NEMO Inhibits Programmed Necrosis in an NFκB-Independent Manner by Restraining RIP1

PubMed Central

Legarda, Diana; Ting, Adrian T.

2012-01-01

TNF can trigger two opposing responses: cell survival and cell death. TNFR1 activates caspases that orchestrate apoptosis but some cell types switch to a necrotic death when treated with caspase inhibitors. Several genes that are required to orchestrate cell death by programmed necrosis have been identified, such as the kinase RIP1, but very little is known about the inhibitory signals that keep this necrotic cell death pathway in check. We demonstrate that T cells lacking the regulatory subunit of IKK, NFκB essential modifier (NEMO), are hypersensitive to programmed necrosis when stimulated with TNF in the presence of caspase inhibitors. Surprisingly, this pro-survival activity of NEMO is independent of NFκB-mediated gene transcription. Instead, NEMO inhibits necrosis by binding to ubiquitinated RIP1 to restrain RIP1 from engaging the necrotic death pathway. In the absence of NEMO, or if ubiquitination of RIP1 is blocked, necrosis ensues when caspases are blocked. These results indicate that recruitment of NEMO to ubiquitinated RIP1 is a key step in the TNFR1 signaling pathway that determines whether RIP1 triggers a necrotic death response. PMID:22848449

Inhibition of the NEMO/IKKβ association complex formation, a novel mechanism associated with the NF-κB activation suppression by Withania somnifera's key metabolite withaferin A.

PubMed

Grover, Abhinav; Shandilya, Ashutosh; Punetha, Ankita; Bisaria, Virendra S; Sundar, Durai

2010-12-02

Nuclear Factor kappa B (NF-κB) is a transcription factor involved in the regulation of cell signaling responses and is a key regulator of cellular processes involved in the immune response, differentiation, cell proliferation, and apoptosis. The constitutive activation of NF-κB contributes to multiple cellular outcomes and pathophysiological conditions such as rheumatoid arthritis, asthma, inflammatory bowel disease, AIDS and cancer. Thus there lies a huge therapeutic potential beneath inhibition of NF-κB signalling pathway for reducing these chronic ailments. Withania somnifera, a reputed herb in ayurvedic medicine, comprises a large number of steroidal lactones known as withanolides which show plethora of pharmacological activities like anti- inflammatory, antitumor, antibacterial, antioxidant, anticonvulsive, and immunosuppressive. Though a few studies have been reported depicting the effect of WA (withaferin A) on suppression of NF-κB activation, the mechanism behind this is still eluding the researchers. The study conducted here is an attempt to explore NF-κB signalling pathway modulating capability of Withania somnifera's major constituent WA and to elucidate its possible mode of action using molecular docking and molecular dynamics simulations studies. Formation of active IKK (IκB kinase) complex comprising NEMO (NF-κB Essential Modulator) and IKKβ subunits is one of the essential steps for NF-κB signalling pathway, non-assembly of which can lead to prevention of the above mentioned vulnerable disorders. As observed from our semi-flexible docking analysis, WA forms strong intermolecular interactions with the NEMO chains thus building steric as well as thermodynamic barriers to the incoming IKKβ subunits, which in turn pave way to naive complex formation capability of NEMO with IKKβ. Docking of WA into active NEMO/IKKβ complex using flexible docking in which key residues of the complex were kept flexible also suggest the disruption of the active

Nor-ursodeoxycholic acid reverses hepatocyte-specific nemo-dependent steatohepatitis.

PubMed

Beraza, Naiara; Ofner-Ziegenfuss, Lisa; Ehedego, Haksier; Boekschoten, Mark; Bischoff, Stephan C; Mueller, Michael; Trauner, Michael; Trautwein, Christian

2011-03-01

Hepatocyte-specific NEMO/NF-κB deleted mice (NEMO(Δhepa)) develop spontaneous non-alcoholic steatohepatitis (NASH). Free fatty acids and bile acids promote DR5 expression. TRAIL/NK cell-mediated activation of TRAIL-R2/DR5 plays an important role during acute injury in NEMO(Δhepa) mice. To inhibit the progression of NASH in the absence of hepatocyte-NEMO/NF-kB signaling. NEMOf/f and NEMO(Δhepa) mice were fed with a low-fat diet, and with two anticholestatic diets; UDCA and NorUDCA. The impact of these treatments on the progression of NASH was evaluated. We show that high expression of DR5 in livers from NEMO(Δhepa) mice is accompanied by an abundant presence of bile acids (BAs), misregulation of BA transporters and significant alteration of lipid metabolism-related genes. Additionally, mice lacking NEMO in hepatocytes spontaneously showed ductular response at young age. Unexpectedly, feeding of NEMO(Δhepa) mice with low-fat diet failed to improve chronic liver injury. Conversely, anti-cholestatic treatment with nor-ursodeoxycholic acid (NorUDCA), but not with ursodeoxycholic acid (UDCA), led to a significant attenuation of liver damage in NEMO(Δhepa) mice. The strong therapeutic effect of NorUDCA relied on a significant downregulation of LXR-dependent lipogenesis and the normalisation of BA metabolism through mechanisms involving cross-talk between Cyp7a1 and SHP. This was associated with the significant improvement of liver histology, NEMO(Δhepa)/NorUDCA-treated mice showed lower apoptosis and reduced CyclinD1 expression, indicating attenuation of the compensatory proliferative response to hepatocellular damage. Finally, fibrosis and ductular reaction markers were significantly reduced in NorUDCA-treated NEMO(Δhepa) mice. Overall, our work demonstrates the contribution of bile acids metabolism to the progression of NASH in the absence of hepatocyte-NF-kB through mechanisms involving DR5-apoptosis, inflammation and fibrosis. Our work suggests a potential

Inhibition of Canonical NF-κB Signaling by a Small Molecule Targeting NEMO-Ubiquitin Interaction

PubMed Central

Vincendeau, Michelle; Hadian, Kamyar; Messias, Ana C.; Brenke, Jara K.; Halander, Jenny; Griesbach, Richard; Greczmiel, Ute; Bertossi, Arianna; Stehle, Ralf; Nagel, Daniel; Demski, Katrin; Velvarska, Hana; Niessing, Dierk; Geerlof, Arie; Sattler, Michael; Krappmann, Daniel

2016-01-01

The IκB kinase (IKK) complex acts as the gatekeeper of canonical NF-κB signaling, thereby regulating immunity, inflammation and cancer. It consists of the catalytic subunits IKKα and IKKβ and the regulatory subunit NEMO/IKKγ. Here, we show that the ubiquitin binding domain (UBAN) in NEMO is essential for IKK/NF-κB activation in response to TNFα, but not IL-1β stimulation. By screening a natural compound library we identified an anthraquinone derivative that acts as an inhibitor of NEMO-ubiquitin binding (iNUB). Using biochemical and NMR experiments we demonstrate that iNUB binds to NEMOUBAN and competes for interaction with methionine-1-linked linear ubiquitin chains. iNUB inhibited NF-κB activation upon UBAN-dependent TNFα and TCR/CD28, but not UBAN-independent IL-1β stimulation. Moreover, iNUB was selectively killing lymphoma cells that are addicted to chronic B-cell receptor triggered IKK/NF-κB activation. Thus, iNUB disrupts the NEMO-ubiquitin protein-protein interaction interface and thereby inhibits physiological and pathological NF-κB signaling. PMID:26740240

Essentially semismall Quasi-Dedekind module relative to a module

NASA Astrophysics Data System (ADS)

Hussain, Mukdad Q.

2018-05-01

Let R be associative ring with identity and M be a unitary R-module. In this paper study the direct summand of essentially semismall quasi-Dedekind module and prove that the direct sum of essentially semismall quasi-Dedekind modules need not be essentially semismall quasi-Dedekind and give the definition of essentially semismall quasi-Dedekind relative to a module with some examples, also give some of their basic properties and some examples that illustrate these properties.

NEMO: Status of the Project

NASA Astrophysics Data System (ADS)

Migneco, E.; Aiello, S.; Amato, E.; Ambriola, M.; Ameli, F.; Andronico, G.; Anghinolfi, M.; Battaglieri, M.; Bellotti, R.; Bersani, A.; Boldrin, A.; Bonori, M.; Cafagna, F.; Capone, A.; Caponnetto, L.; Chiarusi, T.; Circella, M.; Cocimano, R.; Coniglione, R.; Cordelli, M.; Costa, M.; Cuneo, S.; D'Amico, A.; D'Amico, V.; De Marzo, C.; De Vita, R.; Distefano, C.; Gabrielli, A.; Gandolfi, E.; Grimaldi, A.; Habel, R.; Italiano, A.; Leonardi, M.; Lo Nigro, L.; Lo Presti, D.; Margiotta, A.; Martini, A.; Masetti, M.; Masullo, R.; Montaruli, T.; Mosetti, R.; Musumeci, M.; Nicolau, C. A.; Occhipinti, R.; Papaleo, R.; Petta, C.; Piattelli, P.; Raia, G.; Randazzo, N.; Reito, S.; Ricco, G.; Riccobene, G.; Ripani, M.; Romita, M.; Rovelli, A.; Ruppi, M.; Russo, G. V.; Russo, M.; Sapienza, P.; Schuller, J. P.; Sedita, M.; Sokalski, I.; Spurio, M.; Taiuti, M.; Trasatti, L.; Ursella, L.; Valente, V.; Vicini, P.; Zanarini, G.

2004-11-01

The activities towards the realisation of a km3 Cherenkov neutrino detector, carried out by the NEMO Collaboration are described. Long term exploration of a 3500 m deep site close to the Sicilian coast has shown that it is optimal for the installation of the detector. A complete feasibility study, that has considered all the components of the detector as well as its deployment, has been carried out demonstrating that technological solutions exist for the realization of an underwater km3 detector. The realization of a technological demonstrator (the NEMO Phase 1 project) is under way.

Death receptor-independent FADD signalling triggers hepatitis and hepatocellular carcinoma in mice with liver parenchymal cell-specific NEMO knockout.

PubMed

Ehlken, H; Krishna-Subramanian, S; Ochoa-Callejero, L; Kondylis, V; Nadi, N E; Straub, B K; Schirmacher, P; Walczak, H; Kollias, G; Pasparakis, M

2014-11-01

Hepatocellular carcinoma (HCC) usually develops in the context of chronic hepatitis triggered by viruses or toxic substances causing hepatocyte death, inflammation and compensatory proliferation of liver cells. Death receptors of the TNFR superfamily regulate cell death and inflammation and are implicated in liver disease and cancer. Liver parenchymal cell-specific ablation of NEMO/IKKγ, a subunit of the IκB kinase (IKK) complex that is essential for the activation of canonical NF-κB signalling, sensitized hepatocytes to apoptosis and caused the spontaneous development of chronic hepatitis and HCC in mice. Here we show that hepatitis and HCC development in NEMO(LPC-KO) mice is triggered by death receptor-independent FADD-mediated hepatocyte apoptosis. TNF deficiency in all cells or conditional LPC-specific ablation of TNFR1, Fas or TRAIL-R did not prevent hepatocyte apoptosis, hepatitis and HCC development in NEMO(LPC-KO) mice. To address potential functional redundancies between death receptors we generated and analysed NEMO(LPC-KO) mice with combined LPC-specific deficiency of TNFR1, Fas and TRAIL-R and found that also simultaneous lack of all three death receptors did not prevent hepatocyte apoptosis, chronic hepatitis and HCC development. However, LPC-specific combined deficiency in TNFR1, Fas and TRAIL-R protected the NEMO-deficient liver from LPS-induced liver failure, showing that different mechanisms trigger spontaneous and LPS-induced hepatocyte apoptosis in NEMO(LPC-KO) mice. In addition, NK cell depletion did not prevent liver damage and hepatitis. Moreover, NEMO(LPC-KO) mice crossed into a RAG-1-deficient genetic background-developed hepatitis and HCC. Collectively, these results show that the spontaneous development of hepatocyte apoptosis, chronic hepatitis and HCC in NEMO(LPC-KO) mice occurs independently of death receptor signalling, NK cells and B and T lymphocytes, arguing against an immunological trigger as the critical stimulus driving

PORFIDO on the NEMO Phase 2 tower

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

Ciaffoni, Orlando; Cordelli, Marco; Habel, Roberto

We have designed and built an underwater measurement system, PORFIDO (Physical Oceanography by RFID Outreach) to gather oceanographic data from the Optical Modules of a neutrino telescope with a minimum of disturbance to the main installation. PORFIDO is composed of a sensor glued to the outside of an Optical Module, in contact with seawater, and of a reader placed inside the sphere, facing the sensor. Data are transmitted to the reader through the glass by RFID and to shore in real time for periods of years. The sensor gathers power from the radio frequency, thus eliminating the need for batteriesmore » or connectors through the glass. We have deployed four PORFIDO probes measuring temperatures with the NEMO-KM3Net-Italy Phase 2 tower in april 2013. The four probes are operative and are transmitting temperature data from 3500 m depth.« less

Data transmission and acquisition in NEMO

NASA Astrophysics Data System (ADS)

Bunkheila, G.

2006-11-01

A comprehensive system for data transmission and acquisition has been developed for an "à la NEMO" underwater neutrino telescope based on Čerenkov light detection using photomultipliers (PMTs) as sensors. Signals generated by each sensor are triggered, sampled and tagged by an electronics board, called Front End Module (FEM). Data streams from up to eight FEMs located on one tower floor are collected by a concentration board called Floor Control Module (FCM) and sent to a twin FCM board—located at the onshore station and plugged into an interface machine (FCM Interface, or FCMI) via a PCI bus—through a DWDM-compliant optical fiber and using a self-synchronous serial protocol. All sensor data reach the onshore lab through FCMI where they are made available to subsequent elaboration processes, such as time-wise alignment and muon track event-triggering. To meet requirements of the latter, onshore data unpacking is carried out with respect to their topological origin. The system promised, and keeps on showing, very light charges on power consumption and infrastructure complexity, while having recently proved to behave at high performance levels in its optical part.

GeNemo: a search engine for web-based functional genomic data.

PubMed

Zhang, Yongqing; Cao, Xiaoyi; Zhong, Sheng

2016-07-08

A set of new data types emerged from functional genomic assays, including ChIP-seq, DNase-seq, FAIRE-seq and others. The results are typically stored as genome-wide intensities (WIG/bigWig files) or functional genomic regions (peak/BED files). These data types present new challenges to big data science. Here, we present GeNemo, a web-based search engine for functional genomic data. GeNemo searches user-input data against online functional genomic datasets, including the entire collection of ENCODE and mouse ENCODE datasets. Unlike text-based search engines, GeNemo's searches are based on pattern matching of functional genomic regions. This distinguishes GeNemo from text or DNA sequence searches. The user can input any complete or partial functional genomic dataset, for example, a binding intensity file (bigWig) or a peak file. GeNemo reports any genomic regions, ranging from hundred bases to hundred thousand bases, from any of the online ENCODE datasets that share similar functional (binding, modification, accessibility) patterns. This is enabled by a Markov Chain Monte Carlo-based maximization process, executed on up to 24 parallel computing threads. By clicking on a search result, the user can visually compare her/his data with the found datasets and navigate the identified genomic regions. GeNemo is available at www.genemo.org. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Fibroblast growth factor homologous factor 1 interacts with NEMO to regulate NF-κB signaling in neurons.

PubMed

König, Hans-Georg; Fenner, Beau J; Byrne, Jennifer C; Schwamborn, Robert F; Bernas, Tytus; Jefferies, Caroline A; Prehn, Jochen H M

2012-12-15

Neuronal survival and plasticity critically depend on constitutive activity of the transcription factor nuclear factor-κB (NF-κB). We here describe a role for a small intracellular fibroblast growth factor homologue, the fibroblast growth factor homologous factor 1 (FHF1/FGF12), in the regulation of NF-κB activity in mature neurons. FHFs have previously been described to control neuronal excitability, and mutations in FHF isoforms give rise to a form of progressive spinocerebellar ataxia. Using a protein-array approach, we identified FHF1b as a novel interactor of the canonical NF-κB modulator IKKγ/NEMO. Co-immunoprecipitation, pull-down and GAL4-reporter experiments, as well as proximity ligation assays, confirmed the interaction of FHF1 and NEMO and demonstrated that a major site of interaction occurred within the axon initial segment. Fhf1 gene silencing strongly activated neuronal NF-κB activity and increased neurite lengths, branching patterns and spine counts in mature cortical neurons. The effects of FHF1 on neuronal NF-κB activity and morphology required the presence of NEMO. Our results imply that FHF1 negatively regulates the constitutive NF-κB activity in neurons.

Nemo: an evolutionary and population genetics programming framework.

PubMed

Guillaume, Frédéric; Rougemont, Jacques

2006-10-15

Nemo is an individual-based, genetically explicit and stochastic population computer program for the simulation of population genetics and life-history trait evolution in a metapopulation context. It comes as both a C++ programming framework and an executable program file. Its object-oriented programming design gives it the flexibility and extensibility needed to implement a large variety of forward-time evolutionary models. It provides developers with abstract models allowing them to implement their own life-history traits and life-cycle events. Nemo offers a large panel of population models, from the Island model to lattice models with demographic or environmental stochasticity and a variety of already implemented traits (deleterious mutations, neutral markers and more), life-cycle events (mating, dispersal, aging, selection, etc.) and output operators for saving data and statistics. It runs on all major computer platforms including parallel computing environments. The source code, binaries and documentation are available under the GNU General Public License at http://nemo2.sourceforge.net.

Evaluation of QoS supported in Network Mobility NEMO environments

NASA Astrophysics Data System (ADS)

Hussien, L. F.; Abdalla, A. H.; Habaebi, M. H.; Khalifa, O. O.; Hassan, W. H.

2013-12-01

Network mobility basic support (NEMO BS) protocol is an entire network, roaming as a unit which changes its point of attachment to the Internet and consequently its reachability in the network topology. NEMO BS doesn't provide QoS guarantees to its users same as traditional Internet IP and Mobile IPv6 as well. Typically, all the users will have same level of services without considering about their application requirements. This poses a problem to real-time applications that required QoS guarantees. To gain more effective control of the network, incorporated QoS is needed. Within QoS-enabled network the traffic flow can be distributed to various priorities. Also, the network bandwidth and resources can be allocated to different applications and users. Internet Engineering Task Force (IETF) working group has proposed several QoS solutions for static network such as IntServ, DiffServ and MPLS. These QoS solutions are designed in the context of a static environment (i.e. fixed hosts and networks). However, they are not fully adapted to mobile environments. They essentially demands to be extended and adjusted to meet up various challenges involved in mobile environments. With existing QoS mechanisms many proposals have been developed to provide QoS for individual mobile nodes (i.e. host mobility). In contrary, research based on the movement of the whole mobile network in IPv6 is still undertaking by the IETF working groups (i.e. network mobility). Few researches have been done in the area of providing QoS for roaming networks. Therefore, this paper aims to review and investigate (previous /and current) related works that have been developed to provide QoS in mobile network. Consequently, a new proposed scheme will be introduced to enhance QoS within NEMO environment, achieving by which seamless mobility to users of mobile network node (MNN).

SN-1 and NEMO: the Italian cabled observatories

NASA Astrophysics Data System (ADS)

Favali, P.; Beranzoli, L.; Calore, D.; D'Anna, G.; Gasparoni, F.; NEMO Collaboration Team

2003-04-01

A fruitful synergy between Geophysics, Environmental Sciences, Nuclear Physics and Marine Technology has started through ongoing projects within different Italian research frameworks. The Neutrino Mediterranean Observatory (NEMO) project, funded by INFN, aims at the realization of a deep-sea experiment for the detection of cosmic neutrinos using an array of towers equipped by photosensors. To test the technological solutions proposed for the realization of the project, the Laboratiori Nazionali del Sud have set up an underwater Test Site off-shore Catania. A 25 km long submarine electro-optical cable was deployed in September 2001, in order to supply power from land and receive data from the underwater site located at a depth of 2000 m. A shore station has also been realize inside the Catania port area. In October 2001, Submarine Network-1 (SN-1), the first Italian deep-sea multidisciplinary observatory for geophysical and environmental monitoring was deployed at a depth of 2105 m, in the area of the Ibleo-maltese escarpment, in proximity of the marine tail of the NEMO cable. SN-1, funded by the Italian Gruppo Nazionale di Difesa dai Terremoti and coordinated by INGV, is presently operating in local mode storing measurements on hard disks and is powered by lithium batteries with an autonomy of approximately 200 days. In the view of mutual assistance, the coordinator institutions of NEMO and SN-1 have agreed that part of the optic fibres and power lines of the NEMO-1 underwater cable be made available to power SN-1 from land and to transfer in real time the signals acquired by the geophysical and environmental sensor packages of SN-1. On this latter's side, time series of environmental parameters useful for the analysis and interpretation of NEMO-1 detections will be available. A description of the two projects and of the 'state of the art' will be given and the benefits of the development of a submarine Italian prone site will be pointed out.

Modelling turbulent vertical mixing sensitivity using a 1-D version of NEMO

NASA Astrophysics Data System (ADS)

Reffray, G.; Bourdalle-Badie, R.; Calone, C.

2014-08-01

Through two numerical experiments, a 1-D vertical model called NEMO1D was used to investigate physical and numerical turbulent-mixing behaviour. The results show that all the turbulent closures tested (k + l from Blanke and Delecluse, 1993 and two equation models: Generic Lengh Scale closures from Umlauf and Burchard, 2003) are able to correctly reproduce the classical test of Kato and Phillips (1969) under favourable numerical conditions while some solutions may diverge depending on the degradation of the spatial and time discretization. The performances of turbulence models were then compared with data measured over a one-year period (mid-2010 to mid-2011) at the PAPA station, located in the North Pacific Ocean. The modelled temperature and salinity were in good agreement with the observations, with a maximum temperature error between -2 and 2 °C during the stratified period (June to October). However the results also depend on the numerical conditions. The vertical RMSE varied, for different turbulent closures, from 0.1 to 0.3 °C during the stratified period and from 0.03 to 0.15 °C during the homogeneous period. This 1-D configuration at the PAPA station (called PAPA1D) is now available in NEMO as a reference configuration including the input files and atmospheric forcing set described in this paper. Thus, all the results described can be recovered by downloading and launching PAPA1D. The configuration is described on the NEMO site (nemo-ocean.eu/Using-NEMO/Configurations/C1D_PAPA">http://www.nemo-ocean.eu/Using-NEMO/Configurations/C1D_PAPA). This package is a good starting point for further investigation of vertical processes.

Modelling turbulent vertical mixing sensitivity using a 1-D version of NEMO

NASA Astrophysics Data System (ADS)

Reffray, G.; Bourdalle-Badie, R.; Calone, C.

2015-01-01

Through two numerical experiments, a 1-D vertical model called NEMO1D was used to investigate physical and numerical turbulent-mixing behaviour. The results show that all the turbulent closures tested (k+l from Blanke and Delecluse, 1993, and two equation models: generic length scale closures from Umlauf and Burchard, 2003) are able to correctly reproduce the classical test of Kato and Phillips (1969) under favourable numerical conditions while some solutions may diverge depending on the degradation of the spatial and time discretization. The performances of turbulence models were then compared with data measured over a 1-year period (mid-2010 to mid-2011) at the PAPA station, located in the North Pacific Ocean. The modelled temperature and salinity were in good agreement with the observations, with a maximum temperature error between -2 and 2 °C during the stratified period (June to October). However, the results also depend on the numerical conditions. The vertical RMSE varied, for different turbulent closures, from 0.1 to 0.3 °C during the stratified period and from 0.03 to 0.15 °C during the homogeneous period. This 1-D configuration at the PAPA station (called PAPA1D) is now available in NEMO as a reference configuration including the input files and atmospheric forcing set described in this paper. Thus, all the results described can be recovered by downloading and launching PAPA1D. The configuration is described on the NEMO site (nemo-ocean.eu/Using-NEMO/Configurations/C1D_PAPA">http://www.nemo-ocean.eu/Using-NEMO/Configurations/C1D_PAPA). This package is a good starting point for further investigation of vertical processes.

Adapting NEMO for use as the UK operational storm surge forecasting model

NASA Astrophysics Data System (ADS)

Furner, Rachel; Williams, Jane; Horsburgh, Kevin; Saulter, Andrew

2016-04-01

The United Kingdom is an area vulnerable to damage due to storm surges, particularly the East Coast which suffered losses estimated at over £1 billion during the North Sea surge event of the 5th and 6th December 2013. Accurate forecasting of storm surge events for this region is crucial to enable government agencies to assess the risk of overtopping of coastal defences so they can respond appropriately, minimising risk to life and infrastructure. There has been an operational storm surge forecast service for this region since 1978, using a numerical model developed by the National Oceanography Centre (NOC) and run at the UK Met Office. This is also implemented as part of an ensemble prediction system, using perturbed atmospheric forcing to produce an ensemble surge forecast. In order to ensure efficient use of future supercomputer developments and to create synergy with existing operational coastal ocean models the Met Office and NOC have begun a joint project transitioning the storm surge forecast system from the current CS3X code base to a configuration based on the Nucleus for European Modelling of the Ocean (NEMO). This work involves both adapting NEMO to add functionality, such as allowing the drying out of ocean cells and changes allowing NEMO to run efficiently as a two-dimensional, barotropic model. As the ensemble surge forecast system is run with 12 members 4 times a day computational efficiency is of high importance. Upon completion this project will enable interesting scientific comparisons to be made between a NEMO based surge model and the full three-dimensional baroclinic NEMO based models currently run within the Met Office, facilitating assessment of the impact of baroclinic processes, and vertical resolution on sea surface height forecasts. Moving to a NEMO code base will also allow many future developments to be more easily used within the storm surge model due to the wide range of options which currently exist within NEMO or are planned for

NEMO educational kit on micro-optics at the secondary school

NASA Astrophysics Data System (ADS)

Flores-Arias, M. T.; Bao-Varela, Carmen

2014-07-01

NEMO was the "Network of Excellence in Micro-Optics" granted in the "Sixth Framework Program" of the European Union. It aimed at providing Europe with a complete Micro-Optics food-chain, by setting up centers for optical modeling and design; measurement and instrumentation; mastering, prototyping and replication; integration and packaging and reliability and standardization. More than 300 researchers from 30 groups in 12 countries participated in the project. One of the objectives of NEMO was to spread excellence and disseminate knowledge on micro-optics and micro-photonics. To convince pupils, already from secondary school level on, about the crucial role of light and micro-optics and the opportunities this combination holds, several partners of NEMO had collaborate to create this Educational Kit. In Spain the partner involved in this aim was the "Microoptics and GRIN Optics Group" at the University of Santiago of Compostela (USC). The educational kits provided to the Secondary School were composed by two plastic cards with the following microoptical element: different kinds of diffractive optical elements or DOES and refractive optical elements or ROEs namely arrays of micro-lenses. The kit also included a DVD with a handbook for performing the experiments as well as a laser pointer source. This kit was distributed free of charge in the countries with partners in NEMO. In particular in Spain was offered to around 200 Secondary School Centers and only 80 answered accepting evaluate the kit.

Surface wave effects in the NEMO ocean model: Forced and coupled experiments

NASA Astrophysics Data System (ADS)

Breivik, Øyvind; Mogensen, Kristian; Bidlot, Jean-Raymond; Balmaseda, Magdalena Alonso; Janssen, Peter A. E. M.

2015-04-01

The NEMO general circulation ocean model is extended to incorporate three physical processes related to ocean surface waves, namely the surface stress (modified by growth and dissipation of the oceanic wavefield), the turbulent kinetic energy flux from breaking waves, and the Stokes-Coriolis force. Experiments are done with NEMO in ocean-only (forced) mode and coupled to the ECMWF atmospheric and wave models. Ocean-only integrations are forced with fields from the ERA-Interim reanalysis. All three effects are noticeable in the extratropics, but the sea-state-dependent turbulent kinetic energy flux yields by far the largest difference. This is partly because the control run has too vigorous deep mixing due to an empirical mixing term in NEMO. We investigate the relation between this ad hoc mixing and Langmuir turbulence and find that it is much more effective than the Langmuir parameterization used in NEMO. The biases in sea surface temperature as well as subsurface temperature are reduced, and the total ocean heat content exhibits a trend closer to that observed in a recent ocean reanalysis (ORAS4) when wave effects are included. Seasonal integrations of the coupled atmosphere-wave-ocean model consisting of NEMO, the wave model ECWAM, and the atmospheric model of ECMWF similarly show that the sea surface temperature biases are greatly reduced when the mixing is controlled by the sea state and properly weighted by the thickness of the uppermost level of the ocean model. These wave-related physical processes were recently implemented in the operational coupled ensemble forecast system of ECMWF.

Withaferin A disrupts ubiquitin-based NEMO reorganization induced by canonical NF-κB signaling

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

Jackson, Shawn S.; Medical Scientist Training Program, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, WI 53705; Cellular and Molecular Biology Program, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, WI 53705

2015-02-01

The NF-κB family of transcription factors regulates numerous cellular processes, including cell proliferation and survival responses. The constitutive activation of NF-κB has also emerged as an important oncogenic driver in many malignancies, such as activated B-cell like diffuse large B cell lymphoma, among others. In this study, we investigated the impact and mechanisms of action of Withaferin A, a naturally produced steroidal lactone, against both signal-inducible as well as constitutive NF-κB activities. We found that Withaferin A is a robust inhibitor of canonical and constitutive NF-κB activities, leading to apoptosis of certain lymphoma lines. In the canonical pathway induced bymore » TNF, Withaferin A did not disrupt RIP1 polyubiquitination or NEMO–IKKβ interaction and was a poor direct IKKβ inhibitor, but prevented the formation of TNF-induced NEMO foci which colocalized with TNF ligand. While GFP-NEMO efficiently formed TNF-induced foci, a GFP-NEMO{sup Y308S} mutant that is defective in binding to polyubiquitin chains did not form foci. Our study reveals that Withaferin A is a novel type of IKK inhibitor which acts by disrupting NEMO reorganization into ubiquitin-based signaling structures in vivo. - Highlights: • Withaferin A, a NF-κB inhibitor, disrupts signaling induced NEMO localization, a novel point of inhibition. • NEMO can be localized to distinct signaling foci after treatment with TNF. • ABC-type DLCBL cells can be sensitized to apoptosis after treatment with Withaferin A.« less

Withaferin A disrupts ubiquitin-based NEMO reorganization induced by canonical NF-κB signaling.

PubMed

Jackson, Shawn S; Oberley, Christopher; Hooper, Christopher P; Grindle, Kreg; Wuerzberger-Davis, Shelly; Wolff, Jared; McCool, Kevin; Rui, Lixin; Miyamoto, Shigeki

2015-02-01

The NF-κB family of transcription factors regulates numerous cellular processes, including cell proliferation and survival responses. The constitutive activation of NF-κB has also emerged as an important oncogenic driver in many malignancies, such as activated B-cell like diffuse large B cell lymphoma, among others. In this study, we investigated the impact and mechanisms of action of Withaferin A, a naturally produced steroidal lactone, against both signal-inducible as well as constitutive NF-κB activities. We found that Withaferin A is a robust inhibitor of canonical and constitutive NF-κB activities, leading to apoptosis of certain lymphoma lines. In the canonical pathway induced by TNF, Withaferin A did not disrupt RIP1 polyubiquitination or NEMO-IKKβ interaction and was a poor direct IKKβ inhibitor, but prevented the formation of TNF-induced NEMO foci which colocalized with TNF ligand. While GFP-NEMO efficiently formed TNF-induced foci, a GFP-NEMO(Y308S) mutant that is defective in binding to polyubiquitin chains did not form foci. Our study reveals that Withaferin A is a novel type of IKK inhibitor which acts by disrupting NEMO reorganization into ubiquitin-based signaling structures in vivo. Copyright © 2014 Elsevier Inc. All rights reserved.

Status of NEMO

NASA Astrophysics Data System (ADS)

Migneco, E.; Aiello, S.; Ambriola, M.; Ameli, F.; Amore, I.; Anghinolfi, M.; Anzalone, A.; Barbarino, G.; Barbarito, E.; Battaglieri, M.; Bellotti, R.; Beverini, N.; Bonori, M.; Bouhdaef, B.; Brescia, M.; Cacopardo, G.; Cafagna, F.; Capone, A.; Caponetto, L.; Castorina, E.; Ceres, A.; Chiarusi, T.; Circella, M.; Cocimano, R.; Coniglione, R.; Cordelli, M.; Costa, M.; Cuneo, S.; D'Amico, A.; De Bonis, G.; De Marzo, C.; De Rosa, G.; De Vita, R.; Distefano, C.; Falchini, E.; Fiorello, C.; Flaminio, V.; Fratini, K.; Galeotti, S.; Gabrielli, A.; Gandolfi, E.; Giacomelli, G.; Grimaldi, A.; Habel, R.; Leonora, E.; Lonardo, A.; Longo, G.; Lo Presti, D.; Lucarelli, F.; Maccione, L.; Margiotta, A.; Martini, A.; Masullo, R.; Megna, R.; Mongelli, M.; Morganti, M.; Montaruli, T.; Musumeci, M.; Nicolau, C. A.; Orlando, A.; Osipenko, M.; Osteria, G.; Papaleo, R.; Pappalardo, V.; Petta, C.; Piattelli, P.; Raffaelli, F.; Raia, G.; Randazzo, N.; Reito, S.; Ricco, G.; Riccobene, G.; Ripani, M.; Rovelli, A.; Ruppi, M.; Russo, G. V.; Russo, S.; Sapienza, P.; Sedita, M.; Schuller, J.-P.; Shirokov, E.; Simeone, F.; Sipala, V.; Spurio, M.; Taiuti, M.; Terreni, G.; Trasatti, L.; Urso, S.; Valente, V.; Vicini, P.

2006-11-01

The activities towards the realization of a km3 Cherenkov neutrino detector carried out by the NEMO Collaboration are described. Long-term exploration of a 3500 m deep-sea site close to the Sicilian coast has shown that it is optimal for the installation of the detector. The realization of a Phase-1 project, which is under way, will validate the proposed technologies for the realization of the km3 detector on a Test Site at 2000 m depth. The realization of a new infrastructure on the candidate site (Phase-2 project) will provide the possibility to test detector components at 3500 m depth.

Systemic delivery of NEMO binding domain/IKKγ inhibitory peptide to young mdx mice improves dystrophic skeletal muscle histopathology.

PubMed

Reay, Daniel P; Yang, Michele; Watchko, Jon F; Daood, Molly; O'Day, Terrence L; Rehman, Khaleel K; Guttridge, Denis C; Robbins, Paul D; Clemens, Paula R

2011-09-01

The activation of nuclear factor κB (NF-κB) contributes to muscle degeneration that results from dystrophin deficiency in human Duchenne muscular dystrophy (DMD) and in the mdx mouse. In dystrophic muscle, NF-κB participates in inflammation and failure of muscle regeneration. Peptides containing the NF-κB Essential Modulator (NEMO) binding domain (NBD) disrupt the IκB kinase complex, thus blocking NF-κB activation. The NBD peptide, which is linked to a protein transduction domain to achieve in vivo peptide delivery to muscle tissue, was systemically delivered to mdx mice for 4 or 7 weeks to study NF-κB activation, histological changes in hind limb and diaphragm muscle and ex vivo function of diaphragm muscle. Decreased NF-κB activation, decreased necrosis and increased regeneration were observed in hind limb and diaphragm muscle in mdx mice treated systemically with NBD peptide, as compared to control mdx mice. NBD peptide treatment resulted in improved generation of specific force and greater resistance to lengthening activations in diaphragm muscle ex vivo. Together these data support the potential of NBD peptides for the treatment of DMD by modulating dystrophic pathways in muscle that are downstream of dystrophin deficiency. Published by Elsevier Inc.

AlignNemo: a local network alignment method to integrate homology and topology.

PubMed

Ciriello, Giovanni; Mina, Marco; Guzzi, Pietro H; Cannataro, Mario; Guerra, Concettina

2012-01-01

Local network alignment is an important component of the analysis of protein-protein interaction networks that may lead to the identification of evolutionary related complexes. We present AlignNemo, a new algorithm that, given the networks of two organisms, uncovers subnetworks of proteins that relate in biological function and topology of interactions. The discovered conserved subnetworks have a general topology and need not to correspond to specific interaction patterns, so that they more closely fit the models of functional complexes proposed in the literature. The algorithm is able to handle sparse interaction data with an expansion process that at each step explores the local topology of the networks beyond the proteins directly interacting with the current solution. To assess the performance of AlignNemo, we ran a series of benchmarks using statistical measures as well as biological knowledge. Based on reference datasets of protein complexes, AlignNemo shows better performance than other methods in terms of both precision and recall. We show our solutions to be biologically sound using the concept of semantic similarity applied to Gene Ontology vocabularies. The binaries of AlignNemo and supplementary details about the algorithms and the experiments are available at: sourceforge.net/p/alignnemo.

Target Specificity of the E3 Ligase LUBAC for Ubiquitin and NEMO Relies on Different Minimal Requirements*

PubMed Central

Smit, Judith J.; van Dijk, Willem J.; El Atmioui, Dris; Merkx, Remco; Ovaa, Huib; Sixma, Titia K.

2013-01-01

The ubiquitination of NEMO with linear ubiquitin chains by the E3-ligase LUBAC is important for the activation of the canonical NF-κB pathway. NEMO ubiquitination requires a dual target specificity of LUBAC, priming on a lysine on NEMO and chain elongation on the N terminus of the priming ubiquitin. Here we explore the minimal requirements for these specificities. Effective linear chain formation requires a precise positioning of the ubiquitin N-terminal amine in a negatively charged environment on the top of ubiquitin. Whereas the RBR-LDD region on HOIP is sufficient for targeting the ubiquitin N terminus, the priming lysine modification on NEMO requires catalysis by the RBR domain of HOIL-1L as well as the catalytic machinery of the RBR-LDD domains of HOIP. Consequently, target specificity toward NEMO is determined by multiple LUBAC components, whereas linear ubiquitin chain elongation is realized by a specific interplay between HOIP and ubiquitin. PMID:24030825

Naval EarthMap Observer (NEMO) Hyperspectral Remote Sensing Program

DTIC Science & Technology

2000-10-01

The NEMO hyperspectral remote sensing program will provide unclassified, space-based hyperspectral passive imagery at moderate resolution that offers substantial potential for direct use by Naval forces and the Civil Sector.

TNFα- and IKKβ-mediated TANK/I-TRAF phosphorylation: implications for interaction with NEMO/IKKγ and NF-κB activation

PubMed Central

Bonif, Marianne; Meuwis, Marie-Alice; Close, Pierre; Benoit, Valérie; Heyninck, Karen; Chapelle, Jean-Paul; Bours, Vincent; Merville, Marie-Paule; Piette, Jacques; Beyaert, Rudi; Chariot, Alain

2005-01-01

Pro-inflammatory cytokines trigger signalling cascades leading to NF-κB (nuclear factor-κB)-dependent gene expression through IKK [IκB (inhibitory κB) kinase]-dependent phosphorylation and subsequent degradation of the IκB proteins and via induced phosphorylation of p65. These signalling pathways rely on sequentially activated kinases which are assembled by essential and non-enzymatic scaffold proteins into functional complexes. Here, we show that the pro-inflammatory cytokine TNFα (tumour necrosis factor α) promotes TANK [TRAF (TNF receptor-associated factor) family member associated NF-κB activator] recruitment to the IKK complex via a newly characterized C-terminal zinc finger. Moreover, we show that TANK is phosphorylated by IKKβ upon TNFα stimulation and that this modification negatively regulates TANK binding to NEMO (NF-κB essential modulator). Interestingly, reduced TANK expression by RNA interference attenuates TNFα-mediated induction of a subset of NF-κB target genes through decreased p65 transactivation potential. Therefore the scaffold protein TANK is required for the cellular response to TNFα by connecting upstream signalling molecules to the IKKs and p65, and its subsequent IKKβ-mediated phosphorylation may be a mechanism to terminate the TANK-dependent wave of NF-κB activation. PMID:16336209

NEMOTAM: tangent and adjoint models for the ocean modelling platform NEMO

NASA Astrophysics Data System (ADS)

Vidard, A.; Bouttier, P.-A.; Vigilant, F.

2015-04-01

Tangent linear and adjoint models (TAMs) are efficient tools to analyse and to control dynamical systems such as NEMO. They can be involved in a large range of applications such as sensitivity analysis, parameter estimation or the computation of characteristic vectors. A TAM is also required by the 4D-Var algorithm, which is one of the major methods in data assimilation. This paper describes the development and the validation of the tangent linear and adjoint model for the NEMO ocean modelling platform (NEMOTAM). The diagnostic tools that are available alongside NEMOTAM are detailed and discussed, and several applications are also presented.

NEMOTAM: tangent and adjoint models for the ocean modelling platform NEMO

NASA Astrophysics Data System (ADS)

Vidard, A.; Bouttier, P.-A.; Vigilant, F.

2014-10-01

The tangent linear and adjoint model (TAM) are efficient tools to analyse and to control dynamical systems such as NEMO. They can be involved in a large range of applications such as sensitivity analysis, parameter estimation or the computation of characteristics vectors. TAM is also required by the 4-D-VAR algorithm which is one of the major method in Data Assimilation. This paper describes the development and the validation of the Tangent linear and Adjoint Model for the NEMO ocean modelling platform (NEMOTAM). The diagnostic tools that are available alongside NEMOTAM are detailed and discussed and several applications are also presented.

Sea-ice evaluation of NEMO-Nordic 1.0: a NEMO-LIM3.6-based ocean-sea-ice model setup for the North Sea and Baltic Sea

NASA Astrophysics Data System (ADS)

Pemberton, Per; Löptien, Ulrike; Hordoir, Robinson; Höglund, Anders; Schimanke, Semjon; Axell, Lars; Haapala, Jari

2017-08-01

The Baltic Sea is a seasonally ice-covered marginal sea in northern Europe with intense wintertime ship traffic and a sensitive ecosystem. Understanding and modeling the evolution of the sea-ice pack is important for climate effect studies and forecasting purposes. Here we present and evaluate the sea-ice component of a new NEMO-LIM3.6-based ocean-sea-ice setup for the North Sea and Baltic Sea region (NEMO-Nordic). The setup includes a new depth-based fast-ice parametrization for the Baltic Sea. The evaluation focuses on long-term statistics, from a 45-year long hindcast, although short-term daily performance is also briefly evaluated. We show that NEMO-Nordic is well suited for simulating the mean sea-ice extent, concentration, and thickness as compared to the best available observational data set. The variability of the annual maximum Baltic Sea ice extent is well in line with the observations, but the 1961-2006 trend is underestimated. Capturing the correct ice thickness distribution is more challenging. Based on the simulated ice thickness distribution we estimate the undeformed and deformed ice thickness and concentration in the Baltic Sea, which compares reasonably well with observations.

Withaferin A disrupts ubiquitin-based NEMO reorganization induced by canonical NF-κB signaling

PubMed Central

Jackson, Shawn S.; Oberley, Christopher; Hooper, Christopher P.; Grindle, Kreg; Wuerzberger-Davis, Shelly; Wolff, Jared; McCool, Kevin; Rui, Lixin; Miyamoto, Shigeki

2014-01-01

The NF-κB family of transcription factors regulates numerous cellular processes, including cell proliferation and survival responses. The constitutive activation of NF-κB has also emerged as an important oncogenic driver in many malignancies, such as activated B-cell like diffuse large B cell lymphoma, among others. In this study, we investigated the impact and mechanisms of action of Withaferin A, a naturally produced steroidal lactone, against both signal-inducible as well as constitutive NF-κB activities. We found that Withaferin A is a robust inhibitor of canonical and constitutive NF-κB activities, leading to apoptosis of certain lymphoma lines. In the canonical pathway induced by TNF, Withaferin A did not disrupt RIP1 polyubiquitination or NEMO-IKKβ interaction and was a poor direct IKKβ inhibitor, but prevented the formation of TNF induced NEMO foci which colocalized with TNF ligand. While GFP-NEMO efficiently formed TNF-induced foci, a GFP-NEMOY308S mutant that is defective in binding to polyubiquitin chains did not form foci. Our study reveals that Withaferin A is a novel type of IKK inhibitor which acts by disrupting NEMO reorganization into ubiquitin-based signaling structures in vivo. PMID:25304104

Noncanonical NF-κB Signaling Is Limited by Classical NF-κB Activity

PubMed Central

Gray, Carolyn M.; Remouchamps, Caroline; McCorkell, Kelly A.; Solt, Laura A.; Dejardin, Emmanuel; Orange, Jordan S.; May, Michael J.

2014-01-01

Precise regulation of nuclear factor κB (NF-κB) signaling is crucial for normal immune responses, and defective NF-κB activity underlies a range of immunodeficiencies. NF-κB is activated through two signaling cascades: the classical and noncanonical pathways. The classical pathway requires inhibitor of κB kinase β (IKKβ) and NF-κB essential modulator (NEMO), and hypomorphic mutations in the gene encoding NEMO (ikbkg) lead to inherited immunodeficiencies, collectively termed NEMO-ID. Noncanonical NF-κB activation requires NF-κB–inducing kinase (NIK) and IKKα, but not NEMO. We found that noncanonical NF-κB was basally active in peripheral blood mononuclear cells from NEMO-ID patients, and that noncanonical NF-κB signaling was similarly enhanced in cell lines lacking functional NEMO. NIK, which normally undergoes constitutive degradation, was aberrantly present in resting NEMO-deficient cells, and regulation of its abundance was rescued by reconstitution with full-length NEMO, but not a mutant NEMO protein unable to physically associate with IKKα or IKKβ. Binding of NEMO to IKKα was not required for ligand-dependent stabilization of NIK or noncanonical NF-κB signaling. Rather, an intact and functional IKK complex was essential to suppress basal NIK activity in unstimulated cells. Despite interacting with IKKα and IKKβ to form an IKK complex, NEMO mutants associated with immunodeficiency failed to rescue classical NF-κB signaling or reverse the accumulation of NIK. Together, these findings identify a crucial role for classical NF-κB activity in the suppression of basal noncanonical NF-κB signaling. PMID:24497610

Nemo:. a Project for a KM3 Underwater Detector for Astrophysical Neutrinos in the Mediterranean Sea

NASA Astrophysics Data System (ADS)

Amore, I.; Aiello, S.; Ambriola, M.; Ameli, F.; Anghinolfi, M.; Anzalone, A.; Barbarino, G.; Barbarito, E.; Battaglieri, M.; Bellotti, R.; Beverini, N.; Bonori, M.; Bouhadef, B.; Brescia, M.; Cacopardo, G.; Cafagna, F.; Capone, A.; Caponetto, L.; Castorina, E.; Ceres, A.; Chiarusi, T.; Circella, M.; Cocimano, R.; Coniglione, R.; Cordelli, M.; Costa, M.; Cuneo, S.; D'Amico, A.; de Bonis, G.; de Marzo, C.; de Rosa, G.; de Vita, R.; Distefano, C.; Falchini, E.; Fiorello, C.; Flaminio, V.; Fratini, K.; Gabrielli, A.; Galeotti, S.; Gandolfi, E.; Giacomelli, G.; Giorgi, F.; Grimaldi, A.; Habel, R.; Leonora, E.; Lonardo, A.; Longo, G.; Lo Presti, D.; Lucarelli, F.; Maccioni, E.; Margiotta, A.; Martini, A.; Masullo, R.; Megna, R.; Migneco, E.; Mongelli, M.; Montaruli, T.; Morganti, M.; Musumeci, M. S.; Nicolau, C. A.; Orlando, A.; Osipenko, M.; Osteria, G.; Papaleo, R.; Pappalardo, V.; Petta, C.; Piattelli, P.; Raia, G.; Randazzo, N.; Reito, S.; Ricco, G.; Riccobene, G.; Ripani, M.; Rovelli, A.; Ruppi, M.; Russo, G. V.; Russo, S.; Sapienza, P.; Sedita, M.; Shirokov, E.; Simeone, F.; Sipala, V.; Spurio, M.; Taiuti, M.; Terreni, G.; Trasatti, L.; Urso, S.; Valente, V.; Vicini, P.

The status of the project is described: the activity on long term characterization of water optical and oceanographic parameters at the Capo Passero site candidate for the Mediterranean km3 neutrino telescope; the feasibility study; the physics performances and underwater technology for the km3; the activity on NEMO Phase 1, a technological demonstrator that has been deployed at 2000 m depth 25 km offshore Catania; the realization of an underwater infrastructure at 3500 m depth at the candidate site (NEMO Phase 2).

Naval EarthMap Observer (NEMO) science and naval products

NASA Astrophysics Data System (ADS)

Davis, Curtiss O.; Kappus, Mary E.; Gao, Bo-Cai; Bissett, W. Paul; Snyder, William A.

1998-11-01

A wide variety of applications of imaging spectrometry have been demonstrated using data from aircraft systems. Based on this experience the Navy is pursuing the Hyperspectral Remote Sensing Technology (HRST) Program to use hyperspectral imagery to characterize the littoral environment, for scientific and environmental studies and to meet Naval needs. To obtain the required space based hyperspectral imagery the Navy has joined in a partnership with industry to build and fly the Naval EarthMap Observer (NEMO). The NEMO spacecraft has the Coastal Ocean Imaging Spectrometer (COIS) a hyperspectral imager with adequate spectral and spatial resolution and a high signal-to- noise ratio to provide long term monitoring and real-time characterization of the coastal environment. It includes on- board processing for rapid data analysis and data compression, a large volume recorder, and high speed downlink to handle the required large volumes of data. This paper describes the algorithms for processing the COIS data to provide at-launch ocean data products and the research and modeling that are planned to use COIS data to advance our understanding of the dynamics of the coastal ocean.

Measurement of the atmospheric muon flux with the NEMO Phase-1 detector

NASA Astrophysics Data System (ADS)

Aiello, S.; Ameli, F.; Amore, I.; Anghinolfi, M.; Anzalone, A.; Barbarino, G.; Battaglieri, M.; Bazzotti, M.; Bersani, A.; Beverini, N.; Biagi, S.; Bonori, M.; Bouhadef, B.; Brunoldi, M.; Cacopardo, G.; Capone, A.; Caponetto, L.; Carminati, G.; Chiarusi, T.; Circella, M.; Cocimano, R.; Coniglione, R.; Cordelli, M.; Costa, M.; D'Amico, A.; De Bonis, G.; De Marzo, C.; De Rosa, G.; De Ruvo, G.; De Vita, R.; Distefano, C.; Falchini, E.; Flaminio, V.; Fratini, K.; Gabrielli, A.; Galatà, S.; Gandolfi, E.; Giacomelli, G.; Giorgi, F.; Giovanetti, G.; Grimaldi, A.; Habel, R.; Imbesi, M.; Kulikovsky, V.; Lattuada, D.; Leonora, E.; Lonardo, A.; Lo Presti, D.; Lucarelli, F.; Marinelli, A.; Margiotta, A.; Martini, A.; Masullo, R.; Migneco, E.; Minutoli, S.; Morganti, M.; Musico, P.; Musumeci, M.; Nicolau, C. A.; Orlando, A.; Osipenko, M.; Papaleo, R.; Pappalardo, V.; Piattelli, P.; Piombo, D.; Raia, G.; Randazzo, N.; Reito, S.; Ricco, G.; Riccobene, G.; Ripani, M.; Rovelli, A.; Ruppi, M.; Russo, G. V.; Russo, S.; Sapienza, P.; Sciliberto, D.; Sedita, M.; Shirokov, E.; Simeone, F.; Sipala, V.; Spurio, M.; Taiuti, M.; Trasatti, L.; Urso, S.; Vecchi, M.; Vicini, P.; Wischnewski, R.

2010-05-01

The NEMO Collaboration installed and operated an underwater detector including prototypes of the critical elements of a possible underwater km 3 neutrino telescope: a four-floor tower (called Mini-Tower) and a Junction Box. The detector was developed to test some of the main systems of the km 3 detector, including the data transmission, the power distribution, the timing calibration and the acoustic positioning systems as well as to verify the capabilities of a single tridimensional detection structure to reconstruct muon tracks. We present results of the analysis of the data collected with the NEMO Mini-Tower. The position of photomultiplier tubes (PMTs) is determined through the acoustic position system. Signals detected with PMTs are used to reconstruct the tracks of atmospheric muons. The angular distribution of atmospheric muons was measured and results compared to Monte Carlo simulations.

Successful treatment with infliximab for inflammatory colitis in a patient with X-linked anhidrotic ectodermal dysplasia with immunodeficiency.

PubMed

Mizukami, Tomoyuki; Obara, Megumi; Nishikomori, Ryuta; Kawai, Tomoki; Tahara, Yoshihiro; Sameshima, Naoki; Marutsuka, Kousuke; Nakase, Hiroshi; Kimura, Nobuhiro; Heike, Toshio; Nunoi, Hiroyuki

2012-02-01

X-linked anhidrotic ectodermal dysplasia with immunodeficiency (X-EDA-ID) is caused by hypomorphic mutations in the gene encoding nuclear factor-κB essential modulator protein (NEMO). Patients are susceptibile to diverse pathogens due to insufficient cytokine and frequently show severe chronic colitis. An 11-year-old boy with X-EDA-ID was hospitalized with autoimmune symptoms and severe chronic colitis which had been refractory to immunosuppressive drugs. Since tumor necrosis factor (TNF) α is responsible for the pathogenesis of NEMO colitis according to intestinal NEMO and additional TNFR1 knockout mice studies, and high levels of TNFα-producing mononuclear cells were detected in the patient due to the unexpected gene reversion mosaicism of NEMO, an anti-TNFα monoclonal antibody was administered to ameliorate his abdominal symptoms. Repeated administrations improved his colonoscopic findings as well as his dry skin along with a reduction of TNFα-expressing T cells. These findings suggest TNF blockade therapy is of value for refractory NEMO colitis with gene reversion.

Requirement of FADD, NEMO, and BAX/BAK for Aberrant Mitochondrial Function in Tumor Necrosis Factor Alpha-Induced Necrosis▿

PubMed Central

Irrinki, Krishna M.; Mallilankaraman, Karthik; Thapa, Roshan J.; Chandramoorthy, Harish C.; Smith, Frank J.; Jog, Neelakshi R.; Gandhirajan, Rajesh Kumar; Kelsen, Steven G.; Houser, Steven R.; May, Michael J.; Balachandran, Siddharth; Madesh, Muniswamy

2011-01-01

Necroptosis represents a form of alternative programmed cell death that is dependent on the kinase RIP1. RIP1-dependent necroptotic death manifests as increased reactive oxygen species (ROS) production in mitochondria and is accompanied by loss of ATP biogenesis and eventual dissipation of mitochondrial membrane potential. Here, we show that tumor necrosis factor alpha (TNF-α)-induced necroptosis requires the adaptor proteins FADD and NEMO. FADD was found to mediate formation of the TNF-α-induced pronecrotic RIP1-RIP3 kinase complex, whereas the IκB Kinase (IKK) subunit NEMO appears to function downstream of RIP1-RIP3. Interestingly, loss of RelA potentiated TNF-α-dependent necroptosis, indicating that NEMO regulates necroptosis independently of NF-κB. Using both pharmacologic and genetic approaches, we demonstrate that the overexpression of antioxidants alleviates ROS elevation and necroptosis. Finally, elimination of BAX and BAK or overexpression of Bcl-xL protects cells from necroptosis at a later step. These findings provide evidence that mitochondria play an amplifying role in inflammation-induced necroptosis. PMID:21746883

Comparative study of Arctic sea ice response from NEMO-LIM3 to two different atmospheric forcings

NASA Astrophysics Data System (ADS)

Massonnet, Francois; Fichefet, Thierry; Goosse, Hugues; Mathiot, Pierre; König Beatty, Christof; Vancoppenolle, Martin

2010-05-01

Sea ice plays a key role within the climate system as it is, e.g., an efficient barrier to transfers of heat, mass and momentum between atmosphere and ocean. In order to simulate the observed sea ice state, global Ocean General Circulation Models (OGCMs) must benefit from good quality atmospheric forcings. NEMO-LIM3 is one of those OGCMs. This model results from the coupling of the sea ice model LIM3 with the ocean model OPA. So far, the NCEP/NCAR reanalysis dataset (2-m atmospheric temperatures and 10-m wind speeds) has been used jointly with monthly climatologies of relative humidity, cloudiness and precipitation to set up and calibrate NEMO-LIM3. Clear biases in model outputs have been tentatively attributed to this forcing. Here, we investigate the consequences of using the ERA-40-based DFS4 forcing on an ORCA1 configuration (1° resolution), with focus on the Arctic sea ice. Using an adequate metric, we measure the discrepancies between the simulations resulting from the respective forcings. A particular attention is paid to the sea ice features along Siberia at the beginning of the 80s, as previous NEMO-LIM3 runs with the NCEP/NCAR forcing exhibit a significant overestimation of ice extent in this area during this time period.

Long term monitoring of the optical background in the Capo Passero deep-sea site with the NEMO tower prototype

NASA Astrophysics Data System (ADS)

Adrián-Martínez, S.; Aiello, S.; Ameli, F.; Anghinolfi, M.; Ardid, M.; Barbarino, G.; Barbarito, E.; Barbato, F. C. T.; Beverini, N.; Biagi, S.; Biagioni, A.; Bouhadef, B.; Bozza, C.; Cacopardo, G.; Calamai, M.; Calì, C.; Calvo, D.; Capone, A.; Caruso, F.; Ceres, A.; Chiarusi, T.; Circella, M.; Cocimano, R.; Coniglione, R.; Costa, M.; Cuttone, G.; D'Amato, C.; D'Amico, A.; De Bonis, G.; De Luca, V.; Deniskina, N.; De Rosa, G.; di Capua, F.; Distefano, C.; Enzenhöfer, A.; Fermani, P.; Ferrara, G.; Flaminio, V.; Fusco, L. A.; Garufi, F.; Giordano, V.; Gmerk, A.; Grasso, R.; Grella, G.; Hugon, C.; Imbesi, M.; Kulikovskiy, V.; Lahmann, R.; Larosa, G.; Lattuada, D.; Leismüller, K. P.; Leonora, E.; Litrico, P.; Llorens Alvarez, C. D.; Lonardo, A.; Longhitano, F.; Lo Presti, D.; Maccioni, E.; Margiotta, A.; Marinelli, A.; Martini, A.; Masullo, R.; Migliozzi, P.; Migneco, E.; Miraglia, A.; Mollo, C. M.; Mongelli, M.; Morganti, M.; Musico, P.; Musumeci, M.; Nicolau, C. A.; Orlando, A.; Orzelli, A.; Papaleo, R.; Pellegrino, C.; Pellegriti, M. G.; Perrina, C.; Piattelli, P.; Pugliatti, C.; Pulvirenti, S.; Raffaelli, F.; Randazzo, N.; Real, D.; Riccobene, G.; Rovelli, A.; Saldaña, M.; Sanguineti, M.; Sapienza, P.; Sciacca, V.; Sgura, I.; Simeone, F.; Sipala, V.; Speziale, F.; Spitaleri, A.; Spurio, M.; Stellacci, S. M.; Taiuti, M.; Terreni, G.; Trasatti, L.; Trovato, A.; Ventura, C.; Vicini, P.; Viola, S.; Vivolo, D.

2016-02-01

The NEMO Phase-2 tower is the first detector which was operated underwater for more than 1 year at the "record" depth of 3500 m. It was designed and built within the framework of the NEMO (NEutrino Mediterranean Observatory) project. The 380 m high tower was successfully installed in March 2013 80 km offshore Capo Passero (Italy). This is the first prototype operated on the site where the Italian node of the KM3NeT neutrino telescope will be built. The installation and operation of the NEMO Phase-2 tower has proven the functionality of the infrastructure and the operability at 3500 m depth. A more than 1 year long monitoring of the deep water characteristics of the site has been also provided. In this paper the infrastructure and the tower structure and instrumentation are described. The results of long term optical background measurements are presented. The rates show stable and low baseline values, compatible with the contribution of ^{40}K light emission, with a small percentage of light bursts due to bioluminescence. All these features confirm the stability and good optical properties of the site.

Evaluation of the coupled COSMO-CLM+NEMO-Nordic model with focus on North and Baltic seas

NASA Astrophysics Data System (ADS)

Lenhardt, J.; Pham, T. V.; Früh, B.; Brauch, J.

2017-12-01

The region east of the Baltic Sea has been identified as a hot-spot of climate change by Giorgi, 2006, on the base of temperature and precipitation variability. For this purpose, the atmosphere model COSMO-CLM has been coupled to the ocean model NEMO, including the sea ice model LIM3, via the OASIS3-MCT coupler (Pham et al., 2014). The coupler interpolates heat, fresh water, momentum fluxes, sea level pressure and the fraction of sea ice at the interface in space and time. Our aim is to find an optimal configuration of the already existing coupled regional atmospheric-ocean model COSMO-CLM+NEMO-Nordic. So far results for the North- and Baltic seas show that the coupled run has large biases compared with the E-OBS reference data. Therefore, additional simulation evaluations are planned by the use of independent satellite observation data (e.g. Copernicus, EURO4M). We have performed a series of runs with the coupled COSMO-CLM+NEMO-Nordic model to find out about differences of model outputs due to different coupling time steps. First analyses of COSMO-CLM 2m temperatures let presume that different coupling time steps have an impact on the results of the coupled model run. Additional tests over a longer period of time are conducted to understand whether the signal-to-noise ratio could influence the bias. The results will be presented in our poster.

Emotion modulation of the startle reflex in essential tremor: Blunted reactivity to unpleasant and pleasant pictures.

PubMed

Lafo, Jacob A; Mikos, Ania; Mangal, Paul C; Scott, Bonnie M; Trifilio, Erin; Okun, Michael S; Bowers, Dawn

2017-01-01

Essential tremor is a highly prevalent movement disorder characterized by kinetic tremor and mild cognitive-executive changes. These features are commonly attributed to abnormal cerebellar changes, resulting in disruption of cerebellar-thalamo-cortical networks. Less attention has been paid to alterations in basic emotion processing in essential tremor, despite known cerebellar-limbic interconnectivity. In the current study, we tested the hypothesis that a psychophysiologic index of emotional reactivity, the emotion modulated startle reflex, would be muted in individuals with essential tremor relative to controls. Participants included 19 essential tremor patients and 18 controls, who viewed standard sets of unpleasant, pleasant, and neutral pictures for six seconds each. During picture viewing, white noise bursts were binaurally presented to elicit startle eyeblinks measured over the orbicularis oculi. Consistent with past literature, controls' startle eyeblink responses were modulated according to picture valence (unpleasant > neutral > pleasant). In essential tremor participants, startle eyeblinks were not modulated by emotion. This modulation failure was not due to medication effects, nor was it due to abnormal appraisal of emotional picture content. Neuroanatomically, it remains unclear whether diminished startle modulation in essential tremor is secondary to aberrant cerebellar input to the amygdala, which is involved in priming the startle response in emotional contexts, or due to more direct disruption between the cerebellum and brainstem startle circuitry. If the former is correct, these findings may be the first to reveal dysregulation of emotional networks in essential tremor. Copyright © 2016 Elsevier Ltd. All rights reserved.

The NeMO Explorer Web Site: Interactive Exploration of a Recent Submarine Eruption and Hydrothermal Vents, Axial Volcano, Juan de Fuca Ridge

NASA Astrophysics Data System (ADS)

Weiland, C.; Chadwick, W. W.; Embley, R. W.

2001-12-01

To help visualize the submarine volcanic landscape at NOAA's New Millennium Observatory (NeMO), we have created the NeMO Explorer web site: http://www.pmel.noaa.gov/vents/nemo/explorer.html. This web site takes visitors a mile down beneath the ocean surface to explore Axial Seamount, an active submarine volcano 300 miles off the Oregon coast. We use virtual reality to put visitors in a photorealistic 3-D model of the seafloor that lets them view hydrothermal vents and fresh lava flows as if they were really on the seafloor. At each of six virtual sites there is an animated tour and a 360o panorama in which users can view the volcanic landscape and see biological communities within a spatially accurate context. From the six sites there are hyperlinks to 50 video clips taken by a remotely operated vehicle. Each virtual site concentrates on a different topic, including the dynamics of the 1998 eruption at Axial volcano (Rumbleometer), high-temperature hydrothermal vents (CASM and ASHES), diffuse hydrothermal venting (Marker33), subsurface microbial blooms (The Pit), and the boundary between old and new lavas (Castle vent). In addition to exploring the region geographically, visitors can also explore the web site via geological concepts. The concepts gallery lets you quickly find information about mid-ocean ridges, hydrothermal vents, vent fauna, lava morphology, and more. Of particular interest is an animation of the January 1998 eruption, which shows the rapid inflation (by over 3 m) and draining of the sheet flow. For more info see Fox et al., Nature, v.412, p.727, 2001. This project was funded by NOAA's High Performance Computing and Communication (HPCC) and Vents Programs. Our goal is to present a representative portion of the vast collection of NOAA's multimedia imagery to the public in a way that is easy to use and understand. These data are particularly challenging to present because of their high data rates and low contextual information. The 3-D models create

The SuperNemo ββ0ν enriched 82Se source foils and their radiopurity measurement with the BiPo-3 detector

NASA Astrophysics Data System (ADS)

Loaiza, P.; SuperNemo Collaboration

2017-09-01

The SuperNemo collaboration is currently building the SuperNemo demonstrator at the Modane Underground Laboratory, as the proof of concept for the full SuperNemo program. The enriched ββ0ν source consisting of thin foils containing 7 kg of 82Se is enclosed by the gas tracker and the plastic scintillator calorimeter. The full reconstruction of the ββ0ν event topology ensures an excellent background rejection and points at a true zero-background search. One of the most critical sources of background is a contamination in the source foils. The required radiopurity is 208Tl < 2 µBq/kg and 214Bi < 10 µBq/kg to achieve the sensitivity T1/2(ββ0ν) > 1026 years. The collaboration has developed a dedicated detector to measure the ultra high natural radiopurities requested, the BiPo-3 detector, installed in the Canfranc Underground Laboratory. The experimental design and performances of BiPo-3 are presented. Dedicated background measurements have been performed. After an exposure of about 2 years.m2 the surface activities of the scintillators of A(208Tl) = 1.0 ± 0.2 µBq/m2 and A(214Bi) = 1.0 ± 0.3 µBq/m2 are measured. Results of the 208Tl and 214Bi activity measurements of the first enriched 82Se foils of SuperNemo are also presented.

Coarsening of physics for biogeochemical model in NEMO

NASA Astrophysics Data System (ADS)

Bricaud, Clement; Le Sommer, Julien; Madec, Gurvan; Deshayes, Julie; Chanut, Jerome; Perruche, Coralie

2017-04-01

Ocean mesoscale and submesoscale turbulence contribute to ocean tracer transport and to shaping ocean biogeochemical tracers distribution. Representing adequately tracer transport in ocean models therefore requires to increase model resolution so that the impact of ocean turbulence is adequately accounted for. But due to supercomputers power and storage limitations, global biogeochemical models are not yet run routinely at eddying resolution. Still, because the "effective resolution" of eddying ocean models is much coarser than the physical model grid resolution, tracer transport can be reconstructed to a large extent by computing tracer transport and diffusion with a model grid resolution close to the effective resolution of the physical model. This observation has motivated the implementation of a new capability in NEMO ocean model (http://www.nemo-ocean.eu/) that allows to run the physical model and the tracer transport model at different grid resolutions. In a first time, we present results obtained with this new capability applied to a synthetic age tracer in a global eddying model configuration. In this model configuration, ocean dynamic is computed at ¼° resolution but tracer transport is computed at 3/4° resolution. The solution obtained is compared to 2 reference setup ,one at ¼° resolution for both physics and passive tracer models and one at 3/4° resolution for both physics and passive tracer model. We discuss possible options for defining the vertical diffusivity coefficient for the tracer transport model based on information from the high resolution grid. We describe the impact of this choice on the distribution and one the penetration of the age tracer. In a second time we present results obtained by coupling the physics with the biogeochemical model PISCES. We look at the impact of this methodology on some tracers distribution and dynamic. The method described here can found applications in ocean forecasting, such as the Copernicus Marine

Unusual Father-to-Daughter Transmission of Incontinentia Pigmenti Due to Mosaicism in IP Males.

PubMed

Fusco, Francesca; Conte, Matilde Immacolata; Diociaiuti, Andrea; Bigoni, Stefania; Branda, Maria Francesca; Ferlini, Alessandra; El Hachem, Maya; Ursini, Matilde Valeria

2017-09-01

Incontinentia pigmenti (IP; Online Mendelian Inheritance in Man catalog #308300) is an X-linked dominant ectodermal disorder caused by mutations of the inhibitor of κ polypeptide gene enchancer in B cells, kinase γ ( IKBKG )/ nuclear factor κB, essential modulator ( NEMO ) gene. Hemizygous IKBKG/NEMO loss-of-function (LoF) mutations are lethal in males, thus patients are female, and the disease is always transmitted from an IP-affected mother to her daughter. We present 2 families with father-to-daughter transmission of IP and provide for the first time molecular evidence that the combination of somatic and germ-line mosaicism for IKBKG/NEMO loss of function mutations in IP males resulted in the transmission of the disease to a female child. We searched for the IKBKG/NEMO mutant allele in blood, urine, skin, and sperm DNA and found that the 2 fathers were somatic and germ-line mosaics for the p.Gln132×mutation or the exon 4-10 deletion of IKBKG/NEMO , respectively. The highest level of IKBKG/NEMO mutant cells was detected in the sperm, which might explain the recurrence of the disease. We therefore recommend careful clinical evaluation in IP male cases and the genetic investigation in sperm DNA to ensure correct genetic counseling and prevent the risk of paternal transmission of IP. Copyright © 2017 by the American Academy of Pediatrics.

Tuning without over-tuning: parametric uncertainty quantification for the NEMO ocean model

NASA Astrophysics Data System (ADS)

Williamson, Daniel B.; Blaker, Adam T.; Sinha, Bablu

2017-04-01

In this paper we discuss climate model tuning and present an iterative automatic tuning method from the statistical science literature. The method, which we refer to here as iterative refocussing (though also known as history matching), avoids many of the common pitfalls of automatic tuning procedures that are based on optimisation of a cost function, principally the over-tuning of a climate model due to using only partial observations. This avoidance comes by seeking to rule out parameter choices that we are confident could not reproduce the observations, rather than seeking the model that is closest to them (a procedure that risks over-tuning). We comment on the state of climate model tuning and illustrate our approach through three waves of iterative refocussing of the NEMO (Nucleus for European Modelling of the Ocean) ORCA2 global ocean model run at 2° resolution. We show how at certain depths the anomalies of global mean temperature and salinity in a standard configuration of the model exceeds 10 standard deviations away from observations and show the extent to which this can be alleviated by iterative refocussing without compromising model performance spatially. We show how model improvements can be achieved by simultaneously perturbing multiple parameters, and illustrate the potential of using low-resolution ensembles to tune NEMO ORCA configurations at higher resolutions.

Remedying excessive numerical diapycnal mixing in a global 0.25° NEMO configuration

NASA Astrophysics Data System (ADS)

Megann, Alex; Nurser, George; Storkey, Dave

2016-04-01

If numerical ocean models are to simulate faithfully the upwelling branches of the global overturning circulation, they need to have a good representation of the diapycnal mixing processes which contribute to conversion of the bottom and deep waters produced in high latitudes into less dense watermasses. It is known that the default class of depth-coordinate ocean models such as NEMO and MOM5, as used in many state-of-the art coupled climate models and Earth System Models, have excessive numerical diapycnal mixing, resulting from irreversible advection across coordinate surfaces. The GO5.0 configuration of the NEMO ocean model, on an "eddy-permitting" 0.25° global grid, is used in the current UK GC1 and GC2 coupled models. Megann and Nurser (2016) have shown, using the isopycnal watermass analysis of Lee et al (2002), that spurious numerical mixing is substantially larger than the explicit mixing prescribed by the mixing scheme used by the model. It will be shown that increasing the biharmonic viscosity by a factor of three tends to suppress small-scale noise in the vertical velocity in the model. This significantly reduces the numerical mixing in GO5.0, and we shall show that it also leads to large-scale improvements in model biases.

The km 3 Mediterranean neutrino observatory - the NEMO.RD project

NASA Astrophysics Data System (ADS)

De Marzo, C. N.

2001-05-01

The NEMO.RD Project is a feasibility study of a km 3 underwater telescope for high energy astrophysical neutrinos to be located in the Mediterranean Sea. Results on various issues of this project are presented on: i) Monte Carlo simulation study of the capabilities of various arrays of phototubes in order to determine the detector geometry that can optimize performance and cost; ii) oceanographic survey of various sites in search of the optimal one; iii) feasibility study of mechanics, deployment, connections and maintenance of such a detector. Parameters of a site near Capo Passero, Sicily, where depth, transparency and other water parameters seem optimal are shown.

NEMO-SMO acoustic array: A deep-sea test of a novel acoustic positioning system for a km3-scale underwater neutrino telescope

NASA Astrophysics Data System (ADS)

Viola, S.; Ardid, M.; Bertin, V.; Enzenhöfer, A.; Keller, P.; Lahmann, R.; Larosa, G.; Llorens, C. D.; NEMO Collaboration; SMO Collaboration

2013-10-01

Within the activities of the NEMO project, the installation of a 8-floors tower (NEMO-Phase II) at a depth of 3500 m is foreseen in 2012. The tower will be installed about 80 km off-shore Capo Passero, in Sicily. On board the NEMO tower, an array of 18 acoustic sensors will be installed, permitting acoustic detection of biological sources, studies for acoustic neutrino detection and primarily acoustic positioning of the underwater structures. For the latter purpose, the sensors register acoustic signals emitted by five acoustic beacons anchored on the sea-floor. The data acquisition system of the acoustic sensors is fully integrated with the detector data transport system and is based on an “all data to shore” philosophy. Signals coming from hydrophones are continuously sampled underwater at 192 kHz/24 bit and transmitted to shore through an electro-optical cable for real-time analysis. A novel technology for underwater GPS time-stamping of data has been implemented and tested. The operation of the acoustic array will permit long-term test of sensors and electronics technologies that are proposed for the acoustic positioning system of KM3NeT.

Vapor Measurement System of Essential Oil Based on MOS Gas Sensors Driven with Advanced Temperature Modulation Technique

NASA Astrophysics Data System (ADS)

Sudarmaji, A.; Margiwiyatno, A.; Ediati, R.; Mustofa, A.

2018-05-01

The aroma/vapor of essential oils is complex compound which depends on the content of the gases and volatiles generated from essential oil. This paper describes a design of quick, simple, and low-cost static measurement system to acquire vapor profile of essential oil. The gases and volatiles are captured in a chamber by means of 9 MOS gas sensors which driven with advance temperature modulation technique. A PSoC CY8C28445-24PVXI based-interface unit is built to generate the modulation signal and acquire all sensor output into computer wirelessly via radio frequency serial communication using Digi International Inc., XBee (IEEE 802.15.4) through developed software under Visual.Net. The system was tested to measure 2 kinds of essential oil (Patchouli and Clove Oils) in 4 temperature modulations (without, 0.25 Hz, 1 Hz, and 4 Hz). A cycle measurement consists of reference and sample measurement sequentially which is set during 2 minutes in every 1 second respectively. It is found that the suitable modulation is 0,25Hz; 75%, and the results of Principle Component Analysis show that the system is able to distinguish clearly between Patchouli Oil and Clove Oil.

Dynamic Network-Based Relevance Score Reveals Essential Proteins and Functional Modules in Directed Differentiation

PubMed Central

Wu, Chia-Chou; Lin, Che

2015-01-01

The induction of stem cells toward a desired differentiation direction is required for the advancement of stem cell-based therapies. Despite successful demonstrations of the control of differentiation direction, the effective use of stem cell-based therapies suffers from a lack of systematic knowledge regarding the mechanisms underlying directed differentiation. Using dynamic modeling and the temporal microarray data of three differentiation stages, three dynamic protein-protein interaction networks were constructed. The interaction difference networks derived from the constructed networks systematically delineated the evolution of interaction variations and the underlying mechanisms. A proposed relevance score identified the essential components in the directed differentiation. Inspection of well-known proteins and functional modules in the directed differentiation showed the plausibility of the proposed relevance score, with the higher scores of several proteins and function modules indicating their essential roles in the directed differentiation. During the differentiation process, the proteins and functional modules with higher relevance scores also became more specific to the neuronal identity. Ultimately, the essential components revealed by the relevance scores may play a role in controlling the direction of differentiation. In addition, these components may serve as a starting point for understanding the systematic mechanisms of directed differentiation and for increasing the efficiency of stem cell-based therapies. PMID:25977693

First results from the NEMO Test Site

NASA Astrophysics Data System (ADS)

Riccobene, Giorgio; NEMO Collaboration

2007-03-01

The NEMO (NEutrino Mediterranean Observatory) Collaboration is constructing, 25 km E from Catania (Sicily) at 2000 m depth, an underwater test site to perform long-term tests of prototypes and new technologies for an underwater high energy neutrino detector in the Mediterranean Sea. In this framework the collaboration deployed and operated an experimental apparatus for on-line monitoring of deep-sea noise. The station is equipped with 4 hydrophones operational in the range 30 Hz - 40 kHz. This interval of frequencies matches the range suitable for acoustic detection of high energy neutrino-induced showers in water. Hydrophone signals are digitized underwater at 96 kHz sampling frequency and 24 bits resolution. A custom software was developed to record data on high resolution 4-channels PCM .le. Data are used to model underwater acoustic noise as a function of frequency and time, a mandatory parametre for future acoustic neutrino detectors. Results indicate that the average noise in the site is compatible with noise produced in condition of sea surface agitation (sea state.)

Development from the seafloor to the sea surface of the cabled NEMO-SN1 observatory in the Western Ionian Sea

NASA Astrophysics Data System (ADS)

Sparnocchia, Stefania; Beranzoli, Laura; Borghini, Mireno; Durante, Sara; Favali, Paolo; Giovanetti, Gabriele; Italiano, Francesco; Marinaro, Giuditta; Meccia, Virna; Papaleo, Riccardo; Riccobene, Giorgio; Schroeder, Katrin

2015-04-01

implementation of new measurement capabilities at seafloor and along the water column with sensors for measurements of physical-chemical (pressure, temperature, salinity, dissolved oxygen, turbidity, pCO2, currents) and geophysical (magnetometer, seismometer and gravity meter) parameters. An imaging system for deep sea fauna will be deployed very soon at TSS. Furthermore, the data acquisition/elaboration system will be enhanced, and data will be shared in near real time through the Catania node of the high-speed telecommunication network for University and Scientific Research. An Open Access policy is adopted to favour the access of the international scientific community. According to the EMSO business plan and EC recommendations, the enhanced infrastructure will be open to scientists, companies and public actors on excellence research basis, for the development of innovative scientific and technological research products. The existing seafloor module is already offering this service under the TNA program of FixO3 EC Project (www.fixo3.eu). The ongoing development of NEMO-SN1 will strengthen its capabilities to monitor long-term variability of key physical, geophysical and biogeochemical parameters, with applications, for example, in studies on modifications of the properties of water masses and the marine circulation, changes in marine chemistry, with particular emphasis on the carbon system and its role in ocean acidification, evolving trends in global sea level, and to address geo-hazards issues, such as earthquake and tsunami risks, volcanic risk, instability and collapse of the slopes.

SENP1-mediated NEMO deSUMOylation in adipocytes limits inflammatory responses and type-1 diabetes progression

PubMed Central

Shao, Lan; Zhou, Huanjiao Jenny; Zhang, Haifeng; Qin, Lingfeng; Hwa, John; Yun, Zhong; Ji, Weidong; Min, Wang

2015-01-01

Adipocyte dysfunction correlates with the development of diabetes. Here we show that mice with a adipocyte-specific deletion of the SUMO-specific protease SENP1 gene develop symptoms of type-1 diabetes mellitus (T1DM), including hyperglycaemia and glucose intolerance with mild insulin resistance. Peri-pancreatic adipocytes from SENP1-deficient mice exhibit heightened NF-κB activity and production of proinflammatory cytokines, which induce CCL5 expression in adjacent pancreatic islets and direct cytotoxic effects on pancreatic islets. Mechanistic studies show that SENP1 deletion in adipocytes enhances SUMOylation of the NF-κB essential molecule, NEMO, at lysine 277/309, leading to increased NF-κB activity, cytokine production and pancreatic inflammation. We further show that NF-κB inhibitors could inhibit pre-diabetic cytokine production, β-cell damages and ameliorate the T1DM phenotype in SENP1-deficient mice. Feeding a high-fat diet augments both type-1 and type-2 diabetes phenotypes in SENP1-deficient mice, consistent with the effects on adipocyte-derived NF-κB and cytokine signalling. Our study reveals previously unrecognized mechanism regulating the onset and progression of T1DM associated with adipocyte dysfunction. PMID:26596471

SENP1-mediated NEMO deSUMOylation in adipocytes limits inflammatory responses and type-1 diabetes progression.

PubMed

Shao, Lan; Zhou, Huanjiao Jenny; Zhang, Haifeng; Qin, Lingfeng; Hwa, John; Yun, Zhong; Ji, Weidong; Min, Wang

2015-11-24

Adipocyte dysfunction correlates with the development of diabetes. Here we show that mice with a adipocyte-specific deletion of the SUMO-specific protease SENP1 gene develop symptoms of type-1 diabetes mellitus (T1DM), including hyperglycaemia and glucose intolerance with mild insulin resistance. Peri-pancreatic adipocytes from SENP1-deficient mice exhibit heightened NF-κB activity and production of proinflammatory cytokines, which induce CCL5 expression in adjacent pancreatic islets and direct cytotoxic effects on pancreatic islets. Mechanistic studies show that SENP1 deletion in adipocytes enhances SUMOylation of the NF-κB essential molecule, NEMO, at lysine 277/309, leading to increased NF-κB activity, cytokine production and pancreatic inflammation. We further show that NF-κB inhibitors could inhibit pre-diabetic cytokine production, β-cell damages and ameliorate the T1DM phenotype in SENP1-deficient mice. Feeding a high-fat diet augments both type-1 and type-2 diabetes phenotypes in SENP1-deficient mice, consistent with the effects on adipocyte-derived NF-κB and cytokine signalling. Our study reveals previously unrecognized mechanism regulating the onset and progression of T1DM associated with adipocyte dysfunction.

A comparison of linear and non-linear data assimilation methods using the NEMO ocean model

NASA Astrophysics Data System (ADS)

Kirchgessner, Paul; Tödter, Julian; Nerger, Lars

2015-04-01

The assimilation behavior of the widely used LETKF is compared with the Equivalent Weight Particle Filter (EWPF) in a data assimilation application with an idealized configuration of the NEMO ocean model. The experiments show how the different filter methods behave when they are applied to a realistic ocean test case. The LETKF is an ensemble-based Kalman filter, which assumes Gaussian error distributions and hence implicitly requires model linearity. In contrast, the EWPF is a fully nonlinear data assimilation method that does not rely on a particular error distribution. The EWPF has been demonstrated to work well in highly nonlinear situations, like in a model solving a barotropic vorticity equation, but it is still unknown how the assimilation performance compares to ensemble Kalman filters in realistic situations. For the experiments, twin assimilation experiments with a square basin configuration of the NEMO model are performed. The configuration simulates a double gyre, which exhibits significant nonlinearity. The LETKF and EWPF are both implemented in PDAF (Parallel Data Assimilation Framework, http://pdaf.awi.de), which ensures identical experimental conditions for both filters. To account for the nonlinearity, the assimilation skill of the two methods is assessed by using different statistical metrics, like CRPS and Histograms.

NEMO: Extraction and normalization of organization names from PubMed affiliations.

PubMed

Jonnalagadda, Siddhartha Reddy; Topham, Philip

2010-10-04

Today, there are more than 18 million articles related to biomedical research indexed in MEDLINE, and information derived from them could be used effectively to save the great amount of time and resources spent by government agencies in understanding the scientific landscape, including key opinion leaders and centers of excellence. Associating biomedical articles with organization names could significantly benefit the pharmaceutical marketing industry, health care funding agencies and public health officials and be useful for other scientists in normalizing author names, automatically creating citations, indexing articles and identifying potential resources or collaborators. Large amount of extracted information helps in disambiguating organization names using machine-learning algorithms. We propose NEMO, a system for extracting organization names in the affiliation and normalizing them to a canonical organization name. Our parsing process involves multi-layered rule matching with multiple dictionaries. The system achieves more than 98% f-score in extracting organization names. Our process of normalization that involves clustering based on local sequence alignment metrics and local learning based on finding connected components. A high precision was also observed in normalization. NEMO is the missing link in associating each biomedical paper and its authors to an organization name in its canonical form and the Geopolitical location of the organization. This research could potentially help in analyzing large social networks of organizations for landscaping a particular topic, improving performance of author disambiguation, adding weak links in the co-author network of authors, augmenting NLM's MARS system for correcting errors in OCR output of affiliation field, and automatically indexing the PubMed citations with the normalized organization name and country. Our system is available as a graphical user interface available for download along with this paper.

Feasibility Studies for a Mediterranean Neutrino Observatory - The NEMO.RD Project

NASA Astrophysics Data System (ADS)

de Marzo, C.; Ambriola, M.; Bellotti, R.; Cafagna, F.; Calicchio, M.; Ciacio, F.; Circella, M.; de Marzo, C.; Montaruli, T.; Falchieri, D.; Gabrielli, A.; Gandolfi, E.; Masetti, M.; Vitullo, C.; Zanarini, G.; Habel, R.; Usai, I.; Aiello, S.; Burrafato, G.; Caponetto, L.; Costanzo, E.; Lopresti, D.; Pappalardo, L.; Petta, C.; Randazzo, N.; Russo, G. V.; Troia, O.; Barnà, R.; D'Amico, V.; de Domenico, E.; de Pasquale, D.; Giacobbe, S.; Italiano, A.; Migliardo, F.; Salvato, G.; Trafirò, A.; Trimarchi, M.; Ameli, F.; Bonori, M.; Bottai, S.; Capone, A.; Desiati, P.; Massa, F.; Masullo, R.; Salusti, E.; Vicini, M.; Coniglione, R.; Migneco, E.; Piattelli, P.; Riccobene, R.; Sapienza, P.; Cordelli, M.; Trasatti, L.; Valente, V.; de Marchis, G.; Piccari, L.; Accerboni, E.; Mosetti, R.; Astraldi, M.; Gasparini, G. P.; Ulzega, A.; Orrù, P.

2000-06-01

The NEMO.RD Project is a feasibility study of a km3 underwater telescope for high energy astrophysical neutrinos to be located in the Mediterranea Sea. At present this study concerns: i) Monte Carlo simulation study of the capabilities of various arrays of phototubes in order to determine the detector geometry that can optimize performance and cost; ii) design of low power consumption electronic cards for data acquisition and transmission to shore; iii) feasibility study of mechanics, deployment, connection and maintenance of such a detector in collaboration with petrol industries having experience of undersea operations; iv) oceanographic exploration of various sites in search for the optimal one. A brief report on the status of points i) and iv) is presented here

Essential Oils and Their Components as Modulators of Antibiotic Activity against Gram-Negative Bacteria

PubMed Central

Aelenei, Petruta; Miron, Anca; Trifan, Adriana; Bujor, Alexandra; Gille, Elvira; Aprotosoaie, Ana Clara

2016-01-01

Gram-negative bacteria cause infections that are difficult to treat due to the emergence of multidrug resistance. This review summarizes the current status of the studies investigating the capacity of essential oils and their components to modulate antibiotic activity against Gram-negative bacteria. Synergistic interactions are particularly discussed with reference to possible mechanisms by which essential oil constituents interact with antibiotics. Special emphasis is given to essential oils and volatile compounds that inhibit efflux pumps, thus reversing drug resistance in Gram-negative bacteria. In addition, indifference and antagonism between essential oils/volatile compounds and conventional antibiotics have also been reported. Overall, this literature review reveals that essential oils and their purified components enhance the efficacy of antibiotics against Gram-negative bacteria, being promising candidates for the development of new effective formulations against Gram-negative bacteria. PMID:28930130

Nemo-like kinase (NLK) expression in osteoblastic cells and suppression of osteoblastic differentiation

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

Nifuji, Akira, E-mail: nifuji-a@tsurumi-u.ac.jp; Department of Pharmacology, Tsurumi University School of Dental Medicine, Yokohama; Ideno, Hisashi

2010-04-15

Mitogen-activated protein kinases (MAPKs) regulate proliferation and differentiation in osteoblasts. The vertebral homologue of nemo, nemo-like kinase (NLK), is an atypical MAPK that targets several signaling components, including the T-cell factor/lymphoid enhancer factor (TCF/Lef1) transcription factor. Recent studies have shown that NLK forms a complex with the histone H3-K9 methyltransferase SETDB1 and suppresses peroxisome proliferator-activated receptor (PPAR)-gamma:: action in the mesenchymal cell line ST2. Here we investigated whether NLK regulates osteoblastic differentiation. We showed that NLK mRNA is expressed in vivo in osteoblasts at embryonic day 18.5 (E18.5) mouse calvariae. By using retrovirus vectors, we performed forced expression of NLKmore » in primary calvarial osteoblasts (pOB cells) and the mesenchymal cell line ST2. Wild-type NLK (NLK-WT) suppressed alkaline phosphatase activity and expression of bone marker genes such as alkaline phosphatase, type I procollagen, runx2, osterix, steopontin and osteocalcin in these cells. NLK-WT also decreased type I collagen protein expression in pOB and ST2 cells. Furthermore, mineralized nodule formation was reduced in pOB cells overexpressing NLK-WT. In contrast, kinase-negative form of NLK (NLK-KN) did not suppress or partially suppress ALP activity and bone marker gene expression in pOB and ST2 cells. NLK-KN did not suppress nodule formation in pOB cells. In addition to forced expression, suppression of endogenous NLK expression by siRNA increased bone marker gene expression in pOB and ST2 cells. Finally, transcriptional activity analysis of gene promoters revealed that NLK-WT suppressed Wnt1 activation of TOP flash promoter and Runx2 activation of the osteocalcin promoter. Taken together, these results suggest that NLK negatively regulates osteoblastic differentiation.« less

NBodyLab: A Testbed for Undergraduates Utilizing a Web Interface to NEMO and MD-GRAPE2 Hardware

NASA Astrophysics Data System (ADS)

Johnson, V. L.; Teuben, P. J.; Penprase, B. E.

An N-body simulation testbed called NBodyLab was developed at Pomona College as a teaching tool for undergraduates. The testbed runs under Linux and provides a web interface to selected back-end NEMO modeling and analysis tools, and several integration methods which can optionally use an MD-GRAPE2 supercomputer card in the server to accelerate calculation of particle-particle forces. The testbed provides a framework for using and experimenting with the main components of N-body simulations: data models and transformations, numerical integration of the equations of motion, analysis and visualization products, and acceleration techniques (in this case, special purpose hardware). The testbed can be used by students with no knowledge of programming or Unix, freeing such students and their instructor to spend more time on scientific experimentation. The advanced student can extend the testbed software and/or more quickly transition to the use of more advanced Unix-based toolsets such as NEMO, Starlab and model builders such as GalactICS. Cosmology students at Pomona College used the testbed to study collisions of galaxies with different speeds, masses, densities, collision angles, angular momentum, etc., attempting to simulate, for example, the Tadpole Galaxy and the Antenna Galaxies. The testbed framework is available as open-source to assist other researchers and educators. Recommendations are made for testbed enhancements.

Measurement of the BB Decay Half-Life of 130Te with the NEMO-3 Detector

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

A. J. Caffrey

2011-08-01

We report results from the NEMO-3 experiment based on an exposure of 1275 days with 661 g of 130Te in the form of enriched and natural tellurium foils. The double B decay rate of 130Te is found to be greater than zero with a significance of 7.7 standard deviations and the half-life is measured to be T2v 1/2 = [7.0 +/- 0.9(stat) +/- 1.1 (syst)] x 10{sup 20} yr. This represents the most precise measurement of this half-life yet published and the first real-time observation of this decay.

Auditory “bubbles”: Efficient classification of the spectrotemporal modulations essential for speech intelligibility

PubMed Central

Venezia, Jonathan H.; Hickok, Gregory; Richards, Virginia M.

2016-01-01

Speech intelligibility depends on the integrity of spectrotemporal patterns in the signal. The current study is concerned with the speech modulation power spectrum (MPS), which is a two-dimensional representation of energy at different combinations of temporal and spectral (i.e., spectrotemporal) modulation rates. A psychophysical procedure was developed to identify the regions of the MPS that contribute to successful reception of auditory sentences. The procedure, based on the two-dimensional image classification technique known as “bubbles” (Gosselin and Schyns (2001). Vision Res. 41, 2261–2271), involves filtering (i.e., degrading) the speech signal by removing parts of the MPS at random, and relating filter patterns to observer performance (keywords identified) over a number of trials. The result is a classification image (CImg) or “perceptual map” that emphasizes regions of the MPS essential for speech intelligibility. This procedure was tested using normal-rate and 2×-time-compressed sentences. The results indicated: (a) CImgs could be reliably estimated in individual listeners in relatively few trials, (b) CImgs tracked changes in spectrotemporal modulation energy induced by time compression, though not completely, indicating that “perceptual maps” deviated from physical stimulus energy, and (c) the bubbles method captured variance in intelligibility not reflected in a common modulation-based intelligibility metric (spectrotemporal modulation index or STMI). PMID:27586738

CIKS, a connection to IκB kinase and stress-activated protein kinase

PubMed Central

Leonardi, Antonio; Chariot, Alain; Claudio, Estefania; Cunningham, Kirk; Siebenlist, Ulrich

2000-01-01

Pathogens, inflammatory signals, and stress cause acute transcriptional responses in cells. The induced expression of genes in response to these signals invariably involves transcription factors of the NF-κB and AP-1/ATF families. Activation of NF-κB factors is thought to be mediated primarily via IκB kinases (IKK), whereas that of AP-1/ATF can be mediated by stress-activated protein kinases (SAPKs; also named Jun kinases or JNKs). IKKα and IKKβ are two catalytic subunits of a core IKK complex that also contains the regulatory subunit NEMO (NF-κB essential modulator)/IKKγ. The latter protein is essential for activation of the IKKs, but its mechanism of action is not known. Here we describe the molecular cloning of CIKS (connection to IKK and SAPK/JNK), a previously unknown protein that directly interacts with NEMO/IKKγ in cells. When ectopically expressed, CIKS stimulates IKK and SAPK/JNK kinases and it transactivates an NF-κB-dependent reporter. Activation of NF-κB is prevented in the presence of kinase-deficient, interfering mutants of the IKKs. CIKS may help to connect upstream signaling events to IKK and SAPK/JNK modules. CIKS could coordinate the activation of two stress-induced signaling pathways, functions reminiscent of those noted for tumor necrosis factor receptor-associated factor adaptor proteins. PMID:10962033

CIKS, a connection to Ikappa B kinase and stress-activated protein kinase.

PubMed

Leonardi, A; Chariot, A; Claudio, E; Cunningham, K; Siebenlist, U

2000-09-12

Pathogens, inflammatory signals, and stress cause acute transcriptional responses in cells. The induced expression of genes in response to these signals invariably involves transcription factors of the NF-kappaB and AP-1/ATF families. Activation of NF-kappaB factors is thought to be mediated primarily via IkappaB kinases (IKK), whereas that of AP-1/ATF can be mediated by stress-activated protein kinases (SAPKs; also named Jun kinases or JNKs). IKKalpha and IKKbeta are two catalytic subunits of a core IKK complex that also contains the regulatory subunit NEMO (NF-kappaB essential modulator)/IKKgamma. The latter protein is essential for activation of the IKKs, but its mechanism of action is not known. Here we describe the molecular cloning of CIKS (connection to IKK and SAPK/JNK), a previously unknown protein that directly interacts with NEMO/IKKgamma in cells. When ectopically expressed, CIKS stimulates IKK and SAPK/JNK kinases and it transactivates an NF-kappaB-dependent reporter. Activation of NF-kappaB is prevented in the presence of kinase-deficient, interfering mutants of the IKKs. CIKS may help to connect upstream signaling events to IKK and SAPK/JNK modules. CIKS could coordinate the activation of two stress-induced signaling pathways, functions reminiscent of those noted for tumor necrosis factor receptor-associated factor adaptor proteins.

GAP-43 is essential for the neurotrophic effects of BDNF and positive AMPA receptor modulator S18986.

PubMed

Gupta, S K; Mishra, R; Kusum, S; Spedding, M; Meiri, K F; Gressens, P; Mani, S

2009-04-01

Positive alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor modulators include benzamide compounds that allosterically modulate AMPA glutamate receptors. These small molecules that cross the blood-brain barrier have been shown to act as a neuroprotectant by increasing the levels of endogenous brain-derived neurotrophic factor (BDNF). Positive AMPA receptor modulators have also been shown to increase the levels of growth-associated protein-43 (GAP-43). GAP-43 plays a major role in many aspects of neuronal function in vertebrates. The goal of this study was to determine whether GAP-43 was important in mediating the actions of positive AMPA receptor modulator (S18986) and BDNF. Using cortical cultures from GAP-43 knockout and control mice, we show that (1) GAP-43 is upregulated in response to S18986 and BDNF in control cultures; (2) this upregulation of GAP-43 is essential for mediating the neuroprotective effects of S18986 and BDNF; (3) administration of S18986 and BDNF leads to an increase in the expression of the glutamate transporters GLT-1 and GLAST that are key to limiting excitotoxic cell death and this increase in GLT-1 and GLAST expression is completely blocked in the absence of GAP-43. Taken together this study concludes that GAP-43 is an important mediator of the neurotrophic effects of S18986 and BDNF on neuronal survival and plasticity, and is essential for the success of positive AMPA receptor modulator-BDNF-based neurotrophin therapy.

MINE: Module Identification in Networks

PubMed Central

2011-01-01

Background Graphical models of network associations are useful for both visualizing and integrating multiple types of association data. Identifying modules, or groups of functionally related gene products, is an important challenge in analyzing biological networks. However, existing tools to identify modules are insufficient when applied to dense networks of experimentally derived interaction data. To address this problem, we have developed an agglomerative clustering method that is able to identify highly modular sets of gene products within highly interconnected molecular interaction networks. Results MINE outperforms MCODE, CFinder, NEMO, SPICi, and MCL in identifying non-exclusive, high modularity clusters when applied to the C. elegans protein-protein interaction network. The algorithm generally achieves superior geometric accuracy and modularity for annotated functional categories. In comparison with the most closely related algorithm, MCODE, the top clusters identified by MINE are consistently of higher density and MINE is less likely to designate overlapping modules as a single unit. MINE offers a high level of granularity with a small number of adjustable parameters, enabling users to fine-tune cluster results for input networks with differing topological properties. Conclusions MINE was created in response to the challenge of discovering high quality modules of gene products within highly interconnected biological networks. The algorithm allows a high degree of flexibility and user-customisation of results with few adjustable parameters. MINE outperforms several popular clustering algorithms in identifying modules with high modularity and obtains good overall recall and precision of functional annotations in protein-protein interaction networks from both S. cerevisiae and C. elegans. PMID:21605434

Finding NEMO (novel electromaterial muscle oscillator): a polypyrrole powered robotic fish with real-time wireless speed and directional control

NASA Astrophysics Data System (ADS)

McGovern, Scott; Alici, Gursel; Truong, Van-Tan; Spinks, Geoffrey

2009-09-01

This paper presents the development of an autonomously powered and controlled robotic fish that incorporates an active flexural joint tail fin, activated through conducting polymer actuators based on polypyrrole (PPy). The novel electromaterial muscle oscillator (NEMO) tail fin assembly on the fish could be controlled wirelessly in real time by varying the frequency and duty cycle of the voltage signal supplied to the PPy bending-type actuators. Directional control was achieved by altering the duty cycle of the voltage input to the NEMO tail fin, which shifted the axis of oscillation and enabled turning of the robotic fish. At low speeds, the robotic fish had a turning circle as small as 15 cm (or 1.1 body lengths) in radius. The highest speed of the fish robot was estimated to be approximately 33 mm s-1 (or 0.25 body lengths s-1) and was achieved with a flapping frequency of 0.6-0.8 Hz which also corresponded with the most hydrodynamically efficient mode for tail fin operation. This speed is approximately ten times faster than those for any previously reported artificial muscle based device that also offers real-time speed and directional control. This study contributes to previously published studies on bio-inspired functional devices, demonstrating that electroactive polymer actuators can be real alternatives to conventional means of actuation such as electric motors.

Hypohidrotic ectodermal dysplasia, osteopetrosis, lymphedema, and immunodeficiency in an infant with multiple opportunistic infections.

PubMed

Carlberg, Valerie M; Lofgren, Sabra M; Mann, Julianne A; Austin, Jared P; Nolt, Dawn; Shereck, Evan B; Davila-Saldana, Blachy; Zonana, Jonathan; Krol, Alfons L

2014-01-01

Osteopetrosis, lymphedema, hypohidrotic ectodermal dysplasia, and immunodeficiency (OL-HED-ID) is a rare X-linked disorder with only three reported prior cases in the English-language literature. We describe a case of OL-HED-ID in a male infant who initially presented with congenital lymphedema, leukocytosis, and thrombocytopenia of unknown etiology at 7 days of age. He subsequently developed gram-negative sepsis and multiple opportunistic infections including high-level cytomegalovirus viremia and Pneumocystis jiroveci pneumonia. The infant was noted to have mildly xerotic skin, fine sparse hair, and periorbital wrinkling, all features suggestive of ectodermal dysplasia. Skeletal imaging showed findings consistent with osteopetrosis, and immunologic investigation revealed hypogammaglobulinemia and mixed T- and B-cell dysfunction. Genetic testing revealed a novel mutation in the nuclear factor kappa beta (NF-KB) essential modulator (NEMO) gene, confirming the diagnosis of OL-HED-ID. Mutations in the NEMO gene have been reported in association with hypohidrotic ectodermal dysplasia with immunodeficiency (HED-ID), OL-HED-ID, and incontinentia pigmenti. In this case, we report a novel mutation in the NEMO gene associated with OL-HED-ID. This article highlights the dermatologic manifestations of a rare disorder, OL-HED-ID, and underscores the importance of early recognition and prompt intervention to prevent life-threatening infections. © 2013 Wiley Periodicals, Inc.

Chemical composition and modulation of bacterial drug resistance of the essential oil from leaves of Croton grewioides.

PubMed

de Medeiros, Vivianne Marcelino; do Nascimento, Yuri Mangueira; Souto, Augusto Lopes; Madeiro, Sara Alves Lucena; Costa, Vicente Carlos de Oliveira; Silva, Suellen Maria P M; Falcão Silva, Vivyanne Dos Santos; Agra, Maria de Fátima; de Siqueira-Júnior, José Pinto; Tavares, Josean Fechine

2017-10-01

The essential oil from leaves of Croton grewioides Baill was obtained by hydrodistillation using Clevenger apparatus, and its chemical composition was analyzed by GC-MS, where 18 compounds were identified, mostly as monoterpenes (55.56%) and sesquiterpenes (44.44%), in which the major constituent was the α-pinene (47.43%). The essential oil of Croton grewioides (EOCg) and its major compound (α-pinene) were evaluated as modulators of antibiotic resistance in strain SA-1199B and IS-58 of Staphylococcus aureus that overexpresses efflux protein. The minimum inhibitory concentrations (MICs) of the antibiotics were determined by the microdilution assay in the absence and in the presence of sub-inhibitory concentration of EOCg and α-pinene. Although the EOCg and α-pinene did not indicate relevant antibacterial activity in vitro, they acted as antibiotic resistance modulators, i.e., EOCg in combination with norfloxacin, reducted its MIC, by 64× whereas in combination with tetracycline it was observed a reduction of 4×. Additionally, it was observed a MIC reduction of tetracycline by 32×, when combined with α-pinene. The results suggest that EOCg and α-pinene modulate or even reverse bacterial resistance as a putative efflux pump inhibitor. Copyright © 2017 Elsevier Ltd. All rights reserved.

Radon emanation based material measurement and selection for the SuperNEMO double beta experiment

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

Cerna, Cédric, E-mail: cerna@cenbg.in2p3.fr; Soulé, Benjamin; Perrot, Frédéric

The SuperNEMO Demonstrator experiment aims to study the neutrinoless double beta decay of 7 kg of {sup 82}Se in order to reach a limit on the light Majorana neutrino mass mechanism T{sub 1/2} (ββ0ν) > 6.5 10{sup 24} years (90%CL) equivalent to a mass sensitivity mβ{sub β} < 0.20 - 0.40 eV (90%CL) in two years of data taking. The detector construction started in 2014 and its installation in the Laboratoire Souterrain de Modane (LSM) is expected during the course of 2015. The remaining level of {sup 226}Ra ({sup 238}U chain) in the detector components can lead to the emanationmore » of {sup 222}Rn gas. This isotope should be controlled and reduced down to the level of a 150 µBq/m{sup 3} in the tracker chamber of the detector to achieve the physics goals. Besides the HPGe selection of the detector materials for their radiopurity, the most critical materials have been tested and selected in a dedicated setup facility able to measure their {sup 222}Rn emanation level. The operating principle relies on a large emanation tank (0.7m{sup 3}) that allows measuring large material surfaces or large number of construction pieces. The emanation tank is coupled to an electrostatic detector equipped with a silicon diode to perform the alpha spectroscopy of the gas it contains and extract the {sup 222}Rn daughters. The transfer efficiency and the detector efficiency have been carefully calibrated through different methods. The intrinsic background of the system allows one to measure 222Rn activities down to 3 mBq, leading to a typical emanation sensitivity of 20 µBq/m{sup 2}/day for a 30 m{sup 2} surface sample. Several construction materials have been measured and selected, such as nylon and aluminized Mylar films, photomultipliers and tracking of the SuperNEMO Demonstrator.« less

2013 Mt. Etna Pyroclastic Activity through the ADCP Recordings of NEMO-SN1 Multidisciplinary Seafloor Observatory

NASA Astrophysics Data System (ADS)

Lo Bue, N.; Sgroi, T.; Giovinetti, G.; Marinaro, G.; Favali, P.

2014-12-01

The Acoustic Doppler Current Profiler (ADCP) is one of the most useful sensor used to measure speed and direction of sea currents in the water column. More often ADCPs are being also used to monitor concentration of suspended matter in rivers or in marine environments by the analysis of the acoustic backscatter intensity. In the framework of the European Research Infrastructure EMSO (European Multidisciplinary Seafloor and water-column Observatory, www.emso-eu.org), its cabled node, the NEMO-SN1 multidisciplinary seafloor observatory, was deployed in the Western Ionian Sea (Southern Italy) at a depth of 2100 m, about 25 km off-shore Eastern Sicily close to the submarine slope of the Mt. Etna volcano. Starting from February 2013, the Mt. Etna was interested by thirteen different parossistic events producing intense eruption followed by pyroclastic fallout that reached distances of tens kilometres from the eruptive centre. Four of these events affected the ESE sector with a consequent fallout in the Western Ionian Sea and they were detected by NEMO-SN1. In fact, its scientific payload also included an ADCP (RDI WorkHorse 600 kHz) with the main aim to monitor the hydrodynamic conditions of about 30 metres of the water column above the station. Surprisingly, this sensor offered spectacular recordings of the Mt. Etna pyroclastic activity occurred on 2013 wich affected the ESE sector. This work aims to present new records of pyroclastic fallout associated to explosive events observed at sea bottom by the analysis of backscatter signal of the ADCP. A multidisciplinary approach taking into account the Mt. Etna eruptive activity as well as the local oceanographic dynamic is necessary to describe marine processes involved in volcanic ash sedimentation.

Search for Neutrinoless Quadruple-β Decay of Nd 150 with the NEMO-3 Detector

NASA Astrophysics Data System (ADS)

Arnold, R.; Augier, C.; Barabash, A. S.; Basharina-Freshville, A.; Blondel, S.; Blot, S.; Bongrand, M.; Boursette, D.; Brudanin, V.; Busto, J.; Caffrey, A. J.; Calvez, S.; Cascella, M.; Cerna, C.; Cesar, J. P.; Chapon, A.; Chauveau, E.; Chopra, A.; Dawson, L.; Duchesneau, D.; Durand, D.; Egorov, V.; Eurin, G.; Evans, J. J.; Fajt, L.; Filosofov, D.; Flack, R.; Garrido, X.; Gómez, H.; Guillon, B.; Guzowski, P.; Hodák, R.; Huber, A.; Hubert, P.; Hugon, C.; Jullian, S.; Klimenko, A.; Kochetov, O.; Konovalov, S. I.; Kovalenko, V.; Lalanne, D.; Lang, K.; Lemière, Y.; Le Noblet, T.; Liptak, Z.; Liu, X. R.; Loaiza, P.; Lutter, G.; Macko, M.; Macolino, C.; Mamedov, F.; Marquet, C.; Mauger, F.; Morgan, B.; Mott, J.; Nemchenok, I.; Nomachi, M.; Nova, F.; Nowacki, F.; Ohsumi, H.; Patrick, C.; Pahlka, R. B.; Perrot, F.; Piquemal, F.; Povinec, P.; Přidal, P.; Ramachers, Y. A.; Remoto, A.; Reyss, J. L.; Riddle, C. L.; Rukhadze, E.; Saakyan, R.; Salazar, R.; Sarazin, X.; Shitov, Yu.; Simard, L.; Šimkovic, F.; Smetana, A.; Smolek, K.; Smolnikov, A.; Söldner-Rembold, S.; Soulé, B.; Štefánik, D.; Štekl, I.; Suhonen, J.; Sutton, C. S.; Szklarz, G.; Thomas, J.; Timkin, V.; Torre, S.; Tretyak, Vl. I.; Tretyak, V. I.; Umatov, V. I.; Vanushin, I.; Vilela, C.; Vorobel, V.; Waters, D.; Xie, F.; Žukauskas, A.; NEMO-3 Collaboration

2017-07-01

We report the results of a first experimental search for lepton number violation by four units in the neutrinoless quadruple-β decay of Nd 150 using a total exposure of 0.19 kg yr recorded with the NEMO-3 detector at the Modane Underground Laboratory. We find no evidence of this decay and set lower limits on the half-life in the range T1 /2>(1.1 - 3.2 )×1 021 yr at the 90% C.L., depending on the model used for the kinematic distributions of the emitted electrons.

Toxic essential oils. Part V: Behaviour modulating and toxic properties of thujones and thujone-containing essential oils of Salvia officinalis L., Artemisia absinthium L., Thuja occidentalis L. and Tanacetum vulgare L.

PubMed

Radulović, Niko S; Genčić, Marija S; Stojanović, Nikola M; Randjelović, Pavle J; Stojanović-Radić, Zorica Z; Stojiljković, Nenad I

2017-07-01

Neurotoxic thujones (α- and β-diastereoisomers) are common constituents of plant essential oils. In this study, we employed a statistical approach to determine the contribution of thujones to the overall observed behaviour-modulating and toxic effects of essential oils (Salvia officinalis L., Artemisia absinthium L., Thuja occidentalis L. and Tanacetum vulgare L.) containing these monoterpene ketones. The data from three in vivo neuropharmacological tests on rats (open field, light-dark, and diazepam-induced sleep), and toxicity assays (brine shrimp, and antimicrobial activity against a panel of microorganisms), together with the data from detailed chemical analyses, were subjected to a multivariate statistical treatment to reveal the possible correlation(s) between the content of essential-oil constituents and the observed effects. The results strongly imply that the toxic and behaviour-modulating activity of the oils (hundreds of constituents) should not be associated exclusively with thujones. The statistical analyses pinpointed to a number of essential-oil constituents other than thujones that demonstrated a clear correlation with either the toxicity, antimicrobial effect or the activity on CNS. Thus, in addition to the thujone content, the amount and toxicity of other constituents should be taken into consideration when making risk assessment and determining the regulatory status of plants in food and medicines. Copyright © 2017 Elsevier Ltd. All rights reserved.

Study of water masses variability in the Mediterranean Sea using in-situ data / NEMO-Med12 model.

NASA Astrophysics Data System (ADS)

Margirier, Félix; Testor, Pierre; Mortier, Laurent; Arsouze, Thomas; Bosse, Anthony; Houpert, Loic; Hayes, Dan

2016-04-01

In the past 10 years, numerous observation programs in the Mediterranean deployed autonomous platforms (moorings, argo floats, gliders) and thus considerably increased the number of in-situ observations and the data coverage. In this study, we analyse time series built with profile data on interannual scales. Sorting data in regional boxes, we follow the evolution of different water masses in the basin and generate indexes to characterize their evolution. We then put those indexes in relation with external (atmospheric) forcings and present an intercomparison with the NEMO-Med12 model to estimate both the skill of the model and the relevance of the data-sampling in reproducing the evolution of water masses properties.

Phosphorylation and ubiquitination of the IkappaB kinase complex by two distinct signaling pathways.

PubMed

Shambharkar, Prashant B; Blonska, Marzenna; Pappu, Bhanu P; Li, Hongxiu; You, Yun; Sakurai, Hiroaki; Darnay, Bryant G; Hara, Hiromitsu; Penninger, Josef; Lin, Xin

2007-04-04

The IkappaB kinase (IKK) complex serves as the master regulator for the activation of NF-kappaB by various stimuli. It contains two catalytic subunits, IKKalpha and IKKbeta, and a regulatory subunit, IKKgamma/NEMO. The activation of IKK complex is dependent on the phosphorylation of IKKalpha/beta at its activation loop and the K63-linked ubiquitination of NEMO. However, the molecular mechanism by which these inducible modifications occur remains undefined. Here, we demonstrate that CARMA1, a key scaffold molecule, is essential to regulate NEMO ubiquitination upon T-cell receptor (TCR) stimulation. However, the phosphorylation of IKKalpha/beta activation loop is independent of CARMA1 or NEMO ubiquitination. Further, we provide evidence that TAK1 is activated and recruited to the synapses in a CARMA1-independent manner and mediate IKKalpha/beta phosphorylation. Thus, our study provides the biochemical and genetic evidence that phosphorylation of IKKalpha/beta and ubiquitination of NEMO are regulated by two distinct pathways upon TCR stimulation.

Phase dependent modulation of tremor amplitude in essential tremor through thalamic stimulation

PubMed Central

Cagnan, Hayriye; Brittain, John-Stuart; Little, Simon; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Joint, Carole; Fitzgerald, James; Green, Alexander L.; Aziz, Tipu

2013-01-01

High frequency deep brain stimulation of the thalamus can help ameliorate severe essential tremor. Here we explore how the efficacy, efficiency and selectivity of thalamic deep brain stimulation might be improved in this condition. We started from the hypothesis that the effects of electrical stimulation on essential tremor may be phase dependent, and that, in particular, there are tremor phases at which stimuli preferentially lead to a reduction in the amplitude of tremor. The latter could be exploited to improve deep brain stimulation, particularly if tremor suppression could be reinforced by cumulative effects. Accordingly, we stimulated 10 patients with essential tremor and thalamic electrodes, while recording tremor amplitude and phase. Stimulation near the postural tremor frequency entrained tremor. Tremor amplitude was also modulated depending on the phase at which stimulation pulses were delivered in the tremor cycle. Stimuli in one half of the tremor cycle reduced median tremor amplitude by ∼10%, while those in the opposite half of the tremor cycle increased tremor amplitude by a similar amount. At optimal phase alignment tremor suppression reached 27%. Moreover, tremor amplitude showed a non-linear increase in the degree of suppression with successive stimuli; tremor suppression was increased threefold if a stimulus was preceded by four stimuli with a similar phase relationship with respect to the tremor, suggesting cumulative, possibly plastic, effects. The present results pave the way for a stimulation system that tracks tremor phase to control when deep brain stimulation pulses are delivered to treat essential tremor. This would allow treatment effects to be maximized by focussing stimulation on the optimal phase for suppression and by ensuring that this is repeated over many cycles so as to harness cumulative effects. Such a system might potentially achieve tremor control with far less power demand and greater specificity than current high frequency

Scaling and stochastic cascade properties of NEMO oceanic simulations and their potential value for GCM evaluation and downscaling

NASA Astrophysics Data System (ADS)

Verrier, Sébastien; Crépon, Michel; Thiria, Sylvie

2014-09-01

Spectral scaling properties have already been evidenced on oceanic numerical simulations and have been subject to several interpretations. They can be used to evaluate classical turbulence theories that predict scaling with specific exponents and to evaluate the quality of GCM outputs from a statistical and multiscale point of view. However, a more complete framework based on multifractal cascades is able to generalize the classical but restrictive second-order spectral framework to other moment orders, providing an accurate description of probability distributions of the fields at multiple scales. The predictions of this formalism still needed systematic verification in oceanic GCM while they have been confirmed recently for their atmospheric counterparts by several papers. The present paper is devoted to a systematic analysis of several oceanic fields produced by the NEMO oceanic GCM. Attention is focused to regional, idealized configurations that permit to evaluate the NEMO engine core from a scaling point of view regardless of limitations involved by land masks. Based on classical multifractal analysis tools, multifractal properties were evidenced for several oceanic state variables (sea surface temperature and salinity, velocity components, etc.). While first-order structure functions estimated a different nonconservativity parameter H in two scaling ranges, the multiorder statistics of turbulent fluxes were scaling over almost the whole available scaling range. This multifractal scaling was then parameterized with the help of the universal multifractal framework, providing parameters that are coherent with existing empirical literature. Finally, we argue that the knowledge of these properties may be useful for oceanographers. The framework seems very well suited for the statistical evaluation of OGCM outputs. Moreover, it also provides practical solutions to simulate subpixel variability stochastically for GCM downscaling purposes. As an independent

Comparative study of sea ice dynamics simulations with a Maxwell elasto-brittle rheology and the elastic-viscous-plastic rheology in NEMO-LIM3

NASA Astrophysics Data System (ADS)

Raulier, Jonathan; Dansereau, Véronique; Fichefet, Thierry; Legat, Vincent; Weiss, Jérôme

2017-04-01

Sea ice is a highly dynamical environment characterized by a dense mesh of fractures or leads, constantly opening and closing over short time scales. This characteristic geomorphology is linked to the existence of linear kinematic features, which consist of quasi-linear patterns emerging from the observed strain rate field of sea ice. Standard rheologies used in most state-of-the-art sea ice models, like the well-known elastic-viscous-plastic rheology, are thought to misrepresent those linear kinematic features and the observed statistical distribution of deformation rates. Dedicated rheologies built to catch the processes known to be at the origin of the formation of leads are developed but still need evaluations on the global scale. One of them, based on a Maxwell elasto-brittle formulation, is being integrated in the NEMO-LIM3 global ocean-sea ice model (www.nemo-ocean.eu; www.elic.ucl.ac.be/lim). In the present study, we compare the results of the sea ice model LIM3 obtained with two different rheologies: the elastic-viscous-plastic rheology commonly used in LIM3 and a Maxwell elasto-brittle rheology. This comparison is focused on the statistical characteristics of the simulated deformation rate and on the ability of the model to reproduce the existence of leads within the ice pack. The impact of the lead representation on fluxes between ice, atmosphere and ocean is also assessed.

Antimicrobial and Virulence-Modulating Effects of Clove Essential Oil on the Foodborne Pathogen Campylobacter jejuni

PubMed Central

Kovács, Judit K.; Felső, Péter; Makszin, Lilla; Pápai, Zoltán; Horváth, Györgyi; Ábrahám, Hajnalka; Palkovics, Tamás; Böszörményi, Andrea; Emődy, Levente

2016-01-01

ABSTRACT Our study investigated the antimicrobial action of clove (Syzygium aromaticum) essential oil (EO) on the zoonotic pathogen Campylobacter jejuni. After confirming the clove essential oil's general antibacterial effect, we analyzed the reference strain Campylobacter jejuni NCTC 11168. Phenotypic, proteomic, and transcriptomic methods were used to reveal changes in cell morphology and functions when exposed to sublethal concentrations of clove EO. The normally curved cells showed markedly straightened and shrunken morphology on the scanning electron micrographs as a result of stress. Although, oxidative stress, as a generally accepted response to essential oils, was also present, the dominance of a general stress response was demonstrated by reverse transcription-PCR (RT-PCR). The results of RT-PCR and two-dimensional (2D) PAGE revealed that clove oil perturbs the expression of virulence-associated genes taking part in the synthesis of flagella, PEB1, PEB4, lipopolysaccharide (LPS), and serine protease. Loss of motility was also detected by a phenotypic test. Bioautographic analysis revealed that besides its major component, eugenol, at least four other spots of clove EO possessed bactericidal activity against C. jejuni. Our findings show that clove EO has a marked antibacterial and potential virulence-modulating effect on C. jejuni. IMPORTANCE This study demonstrates that the components of clove essential oil influence not only the expression of general stress genes but also the expression of virulence-associated genes. Based on this finding, alternative strategies can be worked on to control this important foodborne pathogen. PMID:27520816

"S.P.E.R.M." (seminal proteins (are) essential reproductive modulators): the view from Drosophila.

PubMed

Wolfner, M F

2007-01-01

The seminal fluid that females receive from their mates contains a suite of proteins that have important effects on sperm, as well as on reproduction in general. Seminal proteins are vital for the fertility of mating animals in several diverse taxonomic groups. For example, in Drosophila melanogaster, the approximately 70-106 accessory gland proteins (Acps) that are a major part of the seminal fluid are essential for the storage and utilization of sperm, as well as for increasing egg production and laying by the female. In addition, Acps have been implicated in modifying the female's eating behaviour, her receptivity to re-mating and her longevity. This review will first summarise the molecular nature and reproductive function of Drosophila Acps in general, as elucidated by genetic/ transgenesis, biochemical, and physiological experiments. The article will then focus on Acps that affect, or interact with, sperm. Sperm storage is a stepwise process in Drosophila and Acps facilitate at least some of these steps. For example, Acps promote sperm entry into storage, apparently by modulating muscle contractions in the female's reproductive tract. One Acp is known to be essential for the entry of sperm into storage. This Acp, which is cleaved after entering females, binds to sperm and enters the sperm-storage organs. Egg production, which is also modulated by Acps, can affect the transition between the steps in sperm storage, although not the rate of release of sperm from storage. Results on additional roles of Acp-sperm interaction in Drosophila will be reviewed.

Antimicrobial and Virulence-Modulating Effects of Clove Essential Oil on the Foodborne Pathogen Campylobacter jejuni.

PubMed

Kovács, Judit K; Felső, Péter; Makszin, Lilla; Pápai, Zoltán; Horváth, Györgyi; Ábrahám, Hajnalka; Palkovics, Tamás; Böszörményi, Andrea; Emődy, Levente; Schneider, György

2016-10-15

Our study investigated the antimicrobial action of clove (Syzygium aromaticum) essential oil (EO) on the zoonotic pathogen Campylobacter jejuni After confirming the clove essential oil's general antibacterial effect, we analyzed the reference strain Campylobacter jejuni NCTC 11168. Phenotypic, proteomic, and transcriptomic methods were used to reveal changes in cell morphology and functions when exposed to sublethal concentrations of clove EO. The normally curved cells showed markedly straightened and shrunken morphology on the scanning electron micrographs as a result of stress. Although, oxidative stress, as a generally accepted response to essential oils, was also present, the dominance of a general stress response was demonstrated by reverse transcription-PCR (RT-PCR). The results of RT-PCR and two-dimensional (2D) PAGE revealed that clove oil perturbs the expression of virulence-associated genes taking part in the synthesis of flagella, PEB1, PEB4, lipopolysaccharide (LPS), and serine protease. Loss of motility was also detected by a phenotypic test. Bioautographic analysis revealed that besides its major component, eugenol, at least four other spots of clove EO possessed bactericidal activity against C. jejuni Our findings show that clove EO has a marked antibacterial and potential virulence-modulating effect on C. jejuni IMPORTANCE: This study demonstrates that the components of clove essential oil influence not only the expression of general stress genes but also the expression of virulence-associated genes. Based on this finding, alternative strategies can be worked on to control this important foodborne pathogen. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

A parapoxviral virion protein inhibits NF-κB signaling early in infection

PubMed Central

Khatiwada, Sushil; Delhon, Gustavo; Nagendraprabhu, Ponnuraj; Chaulagain, Sabal; Luo, Shuhong; Diel, Diego G.; Flores, Eduardo F.

2017-01-01

Poxviruses have evolved unique proteins and mechanisms to counteract the nuclear factor κB (NF-κB) signaling pathway, which is an essential regulatory pathway of host innate immune responses. Here, we describe a NF-κB inhibitory virion protein of orf virus (ORFV), ORFV073, which functions very early in infected cells. Infection with ORFV073 gene deletion virus (OV-IA82Δ073) led to increased accumulation of NF-κB essential modulator (NEMO), marked phosphorylation of IκB kinase (IKK) subunits IKKα and IKKβ, IκBα and NF-κB subunit p65 (NF-κB-p65), and to early nuclear translocation of NF-κB-p65 in virus-infected cells (≤ 30 min post infection). Expression of ORFV073 alone was sufficient to inhibit TNFα induced activation of the NF-κB signaling in uninfected cells. Consistent with observed inhibition of IKK complex activation, ORFV073 interacted with the regulatory subunit of the IKK complex NEMO. Infection of sheep with OV-IA82Δ073 led to virus attenuation, indicating that ORFV073 is a virulence determinant in the natural host. Notably, ORFV073 represents the first poxviral virion-associated NF-κB inhibitor described, highlighting the significance of viral inhibition of NF-κB signaling very early in infection. PMID:28787456

Transport and storage of anthropogenic C across the Greenland-Portugal OVIDE section: Observations vs NEMO-PISCES

NASA Astrophysics Data System (ADS)

Gehlen, M.; Racapé, V.; Zunino, P.; Lherminier, P.; Bopp, L.; Mercier, H.

2016-02-01

Authors: Racapé V., Zunino P., Lherminier P., Bopp L., Mercier, H. and Gehlen M. At present, the ocean takes up approximately one-third of total anthropogenic carbon dioxide emissions. The North Atlantic Ocean is a major sink region for anthropogenic carbon (CANT) and a major contributor to its storage and transport. While evidence is growing that storage and transport are variable on interannual to decadal timescales, their evolution in recent decades and in the future remains uncertain. The variability is thought to be controlled in large part by the intensity of the meridional overturning circulation (MOC), which is suggested to slow down over the 21st century. This study aims to investigate the relationship between CANT transport across the Greenland-Portugal OVIDE section and Cant storage in the North Atlantic basin, as well as their combined evolution over the past 40 years. It relies on the combination of a pluriannual data set and output from the global biogeochemical ocean general circulation model NEMO/PISCES at 1/2° spatial resolution forced by the atmospheric reanalysis DFS4.2. Based on an observation-model comparison, the CANT advective transport is largely underestimated by the model (5 times) compared to the data-based estimate. However, the vertical gradient of CANT in the water column is well reproduced by NEMO/PISCES, supporting the use of a novel indicator computed by Zunino et al. (2014) to express the variability of CANT transport (T°CANT). Following the approach by Zunino et al. (2014), the estimator, T°CANT, was first derived in the model from MOCσ and DELTA-CANT (the vertical gradient of CANT between the upper and the lower branch of MOCσ) averaged over the month of June. Next, the representativity of T°CANT derived from a single sampling event per year was evaluated against estimates computed from annual mean values of MOCσ and DELTA-CANT. After evaluation of the model skill over the period covered by observations, the model is used

Essential fatty acids and their metabolites as modulators of stem cell biology with reference to inflammation, cancer, and metastasis.

PubMed

Das, Undurti N

2011-12-01

Stem cells are pluripotent and expected to be of benefit in the management of coronary heart disease, stroke, diabetes mellitus, cancer, and Alzheimer's disease in which pro-inflammatory cytokines are increased. Identifying endogenous bioactive molecules that have a regulatory role in stem cell survival, proliferation, and differentiation may aid in the use of stem cells in various diseases including cancer. Essential fatty acids form precursors to both pro- and anti-inflammatory molecules have been shown to regulate gene expression, enzyme activity, modulate inflammation and immune response, gluconeogenesis via direct and indirect pathways, function directly as agonists of a number of G protein-coupled receptors, activate phosphatidylinositol 3-kinase/Akt and p44/42 mitogen-activated protein kinases, and stimulate cell proliferation via Ca(2+), phospholipase C/protein kinase, events that are also necessary for stem cell survival, proliferation, and differentiation. Hence, it is likely that bioactive lipids play a significant role in various diseases by modulating the proliferation and differentiation of embryonic stem cells in addition to their capacity to suppress inflammation. Ephrin Bs and reelin, adhesion molecules, and microRNAs regulate neuronal migration and cancer cell metastasis. Polyunsaturated fatty acids and their products seem to modulate the expression of ephrin Bs and reelin and several adhesion molecules and microRNAs suggesting that bioactive lipids participate in neuronal regeneration and stem cell proliferation, migration, and cancer cell metastasis. Thus, there appears to be a close interaction among essential fatty acids, their bioactive products, and inflammation and cancer growth and its metastasis.

The PP4R1 sub-unit of protein phosphatase PP4 is essential for inhibition of NF-κB by merkel polyomavirus small tumour antigen.

PubMed

Abdul-Sada, Hussein; Müller, Marietta; Mehta, Rajni; Toth, Rachel; Arthur, J Simon C; Whitehouse, Adrian; Macdonald, Andrew

2017-04-11

Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with a high metastatic potential. The majority of MCC cases are caused by the Merkel cell polyomavirus (MCPyV), through expression of the virus-encoded tumour antigens. Whilst mechanisms attributing tumour antigen expression to transformation are being uncovered, little is known of the mechanisms by which MCPyV persists in the host. We previously identified the MCPyV small T antigen (tAg) as a novel inhibitor of nuclear factor kappa B (NF-kB) signalling and a modulator of the host anti-viral response. Here we demonstrate that regulation of NF-kB activation involves a previously undocumented interaction between tAg and regulatory sub-unit 1 of protein phosphatase 4 (PP4R1). Formation of a complex with PP4R1 and PP4c is required to bridge MCPyV tAg to the NEMO adaptor protein, allowing deactivation of the NF-kB pathway. Mutations in MCPyV tAg that fail to interact with components of this complex, or siRNA depletion of PP4R1, prevents tAg-mediated inhibition of NF-kB and pro-inflammatory cytokine production. Comparison of tAg binding partners from other human polyomavirus demonstrates that interactions with NEMO and PP4R1 are unique to MCPyV. Collectively, these data identify PP4R1 as a novel target for virus subversion of the host anti-viral response.

Implementation of the NEMO model for estimating the spread of leakage from chemical munitions in the Baltic Sea - the first approach

NASA Astrophysics Data System (ADS)

Andrzejewski, Jan

2017-04-01

After the Second World War, during the Potsdam Conference a decision about demilitarization of Germany was made, and as a consequence, ammunition including chemical warfare agents (CWA) was dumped into the basins of the Baltic Sea. This type of weapon was stored in metal barrels that were under strong influence of electrochemical oxidation, also known as corrosion. Several tens years later, scientists were wondering what consequences for marine ecosystem could a leakage from this weapon bring. Although over 70 years passed since the Second World War, the influence of potential leakage of the CWA has not been properly estimated. Thus, the main goal of this work is to estimate dangerous area caused by potential leakage using the NEMO (Nucleus for European Modelling of the Ocean) ocean model. The NEMO ocean model is developed by the European Consortium including research institutes from France, England and Italy. The first step of this work is to implement the model for the area of the Baltic Sea. It requires generation of horizontal and vertical grid, bathymetry, atmospheric forces and lateral boundary conditions. Implemented model will have to be checked - it means it will have to pass a validation process. The Baltic Sea is one of the best measured sea in the World - as a consequence a lot of data are freely available for researchers. After validation and tuning up the model, implementation of passive tracer is planned. Passive tracer is the prognostic variable that could represent concentration of potential leakage and does not have influence on the density of the model. Based on distribution of the passive tracer, dangerous areas in the locations of dumpsites will be assessed. The research work was funded by the European Union (European Regional Development Fund) under the Interreg Baltic Sea Region Programme 2014-2020, project #R013 DAIMON (Decision Aid for Marine Munitions).

Assessing activity of Hepatitis A virus 3C protease using a cyclized luciferase-based biosensor.

PubMed

Zhou, Junwei; Wang, Dang; Xi, Yongqiang; Zhu, Xinyu; Yang, Yuting; Lv, Mengting; Luo, Chuanzhen; Chen, Jiyao; Ye, Xu; Fang, Liurong; Xiao, Shaobo

2017-07-08

Hepatitis A is an acute infection caused by Hepatitis A virus (HAV), which is widely distributed throughout the world. The HAV 3C cysteine protease (3C pro ), an important nonstructural protein, is responsible for most cleavage within the viral polyprotein and is critical for the processes of viral replication. Our group has previously demonstrated that HAV 3C pro cleaves human NF-κB essential modulator (NEMO), a kinase required in interferon signaling. Based on this finding, we generated four luciferase-based biosensors containing the NEMO sequence (PVLKAQ↓ADIYKA) that is cleaved by HAV 3C pro and/or the Nostoc punctiforme DnaE intein, to monitor the activity of HAV 3C pro in human embryonic kidney cells (HEK-293T). Western blotting showed that HAV 3C pro recognized and cleaved the NEMO cleavage sequence incorporated in the four biosensors, whereas only one cyclized luciferase-based biosensor (233-DnaE-HAV, 233DH) showed a measurable and reliable increase in firefly luciferase activity, with very low background, in the presence of HAV 3C pro . With this biosensor (233DH), we monitored HAV 3C pro activity in HEK-293T cells, and tested it against a catalytically deficient mutant HAV 3C pro and other virus-encoded proteases. The results showed that the activity of this luciferase biosensor is specifically dependent on HAV 3C pro . Collectively, our data demonstrate that the luciferase biosensor developed here might provide a rapid, sensitive, and efficient evaluation of HAV 3C pro activity, and should extend our better understanding of the biological relevance of HAV 3C pro . Copyright © 2017 Elsevier Inc. All rights reserved.

Black pepper (Piper nigrum) essential oil demonstrates tissue remodeling and metabolism modulating potential in human cells.

PubMed

Han, Xuesheng; Beaumont, Cody; Rodriguez, Damian; Bahr, Tyler

2018-05-17

Very few studies have investigated the biological activities of black pepper essential oil (BPEO) in human cells. Therefore, in the current study, we examined the biological activities of BPEO in cytokine-stimulated human dermal fibroblasts by analyzing the levels of 17 important protein biomarkers pertinent to inflammation and tissue remodeling. BPEO exhibited significant antiproliferative activity in these skin cells and significantly inhibited the production of Collagen I, Collagen III, and plasminogen activator inhibitor 1. In addition, we studied the effect of BPEO on the regulation of genome-wide expression and found that BPEO diversely modulated global gene expression. Further analysis showed that BPEO affected many important genes and signaling pathways closely related to metabolism, inflammation, tissue remodeling, and cancer signaling. This study is the first to provide evidence of the biological activities of BPEO in human dermal fibroblasts. The data suggest that BPEO possesses promising potential to modulate the biological processes of tissue remodeling, wound healing, and metabolism. Although further research is required, BPEO appears to be a good therapeutic candidate for a variety of health conditions including wound care and metabolic diseases. Research into the biological and pharmacological mechanisms of action of BPEO and its major active constituents is recommended. Copyright © 2018 John Wiley & Sons, Ltd.

Thermodynamic and dynamic ice thickness contributions in the Canadian Arctic Archipelago in NEMO-LIM2 numerical simulations

NASA Astrophysics Data System (ADS)

Hu, Xianmin; Sun, Jingfan; Chan, Ting On; Myers, Paul G.

2018-04-01

Sea ice thickness evolution within the Canadian Arctic Archipelago (CAA) is of great interest to science, as well as local communities and their economy. In this study, based on the NEMO numerical framework including the LIM2 sea ice module, simulations at both 1/4 and 1/12° horizontal resolution were conducted from 2002 to 2016. The model captures well the general spatial distribution of ice thickness in the CAA region, with very thick sea ice (˜ 4 m and thicker) in the northern CAA, thick sea ice (2.5 to 3 m) in the west-central Parry Channel and M'Clintock Channel, and thin ( < 2 m) ice (in winter months) on the east side of CAA (e.g., eastern Parry Channel, Baffin Island coast) and in the channels in southern areas. Even though the configurations still have resolution limitations in resolving the exact observation sites, simulated ice thickness compares reasonably (seasonal cycle and amplitudes) with weekly Environment and Climate Change Canada (ECCC) New Ice Thickness Program data at first-year landfast ice sites except at the northern sites with high concentration of old ice. At 1/4 to 1/12° scale, model resolution does not play a significant role in the sea ice simulation except to improve local dynamics because of better coastline representation. Sea ice growth is decomposed into thermodynamic and dynamic (including all non-thermodynamic processes in the model) contributions to study the ice thickness evolution. Relatively smaller thermodynamic contribution to ice growth between December and the following April is found in the thick and very thick ice regions, with larger contributions in the thin ice-covered region. No significant trend in winter maximum ice volume is found in the northern CAA and Baffin Bay while a decline (r2 ≈ 0.6, p < 0.01) is simulated in Parry Channel region. The two main contributors (thermodynamic growth and lateral transport) have high interannual variabilities which largely balance each other, so that maximum ice volume can

Physical Education: Essential Issues

ERIC Educational Resources Information Center

Green, Ken, Ed.; Hardman, Ken, Ed.

2005-01-01

This book is aimed primarily at under and postgraduate students pursuing entire programmes or discrete courses and modules in the broad area of physical education and sport in schools. It consists of a collection of what is considered to be essential readings in the sense that they are contributions from eminent authors on a breadth of salient…

South Atlantic meridional transports from NEMO-based simulations and reanalyses

NASA Astrophysics Data System (ADS)

Mignac, Davi; Ferreira, David; Haines, Keith

2018-02-01

The meridional heat transport (MHT) of the South Atlantic plays a key role in the global heat budget: it is the only equatorward basin-scale ocean heat transport and it sets the northward direction of the global cross-equatorial transport. Its strength and variability, however, are not well known. The South Atlantic transports are evaluated for four state-of-the-art global ocean reanalyses (ORAs) and two free-running models (FRMs) in the period 1997-2010. All products employ the Nucleus for European Modelling of the Oceans (NEMO) model, and the ORAs share very similar configurations. Very few previous works have looked at ocean circulation patterns in reanalysis products, but here we show that the ORA basin interior transports are consistently improved by the assimilated in situ and satellite observations relative to the FRMs, especially in the Argo period. The ORAs also exhibit systematically higher meridional transports than the FRMs, which is in closer agreement with observational estimates at 35 and 11° S. However, the data assimilation impact on the meridional transports still greatly varies among the ORAs, leading to differences up to ˜ 8 Sv and 0.4 PW in the South Atlantic Meridional Overturning Circulation and the MHTs, respectively. We narrow this down to large inter-product discrepancies in the western boundary currents (WBCs) at both upper and deep levels explaining up to ˜ 85 % of the inter-product differences in MHT. We show that meridional velocity differences, rather than temperature differences, in the WBCs drive ˜ 83 % of this MHT spread. These findings show that the present ocean observation network and data assimilation schemes can be used to consistently constrain the South Atlantic interior circulation but not the overturning component, which is dominated by the narrow western boundary currents. This will likely limit the effectiveness of ORA products for climate or decadal prediction studies.

TAB2 Is Essential for Prevention of Apoptosis in Fetal Liver but Not for Interleukin-1 Signaling

PubMed Central

Sanjo, Hideki; Takeda, Kiyoshi; Tsujimura, Tohru; Ninomiya-Tsuji, Jun; Matsumoto, Kunihiro; Akira, Shizuo

2003-01-01

The proinflammatory cytokine interleukin-1 (IL-1) transmits a signal via several critical cytoplasmic proteins such as MyD88, IRAKs and TRAF6. Recently, serine/threonine kinase TAK1 and TAK1 binding protein 1 and 2 (TAB1/2) have been identified as molecules involved in IL-1-induced TRAF6-mediated activation of AP-1 and NF-κB via mitogen-activated protein (MAP) kinases and IκB kinases, respectively. However, their physiological functions remain to be clarified. To elucidate their roles in vivo, we generated TAB2-deficient mice. The TAB2 deficiency was embryonic lethal due to liver degeneration and apoptosis. This phenotype was similar to that of NF-κB p65-, IKKβ-, and NEMO/IKKγ-deficient mice. However, the IL-1-induced activation of NF-κB and MAP kinases was not impaired in TAB2-deficient embryonic fibroblasts. These findings demonstrate that TAB2 is essential for embryonic development through prevention of liver apoptosis but not for the IL-1 receptor-mediated signaling pathway. PMID:12556483

MAVS ubiquitination by the E3 ligase TRIM25 and degradation by the proteasome is involved in type I interferon production after activation of the antiviral RIG-I-like receptors

PubMed Central

2012-01-01

Background During a viral infection, the intracellular RIG-I-like receptors (RLRs) sense viral RNA and signal through the mitochondrial antiviral signaling adaptor MAVS (also known as IPS-1, Cardif and VISA) whose activation triggers a rapid production of type I interferons (IFN) and of pro-inflammatory cytokines through the transcription factors IRF3/IRF7 and NF-κB, respectively. While MAVS is essential for this signaling and known to operate through the scaffold protein NEMO and the protein kinase TBK1 that phosphorylates IRF3, its mechanism of action and regulation remain unclear. Results We report here that RLR activation triggers MAVS ubiquitination on lysine 7 and 10 by the E3 ubiquitin ligase TRIM25 and marks it for proteasomal degradation concomitantly with downstream signaling. Inhibition of this MAVS degradation with a proteasome inhibitor does not affect NF-κB signaling but it hampers IRF3 activation, and NEMO and TBK1, two essential mediators in type I IFN production, are retained at the mitochondria. Conclusions These results suggest that MAVS functions as a recruitment platform that assembles a signaling complex involving NEMO and TBK1, and that the proteasome-mediated MAVS degradation is required to release the signaling complex into the cytosol, allowing IRF3 phosphorylation by TBK1. PMID:22626058

MAVS ubiquitination by the E3 ligase TRIM25 and degradation by the proteasome is involved in type I interferon production after activation of the antiviral RIG-I-like receptors.

PubMed

Castanier, Céline; Zemirli, Naima; Portier, Alain; Garcin, Dominique; Bidère, Nicolas; Vazquez, Aimé; Arnoult, Damien

2012-05-24

During a viral infection, the intracellular RIG-I-like receptors (RLRs) sense viral RNA and signal through the mitochondrial antiviral signaling adaptor MAVS (also known as IPS-1, Cardif and VISA) whose activation triggers a rapid production of type I interferons (IFN) and of pro-inflammatory cytokines through the transcription factors IRF3/IRF7 and NF-κB, respectively. While MAVS is essential for this signaling and known to operate through the scaffold protein NEMO and the protein kinase TBK1 that phosphorylates IRF3, its mechanism of action and regulation remain unclear. We report here that RLR activation triggers MAVS ubiquitination on lysine 7 and 10 by the E3 ubiquitin ligase TRIM25 and marks it for proteasomal degradation concomitantly with downstream signaling. Inhibition of this MAVS degradation with a proteasome inhibitor does not affect NF-κB signaling but it hampers IRF3 activation, and NEMO and TBK1, two essential mediators in type I IFN production, are retained at the mitochondria. These results suggest that MAVS functions as a recruitment platform that assembles a signaling complex involving NEMO and TBK1, and that the proteasome-mediated MAVS degradation is required to release the signaling complex into the cytosol, allowing IRF3 phosphorylation by TBK1.

NEMO-Binding Domain Peptide Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting the NF-κB Signaling Pathway

PubMed Central

Huang, Jianhua; Li, Li; Yuan, Weifeng; Zheng, Linxin

2016-01-01

The aim of the present study is to investigate the protective effects and relevant mechanisms exerted by NEMO-binding domain peptide (NBD) against lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice. The ALI model was induced by intratracheally administered atomized LPS (5 mg/kg) to BABL/c mice. Half an hour before LPS administration, we treated the mice with increasing concentrations of intratracheally administered NBD or saline aerosol. Two hours after LPS administration, each group of mice was sacrificed. We observed that NBD pretreatment significantly attenuated LPS-induced lung histopathological injury in a dose-dependent manner. Western blotting established that NBD pretreatment obviously attenuated LPS-induced IκB-α and NF-κBp65 activation and NOX1, NOX2, and NOX4 overexpression. Furthermore, NBD pretreatment increased SOD and T-AOC activity and decreased MDA levels in lung tissue. In addition, NBD also inhibited TNF-α and IL-1β secretion in BALF after LPS challenge. In conclusion, NBD protects against LPS-induced ALI in mice. PMID:27956761

Intestinal exposure to PCB 153 induces inflammation via the ATM/NEMO pathway.

PubMed

Phillips, Matthew C; Dheer, Rishu; Santaolalla, Rebeca; Davies, Julie M; Burgueño, Juan; Lang, Jessica K; Toborek, Michal; Abreu, Maria T

2018-01-15

Polychlorinated biphenyls (PCBs) are persistent organic pollutants that adversely affect human health. PCBs bio-accumulate in organisms important for human consumption. PCBs accumulation in the body leads to activation of the transcription factor NF-κB, a major driver of inflammation. Despite dietary exposure being one of the main routes of exposure to PCBs, the gut has been widely ignored when studying the effects of PCBs. We investigated the effects of PCB 153 on the intestine and addressed whether PCB 153 affected intestinal permeability or inflammation and the mechanism by which this occurred. Mice were orally exposed to PCB 153 and gut permeability was assessed. Intestinal epithelial cells (IECs) were collected and evaluated for evidence of genotoxicity and inflammation. A human IEC line (SW480) was used to examine the direct effects of PCB 153 on epithelial function. NF-кB activation was measured using a reporter assay, DNA damage was assessed, and cytokine expression was ascertained with real-time PCR. Mice orally exposed to PCB 153 had an increase in intestinal permeability and inflammatory cytokine expression in their IECs; inhibition of NF-кB ameliorated both these effects. This inflammation was associated with genotoxic damage and NF-кB activation. Exposure of SW480 cells to PCB 153 led to similar effects as seen in vivo. We found that activation of the ATM/NEMO pathway by genotoxic stress was upstream of NF-kB activation. These results demonstrate that oral exposure to PCB 153 is genotoxic to IECs and induces downstream inflammation and barrier dysfunction in the intestinal epithelium. Copyright © 2017 Elsevier Inc. All rights reserved.

Emergence of the A20/ABIN-mediated inhibition of NF-κB signaling via modifying the ubiquitinated proteins in a basal chordate.

PubMed

Yuan, Shaochun; Dong, Xiangru; Tao, Xin; Xu, Liqun; Ruan, Jie; Peng, Jian; Xu, Anlong

2014-05-06

In the past decade, ubiquitination has been well documented to have multifaceted roles in regulating NF-κB activation in mammals. However, its function, especially how deubiquitinating enzymes balance the NF-κB activation, remains largely elusive in invertebrates. Investigating bbtA20 and its binding proteins, bbt A20-binding inhibitor of NF-κB (bbtABIN1) and bbtABIN2, in Chinese amphioxus Branchiostoma belcheri tsingtauense, we found that bbtABIN2 can colocalize and compete with bbt TNF receptor-associated factor 6 to connect the K63-linked polyubiquitin chains, whereas bbtABIN1 physically links bbtA20 to bbt NF-κB essential modulator (bbtNEMO) to facilitate the K48-linked ubiquitination of bbtNEMO. Similar to human A20, bbtA20 is a dual enzyme that removes the K63-linked polyubiquitin chains and builds the K48-linked polyubiquitin chains on bbt receptor-interacting serine/threonine protein kinase 1b, leading to the inhibition of NF-κB signaling. Our study not only suggests that ubiquitination is an ancient strategy in regulating NF-κB activation but also provides the first evidence, to our knowledge, for ABINs/A20-mediated inhibition of NF-κB via modifying the ubiquitinated proteins in a basal chordate, adding information on the stepwise development of vertebrate innate immune signaling.

Electro-optic modulator with ultra-low residual amplitude modulation for frequency modulation and laser stabilization.

PubMed

Tai, Zhaoyang; Yan, Lulu; Zhang, Yanyan; Zhang, Xiaofei; Guo, Wenge; Zhang, Shougang; Jiang, Haifeng

2016-12-01

The reduction of the residual amplitude modulation (RAM) induced by electro-optic modulation is essential for many applications of frequency modulation spectroscopy requiring a lower system noise floor. Here, we demonstrate a simple passive approach employing an electro-optic modulator (EOM) cut at Brewster's angle. The proposed EOM exhibits a RAM of a few parts per million, which is comparable with that achieved by a common EOM under critical active temperature and bias voltage controls. The frequency instability of a 10 cm cavity-stabilized laser induced by the RAM effect of the proposed EOM is below 3×10^-17 for integration times from 1 to 1000 s, and below 4×10^-16 for comprehensive noise contributions for integration times from 1 to 100 s.

Interactions between Arctic sea ice drift, concentration and thickness modeled by NEMO-LIM3 at different resolutions

NASA Astrophysics Data System (ADS)

Docquier, David; Massonnet, François; Raulier, Jonathan; Lecomte, Olivier; Fichefet, Thierry

2016-04-01

Sea ice concentration and thickness have substantially decreased in the Arctic since the beginning of the satellite era. As a result, mechanical strength has decreased allowing more fracturing and leading to increased sea ice drift. However, recent studies have highlighted that the interplay between sea ice thermodynamics and dynamics is poorly represented in contemporary global climate model (GCM) simulations. Thus, the considerable inter-model spread in terms of future sea ice extent projections could be reduced by better understanding the interactions between drift, concentration and thickness. This study focuses on the results coming from the global coupled ocean-sea ice model NEMO-LIM3 between 1979 and 2012. Three different simulations are forced by the Drakkar Forcing Set (DFS) 5.2 and run on the global tripolar ORCA grid at spatial resolutions of 0.25, 1° and 2°. The relation between modeled sea ice drift, concentration and thickness is further analyzed, compared to observations and discussed in the framework of the above-mentioned poor representation. It is proposed as a process-based metric for evaluating model performance. This study forms part of the EU Horizon 2020 PRIMAVERA project aiming at developing a new generation of advanced and well-evaluated high-resolution GCMs.

Electromechanical Componentry. High-Technology Training Module.

ERIC Educational Resources Information Center

Lindemann, Don

This training module on electromechanical components contains 10 units for a two-year vocational program packaging system equipment control course at Wisconsin Indianhead Technical College. This module describes the functions of electromechanical devices essential for understanding input/output devices for Programmable Logic Control (PLC)…

Nutrigenomics of essential oils and their potential domestic use for improving health.

PubMed

Cayuela Sánchez, José Antonio; Elamrani, Abdelaziz

2014-11-01

The use of essential oils as industrial food additives is notorious, like their medicinal properties. However, their use in household food spicing is for now limited. In this work, we have made a review to reveal the nutrigenomic actions exerted by their bioactive components, to promote awareness of their modulating gene expression ability and the potential that this implies. Also considered is how essential oils can be used as flavoring and seasoning after cooking and before consumption, such as diet components which can improve human health. Genetic mechanisms involved in the medicinal properties of essential oils for food use are identified from literature. These genetic mechanisms reveal nutrigenomic actions. Reviews on the medicinal properties of essential oils have been particularly considered. A wide diversity of nutrigenomic effects from essential oils useful potentially for food spicing is reviewed. General ideas are discussed about essential oils and their properties, such as anti-inflammatory, analgesic, immunomodulatory, anticancer, hepatoprotective, hypolipidemic, anti-diabetic, antioxidant, bone-reparation, anti-depressant and mitigatory for Alzheimer's disease. The essential oils for food use are potentially promoting health agents, and, therefore, worth using as flavoring and condiments. Becoming aware of the modulating gene expression actions from essential oils is important for understanding their potential for use in household dishes as spices to improve health.

V-band integrated quadriphase modulator

NASA Technical Reports Server (NTRS)

Grote, A.; Chang, K.

1983-01-01

A V-band integrated circuit quadriphase shift keyed modulator/exciter for space communications systems was developed. Intersatellite communications systems require direct modulation at 60 GHz to enhance signal processing capability. For most systems, particularly space applications, small and lightweight components are essential to alleviate severe system design constraints. Thus to achieve wideband, high data rate systems, direct modulation techniques at millimeter waves using solid state integrated circuit technology are an integral part of the overall technology developments.

Response of water temperature to surface wave effects in the Baltic Sea: simulations with the coupled NEMO-WAM model

NASA Astrophysics Data System (ADS)

Alari, Victor; Staneva, Joanna; Breivik, Øyvind; Bidlot, Jean-Raymond; Mogensen, Kristian; Janssen, Peter

2016-04-01

The effects of wind waves on the Baltic Sea water temperature has been studied by coupling the hydrodynamical model NEMO with the wave model WAM. The wave forcing terms that have been taken into consideration are: Stokes-Coriolis force, seastate dependent energy flux and sea-state dependent momentum flux. The combined role of these processes as well as their individual contributions on simulated temperature is analysed. The results indicate a pronounced effect of waves on surface temperature, on the distribution of vertical temperature and on upwellinǵs. In northern parts of the Baltic Sea a warming of the surface layer occurs in the wave included simulations. This in turn reduces the cold bias between simulated and measured data. The warming is primarily caused by sea-state dependent energy flux. Wave induced cooling is mostly observed in near coastal areas and is mainly due to Stokes-Coriolis forcing. The latter triggers effect of intensifying upwellings near the coasts, depending on the direction of the wind. The effect of sea-state dependent momentum flux is predominantly to warm the surface layer. During the summer the wave induced water temperature changes were up to 1 °C.

Measurement of the double-{beta} decay half-life of {sup 150}Nd and search for neutrinoless decay modes with the NEMO-3 detector

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

Argyriades, J.; Augier, C.; Bongrand, M.

2009-09-15

The half-life for double-{beta} decay of {sup 150}Nd has been measured by the NEMO-3 experiment at the Modane Underground Laboratory. Using 924.7 days of data recorded with 36.55 g of {sup 150}Nd, we measured the half-life for 2{nu}{beta}{beta} decay to be T{sub 1/2}{sup 2{nu}}=(9.11{sub -0.22}{sup +0.25}(stat.){+-}0.63(syst.))x10{sup 18} yr. The observed limit on the half-life for neutrinoless double-{beta} decay is found to be T{sub 1/2}{sup 0{nu}}>1.8x10{sup 22} yr at 90% confidence level. This translates into a limit on the effective Majorana neutrino mass of <4.0-6.3 eV if the nuclear deformation is taken into account. We also set limits on modelsmore » involving Majoron emission, right-handed currents, and transitions to excited states.« less

The nature of tremor circuits in parkinsonian and essential tremor

PubMed Central

Cagnan, Hayriye; Little, Simon; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Cheeran, Binith; Fitzgerald, James; Green, Alexander L.; Aziz, Tipu

2014-01-01

Tremor is a cardinal feature of Parkinson’s disease and essential tremor, the two most common movement disorders. Yet, the mechanisms underlying tremor generation remain largely unknown. We hypothesized that driving deep brain stimulation electrodes at a frequency closely matching the patient’s own tremor frequency should interact with neural activity responsible for tremor, and that the effect of stimulation on tremor should reveal the role of different deep brain stimulation targets in tremor generation. Moreover, tremor responses to stimulation might reveal pathophysiological differences between parkinsonian and essential tremor circuits. Accordingly, we stimulated 15 patients with Parkinson’s disease with either thalamic or subthalamic electrodes (13 male and two female patients, age: 50–77 years) and 10 patients with essential tremor with thalamic electrodes (nine male and one female patients, age: 34–74 years). Stimulation at near-to tremor frequency entrained tremor in all three patient groups (ventrolateral thalamic stimulation in Parkinson’s disease, P = 0.0078, subthalamic stimulation in Parkinson’s disease, P = 0.0312; ventrolateral thalamic stimulation in essential tremor, P = 0.0137; two-tailed paired Wilcoxon signed-rank tests). However, only ventrolateral thalamic stimulation in essential tremor modulated postural tremor amplitude according to the timing of stimulation pulses with respect to the tremor cycle (e.g. P = 0.0002 for tremor amplification, two-tailed Wilcoxon rank sum test). Parkinsonian rest and essential postural tremor severity (i.e. tremor amplitude) differed in their relative tolerance to spontaneous changes in tremor frequency when stimulation was not applied. Specifically, the amplitude of parkinsonian rest tremor remained unchanged despite spontaneous changes in tremor frequency, whereas that of essential postural tremor reduced when tremor frequency departed from median values. Based on these results we conclude that

N-terminus of Cardiac Myosin Essential Light Chain Modulates Myosin Step-Size

PubMed Central

Wang, Yihua; Ajtai, Katalin; Kazmierczak, Katarzyna; Szczesna-Cordary, Danuta; Burghardt, Thomas P.

2016-01-01

Muscle myosin cyclically hydrolyzes ATP to translate actin. Ventricular cardiac myosin (βmys) moves actin with three distinct unitary step-sizes resulting from its lever-arm rotation and with step-frequencies that are modulated in a myosin regulation mechanism. The lever-arm associated essential light chain (vELC) binds actin by its 43 residue N-terminal extension. Unitary steps were proposed to involve the vELC N-terminal extension with the 8 nm step engaging the vELC/actin bond facilitating an extra ~19 degrees of lever-arm rotation while the predominant 5 nm step forgoes vELC/actin binding. A minor 3 nm step is the unlikely conversion of the completed 5 to the 8 nm step. This hypothesis was tested using a 17 residue N-terminal truncated vELC in porcine βmys (Δ17βmys) and a 43 residue N-terminal truncated human vELC expressed in transgenic mouse heart (Δ43αmys). Step-size and step-frequency were measured using the Qdot motility assay. Both Δ17βmys and Δ43αmys had significantly increased 5 nm step-frequency and coincident loss in the 8 nm step-frequency compared to native proteins suggesting the vELC/actin interaction drives step-size preference. Step-size and step-frequency probability densities depend on the relative fraction of truncated vELC and relate linearly to pure myosin species concentrations in a mixture containing native vELC homodimer, two truncated vELCs in the modified homodimer, and one native and one truncated vELC in the heterodimer. Step-size and step-frequency, measured for native homodimer and at two or more known relative fractions of truncated vELC, are surmised for each pure species by using a new analytical method. PMID:26671638

User handbook for block IV silicon solar cell modules

NASA Technical Reports Server (NTRS)

Smokler, M. I.

1982-01-01

The essential electrical and mechanical characteristics of block 4 photovoltaic solar cell modules are described. Such module characteristics as power output, nominal operating voltage, current-voltage characteristics, nominal operating cell temperature, and dimensions are tabulated. The limits of the environmental and other stress tests to which the modules are subjected are briefly described.

AMM15: a new high-resolution NEMO configuration for operational simulation of the European north-west shelf

NASA Astrophysics Data System (ADS)

Graham, Jennifer A.; O'Dea, Enda; Holt, Jason; Polton, Jeff; Hewitt, Helene T.; Furner, Rachel; Guihou, Karen; Brereton, Ashley; Arnold, Alex; Wakelin, Sarah; Castillo Sanchez, Juan Manuel; Mayorga Adame, C. Gabriela

2018-02-01

This paper describes the next-generation ocean forecast model for the European north-west shelf, which will become the basis of operational forecasts in 2018. This new system will provide a step change in resolution and therefore our ability to represent small-scale processes. The new model has a resolution of 1.5 km compared with a grid spacing of 7 km in the current operational system. AMM15 (Atlantic Margin Model, 1.5 km) is introduced as a new regional configuration of NEMO v3.6. Here we describe the technical details behind this configuration, with modifications appropriate for the new high-resolution domain. Results from a 30-year non-assimilative run using the AMM15 domain demonstrate the ability of this model to represent the mean state and variability of the region.

Overall, there is an improvement in the representation of the mean state across the region, suggesting similar improvements may be seen in the future operational system. However, the reduction in seasonal bias is greater off-shelf than on-shelf. In the North Sea, biases are largely unchanged. Since there has been no change to the vertical resolution or parameterization schemes, performance improvements are not expected in regions where stratification is dominated by vertical processes rather than advection. This highlights the fact that increased horizontal resolution will not lead to domain-wide improvements. Further work is needed to target bias reduction across the north-west shelf region.

Antigiardial activity of Ocimum basilicum essential oil.

PubMed

de Almeida, Igor; Alviano, Daniela Sales; Vieira, Danielle Pereira; Alves, Péricles Barreto; Blank, Arie Fitzgerald; Lopes, Angela Hampshire C S; Alviano, Celuta Sales; Rosa, Maria do Socorro S

2007-07-01

In this study, we investigated the effects of Ocimum basilicum essential oil on Giardia lamblia and on the modulation of the interaction of these parasites by peritoneal mouse macrophage. The essential oil (2 mg/ml) and its purified substances demonstrated antigiardial activity. Linalool (300 microg/ml), however, was able to kill 100% parasites after 1 h of incubation, which demonstrates its high antigiardial potential. Pretreatment of peritoneal mouse macrophages with 2 mg/ml essential oil dilution reduced in 79% the association index between these macrophages and G. lamblia, with a concomitant increase by 153% on nitric oxide production by the G. lamblia-ingested macrophages. The protein profiles and proteolitic activity of these parasite trophozoites, previously treated or not with 2 mg/ml essential oil or with the purified fractions, were also determined. After 1 and 2 h of incubation, proteins of lysates and culture supernatants revealed significant differences in bands patterns when compared to controls. Besides, the proteolitic activity, mainly of cysteine proteases, was clearly inhibited by the essential oil (2 mg/ml) and the purified linalool (300 microg/ml). These results suggest that, with G. lamblia, the essential oil from O. basilicum and its purified compounds, specially linalool, have a potent antimicrobial activity.

Mechanism Underlying IκB Kinase Activation Mediated by the Linear Ubiquitin Chain Assembly Complex

PubMed Central

Fujita, Hiroaki; Akita, Mariko; Kato, Ryuichi; Sasaki, Yoshiteru; Wakatsuki, Soichi

2014-01-01

The linear ubiquitin chain assembly complex (LUBAC) ligase, consisting of HOIL-1L, HOIP, and SHARPIN, specifically generates linear polyubiquitin chains. LUBAC-mediated linear polyubiquitination has been implicated in NF-κB activation. NEMO, a component of the IκB kinase (IKK) complex, is a substrate of LUBAC, but the precise molecular mechanism underlying linear chain-mediated NF-κB activation has not been fully elucidated. Here, we demonstrate that linearly polyubiquitinated NEMO activates IKK more potently than unanchored linear chains. In mutational analyses based on the crystal structure of the complex between the HOIP NZF1 and NEMO CC2-LZ domains, which are involved in the HOIP-NEMO interaction, NEMO mutations that impaired linear ubiquitin recognition activity and prevented recognition by LUBAC synergistically suppressed signal-induced NF-κB activation. HOIP NZF1 bound to NEMO and ubiquitin simultaneously, and HOIP NZF1 mutants defective in interaction with either NEMO or ubiquitin could not restore signal-induced NF-κB activation. Furthermore, linear chain-mediated activation of IKK2 involved homotypic interaction of the IKK2 kinase domain. Collectively, these results demonstrate that linear polyubiquitination of NEMO plays crucial roles in IKK activation and that this modification involves the HOIP NZF1 domain and recognition of NEMO-conjugated linear ubiquitin chains by NEMO on another IKK complex. PMID:24469399

Technology for the Organic Chemist: Three Exploratory Modules

ERIC Educational Resources Information Center

Esteb, John J.; McNulty, LuAnne M.; Magers, John; Morgan, Paul; Wilson, Anne M.

2010-01-01

The ability to use computer-based technology is an essential skill set for students majoring in chemistry. This exercise details the introduction of appropriate uses for this technology in the organic chemistry series. The incorporation of chemically appropriate online resources (module 1), scientific databases (module 2), and the use of a…

Bergamot essential oil differentially modulates intracellular Ca2+ levels in vascular endothelial and smooth muscle cells: a new finding seen with fura-2.

PubMed

You, Ji H; Kang, Purum; Min, Sun Seek; Seol, Geun Hee

2013-04-01

In this study, we compared the effect of the essential oil of Citrus bergamia Risso [bergamot, bergamot essential oil (BEO)] on the intracellular Ca levels in vascular endothelial (EA) and mouse vascular smooth muscle (MOVAS) cells, using the fura-2 fluorescence technique. BEO caused an initial transient increase in intracellular Ca concentration ([Ca]i) in EA cells, followed by a decrease, whereas it induced a sustained increase in [Ca]i in MOVAS cells. Linalyl acetate (LA) as a major component of BEO-induced [Ca]i mobilization was similar to BEO in EA cells. The increase of [Ca]i by LA was higher in EA cells than in MOVAS cells. [Ca]i rise induced by extracellular Ca application was significantly blocked by BEO or LA in EA cells but not in MOVAS cells, suggesting that BEO and LA block Ca influx in EA cells. The present results suggest that BEO and LA differentially modulate intracellular Ca levels in vascular endothelial and smooth muscle cells. In addition, blockade of Ca influx by BEO and LA in EA cells may explain the protective effects of BEO on endothelial dysfunction associated with cardiovascular disease.

Simulation of double beta decay in the ''SeXe'' TPC

NASA Astrophysics Data System (ADS)

Mauger, F.

2007-04-01

In 2004, the NEMO collaboration has started some preliminary studies for a next-generation double beta decay experiment: SuperNEMO. The possibility to use a large gaseous TPC has been investigated using simulation and extrapolation of former experiments. In this talk, I report on the reasons why such techniques have not been selected in 2004 and led the NEMO collaboration to reuse the techniques implemented within the NEMO3 detector.

Aerosol Monitoring Mission using an Advanced Nanosatellite

NASA Astrophysics Data System (ADS)

Pranajaya, Freddy; Zee, Robert E.

The Space Flight Laboratory (SFL) at the University of Toronto Institute for Aerospace Studies (UTIAS) is currently developing a nanosatellite for the purpose of monitoring aerosol content in the atmosphere. The NEMO-AM (Nanosatellite for Earth Monitoring and Observation -Aerosol Monitoring) spacecraft is designed to perform multi-angle, dual-polarization observa-tions in three visible bands. The satellite is designed to detect aerosol content in the atmosphere over a specific region with a nominal ground resolution of up to 200 m and a minimum swath of 120 km. NEMO-AM is being built under a collaborative agreement between SFL and the Indian Space Research Organization (ISRO). SFL is responsible for the design, manufacturing and qualification of the spacecraft and the optical instrument. The NEMO-AM is based on the NEMO bus, which is the next evolution to the SFL Generic Nanosatellite Bus (GNB) technology. The NEMO bus has a primary structure measuring 20 cm by 20 cm by 40 cm and is capable of peak power generation up to 80W. A minimum of 30W is available to the payload. The high peak power generation enables the NEMO bus to support a dedicated state-of-the-art high speed transmitter. The NEMO bus is designed with a total mass of 15 kg, 9 kg of which is dedicated to the payload. It can be configured for full three-axis control with up to 1 arcmin pointing stability. NEMO spacecraft will be secured to launch vehicles using the XPOD Duo separation system. This paper will summarize the NEMO-AM mission and the innovative aspects of the NEMO bus.

Nuclear Technology. Course 28: Welding Inspection. Module 28-9, Weld Repair Control.

ERIC Educational Resources Information Center

Espy, John

This ninth in a series of ten modules for a course titled Welding Inspection describes the purposes, essential elements, and application of a weld control program. The module follows a typical format that includes the following sections: (1) introduction, (2) module prerequisites, (3) objectives, (4) notes to instructor/student, (5) subject…

Nuclear Technology. Course 31: Quality Assurance Practices. Module 31-5, Nonconforming Materials.

ERIC Educational Resources Information Center

Pritchard, Jim; Espy, John

This fifth in a series of eight modules for a course titled Quality Assurance Practices describes the essential elements of a nonconforming material control system, including purpose and application. The module follows a typical format that includes the following sections: (1) introduction, (2) module prerequisites, (3) objectives, (4) notes to…

Development and validation of a yoga module for Parkinson disease.

PubMed

Kakde, Noopur; Metri, Kashinath G; Varambally, Shivarama; Nagaratna, Raghuram; Nagendra, H R

2017-03-25

Background Parkinson's disease (PD), a progressive neurodegenerative disease, affects motor and nonmotor functions, leading to severe debility and poor quality of life. Studies have reported the beneficial role of yoga in alleviating the symptoms of PD; however, a validated yoga module for PD is unavailable. This study developed and validated an integrated yoga module(IYM) for PD. Methods The IYM was prepared after a thorough review of classical yoga texts and previous findings. Twenty experienced yoga experts, who fulfilled the inclusion criteria, were selected validating the content of the IYM. A total of 28 practices were included in the IYM, and each practice was discussed and rated as (i) not essential, (ii) useful but not essential, and (iii) essential; the content validity ratio (CVR) was calculated using Lawshe's formula. Results Data analysis revealed that of the 28 IYM practices, 21 exhibited significant content validity (cut-off value: 0.42, as calculated by applying Lawshe's formula for the CVR). Conclusions The IYM is valid for PD, with good content validity. However, future studies must determine the feasibility and efficacy of the developed module.

Essential protein discovery based on a combination of modularity and conservatism.

PubMed

Zhao, Bihai; Wang, Jianxin; Li, Xueyong; Wu, Fang-Xiang

2016-11-01

Essential proteins are indispensable for the survival of a living organism and play important roles in the emerging field of synthetic biology. Many computational methods have been proposed to identify essential proteins by using the topological features of interactome networks. However, most of these methods ignored intrinsic biological meaning of proteins. Researches show that essentiality is tied not only to the protein or gene itself, but also to the molecular modules to which that protein belongs. The results of this study reveal the modularity of essential proteins. On the other hand, essential proteins are more evolutionarily conserved than nonessential proteins and frequently bind each other. That is to say, conservatism is another important feature of essential proteins. Multiple networks are constructed by integrating protein-protein interaction (PPI) networks, time course gene expression data and protein domain information. Based on these networks, a new essential protein identification method is proposed based on a combination of modularity and conservatism of proteins. Experimental results show that the proposed method outperforms other essential protein identification methods in terms of a number essential protein out of top ranked candidates. Copyright © 2016. Published by Elsevier Inc.

Compact Multimedia Systems in Multi-chip Module Technology

NASA Technical Reports Server (NTRS)

Fang, Wai-Chi; Alkalaj, Leon

1995-01-01

This tutorial paper shows advanced multimedia system designs based on multi-chip module (MCM) technologies that provide essential computing, compression, communication, and storage capabilities for various large scale information highway applications.!.

SRC-2 is an essential coactivator for orchastrating metabolism and circadian rhythm

USDA-ARS?s Scientific Manuscript database

Synchrony of the mammalian circadian clock is achieved by complex transcriptional and translational feedback loops centered on the BMAL1:CLOCK heterodimer. Modulation of circadian feedback loops is essential for maintaining rhythmicity, yet the role of transcriptional coactivators in driving BMAL1:C...

Development of Prototype Outcomes-Based Training Modules for Aesthetic Dentistry

ERIC Educational Resources Information Center

Andres, Maricar Joy T.; Borabo, Milagros L.

2015-01-01

The objective of the study is to know the essential components of Aesthetic Dentistry that will be a basis for prototype Outcomes-based training modules. Using a 5-point Likert scale, the researcher-made questionnaire assessed the different elements of Aesthetic Dentistry which are needed in the designing of the training module, the manner of…

A system view and analysis of essential hypertension.

PubMed

Botzer, Alon; Grossman, Ehud; Moult, John; Unger, Ron

2018-05-01

The goal of this study was to investigate genes associated with essential hypertension from a system perspective, making use of bioinformatic tools to gain insights that are not evident when focusing at a detail-based resolution. Using various databases (pathways, Genome Wide Association Studies, knockouts etc.), we compiled a set of about 200 genes that play a major role in hypertension and identified the interactions between them. This enabled us to create a protein-protein interaction network graph, from which we identified key elements, based on graph centrality analysis. Enriched gene regulatory elements (transcription factors and microRNAs) were extracted by motif finding techniques and knowledge-based tools. We found that the network is composed of modules associated with functions such as water retention, endothelial vasoconstriction, sympathetic activity and others. We identified the transcription factor SP1 and the two microRNAs miR27 (a and b) and miR548c-3p that seem to play a major role in regulating the network as they exert their control over several modules and are not restricted to specific functions. We also noticed that genes involved in metabolic diseases (e.g. insulin) are central to the network. We view the blood-pressure regulation mechanism as a system-of-systems, composed of several contributing subsystems and pathways rather than a single module. The system is regulated by distributed elements. Understanding this mode of action can lead to a more precise treatment and drug target discovery. Our analysis suggests that insulin plays a primary role in hypertension, highlighting the tight link between essential hypertension and diseases associated with the metabolic syndrome.

The Hedgehog Signal Induced Modulation of Bone Morphogenetic Protein Signaling: An Essential Signaling Relay for Urinary Tract Morphogenesis

PubMed Central

Nakagata, Naomi; Miyagawa, Shinichi; Suzuki, Kentaro; Kitazawa, Sohei; Yamada, Gen

2012-01-01

Background Congenital diseases of the urinary tract are frequently observed in infants. Such diseases present a number of developmental anomalies such as hydroureter and hydronephrosis. Although some genetically-modified mouse models of growth factor signaling genes reproduce urinary phenotypes, the pathogenic mechanisms remain obscure. Previous studies suggest that a portion of the cells in the external genitalia and bladder are derived from peri-cloacal mesenchymal cells that receive Hedgehog (Hh) signaling in the early developmental stages. We hypothesized that defects in such progenitor cells, which give rise to urinary tract tissues, may be a cause of such diseases. Methodology/Principal Findings To elucidate the pathogenic mechanisms of upper urinary tract malformations, we analyzed a series of Sonic hedgehog (Shh) deficient mice. Shh−/− displayed hydroureter and hydronephrosis phenotypes and reduced expression of several developmental markers. In addition, we suggested that Shh modulation at an early embryonic stage is responsible for such phenotypes by analyzing the Shh conditional mutants. Tissue contribution assays of Hh-responsive cells revealed that peri-cloacal mesenchymal cells, which received Hh signal secreted from cloacal epithelium, could contribute to the ureteral mesenchyme. Gain- and loss-of-functional mutants for Hh signaling revealed a correlation between Hh signaling and Bone morphogenetic protein (Bmp) signaling. Finally, a conditional ablation of Bmp receptor type IA (BmprIA) gene was examined in Hh-responsive cell lineages. This system thus made it possible to analyze the primary functions of the growth factor signaling relay. The defective Hh-to-Bmp signaling relay resulted in severe urinary tract phenotypes with a decrease in the number of Hh-responsive cells. Conclusions/Significance This study identified the essential embryonic stages for the pathogenesis of urinary tract phenotypes. These results suggested that Hh

Nemo regulates cell dynamics and represses the expression of miple, a midkine/pleiotrophin cytokine, during ommatidial rotation

PubMed Central

Muñoz-Soriano, Verónica; Ruiz, Carlos; Pérez-Alonso, Manuel; Mlodzik, Marek; Paricio, Nuria

2013-01-01

Ommatidial rotation is one of the most important events for correct patterning of the Drosophila eye. Although several signaling pathways are involved in this process, few genes have been shown to specifically affect it. One of them is nemo (nmo), which encodes a MAP-like protein kinase that regulates the rate of rotation throughout the entire process, and serves as a link between core planar cell polarity (PCP) factors and the E-cadherin–β-catenin complex. To determine more precisely the role of nmo in ommatidial rotation, live-imaging analyses in nmo mutant and wild-type early pupal eye discs were performed. We demonstrate that ommatidial rotation is not a continuous process, and that rotating and non-rotating interommatidial cells are very dynamic. Our in vivo analyses also show that nmo regulates the speed of rotation and is required in cone cells for correct ommatidial rotation, and that these cells as well as interommatidial cells are less dynamic in nmo mutants. Furthermore, microarray analyses of nmo and wild-type larval eye discs led us to identify new genes and signaling pathways related to nmo function during this process. One of them, miple, encodes the Drosophila ortholog of the midkine/pleiotrophin secreted cytokines that are involved in cell migration processes. miple is highly up-regulated in nmo mutant discs. Indeed, phenotypic analyses reveal that miple overexpression leads to ommatidial rotation defects. Genetic interaction assays suggest that miple is signaling through Ptp99A, the Drosophila ortholog of the vertebrate midkine/pleiotrophin PTPζ receptor. Accordingly, we propose that one of the roles of Nmo during ommatial rotation is to repress miple expression, which may in turn affect the dynamics in E-cadherin–β-catenin complexes. PMID:23428616

Surface wave effects on water temperature in the Baltic Sea: simulations with the coupled NEMO-WAM model

NASA Astrophysics Data System (ADS)

Alari, Victor; Staneva, Joanna; Breivik, Øyvind; Bidlot, Jean-Raymond; Mogensen, Kristian; Janssen, Peter

2016-08-01

Coupled circulation (NEMO) and wave model (WAM) system was used to study the effects of surface ocean waves on water temperature distribution and heat exchange at regional scale (the Baltic Sea). Four scenarios—including Stokes-Coriolis force, sea-state dependent energy flux (additional turbulent kinetic energy due to breaking waves), sea-state dependent momentum flux and the combination these forcings—were simulated to test the impact of different terms on simulated temperature distribution. The scenario simulations were compared to a control simulation, which included a constant wave-breaking coefficient, but otherwise was without any wave effects. The results indicate a pronounced effect of waves on surface temperature, on the distribution of vertical temperature and on upwelling's. Overall, when all three wave effects were accounted for, did the estimates of temperature improve compared to control simulation. During the summer, the wave-induced water temperature changes were up to 1 °C. In northern parts of the Baltic Sea, a warming of the surface layer occurs in the wave included simulations in summer months. This in turn reduces the cold bias between simulated and measured data, e.g. the control simulation was too cold compared to measurements. The warming is related to sea-state dependent energy flux. This implies that a spatio-temporally varying wave-breaking coefficient is necessary, because it depends on actual sea state. Wave-induced cooling is mostly observed in near-coastal areas and is the result of intensified upwelling in the scenario, when Stokes-Coriolis forcing is accounted for. Accounting for sea-state dependent momentum flux results in modified heat exchange at the water-air boundary which consequently leads to warming of surface water compared to control simulation.

Design and development of nEMoS, an all-in-one, low-cost, web-connected and 3D-printed device for environmental analysis.

PubMed

Salamone, Francesco; Belussi, Lorenzo; Danza, Ludovico; Ghellere, Matteo; Meroni, Italo

2015-06-04

The Indoor Environmental Quality (IEQ) refers to the quality of the environment in relation to the health and well-being of the occupants. It is a holistic concept, which considers several categories, each related to a specific environmental parameter. This article describes a low-cost and open-source hardware architecture able to detect the indoor variables necessary for the IEQ calculation as an alternative to the traditional hardware used for this purpose. The system consists of some sensors and an Arduino board. One of the key strengths of Arduino is the possibility it affords of loading the script into the board's memory and letting it run without interfacing with computers, thus granting complete independence, portability and accuracy. Recent works have demonstrated that the cost of scientific equipment can be reduced by applying open-source principles to their design using a combination of the Arduino platform and a 3D printer. The evolution of the 3D printer has provided a new means of open design capable of accelerating self-directed development. The proposed nano Environmental Monitoring System (nEMoS) instrument is shown to have good reliability and it provides the foundation for a more critical approach to the use of professional sensors as well as for conceiving new scenarios and potential applications.

Does antioxidant properties of the main component of essential oil reflect its antioxidant properties? The comparison of antioxidant properties of essential oils and their main components.

PubMed

Dawidowicz, Andrzej L; Olszowy, Małgorzata

2014-01-01

This study discusses the similarities and differences between the antioxidant activities of some essential oils: thyme (Thymus vulgaris), basil (Ocimum basilicum), peppermint (Mentha piperita), clove (Caryophyllus aromaticus), summer savory (Satureja hortensis), sage (Salvia hispanica) and lemon (Citrus limon (L.) Burm.) and of their main components (thymol or estragole or menthol or eugenol or carvacrol or camphor or limonene) estimated by using 2,2'-Diphenyl-1-picrylhydrazyl, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt and β-carotene bleaching assays. The obtained data show that the antioxidant properties of essential oil do not always depend on the antioxidant activity of its main component, and that they can be modulated by their other components. The conclusions concerning the interaction of essential oil components depend on the type of method applied for assessing the antioxidant activity. When comparing the antioxidant properties of essential oils and their main components, the concepts of synergism, antagonism and additivity are very relevant.

Electric-optic resonant phase modulator

NASA Technical Reports Server (NTRS)

Chen, Chien-Chung (Inventor); Robinson, Deborah L. (Inventor); Hemmati, Hamid (Inventor)

1994-01-01

An electro-optic resonant cavity is used to achieve phase modulation with lower driving voltages. Laser damage thresholds are inherently higher than with previously used integrated optics due to the utilization of bulk optics. Phase modulation is achieved at higher speeds with lower driving voltages than previously obtained with non-resonant electro-optic phase modulators. The instant scheme uses a data locking dither approach as opposed to the conventional sinusoidal locking schemes. In accordance with a disclosed embodiment, a resonant cavity modulator has been designed to operate at a data rate in excess of 100 Mbps. By carefully choosing the cavity finesse and its dimension, it is possible to control the pulse switching time to within 4 ns and to limit the required switching voltage to within 10 V. Experimentally, the resonant cavity can be maintained on resonance with respect to the input laser signal by monitoring the fluctuation of output intensity as the cavity is switched. This cavity locking scheme can be applied by using only the random data sequence, and without the need of additional dithering of the cavity. Compared to waveguide modulators, the resonant cavity has a comparable modulating voltage requirement. Because of its bulk geometry, resonant cavity modulator has the potential of accommodating higher throughput power. Furthermore, mode matching into a bulk device is easier and typically can be achieved with higher efficiency. On the other hand, unlike waveguide modulators which are essentially traveling wave devices, the resonant cavity modulator requires that the cavity be maintained in resonance with respect to the incoming laser signal. An additional control loop is incorporated into the modulator to maintain the cavity on resonance.

Anti-quorum sensing activity of essential oils from Colombian plants.

PubMed

Jaramillo-Colorado, Beatriz; Olivero-Verbel, Jesus; Stashenko, Elena E; Wagner-Döbler, Irene; Kunze, Brigitte

2012-01-01

Essential oils from Colombian plants were characterised by GC-MS, and assayed for anti-quorum sensing activity in bacteria sensor strains. Two major chemotypes were found for Lippia alba, the limonene-carvone and the citral (geranial-neral). For other species, the main components included α-pinene (Ocotea sp.), β-pinene (Swinglea glutinosa), cineol (Elettaria cardamomun), α-zingiberene (Zingiber officinale) and pulegone (Minthostachys mollis). Several essential oils presented promising inhibitory properties for the short chain AHL quorum sensing (QS) system, in Escherichia coli containing the biosensor plasmid pJBA132, in particular Lippia alba. Moderate activity as anti-QS using the same plasmid, were also found for selected constituents of essential oils studied here, such as citral, carvone and α-pinene, although solely at the highest tested concentration (250 µg mL(-1)). Only citral presented some activity for the long chain AHL QS system, in Pseudomonas putida containing the plasmid pRK-C12. In short, essential oils from Colombian flora have promising properties as QS modulators.

Wireless tracking of cotton modules Part II: automatic machine identification and system testing

USDA-ARS?s Scientific Manuscript database

Mapping the harvest location of cotton modules is essential to practical understanding and utilization of spatial-variability information in fiber quality. A wireless module-tracking system was recently developed, but automation of the system is required before it will find practical use on the far...

Carboxysomes: metabolic modules for CO 2 fixation

DOE PAGES

Turmo, Aiko; Gonzalez-Esquer, Cesar Raul; Kerfeld, Cheryl A.

2017-08-14

The carboxysome is a bacterial microcompartment encapsulating the enzymes carbonic anhydrase and ribulose-1,5-bisphosphate carboxylase/oxygenase. As the site of CO 2 fixation, it serves an essential role in the carbon dioxide concentrating mechanism of many chemoautotrophs and all cyanobacteria. Carboxysomes and other bacterial microcompartments self-assemble through specific protein–protein interactions that are typically mediated by conserved protein domains. In this review, we frame our current understanding of carboxysomes in the context of their component protein domains with their inherent function as the ‘building blocks’ of carboxysomes. These building blocks are organized in genetic modules (conserved chromosomal loci) that encode for carboxysomes andmore » ancillary proteins essential for the integration of the organelle with the rest of cellular metabolism. This conceptual framework provides the foundation for ‘plug-and-play’ engineering of carboxysomes as CO 2 fixation modules in a variety of biotechnological applications.« less

Growth regulating properties of isoprene and isoprenoid-based essential oils.

PubMed

Jones, Andrew Maxwell P; Shukla, Mukund R; Sherif, Sherif M; Brown, Paula B; Saxena, Praveen K

2016-01-01

Essential oils have growth regulating properties comparable to the well-documented methyl jasmonate and may be involved in localized and/or airborne plant communication. Aromatic plants employ large amounts of resources to produce essential oils. Some essential oils are known to contain compounds with plant growth regulating activities. However, the potential capacity of essential oils as airborne molecules able to modulate plant growth/development has remained uninvestigated. Here, we demonstrate that essential oils from eight taxonomically diverse plants applied in their airborne state inhibited auxin-induced elongation of Pisum sativum hypocotyls and Avena sativa coleoptiles. This response was also observed using five monoterpenes commonly found in essential oils as well as isoprene, the basic building block of terpenes. Upon transfer to ambient conditions, A. sativa coleoptiles resumed elongation, demonstrating an antagonistic relationship rather than toxicity. Inclusion of essential oils, monoterpenes, or isoprene into the headspace of culture vessels induced abnormal cellular growth along hypocotyls of Arabidopsis thaliana. These responses were also elicited by methyl jasmonate (MeJA); however, where methyl jasmonate inhibited root growth essential oils did not. Gene expression studies in A. thaliana also demonstrated differences between the MeJA and isoprenoid responses. This series of experiments clearly demonstrate that essential oils and their isoprenoid components interact with endogenous plant growth regulators when applied directly or as volatile components in the headspace. The similarities between isoprenoid and MeJA responses suggest that they may act in plant defence signalling. While further studies are needed to determine the ecological and evolutionary significance, the results of this study and the specialized anatomy associated with aromatic plants suggest that essential oils may act as airborne signalling molecules.

The Essential Oil from Origanum vulgare L. and Its Individual Constituents Carvacrol and Thymol Enhance the Effect of Tetracycline against Staphylococcus aureus.

PubMed

Cirino, Isis Caroline S; Menezes-Silva, Suellen Maria P; Silva, Helena Tainá D; de Souza, Evandro Leite; Siqueira-Júnior, José P

2014-01-01

In an ongoing project to evaluate essential oils as modulators of antibiotic resistance, the essential oil from Origanum vulgare L. (OVEO), as well as its individual constituents carvacrol (CAR) and thymol (THY), were investigated using Staphylococcus aureus strains possessing efflux mechanisms of resistance to norfloxacin, erythromycin and tetracycline. The minimum inhibitory concentration (MIC) values of the antibiotics were determined by agar dilution method, in the absence and in the presence of subinhibitory concentrations of OVEO, CAR or THY. Along with relevant antistaphylococcal activity, OVEO, CAR and THY modulated the activity of tetracycline, i.e. in combination with antibiotics a reduction in the MIC was observed (up to fourfold). The results presented here represent, as far as we know, the first report of OVEO, CAR and THY as putative efflux pump inhibitors. Broadly, these findings indicate that essential oils could serve as potential sources of compounds capable of modulating drug resistance. © 2015 S. Karger AG, Basel.

Design and Development of nEMoS, an All-in-One, Low-Cost, Web-Connected and 3D-Printed Device for Environmental Analysis

PubMed Central

Salamone, Francesco; Belussi, Lorenzo; Danza, Ludovico; Ghellere, Matteo; Meroni, Italo

2015-01-01

The Indoor Environmental Quality (IEQ) refers to the quality of the environment in relation to the health and well-being of the occupants. It is a holistic concept, which considers several categories, each related to a specific environmental parameter. This article describes a low-cost and open-source hardware architecture able to detect the indoor variables necessary for the IEQ calculation as an alternative to the traditional hardware used for this purpose. The system consists of some sensors and an Arduino board. One of the key strengths of Arduino is the possibility it affords of loading the script into the board’s memory and letting it run without interfacing with computers, thus granting complete independence, portability and accuracy. Recent works have demonstrated that the cost of scientific equipment can be reduced by applying open-source principles to their design using a combination of the Arduino platform and a 3D printer. The evolution of the 3D printer has provided a new means of open design capable of accelerating self-directed development. The proposed nano Environmental Monitoring System (nEMoS) instrument is shown to have good reliability and it provides the foundation for a more critical approach to the use of professional sensors as well as for conceiving new scenarios and potential applications. PMID:26053749

A novel essential domain perspective for exploring gene essentiality.

PubMed

Lu, Yao; Lu, Yulan; Deng, Jingyuan; Peng, Hai; Lu, Hui; Lu, Long Jason

2015-09-15

Genes with indispensable functions are identified as essential; however, the traditional gene-level studies of essentiality have several limitations. In this study, we characterized gene essentiality from a new perspective of protein domains, the independent structural or functional units of a polypeptide chain. To identify such essential domains, we have developed an Expectation-Maximization (EM) algorithm-based Essential Domain Prediction (EDP) Model. With simulated datasets, the model provided convergent results given different initial values and offered accurate predictions even with noise. We then applied the EDP model to six microbial species and predicted 1879 domains to be essential in at least one species, ranging 10-23% in each species. The predicted essential domains were more conserved than either non-essential domains or essential genes. Comparing essential domains in prokaryotes and eukaryotes revealed an evolutionary distance consistent with that inferred from ribosomal RNA. When utilizing these essential domains to reproduce the annotation of essential genes, we received accurate results that suggest protein domains are more basic units for the essentiality of genes. Furthermore, we presented several examples to illustrate how the combination of essential and non-essential domains can lead to genes with divergent essentiality. In summary, we have described the first systematic analysis on gene essentiality on the level of domains. huilu.bioinfo@gmail.com or Long.Lu@cchmc.org Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The New Youth Entrepreneur: Records and Books. Did You Make Any Money? Module 9.

ERIC Educational Resources Information Center

Kourilsky, Marilyn; And Others

The New Youth Entrepreneur curriculum is a series of 12 youth-oriented educational modules containing instructional materials, learning activities, and checkup exercises designed to teach students key elements of entrepreneurship. This document is the ninth module, and introduces students to recordkeeping and bookkeeping strategies essential for…

Hepatic tissue environment in NEMO-deficient mice critically regulates positive selection of donor cells after hepatocyte transplantation.

PubMed

Kaldenbach, Michaela; Cubero, Francisco Javier; Erschfeld, Stephanie; Liedtke, Christian; Trautwein, Christian; Streetz, Konrad

2014-01-01

Hepatocyte transplantation (HT) is a promising alternative treatment strategy for end-stage liver diseases compared with orthotopic liver transplantation. A limitation for this approach is the low engraftment of donor cells. The deletion of the I-kappa B kinase-regulatory subunit IKKγ/NEMO in hepatocytes prevents nuclear factor (NF)-kB activation and triggers spontaneous liver apoptosis, chronic hepatitis and the development of liver fibrosis and hepatocellular carcinoma. We hypothesized that NEMOΔhepa mice may therefore serve as an experimental model to study HT. Pre-conditioned NEMOΔhepa mice were transplanted with donor-hepatocytes from wildtype (WT) and mice deficient for the pro-apoptotic mediator Caspase-8 (Casp8Δhepa). Transplantation of isolated WT-hepatocytes into pre-conditioned NEMOΔhepa mice resulted in a 6-7 fold increase of donor cells 12 weeks after HT, while WT-recipients showed no liver repopulation. The use of apoptosis-resistant Casp8Δhepa-derived donor cells further enhanced the selection 3-fold after 12-weeks and up to 10-fold increase after 52 weeks compared with WT donors. While analysis of NEMOΔhepa mice revealed strong liver injury, HT-recipient NEMOΔhepa mice showed improved liver morphology and decrease in serum transaminases. Concomitant with these findings, the histological examination elicited an improved liver tissue architecture associated with significantly lower levels of apoptosis, decreased proliferation and a lesser amount of liver fibrogenesis. Altogether, our data clearly support the therapeutic benefit of the HT procedure into NEMOΔhepa mice. This study demonstrates the feasibility of the NEMOΔhepa mouse as an in vivo tool to study liver repopulation after HT. The improvement of the characteristic phenotype of chronic liver injury in NEMOΔhepa mice after HT suggests the therapeutic potential of HT in liver diseases with a chronic inflammatory phenotype and opens a new door for the applicability of this technique to

Hepatic Tissue Environment in NEMO-Deficient Mice Critically Regulates Positive Selection of Donor Cells after Hepatocyte Transplantation

PubMed Central

Kaldenbach, Michaela; Cubero, Francisco Javier; Erschfeld, Stephanie; Liedtke, Christian; Trautwein, Christian; Streetz, Konrad

2014-01-01

Background Hepatocyte transplantation (HT) is a promising alternative treatment strategy for end-stage liver diseases compared with orthotopic liver transplantation. A limitation for this approach is the low engraftment of donor cells. The deletion of the I-kappa B kinase-regulatory subunit IKKγ/NEMO in hepatocytes prevents nuclear factor (NF)-kB activation and triggers spontaneous liver apoptosis, chronic hepatitis and the development of liver fibrosis and hepatocellular carcinoma. We hypothesized that NEMOΔhepa mice may therefore serve as an experimental model to study HT. Methods Pre-conditioned NEMOΔhepa mice were transplanted with donor-hepatocytes from wildtype (WT) and mice deficient for the pro-apoptotic mediator Caspase-8 (Casp8Δhepa). Results Transplantation of isolated WT-hepatocytes into pre-conditioned NEMOΔhepa mice resulted in a 6-7 fold increase of donor cells 12 weeks after HT, while WT-recipients showed no liver repopulation. The use of apoptosis-resistant Casp8Δhepa-derived donor cells further enhanced the selection 3-fold after 12-weeks and up to 10-fold increase after 52 weeks compared with WT donors. While analysis of NEMOΔhepa mice revealed strong liver injury, HT-recipient NEMOΔhepa mice showed improved liver morphology and decrease in serum transaminases. Concomitant with these findings, the histological examination elicited an improved liver tissue architecture associated with significantly lower levels of apoptosis, decreased proliferation and a lesser amount of liver fibrogenesis. Altogether, our data clearly support the therapeutic benefit of the HT procedure into NEMOΔhepa mice. Conclusion This study demonstrates the feasibility of the NEMOΔhepa mouse as an in vivo tool to study liver repopulation after HT. The improvement of the characteristic phenotype of chronic liver injury in NEMOΔhepa mice after HT suggests the therapeutic potential of HT in liver diseases with a chronic inflammatory phenotype and opens a new door for

Naval EarthMap Observer: overview and data processing

NASA Astrophysics Data System (ADS)

Bowles, Jeffrey H.; Davis, Curtiss O.; Carney, Megan; Clamons, Dean; Gao, Bo-Cai; Gillis, David; Kappus, Mary E.; Lamela, G.; Montes, Marcos J.; Palmadesso, Peter J.; Rhea, J.; Snyder, William A.

1999-12-01

We present an overview of the Naval EarthMap Observer (NEMO) spacecraft and then focus on the processing of NEMO data both on-board the spacecraft and on the ground. The NEMO spacecraft provides for Joint Naval needs and demonstrates the use of hyperspectral imagery for the characterization of the littoral environment and for littoral ocean model development. NEMO is being funded jointly by the U.S. government and commercial partners. The Coastal Ocean Imaging Spectrometer (COIS) is the primary instrument on the NEMO and covers the spectral range from 400 to 2500 nm at 10-nm resolution with either 30 or 60 m work GSD. The hyperspectral data is processed on-board the NEMO using NRL's Optical Real-time Automated Spectral Identification System (ORASIS) algorithm that provides for real time analysis, feature extraction and greater than 10:1 data compression. The high compression factor allows for ground coverage of greater than 106 km2/day. Calibration of the sensor is done with a combination of moon imaging, using an onboard light source and vicarious calibration using a number of earth sites being monitored for that purpose. The data will be atmospherically corrected using ATREM. Algorithms will also be available to determine water clarity, bathymetry and bottom type.

Degree of bioresorbable vascular scaffold expansion modulates loss of essential function.

PubMed

Ferdous, Jahid; Kolachalama, Vijaya B; Kolandaivelu, Kumaran; Shazly, Tarek

2015-10-01

Drug-eluting bioresorbable vascular scaffolds (BVSs) have the potential to restore lumen patency, enable recovery of the native vascular environment, and circumvent late complications associated with permanent endovascular devices. To ensure therapeutic effects persist for sufficient times prior to scaffold resorption and resultant functional loss, many factors dictating BVS performance must be identified, characterized and optimized. While some factors relate to BVS design and manufacturing, others depend on device deployment and intrinsic vascular properties. Importantly, these factors interact and cannot be considered in isolation. The objective of this study is to quantify the extent to which degree of radial expansion modulates BVS performance, specifically in the context of modifying device erosion kinetics and evolution of structural mechanics and local drug elution. We systematically varied degree of radial expansion in model BVS constructs composed of poly dl-lactide-glycolide and generated in vitro metrics of device microstructure, degradation, erosion, mechanics and drug release. Experimental data permitted development of computational models that predicted transient concentrations of scaffold-derived soluble species and drug in the arterial wall, thus enabling speculation on the short- and long-term effects of differential expansion. We demonstrate that degree of expansion significantly affects scaffold properties critical to functionality, underscoring its relevance in BVS design and optimization. Bioresorbable vascular scaffold (BVS) therapy is beginning to transform the treatment of obstructive artery disease, owing to effective treatment of short term vessel closure while avoiding long term consequences such as in situ, late stent thrombosis - a fatal event associated with permanent implants such as drug-eluting stents. As device scaffolding and drug elution are temporary for BVS, the notion of using this therapy in lieu of existing, clinically

A Comparative Study on Selective PPAR Modulators through Quantitative Structure-activity Relationship, Pharmacophore and Docking Analyses.

PubMed

Nandy, Ashis; Roy, Kunal; Saha, Achintya

2018-01-01

Metabolic syndrome is a matrix of different metabolic disorders which are the leading cause of death in human beings. Peroxysome proliferated activated receptor (PPAR) is a nuclear receptor involved in metabolism of fats and glucose. In order to explore structural requirements for selective PPAR modulators to control lipid and carbohydrate metabolism, the multi-cheminformatics studies have been performed. In silico modeling studies have been performed on a diverse set of PPAR modulators through quantitative structure-activity relationship (QSAR), pharmacophore mapping and docking studies. It is observed that the presence of an amide fragment (-CONHRPh) has a detrimental effect while an aliphatic ether linkage has a beneficial effect on PPARα modulation. On the other hand, the presence of an amide fragment has a positive effect on PPARδ modulation, but the aliphatic ether linkage and substituted aromatic ring in the molecular scaffold are very much essential for imparting potent and selective PPARγ modulation. Negative ionizable features (i.e. polar fragments) must be present in PPARδ and α modulators, but a hydrophobic feature is the prime requirement for PPARγ modulation. Here, the essential structural features have been explored for selective modulation of each subtype of PPAR in order to design new modulators with improved activity/selectivity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The influence of essential oils on human vigilance.

PubMed

Heuberger, Eva; Ilmberger, Josef

2010-09-01

Olfactory stimuli are used in aromatherapy to enhance mood, well-being and work efficiency. Nevertheless, the impact of fragrances on cognitive performance in humans is not well understood. The present investigation aimed to evaluate the effects of 1,8-cineol, jasmine absolute ether, linalyl acetate and peppermint essential oil on human vigilance performance. The odorants were administered by means of inhalation and, except for peppermint essential oil, were tested at 2 different dosages. Performance in a standard visual vigilance task was measured in terms of speed and accuracy and subjective ratings of the odorants were assessed in terms of pleasantness, intensity, arousal and stress. We hypothesized that 1,8-cineol, jasmine absolute ether and peppermint essential oil would improve vigilance performance, whereas linalyl acetate would impair such performance. Comparison of the performances of the seven independent experimental groups with that of a control group did not show any of the expected effects. In contrast, inhalation of linalyl acetate decreased reaction times. Within-group analyses, however, revealed significant interactions between subjective ratings of the odorants and task performance. The results of the present investigation emphasize the high impact of subjective factors on the modulation of attentional functions by olfactory stimuli in humans.

Traffic-Light-Preemption Vehicle-Transponder Software Module

NASA Technical Reports Server (NTRS)

Bachelder, Aaron; Foster, Conrad

2005-01-01

A prototype wireless data-communication and control system automatically modifies the switching of traffic lights to give priority to emergency vehicles. The system, which was reported in several NASA Tech Briefs articles at earlier stages of development, includes a transponder on each emergency vehicle, a monitoring and control unit (an intersection controller) at each intersection equipped with traffic lights, and a central monitoring subsystem. An essential component of the system is a software module executed by a microcontroller in each transponder. This module integrates and broadcasts data on the position, velocity, acceleration, and emergency status of the vehicle. The position, velocity, and acceleration data are derived partly from the Global Positioning System, partly from deductive reckoning, and partly from a diagnostic computer aboard the vehicle. The software module also monitors similar broadcasts from other vehicles and from intersection controllers, informs the driver of which intersections it controls, and generates visible and audible alerts to inform the driver of any other emergency vehicles that are close enough to create a potential hazard. The execution of the software module can be monitored remotely and the module can be upgraded remotely and, hence, automatically

Commensal bacteria and essential amino acids control food choice behavior and reproduction

PubMed Central

Fioreze, Gabriela Tondolo; Anjos, Margarida; Baltazar, Célia; Elias, Ana Paula; Itskov, Pavel M.; Piper, Matthew D. W.

2017-01-01

Choosing the right nutrients to consume is essential to health and wellbeing across species. However, the factors that influence these decisions are poorly understood. This is particularly true for dietary proteins, which are important determinants of lifespan and reproduction. We show that in Drosophila melanogaster, essential amino acids (eAAs) and the concerted action of the commensal bacteria Acetobacter pomorum and Lactobacilli are critical modulators of food choice. Using a chemically defined diet, we show that the absence of any single eAA from the diet is sufficient to elicit specific appetites for amino acid (AA)-rich food. Furthermore, commensal bacteria buffer the animal from the lack of dietary eAAs: both increased yeast appetite and decreased reproduction induced by eAA deprivation are rescued by the presence of commensals. Surprisingly, these effects do not seem to be due to changes in AA titers, suggesting that gut bacteria act through a different mechanism to change behavior and reproduction. Thus, eAAs and commensal bacteria are potent modulators of feeding decisions and reproductive output. This demonstrates how the interaction of specific nutrients with the microbiome can shape behavioral decisions and life history traits. PMID:28441450

Commensal bacteria and essential amino acids control food choice behavior and reproduction.

PubMed

Leitão-Gonçalves, Ricardo; Carvalho-Santos, Zita; Francisco, Ana Patrícia; Fioreze, Gabriela Tondolo; Anjos, Margarida; Baltazar, Célia; Elias, Ana Paula; Itskov, Pavel M; Piper, Matthew D W; Ribeiro, Carlos

2017-04-01

Choosing the right nutrients to consume is essential to health and wellbeing across species. However, the factors that influence these decisions are poorly understood. This is particularly true for dietary proteins, which are important determinants of lifespan and reproduction. We show that in Drosophila melanogaster, essential amino acids (eAAs) and the concerted action of the commensal bacteria Acetobacter pomorum and Lactobacilli are critical modulators of food choice. Using a chemically defined diet, we show that the absence of any single eAA from the diet is sufficient to elicit specific appetites for amino acid (AA)-rich food. Furthermore, commensal bacteria buffer the animal from the lack of dietary eAAs: both increased yeast appetite and decreased reproduction induced by eAA deprivation are rescued by the presence of commensals. Surprisingly, these effects do not seem to be due to changes in AA titers, suggesting that gut bacteria act through a different mechanism to change behavior and reproduction. Thus, eAAs and commensal bacteria are potent modulators of feeding decisions and reproductive output. This demonstrates how the interaction of specific nutrients with the microbiome can shape behavioral decisions and life history traits.

Bergamot Essential Oil Attenuates Anxiety-Like Behaviour in Rats.

PubMed

Rombolà, Laura; Tridico, Laura; Scuteri, Damiana; Sakurada, Tsukasa; Sakurada, Shinobu; Mizoguchi, Hirokazu; Avato, Pinarosa; Corasaniti, Maria Tiziana; Bagetta, Giacinto; Morrone, Luigi Antonio

2017-04-11

Preclinical studies have recently highlighted that bergamot essential oil (BEO) is endowed with remarkable neurobiolological effects. BEO can affect synaptic transmission, modulate electroencephalographic activity and it showed neuroprotective and analgesic properties. The phytocomplex, along with other essential oils, is also widely used in aromatherapy to minimize symptoms of stress-induced anxiety and mild mood disorders. However, only limited preclinical evidences are actually available. This study examined the anxiolytic/sedative-like effects of BEO using an open field task (OFT), an elevated plus-maze task (EPM), and a forced swimming task (FST) in rats. This study further compared behavioural effects of BEO to those of the benzodiazepine diazepam. Analysis of data suggests that BEO induces anxiolytic-like/relaxant effects in animal behavioural tasks not superimposable to those of the DZP. The present observations provide further insight to the pharmacological profile of BEO and support its rational use in aromatherapy.

Antimicrobial activity of commercially available essential oils against Streptococcus mutans.

PubMed

Chaudhari, Lalit Kumar D; Jawale, Bhushan Arun; Sharma, Sheeba; Sharma, Hemant; Kumar, C D Mounesh; Kulkarni, Pooja Adwait

2012-01-01

Many essential oils have been advocated for use in complementary medicine for bacterial and fungal infections. However, few of the many claims of therapeutic efficacy have been validated adequately by either in vitro testing or in vivo clinical trials. To study the antibacterial activity of nine commercially available essential oils against Streptococcus mutans in vitro and to compare the antibacterial activity between each material. Nine pure essential oils; wintergreen oil, lime oil, cinnamon oil, spearmint oil, peppermint oil, lemongrass oil, cedarwood oil, clove oil and eucalyptus oil were selected for the study. Streptococcus mutans was inoculated at 37ºC and seeded on blood agar medium. Agar well diffusion assay was used to measure antibacterial activity. Zone of inhibition was measured around the filter paper in millimeters with vernier caliper. Cinnamon oil showed highest activity against Streptococcus mutans followed by lemongrass oil and cedarwood oil. Wintergreen oil, lime oil, peppermint oil and spearmint oil showed no antibacterial activity. Cinnamon oil, lemongrass oil, cedarwood oil, clove oil and eucalyptus oil exhibit antibacterial property against S. mutans. The use of these essential oils against S. mutans can be a viable alternative to other antibacterial agents as these are an effective module used in the control of both bacteria and yeasts responsible for oral infections.

Efficient Mobility Management Signalling in Network Mobility Supported PMIPV6

PubMed Central

Jebaseeli Samuelraj, Ananthi; Jayapal, Sundararajan

2015-01-01

Proxy Mobile IPV6 (PMIPV6) is a network based mobility management protocol which supports node's mobility without the contribution from the respective mobile node. PMIPV6 is initially designed to support individual node mobility and it should be enhanced to support mobile network movement. NEMO-BSP is an existing protocol to support network mobility (NEMO) in PMIPV6 network. Due to the underlying differences in basic protocols, NEMO-BSP cannot be directly applied to PMIPV6 network. Mobility management signaling and data structures used for individual node's mobility should be modified to support group nodes' mobility management efficiently. Though a lot of research work is in progress to implement mobile network movement in PMIPV6, it is not yet standardized and each suffers with different shortcomings. This research work proposes modifications in NEMO-BSP and PMIPV6 to achieve NEMO support in PMIPV6. It mainly concentrates on optimizing the number and size of mobility signaling exchanged while mobile network or mobile network node changes its access point. PMID:26366431

Efficient Mobility Management Signalling in Network Mobility Supported PMIPV6.

PubMed

Samuelraj, Ananthi Jebaseeli; Jayapal, Sundararajan

2015-01-01

Proxy Mobile IPV6 (PMIPV6) is a network based mobility management protocol which supports node's mobility without the contribution from the respective mobile node. PMIPV6 is initially designed to support individual node mobility and it should be enhanced to support mobile network movement. NEMO-BSP is an existing protocol to support network mobility (NEMO) in PMIPV6 network. Due to the underlying differences in basic protocols, NEMO-BSP cannot be directly applied to PMIPV6 network. Mobility management signaling and data structures used for individual node's mobility should be modified to support group nodes' mobility management efficiently. Though a lot of research work is in progress to implement mobile network movement in PMIPV6, it is not yet standardized and each suffers with different shortcomings. This research work proposes modifications in NEMO-BSP and PMIPV6 to achieve NEMO support in PMIPV6. It mainly concentrates on optimizing the number and size of mobility signaling exchanged while mobile network or mobile network node changes its access point.

Preisocalamendiol, Shyobunol and Related Oxygenated Sesquiterpenes from Bolivian Schinus molle Essential Oil.

PubMed

St-Gelais, Alexis; Mathieu, Michel; Levasseur, Virginie; Ovando, Jesús Flores; Escamilla, Ruben; Marceau, Hubert

2016-04-01

Five batches of Bolivian Schinus molle essential oils were obtained from pilot and industrial-scale hydrodiffusions. They were analyzed by gas chromatography to find 80 known compounds and two unknown molecules. In particular, preisocalamendiol (5.6-11.0 %) was found to be an important constituent of these oils, along with shyobunol (0.6-3.2 %) and several other related oxygenated sesquiterpenes. These compounds, usually found in Acorus calamus, had not been reported altogether in S. molle essential oils previously. These findings, in light of the GABAA positive modulating effect of shyobunone and preisocalamendiol, along with some traditional uses of S. molle, suggest that further investigation of the tranquilizing properties of these Bolivian oils would be of interest.

Reduced SHARPIN and LUBAC Formation May Contribute to CCl₄- or Acetaminophen-Induced Liver Cirrhosis in Mice.

PubMed

Yamamotoya, Takeshi; Nakatsu, Yusuke; Matsunaga, Yasuka; Fukushima, Toshiaki; Yamazaki, Hiroki; Kaneko, Sunao; Fujishiro, Midori; Kikuchi, Takako; Kushiyama, Akifumi; Tokunaga, Fuminori; Asano, Tomoichiro; Sakoda, Hideyuki

2017-02-04

Linear ubiquitin chain assembly complex (LUBAC), composed of SHARPIN (SHANK-associated RH domain-interacting protein), HOIL-1L (longer isoform of heme-oxidized iron-regulatory protein 2 ubiquitin ligase-1), and HOIP (HOIL-1L interacting protein), forms linear ubiquitin on nuclear factor-κB (NF-κB) essential modulator (NEMO) and induces NF-κB pathway activation. SHARPIN expression and LUBAC formation were significantly reduced in the livers of mice 24 h after the injection of either carbon tetrachloride (CCl₄) or acetaminophen (APAP), both of which produced the fulminant hepatitis phenotype. To elucidate its pathological significance, hepatic SHARPIN expression was suppressed in mice by injecting shRNA adenovirus via the tail vein. Seven days after this transduction, without additional inflammatory stimuli, substantial inflammation and fibrosis with enhanced hepatocyte apoptosis occurred in the livers. A similar but more severe phenotype was observed with suppression of HOIP, which is responsible for the E3 ligase activity of LUBAC. Furthermore, in good agreement with these in vivo results, transduction of Hepa1-6 hepatoma cells with SHARPIN, HOIL-1L, or HOIP shRNA adenovirus induced apoptosis of these cells in response to tumor necrosis factor-α (TNFα) stimulation. Thus, LUBAC is essential for the survival of hepatocytes, and it is likely that reduction of LUBAC is a factor promoting hepatocyte death in addition to the direct effect of drug toxicity.

Enantioselective comprehensive two-dimensional gas chromatography of lavender essential oil.

PubMed

Krupčík, Ján; Gorovenko, Roman; Špánik, Ivan; Armstrong, Daniel W; Sandra, Pat

2016-12-01

The enantiomeric composition of several chiral markers in lavender essential oil was studied by flow modulated comprehensive two-dimensional gas chromatography operated in the reverse flow mode and hyphenated to flame ionization and quadrupole mass spectrometric detection. Two capillary column series were used in this study, 2,3-di-O-ethyl-6-O-tert-butyldimethylsilyl-β-cyclodextrin or 2,3,6-tri-O-methyl-β-cyclodextrin, as the chiral column in the first dimension and α polyethylene glycol column in the second dimension. Combining the chromatographic data obtained on these column series, the enantiomeric and excess ratios for α-pinene, β-pinene, camphor, lavandulol, borneol, and terpinen-4-ol were determined. This maybe a possible route to assess the authenticity of lavender essential oil. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Macrogenomic engineering via modulation of the scaling of chromatin packing density.

PubMed

Almassalha, Luay M; Bauer, Greta M; Wu, Wenli; Cherkezyan, Lusik; Zhang, Di; Kendra, Alexis; Gladstein, Scott; Chandler, John E; VanDerway, David; Seagle, Brandon-Luke L; Ugolkov, Andrey; Billadeau, Daniel D; O'Halloran, Thomas V; Mazar, Andrew P; Roy, Hemant K; Szleifer, Igal; Shahabi, Shohreh; Backman, Vadim

2017-11-01

Many human diseases result from the dysregulation of the complex interactions between tens to thousands of genes. However, approaches for the transcriptional modulation of many genes simultaneously in a predictive manner are lacking. Here, through the combination of simulations, systems modelling and in vitro experiments, we provide a physical regulatory framework based on chromatin packing-density heterogeneity for modulating the genomic information space. Because transcriptional interactions are essentially chemical reactions, they depend largely on the local physical nanoenvironment. We show that the regulation of the chromatin nanoenvironment allows for the predictable modulation of global patterns in gene expression. In particular, we show that the rational modulation of chromatin density fluctuations can lead to a decrease in global transcriptional activity and intercellular transcriptional heterogeneity in cancer cells during chemotherapeutic responses to achieve near-complete cancer cell killing in vitro. Our findings represent a 'macrogenomic engineering' approach to modulating the physical structure of chromatin for whole-scale transcriptional modulation.

An Introductory Review Module For an Anti-Infectives Therapeutics Course

PubMed Central

Murphy, Kendrick; Zaeem, Maryam; DiVall, Margarita V.

2012-01-01

Objective. To determine whether an introductory review module using a hybrid-learning approach helped students learn infectious disease management in an anti-infectives therapeutics course. Design. An introductory module consisting of an online pharmacology review, pre-class assignment, 2 classroom lectures, and 1 case-based lecture was developed and implemented. Assessment. Among the 110 students who completed pre- and post-tests on the material covered, average scores increased from 71% to 83% (p<0.0001). Performance on knowledge-based question improved for 8 out of 10 questions (p<0.05) and student confidence increased from the first lecture to completion of the module (p<0.001 for all comparisons). Of the 129 students who completed an evaluation of the introductory module, 98% strongly agreed or agreed that the content was essential for course success. Conclusion. The addition of an introductory module using a hybrid-learning approach to review and solidify concepts of medical microbiology and pharmacology provided the foundation necessary for success in an infectious diseases module. PMID:23049107

Asparagine, valine, and threonine in the third extracellular loop of muscarinic receptor have essential roles in the positive cooperativity of strychnine-like allosteric modulators.

PubMed

Jakubík, J; Krejcí, A; Dolezal, V

2005-05-01

We have investigated allosteric interactions of four closely related strychnine-like substances: Wieland-Gumlich aldehyde (WGA), propargyl Wieland-Gumlich aldehyde, strychnine, and brucine with N-methylscopolamine (NMS) on M(3) subtype of muscarinic receptor genetically modified in the second or the third extracellular loop to corresponding loops of M(2) subtype (M(3)o2 and M(3)o3 chimera). The M(3)o2 chimeric receptor The exhibited no change in either affinity of strychnine, brucine, and WGA or in cooperativity of brucine or WGA, whereas both parameters for propargyl-WGA changed. In contrast, there was a change in affinity of all tested modulators (except for brucine) and in their cooperativity in the M(3)o3 chimera. Directions of affinity changes in both chimeras were always toward values of the donor M(2) subtype, but changes in cooperativity were variable. Compared with the native M(3) receptor, strychnine displayed a slight increase in positive cooperativity and propargyl-WGA a robust decrease in negative cooperativity at M(3)o2 chimera. Similar changes were found in the M(3)o3 chimera. Interestingly, cooperativity of brucine and WGA at the M(3)o3 chimera changed from negative to positive. This is the first evidence of constitution of positive cooperativity of WGA by switching sequences of two parental receptors, both exhibiting negative cooperativity. Gradual replacement of individual amino acids revealed that only three residues (NVT of the o3 loop of the M(2) receptor) are involved in this effect. Data suggest that these amino acids are essential for propagation of a conformation change resulting in positive cooperativity induced by these modulators.

Interleukin 10 is an essential modulator of mucoid metaplasia in a mouse otitis media model

PubMed Central

Tsuchiya, Katsuyuki; Komori, Masahiro; Zheng, Qing Yin; Ferrieri, Patricia; Lin, Jizhen

2009-01-01

Inflammatory cytokines are involved in the development of mucus cell metaplasia/hyperplasia (MCM) in otitis media (OM). However, which cytokines play an essential role in MCM OM is not clear at the moment. In this study, we hypothesized that interleukin-10 (IL-10) played an indispensable role in MCM of bacterial OM and used IL-10 knockout mice to test this hypothesis. In wild-type mice, both S. pneumoniae and H. influenzae triggered the development of MCM in the middle ear mucosa. In IL-10 knockout mice, the number of goblet cells and mucin-producing cells in the middle ear was significantly reduced after bacterial middle ear infection compared with that in wild-type mice. We, therefore, concluded that IL-10 plays an essential role in MCM of bacterial OM. IL-10 is a potential target for the treatment of MCM in OM. PMID:18771082

Investigation of active volcanic areas through oceanographic data collected by the NEMO-SN1 multiparametric seafloor observatory

NASA Astrophysics Data System (ADS)

Lo Bue, Nadia; Sgroi, Tiziana; Giovanetti, Gabriele; Marinaro, Giuditta; Embriaco, Davide; Beranzoli, Laura; Favali, Paolo

2015-04-01

In the framework of the European Research Infrastructure EMSO (European Multidisciplinary Seafloor and water-column Observatory, www.emso-eu.org), the cabled multidisciplinary seafloor observatory node NEMO-SN1 was deployed in the Western Ionian Sea (Southern Italy) at a depth of 2100 m, about 25 km off-shore Eastern Sicily, close to the Mt. Etna volcano system. The oceanographic payload mounted on this observatory was originally designed to monitor possible variations of the local hydrodynamic playing a crucial role on the redistribution of deep water in the Eastern Mediterranean Sea. In particular the Acoustic Doppler Current Profiler (ADCP RDI WorkHorse 600 kHz) was configured with the main aim to record the bottom dynamics, watching few meters of water column above the station (about 30 m). Surprisingly, this sensor offered a spectacular recording of the Mt.Etna pyroclastic activity occurred on 2013 which affected the ESE sector of the volcano. Although the ADCP sensor is commonly used to measure speed and direction of sea currents, it is more often used to monitor concentration suspended matter of controlled areas, such as rivers or coastal marine environments, by the analysis of the acoustic backscatter intensity. This standard condition entails some a-priori knowledge (i.e. suspended sediment concentration, particle size, echo intensity calibration) useful to well configure the sensors before starting its acquisition. However, in the case of Mt. Etna pyroclastic activity, due to the unexpected recording, these information were not available and it was necessary to work in a post-processing mode considering all acquired data. In fact, several different parameters contribute to complete the comprehension of the observed phenomenon: the ADCP acoustic wavelength able to indirectly provide information on the detectable particle size, the intensity of the explosive activity useful to define the starting energy of the volcanic system, the oceanographic local

Gene therapy decreases seizures in a model of Incontinentia pigmenti.

PubMed

Dogbevia, Godwin K; Töllner, Kathrin; Körbelin, Jakob; Bröer, Sonja; Ridder, Dirk A; Grasshoff, Hanna; Brandt, Claudia; Wenzel, Jan; Straub, Beate K; Trepel, Martin; Löscher, Wolfgang; Schwaninger, Markus

2017-07-01

Incontinentia pigmenti (IP) is a genetic disease leading to severe neurological symptoms, such as epileptic seizures, but no specific treatment is available. IP is caused by pathogenic variants that inactivate the Nemo gene. Replacing Nemo through gene therapy might provide therapeutic benefits. In a mouse model of IP, we administered a single intravenous dose of the adeno-associated virus (AAV) vector, AAV-BR1-CAG-NEMO, delivering the Nemo gene to the brain endothelium. Spontaneous epileptic seizures and the integrity of the blood-brain barrier (BBB) were monitored. The endothelium-targeted gene therapy improved the integrity of the BBB. In parallel, it reduced the incidence of seizures and delayed their occurrence. Neonate mice intravenously injected with the AAV-BR1-CAG-NEMO vector developed no hepatocellular carcinoma or other major adverse effects 11 months after vector injection, demonstrating that the vector has a favorable safety profile. The data show that the BBB is a target of antiepileptic treatment and, more specifically, provide evidence for the therapeutic benefit of a brain endothelial-targeted gene therapy in IP. Ann Neurol 2017;82:93-104. © 2017 American Neurological Association.

Cas9 Nickase-Assisted RNA Repression Enables Stable and Efficient Manipulation of Essential Metabolic Genes in Clostridium cellulolyticum.

PubMed

Xu, Tao; Li, Yongchao; He, Zhili; Van Nostrand, Joy D; Zhou, Jizhong

2017-01-01

Essential gene functions remain largely underexplored in bacteria. Clostridium cellulolyticum is a promising candidate for consolidated bioprocessing; however, its genetic manipulation to reduce the formation of less-valuable acetate is technically challenging due to the essentiality of acetate-producing genes. Here we developed a Cas9 nickase-assisted chromosome-based RNA repression to stably manipulate essential genes in C. cellulolyticum . Our plasmid-based expression of antisense RNA (asRNA) molecules targeting the phosphotransacetylase ( pta ) gene successfully reduced the enzymatic activity by 35% in cellobiose-grown cells, metabolically decreased the acetate titer by 15 and 52% in wildtype transformants on cellulose and xylan, respectively. To control both acetate and lactate simultaneously, we transformed the repression plasmid into lactate production-deficient mutant and found the plasmid delivery reduced acetate titer by more than 33%, concomitant with negligible lactate formation. The strains with pta gene repression generally diverted more carbon into ethanol. However, further testing on chromosomal integrants that were created by double-crossover recombination exhibited only very weak repression because DNA integration dramatically lessened gene dosage. With the design of a tandem repetitive promoter-driven asRNA module and the use of a new Cas9 nickase genome editing tool, a chromosomal integrant (LM3P) was generated in a single step and successfully enhanced RNA repression, with a 27% decrease in acetate titer on cellulose in antibiotic-free medium. These results indicate the effectiveness of tandem promoter-driven RNA repression modules in promoting gene repression in chromosomal integrants. Our combinatorial method using a Cas9 nickase genome editing tool to integrate the gene repression module demonstrates easy-to-use and high-efficiency advantages, paving the way for stably manipulating genes, even essential ones, for functional characterization

Cas9 Nickase-Assisted RNA Repression Enables Stable and Efficient Manipulation of Essential Metabolic Genes in Clostridium cellulolyticum

PubMed Central

Xu, Tao; Li, Yongchao; He, Zhili; Van Nostrand, Joy D.; Zhou, Jizhong

2017-01-01

Essential gene functions remain largely underexplored in bacteria. Clostridium cellulolyticum is a promising candidate for consolidated bioprocessing; however, its genetic manipulation to reduce the formation of less-valuable acetate is technically challenging due to the essentiality of acetate-producing genes. Here we developed a Cas9 nickase-assisted chromosome-based RNA repression to stably manipulate essential genes in C. cellulolyticum. Our plasmid-based expression of antisense RNA (asRNA) molecules targeting the phosphotransacetylase (pta) gene successfully reduced the enzymatic activity by 35% in cellobiose-grown cells, metabolically decreased the acetate titer by 15 and 52% in wildtype transformants on cellulose and xylan, respectively. To control both acetate and lactate simultaneously, we transformed the repression plasmid into lactate production-deficient mutant and found the plasmid delivery reduced acetate titer by more than 33%, concomitant with negligible lactate formation. The strains with pta gene repression generally diverted more carbon into ethanol. However, further testing on chromosomal integrants that were created by double-crossover recombination exhibited only very weak repression because DNA integration dramatically lessened gene dosage. With the design of a tandem repetitive promoter-driven asRNA module and the use of a new Cas9 nickase genome editing tool, a chromosomal integrant (LM3P) was generated in a single step and successfully enhanced RNA repression, with a 27% decrease in acetate titer on cellulose in antibiotic-free medium. These results indicate the effectiveness of tandem promoter-driven RNA repression modules in promoting gene repression in chromosomal integrants. Our combinatorial method using a Cas9 nickase genome editing tool to integrate the gene repression module demonstrates easy-to-use and high-efficiency advantages, paving the way for stably manipulating genes, even essential ones, for functional characterization and

Neuroimaging essentials in essential tremor: A systematic review

PubMed Central

Sharifi, Sarvi; Nederveen, Aart J.; Booij, Jan; van Rootselaar, Anne-Fleur

2014-01-01

Background Essential tremor is regarded to be a disease of the central nervous system. Neuroimaging is a rapidly growing field with potential benefits to both diagnostics and research. The exact role of imaging techniques with respect to essential tremor in research and clinical practice is not clear. A systematic review of the different imaging techniques in essential tremor is lacking in the literature. Methods We performed a systematic literature search combining the terms essential tremor and familial tremor with the following keywords: imaging, MRI, VBM, DWI, fMRI, PET and SPECT, both in abbreviated form as well as in full form. We summarize and discuss the quality and the external validity of each study and place the results in the context of existing knowledge regarding the pathophysiology of essential tremor. Results A total of 48 neuroimaging studies met our search criteria, roughly divided into 19 structural and 29 functional and metabolic studies. The quality of the studies varied, especially concerning inclusion criteria. Functional imaging studies indicated cerebellar hyperactivity during rest and during tremor. The studies also pointed to the involvement of the thalamus, the inferior olive and the red nucleus. Structural studies showed less consistent results. Discussion and conclusion Neuroimaging techniques in essential tremor give insight into the pathophysiology of essential tremor indicating the involvement of the cerebellum as the most consistent finding. GABAergic dysfunction might be a major premise in the pathophysiological hypotheses. Inconsistencies between studies can be partly explained by the inclusion of heterogeneous patient groups. Improvement of scientific research requires more stringent inclusion criteria and application of advanced analysis techniques. Also, the use of multimodal neuroimaging techniques is a promising development in movement disorders research. Currently, the role of imaging techniques in essential tremor in daily

Computational nanoelectronics towards: design, analysis, synthesis, and fundamental limits

NASA Technical Reports Server (NTRS)

Klimeck, G.

2003-01-01

This seminar will review the development of a comprehensive nanoelectronic modeling tool (NEMO 1-D and NEMO 3-D) and its application to high-speed electronics (resonant tunneling diodes) and IR detectors and lasers (quantum dots and 1-D heterostructures).

Essential role of UCP1 modulating the central effects of thyroid hormones on energy balance

PubMed Central

Alvarez-Crespo, Mayte; Csikasz, Robert I.; Martínez-Sánchez, Noelia; Diéguez, Carlos; Cannon, Barbara; Nedergaard, Jan; López, Miguel

2016-01-01

Objective Classically, metabolic effects of thyroid hormones (THs) have been considered to be peripherally mediated, i.e. different tissues in the body respond directly to thyroid hormones with an increased metabolism. An alternative view is that the metabolic effects are centrally regulated. We have examined here the degree to which prolonged, centrally infused triiodothyronine (T3) could in itself induce total body metabolic effects and the degree to which brown adipose tissue (BAT) thermogenesis was essential for such effects, by examining uncoupling protein 1 (UCP1) KO mice. Methods Wildtype and UPC1 KO mice were centrally-treated with T3 by using minipumps. Metabolic measurements were analyzed by indirect calorimetry and expression analysis by RT-PCR or western blot. BAT morphology and histology were studied by immunohistochemistry. Results We found that central T3-treatment led to reduced levels of hypothalamic AMP-activated protein kinase (AMPK) and elevated body temperature (0.7 °C). UCP1 was essential for the T3-induced increased rate of energy expenditure, which was only observable at thermoneutrality and notably only during the active phase, for the increased body weight loss, for the increased hypothalamic levels of neuropeptide Y (NPY) and agouti-related peptide (AgRP) and for the increased food intake induced by central T3-treatment. Prolonged central T3-treatment also led to recruitment of BAT and britening/beiging (“browning”) of inguinal white adipose tissue (iWAT). Conclusions We conclude that UCP1 is essential for mediation of the central effects of thyroid hormones on energy balance, and we suggest that similar UCP1-dependent effects may underlie central energy balance effects of other agents. PMID:27069867

microRNA-221 Enhances MYCN via Targeting Nemo-like Kinase and Functions as an Oncogene Related to Poor Prognosis in Neuroblastoma.

PubMed

He, Xiao-Yan; Tan, Zheng-Lan; Mou, Qin; Liu, Fang-Jie; Liu, Shan; Yu, Chao-Wen; Zhu, Jin; Lv, Lin-Ya; Zhang, Jun; Wang, Shan; Bao, Li-Ming; Peng, Bin; Zhao, Hui; Zou, Lin

2017-06-01

Purpose: MYCN is one of the most well-characterized genetic markers of neuroblastoma. However, the mechanisms as to how MYCN mediate neuroblastoma tumorigenesis are not fully clear. Increasing evidence has confirmed that the dysregulation of miRNAs is involved in MYCN-mediated neuroblastoma tumorigenesis, supporting their potential as therapeutic targets for neuroblastoma. Although miR-221 has been reported as one of the upregulated miRNAs, the interplay between miR-221 and MYCN-mediated neuroblastoma progression remains largely elusive. Experimental Design: The expression of miR-221 in the formalin-fixed, paraffin-embedded tissues from 31 confirmed patients with neuroblastoma was detected by locked nucleic acid- in situ hybridization and qRT-PCR. The correlation between miR-221 expression and clinical features in patients with neuroblastoma was assessed. The mechanisms as to how miR-221 regulate MYCN in neuroblastoma were addressed. The effect of miR-221 on cellular proliferation in neuroblastoma was determined both in vitro and in vivo Results: miR-221 was significantly upregulated in neuroblastoma tumor cells and tissues that overexpress MYCN, and high expression of miR-221 was positively associated with poor survival in patients with neuroblastoma. Nemo-like kinase (NLK) as a direct target of miR-221 in neuroblastoma was verified. In addition, overexpression of miR-221 decreased LEF1 phosphorylation but increased the expression of MYCN via targeting of NLK and further regulated cell cycle, particularly in S-phase, promoting the growth of neuroblastoma cells. Conclusions: This study provides a novel insight for miR-221 in the control of neuroblastoma cell proliferation and tumorigenesis, suggesting potentials of miR-221 as a prognosis marker and therapeutic target for patients with MYCN overexpressing neuroblastoma. Clin Cancer Res; 23(11); 2905-18. ©2016 AACR . ©2016 American Association for Cancer Research.

Transcription factor genes essential for cell proliferation and replicative lifespan in budding yeast

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

Kamei, Yuka; Tai, Akiko; Dakeyama, Shota

Many of the lifespan-related genes have been identified in eukaryotes ranging from the yeast to human. However, there is limited information available on the longevity genes that are essential for cell proliferation. Here, we investigated whether the essential genes encoding DNA-binding transcription factors modulated the replicative lifespan of Saccharomyces cerevisiae. Heterozygous diploid knockout strains for FHL1, RAP1, REB1, and MCM1 genes showed significantly short lifespan. {sup 1}H-nuclear magnetic resonance analysis indicated a characteristic metabolic profile in the Δfhl1/FHL1 mutant. These results strongly suggest that FHL1 regulates the transcription of lifespan related metabolic genes. Thus, heterozygous knockout strains could be themore » potential materials for discovering further novel lifespan genes. - Highlights: • Involvement of yeast TF genes essential for cell growth in lifespan was evaluated. • The essential TF genes, FHL1, RAP1, REB1, and MCM1, regulate replicative lifespan. • Heterozygous deletion of FHL1 changes cellular metabolism related to lifespan.« less

Modified Dual Three-Pulse Modulation technique for single-phase inverter topology

NASA Astrophysics Data System (ADS)

Sree Harsha, N. R.; Anitha, G. S.; Sreedevi, A.

2016-01-01

In a recent paper, a new modulation technique called Dual Three Pulse Modulation (DTPM) was proposed to improve the efficiency of the power converters of the Electric/Hybrid/Fuel-cell vehicles. It was simulated in PSIM 9.0.4 and uses analog multiplexers to generate the modulating signals for the DC/DC converter and inverter. The circuit used is complex and many other simulation softwares do not support the analog multiplexers as well. Also, the DTPM technique produces modulating signals for the converter, which are essentially needed to produce the modulating signals for the inverter. Hence, it cannot be used efficiently to switch the valves of a stand-alone inverter. We propose a new method to generate the modulating signals to switch MOSFETs of a single phase Dual-Three pulse Modulation based stand-alone inverter. The circuits proposed are simulated in Multisim 12.0. We also show an alternate way to switch a DC/DC converter in a way depicted by DTPM technique both in simulation (MATLAB/Simulink) and hardware. The circuitry is relatively simple and can be used for the further investigations of DTPM technique.

Analyzing Pulse-Code Modulation On A Small Computer

NASA Technical Reports Server (NTRS)

Massey, David E.

1988-01-01

System for analysis pulse-code modulation (PCM) comprises personal computer, computer program, and peripheral interface adapter on circuit board that plugs into expansion bus of computer. Functions essentially as "snapshot" PCM decommutator, which accepts and stores thousands of frames of PCM data, sifts through them repeatedly to process according to routines specified by operator. Enables faster testing and involves less equipment than older testing systems.

Essential role of integrin-linked kinase in regulation of phagocytosis in keratinocytes.

PubMed

Sayedyahossein, Samar; Nini, Lylia; Irvine, Timothy S; Dagnino, Lina

2012-10-01

Phagocytic melanosome uptake by epidermal keratinocytes is a central protective mechanism against damage induced by ultraviolet radiation. Phagocytosis requires formation of pseudopodia via actin cytoskeleton rearrangements. Integrin-linked kinase (ILK) is an important modulator of actin cytoskeletal dynamics. We have examined the role of ILK in regulation of phagocytosis, using epidermal keratinocytes isolated from mice with epidermis-restricted Ilk gene inactivation. ILK-deficient cells exhibited severely impaired capacity to engulf fluorescent microspheres in response to stimulation of the keratinocyte growth factor (KGF) receptor or the protease-activated receptor-2. KGF induced ERK phosphorylation in ILK-expressing and ILK-deficient cells, suggesting that ILK is not essential for KGF receptor signaling. In contrast, KGF promoted activation of Rac1 and formation of pseudopodia in ILK-expressing, but not in ILK-deficient cells. Rac1-deficient keratinocytes also showed substantially impaired phagocytic ability, underlining the importance of ILK-dependent Rac1 function for particle engulfment. Finally, cross-modulation of KGF receptors by integrins may be another important element, as integrin β1-deficient keratinocytes also fail to show significant phagocytosis in response to KGF. Thus, we have identified a novel signaling pathway essential for phagocytosis in keratinocytes, which involves ILK-dependent activation of Rac1 in response to KGF, resulting in the formation of pseudopodia and particle uptake.

Pseudomonas aeruginosa essentials: an update on investigation of essential genes.

PubMed

Juhas, Mario

2015-11-01

Pseudomonas aeruginosa is the leading cause of nosocomial infections, particularly in immunocompromised, cancer, burn and cystic fibrosis patients. Development of novel antimicrobials against P. aeruginosa is therefore of the highest importance. Although the first reports on P. aeruginosa essential genes date back to the early 2000s, a number of more sensitive genomic approaches have been used recently to better define essential genes in this organism. These analyses highlight the evolution of the definition of an 'essential' gene from the traditional to the context-dependent. Essential genes, particularly those indispensable under the clinically relevant conditions, are considered to be promising targets of novel antibiotics against P. aeruginosa. This review provides an update on the investigation of P. aeruginosa essential genes. Special focus is on recently identified P. aeruginosa essential genes and their exploitation for the development of antimicrobials.

Open-Source Software for Modeling of Nanoelectronic Devices

NASA Technical Reports Server (NTRS)

Oyafuso, Fabiano; Hua, Hook; Tisdale, Edwin; Hart, Don

2004-01-01

The Nanoelectronic Modeling 3-D (NEMO 3-D) computer program has been upgraded to open-source status through elimination of license-restricted components. The present version functions equivalently to the version reported in "Software for Numerical Modeling of Nanoelectronic Devices" (NPO-30520), NASA Tech Briefs, Vol. 27, No. 11 (November 2003), page 37. To recapitulate: NEMO 3-D performs numerical modeling of the electronic transport and structural properties of a semiconductor device that has overall dimensions of the order of tens of nanometers. The underlying mathematical model represents the quantum-mechanical behavior of the device resolved to the atomistic level of granularity. NEMO 3-D solves the applicable quantum matrix equation on a Beowulf-class cluster computer by use of a parallel-processing matrix vector multiplication algorithm coupled to a Lanczos and/or Rayleigh-Ritz algorithm that solves for eigenvalues. A prior upgrade of NEMO 3-D incorporated a capability for a strain treatment, parameterized for bulk material properties of GaAs and InAs, for two tight-binding submodels. NEMO 3-D has been demonstrated in atomistic analyses of effects of disorder in alloys and, in particular, in bulk In(x)Ga(1-x)As and in In(0.6)Ga(0.4)As quantum dots.

Essential tremor

MedlinePlus

... Tremor - familial; Benign essential tremor; Shaking - essential tremor Images Central nervous system and peripheral nervous system References Jankovic J. Parkinson disease and other movement disorders. In: Daroff ...

Enhancement of the Norfloxacin Antibiotic Activity by Gaseous Contact with the Essential Oil of Croton zehntneri

PubMed Central

Coutinho, HDM; Matias, EFF; Santos, KKA; Tintino, SR; Souza, CES; Guedes, GMM; Santos, FAD; Costa, JGM; Falcão-Silva, VS; Siqueira-Júnior, JP

2010-01-01

This is the first on the modulation of norfloxacin antibiotic activity by the volatile compounds of an essential oil. We report the chemical composition and antibiotic modifying activity of the essential oil extracted from the leaves of Croton zehntneri Pax et Hoffm (variety estragole), using the minimal inhibitory dose method and gaseous contact. The leaves of Croton zehntneri Pax et Hoffm (Euphorbiaceae) were subjected to hydrodistillation, and the essential oil extracted was examined with respect to the chemical composition, by gas chromatography-mass spectrometry (GC/MS), and to inhibitory activity of efflux pump by gaseous contact. The main component of the essential oil of C. zehntneri was estragole (76,8%). The gaseous components of the oil enhanced the inhibition zone of norfloxacin in 39,5%. This result shows that this oil influences the antibiotic activity of norfloxacin, possibly affecting the bacterial NorA efflux system, and may be used as an adjuvant in the antibiotic therapy of multidrug resistant pathogens. PMID:21264094

A Drosophila Model of Essential Tremor.

PubMed

Smith, Philip; Arias, Ronald; Sonti, Shilpa; Odgerel, Zagaa; Santa-Maria, Ismael; McCabe, Brian D; Tsaneva-Atanasova, Krasimira; Louis, Elan D; Hodge, James J L; Clark, Lorraine N

2018-05-16

Essential Tremor (ET) is one of the most common neurological diseases, with an estimated 7 million affected individuals in the US; the pathophysiology of the disorder is poorly understood. Recently, we identified a mutation (KCNS2 (Kv9.2), c.1137 T > A, p.(D379E) in an electrically silent voltage-gated K + channel α-subunit, Kv9.2, in a family with ET, that modulates the activity of Kv2 channels. We have produced transgenic Drosophila lines that express either the human wild type Kv9.2 (hKv9.2) or the ET causing mutant Kv9.2 (hKv9.2-D379E) subunit in all neurons. We show that the hKv9.2 subunit modulates activity of endogenous Drosophila K + channel Shab. The mutant hKv9.2-D379E subunit showed significantly higher levels of Shab inactivation and a higher frequency of spontaneous firing rate consistent with neuronal hyperexcitibility. We also observed behavioral manifestations of nervous system dysfunction including effects on night time activity and sleep. This functional data further supports the pathogenicity of the KCNS2 (p.D379E) mutation, consistent with our prior observations including co-segregation with ET in a family, a likely pathogenic change in the channel pore domain and absence from population databases. The Drosophila hKv9.2 transgenic model recapitulates several features of ET and may be employed to advance our understanding of ET disease pathogenesis.

Kinetic Behavior of Leucine and Other Amino Acids Modulating Cognitive Performance via mTOR Pathway

DTIC Science & Technology

2011-12-02

is a potential target for modulation with leucine (or other therapeutic agents), to maintain/enhance normal functioning under stress conditions. Such... functioning under stress conditions. Such an effect has potential for optimizing warfighter cognitive performance under high demand conditions. The... Isoleucine L1 Essential Neutral Non-polar Branched chain Lysine Basic Y+ Essential Basic Polar Proline L1? Neutral Non-polar Aromatic Asparagine Neutral

Anti-oxidative and anti-inflammatory effects of Tagetes minuta essential oil in activated macrophages

PubMed Central

Karimian, Parastoo; Kavoosi, Gholamreza; Amirghofran, Zahra

2014-01-01

Objective To investigate antioxidant and anti-inflammatory effects of Tagetes minuta (T. minuta) essential oil. Methods In the present study T. minuta essential oil was obtained from leaves of T. minuta via hydro-distillation and then was analyzed by gas chromatography-mass spectrometry. The anti-oxidant capacity of T. minuta essential oil was examined by measuring reactive oxygen, reactive nitrogen species and hydrogen peroxide scavenging. The anti-inflammatory activity of T. minuta essential oil was determined through measuring NADH oxidase, inducible nitric oxide synthase and TNF-α mRNA expression in lipopolysacharide-stimulated murine macrophages using real-time PCR. Results Gas chromatography-mass spectrometry analysis indicated that the main components in the T. minuta essential oil were dihydrotagetone (33.86%), E-ocimene (19.92%), tagetone (16.15%), cis-β-ocimene (7.94%), Z-ocimene (5.27%), limonene (3.1%) and epoxyocimene (2.03%). The T. minuta essential oil had the ability to scavenge all reactive oxygen/reactive nitrogen species radicals with IC50 12-15 µg/mL, which indicated a potent radical scavenging activity. In addition, T. minuta essential oil significantly reduced NADH oxidase, inducible nitric oxide synthaseand TNF-α mRNA expression in the cells at concentrations of 50 µg/mL, indicating a capacity of this product to potentially modulate/diminish immune responses. Conclusions T. minuta essential oil has radical scavenging and anti-inflammatory activities and could potentially be used as a safe effective source of natural anti-oxidants in therapy against oxidative damage and stress associated with some inflammatory conditions. PMID:25182441

Attenuation of microglial RANTES by NEMO-binding domain peptide inhibits the infiltration of CD8(+) T cells in the nigra of hemiparkinsonian monkey.

PubMed

Roy, A; Mondal, S; Kordower, J H; Pahan, K

2015-08-27

Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). Despite intense investigations, little is known about its pathological mediators. Here, we report the marked upregulation of RANTES (regulated on activation, normal T cell expressed and secreted) and eotaxin, chemokines that are involved in T cell trafficking, in the serum of hemiparkinsonian monkeys. Interestingly, 1-methyl-4-phenylpyridinium (MPP(+)), a Parkinsonian toxin, increased the expression of RANTES and eotaxin in mouse microglial cells. The presence of NF-κB binding sites in promoters of RANTES and eotaxin and down-regulation of these genes by NEMO-binding domain (NBD) peptide, selective inhibitor of induced NF-κB activation, in MPP(+)-stimulated microglial cells suggest that the activation of NF-κB plays an important role in the upregulation of these two chemokines. Consistently, serum enzyme-linked immuno assay (ELISA) and nigral immunohistochemistry further confirmed that these chemokines were strongly upregulated in MPTP-induced hemiparkinsonian monkeys and that treatment with NBD peptides effectively inhibited the level of these chemokines. Furthermore, the microglial upregulation of RANTES in the nigra of hemiparkinsonian monkeys could be involved in the altered adaptive immune response in the brain as we observed greater infiltration of CD8(+) T cells around the perivascular niche and deep brain parenchyma of hemiparkinsonian monkeys as compared to control. The treatment of hemiparkinsonian monkeys with NBD peptides decreased the microglial expression of RANTES and attenuated the infiltration of CD8(+) T cells in nigra. These results indicate the possible involvement of chemokine-dependent adaptive immune response in Parkinsonism. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

A heteromeric potassium channel involved in the modulation of the plasma membrane potential is essential for the survival of African trypanosomes.

PubMed

Steinmann, Michael E; González-Salgado, Amaia; Bütikofer, Peter; Mäser, Pascal; Sigel, Erwin

2015-08-01

Discovery of novel drug targets may lead to improved treatment of trypanosomiasis. We characterize here 2 gene products of Trypanosoma brucei that are essential for the growth of bloodstream form (BSF) parasites, as shown by RNA interference (RNAi)-mediated down-regulation of the individual mRNAs. The primary sequences of the 2 proteins--protein encoded by gene Tb927.1.4450 (TbK1) and protein encoded by gene Tb927.9.4820 (TbK2)--indicate that both belong to the family of putative, Ca(2+)-activated potassium channels. The proteins were expressed in Xenopus laevis oocytes and their functions investigated by use of electrophysiological techniques. Only combined expression of TbK1 and TbK2 results in the formation of sizeable currents, indicating that these proteins probably assemble into a heteromeric ion channel. The current mediated by this channel shows little time and voltage dependence and displays a permeability ratio of K(+)/Na(+) of >20. The known potassium channel blocker barium inhibits this channel with a half-maximal inhibitory concentration (IC50) of 98 ± 15 μM. The membrane potential of trypanosomes was measured with a fluorescent dye. Individual RNAi-mediated down-regulation of TbK1 or TbK2 eliminates a potassium conductance in the plasma membrane of BSF. Thus, this heteromeric potassium channel is involved in the modulation of the plasma membrane potential and represents a novel drug target in T. brucei. © FASEB.

Tax-Independent Constitutive IκB Kinase Activation in Adult T-Cell Leukemia Cells1

PubMed Central

Hironaka, Noriko; Mochida, Kanako; Mori, Naoki; Maeda, Michiyuki; Yamamoto, Naoki; Yamaoka, Shoji

2004-01-01

Abstract Adult T-cell leukemia (ATL) is a fatal T-cell malignancy that arises long after infection with human T-cell leukemia virus type I (HTLV-I). We reported previously that nuclear factor-κB (NF-κB) was constitutively activated in ATL cells, although expression of the viral proteins was barely detectable, including Tax, which was known to persistently activate NF-κB. Here we demonstrate that ATL cells that do not express detectable Tax protein exhibit constitutive IκB kinase (IKK) activity. Transfection studies revealed that a dominant-negative form of IKK1, and not of IKK2 or NF-κB essential modulator (NEMO), suppressed constitutive NFκB activity in ATL cells. This IKK activity was accompanied by elevated expression of p52, suggesting that the recently described noncanonical pathway of NF-κB activation operates in ATL cells. We finally show that specific inhibition of NF-κB by a super-repressor form of IκBα (SR-IκBα) in HTLV-I-infected T cells results in cell death regardless of Tax expression, providing definitive evidence of an essential role for NF-κB in the survival of ATL cells. In conclusion, the IKK complex is constitutively activated in ATL cells through a cellular mechanism distinct from that of Tax-mediated IKK activation. Further elucidation of this cellular mechanism should contribute to establishing a rationale for treatment of ATL. PMID:15153339

Essential Characteristics for a Professional Development Program for Promoting the Implementation of a Multidisciplinary Science Module

ERIC Educational Resources Information Center

Visser, Talitha C.; Coenders, Fer G. M.; Terlouw, Cees; Pieters, Jules M.

2010-01-01

Teachers involved in the implementation of a curriculum innovation can be prepared for this task through a professional development program. In this paper, we describe essential characteristics (identified empirically and theoretically) for such a professional development program that promotes the acquisition of competences by these teachers. The…

Advanced energy systems and technologies - National R and D programme

NASA Astrophysics Data System (ADS)

Lund, P. D.

1992-08-01

The energy R and D in Finland is accomplished through the energy research programs of the Ministry of Trade and Industry. Today there are some 12 R and D programs in operation covering the various aspects of the energy sector. The NEMO-program deals with advanced new energy technologies and systems. The NEMO-program was launched in 1988 and it ends at the end of 1992. Helsinki University of Technology has been responsible for the coordination and most of the universities, research centers, and companies on new advanced energy technologies have been involved in the realization of NEMO. The objectives of the program have been to assess the potential of new technologies in the Finnish energy supply system, encourage and support businesses, and to create necessary research tradition in Finland. At the beginning in year 1988, several new technologies were included, but as the knowledge has increased, focusing on the most promising fields has taken place. Wind and solar energy show the best promises in respect to business activities and possibilities for utilization in Finland. Energy storage some other advanced technologies such as fuel cells and hydrogen technologies represented in the NEMO-program have an important role, but the commercial applications lie more distant in the future. The NEMO-program has reached its objectives. The international evaluation in fall 1990 gave very positive feedback and the scientific quality of the work was found good. At the same time, the contents was still focused more on commercial applications to support national industries in the field. The descriptions of the ongoing NEMO research projects are included in this report.

TACE/ADAM17 is essential for oligodendrocyte development and CNS myelination.

PubMed

Palazuelos, Javier; Crawford, Howard C; Klingener, Michael; Sun, Bingru; Karelis, Jason; Raines, Elaine W; Aguirre, Adan

2014-09-03

Several studies have elucidated the significance of a disintegrin and metalloproteinase proteins (ADAMs) in PNS myelination, but there is no evidence if they also play a role in oligodendrogenesis and CNS myelination. Our study identifies ADAM17, also called tumor necrosis factor-α converting enzyme (TACE), as a novel key modulator of oligodendrocyte (OL) development and CNS myelination. Genetic deletion of TACE in oligodendrocyte progenitor cells (OPs) induces premature cell cycle exit and reduces OL cell survival during postnatal myelination of the subcortical white matter (SCWM). These cellular and molecular changes lead to deficits in SCWM myelination and motor behavior. Mechanistically, TACE regulates oligodendrogenesis by modulating the shedding of EGFR ligands TGFα and HB-EGF and, consequently, EGFR signaling activation in OL lineage cells. Constitutive TACE depletion in OPs in vivo leads to similar alterations in CNS myelination and motor behavior as to what is observed in the EGFR hypofunctional mouse line EgfrWa2. EGFR overexpression in TACE-deficient OPs restores OL survival and development. Our study reveals an essential function of TACE in oligodendrogenesis, and demonstrates how this molecule modulates EGFR signaling activation to regulate postnatal CNS myelination. Copyright © 2014 the authors 0270-6474/14/3411884-13$15.00/0.

Spectroscopic Studies of Double Beta Decays and MOON

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

Ejiri, H.; Nuclear Science, Czech Technical University, Brehova, Prague, Czech Republic, National Institute of Radiological Sciences, Chiba, 263-8555

2007-10-12

This is a brief review of future spectroscopic experiments of neutrino-less double beta decays (0{nu}{beta}{beta}) and the MOON (Mo Observatory Of Neutrinos) project. Spectroscopic 0{nu}{beta}{beta} experiments of MOON, SuperNEMO and DCBA are planned to study Majorana masses in the quasi-degenerate (QD) and inverted mass hierarchy (IH) regions. MOON aims at 0{nu}{beta}{beta} studies with the {nu}-mass sensitivities of 100-30 meV by means of a super ensemble of multi-layer modules, each being consist of a scintillator plate, two tracking detector planes and a thin {beta}{beta} source film.

Antioxidant activity of rosemary (Rosmarinus officinalis L.) essential oil and its hepatoprotective potential

PubMed Central

2014-01-01

Background Natural antioxidant products are increasingly being used to treat various pathological liver conditions considering the role of oxidative stress in their pathogenesis. Rosemary essential oil has already being used as a preservative in food industry due to its antioxidant and antimicrobial activities, but it was shown to possess additional health benefits. The aim of our study was to evaluate the protective effect of rosemary essential oil on carbon tetrachloride - induced liver injury in rats and to explore whether its mechanism of action is associated with modulation of hepatic oxidative status. Methods Chemical composition of isolated rosemary essential oil was determined by gas chromatography and mass spectrometry. Antioxidant activity was determined in vitro using DPPH assay. Activities of enzyme markers of hepatocellular damage in serum and antioxidant enzymes in the liver homogenates were measured using the kinetic spectrophotometric methods. Results In this research, we identified 29 chemical compounds of the studied rosemary essential oil, and the main constituents were 1,8-cineole (43.77%), camphor (12.53%), and α-pinene (11.51%). Investigated essential oil was found to exert hepatoprotective effects in the doses of 5 mg/kg and 10 mg/kg by diminishing AST and ALT activities up to 2-fold in serum of rats with carbon tetrachloride - induced acute liver damage. Rosemary essential oil prevented carbon tetrachloride - induced increase of lipid peroxidation in liver homogenates. Furthermore, pre-treatment with studied essential oil during 7 days significantly reversed the activities of antioxidant enzymes catalase, peroxidase, glutathione peroxidase and glutathione reductase in liver homogenates, especially in the dose of 10 mg/kg. Conclusions Our results demonstrate that rosemary essential oil, beside exhibiting free radical scavenging activity determined by DPPH assay, mediates its hepatoprotective effects also through activation of

Antioxidant activity of rosemary (Rosmarinus officinalis L.) essential oil and its hepatoprotective potential.

PubMed

Rašković, Aleksandar; Milanović, Isidora; Pavlović, Nebojša; Ćebović, Tatjana; Vukmirović, Saša; Mikov, Momir

2014-07-07

Natural antioxidant products are increasingly being used to treat various pathological liver conditions considering the role of oxidative stress in their pathogenesis. Rosemary essential oil has already being used as a preservative in food industry due to its antioxidant and antimicrobial activities, but it was shown to possess additional health benefits. The aim of our study was to evaluate the protective effect of rosemary essential oil on carbon tetrachloride - induced liver injury in rats and to explore whether its mechanism of action is associated with modulation of hepatic oxidative status. Chemical composition of isolated rosemary essential oil was determined by gas chromatography and mass spectrometry. Antioxidant activity was determined in vitro using DPPH assay. Activities of enzyme markers of hepatocellular damage in serum and antioxidant enzymes in the liver homogenates were measured using the kinetic spectrophotometric methods. In this research, we identified 29 chemical compounds of the studied rosemary essential oil, and the main constituents were 1,8-cineole (43.77%), camphor (12.53%), and α-pinene (11.51%). Investigated essential oil was found to exert hepatoprotective effects in the doses of 5 mg/kg and 10 mg/kg by diminishing AST and ALT activities up to 2-fold in serum of rats with carbon tetrachloride-induced acute liver damage. Rosemary essential oil prevented carbon tetrachloride-induced increase of lipid peroxidation in liver homogenates. Furthermore, pre-treatment with studied essential oil during 7 days significantly reversed the activities of antioxidant enzymes catalase, peroxidase, glutathione peroxidase and glutathione reductase in liver homogenates, especially in the dose of 10 mg/kg. Our results demonstrate that rosemary essential oil, beside exhibiting free radical scavenging activity determined by DPPH assay, mediates its hepatoprotective effects also through activation of physiological defense mechanisms.

Temporal characteristic analysis of laser-modulated pulsed X-ray source for space X-ray communication

NASA Astrophysics Data System (ADS)

Hang, Shuang; Liu, Yunpeng; Li, Huan; Tang, Xiaobin; Chen, Da

2018-04-01

X-ray communication (XCOM) is a new communication type and is expected to realize high-speed data transmission in some special communication scenarios, such as deep space communication and blackout communication. This study proposes a high-speed modulated X-ray source scheme based on the laser-to-X-ray conversion. The temporal characteristics of the essential components of the proposed laser-modulated pulsed X-ray source (LMPXS) were analyzed to evaluate its pulse emission performance. Results show that the LMPXS can provide a maximum modulation rate up to 100 Mbps which is expected to significantly improve the data rate of XCOM.

Rapid Mars transits with exhaust-modulated plasma propulsion

NASA Technical Reports Server (NTRS)

Chang-Diaz, Franklin R.; Braden, Ellen; Johnson, Ivan; Hsu, Michael M.; Yang, Tien Fang

1995-01-01

The operational characteristics of the Exhaust-Modulated Plasma Rocket are described. Four basic human and robotic mission scenarios to Mars are analyzed using numerical optimization techniques at variable specific impulse and constant power. The device is well suited for 'split-sprint' missions, allowing fast, one-way low-payload human transits of 90 to 104 days, as well as slower, 180-day, high-payload robotic precursor flights. Abort capabilities, essential for human missions, are also explored.

O-GlcNAcylation is a key modulator of skeletal muscle sarcomeric morphometry associated to modulation of protein-protein interactions.

PubMed

Lambert, Matthias; Richard, Elodie; Duban-Deweer, Sophie; Krzewinski, Frederic; Deracinois, Barbara; Dupont, Erwan; Bastide, Bruno; Cieniewski-Bernard, Caroline

2016-09-01

The sarcomere structure of skeletal muscle is determined through multiple protein-protein interactions within an intricate sarcomeric cytoskeleton network. The molecular mechanisms involved in the regulation of this sarcomeric organization, essential to muscle function, remain unclear. O-GlcNAcylation, a post-translational modification modifying several key structural proteins and previously described as a modulator of the contractile activity, was never considered to date in the sarcomeric organization. C2C12 skeletal myotubes were treated with Thiamet-G (OGA inhibitor) in order to increase the global O-GlcNAcylation level. Our data clearly showed a modulation of the O-GlcNAc level more sensitive and dynamic in the myofilament-enriched fraction than total proteome. This fine O-GlcNAc level modulation was closely related to changes of the sarcomeric morphometry. Indeed, the dark-band and M-line widths increased, while the I-band width and the sarcomere length decreased according to the myofilament O-GlcNAc level. Some structural proteins of the sarcomere such as desmin, αB-crystallin, α-actinin, moesin and filamin-C have been identified within modulated protein complexes through O-GlcNAc level variations. Their interactions seemed to be changed, especially for desmin and αB-crystallin. For the first time, our findings clearly demonstrate that O-GlcNAcylation, through dynamic regulations of the structural interactome, could be an important modulator of the sarcomeric structure and may provide new insights in the understanding of molecular mechanisms of neuromuscular diseases characterized by a disorganization of the sarcomeric structure. In the present study, we demonstrated a role of O-GlcNAcylation in the sarcomeric structure modulation. Copyright © 2016 Elsevier B.V. All rights reserved.

A Near-Infrared Spectrometer Based on Novel Grating Light Modulators

PubMed Central

Wei, Wei; Huang, Shanglian; Wang, Ning; Jin, Zhu; Zhang, Jie; Chen, Weimin

2009-01-01

A near-infrared spectrometer based on novel MOEMS grating light modulators is proposed. The spectrum detection method that combines a grating light modulator array with a single near-infrared detector has been applied. Firstly, optics theory has been used to analyze the essential principles of the proposed spectroscopic sensor. Secondly, the grating light modulators have been designed and fabricated by micro-machining technology. Finally, the principles of this spectroscopic sensor have been validated and its key parameters have been tested by experiments. The result shows that the spectral resolution is better than 10 nm, the wavelength deviation is less than 1 nm, the deviation of the intensity of peak wavelength is no more than 0.5%, the driving voltage of grating light modulators array device is below 25 V and the response frequency of it is about 5 kHz. With low cost, satisfactory precision, portability and other advantages, the spectrometer should find potential applications in food safety and quality monitoring, pharmaceutical identification and agriculture product quality classification. PMID:22574065

A near-infrared spectrometer based on novel grating light modulators.

PubMed

Wei, Wei; Huang, Shanglian; Wang, Ning; Jin, Zhu; Zhang, Jie; Chen, Weimin

2009-01-01

A near-infrared spectrometer based on novel MOEMS grating light modulators is proposed. The spectrum detection method that combines a grating light modulator array with a single near-infrared detector has been applied. Firstly, optics theory has been used to analyze the essential principles of the proposed spectroscopic sensor. Secondly, the grating light modulators have been designed and fabricated by micro-machining technology. Finally, the principles of this spectroscopic sensor have been validated and its key parameters have been tested by experiments. The result shows that the spectral resolution is better than 10 nm, the wavelength deviation is less than 1 nm, the deviation of the intensity of peak wavelength is no more than 0.5%, the driving voltage of grating light modulators array device is below 25 V and the response frequency of it is about 5 kHz. With low cost, satisfactory precision, portability and other advantages, the spectrometer should find potential applications in food safety and quality monitoring, pharmaceutical identification and agriculture product quality classification.

Modulators of 14-3-3 Protein–Protein Interactions

PubMed Central

2017-01-01

Direct interactions between proteins are essential for the regulation of their functions in biological pathways. Targeting the complex network of protein–protein interactions (PPIs) has now been widely recognized as an attractive means to therapeutically intervene in disease states. Even though this is a challenging endeavor and PPIs have long been regarded as “undruggable” targets, the last two decades have seen an increasing number of successful examples of PPI modulators, resulting in growing interest in this field. PPI modulation requires novel approaches and the integrated efforts of multiple disciplines to be a fruitful strategy. This perspective focuses on the hub-protein 14-3-3, which has several hundred identified protein interaction partners, and is therefore involved in a wide range of cellular processes and diseases. Here, we aim to provide an integrated overview of the approaches explored for the modulation of 14-3-3 PPIs and review the examples resulting from these efforts in both inhibiting and stabilizing specific 14-3-3 protein complexes by small molecules, peptide mimetics, and natural products. PMID:28968506

Identification of Genes Controlled by the Essential YycFG Two-Component System Reveals a Role for Biofilm Modulation in Staphylococcus epidermidis.

PubMed

Xu, Tao; Wu, Yang; Lin, Zhiwei; Bertram, Ralph; Götz, Friedrich; Zhang, Ying; Qu, Di

2017-01-01

Biofilms play a crucial role in the pathogenicity of Staphylococcus epidermidis , while little is known about whether the essential YycFG two-component signal transduction system (TCS) is involved in biofilm formation. We used antisense RNA (asRNA) to silence the yycFG TCS in order to study its regulatory functions in S. epidermidis . Strain 1457 expressing asRNA yycF exhibited a significant delay (~4-5 h) in entry to log phase, which was partially complemented by overexpressing ssaA . The expression of asRNA yycF and asRNA yycG resulted in a 68 and 50% decrease in biofilm formation at 6 h, respectively, while they had no significant inhibitory effect on 12 h biofilm formation. The expression of asRNA yycF led to a ~5-fold increase in polysaccharide intercellular adhesion (PIA) production, but it did not affect the expression of accumulation-associated protein (Aap) or the release of extracellular DNA. Consistently, quantitative real-time PCR showed that silencing yycF resulted in an increased transcription of biofilm-related genes, including icaA, arlR, sarA, sarX , and sbp . An in silico search of the YycF regulon for the conserved YycF recognition pattern and a modified motif in S. epidermidis , along with additional gel shift and DNase I footprinting assays, showed that arlR, sarA, sarX , and icaA are directly regulated by YycF. Our data suggests that YycFG modulates S. epidermidis biofilm formation in an ica-dependent manner.

Identification of Genes Controlled by the Essential YycFG Two-Component System Reveals a Role for Biofilm Modulation in Staphylococcus epidermidis

PubMed Central

Xu, Tao; Wu, Yang; Lin, Zhiwei; Bertram, Ralph; Götz, Friedrich; Zhang, Ying; Qu, Di

2017-01-01

Biofilms play a crucial role in the pathogenicity of Staphylococcus epidermidis, while little is known about whether the essential YycFG two-component signal transduction system (TCS) is involved in biofilm formation. We used antisense RNA (asRNA) to silence the yycFG TCS in order to study its regulatory functions in S. epidermidis. Strain 1457 expressing asRNAyycF exhibited a significant delay (~4–5 h) in entry to log phase, which was partially complemented by overexpressing ssaA. The expression of asRNAyycF and asRNAyycG resulted in a 68 and 50% decrease in biofilm formation at 6 h, respectively, while they had no significant inhibitory effect on 12 h biofilm formation. The expression of asRNAyycF led to a ~5-fold increase in polysaccharide intercellular adhesion (PIA) production, but it did not affect the expression of accumulation-associated protein (Aap) or the release of extracellular DNA. Consistently, quantitative real-time PCR showed that silencing yycF resulted in an increased transcription of biofilm-related genes, including icaA, arlR, sarA, sarX, and sbp. An in silico search of the YycF regulon for the conserved YycF recognition pattern and a modified motif in S. epidermidis, along with additional gel shift and DNase I footprinting assays, showed that arlR, sarA, sarX, and icaA are directly regulated by YycF. Our data suggests that YycFG modulates S. epidermidis biofilm formation in an ica-dependent manner. PMID:28491057

Resonant Tunneling Quantum Well Integrated Optical Waveguide Modulator/ Switch

DTIC Science & Technology

1994-07-01

time, which leads to the high speed operation. In this Phase I project, POC designed the RTDBQW device, including the optimization and precise definition...Effect of Free Carriers ............ 7 3.0 CHANNEL WAVEGUIDE DESIGN AND OPTIMIZATION ................... 10 3.1 Design Of Directional Coupling Mach...are essential for high speed signal routing and regeneration. POC’s design relies on the integration of an optical guided wave switch/modulator with a

Identification of common coexpression modules based on quantitative network comparison.

PubMed

Jo, Yousang; Kim, Sanghyeon; Lee, Doheon

2018-06-13

Finding common molecular interactions from different samples is essential work to understanding diseases and other biological processes. Coexpression networks and their modules directly reflect sample-specific interactions among genes. Therefore, identification of common coexpression network or modules may reveal the molecular mechanism of complex disease or the relationship between biological processes. However, there has been no quantitative network comparison method for coexpression networks and we examined previous methods for other networks that cannot be applied to coexpression network. Therefore, we aimed to propose quantitative comparison methods for coexpression networks and to find common biological mechanisms between Huntington's disease and brain aging by the new method. We proposed two similarity measures for quantitative comparison of coexpression networks. Then, we performed experiments using known coexpression networks. We showed the validity of two measures and evaluated threshold values for similar coexpression network pairs from experiments. Using these similarity measures and thresholds, we quantitatively measured the similarity between disease-specific and aging-related coexpression modules and found similar Huntington's disease-aging coexpression module pairs. We identified similar Huntington's disease-aging coexpression module pairs and found that these modules are related to brain development, cell death, and immune response. It suggests that up-regulated cell signalling related cell death and immune/ inflammation response may be the common molecular mechanisms in the pathophysiology of HD and normal brain aging in the frontal cortex.

Functional Interaction between Phosducin-like Protein 2 and Cytosolic Chaperonin Is Essential for Cytoskeletal Protein Function and Cell Cycle Progression

PubMed Central

Stirling, Peter C.; Srayko, Martin; Takhar, Karam S.; Pozniakovsky, Andrei; Hyman, Anthony A.

2007-01-01

The C haperonin Containing Tcp1 (CCT) maintains cellular protein folding homeostasis in the eukaryotic cytosol by assisting the biogenesis of many proteins, including actins, tubulins, and regulators of the cell cycle. Here, we demonstrate that the essential and conserved eukaryotic phosducin-like protein 2 (PhLP2/PLP2) physically interacts with CCT and modulates its folding activity. Consistent with this functional interaction, temperature-sensitive alleles of Saccharomyces cerevisiae PLP2 exhibit cytoskeletal and cell cycle defects. We uncovered several high-copy suppressors of the plp2 alleles, all of which are associated with G1/S cell cycle progression but which do not appreciably affect cytoskeletal protein function or fully rescue the growth defects. Our data support a model in which Plp2p modulates the biogenesis of several CCT substrates relating to cell cycle and cytoskeletal function, which together contribute to the essential function of PLP2. PMID:17429077

Essential Oils from the Medicinal Herbs Upregulate Dopamine Transporter in Rat Pheochromocytoma Cells.

PubMed

Choi, Min Sun; Choi, Bang-sub; Kim, Sang Heon; Pak, Sok Cheon; Jang, Chul Ho; Chin, Young-Won; Kim, Young-Mi; Kim, Dong-il; Jeon, Songhee; Koo, Byung-Soo

2015-10-01

The dopamine transporter (DAT) protein, a component of the dopamine system, undergoes adaptive neurobiological changes from drug abuse. Prevention of relapse and reduction of withdrawal symptoms are still the major limitations in the current pharmacological treatments of drug addiction. The present study aimed to investigate the effects of essential oils extracted from Elsholtzia ciliata, Shinchim, Angelicae gigantis Radix, and Eugenia caryophyllata, well-known traditional Korean medicines for addiction, on the modulation of dopamine system in amphetamine-treated cells and to explore the possible mechanism underlying its therapeutic effect. The potential cytotoxic effect of essential oils was evaluated in PC12 rat pheochromocytoma cells using cell viability assays. Quantification of DAT, p-CREB, p-MAPK, and p-Akt was done by immunoblotting. DAT was significantly reduced in cells treated with 50 μM of amphetamine in a time-dependent manner. No significant toxicity of essential oils from Elsholtzia ciliata and Shinchim was observed at doses of 10, 25, and 50 μg/mL. However, essential oils from A. gigantis Radix at a dose of 100 μg/mL and E. caryophyllata at doses of 50 and 100 μg/mL showed cytotoxicity. Treatment with GBR 12909, a highly selective DAT inhibitor, significantly increased DAT expression compared with that of amphetamine only by enhancing phosphorylation of mitogen-activated protein kinases (MAPK) and Akt. In addition, essential oils effectively induced hyperphosphorylation of cyclic-AMP response element-binding protein (CREB), MAPK, and Akt, which resulted in DAT upregulation. Our study implies that the essential oils may rehabilitate brain dopamine function through increased DAT availability in abstinent former drug users.

Vaporizable Scaffolds for Fabricating Thermoelectric Modules

NASA Technical Reports Server (NTRS)

Sakamoto, Jeffrey; Yen, Shiao-pin; Fleurial, Jean-Pierre; Paik, Jong-Ah

2006-01-01

A process for fabricating thermoelectric modules with vacuum gaps separating the thermoelectric legs has been conceived, and the feasibility of some essential parts of the process has been demonstrated. The vacuum gaps are needed to electrically insulate the legs from each other. The process involves the use of scaffolding in the form of sheets of a polymer to temporarily separate the legs by the desired distance, which is typically about 0.5 mm. During a bonding subprocess that would take place in a partial vacuum at an elevated temperature, the polymer would be vaporized, thereby creating the vacuum gaps.

The behaviour of basic autocatalytic signalling modules in isolation and embedded in networks

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

Krishnan, J.; Mois, Kristina; Suwanmajo, Thapanar

2014-11-07

In this paper, we examine the behaviour of basic autocatalytic feedback modules involving a species catalyzing its own production, either directly or indirectly. We first perform a systematic study of the autocatalytic feedback module in isolation, examining the effect of different factors, showing how this module is capable of exhibiting monostable threshold and bistable switch-like behaviour. We then study the behaviour of this module embedded in different kinds of basic networks including (essentially) irreversible cycles, open and closed reversible chains, and networks with additional feedback. We study the behaviour of the networks deterministically and also stochastically, using simulations, analytical work,more » and bifurcation analysis. We find that (i) there are significant differences between the behaviour of this module in isolation and in a network: thresholds may be altered or destroyed and bistability may be destroyed or even induced, even when the ambient network is simple. The global characteristics and topology of this network and the position of the module in the ambient network can play important and unexpected roles. (ii) There can be important differences between the deterministic and stochastic dynamics of the module embedded in networks, which may be accentuated by the ambient network. This provides new insights into the functioning of such enzymatic modules individually and as part of networks, with relevance to other enzymatic signalling modules as well.« less

The behaviour of basic autocatalytic signalling modules in isolation and embedded in networks

NASA Astrophysics Data System (ADS)

Krishnan, J.; Mois, Kristina; Suwanmajo, Thapanar

2014-11-01

In this paper, we examine the behaviour of basic autocatalytic feedback modules involving a species catalyzing its own production, either directly or indirectly. We first perform a systematic study of the autocatalytic feedback module in isolation, examining the effect of different factors, showing how this module is capable of exhibiting monostable threshold and bistable switch-like behaviour. We then study the behaviour of this module embedded in different kinds of basic networks including (essentially) irreversible cycles, open and closed reversible chains, and networks with additional feedback. We study the behaviour of the networks deterministically and also stochastically, using simulations, analytical work, and bifurcation analysis. We find that (i) there are significant differences between the behaviour of this module in isolation and in a network: thresholds may be altered or destroyed and bistability may be destroyed or even induced, even when the ambient network is simple. The global characteristics and topology of this network and the position of the module in the ambient network can play important and unexpected roles. (ii) There can be important differences between the deterministic and stochastic dynamics of the module embedded in networks, which may be accentuated by the ambient network. This provides new insights into the functioning of such enzymatic modules individually and as part of networks, with relevance to other enzymatic signalling modules as well.

The role of adipose-derived inflammatory cytokines in type 1 diabetes

PubMed Central

Shao, Lan; Feng, Boya; Zhang, Yuying; Zhou, Huanjiao; Ji, Weidong; Min, Wang

2016-01-01

ABSTRACT Adipose tissue dysfunction correlates with the development of diabetes. Mice with an adipocyte-specific deletion of the SUMO-specific protease SENP1 develop symptoms of type-1 diabetes mellitus (T1DM). Peri-pancreatic adipocytes (PATs) exert both systemic and paracrine effects on pancreases function. Our recent studies report that PATs of SENP1-deficient mice have increased proinflammatory cytokine production compared with other adipose depots. Proinflammatory cytokines produced from PATs not only have direct cytotoxic effects on pancreatic islets, but also increase CCL5 expression in adjacent pancreatic islets, which induces persistent inflammation in pancreases by acquisition of Th1 and Th17 effector T cell subsets. Small ubiquitin-like modifier (SUMO) can post-translationally conjugate to cellular proteins (SUMOylation) and modulate their biological functions. Several components in SUMOylation associate with T1DM susceptibility. We find that SUMOylation of NF-κB essential molecule NEMO augments NF-κB activity, NF-κB-dependent cytokine production and pancreatic inflammation. NF-κB inhibitor should provide therapeutic approach to block PAT inflammation and ameliorate the T1DM phenotype. We further propose that adipocytes in PATs may play a primary role in establishing pancreatic immune regulation at onset of diabetes, providing new insights into the molecular pathogenesis of type 1 diabetes. PMID:27617172

Composition, anti-quorum sensing and antimicrobial activity of essential oils from Lippia alba.

PubMed

Olivero-Verbel, Jesus; Barreto-Maya, Ana; Bertel-Sevilla, Angela; Stashenko, Elena E

2014-01-01

Many Gram-negative pathogens have the ability to produce N-acylhomoserine lactones (AHLs) as signal molecules for quorum sensing (QS). This cell-cell communication system allows them to coordinate gene expression and regulate virulence. Strategies to inhibit QS are promising for the control of infectious diseases or antibiotic resistant bacterial pathogens. The aim of the present study was to evaluate the anti-quorum sensing (anti-QS) and antibacterial potential of five essential oils isolated from Lippia alba on the Tn-5 mutant of Chromobacterium violaceum CV026, and on the growth of the gram-positive bacteria S. aureus ATCC 25923. The anti-QS activity was detected through the inhibition of the QS-controlled violacein pigment production by the sensor bacteria. Results showed that two essential oils from L. alba, one containing the greatest geranial:neral and the other the highest limonene:carvone concentrations, were the most effective QS inhibitors. Both oils also had small effects on cell growth. Moreover, the geranial/neral chemotype oil also produced the maximum zone of growth inhibition against S. aureus ATCC 25923. These data suggest essential oils from L. alba have promising properties as QS modulators, and present antibacterial activity on S. aureus.

The DAN family: modulators of TGF-β signaling and beyond.

PubMed

Nolan, Kristof; Thompson, Thomas B

2014-08-01

Extracellular binding proteins or antagonists are important factors that modulate ligands in the transforming growth factor (TGF-β) family. While the interplay between antagonists and ligands are essential for developmental and normal cellular processes, their imbalance can lead to the pathology of several disease states. In particular, recent studies have implicated members of the differential screening-selected gene in neuroblastoma (DAN) family in disease such as renal fibrosis, pulmonary arterial hypertension, and reactivation of metastatic cancer stem cells. DAN family members are known to inhibit the bone morphogenetic proteins (BMP) of the TGF-β family. However, unlike other TGF-β antagonist families, DAN family members have roles beyond ligand inhibition and can modulate Wnt and vascular endothelial growth factor (VEGF) signaling pathways. This review describes recent structural and functional advances that have expanded our understanding of DAN family proteins with regards to BMP inhibition and also highlights their emerging roles in the modulation of Wnt and VEGF signaling pathways. © 2014 The Protein Society.

Aerodynamics of the advanced launch system (ALS) propulsion and avionics (P/A) module

NASA Technical Reports Server (NTRS)

Ferguson, Stan; Savage, Dick

1992-01-01

This paper discusses the design and testing of candidate Advanced Launch System (ALS) Propulsion and Avionics (P/A) Module configurations. The P/A Module is a key element of future launch systems because it is essential to the recovery and reuse of high-value propulsion and avionics hardware. The ALS approach involves landing of first stage (booster) and/or second stage (core) P/A modules near the launch site to minimize logistics and refurbishment cost. The key issue addressed herein is the aerodynamic design of the P/A module, including the stability characteristics and the lift-to-drag (L/D) performance required to achieve the necessary landing guidance accuracy. The reference P/A module configuration was found to be statically stable for the desired flight regime, to provide adequate L/D for targeting, and to have effective modulation of the L/D performance using a body flap. The hypersonic aerodynamic trends for nose corner radius, boattail angle and body flap deflections were consistent with pretest predictions. However, the levels for the L/D and axial force for hypersonic Mach numbers were overpredicted by impact theories.

Specific energy yield comparison between crystalline silicon and amorphous silicon based PV modules

NASA Astrophysics Data System (ADS)

Ferenczi, Toby; Stern, Omar; Hartung, Marianne; Mueggenburg, Eike; Lynass, Mark; Bernal, Eva; Mayer, Oliver; Zettl, Marcus

2009-08-01

As emerging thin-film PV technologies continue to penetrate the market and the number of utility scale installations substantially increase, detailed understanding of the performance of the various PV technologies becomes more important. An accurate database for each technology is essential for precise project planning, energy yield prediction and project financing. However recent publications showed that it is very difficult to get accurate and reliable performance data of theses technologies. This paper evaluates previously reported claims the amorphous silicon based PV modules have a higher annual energy yield compared to crystalline silicon modules relative to their rated performance. In order to acquire a detailed understanding of this effect, outdoor module tests were performed at GE Global Research Center in Munich. In this study we examine closely two of the five reported factors that contribute to enhanced energy yield of amorphous silicon modules. We find evidence to support each of these factors and evaluate their relative significance. We discuss aspects for improvement in how PV modules are sold and identify areas for further study further study.

To Modulate and Be Modulated: Estrogenic Influences on Auditory Processing of Communication Signals within a Socio-Neuro-Endocrine Framework

PubMed Central

Yoder, Kathleen M.; Vicario, David S.

2012-01-01

Gonadal hormones modulate behavioral responses to sexual stimuli, and communication signals can also modulate circulating hormone levels. In several species, these combined effects appear to underlie a two-way interaction between circulating gonadal hormones and behavioral responses to socially salient stimuli. Recent work in songbirds has shown that manipulating local estradiol levels in the auditory forebrain produces physiological changes that affect discrimination of conspecific vocalizations and can affect behavior. These studies provide new evidence that estrogens can directly alter auditory processing and indirectly alter the behavioral response to a stimulus. These studies show that: 1. Local estradiol action within an auditory area is necessary for socially-relevant sounds to induce normal physiological responses in the brains of both sexes; 2. These physiological effects occur much more quickly than predicted by the classical time-frame for genomic effects; 3. Estradiol action within the auditory forebrain enables behavioral discrimination among socially-relevant sounds in males; and 4. Estradiol is produced locally in the male brain during exposure to particular social interactions. The accumulating evidence suggests a socio-neuro-endocrinology framework in which estradiol is essential to auditory processing, is increased by a socially relevant stimulus, acts rapidly to shape perception of subsequent stimuli experienced during social interactions, and modulates behavioral responses to these stimuli. Brain estrogens are likely to function similarly in both songbird sexes because aromatase and estrogen receptors are present in both male and female forebrain. Estrogenic modulation of perception in songbirds and perhaps other animals could fine-tune male advertising signals and female ability to discriminate them, facilitating mate selection by modulating behaviors. Keywords: Estrogens, Songbird, Social Context, Auditory Perception PMID:22201281

Something black in the American Psyche: formal innovation and Freudian imagery in the comics of Winsor McCay and Robert Crumb.

PubMed

Shannon, Edward A

2010-01-01

Winsor McCay’s Little Nemo in Slumberland anticipates Robert Crumb’s work. McCay’s innocent dreamscapes seem antithetical to the sexually explicit work of anti-capitalist Crumb, but Nemo looks forward to Crumb in subject and form. Nemo’s presentation of class, gender, and race, and its pre-Freudian sensibility are ironic counterpoints to Crumb’s political, Freudian comix.

Ballasted photovoltaic module and module arrays

DOEpatents

Botkin, Jonathan [El Cerrito, CA; Graves, Simon [Berkeley, CA; Danning, Matt [Oakland, CA

2011-11-29

A photovoltaic (PV) module assembly including a PV module and a ballast tray. The PV module includes a PV device and a frame. A PV laminate is assembled to the frame, and the frame includes an arm. The ballast tray is adapted for containing ballast and is removably associated with the PV module in a ballasting state where the tray is vertically under the PV laminate and vertically over the arm to impede overt displacement of the PV module. The PV module assembly can be installed to a flat commercial rooftop, with the PV module and the ballast tray both resting upon the rooftop. In some embodiments, the ballasting state includes corresponding surfaces of the arm and the tray being spaced from one another under normal (low or no wind) conditions, such that the frame is not continuously subjected to a weight of the tray.

Features of anti-inflammatory effects of modulated extremely high-frequency electromagnetic radiation.

PubMed

Gapeyev, Andrew B; Mikhailik, Elena N; Chemeris, Nikolay K

2009-09-01

Using a model of acute zymosan-induced paw edema in NMRI mice, we test the hypothesis that anti-inflammatory effects of extremely high-frequency electromagnetic radiation (EHF EMR) can be essentially modified by application of pulse modulation with certain frequencies. It has been revealed that a single exposure of animals to continuous EHF EMR for 20 min reduced the exudative edema of inflamed paw on average by 19% at intensities of 0.1-0.7 mW/cm(2) and frequencies from the range of 42.2-42.6 GHz. At fixed effective carrier frequency of 42.2 GHz, the anti-inflammatory effect of EHF EMR did not depend on modulation frequencies, that is, application of different modulation frequencies from the range of 0.03-100 Hz did not lead to considerable changes in the effect level. On the contrary, at "ineffective" carrier frequencies of 43.0 and 61.22 GHz, the use of modulation frequencies of 0.07-0.1 and 20-30 Hz has allowed us to restore the effect up to a maximal level. The results obtained show the critical dependence of anti-inflammatory action of low-intensity EHF EMR on carrier and modulation frequencies. Within the framework of this study, the possibility of changing the level of expected biological effect of modulated EMR by a special selection of combination of carrier and modulation frequencies is confirmed.

Artifacts and essentialism

PubMed Central

Gelman, Susan A.

2013-01-01

Psychological essentialism is an intuitive folk belief positing that certain categories have a non-obvious inner “essence” that gives rise to observable features. Although this belief most commonly characterizes natural kind categories, I argue that psychological essentialism can also be extended in important ways to artifact concepts. Specifically, concepts of individual artifacts include the non-obvious feature of object history, which is evident when making judgments regarding authenticity and ownership. Classic examples include famous works of art (e.g., the Mona Lisa is authentic because of its provenance), but ordinary artifacts likewise receive value from their history (e.g., a worn and tattered blanket may have special value if it was one's childhood possession). Moreover, in some cases, object history may be thought to have causal effects on individual artifacts, much as an animal essence has causal effects. I review empirical support for these claims and consider the implications for both artifact concepts and essentialism. This perspective suggests that artifact concepts cannot be contained in a theoretical framework that focuses exclusively on similarity or even function. Furthermore, although there are significant differences between essentialism of natural kinds and essentialism of artifact individuals, the commonalities suggest that psychological essentialism may not derive from folk biology but instead may reflect more domain-general perspectives on the world. PMID:23976903

Solar concentrator modules with silicone-onglass Fresnel lens panels and multijunction cells.

PubMed

Rumyantsev, Valery D

2010-04-26

High-efficiency multijunction (MJ) solar cells, being very expensive to manufacture, should only be used in combination with solar concentrators in terrestrial applications. An essential cost reduction of electric power produced by photovoltaic (PV) installations with MJ cells, may be expected by the creation of highly-effective, but inexpensive, elements for optical concentration and sun tracking. This article is an overview of the corresponding approach under development at the Ioffe Physical Technical Institute. The approach to R&D of the solar PV modules is based on the concepts of sunlight concentration by small-aperture area Fresnel lenses and "all-glass" module design. The small-aperture area lenses are arranged as a panel with silicone-on-glass structure where the glass plate serves as the front surface of a module. In turn, high-efficiency InGaP/(In)GaAs/Ge cells are arranged on a rear module panel mounted on a glass plate which functions as a heat sink and integrated protective cover for the cells. The developed PV modules and sun trackers are characterized by simple design, and are regarded as the prototypes for further commercialization.

Photovoltaic module and interlocked stack of photovoltaic modules

DOEpatents

Wares, Brian S.

2014-09-02

One embodiment relates to an arrangement of photovoltaic modules configured for transportation. The arrangement includes a plurality of photovoltaic modules, each photovoltaic module including a frame. A plurality of individual male alignment features and a plurality of individual female alignment features are included on each frame. Adjacent photovoltaic modules are interlocked by multiple individual male alignment features on a first module of the adjacent photovoltaic modules fitting into and being surrounded by corresponding individual female alignment features on a second module of the adjacent photovoltaic modules. Other embodiments, features and aspects are also disclosed.

Discovery and therapeutic promise of selective androgen receptor modulators.

PubMed

Chen, Jiyun; Kim, Juhyun; Dalton, James T

2005-06-01

Androgens are essential for male development and the maintenance of male secondary characteristics, such as bone mass, muscle mass, body composition, and spermatogenesis. The main disadvantages of steroidal androgens are their undesirable physicochemical and pharmacokinetic properties. The recent discovery of nonsteroidal selective androgen receptor modulators (SARMs) provides a promising alternative for testosterone replacement therapies with advantages including oral bioavailability, flexibility of structural modification, androgen receptor specificity, tissue selectivity, and the lack of steroid-related side effects.

Discovery AND Therapeutic Promise OF Selective Androgen Receptor Modulators

PubMed Central

Chen, Jiyun; Kim, Juhyun; Dalton, James T.

2007-01-01

Androgens are essential for male development and the maintenance of male secondary characteristics, such as bone mass, muscle mass, body composition, and spermatogenesis. The main disadvantages of steroidal androgens are their undesirable physicochemical and pharmacokinetic properties. The recent discovery of nonsteroidal selective androgen receptor modulators (SARMs) provides a promising alternative for testosterone replacement therapies with advantages including oral bioavailability, flexibility of structural modification, androgen receptor specificity, tissue selectivity, and the lack of steroid-related side effects. PMID:15994457

Numerical Modeling of Nanoelectronic Devices

NASA Technical Reports Server (NTRS)

Klimeck, Gerhard; Oyafuso, Fabiano; Bowen, R. Chris; Boykin, Timothy

2003-01-01

Nanoelectronic Modeling 3-D (NEMO 3-D) is a computer program for numerical modeling of the electronic structure properties of a semiconductor device that is embodied in a crystal containing as many as 16 million atoms in an arbitrary configuration and that has overall dimensions of the order of tens of nanometers. The underlying mathematical model represents the quantummechanical behavior of the device resolved to the atomistic level of granularity. The system of electrons in the device is represented by a sparse Hamiltonian matrix that contains hundreds of millions of terms. NEMO 3-D solves the matrix equation on a Beowulf-class cluster computer, by use of a parallel-processing matrix vector multiplication algorithm coupled to a Lanczos and/or Rayleigh-Ritz algorithm that solves for eigenvalues. In a recent update of NEMO 3-D, a new strain treatment, parameterized for bulk material properties of GaAs and InAs, was developed for two tight-binding submodels. The utility of the NEMO 3-D was demonstrated in an atomistic analysis of the effects of disorder in alloys and, in particular, in bulk In(x)Ga(l-x)As and in In0.6Ga0.4As quantum dots.

High-Reliability Pump Module for Non-Planar Ring Oscillator Laser

NASA Technical Reports Server (NTRS)

Liu, Duncan T.; Qiu, Yueming; Wilson, Daniel W.; Dubovitsky, Serge; Forouhar, Siamak

2007-01-01

We propose and have demonstrated a prototype high-reliability pump module for pumping a Non-Planar Ring Oscillator (NPRO) laser suitable for space missions. The pump module consists of multiple fiber-coupled single-mode laser diodes and a fiber array micro-lens array based fiber combiner. The reported Single-Mode laser diode combiner laser pump module (LPM) provides a higher normalized brightness at the combined beam than multimode laser diode based LPMs. A higher brightness from the pump source is essential for efficient NPRO laser pumping and leads to higher reliability because higher efficiency requires a lower operating power for the laser diodes, which in turn increases the reliability and lifetime of the laser diodes. Single-mode laser diodes with Fiber Bragg Grating (FBG) stabilized wavelength permit the pump module to be operated without a thermal electric cooler (TEC) and this further improves the overall reliability of the pump module. The single-mode laser diode LPM is scalable in terms of the number of pump diodes and is capable of combining hundreds of fiber-coupled laser diodes. In the proof-of-concept demonstration, an e-beam written diffractive micro lens array, a custom fiber array, commercial 808nm single mode laser diodes, and a custom NPRO laser head are used. The reliability of the proposed LPM is discussed.

Modules to enhance smart lighting education

NASA Astrophysics Data System (ADS)

Bunch, Robert M.; Joenathan, Charles; Connor, Kenneth; Chouikha, Mohamed

2012-10-01

Over the past several years there has been a rapid advancement in solid state lighting applications brought on by the development of high efficiency light emitting diodes. Development of lighting devices, systems and products that meet the demands of the future lighting marketplace requires workers from many disciplines including engineers, scientists, designers and architects. The National Science Foundation has recognized this fact and established the Smart Lighting Engineering Research Center that promotes research leading to smart lighting systems, partners with industry to enhance innovation and educates a diverse, world-class workforce. The lead institution is Rensselaer Polytechnic Institute with core partners Boston University and The University of New Mexico. Outreach partners include Howard University, Morgan State University, and Rose-Hulman Institute of Technology. Because of the multidisciplinary nature of advanced smart lighting systems workers often have little or no formal education in basic optics, lighting and illumination. This paper describes the initial stages of the development of self-contained and universally applicable educational modules that target essential optics topics needed for lighting applications. The modules are intended to be easily incorporated into new and existing courses by a variety of educators and/or to be used in a series of stand-alone, asynchronous training exercises by new graduate students. The ultimate goal of this effort is to produce resources such as video lectures, video presentations of students-teaching-students, classroom activities, assessment tools, student research projects and laboratories integrated into learning modules. Sample modules and resources will be highlighted. Other outreach activities such as plans for coursework, undergraduate research, design projects, and high school enrichment programs will be discussed.

Construction of a Bacterial Cell that Contains Only the Set of Essential Genes Necessary to Impart Life

DTIC Science & Technology

2014-08-15

characterized genes from Bacillus subtilis , that is presented in a constitutive expression module. If the B. subtilis gene containing M. mycoides mutant is...essential gene MMYC_0361 with the rlmH gene from Bacillus subtilis . Mycoplasma mycoides containing the B. subtilis rlmH was viable. This tells us the...viable than the function of the conserved hypothetical gene is the same as the input B. subtilis gene. Table of Contents: Section

Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial.

PubMed

Dummer, Reinhard; Schadendorf, Dirk; Ascierto, Paolo A; Arance, Ana; Dutriaux, Caroline; Di Giacomo, Anna Maria; Rutkowski, Piotr; Del Vecchio, Michele; Gutzmer, Ralf; Mandala, Mario; Thomas, Luc; Demidov, Lev; Garbe, Claus; Hogg, David; Liszkay, Gabriella; Queirolo, Paola; Wasserman, Ernesto; Ford, James; Weill, Marine; Sirulnik, L Andres; Jehl, Valentine; Bozón, Viviana; Long, Georgina V; Flaherty, Keith

2017-04-01

There are no established therapies specific for NRAS-mutant melanoma despite the emergence of immunotherapy. We aimed to assess the efficacy and safety of the MEK inhibitor binimetinib versus that of dacarbazine in patients with advanced NRAS-mutant melanoma. NEMO is an ongoing, randomised, open-label phase 3 study done at 118 hospitals in 26 countries. Patients with advanced, unresectable, American Joint Committee on Cancer stage IIIC or stage IV NRAS-mutant melanoma who were previously untreated or had progressed on or after previous immunotherapy were randomised (2:1) to receive either binimetinib 45 mg orally twice daily or dacarbazine 1000 mg/m 2 intravenously every 3 weeks. Randomisation was stratified by stage, performance status, and previous immunotherapy. The primary endpoint was progression-free survival assessed by blinded central review in the intention-to-treat population. Safety analyses were done in the safety population, consisting of all patients who received at least one study drug dose and one post-baseline safety assessment. This study is registered with ClinicalTrials.gov, number NCT01763164 and with EudraCT, number 2012-003593-51. Between Aug 19, 2013, and April 28, 2015, 402 patients were enrolled and randomly assigned, 269 to binimetinib and 133 to dacarbazine. Median follow-up was 1·7 months (IQR 1·4-4·1). Median progression-free survival was 2·8 months (95% CI 2·8-3·6) in the binimetinib group and 1·5 months (1·5-1·7) in the dacarbazine group (hazard ratio 0·62 [95% CI 0·47-0·80]; one-sided p<0·001). Grade 3-4 adverse events seen in at least 5% of patients the safety population in either group were increased creatine phosphokinase (52 [19%] of 269 patients in the binimetinib group vs none of 114 in the dacarbazine group), hypertension (20 [7%] vs two [2%]), anaemia (five [2%] vs six [5%]), and neutropenia (two [1%] vs ten [9%]). Serious adverse events (all grades) occurred in 91 (34%) patients in the binimetinib group and 25

Exploring Pharmacological Mechanisms of Lavender (Lavandula angustifolia) Essential Oil on Central Nervous System Targets

PubMed Central

López, Víctor; Nielsen, Birgitte; Solas, Maite; Ramírez, Maria J.; Jäger, Anna K.

2017-01-01

Lavender essential oil is traditionally used and approved by the European Medicines Agency (EMA) as herbal medicine to relieve stress and anxiety. Some animal and clinical studies reveal positive results in models of anxiety and depression although very little research has been done on molecular mechanisms. Our work consisted of evaluating the effects of lavender (Lavandula angustifolia) essential oil on central nervous system well-established targets, such as MAO-A, SERT, GABAAand NMDA receptors as well as in vitro models of neurotoxicity. The results showed that lavender essential oil and its main components exert affinity for the glutamate NMDA-receptor in a dose-dependent manner with an IC50 value of 0.04 μl/mL for lavender oil. In addition, lavender and linalool were also able to bind the serotonin transporter (SERT) whereas they did not show affinity for GABAA-benzodiazepine receptor. In three different models of neurotoxicity, lavender did not enhance the neurotoxic insult and improved viability of SH-SY5Y cells treated with hydrogen peroxide. According to our data, the anxiolytic and antidepressant-like effects attributed to lavender may be due to an antagonism on the NMDA-receptor and inhibition of SERT. This study suggests that lavender essential oil may exert pharmacological properties via modulating the NMDA receptor, the SERT as well as neurotoxicity induced by hydrogen peroxide. PMID:28579958

Thermo-mechanical actuator-based miniature tagging module for localization in capsule endoscopy

NASA Astrophysics Data System (ADS)

Chandrappan, Jayakrishnan; Ruiqi, Lim; Su, Nandar; Yen Yi, Germaine Hoe; Vaidyanathan, Kripesh

2011-04-01

Capsule endoscopy is a frontline medical diagnostic tool for the gastro intestinal tract disorders. During diagnosis, efficient localization techniques are essential to specify a pathological area that may require further diagnosis or treatment. This paper presents the development of a miniature tagging module that relies on a novel concept to label the region of interest and has the potential to integrate with a capsule endoscope. The tagging module is a compact thermo-mechanical actuator loaded with a biocompatible micro tag. A low power microheater attached to the module serves as the thermal igniter for the mechanical actuator. At optimum temperature, the actuator releases the micro tag instantly and penetrates the mucosa layer of a GI tract, region of interest. Ex vivo animal trials are conducted to verify the feasibility of the tagging module concept. X-ray imaging is used to detect the location of the micro tag embedded in the GI tract wall. The method is successful, and radiopaque micro tags can provide valuable pre-operative position information on the infected area to facilitate further clinical procedures.

Fast kinase domain-containing protein 3 is a mitochondrial protein essential for cellular respiration

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

Simarro, Maria; Gimenez-Cassina, Alfredo; Kedersha, Nancy

2010-10-22

Research highlights: {yields} Five members of the FAST kinase domain-containing proteins are localized to mitochondria in mammalian cells. {yields} The FASTKD3 interactome includes proteins involved in various aspects of mitochondrial metabolism. {yields} Targeted knockdown of FASTKD3 significantly reduces basal and maximal mitochondrial oxygen consumption. -- Abstract: Fas-activated serine/threonine phosphoprotein (FAST) is the founding member of the FAST kinase domain-containing protein (FASTKD) family that includes FASTKD1-5. FAST is a sensor of mitochondrial stress that modulates protein translation to promote the survival of cells exposed to adverse conditions. Mutations in FASTKD2 have been linked to a mitochondrial encephalomyopathy that is associated withmore » reduced cytochrome c oxidase activity, an essential component of the mitochondrial electron transport chain. We have confirmed the mitochondrial localization of FASTKD2 and shown that all FASTKD family members are found in mitochondria. Although human and mouse FASTKD1-5 genes are expressed ubiquitously, some of them are most abundantly expressed in mitochondria-enriched tissues. We have found that RNA interference-mediated knockdown of FASTKD3 severely blunts basal and stress-induced mitochondrial oxygen consumption without disrupting the assembly of respiratory chain complexes. Tandem affinity purification reveals that FASTKD3 interacts with components of mitochondrial respiratory and translation machineries. Our results introduce FASTKD3 as an essential component of mitochondrial respiration that may modulate energy balance in cells exposed to adverse conditions by functionally coupling mitochondrial protein synthesis to respiration.« less

Reaching consensus: a review on sexual health training modules for professional capacity building.

PubMed

Karimian, Zahra; Azin, Seied Ali; Javid, Nasrin; Araban, Marzieh; Maasoumi, Raziyeh; Aghayan, Shahrokh; Merghati Khoie, Effat

2018-01-01

Background: Professional capacity building (PCB) is the focus point in health-related subjects.The present study was conducted to systematically review the existing sexual health training modules for health care providers. Methods: The following keywords were used to search: training, education, professional capacity, practitioner, sexual health, skill education, module, course, package and curriculum.The term MESH is referred to Medical Subject Headings and the following databases were investigated: MEDLINE, EMBASE, PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), The Cochrane Library and Web of Science, Scopus, Google Scholar, SID,Magiran, and Iranmedex. All articles from 1980 to 2015 were extracted. Online modules were excluded. Considering that lesson plan was the basis of instruction, the modules were selected based on the characteristics of the lesson plans. Results: A total number of 38 published training modules in the field of sexuality we redetermined. In total, more than half of the modules (58%) were designed for medical doctor sand allied health professionals and the remaining (42%) were for nurses and midwives. Almost all the modules (97%) were introduced and utilized in developed countries, and only 3% were disseminated in developing countries. Conclusion: There are invaluable modules to build professional capacity in the field of sexual health. As a number of modules have been designed for nurses and midwifes, as the first-line health care providers, the use of these groups in sexual counseling and empowerment for sexual health is essential. No sexual health training program was designed in Iran. Therefore, designing such modules according to Iranian culture is strongly recommended.

Reaching consensus: a review on sexual health training modules for professional capacity building

PubMed Central

Karimian, Zahra; Azin, Seied Ali; Javid, Nasrin; Araban, Marzieh; Maasoumi, Raziyeh; Aghayan, Shahrokh; Merghati Khoie, Effat

2018-01-01

Background: Professional capacity building (PCB) is the focus point in health-related subjects.The present study was conducted to systematically review the existing sexual health training modules for health care providers. Methods: The following keywords were used to search: training, education, professional capacity, practitioner, sexual health, skill education, module, course, package and curriculum.The term MESH is referred to Medical Subject Headings and the following databases were investigated: MEDLINE, EMBASE, PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), The Cochrane Library and Web of Science, Scopus, Google Scholar, SID,Magiran, and Iranmedex. All articles from 1980 to 2015 were extracted. Online modules were excluded. Considering that lesson plan was the basis of instruction, the modules were selected based on the characteristics of the lesson plans. Results: A total number of 38 published training modules in the field of sexuality we redetermined. In total, more than half of the modules (58%) were designed for medical doctor sand allied health professionals and the remaining (42%) were for nurses and midwives. Almost all the modules (97%) were introduced and utilized in developed countries, and only 3% were disseminated in developing countries. Conclusion: There are invaluable modules to build professional capacity in the field of sexual health. As a number of modules have been designed for nurses and midwifes, as the first-line health care providers, the use of these groups in sexual counseling and empowerment for sexual health is essential. No sexual health training program was designed in Iran. Therefore, designing such modules according to Iranian culture is strongly recommended. PMID:29423357

Locus coeruleus phasic discharge is essential for stimulus-induced gamma oscillations in the prefrontal cortex.

PubMed

Neves, Ricardo M; van Keulen, Silvia; Yang, Mingyu; Logothetis, Nikos K; Eschenko, Oxana

2018-03-01

The locus coeruleus (LC) noradrenergic (NE) neuromodulatory system is critically involved in regulation of neural excitability via its diffuse ascending projections. Tonic NE release in the forebrain is essential for maintenance of vigilant states and increases the signal-to-noise ratio of cortical sensory responses. The impact of phasic NE release on cortical activity and sensory processing is less explored. We previously reported that LC microstimulation caused a transient desynchronization of population activity in the medial prefrontal cortex (mPFC), similar to noxious somatosensory stimuli. The LC receives nociceptive information from the medulla and therefore may mediate sensory signaling to its forebrain targets. Here we performed extracellular recordings in LC and mPFC while presenting noxious stimuli in urethane-anesthetized rats. A brief train of foot shocks produced a robust phasic response in the LC and a transient change in the mPFC power spectrum, with the strongest modulation in the gamma (30-90 Hz) range. The LC phasic response preceded prefrontal gamma power increase, and cortical modulation was proportional to the LC excitation. We also quantitatively characterized distinct cortical states and showed that sensory responses in both LC and mPFC depend on the ongoing cortical state. Finally, cessation of the LC firing by bilateral local iontophoretic injection of clonidine, an α 2 -adrenoreceptor agonist, completely eliminated sensory responses in the mPFC without shifting cortex to a less excitable state. Together, our results suggest that the LC phasic response induces gamma power increase in the PFC and is essential for mediating sensory information along an ascending noxious pathway. NEW & NOTEWORTHY Our study shows linear relationships between locus coeruleus phasic excitation and the amplitude of gamma oscillations in the prefrontal cortex. Results suggest that the locus coeruleus phasic response is essential for mediating sensory information

Rational Basis for the Use of Bergamot Essential Oil in Complementary Medicine to Treat Chronic Pain.

PubMed

Rombolà, L; Amantea, D; Russo, R; Adornetto, A; Berliocchi, L; Tridico, L; Corasaniti, M T; Sakurada, S; Sakurada, T; Bagetta, G; Morrone, L A

2016-01-01

In complementary medicine, aromatherapy uses essential oils to improve agitation and aggression observed in dementia, mood, depression, anxiety and chronic pain. Preclinical research studies have reported that the essential oil obtained from bergamot (BEO) fruit (Citrus bergamia, Risso) modifies normal and pathological synaptic plasticity implicated, for instance, in nociceptive and neuropathic pain. Interestingly, recent results indicated that BEO modulates sensitive perception of pain in different models of nociceptive, inflammatory and neuropathic pain modulating endogenous systems. Thus, local administration of BEO inhibited the nociceptive behavioral effect induced by intraplantar injection of capsaicin or formalin in mice. Similar effects were observed with linalool and linalyl acetate, major volatile components of the phytocomplex, Pharmacological studies showed that the latter effects are reversed by local or systemic pretreatment with the opioid antagonist naloxone hydrochloride alike with naloxone methiodide, high affinity peripheral μ-opioid receptor antagonist. These results and the synergistic effect observed following systemic or intrathecal injection of an inactive dose of morphine with BEO or linalool indicated an activation of peripheral opioid system. Recently, in neuropathic pain models systemic or local administration of BEO or linalool induced antiallodynic effects. In particular, in partial sciatic nerve ligation (PSNL) model, intraplantar injection of the phytocomplex or linalool in the ipsilateral hindpaw, but not in the contralateral, reduced PSNL-induced extracellularsignal- regulated kinase (ERK) activation and mechanical allodynia. In neuropathic pain high doses of morphine are needed to reduce pain. Interestingly, combination of inactive doses of BEO or linalool with a low dose of morphine induced antiallodynic effects in mice. Peripheral cannabinoid and opioid systems appear to be involved in the antinociception produced by

On Functional Module Detection in Metabolic Networks

PubMed Central

Koch, Ina; Ackermann, Jörg

2013-01-01

Functional modules of metabolic networks are essential for understanding the metabolism of an organism as a whole. With the vast amount of experimental data and the construction of complex and large-scale, often genome-wide, models, the computer-aided identification of functional modules becomes more and more important. Since steady states play a key role in biology, many methods have been developed in that context, for example, elementary flux modes, extreme pathways, transition invariants and place invariants. Metabolic networks can be studied also from the point of view of graph theory, and algorithms for graph decomposition have been applied for the identification of functional modules. A prominent and currently intensively discussed field of methods in graph theory addresses the Q-modularity. In this paper, we recall known concepts of module detection based on the steady-state assumption, focusing on transition-invariants (elementary modes) and their computation as minimal solutions of systems of Diophantine equations. We present the Fourier-Motzkin algorithm in detail. Afterwards, we introduce the Q-modularity as an example for a useful non-steady-state method and its application to metabolic networks. To illustrate and discuss the concepts of invariants and Q-modularity, we apply a part of the central carbon metabolism in potato tubers (Solanum tuberosum) as running example. The intention of the paper is to give a compact presentation of known steady-state concepts from a graph-theoretical viewpoint in the context of network decomposition and reduction and to introduce the application of Q-modularity to metabolic Petri net models. PMID:24958145

Composition, anti-quorum sensing and antimicrobial activity of essential oils from Lippia alba

PubMed Central

Olivero-Verbel, Jesus; Barreto-Maya, Ana; Bertel-Sevilla, Angela; Stashenko, Elena E.

2014-01-01

Many Gram-negative pathogens have the ability to produce N-acylhomoserine lactones (AHLs) as signal molecules for quorum sensing (QS). This cell-cell communication system allows them to coordinate gene expression and regulate virulence. Strategies to inhibit QS are promising for the control of infectious diseases or antibiotic resistant bacterial pathogens. The aim of the present study was to evaluate the anti-quorum sensing (anti-QS) and antibacterial potential of five essential oils isolated from Lippia alba on the Tn-5 mutant of Chromobacterium violaceum CV026, and on the growth of the gram-positive bacteria S. aureus ATCC 25923. The anti-QS activity was detected through the inhibition of the QS-controlled violacein pigment production by the sensor bacteria. Results showed that two essential oils from L. alba, one containing the greatest geranial:neral and the other the highest limonene:carvone concentrations, were the most effective QS inhibitors. Both oils also had small effects on cell growth. Moreover, the geranial/neral chemotype oil also produced the maximum zone of growth inhibition against S. aureus ATCC 25923. These data suggest essential oils from L. alba have promising properties as QS modulators, and present antibacterial activity on S. aureus. PMID:25477905

Down-modulation of receptors for phorbol ester tumor promoter in primary epidermal cells

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

Solanki, V.; Slaga, T.J.

1982-01-01

The specific (20-/sup 3/H)phorbol 12,13-dibutyrate ((/sup 3/H)PDBu) binding to intact epidermal cells displayed the phenomenon of down-modulation, i.e., the specific binding of (/sup 3/H)PDBu to its receptors on primary epidermal cells reached a maximum within 1 h and steadily declined thereafter. The apparent down-modulation of radiolabel resulted from a partial loss in the total number of receptors; the affinity of receptors for the ligand was essentially unchanged. A number of agents such as chloroquine, methylamine, or arginine which are known to prevent clustering, down-modulation, and/or internalization of several hormone receptors did not affect the down-modulation of phorbol ester receptors. Furthermore,more » cycloheximide had no effect either on down-modulation or on the binding capacity of cells. The surface binding capacity of down-modulated cells following a 90-min incubation with unlabeled ligand was almost returned to normal within 1 h. The effect of the antidepressant drug chlorpromazine, which is known to interact with calmodulin, on (/sup 3/H)PDBu binding was also investigated. Our data indicate that the effect of chlorpromazine on (/sup 3/H)PDBu binding is probably unrelated to its calmodulin-binding activity.« less

A Phase I Clinical Trial of Systemically Delivered NEMO Binding Domain Peptide in Dogs with Spontaneous Activated B-Cell like Diffuse Large B-Cell Lymphoma

PubMed Central

Habineza Ndikuyeze, Georges; Gaurnier-Hausser, Anita; Patel, Reema; Baldwin, Albert S.; May, Michael J.; Flood, Patrick; Krick, Erika; Propert, Kathleen J.; Mason, Nicola J.

2014-01-01

Activated B-Cell (ABC) Diffuse Large B-Cell Lymphoma (DLBCL) is a common, aggressive and poorly chemoresponsive subtype of DLBCL, characterized by constitutive canonical NF-κB signaling. Inhibition of NF-κB signaling leads to apoptosis of ABC-DLBCL cell lines, suggesting targeted disruption of this pathway may have therapeutic relevance. The selective IKK inhibitor, NEMO Binding Domain (NBD) peptide effectively blocks constitutive NF-κB activity and induces apoptosis in ABC-DLBCL cells in vitro. Here we used a comparative approach to determine the safety and efficacy of systemic NBD peptide to inhibit constitutive NF-κB signaling in privately owned dogs with spontaneous newly diagnosed or relapsed ABC-like DLBCL. Malignant lymph nodes biopsies were taken before and twenty-four hours after peptide administration to determine biological effects. Intravenous administration of <2 mg/kg NBD peptide was safe and inhibited constitutive canonical NF-κB activity in 6/10 dogs. Reductions in mitotic index and Cyclin D expression also occurred in a subset of dogs 24 hours post peptide and in 3 dogs marked, therapeutically beneficial histopathological changes were identified. Mild, grade 1 toxicities were noted in 3 dogs at the time of peptide administration and one dog developed transient subclinical hepatopathy. Long term toxicities were not identified. Pharmacokinetic data suggested rapid uptake of peptide into tissues. No significant hematological or biochemical toxicities were identified. Overall the results from this phase I study indicate that systemic administration of NBD peptide is safe and effectively blocks constitutive NF-κB signaling and reduces malignant B cell proliferation in a subset of dogs with ABC-like DLBCL. These results have potential translational relevance for human ABC-DLBCL. PMID:24798348

Very-low-power and footprint integrated photonic modulators and switches for ICT

NASA Astrophysics Data System (ADS)

Thylén, Lars; Holmström, Petter; Wosinski, Lech

2013-03-01

The current development in photonics for communications and interconnects pose increasing requirements on reduction of footprint, power dissipation and cost, as well as increased bandwidth. Integrated nanophotonics has been viewed as one solution to this, capitalizing on development in nanotechnology as such as well as on increased insights into light matter interaction on the nanoscale. The latter can be exemplified by plasmonics and low-dimensional semiconductors such as quantum dots (QDs). In this scenario the development of better electrooptic materials is also of great importance, the electrooptic polymers being an example, since they potentially offer improved properties for optical phase modulators in terms of power and probably cost and general flexibility. Phase modulators are essential for e.g. the rapidly developing advanced modulation formats for telecom, since phase modulation basically can generate any type of modulation. The electrooptic polymers, e.g. in combination with plasmonics nanoparticle array waveguides or nanostructured hybrid plasmonic media can theoretically give extremely compact and low power dissipation modulators, still to be demonstrated. The low-dimensional semiconductors, e.g. in the shape of QDs, can be employed for modulation or switching functions, offering possibilities in the future for scaling to 2 or 3 dimensions for advanced switching functions. In both the plasmonics and QD cases, nanosizing and low power dissipation are generally due to near-field interactions, albeit being of different physical origin in the two cases. A comparison of all-optical and electronically controlled switching is given.

An Extensive Unified Thermo-Electric Module Characterization Method

PubMed Central

Attivissimo, Filippo; Guarnieri Calò Carducci, Carlo; Lanzolla, Anna Maria Lucia; Spadavecchia, Maurizio

2016-01-01

Thermo-Electric Modules (TEMs) are being increasingly used in power generation as a valid alternative to batteries, providing autonomy to sensor nodes or entire Wireless Sensor Networks, especially for energy harvesting applications. Often, manufacturers provide some essential parameters under determined conditions, like for example, maximum temperature difference between the surfaces of the TEM or for maximum heat absorption, but in many cases, a TEM-based system is operated under the best conditions only for a fraction of the time, thus, when dynamic working conditions occur, the performance estimation of TEMs is crucial to determine their actual efficiency. The focus of this work is on using a novel procedure to estimate the parameters of both the electrical and thermal equivalent model and investigate their relationship with the operating temperature and the temperature gradient. The novelty of the method consists in the use of a simple test configuration to stimulate the modules and simultaneously acquire electrical and thermal data to obtain all parameters in a single test. Two different current profiles are proposed as possible stimuli, which use depends on the available test instrumentation, and relative performance are compared both quantitatively and qualitatively, in terms of standard deviation and estimation uncertainty. Obtained results, besides agreeing with both technical literature and a further estimation method based on module specifications, also provides the designer a detailed description of the module behavior, useful to simulate its performance in different scenarios. PMID:27983575

An Extensive Unified Thermo-Electric Module Characterization Method.

PubMed

Attivissimo, Filippo; Guarnieri Calò Carducci, Carlo; Lanzolla, Anna Maria Lucia; Spadavecchia, Maurizio

2016-12-13

Thermo-Electric Modules (TEMs) are being increasingly used in power generation as a valid alternative to batteries, providing autonomy to sensor nodes or entire Wireless Sensor Networks, especially for energy harvesting applications. Often, manufacturers provide some essential parameters under determined conditions, like for example, maximum temperature difference between the surfaces of the TEM or for maximum heat absorption, but in many cases, a TEM-based system is operated under the best conditions only for a fraction of the time, thus, when dynamic working conditions occur, the performance estimation of TEMs is crucial to determine their actual efficiency. The focus of this work is on using a novel procedure to estimate the parameters of both the electrical and thermal equivalent model and investigate their relationship with the operating temperature and the temperature gradient. The novelty of the method consists in the use of a simple test configuration to stimulate the modules and simultaneously acquire electrical and thermal data to obtain all parameters in a single test. Two different current profiles are proposed as possible stimuli, which use depends on the available test instrumentation, and relative performance are compared both quantitatively and qualitatively, in terms of standard deviation and estimation uncertainty. Obtained results, besides agreeing with both technical literature and a further estimation method based on module specifications, also provides the designer a detailed description of the module behavior, useful to simulate its performance in different scenarios.

Prostanoids and their receptors that modulate dendritic cell-mediated immunity.

PubMed

Gualde, Norbert; Harizi, Hedi

2004-08-01

Dendritic cells (DC) are essential for the initiation of immune responses by capturing, processing and presenting antigens to T cells. In addition to their important role as professional APC, they are able to produce immunosuppressive and pro-inflammatory prostanoids from arachidonic acid (AA) by the action of cyclooxygenase (COX) enzymes. In an autocrine and paracrine fashion, the secreted lipid mediators subsequently modulate the maturation, cytokine production, Th-cell polarizing ability, chemokine receptor expression, migration, and apoptosis of these extremely versatile APC. The biological actions of prostanoids, including their effects on APC-mediated immunity and acute inflammatory responses, are exerted by G protein-coupled receptors on plasma membrane. Some COX metabolites act as anti-inflammatory lipid mediators by binding to nuclear receptors and modulating DC functions. Although the role of cytokines in DC function has been studied extensively, the effects of prostanoids on DC biology have only recently become the focus of investigation. This review summarizes the current knowledge about the role of prostanoids and their receptors in modulating DC function and the subsequent immune responses.

Solar concentrator modules with silicone-on-glass Fresnel lens panels and multijunction cells.

PubMed

Rumyantsev, Valery D

2010-04-26

High-efficiency multijunction (MJ) solar cells, being very expensive to manufacture, should only be used in combination with solar concentrators in terrestrial applications. An essential cost reduction of electric power produced by photovoltaic (PV) installations with MJ cells, may be expected by the creation of highly-effective, but inexpensive, elements for optical concentration and sun tracking. This article is an overview of the corresponding approach under development at the Ioffe Physical Technical Institute. The approach to R&D of the solar PV modules is based on the concepts of sunlight concentration by small-aperture area Fresnel lenses and "all-glass" module design. The small-aperture area lenses are arranged as a panel with silicone-on-glass structure where the glass plate serves as the front surface of a module. In turn, high-efficiency InGaP/(In)GaAs/Ge cells are arranged on a rear module panel mounted on a glass plate which functions as a heat sink and integrated protective cover for the cells. The developed PV modules and sun trackers are characterized by simple design, and are regarded as the prototypes for further commercialization.

A Modularity-Based Method Reveals Mixed Modules from Chemical-Gene Heterogeneous Network

PubMed Central

Song, Jianglong; Tang, Shihuan; Liu, Xi; Gao, Yibo; Yang, Hongjun; Lu, Peng

2015-01-01

For a multicomponent therapy, molecular network is essential to uncover its specific mode of action from a holistic perspective. The molecular system of a Traditional Chinese Medicine (TCM) formula can be represented by a 2-class heterogeneous network (2-HN), which typically includes chemical similarities, chemical-target interactions and gene interactions. An important premise of uncovering the molecular mechanism is to identify mixed modules from complex chemical-gene heterogeneous network of a TCM formula. We thus proposed a novel method (MixMod) based on mixed modularity to detect accurate mixed modules from 2-HNs. At first, we compared MixMod with Clauset-Newman-Moore algorithm (CNM), Markov Cluster algorithm (MCL), Infomap and Louvain on benchmark 2-HNs with known module structure. Results showed that MixMod was superior to other methods when 2-HNs had promiscuous module structure. Then these methods were tested on a real drug-target network, in which 88 disease clusters were regarded as real modules. MixMod could identify the most accurate mixed modules from the drug-target 2-HN (normalized mutual information 0.62 and classification accuracy 0.4524). In the end, MixMod was applied to the 2-HN of Buchang naoxintong capsule (BNC) and detected 49 mixed modules. By using enrichment analysis, we investigated five mixed modules that contained primary constituents of BNC intestinal absorption liquid. As a matter of fact, the findings of in vitro experiments using BNC intestinal absorption liquid were found to highly accord with previous analysis. Therefore, MixMod is an effective method to detect accurate mixed modules from chemical-gene heterogeneous networks and further uncover the molecular mechanism of multicomponent therapies, especially TCM formulae. PMID:25927435

Construction of a Bacterial Cell that Contains Only the Set of Essential Genes Necessary to Impart Life

DTIC Science & Technology

2014-05-16

native uncharacterized genes for characterized genes from Bacillus subtilis , that is presented in a constitutive expression module. If the B... subtilis gene containing M. mycoides mutant is viable than the function of the conserved hypothetical gene is the same as the input B. subtilis gene...Characterized genes from B. subtilis were swapped with similar, but not so similar as to be clearly the same, essential genes from M. mycoides. The B. subtilis

Essential role of B-Raf in ERK activation during extraembryonic development.

PubMed

Galabova-Kovacs, Gergana; Matzen, Dana; Piazzolla, Daniela; Meissl, Katrin; Plyushch, Tatiana; Chen, Adele P; Silva, Alcino; Baccarini, Manuela

2006-01-31

The kinases of the Raf family have been intensively studied as activators of the mitogen-activated protein kinase kinase/extra-cellular signal-regulated kinase (ERK) module in regulated and deregulated proliferation. Genetic evidence that Raf is required for ERK activation in vivo has been obtained in lower organisms, which express only one Raf kinase, but was hitherto lacking in mammals, which express more than one Raf kinase. Ablation of the two best studied Raf kinases, B-Raf and Raf-1, is lethal at midgestation in mice, hampering the detailed study of the essential functions of these proteins. Here, we have combined conventional and conditional gene ablation to show that B-Raf is essential for ERK activation and for vascular development in the placenta. B-Raf-deficient placentae show complete absence of phosphorylated ERK and strongly reduced HIF-1alpha and VEGF levels, whereas all these parameters are normal in Raf-1-deficient placentae. In addition, neither ERK phosphorylation nor development are affected in B-raf-deficient embryos that are born alive obtained by epiblast-restricted gene inactivation. The data demonstrate that B-Raf plays a nonredundant role in ERK activation during extraembyronic mammalian development in vivo.

Rare essentials: drugs for rare diseases as essential medicines.

PubMed

Stolk, Pieter; Willemen, Marjolein J C; Leufkens, Hubert G M

2006-09-01

Since 1977, the WHO Model List of Essential Medicines (EML), published by WHO, has provided advice for Member States that struggle to decide which pharmaceutical technologies should be provided to patients within their public health systems. Originating from outside WHO, an incentive system has been put in place by various governments for the development of medicines for rare diseases ("orphan drugs"). With progress in pharmaceutical research (e.g. drugs targeted for narrower indications), these medicines will feature more often on future public health agendas. However, when current definitions for selecting essential medicines are applied strictly, orphan drugs cannot be part of the WHO Essential Medicines Programme, creating the risk that WHO may lose touch with this field. In our opinion WHO should explicitly include orphan drugs in its policy sphere by composing a complementary Orphan Medicines Model List as an addition to the EML. This complementary list of "rare essentials" could aid policy-makers and patients in, for example, emerging countries to improve access to these drugs and stimulate relevant policies. Furthermore, inconsistencies in the current EML with regard to medicines for rare diseases can be resolved. In this paper we propose selection criteria for an Orphan Medicines Model List that could form a departure point for future work towards an extensive WHO Orphan Medicines Programme.

Rare essentials: drugs for rare diseases as essential medicines.

PubMed Central

Stolk, Pieter; Willemen, Marjolein J. C.; Leufkens, Hubert G. M.

2006-01-01

Since 1977, the WHO Model List of Essential Medicines (EML), published by WHO, has provided advice for Member States that struggle to decide which pharmaceutical technologies should be provided to patients within their public health systems. Originating from outside WHO, an incentive system has been put in place by various governments for the development of medicines for rare diseases ("orphan drugs"). With progress in pharmaceutical research (e.g. drugs targeted for narrower indications), these medicines will feature more often on future public health agendas. However, when current definitions for selecting essential medicines are applied strictly, orphan drugs cannot be part of the WHO Essential Medicines Programme, creating the risk that WHO may lose touch with this field. In our opinion WHO should explicitly include orphan drugs in its policy sphere by composing a complementary Orphan Medicines Model List as an addition to the EML. This complementary list of "rare essentials" could aid policy-makers and patients in, for example, emerging countries to improve access to these drugs and stimulate relevant policies. Furthermore, inconsistencies in the current EML with regard to medicines for rare diseases can be resolved. In this paper we propose selection criteria for an Orphan Medicines Model List that could form a departure point for future work towards an extensive WHO Orphan Medicines Programme. PMID:17128345

Modulation of Human Neutrophil Responses by the Essential Oils from Ferula akitschkensis and Their Constituents.

PubMed

Schepetkin, Igor A; Kushnarenko, Svetlana V; Özek, Gulmira; Kirpotina, Liliya N; Sinharoy, Pritam; Utegenova, Gulzhakhan A; Abidkulova, Karime T; Özek, Temel; Başer, Kemal Hüsnü Can; Kovrizhina, Anastasia R; Khlebnikov, Andrei I; Damron, Derek S; Quinn, Mark T

2016-09-28

Essential oils were obtained by hydrodistillation of the umbels+seeds and stems of Ferula akitschkensis (FAEOu/s and FAEOstm, respectively) and analyzed by gas chromatography and gas chromatography-mass spectrometry. Fifty-two compounds were identified in FAEOu/s; the primary components were sabinene, α-pinene, β-pinene, terpinen-4-ol, eremophilene, and 2-himachalen-7-ol, whereas the primary components of FAEOstm were myristicin and geranylacetone. FAEOu/s, β-pinene, sabinene, γ-terpinene, geranylacetone, isobornyl acetate, and (E)-2-nonenal stimulated [Ca(2+)]i mobilization in human neutrophils, with the most potent being geranylacetone (EC50 = 7.6 ± 1.9 μM) and isobornyl acetate 6.4 ± 1.7 (EC50 = 7.6 ± 1.9 μM). In addition, treatment of neutrophils with β-pinene, sabinene, γ-terpinene, geranylacetone, and isobornyl acetate desensitized the cells to N-formyl-Met-Leu-Phe (fMLF)- and interleukin-8 (IL-8)-induced [Ca(2+)]i flux and inhibited fMLF-induced chemotaxis. The effects of β-pinene, sabinene, γ-terpinene, geranylacetone, and isobornyl acetate on neutrophil [Ca(2+)]i flux were inhibited by transient receptor potential (TRP) channel blockers. Furthermore, the most potent compound, geranylacetone, activated Ca(2+) influx in TRPV1-transfected HEK293 cells. In contrast, myristicin inhibited neutrophil [Ca(2+)]i flux stimulated by fMLF and IL-8 and inhibited capsaicin-induced Ca(2+) influx in TRPV1-transfected HEK293 cells. These findings, as well as pharmacophore modeling of TRP agonists, suggest that geranylacetone is a TRPV1 agonist, whereas myristicin is a TRPV1 antagonist. Thus, at least part of the medicinal properties of Ferula essential oils may be due to modulatory effects on TRP channels.

Modulation of voice related to tremor and vibrato

NASA Astrophysics Data System (ADS)

Lester, Rosemary Anne

Modulation of voice is a result of physiologic oscillation within one or more components of the vocal system including the breathing apparatus (i.e., pressure supply), the larynx (i.e. sound source), and the vocal tract (i.e., sound filter). These oscillations may be caused by pathological tremor associated with neurological disorders like essential tremor or by volitional production of vibrato in singers. Because the acoustical characteristics of voice modulation specific to each component of the vocal system and the effect of these characteristics on perception are not well-understood, it is difficult to assess individuals with vocal tremor and to determine the most effective interventions for reducing the perceptual severity of the disorder. The purpose of the present studies was to determine how the acoustical characteristics associated with laryngeal-based vocal tremor affect the perception of the magnitude of voice modulation, and to determine if adjustments could be made to the voice source and vocal tract filter to alter the acoustic output and reduce the perception of modulation. This research was carried out using both a computational model of speech production and trained singers producing vibrato to simulate laryngeal-based vocal tremor with different voice source characteristics (i.e., vocal fold length and degree of vocal fold adduction) and different vocal tract filter characteristics (i.e., vowel shapes). It was expected that, by making adjustments to the voice source and vocal tract filter that reduce the amplitude of the higher harmonics, the perception of magnitude of voice modulation would be reduced. The results of this study revealed that listeners' perception of the magnitude of modulation of voice was affected by the degree of vocal fold adduction and the vocal tract shape with the computational model, but only by the vocal quality (corresponding to the degree of vocal fold adduction) with the female singer. Based on regression analyses

Electroacoustic verification of frequency modulation systems in cochlear implant users.

PubMed

Fidêncio, Vanessa Luisa Destro; Jacob, Regina Tangerino de Souza; Tanamati, Liége Franzini; Bucuvic, Érika Cristina; Moret, Adriane Lima Mortari

2017-12-26

the speech processor and the frequency modulation system gain are essential when fitting this device. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Modulation limit of semiconductor lasers by some parametric modulation schemes

NASA Astrophysics Data System (ADS)

Iga, K.

1985-07-01

Using the simple rate equations and small signal analysis, the modulation speed limit of semiconductor lasers with modulation schemes such as gain switching, modulation of nonradiative recombination lifetime of minority carriers, and cavity Q modulation, is calculated and compared with the injection modulation scheme of Ikegami and Suematsu (1968). It is found that the maximum modulation frequency for the gain and Q modulation can exceed the resonance-like frequency by a factor equal to the coefficient of the time derivative of the modulation parameter, though the nonradiative lifetime modulation is not shown to be different from the injection modulation. A solution for the carrier lifetime modulation of LED is obtained, and the possibility of wideband modulation in this scheme is demonstrated.

A prototype automatic phase compensation module

NASA Technical Reports Server (NTRS)

Terry, John D.

1992-01-01

The growing demands for high gain and accurate satellite communication systems will necessitate the utilization of large reflector systems. One area of concern of reflector based satellite communication is large scale surface deformations due to thermal effects. These distortions, when present, can degrade the performance of the reflector system appreciable. This performance degradation is manifested by a decrease in peak gain, and increase in sidelobe level, and pointing errors. It is essential to compensate for these distortion effects and to maintain the required system performance in the operating space environment. For this reason the development of a technique to offset the degradation effects is highly desirable. Currently, most research is direct at developing better material for the reflector. These materials have a lower coefficient of linear expansion thereby reducing the surface errors. Alternatively, one can minimize the distortion effects of these large scale errors by adaptive phased array compensation. Adaptive phased array techniques have been studied extensively at NASA and elsewhere. Presented in this paper is a prototype automatic phase compensation module designed and built at NASA Lewis Research Center which is the first stage of development for an adaptive array compensation module.

Inspiring Climate Education Excellence (ICEE): Developing self-directed professional development modules for secondary science teachers

NASA Astrophysics Data System (ADS)

Buhr, S. M.; Lynds, S. E.; McCaffrey, M. S.; Morton, E.

2010-12-01

Inspiring Climate Education Excellence (ICEE) is a NASA-funded project to develop online course modules and self-directed learning resources aligned with the Essential Principles of Climate Science. Following a national needs assessment survey and a face to face workshop to pilot test topics, a suite of online modules is being developed suitable for self-directed learning by secondary science teachers. Modules are designed around concepts and topics in which teachers express the most interest and need for instruction. Module design also includes attention to effective teaching strategies, such as awareness of student misconceptions, strategies for forestalling controversy and advice from master teachers on implementation and curriculum development. The resources are being developed in partnership with GLOBE, and the National Science Digital Library (NSDL) and is informed by the work of the Climate Literacy and Energy Awareness Network (CLEAN) project. ICEE will help to meet the professional development needs of teachers, including those participating in the GLOBE Student Climate Research Campaign. Modules and self-directed learning resources will be developed and disseminated in partnership with the National Science Digital Library (NSDL). This presentation introduces the needs assessment and pilot workshop data upon which the modules are based, and describes the modules that are available and in development.

Polyubiquitination events mediate polymethylmethacrylate (PMMA) particle activation of NF-kappaB pathway.

PubMed

Yamanaka, Yasuhiro; Karuppaiah, Kannan; Abu-Amer, Yousef

2011-07-08

The pathologic response to implant wear-debris constitutes a major component of inflammatory osteolysis and remains under intense investigation. Polymethylmethacrylate (PMMA) particles, which are released during implant wear and loosening, constitute a major culprit by virtue of inducing inflammatory and osteolytic responses by macrophages and osteoclasts, respectively. Recent work by several groups has identified important cellular entities and secreted factors that contribute to inflammatory osteolysis. In previous work, we have shown that PMMA particles contribute to inflammatory osteolysis through stimulation of major pathways in monocytes/macrophages, primarily NF-κB and MAP kinases. The former pathway requires assembly of large IKK complex encompassing IKK1, IKK2, and IKKγ/NEMO. We have shown recently that interfering with the NF-κB and MAPK activation pathways, through introduction of inhibitors and decoy molecules, impedes PMMA-induced inflammation and osteolysis in mouse models of experimental calvarial osteolysis and inflammatory arthritis. In this study, we report that PMMA particles activate the upstream transforming growth factor β-activated kinase-1 (TAK1), which is a key regulator of signal transduction cascades leading to activation of NF-κB and AP-1 factors. More importantly, we found that PMMA particles induce TAK1 binding to NEMO and UBC13. In addition, we show that PMMA particles induce TRAF6 and UBC13 binding to NEMO and that lack of TRAF6 significantly attenuates NEMO ubiquitination. Altogether, these observations suggest that PMMA particles induce ubiquitination of NEMO, an event likely mediated by TRAF6, TAK1, and UBC13. Our findings provide important information for better understanding of the mechanisms underlying PMMA particle-induced inflammatory responses.

The neuropeptide tachykinin is essential for pheromone detection in a gustatory neural circuit

PubMed Central

Shankar, Shruti; Chua, Jia Yi; Tan, Kah Junn; Calvert, Meredith EK; Weng, Ruifen; Ng, Wan Chin; Mori, Kenji; Yew, Joanne Y

2015-01-01

Gustatory pheromones play an essential role in shaping the behavior of many organisms. However, little is known about the processing of taste pheromones in higher order brain centers. Here, we describe a male-specific gustatory circuit in Drosophila that underlies the detection of the anti-aphrodisiac pheromone (3R,11Z,19Z)-3-acetoxy-11,19-octacosadien-1-ol (CH503). Using behavioral analysis, genetic manipulation, and live calcium imaging, we show that Gr68a-expressing neurons on the forelegs of male flies exhibit a sexually dimorphic physiological response to the pheromone and relay information to the central brain via peptidergic neurons. The release of tachykinin from 8 to 10 cells within the subesophageal zone is required for the pheromone-triggered courtship suppression. Taken together, this work describes a neuropeptide-modulated central brain circuit that underlies the programmed behavioral response to a gustatory sex pheromone. These results will allow further examination of the molecular basis by which innate behaviors are modulated by gustatory cues and physiological state. DOI: http://dx.doi.org/10.7554/eLife.06914.001 PMID:26083710

Flexible packaging for PV modules

NASA Astrophysics Data System (ADS)

Dhere, Neelkanth G.

2008-08-01

Economic, flexible packages that provide needed level of protection to organic and some other PV cells over >25-years have not yet been developed. However, flexible packaging is essential in niche large-scale applications. Typical configuration used in flexible photovoltaic (PV) module packaging is transparent frontsheet/encapsulant/PV cells/flexible substrate. Besides flexibility of various components, the solder bonds should also be flexible and resistant to fatigue due to cyclic loading. Flexible front sheets should provide optical transparency, mechanical protection, scratch resistance, dielectric isolation, water resistance, UV stability and adhesion to encapsulant. Examples are Tefzel, Tedlar and Silicone. Dirt can get embedded in soft layers such as silicone and obscure light. Water vapor transmittance rate (WVTR) of polymer films used in the food packaging industry as moisture barriers are ~0.05 g/(m2.day) under ambient conditions. In comparison, light emitting diodes employ packaging components that have WVTR of ~10-6 g/(m2.day). WVTR of polymer sheets can be improved by coating them with dense inorganic/organic multilayers. Ethylene vinyl acetate, an amorphous copolymer used predominantly by the PV industry has very high O2 and H2O diffusivity. Quaternary carbon chains (such as acetate) in a polymer lead to cleavage and loss of adhesional strength at relatively low exposures. Reactivity of PV module components increases in presence of O2 and H2O. Adhesional strength degrades due to the breakdown of structure of polymer by reactive, free radicals formed by high-energy radiation. Free radical formation in polymers is reduced when the aromatic rings are attached at regular intervals. This paper will review flexible packaging for PV modules.

Photovoltaic module and interlocked stack of photovoltaic modules

DOEpatents

Wares, Brian S.

2012-09-04

One embodiment relates to an arrangement of photovoltaic modules configured for transportation. The arrangement includes a plurality of photovoltaic modules, each photovoltaic module including a frame having at least a top member and a bottom member. A plurality of alignment features are included on the top member of each frame, and a plurality of alignment features are included on the bottom member of each frame. Adjacent photovoltaic modules are interlocked by the alignment features on the top member of a lower module fitting together with the alignment features on the bottom member of an upper module. Other embodiments, features and aspects are also disclosed.

Light Controlled Modulation of Gene Expression by Chemical Optoepigenetic Probes

PubMed Central

Reis, Surya A.; Ghosh, Balaram; Hendricks, J. Adam; Szantai-Kis, D. Miklos; Törk, Lisa; Ross, Kenneth N.; Lamb, Justin; Read-Button, Willis; Zheng, Baixue; Wang, Hongtao; Salthouse, Christopher; Haggarty, Stephen J.; Mazitschek, Ralph

2016-01-01

Epigenetic gene regulation is a dynamic process orchestrated by chromatin-modifying enzymes. Many of these master regulators exert their function through covalent modification of DNA and histone proteins. Aberrant epigenetic processes have been implicated in the pathophysiology of multiple human diseases. Small-molecule inhibitors have been essential to advancing our understanding of the underlying molecular mechanisms of epigenetic processes. However, the resolution offered by small molecules is often insufficient to manipulate epigenetic processes with high spatio-temporal control. Here, we present a novel and generalizable approach, referred to as ‘Chemo-Optical Modulation of Epigenetically-regulated Transcription’ (COMET), enabling high-resolution, optical control of epigenetic mechanisms based on photochromic inhibitors of human histone deacetylases using visible light. COMET probes may translate into novel therapeutic strategies for diseases where conditional and selective epigenome modulation is required. PMID:26974814

Intrinsic signature of essential tremor in the cerebello-frontal network

PubMed Central

Popa, Traian; García-Lorenzo, Daniel; Valabregue, Romain; Legrand, André-Pierre; Marais, Lea; Degos, Bertrand; Hubsch, Cecile; Fernández-Vidal, Sara; Bardinet, Eric; Roze, Emmanuel; Lehéricy, Stéphane; Vidailhet, Marie; Meunier, Sabine

2015-01-01

See Raethjen and Muthuraman (doi:10.1093/brain/awv238) for a scientific commentary on this article. Essential tremor is a movement disorder characterized by tremor during voluntary movements, mainly affecting the upper limbs. The cerebellum and its connections to the cortex are known to be involved in essential tremor, but no task-free intrinsic signatures of tremor related to structural cerebellar defects have so far been found in the cortical motor network. Here we used voxel-based morphometry, tractography and resting-state functional MRI at 3 T to compare structural and functional features in 19 patients with essential tremor and homogeneous symptoms in the upper limbs, and 19 age- and gender-matched healthy volunteers. Both structural and functional abnormalities were found in the patients' cerebellum and supplementary motor area. Relative to the healthy controls, the essential tremor patients' cerebellum exhibited less grey matter in lobule VIII and less effective connectivity between each cerebellar cortex and the ipsilateral dentate nucleus. The patient's supplementary motor area exhibited (i) more grey matter; (ii) a lower amplitude of low-frequency fluctuation of the blood oxygenation level-dependent signal; (iii) less effective connectivity between each supplementary motor area and the ipsilateral primary motor hand area, and (iv) a higher probability of connection between supplementary motor area fibres and the spinal cord. Structural and functional changes in the supplementary motor area, but not in the cerebellum, correlated with clinical severity. In addition, changes in the cerebellum and supplementary motor area were interrelated, as shown by a correlation between the lower amplitude of low-frequency fluctuation in the supplementary motor area and grey matter loss in the cerebellum. The structural and functional changes observed in the supplementary motor area might thus be a direct consequence of cerebellar defects: the supplementary motor area

Experiment module concepts study. Volume 3: Module and subsystem design

NASA Technical Reports Server (NTRS)

Hunter, J. R.; Chiarappa, D. J.

1970-01-01

The final common module set exhibiting wide commonality is described. The set consists of three types of modules: one free flying module and two modules that operate attached to the space station. The common module designs provide for the experiment program as defined. The feasibility, economy, and practicality of these modules hinges on factors that do not affect the approach or results of the commonality process, but are important to the validity of the common module concepts. Implementation of the total experiment program requires thirteen common modules: five CM-1, five CM-3, and three CM-4 modules.

NEMO Binding Domain peptide inhibits constitutive NF-κB activity and reduces tumor burden in a canine model of relapsed, refractory Diffuse Large B-Cell Lymphoma

PubMed Central

Gaurnier-Hausser, Anita; Patel, Reema; Baldwin, Albert S.; May, Michael J.; Mason, Nicola J.

2011-01-01

Purpose Activated B-Cell Diffuse Large B-Cell Lymphoma (ABC-DLBCL) is an aggressive, poorly chemoresponsive lymphoid malignancy characterized by constitutive canonical NF-κB activity that promotes lymphomagenesis and chemotherapy resistance via over-expression of anti-apoptotic NF-κB target genes. Inhibition of the canonical NF-κB pathway may therefore have therapeutic relevance in ABC-DLBCL. Here we set out to determine whether dogs with spontaneous DLBCL have comparative aberrant constitutive NF-κB activity and to determine the therapeutic relevance of NF-κB inhibition in dogs with relapsed, resistant DLBCL. Experimental Design Canonical NF-κB activity was evaluated by electrophoretic mobility shift assays and immunoblot analyses, and NF-κB target gene expression was measured by qRT-PCR. Primary malignant canine B lymphocytes were treated with the selective IKK complex inhibitor Nemo Binding Domain (NBD) peptide, and evaluated for NF-κB activity and apoptosis. NBD peptide was administered intra-nodally to dogs with relapsed B-cell lymphoma and NF-κB target gene expression and tumor burden were evaluated pre and post treatment. Results Constitutive canonical NF-κB activity and increased NF-κB target gene expression was detected in primary DLBCL tissue. NBD peptide inhibited this activity and induced apoptosis of primary malignant B cells in vitro. Intra-tumoral injections of NBD peptide to dogs with relapsed DLBCL inhibited NF-κB target gene expression and reduced tumor burden. Conclusions This work shows that dogs with spontaneous DLBCL represent a clinically relevant, spontaneous, large animal model for human ABC-DLBCL and demonstrates the therapeutic relevance of NF-κB inhibition in the treatment of ABC-DLBCL. These results have important translational relevance for ABC-DLBCL treatment in human patients. PMID:21610150

De Novo Sequencing and Analysis of Lemongrass Transcriptome Provide First Insights into the Essential Oil Biosynthesis of Aromatic Grasses.

PubMed

Meena, Seema; Kumar, Sarma R; Venkata Rao, D K; Dwivedi, Varun; Shilpashree, H B; Rastogi, Shubhra; Shasany, Ajit K; Nagegowda, Dinesh A

2016-01-01

Aromatic grasses of the genus Cymbopogon (Poaceae family) represent unique group of plants that produce diverse composition of monoterpene rich essential oils, which have great value in flavor, fragrance, cosmetic, and aromatherapy industries. Despite the commercial importance of these natural aromatic oils, their biosynthesis at the molecular level remains unexplored. As the first step toward understanding the essential oil biosynthesis, we performed de novo transcriptome assembly and analysis of C. flexuosus (lemongrass) by employing Illumina sequencing. Mining of transcriptome data and subsequent phylogenetic analysis led to identification of terpene synthases, pyrophosphatases, alcohol dehydrogenases, aldo-keto reductases, carotenoid cleavage dioxygenases, alcohol acetyltransferases, and aldehyde dehydrogenases, which are potentially involved in essential oil biosynthesis. Comparative essential oil profiling and mRNA expression analysis in three Cymbopogon species (C. flexuosus, aldehyde type; C. martinii, alcohol type; and C. winterianus, intermediate type) with varying essential oil composition indicated the involvement of identified candidate genes in the formation of alcohols, aldehydes, and acetates. Molecular modeling and docking further supported the role of identified protein sequences in aroma formation in Cymbopogon. Also, simple sequence repeats were found in the transcriptome with many linked to terpene pathway genes including the genes potentially involved in aroma biosynthesis. This work provides the first insights into the essential oil biosynthesis of aromatic grasses, and the identified candidate genes and markers can be a great resource for biotechnological and molecular breeding approaches to modulate the essential oil composition.

De Novo Sequencing and Analysis of Lemongrass Transcriptome Provide First Insights into the Essential Oil Biosynthesis of Aromatic Grasses

PubMed Central

Meena, Seema; Kumar, Sarma R.; Venkata Rao, D. K.; Dwivedi, Varun; Shilpashree, H. B.; Rastogi, Shubhra; Shasany, Ajit K.; Nagegowda, Dinesh A.

2016-01-01

Aromatic grasses of the genus Cymbopogon (Poaceae family) represent unique group of plants that produce diverse composition of monoterpene rich essential oils, which have great value in flavor, fragrance, cosmetic, and aromatherapy industries. Despite the commercial importance of these natural aromatic oils, their biosynthesis at the molecular level remains unexplored. As the first step toward understanding the essential oil biosynthesis, we performed de novo transcriptome assembly and analysis of C. flexuosus (lemongrass) by employing Illumina sequencing. Mining of transcriptome data and subsequent phylogenetic analysis led to identification of terpene synthases, pyrophosphatases, alcohol dehydrogenases, aldo-keto reductases, carotenoid cleavage dioxygenases, alcohol acetyltransferases, and aldehyde dehydrogenases, which are potentially involved in essential oil biosynthesis. Comparative essential oil profiling and mRNA expression analysis in three Cymbopogon species (C. flexuosus, aldehyde type; C. martinii, alcohol type; and C. winterianus, intermediate type) with varying essential oil composition indicated the involvement of identified candidate genes in the formation of alcohols, aldehydes, and acetates. Molecular modeling and docking further supported the role of identified protein sequences in aroma formation in Cymbopogon. Also, simple sequence repeats were found in the transcriptome with many linked to terpene pathway genes including the genes potentially involved in aroma biosynthesis. This work provides the first insights into the essential oil biosynthesis of aromatic grasses, and the identified candidate genes and markers can be a great resource for biotechnological and molecular breeding approaches to modulate the essential oil composition. PMID:27516768

A Comparison between Two Heterodyne Light Sources Using Different Electro-Optic Modulators for Optical Temperature Measurements at Visible Wavelengths

PubMed Central

Twu, Ruey-Ching; Lee, Yi-Huan; Hou, Hong-Yao

2010-01-01

In this paper we have successfully demonstrated a z-propagating Zn-indiffused lithium niobate electro-optic modulator used for optical heterodyne interferometry. Compared to a commercial buck-type electro-optic modulator, the proposed waveguide-type modulator has a lower driving voltage and smaller phase variation while measuring visible wavelengths of 532 nm and 632.8 nm. We also demonstrate an optical temperature measurement system using a homemade modulator. The results show that the measurement sensitivities are almost the same values of 25 deg/°C for both the homemade and the buck-type modulators for a sensing light with a wavelength of 632.8 nm. Because photorefractive impacts are essential in the buck-type modulator at a wavelength of 532 nm, it is difficult to obtain reliable phase measurements, whereas the stable phase operation of the homemade one allows the measurement sensitivity to be improved up to 30 deg/°C with the best measurement resolution at about 0.07 °C for 532 nm. PMID:22163429

ANTIGENIC MODULATION

PubMed Central

Old, Lloyd J.; Stockert, Elisabeth; Boyse, Edward A.; Kim, Jae Ho

1968-01-01

Antigenic modulation (the loss of TL antigens from TL+ cells exposed to TL antibody in the absence of lytic complement) has been demonstrated in vitro. An ascites leukemia, phenotype TL.1,2,3, which modulates rapidly and completely when incubated with TL antiserum in vitro, was selected for further study of the phenomenon. Over a wide range of TL antibody concentrations modulation at 37°C was detectable within 10 min and was complete within approximately 1 hr. The cells were initially sensitized to C' by their contact with antibody, thereafter losing this sensitivity to C' lysis together with their sensitivity to TL antibody and C' in the cytotoxic test. The capacity of the cells to undergo modulation was abolished by actinomycin D and by iodoacetamide, and by reducing the temperature of incubation to 0°C. Thus modulation apparently is an active cellular process. Antigens TL. 1,2, and 3 are all modulated by anti-TL.1,3 serum and by anti-TL.3 serum. This modulation affects all three TL components together, even when antibody to one or two of them is lacking. aAnti-TL.2 serum does not induce modulation and in fact impairs modulation by the other TL antibodies. The influence of the TL phenotype of cells upon the demonstrable content of H-2 (D region) isoantigen, first shown in cells modulated in vivo, has been observed with cells modulated in vitro. Cells undergoing modulation show a progressive increase in H-2 (D region) antigen over a period of 4 hr, with no change in H-2 antigens of the K region. Restoration of the TL+ phenotype of modulated cells after removal of antibody is less rapid than TL+ → TL- modulation and may require several cell divisions. PMID:5636556

Module Configuration

DOEpatents

Oweis, Salah; D'Ussel, Louis; Chagnon, Guy; Zuhowski, Michael; Sack, Tim; Laucournet, Gaullume; Jackson, Edward J.

2002-06-04

A stand alone battery module including: (a) a mechanical configuration; (b) a thermal management configuration; (c) an electrical connection configuration; and (d) an electronics configuration. Such a module is fully interchangeable in a battery pack assembly, mechanically, from the thermal management point of view, and electrically. With the same hardware, the module can accommodate different cell sizes and, therefore, can easily have different capacities. The module structure is designed to accommodate the electronics monitoring, protection, and printed wiring assembly boards (PWAs), as well as to allow airflow through the module. A plurality of modules may easily be connected together to form a battery pack. The parts of the module are designed to facilitate their manufacture and assembly.

Essential Medicines: An Indian Perspective

PubMed Central

Maiti, Rituparna; Bhatia, Vikas; Padhy, Biswa Mohan; Hota, Debasish

2015-01-01

The concept of defining essential medicines and establishing a list of them was aimed to improve the availability of affordable medicines for the world's poor. Access to essential medicines is a major determinant of health outcomes. Several countries have made substantial progress towards increasing access to essential medicines, but access to essential medicines in developing countries like India is not adequate. In this review we have tried to present the Indian scenario in respect to availability and accessibility of essential medicines over last one decade. To enhance the credibility of Indian healthcare system, procurement and delivery systems of essential medicines have to be strengthened through government commitment, careful selection, adequate public sector financing, efficient distribution systems, control on taxes and duties, and inculcating a culture of rational use of medicines in current and future prescribers. PMID:26435594

Paraeducator Professional Development Curriculum. Module III: Assisting the Teacher in the Instruction of Reading. Trainer's Manual

ERIC Educational Resources Information Center

Northwest Regional Educational Laboratory NWREL, 2005

2005-01-01

This two-day institute examines essential concepts about effective teaching strategies in reading, including the five basic components of reading recommended by the National Reading Panel, to enable paraeducators to support teachers in the instruction of reading. The purpose of Module III is to develop participants' understandings of the key…

Modulation of Gamma-Secretase for the Treatment of Alzheimer's Disease

PubMed Central

McKee, Timothy D.; Loureiro, Robyn M. B.; Dumin, Jo Ann; Xia, Weiming; Pojasek, Kevin; Austin, Wesley F.; Fuller, Nathan O.; Hubbs, Jed L.; Shen, Ruichao; Jonker, Jeff; Ives, Jeff; Bronk, Brian S.

2012-01-01

The Amyloid Hypothesis states that the cascade of events associated with Alzheimer's disease (AD)—formation of amyloid plaques, neurofibrillary tangles, synaptic loss, neurodegeneration, and cognitive decline—are triggered by Aβ peptide dysregulation (Kakuda et al., 2006, Sato et al., 2003, Qi-Takahara et al., 2005). Since γ-secretase is critical for Aβ production, many in the biopharmaceutical community focused on γ-secretase as a target for therapeutic approaches for Alzheimer's disease. However, pharmacological approaches to control γ-secretase activity are challenging because the enzyme has multiple, physiologically critical protein substrates. To lower amyloidogenic Aβ peptides without affecting other γ-secretase substrates, the epsilon (ε) cleavage that is essential for the activity of many substrates must be preserved. Small molecule modulators of γ-secretase activity have been discovered that spare the ε cleavage of APP and other substrates while decreasing the production of Aβ 42. Multiple chemical classes of γ-secretase modulators have been identified which differ in the pattern of Aβ peptides produced. Ideally, modulators will allow the ε cleavage of all substrates while shifting APP cleavage from Aβ 42 and other highly amyloidogenic Aβ peptides to shorter and less neurotoxic forms of the peptides without altering the total Aβ pool. Here, we compare chemically distinct modulators for effects on APP processing and in vivo activity. PMID:23320246

Essential Medicines in a High Income Country: Essential to Whom?

PubMed

Duong, Mai; Moles, Rebekah J; Chaar, Betty; Chen, Timothy F

2015-01-01

To explore the perspectives of a diverse group of stakeholders engaged in medicines decision making around what constitutes an "essential" medicine, and how the Essential Medicines List (EML) concept functions in a high income country context. In-depth qualitative semi-structured interviews were conducted with 32 Australian stakeholders, recognised as decision makers, leaders or advisors in the area of medicines reimbursement or supply chain management. Participants were recruited from government, pharmaceutical industry, pharmaceutical wholesale/distribution companies, medicines non-profit organisations, academic health disciplines, hospitals, and consumer groups. Perspectives on the definition and application of the EML concept in a high income country context were thematically analysed using grounded theory approach. Stakeholders found it challenging to describe the EML concept in the Australian context because many perceived it was generally used in resource scarce settings. Stakeholders were unable to distinguish whether nationally reimbursed medicines were essential medicines in Australia. Despite frequent generic drug shortages and high prices paid by consumers, many struggled to describe how the EML concept applied to Australia. Instead, broad inclusion of consumer needs, such as rare and high cost medicines, and consumer involvement in the decision making process, has led to expansive lists of nationally subsidised medicines. Therefore, improved communication and coordination is needed around shared interests between stakeholders regarding how medicines are prioritised and guaranteed in the supply chain. This study showed that decision-making in Australia around reimbursement of medicines has strayed from the fundamental utilitarian concept of essential medicines. Many stakeholders involved in medicine reimbursement decisions and management of the supply chain did not consider the EML concept in their approach. The wide range of views of what stakeholders

Modulation indices for volumetric modulated arc therapy.

PubMed

Park, Jong Min; Park, So-Yeon; Kim, Hyoungnyoun; Kim, Jin Ho; Carlson, Joel; Ye, Sung-Joon

2014-12-07

The aim of this study is to present a modulation index (MI) for volumetric modulated arc therapy (VMAT) based on the speed and acceleration analysis of modulating-parameters such as multi-leaf collimator (MLC) movements, gantry rotation and dose-rate, comprehensively. The performance of the presented MI (MIt) was evaluated with correlation analyses to the pre-treatment quality assurance (QA) results, differences in modulating-parameters between VMAT plans versus dynamic log files, and differences in dose-volumetric parameters between VMAT plans versus reconstructed plans using dynamic log files. For comparison, the same correlation analyses were performed for the previously suggested modulation complexity score (MCS(v)), leaf travel modulation complexity score (LTMCS) and MI by Li and Xing (MI Li&Xing). In the two-tailed unpaired parameter condition, p values were acquired. The Spearman's rho (r(s)) values of MIt, MCSv, LTMCS and MI Li&Xing to the local gamma passing rate with 2%/2 mm criterion were -0.658 (p < 0.001), 0.186 (p = 0.251), 0.312 (p = 0.05) and -0.455 (p = 0.003), respectively. The values of rs to the modulating-parameter (MLC positions) differences were 0.917, -0.635, -0.857 and 0.795, respectively (p < 0.001). For dose-volumetric parameters, MIt showed higher statistically significant correlations than the conventional MIs. The MIt showed good performance for the evaluation of the modulation-degree of VMAT plans.

Essential and non-essential elements in natural vegetation in southern Norway: contribution from different sources.

PubMed

Nordløkken, Marit; Berg, Torunn; Flaten, Trond Peder; Steinnes, Eiliv

2015-01-01

Concentrations of essential and non-essential elements in five widespread species of natural boreal vegetation were studied with respect to seasonal variation and contribution from different sources. The plant species included in the study were Betula pubescens, Sorbus aucuparia, Vaccinium myrtillus, Vaccinium uliginosum, Calluna vulgaris and Deschampsia flexuosa. Concentrations of elements essential to plants remained essentially constant or decreased slightly throughout the growing season. Concentrations of most non-essential elements increased or tended to increase on a dry mass basis from June to July as well as from July to September. The increasing trend for these elements was observed for all species except C. vulgaris. Principal component analysis (PCA) of the material indicated a common source for many of the non-essential elements; Sc, Ti, V, Ga, As, Y, Sb, lanthanides, Pb, Bi, and U, i.e. both elements presumably of geogenic origin and elements associated with trans-boundary air pollution. Uptake by plant roots appeared to be the main source of nutrient elements as well as some non-essential elements. Copyright © 2014 Elsevier B.V. All rights reserved.

Pre-irradiation testing of actively cooled Be-Cu divertor modules

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

Linke, J.; Duwe, R.; Kuehnlein, W.

1995-09-01

A set of neutron irradiation tests is prepared on different plasma facing materials (PFM) candidates and miniaturized components for ITER. Beside beryllium the irradiation program which will be performed in the High Flux Reactor (HFR) in Petten, includes different carbon fiber composites (CFQ) and tungsten alloys. The target values for the neutron irradiation will be 0.5 dpa at temperatures of 350{degrees}C and 700{degrees}C, resp.. The post irradiation examination (PIE) will cover a wide range of mechanical tests; in addition the degradation of thermal conductivity will be investigated. To determine the high heat flux (HHF) performance of actively cooled divertor modules,more » electron beam tests which simulate the expected heat loads during the operation of ITER, are scheduled in the hot cell electron beam facility JUDITH. These tests on a selection of different actively cooled beryllium-copper and CFC-copper divertor modules are performed before and after neutron irradiation; the pre-irradiation testing is an essential part of the program to quantify the zero-fluence high heat flux performance and to detect defects in the modules, in particular in the brazed joints.« less

Rhetoric and Essentially Contested Arguments

ERIC Educational Resources Information Center

Garver, Eugene

1978-01-01

Draws a connection between Gallie's essentially contested concepts and Aristotle's account of rhetorical argument by presenting a definition of Essentially Contested Argument which is used as the connecting term between rhetoric and essentially contested concepts and by demonstrating the value of making this connection. (JF)

LUBAC Formation Is Impaired in the Livers of Mice with MCD-Dependent Nonalcoholic Steatohepatitis.

PubMed

Matsunaga, Yasuka; Nakatsu, Yusuke; Fukushima, Toshiaki; Okubo, Hirofumi; Iwashita, Misaki; Sakoda, Hideyuki; Fujishiro, Midori; Yamamotoya, Takeshi; Kushiyama, Akifumi; Takahashi, Shin-Ichiro; Tsuchiya, Yoshihiro; Kamata, Hideaki; Tokunaga, Fuminori; Iwai, Kazuhiro; Asano, Tomoichiro

2015-01-01

Nonalcoholic steatohepatitis (NASH) is a disorder characterized by hepatic lipid accumulation followed by the inflammation-induced death of hepatocytes and fibrosis. In this process, oxidative stress contributes to the induction of several inflammatory cytokines including TNF-α andIL-1β in macrophages, while, in hepatocytes, NF-κB reportedly induces the expressions of cell survival genes for protection from apoptosis. Recently, it was reported that the new ubiquitin ligase complex termed linear ubiquitin chain assembly complex (LUBAC), composed of SHARPIN (SHANK-associated RH domain-interacting protein), HOIL-1L (longer isoform of heme-oxidized iron-regulatory protein 2 ubiquitin ligase-1), and HOIP (HOIL-1L interacting protein), forms linear ubiquitin on NF-κB essential modulator (NEMO) and thereby induces NF-κB pathway activation. In this study, we demonstrated the formation of LUBAC to be impaired in the livers of NASH rodent models produced by methionine and choline deficient (MCD) diet feeding, first by either gel filtration or Blue Native-PAGE, with subsequent confirmation by western blotting. The reduction of LUBAC is likely to be attributable to markedly reduced expression of SHARPIN, one of its components. Thus, impaired LUBAC formation, which would result in insufficient NF-κB activation, may be one of the molecular mechanisms underlying the enhanced apoptotic response of hepatocytes in MCD diet-induced NASH livers.

Discovery of essential fatty acids

PubMed Central

Spector, Arthur A.; Kim, Hee-Yong

2015-01-01

Dietary fat was recognized as a good source of energy and fat-soluble vitamins by the first part of the 20th century, but fatty acids were not considered to be essential nutrients because they could be synthesized from dietary carbohydrate. This well-established view was challenged in 1929 by George and Mildred Burr who reported that dietary fatty acid was required to prevent a deficiency disease that occurred in rats fed a fat-free diet. They concluded that fatty acids were essential nutrients and showed that linoleic acid prevented the disease and is an essential fatty acid. The Burrs surmised that other unsaturated fatty acids were essential and subsequently demonstrated that linolenic acid, the omega-3 fatty acid analog of linoleic acid, is also an essential fatty acid. The discovery of essential fatty acids was a paradigm-changing finding, and it is now considered to be one of the landmark discoveries in lipid research. PMID:25339684

Mind bomb-1 is an essential modulator of long-term memory and synaptic plasticity via the Notch signaling pathway

PubMed Central

2012-01-01

Background Notch signaling is well recognized as a key regulator of the neuronal fate during embryonic development, but its function in the adult brain is still largely unknown. Mind bomb-1 (Mib1) is an essential positive regulator in the Notch pathway, acting non-autonomously in the signal-sending cells. Therefore, genetic ablation of Mib1 in mature neuron would give valuable insight to understand the cell-to-cell interaction between neurons via Notch signaling for their proper function. Results Here we show that the inactivation of Mib1 in mature neurons in forebrain results in impaired hippocampal dependent spatial memory and contextual fear memory. Consistently, hippocampal slices from Mib1-deficient mice show impaired late-phase, but not early-phase, long-term potentiation and long-term depression without change in basal synaptic transmission at SC-CA1 synapses. Conclusions These data suggest that Mib1-mediated Notch signaling is essential for long-lasting synaptic plasticity and memory formation in the rodent hippocampus. PMID:23111145

Differential network analysis reveals the genome-wide landscape of estrogen receptor modulation in hormonal cancers

PubMed Central

Hsiao, Tzu-Hung; Chiu, Yu-Chiao; Hsu, Pei-Yin; Lu, Tzu-Pin; Lai, Liang-Chuan; Tsai, Mong-Hsun; Huang, Tim H.-M.; Chuang, Eric Y.; Chen, Yidong

2016-01-01

Several mutual information (MI)-based algorithms have been developed to identify dynamic gene-gene and function-function interactions governed by key modulators (genes, proteins, etc.). Due to intensive computation, however, these methods rely heavily on prior knowledge and are limited in genome-wide analysis. We present the modulated gene/gene set interaction (MAGIC) analysis to systematically identify genome-wide modulation of interaction networks. Based on a novel statistical test employing conjugate Fisher transformations of correlation coefficients, MAGIC features fast computation and adaption to variations of clinical cohorts. In simulated datasets MAGIC achieved greatly improved computation efficiency and overall superior performance than the MI-based method. We applied MAGIC to construct the estrogen receptor (ER) modulated gene and gene set (representing biological function) interaction networks in breast cancer. Several novel interaction hubs and functional interactions were discovered. ER+ dependent interaction between TGFβ and NFκB was further shown to be associated with patient survival. The findings were verified in independent datasets. Using MAGIC, we also assessed the essential roles of ER modulation in another hormonal cancer, ovarian cancer. Overall, MAGIC is a systematic framework for comprehensively identifying and constructing the modulated interaction networks in a whole-genome landscape. MATLAB implementation of MAGIC is available for academic uses at https://github.com/chiuyc/MAGIC. PMID:26972162

Cross-Modulation Interference with Lateralization of Mixed-Modulated Waveforms

ERIC Educational Resources Information Center

Hsieh, I-Hui; Petrosyan, Agavni; Goncalves, Oscar F.; Hickok, Gregory; Saberi, Kourosh

2010-01-01

Purpose: This study investigated the ability to use spatial information in mixed-modulated (MM) sounds containing concurrent frequency-modulated (FM) and amplitude-modulated (AM) sounds by exploring patterns of interference when different modulation types originated from different loci as may occur in a multisource acoustic field. Method:…

Experimental study on the thrust modulation performance of powdered magnesium and CO2 bipropellant engine

NASA Astrophysics Data System (ADS)

Li, Chao; Hu, Chunbo; Zhu, Xiaofei; Hu, Jiaming; Li, Yue; Hu, Xu

2018-06-01

Powdered Mg and CO2 bipropellant engine providing a practical demonstration of in situ resource utilization (ISRU) for Mars Sample Return (MSR) mission seems to be feasible by current investigations. However, essential functions of the engine to satisfy the complicated ballistics requirements such as thrust modulation and multiple pulse have not been established yet. The aim of this experimental study is to evaluate the engine's thrust modulation feasibility and to investigate its thrust modulation characteristics. A powdered Mg and CO2 bipropellant engine construction aiming to achieve thrust modulation ability was proposed. A mass flow rate calibration experiment to evaluate the gas-solid mass flow rate regulating performance was conducted before fire tests. Fire test result shows that the engine achieved successful ignition as well as self-sustaining combustion; Thrust modulation of the engine is feasible, detail thrust estimating result of the test shows that maximum thrust is 135.91 N and the minimum is 5.65 N with a 22.11 thrust modulation ratio, moreover, the transportation period is quick and the thrust modulation ratio is adjustable. At the same time, the powder feed system reaches a two-step flow rate regulating with a modulation ratio of 4.5-5. What' more, caused by the uneven engine working conditions, there is an obvious difference in combustion efficiency value, maximum combustion efficiency of the powdered Mg and CO2 bipropellant engine is 80.20%.

Apollo 9 Command/Service Modules photographed from Lunar Module

NASA Technical Reports Server (NTRS)

1969-01-01

The Apollo 9 Command/Service Modules photographed from the Lunar Module, 'Spider', on the fifth day of the Apollo 9 earth-orbital mission. Docking mechanism is visible in nose of the Command Module, 'Gumdrop'. Object jutting out from the Service Module aft bulkhead is the high-gain S-Band antenna.

Toward variational assimilation of SARAL/Altika altimeter data in a North Atlantic circulation model at eddy-permitting resolution: assessment of a NEMO-based 4D-VAR system

NASA Astrophysics Data System (ADS)

Bouttier, Pierre-Antoine; Brankart, Jean-Michel; Candille, Guillem; Vidard, Arthur; Blayo, Eric; Verron, Jacques; Brasseur, Pierre

2015-04-01

In this project, the response of a variational data assimilation system based on NEMO and its linear tangent and adjoint model is investigated using a 4DVAR algorithm into a North-Atlantic model at eddy-permitting resolution. The assimilated data consist of Jason-2 and SARAL/AltiKA dataset collected during the 2013-2014 period. The main objective is to explore the robustness of the 4DVAR algorithm in the context of a realistic turbulent oceanic circulation at mid-latitude constrained by multi-satellite altimetry missions. This work relies on two previous studies. First, a study with similar objectives was performed based on academic double-gyre turbulent model and synthetic SARAL/AltiKA data, using the same DA experimental framework. Its main goal was to investigate the impact of turbulence on variational DA methods performance. The comparison with this previous work will bring to light the methodological and physical issues encountered by variational DA algorithms in a realistic context at similar, eddy-permitting spatial resolution. We also have demonstrated how a dataset mimicking future SWOT observations improves 4DVAR incremental performances at eddy-permitting resolution. Then, in the context of the OSTST and FP7 SANGOMA projects, an ensemble DA experiment based on the same model and observational datasets has been realized (see poster by Brasseur et al.). This work offers the opportunity to compare efficiency, pros and cons of both DA methods in the context of KA-band altimetric data, at spatial resolution commonly used today for research and operational applications. In this poster we will present the validation plan proposed to evaluate the skill of variational experiment vs. ensemble assimilation experiments covering the same period using independent observations (e.g. from Cryosat-2 mission).

High modulation bandwidth of a light-emitting diode with surface plasmon coupling (Conference Presentation)

NASA Astrophysics Data System (ADS)

Lin, Chun-Han; Tu, Charng-Gan; Yao, Yu-Feng; Chen, Sheng-Hung; Su, Chia-Ying; Chen, Hao-Tsung; Kiang, Yean-Woei; Yang, Chih-Chung

2017-02-01

Besides lighting, LEDs can be used for indoor data transmission. Therefore, a large modulation bandwidth becomes an important target in the development of visible LED. In this regard, enhancing the radiative recombination rate of carriers in the quantum wells of an LED is a useful method since the modulation bandwidth of an LED is related to the carrier decay rate besides the device RC time constant To increase the carrier decay rate in an LED without sacrificing its output power, the technique of surface plasmon (SP) coupling in an LED is useful. In this paper, the increases of modulation bandwidth by reducing mesa size, decreasing active layer thickness, and inducing SP coupling in blue- and green-emitting LEDs are illustrated. The results are demonstrated by comparing three different LED surface structures, including bare p-type surface, GaZnO current spreading layer, and Ag nanoparticles (NPs) for inducing SP coupling. In a single-quantum-well, blue-emitting LED with a circular mesa of 10 microns in radius, SP coupling results in a modulation bandwidth of 528.8 MHz, which is believed to be the record-high level. A smaller RC time constant can lead to a higher modulation bandwidth. However, when the RC time constant is smaller than 0.2 ns, its effect on modulation bandwidth saturates. The dependencies of modulation bandwidth on injected current density and carrier decay time confirm that the modulation bandwidth is essentially inversely proportional to a time constant, which is inversely proportional to the square-root of carrier decay rate and injected current density.

Essentialism goes social: belief in social determinism as a component of psychological essentialism.

PubMed

Rangel, Ulrike; Keller, Johannes

2011-06-01

Individuals tend to explain the characteristics of others with reference to an underlying essence, a tendency that has been termed psychological essentialism. Drawing on current conceptualizations of essentialism as a fundamental mode of social thinking, and on prior studies investigating belief in genetic determinism (BGD) as a component of essentialism, we argue that BGD cannot constitute the sole basis of individuals' essentialist reasoning. Accordingly, we propose belief in social determinism (BSD) as a complementary component of essentialism, which relies on the belief that a person's essential character is shaped by social factors (e.g., upbringing, social background). We developed a scale to measure this social component of essentialism. Results of five correlational studies indicate that (a) BGD and BSD are largely independent, (b) BGD and BSD are related to important correlates of essentialist thinking (e.g., dispositionism, perceived group homogeneity), (c) BGD and BSD are associated with indicators of fundamental epistemic and ideological motives, and (d) the endorsement of each lay theory is associated with vital social-cognitive consequences (particularly stereotyping and prejudice). Two experimental studies examined the idea that the relationship between BSD and prejudice is bidirectional in nature. Study 6 reveals that rendering social-deterministic explanations salient results in increased levels of ingroup favoritism in individuals who chronically endorse BSD. Results of Study 7 show that priming of prejudice enhances endorsement of social-deterministic explanations particularly in persons habitually endorsing prejudiced attitudes. 2011 APA, all rights reserved

Evidence that Mediator is essential for Pol II transcription, but is not a required component of the preinitiation complex in vivo.

PubMed

Petrenko, Natalia; Jin, Yi; Wong, Koon Ho; Struhl, Kevin

2017-07-12

The Mediator complex has been described as a general transcription factor, but it is unclear if it is essential for Pol II transcription and/or is a required component of the preinitiation complex (PIC) in vivo. Here, we show that depletion of individual subunits, even those essential for cell growth, causes a general but only modest decrease in transcription. In contrast, simultaneous depletion of all Mediator modules causes a drastic decrease in transcription. Depletion of head or middle subunits, but not tail subunits, causes a downstream shift in the Pol II occupancy profile, suggesting that Mediator at the core promoter inhibits promoter escape. Interestingly, a functional PIC and Pol II transcription can occur when Mediator is not detected at core promoters. These results provide strong evidence that Mediator is essential for Pol II transcription and stimulates PIC formation, but it is not a required component of the PIC in vivo.

Distinct Thalamic Reticular Cell Types Differentially Modulate Normal and Pathological Cortical Rhythms.

PubMed

Clemente-Perez, Alexandra; Makinson, Stefanie Ritter; Higashikubo, Bryan; Brovarney, Scott; Cho, Frances S; Urry, Alexander; Holden, Stephanie S; Wimer, Matthew; Dávid, Csaba; Fenno, Lief E; Acsády, László; Deisseroth, Karl; Paz, Jeanne T

2017-06-06

Integrative brain functions depend on widely distributed, rhythmically coordinated computations. Through its long-ranging connections with cortex and most senses, the thalamus orchestrates the flow of cognitive and sensory information. Essential in this process, the nucleus reticularis thalami (nRT) gates different information streams through its extensive inhibition onto other thalamic nuclei, however, we lack an understanding of how different inhibitory neuron subpopulations in nRT function as gatekeepers. We dissociated the connectivity, physiology, and circuit functions of neurons within rodent nRT, based on parvalbumin (PV) and somatostatin (SOM) expression, and validated the existence of such populations in human nRT. We found that PV, but not SOM, cells are rhythmogenic, and that PV and SOM neurons are connected to and modulate distinct thalamocortical circuits. Notably, PV, but not SOM, neurons modulate somatosensory behavior and disrupt seizures. These results provide a conceptual framework for how nRT may gate incoming information to modulate brain-wide rhythms. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

The colony environment modulates sleep in honey bee workers.

PubMed

Eban-Rothschild, Ada; Bloch, Guy

2015-02-01

One of the most important and evolutionarily conserved roles of sleep is the processing and consolidation of information acquired during wakefulness. In both insects and mammals, environmental and social stimuli can modify sleep physiology and behavior, yet relatively little is known about the specifics of the wake experiences and their relative contribution to experience-dependent modulation of sleep. Honey bees provide an excellent model system in this regard because their behavioral repertoire is well characterized and the environment they experience during the day can be manipulated while keeping an ecologically and sociobiologically relevant context. We examined whether social experience modulates sleep in honey bees, and evaluated the relative contribution of different social signals. We exposed newly emerged bees to different components of their natural social environment and then monitored their sleep behavior in individual cages in a constant lab environment. We found that rich waking experience modulates subsequent sleep. Bees that experienced the colony environment for 1 or 2 days slept more than same-age sister bees that were caged individually or in small groups in the lab. Furthermore, bees placed in mesh-enclosures in the colony, that prevented direct contact with nestmates, slept similarly to bees freely moving in the colony. These results suggest that social signals that do not require direct or close distance interactions between bees are sufficiently rich to encompass almost the entire effect of the colony on sleep. Our findings provide a remarkable example of social experience-dependent modulation of an essential biological process. © 2015. Published by The Company of Biologists Ltd.

Towards the Structure Determination of a Modulated Protein Crystal: The Semicrystalline State of Profilin:Actin

NASA Technical Reports Server (NTRS)

Borgstahl, G.; Lovelace, J.; Snell, E. H.; Bellamy, H.

2003-01-01

One of the remaining challenges to structural biology is the solution of modulated structures. While small molecule crystallographers have championed this type of structure, to date, no modulated macromolecular structures have been determined. Modulation of the molecular structures within the crystal can produce satellite reflections or a superlattice of reflections in reciprocal space. We have developed the data collection methods and strategies that are needed to collect and analyze these data. If the macromolecule's crystal lattice is composed of physiologically relevant packing contacts, structural changes induced under physiological conditions can cause distortion relevant to the function and biophysical processes of the molecule making up the crystal. By careful measurement of the distortion, and the corresponding three-dimensional structure of the distorted molecule, we will visualize the motion and mechanism of the biological macromolecule(s). We have measured the modulated diffraction pattern produced by the semicrystalline state of profilin:actin crystals using highly parallel and highly monochromatic synchrotron radiation coupled with fine phi slicing (0.001-0.010 degrees) for structure determination. These crystals present these crystals present a unique opportunity to address an important question in structural biology. The modulation is believed to be due to the formation of actin helical filaments from the actin beta ribbon upon the pH-induced dissociation of profilin. To date, the filamentous state of actin has resisted crystallization and no detailed structures are available. The semicrystalline state profilin:actin crystals provides a unique opportunity to understand the many conformational states of actin. This knowledge is essential for understanding the dynamics underlying shape changes and motility of eukaryotic cells. Many essential processes, such as cytokinesis, phagocytosis, and cellular migration depend upon the capacity of the actin

Essential Oils and Antifungal Activity

PubMed Central

Coppola, Raffaele; De Feo, Vincenzo

2017-01-01

Since ancient times, folk medicine and agro-food science have benefitted from the use of plant derivatives, such as essential oils, to combat different diseases, as well as to preserve food. In Nature, essential oils play a fundamental role in protecting the plant from biotic and abiotic attacks to which it may be subjected. Many researchers have analyzed in detail the modes of action of essential oils and most of their components. The purpose of this brief review is to describe the properties of essential oils, principally as antifungal agents, and their role in blocking cell communication mechanisms, fungal biofilm formation, and mycotoxin production. PMID:29099084

Modulation of mitochondrial ion transport by inorganic polyphosphate - essential role in mitochondrial permeability transition pore.

PubMed

Baev, Artyom Y; Negoda, Alexander; Abramov, Andrey Y

2017-02-01

Inorganic polyphosphate (polyP) is a biopolymer of phosphoanhydride-linked orthophosphate residues. PolyP is involved in multiple cellular processes including mitochondrial metabolism and cell death. We used artificial membranes and isolated mitochondria to investigate the role of the polyP in mitochondrial ion transport and in activation of PTP. Here, we found that polyP can modify ion permeability of de-energised mitochondrial membranes but not artificial membranes. This permeability was selective for Ba 2+ and Ca 2+ but not for other monovalent and bivalent cations and can be blocked by inhibitors of the permeability transition pore - cyclosporine A or ADP. Lower concentrations of polyP modulate calcium dependent permeability transition pore opening. Increase in polyP concentrations and elongation chain length of the polymer causes calcium independent swelling in energized conditions. Physiologically relevant concentrations of inorganic polyP can regulate calcium dependent as well calcium independent mitochondrial permeability transition pore opening. This raises the possibility that cytoplasmic polyP can be an important contributor towards regulation of the cell death.

The dynamics of integrate-and-fire: mean versus variance modulations and dependence on baseline parameters.

PubMed

Pressley, Joanna; Troyer, Todd W

2011-05-01

The leaky integrate-and-fire (LIF) is the simplest neuron model that captures the essential properties of neuronal signaling. Yet common intuitions are inadequate to explain basic properties of LIF responses to sinusoidal modulations of the input. Here we examine responses to low and moderate frequency modulations of both the mean and variance of the input current and quantify how these responses depend on baseline parameters. Across parameters, responses to modulations in the mean current are low pass, approaching zero in the limit of high frequencies. For very low baseline firing rates, the response cutoff frequency matches that expected from membrane integration. However, the cutoff shows a rapid, supralinear increase with firing rate, with a steeper increase in the case of lower noise. For modulations of the input variance, the gain at high frequency remains finite. Here, we show that the low-frequency responses depend strongly on baseline parameters and derive an analytic condition specifying the parameters at which responses switch from being dominated by low versus high frequencies. Additionally, we show that the resonant responses for variance modulations have properties not expected for common oscillatory resonances: they peak at frequencies higher than the baseline firing rate and persist when oscillatory spiking is disrupted by high noise. Finally, the responses to mean and variance modulations are shown to have a complementary dependence on baseline parameters at higher frequencies, resulting in responses to modulations of Poisson input rates that are independent of baseline input statistics.

Essential thrombocythemia

MedlinePlus

... leukemia (cancer that starts in the bone marrow) Polycythemia vera (bone marrow disease that leads to an ... PA: Elsevier Saunders; 2013:chap 68. Tefferi A. Polycythemia vera, essential thrombocythemia, and primary myelofibrosis. In: Goldman ...

System for Automated Calibration of Vector Modulators

NASA Technical Reports Server (NTRS)

Lux, James; Boas, Amy; Li, Samuel

2009-01-01

correction tables to allow the commanding of the phase shift in each of four channels used as a phased array for beam steering of a Ka-band (32-GHz) signal. The system also was the basis of a breadboard electronic beam steering system. In this breadboard, the goal was not to make systematic measurements of the properties of a vector modulator, but to drive the breadboard with a series of test patterns varying in phase and amplitude. This is essentially the same calibration process, but with the difference that the data collection process is oriented toward collecting breadboard performance, rather than the measurement of output from a network analyzer.

Ultrasensitive detection of atmospheric trace gases using frequency modulation spectroscopy

NASA Technical Reports Server (NTRS)

Cooper, David E.

1986-01-01

Frequency modulation (FM) spectroscopy is a new technique that promises to significantly extend the state-of-the-art in point detection of atmospheric trace gases. FM spectroscopy is essentially a balanced bridge optical heterodyne approach in which a small optical absorption or dispersion from an atomic or molecular species of interest generates an easily detected radio frequency (RF) signal. This signal can be monitored using standard RF signal processing techniques and is, in principle, limited only by the shot noise generated in the photodetector by the laser source employed. The use of very high modulation frequencies which exceed the spectral width of the probed absorption line distinguishes this technique from the well-known derivative spectroscopy which makes use of low (kHz) modulation frequencies. FM spectroscopy was recently extended to the 10 micron infrared (IR) spectral region where numerous polyatomic molecules exhibit characteristic vibrational-rotational bands. In conjunction with tunable semiconductor diode lasers, the quantum-noise-limited sensitivity of the technique should allow for the detection of absorptions as small as .00000001 in the IR spectral region. This sensitivity would allow for the detection of H2O2 at concentrations as low as 1 pptv with an integration time of 10 seconds.

Evidence that Mediator is essential for Pol II transcription, but is not a required component of the preinitiation complex in vivo

PubMed Central

Petrenko, Natalia; Jin, Yi; Wong, Koon Ho; Struhl, Kevin

2017-01-01

The Mediator complex has been described as a general transcription factor, but it is unclear if it is essential for Pol II transcription and/or is a required component of the preinitiation complex (PIC) in vivo. Here, we show that depletion of individual subunits, even those essential for cell growth, causes a general but only modest decrease in transcription. In contrast, simultaneous depletion of all Mediator modules causes a drastic decrease in transcription. Depletion of head or middle subunits, but not tail subunits, causes a downstream shift in the Pol II occupancy profile, suggesting that Mediator at the core promoter inhibits promoter escape. Interestingly, a functional PIC and Pol II transcription can occur when Mediator is not detected at core promoters. These results provide strong evidence that Mediator is essential for Pol II transcription and stimulates PIC formation, but it is not a required component of the PIC in vivo. DOI: http://dx.doi.org/10.7554/eLife.28447.001 PMID:28699889

Improving the human readability of Arden Syntax medical logic modules using a concept-oriented terminology and object-oriented programming expressions.

PubMed

Choi, Jeeyae; Bakken, Suzanne; Lussier, Yves A; Mendonça, Eneida A

2006-01-01

Medical logic modules are a procedural representation for sharing task-specific knowledge for decision support systems. Based on the premise that clinicians may perceive object-oriented expressions as easier to read than procedural rules in Arden Syntax-based medical logic modules, we developed a method for improving the readability of medical logic modules. Two approaches were applied: exploiting the concept-oriented features of the Medical Entities Dictionary and building an executable Java program to replace Arden Syntax procedural expressions. The usability evaluation showed that 66% of participants successfully mapped all Arden Syntax rules to Java methods. These findings suggest that these approaches can play an essential role in the creation of human readable medical logic modules and can potentially increase the number of clinical experts who are able to participate in the creation of medical logic modules. Although our approaches are broadly applicable, we specifically discuss the relevance to concept-oriented nursing terminologies and automated processing of task-specific nursing knowledge.

Electroabsorption optical modulator

DOEpatents

Skogen, Erik J.

2017-11-21

An electroabsorption modulator incorporates waveguiding regions along the length of the modulator that include quantum wells where at least two of the regions have quantum wells with different bandgaps. In one embodiment of the invention, the regions are arranged such that the quantum wells have bandgaps with decreasing bandgap energy along the length of the modulator from the modulator's input to its output. The bandgap energy of the quantum wells may be decreased in discrete steps or continuously. Advantageously, such an arrangement better distributes the optical absorption as well as the carrier density along the length of the modulator. Further advantageously, the modulator may handle increased optical power as compared with prior art modulators of similar dimensions, which allows for improved link gain when the optical modulator is used in an analog optical communication link.

Complex modulation using tandem polarization modulators

NASA Astrophysics Data System (ADS)

Hasan, Mehedi; Hall, Trevor

2017-11-01

A novel photonic technique for implementing frequency up-conversion or complex modulation is proposed. The proposed circuit consists of a sandwich of a quarter-wave plate between two polarization modulators, driven, respectively, by an in-phase and quadrature-phase signals. The operation of the circuit is modelled using a transmission matrix method. The theoretical prediction is then validated by simulation using an industry-standard software tool. The intrinsic conversion efficiency of the architecture is improved by 6 dB over a functionally equivalent design based on dual parallel Mach-Zehnder modulators. Non-ideal scenarios such as imperfect alignment of the optical components and power imbalances and phase errors in the electric drive signals are also analysed. As light travels, along one physical path, the proposed design can be implemented using discrete components with greater control of relative optical path length differences. The circuit can further be integrated in any material platform that offers electro-optic polarization modulators.

Systematic Identification of MCU Modulators by Orthogonal Interspecies Chemical Screening.

PubMed

Arduino, Daniela M; Wettmarshausen, Jennifer; Vais, Horia; Navas-Navarro, Paloma; Cheng, Yiming; Leimpek, Anja; Ma, Zhongming; Delrio-Lorenzo, Alba; Giordano, Andrea; Garcia-Perez, Cecilia; Médard, Guillaume; Kuster, Bernhard; García-Sancho, Javier; Mokranjac, Dejana; Foskett, J Kevin; Alonso, M Teresa; Perocchi, Fabiana

2017-08-17

The mitochondrial calcium uniporter complex is essential for calcium (Ca 2+ ) uptake into mitochondria of all mammalian tissues, where it regulates bioenergetics, cell death, and Ca 2+ signal transduction. Despite its involvement in several human diseases, we currently lack pharmacological agents for targeting uniporter activity. Here we introduce a high-throughput assay that selects for human MCU-specific small-molecule modulators in primary drug screens. Using isolated yeast mitochondria, reconstituted with human MCU, its essential regulator EMRE, and aequorin, and exploiting a D-lactate- and mannitol/sucrose-based bioenergetic shunt that greatly minimizes false-positive hits, we identify mitoxantrone out of more than 600 clinically approved drugs as a direct selective inhibitor of human MCU. We validate mitoxantrone in orthogonal mammalian cell-based assays, demonstrating that our screening approach is an effective and robust tool for MCU-specific drug discovery and, more generally, for the identification of compounds that target mitochondrial functions. Copyright © 2017 Elsevier Inc. All rights reserved.

Essential Oils Modulate Gene Expression and Ochratoxin A Production in Aspergillus carbonarius.

PubMed

El Khoury, Rachelle; Atoui, Ali; Verheecke, Carol; Maroun, Richard; El Khoury, Andre; Mathieu, Florence

2016-08-19

Ochratoxin A (OTA) is a mycotoxin, mainly produced on grapes by Aspergillus carbonarius, that causes massive health problems for humans. This study aims to reduce the occurrence of OTA by using the ten following essential oils (E.Os): fennel, cardamom, anise, chamomile, celery, cinnamon, thyme, taramira, oregano and rosemary at 1 µL/mL and 5 µL/mL for each E.O.As a matter of fact, their effects on the OTA production and the growth of A. carbonarius S402 cultures were evaluated, after four days at 28 °C on a Synthetic Grape Medium (SGM). Results showed that A. carbonarius growth was reduced up to 100%, when cultured with the E.Os of cinnamon, taramira, and oregano at both concentrations and the thyme at 5 µL/mL. As for the other six E.Os, their effect on A. carbonarius growth was insignificant, but highly important on the OTA production. Interestingly, the fennel E.O at 5 µL/mL reduced the OTA production up to 88.9% compared to the control, with only 13.8% of fungal growth reduction. We further investigated the effect of these E.Os on the expression levels of the genes responsible for the OTA biosynthesis (acOTApks and acOTAnrps along with the acpks gene) as well as the two regulatory genes laeA and vea, using the quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) method. The results revealed that these six E.Os reduced the expression of the five studied genes, where the ackps was downregulated by 99.2% (the highest downregulation in this study) with 5 µL/mL of fennel E.O.As for the acOTApks, acOTAnrps, veA and laeA, their reduction levels ranged between 10% and 96% depending on the nature of the E.O and its concentration in the medium.

Supported PV module assembly

DOEpatents

Mascolo, Gianluigi; Taggart, David F.; Botkin, Jonathan D.; Edgett, Christopher S.

2013-10-15

A supported PV assembly may include a PV module comprising a PV panel and PV module supports including module supports having a support surface supporting the module, a module registration member engaging the PV module to properly position the PV module on the module support, and a mounting element. In some embodiments the PV module registration members engage only the external surfaces of the PV modules at the corners. In some embodiments the assembly includes a wind deflector with ballast secured to a least one of the PV module supports and the wind deflector. An array of the assemblies can be secured to one another at their corners to prevent horizontal separation of the adjacent corners while permitting the PV modules to flex relative to one another so to permit the array of PV modules to follow a contour of the support surface.

SSER: Species specific essential reactions database.

PubMed

Labena, Abraham A; Ye, Yuan-Nong; Dong, Chuan; Zhang, Fa-Z; Guo, Feng-Biao

2017-04-19

Essential reactions are vital components of cellular networks. They are the foundations of synthetic biology and are potential candidate targets for antimetabolic drug design. Especially if a single reaction is catalyzed by multiple enzymes, then inhibiting the reaction would be a better option than targeting the enzymes or the corresponding enzyme-encoding gene. The existing databases such as BRENDA, BiGG, KEGG, Bio-models, Biosilico, and many others offer useful and comprehensive information on biochemical reactions. But none of these databases especially focus on essential reactions. Therefore, building a centralized repository for this class of reactions would be of great value. Here, we present a species-specific essential reactions database (SSER). The current version comprises essential biochemical and transport reactions of twenty-six organisms which are identified via flux balance analysis (FBA) combined with manual curation on experimentally validated metabolic network models. Quantitative data on the number of essential reactions, number of the essential reactions associated with their respective enzyme-encoding genes and shared essential reactions across organisms are the main contents of the database. SSER would be a prime source to obtain essential reactions data and related gene and metabolite information and it can significantly facilitate the metabolic network models reconstruction and analysis, and drug target discovery studies. Users can browse, search, compare and download the essential reactions of organisms of their interest through the website http://cefg.uestc.edu.cn/sser .

New extension software modules to enhance searching and display of transcriptome data in Tripal databases

PubMed Central

Chen, Ming; Henry, Nathan; Almsaeed, Abdullah; Zhou, Xiao; Wegrzyn, Jill; Ficklin, Stephen

2017-01-01

Abstract Tripal is an open source software package for developing biological databases with a focus on genetic and genomic data. It consists of a set of core modules that deliver essential functions for loading and displaying data records and associated attributes including organisms, sequence features and genetic markers. Beyond the core modules, community members are encouraged to contribute extension modules to build on the Tripal core and to customize Tripal for individual community needs. To expand the utility of the Tripal software system, particularly for RNASeq data, we developed two new extension modules. Tripal Elasticsearch enables fast, scalable searching of the entire content of a Tripal site as well as the construction of customized advanced searches of specific data types. We demonstrate the use of this module for searching assembled transcripts by functional annotation. A second module, Tripal Analysis Expression, houses and displays records from gene expression assays such as RNA sequencing. This includes biological source materials (biomaterials), gene expression values and protocols used to generate the data. In the case of an RNASeq experiment, this would reflect the individual organisms and tissues used to produce sequencing libraries, the normalized gene expression values derived from the RNASeq data analysis and a description of the software or code used to generate the expression values. The module will load data from common flat file formats including standard NCBI Biosample XML. Data loading, display options and other configurations can be controlled by authorized users in the Drupal administrative backend. Both modules are open source, include usage documentation, and can be found in the Tripal organization’s GitHub repository. Database URL: Tripal Elasticsearch module: https://github.com/tripal/tripal_elasticsearch Tripal Analysis Expression module: https://github.com/tripal/tripal_analysis_expression PMID:29220446

Kinetic modeling of plant metabolism and its predictive power: peppermint essential oil biosynthesis as an example.

PubMed

Lange, Bernd Markus; Rios-Estepa, Rigoberto

2014-01-01

The integration of mathematical modeling with analytical experimentation in an iterative fashion is a powerful approach to advance our understanding of the architecture and regulation of metabolic networks. Ultimately, such knowledge is highly valuable to support efforts aimed at modulating flux through target pathways by molecular breeding and/or metabolic engineering. In this article we describe a kinetic mathematical model of peppermint essential oil biosynthesis, a pathway that has been studied extensively for more than two decades. Modeling assumptions and approximations are described in detail. We provide step-by-step instructions on how to run simulations of dynamic changes in pathway metabolites concentrations.

Processing module operating methods, processing modules, and communications systems

DOEpatents

McCown, Steven Harvey; Derr, Kurt W.; Moore, Troy

2014-09-09

A processing module operating method includes using a processing module physically connected to a wireless communications device, requesting that the wireless communications device retrieve encrypted code from a web site and receiving the encrypted code from the wireless communications device. The wireless communications device is unable to decrypt the encrypted code. The method further includes using the processing module, decrypting the encrypted code, executing the decrypted code, and preventing the wireless communications device from accessing the decrypted code. Another processing module operating method includes using a processing module physically connected to a host device, executing an application within the processing module, allowing the application to exchange user interaction data communicated using a user interface of the host device with the host device, and allowing the application to use the host device as a communications device for exchanging information with a remote device distinct from the host device.

Exploring the benefits of an optional theatre module on medical student well-being.

PubMed

Nagji, Alim; Brett-MacLean, Pamela; Breault, Lorraine

2013-01-01

Medical students struggle with varied stressors and developing adequate coping mechanisms is essential. This study examined medical student perceptions of the well-being impact of a theatre-based course. Eighteen 1st-year medical students at the University of Alberta participated in 3 focus groups following the conclusion of a theatre-based module that was piloted in the first quarter of 2010. A semistructured protocol was used to guide the focus groups, which were audiotaped and transcribed. Along with general feedback, impact on personal development and student well-being were discussed. Thematic aspects of these discussions were qualitatively analyzed. During the focus groups, medical students identified three aspects of the theatre-based module that contributed to their sense of overall well-being. These included (a) fun/relaxation, (b) enhanced relationships with each other, and (c) personal growth/resilience. Our findings suggest that participating in an optional theatre module can enhance medical student well-being. Our analysis suggests the need to consider novel, humanities-based curriculum offerings in relation to personal development and well- being.

Development of an aerosol microphysical module: Aerosol Two-dimensional bin module for foRmation and Aging Simulation (ATRAS)

NASA Astrophysics Data System (ADS)

Matsui, H.; Koike, M.; Kondo, Y.; Fast, J. D.; Takigawa, M.

2014-09-01

Number concentrations, size distributions, and mixing states of aerosols are essential parameters for accurate estimations of aerosol direct and indirect effects. In this study, we develop an aerosol module, designated the Aerosol Two-dimensional bin module for foRmation and Aging Simulation (ATRAS), that can explicitly represent these parameters by considering new particle formation (NPF), black carbon (BC) aging, and secondary organic aerosol (SOA) processes. A two-dimensional bin representation is used for particles with dry diameters from 40 nm to 10 μm to resolve both aerosol sizes (12 bins) and BC mixing states (10 bins) for a total of 120 bins. The particles with diameters between 1 and 40 nm are resolved using additional eight size bins to calculate NPF. The ATRAS module is implemented in the WRF-Chem model and applied to examine the sensitivity of simulated mass, number, size distributions, and optical and radiative parameters of aerosols to NPF, BC aging, and SOA processes over East Asia during the spring of 2009. The BC absorption enhancement by coating materials is about 50% over East Asia during the spring, and the contribution of SOA processes to the absorption enhancement is estimated to be 10-20% over northern East Asia and 20-35% over southern East Asia. A clear north-south contrast is also found between the impacts of NPF and SOA processes on cloud condensation nuclei (CCN) concentrations: NPF increases CCN concentrations at higher supersaturations (smaller particles) over northern East Asia, whereas SOA increases CCN concentrations at lower supersaturations (larger particles) over southern East Asia. The application of ATRAS in East Asia also shows that the impact of each process on each optical and radiative parameter depends strongly on the process and the parameter in question. The module can be used in the future as a benchmark model to evaluate the accuracy of simpler aerosol models and examine interactions between NPF, BC aging, and SOA

Development of an aerosol microphysical module: Aerosol Two-dimensional bin module for foRmation and Aging Simulation (ATRAS)

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

Matsui, H.; Koike, Makoto; Kondo, Yutaka

2014-09-30

Number concentrations, size distributions, and mixing states of aerosols are essential parameters for accurate estimation of aerosol direct and indirect effects. In this study, we developed an aerosol module, designated Aerosol Two-dimensional bin module for foRmation and Aging Simulation (ATRAS), that can represent these parameters explicitly by considering new particle formation (NPF), black carbon (BC) aging, and secondary organic aerosol (SOA) processes. A two-dimensional bin representation is used for particles with dry diameters from 40 nm to 10 µm to resolve both aerosol size (12 bins) and BC mixing state (10 bins) for a total of 120 bins. The particlesmore » with diameters from 1 to 40 nm are resolved using an additional 8 size bins to calculate NPF. The ATRAS module was implemented in the WRF-chem model and applied to examine the sensitivity of simulated mass, number, size distributions, and optical and radiative parameters of aerosols to NPF, BC aging and SOA processes over East Asia during the spring of 2009. BC absorption enhancement by coating materials was about 50% over East Asia during the spring, and the contribution of SOA processes to the absorption enhancement was estimated to be 10 – 20% over northern East Asia and 20 – 35% over southern East Asia. A clear north-south contrast was also found between the impacts of NPF and SOA processes on cloud condensation nuclei (CCN) concentrations: NPF increased CCN concentrations at higher supersaturations (smaller particles) over northern East Asia, whereas SOA increased CCN concentrations at lower supersaturations (larger particles) over southern East Asia. Application of ATRAS to East Asia also showed that the impact of each process on each optical and radiative parameter depended strongly on the process and the parameter in question. The module can be used in the future as a benchmark model to evaluate the accuracy of simpler aerosol models and examine interactions between NPF, BC aging, and SOA

Do people essentialize emotions? Individual differences in emotion essentialism and emotional experience.

PubMed

Lindquist, Kristen A; Gendron, Maria; Oosterwijk, Suzanne; Barrett, Lisa Feldman

2013-08-01

Many scientific models of emotion assume that emotion categories are natural kinds that carve nature at its joints. These beliefs remain strong, despite the fact that the empirical record on the issue has remained equivocal for over a century. In this research, the authors examined one reason for this situation: People essentialize emotion categories by assuming that members of the same category (e.g., fear) have a shared metaphysical essence (i.e., a common causal mechanism). In Study 1, the authors found that lay people essentialize emotions by assuming that instances of the same emotion category have a shared essence that defines them, even when their surface features differ. Study 2 extended these findings, demonstrating that lay people tend to essentialize categories the more a category is of the body (vs. the mind). In Study 3, we examined the links between emotion essentialism and the complexity of actual emotional experiences. In particular, we predicted and found that individuals who hold essentialist beliefs about emotions describe themselves as experiencing highly differentiated emotional experiences but do not show evidence of stronger emotional differentiation in their momentary ratings of experience in everyday life. Implications for the science of emotion are discussed. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Lgr4-mediated Wnt/β-catenin signaling in peritubular myoid cells is essential for spermatogenesis.

PubMed

Qian, Yu; Liu, Shijie; Guan, Yuting; Pan, Hongjie; Guan, Xin; Qiu, Zhongwei; Li, Liang; Gao, Na; Zhao, Yongxiang; Li, Xiaoying; Lu, Yan; Liu, Mingyao; Li, Dali

2013-04-01

Peritubular myoid cells (PMCs) are myofibroblast-like cells that surround the seminiferous tubules and play essential roles in male fertility. How these cells modulate spermatogenesis and the signaling pathways that are involved are largely unknown. Here we report that Lgr4 is selectively expressed in mouse PMCs in the testes, and loss of Lgr4 leads to germ cells arresting at meiosis I and then undergoing apoptosis. In PMCs of Lgr4 mutant mice, the expression of androgen receptor, alpha-smooth muscle actin and extracellular matrix proteins was dramatically reduced. Malfunctioning PMCs further affected Sertoli cell nuclear localization and functional protein expression in Lgr4(-/-) mice. In addition, Wnt/β-catenin signaling was activated in wild-type PMCs but attenuated in those of Lgr4(-/-) mice. When Wnt/β-catenin signaling was reactivated by crossing with Apc(min/+) mice or by Gsk3β inhibitor treatment, the Lgr4 deficiency phenotype in testis was partially rescued. Together, these data demonstrate that Lgr4 signaling through Wnt/β-catenin regulates PMCs and is essential for spermatogenesis.

Physical characteristics of GE Senographe Essential and DS digital mammography detectors.

PubMed

Ghetti, Caterina; Borrini, Adriano; Ortenzia, Ornella; Rossi, Raffaella; Ordóñez, Pedro L

2008-02-01

The purpose of this study was to investigate physical characteristics of two full field digital mammography (FFDM) systems (GE Senographe Essential and DS). Both are indirect conversion (x ray to light) alpha-Si flat panels coupled with a CsI(Tl) scintillator. The examined systems have the same pixel size (100 microm) but a different field of view: a conventional size 23 x 19.2 cm2 and a large field 24 X 30.7 cm2, specifically designed to image large breasts. In the GE Senographe Essential model relevant improvements in flat panel design were implemented and new deposition tools for metal, alpha-Si, and CsI(Tl) were introduced by GE. These changes in detector design are expected to be beneficial for advanced applications such as breast tomosynthesis. The presampling modulation transfer function (MTF), normalized noise power spectrum (NNPS), and detective quantum efficiency (DQE) were measured for a wide range of exposure (25-240 microGy) with a RQA-M2 technique (28 kVp with a Mo/Mo target/filter combination and 2 mm of additional aluminum filtration). At 1, 2, and at 4 lp/mm MTF is equal to 0.9, 0.76, and 0.46 for the conventional field detector and to 0.85, 0.59, and 0.24 for the large field detector. The latter detector exhibits an improved NNPS due to a lower electronic noise and a better DQE that reaches 60%. In addition a contrast-detail analysis was performed with CDMAM 3.4 phantom and CDCOM software: GE Senographe DS showed statistically significant poorer detection ability in comparison with the GE Senographe Essential. These results could have been expected, at least qualitatively, considering the relative DQE of the two systems.

Integrin-linked kinase interactions with ELMO2 modulate cell polarity.

PubMed

Ho, Ernest; Irvine, Tames; Vilk, Gregory J A; Lajoie, Gilles; Ravichandran, Kodi S; D'Souza, Sudhir J A; Dagnino, Lina

2009-07-01

Cell polarization is a key prerequisite for directed migration during development, tissue regeneration, and metastasis. Integrin-linked kinase (ILK) is a scaffold protein essential for cell polarization, but very little is known about the precise mechanisms whereby ILK modulates polarization in normal epithelia. Elucidating these mechanisms is essential to understand tissue morphogenesis, transformation, and repair. Here we identify a novel ILK protein complex that includes Engulfment and Cell Motility 2 (ELMO2). We also demonstrate the presence of RhoG in ILK-ELMO2 complexes, and the localization of this multiprotein species specifically to the leading lamellipodia of polarized cells. Significantly, the ability of RhoG to bind ELMO is crucial for ILK induction of cell polarization, and the joint expression of ILK and ELMO2 synergistically promotes the induction of front-rear polarity and haptotactic migration. This places RhoG-ELMO2-ILK complexes in a key position for the development of cell polarity and forward movement. Although ILK is a component of many diverse multiprotein species that may contribute to cell polarization, expression of dominant-negative ELMO2 mutants is sufficient to abolish the ability of ILK to promote cell polarization. Thus, its interaction with ELMO2 and RhoG is essential for the ability of ILK to induce front-rear cell polarity.

Essential Medicines in a High Income Country: Essential to Whom?

PubMed Central

2015-01-01

Objective To explore the perspectives of a diverse group of stakeholders engaged in medicines decision making around what constitutes an “essential” medicine, and how the Essential Medicines List (EML) concept functions in a high income country context. Methods In-depth qualitative semi-structured interviews were conducted with 32 Australian stakeholders, recognised as decision makers, leaders or advisors in the area of medicines reimbursement or supply chain management. Participants were recruited from government, pharmaceutical industry, pharmaceutical wholesale/distribution companies, medicines non-profit organisations, academic health disciplines, hospitals, and consumer groups. Perspectives on the definition and application of the EML concept in a high income country context were thematically analysed using grounded theory approach. Findings Stakeholders found it challenging to describe the EML concept in the Australian context because many perceived it was generally used in resource scarce settings. Stakeholders were unable to distinguish whether nationally reimbursed medicines were essential medicines in Australia. Despite frequent generic drug shortages and high prices paid by consumers, many struggled to describe how the EML concept applied to Australia. Instead, broad inclusion of consumer needs, such as rare and high cost medicines, and consumer involvement in the decision making process, has led to expansive lists of nationally subsidised medicines. Therefore, improved communication and coordination is needed around shared interests between stakeholders regarding how medicines are prioritised and guaranteed in the supply chain. Conclusions This study showed that decision-making in Australia around reimbursement of medicines has strayed from the fundamental utilitarian concept of essential medicines. Many stakeholders involved in medicine reimbursement decisions and management of the supply chain did not consider the EML concept in their approach

Integration of Chinese medicine with Western medicine could lead to future medicine: molecular module medicine.

PubMed

Zhang, Chi; Zhang, Ge; Chen, Ke-ji; Lu, Ai-ping

2016-04-01

The development of an effective classification method for human health conditions is essential for precise diagnosis and delivery of tailored therapy to individuals. Contemporary classification of disease systems has properties that limit its information content and usability. Chinese medicine pattern classification has been incorporated with disease classification, and this integrated classification method became more precise because of the increased understanding of the molecular mechanisms. However, we are still facing the complexity of diseases and patterns in the classification of health conditions. With continuing advances in omics methodologies and instrumentation, we are proposing a new classification approach: molecular module classification, which is applying molecular modules to classifying human health status. The initiative would be precisely defining the health status, providing accurate diagnoses, optimizing the therapeutics and improving new drug discovery strategy. Therefore, there would be no current disease diagnosis, no disease pattern classification, and in the future, a new medicine based on this classification, molecular module medicine, could redefine health statuses and reshape the clinical practice.

Frankincense, pine needle and geranium essential oils suppress tumor progression through the regulation of the AMPK/mTOR pathway in breast cancer.

PubMed

Ren, Peng; Ren, Xiang; Cheng, Lei; Xu, Lixin

2018-01-01

BC (BC), as the most common malignancy in women worldwide, is associated with high morbidity and mortality. However, chemoresistance and toxicity are the main causes that limit the success of treatment in aggressive BC cases. Thus, there is a vital need to identify and develop novel therapeutic agents. Frankincense, pine needle and geranium essential oils have been reported to play critical biological activities in cancer. However, to the best of our knowledge whether frankincense, pine needle and geranium essential oils have any effect on the progression of BC in MCF-7 cells remains unclear. In the present study, we assessed the possible effects of frankincense, pine needle and geranium essential oils on cell viability, proliferation, migration and invasion as well as the possible mechanisms. MCF-7 cells were treated with oils, and associations with BC were investigated. In the present study, we clearly revealed that frankincense, pine needle and geranium essential oils suppressed cell viability, proliferation, migration and invasion in human BC MCF-7 cells. Further data demonstrated that frankincense, pine needle and geranium essential oils induced apoptosis, but did not affect cell cycle progression. Consistent with the in vitro activities, frankincense essential oil was effective in inhibiting tumor growth and inducing tumor cell apoptosis in a human BC mouse model. In addition, these 3 essential oils modulated the activity of the AMPK/mTOR signaling pathway. In conclusion, the present study indicated that frankincense, pine needle and geranium essential oils were involved in the progression of BC cells possibly through the AMPK/mTOR pathway.

Efficient modulation of γ-aminobutyric acid type A receptors by piperine derivatives.

PubMed

Schöffmann, Angela; Wimmer, Laurin; Goldmann, Daria; Khom, Sophia; Hintersteiner, Juliane; Baburin, Igor; Schwarz, Thomas; Hintersteininger, Michael; Pakfeifer, Peter; Oufir, Mouhssin; Hamburger, Matthias; Erker, Thomas; Ecker, Gerhard F; Mihovilovic, Marko D; Hering, Steffen

2014-07-10

Piperine activates TRPV1 (transient receptor potential vanilloid type 1 receptor) receptors and modulates γ-aminobutyric acid type A receptors (GABAAR). We have synthesized a library of 76 piperine analogues and analyzed their effects on GABAAR by means of a two-microelectrode voltage-clamp technique. GABAAR were expressed in Xenopus laevis oocytes. Structure-activity relationships (SARs) were established to identify structural elements essential for efficiency and potency. Efficiency of piperine derivatives was significantly increased by exchanging the piperidine moiety with either N,N-dipropyl, N,N-diisopropyl, N,N-dibutyl, p-methylpiperidine, or N,N-bis(trifluoroethyl) groups. Potency was enhanced by replacing the piperidine moiety by N,N-dibutyl, N,N-diisobutyl, or N,N-bistrifluoroethyl groups. Linker modifications did not substantially enhance the effect on GABAAR. Compound 23 [(2E,4E)-5-(1,3-benzodioxol-5-yl)-N,N-dipropyl-2,4-pentadienamide] induced the strongest modulation of GABAA (maximal GABA-induced chloride current modulation (IGABA-max = 1673% ± 146%, EC50 = 51.7 ± 9.5 μM), while 25 [(2E,4E)-5-(1,3-benzodioxol-5-yl)-N,N-dibutyl-2,4-pentadienamide] displayed the highest potency (EC50 = 13.8 ± 1.8 μM, IGABA-max = 760% ± 47%). Compound 23 induced significantly stronger anxiolysis in mice than piperine and thus may serve as a starting point for developing novel GABAAR modulators.

Attractiveness Modulates Neural Processing of Infant Faces Differently in Males and Females.

PubMed

Yin, Lijun; Fan, Mingxia; Lin, Lijia; Sun, Delin; Wang, Zhaoxin

2017-01-01

Consistent attention and proper processing of infant faces by adults are essential for infant survival. Previous behavioral studies showed gender differences in processing infant cues (e.g., crying, laughing or facial attractiveness) and more importantly, the efforts invested in nurturing offspring. The underlying neural mechanisms of processing unknown infant faces provide hints for understanding behavioral differences. This functional magnetic resonance imaging (fMRI) study recruited 32 unmarried adult (16 females and 16 males) participants to view unfamiliar infant faces and rate the attractiveness. Adult faces were also included. Behaviorally, despite that females and males showed no differences in attractiveness ratings of infant faces, a positive correlation was found between female's (but not male's) subjective liking for infants and attractiveness ratings of the infant faces. Functionally, brain activations to infant faces were modulated by attractiveness differently in males and females. Specifically, in female participants, activities in the ventromedial prefrontal cortex (vmPFC) and striatum/Nucleus Accumbens (NAcc) were positively modulated by infant facial attractiveness, and the modulation coefficients of these two regions were positively correlated. In male participants, infant facial attractiveness negatively modulated the activity in the dorsomedial prefrontal cortex (dmPFC). Our findings reveal that different neural mechanisms are involved in the processing of infant faces, which might lead to observed behavioral differences between males and females towards the baby.

Attractiveness Modulates Neural Processing of Infant Faces Differently in Males and Females

PubMed Central

Yin, Lijun; Fan, Mingxia; Lin, Lijia; Sun, Delin; Wang, Zhaoxin

2017-01-01

Consistent attention and proper processing of infant faces by adults are essential for infant survival. Previous behavioral studies showed gender differences in processing infant cues (e.g., crying, laughing or facial attractiveness) and more importantly, the efforts invested in nurturing offspring. The underlying neural mechanisms of processing unknown infant faces provide hints for understanding behavioral differences. This functional magnetic resonance imaging (fMRI) study recruited 32 unmarried adult (16 females and 16 males) participants to view unfamiliar infant faces and rate the attractiveness. Adult faces were also included. Behaviorally, despite that females and males showed no differences in attractiveness ratings of infant faces, a positive correlation was found between female’s (but not male’s) subjective liking for infants and attractiveness ratings of the infant faces. Functionally, brain activations to infant faces were modulated by attractiveness differently in males and females. Specifically, in female participants, activities in the ventromedial prefrontal cortex (vmPFC) and striatum/Nucleus Accumbens (NAcc) were positively modulated by infant facial attractiveness, and the modulation coefficients of these two regions were positively correlated. In male participants, infant facial attractiveness negatively modulated the activity in the dorsomedial prefrontal cortex (dmPFC). Our findings reveal that different neural mechanisms are involved in the processing of infant faces, which might lead to observed behavioral differences between males and females towards the baby. PMID:29184490

Transparent building-integrated PV modules. Phase 1: Comprehensive report

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

NONE

1998-09-28

This Comprehensive Report encompasses the activities that have been undertaken by Kiss + Cathcart, Architects, in conjunction with Energy Photovoltaics, Incorporated (EPV), to develop a flexible patterning system for thin-film photovoltaic (PV) modules for building applications. There are two basic methods for increasing transparency/light transmission by means of patterning the PV film: widening existing scribe lines, or scribing a second series of lines perpendicular to the first. These methods can yield essentially any degree of light transmission, but both result in visible patterns of light and dark on the panel surface. A third proposed method is to burn a gridmore » of dots through the films, independent of the normal cell scribing. This method has the potential to produce a light-transmitting panel with no visible pattern. Ornamental patterns at larger scales can be created using combinations of these techniques. Kiss + Cathcart, Architects, in conjunction with EPV are currently developing a complementary process for the large-scale lamination of thin-film PVs, which enables building integrated (BIPV) modules to be produced in sizes up to 48 in. x 96 in. Flexible laser patterning will be used for three main purposes, all intended to broaden the appeal of the product to the building sector: To create semitransparent thin-film modules for skylights, and in some applications, for vision glazing.; to create patterns for ornamental effects. This application is similar to fritted glass, which is used for shading, visual screening, graphics, and other purposes; and to allow BIPV modules to be fabricated in various sizes and shapes with maximum control over electrical characteristics.« less

Evaluation of an operational ocean model configuration at 1/12° spatial resolution for the Indonesian seas (NEMO2.3/INDO12) - Part 1: Ocean physics

NASA Astrophysics Data System (ADS)

Tranchant, Benoît; Reffray, Guillaume; Greiner, Eric; Nugroho, Dwiyoga; Koch-Larrouy, Ariane; Gaspar, Philippe

2016-03-01

INDO12 is a 1/12° regional version of the NEMO physical ocean model covering the whole Indonesian EEZ (Exclusive Economic Zone). It has been developed and is now running every week in the framework of the INDESO (Infrastructure Development of Space Oceanography) project implemented by the Indonesian Ministry of Marine Affairs and Fisheries. The initial hydrographic conditions as well as open-boundary conditions are derived from the operational global ocean forecasting system at 1/4° operated by Mercator Océan. Atmospheric forcing fields (3-hourly ECMWF (European Centre for Medium-Range Weather Forecast) analyses) are used to force the regional model. INDO12 is also forced by tidal currents and elevations, and by the inverse barometer effect. The turbulent mixing induced by internal tides is taken into account through a specific parameterisation. In this study we evaluate the model skill through comparisons with various data sets including outputs of the parent model, climatologies, in situ temperature and salinity measurements, and satellite data. The biogeochemical model results assessment is presented in a companion paper (Gutknecht et al., 2015). The simulated and altimeter-derived Eddy Kinetic Energy fields display similar patterns and confirm that tides are a dominant forcing in the area. The volume transport of the Indonesian throughflow (ITF) is in good agreement with the INSTANT estimates while the transport through Luzon Strait is, on average, westward but probably too weak. Compared to satellite data, surface salinity and temperature fields display marked biases in the South China Sea. Significant water mass transformation occurs along the main routes of the ITF and compares well with observations. Vertical mixing is able to modify the South and North Pacific subtropical water-salinity maximum as seen in T-S diagrams. In spite of a few weaknesses, INDO12 proves to be able to provide a very realistic simulation of the ocean circulation and water mass

Intracellular Signal Modulation by Nanomaterials

PubMed Central

Hussain, Salik; Garantziotis, Stavros; Rodrigues-Lima, Fernando; Dupret, Jean-Marie; Baeza-Squiban, Armelle; Boland, Sonja

2016-01-01

A thorough understanding of the interactions of nanomaterials with biological systems and the resulting activation of signal transduction pathways is essential for the development of safe and consumer friendly nanotechnology. Here we present an overview of signaling pathways induced by nanomaterial exposures and describe the possible correlation of their physicochemical characteristics with biological outcomes. In addition to the hierarchical oxidative stress model and a review of the intrinsic and cell-mediated mechanisms of reactive Oxygen species (ROS) generating capacities of nanomaterials, we also discuss other oxidative stress dependent and independent cellular signaling pathways. Induction of the inflammasome, calcium signaling, and endoplasmic reticulum stress are reviewed. Furthermore, the uptake mechanisms can crucially affect the cytotoxicity of nanomaterials and membrane-dependent signaling pathways can be responsible for cellular effects of nanomaterials. Epigenetic regulation by nanomaterials effects of nanoparticle-protein interactions on cell signaling pathways, and the induction of various cell death modalities by nanomaterials are described. We describe the common trigger mechanisms shared by various nanomaterials to induce cell death pathways and describe the interplay of different modalities in orchestrating the final outcome after nanomaterial exposures. A better understanding of signal modulations induced by nanomaterials is not only essential for the synthesis and design of safer nanomaterials but will also help to discover potential nanomedical applications of these materials. Several biomedical applications based on the different signaling pathways induced by nanomaterials are already proposed and will certainly gain a great deal of attraction in the near future. PMID:24683030

Cytokine Signaling Modulates Blood-Brain Barrier Function

PubMed Central

Pan, Weihong; Stone, Kirsten P.; Hsuchou, Hung; Manda, Vamshi K.; Zhang, Yan; Kastin, Abba J.

2014-01-01

The blood-brain barrier (BBB) provides a vast interface for cytokines to affect CNS function. The BBB is a target for therapeutic intervention. It is essential, therefore, to understand how cytokines interact with each other at the level of the BBB and how secondary signals modulate CNS functions beyond the BBB. The interactions between cytokines and lipids, however, have not been fully addressed at the level of the BBB. Here, we summarize current understanding of the localization of cytokine receptors and transporters in specific membrane microdomains, particularly lipid rafts, on the luminal (apical) surface of the microvascular endothelial cells composing the BBB. We then illustrate the clinical context of cytokine effects on the BBB by neuroendocrine regulation and amplification of inflammatory signals. Two unusual aspects discussed are signaling crosstalk by different classes of cytokines and genetic regulation of drug efflux transporters. We also introduce a novel area of focus on how cytokines may act through nuclear hormone receptors to modulate efflux transporters and other targets. A specific example discussed is the ATP-binding cassette transporter-1 (ABCA-1) that regulates lipid metabolism. Overall, cytokine signaling at the level of the BBB is a crucial feature of the dynamic regulation that can rapidly change BBB function and affect brain health and disease. PMID:21834767

Autophagy modulation as a potential therapeutic target for diverse diseases

PubMed Central

Rubinsztein, David C.; Codogno, Patrice; Levine, Beth

2012-01-01

Autophagy is an essential, conserved lysosomal degradation pathway that controls the quality of the cytoplasm by eliminating protein aggregates and damaged organelles. It begins when double-membraned autophagosomes engulf portions of the cytoplasm, which is followed by fusion of these vesicles with lysosomes and degradation of the autophagic contents. In addition to its vital homeostatic role, this degradation pathway is involved in various human disorders, including metabolic conditions, neurodegenerative diseases, cancers and infectious diseases. This article provides an overview of the mechanisms and regulation of autophagy, the role of this pathway in disease and strategies for therapeutic modulation. PMID:22935804

In Situ Caging of Biomolecules in Graphene Hybrids for Light Modulated Bioactivity.

PubMed

Cheng, Gong; Han, Xiao-Hui; Hao, Si-Jie; Nisic, Merisa; Zheng, Si-Yang

2018-01-31

Remote and noninvasive modulation of protein activity is essential for applications in biotechnology and medicine. Optical control has emerged as the most attractive approach owing to its high spatial and temporal resolutions; however, it is challenging to engineer light responsive proteins. In this work, a near-infrared (NIR) light-responsive graphene-silica-trypsin (GST) nanoreactor is developed for modulating the bioactivity of trypsin molecules. Biomolecules are spatially confined and protected in the rationally designed compartment architecture, which not only reduces the possible interference but also boosts the bioreaction efficiency. Upon NIR irradiation, the photothermal effect of the GST nanoreactor enables the ultrafast in situ heating for remote activation and tuning of the bioactivity. We apply the GST nanoreactor for remote and ultrafast proteolysis of proteins, which remarkably enhances the proteolysis efficiency and reduces the bioreaction time from the overnight of using free trypsin to seconds. We envision that this work not only provides a promising tool of ultrafast and remotely controllable proteolysis for in vivo proteomics in study of tissue microenvironment and other biomedical applications but also paves the way for exploring smart artificial nanoreactors in biomolecular modulation to gain insight in dynamic biological transformation.

Essential and non-essential paediatric surgery: implications for the future delivery of state health care in the UK.

PubMed

Farrelly, Paul J; Losty, Paul D

2015-09-01

Delivery of health care in the UK faces enormous challenges with the Department of Health driving significant financial cost savings to ensure viability of public health services. We have analysed and modelled the concept of 'essential' and 'non-essential' paediatric surgery linked to the delivery of children's surgery in the NHS in England. Operation codes for surgical operations in newborns, children and adolescents were identified and Healthcare Resource Group tariffs-£Stg matched. Operations were designated as 'essential' or 'non-essential' based on the criteria-(1) life saving-neonatal surgery, emergency general surgery of childhood, cancer surgery; (2) debility if uncorrected; (3) aesthetics and (4) culture/attitude. Hospital Episode Statistics (HES) data were accessed and sampled for the total number of paediatric surgical operations-(age range 0-14 years) performed in NHS hospitals from 2009 to 2010. Annual costs (£) of both 'essential' and 'non-essential' operations were then calculated. The commonest 'essential' operations performed in children and adolescents in the year 2009-2010 was appendicectomy at a cost of over £51 million pounds. Costs of performing a selection of 'non-essential' paediatric surgery operations were >£14 million pounds/year. The NHs funds for example almost 11,000 paediatric circumcisions annually at a cost of >£8 million pounds-50% are performed for non-therapeutic reasons. Surgeons must engage and work actively with health care systems to ensure diminishing financial resources prioritise 'essential' operations for children. Commissioners must embrace evidence-based surgery. 'Essential' and 'non-essential' surgery has wide implications for the sustainability of the NHS and concepts herein developed can be applied to nations worldwide.

External amplitude and frequency modulation of a terahertz quantum cascade laser using metamaterial/graphene devices.

PubMed

Kindness, S J; Jessop, D S; Wei, B; Wallis, R; Kamboj, V S; Xiao, L; Ren, Y; Braeuninger-Weimer, P; Aria, A I; Hofmann, S; Beere, H E; Ritchie, D A; Degl'Innocenti, R

2017-08-09

Active control of the amplitude and frequency of terahertz sources is an essential prerequisite for exploiting a myriad of terahertz applications in imaging, spectroscopy, and communications. Here we present a optoelectronic, external modulation technique applied to a terahertz quantum cascade laser which holds the promise of addressing a number of important challenges in this research area. A hybrid metamaterial/graphene device is implemented into an external cavity set-up allowing for optoelectronic tuning of feedback into a quantum cascade laser. We demonstrate powerful, all-electronic, control over the amplitude and frequency of the laser output. Full laser switching is performed by electrostatic gating of the metamaterial/graphene device, demonstrating a modulation depth of 100%. External control of the emission spectrum is also achieved, highlighting the flexibility of this feedback method. By taking advantage of the frequency dispersive reflectivity of the metamaterial array, different modes of the QCL output are selectively suppressed using lithographic tuning and single mode operation of the multi-mode laser is enforced. Side mode suppression is electrically modulated from ~6 dB to ~21 dB, demonstrating active, optoelectronic modulation of the laser frequency content between multi-mode and single mode operation.

New Perspectives on the Essential Trace Elements.

ERIC Educational Resources Information Center

Frieden, Earl

1985-01-01

Provides a comprehensive overview of the 19 essential trace elements, examining: the concept of essentiality; evolution of these elements; possible future essential elements; the lanthanides and actinides; how essential trace elements work; the metalloenzymes; the nonmetals; iodine and the thyroid hormones; and antagonism among these elements. (JN)

Module utilization committee

NASA Technical Reports Server (NTRS)

Volkmer, K.; Praver, G.

1984-01-01

Photovoltaic collector modules were declared surplus to the needs of the U.S. Dept. of Energy. The Module Utilization Committee was formed to make appropriate disposition of the surplus modules on a national basis and to act as a broker for requests for these modules originating outside of the National Photovoltaics Program.

Measuring nursing essential contributions to quality patient care outcomes.

PubMed

Wolgast, Kelly A; Taylor, Katherine; Garcia, Dawn; Watkins, Miko

2011-01-01

Workload Management System for Nursing (WMSN) is a core Army Medical Department business system that has provided near real-time, comprehensive nursing workload and manpower data for decision making at all levels for over 25 years. The Army Manpower Requirements and Documentation Agency populates data from WMSN into the Manpower Staffing Standards System (Inpatient module within Automated Staffing Assessment Model). The current system, Workload Management System for Nursing Internet (WMSNi), is an interim solution that requires additional functionalities for modernization and integration at the enterprise level. The expanding missions and approved requirements for WMSNi support strategic initiatives on the Army Medical Command balanced scorecard and require continued sustainment for multiple personnel and manpower business processes for both inpatient and outpatient nursing care. This system is currently being leveraged by the TRICARE Management Activity as an interim multiservice solution, and is being used at 24 Army medical treatment facilities. The evidenced-based information provided to Army decision makers through the methods used in the WMSNi will be essential across the Army Medical Command throughout the system's life cycle.

Essential pitfalls in "essential” tremor

PubMed Central

Espay, AJ; Lang, AE; Erro, R; Merola, A; Fasano, A; Berardelli, A; Bhatia, KP

2016-01-01

While essential tremor has been considered the most common movement disorder, it has largely remained a diagnosis of exclusion: many tremor and non-tremor features must be absent for the clinical diagnosis to stand. The clinical features of “essential tremor” overlap with or may be part of other tremor disorders and, not surprisingly, this prevalent familial disorder has remained without a gene identified, without a consistent natural history, and without an acceptable pathology or pathophysiologic underpinning. The collective evidence suggests that under the rubric of essential tremor there exists multiple unique diseases, some of which represent cerebellar dysfunction, but for which there is no intrinsic “essence” other than a common oscillatory behavior on posture and action. One approach may be to use the term “essential tremor” only as a transitional node in the deep phenotyping of tremor disorders based on historical, phenomenological, and neurophysiological features, to facilitate its etiologic diagnosis or serve for future gene- and biomarker-discovery efforts. This approach deemphasizes essential tremor as a diagnostic entity and facilitates the understanding of the underlying disorders in order to develop biologically tailored diagnostic and therapeutic strategies. PMID:28116753

Essential Oils, Part I: Introduction.

PubMed

de Groot, Anton C; Schmidt, Erich

2016-01-01

Essential oils are widely used in the flavor, food, fragrance, and cosmetic industries in many applications. Contact allergy to them is well known and has been described for 80 essential oils. The relevance of positive patch test reactions often remains unknown. Knowledge of the chemical composition of essential oils among dermatologists is suspected to be limited, as such data are published in journals not read by the dermatological community. Therefore, the authors have fully reviewed and published the literature on contact allergy to and chemical composition of essential oils. Selected topics from this publication will be presented in abbreviated form in Dermatitis starting with this issue, including I. Introduction; II. General aspects; III. Chemistry; IV. General aspects of contact allergy; V. Peppermint oil, lavender oil and lemongrass oil; VI: Sandalwood oil, ylang-ylang oil, and jasmine absolute.

Auditory sensitivity to spectral modulation phase reversal as a function of modulation depth

PubMed Central

Grose, John

2018-01-01

The present study evaluated auditory sensitivity to spectral modulation by determining the modulation depth required to detect modulation phase reversal. This approach may be preferable to spectral modulation detection with a spectrally flat standard, since listeners appear unable to perform the task based on the detection of temporal modulation. While phase reversal thresholds are often evaluated by holding modulation depth constant and adjusting modulation rate, holding rate constant and adjusting modulation depth supports rate-specific assessment of modulation processing. Stimuli were pink noise samples, filtered into seven octave-wide bands (0.125–8 kHz) and spectrally modulated in dB. Experiment 1 measured performance as a function of modulation depth to determine appropriate units for adaptive threshold estimation. Experiment 2 compared thresholds in dB for modulation detection with a flat standard and modulation phase reversal; results supported the idea that temporal cues were available at high rates for the former but not the latter. Experiment 3 evaluated spectral modulation phase reversal thresholds for modulation that was restricted to either one or two neighboring bands. Flanking bands of unmodulated noise had a larger detrimental effect on one-band than two-band targets. Thresholds for high-rate modulation improved with increasing carrier frequency up to 2 kHz, whereas low-rate modulation appeared more consistent across frequency, particularly in the two-band condition. Experiment 4 measured spectral weights for spectral modulation phase reversal detection and found higher weights for bands in the spectral center of the stimulus than for the lowest (0.125 kHz) or highest (8 kHz) band. Experiment 5 compared performance for highly practiced and relatively naïve listeners, and found weak evidence of a larger practice effect at high than low spectral modulation rates. These results provide preliminary data for a task that may provide a better estimate

The Mediterranean Forecasting System: recent developments

NASA Astrophysics Data System (ADS)

Tonani, Marina; Oddo, Paolo; Korres, Gerasimos; Clementi, Emanuela; Dobricic, Srdjan; Drudi, Massimiliano; Pistoia, Jenny; Guarnieri, Antonio; Romaniello, Vito; Girardi, Giacomo; Grandi, Alessandro; Bonaduce, Antonio; Pinardi, Nadia

2014-05-01

Recent developments of the Mediterranean Monitoring and Forecasting Centre of the EU-Copernicus marine service, the Mediterranean Forecasting System (MFS), are presented. MFS provides forecast, analysis and reanalysis for the physical and biogeochemical parameters of the Mediterranean Sea. The different components of the system are continuously updated in order to provide to the users the best available product. This work is focus on the physical component of the system. The physical core of MFS is composed by an ocean general circulation model (NEMO) coupled with a spectral wave model (Wave Watch-III). The NEMO model provides to WW-III surface currents and SST fields, while WW-III returns back to NEMO the neutral component of the surface drag coefficient. Satellite Sea Level Anomaly observations and in-situ T & S vertical profiles are assimilated into this system using a variational assimilation scheme based on 3DVAR (Dobricic, 2008) . Sensitive experiments have been performed in order to assess the impact of the assimilation of the latest available SLA missions, Altika and Cryosat together with the long term available mission of Jason2. The results show a significant improvement of the MFS skill due to the multi-mission along track assimilation. The primitive equations module has been recently upgraded with the introduction of the atmospheric pressure term and a new, explicit, numerical scheme has been adopted to solve the barotropic component of the equations of motion. The SLA satellite observations for data assimilation have been consequently modified in order to account for the new atmospheric pressure term introduced in the equations. This new system has been evaluated using tide gauge coastal buoys and the satellite along track data. The quality of the SSH has improved significantly while a minor impact has been observed on the other state variables (temperature, salinity and currents). Experiments with a higher resolution NWP (numerical weather prediction

Structure and mechanism of the essential two-component signal-transduction system WalKR in Staphylococcus aureus

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

Ji, Quanjiang; Chen, Peter J.; Qin, Guangrong

Most low GC Gram-positive bacteria possess an essential walKR two-component system (TCS) for signal transduction involved in regulating cell wall homoeostasis. Despite the well-established intracellular regulatory mechanism, the role of this TCS in extracellular signal recognition and factors that modulate the activity of this TCS remain largely unknown. Here we identify the extracellular receptor of the kinase ‘WalK’ (erWalK) as a key hub for bridging extracellular signal input and intracellular kinase activity modulation in Staphylococcus aureus. Characterization of the crystal structure of erWalK revealed a canonical Per-Arnt-Sim (PAS) domain for signal sensing. Single amino-acid mutation of potential signal-transduction residues resultedmore » in severely impaired function of WalKR. A small molecule derived from structure-based virtual screening against erWalK is capable of selectively activating the walKR TCS. Lastly, the molecular level characterization of erWalK will not only facilitate exploration of natural signal(s) but also provide a template for rational design of erWalK inhibitors.« less

Structure and mechanism of the essential two-component signal-transduction system WalKR in Staphylococcus aureus

DOE PAGES

Ji, Quanjiang; Chen, Peter J.; Qin, Guangrong; ...

2016-03-18

Most low GC Gram-positive bacteria possess an essential walKR two-component system (TCS) for signal transduction involved in regulating cell wall homoeostasis. Despite the well-established intracellular regulatory mechanism, the role of this TCS in extracellular signal recognition and factors that modulate the activity of this TCS remain largely unknown. Here we identify the extracellular receptor of the kinase ‘WalK’ (erWalK) as a key hub for bridging extracellular signal input and intracellular kinase activity modulation in Staphylococcus aureus. Characterization of the crystal structure of erWalK revealed a canonical Per-Arnt-Sim (PAS) domain for signal sensing. Single amino-acid mutation of potential signal-transduction residues resultedmore » in severely impaired function of WalKR. A small molecule derived from structure-based virtual screening against erWalK is capable of selectively activating the walKR TCS. Lastly, the molecular level characterization of erWalK will not only facilitate exploration of natural signal(s) but also provide a template for rational design of erWalK inhibitors.« less

Amplitude modulation detection with concurrent frequency modulation.

PubMed

Nagaraj, Naveen K

2016-09-01

Human speech consists of concomitant temporal modulations in amplitude and frequency that are crucial for speech perception. In this study, amplitude modulation (AM) detection thresholds were measured for 550 and 5000 Hz carriers with and without concurrent frequency modulation (FM), at AM rates crucial for speech perception. Results indicate that adding 40 Hz FM interferes with AM detection, more so for 5000 Hz carrier and for frequency deviations exceeding the critical bandwidth of the carrier frequency. These findings suggest that future cochlear implant processors, encoding speech fine-structures may consider limiting the FM to narrow bandwidth and to low frequencies.

Sensitive voltammetric determination of thymol in essential oil of Carum copticum seeds using boron-doped diamond electrode.

PubMed

Stanković, Dalibor M

2015-10-01

Essential oil of Carum copticum seeds, obtained from a local shop, was extracted and content of thymol was analyzed using square-wave voltammetry at boron-doped diamond electrode. The effect of various parameters, such as pH of supporting electrolyte and square-wave voltammetric parameters (modulation amplitude and frequency), was examined. In Britton-Robinson buffer solution (pH 4), thymol provided a single and oval-shaped irreversible oxidation peak at +1.13 V versus silver/silver chloride potassium electrode (3M). Under optimal experimental conditions, a plot of peak height against concentration of thymol was found to be linear over the range of 4 to 100μM consisting of two linear ranges: from 4 to 20μM (R(2)=0.9964) and from 20 to 100μM (R(2)=0.9993). The effect of potential interferences such as p-cymene and γ-terpinene (major components in essential oil of C. copticum seeds) was evaluated. Thus, the proposed method displays a sufficient selectivity toward thymol with a detection limit of 3.9μM, and it was successfully applied for the determination of thymol in essential oil of C. copticum seeds. The Prussian blue method was used for validation of the proposed electroanalytical method. Copyright © 2015 Elsevier Inc. All rights reserved.

Mid-infrared transmitter and receiver modules for free-space optical communication.

PubMed

Hao, Qiang; Zhu, Guoshen; Yang, Song; Yang, Kangwen; Duan, Tao; Xie, Xiaoping; Huang, Kun; Zeng, Heping

2017-03-10

We report on the experimental implementation of single-frequency fiber-laser pumped mid-infrared (mid-IR) transmitter and receiver modules for free-space communications. These modules enable frequency upconversion and downconversion between the 1550-nm telecom wavelength and the mid-IR, thus providing essential free-space transmission links with mid-IR single-frequency lasers in the 3.6 μm region. Specifically, based on difference frequency generation (DFG) in MgO-doped periodically poled LiNbO₃ (MgO:PPLN), the mid-IR transmitter produces 9.3-mW power at 3594 nm with 5-W pump power at 1083 nm (<10  kHz linewidth) and 3-W signal power at 1550 nm (<10  kHz linewidth), and the mid-IR receiver reproduces 12-μW power at 1550 nm with 4.7-W pump power at 1083 nm and 5-mW laser at 3594 nm. The whole modules are integrated into portable and compact devices by incorporating single-frequency fiber lasers, fiber amplifiers, DFG units, and related electronic circuits. In addition, the uses of all polarization-maintaining fiber configuration and well-controlled heat dissipation make the mid-IR transmitter and receiver exhibit a long-term stability.

Responsive nanoporous metals: recoverable modulations on strength and shape by watering

NASA Astrophysics Data System (ADS)

Ye, Xing-Long; Liu, Ling-Zhi; Jin, Hai-Jun

2016-08-01

Many biological materials can readily modulate their mechanical properties and shape by interacting with water in the surrounding environment, which is essential to their high performance in application. In contrast, typical inorganic materials (such as the metals) cannot change their strength and shape without involving thermal/mechanical treatments. By introducing nano-scale porous structure and exploiting a simple physical concept—the water-capillarity in nanopores, here we report that a ‘dead’ metal can be transformed into a ‘smart’ material with water-responsive properties. We demonstrate that the apparent strength, volume and shape of nanoporous Au and Au(Pt) can be modulated in situ, dramatically and recoverably, in response to water-dipping and partial-drying. The amplitude of strength-modulation reaches 20 MPa, which is nearly 50% of the yield strength at initial state. This approach also leads to reversible length change up to 1.3% in nanoporous Au and a large reversible bending motion of a bi-layer strip with tip displacement of ˜20 mm, which may be used for actuation. This method is simple and effective, occurring in situ under ambient conditions and requiring no external power, analogous to biological materials. The findings may open up novel applications in many areas such as micro-robotics and bio-medical devices.

A forward genetic screen reveals essential and non-essential RNAi factors in Paramecium tetraurelia

PubMed Central

Marker, Simone; Carradec, Quentin; Tanty, Véronique; Arnaiz, Olivier; Meyer, Eric

2014-01-01

In most eukaryotes, small RNA-mediated gene silencing pathways form complex interacting networks. In the ciliate Paramecium tetraurelia, at least two RNA interference (RNAi) mechanisms coexist, involving distinct but overlapping sets of protein factors and producing different types of short interfering RNAs (siRNAs). One is specifically triggered by high-copy transgenes, and the other by feeding cells with double-stranded RNA (dsRNA)-producing bacteria. In this study, we designed a forward genetic screen for mutants deficient in dsRNA-induced silencing, and a powerful method to identify the relevant mutations by whole-genome sequencing. We present a set of 47 mutant alleles for five genes, revealing two previously unknown RNAi factors: a novel Paramecium-specific protein (Pds1) and a Cid1-like nucleotidyl transferase. Analyses of allelic diversity distinguish non-essential and essential genes and suggest that the screen is saturated for non-essential, single-copy genes. We show that non-essential genes are specifically involved in dsRNA-induced RNAi while essential ones are also involved in transgene-induced RNAi. One of the latter, the RNA-dependent RNA polymerase RDR2, is further shown to be required for all known types of siRNAs, as well as for sexual reproduction. These results open the way for the dissection of the genetic complexity, interconnection, mechanisms and natural functions of RNAi pathways in P. tetraurelia. PMID:24860163

Whole Module Offgas Test Report: Space-Xl Dragon Module

NASA Technical Reports Server (NTRS)

James, John T.

2012-01-01

On September 26 and September 28,2012 a chemist from the JSC Toxicology Group acquired samples of air in 500 m1 evacuated canisters from the sealed Space-Xl Dragon Module. One sample was also acquired from Space-X Facility near the module at the start of the test. Samples of the module air were taken in triplicate once the module had been sealed, and then taken again in triplicate 1.98 days later. Ofthe triplicate samples, the first served as a line purge, and the last two were analyzed. The results of 5 samples are reported.

Prolonged exposure to salt stress affects specialized metabolites-artemisinin and essential oil accumulation in Artemisia annua L.: metabolic acclimation in preferential favour of enhanced terpenoid accumulation accompanying vegetative to reproductive phase transition.

PubMed

Yadav, Ritesh Kumar; Sangwan, Rajender Singh; Srivastava, Avadesh K; Sangwan, Neelam S

2017-01-01

Artemisia annua accumulates substantial quantities of unique and highly useful antimalarial sesquiternoid artemisinin and related phytomolecules as well as its characteristic essential oil in its glandular trichomes. The phytomolecules are mainly produced in its leaves and inflorescences. Artemisia annua plants were grown under NaCl salinity (50, 100 and 200 mM) stress conditions imposed throughout the entire life cycle of the plant. Results revealed that specialized metabolites like artemisinin, arteannuin-B, artemisinic acid + dihydroartemisinic acid and essential oil accumulation were positively modulated by NaCl salinity stress. Interestingly, total content of monoterpenoids and sesquiterpenoids of essential oil was induced by NaCl salinity treatment, contrary to previous observations. Production of camphor, the major essential oil constituent was induced under the influence of treatment. The metabolic acclimation and manifestations specific to terpenoid pathway are analysed vis-a-vis vegetative to reproductive periods and control of the modulation. WRKY and CYP71AV1 play a key role in mediating the responses through metabolism in glandular trichomes. The distinctness of the salinity induced responses is discussed in light of differential mechanism of adaptation to abiotic stresses and their impact on terpenoid-specific metabolic adjustments in A. annua. Results provide potential indications of possible adaptation of A. annua under saline conditions for agrarian techno-economic benefaction.

TrackMate: An open and extensible platform for single-particle tracking.

PubMed

Tinevez, Jean-Yves; Perry, Nick; Schindelin, Johannes; Hoopes, Genevieve M; Reynolds, Gregory D; Laplantine, Emmanuel; Bednarek, Sebastian Y; Shorte, Spencer L; Eliceiri, Kevin W

2017-02-15

We present TrackMate, an open source Fiji plugin for the automated, semi-automated, and manual tracking of single-particles. It offers a versatile and modular solution that works out of the box for end users, through a simple and intuitive user interface. It is also easily scriptable and adaptable, operating equally well on 1D over time, 2D over time, 3D over time, or other single and multi-channel image variants. TrackMate provides several visualization and analysis tools that aid in assessing the relevance of results. The utility of TrackMate is further enhanced through its ability to be readily customized to meet specific tracking problems. TrackMate is an extensible platform where developers can easily write their own detection, particle linking, visualization or analysis algorithms within the TrackMate environment. This evolving framework provides researchers with the opportunity to quickly develop and optimize new algorithms based on existing TrackMate modules without the need of having to write de novo user interfaces, including visualization, analysis and exporting tools. The current capabilities of TrackMate are presented in the context of three different biological problems. First, we perform Caenorhabditis-elegans lineage analysis to assess how light-induced damage during imaging impairs its early development. Our TrackMate-based lineage analysis indicates the lack of a cell-specific light-sensitive mechanism. Second, we investigate the recruitment of NEMO (NF-κB essential modulator) clusters in fibroblasts after stimulation by the cytokine IL-1 and show that photodamage can generate artifacts in the shape of TrackMate characterized movements that confuse motility analysis. Finally, we validate the use of TrackMate for quantitative lifetime analysis of clathrin-mediated endocytosis in plant cells. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

An integrative machine learning strategy for improved prediction of essential genes in Escherichia coli metabolism using flux-coupled features.

PubMed

Nandi, Sutanu; Subramanian, Abhishek; Sarkar, Ram Rup

2017-07-25

Prediction of essential genes helps to identify a minimal set of genes that are absolutely required for the appropriate functioning and survival of a cell. The available machine learning techniques for essential gene prediction have inherent problems, like imbalanced provision of training datasets, biased choice of the best model for a given balanced dataset, choice of a complex machine learning algorithm, and data-based automated selection of biologically relevant features for classification. Here, we propose a simple support vector machine-based learning strategy for the prediction of essential genes in Escherichia coli K-12 MG1655 metabolism that integrates a non-conventional combination of an appropriate sample balanced training set, a unique organism-specific genotype, phenotype attributes that characterize essential genes, and optimal parameters of the learning algorithm to generate the best machine learning model (the model with the highest accuracy among all the models trained for different sample training sets). For the first time, we also introduce flux-coupled metabolic subnetwork-based features for enhancing the classification performance. Our strategy proves to be superior as compared to previous SVM-based strategies in obtaining a biologically relevant classification of genes with high sensitivity and specificity. This methodology was also trained with datasets of other recent supervised classification techniques for essential gene classification and tested using reported test datasets. The testing accuracy was always high as compared to the known techniques, proving that our method outperforms known methods. Observations from our study indicate that essential genes are conserved among homologous bacterial species, demonstrate high codon usage bias, GC content and gene expression, and predominantly possess a tendency to form physiological flux modules in metabolism.

Galois Module Structure of Lubin-Tate Modules

NASA Astrophysics Data System (ADS)

Tomaskovic-Moore, Sebastian

Let L/K be a finite, Galois extension of local or global fields. In the classical setting of additive Galois modules, the ring of integers OL of L is studied as a module for the group ring OKG, where G is the Galois group of L/K. When K is a p-adic field, we also find a structure of OKG module when we replace OL with the group of points in OL of a Lubin-Tate formal group defined over K. For this new Galois module we find an analogue of the normal basis theorem. When K is a proper unramified extension of Qp , we show that some eigenspaces for the Teichmuller character are not free. We also adapt certain cases of E. Noether's result on normal integral bases for tame extensions. Finally, for wild extensions we define a version of Leopoldt's associated order and demonstrate in a specific case that it is strictly larger than the integral group ring.

46 CFR 252.21 - Essential service requirement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Essential service requirement. 252.21 Section 252.21... § 252.21 Essential service requirement. (a) Essential service. A vessel which is not subject to a... separate agreement, shall be deemed to be in an essential service, within the meaning of section 211(b) of...

Enhancing biological relevance of a weighted gene co-expression network for functional module identification.

PubMed

Prom-On, Santitham; Chanthaphan, Atthawut; Chan, Jonathan Hoyin; Meechai, Asawin

2011-02-01

Relationships among gene expression levels may be associated with the mechanisms of the disease. While identifying a direct association such as a difference in expression levels between case and control groups links genes to disease mechanisms, uncovering an indirect association in the form of a network structure may help reveal the underlying functional module associated with the disease under scrutiny. This paper presents a method to improve the biological relevance in functional module identification from the gene expression microarray data by enhancing the structure of a weighted gene co-expression network using minimum spanning tree. The enhanced network, which is called a backbone network, contains only the essential structural information to represent the gene co-expression network. The entire backbone network is decoupled into a number of coherent sub-networks, and then the functional modules are reconstructed from these sub-networks to ensure minimum redundancy. The method was tested with a simulated gene expression dataset and case-control expression datasets of autism spectrum disorder and colorectal cancer studies. The results indicate that the proposed method can accurately identify clusters in the simulated dataset, and the functional modules of the backbone network are more biologically relevant than those obtained from the original approach.

PRESYNAPTIC DOPAMINE MODULATION BY STIMULANT SELF ADMINISTRATION

PubMed Central

España, Rodrigo A.; Jones, Sara R.

2013-01-01

The mesolimbic dopamine system is an essential participant in the initiation and modulation of various forms of goal-directed behavior, including drug reinforcement and addiction processes. Dopamine neurotransmission is increased by acute administration of all drugs of abuse, including the stimulants cocaine and amphetamine. Chronic exposure to these drugs via voluntary self-administration provides a model of stimulant abuse that is useful in evaluating potential behavioral and neurochemical adaptations that occur during addiction. This review describes commonly used methodologies to measure dopamine and baseline parameters of presynaptic dopamine regulation, including exocytotic release and reuptake through the dopamine transporter in the nucleus accumbens core, as well as dramatic adaptations in dopamine neurotransmission and drug sensitivity that occur with acute non-contingent and chronic, contingent self-administration of cocaine and amphetamine. PMID:23277050

Model Development of Degradation of PV Modules Backsheet with Locating Place of Module

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

Kempe, Michael D; Wang, Yu; Fairbrother, Andrew

Performance of a photovoltaic (PV) module is related to the micro-environment around the module. The position of photovoltaic modules in an array row have a large effect on the yellowing and gloss of PV module backsheet exposed in Dfa climatic zone (Gaithersburg, MD) with a polyethylene naphthalate (PEN) outer layer. Stress/Response models of yellowing and gloss-losing as function of location parameters of module, including the shed, row, measurement position in a same module and the distance of module location to the row center, are under development. The module installation height had the greatest influence on degradation of PEN PV backsheetmore » in the Dfa climatic zone. The module backsheets at the end of an array have higher degradation rate (edge effect). The edge effect decreases with increasing of module installation heights.« less

Essential Tremor with Aspartic Acidemia.

PubMed

Miura, Shiroh; Fujioka, Ryuta; Taniwaki, Takayuki

2017-05-08

We describe two cases of typical essential tremor with aspartic acidemia and mildly increased concentrations of plasma glutamic acid. Although this is a preliminary report, we emphasize the possibility of using amino acids, including aspartic acid, as biomarkers for the detection of essential tremor.

An essential memory trace found.

PubMed

Thompson, Richard F

2013-10-01

I argue here that we have succeeded in localizing an essential memory trace for a basic form of associative learning and memory--classical conditioning of discrete responses learned with an aversive stimulus--to the anterior interpositus nucleus of the cerebellum. We first identified the entire essential circuit, using eyelid conditioning as the model system, and used reversible inactivation, during training, of critical structures and pathways to localize definitively the essential memory trace. In recognition of the 30th anniversary of Behavioral Neuroscience, I highlight 1 paper (Tracy, Thompson, Krupa, & Thompson, 1998) that was particularly significant for the progress of this research program. In this review, I present definitive evidence that the essential memory trace for eyelid conditioning is localized to the cerebellum and to no other part of the essential circuit, using electrical stimulation of the pontine nuclei-mossy fibers projecting to the cerebellum as the conditional stimulus (CS; it proved to be a supernormal stimulus resulting in much faster learning than with any peripheral CS) and using an electrical stimulus to the output of the cerebellum as a test, which did not change. Pontine patterns of projection to the cerebellum were confirmed with retrograde labeling techniques. 2013 APA, all rights reserved

Graphene optical modulator

NASA Astrophysics Data System (ADS)

Liu, Ming; Yin, Xiaobo; Wang, Feng; Zhang, Xiang

2011-10-01

Data communications have been growing at a speed even faster than Moore's Law, with a 44-fold increase expected within the next 10 years. Data Transfer on such scale would have to recruit optical communication technology and inspire new designs of light sources, modulators, and photodetectors. An ideal optical modulator will require high modulation speed, small device footprint and large operating bandwidth. Silicon modulators based on free carrier plasma dispersion effect and compound semiconductors utilizing direct bandgap transition have seen rapid improvement over the past decade. One of the key limitations for using silicon as modulator material is its weak refractive index change, which limits the footprint of silicon Mach-Zehnder interferometer modulators to millimeters. Other approaches such as silicon microring modulators reduce the operation wavelength range to around 100 pm and are highly sensitive to typical fabrication tolerances and temperature fluctuations. Growing large, high quality wafers of compound semiconductors, and integrating them on silicon or other substrates is expensive, which also restricts their commercialization. In this work, we demonstrate that graphene can be used as the active media for electroabsorption modulators. By tuning the Fermi energy level of the graphene layer, we induced changes in the absorption coefficient of graphene at communication wavelength and achieve a modulation depth above 3 dB. This integrated device also has the potential of working at high speed.

Popeye domain containing proteins are essential for stress-mediated modulation of cardiac pacemaking in mice

PubMed Central

Froese, Alexander; Breher, Stephanie S.; Waldeyer, Christoph; Schindler, Roland F.R.; Nikolaev, Viacheslav O.; Rinné, Susanne; Wischmeyer, Erhard; Schlueter, Jan; Becher, Jan; Simrick, Subreena; Vauti, Franz; Kuhtz, Juliane; Meister, Patrick; Kreissl, Sonja; Torlopp, Angela; Liebig, Sonja K.; Laakmann, Sandra; Müller, Thomas D.; Neumann, Joachim; Stieber, Juliane; Ludwig, Andreas; Maier, Sebastian K.; Decher, Niels; Arnold, Hans-Henning; Kirchhof, Paulus; Fabritz, Larissa; Brand, Thomas

2012-01-01

Cardiac pacemaker cells create rhythmic pulses that control heart rate; pacemaker dysfunction is a prevalent disorder in the elderly, but little is known about the underlying molecular causes. Popeye domain containing (Popdc) genes encode membrane proteins with high expression levels in cardiac myocytes and specifically in the cardiac pacemaking and conduction system. Here, we report the phenotypic analysis of mice deficient in Popdc1 or Popdc2. ECG analysis revealed severe sinus node dysfunction when freely roaming mutant animals were subjected to physical or mental stress. In both mutants, bradyarrhythmia developed in an age-dependent manner. Furthermore, we found that the conserved Popeye domain functioned as a high-affinity cAMP-binding site. Popdc proteins interacted with the potassium channel TREK-1, which led to increased cell surface expression and enhanced current density, both of which were negatively modulated by cAMP. These data indicate that Popdc proteins have an important regulatory function in heart rate dynamics that is mediated, at least in part, through cAMP binding. Mice with mutant Popdc1 and Popdc2 alleles are therefore useful models for the dissection of the mechanisms causing pacemaker dysfunction and could aid in the development of strategies for therapeutic intervention. PMID:22354168

Ethanol-induced oxidant stress modulates hepatic autophagy and proteasome activity

PubMed Central

Donohue, Jr., Terrence M.; Thomes, Paul G.

2014-01-01

In this review, we describe research findings on the effects of alcohol exposure on two major catabolic systems in liver cells: the ubiquitin–proteasome system (UPS) and autophagy. These hydrolytic systems are not unique to liver cells; they exist in all eukaryotic tissues and cells. However, because the liver is the principal site of ethanol metabolism, it sustains the greatest damage from heavy drinking. Thus, the focus of this review is to specifically describe how ethanol oxidation modulates the activities of the UPS and autophagy and the mechanisms by which these changes contribute to the pathogenesis of alcohol-induced liver injury. Here, we describe the history and the importance of cellular hydrolytic systems, followed by a description of each catabolic pathway and the differential modulation of each by ethanol exposure. Overall, the evidence for an involvement of these catabolic systems in the pathogenesis of alcoholic liver disease is quite strong. It underscores their importance, not only as effective means of cellular recycling and eventual energy generation, but also as essential components of cellular defense. PMID:25462063

Essential oil of clove (Eugenia caryophyllata) augments the humoral immune response but decreases cell mediated immunity.

PubMed

Halder, Sumita; Mehta, Ashish K; Mediratta, Pramod K; Sharma, Krishna K

2011-08-01

The present study was undertaken to explore the effect of the essential oil isolated from the buds of Eugenia caryophyllata on some immunological parameters. Humoral immunity was assessed by measuring the hemagglutination titre to sheep red blood cells and delayed type hypersensitivity was assessed by measuring foot pad thickness. Clove oil administration produced a significant increase in the primary as well as secondary humoral immune response. In addition, it also produced a significant decrease in foot pad thickness compared with the control group. Thus, these results suggest that clove oil can modulate the immune response by augmenting humoral immunity and decreasing cell mediated immunity. Copyright © 2011 John Wiley & Sons, Ltd.

An auto-bias control scheme for IQ-modulator with various modulation formats

NASA Astrophysics Data System (ADS)

Zhang, Wenqi; Yuan, Xueguang; Zhang, Yang'an

2016-10-01

We propose and demonstrate an auto-bias control scheme for the IQ-modulator of a flexible optical PSK or QAM or other modulation formats transmitter in this paper. Due to IQ-modulators usually producing higher-order modulation format, these modulation formats involve phase mostly. It is based on that the bias drift will change the operating point and result in varying the output optical phase. This technology has no restrictions on modulation formats, so it has good flexibility. The experimental result show the three biases can be stabilized when the proposed scheme is implemented.

View of docked Apollo 9 Command/Service Module and Lunar Module

NASA Image and Video Library

1969-03-06

AS09-20-3064 (6 March 1969) --- Excellent view of the docked Apollo 9 Command and Service Modules (CSM) and Lunar Module (LM), with Earth in the background, during astronaut David R. Scott's stand-up extravehicular activity (EVA), on the fourth day of the Apollo 9 Earth-orbital mission. Scott, command module pilot, is standing in the open hatch of the Command Module (CM). Astronaut Russell L. Schweickart, lunar module pilot, took this photograph of Scott from the porch of the LM. Inside the LM was astronaut James A. McDivitt, Apollo 9 commander.

Lunar Module 4 moved for mating with Lunar Module Adapter at KSC

NASA Technical Reports Server (NTRS)

1969-01-01

Lunar Module 4 in the Kennedy Space Center's Manned Spacecraft Operations Bldg being moved into position for mating with Spacecraft Lunar Module Adapter (SLA) 13 (17809);Lunar Module 4 being moved for mating with the Spacecraft Lunar Module Adapter in the Kennedy Space Center's (KSC) Manned Spacecraft Operations Building. Lunar module 4 will be flown on the Apollo 10 (Spacecraft 106/Saturn 505) lunar orbit mission (17810).

A Hop-Sensitive Mechanism to Establish Route Optimization in Mobile Networks

NASA Astrophysics Data System (ADS)

Gnanaraj, J. Isac; Newton, P. Calduwel; Arockiam, L.; Kim, Tai-Hoon

The mobile network plays a vital role in mobile communications. It supports both host mobility and network mobility. The mobile network which supports network mobility can be called as NEMO. The NEMO refers to NEtwork MObility or mobile network that moves. Though NEMO provides many supports, it also suffers due to Quality of Service (QoS) issues. One such issue is Route Optimization (RO). When a Mobile Node (MN) is away from Home Network (HN), it will send a binding update to Home Agent (HA) in HN to inform its movement. If the Correspondent Node (CN) wants to send data to MN, it will send data through HA. In this scenario, three networks such as HN, Foreign Network (FN) and Correspondent Network are involved in data transfer. The involvement of these three networks affects the QoS. This paper concentrates on some of the QoS parameters to propose a QoS mechanism to establish RO among these three networks and significantly increases performance of the mobile network.

The C-module-binding factor supports amplification of TRE5-A retrotransposons in the Dictyostelium discoideum genome.

PubMed

Bilzer, Annika; Dölz, Heike; Reinhardt, Alexander; Schmith, Anika; Siol, Oliver; Winckler, Thomas

2011-01-01

Retrotransposable elements are molecular parasites that have invaded the genomes of virtually all organisms. Although retrotransposons encode essential proteins to mediate their amplification, they also require assistance by host cell-encoded machineries that perform functions such as DNA transcription and repair. The retrotransposon TRE5-A of the social amoeba Dictyostelium discoideum generates a notable amount of both sense and antisense RNAs, which are generated from element-internal promoters, located in the A module and the C module, respectively. We observed that TRE5-A retrotransposons depend on the C-module-binding factor (CbfA) to maintain high steady-state levels of TRE5-A transcripts and that CbfA supports the retrotransposition activity of TRE5-A elements. The carboxy-terminal domain of CbfA was found to be required and sufficient to mediate the accumulation of TRE5-A transcripts, but it did not support productive retrotransposition of TRE5-A. This result suggests different roles for CbfA protein domains in the regulation of TRE5-A retrotransposition frequency in D. discoideum cells. Although CbfA binds to the C module in vitro, the factor regulates neither C-module nor A-module promoter activity in vivo. We speculate that CbfA supports the amplification of TRE5-A retrotransposons by suppressing the expression of an as yet unidentified component of the cellular posttranscriptional gene silencing machinery.

Essential oils: from extraction to encapsulation.

PubMed

El Asbahani, A; Miladi, K; Badri, W; Sala, M; Aït Addi, E H; Casabianca, H; El Mousadik, A; Hartmann, D; Jilale, A; Renaud, F N R; Elaissari, A

2015-04-10

Essential oils are natural products which have many interesting applications. Extraction of essential oils from plants is performed by classical and innovative methods. Numerous encapsulation processes have been developed and reported in the literature in order to encapsulate biomolecules, active molecules, nanocrystals, oils and also essential oils for various applications such as in vitro diagnosis, therapy, cosmetic, textile, food etc. Essential oils encapsulation led to numerous new formulations with new applications. This insures the protection of the fragile oil and controlled release. The most commonly prepared carriers are polymer particles, liposomes and solid lipid nanoparticles. Copyright © 2015 Elsevier B.V. All rights reserved.

MAPK-mediated regulation of growth and essential oil composition in a salt-tolerant peppermint (Mentha piperita L.) under NaCl stress.

PubMed

Li, Zhe; Wang, Wenwen; Li, Guilong; Guo, Kai; Harvey, Paul; Chen, Quan; Zhao, Zhongjuan; Wei, Yanli; Li, Jishun; Yang, Hetong

2016-11-01

Peppermint (Mentha × piperita L.) is an important and commonly used flavoring agent worldwide, and salinity is a major stress that limits plant growth and reduces crop productivity. This work demonstrated the metabolic responses of essential oil production including the yield and component composition, gene expression, enzyme activity, and protein activation in a salt-tolerant peppermint Keyuan-1 with respect to NaCl stress. Our results showed that Keyuan-1 maintained normal growth and kept higher yield and content of essential oils under NaCl stress than wild-type (WT) peppermint.Gas chromatography-mass spectrometry (GC-MS) and qPCR results showed that compared to WT seedlings, a 150-mM NaCl stress exerted no obvious changes in essential oil composition, transcriptional level of enzymes related to essential oil metabolism, and activity of pulegone reductase (Pr) in Keyuan-1 peppermint which preserved the higher amount of menthol and menthone as well as the lower content of menthofuran upon the 150-mM NaCl stress. Furthermore, it was noticed that a mitogen-activated protein kinase (MAPK) protein exhibited a time-dependent activation in the Keyuan-1 peppermint and primarily involved in the modulation of the essential oil metabolism in the transcript and enzyme levels during the 12-day treatment of 150 mM NaCl. In all, our data elucidated the effect of NaCl on metabolic responses of essential oil production, and demonstrated the MAPK-dependent regulation mechanism of essential oil biosynthesis in the salt-tolerant peppermint, providing scientific basis for the economic and ecological utilization of peppermint in saline land.

Development and performance of pulse-width-modulated static inverter and converter modules

NASA Technical Reports Server (NTRS)

Pittman, P. F.; Gourash, F.; Birchenough, A. G.; Pittman, P. F.; Ravas, R. J.; Hall, W. G.

1971-01-01

Pulse-width-modulated inverter and converter modules are being developed for modular aerospace electrical power systems. The modules, rate 2.5 kilowatts per module and 10-minute - 150-percent overload, operate from 56 volts dc. The converter module provides two output voltages: a nominal link voltage of 200 volts dc when used with the inverter, and 150 volts dc to a load bus when used separately. The inverter module output is 400-hertz, sinusoidal, three-phase, 120/208 volts. Tests of breadboard models with standard parts and integrated circuits show rated power efficiencies of 71.4 and 85.1 percent and voltage regulation of 5 and 3.1 percent for inverter and converter modules, respectively. Sine-wave output distortion is 0.74 percent.

RTI Essential Components Integrity Rubric

ERIC Educational Resources Information Center

National Center on Response to Intervention, 2011

2011-01-01

The Response to Intervention (RTI) Essential Components Integrity Rubric is for use by individuals who are responsible for monitoring school-level fidelity of RTI implementation. The rubric is aligned with "Essential Components of RTI: A Closer Look at Response to Intervention" (National Center on Response to Intervention, 2010).…

Antimicrobial and Antibiofilm Activity and Machine Learning Classification Analysis of Essential Oils from Different Mediterranean Plants against Pseudomonas aeruginosa.

PubMed

Artini, Marco; Patsilinakos, Alexandros; Papa, Rosanna; Božović, Mijat; Sabatino, Manuela; Garzoli, Stefania; Vrenna, Gianluca; Tilotta, Marco; Pepi, Federico; Ragno, Rino; Selan, Laura

2018-02-23

Pseudomonas aeruginosa is a ubiquitous organism and opportunistic pathogen that can cause persistent infections due to its peculiar antibiotic resistance mechanisms and to its ability to adhere and form biofilm. The interest in the development of new approaches for the prevention and treatment of biofilm formation has recently increased. The aim of this study was to seek new non-biocidal agents able to inhibit biofilm formation, in order to counteract virulence rather than bacterial growth and avoid the selection of escape mutants. Herein, different essential oils extracted from Mediterranean plants were analyzed for their activity against P. aeruginosa . Results show that they were able to destabilize biofilm at very low concentration without impairing bacterial viability. Since the action is not related to a bacteriostatic/bactericidal activity on P. aeruginosa , the biofilm change of growth in presence of the essential oils was possibly due to a modulation of the phenotype. To this aim, application of machine learning algorithms led to the development of quantitative activity-composition relationships classification models that allowed to direct point out those essential oil chemical components more involved in the inhibition of biofilm production. The action of selected essential oils on sessile phenotype make them particularly interesting for possible applications such as prevention of bacterial contamination in the community and in healthcare environments in order to prevent human infections. We assayed 89 samples of different essential oils as P. aeruginosa anti-biofilm. Many samples inhibited P. aeruginosa biofilm at concentrations as low as 48.8 µg/mL. Classification of the models was developed through machine learning algorithms.

Opiates Modulate Noxious Chemical Nociception through a Complex Monoaminergic/Peptidergic Cascade

PubMed Central

Mills, Holly; Ortega, Amanda; Law, Wenjing; Hapiak, Vera; Summers, Philip; Clark, Tobias

2016-01-01

The ability to detect noxious stimuli, process the nociceptive signal, and elicit an appropriate behavioral response is essential for survival. In Caenorhabditis elegans, opioid receptor agonists, such as morphine, mimic serotonin, and suppress the overall withdrawal from noxious stimuli through a pathway requiring the opioid-like receptor, NPR-17. This serotonin- or morphine-dependent modulation can be rescued in npr-17-null animals by the expression of npr-17 or a human κ opioid receptor in the two ASI sensory neurons, with ASI opioid signaling selectively inhibiting ASI neuropeptide release. Serotonergic modulation requires peptides encoded by both nlp-3 and nlp-24, and either nlp-3 or nlp-24 overexpression mimics morphine and suppresses withdrawal. Peptides encoded by nlp-3 act differentially, with only NLP-3.3 mimicking morphine, whereas other nlp-3 peptides antagonize NLP-3.3 modulation. Together, these results demonstrate that opiates modulate nociception in Caenorhabditis elegans through a complex monoaminergic/peptidergic cascade, and suggest that this model may be useful for dissecting opiate signaling in mammals. SIGNIFICANCE STATEMENT Opiates are used extensively to treat chronic pain. In Caenorhabditis elegans, opioid receptor agonists suppress the overall withdrawal from noxious chemical stimuli through a pathway requiring an opioid-like receptor and two distinct neuropeptide-encoding genes, with individual peptides from the same gene functioning antagonistically to modulate nociception. Endogenous opioid signaling functions as part of a complex, monoaminergic/peptidergic signaling cascade and appears to selectively inhibit neuropeptide release, mediated by a α-adrenergic-like receptor, from two sensory neurons. Importantly, receptor null animals can be rescued by the expression of the human κ opioid receptor, and injection of human opioid receptor ligands mimics exogenous opiates, highlighting the utility of this model for dissecting opiate

Efficient Modulation of γ-Aminobutyric Acid Type A Receptors by Piperine Derivatives

PubMed Central

2014-01-01

Piperine activates TRPV1 (transient receptor potential vanilloid type 1 receptor) receptors and modulates γ-aminobutyric acid type A receptors (GABAAR). We have synthesized a library of 76 piperine analogues and analyzed their effects on GABAAR by means of a two-microelectrode voltage-clamp technique. GABAAR were expressed in Xenopus laevis oocytes. Structure–activity relationships (SARs) were established to identify structural elements essential for efficiency and potency. Efficiency of piperine derivatives was significantly increased by exchanging the piperidine moiety with either N,N-dipropyl, N,N-diisopropyl, N,N-dibutyl, p-methylpiperidine, or N,N-bis(trifluoroethyl) groups. Potency was enhanced by replacing the piperidine moiety by N,N-dibutyl, N,N-diisobutyl, or N,N-bistrifluoroethyl groups. Linker modifications did not substantially enhance the effect on GABAAR. Compound 23 [(2E,4E)-5-(1,3-benzodioxol-5-yl)-N,N-dipropyl-2,4-pentadienamide] induced the strongest modulation of GABAA (maximal GABA-induced chloride current modulation (IGABA-max = 1673% ± 146%, EC50 = 51.7 ± 9.5 μM), while 25 [(2E,4E)-5-(1,3-benzodioxol-5-yl)-N,N-dibutyl-2,4-pentadienamide] displayed the highest potency (EC50 = 13.8 ± 1.8 μM, IGABA-max = 760% ± 47%). Compound 23 induced significantly stronger anxiolysis in mice than piperine and thus may serve as a starting point for developing novel GABAAR modulators. PMID:24905252

Physics of frequency-modulated comb generation in quantum-well diode lasers

NASA Astrophysics Data System (ADS)

Dong, Mark; Cundiff, Steven T.; Winful, Herbert G.

2018-05-01

We investigate the physical origin of frequency-modulated combs generated from single-section semiconductor diode lasers based on quantum wells, isolating the essential physics necessary for comb generation. We find that the two effects necessary for comb generation—spatial hole burning (leading to multimode operation) and four-wave mixing (leading to phase locking)—are indeed present in some quantum-well systems. The physics of comb generation in quantum wells is similar to that in quantum dot and quantum cascade lasers. We discuss the nature of the spectral phase and some important material parameters of these diode lasers.

How electrostatic networks modulate specificity and stability of collagen.

PubMed

Zheng, Hongning; Lu, Cheng; Lan, Jun; Fan, Shilong; Nanda, Vikas; Xu, Fei

2018-06-12

One-quarter of the 28 types of natural collagen exist as heterotrimers. The oligomerization state of collagen affects the structure and mechanics of the extracellular matrix, providing essential cues to modulate biological and pathological processes. A lack of high-resolution structural information limits our mechanistic understanding of collagen heterospecific self-assembly. Here, the 1.77-Å resolution structure of a synthetic heterotrimer demonstrates the balance of intermolecular electrostatics and hydrogen bonding that affects collagen stability and heterospecificity of assembly. Atomistic simulations and mutagenesis based on the solved structure are used to explore the contributions of specific interactions to energetics. A predictive model of collagen stability and specificity is developed for engineering novel collagen structures.

Brg1 modulates enhancer activation in mesoderm lineage commitment

DOE PAGES

Alexander, Jeffrey M.; Hota, Swetansu K.; He, Daniel; ...

2015-03-26

The interplay between different levels of gene regulation in modulating developmental transcriptional programs, such as histone modifications and chromatin remodeling, is not well understood. Here, we show that the chromatin remodeling factor Brg1 is required for enhancer activation in mesoderm induction. In an embryonic stem cell-based directed differentiation assay, the absence of Brg1 results in a failure of cardiomyocyte differentiation and broad deregulation of lineage-specific gene expression during mesoderm induction. We find that Brg1 co-localizes with H3K27ac at distal enhancers and is required for robust H3K27 acetylation at distal enhancers that are activated during mesoderm induction. Brg1 is also requiredmore » to maintain Polycomb-mediated repression of non-mesodermal developmental regulators, suggesting cooperativity between Brg1 and Polycomb complexes. Thus, Brg1 is essential for modulating active and repressive chromatin states during mesoderm lineage commitment, in particular the activation of developmentally important enhancers. In conclusion, these findings demonstrate interplay between chromatin remodeling complexes and histone modifications that, together, ensure robust and broad gene regulation during crucial lineage commitment decisions.« less

Standardization of the energy performance of photovoltaic modules in real operating conditions

NASA Astrophysics Data System (ADS)

Viganó, Davide; Kenny, Robert P.; Müllejans, Harald; Alimonti, Gianluca

2014-12-01

The performance of a PV module at STC [1] is a useful indicator for comparing the peak performance of different module types, but on its own is not sufficient to accurately predict how much energy a module will deliver in the field when subjected to a wide range of real operating conditions [2]. An Energy Rating approach has to be preferred for that aim. It is currently under development the standard series IEC 61853 on Energy Rating, for which only part 1 [3] has been issued. It describes methods to characterize the module performance as a function of irradiance and temperature. The reproducibility of the power matrix measurements obtained by the three different methods specified in the standard, namely: under natural sunlight using a tracking system; under natural sunlight without tracker; and a large area pulsed solar simulator of Class AAA were evaluated and discussed [4,5]. The work here presented is focused on the second method listed above, which explores the real working conditions for a PV device and therefore it represents the situation where Energy Rating procedures are expected to give the largest deviations from the STC predictions. The system for continuous monitoring of module performances, already implemented at ESTI, has been recently replaced with a new system having a number of improvements described in the following. The two system results have been compared showing a discrete compatibility. The two power matrices are then merged together using a weighted average and compared to those acquired with the other two remaining "ideal" systems. An interesting tendency seems to come up from this comparison, making the power rating under real operating conditions an essential procedure for energy rating purposes.

Integrin-linked Kinase Interactions with ELMO2 Modulate Cell Polarity

PubMed Central

Ho, Ernest; Irvine, Tames; Vilk, Gregory J.A.; Lajoie, Gilles; Ravichandran, Kodi S.; D'Souza, Sudhir J.A.

2009-01-01

Cell polarization is a key prerequisite for directed migration during development, tissue regeneration, and metastasis. Integrin-linked kinase (ILK) is a scaffold protein essential for cell polarization, but very little is known about the precise mechanisms whereby ILK modulates polarization in normal epithelia. Elucidating these mechanisms is essential to understand tissue morphogenesis, transformation, and repair. Here we identify a novel ILK protein complex that includes Engulfment and Cell Motility 2 (ELMO2). We also demonstrate the presence of RhoG in ILK–ELMO2 complexes, and the localization of this multiprotein species specifically to the leading lamellipodia of polarized cells. Significantly, the ability of RhoG to bind ELMO is crucial for ILK induction of cell polarization, and the joint expression of ILK and ELMO2 synergistically promotes the induction of front-rear polarity and haptotactic migration. This places RhoG–ELMO2–ILK complexes in a key position for the development of cell polarity and forward movement. Although ILK is a component of many diverse multiprotein species that may contribute to cell polarization, expression of dominant-negative ELMO2 mutants is sufficient to abolish the ability of ILK to promote cell polarization. Thus, its interaction with ELMO2 and RhoG is essential for the ability of ILK to induce front-rear cell polarity. PMID:19439446

Intracellular signal modulation by nanomaterials.

PubMed

Hussain, Salik; Garantziotis, Stavros; Rodrigues-Lima, Fernando; Dupret, Jean-Marie; Baeza-Squiban, Armelle; Boland, Sonja

2014-01-01

A thorough understanding of the interactions of nanomaterials with biological systems and the resulting activation of signal transduction pathways is essential for the development of safe and consumer friendly nanotechnology. Here we present an overview of signaling pathways induced by nanomaterial exposures and describe the possible correlation of their physicochemical characteristics with biological outcomes. In addition to the hierarchical oxidative stress model and a review of the intrinsic and cell-mediated mechanisms of reactive oxygen species (ROS) generating capacities of nanomaterials, we also discuss other oxidative stress dependent and independent cellular signaling pathways. Induction of the inflammasome, calcium signaling, and endoplasmic reticulum stress are reviewed. Furthermore, the uptake mechanisms can be of crucial importance for the cytotoxicity of nanomaterials and membrane-dependent signaling pathways have also been shown to be responsible for cellular effects of nanomaterials. Epigenetic regulation by nanomaterials, effects of nanoparticle-protein interactions on cell signaling pathways, and the induction of various cell death modalities by nanomaterials are described. We describe the common trigger mechanisms shared by various nanomaterials to induce cell death pathways and describe the interplay of different modalities in orchestrating the final outcome after nanomaterial exposures. A better understanding of signal modulations induced by nanomaterials is not only essential for the synthesis and design of safer nanomaterials but will also help to discover potential nanomedical applications of these materials. Several biomedical applications based on the different signaling pathways induced by nanomaterials are already proposed and will certainly gain a great deal of attraction in the near future.

Weakly Coretractable Modules

NASA Astrophysics Data System (ADS)

Hadi, Inaam M. A.; Al-aeashi, Shukur N.

2018-05-01

If R is a ring with identity and M is a unitary right R-module. Here we introduce the class of weakly coretractable module. Some basic properties are investigated and some relationships between these modules and other related one are introduced.

Abscisic acid accumulation modulates auxin transport in the root tip to enhance proton secretion for maintaining root growth under moderate water stress.

PubMed

Xu, Weifeng; Jia, Liguo; Shi, Weiming; Liang, Jiansheng; Zhou, Feng; Li, Qianfeng; Zhang, Jianhua

2013-01-01

Maintenance of root growth is essential for plant adaptation to soil drying. Here, we tested the hypothesis that auxin transport is involved in mediating ABA's modulation by activating proton secretion in the root tip to maintain root growth under moderate water stress. Rice and Arabidopsis plants were raised under a hydroponic system and subjected to moderate water stress (-0.47 MPa) with polyethylene glycol (PEG). ABA accumulation, auxin transport and plasma membrane H(+)-ATPase activity at the root tip were monitored in addition to the primary root elongation and root hair density. We found that moderate water stress increases ABA accumulation and auxin transport in the root apex. Additionally, ABA modulation is involved in the regulation of auxin transport in the root tip. The transported auxin activates the plasma membrane H(+)-ATPase to release more protons along the root tip in its adaption to moderate water stress. The proton secretion in the root tip is essential in maintaining or promoting primary root elongation and root hair development under moderate water stress. These results suggest that ABA accumulation modulates auxin transport in the root tip, which enhances proton secretion for maintaining root growth under moderate water stress. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

Developing Essential Understanding of Rational Numbers for Teaching Mathematics in Grades 3-5. Essential Understandings

ERIC Educational Resources Information Center

Clarke, Carne; Fisher, William; Marks, Rick; Ross, Sharon; Zbiek, Rose Mary

2010-01-01

This book focuses on essential knowledge for teachers about rational numbers. It is organized around four big ideas, supported by multiple smaller, interconnected ideas--essential understandings. Taking teachers beyond a simple introduction to rational numbers, the book will broaden and deepen their mathematical understanding of one of the most…

[Essentialism and typological thinking in biological systematics].

PubMed

Vasil'eva, L N

2003-01-01

In biological literature, essentialism and typological thinking are believed to be incompatible with evolutionary ideas. At present, the same considerations underlay the claims to abandon the Linnaean hierarchy, or the fundamental classificatory structure rooted in essentialism. This paper suggests to reconsider the negative views of Plato's typology and Aristotle's essentialism following the narrow interpretations that have nothing to do with the classification of living beings. Plato's theory of 'ideas' (or 'forms') is the basis of classificatory theory; it provided such concepts as 'species', 'genus', 'essence', 'dichotomous division' but the development of this theory in the framework of moral and esthetic values could not be beneficial to biology. Aristotle's essentialism is more complicated and exists in two forms; one of these, or classificatory essentialism, is a modification of Plato's typology; another one, or organismal essentialism, represents the shift of 'essence' from the world of relations between objects to the realm of particular things, where the concept of essence lost its basic meaning. It is senseless to look for unreal 'type of an organism' ('essence of a thing') but precisely this kind of essentialism is attractive for biologists and philosophers. Organismal essentialism is the underlying basis of so-called 'individuality thesis' that is used as a weapon against classificatory essentialism. The same thesis is associated with an extensional vision of taxa that also explains the criticism of Linnaean hierarchy, while the latter is the intentional structure and the first tool suggested for the rank coordination of many unequal taxa.

Enhanced modulation rates via field modulation in spin torque nano-oscillators

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

Purbawati, A.; Garcia-Sanchez, F.; Buda-Prejbeanu, L. D.

Spin Transfer Nano-Oscillators (STNOs) are promising candidates for telecommunications applications due to their frequency tuning capabilities via either a dc current or an applied field. This frequency tuning is of interest for Frequency Shift Keying concepts to be used in wireless communication schemes or in read head applications. For these technological applications, one important parameter is the characterization of the maximum achievable rate at which an STNO can respond to a modulating signal, such as current or field. Previous studies of in-plane magnetized STNOs on frequency modulation via an rf current revealed that the maximum achievable rate is limited bymore » the amplitude relaxation rate Γ{sub p}, which gives the time scale over which amplitude fluctuations are damped out. This might be a limitation for applications. Here, we demonstrate via numerical simulation that application of an additional rf field is an alternative way for modulation of the in-plane magnetized STNO configuration, which has the advantage that frequency modulation is not limited by the amplitude relaxation rate, so that higher modulation rates above GHz are achievable. This occurs when the modulating rf field is oriented along the easy axis (longitudinal rf field). Tilting the direction of the modulating rf field in-plane and perpendicularly with respect to the easy axis (transverse rf field), the modulation is again limited by the amplitude relaxation rate similar to the response observed in current modulation.« less

Chemosensation of Bacterial Secondary Metabolites Modulates Neuroendocrine Signaling and Behavior of C. elegans

PubMed Central

Meisel, Joshua D.; Panda, Oishika; Mahanti, Parag; Schroeder, Frank C.; Kim, Dennis H.

2014-01-01

Summary Discrimination among pathogenic and beneficial microbes is essential for host organism immunity and homeostasis. Here, we show that chemosensory detection of two secondary metabolites produced by Pseudomonas aeruginosa modulates a neuroendocrine signaling pathway that promotes avoidance behavior in the simple animal host Caenorhabditis elegans. Secondary metabolites phenazine-1-carboxamide and pyochelin activate a G protein-signaling pathway in the ASJ chemosensory neuron pair that induces expression of the neuromodulator DAF-7/TGF-β. DAF-7, in turn, activates a canonical TGF-β signaling pathway in adjacent interneurons to modulate aerotaxis behavior and promote avoidance of pathogenic P. aeruginosa. Our data provide a chemical, genetic, and neuronal basis for how the behavior and physiology of a simple animal host can be modified by the microbial environment, and suggest that secondary metabolites produced by microbes may provide environmental cues that contribute to pathogen recognition and host survival. PMID:25303524

Modulated grayscale UV pattern for uniform photopolymerization based on a digital micromirror device system

NASA Astrophysics Data System (ADS)

Yoon, Jinsik; Kim, Kibeom; Park, Wook

2017-07-01

We present an essential method for generating microparticles uniformly in a single ultraviolet (UV) light exposure area for optofluidic maskless lithography. In the optofluidic maskless lithography process, the productivity of monodisperse microparticles depends on the size of the UV exposure area. An effective fabrication area is determined by the size of the UV intensity profile map, satisfying the required uniformity of UV intensity. To increase the productivity of monodisperse microparticles in optofluidic maskless lithography, we expanded the effective UV exposure area by modulating the intensity of the desired UV light pattern based on the premeasured UV intensity profile map. We verified the improvement of the uniformity of the microparticles generated by the proposed modulation technique, providing histogram analyses of the conjugated fluorescent intensities and the sizes of the microparticles. Additionally, we demonstrated the generation of DNA uniformly encapsulated in microparticles.

A positive feedback at the cellular level promotes robustness and modulation at the circuit level

PubMed Central

Dethier, Julie; Drion, Guillaume; Franci, Alessio

2015-01-01

This article highlights the role of a positive feedback gating mechanism at the cellular level in the robustness and modulation properties of rhythmic activities at the circuit level. The results are presented in the context of half-center oscillators, which are simple rhythmic circuits composed of two reciprocally connected inhibitory neuronal populations. Specifically, we focus on rhythms that rely on a particular excitability property, the postinhibitory rebound, an intrinsic cellular property that elicits transient membrane depolarization when released from hyperpolarization. Two distinct ionic currents can evoke this transient depolarization: a hyperpolarization-activated cation current and a low-threshold T-type calcium current. The presence of a slow activation is specific to the T-type calcium current and provides a slow positive feedback at the cellular level that is absent in the cation current. We show that this slow positive feedback is required to endow the network rhythm with physiological modulation and robustness properties. This study thereby identifies an essential cellular property to be retained at the network level in modeling network robustness and modulation. PMID:26311181

Studies on Modulation of Gut Microbiota by Wine Polyphenols: From Isolated Cultures to Omic Approaches

PubMed Central

Dueñas, Montserrat; Cueva, Carolina; Muñoz-González, Irene; Jiménez-Girón, Ana; Sánchez-Patán, Fernando; Santos-Buelga, Celestino; Moreno-Arribas, M. Victoria; Bartolomé, Begoña

2015-01-01

Moderate consumption of wine seems to produce positive health effects derived from the occurrence of bioactive polyphenols. The gut microbiota is involved in the metabolism of phenolic compounds, and these compounds and/or their metabolites may modulate gut microbiota through the stimulation of the growth of beneficial bacteria and the inhibition of pathogenic bacteria. The characterization of bacterial metabolites derived from polyphenols is essential in order to understand their effects, including microbial modulation, and therefore to associate dietary intake with particular health effects. This review aims to summarize the current information about the two-way “wine polyphenols–gut microbiota” interaction, from a perspective based on the experimental and analytical designs used. The availability of advanced methods for monitoring bacterial communities, along with the combination of in vitro and in vivo models, could help to assess the metabolism of polyphenols in the human body and to monitor total bacterial communities, and, therefore, to elucidate the implications of diet on the modulation of microbiota for delivering health benefits. PMID:26785335

Architectured Materials to Improve the Reliability of Power Electronics Modules: Substrate and Lead-Free Solder

NASA Astrophysics Data System (ADS)

Kaabi, Abderrahmen; Bienvenu, Yves; Ryckelynck, David; Pierre, Bertrand

2014-03-01

Power electronics modules (>100 A, >500 V) are essential components for the development of electrical and hybrid vehicles. These modules are formed from silicon chips (transistors and diodes) assembled on copper substrates by soldering. Owing to the fact that the assembly is heterogeneous, and because of thermal gradients, shear stresses are generated in the solders and cause premature damage to such electronics modules. This work focuses on architectured materials for the substrate and on lead-free solders to reduce the mechanical effects of differential expansion, improve the reliability of the assembly, and achieve a suitable operating temperature (<175°C). These materials are composites whose thermomechanical properties have been optimized by numerical simulation and validated experimentally. The substrates have good thermal conductivity (>280 W m-1 K-1) and a macroscopic coefficient of thermal expansion intermediate between those of Cu and Si, as well as limited structural evolution in service conditions. An approach combining design, optimization, and manufacturing of new materials has been followed in this study, leading to improved thermal cycling behavior of the component.

Robust and Cost-Efficient Communication Based on SNMP in Mobile Networks

NASA Astrophysics Data System (ADS)

Ryu, Sang-Hoon; Baik, Doo-Kwon

A main challenge in the design of this mobile network is the development of dynamic routing protocols that can efficiently find routes between two communicating nodes. Multimedia streaming services are receiving considerable interest in the mobile network business. An entire mobile network may change its point of attachment to the Internet. The mobile network is operated by a basic specification to support network mobility called Network Mobility (NEMO) Basic Support. However, NEMO basic Support mechanism has some problem in continuous communication. In this paper, we propose robust and cost-efficient algorithm. And we simulate proposed method and conclude some remarks.

Essential Medicines in National Constitutions

PubMed Central

Toebes, Brigit; Hogerzeil, Hans

2016-01-01

Abstract A constitutional guarantee of access to essential medicines has been identified as an important indicator of government commitment to the progressive realization of the right to the highest attainable standard of health. The objective of this study was to evaluate provisions on access to essential medicines in national constitutions, to identify comprehensive examples of constitutional text on medicines that can be used as a model for other countries, and to evaluate the evolution of constitutional medicines-related rights since 2008. Relevant articles were selected from an inventory of constitutional texts from WHO member states. References to states’ legal obligations under international human rights law were evaluated. Twenty-two constitutions worldwide now oblige governments to protect and/or to fulfill accessibility of, availability of, and/or quality of medicines. Since 2008, state responsibilities to fulfill access to essential medicines have expanded in five constitutions, been maintained in four constitutions, and have regressed in one constitution. Government commitments to essential medicines are an important foundation of health system equity and are included increasingly in state constitutions. PMID:27781006

Essential Questions

ERIC Educational Resources Information Center

Wilhelm, Jeffrey D.

2012-01-01

The secret to teaching may be as simple as asking students good questions--and then giving them the opportunity to find the answers. The author shares how he uses essential questions that set the class off on an inquiry. Rather than consuming information that he distributes and then repeating it on a test, students carry out their own…

Insights into structure–activity relationship of GABAA receptor modulating coumarins and furanocoumarins

PubMed Central

Singhuber, Judith; Baburin, Igor; Ecker, Gerhard F.; Kopp, Brigitte; Hering, Steffen

2011-01-01

The coumarins imperatorin and osthole are known to exert anticonvulsant activity. We have therefore analyzed the modulation of GABA-induced chloride currents (IGABA) by a selection of 18 coumarin derivatives on recombinant α1β2γ2S GABAA receptors expressed in Xenopus laevis oocytes by means of the two-microelectrode voltage clamp technique. Osthole (EC50=14±1 μM) and oxypeucedanin (EC50=25±8 μM) displayed the highest efficiency with IGABA potentiation of 116±4% and 547±56%, respectively. IGABA enhancement by osthole and oxypeucedanin was not inhibited by flumazenil (1 μM) indicating an interaction with a binding site distinct from the benzodiazepine binding site. In general, prenyl residues are essential for the positive modulatory activity, while longer side chains or bulkier residues (e.g. geranyl residues) diminish IGABA modulation. Generation of a binary classification tree revealed the importance of polarisability, which is sufficient to distinguish actives from inactives. A 4-point pharmacophore model based on oxypeucedanin – comprising three hydrophobic and one aromatic feature – identified 6 out of 7 actives as hits. In summary, (oxy-)prenylated coumarin derivatives from natural origin represent new GABAA receptor modulators. PMID:21749864

Estradiol rapidly modulates spinogenesis in hippocampal dentate gyrus: Involvement of kinase networks.

PubMed

Hojo, Yasushi; Munetomo, Arisa; Mukai, Hideo; Ikeda, Muneki; Sato, Rei; Hatanaka, Yusuke; Murakami, Gen; Komatsuzaki, Yoshimasa; Kimoto, Tetsuya; Kawato, Suguru

2015-08-01

This article is part of a Special Issue "Estradiol and cognition". Estradiol (E2) is locally synthesized within the hippocampus and the gonads. Rapid modulation of hippocampal synaptic plasticity by E2 is essential for synaptic regulation. The molecular mechanisms of modulation through the synaptic estrogen receptor (ER) and its downstream signaling, however, are largely unknown in the dentate gyrus (DG). We investigated the E2-induced modulation of dendritic spines in male adult rat hippocampal slices by imaging Lucifer Yellow-injected DG granule cells. Treatments with 1 nM E2 increased the density of spines by approximately 1.4-fold within 2h. Spine head diameter analysis showed that the density of middle-head spines (0.4-0.5 μm) was significantly increased. The E2-induced spine density increase was suppressed by blocking Erk MAPK, PKA, PKC and LIMK. These suppressive effects by kinase inhibitors are not non-specific ones because the GSK-3β antagonist did not inhibit E2-induced spine increase. The ER antagonist ICI 182,780 also blocked the E2-induced spine increase. Taken together, these results suggest that E2 rapidly increases the density of spines through kinase networks that are driven by synaptic ER. Copyright © 2015 Elsevier Inc. All rights reserved.

Directed network modules

NASA Astrophysics Data System (ADS)

Palla, Gergely; Farkas, Illés J.; Pollner, Péter; Derényi, Imre; Vicsek, Tamás

2007-06-01

A search technique locating network modules, i.e. internally densely connected groups of nodes in directed networks is introduced by extending the clique percolation method originally proposed for undirected networks. After giving a suitable definition for directed modules we investigate their percolation transition in the Erdos-Rényi graph both analytically and numerically. We also analyse four real-world directed networks, including Google's own web-pages, an email network, a word association graph and the transcriptional regulatory network of the yeast Saccharomyces cerevisiae. The obtained directed modules are validated by additional information available for the nodes. We find that directed modules of real-world graphs inherently overlap and the investigated networks can be classified into two major groups in terms of the overlaps between the modules. Accordingly, in the word-association network and Google's web-pages, overlaps are likely to contain in-hubs, whereas the modules in the email and transcriptional regulatory network tend to overlap via out-hubs.

Treatment of essential tremor with arotinolol.

PubMed

Kuroda, Y; Kakigi, R; Shibasaki, H

1988-04-01

We investigated the effect of arotinolol, a new peripherally acting beta-adrenergic blocker, in 15 patients with essential tremor. The patients received 30 mg per day of arotinolol for 8 weeks. Accelerometer readings showed a significant reduction in amplitude of postural tremor after treatment. Action tremor also improved to essentially the same degree as postural tremor. The present findings support the view that the therapeutic effect of beta-blockers in essential tremor is mediated by peripheral beta-adrenergic receptors.

The C-Module-Binding Factor Supports Amplification of TRE5-A Retrotransposons in the Dictyostelium discoideum Genome ▿

PubMed Central

Bilzer, Annika; Dölz, Heike; Reinhardt, Alexander; Schmith, Anika; Siol, Oliver; Winckler, Thomas

2011-01-01

Retrotransposable elements are molecular parasites that have invaded the genomes of virtually all organisms. Although retrotransposons encode essential proteins to mediate their amplification, they also require assistance by host cell-encoded machineries that perform functions such as DNA transcription and repair. The retrotransposon TRE5-A of the social amoeba Dictyostelium discoideum generates a notable amount of both sense and antisense RNAs, which are generated from element-internal promoters, located in the A module and the C module, respectively. We observed that TRE5-A retrotransposons depend on the C-module-binding factor (CbfA) to maintain high steady-state levels of TRE5-A transcripts and that CbfA supports the retrotransposition activity of TRE5-A elements. The carboxy-terminal domain of CbfA was found to be required and sufficient to mediate the accumulation of TRE5-A transcripts, but it did not support productive retrotransposition of TRE5-A. This result suggests different roles for CbfA protein domains in the regulation of TRE5-A retrotransposition frequency in D. discoideum cells. Although CbfA binds to the C module in vitro, the factor regulates neither C-module nor A-module promoter activity in vivo. We speculate that CbfA supports the amplification of TRE5-A retrotransposons by suppressing the expression of an as yet unidentified component of the cellular posttranscriptional gene silencing machinery. PMID:21076008

Teller Training Module: Off-Line Banking System. High-Technology Training Module.

ERIC Educational Resources Information Center

Lund, Candyce J.

This teller training module on offline banking systems is intended to be part of a postsecondary financial applications course. The module contains the following sections: module objective; specific objective; content--electronic audit machine key functions, practice packet--sample bank transactions and practicing procedures, and…

Domain Requirements for DNA Unwinding by Mycobacterial UvrD2, an Essential DNA Helicase†

PubMed Central

Sinha, Krishna Murari; Stephanou, Nicolas C.; Unciuleac, Mihaela-Carmen; Glickman, Michael S.; Shuman, Stewart

2008-01-01

Mycobacterial UvrD2 is a DNA-dependent ATPase with 3′ to 5′ helicase activity. UvrD2 is an atypical helicase, insofar as its N-terminal ATPase domain resembles the superfamily I helicases UvrD/PcrA, yet it has a C-terminal HRDC domain, which is a feature of RecQ-type superfamily II helicases. The ATPase and HRDC domains are connected by a CxxC-(14)-CxxC tetracysteine module that defines a new clade of UvrD2-like bacterial helicases found only in Actinomycetales. By characterizing truncated versions of Mycobacterium smegmatis UvrD2, we show that whereas the HRDC domain is not required for ATPase or helicase activities in vitro, deletion of the tetracysteine module abolishes duplex unwinding while preserving ATP hydrolysis. Replacing each of the CxxC motifs with a double-alanine variant AxxA had no effect on duplex unwinding, signifying that the domain module, not the cysteines, is crucial for function. The helicase activity of a truncated UvrD2 lacking the tetracysteine and HRDC domains was restored by the DNA-binding protein Ku, a component of the mycobacterial NHEJ system and a cofactor for DNA unwinding by the paralogous mycobacterial helicase UvrD1. Our findings indicate that coupling of ATP hydrolysis to duplex unwinding can be achieved by protein domains acting in cis or trans. Attempts to disrupt the M. smegmatis uvrD2 gene were unsuccessful unless a second copy of uvrD2 was present elsewhere in the chromosome, indicating that UvrD2 is essential for growth of M. smegmatis. PMID:18702526

42 CFR 440.347 - Essential health benefits.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 4 2013-10-01 2013-10-01 false Essential health benefits. 440.347 Section 440.347 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES...-Equivalent Coverage § 440.347 Essential health benefits. (a) Alternative Benefit Plans must contain essential...

42 CFR 440.347 - Essential health benefits.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 4 2014-10-01 2014-10-01 false Essential health benefits. 440.347 Section 440.347 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES...-Equivalent Coverage § 440.347 Essential health benefits. (a) Alternative Benefit Plans must contain essential...

Teaching Pain Management in Interprofessional Medical Education: A Review of Three Portal of Geriatric Online Education Modules.

PubMed

Madaus, Stacy M; Lim, Lionel S

2016-10-01

Chronic pain is an international healthcare crisis that affects an estimated 1.5 billion individuals worldwide, but pain management is not emphasized in the medical school curriculum, and thus supplemental education is essential. The Portal of Geriatric Online Education (POGOe) is a free repository of teaching modules for use by geriatric educators and learners. This article highlights three teaching modules available on this site: It's My Old Back Again: An Approach to Diagnosing and Managing Back Pain in the Older Adult (POGOe ID: 21670), Computer Based Learning Workbook, Third Edition module on Pain Management (POGOe ID: 21036), and Aging Q3 Curriculum on Pain Management of Older Adult Patients (POGOe ID: 21187). These modules were chosen based on their ability to address the major topics that the International Association for the Study of Pain proposes should be included in medical school curricula: mulitdimensional nature of pain, pain assessment and measurement, management of pain, and clinical conditions resulting in pain in older adults. They were also selected for their ability to be adapted for interprofessional education and how well they integrate basic science and clinical principles. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

SpecBit, DecayBit and PrecisionBit: GAMBIT modules for computing mass spectra, particle decay rates and precision observables

NASA Astrophysics Data System (ADS)

Athron, Peter; Balázs, Csaba; Dal, Lars A.; Edsjö, Joakim; Farmer, Ben; Gonzalo, Tomás E.; Kvellestad, Anders; McKay, James; Putze, Antje; Rogan, Chris; Scott, Pat; Weniger, Christoph; White, Martin

2018-01-01

We present the GAMBIT modules SpecBit, DecayBit and PrecisionBit. Together they provide a new framework for linking publicly available spectrum generators, decay codes and other precision observable calculations in a physically and statistically consistent manner. This allows users to automatically run various combinations of existing codes as if they are a single package. The modular design allows software packages fulfilling the same role to be exchanged freely at runtime, with the results presented in a common format that can easily be passed to downstream dark matter, collider and flavour codes. These modules constitute an essential part of the broader GAMBIT framework, a major new software package for performing global fits. In this paper we present the observable calculations, data, and likelihood functions implemented in the three modules, as well as the conventions and assumptions used in interfacing them with external codes. We also present 3-BIT-HIT, a command-line utility for computing mass spectra, couplings, decays and precision observables in the MSSM, which shows how the three modules can easily be used independently of GAMBIT.

Receiver bandwidth effects on complex modulation and detection using directly modulated lasers.

PubMed

Yuan, Feng; Che, Di; Shieh, William

2016-05-01

Directly modulated lasers (DMLs) have long been employed for short- and medium-reach optical communications due to their low cost. Recently, a new modulation scheme called complex modulated DMLs has been demonstrated showing a significant optical signal to noise ratio sensitivity enhancement compared with the traditional intensity-only detection scheme. However, chirp-induced optical spectrum broadening is inevitable in complex modulated systems, which may imply a need for high-bandwidth receivers. In this Letter, we study the impact of receiver bandwidth effects on the performance of complex modulation and coherent detection systems based on DMLs. We experimentally demonstrate that such systems exhibit a reasonable tolerance for the reduced receiver bandwidth. For 10 Gbaud 4-level pulse amplitude modulation signals, the required electrical bandwidth is as low as 8.5 and 7.5 GHz for 7% and 20% forward error correction, respectively. Therefore, it is feasible to realize DML-based complex modulated systems using cost-effective receivers with narrow bandwidth.

Zinc as Allosteric Ion Channel Modulator: Ionotropic Receptors as Metalloproteins.

PubMed

Peralta, Francisco Andrés; Huidobro-Toro, Juan Pablo

2016-07-02

Zinc is an essential metal to life. This transition metal is a structural component of many proteins and is actively involved in the catalytic activity of cell enzymes. In either case, these zinc-containing proteins are metalloproteins. However, the amino acid residues that serve as ligands for metal coordination are not necessarily the same in structural proteins compared to enzymes. While crystals of structural proteins that bind zinc reveal a higher preference for cysteine sulfhydryls rather than histidine imidazole rings, catalytic enzymes reveal the opposite, i.e., a greater preference for the histidines over cysteines for catalysis, plus the influence of carboxylic acids. Based on this paradigm, we reviewed the putative ligands of zinc in ionotropic receptors, where zinc has been described as an allosteric modulator of channel receptors. Although these receptors do not strictly qualify as metalloproteins since they do not normally bind zinc in structural domains, they do transitorily bind zinc at allosteric sites, modifying transiently the receptor channel's ion permeability. The present contribution summarizes current information showing that zinc allosteric modulation of receptor channels occurs by the preferential metal coordination to imidazole rings as well as to the sulfhydryl groups of cysteine in addition to the carboxyl group of acid residues, as with enzymes and catalysis. It is remarkable that most channels, either voltage-sensitive or transmitter-gated receptor channels, are susceptible to zinc modulation either as positive or negative regulators.

Zinc as Allosteric Ion Channel Modulator: Ionotropic Receptors as Metalloproteins

PubMed Central

Peralta, Francisco Andrés; Huidobro-Toro, Juan Pablo

2016-01-01

Zinc is an essential metal to life. This transition metal is a structural component of many proteins and is actively involved in the catalytic activity of cell enzymes. In either case, these zinc-containing proteins are metalloproteins. However, the amino acid residues that serve as ligands for metal coordination are not necessarily the same in structural proteins compared to enzymes. While crystals of structural proteins that bind zinc reveal a higher preference for cysteine sulfhydryls rather than histidine imidazole rings, catalytic enzymes reveal the opposite, i.e., a greater preference for the histidines over cysteines for catalysis, plus the influence of carboxylic acids. Based on this paradigm, we reviewed the putative ligands of zinc in ionotropic receptors, where zinc has been described as an allosteric modulator of channel receptors. Although these receptors do not strictly qualify as metalloproteins since they do not normally bind zinc in structural domains, they do transitorily bind zinc at allosteric sites, modifying transiently the receptor channel’s ion permeability. The present contribution summarizes current information showing that zinc allosteric modulation of receptor channels occurs by the preferential metal coordination to imidazole rings as well as to the sulfhydryl groups of cysteine in addition to the carboxyl group of acid residues, as with enzymes and catalysis. It is remarkable that most channels, either voltage-sensitive or transmitter-gated receptor channels, are susceptible to zinc modulation either as positive or negative regulators. PMID:27384555

30 CFR 822.11 - Essential hydrologic functions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Essential hydrologic functions. 822.11 Section... IN ALLUVIAL VALLEY FLOORS § 822.11 Essential hydrologic functions. (a) The operator of a surface coal... throughout the mining and reclamation process the essential hydrologic functions of an alluvial valley floor...

Causal essentialism in kinds.

PubMed

Ahn, Woo-kyoung; Taylor, Eric G; Kato, Daniel; Marsh, Jessecae K; Bloom, Paul

2013-06-01

The current study examines causal essentialism, derived from psychological essentialism of concepts. We examine whether people believe that members of a category share some underlying essence that is both necessary and sufficient for category membership and that also causes surface features. The main claim is that causal essentialism is restricted to categories that correspond to our intuitive notions of existing kinds and hence is more attenuated for categories that are based on arbitrary criteria. Experiments 1 and 3 found that people overtly endorse causal essences in nonarbitrary kinds but are less likely to do so for arbitrary categories. Experiments 2 and 4 found that people were more willing to generalize a member's known causal relations (or lack thereof) when dealing with a kind than when dealing with an arbitrary category. These differences between kinds and arbitrary categories were found across various domains-not only for categories of living things, but also for artefacts. These findings have certain real-world implications, including how people make sense of mental disorders that are treated as real kinds.

Discussing Death, Dying, and End-of-Life Goals of Care: A Communication Skills Training Module for Oncology Nurses.

PubMed

Coyle, Nessa; Manna, Ruth; Shen, Megan; Banerjee, Smita C; Penn, Stacey; Pehrson, Cassandra; Krueger, Carol A; Maloney, Erin K; Zaider, Talia; Bylund, Carma L

2015-12-01

Effective communication, particularly at the end of life, is an essential skill for oncology nurses, but few receive formal training in this area. The aim of this article is to adapt an end-of-life care communication skills training (CST) module, originally developed for oncologists, for oncology nurses and to evaluate participants' confidence in using the communication skills learned and their satisfaction with the module. The adapted end-of-life care module consisted of a 45-minute didactic, exemplary video and 90 minutes of small group interaction and experiential role play with a simulated patient. Using a five-point Likert-type scale, 247 inpatient oncology nurses completed pre-/post-workshop surveys rating their confidence in discussing death, dying, and end-of-life goals of care with patients, as well as overall satisfaction with the module. Nurses' confidence in discussing death, dying, and end-of-life goals of care increased significantly after attending the workshop. Nurse participants indicated satisfaction with the module by agreeing or strongly agreeing to all six items assessing satisfaction 90%-98% of the time. Nurses' CST in discussing death, dying, and end-of-life care showed feasibility, acceptability, and potential benefit at improving confidence in having end-of-life care discussions.

Optical modulator system

NASA Technical Reports Server (NTRS)

Brand, J.

1972-01-01

The fabrication, test, and delivery of an optical modulator system which will operate with a mode-locked Nd:YAG laser indicating at either 1.06 or 0.53 micrometers is discussed. The delivered hardware operates at data rates up to 400 Mbps and includes a 0.53 micrometer electrooptic modulator, a 1.06 micrometer electrooptic modulator with power supply and signal processing electronics with power supply. The modulators contain solid state drivers which accept digital signals with MECL logic levels, temperature controllers to maintain a stable thermal environment for the modulator crystals, and automatic electronic compensation to maximize the extinction ratio. The modulators use two lithium tantalate crystals cascaded in a double pass configuration. The signal processing electronics include encoding electronics which are capable of digitizing analog signals between the limit of + or - 0.75 volts at a maximum rate of 80 megasamples per second with 5 bit resolution. The digital samples are serialized and made available as a 400 Mbps serial NRZ data source for the modulators. A pseudorandom (PN) generator is also included in the signal processing electronics. This data source generates PN sequences with lengths between 31 bits and 32,767 bits in a serial NRZ format at rates up to 400 Mbps.

Modulation Index Adjustment for Recovery of Pure Wavelength Modulation Spectroscopy Second Harmonic Signal Waveforms.

PubMed

Wei, Wei; Chang, Jun; Wang, Qiang; Qin, Zengguang

2017-01-15

A new technique of modulation index adjustment for pure wavelength modulation spectroscopy second harmonic signal waveforms recovery is presented. As the modulation index is a key parameter in determining the exact form of the signals generated by the technique of wavelength modulation spectroscopy, the method of modulation index adjustment is applied to recover the second harmonic signal with wavelength modulation spectroscopy. By comparing the measured profile with the theoretical profile by calculation, the relationship between the modulation index and average quantities of the scanning wavelength can be obtained. Furthermore, when the relationship is applied in the experimental setup by point-by-point modulation index modification for gas detection, the results show good agreement with the theoretical profile and signal waveform distortion (such as the amplitude modulation effect caused by diode laser) can be suppressed. Besides, the method of modulation index adjustment can be used in many other aspects which involve profile improvement. In practical applications, when the amplitude modulation effect can be neglected and the stability of the detection system is limited by the sampling rate of analog-to-digital, modulation index adjustment can be used to improve detection into softer inflection points and solve the insufficient sampling problem. As a result, measurement stability is improved by 40%.

Modulation Index Adjustment for Recovery of Pure Wavelength Modulation Spectroscopy Second Harmonic Signal Waveforms

PubMed Central

Wei, Wei; Chang, Jun; Wang, Qiang; Qin, Zengguang

2017-01-01

A new technique of modulation index adjustment for pure wavelength modulation spectroscopy second harmonic signal waveforms recovery is presented. As the modulation index is a key parameter in determining the exact form of the signals generated by the technique of wavelength modulation spectroscopy, the method of modulation index adjustment is applied to recover the second harmonic signal with wavelength modulation spectroscopy. By comparing the measured profile with the theoretical profile by calculation, the relationship between the modulation index and average quantities of the scanning wavelength can be obtained. Furthermore, when the relationship is applied in the experimental setup by point-by-point modulation index modification for gas detection, the results show good agreement with the theoretical profile and signal waveform distortion (such as the amplitude modulation effect caused by diode laser) can be suppressed. Besides, the method of modulation index adjustment can be used in many other aspects which involve profile improvement. In practical applications, when the amplitude modulation effect can be neglected and the stability of the detection system is limited by the sampling rate of analog-to-digital, modulation index adjustment can be used to improve detection into softer inflection points and solve the insufficient sampling problem. As a result, measurement stability is improved by 40%. PMID:28098842

Diffusion spectral imaging modules correlate with EEG LORETA neuroimaging modules.

PubMed

Thatcher, Robert W; North, Duane M; Biver, Carl J

2012-05-01

The purpose of this study was to test the hypothesis that the highest temporal correlations between 3-dimensional EEG current source density corresponds to anatomical Modules of high synaptic connectivity. Eyes closed and eyes open EEG was recorded from 19 scalp locations with a linked ears reference from 71 subjects age 13-42 years. LORETA was computed from 1 to 30 Hz in 2,394 cortical gray matter voxels that were grouped into six anatomical Modules corresponding to the ROIs in the Hagmann et al.'s [2008] diffusion spectral imaging (DSI) study. All possible cross-correlations between voxels within a DSI Module were compared with the correlations between Modules. The Hagmann et al. [ 2008] Module correlation structure was replicated in the correlation structure of EEG three-dimensional current source density. EEG Temporal correlation between brain regions is related to synaptic density as measured by diffusion spectral imaging. Copyright © 2011 Wiley-Liss, Inc.

Role of T Cell TGF-β Signaling in Intestinal Cytokine Responses and Helminthic Immune Modulation

PubMed Central

Ince, M. Nedim; Elliott, David E.; Setiawan, Tommy; Metwali, Ahmed; Blum, Arthur; Chen, Hung-lin; Urban, Joseph F.; Flavell, Richard A.; Weinstock, Joel V.

2010-01-01

Colonization with helminthic parasites induces mucosal regulatory cytokines, like IL-10 or TGF-β that are important in suppressing colitis. Helminths induce mucosal T cell IL-10 secretion and regulate lamina propria mononuclear cell Th1 cytokine generation in an IL-10 dependent manner in wild-type mice. Helminths also stimulate mucosal TGF-β release. As TGF-β exerts major regulatory effects on T lymphocytes, we investigated the role of T lymphocyte TGF-β signaling in helminthic modulation of intestinal immunity. T cell TGF-β signaling is interrupted in TGF-βRII DN mice by T cell-specific over-expression of a dominant negative TGF-β receptor II. We studied lamina propria mononuclear cell responses in wild-type and TGF-βRII DN mice that were uninfected or colonized with the nematode, Heligmosomoides polygyrus. Our results indicate an essential role of T cell TGF-β signaling in limiting mucosal Th1 and Th2 responses. Furthermore, we demonstrate that helminthic induction of intestinal T cell IL-10 secretion requires intact T cell TGF-β signaling pathway. Helminths fail to curtail robust, dysregulated intestinal Th1 cytokine production and chronic colitis in TGF-βRII DN mice. Thus, T cell TGF-β signaling is essential for helminthic stimulation of mucosal IL-10 production, helminthic modulation of intestinal interferon-γ generation and H. polygyrus-mediated suppression of chronic colitis. PMID:19544487

Delft3D turbine turbulence module v. 1.0.0

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

Chartrand, Chris; Jagers, Bert

2016-08-25

currents and waves act as driving forces and a wide variety of transport formulae have been incorporated. For the suspended load this module connects to the 2D or 3D advection-diffusion solver of the FLOW module; density effects may be taken into account. An essential feature of the MOR module is the dynamic feedback with the FLOW and WAVE modules, which allow the flows and waves to adjust themselves to the local bathymetry and allows for simulations on any time scale from days (storm impact) to centuries (system dynamics). It can keep track of the bed composition to build up a stratigraphic record. The MOR module may be extended to include extensive features to simulate dredging and dumping scenarios. For over 30 years Deltares has been in the forefront of these types of combined morphological simulation techniques.”« less

A design of optical modulation system with pixel-level modulation accuracy

NASA Astrophysics Data System (ADS)

Zheng, Shiwei; Qu, Xinghua; Feng, Wei; Liang, Baoqiu

2018-01-01

Vision measurement has been widely used in the field of dimensional measurement and surface metrology. However, traditional methods of vision measurement have many limits such as low dynamic range and poor reconfigurability. The optical modulation system before image formation has the advantage of high dynamic range, high accuracy and more flexibility, and the modulation accuracy is the key parameter which determines the accuracy and effectiveness of optical modulation system. In this paper, an optical modulation system with pixel level accuracy is designed and built based on multi-points reflective imaging theory and digital micromirror device (DMD). The system consisted of digital micromirror device, CCD camera and lens. Firstly we achieved accurate pixel-to-pixel correspondence between the DMD mirrors and the CCD pixels by moire fringe and an image processing of sampling and interpolation. Then we built three coordinate systems and calculated the mathematic relationship between the coordinate of digital micro-mirror and CCD pixels using a checkerboard pattern. A verification experiment proves that the correspondence error is less than 0.5 pixel. The results show that the modulation accuracy of system meets the requirements of modulation. Furthermore, the high reflecting edge of a metal circular piece can be detected using the system, which proves the effectiveness of the optical modulation system.

Programmable Thermostat Module Upgrade for the Multipurpose Logistics Module

NASA Technical Reports Server (NTRS)

Clark, D. W.; Glasgow, S. d.; Reagan, S. E.; Presson, K. H.; Howard, D. E.; Smith, D. A.

2007-01-01

The STS-121/ULF 1.1 mission was the maiden flight of the programmable thermostat module (PTM) system used to control the 28 V shell heaters on the multi-purpose logistics module (MPLM). These PTMs, in conjunction with a data recorder module (DRM), provide continuous closed loop temperature control and data recording of MPLM on-orbit heater operations. This Technical Memorandum discusses the hardware design, development, test, and verification (DDT&V) activities performed at the Marshall Space Flight Center as well as the operational implementation and mission performance.

Implementation of Black Sea numerical model based on NEMO and 3DVAR data assimilation scheme for operational forecasting

NASA Astrophysics Data System (ADS)

Ciliberti, Stefania Angela; Peneva, Elisaveta; Storto, Andrea; Rostislav, Kandilarov; Lecci, Rita; Yang, Chunxue; Coppini, Giovanni; Masina, Simona; Pinardi, Nadia

2016-04-01

This study describes a new model implementation for the Black Sea, which uses data assimilation, towards operational forecasting, based on NEMO (Nucleus for European Modelling of the Ocean, Madec et al., 2012). The Black Sea domain is resolved with 1/27°×1/36° horizontal resolution (~3 km) and 31 z-levels with partial steps based on the GEBCO bathymetry data (Grayek et al., 2010). The model is forced by momentum, water and heat fluxes interactively computed by bulk formulae using high resolution atmospheric forcing provided by the European Centre for Medium-Range Forecast (ECMWF). The initial condition is calculated from long-term climatological temperature and salinity 3D fields. Precipitation field over the basin has been computed from the climatological GPCP rainfall monthly data (Adler et al., 2003; Huffman et al., 2009), while the evaporation is derived from the latent heat flux. The climatological monthly mean runoff of the major rivers in the Black Sea is computed using the hydrological dataset provided by SESAME project (Ludvig et al., 2009). The exchange with Mediterranean Sea through the Bosporus Straits is represented by a surface boundary condition taking into account the barotropic transport calculated to balance the fresh water fluxes on monthly bases (Stanev and Beckers, 1999, Peneva et al., 2001). A multi-annual run 2011-2015 has been completed in order to describe the main characteristics of the Black Sea circulation dynamics and thermohaline structure and the numerical results have been validated using in-situ (ARGO) and satellite (SST, SLA) data. The Black Sea model represents also the core of the new Black Sea Forecasting System, implemented at CMCC operationally since January 2016, which produces at daily frequency 10-day forecasts, 3-days analyses and 1-day simulation. Once a week, the system is run 15-day in the past in analysis mode to compute the new optimal initial condition for the forecast cycle. The assimilation is performed by a

Stability of spanwise-modulated flows behind backward-facing steps

NASA Astrophysics Data System (ADS)

Boiko, A. V.; Dovgal, A. V.; Sorokin, A. M.

2017-10-01

An overview and synthesis of researches on development of local vortical disturbances in laminar separated flows downstream of backward-facing steps, in which the velocity field depends essentially on two variables are given. Peculiarities of transition to turbulence in such spatially inhomogeneous separated zones are discussed. The experimental data are supplemented by the linear stability characteristics of model velocity profiles of the separated flow computed using both the classical local formulation and the nonlocal approach based on the Floquet theory for partial differential equations with periodic coefficients. The results clarify the response of the local separated flows to their modulation with stationary geometrical and temperature inhomogeneities. The results can be useful for the development of new methods of laminar separation control.

Essential Oils, Part IV: Contact Allergy.

PubMed

de Groot, Anton C; Schmidt, Erich

2016-01-01

Nearly 80 essential oils (including 2 jasmine absolutes) have caused contact allergy. Fifty-five of these have been tested in consecutive patients suspected of contact dermatitis, and nine (laurel, turpentine, orange, tea tree, citronella, ylang-ylang, sandalwood, clove, and costus root) showed greater than 2% positive patch test reactions. Relevance data are generally missing or inadequate. Most reactions are caused by application of pure oils or high-concentration products. The clinical picture depends on the responsible product. Occupational contact dermatitis may occur in professionals performing massages. The (possible) allergens in essential oils are discussed. Several test allergens are available, but patients should preferably be tested with their own products. Co-reactivity with other essential oils and the fragrance mix is frequent, which may partly be explained by common ingredients. Patch test concentrations for essential oils are suggested.

Properties of genes essential for mouse development

PubMed Central

Kabir, Mitra; Barradas, Ana; Tzotzos, George T.; Hentges, Kathryn E.

2017-01-01

Essential genes are those that are critical for life. In the specific case of the mouse, they are the set of genes whose deletion means that a mouse is unable to survive after birth. As such, they are the key minimal set of genes needed for all the steps of development to produce an organism capable of life ex utero. We explored a wide range of sequence and functional features to characterise essential (lethal) and non-essential (viable) genes in mice. Experimental data curated manually identified 1301 essential genes and 3451 viable genes. Very many sequence features show highly significant differences between essential and viable mouse genes. Essential genes generally encode complex proteins, with multiple domains and many introns. These genes tend to be: long, highly expressed, old and evolutionarily conserved. These genes tend to encode ligases, transferases, phosphorylated proteins, intracellular proteins, nuclear proteins, and hubs in protein-protein interaction networks. They are involved with regulating protein-protein interactions, gene expression and metabolic processes, cell morphogenesis, cell division, cell proliferation, DNA replication, cell differentiation, DNA repair and transcription, cell differentiation and embryonic development. Viable genes tend to encode: membrane proteins or secreted proteins, and are associated with functions such as cellular communication, apoptosis, behaviour and immune response, as well as housekeeping and tissue specific functions. Viable genes are linked to transport, ion channels, signal transduction, calcium binding and lipid binding, consistent with their location in membranes and involvement with cell-cell communication. From the analysis of the composite features of essential and viable genes, we conclude that essential genes tend to be required for intracellular functions, and viable genes tend to be involved with extracellular functions and cell-cell communication. Knowledge of the features that are over

Perceptually Salient Regions of the Modulation Power Spectrum for Musical Instrument Identification.

PubMed

Thoret, Etienne; Depalle, Philippe; McAdams, Stephen

2017-01-01

The ability of a listener to recognize sound sources, and in particular musical instruments from the sounds they produce, raises the question of determining the acoustical information used to achieve such a task. It is now well known that the shapes of the temporal and spectral envelopes are crucial to the recognition of a musical instrument. More recently, Modulation Power Spectra (MPS) have been shown to be a representation that potentially explains the perception of musical instrument sounds. Nevertheless, the question of which specific regions of this representation characterize a musical instrument is still open. An identification task was applied to two subsets of musical instruments: tuba, trombone, cello, saxophone, and clarinet on the one hand, and marimba, vibraphone, guitar, harp, and viola pizzicato on the other. The sounds were processed with filtered spectrotemporal modulations with 2D Gaussian windows. The most relevant regions of this representation for instrument identification were determined for each instrument and reveal the regions essential for their identification. The method used here is based on a "molecular approach," the so-called bubbles method. Globally, the instruments were correctly identified and the lower values of spectrotemporal modulations are the most important regions of the MPS for recognizing instruments. Interestingly, instruments that were confused with each other led to non-overlapping regions and were confused when they were filtered in the most salient region of the other instrument. These results suggest that musical instrument timbres are characterized by specific spectrotemporal modulations, information which could contribute to music information retrieval tasks such as automatic source recognition.

Laying the foundation to use Raspberry Pi 3 V2 camera module imagery for scientific and engineering purposes

NASA Astrophysics Data System (ADS)

Pagnutti, Mary; Ryan, Robert E.; Cazenavette, George; Gold, Maxwell; Harlan, Ryan; Leggett, Edward; Pagnutti, James

2017-01-01

A comprehensive radiometric characterization of raw-data format imagery acquired with the Raspberry Pi 3 and V2.1 camera module is presented. The Raspberry Pi is a high-performance single-board computer designed to educate and solve real-world problems. This small computer supports a camera module that uses a Sony IMX219 8 megapixel CMOS sensor. This paper shows that scientific and engineering-grade imagery can be produced with the Raspberry Pi 3 and its V2.1 camera module. Raw imagery is shown to be linear with exposure and gain (ISO), which is essential for scientific and engineering applications. Dark frame, noise, and exposure stability assessments along with flat fielding results, spectral response measurements, and absolute radiometric calibration results are described. This low-cost imaging sensor, when calibrated to produce scientific quality data, can be used in computer vision, biophotonics, remote sensing, astronomy, high dynamic range imaging, and security applications, to name a few.

Bubble memory module

NASA Technical Reports Server (NTRS)

Bohning, O. D.; Becker, F. J.

1980-01-01

Design, fabrication and test of partially populated prototype recorder using 100 kilobit serial chips is described. Electrical interface, operating modes, and mechanical design of several module configurations are discussed. Fabrication and test of the module demonstrated the practicality of multiplexing resulting in lower power, weight, and volume. This effort resulted in the completion of a module consisting of a fully engineered printed circuit storage board populated with 5 of 8 possible cells and a wire wrapped electronics board. Interface of the module is 16 bits parallel at a maximum of 1.33 megabits per second data rate on either of two interface buses.

Solar energy modulator

NASA Technical Reports Server (NTRS)

Hale, R. R. (Inventor); Mcdougal, A. R.

1984-01-01

A module is described with a receiver having a solar energy acceptance opening and supported by a mounting ring along the optic axis of a parabolic mirror in coaxial alignment for receiving solar energy from the mirror, and a solar flux modulator plate for varying the quantity of solar energy flux received by the acceptance opening of the module. The modulator plate is characterized by an annular, plate-like body, the internal diameter of which is equal to or slightly greater than the diameter of the solar energy acceptance opening of the receiver. Slave cylinders are connected to the modulator plate for supporting the plate for axial displacement along the axis of the mirror, therby shading the opening with respect to solar energy flux reflected from the surface of the mirror to the solar energy acceptance opening.

Resource recovery from urban stock, the example of cadmium and tellurium from thin film module recycling

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

Simon, F.-G., E-mail: franz-georg.simon@bam.de; Holm, O.; Berger, W.

2013-04-15

Highlights: ► The semiconductor layer on thin-film photovoltaic modules can be removed from the glass-plate by vacuum blast cleaning. ► The separation of blasting agent and semiconductor can be performed using flotation with a valuable yield of 55%. ► PV modules are a promising source for the recovery of tellurium in the future. - Abstract: Raw material supply is essential for all industrial activities. The use of secondary raw material gains more importance since ore grade in primary production is decreasing. Meanwhile urban stock contains considerable amounts of various elements. Photovoltaic (PV) generating systems are part of the urban stockmore » and recycling technologies for PV thin film modules with CdTe as semiconductor are needed because cadmium could cause hazardous environmental impact and tellurium is a scarce element where future supply might be constrained. The paper describes a sequence of mechanical processing techniques for end-of-life PV thin film modules consisting of sandblasting and flotation. Separation of the semiconductor material from the glass surface was possible, however, enrichment and yield of valuables in the flotation step were non-satisfying. Nevertheless, recovery of valuable metals from urban stock is a viable method for the extension of the availability of limited natural resources.« less

Delta modulation

NASA Technical Reports Server (NTRS)

Schilling, D. L.

1971-01-01

The conclusions of the design research of the song adaptive delta modulator are presented for source encoding voice signals. The variation of output SNR vs input signal power/when 8, 9, and 10 bit internal arithmetic is employed. Voice intelligibility tapes to test the 10-bit system are used. An analysis of a delta modulator is also presented designed to minimize the in-band rms error. This is accomplished by frequency shaping the error signal in the modulator prior to hard limiting. The result is a significant increase in the output SNR measured after low pass filtering.

Fluence-field modulated x-ray CT using multiple aperture devices

NASA Astrophysics Data System (ADS)

Stayman, J. Webster; Mathews, Aswin; Zbijewski, Wojciech; Gang, Grace; Siewerdsen, Jeffrey; Kawamoto, Satomi; Blevis, Ira; Levinson, Reuven

2016-03-01

We introduce a novel strategy for fluence field modulation (FFM) in x-ray CT using multiple aperture devices (MADs). MAD filters permit FFM by blocking or transmitting the x-ray beam on a fine (0.1-1 mm) scale. The filters have a number of potential advantages over other beam modulation strategies including the potential for a highly compact design, modest actuation speed and acceleration requirements, and spectrally neutral filtration due to their essentially binary action. In this work, we present the underlying MAD filtration concept including a design process to achieve a specific class of FFM patterns. A set of MAD filters is fabricated using a tungsten laser sintering process and integrated into an x-ray CT test bench. A characterization of the MAD filters is conducted and compared to traditional attenuating bowtie filters and the ability to flatten the fluence profile for a 32 cm acrylic phantom is demonstrated. MAD-filtered tomographic data was acquired on the CT test bench and reconstructed without artifacts associated with the MAD filter. These initial studies suggest that MAD-based FFM is appropriate for integration in clinical CT system to create patient-specific fluence field profile and reduce radiation exposures.

Japanese Experiment Module arrival

NASA Image and Video Library

2007-03-29

Several components for delivery to the International Space Station sit in test stands inside the Space Station Processing Facility highbay. To the right, from back to front, are the Japanese Experiment Module, the Raffaello multi-purpose logistics module, and the European Space Agency's Columbus scientific research module. To the left in front is the starboard truss segment S5. Behind it is the test stand that will hold the Experiment Logistics Module Pressurized Section for the Japanese Experiment Module. The logistics module is one of the components of the Japanese Experiment Module or JEM, also known as Kibo, which means "hope" in Japanese. Kibo comprises six components: two research facilities -- the Pressurized Module and Exposed Facility; a Logistics Module attached to each of them; a Remote Manipulator System; and an Inter-Orbit Communication System unit. Kibo also has a scientific airlock through which experiments are transferred and exposed to the external environment of space. Kibo is Japan's first human space facility and its primary contribution to the station. Kibo will enhance the unique research capabilities of the orbiting complex by providing an additional environment in which astronauts can conduct science experiments. The various components of JEM will be assembled in space over the course of three Space Shuttle missions. The first of those three missions, STS-123, will carry the Experiment Logistics Module Pressurized Section aboard the Space Shuttle Endeavour, targeted for launch in 2007.

Lunar Module 4 moved for mating with Lunar Module Adapter at KSC

NASA Technical Reports Server (NTRS)

1969-01-01

Lunar Module 4 being moved for mating with the Spacecraft Lunar Module Adapter in the Kennedy Space Center's (KSC) Manned Spacecraft Operations Building. Lunar module 4 will be flown on the Apollo 10 (Spacecraft 106/Saturn 505) lunar orbit mission.

Antifungal Activity of Essential Oils against Candida albicans Strains Isolated from Users of Dental Prostheses

PubMed Central

Júnior, José Klidenberg de Oliveira; Silva, Daniele de Figueredo; de Sousa, Janiere Pereira; Guerra, Felipe Queiroga Sarmento; de Oliveira Lima, Edeltrudes

2017-01-01

Objective The objective of this study was to analyze the antifungal activity of citral, selected by screening natural products, against Candida albicans isolates from subjects who use dental prostheses. Methodology Screening of essential oils, including those from Mentha piperita L. (Briq), Origanum vulgare, and Zingiber officinale L., and the phytoconstituents citral and limonene, to select an appropriate natural product. Citral, which mediated the best antifungal response, was selected for biological assays. The minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) for citral and nystatin were determined by the microdilution method. Micromorphological analyses, time-kill curve, and modulation tests were performed. Results The MIC and MFC of citral were established as 32 μg/mL, consistent with fungicidal activity. The clinical strains were resistant to nystatin. Citral caused micromorphological alteration in the strains. In the time-kill curve, the growth of the clinical strain was reduction in growth equal to 3 log10 colony-forming units per milliliter after exposure to the MIC and MIC × 2 of citral for 2 h. Citral did not modulate the resistance of the studied strains to nystatin. Conclusion This study revealed the potential of citral as a fungicidal agent and highlighted the resistance of clinical strains of C. albicans to nystatin. PMID:29234423

Modeling stochastic kinetics of molecular machines at multiple levels: from molecules to modules.

PubMed

Chowdhury, Debashish

2013-06-04

A molecular machine is either a single macromolecule or a macromolecular complex. In spite of the striking superficial similarities between these natural nanomachines and their man-made macroscopic counterparts, there are crucial differences. Molecular machines in a living cell operate stochastically in an isothermal environment far from thermodynamic equilibrium. In this mini-review we present a catalog of the molecular machines and an inventory of the essential toolbox for theoretically modeling these machines. The tool kits include 1), nonequilibrium statistical-physics techniques for modeling machines and machine-driven processes; and 2), statistical-inference methods for reverse engineering a functional machine from the empirical data. The cell is often likened to a microfactory in which the machineries are organized in modular fashion; each module consists of strongly coupled multiple machines, but different modules interact weakly with each other. This microfactory has its own automated supply chain and delivery system. Buoyed by the success achieved in modeling individual molecular machines, we advocate integration of these models in the near future to develop models of functional modules. A system-level description of the cell from the perspective of molecular machinery (the mechanome) is likely to emerge from further integrations that we envisage here. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Modeling Stochastic Kinetics of Molecular Machines at Multiple Levels: From Molecules to Modules

PubMed Central

Chowdhury, Debashish

2013-01-01

A molecular machine is either a single macromolecule or a macromolecular complex. In spite of the striking superficial similarities between these natural nanomachines and their man-made macroscopic counterparts, there are crucial differences. Molecular machines in a living cell operate stochastically in an isothermal environment far from thermodynamic equilibrium. In this mini-review we present a catalog of the molecular machines and an inventory of the essential toolbox for theoretically modeling these machines. The tool kits include 1), nonequilibrium statistical-physics techniques for modeling machines and machine-driven processes; and 2), statistical-inference methods for reverse engineering a functional machine from the empirical data. The cell is often likened to a microfactory in which the machineries are organized in modular fashion; each module consists of strongly coupled multiple machines, but different modules interact weakly with each other. This microfactory has its own automated supply chain and delivery system. Buoyed by the success achieved in modeling individual molecular machines, we advocate integration of these models in the near future to develop models of functional modules. A system-level description of the cell from the perspective of molecular machinery (the mechanome) is likely to emerge from further integrations that we envisage here. PMID:23746505

Electro-Optic Modulator and Method

DTIC Science & Technology

An optical intensity modulator which uses a Sagnac interferometer having an electro - optic phase modulator therein. An electric modulation signal is...modulating the optical signals by the electrical signal, the electro - optic effect in the modulator phase shifts the optical signals with respect to one another

Integrated unaligned resonant modulator tuning

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

Zortman, William A.; Lentine, Anthony L.

Methods and systems for tuning a resonant modulator are disclosed. One method includes receiving a carrier signal modulated by the resonant modulator with a stream of data having an approximately equal number of high and low bits, determining an average power of the modulated carrier signal, comparing the average power to a predetermined threshold, and operating a tuning device coupled to the resonant modulator based on the comparison of the average power and the predetermined threshold. One system includes an input structure, a plurality of processing elements, and a digital control element. The input structure is configured to receive, frommore » the resonant modulator, a modulated carrier signal. The plurality of processing elements are configured to determine an average power of the modulated carrier signal. The digital control element is configured to operate a tuning device coupled to the resonant modulator based on the average power of the modulated carrier signal.« less

Apollo 17 Command/Service modules photographed from lunar module in orbit

NASA Image and Video Library

1972-12-14

AS17-145-22254 (14 Dec. 1972) --- An excellent view of the Apollo 17 Command and Service Modules (CSM) photographed from the Lunar Module (LM) "Challenger" during rendezvous and docking maneuvers in lunar orbit. The LM ascent stage, with astronauts Eugene A. Cernan and Harrison H. Schmitt aboard, had just returned from the Taurus-Littrow landing site on the lunar surface. Astronaut Ronald E. Evans remained with the CSM in lunar orbit. Note the exposed Scientific Instrument Module (SIM) Bay in Sector 1 of the Service Module (SM). Three experiments are carried in the SIM bay: S-209 lunar sounder, S-171 infrared scanning spectrometer, and the S-169 far-ultraviolet spectrometer. Also mounted in the SIM bay are the panoramic camera, mapping camera and laser altimeter used in service module photographic tasks. A portion of the LM is on the right.

Network analysis of S. aureus response to ramoplanin reveals modules for virulence factors and resistance mechanisms and characteristic novel genes.

PubMed

Subramanian, Devika; Natarajan, Jeyakumar

2015-12-10

Staphylococcus aureus is a major human pathogen and ramoplanin is an antimicrobial attributed for effective treatment. The goal of this study was to examine the transcriptomic profiles of ramoplanin sensitive and resistant S. aureus to identify putative modules responsible for virulence and resistance-mechanisms and its characteristic novel genes. The dysregulated genes were used to reconstruct protein functional association networks for virulence-factors and resistance-mechanisms individually. Strong link between metabolic-pathways and development of virulence/resistance is suggested. We identified 15 putative modules of virulence factors. Six hypothetical genes were annotated with novel virulence activity among which SACOL0281 was discovered to be an essential virulence factor EsaD. The roles of MazEF toxin-antitoxin system, SACOL0202/SACOL0201 two-component system and that of amino-sugar and nucleotide-sugar metabolism in virulence are also suggested. In addition, 14 putative modules of resistance mechanisms including modules of ribosomal protein-coding genes and metabolic pathways such as biotin-synthesis, TCA-cycle, riboflavin-biosynthesis, peptidoglycan-biosynthesis etc. are also indicated. Copyright © 2015 Elsevier B.V. All rights reserved.

I Feel You: The Design and Evaluation of a Domotic Affect-Sensitive Spoken Conversational Agent

PubMed Central

Lutfi, Syaheerah Lebai; Fernández-Martínez, Fernando; Lorenzo-Trueba, Jaime; Barra-Chicote, Roberto; Montero, Juan Manuel

2013-01-01

We describe the work on infusion of emotion into a limited-task autonomous spoken conversational agent situated in the domestic environment, using a need-inspired task-independent emotion model (NEMO). In order to demonstrate the generation of affect through the use of the model, we describe the work of integrating it with a natural-language mixed-initiative HiFi-control spoken conversational agent (SCA). NEMO and the host system communicate externally, removing the need for the Dialog Manager to be modified, as is done in most existing dialog systems, in order to be adaptive. The first part of the paper concerns the integration between NEMO and the host agent. The second part summarizes the work on automatic affect prediction, namely, frustration and contentment, from dialog features, a non-conventional source, in the attempt of moving towards a more user-centric approach. The final part reports the evaluation results obtained from a user study, in which both versions of the agent (non-adaptive and emotionally-adaptive) were compared. The results provide substantial evidences with respect to the benefits of adding emotion in a spoken conversational agent, especially in mitigating users' frustrations and, ultimately, improving their satisfaction. PMID:23945740

The BiPo-3 detector for the measurement of ultra low natural radioactivities of thin materials

NASA Astrophysics Data System (ADS)

Barabash, A. S.; Basharina-Freshville, A.; Birdsall, E.; Blondel, S.; Blot, S.; Bongrand, M.; Boursette, D.; Brudanin, V.; Busto, J.; Caffrey, A. J.; Calvez, S.; Cascella, M.; Cebrián, S.; Cerna, C.; Cesar, J. P.; Chauveau, E.; Chopra, A.; Dafní, T.; De Capua, S.; Duchesneau, D.; Durand, D.; Egorov, V.; Eurin, G.; Evans, J. J.; Fajt, L.; Filosofov, D.; Flack, R.; Garrido, X.; Gómez, H.; Guillon, B.; Guzowski, P.; Holý, K.; Hodák, R.; Huber, A.; Hugon, C.; Iguaz, F. J.; Irastorza, I. G.; Jeremie, A.; Jullian, S.; Kauer, M.; Klimenko, A.; Kochetov, O.; Konovalov, S. I.; Kovalenko, V.; Lang, K.; Lemière, Y.; Le Noblet, T.; Liptak, Z.; Liu, X. R.; Loaiza, P.; Lutter, G.; Luzón, G.; Macko, M.; Mamedov, F.; Marquet, C.; Mauger, F.; Morgan, B.; Mott, J.; Nemchenok, I.; Nomachi, M.; Nova, F.; Ohsumi, H.; Oliviéro, G.; Ortiz de Solórzano, A.; Pahlka, R. B.; Pater, J.; Perrot, F.; Piquemal, F.; Povinec, P.; Přidal, P.; Ramachers, Y. A.; Remoto, A.; Richards, B.; Riddle, C. L.; Rukhadze, E.; Saakyan, R.; Salazar, R.; Sarazin, X.; Shitov, Yu.; Simard, L.; Šimkovic, F.; Smetana, A.; Smolek, K.; Smolnikov, A.; Söldner-Rembold, S.; Soulé, B.; Štekl, I.; Thomas, J.; Timkin, V.; Torre, S.; Tretyak, Vl. I.; Tretyak, V. I.; Umatov, V. I.; Vilela, C.; Vorobel, V.; Waters, D.; Žukauskas, A.

2017-06-01

The BiPo-3 detector, running at the Canfranc Underground Laboratory (Laboratorio Subterr&aposaneo de Canfranc, LSC, Spain) since 2013, is a low-radioactivity detector dedicated to measuring ultra low natural radionuclide contaminations of 208Tl (232Th chain) and 214Bi (238U chain) in thin materials. The total sensitive surface area of the detector is 3.6 m2. The detector has been developed to measure the radiopurity of the selenium double β-decay source foils of the SuperNEMO experiment. In this paper the design and performance of the detector, and results of the background measurements in 208Tl and 214Bi, are presented, and the validation of the BiPo-3 measurement with a calibrated aluminium foil is discussed. Results of the 208Tl and 214Bi activity measurements of the first enriched 82Se foils of the double β-decay SuperNEMO experiment are reported. The sensitivity of the BiPo-3 detector for the measurement of the SuperNEMO 82Se foils is Script A(208Tl) <2 μBq/kg (90% C.L.) and Script A(214Bi) <140 μBq/kg (90% C.L.) after 6 months of measurement.

Essential Oils: Sources of Antimicrobials and Food Preservatives

PubMed Central

Pandey, Abhay K.; Kumar, Pradeep; Singh, Pooja; Tripathi, Nijendra N.; Bajpai, Vivek K.

2017-01-01

Aromatic and medicinal plants produce essential oils in the form of secondary metabolites. These essential oils can be used in diverse applications in food, perfume, and cosmetic industries. The use of essential oils as antimicrobials and food preservative agents is of concern because of several reported side effects of synthetic oils. Essential oils have the potential to be used as a food preservative for cereals, grains, pulses, fruits, and vegetables. In this review, we briefly describe the results in relevant literature and summarize the uses of essential oils with special emphasis on their antibacterial, bactericidal, antifungal, fungicidal, and food preservative properties. Essential oils have pronounced antimicrobial and food preservative properties because they consist of a variety of active constituents (e.g., terpenes, terpenoids, carotenoids, coumarins, curcumins) that have great significance in the food industry. Thus, the various properties of essential oils offer the possibility of using natural, safe, eco-friendly, cost-effective, renewable, and easily biodegradable antimicrobials for food commodity preservation in the near future. PMID:28138324

Microbicide activity of clove essential oil (Eugenia caryophyllata)

PubMed Central

Nuñez, L.; Aquino, M. D’

2012-01-01

Clove essential oil, used as an antiseptic in oral infections, inhibits Gram-negative and Gram-positive bacteria as well as yeast. The influence of clove essential oil concentration, temperature and organic matter, in the antimicrobial activity of clove essential oil, was studied in this paper, through the determination of bacterial death kinetics. Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa were the microorganisms selected for a biological test. To determine the temperature effect, they were assayed at 21° and 37° C. The concentration coefficient was determined with 0.4%, and 0.2% of essential oil. The influence of the presence of organic matter was determined with 0.4% of essential oil. The results obtained demonstrated that Escherichia coli were more sensitive even though the essential oil exerted a satisfactory action in three cases. In the three microbial species, 0.4% of essential oil at 21° C have reduced the bacterial population in 5 logarithmic orders. Organic matter reduces the antibacterial activity even though the bactericide efficacy was not lost. Clove essential oil can be considered as a potential antimicrobial agent for external use PMID:24031950

Cultural transmission of social essentialism

PubMed Central

Rhodes, Marjorie; Leslie, Sarah-Jane; Tworek, Christina M.

2012-01-01

Social essentialism entails the belief that certain social categories (e.g., gender, race) mark fundamentally distinct kinds of people. Essentialist beliefs have pernicious consequences, supporting social stereotyping and contributing to prejudice. How does social essentialism develop? In the studies reported here, we tested the hypothesis that generic language facilitates the cultural transmission of social essentialism. Two studies found that hearing generic language about a novel social category diverse for race, ethnicity, age, and sex led 4-y-olds and adults to develop essentialist beliefs about that social category. A third study documented that experimentally inducing parents to hold essentialist beliefs about a novel social category led them to produce more generic language when discussing the category with their children. Thus, generic language facilitates the transmission of essentialist beliefs about social categories from parents to children. PMID:22869722

Management of Essential Hypertension.

PubMed

Ferdinand, Keith C; Nasser, Samar A

2017-05-01

The treatment of essential hypertension is one of the most critical interventions to decrease cardiovascular morbidity and mortality. The prevalence of hypertension in the US varies across race/ethnicity with African Americans having the highest prevalence and overall less control among racial/ethnic minorities compared with non-Hispanic whites. Therapeutic lifestyle modifications are the bedrock of essential hypertension control, but most patients with hypertension will require pharmacotherapy, usually with multiple medications often in combination. Overall, the principal drug classes recommended as initial pharmacotherapy are thiazide-type diuretics, calcium channel blockers, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Copyright © 2016 Elsevier Inc. All rights reserved.

Informatics Essentials for DNPs.

PubMed

Jenkins, Melinda L

2018-01-01

Doctor of Nursing Practice (DNP) programs are proliferating around the US as advanced practice nursing programs evolve to build capacity by adding content on professional leadership, policy, and quality improvement to the traditional clinical content. One of the eight "Essentials" for DNP education is "Information systems/technology and patient care technology for the improvement and transformation of health care."[1] A required graduate course was revised and updated in 2017 to provide a foundation in clinical informatics for DNPs, as well as for nursing informatics specialists. Components of the online course, assignments, and free online resources linked to the DNP Essentials are described in this paper.

Amplitude Modulator Chassis

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

Erbert, G

2009-09-01

The Amplitude Modulator Chassis (AMC) is the final component in the MOR system and connects directly to the PAM input through a 100-meter fiber. The 48 AMCs temporally shape the 48 outputs of the MOR using an arbitrary waveform generator coupled to an amplitude modulator. The amplitude modulation element is a two stage, Lithium Niobate waveguide device, where the intensity of the light passing through the device is a function of the electrical drive applied. The first stage of the modulator is connected to a programmable high performance Arbitrary Waveform Generator (AWG) consisting of 140 impulse generators space 250 psmore » apart. An arbitrary waveform is generated by independently varying the amplitude of each impulse generator and then summing the impulses together. In addition to the AWG a short pulse generator is also connected to the first stage of the modulator to provide a sub 100-ps pulse used for timing experiments. The second stage of the modulator is connect to a square pulse generator used to further attenuate any pre or post pulse light passing through the first stage of the modulator. The fast rise and fall time of the square pulse generator is also used to produce fast rise and fall times of the AWG by clipping the AWG pulse. For maximum extinction, a pulse bias voltage is applied to each stage of the modulator. A pulse voltage is applied as opposed to a DC voltage to prevent charge buildup on the modulator. Each bias voltage is adjustable to provide a minimum of 50-dB extinction. The AMC is controlled through ICCS to generate the desired temporal pulse shape. This process involves a closed-loop control algorithm, which compares the desired temporal waveform to the produced optical pulse, and iterates the programming of the AWG until the two waveforms agree within an allowable tolerance.« less

Orion Crew Module Adapter

NASA Image and Video Library

2015-11-12

Offloading of the Orion Crew Module Adapter, CMA, at Plum Brook Station. The adapter will connect Orion’s crew module to a service module provided by ESA (European Space Agency). NASA is preparing for a series of tests that will check out the Orion European Service Module, a critical part of the spacecraft that will be launched on future missions to an asteroid and on toward Mars.

Essentials of Career Interest Assessment. Essentials of Psychological Assessment Series.

ERIC Educational Resources Information Center

Prince, Jeffrey P.; Heiser, Lisa J.

This book is a quick reference source to guide the career professional through the essentials of using the most popular career interest tools. It summarizes important technical aspects of each inventory, and offers step-by-step guidance in the interpretation and use of the various inventories. The chapters are: (1) "Overview"; (2)…

Modulation of frontal effective connectivity during speech.

PubMed

Holland, Rachel; Leff, Alex P; Penny, William D; Rothwell, John C; Crinion, Jenny

2016-10-15

Noninvasive neurostimulation methods such as transcranial direct current stimulation (tDCS) can elicit long-lasting, polarity-dependent changes in neocortical excitability. In a previous concurrent tDCS-fMRI study of overt picture naming, we reported significant behavioural and regionally specific neural facilitation effects in left inferior frontal cortex (IFC) with anodal tDCS applied to left frontal cortex (Holland et al., 2011). Although distributed connectivity effects of anodal tDCS have been modelled at rest, the mechanism by which 'on-line' tDCS may modulate neuronal connectivity during a task-state remains unclear. Here, we used Dynamic Causal Modelling (DCM) to determine: (i) how neural connectivity within the frontal speech network is modulated during anodal tDCS; and, (ii) how individual variability in behavioural response to anodal tDCS relates to changes in effective connectivity strength. Results showed that compared to sham, anodal tDCS elicited stronger feedback from inferior frontal sulcus (IFS) to ventral premotor (VPM) accompanied by weaker self-connections within VPM, consistent with processes of neuronal adaptation. During anodal tDCS individual variability in the feedforward connection strength from IFS to VPM positively correlated with the degree of facilitation in naming behaviour. These results provide an essential step towards understanding the mechanism of 'online' tDCS paired with a cognitive task. They also identify left IFS as a 'top-down' hub and driver for speech change. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Essential Kinematics for Autonomous Vehicles

DTIC Science & Technology

1994-05-02

AD-.A282 456 Essential Kinematics for Autonomous Vehicles Alonzo Kelly DTICCMU-RI-TR-94- 14 AU 031994 F The Robotics Institute Carnegie Mellon...kit of concepts and techniques that will equip the reader to master a large class of kinematic modelling problems. Control of autonomous vehicles in 3D...transformation from system ’a’ to system b’. Essential Kinematics for Autonomous Vehicles page 1. The specification of derivatives will be necessarily

Micro-electro-mechanical systems (MEMS) and agile lensing-based modules for communications, sensing and signal processing

NASA Astrophysics Data System (ADS)

Reza, Syed Azer

This dissertation proposes the use of the emerging Micro-Electro-Mechanical Systems (MEMS) and agile lensing optical device technologies to design novel and powerful signal conditioning and sensing modules for advanced applications in optical communications, physical parameter sensing and RF/optical signal processing. For example, these new module designs have experimentally demonstrated exceptional features such as stable loss broadband operations and high > 60 dB optical dynamic range signal filtering capabilities. The first part of the dissertation describes the design and demonstration of digital MEMS-based signal processing modules for communication systems and sensor networks using the TI DLP (Digital Light Processing) technology. Examples of such modules include optical power splitters, narrowband and broadband variable fiber optical attenuators, spectral shapers and filters. Compared to prior works, these all-digital designs have advantages of repeatability, accuracy, and reliability that are essential for advanced communications and sensor applications. The next part of the dissertation proposes, analyzes and demonstrates the use of analog opto-fluidic agile lensing technology for sensor networks and test and measurement systems. Novel optical module designs for distance sensing, liquid level sensing, three-dimensional object shape sensing and variable photonic delay lines are presented and experimentally demonstrated. Compared to prior art module designs, the proposed analog-mode modules have exceptional performances, particularly for extreme environments (e.g., caustic liquids) where the free-space agile beam-based sensor provide remote non-contact access for physical sensing operations. The dissertation also presents novel modules involving hybrid analog-digital photonic designs that make use of the different optical device technologies to deliver the best features of both analog and digital optical device operations and controls. Digital controls are

Highly Sensitive Electro-Optic Modulators

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

DeVore, Peter S

2015-10-26

There are very important diagnostic and communication applications that receive faint electrical signals to be transmitted over long distances for capture. Optical links reduce bandwidth and distance restrictions of metal transmission lines; however, such signals are only weakly imprinted onto the optical carrier, resulting in low fidelity transmission. Increasing signal fidelity often necessitates insertion of radio-frequency (RF) amplifiers before the electro-optic modulator, but (especially at high frequencies) RF amplification results in large irreversible distortions. We have investigated the feasibility of a Sensitive and Linear Modulation by Optical Nonlinearity (SALMON) modulator to supersede RF-amplified modulators. SALMON uses cross-phase modulation, a manifestationmore » of the Kerr effect, to enhance the modulation depth of an RF-modulated optical wave. This ultrafast process has the potential to result in less irreversible distortions as compared to a RF-amplified modulator due to the broadband nature of the Kerr effect. Here, we prove that a SALMON modulator is a feasible alternative to an RFamplified modulator, by demonstrating a sensitivity enhancement factor greater than 20 and significantly reduced distortion.« less

Phase modulation in RF tag

DOEpatents

Carrender, Curtis Lee; Gilbert, Ronald W.

2007-02-20

A radio frequency (RF) communication system employs phase-modulated backscatter signals for RF communication from an RF tag to an interrogator. The interrogator transmits a continuous wave interrogation signal to the RF tag, which based on an information code stored in a memory, phase-modulates the interrogation signal to produce a backscatter response signal that is transmitted back to the interrogator. A phase modulator structure in the RF tag may include a switch coupled between an antenna and a quarter-wavelength stub; and a driver coupled between the memory and a control terminal of the switch. The driver is structured to produce a modulating signal corresponding to the information code, the modulating signal alternately opening and closing the switch to respectively decrease and increase the transmission path taken by the interrogation signal and thereby modulate the phase of the response signal. Alternatively, the phase modulator may include a diode coupled between the antenna and driver. The modulating signal from the driver modulates the capacitance of the diode, which modulates the phase of the response signal reflected by the diode and antenna.

BRDT is an essential epigenetic regulator for proper chromatin organization, silencing of sex chromosomes and crossover formation in male meiosis

PubMed Central

Oh, Min Young; Garyn, Corey

2018-01-01

The double bromodomain and extra-terminal domain (BET) proteins are critical epigenetic readers that bind to acetylated histones in chromatin and regulate transcriptional activity and modulate changes in chromatin structure and organization. The testis-specific BET member, BRDT, is essential for the normal progression of spermatogenesis as mutations in the Brdt gene result in complete male sterility. Although BRDT is expressed in both spermatocytes and spermatids, loss of the first bromodomain of BRDT leads to severe defects in spermiogenesis without overtly compromising meiosis. In contrast, complete loss of BRDT blocks the progression of spermatocytes into the first meiotic division, resulting in a complete absence of post-meiotic cells. Although BRDT has been implicated in chromatin remodeling and mRNA processing during spermiogenesis, little is known about its role in meiotic processes. Here we report that BRDT is an essential regulator of chromatin organization and reprograming during prophase I of meiosis. Loss of BRDT function disrupts the epigenetic state of the meiotic sex chromosome inactivation in spermatocytes, affecting the synapsis and silencing of the X and Y chromosomes. We also found that BRDT controls the global chromatin organization and histone modifications of the chromatin attached to the synaptonemal complex. Furthermore, the homeostasis of crossover formation and localization during pachynema was altered, underlining a possible epigenetic mechanism by which crossovers are regulated and differentially established in mammalian male genomes. Our observations reveal novel findings about the function of BRDT in meiosis and provide insight into how epigenetic regulators modulate the progression of male mammalian meiosis and the formation of haploid gametes. PMID:29513658

Four Essential Dimensions of Workplace Learning

ERIC Educational Resources Information Center

Hopwood, Nick

2014-01-01

Purpose: This conceptual paper aims to argue that times, spaces, bodies and things constitute four essential dimensions of workplace learning. It examines how practices relate or hang together, taking Gherardi's texture of practices or connectedness in action as the foundation for making visible essential but often overlooked dimensions of…

Inflammation in the pathophysiology of essential hypertension.

PubMed

Montecucco, Fabrizio; Pende, Aldo; Quercioli, Alessandra; Mach, François

2011-01-01

In spite of the huge amount of research recently performed in this area, the pathogenesis of human hypertension remains elusive. Thus, hypertension has to be defined as "essential" for the majority of patients with high blood pressure. Given the lack of animal models useful to investigate essential hypertension, we analyze and discuss both clinical and basic research studies indicating that essential hypertension should be considered as a potential multifactorial inflammatory disease. The pathophysiology of essential hypertension might result from interactions between genetic and environmental factors. Morphological abnormalities in the renal parenchyma and arteries have also been shown to determine hypertension. Inflammatory processes might induce renal vasoconstriction, ischemia and injury that can sustain systemic hypertension. Arterial and tubulointerstitial infiltration of inflammatory cells in response to renal damage might further increase renal and vascular alterations through the production of oxidants and other soluble inflammatory mediators. The present review gives an update regarding the latest research on the possible direct role of inflammation in the pathophysiology of essential hypertension.

Osmotic modulation of chromatin impacts on efficiency and kinetics of cell fate modulation.

PubMed

Lima, A F; May, G; Colunga, J; Pedreiro, S; Paiva, A; Ferreira, L; Enver, T; Iborra, F J; Pires das Neves, R

2018-05-08

Chromatin structure is a major regulator of transcription and gene expression. Herein we explore the use of osmotic modulation to modify the chromatin structure and reprogram gene expression. In this study we use the extracellular osmotic pressure as a chromatin structure and transcriptional modulator. Hyposmotic modulation promotes chromatin loosening and induces changes in RNA polymerase II (Pol II) activity. The chromatin decondensation opens space for higher amounts of DNA engaged RNA Pol II. Hyposmotic modulation constitutes an alternative route to manipulate cell fate decisions. This technology was tested in model protocols of induced pluripotency and transdifferentiation in cells growing in suspension and adherent to substrates, CD34 + umbilical-cord-blood (UCB), fibroblasts and B-cells. The efficiency and kinetics of these cell fate modulation processes were improved by transient hyposmotic modulation of the cell environment.

Japanese Experiment Module arrival

NASA Image and Video Library

2007-03-29

The Experiment Logistics Module Pressurized Section for the Japanese Experiment Module arrives at the Space Station Processing Facility. The logistics module is one of the components of the Japanese Experiment Module or JEM, also known as Kibo, which means "hope" in Japanese. Kibo comprises six components: two research facilities -- the Pressurized Module and Exposed Facility; a Logistics Module attached to each of them; a Remote Manipulator System; and an Inter-Orbit Communication System unit. Kibo also has a scientific airlock through which experiments are transferred and exposed to the external environment of space. Kibo is Japan's first human space facility and its primary contribution to the station. Kibo will enhance the unique research capabilities of the orbiting complex by providing an additional environment in which astronauts can conduct science experiments. The various components of JEM will be assembled in space over the course of three Space Shuttle missions. The first of those three missions, STS-123, will carry the Experiment Logistics Module Pressurized Section aboard the Space Shuttle Endeavour, targeted for launch in 2007.

Japanese Experiment Module arrival

NASA Image and Video Library

2007-03-29

Inside the Space Station Processing Facility, the Experiment Logistics Module Pressurized Section for the Japanese Experiment Module is revealed after the top of the crate is removed. The logistics module is one of the components of the Japanese Experiment Module or JEM, also known as Kibo, which means "hope" in Japanese. Kibo comprises six components: two research facilities -- the Pressurized Module and Exposed Facility; a Logistics Module attached to each of them; a Remote Manipulator System; and an Inter-Orbit Communication System unit. Kibo also has a scientific airlock through which experiments are transferred and exposed to the external environment of space. Kibo is Japan's first human space facility and its primary contribution to the station. Kibo will enhance the unique research capabilities of the orbiting complex by providing an additional environment in which astronauts can conduct science experiments. The various components of JEM will be assembled in space over the course of three Space Shuttle missions. The first of those three missions, STS-123, will carry the Experiment Logistics Module Pressurized Section aboard the Space Shuttle Endeavour, targeted for launch in 2007.

Japanese Experiment Module arrival

NASA Image and Video Library

2007-03-29

The Experiment Logistics Module Pressurized Section for the Japanese Experiment Module arrives at the Space Station Processing Facility for uncrating. The logistics module is one of the components of the Japanese Experiment Module or JEM, also known as Kibo, which means "hope" in Japanese. Kibo comprises six components: two research facilities -- the Pressurized Module and Exposed Facility; a Logistics Module attached to each of them; a Remote Manipulator System; and an Inter-Orbit Communication System unit. Kibo also has a scientific airlock through which experiments are transferred and exposed to the external environment of space. Kibo is Japan's first human space facility and its primary contribution to the station. Kibo will enhance the unique research capabilities of the orbiting complex by providing an additional environment in which astronauts can conduct science experiments. The various components of JEM will be assembled in space over the course of three Space Shuttle missions. The first of those three missions, STS-123, will carry the Experiment Logistics Module Pressurized Section aboard the Space Shuttle Endeavour, targeted for launch in 2007.

The Essential Genome of Escherichia coli K-12

PubMed Central

2018-01-01

ABSTRACT Transposon-directed insertion site sequencing (TraDIS) is a high-throughput method coupling transposon mutagenesis with short-fragment DNA sequencing. It is commonly used to identify essential genes. Single gene deletion libraries are considered the gold standard for identifying essential genes. Currently, the TraDIS method has not been benchmarked against such libraries, and therefore, it remains unclear whether the two methodologies are comparable. To address this, a high-density transposon library was constructed in Escherichia coli K-12. Essential genes predicted from sequencing of this library were compared to existing essential gene databases. To decrease false-positive identification of essential genes, statistical data analysis included corrections for both gene length and genome length. Through this analysis, new essential genes and genes previously incorrectly designated essential were identified. We show that manual analysis of TraDIS data reveals novel features that would not have been detected by statistical analysis alone. Examples include short essential regions within genes, orientation-dependent effects, and fine-resolution identification of genome and protein features. Recognition of these insertion profiles in transposon mutagenesis data sets will assist genome annotation of less well characterized genomes and provides new insights into bacterial physiology and biochemistry. PMID:29463657

OGEE v2: an update of the online gene essentiality database with special focus on differentially essential genes in human cancer cell lines.

PubMed

Chen, Wei-Hua; Lu, Guanting; Chen, Xiao; Zhao, Xing-Ming; Bork, Peer

2017-01-04

OGEE is an Online GEne Essentiality database. To enhance our understanding of the essentiality of genes, in OGEE we collected experimentally tested essential and non-essential genes, as well as associated gene properties known to contribute to gene essentiality. We focus on large-scale experiments, and complement our data with text-mining results. We organized tested genes into data sets according to their sources, and tagged those with variable essentiality statuses across data sets as conditionally essential genes, intending to highlight the complex interplay between gene functions and environments/experimental perturbations. Developments since the last public release include increased numbers of species and gene essentiality data sets, inclusion of non-coding essential sequences and genes with intermediate essentiality statuses. In addition, we included 16 essentiality data sets from cancer cell lines, corresponding to 9 human cancers; with OGEE, users can easily explore the shared and differentially essential genes within and between cancer types. These genes, especially those derived from cell lines that are similar to tumor samples, could reveal the oncogenic drivers, paralogous gene expression pattern and chromosomal structure of the corresponding cancer types, and can be further screened to identify targets for cancer therapy and/or new drug development. OGEE is freely available at http://ogee.medgenius.info. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Modulated Source Interferometry with Combined Amplitude and Frequency Modulation

NASA Technical Reports Server (NTRS)

Gutierrez, Roman C. (Inventor)

1998-01-01

An improved interferometer is produced by modifying a conventional interferometer to include amplitude and/or frequency modulation of a coherent light source at radio or higher frequencies. The phase of the modulation signal can be detected in an interfering beam from an interferometer and can be used to determine the actual optical phase of the beam. As such, this improvement can be adapted to virtually any two-beam interferometer, including: Michelson, Mach-Zehnder, and Sagnac interferometers. The use of an amplitude modulated coherent tight source results in an interferometer that combines the wide range advantages of coherent interferometry with the precise distance measurement advantages of white light interferometry.

Compact nanomechanical plasmonic phase modulators [Ultracompact nano-mechanical plasmonic phase modulators

DOE PAGES

Dennis, B. S.; Haftel, M. I.; Czaplewski, D. A.; ...

2015-03-30

Highly confined optical energy in plasmonic devices is advancing miniaturization in photonics. However, for mode sizes approaching ≈10 nm, the energy increasingly shifts into the metal, raising losses and hindering active phase modulation. Here, we propose a nanoelectromechanical phase-modulation principle exploiting the extraordinarily strong dependence of the phase velocity of metal–insulator–metal gap plasmons on dynamically variable gap size. We experimentally demonstrate a 23-μm-long non-resonant modulator having a 1.5π rad range, with 1.7 dB excess loss at 780 nm. Analysis shows that by simultaneously decreasing the gap, length and width, an ultracompact-footprint π rad phase modulator can be realized. This ismore » achieved without incurring the extra loss expected for plasmons confined in a decreasing gap, because the increasing phase-modulation strength from a narrowing gap offsets rising propagation losses. Here, such small, high-density electrically controllable components may find applications in optical switch fabrics and reconfigurable plasmonic optics.« less

View of damaged Apollo 13 Service Module from the Lunar/Command Modules

NASA Image and Video Library

1970-04-17

AS13-58-8464 (17 April 1970) --- This view of the severely damaged Apollo 13 Service Module (SM) was photographed from the Lunar Module/Command Module (LM/CM) following SM jettisoning. Nearest the camera is the Service Propulsion System (SPS) engine and nozzle. An entire SM panel was blown away by the apparent explosion of oxygen tank number two located in Sector 4 of the SM. The apparent rupture of the oxygen tank caused the Apollo 13 crew men to use the Lunar Module (LM) as a "lifeboat".

Modulation of learning and memory by the genetic disruption of circadian oscillator populations.

PubMed

Snider, Kaitlin H; Obrietan, Karl

2018-06-23

While a rich literature has documented that the efficiency of learning and memory varies across circadian time, a close survey of that literature reveals extensive heterogeneity in the time of day (TOD) when peak cognitive performance occurs. Moreover, most previous experiments in rodents have not focused on the question of discriminating which memory processes (e.g., working memory, memory acquisition, or retrieval) are modulated by the TOD. Here, we use assays of contextual fear conditioning and spontaneous alternation in WT (C57Bl/6 J) mice to survey circadian modulation of hippocampal-dependent memory at multiple timescales - including working memory (seconds to a few minutes), intermediate-term memory (a delay of thirty minutes), and acquisition and retrieval of long-term memory (a delay of two days). Further, in order to test the relative contributions of circadian timing mechanisms to the modulation of memory, a parallel set of studies were performed in mice lacking clock timing mechanisms. These transgenic mice lacked the essential circadian gene Bmal1, either globally (Bmal1 null) or locally (floxed Bmal1 mice which lack Bmal1 in excitatory forebrain neurons, e.g. cortical and hippocampal neurons). Here, we show that in WT mice, retrieval (but not working memory, intermediate-term memory, or acquisition of long-term memory) is modulated by TOD. However, transgenic mouse models lacking Bmal1 - both globally, and only in forebrain excitatory neurons - show deficits regardless of the memory process tested (and lack circadian modulation of retrieval). These results provide new clarity regarding the impact of TOD on hippocampal-dependent memory and support the key role of hippocampal and cortical circadian oscillations in circadian gating of cognition. Copyright © 2018. Published by Elsevier Inc.

Laser frequency modulator for modulating a laser cavity

DOEpatents

Erbert, Gaylen V.

1992-01-01

The present invention relates to a laser frequency modulator for modulating a laser cavity. It is known in the prior art to utilize a PZT (piezoelectric transducer) element in combination with a mirror to change the cavity length of a laser cavity (which changes the laser frequency). Using a PZT element to drive the mirror directly is adequate at frequencies below 10 kHz. However, in high frequency applications (100 kHz and higher) PZT elements alone do not provide a sufficient change in the cavity length. The present invention utilizes an ultrasonic concentrator with a PZT element and mirror to provide modulation of the laser cavity. With an ultrasonic concentrator, the mirror element at the end of a laser cavity can move at larger amplitudes and higher frequencies.

An ensemble framework for identifying essential proteins.

PubMed

Zhang, Xue; Xiao, Wangxin; Acencio, Marcio Luis; Lemke, Ney; Wang, Xujing

2016-08-25

Many centrality measures have been proposed to mine and characterize the correlations between network topological properties and protein essentiality. However, most of them show limited prediction accuracy, and the number of common predicted essential proteins by different methods is very small. In this paper, an ensemble framework is proposed which integrates gene expression data and protein-protein interaction networks (PINs). It aims to improve the prediction accuracy of basic centrality measures. The idea behind this ensemble framework is that different protein-protein interactions (PPIs) may show different contributions to protein essentiality. Five standard centrality measures (degree centrality, betweenness centrality, closeness centrality, eigenvector centrality, and subgraph centrality) are integrated into the ensemble framework respectively. We evaluated the performance of the proposed ensemble framework using yeast PINs and gene expression data. The results show that it can considerably improve the prediction accuracy of the five centrality measures individually. It can also remarkably increase the number of common predicted essential proteins among those predicted by each centrality measure individually and enable each centrality measure to find more low-degree essential proteins. This paper demonstrates that it is valuable to differentiate the contributions of different PPIs for identifying essential proteins based on network topological characteristics. The proposed ensemble framework is a successful paradigm to this end.

On staggered indecomposable Virasoro modules

NASA Astrophysics Data System (ADS)