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Sample records for level npc inverter

  1. Modelling and control of a seven level NPC voltage source inverter. Application to high power induction machine drive

    NASA Astrophysics Data System (ADS)

    Gheraia, H.; Berkouk, E. M.; Manesse, G.

    2001-08-01

    In this paper, we study a new kind of continuous-alternating converters: a seven-level neutral point clamping (NPC) voltage source inverter (VSI). We propose this inverter for applications in high voltage and high power fields. In the first part, we develop the knowledge and the control models of this inverter using the connections functions of the semi-conductors. After that, we present two pulse width modulation (PWM) algorithms to control this converter using its control model. We propose these algorithms for digital implementation. This multilevel inverter is associated to the induction machine. The performances obtained are full of promise to use it in the high voltage and high power fields of electrical traction.

  2. Analysis and carrier-based modulation of Z-source NPC inverters

    NASA Astrophysics Data System (ADS)

    Dehghan, Seyed Mohammad; Mohamadian, Mustafa; Gharekhani, Reza

    2012-08-01

    Multi-level neutral-point-clamped (NPC) inverters are widely used in high and medium voltage applications. However, these inverters are only buck-type converters. Recently z-source NPC inverters have been proposed as the buck-boost three-level inverter. New inverters use a z-source network as the input stage. This article analyses the features and limitations of two main topologies of z-source NPC inverters (dual z-source network NPC inverter and single z-source network NPC inverter). The low-frequency ripple of the inductor current and the capacitor voltage of the z-source networks in the z-source NPC inverters are surveyed. This article also proposes two novel PWM methods for the z-source NPC inverters, which can be easily implemented experimentally. In the proposed methods, generated switching signals for the conventional NPC inverter are modified for the z-source NPC inverter using a simple logic circuit considering the boost factors and the power sharing ratio. The performance of the proposed simple PWM methods is verified by simulation and experimental results.

  3. Fault-tolerant three-level inverter

    DOEpatents

    Edwards, John; Xu, Longya; Bhargava, Brij B.

    2006-12-05

    A method for driving a neutral point clamped three-level inverter is provided. In one exemplary embodiment, DC current is received at a neutral point-clamped three-level inverter. The inverter has a plurality of nodes including first, second and third output nodes. The inverter also has a plurality of switches. Faults are checked for in the inverter and predetermined switches are automatically activated responsive to a detected fault such that three-phase electrical power is provided at the output nodes.

  4. Genetic demonstration of intestinal NPC1L1 as a major determinant of hepatic cholesterol and blood atherogenic lipoprotein levels

    PubMed Central

    Xie, Ping; Zhu, Hongling; Jia, Lin; Ma, Yinyan; Tang, Weiqing; Wang, Youlin; Xue, Bingzhong; Shi, Hang; Yu, Liqing

    2014-01-01

    Objective The correlation between intestinal cholesterol absorption values and plasma low-density lipoprotein-cholesterol (LDL-C) levels remains controversial. Niemann-Pick-C1-Like 1 (NPC1L1) is essential for intestinal cholesterol absorption, and is the target of ezetimibe, a cholesterol absorption inhibitor. However, studies with NPC1L1 knockout mice or ezetimibe cannot definitively clarify this correlation because NPC1L1 expression is not restricted to intestine in humans and mice. In this study we sought to genetically address this issue. Methods and results We developed a mouse model that lacks endogenous (NPC1L1) and LDL receptor (LDLR) (DKO), but transgenically expresses human NPC1L1 in gastrointestinal tract only (DKO/L1IntOnly mice). Our novel model eliminated potential effects of non-intestinal NPC1L1 on cholesterol homeostasis. We found that human NPC1L1 was localized at the intestinal brush border membrane of DKO/L1IntOnly mice. Cholesterol feeding induced formation of NPC1L1-positive vesicles beneath this membrane in an ezetimibe-sensitive manner. Compared to DKO mice, DKO/L1IntOnly mice showed significant increases in cholesterol absorption and blood/hepatic/biliary cholesterol. Increased blood cholesterol was restricted to very low-density lipoprotein (VLDL) and LDL fractions, which was associated with increased secretion and plasma levels of apolipoproteins B100 and B48. Additionally, DKO/L1IntOnly mice displayed decreased fecal cholesterol excretion and hepatic/intestinal expression of cholesterologenic genes. Ezetimibe treatment virtually reversed all of the transgene-related phenotypes in DKO/L1IntOnly mice. Conclusion Our findings from DKO/L1IntOnly mice clearly demonstrate that NPC1L1-mediated cholesterol absorption is a major determinant of blood levels of apolipoprotein B-containing atherogenic lipoproteins, at least in mice. PMID:25463095

  5. Reduced VLDL clearance in Apoe(-/-)Npc1(-/-) mice is associated with increased Pcsk9 and Idol expression and decreased hepatic LDL-receptor levels.

    PubMed

    Ishibashi, Minako; Masson, David; Westerterp, Marit; Wang, Nan; Sayers, Scott; Li, Rong; Welch, Carrie L; Tall, Alan R

    2010-09-01

    Niemann-Pick type C1 (NPC1) promotes the transport of LDL receptor (LDL-R)-derived cholesterol from late endosomes/lysosomes to other cellular compartments. NPC1-deficient cells showed impaired regulation of liver_X receptor (LXR) and sterol regulatory element-binding protein (SREBP) target genes. We observed that Apoe(-/-)Npc1(-/-) mice displayed a marked increase in total plasma cholesterol mainly due to increased VLDL, reflecting decreased clearance. Although nuclear SREBP-2 and Ldlr mRNA levels were increased in Apoe(-/-)Npc1(-/-) liver, LDL-R protein levels were decreased in association with marked induction of proprotein convertase subtilisin/kexin type 9 (Pcsk9) and inducible degrader of the LDL-R (Idol), both known to promote proteolytic degradation of LDL-R. While Pcsk9 is known to be an SREBP-2 target, marked upregulation of IDOL in Apoe(-/-)Npc1(-/-) liver was unexpected. However, several other LXR target genes also increased in Apoe(-/-)Npc1(-/-) liver, suggesting increased synthesis of endogenous LXR ligands secondary to activation of sterol biosynthesis. In conclusion, we demonstrate that NPC1 deficiency has a major impact on VLDL metabolism in Apoe(-/-) mice through modulation of hepatic LDL-R protein levels. In contrast to modest induction of hepatic IDOL with synthetic LXR ligands, a striking upregulation of IDOL in Apoe(-/-)Npc1(-/-) mice could indicate a role of endogenous LXR ligands in regulation of hepatic IDOL. PMID:20562239

  6. Identification of lysosomal Npc1-binding proteins: Cathepsin D activity is regulated by NPC1.

    PubMed

    Macías-Vidal, Judit; Guerrero-Hernández, Martina; Estanyol, Josep Maria; Aguado, Carmen; Knecht, Erwin; Coll, Maria Josep; Bachs, Oriol

    2016-01-01

    Niemann-Pick type C (NPC) disease is an inherited lysosomal storage disorder, characterized by severe neurodegeneration. It is mostly produced by mutations in the NPC1 gene, encoding for a protein of the late endosomes/lysosomes membrane, involved in cholesterol metabolism. However, the specific role of this protein in NPC disease still remains unknown. We aimed to identify Npc1-binding proteins in order to define new putative NPC1 lysosomal functions. By affinity chromatography using an Npc1 peptide (amino acids 1032-1066 of loop I), as bait, we fished 31 lysosomal proteins subsequently identified by LC-MS/MS. Most of them were involved in proteolysis and lipid catabolism and included the protease cathepsin D. Cathepsin D and NPC1 interaction was validated by immunoprecipitation and the functional relevance of this interaction was studied. We found that fibroblasts from NPC patients with low levels of NPC1 protein have high amounts of procathepsin D but reduced quantities of the mature protein, thus showing a diminished cathepsin D activity. The increase of NPC1 protein levels in NPC cells by treatment with the proteasome inhibitor bortezomib, induced an elevation of cathepsin D activity. All these results suggest a new lysosomal function of NPC1 as a regulator of cathepsin D processing and activity. PMID:26507101

  7. Prediction of 2-level PWM inverter efficiency using MATLAB/Simulink

    NASA Astrophysics Data System (ADS)

    Kim, Yoon-Ho; Kim, Seong-Je

    2015-10-01

    This article proposes a direct approach for the prediction of inverter efficiency using MATLAB/Simulink, instead of an indirect loss calculation approach based on analytical models. In analytical approach, efficiency is obtained by calculating individual losses separately, such as switching losses, conduction losses and harmonic losses using analytical models. However, this approach requires accurate analytical models and complicated calculations, due to the variation in the switching frequency, switching transient and modulation techniques. In the proposed approach, the actual waveform of the inverter system is directly generated using MATLAB/Simulink. The instantaneous voltage and current waveform including switching transients are generated. Thus, the proposed approach is very simple and convenient for efficiency prediction. The proposed approach also works for any system parameters or control methods, such as various pulse-width modulation (PWM) techniques, different switching frequencies, switching devices and load types. The proposed approach can be adopted for the efficiency prediction of any switching strategies and any types of inverters such as neutral-point-clamped (NPC) inverters, H bridge inverters and H5 topology, since the topologies are modelled as circuits in the MATLAB/Simulink program and no analytical model is required for the proposed approach. Furthermore, the proposed approach can provide operation techniques and conditions such as PWM techniques and switching frequency that offer high efficiency. In this article, inverter performance is evaluated for various PWM techniques and switching frequencies. The PWM technique and switching frequency that offer high efficiency is obtained. Finally, the proposed approach is verified by experimental results.

  8. Advanced Inverter Functions to Support High Levels of Distributed Solar: Policy and Regulatory Considerations (Brochure)

    SciTech Connect

    Not Available

    2014-11-01

    This paper explains how advanced inverter functions (sometimes called 'smart inverters') contribute to the integration of high levels of solar PV generation onto the electrical grid and covers the contributions of advanced functions to maintaining grid stability. Policy and regulatory considerations associated with the deployment of advanced inverter functions are also introduced.

  9. Pulmonary Abnormalities in Animal Models Due to Niemann-Pick Type C1 (NPC1) or C2 (NPC2) Disease

    PubMed Central

    Roszell, Blair R.; Tao, Jian-Qin; Yu, Kevin J.; Gao, Ling; Huang, Shaohui; Ning, Yue; Feinstein, Sheldon I.; Vite, Charles H.; Bates, Sandra R.

    2013-01-01

    Niemann-Pick C (NPC) disease is due to loss of NPC1 or NPC2 protein function that is required for unesterified cholesterol transport from the endosomal/lysosomal compartment. Though lung involvement is a recognized characteristic of Niemann-Pick type C disease, the pathological features are not well understood. We investigated components of the surfactant system in both NPC1 mutant mice and felines and in NPC2 mutant mice near the end of their expected life span. Histological analysis of the NPC mutant mice demonstrated thickened septae and foamy macrophages/leukocytes. At the level of electron microscopy, NPC1-mutant type II cells had uncharacteristically larger lamellar bodies (LB, mean area 2-fold larger), while NPC2-mutant cells had predominantly smaller lamellar bodies (mean area 50% of normal) than wild type. Bronchoalveolar lavage from NPC1 and NPC2 mutant mice had an approx. 4-fold and 2.5-fold enrichment in phospholipid, respectively, and an approx. 9-fold and 35-fold enrichment in cholesterol, consistent with alveolar lipidosis. Phospholipid and cholesterol also were elevated in type II cell LBs and lung tissue while phospholipid degradation was reduced. Enrichment of surfactant protein-A in the lung and surfactant of the mutant mice was found. Immunocytochemical results showed that cholesterol accumulated in the LBs of the type II cells isolated from the affected mice. Alveolar macrophages from the NPC1 and NPC2 mutant mice were enlarged compared to those from wild type mice and were enriched in phospholipid and cholesterol. Pulmonary features of NPC1 mutant felines reflected the disease described in NPC1 mutant mice. Thus, with the exception of lamellar body size, the lung phenotype seen in the NPC1 and NPC2 mutant mice were similar. The lack of NPC1 and NPC2 proteins resulted in a disruption of the type II cell surfactant system contributing to pulmonary abnormalities. PMID:23843985

  10. Photodynamic effect of curcumin on NPC/CNE2 cells.

    PubMed

    Koon, H; Leung, Albert W N; Yue, Kevin K M; Mak, Naiki K

    2006-01-01

    Nasopharyngeal carcinoma (NPC) is highly prevalent in Southern China. Radiotherapy is the primary treatment of NPC, but the rate of tumor recurrence is significant. Photodynamic therapy (PDT) and the use of natural compounds become one of the new approaches in the investigation of NPC treatment. PDT is an alternate method of cancer treatment while curcumin (CUR) is a compound derived from the traditional Chinese medicinal (TCM) herbs. The purpose of the study focuses on the photodynamic effect of CUR on one of the NPC cell lines, NPC/CNE2. Cytotoxicity and photocytotoxicity of CUR were evaluated by 3-(4,5-dimthyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Uptake kinetics of CUR in NPC/CNE2 was examined by flow cytometry. The mode of cell death induced by CUR was studied by fluorescence microscopy. Summarizing the results, CUR showed dark cytotoxicity as well as photocytotoxic effects on NPC/CNE2 cells. LC50 of CUR in the dark was about 16 microM. The cytotoxicity of CUR was enhanced by the irradiation of visible light and blue filtered light (maximum transmittance at 300 approximately 400 nm) with light doses of 300 kJ/m2 and 60 kJ/m2 respectively. NPC/CNE2 was found to rapidly take up CUR in the first hour of incubation, and the uptake kinetics steadily increased to a plateau level after 20 hr of incubation. Cell shrinkage and membrane bledding appeared under the observation of fluorescence microscopy. Such evidences proved that CUR might induce apoptosis on NPC/CNE2 cells. The preliminary study confirmed that CUR demonstrated dark cytotoxicity and photocytotoxicty to NPC/CNE2. The mode of action is likely to be induced by apoptotic pathway. CUR may be developed as a potential photosensitizer as well as a chemotherapeutic agent in clinical application. PMID:16566718

  11. The metamorphosis in the emission angular profile from an inverted two-level atoms system

    NASA Astrophysics Data System (ADS)

    Friedberg, Richard; Manassah, Jamal T.

    2009-08-01

    A rich variety of angular distributions in the cooperative emission from a sphere of inverted N two-level atoms are shown to result from the eigenstructure of the complex kernel of scalar photon theory exp( ik0R)/( ik0R). This angular distribution is sensitive both to the size of the sphere and to the instant of observation of the emission.

  12. Fundamental Frequency Switching Control of Seven-Level Hybrid Cascaded H-bridge Multilevel Inverter

    SciTech Connect

    Du, Zhong; Chiasson, John N; Ozpineci, Burak; Tolbert, Leon M

    2009-01-01

    This paper presents a cascaded H-bridge multilevel inverter that can be implemented using only a single dc power source and capacitors. Standard cascaded multilevel inverters require n dc sources for 2n + 1 levels. Without requiring transformers, the scheme proposed here allows the use of a single dc power source (e.g., a battery or a fuel cell stack) with the remaining n-1 dc sources being capacitors, which is referred to as hybrid cascaded H-bridge multilevel inverter (HCMLI) in this paper. It is shown that the inverter can simultaneously maintain the dc voltage level of the capacitors and choose a fundamental frequency switching pattern to produce a nearly sinusoidal output. HCMLI using only a single dc source for each phase is promising for high-power motor drive applications as it significantly decreases the number of required dc power supplies, provides high-quality output power due to its high number of output levels, and results in high conversion efficiency and low thermal stress as it uses a fundamental frequency switching scheme. This paper mainly discusses control of seven-level HCMLI with fundamental frequency switching control and how its modulation index range can be extended using triplen harmonic compensation.

  13. High performance control of a three-level IGBT inverter fed AC drive

    SciTech Connect

    Zhang, J.

    1995-12-31

    Three-level PWM inverters have been increasingly employed in industry and traction applications where high power and efficiency energy conversions are required. This paper presents a high performance control of a cage induction motor drive fed by a 100 Hp three-level IGBT inverter operating at a low switching frequency. A practical math model of the drive control system is established to aid in the control design to improve the system stability, dynamic performance and robustness over a wide speed range. The modeling and the simulation in Matlab/Simulink facilitate the self-tuning of the regulators in the multi-loop systems. The field oriented control and three-level space-vector modulation together with the drive protection and diagnostics are implemented in software based on a DSP TMS320C31. Experimental results based on the IGBT inverter prototype are given to verify the design and performance. Test results in motor common-mode voltage reduction and inverter neutral-point potential control re also briefly presented.

  14. A new balancing three level three dimensional space vector modulation strategy for three level neutral point clamped four leg inverter based shunt active power filter controlling by nonlinear back stepping controllers.

    PubMed

    Chebabhi, Ali; Fellah, Mohammed Karim; Kessal, Abdelhalim; Benkhoris, Mohamed F

    2016-07-01

    In this paper is proposed a new balancing three-level three dimensional space vector modulation (B3L-3DSVM) strategy which uses a redundant voltage vectors to realize precise control and high-performance for a three phase three-level four-leg neutral point clamped (NPC) inverter based Shunt Active Power Filter (SAPF) for eliminate the source currents harmonics, reduce the magnitude of neutral wire current (eliminate the zero-sequence current produced by single-phase nonlinear loads), and to compensate the reactive power in the three-phase four-wire electrical networks. This strategy is proposed in order to gate switching pulses generation, dc bus voltage capacitors balancing (conserve equal voltage of the two dc bus capacitors), and to switching frequency reduced and fixed of inverter switches in same times. A Nonlinear Back Stepping Controllers (NBSC) are used for regulated the dc bus voltage capacitors and the SAPF injected currents to robustness, stabilizing the system and to improve the response and to eliminate the overshoot and undershoot of traditional PI (Proportional-Integral). Conventional three-level three dimensional space vector modulation (C3L-3DSVM) and B3L-3DSVM are calculated and compared in terms of error between the two dc bus voltage capacitors, SAPF output voltages and THDv, THDi of source currents, magnitude of source neutral wire current, and the reactive power compensation under unbalanced single phase nonlinear loads. The success, robustness, and the effectiveness of the proposed control strategies are demonstrated through simulation using Sim Power Systems and S-Function of MATLAB/SIMULINK. PMID:27018144

  15. A Five-Level Cascade Multilevel Inverter Three-Phase Motor Drive Using a Single DC Source

    SciTech Connect

    Chiasson, J. N.

    2006-10-01

    A method is presented showing that a 5-level cascade multilevel inverter for a three-phase permanent magnet sychronous motor drive can be implemented using only a single DC link to supply a standard 3-leg inverter along with three full H-bridges supplied by capacitors. It is shown that the capacitor voltages can be regulated while achieving an output voltage waveform that is 20% greater than that obained using the standard 3-leg inverter alone. Finally conditions are given in terms of the power factor and modulation index that determine when the capacitor voltage can regulated.

  16. Advanced Inverter Technology for High Penetration Levels of PV Generation in Distribution Systems

    SciTech Connect

    Schauder, C.

    2014-03-01

    This subcontract report was completed under the auspices of the NREL/SCE High-Penetration Photovoltaic (PV) Integration Project, which is co-funded by the U.S. Department of Energy (DOE) Office of Energy Efficiency and Renewable Energy (EERE) and the California Solar Initiative (CSI) Research, Development, Demonstration, and Deployment (RD&D) program funded by the California Public Utility Commission (CPUC) and managed by Itron. This project is focused on modeling, quantifying, and mitigating the impacts of large utility-scale PV systems (generally 1-5 MW in size) that are interconnected to the distribution system. This report discusses the concerns utilities have when interconnecting large PV systems that interconnect using PV inverters (a specific application of frequency converters). Additionally, a number of capabilities of PV inverters are described that could be implemented to mitigate the distribution system-level impacts of high-penetration PV integration. Finally, the main issues that need to be addressed to ease the interconnection of large PV systems to the distribution system are presented.

  17. A Five-Level Three-Phase Cascade Multilevel Inverter Using a Single DC Source for a PM Synchronous Motor Drive

    SciTech Connect

    Ozpineci, Burak; Chiasson, John N; Tolbert, Leon M

    2007-01-01

    The interest here is in using a single DC power source to construct a 3-phase 5-level cascade multilevel inverter to be used as a drive for a PM traction motor. The 5-level inverter consists of a standard 3-leg inverter (one leg for each phase) and an H-bridge in series with each inverter leg, which use a capacitor as a DC source. It is shown that one can simultaneously maintain the regulation of the capacitor voltage while achieving an output voltage waveform which is 25% higher than that obtained using a standard 3-leg inverter by itself.

  18. Inverted barometer contributions to recent sea level changes along the northeast coast of North America

    NASA Astrophysics Data System (ADS)

    Piecuch, Christopher G.; Ponte, Rui M.

    2015-07-01

    Regional sea level (SL) changes reflect dynamic and isostatic ocean effects. Recent works have interpreted accelerated and extreme SL changes along the northeast coast of North America primarily in terms of dynamic changes; however, dedicated study of isostatic changes related to surface atmospheric pressure loading—the inverted barometer (IB) effect—has been lacking. This investigation uses five different atmospheric pressure products to analyze the influence of the IB effect on annual mean SL from tide gauge records. The IB effect explains ˜25% of interannual SL variance and accounts for ˜50% of the magnitude of a recent extreme event of SL rise along Atlantic Canada and New England. Estimated IB effects also amount to ˜10-30% of recent multidecadal SL accelerations over the Mid-Atlantic Bight and Southern New England. These findings reiterate the need for careful estimation and removal of isostatic effects for studies of dynamic SL.

  19. A single-phase multi-level D-STATCOM inverter using modular multi-level converter (MMC) topology for renewable energy sources

    NASA Astrophysics Data System (ADS)

    Sotoodeh, Pedram

    This dissertation presents the design of a novel multi-level inverter with FACTS capability for small to mid-size (10-20kW) permanent-magnet wind installations using modular multi-level converter (MMC) topology. The aim of the work is to design a new type of inverter with D-STATCOM option to provide utilities with more control on active and reactive power transfer of distribution lines. The inverter is placed between the renewable energy source, specifically a wind turbine, and the distribution grid in order to fix the power factor of the grid at a target value, regardless of wind speed, by regulating active and reactive power required by the grid. The inverter is capable of controlling active and reactive power by controlling the phase angle and modulation index, respectively. The unique contribution of the proposed work is to combine the two concepts of inverter and D-STATCOM using a novel voltage source converter (VSC) multi-level topology in a single unit without additional cost. Simulations of the proposed inverter, with 5 and 11 levels, have been conducted in MATLAB/Simulink for two systems including 20 kW/kVAR and 250 W/VAR. To validate the simulation results, a scaled version (250 kW/kVAR) of the proposed inverter with 5 and 11 levels has been built and tested in the laboratory. Experimental results show that the reduced-scale 5- and 11-level inverter is able to fix PF of the grid as well as being compatible with IEEE standards. Furthermore, total cost of the prototype models, which is one of the major objectives of this research, is comparable with market prices.

  20. A Single Residue in Ebola Virus Receptor NPC1 Influences Cellular Host Range in Reptiles.

    PubMed

    Ndungo, Esther; Herbert, Andrew S; Raaben, Matthijs; Obernosterer, Gregor; Biswas, Rohan; Miller, Emily Happy; Wirchnianski, Ariel S; Carette, Jan E; Brummelkamp, Thijn R; Whelan, Sean P; Dye, John M; Chandran, Kartik

    2016-01-01

    Filoviruses are the causative agents of an increasing number of disease outbreaks in human populations, including the current unprecedented Ebola virus disease (EVD) outbreak in western Africa. One obstacle to controlling these epidemics is our poor understanding of the host range of filoviruses and their natural reservoirs. Here, we investigated the role of the intracellular filovirus receptor, Niemann-Pick C1 (NPC1) as a molecular determinant of Ebola virus (EBOV) host range at the cellular level. Whereas human cells can be infected by EBOV, a cell line derived from a Russell's viper (Daboia russellii) (VH-2) is resistant to infection in an NPC1-dependent manner. We found that VH-2 cells are resistant to EBOV infection because the Russell's viper NPC1 ortholog bound poorly to the EBOV spike glycoprotein (GP). Analysis of panels of viper-human NPC1 chimeras and point mutants allowed us to identify a single amino acid residue in NPC1, at position 503, that bidirectionally influenced both its binding to EBOV GP and its viral receptor activity in cells. Significantly, this single residue change perturbed neither NPC1's endosomal localization nor its housekeeping role in cellular cholesterol trafficking. Together with other recent work, these findings identify sequences in NPC1 that are important for viral receptor activity by virtue of their direct interaction with EBOV GP and suggest that they may influence filovirus host range in nature. Broader surveys of NPC1 orthologs from vertebrates may delineate additional sequence polymorphisms in this gene that control susceptibility to filovirus infection. IMPORTANCE Identifying cellular factors that determine susceptibility to infection can help us understand how Ebola virus is transmitted. We asked if the EBOV receptor Niemann-Pick C1 (NPC1) could explain why reptiles are resistant to EBOV infection. We demonstrate that cells derived from the Russell's viper are not susceptible to infection because EBOV cannot bind to

  1. A Single Residue in Ebola Virus Receptor NPC1 Influences Cellular Host Range in Reptiles

    PubMed Central

    Ndungo, Esther; Herbert, Andrew S.; Raaben, Matthijs; Obernosterer, Gregor; Biswas, Rohan; Miller, Emily Happy; Wirchnianski, Ariel S.; Carette, Jan E.; Brummelkamp, Thijn R.; Whelan, Sean P.

    2016-01-01

    ABSTRACT Filoviruses are the causative agents of an increasing number of disease outbreaks in human populations, including the current unprecedented Ebola virus disease (EVD) outbreak in western Africa. One obstacle to controlling these epidemics is our poor understanding of the host range of filoviruses and their natural reservoirs. Here, we investigated the role of the intracellular filovirus receptor, Niemann-Pick C1 (NPC1) as a molecular determinant of Ebola virus (EBOV) host range at the cellular level. Whereas human cells can be infected by EBOV, a cell line derived from a Russell’s viper (Daboia russellii) (VH-2) is resistant to infection in an NPC1-dependent manner. We found that VH-2 cells are resistant to EBOV infection because the Russell’s viper NPC1 ortholog bound poorly to the EBOV spike glycoprotein (GP). Analysis of panels of viper-human NPC1 chimeras and point mutants allowed us to identify a single amino acid residue in NPC1, at position 503, that bidirectionally influenced both its binding to EBOV GP and its viral receptor activity in cells. Significantly, this single residue change perturbed neither NPC1’s endosomal localization nor its housekeeping role in cellular cholesterol trafficking. Together with other recent work, these findings identify sequences in NPC1 that are important for viral receptor activity by virtue of their direct interaction with EBOV GP and suggest that they may influence filovirus host range in nature. Broader surveys of NPC1 orthologs from vertebrates may delineate additional sequence polymorphisms in this gene that control susceptibility to filovirus infection. IMPORTANCE Identifying cellular factors that determine susceptibility to infection can help us understand how Ebola virus is transmitted. We asked if the EBOV receptor Niemann-Pick C1 (NPC1) could explain why reptiles are resistant to EBOV infection. We demonstrate that cells derived from the Russell’s viper are not susceptible to infection because EBOV

  2. Clues to the mechanism of cholesterol transfer from the structure of NPC1 middle lumenal domain bound to NPC2.

    PubMed

    Li, Xiaochun; Saha, Piyali; Li, Jian; Blobel, Günter; Pfeffer, Suzanne R

    2016-09-01

    Export of LDL-derived cholesterol from lysosomes requires the cooperation of the integral membrane protein Niemann-Pick C1 (NPC1) and a soluble protein, Niemann-Pick C2 (NPC2). Mutations in the genes encoding these proteins lead to Niemann-Pick disease type C (NPC). NPC2 binds to NPC1's second (middle), lumenally oriented domain (MLD) and transfers cholesterol to NPC1's N-terminal domain (NTD). Here, we report the 2.4-Å resolution crystal structure of a complex of human NPC1-MLD and NPC2 bearing bound cholesterol-3-O-sulfate. NPC1-MLD uses two protruding loops to bind NPC2, analogous to its interaction with the primed Ebola virus glycoprotein. Docking of the NPC1-NPC2 complex onto the full-length NPC1 structure reveals a direct cholesterol transfer tunnel between NPC2 and NTD cholesterol binding pockets, supporting the "hydrophobic hand-off" cholesterol transfer model. PMID:27551080

  3. Cholesterol Accumulation Is Associated with Lysosomal Dysfunction and Autophagic Stress in Npc1−/− Mouse Brain

    PubMed Central

    Liao, Guanghong; Yao, Yueqin; Liu, Jihua; Yu, Zhang; Cheung, Simon; Xie, Ang; Liang, Xiaoli; Bi, Xiaoning

    2007-01-01

    Niemann-Pick type C (NPC) disease is an autosomal recessive disorder caused by mutations of NPC1 and NPC2 genes. Progressive neurodegeneration that accompanies NPC is fatal, but the underlying mechanisms are still poorly understood. In the present study, we characterized the association of autophagic-lysosomal dysfunction with cholesterol accumulation in Npc1−/− mice during postnatal development. Brain levels of lysosomal cathepsin D were significantly higher in mutant than in wild-type mice. Increases in cathepsin D occurred first in neurons and later in astrocytes and microglia and were both spatially and temporally associated with intracellular cholesterol accumulation and neurodegeneration. Furthermore, levels of ubiquitinated proteins were higher in endosomal/lysosomal fractions of brains from Npc1−/− mice than from wild-type mice. Immunoblotting results showed that levels of LC3-II were significantly higher in brains of mutant than wild-type mice. Combined LC3 immunofluorescence and filipin staining showed that LC3 accumulated within filipin-labeled cholesterol clusters inside Purkinje cells. Electron microscopic examination revealed the existence of autophagic vacuole-like structures and multivesicles in brains from Npc1−/− mice. These results provide strong evidence that cholesterol accumulation-induced changes in autophagy-lysosome function are closely associated with neurodegeneration in NPC. PMID:17631520

  4. The clathrin adaptor Numb regulates intestinal cholesterol absorption through dynamic interaction with NPC1L1.

    PubMed

    Li, Pei-Shan; Fu, Zhen-Yan; Zhang, Ying-Yu; Zhang, Jin-Hui; Xu, Chen-Qi; Ma, Yi-Tong; Li, Bo-Liang; Song, Bao-Liang

    2014-01-01

    Hypercholesterolemia, typically due to excessive cholesterol uptake, is a major risk factor for cardiovascular disease, which is responsible for ∼50% of all deaths in developed societies. Although it has been shown that intestinal cholesterol absorption is mediated by vesicular endocytosis of the Niemann-Pick C1-like 1 (NPC1L1) protein, the mechanism of sterol-stimulated NPC1L1 internalization is still mysterious. Here, we identified an endocytic peptide signal, YVNXXF (where X stands for any amino acid), in the cytoplasmic C-terminal tail of NPC1L1. Cholesterol binding on the N-terminal domain of NPC1L1 released the YVNXXF-containing region of NPC1L1 from association with the plasma membrane and enabled Numb binding. We also found that Numb, a clathrin adaptor, specifically recognized this motif and recruited clathrin for internalization. Disrupting the NPC1L1-Numb interaction decreased cholesterol uptake. Ablation of Numb in mouse intestine significantly reduced dietary cholesterol absorption and plasma cholesterol level. Together, these data show that Numb is a pivotal protein for intestinal cholesterol absorption and may provide a therapeutic target for hypercholesterolemia. PMID:24336247

  5. Inverting Glacial Isostatic Adjustment with Paleo Sea Level Records using Bayesian Framework and Burgers Rheology

    NASA Astrophysics Data System (ADS)

    Caron, L.; Metivier, L.; Greff-Lefftz, M.; Fleitout, L.; Rouby, H.

    2015-12-01

    Glacial Isostatic Adjustment models most often assume a mantle with a viscoelastic Maxwell rheology and a given ice history model. Here we use a Bayesian Monte Carlo with Markov Chains formalism to invert the global GIA signal simultaneously for the mechanical properties of the mantle and for the volume of the various ice-sheets using as starting ice models two distinct previously published ice histories. Burgers as well as Maxwell rheologies are considered.The fitted data consist of 5720 paleo sea level records from the last 35kyrs, with a world-wide distribution. Our ambition is to present not only the best fitting model, but also the range of possible solutions (within the explored space of parameters) with their respective probability of explaining the data, and thus reveal the trade-off effects and range of uncertainty affecting the parameters. Our a posteriori probality maps exhibit in all cases two distinct peaks: both are characterized by an upper mantle viscosity around 5.1020Pa.s but one of the peaks features a lower mantle viscosity around 3.1021Pa.s while the other indicates lower mantle viscosity of more than 1.1022Pa.s. The global maximum depends upon the starting ice history and the chosen rheology: the first peak (P1) has the highest probability only in the case with a Maxwell rheology and ice history based on ICE-5G, while the second peak (P2) is favored when using ANU-based ice history or Burgers rheology, and is our preferred solution as it is also consistent with long-term geodynamics and gravity gradients anomalies over Laurentide. P2 is associated with larger volumes for the Laurentian and Fennoscandian ice-sheets and as a consequence of total ice volume balance, smaller volumes for the Antactic ice-sheet. This last point interfers with the estimate of present-day ice-melting in Antarctica from GRACE data. Finally, we find that P2 with Burgers rheology favors the existence of a tectosphere, i.e. a viscous sublithospheric layer.

  6. Improved PWM control for GTO inverters with pulse number modulation

    SciTech Connect

    Tadakuma, Susuma; Tanaka, Shigeru; Miura, Kazutoshi; Ofosu-Amaah, W.

    1996-05-01

    This paper proposes pulse number modulation (PNM)-assisted pulse-width modulation (PWM) control to improve the modulation factor of bridge inverters and to solve voltage uncontrollability in neutral point clamped (NPC) inverters. The basic idea is to enlarge the linear region of PWM control via PNM technology. The authors will show the following through simulation and experimental results: (1) conventional bridge inverters can utilize at most 80% of the nominal inverter capacity because of the limit of the modulation factor. The PWM and PNM combined control is able to improve the modulation factor up to approximately 1.0; (2) the PWM and PNM control enables linear voltage control in the NPC inverter even for an extremely small reference. The PNM technology also contributes to a reduction in switching losses.

  7. Phase-dependent high refractive index without absorption in a four-level inverted-Y atomic system

    SciTech Connect

    Zhi-Qiang Zeng; Fu-Ti Liu; Yu-Ping Wang; Zeng-Hui Gao

    2015-01-31

    We consider a closed four-level inverted-Y system in the presence and the absence of a microwave field. It is found that due to the quantum coherence between the two lower levels, either induced by the spontaneous decay or by the microwave field, the refraction – absorption properties of the system can be modulated by controlling the relative phase of the applied fields in both driven ways. In particular, by properly setting the values of the relative phase, the desirable high index of refraction without absorption can be achieved. (nonlinear optical phenomena)

  8. Neuronal Loss of Drosophila NPC1a Causes Cholesterol Aggregation and Age-Progressive Neurodegeneration

    PubMed Central

    Phillips, Scott E.; Woodruff, E. A.; Liang, Ping; Patten, Meaghan; Broadie, Kendal

    2009-01-01

    The mistrafficking and consequent cytoplasmic accumulation of cholesterol and sphingolipids is linked to multiple neurodegenerative diseases. One class of disease, the sphingolipid storage diseases, includes Niemann-Pick Disease Type C (NPC) caused predominantly (95%) by mutation of the NPC1 gene. A disease model has been established through mutation of Drosophila NPC1a (dnpc1a). Null mutants display early lethality due to loss of cholesterol-dependent ecdysone steroid hormone production. Null mutants rescued to adults by restoring ecdysone production mimic human NPC patients with progressive motor defects and reduced life spans. Analysis of dnpc1a null brains shows elevated overall cholesterol levels and progressive accumulation of filipin-positive cholesterol aggregates within brain and retina, as well as isolated cultured brain neurons. Ultrastructural imaging of dnpc1a mutant brains reveals age-progressive accumulation of striking multilamellar and multivesicular organelles, preceding the onset of neurodegeneration. Consistently, electroretinogram (ERG) recordings show age-progressive loss of phototransduction and photoreceptor synaptic transmission. Early lethality, movement impairments, neuronal cholesterol deposits, accumulation of multilamellar bodies and age-dependent neurodegeneration are all rescued by targeted neuronal expression of a wildtype dnpc1a transgene. Interestingly, targeted expression of dnpc1a in glia also provides limited rescue of adult lethality. Generation of dnpc1a null mutant neuron clones in the brain reveals cell autonomous requirements for dNPC1a in cholesterol and membrane trafficking. These data demonstrate a requirement for dNPC1a in the maintenance of neuronal function and viability, and show that loss of dNPC1a in neurons mimics the human neurodegenerative condition. PMID:18579730

  9. Neuronal loss of Drosophila NPC1a causes cholesterol aggregation and age-progressive neurodegeneration.

    PubMed

    Phillips, Scott E; Woodruff, E A; Liang, Ping; Patten, Meaghan; Broadie, Kendal

    2008-06-25

    The mistrafficking and consequent cytoplasmic accumulation of cholesterol and sphingolipids is linked to multiple neurodegenerative diseases. One class of disease, the sphingolipid storage diseases, includes Niemann-Pick disease type C (NPC), caused predominantly (95%) by mutation of the NPC1 gene. A disease model has been established through mutation of Drosophila NPC1a (dnpc1a). Null mutants display early lethality attributable to loss of cholesterol-dependent ecdysone steroid hormone production. Null mutants rescued to adults by restoring ecdysone production mimic human NPC patients with progressive motor defects and reduced life spans. Analysis of dnpc1a null brains shows elevated overall cholesterol levels and progressive accumulation of filipin-positive cholesterol aggregates within brain and retina, as well as isolated cultured brain neurons. Ultrastructural imaging of dnpc1a mutant brains reveals age-progressive accumulation of striking multilamellar and multivesicular organelles, preceding the onset of neurodegeneration. Consistently, electroretinogram recordings show age-progressive loss of phototransduction and photoreceptor synaptic transmission. Early lethality, movement impairments, neuronal cholesterol deposits, accumulation of multilamellar bodies, and age-dependent neurodegeneration are all rescued by targeted neuronal expression of a wild-type dnpc1a transgene. Interestingly, targeted expression of dnpc1a in glia also provides limited rescue of adult lethality. Generation of dnpc1a null mutant neuron clones in the brain reveals cell-autonomous requirements for dNPC1a in cholesterol and membrane trafficking. These data demonstrate a requirement for dNPC1a in the maintenance of neuronal function and viability and show that loss of dNPC1a in neurons mimics the human neurodegenerative condition. PMID:18579730

  10. Diagnostic tests for Niemann-Pick disease type C (NP-C): A critical review.

    PubMed

    Vanier, Marie T; Gissen, Paul; Bauer, Peter; Coll, Maria J; Burlina, Alberto; Hendriksz, Christian J; Latour, Philippe; Goizet, Cyril; Welford, Richard W D; Marquardt, Thorsten; Kolb, Stefan A

    2016-08-01

    Niemann-Pick disease type C (NP-C) is a neurovisceral lysosomal cholesterol trafficking and lipid storage disorder caused by mutations in one of the two genes, NPC1 or NPC2. Diagnosis has often been a difficult task, due to the wide range in age of onset of NP-C and clinical presentation of the disease, combined with the complexity of the cell biology (filipin) laboratory testing, even in combination with genetic testing. This has led to substantial delays in diagnosis, largely depending on the access to specialist centres and the level of knowledge about NP-C of the physician in the area. In recent years, advances in mass spectrometry has allowed identification of several sensitive plasma biomarkers elevated in NP-C (e.g. cholestane-3β,5α,6β-triol, lysosphingomyelin isoforms and bile acid metabolites), which, together with the concomitant progress in molecular genetic technology, have greatly impacted the strategy of laboratory testing. Specificity of the biomarkers is currently under investigation and other pathologies are being found to also result in elevations. Molecular genetic testing also has its limitations, notably with unidentified mutations and the classification of new variants. This review is intended to increase awareness on the currently available approaches to laboratory diagnosis of NP-C, to provide an up to date, comprehensive and critical evaluation of the various techniques (cell biology, biochemical biomarkers and molecular genetics), and to briefly discuss ongoing/future developments. The use of current tests in proper combination enables a rapid and correct diagnosis in a large majority of cases. However, even with recent progress, definitive diagnosis remains challenging in some patients, for whom combined genetic/biochemical/cytochemical markers do not provide a clear answer. Expertise and reference laboratories thus remain essential, and further work is still required to fulfill unmet needs. PMID:27339554

  11. Modes competition in superradiant emission from an inverted sub-wavelength thick slab of two-level atoms

    NASA Astrophysics Data System (ADS)

    Manassah, Jamal T.

    2016-08-01

    Using the expansion in the eigenmodes of 1-D Lienard-Wiechert kernel, the temporal and spectral profiles of the radiation emitted by a fully inverted collection of two-level atoms in a sub-wavelength slab geometry are computed. The initial number of amplifying modes determine the specific regime of radiation. In particular, the temporal profile of the field intensity is oscillatory and the spectral profile is non-Lorentzian with two unequal height peaks in a narrow band centered at the slab thickness value at which the real parts of the lowest order odd and even eigenvalues are equal.

  12. An advanced static var compensator based on a three level IGBT inverter modelling analysis and active power filtering

    NASA Astrophysics Data System (ADS)

    Draou, Azeddine

    2012-12-01

    This paper presents the dynamic performance analysis of an Advanced Static Var Compensator (ASVC) using three-level neutral point-clamped voltage source inverter. The paper presents the principles of operating and the method of reference currents generation. The dynamic behaviour of the system is further analysed using Matlab/Simulink with SimPower Systems toolbox through a set of simulation tests. The results obtained have been applied to an active power filter which might lead to the design of a robust controller for current harmonics and reactive power applications

  13. RNA Export through the NPC in Eukaryotes.

    PubMed

    Okamura, Masumi; Inose, Haruko; Masuda, Seiji

    2015-01-01

    In eukaryotic cells, RNAs are transcribed in the nucleus and exported to the cytoplasm through the nuclear pore complex. The RNA molecules that are exported from the nucleus into the cytoplasm include messenger RNAs (mRNAs), ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), small nuclear RNAs (snRNAs), micro RNAs (miRNAs), and viral mRNAs. Each RNA is transported by a specific nuclear export receptor. It is believed that most of the mRNAs are exported by Nxf1 (Mex67 in yeast), whereas rRNAs, snRNAs, and a certain subset of mRNAs are exported in a Crm1/Xpo1-dependent manner. tRNAs and miRNAs are exported by Xpot and Xpo5. However, multiple export receptors are involved in the export of some RNAs, such as 60S ribosomal subunit. In addition to these export receptors, some adapter proteins are required to export RNAs. The RNA export system of eukaryotic cells is also used by several types of RNA virus that depend on the machineries of the host cell in the nucleus for replication of their genome, therefore this review describes the RNA export system of two representative viruses. We also discuss the NPC anchoring-dependent mRNA export factors that directly recruit specific genes to the NPC. PMID:25802992

  14. RNA Export through the NPC in Eukaryotes

    PubMed Central

    Okamura, Masumi; Inose, Haruko; Masuda, Seiji

    2015-01-01

    In eukaryotic cells, RNAs are transcribed in the nucleus and exported to the cytoplasm through the nuclear pore complex. The RNA molecules that are exported from the nucleus into the cytoplasm include messenger RNAs (mRNAs), ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), small nuclear RNAs (snRNAs), micro RNAs (miRNAs), and viral mRNAs. Each RNA is transported by a specific nuclear export receptor. It is believed that most of the mRNAs are exported by Nxf1 (Mex67 in yeast), whereas rRNAs, snRNAs, and a certain subset of mRNAs are exported in a Crm1/Xpo1-dependent manner. tRNAs and miRNAs are exported by Xpot and Xpo5. However, multiple export receptors are involved in the export of some RNAs, such as 60S ribosomal subunit. In addition to these export receptors, some adapter proteins are required to export RNAs. The RNA export system of eukaryotic cells is also used by several types of RNA virus that depend on the machineries of the host cell in the nucleus for replication of their genome, therefore this review describes the RNA export system of two representative viruses. We also discuss the NPC anchoring-dependent mRNA export factors that directly recruit specific genes to the NPC. PMID:25802992

  15. Milliwatt dc/dc Inverter

    NASA Technical Reports Server (NTRS)

    Mclyman, C. W.

    1983-01-01

    Compact dc/dc inverter uses single integrated-circuit package containing six inverter gates that generate and amplify 100-kHz square-wave switching signal. Square-wave switching inverts 10-volt local power to isolated voltage at another desired level. Relatively high operating frequency reduces size of filter capacitors required, resulting in small package unit.

  16. Inverting the Linear Algebra Classroom

    ERIC Educational Resources Information Center

    Talbert, Robert

    2014-01-01

    The inverted classroom is a course design model in which students' initial contact with new information takes place outside of class meetings, and students spend class time on high-level sense-making activities. The inverted classroom model is so called because it inverts or "flips" the usual classroom design where typically class…

  17. Genetic variation at the NPC1L1 gene locus, plasma lipoproteins, and heart disease risk in the elderly

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Niemann-Pick C1-like 1 protein (NPC1L1) plays a critical role in intestinal cholesterol absorption. Our objective was to examine whether five variants (-133A>G, -18A>C, L272L, V1296V, and U3_28650A>G) at the NPC1L1 gene have effects on lipid levels, prevalence, and incidence of coronary heart diseas...

  18. Niemann-Pick C1-Like 1 (NPC1L1) Inhibition and Cardiovascular Diseases.

    PubMed

    Pirillo, A; Catapano, A L; Norata, G D

    2016-01-01

    Circulating levels of cholesterol are derived from either endogenous production or intestinal absorption of dietary and biliary cholesterol. Niemann-Pick C1-Like 1 (NPC1L1) is a transmembrane protein that plays a key role in the intestinal absorption of cholesterol by facilitating its uptake through vesicular endocytosis. NPC1L1 is the molecular target of ezetimibe which binds its extracellular loop and inhibits sterol absorption without affecting the absorption of other molecules. Ezetimibe significantly reduces plasma levels of total and low density lipoprotein cholesterol (LDL-C) as monotherapy or when added to statins, the association with a low dose of statin is of particular interest for patients experiencing statin-related side effects. The recent results of the IMPROVE-IT study, which evaluated the cardiovascular effect of ezetimibe added to simvastatin therapy in subjects who had had an acute coronary syndrome and with LDL-C levels within the recommended range, showed that a further LDL-C lowering reduced the incidence of cardiovascular events. To date, ezetimibe represents the only inhibitor of NPC1L1 available for clinical use, however, novel aminoß- lactam ezetimibe derivatives have been synthesized and their efficacy to inhibit NPC1L1 protein and decrease plasma cholesterol levels is under evaluation. PMID:26923679

  19. Pulmonary function and pathology in hydroxypropyl-beta-cyclodextin-treated and untreated Npc1⁻/⁻ mice.

    PubMed

    Muralidhar, Akshay; Borbon, Ivan A; Esharif, Dyadin M; Ke, Wangjing; Manacheril, Rinu; Daines, Michael; Erickson, Robert P

    2011-06-01

    Lung dysfunction is an important part of the pathology of the neurodegenerative disorder, Niemann-Pick C1 (NPC1). We have studied the pulmonary disease in the Npc1(NIH/NIH) mouse model. On histology, we find large numbers of alveolar foamy macrophages but no alveolar proteinosis. Lung weight as percent of body weight was markedly increased; using the flexiVent small animal ventilator (SCIREQ, Inc.), we find inspiratory capacity, elastance and hysterisivity to be increased while resistance was not changed. Cholesterol measurements show a doubling of lung cholesterol levels. Collagen is also increased. Treatment of Npc1(-/-) mice with hydroxypropyl-β-cyclodextrin (HPBCD), despite efficacious effects in brain and liver, results in little difference from age-matched controls (using a CNS-expressed transgene to extend the life expectancy of the Npc1(-/-) mice) for these variables. PMID:21459030

  20. The NPC: A Higher Priority for Networking Policy

    ERIC Educational Resources Information Center

    Kuhns, Jeff C.

    2006-01-01

    This article discusses the scope of activities of the Network Policy Council (NPC), which has been designed to provide a more direct channel of communications within EDUCAUSE and to provide policy formulation more visibility. The NPC is an advisory council to EDUCAUSE whose members are selected from those who have interest in this area and are…

  1. A DC-Voltage-Balancing Circuit for a Five-Level Diode-Clamped PWM Inverter Intended for Motor Drives

    NASA Astrophysics Data System (ADS)

    Hasegawa, Kazunori; Akagi, Hirofumi

    This paper proposes a new dc-voltage-balancing circuit for a five-level diode-clamped inverter intended for a medium-voltage motor drive. This circuit consists of two unidirectional choppers and a single coupled inductor with two galvanically-isolated windings. The dc magnetic fluxes in the magnetic core, which are generated by the two windings, cancel out each other. Therefore, the inductor does not generate any dc-magnetic flux in the magnetic core. This makes the inductor compact by a factor of six compared to previously used balancing circuits containing two non-coupled inductors. Experimental results obtained from a 200-V 5.5-kW downscaled model verify that the dc mean voltages of the four split dc capacitors are balanced well under all operating conditions.

  2. Cholesterol signaling at the endoplasmic reticulum occurs in npc1(-/-) but not in npc1(-/-), LDLR(-/-) mice.

    PubMed

    Erickson, R P; Kiela, M; Garver, W S; Krishnan, K; Heidenreich, R A

    2001-06-01

    It remains controversial whether deficiency of the Niemann-Pick C1 (npc1) protein results in altered cholesterol signaling at the endoplasmic reticulum (ER). In this report, we have measured the processed, nuclear form of sterol regulatory element binding protein (SREBP)-1 in livers of npc1 wild-type, heterozygous, and homozygous deficient mice, alone, and in combination with deficiencies of the low density lipoprotein receptor (LDLR) or the multiple drug resistant (mdr)1a, P-glycoprotein. Cleavage of SREBPs to activated forms normally occurs when the ER is deficient in cholesterol. A large decrease in processed SREBP-1 was evident in fasted npc1(-/-) mice and npc1(-/-), mdr1a(-/-) mice, with no decrease evident in npc1(-/-), LDLR(-/-) mice. These results suggest that the increase in cellular cholesterol which occurs in npc1(-/-) and in npc1(-/-), mdr1a(-/-) mice includes the sites responsible for cholesterol signaling, while the similar increase in cholesterol found in npc1(-/-), LDLR(-/-) mice does not. PMID:11394880

  3. Epigenetic modulation of intestinal cholesterol transporter Niemann-Pick C1-like 1 (NPC1L1) gene expression by DNA methylation.

    PubMed

    Malhotra, Pooja; Soni, Vinay; Kumar, Anoop; Anbazhagan, Arivarasu N; Dudeja, Amish; Saksena, Seema; Gill, Ravinder K; Dudeja, Pradeep K; Alrefai, Waddah A

    2014-08-15

    Intestinal NPC1L1 transporter is essential for cholesterol absorption and the maintenance of cholesterol homeostasis in the body. NPC1L1 is differentially expressed along the gastrointestinal tract with very low levels in the colon as compared with the small intestine. This study was undertaken to examine whether DNA methylation was responsible for segment-specific expression of NPC1L1. Treatment of mice with 5-azacytidine (i.p.) resulted in a significant dose-dependent increase in NPC1L1 mRNA expression in the colon. The lack of expression of NPC1L1 in the normal colon was associated with high levels of methylation in the area flanking the 3-kb fragment upstream of the initiation site of the mouse NPC1L1 gene in mouse colon as analyzed by EpiTYPER® MassARRAY®. The high level of methylation in the colon was observed in specific CpG dinucleotides and was significantly decreased in response to 5-azacytidine. Similar to mouse NPC1L1, 5-azacytidine treatment also increased the level of human NPC1L1 mRNA expression in the intestinal HuTu-80 cell line in a dose- and time-dependent manner. Silencing the expression of DNA methyltransferase DNMT1, -2, -3A, and -3B alone by siRNA did not affect NPC1L1 expression in HuTu-80 cells. However, the simultaneous attenuation of DNMT1 and -3B expression caused a significant increase in NPC1L1 mRNA expression as compared with control. Also, in vitro methylation of the human NPC1L1 promoter significantly decreased NPC1L1 promoter activity in human intestinal Caco2 cells. In conclusion, our data demonstrated for the first time that DNA methylation in the promoter region of the NPC1L1 gene appears to be a major mechanism underlying differential expression of NPC1L1 along the length of the gastrointestinal tract. PMID:24904062

  4. A low-power inverter-based CMOS level-crossing analog-to-digital converter for low-frequency biosignal sensing

    NASA Astrophysics Data System (ADS)

    Tanaka, Suiki; Niitsu, Kiichi; Nakazato, Kazuo

    2016-03-01

    Low-power analog-to-digital conversion is a key technique for power-limited biomedical applications such as power-limited continuous glucose monitoring. However, a conventional uniform-sampling analog-to-digital converter (ADC) is not suitable for nonuniform biosignals. A level-crossing ADC (LC-ADC) is a promising candidate for low-power biosignal processing because of its event-driven properties. The LC-ADC acquires data by level-crossing sampling. When an input signal crosses the threshold level, the LC-ADC samples the signal. The conventional LC-ADC employs a power-hungry comparator. In this paper, we present a low-power inverter-based LC-ADC. By adjusting the threshold level of the inverter, it can be used as a threshold-fixed window comparator. By using the inverter as an alternative to a comparator, power consumption can be markedly reduced. As a result, the total power consumption is successfully reduced by 90% of that of previous LC-ADC. The inverter-based LC-ADC was found to be very suitable for use in power-limited biomedical devices.

  5. Multilevel DC link inverter

    DOEpatents

    Su, Gui-Jia

    2003-06-10

    A multilevel DC link inverter and method for improving torque response and current regulation in permanent magnet motors and switched reluctance motors having a low inductance includes a plurality of voltage controlled cells connected in series for applying a resulting dc voltage comprised of one or more incremental dc voltages. The cells are provided with switches for increasing the resulting applied dc voltage as speed and back EMF increase, while limiting the voltage that is applied to the commutation switches to perform PWM or dc voltage stepping functions, so as to limit current ripple in the stator windings below an acceptable level, typically 5%. Several embodiments are disclosed including inverters using IGBT's, inverters using thyristors. All of the inverters are operable in both motoring and regenerating modes.

  6. A method for predicting the noise levels of coannular jets with inverted velocity profiles

    NASA Technical Reports Server (NTRS)

    Russell, J. W.

    1979-01-01

    A coannular jet was equated with a single stream equivalent jet with the same mass flow, energy, and thrust. The acoustic characteristics of the coannular jet were then related to the acoustic characteristics of the single jet. Forward flight effects were included by incorporating a forward exponent, a Doppler amplification factor, and a Strouhal frequency shift. Model test data, including 48 static cases and 22 wind tunnel cases, were used to evaluate the prediction method. For the static cases and the low forward velocity wind tunnel cases, the spectral mean square pressure correlation coefficients were generally greater than 90 percent, and the spectral sound pressure level standard deviation were generally less than 3 decibels. The correlation coefficient and the standard deviation were not affected by changes in equivalent jet velocity. Limitations of the prediction method are also presented.

  7. Inverted Barometer Contributions to Accelerated and Extreme Annual Mean Sea Level Changes Along the East Coast of North America

    NASA Astrophysics Data System (ADS)

    Piecuch, C. G.; Ponte, R. M.

    2015-12-01

    Recent works have interpreted accelerated and extreme sea level (SL) changes along the northeast coast of North America primarily in terms of dynamic changes related to the meridional overturning or coastal circulations. Isostatic changes related to surface atmospheric pressure loading —the inverted barometer (IB) effect— have been deemed relatively unimportant, but a comprehensive analysis of the IB effect has been lacking. In this work, we use five different atmospheric pressure products to analyze the influence of the IB effect on annual mean SL from tide gauge records. Consistently across all products, the IB effect accounts for about 50% of the magnitude of a recent extreme event of SL rise in 2009 along Atlantic Canada and New England. In fact, the unique nature of the event was largely a result of the extreme IB signal. Estimated IB effects also amount to about 10-30% of recent multidecadal SL accelerations over the Mid-Atlantic Bight and Southern New England. These findings reiterate the need for careful estimation of IB effects for studies that want to interpret observed SL in terms of dynamic ocean circulation changes.

  8. Structure of glycosylated NPC1 luminal domain C reveals insights into NPC2 and Ebola virus interactions.

    PubMed

    Zhao, Yuguang; Ren, Jingshan; Harlos, Karl; Stuart, David I

    2016-03-01

    Niemann-pick type C1 (NPC1) is an endo/lysosomal membrane protein involved in intracellular cholesterol trafficking, and its luminal domain C is an essential endosomal receptor for Ebola and Marburg viruses. We have determined the crystal structure of glycosylated NPC1 luminal domain C and find all seven possible sites are glycosylated. Mapping the disease mutations onto the glycosylated structure reveals a potential binding face for NPC2. Knowledge-based docking of NPC1 onto Ebola viral glycoprotein and sequence analysis of filovirus susceptible and refractory species reveals four critical residues, H418, Q421, F502 and F504, some or all of which are likely responsible for the species-specific susceptibility to the virus infection. PMID:26846330

  9. Capsaicin mediates apoptosis in human nasopharyngeal carcinoma NPC-TW 039 cells through mitochondrial depolarization and endoplasmic reticulum stress.

    PubMed

    Ip, S-W; Lan, S-H; Lu, H-F; Huang, A-C; Yang, J-S; Lin, J-P; Huang, H-Y; Lien, J-C; Ho, C-C; Chiu, C-F; Wood, Wg; Chung, J-G

    2012-06-01

    Capsaicin, a pungent compound found in hot chili peppers, has been reported to have antitumor activities in many human cancer cell lines, but the induction of precise apoptosis signaling pathway in human nasopharyngeal carcinoma (NPC) cells is unclear. Here, we investigated the molecular mechanisms of capsaicin-induced apoptosis in human NPC, NPC-TW 039, cells. Effects of capsaicin involved endoplasmic reticulum (ER) stress, caspase-3 activation and mitochondrial depolarization. Capsaicin-induced cytotoxic effects (cell death) through G0/G1 phase arrest and induction of apoptosis of NPC-TW 039 cells in a dose-dependent manner. Capsaicin treatment triggered ER stress by promoting the production of reactive oxygen species (ROS), increasing levels of inositol-requiring 1 enzyme (IRE1), growth arrest and DNA-damage-inducible 153 (GADD153) and glucose-regulated protein 78 (GRP78). Other effects included an increase in cytosolic Ca(2+), loss of the mitochondrial transmembrane potential (ΔΨ(m)), releases of cytochrome c and apoptosis-inducing factor (AIF), and activation of caspase-9 and -3. Furthermore, capsaicin induced increases in the ratio of Bax/Bcl-2 and abundance of apoptosis-related protein levels. These results suggest that ER stress- and mitochondria-mediated cell death is involved in capsaicin-induced apoptosis in NPC-TW 039 cells. PMID:21859781

  10. Simplified High-Power Inverter

    NASA Technical Reports Server (NTRS)

    Edwards, D. B.; Rippel, W. E.

    1984-01-01

    Solid-state inverter simplified by use of single gate-turnoff device (GTO) to commutate multiple silicon controlled rectifiers (SCR's). By eliminating conventional commutation circuitry, GTO reduces cost, size and weight. GTO commutation applicable to inverters of greater than 1-kilowatt capacity. Applications include emergency power, load leveling, drives for traction and stationary polyphase motors, and photovoltaic-power conditioning.

  11. Applications of cascade multilevel inverters.

    PubMed

    Peng, Fang-zen; Qian, Zhao-ming

    2003-01-01

    Cascade multilevel inverters have been developed for electric utility applications. A cascade M-level inverter consists of (M-1)/2 H-bridges in which each bridge's dc voltage is supported by its own dc capacitor. The new inverter can: (1) generate almost sinusoidal waveform voltage while only switching one time per fundamental cycle; (2) dispense with multi-pulse inverters' transformers used in conventional utility interfaces and static var compensators; (3) enables direct parallel or series transformer-less connection to medium- and high-voltage power systems. In short, the cascade inverter is much more efficient and suitable for utility applications than traditional multi-pulse and pulse width modulation (PWM) inverters. The authors have experimentally demonstrated the superiority of the new inverter for power supply, (hybrid) electric vehicle (EV) motor drive, reactive power (var) and harmonic compensation. This paper summarizes the features, feasibility, and control schemes of the cascade inverter for utility applications including utility interface of renewable energy, voltage regulation, var compensation, and harmonic filtering in power systems. Analytical, simulated, and experimental results demonstrated the superiority of the new inverters. PMID:14566981

  12. Over-expression of miR-10b in NPC patients: correlation with LMP1 and Twist1.

    PubMed

    Allaya, Nesrine; Khabir, Abdelmajid; Sallemi-Boudawara, Tahia; Sellami, Noura; Daoud, Jamel; Ghorbel, Abdelmonem; Frikha, Mounir; Gargouri, Ali; Mokdad-Gargouri, Raja; Ayadi, Wajdi

    2015-05-01

    Aberrant expression of miR-10b has been described in many cancers but remains unexplored in nasopharyngeal carcinoma (NPC). Therefore, we aimed to study the miR-10b expression level in 43 NPC biopsies collected from Tunisian patients and three NPC xenografts. Then, we investigated the correlation between miR-10b expression and its upstream regulators LMP1/Twist1 as well as its adjacent gene HoxD4. We showed that miR-10b was significantly up-regulated in NPC biopsies compared to non-tumor nasopharyngeal tissues (fold change 153; p = 0.004) and associated with advanced clinical stage and young age at diagnosis (p = 0.005 and p = 0.011, respectively). In addition, over-expression of miR-10b was positively associated with the transcription factor Twist1 as well as the EBV oncoprotein LMP1 (fold change 6.32; p = 0.014, fold change 6.58; p = 0.01 respectively). Furthermore, higher level of miR-10b was observed in tumors with simultaneous expression of LMP1 and Twist1, compared to those expressing only Twist1 (fold change 2.49; p = 0.033). Meanwhile, the analysis of the link between miR-10b and its neighbor gene HoxD4 did not show any significant correlation (Fisher test p = 0.205; Mann-Whitney test p = 0.676). This study reports the first evidence of miR-10b over-expression in NPC patients. Furthermore, our findings can support hsa-miR-10b gene regulation through LMP1/Twist1 in NPC malignancy. PMID:25597482

  13. Ebolavirus Glycoprotein Directs Fusion through NPC1+ Endolysosomes

    PubMed Central

    Simmons, James A.; D'Souza, Ryan S.; Ruas, Margarida; Galione, Antony; Casanova, James E.

    2015-01-01

    Ebolavirus, a deadly hemorrhagic fever virus, was thought to enter cells through endolysosomes harboring its glycoprotein receptor, Niemann-Pick C1. However, an alternate model was recently proposed in which ebolavirus enters through a later NPC1-negative endosome that contains two-pore Ca2+ channel 2 (TPC2), a newly identified ebolavirus entry factor. Here, using live cell imaging, we obtained evidence that in contrast to the new model, ebolavirus enters cells through endolysosomes that contain both NPC1 and TPC2. PMID:26468524

  14. Segmentation of nasopharyngeal carcinoma (NPC) lesions in MR images

    SciTech Connect

    Lee, Francis K.H. . E-mail: fkhlee@cuhk.edu.hk; Yeung, David K.W.; King, Ann D.; Leung, S.F.; Ahuja, Anil

    2005-02-01

    Purpose: An accurate and reproducible method to delineate tumor margins from uninvolved tissues is of vital importance in guiding radiation therapy (RT). In nasopharyngeal carcinoma (NPC), tumor margin may be difficult to identify in magnetic resonance (MR) images, making the task of optimizing RT treatment more difficult. Our aim in this study is to develop a semiautomatic image segmentation method for NPC that requires minimal human intervention and is capable of delineating tumor margins with good accuracy and reproducibility. Methods and materials: The segmentation algorithm includes 5 stages: masking, Bayesian probability calculation, smoothing, thresholding and seed growing, and finally dilation and overlaying of results with different thresholds. The algorithm is based on information obtained from the contrast enhancement ratio of T1-weighted images and signal intensity of T2-weighted images. The algorithm is initiated by the selection of a valid anatomical seed point within the tumor by the user. The algorithm was evaluated on MR images from 7 NPC patients and was compared against the radiologist's reference outline. Results: The algorithm was successfully implemented on all 7 subjects. With a threshold of 1, the average percent match is 78.5 {+-} 3.86 (standard deviation) %, and the correspondence ratio is 66.5 {+-} 7%. Discussion: The segmentation algorithm presented here may be useful for diagnosing NPC and may guide RT treatment planning. Further improvement will be desirable to improve the accuracy and versatility of the method.

  15. Quantitative Proteomics of Human Fibroblasts with I1061T Mutation in Niemann–Pick C1 (NPC1) Protein Provides Insights into the Disease Pathogenesis*

    PubMed Central

    Rauniyar, Navin; Subramanian, Kanagaraj; Lavallée-Adam, Mathieu; Martínez-Bartolomé, Salvador; Balch, William E.; Yates, John R.

    2015-01-01

    Niemann-Pick type C (NPC) disease is a fatal neurodegenerative disorder characterized by the accumulation of unesterified cholesterol in the late endosomal/lysosomal compartments. Mutations in the NPC1 protein are implicated in 95% of patients with NPC disease. The most prevalent mutation is the missense mutation I1061T that occurs in ∼15–20% of the disease alleles. In our study, an isobaric labeling-based quantitative analysis of proteome of NPC1I1061T primary fibroblasts when compared with wild-type cells identified 281 differentially expressed proteins based on stringent data analysis criteria. Gene ontology enrichment analysis revealed that these proteins play important roles in diverse cellular processes such as protein maturation, energy metabolism, metabolism of reactive oxygen species, antioxidant activity, steroid metabolism, lipid localization, and apoptosis. The relative expression level of a subset of differentially expressed proteins (TOR4A, DHCR24, CLGN, SOD2, CHORDC1, HSPB7, and GAA) was independently and successfully substantiated by Western blotting. We observed that treating NPC1I1061T cells with four classes of seven different compounds that are potential NPC drugs increased the expression level of SOD2 and DHCR24. We have also shown an abnormal accumulation of glycogen in NPC1I1061T fibroblasts possibly triggered by defective processing of lysosomal alpha-glucosidase. Our study provides a starting point for future more focused investigations to better understand the mechanisms by which the reported dysregulated proteins triggers the pathological cascade in NPC, and furthermore, their effect upon therapeutic interventions. PMID:25873482

  16. Overload protection system for power inverter

    NASA Technical Reports Server (NTRS)

    Nagano, S. (Inventor)

    1977-01-01

    An overload protection system for a power inverter utilized a first circuit for monitoring current to the load from the power inverter to detect an overload and a control circuit to shut off the power inverter, when an overload condition was detected. At the same time, a monitoring current inverter was turned on to deliver current to the load at a very low power level. A second circuit monitored current to the load, from the monitoring current inverter, to hold the power inverter off through the control circuit, until the overload condition was cleared so that the control circuit may be deactivated in order for the power inverter to be restored after the monitoring current inverter is turned off completely.

  17. Stream, Inverted

    NASA Technical Reports Server (NTRS)

    2006-01-01

    27 July 2006 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows the inverted, eroded remains of a channel -- now standing as a complex ridge that runs across the middle of this scene -- in dust-mantled terrain west of Sinus Meridiani, Mars. The original channel might have been carved by running water, but too little detail remains today to provide any certainty as to whether water was the culprit.

    Location near: 5.6oN, 7.6oW Image width: 3 km (1.9 mi) Illumination from: upper left Season: Northern Spring

  18. Power inverters

    SciTech Connect

    Miller, David H.; Korich, Mark D.; Smith, Gregory S.

    2011-11-15

    Power inverters include a frame and a power module. The frame has a sidewall including an opening and defining a fluid passageway. The power module is coupled to the frame over the opening and includes a substrate, die, and an encasement. The substrate includes a first side, a second side, a center, an outer periphery, and an outer edge, and the first side of the substrate comprises a first outer layer including a metal material. The die are positioned in the substrate center and are coupled to the substrate first side. The encasement is molded over the outer periphery on the substrate first side, the substrate second side, and the substrate outer edge and around the die. The encasement, coupled to the substrate, forms a seal with the metal material. The second side of the substrate is positioned to directly contact a fluid flowing through the fluid passageway.

  19. Ryanodine receptor antagonists adapt NPC1 proteostasis to ameliorate lipid storage in Niemann-Pick type C disease fibroblasts.

    PubMed

    Yu, Ting; Chung, Chan; Shen, Dongbiao; Xu, Haoxing; Lieberman, Andrew P

    2012-07-15

    Niemann-Pick type C disease is a lysosomal storage disorder most often caused by loss-of-function mutations in the NPC1 gene. The encoded multipass transmembrane protein is required for cholesterol efflux from late endosomes and lysosomes. Numerous missense mutations in the NPC1 gene cause disease, including the prevalent I1061T mutation that leads to protein misfolding and degradation. Here, we sought to modulate the cellular proteostasis machinery to achieve functional recovery in primary patient fibroblasts. We demonstrate that targeting endoplasmic reticulum (ER) calcium levels using ryanodine receptor (RyR) antagonists increased steady-state levels of the NPC1 I1061T protein. These compounds also promoted trafficking of mutant NPC1 to late endosomes and lysosomes and rescued the aberrant storage of cholesterol and sphingolipids that is characteristic of disease. Similar rescue was obtained using three distinct RyR antagonists in cells with missense alleles, but not with null alleles, or by over-expressing calnexin, a calcium-dependent ER chaperone. Our work highlights the utility of proteostasis regulators to remodel the protein-folding environment in the ER to recover function in the setting of disease-causing missense alleles. PMID:22505584

  20. The c.-133A > G polymorphism in NPC1L1 gene influences the efficacy of ezetimibe monotherapy on apolipoprotein A1 in hyperlipidemic patients.

    PubMed

    Zsíros, N; Bodor, M; Varga, V; Berta, E; Balogh, I; Seres, I; Paragh, G; Harangi, M

    2014-06-01

    Niemann-Pick C1-like 1 protein (NPC1L1) plays a critical role in intestinal cholesterol absorption. Previous studies found that the NPC1L1 c.-133A > G SNP, but not other NPC1L1 SNPs, was associated with response to statin treatment and statin-ezetimibe combinations. To date effect of NPC1L1 c.-133A > G SNP on ezetimibe monotherapy has not been studied. Our objective was to examine whether SNP c.-133A > G at the NPC1L1 gene has effects on lipid levels and on the efficacy of 3, 6 and 12 months of 10 mg daily ezetimibe monotherapy in hyperlipidemic patients with statin induced adverse effects. One hundred and one type IIa and IIb hyperlipidemic patients (72 females, 29 males; age: 61.23 +/- 9.87 ys; BMI: 28.18 +/- 4.29 kg/m2) were enrolled. The genotype frequencies were conformed to Hardy-Weinberg equilibrium. We could not find significant differences in initial lipid levels between AA and AG + GG patients. While plasma levels of apolipoprotein A1 (ApoA1) did not significantly decrease after ezetimibe treatment (1.96; 3.39 and 2.74%) in AA patients, a significant elevation in ApoA1 levels has been found after treatment in AG + GG patients (9.15; 8.54 and 13.58%). The effect of NPC1L1 c.-133A > G on the ApoA1 levels was found significant (p < 0.05). Efficacy of treatment with ezetimibe on other plasma lipid parameters after 3, 6 or 12 months did not differ significantly. NPC1L1-133A > G SNP influences the ApoA1 response to ezetimibe monotherapy, therefore, may alter the effect of ezetimibe on the structure and function of the high-density lipoprotein particles. PMID:24974575

  1. NPC1L1 is a key regulator of intestinal vitamin K absorption and a modulator of warfarin therapy.

    PubMed

    Takada, Tappei; Yamanashi, Yoshihide; Konishi, Kentaro; Yamamoto, Takehito; Toyoda, Yu; Masuo, Yusuke; Yamamoto, Hideaki; Suzuki, Hiroshi

    2015-02-18

    Vitamin K (VK) is a micronutrient that facilitates blood coagulation. VK antagonists, such as warfarin, are used in the clinic to prevent thromboembolism. Because VK is not synthesized in the body, its intestinal absorption is crucial for maintaining whole-body VK levels. However, the molecular mechanism of this absorption is unclear. We demonstrate that Niemann-Pick C1-like 1 (NPC1L1) protein, a cholesterol transporter, plays a central role in intestinal VK uptake and modulates the anticoagulant effect of warfarin. In vitro studies using NPC1L1-overexpressing intestinal cells and in vivo studies with Npc1l1-knockout mice revealed that intestinal VK absorption is NPC1L1-dependent and inhibited by ezetimibe, an NPC1L1-selective inhibitor clinically used for dyslipidemia. In addition, in vivo pharmacological studies demonstrated that the coadministration of ezetimibe and warfarin caused a reduction in hepatic VK levels and enhanced the pharmacological effect of warfarin. Adverse events caused by the coadministration of ezetimibe and warfarin were rescued by oral VK supplementation, suggesting that the drug-drug interaction effects observed were the consequence of ezetimibe-mediated VK malabsorption. This mechanism was supported by a retrospective evaluation of clinical data showing that, in more than 85% of warfarin-treated patients, the anticoagulant activity was enhanced by cotreatment with ezetimibe. Our findings provide insight into the molecular mechanism of VK absorption. This new drug-drug interaction mechanism between ezetimibe (a cholesterol transport inhibitor) and warfarin (a VK antagonist and anticoagulant) could inform clinical care of patients on these medications, such as by altering the kinetics of essential, fat-soluble vitamins. PMID:25696002

  2. c-Src activation promotes nasopharyngeal carcinoma metastasis by inducing the epithelial-mesenchymal transition via PI3K/Akt signaling pathway: a new and promising target for NPC.

    PubMed

    Ke, Liangru; Xiang, Yanqun; Guo, Xiang; Lu, Jinping; Xia, Weixiong; Yu, Yahui; Peng, Yongjian; Wang, Li; Wang, Gang; Ye, Yanfang; Yang, Jing; Liang, Hu; Kang, Tiebang; Lv, Xing

    2016-05-10

    Aberrant activation of cellular Src (c-Src), a non-receptor tyrosine kinase, could promote cancer progression through activating its downstream signaling pathways. However, the roles of c-Src and phosphorylated-Src (p-Src) in nasopharyngeal carcinoma (NPC) progression are rarely investigated. Herein, we have identified high c-Src concentrations in the serum of NPC patients with distant metastasis using high-throughput protein microarrays. Levels of c-Src in serum and p-Src in human primary NPC samples were unfavorable independent prognostic factors for cancer-specific survival, disease-free survival, and distant metastasis-free survival. Depletion or inactivation of c-Src in NPC cells using sgRNA with CRISPR/Cas9 system or PP2 decreased cell viability, colony formation, migration and invasion in vitro and metastasis in vivo. In contrast, these malignancies could be up-regulated by overexpressed c-Src in a NPC cell line with low-metastasis potential. Furthermore, p-Src was involved in promoting NPC cell metastasis by inducing the epithelial-mesenchymal transition (EMT) process via activating the PI3K/Akt pathway and cytoskeleton remodeling. The p-Src-induced EMT process could be retarded by PP2, which mediated by down-regulating the PI3K/Akt pathway. In conclusion, elevated levels of c-Src in serum and p-Src in primary NPC tissue correlated with poor outcomes of NPC patients. And aberrant activation of c-Src facilitated NPC cells with malignant potential, especially metastasis ability, which mediated by the PI3K/Akt pathway activation and sequentially induced the EMT process. These findings unveiled a promising approach for targeted therapy of advanced NPC. PMID:27078847

  3. Ezetimibe-sensitive cholesterol uptake by NPC1L1 protein does not require endocytosis

    PubMed Central

    Johnson, Tory A.; Pfeffer, Suzanne R.

    2016-01-01

    Human NPC1L1 protein mediates cholesterol absorption in the intestine and liver and is the target of the drug ezetimibe, which is used to treat hypercholesterolemia. Previous studies concluded that NPC1L1-GFP protein trafficking is regulated by cholesterol binding and that ezetimibe blocks NPC1L1-GFP function by inhibiting its endocytosis. We used cell surface biotinylation to monitor NPC1L1-GFP endocytosis and show that ezetimibe does not alter the rate of NPC1L1-GFP endocytosis in cultured rat hepatocytes grown under normal growth conditions. As expected, NPC1L1-GFP endocytosis depends in part on C-terminal, cytoplasmically oriented sequences, but endocytosis does not require cholesterol binding to NPC1L1’s N-terminal domain. In addition, two small- molecule inhibitors of general (and NPC1L1-GFP) endocytosis failed to inhibit the ezetimibe-sensitive uptake of [3H]cholesterol from taurocholate micelles. These experiments demonstrate that cholesterol uptake by NPC1L1 does not require endocytosis; moreover, ezetimibe interferes with NPC1L1’s cholesterol adsorption activity without blocking NPC1L1 internalization in RH7777 cells. PMID:27075173

  4. Ezetimibe-sensitive cholesterol uptake by NPC1L1 protein does not require endocytosis.

    PubMed

    Johnson, Tory A; Pfeffer, Suzanne R

    2016-06-01

    Human NPC1L1 protein mediates cholesterol absorption in the intestine and liver and is the target of the drug ezetimibe, which is used to treat hypercholesterolemia. Previous studies concluded that NPC1L1-GFP protein trafficking is regulated by cholesterol binding and that ezetimibe blocks NPC1L1-GFP function by inhibiting its endocytosis. We used cell surface biotinylation to monitor NPC1L1-GFP endocytosis and show that ezetimibe does not alter the rate of NPC1L1-GFP endocytosis in cultured rat hepatocytes grown under normal growth conditions. As expected, NPC1L1-GFP endocytosis depends in part on C-terminal, cytoplasmically oriented sequences, but endocytosis does not require cholesterol binding to NPC1L1's N-terminal domain. In addition, two small- molecule inhibitors of general (and NPC1L1-GFP) endocytosis failed to inhibit the ezetimibe-sensitive uptake of [(3)H]cholesterol from taurocholate micelles. These experiments demonstrate that cholesterol uptake by NPC1L1 does not require endocytosis; moreover, ezetimibe interferes with NPC1L1's cholesterol adsorption activity without blocking NPC1L1 internalization in RH7777 cells. PMID:27075173

  5. 2.3-MW Medium-Voltage, Three-Level Wind Energy Inverter Applying a Unique Bus Structure and 4.5-kV Si/SiC Hybrid Isolated Power Modules: Preprint

    SciTech Connect

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

    2014-11-01

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

  6. NREL Pyrheliometer Comparisons: September 22-26, 2014 (NPC-2014)

    SciTech Connect

    Reda, I.; Dooraghi, M.; Habte, A.

    2014-10-01

    Accurate measurements of direct normal (beam) solar irradiance from pyrheliometers are important for developing and deploying solar energy conversion systems, improving our understanding of the Earth's energy budget for climate change studies, and for other science and technology applications involving solar flux. Providing these measurements places many demands on the quality system used by the operator of commercially available radiometers. Maintaining accurate radiometer calibrations that are traceable to an international standard is the first step in producing research-quality solar irradiance measurements. As with all measurement systems, absolute cavity radiometers and other types of pyrheliometers are subject to performance changes over time. NREL has developed and maintained a select group of absolute cavity radiometers with direct calibration traceability to the World Radiometric Reference (WRR), and uses these reference instruments to calibrate pyrheliometers and pyranometers using the ISO 17025 accredited Broadband Outdoor Radiometer Calibration (BORCAL) process. National Renewable Energy Laboratory (NREL) pyrheliometer comparisons (NPCs) are held annually at the Solar Radiation Research Laboratory (SRRL) in Golden, Colorado. Open to all pyrheliometer owners and operators, each NPC provides an opportunity to determine the unique WRR transfer factor (WRR-TF) for each participating pyrheliometer. By adjusting all subsequent pyrheliometer measurements by the appropriate WRR-TF, the solar irradiance data are traceable to the WRR. NPC-2014 was held September 22-26, 2014. Participants operated 36 absolute cavity radiometers and 22 conventional thermopile-based pyrheliometers to simultaneously measure clear-sky direct normal solar irradiance during this period, and this report documents the findings.

  7. Potential effects of NPC1L1 polymorphisms in protecting against clinical disease in a chinese family with sitosterolaemia.

    PubMed

    Hu, Miao; Yuen, Yuet-Ping; Kwok, Jeffrey Ss; Griffith, James F; Tomlinson, Brian

    2014-01-01

    Sitosterolaemia is caused by mutations in either ABCG5 or ABCG8. Chinese and Japanese individuals usually have mutations in ABCG5. We herein report a known and a novel mutation in ABCG8 and their potential interaction with NPC1L1 polymorphisms in a Chinese family with sitosterolaemia. We sequenced ABCG5 and ABCG8 and measured the levels of plasma plant sterols in a 15-year-old Chinese girl with clinical sitosterolaemia (xanthomas with elevated low-density lipoprotein cholesterol (LDL-C) and plant sterols) and her apparently healthy family members. NPC1L1 was sequenced in the genetically affected sibling and other family members. A known mutation, c.490C>T (p. Arg164(*)), in exon 4 and a novel mutation, c.1949T>G (p.Leu650Arg), in exon 13 of ABCG8 were detected in the proband and her sister, who had elevated sterols but low LDL-C levels and no xanthomas. The genetically affected sister, but not the proband, carried two additional heterozygous changes in NPC1L1 (rs2072183 C>G, rs2301935 A>C), which were inherited from the mother, who also had a low LDL-C level. In this study, we detected a known and a novel mutation in ABCG8 in a Chinese patient with sitosterolaemia. The same mutations were found in her clinically normal sister, suggesting that the contrasting features with the proband may be related to different variants in NPC1L1 and/or some other undetermined lipid-related genetic factors. PMID:25056759

  8. Structure of N-Terminal Domain of NPC1 Reveals Distinct Subdomains for Binding and Transfer of Cholesterol

    SciTech Connect

    Kwon, Hyock Joo; Abi-Mosleh, Lina; Wang, Michael L.; Deisenhofer, Johann; Goldstein, Joseph L.; Brown, Michael S.; Infante, Rodney E.

    2010-09-21

    LDL delivers cholesterol to lysosomes by receptor-mediated endocytosis. Exit of cholesterol from lysosomes requires two proteins, membrane-bound Niemann-Pick C1 (NPC1) and soluble NPC2. NPC2 binds cholesterol with its isooctyl side chain buried and its 3{beta}-hydroxyl exposed. Here, we describe high-resolution structures of the N-terminal domain (NTD) of NPC1 and complexes with cholesterol and 25-hydroxycholesterol. NPC1(NTD) binds cholesterol in an orientation opposite to NPC2: 3{beta}-hydroxyl buried and isooctyl side chain exposed. Cholesterol transfer from NPC2 to NPC1(NTD) requires reorientation of a helical subdomain in NPC1(NTD), enlarging the opening for cholesterol entry. NPC1 with point mutations in this subdomain (distinct from the binding subdomain) cannot accept cholesterol from NPC2 and cannot restore cholesterol exit from lysosomes in NPC1-deficient cells. We propose a working model wherein after lysosomal hydrolysis of LDL-cholesteryl esters, cholesterol binds NPC2, which transfers it to NPC1(NTD), reversing its orientation and allowing insertion of its isooctyl side chain into the outer lysosomal membranes.

  9. Npc1 is involved in sterol trafficking in the filamentous fungus Fusarium graminearum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The ortholog of the human gene NPC1 was identified in the plant pathogenic, filamentous fungus Fusarium graminearum by shared amino acid sequence, protein domain structure and cellular localization of the mature fungal protein. The Fusarium Npc1 gene shares 34% amino acid sequence identity and 51% s...

  10. Filovirus receptor NPC1 contributes to species-specific patterns of ebolavirus susceptibility in bats.

    PubMed

    Ng, Melinda; Ndungo, Esther; Kaczmarek, Maria E; Herbert, Andrew S; Binger, Tabea; Kuehne, Ana I; Jangra, Rohit K; Hawkins, John A; Gifford, Robert J; Biswas, Rohan; Demogines, Ann; James, Rebekah M; Yu, Meng; Brummelkamp, Thijn R; Drosten, Christian; Wang, Lin-Fa; Kuhn, Jens H; Müller, Marcel A; Dye, John M; Sawyer, Sara L; Chandran, Kartik

    2015-01-01

    Biological factors that influence the host range and spillover of Ebola virus (EBOV) and other filoviruses remain enigmatic. While filoviruses infect diverse mammalian cell lines, we report that cells from African straw-colored fruit bats (Eidolon helvum) are refractory to EBOV infection. This could be explained by a single amino acid change in the filovirus receptor, NPC1, which greatly reduces the affinity of EBOV-NPC1 interaction. We found signatures of positive selection in bat NPC1 concentrated at the virus-receptor interface, with the strongest signal at the same residue that controls EBOV infection in Eidolon helvum cells. Our work identifies NPC1 as a genetic determinant of filovirus susceptibility in bats, and suggests that some NPC1 variations reflect host adaptations to reduce filovirus replication and virulence. A single viral mutation afforded escape from receptor control, revealing a pathway for compensatory viral evolution and a potential avenue for expansion of filovirus host range in nature. PMID:26698106

  11. Experimental identification and characterization of 97 novel npcRNA candidates in Salmonella enterica serovar Typhi

    PubMed Central

    Chinni, Suresh V.; Raabe, Carsten A.; Zakaria, Robaiza; Randau, Gerrit; Hoe, Chee Hock; Zemann, Anja; Brosius, Juergen; Tang, Thean-Hock; Rozhdestvensky, Timofey S.

    2010-01-01

    We experimentally identified and characterized 97 novel, non-protein-coding RNA candidates (npcRNAs) from the human pathogen Salmonella enterica serovar Typhi (hereafter referred to as S. typhi). Three were specific to S. typhi, 22 were restricted to Salmonella species and 33 were differentially expressed during S. typhi growth. We also identified Salmonella Pathogenicity Island-derived npcRNAs that might be involved in regulatory mechanisms of virulence, antibiotic resistance and pathogenic specificity of S. typhi. An in-depth characterization of S. typhi StyR-3 npcRNA showed that it specifically interacts with RamR, the transcriptional repressor of the ramA gene, which is involved in the multidrug resistance (MDR) of Salmonella. StyR-3 interfered with RamR–DNA binding activity and thus potentially plays a role in regulating ramA gene expression, resulting in the MDR phenotype. Our study also revealed a large number of cis-encoded antisense npcRNA candidates, supporting previous observations of global sense–antisense regulatory networks in bacteria. Finally, at least six of the npcRNA candidates interacted with the S. typhi Hfq protein, supporting an important role of Hfq in npcRNA networks. This study points to novel functional npcRNA candidates potentially involved in various regulatory roles including the pathogenicity of S. typhi. PMID:20460466

  12. EBV reactivation as a target of luteolin to repress NPC tumorigenesis

    PubMed Central

    Wu, Chung-Chun; Fang, Chih-Yeu; Hsu, Hui-Yu; Chuang, Hsin-Ying; Cheng, Yu-Jhen; Chen, Yen-Ju; Chou, Sheng-Ping; Huang, Sheng-Yen; Lin, Su-Fang; Chang, Yao; Tsai, Ching-Hwa; Chen, Jen-Yang

    2016-01-01

    Nasopharyngeal carcinoma (NPC) is a malignancy derived from the epithelial cells of the nasopharynx. Although a combination of radiotherapy with chemotherapy is effective for therapy, relapse and metastasis after remission remain major causes of mortality. Epstein-Barr virus (EBV) is believed to be one of causes of NPC development. We demonstrated previously that EBV reactivation is important for the carcinogenesis of NPC. We sought, therefore, to determine whether EBV reactivation can be a target for retardation of relapse of NPC. After screening, we found luteolin is able to inhibit EBV reactivation. It inhibited EBV lytic protein expression and repressed the promoter activities of two major immediate-early genes, Zta and Rta. Furthermore, luteolin was shown to reduce genomic instability induced by recurrent EBV reactivation in NPC cells. EBV reactivation-induced NPC cell proliferation and migration, as well as matrigel invasiveness, were also repressed by luteolin treatment. Tumorigenicity in mice, induced by EBV reactivation, was decreased profoundly following luteolin administration. Together, these results suggest that inhibition of EBV reactivation is a novel approach to prevent the relapse of NPC. PMID:26967558

  13. PHIL Inverter Test Report: Analysis of High-Penetration Levels of PV into the Distribution Grid in California, March 12 - March 16, 2012

    SciTech Connect

    Kromer, M.

    2013-06-01

    This report describes power hardware-in-the-loop simulation testing of a 500 kW Satcon photovoltaic inverter, conducted at the Center for Advanced Power Systems at Florida State University from March 12th through March 16th, 2012. Testing was led by a team from the National Renewable Energy Laboratory. The report reviews the results of data captured during the course of testing. The tests were used to demonstrate operation of and gather data from the inverter in a simulated operational environment. Testing demonstrated the ability of the inverter to operate in either a Power Factor Control Mode or a Reactive Power Command Mode, and to respond to real power limits.

  14. NREL Pyrheliometer Comparison: September 16 to 27, 2013 (NPC-2013)

    SciTech Connect

    Reda, I.; Dooraghi, M.; Habte, A.

    2013-11-01

    Accurate measurements of direct normal (beam) solar irradiance from pyrheliometers are important for the development and deployment of solar energy conversion systems, improving our understanding of the Earth's energy budget for climate change studies, and for other science and technology applications involving solar flux. Providing these measurements places many demands on the quality system used by the operator of commercially available radiometers. Maintaining accurate radiometer calibrations traceable to an international standard is the first step in producing research-quality solar irradiance measurements. As with all measurement systems, absolute cavity radiometers and other types of pyrheliometers are subject to performance changes over time. NREL has developed and maintained a group of absolute cavity radiometers with direct calibration traceability to the World Radiometric Reference (WRR). These reference instruments are used by NREL to calibrate pyrheliometers and pyranometers using the ISO 17025 accredited Broadband Outdoor Radiometer Calibration (BORCAL) process (Reda et al. 2008). NPCs are held annually at the Solar Radiation Research Laboratory (SRRL) in Golden, Colorado. Open to all pyrheliometer owners/operators, e.g. NREL, NASA, NIST, NOAA, USA industry and academia, USA-DOE and other national laboratories, and national and international organizations. Each NPC provides an opportunity to determine the unique World Radiometric Reference (WRR) transfer factor (WRR-TF) for each participating pyrheliometer. By adjusting all subsequent pyrheliometer measurements by the appropriate WRR-TF, the solar irradiance data are traceable to the International System of Units through WRR.

  15. Understanding the interplay between host immunity and Epstein-Barr virus in NPC patients

    PubMed Central

    Shen, Yong; Zhang, Suzhan; Sun, Ren; Wu, Tingting; Qian, Jing

    2015-01-01

    Epstein-Barr virus (EBV) has been used as a paradigm for studying host–virus interactions, not only because of its importance as a human oncogenic virus associated with several malignancies including nasopharyngeal carcinoma (NPC) but also owing to its sophisticated strategies to subvert the host antiviral responses. An understanding of the interplay between EBV and NPC is critical for the development of EBV-targeted immunotherapy. Here, we summarize the current knowledge regarding the host immune responses and EBV immune evasion mechanisms in the context of NPC. PMID:26038769

  16. Switching Characteristics of Ferroelectric Transistor Inverters

    NASA Technical Reports Server (NTRS)

    Laws, Crystal; Mitchell, Coey; MacLeod, Todd C.; Ho, Fat D.

    2010-01-01

    This paper presents the switching characteristics of an inverter circuit using a ferroelectric field effect transistor, FeFET. The propagation delay time characteristics, phl and plh are presented along with the output voltage rise and fall times, rise and fall. The propagation delay is the time-delay between the V50% transitions of the input and output voltages. The rise and fall times are the times required for the output voltages to transition between the voltage levels V10% and V90%. Comparisons are made between the MOSFET inverter and the ferroelectric transistor inverter.

  17. NREL Pyrheliometer Comparisons (NPC-2001), September 24 - October 5, 2001, Golden, Colorado

    SciTech Connect

    Reda, I.; Stoffel, T.; Wilcox, S.

    2003-09-01

    NREL Pyrheliometer Comparisons (NPCs) are held annually at the Solar Radiation Research Laboratory (SRRL) in Golden, Colorado. Open to all pyrheliometer owner/operators, the NPC provides an opportunity to determine the unique WRR transfer factor for each participating pyrheliometer.

  18. NREL Pyrheliometer Comparisons (NPC-2003), September 22 - October 3, 2003, Golden, Colorado

    SciTech Connect

    Stoffel, T.; Reda, I.; Wilcox, S.

    2004-07-01

    NREL Pyrheliometer Comparisons (NPCs) are held annually at the Solar Radiation Research Laboratory (SRRL) in Golden, Colorado. Open to all pyrheliometer owner/operators, the NPC provides an opportunity to determine the unique WRR transfer factor for each participating pyrheliometer.

  19. Results of NREL Pyrheliometer Comparisons (NPC1999), October 4-10, 1999, Golden, Colorado

    SciTech Connect

    Reda, I.; Stoffel, T.; Wilcox, S.

    2000-09-01

    NREL Pyrheliometer Comparisons (NPCs) are held annually at the Solar Radiation Research Laboratory (SRRL) in Golden, Colorado. Open to all pyrheliometer owner/operators, the NPC provides an opportunity to determine the unique WRR transfer factor for each participating pyrheliometer.

  20. NREL Pyrheliometer Comparisons (NPC-2002), September 23 - October 4, 2002, Golden, Colorado

    SciTech Connect

    Reda, I.; Stoffel, T.; Wilcox, S.

    2003-09-01

    NREL Pyrheliometer Comparisons (NPCs) are held annually at the Solar Radiation Research Laboratory (SRRL) in Golden, Colorado. Open to all pyrheliometer owner/operators, the NPC provides an opportunity to determine the unique WRR transfer factor for each participating pyrheliometer.

  1. Integrated Inverter And Battery Charger

    NASA Technical Reports Server (NTRS)

    Rippel, Wally E.

    1988-01-01

    Circuit combines functions of dc-to-ac inversion (for driving ac motor in battery-powered vehicle) and ac-to-dc conversion (for charging battery from ac line when vehicle not in use). Automatically adapts to either mode. Design of integrated inverter/charger eliminates need for duplicate components, saves space, reduces weight and cost of vehicle. Advantages in other applications : load-leveling systems, standby ac power systems, and uninterruptible power supplies.

  2. Stepped sinewave inverter

    NASA Astrophysics Data System (ADS)

    Appelbaum, J.; Gabbay, D.

    1984-11-01

    A stepped sinewave dc/ac inverter was analyzed for an inductive load with respect to load current and voltage, harmonics, power factor, and efficiency. This special inverter of high efficiency and low harmonic content is constructed by synthesizing the sinusoidal output by discrete voltage sources, such as storage batteries, solar cell, etc., with electronic switching of the sources at specific time intervals. The switching times are determined for the condition of minimum distortion of the synthesized wave. A 50 W inverter was built and tested to demonstrate this approach.

  3. Subversion of NPC1 pathway of cholesterol transport by Anaplasma phagocytophilum

    PubMed Central

    Xiong, Qingming; Rikihisa, Yasuko

    2013-01-01

    Summary Intracellular cholesterol amounts, distribution, and traffic are tightly regulated to maintain the healthy eukaryotic cell function. However, how intracellular pathogens that require cholesterol, interact with the host cholesterol homeostasis and traffic is not well understood. Anaplasma phagocytophilum is an obligatory intracellular and cholesterol-robbing bacterium, which causes human granulocytic anaplasmosis. Here we found that a subset of cholesterol-binding membrane protein, Niemann–Pick type C1 (NPC1)-bearing vesicles devoid of lysosomal markers were upregulated in HL-60 cells infected with A. phagocytophilum, and trafficked to live bacterial inclusions. The NPC1 localization to A. phagocytophilum inclusions was abolished by low-density lipoprotein (LDL)-derived cholesterol traffic inhibitor U18666A. Studies using NPC1 siRNA and the cell line with cholesterol traffic defect demonstrated that the NPC1 function is required for bacterial cholesterol acquisition and infection. Furthermore, trans-Golgi network-specific soluble N-ethylmaleimide-sensitive factor attachment protein receptors, vesicle-associated membrane protein (VAMP4) and syntaxin 16, which are associated with NPC1 and LDL-derived cholesterol vesicular transport were recruited to A. phagocytophilum inclusions, and VAMP4 was required for bacteria infection. Taken together, A. phagocytophilum is the first example of a pathogen that subverts the NPC1 pathway of intracellular cholesterol transport and homeostasis for bacterial inclusion membrane biogenesis and cholesterol capture. PMID:22212234

  4. Inhibiting intestinal NPC1L1 activity prevents diet-induced increase in biliary cholesterol in Golden Syrian hamsters.

    PubMed

    Valasek, Mark A; Repa, Joyce J; Quan, Gang; Dietschy, John M; Turley, Stephen D

    2008-10-01

    Niemann-Pick C1-like 1 (NPC1L1) facilitates the uptake of sterols into the enterocyte and is the target of the novel cholesterol absorption inhibitor, ezetimibe. These studies used the Golden Syrian hamster as a model to delineate the changes in the relative mRNA expression of NPC1L1 and other proteins that regulate sterol homeostasis in the enterocyte during and following cessation of ezetimibe treatment and also to address the clinically important question of whether the marked inhibition of cholesterol absorption alters biliary lipid composition. In hamsters fed a low-cholesterol, low-fat basal diet, the abundance of mRNA for NPC1L1 in the small intestine far exceeded that in other regions of the gastrointestinal tract, liver, and gallbladder. In the first study, female hamsters were fed the basal diet containing ezetimibe at doses up to 2.0 mg.day(-1).kg body wt(-1). At this dose, cholesterol absorption fell by 82%, fecal neutral sterol excretion increased by 5.3-fold, and hepatic and intestinal cholesterol synthesis increased more than twofold, but there were no significant changes in either fecal bile acid excretion or biliary lipid composition. The ezetimibe-induced changes in intestinal cholesterol handling were reversed when treatment was withdrawn. In a second study, male hamsters were given a diet enriched in cholesterol and safflower oil without or with ezetimibe. The lipid-rich diet raised the absolute and relative cholesterol levels in bile more than fourfold. This increase was largely prevented by ezetimibe. These data are consistent with the recent finding that ezetimibe treatment significantly reduced biliary cholesterol saturation in patients with gallstones. PMID:18718997

  5. Reliable inverter systems

    NASA Technical Reports Server (NTRS)

    Nagano, S.

    1979-01-01

    Base driver with common-load-current feedback protects paralleled inverter systems from open or short circuits. Circuit eliminates total system oscillation that can occur in conventional inverters because of open circuit in primary transformer winding. Common feedback signal produced by functioning modules forces operating frequency of failed module to coincide with clock drive so module resumes normal operating frequency in spite of open circuit.

  6. Adenovirus RIDα uncovers a novel pathway requiring ORP1L for lipid droplet formation independent of NPC1

    PubMed Central

    Cianciola, Nicholas L.; Greene, Diane J.; Morton, Richard E.; Carlin, Cathleen R.

    2013-01-01

    Niemann–Pick disease type C (NPC) is caused by mutations in NPC1 or NPC2, which coordinate egress of low-density-lipoprotein (LDL)-cholesterol from late endosomes. We previously reported that the adenovirus-encoded protein RIDα rescues the cholesterol storage phenotype in NPC1-mutant fibroblasts. We show here that RIDα reconstitutes deficient endosome-to-endoplasmic reticulum (ER) transport, allowing excess LDL-cholesterol to be esterified by acyl-CoA:cholesterol acyltransferase and stored in lipid droplets (LDs) in NPC1-deficient cells. Furthermore, the RIDα pathway is regulated by the oxysterol-binding protein ORP1L. Studies have classified ORP1L as a sterol sensor involved in LE positioning downstream of GTP-Rab7. Our data, however, suggest that ORP1L may play a role in transport of LDL-cholesterol to a specific ER pool designated for LD formation. In contrast to NPC1, which is dispensable, the RIDα/ORP1L-dependent route requires functional NPC2. Although NPC1/NPC2 constitutes the major pathway, therapies that amplify minor egress routes for LDL-cholesterol could significantly improve clinical management of patients with loss-of-function NPC1 mutations. The molecular identity of putative alternative pathways, however, is poorly characterized. We propose RIDα as a model system for understanding physiological egress routes that use ORP1L to activate ER feedback responses involved in LD formation. PMID:24025716

  7. Characterisation of two deletions involving NPC1 and flanking genes in Niemann-Pick type C disease patients.

    PubMed

    Rodríguez-Pascau, Laura; Toma, Claudio; Macías-Vidal, Judit; Cozar, Mónica; Cormand, Bru; Lykopoulou, Lilia; Coll, Maria Josep; Grinberg, Daniel; Vilageliu, Lluïsa

    2012-12-01

    Niemann-Pick type C (NPC) disease is an autosomal recessive lysosomal disorder characterised by the accumulation of a complex pattern of lipids in the lysosomal-late endosomal system. More than 300 disease-causing mutations have been identified so far in the NPC1 and NPC2 genes, including indel, missense, nonsense and splicing mutations. Only one genomic deletion, of more than 23 kb, has been previously reported. We describe two larger structural variants, encompassing NPC1 and flanking genes, as a cause of the disease. QMPSF, SNP inheritance and CytoScan® HD Array were used to confirm and further characterise the presence of hemizygous deletions in two patients. One of the patients (NPC-57) bore a previously described missense mutation (p.T1066N) and an inherited deletion that included NPC1, C18orf8 and part of ANKRD29 gene. The second patient (NPC-G1) had a 1-bp deletion (c.852delT; p.F284Lfs*26) and a deletion encompassing the promoter region and exons 1-10 of NPC1 and the adjacent ANKRD29 and LAMA3. This study characterised two novel chromosomal microdeletions at 18q11-q12 that cause NPC disease and provide insight into missing NPC1 mutant alleles. PMID:23142039

  8. Novel multilevel inverter carrier-based PWM method

    SciTech Connect

    Tolbert, L.M.; Habetler, T.G.

    1999-10-01

    The advent of the transformerless multilevel inverter topology has brought forth various pulsewidth modulation (PWM) schemes as a means to control the switching of the active devices in each of the multiple voltage levels in the inverter. An analysis of how existing multilevel carrier-based PWM affects switch utilization for the different levels of a diode-clamped inverter is conducted. Two novel carrier-based multilevel PWM schemes are presented which help to optimize or balance the switch utilization in multilevel inverters. A 10-kW prototype six-level diode-clamped inverter has been built and controlled with the novel PWM strategies proposed in this paper to act as a voltage-source inverter for a motor drive.

  9. Filovirus receptor NPC1 contributes to species-specific patterns of ebolavirus susceptibility in bats

    PubMed Central

    Ng, Melinda; Ndungo, Esther; Kaczmarek, Maria E; Herbert, Andrew S; Binger, Tabea; Kuehne, Ana I; Jangra, Rohit K; Hawkins, John A; Gifford, Robert J; Biswas, Rohan; Demogines, Ann; James, Rebekah M; Yu, Meng; Brummelkamp, Thijn R; Drosten, Christian; Wang, Lin-Fa; Kuhn, Jens H; Müller, Marcel A; Dye, John M; Sawyer, Sara L; Chandran, Kartik

    2015-01-01

    Biological factors that influence the host range and spillover of Ebola virus (EBOV) and other filoviruses remain enigmatic. While filoviruses infect diverse mammalian cell lines, we report that cells from African straw-colored fruit bats (Eidolon helvum) are refractory to EBOV infection. This could be explained by a single amino acid change in the filovirus receptor, NPC1, which greatly reduces the affinity of EBOV-NPC1 interaction. We found signatures of positive selection in bat NPC1 concentrated at the virus-receptor interface, with the strongest signal at the same residue that controls EBOV infection in Eidolon helvum cells. Our work identifies NPC1 as a genetic determinant of filovirus susceptibility in bats, and suggests that some NPC1 variations reflect host adaptations to reduce filovirus replication and virulence. A single viral mutation afforded escape from receptor control, revealing a pathway for compensatory viral evolution and a potential avenue for expansion of filovirus host range in nature. DOI: http://dx.doi.org/10.7554/eLife.11785.001 PMID:26698106

  10. Photodynamic effects on nasopharyngeal carcinoma (NPC) cells with 5-aminolevulinic acid or its hexyl ester.

    PubMed

    Wu, R W K; Chu, E S M; Yow, C M N; Chen, J Y

    2006-10-01

    Nasopharyngeal carcinoma (NPC) is a prevalent cancer in Hong Kong and southern China. To explore a new modality of NPC treatment, 5-aminolevulinic acid (ALA) or its hexyl ester (ALA-H) mediated photodynamic therapy (PDT) was studied in vitro. The results show that NPC cells are sensitive to both ALA and ALA-H mediated PDT. However, ALA-H PDT is much more effective at cell inactivation than ALA-PDT, due to a higher efficiency of ALA-H on producing endogenous protoporphyrin (PpIX) in cells. Both apoptosis and necrosis are involved in cell death, but apoptosis plays a major role under the short time incubation of drugs. ALA and ALA-H mediated PDT not only destroy the cells directly, but also inhibit the expression of matrix metalloproteinase-2 (MMP2) in cells, a maker for tumor metastasis. The ALA-H shows promising PDT results on NPC in vitro; therefore it is worth investigating further in vivo for NPC treatment. PMID:16442708

  11. Ebola Virus and Severe Acute Respiratory Syndrome Coronavirus Display Late Cell Entry Kinetics: Evidence that Transport to NPC1+ Endolysosomes Is a Rate-Defining Step

    PubMed Central

    Mingo, Rebecca M.; Simmons, James A.; Shoemaker, Charles J.; Nelson, Elizabeth A.; Schornberg, Kathryn L.; D'Souza, Ryan S.; Casanova, James E.

    2014-01-01

    occurred in West Africa in 2014, and there was a significant outbreak of SARS in 2003. No effective vaccine or treatment has yet been approved for either virus. We present evidence that both viruses traffic late into the endocytic pathway, to NPC1+ LE/Lys, in order to enter host cells, and that they do so to access high levels of cathepsin activity, which both viruses use in their fusion-triggering mechanisms. This unexpected similarity suggests an unexplored vulnerability, trafficking to NPC1+ LE/Lys, as a therapeutic target for SARS and EBOV. PMID:25552710

  12. Resonant snubber inverter

    DOEpatents

    Lai, J.S.; Young, R.W. Sr.; Chen, D.; Scudiere, M.B.; Ott, G.W. Jr.; White, C.P.; McKeever, J.W.

    1997-06-24

    A resonant, snubber-based, soft switching, inverter circuit achieves lossless switching during dc-to-ac power conversion and power conditioning with minimum component count and size. Current is supplied to the resonant snubber branches solely by the main inverter switches. Component count and size are reduced by use of a single semiconductor switch in the resonant snubber branches. Component count is also reduced by maximizing the use of stray capacitances of the main switches as parallel resonant capacitors. Resonance charging and discharging of the parallel capacitances allows lossless, zero voltage switching. In one embodiment, circuit component size and count are minimized while achieving lossless, zero voltage switching within a three-phase inverter. 14 figs.

  13. Resonant snubber inverter

    DOEpatents

    Lai, Jih-Sheng; Young, Sr., Robert W.; Chen, Daoshen; Scudiere, Matthew B.; Ott, Jr., George W.; White, Clifford P.; McKeever, John W.

    1997-01-01

    A resonant, snubber-based, soft switching, inverter circuit achieves lossless switching during dc-to-ac power conversion and power conditioning with minimum component count and size. Current is supplied to the resonant snubber branches solely by the main inverter switches. Component count and size are reduced by use of a single semiconductor switch in the resonant snubber branches. Component count is also reduced by maximizing the use of stray capacitances of the main switches as parallel resonant capacitors. Resonance charging and discharging of the parallel capacitances allows lossless, zero voltage switching. In one embodiment, circuit component size and count are minimized while achieving lossless, zero voltage switching within a three-phase inverter.

  14. Multilevel cascade voltage source inverter with seperate DC sources

    DOEpatents

    Peng, Fang Zheng; Lai, Jih-Sheng

    2002-01-01

    A multilevel cascade voltage source inverter having separate DC sources is described herein. This inverter is applicable to high voltage, high power applications such as flexible AC transmission systems (FACTS) including static VAR generation (SVG), power line conditioning, series compensation, phase shifting and voltage balancing and fuel cell and photovoltaic utility interface systems. The M-level inverter consists of at least one phase wherein each phase has a plurality of full bridge inverters equipped with an independent DC source. This inverter develops a near sinusoidal approximation voltage waveform with only one switching per cycle as the number of levels, M, is increased. The inverter may have either single-phase or multi-phase embodiments connected in either wye or delta configurations.

  15. Multilevel cascade voltage source inverter with seperate DC sources

    DOEpatents

    Peng, Fang Zheng; Lai, Jih-Sheng

    1997-01-01

    A multilevel cascade voltage source inverter having separate DC sources is described herein. This inverter is applicable to high voltage, high power applications such as flexible AC transmission systems (FACTS) including static VAR generation (SVG), power line conditioning, series compensation, phase shifting and voltage balancing and fuel cell and photovoltaic utility interface systems. The M-level inverter consists of at least one phase wherein each phase has a plurality of full bridge inverters equipped with an independent DC source. This inverter develops a near sinusoidal approximation voltage waveform with only one switching per cycle as the number of levels, M, is increased. The inverter may have either single-phase or multi-phase embodiments connected in either wye or delta configurations.

  16. Multilevel cascade voltage source inverter with separate DC sources

    DOEpatents

    Peng, F.Z.; Lai, J.S.

    1997-06-24

    A multilevel cascade voltage source inverter having separate DC sources is described herein. This inverter is applicable to high voltage, high power applications such as flexible AC transmission systems (FACTS) including static VAR generation (SVG), power line conditioning, series compensation, phase shifting and voltage balancing and fuel cell and photovoltaic utility interface systems. The M-level inverter consists of at least one phase wherein each phase has a plurality of full bridge inverters equipped with an independent DC source. This inverter develops a near sinusoidal approximation voltage waveform with only one switching per cycle as the number of levels, M, is increased. The inverter may have either single-phase or multi-phase embodiments connected in either wye or delta configurations. 15 figs.

  17. Multilevel cascade voltage source inverter with seperate DC sources

    DOEpatents

    Peng, Fang Zheng; Lai, Jih-Sheng

    2001-04-03

    A multilevel cascade voltage source inverter having separate DC sources is described herein. This inverter is applicable to high voltage, high power applications such as flexible AC transmission systems (FACTS) including static VAR generation (SVG), power line conditioning, series compensation, phase shifting and voltage balancing and fuel cell and photovoltaic utility interface systems. The M-level inverter consists of at least one phase wherein each phase has a plurality of full bridge inverters equipped with an independent DC source. This inverter develops a near sinusoidal approximation voltage waveform with only one switching per cycle as the number of levels, M, is increased. The inverter may have either single-phase or multi-phase embodiments connected in either wye or delta configurations.

  18. Structural Insights into the Niemann-Pick C1 (NPC1)-Mediated Cholesterol Transfer and Ebola Infection.

    PubMed

    Gong, Xin; Qian, Hongwu; Zhou, Xinhui; Wu, Jianping; Wan, Tao; Cao, Pingping; Huang, Weiyun; Zhao, Xin; Wang, Xudong; Wang, Peiyi; Shi, Yi; Gao, George F; Zhou, Qiang; Yan, Nieng

    2016-06-01

    Niemann-Pick disease type C (NPC) is associated with mutations in NPC1 and NPC2, whose gene products are key players in the endosomal/lysosomal egress of low-density lipoprotein-derived cholesterol. NPC1 is also the intracellular receptor for Ebola virus (EBOV). Here, we present a 4.4 Å structure of full-length human NPC1 and a low-resolution reconstruction of NPC1 in complex with the cleaved glycoprotein (GPcl) of EBOV, both determined by single-particle electron cryomicroscopy. NPC1 contains 13 transmembrane segments (TMs) and three distinct lumenal domains A (also designated NTD), C, and I. TMs 2-13 exhibit a typical resistance-nodulation-cell division fold, among which TMs 3-7 constitute the sterol-sensing domain conserved in several proteins involved in cholesterol metabolism and signaling. A trimeric EBOV-GPcl binds to one NPC1 monomer through the domain C. Our structural and biochemical characterizations provide an important framework for mechanistic understanding of NPC1-mediated intracellular cholesterol trafficking and Ebola virus infection. PMID:27238017

  19. All-trans retinoic acid triggered antimicrobial activity against Mycobacterium tuberculosis is dependent on NPC2

    PubMed Central

    Inkeles, Megan S.; De Leon, Avelino; Pellegrini, Matteo; Krutzik, Stephan R.; Liu, Philip T.

    2014-01-01

    A role for vitamin A in host defense against Mycobacterium tuberculosis has been suggested through epidemiological and in vitro studies; however, the mechanism is unclear. Here, we demonstrate that vitamin A-triggered antimicrobial activity against M. tuberculosis requires expression of Niemann-Pick disease type C2 (NPC2). Comparison of monocytes stimulated with all-trans retinoic acid (ATRA) or 1,25-dihydroxyvitamin D3 (1,25D3), the biologically active forms of vitamin A and vitamin D, respectively, indicates that ATRA and 1,25D3 induce mechanistically distinct antimicrobial activities. Stimulation of primary human monocytes with ATRA did not result in expression of the antimicrobial peptide cathelicidin, which is required for 1,25D3 antimicrobial activity. In contrast, ATRA triggers a reduction in the total cellular cholesterol concentration, whereas 1,25D3 did not. Blocking ATRA-induced cellular cholesterol reduction inhibits antimicrobial activity as well. Bioinformatic analysis of ATRA and 1,25D3 induced gene profiles suggests Niemann-Pick disease type C2 (NPC2) is a key gene in ATRA-induced cholesterol regulation. Knockdown experiments demonstrate that ATRA-mediated decrease of total cellular cholesterol content and increase in lysosomal acidification are both dependent upon expression of NPC2. Expression of NPC2 was lower in caseous tuberculosis granulomas and M. tuberculosis-infected monocytes compared to normal lung and uninfected cells, respectively. Loss of NPC2 expression ablated ATRA-induced antimicrobial activity. Taken together, these results suggest that the vitamin A-mediated antimicrobial mechanism against M. tuberculosis requires NPC2-dependent expression and function, indicating a key role for cellular cholesterol regulation in the innate immune response. PMID:24501203

  20. Energy-Saving Inverter

    NASA Technical Reports Server (NTRS)

    Rippel, W. E.; Edwards, D. B.

    1984-01-01

    Commutation by field-effect transistor allows more efficient operation. High voltage field-effect transistor (FET) controls silicon controlled rectifiers (SCR's). Circuit requires only one capacitor and one inductor in commutation circuit: simpler, more efficient, and more economical than conventional inverters. Adaptable to dc-to-dc converters.

  1. Inverting the Achievement Pyramid

    ERIC Educational Resources Information Center

    White-Hood, Marian; Shindel, Melissa

    2006-01-01

    Attempting to invert the pyramid to improve student achievement and increase all students' chances for success is not a new endeavor. For decades, educators have strategized, formed think tanks, and developed school improvement teams to find better ways to improve the achievement of all students. Currently, the No Child Left Behind Act (NCLB) is…

  2. Program Predicts Nonlinear Inverter Performance

    NASA Technical Reports Server (NTRS)

    Al-Ayoubi, R. R.; Oepomo, T. S.

    1985-01-01

    Program developed for ac power distribution system on Shuttle orbiter predicts total load on inverters and node voltages at each of line replaceable units (LRU's). Mathematical model simulates inverter performance at each change of state in power distribution system.

  3. Structural Basis of Sterol Binding by NPC2, a Lysosomal Protein Deficient in Niemann-Pick Type C2 Disease

    SciTech Connect

    Xu,S.; Benoff, B.; Liou, H.; Lobel, P.; Stock, A.

    2007-01-01

    NPC2 is a small lysosomal glycoprotein that binds cholesterol with submicromolar affinity. Deficiency in NPC2 is the cause of Niemann-Pick type C2 disease, a fatal neurovisceral disorder characterized by accumulation of cholesterol in lysosomes. Here we report the crystal structure of bovine NPC2 bound to cholesterol-3-O-sulfate, an analog that binds with greater apparent affinity than cholesterol. Structures of both apo-bound and sterol-bound NPC2 were observed within the same crystal lattice, with an asymmetric unit containing one molecule of apoNPC2 and two molecules of sterol-bound NPC2. As predicted from a previously determined structure of apoNPC2, the sterol binds in a deep hydrophobic pocket sandwiched between the two {beta}-sheets of NPC2, with only the sulfate substituent of the ligand exposed to solvent. In the two available structures of apoNPC2, the incipient ligand-binding pocket, which ranges from a loosely packed hydrophobic core to a small tunnel, is too small to accommodate cholesterol. In the presence of sterol, the pocket expands, facilitated by a slight separation of the {beta}-strands and substantial reorientation of some side chains, resulting in a perfect molding of the pocket around the hydrocarbon portion of cholesterol. A notable feature is the repositioning of two aromatic residues at the tunnel entrance that are essential for NPC2 function. The NPC2 structures provide evidence of a malleable binding site, consistent with the previously documented broad range of sterol ligand specificity.

  4. Loss of NPC1 function in a patient with a co-inherited novel insulin receptor mutation does not grossly modify the severity of the associated insulin resistance.

    PubMed

    Kirk, J; Porter, K M; Parker, V; Barroso, I; O'Rahilly, S; Hendriksz, C; Semple, R K

    2010-12-01

    In Npc1 null mice, a model for Niemann Pick Disease Type C1, it has been reported that hepatocyte insulin receptor function is significantly impaired, consistent with growing evidence that membrane fluidity and microdomain structure have an important role in insulin signal transduction. However, whether insulin receptor function is also compromised in human Niemann Pick disease Type C1 is unclear. We now report a girl who developed progressive dementia, ataxia and opthalmoplegia from 9 years old, followed by severe acanthosis nigricans, hirsutism and acne at 11 years old. She was diagnosed with Niemann Pick Disease type C1 (OMIM#257220) based on positive filipin staining and reduced cholesterol-esterifying activity in dermal fibroblasts, and homozygosity for the p.Ile1061Thr NPC1 mutation. Further analysis revealed her also to be heterozygous for a novel trinucleotide deletion (c.3659 + 1_3659 + 3delGTG) at the end of exon 20 of INSR, encoding the insulin receptor, leading to deletion of Trp1193 in the intracellular tyrosine kinase domain. INSR mRNA and protein levels were normal in dermal fibroblasts, consistent with a primary signal transduction defect in the mutant receptor. Although the proband was significantly more insulin resistant than her father, who carried the INSR mutation but was only heterozygous for the NPC1 variant, their respective degrees of IR were very similar to those previously reported in a father-daughter pair with the closely related p.Trp1193Leu INSR mutation. This suggests that loss of NPC1 function, with attendant changes in membrane cholesterol composition, does not significantly modify the IR phenotype, even in the context of severely impaired INSR function. PMID:20521171

  5. An inverter/controller subsystem optimized for photovoltaic applications

    NASA Technical Reports Server (NTRS)

    Pickrell, R. L.; Osullivan, G.; Merrill, W. C.

    1978-01-01

    Conversion of solar array dc power to ac power stimulated the specification, design, and simulation testing of an inverter/controller subsystem tailored to the photovoltaic power source characteristics. Optimization of the inverter/controller design is discussed as part of an overall photovoltaic power system designed for maximum energy extraction from the solar array. The special design requirements for the inverter/ controller include: a power system controller (PSC) to control continuously the solar array operating point at the maximum power level based on variable solar insolation and cell temperatures; and an inverter designed for high efficiency at rated load and low losses at light loadings to conserve energy.

  6. HNF1α and SREBP2 are important regulators of NPC1L1 in human liver

    PubMed Central

    Pramfalk, Camilla; Jiang, Zhao-Yan; Cai, Qu; Hu, Hai; Zhang, Sheng-Dao; Han, Tian-Quan; Eriksson, Mats; Parini, Paolo

    2010-01-01

    Niemann-Pick C1-like 1 (NPC1L1), a key regulator of intestinal cholesterol absorption, is highly expressed in human liver. Here, we aimed to gain more insight into mechanisms participating in its hepatic regulation in humans. Correlation analysis in livers from Chinese patients with and without gallstone disease revealed strong positive correlations between NPC1L1 and sterol regulatory element binding protein 2 (SREBP2) (r = 0.74, P < 0.05) and between NPC1L1 and hepatic nuclear factor α (HNF4α) (r = 0.53, P < 0.05) mRNA expression. HNF4α is an upstream regulator of HNF1α; thus, we also tested whether HNF1α participates in the regulation of NPC1L1. We showed a dose-dependent regulation by SREBP2 on the NPC1L1 promoter activity and mRNA expression in HuH7 cells. Chromatin immunoprecipitation assay confirmed the binding of SREBP2 to the promoter in vivo. Surprisingly, HNF4α slightly decreased the NPC1L1 promoter activity but had no effect on its gene expression. By contrast, HNF1α increased the promoter activity and the gene expression, and an important HNF1 binding site was identified within the human NPC1L1 promoter. ChIP assays confirmed that HNF1α can bind to the NPC1L1 promoter in vivo. PMID:20460578

  7. Cholesterol accumulation in Niemann Pick type C (NPC) model cells causes a shift in APP localization to lipid rafts

    SciTech Connect

    Kosicek, Marko; Malnar, Martina; Goate, Alison; Hecimovic, Silva

    2010-03-12

    It has been suggested that cholesterol may modulate amyloid-{beta} (A{beta}) formation, a causative factor of Alzheimer's disease (AD), by regulating distribution of the three key proteins in the pathogenesis of AD ({beta}-amyloid precursor protein (APP), {beta}-secretase (BACE1) and/or presenilin 1 (PS1)) within lipid rafts. In this work we tested whether cholesterol accumulation upon NPC1 dysfunction, which causes Niemann Pick type C disease (NPC), causes increased partitioning of APP into lipid rafts leading to increased CTF/A{beta} formation in these cholesterol-rich membrane microdomains. To test this we used CHO NPC1{sup -/-} cells (NPC cells) and parental CHOwt cells. By sucrose density gradient centrifugation we observed a shift in fl-APP/CTF compartmentalization into lipid raft fractions upon cholesterol accumulation in NPC vs. wt cells. Furthermore, {gamma}-secretase inhibitor treatment significantly increased fl-APP/CTF distribution in raft fractions in NPC vs. wt cells, suggesting that upon cholesterol accumulation in NPC1-null cells increased formation of APP-CTF and its increased processing towards A{beta} occurs in lipid rafts. Our results support that cholesterol overload, such as in NPC disease, leads to increased partitioning of APP/CTF into lipid rafts resulting in increased amyloidogenic processing of APP in these cholesterol-rich membranes. This work adds to the mechanism of the cholesterol-effect on APP processing and the pathogenesis of Alzheimer's disease and supports the role of lipid rafts in these processes.

  8. Acid sphingomyelinase activity is regulated by membrane lipids and facilitates cholesterol transfer by NPC2[S

    PubMed Central

    Oninla, Vincent O.; Breiden, Bernadette; Babalola, Jonathan O.; Sandhoff, Konrad

    2014-01-01

    During endocytosis, membrane components move to intraluminal vesicles of the endolysosomal compartment for digestion. At the late endosomes, cholesterol is sorted out mainly by two sterol-binding proteins, Niemann-Pick protein type C (NPC)1 and NPC2. To study the NPC2-mediated intervesicular cholesterol transfer, we developed a liposomal assay system. (Abdul-Hammed, M., B. Breiden, M. A. Adebayo, J. O. Babalola, G. Schwarzmann, and K. Sandhoff. 2010. Role of endosomal membrane lipids and NPC2 in cholesterol transfer and membrane fusion. J. Lipid Res. 51: 1747–1760.) Anionic lipids stimulate cholesterol transfer between liposomes while SM inhibits it, even in the presence of anionic bis(monoacylglycero)phosphate (BMP). Preincubation of vesicles containing SM with acid sphingomyelinase (ASM) (SM phosphodiesterase, EC 3.1.4.12) results in hydrolysis of SM to ceramide (Cer), which enhances cholesterol transfer. Besides SM, ASM also cleaves liposomal phosphatidylcholine. Anionic phospholipids derived from the plasma membrane (phosphatidylglycerol and phosphatidic acid) stimulate SM and phosphatidylcholine hydrolysis by ASM more effectively than BMP, which is generated during endocytosis. ASM-mediated hydrolysis of liposomal SM was also stimulated by incorporation of diacylglycerol (DAG), Cer, and free fatty acids into the liposomal membranes. Conversely, phosphatidylcholine hydrolysis was inhibited by incorporation of cholesterol, Cer, DAG, monoacylglycerol, and fatty acids. Our data suggest that SM degradation by ASM is required for physiological secretion of cholesterol from the late endosomal compartment, and is a key regulator of endolysosomal lipid digestion. PMID:25339683

  9. National Renewable Energy Laboratory Pyrheliometer Comparisons: 24 September - 5 October 2012 (NPC-2012)

    SciTech Connect

    Stoffel, T.; Reda, I.

    2013-05-01

    The NREL Pyrheliometer Comparisons for 2012 (NPC-2012) were held at the Solar Radiation Research Laboratory in Golden, Colorado, from September 24 through October 5 for the purpose of transferring the World Radiometric Reference (WRR) to participating instrument. Twenty scientists and engineers operated 32 absolute cavity radiometers and 18 conventional thermopile-based pyrheliometers to simultaneously measure clear-sky direct normal irradiance during the comparisons. The transfer standard group of reference radiometers for NPC-2012 consisted of four NREL radiometers with direct traceability to the WRR, having participated in the Eleventh International Pyrheliometer Comparisons (IPC-XI) hosted by the World Radiation Center in the fall of 2010. As the result of NPC-2012, each participating absolute cavity radiometer was assigned a new WRR transfer factor, computed as the reference irradiance computed by the transfer standard group divided by the observed irradiance from the participating radiometer. The performance of the transfer standard group during NPC-2012 was consistent with previous comparisons, including IPC-XI. The measurement performance of the transfer standard group allowed the transfer of the WRR to each participating radiometer with an estimated uncertainty of +/- 0.33% with respect to the International System of Units.

  10. Inverter ratio failure detector

    NASA Technical Reports Server (NTRS)

    Wagner, A. P.; Ebersole, T. J.; Andrews, R. E. (Inventor)

    1974-01-01

    A failure detector which detects the failure of a dc to ac inverter is disclosed. The inverter under failureless conditions is characterized by a known linear relationship of its input and output voltages and by a known linear relationship of its input and output currents. The detector includes circuitry which is responsive to the detector's input and output voltages and which provides a failure-indicating signal only when the monitored output voltage is less by a selected factor, than the expected output voltage for the monitored input voltage, based on the known voltages' relationship. Similarly, the detector includes circuitry which is responsive to the input and output currents and provides a failure-indicating signal only when the input current exceeds by a selected factor the expected input current for the monitored output current based on the known currents' relationship.

  11. Inverted organic photovoltaic cells.

    PubMed

    Wang, Kai; Liu, Chang; Meng, Tianyu; Yi, Chao; Gong, Xiong

    2016-05-21

    The advance in lifestyle, modern industrialization and future technological revolution are always at high expense of energy consumption. Unfortunately, there exist serious issues such as limited storage, high cost and toxic contamination in conventional fossil fuel energy sources. Instead, solar energy represents a renewable, economic and green alternative in the future energy market. Among the photovoltaic technologies, organic photovoltaics (OPVs) demonstrate a cheap, flexible, clean and easy-processing way to convert solar energy into electricity. However, OPVs with a conventional device structure are still far away from industrialization mainly because of their short lifetime and the energy-intensive deposition of top metal electrode. To address the stability and cost issue simultaneously, an inverted device structure has been introduced into OPVs, bridging laboratory research with practical application. In this review, recent progress in device structures, working mechanisms, functions and advances of each component layer as well their correlations with the efficiency and stability of inverted OPVs are reviewed and illustrated. PMID:27087582

  12. Inverted organic photosensitive device

    SciTech Connect

    Forrest, Stephen R.; Tong, Xiaoran; Lee, Jun Yeob; Cho, Yong Joo

    2015-09-08

    There is disclosed a method for preparing the surface of a metal substrate. The present disclosure also relates to an organic photovoltaic device including a metal substrate made by such method. Also disclosed herein is an inverted photosensitive device including a stainless steel foil reflective electrode, an organic donor-acceptor heterojunction over the reflective electrode, and a transparent electrode over the donor-acceptor heterojunction.

  13. Sterol transfer between cyclodextrin and membranes: similar but not identical mechanism to NPC2-mediated cholesterol transfer.

    PubMed

    McCauliff, Leslie A; Xu, Zhi; Storch, Judith

    2011-08-30

    Niemann--Pick C disease is an inherited disorder in which cholesterol and other lipids accumulate in the late endosomal/lysosomal compartment. Recently, cyclodextrins (CD) have been shown to reduce symptoms and extend lifespan in animal models of the disease. In the present studies we examined the mechanism of sterol transport by CD using in vitro model systems and fluorescence spectroscopy and NPC2-deficient fibroblasts. We demonstrate that cholesterol transport from the lysosomal cholesterol-binding protein NPC2 to CD occurs via aqueous diffusional transfer and is very slow; the rate-limiting step appears to be dissociation of cholesterol from NPC2, suggesting that specific interactions between NPC2 and CD do not occur. In contrast, the transfer rate of the fluorescent cholesterol analogue dehydroergosterol (DHE) from CD to phospholipid membranes is very rapid and is directly proportional to the acceptor membrane concentration, as is DHE transfer from membranes to CD. Moreover, CD dramatically increases the rate of sterol transfer between membranes, with rates that can approach those mediated by NPC2. The results suggest that sterol transfer from CD to membranes occurs by a collisional transfer mechanism involving direct interaction of CD with membranes, similar to that shown previously for NPC2. For CD, however, absolute rates are slower compared to NPC2 for a given concentration, and the lysosomal phospholipid lysobisphosphatidic acid (LBPA) does not stimulate rates of sterol transfer between membranes and CD. As expected from the apparent absence of interaction between CD and NPC2, the addition of CD to NPC2-deficient fibroblasts rapidly rescued the cholesterol accumulation phenotype. Thus, the recent observations of CD efficacy in mouse models of NPC disease are likely the result of CD enhancement of cholesterol transport between membranes, with rapid sterol transfer occurring during CD--membrane interactions. PMID:21740003

  14. Antinociceptive profile of the pseudopeptide B2 bradykinin receptor antagonist NPC 18688 in mice.

    PubMed Central

    Corrêa, C. R.; Kyle, D. J.; Chakraverty, S.; Calixto, J. B.

    1996-01-01

    1. The purpose of this study was to investigate the topical and systemic anti-hyperalgesic effect of the newly-developed pseudopeptide B2 receptor antagonist, NPC 18688, in different models of nociception in mice. 2. Given systemically 30 min beforehand, NPC 18688 (10-300 nmol kg-1, i.p.) caused no agonist effect, but produced a dose-related and significant inhibition of abdominal constrictions caused by intraperitoneal injection of acetic acid (0.6%), acetylcholine (ACh, 4.5 mg kg-1) or kaolin (50 mg kg-1). The calculated mean ID50s and the percentages of maximal inhibitions (MI) for these effects were: 77, 34 and > 300 nmol kg-1 and 65 +/- 6, 70 +/- 5 and 40 +/- 3%, respectively. The anti-hyperalgesic effect of NPC 18688 (100 nmol kg-1, i.p.) occurred rapidly (30 min) and lasted for at least 150 min. Hoe 140 (3-30 nmol kg-1, i.p.) given 30 min beforehand also inhibited, in a graded manner, acetic acid and ACh-induced writhing, with mean ID50s and MI of 6 and 9 nmol kg-1 and 56 +/- 7 and 62 +/- 6%, respectively. 3. NPC 18688 (10-300 nmol kg-1, i.p.) caused a graded inhibition of both phases of formalin (2.5%)-induced pain, its effects being more potent in relation to the second phase of the formalin test. The calculated mean ID50s and the MI were > 300 and 60 nmol kg-1 and 20 +/- 3 and 60 +/- 5% against the first and second phases of formalin-induced nociception, respectively. NPC 18688 at the same doses also inhibited, in a dose-related manner, formalin-induced paw oedema (MI of 35 +/- 3%). 4. When injected locally in the mouse paw, NPC 18688 (2, 10 and 20 nmol/paw) had no agonist activity. However, when co-injected with formalin NPC 18688 (2-20 nmol/paw), it produced significant inhibition of both phases of formalin response, with MI of 40 +/- 3 and 33 +/- 2%, respectively. NPC 18688 at 10 nmol/paw also significantly inhibited formalin-induced paw oedema (25 +/- 2%). 5. Given intraperitoneally, NPC 18688 (30-300 nmol kg-1) determined a graded inhibition of the

  15. Integral inverter/battery charger for use in electric vehicles

    NASA Technical Reports Server (NTRS)

    Thimmesch, D.

    1983-01-01

    The design and test results of a thyristor based inverter/charger are discussed. A battery charger is included integral to the inverter by using a subset of the inverter power circuit components. The resulting charger provides electrical isolation between the vehicle propulsion battery and ac line and is capable of charging a 25 kWh propulsion battery in 8 hours from a 220 volt ac line. The integral charger employs the inverter commutation components at a resonant ac/dc isolated converter rated at 3.6 kW. Charger efficiency and power factor at an output power of 3.6 kW are 86% and 95% respectively. The inverter, when operated with a matching polyphase ac induction motor and nominal 132 volt propulsion battery, can provide a peak shaft power of 34 kW (45 ph) during motoring operation and 45 kW (60 hp) during regeneration. Thyristors are employed for the inverter power switching devices and are arranged in an input-commutated topology. This configuration requires only two thyristors to commutate the six main inverter thyristors. Inverter efficiency during motoring operation at motor shaft speeds above 450 rad/sec (4300 rpm) is 92-94% for output power levels above 11 KW (15 hp). The combined ac inverter/charger package weighs 47 kg (103 lbs).

  16. The implementation in-house dose verification for IMRT and VMAT on breast cancer and NPC cases

    NASA Astrophysics Data System (ADS)

    Azzi, A.; Dimitri, F. Y.; Pawiro, S. A.

    2016-03-01

    IMRT and VMAT have been widely implemented on breast cancer and NPC cases. Dose verification was conducted to ensure the comparison between dose delivered and prescribe dose in TPS to obtain optimal results and the dose delivered. The gafchromic films measurement was done for breast and NPC simulation on RANDO Phantom, irradiating film by 6 MV photon with 200 cGy and scanned with EPSON V700 using 72 dpi. Dose distribution was calculated using the MATLAB-based in-house algorithm. In order to evaluate the gamma index, gafchromic films and MatriXX 2D array were placed in the Multi Cube and irradiated with EPID in same position. Dose distribution differences for IMRT and VMAT with modalities to TPS on film was 5.34% and 6.68% for NPC PTV70; 12.81% and 6.15% for NPC PTV50; 11.14% and 10.80% for breast cancer. Gamma index differences on IMRT with modalities to MatriXX 2D array and EPID was -0.09% and 5.13% for NPC; 0.51% and 2.28% for breast cancer. On the other hand, gamma index difference on VMAT was -1.65% and 1.43% for NPC; 0.19% and 4.38% for breast cancer. This measurement method can be used to verify dose for breast cancer and NPC cases in IMRT and VMAT.

  17. A multilevel voltage-source inverter with separate dc sources for static var generation

    SciTech Connect

    Peng, Fang Zheng |; Lai, Jih-Sheng; McKeever, J.; VanCoevering, J.

    1995-09-01

    A new multilevel voltage-source inverter with a separate dc sources is proposed for high-voltage, high-power applications, such as flexible ac transmission systems (FACTS) including static var generation (SVG), power line conditioning, series compensation, phase shifting, voltage balancing, fuel cell and photovoltaic utility systems interfacing, etc. The new M-level inverter consists of (M-1)/2 single phase full bridges in which each bridge has its own separate dc source. This inverter can generate almost sinusoidal waveform voltage with only one time switching per cycle as the number of levels increases. It can solve the problems of conventional transformer-based multipulse inverters and the problems of the multilevel diode-clamped inverter and the multilevel flying capacitor inverter. To demonstrate the superiority of the new inverter, a SVG system using the new inverter topology is discussed through analysis, simulation and experiment.

  18. Inverted glass harp

    NASA Astrophysics Data System (ADS)

    Quinn, Daniel B.; Rosenberg, Brian J.

    2015-08-01

    We present an analytical treatment of the acoustics of liquid-filled wine glasses, or "glass harps." The solution is generalized such that under certain assumptions it reduces to previous glass harp models, but also leads to a proposed musical instrument, the "inverted glass harp," in which an empty glass is submerged in a liquid-filled basin. The versatility of the solution demonstrates that all glass harps are governed by a family of solutions to Laplace's equation around a vibrating disk. Tonal analyses of recordings for a sample glass are offered as confirmation of the scaling predictions.

  19. Inverted glass harp.

    PubMed

    Quinn, Daniel B; Rosenberg, Brian J

    2015-08-01

    We present an analytical treatment of the acoustics of liquid-filled wine glasses, or "glass harps." The solution is generalized such that under certain assumptions it reduces to previous glass harp models, but also leads to a proposed musical instrument, the "inverted glass harp," in which an empty glass is submerged in a liquid-filled basin. The versatility of the solution demonstrates that all glass harps are governed by a family of solutions to Laplace's equation around a vibrating disk. Tonal analyses of recordings for a sample glass are offered as confirmation of the scaling predictions. PMID:26382336

  20. Gas cooled traction drive inverter

    SciTech Connect

    Chinthavali, Madhu Sudhan

    2013-10-08

    The present invention provides a modular circuit card configuration for distributing heat among a plurality of circuit cards. Each circuit card includes a housing adapted to dissipate heat in response to gas flow over the housing. In one aspect, a gas-cooled inverter includes a plurality of inverter circuit cards, and a plurality of circuit card housings, each of which encloses one of the plurality of inverter cards.

  1. Gas cooled traction drive inverter

    DOEpatents

    Chinthavali, Madhu Sudhan

    2016-04-19

    The present invention provides a modular circuit card configuration for distributing heat among a plurality of circuit cards. Each circuit card includes a housing adapted to dissipate heat in response to gas flow over the housing. In one aspect, a gas-cooled inverter includes a plurality of inverter circuit cards, and a plurality of circuit card housings, each of which encloses one of the plurality of inverter cards.

  2. Inverter Modeling For Accurate Energy Predictions Of Tracking HCPV Installations

    NASA Astrophysics Data System (ADS)

    Bowman, J.; Jensen, S.; McDonald, Mark

    2010-10-01

    High efficiency high concentration photovoltaic (HCPV) solar plants of megawatt scale are now operational, and opportunities for expanded adoption are plentiful. However, effective bidding for sites requires reliable prediction of energy production. HCPV module nameplate power is rated for specific test conditions; however, instantaneous HCPV power varies due to site specific irradiance and operating temperature, and is degraded by soiling, protective stowing, shading, and electrical connectivity. These factors interact with the selection of equipment typically supplied by third parties, e.g., wire gauge and inverters. We describe a time sequence model accurately accounting for these effects that predicts annual energy production, with specific reference to the impact of the inverter on energy output and interactions between system-level design decisions and the inverter. We will also show two examples, based on an actual field design, of inverter efficiency calculations and the interaction between string arrangements and inverter selection.

  3. Alternative algebras admitting derivations with invertible values and invertible derivations

    NASA Astrophysics Data System (ADS)

    Kaygorodov, I. B.; Popov, Yu S.

    2014-10-01

    We prove an analogue of the Bergen-Herstein-Lanski theorem for alternative algebras: describe all alternative algebras that admit derivations with invertible values. We also prove an analogue of Moens' theorem for alternative algebras (a finite-dimensional alternative algebra over a field of characteristic zero is nilpotent if and only if it admits an invertible Leibniz derivation).

  4. Miglustat Reverts the Impairment of Synaptic Plasticity in a Mouse Model of NPC Disease

    PubMed Central

    D'Arcangelo, G.; Grossi, D.; Racaniello, M.; Cardinale, A.; Zaratti, A.; Rufini, S.; Cutarelli, A.; Tancredi, V.; Merlo, D.; Frank, C.

    2016-01-01

    Niemann-Pick type C disease is an autosomal recessive storage disorder, characterized by abnormal sequestration of unesterified cholesterol within the late endolysosomal compartment of cells and accumulation of gangliosides and other sphingolipids. Progressive neurological deterioration and insurgence of symptoms like ataxia, seizure, and cognitive decline until severe dementia are pathognomonic features of the disease. Here, we studied synaptic plasticity phenomena and evaluated ERKs activation in the hippocampus of BALB/c NPC1−/− mice, a well described animal model of the disease. Our results demonstrated an impairment of both induction and maintenance of long term synaptic potentiation in NPC1−/− mouse slices, associated with the lack of ERKs phosphorylation. We then investigated the effects of Miglustat, a recent approved drug for the treatment of NPCD. We found that in vivo Miglustat administration in NPC1−/− mice was able to rescue synaptic plasticity deficits, to restore ERKs activation and to counteract hyperexcitability. Overall, these data indicate that Miglustat may be effective for treating the neurological deficits associated with NPCD, such as seizures and dementia. PMID:26885401

  5. Niemann-Pick C1-Like 1 (NPC1L1) Protein in Intestinal and Hepatic Cholesterol Transport

    PubMed Central

    Jia, Lin; Betters, Jenna L.; Yu, Liqing

    2014-01-01

    Increased blood cholesterol is an independent risk factor for atherosclerotic cardiovascular disease. Cholesterol homeostasis in the body is controlled mainly by endogenous synthesis, intestinal absorption, and hepatic excretion. Niemann-Pick C1-Like 1 (NPC1L1) is a polytopic transmembrane protein localized at the apical membrane of enterocytes and the canalicular membrane of hepatocytes. It functions as a sterol transporter to mediate intestinal cholesterol absorption and counterbalances hepatobiliary cholesterol excretion. NPC1L1 is the molecular target of ezetimibe, a potent cholesterol absorption inhibitor that is widely used in treating hypercholesterolemia. Recent findings suggest that NPC1L1 deficiency or ezetimibe treatment also prevents diet-induced hepatic steatosis and obesity in addition to reducing blood cholesterol. Future studies should focus on molecular mechanisms underlying NPC1L1-dependent cholesterol transport and elucidation of how a cholesterol transporter modulates the pathogenesis of metabolic diseases. PMID:20809793

  6. Dynamic performance and control of a static var generator using cascade multilevel inverters

    SciTech Connect

    Peng, Fang Zheng; Lai, Jih-Sheng

    1996-10-01

    A cascade multilevel inverter is proposed for static VAR shifting, compensation/generation applications. The new cascade M-level inverter consists of (M-1)/2 single-phase full bridges in which each bridge has its own separate dc source. This inverter can generate almost sinusoidal waveform voltage with only one time switching per cycle. It can eliminate the need for transformers in multipulse inverters. A prototype static VAR generator (SVG) system using 11- level cascade inverter (21-level line-to-line voltage waveform) has been built. The output voltage waveform is equivalent to that of a 60- pulse inverter. This paper focuses on dynamic performance of the cascade inverter based SVG system. Control schemes are proposed to achieve a fast response which is impossible for a conventional static VAR compensator (SVC). Analytical, simulated and experimental results show the superiority of the proposed SVG system.

  7. The NPC1L1 Polymorphism 1679C>G Is Associated with Gallstone Disease in Chinese Patients

    PubMed Central

    Fei, Jian; Zhang, Sheng-Dao; Han, Tian-Quan; Hu, Hai; Jiang, Zhao-Yan

    2016-01-01

    Niemann Pick Type C1 Like 1 (NPC1L1) protein plays a key role in intestinal and hepatic cholesterol metabolism in humans. Genetic variation in NPC1L1 has been widely studied in recent years. We analyzed NPC1L1 single nucleotide polymorphisms in Chinese gallstone disease patients to investigate their association with gallstone disease. NPC1L1 mRNA expression was also measured in liver biopsies from patients with cholesterol gallstone disease and compared between genotypes. The G allele of the g1679C>G (rs2072183) polymorphism was significantly more prevalent in patients with gallstones compared with gallstone-free subjects. Moreover, patients carrying the G allele had lower hepatic NPC1L1 mRNA expression and higher biliary cholesterol (molar percentages) and cholesterol saturation index. Our study suggests that the G allele of the NPC1L1 polymorphism g1679C>G may be a positive marker of gallstone formation risk. PMID:26800364

  8. The NPC1L1 Polymorphism 1679C>G Is Associated with Gallstone Disease in Chinese Patients.

    PubMed

    Wu, Jian; Cui, Wei; Cai, Qu; Fei, Jian; Zhang, Sheng-Dao; Han, Tian-Quan; Hu, Hai; Jiang, Zhao-Yan

    2016-01-01

    Niemann Pick Type C1 Like 1 (NPC1L1) protein plays a key role in intestinal and hepatic cholesterol metabolism in humans. Genetic variation in NPC1L1 has been widely studied in recent years. We analyzed NPC1L1 single nucleotide polymorphisms in Chinese gallstone disease patients to investigate their association with gallstone disease. NPC1L1 mRNA expression was also measured in liver biopsies from patients with cholesterol gallstone disease and compared between genotypes. The G allele of the g1679C>G (rs2072183) polymorphism was significantly more prevalent in patients with gallstones compared with gallstone-free subjects. Moreover, patients carrying the G allele had lower hepatic NPC1L1 mRNA expression and higher biliary cholesterol (molar percentages) and cholesterol saturation index. Our study suggests that the G allele of the NPC1L1 polymorphism g1679C>G may be a positive marker of gallstone formation risk. PMID:26800364

  9. Cholesterol homeostatic responses provide biomarkers for monitoring treatment for the neurodegenerative disease Niemann–Pick C1 (NPC1)

    PubMed Central

    Tortelli, Brett; Fujiwara, Hideji; Bagel, Jessica H.; Zhang, Jessie; Sidhu, Rohini; Jiang, Xuntian; Yanjanin, Nicole M.; Shankar, Roopa Kanakatti; Carillo-Carasco, Nuria; Heiss, John; Ottinger, Elizabeth; Porter, Forbes D.; Schaffer, Jean E.; Vite, Charles H.; Ory, Daniel S.

    2014-01-01

    Niemann–Pick C1 (NPC1) disease is a rare, neurodegenerative lysosomal cholesterol storage disorder, typified by progressive cognitive and motor function impairment. Affected individuals usually succumb to the disease in adolescence. 2-Hydroxypropyl-β-cyclodextrin (HP-β-CD) has emerged as a promising intervention that reduces lipid storage and prolongs survival in NPC1 disease animal models. A barrier to the development of HP-β-CD and other treatments for NPC disease has been the lack of validated biochemical measures to evaluate efficacy. Here we explored whether cholesterol homeostatic responses resulting from HP-β-CD-mediated redistribution of sequestered lysosomal cholesterol could provide biomarkers to monitor treatment. Upon direct CNS delivery of HP-β-CD, we found increases in plasma 24(S)-HC in two independent NPC1 disease animal models, findings that were confirmed in human NPC1 subjects receiving HP-β-CD. Since circulating 24(S)-HC is almost exclusively CNS-derived, the increase in plasma 24(S)-HC provides a peripheral, non-invasive measure of the CNS effect of HP-β-CD. Our findings suggest that plasma 24(S)-HC, along with the other cholesterol-derived markers examined in this study, can serve as biomarkers that will accelerate development of therapeutics for NPC1 disease. PMID:24964810

  10. Intelligent Control of an Inverted Pendulum

    NASA Astrophysics Data System (ADS)

    Rekdalsbakken, Webjorn

    An inverted pendulum represents an unstable system which is excellent for demonstrating the use of feedback control with different kinds of control strategies. In this work state feedback of the inverted pendulum is examined. First a pole placement algorithm is explored. After that artificial intelligence (AI) methods are investigated to better cope with the nonlinearities of the physical model. The technique used is based on a hybrid system combining a neural network (NN) with a genetic algorithm (GA). The NN controller is trained by the GA against the behaviour of the physical model. The results of the training process show that the chromosome population tends to station at a suboptimal level, and that changes in the environmental parameters have to take place to reach a new optimal level. By systematically changing these parameters the NN controller will gradually adapt to the pendulum behaviour.

  11. Coaxial inverted geometry transistor having buried emitter

    NASA Technical Reports Server (NTRS)

    Hruby, R. J.; Cress, S. B.; Dunn, W. R. (Inventor)

    1973-01-01

    The invention relates to an inverted geometry transistor wherein the emitter is buried within the substrate. The transistor can be fabricated as a part of a monolithic integrated circuit and is particularly suited for use in applications where it is desired to employ low actuating voltages. The transistor may employ the same doping levels in the collector and emitter, so these connections can be reversed.

  12. A study on the impact of high penetration distributed generation inverters on grid operation and stability

    NASA Astrophysics Data System (ADS)

    Gu, Fei; Brouwer, Jack; Samuelsen, Scott

    2013-09-01

    Recent advances in inverter technology have enabled ancillary services such as volt/VAR regulation, SCADA communications, and active power filtering. Smart inverters can not only provide real power, but can be controlled to use excess capacity to provide reactive power compensation, power flow control, and active power filtering without supplementary inverter hardware. A transient level inverter model based on the Solectria 7700 inverter is developed and used to assess these control strategies using field data from an existing branch circuit containing two Amonix 68kW CPV-7700 systems installed at the University of California, Irvine.

  13. An inverter/controller subsystem optimized for photovoltaic applications

    NASA Technical Reports Server (NTRS)

    Pickrell, R. L.; Merrill, W. C.; Osullivan, G.

    1978-01-01

    Conversion of solar array dc power to ac power stimulated the specification, design, and simulation testing of an inverter/controller subsystem tailored to the photovoltaic power source characteristics. This paper discusses the optimization of the inverter/controller design as part of an overall Photovoltaic Power System (PPS) designed for maximum energy extraction from the solar array. The special design requirements for the inverter/controller include: (1) a power system controller (PSC) to control continuously the solar array operating point at the maximum power level based on variable solar insolation and cell temperatures; and (2) an inverter designed for high efficiency at rated load and low losses at light loadings to conserve energy. It must be capable of operating connected to the utility line at a level set by an external controller (PSC).

  14. Nanowire NMOS Logic Inverter Characterization.

    PubMed

    Hashim, Yasir

    2016-06-01

    This study is the first to demonstrate characteristics optimization of nanowire N-Channel Metal Oxide Semiconductor (NW-MOS) logic inverter. Noise margins and inflection voltage of transfer characteristics are used as limiting factors in this optimization. A computer-based model used to produce static characteristics of NW-NMOS logic inverter. In this research two circuit configuration of NW-NMOS inverter was studied, in first NW-NMOS circuit, the noise margin for (low input-high output) condition was very low. For second NMOS circuit gives excellent noise margins, and results indicate that optimization depends on applied voltage to the inverter. Increasing gate to source voltage with (2/1) nanowires ratio results better noise margins. Increasing of applied DC load transistor voltage tends to increasing in decreasing noise margins; decreasing this voltage will improve noise margins significantly. PMID:27427653

  15. Inverter Ground Fault Overvoltage Testing

    SciTech Connect

    Hoke, Andy; Nelson, Austin; Chakraborty, Sudipta; Chebahtah, Justin; Wang, Trudie; McCarty, Michael

    2015-08-12

    This report describes testing conducted at NREL to determine the duration and magnitude of transient overvoltages created by several commercial PV inverters during ground fault conditions. For this work, a test plan developed by the Forum on Inverter Grid Integration Issues (FIGII) has been implemented in a custom test setup at NREL. Load rejection overvoltage test results were reported previously in a separate technical report.

  16. 21 CFR 184.1859 - Invert sugar.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Invert sugar. 184.1859 Section 184.1859 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DIRECT FOOD....1859 Invert sugar. (a) Invert sugar (CAS Reg. No. 8013-17-0) is an aqueous solution of inverted...

  17. Orlistat limits cholesterol intestinal absorption by Niemann-pick C1-like 1 (NPC1L1) inhibition.

    PubMed

    Alqahtani, Saeed; Qosa, Hisham; Primeaux, Brian; Kaddoumi, Amal

    2015-09-01

    The known mechanism by which orlistat decreases the absorption of dietary cholesterol is by inhibition of intestinal lipases. The aim of this study was to investigate the ability of orlistat to limit cholesterol absorption by inhibition of the cholesterol transport protein Niemann-Pick C1-like 1 (NPC1L1) as another mechanism of action. In situ rat intestinal perfusion studies were conducted to study the effect of orlistat on jejunal cholesterol absorption. Inhibition kinetic parameters were calculated from in vitro inhibition studies using Caco2 and NPC1L1 transfected cell lines. The in situ studies demonstrated that intestinal perfusion of orlistat (100µM) was able to reduce cholesterol absorption by three-fold when compared to control (i.e. in the absence of orlistat, P<0.01). In vitro studies using Caco2 cells demonstrated orlistat to reduce the cellular uptake of cholesterol by 30%. Additionally, orlistat reduced the cellular uptake of cholesterol in dose dependent manner in NPC1L1 transfected cell line with an IC50=1.2µM. Lineweaver-Burk plot indicated a noncompetitive inhibition of NPC1L1 by orlistat. Beside the already established mechanism by which orlistat reduces the absorption of cholesterol, we demonstrated for the first time that orlistat limits cholesterol absorption by the inhibition of NPC1L1 transport protein. PMID:26048312

  18. A Nup133-dependent NPC-anchored network tethers centrosomes to the nuclear envelope in prophase

    PubMed Central

    Bolhy, Stéphanie; Bouhlel, Imène; Dultz, Elisa; Nayak, Tania; Zuccolo, Michela; Gatti, Xavier; Vallee, Richard; Ellenberg, Jan

    2011-01-01

    Centrosomes are closely associated with the nuclear envelope (NE) throughout the cell cycle and this association is maintained in prophase when they separate to establish the future mitotic spindle. At this stage, the kinetochore constituents CENP-F, NudE, NudEL, dynein, and dynactin accumulate at the NE. We demonstrate here that the N-terminal domain of the nuclear pore complex (NPC) protein Nup133, although largely dispensable for NPC assembly, is required for efficient anchoring of the dynein/dynactin complex to the NE in prophase. Nup133 exerts this function through an interaction network via CENP-F and NudE/EL. We show that this molecular chain is critical for maintaining centrosome association with the NE at mitotic entry and contributes to this process without interfering with the previously described RanBP2–BICD2-dependent pathway of centrosome anchoring. Finally, our study reveals that tethering of centrosomes to the nuclear surface at the G2/M transition contributes, along with other cellular mechanisms, to early stages of bipolar spindle assembly. PMID:21383080

  19. Npc1 deficiency in the C57BL/6J genetic background enhances Niemann-Pick disease type C spleen pathology.

    PubMed

    Parra, Julio; Klein, Andrés D; Castro, Juan; Morales, María Gabriela; Mosqueira, Matías; Valencia, Ilse; Cortés, Victor; Rigotti, Attilio; Zanlungo, Silvana

    2011-09-30

    Niemann-Pick type C (NPC) disease is an autosomal recessive neurovisceral lipid storage disorder. The affected genes are NPC1 and NPC2. Mutations in either gene lead to intracellular cholesterol accumulation. There are three forms of the disease, which are categorized based on the onset and severity of the disease: the infantile form, in which the liver and spleen are severely affected, the juvenile form, in which the liver and brain are affected, and the adult form, which affects the brain. In mice, a spontaneous mutation in the Npc1 gene originated in the BALB/c inbred strain mimics the juvenile form of the disease. To study the influence of genetic background on the expression of NPC disease in mice, we transferred the Npc1 mutation from the BALB/c to C57BL/6J inbred background. We found that C57BL/6J-Npc1(-/-) mice present with a much more aggressive form of the disease, including a shorter lifespan than BALB/c-Npc1(-/-) mice. Surprisingly, there was no difference in the amount of cholesterol in the brains of Npc1(-/-) mice of either mouse strain. However, Npc1(-/-) mice with the C57BL/6J genetic background showed striking spleen damage with a marked buildup of cholesterol and phospholipids at an early age, which correlated with large foamy cell clusters. In addition, C57BL/6J Npc1(-/-) mice presented red cell abnormalities and abundant ghost erythrocytes that correlated with a lower hemoglobin concentration. We also found abnormalities in white cells, such as cytoplasmic granulation and neutrophil hypersegmentation that included lymphopenia and atypias. In conclusion, Npc1 deficiency in the C57BL6/J background is associated with spleen, erythrocyte, and immune system abnormalities that lead to a reduced lifespan. PMID:21910975

  20. All-trans retinoic acid-triggered antimicrobial activity against Mycobacterium tuberculosis is dependent on NPC2.

    PubMed

    Wheelwright, Matthew; Kim, Elliot W; Inkeles, Megan S; De Leon, Avelino; Pellegrini, Matteo; Krutzik, Stephan R; Liu, Philip T

    2014-03-01

    A role for vitamin A in host defense against Mycobacterium tuberculosis has been suggested through epidemiological and in vitro studies; however, the mechanism is unclear. In this study, we demonstrate that vitamin A-triggered antimicrobial activity against M. tuberculosis requires expression of NPC2. Comparison of monocytes stimulated with all-trans retinoic acid (ATRA) or 1,25-dihydroxyvitamin D3 (1,25D3), the biologically active forms of vitamin A and vitamin D, respectively, indicates that ATRA and 1,25D3 induce mechanistically distinct antimicrobial activities. Stimulation of primary human monocytes with ATRA did not result in expression of the antimicrobial peptide cathelicidin, which is required for 1,25D3 antimicrobial activity. In contrast, ATRA triggered a reduction in the total cellular cholesterol concentration, whereas 1,25D3 did not. Blocking ATRA-induced cellular cholesterol reduction inhibits antimicrobial activity as well. Bioinformatic analysis of ATRA- and 1,25D3-induced gene profiles suggests that NPC2 is a key gene in ATRA-induced cholesterol regulation. Knockdown experiments demonstrate that ATRA-mediated decrease in total cellular cholesterol content and increase in lysosomal acidification are both dependent upon expression of NPC2. Expression of NPC2 was lower in caseous tuberculosis granulomas and M. tuberculosis-infected monocytes compared with normal lung and uninfected cells, respectively. Loss of NPC2 expression ablated ATRA-induced antimicrobial activity. Taken together, these results suggest that the vitamin A-mediated antimicrobial mechanism against M. tuberculosis requires NPC2-dependent expression and function, indicating a key role for cellular cholesterol regulation in the innate immune response. PMID:24501203

  1. Level IIb CTV delineation based on cervical fascia anatomy in nasopharyngeal cancer.

    PubMed

    Zhang, Jun; Pan, Li; Ren, Jing; Lang, Jinyi; Wen, Hao; Wang, Jie; Zhang, Shichuan

    2015-04-01

    We carefully reviewed magnetic resonance (MR) images from 100 consecutive NPC patients and analyzed the lymph node distribution status at level IIb. We proposed several modifications of the existing consensus guidelines for determining the level IIb clinical target volume (CTV) in NPC patients. PMID:25770873

  2. Characterization of a Spontaneous Novel Mutation in the NPC2 Gene in a Cat Affected by Niemann Pick Type C Disease

    PubMed Central

    Zampieri, Stefania; Bianchi, Ezio; Cantile, Carlo; Saleri, Roberta; Bembi, Bruno; Dardis, Andrea

    2014-01-01

    Niemann-Pick C disease (NPC) is an autosomal recessive lysosomal storage disorder characterized by accumulation of unesterified cholesterol and other lipids within the lysosomes due to mutation in NPC1 or NPC2 genes. A feline model of NPC carrying a mutation in NPC1 gene has been previously described. We have identified two kittens affected by NPC disease due to a mutation in NPC2 gene. They manifested with tremors at the age of 3 months, which progressed to dystonia and severe ataxia. At 6 months of age cat 2 was unable to stand without assistance and had bilaterally reduced menace response. It died at the age of 10 months. Post-mortem histological analysis of the brain showed the presence of neurons with cytoplasmic swelling and vacuoles, gliosis of the substantia nigra and degeneration of the white matter. Spheroids with accumulation of ubiquitinated aggregates were prominent in the cerebellar cortex. Purkinje cells were markedly reduced in number and they showed prominent intracytoplasmic storage. Scattered perivascular aggregates of lymphocytes and microglial cells proliferation were present in the thalamus and midbrain. Proliferation of Bergmann glia was also observed. In the liver, hepatocytes were swollen because of accumulation of small vacuoles and foamy Kupffer cells were also detected. Foamy macrophages were observed within the pulmonary interstitium and alveoli as well. At 9 months cat 1 was unable to walk, developed seizures and it was euthanized at 21 months. Filipin staining of cultured fibroblasts showed massive storage of unesterified cholesterol. Molecular analysis of NPC1 and NPC2 genes showed the presence of a homozygous intronic mutation (c.82+5G>A) in the NPC2 gene. The subsequent analysis of the mRNA showed that the mutation causes the retention of 105 bp in the mature mRNA, which leads to the in frame insertion of 35 amino acids between residues 28 and 29 of NPC2 protein (p.G28_S29ins35). PMID:25396745

  3. Microgrid and Inverter Control and Simulator Software

    SciTech Connect

    2012-09-13

    A collection of software that can simulate the operation of an inverter on a microgrid or control a real inverter. In addition, it can simulate the control of multiple nodes on a microgrid." Application: Simulation of inverters and microgrids; control of inverters on microgrids." The MMI submodule is designed to control custom inverter hardware, and to simulate that hardware. The INVERTER submodule is only the simulator code, and is of an earlier generation than the simulator in MMI. The MICROGRID submodule is an agent-based simulator of multiple nodes on a microgrid which presents a web interface. The WIND submodule produces movies of wind data with a web interface.

  4. Inverter design for high frequency power distribution

    NASA Technical Reports Server (NTRS)

    King, R. J.

    1985-01-01

    A class of simple resonantly commutated inverters are investigated for use in a high power (100 KW - 1000 KW) high frequency (10 KHz - 20 KHz) AC power distribution system. The Mapham inverter is found to provide a unique combination of large thyristor turn-off angle and good utilization factor, much better than an alternate 'current-fed' inverter. The effects of loading the Mapham inverter entirely with rectifier loads are investigated by simulation and with an experimental 3 KW 20 KHz inverter. This inverter is found to be well suited to a power system with heavy rectifier loading.

  5. Advanced Modular Inverter Technology Development

    SciTech Connect

    Adam Szczepanek

    2006-02-04

    Electric and hybrid-electric vehicle systems require an inverter to convert the direct current (DC) output of the energy generation/storage system (engine, fuel cells, or batteries) to the alternating current (AC) that vehicle propulsion motors use. Vehicle support systems, such as lights and air conditioning, also use the inverter AC output. Distributed energy systems require an inverter to provide the high quality AC output that energy system customers demand. Today's inverters are expensive due to the cost of the power electronics components, and system designers must also tailor the inverter for individual applications. Thus, the benefits of mass production are not available, resulting in high initial procurement costs as well as high inverter maintenance and repair costs. Electricore, Inc. (www.electricore.org) a public good 501 (c) (3) not-for-profit advanced technology development consortium assembled a highly qualified team consisting of AeroVironment Inc. (www.aerovironment.com) and Delphi Automotive Systems LLC (Delphi), (www.delphi.com), as equal tiered technical leads, to develop an advanced, modular construction, inverter packaging technology that will offer a 30% cost reduction over conventional designs adding to the development of energy conversion technologies for crosscutting applications in the building, industry, transportation, and utility sectors. The proposed inverter allows for a reduction of weight and size of power electronics in the above-mentioned sectors and is scalable over the range of 15 to 500kW. The main objective of this program was to optimize existing AeroVironment inverter technology to improve power density, reliability and producibility as well as develop new topology to reduce line filter size. The newly developed inverter design will be used in automotive and distribution generation applications. In the first part of this program the high-density power stages were redesigned, optimized and fabricated. One of the main tasks

  6. Inverting an Introductory Statistics Classroom

    ERIC Educational Resources Information Center

    Kraut, Gertrud L.

    2015-01-01

    The inverted classroom allows more in-class time for inquiry-based learning and for working through more advanced problem-solving activities than does the traditional lecture class. The skills acquired in this learning environment offer benefits far beyond the statistics classroom. This paper discusses four ways that can make the inverted…

  7. Update on SIC-Based Inverter Technology

    SciTech Connect

    Chinthavali, Madhu Sudhan; Zhang, Hui; Tolbert, Leon M; Ozpineci, Burak

    2009-01-01

    This paper presents a study of silicon carbide (SiC) technology which includes device characterization and modeling, inverter simulation, and test results for several prototype inverters. The static and dynamic characteristics of discrete devices and half bridge modules are presented. Test results of a 55 kW hybrid inverter with SiC Schottky diodes and an 18 kW all-SiC inverter using SiC JFETs and Schottky diodes are demonstrated.

  8. Effect of NPC-14686 (Fmoc-l-Homophenylalanine) on Ca²⁺ Homeostasis and Viability in OC2 Human Oral Cancer Cells.

    PubMed

    Li, Yih-Do; Chou, Chiang-Ting; Liang, Wei-Zhe; Tseng, Hui-Wen; Fang, Yi-Chien; Hung, Tzu-Yi; Chang, Hong-Tai; Kuo, Daih-Huang; Kuo, Chun-Chi; Ho, Chin-Man; Shieh, Pochuen; Chen, Fu-An; Jan, Chung-Ren

    2015-10-31

    The effect of the anti-inflammatory compound NPC-14686 on intracellular Ca²⁺ concentration ([Ca²⁺](i)) and viability in OC2 human oral cancer cells was investigated. The Ca²⁺-sensitive fluorescent probe fura-2 was used to examine [Ca²⁺](i). NPC-14686 induced [Ca²⁺](i) rises in a concentration-dependent fashion. The effect was reduced approximately by 10% by removing extracellular Ca²⁺. NPC-14686- elicited Ca²⁺ signal was decreased by nifedipine, econazole, SKF96365, and GF109203X. In Ca²⁺-free medium, incubation with the endoplasmic reticulum Ca²⁺ pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) abolished NPC-14686-induced [Ca²⁺](i) rises. Conversely, pretreatment with NPC-14686 abolished thapsigargin or BHQ-induced [Ca²⁺](i) rises. Inhibition of phospholipase C with U73122 abolished NPC-14686-induced [Ca²⁺](i) rises. At 20-100 μM, NPC-14686 inhibited cell viability, which was not reversed by chelating cytosolic Ca²⁺ with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'- tetraacetic acid-acetoxymethyl ester (BAPTA/AM). NPC-14686 between 20 μM and 40 μM also induced apoptosis. Collectively, in OC2 cells, NPC-14686 induced [Ca²⁺](i) rises by evoking phospholipase C-dependent Ca²⁺ release from the endoplasmic reticulum and Ca²⁺ entry via protein kinase C-regulated store-operated Ca²⁺ channels. NPC-14686 also caused Ca²⁺-independent apoptosis. PMID:26387652

  9. Improved Performance via the Inverted Classroom

    ERIC Educational Resources Information Center

    Weinstein, Randy D.

    2015-01-01

    This study examined student performance in an inverted thermodynamics course (lectures provided by video outside of class) compared to a traditional lecture class. Students in the inverted class performed better on their exams. Students in the bottom third of the inverted course showed the greatest improvement. These bottom third students had a C…

  10. 21 CFR 184.1859 - Invert sugar.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Invert sugar. 184.1859 Section 184.1859 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN... Substances Affirmed as GRAS § 184.1859 Invert sugar. (a) Invert sugar (CAS Reg. No. 8013-17-0) is an...

  11. 21 CFR 184.1859 - Invert sugar.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Invert sugar. 184.1859 Section 184.1859 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN... Substances Affirmed as GRAS § 184.1859 Invert sugar. (a) Invert sugar (CAS Reg. No. 8013-17-0) is an...

  12. 21 CFR 184.1859 - Invert sugar.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Invert sugar. 184.1859 Section 184.1859 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN... Substances Affirmed as GRAS § 184.1859 Invert sugar. (a) Invert sugar (CAS Reg. No. 8013-17-0) is an...

  13. 21 CFR 184.1859 - Invert sugar.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Invert sugar. 184.1859 Section 184.1859 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN... Substances Affirmed as GRAS § 184.1859 Invert sugar. (a) Invert sugar (CAS Reg. No. 8013-17-0) is an...

  14. Thermal Study of Inverter Components: Preprint

    SciTech Connect

    Sorensen, N. R.; Thomas, E. V.; Quintana, M. A.; Barkaszi, S.; Rosenthal, A.; Zhang, Z.; Kurtz, S.

    2012-06-01

    Thermal histories of inverter components were collected from operating inverters from several manufacturers and three locations. The data were analyzed to determine thermal profiles, the dependence on local conditions, and to assess the effect on inverter reliability. Inverter temperatures were shown to increase with the power dissipation of the inverters, follow diurnal and annual cycles, and have a dependence on wind speed. An accumulated damage model was applied to the temperature profiles and an example of using these data to predict reliability was explored.

  15. Evaluation of recent residential inverters

    SciTech Connect

    Nichols, B.E.

    1982-06-01

    Seven residential utility-interactive inverters for photovoltaic power systems have been evaluated at MIT Laboratory and at the Northeast Residential Experiment Station (NE RES). Two, a Windworks Gemini and an Abacus Sunverter, have been reported on previously. Reviewed here are five other inverters: Windworks Gemini 8-kW (dc) model with an ac filter to improve the output current waveform and power factor; Acheval Wind Electronics 10-kW (ac) model, Helionetics 6-kW (dc) model; and American Power Conversion 2-kW and 4-kW (ac) models. Input and output power, power factor, current waveform distortion, audio noise and radio frequency interference measurements were made at the NE RES and the results are presented.

  16. Effective switching frequency multiplier inverter

    SciTech Connect

    Su, Gui-Jia; Peng, Fang Z.

    2007-08-07

    A switching frequency multiplier inverter for low inductance machines that uses parallel connection of switches and each switch is independently controlled according to a pulse width modulation scheme. The effective switching frequency is multiplied by the number of switches connected in parallel while each individual switch operates within its limit of switching frequency. This technique can also be used for other power converters such as DC/DC, AC/DC converters.

  17. The Inverted Snow Globe Shadow

    NASA Astrophysics Data System (ADS)

    Ribeiro, Jair Lúcio Prados

    2015-01-01

    Our high school optics course finishes with an assignment that students usually appreciate. They must take pictures of everyday situations representing optical phenomena such as reflection, refraction, or dispersion, and post them on Instagram.1 When the photos were presented to the class, one student revealed an intriguing photo, similar to Fig. 1, showing a snow globe exposed to sunlight and its inverted shadow. This paper offers an explanation of the problem, which occurs due to light refraction from the globe.

  18. Gripper deploying and inverting linkage

    DOEpatents

    Minichan, Richard L.; Killian, Mark A.

    1993-01-01

    An end effector deploying and inverting linkage. The linkage comprises an air cylinder mounted in a frame or tube, a sliding bracket next to the air cylinder, a stopping bracket depending from the frame and three, pivotally-attached links that are attached to the end effector and to each other in such a way as to be capable of inverting the end effector and translating it laterally. The first of the three links is a straight element that is moved up and down by the shaft of the air cylinder. The second link is attached at one end to the stopping bracket and to the side of the end effector at the other end. The first link is attached near the middle of the second, sharply angled link so that, as the shaft of the air cylinder moves up and down, the second link rotates about an axis perpendicular to the frame and inverts and translates the end effector. The rotation of the second link is stopped at both ends when the link engages stops on the stopping bracket. The third link, slightly angled, is attached to the sliding bracket at one end and to the end of the end effector at the other. The third helps to control the end effector in its motion.

  19. Gripper deploying and inverting linkage

    DOEpatents

    Minichan, R.L.; Killian, M.A.

    1993-03-02

    An end effector deploying and inverting linkage. The linkage comprises an air cylinder mounted in a frame or tube, a sliding bracket next to the air cylinder, a stopping bracket depending from the frame and three, pivotally-attached links that are attached to the end effector and to each other in such a way as to be capable of inverting the end effector and translating it laterally. The first of the three links is a straight element that is moved up and down by the shaft of the air cylinder. The second link is attached at one end to the stopping bracket and to the side of the end effector at the other end. The first link is attached near the middle of the second, sharply angled link so that, as the shaft of the air cylinder moves up and down, the second link rotates about an axis perpendicular to the frame and inverts and translates the end effector. The rotation of the second link is stopped at both ends when the link engages stops on the stopping bracket. The third link, slightly angled, is attached to the sliding bracket at one end and to the end of the end effector at the other. The third helps to control the end effector in its motion.

  20. Three-phase multilevel solar inverter for motor drive system

    NASA Astrophysics Data System (ADS)

    Bhasagare, Mayuresh P.

    This thesis deals with three phase inverters and the different control strategies that can be associated with an inverter being used together. The first part of this thesis discusses the present research in the fields of PV panels, motor drive systems and three phase inverters along with their control. This control includes various strategies like MPPT, Volts-Hertz and modulation index compensation. Incorporating these techniques together is the goal of this thesis. A new topology for operating an open end motor drive system has also been discusses, where a boost converter and a flyback converter have been used in cascade to run a three phase motor. The main advantage of this is increasing the number of levels and improving the quality of the output voltage, not to mention a few other benefits of having the proposed circuit. A new algorithm has also been designed for starting and stopping the motor, which controls the current drawn from the power source during starting.

  1. Suspended Patch Antenna Array With Electromagnetically Coupled Inverted Microstrip Feed

    NASA Technical Reports Server (NTRS)

    Simons, Rainee N.

    2000-01-01

    The paper demonstrates a four-element suspended patch antenna array, with a parasitic patch layer and an electromagnetically coupled inverted microstrip feed, for linear polarization at K-Band frequencies. This antenna has the following advantages over conventional microstrip antennas: First, the inverted microstrip has lower attenuation than conventional microstrip; hence, conductor loss associated with the antenna corporate feed is lower resulting in higher gain and efficiency. Second, conventional proximity coupled patch antennas require a substrate for the feed and a superstrate for the patch. However, the inverted microstrip fed patch antenna makes use of a single substrate, and hence, is lightweight and low cost. Third, electromagnetic coupling results in wider bandwidth. Details regarding the design and fabrication will be presented as well as measured results including return loss, radiation patterns and cross-polarization levels.

  2. Normalization of Cholesterol Homeostasis by 2-Hydroxypropyl-β-cyclodextrin in Neurons and Glia from Niemann-Pick C1 (NPC1)-deficient Mice*

    PubMed Central

    Peake, Kyle B.; Vance, Jean E.

    2012-01-01

    Niemann-Pick C (NPC) disease is an inherited, progressive neurodegenerative disorder caused by mutations in the NPC1 or NPC2 gene that result in an accumulation of unesterified cholesterol in late endosomes/lysosomes (LE/L) and impaired export of cholesterol from LE/L to the endoplasmic reticulum (ER). Recent studies demonstrate that administration of cyclodextrin (CD) to Npc1−/− mice eliminates cholesterol sequestration in LE/L of many tissues, including the brain, delays neurodegeneration, and increases lifespan of the mice. We have now investigated cholesterol homeostasis in NPC1-deficient cells of the brain in response to CD. Primary cultures of neurons and glial cells from Npc1−/− mice were incubated for 24 h with 0.1 to 10 mm CD after which survival and cholesterol homeostasis were monitored. Although 10 mm CD was profoundly neurotoxic, and altered astrocyte morphology, 0.1 and 1 mm CD were not toxic but effectively mobilized stored cholesterol from the LE/L as indicated by filipin staining. However, 0.1 and 1 mm CD altered cholesterol homeostasis in opposite directions. The data suggest that 0.1 mm CD releases cholesterol trapped in LE/L of neurons and astrocytes and increases cholesterol availability at the ER, whereas 1 mm CD primarily extracts cholesterol from the plasma membrane and reduces ER cholesterol. These studies in Npc1−/− neurons and astrocytes establish a dose of CD (0.1 mm) that would likely be beneficial in NPC disease. The findings are timely because treatment of NPC disease patients with CD is currently being initiated. PMID:22277650

  3. Identification of NPC1 as the target of U18666A, an inhibitor of lysosomal cholesterol export and Ebola infection.

    PubMed

    Lu, Feiran; Liang, Qiren; Abi-Mosleh, Lina; Das, Akash; De Brabander, Jef K; Goldstein, Joseph L; Brown, Michael S

    2015-01-01

    Niemann-Pick C1 (NPC1) is a lysosomal membrane protein that exports cholesterol derived from receptor-mediated uptake of LDL, and it also mediates cellular entry of Ebola virus. Cholesterol export is inhibited by nanomolar concentrations of U18666A, a cationic sterol. To identify the target of U18666A, we synthesized U-X, a U18666A derivative with a benzophenone that permits ultraviolet-induced crosslinking. When added to CHO cells, U-X crosslinked to NPC1. Crosslinking was blocked by U18666A derivatives that block cholesterol export, but not derivatives lacking blocking activity. Crosslinking was prevented by point mutation in the sterol-sensing domain (SSD) of NPC1, but not by point mutation in the N-terminal domain (NTD). These data suggest that the SSD contains a U18666A-inhibitable site required for cholesterol export distinct from the cholesterol-binding site in the NTD. Inasmuch as inhibition of Ebola requires 100-fold higher concentrations of U18666A, the high affinity U16888A-binding site is likely not required for virus entry. PMID:26646182

  4. Identification of NPC1 as the target of U18666A, an inhibitor of lysosomal cholesterol export and Ebola infection

    PubMed Central

    Lu, Feiran; Liang, Qiren; Abi-Mosleh, Lina; Das, Akash; De Brabander, Jef K; Goldstein, Joseph L; Brown, Michael S

    2015-01-01

    Niemann-Pick C1 (NPC1) is a lysosomal membrane protein that exports cholesterol derived from receptor-mediated uptake of LDL, and it also mediates cellular entry of Ebola virus. Cholesterol export is inhibited by nanomolar concentrations of U18666A, a cationic sterol. To identify the target of U18666A, we synthesized U-X, a U18666A derivative with a benzophenone that permits ultraviolet-induced crosslinking. When added to CHO cells, U-X crosslinked to NPC1. Crosslinking was blocked by U18666A derivatives that block cholesterol export, but not derivatives lacking blocking activity. Crosslinking was prevented by point mutation in the sterol-sensing domain (SSD) of NPC1, but not by point mutation in the N-terminal domain (NTD). These data suggest that the SSD contains a U18666A-inhibitable site required for cholesterol export distinct from the cholesterol-binding site in the NTD. Inasmuch as inhibition of Ebola requires 100-fold higher concentrations of U18666A, the high affinity U16888A-binding site is likely not required for virus entry. DOI: http://dx.doi.org/10.7554/eLife.12177.001 PMID:26646182

  5. Repetition probability effects for inverted faces.

    PubMed

    Grotheer, Mareike; Hermann, Petra; Vidnyánszky, Zoltán; Kovács, Gyula

    2014-11-15

    It has been shown, that the repetition related reduction of the blood-oxygen level dependent (BOLD) signal is modulated by the probability of repetitions (P(rep)) for faces (Summerfield et al., 2008), providing support for the predictive coding (PC) model of visual perception (Rao and Ballard, 1999). However, the stage of face processing where repetition suppression (RS) is modulated by P(rep) is still unclear. Face inversion is known to interrupt higher level configural/holistic face processing steps and if modulation of RS by P(rep) takes place at these stages of face processing, P(rep) effects are expected to be reduced for inverted when compared to upright faces. Therefore, here we aimed at investigating whether P(rep) effects on RS observed for face stimuli originate at the higher-level configural/holistic stages of face processing by comparing these effects for upright and inverted faces. Similarly to previous studies, we manipulated P(rep) for pairs of stimuli in individual blocks of fMRI recordings. This manipulation significantly influenced repetition suppression in the posterior FFA, the OFA and the LO, independently of stimulus orientation. Our results thus reveal that RS in the ventral visual stream is modulated by P(rep) even in the case of face inversion and hence strongly compromised configural/holistic face processing. An additional whole-brain analysis could not identify any areas where the modulatory effect of probability was orientation specific either. These findings imply that P(rep) effects on RS might originate from the earlier stages of face processing. PMID:25123974

  6. Familial inverted duplication 7p

    SciTech Connect

    Schaefer, G.B.; Novak, K.; Steele, D.

    1995-03-27

    A 10-month-old female with developmental delay and failure to thrive was referred for genetic evaluation as part of an adoption assessment. Physical exam showed a mildly beaked nose and clinodactyly, but otherwise nothing remarkable. Chromosome analysis showed an inverted duplication of the p12.2{r_arrow}p13 portion of chromosome 7(46,XX,dup(7)(p13p12.2)). The proposita`s older brother, mother, and grandmother were cognitively delayed and had the same chromosome 7 duplication. A review of the literature showed no other cases involving this exact duplication. 5 refs., 3 figs., 1 tab.

  7. Microgrid and Inverter Control and Simulator Software

    Energy Science and Technology Software Center (ESTSC)

    2012-09-13

    A collection of software that can simulate the operation of an inverter on a microgrid or control a real inverter. In addition, it can simulate the control of multiple nodes on a microgrid." Application: Simulation of inverters and microgrids; control of inverters on microgrids." The MMI submodule is designed to control custom inverter hardware, and to simulate that hardware. The INVERTER submodule is only the simulator code, and is of an earlier generation than themore » simulator in MMI. The MICROGRID submodule is an agent-based simulator of multiple nodes on a microgrid which presents a web interface. The WIND submodule produces movies of wind data with a web interface.« less

  8. Multilevel Inverters for Electric Vehicle Applications

    SciTech Connect

    Habetler, T.G.; Peng, F.Z.; Tolbert, L.M.

    1998-10-22

    This paper presents multilevel inverters as an application for all-electric vehicle (EV) and hybrid-electric vehicle (HEV) motor drives. Diode-clamped inverters and cascaded H-bridge inverters, (1) can generate near-sinusoidal voltages with only fundamental frequency switching; (2) have almost no electromagnetic interference (EMI) and common-mode voltage; and (3) make an EV more accessible/safer and open wiring possible for most of an EV'S power system. This paper explores the benefits and discusses control schemes of the cascade inverter for use as an EV motor drive or a parallel HEV drive and the diode-clamped inverter as a series HEV motor drive. Analytical, simulated, and experimental results show the superiority of these multilevel inverters for this new niche.

  9. System and method for regulating resonant inverters

    DOEpatents

    Stevanovic, Ljubisa Dragoljub; Zane, Regan Andrew

    2007-08-28

    A technique is provided for direct digital phase control of resonant inverters based on sensing of one or more parameters of the resonant inverter. The resonant inverter control system includes a switching circuit for applying power signals to the resonant inverter and a sensor for sensing one or more parameters of the resonant inverter. The one or more parameters are representative of a phase angle. The resonant inverter control system also includes a comparator for comparing the one or more parameters to a reference value and a digital controller for determining timing of the one or more parameters and for regulating operation of the switching circuit based upon the timing of the one or more parameters.

  10. Cascaded H-bridge multilevel inverter for renewable energy generation

    NASA Astrophysics Data System (ADS)

    Pandey, Ravikant; Nath Tripathi, Ravi; Hanamoto, Tsuyoshi

    2016-04-01

    In this paper cascaded H-bridge multilevel inverter (CHBMLI) has been investigated for the application of renewable energy generation. Energy sources like solar, wind, hydro, biomass or combination of these can be manipulated to obtain alternative sources for renewable energy generation. These renewable energy sources have different electrical characteristics like DC or AC level so it is challenging to use generated power by connecting to grid or load directly. The renewable energy source require specific power electronics converter as an interface for conditioning generated power .The multilevel inverter can be utilized for renewable energy sources in two different modes, the power generation mode (stand-alone mode), and compensator mode (statcom). The performance of the multilevel inverter has been compared with two level inverter. In power generation mode CHBMLI supplies the active and reactive power required by the different loads. For operation in compensator mode the indirect current control based on synchronous reference frame theory (SRFT) ensures the grid operating in unity power factor and compensate harmonics and reactive power.

  11. Structure-activity relationship study of non-steroidal NPC1L1 ligands identified through cell-based assay using pharmacological chaperone effect as a readout.

    PubMed

    Karaki, Fumika; Ohgane, Kenji; Fukuda, Hiromitsu; Nakamura, Masahiko; Dodo, Kosuke; Hashimoto, Yuichi

    2014-07-15

    Niemann-Pick type C1-like 1 (NPC1L1) is an intestinal cholesterol transporter that is known to be the target of the cholesterol absorption inhibitor ezetimibe. We previously discovered steroidal NPC1L1 ligands by using a novel cell-based assay that employs pharmacological chaperone effect as a readout. Those steroid derivatives bound to a site different from both the sterol-binding domain and the ezetimibe-binding site, implying that they may be a novel class of NPC1L1 inhibitors with a distinct mode of action. As an extension of that work, we aimed here to find non-steroidal NPC1L1 ligands, which may be better candidates for clinical application than steroidal ligands, by using the same assay to screen our focused library of ligands for liver X receptor (LXR), a nuclear receptor that recognizes oxysterols as endogenous ligands. Here we describe identification of a novel class of NPC1L1 ligands with a ring-fused quinolinone scaffold, and an analysis of the structure-activity relationships of their derivatives as NPC1L1 ligands. PMID:24906511

  12. A single-phase embedded Z-source DC-AC inverter.

    PubMed

    Kim, Se-Jin; Lim, Young-Cheol

    2014-01-01

    In the conventional DC-AC inverter consisting of two DC-DC converters with unipolar output capacitors, the output capacitor voltages of the DC-DC converters must be higher than the DC input voltage. To overcome this weakness, this paper proposes a single-phase DC-AC inverter consisting of two embedded Z-source converters with bipolar output capacitors. The proposed inverter is composed of two embedded Z-source converters with a common DC source and output AC load. Though the output capacitor voltages of the converters are relatively low compared to those of a conventional inverter, an equivalent level of AC output voltages can be obtained. Moreover, by controlling the output capacitor voltages asymmetrically, the AC output voltage of the proposed inverter can be higher than the DC input voltage. To verify the validity of the proposed inverter, experiments were performed with a DC source voltage of 38 V. By controlling the output capacitor voltages of the converters symmetrically or asymmetrically, the proposed inverter can produce sinusoidal AC output voltages. The experiments show that efficiencies of up to 95% and 97% can be achieved with the proposed inverter using symmetric and asymmetric control, respectively. PMID:25133241

  13. A Single-Phase Embedded Z-Source DC-AC Inverter

    PubMed Central

    Kim, Se-Jin; Lim, Young-Cheol

    2014-01-01

    In the conventional DC-AC inverter consisting of two DC-DC converters with unipolar output capacitors, the output capacitor voltages of the DC-DC converters must be higher than the DC input voltage. To overcome this weakness, this paper proposes a single-phase DC-AC inverter consisting of two embedded Z-source converters with bipolar output capacitors. The proposed inverter is composed of two embedded Z-source converters with a common DC source and output AC load. Though the output capacitor voltages of the converters are relatively low compared to those of a conventional inverter, an equivalent level of AC output voltages can be obtained. Moreover, by controlling the output capacitor voltages asymmetrically, the AC output voltage of the proposed inverter can be higher than the DC input voltage. To verify the validity of the proposed inverter, experiments were performed with a DC source voltage of 38 V. By controlling the output capacitor voltages of the converters symmetrically or asymmetrically, the proposed inverter can produce sinusoidal AC output voltages. The experiments show that efficiencies of up to 95% and 97% can be achieved with the proposed inverter using symmetric and asymmetric control, respectively. PMID:25133241

  14. Review of PV Inverter Technology Cost and Performance Projections

    SciTech Connect

    Navigant Consulting Inc.

    2006-01-01

    The National Renewable Energy Laboratory (NREL) has a major responsibility in the implementation of the U.S. Department of Energy's (DOE's) Solar Energy Technologies Program. Sandia National Laboratories (SNL) has a major role in supporting inverter development, characterization, standards, certifications, and verifications. The Solar Energy Technologies Program recently published a Multiyear Technical Plan, which establishes a goal of reducing the Levelized Energy Cost (LEC) for photovoltaic (PV) systems to $0.06/kWh by 2020. The Multiyear Technical Plan estimates that, in order to meet the PV system goal, PV inverter prices will need to decline to $0.25-0.30 Wp by 2020. DOE determined the need to conduct a rigorous review of the PV Program's technical and economic targets, including the target set for PV inverters. NREL requested that Navigant Consulting Inc.(NCI) conduct a review of historical and projected cost and performance improvements for PV inverters, including identification of critical barriers identified and the approaches government might use to address them.

  15. Inverted File Compression through Document Identifier Reassignment.

    ERIC Educational Resources Information Center

    Shieh, Wann-Yun; Chen, Tien-Fu; Shann, Jean Jyh-Jiun; Chung, Chung-Ping

    2003-01-01

    Discusses the use of inverted files in information retrieval systems and proposes a document identifier reassignment method to reduce the average gap values in an inverted file. Highlights include the d-gap technique; document similarity; heuristic algorithms; file compression; and performance evaluation from a simulation environment. (LRW)

  16. Inverted follicular keratosis successfully treated with imiquimod.

    PubMed

    Karadag, Ayse Serap; Ozlu, Emin; Uzuncakmak, Tugba Kevser; Akdeniz, Necmettin; Cobanoglu, Bengu; Oman, Berkant

    2016-01-01

    Inverted follicular keratosis is a rare benign tumor of the follicular infundibulum characterized by exo-endophytic growing. It is thought to be a rare variant of the seborrheic keratosis. The diagnosis of inverted follicular keratosis is generally established histopathologically because clinical differentiation from other lesions is difficult. Herein, we present one such rare case, successfully treated with topical 5% imiquimod cream. PMID:27294052

  17. Circuit controls transients in SCR inverters

    NASA Technical Reports Server (NTRS)

    Moore, E. T.; Wilson, T. G.

    1964-01-01

    Elimination of starting difficulties in SCR inverters is accomplished by the addition of two taps of the output winding of the inverter. On starting or under transient loads, the two additional taps deliver power through diodes without requiring quenching of SCR currents in excess of normal starting load.

  18. Inverted follicular keratosis successfully treated with imiquimod

    PubMed Central

    Karadag, Ayse Serap; Ozlu, Emin; Uzuncakmak, Tugba Kevser; Akdeniz, Necmettin; Cobanoglu, Bengu; Oman, Berkant

    2016-01-01

    Inverted follicular keratosis is a rare benign tumor of the follicular infundibulum characterized by exo-endophytic growing. It is thought to be a rare variant of the seborrheic keratosis. The diagnosis of inverted follicular keratosis is generally established histopathologically because clinical differentiation from other lesions is difficult. Herein, we present one such rare case, successfully treated with topical 5% imiquimod cream. PMID:27294052

  19. Nanostructured Inverted Organic Photovoltaic Cells

    NASA Astrophysics Data System (ADS)

    Thomas, Michael

    Organic photovoltaic cells (OPVs)are promising devices for inexpensive power generation from sunlight. Organic semiconductors, the basic materials for OPVs, can be fabricated using a broad range of fabrication technologies from vapor deposition to solution processing. Upon light absorption, a strongly bound exciton is generated which can diffuse to a donor-acceptor heterojunction. At this interface it can be dissociated into free charge carriers which can be collected by the device electrodes. A major challenge for OPVs are short exciton diffusion lengths of up to 20 nm. Morphology engineering is required in order to harvest the exciton before it recombines and improve OPV performance. This work focuses on the study of nanostructured morphologies for use in inverted architecture OPVs. Glancing angle deposition (GLAD)is employed to fabricate nanocolumnar acceptor films. Through combining these nanostructured C60 films with a conjugated polymer donor P3CBT and a small molecule 3-Q, inverted OPVs are fabricated with the goal to analyze effect of morphology engineering on device performance. A major challenge was that C60 were found to be soluble in most commonly used organic solvents such as dichlorobenzene or chloroform. Although this challenge has limited the donor choice and therefore has limited device performance, a significant effect of morphology engineering could be observed. All GLAD structured C60 OPVs outperformed state of the art architectures such as planar films and bulk heterojunctions fabricated with the same materials. For P3CBT in particular the GLAD structured devices exhibited a twofold increase in power conversion efficiency compared with bulk heterojunctions and a fourfold increase compared with planar devices. In a further study, the acceptor materials PTCDA and C60 were co-evaporated into a single film. PTCDA is stable against non-polar organic solvents while C60 provides a high electron mobility. Nanocolumnar acceptor blended PTCDA:C60 films

  20. Development of a surface micro-machined binary logic inverter for ultra-low frequency MEMS sensor applications

    NASA Astrophysics Data System (ADS)

    Chakraborty, S.; Bhattacharyya, T. K.

    2010-10-01

    This paper presents the development of surface micro-machined binary logic inverter for implementation in low-frequency signal processing applications in MEMS-based sensors. The micro-cantilever switch, which is the fundamental building block of the design, has been designed and optimized with an analytical method and validated with simulation. The working principle of the inverter has been comprehensively worked out. A thorough detail of the design and performance analysis of the inverter has been carried out and it has been verified using system level simulation. The PolyMUMPs surface micro-machining process has been used for implementing and fabricating the MEMS-based digital inverter. The mechanical response and the switching response of the beams used in the inverter have been extensively investigated. Thorough static and dynamic functional characterizations have been carried out on the inverter.

  1. Improved current control makes inverters the power sources of choice

    SciTech Connect

    Yamamoto, H.; Harada, S.; Ueyama, T.

    1997-02-01

    It is now generally understood that by increasing the operating or switching frequency of a power source the size of the main transformer and main reactor can be shrunk. Thus, a 300-A DC welding power source weighing well under 100 lb can be produced. This makes the inverter power source an ideal choice for applications requiring equipment maneuverability. It is also generally understood that due to higher switching frequencies, a smoother output is obtained from inverter power sources. In the late 1980s, the company developed a new double-inverter power source by which inverted DC weld output is inverted back to AC weld output. This product was the first of its kind in the world. Again, the small compact size of this product was of great interest. Utilizing current waveform control, it was realized that fast response switching from electrode negative to electrode positive could be accurately controlled, offering benefits such as AC GTA welding with high-frequency start only, even at a low welding current. The primary benefit is the ability to limit the electrode positive half cycle to less than 5%. The electrode positive half cycle is responsible for tungsten erosion, which also creates the balling effect of a tungsten electrode. By limiting the electrode positive portion of the AC cycle to a very low level, a rather sharp point can be maintained on the tungsten, which creates a very concentrated, focused arc column. This ability provides excellent joint penetration in fillet welding of aluminum alloys, especially on thick plate. It also reduces the heat-affected zone in AC GTA welding of aluminum.

  2. Advances in series resonant inverter technology and its effect on spacecraft employing electric propulsion

    NASA Technical Reports Server (NTRS)

    Robson, R. R.

    1982-01-01

    The efficiency of transistorized Series Resonant Inverters (SRIs), which is higher than that of silicon-controlled rectifier alternatives, reduces spacecraft radiator requirements by 40% and may eliminate the need for heat pipes on 30-cm ion thruster systems. Recently developed 10- and 25-kW inverters have potential applications in gas thrusters, and represent the first spaceborne SRI designs for such power levels. Attention is given to the design and control system approaches employed in these inverter designs to improve efficiency and reduce weight, along with the impact of such improved parameters on electric propulsion systems.

  3. Static Characteristics of the Ferroelectric Transistor Inverter

    NASA Technical Reports Server (NTRS)

    Mitchell, Cody; Laws, crystal; MacLeond, Todd C.; Ho, Fat D.

    2010-01-01

    The inverter is one of the most fundamental building blocks of digital logic, and it can be used as the foundation for understanding more complex logic gates and circuits. This paper presents the characteristics of an inverter circuit using a ferroelectric field-effect transistor. The voltage transfer characteristics are analyzed with respect to varying parameters such as supply voltage, input voltage, and load resistance. The effects of the ferroelectric layer between the gate and semiconductor are examined, and comparisons are made between the inverters using ferroelectric transistors and those using traditional MOSFETs.

  4. Inverted spectra of SWCNT films

    NASA Astrophysics Data System (ADS)

    Lehman, John; Hurst, Katherine; Roberson, Lara; Nield, Kathryn; Hamlin, John

    2008-03-01

    Diffuse Reflectance for purified single wall carbon nanotube (SWCNT) films and its relation to absorptance in the wavelength range 0.6 μm to 2 μm are inverted when compared to absorptivity data in the literature. This surprising behavior has been corroborated by diffuse reflectance measurements and shows that the reflectance is a substantial part of the unique optical behavior. Typically, the absorptance is fairly assumed to be complementary to the transmittance, while the reflectivity is insignificant. Only in certain instances (see for example, Barnes, et. al[1], Wang, et. al[2]), is the small reflectance explicitly accounted for. In the present work, we present diffuse reflectance and specular absorptance at normal incidence of SWCNT films. [1] T. M. Barnes, J. van de Lagemaat, D. Levi,1 G. Rumbles, T. J. Coutts, C. L. Weeks, D. A. Britz, I. Levitsky, J. Peltola, P. Glatkowski, Phys. Rev. B 75, 235410 (2007). [2] F. Wang, M. Y. Sfeir, L. Huang, X. M. H. Huang, Wu, J. Kim, J. Hone, S. O'Brien, L. E. Brus, T. F. Heinz, PRL 96, 167401 (2006).

  5. A SiC MOSFET Based Inverter for Wireless Power Transfer Applications

    SciTech Connect

    Onar, Omer C; Chinthavali, Madhu Sudhan; Campbell, Steven L; Ning, Puqi; White, Cliff P; Miller , John M.

    2014-01-01

    In a wireless power transfer (WPT) system, efficiency of the power conversion stages is crucial so that the WPT technology can compete with the conventional conductive charging systems. Since there are 5 or 6 power conversion stages, each stage needs to be as efficient as possible. SiC inverters are crucial in this case; they can handle high frequency operation and they can operate at relatively higher temperatures resulting in reduces cost and size for the cooling components. This study presents the detailed power module design, development, and fabrication of a SiC inverter. The proposed inverter has been tested at three center frequencies that are considered for the WPT standardization. Performance of the inverter at the same target power transfer level is analyzed along with the other system components. In addition, another SiC inverter has been built in authors laboratory by using the ORNL designed and developed SiC modules. It is shown that the inverter with ORNL packaged SiC modules performs simular to that of the inverter having commercially available SiC modules.

  6. Removing Barriers to Utility Interconnected Photovoltaic Inverters

    SciTech Connect

    Gonzalez, S.; Bonn, R.H.; Ginn, J.W.

    2000-10-03

    The Million Solar Roofs Initiative has motivated a renewed interest in the development of utility interconnected photovoltaic (UIPV) inverters. Government-sponsored programs (PVMaT, PVBONUS) and competition among utility interconnected inverter manufacturers have stimulated innovations and improved the performance of existing technologies. With this resurgence, Sandia National Laboratories (SNL) has developed a program to assist industry initiatives to overcome barriers to UIPV inverters. In accordance with newly adopted IEEE 929-2000, the utility interconnected PV inverters are required to cease energizing the utility grid when either a significant disturbance occurs or the utility experiences an interruption in service. Compliance with IEEE 929-2000 is being widely adopted by utilities as a minimum requirement for utility interconnection. This report summarizes work done at the SNL balance-of-systems laboratory to support the development of IEEE 929-2000 and to assist manufacturers in meeting its requirements.

  7. Integrated Inverter For Driving Multiple Electric Machines

    DOEpatents

    Su, Gui-Jia [Knoxville, TN; Hsu, John S [Oak Ridge, TN

    2006-04-04

    An electric machine drive (50) has a plurality of inverters (50a, 50b) for controlling respective electric machines (57, 62), which may include a three-phase main traction machine (57) and two-phase accessory machines (62) in a hybrid or electric vehicle. The drive (50) has a common control section (53, 54) for controlling the plurality of inverters (50a, 50b) with only one microelectronic processor (54) for controlling the plurality of inverters (50a, 50b), only one gate driver circuit (53) for controlling conduction of semiconductor switches (S1-S10) in the plurality of inverters (50a, 50b), and also includes a common dc bus (70), a common dc bus filtering capacitor (C1) and a common dc bus voltage sensor (67). The electric machines (57, 62) may be synchronous machines, induction machines, or PM machines and may be operated in a motoring mode or a generating mode.

  8. Inverted liver with suprahepatic, anteriorly displaced gallbladder.

    PubMed

    Hibbs, Harold; Ahmad, Usman

    2010-01-01

    A suprahepatic, anteriorly displaced gallbladder in association with an inverted liver is an extremely rare congenital anomaly. We report the clinical and radiologic findings associated with a 78-year-old woman presenting with shortness of breath, desaturation, hypercapnia and hypoxemia. An abnormal chest radiograph demonstrated right hemi-diaphragmatic elevation consistent with a possible eventration. Subsequent imaging by computed tomography (CT) demonstrated an inverted liver with an anteriorly displaced, suprahepatic gallbladder. PMID:20666167

  9. Base drive for paralleled inverter systems

    NASA Technical Reports Server (NTRS)

    Nagano, S. (Inventor)

    1980-01-01

    In a paralleled inverter system, a positive feedback current derived from the total current from all of the modules of the inverter system is applied to the base drive of each of the power transistors of all modules, thereby to provide all modules protection against open or short circuit faults occurring in any of the modules, and force equal current sharing among the modules during turn on of the power transistors.

  10. Automatic load sharing in inverter modules

    NASA Technical Reports Server (NTRS)

    Nagano, S.

    1979-01-01

    Active feedback loads transistor equally with little power loss. Circuit is suitable for balancing modular inverters in spacecraft, computer power supplies, solar-electric power generators, and electric vehicles. Current-balancing circuit senses differences between collector current for power transistor and average value of load currents for all power transistors. Principle is effective not only in fixed duty-cycle inverters but also in converters operating at variable duty cycles.

  11. Work Station For Inverting Solar Cells

    NASA Technical Reports Server (NTRS)

    Feder, H.; Frasch, W.

    1982-01-01

    Final work station along walking-beam conveyor of solar-array assembly line turns each pretabbed solar cell over, depositing it back-side-up onto landing pad, which centers cell without engaging collector surface. Solar cell arrives at inverting work station collector-side-up with two interconnect tabs attached to collector side. Cells are inverted so that second soldering operation takes place in plain view of operator. Inversion protects collector from damage when handled at later stages of assembly.

  12. Theoretical investigation of the oceanic inverted barometer response

    NASA Technical Reports Server (NTRS)

    Dickman, S. R.

    1988-01-01

    Dynamic tidal theory is generalized in order to predict the oceanic response to atmospheric pressure variations. The oceans are found to exhibit distinct dynamic behavior when forced at periods less than one week; depending on the harmonic type of forcing, the amplitude of the response can differ by about 20 percent or more from the static response. Even at roughly two months the traditional 'inverted barometer' may not be sufficiently accurate for applications in which detection of long-term sea level trends or vertical crustal motion is the goal. For forcing at periods of order one year the oceanic response differs by at most a few percent from the static (not the inverted barometer) response; thus calculations of meteorological excitation of the annual and Chandler wobbles can employ the static approximation without reservation.

  13. Are Archean lithospheric keels inverted?

    NASA Astrophysics Data System (ADS)

    Percival, J. A.; Pysklywec, R. N.

    2007-02-01

    Post-tectonic granite "blooms" in many Archean cratons manifest widespread crustal melting that cannot be explained by lithosphere removal, considering the long-term buoyancy of Archean cratonic keels and low mantle geotherms indicated by Archean diamondiferous lithosphere. Rather, heat may have been transferred from the mantle through a process of lithosphere inversion, driven by basal tractive forces acting on gravitationally unstable lithosphere. The top-heavy cell comprises eclogitic lower crust ( ρ = 3500 kg/m 3) lying above depleted mantle lithosphere ( ρ = 3300 kg/m 3), whose aggregate density remained less than that of surrounding asthenosphere ( ρ = 3340 kg/m 3). Parameterized numerical models of the inversion process show a > 40 m.y. pulse of maximum 1060 °C temperatures in the lower crust, sufficient to drive anhydrous melting, when overturned basal lithosphere reaches the Moho. In equilibrating to lower lithosphere conditions, the eclogitic cap may have yielded siliceous melts that infiltrated overlying, previously depleted mantle, producing the high Si/Mg characteristic of some cratonic peridotites. P-T paths calculated for the central part of the inverting cell criss-cross the graphite-diamond boundary, explaining development of large diamond crystals through numerous growth increments. The craton stabilization process follows terminal tectonism by about 50 m.y. as a result of initial cooling, eclogite formation and lithosphere stiffening. Related consequences in the crust include low-pressure regional metamorphism and widespread hydrothermal effects including some gold mineralization. Craton stability is attributed to the high strength of the depleted mantle lithosphere, its rectified density profile, and the presence of refractory compositions at the lithosphere-asthenosphere boundary.

  14. Analysis of Niemann-Pick C1-like 1 (NPC1L1) genetic polymorphisms and haplotypes in Chinese Han population.

    PubMed

    Lou, Xiao-Ya; Qin, Chong-Zhen; Bao, Mei-Hua; Hu, Dong-Li; Chen, Feng; Sun, Hong; Chen, Yao; Guo, Dong; Zhang, Wei; Cheng, Yu; Zhou, Hong-Hao

    2015-09-01

    Niemann-Pick C1-like 1 (NPC1L1i) protein is the key transporter responsible for dietary cholesterol absorption. Recent studies indicated that several functional polymorphisms of NPC1L1 were associated with coronary heart disease (CHD) and response to ezetimibe therapy. The aim of the present study was to analyze the allele frequency and haplotype distribution of NPC1L1 polymorphisms in Chinese Hans and to compare them with those of other ethnic populations reported before. Blood samples were collected from 424 unrelated Chinese Hans (246 males and 178 females). Ten NPC1L1 polymorphisms (-762T > C, -133A > G, -18C > A, 1721C > T, 1735C > G, 1764T > C, 1767G > A, 27677T > C, 25342A > C and 28650A > G) were genotyped by direct sequencing or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Among the variants, the minor allele frequency of -762T > C and 1735C > G were 35.0% and 37.0%, respectively. Furthermore, these two polymorphisms were highly linked with a D' value of 0.80. The observed frequencies of two major haplotypes were 59.1% for T-762/C1735 and 30.1% for C-762/G1735, respectively. The frequencies of the rest variants were extremely low (1.8% for - 133G, 1.5% for -18A, 0.9% for 1721T and only 0.2% for 27677C allele, respectively) or even not detected (1764T > C, 1767G > A, 25342A > C and 28650A > G) in our study population. Comparison with other ethnic populations revealed a remarkable genetic variability in the incidences of NPC1L1 polymorphisms. The frequencies of NPC1L1 polymorphisms in Chinese Hans are comparable to Japanese population but totally different from Caucasians, African-Americans and Hispanic individuals. This is the first study to report the ethnic difference in the frequencies of NPC1L1 functional polymorphisms in detail. -762T > C and 1735C > G are two prevalent NPC1L1 variants which need further studies to explore their clinical impact on CHD prevalence and response to ezetimibe therapy in Chinese Hans

  15. Noise from Supersonic Coaxial Jets. Part 3; Inverted Velocity Profile

    NASA Technical Reports Server (NTRS)

    Dahl, Milo D.; Morris, Philip J.

    1997-01-01

    The instability wave noise generation model is used to study the instability waves in the two shear layers of an inverted velocity profile, supersonic, coaxial jet and the noise radiated from the dominant wave. The inverted velocity profile jet has a high speed outer stream surrounding a low speed inner stream and the outer shear layer is always larger than the inner shear layer. The jet mean flows are calculated numerically. The operating conditions are chosen to exemplify the effect of the coaxial jet outer shear layer initial spreading rates. Calculations are made for the stability characteristics in the coaxial jet shear layers and the noise radiated from the instability waves for different operating conditions with the same total thrust, mass flow and exit area as a single reference jet. Results for inverted velocity profile jets indicate that relative maximum instability wave amplitudes and far field peak noise levels can be reduced from that of the reference jet by having higher spreading rates for the outer shear layer, low velocity ratios, and outer streams hotter than the inner stream.

  16. EMPLACEMENT DRIFT INVERT-LOW STEEL EVALUATION

    SciTech Connect

    M. E. Taylor and D. H. Tang

    2000-09-29

    This technical report evaluates and develops options for reducing the amount of steel in the emplacement drift invert. Concepts developed in the ''Invert Configuration and Drip Shield Interface'' were evaluated to determine material properties required for the proposed invert concepts. Project requirements documents prescribe the use of a carbon steel frame for the invert with a granular material of crushed tuff as ballast. The ''Invert Configuration and Drip Shield Interface'' developed three concepts: (1) All-Ballast Invert; (2) Modified Steel Invert with Ballast; and (3) Steel Tie with Ballast Invert. Analysis of the steel frame members, runway beams, and guide beams, for the modified steel invert with ballast, decreased the quantity of steel in the emplacement drift invert, however a substantial steel support frame for the gantry and waste package/pallet assembly is still required. Use of one of the other two concepts appears to be an alternative to the steel frame and each of the concepts uses considerably less steel materials. Analysis of the steel tie with ballast invert shows that the bearing pressure on the ballast under the single steel tie, C 9 x 20, loaded with the waste package/pallet assembly, drip shield, and backfill exceeds the upper bound of the allowable bearing capacity for tuff used in this study. The single tie, C 10 x 20, will also fail for the same loading condition except for the tie length of 4.2 meters and longer. Analysis also shows that with two ties, C 9 or 10 x 20's, the average ballast pressure is less than the allowable bearing capacity. Distributing the waste package/pallet, drip shield, and backfill loads to two steel ties reduces the contact bearing pressure. Modifying the emplacement pallet end beams to a greater width, reducing the tie spacing, and increasing the width of the ties would ensure that the pallet beams are always supported by two steel ties. Further analysis is required to determine compatible tie size and spacing

  17. Origin-Dependent Inverted-Repeat Amplification: Tests of a Model for Inverted DNA Amplification

    PubMed Central

    Brewer, Bonita J.; Payen, Celia; Di Rienzi, Sara C.; Higgins, Megan M.; Ong, Giang; Dunham, Maitreya J.; Raghuraman, M. K.

    2015-01-01

    DNA replication errors are a major driver of evolution—from single nucleotide polymorphisms to large-scale copy number variations (CNVs). Here we test a specific replication-based model to explain the generation of interstitial, inverted triplications. While no genetic information is lost, the novel inversion junctions and increased copy number of the included sequences create the potential for adaptive phenotypes. The model—Origin-Dependent Inverted-Repeat Amplification (ODIRA)—proposes that a replication error at pre-existing short, interrupted, inverted repeats in genomic sequences generates an extrachromosomal, inverted dimeric, autonomously replicating intermediate; subsequent genomic integration of the dimer yields this class of CNV without loss of distal chromosomal sequences. We used a combination of in vitro and in vivo approaches to test the feasibility of the proposed replication error and its downstream consequences on chromosome structure in the yeast Saccharomyces cerevisiae. We show that the proposed replication error—the ligation of leading and lagging nascent strands to create “closed” forks—can occur in vitro at short, interrupted inverted repeats. The removal of molecules with two closed forks results in a hairpin-capped linear duplex that we show replicates in vivo to create an inverted, dimeric plasmid that subsequently integrates into the genome by homologous recombination, creating an inverted triplication. While other models have been proposed to explain inverted triplications and their derivatives, our model can also explain the generation of human, de novo, inverted amplicons that have a 2:1 mixture of sequences from both homologues of a single parent—a feature readily explained by a plasmid intermediate that arises from one homologue and integrates into the other homologue prior to meiosis. Our tests of key features of ODIRA lend support to this mechanism and suggest further avenues of enquiry to unravel the origins of

  18. Addressable inverter matrix for process and device characterization

    NASA Technical Reports Server (NTRS)

    Buehler, M. G.; Sayah, H. R.

    1985-01-01

    The addressable inverter matrix consists of 222 inverters each accessible with the aid of a shift register. The structure has proven useful in characterizing the variability of inverter transfer curves and in diagnosing processing faults. For good 3-micron CMOS bulk inverters investigated, the percent standard deviation of the inverter threshold voltage was less than one percent and the inverter gain (the slope of the inverter transfer curve at the inverter threshold vltage) was less than 3 percent. The average noise margin for the inverters was near 2 volts for a power supply voltage of 5 volts. The specific faults studied included undersize pull-down transistor widths and various open contacts in the matrix.

  19. Addressable inverter matrix for process and device characterization

    NASA Technical Reports Server (NTRS)

    Buehler, M. G.; Sayah, H. R.

    1985-01-01

    The addressable inverter matrix consists of 222 inverters each accessible with the aid of a shift register. The structure has proven useful in characterizing the variability of inverter transfer curves and in diagnosing processing faults. For good 3-micron CMOS bulk inverters investigated in this study, the percent standard deviation of the inverter threshold voltage was less than one percent and the inverter gain (the slope of the inverter transfer curve at the inverter threshold voltage) was less than 3 percent. The average noise margin for the inverters was near 2 volts for a power supply voltage of 5 volts. The specific faults studied included undersize pull-down transistor widths and various open contacts in the matrix.

  20. An SCR inverter for electric vehicles

    NASA Technical Reports Server (NTRS)

    Latos, T.; Bosack, D.; Ehrlich, R.; Jahns, T.; Mezera, J.; Thimmesch, D.

    1980-01-01

    An inverter for an electric vehicle propulsion application has been designed and constructed to excite a polyphase induction motor from a fixed propulsion battery source. The inverter, rated at 35kW peak power, is fully regenerative and permits vehicle operation in both the forward and reverse directions. Thyristors are employed as the power switching devices arranged in a dc bus commutated topology. This paper describes the major role the controller plays in generating the motor excitation voltage and frequency to deliver performance similar to dc systems. Motoring efficiency test data for the controller are presented. It is concluded that an SCR inverter in conjunction with an ac induction motor is a viable alternative to present dc vehicle propulsion systems on the basis of performance and size criteria.

  1. DC-AC Cascaded H-Bridge Multilevel Boost Inverter With No Inductors for Electric/Hybrid Electric Vehicle Applications

    SciTech Connect

    Tolbert, Leon M; Ozpineci, Burak; Du, Zhong; Chiasson, John N

    2009-01-01

    This paper presents a cascaded H-bridge multilevel boost inverter for electric vehicle (EV) and hybrid EV (HEV) applications implemented without the use of inductors. Currently available power inverter systems for HEVs use a dc-dc boost converter to boost the battery voltage for a traditional three-phase inverter. The present HEV traction drive inverters have low power density, are expensive, and have low efficiency because they need a bulky inductor. A cascaded H-bridge multilevel boost inverter design for EV and HEV applications implemented without the use of inductors is proposed in this paper. Traditionally, each H-bridge needs a dc power supply. The proposed design uses a standard three-leg inverter (one leg for each phase) and an H-bridge in series with each inverter leg which uses a capacitor as the dc power source. A fundamental switching scheme is used to do modulation control and to produce a five-level phase voltage. Experiments show that the proposed dc-ac cascaded H-bridge multilevel boost inverter can output a boosted ac voltage without the use of inductors.

  2. A diagonally inverted LU implicit multigrid scheme

    NASA Technical Reports Server (NTRS)

    Yokota, Jeffrey W.; Caughey, David A.; Chima, Rodrick V.

    1988-01-01

    A new Diagonally Inverted LU Implicit scheme is developed within the framework of the multigrid method for the 3-D unsteady Euler equations. The matrix systems that are to be inverted in the LU scheme are treated by local diagonalizing transformations that decouple them into systems of scalar equations. Unlike the Diagonalized ADI method, the time accuracy of the LU scheme is not reduced since the diagonalization procedure does not destroy time conservation. Even more importantly, this diagonalization significantly reduces the computational effort required to solve the LU approximation and therefore transforms it into a more efficient method of numerically solving the 3-D Euler equations.

  3. Vigilance and task load - In search of the inverted U

    NASA Technical Reports Server (NTRS)

    Wiener, E. L.; Curry, R. E.; Faustina, M. L.

    1984-01-01

    The 'Inverted-U Hypothesis' states that for a given task, there is an optimal level of workload or demand that yields the highest level of performance. A departure in either direction will result in a monotonically lower performance level, hence an inverted-U-shaped relationship between task demand and quality of performance. Most studies to date have failed to demonstrate the left-hand branch of the curve, that is, the regime in which performance presumably rises as load increases. The purpose of this study was to explore whether low-level additional demand on the monitor would result in improved performance. Four groups of subjects performed a visual monitoring task for 48 min, then two of the four groups were given additional tasks, and a third had potentially distracting information on its display. Results indicated that the two groups with additional demand detected more signals than did the control group or the control-plus-distraction group. There were no significant differences in false alarms.

  4. High voltage series resonant inverter ion engine screen supply. [SCR series resonant inverter for space applications

    NASA Technical Reports Server (NTRS)

    Biess, J. J.; Inouye, L. Y.; Shank, J. H.

    1974-01-01

    A high-voltage, high-power LC series resonant inverter using SCRs has been developed for an Ion Engine Power Processor. The inverter operates within 200-400Vdc with a maximum output power of 2.5kW. The inverter control logic, the screen supply electrical and mechanical characteristics, the efficiency and losses in power components, regulation on the dual feedback principle, the SCR waveforms and the component weight are analyzed. Efficiency of 90.5% and weight density of 4.1kg/kW are obtained.

  5. Inverters for interfacing of solar cells with the power grid

    NASA Astrophysics Data System (ADS)

    Karamanzanis, G. N.; Jackson, R. D.

    In this work, based on a research course in the Engineering Dep. Cambridge University, some non-classical inverter circuits are studied. They can be used for interfacing solar cells with the power grid at low voltage (230V) and at low power level. They are based on d.c. choppers which have a fast switching transistor. Their theoretical efficiency is 100 percent and they provide a satisfactory output current waveform in phase to the a.c. line voltage. The problems of control are also studied using a suitable mathematical model.

  6. Electrical characterization of a Mapham inverter using pulse testing techniques

    NASA Technical Reports Server (NTRS)

    Baumann, E. D.; Myers, I. T.; Hammoud, A. N.

    1990-01-01

    The use of a multiple pulse testing technique to determine the electrical characteristics of large megawatt-level power systems for aerospace missions is proposed. An innovative test method based on the multiple pulse technique is demonstrated on a 2-kW Mapham inverter. The concept of this technique shows that characterization of large power systems under electrical equilibrium at rated power can be accomplished without large costly power supplies. The heat generation that occurs in systems when tested in a continuous mode is eliminated. The results indicate that there is a good agreement between this testing technique and that of steady state testing.

  7. Electrical characterization of a Mapham inverter using pulse testing techniques

    NASA Astrophysics Data System (ADS)

    Baumann, E. D.; Myers, I. T.; Hammoud, A. N.

    The use of a multiple pulse testing technique to determine the electrical characteristics of large megawatt-level power systems for aerospace missions is proposed. An innovative test method based on the multiple pulse technique is demonstrated on a 2-kW Mapham inverter. The concept of this technique shows that characterization of large power systems under electrical equilibrium at rated power can be accomplished without large costly power supplies. The heat generation that occurs in systems when tested in a continuous mode is eliminated. The results indicate that there is a good agreement between this testing technique and that of steady state testing.

  8. A Prefix Trie Index for Inverted Files.

    ERIC Educational Resources Information Center

    Nelson, Michael J.

    1997-01-01

    Applies a prefix trie index, or trie hashing, to the problem of providing fast search times, fast load times, and fast update properties in a bibliographic or full-text retrieval system with inverted files. Statistics are given for a test database consisting of an online catalog at the University of Western Ontario. (Author/LRW)

  9. Dynamic maneuvers with a mobile inverted pendulum

    NASA Astrophysics Data System (ADS)

    Pogue, Edward

    A mobile inverted pendulum (MIP) type robot was constructed to test the feasibility of performing high speed, dynamic maneuvers. Techniques were developed for line following and to achieve high speed motion with a MIP. The results indicate that the speeds necessary for the maneuver can be achieved, and the groundwork is laid for further experimentation.

  10. Two-Stage Series-Resonant Inverter

    NASA Technical Reports Server (NTRS)

    Stuart, Thomas A.

    1994-01-01

    Two-stage inverter includes variable-frequency, voltage-regulating first stage and fixed-frequency second stage. Lightweight circuit provides regulated power and is invulnerable to output short circuits. Does not require large capacitor across ac bus, like parallel resonant designs. Particularly suitable for use in ac-power-distribution system of aircraft.

  11. Inverter Matrix for the Clementine Mission

    NASA Technical Reports Server (NTRS)

    Buehler, M. G.; Blaes, B. R.; Tardio, G.; Soli, G. A.

    1994-01-01

    An inverter matrix test circuit was designed for the Clementine space mission and is built into the RRELAX (Radiation and Reliability Assurance Experiment). The objective is to develop a circuit that will allow the evaluation of the CMOS FETs using a lean data set in the noisy spacecraft environment.

  12. Pulse width modulation inverter with battery charger

    NASA Technical Reports Server (NTRS)

    Slicker, James M. (Inventor)

    1985-01-01

    An inverter is connected between a source of DC power and a three-phase AC induction motor, and a microprocessor-based circuit controls the inverter using pulse width modulation techniques. In the disclosed method of pulse width modulation, both edges of each pulse of a carrier pulse train are equally modulated by a time proportional to sin .theta., where .theta. is the angular displacement of the pulse center at the motor stator frequency from a fixed reference point on the carrier waveform. The carrier waveform frequency is a multiple of the motor stator frequency. The modulated pulse train is then applied to each of the motor phase inputs with respective phase shifts of 120.degree. at the stator frequency. Switching control commands for electronic switches in the inverter are stored in a random access memory (RAM) and the locations of the RAM are successively read out in a cyclic manner, each bit of a given RAM location controlling a respective phase input of the motor. The DC power source preferably comprises rechargeable batteries and all but one of the electronic switches in the inverter can be disabled, the remaining electronic switch being part of a flyback DC-DC converter circuit for recharging the battery.

  13. Pulse width modulation inverter with battery charger

    DOEpatents

    Slicker, James M.

    1985-01-01

    An inverter is connected between a source of DC power and a three-phase AC induction motor, and a microprocessor-based circuit controls the inverter using pulse width modulation techniques. In the disclosed method of pulse width modulation, both edges of each pulse of a carrier pulse train are equally modulated by a time proportional to sin .theta., where .theta. is the angular displacement of the pulse center at the motor stator frequency from a fixed reference point on the carrier waveform. The carrier waveform frequency is a multiple of the motor stator frequency. The modulated pulse train is then applied to each of the motor phase inputs with respective phase shifts of 120.degree. at the stator frequency. Switching control commands for electronic switches in the inverter are stored in a random access memory (RAM) and the locations of the RAM are successively read out in a cyclic manner, each bit of a given RAM location controlling a respective phase input of the motor. The DC power source preferably comprises rechargeable batteries and all but one of the electronic switches in the inverter can be disabled, the remaining electronic switch being part of a "flyback" DC-DC converter circuit for recharging the battery.

  14. The Internet and the Inverted Classroom.

    ERIC Educational Resources Information Center

    Lage, Maureen J.; Platt, Glenn

    2000-01-01

    Describes a Web site that is for an undergraduate principles of microeconomics course and a main component of "The Inverted Classroom" in which lectures take place outside of class. Explains that the Web site is divided into four sections: (1) the classroom; (2) the desk; (3) the coffee shop; and (4) the library. (CMK)

  15. APP overexpression in the absence of NPC1 exacerbates metabolism of amyloidogenic proteins of Alzheimer's disease.

    PubMed

    Maulik, Mahua; Peake, Kyle; Chung, JiYun; Wang, Yanlin; Vance, Jean E; Kar, Satyabrata

    2015-12-15

    Amyloid-β (Aβ) peptides originating from β-amyloid precursor protein (APP) are critical in Alzheimer's disease (AD). Cellular cholesterol levels/distribution can regulate production and clearance of Aβ peptides, albeit with contradictory outcomes. To better understand the relationship between cholesterol homeostasis and APP/Aβ metabolism, we have recently generated a bigenic ANPC mouse line overexpressing mutant human APP in the absence of Niemann-Pick type C-1 protein required for intracellular cholesterol transport. Using this unique bigenic ANPC mice and complementary stable N2a cells, we have examined the functional consequences of cellular cholesterol sequestration in the endosomal-lysosomal system, a major site of Aβ production, on APP/Aβ metabolism and its relation to neuronal viability. Levels of APP C-terminal fragments (α-CTF/β-CTF) and Aβ peptides, but not APP mRNA/protein or soluble APPα/APPβ, were increased in ANPC mouse brains and N2a-ANPC cells. These changes were accompanied by reduced clearance of peptides and an increased level/activity of γ-secretase, suggesting that accumulation of APP-CTFs is due to decreased turnover, whereas increased Aβ levels may result from a combination of increased production and decreased turnover. APP-CTFs and Aβ peptides were localized primarily in early-/late-endosomes and to some extent in lysosomes/autophagosomes. Cholesterol sequestration impaired endocytic-autophagic-lysosomal, but not proteasomal, clearance of APP-CTFs/Aβ peptides. Moreover, markers of oxidative stress were increased in vulnerable brain regions of ANPC mice and enhanced β-CTF/Aβ levels increased susceptibility of N2a-ANPC cells to H2O2-induced toxicity. Collectively, our results show that cellular cholesterol sequestration plays a key role in APP/Aβ metabolism and increasing neuronal vulnerability to oxidative stress in AD-related pathology. PMID:26433932

  16. View of Inverted Siphon crossing Hot Water (or White) Canyon. ...

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

    View of Inverted Siphon crossing Hot Water (or White) Canyon. Looking northeast - Childs-Irving Hydroelectric Project, Irving System, Inverted Siphon, Forest Service Road 708/502, Camp Verde, Yavapai County, AZ

  17. Electrical characterization of a Mapham inverter using pulse testing techniques

    NASA Technical Reports Server (NTRS)

    Baumann, E. D.; Myers, I. T.; Hammond, A. N.

    1990-01-01

    Electric power requirements for aerospace missions have reached megawatt power levels. Within the next few decades, it is anticipated that a manned lunar base, interplanetary travel, and surface exploration of the Martian surface will become reality. Several research and development projects aimed at demonstrating megawatt power level converters for space applications are currently underway at the NASA Lewis Research Center. Innovative testing techniques will be required to evaluate the components and converters, when developed, at their rated power in the absence of costly power sources, loads, and cooling systems. Facilities capable of testing these components and systems at full power are available, but their use may be cost prohibitive. The use of a multiple pulse testing technique is proposed to determine the electrical characteristics of large megawatt level power systems. Characterization of a Mapham inverter is made using the proposed technique and conclusions are drawn concerning its suitability as an experimental tool to evaluate megawatt level power systems.

  18. Niemann-Pick disease type C1(NPC1) is involved in resistance against imatinib in the imatinib-resistant Ph+ acute lymphoblastic leukemia cell line SUP-B15/RI.

    PubMed

    Naren, Duolan; Wu, Jiahui; Gong, Yuping; Yan, Tianyou; Wang, Ke; Xu, Wenming; Yang, Xi; Shi, Fangfang; Shi, Rui

    2016-03-01

    Niemann-Pick disease type C1 (NPC1) is involved in cholesterol trafficking and may normally function as a transmembrane efflux pump. Previous studies showed that its dysfunction can lead to cholesterol and daunorubicin accumulation in the cytoplasmic endosomal/lysosomal system, lead to Niemann-Pick disease and resistance to anticancer drugs. In the present study, NPC1 was shown by microarray analysis to be more highly expressed in the Ph+ acute lymphoblastic leukemia cell line SUP-B15/RI, an imatinib-resistant variant of SUP-B15/S cells without bcr-abl gene mutation established in our lab. Further investigation revealed a defect in the functional capacity of the NPC1 protein demonstrated by filipin staining accompanied by a lower intracellular imatinib mesylate(IM) concentration by high-performance liquid chromatography in SUP-B15/RI compared with SUP-B15/S cells. Furthermore, U18666A, an inhibitor of NPC1 function, was used to block cholesterol trafficking to imitate the NPC1 defect in SUP-B15/S cells, leading to higher NPC1 expression, stronger filipin fluorescence, lower intracellular IM concentrations and greater resistance against IM. Samples from non-mutated relapsed Ph+ ALL patients also showed higher NPC1 expression compared with IM-sensitive patients. Our experiment may reveal a new mechanism of IM resistance in Ph+ ALL. PMID:26818574

  19. Japanese power electronics inverter technology and its impact on the American air conditioning industry

    SciTech Connect

    Ushimaru, Kenji.

    1990-08-01

    Since 1983, technological advances and market growth of inverter- driven variable-speed heat pumps in Japan have been dramatic. The high level of market penetration was promoted by a combination of political, economic, and trade policies in Japan. A unique environment was created in which the leading domestic industries-- microprocessor manufacturing, compressors for air conditioning and refrigerators, and power electronic devices--were able to direct the development and market success of inverter-driven heat pumps. As a result, leading US variable-speed heat pump manufacturers should expect a challenge from the Japanese producers of power devices and microprocessors. Because of the vertically-integrated production structure in Japan, in contrast to the out-sourcing culture of the United States, price competition at the component level (such as inverters, sensors, and controls) may impact the structure of the industry more severely than final product sales. 54 refs., 47 figs., 1 tab.

  20. Japanese power electronics inverter technology and its impact on the American air conditioning industry

    NASA Astrophysics Data System (ADS)

    Ushimaru, Kenji

    1990-08-01

    Since 1983, technological advances and market growth of inverter-driven variable-speed heat pumps in Japan have been dramatic. The high level of market penetration was promoted by a combination of political, economic, and trade policies in Japan. A unique environment was created in which the leading domestic industries, microprocessor manufacturing, compressors for air conditioning and refrigerators, and power electronic devices, were able to direct the development and market success of inverter-driven heat pumps. As a result, leading U.S. variable-speed heat pump manufacturers should expect a challenge from the Japanese producers of power devices and microprocessors. Because of the vertically-integrated production structure in Japan, in contrast to the out-sourcing culture of the United States, price competition at the component level (such as inverters, sensors, and controls) may impact the structure of the industry more severely than final product sales.

  1. A Soft-Switching Inverter for High-Temperature Advanced Hybrid Electric Vehicle Traction Motor Drives

    SciTech Connect

    Lai, Jason; Yu, Wensong; Sun, Pengwei; Leslie, Scott; Prusia, Duane; Arnet, Beat; Smith, Chris; Cogan, Art

    2012-03-31

    The state-of-the-art hybrid electric vehicles (HEVs) require the inverter cooling system to have a separate loop to avoid power semiconductor junction over temperatures because the engine coolant temperature of 105°C does not allow for much temperature rise in silicon devices. The proposed work is to develop an advanced soft-switching inverter that will eliminate the device switching loss and cut down the power loss so that the inverter can operate at high-temperature conditions while operating at high switching frequencies with small current ripple in low inductance based permanent magnet motors. The proposed tasks also include high-temperature packaging and thermal modeling and simulation to ensure the packaged module can operate at the desired temperature. The developed module will be integrated with the motor and vehicle controller for dynamometer and in-vehicle testing to prove its superiority. This report will describe the detailed technical design of the soft-switching inverters and their test results. The experiments were conducted both in module level for the module conduction and switching characteristics and in inverter level for its efficiency under inductive and dynamometer load conditions. The performance will be compared with the DOE original specification.

  2. Mobile Inverted Constructivism: Education of Interaction Technology in Social Media

    ERIC Educational Resources Information Center

    Chai, Jia-Xiang; Fan, Kuo-Kuang

    2016-01-01

    The combination of social media and invert teaching is a new path to inverting interation technology education and reconstructing the curriculum of context. In this paper, based on the theory of constructivism learning, a model named Mobile Inverted Constructivism (MIC) is provided. Moreover, in view of the functional quality of social media in…

  3. DC-to-AC inverter ratio failure detector

    NASA Technical Reports Server (NTRS)

    Ebersole, T. J.; Andrews, R. E.

    1975-01-01

    Failure detection technique is based upon input-output ratios, which is independent of inverter loading. Since inverter has fixed relationship between V-in/V-out and I-in/I-out, failure detection criteria are based on this ratio, which is simply inverter transformer turns ratio, K, equal to primary turns divided by secondary turns.

  4. Efficient/reliable dc-to-dc inverter circuit

    NASA Technical Reports Server (NTRS)

    Pasciutti, E. R.

    1970-01-01

    Feedback loop, which contains an inductor in series with a saturable reactor, is added to a standard inverter circuit to permit the inverter power transistors to be switched in a controlled and efficient manner. This inverter is applicable where the power source has either high or low impedance properties.

  5. Solution-processed amorphous niobium oxide as a novel electron collection layer for inverted polymer solar cells

    NASA Astrophysics Data System (ADS)

    Hamada, Keisuke; Murakami, Naoya; Tsubota, Toshiki; Ohno, Teruhisa

    2013-10-01

    Amorphous niobium oxide (NbOx) as an electron collection layer in inverted polymer solar cells was prepared by a solution process. The power conversion efficiency of inverted polymer solar cells based on a blend of poly(3-hexylthiophene) and [6,6]-phenyl C61 butyric acid methyl ester was improved to 2.22% by inserting an NbOx layer between the active layer and indium tin oxide electrode. An energy level diagram of component materials in the inverted polymer solar cell indicated that the NbOx layer works as both an electron collection layer and hole blocking layer in polymer solar cells.

  6. High-power, null-type, inverted pendulum thrust stand.

    PubMed

    Xu, Kunning G; Walker, Mitchell L R

    2009-05-01

    This article presents the theory and operation of a null-type, inverted pendulum thrust stand. The thrust stand design supports thrusters having a total mass up to 250 kg and measures thrust over a range of 1 mN to 5 N. The design uses a conventional inverted pendulum to increase sensitivity, coupled with a null-type feature to eliminate thrust alignment error due to deflection of thrust. The thrust stand position serves as the input to the null-circuit feedback control system and the output is the current to an electromagnetic actuator. Mechanical oscillations are actively damped with an electromagnetic damper. A closed-loop inclination system levels the stand while an active cooling system minimizes thermal effects. The thrust stand incorporates an in situ calibration rig. The thrust of a 3.4 kW Hall thruster is measured for thrust levels up to 230 mN. The uncertainty of the thrust measurements in this experiment is +/-0.6%, determined by examination of the hysteresis, drift of the zero offset and calibration slope variation. PMID:19485530

  7. Cholesterol Accumulation Sequesters Rab9 and Disrupts Late Endosome Function in NPC1-deficient Cells*

    PubMed Central

    Ganley, Ian G.; Pfeffer, Suzanne R.

    2013-01-01

    Niemann-Pick type C disease is an autosomal recessive disorder that leads to massive accumulation of cholesterol and glycosphingolipids in late endosomes and lysosomes. To understand how cholesterol accumulation influences late endosome function, we investigated the effect of elevated cholesterol on Rab9-dependent export of mannose 6-phosphate receptors from this compartment. Endogenous Rab9 levels were elevated 1.8-fold in Niemann-Pick type C cells relative to wild type cells, and its half-life increased 1.6-fold, suggesting that Rab9 accumulation is caused by impaired protein turnover. Reduced Rab9 degradation was accompaniedby stabilization on endosome membranes, as shown by a reduction in the capacity of Rab9 for guanine nucleotide dissociation inhibitor-mediated extraction from Niemann-Pick type C membranes. Cholesterol appeared to stabilize Rab9 directly, as liposomes loaded with prenylated Rab9 showed decreased extractability with increasing cholesterol content. Rab9 is likely sequestered in an inactive form on Niemann-Pick type C membranes, as cation-dependent man-nose 6-phosphate receptorswere missorted to the lysosome for degradation, a process that was reversed by overexpression of GFP-tagged Rab9. In addition to using primary fibroblasts isolated from Niemann-Pick type C patients, RNA interference was utilized to recapitulate the disease phenotype in cultured cells, greatly facilitating the analysis of cholesterol accumulation and late endosome function. We conclude that cholesterol contributes directly to the sequestration of Rab9 on Niemann-Pick type C cell membranes, which in turn, disrupts mannose 6-phosphate receptor trafficking. PMID:16644737

  8. The Invertible Double of Elliptic Operators

    NASA Astrophysics Data System (ADS)

    Booss-Bavnbek, Bernhelm; Lesch, Matthias

    2009-02-01

    First, we review the Dirac operator folklore about basic analytic and geometrical properties of operators of Dirac type on compact manifolds with smooth boundary and on closed partitioned manifolds and show how these properties depend on the construction of a canonical invertible double and are related to the concept of the Calderón projection. Then we summarize a recent construction of a canonical invertible double for general first order elliptic differential operators over smooth compact manifolds with boundary. We derive a natural formula for the Calderón projection which yields a generalization of the famous Cobordism Theorem. We provide a list of assumptions to obtain a continuous variation of the Calderón projection under smooth variation of the coefficients. That yields various new spectral flow theorems. Finally, we sketch a research program for confining, respectively closing, the last remaining gaps between the geometric Dirac operator type situation and the general linear elliptic case.

  9. Electronic Document Management Using Inverted Files System

    NASA Astrophysics Data System (ADS)

    Suhartono, Derwin; Setiawan, Erwin; Irwanto, Djon

    2014-03-01

    The amount of documents increases so fast. Those documents exist not only in a paper based but also in an electronic based. It can be seen from the data sample taken by the SpringerLink publisher in 2010, which showed an increase in the number of digital document collections from 2003 to mid of 2010. Then, how to manage them well becomes an important need. This paper describes a new method in managing documents called as inverted files system. Related with the electronic based document, the inverted files system will closely used in term of its usage to document so that it can be searched over the Internet using the Search Engine. It can improve document search mechanism and document save mechanism.

  10. On the uncontrollable damped triple inverted pendulum

    NASA Astrophysics Data System (ADS)

    Su, H.; Woodham, C. A.

    2003-02-01

    In this paper, the controllability of the damped triple inverted pendulum is investigated. The work is concerned with the form of the cancelling pole and zero which appear in the transfer functions of an uncontrollable system, and follows on from earlier work on the damped double inverted pendulum. The investigation considers first the cases where only one of the three arm frictions is non-zero, and then explores the cases when two of the three arm frictions are non-zero. Due to the complexity of this problem, and the difficulties with the symbolic manipulation software, exploratory numerical investigations have been carried out to facilitate the symbolic investigations, all of which are reported here.

  11. Micro-inverter solar panel mounting

    DOEpatents

    Morris, John; Gilchrist, Phillip Charles

    2016-02-02

    Processes, systems, devices, and articles of manufacture are provided. Each may include adapting micro-inverters initially configured for frame-mounting to mounting on a frameless solar panel. This securement may include using an adaptive clamp or several adaptive clamps secured to a micro-inverter or its components, and using compressive forces applied directly to the solar panel to secure the adaptive clamp and the components to the solar panel. The clamps can also include compressive spacers and safeties for managing the compressive forces exerted on the solar panels. Friction zones may also be used for managing slipping between the clamp and the solar panel during or after installation. Adjustments to the clamps may be carried out through various means and by changing the physical size of the clamps themselves.

  12. Invertible linear transformations and the Lie algebras

    NASA Astrophysics Data System (ADS)

    Zhang, Yufeng; Tam, Honwah; Guo, Fukui

    2008-07-01

    With the help of invertible linear transformations and the known Lie algebras, a way to generate new Lie algebras is given. These Lie algebras obtained have a common feature, i.e. integrable couplings of solitary hierarchies could be obtained by using them, specially, the Hamiltonian structures of them could be worked out. Some ways to construct the loop algebras of the Lie algebras are presented. It follows that some various loop algebras are given. In addition, a few new Lie algebras are explicitly constructed in terms of the classification of Lie algebras proposed by Ma Wen-Xiu, which are bases for obtaining new Lie algebras by using invertible linear transformations. Finally, some solutions of a (2 + 1)-dimensional partial-differential equation hierarchy are obtained, whose Hamiltonian form-expressions are manifested by using the quadratic-form identity.

  13. Maskless inverted pyramid texturization of silicon

    PubMed Central

    Wang, Yan; Yang, Lixia; Liu, Yaoping; Mei, Zengxia; Chen, Wei; Li, Junqiang; Liang, Huili; Kuznetsov, Andrej; Xiaolong, Du

    2015-01-01

    We discovered a technical solution of such outstanding importance that it can trigger new approaches in silicon wet etching processing and, in particular, photovoltaic cell manufacturing. The so called inverted pyramid arrays, outperforming conventional pyramid textures and black silicon because of their superior light-trapping and structure characteristics, can currently only be achieved using more complex techniques involving lithography, laser processing, etc. Importantly, our data demonstrate a feasibility of inverted pyramidal texturization of silicon by maskless Cu-nanoparticles assisted etching in Cu(NO3)2 / HF / H2O2 / H2O solutions and as such may have significant impacts on communities of fellow researchers and industrialists. PMID:26035520

  14. Maskless inverted pyramid texturization of silicon.

    PubMed

    Wang, Yan; Yang, Lixia; Liu, Yaoping; Mei, Zengxia; Chen, Wei; Li, Junqiang; Liang, Huili; Kuznetsov, Andrej; Xiaolong, Du

    2015-01-01

    We discovered a technical solution of such outstanding importance that it can trigger new approaches in silicon wet etching processing and, in particular, photovoltaic cell manufacturing. The so called inverted pyramid arrays, outperforming conventional pyramid textures and black silicon because of their superior light-trapping and structure characteristics, can currently only be achieved using more complex techniques involving lithography, laser processing, etc. Importantly, our data demonstrate a feasibility of inverted pyramidal texturization of silicon by maskless Cu-nanoparticles assisted etching in Cu(NO3)2 / HF / H2O2 / H2O solutions and as such may have significant impacts on communities of fellow researchers and industrialists. PMID:26035520

  15. The cholesterol-binding protein NPC2 restrains recruitment of stromal macrophage-lineage cells to early-stage lung tumours.

    PubMed

    Kamata, Tamihiro; Jin, Hong; Giblett, Susan; Patel, Bipin; Patel, Falguni; Foster, Charles; Pritchard, Catrin

    2015-09-01

    The tumour microenvironment is known to play an integral role in facilitating cancer progression at advanced stages, but its function in some pre-cancerous lesions remains elusive. We have used the (V600) (E)BRAF-driven mouse lung model that develop premalignant lesions to understand stroma-tumour interactions during pre-cancerous development. In this model, we have found that immature macrophage-lineage cells (IMCs) producing PDGFA, TGFβ and CC chemokines are recruited to the stroma of premalignant lung adenomas through CC chemokine receptor 1 (CCR1)-dependent mechanisms. Stromal IMCs promote proliferation and transcriptional alterations suggestive of epithelial-mesenchymal transition in isolated premalignant lung tumour cells ex vivo, and are required for the maintenance of early-stage lung tumours in vivo. Furthermore, we have found that IMC recruitment to the microenvironment is restrained by the cholesterol-binding protein, Niemann-Pick type C2 (NPC2). Studies on isolated cells ex vivo confirm that NPC2 is secreted from tumour cells and is taken up by IMCs wherein it suppresses secretion of the CCR1 ligand CC chemokine 6 (CCL6), at least in part by facilitating its lysosomal degradation. Together, these findings show that NPC2 secreted by premalignant lung tumours suppresses IMC recruitment to the microenvironment in a paracrine manner, thus identifying a novel target for the development of chemopreventive strategies in lung cancer. PMID:26183450

  16. Inverter testing at Sandia National Laboratories

    SciTech Connect

    Ginn, J.W.; Bonn, R.H.; Sittler, G.

    1997-04-01

    Inverters are key building blocks of photovoltaic (PV) systems that produce ac power. The balance of systems (BOS) portion of a PV system can account for up to 50% of the system cost, and its reliable operation is essential for a successful PV system. As part of its BOS program, Sandia National Laboratories (SNL) maintains a laboratory wherein accurate electrical measurements of power systems can be made under a variety of conditions. This paper outlines the work that is done in that laboratory.

  17. Rhenium Disulfide Depletion-Load Inverter

    NASA Astrophysics Data System (ADS)

    McClellan, Connor; Corbet, Chris; Rai, Amritesh; Movva, Hema C. P.; Tutuc, Emanuel; Banerjee, Sanjay K.

    2015-03-01

    Many semiconducting Transition Metal Dichalcogenide (TMD) materials have been effectively used to create Field-Effect Transistor (FET) devices but have yet to be used in logic designs. We constructed a depletion-load voltage inverter using ultrathin layers of Rhenium Disulfide (ReS2) as the semiconducting channel. This ReS2 inverter was fabricated on a single micromechanically-exfoliated flake of ReS2. Electron beam lithography and physical vapor deposition were used to construct Cr/Au electrical contacts, an Alumina top-gate dielectric, and metal top-gate electrodes. By using both low (Aluminum) and high (Palladium) work-function metals as two separate top-gates on a single ReS2 flake, we create a dual-gated depletion mode (D-mode) and enhancement mode (E-mode) FETs in series. Both FETs displayed current saturation in the output characteristics as a result of the FET ``pinch-off'' mechanism and On/Off current ratios of 105. Field-effect mobilities of 23 and 17 cm2V-1s-1 and subthreshold swings of 97 and 551 mV/decade were calculated for the E-mode and D-mode FETs, respectively. With a supply voltage of 1V, at low/negative input voltages the inverter output was at a high logic state of 900 mV. Conversely with high/positive input voltages, the inverter output was at a low logic state of 500 mV. The inversion of the input signal demonstrates the potential for using ReS2 in future integrated circuit designs and the versatility of depletion-load logic devices for TMD research. NRI SWAN Center and ARL STTR Program.

  18. Inverted colloidal quantum dot solar cells.

    PubMed

    Kim, Gi-Hwan; Walker, Bright; Kim, Hak-Beom; Kim, Jin Young; Sargent, Edward H; Park, Jongnam; Kim, Jin Young

    2014-05-28

    An inverted architecture of quantum dot solar cells is demonstrated by introducing a novel ZnO method on top of the PbS CQD film. Improvements in device characteristics stem from constructive optical interference from the ZnO layer that enhances absorption in the PbS CQD layer. Outstanding diode characteristics arising from a superior PbS/ZnO junction provide a further electronic advantage. PMID:24677118

  19. Sizing SiC Storage Inverters for Fast Grid Frequency Support

    SciTech Connect

    Hoke, Anderson; Bennion, Kevin; Gevorgian, Vahan; Chakraborty, Sudipta; Muljadi, Eduard

    2015-11-02

    As wind and solar displace synchronous generators whose inertia stabilizes the AC grid frequency on fast time scales, it has been proposed to use energy storage systems (ESSs) to mitigate frequency transient events. Such events require a rapid surge of power from the ESS, but they occur only rarely. The high temperature tolerance of SiC MOSFETs and diodes presents an opportunity for innovative ESS inverter designs. Herein we investigate a SiC ESS inverter design such that the SiC device ratings are obeyed during mild frequency events but are exceeded during rare, major events, for a potentially more economical inverter design. In support of this proposal we present: 1. An analysis of four years of grid frequency events in the U.S. Western Interconnection. 2. A switch-level ESS inverter simulation using SiC devices with detailed loss estimates. 3. Thermal analysis of the SiC power modules during a worst-case frequency event, showing that the modules can likely withstand the brief overcurrent. This analysis supports the conclusion that it may be advantageous for economical designs (acknowledging the increased risks) to undersize the SiC switches when designing inverters to perform active power control for grid frequency support. Such a strategy may result in SiC-based designs being more competitive with less costly silicon IGBT-based designs.

  20. FET commutated current-FED inverter

    NASA Technical Reports Server (NTRS)

    Rippel, Wally E. (Inventor); Edwards, Dean B. (Inventor)

    1983-01-01

    A shunt switch comprised of a field-effect transistor (Q.sub.1) is employed to commutate a current-fed inverter (10) using thyristors (SCR1, SCR2) or bijunction transistors (Q.sub.2, Q.sub.3) in a full bridge (1, 2, 3, 4) or half bridge (5, 6) and transformer (T.sub.1) configuration. In the case of thyristors, a tapped inverter (12) is employed to couple the inverter to a dc source to back bias the thyristors during commutation. Alternatively, a commutation power supply (20) may be employed for that purpse. Diodes (D.sub.1, D.sub.2) in series with some voltage dropping element (resistor R.sub.12 or resistors R.sub.1, R.sub.2 or Zener diodes D.sub.4, D.sub.5) are connected in parallel with the thyristors in the half bridge and transformer configuration to assure sharing the back bias voltage. A clamp circuit comprised of a winding (18) negatively coupled to the inductor and a diode (D.sub.3) return stored energy from the inductor to the power supply for efficient operation with buck or boost mode.

  1. An integrated technique for eliminating harmonics of multilevel inverter with unequal DC sources

    NASA Astrophysics Data System (ADS)

    Malarvizhi, M.; Gnanambal, I.

    2015-02-01

    For improving the alteration performance of multilevel inverter, selective harmonics elimination methods play a significant role. In this document, an incorporated method is suggested for removing the harmonics of multilevel inverter with uneven DC sources. The suggested incorporated method is the mixture of fuzzy logic intelligent system and particle swarm optimisation (PSO) algorithm. For generating the training information set in terms of switching angle, Fuzzy is one of the synthetic intelligent methods which apply harmonic voltage and harmonic distortion. PSO is one of the swarm intelligence-based optimisation algorithms which is employed for choosing optimal switching angle from the training data set. The suggested hybrid method is executed in MATLAB/Simulink platform. At dissimilar unequal input voltage levels, the performance of the suggested method is checked by cascade H-bridge multilevel inverter. The production of the suggested method is compared with the theoretical effects.

  2. A Novel Inductor-less DC-AC Cascaded H-bridge Multilevel Boost Inverter for Electric/Hybrid Electric Vehicle Applications

    SciTech Connect

    Du, Zhong; Ozpineci, Burak; Tolbert, Leon M; Chiasson, John N

    2007-01-01

    This paper presents an inductorless cascaded H- bridge multilevel boost inverter for EV and HEV applications. Currently available power inverter systems for HEVs use a DC- DC boost converter to boost the battery voltage for a traditional 3-phase inverter. The present HEV traction drive inverters have low power density, are expensive, and have low efficiency because they need a bulky inductor. An inductorless cascaded H-bridge multilevel boost inverter for EV and HEV applications is proposed in this paper. Traditionally, each H-bridge needs a DC power supply. The proposed inductorless cascaded H-bridge multilevel boost inverter uses a standard 3-leg inverter (one leg for each phase) and an H-bridge in series with each inverter leg which uses a capacitor as the DC power source. Fundamental switching scheme is used to do modulation control and to produce a 5-level phase voltage. Experiments show that the proposed inductorless DC-AC cascaded H-bridge multilevel boost inverter can output a boosted AC voltage.

  3. High Power Factor Control Regulating Inverter Output Power in IPM Motor Driven by Inverter System without Electrolytic Capacitor

    NASA Astrophysics Data System (ADS)

    Inazuma, Kazuya; Ohishi, Kiyoshi; Haga, Hitoshi; Sazawa, Mataki; Kondo, Seiji

    This paper presents a new high power factor control method for a single-to-three-phase power converter without an electrolytic capacitor. The circuit used in the method consists of a single-phase rectifier, a small film capacitor at DC-link, a voltage-source three-phase inverter, and an IPM motor. The inverter regulates both the velocity of the IPM motor and input current waveform. In order to obtain a power factor of unity, we propose a new control method that regulates the inverter output power. The inverter output power controller is placed between the speed controller and the q-axis current controller. The inverter power is regulated by a PI and repetitive controller. When repetitive control is applied to the inverter power controller, the phase delay of the inverter power controller is quite small. The superior performance of the proposed method is demonstrated by experimental results.

  4. Inverted (hobnail) high-grade prostatic intraepithelial neoplasia and invasive inverted pattern

    PubMed Central

    ÖZNUR, MELTEM; KOCA, SEVIM BAYKAL; YILDIZ, PELIN; BAHADIR, BURAK; BEHZATOĞLU, KEMAL

    2015-01-01

    High-grade prostatic intraepithelial neoplasia (HGPIN) is considered to be an important precursor for prostatic adenocarcinoma. The present study aimed to investigate the histological features of the uncommon inverted (hobnail) pattern of HGPIN in transrectal ultrasonographic (TRUS) prostatic needle biopsies from 13 cases. These 13 diagnosed cases of inverted HGPIN were identified out of a total of 2,034 TRUS biopsies (0.63%), obtained from patients suspected to have prostate cancer. The hobnail pattern is comprised of secretory cell nuclei, which are histologically localized at the luminal surface of the prostate gland, rather than the periphery, and exhibit reverse polarity. Histological examinations were performed and the results demonstrated that 5 of the 13 cases exhibited pure inverted histology, while HGPIN was observed to be histologically associated with other patterns in the remaining 8 patients. In addition, an association with adenocarcinoma was identified in 7 of the 13 cases. All 7 carcinomas accompanied by inverted HGPIN were conventional acinar adenocarcinoma cases; of note, for these 7 cases, the Gleason score was 7 for each. One acinar adenocarcinoma case accompanying inverted HGPIN demonstrated hobnail characteristics in large areas of the invasive component. It was observed that nuclei were proliferated in the invasive cribriform glands, which was comparable to that of inverted HGPIN, and were located on the cytoplasmic luminal surface; a similar morphology was also observed in individual glands. In conclusion, the results of the present study suggested that the hobnail HGPIN pattern may be of diagnostic importance due to its high association with adenocarcinoma and the high Gleason scores in the accompanying carcinomas. PMID:26622858

  5. Influence of the inverter characteristics on the iron losses in PWM inverter fed induction motors

    SciTech Connect

    Boglietti, A.; Ferraris, P.; Lazzari, M.; Pastorelli, M.

    1995-12-31

    In this paper the authors deal with the effects of the inverter characteristics on the iron losses increment in induction motors fed by PWM controlled converters. Laboratory tests based on no-load input power measurement were carried out and in order to avoid the influence of mechanical losses and rotor copper losses, difficult to be measured or computed, a special test bench with an unconventional test device was employed. In particular the influence of the following inverter parameters are considered: modulation index; modulation waveform; switching frequency. Complete experimental results are presented and discussed.

  6. Advanced Photovoltaic Inverter Functionality using 500 kW Power Hardware-in-Loop Complete System Laboratory Testing: Preprint

    SciTech Connect

    Mather, B. A.; Kromer, M. A.; Casey, L.

    2013-01-01

    With the increasing penetration of distribution connected photovoltaic (PV) systems, more and more PV developers and utilities are interested in easing future PV interconnection concerns by mitigating some of the impacts of PV integration using advanced PV inverter controls and functions. This paper describes the testing of a 500 kW PV inverter using Power Hardware-in-Loop (PHIL) testing techniques. The test setup is described and the results from testing the inverter in advanced functionality modes, not commonly used in currently interconnected PV systems, are presented. PV inverter operation under PHIL evaluation that emulated both the DC PV array connection and the AC distribution level grid connection are shown for constant power factor (PF) and constant reactive power (VAr) control modes. The evaluation of these modes was completed under varying degrees of modeled PV variability.

  7. Dynamics of quiet human stance: computer simulations of a triple inverted pendulum model.

    PubMed

    Günther, Michael; Wagner, Heiko

    2016-01-01

    For decades, the biomechanical description of quiet human stance has been dominated by the single inverted pendulum (SIP) paradigm. However, in the past few years, the SIP model family has been falsified as an explanatory approach. Double inverted pendulum models have recently proven to be inappropriate. Human topology with three major leg joints suggests in a natural way to examine triple inverted pendulum (TIP) models as an appropriate approach. In this study, we focused on formulating a TIP model that can synthesise stable balancing attractors based on minimalistic sensor information and actuation complexity. The simulated TIP oscillation amplitudes are realistic in vertical direction. Along with the horizontal ankle, knee and hip positions, though, all simulated joint angle amplitudes still exceed the measured ones about threefold. It is likely that they could be eventually brought down to the physiological range by using more sensor information. The TIP systems' eigenfrequency spectra come out as another major result. The eigenfrequencies spread across about 0.1 Hz...20 Hz. Our main result is that joint stiffnesses can be reduced even below statically required values by using an active hip torque balancing strategy. When reducing mono- and bi-articular stiffnesses further down to levels threatening dynamic stability, the spectra indicate a change from torus-like (stable) to strange (chaotic) attractors. Spectra of measured ground reaction forces appear to be strange-attractor-like. We would conclude that TIP models are a suitable starting point to examine more deeply the dynamic character of and the essential structural properties behind quiet human stance. Abbreviations and technical terms Inverted pendulum body exposed to gravity and pivoting in a joint around position of unstable equilibrium (operating point) SIP single inverted pendulum: one rigid body pivoting around fixation to the ground (external joint) DIP double inverted pendulum: two bodies

  8. Semi-transparent inverted organic solar cells

    NASA Astrophysics Data System (ADS)

    Schmidt, H.; Winkler, T.; Tilgner, M.; Flügge, H.; Schmale, S.; Bülow, T.; Meyer, J.; Johannes, H.-H.; Riedl, T.; Kowalsky, W.

    2009-08-01

    We will present efficient semi-transparent bulk-heterojunction [regioregular of poly(3-hexylthiophene): (6,6)-phenyl C61 butyric acid methyl ester] solar cells with an inverted device architecture. Highly transparent ZnO and TiO2 films prepared by Atomic Layer Deposition are used as cathode interlayers on top of ITO. The topanode consists of a RF-sputtered ITO layer. To avoid damage due to the plasma deposition of this layer, a sputtering buffer layer of MoO3 is used as protection. This concept allows for devices with a transmissivity higher than 60 % for wavelengths 650 nm. The thickness of the MoO3 buffer has been varied in order to study its effect on the electrical properties of the solar cell and its ability to prevent possible damage to the organic active layers upon ITO deposition. Without this buffer or for thin buffers it has been found that device performance is very poor concerning the leakage current, the fill factor, the short circuit current and the power conversion efficiencies. As a reference inverted solar cells with a metal electrode (Al) instead of the ITO-top contact are used. The variation between the PCE of top versus conventional illumination of the semi-transparent cells was also examined and will be interpreted in view of the results of the optical simulation of the dielectric device stack with and without reflection top electrode. Power conversion efficiencies of 2-3 % for the opaque inverted solar cells and 1.5-2.5 % for the semi-transparent devices were obtained under an AM1.5G illumination.

  9. Volunteer Losing Balance Wearing Inverted Glasses

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Brad McLain for the Space Biology Museum Network puts a volunteer back on balance as he tries to adjust to a world inverted by a special pair of glasses. This helps illustrate how dependent the human vestibular system is on visual cues. A volunteer is The activity was part of the Space Research and You education event held by NASA's Office of Biological and Physical Research on June 25, 2002, in Arlington, VA, to highlight the research that will be conducted on STS-107.

  10. Apollo 14 inverted pigeonites - Possible samples of lunar plutonic rocks.

    NASA Technical Reports Server (NTRS)

    Papike, J. J.; Bence, A. E.

    1972-01-01

    Analysis of 'inverted pigeonites' found in Apollo 14 samples 14082 and 14083 (a polymict breccia, the 'white rock') by a combination of optical, electron probe, and single-crystal X-ray diffraction techniques. These 'inverted pigeonites' are regarded as samples of plutonic rocks that have been blasted out of the Imbrium Basin. It is also concluded that lunar pigeonites will invert to orthopyroxenes, given sufficiently slow cooling histories even in very anhydrous environments.