Computation and analysis of backward ray-tracing in aero-optics flow fields.

PubMed

Xu, Liang; Xue, Deting; Lv, Xiaoyi

2018-01-08

A backward ray-tracing method is proposed for aero-optics simulation. Different from forward tracing, the backward tracing direction is from the internal sensor to the distant target. Along this direction, the tracing in turn goes through the internal gas region, the aero-optics flow field, and the freestream. The coordinate value, the density, and the refractive index are calculated at each tracing step. A stopping criterion is developed to ensure the tracing stops at the outer edge of the aero-optics flow field. As a demonstration, the analysis is carried out for a typical blunt nosed vehicle. The backward tracing method and stopping criterion greatly simplify the ray-tracing computations in the aero-optics flow field, and they can be extended to our active laser illumination aero-optics study because of the reciprocity principle.

Automated and Cooperative Vehicle Merging at Highway On-Ramps

DOE PAGES

Rios-Torres, Jackeline; Malikopoulos, Andreas A.

2016-08-05

Recognition of necessities of connected and automated vehicles (CAVs) is gaining momentum. CAVs can improve both transportation network efficiency and safety through control algorithms that can harmonically use all existing information to coordinate the vehicles. This paper addresses the problem of optimally coordinating CAVs at merging roadways to achieve smooth traffic flow without stop-and-go driving. Here we present an optimization framework and an analytical closed-form solution that allows online coordination of vehicles at merging zones. The effectiveness of the efficiency of the proposed solution is validated through a simulation, and it is shown that coordination of vehicles can significantly reducemore » both fuel consumption and travel time.« less

Expression-associated polymorphisms of CAV1-CAV2 affect intraocular pressure and high-tension glaucoma risk

PubMed Central

Kim, Sewon; Kim, Kyunglan; Heo, Dong Won; Kim, Jong-Sung; Park, Chan Kee; Kim, Chang-sik

2015-01-01

Purpose The human CAV1-CAV2 locus has been associated with susceptibility to primary open-angle glaucoma in four studies of Caucasian, Chinese, and Pakistani populations, although not in several other studies of non-Korean populations. In this study with Korean participants, the CAV1-CAV2 locus was investigated for associations with susceptibility to primary open-angle glaucoma accompanied by elevated intraocular pressure (IOP), namely, high-tension glaucoma (HTG), as well as with IOP elevation, which is a strong risk factor for glaucoma. Methods Two single nucleotide polymorphisms (SNPs) were genotyped in 1,161 Korean participants including 229 patients with HTG and 932 healthy controls and statistically examined for association with HTG susceptibility and IOP. One SNP was rs4236601 G>A, which had been reported in the original study, and the other SNP was rs17588172 T>G, which was perfectly correlated (r2=1) with another reported SNP rs1052990. Expression quantitative trait loci (eQTL) analysis was performed using GENe Expression VARiation (Genevar) data. Results Both SNPs were associated with HTG susceptibility, but the rs4236601 association disappeared when adjusted for the rs17588172 genotype and not vice versa. The minor allele G of rs17588172 was associated significantly with 1.5-fold increased susceptibility to HTG (p=0.0069) and marginally with IOP elevation (p=0.043) versus the major allele T. This minor allele was also associated with decreased CAV1 and CAV2 mRNA in skin and adipose according to the Genevar eQTL analysis. Conclusions The minor allele G of rs17588172 in the CAV1-CAV2 locus is associated with decreased expression of CAV1 and CAV2 in some tissues, marginally with IOP elevation, and consequently with increased susceptibility to HTG. PMID:26015768

Aero/structural tailoring of engine blades (AERO/STAEBL)

NASA Technical Reports Server (NTRS)

Brown, K. W.

1988-01-01

This report describes the Aero/Structural Tailoring of Engine Blades (AERO/STAEBL) program, which is a computer code used to perform engine fan and compressor blade aero/structural numerical optimizations. These optimizations seek a blade design of minimum operating cost that satisfies realistic blade design constraints. This report documents the overall program (i.e., input, optimization procedures, approximate analyses) and also provides a detailed description of the validation test cases.

Cav1.2 and Cav1.3 L‐type calcium channels independently control short‐ and long‐term sensitization to pain

PubMed Central

Radwani, Houda; Lopez‐Gonzalez, Maria José; Cattaert, Daniel; Roca‐Lapirot, Olivier; Dobremez, Eric; Bouali‐Benazzouz, Rabia; Eiríksdóttir, Emelía; Langel, Ülo; Favereaux, Alexandre; Errami, Mohammed; Landry, Marc

2016-01-01

Key points L‐type calcium channels in the CNS exist as two subunit forming channels, Cav1.2 and Cav1.3, which are involved in short‐ and long‐term plasticity.We demonstrate that Cav1.3 but not Cav1.2 is essential for wind‐up.These results identify Cav1.3 as a key conductance responsible for short‐term sensitization in physiological pain transmission.We confirm the role of Cav1.2 in a model of long‐term plasticity associated with neuropathic pain.Up‐regulation of Cav1.2 and down‐regultation of Cav1.3 in neuropathic pain underlies the switch from physiology to pathology.Finally, the results of the present study reveal that therapeutic targeting molecular pathways involved in wind‐up may be not relevant in the treatment of neuropathy. Abstract Short‐term central sensitization to pain temporarily increases the responsiveness of nociceptive pathways after peripheral injury. In dorsal horn neurons (DHNs), short‐term sensitization can be monitored through the study of wind‐up. Wind‐up, a progressive increase in DHNs response following repetitive peripheral stimulations, depends on the post‐synaptic L‐type calcium channels. In the dorsal horn of the spinal cord, two L‐type calcium channels are present, Cav1.2 and Cav1.3, each displaying specific kinetics and spatial distribution. In the present study, we used a mathematical model of DHNs in which we integrated the specific patterns of expression of each Cav subunits. This mathematical approach reveals that Cav1.3 is necessary for the onset of wind‐up, whereas Cav1.2 is not and that synaptically triggered wind‐up requires NMDA receptor activation. We then switched to a biological preparation in which we knocked down Cav subunits and confirmed the prominent role of Cav1.3 in both naive and spinal nerve ligation model of neuropathy (SNL). Interestingly, although a clear mechanical allodynia dependent on Cav1.2 expression was observed after SNL, the amplitude of wind‐up was decreased

High-Temperature Adhesives for Thermally Stable Aero-Assist Technologies

NASA Technical Reports Server (NTRS)

Eberts, Kenneth; Ou, Runqing

2013-01-01

Aero-assist technologies are used to control the velocity of exploration vehicles (EVs) when entering Earth or other planetary atmospheres. Since entry of EVs in planetary atmospheres results in significant heating, thermally stable aero-assist technologies are required to avoid the high heating rates while maintaining low mass. Polymer adhesives are used in aero-assist structures because of the need for high flexibility and good bonding between layers of polymer films or fabrics. However, current polymer adhesives cannot withstand temperatures above 400 C. This innovation utilizes nanotechnology capabilities to address this need, leading to the development of high-temperature adhesives that exhibit high thermal conductivity in addition to increased thermal decomposition temperature. Enhanced thermal conductivity will help to dissipate heat quickly and effectively to avoid temperature rising to harmful levels. This, together with increased thermal decomposition temperature, will enable the adhesives to sustain transient high-temperature conditions.

Differential Cav2.1 and Cav2.3 channel inhibition by baclofen and α-conotoxin Vc1.1 via GABAB receptor activation

PubMed Central

McArthur, Jeffrey R.; Cuny, Hartmut; Clark, Richard J.; Adams, David J.

2014-01-01

Neuronal Cav2.1 (P/Q-type), Cav2.2 (N-type), and Cav2.3 (R-type) calcium channels contribute to synaptic transmission and are modulated through G protein–coupled receptor pathways. The analgesic α-conotoxin Vc1.1 acts through γ-aminobutyric acid type B (GABAB) receptors (GABABRs) to inhibit Cav2.2 channels. We investigated GABABR-mediated modulation by Vc1.1, a cyclized form of Vc1.1 (c-Vc1.1), and the GABABR agonist baclofen of human Cav2.1 or Cav2.3 channels heterologously expressed in human embryonic kidney cells. 50 µM baclofen inhibited Cav2.1 and Cav2.3 channel Ba2+ currents by ∼40%, whereas c-Vc1.1 did not affect Cav2.1 but potently inhibited Cav2.3, with a half-maximal inhibitory concentration of ∼300 pM. Depolarizing paired pulses revealed that ∼75% of the baclofen inhibition of Cav2.1 was voltage dependent and could be relieved by strong depolarization. In contrast, baclofen or Vc1.1 inhibition of Cav2.3 channels was solely mediated through voltage-independent pathways that could be disrupted by pertussis toxin, guanosine 5′-[β-thio]diphosphate trilithium salt, or the GABABR antagonist CGP55845. Overexpression of the kinase c-Src significantly increased inhibition of Cav2.3 by c-Vc1.1. Conversely, coexpression of a catalytically inactive double mutant form of c-Src or pretreatment with a phosphorylated pp60c-Src peptide abolished the effect of c-Vc1.1. Site-directed mutational analyses of Cav2.3 demonstrated that tyrosines 1761 and 1765 within exon 37 are critical for inhibition of Cav2.3 by c-Vc1.1 and are involved in baclofen inhibition of these channels. Remarkably, point mutations introducing specific c-Src phosphorylation sites into human Cav2.1 channels conferred c-Vc1.1 sensitivity. Our findings show that Vc1.1 inhibition of Cav2.3, which defines Cav2.3 channels as potential targets for analgesic α-conotoxins, is caused by specific c-Src phosphorylation sites in the C terminus. PMID:24688019

Immunity to canine adenovirus respiratory disease: a comparison of attenuated CAV-1 and CAV-2 vaccines.

PubMed

Cornwell, H J; Koptopoulos, G; Thompson, H; McCandlish, I A; Wright, N G

1982-01-09

Four litters of puppies were divided into three groups. One group was vaccinated with a live CAV-1 vaccine and another with a live CAV-2 vaccine. Throat swabs were collected from two dogs in each of these groups to monitor the possible excretion of vaccine virus, but none was found. Both groups, together with the third group of unvaccinated controls, were challenged 17 days later with an aerosol of virulent CAV-2. One dog from each group was killed on the third, fourth, seventh, ninth, 11th and 14th days after challenge. The unvaccinated dogs developed a clinical disease characterised by anorexia, dullness, coughing and tachypnoea. The lungs were consolidated and histological examination revealed the main lesion to be a severe necrotising bronchiolitis. Large amounts of virus were present in the respiratory tissues of these dogs and high titres of virus were isolated from throat swabs. In contrast, both groups of vaccinated dogs remained clinically almost normal with minimal lesions, present for a much shorter period of time. Virus was found on day 4 in the respiratory tissues of one dog vaccinated with CAV-1 but the other vaccinated animals contained little or no virus. In general, the degree of protection afforded by CAV-1 vaccine seemed similar to that provided by CAV-2 vaccine.

Suppression of Sleep Spindle Rhythmogenesis in Mice with Deletion of CaV3.2 and CaV3.3 T-type Ca2+ Channels

PubMed Central

Pellegrini, Chiara; Lecci, Sandro; Lüthi, Anita; Astori, Simone

2016-01-01

Study Objectives: Low-threshold voltage-gated T-type Ca2+ channels (T-channels or CaV3 channels) sustain oscillatory discharges of thalamocortical (TC) and nucleus Reticularis thalami (nRt) cells. The CaV3.3 subtype dominates nRt rhythmic bursting and mediates a substantial fraction of spindle power in the NREM sleep EEG. CaV3.2 channels are also found in nRt, but whether these contribute to nRt-dependent spindle generation is unexplored. We investigated thalamic rhythmogenesis in mice lacking this subtype in isolation (CaV3.2KO mice) or in concomitance with CaV3.3 deletion (CaV3.double-knockout (DKO) mice). Methods: We examined discharge characteristics of thalamic cells and intrathalamic evoked synaptic transmission in brain slices from wild-type, CaV3.2KO and CaV3.DKO mice through patch-clamp recordings. The sleep profile of freely behaving CaV3.2KO and CaV3.DKO mice was assessed by polysomnographic recordings. Results: CaV3.2 channel deficiency left nRt discharge properties largely unaltered, but additional deletion of CaV3.3 channels fully abolished low-threshold whole-cell Ca2+ currents and bursting, and suppressed burst-mediated inhibitory responses in TC cells. CaV3.DKO mice had more fragmented sleep, with shorter NREM sleep episodes and more frequent microarousals. The NREM sleep EEG power spectrum displayed a relative suppression of the σ frequency band (10–15 Hz), which was accompanied by an increase in the δ band (1–4 Hz). Conclusions: Consistent with previous findings, CaV3.3 channels dominate nRt rhythmogenesis, but the lack of CaV3.2 channels further aggravates neuronal, synaptic, and EEG deficits. Therefore, CaV3.2 channels can boost intrathalamic synaptic transmission, and might play a modulatory role adjusting the relative presence of NREM sleep EEG rhythms. Citation: Pellegrini C, Lecci S, Lüthi A, Astori S. Suppression of sleep spindle rhythmogenesis in mice with deletion of Cav3.2 and Cav3.3 T-type Ca2+ channels. SLEEP 2016;39(4):875�

Basic Simulation Environment for Highly Customized Connected and Autonomous Vehicle Kinematic Scenarios.

PubMed

Chai, Linguo; Cai, Baigen; ShangGuan, Wei; Wang, Jian; Wang, Huashen

2017-08-23

To enhance the reality of Connected and Autonomous Vehicles (CAVs) kinematic simulation scenarios and to guarantee the accuracy and reliability of the verification, a four-layer CAVs kinematic simulation framework, which is composed with road network layer, vehicle operating layer, uncertainties modelling layer and demonstrating layer, is proposed in this paper. Properties of the intersections are defined to describe the road network. A target position based vehicle position updating method is designed to simulate such vehicle behaviors as lane changing and turning. Vehicle kinematic models are implemented to maintain the status of the vehicles when they are moving towards the target position. Priorities for individual vehicle control are authorized for different layers. Operation mechanisms of CAVs uncertainties, which are defined as position error and communication delay in this paper, are implemented in the simulation to enhance the reality of the simulation. A simulation platform is developed based on the proposed methodology. A comparison of simulated and theoretical vehicle delay has been analyzed to prove the validity and the creditability of the platform. The scenario of rear-end collision avoidance is conducted to verify the uncertainties operating mechanisms, and a slot-based intersections (SIs) control strategy is realized and verified in the simulation platform to show the supports of the platform to CAVs kinematic simulation and verification.

Basic Simulation Environment for Highly Customized Connected and Autonomous Vehicle Kinematic Scenarios

PubMed Central

Chai, Linguo; Cai, Baigen; ShangGuan, Wei; Wang, Jian; Wang, Huashen

2017-01-01

To enhance the reality of Connected and Autonomous Vehicles (CAVs) kinematic simulation scenarios and to guarantee the accuracy and reliability of the verification, a four-layer CAVs kinematic simulation framework, which is composed with road network layer, vehicle operating layer, uncertainties modelling layer and demonstrating layer, is proposed in this paper. Properties of the intersections are defined to describe the road network. A target position based vehicle position updating method is designed to simulate such vehicle behaviors as lane changing and turning. Vehicle kinematic models are implemented to maintain the status of the vehicles when they are moving towards the target position. Priorities for individual vehicle control are authorized for different layers. Operation mechanisms of CAVs uncertainties, which are defined as position error and communication delay in this paper, are implemented in the simulation to enhance the reality of the simulation. A simulation platform is developed based on the proposed methodology. A comparison of simulated and theoretical vehicle delay has been analyzed to prove the validity and the creditability of the platform. The scenario of rear-end collision avoidance is conducted to verify the uncertainties operating mechanisms, and a slot-based intersections (SIs) control strategy is realized and verified in the simulation platform to show the supports of the platform to CAVs kinematic simulation and verification. PMID:28832518

Cav-1 promotes atherosclerosis by activating JNK-associated signaling.

PubMed

Wang, Dong-Xia; Pan, Yong-Quan; Liu, Bing; Dai, Li

2018-05-07

The objective of the study is to calculate the role and underlying the molecular mechanisms of caveolin-1 (Cav-1) in atherosclerosis (AS). Cav-1 was mainly expressed in the endothelial cells of atherosclerotic lesions in both human patients and apolipoprotein E deficient (ApoE -/- ) mice. Cav-1 deficiency (Cav-1 -/- ) attenuated high-fat diet (HFD)-induced atherosclerotic lesions in ApoE -/- mice, supported by the reduced aortic plaques. Cav-1 -/- reduced the macrophage content and decreased the release of inflammation-related cytokines or chemokine in serum or abdominal aortas, accompanied with the inactivation of inhibitor κB kinase κ (IKKβ)/p65/IκBα signaling pathway. Also, the activity of mitogen-activated protein kinases 7/c-Jun-N-terminal kinase (MKK7/JNK) signaling was decreased by Cav-1 -/- . In addition, oxidative stress induced by HFD in ApoE -/- mice was alleviated by Cav-1 -/- . In response to HFD, Cav-1 -/- markedly reduced triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDLC) and very low-density lipoprotein-cholesterol (VLDLC) in serum of HFD-fed ApoE -/- mice, whereas enhanced high-density lipoprotein-cholesterol (HDLC) contents. Consistent with these findings, haematoxylin and eosin (H&E) and Oil Red O staining showed fewer lipid droplets in the liver of Cav-1-deficient mice. Further, real time-quantitative PCR (RT-qPCR) analysis indicated that Cav-1 -/- alleviated dyslipidemia both in liver and abdominal aortas of ApoE -/- mice fed with HFD. Cav-1 inhibition-induced attenuation of inflammatory response, oxidative stress and dyslipidemia were confirmed in vitro using mouse vascular smooth muscle cells (VSMCs) treated with ox-LDL. Surprisingly, the processes regulated by Cav-1-knockdown could be abolished through promoting JNK activation in ox-LDL-treated VSMCs. In conclusion, Cav-1 expression could promote HFD-induced AS in a JNK-dependent manner. Copyright © 2018. Published by Elsevier Inc.

Suppression of Sleep Spindle Rhythmogenesis in Mice with Deletion of CaV3.2 and CaV3.3 T-type Ca(2+) Channels.

PubMed

Pellegrini, Chiara; Lecci, Sandro; Lüthi, Anita; Astori, Simone

2016-04-01

Low-threshold voltage-gated T-type Ca(2+) channels (T-channels or CaV3 channels) sustain oscillatory discharges of thalamocortical (TC) and nucleus Reticularis thalami (nRt) cells. The CaV3.3 subtype dominates nRt rhythmic bursting and mediates a substantial fraction of spindle power in the NREM sleep EEG. CaV3.2 channels are also found in nRt, but whether these contribute to nRt-dependent spindle generation is unexplored. We investigated thalamic rhythmogenesis in mice lacking this subtype in isolation (CaV3.2KO mice) or in concomitance with CaV3.3 deletion (CaV3.double-knockout (DKO) mice). We examined discharge characteristics of thalamic cells and intrathalamic evoked synaptic transmission in brain slices from wild-type, CaV3.2KO and CaV3.DKO mice through patch-clamp recordings. The sleep profile of freely behaving CaV3.2KO and CaV3.DKO mice was assessed by polysomnographic recordings. CaV3.2 channel deficiency left nRt discharge properties largely unaltered, but additional deletion of CaV3.3 channels fully abolished low-threshold whole-cell Ca(2+) currents and bursting, and suppressed burst-mediated inhibitory responses in TC cells. CaV3.DKO mice had more fragmented sleep, with shorter NREM sleep episodes and more frequent microarousals. The NREM sleep EEG power spectrum displayed a relative suppression of the σ frequency band (10-15 Hz), which was accompanied by an increase in the δ band (1-4 Hz). Consistent with previous findings, CaV3.3 channels dominate nRt rhythmogenesis, but the lack of CaV3.2 channels further aggravates neuronal, synaptic, and EEG deficits. Therefore, CaV3.2 channels can boost intrathalamic synaptic transmission, and might play a modulatory role adjusting the relative presence of NREM sleep EEG rhythms. © 2016 Associated Professional Sleep Societies, LLC.

Advanced Aero-Propulsive Mid-Lift-to-Drag Ratio Entry Vehicle for Future Exploration Missions

NASA Technical Reports Server (NTRS)

Campbell, C. H.; Stosaric, R. R; Cerimele, C. J.; Wong, K. A.; Valle, G. D.; Garcia, J. A.; Melton, J. E.; Munk, M. M.; Blades, E.; Kuruvila, G.;

Analysis of the Effects of Connected–Automated Vehicle Technologies on Travel Demand

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

Auld, Joshua; Sokolov, Vadim; Stephens, Thomas S.

Connected–automated vehicle (CAV) technologies are likely to have significant effects not only on how vehicles operate in the transportation system, but also on how individuals behave and use their vehicles. While many CAV technologies—such as connected adaptive cruise control and ecosignals—have the potential to increase network throughput and efficiency, many of these same technologies have a secondary effect of reducing driver burden, which can drive changes in travel behavior. Such changes in travel behavior—in effect, lowering the cost of driving—have the potential to increase greatly the utilization of the transportation system with concurrent negative externalities, such as congestion, energy use,more » and emissions, working against the positive effects on the transportation system resulting from increased capacity. To date, few studies have analyzed the potential effects on CAV technologies from a systems perspective; studies often focus on gains and losses to an individual vehicle, at a single intersection, or along a corridor. However, travel demand and traffic flow constitute a complex, adaptive, nonlinear system. Therefore, in this study, an advanced transportation systems simulation model—POLARIS—was used. POLARIS includes cosimulation of travel behavior and traffic flow to study the potential effects of several CAV technologies at the regional level. Various technology penetration levels and changes in travel time sensitivity have been analyzed to determine a potential range of effects on vehicle miles traveled from various CAV technologies.« less

Aerosciences, Aero-Propulsion and Flight Mechanics Technology Development for NASA's Next Generation Launch Technology Program

NASA Technical Reports Server (NTRS)

Cockrell, Charles E., Jr.

2003-01-01

The Next Generation Launch Technology (NGLT) program, Vehicle Systems Research and Technology (VSR&T) project is pursuing technology advancements in aerothermodynamics, aeropropulsion and flight mechanics to enable development of future reusable launch vehicle (RLV) systems. The current design trade space includes rocket-propelled, hypersonic airbreathing and hybrid systems in two-stage and single-stage configurations. Aerothermodynamics technologies include experimental and computational databases to evaluate stage separation of two-stage vehicles as well as computational and trajectory simulation tools for this problem. Additionally, advancements in high-fidelity computational tools and measurement techniques are being pursued along with the study of flow physics phenomena, such as boundary-layer transition. Aero-propulsion technology development includes scramjet flowpath development and integration, with a current emphasis on hypervelocity (Mach 10 and above) operation, as well as the study of aero-propulsive interactions and the impact on overall vehicle performance. Flight mechanics technology development is focused on advanced guidance, navigation and control (GN&C) algorithms and adaptive flight control systems for both rocket-propelled and airbreathing vehicles.

Effects of S(+)-efonidipine on the rabbit sinus node action potential and calcium channel subunits Ca(V)1.2, Ca(V)1.3 and Ca(V)3.1.

PubMed

Tanaka, Hikaru; Namekata, Iyuki; Ogawa, Toru; Tsuneoka, Yayoi; Komikado, Chisa; Takahara, Akira; Iida-Tanaka, Naoko; Izumi-Nakaseko, Hiroko; Tsuru, Hiromichi; Adachi-Akahane, Satomi

2010-12-15

The effect of S(+)-efonidipine on sinus node action potential and calcium channel α-subunits was examined. The slope of the phase 4 depolarization of isolated rabbit sinus node tissue was significantly reduced by S(+)-efonidipine (1 μM), slightly reduced by nifedipine (1 μM), but was not affected by R(-)-efonidipine. S(+)-efonidipine (1 μM), inhibited the expressed Ca(V)1.2, Ca(V)1.3 and Ca(V)3.1 channel currents by 75.7%, 75.3% and 94.0%, nifedipine 84.0%, 43.2% and 14.9%, and R(-)-efonidipine 30.0%, 19.6% and 92.8%, respectively. Thus, the prolongation of the phase 4 depolarization of the rabbit sinus node by S(+)-efonidipine may be explained by blockade of the Ca(V)1.3 channel current. Copyright © 2010 Elsevier B.V. All rights reserved.

Turbofan Volume Dynamics Model for Investigations of Aero-Propulso-Servo-Elastic Effects in a Supersonic Commercial Transport

NASA Technical Reports Server (NTRS)

Connolly, Joseph W.; Kopasakis, George; Lemon, Kimberly A.

2010-01-01

A turbofan simulation has been developed for use in aero-propulso-servo-elastic coupling studies, on supersonic vehicles. A one-dimensional lumped volume approach is used whereby each component (fan, high-pressure compressor, combustor, etc.) is represented as a single volume using characteristic performance maps and conservation equations for continuity, momentum and energy. The simulation is developed in the MATLAB/SIMULINK (The MathWorks, Inc.) environment in order to facilitate controls development, and ease of integration with a future aero-servo-elastic vehicle model being developed at NASA Langley. The complete simulation demonstrated steady state results that closely match a proposed engine suitable for a supersonic business jet at the cruise condition. Preliminary investigation of the transient simulation revealed expected trends for fuel flow disturbances as well as upstream pressure disturbances. A framework for system identification enables development of linear models for controller design. Utilizing this framework, a transfer function modeling an upstream pressure disturbance s impacts on the engine speed is developed as an illustrative case of the system identification. This work will eventually enable an overall vehicle aero-propulso-servo-elastic model

Alcohol Withdrawal-Induced Seizure Susceptibility is Associated with an Upregulation of CaV1.3 Channels in the Rat Inferior Colliculus

PubMed Central

Akinfiresoye, Luli R.; Allard, Joanne S.; Lovinger, David M.

2015-01-01

Background: We previously reported increased current density through L-type voltage-gated Ca2+ (CaV1) channels in inferior colliculus (IC) neurons during alcohol withdrawal. However, the molecular correlate of this increased CaV1 current is currently unknown. Methods: Rats received three daily doses of ethanol every 8 hours for 4 consecutive days; control rats received vehicle. The IC was dissected at various time intervals following alcohol withdrawal, and the mRNA and protein levels of the CaV1.3 and CaV1.2 α1 subunits were measured. In separate experiments, rats were tested for their susceptibility to alcohol withdrawal–induced seizures (AWS) 3, 24, and 48 hours after alcohol withdrawal. Results: In the alcohol-treated group, AWS were observed 24 hours after withdrawal; no seizures were observed at 3 or 48 hours. No seizures were observed at any time in the control-treated rats. Compared to control-treated rats, the mRNA level of the CaV1.3 α1 subunit was increased 1.4-fold, 1.9-fold, and 1.3-fold at 3, 24, and 48 hours, respectively. In contrast, the mRNA level of the CaV1.2 α1 subunit increased 1.5-fold and 1.4-fold at 24 and 48 hours, respectively. At 24 hours, Western blot analyses revealed that the levels of the CaV1.3 and CaV1.2 α1 subunits increased by 52% and 32%, respectively, 24 hours after alcohol withdrawal. In contrast, the CaV1.2 and CaV1.3 α1 subunits were not altered at either 3 or 48 hours during alcohol withdrawal. Conclusions: Expression of the CaV1.3 α1 subunit increased in parallel with AWS development, suggesting that altered L-type CaV1.3 channel expression is an important feature of AWS pathogenesis. PMID:25556199

Constitutive and ghrelin-dependent GHSR1a activation impairs CaV2.1 and CaV2.2 currents in hypothalamic neurons

PubMed Central

López Soto, Eduardo Javier; Agosti, Francina; Cabral, Agustina; Mustafa, Emilio Roman; Damonte, Valentina Martínez; Gandini, Maria Alejandra; Rodríguez, Silvia; Castrogiovanni, Daniel; Felix, Ricardo; Perelló, Mario

2015-01-01

The growth hormone secretagogue receptor type 1a (GHSR1a) has the highest known constitutive activity of any G protein–coupled receptor (GPCR). GHSR1a mediates the action of the hormone ghrelin, and its activation increases transcriptional and electrical activity in hypothalamic neurons. Although GHSR1a is present at GABAergic presynaptic terminals, its effect on neurotransmitter release remains unclear. The activities of the voltage-gated calcium channels, CaV2.1 and CaV2.2, which mediate neurotransmitter release at presynaptic terminals, are modulated by many GPCRs. Here, we show that both constitutive and agonist-dependent GHSR1a activity elicit a strong impairment of CaV2.1 and CaV2.2 currents in rat and mouse hypothalamic neurons and in a heterologous expression system. Constitutive GHSR1a activity reduces CaV2 currents by a Gi/o-dependent mechanism that involves persistent reduction in channel density at the plasma membrane, whereas ghrelin-dependent GHSR1a inhibition is reversible and involves altered CaV2 gating via a Gq-dependent pathway. Thus, GHSR1a differentially inhibits CaV2 channels by Gi/o or Gq protein pathways depending on its mode of activation. Moreover, we present evidence suggesting that GHSR1a-mediated inhibition of CaV2 attenuates GABA release in hypothalamic neurons, a mechanism that could contribute to neuronal activation through the disinhibition of postsynaptic neurons. PMID:26283199

The Contribution of L-Type Cav1.3 Channels to Retinal Light Responses

PubMed Central

Shi, Liheng; Chang, Janet Ya-An; Yu, Fei; Ko, Michael L.; Ko, Gladys Y.-P.

2017-01-01

L-type voltage-gated calcium channels (LTCCs) regulate tonic neurotransmitter release from sensory neurons including retinal photoreceptors. There are three types of LTCCs (Cav1.2, Cav1.3, and Cav1.4) expressed in the retina. While Cav1.2 is expressed in all retinal cells including the Müller glia and neurons, Cav1.3 and Cav1.4 are expressed in the retinal neurons with Cav1.4 exclusively expressed in the photoreceptor synaptic terminals. Mutations in the gene encoding Cav1.4 cause incomplete X-linked congenital stationary night blindness in humans. Even though Cav1.3 is present in the photoreceptor inner segments and the synaptic terminals in various vertebrate species, its role in vision is unclear, since genetic alterations in Cav1.3 are not associated with severe vision impairment in humans or in Cav1.3-null (Cav1.3−/−) mice. However, a failure to regulate Cav1.3 was found in a mouse model of Usher syndrome, the most common cause of combined deafness and blindness in humans, indicating that Cav1.3 may contribute to retinal function. In this report, we combined physiological and morphological data to demonstrate the role of Cav1.3 in retinal physiology and function that has been undervalued thus far. Through ex vivo and in vivo electroretinogram (ERG) recordings and immunohistochemical staining, we found that Cav1.3 plays a role in retinal light responses and synaptic plasticity. Pharmacological inhibition of Cav1.3 decreased ex vivo ERG a- and b-wave amplitudes. In Cav1.3−/− mice, their dark-adapted ERG a-, b-wave, and oscillatory potential amplitudes were significantly dampened, and implicit times were delayed compared to the wild type (WT). Furthermore, the density of ribbon synapses was reduced in the outer plexiform layer of Cav1.3−/− mice retinas. Hence, Cav1.3 plays a more prominent role in retinal physiology and function than previously reported. PMID:29259539

Modeling, Analysis, and Control of a Hypersonic Vehicle with Significant Aero-Thermo-Elastic-Propulsion Interactions: Elastic, Thermal and Mass Uncertainty

NASA Astrophysics Data System (ADS)

Khatri, Jaidev

This thesis examines themodeling, analysis, and control system design issues for scramjet powered hypersonic vehicles. A nonlinear three degrees of freedom longitudinal model which includes aero-propulsion-elasticity effects was used for all analyses. This model is based upon classical compressible flow and Euler-Bernouli structural concepts. Higher fidelity computational fluid dynamics and finite element methods are needed for more precise intermediate and final evaluations. The methods presented within this thesis were shown to be useful for guiding initial control relevant design. The model was used to examine the vehicle's static and dynamic characteristics over the vehicle's trimmable region. The vehicle has significant longitudinal coupling between the fuel equivalency ratio (FER) and the flight path angle (FPA). For control system design, a two-input two-output plant (FER - elevator to speed-FPA) with 11 states (including 3 flexible modes) was used. Velocity, FPA, and pitch were assumed to be available for feedback. Aerodynamic heat modeling and design for the assumed TPS was incorporated to original Bolender's model to study the change in static and dynamic properties. De-centralized control stability, feasibility and limitations issues were dealt with the change in TPS elasticity, mass and physical dimension. The impact of elasticity due to TPS mass, TPS physical dimension as well as prolonged heating was also analyzed to understand performance limitations of de-centralized control designed for nominal model.

Improving Aerospace Engineering Students' Achievements by an Open Aero Control Experiment Apparatus

ERIC Educational Resources Information Center

Zeng, QingHua; Zhang, WeiHua; Huang, ZheZhi; Dong, RongHua

2014-01-01

This paper describes the development of an aero control experiment apparatus (ACEA) for use in aerospace control practical courses. The ACEA incorporates a systematic multihierarchy learning and teaching method, and was designed to improve aerospace engineering students' understanding of unmanned aerial vehicle (UAV) control systems. It offers a…

A Framework for Evaluating Energy and Emissions of Connected and Automated Vehicles through Traffic Microsimulations

DOT National Transportation Integrated Search

2018-01-07

Connected and automated vehicles (CAV) are poised to transform surface transportation systems in the United States. Near-term CAV technologies like cooperative adaptive cruise control (CACC) have the potential to deliver energy efficiency and air qua...

Potential Energy and Emission Benefits of Vehicle Automation and Connectivity

DOT National Transportation Integrated Search

2017-08-01

Driving behavior greatly impacts vehicle tailpipe emissions. Connected and automated vehicle (CAV) technologies are designed to smooth driving and relieve traffic congestion and are therefore expected to reduce fuel consumption and tailpipe emissions...

High prevalence of antibodies against canine adenovirus (CAV) type 2 in domestic dog populations in South Africa precludes the use of CAV-based recombinant rabies vaccines.

PubMed

Wright, N; Jackson, F R; Niezgoda, M; Ellison, J A; Rupprecht, C E; Nel, L H

2013-08-28

Rabies in dogs can be controlled through mass vaccination. Oral vaccination of domestic dogs would be useful in the developing world, where greater vaccination coverage is needed especially in inaccessible areas or places with large numbers of free-roaming dogs. From this perspective, recent research has focused on development of new recombinant vaccines that can be administered orally in a bait to be used as adjunct for parenteral vaccination. One such candidate, a recombinant canine adenovirus type 2 vaccine expressing the rabies virus glycoprotein (CAV2-RG), is considered a promising option for dogs, given host specificity and safety. To assess the potential use of this vaccine in domestic dog populations, we investigated the prevalence of antibodies against canine adenovirus type 2 in South African dogs. Blood was collected from 241 dogs from the Gauteng and KwaZulu-Natal provinces. Sampled dogs had not previously been vaccinated against canine adenovirus type 1 (CAV1) or canine adenovirus type 2 (CAV2). Animals from both provinces had a high percentage of seropositivity (45% and 62%), suggesting that CAV2 circulates extensively among domestic dog populations in South Africa. Given this finding, we evaluated the effect of pre-existing CAV-specific antibodies on the efficacy of the CAV2-RG vaccine delivered via the oral route in dogs. Purpose-bred Beagle dogs, which received prior vaccination against canine parvovirus, canine distemper virus and CAV, were immunized by oral administration of CAV2-RG. After rabies virus (RABV) infection all animals, except one vaccinated dog, developed rabies. This study demonstrated that pre-existing antibodies against CAV, such as naturally occurs in South African dogs, inhibits the development of neutralizing antibodies against RABV when immunized with a CAV-based rabies recombinant vaccine. Copyright © 2013 Elsevier Ltd. All rights reserved.

Inhibition of Cav3.2 T-type Calcium Channels by Its Intracellular I-II Loop*

PubMed Central

Monteil, Arnaud; Chausson, Patrick; Boutourlinsky, Katia; Mezghrani, Alexandre; Huc-Brandt, Sylvaine; Blesneac, Iulia; Bidaud, Isabelle; Lemmers, Céline; Leresche, Nathalie; Lambert, Régis C.; Lory, Philippe

2015-01-01

Voltage-dependent calcium channels (Cav) of the T-type family (Cav3.1, Cav3.2, and Cav3.3) are activated by low threshold membrane depolarization and contribute greatly to neuronal network excitability. Enhanced T-type channel activity, especially Cav3.2, contributes to disease states, including absence epilepsy. Interestingly, the intracellular loop connecting domains I and II (I-II loop) of Cav3.2 channels is implicated in the control of both surface expression and channel gating, indicating that this I-II loop plays an important regulatory role in T-type current. Here we describe that co-expression of this I-II loop or its proximal region (Δ1-Cav3.2; Ser423–Pro542) together with recombinant full-length Cav3.2 channel inhibited T-type current without affecting channel expression and membrane incorporation. Similar T-type current inhibition was obtained in NG 108-15 neuroblastoma cells that constitutively express Cav3.2 channels. Of interest, Δ1-Cav3.2 inhibited both Cav3.2 and Cav3.1 but not Cav3.3 currents. Efficacy of Δ1-Cav3.2 to inhibit native T-type channels was assessed in thalamic neurons using viral transduction. We describe that T-type current was significantly inhibited in the ventrobasal neurons that express Cav3.1, whereas in nucleus reticularis thalami neurons that express Cav3.2 and Cav3.3 channels, only the fast inactivating T-type current (Cav3.2 component) was significantly inhibited. Altogether, these data describe a new strategy to differentially inhibit Cav3 isoforms of the T-type calcium channels. PMID:25931121

Alternative Splicing Generates a Novel Truncated Cav1.2 Channel in Neonatal Rat Heart*

PubMed Central

Liao, Ping; Yu, Dejie; Hu, Zhenyu; Liang, Mui Cheng; Wang, Jue Jin; Yu, Chye Yun; Ng, Gandi; Yong, Tan Fong; Soon, Jia Lin; Chua, Yeow Leng; Soong, Tuck Wah

2015-01-01

L-type Cav1.2 Ca2+ channel undergoes extensive alternative splicing, generating functionally different channels. Alternatively spliced Cav1.2 Ca2+ channels have been found to be expressed in a tissue-specific manner or under pathological conditions. To provide a more comprehensive understanding of alternative splicing in Cav1.2 channel, we systematically investigated the splicing patterns in the neonatal and adult rat hearts. The neonatal heart expresses a novel 104-bp exon 33L at the IVS3-4 linker that is generated by the use of an alternative acceptor site. Inclusion of exon 33L causes frameshift and C-terminal truncation. Whole-cell electrophysiological recordings of Cav1.233L channels expressed in HEK 293 cells did not detect any current. However, when co-expressed with wild type Cav1.2 channels, Cav1.233L channels reduced the current density and altered the electrophysiological properties of the wild type Cav1.2 channels. Interestingly, the truncated 3.5-domain Cav1.233L channels also yielded a dominant negative effect on Cav1.3 channels, but not on Cav3.2 channels, suggesting that Cavβ subunits is required for Cav1.233L regulation. A biochemical study provided evidence that Cav1.233L channels enhanced protein degradation of wild type channels via the ubiquitin-proteasome system. Although the physiological significance of the Cav1.233L channels in neonatal heart is still unknown, our report demonstrates the ability of this novel truncated channel to modulate the activity of the functional Cav1.2 channels. Moreover, the human Cav1.2 channel also contains exon 33L that is developmentally regulated in heart. Unexpectedly, human exon 33L has a one-nucleotide insertion that allowed in-frame translation of a full Cav1.2 channel. An electrophysiological study showed that human Cav1.233L channel is a functional channel but conducts Ca2+ ions at a much lower level. PMID:25694430

Localization of the calcium channel subunits Cav1.2 (alpha1C) and Cav2.3 (alpha1E) in the mouse organ of Corti.

PubMed

Waka, N; Knipper, M; Engel, J

2003-10-01

Voltage-activated Ca2+ channels play an important role in synaptic transmission, signal processing and development. The immunohistochemical localization of Cav1.2 (alpha1C) and Cav2.3 (alpha1E) Ca2+ channels was studied in the developing and adult mouse organ of Corti using subunit-specific antibodies and fluorescent secondary antibodies with cochlear cryosections. Cav1.2 immunoreactivity has been detected from postnatal day 14 (P14) onwards at the synapses between cholinergic medial efferents and outer hair cells as revealed by co-staining with anti-synaptophysin and anti-choline acetyltransferase. Most likely the Cav1.2 immunoreactivity was located presynaptically at the site of contact of the efferent bouton with the outer hair cell which suggests a role for class C L-type Ca2+ channels in synaptic transmission of the medial efferent system. The localization of the second Ca2+ channel tested, Cav2.3, showed a pronounced change during cochlear development. From P2 until P10, Cav2.3 immunoreactivity was found in the outer spiral bundle followed by the inner spiral bundle, efferent endings and by medial efferent fibers. Around P14, Cav2.3 immunoreactivity disappeared from these structures and from P19 onwards it was observed in the basal poles of the outer hair cell membranes.

Integrating Emerging Data Sources into Operational Practice: Capabilities and Limitations of Devices to Collect, Compile, Save, and Share Messages from CAVs and Connected Travelers

DOT National Transportation Integrated Search

2018-03-01

Connected and automated vehicles (CAVs) and connected travelers will be providing substantially increased levels of data which will be available for agencies to consider using to improve the management and operation of the surface transportation syst...

Overview of NASA Glenn Research Center Programs in Aero-Heat Transfer and Future Needs

NASA Technical Reports Server (NTRS)

Gaugler, Raymond E.

2002-01-01

This presentation concentrates on an overview of the NASA Glenn Research Center and the projects that are supporting Turbine Aero-Heat Transfer Research. The principal areas include the Ultra Efficient Engine Technology (UEET) Project, the Advanced Space Transportation Program (ASTP) Revolutionary Turbine Accelerator (RTA) Turbine Based Combined Cycle (TBCC) project, and the Propulsion & Power Base R&T - Smart Efficient Components (SEC), and Revolutionary Aeropropulsion Concepts (RAC) Projects. In addition, highlights are presented of the turbine aero-heat transfer work currently underway at NASA Glenn, focusing on the use of the Glenn-HT Navier- Stokes code as the vehicle for research in turbulence & transition modeling, grid topology generation, unsteady effects, and conjugate heat transfer.

Numerical method of carbon-based material ablation effects on aero-heating for half-sphere

NASA Astrophysics Data System (ADS)

Wang, Jiang-Feng; Li, Jia-Wei; Zhao, Fa-Ming; Fan, Xiao-Feng

2018-05-01

A numerical method of aerodynamic heating with material thermal ablation effects for hypersonic half-sphere is presented. A surface material ablation model is provided to analyze the ablation effects on aero-thermal properties and structural heat conduction for thermal protection system (TPS) of hypersonic vehicles. To demonstrate its capability, applications for thermal analysis of hypersonic vehicles using carbonaceous ceramic ablators are performed and discussed. The numerical results show the high efficiency and validation of the method developed in thermal characteristics analysis of hypersonic aerodynamic heating.

A survey on the coordination of connected and automated vehicles at intersections and merging at highway on-ramps

DOE PAGES

Rios-Torres, Jackeline; Malikopoulos, Andreas A.

2016-09-07

Connected and automated vehicles (CAVs) have the potential to improve safety by reducing and mitigating traffic accidents. They can also provide opportunities to reduce transportation energy consumption and emissions by improving traffic flow. Vehicle communication with traffic structures and traffic lights can allow individual vehicles to optimize their operation and account for unpredictable changes. This paper summarizes the developments and the research trends in coordination with the CAVs that have been reported in the literature to date. In conclusion, remaining challenges and potential future research directions are also discussed.

Method of making an aero-derivative gas turbine engine

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

Wiebe, David J.

A method of making an aero-derivative gas turbine engine (100) is provided. A combustor outer casing (68) is removed from an existing aero gas turbine engine (60). An annular combustor (84) is removed from the existing aero gas turbine engine. A first row of turbine vanes (38) is removed from the existing aero gas turbine engine. A can annular combustor assembly (122) is installed within the existing aero gas turbine engine. The can annular combustor assembly is configured to accelerate and orient combustion gasses directly onto a first row of turbine blades of the existing aero gas turbine engine. Amore » can annular combustor assembly outer casing (108) is installed to produce the aero-derivative gas turbine engine (100). The can annular combustor assembly is installed within an axial span (85) of the existing aero gas turbine engine vacated by the annular combustor and the first row of turbine vanes.« less

Connected vehicle impacts on transportation planning technical memorandum #6: skills and expertise required to incorporate connected vehicles into transportation planning.

DOT National Transportation Integrated Search

2016-02-08

Professional development and training are essential to the incorporation of connected/automated vehicles (C/AV) into the transportation planning process. In order to guarantee a successful deployment, transportation planning agencies and their stakeh...

Zebrafish CaV2.1 Calcium Channels Are Tailored for Fast Synchronous Neuromuscular Transmission

PubMed Central

Naranjo, David; Wen, Hua; Brehm, Paul

2015-01-01

The CaV2.2 (N-type) and CaV2.1 (P/Q-type) voltage-dependent calcium channels are prevalent throughout the nervous system where they mediate synaptic transmission, but the basis for the selective presence at individual synapses still remains an open question. The CaV2.1 channels have been proposed to respond more effectively to brief action potentials (APs), an idea supported by computational modeling. However, the side-by-side comparison of CaV2.1 and CaV2.2 kinetics in intact neurons failed to reveal differences. As an alternative means for direct functional comparison we expressed zebrafish CaV2.1 and CaV2.2 α-subunits, along with their accessory subunits, in HEK293 cells. HEK cells lack calcium currents, thereby circumventing the need for pharmacological inhibition of mixed calcium channel isoforms present in neurons. HEK cells also have a simplified morphology compared to neurons, which improves voltage control. Our measurements revealed faster kinetics and shallower voltage-dependence of activation and deactivation for CaV2.1. Additionally, recordings of calcium current in response to a command waveform based on the motorneuron AP show, directly, more effective activation of CaV2.1. Analysis of calcium currents associated with the AP waveform indicate an approximately fourfold greater open probability (PO) for CaV2.1. The efficient activation of CaV2.1 channels during APs may contribute to the highly reliable transmission at zebrafish neuromuscular junctions. PMID:25650925

Calmodulin regulates Cav3 T-type channels at their gating brake

PubMed Central

Taiakina, Valentina; Monteil, Arnaud; Piazza, Michael; Guan, Wendy; Stephens, Robert F.; Dieckmann, Thorsten; Guillemette, Joseph Guy; Spafford, J. David

2017-01-01

Calcium (Cav1 and Cav2) and sodium channels possess homologous CaM-binding motifs, known as IQ motifs in their C termini, which associate with calmodulin (CaM), a universal calcium sensor. Cav3 T-type channels, which serve as pacemakers of the mammalian brain and heart, lack a C-terminal IQ motif. We illustrate that T-type channels associate with CaM using co-immunoprecipitation experiments and single particle cryo-electron microscopy. We demonstrate that protostome invertebrate (LCav3) and human Cav3.1, Cav3.2, and Cav3.3 T-type channels specifically associate with CaM at helix 2 of the gating brake in the I–II linker of the channels. Isothermal titration calorimetry results revealed that the gating brake and CaM bind each other with high-nanomolar affinity. We show that the gating brake assumes a helical conformation upon binding CaM, with associated conformational changes to both CaM lobes as indicated by amide chemical shifts of the amino acids of CaM in 1H-15N HSQC NMR spectra. Intact Ca2+-binding sites on CaM and an intact gating brake sequence (first 39 amino acids of the I–II linker) were required in Cav3.2 channels to prevent the runaway gating phenotype, a hyperpolarizing shift in voltage sensitivities and faster gating kinetics. We conclude that the presence of high-nanomolar affinity binding sites for CaM at its universal gating brake and its unique form of regulation via the tuning of the voltage range of activity could influence the participation of Cav3 T-type channels in heart and brain rhythms. Our findings may have implications for arrhythmia disorders arising from mutations in the gating brake or CaM. PMID:28972185

Towards an Aero-Propulso-Servo-Elasticity Analysis of a Commercial Supersonic Transport

NASA Technical Reports Server (NTRS)

Connolly, Joseph W.; Kopasakis, George; Chwalowski, Pawel; Sanetrik, Mark D.; Carlson, Jan-Renee; Silva, Walt A.; McNamara, Jack

2016-01-01

This paper covers the development of an aero-propulso-servo-elastic (APSE) model using computational fluid dynamics (CFD) and linear structural deformations. The APSE model provides the integration of the following two previously developed nonlinear dynamic simulations: a variable cycle turbofan engine and an elastic supersonic commercial transport vehicle. The primary focus of this study is to provide a means to include relevant dynamics of a turbomachinery propulsion system into the aeroelastic studies conducted during a vehicle design, which have historically neglected propulsion effects. A high fidelity CFD tool is used here for the integration platform. The elastic vehicle neglecting the propulsion system serves as a comparison of traditional approaches to the APSE results. An overview of the methodology is presented for integrating the propulsion system and elastic vehicle. Static aeroelastic analysis comparisons between the traditional and developed APSE models for a wing tip detection indicate that the propulsion system impact on the vehicle elastic response could increase the detection by approximately ten percent.

An overview of aeroelasticity studies for the National Aero-Space Plane

NASA Technical Reports Server (NTRS)

Ricketts, Rodney H.; Noll, Thomas E.; Whitlow, Woodrow, Jr.; Huttsell, Lawrence J.

1993-01-01

The National Aero-Space Plane (NASP), or X-30, is a single-stage-to-orbit vehicle that is designed to takeoff and land on conventional runways. Research in aeroelasticity was conducted by the NASA and the Wright Laboratory to support the design of a flight vehicle by the national contractor team. This research includes the development of new computational codes for predicting unsteady aerodynamic pressures. In addition, studies were conducted to determine the aerodynamic heating effects on vehicle aeroelasticity and to determine the effects of fuselage flexibility on the stability of the control systems. It also includes the testing of scale models to better understand the aeroelastic behavior of the X-30 and to obtain data for code validation and correlation. This paper presents an overview of the aeroelastic research which has been conducted to support the airframe design.

Performance Analysis of AeroRP with Ground Station Advertisements

DTIC Science & Technology

2012-03-12

results showed that AeroRP outperforms the traditional MANET routing protocols in terms of throughput and packet delivery ra - tio (PDR) [5, 6]. AeroRP...and waiting for the source to re- send the packet increases the end-to-end delay. The AeroNP corruption indicator and HEC -CRC (header error check...Dev ID | NP HEC CRC-16 | +-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+ \\ \\ / AeroTP Payload

AeroValve Experimental Test Data Final Report

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

Noakes, Mark W.

This report documents the collection of experimental test data and presents performance characteristics for the AeroValve brand prototype pneumatic bidirectional solenoid valves tested at the Oak Ridge National Laboratory (ORNL) in July/August 2014 as part of a validation of AeroValve energy efficiency claims. The test stand and control programs were provided by AeroValve. All raw data and processing are included in the report attachments.

Resolution requirements for aero-optical simulations

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

Mani, Ali; Wang Meng; Moin, Parviz

2008-11-10

Analytical criteria are developed to estimate the error of aero-optical computations due to inadequate spatial resolution of refractive index fields in high Reynolds number flow simulations. The unresolved turbulence structures are assumed to be locally isotropic and at low turbulent Mach number. Based on the Kolmogorov spectrum for the unresolved structures, the computational error of the optical path length is estimated and linked to the resulting error in the computed far-field optical irradiance. It is shown that in the high Reynolds number limit, for a given geometry and Mach number, the spatial resolution required to capture aero-optics within a pre-specifiedmore » error margin does not scale with Reynolds number. In typical aero-optical applications this resolution requirement is much lower than the resolution required for direct numerical simulation, and therefore, a typical large-eddy simulation can capture the aero-optical effects. The analysis is extended to complex turbulent flow simulations in which non-uniform grid spacings are used to better resolve the local turbulence structures. As a demonstration, the analysis is used to estimate the error of aero-optical computation for an optical beam passing through turbulent wake of flow over a cylinder.« less

Down-regulation of CaV1.2 channels during hypertension: how fewer CaV1.2 channels allow more Ca2+ into hypertensive arterial smooth muscle

PubMed Central

Tajada, Sendoa; Cidad, Pilar; Colinas, Olaia; Santana, L Fernando; López-López, José R; Pérez-García, M Teresa

2013-01-01

Hypertension is a clinical syndrome characterized by increased arterial tone. Although the mechanisms are varied, the generally accepted view is that increased CaV1.2 channel function is a common feature of this pathological condition. Here, we investigated the mechanisms underlying vascular dysfunction in a mouse model of genetic hypertension. Contrary to expectation, we found that whole-cell CaV1.2 currents (ICa) were lower in hypertensive (BPH line) than normotensive (BPN line) myocytes. However, local CaV1.2 sparklet activity was higher in BPH cells, suggesting that the relatively low ICa in these cells was produced by a few hyperactive CaV1.2 channels. Furthermore, our data suggest that while the lower expression of the pore-forming α1c subunit of CaV1.2 currents underlies the lower ICa in BPH myocytes, the increased sparklet activity was due to a different composition in the auxiliary subunits of the CaV1.2 complexes. ICa currents in BPN cells were produced by channels composed of α1c/α2δ/β3 subunits, while in BPH myocytes currents were probably generated by the opening of channels formed by α1c/α2δ/β2 subunits. In addition, Ca2+ sparks evoked large conductance, Ca2+-activated K+ (BK) currents of lower magnitude in BPH than in BPN myocytes, because BK channels were less sensitive to Ca2+. Our data are consistent with a model in which a decrease in the global number of CaV1.2 currents coexist with the existence of a subpopulation of highly active channels that dominate the resting Ca2+ influx. The decrease in BK channel activity makes the hyperpolarizing brake ineffective and leads BPH myocytes to a more contracted resting state. PMID:24167226

BIN1 is Reduced and Cav1.2 Trafficking is Impaired in Human Failing Cardiomyocytes

PubMed Central

Hong, Ting-Ting; Smyth, James W.; Chu, Kevin Y.; Vogan, Jacob M.; Fong, Tina S.; Jensen, Brian C.; Fang, Kun; Halushka, Marc K.; Russell, Stuart D.; Colecraft, Henry; Hoopes, Charles W.; Ocorr, Karen; Chi, Neil C.; Shaw, Robin M.

2011-01-01

Background Heart failure is a growing epidemic and a typical aspect of heart failure pathophysiology is altered calcium transients. Normal cardiac calcium transients are initiated by Cav1.2 channels at cardiac T-tubules. BIN1 is a membrane scaffolding protein that causes Cav1.2 to traffic to T-tubules in healthy hearts. The mechanisms of Cav1.2 trafficking in heart failure are not known. Objective To study BIN1 expression and its effect on Cav1.2 trafficking in failing hearts. Methods Intact myocardium and freshly isolated cardiomyocytes from non-failing and end-stage failing human hearts were used to study BIN1 expression and Cav1.2 localization. To confirm Cav1.2 surface expression dependence on BIN1, patch clamp recordings were performed of Cav1.2 current in cell lines with and without trafficking competent BIN1. Also, in adult mouse cardiomyocytes, surface Cav1.2 and calcium transients were studied after shRNA mediated knockdown of BIN1. For a functional readout in intact heart, calcium transients and cardiac contractility were analyzed in a zebrafish model with morpholino mediated knockdown of BIN1. Results BIN1 expression is significantly decreased in failing cardiomyocytes at both mRNA (30% down) and protein (36% down) levels. Peripheral Cav1.2 is reduced 42% by imaging and biochemical T-tubule fraction of Cav1.2 is reduced 68%. Total calcium current is reduced 41% in a cell line expressing non-trafficking BIN1 mutant. In mouse cardiomyocytes, BIN1 knockdown decreases surface Cav1.2 and impairs calcium transients. In zebrafish hearts, BIN1 knockdown causes a 75% reduction in calcium transients and severe ventricular contractile dysfunction. Conclusions The data indicate that BIN1 is significantly reduced in human heart failure, and this reduction impairs Cav1.2 trafficking, calcium transients, and contractility. PMID:22138472

Estimated Bounds and Important Factors for Fuel Use and Consumer Costs of Connected and Automated Vehicles

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

Stephens, T. S.; Gonder, Jeff; Chen, Yuche

This report details a study of the potential effects of connected and automated vehicle (CAV) technologies on vehicle miles traveled (VMT), vehicle fuel efficiency, and consumer costs. Related analyses focused on a range of light-duty CAV technologies in conventional powertrain vehicles -- from partial automation to full automation, with and without ridesharing -- compared to today's base-case scenario. Analysis results revealed widely disparate upper- and lower-bound estimates for fuel use and VMT, ranging from a tripling of fuel use to decreasing light-duty fuel use to below 40% of today's level. This wide range reflects uncertainties in the ways that CAVmore » technologies can influence vehicle efficiency and use through changes in vehicle designs, driving habits, and travel behavior. The report further identifies the most significant potential impacting factors, the largest areas of uncertainty, and where further research is particularly needed.« less

Extinction of Contextual Cocaine Memories Requires Cav1.2 within D1R-Expressing Cells and Recruits Hippocampal Cav1.2-Dependent Signaling Mechanisms

PubMed Central

Lee, Anni S.; Fischer, Delaney K.; Van Kempen, Tracey A.; Mudragel, Vladimir; Glass, Michael J.

2017-01-01

Exposure to cocaine-associated contextual cues contributes significantly to relapse. Extinction of these contextual associations, which involves a new form of learning, reduces cocaine-seeking behavior; however, the molecular mechanisms underlying this process remain largely unknown. We report that extinction, but not acquisition, of cocaine conditioned place preference (CPP) in male mice increased Cav1.2 L-type Ca2+ channel mRNA and protein in postsynaptic density (PSD) fractions of the hippocampus, a brain region involved in drug–context associations. Moreover, viral-mediated deletion of Cav1.2 in the dorsal hippocampus attenuated extinction of cocaine CPP. Molecular studies examining downstream Cav1.2 targets revealed that extinction recruited calcium/calmodulin (Ca2+/CaMK)-dependent protein kinase II (CaMKII) to the hippocampal PSD. This occurred in parallel with an increase in phosphorylation of the AMPA GluA1 receptor subunit at serine 831 (S831), a CaMKII site, along with an increase in total PSD GluA1. The necessity of S831 GluA1 was further demonstrated by the lack of extinction in S831A GluA1 phosphomutant mice. Of note hippocampal GluA1 levels remained unaltered at the PSD, but were reduced near the PSD and at perisynaptic sites of dendritic spines in extinction-resistant S831A mutant mice. Finally, conditional knock-out of Cav1.2 in dopamine D1 receptor (D1R)-expressing cells resulted in attenuation of cocaine CPP extinction and lack of extinction-dependent changes in hippocampal PSD CaMKII expression and S831 GluA1 phosphorylation. In summary, we demonstrate an essential role for the hippocampal Cav1.2/CaMKII/S831 GluA1 pathway in cocaine CPP extinction, with data supporting contribution of hippocampal D1R-expressing cells in this process. These findings demonstrate a novel role for Cav1.2 channels in extinction of contextual cocaine-associated memories. SIGNIFICANCE STATEMENT Continued drug-seeking behavior, a defining characteristic of cocaine

Aeronautical Mobile Airport Communications System (AeroMACS)

NASA Technical Reports Server (NTRS)

Budinger, James M.; Hall, Edward

2011-01-01

To help increase the capacity and efficiency of the nation s airports, a secure wideband wireless communications system is proposed for use on the airport surface. This paper provides an overview of the research and development process for the Aeronautical Mobile Airport Communications System (AeroMACS). AeroMACS is based on a specific commercial profile of the Institute of Electrical and Electronics Engineers (IEEE) 802.16 standard known as Wireless Worldwide Interoperability for Microwave Access or WiMAX (WiMax Forum). The paper includes background on the need for global interoperability in air/ground data communications, describes potential AeroMACS applications, addresses allocated frequency spectrum constraints, summarizes the international standardization process, and provides findings and recommendations from the world s first AeroMACS prototype implemented in Cleveland, Ohio, USA.

Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma

PubMed Central

Thorleifsson, Gudmar; Walters, G Bragi; Hewitt, Alex W; Masson, Gisli; Helgason, Agnar; DeWan, Andrew; Sigurdsson, Asgeir; Jonasdottir, Adalbjorg; Gudjonsson, Sigurjon A; Magnusson, Kristinn P; Stefansson, Hreinn; Lam, Dennis S C; Tam, Pancy O S; Gudmundsdottir, Gudrun J; Southgate, Laura; Burdon, Kathryn P; Gottfredsdottir, Maria Soffia; Aldred, Micheala A; Mitchell, Paul; St Clair, David; Collier, David A; Tang, Nelson; Sveinsson, Orn; Macgregor, Stuart; Martin, Nicholas G; Cree, Angela J; Gibson, Jane; MacLeod, Alex; Jacob, Aby; Ennis, Sarah; Young, Terri L; Chan, Juliana C N; Karwatowski, Wojciech S S; Hammond, Christopher J; Thordarson, Kristjan; Zhang, Mingzhi; Wadelius, Claes; Lotery, Andrew J; Trembath, Richard C; Pang, Chi Pui; Hoh, Josephine; Craig, Jamie E; Kong, Augustine; Mackey, David A; Jonasson, Fridbert; Thorsteinsdottir, Unnur; Stefansson, Kari

2011-01-01

We conducted a genome-wide association study for primary open-angle glaucoma (POAG) in 1,263 affected individuals (cases) and 34,877 controls from Iceland. We identified a common sequence variant at 7q31 (rs4236601[A], odds ratio (OR) = 1.36, P = 5.0 × 10-10). We then replicated the association in sample sets of 2,175 POAG cases and 2,064 controls from Sweden, the UK and Australia (combined OR = 1.18, P = 0.0015) and in 299 POAG cases and 580 unaffected controls from Hong Kong and Shantou, China (combined OR = 5.42, P = 0.0021). The risk variant identified here is located close to CAV1 and CAV2, both of which are expressed in the trabecular meshwork and retinal ganglion cells that are involved in the pathogenesis of POAG. PMID:20835238

BIN1 is reduced and Cav1.2 trafficking is impaired in human failing cardiomyocytes.

PubMed

Hong, Ting-Ting; Smyth, James W; Chu, Kevin Y; Vogan, Jacob M; Fong, Tina S; Jensen, Brian C; Fang, Kun; Halushka, Marc K; Russell, Stuart D; Colecraft, Henry; Hoopes, Charles W; Ocorr, Karen; Chi, Neil C; Shaw, Robin M

2012-05-01

Heart failure is a growing epidemic, and a typical aspect of heart failure pathophysiology is altered calcium transients. Normal cardiac calcium transients are initiated by Cav1.2 channels at cardiac T tubules. Bridging integrator 1 (BIN1) is a membrane scaffolding protein that causes Cav1.2 to traffic to T tubules in healthy hearts. The mechanisms of Cav1.2 trafficking in heart failure are not known. To study BIN1 expression and its effect on Cav1.2 trafficking in failing hearts. Intact myocardium and freshly isolated cardiomyocytes from nonfailing and end-stage failing human hearts were used to study BIN1 expression and Cav1.2 localization. To confirm Cav1.2 surface expression dependence on BIN1, patch-clamp recordings were performed of Cav1.2 current in cell lines with and without trafficking-competent BIN1. Also, in adult mouse cardiomyocytes, surface Cav1.2 and calcium transients were studied after small hairpin RNA-mediated knockdown of BIN1. For a functional readout in intact heart, calcium transients and cardiac contractility were analyzed in a zebrafish model with morpholino-mediated knockdown of BIN1. BIN1 expression is significantly decreased in failing cardiomyocytes at both mRNA (30% down) and protein (36% down) levels. Peripheral Cav1.2 is reduced to 42% by imaging, and a biochemical T-tubule fraction of Cav1.2 is reduced to 68%. The total calcium current is reduced to 41% in a cell line expressing a nontrafficking BIN1 mutant. In mouse cardiomyocytes, BIN1 knockdown decreases surface Cav1.2 and impairs calcium transients. In zebrafish hearts, BIN1 knockdown causes a 75% reduction in calcium transients and severe ventricular contractile dysfunction. The data indicate that BIN1 is significantly reduced in human heart failure, and this reduction impairs Cav1.2 trafficking, calcium transients, and contractility. Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Calmodulin overexpression does not alter Cav1.2 function or oligomerization state.

PubMed

Findeisen, Felix; Tolia, Alexandra; Arant, Ryan; Kim, Eun Young; Isacoff, Ehud; Minor, Daniel L

2011-01-01

Interactions between calmodulin (CaM) and voltage-gated calcium channels (Ca(v)s) are crucial for Ca(v) activity-dependent feedback modulation. We recently reported an X-ray structure that shows two Ca(2+)/CaM molecules bound to the Ca(v)1.2 C terminal tail, one at the PreIQ region and one at the IQ domain. Surprisingly, the asymmetric unit of the crystal showed a dimer in which Ca(2+)/CaM bridged two PreIQ helixes to form a 4:2 Ca(2+)/CaM:Ca(v) C-terminal tail assembly. Contrary to previous proposals based on a similar crystallographic dimer, extensive biochemical analysis together with subunit counting experiments of full-length channels in live cell membranes failed to find evidence for multimers that would be compatible with the 4:2 crossbridged complex. Here, we examine this possibility further. We find that CaM over-expression has no functional effect on Ca(v)1.2 inactivation or on the stoichiometry of full-length Ca(v)1.2. These data provide further support for the monomeric Ca(v)1.2 stoichiometry. Analysis of the electrostatic surfaces of the 2:1 Ca(2+)/CaM:Ca(V) C-terminal tail assembly reveals notable patches of electronegativity. These could influence various forms of channel modulation by interacting with positively charged elements from other intracellular channel domains.

The CaV2.3 R-type voltage-gated Ca2+ channel in mouse sleep architecture.

PubMed

Siwek, Magdalena Elisabeth; Müller, Ralf; Henseler, Christina; Broich, Karl; Papazoglou, Anna; Weiergräber, Marco

2014-05-01

Voltage-gated Ca(2+) channels (VGCCs) are key elements in mediating thalamocortical rhythmicity. Low-voltage activated (LVA) CaV 3 T-type Ca(2+) channels have been related to thalamic rebound burst firing and to generation of non-rapid eye movement (NREM) sleep. High-voltage activated (HVA) CaV 1 L-type Ca(2+) channels, on the opposite, favor the tonic mode of action associated with higher levels of vigilance. However, the role of the HVA Non-L-type CaV2.3 Ca(2+) channels, which are predominantly expressed in the reticular thalamic nucleus (RTN), still remains unclear. Recently, CaV2.3(-/-) mice were reported to exhibit altered spike-wave discharge (SWD)/absence seizure susceptibility supported by the observation that CaV2.3 mediated Ca(2+) influx into RTN neurons can trigger small-conductance Ca(2+)-activated K(+)-channel type 2 (SK2) currents capable of maintaining thalamic burst activity. Based on these studies we investigated the role of CaV2.3 R-type Ca(2+) channels in rodent sleep. The role of CaV2.3 Ca(2+) channels was analyzed in CaV2.3(-/-) mice and controls in both spontaneous and artificial urethane-induced sleep, using implantable video-EEG radiotelemetry. Data were analyzed for alterations in sleep architecture using sleep staging software and time-frequency analysis. CaV2.3 deficient mice exhibited reduced wake duration and increased slow-wave sleep (SWS). Whereas mean sleep stage durations remained unchanged, the total number of SWS epochs was increased in CaV2.3(-/-) mice. Additional changes were observed for sleep stage transitions and EEG amplitudes. Furthermore, urethane-induced SWS mimicked spontaneous sleep results obtained from CaV2.3 deficient mice. Quantitative Real-time PCR did not reveal changes in thalamic CaV3 T-type Ca(2+) channel expression. The detailed mechanisms of SWS increase in CaV2.3(-/-) mice remain to be determined. Low-voltage activated CaV2.3 R-type Ca(2+) channels in the thalamocortical loop and extra

PREFACE: 9th International Symposium on Cavitation (CAV2015)

NASA Astrophysics Data System (ADS)

Farhat, M.; Müller, A.

2015-12-01

It is our pleasure and privilege to welcome all the participants of the 9th International Symposium on Cavitation (CAV2015) to Lausanne. Since its initiation in 1986 in Sendai, Japan, the CAV symposium has grown to become the world's foremost event dedicated to cavitation. Hosted by EPFL (Ecole Polytechnique Fédérale de Lausanne) and staged at the SwissTech Convention Center, CAV2015 is a unique opportunity to exchange with leading scientists and industry experts about the latest advances in theoretical modelling, numerical simulation and experimentation related to cavitation phenomena with a special emphasis on practical applications. The topics covered by CAV2015 include cavitation in ¬fluid machinery and fuel systems, bubble dynamics, cavitation erosion, advanced numerical simulation, sonochemistery, biomedicine and experimental techniques. CAV2015 will also host an exhibition of leading providers of state of the art measurement equipment, including high-speed imaging systems, non-intrusive velocimetry, pressure sensors, as well as numerical solvers. We have accepted over 190 papers, which will be presented in four parallel sessions. The proceedings will appear in the open access Journal of Physics: Conference Series (JPCS), which is part of the IOP Conference Series. All published papers are fully citable and upon publication will be free to download in perpetuity. We would like to thank all the reviewers for their great help during the selection process. We will also propose six plenary speakers to highlight cavitation issues in different fields. Finally, we would like to warmly thank our sponsors for their valuable support and the local Organizing Committee for the efforts in setting up this important event. We look forward to seeing you in Lausanne!

NASA's Aero-Space Technology

NASA Technical Reports Server (NTRS)

Milstead, Phil

2000-01-01

This presentation reviews the three pillars and the associated goals of NASA's Aero-Space Technology Enterprise. The three pillars for success are: (1) Global Civil Aviation, (2) Revolutionary Technology Leaps, (3) Advanced Space Transportation. The associated goals of the first pillar are to reduce accidents, emissions, and cost, and to increase the aviation system capacity. The goals of the second pillar are to reduce transoceanic travel time, revolutionize general aviation aircraft, and improve development capacity. The goals associated with the third pillar are to reduce the launch cost for low earth orbit and to reduce travel time for planetary missions. In order to meet these goals NASA must provide next-generation design capability for new and or experimental craft which enable a balance between reducing components of the design cycle by up to 50% and or increasing the confidence in design by 50%. These next-generation design tools, concepts, and processes will revolutionize vehicle development. The presentation finally reviews the importance of modeling and simulation in achieving the goals.

Modulation of Ca(v)3.1 T-type Ca2+ channels by the ran binding protein RanBPM.

PubMed

Kim, Taehyun; Kim, Sunoh; Yun, Hyung-Mun; Chung, Kwang Chul; Han, Ye Sun; Shin, Hee-Sup; Rhim, Hyewhon

2009-01-02

In order to study the currently unknown cellular signaling pathways of Ca(v)3.1 T-type Ca(2+) channels (Ca(v)3.1 channels), we performed a yeast two-hybrid screening using intracellular domains of Ca(v)3.1 alpha1 subunit as bait. After screening the human brain cDNA library, several proteins, including RanBPM, were identified as interacting with Ca(v)3.1 channels. RanBPM was found to bind to the cytoplasmic intracellular loop between transmembrane domains I and II of Ca(v)3.1 channels. Using whole-cell patch-clamp techniques, we found that Ca(v)3.1 currents were increased by the expression of RanBPM in HEK293/Ca(v)3.1 cells. We next examined whether RanBPM affected the biophysical properties and plasma membrane expression of Ca(v)3.1 channels. Furthermore, we showed that the PKC activator inhibited Ca(v)3.1 currents, an effect that was abolished by the expression of RanBPM. These results suggest that RanBPM could be a key regulator of Ca(v)3.1 channel-mediated signaling pathways.

The CaV2.3 R-Type Voltage-Gated Ca2+ Channel in Mouse Sleep Architecture

PubMed Central

Siwek, Magdalena Elisabeth; Müller, Ralf; Henseler, Christina; Broich, Karl; Papazoglou, Anna; Weiergräber, Marco

2014-01-01

Study Objectives: Voltage-gated Ca2+ channels (VGCCs) are key elements in mediating thalamocortical rhythmicity. Low-voltage activated (LVA) CaV 3 T-type Ca2+ channels have been related to thalamic rebound burst firing and to generation of non-rapid eye movement (NREM) sleep. High-voltage activated (HVA) CaV 1 L-type Ca2+ channels, on the opposite, favor the tonic mode of action associated with higher levels of vigilance. However, the role of the HVA Non-L-type CaV2.3 Ca2+ channels, which are predominantly expressed in the reticular thalamic nucleus (RTN), still remains unclear. Recently, CaV2.3−/− mice were reported to exhibit altered spike-wave discharge (SWD)/absence seizure susceptibility supported by the observation that CaV2.3 mediated Ca2+ influx into RTN neurons can trigger small-conductance Ca2+-activated K+-channel type 2 (SK2) currents capable of maintaining thalamic burst activity. Based on these studies we investigated the role of CaV2.3 R-type Ca2+ channels in rodent sleep. Methods: The role of CaV2.3 Ca2+ channels was analyzed in CaV2.3−/− mice and controls in both spontaneous and artificial urethane-induced sleep, using implantable video-EEG radiotelemetry. Data were analyzed for alterations in sleep architecture using sleep staging software and time-frequency analysis. Results: CaV2.3 deficient mice exhibited reduced wake duration and increased slow-wave sleep (SWS). Whereas mean sleep stage durations remained unchanged, the total number of SWS epochs was increased in CaV2.3−/− mice. Additional changes were observed for sleep stage transitions and EEG amplitudes. Furthermore, urethane-induced SWS mimicked spontaneous sleep results obtained from CaV2.3 deficient mice. Quantitative Real-time PCR did not reveal changes in thalamic CaV3 T-type Ca2+ channel expression. The detailed mechanisms of SWS increase in CaV2.3−/− mice remain to be determined. Conclusions: Low-voltage activated CaV2.3 R-type Ca2+ channels in the thalamocortical

Vibration modelling and verifications for whole aero-engine

NASA Astrophysics Data System (ADS)

Chen, G.

2015-08-01

In this study, a new rotor-ball-bearing-casing coupling dynamic model for a practical aero-engine is established. In the coupling system, the rotor and casing systems are modelled using the finite element method, support systems are modelled as lumped parameter models, nonlinear factors of ball bearings and faults are included, and four types of supports and connection models are defined to model the complex rotor-support-casing coupling system of the aero-engine. A new numerical integral method that combines the Newmark-β method and the improved Newmark-β method (Zhai method) is used to obtain the system responses. Finally, the new model is verified in three ways: (1) modal experiment based on rotor-ball bearing rig, (2) modal experiment based on rotor-ball-bearing-casing rig, and (3) fault simulations for a certain type of missile turbofan aero-engine vibration. The results show that the proposed model can not only simulate the natural vibration characteristics of the whole aero-engine but also effectively perform nonlinear dynamic simulations of a whole aero-engine with faults.

Connected Vehicle Impacts on Transportation Planning—Outreach to Planning Community.

DOT National Transportation Integrated Search

2016-06-01

This document presents outreach memos on 11 case studies analyzing the impacts of connected and automated vehicles (C/AV) on transportation planning products. These 11 case studies are documented indepth in the associated project document entitled Co...

The voltage gated Ca(2+)-channel Cav3.2 and therapeutic responses in breast cancer.

PubMed

Pera, Elena; Kaemmerer, Elke; Milevskiy, Michael J G; Yapa, Kunsala T D S; O'Donnell, Jake S; Brown, Melissa A; Simpson, Fiona; Peters, Amelia A; Roberts-Thomson, Sarah J; Monteith, Gregory R

2016-01-01

Understanding the cause of therapeutic resistance and identifying new biomarkers in breast cancer to predict therapeutic responses will help optimise patient care. Calcium (Ca(2+))-signalling is important in a variety of processes associated with tumour progression, including breast cancer cell migration and proliferation. Ca(2+)-signalling is also linked to the acquisition of multidrug resistance. This study aimed to assess the expression level of proteins involved in Ca(2+)-signalling in an in vitro model of trastuzumab-resistance and to assess the ability of identified targets to reverse resistance and/or act as potential biomarkers for prognosis or therapy outcome. Expression levels of a panel of Ca(2+)-pumps, channels and channel regulators were assessed using RT-qPCR in resistant and sensitive age-matched SKBR3 breast cancer cells, established through continuous culture in the absence or presence of trastuzumab. The role of Cav3.2 in the acquisition of trastuzumab-resistance was assessed through pharmacological inhibition and induced overexpression. Levels of Cav3.2 were assessed in a panel of non-malignant and malignant breast cell lines using RT-qPCR and in patient samples representing different molecular subtypes (PAM50 cohort). Patient survival was also assessed in samples stratified by Cav3.2 expression (METABRIC and KM-Plotter cohort). Increased mRNA of Cav3.2 was a feature of both acquired and intrinsic trastuzumab-resistant SKBR3 cells. However, pharmacological inhibition of Cav3.2 did not restore trastuzumab-sensitivity nor did Cav3.2 overexpression induce the expression of markers associated with resistance, suggesting that Cav3.2 is not a driver of trastuzumab-resistance. Cav3.2 levels were significantly higher in luminal A, luminal B and HER2-enriched subtypes compared to the basal subtype. High levels of Cav3.2 were associated with poor outcome in patients with oestrogen receptor positive (ER+) breast cancers, whereas Cav3.2 levels were

Aero-servo-viscoelasticity theory: Lifting surfaces, plates, velocity transients, flutter, and instability

NASA Astrophysics Data System (ADS)

Merrett, Craig G.

Modern flight vehicles are fabricated from composite materials resulting in flexible structures that behave differently from the more traditional elastic metal structures. Composite materials offer a number of advantages compared to metals, such as improved strength to mass ratio, and intentional material property anisotropy. Flexible aircraft structures date from the Wright brothers' first aircraft with fabric covered wooden frames. The flexibility of the structure was used to warp the lifting surface for flight control, a concept that has reappeared as aircraft morphing. These early structures occasionally exhibited undesirable characteristics during flight such as interactions between the empennage and the aft fuselage, or control problems with the elevators. The research to discover the cause and correction of these undesirable characteristics formed the first foray into the field of aeroelasticity. Aeroelasticity is the intersection and interaction between aerodynamics, elasticity, and inertia or dynamics. Aeroelasticity is well suited for metal aircraft, but requires expansion to improve its applicability to composite vehicles. The first is a change from elasticity to viscoelasticity to more accurately capture the solid mechanics of the composite material. The second change is to include control systems. While the inclusion of control systems in aeroelasticity lead to aero-servo-elasticity, more control possibilities exist for a viscoelastic composite material. As an example, during the lay-up of carbon-epoxy plies, piezoelectric control patches are inserted between different plies to give a variety of control options. The expanded field is called aero-servo-viscoelasticity. The phenomena of interest in aero-servo-viscoelasticity are best classified according to the type of structure considered, either a lifting surface or a panel, and the type of dynamic stability present. For both types of structures, the governing equations are integral

Sensor fault diagnosis of aero-engine based on divided flight status.

PubMed

Zhao, Zhen; Zhang, Jun; Sun, Yigang; Liu, Zhexu

2017-11-01

Fault diagnosis and safety analysis of an aero-engine have attracted more and more attention in modern society, whose safety directly affects the flight safety of an aircraft. In this paper, the problem concerning sensor fault diagnosis is investigated for an aero-engine during the whole flight process. Considering that the aero-engine is always working in different status through the whole flight process, a flight status division-based sensor fault diagnosis method is presented to improve fault diagnosis precision for the aero-engine. First, aero-engine status is partitioned according to normal sensor data during the whole flight process through the clustering algorithm. Based on that, a diagnosis model is built for each status using the principal component analysis algorithm. Finally, the sensors are monitored using the built diagnosis models by identifying the aero-engine status. The simulation result illustrates the effectiveness of the proposed method.

Sensor fault diagnosis of aero-engine based on divided flight status

NASA Astrophysics Data System (ADS)

Zhao, Zhen; Zhang, Jun; Sun, Yigang; Liu, Zhexu

2017-11-01

Fault diagnosis and safety analysis of an aero-engine have attracted more and more attention in modern society, whose safety directly affects the flight safety of an aircraft. In this paper, the problem concerning sensor fault diagnosis is investigated for an aero-engine during the whole flight process. Considering that the aero-engine is always working in different status through the whole flight process, a flight status division-based sensor fault diagnosis method is presented to improve fault diagnosis precision for the aero-engine. First, aero-engine status is partitioned according to normal sensor data during the whole flight process through the clustering algorithm. Based on that, a diagnosis model is built for each status using the principal component analysis algorithm. Finally, the sensors are monitored using the built diagnosis models by identifying the aero-engine status. The simulation result illustrates the effectiveness of the proposed method.

Overview of recent aero-optics flight tests

NASA Technical Reports Server (NTRS)

Otten, L. J., III

1980-01-01

A chronological overview of aero-optics test flights is presented highlighting the objectives and conclusions from the tests. Flight tests performed in coordination with the PRESS reentry observation missions and the ALL Cycle 2 laser propagation and tracking demonstrations are described addressing the identification and quantification of distortion phenomena. Finally, current aero-optics flight investigations of an atmospheric turbulence probe are briefly discussed.

Exclusion of alternative exon 33 of CaV1.2 calcium channels in heart is proarrhythmogenic

PubMed Central

Li, Guang; Wang, Juejin; Liao, Ping; Bartels, Peter; Zhang, Hengyu; Yu, Dejie; Liang, Mui Cheng; Poh, Kian Keong; Yu, Chye Yun; Jiang, Fengli; Yong, Tan Fong; Wong, Yuk Peng; Hu, Zhenyu; Huang, Hua; Zhang, Guangqin; Galupo, Mary Joyce; Bian, Jin-Song; Ponniah, Sathivel; Trasti, Scott Lee; Foo, Roger; Hoppe, Uta C.; Herzig, Stefan; Soong, Tuck Wah

2017-01-01

Alternative splicing changes the CaV1.2 calcium channel electrophysiological property, but the in vivo significance of such altered channel function is lacking. Structure–function studies of heterologously expressed CaV1.2 channels could not recapitulate channel function in the native milieu of the cardiomyocyte. To address this gap in knowledge, we investigated the role of alternative exon 33 of the CaV1.2 calcium channel in heart function. Exclusion of exon 33 in CaV1.2 channels has been reported to shift the activation potential −10.4 mV to the hyperpolarized direction, and increased expression of CaV1.2Δ33 channels was observed in rat myocardial infarcted hearts. However, how a change in CaV1.2 channel electrophysiological property, due to alternative splicing, might affect cardiac function in vivo is unknown. To address these questions, we generated mCacna1c exon 33−/−-null mice. These mice contained CaV1.2Δ33 channels with a gain-of-function that included conduction of larger currents that reflects a shift in voltage dependence and a modest increase in single-channel open probability. This altered channel property underscored the development of ventricular arrhythmia, which is reflected in significantly more deaths of exon 33−/− mice from β-adrenergic stimulation. In vivo telemetric recordings also confirmed increased frequencies in premature ventricular contractions, tachycardia, and lengthened QT interval. Taken together, the significant decrease or absence of exon 33-containing CaV1.2 channels is potentially proarrhythmic in the heart. Of clinical relevance, human ischemic and dilated cardiomyopathy hearts showed increased inclusion of exon 33. However, the possible role that inclusion of exon 33 in CaV1.2 channels may play in the pathogenesis of human heart failure remains unclear. PMID:28490495

CaV3.1 is a tremor rhythm pacemaker in the inferior olive

PubMed Central

Park, Young-Gyun; Park, Hye-Yeon; Lee, C. Justin; Choi, Soonwook; Jo, Seonmi; Choi, Hansol; Kim, Yang-Hann; Shin, Hee-Sup; Llinas, Rodolfo R.; Kim, Daesoo

2010-01-01

The rhythmic motor pathway activation by pacemaker neurons or circuits in the brain has been proposed as the mechanism for the timing of motor coordination, and the abnormal potentiation of this mechanism may lead to a pathological tremor. Here, we show that the potentiation of CaV3.1 T-type Ca2+ channels in the inferior olive contributes to the onset of the tremor in a pharmacological model of essential tremor. After administration of harmaline, 4- to 10-Hz synchronous neuronal activities arose from the IO and then propagated to cerebellar motor circuits in wild-type mice, but those rhythmic activities were absent in mice lacking CaV3.1 gene. Intracellular recordings in brain-stem slices revealed that the CaV3.1-deficient inferior olive neurons lacked the subthreshold oscillation of membrane potentials and failed to trigger 4- to 10-Hz rhythmic burst discharges in the presence of harmaline. In addition, the selective knockdown of CaV3.1 gene in the inferior olive by shRNA efficiently suppressed the harmaline-induced tremor in wild-type mice. A mathematical model constructed based on data obtained from patch-clamping experiments indicated that harmaline could efficiently potentiate CaV3.1 channels by changing voltage-dependent responsiveness in the hyperpolarizing direction. Thus, CaV3.1 is a molecular pacemaker substrate for intrinsic neuronal oscillations of inferior olive neurons, and the potentiation of this mechanism can be considered as a pathological cause of essential tremor. PMID:20498062

THE TREATMENT OF AERO-OTITIS MEDIA BY REDECOMPRESSION,

DTIC Science & Technology

The precipitating event preceding the appearance of aero- otitis media is the development of a relative vacuum within the middle ear. The aim of...obtaining normal pressure relationships between the middle ear and the environment. In 27 of a group of 33 men with severe aero- otitis media , this

Alternative Splicing in CaV2.2 Regulates Neuronal Trafficking via Adaptor Protein Complex-1 Adaptor Protein Motifs

PubMed Central

Macabuag, Natsuko

2015-01-01

N-type voltage-gated calcium (CaV2.2) channels are expressed in neurons and targeted to the plasma membrane of presynaptic terminals, facilitating neurotransmitter release. Here, we find that the adaptor protein complex-1 (AP-1) mediates trafficking of CaV2.2 from the trans-Golgi network to the cell surface. Examination of splice variants of CaV2.2, containing either exon 37a (selectively expressed in nociceptors) or 37b in the proximal C terminus, reveal that canonical AP-1 binding motifs, YxxΦ and [DE]xxxL[LI], present only in exon 37a, enhance intracellular trafficking of exon 37a-containing CaV2.2 to the axons and plasma membrane of rat DRG neurons. Finally, we identify differential effects of dopamine-2 receptor (D2R) and its agonist-induced activation on trafficking of CaV2.2 isoforms. D2R slowed the endocytosis of CaV2.2 containing exon 37b, but not exon 37a, and activation by the agonist quinpirole reversed the effect of the D2R. Our work thus reveals key mechanisms involved in the trafficking of N-type calcium channels. SIGNIFICANCE STATEMENT CaV2.2 channels are important for neurotransmitter release, but how they are trafficked is still poorly understood. Here, we describe a novel mechanism for trafficking of CaV2.2 from the trans-Golgi network to the cell surface which is mediated by the adaptor protein AP-1. Alternative splicing of exon 37 produces CaV2.2-exon 37a, selectively expressed in nociceptors, or CaV2.2-exon 37b, which is the major splice isoform. Our study reveals that canonical AP-1 binding motifs (YxxΦ and [DE]xxxL[LI]), present in exon 37a, but not 37b, enhance intracellular trafficking of exon 37a-containing CaV2.2 to axons and plasma membrane of DRG neurons. Interaction of APs with CaV2.2 channels may also be key underlying mechanisms for differential effects of the dopamine D2 receptor on trafficking of CaV2.2 splice variants. PMID:26511252

AeroDyn V15.04: Design tool for wind and MHK turbines

DOE Data Explorer

Murray, Robynne; Hayman, Greg; Jonkman, Jason

2017-04-28

AeroDyn is a time-domain wind and MHK turbine aerodynamics module that can be coupled into the FAST version 8 multi-physics engineering tool to enable aero-elastic simulation of horizontal-axis wind turbines. AeroDyn V15.04 has been updated to include a cavitation check for MHK turbines, and can be driven as a standalone code to compute wind turbine aerodynamic response uncoupled from FAST. Note that while AeroDyn has been updated to v15.04, FAST v8.16 has not yet been updated and still uses AeroDyn v15.03.

Functional Properties of a Newly Identified C-terminal Splice Variant of Cav1.3 L-type Ca2+ Channels*

PubMed Central

Bock, Gabriella; Gebhart, Mathias; Scharinger, Anja; Jangsangthong, Wanchana; Busquet, Perrine; Poggiani, Chiara; Sartori, Simone; Mangoni, Matteo E.; Sinnegger-Brauns, Martina J.; Herzig, Stefan; Striessnig, Jörg; Koschak, Alexandra

2011-01-01

An intramolecular interaction between a distal (DCRD) and a proximal regulatory domain (PCRD) within the C terminus of long Cav1.3 L-type Ca2+ channels (Cav1.3L) is a major determinant of their voltage- and Ca2+-dependent gating kinetics. Removal of these regulatory domains by alternative splicing generates Cav1.342A channels that activate at a more negative voltage range and exhibit more pronounced Ca2+-dependent inactivation. Here we describe the discovery of a novel short splice variant (Cav1.343S) that is expressed at high levels in the brain but not in the heart. It lacks the DCRD but, in contrast to Cav1.342A, still contains PCRD. When expressed together with α2δ1 and β3 subunits in tsA-201 cells, Cav1.343S also activated at more negative voltages like Cav1.342A but Ca2+-dependent inactivation was less pronounced. Single channel recordings revealed much higher channel open probabilities for both short splice variants as compared with Cav1.3L. The presence of the proximal C terminus in Cav1.343S channels preserved their modulation by distal C terminus-containing Cav1.3- and Cav1.2-derived C-terminal peptides. Removal of the C-terminal modulation by alternative splicing also induced a faster decay of Ca2+ influx during electrical activities mimicking trains of neuronal action potentials. Our findings extend the spectrum of functionally diverse Cav1.3 L-type channels produced by tissue-specific alternative splicing. This diversity may help to fine tune Ca2+ channel signaling and, in the case of short variants lacking a functional C-terminal modulation, prevent excessive Ca2+ accumulation during burst firing in neurons. This may be especially important in neurons that are affected by Ca2+-induced neurodegenerative processes. PMID:21998310

A novel CaV2.2 channel inhibition by piracetam in peripheral and central neurons.

PubMed

Bravo-Martínez, Jorge; Arenas, Isabel; Vivas, Oscar; Rebolledo-Antúnez, Santiago; Vázquez-García, Mario; Larrazolo, Arturo; García, David E

2012-10-01

No mechanistic actions for piracetam have been documented to support its nootropic effects. Voltage-gated calcium channels have been proposed as a promising pharmacological target of nootropic drugs. In this study, we investigated the effect of piracetam on Ca(V)2.2 channels in peripheral neurons, using patch-clamp recordings from cultured superior cervical ganglion neurons. In addition, we tested if Ca(V)2.2 channel inhibition could be related with the effects of piracetam on central neurons. We found that piracetam inhibited native Ca(V)2.2 channels in superior cervical ganglion neurons in a dose-dependent manner, with an IC(50) of 3.4 μmol/L and a Hill coefficient of 1.1. GDPβS dialysis did not prevent piracetam-induced inhibition of Ca(V)2.2 channels and G-protein-coupled receptor activation by noradrenaline did not occlude the piracetam effect. Piracetam altered the biophysical characteristics of Ca(V)2.2 channel such as facilitation ratio. In hippocampal slices, piracetam and ω-conotoxin GVIA diminished the frequency of excitatory postsynaptic potentials and action potentials. Our results provide evidence of piracetam's actions on Ca(V)2.2 channels in peripheral neurons, which might explain some of its nootropic effects in central neurons.

G protein modulation of CaV2 voltage-gated calcium channels.

PubMed

Currie, Kevin P M

2010-01-01

Voltage-gated Ca(2+) channels translate the electrical inputs of excitable cells into biochemical outputs by controlling influx of the ubiquitous second messenger Ca(2+) . As such the channels play pivotal roles in many cellular functions including the triggering of neurotransmitter and hormone release by CaV2.1 (P/Q-type) and CaV2.2 (N-type) channels. It is well established that G protein coupled receptors (GPCRs) orchestrate precise regulation neurotransmitter and hormone release through inhibition of CaV2 channels. Although the GPCRs recruit a number of different pathways, perhaps the most prominent, and certainly most studied among these is the so-called voltage-dependent inhibition mediated by direct binding of Gβγ to the α1 subunit of CaV2 channels. This article will review the basics of Ca(2+) -channels and G protein signaling, and the functional impact of this now classical inhibitory mechanism on channel function. It will also provide an update on more recent developments in the field, both related to functional effects and crosstalk with other signaling pathways, and advances made toward understanding the molecular interactions that underlie binding of Gβγ to the channel and the voltage-dependence that is a signature characteristic of this mechanism.

Proceedings of the Non-Linear Aero Prediction Requirements Workshop

NASA Technical Reports Server (NTRS)

Logan, Michael J. (Editor)

1994-01-01

The purpose of the Non-Linear Aero Prediction Requirements Workshop, held at NASA Langley Research Center on 8-9 Dec. 1993, was to identify and articulate requirements for non-linear aero prediction capabilities during conceptual/preliminary design. The attendees included engineers from industry, government, and academia in a variety of aerospace disciplines, such as advanced design, aerodynamic performance analysis, aero methods development, flight controls, and experimental and theoretical aerodynamics. Presentations by industry and government organizations were followed by panel discussions. This report contains copies of the presentations and the results of the panel discussions.

C-terminal modulatory domain controls coupling of voltage-sensing to pore opening in Cav1.3 L-type Ca(2+) channels.

PubMed

Lieb, Andreas; Ortner, Nadine; Striessnig, Jörg

2014-04-01

Activity of voltage-gated Cav1.3 L-type Ca(2+) channels is required for proper hearing as well as sinoatrial node and brain function. This critically depends on their negative activation voltage range, which is further fine-tuned by alternative splicing. Shorter variants miss a C-terminal regulatory domain (CTM), which allows them to activate at even more negative potentials than C-terminally long-splice variants. It is at present unclear whether this is due to an increased voltage sensitivity of the Cav1.3 voltage-sensing domain, or an enhanced coupling of voltage-sensor conformational changes to the subsequent opening of the activation gate. We studied the voltage-dependence of voltage-sensor charge movement (QON-V) and of current activation (ICa-V) of the long (Cav1.3L) and a short Cav1.3 splice variant (Cav1.342A) expressed in tsA-201 cells using whole cell patch-clamp. Charge movement (QON) of Cav1.3L displayed a much steeper voltage-dependence and a more negative half-maximal activation voltage than Cav1.2 and Cav3.1. However, a significantly higher fraction of the total charge had to move for activation of Cav1.3 half-maximal conductance (Cav1.3: 68%; Cav1.2: 52%; Cav3.1: 22%). This indicated a weaker coupling of Cav1.3 voltage-sensor charge movement to pore opening. However, the coupling efficiency was strengthened in the absence of the CTM in Cav1.342A, thereby shifting ICa-V by 7.2 mV to potentials that were more negative without changing QON-V. We independently show that the presence of intracellular organic cations (such as n-methyl-D-glucamine) induces a pronounced negative shift of QON-V and a more negative activation of ICa-V of all three channels. These findings illustrate that the voltage sensors of Cav1.3 channels respond more sensitively to depolarization than those of Cav1.2 or Cav3.1. Weak coupling of voltage sensing to pore opening is enhanced in the absence of the CTM, allowing short Cav1.342A splice variants to activate at lower voltages

Silencing of the Cav3.2 T-type calcium channel gene in sensory neurons demonstrates its major role in nociception.

PubMed

Bourinet, Emmanuel; Alloui, Abdelkrim; Monteil, Arnaud; Barrère, Christian; Couette, Brigitte; Poirot, Olivier; Pages, Anne; McRory, John; Snutch, Terrance P; Eschalier, Alain; Nargeot, Joël

2005-01-26

Analgesic therapies are still limited and sometimes poorly effective, therefore finding new targets for the development of innovative drugs is urgently needed. In order to validate the potential utility of blocking T-type calcium channels to reduce nociception, we explored the effects of intrathecally administered oligodeoxynucleotide antisenses, specific to the recently identified T-type calcium channel family (CaV3.1, CaV3.2, and CaV3.3), on reactions to noxious stimuli in healthy and mononeuropathic rats. Our results demonstrate that the antisense targeting CaV3.2 induced a knockdown of the CaV3.2 mRNA and protein expression as well as a large reduction of 'CaV3.2-like' T-type currents in nociceptive dorsal root ganglion neurons. Concomitantly, the antisense treatment resulted in major antinociceptive, anti-hyperalgesic, and anti-allodynic effects, suggesting that CaV3.2 plays a major pronociceptive role in acute and chronic pain states. Taken together, the results provide direct evidence linking CaV3.2 T-type channels to pain perception and suggest that CaV3.2 may offer a specific molecular target for the treatment of pain.

Mechanism of auxiliary β-subunit-mediated membrane targeting of L-type (CaV1.2) channels

PubMed Central

Fang, Kun; Colecraft, Henry M

2011-01-01

Abstract Ca2+ influx via CaV1/CaV2 channels drives processes ranging from neurotransmission to muscle contraction. Association of a pore-forming α1 and cytosolic β is necessary for trafficking CaV1/CaV2 channels to the cell surface through poorly understood mechanisms. A prevalent idea suggests β binds the α1 intracellular I–II loop, masking an endoplasmic reticulum (ER) retention signal as the dominant mechanism for CaV1/CaV2 channel membrane trafficking. There are hints that other α1 subunit cytoplasmic domains may play a significant role, but the nature of their potential contribution is unclear. We assessed the roles of all intracellular domains of CaV1.2-α1C by generating chimeras featuring substitutions of all possible permutations of intracellular loops/termini of α1C into the β-independent CaV3.1-α1G channel. Surprisingly, functional analyses demonstrated α1C I–II loop strongly increases channel surface density while other cytoplasmic domains had a competing opposing effect. Alanine-scanning mutagenesis identified an acidic-residue putative ER export motif responsible for the I–II loop-mediated increase in channel surface density. β-dependent increase in current arose as an emergent property requiring four α1C intracellular domains, with the I–II loop and C-terminus being essential. The results suggest β binding to the α1C I–II loop causes a C-terminus-dependent rearrangement of intracellular domains, shifting a balance of power between export signals on the I–II loop and retention signals elsewhere. PMID:21746784

Optimization of Return Trajectories for Orbital Transfer Vehicle between Earth and Moon

NASA Technical Reports Server (NTRS)

Funase, Ryu; Tsuda, Yuichi; Kawaguchi, Jun'ichiro

2007-01-01

In this paper, optimum trajectories in Earth Transfer Orbit (ETO) for a lunar transportation system are proposed. This paper aims at improving the payload ratio of the reusable orbital transfer vehicle (OTV), which transports the payload from Low Earth Orbit (LEO) to Lunar Low Orbit (LLO) and returns to LEO. In ETO, we discuss ballistic flight using chemical propulsion, multi-impulse flight using electrical propulsion, and aero-assisted flight using aero-brake. The feasibility of the OTV is considered.

Integrated Aero-Propulsion CFD Methodology for the Hyper-X Flight Experiment

NASA Technical Reports Server (NTRS)

Cockrell, Charles E., Jr.; Engelund, Walter C.; Bittner, Robert D.; Dilley, Arthur D.; Jentink, Tom N.; Frendi, Abdelkader

2000-01-01

Computational fluid dynamics (CFD) tools have been used extensively in the analysis and development of the X-43A Hyper-X Research Vehicle (HXRV). A significant element of this analysis is the prediction of integrated vehicle aero-propulsive performance, which includes an integration of aerodynamic and propulsion flow fields. This paper describes analysis tools used and the methodology for obtaining pre-flight predictions of longitudinal performance increments. The use of higher-fidelity methods to examine flow-field characteristics and scramjet flowpath component performance is also discussed. Limited comparisons with available ground test data are shown to illustrate the approach used to calibrate methods and assess solution accuracy. Inviscid calculations to evaluate lateral-directional stability characteristics are discussed. The methodology behind 3D tip-to-tail calculations is described and the impact of 3D exhaust plume expansion in the afterbody region is illustrated. Finally, future technology development needs in the area of hypersonic propulsion-airframe integration analysis are discussed.

The Physics of Boundary-Layer Aero-Optic Effects

DTIC Science & Technology

2012-09-01

various models to predict aero-optical effects for both subsonic and supersonic Mach numbers, laser beam sizes and non- adiabatic walls. The developed...models to predict aero-optical effects for both subsonic and supersonic Mach numbers, laser beam sizes and non- adiabatic walls. The developed models were... Supersonic Facilities .................................................................................................... 8 3.3 2-D Wavefront Data

Progress in the structural understanding of voltage-gated calcium channel (CaV) function and modulation.

PubMed

Minor, Daniel L; Findeisen, Felix

2010-01-01

Voltage-gated calcium channels (CaVs) are large, transmembrane multiprotein complexes that couple membrane depolarization to cellular calcium entry. These channels are central to cardiac action potential propagation, neurotransmitter and hormone release, muscle contraction, and calcium-dependent gene transcription. Over the past six years, the advent of high-resolution structural studies of CaV components from different isoforms and CaV modulators has begun to reveal the architecture that underlies the exceptionally rich feedback modulation that controls CaV action. These descriptions of CaV molecular anatomy have provided new, structure-based insights into the mechanisms by which particular channel elements affect voltage-dependent inactivation (VDI), calcium‑dependent inactivation (CDI), and calcium‑dependent facilitation (CDF). The initial successes have been achieved through structural studies of soluble channel domains and modulator proteins and have proven most powerful when paired with biochemical and functional studies that validate ideas inspired by the structures. Here, we review the progress in this growing area and highlight some key open challenges for future efforts.

Progress in the structural understanding of voltage-gated calcium channel (CaV) function and modulation

PubMed Central

Findeisen, Felix

2010-01-01

Voltage-gated calcium channels (CaVs) are large, transmembrane multiprotein complexes that couple membrane depolarization to cellular calcium entry. These channels are central to cardiac action potential propagation, neurotransmitter and hormone release, muscle contraction and calcium-dependent gene transcription. Over the past six years, the advent of high-resolution structural studies of CaV components from different isoforms and CaV modulators has begun to reveal the architecture that underlies the exceptionally rich feedback modulation that controls CaV action. These descriptions of CaV molecular anatomy have provided new, structure-based insights into the mechanisms by which particular channel elements affect voltage-dependent inactivation (VDI), calcium-dependent inactivation (CDI) and calcium-dependent facilitation (CDF). The initial successes have been achieved through structural studies of soluble channel domains and modulator proteins and have proven most powerful when paired with biochemical and functional studies that validate ideas inspired by the structures. Here, we review the progress in this growing area and highlight some key open challenges for future efforts. PMID:21139419

Functional properties of a newly identified C-terminal splice variant of Cav1.3 L-type Ca2+ channels.

PubMed

Bock, Gabriella; Gebhart, Mathias; Scharinger, Anja; Jangsangthong, Wanchana; Busquet, Perrine; Poggiani, Chiara; Sartori, Simone; Mangoni, Matteo E; Sinnegger-Brauns, Martina J; Herzig, Stefan; Striessnig, Jörg; Koschak, Alexandra

2011-12-09

An intramolecular interaction between a distal (DCRD) and a proximal regulatory domain (PCRD) within the C terminus of long Ca(v)1.3 L-type Ca(2+) channels (Ca(v)1.3(L)) is a major determinant of their voltage- and Ca(2+)-dependent gating kinetics. Removal of these regulatory domains by alternative splicing generates Ca(v)1.3(42A) channels that activate at a more negative voltage range and exhibit more pronounced Ca(2+)-dependent inactivation. Here we describe the discovery of a novel short splice variant (Ca(v)1.3(43S)) that is expressed at high levels in the brain but not in the heart. It lacks the DCRD but, in contrast to Ca(v)1.3(42A), still contains PCRD. When expressed together with α2δ1 and β3 subunits in tsA-201 cells, Ca(v)1.3(43S) also activated at more negative voltages like Ca(v)1.3(42A) but Ca(2+)-dependent inactivation was less pronounced. Single channel recordings revealed much higher channel open probabilities for both short splice variants as compared with Ca(v)1.3(L). The presence of the proximal C terminus in Ca(v)1.3(43S) channels preserved their modulation by distal C terminus-containing Ca(v)1.3- and Ca(v)1.2-derived C-terminal peptides. Removal of the C-terminal modulation by alternative splicing also induced a faster decay of Ca(2+) influx during electrical activities mimicking trains of neuronal action potentials. Our findings extend the spectrum of functionally diverse Ca(v)1.3 L-type channels produced by tissue-specific alternative splicing. This diversity may help to fine tune Ca(2+) channel signaling and, in the case of short variants lacking a functional C-terminal modulation, prevent excessive Ca(2+) accumulation during burst firing in neurons. This may be especially important in neurons that are affected by Ca(2+)-induced neurodegenerative processes.

Estimating Energy Efficiency of Connected and Autonomous Vehicles in a Mixed Fleet

DOT National Transportation Integrated Search

2018-05-01

Jing Dong (orcid.org/0000-0002-7304-8430); Liang Hu (orcid.org/0000-0001-6351-8542); Chaoru Lu (orcid.org/0000-0001-8418-7658); Connected and autonomous vehicle (CAV) technologies are likely to be gradually implemented over time and in a traffic envi...

Technology requirements and readiness for very large vehicles

NASA Technical Reports Server (NTRS)

Conner, D. W.

1979-01-01

Common concerns of very large vehicles in the areas of economics, transportation system interfaces and operational problems were reviewed regarding their influence on vehicle configurations and technology. Fifty-four technology requirements were identified which are judged to be unique, or particularly critical, to very large vehicles. The requirements were about equally divided among the four general areas of aero/hydrodynamics, propulsion and acoustics, structures, and vehicle systems and operations. The state of technology readiness was judged to be poor to fair for slightly more than one half of the requirements. In the classic disciplinary areas, the state of technology readiness appears to be more advanced than for vehicle systems and operations.

76 FR 71246 - Airworthiness Directives; Piaggio Aero Industries S.p.A. Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-17

... Airworthiness Directives; Piaggio Aero Industries S.p.A. Airplanes AGENCY: Federal Aviation Administration (FAA... directive (AD) for Piaggio Aero Industries S.p.A. Model P-180 airplanes. This AD results from mandatory.... For service information identified in this AD, contact Piaggio Aero Industries S.p.A. Airworthiness...

Aeronautical Satellite-Assisted Process for Information Exchange Through Network Technologies (Aero-SAPIENT) Conducted

NASA Technical Reports Server (NTRS)

Zernic, Michael J.

2002-01-01

Broadband satellite communications for aeronautics marries communication and network technologies to address NASA's goals in information technology base research and development, thereby serving the safety and capacity needs of the National Airspace System. This marriage of technology increases the interactivity between airborne vehicles and ground systems. It improves decision-making and efficiency, reduces operation costs, and improves the safety and capacity of the National Airspace System. To this end, a collaborative project called the Aeronautical Satellite Assisted Process for Information Exchange through Network Technologies, or Aero-SAPIENT, was conducted out of Tinker AFB, Oklahoma, during November and December 2000.

Altered thalamocortical rhythmicity and connectivity in mice lacking CaV3.1 T-type Ca2+ channels in unconsciousness

PubMed Central

Choi, Soonwook; Yu, Eunah; Lee, Seongwon; Llinás, Rodolfo R.

2015-01-01

In unconscious status (e.g., deep sleep and anesthetic unconsciousness) where cognitive functions are not generated there is still a significant level of brain activity present. Indeed, the electrophysiology of the unconscious brain is characterized by well-defined thalamocortical rhythmicity. Here we address the ionic basis for such thalamocortical rhythms during unconsciousness. In particular, we address the role of CaV3.1 T-type Ca2+ channels, which are richly expressed in thalamic neurons. Toward this aim, we examined the electrophysiological and behavioral phenotypes of mice lacking CaV3.1 channels (CaV3.1 knockout) during unconsciousness induced by ketamine or ethanol administration. Our findings indicate that CaV3.1 KO mice displayed attenuated low-frequency oscillations in thalamocortical loops, especially in the 1- to 4-Hz delta band, compared with control mice (CaV3.1 WT). Intriguingly, we also found that CaV3.1 KO mice exhibited augmented high-frequency oscillations during unconsciousness. In a behavioral measure of unconsciousness dynamics, CaV3.1 KO mice took longer to fall into the unconscious state than controls. In addition, such unconscious events had a shorter duration than those of control mice. The thalamocortical interaction level between mediodorsal thalamus and frontal cortex in CaV3.1 KO mice was significantly lower, especially for delta band oscillations, compared with that of CaV3.1 WT mice, during unconsciousness. These results suggest that the CaV3.1 channel is required for the generation of a given set of thalamocortical rhythms during unconsciousness. Further, that thalamocortical resonant neuronal activity supported by this channel is important for the control of vigilance states. PMID:26056284

Altered thalamocortical rhythmicity and connectivity in mice lacking CaV3.1 T-type Ca2+ channels in unconsciousness.

PubMed

Choi, Soonwook; Yu, Eunah; Lee, Seongwon; Llinás, Rodolfo R

2015-06-23

In unconscious status (e.g., deep sleep and anesthetic unconsciousness) where cognitive functions are not generated there is still a significant level of brain activity present. Indeed, the electrophysiology of the unconscious brain is characterized by well-defined thalamocortical rhythmicity. Here we address the ionic basis for such thalamocortical rhythms during unconsciousness. In particular, we address the role of CaV3.1 T-type Ca(2+) channels, which are richly expressed in thalamic neurons. Toward this aim, we examined the electrophysiological and behavioral phenotypes of mice lacking CaV3.1 channels (CaV3.1 knockout) during unconsciousness induced by ketamine or ethanol administration. Our findings indicate that CaV3.1 KO mice displayed attenuated low-frequency oscillations in thalamocortical loops, especially in the 1- to 4-Hz delta band, compared with control mice (CaV3.1 WT). Intriguingly, we also found that CaV3.1 KO mice exhibited augmented high-frequency oscillations during unconsciousness. In a behavioral measure of unconsciousness dynamics, CaV3.1 KO mice took longer to fall into the unconscious state than controls. In addition, such unconscious events had a shorter duration than those of control mice. The thalamocortical interaction level between mediodorsal thalamus and frontal cortex in CaV3.1 KO mice was significantly lower, especially for delta band oscillations, compared with that of CaV3.1 WT mice, during unconsciousness. These results suggest that the CaV3.1 channel is required for the generation of a given set of thalamocortical rhythms during unconsciousness. Further, that thalamocortical resonant neuronal activity supported by this channel is important for the control of vigilance states.

SIERRA/Aero Theory Manual Version 4.46.

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

Sierra Thermal/Fluid Team

2017-09-01

SIERRA/Aero is a two and three dimensional, node-centered, edge-based finite volume code that approximates the compressible Navier-Stokes equations on unstructured meshes. It is applicable to inviscid and high Reynolds number laminar and turbulent flows. Currently, two classes of turbulence models are provided: Reynolds Averaged Navier-Stokes (RANS) and hybrid methods such as Detached Eddy Simulation (DES). Large Eddy Simulation (LES) models are currently under development. The gas may be modeled either as ideal, or as a non-equilibrium, chemically reacting mixture of ideal gases. This document describes the mathematical models contained in the code, as well as certain implementation details. First, themore » governing equations are presented, followed by a description of the spatial discretization. Next, the time discretization is described, and finally the boundary conditions. Throughout the document, SIERRA/ Aero is referred to simply as Aero for brevity.« less

SIERRA/Aero Theory Manual Version 4.44

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

Sierra Thermal /Fluid Team

2017-04-01

SIERRA/Aero is a two and three dimensional, node-centered, edge-based finite volume code that approximates the compressible Navier-Stokes equations on unstructured meshes. It is applicable to inviscid and high Reynolds number laminar and turbulent flows. Currently, two classes of turbulence models are provided: Reynolds Averaged Navier-Stokes (RANS) and hybrid methods such as Detached Eddy Simulation (DES). Large Eddy Simulation (LES) models are currently under development. The gas may be modeled either as ideal, or as a non-equilibrium, chemically reacting mixture of ideal gases. This document describes the mathematical models contained in the code, as well as certain implementation details. First, themore » governing equations are presented, followed by a description of the spatial discretization. Next, the time discretization is described, and finally the boundary conditions. Throughout the document, SIERRA/ Aero is referred to simply as Aero for brevity.« less

Increased Ca2+ signaling through CaV1.2 promotes bone formation and prevents estrogen deficiency–induced bone loss

PubMed Central

Cao, Chike; Barnett, Adam S.; Mirando, Anthony J.; Rouse, Douglas; Mun, Se Hwan; Park-Min, Kyung-Hyun; McNulty, Amy L.; Karner, Courtney M.; Hilton, Matthew J.

2017-01-01

While the prevalence of osteoporosis is growing rapidly with population aging, therapeutic options remain limited. Here, we identify potentially novel roles for CaV1.2 L-type voltage–gated Ca2+ channels in osteogenesis and exploit a transgenic gain-of-function mutant CaV1.2 to stem bone loss in ovariectomized female mice. We show that endogenous CaV1.2 is expressed in developing bone within proliferating chondrocytes and osteoblasts. Using primary BM stromal cell (BMSC) cultures, we found that Ca2+ influx through CaV1.2 activates osteogenic transcriptional programs and promotes mineralization. We used Prx1-, Col2a1-, or Col1a1-Cre drivers to express an inactivation-deficient CaV1.2 mutant in chondrogenic and/or osteogenic precursors in vivo and found that the resulting increased Ca2+ influx markedly thickened bone not only by promoting osteogenesis, but also by inhibiting osteoclast activity through increased osteoprotegerin secretion from osteoblasts. Activating the CaV1.2 mutant in osteoblasts at the time of ovariectomy stemmed bone loss. Together, these data highlight roles for CaV1.2 in bone and demonstrate the potential dual anabolic and anticatabolic therapeutic actions of tissue-specific CaV1.2 activation in osteoblasts. PMID:29202453

Increased Ca2+ signaling through CaV1.2 promotes bone formation and prevents estrogen deficiency-induced bone loss.

PubMed

Cao, Chike; Ren, Yinshi; Barnett, Adam S; Mirando, Anthony J; Rouse, Douglas; Mun, Se Hwan; Park-Min, Kyung-Hyun; McNulty, Amy L; Guilak, Farshid; Karner, Courtney M; Hilton, Matthew J; Pitt, Geoffrey S

2017-11-16

While the prevalence of osteoporosis is growing rapidly with population aging, therapeutic options remain limited. Here, we identify potentially novel roles for CaV1.2 L-type voltage-gated Ca2+ channels in osteogenesis and exploit a transgenic gain-of-function mutant CaV1.2 to stem bone loss in ovariectomized female mice. We show that endogenous CaV1.2 is expressed in developing bone within proliferating chondrocytes and osteoblasts. Using primary BM stromal cell (BMSC) cultures, we found that Ca2+ influx through CaV1.2 activates osteogenic transcriptional programs and promotes mineralization. We used Prx1-, Col2a1-, or Col1a1-Cre drivers to express an inactivation-deficient CaV1.2 mutant in chondrogenic and/or osteogenic precursors in vivo and found that the resulting increased Ca2+ influx markedly thickened bone not only by promoting osteogenesis, but also by inhibiting osteoclast activity through increased osteoprotegerin secretion from osteoblasts. Activating the CaV1.2 mutant in osteoblasts at the time of ovariectomy stemmed bone loss. Together, these data highlight roles for CaV1.2 in bone and demonstrate the potential dual anabolic and anticatabolic therapeutic actions of tissue-specific CaV1.2 activation in osteoblasts.

Nonlinear Dynamic Modeling of a Supersonic Commercial Transport Turbo-Machinery Propulsion System for Aero-Propulso-Servo-Elasticity Research

NASA Technical Reports Server (NTRS)

Connolly, Joseph W.; Kopasakis, George; Carlson, Jan-Renee; Woolwine, Kyle

2015-01-01

This paper covers the development of an integrated nonlinear dynamic model for a variable cycle turbofan engine, supersonic inlet, and convergent-divergent nozzle that can be integrated with an aeroelastic vehicle model to create an overall Aero-Propulso-Servo-Elastic (APSE) modeling tool. The primary focus of this study is to provide a means to capture relevant thrust dynamics of a full supersonic propulsion system by using relatively simple quasi-one dimensional computational fluid dynamics (CFD) methods that will allow for accurate control algorithm development and capture the key aspects of the thrust to feed into an APSE model. Previously, propulsion system component models have been developed and are used for this study of the fully integrated propulsion system. An overview of the methodology is presented for the modeling of each propulsion component, with a focus on its associated coupling for the overall model. To conduct APSE studies the de- scribed dynamic propulsion system model is integrated into a high fidelity CFD model of the full vehicle capable of conducting aero-elastic studies. Dynamic thrust analysis for the quasi-one dimensional dynamic propulsion system model is presented along with an initial three dimensional flow field model of the engine integrated into a supersonic commercial transport.

Nonlinear Dynamic Modeling of a Supersonic Commercial Transport Turbo-Machinery Propulsion System for Aero-Propulso-Servo-Elasticity Research

NASA Technical Reports Server (NTRS)

Connolly, Joe; Carlson, Jan-Renee; Kopasakis, George; Woolwine, Kyle

2015-01-01

This paper covers the development of an integrated nonlinear dynamic model for a variable cycle turbofan engine, supersonic inlet, and convergent-divergent nozzle that can be integrated with an aeroelastic vehicle model to create an overall Aero-Propulso-Servo-Elastic (APSE) modeling tool. The primary focus of this study is to provide a means to capture relevant thrust dynamics of a full supersonic propulsion system by using relatively simple quasi-one dimensional computational fluid dynamics (CFD) methods that will allow for accurate control algorithm development and capture the key aspects of the thrust to feed into an APSE model. Previously, propulsion system component models have been developed and are used for this study of the fully integrated propulsion system. An overview of the methodology is presented for the modeling of each propulsion component, with a focus on its associated coupling for the overall model. To conduct APSE studies the described dynamic propulsion system model is integrated into a high fidelity CFD model of the full vehicle capable of conducting aero-elastic studies. Dynamic thrust analysis for the quasi-one dimensional dynamic propulsion system model is presented along with an initial three dimensional flow field model of the engine integrated into a supersonic commercial transport.

Volume Dynamics Propulsion System Modeling for Supersonics Vehicle Research

NASA Technical Reports Server (NTRS)

Kopasakis, George; Connolly, Joseph W.; Paxson, Daniel E.; Ma, Peter

2010-01-01

Under the NASA Fundamental Aeronautics Program the Supersonics Project is working to overcome the obstacles to supersonic commercial flight. The proposed vehicles are long slim body aircraft with pronounced aero-servo-elastic modes. These modes can potentially couple with propulsion system dynamics; leading to performance challenges such as aircraft ride quality and stability. Other disturbances upstream of the engine generated from atmospheric wind gusts, angle of attack, and yaw can have similar effects. In addition, for optimal propulsion system performance, normal inlet-engine operations are required to be closer to compressor stall and inlet unstart. To study these phenomena an integrated model is needed that includes both airframe structural dynamics as well as the propulsion system dynamics. This paper covers the propulsion system component volume dynamics modeling of a turbojet engine that will be used for an integrated vehicle Aero-Propulso-Servo-Elastic model and for propulsion efficiency studies.

Volume Dynamics Propulsion System Modeling for Supersonics Vehicle Research

NASA Technical Reports Server (NTRS)

Kopasakis, George; Connolly, Joseph W.; Paxson, Daniel E.; Ma, Peter

2008-01-01

Under the NASA Fundamental Aeronautics Program, the Supersonics Project is working to overcome the obstacles to supersonic commercial flight. The proposed vehicles are long slim body aircraft with pronounced aero-servo-elastic modes. These modes can potentially couple with propulsion system dynamics; leading to performance challenges such as aircraft ride quality and stability. Other disturbances upstream of the engine generated from atmospheric wind gusts, angle of attack, and yaw can have similar effects. In addition, for optimal propulsion system performance, normal inlet-engine operations are required to be closer to compressor stall and inlet unstart. To study these phenomena an integrated model is needed that includes both airframe structural dynamics as well as the propulsion system dynamics. This paper covers the propulsion system component volume dynamics modeling of a turbojet engine that will be used for an integrated vehicle Aero-Propulso-Servo-Elastic model and for propulsion efficiency studies.

Volume Dynamics Propulsion System Modeling for Supersonics Vehicle Research

NASA Technical Reports Server (NTRS)

Kopasakis, George; Connolly, Joseph W.; Paxson, Daniel E.; Ma, Peter

2008-01-01

Under the NASA Fundamental Aeronautics Program the Supersonics Project is working to overcome the obstacles to supersonic commercial flight. The proposed vehicles are long slim body aircraft with pronounced aero-servo-elastic modes. These modes can potentially couple with propulsion system dynamics; leading to performance challenges such as aircraft ride quality and stability. Other disturbances upstream of the engine generated from atmospheric wind gusts, angle of attack, and yaw can have similar effects. In addition, for optimal propulsion system performance, normal inlet-engine operations are required to be closer to compressor stall and inlet unstart. To study these phenomena an integrated model is needed that includes both airframe structural dynamics as well as the propulsion system dynamics. This paper covers the propulsion system component volume dynamics modeling of a turbojet engine that will be used for an integrated vehicle Aero- Propulso-Servo-Elastic model and for propulsion efficiency studies.

CaV1.3 L-type Ca2+ channels modulate depression-like behaviour in mice independent of deaf phenotype.

PubMed

Busquet, Perrine; Nguyen, Ngoc Khoi; Schmid, Eduard; Tanimoto, Naoyuki; Seeliger, Mathias W; Ben-Yosef, Tamar; Mizuno, Fengxia; Akopian, Abram; Striessnig, Jörg; Singewald, Nicolas

2010-05-01

Mounting evidence suggests that voltage-gated L-type Ca2+ channels can modulate affective behaviour. We therefore explored the role of CaV1.3 L-type Ca2+ channels in depression- and anxiety-like behaviours using CaV1.3-deficient mice (CaV1.3-/-). We showed that CaV1.3-/- mice displayed less immobility in the forced swim test as well as in the tail suspension test, indicating an antidepressant-like phenotype. Locomotor activity in the home cage or a novel open-field test was not influenced. In the elevated plus maze (EPM), CaV1.3-/- mice entered the open arms more frequently and spent more time there indicating an anxiolytic-like phenotype which was, however, not supported in the stress-induced hyperthermia test. By performing parallel experiments in Claudin 14 knockout mice (Cldn14-/-), which like CaV1.3-/- mice are congenitally deaf, an influence of deafness on the antidepressant-like phenotype could be ruled out. On the other hand, a similar EPM behaviour indicative of an anxiolytic phenotype was also found in the Cldn14-/- animals. Using electroretinography and visual behavioural tasks we demonstrated that at least in mice, CaV1.3 channels do not significantly contribute to visual function. However, marked morphological changes were revealed in synaptic ribbons in the outer plexiform layer of CaV1.3-/- retinas by immunohistochemistry suggesting a possible role of this channel type in structural plasticity at the ribbon synapse. Taken together, our findings indicate that CaV1.3 L-type Ca2+ channels modulate depression-like behaviour but are not essential for visual function. The findings raise the possibility that selective modulation of CaV1.3 channels could be a promising new therapeutic concept for the treatment of mood disorders.

Experimental investigation on aero-optics of supersonic turbulent boundary layers.

PubMed

Ding, Haolin; Yi, Shihe; Zhu, Yangzhu; He, Lin

2017-09-20

Nanoparticle-based planar laser scattering was used to measure the density distribution of the supersonic (Ma=3.0) turbulent boundary layer and the optical path difference (OPD), which is quite crucial for aero-optics study. Results were obtained using ray tracing. The influences of different layers in the boundary layer, turbulence scales, and light incident angle on aero-optics were examined, and the underlying flow physics were analyzed. The inner layer plays a dominant role, followed by the outer layer. One hundred OPD rms of the outer layer at different times satisfy the normal distribution better than that of the inner layer. Aero-optics induced by the outer layer is sensitive to the filter scale. When induced by the inner layer, it is not sensitive to the filter scale. The vortices with scales less than the Kolmogorov scale (=46.0  μm) have little influence on the aero-optics and could be ignored; the validity of the smallest optically active scale (=88.1  μm) proposed by Mani is verified, and vortices with scales less than that are ignored, resulting in a 1.62% decay of aero-optics; the filter with a width of 16-grid spacing (=182.4  μm) decreases OPD rms by 7.04%. With the increase of the angle between the wall-normal direction and the light-incident direction, the aero-optics becomes more serious, and the difference between the distribution of the OPD rms and the normal distribution increases. The difficulty of aero-optics correction is increased. Light tilted toward downstream experiences more distortions than when tilted toward upstream at the same angle relative to the wall-normal direction.

Dysregulation of Ca(v)1.4 channels disrupts the maturation of photoreceptor synaptic ribbons in congenital stationary night blindness type 2.

PubMed

Liu, Xiaoni; Kerov, Vasily; Haeseleer, Françoise; Majumder, Anurima; Artemyev, Nikolai; Baker, Sheila A; Lee, Amy

2013-01-01

Mutations in the gene encoding Cav 1.4, CACNA1F, are associated with visual disorders including X-linked incomplete congenital stationary night blindness type 2 (CSNB2). In mice lacking Cav 1.4 channels, there are defects in the development of "ribbon" synapses formed between photoreceptors (PRs) and second-order neurons. However, many CSNB2 mutations disrupt the function rather than expression of Cav 1.4 channels. Whether defects in PR synapse development due to altered Cav 1.4 function are common features contributing to the pathogenesis of CSNB2 is unknown. To resolve this issue, we profiled changes in the subcellular distribution of Cav 1.4 channels and synapse morphology during development in wild-type (WT) mice and mouse models of CSNB2. Using Cav 1.4-selective antibodies, we found that Cav 1.4 channels associate with ribbon precursors early in development and are concentrated at both rod and cone PR synapses in the mature retina. In mouse models of CSNB2 in which the voltage-dependence of Cav 1.4 activation is either enhanced (Cav 1.4I756T) or inhibited (CaBP4 KO), the initial stages of PR synaptic ribbon formation are largely unaffected. However, after postnatal day 13, many PR ribbons retain the immature morphology. This synaptic abnormality corresponds in severity to the defect in synaptic transmission in the adult mutant mice, suggesting that lack of sufficient mature synapses contributes to vision impairment in Cav 1.4I756T and CaBP4 KO mice. Our results demonstrate the importance of proper Cav 1.4 function for efficient PR synapse maturation, and that dysregulation of Cav 1.4 channels in CSNB2 may have synaptopathic consequences.

Inhibition of recombinant Ca(v)3.1 (alpha(1G)) T-type calcium channels by the antipsychotic drug clozapine.

PubMed

Choi, Kee-Hyun; Rhim, Hyewhon

2010-01-25

Low voltage-activated T-type calcium channels are involved in the regulation of the neuronal excitability, and could be subject to many antipsychotic drugs. The effects of clozapine, an atypical antipsychotic drug, on recombinant Ca(v)3.1 T-type calcium channels heterologously expressed in human embryonic kidney 293 cells were examined using whole-cell patch-clamp recordings. At a standard holding potential of -100 mV, clozapine inhibited Ca(v)3.1 currents with an IC(50) value of 23.7+/-1.3 microM in a use-dependent manner. However, 10 microM clozapine inhibited more than 50% of the Ca(v)3.1 currents in recordings at a more physiologically relevant holding potential of -75 mV. Clozapine caused a significant hyperpolarizing shift in the steady-state inactivation curve of the Ca(v)3.1 channels, which is presumably the main mechanism accounting for the inhibition of the Ca(v)3.1 currents. In addition, clozapine slowed Ca(v)3.1 deactivation and inactivation kinetics but not activation kinetics. Clozapine-induced changes in deactivation and inactivation rates of the Ca(v)3.1 channel gating would likely facilitate calcium influx via Ca(v)3.1 T-type calcium channels. Thus, clozapine may exert its therapeutic and/or side effects by altering cell's excitability and firing properties through actions on T-type calcium channels.

Stapled Voltage-Gated Calcium Channel (CaV) α-Interaction Domain (AID) Peptides Act As Selective Protein–Protein Interaction Inhibitors of CaV Function

PubMed Central

2017-01-01

For many voltage-gated ion channels (VGICs), creation of a properly functioning ion channel requires the formation of specific protein–protein interactions between the transmembrane pore-forming subunits and cystoplasmic accessory subunits. Despite the importance of such protein–protein interactions in VGIC function and assembly, their potential as sites for VGIC modulator development has been largely overlooked. Here, we develop meta-xylyl (m-xylyl) stapled peptides that target a prototypic VGIC high affinity protein–protein interaction, the interaction between the voltage-gated calcium channel (CaV) pore-forming subunit α-interaction domain (AID) and cytoplasmic β-subunit (CaVβ). We show using circular dichroism spectroscopy, X-ray crystallography, and isothermal titration calorimetry that the m-xylyl staples enhance AID helix formation are structurally compatible with native-like AID:CaVβ interactions and reduce the entropic penalty associated with AID binding to CaVβ. Importantly, electrophysiological studies reveal that stapled AID peptides act as effective inhibitors of the CaVα1:CaVβ interaction that modulate CaV function in an CaVβ isoform-selective manner. Together, our studies provide a proof-of-concept demonstration of the use of protein–protein interaction inhibitors to control VGIC function and point to strategies for improved AID-based CaV modulator design. PMID:28278376

TRANSCRIPTIONAL UPREGULATION OF α2δ-1 ELEVATES ARTERIAL SMOOTH MUSCLE CELL CAV1.2 CHANNEL SURFACE EXPRESSION AND CEREBROVASCULAR CONSTRICTION IN GENETIC HYPERTENSION

PubMed Central

Bannister, John P.; Bulley, Simon; Narayanan, Damodaran; Thomas-Gatewood, Candice; Luzny, Patrik; Pachuau, Judith; Jaggar, Jonathan H.

2012-01-01

A hallmark of hypertension is an increase in arterial myocyte voltage-dependent Ca2+ (CaV1.2) currents that induces pathological vasoconstriction. CaV1.2 channels are heteromeric complexes comprising a pore forming CaV1.2α1 with auxiliary α2δ and β subunits. Molecular mechanisms that elevate CaV1.2 currents during hypertension and the potential contribution of CaV1.2 auxiliary subunits are unclear. Here, we investigated the pathological significance of α2δ subunits in vasoconstriction associated with hypertension. Age-dependent development of hypertension in spontaneously hypertensive rats (SHR) was associated with an unequal elevation in α2δ-1 and CaV1.2α1 mRNA and protein in cerebral artery myocytes, with α2δ-1 increasing more than CaV1.2α1. Other α2δ isoforms did not emerge in hypertension. Myocytes and arteries of hypertensive SHR displayed higher surface-localized α2δ-1 and CaV1.2α1 proteins, surface α2δ-1 to CaV1.2α1 ratio (α2δ-1:CaV1.2α1), CaV1.2 current-density and non-inactivating current, and pressure- and - depolarization-induced vasoconstriction than those of Wistar-Kyoto controls. Pregabalin, an α2δ-1 ligand, did not alter α2δ-1 or CaV1.2α1 total protein, but normalized α2δ-1 and CaV1.2α1 surface expression, surface α2δ-1:CaV1.2α1, CaV1.2 current-density and inactivation, and vasoconstriction in myocytes and arteries of hypertensive rats to control levels. Genetic hypertension is associated with an elevation in α2δ-1 expression that promotes surface trafficking of CaV1.2 channels in cerebral artery myocytes. This leads to an increase in CaV1.2 current-density and a reduction in current inactivation that induces vasoconstriction. Data also suggest that α2δ-1 targeting is a novel strategy that may be used to reverse pathological CaV1.2 channel trafficking to induce cerebrovascular dilation in hypertension. PMID:22949532

Hypersonic airbreathing vehicle conceptual design (focus on aero-space plane)

NASA Technical Reports Server (NTRS)

Hunt, James L.; Martin, John G.

1989-01-01

The airbreathing single stage to orbit (SSTO) vehicle design environment is variable-rich, intricately networked and sensitivity intensive. As such, it represents a tremondous technology challenge. Creating a viable design will require sophisticated configuration/synthesis and the synergistic integration of advanced technologies across the discipline spectrum. In design exercises, reductions in the fuel weight-fraction requirements projected for an orbital vehicle concept can result from improvements in aerodynamics/controls, propulsion efficiencies and trajectory optimization; also, gains in the fuel weight-fraction achievable for such a concept can result from improvements in structural design, heat management techniques, and material properties. As these technology advances take place, closure on a viable vehicle design will be realizable.

Cav-1 deficiency promotes liver fibrosis in carbon tetrachloride (CCl4)-induced mice by regulation of oxidative stress and inflammation responses.

PubMed

Ji, De-Gang; Zhang, Yan; Yao, Song-Mei; Zhai, Xu-Jie; Zhang, Li-Rong; Zhang, Yao-Zhong; Li, Hui

2018-06-01

Caveolin-1 (Cav-1), as a membrane protein involved in the formation of caveolae, binds steroid receptors and endothelial nitric oxide synthase, limiting its translocation and activation. In the present study, we investigated the role of Cav-1 in the progression of hepatic fibrosis induced by carbon tetrachloride (CCl 4 ) in murine animals. Therefore, the wild type (WT) and Cav-1-knockout (Cav-1 -/- ) mice were used in our study and subjected to CCl 4 . The results indicated that CCl 4 induced the decrease of Cav-1 expression in liver tissue samples. And Cav-1 -/- intensified CCl 4 -triggered hepatic injury, evidenced by the stronger hepatic histological alterations, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and liver terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells. CCl 4 led to oxidative stress, supported by the reduced superoxide dismutase (SOD) activity and glutathione (GSH) levels, as well as enhanced malondialdehyde (MDA) and O 2 - levels in liver samples. And the process was intensified by Cav-1 -/- . Additionally, CCl 4 -caused hepatic inflammation was aggregated by Cav-1 -/- via further increasing the secretion of pro-inflammatory cytokines. Moreover, CCl 4 -caused fibrosis was strengthened by Cav-1 -/- , which was evidenced by the up-regulation of α-smooth muscle actin (α-SMA), collagen alpha 1 type 1 (Col1A1), lysyl oxidase (Lox) and transforming growth factor-β1 (TGF-β1) in liver tissues. Similar results were observed in TGF-β1-stimulated hepatic stellate cells (HSCs) and LX-2 cells without Cav-1 expressions that in vitro, suppressing Cav-1 further accelerated TGF-β1-induced oxidative stress, inflammation and fibrosis development. In conclusion, our results indicated that Cav-1 played an important role in CCl 4 -induced hepatic injury, which may be used as potential therapeutic target for hepatic fibrosis treatment. Copyright © 2018. Published by Elsevier Masson SAS.

Alterations of Ca(v)1.2 and 5-hydroxytryptamine in rat hearts after positional asphyxia.

PubMed

Li, X-F; Huang, Q-Y

2015-01-01

We investigated alterations of cardiac Ca(v)1.2 and 5-hydroxytryptamine (5-HT) associated with positional asphyxia. Male rats were divided into five groups: a control group with no restraint, group 1 restrained for 1 h, group 2 restrained for 2 h, group 3 restrained for 4 h, and group 4 restrained for 8 h. The rats that were restrained for 8 h ultimately suffered fatal asphyxia. After the restraint periods, the rats were sacrificed and immunohistochemistry was performed to evaluate the expressions of Ca(v)1.2 and 5-HT in the heart. Sections were analyzed by digital image analysis. Cardiac expression of Ca(v)1.2 and 5-HT proteins were significantly decreased by positional asphyxia in the rat, shown by integrated optical density (IOD) compared to controls. Our findings indicate that Ca(v)1.2 and 5-HT alterations could cause abnormal cardiac function, and the proteins investigated here may be useful for investigating the mechanisms underlying positional asphyxia.

Efficacy of predictive wavefront control for compensating aero-optical aberrations

NASA Astrophysics Data System (ADS)

Goorskey, David J.; Schmidt, Jason; Whiteley, Matthew R.

2013-07-01

Imaging and laser beam propagation from airborne platforms are degraded by dynamic aberrations due to air flow around the aircraft, aero-mechanical distortions and jitter, and free atmospheric turbulence. For certain applications, like dim-object imaging, free-space optical communications, and laser weapons, adaptive optics (AO) is necessary to compensate for the aberrations in real time. Aero-optical flow is a particularly interesting source of aberrations whose flowing structures can be exploited by adaptive and predictive AO controllers, thereby realizing significant performance gains. We analyze dynamic aero-optical wavefronts to determine the pointing angles at which predictive wavefront control is more effective than conventional, fixed-gain, linear-filter control. It was found that properties of the spatial decompositions and temporal statistics of the wavefronts are directly traceable to specific features in the air flow. Furthermore, the aero-optical wavefront aberrations at the side- and aft-looking angles were the most severe, but they also benefited the most from predictive AO.

Interference Analysis Status and Plans for Aeronautical Mobile Airport Communications System (AeroMACS)

NASA Technical Reports Server (NTRS)

Kerczewski, Robert J.; Wilson, Jeffrey D.

2010-01-01

Interference issues related to the operation of an aeronautical mobile airport communications system (AeroMACS) in the C-Band (specifically 5091-5150 MHz) is being investigated. The issue of primary interest is co-channel interference from AeroMACS into mobile-satellite system (MSS) feeder uplinks. The effort is focusing on establishing practical limits on AeroMACS transmissions from airports so that the threshold of interference into MSS is not exceeded. The analyses are being performed with the software package Visualyse Professional, developed by Transfinite Systems Limited. Results with omni-directional antennas and plans to extend the models to represent AeroMACS more accurately will be presented. These models should enable realistic analyses of emerging AeroMACS designs to be developed from NASA Test Bed, RTCA 223, and European results.

Splice isoform-specific suppression of the Cav2.1 variant underlying spinocerebellar ataxia type 6.

PubMed

Tsou, Wei-Ling; Soong, Bing-Wen; Paulson, Henry L; Rodríguez-Lebrón, Edgardo

2011-09-01

Spinocerebellar ataxia type 6 (SCA6) is an inherited neurodegenerative disease caused by a polyglutamine (polyQ) expansion in the Ca(V)2.1 voltage-gated calcium channel subunit (CACNA1A). There is currently no treatment for this debilitating disorder and thus a pressing need to develop preventative therapies. RNA interference (RNAi) has proven effective at halting disease progression in several models of spinocerebellar ataxia (SCA), including SCA types 1 and 3. However, in SCA6 and other dominantly inherited neurodegenerative disorders, RNAi-based strategies that selectively suppress expression of mutant alleles may be required. Using a Ca(V)2.1 mini-gene reporter system, we found that pathogenic CAG expansions in Ca(V)2.1 enhance splicing activity at the 3'end of the transcript, leading to a CAG repeat length-dependent increase in the levels of a polyQ-encoding Ca(V)2.1 mRNA splice isoform and the resultant disease protein. Taking advantage of this molecular phenomenon, we developed a novel splice isoform-specific (SIS)-RNAi strategy that selectively targets the polyQ-encoding Ca(V)2.1 splice variant. Selective suppression of transiently expressed and endogenous polyQ-encoding Ca(V)2.1 splice variants was achieved in a variety of cell-based models including a human neuronal cell line, using a new artificial miRNA-like delivery system. Moreover, the efficacy of gene silencing correlated with effective intracellular recognition and processing of SIS-RNAi miRNA mimics. These results lend support to the preclinical development of SIS-RNAi as a potential therapy for SCA6 and other dominantly inherited diseases. Copyright © 2011 Elsevier Inc. All rights reserved.

48 CFR 1852.235-70 - Center for AeroSpace Information.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Center for AeroSpace... SPACE ADMINISTRATION CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Texts of Provisions and Clauses 1852.235-70 Center for AeroSpace Information. As prescribed in 1835.070(a), insert the...

48 CFR 1852.235-70 - Center for AeroSpace Information.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Center for AeroSpace... SPACE ADMINISTRATION CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Texts of Provisions and Clauses 1852.235-70 Center for AeroSpace Information. As prescribed in 1835.070(a), insert the...

48 CFR 1852.235-70 - Center for AeroSpace Information.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Center for AeroSpace... SPACE ADMINISTRATION CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Texts of Provisions and Clauses 1852.235-70 Center for AeroSpace Information. As prescribed in 1835.070(a), insert the...

Aero dopes and varnishes

NASA Technical Reports Server (NTRS)

Britton, H T S

1927-01-01

Before proceeding to discuss the preparation of dope solutions, it will be necessary to consider some of the essential properties which should be possessed of a dope film, deposited in and on the surface of an aero fabric. The first is that it should tighten the material and second it should withstand weathering.

Aero-MINE (Motionless INtegrated Energy) for Distributed Scalable Wind Power.

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

Houchens, Brent C.; Blaylock, Myra L.

The proposed Aero-MINE technology will extract energy from wind without any exterior moving parts. Aero-MINEs can be integrated into buildings or function stand-alone, and are scalable. This gives them advantages similar to solar panels, but with the added benefit of operation in cloudy or dark conditions. Furthermore, compared to solar panels, Aero-MINEs can be manufactured at lower cost and with less environmental impact. Power generation is isolated internally by the pneumatic transmission of air and the outlet air-jet nozzles amplify the effectiveness. Multiple units can be connected to one centrally located electric generator. Aero-MINEs are ideal for the built-environment, withmore » numerous possible configurations ranging from architectural integration to modular bolt-on products. Traditional wind turbines suffer from many fundamental challenges. The fast-moving blades produce significant aero-acoustic noise, visual disturbances, light-induced flickering and impose wildlife mortality risks. The conversion of massive mechanical torque to electricity is a challenge for gears, generators and power conversion electronics. In addition, the installation, operation and maintenance of wind turbines is required at significant height. Furthermore, wind farms are often in remote locations far from dense regions of electricity customers. These technical and logistical challenges add significantly to the cost of the electricity produced by utility-scale wind farms. In contrast, distributed wind energy eliminates many of the logistical challenges. However, solutions such as micro-turbines produce relatively small amounts of energy due to the reduction in swept area and still suffer from the motion-related disadvantages of utility-scale turbines. Aero-MINEs combine the best features of distributed generation, while eliminating the disadvantages.« less

Distribution of calcium channel Ca(V)1.3 immunoreactivity in the rat spinal cord and brain stem.

PubMed

Sukiasyan, N; Hultborn, H; Zhang, M

2009-03-03

The function of local networks in the CNS depends upon both the connectivity between neurons and their intrinsic properties. An intrinsic property of spinal motoneurons is the presence of persistent inward currents (PICs), which are mediated by non-inactivating calcium (mainly Ca(V)1.3) and/or sodium channels and serve to amplify neuronal input signals. It is of fundamental importance for the prediction of network function to determine the distribution of neurons possessing the ion channels that produce PICs. Although the distribution pattern of Ca(V)1.3 immunoreactivity (Ca(V)1.3-IR) has been studied in some specific central nervous regions in some species, so far no systematic investigations have been performed in both the rat spinal cord and brain stem. In the present study this issue was investigated by immunohistochemistry. The results indicated that the Ca(V)1.3-IR neurons were widely distributed across different parts of the spinal cord and the brain stem although with variable labeling intensities. In the spinal gray matter large neurons in the ventral horn (presumably motoneurons) tended to display higher levels of immunoreactivity than smaller neurons in the dorsal horn. In the white matter, a subset of glial cells labeled by an oligodendrocyte marker was also Ca(V)1.3-positive. In the brain stem, neurons in the motor nuclei appeared to have higher levels of immunoreactivity than those in the sensory nuclei. Moreover, a number of nuclei containing monoaminergic cells, for example the locus coeruleus, were also strongly immunoreactive. Ca(V)1.3-IR was consistently detected in the neuronal perikarya regardless of the neuronal type. However, in the large neurons in the spinal ventral horn and the cranial motor nuclei the Ca(V)1.3-IR was clearly detectable in first and second order dendrites. These results indicate that in the rat spinal cord and brain stem Ca(V)1.3 is probably a common calcium channel used by many kinds of neurons to facilitate the neuronal

Adenosine triphosphate regulates the activity of guinea pig Cav1.2 channel by direct binding to the channel in a dose-dependent manner.

PubMed

Feng, Rui; Xu, Jianjun; Minobe, Etsuko; Kameyama, Asako; Yang, Lei; Yu, Lifeng; Hao, Liying; Kameyama, Masaki

2014-05-01

The present study is to investigate the mechanism by which ATP regulates Cav1.2 channel activity. Ventricular tissue was obtained from adult guinea pig hearts using collagenase. Ca(2+) channel activity was monitored using the patch-clamp technique. Proteins were purified using wheat germ agglutinin-Sepharose, and the concentration was determined using the Coomassie brilliant blue technique. ATP binding to the Cav1.2 channel was examined using the photoaffinity method. EDA-ATP-biotin maintains Ca(2+) channel activity in inside-out membrane patches. ATP directly bound to the Cav1.2 channel in a dose-dependent manner, and at least two molecules of ATP bound to one molecule of the Cav1.2 channel. Low levels of calmodulin (CaM) increased ATP binding to the Cav1.2 channel, but higher levels of CaM decreased ATP binding to the Cav1.2 channel. In addition, Ca(2+) was another regulator for ATP binding to the Cav1.2 channel. Furthermore, ATP bound to GST-fusion peptides of NH2-terminal region (amino acids 6-140) and proximal COOH-terminal region (amino acids 1,509-1,789) of the main subunit (α1C) of the Cav1.2 channel. Our data suggest that ATP might regulate Cav1.2 channel activity by directly binding to the Cav1.2 channel in a dose-dependent manner. In addition, the ATP-binding effect to the Cav1.2 channel was both CaM- and Ca(2+) dependent.

Dependence of AeroMACS Interference on Airport Radiation Pattern Characteristics

NASA Technical Reports Server (NTRS)

Wilson, Jeffrey D.

2012-01-01

AeroMACS (Aeronautical Mobile Airport Communications System), which is based upon the IEEE 802.16e mobile wireless standard, is expected to be implemented in the 5091 to 5150 MHz frequency band. As this band is also occupied by Mobile Satellite Service (MSS) feeder uplinks, AeroMACS must be designed to avoid interference with this incumbent service. The aspects of AeroMACS operation that present potential interference are under analysis in order to enable the definition of standards that assure that such interference will be avoided. In this study, the cumulative interference power distribution at low earth orbit from AeroMACS transmitters at the 497 major airports in the contiguous United States was simulated with the Visualyse Professional software. The dependence of the interference power on the number of antenna beams per airport, gain patterns, and beam direction orientations was simulated. As a function of these parameters, the simulation results are presented in terms of the limitations on transmitter power required to maintain the cumulative interference power under the established threshold.

Dependence of AeroMACS Interference on Airport Radiation Pattern Characteristics

NASA Technical Reports Server (NTRS)

Wilson, Jeffrey D.

2012-01-01

AeroMACS (Aeronautical Mobile Airport Communications System), which is based upon the IEEE 802.16e mobile wireless standard, is expected to be implemented in the 5091-5150 MHz frequency band. As this band is also occupied by Mobile Satellite Service (MSS) feeder uplinks, AeroMACS must be designed to avoid interference with this incumbent service. The aspects of AeroMACS operation that present potential interference are under analysis in order to enable the definition of standards that assure that such interference will be avoided. In this study, the cumulative interference power distribution at low earth orbit from AeroMACS transmitters at the 497 major airports in the contiguous United States was simulated with the Visualyse Professional software. The dependence of the interference power on the number of antenna beams per airport, gain patterns, and beam direction orientations was simulated. As a function of these parameters, the simulation results are presented in terms of the limitations on transmitter power required to maintain the cumulative interference power under the established threshold.

Genetic alteration of the metal/redox modulation of Cav3.2 T-type calcium channel reveals its role in neuronal excitability.

PubMed

Voisin, Tiphaine; Bourinet, Emmanuel; Lory, Philippe

2016-07-01

In this study, we describe a new knock-in (KI) mouse model that allows the study of the H191-dependent regulation of T-type Cav3.2 channels. Sensitivity to zinc, nickel and ascorbate of native Cav3.2 channels is significantly impeded in the dorsal root ganglion (DRG) neurons of this KI mouse. Importantly, we describe that this H191-dependent regulation has discrete but significant effects on the excitability properties of D-hair (down-hair) cells, a sub-population of DRG neurons in which Cav3.2 currents prominently regulate excitability. Overall, this study reveals that the native H191-dependent regulation of Cav3.2 channels plays a role in the excitability of Cav3.2-expressing neurons. This animal model will be valuable in addressing the potential in vivo roles of the trace metal and redox modulation of Cav3.2 T-type channels in a wide range of physiological and pathological conditions. Cav3.2 channels are T-type voltage-gated calcium channels that play important roles in controlling neuronal excitability, particularly in dorsal root ganglion (DRG) neurons where they are involved in touch and pain signalling. Cav3.2 channels are modulated by low concentrations of metal ions (nickel, zinc) and redox agents, which involves the histidine 191 (H191) in the channel's extracellular IS3-IS4 loop. It is hypothesized that this metal/redox modulation would contribute to the tuning of the excitability properties of DRG neurons. However, the precise role of this H191-dependent modulation of Cav3.2 channel remains unresolved. Towards this goal, we have generated a knock-in (KI) mouse carrying the mutation H191Q in the Cav3.2 protein. Electrophysiological studies were performed on a subpopulation of DRG neurons, the D-hair cells, which express large Cav3.2 currents. We describe an impaired sensitivity to zinc, nickel and ascorbate of the T-type current in D-hair neurons from KI mice. Analysis of the action potential and low-threshold calcium spike (LTCS) properties revealed

Pharmacoresistant Cav 2·3 (E-type/R-type) voltage-gated calcium channels influence heart rate dynamics and may contribute to cardiac impulse conduction.

PubMed

Galetin, Thomas; Tevoufouet, Etienne E; Sandmeyer, Jakob; Matthes, Jan; Nguemo, Filomain; Hescheler, Jürgen; Weiergräber, Marco; Schneider, Toni

2013-07-01

Voltage-gated Ca(2+) channels regulate cardiac automaticity, rhythmicity and excitation-contraction coupling. Whereas L-type (Cav 1·2, Cav 1·3) and T-type (Cav 3·1, Cav 3·2) channels are widely accepted for their functional relevance in the heart, the role of Cav 2·3 Ca(2+) channels expressing R-type currents remains to be elucidated. We have investigated heart rate dynamics in control and Cav 2·3-deficient mice using implantable electrocardiogram radiotelemetry and pharmacological injection experiments. Autonomic block revealed that the intrinsic heart rate does not differ between both genotypes. Systemic administration of isoproterenol resulted in a significant reduction in interbeat interval in both genotypes. It remained unaffected after administering propranolol in Cav 2·3(-|-) mice. Heart rate from isolated hearts as well as atrioventricular conduction for both genotypes differed significantly. Additionally, we identified and analysed the developmental expression of two splice variants, i.e. Cav 2·3c and Cav 2·3e. Using patch clamp technology, R-type currents could be detected in isolated prenatal cardiomyocytes and be related to R-type Ca(2+) channels. Our results indicate that on the systemic level, the pharmacologically inducible heart rate range and heart rate reserve are impaired in Cav 2·3 (-|-) mice. In addition, experiments on Langendorff perfused hearts elucidate differences in basic properties between both genotypes. Thus, Cav 2·3 does not only contribute to the cardiac autonomous nervous system but also to intrinsic rhythm propagation. Copyright © 2012 John Wiley & Sons, Ltd.

Splice isoform-specific suppression of the CaV2.1 variant underlying Spinocerebellar ataxia type 6

PubMed Central

Tsou, Wei-Ling; Soong, Bing-Wen; Paulson, Henry L.; Rodríguez-Lebrón, Edgardo

2011-01-01

Spinocerebellar ataxia type 6 (SCA6) is an inherited neurodegenerative disease caused by a polyglutamine (polyQ) expansion in the CaV2.1 voltage-gated calcium channel subunit (CACNA1A). There is currently no treatment for this debilitating disorder and thus a pressing need to develop preventative therapies. RNA interference (RNAi) has proven effective at halting disease progression in several models of spinocerebellar ataxia (SCA), including SCA types 1 and 3. However, in SCA6 and other dominantly inherited neurodegenerative disorders, RNAi-based strategies that selectively suppress expression of mutant alleles may be required. Using a CaV2.1 mini-gene reporter system, we found that pathogenic CAG expansions in CaV2.1 enhance splicing activity at the 3′end of the transcript, leading to a CAG repeat length-dependent increase in the levels of a polyQ-encoding CaV2.1 mRNA splice isoform and the resultant disease protein. Taking advantage of this molecular phenomenon, we developed a novel splice isoform-specific (SIS)-RNAi strategy that selectively targets the polyQ-encoding CaV2.1 splice variant. Selective suppression of transiently expressed and endogenous polyQ-encoding CaV2.1 splice variants was achieved in a variety of cell-based models including a human neuronal cell line, using a new artificial miRNA-like delivery system. Moreover, the efficacy of gene silencing correlated with effective intracellular recognition and processing of SIS-RNAi miRNA mimics. These results lend support to the preclinical development of SIS-RNAi as a potential therapy for SCA6 and other dominantly inherited diseases. PMID:21550405

Genetic variation at the microRNA binding site of CAV1 gene is associated with lung cancer susceptibility

PubMed Central

Fang, Xue; Li, Xuelian; Yin, Zhihua; Xia, Lingzi; Quan, Xiaowei; Zhao, Yuxia; Zhou, Baosen

2017-01-01

Single nucleotide polymorphism (SNP) may influence the genesis and development of cancer in a variety of ways depending on their location. Here we conducted a study in Chinese female non-smokers to investigate the relationship between rs1049337, rs926198 and the risk or survival of lung cancer. Further, we explored whether rs1049337 could alter the binding affinity between the mRNA of CAV1 and the corresponding microRNAs. Finally, we evaluated the relationship between expression level of CAV1 and prognosis of lung cancer. The results showed that the rs1049337-C allele and rs926198-C allele were the protective alleles of lung cancer risk. Haplotype analysis indicated that the C-C haplotype (constructed by rs1049337 and rs926198) was a protective haplotype for lung cancer risk. The result of luciferase reporter assay showed that rs1049337 can affect the binding affinity of CAV1 mRNA to the corresponding microRNAs both in A549 cell line and H1299 cell line. Compared with C allele, T allele had a relatively decreased luciferase activity. Compared with paired normal adjacent tissue or normal lung tissue, lung cancer tissue showed a relatively low level of CAV1. Refer to those patients at early stage of lung cancer, the expression level of CAV1 in patients at late stage of lung cancer was relatively low. In conclusion, the results indicated that rs1049337, it's a SNP located at 3′UTR region of CAV1 may affect lung cancer risk by altering the binding affinity between the mRNA of CAV1 and the corresponding microRNAs. PMID:29190968

Spatial-temporal-covariance-based modeling, analysis, and simulation of aero-optics wavefront aberrations.

PubMed

Vogel, Curtis R; Tyler, Glenn A; Wittich, Donald J

2014-07-01

We introduce a framework for modeling, analysis, and simulation of aero-optics wavefront aberrations that is based on spatial-temporal covariance matrices extracted from wavefront sensor measurements. Within this framework, we present a quasi-homogeneous structure function to analyze nonhomogeneous, mildly anisotropic spatial random processes, and we use this structure function to show that phase aberrations arising in aero-optics are, for an important range of operating parameters, locally Kolmogorov. This strongly suggests that the d5/3 power law for adaptive optics (AO) deformable mirror fitting error, where d denotes actuator separation, holds for certain important aero-optics scenarios. This framework also allows us to compute bounds on AO servo lag error and predictive control error. In addition, it provides us with the means to accurately simulate AO systems for the mitigation of aero-effects, and it may provide insight into underlying physical processes associated with turbulent flow. The techniques introduced here are demonstrated using data obtained from the Airborne Aero-Optics Laboratory.

Regulation of Neuronal Cav3.1 Channels by Cyclin-Dependent Kinase 5 (Cdk5)

PubMed Central

González-Ramírez, Ricardo; González-Billault, Christian; Felix, Ricardo

2015-01-01

Low voltage-activated (LVA) T-type Ca2+ channels activate in response to subthreshold membrane depolarizations and therefore represent an important source of Ca2+ influx near the resting membrane potential. In neurons, these proteins significantly contribute to control relevant physiological processes including neuronal excitability, pacemaking and post-inhibitory rebound burst firing. Three subtypes of T-type channels (Cav3.1 to Cav3.3) have been identified, and using functional expression of recombinant channels diverse studies have validated the notion that T-type Ca2+ channels can be modulated by various endogenous ligands as well as by second messenger pathways. In this context, the present study reveals a previously unrecognized role for cyclin-dependent kinase 5 (Cdk5) in the regulation of native T-type channels in N1E-115 neuroblastoma cells, as well as recombinant Cav3.1channels heterologously expressed in HEK-293 cells. Cdk5 and its co-activators play critical roles in the regulation of neuronal differentiation, cortical lamination, neuronal cell migration and axon outgrowth. Our results show that overexpression of Cdk5 causes a significant increase in whole cell patch clamp currents through T-type channels in N1E-115 cells, while siRNA knockdown of Cdk5 greatly reduced these currents. Consistent with this, overexpression of Cdk5 in HEK-293 cells stably expressing Cav3.1channels upregulates macroscopic currents. Furthermore, using site-directed mutagenesis we identified a major phosphorylation site at serine 2234 within the C-terminal region of the Cav3.1subunit. These results highlight a novel role for Cdk5 in the regulation of T-type Ca2+ channels. PMID:25760945

Regulation of neuronal cav3.1 channels by cyclin-dependent kinase 5 (Cdk5).

PubMed

Calderón-Rivera, Aida; Sandoval, Alejandro; González-Ramírez, Ricardo; González-Billault, Christian; Felix, Ricardo

2015-01-01

Low voltage-activated (LVA) T-type Ca2+ channels activate in response to subthreshold membrane depolarizations and therefore represent an important source of Ca2+ influx near the resting membrane potential. In neurons, these proteins significantly contribute to control relevant physiological processes including neuronal excitability, pacemaking and post-inhibitory rebound burst firing. Three subtypes of T-type channels (Cav3.1 to Cav3.3) have been identified, and using functional expression of recombinant channels diverse studies have validated the notion that T-type Ca2+ channels can be modulated by various endogenous ligands as well as by second messenger pathways. In this context, the present study reveals a previously unrecognized role for cyclin-dependent kinase 5 (Cdk5) in the regulation of native T-type channels in N1E-115 neuroblastoma cells, as well as recombinant Cav3.1channels heterologously expressed in HEK-293 cells. Cdk5 and its co-activators play critical roles in the regulation of neuronal differentiation, cortical lamination, neuronal cell migration and axon outgrowth. Our results show that overexpression of Cdk5 causes a significant increase in whole cell patch clamp currents through T-type channels in N1E-115 cells, while siRNA knockdown of Cdk5 greatly reduced these currents. Consistent with this, overexpression of Cdk5 in HEK-293 cells stably expressing Cav3.1channels upregulates macroscopic currents. Furthermore, using site-directed mutagenesis we identified a major phosphorylation site at serine 2234 within the C-terminal region of the Cav3.1subunit. These results highlight a novel role for Cdk5 in the regulation of T-type Ca2+ channels.

High glucose induces formation of tau hyperphosphorylation via Cav-1-mTOR pathway: A potential molecular mechanism for diabetes-induced cognitive dysfunction

PubMed Central

Wu, Jing; Zhou, Shan-Lei; Pi, Lin-Hua; Shi, Xia-Jie; Ma, Ling-Ran; Chen, Zi; Qu, Min-Li; Li, Xin; Nie, Sheng-Dan; Liao, Duan-Fang; Pei, Jin-Jing; Wang, Shan

2017-01-01

The abnormally hyperphosphorylated tau is thought to be implicated in diabetes-associated cognitive deficits. The role of mammalian target of rapamycin (mTOR) / S6 kinase (S6K) signalling in the formation of tau hyperphosphorylation has been previously studied. Caveolin-1 (Cav-1), the essential structure protein of caveolae, promotes neuronal survival and growth, and inhibits glucose metabolism. In this study, we aimed to investigate the role of Cav-1 in the formation of tau hyperphosphorylation under chronic hyperglycemic condition (HGC). Diabetic rats were induced by streptozotocin (STZ). Primary hippocampal neurons with or without molecular intervention such as the transient over-expression or knock-down were subjected to HGC. The obtained experimental samples were analyzed by real time quantitative RT-PCR, Western blot, immunofluorescence or immunohistochemisty. We found: 1) that a chronic HGC directly decreases Cav-1 expression, increases tau phosphorylation and activates mTOR/S6K signalling in the brain neurons of diabetic rats, 2) that overexpression of Cav-1 attenuates tau hyperphosphorylation induced by chronic HGC in primary hippocampal neurons, whereas down-regulation of Cav-1 using Cav-1 siRNA dramatically worsens tau hyperphosphorylation via mTOR/S6K signalling pathway, and 3) that the down-regulation of Cav-1 induced by HGC is independent of mTOR signalling. Our results suggest that tau hyperphosphorylation and the sustained over-activated mTOR signalling under hyperglycemia may be due to the suppression of Cav-1. Therefore, Cav-1 is a potential therapeutic target for diabetes-induced cognitive dysfunction. PMID:28489581

Modulation of voltage- and Ca2+-dependent gating of CaV1.3 L-type calcium channels by alternative splicing of a C-terminal regulatory domain.

PubMed

Singh, Anamika; Gebhart, Mathias; Fritsch, Reinhard; Sinnegger-Brauns, Martina J; Poggiani, Chiara; Hoda, Jean-Charles; Engel, Jutta; Romanin, Christoph; Striessnig, Jörg; Koschak, Alexandra

2008-07-25

Low voltage activation of Ca(V)1.3 L-type Ca(2+) channels controls excitability in sensory cells and central neurons as well as sinoatrial node pacemaking. Ca(V)1.3-mediated pacemaking determines neuronal vulnerability of dopaminergic striatal neurons affected in Parkinson disease. We have previously found that in Ca(V)1.4 L-type Ca(2+) channels, activation, voltage, and calcium-dependent inactivation are controlled by an intrinsic distal C-terminal modulator. Because alternative splicing in the Ca(V)1.3 alpha1 subunit C terminus gives rise to a long (Ca(V)1.3(42)) and a short form (Ca(V)1.3(42A)), we investigated if a C-terminal modulatory mechanism also controls Ca(V)1.3 gating. The biophysical properties of both splice variants were compared after heterologous expression together with beta3 and alpha2delta1 subunits in HEK-293 cells. Activation of calcium current through Ca(V)1.3(42A) channels was more pronounced at negative voltages, and inactivation was faster because of enhanced calcium-dependent inactivation. By investigating several Ca(V)1.3 channel truncations, we restricted the modulator activity to the last 116 amino acids of the C terminus. The resulting Ca(V)1.3(DeltaC116) channels showed gating properties similar to Ca(V)1.3(42A) that were reverted by co-expression of the corresponding C-terminal peptide C(116). Fluorescence resonance energy transfer experiments confirmed an intramolecular protein interaction in the C terminus of Ca(V)1.3 channels that also modulates calmodulin binding. These experiments revealed a novel mechanism of channel modulation enabling cells to tightly control Ca(V)1.3 channel activity by alternative splicing. The absence of the C-terminal modulator in short splice forms facilitates Ca(V)1.3 channel activation at lower voltages expected to favor Ca(V)1.3 activity at threshold voltages as required for modulation of neuronal firing behavior and sinoatrial node pacemaking.

Proximal clustering between BK and CaV1.3 channels promotes functional coupling and BK channel activation at low voltage

PubMed Central

Vivas, Oscar; Moreno, Claudia M; Santana, Luis F; Hille, Bertil

2017-01-01

CaV-channel dependent activation of BK channels is critical for feedback control of both calcium influx and cell excitability. Here we addressed the functional and spatial interaction between BK and CaV1.3 channels, unique CaV1 channels that activate at low voltages. We found that when BK and CaV1.3 channels were co-expressed in the same cell, BK channels started activating near −50 mV, ~30 mV more negative than for activation of co-expressed BK and high-voltage activated CaV2.2 channels. In addition, single-molecule localization microscopy revealed striking clusters of CaV1.3 channels surrounding clusters of BK channels and forming a multi-channel complex both in a heterologous system and in rat hippocampal and sympathetic neurons. We propose that this spatial arrangement allows tight tracking between local BK channel activation and the gating of CaV1.3 channels at quite negative membrane potentials, facilitating the regulation of neuronal excitability at voltages close to the threshold to fire action potentials. DOI: http://dx.doi.org/10.7554/eLife.28029.001 PMID:28665272

Aero-Optical Investigation of a Pod Directed Energy System

DTIC Science & Technology

2010-02-28

mounted in an enclosure and is now being used to record unsteady wavefront data. 31 Reference [1] Gordeyev , S., and Jumper , E.J., “Aero... Jumper , E. J., “Forcing of a Two-Dimensional, Weakly-Compressible Subsonic Free Shear Layer,” AIAA 2006-0561, Jan., 2006. [3] Gordeyev , S., Hayden, T...and Jumper , E., “Aero-Optical and Flow Measurements Over a Flat-Windowed Turret,” AIAA Journal, Vol. 45, No. 2, 2007, pp.347-357. [4] Gordeyev , S

78 FR 22168 - Airworthiness Directives; International Aero Engines AG Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-15

... Airworthiness Directives; International Aero Engines AG Turbofan Engines AGENCY: Federal Aviation Administration... International Aero Engines AG (IAE), V2525-D5 and V2528-D5 turbofan engines, with a certain No. 4 bearing... turbofan engines, serial numbers V20001 through V20285, with No. 4 bearing internal scavenge tube, part...

Down-regulation of T-type Cav3.2 channels by hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1): Evidence of a signaling complex

PubMed Central

Fan, Jing; Gandini, Maria A.; Zhang, Fang-Xiong; Chen, Lina; Souza, Ivana A.; Zamponi, Gerald W.

2017-01-01

ABSTRACT Formation of complexes between ion channels is important for signal processing in the brain. Here we investigate the biochemical and biophysical interactions between HCN1 channels and Cav3.2 T-type channels. We found that HCN1 co-immunoprecipitated with Cav3.2 from lysates of either mouse brain or tsA-201 cells, with the HCN1 N-terminus associating with the Cav3.2 N-terminus. Cav3.2 channel activity appeared to be functionally regulated by HCN1. The expression of HCN1 induced a decrease in Cav3.2 Ba2+ influx (IBa2+) along with altered channel kinetics and a depolarizing shift in activation gating. However, a reciprocal regulation of HCN1 by Cav3.2 was not observed. This study highlights a regulatory role of HCN1 on Cav3.2 voltage-dependent properties, which are expected to affect physiologic functions such as synaptic transmission and cellular excitability. PMID:28467171

Transcription factor Sp1 regulates T-type Ca(2+) channel CaV 3.1 gene expression.

PubMed

González-Ramírez, Ricardo; Martínez-Hernández, Elizabeth; Sandoval, Alejandro; Felix, Ricardo

2014-05-01

Voltage-gated T-type Ca(2+) (CaV 3) channels mediate a number of physiological events in developing and mature cells, and are implicated in neurological and cardiovascular diseases. In mammals, there are three distinct T-channel genes (CACNA1G, CACNA1H, and CACNA1I) encoding proteins (CaV 3.1-CaV 3.3) that differ in their localization as well as in molecular, biophysical, and pharmacological properties. The CACNA1G is a large gene that contains 38 exons and is localized in chromosome 17q22. Only basic characteristics of the CACNA1G gene promoter region have been investigated classifying it as a TATA-less sequence containing several potential transcription factor-binding motifs. Here, we cloned and characterized a proximal promoter region and initiated the analysis of transcription factors that control CaV 3.1 channel expression using the murine Cacna1g gene as a model. We isolated a ∼1.5 kb 5'-upstream region of Cacna1g and verified its transcriptional activity in the mouse neuroblastoma N1E-115 cell line. In silico analysis revealed that this region possesses a TATA-less minimal promoter that includes two potential transcription start sites and four binding sites for the transcription factor Sp1. The ability of one of these sites to interact with the transcription factor was confirmed by electrophoretic mobility shift assays. Consistent with this, Sp1 over-expression enhanced promoter activity while siRNA-mediated Sp1 silencing significantly decreased the level of CaV 3.1 protein and reduced the amplitude of whole-cell T-type Ca(2+) currents expressed in the N1E-115 cells. These results provide new insights into the molecular mechanisms that control CaV 3.1 channel expression. © 2013 Wiley Periodicals, Inc.

Tissue-selective restriction of RNA editing of CaV1.3 by splicing factor SRSF9.

PubMed

Huang, Hua; Kapeli, Katannya; Jin, Wenhao; Wong, Yuk Peng; Arumugam, Thiruma Valavan; Koh, Joanne Huifen; Srimasorn, Sumitra; Mallilankaraman, Karthik; Chua, John Jia En; Yeo, Gene W; Soong, Tuck Wah

2018-05-04

Adenosine DeAminases acting on RNA (ADAR) catalyzes adenosine-to-inosine (A-to-I) conversion within RNA duplex structures. While A-to-I editing is often dynamically regulated in a spatial-temporal manner, the mechanisms underlying its tissue-selective restriction remain elusive. We have previously reported that transcripts of voltage-gated calcium channel CaV1.3 are subject to brain-selective A-to-I RNA editing by ADAR2. Here, we show that editing of CaV1.3 mRNA is dependent on a 40 bp RNA duplex formed between exon 41 and an evolutionarily conserved editing site complementary sequence (ECS) located within the preceding intron. Heterologous expression of a mouse minigene that contained the ECS, intermediate intronic sequence and exon 41 with ADAR2 yielded robust editing. Interestingly, editing of CaV1.3 was potently inhibited by serine/arginine-rich splicing factor 9 (SRSF9). Mechanistically, the inhibitory effect of SRSF9 required direct RNA interaction. Selective down-regulation of SRSF9 in neurons provides a basis for the neuron-specific editing of CaV1.3 transcripts.

76 FR 27872 - Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Model P-180 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-13

... Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Model P- 180 Airplanes AGENCY: Federal Aviation.... This emergency AD was sent previously to all known U.S. owners and operators of PIAGGIO AERO INDUSTRIES... loss of control of the aeroplane. Since these AD actions were taken, Piaggio Aero Industries, the type...

Ser1928 phosphorylation by PKA stimulates the L-type Ca2+ channel CaV1.2 and vasoconstriction during acute hyperglycemia and diabetes

PubMed Central

Nystoriak, Matthew A.; Nieves-Cintrón, Madeline; Patriarchi, Tommaso; Buonarati, Olivia R.; Prada, Maria Paz; Morotti, Stefano; Grandi, Eleonora; Fernandes, Julia Dos Santos; Forbush, Katherine; Hofmann, Franz; Sasse, Kent C.; Scott, John D.; Ward, Sean M.; Hell, Johannes W.; Navedo, Manuel F.

2017-01-01

Hypercontractility of arterial myocytes and enhanced vascular tone during diabetes are, in part, attributed to the effects of increased glucose (hyperglycemia) on L-type CaV1.2 channels. In murine arterial myocytes, kinase-dependent mechanisms mediate the increase in CaV1.2 activity in response to increased extracellular glucose. We identified a subpopulation of the CaV1.2 channel pore-forming subunit (α1C) within nanometer proximity of protein kinase A (PKA) at the sarcolemma of murine and human arterial myocytes. This arrangement depended upon scaffolding of PKA by an A-kinase anchoring protein 150 (AKAP150) in mice. Glucose-mediated increases in CaV1.2 channel activity were associated with PKA activity, leading to α1C phosphorylation at Ser1928. Compared to arteries from low-fat diet (LFD)–fed mice and nondiabetic patients, arteries from high-fat diet (HFD)–fed mice and from diabetic patients had increased Ser1928 phosphorylation and CaV1.2 activity. Arterial myocytes and arteries from mice lacking AKAP150 or expressing mutant AKAP150 unable to bind PKA did not exhibit increased Ser1928 phosphorylation and CaV1.2 current density in response to increased glucose or to HFD. Consistent with a functional role for Ser1928 phosphorylation, arterial myocytes and arteries from knockin mice expressing a CaV1.2 with Ser1928 mutated to alanine (S1928A) lacked glucose-mediated increases in CaV1.2 activity and vasoconstriction. Furthermore, the HFD-induced increases in CaV1.2 current density and myogenic tone were prevented in S1928A knockin mice. These findings reveal an essential role for α1C phosphorylation at Ser1928 in stimulating CaV1.2 channel activity and vasoconstriction by AKAP-targeted PKA upon exposure to increased glucose and in diabetes. PMID:28119464

78 FR 69600 - Airworthiness Directives; Piaggio Aero Industries S.p.A Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-20

... p.m., Monday through Friday, except Federal holidays. For service information identified in this.... To address this potential unsafe condition, Piaggio Aero Industries (PAI) issued Service [[Page 69601... Service Information Piaggio Aero Industries S.p.A. has issued Mandatory Service Bulletin No.: 80-0381, Rev...

Ascent Heating Thermal Analysis on the Spacecraft Adaptor (SA) Fairings and the Interface with the Crew Launch Vehicle (CLV)

NASA Technical Reports Server (NTRS)

Wang, Xiao-Yen; Yuko, James; Motil, Brian

2009-01-01

When the crew exploration vehicle (CEV) is launched, the spacecraft adaptor (SA) fairings that cover the CEV service module (SM) are exposed to aero heating. Thermal analysis is performed to compute the fairing temperatures and to investigate whether the temperatures are within the material limits for nominal ascent aero heating case. Heating rates from Thermal Environment (TE) 3 aero heating analysis computed by engineers at Marshall Space Flight Center (MSFC) are used in the thermal analysis. Both MSC Patran 2007r1b/Pthermal and C&R Thermal Desktop 5.1/Sinda models are built to validate each other. The numerical results are also compared with those reported by Lockheed Martin (LM) and show a reasonably good agreement.

Divergent biophysical properties, gating mechanisms, and possible functions of the two skeletal muscle Ca(V)1.1 calcium channel splice variants.

PubMed

Tuluc, Petronel; Flucher, Bernhard E

2011-12-01

Voltage-gated calcium channels are multi-subunit protein complexes that specifically allow calcium ions to enter the cell in response to membrane depolarization. But, for many years it seemed that the skeletal muscle calcium channel Ca(V)1.1 is the exception. The classical splice variant Ca(V)1.1a activates slowly, has a very small current amplitude and poor voltage sensitivity. In fact adult muscle fibers work perfectly well even in the absence of calcium influx. Recently a new splice variant of the skeletal muscle calcium channel Ca(V)1.1e has been characterized. The lack of the 19 amino acid exon 29 in this splice variant results in a rapidly activating calcium channel with high current amplitude and good voltage sensitivity. Ca(V)1.1e is the dominant channel in embryonic muscle, where the expression of this high calcium-conducting Ca(V)1.1 isoform readily explains developmental processes depending on L-type calcium currents. Moreover, the availability of these two structurally similar but functionally distinct channel variants facilitates the analysis of the molecular mechanisms underlying the unique current properties of the classical Ca(V)1.1a channel.

Reduction of Cav1.3 channels in dorsal hippocampus impairs the development of dentate gyrus newborn neurons and hippocampal-dependent memory tasks

PubMed Central

Kim, Su-Hyun; Park, Ye-Ryoung; Lee, Boyoung; Choi, Byungil; Kim, Hyun

2017-01-01

Cav1.3 has been suggested to mediate hippocampal neurogenesis of adult mice and contribute to hippocampal-dependent learning and memory processes. However, the mechanism of Cav1.3 contribution in these processes is unclear. Here, roles of Cav1.3 of mouse dorsal hippocampus during newborn cell development were examined. We find that knock-out (KO) of Cav1.3 resulted in the reduction of survival of newborn neurons at 28 days old after mitosis. The retroviral eGFP expression showed that both dendritic complexity and the number and length of mossy fiber bouton (MFB) filopodia of newborn neurons at ≥ 14 days old were significantly reduced in KO mice. Both contextual fear conditioning (CFC) and object-location recognition tasks were impaired in recent (1 day) memory test while passive avoidance task was impaired only in remote (≥ 20 days) memory in KO mice. Results using adeno-associated virus (AAV)-mediated Cav1.3 knock-down (KD) or retrovirus-mediated KD in dorsal hippocampal DG area showed that the recent memory of CFC was impaired in both KD mice but the remote memory was impaired only in AAV KD mice, suggesting that Cav1.3 of mature neurons play important roles in both recent and remote CFC memory while Cav1.3 in newborn neurons is selectively involved in the recent CFC memory process. Meanwhile, AAV KD of Cav1.3 in ventral hippocampal area has no effect on the recent CFC memory. In conclusion, the results suggest that Cav1.3 in newborn neurons of dorsal hippocampus is involved in the survival of newborn neurons while mediating developments of dendritic and axonal processes of newborn cells and plays a role in the memory process differentially depending on the stage of maturation and the type of learning task. PMID:28715454

Reduction of Cav1.3 channels in dorsal hippocampus impairs the development of dentate gyrus newborn neurons and hippocampal-dependent memory tasks.

PubMed

Kim, Su-Hyun; Park, Ye-Ryoung; Lee, Boyoung; Choi, Byungil; Kim, Hyun; Kim, Chong-Hyun

2017-01-01

Cav1.3 has been suggested to mediate hippocampal neurogenesis of adult mice and contribute to hippocampal-dependent learning and memory processes. However, the mechanism of Cav1.3 contribution in these processes is unclear. Here, roles of Cav1.3 of mouse dorsal hippocampus during newborn cell development were examined. We find that knock-out (KO) of Cav1.3 resulted in the reduction of survival of newborn neurons at 28 days old after mitosis. The retroviral eGFP expression showed that both dendritic complexity and the number and length of mossy fiber bouton (MFB) filopodia of newborn neurons at ≥ 14 days old were significantly reduced in KO mice. Both contextual fear conditioning (CFC) and object-location recognition tasks were impaired in recent (1 day) memory test while passive avoidance task was impaired only in remote (≥ 20 days) memory in KO mice. Results using adeno-associated virus (AAV)-mediated Cav1.3 knock-down (KD) or retrovirus-mediated KD in dorsal hippocampal DG area showed that the recent memory of CFC was impaired in both KD mice but the remote memory was impaired only in AAV KD mice, suggesting that Cav1.3 of mature neurons play important roles in both recent and remote CFC memory while Cav1.3 in newborn neurons is selectively involved in the recent CFC memory process. Meanwhile, AAV KD of Cav1.3 in ventral hippocampal area has no effect on the recent CFC memory. In conclusion, the results suggest that Cav1.3 in newborn neurons of dorsal hippocampus is involved in the survival of newborn neurons while mediating developments of dendritic and axonal processes of newborn cells and plays a role in the memory process differentially depending on the stage of maturation and the type of learning task.

Identified state-space prediction model for aero-optical wavefronts

NASA Astrophysics Data System (ADS)

Faghihi, Azin; Tesch, Jonathan; Gibson, Steve

2013-07-01

A state-space disturbance model and associated prediction filter for aero-optical wavefronts are described. The model is computed by system identification from a sequence of wavefronts measured in an airborne laboratory. Estimates of the statistics and flow velocity of the wavefront data are shown and can be computed from the matrices in the state-space model without returning to the original data. Numerical results compare velocity values and power spectra computed from the identified state-space model with those computed from the aero-optical data.

Review: Cav2.3 R-type Voltage-Gated Ca2+ Channels - Functional Implications in Convulsive and Non-convulsive Seizure Activity

PubMed Central

Wormuth, Carola; Lundt, Andreas; Henseler, Christina; Müller, Ralf; Broich, Karl; Papazoglou, Anna; Weiergräber, Marco

2016-01-01

Background: Researchers have gained substantial insight into mechanisms of synaptic transmission, hyperexcitability, excitotoxicity and neurodegeneration within the last decades. Voltage-gated Ca2+ channels are of central relevance in these processes. In particular, they are key elements in the etiopathogenesis of numerous seizure types and epilepsies. Earlier studies predominantly targeted on Cav2.1 P/Q-type and Cav3.2 T-type Ca2+ channels relevant for absence epileptogenesis. Recent findings bring other channels entities more into focus such as the Cav2.3 R-type Ca2+ channel which exhibits an intriguing role in ictogenesis and seizure propagation. Cav2.3 R-type voltage gated Ca2+ channels (VGCC) emerged to be important factors in the pathogenesis of absence epilepsy, human juvenile myoclonic epilepsy (JME), and cellular epileptiform activity, e.g. in CA1 neurons. They also serve as potential target for various antiepileptic drugs, such as lamotrigine and topiramate. Objective: This review provides a summary of structure, function and pharmacology of VGCCs and their fundamental role in cellular Ca2+ homeostasis. We elaborate the unique modulatory properties of Cav2.3 R-type Ca2+ channels and point to recent findings in the proictogenic and proneuroapoptotic role of Cav2.3 R-type VGCCs in generalized convulsive tonic–clonic and complex-partial hippocampal seizures and its role in non-convulsive absence like seizure activity. Conclusion: Development of novel Cav2.3 specific modulators can be effective in the pharmacological treatment of epilepsies and other neurological disorders. PMID:27843503

Up-regulation of Cav3.1 expression in SH-SY5Y cells induced by lidocaine hydrochloride.

PubMed

Gong, Qin; Wen, Xianjie; Li, Heng; He, Jian; Wang, Yunhua; Wu, Huiping; Wang, Hanbing; Wang, Xiaoping

2018-01-12

Neurotoxicity induced by the local anaesthetics has aroused concern. A previous study has shown that an overload of intracellular calcium was involved in the neurotoxic effect. Cav3.1 is one of the low-voltage-activated (LVA) calcium channels which play a key point to regulate the intracellular calcium ion level. This study aimed to investigate the changes of the Cav3.1 expression in the SH-SY5Y cells treated with lidocaine hydrochloride. The SH-SY5Y cells were treated with different concentrations of lidocaine hydrochloride(1 mM, 5 mM and 10 mM, namely L1 group, L5 group and L10 group) and different exposure times (1 h,12 h and 24 h), respectively. Cell viability, Cav3.1 protein and mRNA expression were detected. The results showed that cell viability decreased and Cav3.1 mRNA and protein expression increased with the concentration (from 1 mM to 10 mM) of the lidocaine hydrochloride and exposure time (from 1 h to 24 h) to the SH-SY5Y cell line increased. Those data showed that lidocaine hydrochloride induced SH-SY5Y cell toxicity and up-regulated Cav3.1mRNA and protein expression.

Results of the AEROS satellite program: Summary

NASA Technical Reports Server (NTRS)

Lammerzahl, P.; Rawer, K.; Roemer, N.

1980-01-01

Published literature reporting aeronomic data collected on two AEROS missions is summarized. The extreme ultraviolet solar radiation and other significant parameters of the thermosphere/ionosphere were investigated. Kinetic pressure, the quantity of atomic nitrogen, and partial densities of helium, oxygen, nitrogen, argon, and atomic nitrogen were determined. The thermal electron population, superthermal energy distribution, plasma density, ion temperature, and composition according to ion types were measured. The chief energy supply in the thermosphere was calculated. Aeronomic calculations showing that variations in the parameters of the ionosphere cannot be correlated with fluctuations of extreme ultraviolet solar radiation were performed. The AEROS data were compared with data from S3-1, ISIS, and AE-C satellites. Models of the thermosphere and ionosphere were developed.

Current Challenges for HTCMC Aero-Propulsion Components

NASA Technical Reports Server (NTRS)

DiCarlo, James A.; Bansal, Narottam P.

2007-01-01

In comparison to the best metallic materials, HTCMC aero-propulsion engine components offer the opportunity of reduced weight and higher temperature operation, with corresponding improvements in engine cooling requirements, emissions, thrust, and specific fuel consumption. Although much progress has been made in the development of advanced HTCMC constituent materials and processes, major challenges still remain for their implementation into these components. The objectives of this presentation are to briefly review (1) potential HTCMC aero-propulsion components and their generic material performance requirements, (2) recent progress at NASA and elsewhere concerning advanced constituents and processes for meeting these requirements, (3) key HTCMC component implementation challenges that are currently being encountered, and (4) on-going activities within the new NASA Fundamental Aeronautics Program that are addressing these challenges.

78 FR 49662 - Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-15

... Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Airplanes AGENCY: Federal Aviation Administration (FAA... airworthiness directive (AD) for PIAGGIO AERO INDUSTRIES S.p.A. Model P-180 airplanes. The rescinded AD resulted... to develop on affected type design airplanes. DATES: This AD is effective September 19, 2013...

76 FR 54403 - Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Model PIAGGIO P-180 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-01

... Federal holidays. For service information identified in this proposed AD, contact Piaggio Aero Industries... Service Information Piaggio Aero Industries S.p.A. has issued Mandatory Service Bulletin No. 80-0304... Accomplishment Instructions of Piaggio Aero Industries S.p.A. Mandatory Service Bulletin No. 80-0304, dated July...

DEMONSTRATION BULLETIN: CAV-OX ULTRAVIOLET OXIDATION PROCESS MAGNUM WATER TECHNOLOGY

EPA Science Inventory

The CAV-OX® technology (see Fig- ure 1) destroys organic contaminants, including chlorinated hy- drocarbons, in water. The process uses hydrogen peroxide, hy- drodynamic cavitation, and ultraviolet (UV) radiation to photolyze and oxidize organic compounds present in water at ...

76 FR 77369 - Airworthiness Directives; Piaggio Aero Industries S.p.A. Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-13

... installed on the door handle for proper tightness and correct as necessary after applying a thread locker... thread locker following Part D of the Accomplishment Instructions in Piaggio Aero Industries S.p.A... necessary after applying a thread locker following Part D of the Accomplishment Instructions in Piaggio Aero...

78 FR 32363 - Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-30

... Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Airplanes AGENCY: Federal Aviation Administration (FAA... propose to rescind an airworthiness directive (AD) for PIAGGIO AERO INDUSTRIES S.p.A. Model P-180... or is not likely to develop on affected type design airplanes, and therefore the AD should be...

NK receptors, Substance P, Ano1 expression and ultrastructural features of the muscle coat in Cav-1(-/-) mouse ileum.

PubMed

Cipriani, G; Serboiu, Crenguta S; Gherghiceanu, Mihaela; Faussone-Pellegrini, Maria Simonetta; Vannucchi, Maria Giuliana

2011-11-01

Caveolin (Cav)-1 is an integral membrane protein of caveolae playing a crucial role in various signal transduction pathways. Caveolae represent the sites for calcium entry and storage especially in smooth muscle cells (SMC) and interstitial cells of Cajal (ICC). Cav-1(-/-) mice lack caveolae and show abnormalities in pacing and contractile activity of the small intestine. Presently, we investigated, by transmission electron microscopy (TEM) and immunohistochemistry, whether the absence of Cav-1 in Cav-1(-/-) mouse small intestine affects ICC, SMC and neuronal morphology, the expression of NK1 and NK2 receptors, and of Ano1 (also called Dog1 or TMEM16A), an essential molecule for slow wave activity in gastrointestinal muscles. ICC were also labelled with c-Kit and tachykinergic neurons with Substance P (SP). In Cav-1(-/-) mice: (i) ICC were Ano1-negative but maintained c-Kit expression, (ii) NK1 and NK2 receptor immunoreactivity was more intense and, in the SMC, mainly intracytoplasmatic, (iii) SP-immunoreactivity was significantly reduced. Under TEM: (i) ICC, SMC and telocytes lacked typical caveolae but had few and large flask-shaped vesicles we called large-sized caveolae; (ii) SMC and ICC contained an extraordinary high number of mitochondria, (iii) neurons were unchanged. To maintain intestinal motility, loss of caveolae and reduced calcium availability in Cav-1-knockout mice seem to be balanced by a highly increased number of mitochondria in ICC and SMC. Loss of Ano-1 expression, decrease of SP content and consequently overexpression of NK receptors suggest that all these molecules are Cav-1-associated proteins. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Fault Diagnosis of Demountable Disk-Drum Aero-Engine Rotor Using Customized Multiwavelet Method.

PubMed

Chen, Jinglong; Wang, Yu; He, Zhengjia; Wang, Xiaodong

2015-10-23

The demountable disk-drum aero-engine rotor is an important piece of equipment that greatly impacts the safe operation of aircraft. However, assembly looseness or crack fault has led to several unscheduled breakdowns and serious accidents. Thus, condition monitoring and fault diagnosis technique are required for identifying abnormal conditions. Customized ensemble multiwavelet method for aero-engine rotor condition identification, using measured vibration data, is developed in this paper. First, customized multiwavelet basis function with strong adaptivity is constructed via symmetric multiwavelet lifting scheme. Then vibration signal is processed by customized ensemble multiwavelet transform. Next, normalized information entropy of multiwavelet decomposition coefficients is computed to directly reflect and evaluate the condition. The proposed approach is first applied to fault detection of an experimental aero-engine rotor. Finally, the proposed approach is used in an engineering application, where it successfully identified the crack fault of a demountable disk-drum aero-engine rotor. The results show that the proposed method possesses excellent performance in fault detection of aero-engine rotor. Moreover, the robustness of the multiwavelet method against noise is also tested and verified by simulation and field experiments.

Fault Diagnosis of Demountable Disk-Drum Aero-Engine Rotor Using Customized Multiwavelet Method

PubMed Central

Chen, Jinglong; Wang, Yu; He, Zhengjia; Wang, Xiaodong

2015-01-01

The demountable disk-drum aero-engine rotor is an important piece of equipment that greatly impacts the safe operation of aircraft. However, assembly looseness or crack fault has led to several unscheduled breakdowns and serious accidents. Thus, condition monitoring and fault diagnosis technique are required for identifying abnormal conditions. Customized ensemble multiwavelet method for aero-engine rotor condition identification, using measured vibration data, is developed in this paper. First, customized multiwavelet basis function with strong adaptivity is constructed via symmetric multiwavelet lifting scheme. Then vibration signal is processed by customized ensemble multiwavelet transform. Next, normalized information entropy of multiwavelet decomposition coefficients is computed to directly reflect and evaluate the condition. The proposed approach is first applied to fault detection of an experimental aero-engine rotor. Finally, the proposed approach is used in an engineering application, where it successfully identified the crack fault of a demountable disk-drum aero-engine rotor. The results show that the proposed method possesses excellent performance in fault detection of aero-engine rotor. Moreover, the robustness of the multiwavelet method against noise is also tested and verified by simulation and field experiments. PMID:26512668

Mosaic synaptopathy and functional defects in Cav1.4 heterozygous mice and human carriers of CSNB2

PubMed Central

Michalakis, Stylianos; Shaltiel, Lior; Sothilingam, Vithiyanjali; Koch, Susanne; Schludi, Verena; Krause, Stefanie; Zeitz, Christina; Audo, Isabelle; Lancelot, Marie-Elise; Hamel, Christian; Meunier, Isabelle; Preising, Markus N.; Friedburg, Christoph; Lorenz, Birgit; Zabouri, Nawal; Haverkamp, Silke; Garrido, Marina Garcia; Tanimoto, Naoyuki; Seeliger, Mathias W.; Biel, Martin; Wahl-Schott, Christian A.

2014-01-01

Mutations in CACNA1F encoding the α1-subunit of the retinal Cav1.4 L-type calcium channel have been linked to Cav1.4 channelopathies including incomplete congenital stationary night blindness type 2A (CSNB2), Åland Island eye disease (AIED) and cone-rod dystrophy type 3 (CORDX3). Since CACNA1F is located on the X chromosome, Cav1.4 channelopathies are typically affecting male patients via X-chromosomal recessive inheritance. Occasionally, clinical symptoms have been observed in female carriers, too. It is currently unknown how these mutations lead to symptoms in carriers and how the retinal network in these females is affected. To investigate these clinically important issues, we compared retinal phenotypes in Cav1.4-deficient and Cav1.4 heterozygous mice and in human female carrier patients. Heterozygous Cacna1f carrier mice have a retinal mosaic consistent with differential X-chromosomal inactivation, characterized by adjacent vertical columns of affected and non-affected wild-type-like retinal network. Vertical columns in heterozygous mice are well comparable to either the wild-type retinal network of normal mice or to the retina of homozygous mice. Affected retinal columns display pronounced rod and cone photoreceptor synaptopathy and cone degeneration. These changes lead to vastly impaired vision-guided navigation under dark and normal light conditions and reduced retinal electroretinography (ERG) responses in Cacna1f carrier mice. Similar abnormal ERG responses were found in five human CACNA1F carriers, four of which had novel mutations. In conclusion, our data on Cav1.4 deficient mice and human female carriers of mutations in CACNA1F are consistent with a phenotype of mosaic CSNB2. PMID:24163243

77 FR 67764 - Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-14

... Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Airplanes AGENCY: Federal Aviation Administration (FAA... directive (AD) for certain Piaggio Aero Industries S.p.A. Model P-180 airplanes. That AD currently requires...., Washington, DC 20590, between 9 a.m. and 5 p.m., Monday through Friday, except Federal holidays. For service...

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2012-09-17

... identified in this AD, contact Piaggio Aero Industries S.p.A--Airworthiness Office, Via Luigi Cibrario, 4..., contact Piaggio Aero Industries S.p.A-- Airworthiness Office, Via Luigi Cibrario, 4-16154 Genova-Italy... #0; #0;Rules and Regulations #0; Federal Register #0; #0; #0;This section of the FEDERAL REGISTER...

78 FR 69597 - Airworthiness Directives; Piaggio Aero Industries S.p.A Airplanes

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2013-11-20

... Industries S.p.A Airplanes AGENCY: Federal Aviation Administration (FAA), Department of Transportation (DOT... (AD) for Piaggio Aero Industries S.p.A Model P-180 airplanes that would supersede an existing AD. This... proposed AD, contact Piaggio Aero Industries S.p.A-Airworthiness Office, Via Luigi Cibrario, 4-16154 Genova...

Application of Multihop Relay for Performance Enhancement of AeroMACS Networks

NASA Technical Reports Server (NTRS)

Kamali, Behnam; Wilson, Jeffrey D.; Kerczewski, Robert J.

2012-01-01

A new transmission technology, based on IEEE 802.16-2009 (WiMAX), is currently being developed for airport surface communications. A C-band spectrum allocation at 5091-5150 MHz has been created by ITU to carry this application. The proposed technology, known as AeroMACS, will be used to support fixed and mobile ground to ground applications and services. This article proposes and demonstrates that IEEE 802.16j-amendment-based WiMAX is most feasible for AeroMACS applications. This amendment introduces multihop relay as an optional deployment that may be used to provide additional coverage and/or enhance the capacity of the network. Particular airport surface radio coverage situations for which IEEE 802.16-2009-WiMAX provides resolutions that are inefficient, costly, or excessively power consuming are discussed. In all these cases, it is argued that 16j technology offers a much better alternative. A major concern about deployment of AeroMACS is interference to co-allocated applications such as the Mobile Satellite Service (MSS) feeder link. Our initial simulation results suggest that no additional interference to MSS feeder link is caused by deployment of IEEE 802.16j-based AeroMACS.

Application of Multihop Relay for Performance Enhancement of AeroMACS Networks

NASA Technical Reports Server (NTRS)

Kamali, Behnam; Wilson, Jeffrey D.; Kerczewski, Robert J.

2012-01-01

A new transmission technology, based on IEEE 802.16-2009 (WiMAX), is currently being developed for airport surface communications. A C-band spectrum allocation at 5091 to 5150 MHz has been created by International Telecommunications Union (ITU) to carry this application. The proposed technology, known as AeroMACS, will be used to support fixed and mobile ground to ground applications and services. This article proposes and demonstrates that IEEE 802.16j-amendment-based WiMAX is most feasible for AeroMACS applications. This amendment introduces multihop relay as an optional deployment that may be used to provide additional coverage and/or enhance the capacity of the network. Particular airport surface radio coverage situations for which IEEE 802.16-2009-WiMAX provides resolutions that are inefficient, costly, or excessively power consuming are discussed. In all these cases, it is argued that 16j technology offers a much better alternative. A major concern about deployment of AeroMACS is interference to co-allocated applications such as the Mobile Satellite Service (MSS) feeder link. Our initial simulation results suggest that no additional interference to MSS feeder link is caused by deployment of IEEE 802.16j-based AeroMACS.

Aero-Thermal Calibration of the NASA Glenn Icing Research Tunnel (2012 Test)

NASA Technical Reports Server (NTRS)

Pastor-Barsi, Christine M.; Arrington, E. Allen; VanZante, Judith Foss

2012-01-01

A major modification of the refrigeration plant and heat exchanger at the NASA Glenn Icing Research Tunnel (IRT) occurred in autumn of 2011. It is standard practice at NASA Glenn to perform a full aero-thermal calibration of the test section of a wind tunnel facility upon completion of major modifications. This paper will discuss the tools and techniques used to complete an aero-thermal calibration of the IRT and the results that were acquired. The goal of this test entry was to complete a flow quality survey and aero-thermal calibration measurements in the test section of the IRT. Test hardware that was used includes the 2D Resistive Temperature Detector (RTD) array, 9-ft pressure survey rake, hot wire survey rake, and the quick check survey rake. This test hardware provides a map of the velocity, Mach number, total and static pressure, total temperature, flow angle and turbulence intensity. The data acquired were then reduced to examine pressure, temperature, velocity, flow angle, and turbulence intensity. Reduced data has been evaluated to assess how the facility meets flow quality goals. No icing conditions were tested as part of the aero-thermal calibration. However, the effects of the spray bar air injections on the flow quality and aero-thermal calibration measurements were examined as part of this calibration.

Improvement of the AeroClipper system for cyclones monitoring

NASA Astrophysics Data System (ADS)

Vargas, André; Philippe, Duvel Jean

2016-07-01

The AeroClipper developed by the French space agency (Centre National d'Études Spatiales, CNES) is a quasi-lagrangian device drifting with surface wind at about 20-30m above the ocean surface. It is a new and original device for real-time and continuous observation of air-sea surface parameters in open ocean remote regions. This device enables the sampling of the variability of surface parameters in particular under convective systems toward which it is attracted. The AeroClipper is therefore an ideal instrument to monitor Tropical Cyclones (TCs) in which they are likely to converge and provide original observations to evaluate and improve our current understanding and diagnostics of TCs as well as their representation in numerical models. In 2008, the AeroClipper demonstrates its capability to be captured by an Ocean Indian cyclone, as two models have converged, without damages, in the eye of Dora cyclone during the 2008 VASCO campaign. This paper will present the improvements of this balloon system for the international project 'the Year of Maritime Continent'.

77 FR 35888 - Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-15

...., Washington, DC 20590, between 9 a.m. and 5 p.m., Monday through Friday, except Federal holidays. For service.... Relevant Service Information PIAGGIO AERO INDUSTRIES S.p.A. has issued Service Bulletin No. 80- 0318, dated... Instructions of Piaggio Aero Industries S.p.A. Mandatory Service Bulletin No. 80-0318, revision 2, dated March...

76 FR 60396 - Airworthiness Directives; Piaggio Aero Industries S.p.A. Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-29

...., Washington, DC 20590, between 9 a.m. and 5 p.m., Monday through Friday, except Federal holidays. For service... on other P.180 aeroplanes, and Piaggio Aero Industries (PAI) had issued Service Bulletin (SB) No. 80... information by examining the MCAI in the AD docket. Relevant Service Information Piaggio Aero Industries S.p.A...

Atmospheric Turbulence Modeling for Aero Vehicles: Fractional Order Fits

NASA Technical Reports Server (NTRS)

Kopasakis, George

2015-01-01

Atmospheric turbulence models are necessary for the design of both inlet/engine and flight controls, as well as for studying coupling between the propulsion and the vehicle structural dynamics for supersonic vehicles. Models based on the Kolmogorov spectrum have been previously utilized to model atmospheric turbulence. In this paper, a more accurate model is developed in its representative fractional order form, typical of atmospheric disturbances. This is accomplished by first scaling the Kolmogorov spectral to convert them into finite energy von Karman forms and then by deriving an explicit fractional circuit-filter type analog for this model. This circuit model is utilized to develop a generalized formulation in frequency domain to approximate the fractional order with the products of first order transfer functions, which enables accurate time domain simulations. The objective of this work is as follows. Given the parameters describing the conditions of atmospheric disturbances, and utilizing the derived formulations, directly compute the transfer function poles and zeros describing these disturbances for acoustic velocity, temperature, pressure, and density. Time domain simulations of representative atmospheric turbulence can then be developed by utilizing these computed transfer functions together with the disturbance frequencies of interest.

Atmospheric Turbulence Modeling for Aero Vehicles: Fractional Order Fits

NASA Technical Reports Server (NTRS)

Kopasakis, George

2010-01-01

Atmospheric turbulence models are necessary for the design of both inlet/engine and flight controls, as well as for studying coupling between the propulsion and the vehicle structural dynamics for supersonic vehicles. Models based on the Kolmogorov spectrum have been previously utilized to model atmospheric turbulence. In this paper, a more accurate model is developed in its representative fractional order form, typical of atmospheric disturbances. This is accomplished by first scaling the Kolmogorov spectral to convert them into finite energy von Karman forms and then by deriving an explicit fractional circuit-filter type analog for this model. This circuit model is utilized to develop a generalized formulation in frequency domain to approximate the fractional order with the products of first order transfer functions, which enables accurate time domain simulations. The objective of this work is as follows. Given the parameters describing the conditions of atmospheric disturbances, and utilizing the derived formulations, directly compute the transfer function poles and zeros describing these disturbances for acoustic velocity, temperature, pressure, and density. Time domain simulations of representative atmospheric turbulence can then be developed by utilizing these computed transfer functions together with the disturbance frequencies of interest.

Aerodynamic characteristics of generalized bent biconic bodies for aero-assisted, orbital-transfer vehicles

NASA Technical Reports Server (NTRS)

Davies, C. B.; Park, C.

1983-01-01

A method was developed to generate the surface coordinates of body shapes suitable for aeroassisted, orbital-transfer vehicles (AOTVs) by extending bent biconic geometries. Lift, drag, and longitudinal moments were calculated for the bodies using Newtonian flow theory. These techniques were applied to symmetric and asymmetric aerobraking vehicles, and to an aeromaneuvering vehicle with high L/D. Results for aerobraking applications indicate that a 70 deg, fore half cone angle with a spherically blunted nose, rounded edges, and a slight asymmetry would be appropriate. Moreover, results show that an aeromaneuvering vehicle with L/D 2.0, and with sufficient stability, is feasible.

Prognostic relevance of the expressions of CAV1 and TES genes on 7q31 in melanoma.

PubMed

Vizkeleti, Laura; Ecsedi, Szilvia; Rakosy, Zsuzsa; Begany, Agnes; Emri, Gabriella; Toth, Reka; Orosz, Adrienn; Szollosi, Attila Gabor; Mehes, Gabor; Adany, Roza; Balazs, Margit

2012-01-01

The 7q31 locus contains several genes affected in cancer progression. Although evidences exist regarding its impact on tumorigenesis, the role of genetic alterations and the expressions of locus-related genes are still controversial. Our study aimed to define the 7q31 copy number alterations in primary melanomas, primary-metastatic tumor pairs and cell lines. Data were correlated with clinical-pathological parameters. Genetic data show that 7q31 copy number distribution was heterogeneous in both primary and metastatic tumors. Extra copies were highly accompanied by chromosome 7 polisomy, and significantly increased in primary lesions with poor prognosis. Additionally, we determined the mRNA and protein levels of the locus-related CAV1 and TES genes. TES mRNA level was associated with metastatic location. CAV1 mRNA and protein levels were significantly higher in thicker tumors, however, lack of protein was also observed in a subpopulation of thin lesions. Expressions of CAV1 and TES were not associated with 7q31 alterations. In conclusion, 7q31 amplification can predict unfavorable outcome. Alterations of TES mRNA level may predict the location of metastasis. CAV1 possibly affect the cancer cell invasion.

NK receptors, Substance P, Ano1 expression and ultrastructural features of the muscle coat in Cav-1−/− mouse ileum

PubMed Central

Cipriani, G; Serboiu, Crenguta S; Gherghiceanu, Mihaela; Simonetta Faussone-Pellegrini, Maria; Vannucchi, Maria Giuliana

2011-01-01

Abstract Caveolin (Cav)-1 is an integral membrane protein of caveolae playing a crucial role in various signal transduction pathways. Caveolae represent the sites for calcium entry and storage especially in smooth muscle cells (SMC) and interstitial cells of Cajal (ICC). Cav-1−/− mice lack caveolae and show abnormalities in pacing and contractile activity of the small intestine. Presently, we investigated, by transmission electron microscopy (TEM) and immunohistochemistry, whether the absence of Cav-1 in Cav-1−/− mouse small intestine affects ICC, SMC and neuronal morphology, the expression of NK1 and NK2 receptors, and of Ano1 (also called Dog1 or TMEM16A), an essential molecule for slow wave activity in gastrointestinal muscles. ICC were also labelled with c-Kit and tachykinergic neurons with Substance P (SP). In Cav-1−/− mice: (i) ICC were Ano1-negative but maintained c-Kit expression, (ii) NK1 and NK2 receptor immunoreactivity was more intense and, in the SMC, mainly intracytoplasmatic, (iii) SP-immunoreactivity was significantly reduced. Under TEM: (i) ICC, SMC and telocytes lacked typical caveolae but had few and large flask-shaped vesicles we called large-sized caveolae; (ii) SMC and ICC contained an extraordinary high number of mitochondria, (iii) neurons were unchanged. To maintain intestinal motility, loss of caveolae and reduced calcium availability in Cav-1–knockout mice seem to be balanced by a highly increased number of mitochondria in ICC and SMC. Loss of Ano-1 expression, decrease of SP content and consequently overexpression of NK receptors suggest that all these molecules are Cav-1–associated proteins. PMID:21535398

The aero optics effect on near space laser communication optical system

NASA Astrophysics Data System (ADS)

Hu, Yuan; Fu, Yuegang; Jiang, Huilin

2013-08-01

With the developing of the space laser communication link, the performance index including higher transfer speed, extending transfer distance, and environmental adaptability, all ask the system accuracy and indexes improving. Special the developing near space platform, its environmental is extremes, the near space drone and other airplane flight speed is very quickly from the subsonic to supersonic. The aero optics effect caused by high speed will generate a thin turbulent air layer. It affects the performance of laser communication optical system by laser light vibration, deviation and so on, further more affects the performance of laser communication system working performance, even can't communication. Therefore, for achieving optical system indexes, we need do more research in optical system near space aero optics environmental adaptability. In this paper, near space link environmental characteristic are researched. And on the base of the aero optics theory, computer simulating method is applied to analyze the relationship among the altitude, the flight speed and the image dispersion. The result shows that, the aero optics effect cannot be ignored when the terminal is in low altitude or is moving with supersonic speed. The effect must be taken into considered from overall design. The result will provide the basis of research design.

On Proper Selection of Multihop Relays for Future Enhancement of AeroMACS Networks

NASA Technical Reports Server (NTRS)

Kamali, Behnam; Kerczewski, Robert J.; Apaza, Rafael D.

2015-01-01

As the Aeronautical Mobile Airport Communications System (AeroMACS) has evolved from a technology concept to a deployed communications network over major US airports, it is now time to contemplate whether the existing capacity of AeroMACS is sufficient to meet the demands set forth by all fixed and mobile applications over the airport surface given the AeroMACS constraints regarding bandwidth and transmit power. The underlying idea in this article is to present IEEE 802.16j-based WiMAX as a technology that can address future capacity enhancements and therefore is most feasible for AeroMACS applications. The principal argument in favor IEEE 802.16j technology is the flexible and cost effective extension of radio coverage that is afforded by relay fortified networks, with virtually no increase in the power requirements and virtually no rise in interference levels to co-allocated applications. The IEEE 802.16j-based multihop relay systems are briefly described. The focus is on key features of this technology, frame structure, and its architecture. Next, AeroMACS is described as a WiMAX-based wireless network. The two major relay modes supported by IEEE 802.16j amendment, i.e., transparent and non-transparent are described. The benefits of employing multihop relays are listed. Some key challenges related to incorporating relays into AeroMACS networks are discussed. The selection of relay type in a broadband wireless network affects a number of network parameters such as latency, signal overhead, PHY (Scalable Physical Layer) and MAC (Media Access Layer) layer protocols, consequently it can alter key network quantities of throughput and QoS (Quality of Service).

Predicting Cavitation on Marine and Hydrokinetic Turbine Blades with AeroDyn V15.04

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

Murray, Robynne

Cavitation is an important consideration in the design of marine and hydrokinetic (MHK) turbines. The National Renewable Energy Laboratory's AeroDyn performance code was originally developed for horizontal-axis wind turbines and did not have the capability to predict cavitation inception. Therefore, AeroDyn has been updated to include the ability to predict cavitation on MHK turbines based on user-specified vapor pressure and submerged depth. This report outlines a verification of the AeroDyn V15.04 performance code for MHK turbines through a comparison to publicly available performance data.

The Low-Threshold Calcium Channel Cav3.2 Mediates Burst Firing of Mature Dentate Granule Cells

PubMed Central

Dumenieu, Mael; Senkov, Oleg; Mironov, Andrey; Bourinet, Emmanuel; Kreutz, Michael R; Dityatev, Alexander; Heine, Martin; Bikbaev, Arthur

2018-01-01

Abstract Mature granule cells are poorly excitable neurons that were recently shown to fire action potentials, preferentially in bursts. It is believed that the particularly pronounced short-term facilitation of mossy fiber synapses makes granule cell bursting a very effective means of properly transferring information to CA3. However, the mechanism underlying the unique bursting behavior of mature granule cells is currently unknown. Here, we show that Cav3.2 T-type channels at the axon initial segment are responsible for burst firing of mature granule cells in rats and mice. Accordingly, Cav3.2 knockout mice fire tonic spikes and exhibit impaired bursting, synaptic plasticity and dentate-to-CA3 communication. The data show that Cav3.2 channels are strong modulators of bursting and can be considered a critical molecular switch that enables effective information transfer from mature granule cells to the CA3 pyramids. PMID:29790938

β-Subunits Promote the Expression of CaV2.2 Channels by Reducing Their Proteasomal Degradation*

PubMed Central

Waithe, Dominic; Ferron, Laurent; Page, Karen M.; Chaggar, Kanchan; Dolphin, Annette C.

2011-01-01

The β-subunits of voltage-gated calcium channels regulate their functional expression and properties. Two mechanisms have been proposed for this, an effect on gating and an enhancement of expression. With respect to the effect on expression, β-subunits have been suggested to enhance trafficking by masking an unidentified endoplasmic reticulum (ER) retention signal. Here we have investigated whether, and how, β-subunits affect the level of CaV2.2 channels within somata and neurites of cultured sympathetic neurons. We have used YFP-CaV2.2 containing a mutation (W391A), that prevents binding of β-subunits to its I-II linker and found that expression of this channel was much reduced compared with WT CFP-CaV2.2 when both were expressed in the same neuron. This effect was particularly evident in neurites and growth cones. The difference between the levels of YFP-CaV2.2(W391A) and CFP-CaV2.2(WT) was lost in the absence of co-expressed β-subunits. Furthermore, the relative reduction of expression of CaV2.2(W391A) compared with the WT channel was reversed by exposure to two proteasome inhibitors, MG132 and lactacystin, particularly in the somata. In further experiments in tsA-201 cells, we found that proteasome inhibition did not augment the cell surface CaV2.2(W391A) level but resulted in the observation of increased ubiquitination, particularly of mutant channels. In contrast, we found no evidence for selective retention of CaV2.2(W391A) in the ER, in either the soma or growth cones. In conclusion, there is a marked effect of β-subunits on CaV2.2 expression, particularly in neurites, but our results point to protection from proteasomal degradation rather than masking of an ER retention signal. PMID:21233207

[Flight nurses' comprehension about their role in the multiprofesional team of aero-medical transport].

PubMed

Scuissiato, Dayane Reinhardt; Boffi, Letícia Valois; da Rocha, Roseline da Rocha; Montezeli, Juliana Helena; Bordin, Michelle Taverna; Peres, Aida Maris

2012-01-01

This is a descriptive qualitative research which aimed at identifying the flight nurses' comprehension by about their role in the aero-medical multiprofesional team. A semi-structured interview was carried out with eight flight nurses from Curitiba-PR, from June to August 2009. The speeches were analyzed by the content analysis, from which three categories emerged. The first describes the responsibilities of the flight nurses as managers of the aero-medical mission, planning for before, during and after the transport, what includes the aircraft check-list and knowledge of the patient's case. The second category deals with aspects of these professionals as care providers to the aero-transferred patient. The third describes communication and team-work as fundamental requirements for flight nurses. It was concluded that the nurse in aero-medical team mixes management and caring in his/her professional practice by the use of specific competences.

Structural basis for the differential effects of CaBP1 and calmodulin on Ca(V)1.2 calcium-dependent inactivation.

PubMed

Findeisen, Felix; Minor, Daniel L

2010-12-08

Calcium-binding protein 1 (CaBP1), a calmodulin (CaM) homolog, endows certain voltage-gated calcium channels (Ca(V)s) with unusual properties. CaBP1 inhibits Ca(V)1.2 calcium-dependent inactivation (CDI) and introduces calcium-dependent facilitation (CDF). Here, we show that the ability of CaBP1 to inhibit Ca(V)1.2 CDI and induce CDF arises from interaction between the CaBP1 N-lobe and interlobe linker residue Glu94. Unlike CaM, where functional EF hands are essential for channel modulation, CDI inhibition does not require functional CaBP1 EF hands. Furthermore, CaBP1-mediated CDF has different molecular requirements than CaM-mediated CDF. Overall, the data show that CaBP1 comprises two structural modules having separate functions: similar to CaM, the CaBP1 C-lobe serves as a high-affinity anchor that binds the Ca(V)1.2 IQ domain at a site that overlaps with the Ca²+/CaM C-lobe site, whereas the N-lobe/linker module houses the elements required for channel modulation. Discovery of this division provides the framework for understanding how CaBP1 regulates Ca(V)s. Copyright © 2010 Elsevier Ltd. All rights reserved.

Structural basis for the differential effects of CaBP1 and calmodulin on CaV1.2 calcium-dependent inactivation

PubMed Central

Findeisen, Felix; Minor, Daniel L.

2010-01-01

Calcium-binding protein 1 (CaBP1), a calmodulin (CaM) homolog, endows certain voltage-gated calcium channels (CaVs) with unusual properties. CaBP1 inhibits CaV1.2 calcium-dependent inactivation (CDI) and introduces calcium-dependent facilitation (CDF). Here, we show that the ability of CaBP1 to inhibit CaV1.2 CDI and induce CDF arises from interaction between the CaBP1 N-lobe and interlobe linker residue Glu94. Unlike CaM, where functional EF hands are essential for channel modulation, CDI inhibition does not require functional CaBP1 EF-hands. Furthermore, CaBP1-mediated CDF has different molecular requirements than CaM-mediated CDF. Overall, the data show that CaBP1 comprises two structural modules having separate functions: similar to CaM, the CaBP1 C-lobe serves as a high-affinity anchor that binds the CaV1.2 IQ domain at a site that overlaps with the Ca2+/CaM C-lobe site, whereas the N-lobe/linker module houses the elements required for channel modulation. Discovery of this division provides the framework for understanding how CaBP1 regulates CaVs. PMID:21134641

Aero-Thermal Calibration of the NASA Glenn Icing Research Tunnel (2012 Tests)

NASA Technical Reports Server (NTRS)

Pastor-Barsi, Christine; Allen, Arrington E.

2013-01-01

A full aero-thermal calibration of the NASA Glenn Icing Research Tunnel (IRT) was completed in 2012 following the major modifications to the facility that included replacement of the refrigeration plant and heat exchanger. The calibration test provided data used to fully document the aero-thermal flow quality in the IRT test section and to construct calibration curves for the operation of the IRT.

Search and Pursuit with Unmanned Aerial Vehicles in Road Networks

DTIC Science & Technology

2013-11-01

production volume in each area for use in consumer electronics. Simultaneously, a shift in defense strategy towards unmanned vehicles, particularly...Vöcking. Randomized pursuit-evasion in graphs. Combinatorics, Probability and Computing, 12:225–244, May 2003. [3] AeroVironment Inc. Raven Product Data...Ali and Mubarak Shah. COCOA - tracking in aerial imagery. In SPIE Airborne Intelligence, Surveillance, Reconnaissance Systems and Applications, 2006

Modulation of CaV2.1 channels by neuronal calcium sensor-1 induces short-term synaptic facilitation.

PubMed

Yan, Jin; Leal, Karina; Magupalli, Venkat G; Nanou, Evanthia; Martinez, Gilbert Q; Scheuer, Todd; Catterall, William A

2014-11-01

Facilitation and inactivation of P/Q-type Ca2+ currents mediated by Ca2+/calmodulin binding to Ca(V)2.1 channels contribute to facilitation and rapid depression of synaptic transmission, respectively. Other calcium sensor proteins displace calmodulin from its binding site and differentially modulate P/Q-type Ca2 + currents, resulting in diverse patterns of short-term synaptic plasticity. Neuronal calcium sensor-1 (NCS-1, frequenin) has been shown to enhance synaptic facilitation, but the underlying mechanism is unclear. We report here that NCS-1 directly interacts with IQ-like motif and calmodulin-binding domain in the C-terminal domain of Ca(V)2.1 channel. NCS-1 reduces Ca2 +-dependent inactivation of P/Q-type Ca2+ current through interaction with the IQ-like motif and calmodulin-binding domain without affecting peak current or activation kinetics. Expression of NCS-1 in presynaptic superior cervical ganglion neurons has no effect on synaptic transmission, eliminating effects of this calcium sensor protein on endogenous N-type Ca2+ currents and the endogenous neurotransmitter release machinery. However, in superior cervical ganglion neurons expressing wild-type Ca(V)2.1 channels, co-expression of NCS-1 induces facilitation of synaptic transmission in response to paired pulses and trains of depolarizing stimuli, and this effect is lost in Ca(V)2.1 channels with mutations in the IQ-like motif and calmodulin-binding domain. These results reveal that NCS-1 directly modulates Ca(V)2.1 channels to induce short-term synaptic facilitation and further demonstrate that CaS proteins are crucial in fine-tuning short-term synaptic plasticity.

Subthreshold pharmacological and genetic approaches to analyzing CaV2.1-mediated NMDA receptor signaling in short-term memory.

PubMed

Takahashi, Eiki; Niimi, Kimie; Itakura, Chitoshi

2010-10-25

Ca(V)2.1 is highly expressed in the nervous system and plays an essential role in the presynaptic modulation of neurotransmitter release machinery. Recently, the antiepileptic drug levetiracetam was reported to inhibit presynaptic Ca(V)2.1 functions, reducing glutamate release in the hippocampus, although the precise physiological role of Ca(V)2.1-regulated synaptic functions in cognitive performance at the system level remains unknown. This study examined whether Ca(V)2.1 mediates hippocampus-dependent spatial short-term memory using the object location and Y-maze tests, and perirhinal cortex-dependent nonspatial short-term memory using the object recognition test, via a combined pharmacological and genetic approach. Heterozygous rolling Nagoya (rol/+) mice carrying the Ca(V)2.1alpha(1) mutation had normal spatial and nonspatial short-term memory. A 100mg/kg dose of levetiracetam, which is ineffective in wild-type controls, blocked spatial short-term memory in rol/+ mice. At 5mg/kg, the N-methyl-D-aspartate (NMDA) receptor blocker (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), which is ineffective in wild-type controls, also blocked the spatial short-term memory in rol/+ mice. Furthermore, a combination of subthreshold doses of levetiracetam (25 mg/kg) and CPP (2.5mg/kg) triggered a spatial short-term memory deficit in rol/+ mice, but not in wild-type controls. Similar patterns of nonspatial short-term memory were observed in wild-type and rol/+ mice when injected with levetiracetam (0-300 mg/kg). These results indicate that Ca(V)2.1-mediated NMDA receptor signaling is critical in hippocampus-dependent spatial short-term memory and differs in various regions. The combination subthreshold pharmacological and genetic approach presented here is easily performed and can be used to study functional signaling pathways in neuronal circuits. Copyright © 2010 Elsevier B.V. All rights reserved.

76 FR 64795 - Airworthiness Directives; Sicma Aero Seat Passenger Seat Assemblies Installed on Various...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-19

... Airworthiness Directives; Sicma Aero Seat Passenger Seat Assemblies Installed on Various Transport Category..., 91xx, 92xx, 93xx, 95xx, and 96xx series passenger seat assemblies, installed on various transport... seat assemblies identified in Annex 1, Issue 2, dated March 19, 2004, of Sicma Aero Seat Service...

Sensitivity Analysis for Coupled Aero-structural Systems

NASA Technical Reports Server (NTRS)

Giunta, Anthony A.

1999-01-01

A novel method has been developed for calculating gradients of aerodynamic force and moment coefficients for an aeroelastic aircraft model. This method uses the Global Sensitivity Equations (GSE) to account for the aero-structural coupling, and a reduced-order modal analysis approach to condense the coupling bandwidth between the aerodynamic and structural models. Parallel computing is applied to reduce the computational expense of the numerous high fidelity aerodynamic analyses needed for the coupled aero-structural system. Good agreement is obtained between aerodynamic force and moment gradients computed with the GSE/modal analysis approach and the same quantities computed using brute-force, computationally expensive, finite difference approximations. A comparison between the computational expense of the GSE/modal analysis method and a pure finite difference approach is presented. These results show that the GSE/modal analysis approach is the more computationally efficient technique if sensitivity analysis is to be performed for two or more aircraft design parameters.

Multiple C-terminal tail Ca2+/CaMs regulate CaV1.2 function but do not mediate channel dimerization

PubMed Central

Kim, Eun Young; Rumpf, Christine H; Van Petegem, Filip; Arant, Ryan J; Findeisen, Felix; Cooley, Elizabeth S; Isacoff, Ehud Y; Minor, Daniel L

2010-01-01

Interactions between voltage-gated calcium channels (CaVs) and calmodulin (CaM) modulate CaV function. In this study, we report the structure of a Ca2+/CaM CaV1.2 C-terminal tail complex that contains two PreIQ helices bridged by two Ca2+/CaMs and two Ca2+/CaM–IQ domain complexes. Sedimentation equilibrium experiments establish that the complex has a 2:1 Ca2+/CaM:C-terminal tail stoichiometry and does not form higher order assemblies. Moreover, subunit-counting experiments demonstrate that in live cell membranes CaV1.2s are monomers. Thus, contrary to previous proposals, the crystallographic dimer lacks physiological relevance. Isothermal titration calorimetry and biochemical experiments show that the two Ca2+/CaMs in the complex have different properties. Ca2+/CaM bound to the PreIQ C-region is labile, whereas Ca2+/CaM bound to the IQ domain is not. Furthermore, neither of lobes of apo-CaM interacts strongly with the PreIQ domain. Electrophysiological studies indicate that the PreIQ C-region has a role in calcium-dependent facilitation. Together, the data show that two Ca2+/CaMs can bind the CaV1.2 tail simultaneously and indicate a functional role for Ca2+/CaM at the C-region site. PMID:20953164

Multiple C-terminal tail Ca(2+)/CaMs regulate Ca(V)1.2 function but do not mediate channel dimerization.

PubMed

Kim, Eun Young; Rumpf, Christine H; Van Petegem, Filip; Arant, Ryan J; Findeisen, Felix; Cooley, Elizabeth S; Isacoff, Ehud Y; Minor, Daniel L

2010-12-01

Interactions between voltage-gated calcium channels (Ca(V)s) and calmodulin (CaM) modulate Ca(V) function. In this study, we report the structure of a Ca(2+)/CaM Ca(V)1.2 C-terminal tail complex that contains two PreIQ helices bridged by two Ca(2+)/CaMs and two Ca(2+)/CaM-IQ domain complexes. Sedimentation equilibrium experiments establish that the complex has a 2:1 Ca(2+)/CaM:C-terminal tail stoichiometry and does not form higher order assemblies. Moreover, subunit-counting experiments demonstrate that in live cell membranes Ca(V)1.2s are monomers. Thus, contrary to previous proposals, the crystallographic dimer lacks physiological relevance. Isothermal titration calorimetry and biochemical experiments show that the two Ca(2+)/CaMs in the complex have different properties. Ca(2+)/CaM bound to the PreIQ C-region is labile, whereas Ca(2+)/CaM bound to the IQ domain is not. Furthermore, neither of lobes of apo-CaM interacts strongly with the PreIQ domain. Electrophysiological studies indicate that the PreIQ C-region has a role in calcium-dependent facilitation. Together, the data show that two Ca(2+)/CaMs can bind the Ca(V)1.2 tail simultaneously and indicate a functional role for Ca(2+)/CaM at the C-region site.

Small Satellites and the DARPA/Air Force Falcon Program

NASA Technical Reports Server (NTRS)

Weeks, David J.; Walker, Steven H.; Sackheim, Robert L.

2004-01-01

The FALCON ((Force Application and Launch from CONUS) program is a technology demonstration effort with three major components: a Small Launch Vehicle (SLV), a Common Aero Vehicle (CAV), and a Hypersonic Cruise Vehicle (HCV). Sponsored by DARPA and executed jointly by the United States Air Force and DARPA with NASA participation, the objectives are to develop and demonstrate technologies that will enable both near-term and far-term capability to execute time-critical, global reach missions. The focus of this paper is on the SLV as it relates to small satellites and the implications of lower cost to orbit for small satellites. The target recurring cost for placing 1000 pounds payloads into a circular reference orbit of 28.5 degrees at 100 nautical miles is $5,000,000 per launch. This includes range costs but not the payload or payload integration costs. In addition to the nominal 1000 pounds to LEO, FALCON is seeking delivery of a range of orbital payloads from 220 pounds to 2200 pounds to the reference orbit. Once placed on alert status, the SLV must be capable of launch within 24 hours.

Inhibitory gene expression of the Cav3.1 T-type calcium channel to improve neuronal injury induced by lidocaine hydrochloride.

PubMed

Wen, Xianjie; Xu, Shiyuan; Zhang, Qingguo; Li, Xiaohong; Liang, Hua; Yang, Chenxiang; Wang, Hanbing; Liu, Hongzhen

2016-03-15

Cav3.1 is a low-voltage-activated (LVA) calcium channel that plays a key role in regulating intracellular calcium ion levels. In this study, we observed the effects of lidocaine hydrochloride on the pshRNA-CACNA1G-SH-SY5Y cells that silenced Cav3.1 mRNA by RNA interference, and investigated the roles of p38 MAPK in these effects. We constructed the pNC-puro-CACNA1G-SH-SY5Y cells and pshRNA-CACNA1G -SH-SY5Y cells by the RNA interference. All the cells were cultured with or without 10mM lidocaine hydrochloride for 24 h. The cell morphology, cell viability, Cav3.1 and p38 protein expression, cell apoptosis rate and intracellular calcium ion concentration were detected. We found that all cells treated with 10mM lidocaine hydrochloride for 24 h showed cellular rounding, axonal regression, and cellular floating. Compared with the cells in SH-SY5Y+Lido group and NC+Lido group, those in the RNAi+Lido group showed similar changes, but of smaller magnitude. Additionally, following lidocaine hydrochloride all cells displayed increased Cav3.1 and p38 MAPK protein, apoptosis rate, and intracellular calcium ion levels; however,these changes in the RNAi+Lido group were less pronounced than in the SH-SY5Y+Lido and NC+Lido groups. The cell viability decreased following lidocaine hydrochloride treatment, but viability of the cells in the RNAi+Lido group was higher than in the SH-SY5Y+Lido and NC+Lido groups. The results showed that Cav3.1 may be involved in neuronal injury induced by lidocaine hydrochloride and that p38 MAPK phosphorylation was reduced upon Cav3.1 gene silencing. Copyright © 2016 Elsevier B.V. All rights reserved.

CAV-OX CAVITATION OXIDIATION PROCESS - MAGNUM WATER TECHNOLOGY, INC. - APPLICATIONS ANALYSIS REPORT

EPA Science Inventory

This report evaluates the ability of the CAV-OX cavitation oxidation process to remove volatile organic compounds (VOC) present in aqueous wastes. This report also presents economic data based on the Superfund Innovative Technology Evaluation (SITE) Program demonstration and nine...

Distinct transcriptomic changes in E14.5 mouse skeletal muscle lacking RYR1 or Cav1.1 converge at E18.5

PubMed Central

Henry, Margit; Rotshteyn, Tamara; Brunn, Anna; Carstov, Mariana; Deckert, Martina; Hescheler, Jürgen; Sachinidis, Agapios; Pfitzer, Gabriele

2018-01-01

In skeletal muscle the coordinated actions of two mechanically coupled Ca2+ channels—the 1,4-dihydropyridine receptor (Cav1.1) and the type 1 ryanodine receptor (RYR1)–underlie the molecular mechanism of rapid cytosolic [Ca2+] increase leading to contraction. While both [Ca2+]i and contractile activity have been implicated in the regulation of myogenesis, less is known about potential specific roles of Cav1.1 and RYR1 in skeletal muscle development. In this study, we analyzed the histology and the transcriptomic changes occurring at E14.5 –the end of primary myogenesis and around the onset of intrauterine limb movement, and at E18.5 –the end of secondary myogenesis, in WT, RYR1-/-, and Cav1.1-/- murine limb skeletal muscle. At E14.5 the muscle histology of both mutants exhibited initial alterations, which became much more severe at E18.5. Immunohistological analysis also revealed higher levels of activated caspase-3 in the Cav1.1-/- muscles at E14.5, indicating an increase in apoptosis. With WT littermates as controls, microarray analyses identified 61 and 97 differentially regulated genes (DEGs) at E14.5, and 493 and 1047 DEGs at E18.5, in RYR1-/- and Cav1.1-/- samples, respectively. Gene enrichment analysis detected no overlap in the affected biological processes and pathways in the two mutants at E14.5, whereas at E18.5 there was a significant overlap of DEGs in both mutants, affecting predominantly processes linked to muscle contraction. Moreover, the E18.5 vs. E14.5 comparison revealed multiple genotype-specific DEGs involved in contraction, cell cycle and miRNA-mediated signaling in WT, neuronal and bone development in RYR1-/-, and lipid metabolism in Cav1.1-/- samples. Taken together, our study reveals discrete changes in the global transcriptome occurring in limb skeletal muscle from E14.5 to E18.5 in WT, RYR1-/- and Cav1.1-/- mice. Our results suggest distinct functional roles for RYR1 and Cav1.1 in skeletal primary and secondary myogenesis. PMID

Two distinct voltage-sensing domains control voltage sensitivity and kinetics of current activation in CaV1.1 calcium channels.

PubMed

Tuluc, Petronel; Benedetti, Bruno; Coste de Bagneaux, Pierre; Grabner, Manfred; Flucher, Bernhard E

2016-06-01

Alternative splicing of the skeletal muscle CaV1.1 voltage-gated calcium channel gives rise to two channel variants with very different gating properties. The currents of both channels activate slowly; however, insertion of exon 29 in the adult splice variant CaV1.1a causes an ∼30-mV right shift in the voltage dependence of activation. Existing evidence suggests that the S3-S4 linker in repeat IV (containing exon 29) regulates voltage sensitivity in this voltage-sensing domain (VSD) by modulating interactions between the adjacent transmembrane segments IVS3 and IVS4. However, activation kinetics are thought to be determined by corresponding structures in repeat I. Here, we use patch-clamp analysis of dysgenic (CaV1.1 null) myotubes reconstituted with CaV1.1 mutants and chimeras to identify the specific roles of these regions in regulating channel gating properties. Using site-directed mutagenesis, we demonstrate that the structure and/or hydrophobicity of the IVS3-S4 linker is critical for regulating voltage sensitivity in the IV VSD, but by itself cannot modulate voltage sensitivity in the I VSD. Swapping sequence domains between the I and the IV VSDs reveals that IVS4 plus the IVS3-S4 linker is sufficient to confer CaV1.1a-like voltage dependence to the I VSD and that the IS3-S4 linker plus IS4 is sufficient to transfer CaV1.1e-like voltage dependence to the IV VSD. Any mismatch of transmembrane helices S3 and S4 from the I and IV VSDs causes a right shift of voltage sensitivity, indicating that regulation of voltage sensitivity by the IVS3-S4 linker requires specific interaction of IVS4 with its corresponding IVS3 segment. In contrast, slow current kinetics are perturbed by any heterologous sequences inserted into the I VSD and cannot be transferred by moving VSD I sequences to VSD IV. Thus, CaV1.1 calcium channels are organized in a modular manner, and control of voltage sensitivity and activation kinetics is accomplished by specific molecular mechanisms

Two distinct voltage-sensing domains control voltage sensitivity and kinetics of current activation in CaV1.1 calcium channels

PubMed Central

Tuluc, Petronel; Benedetti, Bruno; Coste de Bagneaux, Pierre; Grabner, Manfred

2016-01-01

Alternative splicing of the skeletal muscle CaV1.1 voltage-gated calcium channel gives rise to two channel variants with very different gating properties. The currents of both channels activate slowly; however, insertion of exon 29 in the adult splice variant CaV1.1a causes an ∼30-mV right shift in the voltage dependence of activation. Existing evidence suggests that the S3–S4 linker in repeat IV (containing exon 29) regulates voltage sensitivity in this voltage-sensing domain (VSD) by modulating interactions between the adjacent transmembrane segments IVS3 and IVS4. However, activation kinetics are thought to be determined by corresponding structures in repeat I. Here, we use patch-clamp analysis of dysgenic (CaV1.1 null) myotubes reconstituted with CaV1.1 mutants and chimeras to identify the specific roles of these regions in regulating channel gating properties. Using site-directed mutagenesis, we demonstrate that the structure and/or hydrophobicity of the IVS3–S4 linker is critical for regulating voltage sensitivity in the IV VSD, but by itself cannot modulate voltage sensitivity in the I VSD. Swapping sequence domains between the I and the IV VSDs reveals that IVS4 plus the IVS3–S4 linker is sufficient to confer CaV1.1a-like voltage dependence to the I VSD and that the IS3–S4 linker plus IS4 is sufficient to transfer CaV1.1e-like voltage dependence to the IV VSD. Any mismatch of transmembrane helices S3 and S4 from the I and IV VSDs causes a right shift of voltage sensitivity, indicating that regulation of voltage sensitivity by the IVS3–S4 linker requires specific interaction of IVS4 with its corresponding IVS3 segment. In contrast, slow current kinetics are perturbed by any heterologous sequences inserted into the I VSD and cannot be transferred by moving VSD I sequences to VSD IV. Thus, CaV1.1 calcium channels are organized in a modular manner, and control of voltage sensitivity and activation kinetics is accomplished by specific molecular

CaV 3.1 and CaV 3.3 account for T-type Ca2+ current in GH3 cells.

PubMed

Mudado, M A; Rodrigues, A L; Prado, V F; Beirão, P S L; Cruz, J S

2004-06-01

T-type Ca2+ channels are important for cell signaling by a variety of cells. We report here the electrophysiological and molecular characteristics of the whole-cell Ca2+ current in GH3 clonal pituitary cells. The current inactivation at 0 mV was described by a single exponential function with a time constant of 18.32 +/- 1.87 ms (N = 16). The I-V relationship measured with Ca2+ as a charge carrier was shifted to the left when we applied a conditioning pre-pulse of up to -120 mV, indicating that a low voltage-activated current may be present in GH3 cells. Transient currents were first activated at -50 mV and peaked around -20 mV. The half-maximal voltage activation and the slope factors for the two conditions are -35.02 +/- 2.4 and 6.7 +/- 0.3 mV (pre-pulse of -120 mV, N = 15), and -27.0 +/- 0.97 and 7.5 +/- 0.7 mV (pre-pulse of -40 mV, N = 9). The 8-mV shift in the activation mid-point was statistically significant (P < 0.05). The tail currents decayed bi-exponentially suggesting two different T-type Ca2+ channel populations. RT-PCR revealed the presence of alpha1G (CaV3.1) and alpha1I (CaV3.3) T-type Ca2+ channel mRNA transcripts.

Chemical composition and evaluation of antinociceptive activity of the essential oil of Stevia serrata Cav. from Guatemala.

PubMed

Reis Simas, Daniel Luiz; Mérida-Reyes, Max Samuel; Muñoz-Wug, Manuel Alejandro; Cordeiro, Millena Santos; Giorno, Thais Biondino Sardella; Taracena, Edwin Adolfo; Oliva-Hernández, Bessie Evelyn; Martínez-Arévalo, José Vicente; Fernandes, Patricia Dias; Pérez-Sabino, Juan Francisco; Jorge Ribeiro da Silva, Antonio

2017-11-13

The composition and the antinociceptive activity of the essential oil of Stevia serrata Cav. from a population located in the west highlands of Guatemala were evaluated. A yield of 0.2% (w/w) of essential oil was obtained by hydrodistillation of the dried aerial parts of the plant. The essential oil analysed by GC-FID and GC-MS showed a high content of sesquiterpenoids, with chamazulene (60.1%) as the major component and 91.5% of the essential oil composition was identified. To evaluate antinociceptive activity in mice, the essential oil of S. serrata Cav. was administered as gavage, using three different doses. In the formalin test, the animals were pre-treated with oral doses of the essential oil before the administration of formalin. Oral administration of S. serrata Cav. essential oil produced a marked antinociceptive activity. Therefore, the plant could be domesticated as a source of essential oil rich in chamazulene for developing medicinal products.

PIP₂ hydrolysis is responsible for voltage independent inhibition of CaV2.2 channels in sympathetic neurons.

PubMed

Vivas, Oscar; Castro, Hector; Arenas, Isabel; Elías-Viñas, David; García, David E

2013-03-08

GPCRs regulate Ca(V)2.2 channels through both voltage dependent and independent inhibition pathways. The aim of the present work was to assess the phosphatidylinositol-4,5-bisphosphate (PIP2) as the molecule underlying the voltage independent inhibition of Ca(V)2.2 channels in SCG neurons. We used a double pulse protocol to study the voltage independent inhibition and changed the PIP(2) concentration by means of blocking the enzyme PLC, filling the cell with a PIP(2) analogue and preventing the PIP(2) resynthesis with wortmannin. We found that voltage independent inhibition requires the activation of PLC and can be hampered by internal dialysis of exogenous PIP(2). In addition, the recovery from voltage independent inhibition is blocked by inhibition of the enzymes involved in the resynthesis of PIP(2). These results support that the hydrolysis of PIP(2) is responsible for the voltage independent inhibition of Ca(V)2.2 channels. Copyright © 2013 Elsevier Inc. All rights reserved.

CFD-based aero-optical analysis of flow fields over two-dimensional cavities with active flow control

NASA Astrophysics Data System (ADS)

Tan, Yan

Prediction and control of optical wave front distortions and aberrations in a high energy laser beam due to interaction with an unsteady highly non-uniform flow field is of great importance in the development of directed energy weapon systems for Unmanned Air Vehicles (UAV). The unsteady shear layer over the weapons bay cavity is the primary cause of this distortion of the optical wave front. The large scale vortical structure of the shear layer over the cavity can be significantly reduced by employing an active flow control technique combined with passive flow control. This dissertation explores various active and passive control methods to suppress the cavity oscillations and thereby improve the aero-optics of cavity flow. In active flow control technique, a steady or a pulsed jet is applied at the sharp leading edge of cavities of different aspect ratios L/D (=2, 4, 15), where L and D are the width and the depth of a cavity respectively. In the passive flow control approach, the sharp leading or trailing edge of the cavity is modified into a round edge of different radii. Both of these active and passive flow control approaches are studied independently and in combination. Numerical simulations are performed, with and without active flow control for subsonic free stream flow past two-dimensional sharp and round leading or trailing edge cavities using Unsteady Reynolds-Averaged Navier-Stokes (URANS) equations with a two-equation Shear Stress Transport (SST) turbulence model or a hybrid SST/Large Eddy Simulation (LES) model. Aero-optical analysis is developed and applied to all the simulation cases. Index of refraction and Optical Path Difference (OPD) are compared for flow fields without and with active flow control. Root-Mean-Square (RMS) value of OPD is calculated and compared with the experimental data, where available. The effect of steady and pulsed blowing on buffet loading on the downstream face of the cavity is also computed. Using the numerical

Roles of Ca(v) channels and AHNAK1 in T cells: the beauty and the beast.

PubMed

Matza, Didi; Flavell, Richard A

2009-09-01

T lymphocytes require Ca2+ entry though the plasma membrane for their activation and function. Recently, several routes for Ca2+ entry through the T-cell plasma membrane after activation have been described. These include calcium release-activated channels (CRAC), transient receptor potential (TRP) channels, and inositol-1,4,5-trisphosphate receptors (IP3Rs). Herein we review the emergence of a fourth new route for Ca2+ entry, composed of Ca(v) channels (also known as L-type voltage-gated calcium channels) and the scaffold protein AHNAK1 (AHNAK/desmoyokin). Both helper (CD4+) and killer (CD8+) T cells express high levels of Ca(v)1 alpha1 subunits (alpha1S, alpha1C, alpha1D, and alpha1F) and AHNAK1 after their differentiation and require these molecules for Ca2+ entry during an immune response. In this article, we describe the observations and open questions that ultimately suggest the involvement of multiple consecutive routes for Ca2+ entry into lymphocytes, one of which may be mediated by Ca(v) channels and AHNAK1.

Altered short-term synaptic plasticity and reduced muscle strength in mice with impaired regulation of presynaptic CaV2.1 Ca2+ channels

PubMed Central

Nanou, Evanthia; Yan, Jin; Whitehead, Nicholas P.; Kim, Min Jeong; Froehner, Stanley C.; Scheuer, Todd; Catterall, William A.

2016-01-01

Facilitation and inactivation of P/Q-type calcium (Ca2+) currents through the regulation of voltage-gated Ca2+ (CaV) 2.1 channels by Ca2+ sensor (CaS) proteins contributes to the facilitation and rapid depression of synaptic transmission in cultured neurons that transiently express CaV2.1 channels. To examine the modulation of endogenous CaV2.1 channels by CaS proteins in native synapses, we introduced a mutation (IM-AA) into the CaS protein-binding site in the C-terminal domain of CaV2.1 channels in mice, and tested synaptic facilitation and depression in neuromuscular junction synapses that use exclusively CaV2.1 channels for Ca2+ entry that triggers synaptic transmission. Even though basal synaptic transmission was unaltered in the neuromuscular synapses in IM-AA mice, we found reduced short-term facilitation in response to paired stimuli at short interstimulus intervals in IM-AA synapses. In response to trains of action potentials, we found increased facilitation at lower frequencies (10–30 Hz) in IM-AA synapses accompanied by slowed synaptic depression, whereas synaptic facilitation was reduced at high stimulus frequencies (50–100 Hz) that would induce strong muscle contraction. As a consequence of altered regulation of CaV2.1 channels, the hindlimb tibialis anterior muscle in IM-AA mice exhibited reduced peak force in response to 50 Hz stimulation and increased muscle fatigue. The IM-AA mice also had impaired motor control, exercise capacity, and grip strength. Taken together, our results indicate that regulation of CaV2.1 channels by CaS proteins is essential for normal synaptic plasticity at the neuromuscular junction and for muscle strength, endurance, and motor coordination in mice in vivo. PMID:26755585

AERO: A Decision Support Tool for Wind Erosion Assessment in Rangelands and Croplands

NASA Astrophysics Data System (ADS)

Galloza, M.; Webb, N.; Herrick, J.

2015-12-01

Wind erosion is a key driver of global land degradation, with on- and off-site impacts on agricultural production, air quality, ecosystem services and climate. Measuring rates of wind erosion and dust emission across land use and land cover types is important for quantifying the impacts and identifying and testing practical management options. This process can be assisted by the application of predictive models, which can be a powerful tool for land management agencies. The Aeolian EROsion (AERO) model, a wind erosion and dust emission model interface provides access by non-expert land managers to a sophisticated wind erosion decision-support tool. AERO incorporates land surface processes and sediment transport equations from existing wind erosion models and was designed for application with available national long-term monitoring datasets (e.g. USDI BLM Assessment, Inventory and Monitoring, USDA NRCS Natural Resources Inventory) and monitoring protocols. Ongoing AERO model calibration and validation are supported by geographically diverse data on wind erosion rates and land surface conditions collected by the new National Wind Erosion Research Network. Here we present the new AERO interface, describe parameterization of the underpinning wind erosion model, and provide a summary of the model applications across agricultural lands and rangelands in the United States.

Contribution of S4 segments and S4-S5 linkers to the low-voltage activation properties of T-type CaV3.3 channels.

PubMed

Sanchez-Sandoval, Ana Laura; Herrera Carrillo, Zazil; Díaz Velásquez, Clara Estela; Delgadillo, Dulce María; Rivera, Heriberto Manuel; Gomora, Juan Carlos

2018-01-01

Voltage-gated calcium channels contain four highly conserved transmembrane helices known as S4 segments that exhibit a positively charged residue every third position, and play the role of voltage sensing. Nonetheless, the activation range between high-voltage (HVA) and low-voltage (LVA) activated calcium channels is around 30-40 mV apart, despite the high level of amino acid similarity within their S4 segments. To investigate the contribution of S4 voltage sensors for the low-voltage activation characteristics of CaV3.3 channels we constructed chimeras by swapping S4 segments between this LVA channel and the HVA CaV1.2 channel. The substitution of S4 segment of Domain II in CaV3.3 by that of CaV1.2 (chimera IIS4C) induced a ~35 mV shift in the voltage-dependence of activation towards positive potentials, showing an I-V curve that almost overlaps with that of CaV1.2 channel. This HVA behavior induced by IIS4C chimera was accompanied by a 2-fold decrease in the voltage-dependence of channel gating. The IVS4 segment had also a strong effect in the voltage sensing of activation, while substitution of segments IS4 and IIIS4 moved the activation curve of CaV3.3 to more negative potentials. Swapping of IIS4 voltage sensor influenced additional properties of this channel such as steady-state inactivation, current decay, and deactivation. Notably, Domain I voltage sensor played a major role in preventing CaV3.3 channels to inactivate from closed states at extreme hyperpolarized potentials. Finally, site-directed mutagenesis in the CaV3.3 channel revealed a partial contribution of the S4-S5 linker of Domain II to LVA behavior, with synergic effects observed in double and triple mutations. These findings indicate that IIS4 and, to a lesser degree IVS4, voltage sensors are crucial in determining the LVA properties of CaV3.3 channels, although the accomplishment of this function involves the participation of other structural elements like S4-S5 linkers.

Contribution of S4 segments and S4-S5 linkers to the low-voltage activation properties of T-type CaV3.3 channels

PubMed Central

Sanchez-Sandoval, Ana Laura; Herrera Carrillo, Zazil; Díaz Velásquez, Clara Estela; Delgadillo, Dulce María; Rivera, Heriberto Manuel

2018-01-01

Voltage-gated calcium channels contain four highly conserved transmembrane helices known as S4 segments that exhibit a positively charged residue every third position, and play the role of voltage sensing. Nonetheless, the activation range between high-voltage (HVA) and low-voltage (LVA) activated calcium channels is around 30–40 mV apart, despite the high level of amino acid similarity within their S4 segments. To investigate the contribution of S4 voltage sensors for the low-voltage activation characteristics of CaV3.3 channels we constructed chimeras by swapping S4 segments between this LVA channel and the HVA CaV1.2 channel. The substitution of S4 segment of Domain II in CaV3.3 by that of CaV1.2 (chimera IIS4C) induced a ~35 mV shift in the voltage-dependence of activation towards positive potentials, showing an I-V curve that almost overlaps with that of CaV1.2 channel. This HVA behavior induced by IIS4C chimera was accompanied by a 2-fold decrease in the voltage-dependence of channel gating. The IVS4 segment had also a strong effect in the voltage sensing of activation, while substitution of segments IS4 and IIIS4 moved the activation curve of CaV3.3 to more negative potentials. Swapping of IIS4 voltage sensor influenced additional properties of this channel such as steady-state inactivation, current decay, and deactivation. Notably, Domain I voltage sensor played a major role in preventing CaV3.3 channels to inactivate from closed states at extreme hyperpolarized potentials. Finally, site-directed mutagenesis in the CaV3.3 channel revealed a partial contribution of the S4-S5 linker of Domain II to LVA behavior, with synergic effects observed in double and triple mutations. These findings indicate that IIS4 and, to a lesser degree IVS4, voltage sensors are crucial in determining the LVA properties of CaV3.3 channels, although the accomplishment of this function involves the participation of other structural elements like S4-S5 linkers. PMID:29474447

Global Mobile Satellite Service Interference Analysis for the AeroMACS

NASA Technical Reports Server (NTRS)

Wilson, Jeffrey D.; Apaza, Rafael D.; Hall, Ward; Phillips, Brent

2013-01-01

The AeroMACS (Aeronautical Mobile Airport Communications System), which is based on the IEEE 802.16-2009 mobile wireless standard, is envisioned as the wireless network which will cover all areas of airport surfaces for next generation air transportation. It is expected to be implemented in the 5091-5150 MHz frequency band which is also occupied by mobile satellite service uplinks. Thus the AeroMACS must be designed to avoid interference with this incumbent service. Simulations using Visualyse software were performed utilizing a global database of 6207 airports. Variations in base station and subscriber antenna distribution and gain pattern were examined. Based on these simulations, recommendations for global airport base station and subscriber antenna power transmission limitations are provided.

The stargazin-related protein γ7 interacts with the mRNA binding protein hnRNP A2 and regulates the stability of specific mRNAs including CaV2.2

PubMed Central

Ferron, Laurent; Davies, Anthony; Page, Karen M.; Cox, David J.; Leroy, Jerôme; Waithe, Dominic; Butcher, Adrian J.; Sellaturay, Priya; Bolsover, Steven; Pratt, Wendy S.; Moss, Fraser J.; Dolphin, Annette C.

2009-01-01

The role(s) of the novel stargazin-like γ-subunit proteins remain controversial. We have shown previously that the neuron-specific γ7 suppresses the expression of certain calcium channels, particularly CaV2.2, and is therefore unlikely to operate as a calcium channel subunit. We now show that the effect of γ7 on CaV2.2 expression is via an increase in the degradation rate of CaV2.2 mRNA, and hence a reduction of CaV2.2 protein level. Furthermore, exogenous expression of γ7 in PC12 cells also decreased the endogenous CaV2.2 mRNA level. Conversely, knockdown of endogenous γ7 with short-hairpin RNAs produced a reciprocal enhancement of CaV2.2 mRNA stability and an increase in endogenous calcium currents in PC12 cells. Moreover, both endogenous and expressed γ7 are present on intracellular membranes, rather than the plasma membrane. The cytoplasmic C-terminus of γ7 is essential for all its effects, and we show that γ7 binds directly via its C-terminus to a ribonucleoprotein (hnRNP A2), which also binds to a motif in CaV2.2 mRNA, and is associated with native CaV2.2 mRNA in PC12 cells. The expression of hnRNP A2 enhances CaV2.2 IBa and this enhancement is prevented by a concentration of γ7 that alone has no effect on IBa. The effect of γ7 is selective for certain mRNAs as it had no effect on α2δ-2 mRNA stability, but it decreased the mRNA stability for the potassium-chloride co-transporter, KCC1, which contains a similar hnRNP A2 binding motif to that in CaV2.2 mRNA. Our results indicate that γ7 plays a role in stabilizing CaV2.2 mRNA. PMID:18923037

Aero-optics overview. [laser applications

NASA Technical Reports Server (NTRS)

Gilbert, K. G.

1980-01-01

Various aero-optical phenomena are discussed with reference to their effect on airborne high energy lasers. Major emphasis is placed on: compressibility effects induced in the surrounding flow field; viscous effects which manifests themselves as aircraft boundary layers or shear layers; inviscid flow fields surrounding the aircraft due to airflow around protuberance such as laser turret assemblies; and shocks, established whenever local flow exceeds Mach one. The significant physical parameters affecting the interaction of a laser beam with a turbulent boundary layer are also described.

Altered Cav1.2 function in the Timothy syndrome mouse model produces ascending serotonergic abnormalities.

PubMed

Ehlinger, Daniel G; Commons, Kathryn G

2017-10-01

Polymorphism in the gene CACNA1C, encoding the pore-forming subunit of Cav1.2 L-type calcium channels, has one of the strongest genetic linkages to schizophrenia, bipolar disorder and major depressive disorder: psychopathologies in which serotonin signaling has been implicated. Additionally, a gain-of-function mutation in CACNA1C is responsible for the neurodevelopmental disorder Timothy syndrome that presents with prominent behavioral features on the autism spectrum. Given an emerging role for serotonin in the etiology of autism spectrum disorders (ASD), we investigate the relationship between Cav1.2 and the ascending serotonin system in the Timothy syndrome type 2 (TS2-neo) mouse, which displays behavioral features consistent with the core triad of ASD. We find that TS2-neo mice exhibit enhanced serotonin tissue content and axon innervation of the dorsal striatum, as well as decreased serotonin turnover in the amygdala. These regionally specific alterations are accompanied by an enhanced active coping response during acute stress (forced swim), serotonin neuron Fos activity in the caudal dorsal raphe, and serotonin type 1A receptor-dependent feedback inhibition of the rostral dorsal raphe nuclei. Collectively, these results suggest that the global gain-of-function Cav1.2 mutation associated with Timothy syndrome has pleiotropic effects on the ascending serotonin system including neuroanatomical changes, regional differences in forebrain serotonin metabolism and feedback regulatory control mechanisms within the dorsal raphe. Altered activity of the ascending serotonin system continues to emerge as a common neural signature across several ASD mouse models, and the capacity for Cav1.2 L-type calcium channels to impact both serotonin structure and function has important implications for several neuropsychiatric conditions. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

CAV3 mutations causing exercise intolerance, myalgia and rhabdomyolysis: Expanding the phenotypic spectrum of caveolinopathies.

PubMed

Scalco, Renata Siciliani; Gardiner, Alice R; Pitceathly, Robert D S; Hilton-Jones, David; Schapira, Anthony H; Turner, Chris; Parton, Matt; Desikan, Mahalekshmi; Barresi, Rita; Marsh, Julie; Manzur, Adnan Y; Childs, Anne-Marie; Feng, Lucy; Murphy, Elaine; Lamont, Phillipa J; Ravenscroft, Gianina; Wallefeld, William; Davis, Mark R; Laing, Nigel G; Holton, Janice L; Fialho, Doreen; Bushby, Kate; Hanna, Michael G; Phadke, Rahul; Jungbluth, Heinz; Houlden, Henry; Quinlivan, Ros

2016-08-01

Rhabdomyolysis is often due to a combination of environmental trigger(s) and genetic predisposition; however, the underlying genetic cause remains elusive in many cases. Mutations in CAV3 lead to various neuromuscular phenotypes with partial overlap, including limb girdle muscular dystrophy type 1C (LGMD1C), rippling muscle disease, distal myopathy and isolated hyperCKemia. Here we present a series of eight patients from seven families presenting with exercise intolerance and rhabdomyolysis caused by mutations in CAV3 diagnosed by next generation sequencing (NGS) (n = 6). Symptoms included myalgia (n = 7), exercise intolerance (n = 7) and episodes of rhabdomyolysis (n = 2). Percussion-induced rapid muscle contractions (PIRCs) were seen in five out of six patients examined. A previously reported heterozygous mutation in CAV3 (p.T78M) and three novel variants (p.V14I, p.F41S, p.F54V) were identified. Caveolin-3 immunolabeling in muscle was normal in 3/4 patients; however, immunoblotting showed more than 50% reduction of caveolin-3 in five patients compared with controls. This case series demonstrates that exercise intolerance, myalgia and rhabdomyolysis may be caused by CAV3 mutations and broadens the phenotypic spectrum of caveolinopathies. In our series, immunoblotting was a more sensitive method to detect reduced caveolin-3 levels than immunohistochemistry in skeletal muscle. Patients presenting with muscle pain, exercise intolerance and rhabdomyolysis should be routinely tested for PIRCs as this may be an important clinical clue for caveolinopathies, even in the absence of other "typical" features. The use of NGS may expand current knowledge concerning inherited diseases, and unexpected/atypical phenotypes may be attributed to well-known human disease genes. Copyright © 2016 Elsevier B.V. All rights reserved.

Coexpression of high-voltage-activated ion channels Kv3.4 and Cav1.2 in pioneer axons during pathfinding in the developing rat forebrain.

PubMed

Huang, Chia-Yi; Chu, Dachen; Hwang, Wei-Chao; Tsaur, Meei-Ling

2012-11-01

Precise axon pathfinding is crucial for establishment of the initial neuronal network during development. Pioneer axons navigate without the help of preexisting axons and pave the way for follower axons that project later. Voltage-gated ion channels make up the intrinsic electrical activity of pioneer axons and regulate axon pathfinding. To elucidate which channel molecules are present in pioneer axons, immunohistochemical analysis was performed to examine 14 voltage-gated ion channels (Kv1.1-Kv1.3, Kv3.1-Kv3.4, Kv4.3, Cav1.2, Cav1.3, Cav2.2, Nav1.2, Nav1.6, and Nav1.9) in nine axonal tracts in the developing rat forebrain, including the optic nerve, corpus callosum, corticofugal fibers, thalamocortical axons, lateral olfactory tract, hippocamposeptal projection, anterior commissure, hippocampal commissure, and medial longitudinal fasciculus. We found A-type K⁺ channel Kv3.4 in both pioneer axons and early follower axons and L-type Ca²⁺ channel Cav1.2 in pioneer axons and early and late follower axons. Spatially, Kv3.4 and Cav1.2 were colocalized with markers of pioneer neurons and pioneer axons, such as deleted in colorectal cancer (DCC), in most fiber tracts examined. Temporally, Kv3.4 and Cav1.2 were expressed abundantly in most fiber tracts during axon pathfinding but were downregulated beginning in synaptogenesis. By contrast, delayed rectifier Kv channels (e.g., Kv1.1) and Nav channels (e.g., Nav1.2) were absent from these fiber tracts (except for the corpus callosum) during pathfinding of pioneer axons. These data suggest that Kv3.4 and Cav1.2, two high-voltage-activated ion channels, may act together to control Ca²⁺ -dependent electrical activity of pioneer axons and play important roles during axon pathfinding. Copyright © 2012 Wiley Periodicals, Inc.

Regulation of CaV2 calcium channels by G protein coupled receptors

PubMed Central

Zamponi, Gerald W.; Currie, Kevin P.M.

2012-01-01

Voltage gated calcium channels (Ca2+ channels) are key mediators of depolarization induced calcium influx into excitable cells, and thereby play pivotal roles in a wide array of physiological responses. This review focuses on the inhibition of CaV2 (N- and P/Q-type) Ca2+-channels by G protein coupled receptors (GPCRs), which exerts important autocrine/paracrine control over synaptic transmission and neuroendocrine secretion. Voltage-dependent inhibition is the most widespread mechanism, and involves direct binding of the G protein βγ dimer (Gβγ) to the α1 subunit of CaV2 channels. GPCRs can also recruit several other distinct mechanisms including phosphorylation, lipid signaling pathways, and channel trafficking that result in voltage-independent inhibition. Current knowledge of Gβγ-mediated inhibition is reviewed, including the molecular interactions involved, determinants of voltage-dependence, and crosstalk with other cell signaling pathways. A summary of recent developments in understanding the voltage-independent mechanisms prominent in sympathetic and sensory neurons is also included. PMID:23063655

Ca2+-independent Activation of Ca2+/Calmodulin-dependent Protein Kinase II Bound to the C-terminal Domain of CaV2.1 Calcium Channels*

PubMed Central

Magupalli, Venkat G.; Mochida, Sumiko; Yan, Jin; Jiang, Xin; Westenbroek, Ruth E.; Nairn, Angus C.; Scheuer, Todd; Catterall, William A.

2013-01-01

Ca2+/calmodulin-dependent protein kinase II (CaMKII) forms a major component of the postsynaptic density where its functions in synaptic plasticity are well established, but its presynaptic actions are poorly defined. Here we show that CaMKII binds directly to the C-terminal domain of CaV2.1 channels. Binding is enhanced by autophosphorylation, and the kinase-channel signaling complex persists after dephosphorylation and removal of the Ca2+/CaM stimulus. Autophosphorylated CaMKII can bind the CaV2.1 channel and synapsin-1 simultaneously. CaMKII binding to CaV2.1 channels induces Ca2+-independent activity of the kinase, which phosphorylates the enzyme itself as well as the neuronal substrate synapsin-1. Facilitation and inactivation of CaV2.1 channels by binding of Ca2+/CaM mediates short term synaptic plasticity in transfected superior cervical ganglion neurons, and these regulatory effects are prevented by a competing peptide and the endogenous brain inhibitor CaMKIIN, which blocks binding of CaMKII to CaV2.1 channels. These results define the functional properties of a signaling complex of CaMKII and CaV2.1 channels in which both binding partners are persistently activated by their association, and they further suggest that this complex is important in presynaptic terminals in regulating protein phosphorylation and short term synaptic plasticity. PMID:23255606

Conditional Deletion of the L-Type Calcium Channel Cav1.2 in NG2-Positive Cells Impairs Remyelination in Mice.

PubMed

Santiago González, Diara A; Cheli, Veronica T; Zamora, Norma N; Lama, Tenzing N; Spreuer, Vilma; Murphy, Geoffrey G; Paez, Pablo M

2017-10-18

Exploring the molecular mechanisms that drive the maturation of oligodendrocyte progenitor cells (OPCs) during the remyelination process is essential to developing new therapeutic tools to intervene in demyelinating diseases such as multiple sclerosis. To determine whether L-type voltage-gated calcium channels (L-VGCCs) are required for OPC development during remyelination, we generated an inducible conditional knock-out mouse in which the L-VGCC isoform Cav1.2 was deleted in NG2-positive OPCs (Cav1.2 KO ). Using the cuprizone (CPZ) model of demyelination and mice of either sex, we establish that Cav1.2 deletion in OPCs leads to less efficient remyelination of the adult brain. Specifically, Cav1.2 KO OPCs mature slower and produce less myelin than control oligodendrocytes during the recovery period after CPZ intoxication. This reduced remyelination was accompanied by an important decline in the number of myelinating oligodendrocytes and in the rate of OPC proliferation. Furthermore, during the remyelination phase of the CPZ model, the corpus callosum of Cav1.2 KO animals presented a significant decrease in the percentage of myelinated axons and a substantial increase in the mean g-ratio of myelinated axons compared with controls. In addition, in a mouse line in which the Cav1.2 KO OPCs were identified by a Cre reporter, we establish that Cav1.2 KO OPCs display a reduced maturational rate through the entire remyelination process. These results suggest that Ca 2+ influx mediated by L-VGCCs in oligodendroglial cells is necessary for normal remyelination and is an essential Ca 2+ channel for OPC maturation during the remyelination of the adult brain. SIGNIFICANCE STATEMENT Ion channels implicated in oligodendrocyte differentiation and maturation may induce positive signals for myelin recovery. Voltage-gated Ca 2+ channels (VGCCs) are important for normal myelination by acting at several critical steps during oligodendrocyte progenitor cell (OPC) development. To

Phosphorylation sites in the Hook domain of CaVβ subunits differentially modulate CaV1.2 channel function.

PubMed

Brunet, Sylvain; Emrick, Michelle A; Sadilek, Martin; Scheuer, Todd; Catterall, William A

2015-10-01

Regulation of L-type calcium current is critical for the development, function, and regulation of many cell types. Ca(V)1.2 channels that conduct L-type calcium currents are regulated by many protein kinases, but the sites of action of these kinases remain unknown in most cases. We combined mass spectrometry (LC-MS/MS) and whole-cell patch clamp techniques in order to identify sites of phosphorylation of Ca(V)β subunits in vivo and test the impact of mutations of those sites on Ca(V)1.2 channel function in vitro. Using the Ca(V)1.1 channel purified from rabbit skeletal muscle as a substrate for phosphoproteomic analysis, we found that Ser(193) and Thr(205) in the HOOK domain of Ca(V)β1a subunits were both phosphorylated in vivo. Ser(193) is located in a potential consensus sequence for casein kinase II, but it was not phosphorylated in vitro by that kinase. In contrast, Thr(205) is located in a consensus sequence for cAMP-dependent phosphorylation, and it was robustly phosphorylated in vitro by PKA. These two sites are conserved in multiple Ca(V)β subunit isoforms, including the principal Ca(V)β subunit of cardiac Ca(V)1.2 channels, Ca(V)β2b. In order to assess potential modulatory effects of phosphorylation at these sites separately from the effects of phosphorylation of the α11.2 subunit, we inserted phosphomimetic or phosphoinhibitory mutations in Ca(V)β2b and analyzed their effects on Ca(V)1.2 channel function in transfected nonmuscle cells. The phosphomimetic mutation Ca(V)β2b(S152E) decreased peak channel currents and shifted the voltage dependence of both activation and inactivation to more positive membrane potentials. The phosphoinhibitory mutation Ca(V)β2b(S152A) had opposite effects. There were no differences in peak Ca(V)1.2 currents or voltage dependence between the phosphomimetic mutation Ca(V)β2b(T164D) and the phosphoinhibitory mutation Ca(V)β2b(T164A). However, calcium-dependent inactivation was significantly increased for the

Compensatory T-type Ca2+ channel activity alters D2-autoreceptor responses of Substantia nigra dopamine neurons from Cav1.3 L-type Ca2+ channel KO mice.

PubMed

Poetschke, Christina; Dragicevic, Elena; Duda, Johanna; Benkert, Julia; Dougalis, Antonios; DeZio, Roberta; Snutch, Terrance P; Striessnig, Joerg; Liss, Birgit

2015-09-18

The preferential degeneration of Substantia nigra dopamine midbrain neurons (SN DA) causes the motor-symptoms of Parkinson's disease (PD). Voltage-gated L-type calcium channels (LTCCs), especially the Cav1.3-subtype, generate an activity-related oscillatory Ca(2+) burden in SN DA neurons, contributing to their degeneration and PD. While LTCC-blockers are already in clinical trials as PD-therapy, age-dependent functional roles of Cav1.3 LTCCs in SN DA neurons remain unclear. Thus, we analysed juvenile and adult Cav1.3-deficient mice with electrophysiological and molecular techniques. To unmask compensatory effects, we compared Cav1.3 KO mice with pharmacological LTCC-inhibition. LTCC-function was not necessary for SN DA pacemaker-activity at either age, but rather contributed to their pacemaker-precision. Moreover, juvenile Cav1.3 KO but not WT mice displayed adult wildtype-like, sensitised inhibitory dopamine-D2-autoreceptor (D2-AR) responses that depended upon both, interaction of the neuronal calcium sensor NCS-1 with D2-ARs, and on voltage-gated T-type calcium channel (TTCC) activity. This functional KO-phenotype was accompanied by cell-specific up-regulation of NCS-1 and Cav3.1-TTCC mRNA. Furthermore, in wildtype we identified an age-dependent switch of TTCC-function from contributing to SN DA pacemaker-precision in juveniles to pacemaker-frequency in adults. This novel interplay of Cav1.3 L-type and Cav3.1 T-type channels, and their modulation of SN DA activity-pattern and D2-AR-sensitisation, provide new insights into flexible age- and calcium-dependent activity-control of SN DA neurons and its pharmacological modulation.

Spinocerebellar ataxia type 6 knockin mice develop a progressive neuronal dysfunction with age-dependent accumulation of mutant CaV2.1 channels

PubMed Central

Watase, Kei; Barrett, Curtis F.; Miyazaki, Taisuke; Ishiguro, Taro; Ishikawa, Kinya; Hu, Yuanxin; Unno, Toshinori; Sun, Yaling; Kasai, Sayumi; Watanabe, Masahiko; Gomez, Christopher M.; Mizusawa, Hidehiro; Tsien, Richard W.; Zoghbi, Huda Y.

2008-01-01

Spinocerebellar ataxia type 6 (SCA6) is a neurodegenerative disorder caused by CAG repeat expansions within the voltage-gated calcium (CaV) 2.1 channel gene. It remains controversial whether the mutation exerts neurotoxicity by changing the function of CaV2.1 channel or through a gain-of-function mechanism associated with accumulation of the expanded polyglutamine protein. We generated three strains of knockin (KI) mice carrying normal, expanded, or hyperexpanded CAG repeat tracts in the Cacna1a locus. The mice expressing hyperexpanded polyglutamine (Sca684Q) developed progressive motor impairment and aggregation of mutant CaV2.1 channels. Electrophysiological analysis of cerebellar Purkinje cells revealed similar Ca2+ channel current density among the three KI models. Neither voltage sensitivity of activation nor inactivation was altered in the Sca684Q neurons, suggesting that expanded CAG repeat per se does not affect the intrinsic electrophysiological properties of the channels. The pathogenesis of SCA6 is apparently linked to an age-dependent process accompanied by accumulation of mutant CaV2.1 channels. PMID:18687887

Numerical study of aero-excitation of steam-turbine rotor blade self-oscillations

NASA Astrophysics Data System (ADS)

Galaev, S. A.; Makhnov, V. Yu.; Ris, V. V.; Smirnov, E. M.

2018-05-01

Blade aero-excitation increment is evaluated by numerical solution of the full 3D unsteady Reynolds-averaged Navier-Stokes equations governing wet steam flow in a powerful steam-turbine last stage. The equilibrium wet steam model was adopted. Blade surfaces oscillations are defined by eigen-modes of a row of blades bounded by a shroud. Grid dependency study was performed with a reduced model being a set of blades multiple an eigen-mode nodal diameter. All other computations were carried out for the entire blade row. Two cases are considered, with an original-blade row and with a row of modified (reinforced) blades. Influence of eigen-mode nodal diameter and blade reinforcing on aero-excitation increment is analyzed. It has been established, in particular, that maximum value of the aero-excitation increment for the reinforced-blade row is two times less as compared with the original-blade row. Generally, results of the study point definitely to less probability of occurrence of blade self-oscillations in case of the reinforced blade-row.

Alternative splicing in the C-terminal tail of Cav2.1 is essential for preventing a neurological disease in mice.

PubMed

Aikawa, Tomonori; Watanabe, Takaki; Miyazaki, Taisuke; Mikuni, Takayasu; Wakamori, Minoru; Sakurai, Miyano; Aizawa, Hidenori; Ishizu, Nobutaka; Watanabe, Masahiko; Kano, Masanobu; Mizusawa, Hidehiro; Watase, Kei

2017-08-15

Alternative splicing (AS) that occurs at the final coding exon (exon 47) of the Cav2.1 voltage-gated calcium channel (VGCC) gene produces two major isoforms in the brain, MPI and MPc. These isoforms differ in their splice acceptor sites; human MPI is translated into a polyglutamine tract associated with spinocerebellar ataxia type 6 (SCA6), whereas MPc splices to an immediate stop codon, resulting in a shorter cytoplasmic tail. To gain insight into the functional role of the AS in vivo and whether modulating the splice patterns at this locus can be a potential therapeutic strategy for SCA6, here we created knockin mice that exclusively express MPc by inserting the splice-site mutation. The resultant Cacna1aCtmKO/CtmKO mice developed non-progressive neurological phenotypes, featuring early-onset ataxia and absence seizure without significant alterations in the basic properties of the channel. Interactions of Cav2.1 with Cavβ4 and Rimbp2 were significantly reduced while those with GABAB2 were enhanced in the cerebellum of Cacna1aCtmKO/CtmKO mice. Treatment with the GABAB antagonist CGP35348 partially rescued the motor impairments seen in Cacna1aCtmKO/CtmKO mice. These results suggest that the carboxyl-terminal domain of Cav2.1 is not essential for maintaining the basic properties of the channel in the cerebellar Purkinje neurons but is involved in multiple interactions of Cav2.1 with other proteins, and plays an essential role in preventing a complex neurological disease. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Massive formation of square array junctions dramatically alters cell shape but does not cause lens opacity in the cav1-KO mice.

PubMed

Biswas, Sondip K; Brako, Lawrence; Lo, Woo-Kuen

2014-08-01

The wavy square array junctions are composed of truncated aquaporin-0 (AQP0) proteins typically distributed in the deep cortical and nuclear fibers in wild-type lenses. These junctions may help maintain the narrowed extracellular spaces between fiber cells to minimize light scattering. Herein, we investigate the impact of the cell shape changes, due to abnormal formation of extensive square array junctions, on the lens opacification in the caveolin-1 knockout mice. The cav1-KO and wild-type mice at age 1-22 months were used. By light microscopy examinations, cav1-KO lenses at age 1-18 months were transparent in both cortical and nuclear regions, whereas some lenses older than 18 months old exhibited nuclear cataracts. Scanning EM consistently observed the massive formation of ridge-and-valley membrane surfaces in young fibers at approximately 150 μm deep in all cav1-KO lenses studied. In contrast, the typical ridge-and-valleys were only seen in mature fibers deeper than 400 μm in wild-type lenses. The resulting extensive ridge-and-valleys dramatically altered the overall cell shape in cav1-KO lenses. Remarkably, despite dramatic shape changes, these deformed fiber cells remained intact and made close contact with their neighboring cells. By freeze-fracture TEM, ridge-and-valleys exhibited the typical orthogonal arrangement of 6.6 nm square array intramembrane particles and displayed the narrowed extracellular spaces. Immunofluorescence analysis showed that AQP0 C-terminus labeling was significantly decreased in outer cortical fibers in cav1-KO lenses. However, freeze-fracture immunogold labeling showed that the AQP0 C-terminus antibody was sparsely distributed on the wavy square array junctions, suggesting that the cleavage of AQP0 C-termini might not yet be complete. The cav1-KO lenses with nuclear cataracts showed complete cellular breakdown and large globule formation in the lens nucleus. This study suggests that despite dramatic cell shape changes, the

PREFACE: 2013 International Conferences on Geological, Geographical, Aerospace and Earth Sciences (AeroEarth 2013)

NASA Astrophysics Data System (ADS)

2014-03-01

The 2013 International Conferences on Geological, Geographical, Aerospace and Earth Sciences (AeroEarth 2013), was held at the Swiss Bell Mangga Besar, Jakarta, Indonesia, on 23 December 2013. The AeroEarth conference aims to bring together researchers, engineers and scientists in the domain of interest from around the world. AeroEarth 2013 promotes interaction between the theoretical, experimental, and applied communities, so that high-level exchange is achieved in new and emerging areas within Earth Science. Through research and development, earth scientists have the power to preserve the planet's different resource domains by providing expert opinion and information about the forces which make life possible on Earth. We would like to express our sincere gratitude to all in the Technical Program Committee who have reviewed the papers and developed a very interesting Conference Program as well as the invited and plenary speakers. This year, we received 91 papers and after rigorous review, 17 papers were accepted. The participants come from 8 countries. There are 3 (three) Plenary Sessions and two invited Speakers. It is an honour to present this volume of IOP Conference Series: Earth and Environmental Science (EES) and we deeply thank the authors for their enthusiastic and high-grade contribution. Finally, we would like to thank the conference chairmen, the members of the steering committee, the organizing committee, the organizing secretariat and the financial support from the conference sponsors that allowed the success of AeroEarth 2013. The AeroEarth 2013 Proceedings Editors Dr. Ford Lumban Gaol Dr. Benfano Soewito Dr. Amit Desai Further information on the invited plenary speakers and photographs from the conference can be found in the pdf.

Effect of fluoride exposure on mRNA expression of cav1.2 and calcium signal pathway apoptosis regulators in PC12 cells.

PubMed

Liao, Qiuxia; Zhang, Rui; Wang, Xiaoyu; Nian, Weiwei; Ke, Lulu; Ouyang, Wei; Zhang, Zigui

2017-09-01

This study investigated the effects of fluoride exposure on the mRNA expression of Cav1.2 calcium signaling pathway and apoptosis regulatory molecules in PC12 cells. The viability of PC12 cell receiving high fluoride (5.0mM) and low fluoride (0.5mM) alone or fluoride combined with L-type calcium channel (LTCC) agonist/inhibitor (5umol/L FPL6417/2umol/L nifedipine) was detected using cell counting kit-8 at different time points (2, 4, 6, 8, 12, 10, and 24h). Changes in the cell configuration were observed after exposing the cells to fluoride for 24h. The expression levels of molecules related to the LTCC were examined, particularly, Cav1.2, c-fos, CAMK II, Bax, and Bcl-2. Fluoride poisoning induced severe cell injuries, such as decreased PC12 cell activity, enhanced cell apoptosis, high c-fos, CAMKII, and Bax mRNA expression levels. Bcl-2 expression level was also reduced. Meanwhile, high fluoride, high fluoride with FPL64176, and low fluoride with FPL64176 enhanced the Cav1.2 expression level. In contrast, low fluoride, high fluoride with nifedipine, and low fluoride with nifedipine reduced the Cav1.2 expression level. Thus, Cav1.2 may be an important molecular target for the fluorosis treatment, and the LTCC inhibitor nifedipine may be an effective drug for fluorosis. Copyright © 2017 Elsevier B.V. All rights reserved.

An integrated aerodynamic/propulsion study for generic aero-space planes based on waverider concepts

NASA Technical Reports Server (NTRS)

Rasmussen, M. L.; Emanuel, George

1989-01-01

The design of a unified aero-space plane based on waverider technology is analyzed. The overall aerodynamic design and performance of an aero-space plane are discussed in terms of the forebody, scramjet, and afterbody. Other subjects considered in the study are combustion/nozzle optimization, the idealized tip-to-tail waverider model, and the two-dimensional minimum length nozzle. Charts and graphs are provided to show the results of the preliminary investigations.

Modeling the Energy Use of a Connected and Automated Transportation System (Poster)

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

Gonder, J.; Brown, A.

Early research points to large potential impacts of connected and automated vehicles (CAVs) on transportation energy use - dramatic savings, increased use, or anything in between. Due to a lack of suitable data and integrated modeling tools to explore these complex future systems, analyses to date have relied on simple combinations of isolated effects. This poster proposes a framework for modeling the potential energy implications from increasing penetration of CAV technologies and for assessing technology and policy options to steer them toward favorable energy outcomes. Current CAV modeling challenges include estimating behavior change, understanding potential vehicle-to-vehicle interactions, and assessing trafficmore » flow and vehicle use under different automation scenarios. To bridge these gaps and develop a picture of potential future automated systems, NREL is integrating existing modeling capabilities with additional tools and data inputs to create a more fully integrated CAV assessment toolkit.« less

Cav1.3 channels control D2-autoreceptor responses via NCS-1 in substantia nigra dopamine neurons

PubMed Central

Dragicevic, Elena; Poetschke, Christina; Duda, Johanna; Schlaudraff, Falk; Lammel, Stephan; Schiemann, Julia; Fauler, Michael; Hetzel, Andrea; Watanabe, Masahiko; Lujan, Rafael; Malenka, Robert C.; Striessnig, Joerg

2014-01-01

Dopamine midbrain neurons within the substantia nigra are particularly prone to degeneration in Parkinson’s disease. Their selective loss causes the major motor symptoms of Parkinson’s disease, but the causes for the high vulnerability of SN DA neurons, compared to neighbouring, more resistant ventral tegmental area dopamine neurons, are still unclear. Consequently, there is still no cure available for Parkinson’s disease. Current therapies compensate the progressive loss of dopamine by administering its precursor l-DOPA and/or dopamine D2-receptor agonists. D2-autoreceptors and Cav1.3-containing L-type Ca2+ channels both contribute to Parkinson’s disease pathology. L-type Ca2+ channel blockers protect SN DA neurons from degeneration in Parkinson’s disease and its mouse models, and they are in clinical trials for neuroprotective Parkinson’s disease therapy. However, their physiological functions in SN DA neurons remain unclear. D2-autoreceptors tune firing rates and dopamine release of SN DA neurons in a negative feedback loop through activation of G-protein coupled potassium channels (GIRK2, or KCNJ6). Mature SN DA neurons display prominent, non-desensitizing somatodendritic D2-autoreceptor responses that show pronounced desensitization in PARK-gene Parkinson’s disease mouse models. We analysed surviving human SN DA neurons from patients with Parkinson’s disease and from controls, and detected elevated messenger RNA levels of D2-autoreceptors and GIRK2 in Parkinson’s disease. By electrophysiological analysis of postnatal juvenile and adult mouse SN DA neurons in in vitro brain-slices, we observed that D2-autoreceptor desensitization is reduced with postnatal maturation. Furthermore, a transient high-dopamine state in vivo, caused by one injection of either l-DOPA or cocaine, induced adult-like, non-desensitizing D2-autoreceptor responses, selectively in juvenile SN DA neurons, but not ventral tegmental area dopamine neurons. With pharmacological

Cav1.3 channels control D2-autoreceptor responses via NCS-1 in substantia nigra dopamine neurons.

PubMed

Dragicevic, Elena; Poetschke, Christina; Duda, Johanna; Schlaudraff, Falk; Lammel, Stephan; Schiemann, Julia; Fauler, Michael; Hetzel, Andrea; Watanabe, Masahiko; Lujan, Rafael; Malenka, Robert C; Striessnig, Joerg; Liss, Birgit

2014-08-01

Dopamine midbrain neurons within the substantia nigra are particularly prone to degeneration in Parkinson's disease. Their selective loss causes the major motor symptoms of Parkinson's disease, but the causes for the high vulnerability of SN DA neurons, compared to neighbouring, more resistant ventral tegmental area dopamine neurons, are still unclear. Consequently, there is still no cure available for Parkinson's disease. Current therapies compensate the progressive loss of dopamine by administering its precursor l-DOPA and/or dopamine D2-receptor agonists. D2-autoreceptors and Cav1.3-containing L-type Ca(2+) channels both contribute to Parkinson's disease pathology. L-type Ca(2+) channel blockers protect SN DA neurons from degeneration in Parkinson's disease and its mouse models, and they are in clinical trials for neuroprotective Parkinson's disease therapy. However, their physiological functions in SN DA neurons remain unclear. D2-autoreceptors tune firing rates and dopamine release of SN DA neurons in a negative feedback loop through activation of G-protein coupled potassium channels (GIRK2, or KCNJ6). Mature SN DA neurons display prominent, non-desensitizing somatodendritic D2-autoreceptor responses that show pronounced desensitization in PARK-gene Parkinson's disease mouse models. We analysed surviving human SN DA neurons from patients with Parkinson's disease and from controls, and detected elevated messenger RNA levels of D2-autoreceptors and GIRK2 in Parkinson's disease. By electrophysiological analysis of postnatal juvenile and adult mouse SN DA neurons in in vitro brain-slices, we observed that D2-autoreceptor desensitization is reduced with postnatal maturation. Furthermore, a transient high-dopamine state in vivo, caused by one injection of either l-DOPA or cocaine, induced adult-like, non-desensitizing D2-autoreceptor responses, selectively in juvenile SN DA neurons, but not ventral tegmental area dopamine neurons. With pharmacological and genetic

Results of investigations conducted in the LaRC 8-foot transonic pressure tunnel using the 0.010-scale 72-OTS model of the space shuttle integrated vehicle (IA93), volume 2

NASA Technical Reports Server (NTRS)

Nichols, M. E.

1976-01-01

Test procedures, history, and plotted coefficient data are presented for an aero-loads investigation on the updated configuration-5 space shuttle launch vehicle at Mach numbers from 0.600 to 1.205. Six-component vehicle forces and moments, base and sting-cavity pressures, elevon hinge moments, wing-root bending and torsion moments, and normal shear force data were obtained. Full simulation of updated vehicle protuberances and attach hardware was employed.

Expression of the P/Q (Cav2.1) calcium channel in nodose sensory neurons and arterial baroreceptors.

PubMed

Tatalovic, Milos; Glazebrook, Patricia A; Kunze, Diana L

2012-06-27

The predominant calcium current in nodose sensory neurons, including the subpopulation of baroreceptor neurons, is the N-type channel, Cav2.2. It is also the primary calcium channel responsible for transmitter release at their presynaptic terminals in the nucleus of the solitary tract in the brainstem. The P/Q channel, Cav2.1, the other major calcium channel responsible for transmitter release at mammalian synapses, represents only 15-20% of total calcium current in the general population of sensory neurons and makes a minor contribution to transmitter release at the presynaptic terminal. In the present study we identified a subpopulation of the largest nodose neurons (capacitance>50pF) in which, surprisingly, Cav2.1 represents over 50% of the total calcium current, differing from the remainder of the population. Consistent with these electrophysiological data, anti-Cav2.1 antibody labeling was more membrane delimited in a subgroup of the large neurons in slices of nodose ganglia. Data reported in other synapses in the central nervous system assign different roles in synaptic information transfer to the P/Q-type versus N-type calcium channels. The study raises the possibility that the P/Q channel which has been associated with high fidelity transmission at other central synapses serves a similar function in this group of large myelinated sensory afferents, including arterial baroreceptors where a high frequency regular discharge pattern signals the pressure pulse. This contrasts to the irregular lower frequency discharge of the unmyelinated fibers that make up the majority of the sensory population and that utilize the N-type channel in synaptic transmission. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Regulation of L-type CaV1.3 channel activity and insulin secretion by the cGMP-PKG signaling pathway

PubMed Central

Sandoval, Alejandro; Duran, Paz; Gandini, María A.; Andrade, Arturo; Almanza, Angélica; Kaja, Simon; Felix, Ricardo

2018-01-01

cGMP is a second messenger widely used in the nervous system and other tissues. One of the major effectors for cGMP is the serine/threonine protein kinase, cGMP-dependent protein kinase (PKG), which catalyzes the phosphorylation of a variety of proteins including ion channels. Previously, it has been shown that the cGMP-PKG signaling pathway inhibits Ca2+ currents in rat vestibular hair cells and chromaffin cells. This current allegedly flow through voltage-gated CaV1.3L-type Ca2+ channels, and is important for controlling vestibular hair cell sensory function and catecholamine secretion, respectively. Here, we show that native L-type channels in the insulin-secreting RIN-m5F cell line, and recombinant CaV1.3 channels heterologously expressed in HEK-293 cells, are regulatory targets of the cGMP-PKG signaling cascade. Our results indicate that the CaVα1 ion-conducting subunit of the CaV1.3 channels is highly expressed in RIN-m5F cells and that the application of 8-Br-cGMP, a membrane-permeable analogue of cGMP, significantly inhibits Ca2+ macroscopic currents and impair insulin release stimulated with high K+. In addition, KT-5823, a specific inhibitor of PKG, prevents the current inhibition generated by 8-Br-cGMP in the heterologous expression system. Interestingly, mutating the putative phosphorylation sites to residues resistant to phosphorylation showed that the relevant PKG sites for CaV1.3 L-type channel regulation centers on two amino acid residues, Ser793 and Ser860, located in the intracellular loop connecting the II and III repeats of the CaVα1 pore-forming subunit of the channel. These findings unveil a novel mechanism for how the cGMP-PKG signaling pathway may regulate CaV1.3 channels and contribute to regulate insulin secretion. PMID:28807144

Host Model Uncertainty in Aerosol Radiative Forcing Estimates - The AeroCom Prescribed Experiment

NASA Astrophysics Data System (ADS)

Stier, P.; Kinne, S.; Bellouin, N.; Myhre, G.; Takemura, T.; Yu, H.; Randles, C.; Chung, C. E.

2012-04-01

Anthropogenic and natural aerosol radiative effects are recognized to affect global and regional climate. However, even for the case of identical aerosol emissions, the simulated direct aerosol radiative forcings show significant diversity among the AeroCom models (Schulz et al., 2006). Our analysis of aerosol absorption in the AeroCom models indicates a larger diversity in the translation from given aerosol radiative properties (absorption optical depth) to actual atmospheric absorption than in the translation of a given atmospheric burden of black carbon to the radiative properties (absorption optical depth). The large diversity is caused by differences in the simulated cloud fields, radiative transfer, the relative vertical distribution of aerosols and clouds, and the effective surface albedo. This indicates that differences in host model (GCM or CTM hosting the aerosol module) parameterizations contribute significantly to the simulated diversity of aerosol radiative forcing. The magnitude of these host model effects in global aerosol model and satellites retrieved aerosol radiative forcing estimates cannot be estimated from the diagnostics of the "standard" AeroCom forcing experiments. To quantify the contribution of differences in the host models to the simulated aerosol radiative forcing and absorption we conduct the AeroCom Prescribed experiment, a simple aerosol model and satellite retrieval intercomparison with prescribed highly idealised aerosol fields. Quality checks, such as diagnostic output of the 3D aerosol fields as implemented in each model, ensure the comparability of the aerosol implementation in the participating models. The simulated forcing variability among the models and retrievals is a direct measure of the contribution of host model assumptions to the uncertainty in the assessment of the aerosol radiative effects. We will present the results from the AeroCom prescribed experiment with focus on the attribution to the simulated variability

Aero-thermo-dynamic analysis of the Spaceliner-7.1 vehicle in high altitude flight

NASA Astrophysics Data System (ADS)

Zuppardi, Gennaro; Morsa, Luigi; Sippel, Martin; Schwanekamp, Tobias

2014-12-01

SpaceLiner, designed by DLR, is a visionary, extremely fast passenger transportation concept. It consists of two stages: a winged booster, a vehicle. After separation of the two stages, the booster makes a controlled re-entry and returns to the launch site. According to the current project, version 7-1 of SpaceLiner (SpaceLiner-7.1), the vehicle should be brought at an altitude of 75 km and then released, undertaking the descent path. In the perspective that the vehicle of SpaceLiner-7.1 could be brought to altitudes higher than 75 km, e.g. 100 km or above and also for a speculative purpose, in this paper the aerodynamic parameters of the SpaceLiner-7.1 vehicle are calculated in the whole transition regime, from continuum low density to free molecular flows. Computer simulations have been carried out by three codes: two DSMC codes, DS3V in the altitude interval 100-250 km for the evaluation of the global aerodynamic coefficients and DS2V at the altitude of 60 km for the evaluation of the heat flux and pressure distributions along the vehicle nose, and the DLR HOTSOSE code for the evaluation of the global aerodynamic coefficients in continuum, hypersonic flow at the altitude of 44.6 km. The effectiveness of the flaps with deflection angle of -35 deg. was evaluated in the above mentioned altitude interval. The vehicle showed longitudinal stability in the whole altitude interval even with no flap. The global bridging formulae verified to be proper for the evaluation of the aerodynamic coefficients in the altitude interval 80-100 km where the computations cannot be fulfilled either by CFD, because of the failure of the classical equations computing the transport coefficients, or by DSMC because of the requirement of very high computer resources both in terms of the core storage (a high number of simulated molecules is needed) and to the very long processing time.

75 FR 904 - Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Model PIAGGIO P-180 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-07

.... PIAGGIO AERO PIAGGIO P.180 Cover No. D2 Revised June 16, 2008. AVANTI Maintenance Manual, Report No. 9066..., Revision No. D2, revised June 16, 2008; or (for S/N 1105 and greater) pages 1 through 8, dated June 30... Dated. Service Bulletin (Mandatory) N. 80-0249. PIAGGIO AERO PIAGGIO P. 180 Cover No. D2 Revised June 16...

Myogenic tone is impaired at low arterial pressure in mice deficient in the low-voltage-activated CaV 3.1 T-type Ca(2+) channel.

PubMed

Björling, K; Morita, H; Olsen, M F; Prodan, A; Hansen, P B; Lory, P; Holstein-Rathlou, N-H; Jensen, L J

2013-04-01

Using mice deficient in the CaV 3.1 T-type Ca(2+) channel, the aim of the present study was to elucidate the molecular identity of non-L-type channels involved in vascular tone regulation in mesenteric arteries and arterioles. We used immunofluorescence microscopy to localize CaV 3.1 channels, patch clamp electrophysiology to test the effects of a putative T-type channel blocker NNC 55-0396 on whole-cell Ca(2+) currents, pressure myography and Ca(2+) imaging to test diameter and Ca(2+) responses of the applied vasoconstrictors, and Q-PCR to check mRNA expression levels of several Ca(2+) handling proteins in wild-type and CaV 3.1(-/-) mice. Our data indicated that CaV 3.1 channels are important for the maintenance of myogenic tone at low pressures (40-80 mm Hg), whereas they are not involved in high-voltage-activated Ca(2+) currents, Ca(2+) entry or vasoconstriction to high KCl in mesenteric arteries and arterioles. Furthermore, we show that NNC 55-0396 is not a specific T-type channel inhibitor, as it potently blocks L-type and non-L-type high-voltage-activated Ca(2+) currents in mouse mesenteric vascular smooth muscle cell. Our data using mice deficient in the CaV 3.1 T-type channel represent new evidence for the involvement of non-L-type channels in arteriolar tone regulation. We showed that CaV 3.1 channels are important for the myogenic tone at low arterial pressure, which is potentially relevant under resting conditions in vivo. Moreover, CaV 3.1 channels are not involved in Ca(2+) entry and vasoconstriction to large depolarization with, for example, high KCl. Finally, we caution against using NNC 55-0396 as a specific T-type channel blocker in native cells expressing high-voltage-activated Ca(2+) channels. Acta Physiologica © 2013 Scandinavian Physiological Society.

Bi-phasic regulation of glycogen content in astrocytes via Cav-1/PTEN/PI3K/AKT/GSK-3β pathway by fluoxetine.

PubMed

Bai, Qiufang; Song, Dan; Gu, Li; Verkhratsky, Alexei; Peng, Liang

2017-04-01

Here, we present the data indicating that chronic treatment with fluoxetine regulates Cav-1/PTEN/PI3K/AKT/GSK-3β signalling pathway and glycogen content in primary cultures of astrocytes with bi-phasic concentration dependence. At lower concentrations, fluoxetine downregulates gene expression of Cav-1, decreases membrane content of PTEN, increases activity of PI3K/AKT, and elevates GSK-3β phosphorylation thus suppressing its activity. At higher concentrations, fluoxetine acts in an inverse fashion. As expected, fluoxetine at lower concentrations increased while at higher concentrations decreased glycogen content in astrocytes. Our findings indicate that bi-phasic regulation of glycogen content via Cav-1/PTEN/PI3K/AKT/GSK-3β pathway by fluoxetine may be responsible for both therapeutic and side effects of the drug.

ω-Conotoxin GVIA Mimetics that Bind and Inhibit Neuronal Cav2.2 Ion Channels

PubMed Central

Tranberg, Charlotte Elisabet; Yang, Aijun; Vette, Irina; McArthur, Jeffrey R.; Baell, Jonathan B.; Lewis, Richard J.; Tuck, Kellie L.; Duggan, Peter J.

2012-01-01

The neuronal voltage-gated N-type calcium channel (Cav2.2) is a validated target for the treatment of neuropathic pain. A small library of anthranilamide-derived ω-Conotoxin GVIA mimetics bearing the diphenylmethylpiperazine moiety were prepared and tested using three experimental measures of calcium channel blockade. These consisted of a 125I-ω-conotoxin GVIA displacement assay, a fluorescence-based calcium response assay with SH-SY5Y neuroblastoma cells, and a whole-cell patch clamp electrophysiology assay with HEK293 cells stably expressing human Cav2.2 channels. A subset of compounds were active in all three assays. This is the first time that compounds designed to be mimics of ω-conotoxin GVIA and found to be active in the 125I-ω-conotoxin GVIA displacement assay have also been shown to block functional ion channels in a dose-dependent manner. PMID:23170089

Heat pipes for wing leading edges of hypersonic vehicles

NASA Technical Reports Server (NTRS)

Boman, B. L.; Citrin, K. M.; Garner, E. C.; Stone, J. E.

1990-01-01

Wing leading edge heat pipes were conceptually designed for three types of vehicle: an entry research vehicle, aero-space plane, and advanced shuttle. A full scale, internally instrumented sodium/Hastelloy X heat pipe was successfully designed and fabricated for the advanced shuttle application. The 69.4 inch long heat pipe reduces peak leading edge temperatures from 3500 F to 1800 F. It is internally instrumented with thermocouples and pressure transducers to measure sodium vapor qualities. Large thermal gradients and consequently large thermal stresses, which have the potential of limiting heat pipe life, were predicted to occur during startup. A test stand and test plan were developed for subsequent testing of this heat pipe. Heat pipe manufacturing technology was advanced during this program, including the development of an innovative technique for wick installation.

Dynamical mechanism in aero-engine gas path system using minimum spanning tree and detrended cross-correlation analysis

NASA Astrophysics Data System (ADS)

Dong, Keqiang; Zhang, Hong; Gao, You

2017-01-01

Identifying the mutual interaction in aero-engine gas path system is a crucial problem that facilitates the understanding of emerging structures in complex system. By employing the multiscale multifractal detrended cross-correlation analysis method to aero-engine gas path system, the cross-correlation characteristics between gas path system parameters are established. Further, we apply multiscale multifractal detrended cross-correlation distance matrix and minimum spanning tree to investigate the mutual interactions of gas path variables. The results can infer that the low-spool rotor speed (N1) and engine pressure ratio (EPR) are main gas path parameters. The application of proposed method contributes to promote our understanding of the internal mechanisms and structures of aero-engine dynamics.

Synthesis Study on Transitions in Signal Infrastructure and Control Algorithms for Connected and Automated Transportation

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

Aziz, H. M. Abdul; Wang, Hong; Young, Stan

Documenting existing state of practice is an initial step in developing future control infrastructure to be co-deployed for heterogeneous mix of connected and automated vehicles with human drivers while leveraging benefits to safety, congestion, and energy. With advances in information technology and extensive deployment of connected and automated vehicle technology anticipated over the coming decades, cities globally are making efforts to plan and prepare for these transitions. CAVs not only offer opportunities to improve transportation systems through enhanced safety and efficient operations of vehicles. There are also significant needs in terms of exploring how best to leverage vehicle-to-vehicle (V2V) technology,more » vehicle-to-infrastructure (V2I) technology and vehicle-to-everything (V2X) technology. Both Connected Vehicle (CV) and Connected and Automated Vehicle (CAV) paradigms feature bi-directional connectivity and share similar applications in terms of signal control algorithm and infrastructure implementation. The discussion in our synthesis study assumes the CAV/CV context where connectivity exists with or without automated vehicles. Our synthesis study explores the current state of signal control algorithms and infrastructure, reports the completed and newly proposed CV/CAV deployment studies regarding signal control schemes, reviews the deployment costs for CAV/AV signal infrastructure, and concludes with a discussion on the opportunities such as detector free signal control schemes and dynamic performance management for intersections, and challenges such as dependency on market adaptation and the need to build a fault-tolerant signal system deployment in a CAV/CV environment. The study will serve as an initial critical assessment of existing signal control infrastructure (devices, control instruments, and firmware) and control schemes (actuated, adaptive, and coordinated-green wave). Also, the report will help to identify the future needs for the

Electrophysiological evidence for voltage-gated calcium channel 2 (Cav2) modulation of mechano- and thermosensitive spinal neuronal responses in a rat model of osteoarthritis.

PubMed

Rahman, W; Patel, R; Dickenson, A H

2015-10-01

Osteoarthritis (OA) remains one of the greatest healthcare burdens in western society, with chronic debilitating pain-dominating clinical presentation yet therapeutic strategies are inadequate in many patients. Development of better analgesics is contingent on improved understanding of the molecular mechanisms mediating OA pain. Voltage-gated calcium channels 2.2 (Cav2.2) play a critical role in spinal nociceptive transmission, therefore blocking Cav2.2 activity represents an attractive opportunity for OA pain treatment, but the only available licensed Cav2.2 antagonist ziconitide (PrilatTM) is of limited use. TROX-1 is an orally available, use dependent and state-selective Cav2 antagonist, exerting its analgesic effect primarily via Cav2.2 blockade, with an improved therapeutic window compared with ziconitide. Using a rat model of monosodium iodoacetate (MIA), 2 mg, induced OA we used in vivo electrophysiology to assess the effects of spinal or systemic administration of TROX-1 on the evoked activity of wide dynamic range spinal dorsal horn neurons in response to electrical, natural mechanical (dynamic brush and von Frey 2, 8, 26 and 6 g) and thermal (40, 45 and 45 °C) stimuli applied to the peripheral receptive field. MIA injection into the knee joint resulted in mechanical hypersensitivity of the ipsilateral hind paw and weight-bearing asymmetry. Spinal administration of TROX-1 (0.1 and 1 μg/50 μl) produced a significant dose-related inhibition of dynamic brush, mechanical (von Frey filament (vF) 8, 26 and 60 g) and noxious thermal-(45 and 48 °C) evoked neuronal responses in MIA rats only. Systemic administration of TROX-1 produced a significant inhibition of the mechanical-(vF 8, 26 and 60 g) evoked neuronal responses in MIA rats. TROX-1 did not produce any significant effect on any neuronal measure in Sham controls. Our in vivo electrophysiological results demonstrate a pathological state-dependent effect of TROX-1, which suggests an increased functional

Electrophysiological evidence for voltage-gated calcium channel 2 (Cav2) modulation of mechano- and thermosensitive spinal neuronal responses in a rat model of osteoarthritis

PubMed Central

Rahman, W.; Patel, R.; Dickenson, A.H.

2015-01-01

Osteoarthritis (OA) remains one of the greatest healthcare burdens in western society, with chronic debilitating pain-dominating clinical presentation yet therapeutic strategies are inadequate in many patients. Development of better analgesics is contingent on improved understanding of the molecular mechanisms mediating OA pain. Voltage-gated calcium channels 2.2 (Cav2.2) play a critical role in spinal nociceptive transmission, therefore blocking Cav2.2 activity represents an attractive opportunity for OA pain treatment, but the only available licensed Cav2.2 antagonist ziconitide (PrilatTM) is of limited use. TROX-1 is an orally available, use dependent and state-selective Cav2 antagonist, exerting its analgesic effect primarily via Cav2.2 blockade, with an improved therapeutic window compared with ziconitide. Using a rat model of monosodium iodoacetate (MIA), 2 mg, induced OA we used in vivo electrophysiology to assess the effects of spinal or systemic administration of TROX-1 on the evoked activity of wide dynamic range spinal dorsal horn neurons in response to electrical, natural mechanical (dynamic brush and von Frey 2, 8, 26 and 6 g) and thermal (40, 45 and 45 °C) stimuli applied to the peripheral receptive field. MIA injection into the knee joint resulted in mechanical hypersensitivity of the ipsilateral hind paw and weight-bearing asymmetry. Spinal administration of TROX-1 (0.1 and 1 μg/50 μl) produced a significant dose-related inhibition of dynamic brush, mechanical (von Frey filament (vF) 8, 26 and 60 g) and noxious thermal-(45 and 48 °C) evoked neuronal responses in MIA rats only. Systemic administration of TROX-1 produced a significant inhibition of the mechanical-(vF 8, 26 and 60 g) evoked neuronal responses in MIA rats. TROX-1 did not produce any significant effect on any neuronal measure in Sham controls. Our in vivo electrophysiological results demonstrate a pathological state-dependent effect of TROX-1, which suggests an increased

Calcium sensor regulation of the CaV2.1 Ca2+ channel contributes to short-term synaptic plasticity in hippocampal neurons.

PubMed

Nanou, Evanthia; Sullivan, Jane M; Scheuer, Todd; Catterall, William A

2016-01-26

Short-term synaptic plasticity is induced by calcium (Ca(2+)) accumulating in presynaptic nerve terminals during repetitive action potentials. Regulation of voltage-gated CaV2.1 Ca(2+) channels by Ca(2+) sensor proteins induces facilitation of Ca(2+) currents and synaptic facilitation in cultured neurons expressing exogenous CaV2.1 channels. However, it is unknown whether this mechanism contributes to facilitation in native synapses. We introduced the IM-AA mutation into the IQ-like motif (IM) of the Ca(2+) sensor binding site. This mutation does not alter voltage dependence or kinetics of CaV2.1 currents, or frequency or amplitude of spontaneous miniature excitatory postsynaptic currents (mEPSCs); however, synaptic facilitation is completely blocked in excitatory glutamatergic synapses in hippocampal autaptic cultures. In acutely prepared hippocampal slices, frequency and amplitude of mEPSCs and amplitudes of evoked EPSCs are unaltered. In contrast, short-term synaptic facilitation in response to paired stimuli is reduced by ∼ 50%. In the presence of EGTA-AM to prevent global increases in free Ca(2+), the IM-AA mutation completely blocks short-term synaptic facilitation, indicating that synaptic facilitation by brief, local increases in Ca(2+) is dependent upon regulation of CaV2.1 channels by Ca(2+) sensor proteins. In response to trains of action potentials, synaptic facilitation is reduced in IM-AA synapses in initial stimuli, consistent with results of paired-pulse experiments; however, synaptic depression is also delayed, resulting in sustained increases in amplitudes of later EPSCs during trains of 10 stimuli at 10-20 Hz. Evidently, regulation of CaV2.1 channels by CaS proteins is required for normal short-term plasticity and normal encoding of information in native hippocampal synapses.

Simultaneous measurement of aero-optical distortion and turbulent structure in a heated boundary layer

NASA Astrophysics Data System (ADS)

Saxton-Fox, Theresa; McKeon, Beverley; Smith, Adam; Gordeyev, Stanislav

2014-11-01

This study examines the relationship between turbulent structures and the aero-optical distortion of a laser beam passing through a turbulent boundary layer. Previous studies by Smith et al. (AIAA, 2014--2491) have found a bulk convection velocity of 0 . 8U∞ for aero-optical distortion in turbulent boundary layers, motivating a comparison of the distortion with the outer boundary layer. In this study, a turbulent boundary layer is developed over a flat plate with a moderately-heated section of length 25 δ . Density variation in the thermal boundary layer leads to aero-optical distortion, which is measured with a Malley probe (Smith et al., AIAA, 2013--3133). Simultaneously, 2D PIV measurements are recorded in a wall-normal, streamwise plane centered on the Malley probe location. Experiments are run at Reθ = 2100 and at a Mach number of 0.03, with the heated wall 10 to 20°C above the free stream temperature. Correlations and conditional averages are carried out between Malley probe distortion angles and flow features in the PIV vector fields. Aero-optical distortion in this study will be compared to distortion in higher Mach number flows studied by Gordeyev et al. (J. Fluid Mech., 2014), with the aim of extending conclusions into compressible flows. This research is made possible by the Department of Defense through the National Defense & Engineering Graduate Fellowship (NDSEG) Program and by the Air Force Office of Scientific Research Grant # FA9550-12-1-0060.

Effect of structurally related flavonoids from Zuccagnia punctata Cav. on Caenorhabditis elegans.

PubMed

D'Almeida, Romina E; Alberto, María R; Morgan, Phillip; Sedensky, Margaret; Isla, María I

2014-03-01

Zuccagnia punctata Cav. (Fabaceae), commonly called jarilla macho or pus-pus, is being used in traditional medicine as an antiseptic, anti-inflammatory and to relieve muscle and bone pain. The aim of this work was to study the anthelmintic effects of three structurally related flavonoids present in aerial parts of Z. punctata Cav. The biological activity of the flavonoids 7-hydroxyflavanone (HF), 3,7-dihydroxyflavone (DHF) and 2´,4´-dihydroxychalcone (DHC) was examined in the free-living nematode Caenorhabditis elegans. Our results showed that among the assayed flavonoids, only DHC showed an anthelmintic effect and alteration of egg hatching and larval development processes in C. elegans. DHC was able to kill 50% of adult nematodes at a concentration of 17 μg/mL. The effect on larval development was observed after 48 h in the presence of 25 and 50 μg/mL DHC, where 33.4 and 73.4% of nematodes remained in the L3 stage or younger. New therapeutic drugs with good efficacy against drug-resistant nematodes are urgently needed. Therefore, DHC, a natural compound present in Z. punctata, is proposed as a potential anthelmintic drug.

Aero-Thermal Calibration of the NASA Glenn Icing Research Tunnel (2004 and 2005 Tests)

NASA Technical Reports Server (NTRS)

Arrington, E. Allen; Pastor, Christine M.; Gonsalez, Jose C.; Curry, Monroe R., III

2010-01-01

A full aero-thermal calibration of the NASA Glenn Icing Research Tunnel was completed in 2004 following the replacement of the inlet guide vanes upstream of the tunnel drive system and improvement to the facility total temperature instrumentation. This calibration test provided data used to fully document the aero-thermal flow quality in the IRT test section and to construct calibration curves for the operation of the IRT. The 2004 test was also the first to use the 2-D RTD array, an improved total temperature calibration measurement platform.

A comparison between different finite elements for elastic and aero-elastic analyses.

PubMed

Mahran, Mohamed; ELsabbagh, Adel; Negm, Hani

2017-11-01

In the present paper, a comparison between five different shell finite elements, including the Linear Triangular Element, Linear Quadrilateral Element, Linear Quadrilateral Element based on deformation modes, 8-node Quadrilateral Element, and 9-Node Quadrilateral Element was presented. The shape functions and the element equations related to each element were presented through a detailed mathematical formulation. Additionally, the Jacobian matrix for the second order derivatives was simplified and used to derive each element's strain-displacement matrix in bending. The elements were compared using carefully selected elastic and aero-elastic bench mark problems, regarding the number of elements needed to reach convergence, the resulting accuracy, and the needed computation time. The best suitable element for elastic free vibration analysis was found to be the Linear Quadrilateral Element with deformation-based shape functions, whereas the most suitable element for stress analysis was the 8-Node Quadrilateral Element, and the most suitable element for aero-elastic analysis was the 9-Node Quadrilateral Element. Although the linear triangular element was the last choice for modal and stress analyses, it establishes more accurate results in aero-elastic analyses, however, with much longer computation time. Additionally, the nine-node quadrilateral element was found to be the best choice for laminated composite plates analysis.

Airborne Aero-Optics Laboratory - Transonic (AAOL-T)

DTIC Science & Technology

2016-10-03

122–151. [30] DeGraaff, D. B. and Eaton, J. K., “Reynolds-Number Scaling of the Flat - Plate Turbulent Boundary Layer ,” Journal of Fluid Mechanics, Vol...elevation angle of the turret is fixed at 120 o . The inflow turbulence data are generated by a separate flat - plate boundary layers simulation. The...aero-optical distortion magnitude for turbulent boundary layers . Subsonic Flow over a Cylindrical Turret with a Flat Window. The flow over a

AeroVironment technician checks a Helios solar cell panel

NASA Technical Reports Server (NTRS)

2000-01-01

A technician at AeroVironment's Design Development Center in Simi Valley, California, checks a panel of silicon solar cells for conductivity and voltage. The bi-facial cells, fabricated by SunPower, Inc., of Sunnyvale, California, are among 64,000 solar cells which have been installed on the Helios Prototype solar-powered aircraft to provide power to its 14 electric motors and operating systems. Developed by AeroVironment under NASA's Environmental Research Aircraft and Sensor Technology (ERAST) project, the Helios Prototype is the forerunner of a planned fleet of slow-flying, long duration, high-altitude aircraft which can perform atmospheric science missions and serve as telecommunications relay platforms in the stratosphere. Target goals set by NASA for the giant 246-foot span flying wing include reaching and sustaining subsonic horizontal flight at 100,000 feet altitude in 2001, and sustained continuous flight for at least four days and nights above 50,000 feet altitude with the aid of a regenerative fuel cell-based energy storage system now under development in 2003.

Development and Validation of a New Blade Element Momentum Skewed-Wake Model within AeroDyn: Preprint

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

Ning, S. A.; Hayman, G.; Damiani, R.

Blade element momentum methods, though conceptually simple, are highly useful for analyzing wind turbines aerodynamics and are widely used in many design and analysis applications. A new version of AeroDyn is being developed to take advantage of new robust solution methodologies, conform to a new modularization framework for National Renewable Energy Laboratory's FAST, utilize advanced skewed-wake analysis methods, fix limitations with previous implementations, and to enable modeling of highly flexible and nonstraight blades. This paper reviews blade element momentum theory and several of the options available for analyzing skewed inflow. AeroDyn implementation details are described for the benefit of usersmore » and developers. These new options are compared to solutions from the previous version of AeroDyn and to experimental data. Finally, recommendations are given on how one might select from the various available solution approaches.« less

Survey of Aerothermodynamics Facilities Useful for the Design of Hypersonic Vehicles Using Air-Breathing Propulsion

NASA Technical Reports Server (NTRS)

Arnold, James O.; Deiwert, G. S.

1997-01-01

The dream of producing an air-breathing, hydrogen fueled, hypervelocity aircraft has been before the aerospace community for decades. However, such a craft has not yet been realized, even in an experimental form. Despite the simplicity and beauty of the concept, many formidable problems must be overcome to make this dream a reality. This paper summarizes the aero/aerothermodynamic issues that must be addressed to make the dream a reality and discusses how aerothermodynamics facilities and their modem companion, real-gas computational fluid dynamics (CFD), can help solve the problems blocking the way to realizing the dream. The approach of the paper is first to outline the concept of an air-breathing hypersonic vehicle and then discuss the nose-to-tail aerothermodynamics issues and special aerodynamic problems that arise with such a craft. Then the utility of aerothermodynamic facilities and companion CFD analysis is illustrated by reviewing results from recent United States publications wherein these problems have been addressed. Papers selected for the discussion have k e n chosen such that the review will serve to survey important U.S. aero/aerothermodynamic real gas and conventional wind tunnel facilities that are useful in the study of hypersonic, hydrogen propelled hypervelocity vehicles.

Voltage-independent inhibition of Ca(V)2.2 channels is delimited to a specific region of the membrane potential in rat SCG neurons.

PubMed

Vivas, Oscar; Arenas, Isabel; García, David E

2012-06-01

Neurotransmitters and hormones regulate Ca(V)2.2 channels through a voltage-independent pathway which is not well understood. It has been suggested that this voltage-independent inhibition is constant at all membrane voltages. However, changes in the percent of voltage-independent inhibition of Ca(V)2.2 have not been tested within a physiological voltage range. Here, we used a double-pulse protocol to isolate the voltage-independent inhibition of Ca(V)2.2 channels induced by noradrenaline in rat superior cervical ganglion neurons. To assess changes in the percent of the voltage-independent inhibition, the activation voltage of the channels was tested between -40 and +40 mV. We found that the percent of voltage-independent inhibition induced by noradrenaline changed with the activation voltage used. In addition, voltage-independent inhibition induced by oxo-M, a muscarinic agonist, exhibited the same dependence on activation voltage, which supports that this pattern is not exclusive for adrenergic activation. Our results suggested that voltage-independent inhibition of Ca(V)2.2 channels depends on the activation voltage of the channel in a physiological voltage range. This may have relevant implications in the understanding of the mechanism involved in voltage-independent inhibition.

Identification of interleukin-1 beta as a key mediator in the upregulation of Cav3.2–USP5 interactions in the pain pathway

PubMed Central

Stemkowski, Patrick L; Garcia-Caballero, Agustin; Gadotti, Vinicius M; M’Dahoma, Said; Chen, Lina; Souza, Ivana A

2017-01-01

We recently reported that nerve injury or peripheral inflammation triggers an upregulation of the deubiquitinase, USP5 in mouse dorsal root ganglion and spinal dorsal horn. This leads to dysregulated ubiquitination of Cav3.2 T-type calcium channels, thus increasing Cav3.2 channel plasma membrane expression and nociceptive signaling in the primary afferent pain pathway. This phenomenon could be recapitulated by noninvasive, optogenetic activation of transient receptor potential vanilloid-1–expressing nociceptors, indicating that neuronal activity is a key player in this process. Given the relevance of the pro-inflammatory cytokine interleukin-1 beta in many forms of pathological pain, we hypothesized that interleukin-1 beta may be a critical cofactor required to drive upregulation of interactions between USP5 and Cav3.2 channels. Here, we report that gene expression, as well as protein levels for interleukin-1 beta and the endogenous interleukin-1 receptor-I antagonist, IL-1Ra are unaltered following conditioning stimulation of optogenetically targeted cutaneous nociceptors, indicating that neuronal activity is not a driver of interleukin-1 beta signaling. In contrast, co-immunoprecipitation experiments revealed that intrathecal administration of interleukin-1 beta in wild-type mice led to an increase in the interaction between USP5 and Cav3.2 in the spinal dorsal horn. Moreover, disruption of the interaction between USP5 and Cav3.2 with TAT peptides suppressed acute nocifensive responses produced by interleukin-1 beta, which was similar to that achieved by elimination of T-type channel activity with the channel blockers, mibefradil, or TTA-A2. Finally, this upregulation could be maintained in dorsal root ganglion neuron cultures exposed overnight to interleukin-1 beta, while the copresence of interleukin-1 receptor antagonist or the dampening of neuronal cell activity with tetrodotoxin attenuated this response. Altogether, our findings identify interleukin-1 beta

Machining the Integral Impeller and Blisk of Aero-Engines: A Review of Surface Finishing and Strengthening Technologies

NASA Astrophysics Data System (ADS)

Fu, Youzhi; Gao, Hang; Wang, Xuanping; Guo, Dongming

2017-05-01

The integral impeller and blisk of an aero-engine are high performance parts with complex structure and made of difficult-to-cut materials. The blade surfaces of the integral impeller and blisk are functional surfaces for power transmission, and their surface integrity has significant effects on the aerodynamic efficiency and service life of an aero-engine. Thus, it is indispensable to finish and strengthen the blades before use. This paper presents a comprehensive literature review of studies on finishing and strengthening technologies for the impeller and blisk of aero-engines. The review includes independent and integrated finishing and strengthening technologies and discusses advanced rotational abrasive flow machining with back-pressure used for finishing the integral impeller and blisk. A brief assessment of future research problems and directions is also presented.

48 CFR 1852.235-70 - Center for AeroSpace Information.

Code of Federal Regulations, 2013 CFR

2013-10-01

... avail itself of the services provided by the NASA Center for AeroSpace Information (CASI) (http://www.sti.nasa.gov) for the conduct of research or research and development required under this contract. CASI provides a variety of services and products as a NASA repository and database of research...

48 CFR 1852.235-70 - Center for AeroSpace Information.

Code of Federal Regulations, 2011 CFR

2011-10-01

... avail itself of the services provided by the NASA Center for AeroSpace Information (CASI) (http://www.sti.nasa.gov) for the conduct of research or research and development required under this contract. CASI provides a variety of services and products as a NASA repository and database of research...

Alternative Fuels Data Center

Science.gov Websites

Transportation Department (ITD) established the Connected and Autonomous Vehicle (CAV) Testing and Deployment testing and deployment of CAVs, coordinate with the identified agencies about how to administer the testing of CAVs on roads, review existing state statues and administrative rules that impede the testing

Spectral Behavior of Weakly Compressible Aero-Optical Distortions

NASA Astrophysics Data System (ADS)

Mathews, Edwin; Wang, Kan; Wang, Meng; Jumper, Eric

2016-11-01

In classical theories of optical distortions by atmospheric turbulence, an appropriate and key assumption is that index-of-refraction variations are dominated by fluctuations in temperature and the effects of turbulent pressure fluctuations are negligible. This assumption is, however, not generally valid for aero-optical distortions caused by turbulent flow over an optical aperture, where both temperature and pressures fluctuations may contribute significantly to the index-of-refraction fluctuations. A general expression for weak fluctuations in refractive index is derived using the ideal gas law and Gladstone-Dale relation and applied to describe the spectral behavior of aero-optical distortions. Large-eddy simulations of weakly compressible, temporally evolving shear layers are then used to verify the theoretical results. Computational results support theoretical findings and confirm that if the log slope of the 1-D density spectrum in the inertial range is -mρ , the optical phase distortion spectral slope is given by - (mρ + 1) . The value of mρ is then shown to be dependent on the ratio of shear-layer free-stream densities and bounded by the spectral slopes of temperature and pressure fluctuations. Supported by HEL-JTO through AFOSR Grant FA9550-13-1-0001 and Blue Waters Graduate Fellowship Program.

C-Band Airport Surface Communications System Standards Development. Phase II Final Report. Volume 2: Test Bed Performance Evaluation and Final AeroMACS Recommendations

NASA Technical Reports Server (NTRS)

Hall, Edward; Magner, James

2011-01-01

This report is provided as part of ITT s NASA Glenn Research Center Aerospace Communication Systems Technical Support (ACSTS) contract NNC05CA85C, Task 7: New ATM Requirements-Future Communications, C-Band and L-Band Communications Standard Development and was based on direction provided by FAA project-level agreements for New ATM Requirements-Future Communications. Task 7 included two subtasks. Subtask 7-1 addressed C-band (5091- to 5150-MHz) airport surface data communications standards development, systems engineering, test bed and prototype development, and tests and demonstrations to establish operational capability for the Aeronautical Mobile Airport Communications System (AeroMACS). Subtask 7-2 focused on systems engineering and development support of the L-band digital aeronautical communications system (L-DACS). Subtask 7-1 consisted of two phases. Phase I included development of AeroMACS concepts of use, requirements, architecture, and initial high-level safety risk assessment. Phase II builds on Phase I results and is presented in two volumes. Volume I is devoted to concepts of use, system requirements, and architecture, including AeroMACS design considerations. Volume II (this document) describes an AeroMACS prototype evaluation and presents final AeroMACS recommendations. This report also describes airport categorization and channelization methodologies. The purposes of the airport categorization task were (1) to facilitate initial AeroMACS architecture designs and enable budgetary projections by creating a set of airport categories based on common airport characteristics and design objectives, and (2) to offer high-level guidance to potential AeroMACS technology and policy development sponsors and service providers. A channelization plan methodology was developed because a common global methodology is needed to assure seamless interoperability among diverse AeroMACS services potentially supplied by multiple service providers.

A History of Army Aviation, 1950-1962. Phase 2: 1955-1962

DTIC Science & Technology

1976-11-01

belief that this probably would be the largest fixed wing aircraft capable of operation in forward areas and that it would be an economical and...opera- tions. CONARC on 18 September pointed out that the aero reconnais- sance concept differed from the SKY CAV concept in tactics and techniques...disclosed numerous inequities . Accordingly, CONARC recommended up- gradings or downgradings of aviator spaces in twenty of the TOE’s. 18 For a

Comparison of caffeine disposition following administration by oral solution (energy drink) and inspired powder (AeroShot) in human subjects.

PubMed

Laizure, S Casey; Meibohm, Bernd; Nelson, Kembral; Chen, Feng; Hu, Zhe-Yi; Parker, Robert B

2017-12-01

To determine the disposition and effects of caffeine after administration using a new dosage form (AeroShot) that delivers caffeine by inspiration of a fine powder into the oral cavity and compare it to an equivalent dose of an oral solution (energy drink) as the reference standard. Healthy human subjects (n = 17) inspired a 100 mg caffeine dose using the AeroShot device or consumed an energy drink on separate study days. Heart rate, blood pressure and subject assessments of effects were measured over an 8-h period. Plasma concentrations of caffeine and its major metabolites were determined by liquid chromatography-mass spectrometry. Pharmacokinetic, cardiovascular and perceived stimulant effects were compared between AeroShot and energy drink phases using a paired t test and standard bioequivalency analysis. Caffeine disposition was similar after caffeine administration by the AeroShot device and energy drink: peak plasma concentration 1790 and 1939 ng ml -1 , and area under the concentration-time curve (AUC) 15 579 and 17 569 ng ml -1 × h, respectively, but they were not bioequivalent: AeroShot AUC of 80.3% (confidence interval 71.2-104.7%) and peak plasma concentration of 86.3% (confidence interval 62.8-102.8%) compared to the energy drink. Female subjects did have a significantly larger AUC compared to males after consumption of the energy drink. The heart rate and blood pressure were not significantly affected by the 100 mg caffeine dose, and there were no consistently perceived stimulant effects by the subjects using visual analogue scales. Inspiration of caffeine as a fine powder using the AeroShot device produces a similar caffeine profile and effects compared to administration of an oral solution (energy drink). © 2017 The British Pharmacological Society.

General aviation accidents : the United States Air Force Aero Club solution

DOT National Transportation Integrated Search

1998-08-01

Aviation if an intrisically safe mode of travel. In 1994, the United States Air Force system of Aero Clubs put forth substantial effort to put a program in place (Fly Smart) to improve flying safety in it aircraft. This study compares the accident ra...

Hydrogen sulfide-induced itch requires activation of Cav3.2 T-type calcium channel in mice

PubMed Central

Wang, Xue-Long; Tian, Bin; Huang, Ya; Peng, Xiao-Yan; Chen, Li-Hua; Li, Jun-Cheng; Liu, Tong

2015-01-01

The contributions of gasotransmitters to itch sensation are largely unknown. In this study, we aimed to investigate the roles of hydrogen sulfide (H2S), a ubiquitous gasotransmitter, in itch signaling. We found that intradermal injection of H2S donors NaHS or Na2S, but not GYY4137 (a slow-releasing H2S donor), dose-dependently induced scratching behavior in a μ-opioid receptor-dependent and histamine-independent manner in mice. Interestingly, NaHS induced itch via unique mechanisms that involved capsaicin-insensitive A-fibers, but not TRPV1-expressing C-fibers that are traditionally considered for mediating itch, revealed by depletion of TRPV1-expressing C-fibers by systemic resiniferatoxin treatment. Moreover, local application of capsaizapine (TRPV1 blocker) or HC-030031 (TRPA1 blocker) had no effects on NaHS-evoked scratching. Strikingly, pharmacological blockade and silencing of Cav3.2 T-type calcium channel by mibefradil, ascorbic acid, zinc chloride or Cav3.2 siRNA dramatically decreased NaHS-evoked scratching. NaHS induced robust alloknesis (touch-evoked itch), which was inhibited by T-type calcium channels blocker mibefradil. Compound 48/80-induced itch was enhanced by an endogenous precursor of H2S (L-cysteine) but attenuated by inhibitors of H2S-producing enzymes cystathionine γ-lyase and cystathionine β-synthase. These results indicated that H2S, as a novel nonhistaminergic itch mediator, may activates Cav3.2 T-type calcium channel, probably located at A-fibers, to induce scratching and alloknesis in mice. PMID:26602811

Future orbital transfer vehicle technology study. Volume 2: Technical report

NASA Technical Reports Server (NTRS)

Davis, E. E.

1982-01-01

Missions for future orbit transfer vehicles (1995-2010) are identified and the technology, operations and vehicle concepts that satisfy the transportation requirements are defined. Comparison of reusable space and ground based LO2/LH2 OTV's was made. Both vehicles used advanced space engines and aero assist capability. The SB OTV provided advantages in life cycle cost, performance and potential for improvement. Comparison of an all LO2/LH2 OTV fleet with a fleet of LO2/LH2 OTVs and electric OTV's was also made. The normal growth technology electric OTV used silicon cells with heavy shielding and argon ion thrusters. This provided a 23% advantage in total transportation cost. The impact of accelerated technology was considered in terms of improvements in performance and cost effectiveness. The accelerated technology electric vehicle used GaAs cells and annealing but did not result in the mixed fleet being any cheaper than an all LO2/LH2 OTV fleet. It is concluded that reusable LO2/LH2 OTV's can serve all general purpose cargo roles between LEO and GEO for the forseeable future. The most significant technology for the second generation vehicle would be space debris protection, on-orbit propellant storage and transfer and on-orbit maintenance capability.

Overview of NASA Power Technologies for Space and Aero Applications

NASA Technical Reports Server (NTRS)

Beach, Raymond F.

2014-01-01

To achieve the ambitious goals that NASA has outlined for the next decades considerable development of power technology will be necessary. This presentation outlines the development objectives for both the space and aero applications. It further looks at the various power technologies that support these objectives and examines drivers that will be a driving force for future development.

Control Relevant Modeling and Design of Scramjet-Powered Hypersonic Vehicles

NASA Astrophysics Data System (ADS)

Dickeson, Jeffrey James

This report provides an overview of scramjet-powered hypersonic vehicle modeling and control challenges. Such vehicles are characterized by unstable non-minimum phase dynamics with significant coupling and low thrust margins. Recent trends in hypersonic vehicle research are summarized. To illustrate control relevant design issues and tradeoffs, a generic nonlinear 3DOF longitudinal dynamics model capturing aero-elastic-propulsive interactions for wedge-shaped vehicle is used. Limitations of the model are discussed and numerous modifications have been made to address control relevant needs. Two different baseline configurations are examined over a two-stage to orbit ascent trajectory. The report highlights how vehicle level-flight static (trim) and dynamic properties change over the trajectory. Thermal choking constraints are imposed on control system design as a direct consequence of having a finite FER margin. The implication of this state-dependent nonlinear FER margin constraint, the right half plane (RHP) zero, and lightly damped flexible modes, on control system bandwidth (BW) and FPA tracking has been discussed. A control methodology has been proposed that addresses the above dynamics while providing some robustness to modeling uncertainty. Vehicle closure (the ability to fly a trajectory segment subject to constraints) is provided through a proposed vehicle design methodology. The design method attempts to use open loop metrics whenever possible to design the vehicle. The design method is applied to a vehicle/control law closed loop nonlinear simulation for validation. The 3DOF longitudinal modeling results are validated against a newly released NASA 6DOF code.

Radiative forcing of the direct aerosol effect from AeroCom Phase II simulations

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

Myhre, G.; Samset, B. H.; Schulz, M.

2013-01-01

We report on the AeroCom Phase II direct aerosol effect (DAE) experiment where 16 detailed global aerosol models have been used to simulate the changes in the aerosol distribution over the industrial era. All 16 models have estimated the radiative forcing (RF) of the anthropogenic DAE, and have taken into account anthropogenic sulphate, black carbon (BC) and organic aerosols (OA) from fossil fuel, biofuel, and biomass burning emissions. In addition several models have simulated the DAE of anthropogenic nitrate and anthropogenic influenced secondary organic aerosols (SOA). The model simulated all-sky RF of the DAE from total anthropogenic aerosols has amore » range from -0.58 to -0.02 Wm -2, with a mean of -0.27 Wm -2 for the 16 models. Several models did not include nitrate or SOA and modifying the estimate by accounting for this with information from the other AeroCom models reduces the range and slightly strengthens the mean. Modifying the model estimates for missing aerosol components and for the time period 1750 to 2010 results in a mean RF for the DAE of -0.35 Wm -2. Compared to AeroCom Phase I (Schulz et al., 2006) we find very similar spreads in both total DAE and aerosol component RF. However, the RF of the total DAE is stronger negative and RF from BC from fossil fuel and biofuel emissions are stronger positive in the present study than in the previous AeroCom study. We find a tendency for models having a strong (positive) BC RF to also have strong (negative) sulphate or OA RF. This relationship leads to smaller uncertainty in the total RF of the DAE compared to the RF of the sum of the individual aerosol components. The spread in results for the individual aerosol components is substantial, and can be divided into diversities in burden, mass extinction coefficient (MEC), and normalized RF with respect to AOD. We find that these three factors give similar contributions to the spread in results.« less

Statistical learning methods for aero-optic wavefront prediction and adaptive-optic latency compensation

NASA Astrophysics Data System (ADS)

Burns, W. Robert

Since the early 1970's research in airborne laser systems has been the subject of continued interest. Airborne laser applications depend on being able to propagate a near diffraction-limited laser beam from an airborne platform. Turbulent air flowing over the aircraft produces density fluctuations through which the beam must propagate. Because the index of refraction of the air is directly related to the density, the turbulent flow imposes aberrations on the beam passing through it. This problem is referred to as Aero-Optics. Aero-Optics is recognized as a major technical issue that needs to be solved before airborne optical systems can become routinely fielded. This dissertation research specifically addresses an approach to mitigating the deleterious effects imposed on an airborne optical system by aero-optics. A promising technology is adaptive optics: a feedback control method that measures optical aberrations and imprints the conjugate aberrations onto an outgoing beam. The challenge is that it is a computationally-difficult problem, since aero-optic disturbances are on the order of kilohertz for practical applications. High control loop frequencies and high disturbance frequencies mean that adaptive-optic systems are sensitive to latency in sensors, mirrors, amplifiers, and computation. These latencies build up to result in a dramatic reduction in the system's effective bandwidth. This work presents two variations of an algorithm that uses model reduction and data-driven predictors to estimate the evolution of measured wavefronts over a short temporal horizon and thus compensate for feedback latency. The efficacy of the two methods are compared in this research, and evaluated against similar algorithms that have been previously developed. The best version achieved over 75% disturbance rejection in simulation in the most optically active flow region in the wake of a turret, considerably outperforming conventional approaches. The algorithm is shown to be

Radiative forcing of the direct aerosol effect from AeroCom Phase II simulations

NASA Astrophysics Data System (ADS)

Myhre, G.; Samset, B. H.; Schulz, M.; Balkanski, Y.; Bauer, S.; Berntsen, T. K.; Bian, H.; Bellouin, N.; Chin, M.; Diehl, T.; Easter, R. C.; Feichter, J.; Ghan, S. J.; Hauglustaine, D.; Iversen, T.; Kinne, S.; Kirkevåg, A.; Lamarque, J.-F.; Lin, G.; Liu, X.; Lund, M. T.; Luo, G.; Ma, X.; van Noije, T.; Penner, J. E.; Rasch, P. J.; Ruiz, A.; Seland, Ø.; Skeie, R. B.; Stier, P.; Takemura, T.; Tsigaridis, K.; Wang, P.; Wang, Z.; Xu, L.; Yu, H.; Yu, F.; Yoon, J.-H.; Zhang, K.; Zhang, H.; Zhou, C.

2013-02-01

We report on the AeroCom Phase II direct aerosol effect (DAE) experiment where 16 detailed global aerosol models have been used to simulate the changes in the aerosol distribution over the industrial era. All 16 models have estimated the radiative forcing (RF) of the anthropogenic DAE, and have taken into account anthropogenic sulphate, black carbon (BC) and organic aerosols (OA) from fossil fuel, biofuel, and biomass burning emissions. In addition several models have simulated the DAE of anthropogenic nitrate and anthropogenic influenced secondary organic aerosols (SOA). The model simulated all-sky RF of the DAE from total anthropogenic aerosols has a range from -0.58 to -0.02 Wm-2, with a mean of -0.27 Wm-2 for the 16 models. Several models did not include nitrate or SOA and modifying the estimate by accounting for this with information from the other AeroCom models reduces the range and slightly strengthens the mean. Modifying the model estimates for missing aerosol components and for the time period 1750 to 2010 results in a mean RF for the DAE of -0.35 Wm-2. Compared to AeroCom Phase I (Schulz et al., 2006) we find very similar spreads in both total DAE and aerosol component RF. However, the RF of the total DAE is stronger negative and RF from BC from fossil fuel and biofuel emissions are stronger positive in the present study than in the previous AeroCom study. We find a tendency for models having a strong (positive) BC RF to also have strong (negative) sulphate or OA RF. This relationship leads to smaller uncertainty in the total RF of the DAE compared to the RF of the sum of the individual aerosol components. The spread in results for the individual aerosol components is substantial, and can be divided into diversities in burden, mass extinction coefficient (MEC), and normalized RF with respect to AOD. We find that these three factors give similar contributions to the spread in results.

Radiative forcing of the direct aerosol effect from AeroCom Phase II simulations

NASA Astrophysics Data System (ADS)

Myhre, G.; Samset, B. H.; Schulz, M.; Balkanski, Y.; Bauer, S.; Berntsen, T. K.; Bian, H.; Bellouin, N.; Chin, M.; Diehl, T.; Easter, R. C.; Feichter, J.; Ghan, S. J.; Hauglustaine, D.; Iversen, T.; Kinne, S.; Kirkevåg, A.; Lamarque, J.-F.; Lin, G.; Liu, X.; Luo, G.; Ma, X.; Penner, J. E.; Rasch, P. J.; Seland, Ø.; Skeie, R. B.; Stier, P.; Takemura, T.; Tsigaridis, K.; Wang, Z.; Xu, L.; Yu, H.; Yu, F.; Yoon, J.-H.; Zhang, K.; Zhang, H.; Zhou, C.

2012-08-01

We report on the AeroCom Phase II direct aerosol effect (DAE) experiment where 15 detailed global aerosol models have been used to simulate the changes in the aerosol distribution over the industrial era. All 15 models have estimated the radiative forcing (RF) of the anthropogenic DAE, and have taken into account anthropogenic sulphate, black carbon (BC) and organic aerosols (OA) from fossil fuel, biofuel, and biomass burning emissions. In addition several models have simulated the DAE of anthropogenic nitrate and anthropogenic influenced secondary organic aerosols (SOA). The model simulated all-sky RF of the DAE from total anthropogenic aerosols has a range from -0.58 to -0.02 W m-2, with a mean of -0.30 W m-2 for the 15 models. Several models did not include nitrate or SOA and modifying the estimate by accounting for this with information from the other AeroCom models reduces the range and slightly strengthens the mean. Modifying the model estimates for missing aerosol components and for the time period 1750 to 2010 results in a mean RF for the DAE of -0.39 W m-2. Compared to AeroCom Phase I (Schulz et al., 2006) we find very similar spreads in both total DAE and aerosol component RF. However, the RF of the total DAE is stronger negative and RF from BC from fossil fuel and biofuel emissions are stronger positive in the present study than in the previous AeroCom study. We find a tendency for models having a strong (positive) BC RF to also have strong (negative) sulphate or OA RF. This relationship leads to smaller uncertainty in the total RF of the DAE compared to the RF of the sum of the individual aerosol components. The spread in results for the individual aerosol components is substantial, and can be divided into diversities in burden, mass extinction coefficient (MEC), and normalized RF with respect to AOD. We find that these three factors give similar contributions to the spread in results.

The Fas/Fap-1/Cav-1 complex regulates IL-1RA secretion in mesenchymal stem cells to accelerate wound healing.

PubMed

Kou, Xiaoxing; Xu, Xingtian; Chen, Chider; Sanmillan, Maria Laura; Cai, Tao; Zhou, Yanheng; Giraudo, Claudio; Le, Anh; Shi, Songtao

2018-03-14

Mesenchymal stem cells (MSCs) are capable of secreting exosomes, extracellular vesicles, and cytokines to regulate cell and tissue homeostasis. However, it is unknown whether MSCs use a specific exocytotic fusion mechanism to secrete exosomes and cytokines. We show that Fas binds with Fas-associated phosphatase-1 (Fap-1) and caveolin-1 (Cav-1) to activate a common soluble N -ethylmaleimide-sensitive factor (NSF) attachment protein receptor (SNARE)-mediated membrane fusion mechanism to release small extracellular vesicles (sEVs) in MSCs. Moreover, we reveal that MSCs produce and secrete interleukin-1 receptor antagonist (IL-1RA) associated with sEVs to maintain rapid wound healing in the gingiva via the Fas/Fap-1/Cav-1 cascade. Tumor necrosis factor-α (TNF-α) serves as an activator to up-regulate Fas and Fap-1 expression via the nuclear factor κB pathway to promote IL-1RA release. This study identifies a previously unknown Fas/Fap-1/Cav-1 axis that regulates SNARE-mediated sEV and IL-1RA secretion in stem cells, which contributes to accelerated wound healing. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

A Mission Concept: Re-Entry Hopper-Aero-Space-Craft System on-Mars (REARM-Mars)

NASA Technical Reports Server (NTRS)

Davoodi, Faranak

2013-01-01

Future missions to Mars that would need a sophisticated lander, hopper, or rover could benefit from the REARM Architecture. The mission concept REARM Architecture is designed to provide unprecedented capabilities for future Mars exploration missions, including human exploration and possible sample-return missions, as a reusable lander, ascend/descend vehicle, refuelable hopper, multiple-location sample-return collector, laboratory, and a cargo system for assets and humans. These could all be possible by adding just a single customized Re-Entry-Hopper-Aero-Space-Craft System, called REARM-spacecraft, and a docking station at the Martian orbit, called REARM-dock. REARM could dramatically decrease the time and the expense required to launch new exploratory missions on Mars by making them less dependent on Earth and by reusing the assets already designed, built, and sent to Mars. REARM would introduce a new class of Mars exploration missions, which could explore much larger expanses of Mars in a much faster fashion and with much more sophisticated lab instruments. The proposed REARM architecture consists of the following subsystems: REARM-dock, REARM-spacecraft, sky-crane, secure-attached-compartment, sample-return container, agile rover, scalable orbital lab, and on-the-road robotic handymen.

Current Progress of a Finite Element Computational Fluid Dynamics Prediction of Flutter for the AeroStructures Test Wing

NASA Technical Reports Server (NTRS)

Arena, Andrew S., Jr.

2002-01-01

This progress report focuses on the use of the STructural Analysis RoutineS suite program, SOLIDS, input for the AeroStructures Test Wing. The AeroStructures Test Wing project as a whole is described. The use of the SOLIDS code to find the mode shapes of a structure is discussed. The frequencies, and the structural dynamics to which they relate are examined. The results of the CFD predictions are compared to experimental data from a Ground Vibration Test.

Formation Flying for Satellites and Unmanned Aerial Vehicles

NASA Technical Reports Server (NTRS)

Merrill, Garrick

2015-01-01

The shrinking size of satellites and unmanned aerial vehicles (UAVs) is enabling lower cost missions. As sensors and electronics continue to downsize, the next step is multiple vehicles providing different perspectives or variations for more precise measurements. While flying a single satellite or UAV autonomously is a challenge, flying multiple vehicles in a precise formation is even more challenging. The goal of this project is to develop a scalable mesh network between vehicles (satellites or UAVs) to share real-time position data and maintain formations autonomously. Newly available low-cost, commercial off-the-shelf credit card size computers will be used as the basis for this network. Mesh networking techniques will be used to provide redundant links and a flexible network. The Small Projects Rapid Integration and Test Environment Lab will be used to simulate formation flying of satellites. UAVs built by the Aero-M team will be used to demonstrate the formation flying in the West Test Area. The ability to test in flight on NASA-owned UAVs allows this technology to achieve a high Technology Readiness Level (TRL) (TRL-4 for satellites and TRL-7 for UAVs). The low cost of small UAVs and the availability of a large test range (West Test Area) dramatically reduces the expense of testing. The end goal is for this technology to be ready to use on any multiple satellite or UAV mission.

Airborne Laser Laboratory departure from Kirtland Air Force Base and a brief history of aero-optics

NASA Astrophysics Data System (ADS)

Kyrazis, Demos T.

2013-07-01

We discuss aspects of the development of the Airborne Laser Laboratory. Our discussion is historical in nature and consists of the text from a speech given on the occasion of the Airborne Laser Laboratory leaving Kirtland Air Force Base (AFB) to fly to Wright-Patterson AFB to become an exhibit at the National Museum of the United States Air Force. The last part of the discussion concerns the inception of the study of aero-optics as an area of research and some of the milestones in the understanding of the causes and prediction of aero-optical effects.

A Rapid Method to Achieve Aero-Engine Blade Form Detection

PubMed Central

Sun, Bin; Li, Bing

2015-01-01

This paper proposes a rapid method to detect aero-engine blade form, according to the characteristics of an aero-engine blade surface. This method first deduces an inclination error model in free-form surface measurements based on the non-contact laser triangulation principle. Then a four-coordinate measuring system was independently developed, a special fixture was designed according to the blade shape features, and a fast measurement of the blade features path was planned. Finally, by using the inclination error model for correction of acquired data, the measurement error that was caused by tilt form is compensated. As a result the measurement accuracy of the Laser Displacement Sensor was less than 10 μm. After the experimental verification, this method makes full use of optical non-contact measurement fast speed, high precision and wide measuring range of features. Using a standard gauge block as a measurement reference, the coordinate system conversion data is simple and practical. It not only improves the measurement accuracy of the blade surface, but also its measurement efficiency. Therefore, this method increases the value of the measurement of complex surfaces. PMID:26039420

A rapid method to achieve aero-engine blade form detection.

PubMed

Sun, Bin; Li, Bing

2015-06-01

This paper proposes a rapid method to detect aero-engine blade form, according to the characteristics of an aero-engine blade surface. This method first deduces an inclination error model in free-form surface measurements based on the non-contact laser triangulation principle. Then a four-coordinate measuring system was independently developed, a special fixture was designed according to the blade shape features, and a fast measurement of the blade features path was planned. Finally, by using the inclination error model for correction of acquired data, the measurement error that was caused by tilt form is compensated. As a result the measurement accuracy of the Laser Displacement Sensor was less than 10 μm. After the experimental verification, this method makes full use of optical non-contact measurement fast speed, high precision and wide measuring range of features. Using a standard gauge block as a measurement reference, the coordinate system conversion data is simple and practical. It not only improves the measurement accuracy of the blade surface, but also its measurement efficiency. Therefore, this method increases the value of the measurement of complex surfaces.

C-Band Airport Surface Communications System Standards Development. Phase II Final Report. Volume 1: Concepts of Use, Initial System Requirements, Architecture, and AeroMACS Design Considerations

NASA Technical Reports Server (NTRS)

Hall, Edward; Isaacs, James; Henriksen, Steve; Zelkin, Natalie

2011-01-01

This report is provided as part of ITT s NASA Glenn Research Center Aerospace Communication Systems Technical Support (ACSTS) contract NNC05CA85C, Task 7: New ATM Requirements-Future Communications, C-Band and L-Band Communications Standard Development and was based on direction provided by FAA project-level agreements for New ATM Requirements-Future Communications. Task 7 included two subtasks. Subtask 7-1 addressed C-band (5091- to 5150-MHz) airport surface data communications standards development, systems engineering, test bed and prototype development, and tests and demonstrations to establish operational capability for the Aeronautical Mobile Airport Communications System (AeroMACS). Subtask 7-2 focused on systems engineering and development support of the L-band digital aeronautical communications system (L-DACS). Subtask 7-1 consisted of two phases. Phase I included development of AeroMACS concepts of use, requirements, architecture, and initial high-level safety risk assessment. Phase II builds on Phase I results and is presented in two volumes. Volume I (this document) is devoted to concepts of use, system requirements, and architecture, including AeroMACS design considerations. Volume II describes an AeroMACS prototype evaluation and presents final AeroMACS recommendations. This report also describes airport categorization and channelization methodologies. The purposes of the airport categorization task were (1) to facilitate initial AeroMACS architecture designs and enable budgetary projections by creating a set of airport categories based on common airport characteristics and design objectives, and (2) to offer high-level guidance to potential AeroMACS technology and policy development sponsors and service providers. A channelization plan methodology was developed because a common global methodology is needed to assure seamless interoperability among diverse AeroMACS services potentially supplied by multiple service providers.

78 FR 1776 - Airworthiness Directives; International Aero Engines AG Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-09

... Engines AG Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of proposed... Aero Engines AG (IAE), V2525-D5 and V2528-D5 turbofan engines, with a certain number (No.) 4 bearing... proposed AD. Discussion We received a report of a fire warning on an IAE V2525 turbofan engine shortly...

Trajectory-Based Loads for the Ares I-X Test Flight Vehicle

NASA Technical Reports Server (NTRS)

Vause, Roland F.; Starr, Brett R.

2011-01-01

In trajectory-based loads, the structural engineer treats each point on the trajectory as a load case. Distributed aero, inertial, and propulsion forces are developed for the structural model which are equivalent to the integrated values of the trajectory model. Free-body diagrams are then used to solve for the internal forces, or loads, that keep the applied aero, inertial, and propulsion forces in dynamic equilibrium. There are several advantages to using trajectory-based loads. First, consistency is maintained between the integrated equilibrium equations of the trajectory analysis and the distributed equilibrium equations of the structural analysis. Second, the structural loads equations are tied to the uncertainty model for the trajectory systems analysis model. Atmosphere, aero, propulsion, mass property, and controls uncertainty models all feed into the dispersions that are generated for the trajectory systems analysis model. Changes in any of these input models will affect structural loads response. The trajectory systems model manages these inputs as well as the output from the structural model over thousands of dispersed cases. Large structural models with hundreds of thousands of degrees of freedom would execute too slowly to be an efficient part of several thousand system analyses. Trajectory-based loads provide a means for the structures discipline to be included in the integrated systems analysis. Successful applications of trajectory-based loads methods for the Ares I-X vehicle are covered in this paper. Preliminary design loads were based on 2000 trajectories using Monte Carlo dispersions. Range safety loads were tied to 8423 malfunction turn trajectories. In addition, active control system loads were based on 2000 preflight trajectories using Monte Carlo dispersions.

Evolved atmospheric entry corridor with safety factor

NASA Astrophysics Data System (ADS)

Liang, Zixuan; Ren, Zhang; Li, Qingdong

2018-02-01

Atmospheric entry corridors are established in previous research based on the equilibrium glide condition which assumes the flight-path angle to be zero. To get a better understanding of the highly constrained entry flight, an evolved entry corridor that considers the exact flight-path angle is developed in this study. Firstly, the conventional corridor in the altitude vs. velocity plane is extended into a three-dimensional one in the space of altitude, velocity, and flight-path angle. The three-dimensional corridor is generated by a series of constraint boxes. Then, based on a simple mapping method, an evolved two-dimensional entry corridor with safety factor is obtained. The safety factor is defined to describe the flexibility of the flight-path angle for a state within the corridor. Finally, the evolved entry corridor is simulated for the Space Shuttle and the Common Aero Vehicle (CAV) to demonstrate the effectiveness of the corridor generation approach. Compared with the conventional corridor, the evolved corridor is much wider and provides additional information. Therefore, the evolved corridor would benefit more to the entry trajectory design and analysis.

Mapped Chebyshev Pseudo-Spectral Method for Dynamic Aero-Elastic Problem of Limit Cycle Oscillation

NASA Astrophysics Data System (ADS)

Im, Dong Kyun; Kim, Hyun Soon; Choi, Seongim

2018-05-01

A mapped Chebyshev pseudo-spectral method is developed as one of the Fourier-spectral approaches and solves nonlinear PDE systems for unsteady flows and dynamic aero-elastic problem in a given time interval, where the flows or elastic motions can be periodic, nonperiodic, or periodic with an unknown frequency. The method uses the Chebyshev polynomials of the first kind for the basis function and redistributes the standard Chebyshev-Gauss-Lobatto collocation points more evenly by a conformal mapping function for improved numerical stability. Contributions of the method are several. It can be an order of magnitude more efficient than the conventional finite difference-based, time-accurate computation, depending on the complexity of solutions and the number of collocation points. The method reformulates the dynamic aero-elastic problem in spectral form for coupled analysis of aerodynamics and structures, which can be effective for design optimization of unsteady and dynamic problems. A limit cycle oscillation (LCO) is chosen for the validation and a new method to determine the LCO frequency is introduced based on the minimization of a second derivative of the aero-elastic formulation. Two examples of the limit cycle oscillation are tested: nonlinear, one degree-of-freedom mass-spring-damper system and two degrees-of-freedom oscillating airfoil under pitch and plunge motions. Results show good agreements with those of the conventional time-accurate simulations and wind tunnel experiments.

High doses of digoxin increase the myocardial nuclear factor-kB and CaV1.2 channels in healthy mice. A possible mechanism of digitalis toxicity.

PubMed

Farghaly, Hanan Sayed Mohamed; Ashry, Israa El-Sayed Mohamed; Hareedy, Mohammad Salem

2018-06-06

Toxic effects of digoxin may occur with normal therapeutic serum level. However, the underlying mechanisms are not fully understood. Nuclear factor kappa-B (NF-kB) is an important transcription factor in most organ systems and is often implicated in the harmful effects of cardiac injury. NF-kB promotes inflammatory responses, mediates adverse cardiac remodeling and has a function correlation with calcium. The voltage-gated L-type calcium channel CaV1.2 mediates the influx of Ca+2 into the cell in response to membrane depolarization. Our aim was to characterize the role of NF-kB during digoxin toxicity and to assess its correlation with Cav 1.2 in healthy mice in vivo. To address these questions, digoxin was administered in doses of 0.1, 1 or 5 mg/kg orally daily for seven days to the animals. Serum digoxin, serum calcium, atrial and ventricular calcium levels were measured. We, also, looked for NF-kB and CaV1.2 channel expression in cardiac muscle of mice. Digoxin at a dose of 0.1 mg/kg did not enhance serum, atrial, and ventricular Ca+2 levels, but were increased when digoxin dose of 1 and 5 mg/kg were administered. Histologically, myocardial necrosis and cellular infiltration on day 7 were significantly more severe in the 5 mg/kg/day digoxin group. Immunohistochemical studies showed more expression of both NF-kB and CaV1.2 in 1 and 5 mg/kg/day digoxin groups. These data suggest that NF-kB may be responsible for digoxin toxicity, at least partially via modulation of CaV1.2 and intracellular calcium homeostasis in the myocardium. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

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

Rios-Torres, Jackeline; Malikopoulos, Andreas A.

Connected and automated vehicles (CAVs) have the potential to improve safety by reducing and mitigating traffic accidents. They can also provide opportunities to reduce transportation energy consumption and emissions by improving traffic flow. Vehicle communication with traffic structures and traffic lights can allow individual vehicles to optimize their operation and account for unpredictable changes. This paper summarizes the developments and the research trends in coordination with the CAVs that have been reported in the literature to date. In conclusion, remaining challenges and potential future research directions are also discussed.

Emergency airway management in critically injured patients: a survey of U.S. aero-medical transport programs.

PubMed

James, Dorsha N; Voskresensky, Igor V; Jack, Meg; Cotton, Bryan A

2009-06-01

Pre-hospital airway management represents the intervention most likely to impact outcomes in critically injured patients. As such, airway management issues dominate quality improvement (QI) reviews of aero-medical programs. The purpose of this study was to evaluate current practice patterns of airway management in trauma among U.S. aero-medical service (AMS) programs. The Association of Air Medical Services (AAMS) Resource Guide from 2005 to 2006 was utilized to identify the e-mail addresses of all directors of U.S. aero-medical transport programs. Program directors from 182 U.S. aero-medical programs were asked to participate in an anonymous, web-based survey of emergency airway management protocols and practices. Non-responders to the initial request were contacted a second time by e-mail. 89 programs responded. 98.9% have rapid sequence intubation (RSI) protocols. 90% use succinylcholine, 70% use long-acting neuromuscular blockers (NMB) within their RSI protocol. 77% have protocols for mandatory in-flight sedation but only 13% have similar protocols for maintenance paralytics. 60% administer long-acting NMB immediately after RSI, 13% after confirmation of neurological activity. Given clinical scenarios, however, 97% administer long-acting NMB to patients with scene and in-flight Glasgow Coma Scale (GCS) of 3, even for brief transport times. The majority of AMS programs have well defined RSI and in-flight sedation protocols, while protocols for in-flight NMB are uncommon. Despite this, nearly all programs administer long-acting NMB following RSI, irrespective of GCS or flight time. Given the impact of in-flight NMB on initial assessment, early intervention, and injury severity scoring, a critical appraisal of current AMS airway management practices appears warranted.

Common Aero Vehicle Autonomous Reentry Trajectory Optimization Satisfying Waypoint and No-Fly Zone Constraints

DTIC Science & Technology

2007-09-01

Control Conference and Exhibit. 5-8 August 2002. AIAA-2002-4457. 25. ElGindy, Hossam and Lachlan Wetherall. “A Simple Voronoi Diagram Algorithm for a...Jacobs, Thomas H., Elan T. Smith , and Michael W. Garrambone. “Space Ac- cess Vehicles Mission and Operations Simulation (SAVMOS) For Simulating

Aero-medical evacuation from the second Israel-Lebanon war: a descriptive study.

PubMed

Schwartz, Dagan; Resheff, Avram; Geftler, Alex; Weiss, Aviram; Birenbaum, Erez; Lavon, Ophir

2009-05-01

The second Lebanon war started as a limited operation and progressed to a large-scale campaign. Most of the fighting took place in mountainous villages and small towns inhabited with civilians. The Israeli Defense Forces (IDF) Airborne rescue and evacuation unit is charged with air evacuation of soldiers and civilians in times of peace, limited conflict, and war. We describe this unit's activities in the second Lebanon war, analyzing injury, treatment, and evacuation characteristics Data were collected from flight medical reports, debriefings of aero-medical team members (usually immediately upon return from mission), ground units medical reports and debriefings, and hospital records. 725 IDF soldiers were injured and 117 killed either in Lebanon or near the Israeli-Lebanese border during the war. A total of 338 (46%) were evacuated in 95 airlifts (averaging 4.5 evacuees per airlift) from the fighting zones or the border. Air evacuation used dedicated helicopters with advanced care capacities, and most victims were evacuated straight from the battlefield, as the fighting was ensuing. Many wounded first received advanced medical care upon the arrival of the aero-medical teams. In military operations within civilian populated areas with threats to ground transport, air evacuation can sometimes be the only readily available option. Providing timely ground advanced medical care proved difficult in many instances. Thus, for many, the rescue helicopter was the first point of access to such care. Aero-medical aircrafts and personnel faced threats from gunfire and missiles, causing both delays in evacuation and a high average number of evacuees per airlift. This article proposes ways of coping with situations in which similar rescue and evacuation problems are likely.

The Calmodulin-Binding, Short Linear Motif, NSCaTE Is Conserved in L-Type Channel Ancestors of Vertebrate Cav1.2 and Cav1.3 Channels

PubMed Central

Taiakina, Valentina; Boone, Adrienne N.; Fux, Julia; Senatore, Adriano; Weber-Adrian, Danielle

2013-01-01

NSCaTE is a short linear motif of (xWxxx(I or L)xxxx), composed of residues with a high helix-forming propensity within a mostly disordered N-terminus that is conserved in L-type calcium channels from protostome invertebrates to humans. NSCaTE is an optional, lower affinity and calcium-sensitive binding site for calmodulin (CaM) which competes for CaM binding with a more ancient, C-terminal IQ domain on L-type channels. CaM bound to N- and C- terminal tails serve as dual detectors to changing intracellular Ca2+ concentrations, promoting calcium-dependent inactivation of L-type calcium channels. NSCaTE is absent in some arthropod species, and is also lacking in vertebrate L-type isoforms, Cav1.1 and Cav1.4 channels. The pervasiveness of a methionine just downstream from NSCaTE suggests that L-type channels could generate alternative N-termini lacking NSCaTE through the choice of translational start sites. Long N-terminus with an NSCaTE motif in L-type calcium channel homolog LCav1 from pond snail Lymnaea stagnalis has a faster calcium-dependent inactivation than a shortened N-termini lacking NSCaTE. NSCaTE effects are present in low concentrations of internal buffer (0.5 mM EGTA), but disappears in high buffer conditions (10 mM EGTA). Snail and mammalian NSCaTE have an alpha-helical propensity upon binding Ca2+-CaM and can saturate both CaM N-terminal and C-terminal domains in the absence of a competing IQ motif. NSCaTE evolved in ancestors of the first animals with internal organs for promoting a more rapid, calcium-sensitive inactivation of L-type channels. PMID:23626724

An Innovative Structural Mode Selection Methodology: Application for the X-33 Launch Vehicle Finite Element Model

NASA Technical Reports Server (NTRS)

Hidalgo, Homero, Jr.

2000-01-01

An innovative methodology for determining structural target mode selection and mode selection based on a specific criterion is presented. An effective approach to single out modes which interact with specific locations on a structure has been developed for the X-33 Launch Vehicle Finite Element Model (FEM). We presented Root-Sum-Square (RSS) displacement method computes resultant modal displacement for each mode at selected degrees of freedom (DOF) and sorts to locate modes with highest values. This method was used to determine modes, which most influenced specific locations/points on the X-33 flight vehicle such as avionics control components, aero-surface control actuators, propellant valve and engine points for use in flight control stability analysis and for flight POGO stability analysis. Additionally, the modal RSS method allows for primary or global target vehicle modes to also be identified in an accurate and efficient manner.

76 FR 77108 - Airworthiness Directives; International Aero Engines Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-12

... Airworthiness Directives; International Aero Engines Turbofan Engines AGENCY: Federal Aviation Administration...-D5, V2530-A5, and V2533-A5 turbofan engines. This AD was prompted by three reports of high- pressure..., V2524-A5, V2525-D5, V2527-A5, V2527E-A5, V2527M-A5, V2528- D5, V2530-A5, and V2533-A5 turbofan engines...

Impact of aeroelasticity on propulsion and longitudinal flight dynamics of an air-breathing hypersonic vehicle

NASA Technical Reports Server (NTRS)

Raney, David L.; Mcminn, John D.; Pototzky, Anthony S.; Wooley, Christine L.

1993-01-01

Many air-breathing hypersonic aerospacecraft design concepts incorporate an elongated fuselage forebody acting as the aerodynamic compression surface for a hypersonic combustion module, or scram jet. This highly integrated design approach creates the potential for an unprecedented form of aero-propulsive-elastic interaction in which deflections of the vehicle fuselage give rise to propulsion transients, producing force and moment variations that may adversely impact the rigid body flight dynamics and/or further excite the fuselage bending modes. To investigate the potential for such interactions, a math model was developed which included the longitudinal flight dynamics, propulsion system, and first seven elastic modes of a hypersonic air-breathing vehicle. Perturbation time histories from a simulation incorporating this math model are presented that quantify the propulsive force and moment variations resulting from aeroelastic vehicle deflections. Root locus plots are presented to illustrate the effect of feeding the propulsive perturbations back into the aeroelastic model. A concluding section summarizes the implications of the observed effects for highly integrated hypersonic air-breathing vehicle concepts.

Impact of aeroelasticity on propulsion and longitudinal flight dynamics of an air-breathing hypersonic vehicle

NASA Astrophysics Data System (ADS)

Raney, David L.; McMinn, John D.; Pototzky, Anthony S.; Wooley, Christine L.

1993-04-01

Many air-breathing hypersonic aerospacecraft design concepts incorporate an elongated fuselage forebody acting as the aerodynamic compression surface for a hypersonic combustion module, or scram jet. This highly integrated design approach creates the potential for an unprecedented form of aero-propulsive-elastic interaction in which deflections of the vehicle fuselage give rise to propulsion transients, producing force and moment variations that may adversely impact the rigid body flight dynamics and/or further excite the fuselage bending modes. To investigate the potential for such interactions, a math model was developed which included the longitudinal flight dynamics, propulsion system, and first seven elastic modes of a hypersonic air-breathing vehicle. Perturbation time histories from a simulation incorporating this math model are presented that quantify the propulsive force and moment variations resulting from aeroelastic vehicle deflections. Root locus plots are presented to illustrate the effect of feeding the propulsive perturbations back into the aeroelastic model. A concluding section summarizes the implications of the observed effects for highly integrated hypersonic air-breathing vehicle concepts.

Results of investigations conducted in the LaRC 4-foot unitary plan wind tunnel leg no. 1 using the 0.010-scale 72-OTS model of the space shuttle integrated vehicle (IA94A)

NASA Technical Reports Server (NTRS)

Nichols, M. E.

1976-01-01

Aero-loads investigations were conducted on the updated configuration-5 space shuttle launch vehicle at Mach numbers 2.50, 3.50, and 4.50. Six-component vehicle forces and moments, base and sting-cavity pressures, elevon hinge moments, wing-root bending and torsion moments, and normal shear force data were obtained. Full simulation of updated vehicle protuberances and attach hardware was employed. Various elevon deflection angles were tested, with two different forward orbiter-to-external-tank attach-strut configurations. The entire vehicle model 72-OTS was supported by means of a balance mounted in the orbiter through its base and suspended from an appropriate sting for the specific tunnel.

78 FR 56589 - Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-13

... friction in the MLG wheel lever sub-assembly. This condition, if not detected and corrected, could lead to...-off or landing runs. To address this potential unsafe condition, Piaggio Aero Industries (PAI) issued... loss of control during take-off or landing runs. (f) Actions and Compliance Unless already done, do the...

Redistribution of Cav2.1 channels and calcium ions in nerve terminals following end-to-side neurorrhaphy: ionic imaging analysis by TOF-SIMS.

PubMed

Liu, Chiung-Hui; Chang, Hung-Ming; Tseng, To-Jung; Lan, Chyn-Tair; Chen, Li-You; Youn, Su-Chung; Lee, Jian-Jr; Mai, Fu-Der; Chou, Jui-Feng; Liao, Wen-Chieh

2016-11-01

The P/Q-type voltage-dependent calcium channel (Cav2.1) in the presynaptic membranes of motor nerve terminals plays an important role in regulating Ca 2+ transport, resulting in transmitter release within the nervous system. The recovery of Ca 2+ -dependent signal transduction on motor end plates (MEPs) and innervated muscle may directly reflect nerve regeneration following peripheral nerve injury. Although the functional significance of calcium channels and the levels of Ca 2+ signalling in nerve regeneration are well documented, little is known about calcium channel expression and its relation with the dynamic Ca 2+ ion distribution at regenerating MEPs. In the present study, end-to-side neurorrhaphy (ESN) was performed as an in vivo model of peripheral nerve injury. The distribution of Ca 2+ at regenerating MEPs following ESN was first detected by time-of-flight secondary ion mass spectrometry, and the specific localization and expression of Cav2.1 channels were examined by confocal microscopy and western blotting. Compared with other fundamental ions, such as Na + and K + , dramatic changes in the Ca 2+ distribution were detected along with the progression of MEP regeneration. The re-establishment of Ca 2+ distribution and intensity were correlated with the functional recovery of muscle in ESN rats. Furthermore, the re-clustering of Cav2.1 channels after ESN at the nerve terminals corresponded with changes in the Ca 2+ distribution. These results indicated that renewal of the Cav2.1 distribution within the presynaptic nerve terminals may be necessary for initiating a proper Ca 2+ influx and shortening the latency of muscle contraction during nerve regeneration.

Effect of folate deficiency on promoter methylation and gene expression of Esr1, Cav1, and Elavl1, and its influence on spermatogenesis.

PubMed

Yuan, Hong-Fang; Zhao, Kai; Zang, Yu; Liu, Chun-Yan; Hu, Zhi-Yong; Wei, Jia-Jing; Zhou, Ting; Li, Ying; Zhang, Hui-Ping

2017-04-11

This study aims to investigate the effect of folate deficiency on the male reproductive function and the underlying mechanism. A total of 269 screened participants from 421 recruitments were enrolled in this study. An animal model of folate deficiency was constructed. Folate concentration was measured in the ejaculate, and its association with semen parameters was then determined. The expression and promoter methylation status of ESR1, CAV1, and ELAVL1 were also evaluated. Results showed that seminal plasma folate level was significantly lower among subjects with azoospermia than those with normozoospermia. Low folate level was significantly correlated with low sperm concentration in men with normozoospermia. Folate deficiency significantly reduced the expression of ESR1, CAV1, and ELAVL1, which are critical to spermatogenesis. However, low folate levels did not increase the methylation levels of the promoter regions of ESR1, CAV1, and ELAVL1 in human sperm DNA. Thus, folate deficiency impairs spermatogenesis may partly due to inhibiting the expression of these genes. Thus future research should determine the significance of sufficient folate status in male fertilization and subsequent pregnancy outcomes.

Results of investigations conducted in the LaRC 8-foot transonic pressure tunnel using the 0.010-scale 72-OTS model of the space shuttle integrated vehicle (IA93)

NASA Technical Reports Server (NTRS)

Nichols, M. E.

1976-01-01

Test procedures, history, and data from the wind tunnel test are presented. Aero-loads were investigated on the updated configuration-5 space shuttle launch vehicle at Mach numbers from 0.600 to 1.205. Six-component vehicle forces and moments, base and sting-cavity pressures, elevon hinge moments, wing-root bending and torsion moments, and normal shear force data were obtained. Full simulation of updated vehicle protuberances and attach hardware was employed. Various elevon deflection angles were tested with two different forward orbiter-to-external-tank attach-strut configurations. The entire model was supported by means of a balance mounted in the orbiter through its base and suspended from a sting.

Attitude Control for an Aero-Vehicle Using Vector Thrusting and Variable Speed Control Moment Gyros

NASA Technical Reports Server (NTRS)

Shin, Jong-Yeob; Lim, K. B.; Moerder, D. D.

2005-01-01

Stabilization of passively unstable thrust-levitated vehicles can require significant control inputs. Although thrust vectoring is a straightforward choice for realizing these inputs, this may lead to difficulties discussed in the paper. This paper examines supplementing thrust vectoring with Variable-Speed Control Moment Gyroscopes (VSCMGs). The paper describes how to allocate VSCMGs and the vectored thrust mechanism for attitude stabilization in frequency domain and also shows trade-off between vectored thrust and VSCMGs. Using an H2 control synthesis methodology in LMI optimization, a feedback control law is designed for a thrust-levitated research vehicle and is simulated with the full nonlinear model. It is demonstrated that VSCMGs can reduce the use of vectored thrust variation for stabilizing the hovering platform in the presence of strong wind gusts.

Design and performance analysis of an aero-maneuvering orbital-transfer vehicle concept

NASA Technical Reports Server (NTRS)

Menees, G. P.

1985-01-01

Systems requirements for design-optimized, lateral-turn performance were determined for reusable, space-based applications and low-Earth orbits involving large multiple plane-inclination changes. The aerothermodynamic analysis is the most advanced available for rarefield-hypersonic flow over lifting surfaces at incidence. The effects of leading-edge bluntness, low-density viscous phenomena, and finite-rate flow-field chemistry and surface catalysis are accounted for. The predicted aerothermal heating characteristics are correlated with thermal-control and flight-performance capabilities. The mission payload capacity for delivery, retrieval, and combined operations was determined for round-trip sorties extending to polar orbits. Recommendations are given for future design refinements. The results help to identify technology issues required to develop prototype operational vehicles.

Aero-Thermo-Dynamic Mass Analysis

NASA Astrophysics Data System (ADS)

Shiba, Kota; Yoshikawa, Genki

2016-07-01

Each gas molecule has its own molecular weight, while such a microscopic characteristic is generally inaccessible, and thus, it is measured indirectly through e.g. ionization in conventional mass analysis. Here, we present a novel approach to the direct measurement of molecular weight through a nanoarchitectonic combination of aerodynamics, thermodynamics, and mechanics, transducing microscopic events into macroscopic phenomena. It is confirmed that this approach can provide molecular weight of virtually any gas or vaporizable liquid sample in real-time without ionization. Demonstrations through analytical calculations, numerical simulations, and experiments verify the validity and versatility of the novel mass analysis realized by a simple setup with a flexible object (e.g. with a bare cantilever and even with a business card) placed in a laminar jet. Owing to its unique and simple working principle, this aero-thermo-dynamic mass analysis (AMA) can be integrated into various analytical devices, production lines, and consumer mobile platforms, opening new chapters in aerodynamics, thermodynamics, mechanics, and mass analysis.

Integrated Aero-Servo-Thermo-Propulso-Elasticity (ASTPE) for Hypersonic Scramjet Vehicle Design/Analysis

DTIC Science & Technology

2009-12-04

heat flux q, see Figure 4.6 - Optimized Weights Winitia, = 0.777 Ibm /ft 2, Wfma! = 0.543 Ibm /ft 2 Shown in Table 4.1 are the optimization results...vehicle: no (0), yes (1), or optimize (2) ideriv - Calculate derivatives: no (0), yes (1) itps - If itps is 1, then prepare for tps and smb. ideriv and... itps cannot be 1 at one time ifeedback - If 1, then gets weight and Cg information from SMB and TPSOPT (1) = height set (1), matrix (2) OUTPUT FILE

Cadmium tolerance and accumulation of Althaea rosea Cav. and its potential as a hyperaccumulator under chemical enhancement.

PubMed

Liu, Jia Nv; Zhou, Qi Xing; Wang, Song; Sun, Ting

2009-02-01

The role of ornamental plants has drawn much attention as the urban pollution levels exacerbate. Althaea rosea Cav. had showed its strong tolerance and accumulation ability of Cd in our previous work, thus, the effects of ethylenediamine triacetic acid (EDTA), ethylenegluatarotriacetic acid (EGTA) and sodium dodecyl sulfate (SDS) on its Cd phytoremediation capacity were further investigated in this work. It reconfirmed that the species had strong tolerance and accumulation ability of Cd. Particularly, the species can be regarded as a potential Cd-hyperaccumulator through applying chemical agents. However, different chelators and surfactants had great differences in affecting hyperaccumulating characteristics of the species. EGTA and SDS could not only increase the dry biomass of the plants, but also promote Cd accumulation in shoots and roots. On the contrary, EDTA was toxic to the species by restraining the growth of plants, although it could promote Cd accumulation in shoots and roots of the plants to a certain extent. Thus, EGTA and SDS were effective in enhancing phytoremediation with Althaea rosea Cav. for Cd contaminated soils, while EDTA is ineffective in this regard.

Dysfunction of the CaV2.1 calcium channel in cerebellar ataxias

PubMed Central

Rajakulendran, Sanjeev; Schorge, Stephanie; Kullmann, Dimitri M

2010-01-01

Mutations in the CACNA1A gene are associated with episodic ataxia type 2 (EA2) and spinocerebellar ataxia type 6 (SCA6). CACNA1A encodes the α-subunit of the P/Q-type calcium channel or CaV2.1, which is highly enriched in the cerebellum. It is one of the main channels linked to synaptic transmission throughout the human central nervous system. Here, we compare recent advances in the understanding of the genetic changes that underlie EA2 and SCA6 and what these new findings suggest about the mechanism of the disease. PMID:20948794

Experimental oral immunization of ferret badgers (Melogale moschata) with a recombinant canine adenovirus vaccine CAV-2-E3Δ-RGP and an attenuated rabies virus SRV9.

PubMed

Zhao, Jinghui; Liu, Ye; Zhang, Shoufeng; Fang, Lijun; Zhang, Fei; Hu, Rongliang

2014-04-01

Ferret badgers (Melogale moschata) are a major reservoir of rabies virus in southeastern China. Oral immunization has been shown to be a practical method for wildlife rabies management in Europe and North America. Two groups of 20 ferret badgers were given a single oral dose of a recombinant canine adenovirus-rabies vaccine, CAV-2-E3Δ-RGP, or an experimental attenuated rabies virus vaccine, SRV9. At 21 days, all ferret badgers had seroconverted, with serum virus-neutralizing antibodies ranging from 0.1 to 4.5 IU/mL. Titers were >0.50 IU/mL (an acceptable level) in 17/20 and 16/20 animals receiving CAV-2-E3Δ-RGP or SRV9, respectively. The serologic results indicate that the recombinant CAV-2-E3Δ-RGP is at least as effective as the attenuated rabies virus vaccine. Both may be considered for additional research as oral rabies vaccine candidates for ferret badgers.

Aero Spacelines B377PG Pregnant Guppy on ramp in preparation for flight tests and pilot evaluation

NASA Technical Reports Server (NTRS)

1962-01-01

The Aero Spacelines B377PG Pregnant Guppy was flown by Aero Spacelines pilots to Dryden for tests and evaluation by pilots Joe Vensel and Stan Butchart in October 1962. The outsized cargo aircraft incorporated the wings, engines, lower fuselage and tail from a Boeing 377 Stratocruiser with a huge upper fuselage more than 20 feet in diameter. The modified aircraft was built to transport outsized cargo for NASA's Apollo program, primarily to carry portions of the Saturn V rockets from the manufacturer to Cape Canaveral. Later versions of the aircraft, including the Super Guppy and the Super Guppy Turbine, are still in use.

PREFACE: 3rd International Conference on Geological, Geographical, Aerospace and Earth Science 2015 (AeroEarth 2015)

NASA Astrophysics Data System (ADS)

Gaol, F. L.

2016-02-01

The 3rd International Conferences on Geological, Geographical, Aerospaces and Earth Sciences 2015 (AeroEarth 2015), was held at The DoubleTree Hilton, Jakarta, Indonesia during 26 - 27 September 2015. The 1st AeoroEarth was held succefully in Jakarta in 2013. The success continued to The 2nd AeroEarth 2014 that was held in Kuta Bali, Indonesia. The publications were published by EES IOP in http://iopscience.iop.org/1755-1315/19/1 and http://iopscience.iop.org/1755-1315/23/1 respectively. The AeroEarth 2015 conference aims to bring together researchers, engineers and scientists from around the world. Through research and development, Earth's scientists have the power to preserve the planet's different resource domains by providing expert opinion and information about the forces which make life possible on Earth. The theme of AeroEarth 2015 is ''Earth and Aerospace Sciences : Challenges and Opportunities'' Earth provides resources and the exact conditions to make life possible. However, with the advent of technology and industrialization, the Earth's resources are being pushed to the brink of depletion. Non-sustainable industrial practices are not only endangering the supply of the Earth's natural resources, but are also putting burden on life itself by bringing about pollution and climate change. A major role of earth science scholars is to examine the delicate balance between the Earth's resources and the growing demands of industrialization. Through research and development, earth scientists have the power to preserve the planet's different resource domains by providing expert opinion and information about the forces which make life possible on Earth. We would like to express our sincere gratitude to all in the Technical Program Committee who have reviewed the papers and developed a very interesting Conference Program as well as the invited and plenary speakers. This year, we received 78 papers and after rigorous review, 18 papers were accepted. The participants

Lockheed Martin approach to a Reusable Launch Vehicle (RLV)

NASA Astrophysics Data System (ADS)

Elvin, John D.

1996-03-01

This paper discusses Lockheed Martin's perspective on the development of a cost effective Reusable Launch Vehicle (RLV). Critical to a successful Single Stage To Orbit (SSTO) program are; an economic development plan sensitive to fiscal constraints; a vehicle concept satisfying present and future US launch needs; and an operations concept commensurate with a market driven program. Participation in the economic plan by government, industry, and the commercial sector is a key element of integrating our development plan and funding profile. The RLV baseline concept design, development evolution and several critical trade studies illustrate the superior performance achieved by our innovative approach to the problem of SSTO. Findings from initial aerodynamic and aerothermodynamic wind tunnel tests and trajectory analyses on this concept confirm the superior characteristics of the lifting body shape combined with the Linear Aerospike rocket engine. This Aero Ballistic Rocket (ABR) concept captures the essence of The Skunk Works approach to SSTO RLV technology integration and system engineering. These programmatic and concept development topics chronicle the key elements to implementing an innovative market driven next generation RLV.

Aero-disaster in Port Harcourt, Nigeria: a case study.

PubMed

Seleye-Fubara, D; Etebu, E N; Amakiri, Cnt

2011-01-01

Aero-disaster in Nigeria is posing a serious problem to government, the public and relatives of victims, as many lives are lost in a single event. A case study based on an incident at an international airport in Nigeria on December 10, 2005. Detailed autopsy was performed on 97 fully identified bodies out of the 106 victims. Variables considered include ages, sex, pattern of injuries and death as well as problems associated with identification of bodies. A total of 97 (91.5%) out of the 106 deaths recorded were autopsied. Nine (8.5%) bodies were beyond identification, and hence autopsy could not be properly done on them. Fifty-nine (60.8%) were males and 38 (39.2%) were females, giving a ratio of 1.4:1. Sixty-one (62.9%) were children and adolescents below the age of 20 years. Severe burns 27 (27.8%), multiple injuries with burns 21 (21.6%), inhalation of fumes 20 (20.6%), multiple injuries only 16 (16.5%), severe head injury alone 11 (11.3%) and ruptured viscous 2 (2.1%) were the causes of death at autopsy in that order of frequency. Aero-disaster, though rare in Port Harcourt, is posing a serious problem in Nigeria in recent times. Various agencies should be established to adequately control mass disasters in Nigeria. Adequate maintenance of aircraft and strict observation and enforcement of aviation laws may drastically reduce the frequency of accidents and subsequent deaths.

Miga Aero Actuator and 2D Machined Mechanical Binary Latch

NASA Technical Reports Server (NTRS)

Gummin, Mark A.

2013-01-01

Shape memory alloy (SMA) actuators provide the highest force-to-weight ratio of any known actuator. They can be designed for a wide variety of form factors from flat, thin packages, to form-matching packages for existing actuators. SMA actuators can be operated many thousands of times, so that ground testing is possible. Actuation speed can be accurately controlled from milliseconds to position and hold, and even electronic velocity-profile control is possible. SMA actuators provide a high degree of operational flexibility, and are truly smart actuators capable of being accurately controlled by onboard microprocessors across a wide range of voltages. The Miga Aero actuator is a SMA actuator designed specifically for spaceflight applications. Providing 13 mm of stroke with either 20- or 40-N output force in two different models, the Aero actuator is made from low-outgassing PEEK (polyether ether ketone) plastic, stainless steel, and nickel-titanium SMA wires. The modular actuator weighs less than 28 grams. The dorsal output attachment allows the Aero to be used in either PUSH or PULL modes by inverting the mounting orientation. The SPA1 actuator utilizes commercially available SMA actuator wire to provide 3/8-in. (approx. =.1 cm) of stroke at a force of over 28 lb (approx. = .125 N). The force is provided by a unique packaging of the single SMA wire that provides the output force of four SMA wires mechanically in parallel. The output load is shared by allowing the SMA wire to slip around the output attachment end to adjust or balance the load, preventing any individual wire segment from experiencing high loads during actuation. A built-in end limit switch prevents overheating of the SMA element following actuation when used in conjunction with the Miga Analog Driver [a simple MOSFET (metal oxide semiconductor field-effect transistor) switching circuit]. A simple 2D machined mechanical binary latch has been developed to complement the capabilities of SMA wire

Apo states of calmodulin and CaBP1 control CaV1 voltage-gated calcium channel function through direct competition for the IQ domain.

PubMed

Findeisen, Felix; Rumpf, Christine H; Minor, Daniel L

2013-09-09

In neurons, binding of calmodulin (CaM) or calcium-binding protein 1 (CaBP1) to the CaV1 (L-type) voltage-gated calcium channel IQ domain endows the channel with diametrically opposed properties. CaM causes calcium-dependent inactivation and limits calcium entry, whereas CaBP1 blocks calcium-dependent inactivation (CDI) and allows sustained calcium influx. Here, we combine isothermal titration calorimetry with cell-based functional measurements and mathematical modeling to show that these calcium sensors behave in a competitive manner that is explained quantitatively by their apo-state binding affinities for the IQ domain. This competition can be completely blocked by covalent tethering of CaM to the channel. Further, we show that Ca(2+)/CaM has a sub-picomolar affinity for the IQ domain that is achieved without drastic alteration of calcium-binding properties. The observation that the apo forms of CaM and CaBP1 compete with each other demonstrates a simple mechanism for direct modulation of CaV1 function and suggests a means by which excitable cells may dynamically tune CaV activity. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Apo-states of calmodulin and CaBP1 control CaV1 voltage-gated calcium channel function through direct competition for the IQ domain

PubMed Central

Findeisen, Felix; Rumpf, Christine; Minor, Daniel L.

2013-01-01

In neurons, binding of calmodulin (CaM) or calcium-binding protein 1 (CaBP1) to the CaV1 (L-type) voltage-gated calcium channel IQ domain endows the channel with diametrically opposed properties. CaM causes calcium-dependent inactivation (CDI) and limits calcium entry, whereas CaBP1 blocks CDI and allows sustained calcium influx. Here, we combine isothermal titration calorimetry (ITC) with cell-based functional measurements and mathematical modeling to show that these calcium sensors behave in a competitive manner that is explained quantitatively by their apo-state binding affinities for the IQ domain. This competition can be completely blocked by covalent tethering of CaM to the channel. Further, we show that Ca2+/CaM has a sub-picomolar affinity for the IQ domain that is achieved without drastic alteration of calcium binding properties. The observation that the apo-forms of CaM and CaBP1 compete with each other demonstrates a simple mechanism for direct modulation of CaV1 function and suggests a means by which excitable cells may dynamically tune CaV activity. PMID:23811053

Modeling C-Band Co-Channel Interference From AeroMACS Omni-Directional Antennas to Mobile Satellite Service Feeder Uplinks

NASA Technical Reports Server (NTRS)

Wilson, Jeffrey D.

2011-01-01

A new C-band (5091 to 5150 MHz) airport communications system designated as Aeronautical Mobile Airport Communications System (AeroMACS) is being planned under the Federal Aviation Administration s NextGen program. An interference analysis software program, Visualyse Professional (Transfinite Systems Ltd), is being utilized to provide guidelines on limitations for AeroMACS transmitters to avoid interference with other systems. A scenario consisting of a single omni-directional transmitting antenna at each of the major contiguous United States airports is modeled and the steps required to build the model are reported. The results are shown to agree very well with a previous study.

The spectral analysis of an aero-engine assembly incorporating a squeeze-film damper

NASA Technical Reports Server (NTRS)

Holmes, R.; Dede, M. M.

1989-01-01

Aero-engine structures have very low inherent damping and so artificial damping is often introduced by pumping oil into annular gaps between the casings and the outer races of some or all of the rolling-element bearings supporting the rotors. The thin oil films so formed are called squeeze film dampers and they can be beneficial in reducing rotor vibration due to unbalance and keeping to reasonable limits the forces transmitted to the engine casing. However, squeeze-film dampers are notoriously non-linear and as a result can introduce into the assembly such phenomena as subharmonic oscillations, jumps and combination frequencies. The purpose of the research is to investigate such phenomena both theoretically and experimentally on a test facility reproducing the essential features of a medium-size aero engine. The forerunner of this work was published. It was concerned with the examination of a squeeze-film damper in series with housing flexibility when supporting a rotor. The structure represented to a limited extent the essentials of the projected Rolls Royce RB401 engine. That research demonstrated the ability to calculate the oil-film forces arising from the squeeze film from known motions of the bearing components and showed that the dynamics of a shaft fitted with a squeeze film bearing can be predicted reasonably accurately. An aero-engine will normally have at least two shafts and so in addition to the excitation forces which are synchronous with the rotation of one shaft, there will also be forces at other frequencies from other shafts operating on the squeeze-film damper. Theoretical and experimental work to consider severe loading of squeeze-film dampers and to include these additional effects are examined.

Accumulating Evidence and Research Organization (AERO) model: a new tool for representing, analyzing, and planning a translational research program.

PubMed

Hey, Spencer Phillips; Heilig, Charles M; Weijer, Charles

2013-05-30

Maximizing efficiency in drug development is important for drug developers, policymakers, and human subjects. Limited funds and the ethical imperative of risk minimization demand that researchers maximize the knowledge gained per patient-subject enrolled. Yet, despite a common perception that the current system of drug development is beset by inefficiencies, there remain few approaches for systematically representing, analyzing, and communicating the efficiency and coordination of the research enterprise. In this paper, we present the first steps toward developing such an approach: a graph-theoretic tool for representing the Accumulating Evidence and Research Organization (AERO) across a translational trajectory. This initial version of the AERO model focuses on elucidating two dimensions of robustness: (1) the consistency of results among studies with an identical or similar outcome metric; and (2) the concordance of results among studies with qualitatively different outcome metrics. The visual structure of the model is a directed acyclic graph, designed to capture these two dimensions of robustness and their relationship to three basic questions that underlie the planning of a translational research program: What is the accumulating state of total evidence? What has been the translational trajectory? What studies should be done next? We demonstrate the utility of the AERO model with an application to a case study involving the antibacterial agent, moxifloxacin, for the treatment of drug-susceptible tuberculosis. We then consider some possible elaborations for the AERO model and propose a number of ways in which the tool could be used to enhance the planning, reporting, and analysis of clinical trials. The AERO model provides an immediate visual representation of the number of studies done at any stage of research, depicting both the robustness of evidence and the relationship of each study to the larger translational trajectory. In so doing, it makes some of the

Simulating Global AeroMACS Airport Ground Station Antenna Power Transmission Limits to Avoid Interference With Mobile Satellite Service Feeder Uplinks

NASA Technical Reports Server (NTRS)

Wilson, Jeffrey D.

2013-01-01

The Aeronautical Mobile Airport Communications System (AeroMACS), which is based upon the IEEE 802.16e mobile wireless standard, is expected to be implemented in the 5091 to 5150 MHz frequency band. As this band is also occupied by Mobile Satellite Service feeder uplinks, AeroMACS must be designed to avoid interference with this incumbent service. The aspects of AeroMACS operation that present potential interference are under analysis in order to enable the definition of standards that assure that such interference will be avoided. In this study, the cumulative interference power distribution at low Earth orbit from transmitters at global airports was simulated with the Visualyse Professional software. The dependence of the interference power on antenna distribution, gain patterns, duty cycle, and antenna tilt was simulated. As a function of these parameters, the simulation results are presented in terms of the limitations on transmitter power from global airports required to maintain the cumulative interference power under the established threshold.

Cross-Correlations and Structures of Aero-Engine Gas Path System Based on DCCA Coefficient and Rooted Tree

NASA Astrophysics Data System (ADS)

Dong, Keqiang; Fan, Jie; Gao, You

2015-12-01

Identifying the mutual interaction is a crucial problem that facilitates the understanding of emerging structures in complex system. We here focus on aero-engine dynamic as an example of complex system. By applying the detrended cross-correlation analysis (DCCA) coefficient method to aero-engine gas path system, we find that the low-spool rotor speed (N1) and high-spool rotor speed (N2) fluctuation series exhibit cross-correlation characteristic. Further, we employ detrended cross-correlation coefficient matrix and rooted tree to investigate the mutual interactions of other gas path variables. The results can infer that the exhaust gas temperature (EGT), N1, N2, fuel flow (WF) and engine pressure ratio (EPR) are main gas path parameters.

Electrophysiological characterization of activation state-dependent Ca(v)2 channel antagonist TROX-1 in spinal nerve injured rats.

PubMed

Patel, R; Rutten, K; Valdor, M; Schiene, K; Wigge, S; Schunk, S; Damann, N; Christoph, T; Dickenson, A H

2015-06-25

Prialt, a synthetic version of Ca(v)2.2 antagonist ω-conotoxin MVIIA derived from Conus magus, is the first clinically approved voltage-gated calcium channel blocker for refractory chronic pain. However, due to the narrow therapeutic window and considerable side effects associated with systemic dosing, Prialt is only administered intrathecally. N-triazole oxindole (TROX-1) is a novel use-dependent and activation state-selective small-molecule inhibitor of Ca(v)2.1, 2.2 and 2.3 calcium channels designed to overcome the limitations of Prialt. We have examined the neurophysiological and behavioral effects of blocking calcium channels with TROX-1. In vitro, TROX-1, in contrast to state-independent antagonist Prialt, preferentially inhibits Ca(v)2.2 currents in rat dorsal root ganglia (DRG) neurons under depolarized conditions. In vivo electrophysiology was performed to record from deep dorsal horn lamina V/VI wide dynamic range neurons in non-sentient spinal nerve-ligated (SNL) and sham-operated rats. In SNL rats, spinal neurons exhibited reduced responses to innocuous and noxious punctate mechanical stimulation of the receptive field following subcutaneous administration of TROX-1, an effect that was absent in sham-operated animals. No effect was observed on neuronal responses evoked by dynamic brushing, heat or cold stimulation in SNL or sham rats. The wind-up response of spinal neurons following repeated electrical stimulation of the receptive field was also unaffected. Spinally applied TROX-1 dose dependently inhibited mechanically evoked neuronal responses in SNL but not sham-operated rats, consistent with behavioral observations. This study confirms the pathological state-dependent actions of TROX-1 through a likely spinal mechanism and reveals a modality selective change in calcium channel function following nerve injury. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

X-ray Photoelectron Spectroscopy study of CaV1-xMoxO3-δ

NASA Astrophysics Data System (ADS)

Belyakov, S. A.; Kuznetsov, M. V.; Shkerin, S. N.

2018-06-01

An investigation was carried out on perovskite-based derivatives of CaV1-xMoxO3-δ using X-ray Photoelectron Spectroscopy (XPS). According to the XRD pattern, the area of homogeneity covers the region from x = 0 to x = 0.6. Wide XPS-peaks of Ca, V, Mo and O are observed, signalling that elements are presented in multiple states. A model for explaining the large chemical shifts of XPS peaks due to different charging effects on different parts of the sample surface is proposed.

Turbine Inlet Air Cooling for Industrial and Aero-derivative Gas Turbine in Malaysia Climate

NASA Astrophysics Data System (ADS)

Nordin, A.; Salim, D. A.; Othoman, M. A.; Kamal, S. N. Omar; Tam, Danny; Yusof, M. KY

2017-12-01

The performance of a gas turbine is dependent on the ambient temperature. A higher temperature results in a reduction of the gas turbine’s power output and an increase in heat rate. The warm and humid climate in Malaysia with its high ambient air temperature has an adverse effect on the performance of gas turbine generators. In this paper, the expected effect of turbine inlet air cooling technology on the annual performance of an aero-derivative gas turbine (GE LM6000PD) is compared against that of an industrial gas turbine (GEFr6B.03) using GT Pro software. This study investigated the annual net energy output and the annual net electrical efficiency of a plant with and without turbine inlet air cooling technology. The results show that the aero-derivative gas turbine responds more favorably to turbine inlet air cooling technology, thereby yielding higher annual net energy output and higher net electrical efficiency when compared to the industrial gas turbine.

76 FR 82202 - Airworthiness Directives; International Aero Engines AG Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-30

... Engines AG Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of proposed... International Aero Engines AG (IAE) V2500-A1, V2525-D5 and V2528-D5 turbofan engines, and certain serial numbers (S/Ns) of IAE V2522-A5, V2524-A5, V2527-A5, V2527E-A5, V2527M-A5, V2530-A5, and V2533-A5 turbofan...

Analysis of MMIC arrays for use in the ACTS Aero Experiment

NASA Technical Reports Server (NTRS)

Zimmerman, M.; Lee, R.; Rho, E.; Zaman, Z.

1993-01-01

The Aero Experiment is designed to demonstrate communication from an aircraft to an Earth terminal via the ACTS. This paper describes the link budget and antenna requirements for a 4.8 kbps full-duplex voice link at Ka-Band frequencies. Three arrays, one transmit array developed by TI and two receive arrays developed by GE and Boeing, were analyzed. The predicted performance characteristics of these arrays are presented and discussed in the paper.

Evaluation of aero commander propeller acoustic data: Taxi operations

NASA Technical Reports Server (NTRS)

Piersol, A. G.; Wilby, E. G.; Wilby, J. F.

1979-01-01

The acoustic data from ground tests performed on an Aero Commander propeller driven aircraft are analyzed. An array of microphones flush mounted on the side of the fuselage were used to record data. The propeller blade passage noise during operations at several different taxi speeds is considered and calculations of the magnitude and phase of the blade passage tones, the amplitude stability of the tones, and the spatial phase and coherence of the tones are included. The measured results are compared to theoretical predictions for propeller noise and various evaluations which reveal important details of propeller noise characteristics are presented.

Aero-acoustics of Drag Generating Swirling Exhaust Flows

NASA Technical Reports Server (NTRS)

Shah, P. N.; Mobed, D.; Spakovszky, Z. S.; Brooks, T. F.; Humphreys, W. M. Jr.

2007-01-01

Aircraft on approach in high-drag and high-lift configuration create unsteady flow structures which inherently generate noise. For devices such as flaps, spoilers and the undercarriage there is a strong correlation between overall noise and drag such that, in the quest for quieter aircraft, one challenge is to generate drag at low noise levels. This paper presents a rigorous aero-acoustic assessment of a novel drag concept. The idea is that a swirling exhaust flow can yield a steady, and thus relatively quiet, streamwise vortex which is supported by a radial pressure gradient responsible for pressure drag. Flows with swirl are naturally limited by instabilities such as vortex breakdown. The paper presents a first aero-acoustic assessment of ram pressure driven swirling exhaust flows and their associated instabilities. The technical approach combines an in-depth aerodynamic analysis, plausibility arguments to qualitatively describe the nature of acoustic sources, and detailed, quantitative acoustic measurements using a medium aperture directional microphone array in combination with a previously established Deconvolution Approach for Mapping of Acoustic Sources (DAMAS). A model scale engine nacelle with stationary swirl vanes was designed and tested in the NASA Langley Quiet Flow Facility at a full-scale approach Mach number of 0.17. The analysis shows that the acoustic signature is comprised of quadrupole-type turbulent mixing noise of the swirling core flow and scattering noise from vane boundary layers and turbulent eddies of the burst vortex structure near sharp edges. The exposed edges are the nacelle and pylon trailing edge and the centerbody supporting the vanes. For the highest stable swirl angle setting a nacelle area based drag coefficient of 0.8 was achieved with a full-scale Overall Sound Pressure Level (OASPL) of about 40dBA at the ICAO approach certification point.

Experimental investigation on aero-optical aberration of shock wave/boundary layer interactions

NASA Astrophysics Data System (ADS)

Ding, Haolin; Yi, Shihe; Fu, Jia; He, Lin

2016-10-01

After streaming through the flow field which including the expansion, shock wave, boundary, etc., the optical wave would be distorted by fluctuations in the density field. Interactions between laminar/turbulent boundary layer and shock wave contain large number complex flow structures, which offer a condition for studying the influences that different flow structures of the complex flow field have on the aero-optical aberrations. Interactions between laminar/turbulent boundary layer and shock wave are investigated in a Mach 3.0 supersonic wind tunnel, based on nanoparticle-tracer planar laser scattering (NPLS) system. Boundary layer separation/attachment, induced suppression waves, induced shock wave, expansion fan and boundary layer are presented by NPLS images. Its spatial resolution is 44.15 μm/pixel. Time resolution is 6ns. Based on the NPLS images, the density fields with high spatial-temporal resolution are obtained by the flow image calibration, and then the optical path difference (OPD) fluctuations of the original 532nm planar wavefront are calculated using Ray-tracing theory. According to the different flow structures in the flow field, four parts are selected, (1) Y=692 600pixel; (2) Y=600 400pixel; (3) Y=400 268pixel; (4) Y=268 0pixel. The aerooptical effects of different flow structures are quantitatively analyzed, the results indicate that: the compressive waves such as incident shock wave, induced shock wave, etc. rise the density, and then uplift the OPD curve, but this kind of shock are fixed in space position and intensity, the aero-optics induced by it can be regarded as constant; The induced shock waves are induced by the coherent structure of large size vortex in the interaction between turbulent boundary layer, its unsteady characteristic decides the induced waves unsteady characteristic; The space position and intensity of the induced shock wave are fixed in the interaction between turbulent boundary layer; The boundary layer aero-optics are

76 FR 36980 - Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Model PIAGGIO P-180 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-24

... Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Model PIAGGIO P-180 Airplanes AGENCY: Federal Aviation... Management Facility between 9 a.m. and 5 p.m., Monday through Friday, except Federal holidays. The AD docket...-P ...

Digital holographic interferometry for characterizing deformable mirrors in aero-optics

NASA Astrophysics Data System (ADS)

Trolinger, James D.; Hess, Cecil F.; Razavi, Payam; Furlong, Cosme

2016-08-01

Measuring and understanding the transient behavior of a surface with high spatial and temporal resolution are required in many areas of science. This paper describes the development and application of a high-speed, high-dynamic range, digital holographic interferometer for high-speed surface contouring with fractional wavelength precision and high-spatial resolution. The specific application under investigation here is to characterize deformable mirrors (DM) employed in aero-optics. The developed instrument was shown capable of contouring a deformable mirror with extremely high-resolution at frequencies exceeding 40 kHz. We demonstrated two different procedures for characterizing the mechanical response of a surface to a wide variety of input forces, one that employs a high-speed digital camera and a second that employs a low-speed, low-cost digital camera. The latter is achieved by cycling the DM actuators with a step input, producing a transient that typically lasts up to a millisecond before reaching equilibrium. Recordings are made at increasing times after the DM initiation from zero to equilibrium to analyze the transient. Because the wave functions are stored and reconstructable, they can be compared with each other to produce contours including absolute, difference, and velocity. High-speed digital cameras recorded the wave functions during a single transient at rates exceeding 40 kHz. We concluded that either method is fully capable of characterizing a typical DM to the extent required by aero-optical engineers.

The Role of Guidance, Navigation, and Control in Hypersonic Vehicle Multidisciplinary Design and Optimization

NASA Technical Reports Server (NTRS)

Ouzts, Peter J.; Soloway, Donald I.; Moerder, Daniel D.; Wolpert, David H.; Benavides, Jose Victor

2009-01-01

Airbreathing hypersonic systems offer distinct performance advantages over rocket-based systems for space access vehicles. However, these performance advantages are dependent upon advances in current state-of-the-art technologies in many areas such as ram/scramjet propulsion integration, high temperature materials, aero-elastic structures, thermal protection systems, transition to hypersonics and hypersonic control elements within the framework of complex physics and new design methods. The complex interactions between elements of an airbreathing hypersonic vehicle represent a new paradigm in vehicle design to achieve the optimal performance necessary to meet space access mission objectives. In the past, guidance, navigation, and control (GNC) analysis often follows completion of the vehicle conceptual design process. Individual component groups design subsystems which are then integrated into a vehicle configuration. GNC is presented the task of developing control approaches to meet vehicle performance objectives given that configuration. This approach may be sufficient for vehicles where significant performance margins exist. However, for higher performance vehicles engaging the GNC discipline too late in the design cycle has been costly. For example, the X-29 experimental flight vehicle was built as a technology demonstrator. One of the many technologies to be demonstrated was the use of light-weight material composites for structural components. The use of light-weight materials increased the flexibility of the X- 29 beyond that of conventional metal alloy constructed aircraft. This effect was not considered when the vehicle control system was designed and built. The impact of this is that the control system did not have enough control authority to compensate for the effects of the first fundamental structural mode of the vehicle. As a result, the resulting pitch rate response of the vehicle was below specification and no post-design changes could recover the

Future NASA Power Technologies for Space and Aero Propulsion Applications

NASA Technical Reports Server (NTRS)

Soeder, James F.

2015-01-01

To achieve the ambitious goals that NASA has outlined for the next decades considerable development of power technology will be necessary. This presentation outlines the development objectives for both space and aero applications. It further looks at the various power technologies that support these objectives and examines drivers that will be a driving force for future development. Finally, the presentation examines what type of non-traditional learning areas should be emphasized in student curriculum so that the engineering needs of the third decade of the 21st Century are met.

Numerical study on influence of single control surface on aero elastic behavior of forward-swept wing

NASA Astrophysics Data System (ADS)

Wang, Ning; Su, Xinbing; Ma, Binlin; Zhang, Xiaofei

2017-10-01

In order to study the influence of elastic forward-swept wing (FSW) with single control surface, the computational fluid dynamics/computational structural dynamics (CFD/CSD) loose coupling static aero elastic numerical calculation method was adopted for numerical simulation. The effects of the elastic FSW with leading- or trailing-edge control surface on aero elastic characteristics were calculated and analysed under the condition of high subsonic speed. The result shows that, the deflection of every single control surface could change the aero elastic characteristics of elastic FSW greatly. Compared with the baseline model, when leading-edge control surface deflected up, under the condition of small angles of attack, the aerodynamic characteristics was poor, but the bending and torsional deformation decreased. Under the condition of moderate angles of attack, the aerodynamic characteristics was improved, but bending and torsional deformation increased; When leading-edge control surface deflected down, the aerodynamic characteristics was improved, the bending and torsional deformation decreased/increased under the condition of small/moderate angles of attack. Compared with the baseline model, when trailing-edge control surface deflected down, the aerodynamic characteristics was improved. The bending and torsional deformation increased under the condition of small angles of attack. The bending deformation increased under the condition of small angles of attack, but torsional deformation decreases under the condition of moderate angles of attack. So, for the elastic FSW, the deflection of trailing-edge control surface play a more important role on the improvement of aerodynamic and elastic deformation characteristics.

Overview of Orion Crew Module and Launch Abort Vehicle Dynamic Stability

NASA Technical Reports Server (NTRS)

Owens, Donald B.; Aibicjpm. Vamessa V.

2011-01-01

With the retirement of the Space Shuttle, NASA is designing a new spacecraft, called Orion, to fly astronauts to low earth orbit and beyond. Characterization of the dynamic stability of the Orion spacecraft is important for the design of the spacecraft and trajectory construction. Dynamic stability affects the stability and control of the Orion Crew Module during re-entry, especially below Mach = 2.0 and including flight under the drogues. The Launch Abort Vehicle is affected by dynamic stability as well, especially during the re-orientation and heatshield forward segments of the flight. The dynamic stability was assessed using the forced oscillation technique, free-to-oscillate, ballistic range, and sub-scale free-flight tests. All of the test techniques demonstrated that in heatshield-forward flight the Crew Module and Launch Abort Vehicle are dynamically unstable in a significant portion of their flight trajectory. This paper will provide a brief overview of the Orion dynamic aero program and a high-level summary of the dynamic stability characteristics of the Orion spacecraft.

PREFACE: The 2nd International Conference on Geological, Geographical, Aerospace and Earth Sciences 2014 (AeroEarth 2014)

NASA Astrophysics Data System (ADS)

Lumban Gaol, Ford; Soewito, Benfano

2015-01-01

The 2nd International Conference on Geological, Geographical, Aerospace and Earth Sciences 2014 (AeroEarth 2014), was held at Discovery Kartika Plaza Hotel, Kuta, Bali, Indonesia during 11 - 12 October 2014. The AeroEarth 2014 conference aims to bring together researchers and engineers from around the world. Through research and development, earth scientists have the power to preserve the planet's different resource domains by providing expert opinion and information about the forces which make life possible on Earth. Earth provides resources and the exact conditions to make life possible. However, with the advent of technology and industrialization, the Earth's resources are being pushed to the brink of depletion. Non-sustainable industrial practices are not only endangering the supply of the Earth's natural resources, but are also putting burden on life itself by bringing about pollution and climate change. A major role of earth science scholars is to examine the delicate balance between the Earth's resources and the growing demands of industrialization. Through research and development, earth scientists have the power to preserve the planet's different resource domains by providing expert opinion and information about the forces which make life possible on Earth. We would like to express our sincere gratitude to all in the Technical Program Committee who have reviewed the papers and developed a very interesting Conference Program as well as the invited and plenary speakers. This year, we received 98 papers and after rigorous review, 17 papers were accepted. The participants come from eight countries. There are four Parallel Sessions and two invited Speakers. It is an honour to present this volume of IOP Conference Series: Earth and Environmental Science (EES) and we deeply thank the authors for their enthusiastic and high-grade contributions. Finally, we would like to thank the conference chairmen, the members of the steering committee, the organizing committee

Aero-Propulsion Technology (APT) Task V Low Noise ADP Engine Definition Study

NASA Technical Reports Server (NTRS)

Holcombe, V.

2003-01-01

A study was conducted to identify and evaluate noise reduction technologies for advanced ducted prop propulsion systems that would allow increased capacity operation and result in an economically competitive commercial transport. The study investigated the aero/acoustic/structural advancements in fan and nacelle technology required to match or exceed the fuel burned and economic benefits of a constrained diameter large Advanced Ducted Propeller (ADP) compared to an unconstrained ADP propulsion system with a noise goal of 5 to 10 EPNDB reduction relative to FAR 36 Stage 3 at each of the three measuring stations namely, takeoff (cutback), approach and sideline. A second generation ADP was selected to operate within the maximum nacelle diameter constrain of 160 deg to allow installation under the wing. The impact of fan and nacelle technologies of the second generation ADP on fuel burn and direct operating costs for a typical 3000 nm mission was evaluated through use of a large, twin engine commercial airplane simulation model. The major emphasis of this study focused on fan blade aero/acoustic and structural technology evaluations and advanced nacelle designs. Results of this study have identified the testing required to verify the interactive performance of these components, along with noise characteristics, by wind tunnel testing utilizing and advanced interaction rig.

The novel product of a five-exon stargazin-related gene abolishes CaV2.2 calcium channel expression

PubMed Central

Moss, Fraser J.; Viard, Patricia; Davies, Anthony; Bertaso, Federica; Page, Karen M.; Graham, Alex; Cantí, Carles; Plumpton, Mary; Plumpton, Christopher; Clare, Jeffrey J.; Dolphin, Annette C.

2002-01-01

We have cloned and characterized a new member of the voltage-dependent Ca2+ channel γ subunit family, with a novel gene structure and striking properties. Unlike the genes of other potential γ subunits identified by their homology to the stargazin gene, CACNG7 is a five-, and not four-exon gene whose mRNA encodes a protein we have designated γ7. Expression of human γ7 has been localized specifically to brain. N-type current through CaV2.2 channels was almost abolished when co-expressed transiently with γ7 in either Xenopus oocytes or COS-7 cells. Furthermore, immunocytochemistry and western blots show that γ7 has this effect by causing a large reduction in expression of CaV2.2 rather than by interfering with trafficking or biophysical properties of the channel. No effect of transiently expressed γ7 was observed on pre-existing endogenous N-type calcium channels in sympathetic neurones. Low homology to the stargazin-like γ subunits, different gene structure and the unique functional properties of γ7 imply that it represents a distinct subdivision of the family of proteins identified by their structural and sequence homology to stargazin. PMID:11927536

Interaction between amiodarone and hepatitis-C virus nucleotide inhibitors in human induced pluripotent stem cell-derived cardiomyocytes and HEK-293 Cav1.2 over-expressing cells.

PubMed

Lagrutta, Armando; Zeng, Haoyu; Imredy, John; Balasubramanian, Bharathi; Dech, Spencer; Lis, Edward; Wang, Jixin; Zhai, Jin; DeGeorge, Joseph; Sannajust, Frederick

2016-10-01

Several clinical cases of severe bradyarrhythmias have been reported upon co-administration of the Hepatitis-C NS5B Nucleotide Polymerase Inhibitor (HCV-NI) direct-acting antiviral agent, sofosbuvir (SOF), and the Class-III anti-arrhythmic amiodarone (AMIO). We model the cardiac drug-drug interaction (DDI) between AMIO and SOF, and between AMIO and a closely-related SOF analog, MNI-1 (Merck Nucleotide Inhibitor #1), in functional assays of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), to provide mechanistic insights into recently reported clinical cases. AMIO co-applied with SOF or MNI-1 increased beating rate or field potential (FP) rate and decreased impedance (IMP) and Ca(2+) transient amplitudes in hiPSC-CM syncytia. This action resembled that of Ca(2+) channel blockers (CCBs) in the model, but CCBs did not substitute for AMIO in the DDI. AMIO analog dronedarone (DRON) did not substitute for, but competed with AMIO in the DDI. Ryanodine and thapsigargin, decreasing intracellular Ca(2+) stores, and SEA-0400, a Na(+)/Ca(2+) exchanger-1 (NCX1) inhibitor, partially antagonized or suppressed DDI effects. Other agents affecting FP rate only exerted additive or subtractive effects, commensurate with their individual effects. We also describe an interaction between AMIO and MNI-1 on Cav1.2 ion channels in an over-expressing HEK-293 cell line. MNI-1 enhanced Cav1.2 channel inhibition by AMIO, but did not affect inhibition of Cav1.2 by DRON, verapamil, nifedipine, or diltiazem. Our data in hiPSC-CMs indicate that HCV-NI agents such as SOF and MNI-1 interact with key intracellular Ca(2+)-handling mechanisms. Additional study in a Cav1.2 HEK-293 cell-line suggests that HCV-NIs potentiate the inhibitory action of AMIO on L-type Ca(2+) channels. Copyright © 2016 Elsevier Inc. All rights reserved.

The Design and Semi-Physical Simulation Test of Fault-Tolerant Controller for Aero Engine

NASA Astrophysics Data System (ADS)

Liu, Yuan; Zhang, Xin; Zhang, Tianhong

2017-11-01

A new fault-tolerant control method for aero engine is proposed, which can accurately diagnose the sensor fault by Kalman filter banks and reconstruct the signal by real-time on-board adaptive model combing with a simplified real-time model and an improved Kalman filter. In order to verify the feasibility of the method proposed, a semi-physical simulation experiment has been carried out. Besides the real I/O interfaces, controller hardware and the virtual plant model, semi-physical simulation system also contains real fuel system. Compared with the hardware-in-the-loop (HIL) simulation, semi-physical simulation system has a higher degree of confidence. In order to meet the needs of semi-physical simulation, a rapid prototyping controller with fault-tolerant control ability based on NI CompactRIO platform is designed and verified on the semi-physical simulation test platform. The result shows that the controller can realize the aero engine control safely and reliably with little influence on controller performance in the event of fault on sensor.

Modular Aero-Propulsion System Simulation

NASA Technical Reports Server (NTRS)

Parker, Khary I.; Guo, Ten-Huei

2006-01-01

The Modular Aero-Propulsion System Simulation (MAPSS) is a graphical simulation environment designed for the development of advanced control algorithms and rapid testing of these algorithms on a generic computational model of a turbofan engine and its control system. MAPSS is a nonlinear, non-real-time simulation comprising a Component Level Model (CLM) module and a Controller-and-Actuator Dynamics (CAD) module. The CLM module simulates the dynamics of engine components at a sampling rate of 2,500 Hz. The controller submodule of the CAD module simulates a digital controller, which has a typical update rate of 50 Hz. The sampling rate for the actuators in the CAD module is the same as that of the CLM. MAPSS provides a graphical user interface that affords easy access to engine-operation, engine-health, and control parameters; is used to enter such input model parameters as power lever angle (PLA), Mach number, and altitude; and can be used to change controller and engine parameters. Output variables are selectable by the user. Output data as well as any changes to constants and other parameters can be saved and reloaded into the GUI later.

Pregabalin Modulation of Neurotransmitter Release Is Mediated by Change in Intrinsic Activation/Inactivation Properties of Cav2.1 Calcium ChannelsS⃞

PubMed Central

Di Guilmi, Mariano N.; Urbano, Francisco J.; Inchauspe, Carlota Gonzalez

2011-01-01

In this work, we studied the effects of the anticonvulsant and analgesic drug pregabalin (PGB) on excitatory postsynaptic currents (EPSCs) at principal neurons of the mouse medial nucleus of the trapezoid body and on presynaptic calcium currents at the calyx of Held. We found that the acute application of PGB reduced the amplitude of EPSCs in a dose-dependent manner with a maximal blocking effect of approximately 30%. A clinical high-concentration dose of PGB (e.g., 500 μM) blocked Cav2.1 channel-mediated currents and decreased their facilitation during a 100-Hz train, without changing their voltage-dependent activation. Furthermore, PGB also removed the inactivation of Cav2.1 channels at a clinically relevant low concentration of 100 μM. These results suggest novel modulatory mechanisms mediated by the acute administration of PGB on fast excitatory synaptic transmission and might contribute to better understanding PGB anticonvulsant/analgesic clinical effects. PMID:21177783

Effect of protein tyrosine kinase inhibitors on the current through the Ca(V)3.1 channel.

PubMed

Kurejová, Martina; Lacinová, L'ubica

2006-02-01

In the present study, we have investigated the effects of protein tyrosine kinase (PTK) inhibitors on the Ca(V)3.1 calcium channel stably transfected in HEK293 cells using the whole-cell configuration of the patch-clamp technique. We have tested two different tyrosine kinase inhibitors, genistein and tyrphostin AG213, and their inactive analogs, genistin and tyrphostin AG9. Bath application of genistein, but not genistin, decreased the T-type calcium current amplitude in a concentration-dependent manner with an IC(50) of 24.7+/-2.0 microM. This effect of genistein was accompanied by deceleration of channel activation and acceleration of channel inactivation. Intracellular application of neither genistein nor genistin had a significant effect on the calcium current. Extracellular application of 50 microM tyrphostin AG213 and its inactive analogue, tyrphostin AG9, did not affect the current through the Ca(V)3.1 channel. The effect of genistein on the channel was also not affected by the presence of catalytically active PTK, p60(c-src) inside the cell. We have concluded that genistein directly inhibited the channel. This mechanism does not involve a PTK-dependent pathway. The alteration of the channel kinetics by genistein suggests an interaction with the voltage sensor of the channel together with the channel pore occlusion.

FJ44 Turbofan Engine Test at NASA Glenn Research Center's Aero-Acoustic Propulsion Laboratory

NASA Technical Reports Server (NTRS)

Lauer, Joel T.; McAllister, Joseph; Loew, Raymond A.; Sutliff, Daniel L.; Harley, Thomas C.

2009-01-01

A Williams International FJ44-3A 3000-lb thrust class turbofan engine was tested in the NASA Glenn Research Center s Aero-Acoustic Propulsion Laboratory. This report presents the test set-up and documents the test conditions. Farfield directivity, in-duct unsteady pressures, duct mode data, and phased-array data were taken and are reported separately.

Evaluation of the aero-optical properties of the SOFIA cavity by means of computional fluid dynamics and a super fast diagnostic camera

NASA Astrophysics Data System (ADS)

Engfer, Christian; Pfüller, Enrico; Wiedemann, Manuel; Wolf, Jürgen; Lutz, Thorsten; Krämer, Ewald; Röser, Hans-Peter

2012-09-01

The Stratospheric Observatory for Infrared Astronomy (SOFIA) is a 2.5 m reflecting telescope housed in an open cavity on board of a Boeing 747SP. During observations, the cavity is exposed to transonic flow conditions. The oncoming boundary layer evolves into a free shear layer being responsible for optical aberrations and for aerodynamic and aeroacoustic disturbances within the cavity. While the aero-acoustical excitation of an airborne telescope can be minimized by using passive flow control devices, the aero-optical properties of the flow are difficult to improve. Hence it is important to know how much the image seen through the SOFIA telescope is perturbed by so called seeing effects. Prior to the SOFIA science fights Computational Fluid Dynamics (CFD) simulations using URANS and DES methods were carried out to determine the flow field within and above the cavity and hence in the optical path in order to provide an assessment of the aero-optical properties under baseline conditions. In addition and for validation purposes, out of focus images have been taken during flight with a Super Fast Diagnostic Camera (SFDC). Depending on the binning factor and the sub-array size, the SFDC is able to take and to read out images at very high frame rates. The paper explains the numerical approach based on CFD to evaluate the aero-optical properties of SOFIA. The CFD data is then compared to the high speed images taken by the SFDC during flight.

Radiative Forcing of the Direct Aerosol Effect from AeroCom Phase II Simulations

NASA Technical Reports Server (NTRS)

Myhre, G.; Samset, B. H.; Schulz, M.; Balkanski, Y.; Bauer, S.; Berntsen, T. K.; Bian, H.; Bellouin, N.; Chin, M.; Diehl, T.;

77 FR 24360 - Airworthiness Directives; Sicma Aero Seat Passenger Seat Assemblies, Installed on, But Not...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-24

... accordance with paragraphs 2/A through D2. of the Accomplishment Instructions of Sicma Aero Seat Service... flight, replace the affected spreader, in accordance with paragraphs 2/A through D2. of the... (modifying to ``Amendment B'' standard), in accordance with paragraphs 2/A through D2. of the Accomplishment...

Frequency of common polymorphisms in Caveolin 1 (CAV1 ) gene in adults with high serum triglycerides from Colombian Caribbean Coast

PubMed Central

Ruiz-Diaz, Maria Stephany; Gomez-Camargo, Doris Esther; Gomez-Alegria, Claudio Jaime

2017-01-01

Abstract Background: Caveolin 1 gene (CAV1) has been associated with insulin resistance, metabolic syndrome and hypertension in humans. Also, it has been related to high serum triglycerides in rodents, however there is little evidence of this relation in humans. Aim: To describe frequencies of common variations in CAV1 in adults with high serum triglycerides. Methods: A case-control study was carried out with adults from Colombian Caribbean Coast. A whole blood sample was employed to measure serum concentrations of triglycerides, glucose, total cholesterol and HDLc. Six common Single Nucleotide Polymorphism (SNP) in CAV1 were genotyped (rs926198, rs3779512, rs10270569, rs11773845, rs7804372 and rs1049337). Allelic and genotypic frequencies were determined by direct count and Hardy-Weinberg Equilibrium (HWE) was assessed. Case and control groups were compared with null-hypothesis tests. Results: A total of 220 cases and 220 controls were included. For rs3779512 an excess in homozygotes frequency was found within case group (40.4% (GG), 41.3% (GT) and 18.1% (TT); Fis=0.13, p=0.03). Another homozygotes excess among case group was found in rs7804372 (59.5% (TT), 32.3% (TA) and 8.2% (AA); Fis= 0.12, p= 0.04). In rs1049337, cases also showed an excess in homozygotes frequency (52.7% (CC), 35.0% (CT) and 12.3% (TT); Fis= 0.16, p= 0.01). Finally, for rs1049337 there were differences in genotype distribution between case and control groups (p <0.05). Conclusion: An increased frequency of homozygote genotypes was found in subjects with high serum triglycerides. These findings suggest that minor alleles for SNPs rs3779512, rs7804372 and rs1049337 might be associated to higher risk of hypertriglyceridemia. PMID:29662258

An AeroCom Assessment of Black Carbon in Arctic Snow and Sea Ice

NASA Technical Reports Server (NTRS)

Jiao, C.; Flanner, M. G.; Balkanski, Y.; Bauer, S. E.; Bellouin, N.; Bernsten, T. K.; Bian, H.; Carslaw, K. S.; Chin, M.; DeLuca, N.;

An AeroCom assessment of black carbon in Arctic snow and sea ice

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

Jiao, C.; Flanner, M. G.; Balkanski, Y.

2014-01-01

Though many global aerosols models prognose surface deposition, only a few models have been used to directly simulate the radiative effect from black carbon (BC) deposition to snow and sea ice. In this paper, we apply aerosol deposition fields from 25 models contributing to two phases of the Aerosol Comparisons between Observations and Models (AeroCom) project to simulate and evaluate within-snow BC concentrations and radiative effect in the Arctic. We accomplish this by driving the offline land and sea ice components of the Community Earth System Model with different deposition fields and meteorological conditions from 2004 to 2009, during whichmore » an extensive field campaign of BC measurements in Arctic snow occurred. We find that models generally underestimate BC concentrations in snow in northern Russia and Norway, while overestimating BC amounts elsewhere in the Arctic. Although simulated BC distributions in snow are poorly correlated with measurements, mean values are reasonable. The multi-model mean (range) bias in BC concentrations, sampled over the same grid cells, snow depths, and months of measurements, are -4.4 (-13.2 to +10.7) ng g -1 for an earlier phase of AeroCom models (phase I), and +4.1 (-13.0 to +21.4) ng g -1 for a more recent phase of AeroCom models (phase II), compared to the observational mean of 19.2 ng g -1. Factors determining model BC concentrations in Arctic snow include Arctic BC emissions, transport of extra-Arctic aerosols, precipitation, deposition efficiency of aerosols within the Arctic, and meltwater removal of particles in snow. Sensitivity studies show that the model–measurement evaluation is only weakly affected by meltwater scavenging efficiency because most measurements were conducted in non-melting snow. The Arctic (60–90° N) atmospheric residence time for BC in phase II models ranges from 3.7 to 23.2 days, implying large inter-model variation in local BC deposition efficiency. Combined with the fact that most

An Airbreathing Launch Vehicle Design with Turbine-Based Low-Speed Propulsion and Dual Mode Scramjet High-Speed Propulsion

NASA Technical Reports Server (NTRS)

Moses, P. L.; Bouchard, K. A.; Vause, R. F.; Pinckney, S. Z.; Ferlemann, S. M.; Leonard, C. P.; Taylor, L. W., III; Robinson, J. S.; Martin, J. G.; Petley, D. H.

1999-01-01

Airbreathing launch vehicles continue to be a subject of great interest in the space access community. In particular, horizontal takeoff and horizontal landing vehicles are attractive with their airplane-like benefits and flexibility for future space launch requirements. The most promising of these concepts involve airframe integrated propulsion systems, in which the external undersurface of the vehicle forms part of the propulsion flowpath. Combining of airframe and engine functions in this manner involves all of the design disciplines interacting at once. Design and optimization of these configurations is a most difficult activity, requiring a multi-discipline process to analytically resolve the numerous interactions among the design variables. This paper describes the design and optimization of one configuration in this vehicle class, a lifting body with turbine-based low-speed propulsion. The integration of propulsion and airframe, both from an aero-propulsive and mechanical perspective are addressed. This paper primarily focuses on the design details of the preferred configuration and the analyses performed to assess its performance. The integration of both low-speed and high-speed propulsion is covered. Structural and mechanical designs are described along with materials and technologies used. Propellant and systems packaging are shown and the mission-sized vehicle weights are disclosed.

76 FR 7694 - Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Model PIAGGIO P-180 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-11

... Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Model PIAGGIO P-180 Airplanes AGENCY: Federal Aviation... Piaggio service bulletin number specified in the Alternative Methods of Compliance (AMOCs) section is..., except Federal holidays. The AD docket contains this AD, the regulatory evaluation, any comments received...

Design Optimization of Space Launch Vehicles Using a Genetic Algorithm

DTIC Science & Technology

2007-06-01

function until no improvement in the objective function could be made. The search space is modeled in a geometric form such as a polyhedron . The simplex... database . AeroDesign assumes that there are no boundary layers and that no separation occurs. AeroDesign can analyze either a cone or ogive shape

75 FR 6860 - Airworthiness Directives; International Aero Engines AG (IAE) V2500-A1, V2522-A5, V2524-A5, V2525...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-12

... Airworthiness Directives; International Aero Engines AG (IAE) V2500-A1, V2522-A5, V2524-A5, V2525-D5, V2527-A5, V2527E-A5, V2527M-A5, V2528-D5, V2530-A5, and V2533-A5 Turbofan Engines AGENCY: Federal Aviation... airworthiness directive (AD) for all International Aero Engines AG (IAE) V2500-A1, V2525-D5 and V2528-D5...

Development Of Metallic Thermal Protection System For The Expert Re-Entry Vehicle: Design Verification

NASA Astrophysics Data System (ADS)

Fatemi, Javad

2011-05-01

The thermal protection system of the EXPERT re-entry vehicle is subjected to accelerations, vibrations, acoustic and shock loads during launch and aero-heating loads and aerodynamic forces during re-entry. To fully understand the structural and thermomechanical performances of the TPS, heat transfer analysis, thermal stress analysis, and thermal buckling analysis must be performed. This requires complex three-dimensional thermal and structural models of the entire TPS including the insulation and sensors. Finite element (FE) methods are employed to assess the thermal and structural response of the TPS to the mechanical and aerothermal loads. The FE analyses results are used for the design verification and design improvement of the EXPERT thermal protection system.

The Modular Aero-Propulsion System Simulation (MAPSS) Users' Guide

NASA Technical Reports Server (NTRS)

Parker, Khary I.; Melcher, Kevin J.

2004-01-01

The Modular Aero-Propulsion System Simulation is a flexible turbofan engine simulation environment that provides the user a platform to develop advanced control algorithms. It is capable of testing the performance of control designs on a validated and verified generic engine model. In addition, it is able to generate state-space linear models of the engine model to aid in controller design. The engine model used in MAPSS is a generic high-pressure ratio, dual-spool, lowbypass, military-type, variable cycle turbofan engine with a digital controller. MAPSS is controlled by a graphical user interface (GUI) and this guide explains how to use it to take advantage of the capabilities of MAPSS.

ACTS Aeronautical Terminal Experiment (AERO-X)

NASA Technical Reports Server (NTRS)

1995-01-01

During the summer of 1994, the performance of an experimental mobile satellite communication system was demonstrated. Using the Advanced Communications Technology Satellite (ACTS) and the ACTS Mobile Terminal (AMT), the system demonstrated an active Monolithic Microwave Integrated Circuit (MMIC) phased-array antenna system. The antenna system was installed onboard one of NASA Lewis Research Center's research aircraft, a Learjet Model 25. It proved the viability of in-flight satellite communications services via small, flush, mountable electronic phased-array antennas. The overall system setup for the ACTS Aeronautical Terminal Experiment (AERO-X) is illustrated. The Link Evaluation Terminal (LET) at Lewis in Cleveland, Ohio, interfaced with fixed-AMT equipment, providing a seamless connection with the Public Service Telephone Network. As the Learjet was flown over several major cities across the U.S., this demonstration system allowed passengers onboard to make telephone calls as if they were using a cellular system. ACTS was operated in its microwave switch matrix mode with a spot beam for the Learjet and another spot beam dedicated to the LET.

Synergistic mutual potentiation of antifungal activity of Zuccagnia punctata Cav. and Larrea nitida Cav. extracts in clinical isolates of Candida albicans and Candida glabrata.

PubMed

Butassi, Estefanía; Svetaz, Laura A; Ivancovich, Juan J; Feresin, Gabriela E; Tapia, Alejandro; Zacchino, Susana A

2015-06-01

Zuccagnia punctata Cav. (Fabaceae) and Larrea nitida Cav. (Zygophyllaceae) are indistinctly or jointly used in traditional medicine for the treatment of fungal-related infections. Although their dichloromethane (DCM) extract have demonstrated moderate antifungal activities when tested on their own, antifungal properties of combinations of both plants have not been assessed previously. The aim of this study was to establish with statistical rigor whether Z. punctata (ZpE) and L. nitida DCM extract (LnE) interact synergistically against the clinically important fungi Candida albicans and Candida glabrata and to characterize the most synergistic combinations. For synergism assessment, the statistical-based Boik's design was applied. Eight ZpE-LnE fixed-ratio mixtures were prepared from four different months of 1 year and tested against Candida strains. Lϕ (Loewe index) of each mixture at different fractions affected (ϕ) allowed for the finding of the most synergistic combinations, which were characterized by HPLC fingerprint and by the quantitation of the selected marker compounds. Lϕ and confidence intervals were determined in vitro with the MixLow method, once the estimated parameters from the dose-response curves of independent extracts and mixtures, were obtained. Markers (four flavonoids for ZpE and three lignans for LnE) were quantified in each extract and their combinations, with a valid HPLC-UV method. The 3D-HPLC profiles of the most synergistic mixtures were obtained by HPLC-DAD. Three over four IC50ZpE/IC50LnE fixed-ratio mixtures displayed synergistic interactions at effect levels ϕ > 0.5 against C. albicans. The dosis of the most synergistic (Lϕ = 0.62) mixture was 65.96 µg/ml (ZpE = 28%; LnE = 72%) containing 8 and 36% of flavonoids and lignans respectively. On the other hand, one over four IC50ZpE/IC50LnE mixtures displays synergistic interactions at ϕ > 0.5 against C. glabrata. The dosis of the most synergistic (Lϕ = 0.67) mixture was 168

CACNA1H missense mutations associated with amyotrophic lateral sclerosis alter Cav3.2 T-type calcium channel activity and reticular thalamic neuron firing.

PubMed

Rzhepetskyy, Yuriy; Lazniewska, Joanna; Blesneac, Iulia; Pamphlett, Roger; Weiss, Norbert

2016-11-01

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. In a recent study by Steinberg and colleagues, 2 recessive missense mutations were identified in the Cav3.2 T-type calcium channel gene (CACNA1H), in a family with an affected proband (early onset, long duration ALS) and 2 unaffected parents. We have introduced and functionally characterized these mutations using transiently expressed human Cav3.2 channels in tsA-201 cells. Both of these mutations produced mild but significant changes on T-type channel activity that are consistent with a loss of channel function. Computer modeling in thalamic reticular neurons suggested that these mutations result in decreased neuronal excitability of thalamic structures. Taken together, these findings implicate CACNA1H as a susceptibility gene in amyotrophic lateral sclerosis.

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

Zhang, Yue J.; Malikopoulos, Andreas; Cassandras, Christos G.

We address the problem of coordinating online a continuous flow of connected and automated vehicles (CAVs) crossing two adjacent intersections in an urban area. We present a decentralized optimal control framework whose solution yields for each vehicle the optimal acceleration/deceleration at any time in the sense of minimizing fuel consumption. The solu- tion, when it exists, allows the vehicles to cross the intersections without the use of traffic lights, without creating congestion on the connecting road, and under the hard safety constraint of collision avoidance. The effectiveness of the proposed solution is validated through simulation considering two intersections located inmore » downtown Boston, and it is shown that coordination of CAVs can reduce significantly both fuel consumption and travel time.« less

Wind tunnel validation of AeroDyn within LIFES50+ project: imposed Surge and Pitch tests

NASA Astrophysics Data System (ADS)

Bayati, I.; Belloli, M.; Bernini, L.; Zasso, A.

2016-09-01

This paper presents the first set of results of the steady and unsteady wind tunnel tests, performed at Politecnico di Milano wind tunnel, on a 1/75 rigid scale model of the DTU 10 MW wind turbine, within the LIFES50+ project. The aim of these tests is the validation of the open source code AeroDyn developed at NREL. Numerical and experimental steady results are compared in terms of thrust and torque coefficients, showing good agreement, as well as for unsteady measurements gathered with a 2 degree-of-freedom test rig, capable of imposing the displacements at the base of the model, and providing the surge and pitch motion of the floating offshore wind turbine (FOWT) scale model. The measurements of the unsteady test configuration are compared with AeroDyn/Dynin module results, implementing the generalized dynamic wake (GDW) model. Numerical and experimental comparison showed similar behaviours in terms of non linear hysteresis, however some discrepancies are herein reported and need further data analysis and interpretations about the aerodynamic integral quantities, with a special attention to the physics of the unsteady phenomenon.

Relative Contributions of Regional and Sector Emissions to the Radiative Forcing of Aerosol-Radiation and Aerosol-Cloud Interactions Based on the AeroCOM Phase III/HTAP2 Experiment

NASA Astrophysics Data System (ADS)

Takemura, T.; Chin, M.

2014-12-01

It is important to understand relative contributions of each regional and sector emission of aerosols and their precursor gases to the regional and global mean radiative forcing of aerosol-radiation and aerosol-cloud interactions. This is because it is useful for international cooperation on controls of air pollution and anthropogenic climate change along most suitable reduction path of their emissions from each region and sector. The Task Force on Hemispheric Transport of Air Pollution (TF HTAP) under the United Nations researches the intercontinental transport of air pollutants including aerosols with strong support of the Aerosol Comparisons between Observations and Models (AeroCOM). The ongoing AeroCOM Phase III/HTAP2 experiment assesses relative contributions of regional and sector sources of aerosols and their precursor gases to the air quality using global aerosol transport models with latest emission inventories. In this study, the extended analyses on the relative contributions of each regional and sector emission to the radiative forcing of aerosol-radiation and aerosol-cloud interactions are done from the AeroCOM Phase III/HTAP2 experiment. Simulated results from MIROC-SPRINTARS and other some global aerosol models participating in the the AeroCOM Phase III/HTAP2 experiment are assessed. Acknowledgements: This study is based on the AeroCOM Phase III/HTAP2 experiment and partly supported by the Environment Research and Technology Development Fund (S-12-3) of the Ministry of the Environment, Japan.

75 FR 43101 - Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Model PIAGGIO P-180 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-23

...) Code 79: Engine Oil. Reason (e) The mandatory continuing airworthiness information (MCAI) states: A... fuel heater caused a fuel leakage in the engine nacelle; investigation revealed that the damage to the fuel heater was due to chafing with an oil cooling system hose. PIAGGIO AERO INDUSTIRES (PAI) issued...

75 FR 22512 - Airworthiness Directives; Piaggio Aero Industries S.p.A. Model PIAGGIO P-180 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-29

... Airworthiness Directives; Piaggio Aero Industries S.p.A. Model PIAGGIO P-180 Airplanes AGENCY: Federal Aviation... presence of potential ignition sources such as electrical equipment and connectors. As a consequence, this..., agree with their substance. But we might have found it necessary to use different words from those in...

A Co-modeling Method Based on Component Features for Mechatronic Devices in Aero-engines

NASA Astrophysics Data System (ADS)

Wang, Bin; Zhao, Haocen; Ye, Zhifeng

2017-08-01

Data-fused and user-friendly design of aero-engine accessories is required because of their structural complexity and stringent reliability. This paper gives an overview of a typical aero-engine control system and the development process of key mechatronic devices used. Several essential aspects of modeling and simulation in the process are investigated. Considering the limitations of a single theoretic model, feature-based co-modeling methodology is suggested to satisfy the design requirements and compensate for diversity of component sub-models for these devices. As an example, a stepper motor controlled Fuel Metering Unit (FMU) is modeled in view of the component physical features using two different software tools. An interface is suggested to integrate the single discipline models into the synthesized one. Performance simulation of this device using the co-model and parameter optimization for its key components are discussed. Comparison between delivery testing and the simulation shows that the co-model for the FMU has a high accuracy and the absolute superiority over a single model. Together with its compatible interface with the engine mathematical model, the feature-based co-modeling methodology is proven to be an effective technical measure in the development process of the device.

Modulation of CaV1.2 calcium channel by neuropeptide W regulates vascular myogenic tone via G protein-coupled receptor 7.

PubMed

Ji, Li; Zhu, Huayuan; Chen, Hong; Fan, Wenyong; Chen, Junjie; Chen, Jing; Zhu, Guoqing; Wang, Juejin

2015-12-01

Neuropeptide W (NPW), an endogenous ligand for the G protein-coupled receptor 7 (GPR7), was first found to make important roles in central nerve system. In periphery, NPW was also present and regulated intracellular calcium homeostasis by L-type calcium channels. This study was designed to discover the effects of NPW-GPR7 on the function of CaV1.2 calcium channels in the vascular smooth muscle cells (VSMCs) and vasotone of arterial vessels. By whole-cell patch clamp, we studied the effects of NPW-23, the active form of NPW, on the CaV1.2 channels in the heterologously transfected human embryonic kidney 293 cells and VSMCs isolated from rat. Living system was used to explore the physiological function of NPW-23 in arterial myogenic tone. To investigate the pathological relevance, NPW mRNA level of mesenteric arteries was measured in the hypertensive and normotensive rats. NPW's receptor GPR7 was coexpressed with CaV1.2 channels in arterial smooth muscle. NPW-23 increased the ICa,L in transfected human embryonic kidney 293 cells and VSMCs via GPR7, which could be abrogated by phospholipase C (PLC)/protein kinase C (PKC) inhibitors, not protein kinase A or protein kinase G inhibitor. After NPW-23 application, the expression of pan phospho-PKC was increased; moreover, intracellular diacylglycerol level, the second messenger catalyzed by PLC, was increased 1.5-2-fold. Application with NPW-23 increased pressure-induced vasotone of the rat mesenteric arteries. Importantly, the expression of NPW was decreased in the hypertensive rats. NPW-23 regulates ICa,L via GPR7, which is mediated by PLC/PKC signaling, and such a mechanism plays a role in modulating vascular myogenic tone, which may involve in the development of vascular hypertension.

Numerical prediction of the spatial and temporal characteristics of the aero-optical disturbance produced by a helicopter in hover

NASA Astrophysics Data System (ADS)

Kelly, Ryan T.

Aero-optical disturbances produced from turbulent compressible flow-fields can seriously degrade the performance of an optical signal. At compressible flight speeds these disturbances stem from the density variations present in turbulent boundary layers and free shear layers; however helicopters typically operate at incompressible speeds, which nearly eliminates the aberrating effect of these flows. For helicopter platforms the sources of aberration originate from the high subsonic flow-field near the rotor blade tips in the form of rotor-tip vortices and from the high temperatures of the engine effluence. During hover the shed rotor-tip vortices and engine effluence convect with the rotor wake encircling the airframe and subsequently a helicopter mounted optical system. The aero-optical effects of the wake beneath a hovering helicopter were analyzed using a combination of Unsteady RANS (URANS) and Large-Eddy Simulations (LES). The spatial and temporal characteristics of the numerical optical wavefronts were compared to full-scale aero-optic experimental measurements. The results indicate that the turbulence of the rotor-tip vortices contributes to the higher order aberrations measured experimentally and that the thermal exhaust plumes effectively limit the optical field-of-regard to forward- and side-looking beam directions. This information along with the computed optical aberrations of the wake can be used to guide the development of adaptive-optic systems or other beam-control approaches.

Small wind turbine performance evaluation using field test data and a coupled aero-electro-mechanical model

NASA Astrophysics Data System (ADS)

Wallace, Brian D.

A series of field tests and theoretical analyses were performed on various wind turbine rotor designs at two Penn State residential-scale wind-electric facilities. This work involved the prediction and experimental measurement of the electrical and aerodynamic performance of three wind turbines; a 3 kW rated Whisper 175, 2.4 kW rated Skystream 3.7, and the Penn State designed Carolus wind turbine. Both the Skystream and Whisper 175 wind turbines are OEM blades which were originally installed at the facilities. The Carolus rotor is a carbon-fiber composite 2-bladed machine, designed and assembled at Penn State, with the intent of replacing the Whisper 175 rotor at the off-grid system. Rotor aerodynamic performance is modeled using WT_Perf, a National Renewable Energy Laboratory developed Blade Element Momentum theory based performance prediction code. Steady-state power curves are predicted by coupling experimentally determined electrical characteristics with the aerodynamic performance of the rotor simulated with WT_Perf. A dynamometer test stand is used to establish the electromechanical efficiencies of the wind-electric system generator. Through the coupling of WT_Perf and dynamometer test results, an aero-electro-mechanical analysis procedure is developed and provides accurate predictions of wind system performance. The analysis of three different wind turbines gives a comprehensive assessment of the capability of the field test facilities and the accuracy of aero-electro-mechanical analysis procedures. Results from this study show that the Carolus and Whisper 175 rotors are running at higher tip-speed ratios than are optimum for power production. The aero-electro-mechanical analysis predicted the high operating tip-speed ratios of the rotors and was accurate at predicting output power for the systems. It is shown that the wind turbines operate at high tip-speeds because of a miss-match between the aerodynamic drive torque and the operating torque of the wind

Processing of Advanced Ceramics Which Have Potential for Use in Gas Turbine Aero Engines

DTIC Science & Technology

1989-02-01

reaons . Details on the availability of these publications may be obtained from: Graphics Section, National Research Council Canada, National...have been produced by hot isostatic pressing (HIP’ing) have good potential to be used as hot section components in gas turbine aero engines. This...Alumina, for example, maintains good corrosion resistance, good stiffness, and good strength at high temperatures, but exhibits very poor thermal shock

75 FR 63062 - Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Model PIAGGIO P-180 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-14

... Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Model PIAGGIO P-180 Airplanes AGENCY: Federal Aviation..., PAI introduced a new Hose Assembly (P/N 80-337284- 001), which allows better clearances and removes... aeroplanes with the old P/N installed only and giving instructions for the replacement with the new Hose...

75 FR 7409 - Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Model PIAGGIO P-180 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-19

... INDUSTRIES S.p.A Model PIAGGIO P-180 Airplanes AGENCY: Federal Aviation Administration (FAA), Department of.... As a consequence, this new Airworthiness Directive (AD) requires a functional check of main and stand... AERO INDUSTRIES S.p.A. has issued Service Bulletin (Mandatory) N.: 80-0278, dated July 15, 2009. The...

76 FR 67243 - In the Matter of Accesspoint Corp., Aero Performance Products, Inc., Apex Resources Group, Inc...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-31

... Performance Products, Inc., Apex Resources Group, Inc., Aradyme Corp., Bancroft Uranium, Inc., Fightersoft Multimedia Corp., Fortress Financial Group, Inc., and Global Aircraft Solutions, Inc.; Order of Suspension of... securities of Aero Performance Products, Inc. because it has not filed any periodic reports since the period...

Trajectory optimization study of a lifting body re-entry vehicle for medium to intermediate range applications

NASA Astrophysics Data System (ADS)

Rizvi, S. Tauqeer ul Islam; Linshu, He; ur Rehman, Tawfiq; Rafique, Amer Farhan

2012-11-01

A numerical optimization study of lifting body re-entry vehicles is presented for nominal as well as shallow entry conditions for Medium and Intermediate Range applications. Due to the stringent requirement of a high degree of accuracy for conventional vehicles, lifting re-entry can be used to attain the impact at the desired terminal flight path angle and speed and thus can potentially improve accuracy of the re-entry vehicle. The re-entry of a medium range and intermediate range vehicles is characterized by very high negative flight path angle and low re-entry speed as compared to a maneuverable re-entry vehicle or a common aero vehicle intended for an intercontinental range. Highly negative flight path angles at the re-entry impose high dynamic pressure as well as heat loads on the vehicle. The trajectory studies are carried out to maximize the cross range of the re-entry vehicle while imposing a maximum dynamic pressure constraint of 350 KPa with a 3 MW/m2 heat rate limit. The maximum normal acceleration and the total heat load experienced by the vehicle at the stagnation point during the maneuver have been computed for the vehicle for possible future conceptual design studies. It has been found that cross range capability of up to 35 km can be achieved with a lifting-body design within the heat rate and the dynamic pressure boundary at normal entry conditions. For shallow entry angle of -20 degree and intermediate ranges a cross range capability of up to 250 km can be attained for a lifting body design with less than 10 percent loss in overall range. The normal acceleration also remains within limits. The lifting-body results have also been compared with wing-body results at shallow entry condition. An hp-adaptive pseudo-spectral method has been used for constrained trajectory optimization.

CONSIDERATIONS ON ANATOMY AND PHYSIOLOGY OF LYMPH VESSELS OF UPPER AERO DIGESTIVE ORGANS AND CERVICAL SATELLITE LYMPH NODE GROUP.

PubMed

Ciupilan, Corina; Stan, C I

2016-01-01

The almost constant local regional development of the cancers of upper aero digestive organs requires the same special attention to cervical lymph node metastases, as well as to the primary neoplastic burning point. The surgical therapy alone or associated has a mutilating, damaging character, resulting in loss of an organ and function, most of the times with social implications, involving physical distortions with aesthetic consequences, which make the reintegration of the individual into society questionable. The problem of cervical lymph node metastases is vast and complex, reason why we approached several anatomical and physiological aspects of lymph vessels of the aero digestive organs. Among the available elements during treatment, the headquarters of the tumour, its histologic degree, and its infiltrative nature, each of them significantly influences the possibility of developing metastases.

76 FR 72235 - Abviva, Inc., ACTIS Global Ventures, Inc., aeroTelesis, Inc., Amwest Insurance Group, Inc., and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-22

... SECURITIES AND EXCHANGE COMMISSION [File No. 500-1] Abviva, Inc., ACTIS Global Ventures, Inc., aeroTelesis, Inc., Amwest Insurance Group, Inc., and Auto Underwriters of America, Inc.; Order of... concerning the securities of Auto Underwriters of America, Inc. because it has not filed any periodic reports...

An engineer at AeroVironment's Design Development Center inspects a set of silicon solar cells for p

NASA Technical Reports Server (NTRS)

2000-01-01

An engineer at AeroVironment's Design Development Center in Simi Valley, California, closely inspects a set of silicon solar cells for potential defects. The cells, fabricated by SunPower, Inc., of Sunnyvale, California, are among 64,000 solar cells which have been installed on the Helios Prototype solar-powered aircraft to provide power to its 14 electric motors and operating systems. Developed by AeroVironment under NASA's Environmental Research Aircraft and Sensor Technology (ERAST) project, the Helios Prototype is the forerunner of a planned fleet of slow-flying, long duration, high-altitude aircraft which can perform atmospheric science missions and serve as telecommunications relay platforms in the stratosphere. Target goals set by NASA for the giant 246-foot span flying wing include reaching and sustaining subsonic horizontal flight at 100,000 feet altitude in 2001, and sustained continuous flight for at least four days and nights in 2003 with the aid of a regenerative fuel cell-based energy storage system now in development.

Aerosols at the poles: an AeroCom Phase II multi-model evaluation

DOE PAGES

Sand, Maria; Samset, Bjorn H.; Balkanski, Yves; ...

2017-10-13

Atmospheric aerosols from anthropogenic and natural sources reach the polar regions through long-range transport and affect the local radiation balance. Such transport is, however, poorly constrained in present-day global climate models, and few multi-model evaluations of polar anthropogenic aerosol radiative forcing exist. Here we compare the aerosol optical depth (AOD) at 550 nm from simulations with 16 global aerosol models from the AeroCom Phase II model intercomparison project with available observations at both poles. We show that the annual mean multi-model median is representative of the observations in Arctic, but that the intermodel spread is large. We also document themore » geographical distribution and seasonal cycle of the AOD for the individual aerosol species: black carbon (BC) from fossil fuel and biomass burning, sulfate, organic aerosols (OAs), dust, and sea-salt. For a subset of models that represent nitrate and secondary organic aerosols (SOAs), we document the role of these aerosols at high latitudes. The seasonal dependence of natural and anthropogenic aerosols differs with natural aerosols peaking in winter (sea-salt) and spring (dust), whereas AOD from anthropogenic aerosols peaks in late spring and summer. The models produce a median annual mean AOD of 0.07 in the Arctic (defined here as north of 60° N). The models also predict a noteworthy aerosol transport to the Antarctic (south of 70° S) with a resulting AOD varying between 0.01 and 0.02. The models have estimated the shortwave anthropogenic radiative forcing contributions to the direct aerosol effect (DAE) associated with BC and OA from fossil fuel and biofuel (FF), sulfate, SOAs, nitrate, and biomass burning from BC and OA emissions combined. The Arctic modelled annual mean DAE is slightly negative (-0.12 W m -2), dominated by a positive BC FF DAE in spring and a negative sulfate DAE in summer. The Antarctic DAE is governed by BC FF. We perform sensitivity experiments with one of

Aerosols at the poles: an AeroCom Phase II multi-model evaluation

NASA Astrophysics Data System (ADS)

Sand, Maria; Samset, Bjørn H.; Balkanski, Yves; Bauer, Susanne; Bellouin, Nicolas; Berntsen, Terje K.; Bian, Huisheng; Chin, Mian; Diehl, Thomas; Easter, Richard; Ghan, Steven J.; Iversen, Trond; Kirkevåg, Alf; Lamarque, Jean-François; Lin, Guangxing; Liu, Xiaohong; Luo, Gan; Myhre, Gunnar; van Noije, Twan; Penner, Joyce E.; Schulz, Michael; Seland, Øyvind; Skeie, Ragnhild B.; Stier, Philip; Takemura, Toshihiko; Tsigaridis, Kostas; Yu, Fangqun; Zhang, Kai; Zhang, Hua

2017-10-01

Atmospheric aerosols from anthropogenic and natural sources reach the polar regions through long-range transport and affect the local radiation balance. Such transport is, however, poorly constrained in present-day global climate models, and few multi-model evaluations of polar anthropogenic aerosol radiative forcing exist. Here we compare the aerosol optical depth (AOD) at 550 nm from simulations with 16 global aerosol models from the AeroCom Phase II model intercomparison project with available observations at both poles. We show that the annual mean multi-model median is representative of the observations in Arctic, but that the intermodel spread is large. We also document the geographical distribution and seasonal cycle of the AOD for the individual aerosol species: black carbon (BC) from fossil fuel and biomass burning, sulfate, organic aerosols (OAs), dust, and sea-salt. For a subset of models that represent nitrate and secondary organic aerosols (SOAs), we document the role of these aerosols at high latitudes.The seasonal dependence of natural and anthropogenic aerosols differs with natural aerosols peaking in winter (sea-salt) and spring (dust), whereas AOD from anthropogenic aerosols peaks in late spring and summer. The models produce a median annual mean AOD of 0.07 in the Arctic (defined here as north of 60° N). The models also predict a noteworthy aerosol transport to the Antarctic (south of 70° S) with a resulting AOD varying between 0.01 and 0.02. The models have estimated the shortwave anthropogenic radiative forcing contributions to the direct aerosol effect (DAE) associated with BC and OA from fossil fuel and biofuel (FF), sulfate, SOAs, nitrate, and biomass burning from BC and OA emissions combined. The Arctic modelled annual mean DAE is slightly negative (-0.12 W m-2), dominated by a positive BC FF DAE in spring and a negative sulfate DAE in summer. The Antarctic DAE is governed by BC FF. We perform sensitivity experiments with one of the Aero

Aerosols at the poles: an AeroCom Phase II multi-model evaluation

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

Sand, Maria; Samset, Bjorn H.; Balkanski, Yves

Atmospheric aerosols from anthropogenic and natural sources reach the polar regions through long-range transport and affect the local radiation balance. Such transport is, however, poorly constrained in present-day global climate models, and few multi-model evaluations of polar anthropogenic aerosol radiative forcing exist. Here we compare the aerosol optical depth (AOD) at 550 nm from simulations with 16 global aerosol models from the AeroCom Phase II model intercomparison project with available observations at both poles. We show that the annual mean multi-model median is representative of the observations in Arctic, but that the intermodel spread is large. We also document themore » geographical distribution and seasonal cycle of the AOD for the individual aerosol species: black carbon (BC) from fossil fuel and biomass burning, sulfate, organic aerosols (OAs), dust, and sea-salt. For a subset of models that represent nitrate and secondary organic aerosols (SOAs), we document the role of these aerosols at high latitudes. The seasonal dependence of natural and anthropogenic aerosols differs with natural aerosols peaking in winter (sea-salt) and spring (dust), whereas AOD from anthropogenic aerosols peaks in late spring and summer. The models produce a median annual mean AOD of 0.07 in the Arctic (defined here as north of 60° N). The models also predict a noteworthy aerosol transport to the Antarctic (south of 70° S) with a resulting AOD varying between 0.01 and 0.02. The models have estimated the shortwave anthropogenic radiative forcing contributions to the direct aerosol effect (DAE) associated with BC and OA from fossil fuel and biofuel (FF), sulfate, SOAs, nitrate, and biomass burning from BC and OA emissions combined. The Arctic modelled annual mean DAE is slightly negative (-0.12 W m -2), dominated by a positive BC FF DAE in spring and a negative sulfate DAE in summer. The Antarctic DAE is governed by BC FF. We perform sensitivity experiments with one of

Dynamic modeling and vibration characteristics analysis of the aero-engine dual-rotor system with Fan blade out

NASA Astrophysics Data System (ADS)

Yu, Pingchao; Zhang, Dayi; Ma, Yanhong; Hong, Jie

2018-06-01

Fan Blade Out (FBO) from a running rotor of the turbofan engine will not only introduce the sudden unbalance and inertia asymmetry into the rotor, but also apply large impact load and induce rotor-to-stator rubbing on the rotor, which makes the mass, gyroscopic and stiffness matrixes of the dynamic equation become time-varying and highly nonlinear, consequently leads to the system's complicated vibration. The dynamic analysis of the aero-engine rotor system is one essential requirement of the authorities and is vital to the aero-engine's safety. The paper aims at studying the dynamic responses of the complicated dual-rotor systems at instantaneous and windmilling statuses when FBO event occurs. The physical process and mechanical characteristics of the FBO event are described qualitatively, based on which the dynamic modeling for an aero-engine dual-rotor system is carried out considering several excitations caused by FBO. Meanwhile the transient response during the instantaneous status and steady-state response at the windmilling status are obtained. The results reveal that the sudden unbalance can induce impact load to the rotor, and lead to the sharp increase of the vibration amplitude and reaction force. The rub-impact will apply constraint effects on the rotor and restrict the transient vibration amplitude, while the inertia asymmetry has little influence on the transient response. When the rotor with huge unbalance operates at windmilling status, the rub-impact turns to be the main factor determining the rotor's dynamic behavior, and several potential motion states, such as instable dry whip, intermittent rubbing and synchronous full annular rubbing would happen on certain conditions.

OTV Propulsion Issues

NASA Technical Reports Server (NTRS)

1984-01-01

The statistical technology needs of aero-assist maneuvering, propulsion, and usage of cryogenic fluids were presented. Industry panels discussed the servicing of reusable space based vehicles and propulsion-vehicle interation.

Future orbital transfer vehicle technology study. Volume 1: Executive summary

NASA Technical Reports Server (NTRS)

Davis, E. E.

1982-01-01

Reusable space and ground based LO2/LH2 OTV's, both advanced space engines and aero assist capability were compared. The SB OTV provided advantages in life cycle cost, performance and potential for improvement. An all LO2/LH2 OTV fleet was also compared with a fleet of LO2/.H2 OTV's and electric OTV's. The normal growth technology electric OTV used silicon cells with heavy shielding and argon ion thrusters. In this case, the LO2/LH2 OTV fleet provided a 23% advantage in total transportation cost. An accelerated technology LF2/LH2 OTV provided improvements in performance relative to LO2/.H2 OTV but has higher DDT&E cost which negated its cost effectiveness. The accelerated technology electric vehicle used GaAs cells and annealing but still did not result in the mixed fleet being any cheaper than an all LO2/LH2 OTV fleet. It is concluded that reusable LO2/LH2 OTV's can serve all general purpose cargo roles between LEO and GEO for the forseeable future. The most significant technology for the second generation vehicle would be space debris protection, on orbit propellant storage and transfer and on orbit maintenance capability.

Improvement on Main/backup Controller Switching Device of the Nozzle Throat Area Control System for a Turbofan Aero Engine

NASA Astrophysics Data System (ADS)

Li, Jie; Duan, Minghu; Yan, Maode; Li, Gang; Li, Xiaohui

2014-06-01

A full authority digital electronic controller (FADEC) equipped with a full authority hydro-mechanical backup controller (FAHMBC) is adopted as the nozzle throat area control system (NTACS) of a turbofan aero engine. In order to ensure the switching reliability of the main/backup controller, the nozzle throat area control switching valve was improved from three-way convex desktop slide valve to six-way convex desktop slide valve. Simulation results show that, if malfunctions of FAEDC occur and abnormal signals are outputted from FADEC, NTACS will be seriously influenced by the main/backup controller switching in several working states, while NTACS will not be influenced by using the improved nozzle throat area control switching valve, thus the controller switching process will become safer and smoother and the working reliability of this turbofan aero engine is improved by the controller switching device improvement.

Development of methodologies for the estimation of thermal properties associated with aerospace vehicles

NASA Technical Reports Server (NTRS)

Scott, Elaine P.

1993-01-01

Thermal stress analyses are an important aspect in the development of aerospace vehicles such as the National Aero-Space Plane (NASP) and the High-Speed Civil Transport (HSCT) at NASA-LaRC. These analyses require knowledge of the temperature within the structures which consequently necessitates the need for thermal property data. The initial goal of this research effort was to develop a methodology for the estimation of thermal properties of aerospace structural materials at room temperature and to develop a procedure to optimize the estimation process. The estimation procedure was implemented utilizing a general purpose finite element code. In addition, an optimization procedure was developed and implemented to determine critical experimental parameters to optimize the estimation procedure. Finally, preliminary experiments were conducted at the Aircraft Structures Branch (ASB) laboratory.

Development of methodologies for the estimation of thermal properties associated with aerospace vehicles

NASA Astrophysics Data System (ADS)

Scott, Elaine P.

1993-12-01

Thermal stress analyses are an important aspect in the development of aerospace vehicles such as the National Aero-Space Plane (NASP) and the High-Speed Civil Transport (HSCT) at NASA-LaRC. These analyses require knowledge of the temperature within the structures which consequently necessitates the need for thermal property data. The initial goal of this research effort was to develop a methodology for the estimation of thermal properties of aerospace structural materials at room temperature and to develop a procedure to optimize the estimation process. The estimation procedure was implemented utilizing a general purpose finite element code. In addition, an optimization procedure was developed and implemented to determine critical experimental parameters to optimize the estimation procedure. Finally, preliminary experiments were conducted at the Aircraft Structures Branch (ASB) laboratory.

Capability Portfolio Analysis Tool (CPAT) Verification and Validation Report

DTIC Science & Technology

2013-01-01

BFSB Battlefield Surveillance Brigade BFV Bradley Fighting Vehicle BMOD Bradley Modernization C2 (H) Command and Control (HBCT) C2 (S...Fire Infantry Fighting Vehicle (IFV); Fire Integrated Support Team (FIST); Engineer (Eng); Cavalry (CAV) BFV FOV CDD Block II - 16 Apr 2010 GCV FOV

Comparison of phenotypic methods and matrix-assisted laser desorption ionisation time-of-flight mass spectrometry for the identification of aero-tolerant Actinomyces spp. isolated from soft-tissue infections.

PubMed

Ng, L S Y; Sim, J H C; Eng, L C; Menon, S; Tan, T Y

2012-08-01

Aero-tolerant Actinomyces spp. are an under-recognised cause of cutaneous infections, in part because identification using conventional phenotypic methods is difficult and may be inaccurate. Matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS) is a promising new technique for bacterial identification, but with limited data on the identification of aero-tolerant Actinomyces spp. This study evaluated the accuracy of a phenotypic biochemical kit, MALDI-TOF MS and genotypic identification methods for the identification of this problematic group of organisms. Thirty aero-tolerant Actinomyces spp. were isolated from soft-tissue infections over a 2-year period. Species identification was performed by 16 s rRNA sequencing and genotypic results were compared with results obtained by API Coryne and MALDI-TOF MS. There was poor agreement between API Coryne and genotypic identification, with only 33% of isolates correctly identified to the species level. MALDI-TOF MS correctly identified 97% of isolates to the species level, with 33% of identifications achieved with high confidence scores. MALDI-TOF MS is a promising new tool for the identification of aero-tolerant Actinomyces spp., but improvement of the database is required in order to increase the confidence level of identification.

Design, manufacturing and characterization of aero-elastically scaled wind turbine blades for testing active and passive load alleviation techniques within a ABL wind tunnel

NASA Astrophysics Data System (ADS)

Campagnolo, Filippo; Bottasso, Carlo L.; Bettini, Paolo

2014-06-01

In the research described in this paper, a scaled wind turbine model featuring individual pitch control (IPC) capabilities, and equipped with aero-elastically scaled blades featuring passive load reduction capabilities (bend-twist coupling, BTC), was constructed to investigate, by means of wind tunnel testing, the load alleviation potential of BTC and its synergy with active load reduction techniques. The paper mainly focus on the design of the aero-elastic blades and their dynamic and static structural characterization. The experimental results highlight that manufactured blades show desired bend-twist coupling behavior and are a first milestone toward their testing in the wind tunnel.

Telmisartan regresses left ventricular hypertrophy in caveolin-1 deficient mice

PubMed Central

Kreiger, Marta H; Di Lorenzo, Annarita; Teutsch, Christine; Kauser, Katalin; Sessa, William C.

2011-01-01

The role of angiotensin II (Ang II) in promoting cardiac hypertrophy is well known, however the role of the Ang II in a spontaneous model of hypertrophy in mice lacking the protein caveolin-1 (Cav- KO) has not been explored. In this study, WT and Cav-1 KO mice were treated with angiotensin receptor blocker (ARB), telmisartan, and cardiac function assessed by echocardiography. Treatment of Cav-1 KO mice with telmisartan significantly improved cardiac function compared to age-matched, vehicle treated Cav-1 KO mice, while telmisartan did not affected cardiac function in WT mice. Both left ventricular (LV) weight to body weight ratios and LV to tibial length ratios were also reverted by telmisartan in Cav-1 KO but not WT mice. LV hypertrophy was associated with increased expression of natriuretic peptides-A and –B, β-myosin heavy chain and TGF-β and telmisartan treatment normalized the expression of these genes. Telmisartan reduced the expression of collagen genes (Col1A and Col3A) and associated perivascular fibrosis in intramyocardial vessels in Cav-1 KO mice. In conclusion, telmisartan treatment reduces indexes of cardiac hypertrophy in this unique genetic model of spontaneous LV hypertrophy. PMID:20585312

Parametric Dependencies in Aero-Elastic, Articulated, Flapping Flight

NASA Astrophysics Data System (ADS)

Willis, D. J.; Persson, P.; Peraire, J.; Breuer, K. S.

2006-11-01

Aero-elastic coupling and wing articulation both play a vital role in the generation of lift and propulsion in birds, bats and fish. We present results from a computational study that employs several tools of varying fidelity to explore the role of flexible structures on the performance and efficiency of bird and bat flight mechanics. The tools (both 2-D and 3-D) include a Wake only ``Betz'' analysis following the work of Hall, Pigott and Hall (J. Aircaft, 1998), a potential flow model coupled to a free-vortex wake (Willis, Peraire & White, AIAA 2005-0854), and lastly, a discontinuous Galerkin solver (Persson & Peraire, AIAA 2006-0113) for the full Navier-Stokes equations. Structural models include springs, beams and membranes to represent compliant biological structures. The results demonstrate the changes in efficiency that can be achieved by different parametric variations in the flight behavior, including the effects of increasing kinematic degrees of freedom (e.g. articulated wings) and the effect of compliance in wing and skeletal structures.

User's manual for UCAP: Unified Counter-Rotation Aero-Acoustics Program

NASA Technical Reports Server (NTRS)

Culver, E. M.; Mccolgan, C. J.

1993-01-01

This is the user's manual for the Unified Counter-rotation Aeroacoustics Program (UCAP), the counter-rotation derivative of the UAAP (Unified Aero-Acoustic Program). The purpose of this program is to predict steady and unsteady air loading on the blades and the noise produced by a counter-rotation Prop-Fan. The aerodynamic method is based on linear potential theory with corrections for nonlinearity associated with axial flux induction, vortex lift on the blades, and rotor-to-rotor interference. The theory for acoustics and the theory for individual blade loading and wakes are derived in Unified Aeroacoustics Analysis for High Speed Turboprop Aerodynamics and Noise, Volume 1 (NASA CR-4329). This user's manual also includes a brief explanation of the theory used for the modelling of counter-rotation.

User's manual for UCAP: Unified Counter-Rotation Aero-Acoustics Program

NASA Astrophysics Data System (ADS)

Culver, E. M.; McColgan, C. J.

1993-04-01

This is the user's manual for the Unified Counter-rotation Aeroacoustics Program (UCAP), the counter-rotation derivative of the UAAP (Unified Aero-Acoustic Program). The purpose of this program is to predict steady and unsteady air loading on the blades and the noise produced by a counter-rotation Prop-Fan. The aerodynamic method is based on linear potential theory with corrections for nonlinearity associated with axial flux induction, vortex lift on the blades, and rotor-to-rotor interference. The theory for acoustics and the theory for individual blade loading and wakes are derived in Unified Aeroacoustics Analysis for High Speed Turboprop Aerodynamics and Noise, Volume 1 (NASA CR-4329). This user's manual also includes a brief explanation of the theory used for the modelling of counter-rotation.

On the Development of an Efficient Parallel Hybrid Solver with Application to Acoustically Treated Aero-Engine Nacelles

NASA Technical Reports Server (NTRS)

Watson, Willie R.; Nark, Douglas M.; Nguyen, Duc T.; Tungkahotara, Siroj

2006-01-01

A finite element solution to the convected Helmholtz equation in a nonuniform flow is used to model the noise field within 3-D acoustically treated aero-engine nacelles. Options to select linear or cubic Hermite polynomial basis functions and isoparametric elements are included. However, the key feature of the method is a domain decomposition procedure that is based upon the inter-mixing of an iterative and a direct solve strategy for solving the discrete finite element equations. This procedure is optimized to take full advantage of sparsity and exploit the increased memory and parallel processing capability of modern computer architectures. Example computations are presented for the Langley Flow Impedance Test facility and a rectangular mapping of a full scale, generic aero-engine nacelle. The accuracy and parallel performance of this new solver are tested on both model problems using a supercomputer that contains hundreds of central processing units. Results show that the method gives extremely accurate attenuation predictions, achieves super-linear speedup over hundreds of CPUs, and solves upward of 25 million complex equations in a quarter of an hour.

AeroPropulsoServoElasticity: Dynamic Modeling of the Variable Cycle Propulsion System

NASA Technical Reports Server (NTRS)

Kopasakis, George

2012-01-01

This presentation was made at the 2012 Fundamental Aeronautics Program Technical Conference and it covers research work for the Dynamic Modeling of the Variable cycle Propulsion System that was done under the Supersonics Project, in the area of AeroPropulsoServoElasticity. The presentation covers the objective for the propulsion system dynamic modeling work, followed by the work that has been done so far to model the variable Cycle Engine, modeling of the inlet, the nozzle, the modeling that has been done to model the affects of flow distortion, and finally presenting some concluding remarks and future plans.

Computational fluid dynamics and aerothermodynamics

NASA Technical Reports Server (NTRS)

Carlson, Leland A.

1989-01-01

The primary objective was the development of nonequilibrium radiation and chemistry models suitable for engineering applications associated with the flow fields about aeroassisted orbital transfer vehicles (AOTVs), the aero-assisted flight experiment vehicle (AFE), and other vehicles operating at superorbital velocities and very high attitudes.

Effective L/D: A Theoretical Approach to the Measurement of Aero-Structural Efficiency in Aircraft Design

NASA Technical Reports Server (NTRS)

Guynn, Mark D.

2015-01-01

There are many trade-offs in aircraft design that ultimately impact the overall performance and characteristics of the final design. One well recognized and well understood trade-off is that of wing weight and aerodynamic efficiency. Higher aerodynamic efficiency can be obtained by increasing wing span, usually at the expense of higher wing weight. The proper balance of these two competing factors depends on the objectives of the design. For example, aerodynamic efficiency is preeminent for sailplanes and long slender wings result. Although the wing weight-drag trade is universally recognized, aerodynamic efficiency and structural efficiency are not usually considered in combination. This paper discusses the concept of "aero-structural efficiency," which combines weight and drag characteristics. A metric to quantify aero-structural efficiency, termed effective L/D, is then derived and tested with various scenarios. Effective L/D is found to be a practical and robust means to simultaneously characterize aerodynamic and structural efficiency in the context of aircraft design. The primary value of the effective L/D metric is as a means to better communicate the combined system level impacts of drag and structural weight.

Aero-Optical Wavefront Propagation and Refractive Fluid Interfaces in Large-Reynolds-Number Compressible Turbulent Flows

DTIC Science & Technology

2005-12-31

are utilized with the eikonal equation of geometrical optics to propagate computationally the optical wavefronts in the near field. As long as the...aero-optical interactions. In terms of the refractive index field n and the optical path length (OPL), the eikonal equation is: |∇ (OPL)| = n , (9) (e.g...ray n(`, t) d` . (10) The OPL integral corresponds to inverting the eikonal equation 9. The physical distance along the beam propagation path for

Dosimetric impact of the AeroForm tissue expander in postmastectomy radiation therapy: an ex vivo analysis.

PubMed

Moni, Janaki; Saleeby, Jonathan; Bannon, Elizabeth; Lo, Yuan-Chyuan; Fitzgerald, Thomas J

2015-01-01

To evaluate the effect of the AeroForm (AirXpanders Inc, Palo Alto, CA) tissue expander on the dose distribution in a phantom from a simulated postmastectomy radiation treatment for breast cancer. Experiments were conducted to determine the effect on the dose distribution with the metallic reservoir irradiated independently and with the entire AeroForm tissue expander placed on a RANDO phantom (The Phantom Laboratory, Salem, NY). The metallic reservoir was irradiated on a block of solid water with film at various depths ranging from 0 to 8.2 cm from the surface. The intact 400 cc AeroForm was inflated to full capacity and irradiated while positioned on a RANDO phantom, with 12 optically stimulated luminescent dosimeters (OSLDs) placed at clinically relevant expander-tissue interface points. Film dosimetry with the reservoir perpendicular to film reveals 40% transmission at a depth of 0.7 cm, which increases to 60% at a depth of 8.2 cm. In the parallel position, the results vary depending on which area under the reservoir is examined, indicating that the reservoir is not a uniformly dense object. Testing of the intact expander on the phantom revealed that the average percent difference (measured vs expected dose) was 2.7%, σ = 6.2% with heterogeneity correction and 3.7%, σ = 2.4% without heterogeneity correction. The only position where the OSLD readings were consistently higher than the calculated dose by >5% was at position 1, just deep to the canister at the expander-phantom interface. At this position, the readings varied from 5.2% to 14.5%, regardless of heterogeneity correction. Film dosimetry demonstrated beam attenuation in the shadow of the metallic reservoir in the expander. This decrease in dose was not reproduced on the intact expander on the phantom designed to replicate a clinical setup. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Host model uncertainties in aerosol radiative forcing estimates: results from the AeroCom prescribed intercomparison study

NASA Astrophysics Data System (ADS)

Stier, P.; Schutgens, N. A. J.; Bian, H.; Boucher, O.; Chin, M.; Ghan, S.; Huneeus, N.; Kinne, S.; Lin, G.; Myhre, G.; Penner, J. E.; Randles, C.; Samset, B.; Schulz, M.; Yu, H.; Zhou, C.

2012-09-01

Simulated multi-model "diversity" in aerosol direct radiative forcing estimates is often perceived as measure of aerosol uncertainty. However, current models used for aerosol radiative forcing calculations vary considerably in model components relevant for forcing calculations and the associated "host-model uncertainties" are generally convoluted with the actual aerosol uncertainty. In this AeroCom Prescribed intercomparison study we systematically isolate and quantify host model uncertainties on aerosol forcing experiments through prescription of identical aerosol radiative properties in nine participating models. Even with prescribed aerosol radiative properties, simulated clear-sky and all-sky aerosol radiative forcings show significant diversity. For a purely scattering case with globally constant optical depth of 0.2, the global-mean all-sky top-of-atmosphere radiative forcing is -4.51 W m-2 and the inter-model standard deviation is 0.70 W m-2, corresponding to a relative standard deviation of 15%. For a case with partially absorbing aerosol with an aerosol optical depth of 0.2 and single scattering albedo of 0.8, the forcing changes to 1.26 W m-2, and the standard deviation increases to 1.21 W m-2, corresponding to a significant relative standard deviation of 96%. However, the top-of-atmosphere forcing variability owing to absorption is low, with relative standard deviations of 9% clear-sky and 12% all-sky. Scaling the forcing standard deviation for a purely scattering case to match the sulfate radiative forcing in the AeroCom Direct Effect experiment, demonstrates that host model uncertainties could explain about half of the overall sulfate forcing diversity of 0.13 W m-2 in the AeroCom Direct Radiative Effect experiment. Host model errors in aerosol radiative forcing are largest in regions of uncertain host model components, such as stratocumulus cloud decks or areas with poorly constrained surface albedos, such as sea ice. Our results demonstrate that host

Host model uncertainties in aerosol radiative forcing estimates: results from the AeroCom Prescribed intercomparison study

NASA Astrophysics Data System (ADS)

Stier, P.; Schutgens, N. A. J.; Bellouin, N.; Bian, H.; Boucher, O.; Chin, M.; Ghan, S.; Huneeus, N.; Kinne, S.; Lin, G.; Ma, X.; Myhre, G.; Penner, J. E.; Randles, C. A.; Samset, B.; Schulz, M.; Takemura, T.; Yu, F.; Yu, H.; Zhou, C.

2013-03-01

Simulated multi-model "diversity" in aerosol direct radiative forcing estimates is often perceived as a measure of aerosol uncertainty. However, current models used for aerosol radiative forcing calculations vary considerably in model components relevant for forcing calculations and the associated "host-model uncertainties" are generally convoluted with the actual aerosol uncertainty. In this AeroCom Prescribed intercomparison study we systematically isolate and quantify host model uncertainties on aerosol forcing experiments through prescription of identical aerosol radiative properties in twelve participating models. Even with prescribed aerosol radiative properties, simulated clear-sky and all-sky aerosol radiative forcings show significant diversity. For a purely scattering case with globally constant optical depth of 0.2, the global-mean all-sky top-of-atmosphere radiative forcing is -4.47 Wm-2 and the inter-model standard deviation is 0.55 Wm-2, corresponding to a relative standard deviation of 12%. For a case with partially absorbing aerosol with an aerosol optical depth of 0.2 and single scattering albedo of 0.8, the forcing changes to 1.04 Wm-2, and the standard deviation increases to 1.01 W-2, corresponding to a significant relative standard deviation of 97%. However, the top-of-atmosphere forcing variability owing to absorption (subtracting the scattering case from the case with scattering and absorption) is low, with absolute (relative) standard deviations of 0.45 Wm-2 (8%) clear-sky and 0.62 Wm-2 (11%) all-sky. Scaling the forcing standard deviation for a purely scattering case to match the sulfate radiative forcing in the AeroCom Direct Effect experiment demonstrates that host model uncertainties could explain about 36% of the overall sulfate forcing diversity of 0.11 Wm-2 in the AeroCom Direct Radiative Effect experiment. Host model errors in aerosol radiative forcing are largest in regions of uncertain host model components, such as stratocumulus

Trigeminal ganglion neuron subtype-specific alterations of CaV2.1 calcium current and excitability in a Cacna1a mouse model of migraine

PubMed Central

Fioretti, B; Catacuzzeno, L; Sforna, L; Gerke-Duncan, M B; van den Maagdenberg, A M J M; Franciolini, F; Connor, M; Pietrobon, D

2011-01-01

Abstract Familial hemiplegic migraine type-1 (FHM1), a monogenic subtype of migraine with aura, is caused by gain-of-function mutations in CaV2.1 (P/Q-type) calcium channels. The consequences of FHM1 mutations on the trigeminovascular pathway that generates migraine headache remain largely unexplored. Here we studied the calcium currents and excitability properties of two subpopulations of small-diameter trigeminal ganglion (TG) neurons from adult wild-type (WT) and R192Q FHM1 knockin (KI) mice: capsaicin-sensitive neurons without T-type calcium currents (CS) and capsaicin-insensitive neurons characterized by the expression of T-type calcium currents (CI-T). Small TG neurons retrogradely labelled from the dura are mostly CS neurons, while CI-T neurons were not present in the labelled population. CS and CI-T neurons express CaV2.1 channels with different activation properties, and the CaV2.1 channels are differently affected by the FHM1 mutation in the two TG neuron subtypes. In CI-T neurons from FHM1 KI mice there was a larger P/Q-type current density following mild depolarizations, a larger action potential (AP)-evoked calcium current and a longer AP duration when compared to CI-T neurons from WT mice. In striking contrast, the P/Q-type current density, voltage dependence and kinetics were not altered by the FHM1 mutation in CS neurons. The excitability properties of mutant CS neurons were also unaltered. Congruently, the FHM1 mutation did not alter depolarization-evoked CGRP release from the dura mater, while CGRP release from the trigeminal ganglion was larger in KI compared to WT mice. Our findings suggest that the facilitation of peripheral mechanisms of CGRP action, such as dural vasodilatation and nociceptor sensitization at the meninges, does not contribute to the generation of headache in FHM1. PMID:22005682

Aerosol single-scattering albedo over the global oceans: Comparing PARASOL retrievals with AERONET, OMI, and AeroCom models estimates

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

Lacagnina, Carlo; Hasekamp, Otto P.; Bian, Huisheng

2015-09-27

The aerosol Single Scattering Albedo (SSA) over the global oceans is evaluated based on polarimetric measurements by the PARASOL satellite. The retrieved values for SSA and Aerosol Optical Depth (AOD) agree well with the ground-based measurements of the AErosol RObotic NETwork (AERONET). The global coverage provided by the PARASOL observations represents a unique opportunity to evaluate SSA and AOD simulated by atmospheric transport model runs, as performed in the AeroCom framework. The SSA estimate provided by the AeroCom models is generally higher than the SSA retrieved from both PARASOL and AERONET. On the other hand, the mean simulated AOD ismore » about right or slightly underestimated compared with observations. An overestimate of the SSA by the models would suggest that these simulate an overly strong aerosol radiative cooling at top-of-atmosphere (TOA) and underestimate it at surface. This implies that aerosols have a potential stronger impact within the atmosphere than currently simulated.« less

The Role of Free-Stream Turbulence on High Pressure Turbine Aero-Thermal Stage Interaction

NASA Astrophysics Data System (ADS)

Kopriva, James Earl

Turbulence plays an important role on the aero-thermal performance of modern aircraft engine High Pressure Turbines (HPT). The role of the vane wake and passage turbulence on the downstream blade flow field is an important consideration for both performance and durability. Obtaining measurements to fully characterize the flow field can be challenging and costly in an experimental facility. Advances in computational Fluid Dynamic (CFD) modeling and High Performance Computing (HPC) are providing opportunity to close these measurement gaps. In order for CFD to be adopted, methods need to be both accurate and efficient. Meshing approaches must also be able to resolve complex HPT geometry while maintaining quality adequate for scale-resolved simulations. Therefore, the accuracy of executing scale-resolved simulations with a second-order code on a mesh of prisms and tetrahedrals in Fluent is considered. Before execution of the HPT computational study, a building block approach is taken to gain quantified predictive performance in the modeling approach as well as understanding limitations in lower computational cost modeling approaches. The predictive capability for Reynolds Averaged Navier Stokes (RANS), Hybrid Large Eddy Simulation (LES), and wall-resolved LES turbulence modeling approaches are first assessed for a cylinder in cross-flow at a Reynolds number of 2580. The flow condition and simple geometry facilitate a quick turn-around for modeling assessment before moving the HPT vane study at high Reynolds and Mach number conditions. Modeling approaches are then assessed relative to the experimental measurements of Arts and Rouvroit (1992) on a pitch-line HPT uncooled vane at high Mach and Reynolds numbers conditions with low (0-6%) free-stream turbulence. The current unstructured second-order LES approach agrees with experimental data and is found to be within the equivalent experimental uncertainty when compared to the structured high-ordered solver FDL3DI. The

HTS machines as enabling technology for all-electric airborne vehicles

NASA Astrophysics Data System (ADS)

Masson, P. J.; Brown, G. V.; Soban, D. S.; Luongo, C. A.

2007-08-01

Environmental protection has now become paramount as evidence mounts to support the thesis of human activity-driven global warming. A global reduction of the emissions of pollutants into the atmosphere is therefore needed and new technologies have to be considered. A large part of the emissions come from transportation vehicles, including cars, trucks and airplanes, due to the nature of their combustion-based propulsion systems. Our team has been working for several years on the development of high power density superconducting motors for aircraft propulsion and fuel cell based power systems for aircraft. This paper investigates the feasibility of all-electric aircraft based on currently available technology. Electric propulsion would require the development of high power density electric propulsion motors, generators, power management and distribution systems. The requirements in terms of weight and volume of these components cannot be achieved with conventional technologies; however, the use of superconductors associated with hydrogen-based power plants makes possible the design of a reasonably light power system and would therefore enable the development of all-electric aero-vehicles. A system sizing has been performed both for actuators and for primary propulsion. Many advantages would come from electrical propulsion such as better controllability of the propulsion, higher efficiency, higher availability and less maintenance needs. Superconducting machines may very well be the enabling technology for all-electric aircraft development.

Combined Loads Test Fixture for Thermal-Structural Testing Aerospace Vehicle Panel Concepts

NASA Technical Reports Server (NTRS)

Fields, Roger A.; Richards, W. Lance; DeAngelis, Michael V.

2004-01-01

A structural test requirement of the National Aero-Space Plane (NASP) program has resulted in the design, fabrication, and implementation of a combined loads test fixture. Principal requirements for the fixture are testing a 4- by 4-ft hat-stiffened panel with combined axial (either tension or compression) and shear load at temperatures ranging from room temperature to 915 F, keeping the test panel stresses caused by the mechanical loads uniform, and thermal stresses caused by non-uniform panel temperatures minimized. The panel represents the side fuselage skin of an experimental aerospace vehicle, and was produced for the NASP program. A comprehensive mechanical loads test program using the new test fixture has been conducted on this panel from room temperature to 500 F. Measured data have been compared with finite-element analyses predictions, verifying that uniform load distributions were achieved by the fixture. The overall correlation of test data with analysis is excellent. The panel stress distributions and temperature distributions are very uniform and fulfill program requirements. This report provides details of an analytical and experimental validation of the combined loads test fixture. Because of its simple design, this unique test fixture can accommodate panels from a variety of aerospace vehicle designs.

A Modular Aero-Propulsion System Simulation of a Large Commercial Aircraft Engine

NASA Technical Reports Server (NTRS)

DeCastro, Jonathan A.; Litt, Jonathan S.; Frederick, Dean K.

2008-01-01

A simulation of a commercial engine has been developed in a graphical environment to meet the increasing need across the controls and health management community for a common research and development platform. This paper describes the Commercial Modular Aero Propulsion System Simulation (C-MAPSS), which is representative of a 90,000-lb thrust class two spool, high bypass ratio commercial turbofan engine. A control law resembling the state-of-the-art on board modern aircraft engines is included, consisting of a fan-speed control loop supplemented by relevant engine limit protection regulator loops. The objective of this paper is to provide a top-down overview of the complete engine simulation package.

AeroVironment Technician Marshall MacCready carefully lays a panel of solar cells into place on a wi

NASA Technical Reports Server (NTRS)

2000-01-01

Technician Marshall MacCready carefully lays a panel of solar cells into place on a wing section of the Helios Prototype flying wing at AeroVironment's Design Development Center in Simi Valley, California. More than 1,800 panels containing some 64,000 bi-facial cells, fabricated by SunPower, Inc., of Sunnyvale, California, have been installed on the solar-powered aircraft to provide electricity to its 14 motors and operating systems. Developed by AeroVironment under NASA's Environmental Research Aircraft and Sensor Technology (ERAST) project, the Helios Prototype is the forerunner of a planned fleet of slow-flying, long duration, high-altitude aircraft which can perform atmospheric science missions and serve as telecommunications relay platforms in the stratosphere. Target goals set by NASA for the giant 246-foot span flying wing include reaching and sustaining subsonic horizontal flight at 100,000 feet altitude in 2001, and sustained continuous flight for at least four days and nights above 50,000 feet altitude 2003 with the aid of a regenerative fuel cell-based energy storage system now being developed.

Imbalance of caveolin-1 and eNOS expression in the pulmonary vasculature of experimental diaphragmatic hernia.

PubMed

Hofmann, Alejandro; Gosemann, Jan-Hendrik; Takahashi, Toshiaki; Friedmacher, Florian; Duess, Johannes W; Puri, Prem

2014-08-01

Caveolin-1 (Cav-1) exerts major regulatory functions on intracellular signaling pathways originating at the plasma membrane. Cav-1 is a key regulator in adverse lung remodeling and the development of pulmonary hypertension (PH) regulating vasomotor tone through its ability to reduce nitric oxide (NO) production. This low-output endothelial NO synthase (eNOS) derived NO maintains normal pulmonary vascular homeostasis. Cav-1 deficiency leads to increased bioavailability of NO, which has been linked to increased nitrosative stress. Inhibition of eNOS reduced oxidant production and reversed PH, supporting the concept that Cav-1 regulation of eNOS activity is crucial to endothelial homeostasis in lungs. We designed this study to investigate the hypothesis that expression of Cav-1 is downregulated while eNOS expression is upregulated by the pulmonary endothelium in the nitrofen-induced congenital diaphragmatic hernia (CDH). Pregnant rats were exposed to nitrofen or vehicle on day 9.5 (D9.5). Fetuses were sacrificed on D21 and divided into nitrofen and control groups. Quantitative real-time polymerase chain reaction, Western blotting, and confocal immunofluorescence were performed to determine pulmonary gene expression levels and protein expression of Cav-1 and eNOS. Pulmonary Cav-1 gene expression levels were significantly decreased, while eNOS gene expression was significantly increased in nitrofen-induced CDH(+). Western blotting and confocal microscopy revealed decreased pulmonary Cav-1 protein expression, while eNOS protein expression was increased in CDH(+) compared to controls. The striking evidence of markedly decreased gene and protein expression of Cav-1 with concurrently increased eNOS gene and protein expression in the pulmonary vasculature suggests that activation of eNOS secondary to Cav-1 deficiency may play an important role in the pathogenesis of PH in the nitrofen-induced CDH. © 2014 Wiley Periodicals, Inc.

Human Factors Validation of the AeroForm Tissue Expander System for Breast Reconstruction.

PubMed

Kelley, Kathy; Kim, Jennie

The tissue expansion process using traditional saline expanders is lengthy and uncomfortable. A new technology has been developed, providing a needle-free option implanted after a mastectomy, and is activated by a handheld remote control releasing small amounts (10 cc) of carbon dioxide from an internal reservoir. The expander is gradually filled with CO2 resulting in mechanical stretching of the overlying tissue. The AeroForm System has been evaluated in a series of clinical trials including a randomized, controlled U.S. study comparing the AeroForm System with saline expanders. Results demonstrated patients can safely and reliably dose and complete their expansions in half the time compared to saline expanders. A human factors validation study was conducted in 8 patients to evaluate whether patients could correctly use the device to complete their expansion at home. The sessions were recorded and data on performance, behavioral, and subjective measures were collected and analyzed and submitted to the FDA as part of the U.S. marketing approval. All 8 participants were successful in using the controller to deliver a simulated dose. Participants found the device easy to use and the training material provided adequate to understand use of the controller. For women who choose 2-stage breast reconstruction, a new safe and effective option is available for tissue expansion, offering a convenient and empowering alternative. The human factors validation study conducted confirmed the simplicity of the device and further validated that the device can be used safely and effectively for breast tissue expansion.

Dynamic performance of an aero-assist spacecraft - AFE

NASA Technical Reports Server (NTRS)

Chang, Ho-Pen; French, Raymond A.

1992-01-01

Dynamic performance of the Aero-assist Flight Experiment (AFE) spacecraft was investigated using a high-fidelity 6-DOF simulation model. Baseline guidance logic, control logic, and a strapdown navigation system to be used on the AFE spacecraft are also modeled in the 6-DOF simulation. During the AFE mission, uncertainties in the environment and the spacecraft are described by an error space which includes both correlated and uncorrelated error sources. The principal error sources modeled in this study include navigation errors, initial state vector errors, atmospheric variations, aerodynamic uncertainties, center-of-gravity off-sets, and weight uncertainties. The impact of the perturbations on the spacecraft performance is investigated using Monte Carlo repetitive statistical techniques. During the Solid Rocket Motor (SRM) deorbit phase, a target flight path angle of -4.76 deg at entry interface (EI) offers very high probability of avoiding SRM casing skip-out from the atmosphere. Generally speaking, the baseline designs of the guidance, navigation, and control systems satisfy most of the science and mission requirements.

Development of pH-responsive biopolymer-silica composites loaded with Larrea divaricata Cav. extract with antioxidant activity.

PubMed

Alvarez Echazú, María Inés; Olivetti, Christian Ezequiel; Peralta, Ignacio; Alonso, Maria Rosario; Anesini, Claudia; Perez, Claudio Javier; Alvarez, Gisela Solange; Desimone, Martin Federico

2018-05-07

A detailed study of biomaterials is mandatory to comprehend their feasible biomedical applications in terms of drug delivery and tissue regeneration. Particularly, mucoadhesive biopolymers such as chitosan (chi) and carboxymethylcellulose (CMC) have become interesting biomaterials regards to their biocompatibility and non-toxicity for oral mucosal drug delivery. In this work, pH-responsive biopolymer-silica composites (Chi-SiO 2 , Chi-CMC-SiO 2 ) were developed. These two types of composites presented a different swelling behavior due to the environmental pH. Moreover, the nanocomposites were loaded with aqueous Larrea divaricata Cav. extract (Ld), a South American plant which presents antioxidant properties suitable for the treatment of gingivoperiodontal diseases. Chi-CMC-SiO 2 composites showed the highest incorporation and reached the 100% of extract release in almost 4 days while they preserved their antioxidant properties. In this study, thermal and swelling behavior were pointed out to show the distinct water-composite interaction and therefore to evaluate their mucoadhesivity. Furthermore, a cytotoxicity test with 3T3 fibroblasts was assessed, showing that in both composites the addition of Larrea divaricata Cav. extract increased fibroblast proliferation. Lastly, preliminary in vitro studies were performed with simulated body fluids. Indeed, SEM-EDS analysis indicated that only chi-SiO 2 composite may provide an environment for possible biomineralization while the addition of CMC to the composites discouraged calcium accumulation. In conclusion, the development of bioactive composites could promote the regeneration of periodontal tissue damaged throughout periodontal disease and the presence of silica nanoparticles could provide an environment for biomineralization. Copyright © 2018 Elsevier B.V. All rights reserved.

Fuselage boundary-layer refraction of fan tones radiated from an installed turbofan aero-engine.

PubMed

Gaffney, James; McAlpine, Alan; Kingan, Michael J

2017-03-01

A distributed source model to predict fan tone noise levels of an installed turbofan aero-engine is extended to include the refraction effects caused by the fuselage boundary layer. The model is a simple representation of an installed turbofan, where fan tones are represented in terms of spinning modes radiated from a semi-infinite circular duct, and the aircraft's fuselage is represented by an infinitely long, rigid cylinder. The distributed source is a disk, formed by integrating infinitesimal volume sources located on the intake duct termination. The cylinder is located adjacent to the disk. There is uniform axial flow, aligned with the axis of the cylinder, everywhere except close to the cylinder where there is a constant thickness boundary layer. The aim is to predict the near-field acoustic pressure, and in particular, to predict the pressure on the cylindrical fuselage which is relevant to assess cabin noise. Thus no far-field approximations are included in the modelling. The effect of the boundary layer is quantified by calculating the area-averaged mean square pressure over the cylinder's surface with and without the boundary layer included in the prediction model. The sound propagation through the boundary layer is calculated by solving the Pridmore-Brown equation. Results from the theoretical method show that the boundary layer has a significant effect on the predicted sound pressure levels on the cylindrical fuselage, owing to sound radiation of fan tones from an installed turbofan aero-engine.

Real-time analysis of ambient organic aerosols using aerosol flowing atmospheric-pressure afterglow mass spectrometry (AeroFAPA-MS)

NASA Astrophysics Data System (ADS)

Brüggemann, Martin; Karu, Einar; Stelzer, Torsten; Hoffmann, Thorsten

2015-04-01

Organic aerosol accounts for a major fraction of atmospheric aerosols and has implications on the earth's climate and human health. However, due to the chemical complexity its measurement remains a major challenge for analytical instrumentation.1 Here, we present the development, characterization and application of a new soft ionization technique that allows mass spectrometric real-time detection of organic compounds in ambient aerosols. The aerosol flowing atmospheric-pressure afterglow (AeroFAPA) ion source utilizes a helium glow discharge plasma to produce excited helium species and primary reagent ions. Ionization of the analytes occurs in the afterglow region after thermal desorption and results mainly in intact molecular ions, facilitating the interpretation of the acquired mass spectra. In the past, similar approaches were used to detect pesticides, explosives or illicit drugs on a variety of surfaces.2,3 In contrast, the AeroFAPA source operates 'online' and allows the detection of organic compounds in aerosols without a prior precipitation or sampling step. To our knowledge, this is the first application of an atmospheric-pressure glow discharge ionization technique to ambient aerosol samples. We illustrate that changes in aerosol composition and concentration are detected on the time scale of seconds and in the ng-m-3 range. Additionally, the successful application of AeroFAPA-MS during a field study in a mixed forest region in Central Europe is presented. Several oxidation products of monoterpenes were clearly identified using the possibility to perform tandem MS experiments. The acquired data are in agreement with previous studies and demonstrate that AeroFAPA-MS is a suitable tool for organic aerosol analysis. Furthermore, these results reveal the potential of this technique to enable new insights into aerosol formation, growth and transformation in the atmosphere. References: 1) IPCC, 2013: Summary for Policymakers. In: Climate Change 2013: The

Evaluation of aero Commander propeller acoustic data: Static operations

NASA Technical Reports Server (NTRS)

Piersol, A. G.; Wilby, E. G.; Wilby, J. F.

1978-01-01

Acoustic data are analyzed from a series of ground tests performed on an Aero Commander propeller-driven aircraft with an array of microphones flush-mounted on one side of the fuselage. The analyses were concerned with the propeller blade passage noise during static operation at several different engine speeds and included calculations of the magnitude and phase of the blade passage tones, the amplitude stability of the tones, and the spatial phase and coherence of the tones. The results indicate that the pressure field impinging on the fuselage represents primarily aerodynamic (near field) effects in the plane of the propeller at all frequencies. Forward and aft of the propeller plane aerodynamic effects still dominate the pressure field at frequencies below 200 Hz; but at higher frequencies, the pressure field is due to acoustic propagation from an equivalent center located about 0.15 to 0.30 blade diameters inboard from the propeller hub.

Investigation on flow oscillation modes and aero-acoustics generation mechanism in cavity

NASA Astrophysics Data System (ADS)

Yang, Dang-Guo; Lu, Bo; Cai, Jin-Sheng; Wu, Jun-Qiang; Qu, Kun; Liu, Jun

2018-05-01

Unsteady flow and multi-scale vortex transformation inside a cavity of L/D = 6 (ratio of length to depth) at Ma = 0.9 and 1.5 were studied using the numerical simulation method of modified delayed detached eddy simulation (DDES) in this paper. Aero-acoustic characteristics for the cavity at same flow conditions were obtained by the numerical method and 0.6 m by 0.6 m transonic and supersonic wind-tunnel experiments. The analysis on the computational and experimental results indicates that some vortex generates from flow separation in shear-layer over the cavity, and the vortex moves from forward to downward of the cavity at some velocity, and impingement of the vortex and the rear-wall of the cavity occurs. Some sound waves spread abroad to the cavity fore-wall, which induces some new vortex generation, and the vortex sheds, moves and impinges on the cavity rear-wall. New sound waves occur. The research results indicate that sound wave feedback created by the impingement of the shedding-vortices and rear cavity face leads to flow oscillations and noise generation inside the cavity. Analysis on aero-acoustic characteristics inside the cavity is feasible. The simulated self-sustained flow-oscillation modes and peak sound pressure on typical frequencies inside the cavity agree well with Rossiter’s and Heller’s predicated results. Moreover, the peak sound pressure occurs in the first and second flow-oscillation modes and most of sound energy focuses on the low-frequency region. Compared with subsonic speed (Ma = 0.9), aerodynamic noise is more intense at Ma = 1.5, which is induced by compression wave or shock wave in near region of fore and rear cavity face.

Ka-band MMIC array system for ACTS aeronautical terminal experiment (Aero-X)

NASA Technical Reports Server (NTRS)

Raquet, Charles A.; Zakrajsek, Robert J.; Lee, Richard Q.; Andro, Monty; Turtle, John P.

1995-01-01

During the summer of 1994, the Advanced Communication Technology Satellite (ACTS) Aeronautical Terminal Experiment (Aero-X) was successfully completed by the NASA Lewis Research Center (LeRC) and the Jet Propulsion Laboratory (JPL). 4.8 and 9.6 Kbps duplex voice links were established between the LeRC Learjet and the ACTS Link Evaluation Terminal (LET) in Cleveland, Ohio, via the ACTS. The antenna system used in this demonstration was developed by LeRC and featured LeRC and US Air Force experimental arrays using GaAs MMIC devices at each radiating element for electronic beam steering and distributed power amplification. The antenna system consisted of three arrays mounted inside the LeRC Learjet, pointing out through the windows. An open loop tracking controller developed by LeRC used information from the aircraft position and attitude sensors to automatically steer the arrays toward ACTS during flight JPL ACTS Mobile Terminal (AMT) system hardware was used as transceivers both on the aircraft and at the LET. The single 32 element MMIC transmit array developed by NASA/LeRC and Texas Instruments has an EIRP of 23.4 dBW at boresight. The two 20 GHz MMIC receive arrays were developed in a cooperative effort with the USAF Rome Laboratory/Electronic System Center, taking advantage of existing USAF array development contracts with Boeing and Martin Marietta. The Boeing array has 23 elements and a G/T of 16/6 db/degK at boresight. The Martin Marietta array has 16 elements and a G/T of 16.1 db/degK at boresight. The three proof-of-concept arrays, the array control system and their integration and operation in the Learjet for Aero-X are described.

Bringing smart transport to Texans : ensuring the benefits of a connected and autonomous transport system in Texas--final report.

DOT National Transportation Integrated Search

2016-11-01

Link to appendices is included. : This project develops and demonstrates a variety of smart-transport technologies, policies, and practices for : highways and freeways using connected autonomous vehicles (CAVs), smartphones, roadside equipment, and r...

Aero-Propulsive Model Design from a Commercial Aircraft in Climb and Cruise Regime using Performance Data =

NASA Astrophysics Data System (ADS)

Tudor, Magdalena

IATA has estimated, in 2012, at about 2% of global carbon dioxide emissions, the environmental impact of the air transport, as a consequence caused by the rapidly growing of global movement demand of people and goods, and which was effectively taken into account in the development of the aviation industry. The historic achievements of scientific and technical progress in the field of commercial aviation were contributed to this estimate, and even today the research continues to make progress to help to reduce the emissions of greenhouse gases. Advances in commercial aircraft, and its engine design technology had the aim to improve flight performance. These improvements have enhanced the global flight planning of these types of aircrafts. Almost all of these advances rely on generated performance data as reference sources, the most of which are classified as "confidential" by the aircraft manufacturers. There are very few aero-propulsive models conceived for the climb regime in the literature, but none of them was designed without access to an engine database, and/or to performance data in climb and in cruise regimes with direct applicability for flight optimization. In this thesis, aero-propulsive models methodologies are proposed for climb and cruise regimes, using system identification and validation methods, through which airplane performance can be computed and stored in the most compact and easily accessible format for this kind of performance data. The acquiring of performance data in this format makes it possible to optimize flight profiles, used by on-board Flight Management Systems. The aero-propulsive models developed here were investigated on two aircrafts belonging to commercial class, and both of them had offered very good accuracy. One of their advantages is that they can be adapted to any other aircraft of the same class, even if there is no access to their corresponding engine flight data. In addition, these models could save airlines a considerable

Thermodynamic Linkage Between Calmodulin Domains Binding Calcium and Contiguous Sites in the C-Terminal Tail of CaV1.2

PubMed Central

Evans, T. Idil Apak; Hell, Johannes; Shea, Madeline A.

2011-01-01

Calmodulin (CaM) binding to the intracellular C-terminal tail (CTT) of the cardiac L-type Ca2+ channel (CaV1.2) regulates Ca2+ entry by recognizing sites that contribute to negative feedback mechanisms for channel closing. CaM associates with CaV1.2 under low resting [Ca2+], but is poised to change conformation and position when intracellular [Ca2+] rises. CaM binding Ca2+, and the domains of CaM binding the CTT are linked thermodynamic functions. To better understand regulation, we determined the energetics of CaM domains binding to peptides representing pre-IQ sites A1588, and C1614 and the IQ motif studied as overlapping peptides IQ1644 and IQ′1650 as well as their effect on calcium binding. (Ca2+)4-CaM bound to all four peptides very favorably (Kd ≤ 2 nM). Linkage analysis showed that IQ1644–1670 bound with a Kd ~1 pM. In the pre-IQ region, (Ca2+)2-N-domain bound preferentially to A1588, while (Ca2+)2-C-domain preferred C1614. When bound to C1614, calcium binding in the N-domain affected the tertiary conformation of the C-domain. Based on the thermodynamics, we propose a structural mechanism for calcium-dependent conformational change in which the linker between CTT sites A and C buckles to form an A-C hairpin that is bridged by calcium-saturated CaM. PMID:21757287

Reliability Estimation of Aero-engine Based on Mixed Weibull Distribution Model

NASA Astrophysics Data System (ADS)

Yuan, Zhongda; Deng, Junxiang; Wang, Dawei

2018-02-01

Aero-engine is a complex mechanical electronic system, based on analysis of reliability of mechanical electronic system, Weibull distribution model has an irreplaceable role. Till now, only two-parameter Weibull distribution model and three-parameter Weibull distribution are widely used. Due to diversity of engine failure modes, there is a big error with single Weibull distribution model. By contrast, a variety of engine failure modes can be taken into account with mixed Weibull distribution model, so it is a good statistical analysis model. Except the concept of dynamic weight coefficient, in order to make reliability estimation result more accurately, three-parameter correlation coefficient optimization method is applied to enhance Weibull distribution model, thus precision of mixed distribution reliability model is improved greatly. All of these are advantageous to popularize Weibull distribution model in engineering applications.

Integrating Emerging Data Sources Into Operational Practice

DOT National Transportation Integrated Search

2018-05-15

Agencies have the potential to collect, use, and share data from connected and automated vehicles (CAV), connected travelers, and connected infrastructure elements to improve the performance of their traffic management systems and traffic management ...

The development of a droplet-vitrification method to conserve Vitis collections in the USDA-ARS National Plant Germplasm System and UDESC-CAV Santa Catarina State University in Brazil

USDA-ARS?s Scientific Manuscript database

Both the United States and Brazil maintain vast collections of grape genetic resources. We share a common interest in using cryopreservation methods for the secure, long-term back-up of accessions within these field collections of the USDA-ARS National Plant Germplasm System and UDESC-CAV Santa Cata...

An impulsive receptance technique for the time domain computation of the vibration of a whole aero-engine model with nonlinear bearings

NASA Astrophysics Data System (ADS)

Hai, Pham Minh; Bonello, Philip

2008-12-01

The direct study of the vibration of real engine structures with nonlinear bearings, particularly aero-engines, has been severely limited by the fact that current nonlinear computational techniques are not well-suited for complex large-order systems. This paper introduces a novel implicit "impulsive receptance method" (IRM) for the time domain analysis of such structures. The IRM's computational efficiency is largely immune to the number of modes used and dependent only on the number of nonlinear elements. This means that, apart from retaining numerical accuracy, a much more physically accurate solution is achievable within a short timeframe. Simulation tests on a realistically sized representative twin-spool aero-engine showed that the new method was around 40 times faster than a conventional implicit integration scheme. Preliminary results for a given rotor unbalance distribution revealed the varying degree of journal lift, orbit size and shape at the example engine's squeeze-film damper bearings, and the effect of end-sealing at these bearings.

Fe²⁺ block and permeation of CaV3.1 (α1G) T-type calcium channels: candidate mechanism for non-transferrin-mediated Fe²⁺ influx.

PubMed

Lopin, Kyle V; Gray, I Patrick; Obejero-Paz, Carlos A; Thévenod, Frank; Jones, Stephen W

2012-12-01

Iron is a biologically essential metal, but excess iron can cause damage to the cardiovascular and nervous systems. We examined the effects of extracellular Fe²⁺ on permeation and gating of Ca(V)3.1 channels stably transfected in HEK293 cells, by using whole-cell recording. Precautions were taken to maintain iron in the Fe²⁺ state (e.g., use of extracellular ascorbate). With the use of instantaneous I-V currents (measured after strong depolarization) to isolate the effects on permeation, extracellular Fe²⁺ rapidly blocked currents with 2 mM extracellular Ca²⁺ in a voltage-dependent manner, as described by a Woodhull model with K(D) = 2.5 mM at 0 mV and apparent electrical distance δ = 0.17. Extracellular Fe²⁺ also shifted activation to more-depolarized voltages (by ∼10 mV with 1.8 mM extracellular Fe²⁺) somewhat more strongly than did extracellular Ca²⁺ or Mg²⁺, which is consistent with a Gouy-Chapman-Stern model with surface charge density σ = 1 e(-)/98 Ų and K(Fe) = 4.5 M⁻¹ for extracellular Fe²⁺. In the absence of extracellular Ca²⁺ (and with extracellular Na⁺ replaced by TEA), Fe²⁺ carried detectable, whole-cell, inward currents at millimolar concentrations (73 ± 7 pA at -60 mV with 10 mM extracellular Fe²⁺). With a two-site/three-barrier Eyring model for permeation of Ca(V)3.1 channels, we estimated a transport rate for Fe²⁺ of ∼20 ions/s for each open channel at -60 mV and pH 7.2, with 1 μM extracellular Fe²⁺ (with 2 mM extracellular Ca²⁺). Because Ca(V)3.1 channels exhibit a significant "window current" at that voltage (open probability, ∼1%), Ca(V)3.1 channels represent a likely pathway for Fe²⁺ entry into cells with clinically relevant concentrations of extracellular Fe²⁺.

AeroVironment's Jim Daley, Rik Meininger, Derek Lisoski and Wyatt Sadler (clockwise from bottom left) closely monitor systems testing of the Pathfinder-Plus.

NASA Image and Video Library

2004-09-17

AeroVironment's test director Jim Daley, backup pilot Rik Meininger, stability and controls engineer Derek Lisoski and pilot Wyatt Sadler (clockwise from bottom left) closely monitor systems testing of the Pathfinder-Plus solar aircraft from the control station.

A study of the cleft region using synoptic ionospheric plasma data obtained by the polar orbiting satellites Aeros-B and Isis-2

NASA Technical Reports Server (NTRS)

Kist, R.; Klumpar, D.

1980-01-01

The concentrations of O(+) and NO(+) in the dayside high-latitude cleft region of the ionosphere are investigated based on synoptic particle and plasma measurements obtained by the polar orbiting Aeros-B and Isis-2 satellites. At a time when the orbital planes of the satellites are almost at right angles to each other, three maxima in ion temperature are observed, with two of them accompanied by an increased electron temperature and electron density irregularities, and the density of the molecular ions NO(+) and O2(+) is found to increase at the expense of O(+) density. Results are discussed in terms of a theory relating perpendicular electric fields to oxygen atom reaction rates. Systematic analysis of the Aeros data base reveals 14 additional instances of O(+) to NO(+) conversion, with a large variety of forms and structures reflecting the complex structure and dynamics of the high-latitude dayside ionosphere.

Alternative Fuels Data Center

Science.gov Websites

network. The Advisory Council will review state motor vehicle laws and make recommendations for tools and strategies that can be used to prepare Delaware's transportation network for CAVs. The Advisory Council will

On the precision of aero-thermal simulations for TMT

NASA Astrophysics Data System (ADS)

Vogiatzis, Konstantinos; Thompson, Hugh

2016-08-01

Environmental effects on the Image Quality (IQ) of the Thirty Meter Telescope (TMT) are estimated by aero-thermal numerical simulations. These simulations utilize Computational Fluid Dynamics (CFD) to estimate, among others, thermal (dome and mirror) seeing as well as wind jitter and blur. As the design matures, guidance obtained from these numerical experiments can influence significant cost-performance trade-offs and even component survivability. The stochastic nature of environmental conditions results in the generation of a large computational solution matrix in order to statistically predict Observatory Performance. Moreover, the relative contribution of selected key subcomponents to IQ increases the parameter space and thus computational cost, while dictating a reduced prediction error bar. The current study presents the strategy followed to minimize prediction time and computational resources, the subsequent physical and numerical limitations and finally the approach to mitigate the issues experienced. In particular, the paper describes a mesh-independence study, the effect of interpolation of CFD results on the TMT IQ metric, and an analysis of the sensitivity of IQ to certain important heat sources and geometric features.

Pressure and temperature fields associated with aero-optics tests. [transonic wind tunnel tests

NASA Technical Reports Server (NTRS)

Raman, K. R.

1980-01-01

The experimental investigation carried out in a 6 x 6 ft wind tunnel on four model configurations in the aero-optics series of tests are described. The data obtained on the random pressures (static and total pressures) and total temperatures are presented. In addition, the data for static pressure fluctuations on the Coelostat turret model are presented. The measurements indicate that the random pressures and temperature are negligible compared to their own mean (or steady state) values for the four models considered, thus allowing considerable simplification in the calculations to obtain the statistical properties of the density field. In the case of the Coelostat model tests these simplifications cannot be assumed a priori and require further investigation.

Transient aero-thermal mapping of passive Thermal Protection system for nose-cap of Reusable Hypersonic Vehicle

NASA Astrophysics Data System (ADS)

Mahulikar, Shripad P.; Khurana, Shashank; Dungarwal, Ritesh; Shevakari, Sushil G.; Subramanian, Jayakumar; Gujarathi, Amit V.

2008-12-01

The temperature field history of passive Thermal Protection System (TPS) material at the nose-cap (forward stagnation region) of a Reusable Hypersonic Vehicle (RHV) is generated. The 3-D unsteady heat transfer model couples conduction in the solid with external convection and radiation that are modeled as time-varying boundary conditions on the surface. Results are presented for the following two cases: (1) nose-cap comprised of ablative TPS material only (SIRCA/PICA), and (2) nose-cap comprised of a combination of ablative TPS material with moderate thermal conductivity and insulative TPS material. Comparison of the temperature fields of SIRCA and PICA [Case (1)] indicates lowering of the peak stagnation region temperatures for PICA, due to its higher thermal conductivity. Also, the use of PICA and insulative TPS [Case (2)] for the nose-cap has higher potential for weight reduction than the use of ablative TPS alone.

Benefits to the Simulation Training Community of a New ANSI Standard for the Exchange of Aero Simulation Models

NASA Technical Reports Server (NTRS)

Hildreth, Bruce L.; Jackson, E. Bruce

2009-01-01

The American Institute of Aeronautics Astronautics (AIAA) Modeling and Simulation Technical Committee is in final preparation of a new standard for the exchange of flight dynamics models. The standard will become an ANSI standard and is under consideration for submission to ISO for acceptance by the international community. The standard has some a spects that should provide benefits to the simulation training community. Use of the new standard by the training simulation community will reduce development, maintenance and technical refresh investment on each device. Furthermore, it will significantly lower the cost of performing model updates to improve fidelity or expand the envelope of the training device. Higher flight fidelity should result in better transfer of training, a direct benefit to the pilots under instruction. Costs of adopting the standard are minimal and should be paid back within the cost of the first use for that training device. The standard achie ves these advantages by making it easier to update the aerodynamic model. It provides a standard format for the model in a custom eXtensible Markup Language (XML) grammar, the Dynamic Aerospace Vehicle Exchange Markup Language (DAVE-ML). It employs an existing XML grammar, MathML, to describe the aerodynamic model in an input data file, eliminating the requirement for actual software compilation. The major components of the aero model become simply an input data file, and updates are simply new XML input files. It includes naming and axis system conventions to further simplify the exchange of information.

Aerodynamics of a bio-inspired flexible flapping-wing micro air vehicle.

PubMed

Nakata, T; Liu, H; Tanaka, Y; Nishihashi, N; Wang, X; Sato, A

2011-12-01

MAVs (micro air vehicles) with a maximal dimension of 15 cm and nominal flight speeds of around 10 m s⁻¹, operate in a Reynolds number regime of 10⁵ or lower, in which most natural flyers including insects, bats and birds fly. Furthermore, due to their light weight and low flight speed, the MAVs' flight characteristics are substantially affected by environmental factors such as wind gust. Like natural flyers, the wing structures of MAVs are often flexible and tend to deform during flight. Consequently, the aero/fluid and structural dynamics of these flyers are closely linked to each other, making the entire flight vehicle difficult to analyze. We have recently developed a hummingbird-inspired, flapping flexible wing MAV with a weight of 2.4-3.0 g and a wingspan of 10-12 cm. In this study, we carry out an integrated study of the flexible wing aerodynamics of this flapping MAV by combining an in-house computational fluid dynamic (CFD) method and wind tunnel experiments. A CFD model that has a realistic wing planform and can mimic realistic flexible wing kinematics is established, which provides a quantitative prediction of unsteady aerodynamics of the four-winged MAV in terms of vortex and wake structures and their relationship with aerodynamic force generation. Wind tunnel experiments further confirm the effectiveness of the clap and fling mechanism employed in this bio-inspired MAV as well as the importance of the wing flexibility in designing small flapping-wing MAVs.

Argentinean propolis from Zuccagnia punctata Cav. (Caesalpinieae) exudates: phytochemical characterization and antifungal activity.

PubMed

Agüero, María Belén; Gonzalez, Mariela; Lima, Beatriz; Svetaz, Laura; Sánchez, Marianela; Zacchino, Susana; Feresin, Gabriela Egly; Schmeda-Hirschmann, Guillermo; Palermo, Jorge; Wunderlin, Daniel; Tapia, Alejandro

2010-01-13

This paper reports the in vitro antifungal activity of propolis extracts from the province of Tucuman (Argentina) as well as the identification of their main antifungal compounds and botanical origin. The antifungal activity was determined by the microdilution technique, using reference microorganisms and clinical isolates. All dermatophytes and yeasts tested were strongly inhibited by different propolis extracts (MICs between 16 and 125 microg mL(-1)). The most susceptible species were Microsporum gypseum, Trichophyton mentagrophytes, and Trichophyton rubrum. The main bioactive compounds were 2',4'-dihydroxy-3'-methoxychalcone 2 and 2',4'-dihydroxychalcone 3. Both displayed strong activity against clinical isolates of T. rubrum and T. mentagrophytes (MICs and MFCs between 1.9 and 2.9 microg mL(-1)). Additionally, galangin 5, pinocembrin 6, and 7-hydroxy-8-methoxyflavanone 9 were isolated from propolis samples and Zuccagnia punctata exudates, showing moderate antifungal activity. This is the first study matching the chemical profile of Z. punctata Cav. exudates with their corresponding propolis, giving strong evidence on the botanical origin of the studied propolis.

On the aero-elastic design of the DTU 10MW wind turbine blade for the LIFES50+ wind tunnel scale model

NASA Astrophysics Data System (ADS)

Bayati, I.; Belloli, M.; Bernini, L.; Mikkelsen, R.; Zasso, A.

2016-09-01

This paper illustrates the aero-elastic optimal design, the realization and the verification of the wind tunnel scale model blades for the DTU 10 MW wind turbine model, within LIFES50+ project. The aerodynamic design was focused on the minimization of the difference, in terms of thrust coefficient, with respect to the full scale reference. From the Selig low Reynolds database airfoils, the SD7032 was chosen for this purpose and a proper constant section wing was tested at DTU red wind tunnel, providing force and distributed pressure coefficients for the design, in the Reynolds range 30-250 E3 and for different angles of attack. The aero-elastic design algorithm was set to define the optimal spanwise thickness over chord ratio (t/c), the chord length and the twist to match the first flapwise scaled natural frequency. An aluminium mould for the carbon fibre was CNC manufactured based on B-Splines CAD definition of the external geometry. Then the wind tunnel tests at Politecnico di Milano confirmed successful design and manufacturing approaches.

Integrated approach for stress based lifing of aero gas turbine blades

NASA Astrophysics Data System (ADS)

Abu, Abdullahi Obonyegba

In order to analyse the turbine blade life, the damage due to the combined thermal and mechanical loads should be adequately accounted for. This is more challenging when detailed component geometry is limited. Therefore, a compromise between the level of geometric detail and the complexity of the lifing method to be implemented would be necessary. This research focuses on how the life assessment of aero engine turbine blades can be done, considering the balance between available design inputs and adequate level of fidelity. Accordingly, the thesis contributes to developing a generic turbine blade lifing method that is based on the engine thermodynamic cycle; as well as integrating critical design/technological factors and operational parameters that influence the aero engine blade life. To this end, thermo-mechanical fatigue was identified as the critical damage phenomenon driving the life of the turbine blade.. The developed approach integrates software tools and numerical models created using the minimum design information typically available at the early design stages. Using finite element analysis of an idealised blade geometry, the approach captures relevant impacts of thermal gradients and thermal stresses that contribute to the thermo-mechanical fatigue damage on the gas turbine blade. The blade life is evaluated using the Neu/Sehitoglu thermo-mechanical fatigue model that considers damage accumulation due to fatigue, oxidation, and creep. The leading edge is examined as a critical part of the blade to estimate the damage severity for different design factors and operational parameters. The outputs of the research can be used to better understand how the environment and the operating conditions of the aircraft affect the blade life consumption and therefore what is the impact on the maintenance cost and the availability of the propulsion system. This research also finds that the environmental (oxidation) effect drives the blade life and the blade coolant

Travel modeling in an era of connected and automated transportation systems: an investigation in the Dallas-Fort Worth area.

DOT National Transportation Integrated Search

2017-02-01

The North Central Texas Council of Governments (NCTCOG) engaged D-STOP to conduct a planned four-year study to analyze the status and progress of connected/autonomous vehicle (CAV) development, determine what the wide-ranging effects of the technolog...

Switching LPV Control with Double-Layer LPV Model for Aero-Engines

NASA Astrophysics Data System (ADS)

Tang, Lili; Huang, Jinquan; Pan, Muxuan

2017-11-01

To cover the whole range of operating conditions of aero-engine, a double-layer LPV model is built so as to take into account of the variability due to the flight altitude, Mach number and the rotational speed. With this framework, the problem of designing LPV state-feedback robust controller that guarantees desired bounds on both H_∞ and H_2 performances is considered. Besides this, to reduce the conservativeness caused by a single LPV controller of the whole flight envelope and the common Lyapunov function method, a new method is proposed to design a family of LPV switching controllers. The switching LPV controllers can ensure that the closed-loop system remains stable in the sense of Lyapunov under arbitrary switching logic. Meanwhile, the switching LPV controllers can ensure the parameters change smoothly. The validity and performance of the theoretical results are demonstrated through a numerical example.

Soma size and Cav1.3 channel expression in vulnerable and resistant motoneuron populations of the SOD1G93A mouse model of ALS

PubMed Central

Shoenfeld, Liza; Westenbroek, Ruth E.; Fisher, Erika; Quinlan, Katharina A.; Tysseling, Vicki M.; Powers, Randall K.; Heckman, Charles J.; Binder, Marc D.

2014-01-01

Abstract Although the loss of motoneurons is an undisputed feature of amyotrophic lateral sclerosis (ALS) in man and in its animal models (SOD1 mutant mice), how the disease affects the size and excitability of motoneurons prior to their degeneration is not well understood. This study was designed to test the hypothesis that motoneurons in mutant SOD1G93A mice exhibit an enlargement of soma size (i.e., cross‐sectional area) and an increase in Cav1.3 channel expression at postnatal day 30, well before the manifestation of physiological symptoms that typically occur at p90 (Chiu et al. 1995). We made measurements of spinal and hypoglossal motoneurons vulnerable to degeneration, as well as motoneurons in the oculomotor nucleus that are resistant to degeneration. Overall, we found that the somata of motoneurons in male SOD1G93A mutants were larger than those in wild‐type transgenic males. When females were included in the two groups, significance was lost. Expression levels of the Cav1.3 channels were not differentiated by genotype, sex, or any interaction of the two. These results raise the intriguing possibility of an interaction between male sex steroid hormones and the SOD1 mutation in the etiopathogenesis of ALS. PMID:25107988

Nose-to-tail analysis of an airbreathing hypersonic vehicle using an in-house simplified tool

NASA Astrophysics Data System (ADS)

Piscitelli, Filomena; Cutrone, Luigi; Pezzella, Giuseppe; Roncioni, Pietro; Marini, Marco

2017-07-01

SPREAD (Scramjet PREliminary Aerothermodynamic Design) is a simplified, in-house method developed by CIRA (Italian Aerospace Research Centre), able to provide a preliminary estimation of the performance of engine/aeroshape for airbreathing configurations. It is especially useful for scramjet engines, for which the strong coupling between the aerothermodynamic (external) and propulsive (internal) flow fields requires real-time screening of several engine/aeroshape configurations and the identification of the most promising one/s with respect to user-defined constraints and requirements. The outcome of this tool defines the base-line configuration for further design analyses with more accurate tools, e.g., CFD simulations and wind tunnel testing. SPREAD tool has been used to perform the nose-to-tail analysis of the LAPCAT-II Mach 8 MR2.4 vehicle configuration. The numerical results demonstrate SPREAD capability to quickly predict reliable values of aero-propulsive balance (i.e., net-thrust) and aerodynamic efficiency in a pre-design phase.

KC-135 aero-optical turbulent boundary layer/shear layer experiment revisited

NASA Technical Reports Server (NTRS)

Craig, J.; Allen, C.

1987-01-01

The aero-optical effects associated with propagating a laser beam through both an aircraft turbulent boundary layer and artificially generated shear layers are examined. The data present comparisons from observed optical performance with those inferred from aerodynamic measurements of unsteady density and correlation lengths within the same random flow fields. Using optical instrumentation with tens of microsecond temporal resolution through a finite aperture, optical performance degradation was determined and contrasted with the infinite aperture time averaged aerodynamic measurement. In addition, the optical data were artificially clipped to compare to theoretical scaling calculations. Optical instrumentation consisted of a custom Q switched Nd:Yag double pulsed laser, and a holographic camera which recorded the random flow field in a double pass, double pulse mode. Aerodynamic parameters were measured using hot film anemometer probes and a five hole pressure probe. Each technique is described with its associated theoretical basis for comparison. The effects of finite aperture and spatial and temporal frequencies of the random flow are considered.

A comparative study of mucilage and pulp polysaccharides from tamarillo fruit (Solanum betaceum Cav.).

PubMed

do Nascimento, Georgia Erdmann; Iacomini, Marcello; Cordeiro, Lucimara M C

2016-07-01

A comparative study of mucilage (locular tissue) and pulp polysaccharides from ripe tamarillo fruits (Solanum betaceum Cav.) was carried out. After aqueous and alkaline extractions and various purification steps (freeze-thaw and α-amylase - EC 3.2.1.1 treatments, Fehling precipitation and ultrafiltration through 50 kDa cut-off membrane), the obtained fractions from mucilage were analyzed by sugar composition, HPSEC, and NMR spectroscopy analyses. The results showed that the mucilage of tamarillo contains a highly methoxylated homogalacturonans mixed with type I arabinogalactans, a linear (1 → 5)-linked α-L-arabinan, and a linear (1 → 4)-β-D-xylan. A comparison with polysaccharides extracted from the pulp revealed that differences were observed in the yield and in the ratio of extracted polysaccharides. Moreover, structural differences between pulp and mucilage polysaccharides were also observed, such as in the length of side chains of the pectins, and in the degree of branching of the xylans. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Antifungal activity of Zuccagnia punctata Cav.: evidence for the mechanism of action.

PubMed

Svetaz, Laura; Agüero, María Belén; Alvarez, Sandra; Luna, Lorena; Feresin, Gabriela; Derita, Marcos; Tapia, Alejandro; Zacchino, Susana

2007-08-01

Petroleum ether and dichloromethane extracts of fruits, aerial parts and exudate of Zuccagnia punctata Cav. (Fabaceae) showed moderate antifungal activities against the yeasts C. albicans, S. cerevisiae and C. neoformans (MICs: 62.5 - 250 microg/mL) and very strong antifungal activities against the dermatophytes M. gypseum, T. rubrum and T. mentagrophytes (MICs: 8 - 16 microg/mL) thus supporting the ethnopharmacological use of this plant. Antifungal activity-directed fractionation of active extracts by using bioautography led to the isolation of 2',4'-dihydroxy-3'-methoxychalcone (1) and 2',4'-dihydroxychalcone (2) as the compounds responsible for the antifungal activity. Second-order studies included MIC (80), MIC (50) and MFC of both chalcones in an extended panel of clinical isolates of the most sensitive fungi, and also comprised a series of targeted assays. They showed that the most active chalcone 2 is fungicidal rather than fungistatic, does not disrupt the fungal membranes up to 4 x MFC and does not act by inhibiting the fungal cell wall. So, 2',4'-dihydroxychalcone would act by a different mechanism of action than the antifungal drugs in current clinical use, such as amphotericin B, azoles or echinocandins, and thus appears to be very promising as a novel antifungal agent.

Development of an Aero-Optics Software Library and Integration into Structured Overset and Unstructured Computational Fluid Dynamics (CFD) Flow Solvers

DTIC Science & Technology

2011-04-01

some similarities to the far- field (i.e. atmospheric ) propagation, but due to the interactions between turbulence length scales, beam wavelengths...equivalently, phase differences, have been used to characterize the beam distortion caused by the unsteady turbulent flow field. A Partially-Averaged Navier...A., Wang, M., and Moin, P., “Computational Study of Aero-Optical Distortion by Turbulent Wake,” AIAA Paper 2005-4655. [11] Mani, A., Wang, M., and

Human-Vehicle Interface for Semi-Autonomous Operation of Uninhabited Aero Vehicles

NASA Technical Reports Server (NTRS)

Jones, Henry L.; Frew, Eric W.; Woodley, Bruce R.; Rock, Stephen M.

2001-01-01

The robustness of autonomous robotic systems to unanticipated circumstances is typically insufficient for use in the field. The many skills of human user often fill this gap in robotic capability. To incorporate the human into the system, a useful interaction between man and machine must exist. This interaction should enable useful communication to be exchanged in a natural way between human and robot on a variety of levels. This report describes the current human-robot interaction for the Stanford HUMMINGBIRD autonomous helicopter. In particular, the report discusses the elements of the system that enable multiple levels of communication. An intelligent system agent manages the different inputs given to the helicopter. An advanced user interface gives the user and helicopter a method for exchanging useful information. Using this human-robot interaction, the HUMMINGBIRD has carried out various autonomous search, tracking, and retrieval missions.

Neo-clerodane and abietane diterpenoids with neurotrophic activities from the aerial parts of Salvia leucantha Cav.

PubMed

Li, Lai-Wei; Qi, Yan-Yan; Liu, Shi-Xi; Wu, Xing-De; Zhao, Qin-Shi

2018-04-04

Four new neoclerodane diterpenoids, leucansalvialins FI (1-4), and one rare 18(4 → 3)-abeo-abietane diterpenoid, leucansalvialin J (5), were isolated from the aerial part of Salvia leucantha Cav., along with 14 known analogues. Leucansalvialin F (1) represents the first rearranged salvigenane type clerodane-17,12:18,6-diolide. Their structures were elucidated by 1D and 2D NMR spectroscopic data analysis, and the absolute configurations of 1, 2, 3, and 5 were determinded by X-ray diffraction crystal analysis and the ECD technique. All of the isolated components were evaluated for their neurotrophic activities on PC12 cells and all new compounds were evaluated for their cytotoxicity against five human cancer cell lines (HL-60, A-549, SMMC-7721, MCF-7, and SW480). Compounds 2 and 5 showed moderate neuroprotective effects in an in vitro assay. Copyright © 2018. Published by Elsevier B.V.

Singlet oxygen quenching and radical scavenging capacities of structurally-related flavonoids present in Zuccagnia punctata Cav.

PubMed

Vieyra, Faustino E Morán; Boggetti, Héctor J; Zampini, Iris C; Ordoñez, Roxana M; Isla, María I; Alvarez, Rosa M S; De Rosso, Veridiana; Mercadante, Adriana Z; Borsarelli, Claudio D

2009-06-01

The singlet oxygen (1O2) quenching and free radical (DPPH(*), ABTS(* +) and O2(* -)) scavenging ability of three structurally-related flavonoids (7-hydroxyflavanone HF, 2',4'-dihydroxychalcone DHC and 3,7-dihydroxyflavone DHF) present in the Argentinean native shrub Zuccagnia punctata Cav. were studied in solution by combining electrochemical and kinetic measurements, mass spectroscopy, end-point antioxidant assays and computational calculations. The results showed that the antioxidant properties of these flavonoids depend on several factors, such as their electron- and hydrogen atom donor capacity, the ionization degree of the more acidic group, solvatation effects and electrostatic interactions with the oxidant species. The theoretical calculations for both the gas and solution phases at the B3LYP level of theory for the Osanger reaction field model agreed with the experimental findings, thus supporting the characterization of the antioxidant mechanism of the Z. punctata flavonoids.

Improving Fidelity of Launch Vehicle Liftoff Acoustic Simulations

NASA Technical Reports Server (NTRS)

Liever, Peter; West, Jeff

2016-01-01

Launch vehicles experience high acoustic loads during ignition and liftoff affected by the interaction of rocket plume generated acoustic waves with launch pad structures. Application of highly parallelized Computational Fluid Dynamics (CFD) analysis tools optimized for application on the NAS computer systems such as the Loci/CHEM program now enable simulation of time-accurate, turbulent, multi-species plume formation and interaction with launch pad geometry and capture the generation of acoustic noise at the source regions in the plume shear layers and impingement regions. These CFD solvers are robust in capturing the acoustic fluctuations, but they are too dissipative to accurately resolve the propagation of the acoustic waves throughout the launch environment domain along the vehicle. A hybrid Computational Fluid Dynamics and Computational Aero-Acoustics (CFD/CAA) modeling framework has been developed to improve such liftoff acoustic environment predictions. The framework combines the existing highly-scalable NASA production CFD code, Loci/CHEM, with a high-order accurate discontinuous Galerkin (DG) solver, Loci/THRUST, developed in the same computational framework. Loci/THRUST employs a low dissipation, high-order, unstructured DG method to accurately propagate acoustic waves away from the source regions across large distances. The DG solver is currently capable of solving up to 4th order solutions for non-linear, conservative acoustic field propagation. Higher order boundary conditions are implemented to accurately model the reflection and refraction of acoustic waves on launch pad components. The DG solver accepts generalized unstructured meshes, enabling efficient application of common mesh generation tools for CHEM and THRUST simulations. The DG solution is coupled with the CFD solution at interface boundaries placed near the CFD acoustic source regions. Both simulations are executed simultaneously with coordinated boundary condition data exchange.

Transient compartment-like syndrome and normokalaemic periodic paralysis due to a Cav1.1 mutation

PubMed Central

Fan, Chunxiang; Lehmann-Horn, Frank; Weber, Marc-André; Bednarz, Marcin; Groome, James R.; Jonsson, Malin K. B.

2013-01-01

We studied a two-generation family presenting with conditions that included progressive permanent weakness, myopathic myopathy, exercise-induced contracture before normokalaemic periodic paralysis or, if localized to the tibial anterior muscle group, transient compartment-like syndrome (painful acute oedema with neuronal compression and drop foot). 23Na and 1H magnetic resonance imaging displayed myoplasmic sodium overload, and oedema. We identified a novel familial Cav1.1 calcium channel mutation, R1242G, localized to the third positive charge of the domain IV voltage sensor. Functional expression of R1242G in the muscular dysgenesis mouse cell line GLT revealed a 28% reduced central pore inward current and a −20 mV shift of the steady-state inactivation curve. Both changes may be at least partially explained by an outward omega (gating pore) current at positive potentials. Moreover, this outward omega current of 27.5 nS/nF may cause the reduction of the overshoot by 13 mV and slowing of the upstroke of action potentials by 36% that are associated with muscle hypoexcitability (permanent weakness and myopathic myopathy). In addition to the outward omega current, we identified an inward omega pore current of 95 nS/nF at negative membrane potentials after long depolarizing pulses that shifts the R1242G residue above the omega pore constriction. A simulation reveals that the inward current might depolarize the fibre sufficiently to trigger calcium release in the absence of an action potential and therefore cause an electrically silent depolarization-induced muscle contracture. Additionally, evidence of the inward current can be found in 23Na magnetic resonance imaging-detected sodium accumulation and 1H magnetic resonance imaging-detected oedema. We hypothesize that the episodes are normokalaemic because of depolarization-induced compensatory outward potassium flux through both delayed rectifiers and omega pore. We conclude that the position of the R1242G residue

Using Satellite Observations to Evaluate the AeroCOM Volcanic Emissions Inventory and the Dispersal of Volcanic SO2 Clouds in MERRA

NASA Technical Reports Server (NTRS)

Hughes, Eric J.; Krotkov, Nickolay; da Silva, Arlindo; Colarco, Peter

2015-01-01

Simulation of volcanic emissions in climate models requires information that describes the eruption of the emissions into the atmosphere. While the total amount of gases and aerosols released from a volcanic eruption can be readily estimated from satellite observations, information about the source parameters, like injection altitude, eruption time and duration, is often not directly known. The AeroCOM volcanic emissions inventory provides estimates of eruption source parameters and has been used to initialize volcanic emissions in reanalysis projects, like MERRA. The AeroCOM volcanic emission inventory provides an eruptions daily SO2 flux and plume top altitude, yet an eruption can be very short lived, lasting only a few hours, and emit clouds at multiple altitudes. Case studies comparing the satellite observed dispersal of volcanic SO2 clouds to simulations in MERRA have shown mixed results. Some cases show good agreement with observations Okmok (2008), while for other eruptions the observed initial SO2 mass is half of that in the simulations, Sierra Negra (2005). In other cases, the initial SO2 amount agrees with the observations but shows very different dispersal rates, Soufriere Hills (2006). In the aviation hazards community, deriving accurate source terms is crucial for monitoring and short-term forecasting (24-h) of volcanic clouds. Back trajectory methods have been developed which use satellite observations and transport models to estimate the injection altitude, eruption time, and eruption duration of observed volcanic clouds. These methods can provide eruption timing estimates on a 2-hour temporal resolution and estimate the altitude and depth of a volcanic cloud. To better understand the differences between MERRA simulations and volcanic SO2 observations, back trajectory methods are used to estimate the source term parameters for a few volcanic eruptions and compared to their corresponding entry in the AeroCOM volcanic emission inventory. The nature of

Calmodulin-dependent gating of Ca(v)1.2 calcium channels in the absence of Ca(v)beta subunits.

PubMed

Ravindran, Arippa; Lao, Qi Zong; Harry, Jo Beth; Abrahimi, Parwiz; Kobrinsky, Evgeny; Soldatov, Nikolai M

2008-06-10

It is generally accepted that to generate calcium currents in response to depolarization, Ca(v)1.2 calcium channels require association of the pore-forming alpha(1C) subunit with accessory Ca(v)beta and alpha(2)delta subunits. A single calmodulin (CaM) molecule is tethered to the C-terminal alpha(1C)-LA/IQ region and mediates Ca2+-dependent inactivation of the channel. Ca(v)beta subunits are stably associated with the alpha(1C)-interaction domain site of the cytoplasmic linker between internal repeats I and II and also interact dynamically, in a Ca2+-dependent manner, with the alpha(1C)-IQ region. Here, we describe a surprising discovery that coexpression of exogenous CaM (CaM(ex)) with alpha(1C)/alpha(2)delta in COS1 cells in the absence of Ca(v)beta subunits stimulates the plasma membrane targeting of alpha(1C), facilitates calcium channel gating, and supports Ca2+-dependent inactivation. Neither real-time PCR with primers complementary to monkey Ca(v)beta subunits nor coimmunoprecipitation analysis with exogenous alpha(1C) revealed an induction of endogenous Ca(v)beta subunits that could be linked to the effect of CaM(ex). Coexpression of a calcium-insensitive CaM mutant CaM(1234) also facilitated gating of Ca(v)beta-free Ca(v)1.2 channels but did not support Ca2+-dependent inactivation. Our results show there is a functional matchup between CaM(ex) and Ca(v)beta subunits that, in the absence of Ca(v)beta, renders Ca2+ channel gating facilitated by CaM molecules other than the one tethered to LA/IQ to support Ca2+-dependent inactivation. Thus, coexpression of CaM(ex) creates conditions when the channel gating, voltage- and Ca2+-dependent inactivation, and plasma-membrane targeting occur in the absence of Ca(v)beta. We suggest that CaM(ex) affects specific Ca(v)beta-free conformations of the channel that are not available to endogenous CaM.

Development of a real-time prediction model of driver behavior at intersections using kinematic time series data.

PubMed

Tan, Yaoyuan V; Elliott, Michael R; Flannagan, Carol A C

2017-09-01

As connected autonomous vehicles (CAVs) enter the fleet, there will be a long period when these vehicles will have to interact with human drivers. One of the challenges for CAVs is that human drivers do not communicate their decisions well. Fortunately, the kinematic behavior of a human-driven vehicle may be a good predictor of driver intent within a short time frame. We analyzed the kinematic time series data (e.g., speed) for a set of drivers making left turns at intersections to predict whether the driver would stop before executing the turn. We used principal components analysis (PCA) to generate independent dimensions that explain the variation in vehicle speed before a turn. These dimensions remained relatively consistent throughout the maneuver, allowing us to compute independent scores on these dimensions for different time windows throughout the approach to the intersection. We then linked these PCA scores to whether a driver would stop before executing a left turn using the random intercept Bayesian additive regression trees. Five more road and observable vehicle characteristics were included to enhance prediction. Our model achieved an area under the receiver operating characteristic curve (AUC) of 0.84 at 94m away from the center of an intersection and steadily increased to 0.90 by 46m away from the center of an intersection. Copyright © 2017 Elsevier Ltd. All rights reserved.

PCB 126 toxicity is modulated by cross-talk between caveolae and Nrf2 signaling

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

Petriello, Michael C.; University of Kentucky Superfund Research Center, Lexington, KY 40536; Han, Sung Gu

2014-06-01

Environmental toxicants such as polychlorinated biphenyls (PCBs) have been implicated in the promotion of multiple inflammatory disorders including cardiovascular disease, but information regarding mechanisms of toxicity and cross-talk between relevant cell signaling pathways is lacking. To examine the hypothesis that cross-talk between membrane domains called caveolae and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathways alters PCB-induced inflammation, caveolin-1 was silenced in vascular endothelial cells, resulting in a decreased PCB-induced inflammatory response. Cav-1 silencing (siRNA treatment) also increased levels of Nrf2-ARE transcriptional binding, resulting in higher mRNA levels of the antioxidant genes glutathione s-transferase and NADPH dehydrogenase quinone-1 in both vehiclemore » and PCB-treated systems. Along with this upregulated antioxidant response, Cav-1 siRNA treated cells exhibited decreased mRNA levels of the Nrf2 inhibitory protein Keap1 in both vehicle and PCB-treated samples. Silencing Cav-1 also decreased protein levels of Nrf2 inhibitory proteins Keap1 and Fyn kinase, especially in PCB-treated cells. Further, endothelial cells from wildtype and Cav-1 −/− mice were isolated and treated with PCB to better elucidate the role of functional caveolae in PCB-induced endothelial inflammation. Cav-1 −/− endothelial cells were protected from PCB-induced cellular dysfunction as evidenced by decreased vascular cell adhesion molecule (VCAM-1) protein induction. Compared to wildtype cells, Cav-1 −/− endothelial cells also allowed for a more effective antioxidant response, as observed by higher levels of the antioxidant genes. These data demonstrate novel cross-talk mechanisms between Cav-1 and Nrf2 and implicate the reduction of Cav-1 as a protective mechanism for PCB-induced cellular dysfunction and inflammation. - Highlights: • Reduction of caveolin-1 protein protects against polychlorinated biphenyl toxicity. �

A Viral Receptor Complementation Strategy to Overcome CAV-2 Tropism for Efficient Retrograde Targeting of Neurons.

PubMed

Li, Shu-Jing; Vaughan, Alexander; Sturgill, James Fitzhugh; Kepecs, Adam

2018-06-06

Retrogradely transported neurotropic viruses enable genetic access to neurons based on their long-range projections and have become indispensable tools for linking neural connectivity with function. A major limitation of viral techniques is that they rely on cell-type-specific molecules for uptake and transport. Consequently, viruses fail to infect variable subsets of neurons depending on the complement of surface receptors expressed (viral tropism). We report a receptor complementation strategy to overcome this by potentiating neurons for the infection of the virus of interest-in this case, canine adenovirus type-2 (CAV-2). We designed AAV vectors for expressing the coxsackievirus and adenovirus receptor (CAR) throughout candidate projection neurons. CAR expression greatly increased retrograde-labeling rates, which we demonstrate for several long-range projections, including some resistant to other retrograde-labeling techniques. Our results demonstrate a receptor complementation strategy to abrogate endogenous viral tropism and thereby facilitate efficient retrograde targeting for functional analysis of neural circuits. Copyright © 2018 Elsevier Inc. All rights reserved.

A new method for the estimation of high temperature radiant heat emittance by means of aero-acoustic levitation

NASA Astrophysics Data System (ADS)

Greffrath, Fabian; Prieler, Robert; Telle, Rainer

2014-11-01

A new method for the experimental estimation of radiant heat emittance at high temperatures has been developed which involves aero-acoustic levitation of samples, laser heating and contactless temperature measurement. Radiant heat emittance values are determined from the time dependent development of the sample temperature which requires analysis of both the radiant and convective heat transfer towards the surroundings by means of fluid dynamics calculations. First results for the emittance of a corundum sample obtained with this method are presented in this article and found in good agreement with literature values.

Blades Forced Vibration Under Aero-Elastic Excitation Modeled by Van der Pol

NASA Astrophysics Data System (ADS)

Pust, Ladislav; Pesek, Ludek

This paper employs a new analytical approach to model the influence of aerodynamic excitation on the dynamics of a bladed cascade at the flutter state. The flutter is an aero-elastic phenomenon that is linked to the interaction of the flow and the traveling deformation wave in the cascade when only the damping of the cascade changes. As a case study the dynamic properties of the five-blade-bunch excited by the running harmonic external forces and aerodynamic self-excited forces are investigated. This blade-bunch is linked in the shroud by means of the viscous-elastic damping elements. The external running excitation depends on the ratio of stator and rotor blade numbers and corresponds to the real type of excitation in the steam turbine. The aerodynamic self-excited forces are modeled by two types of Van der Pol nonlinear models. The influence of the interaction of both types of self-excitation with the external running excitation is investigated on the response curves.

A Recurrent Mutation in CACNA1G Alters Cav3.1 T-Type Calcium-Channel Conduction and Causes Autosomal-Dominant Cerebellar Ataxia

PubMed Central

Coutelier, Marie; Blesneac, Iulia; Monteil, Arnaud; Monin, Marie-Lorraine; Ando, Kunie; Mundwiller, Emeline; Brusco, Alfredo; Le Ber, Isabelle; Anheim, Mathieu; Castrioto, Anna; Duyckaerts, Charles; Brice, Alexis; Durr, Alexandra; Lory, Philippe; Stevanin, Giovanni

2015-01-01

Hereditary cerebellar ataxias (CAs) are neurodegenerative disorders clinically characterized by a cerebellar syndrome, often accompanied by other neurological or non-neurological signs. All transmission modes have been described. In autosomal-dominant CA (ADCA), mutations in more than 30 genes are implicated, but the molecular diagnosis remains unknown in about 40% of cases. Implication of ion channels has long been an ongoing topic in the genetics of CA, and mutations in several channel genes have been recently connected to ADCA. In a large family affected by ADCA and mild pyramidal signs, we searched for the causative variant by combining linkage analysis and whole-exome sequencing. In CACNA1G, we identified a c.5144G>A mutation, causing an arginine-to-histidine (p.Arg1715His) change in the voltage sensor S4 segment of the T-type channel protein Cav3.1. Two out of 479 index subjects screened subsequently harbored the same mutation. We performed electrophysiological experiments in HEK293T cells to compare the properties of the p.Arg1715His and wild-type Cav3.1 channels. The current-voltage and the steady-state activation curves of the p.Arg1715His channel were shifted positively, whereas the inactivation curve had a higher slope factor. Computer modeling in deep cerebellar nuclei (DCN) neurons suggested that the mutation results in decreased neuronal excitability. Taken together, these data establish CACNA1G, which is highly expressed in the cerebellum, as a gene whose mutations can cause ADCA. This is consistent with the neuropathological examination, which showed severe Purkinje cell loss. Our study further extends our knowledge of the link between calcium channelopathies and CAs. PMID:26456284

Aero-acoustic performance comparison of core engine noise suppressors on NASA quiet engine C

NASA Technical Reports Server (NTRS)

Bloomer, H. E.; Schaefer, J. W.

1977-01-01

The relative aero-acoustic effectiveness of two core engine suppressors, a contractor-designed suppressor delivered with the Quiet Engine, and a NASA-designed suppressor was evaluated. The NASA suppressor was tested with and without a splitter making a total of three configurations being reported in addition to the baseline hardwall case. The aerodynamic results are presented in terms of tailpipe pressure loss, corrected net thrust, and corrected specific fuel consumption as functions of engine power setting. The acoustic results are divided into duct and far-field acoustic data. The NASA-designed core suppressor did the better job of suppressing aft end noise, but the splitter associated with it caused a significant engine performance penality. The NASA core suppressor without the spltter suppressed most of the core noise without any engine performance penalty.

A Summary of the Slush Hydrogen Technology Program for the National Aero-Space Plane

NASA Technical Reports Server (NTRS)

Mcnelis, Nancy B.; Hardy, Terry L.; Whalen, Margaret V.; Kudlac, Maureen T.; Moran, Matthew E.; Tomsik, Thomas M.; Haberbusch, Mark S.

1995-01-01

Slush hydrogen, a mixture of solid and liquid hydrogen, offers advantages of higher density (16 percent) and higher heat capacity (18 percent) than normal boiling point hydrogen. The combination of increased density and heat capacity of slush hydrogen provided a potential to decrease the gross takeoff weight of the National Aero-Space Plane (NASP) and therefore slush hydrogen was selected as the propellant. However, no large-scale data was available on the production, transfer and tank pressure control characteristics required to use slush hydrogen as a fuel. Extensive testing has been performed at the NASA Lewis Research Center K-Site and Small Scale Hydrogen Test Facility between 1990 and the present to provide a database for the use of slush hydrogen. This paper summarizes the results of this testing.

Chemical composition and antifungal activity of the essential oils of Lavandula pedunculata (Miller) Cav.

PubMed

Zuzarte, Monica; Gonçalves, Maria J; Cavaleiro, Carlos; Dinis, Augusto M; Canhoto, Jorge M; Salgueiro, Lígia R

2009-08-01

The chemical composition and antifungal activity of the essential oils of Lavandula pedunculata (Miller) Cav., harvested in North and Central Portugal, were investigated. The essential oils were isolated by hydrodistillation and analyzed by GC and GC/MS. The minimal-inhibitory concentration (MIC) and the minimal-lethal concentration (MLC) of the essential oils and of their major constituents were used to evaluate the antifungal activity against different strains of fungi involved in candidosis, dematophytosis, and aspergillosis. The oils were characterized by a high percentage of oxygenated monoterpenes, the main compounds being 1,8-cineole (2.4-55.5%), fenchone (1.3-59.7%), and camphor (3.6-48.0%). Statistical analysis differentiated the essential oils into two main types, one characterized by the predominance of fenchone and the other one by the predominance of 1,8-cineole. Within the 1,8-cineole chemotype, two subgroups were well-defined taking into account the percentages of camphor. A significant antifungal activity of the oils was found against dermatophyte strains. The essential oil with the highest content of camphor was the most active with MIC and MLC values ranging from 0.32-0.64 microl/ml.

A Fast Proceduere for Optimizing Thermal Protection Systems of Re-Entry Vehicles

NASA Astrophysics Data System (ADS)

Ferraiuolo, M.; Riccio, A.; Tescione, D.; Gigliotti, M.

The aim of the present work is to introduce a fast procedure to optimize thermal protection systems for re-entry vehicles subjected to high thermal loads. A simplified one-dimensional optimization process, performed in order to find the optimum design variables (lengths, sections etc.), is the first step of the proposed design procedure. Simultaneously, the most suitable materials able to sustain high temperatures and meeting the weight requirements are selected and positioned within the design layout. In this stage of the design procedure, simplified (generalized plane strain) FEM models are used when boundary and geometrical conditions allow the reduction of the degrees of freedom. Those simplified local FEM models can be useful because they are time-saving and very simple to build; they are essentially one dimensional and can be used for optimization processes in order to determine the optimum configuration with regard to weight, temperature and stresses. A triple-layer and a double-layer body, subjected to the same aero-thermal loads, have been optimized to minimize the overall weight. Full two and three-dimensional analyses are performed in order to validate those simplified models. Thermal-structural analyses and optimizations are executed by adopting the Ansys FEM code.

Evaluation of the aerosol vertical distribution in global aerosol models through comparison against CALIOP measurements: AeroCom phase II results: AEROSOL PROFILES IN AEROCOM II GCM

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

Koffi, Brigitte; Schulz, Michael; Bréon, François-Marie

2016-06-27

The ability of eleven models in simulating the aerosol vertical distribution from regional to global scales, as part of the second phase of the AeroCom model inter-comparison initiative (AeroCom II) is assessed and compared to results of the first phase. The evaluation is performed using a global monthly gridded dataset of aerosol extinction profiles built on purpose from the CALIOP (Cloud-Aerosol Lidar with Orthogonal Polarization) Layer Product 3.01. Results over 12 sub-continental regions show that five models improved whereas three degraded in reproducing the Zα 0-6 km mean extinction height diagnostic, which is computed over the 0-6 km altitude rangemore » for each studied region and season. While the models’ performance remains highly variable, it has generally improved in terms of inter-regional diversity and seasonality. The biases in Zα 0-6 km have notably decreased in the U.S. and European industrial and downwind maritime regions, whereas the timing of the Zα 0-6 km peak season has improved for all but two models. However, most of the models now show a Zα 0-6 km underestimation over land, notably in the dust and biomass burning regions in Asia and Africa. At global scale, the AeroCom II models better reproduce the Zα 0-6 km latitudinal variability over ocean than over land. Hypotheses for the (changes in the) the performance of the individual models and for the inter-model diversity are discussed. We also provide an analysis of the CALIOP limitations and uncertainties that can contribute to the differences between the simulations and observations.« less

Intermediate Experimental Vehicle, ESA Program IXV ATDB Tool and Aerothermodynamic Characterization

NASA Astrophysics Data System (ADS)

Mareschi, Vincenzo; Ferrarella, Daniela; Zaccagnino, Elio; Tribot, Jean-Pierre; Vallee, Jean-Jacques; Haya-Ramos, Rodrigo; Rufolo, Giuseppe; Mancuso, Salvatore

2011-05-01

In the complex domain of the space technologies and among the different applications available in Europe, a great interest has been placed since several years in the development of re-entry technologies. Among the different achievements obtained in that field it is to be recalled the experience of the Atmospheric Re-entry Vehicle flight in 1998 and a certain number of important investments per-formed at Agency and national levels like Hermes, MSTP, Festip, X-38, FLPP, TRP, GSTP, HSTS, AREV, Pre-X. IXV (Intermediate eXperimental V ehicle) builds on these past experiences and studies and it is conceived to be the next technological step forward with respect to ARD With respect to previous European ballistic or quasi- ballistic demonstrators, IXV will have an increased in- flight manoeuvrability and the planned mission will allow verifying the performances of the required technologies against a wider re-entry corridor. This will imply from the pure technological aspect to increase the level of engagement on critical technologies and disciplines like aerodynamics/aerothermodynamics, guidance, navigation, control, thermal protection materials and in flight measurements. In order to support the TPS design and the other sub- systems, an AeroThermodynamicDataBase Tool has been developed by Dassault Aviation and integrated by Thales Alenia Space with the Functional Engineering Simulator (used for GNC performances evaluation) in order to characterize the aerothermodynamic behaviour of the vehicle. This paper will describe: - The methodology used to develop the ATDB tool, based on the processing of CFD computations and WTT campaigns results. - The utilization of the ATDB tool, by means of its integration into the System process. - The methodology used for the aerothermal characterization of IXV.

A review of the in vitro and in vivo valved holding chamber (VHC) literature with a focus on the AeroChamber Plus Flow-Vu Anti-static VHC

PubMed Central

Dissanayake, Sanjeeva; Suggett, Jason

2018-01-01

Valved holding chambers (VHCs) reduce the need for inhalation-actuation coordination with pressurized metered dose inhalers (pMDIs), reduce oropharyngeal drug deposition and may improve lung deposition and clinical outcomes compared to pMDIs used alone. While VHCs are thus widely advocated for use in vulnerable patient groups within clinical and regulatory guidelines, there is less consensus as to whether the performance differences between different VHCs have clinical implications. This review evaluates the VHC literature, in particular the data pertaining to large- versus small-volume chambers, aerosol performance with a VHC adjunct versus a pMDI alone, charge dissipative/conducting versus non-conducting VHCs, and facemasks, to ascertain whether potentially meaningful differences between VHCs exist. Inconsistencies in the literature are examined and explained, and relationships between in vitro and in vivo data are discussed. A particular focus of this review is the AeroChamber Plus® Flow-Vu® Anti-static VHC, the most recent iteration of the AeroChamber VHC family. PMID:29378477

Intelligent behaviors through vehicle-to-vehicle and vehicle-to-infrastructure communication

NASA Astrophysics Data System (ADS)

Garcia, Richard D.; Sturgeon, Purser; Brown, Mike

2012-06-01

The last decade has seen a significant increase in intelligent safety devices on private automobiles. These devices have both increased and augmented the situational awareness of the driver and in some cases provided automated vehicle responses. To date almost all intelligent safety devices have relied on data directly perceived by the vehicle. This constraint has a direct impact on the types of solutions available to the vehicle. In an effort to improve the safety options available to a vehicle, numerous research laboratories and government agencies are investing time and resources into connecting vehicles to each other and to infrastructure-based devices. This work details several efforts in both the commercial vehicle and the private auto industries to increase vehicle safety and driver situational awareness through vehicle-to-vehicle and vehicle-to-infrastructure communication. It will specifically discuss intelligent behaviors being designed to automatically disable non-compliant vehicles, warn tractor trailer vehicles of unsafe lane maneuvers such as lane changes, passing, and merging, and alert drivers to non-line-of-sight emergencies.

Contributions of TetrUSS to Project Orion

NASA Technical Reports Server (NTRS)

Mcmillin, Susan N.; Frink, Neal T.; Kerimo, Johannes; Ding, Djiang; Nayani, Sudheer; Parlette, Edward B.

2011-01-01

The NASA Constellation program has relied heavily on Computational Fluid Dynamics simulations for generating aerodynamic databases and design loads. The Orion Project focuses on the Orion Crew Module and the Orion Launch Abort Vehicle. NASA TetrUSS codes (GridTool/VGRID/USM3D) have been applied in a supporting role to the Crew Exploration Vehicle Aerosciences Project for investigating various aerodynamic sensitivities and supplementing the aerodynamic database. This paper provides an overview of the contributions from the TetrUSS team to the Project Orion Crew Module and Launch Abort Vehicle aerodynamics, along with selected examples to highlight the challenges encountered along the way. A brief description of geometries and tasks will be discussed followed by a description of the flow solution process that produced production level computational solutions. Four tasks conducted by the USM3D team will be discussed to show how USM3D provided aerodynamic data for inclusion in the Orion aero-database, contributed data for the build-up of aerodynamic uncertainties for the aero-database, and provided insight into the flow features about the Crew Module and the Launch Abort Vehicle.

Interactions between N and C termini of α1C subunit regulate inactivation of CaV1.2 L-type Ca2+ channel

PubMed Central

Benmocha Guggenheimer, Adva; Almagor, Lior; Tsemakhovich, Vladimir; Tripathy, Debi Ranjan; Hirsch, Joel A; Dascal, Nathan

2016-01-01

The modulation and regulation of voltage-gated Ca2+ channels is affected by the pore-forming segments, the cytosolic parts of the channel, and interacting intracellular proteins. In this study we demonstrate a direct physical interaction between the N terminus (NT) and C terminus (CT) of the main subunit of the L-type Ca2+ channel CaV1.2, α1C, and explore the importance of this interaction for the regulation of the channel. We used biochemistry to measure the strength of the interaction and to map the location of the interaction sites, and electrophysiology to investigate the functional impact of the interaction. We show that the full-length NT (amino acids 1-154) and the proximal (close to the plasma membrane) part of the CT, pCT (amino acids 1508-1669) interact with sub-micromolar to low-micromolar affinity. Calmodulin (CaM) is not essential for the binding. The results further suggest that the NT-CT interaction regulates the channel's inactivation, and that Ca2+, presumably through binding to calmodulin (CaM), reduces the strength of NT-CT interaction. We propose a molecular mechanism in which NT and CT of the channel serve as levers whose movements regulate inactivation by promoting changes in the transmembrane core of the channel via S1 (NT) or S6 (pCT) segments of domains I and IV, accordingly, and not as a kind of pore blocker. We hypothesize that Ca2+-CaM-induced changes in NT-CT interaction may, in part, underlie the acceleration of CaV1.2 inactivation induced by Ca2+ entry into the cell. PMID:26577286

Thermal Protection for Mars Sample Return Earth Entry Vehicle: A Grand Challenge for Design Methodology and Reliability Verification

NASA Technical Reports Server (NTRS)

Venkatapathy, Ethiraj; Gage, Peter; Wright, Michael J.

2017-01-01

Mars Sample Return is our Grand Challenge for the coming decade. TPS (Thermal Protection System) nominal performance is not the key challenge. The main difficulty for designers is the need to verify unprecedented reliability for the entry system: current guidelines for prevention of backward contamination require that the probability of spores larger than 1 micron diameter escaping into the Earth environment be lower than 1 million for the entire system, and the allocation to TPS would be more stringent than that. For reference, the reliability allocation for Orion TPS is closer to 11000, and the demonstrated reliability for previous human Earth return systems was closer to 1100. Improving reliability by more than 3 orders of magnitude is a grand challenge indeed. The TPS community must embrace the possibility of new architectures that are focused on reliability above thermal performance and mass efficiency. MSR (Mars Sample Return) EEV (Earth Entry Vehicle) will be hit with MMOD (Micrometeoroid and Orbital Debris) prior to reentry. A chute-less aero-shell design which allows for self-righting shape was baselined in prior MSR studies, with the assumption that a passive system will maximize EEV robustness. Hence the aero-shell along with the TPS has to take ground impact and not break apart. System verification will require testing to establish ablative performance and thermal failure but also testing of damage from MMOD, and structural performance at ground impact. Mission requirements will demand analysis, testing and verification that are focused on establishing reliability of the design. In this proposed talk, we will focus on the grand challenge of MSR EEV TPS and the need for innovative approaches to address challenges in modeling, testing, manufacturing and verification.

Potentials for Platooning in U.S. Highway Freight Transport: Preprint

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

Muratori, Matteo; Holden, Jacob; Lammert, Michael

2017-03-15

Smart technologies enabling connection among vehicles and between vehicles and infrastructure as well as vehicle automation to assist human operators are receiving significant attention as means for improving road transportation systems by reducing fuel consumption - and related emissions - while also providing additional benefits through improving overall traffic safety and efficiency. For truck applications, currently responsible for nearly three-quarters of the total U.S. freight energy use and greenhouse gas (GHG) emissions, platooning has been identified as an early feature for connected and automated vehicles (CAVs) that could provide significant fuel savings and improved traffic safety and efficiency without radicalmore » design or technology changes compared to existing vehicles. A statistical analysis was performed based on a large collection of real-world U.S. truck usage data to estimate the fraction of total miles that are technically suitable for platooning. In particular, our analysis focuses on estimating 'platoonable' mileage based on overall highway vehicle use and prolonged high-velocity traveling, establishing that about 65% of the total miles driven by combination trucks could be driven in platoon formation, leading to a 4% reduction in total truck fuel consumption. This technical potential for 'platoonable' miles in the U.S. provides an upper bound for scenario analysis considering fleet willingness to platoon as an estimate of overall benefits of early adoption of CAV technologies. A benefit analysis is proposed to assess the overall potential for energy savings and emissions mitigation by widespread implementation of highway platooning for trucks.« less

Department of Defense Extract of the Budget of the United States Government for Fiscal Years 1992 and 1993

DTIC Science & Technology

1991-02-04

speed rail transport and form effort, the budget gives special emphasis electric battery technology, to high perform - to increased investment in child...in vehicle performance and ca- pabilities. Research efforts have been ex- panded in high -payoff areas associated with a broad range of future vehicle...applications including subsonic and high - speed transport aircraft. The budget proposes $543 million for aero- nautics R&D (excluding High Performance

Techno-functional properties and in vitro bile acid-binding capacities of tamarillo (Solanum betaceum Cav.) hydrocolloids.

PubMed

Gannasin, Sri Puvanesvari; Adzahan, Noranizan Mohd; Mustafa, Shuhaimi; Muhammad, Kharidah

2016-04-01

Hydrocolloids were extracted from seed mucilage and the pulp fractions from red tamarillo (Solanum betaceum Cav.) mesocarp, and characterisation of their techno-functional properties and in vitro bile acid-binding capacities was performed. The seed mucilage hydrocolloids that were extracted, using either 1% citric acid (THC) or water (THW), had a good foaming capacity (32-36%), whereas the pulp hydrocolloids that were extracted, using 72% ethanol (THE) or 20mM HEPES buffer (THH), had no foaming capacity. The pulp hydrocolloid, however, possessed high oil-holding and water-holding capacities in the range of 3.3-3.6 g oil/g dry sample and 25-27 g water/g dry sample, respectively. This enabled the pulp hydrocolloid to entrap more bile acids (35-38% at a hydrocolloid concentration of 2%) in its gelatinous network in comparison to commercial oat fibre and other hydrocolloids studied. The exceptional emulsifying properties (80-96%) of both hydrocolloids suggest their potential applications as food emulsifiers and bile acid binders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparison of aerosol optical properties above clouds between POLDER and AeroCom models over the South East Atlantic Ocean during the fire season: POLDER/AeroCom Comparison Above Clouds

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

Peers, F.; Bellouin, N.; Waquet, F.

Aerosol properties above clouds have been retrieved over the South East Atlantic Ocean during the fire season 2006 using satellite observations from POLDER (Polarization and Directionality of Earth Reflectances). From June to October, POLDER has observed a mean Above-Cloud Aerosol Optical Thickness (ACAOT) of 0.28 and a mean Above-Clouds Single Scattering Albedo (ACSSA) of 0.87 at 550nm. These results have been used to evaluate the simulation of aerosols above clouds in 5 AeroCom (Aerosol Comparisons between Observations and Models) models (GOCART, HadGEM3, ECHAM5-HAM2, OsloCTM2 and SPRINTARS). Most models do not reproduce the observed large aerosol load episodes. The comparison highlightsmore » the importance of the injection height and the vertical transport parameterizations to simulate the large ACAOT observed by POLDER. Furthermore, some models overestimate the ACSSA. In accordance with recent recommendations of the black carbon refractive index, a higher prescription of the imaginary part allows a better comparison with POLDER’s ACSSA.« less

Profiling the array of Ca(v)3.1 variants from the human T-type calcium channel gene CACNA1G: alternative structures, developmental expression, and biophysical variations.

PubMed

Emerick, Mark C; Stein, Rebecca; Kunze, Robin; McNulty, Megan M; Regan, Melissa R; Hanck, Dorothy A; Agnew, William S

2006-08-01

We describe the regulated transcriptome of CACNA1G, a human gene for T-type Ca(v)3.1 calcium channels that is subject to extensive alternative RNA splicing. Fifteen sites of transcript variation include 2 alternative 5'-UTR promoter sites, 2 alternative 3'-UTR polyadenylation sites, and 11 sites of alternative splicing within the open reading frame. A survey of 1580 fetal and adult human brain full-length complementary DNAs reveals a family of 30 distinct transcripts, including multiple functional forms that vary in expression with development. Statistical analyses of fetal and adult transcript populations reveal patterns of linkages among intramolecular splice site configurations that change dramatically with development. A shift from nearly independent, biased splicing in fetal transcripts to strongly concerted splicing in adult transcripts suggests progressive activation of multiple "programs" of splicing regulation that reorganize molecular structures in differentiating cells. Patch-clamp studies of nine selected variants help relate splicing regulation to permutations of the gating parameters most likely to modify T-channel physiology in expressing neurons. Gating behavior reflects combinatorial interactions between variable domains so that molecular phenotype depends on ensembles of coselected domains, consistent with the observed emergence of concerted splicing during development. We conclude that the structural gene and networks of splicing regulatory factors define an integrated system for the phenotypic variation of Ca(v)3.1 biophysics during nervous system development. Copyright 2006 Wiley-Liss, Inc.

Smoking and the risk of upper aero digestive tract cancers for men and women in the Asia-Pacific region.

PubMed

Ansary-Moghaddam, Alireza; Martiniuk, Alexandra; Lam, Tai-Hing; Jamrozik, Konrad; Tamakoshi, Akiko; Fang, Xianghua; Suh, Il; Barzi, Federica; Huxley, Rachel; Woodward, Mark

2009-04-01

Although smoking is an established causal factor for upper aero digestive tract cancer (UADTC), most of the evidence originates from the West. Thus, we analysed data from 455,409 subjects in the Asia Pacific Cohort Studies Collaboration. Over a median of around six years follow-up, 371 deaths from UADTC were observed. The hazard ratio (95% confidence interval) for current smokers, compared with those who had never smoked, was 2.36 (1.76 - 3.16), adjusted for age and alcohol drinking. Tobacco control policies are urgently required in Asia to prevent millions of deaths from UADTC that smoking will otherwise cause.

Blocking the L-type Ca2+ channel (Cav 1.2) is the key mechanism for the vascular relaxing effect of Pterodon spp. and its isolated diterpene methyl-6α-acetoxy-7β-hydroxyvouacapan-17β-oate.

PubMed

de Fátima Reis, Carolina; de Andrade, Daniela Medeiros Lobo; Junior Neves, Bruno; de Almeida Ribeiro Oliveira, Leandra; Pinho, José Felippe; da Silva, Leidiane Pinha; Dos Santos Cruz, Jader; Bara, Maria Teresa Freitas; Andrade, Carolina Horta; Rocha, Matheus Lavorenti

2015-10-01

Pterodon spp. Vogel (Fabaceae), popularly known as "sucupira", has ethnopharmacological application which is described as having antispasmodic and relaxant effects. Hence, it was hypothesized that sucupira oil-resin (SOR) could induce smooth muscle relaxation. So, this study investigated the mechanisms involved in the vasorelaxant effect of SOR and its isolated diterpene (methyl-6α-acetoxy-7β-hydroxyvouacapan-17β-oate). Vascular reactivity experiments were performed using rat aortic rings (n=5-8) with (E+) or without endothelium (E-) in an isolated bath organ. The SOR (0-56 μg/mL) relaxed phenylephrine (E+: 86.7±7.1%; E-: 92.3±4.7%) and KCl contracted rings (E-: 97.1±2.8%). In the same way, diterpene (0-48 μg/mL) also relaxed phenylephrine (E+: 94.5±3.6%; E-: 92.2±3.4%) and KCl contracted rings (E-: 99.7±0.2%). The pre-incubation of arterial rings with cyclopiazonic acid (reticular Ca2+-ATPase inhibitor), tetraethylammonium (K+ channels blocker) or MDL-12,330A (adenylyl cyclesinhibitor) did not modify either SOR- or diterpeneinduced vasorelaxation. However, ODQ (guanylyl cyclase inhibitor) impaired only diterpene-induced vasorelaxation. SOR and diterpene significantly reduced CaCl2-induced contraction stimulated by Bay K8644 (1 μM), phenylephrine (0.1 μM) or KCl solution (40 mM). Computational molecular docking studies demonstrated that the vasodilator effect of diterpene relies on blocking the Cav 1.2 channel, and patch clamp results showed that diterpene substantially decreased the ionic current through Cav 1.2 in freshly dissociated vascular smooth muscle cells. These findings suggest that SOR and its isolated diterpene induce endothelium-independent vascular relaxation by blocking the L-type Ca2+ channel (Cav 1.2). Copyright © 2015 Elsevier Ltd. All rights reserved.

Aero-acoustic performance comparison of core engine noise suppressors on NASA quiet engine 'C'

NASA Technical Reports Server (NTRS)

Bloomer, H. E.; Schaefer, J. W.

1977-01-01

The purpose of the experimental program reported herein was to evaluate and compare the relative aero-acoustic effectiveness of two core engine suppressors, a contractor-designed suppressor delivered with the Quiet Engine, and a NASA-designed suppressor, designed and built subsequently. The NASA suppressor was tested with and without a splitter making a total of three configurations being reported in addition to the baseline hardwall case. The aerodynamic results are presented in terms of tailpipe pressure loss, corrected net thrust, and corrected specific fuel consumption as functions of engine power setting. The acoustic results are divided into duct and far-field acoustic data. The NASA-designed core suppressor did the better job of suppressing aft end noise, but the splitter associated with it caused a significant engine performance penalty. The NASA core suppressor without the splitter suppressed most of the core noise without any engine performance penalty.

The effects of plantar flexor static stretching and dynamic stretching using an aero-step on foot pressure during gait in healthy adults: a preliminary study.

PubMed

Shim, Je-Myung; Jung, Ju-Hyeon; Kim, Hwan-Hee

2015-07-01

[Purpose] The aim of this study was to examine whether plantar flexor static stretching and dynamic stretching using an Aero-Step results in changes in foot pressure during gait in healthy adults. [Subjects] Eighteen normal adults were randomly allocated to either a dynamic stretching using an Aero-Step group (DSUAS) group (n = 8) or a static stretching (SS) group (n = 10). [Methods] The DSUAS and SS participants took part in an exercise program for 15 minutes. Outcome measures were foot plantar pressure, which was measured during the subject's gait stance phase; the asymmetric ratio of foot pressure for both feet; and the visual analogue scale (VAS) measured during the interventions. [Results] There were significant differences in the asymmetric ratio of foot pressure for both feet and VAS between the two groups after intervention. However, there were no significant differences in foot plantar pressure during the gait stance phase within both groups. [Conclusion] DSUSAS is an effective stretching method, as pain during it is lower than that with SS, which can minimize the asymmetric ratio of foot pressure for both feet during gait due to asymmetric postural alignment.

ARES I-X: The First Test Flight of a New Era

NASA Technical Reports Server (NTRS)

Smith, R. Marshall; Davis, Stephan R.; Bryant, Richard Barry; Cook, Steve

2010-01-01

On October 28th, 2009, the National Aeronautics and Space Administration (NASA) launched the Ares I-X Flight Test Vehicle (FTV) from pad 39B, providing the first set of flight test data for NASA's Ares I vehicle design team. This test was critical in providing insight into areas were significant design challenges existed. This paper discusses the objectives of the mission and how they were satisfied. It discusses the overall results of the flight test and look at the data retrieved from the flight. Ares I-X was highly instrumented with over 700 channels of Developmental Flight Instrumentation (DFI). Significant insight was gained in the areas of thrust oscillation, vibro-acoustics, predicting jet interactions and slag ejection from solid rocket systems with submerged nozzles. The paper outlines results from the Guidance Navigation & Control (GN&C), Thermal, Vibro-acoustic, Structures, Aero, Aero-Acoustic and Trajectory teams.

Advances in SiC/SiC Composites for Aero-Propulsion

NASA Technical Reports Server (NTRS)

DiCarlo, James A.

2013-01-01

In the last decade, considerable progress has been made in the development and application of ceramic matrix composites consisting of silicon carbide (SiC) based matrices reinforced by small-diameter continuous-length SiC-based fibers. For example, these SiC/SiC composites are now in the early stages of implementation into hot-section components of civil aero-propulsion gas turbine engines, where in comparison to current metallic components they offer multiple advantages due to their lighter weight and higher temperature structural capability. For current production-ready SiC/SiC, this temperature capability for long time structural applications is 1250 degC, which is better than 1100 degC for the best metallic superalloys. Foreseeing that even higher structural reliability and temperature capability would continue to increase the advantages of SiC/SiC composites, progress in recent years has also been made at NASA toward improving the properties of SiC/SiC composites by optimizing the various constituent materials and geometries within composite microstructures. The primary objective of this chapter is to detail this latter progress, both fundamentally and practically, with particular emphasis on recent advancements in the materials and processes for the fiber, fiber coating, fiber architecture, and matrix, and in the design methods for incorporating these constituents into SiC/SiC microstructures with improved thermo-structural performance.

Mutated CaV2.1 channels dysregulate CASK/P2X3 signaling in mouse trigeminal sensory neurons of R192Q Cacna1a knock-in mice.

PubMed

Gnanasekaran, Aswini; Bele, Tanja; Hullugundi, Swathi; Simonetti, Manuela; Ferrari, Michael D; van den Maagdenberg, Arn M J M; Nistri, Andrea; Fabbretti, Elsa

2013-12-02

ATP-gated P2X3 receptors of sensory ganglion neurons are important transducers of pain as they adapt their expression and function in response to acute and chronic nociceptive signals. The present study investigated the role of calcium/calmodulin-dependent serine protein kinase (CASK) in controlling P2X3 receptor expression and function in trigeminal ganglia from Cacna1a R192Q-mutated knock-in (KI) mice, a genetic model for familial hemiplegic migraine type-1. KI ganglion neurons showed more abundant CASK/P2X3 receptor complex at membrane level, a result that likely originated from gain-of-function effects of R192Q-mutated CaV2.1 channels and downstream enhanced CaMKII activity. The selective CaV2.1 channel blocker ω-Agatoxin IVA and the CaMKII inhibitor KN-93 were sufficient to return CASK/P2X3 co-expression to WT levels. After CASK silencing, P2X3 receptor expression was decreased in both WT and KI ganglia, supporting the role of CASK in P2X3 receptor stabilization. This process was functionally observed as reduced P2X3 receptor currents. We propose that, in trigeminal sensory neurons, the CASK/P2X3 complex has a dynamic nature depending on intracellular calcium and related signaling, that are enhanced in a transgenic mouse model of genetic hemiplegic migraine.

Mutated CaV2.1 channels dysregulate CASK/P2X3 signaling in mouse trigeminal sensory neurons of R192Q Cacna1a knock-in mice

PubMed Central

2013-01-01

Background ATP-gated P2X3 receptors of sensory ganglion neurons are important transducers of pain as they adapt their expression and function in response to acute and chronic nociceptive signals. The present study investigated the role of calcium/calmodulin-dependent serine protein kinase (CASK) in controlling P2X3 receptor expression and function in trigeminal ganglia from Cacna1a R192Q-mutated knock-in (KI) mice, a genetic model for familial hemiplegic migraine type-1. Results KI ganglion neurons showed more abundant CASK/P2X3 receptor complex at membrane level, a result that likely originated from gain-of-function effects of R192Q-mutated CaV2.1 channels and downstream enhanced CaMKII activity. The selective CaV2.1 channel blocker ω-Agatoxin IVA and the CaMKII inhibitor KN-93 were sufficient to return CASK/P2X3 co-expression to WT levels. After CASK silencing, P2X3 receptor expression was decreased in both WT and KI ganglia, supporting the role of CASK in P2X3 receptor stabilization. This process was functionally observed as reduced P2X3 receptor currents. Conclusions We propose that, in trigeminal sensory neurons, the CASK/P2X3 complex has a dynamic nature depending on intracellular calcium and related signaling, that are enhanced in a transgenic mouse model of genetic hemiplegic migraine. PMID:24294842

Computational aero-acoustics for fan duct propagation and radiation. Current status and application to turbofan liner optimisation

NASA Astrophysics Data System (ADS)

Astley, R. J.; Sugimoto, R.; Mustafi, P.

2011-08-01

Novel techniques are presented to reduce noise from turbofan aircraft engines by optimising the acoustic treatment in engine ducts. The application of Computational Aero-Acoustics (CAA) to predict acoustic propagation and absorption in turbofan ducts is reviewed and a critical assessment of performance indicates that validated and accurate techniques are now available for realistic engine predictions. A procedure for integrating CAA methods with state of the art optimisation techniques is proposed in the remainder of the article. This is achieved by embedding advanced computational methods for noise prediction within automated and semi-automated optimisation schemes. Two different strategies are described and applied to realistic nacelle geometries and fan sources to demonstrate the feasibility of this approach for industry scale problems.

Cytoplasmic Location of α1A Voltage-Gated Calcium Channel C-Terminal Fragment (Cav2.1-CTF) Aggregate Is Sufficient to Cause Cell Death

PubMed Central

Takahashi, Makoto; Obayashi, Masato; Ishiguro, Taro; Sato, Nozomu; Niimi, Yusuke; Ozaki, Kokoro; Mogushi, Kaoru; Mahmut, Yasen; Tanaka, Hiroshi; Tsuruta, Fuminori; Dolmetsch, Ricardo; Yamada, Mitsunori; Takahashi, Hitoshi; Kato, Takeo; Mori, Osamu; Eishi, Yoshinobu; Mizusawa, Hidehiro; Ishikawa, Kinya

2013-01-01

The human α1A voltage-dependent calcium channel (Cav2.1) is a pore-forming essential subunit embedded in the plasma membrane. Its cytoplasmic carboxyl(C)-tail contains a small poly-glutamine (Q) tract, whose length is normally 4∼19 Q, but when expanded up to 20∼33Q, the tract causes an autosomal-dominant neurodegenerative disorder, spinocerebellar ataxia type 6 (SCA6). A recent study has shown that a 75-kDa C-terminal fragment (CTF) containing the polyQ tract remains soluble in normal brains, but becomes insoluble mainly in the cytoplasm with additional localization to the nuclei of human SCA6 Purkinje cells. However, the mechanism by which the CTF aggregation leads to neurodegeneration is completely elusive, particularly whether the CTF exerts more toxicity in the nucleus or in the cytoplasm. We tagged recombinant (r)CTF with either nuclear-localization or nuclear-export signal, created doxycyclin-inducible rat pheochromocytoma (PC12) cell lines, and found that the CTF is more toxic in the cytoplasm than in the nucleus, the observations being more obvious with Q28 (disease range) than with Q13 (normal-length). Surprisingly, the CTF aggregates co-localized both with cAMP response element-binding protein (CREB) and phosphorylated-CREB (p-CREB) in the cytoplasm, and Western blot analysis showed that the quantity of CREB and p-CREB were both decreased in the nucleus when the rCTF formed aggregates in the cytoplasm. In human brains, polyQ aggregates also co-localized with CREB in the cytoplasm of SCA6 Purkinje cells, but not in other conditions. Collectively, the cytoplasmic Cav2.1-CTF aggregates are sufficient to cause cell death, and one of the pathogenic mechanisms may be abnormal CREB trafficking in the cytoplasm and reduced CREB and p-CREB levels in the nuclei. PMID:23505410

Near-field sound radiation of fan tones from an installed turbofan aero-engine.

PubMed

McAlpine, Alan; Gaffney, James; Kingan, Michael J

2015-09-01