also find that AP-2 knockdown strongly inhibits light-density lipoprotein (LDL receptor-mediated endocytosis, as long as cells are maintained in complete serum and at 37 degrees C. If cells are first incubated with LDL at 4 degrees C, followed by warming, there is little or no decrease in LDL uptake with respect to control cells. LDL uptake at 37 degrees C is also not affected in AP-2 depleted cells first deprived of LDL by incubation with either serum-starved or LDL-starved cells for 24 hr. The LDL-deprived cells display a significant increase in endocytic structures enriched on deeply invaginated tubes that contain LDL and we suggest that under this condition of stress, LDL might enter through this alternative pathway.These results suggest that AP-2 is essential for endocytic clathrin coated-pit and coated-vesicle formation. They also indicate that under normal conditions, functional endocytic clathrin coated pits are required for LDL internalization. We also show that under certain conditions of stress, cells can upregulate alternative endocytic structures

Intratumoral Macroscopic Fat and Hemorrhage Combination Useful in the Differentiation of Benign and Malignant Solid Renal Masses.

Science.gov (United States)

Sun, Jun; Xing, Zhaoyu; Xing, Wei; Zheng, Linfeng; Chen, Jie; Fan, Min; Chen, Tongbing; Zhang, Zhuoli

2016-03-01

To evaluate the value of combining the detection of intratumoral macroscopic fat and hemorrhage in the differentiation of the benign from malignant solid renal masses.Conventional magnetic resonance imaging (MRI), chemical shift (CS)-MRI, and susceptibility-weighted imaging were performed in 152 patients with 152 solid renal masses, including 48 benign and 104 malignant masses all pathologically confirmed. The presence of macroscopic fat detected by CS-MRI and hemorrhage detected by susceptibility-weighted imaging were evaluated in all masses. The rates of macroscopic fat and hemorrhage observed between benign and malignant masses were compared by a χ test. All masses found to contain macroscopic fat with or without hemorrhage were considered to be benign. The remaining masses (without macroscopic fat) found not to contain hemorrhage were considered to be benign. Only those found to contain hemorrhage alone were considered to be malignant. The evaluation indexes for differentiating and forecasting the benign and malignant masses were calculated.Significant differences in the rate of macroscopic fat (observed in 85.42% of benign masses vs. 0% of malignant masses) and hemorrhage (observed in 4.17% of benign masses vs. 95.19% of malignant masses) were measured in the benign and malignant groups (P benign and malignant masses were 96.05%, 95.19%, and 97.92%, respectively, and the accuracy and error rate of forecasting the benign and malignant masses were 95.39% and 4.61%, respectively.Combining the detection intratumoral macroscopic fat and hemorrhage can be used to differentiate the benign from malignant solid renal masses.

A study on the insulation coordination of 765 kV system

Energy Technology Data Exchange (ETDEWEB)

Kim, Jeong Boo; Shim, Eung Bo [Korea Electric Power Corp. (KEPCO), Taejon (Korea, Republic of). Research Center; Lee, Yong Han; Youn, Jae Yeong; Hwang, Chi Woo; Jung, Dong Hak [Korea Electrotechnology Research Inst., Changwon (Korea, Republic of)

1996-12-31

Analysis of the power frequency temporary overvoltage. Analysis of switching surges - Fault imitation, closing and re closing, fault clearing. Analysis of lightning surges. Insulation design of 765 kV overhead transmission line. Insulation coordination of 765 kV gas insulated substation. Transient recovery voltage and high speed ground switch (author). 38 refs., 55 figs.

Case of small hepatocellular carcinoma detected only by dynamic sequential computed tomography with table incrementation during arterial portography (DSCTI-AP)

Energy Technology Data Exchange (ETDEWEB)

Nishijima, Hiroshi; Ida, Masahiro; Takayama, Shigeru; Yanaghi, Sekiya; Kuroda, Yuzuru [Fukui Saiseikai Hospital (Japan)

1984-05-01

A 62 years old woman was admitted for liver cirrhosis with esophageal varix. Radionuclide liver scintigram, ultrasonogram, computed tomography and infusion hepatic angiography showed no signs of hepatocellular carcinoma (HCC). But DSCTI-AP detected a small solid mass lesion about 1.5cm in diameter in the right lobe of the liver. It was difficult to diagnose this lesion as HCC because of low titer of serum ..cap alpha../sub 1/-fetoprotein. After the esophageal transection for esophageal varices, she was followed as an outpatient. Six months later, serum ..cap alpha../sub 1/-fetoprotein was slightly elevated (130 ng/ml), and all imaging methods were carried out for the detection of HCC. Ultrasonogram, computed tomography, infusion hepatic angiography, DSCTI-AP all showed hepatocellular carcinoma, about 4.5cm in diameter in the same site where a small nodule was visualized by DSCTI-AP performed 5 months ago. This case suggests that DSCTI-AP is a sensitive and useful method for detection of some type of small liver cancer.

A new gap separation mechanism for APS insertion devices

International Nuclear Information System (INIS)

Trakhtenberg, E. M.; Tcheskidov, V.; Den Hartog, P. K.; Deriy, B.; Erdmann, M.; Makarov, O.; Moog, E. R.

1999-01-01

A new gap separation mechanism for use with the standard Advanced Photon Source (APS) 3.3-cm-period undulator magnetic structures has been designed and built and the first system has been installed in the APS storage ring. The system allows a minimum magnetic gap of 10 mm for use with the APS 8-mm insertion device vacuum chambers. The mechanism is a bolted steel frame structure with a simple 4-motor mechanical drive train. The control system uses servomotors with incremental rotary encoders and virtual absolute linear encoders

Pharmacological Targeting Of Neuronal Kv7.2/3 Channels: A Focus On Chemotypes And Receptor Sites.

Science.gov (United States)

Miceli, Francesco; Soldovieri, Maria Virginia; Ambrosino, Paolo; Manocchio, Laura; Medoro, Alessandro; Mosca, Ilaria; Taglialatela, Maurizio

2017-10-12

The Kv7 (KCNQ) subfamily of voltage-gated potassium channels consists of 5 members (Kv7.1-5) each showing a characteristic tissue distribution and physiological roles. Given their functional heterogeneity, Kv7 channels represent important pharmacological targets for development of new drugs for neuronal, cardiac and metabolic diseases. In the present manuscript, we focus on describing the pharmacological relevance and the potential therapeutic applications of drugs acting on neuronally-expressed Kv7.2/3 channels, placing particular emphasis on the different modulator chemotypes, and highlighting their pharmacodynamic and, whenever possible, pharmacokinetic peculiarities. The present work is based on an in-depth search of the currently available scientific literature, and on our own experience and knowledge in the field of neuronal Kv7 channel pharmacology. Space limitations impeded to describe the full pharmacological potential of Kv7 channels; thus, we have chosen to focus on neuronal channels composed of Kv7.2 and Kv7.3 subunits, and to mainly concentrate on their involvement in epilepsy. An astonishing heterogeneity in the molecular scaffolds exploitable to develop Kv7.2/3 modulators is evident, with important structural/functional peculiarities of distinct compound classes. In the present work we have attempted to show the current status and growing potential of the Kv7 pharmacology field. We anticipate a bright future for the field, and we express our hopes that the efforts herein reviewed will result in an improved treatment of hyperexcitability (or any other) diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Optimizing monoscopic kV fluoro acquisition for prostate intrafraction motion evaluation

International Nuclear Information System (INIS)

Adamson, Justus; Wu Qiuwen

2009-01-01

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 the 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, and 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 and 5.5 mGy, depending on the 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.

A Brightness-Referenced Star Identification Algorithm for APS Star Trackers

Science.gov (United States)

Zhang, Peng; Zhao, Qile; Liu, Jingnan; Liu, Ning

2014-01-01

Star trackers are currently the most accurate spacecraft attitude sensors. As a result, they are widely used in remote sensing satellites. Since traditional charge-coupled device (CCD)-based star trackers have a limited sensitivity range and dynamic range, the matching process for a star tracker is typically not very sensitive to star brightness. For active pixel sensor (APS) star trackers, the intensity of an imaged star is valuable information that can be used in star identification process. In this paper an improved brightness referenced star identification algorithm is presented. This algorithm utilizes the k-vector search theory and adds imaged stars' intensities to narrow the search scope and therefore increase the efficiency of the matching process. Based on different imaging conditions (slew, bright bodies, etc.) the developed matching algorithm operates in one of two identification modes: a three-star mode, and a four-star mode. If the reference bright stars (the stars brighter than three magnitude) show up, the algorithm runs the three-star mode and efficiency is further improved. The proposed method was compared with other two distinctive methods the pyramid and geometric voting methods. All three methods were tested with simulation data and actual in orbit data from the APS star tracker of ZY-3. Using a catalog composed of 1500 stars, the results show that without false stars the efficiency of this new method is 4∼5 times that of the pyramid method and 35∼37 times that of the geometric method. PMID:25299950

Compact 250-kV injector system for PIGMI

International Nuclear Information System (INIS)

Hamm, R.W.; Stevens, R.R. Jr.; Mueller, D.W.; Lederer, H.M.

1978-01-01

A 250-kV proton injector to be used in the development of a linac suitable for medical applications has been constructed. This injector utilizes a spherical Pierce geometry to produce a converging beam. A gas insulated accelerating column is cantilevered on a grounded vacuum system, with a separate high voltage equipment dome connected to a 300-kV Cockcroft-Walton power supply. The injector can be operated locally or remotely, with the remote control accomplished by a microprocessor system linked to a central control minicomputer. This injector has been designed as a low-cost compact system. The design details and the data obtained during initial operation are presented

Usefulness of combining gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging and contrast-enhanced ultrasound for diagnosing the macroscopic classification of small hepatocellular carcinoma.

Science.gov (United States)

Kobayashi, Tomoki; Aikata, Hiroshi; Hatooka, Masahiro; Morio, Kei; Morio, Reona; Kan, Hiromi; Fujino, Hatsue; Fukuhara, Takayuki; Masaki, Keiichi; Ohno, Atsushi; Naeshiro, Noriaki; Nakahara, Takashi; Honda, Yohji; Murakami, Eisuke; Kawaoka, Tomokazu; Tsuge, Masataka; Hiramatsu, Akira; Imamura, Michio; Kawakami, Yoshiiku; Hyogo, Hideyuki; Takahashi, Shoichi; Chayama, Kazuaki

2015-11-01

Non-simple nodules in hepatocellular carcinoma (HCC) correlate with poor prognosis. Therefore, we examined the diagnostic ability of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) and contrast-enhanced ultrasound (CEUS) for diagnosing the macroscopic classification of small HCCs. A total of 85 surgically resected nodules (≤30 mm) were analyzed. HCCs were pathologically classified as simple nodular (SN) and non-SN. By evaluating hepatobiliary phase (HBP) of EOB-MRI and Kupffer phase of CEUS, the diagnostic abilities of both modalities to correctly distinguish between SN and non-SN were compared. Forty-six nodules were diagnosed as SN and the remaining 39 nodules as non-SN. The area under the ROC curve (AUROCs, 95% confidence interval) for the diagnosis of non-SN were EOB-MRI, 0.786 (0.682-0.890): CEUS, 0.784 (0.679-0.889), in combination, 0.876 (0.792-0.959). The sensitivity, specificity, and accuracy were 64.1%, 95.7%, and 81.2% in EOB-MRI, 56.4%, 97.8%, and 78.8% in CEUS, and 84.6%, 95.7%, and 90.6% in combination, respectively. High diagnostic ability was obtained when diagnosed in both modalities combined. The sensitivity was especially statistically significant compared to CEUS. Combined diagnosis by EOB-MRI and CEUS can provide high-quality imaging assessment for determining non-SN in small HCCs. • Non-SN has a higher frequency of MVI and intrahepatic metastasis than SN. • Macroscopic classification is useful to choose the treatment strategy for small HCCs. • Diagnostic ability for macroscopic findings of EOB-MRI and CEUS were statistically equal. • The diagnosis of macroscopic findings by individual modality has limitations. • Combined diagnosis of EOB-MRI and CEUS provides high diagnostic ability.

Macroscopic Optomechanically Induced Transparency

Science.gov (United States)

Pate, Jacob; Castelli, Alessandro; Martinez, Luis; Thompson, Johnathon; Chiao, Ray; Sharping, Jay

Optomechanically induced transparency (OMIT) is an effect wherein the spectrum of a cavity resonance is modified through interference between coupled excitation pathways. In this work we investigate a macroscopic, 3D microwave, superconducting radio frequency (SRF) cavity incorporating a niobium-coated, silicon-nitride membrane as the flexible boundary. The boundary supports acoustic vibrational resonances, which lead to coupling with the microwave resonances of the SRF cavity. The theoretical development and physical understanding of OMIT for our macroscopic SRF cavity is the same as that for other recently-reported OMIT systems despite vastly different optomechanical coupling factors and device sizes. Our mechanical oscillator has a coupling factor of g0 = 2 π . 1 ×10-5 Hz and is roughly 38 mm in diameter. The Q = 5 ×107 for the SRF cavity allows probing of optomechanical effects in the resolved sideband regime.

Macroscopic averages in Qed in material media

International Nuclear Information System (INIS)

Dutra, S.M.; Furuya, K.

1997-01-01

The starting point of macroscopic theories of quantum electrodynamics in material media is usually the classical macroscopic Maxwell equations that are then quantized. Such approach however, is based on the assumption that a macroscopic description is attainable, i.e., it assumes that we can describe the effect of the atoms of material on the field only in terms of a dielectric constant in the regime where the field has to be treated quantum mechanically. The problem we address is whether this assumption is valid at all and if so, under what conditions. We have chosen a simple model, which allows us to start from first principles and determine the validity of these approximations, without simply taking them for granted as in previous papers

735 kV air-blast circuit breakers for Hydro Quebec

Energy Technology Data Exchange (ETDEWEB)

Lindstrom, I

1966-01-01

In 1962 the Quebec Hydro-Electric Commission started the development of aproject for utilizing water power in Manicouagan and Outardes, two rivers some 350 miles northeast of the city of Montreal on the left bank of the St. Lawrence estuary. The project involved the transmission of power at 735 kV ac from Manicouagan and Outardes to the heavy and growing load centers of Quebec and Montreal. The total amount of energy to be transmitted in the final stage is about 6,000 MW. The project involved the need of considerable quantities of apparatus for 735 kV, such as transformers, reactors, lightning arrestors, circuit-breakers, and disconnectors. Since the supply of the major part of the 735 kV circuit-breakers, altogether 14 three-pole units, was awarded to ASEA in Sweden, a short presentation of these airblast circuit-breakers is presented.

AP1000 Design for Security

International Nuclear Information System (INIS)

Long, L.B.; Cummins, W.E.; Winters, J.W.

2006-01-01

Nuclear power plants are protected from potential security threats through a combination of robust structures around the primary system and other vital equipment, security systems and equipment, and defensive strategy. The overall objective for nuclear power plant security is to protect public health and safety by ensuring that attacks or sabotage do not challenge the ability to safely shutdown the plant or protect from radiological releases. In addition, plants have systems, features and operational strategies to cope with external conditions, such as loss of offsite power, which could be created as part of an attack. Westinghouse considered potential security threats during design of the AP1000 PWR. The differences in plant configuration, safety system design, and safe shutdown equipment between existing plants and AP1000 affect potential vulnerabilities. This paper provides an evaluation of AP1000 with respect to vulnerabilities to security threats. The AP1000 design differs from the design of operating PWRs in the US in the configuration and the functional requirements for safety systems. These differences are intentional departures from conventional PWR designs which simplify plant design and enhance overall safety. The differences between the AP1000 PWR and conventional PWRs can impact vulnerabilities to security threats. The NRC addressed security concerns as part of their reviews for AP1000 Design Certification, and did not identify any security issues of concern. However, much of the detailed security design information for the AP1000 was deferred to the combined Construction and Operating License (COL) phase as many of the security issues are site-specific. Therefore, NRC review of security issues related to the AP1000 is not necessarily complete. Further, since the AP1000 plant design differs from existing PWRs, it is not obvious that the analyses and assessments prepared for existing plants also apply to the AP1000. We conclude that, overall, the AP1000

CEBAF 200 kV Inverted Electron Gun

International Nuclear Information System (INIS)

Grames, J.M.; Adderley, P.A.; Clark, J.; Hansknecht, J.; Poelker, M.; Stutzman, M.L.; Suleiman, R.; Surles-Law, K.E.L.

2011-01-01

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 and D studies leading toward a production 200keV GaAs photogun for CEBAF will be presented.

Anti-phosphatidylserine/prothrombin antibodies: an additional diagnostic marker for APS?

Science.gov (United States)

Pregnolato, Francesca; Chighizola, Cecilia B; Encabo, Susan; Shums, Zakera; Norman, Gary L; Tripodi, Armando; Chantarangkul, Veena; Bertero, Tiziana; De Micheli, Valeria; Borghi, Maria Orietta; Meroni, Pier Luigi

2013-07-01

Among the diagnostic assays for anti-phospholipid syndrome (APS), lupus anticoagulant (LA) is the strongest predictor of thrombosis; however, it presents several limitations as interference with anticoagulant therapy and poor inter-laboratory agreement. Two-thirds of LA activity is apparently due to antibodies against prothrombin (PT), usually detectable by ELISA. Binding of PT to phosphatidylserine (PS) has been shown to enhance solid-phase anti-PT assay sensitivity. To determine the prevalence of antibodies against PS/PT (aPS/PT) in APS, we tested the semiquantitative QUANTA Lite(®) aPS/PT ELISA in a cohort of 80 APS patients. The prevalence of aPS/PT was 81.3%, rising to 87.6% when considering LA-positive subjects only. We observed a strong correlation between aPS/PT and LA (p = 0.006). To note, APS patients with thrombotic manifestations displayed significantly higher IgG aPS/PT titers compared to 20 aPL asymptomatic carriers (p = 0.012). To rule out a possible cross-reactivity of anti-β2 glycoprotein I antibodies (aβ2GPI) with PS/PT complex, we tested two monoclonal aβ2GPI antibodies and an affinity-purified (AP) polyclonal aβ2GPI IgG obtained from the serum of a patient reacting against both β2GPI and PS/PT. The two monoclonal antibodies did not show any reactivity against PS/PT complex, similarly the AP IgGs did not react toward PS/PT antigen while preserved their aβ2GPI activity. Our findings suggest that aPS/PT are a definite antibody population in APS. Moreover, the good correlation between aPS/PT ELISA and LA may support its use as a surrogate test for LA, particularly useful to overcome the technical limitations of the functional assay.

First 735 kV transmission, Manicouagan, Montreal

Energy Technology Data Exchange (ETDEWEB)

Cahill, L

1964-11-01

The 735 kV transmission network of Hydro Quebec is described giving reasons for choice of voltage, stability factors level of insulation, disposition of conductors, insulators, equipment used and state of readiness of the project.

Major Refit for CERN's 400 kV Substation (Part of the new control and protection system for the 18 kV side)

CERN Document Server

2001-01-01

The 400 kV substation on the Prévessin site brings in the electricity that powers CERN's accelerators and the majority of the Laboratory's installations. It was originally built in the 1970s for the SPS, and is one of only five privately owned 400 kV sub-stations in France. Three of the others belong to the national railway company, SNCF, supplying the Paris-Marseilles TGV line, the other is at the Cadarache research centre near mouth of the Rhone. After nearly thirty years of service, CERN's substation has just undergone a complete overhaul.

The short-circuit test results of 6.9 kV/2.3 kV 400 kVA-class YBCO model transformer with fault current limiting function

International Nuclear Information System (INIS)

Tomioka, A.; Bohno, T.; Kakami, S.; Isozaki, M.; Watanabe, K.; Toyama, K.; Sugiyama, S.; Konno, M.; Gosho, Y.; Okamoto, H.; Hayashi, H.; Tsutsumi, T.; Iwakuma, M.; Saito, T.; Tanabe, K.; Shiohara, Y.

2013-01-01

Highlights: ► We manufactured the 400 kV A-class YBCO model transformer with FCL function. ► Short-circuit test was performed by applying 6.9 kV on primary side. ► The short-circuit current was limited to 174 A for a prospective current of 559 A. ► It agreed with the design and we also confirmed the I c did not degrade. ► The results suggest the possibility to design YBCO transformers with FCL function. -- Abstract: We are developing an elemental technology for 66/6.9 kV 20 MVA-class superconducting power transformer with fault current limiting function. In order to obtain the characteristics of YBCO conductor when the AC over current supplied to the conductor, the model coils were manufactured with YBCO tapes and tested. Based on these results, we manufactured the 6.9 kV/2.3 kV 400 kVA-class YBCO model transformer with fault current limiting function and performed short-circuit test. At the 0.25 s after short-circuit, the short-circuit current of primary winding was limited to about 174 A for a prospective current of 559 A. It was consistent with the design. The I–V characteristics of the winding did not change before and after the test. We consider the model transformer to be able to withstand AC over-current with the function of current limiting. The results suggest the possibility to design YBCO superconducting transformers with fault current limiting function for practical power grid

Specific Kv1.3 blockade modulates key cholesterol-metabolism-associated molecules in human macrophages exposed to ox-LDL.

Science.gov (United States)

Yang, Yong; Wang, Yan-Fu; Yang, Xiao-Fang; Wang, Zhao-Hui; Lian, Yi-Tian; Yang, Ying; Li, Xiao-Wei; Gao, Xiang; Chen, Jian; Shu, Yan-Wen; Cheng, Long-Xian; Liao, Yu-Hua; Liu, Kun

2013-01-01

Cholesterol-metabolism-associated molecules, including scavenger receptor class A (SR-A), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), CD36, ACAT1, ABCA1, ABCG1, and scavenger receptor class B type I, can modulate cholesterol metabolism in the transformation from macrophages to foam cells. Voltage-gated potassium channel Kv1.3 has increasingly been demonstrated to play an important role in the modulation of macrophage function. Here, we investigate the role of Kv1.3 in modulating cholesterol-metabolism-associated molecules in human acute monocytic leukemia cell-derived macrophages (THP-1 macrophages) and human monocyte-derived macrophages exposed to oxidized LDL (ox-LDL). Human Kv1.3 and Kv1.5 channels (hKv1.3 and hKv1.5) are expressed in macrophages and form a heteromultimeric channel. The hKv1.3-E314 antibody that we had generated as a specific hKv1.3 blocker inhibited outward delayed rectifier potassium currents, whereas the hKv1.5-E313 antibody that we had generated as a specific hKv1.5 blocker failed. Accordingly, the hKv1.3-E314 antibody reduced percentage of cholesterol ester and enhanced apoA-I-mediated cholesterol efflux in THP-1 macrophages and human monocyte-derived macrophages exposed to ox-LDL. The hKv1.3-E314 antibody downregulated SR-A, LOX-1, and ACAT1 expression and upregulated ABCA1 expression in THP-1 macrophages and human monocyte-derived macrophages. Our results reveal that specific Kv1.3 blockade represents a novel strategy modulating cholesterol metabolism in macrophages, which benefits the treatment of atherosclerotic lesions.

Modellering og måling af metan-emission fra kvæg

DEFF Research Database (Denmark)

Storm, I; Hellwing, Anne Louise Frydendahl; Nielsen, N I

2011-01-01

Udvikling af og kendskab til de metoder, der bruges til måling af kvægs metan-emission udgør en vigtig del af forskningen indenfor området. I dette indlæg præsenteres de mest anvendte metoder til måling og estimation af kvægs metan-emission, herunder modeller, in vitro inkubation, kammer-metoder,......-metoder, SF6-metoden og CO2-metoden. De enkelte metoder beskrives og fordele, ulemper og anvendelsesområder sammenlignes. Dette er vigtig baggrundsinformation for forståelse og fortolkning af øvrige forskningsresultater og for at kunne planlægge fremtidige projekter.......Udvikling af og kendskab til de metoder, der bruges til måling af kvægs metan-emission udgør en vigtig del af forskningen indenfor området. I dette indlæg præsenteres de mest anvendte metoder til måling og estimation af kvægs metan-emission, herunder modeller, in vitro inkubation, kammer...

Mutation in the kv3.3 voltage-gated potassium channel causing spinocerebellar ataxia 13 disrupts sound-localization mechanisms.

Directory of Open Access Journals (Sweden)

John C Middlebrooks

Full Text Available Normal sound localization requires precise comparisons of sound timing and pressure levels between the two ears. The primary localization cues are interaural time differences, ITD, and interaural level differences, ILD. Voltage-gated potassium channels, including Kv3.3, are highly expressed in the auditory brainstem and are thought to underlie the exquisite temporal precision and rapid spike rates that characterize brainstem binaural pathways. An autosomal dominant mutation in the gene encoding Kv3.3 has been demonstrated in a large Filipino kindred manifesting as spinocerebellar ataxia type 13 (SCA13. This kindred provides a rare opportunity to test in vivo the importance of a specific channel subunit for human hearing. Here, we demonstrate psychophysically that individuals with the mutant allele exhibit profound deficits in both ITD and ILD sensitivity, despite showing no obvious impairment in pure-tone sensitivity with either ear. Surprisingly, several individuals exhibited the auditory deficits even though they were pre-symptomatic for SCA13. We would expect that impairments of binaural processing as great as those observed in this family would result in prominent deficits in localization of sound sources and in loss of the "spatial release from masking" that aids in understanding speech in the presence of competing sounds.

Comparative assessment of 3.3kV/400A SiC MOSFET and Si IGBT power modules

DEFF Research Database (Denmark)

Ionita, Claudiu; Nawaz, Muhammad; Ilves, Kalle

2017-01-01

In this paper, a comparative evaluation between a commercial 3.3 kV/400 A Si-IGBT and a 3.3 kV/400 A SiC MOSFET power module in half-bridge configuration is presented. With a constant current of 250 A, a lower forward voltage (VDS) drop of 1.6 V is obtained for SiC MOSFET at 300 K compared to Si ...... the pulse duration was increased to 4 μs, where a short-circuit energy of 9.1 J was obtained. The cause of the failure is the thermal runaway leading to a drain-source short....

Autoimmune polyglandular syndrome type 3 (APS-3) among patients with premature ovarian insufficiency (POI).

Science.gov (United States)

Szlendak-Sauer, Katarzyna; Jakubik, Daniel; Kunicki, Michał; Skórska, Jolanta; Smolarczyk, Roman

2016-08-01

Autoimmune polyglandular syndrome type 3 - (APS-3), is defined as the coexistence of autoimmune thyroiditis with other non-ovarian autoimmune diseases without primary adrenal insufficiency. Additionally the definition of APS-3 also includes primary ovarian insufficiency (POI) coexistence with autoimmune thyroiditis. The main goal of that study is to assess the prevalence of APS-3 defined as coexistence of autoimmune thyroiditis with POI in population of 46 XX karyotype women with primary ovarian insufficiency (POI). The second goal is to investigate hormonal profile and insulin sensitivity in women with POI and subgroups of women with APS-3 - POI/APS-3(+) and without APS 3 - POI/APS-3(-). Anthropometric measurements, coexistence of autoimmune diseases, androgens, fasting glucose and insulin, glucose and insulin at 60' and 120' of oral glucose tolerance test (OGTT) and homeostasis model for insulin resistance (HOMA-IR), were determine in 98 patients aged between 18 and 39 with spontaneous 46 XX primary ovarian insufficiency (POI), in 33 POI/APS-3(+), 65 POI/APS-3(-), and 75 healthy controls. Continuous data were summarized by the mean±standard deviation (SD), and categorical data by number (percentages). Data were checked for normality using Shapiro-Wilk test, the comparison between groups were performed using non-parametric Mann-Whitney or Kruskall-Wallis test. Pearson's correlation coefficient was used to assess the relationships between parameters. Statistical significance was defined as p values APS-3(+) and POI/APS-3(-) showed significantly lower serum androgens in comparison to controls. Additionally women with POI/APS-3(+) showed hyperinsulinemia after 1h of OGTT; No significant differences in serum fasting glucose, insulin and during 2h OGTT between groups were observed. The prevalence of APS-3 is 33.7% in patients with spontaneous 46 XX primary ovarian insufficiency. Women with POI, POI/APS-3(+) and POI/APS-3(-) feature lower testosterone, androstendione

Vinpocetine inhibits glutamate release induced by the convulsive agent 4-aminopyridine more potently than several antiepileptic drugs.

Science.gov (United States)

Sitges, M; Sanchez-Tafolla, B M; Chiu, L M; Aldana, B I; Guarneros, A

2011-10-01

4-Aminopyridine (4-AP) is a convulsing agent that in vivo preferentially releases Glu, the most important excitatory amino acid neurotransmitter in the brain. Here the ionic dependence of 4-AP-induced Glu release and the effects of several of the most common antiepileptic drugs (AEDs) and of the new potential AED, vinpocetine on 4-AP-induced Glu release were characterized in hippocampus isolated nerve endings pre-loaded with labelled Glu ([3H]Glu). 4-AP-induced [3H]Glu release was composed by a tetrodotoxin (TTX) sensitive and external Ca2+ dependent fraction and a TTX insensitive fraction that was sensitive to the excitatory amino acid transporter inhibitor, TBOA. The AEDs: carbamazepine, phenytoin, lamotrigine and oxcarbazepine at the highest dose tested only reduced [3H]Glu release to 4-AP between 50-60%, and topiramate was ineffective. Vinpocetine at a much lower concentration than the above AEDs, abolished [3H]Glu release to 4-AP. We conclude that the decrease in [3H]Glu release linked to the direct blockade of presynaptic Na+ channels, may importantly contribute to the anticonvulsant actions of all the drugs tested here (except topiramate); and that the significantly greater vinpocetine effect in magnitude and potency on [3H]Glu release when excitability is exacerbated like during seizures, may involve the increase additionally exerted by vinpocetine in some K+ channels permeability. Copyright © 2011 Elsevier B.V. All rights reserved.

Theoretical studies on the electronic and optoelectronic properties of [A.2AP(w)/A*.2AP(WC)/C.2AP(w)/C*.2AP(WC)/C.A(w)/C*.A(WC)]-Au8 mismatch nucleobase complexes

Science.gov (United States)

Srivastava, Ruby

2018-01-01

The electronic and optoelectronic properties of [A.2AP(w)/A*.2AP(WC)/C.2AP(w)/C*.2AP(WC)/C.A(w)/ C*.A(WC)]-Au8 metal-mismatch nucleobase complexes are investigated by means of density functional theory and time-dependent methods. We selected these mispairs as 2-aminopurine (2AP) produces incorporation errors when binding with cytosine (C) into the wobble (w) C.2AP(w) mispair, and is tautomerised into Watson-Crick (WC)-like base mispair C*.2AP(WC) and less effectively produces A.2AP(w)/A*.2AP(WC) mispairs. The vertical ionisation potential, vertical electron affinity, hardness and electrophilicity index of these complexes have also been discussed. The modifications of energy levels and charge density distributions of the frontier orbitals are also analysed. The absorption spectra of these complexes lie in the visible region, which suggests their application in fluorescent-bio imaging. The mechanism of cooperativity effect is studied by molecular orbital potential (MEP), atoms-in-molecules (AIM) and natural bond orbital analyses. Most metalated pairs have smaller HOMO-LUMO band gaps than the isolated mismatch nucleobases which suggest interesting consequences for electron transfer through DNA duplexes.

35-kV GaAs subnanosecond photoconductive switches

Science.gov (United States)

Pocha, Michael D.; Druce, Robert L.

1990-12-01

High-voltage, fast-pulse generation using GaAs photoconductive switches is investigated. It is possible to to generate 35-kV pulses with risetimes as short as 135 ps using 5-mm gap switches, and electric field hold-off of greater than 100 kV/cm is achieved. An approximately 500-ps FWHM on/off electrical pulse is generated with an amplitude of approximately 3 kV using neutron-irradiated GaAs having short carrier lifetimes. Experimental results are described, and fabrication of switches and the diagnostics used to measure these fast signals are discussed. Experience with the nonlinear lock-on and avalanche modes of operation observed in GaAs is also described.

Design and development of a high-power, 500 kV pulsed line

International Nuclear Information System (INIS)

Nicolas, A.

A study was made of very high voltage (500 kV) pulse production for 50 ns at half height. A coaxial line was coupled to a Marx generator for obtaining the pulses on an impedance-adapted electron diode. The maximum power obtained was 6.4 x 10 10 W with a current front in the diode of about 30 ns (80 ns pulse length at half height)

Press-pack components electro-thermo-fluidic modeling: application to the Integrated Gate Commutated Thyristor 4,5 kV-4 kA; Modelisation des couplages electro-thermo-fluidiques des composants en boitier press-pack: application a l'integrated gate commutated thyristor 4,5kV-4kA

Energy Technology Data Exchange (ETDEWEB)

Feral, H.

2005-09-15

Temperature is an important parameter when you use semi-conductors. In the multi MW power converters the semiconductor losses are upper than kW. The thermal analyzes of the semiconductor package and cooling system must be performed to understand the thermal limitations. The maximal temperature can not be upper than 150 deg. C for silicon components. The temperature variations have an impact on the component life time. The thermal phenomena in the power electronic component can not be dissociated with the electric phenomena (losses) and fluidic phenomena (cooling). An electro-thermo-fluidic modelling method has been elaborated. The method is used to study an IGCT (Integrated Gate commutated Thyristor) 4.5 kV 4 kA in the switching cell with his water cooling system. The IGCT use a press-pack floating mount package technology. The thermal contact resistances have an important impact on the heat transfer in the package. The thermal contact resistances have been estimated with a profile-metric measure and a direct measure. To validate the method and tune the model, thermal, electric and fluidic measurements are performed in an IGCT in MW switching operation. The last chapter introduces the model applications. The model is used to study the water flow direction in the IGCT cooling system. Transient simulations are used to study the temperature fluctuation on an arc furnace melting cycle. (author)

Relative Biologic Effectiveness (RBE) of 50 kV X-rays Measured in a Phantom for Intraoperative Tumor-Bed Irradiation

Energy Technology Data Exchange (ETDEWEB)

Liu, Qi; Schneider, Frank; Ma, Lin; Wenz, Frederik [Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim (Germany); Herskind, Carsten, E-mail: carsten.herskind@medma.uni-heidelberg.de [Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim (Germany)

2013-03-15

Purpose: Intraoperative radiation therapy (IORT) with low-energy x-rays is used to treat the tumor bed during breast-conserving surgery. The purpose was to determine the relative biologic effectiveness (RBE) of 50-kV x-rays for inactivation of cells irradiated in a tumor-bed phantom. Methods and Materials: The RBE was determined for clonogenic inactivation of human tumor and normal cells (MCF7, human umbilical vein endothelial cells, normal skin fibroblasts), and hamster V79 cells. The 50-kV x-rays from the Intrabeam machine (Carl Zeiss Surgical) with a spherical 4-cm applicator were used. Cells were irradiated in a water-equivalent phantom at defined distances (8.1-22.9 mm) from the applicator surface. The 50-kV x-rays from a surface therapy machine (Dermopan, Siemens) were included for comparison; 6-MV x-rays were used as reference radiation. Results: At 8.1-mm depth in the phantom (dose rate 15.1 Gy/h), mean RBE values of 50-kV x-rays from Intrabeam were 1.26 to 1.42 for the 4 cell types at doses yielding surviving fractions in the range of 0.01 to 0.5. Confidence intervals were in the range of 1.2 and 1.5. Similar RBE values were found for 50-kV x-rays from Dermopan for V79 (1.30, CI 1.25-1.36, P=.74) and GS4 (1.42, CI 1.30-1.54, P=.67). No significant dependence of RBE on dose was found for Intrabeam, but RBE decreased at a larger distance (12.7 mm; 9.8 Gy/h). Conclusions: An increased clinically relevant RBE was found for cell irradiation with Intrabeam at depths in the tumor bed targeted by IORT. The reduced RBE values at larger distances may be related to increased repair of sublethal damage during protracted irradiation or to hardening of the photon beam energy.

A New Photometric Study of Ap and Am Stars in the Infrared

Energy Technology Data Exchange (ETDEWEB)

Chen, P. S.; Liu, J. Y.; Shan, H. G., E-mail: chenps@ynao.ac.cn [Yunnan Observatories and Key Laboratory for the Structure and Evolution of Celestial Objects, Chinese Academy of Sciences, Kunming 650011 (China)

2017-05-01

In this paper, 426 well known confirmed Ap and Am stars are photometrically studied in the infrared. The 2MASS, Wide-field Infrared Survey Explorer ( WISE ), and IRAS data are employed to make analyses. The results in this paper have shown that in the 1–3 μ m region over 90% Ap and Am stars have no or little infrared excesses, and infrared radiations in the near-infrared from these stars are probably dominated by the free–free emissions. It is also shown that in the 3–12 μ m region, the majority of Ap stars and Am stars have very similar behavior, i.e., in the W 1– W 2 (3.4–4.6 μ m) region, over half of Ap and Am stars have clear infrared excesses, which are possibly due to the binarity, the multiplicity, and/or the debris disk, but in the W 2– W 3 (4.6–12 μ m) region they have no or little infrared excess. In addition, in the 12–22 μ m region, some of Ap stars and Am stars show the infrared excesses and infrared radiations for these Ap and Am stars are probably due to the free–free emissions. In addition, it is seen that the probability of being the binarity, the multiplicity and/or the debris disk for Am stars is much higher than that for Ap stars. Furthermore, it can be seen that, in general, no relations can be found between infrared colors and spectral types either for Ap stars or for Am stars.

A New Photometric Study of Ap and Am Stars in the Infrared

International Nuclear Information System (INIS)

Chen, P. S.; Liu, J. Y.; Shan, H. G.

2017-01-01

In this paper, 426 well known confirmed Ap and Am stars are photometrically studied in the infrared. The 2MASS, Wide-field Infrared Survey Explorer ( WISE ), and IRAS data are employed to make analyses. The results in this paper have shown that in the 1–3 μ m region over 90% Ap and Am stars have no or little infrared excesses, and infrared radiations in the near-infrared from these stars are probably dominated by the free–free emissions. It is also shown that in the 3–12 μ m region, the majority of Ap stars and Am stars have very similar behavior, i.e., in the W 1– W 2 (3.4–4.6 μ m) region, over half of Ap and Am stars have clear infrared excesses, which are possibly due to the binarity, the multiplicity, and/or the debris disk, but in the W 2– W 3 (4.6–12 μ m) region they have no or little infrared excess. In addition, in the 12–22 μ m region, some of Ap stars and Am stars show the infrared excesses and infrared radiations for these Ap and Am stars are probably due to the free–free emissions. In addition, it is seen that the probability of being the binarity, the multiplicity and/or the debris disk for Am stars is much higher than that for Ap stars. Furthermore, it can be seen that, in general, no relations can be found between infrared colors and spectral types either for Ap stars or for Am stars.

miR-1 is increased in pulmonary hypertension and downregulates Kv1.5 channels in rat pulmonary arteries.

Science.gov (United States)

Mondejar-Parreño, Gema; Callejo, María; Barreira, Bianca; Morales-Cano, Daniel; Esquivel-Ruiz, Sergio; Moreno, Laura; Cogolludo, Angel; Perez-Vizcaino, Francisco

2018-05-02

■The expression of miR-1 is increased in lungs from the Hyp/Su5416 PAH rat model. ■PASMC from this animal model are more depolarised and show decreased expression and activity of Kv1.5. ■miR-1 directly targets Kv1.5 channels, reduces Kv1.5 activity and induces membrane depolarization. ■Antagomir-1 prevents Kv1.5 channel downregulation and the depolarization induced by hypoxia/Su5416 exposition. Impairment of voltage-dependent potassium channel (Kv) plays a central role in the development of cardiovascular diseases, including pulmonary arterial hypertension (PAH). MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression by binding to the 3'-UTR region of specific mRNAs. The aim of this study was to analyze the effects of miR-1 on Kv channel function in pulmonary arteries (PA). Kv channel activity was studied in PA from healthy animals transfected with miR-1 or scrambled-miR. Kv currents were studied using the whole-cell configuration of patch-clamp technique. The characterization of the Kv1.5 currents was performed with the selective inhibitor DPO-1. miR-1 expression was increased and Kv1.5 channels were decreased in lungs from a rat model of PAH induced by hypoxia and Su5416. miR-1 transfection increased cell capacitance, reduced Kv1.5 currents and induced membrane depolarization in isolated pulmonary artery smooth muscle cells (PASMCs). Luciferase reporter assay indicated that KCNA5, which encodes Kv1.5 channels, is a direct target gene of miR-1. Incubation of PA with Su5416 and hypoxia (3% O 2 ) increased miR-1 and induced a decline in Kv1.5 currents, which was prevented by antagomiR-1. In conclusion, these data indicate that miR-1 induces PASMC hypertrophy and reduces the activity and expression of Kv channels, suggesting a pathophysiological role in PAH. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Tank 241-AP-107, grab samples 7AP-97-1, 7AP-97-2 and 7AP-97-3 analytical results for the final report

International Nuclear Information System (INIS)

Steen, F.H.

1997-01-01

This document is the final report for tank 241-AP-107 grab samples. Three grab samples were collected from riser 1 on September 11, 1997. Analyses were performed on samples 7AP-97-1, 7AP-97-2 and 7AP-97-3 in accordance with the Compatibility Grab Sampling and Analysis Plan (TSAP) (Sasaki, 1997) and the Data Quality Objectives for Tank Farms Waste Compatibility Program (DQO) (Rev. 1: Fowler, 1995; Rev. 2: Mulkey and Nuier, 1997). The analytical results are presented in the data summary report (Table 1). A notification was made to East Tank Farms Operations concerning low hydroxide in the tank and a hydroxide (caustic) demand analysis was requested. The request for sample analysis (RSA) (Attachment 2) received for AP-107 indicated that the samples were polychlorinated biphenyl (PCB) suspects. Therefore, prior to performing the requested analyses, aliquots were made to perform PCB analysis in accordance with the 222-S Laboratory administrative procedure, LAP-101-100. The results of this analysis indicated that no PCBs were present at 50 ppm and analysis proceeded as non-PCB samples. The results and raw data for the PCB analysis will be included in a revision to this document. The sample breakdown diagrams (Attachment 1) are provided as a cross-reference for relating the tank farm customer identification numbers with the 222-S Laboratory sample numbers and the portion of sample analyzed

Physiological role of Kv1.3 channel in T lymphocyte cell investigated quantitatively by kinetic modeling.

Directory of Open Access Journals (Sweden)

Panpan Hou

Full Text Available 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.

ELECTROCHEMICAL CORROSION TESTING OF TANKS 241-AN-102 & 241-AP-107 & 241-AP-108 IN SUPPORT OF ULTRASONIC TESTING

Energy Technology Data Exchange (ETDEWEB)

WYRWAS RB; DUNCAN JB

2008-11-20

This report presents the results of the corrosion rates that were measured using electrochemical methods for tanks 241-AN-102 (AN-102), 241-AP-107 (AP 107), and 241-AP-108 (AP-108) performed under test plant RPP-PLAN-38215. The steel used as materials of construction for AN and AP tank farms was A537 Class 1. Test coupons of A537 Class 1 carbon steel were used for corrosion testing in the AN-107, AP-107, and AP-108 tank waste. Supernate will be tested from AN-102, AP-107, and Ap-108. Saltcake testing was performed on AP-108 only.

The Seismic Analysis of 800kV Gas Insulated Switchgear (GIS) for the Dangjin Thermal Plant

Energy Technology Data Exchange (ETDEWEB)

Shin, I.H.; Song, W.P.; Kweon, K.Y. [Hyosung Corporation (Korea)

1999-05-01

800kV GIS (Gas Insulated Switchgear) which was first developed in korea at Dec. 1998 and is going to be installed in the dangjin thermal plant. We checked the stability of 800kV GIS under seismic load. pro-ENGINEER and PATRAN were used for modeling exactly 800kV GIS geometry. The 800kV GIS was modeled as shell elements for the enclosures and beam elements for the conductors and the support insulators. (author). 2 refs., 9 figs., 2 tabs.

Macroscopic magnetic Self assembly

NARCIS (Netherlands)

Löthman, Per Arvid

2018-01-01

Exploring the macroscopic scale's similarities to the microscale is part and parcel of this thesis as reflected in the research question: what can we learn about the microscopic scale by studying the macroscale? Investigations of the environment in which the self-assembly takes place, and the

Sensitivity of screen-film systems

International Nuclear Information System (INIS)

Sandborg, M.; Nilsson, Goergen; Holje, G.

1992-01-01

This report, which has been funded by SSI, presents sensitivity data on the 'second generation' of modern intensifying screens, commercially available at the onset of the investigation. The sensitivity of the screen-film systems was evaluated with 80 kV tube potential and a total filtration of 3.0 mm Al. 20 mm aluminum was used for simulating human tissue, since it gives the same HVL x , as does 25 cm water. Kerma in air, needed to produce a net film density of 1.00 was determined and its inverse, expressed in mGy -1 , was taken as an indicator of the sensitivity; here called the sensitivity class of a screen-film system

Topogram-based automated selection of the tube potential and current in thoraco-abdominal trauma CT - a comparison to fixed kV with mAs modulation alone

International Nuclear Information System (INIS)

Frellesen, Claudia; Stock, Wenzel; Kerl, J.M.; Lehnert, Thomas; Wichmann, Julian L.; Beeres, Martin; Schulz, Boris; Bodelle, Boris; Vogl, Thomas J.; Nau, Christoph; Geiger, Emanuel; Wutzler, Sebastian; Ackermann, Hanns; Bauer, Ralf W.

2014-01-01

To investigate the impact of automated attenuation-based tube potential selection on image quality and exposure parameters in polytrauma patients undergoing contrast-enhanced thoraco-abdominal CT. One hundred patients were examined on a 16-slice device at 120 kV with 190 ref.mAs and automated mA modulation only. Another 100 patients underwent 128-slice CT with automated mA modulation and topogram-based automated tube potential selection (autokV) at 100, 120 or 140 kV. Volume CT dose index (CTDI vol ), dose-length product (DLP), body diameters, noise, signal-to-noise ratio (SNR) and subjective image quality were compared. In the autokV group, 100 kV was automatically selected in 82 patients, 120 kV in 12 patients and 140 kV in 6 patients. Patient diameters increased with higher kV settings. The median CTDI vol (8.3 vs. 12.4 mGy; -33 %) and DLP (594 vs. 909 mGy cm; -35 %) in the entire autokV group were significantly lower than in the group with fixed 120 kV (p < 0.05 for both). Image quality remained at a constantly high level at any selected kV level. Topogram-based automated selection of the tube potential allows for significant dose savings in thoraco-abdominal trauma CT while image quality remains at a constantly high level. (orig.)

Topogram-based automated selection of the tube potential and current in thoraco-abdominal trauma CT - a comparison to fixed kV with mAs modulation alone

Energy Technology Data Exchange (ETDEWEB)

Frellesen, Claudia; Stock, Wenzel; Kerl, J.M.; Lehnert, Thomas; Wichmann, Julian L.; Beeres, Martin; Schulz, Boris; Bodelle, Boris; Vogl, Thomas J. [Clinic of the Goethe University, Department of Diagnostic and Interventional Radiology, Frankfurt (Germany); Nau, Christoph; Geiger, Emanuel; Wutzler, Sebastian [Clinic of the Goethe University, Department of Trauma, Hand and Reconstructive Surgery, Frankfurt (Germany); Ackermann, Hanns [Clinic of the Goethe University, Department of Biostatistics and Mathematical Modelling, Frankfurt (Germany); Bauer, Ralf W. [Clinic of the Goethe University, Department of Diagnostic and Interventional Radiology, Frankfurt (Germany); Klinikum der Goethe-Universitaet, Institut fuer Diagnostische und Interventionelle Radiologie, Frankfurt am Main (Germany)

2014-07-15

To investigate the impact of automated attenuation-based tube potential selection on image quality and exposure parameters in polytrauma patients undergoing contrast-enhanced thoraco-abdominal CT. One hundred patients were examined on a 16-slice device at 120 kV with 190 ref.mAs and automated mA modulation only. Another 100 patients underwent 128-slice CT with automated mA modulation and topogram-based automated tube potential selection (autokV) at 100, 120 or 140 kV. Volume CT dose index (CTDI{sub vol}), dose-length product (DLP), body diameters, noise, signal-to-noise ratio (SNR) and subjective image quality were compared. In the autokV group, 100 kV was automatically selected in 82 patients, 120 kV in 12 patients and 140 kV in 6 patients. Patient diameters increased with higher kV settings. The median CTDI{sub vol} (8.3 vs. 12.4 mGy; -33 %) and DLP (594 vs. 909 mGy cm; -35 %) in the entire autokV group were significantly lower than in the group with fixed 120 kV (p < 0.05 for both). Image quality remained at a constantly high level at any selected kV level. Topogram-based automated selection of the tube potential allows for significant dose savings in thoraco-abdominal trauma CT while image quality remains at a constantly high level. (orig.)

Sensitivity comparison of two L-alanine doped blends to different photon energies

International Nuclear Information System (INIS)

Chen, Felipe; Vega Ramirez, Jose; Nicolucci, Patricia; Baffa, Oswaldo

2008-01-01

Full text: Blends of L-alanine (85% weight proportion) with KI (10%) and with PbI 2 (10%), these last two compounds acting as dopants, and with PVA (5%) acting as binder, were prepared in water at 80 C degrees. A blend of pure L-alanine (95%) with PVA (5%) was also prepared. The three blends were irradiated with photon beams of different energies (120 kV, 60 Co and 10 MV) with a unique dose of 30 Gy to compare their sensitivities for those three energies. EPR spectra of the three irradiated blends were recorded in a K-Band spectrometer (24 GHz) taking aliquots of about 4 mg for each blend. The energy sensitivity of a blend was defined as the peak-to-peak amplitude of its EPR spectrum central line. For the 60 Co energy (1.25 MeV) the blends presented practically the same sensitivity indicating that the presence of the dopants does not affect the sensitivity of L-alanine. For 10 MV X-rays there was an increment (around 20% - 30 %) in sensitivity for the two L-alanine doped blends compared with the pure L-alanine blend (not doped). In the case of 120 kV X-rays, the blends ala+KI and ala+PbI 2 showed an increment of 10 and 20 times, respectively, more sensitivity than the pure L-alanine blend. It is concluded that the dopants KI and PbI 2 produce a great enhance of the L-alanine sensitivity to low-energy photons. For the same dopant's content (10%) in the blend, PbI 2 showed a better performance. These results encourage us to try to enhance the sensitivity of L-alanine even more increasing the dopant's content in the blend. Application of these L-alanine doped blends in the dosimetry in diagnostic radiology could be possible. (author)

Improvements in the computation of balances and localization of commercial losses of electric energy in 0.38-kV networks

International Nuclear Information System (INIS)

Vorotnitskii, V. Z.; Zaslonov, S. V.; Lysyuk, S. S.

2006-01-01

An example of four 0.38-kV overhead distribution lines fed from a 10/0.4-kV transformer substation of the Grodno Electrical Networks (Belarus') and supplying electricity to a cottage area is used for analyzing energy balances and commercial losses in the networks. It is shown that the reliability of such analysis can be ensured by the use of modern software and electronic energy meters recording a retrospective of half-hourly intervals of active and reactive electric energy

Specific Kv1.3 blockade modulates key cholesterol-metabolism-associated molecules in human macrophages exposed to ox-LDL[S

Science.gov (United States)

Yang, Yong; Wang, Yan-Fu; Yang, Xiao-Fang; Wang, Zhao-Hui; Lian, Yi-Tian; Yang, Ying; Li, Xiao-Wei; Gao, Xiang; Chen, Jian; Shu, Yan-Wen; Cheng, Long-Xian; Liao, Yu-Hua; Liu, Kun

2013-01-01

Cholesterol-metabolism-associated molecules, including scavenger receptor class A (SR-A), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), CD36, ACAT1, ABCA1, ABCG1, and scavenger receptor class B type I, can modulate cholesterol metabolism in the transformation from macrophages to foam cells. Voltage-gated potassium channel Kv1.3 has increasingly been demonstrated to play an important role in the modulation of macrophage function. Here, we investigate the role of Kv1.3 in modulating cholesterol-metabolism-associated molecules in human acute monocytic leukemia cell-derived macrophages (THP-1 macrophages) and human monocyte-derived macrophages exposed to oxidized LDL (ox-LDL). Human Kv1.3 and Kv1.5 channels (hKv1.3 and hKv1.5) are expressed in macrophages and form a heteromultimeric channel. The hKv1.3-E314 antibody that we had generated as a specific hKv1.3 blocker inhibited outward delayed rectifier potassium currents, whereas the hKv1.5-E313 antibody that we had generated as a specific hKv1.5 blocker failed. Accordingly, the hKv1.3-E314 antibody reduced percentage of cholesterol ester and enhanced apoA-I-mediated cholesterol efflux in THP-1 macrophages and human monocyte-derived macrophages exposed to ox-LDL. The hKv1.3-E314 antibody downregulated SR-A, LOX-1, and ACAT1 expression and upregulated ABCA1 expression in THP-1 macrophages and human monocyte-derived macrophages. Our results reveal that specific Kv1.3 blockade represents a novel strategy modulating cholesterol metabolism in macrophages, which benefits the treatment of atherosclerotic lesions. PMID:23099443

Macroscopic effects in attosecond pulse generation

International Nuclear Information System (INIS)

Ruchon, T; Varju, K; Mansten, E; Swoboda, M; L'Huillier, A; Hauri, C P; Lopez-Martens, R

2008-01-01

We examine how the generation and propagation of high-order harmonics in a partly ionized gas medium affect their strength and synchronization. The temporal properties of the resulting attosecond pulses generated in long gas targets can be significantly influenced by macroscopic effects, in particular by the intensity in the medium and the degree of ionization which control the dispersion. Under some conditions, the use of gas targets longer than the absorption length can lead to the generation of compressed attosecond pulses. We show these macroscopic effects experimentally, using a 6 mm-long argon-filled gas cell as the generating medium

Macroscopic effects in attosecond pulse generation

Energy Technology Data Exchange (ETDEWEB)

Ruchon, T; Varju, K; Mansten, E; Swoboda, M; L' Huillier, A [Department of Physics, Lund University, PO Box 118, SE-221 00 Lund (Sweden); Hauri, C P; Lopez-Martens, R [Laboratoire d' Optique Appliquee, Ecole Nationale Superieure des Techniques Avancees (ENSTA)-Ecole Polytechnique CNRS UMR 7639, 91761 Palaiseau (France)], E-mail: anne.lhuillier@fysik.lth.se

2008-02-15

We examine how the generation and propagation of high-order harmonics in a partly ionized gas medium affect their strength and synchronization. The temporal properties of the resulting attosecond pulses generated in long gas targets can be significantly influenced by macroscopic effects, in particular by the intensity in the medium and the degree of ionization which control the dispersion. Under some conditions, the use of gas targets longer than the absorption length can lead to the generation of compressed attosecond pulses. We show these macroscopic effects experimentally, using a 6 mm-long argon-filled gas cell as the generating medium.

CIAE 600 kV ns pulse neutron generator

International Nuclear Information System (INIS)

Shen Guanren; Guan Xialing; Chen Hongtao

2001-01-01

The overall composition of CIAE 600 kV ns Pulse Neutron Generator (CPNG) are introduced, and its characteristic, main technological performance and application were also given. CPNG consists of high voltage power supply with highest output voltage 600 kV, direct current 15 mA, stability and ripple ≤0.1%, 2214 mm x 1604 mm x 1504 mm stainless steel high voltage electrode, built in head equipment uniform field accelerating tube, ns pulsed installation, turbomolecular vacuum pump system and drift pipes at 0 degree and 45 degree. Its characteristics are: (1) high current beam; (2) high current beam ns pulsed installation made use of low energy for chopper and high energy for buncher; (3) compactly laid out and simple in structure

On disentanglement of quantum wave functions: Answer to a comment on ''Unified dynamics for microscopic and macroscopic systems''

International Nuclear Information System (INIS)

Ghirardi, G.C.; Rimini, A.; Weber, T.

1987-06-01

It is shown that the assumption of a stochastic localization process for the quantum wave function is essentially different from the suppression of coherence over macroscopic distances arising from the interaction with the environment and allows for a conceptually complete derivation of the classical behaviour of macroscopic bodies. (author). 4 refs

Kv2 Ion Channels Determine the Expression and Localization of the Associated AMIGO-1 Cell Adhesion Molecule in Adult Brain Neurons

Directory of Open Access Journals (Sweden)

Hannah I. Bishop

2018-01-01

Full Text Available Voltage-gated K+ (Kv channels play important roles in regulating neuronal excitability. Kv channels comprise four principal α subunits, and transmembrane and/or cytoplasmic auxiliary subunits that modify diverse aspects of channel function. AMIGO-1, which mediates homophilic cell adhesion underlying neurite outgrowth and fasciculation during development, has recently been shown to be an auxiliary subunit of adult brain Kv2.1-containing Kv channels. We show that AMIGO-1 is extensively colocalized with both Kv2.1 and its paralog Kv2.2 in brain neurons across diverse mammals, and that in adult brain, there is no apparent population of AMIGO-1 outside of that colocalized with these Kv2 α subunits. AMIGO-1 is coclustered with Kv2 α subunits at specific plasma membrane (PM sites associated with hypolemmal subsurface cisternae at neuronal ER:PM junctions. This distinct PM clustering of AMIGO-1 is not observed in brain neurons of mice lacking Kv2 α subunit expression. Moreover, in heterologous cells, coexpression of either Kv2.1 or Kv2.2 is sufficient to drive clustering of the otherwise uniformly expressed AMIGO-1. Kv2 α subunit coexpression also increases biosynthetic intracellular trafficking and PM expression of AMIGO-1 in heterologous cells, and analyses of Kv2.1 and Kv2.2 knockout mice show selective loss of AMIGO-1 expression and localization in neurons lacking the respective Kv2 α subunit. Together, these data suggest that in mammalian brain neurons, AMIGO-1 is exclusively associated with Kv2 α subunits, and that Kv2 α subunits are obligatory in determining the correct pattern of AMIGO-1 expression, PM trafficking and clustering.

Decoherence bypass of macroscopic superpositions in quantum measurement

International Nuclear Information System (INIS)

Spehner, Dominique; Haake, Fritz

2008-01-01

We study a class of quantum measurement models. A microscopic object is entangled with a macroscopic pointer such that a distinct pointer position is tied to each eigenvalue of the measured object observable. Those different pointer positions mutually decohere under the influence of an environment. Overcoming limitations of previous approaches we (i) cope with initial correlations between pointer and environment by considering them initially in a metastable local thermal equilibrium, (ii) allow for object-pointer entanglement and environment-induced decoherence of distinct pointer readouts to proceed simultaneously, such that mixtures of macroscopically distinct object-pointer product states arise without intervening macroscopic superpositions, and (iii) go beyond the Markovian treatment of decoherence. (fast track communication)

Aberration-corrected STEM/TEM imaging at 15 kV

International Nuclear Information System (INIS)

Sasaki, Takeo; Sawada, Hidetaka; Hosokawa, Fumio; Sato, Yuta; Suenaga, Kazu

2014-01-01

The performance of aberration-corrected (scanning) transmission electron microscopy (S/TEM) at an accelerating voltage of 15 kV was evaluated in a low-voltage microscope equipped with a cold-field emission gun and a higher-order aberration corrector. Aberrations up to the fifth order were corrected by the aberration measurement and auto-correction system using the diffractogram tableau method in TEM and Ronchigram analysis in STEM. TEM observation of nanometer-sized particles demonstrated that aberrations up to an angle of 50 mrad were compensated. A TEM image of Si[110] exhibited lattice fringes with a spacing of 0.192 nm, and the power spectrum of the image showed spots corresponding to distances of 0.111 nm. An annular dark-field STEM image of Si[110] showed lattice fringes of (111) and (22¯0) planes corresponding to lattice distances of 0.314 nm and 0.192 nm, respectively. At an accelerating voltage of 15 kV, the developed low-voltage microscope achieved atomic-resolution imaging with a small chromatic aberration and a large uniform phase. - Highlights: • Aberration-corrected STEM/TEM imaging at 15 kV demonstrated lattice fringes of Si[110] single crystal with a spacing of 0.192 nm. • To achieve this performance at a lower accelerating voltage, uniform phase area over 50 mrad is mandatory in Ronchigram and Diffractogram tableau. • This means a higher-order aberration of six-fold astigmatism should be compensated. • In addition, decreasing the effect of chromatic aberration plays an important role for improving the performance of linear scattering component at 15 kV TEM

Children born to SLE and APS mothers.

Science.gov (United States)

Nalli, C; Iodice, A; Andreoli, L; Lojacono, A; Motta, M; Fazzi, E; Tincani, A

2014-10-01

Systemic lupus erythematosus (SLE) and antiphospholipid antibody syndrome (APS) are autoimmune diseases that affect women of childbearing age. Pregnancies in these patients carry several complications such as prematurity. Maternal IgG antiphospholipid antibodies (aPL) can cross the placenta but they don't generally cause any neonatal thrombotic event. Because of the incompleteness of the fetal blood-brain barrier, aPL could theoretically reach the fetal brain. Whether this can have an effect on brain development is still under investigation. Some studies performed in children of patients with SLE and/or APS showed an increased number of learning disabilities without impairment in intelligence level. The objectives of this article are to evaluate the neurodevelopment outcome in 30 children (median age 9 years) born to mothers with SLE and/or APS with IgG anti-beta2-glycoprotein I during the third trimester of pregnancy and found positive for the same antibodies at birth. A neurological physical exam was performed in all children. We submitted some questionnaires to the mothers: the Child Behavior CheckList (CBCL) and a homemade set of questions obtained by a team composed of rheumatologists and pediatric neurologists. Intellectual functioning was determined by the Wechsler scale for corrected age. In all children neurological physical exam and intelligence levels were found to be normal but mild behavior disorders and history of neurological manifestations were shown in three children. Offspring of patients with SLE and/or APS are generally healthy. We and others observed the occurrence of minor neurological disorders that might be related to maternal disease or to prematurity. The limited number of the available data on this sensitive issue supports the need for further studies. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

A continuous acceleration tube of ions under 200 KV; Un tube d'acceleration continue d'ions sous 200 KV

Energy Technology Data Exchange (ETDEWEB)

Mongodin, G [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1954-07-01

The realization of an Van de Graaff accelerator required, for the preliminary studies, the construction of a small proton accelerator, functioning at 200 kV in order to resolve some parasitic effects inherent to the accelerators tubes. The aim of this report is to describe the different organs of the accelerator tube, to explain the operating system and to encode their characteristics. The report first presents the ion source and the beam buncher permitting to inject in the accelerator tube particles of about 9 kV and very batched in a thin beam of circular section. Then the study explain the tube characteristics considered like optic system. A method to obtain precise calculation of particle trajectories is exposed. Aberrations of the system were discussed and balance of the currents on all electrodes inside the tube for different regimes of working were provided. The influence of the residual pressure in the tube were explained. The report finally ends on a part of the fundamental problem of the straining occurring inside the tubes accelerators under high tension. (M.B.) [French] La realisation d n accelerateur du type Van de Graaff a necessite, entre autres etudes preliminaires, la construction d'un petit accelerateur de protons, fonctionnant sous 200 kV afin d'eclaircir certains effets parasites propres aux tubes accelerateurs. L'objet de ce rapport est de decrire les differents organes du tube accelerateur, d'en expliquer le fonctionnement et de chiffrer leurs caracteristiques. Le memoire presente d'abord la source d'ions et le canon permettant d'injecter dans le tube accelerateur des particules de 9 kV environ et bien groupees dans un faisceau fin de section circulaire. Puis il passe a l'etude du tube considere comme systeme optique. Une methode utilisee pour le calcul precis des trajectoires des particules y est exposee. Il aborde le probleme des aberrations de ce systeme et fournit par la suite le bilan des courants sur toutes les electrodes a l

Nonequilibrium work relation in a macroscopic system

International Nuclear Information System (INIS)

Sughiyama, Yuki; Ohzeki, Masayuki

2013-01-01

We reconsider a well-known relationship between the fluctuation theorem and the second law of thermodynamics by evaluating stochastic evolution of the density field (probability measure valued process). In order to establish a bridge between microscopic and macroscopic behaviors, we must take the thermodynamic limit of a stochastic dynamical system following the standard procedure in statistical mechanics. The thermodynamic path characterizing a dynamical behavior in the macroscopic scale can be formulated as an infimum of the action functional for the stochastic evolution of the density field. In our formulation, the second law of thermodynamics can be derived only by symmetry of the action functional without recourse to the Jarzynski equality. Our formulation leads to a nontrivial nonequilibrium work relation for metastable (quasi-stationary) states, which are peculiar in the macroscopic system. We propose a prescription for computing the free energy for metastable states based on the resultant work relation. (paper)

Task Force on Catastrophic Antiphospholipid Syndrome (APS) and Non-criteria APS Manifestations (II): thrombocytopenia and skin manifestations.

Science.gov (United States)

Cervera, R; Tektonidou, M G; Espinosa, G; Cabral, A R; González, E B; Erkan, D; Vadya, S; Adrogué, H E; Solomon, M; Zandman-Goddard, G; Shoenfeld, Y

2011-02-01

The objectives of the 'Task Force on Catastrophic Antiphospholipid Syndrome (APS) and Non-criteria APS Manifestations' were to assess the clinical utility of the international consensus statement on classification criteria and treatment guidelines for the catastrophic APS, to identify and grade the studies that analyze the relationship between the antiphospholipid antibodies and the non-criteria APS manifestations, and to present the current evidence regarding the accuracy of these non-criteria APS manifestations for the detection of patients with APS. This article summarizes the studies analyzed on thrombocytopenia and skin manifestations, and presents the recommendations elaborated by the Task Force after this analysis.

100 kV reliable accurately-synchronized spark gap

International Nuclear Information System (INIS)

Bosamykin, V.S.; Gerasimov, A.I.; Zenkov, D.I.

1987-01-01

100 kV three-electrode spark gap filled with 40% SF 6 +60% N 2 mixture under the pressure of ∼ 1 MPa, which has spread Δt ≤ ± 5 ns of operating time delay in the range of 10 4 triggerings and commutation energy of 2.5 kJ, providing electric strength is 100%, is described; at 10 kJ Δt is less than ± 10 ns for 10 3 triggerings. Parallel connection of 16 groups, each consisting of 5 spark gaps with series connection, electric strength being 100%, in the pulse charging unit of Arkadiev-Marx generator being in operation for several years manifested their high efficiency; mutual group spread is ≤ ± 15 ns

Promotion of Homologous Recombination and Genomic Stability byRAD51AP1 via RAD51 Recombinase Enhancement

Energy Technology Data Exchange (ETDEWEB)

Wiese, Claudia; Dray, Eloise; Groesser, Torsten; San Filippo,Joseph; Shi, Idina; Collins, David W.; Tsai, Miaw-Sheue; Williams,Gareth; Rydberg, Bjorn; Sung, Patrick; Schild, David

2007-04-11

Homologous recombination (HR) repairs chromosome damage and is indispensable for tumor suppression in humans. RAD51 mediates the DNA strand pairing step in HR. RAD51AP1 (RAD51 Associated Protein 1) is a RAD51-interacting protein whose function has remained elusive. Knockdown of RAD51AP1 in human cells by RNA interference engenders sensitivity to different types of genotoxic stress. Moreover, RAD51AP1-depleted cells are impaired for the recombinational repair of a DNA double-strand break and exhibit chromatid breaks both spontaneously and upon DNA damaging treatment. Purified RAD51AP1 binds dsDNA and RAD51, and it greatly stimulates the RAD51-mediated D-loop reaction. Biochemical and cytological results show that RAD51AP1 functions at a step subsequent to the assembly of the RAD51-ssDNA nucleoprotein filament. Our findings provide the first evidence that RAD51AP1 helps maintain genomic integrity via RAD51 recombinase enhancement.

Laser drive development for the APS Dynamic Compression Sector

Science.gov (United States)

Lagrange, Thomas; Swift, Damian; Reed, Bryan; Bernier, Joel; Kumar, Mukul; Hawreliak, James; Eggert, Jon; Dixit, Sham; Collins, Gilbert

2013-06-01

The Dynamic Compression Sector (DCS) at the APS synchrotron offers unprecedented possibilities for x-ray diffraction and scattering measurements in-situ during dynamic loading, including single-shot data collection with x-ray energies high enough (tens of kV) to study high-Z samples in transmission as well as reflection. Dynamic loading induced by laser ablation is an important component of load generation, as the duration, strain rate, and pressure can be controlled via the energy, spot size, and pulse shape. Using radiation hydrodynamics simulations, validated by experiments at several laser facilities, we have investigated the relationship between irradiance history and pressure for ablative loads designed to induce shock and ramp loading in the nanosecond to microsecond range, and including free ablation and also ablation confined by a transparent substrate. We have investigated the effects of lateral release, which constrains the minimum diameter of the focal spot for a given drive duration. In this way, we are able to relate the desired drive conditions to the total laser energy needed, which dictates the laser technologies suitable for a given type of experiment. This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

The voltage-gated potassium channel subunit, Kv1.3, is expressed in epithelia

DEFF Research Database (Denmark)

Grunnet, Morten; Rasmussen, Hanne B; Hay-Schmidt, Anders

2003-01-01

The Shaker-type voltage-gated potassium channel, Kv1.3, is believed to be restricted in distribution to lymphocytes and neurons. In lymphocytes, this channel has gained intense attention since it has been proven that inhibition of Kv1.3 channels compromise T lymphocyte activation. To investigate...

Development of a 300-kV Marx generator and its application to drive ...

Indian Academy of Sciences (India)

Accelerator and Pulse Power Division, Bhabha Atomic Research Centre, ... anode gap of 7·5 mm, an REB having beam voltage 160 kV and duration 150 ns ... lowest stage has a triggered SG which is closed by a 6 kV pulse obtained with the ...

Construction of a 500 kV aerial power line in East Java

Energy Technology Data Exchange (ETDEWEB)

Kaeufl, O; Paschen, R; Kummermehr, R

1987-10-12

The authors report on the technical preparations and the construction of a 500 kv, four-bundle power line with a pylon tonnage of approximately 10,000 t of steel and a route length of 251 km in Indonesia. Due to the difficult terrain conditions, the sensitive infrastructure and the extremely short construction period, this project was a special technological challenge. Initially, the authors explain the technical planning of Brown Boveri with emphasis on foundations and assembly. As part of this tailor-made concept new technological solutions were used. They were instrumental in the successful completion of the project in only 19 months by the end of 1986 to the complete satisfaction of the customer. The authors also comment on the pracitcal experiences gained during the construction.

Thrombotic recurrences and bleeding events in APS vascular patients: a review from the literature and a comparison with the APS Piedmont Cohort.

Science.gov (United States)

Bazzan, M; Vaccarino, A; Stella, S; Bertero, M T; Carignola, R; Montaruli, B; Roccatello, D; Shoenfeld, Y

2013-06-01

In APS vascular patients, thrombotic recurrences are more frequent than in non-APS thrombotic patients. To better define this clinical setting, a systematic review of the literature after 1999 was performed: 8 cohort studies (including the recent APS Piedmont Cohort) and 6 intervention studies were selected and evaluated. Thrombotic recurrences, bleeding events, therapeutic strategies, antiphospholipid (aPL) profile, inherited and acquired risk factors (when present) were calculated and compared. Emerging risk factors for thrombotic recurrences include withdrawal of oral anticoagulant therapy (OAT), high intensity OAT (INR range 3-4), aPL profile (triple positivity, Miyakis types 1 and 2a profiles) and association with inherited or acquired pro-thrombotic risk factors. Moreover, there are evidences that high risk (mainly for aPL profile) APS vascular patients have a high recurrence rate in spite of correct OAT treatment. Clinical trials in this clinical setting are needed. Copyright © 2012 Elsevier B.V. All rights reserved.

Trafficking of Kv2.1 Channels to the Axon Initial Segment by a Novel Nonconventional Secretory Pathway

DEFF Research Database (Denmark)

Jensen, Camilla Stampe; Watanabe, Shoji; Stas, Jeroen Ingrid

2017-01-01

the localization of Kv2.1 in these two different membrane compartments in cultured rat hippocampal neurons of mixed sex. Our data uncover a unique ability of Kv2.1 channels to use two molecularly distinct trafficking pathways to accomplish this. Somatodendritic Kv2.1 channels are targeted by the conventional...... secretory pathway, whereas axonal Kv2.1 channels are targeted by a nonconventional trafficking pathway independent of the Golgi apparatus. We further identified a new AIS trafficking motif in the C-terminus of Kv2.1, and show that putative phosphorylation sites in this region are critical for the restricted.......SIGNIFICANCE STATEMENT Our study uncovered a novel mechanism that targets the Kv2.1 voltage-gated potassium channel to two distinct trafficking pathways and two distinct subcellular destinations: the somatodendritic plasma membrane and that of the axon initial segment. We also identified a distinct motif, including...

Design and Control of a 13.2 kV/10 kVA Single-Phase Solid-State-Transformer with 1.7 kV SiC Devices

Directory of Open Access Journals (Sweden)

Jeong-Woo Lim

2018-01-01

Full Text Available This paper describes the power stage design, control, and performance evaluation of a 13.2 kV/10 kVA solid-state-transformer (SST for a power distribution system. The proposed SST consists of 10 modules where each individual module contains a unidirectional three-level power factor correction (PFC converter for the active-front-end (AFE stage and an LLC resonant converter for the isolated DC-DC stage. The operating principles of the converters are analyzed and the modulation and the control schemes for the entire module are described in detail. The DC-link voltage imbalance is also less than other SST topologies due to the low number of uncontrollable switching states. In order to simplify the control of the power stage, a modulation strategy for the AFE stage is proposed, and the modulation frequency of the LLC converter is also fixed. In addition, a compensation algorithm is suggested to eliminate the current measurement offset in the AFE stage. The proposed SST achieves the unity power factor at the input AC current regardless of the reactive or nonlinear load and a low voltage regulation at the AC output. In order to verify the effectiveness of the SST, the 13.2 kV/10 kV SST prototype is built and tested. Both the simulation and the experimental results under actual 13.2 kV line show the excellent performance of the proposed SST scheme.

Comparative analysis between radiographic views for knee osteoarthrosis (bipedal AP versus monopedal AP

Directory of Open Access Journals (Sweden)

Rodrigo Pires e Albuquerque

2013-08-01

Full Text Available OBJECTIVE: A comparative analysis by applying the criteria of the original classification Ahlbäck in the anteroposterior (AP bipedal knee in extension and anteroposterior (AP monopodal knee in symptomatic knee arthrosis. With this analysis we intend to observe the agreement, any advantage or difference between the incidence and degree of joint involvement between the orthopedic surgeons and radiologists with the referring physician. METHODS: From January 2012 to March 2012, was a prospective study of 60 symptomatic arthrosis knees (60 patients, clinically selected group of outpatient knee and radiographic proposals submitted to the search. Of the 60 patients, 39 were female and 21 male, mean age 64 years (ranging from 50 to 84 years. Of the 60 knees studied, 37 corresponded to the right side and 23 on the left side. Statistical analysis was performed by Kappa statistics, which evaluates the interobserver agreement for qualitative data. RESULTS: According to the scale of Ahlbäck, there was a significant agreement (p < 0.0001 intra-observer in the classification of knee osteoarthritis among the five evaluators. There was a significant agreement (p < 0.0001 with inter-observer referring physician in the incidence of AP monopodal and AP bipedal for the four raters. CONCLUSION: The study found no difference between the incidence in the AP monopodal versus AP bipedal in osteoarthritis of the knee.

AIRE variations in Addison's disease and autoimmune polyendocrine syndromes (APS): partial gene deletions contribute to APS I.

Science.gov (United States)

Bøe Wolff, A S; Oftedal, B; Johansson, S; Bruland, O; Løvås, K; Meager, A; Pedersen, C; Husebye, E S; Knappskog, P M

2008-03-01

Autoimmune Addison's disease (AAD) is often associated with other components in autoimmune polyendocrine syndromes (APS). Whereas APS I is caused by mutations in the AIRE gene, the susceptibility genes for AAD and APS II are unclear. In the present study, we investigated whether polymorphisms or copy number variations in the AIRE gene were associated with AAD and APS II. First, nine SNPs in the AIRE gene were analyzed in 311 patients with AAD and APS II and 521 healthy controls, identifying no associated risk. Second, in a subgroup of 25 of these patients, AIRE sequencing revealed three novel polymorphisms. Finally, the AIRE copy number was determined by duplex quantitative PCR in 14 patients with APS I, 161 patients with AAD and APS II and in 39 healthy subjects. In two Scandinavian APS I patients previously reported to be homozygous for common AIRE mutations, we identified large deletions of the AIRE gene covering at least exon 2 to exon 8. We conclude that polymorphisms in the AIRE gene are not associated with AAD and APS II. We further suggest that DNA analysis of the parents of patients found to be homozygous for mutations in AIRE, always should be performed.

The schizophrenia-associated Kv11.1-3.1 isoform results in reduced current accumulation during repetitive brief depolarizations.

Directory of Open Access Journals (Sweden)

Juliane Heide

Full Text Available Recent genome wide association studies identified a brain and primate specific isoform of a voltage-gated potassium channel, referred to as Kv11.1-3.1, which is significantly associated with schizophrenia. The 3.1 isoform replaces the first 102 amino acids of the most abundant isoform (referred to as Kv11.1-1A with six unique amino acids. Here we show that the Kv11.1-3.1 isoform has faster rates of channel deactivation but a slowing of the rates of inactivation compared to the Kv11.1-1A isoform. The Kv11.1-3.1 isoform also has a significant depolarizing shift in the voltage-dependence of steady-state inactivation. The consequence of the altered gating kinetics is that there is lower current accumulation for Kv11.1-3.1 expressing cells during repetitive action potential firing compared to Kv11.1-1A expressing cells, which in turn will result in longer lasting trains of action potentials. Increased expression of Kv11.1-3.1 channels in the brain of schizophrenia patients might therefore contribute to disorganized neuronal firing.

Parameter design and performance simulation of a 10 kV voltage compensation type active superconducting fault current limiter

International Nuclear Information System (INIS)

Chen, L.; Tang, Y.J.; Song, M.; Shi, J.; Ren, L.

2013-01-01

Highlights: •For a practical 10 kV system, the 10 kV active SFCL’s basic parameters are designed. •Under different fault conditions, the 10 kV active SFCL’s performances are simulated. •The designed 10 kV active SFCL’s engineering feasibility is discussed preliminarily. -- Abstract: Since the introduction of superconducting fault current limiter (SFCL) into electrical distribution system may be a good choice with economy and practicability, the parameter design and current-limiting characteristics of a 10 kV voltage compensation type active SFCL are studied in this paper. Firstly, the SFCL’s circuit structure and operation principle are presented. Then, taking a practical 10 kV distribution system as its application object, the SFCL’s basic parameters are designed to meet the system requirements. Further, using MATLAB, the detailed current-limiting performances of the 10 kV active SFCL are simulated under different fault conditions. The simulation results show that the active SFCL can deal well with the faults, and the parameter design’s suitability can be testified. At the end, in view of the engineering feasibility of the 10 kV active SFCL, some preliminary discussions are carried out

Macroscopic nonclassical-state preparation via postselection

Science.gov (United States)

Montenegro, Víctor; Coto, Raúl; Eremeev, Vitalie; Orszag, Miguel

2017-11-01

Macroscopic quantum superposition states are fundamental to test the classical-quantum boundary and present suitable candidates for quantum technologies. Although the preparation of such states has already been realized, the existing setups commonly consider external driving and resonant interactions, predominantly by considering Jaynes-Cummings-like and beam-splitter-like interactions, as well as the nonlinear radiation pressure interaction in cavity optomechanics. In contrast to previous works on the matter, we propose a feasible probabilistic scheme to generate a macroscopic mechanical qubit, as well as phononic Schrödinger's cat states with no need of any energy exchange with the macroscopic mechanical oscillator. Essentially, we investigate an open dispersive spin-mechanical system in the absence of any external driving under nonideal conditions, such as the detrimental effects due to the oscillator and spin energy losses in a thermal bath at nonzero temperature. In our work, we show that the procedure to generate the mechanical qubit state is solely based on spin postselection in the weak to moderate coupling regime. Finally, we demonstrate that the mechanical superposition is related to the amplification of the mean values of the mechanical quadratures as they maximize the quantum coherence.

Scanner-based macroscopic color variation estimation

Science.gov (United States)

Kuo, Chunghui; Lai, Di; Zeise, Eric

2006-01-01

Flatbed scanners have been adopted successfully in the measurement of microscopic image artifacts, such as granularity and mottle, in print samples because of their capability of providing full color, high resolution images. Accurate macroscopic color measurement relies on the use of colorimeters or spectrophotometers to provide a surrogate for human vision. The very different color response characteristics of flatbed scanners from any standard colorimetric response limits the utility of a flatbed scanner as a macroscopic color measuring device. This metamerism constraint can be significantly relaxed if our objective is mainly to quantify the color variations within a printed page or between pages where a small bias in measured colors can be tolerated as long as the color distributions relative to the individual mean values is similar. Two scenarios when converting color from the device RGB color space to a standardized color space such as CIELab are studied in this paper, blind and semi-blind color transformation, depending on the availability of the black channel information. We will show that both approaches offer satisfactory results in quantifying macroscopic color variation across pages while the semi-blind color transformation further provides fairly accurate color prediction capability.

Classical behaviour of macroscopic bodies and quantum measurements

International Nuclear Information System (INIS)

Ghirardi, G.; Rimini, A.; Weber, T.

1986-01-01

This report describes a recent attempt of giving a consistent and unified description of microscopic and macroscopic phenomena. The model presented in this paper exhibits the nice features of leaving unaltered the quantum description of microsystems and of accounting for the classical behaviour of the macroscopic objects when their dynamical evolution is consistently deduced from the dynamics of their elementary constituents

Assessments of macroscopicity for quantum optical states

DEFF Research Database (Denmark)

Laghaout, Amine; Neergaard-Nielsen, Jonas Schou; Andersen, Ulrik Lund

2015-01-01

With the slow but constant progress in the coherent control of quantum systems, it is now possible to create large quantum superpositions. There has therefore been an increased interest in quantifying any claims of macroscopicity. We attempt here to motivate three criteria which we believe should...... enter in the assessment of macroscopic quantumness: The number of quantum fluctuation photons, the purity of the states, and the ease with which the branches making up the state can be distinguished. © 2014....

Nuclear fission as a macroscopic quantum tunneling

International Nuclear Information System (INIS)

Takigawa, N.

1995-01-01

We discuss nuclear fission from the point of view of a macroscopic quantum tunneling, one of whose major interests is to study the effects of environments on the tunneling rate of a macroscopic variable. We show that a vibrational excitation of the fissioning nucleus significantly enhances the fission rate. We show this effect by two different methods. The one is to treat the vibrational excitation as an environmental degree of freedom, the other treats the fission as a two dimensional quantum tunneling. (author)

Deleting the accessory subunit KChIP2 results in loss of I(to,f) and increased I(K,slow) that maintains normal action potential configuration

DEFF Research Database (Denmark)

Thomsen, Morten B; Sosunov, Eugene A; Anyukhovsky, Evgeny P

2008-01-01

BACKGROUND: Four voltage-gated potassium currents, I(to,f) (K(V)4.2), I(to,s) (K(V)1.4), I(K,slow) (K(V)1.5+K(V)2.1), and I(SS) (TASK1), govern murine ventricular repolarization. Although the accessory subunit KChIP2 influences I(to,f) expression, in preliminary experiments we found that action...... potential duration (APD) is maintained in KChIP2 knockout mice. OBJECTIVE: We tested the role of KChIP2 in regulating APD and studied the underlying ionic currents. METHODS: We used microelectrode techniques, whole-cell patch clamp studies, and real-time polymerase chain reaction amplification...... to characterize ventricular repolarization and its determinants in wild-type and KChIP2(-/-) mice. RESULTS: Despite comparable baseline action potentials, APD was more markedly prolonged by 4-aminopyridine (4-AP) in KChIP2(-/-) preparations. Peak K(+) current densities were similar in wild-type and KChIP2...

SEU-hardened design for shift register in CMOS APS

International Nuclear Information System (INIS)

Meng Liya; Liu Zedong; Hu Dajiang; Wang Qingxiang

2012-01-01

The inverter-based quasi-static shift register in CMOS APS, which is used in ionizing radiation environment, is susceptible to single event upset (SEU), thus affecting the CMOS active pixel sensor (APS) working. The analysis of the SEU for inverter-based quasi-static shift register concludes that the most sensitive node to single event transient (SET) exists in the input of inverter, and the threshold voltage and capacitance of input node of inverter determine the capability of anti-SEU. A new method was proposed, which replaced the inverter with Schmitt trigger in shift register. Because there is a hysteresis on voltage transfer characteristic of Schmitt trigger, there is high flip threshold, thus better capability of anti-SEU can be achieved. Simulation results show that the anti-SEU capability of Schmitt trigger is 10 times more than that of inverter. (authors)

Conversion of light into macroscopic helical motion

Science.gov (United States)

Iamsaard, Supitchaya; Aßhoff, Sarah J.; Matt, Benjamin; Kudernac, Tibor; Cornelissen, Jeroen J. L. M.; Fletcher, Stephen P.; Katsonis, Nathalie

2014-03-01

A key goal of nanotechnology is the development of artificial machines capable of converting molecular movement into macroscopic work. Although conversion of light into shape changes has been reported and compared to artificial muscles, real applications require work against an external load. Here, we describe the design, synthesis and operation of spring-like materials capable of converting light energy into mechanical work at the macroscopic scale. These versatile materials consist of molecular switches embedded in liquid-crystalline polymer springs. In these springs, molecular movement is converted and amplified into controlled and reversible twisting motions. The springs display complex motion, which includes winding, unwinding and helix inversion, as dictated by their initial shape. Importantly, they can produce work by moving a macroscopic object and mimicking mechanical movements, such as those used by plant tendrils to help the plant access sunlight. These functional materials have potential applications in micromechanical systems, soft robotics and artificial muscles.

Autoantibody profiling in APS.

Science.gov (United States)

Roggenbuck, D; Somma, V; Schierack, P; Borghi, M O; Meroni, P L

2014-10-01

The international consensus for the classification of antiphospholipid syndrome (APS) requires clinical and laboratory criteria to be considered at an equal level for diagnosing APS. Thus, detection of antiphospholipid antibodies (aPL) being a hallmark of APS has been the object of intensive investigation over the past 40 years. However, appropriate detection of aPL still remains a laboratory challenge due to their heterogeneity comprising autoantibodies reactive to different phospholipid-binding plasma proteins, such as beta-2 glycoprotein I (β2GPI) and prothrombin. The relevance of aPL interacting with phospholipids other than cardiolipin (CL, diphosphatidylglycerol), such as phosphatidylserine (PS), remains elusive with regard to the diagnosis of APS. Recently, the concept of aPL profiling has been introduced to assess the risk of thrombotic complications in patients with APS. New assay techniques, apart from enzyme-linked immunosorbent assays (ELISAs) recommended by the international consensus for the classification of APS, have been proposed for multiplexing of aPL testing. Line immunoassays (LIAs) employing a novel hydrophobic solid phase for the simultaneous detection of different aPL seem to be an intriguing alternative. We evaluated a novel multiplex LIA employing a hydrophobic membrane coated with different phospholipid (PL)-binding proteins or PLs. The performance characteristics of this new multiplexing assay technique demonstrated its usefulness for aPL profiling. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Crystallization and preliminary X-ray diffraction studies of the tetramerization domain derived from the human potassium channel Kv1.3

International Nuclear Information System (INIS)

Winklmeier, Andreas; Weyand, Michael; Schreier, Christina; Kalbitzer, Hans Robert; Kremer, Werner

2009-01-01

The tetramerization domain of human Kv1.3 was cloned, expressed, purified and crystallized. The crystals belonged to space group I4 and diffracted to 1.2 Å resolution using synchrotron radiation. The tetramerization domain (T1 domain) derived from the voltage-dependent potassium channel Kv1.3 of Homo sapiens was recombinantly expressed in Escherichia coli and purified. The crystals were first grown in an NMR tube in 150 mM potassium phosphate pH 6.5 in the absence of additional precipitants. The crystals showed I4 symmetry characteristic of the naturally occurring tetrameric assembly of the single subunits. A complete native data set was collected to 1.2 Å resolution at 100 K using synchrotron radiation

Physico-chemical profiles of the wobble ↔ Watson-Crick G*·2AP(w) ↔ G·2AP(WC) and A·2AP(w) ↔ A*·2AP(WC) tautomerisations: a QM/QTAIM comprehensive survey.

Science.gov (United States)

Brovarets', Ol'ha O; Voiteshenko, Ivan S; Hovorun, Dmytro M

2017-12-20

This study is intended to clarify in detail the tautomeric transformations of the wobble (w) G*·2AP(w) and A·2AP(w) nucleobase mispairs involving 2-aminopurine (2AP) into the Watson-Crick (WC) G·2AP(WC) and A*·2AP(WC) base mispairs (asterisks denote mutagenic tautomers of the DNA bases), respectively, by quantum-mechanical methods and Bader's Quantum Theory of Atoms in Molecules. Our previously reported methodology has been used, which allows the evolution of the physico-chemical parameters to be tracked along the entire internal reaction coordinate (IRC), not exclusively in the stationary states of these reactions. These biologically important G*·2AP(w) ↔ G·2AP(WC) and A·2AP(w) ↔ A*·2AP(WC) w ↔ WC tautomerisations, which are involved in mutagenic tautomerically-conformational pathways, determine the origin of the transitions and transversions induced by 2AP. In addition, it is established that they proceed through planar, highly stable, zwitterionic transition states and they exhibit similar physico-chemical profiles and stages of sequential intrapair proton transfer, followed by spatial rearrangement of the nucleobases relative to each other within the base pairs. These w ↔ WC tautomerisations occur non-dissociatively and are accompanied by a significant alteration in geometry (from wobble to Watson-Crick and vice versa) and redistribution of the specific intermolecular interactions, which can be divided into 10 patterns including AHB H-bonds and loosened A-H-B covalent bridges along the IRC of tautomerisation. Based on the redistribution of the geometrical and electron-topological parameters of the intrapair hydrogen bonds, exactly 9 key points have been allocated to characterize the evolution of these reactions.

Survey of familial glioma and role of germline p16INK4A/p14ARF and p53 mutation

DEFF Research Database (Denmark)

Robertson, Lindsay B; Armstrong, Georgina N; Olver, Bianca D

2010-01-01

There is increasing recognition of familial propensity to glioma as a distinct clinical entity beyond a few rare syndromes; however its genetic basis is poorly understood. The role of p16(INK4A)/p14(ARF) and p53 mutations in sporadic glioma provides a strong rationale for investigating germline m...

40-kV, 25-ms neutral-beam power supply for TMX

International Nuclear Information System (INIS)

Leavitt, G.A.

1977-01-01

Modifications are described to upgrade the neutral-beam power supply for the TMX from 40 kV, 10 ms to 40 kV, 25 ms. The redesign of the accel and suppressor power supplies to achieve separation of the high-voltage and control sections, operation of the arc pulse lines in series, operation of the arc pulse lines in a noisy environment with SCR trigger and crowbar, and modifications to the electrolytic storage banks are discussed

Prospective ECG-triggered axial CT at 140-kV tube voltage improves coronary in-stent restenosis visibility at a lower radiation dose compared with conventional retrospective ECG-gated helical CT

Energy Technology Data Exchange (ETDEWEB)

Horiguchi, Jun; Fujioka, Chikako; Kiguchi, Masao; Kohno, Shingo [Hiroshima University Hospital, Department of Clinical Radiology, Hiroshima (Japan); Yamamoto, Hideya; Kitagawa, Toshiro [Hiroshima University, Department of Molecular and Internal Medicine, Division of Clinical Medical Science, Programs for Applied Biomedicine, Graduate School of Biomedical Sciences, Hiroshima (Japan); Ito, Katsuhide [Hiroshima University, Department of Radiology, Division of Medical Intelligence and Informatics, Programs for Applied Biomedicine, Graduate School of Biomedical Sciences, Hiroshima (Japan)

2009-10-15

The purpose of this study was to compare coronary 64-slice CT angiography (CTA) protocols, specifically prospective electrocardiograph (ECG)-triggered and retrospective ECG-gated CT acquisition performed using a tube voltage of 140 kV and 120 kV, regarding intracoronary stent imaging. Coronary artery stents (n=12) with artificial in-stent restenosis (50% luminal reduction, 40 HU) on a cardiac phantom were examined by CT at heart rates of 50-75 beats per minute (bpm). The subjective visibility of in-stent restenosis was evaluated with a three-point scale (1 clearly visible, 2 visible, and 3 not visible), and artificial lumen narrowing [(inner stent diameter - measured lumen diameter)/inner stent diameter], lumen attenuation increase ratio [(in-stent attenuation - coronary lumen attenuation)/coronary lumen attenuation], and signal-to-noise ratio of in-stent lumen were determined. The effective dose was estimated. The artificial lumen narrowing (mean 43%), the increase of lumen attenuation (mean 46%), and signal-to-noise ratio (mean 7.8) were not different between CT acquisitions (p=0.12-0.91). However, the visibility scores of in-stent restenosis were different (p<0.05) between ECG-gated CTA techniques: (a) 140-kV prospective (effective dose 4.6 mSv), 1.6; (b) 120-kV prospective (3.3 mSv), 1.8; (c) 140-kV retrospective (16.4-18.8 mSv), 1.9; and (d) 120-kV retrospective (11.0-13.4 mSv), 1.9. Thus, 140-kV prospective ECG-triggered CTA improves coronary in-stent restenosis visibility at a lower radiation dose compared with retrospective ECG-gated CTA. (orig.)

SU-E-J-214: Comparative Assessment On IGRT On Partial Bladder Cancer Treatment Between CT-On-Rails (CTOR) and KV Cone Beam CT (CBCT)

International Nuclear Information System (INIS)

Lin, T; Ma, C

2014-01-01

Purpose: Image-Guided radiation therapy(IGRT) depends on reliable online patient-specific anatomy information to address random and progressive anatomy changes. Large margins have been suggested to bladder cancer treatment due to large daily bladder anatomy variation. KV Cone beam CT(CBCT) has been used in IGRT localization prevalently; however, its lack of soft tissue contrast makes clinicians hesitate to perform daily soft tissue alignment with CBCT for partial bladder cancer treatment. This study compares the localization uncertainties of bladder cancer IGRT using CTon- Rails(CTOR) and CBCT. Methods: Three T2N0M0 bladder cancer patients (total of 66 Gy to partial bladder alone) were localized daily with either CTOR or CBCT for their entire treatment course. A total of 71 sets of CTOR and 22 sets of CBCT images were acquired and registered with original planning CT scans by radiation therapists and approved by radiation oncologists for the daily treatment. CTOR scanning entailed 2mm slice thickness, 0.98mm axial voxel size, 120kVp and 240mAs. CBCT used a half fan pelvis protocol from Varian OBI system with 2mm slice thickness, 0.98axial voxel size, 125kVp, and 680mAs. Daily localization distribution was compared. Accuracy of CTOR and CBCT on partial bladder alignment was also evaluated by comparing bladder PTV coverage. Results: 1cm all around PTV margins were used in every patient except target superior limit margin to 0mm due to bowel constraint. Daily shifts on CTOR averaged to 0.48, 0.24, 0.19 mms(SI,Lat,AP directions); CBCT averaged to 0.43, 0.09, 0.19 mms(SI,Lat,AP directions). The CTOR daily localization showed superior results of V100% of PTV(102% CTOR vs. 89% CBCT) and bowel(Dmax 69.5Gy vs. 78Gy CBCT). CTOR images showed much higher contrast on bladder PTV alignment. Conclusion: CTOR daily localization for IGRT is more dosimetrically beneficial for partial bladder cancer treatment than kV CBCT localization and provided better soft tissue PTV

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

Science.gov (United States)

2010-03-03

... Rapids 230kV Transmission Project AGENCY: Rural Utilities Service, USDA. ACTION: Notice of Availability... copy of the Draft EIS may be viewed online at the following Web sites: http://www.usda.gov/rus/water..., Longville, MN 56655; Walker Public Library, 207 4th St., Walker, MN 56484; Bovey Public Library--Village...

Structured pathology reporting improves the macroscopic assessment of rectal tumour resection specimens.

Science.gov (United States)

King, Simon; Dimech, Margaret; Johnstone, Susan

2016-06-01

We examined whether introduction of a structured macroscopic reporting template for rectal tumour resection specimens improved the completeness and efficiency in collecting key macroscopic data elements. Fifty free text (narrative) macroscopic reports retrieved from 2012 to 2014 were compared with 50 structured macroscopic reports from 2013 to 2015, all of which were generated at John Hunter Hospital, Newcastle, NSW. The six standard macroscopic data elements examined in this study were reported in all 50 anatomical pathology reports using a structured macroscopic reporting dictation template. Free text reports demonstrated significantly impaired data collection when recording intactness of mesorectum (p<0.001), relationship to anterior peritoneal reflection (p=0.028) and distance of tumour to the non-peritonealised circumferential margin (p<0.001). The number of words used was also significantly (p<0.001) reduced using pre-formatted structured reports compared to free text reports. The introduction of a structured reporting dictation template improves data collection and may reduce the subsequent administrative burden when macroscopically evaluating rectal resections. Copyright © 2016 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

The temperate Burkholderia phage AP3 of the Peduovirinae shows efficient antimicrobial activity against B. cenocepacia of the IIIA lineage.

Science.gov (United States)

Roszniowski, Bartosz; Latka, Agnieszka; Maciejewska, Barbara; Vandenheuvel, Dieter; Olszak, Tomasz; Briers, Yves; Holt, Giles S; Valvano, Miguel A; Lavigne, Rob; Smith, Darren L; Drulis-Kawa, Zuzanna

2017-02-01

Burkholderia phage AP3 (vB_BceM_AP3) is a temperate virus of the Myoviridae and the Peduovirinae subfamily (P2likevirus genus). This phage specifically infects multidrug-resistant clinical Burkholderia cenocepacia lineage IIIA strains commonly isolated from cystic fibrosis patients. AP3 exhibits high pairwise nucleotide identity (61.7 %) to Burkholderia phage KS5, specific to the same B. cenocepacia host, and has 46.7-49.5 % identity to phages infecting other species of Burkholderia. The lysis cassette of these related phages has a similar organization (putative antiholin, putative holin, endolysin, and spanins) and shows 29-98 % homology between specific lysis genes, in contrast to Enterobacteria phage P2, the hallmark phage of this genus. The AP3 and KS5 lysis genes have conserved locations and high amino acid sequence similarity. The AP3 bacteriophage particles remain infective up to 5 h at pH 4-10 and are stable at 60 °C for 30 min, but are sensitive to chloroform, with no remaining infective particles after 24 h of treatment. AP3 lysogeny can occur by stable genomic integration and by pseudo-lysogeny. The lysogenic bacterial mutants did not exhibit any significant changes in virulence compared to wild-type host strain when tested in the Galleria mellonella moth wax model. Moreover, AP3 treatment of larvae infected with B. cenocepacia revealed a significant increase (P < 0.0001) in larvae survival in comparison to AP3-untreated infected larvae. AP3 showed robust lytic activity, as evidenced by its broad host range, the absence of increased virulence in lysogenic isolates, the lack of bacterial gene disruption conditioned by bacterial tRNA downstream integration site, and the absence of detected toxin sequences. These data suggest that the AP3 phage is a promising potent agent against bacteria belonging to the most common B. cenocepacia IIIA lineage strains.

A compact 100 kV high voltage glycol capacitor.

Science.gov (United States)

Wang, Langning; Liu, Jinliang; Feng, Jiahuai

2015-01-01

A high voltage capacitor is described in this paper. The capacitor uses glycerol as energy storage medium, has a large capacitance close to 1 nF, can hold off voltages of up to 100 kV for μs charging time. Allowing for low inductance, the capacitor electrode is designed as coaxial structure, which is different from the common structure of the ceramic capacitor. With a steady capacitance at different frequencies and a high hold-off voltage of up to 100 kV, the glycol capacitor design provides a potential substitute for the ceramic capacitors in pulse-forming network modulator to generate high voltage pulses with a width longer than 100 ns.

Pharmacological dissection of K(v)7.1 channels in systemic and pulmonary arteries

DEFF Research Database (Denmark)

Chadha, Preet S; Zunke, Friederike; Davis, Alison J

2012-01-01

The aim of this study was to characterize the functional impact of KCNQ1-encoded voltage-dependent potassium channels (K(v)7.1) in the vasculature.......The aim of this study was to characterize the functional impact of KCNQ1-encoded voltage-dependent potassium channels (K(v)7.1) in the vasculature....

harmonic load modeling: a case study of 33 kv abuja steel mill feeder

African Journals Online (AJOL)

HOD

techniques are adopted. This paper studied the harmonic orders of the 33 kV Abuja Steel Feeder modeled as a ... (ETAP) software package was deployed to perform Discrete Fast Transform (DFT) while the input ... and documented in research and development articles ... network with 33kV Abuja Steel feeder as case study.

Superconductivity and macroscopic quantum phenomena

International Nuclear Information System (INIS)

Rogovin, D.; Scully, M.

1976-01-01

It is often asserted that superconducting systems are manifestations of quantum mechanics on a macroscopic scale. In this review article it is demonstrated that this quantum assertion is true within the framework of the microscopic theory of superconductivity. (Auth.)

Macroscopic quantum tunnelling in a current biased Josephson junction

International Nuclear Information System (INIS)

Martinis, J.M.; Devoret, M.H.; Clarke, J.; Urbina, C.

1984-11-01

We discuss in this work an attempt to answer experimentally the question: do macroscopic variables obey quantum mechanics. More precisely, this experiment deals with the question of quantum-mechanical tunnelling of a macroscopic variable, a subject related to the famous Schrodinger's cat problem in the theory of measurement

Serum Starvation-Induced Voltage-Gated Potassium Channel Kv7.5 Expression and Its Regulation by Sp1 in Canine Osteosarcoma Cells

Directory of Open Access Journals (Sweden)

Bo Hyung Lee

2014-01-01

Full Text Available The KCNQ gene family, whose members encode Kv7 channels, belongs to the voltage-gated potassium (Kv channel group. The roles of this gene family have been widely investigated in nerve and muscle cells. In the present study, we investigated several characteristics of Kv7.5, which is strongly expressed in the canine osteosarcoma cell line, CCL-183. Serum starvation upregulated Kv7.5 expression, and the Kv7 channel opener, flupirtine, attenuated cell proliferation by arresting cells in the G0/G1 phase. We also showed that Kv7.5 knockdown helps CCL-183 cells to proliferate. In an effort to find an endogenous regulator of Kv7.5, we used mithramycin A to reduce the level of the transcription factor Sp1, and it strongly inhibited the induction of Kv7.5 in CCL-183 cells. These results suggest that the activation of Kv7.5 by flupirtine may exert an anti-proliferative effect in canine osteosarcoma. Therefore, Kv7.5 is a possible molecular target for canine osteosarcoma therapy.

Physically-based modeling of the cyclic macroscopic behaviour of metals

International Nuclear Information System (INIS)

Sauzay, M.; Evrard, P.; Steckmeyer, A.; Ferrie, E.

2010-01-01

Grain size seems to have only a minor influence on the cyclic strain strain curves (CSSCs) of metallic polycrystals of medium to high stacking fault energy (SFE). That is why many authors tried to deduce the macroscopic CSSCs curves from the single crystals ones. Either crystals oriented for single slip or crystals oriented for multiple slip could be considered. In addition, a scale transition law should be used (from the grain scale to the macroscopic scale). Authors generally used either the Sachs rule (homogeneous single slip) or the Taylor one (homogeneous plastic strain, multiple slip). But the predicted macroscopic CSSCs do not generally agree with the experimental data for metals and alloys, presenting various SFE values. In order to avoid the choice of a particular scale transition rule, many finite element (FE) computations have been carried out using meshes of polycrystals including more than one hundred grains without texture. This allows the study of the influence of the crystalline constitutive laws on the macroscopic CSSCs. Activation of a secondary slip system in grains oriented for single slip is either allowed or hindered (slip planarity), which affects strongly the macroscopic CSSCs. The more planar the slip, the higher the predicted macroscopic stress amplitudes. If grains oriented for single slip obey slip planarity and two crystalline CSSCs are used (one for single slip grains and one for multiple slip grains), then the predicted macroscopic CSSCs agree well with experimental data provided the SFE is not too low (316L, copper, nickel, aluminium). Finally, the incremental self-consistent Hill-Hutchinson homogenization model is used for predicting CSS curves and partially validated with respect to the curves computed by the FE method. (authors)

Metallized solid rocket propellants based on AN/AP and PSAN/AP for access to space

Science.gov (United States)

Levi, S.; Signoriello, D.; Gabardi, A.; Molinari, M.; Galfetti, L.; Deluca, L. T.; Cianfanelli, S.; Klyakin, G. F.

2009-09-01

Solid rocket propellants based on dual mixes of inorganic crystalline oxidizers (ammonium nitrate (AN) and ammonium perchlorate (AP)) with binder and a mixture of micrometric-nanometric aluminum were investigated. Ammonium nitrate is a low-cost oxidizer, producing environment friendly combustion products but with lower specific impulse compared to AP. The better performance obtained with AP and the low quantity of toxic emissions obtained by using AN have suggested an interesting compromise based on a dual mixture of the two oxidizers. To improve the thermal response of raw AN, different types of phase stabilized AN (PSAN) and AN/AP co-crystals were investigated.

Evaluation of variation of voltage (kV) absorbed dose in chest CT scans

International Nuclear Information System (INIS)

Mendonca, Bruna G.A.; Mourao, Arnaldo P.

2013-01-01

Computed tomography (CT) is one of the most important diagnostic techniques images today. The increasing utilization of CT implies a significant increase of population exposure to ionizing radiation. Optimization of practice aims to reduce doses to patients because the image quality is directly related to the diagnosis. You can decrease the amount of dose to the patient, and maintain the quality of the image. There are several parameters that can be manipulated in a CT scan and these parameters can be used to reduce the energy deposited in the patient. Based on this, we analyzed the variation of dose deposited in the lungs, breasts and thyroid, by varying the supply voltage of the tube. Scans of the thorax were performed following the protocol of routine chest with constant and variable current for the same applied voltage. Moreover, a female phantom was used and thermoluminescent dosimeters (TLD-100), model bat, were used to record the specific organ doses. Scans were performed on a GE CT scanner, model 64 Discovery channels. Higher doses were recorded for the voltage of 120 kV with 200 mAs in the lungs (22.46 mGy) and thyroid (32.22 mGy). For scans with automatic mAs, variable between 100 and 440, this same tension contributed to the higher doses. The best examination in terms of the dose that was used with automatic 80 kV mAs, whose lungs and thyroid received lower dose. For the best breast exam was 100 kV. Since the increase in the 80 kV to 100 kV no impact so much the dose deposited in the lungs, it can be concluded that lowering the applied voltage to 100 kV resulted in a reduction in the dose absorbed by the patient. These results can contribute to optimizing scans of the chest computed tomography

A Review on Macroscopic Pedestrian Flow Modelling

Directory of Open Access Journals (Sweden)

Anna Kormanová

2013-12-01

Full Text Available This paper reviews several various approaches to macroscopic pedestrian modelling. It describes hydrodynamic models based on similarity of pedestrian flow with fluids and gases; first-order flow models that use fundamental diagrams and conservation equation; and a model similar to LWR vehicular traffic model, which allows non-classical shocks. At the end of the paper there is stated a comparison of described models, intended to find appropriate macroscopic model to eventually be a part of a hybrid model. The future work of the author is outlined.

AP1000. The PWR revisited

International Nuclear Information System (INIS)

Gaio, P.

2006-01-01

The distinguishing features of Westinghouse's AP1000 advanced passive pressurized water reactor are highlighted. In particular, the AP1000's passive safety features are described as well as their implications for simplifying the design, construction, and operation of this design compared to currently operating plants, and significantly increasing safety margins over current plants as well. The AP1000 design specifically incorporates the knowledge acquired from the substantial accumulation of power reactor operating experience and benefits from the application of the Probabilistic Risk Assessment in the design process itself. The AP1000 design has been certified by the US Nuclear Regulatory Commission under its new rules for licensing new nuclear plants, 10 CFR Part 52, and is the subject of six combined Construction and Operating License applications now being developed. Currently the AP1000 design is being assessed against the EUR Rev C requirements for new nuclear power plants in Europe. (author)

AP statistics crash course

CERN Document Server

D'Alessio, Michael

2012-01-01

AP Statistics Crash Course - Gets You a Higher Advanced Placement Score in Less Time Crash Course is perfect for the time-crunched student, the last-minute studier, or anyone who wants a refresher on the subject. AP Statistics Crash Course gives you: Targeted, Focused Review - Study Only What You Need to Know Crash Course is based on an in-depth analysis of the AP Statistics course description outline and actual Advanced Placement test questions. It covers only the information tested on the exam, so you can make the most of your valuable study time. Our easy-to-read format covers: exploring da

Microscopic to macroscopic depletion model development for FORMOSA-P

International Nuclear Information System (INIS)

Noh, J.M.; Turinsky, P.J.; Sarsour, H.N.

1996-01-01

Microscopic depletion has been gaining popularity with regard to employment in reactor core nodal calculations, mainly attributed to the superiority of microscopic depletion in treating spectral history effects during depletion. Another trend is the employment of loading pattern optimization computer codes in support of reload core design. Use of such optimization codes has significantly reduced design efforts to optimize reload core loading patterns associated with increasingly complicated lattice designs. A microscopic depletion model has been developed for the FORMOSA-P pressurized water reactor (PWR) loading pattern optimization code. This was done for both fidelity improvements and to make FORMOSA-P compatible with microscopic-based nuclear design methods. Needless to say, microscopic depletion requires more computational effort compared with macroscopic depletion. This implies that microscopic depletion may be computationally restrictive if employed during the loading pattern optimization calculation because many loading patterns are examined during the course of an optimization search. Therefore, the microscopic depletion model developed here uses combined models of microscopic and macroscopic depletion. This is done by first performing microscopic depletions for a subset of possible loading patterns from which 'collapsed' macroscopic cross sections are obtained. The collapsed macroscopic cross sections inherently incorporate spectral history effects. Subsequently, the optimization calculations are done using the collapsed macroscopic cross sections. Using this approach allows maintenance of microscopic depletion level accuracy without substantial additional computing resources

Active Polar Two-Fluid Macroscopic Dynamics

Science.gov (United States)

Pleiner, Harald; Svensek, Daniel; Brand, Helmut R.

2014-03-01

We study the dynamics of systems with a polar dynamic preferred direction. Examples include the pattern-forming growth of bacteria (in a solvent, shoals of fish (moving in water currents), flocks of birds and migrating insects (flying in windy air). Because the preferred direction only exists dynamically, but not statically, the macroscopic variable of choice is the macroscopic velocity associated with the motion of the active units. We derive the macroscopic equations for such a system and discuss novel static, reversible and irreversible cross-couplings connected to this second velocity. We find a normal mode structure quite different compared to the static descriptions, as well as linear couplings between (active) flow and e.g. densities and concentrations due to the genuine two-fluid transport derivatives. On the other hand, we get, quite similar to the static case, a direct linear relation between the stress tensor and the structure tensor. This prominent ``active'' term is responsible for many active effects, meaning that our approach can describe those effects as well. In addition, we also deal with explicitly chiral systems, which are important for many active systems. In particular, we find an active flow-induced heat current specific for the dynamic chiral polar order.

Macroscopic Hematuria After Conventional or Hypofractionated Radiation Therapy: Results From a Prospective Phase 3 Study

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Sanguineti, Giuseppe, E-mail: sanguineti@ifo.it [Department of Radiation Oncology, Regina Elena National Cancer Institute, Rome (Italy); Arcidiacono, Fabio [Department of Radiation Oncology, Regina Elena National Cancer Institute, Rome (Italy); Landoni, Valeria [Department of Physics, Regina Elena National Cancer Institute, Rome (Italy); Saracino, Bianca Maria; Farneti, Alessia; Arcangeli, Stefano; Petrongari, Maria Grazia; Gomellini, Sara [Department of Radiation Oncology, Regina Elena National Cancer Institute, Rome (Italy); Strigari, Lidia [Department of Physics, Regina Elena National Cancer Institute, Rome (Italy); Arcangeli, Giorgio [Department of Radiation Oncology, Regina Elena National Cancer Institute, Rome (Italy)

2016-10-01

Purpose: To assess the macroscopic hematuria rates within a single-institution randomized phase 3 trial comparing dose-escalated, conventionally fractionated radiation therapy (CFRT) and moderately hypofractionated radiation therapy (MHRT) for localized prostate cancer. Methods and Materials: Patients with intermediate- to high-risk localized prostate cancer were treated with conformal RT and short-course androgen deprivation. Both the prostate and the entire seminal vesicles were treated to 80 Gy in 40 fractions over 8 weeks (CFRT) or 62 Gy in 20 fractions over 5 weeks (MHRT). The endpoint of the present study was the development of any episode or grade of macroscopic hematuria. The median follow-up period was 93 months (range 6-143). Results: Macroscopic hematuria was reported by 25 of 168 patients (14.9%). The actuarial estimate of hematuria at 8 years was 17.0% (95% confidence interval [CI] 10.7%-23.3%). The number of patients with hematuria was 6 and 19 in the CFRT and MHRT arms, respectively, for an actuarial 8-year estimate of 9.7% and 24.3%, respectively (hazard ratio 3.468, 95% CI 1.385-8.684; P=.008). Overall, 8 of 25 patients were found to have biopsy-proven urothelial carcinoma (3 in the CFRT arm and 5 in the MHRT arm; P=.27). Thus, the 8-year actuarial incidence of macroscopic hematuria (after censoring urothelial cancer–related episodes) was 4.1% and 18.2% after CFRT and MHRT, respectively (hazard ratio 4.961, 95% CI 1.426-17.263; P=.012). The results were confirmed by multivariate analysis after accounting for several patient-, treatment-, and tumor-related covariates. Conclusions: MHRT was associated with a statistically significant increased risk of macroscopic hematuria compared with CFRT.

Macroscopic Hematuria After Conventional or Hypofractionated Radiation Therapy: Results From a Prospective Phase 3 Study

International Nuclear Information System (INIS)

Sanguineti, Giuseppe; Arcidiacono, Fabio; Landoni, Valeria; Saracino, Bianca Maria; Farneti, Alessia; Arcangeli, Stefano; Petrongari, Maria Grazia; Gomellini, Sara; Strigari, Lidia; Arcangeli, Giorgio

2016-01-01

Purpose: To assess the macroscopic hematuria rates within a single-institution randomized phase 3 trial comparing dose-escalated, conventionally fractionated radiation therapy (CFRT) and moderately hypofractionated radiation therapy (MHRT) for localized prostate cancer. Methods and Materials: Patients with intermediate- to high-risk localized prostate cancer were treated with conformal RT and short-course androgen deprivation. Both the prostate and the entire seminal vesicles were treated to 80 Gy in 40 fractions over 8 weeks (CFRT) or 62 Gy in 20 fractions over 5 weeks (MHRT). The endpoint of the present study was the development of any episode or grade of macroscopic hematuria. The median follow-up period was 93 months (range 6-143). Results: Macroscopic hematuria was reported by 25 of 168 patients (14.9%). The actuarial estimate of hematuria at 8 years was 17.0% (95% confidence interval [CI] 10.7%-23.3%). The number of patients with hematuria was 6 and 19 in the CFRT and MHRT arms, respectively, for an actuarial 8-year estimate of 9.7% and 24.3%, respectively (hazard ratio 3.468, 95% CI 1.385-8.684; P=.008). Overall, 8 of 25 patients were found to have biopsy-proven urothelial carcinoma (3 in the CFRT arm and 5 in the MHRT arm; P=.27). Thus, the 8-year actuarial incidence of macroscopic hematuria (after censoring urothelial cancer–related episodes) was 4.1% and 18.2% after CFRT and MHRT, respectively (hazard ratio 4.961, 95% CI 1.426-17.263; P=.012). The results were confirmed by multivariate analysis after accounting for several patient-, treatment-, and tumor-related covariates. Conclusions: MHRT was associated with a statistically significant increased risk of macroscopic hematuria compared with CFRT.

Voltage Analysis Improvement of 150 kV Transmission Subsystem Using Static Synchronous Compensator (STATCOM)