Whole genome sequencing: an efficient approach to ensuring food safety

Science.gov (United States)

Lakicevic, B.; Nastasijevic, I.; Dimitrijevic, M.

2017-09-01

Whole genome sequencing is an effective, powerful tool that can be applied to a wide range of public health and food safety applications. A major difference between WGS and the traditional typing techniques is that WGS allows all genes to be included in the analysis, instead of a well-defined subset of genes or variable intergenic regions. Also, the use of WGS can facilitate the understanding of contamination/colonization routes of foodborne pathogens within the food production environment, and can also afford efficient tracking of pathogens’ entry routes and distribution from farm-to-consumer. Tracking foodborne pathogens in the food processing-distribution-retail-consumer continuum is of the utmost importance for facilitation of outbreak investigations and rapid action in controlling/preventing foodborne outbreaks. Therefore, WGS likely will replace most of the numerous workflows used in public health laboratories to characterize foodborne pathogens into one consolidated, efficient workflow.

Receptor-targeted liposome-peptide-siRNA nanoparticles represent an efficient delivery system for MRTF silencing in conjunctival fibrosis.

Science.gov (United States)

Yu-Wai-Man, Cynthia; Tagalakis, Aristides D; Manunta, Maria D; Hart, Stephen L; Khaw, Peng T

2016-02-24

There is increasing evidence that the Myocardin-related transcription factor/Serum response factor (MRTF/SRF) pathway plays a key role in fibroblast activation and that knocking down MRTF can lead to reduced scarring and fibrosis. Here, we have developed a receptor-targeted liposome-peptide-siRNA nanoparticle as a non-viral delivery system for MRTF-B siRNA in conjunctival fibrosis. Using 50 nM siRNA, the MRTF-B gene was efficiently silenced by 76% and 72% with LYR and LER nanoparticles, respectively. The silencing efficiency was low when non-targeting peptides or siRNA alone or liposome-siRNA alone were used. LYR and LER nanoparticles also showed higher silencing efficiency than PEGylated LYR-P and LER-P nanoparticles. The nanoparticles were not cytotoxic using different liposomes, targeting peptides, and 50 nM siRNA. Three-dimensional fibroblast-populated collagen matrices were also used as a functional assay to measure contraction in vitro, and showed that MRTF-B LYR nanoparticles completely blocked matrix contraction after a single transfection treatment. In conclusion, this is the first study to develop and show that receptor-targeted liposome-peptide-siRNA nanoparticles represent an efficient and safe non-viral siRNA delivery system that could be used to prevent fibrosis after glaucoma filtration surgery and other contractile scarring conditions in the eye.

A consistent and efficient graphical analysis method to improve the quantification of reversible tracer binding in radioligand receptor dynamic PET studies

OpenAIRE

Zhou, Yun; Ye, Weiguo; Brašić, James R.; Crabb, Andrew H.; Hilton, John; Wong, Dean F.

2008-01-01

The widely used Logan plot in radioligand receptor dynamic PET studies produces marked noise-induced negative biases in the estimates of total distribution volume (DVT) and binding potential (BP). To avoid the inconsistencies in the estimates from the Logan plot, a new graphical analysis method was proposed and characterized in this study. The new plot with plasma input and with reference tissue input was first derived to estimate DVT and BP. A condition was provided to ensure that the estima...

Outsourcing your medical practice call center: how to choose a vendor to ensure regulatory compliance.

Science.gov (United States)

Johnson, Bill

2014-01-01

Medical practices receive hundreds if not thousands of calls every week from patients, payers, pharmacies, and others. Outsourcing call centers can be a smart move to improve efficiency, lower costs, improve customer care, ensure proper payer management, and ensure regulatory compliance. This article discusses how to know when it's time to move to an outsourced call center, the benefits of making the move, how to choose the right call center, and how to make the transition. It also provides tips on how to manage the call center to ensure the objectives are being met.

Confinement of activating receptors at the plasma membrane controls natural killer cell tolerance.

Science.gov (United States)

Guia, Sophie; Jaeger, Baptiste N; Piatek, Stefan; Mailfert, Sébastien; Trombik, Tomasz; Fenis, Aurore; Chevrier, Nicolas; Walzer, Thierry; Kerdiles, Yann M; Marguet, Didier; Vivier, Eric; Ugolini, Sophie

2011-04-05

Natural killer (NK) cell tolerance to self is partly ensured by major histocompatibility complex (MHC) class I-specific inhibitory receptors on NK cells, which dampen their reactivity when engaged. However, NK cells that do not detect self MHC class I are not autoreactive. We used dynamic fluorescence correlation spectroscopy to show that MHC class I-independent NK cell tolerance in mice was associated with the presence of hyporesponsive NK cells in which both activating and inhibitory receptors were confined in an actin meshwork at the plasma membrane. In contrast, the recognition of self MHC class I by inhibitory receptors "educated" NK cells to become fully reactive, and activating NK cell receptors became dynamically compartmentalized in membrane nanodomains. We propose that the confinement of activating receptors at the plasma membrane is pivotal to ensuring the self-tolerance of NK cells.

Receptor-receptor interactions within receptor mosaics. Impact on neuropsychopharmacology.

Science.gov (United States)

Fuxe, K; Marcellino, D; Rivera, A; Diaz-Cabiale, Z; Filip, M; Gago, B; Roberts, D C S; Langel, U; Genedani, S; Ferraro, L; de la Calle, A; Narvaez, J; Tanganelli, S; Woods, A; Agnati, L F

2008-08-01

Future therapies for diseases associated with altered dopaminergic signaling, including Parkinson's disease, schizophrenia and drug addiction or drug dependence may substantially build on the existence of intramembrane receptor-receptor interactions within dopamine receptor containing receptor mosaics (RM; dimeric or high-order receptor oligomers) where it is believed that the dopamine D(2) receptor may operate as the 'hub receptor' within these complexes. The constitutive adenosine A(2A)/dopamine D(2) RM, located in the dorsal striato-pallidal GABA neurons, are of particular interest in view of the demonstrated antagonistic A(2A)/D(2) interaction within these heteromers; an interaction that led to the suggestion and later demonstration that A(2A) antagonists could be used as novel anti-Parkinsonian drugs. Based on the likely existence of A(2A)/D(2)/mGluR5 RM located both extrasynaptically on striato-pallidal GABA neurons and on cortico-striatal glutamate terminals, multiple receptor-receptor interactions within this RM involving synergism between A(2A)/mGluR5 to counteract D(2) signaling, has led to the proposal of using combined mGluR5 and A(2A) antagonists as a future anti-Parkinsonian treatment. Based on the same RM in the ventral striato-pallidal GABA pathways, novel strategies for the treatment of schizophrenia, building on the idea that A(2A) agonists and/or mGluR5 agonists will help reduce the increased dopaminergic signaling associated with this disease, have been suggested. Such treatment may ensure the proper glutamatergic drive from the mediodorsal thalamic nucleus to the prefrontal cortex, one which is believed to be reduced in schizophrenia due to a dominance of D(2)-like signaling in the ventral striatum. Recently, A(2A) receptors also have been shown to counteract the locomotor and sensitizing actions of cocaine and increases in A(2A) receptors have also been observed in the nucleus accumbens after extended cocaine self-administration, probably

Construction of covalently coupled, concatameric dimers of 7TM receptors

DEFF Research Database (Denmark)

Terpager, Marie; Scholl, D Jason; Kubale, Valentina

2009-01-01

-Ala repeats flanked by flexible spacers and positively charged residues to ensure correct inside-out orientation plus an extracellular HA-tag to construct covalently coupled dimers of 7TM receptors. Such 15 TM concatameric homo- and heterodimers of the beta(2)-adrenergic and the NK(1) receptors, which...... for either of the protomers, which was not observed upon simple coexpression of the two receptors. It is concluded that covalently joined 7TM receptor dimers with surprisingly normal receptor properties can be constructed with use of an artificial transmembrane connector, which perhaps can be used to fuse...

Modern Paradigm of Ensuring Competitive Advantages of an Enterprise

Directory of Open Access Journals (Sweden)

Klymchuk Alyona O.

2014-01-01

Full Text Available The article considers evolution of development of the paradigm of ensuring competitive advantages of an enterprise. Foreign and domestic scientists focus on individual directions of development of competitive advantages and pay insufficient attention to new management concepts – development of the information society, knowledge economy and dynamism of integration processes. The goal of the study is formation of the modern paradigm of ensuring competitive advantages of an enterprise with consideration of tendencies of development of the knowledge economy, information society and integration processes. Enterprise competitiveness is a synergetic characteristic, which reflects enterprise capability of dynamic response to changes of the market situation with the aim of keeping predominance over other economic subjects. Management of the future, on the basis of the management 2.0 concept, should take into account interests not only of top management and shareholders but also employees, local communities and territories and meet requirements of the society in general, individual groups of consumers and tendencies of development of managerial and information technologies. The paradigm of the modern theory of ensuring competitive advantages should include models of keeping competitive advantages in the existing markets and models of development of future markets; strategy of development of enterprise competitiveness, human capital development and efficient enterprise management.

Membrane Trafficking of Death Receptors: Implications on Signalling

Directory of Open Access Journals (Sweden)

Wulf Schneider-Brachert

2013-07-01

Full Text Available Death receptors were initially recognised as potent inducers of apoptotic cell death and soon ambitious attempts were made to exploit selective ignition of controlled cellular suicide as therapeutic strategy in malignant diseases. However, the complexity of death receptor signalling has increased substantially during recent years. Beyond activation of the apoptotic cascade, involvement in a variety of cellular processes including inflammation, proliferation and immune response was recognised. Mechanistically, these findings raised the question how multipurpose receptors can ensure selective activation of a particular pathway. A growing body of evidence points to an elegant spatiotemporal regulation of composition and assembly of the receptor-associated signalling complex. Upon ligand binding, receptor recruitment in specialized membrane compartments, formation of receptor-ligand clusters and internalisation processes constitute key regulatory elements. In this review, we will summarise the current concepts of death receptor trafficking and its implications on receptor-associated signalling events.

Means of Ensuring Information Security and Experimental Study of the Efficiency of Forensic Handwriting Techniques

OpenAIRE

Sergey Dmitrievich Kulik; Konstantin Igorevich Tkachenko; Denis Arturovich Nikonets

2013-01-01

This article deals with the special means, which allow to protect the information in the document. They are an integral part of the automated tools of ensuring the information security. It is proposed the use of a special input device PC Notes Taker. The results of experimental verification of the effectiveness of forensic handwriting techniques are described.

Cep63 and cep152 cooperate to ensure centriole duplication.

Directory of Open Access Journals (Sweden)

Nicola J Brown

Full Text Available Centrosomes consist of two centrioles embedded in pericentriolar material and function as the main microtubule organising centres in dividing animal cells. They ensure proper formation and orientation of the mitotic spindle and are therefore essential for the maintenance of genome stability. Centrosome function is crucial during embryonic development, highlighted by the discovery of mutations in genes encoding centrosome or spindle pole proteins that cause autosomal recessive primary microcephaly, including Cep63 and Cep152. In this study we show that Cep63 functions to ensure that centriole duplication occurs reliably in dividing mammalian cells. We show that the interaction between Cep63 and Cep152 can occur independently of centrosome localisation and that the two proteins are dependent on one another for centrosomal localisation. Further, both mouse and human Cep63 and Cep152 cooperate to ensure efficient centriole duplication by promoting the accumulation of essential centriole duplication factors upstream of SAS-6 recruitment and procentriole formation. These observations describe the requirement for Cep63 in maintaining centriole number in dividing mammalian cells and further establish the order of events in centriole formation.

Means of Ensuring Information Security and Experimental Study of the Efficiency of Forensic Handwriting Techniques

Directory of Open Access Journals (Sweden)

Sergey Dmitrievich Kulik

2013-06-01

Full Text Available This article deals with the special means, which allow to protect the information in the document. They are an integral part of the automated tools of ensuring the information security. It is proposed the use of a special input device PC Notes Taker. The results of experimental verification of the effectiveness of forensic handwriting techniques are described.

Canine distemper virus isolated from a monkey efficiently replicates on Vero cells expressing non-human primate SLAM receptors but not human SLAM receptor.

Science.gov (United States)

Feng, Na; Liu, Yuxiu; Wang, Jianzhong; Xu, Weiwei; Li, Tiansong; Wang, Tiecheng; Wang, Lei; Yu, Yicong; Wang, Hualei; Zhao, Yongkun; Yang, Songtao; Gao, Yuwei; Hu, Guixue; Xia, Xianzhu

2016-08-02

In 2008, an outbreak of canine distemper virus (CDV) infection in monkeys was reported in China. We isolated CDV strain (subsequently named Monkey-BJ01-DV) from lung tissue obtained from a rhesus monkey that died in this outbreak. We evaluated the ability of this virus on Vero cells expressing SLAM receptors from dog, monkey and human origin, and analyzed the H gene of Monkey-BJ01-DV with other strains. The Monkey-BJ01-DV isolate replicated to the highest titer on Vero cells expressing dog-origin SLAM (10(5.2±0.2) TCID50/ml) and monkey-origin SLAM (10(5.4±0.1) TCID50/ml), but achieved markedly lower titers on human-origin SLAM cells (10(3.3±0.3) TCID50/ml). Phylogenetic analysis of the full-length H gene showed that Monkey-BJ01-DV was highly related to other CDV strains obtained during recent CDV epidemics among species of the Canidae family in China, and these Monkey strains CDV (Monkey-BJ01-DV, CYN07-dV, Monkey-KM-01) possessed a number of amino acid specific substitutions (E276V, Q392R, D435Y and I542F) compared to the H protein of CDV epidemic in other animals at the same period. Our results suggested that the monkey origin-CDV-H protein could possess specific substitutions to adapt to the new host. Monkey-BJ01-DV can efficiently use monkey- and dog-origin SLAM to infect and replicate in host cells, but further adaptation may be required for efficient replication in host cells expressing the human SLAM receptor.

Sphingosine-1-phosphate (S1P) displays sustained S1P1 receptor agonism and signaling through S1P lyase-dependent receptor recycling.

Science.gov (United States)

Gatfield, John; Monnier, Lucile; Studer, Rolf; Bolli, Martin H; Steiner, Beat; Nayler, Oliver

2014-07-01

The sphingosine-1-phosphate (S1P) type 1 receptor (S1P1R) is a novel therapeutic target in lymphocyte-mediated autoimmune diseases. S1P1 receptor desensitization caused by synthetic S1P1 receptor agonists prevents T-lymphocyte egress from secondary lymphoid organs into the circulation. The selective S1P1 receptor agonist ponesimod, which is in development for the treatment of autoimmune diseases, efficiently reduces peripheral lymphocyte counts and displays efficacy in animal models of autoimmune disease. Using ponesimod and the natural ligand S1P, we investigated the molecular mechanisms leading to different signaling, desensitization and trafficking behavior of S1P1 receptors. In recombinant S1P1 receptor-expressing cells, ponesimod and S1P triggered Gαi protein-mediated signaling and β-arrestin recruitment with comparable potency and efficiency, but only ponesimod efficiently induced intracellular receptor accumulation. In human umbilical vein endothelial cells (HUVEC), ponesimod and S1P triggered translocation of the endogenous S1P1 receptor to the Golgi compartment. However, only ponesimod treatment caused efficient surface receptor depletion, receptor accumulation in the Golgi and degradation. Impedance measurements in HUVEC showed that ponesimod induced only short-lived Gαi protein-mediated signaling followed by resistance to further stimulation, whereas S1P induced sustained Gαi protein-mediated signaling without desensitization. Inhibition of S1P lyase activity in HUVEC rendered S1P an efficient S1P1 receptor internalizing compound and abrogated S1P-mediated sustained signaling. This suggests that S1P lyase - by facilitating S1P1 receptor recycling - is essential for S1P-mediated sustained signaling, and that synthetic agonists are functional antagonists because they are not S1P lyase substrates. Copyright © 2014 Elsevier Inc. All rights reserved.

In vitro assessment of attachment pattern and replication efficiency of H5N1 influenza A viruses with altered receptor specificity

NARCIS (Netherlands)

S. Chutinimitkul (Salin); D.A.J. van Riel (Debby); V.J. Munster (Vincent); J.M.A. van den Brand (Judith); G.F. Rimmelzwaan (Guus); T. Kuiken (Thijs); A.D.M.E. Osterhaus (Albert); R.A.M. Fouchier (Ron); E. de Wit (Emmie)

2010-01-01

textabstractThe continuous circulation of the highly pathogenic avian influenza (HPAI) H5N1 virus has been a cause of great concern. The possibility of this virus acquiring specificity for the human influenza A virus receptor, α2,6-linked sialic acids (SA), and being able to transmit efficiently

A monomeric G protein-coupled receptor isolated in a high-density lipoprotein particle efficiently activates its G protein

DEFF Research Database (Denmark)

Whorton, Matthew R; Bokoch, Michael P; Rasmussen, Søren Gøgsig Faarup

2007-01-01

G protein-coupled receptors (GPCRs) respond to a diverse array of ligands, mediating cellular responses to hormones and neurotransmitters, as well as the senses of smell and taste. The structures of the GPCR rhodopsin and several G proteins have been determined by x-ray crystallography, yet...... the organization of the signaling complex between GPCRs and G proteins is poorly understood. The observations that some GPCRs are obligate heterodimers, and that many GPCRs form both homo- and heterodimers, has led to speculation that GPCR dimers may be required for efficient activation of G proteins. However......, technical limitations have precluded a definitive analysis of G protein coupling to monomeric GPCRs in a biochemically defined and membrane-bound system. Here we demonstrate that a prototypical GPCR, the beta2-adrenergic receptor (beta2AR), can be incorporated into a reconstituted high-density lipoprotein...

In vitro assessment of attachment pattern and replication efficiency of H5N1 influenza A viruses with altered receptor specificity.

Science.gov (United States)

Chutinimitkul, Salin; van Riel, Debby; Munster, Vincent J; van den Brand, Judith M A; Rimmelzwaan, Guus F; Kuiken, Thijs; Osterhaus, Albert D M E; Fouchier, Ron A M; de Wit, Emmie

2010-07-01

The continuous circulation of the highly pathogenic avian influenza (HPAI) H5N1 virus has been a cause of great concern. The possibility of this virus acquiring specificity for the human influenza A virus receptor, alpha2,6-linked sialic acids (SA), and being able to transmit efficiently among humans is a constant threat to human health. Different studies have described amino acid substitutions in hemagglutinin (HA) of clinical HPAI H5N1 isolates or that were introduced experimentally that resulted in an increased, but not exclusive, binding of these virus strains to alpha2,6-linked SA. We introduced all previously described amino acid substitutions and combinations thereof into a single genetic background, influenza virus A/Indonesia/5/05 HA, and tested the receptor specificity of these 27 mutant viruses. The attachment pattern to ferret and human tissues of the upper and lower respiratory tract of viruses with alpha2,6-linked SA receptor preference was then determined and compared to the attachment pattern of a human influenza A virus (H3N2). At least three mutant viruses showed an attachment pattern to the human respiratory tract similar to that of the human H3N2 virus. Next, the replication efficiencies of these mutant viruses and the effects of three different neuraminidases on virus replication were determined. These data show that influenza virus A/Indonesia/5/05 potentially requires only a single amino acid substitution to acquire human receptor specificity, while at the same time remaining replication competent, thus suggesting that the pandemic threat posed by HPAI H5N1 is far from diminished.

In Vitro Assessment of Attachment Pattern and Replication Efficiency of H5N1 Influenza A Viruses with Altered Receptor Specificity▿

Science.gov (United States)

Chutinimitkul, Salin; van Riel, Debby; Munster, Vincent J.; van den Brand, Judith M. A.; Rimmelzwaan, Guus F.; Kuiken, Thijs; Osterhaus, Albert D. M. E.; Fouchier, Ron A. M.; de Wit, Emmie

2010-01-01

The continuous circulation of the highly pathogenic avian influenza (HPAI) H5N1 virus has been a cause of great concern. The possibility of this virus acquiring specificity for the human influenza A virus receptor, α2,6-linked sialic acids (SA), and being able to transmit efficiently among humans is a constant threat to human health. Different studies have described amino acid substitutions in hemagglutinin (HA) of clinical HPAI H5N1 isolates or that were introduced experimentally that resulted in an increased, but not exclusive, binding of these virus strains to α2,6-linked SA. We introduced all previously described amino acid substitutions and combinations thereof into a single genetic background, influenza virus A/Indonesia/5/05 HA, and tested the receptor specificity of these 27 mutant viruses. The attachment pattern to ferret and human tissues of the upper and lower respiratory tract of viruses with α2,6-linked SA receptor preference was then determined and compared to the attachment pattern of a human influenza A virus (H3N2). At least three mutant viruses showed an attachment pattern to the human respiratory tract similar to that of the human H3N2 virus. Next, the replication efficiencies of these mutant viruses and the effects of three different neuraminidases on virus replication were determined. These data show that influenza virus A/Indonesia/5/05 potentially requires only a single amino acid substitution to acquire human receptor specificity, while at the same time remaining replication competent, thus suggesting that the pandemic threat posed by HPAI H5N1 is far from diminished. PMID:20392847

Ensuring Energy Efficient 5G User Equipment by Technology Evolution and Reuse

DEFF Research Database (Denmark)

Lauridsen, Mads; Berardinelli, Gilberto; Sørensen, Troels Bundgaard

2014-01-01

the features’ pros and cons in achieving high performance in terms of data rate and/or latency while limiting their effect on the UE power consumption. Based on the discussion we give general recommendations for an energy efficient 5G design in the context of a previously proposed RAT concept.......Research on fifth generation (5G) radio access technology (RAT) is ramping up, with the goal of significantly improving user data rates and latency compared to previous radio generations. While energy efficiency (EE) of the user equipment (UE) was not a key optimization parameter for the current...... standards, it is anticipated to become a distinguishing factor for 5G. In this paper, we analyze established and emerging technological solutions for features such as waveform, frame structure, duplexing and multiple antenna transmission from an EE perspective. Our contribution is to identify and discuss...

Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication.

Directory of Open Access Journals (Sweden)

Eveline Kindler

2017-02-01

Full Text Available Coronaviruses are of veterinary and medical importance and include highly pathogenic zoonotic viruses, such as SARS-CoV and MERS-CoV. They are known to efficiently evade early innate immune responses, manifesting in almost negligible expression of type-I interferons (IFN-I. This evasion strategy suggests an evolutionary conserved viral function that has evolved to prevent RNA-based sensing of infection in vertebrate hosts. Here we show that the coronavirus endonuclease (EndoU activity is key to prevent early induction of double-stranded RNA (dsRNA host cell responses. Replication of EndoU-deficient coronaviruses is greatly attenuated in vivo and severely restricted in primary cells even during the early phase of the infection. In macrophages we found immediate induction of IFN-I expression and RNase L-mediated breakdown of ribosomal RNA. Accordingly, EndoU-deficient viruses can retain replication only in cells that are deficient in IFN-I expression or sensing, and in cells lacking both RNase L and PKR. Collectively our results demonstrate that the coronavirus EndoU efficiently prevents simultaneous activation of host cell dsRNA sensors, such as Mda5, OAS and PKR. The localization of the EndoU activity at the site of viral RNA synthesis-within the replicase complex-suggests that coronaviruses have evolved a viral RNA decay pathway to evade early innate and intrinsic antiviral host cell responses.

BP Network Control for Resource Allocation and QoS Ensurance in UAV Cloud

Directory of Open Access Journals (Sweden)

Ang Gao

2018-01-01

Full Text Available Unmanned aerial vehicle (UAV cloud can greatly enhance the intelligence of unmanned systems by dynamically unloading the compute-intensive applications to cloud. For the uncertain nature of UAV missions and fast-changing environment, different UAV applications may have different quality of service (QoS requirements. This paper proposes a mixed QoS ensurance and energy-balanced (MQEB architecture for UAV cloud from a view of control theory, which can support both hard and soft QoS ensurance with the consideration of energy saving. The hard and soft QoS requirements are decoupled by being normalized into a two-level cascaded feedback loop. The former is time slot loop (TS-Loop to enforce the absolute QoS ensurance for real-time applications, and the latter is contention window loop (CW-Loop to enforce the plastic QoS ensurance for non-real-time applications. Finally, the back propagating (BP neuron network is used for parameters’ self-tuning and controller design. The hardware experiments demonstrate the feasibility of MQEB. In heavy load, MQEB has greater throughput and better energy efficiency, and in light load, MQBE has lower total power consumption.

Design principles of nuclear receptor signaling: how complex networking improves signal transduction

Science.gov (United States)

Kolodkin, Alexey N; Bruggeman, Frank J; Plant, Nick; Moné, Martijn J; Bakker, Barbara M; Campbell, Moray J; van Leeuwen, Johannes P T M; Carlberg, Carsten; Snoep, Jacky L; Westerhoff, Hans V

2010-01-01

The topology of nuclear receptor (NR) signaling is captured in a systems biological graphical notation. This enables us to identify a number of ‘design' aspects of the topology of these networks that might appear unnecessarily complex or even functionally paradoxical. In realistic kinetic models of increasing complexity, calculations show how these features correspond to potentially important design principles, e.g.: (i) cytosolic ‘nuclear' receptor may shuttle signal molecules to the nucleus, (ii) the active export of NRs may ensure that there is sufficient receptor protein to capture ligand at the cytoplasmic membrane, (iii) a three conveyor belts design dissipating GTP-free energy, greatly aids response, (iv) the active export of importins may prevent sequestration of NRs by importins in the nucleus and (v) the unspecific nature of the nuclear pore may ensure signal-flux robustness. In addition, the models developed are suitable for implementation in specific cases of NR-mediated signaling, to predict individual receptor functions and differential sensitivity toward physiological and pharmacological ligands. PMID:21179018

DETERMINATION OF THE OPTIMAL CAPITAL INVESTMENTS TO ENSURE THE SUSTAINABLE DEVELOPMENT OF THE RAILWAY

Directory of Open Access Journals (Sweden)

O. I. Kharchenko

2015-04-01

Full Text Available Purpose. Every year more attention is paid for the theoretical and practical issue of sustainable development of railway transport. But today the mechanisms of financial support of this development are poorly understood. Therefore, the aim of this article is to determine the optimal investment allocation to ensure sustainable development of the railway transport on the example of State Enterprise «Prydniprovsk Railway» and the creation of preconditions for the mathematical model development. Methodology. The ensuring task for sustainable development of railway transport is solved on the basis of the integral indicator of sustainable development effectiveness and defined as the maximization of this criterion. The optimization of measures technological and technical characters are proposed to carry out for increasing values of the integral performance measure components. To the optimization activities of technological nature that enhance the performance criteria belongs: optimization of the number of train and shunting locomotives, optimization of power handling mechanisms at the stations, optimization of routes of train flows. The activities related to the technical nature include: modernization of railways in the direction of their electrification and modernization of the running gear and coupler drawbars of rolling stock, as well as means of separators mechanization at stations to reduce noise impacts on the environment. Findings. The work resulted in the optimal allocation of investments to ensure the sustainable development of railway transportation of State Enterprise «Prydniprovsk Railway». This allows providing such kind of railway development when functioning of State Enterprise «Prydniprovsk Railway» is characterized by a maximum value of the integral indicator of efficiency. Originality. The work was reviewed and the new approach was proposed to determine the optimal allocation of capital investments to ensure sustainable

Energy and Water Efficiency on Campus | NREL

Science.gov (United States)

Energy and Water Efficiency on Campus Energy and Water Efficiency on Campus NREL ensures the resiliency of our future energy and water systems through energy efficiency strategies and technologies , renewable energy, and water efficiency on the NREL campus. FY17 Energy Intensity. The South Table Mountain

Investing in Nurses is a Prerequisite for Ensuring Universal Health Coverage.

Science.gov (United States)

Kurth, Ann E; Jacob, Sheena; Squires, Allison P; Sliney, Anne; Davis, Sheila; Stalls, Suzanne; Portillo, Carmen J

2016-01-01

Nurses and midwives constitute the majority of the global health workforce and the largest health care expenditure. Efficient production, successful deployment, and ongoing retention based on carefully constructed policies regarding the career opportunities of nurses, midwives, and other providers in health care systems are key to ensuring universal health coverage. Yet nurses are constrained by practice regulations, workplaces, and career ladder barriers from contributing to primary health care delivery. Evidence shows that quality HIV care, comparable to that of physicians, is provided by trained nurses and associate clinicians, but many African countries' health systems remain dependent on limited numbers of physicians and fail to meet the demand for treatment. The World Health Organization endorses task sharing to ensure universal health coverage in HIV and maternal health, which requires an investment in nursing education, retention, and professional growth opportunities. Exemplars from Haiti, Rwanda, Republic of Georgia, and multi-country efforts are described. Copyright © 2016 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

M3 muscarinic receptor interaction with phospholipase C beta3 determines its signaling efficiency

NARCIS (Netherlands)

Kan, W.; Adjobo-Hermans, M.J.; Burroughs, M.; Faibis, G.; Malik, S.; Tall, G.G.; Smrcka, A.V.

2014-01-01

Phospholipase Cbeta (PLCbeta) enzymes are activated by G protein-coupled receptors through receptor-catalyzed guanine nucleotide exchange on Galphabetagamma heterotrimers containing Gq family G proteins. Here we report evidence for a direct interaction between M3 muscarinic receptor (M3R) and

Human orexin/hypocretin receptors form constitutive homo- and heteromeric complexes with each other and with human CB1 cannabinoid receptors

International Nuclear Information System (INIS)

Jäntti, Maria H.; Mandrika, Ilona; Kukkonen, Jyrki P.

2014-01-01

Highlights: • OX 1 and OX 2 orexin and CB 1 cannabinoid receptor dimerization was investigated. • Bioluminescence resonance energy transfer method was used. • All receptors readily formed constitutive homo- and heteromeric complexes. - Abstract: Human OX 1 orexin receptors have been shown to homodimerize and they have also been suggested to heterodimerize with CB 1 cannabinoid receptors. The latter has been suggested to be important for orexin receptor responses and trafficking. In this study, we wanted to assess the ability of the other combinations of receptors to also form similar complexes. Vectors for expression of human OX 1 , OX 2 and CB 1 receptors, C-terminally fused with either Renilla luciferase or GFP 2 green fluorescent protein variant, were generated. The constructs were transiently expressed in Chinese hamster ovary cells, and constitutive dimerization between the receptors was assessed by bioluminescence energy transfer (BRET). Orexin receptor subtypes readily formed homo- and hetero(di)mers, as suggested by significant BRET signals. CB 1 receptors formed homodimers, and they also heterodimerized with both orexin receptors. Interestingly, BRET efficiency was higher for homodimers than for almost all heterodimers. This is likely to be due to the geometry of the interaction; the putatively symmetric dimers may place the C-termini in a more suitable orientation in homomers. Fusion of luciferase to an orexin receptor and GFP 2 to CB 1 produced more effective BRET than the opposite fusions, also suggesting differences in geometry. Similar was seen for the OX 1 –OX 2 interaction. In conclusion, orexin receptors have a significant propensity to make homo- and heterodi-/oligomeric complexes. However, it is unclear whether this affects their signaling. As orexin receptors efficiently signal via endocannabinoid production to CB 1 receptors, dimerization could be an effective way of forming signal complexes with optimal cannabinoid concentrations

Dietary Sodium Suppresses Digestive Efficiency via the Renin-Angiotensin System.

Science.gov (United States)

Weidemann, Benjamin J; Voong, Susan; Morales-Santiago, Fabiola I; Kahn, Michael Z; Ni, Jonathan; Littlejohn, Nicole K; Claflin, Kristin E; Burnett, Colin M L; Pearson, Nicole A; Lutter, Michael L; Grobe, Justin L

2015-06-11

Dietary fats and sodium are both palatable and are hypothesized to synergistically contribute to ingestive behavior and thereby obesity. Contrary to this hypothesis, C57BL/6J mice fed a 45% high fat diet exhibited weight gain that was inhibited by increased dietary sodium content. This suppressive effect of dietary sodium upon weight gain was mediated specifically through a reduction in digestive efficiency, with no effects on food intake behavior, physical activity, or resting metabolism. Replacement of circulating angiotensin II levels reversed the effects of high dietary sodium to suppress digestive efficiency. While the AT1 receptor antagonist losartan had no effect in mice fed low sodium, the AT2 receptor antagonist PD-123,319 suppressed digestive efficiency. Correspondingly, genetic deletion of the AT2 receptor in FVB/NCrl mice resulted in suppressed digestive efficiency even on a standard chow diet. Together these data underscore the importance of digestive efficiency in the pathogenesis of obesity, and implicate dietary sodium, the renin-angiotensin system, and the AT2 receptor in the control of digestive efficiency regardless of mouse strain or macronutrient composition of the diet. These findings highlight the need for greater understanding of nutrient absorption control physiology, and prompt more uniform assessment of digestive efficiency in animal studies of energy balance.

Distributed Control to Ensure Proportional Load Sharing and Improve Voltage Regulation in Low-Voltage DC Microgrids

DEFF Research Database (Denmark)

Anand, Sandeep; G. Fernandes, Baylon; Guerrero, Josep M.

2013-01-01

DC microgrids are gaining popularity due to high efficiency, high reliability, and easy interconnection of renewable sources as compared to the ac system. Control objectives of dc microgrid are: 1) to ensure equal load sharing (in per unit) among sources; and 2) to maintain low-voltage regulation...

Epithelial-microbial crosstalk in polymeric Ig receptor deficient mice

NARCIS (Netherlands)

Reikvam, D.H.; Derrien, M.M.N.; Islam, R.; Erofeev, A.; Grcic, V.; Sandvik, A.; Gaustad, P.; Meza-Zepeda, L.A.; Jahnsen, F.L.; Smidt, H.; Johansen, F.E.

2012-01-01

Innate and adaptive mucosal defense mechanisms ensure a homeostatic relationship with the large and complex mutualistic gut microbiota. Dimeric IgA and pentameric IgM are transported across the intestinal epithelium via the epithelial polymeric Ig receptor (pIgR) and provide a significant portion of

The photonic nanowire: A highly efficient single-photon source

DEFF Research Database (Denmark)

Gregersen, Niels

2014-01-01

The photonic nanowire represents an attractive platform for a quantum light emitter. However, careful optical engineering using the modal method, which elegantly allows access to all relevant physical parameters, is crucial to ensure high efficiency.......The photonic nanowire represents an attractive platform for a quantum light emitter. However, careful optical engineering using the modal method, which elegantly allows access to all relevant physical parameters, is crucial to ensure high efficiency....

THE ISSUEOFSTRENGTHENING BUDGET CAPACITY FOR ENSURING THE FINANCIALINDEPENDENCE OFLOCALAUTHORITIES

Directory of Open Access Journals (Sweden)

Dmytriy V. Nekhaychuk

2018-05-01

Full Text Available The paper deals with the issues on strengthening local governments’ budget capacity in the face of modern challenges. It shows the conceptual in-depth study of local budgets foundations, income and practical recommendations focusing on stability and capacity. The author proves that the revenues of local budgets play a crucial role in ensuring the full and effective performance of the functions and local authorities’ tasks. The paper shows the scientific analysis of modern economists’ views on the local authorities’ financial autonomy and the local budgets’ role in the process. The paper also shows the retrospective comparative analysis of methods, used by local and foreign scientists for the formation of local budgets’ revenues. It considers the economic nature of income in local budgets as a source of finance, ensures the efficient operation of local authorities. It has been found out that the organization of the process of forming local budgets’ revenues is influenced by the organizational and legal forms of management, type of ownership and specifics of enterprises. Taxes are the dominant source of local budgets’ incomes, the financial regulator of production, means of ensuring socio-economic development of the separate administrative and territorial units and the state as a whole. The authors also analyze different types of revenues, including tax, in the revenue part of local budgets. The authors propose to expand the list of local taxes and fees due to the introduction of tax with targeted use of received funds. The conceptual basis of financial independence of local self-government lies in in the optimal interests of the population, local government, state and business structures. The increase of own revenues in the share of local budgets becomes a strategic issue of the financial autonomy and the corresponding administrative and territorial units.

Efficient cell-free production of olfactory receptors: detergent optimization, structure, and ligand binding analyses.

Science.gov (United States)

Kaiser, Liselotte; Graveland-Bikker, Johanna; Steuerwald, Dirk; Vanberghem, Mélanie; Herlihy, Kara; Zhang, Shuguang

2008-10-14

High-level production of membrane proteins, particularly of G protein-coupled receptors (GPCRs) in heterologous cell systems encounters a number of difficulties from their inherent hydrophobicity in their transmembrane domains, which frequently cause protein aggregation and cytotoxicity and thus reduce the protein yield. Recent advances in cell-free protein synthesis circumvent those problems to produce membrane proteins with a yield sometimes exceeding the cell-based approach. Here, we report cell-free production of a human olfactory receptor 17-4 (hOR17-4) using the wheat germ extract. Using the simple method, we also successful produced two additional olfactory receptors. To obtain soluble olfactory receptors and to increase yield, we directly added different detergents in varying concentrations to the cell-free reaction. To identify a purification buffer system that maintained the receptor in a nonaggregated form, we developed a method that uses small-volume size-exclusion column chromatography combined with rapid and sensitive dot-blot detection. Different buffer components including salt concentration, various detergents and detergent concentration, and reducing agent and its concentrations were evaluated for their ability to maintain the cell-free produced protein stable and nonaggregated. The purified olfactory receptor displays a typical a alpha-helical CD spectrum. Surface plasmon resonance measurements were used to show binding of a known ligand undecanal to hOR17-4. Our approach to produce a high yield of purified olfactory receptor is a milestone toward obtaining a large quantity of olfactory receptors for designing bionic sensors. Furthermore, this simple approach may be broadly useful not only for other classes of GPCRs but also for other membrane proteins.

Modelling the System of Ensuring the Investment Security

Directory of Open Access Journals (Sweden)

Moroz Maxim O.

2017-11-01

Full Text Available The article explores approaches to modelling the system of ensuring the investment security. Necessity of observance of investment security of Ukraine has been substantiated. The author’s own vision of the modelling essentials has been provided. The eligibility for consideration of the system of ensuring the investment security of Ukraine in the functional, structural, process, formative, and factor aspects has been proved. The target setting and tasks of a functional model of the system of ensuring the investment security have been defined. The functions, subjects, organizational-economic mechanisms of the system of ensuring the investment security of Ukraine have been characterized. A structural model of the system of ensuring the investment security has been presented. Special attention has been given to the definition of objects of direct and indirect influence, control and controlled subsystems, aggregate of indicators, safe levels, principles of formation of the investment security system. The process and formative models of the system of ensuring the investment security, as well as the algorithm of the complex assessment of the level of investment security, were analyzed in detail. Measures to ensure the investment security of Ukraine have been defined.

Hindbrain ghrelin receptor signaling is sufficient to maintain fasting glucose.

Directory of Open Access Journals (Sweden)

Michael M Scott

Full Text Available The neuronal coordination of metabolic homeostasis requires the integration of hormonal signals with multiple interrelated central neuronal circuits to produce appropriate levels of food intake, energy expenditure and fuel availability. Ghrelin, a peripherally produced peptide hormone, circulates at high concentrations during nutrient scarcity. Ghrelin promotes food intake, an action lost in ghrelin receptor null mice and also helps maintain fasting blood glucose levels, ensuring an adequate supply of nutrients to the central nervous system. To better understand mechanisms of ghrelin action, we have examined the roles of ghrelin receptor (GHSR expression in the mouse hindbrain. Notably, selective hindbrain ghrelin receptor expression was not sufficient to restore ghrelin-stimulated food intake. In contrast, the lowered fasting blood glucose levels observed in ghrelin receptor-deficient mice were returned to wild-type levels by selective re-expression of the ghrelin receptor in the hindbrain. Our results demonstrate the distributed nature of the neurons mediating ghrelin action.

Human orexin/hypocretin receptors form constitutive homo- and heteromeric complexes with each other and with human CB{sub 1} cannabinoid receptors

Energy Technology Data Exchange (ETDEWEB)

Jäntti, Maria H., E-mail: maria.jantti@helsinki.fi [Department of Veterinary Biosciences, POB 66, FIN-00014 University of Helsinki (Finland); Mandrika, Ilona, E-mail: ilona@biomed.lu.lv [Latvian Biomedical Research and Study Centre, Ratsupites Str. 1, Riga LV 1067 (Latvia); Kukkonen, Jyrki P., E-mail: jyrki.kukkonen@helsinki.fi [Department of Veterinary Biosciences, POB 66, FIN-00014 University of Helsinki (Finland)

2014-03-07

Highlights: • OX{sub 1} and OX{sub 2} orexin and CB{sub 1} cannabinoid receptor dimerization was investigated. • Bioluminescence resonance energy transfer method was used. • All receptors readily formed constitutive homo- and heteromeric complexes. - Abstract: Human OX{sub 1} orexin receptors have been shown to homodimerize and they have also been suggested to heterodimerize with CB{sub 1} cannabinoid receptors. The latter has been suggested to be important for orexin receptor responses and trafficking. In this study, we wanted to assess the ability of the other combinations of receptors to also form similar complexes. Vectors for expression of human OX{sub 1}, OX{sub 2} and CB{sub 1} receptors, C-terminally fused with either Renilla luciferase or GFP{sup 2} green fluorescent protein variant, were generated. The constructs were transiently expressed in Chinese hamster ovary cells, and constitutive dimerization between the receptors was assessed by bioluminescence energy transfer (BRET). Orexin receptor subtypes readily formed homo- and hetero(di)mers, as suggested by significant BRET signals. CB{sub 1} receptors formed homodimers, and they also heterodimerized with both orexin receptors. Interestingly, BRET efficiency was higher for homodimers than for almost all heterodimers. This is likely to be due to the geometry of the interaction; the putatively symmetric dimers may place the C-termini in a more suitable orientation in homomers. Fusion of luciferase to an orexin receptor and GFP{sup 2} to CB{sub 1} produced more effective BRET than the opposite fusions, also suggesting differences in geometry. Similar was seen for the OX{sub 1}–OX{sub 2} interaction. In conclusion, orexin receptors have a significant propensity to make homo- and heterodi-/oligomeric complexes. However, it is unclear whether this affects their signaling. As orexin receptors efficiently signal via endocannabinoid production to CB{sub 1} receptors, dimerization could be an effective way

ITAM-like signalling for efficient phagocytosis : The paradigm of the granulocyte receptor CEACAM3

OpenAIRE

Pils, Stefan

2010-01-01

Human CEACAM3 is a tailor-made receptor of the innate immune system to fight pathogens exploiting epithelial CEACAM-family members for colonisation and invasion of their host. Previous studies established CEACAM3 as the receptor facilitating rapid phagocytosis and elimination of N. gonorrhoeae by human granulocytes. The studies reported here set out to shed light on the evolution of this highly specialised receptor and the associated signalling machinery.CEACAM3 arose from exon shuffling afte...

Model of Formation of the Enterprise Business Portfolio in the Context of Ensuring Strategic Flexibility

Directory of Open Access Journals (Sweden)

Shatilova Olena V.

2014-01-01

Full Text Available The article considers urgent problems of enterprise management under conditions of external environment instability, studies problems of the enterprise strategic flexibility management. It shows that one of the efficient mechanisms of ensuring strategic flexibility is restructuring of the enterprise business portfolio in accordance with the change of the situation in the target market of enterprise functioning. The goal of the article is development of a model of formation of enterprise business portfolio in the context of ensuring strategic flexibility. The main method of optimisation of the enterprise business portfolio in the context of ensuring strategic flexibility is the use of modification of the Markowitz model of investment portfolio formation. The offered model of the enterprise business portfolio formation allows taking into account changes of external and internal environments and conducting portfolio restructuring in the event of the change of the enterprise target market situation. Prospects of further studies in this direction are detailed elaboration and formalisation of the organisational and economic mechanism of realisation of strategic flexibility at an enterprise.

N-glycosylation of the β2 adrenergic receptor regulates receptor function by modulating dimerization.

Science.gov (United States)

Li, Xiaona; Zhou, Mang; Huang, Wei; Yang, Huaiyu

2017-07-01

N-glycosylation is a common post-translational modification of G-protein-coupled receptors (GPCRs). However, it remains unknown how N-glycosylation affects GPCR signaling. β 2 adrenergic receptor (β 2 AR) has three N-glycosylation sites: Asn6, Asn15 at the N-terminus, and Asn187 at the second extracellular loop (ECL2). Here, we show that deletion of the N-glycan did not affect receptor expression and ligand binding. Deletion of the N-glycan at the N-terminus rather than Asn187 showed decreased effects on isoproterenol-promoted G-protein-dependent signaling, β-arrestin2 recruitment, and receptor internalization. Both N6Q and N15Q showed decreased receptor dimerization, while N187Q did not influence receptor dimerization. As decreased β 2 AR homodimer accompanied with reduced efficiency for receptor function, we proposed that the N-glycosylation of β 2 AR regulated receptor function by influencing receptor dimerization. To verify this hypothesis, we further paid attention to the residues at the dimerization interface. Studies of Lys60 and Glu338, two residues at the receptor dimerization interface, exhibited that the K60A/E338A showed decreased β 2 AR dimerization and its effects on receptor signaling were similar to N6Q and N15Q, which further supported the importance of receptor dimerization for receptor function. This work provides new insights into the relationship among glycosylation, dimerization, and function of GPCRs. Peptide-N-glycosidase F (PNGase F, EC 3.2.2.11); endo-β-N-acetylglucosaminidase A (Endo-A, EC 3.2.1.96). © 2017 Federation of European Biochemical Societies.

Negative regulation of Toll-like receptor signalling 

Directory of Open Access Journals (Sweden)

Halina Antosz

2013-04-01

Full Text Available The mechanism of innate immunity is based on the pattern recognition receptors (PRR that recognize molecular patterns associated with pathogens (PAMPs. Among PRR receptors Toll-like receptors (TLR are distinguished. As a result of contact with pathogens, TLRs activate specific intracellular signaling pathways. It happens through proteins such as adaptor molecules, e.g. MyD88, TIRAP, TRIF, TRAM, and IPS-1, which participate in the cascade activation of kinases (IKK, MAP, RIP-1, TBK-1 as well as transcription factors (NF-κB, AP-1 and regulatory factor (IRF3. The result of this activation is the production of active proinflammatory cytokines, chemokines, interferons and enzymes. The PRR pathways are controlled by extra – and intracellular molecules to prevent overexpression of PRR. They include soluble receptors (sTLR, transmembrane proteins (ST2, SIGIRR, RP105, TRAIL-R and intracellular inhibitors (SOCS-1, SOCS-3, sMyD88, TOLLIP, IRAK-M, SARM, A20, β-arrestin, CYLD, SHP. These molecules maintain the balance between activation and inhibition and ensure balancing of the beneficial and adverse effects of antigen recognition.

Towards ensuring gender equity.

Science.gov (United States)

Basu, A

1996-01-01

All people should participate in the development process. Many, however, remain excluded from the benefits of development. For example, women are privy to only a small share of developmental opportunities. The goals of equality, development, and peace were stated during the Fourth World Conference on Women held in Beijing in September 1995. The author considers whether women truly have equitable access to literacy, education, food, nutrition, health, employment, and the political and economic decision making process. She stresses that the goals pronounced at the Fourth World Conference on Women must be backed up with the necessary resources, including institutions established at the local, state, and national levels to ensure that the objectives are implemented and the implementation is monitored. The author further argues that in order for women to achieve equality with men, all girls must have access to primary and secondary schools; basic literacy is inadequate. Moreover, gender stereotyping must be avoided and gender sensitization ensured at all levels.

Human NKG2D-ligands: cell biology strategies to ensure immune recognition

Directory of Open Access Journals (Sweden)

Lola eFernández-Messina

2012-09-01

Full Text Available Immune recognition mediated by the activating receptor NKG2D plays an important role for the elimination of stressed cells, including tumours and virus-infected cells. On the other hand, the ligands for NKG2D can also be shed into the sera of cancer patients where they weaken the immune response by downmodulating the receptor on effector cells, mainly NK and T cells. Although both families of NKG2D-ligands, MICA/B and ULBPs, are related to MHC molecules and their expression is increased after stress, many differences are observed in terms of their biochemical properties and cell trafficking. In this paper, we summarise the variety of NKG2D-ligands and propose that selection pressure has driven evolution of diversity in their trafficking and shedding, but not receptor binding affinity. However, it is also possible to identify functional properties common to individual ULBP molecules and MICA/B alleles, but not generally conserved within the MIC or ULBP families. These characteristics likely represent examples of convergent evolution for efficient immune recognition, but are also attractive targets for pathogen immune evasion strategies. Categorization of NKG2D-ligands according to their biological features, rather than their genetic family, may help to achieve a better understanding of NKG2D-ligand association with disease.

A Dual-Sensing Receptor Confers Robust Cellular Homeostasis

Directory of Open Access Journals (Sweden)

Hannah Schramke

2016-06-01

Full Text Available Cells have evolved diverse mechanisms that maintain intracellular homeostasis in fluctuating environments. In bacteria, control is often exerted by bifunctional receptors acting as both kinase and phosphatase to regulate gene expression, a design known to provide robustness against noise. Yet how such antagonistic enzymatic activities are balanced as a function of environmental change remains poorly understood. We find that the bifunctional receptor that regulates K+ uptake in Escherichia coli is a dual sensor, which modulates its autokinase and phosphatase activities in response to both extracellular and intracellular K+ concentration. Using mathematical modeling, we show that dual sensing is a superior strategy for ensuring homeostasis when both the supply of and demand for a limiting resource fluctuate. By engineering standards, this molecular control system displays a strikingly high degree of functional integration, providing a reference for the vast numbers of receptors for which the sensing strategy remains elusive.

Cetuximab in combination with anti-human IgG antibodies efficiently down-regulates the EGF receptor by macropinocytosis

International Nuclear Information System (INIS)

Berger, Christian; Madshus, Inger Helene; Stang, Espen

2012-01-01

The monoclonal antibody C225 (Cetuximab) blocks binding of ligand to the epidermal growth factor receptor (EGFR). In addition, it is known that incubation with C225 induces endocytosis of the EGFR. This endocytosis has previously been shown to be increased when C225 is combined with an additional monoclonal anti-EGFR antibody. However, the effects of antibody combinations on EGFR activation, endocytosis, trafficking and degradation have been unclear. By binding a secondary antibody to the C225-EGFR complex, we here demonstrate that a combination of antibodies can efficiently internalize and degrade the EGFR. Although the combination of antibodies activated the EGFR kinase and induced ubiquitination of the EGFR, the kinase activity was not required for internalization of the EGFR. In contrast to EGF-induced EGFR down-regulation, the antibody combination efficiently degraded the EGFR without initiating downstream proliferative signaling. The antibody-induced internalization of EGFR was found not to depend on clathrin and/or dynamin, but depended on actin polymerization, suggesting induction of macropinocytosis. Macropinocytosis may cause internalization of large membrane areas, and this could explain the highly efficient internalization of the EGFR induced by combination of antibodies. -- Highlight: ► Cetuximab induced endocytosis of EGFR increases upon combination with anti-human IgG. ► Antibody combination causes internalization of EGFR by macropinocytosis. ► Antibody-induced internalization of EGFR is independent of EGFR kinase activity. ► Antibody combination may have a zipper effect and cross-link EGFRs on neighboring cells.

Molecular analysis of the nerve growth factor receptor

International Nuclear Information System (INIS)

Hempstead, B.; Patil, N.; Olson, K.; Chao, M.

1988-01-01

An essential molecule in the translocation of information by nerve growth factor (NGF) to responsive cells is the cell-surface receptor for NGF. This paper presents information on the genomic structure of the NGF receptor gene, NGF receptor models, and transfection of NGF receptors. Equilibrium binding of [ 125 I]NGF to cells reveals two distinct affinity states for the NGF receptor. The human NGF receptor gene is a single-copy gene, consisting of six exons that span 23 kb. The receptor gene is capable of being transferred to fibroblast cells from human genomic DNA and expressed at high levels. The constitutive nature of the receptor promoter sequence is a partial explanation of why this tissue-specific gene is expressed efficiently in a variety of nonneuronal cells after genomic gene transfer. The two kinetic forms of the NGF receptor appear to be encoded by the same protein, which is the product of a single gene

Forster Resonance Energy Transfer (FRET) Analysis of Dual CFP/YFP Labeled AMPA Receptors Reveals Structural Rearrangement within the C-Terminal Domain during Receptor Activation

DEFF Research Database (Denmark)

Zachariassen, Linda Grønborg; Katchan, Mila; Plested, Andrew

2014-01-01

that retain function and display intrareceptor FRET. This includes a construct (GluA2-6Y-10C) containing YFP in the intracellular loop between the M1 and M2 membrane-embedded segments and CFP inserted in the C-ter- minal domain (CTD). GluA2-6Y-10C displays FRET with an efficiency of 0.11 while retaining wild......-type receptor expression and kinetic properties. We have used GluA2-6Y-10C to study conformational changes in homomeric GluA2 receptors during receptor activation. Our results show that the FRET efficiency is dependent on functional state of GluA2-6Y-10C and hereby indi- cates that the intracellular CTD...

WATER DEFICIT ENSURES THE PHOTOCHEMICAL EFFICIENCY OF Copaifera langsdorffii Desf1

Directory of Open Access Journals (Sweden)

Angélica Lino Rodrigues

2017-02-01

Full Text Available ABSTRACT The intensity and frequency of drought periods has increased according to climate change predictions. The fast overcome and recovery are important adaptive features for plant species found in regions presenting water shortage periods. Copaifera langsdorffii is a neotropical species that has developed leaves presenting physiological mechanisms and morphological adaptations that allow its survival under seasonal water stress. We aimed in this work to observe substantial physiological responses for water saving and damage representative to the photochemical reaction after exposed plants to water stress and to subsequent recovery. We found in plants mechanisms to control water loss through the lower stomatal conductance, even after rehydration. It goes against the rapid recovery of leaves, indicated by the relative water content values restored to previously unstressed plants. Stomatal conductance was the only variable presenting high plasticity index. In photochemical activity, the species presented higher photochemical quenching, electron transport rate and effective quantum yield of photosystem II when they were subjected to rehydration after water stress period. Our results suggest that C. langsdorffii presented rapid rehydration and higher photochemical efficiency even after water restriction. These data demonstrate that this species can be used as a model for physiological studies due to the adjustment developed in response to different environmental schemes.

Gene Transfer and Molecular Cloning of the Human NGF Receptor

Science.gov (United States)

Chao, Moses V.; Bothwell, Mark A.; Ross, Alonzo H.; Koprowski, Hilary; Lanahan, Anthony A.; Buck, C. Randall; Sehgal, Amita

1986-04-01

Nerve growth factor (NGF) and its receptor are important in the development of cells derived from the neural crest. Mouse L cell transformants have been generated that stably express the human NGF receptor gene transfer with total human DNA. Affinity cross-linking, metabolic labeling and immunoprecipitation, and equilibrium binding with 125I-labeled NGF revealed that this NGF receptor had the same size and binding characteristics as the receptor from human melanoma cells and rat PC12 cells. The sequences encoding the NGF receptor were molecularly cloned using the human Alu repetitive sequence as a probe. A cosmid clone that contained the human NGF receptor gene allowed efficient transfection and expression of the receptor.

ESSENCE OF THE PROBLEM OF ENSURING FOOD SECURITY

OpenAIRE

Lalayan G. G.

2013-01-01

In this article we have revealed the essence of the problem of ensuring food security in detail. The components of economic safety at macroeconomic level are described, defining conditions of ensuring national food security are shown

Cetuximab in combination with anti-human IgG antibodies efficiently down-regulates the EGF receptor by macropinocytosis

Energy Technology Data Exchange (ETDEWEB)

Berger, Christian [Department of Pathology, Oslo University Hospital, Rikshospitalet, Post box 4950 Nydalen, 0424 Oslo (Norway); Madshus, Inger Helene [Institute of Pathology, University of Oslo, Rikshospitalet, 0027 Oslo (Norway); Department of Pathology, Oslo University Hospital, Rikshospitalet, Post box 4950 Nydalen, 0424 Oslo (Norway); Stang, Espen, E-mail: espsta@rr-research.no [Department of Pathology, Oslo University Hospital, Rikshospitalet, Post box 4950 Nydalen, 0424 Oslo (Norway)

2012-12-10

The monoclonal antibody C225 (Cetuximab) blocks binding of ligand to the epidermal growth factor receptor (EGFR). In addition, it is known that incubation with C225 induces endocytosis of the EGFR. This endocytosis has previously been shown to be increased when C225 is combined with an additional monoclonal anti-EGFR antibody. However, the effects of antibody combinations on EGFR activation, endocytosis, trafficking and degradation have been unclear. By binding a secondary antibody to the C225-EGFR complex, we here demonstrate that a combination of antibodies can efficiently internalize and degrade the EGFR. Although the combination of antibodies activated the EGFR kinase and induced ubiquitination of the EGFR, the kinase activity was not required for internalization of the EGFR. In contrast to EGF-induced EGFR down-regulation, the antibody combination efficiently degraded the EGFR without initiating downstream proliferative signaling. The antibody-induced internalization of EGFR was found not to depend on clathrin and/or dynamin, but depended on actin polymerization, suggesting induction of macropinocytosis. Macropinocytosis may cause internalization of large membrane areas, and this could explain the highly efficient internalization of the EGFR induced by combination of antibodies. -- Highlight: Black-Right-Pointing-Pointer Cetuximab induced endocytosis of EGFR increases upon combination with anti-human IgG. Black-Right-Pointing-Pointer Antibody combination causes internalization of EGFR by macropinocytosis. Black-Right-Pointing-Pointer Antibody-induced internalization of EGFR is independent of EGFR kinase activity. Black-Right-Pointing-Pointer Antibody combination may have a zipper effect and cross-link EGFRs on neighboring cells.

Ensuring effective project management

International Nuclear Information System (INIS)

Ward, J.N.

1980-01-01

A brief description is given of the organisation methods employed by the Bechtel Power Corporation, in their contract with Mississippi Power and Light Company for the design, construction and procurement activities for the Grand Gulf Nuclear Station. The aim is to ensure effective management, and good communications at all stages of construction, between the project team and the client. (U.K.)

Ensuring Software IP Cleanliness

OpenAIRE

Mahshad Koohgoli; Richard Mayer

2007-01-01

At many points in the life of a software enterprise, determination of intellectual property (IP) cleanliness becomes critical. The value of an enterprise that develops and sells software may depend on how clean the software is from the IP perspective. This article examines various methods of ensuring software IP cleanliness and discusses some of the benefits and shortcomings of current solutions.

Interleukin 18 secretion and its effect in improving Chimeric Antigen Receptors efficiency

Science.gov (United States)

Kim, Jae-Kun

Clinical trials have shown that chimeric antigen receptor T cells modified to target cancer cells expressing a surface antigen found on immature B-cells. The purpose of this experiment is to take a pro-inflammatory cytokine, and analyze its effect in improving the efficiency of the T cells. IL-18 has been previously shown to recruit T cells to the tumor site and improve their secretion of cytotoxic cytokines. A human model of the proposed armored T cell has been created and has shown success in combating cancer cells in vitro. The next step is to design and produce a murine model to test in vivo in immunocompetent mice. This research project aimed to create two models: one utilizing 2A peptides and another utilizing IRES elements as a multicistronic vector. Both models would require the insertion of the desired genes into SFG backbones. IRES, a DNA element which acts as a binding site for the transcriptional machinery to recognize which part of the DNA to transcribe, commonly found in bicistronic vectors, is large with 500-600 base pairs, and has a lower transgene expression rate. P2A is smaller, only consisting of about 20 amino acids, and typically has a higher transgene expression rate, which may or may not result in higher effectiveness of the model. I would like to thank Dr. Renier Brentjens for being a mentor who cared about giving his interns as much educational value as possible.

Highly efficient gene transfer using a retroviral vector into murine T cells for preclinical chimeric antigen receptor-expressing T cell therapy

International Nuclear Information System (INIS)

Kusabuka, Hotaka; Fujiwara, Kento; Tokunaga, Yusuke; Hirobe, Sachiko; Nakagawa, Shinsaku; Okada, Naoki

2016-01-01

Adoptive immunotherapy using chimeric antigen receptor-expressing T (CAR-T) cells has attracted attention as an efficacious strategy for cancer treatment. To prove the efficacy and safety of CAR-T cell therapy, the elucidation of immunological mechanisms underlying it in mice is required. Although a retroviral vector (Rv) is mainly used for the introduction of CAR to murine T cells, gene transduction efficiency is generally less than 50%. The low transduction efficiency causes poor precision in the functional analysis of CAR-T cells. We attempted to improve the Rv gene transduction protocol to more efficiently generate functional CAR-T cells by optimizing the period of pre-cultivation and antibody stimulation. In the improved protocol, gene transduction efficiency to murine T cells was more than 90%. In addition, almost all of the prepared murine T cells expressed CAR after puromycin selection. These CAR-T cells had antigen-specific cytotoxic activity and secreted multiple cytokines by antigen stimulation. We believe that our optimized gene transduction protocol for murine T cells contributes to the advancement of T cell biology and development of immunotherapy using genetically engineered T cells. - Highlights: • We established highly efficient gene transduction protocols for murine T cells. • CD8"+ CAR-T cells had antigen-specific cytotoxic activity. • CD4"+ CAR-T cells secreted multiple cytokines by antigen stimulation. • This finding can contribute to the development of T-cell biology and immunotherapy.

Highly efficient gene transfer using a retroviral vector into murine T cells for preclinical chimeric antigen receptor-expressing T cell therapy

Energy Technology Data Exchange (ETDEWEB)

Kusabuka, Hotaka; Fujiwara, Kento; Tokunaga, Yusuke; Hirobe, Sachiko; Nakagawa, Shinsaku, E-mail: nakagawa@phs.osaka-u.ac.jp; Okada, Naoki, E-mail: okada@phs.osaka-u.ac.jp

2016-04-22

Adoptive immunotherapy using chimeric antigen receptor-expressing T (CAR-T) cells has attracted attention as an efficacious strategy for cancer treatment. To prove the efficacy and safety of CAR-T cell therapy, the elucidation of immunological mechanisms underlying it in mice is required. Although a retroviral vector (Rv) is mainly used for the introduction of CAR to murine T cells, gene transduction efficiency is generally less than 50%. The low transduction efficiency causes poor precision in the functional analysis of CAR-T cells. We attempted to improve the Rv gene transduction protocol to more efficiently generate functional CAR-T cells by optimizing the period of pre-cultivation and antibody stimulation. In the improved protocol, gene transduction efficiency to murine T cells was more than 90%. In addition, almost all of the prepared murine T cells expressed CAR after puromycin selection. These CAR-T cells had antigen-specific cytotoxic activity and secreted multiple cytokines by antigen stimulation. We believe that our optimized gene transduction protocol for murine T cells contributes to the advancement of T cell biology and development of immunotherapy using genetically engineered T cells. - Highlights: • We established highly efficient gene transduction protocols for murine T cells. • CD8{sup +} CAR-T cells had antigen-specific cytotoxic activity. • CD4{sup +} CAR-T cells secreted multiple cytokines by antigen stimulation. • This finding can contribute to the development of T-cell biology and immunotherapy.

Ensuring services to the poor : learning from LLPMS

International Development Research Centre (IDRC) Digital Library (Canada)

fajardojp

necessary steps to delivery services to ensure providing basic facilities but poverty remains central ... services, technological transfer, imparting training, input supply within reasonable ... Providing education, ensuring health facility, safe ..... a workshop organised to get feedback on the methodology of LLPMS the officials of.

Ensuring Software IP Cleanliness

Directory of Open Access Journals (Sweden)

Mahshad Koohgoli

2007-12-01

Full Text Available At many points in the life of a software enterprise, determination of intellectual property (IP cleanliness becomes critical. The value of an enterprise that develops and sells software may depend on how clean the software is from the IP perspective. This article examines various methods of ensuring software IP cleanliness and discusses some of the benefits and shortcomings of current solutions.

The GPRC6A Receptor displays Constitutive Internalization and Sorting to the Slow Recycling Pathway

DEFF Research Database (Denmark)

Jacobsen, Stine Engesgaard; Ammendrup-Johnsen, Ina; Jansen, Anna Mai

2017-01-01

The class C G protein-coupled receptor GPRC6A is a putative nutrient sensing receptor and represents a possible new drug target in metabolic disorders. However, the specific physiological role of this receptor has yet to be identified, and the mechanisms regulating its activity and cell surface...... availability also remain enigmatic. In the present study, we investigated the trafficking properties of GPRC6A by use of both a classical antibody feeding internalization assay in which cells were visualized using confocal microscopy and a novel internalization assay that is based on real-time measurements...... slow recycling pathway, which may be responsible for ensuring a persistent pool of GPRC6A receptors at the cell surface despite chronic agonist exposure. Distinct trafficking pathways have been reported for several of the class C receptors, and our results thus substantiate that non...

Structure of unliganded HSV gD reveals a mechanism for receptor-mediated activation of virus entry

Energy Technology Data Exchange (ETDEWEB)

Krummenacher, Claude; Supekar, Vinit M.; Whitbeck, J. Charles; Lazear, Eric; Connolly, Sarah A.; Eisenberg, Roselyn J.; Cohen, Gary H.; Wiley, Don C.; Carfi, Andrea (UPENN); (IRBM); (CHLMM)

2010-07-19

Herpes simplex virus (HSV) entry into cells requires binding of the envelope glycoprotein D (gD) to one of several cell surface receptors. The 50 C-terminal residues of the gD ectodomain are essential for virus entry, but not for receptor binding. We have determined the structure of an unliganded gD molecule that includes these C-terminal residues. The structure reveals that the C-terminus is anchored near the N-terminal region and masks receptor-binding sites. Locking the C-terminus in the position observed in the crystals by an intramolecular disulfide bond abolished receptor binding and virus entry, demonstrating that this region of gD moves upon receptor binding. Similarly, a point mutant that would destabilize the C-terminus structure was nonfunctional for entry, despite increased affinity for receptors. We propose that a controlled displacement of the gD C-terminus upon receptor binding is an essential feature of HSV entry, ensuring the timely activation of membrane fusion.

Low-Cost, High Efficiency, Silicon Based Photovoltaic Devices

Science.gov (United States)

2015-08-27

for photovoltaic applications. Figure 14: (a) Absorption and scattering efficiencies versus sizes of Au nanoparticle at 550 nm, (b) scattering...efficiency as a function of wavelength for different Au nanoparticles sizes . 32 Review of plasmonics light trapping for photovoltaic application...ensure that the irradiation variation was within 3%. The external quantum efficiency (EQE) system used a 300W Xenon light source with a spot size of 1mm

Ensuring safe water in post-chemical, biological, radiological and nuclear emergencies

Science.gov (United States)

Amar, Praveen Kumar

2010-01-01

Disaster scenarios are dismal and often result in mass displacement and migration of people. In eventuality of emergency situations, people need to be rehabilitated and provided with an adequate supply of drinking water, the most essential natural resource needed for survival, which is often not easily available even during non-disaster periods. In the aftermath of a natural or human-made disaster affecting mankind and livestock, the prime aim is to ensure supply of safe water to reduce the occurrence and spread of water borne disease due to interrupted, poor and polluted water supply. Chemical, biological, radiological and nuclear (CBRN) emergencies augment the dilemma as an additional risk of “contamination” is added. The associated risks posed to health and life should be reduced to as low as reasonably achievable. Maintaining a high level of preparedness is the crux of quick relief and efficient response to ensure continuous supply of safe water, enabling survival and sustenance. The underlying objective would be to educate and train the persons concerned to lay down the procedures for the detection, cleaning, and treatment, purification including desalination, disinfection, and decontamination of water. The basic information to influence the organization of preparedness and execution of relief measures at all levels while maintaining minimum standards in water management at the place of disaster, are discussed in this article. PMID:21829321

Ensuring safe water in post-chemical, biological, radiological and nuclear emergencies

Directory of Open Access Journals (Sweden)

Praveen Kumar Amar

2010-01-01

Full Text Available Disaster scenarios are dismal and often result in mass displacement and migration of people. In eventuality of emergency situations, people need to be rehabilitated and provided with an adequate supply of drinking water, the most essential natural resource needed for survival, which is often not easily available even during non-disaster periods. In the aftermath of a natural or human-made disaster affecting mankind and livestock, the prime aim is to ensure supply of safe water to reduce the occurrence and spread of water borne disease due to interrupted, poor and polluted water supply. Chemical, biological, radiological and nuclear (CBRN emergencies augment the dilemma as an additional risk of "contamination" is added. The associated risks posed to health and life should be reduced to as low as reasonably achievable. Maintaining a high level of preparedness is the crux of quick relief and efficient response to ensure continuous supply of safe water, enabling survival and sustenance. The underlying objective would be to educate and train the persons concerned to lay down the procedures for the detection, cleaning, and treatment, purification including desalination, disinfection, and decontamination of water. The basic information to influence the organization of preparedness and execution of relief measures at all levels while maintaining minimum standards in water management at the place of disaster, are discussed in this article.

Analysis of the Romanian Insurance Market Based on Ensuring and Exercising Consumers` Right to Claim

Directory of Open Access Journals (Sweden)

Dan Armeanu

2014-05-01

Full Text Available In the financial market of insurance, consumer protection represents an important component contributing to the stability, discipline and efficiency of the market. In this respect, the activity of educating and informing insurance consumers on ensuring and exercising their right to claim plays a leading role in the mechanism of consumer protection. This study aims to improve the decision-making capacity of the financial services consumers from the Romanian insurance market through better information on ensuring and exercising their right to claim under the legislation. Thus, by applying three data analysis techniques – principal components analysis, cluster analysis and discriminant analysis – to the data regarding the petitions that were registered by the 41 insurance companies which operated in the Romanian market in 2012, a classification that assesses the insurance market transparency is achieved, resulting in a better information for consumers and, hence, the improvement of their protection through reducing the level of transactions that are harmful to consumers

Building a Model for Optimization of Informational-Analytical Ensuring of Cost Management of Industrial Enterprise

Directory of Open Access Journals (Sweden)

Lisovskyi Ihor V

2015-09-01

Full Text Available The article examines peculiarities of building a model of informational-analytical optimization of cost management. The main sources of information together with approaches to cost management of industrial enterprises have been identified. In order to ensure the successful operation of enterprise in the conditions of growing manifestations of crisis, a continuous improving of the system for enterprise management along with the most important elements, which are necessary for its normal functioning, should be carried out. One of these so important elements are costs of enterprise. Accordingly, for an effective cost management, the most appropriate management approaches and tools must be used, based on a proper informational-analytical support of all processes. The article proposes an optimization model of informationalanalytical ensuring of cost management of industrial enterprises, which will serve as a ground for more informed and economically feasible solutions. A combination of best practices and tools to improve the efficiency of enterprise management has been proposed

Efficiency of supply chain management. Strategic and operational approach

Directory of Open Access Journals (Sweden)

Grzegorz Lichocik

2013-06-01

Full Text Available Background: One of the most important issues subject to theoretical considerations and empirical studies is the measurement of efficiency of activities in logistics and supply chain management. Simultaneously, efficiency is one of the terms interpreted in an ambiguous and multi-aspect manner, depending on the subject of a study. The multitude of analytical dimensions of this term results in the fact that, apart from economic efficiency being the basic study area, other dimensions perceived as an added value by different groups of supply chain participants become more and more important. Methods: The objective of this paper is to attempt to explain the problem of supply chain management efficiency in the context of general theoretical considerations relating to supply chain management. The authors have also highlighted determinants and practical implications of supply chain management efficiency in strategic and operational contexts. The study employs critical analyses of logistics literature and the free-form interview with top management representatives of a company operating in the TSL sector. Results: We must find a comprehensive approach to supply chain efficiency including all analytical dimensions connected with real goods and services flow. An effective supply chain must be cost-effective (ensuring economic efficiency of a chain, functional (reducing processes, lean, minimising the number of links in the chain to the necessary ones, adapting supply chain participants' internal processes to a common objective based on its efficiency and ensuring high quality of services (customer-oriented logistics systems. Conclusions: Efficiency of supply chains is not only a task for which a logistics department is responsible as it is a strategic decision taken by the management as regards the method of future company's operation. Correctly planned and fulfilled logistics tasks may result in improving performance of a company as well as the whole

The Prerequisites for Implementing and Ensuring the Efficiency of Marketing Audit at the Publishing and Printing Enterprises

Directory of Open Access Journals (Sweden)

Bezpalko Iryna R.

2017-03-01

Full Text Available The article is aimed at defining the prerequisites for necessity of successful and efficient implementation of the practice of marketing audit at the domestic publishing and printing enterprises. It has been determined that in the highly competitive market of the publishing and printing services, as well as systemic problems of the domestic market, marketing audit can be an efficient tool for analysis and control on the definition of problems in the system for management of marketing activities of the publishing and printing enterprise, preventive identifying non-conformity of their status with requirements of the market environment, as well as developing recommendations on how to reduce such non-conformity. Determining and accounting external and internal factors that cause impact on quality and efficiency of marketing audit of entities in the publishing and printing market is the basis for development of the organizational-economic mechanism for implementation of such audit and possibilities for its active implementation in the domestic market conditions.

Seven transmembrane G protein-coupled receptor repertoire of gastric ghrelin cells

DEFF Research Database (Denmark)

Engelstoft, Maja S; Park, Won-Mee; Sakata, Ichiro

2013-01-01

The molecular mechanisms regulating secretion of the orexigenic-glucoregulatory hormone ghrelin remain unclear. Based on qPCR analysis of FACS-purified gastric ghrelin cells, highly expressed and enriched 7TM receptors were comprehensively identified and functionally characterized using in vitro......, ex vivo and in vivo methods. Five Gαs-coupled receptors efficiently stimulated ghrelin secretion: as expected the β1-adrenergic, the GIP and the secretin receptors but surprisingly also the composite receptor for the sensory neuropeptide CGRP and the melanocortin 4 receptor. A number of Gαi....../o-coupled receptors inhibited ghrelin secretion including somatostatin receptors SSTR1, SSTR2 and SSTR3 and unexpectedly the highly enriched lactate receptor, GPR81. Three other metabolite receptors known to be both Gαi/o- and Gαq/11-coupled all inhibited ghrelin secretion through a pertussis toxin-sensitive Gαi...

Edge-Based Efficient Search over Encrypted Data Mobile Cloud Storage.

Science.gov (United States)

Guo, Yeting; Liu, Fang; Cai, Zhiping; Xiao, Nong; Zhao, Ziming

2018-04-13

Smart sensor-equipped mobile devices sense, collect, and process data generated by the edge network to achieve intelligent control, but such mobile devices usually have limited storage and computing resources. Mobile cloud storage provides a promising solution owing to its rich storage resources, great accessibility, and low cost. But it also brings a risk of information leakage. The encryption of sensitive data is the basic step to resist the risk. However, deploying a high complexity encryption and decryption algorithm on mobile devices will greatly increase the burden of terminal operation and the difficulty to implement the necessary privacy protection algorithm. In this paper, we propose ENSURE (EfficieNt and SecURE), an efficient and secure encrypted search architecture over mobile cloud storage. ENSURE is inspired by edge computing. It allows mobile devices to offload the computation intensive task onto the edge server to achieve a high efficiency. Besides, to protect data security, it reduces the information acquisition of untrusted cloud by hiding the relevance between query keyword and search results from the cloud. Experiments on a real data set show that ENSURE reduces the computation time by 15% to 49% and saves the energy consumption by 38% to 69% per query.

Edge-Based Efficient Search over Encrypted Data Mobile Cloud Storage

Directory of Open Access Journals (Sweden)

Yeting Guo

2018-04-01

Full Text Available Smart sensor-equipped mobile devices sense, collect, and process data generated by the edge network to achieve intelligent control, but such mobile devices usually have limited storage and computing resources. Mobile cloud storage provides a promising solution owing to its rich storage resources, great accessibility, and low cost. But it also brings a risk of information leakage. The encryption of sensitive data is the basic step to resist the risk. However, deploying a high complexity encryption and decryption algorithm on mobile devices will greatly increase the burden of terminal operation and the difficulty to implement the necessary privacy protection algorithm. In this paper, we propose ENSURE (EfficieNt and SecURE, an efficient and secure encrypted search architecture over mobile cloud storage. ENSURE is inspired by edge computing. It allows mobile devices to offload the computation intensive task onto the edge server to achieve a high efficiency. Besides, to protect data security, it reduces the information acquisition of untrusted cloud by hiding the relevance between query keyword and search results from the cloud. Experiments on a real data set show that ENSURE reduces the computation time by 15% to 49% and saves the energy consumption by 38% to 69% per query.

Edge-Based Efficient Search over Encrypted Data Mobile Cloud Storage

Science.gov (United States)

Liu, Fang; Cai, Zhiping; Xiao, Nong; Zhao, Ziming

2018-01-01

Smart sensor-equipped mobile devices sense, collect, and process data generated by the edge network to achieve intelligent control, but such mobile devices usually have limited storage and computing resources. Mobile cloud storage provides a promising solution owing to its rich storage resources, great accessibility, and low cost. But it also brings a risk of information leakage. The encryption of sensitive data is the basic step to resist the risk. However, deploying a high complexity encryption and decryption algorithm on mobile devices will greatly increase the burden of terminal operation and the difficulty to implement the necessary privacy protection algorithm. In this paper, we propose ENSURE (EfficieNt and SecURE), an efficient and secure encrypted search architecture over mobile cloud storage. ENSURE is inspired by edge computing. It allows mobile devices to offload the computation intensive task onto the edge server to achieve a high efficiency. Besides, to protect data security, it reduces the information acquisition of untrusted cloud by hiding the relevance between query keyword and search results from the cloud. Experiments on a real data set show that ENSURE reduces the computation time by 15% to 49% and saves the energy consumption by 38% to 69% per query. PMID:29652810

Duality ensures modular covariance

International Nuclear Information System (INIS)

Li Miao; Yu Ming

1989-11-01

We show that the modular transformations for one point functions on the torus, S(n), satisfy the polynomial equations derived by Moore and Seiberg, provided the duality property of the model is ensured. The formula for S(n) is derived by us previously and should be valid for any conformal field theory. As a consequence, the full consistency conditions for modular invariance at higher genus are completely guaranteed by duality of the theory on the sphere. (orig.)

Rapid and efficient radiosynthesis of [123I]I-PK11195, a single photon emission computed tomography tracer for peripheral benzodiazepine receptors

International Nuclear Information System (INIS)

Pimlott, Sally L.; Stevenson, Louise; Wyper, David J.; Sutherland, Andrew

2008-01-01

Introduction: [ 123 I]I-PK11195 is a high-affinity single photon emission computed tomography radiotracer for peripheral benzodiazepine receptors that has previously been used to measure activated microglia and to assess neuroinflammation in the living human brain. This study investigates the radiosynthesis of [ 123 I]I-PK11195 in order to develop a rapid and efficient method that obtains [ 123 I]I-PK11195 with a high specific activity for in vivo animal and human imaging studies. Methods: The synthesis of [ 123 I]I-PK11195 was evaluated using a solid-state interhalogen exchange method and an electrophilic iododestannylation method, where bromine and trimethylstannyl derivatives were used as precursors, respectively. In the electrophilic iododestannylation method, the oxidants peracetic acid and chloramine-T were both investigated. Results: Electrophilic iododestannylation produced [ 123 I]I-PK11195 with a higher isolated radiochemical yield and a higher specific activity than achievable using the halogen exchange method investigated. Using chloramine-T as oxidant provided a rapid and efficient method of choice for the synthesis of [ 123 I]I-PK11195. Conclusions: [ 123 I]I-PK11195 has been successfully synthesized via a rapid and efficient electrophilic iododestannylation method, producing [ 123 I]I-PK11195 with a higher isolated radiochemical yield and a higher specific activity than previously achieved

Putative chemosensory receptors of the codling moth, Cydia pomonella, identified by antennal transcriptome analysis.

Directory of Open Access Journals (Sweden)

Jonas M Bengtsson

Full Text Available The codling moth, Cydia pomonella, is an important fruit pest worldwide. As nocturnal animals, adults depend to a large extent on olfactory cues for detection of food and mates, and, for females, oviposition sites. In insects, odor detection is mediated by odorant receptors (ORs and ionotropic receptors (IRs, which ensure the specificity of the olfactory sensory neuron responses. In this study, our aim was to identify chemosensory receptors in the codling moth as a means to uncover new targets for behavioral interference. Using next-generation sequencing techniques, we identified a total of 43 candidate ORs, one gustatory receptor and 15 IRs in the antennal transcriptome. Through Blast and sequence similarity analyses we annotated the insect obligatory co-receptor ORco, five genes clustering in a conserved clade containing sex pheromone receptors, one homolog of the Bombyx mori female-enriched receptor BmorOR30 (but no homologs of the other B. mori female-enriched receptors and one gene clustering in the sugar receptor family. Among the candidate IRs, we identified homologs of the two highly conserved co-receptors IR8a and IR25a, and one homolog of an IR involved in phenylethyl amine detection in Drosophila. Our results open for functional characterization of the chemosensory receptors of C. pomonella, with potential for new or refined applications of semiochemicals for control of this pest insect.

Two-step membrane binding by the bacterial SRP receptor enable efficient and accurate Co-translational protein targeting.

Science.gov (United States)

Hwang Fu, Yu-Hsien; Huang, William Y C; Shen, Kuang; Groves, Jay T; Miller, Thomas; Shan, Shu-Ou

2017-07-28

The signal recognition particle (SRP) delivers ~30% of the proteome to the eukaryotic endoplasmic reticulum, or the bacterial plasma membrane. The precise mechanism by which the bacterial SRP receptor, FtsY, interacts with and is regulated at the target membrane remain unclear. Here, quantitative analysis of FtsY-lipid interactions at single-molecule resolution revealed a two-step mechanism in which FtsY initially contacts membrane via a Dynamic mode, followed by an SRP-induced conformational transition to a Stable mode that activates FtsY for downstream steps. Importantly, mutational analyses revealed extensive auto-inhibitory mechanisms that prevent free FtsY from engaging membrane in the Stable mode; an engineered FtsY pre-organized into the Stable mode led to indiscriminate targeting in vitro and disrupted FtsY function in vivo. Our results show that the two-step lipid-binding mechanism uncouples the membrane association of FtsY from its conformational activation, thus optimizing the balance between the efficiency and fidelity of co-translational protein targeting.

Genome-wide Specificity of Highly Efficient TALENs and CRISPR/Cas9 for T Cell Receptor Modification

Directory of Open Access Journals (Sweden)

Friederike Knipping

2017-03-01

Full Text Available In T cells with transgenic high-avidity T cell receptors (TCRs, endogenous and transferred TCR chains compete for surface expression and may pair inappropriately, potentially causing autoimmunity. To knock out endogenous TCR expression, we assembled 12 transcription activator-like effector nucleases (TALENs and five guide RNAs (gRNAs from the clustered regularly interspaced short palindromic repeats (CRISPR/CRISPR-associated (Cas9 system. Using TALEN mRNA, TCR knockout was successful in up to 81% of T cells. Additionally, we were able to verify targeted gene addition of a GFP gene by homology-directed repair at the TALEN target site, using a donor suitable for replacement of the reporter transgene with therapeutic TCR chains. Remarkably, analysis of TALEN and CRISPR/Cas9 specificity using integrase-defective lentiviral vector capture revealed only one off-target site for one of the gRNAs and three off-target sites for both of the TALENs, indicating a high level of specificity. Collectively, our work shows highly efficient and specific nucleases for T cell engineering.

The Measurement and Determinants of Economic Efficiency of ...

African Journals Online (AJOL)

The Measurement and Determinants of Economic Efficiency of Microfinance Institutions ... players in socio-economic development especially in developing countries. ... savings products to improve on portfolio quality and ensure sustainability; ...

Perspectives of Security Ensuring within the Framework of Barcelona Process

Directory of Open Access Journals (Sweden)

T N Kirabaev

2009-06-01

Full Text Available Barcelona process was aimed to become an important mechanism in the realization of ideas of peace, stability and security ensuring in the Mediterranean Sea region. Cooperation in the sphere of security ensuring means openness of the regional states, social and economic reforms, human rights protection. The article deals with the problem of security ensuring by nonmilitary means.

Measurement and evaluation of energy efficiency programs: California and South Korea

International Nuclear Information System (INIS)

Vine, E.; Rhee, C.H.; Lee, K.D.

2006-01-01

One of the key challenges for countries facing electric utility restructuring is to ensure that key public goods, such as energy efficiency programs, do not lose support but are maintained and enhanced via regulatory policy and government action. Moreover, an infrastructure and process also needs to be designed and implemented for conducting the measurement and evaluation of energy efficiency programs. This paper describes the experiences of California and the Republic of Korea (Korea) in addressing these issues. These case studies confirm that the active involvement of regulatory bodies is needed to ensure that energy efficiency investments continue. The case studies also show that the development of an infrastructure and process for conducting rigorous measurement and evaluation takes time and needs the active participation of many stakeholders

Ensuring microbiological safety of commercial eggs by gamma irradiation

International Nuclear Information System (INIS)

Hammad, A.A; Swailam, H.M.; Abd El-Rahim, E.A.; Shallan, M.A; Aly, W.F.

2009-01-01

Egg shell sanitizing practices are necessary to improve microbiological safety of fresh eggs. In this work, fifteen fresh eggs samples of each (balady, white and brown eggs) were collected from different local supermarkets to evaluate their microbiological quality. The results indicated that balady eggs were higher in microbial population in comparison with the two other varieties. Salmonella spp. was detected in 9 (60%) samples of balady eggs. The effect of gamma irradiation at dose of 0,2,3 and 4 kGy on microbiological quality of balady eggs during storage at 4± 1 deg c for 35 days as well as on total cholesterol , ph, and total carotenoids contents were also investigated. The results showed that irradiation at 3 kGy reduced total aerobic bacterial counts. Whereas completely eliminated coliform bacteria, E.coli and salmonella spp. Total cholesterol and total carotenoids were decreased in yolk egg. irradiation dose of 3 kGy were efficient and sufficient for ensuring safety, maintain quality and extend shelf-life of balady eggs

Efficient production of membrane-integrated and detergent-soluble G protein-coupled receptors in Escherichia coli.

Science.gov (United States)

Link, A James; Skretas, Georgios; Strauch, Eva-Maria; Chari, Nandini S; Georgiou, George

2008-10-01

G protein-coupled receptors (GPCRs) are notoriously difficult to express, particularly in microbial systems. Using GPCR fusions with the green fluorescent protein (GFP), we conducted studies to identify bacterial host effector genes that result in a general and significant enhancement in the amount of membrane-integrated human GPCRs that can be produced in Escherichia coli. We show that coexpression of the membrane-bound AAA+ protease FtsH greatly enhances the expression yield of four different class I GPCRs, irrespective of the presence of GFP. Using this new expression system, we produced 0.5 and 2 mg/L of detergent-solubilized and purified full-length central cannabinoid receptor (CB1) and bradykinin receptor 2 (BR2) in shake flask cultures, respectively, two proteins that had previously eluded expression in microbial systems.

Europa Passage, Hamburg. Pumps ensure thermal comfort at all levels; Die Europa Passage in Hamburg. Pumpen sorgen fuer Komfort auf allen Ebenen

Energy Technology Data Exchange (ETDEWEB)

Teders, Klaus

2009-07-01

The Europa Passage at Hamburg is a new shopping mall located directly on the Binnenalster river. It was constructed in 2006 and has 30,000 m{sup 2} of shop floor on five levels, which makes it one of Germany's biggest shopping malls. It is frequented every day by up to 40,000 visitors and more than 50,000 visitors on saturdays. In order to ensure optimum comfort even in peak times, the passage is equipped with state-of-the-art technical facilities. Energy-efficient pumps ensure reliable supply of all technical facilities. (orig.)

GPCRdb: an information system for G protein-coupled receptors.

Science.gov (United States)

Isberg, Vignir; Mordalski, Stefan; Munk, Christian; Rataj, Krzysztof; Harpsøe, Kasper; Hauser, Alexander S; Vroling, Bas; Bojarski, Andrzej J; Vriend, Gert; Gloriam, David E

2016-01-04

Recent developments in G protein-coupled receptor (GPCR) structural biology and pharmacology have greatly enhanced our knowledge of receptor structure-function relations, and have helped improve the scientific foundation for drug design studies. The GPCR database, GPCRdb, serves a dual role in disseminating and enabling new scientific developments by providing reference data, analysis tools and interactive diagrams. This paper highlights new features in the fifth major GPCRdb release: (i) GPCR crystal structure browsing, superposition and display of ligand interactions; (ii) direct deposition by users of point mutations and their effects on ligand binding; (iii) refined snake and helix box residue diagram looks; and (iii) phylogenetic trees with receptor classification colour schemes. Under the hood, the entire GPCRdb front- and back-ends have been re-coded within one infrastructure, ensuring a smooth browsing experience and development. GPCRdb is available at http://www.gpcrdb.org/ and it's open source code at https://bitbucket.org/gpcr/protwis. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Chronic suppression of μ-opioid receptor signaling in the nucleus accumbens attenuates development of diet-induced obesity in rats.

Science.gov (United States)

Lenard, N R; Zheng, H; Berthoud, H-R

2010-06-01

To test the hypothesis that micro-opioid receptor signaling in the nucleus accumbens contributes to hedonic (over)eating and obesity. To investigate the effects of chronic micro-opioid antagonism in the nucleus accumbens core or shell on intake of a palatable diet, and the development of diet-induced obesity in rats. Chronic blockade of micro-opioid receptor signaling in the nucleus accumbens core or shell was achieved by means of repeated injections (every 4-5 days) of the irreversible receptor antagonist beta-funaltrexamine (BFNA) over 3-5 weeks. The diet consisted of either a choice of high-fat chow, chocolate-flavored Ensure and regular chow (each nutritionally complete) or regular chow only. Intake of each food item, body weight and body fat mass were monitored throughout the study. The BFNA injections aimed at either the core or shell of the nucleus accumbens resulted in significantly attenuated intake of palatable diet, body weight gain and fat accretion, compared with vehicle control injections. The injection of BFNA in the core did not significantly change these parameters in chow-fed control rats. The injection of BFNA in the core and shell differentially affected intake of the two palatable food items: in the core, BFNA significantly reduced the intake of high-fat, but not of Ensure, whereas in the shell, it significantly reduced the intake of Ensure, but not of high-fat, compared with vehicle treatment. Endogenous micro-opioid receptor signaling in the nucleus accumbens core and shell is necessary for palatable diet-induced hyperphagia and obesity to fully develop in rats. Sweet and non-sweet fatty foods may be differentially processed in subcomponents of the ventral striatum.

DAF-12 Regulates a Connected Network of Genes to Ensure Robust Developmental Decisions

Science.gov (United States)

Stuckenholz, Carsten; Labhart, Paul; Alexiadis, Vassili; Martin, René; Knölker, Hans-Joachim; Fisher, Alfred L.

2011-01-01

The nuclear receptor DAF-12 has roles in normal development, the decision to pursue dauer development in unfavorable conditions, and the modulation of adult aging. Despite the biologic importance of DAF-12, target genes for this receptor are largely unknown. To identify DAF-12 targets, we performed chromatin immunoprecipitation followed by hybridization to whole-genome tiling arrays. We identified 1,175 genomic regions to be bound in vivo by DAF-12, and these regions are enriched in known DAF-12 binding motifs and act as DAF-12 response elements in transfected cells and in transgenic worms. The DAF-12 target genes near these binding sites include an extensive network of interconnected heterochronic and microRNA genes. We also identify the genes encoding components of the miRISC, which is required for the control of target genes by microRNA, as a target of DAF-12 regulation. During reproductive development, many of these target genes are misregulated in daf-12(0) mutants, but this only infrequently results in developmental phenotypes. In contrast, we and others have found that null daf-12 mutations enhance the phenotypes of many miRISC and heterochronic target genes. We also find that environmental fluctuations significantly strengthen the weak heterochronic phenotypes of null daf-12 alleles. During diapause, DAF-12 represses the expression of many heterochronic and miRISC target genes, and prior work has demonstrated that dauer formation can suppress the heterochronic phenotypes of many of these target genes in post-dauer development. Together these data are consistent with daf-12 acting to ensure developmental robustness by committing the animal to adult or dauer developmental programs despite variable internal or external conditions. PMID:21814518

Evidence for Heterodimerization and Functional Interaction of the Angiotensin Type 2 Receptor and the Receptor MAS.

Science.gov (United States)

Leonhardt, Julia; Villela, Daniel C; Teichmann, Anke; Münter, Lisa-Marie; Mayer, Magnus C; Mardahl, Maibritt; Kirsch, Sebastian; Namsolleck, Pawel; Lucht, Kristin; Benz, Verena; Alenina, Natalia; Daniell, Nicholas; Horiuchi, Masatsugu; Iwai, Masaru; Multhaup, Gerhard; Schülein, Ralf; Bader, Michael; Santos, Robson A; Unger, Thomas; Steckelings, Ulrike Muscha

2017-06-01

The angiotensin type 2 receptor (AT2R) and the receptor MAS are receptors of the protective arm of the renin-angiotensin system. They mediate strikingly similar actions. Moreover, in various studies, AT2R antagonists blocked the effects of MAS agonists and vice versa. Such cross-inhibition may indicate heterodimerization of these receptors. Therefore, this study investigated the molecular and functional interplay between MAS and the AT2R. Molecular interactions were assessed by fluorescence resonance energy transfer and by cross correlation spectroscopy in human embryonic kidney-293 cells transfected with vectors encoding fluorophore-tagged MAS or AT2R. Functional interaction of AT2R and MAS was studied in astrocytes with CX3C chemokine receptor-1 messenger RNA expression as readout. Coexpression of fluorophore-tagged AT2R and MAS resulted in a fluorescence resonance energy transfer efficiency of 10.8 ± 0.8%, indicating that AT2R and MAS are capable to form heterodimers. Heterodimerization was verified by competition experiments using untagged AT2R and MAS. Specificity of dimerization of AT2R and MAS was supported by lack of dimerization with the transient receptor potential cation channel, subfamily C-member 6. Dimerization of the AT2R was abolished when it was mutated at cysteine residue 35. AT2R and MAS stimulation with the respective agonists, Compound 21 or angiotensin-(1-7), significantly induced CX3C chemokine receptor-1 messenger RNA expression. Effects of each agonist were blocked by an AT2R antagonist (PD123319) and also by a MAS antagonist (A-779). Knockout of a single of these receptors made astrocytes unresponsive for both agonists. Our results suggest that MAS and the AT2R form heterodimers and that-at least in astrocytes-both receptors functionally depend on each other. © 2017 American Heart Association, Inc.

34 CFR 602.18 - Ensuring consistency in decision-making.

Science.gov (United States)

2010-07-01

... 34 Education 3 2010-07-01 2010-07-01 false Ensuring consistency in decision-making. 602.18 Section... relies on for making accrediting decisions is accurate; and (e) Provides the institution or program with... Criteria for Recognition Required Standards and Their Application § 602.18 Ensuring consistency in decision...

Genetic polymorphism of vitamin D receptor determines its metabolism and efficiency

OpenAIRE

O.A. Yakovleva; O.M. Nikolova; I.A. Doroshkevych; N.V. Shcherbeniuk

2017-01-01

The review represents the results of researches of vitamin D receptor characteristics and its genetic polymorphism, which is variable in different populations, and also depends on age and gender. This polymorphism determines the association of vitamin D different concentration with the probability of bronchial asthma or chronic obstructive pulmonary disease development, and therefore the different efficacy of drug correction of vitamin D deficiency. However, the scientific data are contradict...

Expressing exogenous functional odorant receptors in cultured olfactory sensory neurons

Directory of Open Access Journals (Sweden)

Fomina Alla F

2008-09-01

Full Text Available Abstract Background Olfactory discrimination depends on the large numbers of odorant receptor genes and differential ligand-receptor signaling among neurons expressing different receptors. In this study, we describe an in vitro system that enables the expression of exogenous odorant receptors in cultured olfactory sensory neurons. Olfactory sensory neurons in the culture express characteristic signaling molecules and, therefore, provide a system to study receptor function within its intrinsic cellular environment. Results We demonstrate that cultured olfactory sensory neurons express endogenous odorant receptors. Lentiviral vector-mediated gene transfer enables successful ectopic expression of odorant receptors. We show that the ectopically expressed mouse I7 is functional in the cultured olfactory sensory neurons. When two different odorant receptors are ectopically expressed simultaneously, both receptor proteins co-localized in the same olfactory sensory neurons up to 10 days in vitro. Conclusion This culture technique provided an efficient method to culture olfactory sensory neurons whose morphology, molecular characteristics and maturation progression resembled those observed in vivo. Using this system, regulation of odorant receptor expression and its ligand specificity can be studied in its intrinsic cellular environment.

Ligand-independent Thrombopoietin Mutant Receptor Requires Cell Surface Localization for Endogenous Activity*

OpenAIRE

Marty, Caroline; Chaligné, Ronan; Lacout, Catherine; Constantinescu, Stefan N.; Vainchenker, William; Villeval, Jean-Luc

2009-01-01

The activating W515L mutation in the thrombopoietin receptor (MPL) has been identified in primary myelofibrosis and essential thrombocythemia. MPL belongs to a subset of the cytokine receptor superfamily that requires the JAK2 kinase for signaling. We examined whether the ligand-independent MPLW515L mutant could signal intracellularly. Addition of the endoplasmic reticulum (ER) retention KDEL sequence to the receptor C terminus efficiently locked MPLW515L within its na...

Efficient semiconductor multicycle terahertz pulse source

Science.gov (United States)

Nugraha, P. S.; Krizsán, G.; Polónyi, Gy; Mechler, M. I.; Hebling, J.; Tóth, Gy; Fülöp, J. A.

2018-05-01

Multicycle THz pulse generation by optical rectification in GaP semiconductor nonlinear material is investigated by numerical simulations. It is shown that GaP can be an efficient and versatile source with up to about 8% conversion efficiency and a tuning range from 0.1 THz to about 7 THz. Contact-grating technology for pulse-front tilt can ensure an excellent focusability and scaling the THz pulse energy beyond 1 mJ. Shapeable infrared pump pulses with a constant intensity-modulation period can be delivered for example by a flexible and efficient dual-chirped optical parametric amplifier. Potential applications include linear and nonlinear THz spectroscopy and THz-driven acceleration of electrons.

The Role of TAM Family Receptors in Immune Cell Function: Implications for Cancer Therapy.

Science.gov (United States)

Paolino, Magdalena; Penninger, Josef M

2016-10-21

The TAM receptor protein tyrosine kinases-Tyro3, Axl, and Mer-are essential regulators of immune homeostasis. Guided by their cognate ligands Growth arrest-specific gene 6 (Gas6) and Protein S (Pros1), these receptors ensure the resolution of inflammation by dampening the activation of innate cells as well as by restoring tissue function through promotion of tissue repair and clearance of apoptotic cells. Their central role as negative immune regulators is highlighted by the fact that deregulation of TAM signaling has been linked to the pathogenesis of autoimmune, inflammatory, and infectious diseases. Importantly, TAM receptors have also been associated with cancer development and progression. In a cancer setting, TAM receptors have a dual regulatory role, controlling the initiation and progression of tumor development and, at the same time, the associated anti-tumor responses of diverse immune cells. Thus, modulation of TAM receptors has emerged as a potential novel strategy for cancer treatment. In this review, we discuss our current understanding of how TAM receptors control immunity, with a particular focus on the regulation of anti-tumor responses and its implications for cancer immunotherapy.

The Impact Of Occupational Hazards In Workplaces - Maintenance, A Main Target For Ensuring The Safety Of Working Equipment

Science.gov (United States)

Antonov, Anca Elena; Buica, Georgeta; Darabont, Doru Costin; Beiu, Constantin

2015-07-01

For use of work equipment having the economic performance and the highest level of safety, it must be ensured that it complies with the conditions set by the manufacturer in terms of putting into service, use and maintenance operations, ensuring appropriate technical and environmental requirements, including appropriate measures and means of protection. The research aimed to identify and analyze the occupational hazards associated to maintenance operations, in terms of the history of the adjustments, maintenance, cleaning and repair, including the case that occur after the incidents, capital repairs and upgrades. The results of the research consisted in the development of recommendations on the effective management of maintenance activities of work equipment and a software model to enable an efficient management of maintenance, as a tool for occupational hazards in companies - premise for increasing the competitiveness of employers in the market economy.

Efficient resource allocation scheme for visible-light communication system

Science.gov (United States)

Kim, Woo-Chan; Bae, Chi-Sung; Cho, Dong-Ho; Shin, Hong-Seok; Jung, D. K.; Oh, Y. J.

2009-01-01

A visible-light communication utilizing LED has many advantagies such as visibility of information, high SNR (Signal to Noise Ratio), low installation cost, usage of existing illuminators, and high security. Furthermore, exponentially increasing needs and quality of LED have helped the development of visible-light communication. The visibility is the most attractive property in visible-light communication system, but it is difficult to ensure visibility and transmission efficiency simultaneously during initial access because of the small amount of initial access process signals. In this paper, we propose an efficient resource allocation scheme at initial access for ensuring visibility with high resource utilization rate and low data transmission failure rate. The performance has been evaluated through the numerical analysis and simulation results.

Electrical energy efficiency technologies and applications

CERN Document Server

Sumper, Andreas

2012-01-01

The improvement of electrical energy efficiency is fast becoming one of the most essential areas of sustainability development, backed by political initiatives to control and reduce energy demand. Now a major topic in industry and the electrical engineering research community, engineers have started to focus on analysis, diagnosis and possible solutions. Owing to the complexity and cross-disciplinary nature of electrical energy efficiency issues, the optimal solution is often multi-faceted with a critical solutions evaluation component to ensure cost effectiveness. This single-source refer

25 CFR 39.409 - How does the OIEP Director ensure accountability?

Science.gov (United States)

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false How does the OIEP Director ensure accountability? 39.409... EQUALIZATION PROGRAM Accountability § 39.409 How does the OIEP Director ensure accountability? (a) The Director of OIEP must ensure accountability in student counts and student transportation by doing all of the...

Effect of Selective Prostaglandin E2 EP2 Receptor Agonist CP-533,536 on Voiding Efficiency in Rats with Midodrine-Induced Functional Urethral Obstruction.

Science.gov (United States)

Kurihara, Ryoko; Imazumi, Katsunori; Takamatsu, Hajime; Ishizu, Kenichiro; Yoshino, Taiji; Masuda, Noriyuki

2016-05-01

We investigated the effect of the selective prostaglandin E2 EP2 receptor agonist CP-533,536 on voiding efficiency in rats with midodrine-induced functional urethral obstruction. The effect of CP-533,536 (0.03-0.3 mg/kg, intravenous [i.v.]) on urethral perfusion pressure (UPP) was investigated in anesthetized rats pre-treated with midodrine (1 mg/kg, i.v.), which forms an active metabolite that acts as an α1 -adrenoceptor agonist. The effect of CP-533,536 (0.03-0.3 mg/kg, i.v.) on cystometric parameters was also investigated in anesthetized rats. In addition, the effect of CP-533,536 (0.03-0.3 mg/kg, i.v.) on residual urine volume (RV) and voiding efficiency (VE) was investigated in conscious rats treated with midodrine (1 mg/kg, i.v.). CP-533,536 dose-dependently decreased UPP elevated by midodrine in anesthetized rats. In contrast, CP-533,536 did not affect maximum voiding pressure, intercontraction interval, or intravesical threshold pressure. In conscious rats, midodrine (1 mg/kg, i.v.) markedly increased RV and reduced VE. CP-533,536 dose-dependently ameliorated increases in RV and decreases in VE induced by midodrine. These results suggest that a selective EP2 receptor agonist could ameliorate the elevation of RV and improve the reduction of VE in rats with functional urethral obstruction caused by stimulation of α1 -adrenoceptors. The mechanism of action might be not potentiation of bladder contraction but rather preferential relief of urethral constriction. © 2014 Wiley Publishing Asia Pty Ltd.

ITE, a novel endogenous nontoxic aryl hydrocarbon receptor ligand, efficiently suppresses EAU and T-cell-mediated immunity.

Science.gov (United States)

Nugent, Lindsey F; Shi, Guangpu; Vistica, Barbara P; Ogbeifun, Osato; Hinshaw, Samuel J H; Gery, Igal

2013-11-13

Ligands for aryl hydrocarbon receptor (AHR), such as dioxins, are highly toxic. One such ligand, TCDD, was found to exert potent immunosuppressive capacities in mice developing pathogenic autoimmune processes, including EAU, but its toxicity makes it unusable for humans. A recently identified endogenous AHR ligand, ITE, is also immunosuppressive, but is nontoxic and could therefore be useful for therapy in humans. Here, we tested ITE for its capacity to inhibit EAU and related immune responses. EAU was induced in B10.A mice by immunization with interphotoreceptor retinoid-binding protein (IRBP; 40 μg) in CFA. Treatment with ITE was by daily intraperitoneal injection of 0.2 mg. Disease severity was assessed by both fundoscopy and histological examination. Draining lymph node cells were tested for proliferation by thymidine uptake and for cytokine production and release by ELISA. In addition, the intracellular expression of cytokines and Foxp3 was determined by flow cytometry. Serum antibodies were measured by ELISA. Treatment with ITE efficiently inhibited the development of EAU in mice, as well as the cellular immune responses against IRBP and PPD. ITE treatment inhibited the expansion of both Th1 and Th17 subpopulations, as well as their release of the signature cytokines, IFN-gamma and IL-17. The treatment moderately increased, however, the proportion of Foxp3 expressing T-regulatory cells. Antibody production was not affected by the treatment. ITE, an endogenous AHR ligand, efficiently inhibits EAU development and related cellular immune responses. Being nontoxic, ITE may be considered for treatment of pathogenic immunity in humans.

ITE, A Novel Endogenous Nontoxic Aryl Hydrocarbon Receptor Ligand, Efficiently Suppresses EAU and T-Cell–Mediated Immunity

Science.gov (United States)

Nugent, Lindsey F.; Shi, Guangpu; Vistica, Barbara P.; Ogbeifun, Osato; Hinshaw, Samuel J. H.; Gery, Igal

2013-01-01

Purpose. Ligands for aryl hydrocarbon receptor (AHR), such as dioxins, are highly toxic. One such ligand, TCDD, was found to exert potent immunosuppressive capacities in mice developing pathogenic autoimmune processes, including EAU, but its toxicity makes it unusable for humans. A recently identified endogenous AHR ligand, ITE, is also immunosuppressive, but is nontoxic and could therefore be useful for therapy in humans. Here, we tested ITE for its capacity to inhibit EAU and related immune responses. Methods. EAU was induced in B10.A mice by immunization with interphotoreceptor retinoid-binding protein (IRBP; 40 μg) in CFA. Treatment with ITE was by daily intraperitoneal injection of 0.2 mg. Disease severity was assessed by both fundoscopy and histological examination. Draining lymph node cells were tested for proliferation by thymidine uptake and for cytokine production and release by ELISA. In addition, the intracellular expression of cytokines and Foxp3 was determined by flow cytometry. Serum antibodies were measured by ELISA. Results. Treatment with ITE efficiently inhibited the development of EAU in mice, as well as the cellular immune responses against IRBP and PPD. ITE treatment inhibited the expansion of both Th1 and Th17 subpopulations, as well as their release of the signature cytokines, IFN-gamma and IL-17. The treatment moderately increased, however, the proportion of Foxp3 expressing T-regulatory cells. Antibody production was not affected by the treatment. Conclusions. ITE, an endogenous AHR ligand, efficiently inhibits EAU development and related cellular immune responses. Being nontoxic, ITE may be considered for treatment of pathogenic immunity in humans. PMID:24150760

FEATURES TO ENSURE THE COMPETITIVENESS OF REINSURANCE OPERATIONS OF THE CEDENT AND THE REINSURER IN THE DOMESTIC AND INTERNATIONAL INSURANCE MARKET

Directory of Open Access Journals (Sweden)

V. Veretnov

2015-04-01

Full Text Available Cost-effectiveness of reinsurance operations significantly affect the competitiveness of the cedent and the reinsurer. At the same time, ensuring the competitiveness of reinsurance operations does not always lead to the economic efficiency of the cedent and the reinsurer. We give the definition of the concept of competitiveness of reinsurance operations. The features ensuring the competitiveness of reinsurance operations of the cedent and the reinsurer in the domestic and international insurance market. The use of these features allows you to not only improve the quality of reinsurance protection, which has a beneficial effect on the financial stability of the cedent, but provides such necessary, confidential professional and personal relationship of the cedent and the reinsurer.

Efficient silkworm expression of human GPCR (nociceptin receptor) by a Bombyx mori bacmid DNA system

International Nuclear Information System (INIS)

Kajikawa, Mizuho; Sasaki, Kaori; Wakimoto, Yoshitaro; Toyooka, Masaru; Motohashi, Tomoko; Shimojima, Tsukasa; Takeda, Shigeki; Park, Enoch Y.; Maenaka, Katsumi

2009-01-01

Guanine nucleotide-binding protein (G protein) coupled receptors (GPCRs) are frequently expressed by a baculovirus expression vector system (BEVS). We recently established a novel BEVS using the bacmid system of Bombyx mori nucleopolyhedrovirus (BmNPV), which is directly applicable for protein expression in silkworms. Here, we report the first example of GPCR expression in silkworms by the simple injection of BmNPV bacmid DNA. Human nociceptin receptor, an inhibitory GPCR, and its fusion protein with inhibitory G protein alpha subunit (G i α) were both successfully expressed in the fat bodies of silkworm larvae as well as in the BmNPV viral fraction. Its yield was much higher than that from Sf9 cells. The microsomal fractions including the nociceptin receptor fusion, which are easily prepared by only centrifugation steps, exhibited [ 35 S]GTPγS-binding activity upon specific stimulation by nociceptin. Therefore, this rapid method is easy-to-use and has a high expression level, and thus will be an important tool for human GPCR production.

Profiling neurotransmitter receptor expression in the Ambystoma mexicanum brain.

Science.gov (United States)

Reyes-Ruiz, Jorge Mauricio; Limon, Agenor; Korn, Matthew J; Nakamura, Paul A; Shirkey, Nicole J; Wong, Jamie K; Miledi, Ricardo

2013-03-22

Ability to regenerate limbs and central nervous system (CNS) is unique to few vertebrates, most notably the axolotl (Ambystoma sp.). However, despite the fact the neurotransmitter receptors are involved in axonal regeneration, little is known regarding its expression profile. In this project, RT-PCR and qPCR were performed to gain insight into the neurotransmitter receptors present in Ambystoma. Its functional ability was studied by expressing axolotl receptors in Xenopus laevis oocytes by either injection of mRNA or by direct microtransplantation of brain membranes. Oocytes injected with axolotl mRNA expressed ionotropic receptors activated by GABA, aspartate+glycine and kainate, as well as metabotropic receptors activated by acetylcholine and glutamate. Interestingly, we did not see responses following the application of serotonin. Membranes from the axolotl brain were efficiently microtransplanted into Xenopus oocytes and two types of native GABA receptors that differed in the temporal course of their responses and affinities to GABA were observed. Results of this study are necessary for further characterization of axolotl neurotransmitter receptors and may be useful for guiding experiments aimed at understanding activity-dependant limb and CNS regeneration. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Role of an Absolutely Conserved Tryptophan Pair in the Extracellular Domain of Cys-Loop Receptors

DEFF Research Database (Denmark)

Braun, Nina; Lynagh, Timothy; Yu, Rilei

2016-01-01

Cys-loop receptors mediate fast synaptic transmission in the nervous system, and their dysfunction is associated with a number of diseases. While some sequence variability is essential to ensure specific recognition of a chemically diverse set of ligands, other parts of the underlying amino acid...... sequences show a high degree of conservation, possibly to preserve the overall structural fold across the protein family. In this study, we focus on the only two absolutely conserved residues across the Cys-loop receptor family, two Trp side chains in the WXD motif of Loop D and in the WXPD motif of Loop A...

Ensuring Data Storage Security in Tree cast Routing Architecture for Sensor Networks

Science.gov (United States)

Kumar, K. E. Naresh; Sagar, U. Vidya; Waheed, Mohd. Abdul

2010-10-01

In this paper presents recent advances in technology have made low-cost, low-power wireless sensors with efficient energy consumption. A network of such nodes can coordinate among themselves for distributed sensing and processing of certain data. For which, we propose an architecture to provide a stateless solution in sensor networks for efficient routing in wireless sensor networks. This type of architecture is known as Tree Cast. We propose a unique method of address allocation, building up multiple disjoint trees which are geographically inter-twined and rooted at the data sink. Using these trees, routing messages to and from the sink node without maintaining any routing state in the sensor nodes is possible. In contrast to traditional solutions, where the IT services are under proper physical, logical and personnel controls, this routing architecture moves the application software and databases to the large data centers, where the management of the data and services may not be fully trustworthy. This unique attribute, however, poses many new security challenges which have not been well understood. In this paper, we focus on data storage security, which has always been an important aspect of quality of service. To ensure the correctness of users' data in this architecture, we propose an effective and flexible distributed scheme with two salient features, opposing to its predecessors. By utilizing the homomorphic token with distributed verification of erasure-coded data, our scheme achieves the integration of storage correctness insurance and data error localization, i.e., the identification of misbehaving server(s). Unlike most prior works, the new scheme further supports secure and efficient dynamic operations on data blocks, including: data update, delete and append. Extensive security and performance analysis shows that the proposed scheme is highly efficient and resilient against Byzantine failure, malicious data modification attack, and even server

Ensuring a Safe Technological Revolution

Science.gov (United States)

2016-12-01

much lower, and the performance gained can dramatically reduce life -cycle costs. Validated cost data are scarce, and accurate AM cost models need to be...reduce costs, minimize obsolescence issues and improve both capability and readi- ness across the entire life cycle of naval systems—including both the...of naval weapon systems. The Navy is actively engaging its various communi- ties to align needs and ensure that AM can be safely acceler- ated and

Randomized Assignments for Barter Exchanges: Fairness vs Efficiency

DEFF Research Database (Denmark)

Fang, Wenyi; Filos-Ratsikas, Aris; Frederiksen, Søren Kristoffer Stiil

2015-01-01

We study fairness and efficiency properties of randomized algorithms for barter exchanges with direct applications to kidney exchange problems. It is well documented that randomization can serve as a tool to ensure fairness among participants. However, in many applications, practical constraints...

Energy-Efficient Power Allocation for MIMO-SVD Systems

KAUST Repository

Sboui, Lokman; Rezki, Zouheir; Alouini, Mohamed-Slim

2017-01-01

In this paper, we address the problem of energyefficient power allocation in MIMO systems. In fact, the widely adopted water-filling power allocation does not ensure the maximization of the energy efficiency (EE). Since the EE maximization is a non

New twist on neuronal insulin receptor signaling in health, disease, and therapeutics.

Science.gov (United States)

Wada, Akihiko; Yokoo, Hiroki; Yanagita, Toshihiko; Kobayashi, Hideyuki

2005-10-01

Long after the pioneering studies documenting the existence of insulin (year 1967) and insulin receptor (year 1978) in brain, the last decade has witnessed extraordinary progress in the understanding of brain region-specific multiple roles of insulin receptor signalings in health and disease. In the hypothalamus, insulin regulates food intake, body weight, peripheral fat deposition, hepatic gluconeogenesis, reproductive endocrine axis, and compensatory secretion of counter-regulatory hormones to hypoglycemia. In the hippocampus, insulin promotes learning and memory, independent of the glucoregulatory effect of insulin. Defective insulin receptor signalings are associated with the dementia in normal aging and patients with age-related neurodegenerative diseases (e.g., Alzheimer's disease); the cognitive impairment can be reversed with systemic administration of insulin in the euglycemic condition. Intranasal administration of insulin enhances memory and mood and decreases body weight in healthy humans, without causing hypoglycemia. In the hypothalamus, insulin-induced activation of the phosphoinositide 3-kinase pathway followed by opening of ATP-sensitive K+ channel has been shown to be related to multiple effects of insulin. However, the precise molecular mechanisms of insulin's pleiotropic effects still remain obscure. More importantly, much remains unknown about the quality control mechanisms ensuring correct conformational maturation of the insulin receptor, and the cellular mechanisms regulating density of cell surface functional insulin receptors.

Ensuring the Environmental and Industrial Safety in Solid Mineral Deposit Surface Mining

Science.gov (United States)

Trubetskoy, Kliment; Rylnikova, Marina; Esina, Ekaterina

2017-11-01

The growing environmental pressure of mineral deposit surface mining and severization of industrial safety requirements dictate the necessity of refining the regulatory framework governing safe and efficient development of underground resources. The applicable regulatory documentation governing the procedure of ore open-pit wall and bench stability design for the stage of pit reaching its final boundary was issued several decades ago. Over recent decades, mining and geomechanical conditions have changed significantly in surface mining operations, numerous new software packages and computer developments have appeared, opportunities of experimental methods of source data collection and processing, grounding of the permissible parameters of open pit walls have changed dramatically, and, thus, methods of risk assessment have been perfected [10-13]. IPKON RAS, with the support of the Federal Service for Environmental Supervision, assumed the role of the initiator of the project for the development of Federal norms and regulations of industrial safety "Rules for ensuring the stability of walls and benches of open pits, open-cast mines and spoil banks", which contribute to the improvement of economic efficiency and safety of mineral deposit surface mining and enhancement of the competitiveness of Russian mines at the international level that is very important in the current situation.

Receptor-mediated gene delivery using chemically modified chitosan

International Nuclear Information System (INIS)

Kim, T H; Jiang, H L; Nah, J W; Cho, M H; Akaike, T; Cho, C S

2007-01-01

Chitosan has been investigated as a non-viral vector because it has several advantages such as biocompatibility, biodegradability and low toxicity with high cationic potential. However, the low specificity and low transfection efficiency of chitosan need to be solved prior to clinical application. In this paper, we focused on the galactose or mannose ligand modification of chitosan for enhancement of cell specificity and transfection efficiency via receptor-mediated endocytosis in vitro and in vivo

Rapid and efficient radiosynthesis of [{sup 123}I]I-PK11195, a single photon emission computed tomography tracer for peripheral benzodiazepine receptors

Energy Technology Data Exchange (ETDEWEB)

Pimlott, Sally L. [Department of Clinical Physics, West of Scotland Radionuclide Dispensary, Western Infirmary, G11 6NT Glasgow (United Kingdom)], E-mail: s.pimlott@clinmed.gla.ac.uk; Stevenson, Louise [Department of Chemistry, WestCHEM, University of Glasgow, G12 8QQ Glasgow (United Kingdom); Wyper, David J. [Institute of Neurological Sciences, Southern General Hospital, G51 4TF Glasgow (United Kingdom); Sutherland, Andrew [Department of Chemistry, WestCHEM, University of Glasgow, G12 8QQ Glasgow (United Kingdom)

2008-07-15

Introduction: [{sup 123}I]I-PK11195 is a high-affinity single photon emission computed tomography radiotracer for peripheral benzodiazepine receptors that has previously been used to measure activated microglia and to assess neuroinflammation in the living human brain. This study investigates the radiosynthesis of [{sup 123}I]I-PK11195 in order to develop a rapid and efficient method that obtains [{sup 123}I]I-PK11195 with a high specific activity for in vivo animal and human imaging studies. Methods: The synthesis of [{sup 123}I]I-PK11195 was evaluated using a solid-state interhalogen exchange method and an electrophilic iododestannylation method, where bromine and trimethylstannyl derivatives were used as precursors, respectively. In the electrophilic iododestannylation method, the oxidants peracetic acid and chloramine-T were both investigated. Results: Electrophilic iododestannylation produced [{sup 123}I]I-PK11195 with a higher isolated radiochemical yield and a higher specific activity than achievable using the halogen exchange method investigated. Using chloramine-T as oxidant provided a rapid and efficient method of choice for the synthesis of [{sup 123}I]I-PK11195. Conclusions: [{sup 123}I]I-PK11195 has been successfully synthesized via a rapid and efficient electrophilic iododestannylation method, producing [{sup 123}I]I-PK11195 with a higher isolated radiochemical yield and a higher specific activity than previously achieved.

Indicators System Creation For The Energy Efficiency Benchmarking Of Municipal Power System Facilities

Directory of Open Access Journals (Sweden)

Davydenko L.V.

2015-04-01

Full Text Available The issues of the dataware of the comparative analysis procedure (benchmarking for municipal power system facilities energy efficiency level estimation with a view of the hierarchical structure of the heat supply system are considered. The aim of the paper is the system of indicators formation for characterizing the efficiency of energy usage as on objects on lowest so on highest levels of power systems, proceeding from features of their functioning. Benchmarking methodology allows carrying out the estimation of energy efficiency level on the base of a plurality of parameters without their generalization in one indicator, but requires ensuring their comparability. Using the methodology of available statistical information that did not require deep specification and additional inspection structuring objectives and tasks of energy efficiency estimation problem has been proposed for ensuring the opportunity of benchmarking procedure implementation. This makes it possible to form the subset of indicators that ensure enough specification of the object of study, taking into account the degree of abstraction for every hierarchical level or sub problem. For a comparative analysis of energy using efficiency in municipal power systems at the highest levels of the hierarchy a plurality of indicators of the energy efficiency has been formed. Indicators have been determined with consideration of the structural elements of heat supply systems, but allowing taking into account the efficiency of the initial state of the objects, their functioning, and the questions of energy resources accounting organization. Usage of the proposed indicators provides implementation of energy using efficiency monitoring in the municipal power system and allows getting complete overview of the problem.

Ensuring Microbiological Safety of Fresh Eggs by Using Gamma Irradiation

International Nuclear Information System (INIS)

Hammad, A. A.; Swailam, H.M.; Aly, W. F.

2008-01-01

Egg shell sanitizing practices are necessary to improve microbiological safety of fresh eggs. In this work, fifteen fresh eggs samples of each (Balady, White and Brown eggs) were collected from different local supermarkets to evaluate their microbiological quality. The results indicated that Balady eggs were higher in microbial population in comparison with the two other varieties. Salmonella spp. was detected in 9 (60%) samples of Balady eggs. The effect of gamma irradiation at dose of 0, 2, 3 and 4 kGy on microbiological quality of Balady eggs during storage at 4±1 degree C for 35 days was studied. The effects of irradiation and storage on total cholesterol, and total carotenoids contents in Balady eggs were also investigated. The results showed that irradiation at 3 kGy reduced total aerobic bacterial counts. Coliform bacteria, E. coli and Salmonella spp. were completely eliminated. Total cholesterol and total carotenoids were decreased in yolk egg as a result of irradiation. Treated Balady eggs with irradiation dose of 3 kGy were efficient and sufficient for ensuring safety, maintain quality and extend shelf-life.

A cleavable signal peptide enhances cell surface delivery and heterodimerization of Cerulean-tagged angiotensin II AT1 and bradykinin B2 receptor

International Nuclear Information System (INIS)

Quitterer, Ursula; Pohl, Armin; Langer, Andreas; Koller, Samuel; AbdAlla, Said

2011-01-01

Highlights: → A new FRET-based method detects AT1/B2 receptor heterodimerization. → First time application of AT1-Cerulean as a FRET donor. → Method relies on signal peptide-enhanced cell surface delivery of AT1-Cerulean. → A high FRET efficiency revealed efficient heterodimerization of AT1/B2R proteins. → AT1/B2R heterodimers were functionally coupled to desensitization mechanisms. -- Abstract: Heterodimerization of the angiotensin II AT1 receptor with the receptor for the vasodepressor bradykinin, B2R, is known to sensitize the AT1-stimulated response of hypertensive individuals in vivo. To analyze features of that prototypic receptor heterodimer in vitro, we established a new method that uses fluorescence resonance energy transfer (FRET) and applies for the first time AT1-Cerulean as a FRET donor. The Cerulean variant of the green fluorescent protein as donor fluorophore was fused to the C-terminus of AT1, and the enhanced yellow fluorescent protein (EYFP) as acceptor fluorophore was fused to B2R. In contrast to AT1-EGFP, the AT1-Cerulean fusion protein was retained intracellularly. To facilitate cell surface delivery of AT1-Cerulean, a cleavable signal sequence was fused to the receptor's amino terminus. The plasma membrane-localized AT1-Cerulean resembled the native AT1 receptor regarding ligand binding and receptor activation. A high FRET efficiency of 24.7% between membrane-localized AT1-Cerulean and B2R-EYFP was observed with intact, non-stimulated cells. Confocal FRET microscopy further revealed that the AT1/B2 receptor heterodimer was functionally coupled to receptor desensitization mechanisms because activation of the AT1-Cerulean/B2R-EYFP heterodimer with a single agonist triggered the co-internalization of AT1/B2R. Receptor co-internalization was sensitive to inhibition of G protein-coupled receptor kinases, GRKs, as evidenced by a GRK-specific peptide inhibitor. In agreement with efficient AT1/B2R heterodimerization, confocal FRET imaging of

A cleavable signal peptide enhances cell surface delivery and heterodimerization of Cerulean-tagged angiotensin II AT1 and bradykinin B2 receptor

Energy Technology Data Exchange (ETDEWEB)

Quitterer, Ursula, E-mail: ursula.quitterer@pharma.ethz.ch [Molecular Pharmacology Unit, Swiss Federal Institute of Technology and University of Zurich, Zurich (Switzerland); Pohl, Armin; Langer, Andreas; Koller, Samuel; AbdAlla, Said [Molecular Pharmacology Unit, Swiss Federal Institute of Technology and University of Zurich, Zurich (Switzerland)

2011-06-10

Highlights: {yields} A new FRET-based method detects AT1/B2 receptor heterodimerization. {yields} First time application of AT1-Cerulean as a FRET donor. {yields} Method relies on signal peptide-enhanced cell surface delivery of AT1-Cerulean. {yields} A high FRET efficiency revealed efficient heterodimerization of AT1/B2R proteins. {yields} AT1/B2R heterodimers were functionally coupled to desensitization mechanisms. -- Abstract: Heterodimerization of the angiotensin II AT1 receptor with the receptor for the vasodepressor bradykinin, B2R, is known to sensitize the AT1-stimulated response of hypertensive individuals in vivo. To analyze features of that prototypic receptor heterodimer in vitro, we established a new method that uses fluorescence resonance energy transfer (FRET) and applies for the first time AT1-Cerulean as a FRET donor. The Cerulean variant of the green fluorescent protein as donor fluorophore was fused to the C-terminus of AT1, and the enhanced yellow fluorescent protein (EYFP) as acceptor fluorophore was fused to B2R. In contrast to AT1-EGFP, the AT1-Cerulean fusion protein was retained intracellularly. To facilitate cell surface delivery of AT1-Cerulean, a cleavable signal sequence was fused to the receptor's amino terminus. The plasma membrane-localized AT1-Cerulean resembled the native AT1 receptor regarding ligand binding and receptor activation. A high FRET efficiency of 24.7% between membrane-localized AT1-Cerulean and B2R-EYFP was observed with intact, non-stimulated cells. Confocal FRET microscopy further revealed that the AT1/B2 receptor heterodimer was functionally coupled to receptor desensitization mechanisms because activation of the AT1-Cerulean/B2R-EYFP heterodimer with a single agonist triggered the co-internalization of AT1/B2R. Receptor co-internalization was sensitive to inhibition of G protein-coupled receptor kinases, GRKs, as evidenced by a GRK-specific peptide inhibitor. In agreement with efficient AT1/B2R

Structure–property relationships of oligothiophene–isoindigo polymers for efficient bulk-heterojunction solar cells

KAUST Repository

Ma, Zaifei; Sun, Wenjun; Himmelberger, Scott; Vandewal, Koen; Tang, Zheng; Bergqvist, Jonas; Salleo, Alberto; Andreasen, Jens Wenzel; Inganä s, Olle; Andersson, Mats R.; Mü ller, Christian; Zhang, Fengling; Wang, Ergang

2014-01-01

performance with a power conversion efficiency of up to 6.9% was achieved with devices based on P3TI, where a combination of a favorable morphology and an optimal interfacial energy level offset ensures efficient exciton separation and charge generation

Efficient silkworm expression of human GPCR (nociceptin receptor) by a Bombyx mori bacmid DNA system

Energy Technology Data Exchange (ETDEWEB)

Kajikawa, Mizuho; Sasaki, Kaori [Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Wakimoto, Yoshitaro; Toyooka, Masaru [Department of Chemistry and Chemical Biology, Graduate School of Engineering, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma 376-8515 (Japan); Motohashi, Tomoko; Shimojima, Tsukasa [National Institute of Genetics, 1111 Yata, Mishima, Shizuoka 411-8540 (Japan); Takeda, Shigeki [Department of Chemistry and Chemical Biology, Graduate School of Engineering, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma 376-8515 (Japan); Park, Enoch Y. [Laboratory of Biotechnology, Integrated Bioscience Section, Graduate School of Science and Technology, Shizuoka University, 836 Oya, Suruga-ku, Shizuoka, Shizuoka 422-8529 (Japan); Maenaka, Katsumi, E-mail: kmaenaka-umin@umin.net [Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan)

2009-07-31

Guanine nucleotide-binding protein (G protein) coupled receptors (GPCRs) are frequently expressed by a baculovirus expression vector system (BEVS). We recently established a novel BEVS using the bacmid system of Bombyx mori nucleopolyhedrovirus (BmNPV), which is directly applicable for protein expression in silkworms. Here, we report the first example of GPCR expression in silkworms by the simple injection of BmNPV bacmid DNA. Human nociceptin receptor, an inhibitory GPCR, and its fusion protein with inhibitory G protein alpha subunit (G{sub i}{alpha}) were both successfully expressed in the fat bodies of silkworm larvae as well as in the BmNPV viral fraction. Its yield was much higher than that from Sf9 cells. The microsomal fractions including the nociceptin receptor fusion, which are easily prepared by only centrifugation steps, exhibited [{sup 35}S]GTP{gamma}S-binding activity upon specific stimulation by nociceptin. Therefore, this rapid method is easy-to-use and has a high expression level, and thus will be an important tool for human GPCR production.

Virtual Screening of Receptor Sites for Molecularly Imprinted Polymers.

Science.gov (United States)

Bates, Ferdia; Cela-Pérez, María Concepción; Karim, Kal; Piletsky, Sergey; López-Vilariño, José Manuel

2016-08-01

Molecularly Imprinted Polymers (MIPs) are highly advantageous in the field of analytical chemistry. However, interference from secondary molecules can also impede capture of a target by a MIP receptor. This greatly complicates the design process and often requires extensive laboratory screening which is time consuming, costly, and creates substantial waste products. Herein, is presented a new technique for screening of "virtually imprinted receptors" for rebinding of the molecular template as well as secondary structures, correlating the virtual predictions with experimentally acquired data in three case studies. This novel technique is particularly applicable to the evaluation and prediction of MIP receptor specificity and efficiency in complex aqueous systems. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Characterization of the single transmembrane domain of human receptor activity-modifying protein 3 in adrenomedullin receptor internalization

International Nuclear Information System (INIS)

Kuwasako, Kenji; Kitamura, Kazuo; Nagata, Sayaka; Nozaki, Naomi; Kato, Johji

2012-01-01

Highlights: ► RAMP3 mediates CLR internalization much less effectively than does RAMP2. ► The RAMP3 TMD participates in the negative regulation of CLR/RAMP3 internalization. ► A new strategy of promoting internalization and resensitization of the receptor was found. -- Abstract: Two receptor activity-modifying proteins (RAMP2 and RAMP3) enable calcitonin receptor-like receptor (CLR) to function as two heterodimeric receptors (CLR/RAMP2 and CLR/RAMP3) for adrenomedullin (AM), a potent cardiovascular protective peptide. Following AM stimulation, both receptors undergo rapid internalization through a clathrin-dependent pathway, after which CLR/RAMP3, but not CLR/RAMP2, can be recycled to the cell surface for resensitization. However, human (h)RAMP3 mediates CLR internalization much less efficiently than does hRAMP2. Therefore, the molecular basis of the single transmembrane domain (TMD) and the intracellular domain of hRAMP3 during AM receptor internalization was investigated by transiently transfecting various RAMP chimeras and mutants into HEK-293 cells stably expressing hCLR. Flow cytometric analysis revealed that substituting the RAMP3 TMD with that of RAMP2 markedly enhanced AM-induced internalization of CLR. However, this replacement did not enhance the cell surface expression of CLR, [ 125 I]AM binding affinity or AM-induced cAMP response. More detailed analyses showed that substituting the Thr 130 –Val 131 sequence in the RAMP3 TMD with the corresponding sequence (Ile 157 –Pro 158 ) from RAMP2 significantly enhanced AM-mediated CLR internalization. In contrast, substituting the RAMP3 target sequence with Ala 130 –Ala 131 did not significantly affect CLR internalization. Thus, the RAMP3 TMD participates in the negative regulation of CLR/RAMP3 internalization, and the aforementioned introduction of the Ile–Pro sequence into the RAMP3 TMD may be a strategy for promoting receptor internalization/resensitization.

Adult forebrain NMDA receptors gate social motivation and social memory.

Science.gov (United States)

Jacobs, Stephanie; Tsien, Joe Z

2017-02-01

Motivation to engage in social interaction is critical to ensure normal social behaviors, whereas dysregulation in social motivation can contribute to psychiatric diseases such as schizophrenia, autism, social anxiety disorders and post-traumatic stress disorder (PTSD). While dopamine is well known to regulate motivation, its downstream targets are poorly understood. Given the fact that the dopamine 1 (D1) receptors are often physically coupled with the NMDA receptors, we hypothesize that the NMDA receptor activity in the adult forebrain principal neurons are crucial not only for learning and memory, but also for the proper gating of social motivation. Here, we tested this hypothesis by examining sociability and social memory in inducible forebrain-specific NR1 knockout mice. These mice are ideal for exploring the role of the NR1 subunit in social behavior because the NR1 subunit can be selectively knocked out after the critical developmental period, in which NR1 is required for normal development. We found that the inducible deletion of the NMDA receptors prior to behavioral assays impaired, not only object and social recognition memory tests, but also resulted in profound deficits in social motivation. Mice with ablated NR1 subunits in the forebrain demonstrated significant decreases in sociability compared to their wild type counterparts. These results suggest that in addition to its crucial role in learning and memory, the NMDA receptors in the adult forebrain principal neurons gate social motivation, independent of neuronal development. Copyright © 2016 Elsevier Inc. All rights reserved.

(indigenous) education ensure effective gender mainstreaming in ...

African Journals Online (AJOL)

Leaving no one behind: can (indigenous) education ensure effective gender ... in the distribution of socio-economic and political benefits, depict that additional ... of gender equality and equity and explores in different ways the relationships ...

Comparison of lentiviral and sleeping beauty mediated αβ T cell receptor gene transfer.

Directory of Open Access Journals (Sweden)

Anne-Christine Field

Full Text Available Transfer of tumour antigen-specific receptors to T cells requires efficient delivery and integration of transgenes, and currently most clinical studies are using gamma retroviral or lentiviral systems. Whilst important proof-of-principle data has been generated for both chimeric antigen receptors and αβ T cell receptors, the current platforms are costly, time-consuming and relatively inflexible. Alternative, more cost-effective, Sleeping Beauty transposon-based plasmid systems could offer a pathway to accelerated clinical testing of a more diverse repertoire of recombinant high affinity T cell receptors. Nucleofection of hyperactive SB100X transposase-mediated stable transposition of an optimised murine-human chimeric T cell receptor specific for Wilm's tumour antigen from a Sleeping Beauty transposon plasmid. Whilst transfer efficiency was lower than that mediated by lentiviral transduction, cells could be readily enriched and expanded, and mediated effective target cells lysis in vitro and in vivo. Integration sites of transposed TCR genes in primary T cells were almost randomly distributed, contrasting the predilection of lentiviral vectors for transcriptionally active sites. The results support exploitation of the Sleeping Beauty plasmid based system as a flexible and adaptable platform for accelerated, early-phase assessment of T cell receptor gene therapies.

Achieving palliative care research efficiency through defining and benchmarking performance metrics.

Science.gov (United States)

Lodato, Jordan E; Aziz, Noreen; Bennett, Rachael E; Abernethy, Amy P; Kutner, Jean S

2012-12-01

Research efficiency is gaining increasing attention in the research enterprise, including palliative care research. The importance of generating meaningful findings and translating these scientific advances to improved patient care creates urgency in the field to address well documented system inefficiencies. The Palliative Care Research Cooperative Group (PCRC) provides useful examples for ensuring research efficiency in palliative care. Literature on maximizing research efficiency focuses on the importance of clearly delineated process maps, working instructions, and standard operating procedures in creating synchronicity in expectations across research sites. Examples from the PCRC support these objectives and suggest that early creation and employment of performance metrics aligned with these processes are essential to generate clear expectations and identify benchmarks. These benchmarks are critical in effective monitoring and ultimately the generation of high-quality findings that are translatable to clinical populations. Prioritization of measurable goals and tasks to ensure that activities align with programmatic aims is critical. Examples from the PCRC affirm and expand the existing literature on research efficiency, providing a palliative care focus. Operating procedures, performance metrics, prioritization, and monitoring for success should all be informed by and inform the process map to achieve maximum research efficiency.

An evaluation of adequacy of water policy stipulation in ensuring ...

African Journals Online (AJOL)

An evaluation of adequacy of water policy stipulation in ensuring water security in the context of climate change. ... Ethiopian Journal of Environmental Studies and Management ... The aim of the study was to establish how responsive the Water Policy (2010) is to ensure water security in the context of climate change.

Energy efficient process planning based on numerical simulations

OpenAIRE

Neugebauer, Reimund; Hochmuth, C.; Schmidt, G.; Dix, M.

2011-01-01

The main goal of energy-efficient manufacturing is to generate products with maximum value-added at minimum energy consumption. To this end, in metal cutting processes, it is necessary to reduce the specific cutting energy while, at the same time, precision requirements have to be ensured. Precision is critical in metal cutting processes because they often constitute the final stages of metalworking chains. This paper presents a method for the planning of energy-efficient machining processes ...

CREATIV: Research-based innovation for industry energy efficiency

International Nuclear Information System (INIS)

Tangen, Grethe; Hemmingsen, Anne Karin T.; Neksa, Petter

2011-01-01

Improved energy efficiency is imperative to minimise the greenhouse gas emissions and to ensure future energy security. It is also a key to continued profitability in energy consuming industry. The project CREATIV is a research initiative for industry energy efficiency focusing on utilisation of surplus heat and efficient heating and cooling. In CREATIV, international research groups work together with key vendors of energy efficiency equipment and an industry consortium including the areas metallurgy, pulp and paper, food and fishery, and commercial refrigeration supermarkets. The ambition of CREATIV is to bring forward technology and solutions enabling Norway to reduce both energy consumption and greenhouse gas emissions by 25% within 2020. The main research topics are electricity production from low temperature heat sources in supercritical CO 2 cycles, energy efficient end-user technology for heating and cooling based on natural working fluids and system optimisation, and efficient utilisation of low temperature heat by developing new sorption systems and compact compressor-expander units. A defined innovation strategy in the project will ensure exploitation of research results and promote implementation in industry processes. CREATIV will contribute to the recruitment of competent personnel to industry and academia by educating PhD and post doc candidates and several MSc students. The paper presents the CREATIV project, discusses its scientific achievements so far, and outlines how the project results can contribute to reducing industry energy consumption. - Highlights: → New technology for improved energy efficiency relevant across several industries. → Surplus heat exploitation and efficient heating and cooling are important means. → Focus on power production from low temperature heat and heat pumping technologies. → Education and competence building are given priority. → The project consortium includes 20 international industry companies and

Identification and Transcriptional Modulation of the Largemouth Bass, Micropterus salmoides, Vitellogenin Receptor During Oocyte Development by Insulin and Sex Steroids1

OpenAIRE

Dominguez, Gustavo A.; Quattro, Joseph M.; Denslow, Nancy D.; Kroll, Kevin J.; Prucha, Melinda S.; Porak, Wesley F.; Grier, Harry J.; Sabo-Attwood, Tara L.

2012-01-01

Fish vitellogenin synthesized and released from the liver of oviparous animals is taken up into oocytes by the vitellogenin receptor. This is an essential process in providing nutrient yolk to developing embryos to ensure successful reproduction. Here we disclose the full length vtgr cDNA sequence for largemouth bass (LMB) that reveals greater than 90% sequence homology with other fish vtgr sequences. We classify LMB Vtgr as a member of the low density lipoprotein receptor superfamily based o...

The SEAD global efficiency medal competition: accelerating market transformation for efficient televisions

Energy Technology Data Exchange (ETDEWEB)

Ravi, Kavita [US Department of Energy, Washington, DC (United States); Bennich, Peter [Swedish Energy Agency (Sweden); Cockburn, John [Natural Resources Canada, Ottawa (Canada); Doi, Naoko [Institute of Energy Economics (Japan); Garg, Sandeep [United Nations Development Programme, New York, NY (United States); Garnaik, S.P. [ICF International (India); Holt, Shane [Energy and Tourism, Canberra (Australia); Walker, Mike [Food and Rural Affairs (United Kingdom); Westbrook-Trenholm, Elizabeth [Natural Resources, Canada, Ottawa (Canada). Office of Energy Efficiency; Lising, Anna [Collaborative Labeling and Appliance Standards Program (United States); Pantano, Steve [Collaborative Labeling and Appliance Standards Program (United States); Khare, Amit [Collaborative Labeling and Appliance Standards Program (United States); Park, Won Young [Lawrence Berkeley National Lab., CA (United States)

2013-10-15

The Global Efficiency Medal competition, a cornerstone activity of the Super-efficient Equipment and Appliance Deployment (SEAD) Initiative, is an awards program that encourages the production and sale of super-efficient products. SEAD is a voluntary multinational government collaboration of the Clean Energy Ministerial (CEM). This winner-takes-all competition recognizes products with the best energy efficiency, guides early adopter purchasers towards the most efficient product choices and demonstrates the levels of energy efficiency achievable by commercially available and emerging technologies. The first Global Efficiency Medals were awarded to the most energy-efficient flat panel televisions; an iconic consumer purchase. SEAD Global Efficiency Medals were awarded to televisions that have proven to be substantially more energy efficient than comparable models available at the time of the competition (applications closed in the end of May 2012). The award-winning TVs consume between 33 to 44 percent less energy per 2 unit of screen area than comparable LED-backlit LCD televisions sold in each regional market and 50 to 60 percent less energy than CCFL-backlit LCD TVs. Prior to the launch of this competition, SEAD conducted an unprecedented international round-robin test (RRT) to qualify TV test laboratories to support verification testing for SEAD awards. The RRT resulted in increased test laboratory capacity and expertise around the world and ensured that the test results from participating regional test laboratories could be compared in a fair and transparent fashion. This paper highlights a range of benefits resulting from this first SEAD awards competition and encourages further investigation of the awards concept as a means to promote energy efficiency in other equipment types.

Efficient Windows Collaborative

Energy Technology Data Exchange (ETDEWEB)

Nils Petermann

2010-02-28

The project goals covered both the residential and commercial windows markets and involved a range of audiences such as window manufacturers, builders, homeowners, design professionals, utilities, and public agencies. Essential goals included: (1) Creation of 'Master Toolkits' of information that integrate diverse tools, rating systems, and incentive programs, customized for key audiences such as window manufacturers, design professionals, and utility programs. (2) Delivery of education and outreach programs to multiple audiences through conference presentations, publication of articles for builders and other industry professionals, and targeted dissemination of efficient window curricula to professionals and students. (3) Design and implementation of mechanisms to encourage and track sales of more efficient products through the existing Window Products Database as an incentive for manufacturers to improve products and participate in programs such as NFRC and ENERGY STAR. (4) Development of utility incentive programs to promote more efficient residential and commercial windows. Partnership with regional and local entities on the development of programs and customized information to move the market toward the highest performing products. An overarching project goal was to ensure that different audiences adopt and use the developed information, design and promotion tools and thus increase the market penetration of energy efficient fenestration products. In particular, a crucial success criterion was to move gas and electric utilities to increase the promotion of energy efficient windows through demand side management programs as an important step toward increasing the market share of energy efficient windows.

Methodological Approaches to Ensuring Innovative Development of Metallurgical Enterprises on the Basis of Principles of Economic Nationalism

Directory of Open Access Journals (Sweden)

Denysov Kostyantyn V.

2017-01-01

Full Text Available The economic, energy and environmental aspects of the activities of metallurgical enterprises are analyzed in the context of the need to ensure their sustainable development. The high energy intensity of the production process, the low efficiency and irrational structure of capital expenditures for environmental protection, the dominance of material costs in the final cost of finished products at the expense of labor and social contributions are indicated. There proved the low effectiveness of the previous measures of the industrial policy of the metallurgical industry innovative development that were not in compliance with the requirements of the WTO and led to taking compensatory measures against the Ukrainian steel on world markets. The potential of economic nationalism as a system for ensuring the innovative development of the metallurgical industry is considered. There determined the priorities of the industrial policy for the development of metallurgical enterprises based on the principles of economic nationalism and taking into account the global trends in the development of trade and economic relations and Ukraine’s commitments to the WTO.

Methods for ensuring compliance with regulatory requirements: regulators and operators

International Nuclear Information System (INIS)

Fleischmann, A.W.

1989-01-01

Some of the methods of ensuring compliance with regulatory requirements contained in various radiation protection documents such as Regulations, ICRP Recommendations etc. are considered. These include radiation safety officers and radiation safety committees, personnel monitoring services, dissemination of information, inspection services and legislative power of enforcement. Difficulties in ensuring compliance include outmoded legislation, financial and personnel constraints

Receptors for Projection Radiography. Chapter 7

Energy Technology Data Exchange (ETDEWEB)

Rowlands, J. A. [Thunder Bay Regional Research Institute, Thunder Bay (Canada); Neitzel, U. [Philips Healthcare, Hamburg (Germany)

2014-09-15

X ray images are formed as shadows of the interior of the body. Since it is not yet practical to focus X rays, an X ray receptor has to be larger than the body part to be imaged. Thus, the first challenge in making an X ray receptor is the need to image a large area. A second challenge is to make a system that has an image quality as good as that allowed by the physics, i.e. permits the detection of objects whose size and contrast are limited only by the quantum statistics (see Section 4.6). This means absorbing most of the X ray quanta and using these in an efficient, i.e. a quantum noise limited, manner, while providing adequate spatial resolution simultaneously.

Developing a System for Directed Gene Introduction into Mammary Gland Via Targeted Infection of Retrovirus Receptor Transgenics

National Research Council Canada - National Science Library

Bates, Paul

1998-01-01

... (the Rous sarcoma virus receptor). Directed infection, and thus directed gene expression of cells expressing the viral receptor should provide a rapid and efficient method to test the mammary tumorigenic potential of genes in an animal model...

The Motion of a Single Molecule, the Lambda-Receptor, in the Bacterial Outer Membrane

DEFF Research Database (Denmark)

Oddershede, Lene; Dreyer, Jakob Kisbye; Grego, Sonia

2002-01-01

Using optical tweezers and single particle tracking, we have revealed the motion of a single protein, the lambda-receptor, in the outer membrane of living Escherichia coli bacteria. We genetically modified the lambda-receptor placing a biotin on an extracellular site of the receptor in vivo....... The efficiency of this in vivo biotinylation is very low, thus enabling the attachment of a streptavidin-coated bead binding specifically to a single biotinylated lambda-receptor. The bead was used as a handle for the optical tweezers and as a marker for the single particle tracking routine. We propose a model...

Recruitment of activation receptors at inhibitory NK cell immune synapses.

Directory of Open Access Journals (Sweden)

Nicolas Schleinitz

2008-09-01

Full Text Available Natural killer (NK cell activation receptors accumulate by an actin-dependent process at cytotoxic immune synapses where they provide synergistic signals that trigger NK cell effector functions. In contrast, NK cell inhibitory receptors, including members of the MHC class I-specific killer cell Ig-like receptor (KIR family, accumulate at inhibitory immune synapses, block actin dynamics, and prevent actin-dependent phosphorylation of activation receptors. Therefore, one would predict inhibition of actin-dependent accumulation of activation receptors when inhibitory receptors are engaged. By confocal imaging of primary human NK cells in contact with target cells expressing physiological ligands of NK cell receptors, we show here that this prediction is incorrect. Target cells included a human cell line and transfected Drosophila insect cells that expressed ligands of NK cell activation receptors in combination with an MHC class I ligand of inhibitory KIR. The two NK cell activation receptors CD2 and 2B4 accumulated and co-localized with KIR at inhibitory immune synapses. In fact, KIR promoted CD2 and 2B4 clustering, as CD2 and 2B4 accumulated more efficiently at inhibitory synapses. In contrast, accumulation of KIR and of activation receptors at inhibitory synapses correlated with reduced density of the integrin LFA-1. These results imply that inhibitory KIR does not prevent CD2 and 2B4 signaling by blocking their accumulation at NK cell immune synapses, but by blocking their ability to signal within inhibitory synapses.

Compositions and methods related to serotonin 5-HT1A receptors

Science.gov (United States)

Mukherjee, Jogeshwar [Irvine, CA; Saigal, Neil [Fresno, CA; Saigal, legal representative, Harsh

2012-09-25

Contemplated substituted arylpiperazinyl compounds, and most preferably .sup.18F-Mefway, exhibit desirable in vitro and in vivo binding characteristics to the 5-HT1A receptor. Among other advantageous parameters, contemplated compounds retain high binding affinity, display optimal lipophilicity, and are radiolabeled efficiently with .sup.18F-fluorine in a single step. Still further, contemplated compounds exhibit high target to non-target ratios in receptor-rich regions both in vitro and in vivo, and selected compounds can be effectively and sensitively displaced by serotonin, thus providing a quantitative tool for measuring 5-HT1A receptors and serotonin concentration changes in the living brain.

New methods in efficient coal transportation

Energy Technology Data Exchange (ETDEWEB)

Monroe, C.O.; Wolach, D.G.; Alexander, A.B. [Savage Industries Inc., Salt Lake City, UT (United States)

1998-10-01

With the increasing trend towards railroad mergers in the USA, there is a growing awareness of competition and of the need for railroads to ensure a better value service. This paper discusses the concept of business process outsourcing and its potential to provide an efficient and integrated transport system for coal handling. Examples at US coal distribution facilities are given. 6 photos., 1 fig.

Cell-surface acceleration of urokinase-catalyzed receptor cleavage

DEFF Research Database (Denmark)

Høyer-Hansen, G; Ploug, M; Behrendt, N

1997-01-01

by a prior incubation of the cells with uPA inactivated by diisopropyl fluorophosphate, demonstrating a requirement for specific receptor binding of the active uPA to obtain the high-efficiency cleavage of cell-bound uPAR. Furthermore, amino-terminal sequence analysis revealed that uPAR(2+3), purified from U...

Targeting transferrin receptors at the blood-brain barrier improves the uptake of immunoliposomes and subsequent cargo transport into the brain parenchyma

DEFF Research Database (Denmark)

Johnsen, Kasper B.; Burkhart, Annette; Melander, Fredrik

2017-01-01

Drug delivery to the brain is hampered by the presence of the blood-brain barrier, which excludes most molecules from freely diffusing into the brain, and tightly regulates the active transport mechanisms that ensure sufficient delivery of nutrients to the brain parenchyma. Harnessing...... the possibility of delivering neuroactive drugs by way of receptors already present on the brain endothelium has been of interest for many years. The transferrin receptor is of special interest since its expression is limited to the endothelium of the brain as opposed to peripheral endothelium. Here, we...... investigate the possibility of delivering immunoliposomes and their encapsulated cargo to the brain via targeting of the transferrin receptor. We find that transferrin receptor-targeting increases the association between the immunoliposomes and primary endothelial cells in vitro, but that this does...

Megalin functions as an endocytic sonic hedgehog receptor.

Science.gov (United States)

McCarthy, Robert A; Barth, Jeremy L; Chintalapudi, Mastan R; Knaak, Christian; Argraves, W Scott

2002-07-12

Embryos deficient in the morphogen Sonic hedgehog (Shh) or the endocytic receptor megalin exhibit common neurodevelopmental abnormalities. Therefore, we have investigated the possibility that a functional relationship exists between the two proteins. During embryonic development, megalin was found to be expressed along the apical surfaces of neuroepithelial cells and was coexpressed with Shh in the ventral floor plate of the neural tube. Using enzyme-linked immunosorbent assay, homologous ligand displacement, and surface plasmon resonance techniques, it was found that the amino-terminal fragment of Shh (N-Shh) bound to megalin with high affinity. Megalin-expressing cells internalized N-Shh through a mechanism that was inhibited by antagonists of megalin, viz. anti-receptor-associated protein and anti-megalin antibodies. Heparin also inhibited N-Shh endocytosis, implicating proteoglycans in the internalization process, as has been described for other megalin ligands. Use of chloroquine to inhibit lysosomal proteinase activity showed that N-Shh endocytosed via megalin was not efficiently targeted to the lysosomes for degradation. The ability of megalin-internalized N-Shh to bypass lysosomes may relate to the finding that the interaction between N-Shh and megalin was resistant to dissociation with low pH. Together, these findings show that megalin is an efficient endocytic receptor for N-Shh. Furthermore, they implicate megalin as a new regulatory component of the Shh signaling pathway.

Advancing Evidence Based Policymaking and Regulation to Ensure ...

International Development Research Centre (IDRC) Digital Library (Canada)

Advancing Evidence Based Policymaking and Regulation to Ensure Greater ... which is Communications Policy Research South (CPRsouth), a yearly conference that ... policy intellectuals through tutorials for young scholars and internships.

Ensuring long-term availability of TELEPERM XS

International Nuclear Information System (INIS)

Bock, H.-W.; Richter, S.

1998-01-01

With putting in operation the first digital TELEPERM XS I and C systems for functions important to safety in nuclear power plants, ensuring long-term availability and reliable operation of TELEPERM XS systems gains increasing importance. On the one hand, the modular structure of TELEPERM XS has already been optimized during system development such that the application-specific functions are independent of the version of hardware components and system software. On the other hand, hardware-independent, tool-based engineering procedures ensure that the application software of installed I and C systems can be flexibly adapted to modified plant requirements while at the same time the very high software quality is retained. Quality-assured procedures and an actively organized configuration management guarantee that the functionality and the availability of the I and C systems keep their qualified standard. This paper discusses aspects of the configuration management for TELEPERM XS I and C systems. (author)

Efficiency of bitter kola marketing in Abia State, Nigeria | Iheke ...

African Journals Online (AJOL)

Efficiency of bitter kola marketing in Abia State, Nigeria. ... The goal of marketing of agricultural products is to ensure that consumers get satisfaction from the entire process of production, as well as ... EMAIL FULL TEXT EMAIL FULL TEXT

Possible Relevance of Receptor-Receptor Interactions between Viral- and Host-Coded Receptors for Viral-Induced Disease

Directory of Open Access Journals (Sweden)

Luigi F. Agnati

2007-01-01

Full Text Available It has been demonstrated that some viruses, such as the cytomegalovirus, code for G-protein coupled receptors not only to elude the immune system, but also to redirect cellular signaling in the receptor networks of the host cells. In view of the existence of receptor-receptor interactions, the hypothesis is introduced that these viral-coded receptors not only operate as constitutively active monomers, but also can affect other receptor function by interacting with receptors of the host cell. Furthermore, it is suggested that viruses could also insert not single receptors (monomers, but clusters of receptors (receptor mosaics, altering the cell metabolism in a profound way. The prevention of viral receptor-induced changes in host receptor networks may give rise to novel antiviral drugs that counteract viral-induced disease.

Toward Ensuring Health Equity

DEFF Research Database (Denmark)

Petkovic, Jennifer; Epstein, Jonathan; Buchbinder, Rachelle

2015-01-01

, the Evaluative Linguistic Framework for Questionnaires, developed to assess text quality of questionnaires. We also considered a study assessing cross-cultural adaptation with/without back-translation and/or expert committee. The results of this preconference work were presented to the equity working group......OBJECTIVE: The goal of the Outcome Measures in Rheumatology (OMERACT) 12 (2014) equity working group was to determine whether and how comprehensibility of patient-reported outcome measures (PROM) should be assessed, to ensure suitability for people with low literacy and differing cultures. METHODS......: The English, Dutch, French, and Turkish Health Assessment Questionnaires and English and French Osteoarthritis Knee and Hip Quality of Life questionnaires were evaluated by applying 3 readability formulas: Flesch Reading Ease, Flesch-Kincaid grade level, and Simple Measure of Gobbledygook; and a new tool...

Quantitative Impact of Plasma Clearance and Down-regulation on GLP-1 Receptor Molecular Imaging.

Science.gov (United States)

Zhang, Liang; Thurber, Greg M

2016-02-01

Quantitative molecular imaging of beta cell mass (BCM) would enable early detection and treatment monitoring of type 1 diabetes. The glucagon-like peptide-1 (GLP-1) receptor is an attractive target due to its beta cell specificity and cell surface location. We quantitatively investigated the impact of plasma clearance and receptor internalization on targeting efficiency in healthy B6 mice. Four exenatide-based probes were synthesized that varied in molecular weight, binding affinity, and plasma clearance. The GLP-1 receptor internalization rate and in vivo receptor expression were quantified. Receptor internalization (54,000 receptors/cell in vivo) decreased significantly within minutes, reducing the benefit of a slower-clearing agent. The multimers and albumin binding probes had higher kidney and liver uptake, respectively. Slow plasma clearance is beneficial for GLP-1 receptor peptide therapeutics. However, for exendin-based imaging of islets, down-regulation of the GLP-1 receptor and non-specific background uptake result in a higher target-to-background ratio for fast-clearing agents.

Genetic polymorphism of vitamin D receptor determines its metabolism and efficiency

Directory of Open Access Journals (Sweden)

O.A. Yakovleva

2017-04-01

Full Text Available The review represents the results of researches of vitamin D receptor characteristics and its genetic polymorphism, which is variable in different populations, and also depends on age and gender. This polymorphism determines the association of vitamin D different concentration with the probability of bronchial asthma or chronic obstructive pulmonary disease development, and therefore the different efficacy of drug correction of vitamin D deficiency. However, the scientific data are contradictory, the molecular mechanisms of connection between vitamin D and bronchial tonus or allergic reactions remain unclear, which emphasizes the importance of studies to clarify the role of vitamin D in inflammatory, immune disorders in bronchial obstructive syndrome.

The under-appreciated promiscuity of the epidermal growth factor receptor family.

Directory of Open Access Journals (Sweden)

Sean P Kennedy

2016-08-01

Full Text Available Each member of the epidermal growth factor receptor (EGFR family plays a key role in normal development, homeostasis and a variety of pathophysiological conditions, most notably in cancer. According to the prevailing dogma, these four receptor tyrosine kinases (RTKs; EGFR, ERBB2, ERBB3 and ERBB4 function exclusively through the formation of homodimers and heterodimers within the EGFR family. These combinatorial receptor interactions are known to generate increased interactome diversity and therefore influence signalling output, subcellular localization and function of the heterodimer. This molecular plasticity is also thought to play a role in the development of resistance towards targeted cancer therapies aimed at these known oncogenes. Interestingly, many studies now challenge this dogma and suggest that the potential for EGFR family receptors to interact with more distantly related RTKs is much greater than currently appreciated. Here we discuss how the promiscuity of these oncogenic receptors may lead to the formation of many unexpected receptor pairings and the significant implications for the efficiency of many targeted cancer therapies.

Toll-like receptor-2 agonist-allergen coupling efficiently redirects Th2 cell responses and inhibits allergic airway eosinophilia.

Science.gov (United States)

Krishnaswamy, Jayendra Kumar; Jirmo, Adan Chari; Baru, Abdul Mannan; Ebensen, Thomas; Guzmán, Carlos A; Sparwasser, Tim; Behrens, Georg M N

2012-12-01

Toll-like receptor (TLR) agonists beneficially modulate allergic airway inflammation. However, the efficiency of TLR agonists varies considerably, and their exact cellular mechanisms (especially of TLR 2/6 agonists) are incompletely understood. We investigated at a cellular level whether the administration of the pharmacologically improved TLR2/6 agonist S-[2,3-bispalmitoyiloxy-(2R)-propyl]-R-cysteinyl-amido-monomethoxy polyethylene glycol (BPP) conjugated to antigenic peptide (BPP-OVA) could divert an existing Th2 response and influence airway eosinophilia. The effects of BPP-OVA on airway inflammation were assessed in a classic murine sensitization/challenge model and an adoptive transfer model, which involved the adoptive transfer of in vitro differentiated ovalbumin (OVA)-specific Th2 cells. Functional T-cell stimulation by lung dendritic cells (DCs) was determined both in vitro and in vivo, combined with a cytokine secretion analysis. A single mucosal application of BPP-OVA efficiently delivered antigen, led to TLR2-mediated DC activation, and resulted in OVA-specific T-cell proliferation via lung DCs in vivo. In alternative models of allergic airway disease, a single administration of BPP-OVA before OVA challenge (but not BPP alone) significantly reduced airway eosinophilia, most likely through altered antigen-specific T-cell stimulation via DCs. Analyses of adoptively transferred Th2-biased cells after BPP-OVA administration in vivo suggested that BPP-OVA guides antigen-specific Th2 cells to produce significantly higher amounts of IFN-γ upon allergen challenge. In conclusion, our data show for the first time that a single mucosal administration of a TLR 2/6 agonist-allergen conjugate can provoke IFN-γ responses in Th2-biased cells and alleviate allergic airway inflammation.

Novel role for proteinase-activated receptor 2 (PAR2) in membrane trafficking of proteinase-activated receptor 4 (PAR4).

Science.gov (United States)

Cunningham, Margaret R; McIntosh, Kathryn A; Pediani, John D; Robben, Joris; Cooke, Alexandra E; Nilsson, Mary; Gould, Gwyn W; Mundell, Stuart; Milligan, Graeme; Plevin, Robin

2012-05-11

Proteinase-activated receptors 4 (PAR(4)) is a class A G protein-coupled receptor (GPCR) recognized through the ability of serine proteases such as thrombin and trypsin to mediate receptor activation. Due to the irreversible nature of activation, a fresh supply of receptor is required to be mobilized to the cell surface for responsiveness to agonist to be sustained. Unlike other PAR subtypes, the mechanisms regulating receptor trafficking of PAR(4) remain unknown. Here, we report novel features of the intracellular trafficking of PAR(4) to the plasma membrane. PAR(4) was poorly expressed at the plasma membrane and largely retained in the endoplasmic reticulum (ER) in a complex with the COPI protein subunit β-COP1. Analysis of the PAR(4) protein sequence identified an arginine-based (RXR) ER retention sequence located within intracellular loop-2 (R(183)AR → A(183)AA), mutation of which allowed efficient membrane delivery of PAR(4). Interestingly, co-expression with PAR(2) facilitated plasma membrane delivery of PAR(4), an effect produced through disruption of β-COP1 binding and facilitation of interaction with the chaperone protein 14-3-3ζ. Intermolecular FRET studies confirmed heterodimerization between PAR(2) and PAR(4). PAR(2) also enhanced glycosylation of PAR(4) and activation of PAR(4) signaling. Our results identify a novel regulatory role for PAR(2) in the anterograde traffic of PAR(4). PAR(2) was shown to both facilitate and abrogate protein interactions with PAR(4), impacting upon receptor localization and cell signal transduction. This work is likely to impact markedly upon the understanding of the receptor pharmacology of PAR(4) in normal physiology and disease.

Microglia P2Y13 Receptors Prevent Astrocyte Proliferation Mediated by P2Y1 Receptors

Directory of Open Access Journals (Sweden)

Clara Quintas

2018-05-01

Full Text Available Cerebral inflammation is a common feature of several neurodegenerative diseases that requires a fine interplay between astrocytes and microglia to acquire appropriate phenotypes for an efficient response to neuronal damage. During brain inflammation, ATP is massively released into the extracellular medium and converted into ADP. Both nucleotides acting on P2 receptors, modulate astrogliosis through mechanisms involving microglia-astrocytes communication. In previous studies, primary cultures of astrocytes and co-cultures of astrocytes and microglia were used to investigate the influence of microglia on astroglial proliferation induced by ADPβS, a stable ADP analog. In astrocyte cultures, ADPβS increased cell proliferation through activation of P2Y1 and P2Y12 receptors, an effect abolished in co-cultures (of astrocytes with ∼12.5% microglia. The possibility that the loss of the ADPβS-mediated effect could have been caused by a microglia-induced degradation of ADPβS or by a preferential microglial localization of P2Y1 or P2Y12 receptors was excluded. Since ADPβS also activates P2Y13 receptors, the contribution of microglial P2Y13 receptors to prevent the proliferative effect of ADPβS in co-cultures was investigated. The results obtained indicate that P2Y13 receptors are low expressed in astrocytes and mainly expressed in microglia. Furthermore, in co-cultures, ADPβS induced astroglial proliferation in the presence of the selective P2Y13 antagonist MRS 2211 (3 μM and of the selective P2Y12 antagonist AR-C66096 (0.1 μM, suggesting that activation of microglial P2Y12 and P2Y13 receptors may induce the release of messengers that inhibit astroglial proliferation mediated by P2Y1,12 receptors. In this microglia-astrocyte paracrine communication, P2Y12 receptors exert opposite effects in astroglial proliferation as a result of its cellular localization: cooperating in astrocytes with P2Y1 receptors to directly stimulate proliferation and in

Signaling Properties of Chemerin Receptors CMKLR1, GPR1 and CCRL2.

Science.gov (United States)

De Henau, Olivier; Degroot, Gaetan-Nagim; Imbault, Virginie; Robert, Virginie; De Poorter, Cédric; Mcheik, Saria; Galés, Céline; Parmentier, Marc; Springael, Jean-Yves

2016-01-01

Chemerin is a small chemotactic protein originally identified as the natural ligand of CMKLR1. More recently, two other receptors, GPR1 and CCRL2, have been reported to bind chemerin but their functional relevance remains poorly understood. In this study, we compared the binding and signaling properties of the three human chemerin receptors and showed differences in mode of chemerin binding and receptor signaling. Chemerin binds to all three receptors with low nanomolar affinities. However, the contribution of the chemerin C-terminus to binding efficiency varies greatly amongst receptors. By using BRET-based biosensors monitoring the activation of various G proteins, we showed that binding of chemerin and the chemerin 9 nonapeptide (149YFPGQFAFS157) to CMKLR1 activates the three Gαi subtypes (Gαi1, Gαi2 and Gαi3) and the two Gαo isoforms (Gαoa and Gαob) with potencies correlated to binding affinities. In contrast, no significant activation of G proteins was detected upon binding of chemerin to GPR1 or CCRL2. Binding of chemerin and the chemerin 9 peptide also induced the recruitment of β-arrestin1 and 2 to CMKLR1 and GPR1, though to various degree, but not to CCRL2. However, the propensity of chemerin 9 to activate β-arrestins relative to chemerin is higher when bound to GPR1. Finally, we showed that binding of chemerin to CMKLR1 and GPR1 promotes also the internalization of the two receptors and the phosphorylation of ERK1/2 MAP kinases, although with a different efficiency, and that phosphorylation of ERK1/2 requires both Gαi/o and β-arrestin2 activation but not β-arrestin1. Collectively, these data support a model in which each chemerin receptor displays selective signaling properties.

Communication skills to ensure patient satisfaction.

Science.gov (United States)

Shendurnikar, Niranjan; Thakkar, Pareshkumar A

2013-11-01

Every pediatrician would want to satisfy their patients and their parents to sustain good practice, earn name and fame and simultaneously to avoid litigation in this era of consumer protection act. This can be achieved only by use of good communication skills. Today the patients demand time, information and want their questions to be answered. They expect politeness, empathy and human touch from doctors. Time constraints, arrogance, telephone calls, language barriers and cultural insensitivity are the important barriers to good communication. Research has shown that doctor, who undergoes training to acquire good communication skills, can better satisfy his patients. Good communication skill is an art which can be acquired or improved by putting conscious efforts in day to day practice. Such skills should also be incorporated as part of medical teaching curriculum. Asking open ended questions, effective listening, appropriate praise, providing enough information as part of advice and finally checking their understanding, are the key areas of communication during medical interview. During this process pediatrician should ensure to address the parental concerns, should empathize with parents and involve parents in decision making. This will not only ensure satisfaction of parents but also their adherence to the therapy and to the pediatrician.

Closing the Gap GEF Experiences in Global Energy Efficiency

CERN Document Server

Yang, Ming

2013-01-01

Energy efficiency plays and will continue to play an important role in the world to save energy and mitigate greenhouse gas (GHG) emissions. However, little is known on how much additional capital should be invested to ensure using energy efficiently as it should be, and very little is known which sub-areas, technologies, and countries shall achieve maximum greenhouse gas emissions mitigation per dollar of investment in energy efficiency worldwide. Analyzing completed and slowly moving energy efficiency projects by the Global Environment Facility during 1991-2010, Closing the Gap: GEF Experiences in Global Energy Efficiency evaluates impacts of multi-billion-dollar investments in the world energy efficiency. It covers the following areas: 1.       Reviewing the world energy efficiency investment and disclosing the global energy efficiency gap and market barriers that cause the gap; 2.       Leveraging private funds with public funds and other resources in energy efficiency investments; using...

Development of real-time reverse transcription polymerase chain reaction assays to quantify insulin-like growth factor receptor and insulin receptor expression in equine tissue

Directory of Open Access Journals (Sweden)

Stephen B. Hughes

2013-08-01

Full Text Available The insulin-like growth factor system (insulin-like growth factor 1, insulin-like growth factor 2, insulin-like growth factor 1 receptor, insulin-like growth factor 2 receptor and six insulin-like growth factor-binding proteins and insulin are essential to muscle metabolism and most aspects of male and female reproduction. Insulin-like growth factor and insulin play important roles in the regulation of cell growth, differentiation and the maintenance of cell differentiation in mammals. In order to better understand the local factors that regulate equine physiology, such as muscle metabolism and reproduction (e.g., germ cell development and fertilisation, real-time reverse transcription polymerase chain reaction assays for quantification of equine insulin-like growth factor 1 receptor and insulin receptor messenger ribonucleic acid were developed. The assays were sensitive: 192 copies/µLand 891 copies/µL for insulin-like growth factor 1 receptor, messenger ribonucleic acid and insulin receptor respectively (95%limit of detection, and efficient: 1.01 for the insulin-like growth factor 1 receptor assay and 0.95 for the insulin receptor assay. The assays had a broad linear range of detection (seven logs for insulin-like growth factor 1 receptor and six logs for insulin receptor. This allowed for analysis of very small amounts of messenger ribonucleic acid. Low concentrations of both insulin-like growth factor 1 receptor and insulin receptor messenger ribonucleic acid were detected in endometrium, lung and spleen samples, whilst high concentrations were detected in heart, muscle and kidney samples, this was most likely due to the high level of glucose metabolism and glucose utilisation by these tissues. The assays developed for insulin-like growth factor 1 receptor and insulin receptor messenger ribonucleic acid expression have been shown to work on equine tissue and will contribute to the understanding of insulin and insulin-like growth factor 1

Importance of the pharmacological profile of the bound ligand in enrichment on nuclear receptors: toward the use of experimentally validated decoy ligands.

Science.gov (United States)

Lagarde, Nathalie; Zagury, Jean-François; Montes, Matthieu

2014-10-27

The evaluation of virtual ligand screening methods is of major importance to ensure their reliability. Taking into account the agonist/antagonist pharmacological profile should improve the quality of the benchmarking data sets since ligand binding can induce conformational changes in the nuclear receptor structure and such changes may vary according to the agonist/antagonist ligand profile. We indeed found that splitting the agonist and antagonist ligands into two separate data sets for a given nuclear receptor target significantly enhances the quality of the evaluation. The pharmacological profile of the ligand bound in the binding site of the target structure was also found to be an additional critical parameter. We also illustrate that active compound data sets for a given pharmacological activity can be used as a set of experimentally validated decoy ligands for another pharmacological activity to ensure a reliable and challenging evaluation of virtual screening methods.

Energy Efficiency and Importance of Renewable Energy Sources in Latvia

Science.gov (United States)

Skapare, I.; Kreslins, A.

2007-10-01

The main goal of Latvian energy policy is to ensure safe and environmentally friendly long-term energy supply at cost-effective prices, contributing to enhance competitiveness, and to ensure safe energy transit. The Latvian Parliament approved an Energy Efficiency Strategy in 2000. Its objective is to decrease energy consumption per unit of GDP by 25% by 2010. Awareness raising, implementation of standards and economic incentives for self financing are the main instruments to increase energy efficiency, mentioned in the strategy. Latvia, as many other European Union member states, is dependent on the import of primary energy resources. The Latvian Renewable Energy strategy is still under development. The only recent study on RES was developed in the framework of a PHARE program in year 2000: "Renewable energy resource program", where three main objectives for a future RES strategy were proposed: 1. To increase the use of wood waste and low value wood and forest residues. 2. To improve efficiency of combustion technologies and to replace outdated plants. 3. To increase the use of renewables in Combined Heat and Power plants (CHP). Through the Renewable Energy and Energy Efficiency Partnership, partners will develop a set of new shared activities, and coordinate and strengthen existing efforts in this area.

Ensuring Sustainable Development through Urban Planning in Pakistan

Directory of Open Access Journals (Sweden)

Mohammad Qasim

2013-04-01

Full Text Available Urban planning includes land use management and environmental change. It makes arrangement for community facilities and services. Since, sustainable development has been included as a vital end product of all planning goals it also provides for balanced use of land, housing and transportation and better quality of life. Present urban planning in Pakistan is not ensuring sustainable development in Pakistan. This is tested through the case study of master planning in Rawalpindi and its implementation through housing schemes in Rawalpindi, Pakistan. Large portions of provisions of master plans are not implemented. This paper explains how the urban planning will be made enabled to ensure sustainable development in Pakistan. Six numbers of housing schemes and two squatter settlements have been surveyed through questionnaires, secondary data, the opinions of the experts from related fields and site observations. Amenities and social services at far distance, very less green area, Less quantity and bad quality of water, absence of comprehensive solid waste management and sewage disposal system and nontreatment of solid waste, effluent and sewage, prevalent unhygienic conditions and air and water pollution are the existing factors effecting the sustainability. There is a need to revisit the urban planning and a comprehensive Urban and Environment Planning Law at national level and at provincial level is recommended to enable the urban planning to ensure the sustainable development in Pakistan

Ensuring sustainable development through urban planing in pakistan

International Nuclear Information System (INIS)

Qasim, M.; Zaidi, S.S.U.

2013-01-01

Urban planning includes land use management and environmental change. It makes arrangement for community facilities and services. Since, sustainable development has been included as a vital end product of all planning goals it also provides for balanced use of land, housing and transportation and better quality of life. Present urban planning in Pakistan is not ensuring sustainable development in Pakistan. This is tested through the case study of master planning in Rawalpindi and its implementation through housing schemes in Rawalpindi, Pakistan. Large portions of provisions of master plans are not implemented. This paper explains how the urban planning will be made enabled to ensure sustainable development in Pakistan. Six numbers of housing schemes and two squatter settlements have been surveyed through questionnaires, secondary data, the opinions of the experts from related fields and site observations. Amenities and social services at far distance, very less green area, Less quantity and bad quality of water, absence of comprehensive solid waste management and sewage disposal system and non- treatment of solid waste, effluent and sewage, prevalent unhygienic conditions and air and water pollution are the existing factors effecting the sustainability. There is a need to revisit the urban planning and a comprehensive Urban and Environment Planning Law at national level and at provincial level is recommended to enable the urban planning to ensure the sustainable development in Pakistan. (author)

The Experience of Psychological Service of Rosenergoatom in Ensuring the Reliability of the Human Factor

International Nuclear Information System (INIS)

Chernetckaia, E.D.; Belyh, T.

2016-01-01

To ensure the safe and efficient operation of nuclear power plants, since 1982 the laboratories of psycho-physiological support (LPPS) started being established at Russian NPPs. The methodological background for this was later summarised. The LPPS’ activity and professional development of LPPS specialists are currently supported by the scientific methodological centre “Psycho-Physiological Support of Professional Personnel Reliability” (PPSPPR) of Rosatom Central Institute for Continuing Education and Training (ROSATOMCICE& T). The present paper gives the outlines of the main LPPS tasks performed by above mentioned organizations at Russian NPPs: • psycho-physiological examination of candidates and employees (PFE); • psychological and physiological support of workers (PPS); • socio-psychological aspects of safety culture; • psycho-pedagogical support of the educational process.

INTERNAL CONTROLS IN ENSURING GOOD CORPORATE GOVERNANCE IN FINANCIAL INSTITUTIONS

Directory of Open Access Journals (Sweden)

KOSMAS NJANIKE

2011-01-01

Full Text Available This paper assessed factors that influence the internal controls in ensuring good corporate governance in financial institutions in developing economies with special reference to Zimbabwe. The research paper assessed how lack of internal controls affected good corporate governance and aimed to bring out elements of good corporate governance. It emerged that failure to effectively implement internal controls contributed significantly to poor corporate governance. The study discovered that internal control system overrides and the issue of “fact cat” directors also contributed to poor corporate governance. The study recommended that there is need for the board of directors to guarantee an organizational structure that clearly defines management responsibilities, authority and reporting relationships. There is also need to ensure that delegated responsibilities are effectively carried out to ensure compliance with internal controls of the financial institution concerned.

Ensuring Peace and Reconciliation while Holding Leaders ...

African Journals Online (AJOL)

need to be adopted to ensure that both organizations fulfil their mandate to address impunity on the ... international law; international relations and political studies. ...... 'not any other consideration', which was an attempt to assuage any fears that she ... system, which should play into the hands of the AU – in theory. Yet this.

Ensuring food security

Directory of Open Access Journals (Sweden)

Valeriy Valentinovich Patsiorkovskiy

2011-12-01

Full Text Available This paper is devoted to the questions of further development of agricultural and food policy in the Russian Federation. The subject of in-depth consideration is the problem related to ensuring food safety. A critical review and analysis of major regulations in the field of food safety is made, including in the implementation of sanitary and epidemiological surveillance. The necessity of the expansion of measures to improve the statistics of food poisoning is grounded. The basic reasons for the spread of management practices of production and sale of food products that pose a threat to human life are revealed. The factors of unhindered penetration of local markets in the cities and the surrounding countrysides with counterfeiting, smuggling and production of global junk food manufacturers and consumer goods are defined. A systematic view is put on the problems of food production in the private farms, ways to limit direct access to the market of food and food raw materials, which production was not controlled and who have not passed state registration, are suggested. One of these problems is creation of independent industrial structures that link production and sales of small-scale sector goods.

Premium Efficiency Motor Selection and Application Guide – A Handbook for Industry

Energy Technology Data Exchange (ETDEWEB)

Gilbert A. McCoy and John G. Douglass

2014-02-01

This handbook informs new motor purchase decisions by identifying energy and cost savings that can come from replacing motors with premium efficiency units. The handbook provides an overview of current motor use in the industrial sector, including the development of motor efficiency standards, currently available and emerging advanced efficiency motor technologies, and guidance on how to evaluate motor efficiency opportunities. It also several tips on getting the most out of industrial motors, such as how to avoid adverse motor interactions with electronic adjustable speed drives and how to ensure efficiency gains are not lost to undervoltage operation or excessive voltage unbalance.

Cell surface receptors for signal transduction and ligand transport: a design principles study.

Directory of Open Access Journals (Sweden)

Harish Shankaran

2007-06-01

Full Text Available Receptors constitute the interface of cells to their external environment. These molecules bind specific ligands involved in multiple processes, such as signal transduction and nutrient transport. Although a variety of cell surface receptors undergo endocytosis, the systems-level design principles that govern the evolution of receptor trafficking dynamics are far from fully understood. We have constructed a generalized mathematical model of receptor-ligand binding and internalization to understand how receptor internalization dynamics encodes receptor function and regulation. A given signaling or transport receptor system represents a particular implementation of this module with a specific set of kinetic parameters. Parametric analysis of the response of receptor systems to ligand inputs reveals that receptor systems can be characterized as being: i avidity-controlled where the response control depends primarily on the extracellular ligand capture efficiency, ii consumption-controlled where the ability to internalize surface-bound ligand is the primary control parameter, and iii dual-sensitivity where both the avidity and consumption parameters are important. We show that the transferrin and low-density lipoprotein receptors are avidity-controlled, the vitellogenin receptor is consumption-controlled, and the epidermal growth factor receptor is a dual-sensitivity receptor. Significantly, we show that ligand-induced endocytosis is a mechanism to enhance the accuracy of signaling receptors rather than merely serving to attenuate signaling. Our analysis reveals that the location of a receptor system in the avidity-consumption parameter space can be used to understand both its function and its regulation.

Ensuring Effective and Efficient Teaching and Learning Religious ...

African Journals Online (AJOL)

Nekky Umera

enhance the performance of students in selected junior secondary school in ... of students in the subject at secondary schools level and tertiary institution of ... for training teachers in the art and craft of design selection production and use of ... Ogunmilade (1984) stated that Educational Technology can help to rectify the ...

Ensuring Effective and Efficient Teaching and Learning Religious ...

African Journals Online (AJOL)

... the use of photographic series in instruction significantly improved the performance of students in the subject. Secondly if effectively used, it can improve the retentive ability of students and finally, photographic series do not seen to have any statistical effect on the attitude of students towards the subject. African Research ...

ensuring quality control of forensic accounting for efficient

African Journals Online (AJOL)

PROF EKWUEME

or social. “3m” have been identified to be the tool used to effect this crime namely; ... misapplication and misrepresentation of financial information. ... check, accounting control, segregation of duties ... 4) Level of internal control system does not.

METHODOLOGICAL WAY TO ENSURE SELF-DEVELOPMENT OF CHILDREN AND CAREGIVERS IN THE PROCESS OF PRESCHOOL EDUCATION

Directory of Open Access Journals (Sweden)

Marina G. Grushina

2016-01-01

Full Text Available For example, the CRD MUNICIPAL budget preschool educational institution – kinder-center “Baby” the results of realization of noospheric educational technologies adapted to the specifics of children’s age. The methodological possibilities of creative tasks, technology use computer environment, heuristic learning, music education, narrative learning. The analysis of the importance of ensuring the professional competence of teachers. The efficiency bioadequate methods of teaching in practical operation the OED. Through psycho-pedagogical monitoring of creative development of a preschool child a study of the effectiveness of the noosphere theory; generalized educational experience from the standpoint of using environmentally friendly means and methods in the system of training and education. 

Buy Energy-Efficient Products: A Guide for Federal Purchasers and Specifiers

Energy Technology Data Exchange (ETDEWEB)

2016-07-01

In a single year, energy-efficient product purchases could save the federal government almost a half billion dollars worth of energy. By purchasing products that exceed the minimum required efficiency levels, buyers can save the government even more energy and money. Federal employees and contractors must take an active role in ensuring that the government receives products that meet efficiency requirements. This document provides an overview of product purchasing requirements and shows you how to write compliant contracts, find funding, and confirm product compliance.

Somatostatin receptors

DEFF Research Database (Denmark)

Møller, Lars Neisig; Stidsen, Carsten Enggaard; Hartmann, Bolette

2003-01-01

functional units, receptors co-operate. The total receptor apparatus of individual cell types is composed of different-ligand receptors (e.g. SRIF and non-SRIF receptors) and co-expressed receptor subtypes (e.g. sst(2) and sst(5) receptors) in characteristic proportions. In other words, levels of individual......-peptides, receptor agonists and antagonists. Relatively long half lives, as compared to those of the endogenous ligands, have been paramount from the outset. Motivated by theoretical puzzles or the shortcomings of present-day diagnostics and therapy, investigators have also aimed to produce subtype...

Strategies for Ensuring Quality in the Business Education ...

African Journals Online (AJOL)

Strategies for Ensuring Quality in the Business Education Programme of Tertiary Institutions in ... The survey method was employed. One research question guided the study while two null hypotheses were tested at 0.05 degree of significance.

Quality and efficiency in high dimensional Nearest neighbor search

KAUST Repository

Tao, Yufei; Yi, Ke; Sheng, Cheng; Kalnis, Panos

2009-01-01

Nearest neighbor (NN) search in high dimensional space is an important problem in many applications. Ideally, a practical solution (i) should be implementable in a relational database, and (ii) its query cost should grow sub-linearly with the dataset size, regardless of the data and query distributions. Despite the bulk of NN literature, no solution fulfills both requirements, except locality sensitive hashing (LSH). The existing LSH implementations are either rigorous or adhoc. Rigorous-LSH ensures good quality of query results, but requires expensive space and query cost. Although adhoc-LSH is more efficient, it abandons quality control, i.e., the neighbor it outputs can be arbitrarily bad. As a result, currently no method is able to ensure both quality and efficiency simultaneously in practice. Motivated by this, we propose a new access method called the locality sensitive B-tree (LSB-tree) that enables fast highdimensional NN search with excellent quality. The combination of several LSB-trees leads to a structure called the LSB-forest that ensures the same result quality as rigorous-LSH, but reduces its space and query cost dramatically. The LSB-forest also outperforms adhoc-LSH, even though the latter has no quality guarantee. Besides its appealing theoretical properties, the LSB-tree itself also serves as an effective index that consumes linear space, and supports efficient updates. Our extensive experiments confirm that the LSB-tree is faster than (i) the state of the art of exact NN search by two orders of magnitude, and (ii) the best (linear-space) method of approximate retrieval by an order of magnitude, and at the same time, returns neighbors with much better quality. © 2009 ACM.

Molecular docking study of Papaver alkaloids to some alkaloid receptors

Directory of Open Access Journals (Sweden)

A. Nofallah

2017-11-01

Full Text Available Background and objectives: More than 40 different alkaloids have been obtained from opium the most important of which are morphine, codeine, papaverine, noscapine and tabaine. Opioid alkaloids produce analgesia by affecting areas of the brain that have peptides with pharmacological pseudo-opioid properties. These alkaloids show important effects on some intracellular peptides like mu, delta, and kappa receptors. Therefore, studying the effects of these alkaloids on different receptors is essential. Methods: Molecular docking is a well-known method in exploring the protein-ligand interactions. In this research, five important alkaloids were docked to crystal structure of human mu opioid receptor (4DKL, human delta opioid receptor (4EJ4 and human kappa opioid receptor (4DJH which were retrieved from protein databank. The 3D-structures of alkaloids were drawn by chembiooffice2010 and minimized with hyperchem package and submitted to molecular docking utilizing autodock-vina. Flexibility of the proteins was considered. The docking studies were performed to compare the affinity of these five alkaloids to the mentioned receptors. Results: We computationally docked each alkaloid compound onto each receptor structure and estimated their binding affinity based on dock scores. Dock score is a criteria including binding energy which utilized here for prediction and comparison of the binding affinities. Binding interactions of the docked alkaloids in receptor pockets were also visually inspected and compared. Conclusion: In this approach, using docking study as a computational method provided a valuable insight of opioid receptor pocket structures which would be essential to design more efficient drugs in pain managements and addiction treatments.

Ensuring Academic Standards in US Higher Education

Science.gov (United States)

Dill, David D.

2014-01-01

The most recent research on college-student learning in the US by respected scholars such as Richard Arum, Josipa Roksa, and Ernest Pascarella suggests that the nation's means of ensuring academic standards in US colleges and universities are not working effectively. Like US K-12 education and health care, the US higher education system is…

Energy Efficient Design for Two-Way AF Relay Networks

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Yong Li

2014-01-01

Full Text Available Conventional designs on two-way relay networks mainly focus on the spectral efficiency (SE rather than energy efficiency (EE. In this paper, we consider a system where two source nodes communicate with each other via an amplify-and-forward (AF relay node and study the power allocation schemes to maximize EE while ensuring a certain data rate. We propose an optimal energy-efficient power allocation algorithm based on iterative search technique. In addition, a closed-form suboptimal solution is derived with reduced complexity and negligible performance degradation. Numerical results show that the proposed schemes can achieve considerable EE improvement compared with conventional designs.

ENSURING THE SAFETY OF ROAD TRANSPORTATION OF GOODS

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Liudmila Nikolaevna Andronikova

2017-05-01

Full Text Available The article investigates Russian and foreign regulatory documents, governing the issues of cargo securing in road transport, and sets out recommendations to ensure the safety of road transportation of goods by means of their attachment.

A multipronged approach to ensuring food security | IDRC ...

International Development Research Centre (IDRC) Digital Library (Canada)

2011-02-01

Feb 1, 2011 ... ... nations committed themselves to ensuring an enabling environment and ... to eradicate poverty and guarantee access to sufficient, safe food to all. They also agreed to promote a fair world trade system, and to work to ...

Large-scale overproduction, functional purification and ligand affinities of the His-tagged human histamine H1 receptor.

NARCIS (Netherlands)

Ratnala, V.R.; Swarts, H.G.P.; Oostrum, J. van; Leurs, R.; Groot, H.J.M. de; Bakker, R.; Grip, W.J. de

2004-01-01

This report describes an efficient strategy for amplified functional purification of the human H1 receptor after heterologous expression in Sf9 cells. The cDNA encoding a C-terminally histidine-tagged (10xHis) human histamine H1 receptor was used to generate recombinant baculovirus in a Spodoptera

Class I Cytokine Receptors: Structure and function in the Membrane

DEFF Research Database (Denmark)

Bugge, Katrine Østergaard

bilayer via structural characterizations of TMD representatives. To enable structural studies of these domains, an organic-extraction based strategy for efficient production of isotope-labeled TMDs with or without short intrinsically disordered regions was developed. This strategy successfully provided...... of these challenging domains. Supplemented by a review of the current collection of TMD structures from single-pass transmembrane receptors, the thesis as a whole provides important insights on the structure and function in the membrane as well as highlight the open questions to be addressed in the years to come.......Class I cytokine receptors are involved in important biological functions of both physiological and pathological nature in mammals. However, the molecular details of the cross-membrane signal transduction through these receptors remain obscure. One of the major reasons for this is the lack...

Application of sorption heat pumps for increasing of new power sources efficiency

Science.gov (United States)

Vasiliev, L.; Filatova, O.; Tsitovich, A.

2010-07-01

In the 21st century the way to increase the efficiency of new sources of energy is directly related with extended exploration of renewable energy. This modern tendency ensures the fuel economy needs to be realized with nature protection. The increasing of new power sources efficiency (cogeneration, trigeneration systems, fuel cells, photovoltaic systems) can be performed by application of solid sorption heat pumps, regrigerators, heat and cold accumulators, heat transformers, natural gas and hydrogen storage systems and efficient heat exchangers.

High-efficiency photovoltaic technology including thermoelectric generation

Science.gov (United States)

Fisac, Miguel; Villasevil, Francesc X.; López, Antonio M.

2014-04-01

Nowadays, photovoltaic solar energy is a clean and reliable source for producing electric power. Most photovoltaic systems have been designed and built up for use in applications with low power requirements. The efficiency of solar cells is quite low, obtaining best results in monocrystalline silicon structures, with an efficiency of about 18%. When temperature rises, photovoltaic cell efficiency decreases, given that the short-circuit current is slightly increased, and the open-circuit voltage, fill factor and power output are reduced. To ensure that this does not affect performance, this paper describes how to interconnect photovoltaic and thermoelectric technology into a single structure. The temperature gradient in the solar panel is used to supply thermoelectric cells, which generate electricity, achieving a positive contribution to the total balance of the complete system.

Lipids Derived from Virulent Francisella tularensis Broadly Inhibit Pulmonary Inflammation via Toll-Like Receptor 2 and Peroxisome Proliferator-Activated Receptor α

Science.gov (United States)

Crane, Deborah D.; Ireland, Robin; Alinger, Joshua B.; Small, Pamela

2013-01-01

Francisella tularensis is a Gram-negative facultative intracellular pathogen that causes an acute lethal respiratory disease in humans. The heightened virulence of the pathogen is linked to its unique ability to inhibit Toll-like receptor (TLR)-mediated inflammatory responses. The bacterial component and mechanism of this inhibition are unknown. Here we show that lipids isolated from virulent but not attenuated strains of F. tularensis are not detected by host cells, inhibit production of proinflammatory cytokines by primary macrophages in response to known TLR ligands, and suppress neutrophil recruitment in vivo. We further show that lipid-mediated inhibition of inflammation is dependent on TLR2, MyD88, and the nuclear hormone and fatty acid receptor peroxisome proliferator-activated receptor α (PPARα). Pathogen lipid-mediated interference with inflammatory responses through the engagement of TLR2 and PPARα represents a novel manipulation of host signaling pathways consistent with the ability of highly virulent F. tularensis to efficiently evade host immune responses. PMID:23925884

MicroRNA-27a decreases the level and efficiency of the LDL receptor and contributes to the dysregulation of cholesterol homeostasis.

Science.gov (United States)

Alvarez, M Lucrecia; Khosroheidari, Mahdieh; Eddy, Elena; Done, Stefania C

2015-10-01

A strong risk factor for atherosclerosis- the leading cause of heart attacks and strokes- is the elevation of low-density lipoprotein cholesterol (LDL-C) in blood. The LDL receptor (LDLR) is the primary pathway for LDL-C removal from circulation, and their levels are increased by statins -the main treatment for high blood LDL-C. However, statins have low efficiency because they also increase PCSK9 which targets LDLR for degradation. Since microRNAs have recently emerged as key regulators of cholesterol homeostasis, our aim was to identify potential microRNA-based therapeutics to decrease blood LDL-C and prevent atherosclerosis. We over expressed and knocked down miR-27a in HepG2 cells to assess its effect on the expression of key players in the LDLR pathway using PCR Arrays, Elisas, and Western blots. We found that miR-27a decreases LDLR levels by 40% not only through a direct binding to its 3' untranslated region but also indirectly by inducing a 3-fold increase in PCSK9, which enhances LDLR degradation. Interestingly, miR-27a also directly decreases LRP6 and LDLRAP1, two other key players in the LDLR pathway that are required for efficient endocytosis of the LDLR-LDL-C complex in the liver. The inhibition of miR-27a using lock nucleic acids induced a 70% increase in LDLR levels and, therefore, it would be a more efficient treatment for hypercholesterolemia because of its desirable effects not only on LDLR but also on PCSK9. The results presented here provide evidence supporting the potential of miR-27a as a novel therapeutic target for the prevention of atherosclerosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Energy Efficiency Roadmap for Uganda, Making Energy Efficiency Count. Executive Summary

Energy Technology Data Exchange (ETDEWEB)

de la Rue du Can, Stephane; Pudleiner, David; Jones, David; Khan, Aleisha

2017-06-15

Like many countries in Sub-Saharan Africa, Uganda has focused its energy sector investments largely on increasing energy access by increasing energy supply. The links between energy efficiency and energy access, the importance of energy efficiency in new energy supply, and the multiple benefits of energy efficiency for the level and quality of energy available, have been largely overlooked. Implementing energy efficiency in parallel with expanding both the electricity grid and new clean energy generation reduces electricity demand and helps optimize the power supply so that it can serve more customers reliably at minimum cost. Ensuring efficient appliances are incorporated into energy access efforts provides improved energy services to customers. Energy efficiency is an important contributor to access to modern energy. This Energy Efficiency Roadmap for Uganda (Roadmap) is a response to the important role that electrical energy efficiency can play in meeting Uganda’s energy goals. Power Africa and the United Nations Sustainable Energy for All (SEforALL) initiatives collaborated with more than 24 stakeholders in Uganda to develop this document. The document estimates that if the most efficient technologies on the market were adopted, 2,224 gigawatt hours could be saved in 2030 across all sectors, representing 31% of the projected load. This translates into 341 megawatts of peak demand reductions, energy access to an additional 6 million rural customers and reduction of carbon dioxide emissions by 10.6 million tonnes in 2030. The Roadmap also finds that 91% of this technical potential is cost-effective, and 47% is achievable under conservative assumptions. The Roadmap prioritizes recommendations for implementing energy efficiency and maximizing benefits to meet the goals and priorities established in Uganda’s 2015 SEforALL Action Agenda. One important step is to create and increase demand for efficiency through long-term enabling policies and financial incentives

Smart LED allocation scheme for efficient multiuser visible light communication networks.

Science.gov (United States)

Sewaiwar, Atul; Tiwari, Samrat Vikramaditya; Chung, Yeon Ho

2015-05-18

In a multiuser bidirectional visible light communication (VLC), a large number of LEDs or an LED array needs to be allocated in an efficient manner to ensure sustainable data rate and link quality. Moreover, in order to support an increasing or decreasing number of users in the network, the LED allocation is required to be performed dynamically. In this paper, a novel smart LED allocation scheme for efficient multiuser VLC networks is presented. The proposed scheme allocates RGB LEDs to multiple users in a dynamic and efficient fashion, while satisfying illumination requirements in an indoor environment. The smart LED array comprised of RGB LEDs is divided into sectors according to the location of the users. The allocated sectors then provide optical power concentration toward the users for efficient and reliable data transmission. An algorithm for the dynamic allocation of the LEDs is also presented. To verify its effective resource allocation feature of the proposed scheme, simulations were performed. It is found that the proposed smart LED allocation scheme provides the effect of optical beamforming toward individual users, thereby increasing the collective power concentration of the optical signals on the desirable users and resulting in significantly increased data rate, while ensuring sufficient illumination in a multiuser VLC environment.

Energy Efficiency Policy and Carbon Pricing

Energy Technology Data Exchange (ETDEWEB)

NONE

2011-07-01

The main message of this paper is that while carbon pricing is a prerequisite for least-cost carbon mitigation strategies, carbon pricing is not enough to overcome all the barriers to cost-effective energy efficiency actions. Energy efficiency policy should be designed carefully for each sector to ensure optimal outcomes for a combination of economic, social and climate change goals. This paper aims to examine the justification for specific energy efficiency policies in economies with carbon pricing in place. The paper begins with an inventory of existing market failures that attempt to explain the limited uptake of energy efficiency. These market failures are investigated to see which can be overcome by carbon pricing in two subsectors -- electricity use in residential appliances and heating energy use in buildings. This analysis finds that carbon pricing addresses energy efficiency market failures such as externalities and imperfect energy markets. However, several market and behavioural failures in the two subsectors are identified that appear not to be addressed by carbon pricing. These include: imperfect information; principal-agent problems; and behavioural failures. In this analysis, the policies that address these market failures are identified as complementary to carbon pricing and their level of interaction with carbon pricing policies is relatively positive. These policies should be implemented when they can improve energy efficiency effectively and efficiently (and achieve other national goals such as improving socio-economic efficiency).

Insulin receptors

International Nuclear Information System (INIS)

Kahn, C.R.; Harrison, L.C.

1988-01-01

This book contains the proceedings on insulin receptors. Part A: Methods for the study of structure and function. Topics covered include: Method for purification and labeling of insulin receptors, the insulin receptor kinase, and insulin receptors on special tissues

Strategies for ensuring quality data from Indian investigational sites

Directory of Open Access Journals (Sweden)

Antal K Hajos

2011-01-01

Full Text Available The topic of ensuring quality and compliance is and must be a top priority in the conduct of clinical trials, as warranted by regulatory guidelines as well as the inherent responsibility of the professionals conducting such research. Fast-growing emerging clinical geographies such as India demand special attention due to rapid growth and associated factors that may put study quality at risk. In this paper, we used the basic principle of PDCA (Plan, Do, Check, and Adjust to structure the processes of a clinical trial from protocol to final analysis in order to highlight the interactive nature of involved people and processes required to ensure quality of data and site functioning.

Strategy for monitoring and ensuring safe operation of Russian gas transportation systems

Directory of Open Access Journals (Sweden)

Dudin Sergey

2017-01-01

Full Text Available The authors examined the legislative framework of the Russian Federation operating in the field of industrial safety, and described how to obtain a license to operate hazardous production facilities. The paper demonstrates that the importance should be given to the quality and completeness of the background information, as well as the choice of inspection strategy in evaluating the technical condition of the line section of main gas pipelines. As a part of a package of measures to ensure industrial safety and technical reliability of existing gas pipelines it is proposed to carry out conditioning of their line sections. The paper describes general requirements for pipeline inspection, which include: detection efficiency of dangerous damages and major leaks, maximum accuracy of detection of the defect location, continuity of monitoring throughout the entire range of operation modes of the pipeline, cost recovery at the stages of development and operation of control systems, forecasting the state of the pipeline and the effects of accidents. In practice, these parameters have the prevailing significance.

Cas4-Dependent Prespacer Processing Ensures High-Fidelity Programming of CRISPR Arrays.

Science.gov (United States)

Lee, Hayun; Zhou, Yi; Taylor, David W; Sashital, Dipali G

2018-04-05

CRISPR-Cas immune systems integrate short segments of foreign DNA as spacers into the host CRISPR locus to provide molecular memory of infection. Cas4 proteins are widespread in CRISPR-Cas systems and are thought to participate in spacer acquisition, although their exact function remains unknown. Here we show that Bacillus halodurans type I-C Cas4 is required for efficient prespacer processing prior to Cas1-Cas2-mediated integration. Cas4 interacts tightly with the Cas1 integrase, forming a heterohexameric complex containing two Cas1 dimers and two Cas4 subunits. In the presence of Cas1 and Cas2, Cas4 processes double-stranded substrates with long 3' overhangs through site-specific endonucleolytic cleavage. Cas4 recognizes PAM sequences within the prespacer and prevents integration of unprocessed prespacers, ensuring that only functional spacers will be integrated into the CRISPR array. Our results reveal the critical role of Cas4 in maintaining fidelity during CRISPR adaptation, providing a structural and mechanistic model for prespacer processing and integration. Copyright © 2018 Elsevier Inc. All rights reserved.

Quality and Efficiency Improvement Tools for Every Radiologist.

Science.gov (United States)

Kudla, Alexei U; Brook, Olga R

2018-03-20

In an era of value-based medicine, data-driven quality improvement is more important than ever to ensure safe and efficient imaging services. Familiarity with high-value tools enables all radiologists to successfully engage in quality and efficiency improvement. In this article, we review the model for improvement, strategies for measurement, and common practical tools with real-life examples that include Run chart, Control chart (Shewhart chart), Fishbone (Cause-and-Effect or Ishikawa) diagram, Pareto chart, 5 Whys, and Root Cause Analysis. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Development of the innovative food industry in the conditions of ensuring food security

OpenAIRE

Berdiev S.

2017-01-01

The purpose of this article is to ensure the safety of food and through the development of innovative food industry and learning to increase the production of food. Work to ensure food security of the Republic of Uzbekistan has its own characteristics and analysis of trends and problems identified in this area. As well as ensuring the safety of food and food industry offer based on the priority directions of scientific and practical recommendations developed.

Reviews on the efficient nuclear material accountability at KAERI

International Nuclear Information System (INIS)

Kim, Hyun Sook; Ko, Han Suk; Lee, Seung Ho; Park, Ho Joon; Lee, Byung Doo

2011-01-01

KAERI(Korea Atomic Energy Research Institute) is constantly trying to efficiently implement safeguards in order to ensure international transparency and the credibility of KAERI safeguards. In its continuing efforts to implement safeguards efficiently, KAERI has developed KASIS(KAERI Safeguards Information Treatment System) and has linked KASIS with the RF ID system and HANARO fuel fabrication facility system. This paper describes the status of enhanced nuclear material accountancy through the development of KASIS at KAERI. The plans to more effectively implement nuclear material accountancy at KAERI are also reviewed

METHODS FOR RECOMBINANT EXPRESSION AND FUNCTIONAL CHARACTERIZATION OF HUMAN CANNABINOID RECEPTOR CB2

Directory of Open Access Journals (Sweden)

Alexei A. Yeliseev

2013-03-01

Full Text Available Cannabinoid receptor CB2 is a seven transmembrane-domain integral membrane protein that belongs to a large superfamily of G protein-coupled receptors (GPCR. CB2 is a part of the endocannabinoid system that plays vital role in regulation of immune response, inflammation, pain sensitivity, obesity and other physiological responses. Information about the structure and mechanisms of functioning of this receptor in cell membranes is essential for the rational development of specific pharmaceuticals. Here we review the methodology for recombinant expression, purification, stabilization and biochemical characterization of CB2 suitable for preparation of multi-milligram quantities of functionally active receptor. The biotechnological protocols include expression of the recombinant CB2 in E. coli cells as a fusion with the maltose binding protein, stabilization with a high affinity ligand and a derivative of cholesterol in detergent micelles, efficient purification by tandem affinity chromatography, and reconstitution of the receptor into lipid bilayers. The purified recombinant CB2 receptor is amenable to functional and structural studies including nuclear magnetic resonance spectroscopy and a wide range of biochemical and biophysical techniques.

Communication equipment radiation resistance ensurance

International Nuclear Information System (INIS)

Myrova, L.O.; Chelizhenko, A.Z.

1983-01-01

A review of works on radiation resistance of electronic equipment (epsilon epsilon) for 15 years is presented. The effect of ionizing radiation appearing as a result of nuclear explosions in nuclear facilities and in outerspace on epsilon epsilon has been considered. Types of radiation effects in epsilon epsilon, radiation effect on semiconductor devices and integrated circUits, types of epsilon epsilon failures, as well as the procass of radiation-resistant epsilon epsilon designing and selection of its main parameters have been described. The methods of epsilon epsilon flowsheet optimization, application of mathematical simulation and peculiarities of ensurance of epsilon epsilon radiation resistance of communication systems are considered. Peculiarities of designing of radiation-resistant quartz generators, secondary power supply sources and amplifiers are discussed

The Role of Communication in Ensuring Sustained Behavior Change

Science.gov (United States)

Webinar series on communications strategies and methods addresses how communications tools can be used throughout the implementation of climate and clean energy programs to achieve behavior change and ensure sustained.

Zebrafish GDNF and its co-receptor GFRα1 activate the human RET receptor and promote the survival of dopaminergic neurons in vitro.

Directory of Open Access Journals (Sweden)

Tuulia Saarenpää

Full Text Available Glial cell line-derived neurotrophic factor (GDNF is a ligand that activates, through co-receptor GDNF family receptor alpha-1 (GFRα1 and receptor tyrosine kinase "RET", several signaling pathways crucial in the development and sustainment of multiple neuronal populations. We decided to study whether non-mammalian orthologs of these three proteins have conserved their function: can they activate the human counterparts? Using the baculovirus expression system, we expressed and purified Danio rerio RET, and its binding partners GFRα1 and GDNF, and Drosophila melanogaster RET and two isoforms of co-receptor GDNF receptor-like. Our results report high-level insect cell expression of post-translationally modified and dimerized zebrafish RET and its binding partners. We also found that zebrafish GFRα1 and GDNF are comparably active as mammalian cell-produced ones. We also report the first measurements of the affinity of the complex to RET in solution: at least for zebrafish, the Kd for GFRα1-GDNF binding RET is 5.9 μM. Surprisingly, we also found that zebrafish GDNF as well as zebrafish GFRα1 robustly activated human RET signaling and promoted the survival of cultured mouse dopaminergic neurons with comparable efficiency to mammalian GDNF, unlike E. coli-produced human proteins. These results contradict previous studies suggesting that mammalian GFRα1 and GDNF cannot bind and activate non-mammalian RET and vice versa.

Stabilization of functional recombinant cannabinoid receptor CB(2 in detergent micelles and lipid bilayers.

Directory of Open Access Journals (Sweden)

Krishna Vukoti

Full Text Available Elucidation of the molecular mechanisms of activation of G protein-coupled receptors (GPCRs is among the most challenging tasks for modern membrane biology. For studies by high resolution analytical methods, these integral membrane receptors have to be expressed in large quantities, solubilized from cell membranes and purified in detergent micelles, which may result in a severe destabilization and a loss of function. Here, we report insights into differential effects of detergents, lipids and cannabinoid ligands on stability of the recombinant cannabinoid receptor CB(2, and provide guidelines for preparation and handling of the fully functional receptor suitable for a wide array of downstream applications. While we previously described the expression in Escherichia coli, purification and liposome-reconstitution of multi-milligram quantities of CB(2, here we report an efficient stabilization of the recombinant receptor in micelles - crucial for functional and structural characterization. The effects of detergents, lipids and specific ligands on structural stability of CB(2 were assessed by studying activation of G proteins by the purified receptor reconstituted into liposomes. Functional structure of the ligand binding pocket of the receptor was confirmed by binding of (2H-labeled ligand measured by solid-state NMR. We demonstrate that a concerted action of an anionic cholesterol derivative, cholesteryl hemisuccinate (CHS and high affinity cannabinoid ligands CP-55,940 or SR-144,528 are required for efficient stabilization of the functional fold of CB(2 in dodecyl maltoside (DDM/CHAPS detergent solutions. Similar to CHS, the negatively charged phospholipids with the serine headgroup (PS exerted significant stabilizing effects in micelles while uncharged phospholipids were not effective. The purified CB(2 reconstituted into lipid bilayers retained functionality for up to several weeks enabling high resolution structural studies of this GPCR at

Energy Efficiency and Air Quality Repairs at Lyonsdale Biomass

Energy Technology Data Exchange (ETDEWEB)

Brower, Michael R; Morrison, James A; Spomer, Eric; Thimot, Carol A

2012-07-31

This project enabled Lyonsdale Biomass, LLC to effect analyses, repairs and upgrades for its biomass cogeneration facility located in Lewis County, New York and close by the Adirondack Park to reduce air emissions by improving combustion technique and through the overall reduction of biomass throughput by increasing the system's thermodynamic efficiency for its steam-electrical generating cycle. Project outcomes result in significant local, New York State, Northeast U.S. and national benefits including improved renewable energy operational surety, enhanced renewable energy efficiency and more freedom from foreign fossil fuel source dependence. Specifically, the reliability of the Lyonsdale Biomass 20MWe woody biomass combined-heat and power (CHP) was and is now directly enhanced. The New York State and Lewis County benefits are equally substantial since the facility sustains 26 full-time equivalency (FTE) jobs at the facility and as many as 125 FTE jobs in the biomass logistics supply chain. Additionally, the project sustains essential local and state payment in lieu of taxes revenues. This project helps meet several USDOE milestones and contributes directly to the following sustainability goals:  Climate: Reduces greenhouse gas emissions associated with bio-power production, conversion and use, in comparison to fossil fuels. Efficiency and Productivity: Enhances efficient use of renewable resources and maximizes conversion efficiency and productivity. Profitability: Lowers production costs. Rural Development: Enhances economic welfare and rural development through job creation and income generation. Standards: Develop standards and corresponding metrics for ensuring sustainable biopower production. Energy Diversification and Security: Reduces dependence on foreign oil and increases energy supply diversity. Net Energy Balance: Ensures positive net energy balance for all alternatives to fossil fuels.

Quantification of the number of EP3 receptors on a living CHO cell surface by the AFM

International Nuclear Information System (INIS)

Kim, Hyonchol; Arakawa, Hideo; Hatae, Noriyuki; Sugimoto, Yukihiko; Matsumoto, Osamu; Osada, Toshiya; Ichikawa, Atsushi; Ikai, Atsushi

2006-01-01

The distribution of EP3 receptors on a living cell surface was quantitatively studied by atomic force microscopy (AFM). Green fluorescent protein (GFP) was introduced to the extracellular region of the EP3 receptor on a CHO cell. A microbead was used as a probe to ensure certain contact area, whose surface was coated with anti-GFP antibody. The interactions between the antibodies and GFP molecules on the cell surface were recorded to observe the distribution of the receptors. The result indicated that EP3 receptors were distributed on the CHO cell surface not uniformly but in small patches coincident with immunohistochemical observation. Repeated measurements on the same area of cell surface gave confirmation that it was unlikely that the receptors were extracted from the cell membrane during the experiments. The measurement of single molecular interaction between GFP and the anti-GFP antibody was succeeded on the cell surface using compression-free force spectroscopy. The value of separation work required to break a single molecular pair was estimated to be about 1.5x10 -18 J. The number of EP3 receptor on the CHO cell surface was estimated using this value to be about 1x10 4 under the assumption that the area of the cell surface was about 5000 μm 2 . These results indicated that the number of receptors on a living cell surface could be quantified through the force measurement by the AFM

The efficiency of direct torque control for electric vehicle behavior improvement

Directory of Open Access Journals (Sweden)

Gasbaoui Brahim

2011-01-01

Full Text Available Nowadays the electric vehicle motorization control takes a great interest of industrials for commercialized electric vehicles. This paper is one example of the proposed control methods that ensure both safety and stability the electric vehicle by the means of Direct Torque Control (DTC. For motion of the vehicle the electric drive consists of four wheels: two front ones for steering and two rear ones for propulsion equipped with two induction motors, due to their lightweight simplicity and high performance. Acceleration and steering are ensured by the electronic differential, permitting safe and reliable steering at any curve. The direct torque control ensures efficiently controlled vehicle. Electric vehicle direct torque control is simulated in MATLAB SIMULINK environment. Electric vehicle (EV demonstrated satisfactory results in all type of roads constraints: straight, ramp, downhill and bends.

Foot-and-Mouth Disease Virus Receptors: Comparison of Bovine αV Integrin Utilization by Type A and O Viruses

Science.gov (United States)

Duque, Hernando; Baxt, Barry

2003-01-01

Three members of the αV integrin family of cellular receptors, αVβ1, αVβ3, and αVβ6, have been identified as receptors for foot-and-mouth disease virus (FMDV) in vitro. The virus interacts with these receptors via a highly conserved arginine-glycine-aspartic acid (RGD) amino acid sequence motif located within the βG-βH (G-H) loop of VP1. Other αV integrins, as well as several other integrins, recognize and bind to RGD motifs on their natural ligands and also may be candidate receptors for FMDV. To analyze the roles of the αV integrins from a susceptible species as viral receptors, we molecularly cloned the bovine β1, β5, and β6 integrin subunits. Using these subunits, along with previously cloned bovine αV and β3 subunits, in a transient expression assay system, we compared the efficiencies of infection mediated by αVβ1, αVβ3, αVβ5, and αVβ6 among three strains of FMDV serotype A and two strains of serotype O. While all the viruses could infect cells expressing these integrins, they exhibited different efficiencies of integrin utilization. All the type A viruses used αVβ3 and αVβ6 with relatively high efficiency, while only one virus utilized αVβ1 with moderate efficiency. In contrast, both type O viruses utilized αVβ6 and αVβ1 with higher efficiency than αVβ3. Only low levels of viral replication were detected in αVβ5-expressing cells infected with either serotype. Experiments in which the ligand-binding domains among the β subunits were exchanged indicated that this region of the integrin subunit appears to contribute to the differences in integrin utilizations among strains. In contrast, the G-H loops of the different viruses do not appear to be involved in this phenomenon. Thus, the ability of the virus to utilize multiple integrins in vitro may be a reflection of the use of multiple receptors during the course of infection within the susceptible host. PMID:12551988

Molecular, pharmacological, and signaling properties of octopamine receptors from honeybee (Apis mellifera) brain.

Science.gov (United States)

Balfanz, Sabine; Jordan, Nadine; Langenstück, Teresa; Breuer, Johanna; Bergmeier, Vera; Baumann, Arnd

2014-04-01

G protein-coupled receptors are important regulators of cellular signaling processes. Within the large family of rhodopsin-like receptors, those binding to biogenic amines form a discrete subgroup. Activation of biogenic amine receptors leads to transient changes of intracellular Ca²⁺-([Ca²⁺](i)) or 3',5'-cyclic adenosine monophosphate ([cAMP](i)) concentrations. Both second messengers modulate cellular signaling processes and thereby contribute to long-lasting behavioral effects in an organism. In vivo pharmacology has helped to reveal the functional effects of different biogenic amines in honeybees. The phenolamine octopamine is an important modulator of behavior. Binding of octopamine to its receptors causes elevation of [Ca²⁺](i) or [cAMP](i). To date, only one honeybee octopamine receptor that induces Ca²⁺ signals has been molecularly and pharmacologically characterized. Here, we examined the pharmacological properties of four additional honeybee octopamine receptors. When heterologously expressed, all receptors induced cAMP production after binding to octopamine with EC₅₀(s) in the nanomolar range. Receptor activity was most efficiently blocked by mianserin, a substance with antidepressant activity in vertebrates. The rank order of inhibitory potency for potential receptor antagonists was very similar on all four honeybee receptors with mianserin > cyproheptadine > metoclopramide > chlorpromazine > phentolamine. The subroot of octopamine receptors activating adenylyl cyclases is the largest that has so far been characterized in arthropods, and it should now be possible to unravel the contribution of individual receptors to the physiology and behavior of honeybees. © 2013 International Society for Neurochemistry.

Exploring the scope of community-based rehabilitation in ensuring ...

African Journals Online (AJOL)

... the scope of community-based rehabilitation in ensuring the holistic ... Rehabilitation is defined as the process of combined ... psychological measures for enabling individuals to at- ... inclusion, meeting basic needs and facilitating access to.

Entry of Francisella tularensis into Murine B Cells: The Role of B Cell Receptors and Complement Receptors.

Directory of Open Access Journals (Sweden)

Lenka Plzakova

Full Text Available Francisella tularensis, the etiological agent of tularemia, is an intracellular pathogen that dominantly infects and proliferates inside phagocytic cells but can be seen also in non-phagocytic cells, including B cells. Although protective immunity is known to be almost exclusively associated with the type 1 pathway of cellular immunity, a significant role of B cells in immune responses already has been demonstrated. Whether their role is associated with antibody-dependent or antibody-independent B cell functions is not yet fully understood. The character of early events during B cell-pathogen interaction may determine the type of B cell response regulating the induction of adaptive immunity. We used fluorescence microscopy and flow cytometry to identify the basic requirements for the entry of F. tularensis into B cells within in vivo and in vitro infection models. Here, we present data showing that Francisella tularensis subsp. holarctica strain LVS significantly infects individual subsets of murine peritoneal B cells early after infection. Depending on a given B cell subset, uptake of Francisella into B cells is mediated by B cell receptors (BCRs with or without complement receptor CR1/2. However, F. tularensis strain FSC200 ΔiglC and ΔftdsbA deletion mutants are defective in the ability to enter B cells. Once internalized into B cells, F. tularensis LVS intracellular trafficking occurs along the endosomal pathway, albeit without significant multiplication. The results strongly suggest that BCRs alone within the B-1a subset can ensure the internalization process while the BCRs on B-1b and B-2 cells need co-signaling from the co receptor containing CR1/2 to initiate F. tularensis engulfment. In this case, fluidity of the surface cell membrane is a prerequisite for the bacteria's internalization. The results substantially underline the functional heterogeneity of B cell subsets in relation to F. tularensis.

Functional role of the extracellular N-terminal domain of neuropeptide Y subfamily receptors in membrane integration and agonist-stimulated internalization.

Science.gov (United States)

Lindner, Diana; Walther, Cornelia; Tennemann, Anja; Beck-Sickinger, Annette G

2009-01-01

The N terminus is the most variable element in G protein-coupled receptors (GPCRs), ranging from seven residues up to approximately 5900 residues. For family B and C GPCRs it is described that at least part of the ligand binding site is located within the N terminus. Here we investigated the role of the N terminus in the neuropeptide Y receptor family, which belongs to the class A of GPCRs. We cloned differentially truncated Y receptor mutants, in which the N terminus was partially or completely deleted. We found, that eight amino acids are sufficient for full ligand binding and signal transduction activity. Interestingly, we could show that no specific amino acids but rather the extension of the first transmembrane helix by any residues is sufficient for receptor activity but also for membrane integration in case of the hY(1) and the hY(4) receptors. In contrast, the complete deletion of the N terminus in the hY(2) receptors resulted in a mutant that is fully integrated in the membrane but does not bind the ligand very well and internalizes much slower compared to the wild type receptor. Interestingly, also these effects could be reverted by any N-terminal extension. Accordingly, the most important function of the N termini seems to be the stabilization of the first transmembrane helix to ensure the correct receptor structure, which obviously is essential for ligand binding, integration into the cell membrane and receptor internalization.

Ensuring Equal Access to High-Quality Education. Revised

Science.gov (United States)

Office for Civil Rights, US Department of Education, 2011

2011-01-01

The Office for Civil Rights (OCR) in the U.S. Department of Education (Department) is a law enforcement agency charged with enforcing federal civil rights laws to ensure that educational institutions receiving federal financial assistance do not engage in discriminatory conduct. OCR enforces the federal civil rights laws that prohibit…

Morbillivirus receptors and tropism: multiple pathways for infection

Directory of Open Access Journals (Sweden)

Hiroki eSato

2012-03-01

Full Text Available Morbilliviruses, which include measles virus (MeV, canine distemper virus, and rinderpest virus, are among the most important pathogens in their respective hosts and cause severe syndromes. Morbilliviruses are enveloped viruses with 2 envelope proteins, one of which is hemagglutinin (H protein, which plays a role in binding to cellular receptors. During morbillivirus infection, the virus initially targets lymphoid cells and replicates efficiently in the lymph nodes. The principal cellular receptor for morbillivirus is signaling lymphocyte activation molecule (SLAM, also called CD150, which is exclusively expressed on immune cells. This feature reflects the strong lymphoid cell tropism and viral spread in the infected body. Morbillivirus infection, however, affects various tissues in the body, including the lung, kidney, gastrointestinal tract, vascular endothelium, and brain. Thus, other receptors for morbilliviruses in addition to SLAM might exist. Recently, nectin-4 has been identified as a novel epithelial cell receptor for MeV. The expression of nectin-4 is localized to polarized epithelial cells, and this localization supports the notion of cell tropism since MeV also grows well in the epithelial cells of the respiratory tract. Although 2 major receptors for lymphoid and epithelial cells in natural infection have been identified, morbillivirus can still infect many other types of cells with low infectivity, suggesting the existence of inefficient but ubiquitously expressed receptors. We have identified other molecules that are implicated in morbillivirus infection of SLAM-negative cells by alternative mechanisms. These findings indicate that morbillivirus utilizes multiple pathways for establishment of infection. These studies will advance our understanding of morbillivirus tropism and pathogenesis.

Targeting transferrin receptors at the blood-brain barrier improves the uptake of immunoliposomes and subsequent cargo transport into the brain parenchyma

DEFF Research Database (Denmark)

Johnsen, Kasper B.; Burkhart, Annette; Melander, Fredrik

2017-01-01

Drug delivery to the brain is hampered by the presence of the blood-brain barrier, which excludes most molecules from freely diffusing into the brain, and tightly regulates the active transport mechanisms that ensure sufficient delivery of nutrients to the brain parenchyma. Harnessing the possibi...... cargo uptake in the brain endothelium and subsequent cargo transport into the brain. These findings suggest that transferrin receptor-targeting is a relevant strategy of increasing drug exposure to the brain....... investigate the possibility of delivering immunoliposomes and their encapsulated cargo to the brain via targeting of the transferrin receptor. We find that transferrin receptor-targeting increases the association between the immunoliposomes and primary endothelial cells in vitro, but that this does...... not correlate with increased cargo transcytosis. Furthermore, we show that the transferrin receptor-targeted immunoliposomes accumulate along the microvessels of the brains of rats, but find no evidence for transcytosis of the immunoliposome. Conversely, the increased accumulation correlated both with increased...

Reduction of the protective effect of β-receptor inhibitors on E.coli bacteria

International Nuclear Information System (INIS)

Zywietz, F.; Brueckner, V.; Linden, W.

1974-01-01

Bacteria of E.coli B/r strain were tested with selenium-substituted amino acids for effects concerning radiation protection. Selenium-methionine was used for the tests. The B-receptor blocker Propanolol (Docitonsup(R)) was applied additionally. The irradiation was carried out on a 200 kV-γ-ray unit with a dose rate of 1,000 R/min. For selenium-methionine a maximum dose reduction factor (DRF) of 1.8 was found. The results of the present tests show that the radiation resistance-increasing effect of the protective substances used here, selenium methionine and cystein, was eliminated partially or totally by the β-receptor blocker. To what extent the development of a substance receptor complex important for the efficiency of AMP mechanism is prevented by the receptor blocker must be seen from further experiments. (GSE) [de

First cytoplasmic loop of glucagon-like peptide-1 receptor can function at the third cytoplasmic loop position of rhodopsin.

Science.gov (United States)

Yamashita, Takahiro; Tose, Koji; Shichida, Yoshinori

2008-01-01

G protein-coupled receptors (GPCRs) are classified into several families based on their amino acid sequences. In family 1, GPCRs such as rhodopsin and adrenergic receptor, the structure-function relationship has been extensively investigated to demonstrate that exposure of the third cytoplasmic loop is essential for selective G protein activation. In contrast, much less is known about other families. Here we prepared chimeric mutants between Gt-coupled rhodopsin and Gi/Go- and Gs-coupled glucagon-like peptide-1 (GLP-1) receptor of family 2 and tried to identify the loop region that functions at the third cytoplasmic loop position of rhodopsin. We succeeded in expressing a mutant having the first cytoplasmic loop of GLP-1 receptor and found that this mutant activated Gi and Go efficiently but did not activate Gt. Moreover, the rhodopsin mutant having the first loop of Gs-coupled secretin receptor of family 2 decreased the Gi and Go activation efficiencies. Therefore, the first loop of GLP-1 receptor would share a similar role to the third loop of rhodopsin in G protein activation. This result strongly suggested that different families of GPCRs have maintained molecular architectures of their ancestral types to generate a common mechanism, namely exposure of the cytoplasmic loop, to activate peripheral G protein.

High efficiency particulate removal with sintered metal filters

International Nuclear Information System (INIS)

Kirstein, B.E.; Paplawsky, W.J.; Pence, D.T.; Hedahl, T.G.

1981-01-01

Because of their particle removal efficiencies and durability, sintered metal filters have been chosen for high efficiency particulate air (HEPA) filter protection in the off-gas treatment system for the proposed Idaho National Engineering Laboratory Transuranic Waste Treatment Facility. Process evaluation of sintered metal filters indicated a lack of sufficient process design data to ensure trouble-free operation. Subsequence pilot scale testing was performed with flyash as the test particulate. The test results showed that the sintered metal filters can have an efficiency greater than 0.9999999 for the specific test conditions used. Stable pressure drop characteristics were observed in pulsed and reversed flow blowback modes of operation. Over 4900 hours of operation were obtained with operating conditions ranging up to approximately 90 0 C and 24 vol % water vapor in the gas stream

Enhancing Scientific Foundations to Ensure Reproducibility: A New Paradigm.

Science.gov (United States)

Hsieh, Terry; Vaickus, Max H; Remick, Daniel G

2018-01-01

Progress in science is dependent on a strong foundation of reliable results. The publish or perish paradigm in research, coupled with an increase in retracted articles from the peer-reviewed literature, is beginning to erode the trust of both the scientific community and the public. The NIH is combating errors by requiring investigators to follow new guidelines addressing scientific premise, experimental design, biological variables, and authentication of reagents. Herein, we discuss how implementation of NIH guidelines will help investigators proactively address pitfalls of experimental design and methods. Careful consideration of the variables contributing to reproducibility helps ensure robust results. The NIH, investigators, and journals must collaborate to ensure that quality science is funded, explored, and published. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Evaluating Reverse Supply Chain Efficiency: Manufacturer's Perspective

DEFF Research Database (Denmark)

Kumar, M.; Tiwari, M. K.; Wong, K. Y.

2014-01-01

The paper aims to illustrate the use of fuzzy data envelopment analysis (DEA) in analyzing reverse supply chain (RSC) performance from the manufacturer's perspective. By using an alternative alpha-cut approach, the fuzzy DEA model was converted into a crisp linear programming problem, thereby...... usually ensures an environmentally friendly supply chain network, companies which have implemented RSC techniques since a longer duration do not necessarily have a more efficient supply chain in general....

Ensuring the security and availability of a hospital wireless LAN system.

Science.gov (United States)

Hanada, Eisuke; Kudou, Takato; Tsumoto, Shusaku

2013-01-01

Wireless technologies as part of the data communication infrastructure of modern hospitals are being rapidly introduced. Even though there are concerns about problems associated with wireless communication security, the demand is remarkably large. Herein we discuss security countermeasures that must be taken and issues concerning availability that must be considered to ensure safe hospital/business use of wireless LAN systems, referring to the procedures introduced at a university hospital. Security countermeasures differ according to their purpose, such as preventing illegal use or ensuring availability, both of which are discussed. The main focus of the availability discussion is on signal reach, electromagnetic noise elimination, and maintaining power supply to the network apparatus. It is our hope that this information will assist others in their efforts to ensure safe implementation of wireless LAN systems, especially in hospitals where they have the potential to greatly improve information sharing and patient safety.

Potential and barrier study. Energy efficiency of Norwegian homes; Potensial- og barrierestudie. Energieffektivisering av norske boliger

Energy Technology Data Exchange (ETDEWEB)

NONE

2012-07-01

Enova has identified potentials and barriers for energy efficiency in Norwegian buildings. This report summarizes the results of this work. Efficient energy in buildings is important to ensure that future economic activity and growth can occur in a way that reduces the possibilities for an environmentally and economically sound development. (eb)

Receptor-Mediated Drug Delivery to Macrophages in Chemotherapy of Leishmaniasis

Science.gov (United States)

Mukhopadhyay, Amitabha; Chaudhuri, Gautam; Arora, Sunil K.; Sehgal, Shobha; Basu, Sandip K.

1989-05-01

Methotrexate coupled to maleylated bovine serum albumin was taken up efficiently through the ``scavenger'' receptors present on macrophages and led to selective killing of intracellular Leishmania mexicana amazonensis amastigotes in cultured hamster peritoneal macrophages. The drug conjugate was nearly 100 times as effective as free methotrexate in eliminating the intracellular parasites. Furthermore, in a model of experimental cutaneous leishmaniasis in hamsters, the drug conjugate brought about more than 90% reduction in the size of footpad lesions within 11 days. In contrast, the free drug at a similar concentration did not significantly affect lesion size. These studies demonstrate the potential of receptor-mediated drug delivery in the therapy of macrophage-associated diseases.

Partial functional complementation between human and mouse cytomegalovirus chemokine receptor homologues

DEFF Research Database (Denmark)

Farrell, Helen E; Abraham, Alexander M; Cardin, Rhonda D

2011-01-01

The human cytomegalovirus (CMV) proteins US28 and UL33 are homologous to chemokine receptors (CKRs). Knockout of the mouse CMV M33 protein (UL33 homologue) results in substantial attenuation of salivary gland infection/replication and reduced efficiency of reactivation from tissue explants. M33-m...

Flow Cytometry-Based Bead-Binding Assay for Measuring Receptor Ligand Specificity

NARCIS (Netherlands)

Sprokholt, Joris K.; Hertoghs, Nina; Geijtenbeek, Teunis B. H.

2016-01-01

In this chapter we describe a fluorescent bead-binding assay, which is an efficient and feasible method to measure interaction between ligands and receptors on cells. In principle, any ligand can be coated on fluorescent beads either directly or via antibodies. Binding between ligand-coated beads

Strategies for Ensuring Trustworthiness in Qualitative Research Projects

Science.gov (United States)

Shenton, Andrew K.

2004-01-01

Although many critics are reluctant to accept the trustworthiness of qualitative research, frameworks for ensuring rigour in this form of work have been in existence for many years. Guba's constructs, in particular, have won considerable favour and form the focus of this paper. Here researchers seek to satisfy four criteria. In addressing…

The interleukin-4 receptor: signal transduction by a hematopoietin receptor.

Science.gov (United States)

Keegan, A D; Pierce, J H

1994-02-01

Over the last several years, the receptors for numerous cytokines have been molecularly characterized. Analysis of their amino acid sequences shows that some of these receptors bear certain motifs in their extracellular domains that define a family of receptors called the Hematopoietin receptor superfamily. Significant advances in characterizing the structure, function, and mechanisms of signal transduction have been made for several members of this family. The purpose of this review is to discuss the recent advances made for one of the family members, the interleukin (IL) 4 receptor. Other receptor systems have recently been reviewed elsewhere. The IL-4 receptor consists of, at the minimum, the cloned 140 kDa IL-4-binding chain with the potential for associating with other chains. The IL-4 receptor transduces its signal by activating a tyrosine kinase that phosphorylates cellular substrates, including the receptor itself, and the 170 kDa substrate called 4PS. Phosphorylated 4PS interacts with the SH2 domain of the enzyme PI-3'-kinase and increases its enzymatic activity. These early events in the IL-4 receptor initiated signaling pathway may trigger a series of signals that will ultimately lead to an IL-4 specific biologic outcome.

ANTAGONISM OF PROGESTERONE RECEPTOR SUPPRESSES CAROTID BODY RESPONSES TO HYPOXIA AND NICOTINE IN RAT PUPS

Science.gov (United States)

JOSEPH, V.; NIANE, L. M.; BAIRAM, A.

2013-01-01

We tested the hypothesis that antagonism of progesterone receptor (PR) in newborn rats alters carotid body and respiratory responses to hypoxia and nicotinic receptor agonists. Rats were treated with the PR antagonist mifepristone (daily oral gavage 40 μg/g/d) or vehicle between post-natal days 3 and 15. In 11–14-day-old rats, we used in vitro carotid body/carotid sinus nerve preparation and whole body plethysmography to assess the carotid body and ventilatory responses to hypoxia (65 mmHg in vitro, 10% O2 in vivo) and to nicotinic receptor agonists (as an excitatory modulator of carotid body activity—nicotine 100 μM for in vitro studies, and epibatidine 5 μg/kg, i.p., which mainly acts on peripheral nicotinic receptors, for in vivo studies). The carotid body responses to hypoxia and nicotine were drastically reduced by mifepristone. Compared with vehicle, mifepristone-treated rats had a reduced body weight. The ventilatory response to epibatidine was attenuated; however, the hypoxic ventilatory response was similar between vehicle and mifepristone-treated pups. Immunohistochemical staining revealed that mifepristone treatment did not change carotid body morphology. We conclude that PR activity is a critical factor ensuring proper carotid body function in newborn rats. PMID:22326965

Role of Head Teachers in Ensuring Sound Climate

Science.gov (United States)

Kor, Jacob; Opare, James K.

2017-01-01

The school climate is outlined in literature as one of the most important within school factors required for effective teaching in learning. As leaders in any organisations are assigned the role of ensuring sound climates for work, head teachers also have the task of creating and maintaining an environment conducive for effective academic work…

An Energy Efficient Cooperative Hierarchical MIMO Clustering Scheme for Wireless Sensor Networks

Directory of Open Access Journals (Sweden)

Sungyoung Lee

2011-12-01

Full Text Available In this work, we present an energy efficient hierarchical cooperative clustering scheme for wireless sensor networks. Communication cost is a crucial factor in depleting the energy of sensor nodes. In the proposed scheme, nodes cooperate to form clusters at each level of network hierarchy ensuring maximal coverage and minimal energy expenditure with relatively uniform distribution of load within the network. Performance is enhanced by cooperative multiple-input multiple-output (MIMO communication ensuring energy efficiency for WSN deployments over large geographical areas. We test our scheme using TOSSIM and compare the proposed scheme with cooperative multiple-input multiple-output (CMIMO clustering scheme and traditional multihop Single-Input-Single-Output (SISO routing approach. Performance is evaluated on the basis of number of clusters, number of hops, energy consumption and network lifetime. Experimental results show significant energy conservation and increase in network lifetime as compared to existing schemes.

Toll-like receptor 3 signalling up-regulates expression of the HIV co-receptor G-protein coupled receptor 15 on human CD4+ T cells.

Directory of Open Access Journals (Sweden)

Miriam Kiene

Full Text Available BACKGROUND: Many HIV-2 and SIV isolates, as well as some HIV-1 strains, can use the orphan 7-transmembrane receptor GPR15 as co-receptor for efficient entry into host cells. GPR15 is expressed on central memory and effector memory CD4(+ T cells in healthy individuals and a subset of these cells is susceptible to HIV-1 and SIV infection. However, it has not been determined whether GPR15 expression is altered in the context of HIV-1 infection. RESULTS: Here, we show that GPR15 expression in CD4(+ T cells is markedly up-regulated in some HIV-1 infected individuals compared to the rest of the infected patients and to healthy controls. Infection of the PM1 T cell line with primary HIV-1 isolates was found to up-regulate GPR15 expression on the infected cells, indicating that viral components can induce GPR15 expression. Up-regulation of GPR15 expression on CD4(+ T cells was induced by activation of Toll-like receptor 3 signalling via TIR-domain-containing adapter-inducing interferon-β (TRIF and was more prominent on gut-homing compared to lymph node-homing CD4(+ T cells. CONCLUSION: These results suggest that infection-induced up-regulation of GPR15 expression could increase susceptibility of CD4(+ T cells to HIV infection and target cell availability in the gut in some infected individuals.

[Ensure - complete and balanced nutrition, convenient on work].

Science.gov (United States)

Kurenkov, A V; Iuriatin, A A

2013-01-01

The work conditions often may compromise a company ability to supply their employees with adequate, hot meals. For heavy labor workers and some office employees it is important to restore energy and nutrients with food, balanced in nutrients. The lack of adequate nutritive support can give a negative impact on different organs functions. One of the main principles of healthy nutrition is - diet must be balanced in nutrients. Which is easy to say, but difficult to implement, especially on some industries. Complete and balanced liquid and ready-to-use nutrition is new trend in nutrition of healthy people who cannot consume optimal diet, and in people with the risk of nutrient deficiencies. One-two packs of Ensure daily can significantly improve a worker ration. 2 and more packs could serve as a real complete and balanced lunch (>or=780 kcal). Also Ensure is easy to store and to deliver in distant places of work and can be recommended for use as a convenient, complete and balanced nutrition on work.

FACTOR IN ENSURING A BALANCED BUDGET NORTHERN TERRITORIES

Directory of Open Access Journals (Sweden)

Tatiana Anatol’evna Naidenova

2016-02-01

Full Text Available The main tools of sustainable development of the country as a whole and its individual regions are federal and regional budgets. At the same time a prerequisite for the use of this tool is its equilibrium. It is the basic principle of a responsible fiscal policy. The article describes the factors to equilibrium. on the budgets of the northern regions of the Russian Federation. The measures to ensure budgetary equilibrium in the northern regions of the Russian Federation are offered.The purpose of the article. Substantiating the measures to balance the budgets of the northern Russian Federation subjects on the basis of analysis of the factors that directly affect the mobilization of potential tax revenues to regional budgets.Method and methodology of work. Theoretical and empirical methods, analysis, synthesis, induction, deduction.Results of the study. To ensure factors unbalanced budgets northern territories. The proposals the balance of revenues and expenditures of the regional budgets of the northern regions of the Russian Federation are submitted.Application area. Finance authorities of subjects of the Russian Federation.

Towards the Automatic Detection of Efficient Computing Assets in a Heterogeneous Cloud Environment

OpenAIRE

Iglesias, Jesus Omana; Stokes, Nicola; Ventresque, Anthony; Murphy, Liam, B.E.; Thorburn, James

2013-01-01

peer-reviewed In a heterogeneous cloud environment, the manual grading of computing assets is the first step in the process of configuring IT infrastructures to ensure optimal utilization of resources. Grading the efficiency of computing assets is however, a difficult, subjective and time consuming manual task. Thus, an automatic efficiency grading algorithm is highly desirable. In this paper, we compare the effectiveness of the different criteria used in the manual gr...

Signaling properties and pharmacological analysis of two sulfakinin receptors from the red flour beetle, Tribolium castaneum.

Science.gov (United States)

Zels, Sven; Verlinden, Heleen; Dillen, Senne; Vleugels, Rut; Nachman, Ronald J; Vanden Broeck, Jozef

2014-01-01

Sulfakinin is an insect neuropeptide that constitutes an important component of the complex network of hormonal and neural factors that regulate feeding and digestion. The key modulating functions of sulfakinin are mediated by binding and signaling via G-protein coupled receptors. Although a substantial amount of functional data have already been reported on sulfakinins in different insect species, only little information is known regarding the properties of their respective receptors. In this study, we report on the molecular cloning, functional expression and characterization of two sulfakinin receptors in the red flour beetle, Tribolium castaneum. Both receptor open reading frames show extensive sequence similarity with annotated sulfakinin receptors from other insects. Comparison of the sulfakinin receptor sequences with homologous vertebrate cholecystokinin receptors reveals crucial conserved regions for ligand binding and receptor activation. Quantitative reverse transcriptase PCR shows that transcripts of both receptors are primarily expressed in the central nervous system of the beetle. Pharmacological characterization using 29 different peptide ligands clarified the essential requirements for efficient activation of these sulfakinin receptors. Analysis of the signaling pathway in multiple cell lines disclosed that the sulfakinin receptors of T. castaneum can stimulate both the Ca²⁺ and cyclic AMP second messenger pathways. This in depth characterization of two insect sulfakinin receptors may provide useful leads for the further development of receptor ligands with a potential applicability in pest control and crop protection.

A Comprehensive Solution of the Problems of Ensuring the Strength of Gas Turbine Engine Compressor at the Design Stage

Science.gov (United States)

Vedeneev, V. V.; Kolotnikov, M. E.; Mossakovskii, P. A.; Kostyreva, L. A.; Abdukhakimov, F. A.; Makarov, P. V.; Pyhalov, A. A.; Dudaev, M. A.

2018-01-01

In this paper we present a complex numerical workflow for analysis of blade flutter and high-amplitude resonant oscillations, impenetrability of casing if the blade is broken off, and the rotor reaction to the blade detachment and following misbalance, with the assessment of a safe flight possibility at the auto-rotation regime. All the methods used are carefully verified by numerical convergence study and correlations with experiments. The use of the workflow developed significantly improves the efficiency of the design process of modern jet engine compressors. It ensures a significant reduction of time and cost of the compressor design with the required level of strength and durability.

Future of Assurance: Ensuring that a System is Trustworthy

Science.gov (United States)

Sadeghi, Ahmad-Reza; Verbauwhede, Ingrid; Vishik, Claire

Significant efforts are put in defining and implementing strong security measures for all components of the comput-ing environment. It is equally important to be able to evaluate the strength and robustness of these measures and establish trust among the components of the computing environment based on parameters and attributes of these elements and best practices associated with their production and deployment. Today the inventory of techniques used for security assurance and to establish trust -- audit, security-conscious development process, cryptographic components, external evaluation - is somewhat limited. These methods have their indisputable strengths and have contributed significantly to the advancement in the area of security assurance. However, shorter product and tech-nology development cycles and the sheer complexity of modern digital systems and processes have begun to decrease the efficiency of these techniques. Moreover, these approaches and technologies address only some aspects of security assurance and, for the most part, evaluate assurance in a general design rather than an instance of a product. Additionally, various components of the computing environment participating in the same processes enjoy different levels of security assurance, making it difficult to ensure adequate levels of protection end-to-end. Finally, most evaluation methodologies rely on the knowledge and skill of the evaluators, making reliable assessments of trustworthiness of a system even harder to achieve. The paper outlines some issues in security assurance that apply across the board, with the focus on the trustworthiness and authenticity of hardware components and evaluates current approaches to assurance.

The LDL receptor.

Science.gov (United States)

Goldstein, Joseph L; Brown, Michael S

2009-04-01

In this article, the history of the LDL receptor is recounted by its codiscoverers. Their early work on the LDL receptor explained a genetic cause of heart attacks and led to new ways of thinking about cholesterol metabolism. The LDL receptor discovery also introduced three general concepts to cell biology: receptor-mediated endocytosis, receptor recycling, and feedback regulation of receptors. The latter concept provides the mechanism by which statins selectively lower plasma LDL, reducing heart attacks and prolonging life.

Strategy to Ensure Institutional Control Implementation at Superfund Sites

Science.gov (United States)

This document sets forth EPA’s strategy (Strategy) for ensuring that institutional controls (ICs) are successfully implemented at Superfund sites, with an emphasis on evaluating ICs at sites where all construction of all remedies is complete (construction complete sites).

An efficient nonlinear Feshbach engine

Science.gov (United States)

Li, Jing; Fogarty, Thomás; Campbell, Steve; Chen, Xi; Busch, Thomas

2018-01-01

We investigate a thermodynamic cycle using a Bose-Einstein condensate (BEC) with nonlinear interactions as the working medium. Exploiting Feshbach resonances to change the interaction strength of the BEC allows us to produce work by expanding and compressing the gas. To ensure a large power output from this engine these strokes must be performed on a short timescale, however such non-adiabatic strokes can create irreversible work which degrades the engine’s efficiency. To combat this, we design a shortcut to adiabaticity which can achieve an adiabatic-like evolution within a finite time, therefore significantly reducing the out-of-equilibrium excitations in the BEC. We investigate the effect of the shortcut to adiabaticity on the efficiency and power output of the engine and show that the tunable nonlinearity strength, modulated by Feshbach resonances, serves as a useful tool to enhance the system’s performance.

Promoting energy efficiency in developing countries: The role of NGOs

International Nuclear Information System (INIS)

Wojtaszek, E.I.

1993-06-01

Developing countries need energy growth to spur economic growth. Yet energy activities contribute significantly to local water pollution and global greenhouse gas emissions. Energy efficiency offers the means to achieve the twin goals of sustainable economic/social development and environmental protection. Energy efficiency increases industrial competitiveness and frees up capital so it can be applied to other uses, such as health and education. The key to improving energy efficiency in developing countries will be acquiring and applying Western technologies, practices, and policies and building national institutions for promoting energy efficiency. Relevant energy-efficient technologies include the use of better electric motors, adjustable speed controls, combined cycle power cogeneration, improved lighting, better refrigeration technologies, and improved electric power transmission and distribution systems. Western countries can best help developing countries by providing guidance and resources to support nongovernmental organizations (NGOS) staffed by local experts; these institutions can capture the energy efficiency potential and ensure environmental protection in developing countries

PROBLEMS OF HARMONIZATION OF THE GOALS AND VITAL INTERESTS IN ENSURING SOCIO-ECONOMIC SECURITY

Directory of Open Access Journals (Sweden)

D. N. Shvayba1

2017-01-01

Full Text Available Formation of an independent democratic Belarusian state is inextricably linked with transformations in all aspects of public life and, first of all, in economy. Economic reforms in Belarus are directed on creation of socially oriented market economic system, which will ensure the most efficient usage of resources at minimum social cost. In the social economy concepts of “equality” and “poverty” are considered as basic ones. Social security services are based on these concepts and role of the social security in any country is to reduce poverty and increase equality. In modern world poverty is uniquely associated with a low level of economic development and its eradication is the first step on the path to economic growth. As for inequality, such clear connection of this concept with economic development can not be traced. There are various theories explaining the impact of inequality on economic growth. However, they cannot be considered satisfactory because they predict opposite results. Several studies have universally postulated a security as protection of vital interests of a human being, society and State from internal and external threats. Vital interests comprise a set of needs and satisfaction of these needs reliably ensures existence and possibility of progressive development of a human being, society and State which are the main objects of the security. Presence of a hierarchical structure for organization of the system or its subsystems is an essential feature for any socio-economic system. The economy is a poly-hierarchical system. When considering the hierarchical structure of production management it is important to consider one property of the economic system that is incompleteness of information.

Effect of ensure on the oral bioavailability of gatifloxacin in healthy volunteers.

Science.gov (United States)

Kays, Michael B; Overholser, Brian R; Lagvankar, Seema; Goldman, Mitchell; Sowinski, Kevin M

2005-11-01

To determine the effect of Ensure on the relative oral bioavailability of gatifloxacin in healthy volunteers. Single-dose, randomized, crossover study. University-affiliated research center. Twelve healthy volunteers (six men, six women) aged 18 years or older with no clinically significant abnormal findings on physical examination or in medical history. Intervention. Subjects consumed 120 ml of study liquid-water or Ensure-every 30 minutes for five doses. With the second dose, subjects ingested a single gatifloxacin 400-mg tablet that had been uniformly crushed and mixed into the study liquid. Serial blood samples were collected for 48 hours, and gatifloxacin concentrations were determined by high-performance liquid chromatography. Pharmacokinetic data were analyzed by using noncompartmental methods. Maximum serum concentration (Cmax) and area under the serum concentration-time curve from zero to infinity (AUC0-infinity) were tested for bioequivalence after log-transformation of the data. Comparison of parameters for gatifloxacin administered with water versus those with Ensure showed that Cmax (4.35 +/- 0.90 vs 2.41 +/- 0.58 mug/ml, pinfinity) (42.4 +/- 10.1 vs 31.3 +/- 8.3 mg*hr/L, pinfinity. The median time to reach Cmax was significantly prolonged when gatifloxacin was administered with Ensure versus that with water (2.5 hrs vs 1.0 hr, p=0.006). The Cmax and AUC0-infinity of gatifloxacin were significantly decreased when the drug was administered with Ensure. The clinical significance of these findings will depend on the offending pathogen and its susceptibility to gatifloxacin.

Assessing the efficiency of priorities for traffic law enforcement in Norway

DEFF Research Database (Denmark)

Elvik, Rune; Sogge, Céline Vallet; Lager, Lasse

2012-01-01

attributable to them; and (3) an optimal level of enforcement is selected, i.e. the marginal benefits of enforcement in terms of preventing accidents equal the marginal costs of enforcement. The efficiency of current traffic law enforcement in Norway is assessed in terms of these criteria. It is found......This paper assesses the efficiency of priorities for traffic law enforcement in Norway. Priorities are regarded as efficient if: (1) enforcement ensures a sufficient level of deterrence to keep down the rate of violations; (2) selection of target violations for enforcement is based on the risk...... low. Cost-benefit analyses show that substantially increasing the amount of police enforcement is cost-effective....

Immediate challenge of combating climate change: Effective implementation of energy efficiency policies

Energy Technology Data Exchange (ETDEWEB)

Morvaj, Zoran; Bukarica, Vesna

2010-09-15

Energy efficiency is the most readily available, rapid and cost-effective way to achieve desired greenhouse gases reductions. Therefore, it is the focus of energy and climate change policies world wide. The results of these policies are still missing in the desired extent, even in the EU, which has the most advanced energy efficiency policy. The main reason behind this policy failure is a complete lack of focus on implementing capacities that would ensure full policy uptake. Embracing full-scale energy management systems in public and business sectors and mobilisation of and cooperation between all stakeholders are the way towards higher efficiency.

Ensuring the operational safety of nuclear power plants with WWER reactors

International Nuclear Information System (INIS)

Shasharin, G.A.; Veretennikov, G.A.; Abagyan, A.A.; Lesnoj, S.A.

1984-01-01

At the start of 1983, 27 nuclear power producing units with reactor facilities of the WWER type were in operation in the Soviet Union and other countries. In 1982 the average load factor for nuclear power plants with WWER reactors was 73 per cent. There was not a single nuclear accident or even damage with any significant radiation consequences in the WWER reactors during the entire period of their operation. The most modern nuclear power plants with WWER-440 and WWER-1000 reactors meet all present-day international requirements. Safe operation of the plants is achieved by a variety of measures, the most important of which include: procedures for increasing the reliability of plant equipment and systems; ensuring exact compliance with plant operating instructions; ensuring reliable operation of plant safety systems; action directed towards maintaining the skills of plant personnel at a level adequate to ensure the taking of proper action during transient processes and accident situations. The paper discusses concrete steps for ensuring safe nuclear power plant operation along these lines. In particular, measures such as the following are described: the use of a system for collecting and processing information on equipment failures and defects; the development and introduction of methods of early defect diagnosis; the performance of complex testing of safety systems; the training of highly skilled personnel for nuclear power plants at educational combines and at teaching and training centres making use of simulators; arranging accident-prevention training and special instruction for personnel. (author)

The moral economy of the digital welfare state: fostering efficiency and nurturing neoliberalism

DEFF Research Database (Denmark)

Schou, Jannick; Hjelholt, Morten

2017-01-01

prominent position, being seen as a way of renewing democracy by ensuring participation, transparency and inclusion of citizens. However, from 2001, economic efficiency, growth, and competitiveness have become the dominating moral claims attached to digitalization, replacing previous ideals with neoliberal...

Dopamine D2L receptor-interacting proteins regulate dopaminergic signaling

Directory of Open Access Journals (Sweden)

Norifumi Shioda

2017-10-01

Full Text Available Dopamine receptor family proteins include seven transmembrane and trimeric GTP-binding protein-coupled receptors (GPCRs. Among them, the dopamine D2 receptor (D2R is most extensively studied. All clinically used antipsychotic drugs serve as D2R antagonists in the mesolimbic dopamine system, and their ability to block D2R signaling is positively correlated with antipsychotic efficiency. Human genetic studies also show a significant association of DRD2 polymorphisms with disorders including schizophrenia and Parkinson's disease. D2R exists as two alternatively spliced isoforms, the long isoform (D2LR and the short isoform (D2SR, which differ in a 29-amino acid (AA insert in the third cytoplasmic loop. Importantly, previous reports demonstrate functional diversity between the two isoforms in humans. In this review, we focus on binding proteins that specifically interact with the D2LR 29AA insert. We discuss how D2R activities are mediated not only by heterotrimeric G proteins but by D2LR-interacting proteins, which in part regulate diverse D2R activities. Keywords: Dopamine D2L receptor, Antipsychotic drugs, DRD2 polymorphisms, Alternatively spliced isoforms, D2LR-interacting proteins

Ensuring Integrity in AGU Publications and Compliance With Dual Publication Policy

Science.gov (United States)

Kumar, Praveen; Calais, Eric

2011-03-01

To ensure the highest standards for publication, AGU has begun screening manuscript submissions using CrossCheck (http://www.crossref.org/crosscheck.html) for possible verbatim use of previously published material. Water Resources Research and Geophysical Research Letters have tested this technology since summer 2010. It has proven very useful in ensuring the highest integrity in publication standards and compliance with the AGU dual publication policy (http://www.agu.org/pubs/authors/policies/dualpub_policy.shtml). According to Barbara Major, assistant director of journals, other AGU journals will adopt this screening process in the near future.

Definition of a proper institutional and legal framweork to promote energy efficiency in Uruguay

Energy Technology Data Exchange (ETDEWEB)

Blanco, Alfonso; Juarez, Maria

2010-09-15

There is no lower cost energy source than the avoided energy from unnecessary consumption either more expensive energy than scarce energy resources in a growing economy. Under this concept energy efficiency has been established as one of the main pillars of energy policy in Uruguay since 2005. A recently approved Law provides 4-axis of action to promote energy efficiency: building of institutional structure and long-term framework necessary for nationwide development, ensuring consumers access to adequate information, facilitating the access to finance and economic resources to encourage energy efficiency projects and, removing tax and administrative barriers to energy efficiency.

Technical Education as a Tool for Ensuring Sustainable Development: A Case of India

Science.gov (United States)

Sharma, Gagan Deep; Uppal, Raminder Singh; Mahendru, Mandeep

2016-01-01

This paper notes that education needs to essentially lead to sustainable development serving two-fold purpose--eradicating the problems of unemployment and poverty; and ensuring equitable distribution of wealth while ensuring the right understanding leading to a peaceful, prosperous and developed world. In its current state, technical education…

β-Adrenergic receptor-mediated suppression of interleukin 2 receptors in human lymphocytes

International Nuclear Information System (INIS)

Feldman, R.D.; Hunninghake, G.W.; McArdle, W.L.

1987-01-01

Adrenergic receptor agonists are know to attenuate the proliferative response of human lymphocytes after activation; however, their mechanism of action is unknown. Since expression of interleukin 2 (IL-2) receptors is a prerequisite for proliferation, the effect of β-adrenergic receptor agonists on lymphocyte IL-2 receptors was studied on both mitogen-stimulated lymphocytes and IL-2-dependent T lymphocyte cell lines. In both cell types the β-adrenergic receptor agonist isoproterenol blocked the expression of IL-2 receptors, as determined with the IL-2 receptor anti-TAC antibody. To determine the effect of β-adrenergic agonists on expression of the high affinity IL-2 receptors, [ 125 I]IL-2 binding studies were performed at concentrations selective for high affinity sites. No significant effect of β-adrenergic agonists on high affinity IL-2 receptor sites could be detected. The data demonstrate that β-adrenergic receptor agonists down-regulate IL-2 receptors primarily affecting low affinity sites

Targeting transferrin receptors at the blood-brain barrier improves the uptake of immunoliposomes and subsequent cargo transport into the brain parenchyma.

Science.gov (United States)

Johnsen, Kasper Bendix; Burkhart, Annette; Melander, Fredrik; Kempen, Paul Joseph; Vejlebo, Jonas Bruun; Siupka, Piotr; Nielsen, Morten Schallburg; Andresen, Thomas Lars; Moos, Torben

2017-09-04

Drug delivery to the brain is hampered by the presence of the blood-brain barrier, which excludes most molecules from freely diffusing into the brain, and tightly regulates the active transport mechanisms that ensure sufficient delivery of nutrients to the brain parenchyma. Harnessing the possibility of delivering neuroactive drugs by way of receptors already present on the brain endothelium has been of interest for many years. The transferrin receptor is of special interest since its expression is limited to the endothelium of the brain as opposed to peripheral endothelium. Here, we investigate the possibility of delivering immunoliposomes and their encapsulated cargo to the brain via targeting of the transferrin receptor. We find that transferrin receptor-targeting increases the association between the immunoliposomes and primary endothelial cells in vitro, but that this does not correlate with increased cargo transcytosis. Furthermore, we show that the transferrin receptor-targeted immunoliposomes accumulate along the microvessels of the brains of rats, but find no evidence for transcytosis of the immunoliposome. Conversely, the increased accumulation correlated both with increased cargo uptake in the brain endothelium and subsequent cargo transport into the brain. These findings suggest that transferrin receptor-targeting is a relevant strategy of increasing drug exposure to the brain.

Quantitative receptor radioautography in the study of receptor-receptor interactions in the nucleus tractus solitarii

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Fior-Chadi D.R.

1998-01-01

Full Text Available The nucleus tractus solitarii (NTS in the dorsomedial medulla comprises a wide range of neuropeptides and biogenic amines. Several of them are related to mechanisms of central blood pressure control. Angiotensin II (Ang II, neuropeptide Y (NPY and noradrenaline (NA are found in the NTS cells, as well as their receptors. Based on this observation we have evaluated the modulatory effect of these peptide receptors on a2-adrenoceptors in the NTS. Using quantitative receptor radioautography, we observed that NPY and Ang II receptors decreased the affinity of a2-adrenoceptors for their agonists in the NTS of the rat. Cardiovascular experiments agreed with the in vitro data. Coinjection of a threshold dose of Ang II or of the NPY agonists together with an ED50 dose of adrenergic agonists such as NA, adrenaline and clonidine counteracted the depressor effect produced by the a2-agonist in the NTS. The results provide evidence for the existence of an antagonistic interaction between Ang II at1 receptors and NPY receptor subtypes with the a2-adrenoceptors in the NTS. This receptor interaction may reduce the transduction over the a2-adrenoceptors which can be important in central cardiovascular regulation and in the development of hypertension

Effects of epidermal growth factor, transferrin, and insulin on lipofection efficiency in human lung carcinoma cells.

Science.gov (United States)

Yanagihara, K; Cheng, H; Cheng, P W

2000-01-01

Poor transfection efficiency is the major drawback of lipofection. We showed previously that addition of transferrin (TF) to Lipofectin enhanced the expression of a reporter gene in HeLa cells by 120-fold and achieved close to 100% transfection efficiency. The purpose of this study was to determine whether TF and other ligands could improve the efficiency of lipofection in lung carcinoma cells. Confluent A549, Calu3, and H292 cells were transfected for 18 hours with a plasmid DNA (pCMVlacZ) using Lipofectin plus TF, insulin, or epidermal growth factor as the vector. The transfected cells were assessed for transfection efficiency by beta-galactosidase activity (light units/microg protein) and the percentage of blue cells following 5-bromo-4-chloro-3-indolyl beta-D-galactopyranoside staining. Lipofectin supplemented with epidermal growth factor yielded the largest enhancement of lipofection efficiency (lipofection efficiency in A549 and Calu3 cells but not in H292 cells, whereas TF showed significant lipofection efficiency-enhancing effect in Calu3 and H292 cells but not in A549 cells. The transfection efficiency correlated well with the amounts of DNA delivered to the nucleus as well as the amounts of the receptor. These results indicate that the gene delivery strategy employing ligand-facilitated lipofection can achieve high transfection efficiency in human lung carcinoma cells. In addition, enhancement of the expression of the receptor may be a possible strategy for increasing the efficiency of gene targeting.

Energy Efficient Monitoring for Intrusion Detection in Battery-Powered Wireless Mesh Networks

KAUST Repository

Hassanzadeh, Amin

2011-07-18

Wireless Mesh Networks (WMN) are easy-to-deploy, low cost solutions for providing networking and internet services in environments with no network infrastructure, e.g., disaster areas and battlefields. Since electric power is not readily available in such environments battery-powered mesh routers, operating in an energy efficient manner, are required. To the best of our knowledge, the impact of energy efficient solutions, e.g., involving duty-cycling, on WMN intrusion detection systems, which require continuous monitoring, remains an open research problem. In this paper we propose that carefully chosen monitoring mesh nodes ensure continuous and complete detection coverage, while allowing non-monitoring mesh nodes to save energy through duty-cycling. We formulate the monitoring node selection problem as an optimization problem and propose distributed and centralized solutions for it, with different tradeoffs. Through extensive simulations and a proof-of-concept hardware/software implementation we demonstrate that our solutions extend the WMN lifetime by 8%, while ensuring, at the minimum, a 97% intrusion detection rate.

Ensuring Economic Security in Lending Sphere

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Ivan Vadimovich Kochikin

2016-06-01

Full Text Available Relevance of the topic is determined by the need for sustainable development of the country’s banking system, capable of ensuring the process of raising funds to producers and the public for their projects. One of the implementation of this objective is to discourage unfair behavior in financial markets. Trust is a key factor in the development of financial markets, therefore it is necessary to suppress the appearance of unfair practices and participants – black creditors, falsification of financial statements, trading on insider information and market manipulation. It requires a whole range of activities, and above all ensuring the inevitability and proportionality of punishment for unscrupulous players, the introduction of requirements for the business reputation of the management of financial institutions.The article is devoted to structuring legal violations in the lending sphere. The analysis of indicators of credit organizations in Russia was conducted to fulfill this aim. This analysis revealed the causes of sustainable growth of overdue accounts payable – job cuts in enterprises, violations in the financial sector, various errors in the credit granting / raising. The authors carry out the systematization and classification of offenses in the area of lending, provide examples, as well as factual material illustrating the violations in the lending process having the characteristics of a fraud. The article substantiates the obligations of employees of the credit institution, in the result of which risks of granting credit to fraudsters can be reduced. The methods of fraud prevention should include the identified methods of protection against fraud in the area under consideration – exchange of information by banks associated with the criminal intentions of customers; technology development and technical support, training, and personnel responsibilities.

Achieving a golden mean: mechanisms by which coronaviruses ensure synthesis of the correct stoichiometric ratios of viral proteins.

Science.gov (United States)

Plant, Ewan P; Rakauskaite, Rasa; Taylor, Deborah R; Dinman, Jonathan D

2010-05-01

In retroviruses and the double-stranded RNA totiviruses, the efficiency of programmed -1 ribosomal frameshifting is critical for ensuring the proper ratios of upstream-encoded capsid proteins to downstream-encoded replicase enzymes. The genomic organizations of many other frameshifting viruses, including the coronaviruses, are very different, in that their upstream open reading frames encode nonstructural proteins, the frameshift-dependent downstream open reading frames encode enzymes involved in transcription and replication, and their structural proteins are encoded by subgenomic mRNAs. The biological significance of frameshifting efficiency and how the relative ratios of proteins encoded by the upstream and downstream open reading frames affect virus propagation has not been explored before. Here, three different strategies were employed to test the hypothesis that the -1 PRF signals of coronaviruses have evolved to produce the correct ratios of upstream- to downstream-encoded proteins. Specifically, infectious clones of the severe acute respiratory syndrome (SARS)-associated coronavirus harboring mutations that lower frameshift efficiency decreased infectivity by >4 orders of magnitude. Second, a series of frameshift-promoting mRNA pseudoknot mutants was employed to demonstrate that the frameshift signals of the SARS-associated coronavirus and mouse hepatitis virus have evolved to promote optimal frameshift efficiencies. Finally, we show that a previously described frameshift attenuator element does not actually affect frameshifting per se but rather serves to limit the fraction of ribosomes available for frameshifting. The findings of these analyses all support a "golden mean" model in which viruses use both programmed ribosomal frameshifting and translational attenuation to control the relative ratios of their encoded proteins.

Ensuring quality control of forensic accounting for efficient and ...

African Journals Online (AJOL)

Global Journal of Social Sciences. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 12, No 1 (2013) >. Log in or Register to get access to full text downloads.

Distinctive receptor binding properties of the surface glycoprotein of a natural Feline Leukemia Virus isolate with unusual disease spectrum

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Albritton Lorraine M

2011-05-01

Full Text Available Abstract Background Feline leukemia virus (FeLV-945, a member of the FeLV-A subgroup, was previously isolated from a cohort of naturally infected cats. An unusual multicentric lymphoma of non-T-cell origin was observed in natural and experimental infection with FeLV-945. Previous studies implicated the FeLV-945 surface glycoprotein (SU as a determinant of disease outcome by an as yet unknown mechanism. The present studies demonstrate that FeLV-945 SU confers distinctive properties of binding to the cell surface receptor. Results Virions bearing the FeLV-945 Env protein were observed to bind the cell surface receptor with significantly increased efficiency, as was soluble FeLV-945 SU protein, as compared to the corresponding virions or soluble protein from a prototype FeLV-A isolate. SU proteins cloned from other cohort isolates exhibited increased binding efficiency comparable to or greater than FeLV-945 SU. Mutational analysis implicated a domain containing variable region B (VRB to be the major determinant of increased receptor binding, and identified a single residue, valine 186, to be responsible for the effect. Conclusions The FeLV-945 SU protein binds its cell surface receptor, feTHTR1, with significantly greater efficiency than does that of prototype FeLV-A (FeLV-A/61E when present on the surface of virus particles or in soluble form, demonstrating a 2-fold difference in the relative dissociation constant. The results implicate a single residue, valine 186, as the major determinant of increased binding affinity. Computational modeling suggests a molecular mechanism by which residue 186 interacts with the receptor-binding domain through residue glutamine 110 to effect increased binding affinity. Through its increased receptor binding affinity, FeLV-945 SU might function in pathogenesis by increasing the rate of virus entry and spread in vivo, or by facilitating entry into a novel target cell with a low receptor density.

A bovine papillomavirus-1 based vector restores the function of the low-density lipoprotein receptor in the receptor-deficient CHO-ldlA7 cell line

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Ustav Mart

2002-04-01

Full Text Available Abstract Background The rationale of using bovine papillomavirus-1 (BPV-1 derived vectors in gene therapy protocols lies in their episomal maintenance at intermediate to high copy number, and stable, high-level expression of the gene products. We constructed the BPV-1 based vector harbouring the human low-density lipoprotein receptor (LDLR gene cDNA and tested its ability to restore the function of the LDLR in the receptor-deficient cell line CHO-ldlA7. Results The introduced vector p3.7LDL produced functionally active LDL receptors in the receptor-deficient cell line CHO-ldlA7 during the 32-week period of observation as determined by the internalisation assay with the labelled LDL particles. Conclusion Bovine papillomavirus type-1 (BPV-1-derived vectors could be suitable for gene therapy due to their episomal maintenance at intermediate to high copy number and stable, high-level expression of the gene products. The constructed BPV-1 based vector p3.7LDL produced functionally active LDL receptors in the LDLR-deficient cell line CHO-ldlA7 during the 32-week period of observation. In vivo experiments should reveal, whether 1–5% transfection efficiency obtained in the current work is sufficient to bring about detectable and clinically significant lowering of the amount of circulating LDL cholesterol particles.

Signaling properties and pharmacological analysis of two sulfakinin receptors from the red flour beetle, Tribolium castaneum.

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Sven Zels

Full Text Available Sulfakinin is an insect neuropeptide that constitutes an important component of the complex network of hormonal and neural factors that regulate feeding and digestion. The key modulating functions of sulfakinin are mediated by binding and signaling via G-protein coupled receptors. Although a substantial amount of functional data have already been reported on sulfakinins in different insect species, only little information is known regarding the properties of their respective receptors. In this study, we report on the molecular cloning, functional expression and characterization of two sulfakinin receptors in the red flour beetle, Tribolium castaneum. Both receptor open reading frames show extensive sequence similarity with annotated sulfakinin receptors from other insects. Comparison of the sulfakinin receptor sequences with homologous vertebrate cholecystokinin receptors reveals crucial conserved regions for ligand binding and receptor activation. Quantitative reverse transcriptase PCR shows that transcripts of both receptors are primarily expressed in the central nervous system of the beetle. Pharmacological characterization using 29 different peptide ligands clarified the essential requirements for efficient activation of these sulfakinin receptors. Analysis of the signaling pathway in multiple cell lines disclosed that the sulfakinin receptors of T. castaneum can stimulate both the Ca²⁺ and cyclic AMP second messenger pathways. This in depth characterization of two insect sulfakinin receptors may provide useful leads for the further development of receptor ligands with a potential applicability in pest control and crop protection.

ReFlexIn: a flexible receptor protein-ligand docking scheme evaluated on HIV-1 protease.

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Simon Leis

Full Text Available For many targets of pharmaceutical importance conformational changes of the receptor protein are relevant during the ligand binding process. A new docking approach, ReFlexIn (Receptor Flexibility by Interpolation, that combines receptor flexibility with the computationally efficient potential grid representation of receptor molecules has been evaluated on the retroviral HIV-1 (Human Immunodeficiency Virus 1 protease system. An approximate inclusion of receptor flexibility is achieved by using interpolation between grid representations of individual receptor conformations. For the retroviral protease the method was tested on an ensemble of protease structures crystallized in the presence of different ligands and on a set of structures obtained from morphing between the unbound and a ligand-bound protease structure. Docking was performed on ligands known to bind to the protease and several non-binders. For the binders the ReFlexIn method yielded in almost all cases ligand placements in similar or closer agreement with experiment than docking to any of the ensemble members without degrading the discrimination with respect to non-binders. The improved docking performance compared to docking to rigid receptors allows for systematic virtual screening applications at very small additional computational cost.

XMRV: usage of receptors and potential co-receptors

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Gaddam Durga

2011-09-01

Full Text Available Abstract Background XMRV is a gammaretrovirus first identified in prostate tissues of Prostate Cancer (PC patients and later in the blood cells of patients with Chronic Fatigue Syndrome (CFS. Although XMRV is thought to use XPR1 for cell entry, it infects A549 cells that do not express XPR1, suggesting usage of other receptors or co-receptors. Methods To study the usage of different receptors and co- receptors that could play a role in XMRV infection of lymphoid cells and GHOST (GFP- Human osteosarcoma cells expressing CD4 along with different chemokine receptors including CCR1, CCR2, etc., were infected with XMRV. Culture supernatants and cells were tested for XMRV replication using real time quantitative PCR. Results Infection and replication of XMRV was seen in a variety of GHOST cells, LNCaP, DU145, A549 and Caski cell lines. The levels of XMRV replication varied in different cell lines showing differential replication in different cell lines. However, replication in A549 which lacks XPR1 expression was relatively higher than DU145 but lower than, LNCaP. XMRV replication varied in GHOST cell lines expressing CD4 and each of the co- receptors CCR1-CCR8 and bob. There was significant replication of XMRV in CCR3 and Bonzo although it is much lower when compared to DU145, A549 and LNCaP. Conclusion XMRV replication was observed in GHOST cells that express CD4 and each of the chemokine receptors ranging from CCR1- CCR8 and BOB suggesting that infectivity in hematopoietic cells could be mediated by use of these receptors.

Targeting Multiple Tumors Using T-Cells Engineered to Express a Natural Cytotoxicity Receptor 2-Based Chimeric Receptor

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Vasyl Eisenberg

2017-09-01

Full Text Available Recent developments in cancer treatment are demonstrating the increasing and powerful potential of immunotherapeutic strategies. In this regard, the adoptive transfer of tumor-specific T-lymphocytes approaches can lead to tumor regression in cancer patients. More recently, the use of T-cells genetically engineered to express cancer-specific receptors such as the anti-CD19 chimeric antigen receptor (CAR continues to show promise for the treatment of hematological malignancies. Still, there is a crucial need to develop efficient CAR-T cell approaches for the treatment of solid tumors. It has been shown that other lymphocytes such as natural killer (NK cells can demonstrate potent antitumor function—nonetheless, their use in immunotherapy is rather limited due to difficulties in expanding these cells to therapeutically relevant numbers and to suppression by endogenous inhibitory mechanisms. Cancer recognition by NK cells is partly mediated by molecules termed natural cytotoxicity receptors (NCRs. In the present study, we hypothesize that it is possible to endow T-cells with an NK recognition pattern, providing them with a mean to recognize tumor cells, in a non-MHC restricted way. To test this, we genetically modified human T-cells with different chimeric receptors based on the human NCR2 molecule and then assessed their antitumor activity in vitro and in vivo. Our results show that expression in primary lymphocytes of an NCR2-derived CAR, termed s4428z, confers T-cells with the ability to specifically recognize heterogeneous tumors and to mediate tumor cytotoxicity in a mouse model. This study demonstrates the benefit of combining tumor recognition capability of NK cells with T cell effectiveness to improve cancer immunotherapy.

GABA receptor imaging

Energy Technology Data Exchange (ETDEWEB)

Lee, Jong Doo [Yonsei University College of Medicine, Seoul (Korea, Republic of)

2007-04-15

GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABA{sub A}-receptor that allows chloride to pass through a ligand gated ion channel and GABA{sub B}-receptor that uses G-proteins for signaling. The GABA{sub A}-receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABA{sub A}-receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with {sup 11}C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, {sup 18}F-fluoroflumazenil (FFMZ) has been developed to overcome {sup 11}C's short half-life. {sup 18}F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '1{sup 1}C-FMZ PET instead of {sup 18}F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABA{sub A} receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas.

GABA receptor imaging

International Nuclear Information System (INIS)

Lee, Jong Doo

2007-01-01

GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABA A -receptor that allows chloride to pass through a ligand gated ion channel and GABA B -receptor that uses G-proteins for signaling. The GABA A -receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABA A -receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with 11 C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, 18 F-fluoroflumazenil (FFMZ) has been developed to overcome 11 C's short half-life. 18 F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '1 1 C-FMZ PET instead of 18 F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABA A receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas

Novel targeted approaches to treating biliary tract cancer: the dual epidermal growth factor receptor and ErbB-2 tyrosine kinase inhibitor NVP-AEE788 is more efficient than the epidermal growth factor receptor inhibitors gefitinib and erlotinib.

Science.gov (United States)

Wiedmann, Marcus; Feisthammel, Jürgen; Blüthner, Thilo; Tannapfel, Andrea; Kamenz, Thomas; Kluge, Annett; Mössner, Joachim; Caca, Karel

2006-08-01

Aberrant activation of the epidermal growth factor receptor is frequently observed in neoplasia, notably in tumors of epithelial origin. Attempts to treat such tumors with epidermal growth factor receptor antagonists resulted in remarkable success in recent studies. Little is known, however, about the efficacy of this therapy in biliary tract cancer. Protein expression of epidermal growth factor receptor, ErbB-2, and vascular endothelial growth factor receptor-2 was assessed in seven human biliary tract cancer cell lines by immunoblotting. In addition, histological sections from 19 patients with extrahepatic cholangiocarcinoma were analyzed for epidermal growth factor receptor, ErbB-2 and vascular endothelial growth factor receptor-2 expression by immunohistochemistry. Moreover, we sequenced the cDNA products representing the entire epidermal growth factor receptor coding region of the seven cell lines, and searched for genomic epidermal growth factor receptor amplifications and polysomy by fluorescence in-situ hybridization. Cell growth inhibition by gefitinib erlotinib and NVP-AEE788 was studied in vitro by automated cell counting. In addition, the anti-tumoral effect of erlotinib and NVP-AEE788 was studied in a chimeric mouse model. The anti-tumoral drug mechanism in this model was assessed by MIB-1 antibody staining, terminal deoxynucleotidyl transfer-mediated dUTP nick end-labelling assay, von Willebrand factor staining, and immunoblotting for p-p42/44 (p-Erk1/2, p-MAPK) and p-AKT. Immunoblotting revealed expression of epidermal growth factor receptor, ErbB-2, and vascular endothelial growth factor receptor-2 in all biliary tract cancer cell lines. EGFR was detectable in six of 19 (32%) extrahepatic human cholangiocarcinoma tissue samples, ErbB-2 in 16 of 19 (84%), and vascular endothelial growth factor receptor-2 in nine of 19 (47%). Neither epidermal growth factor receptor mutations nor amplifications or polysomy were found in the seven biliary tract cancer

Experimental study of the role of blocking of 5-HT3 serotonin receptors and D2 dophamin receptors in the mechanism of early radiation vomiting in monkeys

International Nuclear Information System (INIS)

Martirosov, K.S.; Grigor'ev, Yu.G.; Zorin, V.V.; Andrianova, I.E.

2000-01-01

Specific activity of Latranum and Dimetphramidum is studied using experimental model of early radiation vomiting on 17 monkeys, mass 6-9 kg inherent on usual ration of vivarium. The experiments with M. fasciculata monkeys exposed to 137 Cs γ-radiation with a dose of 6.9 Gy showed that Latranum, a blocker of serotonin 5-HT 3 receptors, is a more efficient antimetric than Dimetphramidum, a D 2 dophamin lytic. This suggested by fewer animals with emetic reaction of by less severe vomiting in case they have any. The results agree well with a hypothesis that serotonin receptors are dominant in the chemoreceptor trigger zone of monkeys [ru

The Conceptual Framework for Ensuring Economic Safety of Corporate Integration Processes

Directory of Open Access Journals (Sweden)

Gutsaliuk Oleksii M.

2016-08-01

Full Text Available The objective growth of the number of displays and influence of negative factors of threats from the environment actualizes the issue of ensuring economic safety of national economic entities. The article notes that simultaneously with counteracting threats enterprises are working for development, one form of which is the establishment of corporate structures and implementation of integration processes. It is proposed to ensure achieving the desired level of the corporate structure economic safety through optimizing the correlation of resources and competencies, skills and technologies for their use within the integrated logistics value chain. In this case it is the implementation of the integration process that serves as an instrument for achieving this optimal correlation, and the level of economic safety is considered as one of the optimization criteria. The system of authors’ hypotheses is taken as the basis for ensuring economic safety of the corporate integration process. Each of the hypotheses corresponds to a set of conceptual principles aimed at practical implementation of the proposed approaches. Within these conceptual principles the relationship between incentives and benefits of integration and the basis for ensuring their safety is presented, the differences between safety of functioning and safety of development are studied, the use of the methodology of logistics to harmonize the interests of participants of the corporate structure is justified, the relevance of applying the resource approach to manage the integration and development safety is proved. The graphical representation of causal relationships between the proposed conceptual principles allowed formalizing the subject area of studying corporate integration safety

The two-state dimer receptor model: a general model for receptor dimers.

Science.gov (United States)

Franco, Rafael; Casadó, Vicent; Mallol, Josefa; Ferrada, Carla; Ferré, Sergi; Fuxe, Kjell; Cortés, Antoni; Ciruela, Francisco; Lluis, Carmen; Canela, Enric I

2006-06-01

Nonlinear Scatchard plots are often found for agonist binding to G-protein-coupled receptors. Because there is clear evidence of receptor dimerization, these nonlinear Scatchard plots can reflect cooperativity on agonist binding to the two binding sites in the dimer. According to this, the "two-state dimer receptor model" has been recently derived. In this article, the performance of the model has been analyzed in fitting data of agonist binding to A(1) adenosine receptors, which are an example of receptor displaying concave downward Scatchard plots. Analysis of agonist/antagonist competition data for dopamine D(1) receptors using the two-state dimer receptor model has also been performed. Although fitting to the two-state dimer receptor model was similar to the fitting to the "two-independent-site receptor model", the former is simpler, and a discrimination test selects the two-state dimer receptor model as the best. This model was also very robust in fitting data of estrogen binding to the estrogen receptor, for which Scatchard plots are concave upward. On the one hand, the model would predict the already demonstrated existence of estrogen receptor dimers. On the other hand, the model would predict that concave upward Scatchard plots reflect positive cooperativity, which can be neither predicted nor explained by assuming the existence of two different affinity states. In summary, the two-state dimer receptor model is good for fitting data of binding to dimeric receptors displaying either linear, concave upward, or concave downward Scatchard plots.

Efficient gene transfer into lymphoma cells using adenoviral vectors combined with lipofection.

Science.gov (United States)

Buttgereit, P; Weineck, S; Röpke, G; Märten, A; Brand, K; Heinicke, T; Caselmann, W H; Huhn, D; Schmidt-Wolf, I G

2000-08-01

Tumor cells, such as lymphoma cells, are possible targets for gene therapy. In general, gene therapeutic approaches require efficient gene transfer to host cells and sufficient transgene expression. However, lymphoma cells previously have been demonstrated to be resistant to most of the currently available gene transfer methods. The aim of this study was to analyze various methods for transfection of lymphoma cells and to improve the efficiency of gene delivery. In accordance with previously published reports, lymphoma cells were demonstrated to be resistant to lipofection and electroporation. In contrast, we present an improved adenoviral protocol leading to highly efficient gene transfer to lymphoma cell lines derived from B cells as well as primary lymphoma cells being achieved with an adenoviral vector system encoding the beta-galactosidase protein. At a multiplicity of infection of 200, up to 100% of Daudi cells and Raji cells and 70% of OCI-Ly8-LAM53 cells could be transfected. Even at high adenoviral concentrations, no marked toxicity was observed, and the growth characteristics of the lymphoma cell lines were not impaired. The transfection rates in primary cells derived from six patients with non-Hodgkin's lymphoma were 30-65%, respectively. Transfection efficiency could be further increased by addition of cationic liposomes to adenoviral gene transfer. Furthermore, we examined the expression of the Coxsackie-adenoviral receptor (CAR) and the integrin receptors on the lymphoma cell surface. Flow cytometric analysis showed that 88% of Daudi cells, 69% of Raji cells, and 6% of OCI-Ly8-LAM53 cells expressed CAR on the cell surface. According to our data, adenoviral infection of lymphoma cells seems to be mediated by CAR. In contrast, integrin receptors are unlikely to play a major role, because lymphoma cells were negative for alphavbeta3-integrins and negative for alphavbeta5-integrins. In conclusion, this study demonstrates that B-lymphoma cell lines and

Ensuring Effective Mentoring in Tertiary Institutions in Anambra State ...

African Journals Online (AJOL)

This paper concerns itself only with ascertaining the strategies that could ensure effective mentoring in tertiary institutions. The survey method was employed. The study population comprised 78 teacher educators in tertiary institutions in Anambra State. One research question guided the study while one null hypothesis was ...

Quantitation of multisite EGF receptor phosphorylation using mass spectrometry and a novel normalization approach

DEFF Research Database (Denmark)

Erba, Elisabetta Boeri; Matthiesen, Rune; Bunkenborg, Jakob

2007-01-01

Using stable isotope labeling and mass spectrometry, we performed a sensitive, quantitative analysis of multiple phosphorylation sites of the epidermal growth factor (EGF) receptor. Phosphopeptide detection efficiency was significantly improved by using the tyrosine phosphatase inhibitor sodium p...

Scientific Research & Subsistence: Protocols to Ensure Co-Existence

Science.gov (United States)

Nachman, C.; Holman, A.; DeMaster, D.

2017-12-01

Commercial, industrial, and research interests in the Arctic are expanding rapidly. Potentials are numerous and exciting, giving rise to the need for guidelines to ensure interactions among waterway users do not conflict. Of particular concern is the potential for adverse impacts to U.S. Arctic coastal communities that rely on living marine resources for nutritional and cultural health, through subsistence hunts from small craft, ice edges, and shore. Recent events raised concerns over research surveys potentially interfering with subsistence hunts in the Bering, Chukchi, and Beaufort Seas. Incidents led to calls by Native Alaskan communities to restrict science activities with a mixed response from the scientific community (i.e., some sympathetic, some defensive). With a common goal of wanting to mitigate this potential interaction, Federal agencies made a commitment in the National Strategy for the Arctic Region to coordinate and consult with Alaska Natives and also to pursue responsible Arctic stewardship, with understanding through scientific research and traditional knowledge. The effort to create a "Standard of Care" for research surveys incorporates years of experience by subsistence hunters working to mitigate impacts of other anthropogenic activities in the region, as well as best practices by many in the research community. The protocols are designed to ensure potential conflicts between the scientific research community and subsistence hunters are avoided and to encourage mutual assistance and collaboration between researchers and hunters. The guidelines focus on enhancing communication between researchers and subsistence hunters before, during, and after research occurs. The best management practices outlined in the Standard of Care assist those overseeing and funding scientific research in making decisions about how best to accomplish the goals of the research while ensuring protection of the Alaska subsistence lifestyle. These protocols could also be

Partial Agonism of Taurine at Gamma-Containing Native and Recombinant GABAA Receptors

Science.gov (United States)

Kletke, Olaf; Gisselmann, Guenter; May, Andrea; Hatt, Hanns; A. Sergeeva, Olga

2013-01-01

Taurine is a semi-essential sulfonic acid found at high concentrations in plasma and mammalian tissues which regulates osmolarity, ion channel activity and glucose homeostasis. The structural requirements of GABAA-receptors (GABAAR) gated by taurine are not yet known. We determined taurine potency and efficacy relative to GABA at different types of recombinant GABAAR occurring in central histaminergic neurons of the mouse hypothalamic tuberomamillary nucleus (TMN) which controls arousal. At binary α1/2β1/3 receptors taurine was as efficient as GABA, whereas incorporation of the γ1/2 subunit reduced taurine efficacy to 60–90% of GABA. The mutation γ2F77I, which abolishes zolpidem potentiation, significantly reduced taurine efficacy at recombinant and native receptors compared to the wild type controls. As taurine was a full- or super- agonist at recombinant αxβ1δ-GABAAR, we generated a chimeric γ2 subunit carrying the δ subunit motif around F77 (MTVFLH). At α1/2β1γ2(MTVFLH) receptors taurine became a super-agonist, similar to δ-containing ternary receptors, but remained a partial agonist at β3-containing receptors. In conclusion, using site-directed mutagenesis we found structural determinants of taurine’s partial agonism at γ-containing GABAA receptors. Our study sheds new light on the β1 subunit conferring the widest range of taurine-efficacies modifying GABAAR function under (patho)physiological conditions. PMID:23637894

AmTAR2: Functional characterization of a honeybee tyramine receptor stimulating adenylyl cyclase activity.

Science.gov (United States)

Reim, Tina; Balfanz, Sabine; Baumann, Arnd; Blenau, Wolfgang; Thamm, Markus; Scheiner, Ricarda

2017-01-01

The biogenic monoamines norepinephrine and epinephrine regulate important physiological functions in vertebrates. Insects such as honeybees do not synthesize these neuroactive substances. Instead, they employ octopamine and tyramine for comparable physiological functions. These biogenic amines activate specific guanine nucleotide-binding (G) protein-coupled receptors (GPCRs). Based on pharmacological data obtained on heterologously expressed receptors, α- and β-adrenergic-like octopamine receptors are better activated by octopamine than by tyramine. Conversely, GPCRs forming the type 1 tyramine receptor clade (synonymous to octopamine/tyramine receptors) are better activated by tyramine than by octopamine. More recently, receptors were characterized which are almost exclusively activated by tyramine, thus forming an independent type 2 tyramine receptor clade. Functionally, type 1 tyramine receptors inhibit adenylyl cyclase activity, leading to a decrease in intracellular cAMP concentration ([cAMP] i ). Type 2 tyramine receptors can mediate Ca 2+ signals or both Ca 2+ signals and effects on [cAMP] i . We here provide evidence that the honeybee tyramine receptor 2 (AmTAR2), when heterologously expressed in flpTM cells, exclusively causes an increase in [cAMP] i . The receptor displays a pronounced preference for tyramine over octopamine. Its activity can be blocked by a series of established antagonists, of which mianserin and yohimbine are most efficient. The functional characterization of two tyramine receptors from the honeybee, AmTAR1 (previously named AmTYR1) and AmTAR2, which respond to tyramine by changing cAMP levels in opposite direction, is an important step towards understanding the actions of tyramine in honeybee behavior and physiology, particularly in comparison to the effects of octopamine. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ensuring capacity adequacy during energy transition in mature power markets: a social efficiency comparison of scarcity pricing and capacity mechanism

International Nuclear Information System (INIS)

Petitet, Marie; Finon, Dominique; Janssen, Tanguy

2016-01-01

This paper analyses how a capacity market mechanism can address security of supply objectives in the case of an energy transition scenario which combines both high energy efficiency efforts which stabilise demand in a context of mature markets and rapid increase of renewables share. The exogenous entry of variable renewables introduces a new challenge in matter of security of supply during peak hours. To analyse this situation, power markets are simulated on the long term with a model based on System Dynamics modelling which integrates both new investment and closure decisions. This last trait is an originality of the model which is very relevant to study market maturity. The addition of a capacity mechanism in a market architecture with price cap is compared to scarcity pricing in different situations. Simulations are performed for two different cases: a case without any exogenous closure of existing power plants and a case with exogenous retirements which create a need of new investments. Under the assumption of a risk-neutral investor, the results indicate that compared to an energy-only market with price cap set at euro 3,000/MWh, energy-only with scarcity pricing and capacity mechanism are two efficient market designs to reach an acceptable level of loss of load. Besides, the results highlight that the advantage of one design on the other in terms of social efficiency depends on the future scenarios which are simulated. Moreover, the results illustrates that the three market designs lead to different level of risk for peaking units, suggesting that including risk aversion is a relevant further step in the modelling. (authors)

Knowing your friends and foes--plant receptor-like kinases as initiators of symbiosis or defence.

Science.gov (United States)

Antolín-Llovera, Meritxell; Petutsching, Elena Kristin; Ried, Martina Katharina; Lipka, Volker; Nürnberger, Thorsten; Robatzek, Silke; Parniske, Martin

2014-12-01

The decision between defence and symbiosis signalling in plants involves alternative and modular plasma membrane-localized receptor complexes. A critical step in their activation is ligand-induced homo- or hetero-oligomerization of leucine-rich repeat (LRR)- and/or lysin motif (LysM) receptor-like kinases (RLKs). In defence signalling, receptor complexes form upon binding of pathogen-associated molecular patterns (PAMPs), including the bacterial flagellin-derived peptide flg22, or chitin. Similar mechanisms are likely to operate during the perception of microbial symbiont-derived (lipo)-chitooligosaccharides. The structurally related chitin-oligomer ligands chitooctaose and chitotetraose trigger defence and symbiosis signalling, respectively, and their discrimination involves closely related, if not identical, LysM-RLKs. This illustrates the demand for and the challenges imposed on decision mechanisms that ensure appropriate signal initiation. Appropriate signalling critically depends on abundance and localization of RLKs at the cell surface. This is regulated by internalization, which also provides a mechanism for the removal of activated signalling RLKs. Abundance of the malectin-like domain (MLD)-LRR-RLK Symbiosis Receptor-like Kinase (SYMRK) is additionally controlled by cleavage of its modular ectodomain, which generates a truncated and rapidly degraded RLK fragment. This review explores LRR- and LysM-mediated signalling, the involvement of MLD-LRR-RLKs in symbiosis and defence, and the role of endocytosis in RLK function. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

Purification and reconstitution of the calcium antagonist receptor of the voltage-sensitive calcium channel

International Nuclear Information System (INIS)

Curtis, B.M.

1986-01-01

Treatment with digitonin solubilized the calcium antagonist receptor as a stable complex with [ 3 H]nitrendipine from rat brain membranes. The solubilized complex retains allosteric coupling to binding sites for diltiazem, verapamil, and inorganic calcium antagonist sites. The calcium antagonist receptor from cardiac sarcolemma and the transverse-tubule membrane of skeletal muscle is also efficiently solubilized with digitonin and the receptor in all three tissues is a large glycoprotein with a sedimentation coefficient of 20 S. The T-tubule calcium antagonist receptor complex was extensively purified by a combination of chromatography on WGA-Sepharose, ion exchange chromatography, and sedimentation on sucrose gradients to yield preparations estimated to be 41% homogeneous by specific activity and 63% homogeneous by SDS gel electrophoresis. Analysis of SDS gels detect three polypeptides termed α(Mr 135,000), β(Mr 50,000), and γ(Mr 32,000) as noncovalently associated subunits of the calcium antagonist receptor. The α and γ subunits are glycosylated polypeptides, and the molecular weight of the core polypeptides are 108,000 and 24,000 respectively. The calcium antagonist receptor was reconstituted into a phospholipid bilayer by adding CHAPS and exogeneous lipid to the purified receptor followed by rapid detergent removal. This procedure resulted in the incorporation of 45% of the calcium antagonist receptor into closed phospholipid vesicles. Data suggests that the α, β, and γ subunits of the T-tubule calcium antagonist receptor are sufficient to form a functional calcium channel

Algorithm To Ensure And Enforce Brute-Force Attack-Resilient Password In Routers

OpenAIRE

Mohammed Farik; ABM Shawkat Ali

2015-01-01

Abstract Issues of weak login passwords arising from default passwords in wired and wireless routers has been a concern for more than a decade. In this research we develop and test an algorithm to ensure and enforce passwords in routers that are resistant to brute-force attack. A comparative analysis is performed to show the improved strengths of passwords derived via this algorithm. Implementation of this algorithm in routers will ensure setup of brute-force attack resistant passwords.

Problems of Ensuring Complex Business Security in the Conditions of Modern Globalization

OpenAIRE

Anatoliy Petrovich Sterkhov

2015-01-01

From the viewpoint of ensuring complex business security, the relevance of the present work is associated with the rationale of multilevel hierarchical approach to the classification of security threats in the age of globalization. The specificity of the threats specific to one or another level of the economy, helps to better understand and consequently to build an effective system of ensuring complex business security. For each of the nine hierarchical levels of the economy the author identi...

Determining Factors for Economic Efficiency in the Organic Olive Oil Sector

Directory of Open Access Journals (Sweden)

Enrique Bernal Jurado

2017-05-01

Full Text Available Spain looms large worldwide in organic olive oil production. However, this productive potential contrasts with the low internal consumption of the product. This situation makes Spain a world leader in its export. Companies in this sector have clear deficiencies, which must be corrected to ensure their survival over time. In this context, the aim of this study is to analyse the level of efficiency, in economic terms, of organic olive oil producers and to identify the factors explaining the best organizational practices. To do so, Data Envelopment Analysis (DEA and Qualitative Comparative Analysis (QCA have been used. The results reveal low levels of economic efficiency and the variables determining said efficiency.

The Theoretical Foundations of Formation of the Essence of Concept of «Ensuring the Economic Security of Enterprise in the Conditions of Raiding»

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Pysarevskyi Mykola I.

2017-05-01

Full Text Available The article is aimed at the scientific substantiation of the theoretical aspects of formation of an effective mechanism for ensuring the economic security of enterprise in the conditions of raiding. The conceptual approaches to determining the main features of individual elements of the conceptual apparatus, namely, the concepts of «economic security of enterprise» and «raiding» were analyzed. The author’s own definition of ensuring the economic security of enterprise in the conditions of raiding has been formed, which provides an opportunity to develop a complex of organizational and economic measures aimed at maintaining the sustainable functioning and development of enterprise in the current and future periods. Prospect for further research in this direction is a critical analysis of the approaches to assessing threats to the economic security of enterprise in the context of raiding, thus broadening the theoretical basis for an effective response mechanism and establishing a qualitative methodical basis for research. Application of new scientific and methodical approaches to the integrated assessment of the level of economic security in the conditions of raiding will ensure the development and implementation of efficient managerial decisions aimed at establishing a system of preventive measures to address threats to the economic security of enterprise.

Receptor saturation in roentgen films

Energy Technology Data Exchange (ETDEWEB)

Strid, K G; Reichmann, S [Sahlgrenska Sjukhuset, Goeteborg (Sweden)

1980-01-01

Roentgen-film recording of small object details of low attenuation differences (e.g. pulmonary vessels) is regularly seen to be impaired when the film is exposed to yield high values of optical density (D). This high-density failure is due to receptor saturation, which implies that at high exposure values most silver halide grains of the film are made developable, leaving few grains available to receive additional informative photons. The receptor saturation is analysed by means of a mathematical model of a non-screen film yielding Dsub(max) = 2.0. Optimum recording, defined by maximum signal-to-noise ratio in the image, is found at D approximately 0.64, corresponding to, on an average, 1.6 photons absorbed per grain. On the other hand, maximum contrast occurs at D approximately 1.4, where, on the average, 3.6 photons are absorbed per grain. The detective quantum efficiency of the film, i.e. the fraction of the photons actually contributing to the information content of the image, drops from 41 per cent at maximum signal-to-noise ratio to a mere 10 per cent at maximum contrast.

The Efficiency of Halal Processed Food Industry in Malaysia

Directory of Open Access Journals (Sweden)

Mohd Ali Mohd Noor

2016-06-01

Full Text Available Efficiency is indispensable for an industry to ensure cost reduction and profit maximization. It also helps the industry to be competitive and remain in the market. In 2010, Malaysia aims to be the world halal hub. The hub should capture at least five percent of the world halal market with at least 10,000 exporting firms. However the hub failed due to the small number of firms efficiency that finally contribute to less number of firms export. Thus, this study aimed to measure the efficiency of halal processed food industry in Malaysia using Data Envelopment Analysis (DEA. Input variables used were local raw inputs, labour, and monetary assets of halal food industry in Malaysia. Meanwhile the output used was the total sales revenue of the halal industry in Malaysia. The study shows that very few indusries are efficient in each category led by meat, dairy, cordials and juices, marine products, food crops, and grains industry. Therefore, the government needs to emphasize on industry’s efficiency to be competitive and be the world halal hub in the future.

MEASURES FOR A PRUDENTIAL EFFICIENCY SURVEILLANCE OF CREDIT INSTITUTIONS

Directory of Open Access Journals (Sweden)

Medar Lucian-Ion

2009-05-01

Full Text Available In this period of financial crisis, the efficiency and profitability of the banking sector received a strong blow and therefore, the banking prudence is a constant concern to all entities that comprise the European banking system. Major role in Romania of National Bank of Romania is to prevent systemic risk by promoting effective banking supervision, in order to ensure achievement of stability for entirely banking system.

Receptor oligomerization in family B1 of G-protein-coupled receptors

DEFF Research Database (Denmark)

Roed, Sarah Norklit; Ørgaard, Anne; Jørgensen, Rasmus

2012-01-01

, the glucagon receptor, and the receptors for parathyroid hormone (PTHR1 and PTHR2). The dysregulation of several family B1 receptors is involved in diseases, such as diabetes, chronic inflammation, and osteoporosis which underlines the pathophysiological importance of this GPCR subfamily. In spite of this......, investigation of family B1 receptor oligomerization and especially its pharmacological importance is still at an early stage. Even though GPCR oligomerization is a well-established phenomenon, there is a need for more investigations providing a direct link between these interactions and receptor functionality......The superfamily of the seven transmembrane G-protein-coupled receptors (7TM/GPCRs) is the largest family of membrane-associated receptors. GPCRs are involved in the pathophysiology of numerous human diseases, and they constitute an estimated 30-40% of all drug targets. During the last two decades...

Activation of glucocorticoid receptors increases 5-HT2A receptor levels

DEFF Research Database (Denmark)

Trajkovska, Viktorija; Kirkegaard, Lisbeth; Krey, Gesa

2009-01-01

an effect of GR activation on 5-HT2A levels, mature organotypic hippocampal cultures were exposed to corticosterone with or without GR antagonist mifepristone and mineralocorticoid receptor (MR) antagonist spironolactone. In GR under-expressing mice, hippocampal 5-HT2A receptor protein levels were decreased......Major depression is associated with both dysregulation of the hypothalamic pituitary adrenal axis and serotonergic deficiency, not the least of the 5-HT2A receptor. However, how these phenomena are linked to each other, and whether a low 5-HT2A receptor level is a state or a trait marker...... of depression is unknown. In mice with altered glucocorticoid receptor (GR) expression we investigated 5-HT2A receptor levels by Western blot and 3H-MDL100907 receptor binding. Serotonin fibre density was analyzed by stereological quantification of serotonin transporter immunopositive fibers. To establish...

Algorithm To Ensure And Enforce Brute-Force Attack-Resilient Password In Routers

Directory of Open Access Journals (Sweden)

Mohammed Farik

2015-08-01

Full Text Available Abstract Issues of weak login passwords arising from default passwords in wired and wireless routers has been a concern for more than a decade. In this research we develop and test an algorithm to ensure and enforce passwords in routers that are resistant to brute-force attack. A comparative analysis is performed to show the improved strengths of passwords derived via this algorithm. Implementation of this algorithm in routers will ensure setup of brute-force attack resistant passwords.

Influence analysis of sewage sludge methane fermentation parameters on process efficiency

OpenAIRE

Катерина Борисівна Сорокіна

2016-01-01

The efficiency dependence of sewage sludge organic matter decomposition from organization and conditions of the process is analyzed. Support of the optimal values of several parameters ensures to provide completeness of the sludge fermentation process and obtain biogas in calculated amount. Biogas utilization reduces costs for reactor heating and provides additional obtaining of other types of energy

THE ROLE OF THE LOCAL GOVERNMENT IN ENSURING THE ECONOMIC FREEDOM

Directory of Open Access Journals (Sweden)

Verginia Vedinaș

2013-11-01

Full Text Available The study aims to examine the role that local government plays in ensuring the economic freedom. It briefly examines the status of local authorities, deliberative and executive, and also the powers that they have to create the conditions for the exercise of economic freedom. The study also examines the constitutional regime of this fundamental freedom which is part of the rights and freedoms of the first generation. The purpose of the research aimed both identifying the role of local government in ensuring this basic freedom but also to determine possible means of action to be considered by the government within the territory.

Efficient relaxations for joint chance constrained AC optimal power flow

Energy Technology Data Exchange (ETDEWEB)

Baker, Kyri; Toomey, Bridget

2017-07-01

Evolving power systems with increasing levels of stochasticity call for a need to solve optimal power flow problems with large quantities of random variables. Weather forecasts, electricity prices, and shifting load patterns introduce higher levels of uncertainty and can yield optimization problems that are difficult to solve in an efficient manner. Solution methods for single chance constraints in optimal power flow problems have been considered in the literature, ensuring single constraints are satisfied with a prescribed probability; however, joint chance constraints, ensuring multiple constraints are simultaneously satisfied, have predominantly been solved via scenario-based approaches or by utilizing Boole's inequality as an upper bound. In this paper, joint chance constraints are used to solve an AC optimal power flow problem while preventing overvoltages in distribution grids under high penetrations of photovoltaic systems. A tighter version of Boole's inequality is derived and used to provide a new upper bound on the joint chance constraint, and simulation results are shown demonstrating the benefit of the proposed upper bound. The new framework allows for a less conservative and more computationally efficient solution to considering joint chance constraints, specifically regarding preventing overvoltages.

Discovering the Network Topology: An Efficient Approach for SDN

Directory of Open Access Journals (Sweden)

Leonardo OCHOA-ADAY

2016-11-01

Full Text Available Network topology is a physical description of the overall resources in the network. Collecting this information using efficient mechanisms becomes a critical task for important network functions such as routing, network management, quality of service (QoS, among many others. Recent technologies like Software-Defined Networks (SDN have emerged as promising approaches for managing the next generation networks. In order to ensure a proficient topology discovery service in SDN, we propose a simple agents-based mechanism. This mechanism improves the overall efficiency of the topology discovery process. In this paper, an algorithm for a novel Topology Discovery Protocol (SD-TDP is described. This protocol will be implemented in each switch through a software agent. Thus, this approach will provide a distributed solution to solve the problem of network topology discovery in a more simple and efficient way.

Analysis of hydrophobic interactions of antagonists with the beta2-adrenergic receptor.

Science.gov (United States)

Novoseletsky, V N; Pyrkov, T V; Efremov, R G

2010-01-01

The adrenergic receptors mediate a wide variety of physiological responses, including vasodilatation and vasoconstriction, heart rate modulation, and others. Beta-adrenergic antagonists ('beta-blockers') thus constitute a widely used class of drugs in cardiovascular medicine as well as in management of anxiety, migraine, and glaucoma. The importance of the hydrophobic effect has been evidenced for a wide range of beta-blocker properties. To better understand the role of the hydrophobic effect in recognition of beta-blockers by their receptor, we carried out a molecular docking study combined with an original approach to estimate receptor-ligand hydrophobic interactions. The proposed method is based on automatic detection of molecular fragments in ligands and the analysis of their interactions with receptors separately. A series of beta-blockers, based on phenylethanolamines and phenoxypropanolamines, were docked to the beta2-adrenoceptor binding site in the crystal structure. Hydrophobic complementarity between the ligand and the receptor was calculated using the PLATINUM web-server (http://model.nmr.ru/platinum). Based on the analysis of the hydrophobic match for molecular fragments of beta-blockers, we have developed a new scoring function which efficiently predicts dissociation constant (pKd) with strong correlations (r(2) approximately 0.8) with experimental data.

Study on Providing Professors with Efficient Service Based on Time Management Strategy

Science.gov (United States)

Li, Chunlin; Liu, Mengchao; Wang, Yining

2016-01-01

Time management is the study to use time scientifically by deploying skills, techniques and means, and maximizing time value to help individuals or organizations efficiently complete tasks and achieve goals. University professor as a body is an important force in teaching and research. In order to ensure high-quality teaching, productive research,…

Gβ promotes pheromone receptor polarization and yeast chemotropism by inhibiting receptor phosphorylation.

Science.gov (United States)

Ismael, Amber; Tian, Wei; Waszczak, Nicholas; Wang, Xin; Cao, Youfang; Suchkov, Dmitry; Bar, Eli; Metodiev, Metodi V; Liang, Jie; Arkowitz, Robert A; Stone, David E

2016-04-12

Gradient-directed cell migration (chemotaxis) and growth (chemotropism) are processes that are essential to the development and life cycles of all species. Cells use surface receptors to sense the shallow chemical gradients that elicit chemotaxis and chemotropism. Slight asymmetries in receptor activation are amplified by downstream signaling systems, which ultimately induce dynamic reorganization of the cytoskeleton. During the mating response of budding yeast, a model chemotropic system, the pheromone receptors on the plasma membrane polarize to the side of the cell closest to the stimulus. Although receptor polarization occurs before and independently of actin cable-dependent delivery of vesicles to the plasma membrane (directed secretion), it requires receptor internalization. Phosphorylation of pheromone receptors by yeast casein kinase 1 or 2 (Yck1/2) stimulates their internalization. We showed that the pheromone-responsive Gβγ dimer promotes the polarization of the pheromone receptor by interacting with Yck1/2 and locally inhibiting receptor phosphorylation. We also found that receptor phosphorylation is essential for chemotropism, independently of its role in inducing receptor internalization. A mathematical model supports the idea that the interaction between Gβγ and Yck1/2 results in differential phosphorylation and internalization of the pheromone receptor and accounts for its polarization before the initiation of directed secretion. Copyright © 2016, American Association for the Advancement of Science.

The Problem of Ensuring Reliability of Gas Turbine Engines

Science.gov (United States)

Nozhnitsky, Yu A.

2018-01-01

Requirements to advanced engines for civil aviation are discussing. Some significant problems of ensuring reliability of advanced gas turbine engines are mentioned. Special attention is paid to successful utilization of new materials and critical technologies. Also the problem of excluding failure of engine part due to low cycle or high cycle fatigue is discussing.

Real-time control strategy to maximize hybrid electric vehicle powertrain efficiency

International Nuclear Information System (INIS)

Shabbir, Wassif; Evangelou, Simos A.

2014-01-01

Highlights: • An off-line local control is proposed for real-time HEV energy management. • Powertrain efficiencies are studied to produce a unified objective function. • Penalty function is designed to ensure charge sustaining operation. • Implementation by storing optimal power share in a two-dimensional control map. • Proposed control improved fuel economy by up to 20% compared to conventional control. - Abstract: The proposed supervisory control system (SCS) uses a control map to maximize the powertrain efficiency of a hybrid electric vehicle (HEV) in real-time. The paper presents the methodology and structure of the control, including a novel, comprehensive and unified expression for the overall powertrain efficiency that considers the engine-generator set and the battery in depth as well as the power electronics. A control map is then produced with instructions for the optimal power share between the engine branch and battery branch of the vehicle such that the powertrain efficiency is maximized. This map is computed off-line and can thereafter be operated in real-time at very low computational cost. A charge sustaining factor is also developed and introduced to ensure the SCS operates the vehicle within desired SOC bounds. This SCS is then tested and benchmarked against two conventional control strategies in a high-fidelity vehicle model, representing a series HEV. Extensive simulation results are presented for repeated cycles of a diverse range of standard driving cycles, showing significant improvements in fuel economy (up to 20%) and less aggressive use of the battery

Robust and efficient parameter estimation in dynamic models of biological systems.

Science.gov (United States)

Gábor, Attila; Banga, Julio R

2015-10-29

Dynamic modelling provides a systematic framework to understand function in biological systems. Parameter estimation in nonlinear dynamic models remains a very challenging inverse problem due to its nonconvexity and ill-conditioning. Associated issues like overfitting and local solutions are usually not properly addressed in the systems biology literature despite their importance. Here we present a method for robust and efficient parameter estimation which uses two main strategies to surmount the aforementioned difficulties: (i) efficient global optimization to deal with nonconvexity, and (ii) proper regularization methods to handle ill-conditioning. In the case of regularization, we present a detailed critical comparison of methods and guidelines for properly tuning them. Further, we show how regularized estimations ensure the best trade-offs between bias and variance, reducing overfitting, and allowing the incorporation of prior knowledge in a systematic way. We illustrate the performance of the presented method with seven case studies of different nature and increasing complexity, considering several scenarios of data availability, measurement noise and prior knowledge. We show how our method ensures improved estimations with faster and more stable convergence. We also show how the calibrated models are more generalizable. Finally, we give a set of simple guidelines to apply this strategy to a wide variety of calibration problems. Here we provide a parameter estimation strategy which combines efficient global optimization with a regularization scheme. This method is able to calibrate dynamic models in an efficient and robust way, effectively fighting overfitting and allowing the incorporation of prior information.

Glucocorticoid receptor modulators.

Science.gov (United States)

Meijer, Onno C; Koorneef, Lisa L; Kroon, Jan

2018-06-01

The glucocorticoid hormone cortisol acts throughout the body to support circadian processes and adaptation to stress. The glucocorticoid receptor is the target of cortisol and of synthetic glucocorticoids, which are used widely in the clinic. Both agonism and antagonism of the glucocorticoid receptor may be beneficial in disease, but given the wide expression of the receptor and involvement in various processes, beneficial effects are often accompanied by unwanted side effects. Selective glucocorticoid receptor modulators are ligands that induce a receptor conformation that allows activation of only a subset of downstream signaling pathways. Such molecules thereby combine agonistic and antagonistic properties. Here we discuss the mechanisms underlying selective receptor modulation and their promise in treating diseases in several organ systems where cortisol signaling plays a role. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Diesel engine power generating set efficiency for nuclear power plant electrical energy supply in case of emergency

International Nuclear Information System (INIS)

Popovic, I.; Aksamija, R.; Tumpa, M.

1984-01-01

Working ability of diesel engine set to starting and functioning reliability during operation is evaluated within study of efficiency. methods of calculation are applied: data compilation method and Markov method. The evaluation is that a diesel engine set has efficiency of 0.993285. It is a high efficiency which ensures a safe start, load take over and safe operation. This evaluation makes a basis for similar calculations which will be needed for national nuclear program. (author)

28 CFR 97.20 - Standards to ensure the safety of violent prisoners during transport.

Science.gov (United States)

2010-07-01

... physical safety of the prisoners during transport, including a first-aid kit and employees who are... transportation, where practicable; (f) Policies, practices, and procedures are in effect to ensure that female..., practices, and procedures are in effect to ensure that female guards are on duty to supervise the...

Development of Beet Sugar Production in Ryazan Region in the Context of Ensuring Food Security

Directory of Open Access Journals (Sweden)

Mansurov Ruslan Evgenyevich

2014-12-01

Full Text Available The article presents the results of the research on the current state of the beet sugar subcomplex of Ryazan region in the context of the need of improving its efficiency. The study let the author determine that currently the beet sugar subcomplex of Ryazan region does not ensure domestic demand in sand sugar. However, there are reserves of providing more efficient use of soil and climate capacity as well as the productivity potential of the region. When applying the technology of field beet piling, the period of sugar production at sugar factories may be extended up to 200 days. At this, up to 51 thousand tons of sand sugar can be produced. This amount will completely cover the annual demand for sugar in Ryazan region. In order to further study the feasibility of this approach, zoning was carried out and let allocate the zones of beet seeding. As a result, it was determined that a number of areas are far removed from the place of treatment, and in terms of transportation costs minimization the sugar beet cultivation in these areas is not rational. As an alternative, the author proposes to consider the possibility of building a new sugar factory in Ryazhsky district with the processing capacity of 1,000 tons of sugar beet per day. Taking this into account, the recommended acreage of sugar beet by districts and zones of raw material supply were obtained through corresponding calculations.

An efficient targeted drug delivery through apotransferrin loaded nanoparticles.

Directory of Open Access Journals (Sweden)

Athuluri Divakar Sai Krishna

Full Text Available BACKGROUND: Cancerous state is a highly stimulated environment of metabolically active cells. The cells under these conditions over express selective receptors for assimilation of factors essential for growth and transformation. Such receptors would serve as potential targets for the specific ligand mediated transport of pharmaceutically active molecules. The present study demonstrates the specificity and efficacy of protein nanoparticle of apotransferrin for targeted delivery of doxorubicin. METHODOLOGY/PRINCIPAL FINDINGS: Apotransferrin nanoparticles were developed by sol-oil chemistry. A comparative analysis of efficiency of drug delivery in conjugated and non-conjugated forms of doxorubicin to apotransferrin nanoparticle is presented. The spherical shaped apotransferrin nanoparticles (nano have diameters of 25-50 etam, which increase to 60-80 etam upon direct loading of drug (direct-nano, and showed further increase in dimension (75-95 etam in conjugated nanoparticles (conj-nano. The competitive experiments with the transferrin receptor specific antibody showed the entry of both conj-nano and direct-nano into the cells through transferrin receptor mediated endocytosis. Results of various studies conducted clearly establish the superiority of the direct-nano over conj-nano viz. (a localization studies showed complete release of drug very early, even as early as 30 min after treatment, with the drug localizing in the target organelle (nucleus (b pharmacokinetic studies showed enhanced drug concentrations, in circulation with sustainable half-life (c the studies also demonstrated efficient drug delivery, and an enhanced inhibition of proliferation in cancer cells. Tissue distribution analysis showed intravenous administration of direct nano lead to higher drug localization in liver, and blood as compared to relatively lesser localization in heart, kidney and spleen. Experiments using rat cancer model confirmed the efficacy of the formulation in

Reserch on energy absorption efficiency in full-duplex multi-user broadcast channel

Directory of Open Access Journals (Sweden)

JIANG Fengju

2015-02-01

Full Text Available This paper studies the user energy scenarios absorption efficiency optimization in multiuser broadcast channel.This paper assumed that the user terminals using full-duplex mode that the user receive uplink energy information and transfer uplink energy at the same time.In this paper,we maximize the minimum user uplink transmit power,when we ensure that each user′s energy absorption efficiency is greater than a threshold value and satisfies the premise of the base station downlink power emission limits.Finally,the simulation results confirm the effectiveness of the proposed algorithm.

Identification of a Novel Recycling Sequence in the C-tail of FPR2/ALX Receptor

Science.gov (United States)

Thompson, Dawn; McArthur, Simon; Hislop, James N.; Flower, Roderick J.; Perretti, Mauro

2014-01-01

Formyl-peptide receptor type 2 (FPR2; also called ALX because it is the receptor for lipoxin A4) sustains a variety of biological responses relevant to the development and control of inflammation, yet the cellular regulation of this G-protein-coupled receptor remains unexplored. Here we report that, in response to peptide agonist activation, FPR2/ALX undergoes β-arrestin-mediated endocytosis followed by rapid recycling to the plasma membrane. We identify a transplantable recycling sequence that is both necessary and sufficient for efficient receptor recycling. Furthermore, removal of this C-terminal recycling sequence alters the endocytic fate of FPR2/ALX and evokes pro-apoptotic effects in response to agonist activation. This study demonstrates the importance of endocytic recycling in the anti-apoptotic properties of FPR2/ALX and identifies the molecular determinant required for modulation of this process fundamental for the control of inflammation. PMID:25326384

Angiotensin type 2 receptor (AT2R) and receptor Mas

DEFF Research Database (Denmark)

Villela, Daniel; Leonhardt, Julia; Patel, Neal

2015-01-01

The angiotensin type 2 receptor (AT2R) and the receptor Mas are components of the protective arms of the renin-angiotensin system (RAS), i.e. they both mediate tissue protective and regenerative actions. The spectrum of actions of these two receptors and their signalling mechanisms display striki...

Enhancement of polymeric immunoglobulin receptor transcytosis by biparatopic VHH.

Directory of Open Access Journals (Sweden)

Chris D Emmerson

Full Text Available The polymeric immunoglobulin receptor (pIgR ensures the transport of dimeric immunoglobulin A (dIgA and pentameric immunoglobulin M (pIgM across epithelia to the mucosal layer of for example the intestines and the lungs via transcytosis. Per day the human pIgR mediates the excretion of 2 to 5 grams of dIgA into the mucosa of luminal organs. This system could prove useful for therapies aiming at excretion of compounds into the mucosa. Here we investigated the use of the variable domain of camelid derived heavy chain only antibodies, also known as VHHs or Nanobodies®, targeting the human pIgR, as a transport system across epithelial cells. We show that VHHs directed against the human pIgR are able to bind the receptor with high affinity (∼1 nM and that they compete with the natural ligand, dIgA. In a transcytosis assay both native and phage-bound VHH were only able to get across polarized MDCK cells that express the human pIgR gene in a basolateral to apical fashion. Indicating that the VHHs are able to translocate across epithelia and to take along large particles of cargo. Furthermore, by making multivalent VHHs we were able to enhance the transport of the compounds both in a MDCK-hpIgR and Caco-2 cell system, probably by inducing receptor clustering. These results show that VHHs can be used as a carrier system to exploit the human pIgR transcytotic system and that multivalent compounds are able to significantly enhance the transport across epithelial monolayers.

ANALYSIS OF THE ENERGY EFFICIENCY OF PHOTOVOLTAIC POLYCRYSTALLINE AND THIN-FILM PHOTOVOLTAIC FARM IN THE DOLINA ZIELAWY

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Piotr Dragan

2016-12-01

Full Text Available Renewable energy is an opportunity not only to improve the energy efficiency of individual customers, but also to ensure energy security for local governments. In 2007, in Lublin province 5 municipalities have formed a partnership government called "Valley of Zielawa". The objectives of the partnership is the cooperation in the field of education, tasks in the field of culture, health protection, social welfare, fire protection and street lighting. One of the overarching goals of the partnership include ensure energy security and improving energy efficiency through the utilization of solar energy. Solar energy resources in the Lublin region are mainly characterized by a very high degree of sunlight compared to other regions of the country. The greatest potential for solar energy use is the eastern area of the province (including the area of partnership. In order to ensure the energy security of the community established a company Energy Valley of Zielawa, which in 2014 built a photovoltaic farm with a capacity of 1.4 MW in the Bordziłówka in Municipality Rossosz. This paper presents an analysis of photovoltaic farm work over the year and a half and the analysis of the energy efficiency of various types of photovoltaic panels which produce energy on a farm in photovoltaic Bordziłówce.

Patient-specific dosimetry in peptide receptor radionuclide therapy: a clinical review

International Nuclear Information System (INIS)

Chalkia, M.T.; Stefanoyiannis, A.P.; Chatziioannou, S.N.; Efstathopoulos, E.P.; Round, W.H.; Nikiforidis, G.C.

2015-01-01

Neuroendocrine tumours (NETs) belong to a relatively rare class of neoplasms. Nonetheless, their prevalence has increased significantly during the last decades. Peptide receptor radionuclide therapy (PRRT) is a relatively new treatment approach for inoperable or metastasised NETs. The therapeutic effect is based on the binding of radiolabelled somatostatin analogue peptides with NETs’ somatostatin receptors, resulting in internal irradiation of tumours. Pre-therapeutic patient-specific dosimetry is essential to ensure that a treatment course has high levels of safety and efficacy. This paper reviews the methods applied for PRRT dosimetry, as well as the dosimetric results presented in the literature. Focus is given on data concerning the therapeutic somatostatin analogue radiopeptides 111 In-[DTPA o , D -Phe 1 ]-octreotide ( 111 In-DTPA-octreotide), 90 Y-[DOTA o ,Tyr 3 ]-octreotide ( 90 Y-DOTATOC) and 177 Lu-[DOTA o ,Tyr 3 ,Thr 8 ]-octreotide ( 177 Lu-DOTATATE). Following the Medical Internal Radiation Dose (MIRD) Committee formalism, dosimetric analysis demonstrates large interpatient variability in tumour and organ uptake, with kidneys and bone marrow being the critical organs. The results are dependent on the image acquisition and processing protocol, as well as the dosimetric imaging radiopharmaceutical.

Calix[4]arenes Containing a Ureido Functionality on the Lower Rim as Highly Efficient Receptors for Anion Recognition.

Czech Academy of Sciences Publication Activity Database

Klejch, T.; Slavíček, J.; Hudeček, O.; Eigner, V.; Gutierrez, Natalia Andrea; Cuřínová, Petra; Lhoták, P.

2016-01-01

Roč. 40, č. 9 (2016), s. 7935-7942 ISSN 1144-0546 Institutional support: RVO:67985858 Keywords : calix[4]arene * anion recognition * receptors Subject RIV: CC - Organic Chemistry Impact factor: 3.269, year: 2016

The ERECTA gene regulates plant transpiration efficiency in Arabidopsis.

Science.gov (United States)

Masle, Josette; Gilmore, Scott R; Farquhar, Graham D

2005-08-11

Assimilation of carbon by plants incurs water costs. In the many parts of the world where water is in short supply, plant transpiration efficiency, the ratio of carbon fixation to water loss, is critical to plant survival, crop yield and vegetation dynamics. When challenged by variations in their environment, plants often seem to coordinate photosynthesis and transpiration, but significant genetic variation in transpiration efficiency has been identified both between and within species. This has allowed plant breeders to develop effective selection programmes for the improved transpiration efficiency of crops, after it was demonstrated that carbon isotopic discrimination, Delta, of plant matter was a reliable and sensitive marker negatively related to variation in transpiration efficiency. However, little is known of the genetic controls of transpiration efficiency. Here we report the isolation of a gene that regulates transpiration efficiency, ERECTA. We show that ERECTA, a putative leucine-rich repeat receptor-like kinase (LRR-RLK) known for its effects on inflorescence development, is a major contributor to a locus for Delta on Arabidopsis chromosome 2. Mechanisms include, but are not limited to, effects on stomatal density, epidermal cell expansion, mesophyll cell proliferation and cell-cell contact.

T-cell receptor transfer into human T cells with ecotropic retroviral vectors.

Science.gov (United States)

Koste, L; Beissert, T; Hoff, H; Pretsch, L; Türeci, Ö; Sahin, U

2014-05-01

Adoptive T-cell transfer for cancer immunotherapy requires genetic modification of T cells with recombinant T-cell receptors (TCRs). Amphotropic retroviral vectors (RVs) used for TCR transduction for this purpose are considered safe in principle. Despite this, TCR-coding and packaging vectors could theoretically recombine to produce replication competent vectors (RCVs), and transduced T-cell preparations must be proven free of RCV. To eliminate the need for RCV testing, we transduced human T cells with ecotropic RVs so potential RCV would be non-infectious for human cells. We show that transfection of synthetic messenger RNA encoding murine cationic amino-acid transporter 1 (mCAT-1), the receptor for murine retroviruses, enables efficient transient ecotropic transduction of human T cells. mCAT-1-dependent transduction was more efficient than amphotropic transduction performed in parallel, and preferentially targeted naive T cells. Moreover, we demonstrate that ecotropic TCR transduction results in antigen-specific restimulation of primary human T cells. Thus, ecotropic RVs represent a versatile, safe and potent tool to prepare T cells for the adoptive transfer.

Influence analysis of sewage sludge methane fermentation parameters on process efficiency

Directory of Open Access Journals (Sweden)

Катерина Борисівна Сорокіна

2016-12-01

Full Text Available The efficiency dependence of sewage sludge organic matter decomposition from organization and conditions of the process is analyzed. Support of the optimal values of several parameters ensures to provide completeness of the sludge fermentation process and obtain biogas in calculated amount. Biogas utilization reduces costs for reactor heating and provides additional obtaining of other types of energy

A search for presynaptic inhibitory histamine receptors in guinea-pig tissues: Further H3 receptors but no evidence for H4 receptors.

Science.gov (United States)

Petri, Doris; Schlicker, Eberhard

2016-07-01

The histamine H4 receptor is coupled to Gi/o proteins and expressed on inflammatory cells and lymphoid tissues; it was suggested that this receptor also occurs in the brain or on peripheral neurones. Since many Gi/o protein-coupled receptors, including the H3 receptor, serve as presynaptic inhibitory receptors, we studied whether the sympathetic neurones supplying four peripheral tissues and the cholinergic neurones in the hippocampus from the guinea-pig are equipped with release-modulating H4 and H3 receptors. For this purpose, we preincubated tissue pieces from the aorta, atrium, renal cortex and vas deferens with (3)H-noradrenaline and hippocampal slices with (3)H-choline and determined the electrically evoked tritium overflow. The stimulation-evoked overflow in the five superfused tissues was inhibited by the muscarinic receptor agonist oxotremorine, which served as a positive control, but not affected by the H4 receptor agonist 4-methylhistamine. The H3 receptor agonist R-α-methylhistamine inhibited noradrenaline release in the peripheral tissues without affecting acetylcholine release in the hippocampal slices. Thioperamide shifted the concentration-response curve of histamine in the aorta and the renal cortex to the right, yielding apparent pA2 values of 8.0 and 8.1, respectively, which are close to its affinity at other H3 receptors but higher by one log unit than its pKi at the H4 receptor of the guinea-pig. In conclusion, histamine H4 receptors could not be identified in five experimental models of the guinea-pig that are suited for the detection of presynaptic inhibitory receptors whereas H3 receptors could be shown in the peripheral tissues but not in the hippocampus. This article is part of the Special Issue entitled 'Histamine Receptors'. Copyright © 2015 Elsevier Ltd. All rights reserved.

Exploring the existence of Kuznets curve in countries' environmental efficiency using DEA window analysis

International Nuclear Information System (INIS)

Halkos, George Emm.; Tzeremes, Nickolaos G.

2009-01-01

This paper, using data envelopment (DEA) window analysis and generalized method of moments (GMM) estimators, examines the existence of a Kuznets type relationship between countries' environmental efficiency and national income. Specifically, it measures the environmental efficiency of 17 OECD countries by constructing environmental efficiency ratios for the time period 1980-2002. The analysis with the application of dynamic panel data reveals that there isn't a Kuznets type relationship between environmental efficiency and income. Allowing for dynamic effects we find that the adjustment to the target ratio is instantaneous. We also find that increased economic activity does not always ensure environmental protection and thus the path of growth is important in addition to the growth itself. (author)

Innovations as a Factor for Ensuring Economic Safety

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Maxim SANDU

2017-06-01

Full Text Available In modern conditions of development of the competitive environment, one of the main ways to solve economic, social and environmental problems is to use the latest achievements of science and technology. Each enterprise seeks to ensure that economic growth is intense, i.e. to be a consequence of the application of more sophisticated factors of production and technology. The prerequisite for intensive growth is the use of innovative strategy in the practical activities of enterprises. The end result of innovations is the materialization and industrial development of innovation, the idea of which can be the scientific and technical activity, and marketing research to identify unmet needs. The innovations are an effective defensive reaction of the firm to the emerging threats of losing market place, constant pressure from competitors, the challenge of new technologies, shortening the life of products, legislative restrictions and changing the market situation. In the offensive version, the innovation is a mean of exploiting new opportunities to preserve or gain a competitive advantage. In the long term aspect, the company has no choice but to pursue an innovation policy, which is the only source of lasting success. The main objective of researching the innovation activity of any organization is to ensure competitiveness in market conditions in order to identify risk factors and ways to overcome them.

Ensuring the Validity of the Micro Foundation in DSGE Models

DEFF Research Database (Denmark)

Andreasen, Martin Møller

& Primiceri (American Economic Review, forth- coming) and Fernández-Villaverde & Rubio-Ramírez (Review of Economic Studies, 2007) do not satisfy these sufficient conditions, or any other known set of conditions ensuring finite values for the objective functions. Thus, the validity of the micro foundation......The presence of i) stochastic trends, ii) deterministic trends, and/or iii) stochastic volatil- ity in DSGE models may imply that the agents' objective functions attain infinite values. We say that such models do not have a valid micro foundation. The paper derives sufficient condi- tions which...... ensure that the objective functions of the households and the firms are finite even when various trends and stochastic volatility are included in a standard DSGE model. Based on these conditions we test the validity of the micro foundation in six DSGE models from the literature. The models of Justiniano...

Efficient Prediction of Progesterone Receptor Interactome Using a Support Vector Machine Model

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Ji-Long Liu

2015-03-01

Full Text Available Protein-protein interaction (PPI is essential for almost all cellular processes and identification of PPI is a crucial task for biomedical researchers. So far, most computational studies of PPI are intended for pair-wise prediction. Theoretically, predicting protein partners for a single protein is likely a simpler problem. Given enough data for a particular protein, the results can be more accurate than general PPI predictors. In the present study, we assessed the potential of using the support vector machine (SVM model with selected features centered on a particular protein for PPI prediction. As a proof-of-concept study, we applied this method to identify the interactome of progesterone receptor (PR, a protein which is essential for coordinating female reproduction in mammals by mediating the actions of ovarian progesterone. We achieved an accuracy of 91.9%, sensitivity of 92.8% and specificity of 91.2%. Our method is generally applicable to any other proteins and therefore may be of help in guiding biomedical experiments.

Real-Time G-Protein-Coupled Receptor Imaging to Understand and Quantify Receptor Dynamics

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María S. Aymerich

2011-01-01

Full Text Available Understanding the trafficking of G-protein-coupled receptors (GPCRs and their regulation by agonists and antagonists is fundamental to develop more effective drugs. Optical methods using fluorescent-tagged receptors and spinning disk confocal microscopy are useful tools to investigate membrane receptor dynamics in living cells. The aim of this study was to develop a method to characterize receptor dynamics using this system which offers the advantage of very fast image acquisition with minimal cell perturbation. However, in short-term assays photobleaching was still a problem. Thus, we developed a procedure to perform a photobleaching-corrected image analysis. A study of short-term dynamics of the long isoform of the dopamine type 2 receptor revealed an agonist-induced increase in the mobile fraction of receptors with a rate of movement of 0.08 μm/s For long-term assays, the ratio between the relative fluorescence intensity at the cell surface versus that in the intracellular compartment indicated that receptor internalization only occurred in cells co-expressing G protein-coupled receptor kinase 2. These results indicate that the lateral movement of receptors and receptor internalization are not directly coupled. Thus, we believe that live imaging of GPCRs using spinning disk confocal image analysis constitutes a powerful tool to study of receptor dynamics.

Accurate and efficient gp120 V3 loop structure based models for the determination of HIV-1 co-receptor usage

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Vaisman Iosif I

2010-10-01

Full Text Available Abstract Background HIV-1 targets human cells expressing both the CD4 receptor, which binds the viral envelope glycoprotein gp120, as well as either the CCR5 (R5 or CXCR4 (X4 co-receptors, which interact primarily with the third hypervariable loop (V3 loop of gp120. Determination of HIV-1 affinity for either the R5 or X4 co-receptor on host cells facilitates the inclusion of co-receptor antagonists as a part of patient treatment strategies. A dataset of 1193 distinct gp120 V3 loop peptide sequences (989 R5-utilizing, 204 X4-capable is utilized to train predictive classifiers based on implementations of random forest, support vector machine, boosted decision tree, and neural network machine learning algorithms. An in silico mutagenesis procedure employing multibody statistical potentials, computational geometry, and threading of variant V3 sequences onto an experimental structure, is used to generate a feature vector representation for each variant whose components measure environmental perturbations at corresponding structural positions. Results Classifier performance is evaluated based on stratified 10-fold cross-validation, stratified dataset splits (2/3 training, 1/3 validation, and leave-one-out cross-validation. Best reported values of sensitivity (85%, specificity (100%, and precision (98% for predicting X4-capable HIV-1 virus, overall accuracy (97%, Matthew's correlation coefficient (89%, balanced error rate (0.08, and ROC area (0.97 all reach critical thresholds, suggesting that the models outperform six other state-of-the-art methods and come closer to competing with phenotype assays. Conclusions The trained classifiers provide instantaneous and reliable predictions regarding HIV-1 co-receptor usage, requiring only translated V3 loop genotypes as input. Furthermore, the novelty of these computational mutagenesis based predictor attributes distinguishes the models as orthogonal and complementary to previous methods that utilize sequence

Promiscuous RNA binding ensures effective encapsidation of APOBEC3 proteins by HIV-1.

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Luis Apolonia

2015-01-01

Full Text Available The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3 proteins are cell-encoded cytidine deaminases, some of which, such as APOBEC3G (A3G and APOBEC3F (A3F, act as potent human immunodeficiency virus type-1 (HIV-1 restriction factors. These proteins require packaging into HIV-1 particles to exert their antiviral activities, but the molecular mechanism by which this occurs is incompletely understood. The nucleocapsid (NC region of HIV-1 Gag is required for efficient incorporation of A3G and A3F, and the interaction between A3G and NC has previously been shown to be RNA-dependent. Here, we address this issue in detail by first determining which RNAs are able to bind to A3G and A3F in HV-1 infected cells, as well as in cell-free virions, using the unbiased individual-nucleotide resolution UV cross-linking and immunoprecipitation (iCLIP method. We show that A3G and A3F bind many different types of RNA, including HIV-1 RNA, cellular mRNAs and small non-coding RNAs such as the Y or 7SL RNAs. Interestingly, A3G/F incorporation is unaffected when the levels of packaged HIV-1 genomic RNA (gRNA and 7SL RNA are reduced, implying that these RNAs are not essential for efficient A3G/F packaging. Confirming earlier work, HIV-1 particles formed with Gag lacking the NC domain (Gag ΔNC fail to encapsidate A3G/F. Here, we exploit this system by demonstrating that the addition of an assortment of heterologous RNA-binding proteins and domains to Gag ΔNC efficiently restored A3G/F packaging, indicating that A3G and A3F have the ability to engage multiple RNAs to ensure viral encapsidation. We propose that the rather indiscriminate RNA binding characteristics of A3G and A3F promote functionality by enabling recruitment into a wide range of retroviral particles whose packaged RNA genomes comprise divergent sequences.

Knock-In Mice with NOP-eGFP Receptors Identify Receptor Cellular and Regional Localization.

Science.gov (United States)

Ozawa, Akihiko; Brunori, Gloria; Mercatelli, Daniela; Wu, Jinhua; Cippitelli, Andrea; Zou, Bende; Xie, Xinmin Simon; Williams, Melissa; Zaveri, Nurulain T; Low, Sarah; Scherrer, Grégory; Kieffer, Brigitte L; Toll, Lawrence

2015-08-19

The nociceptin/orphanin FQ (NOP) receptor, the fourth member of the opioid receptor family, is involved in many processes common to the opioid receptors including pain and drug abuse. To better characterize receptor location and trafficking, knock-in mice were created by inserting the gene encoding enhanced green fluorescent protein (eGFP) into the NOP receptor gene (Oprl1) and producing mice expressing a functional NOP-eGFP C-terminal fusion in place of the native NOP receptor. The NOP-eGFP receptor was present in brain of homozygous knock-in animals in concentrations somewhat higher than in wild-type mice and was functional when tested for stimulation of [(35)S]GTPγS binding in vitro and in patch-clamp electrophysiology in dorsal root ganglia (DRG) neurons and hippocampal slices. Inhibition of morphine analgesia was equivalent when tested in knock-in and wild-type mice. Imaging revealed detailed neuroanatomy in brain, spinal cord, and DRG and was generally consistent with in vitro autoradiographic imaging of receptor location. Multicolor immunohistochemistry identified cells coexpressing various spinal cord and DRG cellular markers, as well as coexpression with μ-opioid receptors in DRG and brain regions. Both in tissue slices and primary cultures, the NOP-eGFP receptors appear throughout the cell body and in processes. These knock-in mice have NOP receptors that function both in vitro and in vivo and appear to be an exceptional tool to study receptor neuroanatomy and correlate with NOP receptor function. The NOP receptor, the fourth member of the opioid receptor family, is involved in pain, drug abuse, and a number of other CNS processes. The regional and cellular distribution has been difficult to determine due to lack of validated antibodies for immunohistochemical analysis. To provide a new tool for the investigation of receptor localization, we have produced knock-in mice with a fluorescent-tagged NOP receptor in place of the native NOP receptor. These

Distinct Prion Domain Sequences Ensure Efficient Amyloid Propagation by Promoting Chaperone Binding or Processing In Vivo.

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Christine R Langlois

2016-11-01

Full Text Available Prions are a group of proteins that can adopt a spectrum of metastable conformations in vivo. These alternative states change protein function and are self-replicating and transmissible, creating protein-based elements of inheritance and infectivity. Prion conformational flexibility is encoded in the amino acid composition and sequence of the protein, which dictate its ability not only to form an ordered aggregate known as amyloid but also to maintain and transmit this structure in vivo. But, while we can effectively predict amyloid propensity in vitro, the mechanism by which sequence elements promote prion propagation in vivo remains unclear. In yeast, propagation of the [PSI+] prion, the amyloid form of the Sup35 protein, has been linked to an oligopeptide repeat region of the protein. Here, we demonstrate that this region is composed of separable functional elements, the repeats themselves and a repeat proximal region, which are both required for efficient prion propagation. Changes in the numbers of these elements do not alter the physical properties of Sup35 amyloid, but their presence promotes amyloid fragmentation, and therefore maintenance, by molecular chaperones. Rather than acting redundantly, our observations suggest that these sequence elements make complementary contributions to prion propagation, with the repeat proximal region promoting chaperone binding to and the repeats promoting chaperone processing of Sup35 amyloid.

Receptor assay

Energy Technology Data Exchange (ETDEWEB)

Kato, K; Ibayashi, H [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

1975-05-01

This paper summarized present status and problems of analysis of hormone receptor and a few considerations on clinical significance of receptor abnormalities. It was pointed that in future clinical field quantitative and qualitative analysis of receptor did not remain only in the etiological discussion, but that it was an epoch-making field of investigation which contained the possiblity of artificial change of sensitivity of living body on drugs and the development connected directly with treatment of various diseases.

Dominant integration locus drives continuous diversification of plant immune receptors with exogenous domain fusions.

Science.gov (United States)

Bailey, Paul C; Schudoma, Christian; Jackson, William; Baggs, Erin; Dagdas, Gulay; Haerty, Wilfried; Moscou, Matthew; Krasileva, Ksenia V

2018-02-19

The plant immune system is innate and encoded in the germline. Using it efficiently, plants are capable of recognizing a diverse range of rapidly evolving pathogens. A recently described phenomenon shows that plant immune receptors are able to recognize pathogen effectors through the acquisition of exogenous protein domains from other plant genes. We show that plant immune receptors with integrated domains are distributed unevenly across their phylogeny in grasses. Using phylogenetic analysis, we uncover a major integration clade, whose members underwent repeated independent integration events producing diverse fusions. This clade is ancestral in grasses with members often found on syntenic chromosomes. Analyses of these fusion events reveals that homologous receptors can be fused to diverse domains. Furthermore, we discover a 43 amino acid long motif associated with this dominant integration clade which is located immediately upstream of the fusion site. Sequence analysis reveals that DNA transposition and/or ectopic recombination are the most likely mechanisms of formation for nucleotide binding leucine rich repeat proteins with integrated domains. The identification of this subclass of plant immune receptors that is naturally adapted to new domain integration will inform biotechnological approaches for generating synthetic receptors with novel pathogen "baits."

Good Work Ensures Employment Success. Myths and Realities No. 2.

Science.gov (United States)

Brown, Bettina Lankard

It is a myth that skills alone ensure employment. Other keys to workplace success include continuous learning, emotional intelligence, networking, flexibility, and commitment to business objectives. Although academic degrees, skill certifications, and other documentation of accomplishments provide access to employment, they are significant only at…

The Inadequacy of Existing Far Provisions to Ensure Contractor Environmental Compliance

National Research Council Canada - National Science Library

MacDonald, Edward

1997-01-01

This thesis focuses on situations where the obligation is on the contractor, and examines the existing FAR provisions and clauses to explore whether they are adequate to ensure government contractor...

Practical strategies for increasing efficiency and effectiveness in critical care education.

Science.gov (United States)

Joyce, Maurice F; Berg, Sheri; Bittner, Edward A

2017-02-04

Technological advances and evolving demands in medical care have led to challenges in ensuring adequate training for providers of critical care. Reliance on the traditional experience-based training model alone is insufficient for ensuring quality and safety in patient care. This article provides a brief overview of the existing educational practice within the critical care environment. Challenges to education within common daily activities of critical care practice are reviewed. Some practical evidence-based educational approaches are then described which can be incorporated into the daily practice of critical care without disrupting workflow or compromising the quality of patient care. It is hoped that such approaches for improving the efficiency and efficacy of critical care education will be integrated into training programs.

Calcitonin and calcitonin receptor-like receptors: common themes with family B GPCRs?

Science.gov (United States)

Barwell, James; Gingell, Joseph J; Watkins, Harriet A; Archbold, Julia K; Poyner, David R; Hay, Debbie L

2012-05-01

The calcitonin receptor (CTR) and calcitonin receptor-like receptor (CLR) are two of the 15 human family B (or Secretin-like) GPCRs. CTR and CLR are of considerable biological interest as their pharmacology is moulded by interactions with receptor activity-modifying proteins. They also have therapeutic relevance for many conditions, such as osteoporosis, diabetes, obesity, lymphatic insufficiency, migraine and cardiovascular disease. In light of recent advances in understanding ligand docking and receptor activation in both the family as a whole and in CLR and CTR specifically, this review reflects how applicable general family B GPCR themes are to these two idiosyncratic receptors. We review the main functional domains of the receptors; the N-terminal extracellular domain, the juxtamembrane domain and ligand interface, the transmembrane domain and the intracellular C-terminal domain. Structural and functional findings from the CLR and CTR along with other family B GPCRs are critically appraised to gain insight into how these domains may function. The ability for CTR and CLR to interact with receptor activity-modifying proteins adds another level of sophistication to these receptor systems but means careful consideration is needed when trying to apply generic GPCR principles. This review encapsulates current thinking in the realm of family B GPCR research by highlighting both conflicting and recurring themes and how such findings relate to two unusual but important receptors, CTR and CLR. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Design and Discovery of Functionally Selective Serotonin 2C (5-HT2C) Receptor Agonists.

Science.gov (United States)

Cheng, Jianjun; McCorvy, John D; Giguere, Patrick M; Zhu, Hu; Kenakin, Terry; Roth, Bryan L; Kozikowski, Alan P

2016-11-10

On the basis of the structural similarity of our previous 5-HT 2C agonists with the melatonin receptor agonist tasimelteon and the putative biological cross-talk between serotonergic and melatonergic systems, a series of new (2,3-dihydro)benzofuran-based compounds were designed and synthesized. The compounds were evaluated for their selectivity toward 5-HT 2A , 5-HT 2B , and 5-HT 2C receptors in the calcium flux assay with the ultimate goal to generate selective 5-HT 2C agonists. Selected compounds were studied for their functional selectivity by comparing their transduction efficiency at the G protein signaling pathway versus β-arrestin recruitment. The most functionally selective compound (+)-7e produced weak β-arrestin recruitment and also demonstrated less receptor desensitization compared to serotonin in both calcium flux and phosphoinositide (PI) hydrolysis assays. We report for the first time that selective 5-HT 2C agonists possessing weak β-arrestin recruitment can produce distinct receptor desensitization properties.

Identification and functional analysis of pheromone and receptor genes in the B3 mating locus of Pleurotus eryngii.

Science.gov (United States)

Kim, Kyung-Hee; Kang, Young Min; Im, Chak Han; Ali, Asjad; Kim, Sun Young; Je, Hee-Jeong; Kim, Min-Keun; Rho, Hyun Su; Lee, Hyun Sook; Kong, Won-Sik; Ryu, Jae-San

2014-01-01

Pleurotus eryngii has recently become a major cultivated mushroom; it uses tetrapolar heterothallism as a part of its reproductive process. Sexual development progresses only when the A and B mating types are compatible. Such mating incompatibility occasionally limits the efficiency of breeding programs in which crossing within loci-shared strains or backcrossing strategies are employed. Therefore, understanding the mating system in edible mushroom fungi will help provide a short cut in the development of new strains. We isolated and identified pheromone and receptor genes in the B3 locus of P. eryngii and performed a functional analysis of the genes in the mating process by transformation. A genomic DNA library was constructed to map the entire mating-type locus. The B3 locus was found to contain four pheromone precursor genes and four receptor genes. Remarkably, receptor PESTE3.3.1 has just 34 amino acid residues in its C-terminal cytoplasmic region; therefore, it seems likely to be a receptor-like gene. Real-time quantitative RT-PCR (real-time qRT-PCR) revealed that most pheromone and receptor genes showed significantly higher expression in monokaryotic cells than dikaryotic cells. The pheromone genes PEphb3.1 and PEphb3.3 and the receptor gene PESTE3.3.1 were transformed into P5 (A3B4). The transformants were mated with a tester strain (A4B4), and the progeny showed clamp connections and a normal fruiting body, which indicates the proposed role of these genes in mating and fruiting processes. This result also confirms that PESTE3.3.1 is a receptor gene. In this study, we identified pheromone and receptor genes in the B3 locus of P. eryngii and found that some of those genes appear to play a role in the mating and fruiting processes. These results might help elucidate the mechanism of fruiting differentiation and improve breeding efficiency.

THE ROLE OF MORTGAGE CREDIT IN ENSURING ECONOMIC GROWTH

Directory of Open Access Journals (Sweden)

Z. L. Garipova

2014-04-01

Full Text Available The decision of the important social task - ensuring the availability of housing for the mass of the population of the country, on the one hand, allowed to launch investment, savings, financial and credit mechanisms for ensuring economic growth of the Russian economy on the other. Despite the high degree of sophistication in the scientific literature of the organization of mortgage lending system, a study of its impact on economic growth factors in the scientific literature clearly insufficient. The original article was the theory of economic growth, which allowed on the basis of research of interaction of demand for residential property, it deals with the housing mortgage credit to justify a conclusion about its importance not only for solution of social tasks, availability of housing, but also a significant impact on the demand and supply on the residential property market. Based on the analysis of statistical data for the period from 2006 to 2012, and their correlation analysis carried out research of factors of development of housing markets and mortgage lending, namely incomes, housing prices, interest rates on loans, «channel lending conditions, the terms of banking mortgage.Purchase on Elibrary.ru > Buy now

Investment-innovation mechanism of ensuring competitiveness of industrial enterprises

Directory of Open Access Journals (Sweden)

Kozyk Vasyl V.

2014-01-01

Full Text Available The article considers the process of formation of the investment-innovation mechanism of ensuring competitiveness of industrial enterprises. It identifies the essence, composition, goals and means of functioning of this mechanism. It establishes sequence of the process of functioning of the investment-innovation mechanism of ensuring competitiveness of economic subjects. It marks out such particular types of this mechanism: mechanism of renovation of fixed assets of an enterprise, mechanism of formation of channels and network of sales of enterprise products, mechanism of expansion of production capacity of the enterprise on manufacture of traditional types of products, mechanism of introduction of new progressive production processes, mechanism of development and production of innovation products, and mechanism of reduction of the level of risk of investment activity of the enterprise. The article conducts modelling of the process of development and realisation of investment solutions on introduction of progressive technologies of manufacture of products at the enterprise. It offers a method of selection of the most competitive variant of technology of manufacture of products depending on the level of quality and also specific current capital outlays for their manufacture.

Molecular modeling of ligand-receptor interactions in the OR5 olfactory receptor.

Science.gov (United States)

Singer, M S; Shepherd, G M

1994-06-02

Olfactory receptors belong to the superfamily of seven transmembrane domain, G protein-coupled receptors. In order to begin analysis of mechanisms of receptor activation, a computer model of the OR5 olfactory receptor has been constructed and compared with other members of this superfamily. We have tested docking of the odor molecule lyral, which is known to activate the OR5 receptor. The results point to specific ligand-binding residues on helices III through VII that form a binding pocket in the receptor. Some of these residues occupy sequence positions identical to ligand-binding residues conserved among other superfamily members. The results provide new insights into possible molecular mechanisms of odor recognition and suggest hypotheses to guide future experimental studies using site-directed mutagenesis.

Ligand-independent Thrombopoietin Mutant Receptor Requires Cell Surface Localization for Endogenous Activity*

Science.gov (United States)

Marty, Caroline; Chaligné, Ronan; Lacout, Catherine; Constantinescu, Stefan N.; Vainchenker, William; Villeval, Jean-Luc

2009-01-01

The activating W515L mutation in the thrombopoietin receptor (MPL) has been identified in primary myelofibrosis and essential thrombocythemia. MPL belongs to a subset of the cytokine receptor superfamily that requires the JAK2 kinase for signaling. We examined whether the ligand-independent MPLW515L mutant could signal intracellularly. Addition of the endoplasmic reticulum (ER) retention KDEL sequence to the receptor C terminus efficiently locked MPLW515L within its natural ER/Golgi maturation pathway. In contrast to cells expressing the parental MPLW515L, MPLW515L-KDEL-expressing FDC-P1 cells were unable to grow autonomously and to produce tumors in nude mice. When observed, tumor nodules resulted from in vivo selection of cells leaking the receptor at their surface. JAK2 co-immunoprecipitated with MPLW515L-KDEL but was not phosphorylated. We generated disulfide-bonded MPLW515L homodimers by the S402C substitution, both in the normal and KDEL context. Unlike MPLW515L-KDEL, MPLW515L-S402C-KDEL signaled constitutively and exhibited cell surface localization. These data establish that MPLW515L with appended JAK2 matures through the ER/Golgi system in an inactive conformation and suggest that the MPLW515L/JAK2 complex requires membrane localization for JAK2 phosphorylation, resulting in autonomous receptor signaling. PMID:19261614

Calculation of the efficiency of accounting outsourcing

Directory of Open Access Journals (Sweden)

H.I. Liakhovych

2018-04-01

Full Text Available To ensure the best performance, enterprises pass on individual business processes for outsourcing. However, the implementation of this step requires an assessment of the effectiveness of such actions. The purpose of the article is to analyze the approaches to assessing the effectiveness of accounting outsourcing and to develop proposals for its methodology, taking into account the main goal of reducing transaction costs. The article defines the composition of the elements of the cost of maintaining accounting in the enterprise. It is proved that the efficiency of accounting outsourcing should be considered in two aspects: 1 it is related to economic efficiency (saving of internal resources of the enterprise due to the transfer of business processes for accounting on outsourcing; 2 is related to the efficiency of the outsourcer's work and the uninterrupted functioning of the enterprise that has taken advantage of outsourcing services. In order to assess the efficiency of the company's services, the outsourcer proposes to use a methodology that takes into account the indicators: the timeliness of the execution of works and the provision of services in accordance with the terms of the contract on outsourcing; completeness of performance of works and provision of services in accordance with the terms of the contract on outsourcing.

Ensuring rigour and trustworthiness of qualitative research in clinical pharmacy.

Science.gov (United States)

Hadi, Muhammad Abdul; José Closs, S

2016-06-01

The use of qualitative research methodology is well established for data generation within healthcare research generally and clinical pharmacy research specifically. In the past, qualitative research methodology has been criticized for lacking rigour, transparency, justification of data collection and analysis methods being used, and hence the integrity of findings. Demonstrating rigour in qualitative studies is essential so that the research findings have the "integrity" to make an impact on practice, policy or both. Unlike other healthcare disciplines, the issue of "quality" of qualitative research has not been discussed much in the clinical pharmacy discipline. The aim of this paper is to highlight the importance of rigour in qualitative research, present different philosophical standpoints on the issue of quality in qualitative research and to discuss briefly strategies to ensure rigour in qualitative research. Finally, a mini review of recent research is presented to illustrate the strategies reported by clinical pharmacy researchers to ensure rigour in their qualitative research studies.

75 FR 81558 - Promoting More Efficient Use of Spectrum Through Dynamic Spectrum Use Technologies

Science.gov (United States)

2010-12-28

... request materials in accessible formats for people with disabilities (braille, large print, electronic... contractor, Best Copy and Printing, Inc., 445 12th Street, SW., Room, CY-B402, Washington, DC 20554. The full... services. Ensuring that the Commission can take advantage of these improved efficiencies will be critical...

Energy efficiency and performance indicators of European electricity market

Directory of Open Access Journals (Sweden)

Constantin DUGULEANĂ

2015-06-01

Full Text Available The electric power system plays a vital role in the development of every country, ensuring the “fuel” which feeds its economic motor. The efficient functioning of this motor is essential for economy. The efficiency and the performances of electric power systems are reflected on the living level of population, through the money spent and the satisfaction level of their needs. The continuity of power distribution process, the good communication between the suppliers and consumers, the promptitude of interventions, the environment protection - all these are aspects characterizing the performance level of power distribution systems. The paper analyzes the evolution of quality indicators of power distribution systems both for countries’ level and for population on European market of electricity.

Between military efficiency and democratic legitimacy. Mapping parliamentary war powers in contemporary democracies, 1989-2004

NARCIS (Netherlands)

Wagner, W.M.; Peters, D.

2011-01-01

Parliamentary approval can be of crucial importance to ensure the democratic legitimacy of military operations as it can establish public consent to the executive's use of force. But involving parliament in decisions to deploy military forces may have negative repercussions on the efficiency of

Toward Improved Rotor-Only Axial Fans—Part II: Design Optimization for Maximum Efficiency

DEFF Research Database (Denmark)

Sørensen, Dan Nørtoft; Thompson, M. C.; Sørensen, Jens Nørkær

2000-01-01

Numerical design optimization of the aerodynamic performance of axial fans is carried out, maximizing the efficiency in a designinterval of flow rates. Tip radius, number of blades, and angular velocity of the rotor are fixed, whereas the hub radius andspanwise distributions of chord length......, stagger angle, and camber angle are varied to find the optimum rotor geometry.Constraints ensure a pressure rise above a specified target and an angle of attack on the blades below stall. The optimizationscheme is used to investigate the dependence of maximum efficiency on the width of the design interval...

Application of modern analytical techniques to ensure seafood safety and authenticity

National Research Council Canada - National Science Library

Martinez, Iciar; James, David; Loréal, Henri

2005-01-01

.... The second part deals with methods to ensure seafood authenticity. One section of this report is dedicated to current legislation related to traceability and labelling in the United States of America and Europe...

Elementary Mathematics Specialists: Ensuring the Intersection of Research and Practice

Science.gov (United States)

McGatha, Maggie B.

2017-01-01

This paper provides a historical overview of the role and impact of elementary mathematics specialists as well as current implications and opportunities for the field. Furthermore, suggestions are offered for the mathematics education field for ensuring the intersection of practice and research. [For complete proceedings, see ED581294.

Modulating Estrogen Receptor-related Receptor-α Activity Inhibits Cell Proliferation*

OpenAIRE

Bianco, Stéphanie; Lanvin, Olivia; Tribollet, Violaine; Macari, Claire; North, Sophie; Vanacker, Jean-Marc

2009-01-01

High expression of the estrogen receptor-related receptor (ERR)-α in human tumors is correlated to a poor prognosis, suggesting an involvement of the receptor in cell proliferation. In this study, we show that a synthetic compound (XCT790) that modulates the activity of ERRα reduces the proliferation of various cell lines and blocks the G1/S transition of the cell cycle in an ERR...

Receptor binding properties and antinociceptive effects of chimeric peptides consisting of a micro-opioid receptor agonist and an ORL1 receptor antagonist.

Science.gov (United States)

Kawano, Susumu; Ito, Risa; Nishiyama, Miharu; Kubo, Mai; Matsushima, Tomoko; Minamisawa, Motoko; Ambo, Akihiro; Sasaki, Yusuke

2007-07-01

Receptor binding properties and antinociceptive activities of chimeric peptides linked by spacers were investigated. The peptides consisted of the micro-opioid receptor ligand dermorphin (Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH(2)) or its analog YRFB (Tyr-D-Arg-Phe-betaAla-NH(2)) linked to the ORL1 receptor ligand Ac-Arg-Tyr-Tyr-Arg-Ile-Lys-NH(2) (Ac-RYYRIK-NH(2)). All chimeric peptides were found to possess high receptor binding affinities for both micro-opioid and ORL1 receptors in mouse brain membranes although their binding affinities for both receptors in spinal membranes were significantly lower. Among them, chimeric peptide 2, which consists of dermorphin and Ac-RYYRIK-NH(2) connected by a long spacer, had the highest binding affinity towards both receptors. In the tail-flick test following intrathecal (i.t.) administration to mice, all chimeric peptides showed potent and dose-dependent antinociceptive activities with an ED(50) of 1.34-4.51 (pmol/mouse), nearly comparable to dermorphin alone (ED(50); 1.08 pmol/mouse). In contrast to their micro-opioid receptor binding profiles, intracerebroventricular (i.c.v.) administration of the chimeric peptides resulted in much less potent antinociceptive activity (ED(50) 5.55-100peptides, and the regulation of mu-opioid receptor-mediated antinociception in brain. The present chimeric peptides may be useful as pharmacological tools for studies on micro-opioid receptor/ORL1 receptor heterodimers.

Glutamate receptor agonists

DEFF Research Database (Denmark)

Vogensen, Stine Byskov; Greenwood, Jeremy R; Bunch, Lennart

2011-01-01

The neurotransmitter (S)-glutamate [(S)-Glu] is responsible for most of the excitatory neurotransmission in the central nervous system. The effect of (S)-Glu is mediated by both ionotropic and metabotropic receptors. Glutamate receptor agonists are generally a-amino acids with one or more...... stereogenic centers due to strict requirements in the agonist binding pocket of the activated state of the receptor. By contrast, there are many examples of achiral competitive antagonists. The present review addresses how stereochemistry affects the activity of glutamate receptor ligands. The review focuses...... mainly on agonists and discusses stereochemical and conformational considerations as well as biostructural knowledge of the agonist binding pockets, which is useful in the design of glutamate receptor agonists. Examples are chosen to demonstrate how stereochemistry not only determines how the agonist...

Exploring the existence of Kuznets curve in countries' environmental efficiency using DEA window analysis

Energy Technology Data Exchange (ETDEWEB)

Halkos, George Emm.; Tzeremes, Nickolaos G. [Department of Economics, University of Thessaly, Korai 43, 38333, Volos (Greece)

2009-05-15

This paper, using data envelopment (DEA) window analysis and generalized method of moments (GMM) estimators, examines the existence of a Kuznets type relationship between countries' environmental efficiency and national income. Specifically, it measures the environmental efficiency of 17 OECD countries by constructing environmental efficiency ratios for the time period 1980-2002. The analysis with the application of dynamic panel data reveals that there isn't a Kuznets type relationship between environmental efficiency and income. Allowing for dynamic effects we find that the adjustment to the target ratio is instantaneous. We also find that increased economic activity does not always ensure environmental protection and thus the path of growth is important in addition to the growth itself. (author)

A kinetic study of bitter taste receptor sensing using immobilized porcine taste bud tissues.

Science.gov (United States)

Wei, Lihui; Qiao, Lixin; Pang, Guangchang; Xie, Junbo

2017-06-15

At present, developing an efficient assay method for truly reflecting the real feelings of gustatory tissues is of great importance. In this study, a novel biosensor was fabricated to investigate the kinetic characteristics of the receptors in taste bud tissues sensing bitter substances for the first time. Porcine taste bud tissues were used as the sensing elements, and the sandwich-type sensing membrane was fixed onto a glassy carbon electrode for assembling the biosensor. With the developed sensor, the response currents induced by sucrose octaacetate, denatonium benzoate, and quercetin stimulating corresponding receptors were determined. The results demonstrated that the interaction between the analyst with their receptors were fitting to hyperbola (R 2 =0.9776, 0.9980 and 0.9601), and the activation constants were 8.748×10 -15 mol/L, 1.429×10 -12 mol/L, 6.613×10 -14 mol/L, respectively. The average number of receptors per cell was calculated as 1.75, 28.58, and 13.23, while the signal amplification factors were 1.08×10 4 , 2.89×10 3 and 9.76×10 4 . These suggest that the sensor can be used to quantitatively describe the interaction characteristics of cells or tissue receptors with their ligands, the role of cellular signaling cascade, the number of receptors, and the signal transmission pathways. Copyright © 2017 Elsevier B.V. All rights reserved.

Cocaine Inhibits Dopamine D2 Receptor Signaling via Sigma-1-D2 Receptor Heteromers

Science.gov (United States)

Navarro, Gemma; Moreno, Estefania; Bonaventura, Jordi; Brugarolas, Marc; Farré, Daniel; Aguinaga, David; Mallol, Josefa; Cortés, Antoni; Casadó, Vicent; Lluís, Carmen; Ferre, Sergi

2013-01-01

Under normal conditions the brain maintains a delicate balance between inputs of reward seeking controlled by neurons containing the D1-like family of dopamine receptors and inputs of aversion coming from neurons containing the D2-like family of dopamine receptors. Cocaine is able to subvert these balanced inputs by altering the cell signaling of these two pathways such that D1 reward seeking pathway dominates. Here, we provide an explanation at the cellular and biochemical level how cocaine may achieve this. Exploring the effect of cocaine on dopamine D2 receptors function, we present evidence of σ1 receptor molecular and functional interaction with dopamine D2 receptors. Using biophysical, biochemical, and cell biology approaches, we discovered that D2 receptors (the long isoform of the D2 receptor) can complex with σ1 receptors, a result that is specific to D2 receptors, as D3 and D4 receptors did not form heteromers. We demonstrate that the σ1-D2 receptor heteromers consist of higher order oligomers, are found in mouse striatum and that cocaine, by binding to σ1 -D2 receptor heteromers, inhibits downstream signaling in both cultured cells and in mouse striatum. In contrast, in striatum from σ1 knockout animals these complexes are not found and this inhibition is not seen. Taken together, these data illuminate the mechanism by which the initial exposure to cocaine can inhibit signaling via D2 receptor containing neurons, destabilizing the delicate signaling balance influencing drug seeking that emanates from the D1 and D2 receptor containing neurons in the brain. PMID:23637801

Impaired thromboxane receptor dimerization reduces signaling efficiency: A potential mechanism for reduced platelet function in vivo.

Science.gov (United States)

Capra, Valérie; Mauri, Mario; Guzzi, Francesca; Busnelli, Marta; Accomazzo, Maria Rosa; Gaussem, Pascale; Nisar, Shaista P; Mundell, Stuart J; Parenti, Marco; Rovati, G Enrico

2017-01-15

Thromboxane A 2 is a potent mediator of inflammation and platelet aggregation exerting its effects through the activation of a G protein-coupled receptor (GPCR), termed TP. Although the existence of dimers/oligomers in Class A GPCRs is widely accepted, their functional significance still remains controversial. Recently, we have shown that TPα and TPβ homo-/hetero-dimers interact through an interface of residues in transmembrane domain 1 (TM1) whose disruption impairs dimer formation. Here, biochemical and pharmacological characterization of this dimer deficient mutant (DDM) in living cells indicates a significant impairment in its response to agonists. Interestingly, two single loss-of-function TPα variants, namely W29C and N42S recently identified in two heterozygous patients affected by bleeding disorders, match some of the residues mutated in our DDM. These two naturally occurring variants display a reduced potency to TP agonists and are characterized by impaired dimer formation in transfected HEK-293T cells. These findings provide proofs that lack of homo-dimer formation is a crucial process for reduced TPα function in vivo, and might represent one molecular mechanism through which platelet TPα receptor dysfunction affects the patient(s) carrying these mutations. Copyright © 2016 Elsevier Inc. All rights reserved.

Receptor dose and patient dose in radiographic exposures: a 15 year review

International Nuclear Information System (INIS)

Peet, D.J.; Tyler, N.; Pryor, M.; Hollaway, P.; Strudley, C.; Leavesley, L.

2008-01-01

A patient dose programme has been established locally for the last 15 years across 109 hospitals and 250 X-ray rooms in line with the National Protocol, in conjunction with a programme to look at routine performance of these rooms. Routine performance checks initially looked primarily at film density and AEC performance but with the introduction of Computerised Radiography (CR) across UK hospitals and a revision of recommended procedures in the UK, the emphasis has shifted to assessing receptor dose under AEC control. Results show a wide variation in film density in the early years indicating sub optimal performance and dose. The spread was reduced over later years. The introduction of CR has led to a variety of approaches by the CR companies, X-ray companies and local sites. Receptor doses vary widely as a result. Large variations within hospitals were also observed. The doses over the last 15 years are reviewed and compared against diagnostic reference levels and with the performance of the imaging chain. Results show that patient dose programmes and optimisation strategies were having an impact, but the introduction of CR requires renewed efforts to ensure images and doses are optimised. (author)

On fair, effective and efficient REDD mechanism design

Directory of Open Access Journals (Sweden)

Gusti Mykola

2009-11-01

Full Text Available Abstract The issues surrounding 'Reduced Emissions from Deforestation and Forest Degradation' (REDD have become a major component of continuing negotiations under the United Nations Framework Convention on Climate Change (UNFCCC. This paper aims to address two key requirements of any potential REDD mechanism: first, the generation of measurable, reportable and verifiable (MRV REDD credits; and secondly, the sustainable and efficient provision of emission reductions under a robust financing regime. To ensure the supply of MRV credits, we advocate the establishment of an 'International Emission Reference Scenario Coordination Centre' (IERSCC. The IERSCC would act as a global clearing house for harmonized data to be used in implementing reference level methodologies. It would be tasked with the collection, reporting and subsequent processing of earth observation, deforestation- and degradation driver information in a globally consistent manner. The IERSCC would also assist, coordinate and supervise the computation of national reference scenarios according to rules negotiated under the UNFCCC. To overcome the threats of "market flooding" on the one hand and insufficient economic incentives for REDD on the other hand, we suggest an 'International Investment Reserve' (IIR as REDD financing framework. In order to distribute the resources of the IIR we propose adopting an auctioning mechanism. Auctioning not only reveals the true emission reduction costs, but might also allow for incentivizing the protection of biodiversity and socio-economic values. The introduced concepts will be vital to ensure robustness, environmental integrity and economic efficiency of the future REDD mechanism.

Function of the cytoplasmic tail of human calcitonin receptor-like receptor in complex with receptor activity-modifying protein 2

Energy Technology Data Exchange (ETDEWEB)

Kuwasako, Kenji, E-mail: kuwasako@fc.miyazaki-u.ac.jp [Frontier Science Research Center, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan); Kitamura, Kazuo; Nagata, Sayaka; Hikosaka, Tomomi [Division of Circulation and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan); Kato, Johji [Frontier Science Research Center, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan)

2010-02-12

Receptor activity-modifying protein 2 (RAMP2) enables calcitonin receptor-like receptor (CRLR) to form an adrenomedullin (AM)-specific receptor. Here we investigated the function of the cytoplasmic C-terminal tail (C-tail) of human (h)CRLR by co-transfecting its C-terminal mutants into HEK-293 cells stably expressing hRAMP2. Deleting the C-tail from CRLR disrupted AM-evoked cAMP production or receptor internalization, but did not affect [{sup 125}I]AM binding. We found that CRLR residues 428-439 are required for AM-evoked cAMP production, though deleting this region had little effect on receptor internalization. Moreover, pretreatment with pertussis toxin (100 ng/mL) led to significant increases in AM-induced cAMP production via wild-type CRLR/RAMP2 complexes. This effect was canceled by deleting CRLR residues 454-457, suggesting Gi couples to this region. Flow cytometric analysis revealed that CRLR truncation mutants lacking residues in the Ser/Thr-rich region extending from Ser{sup 449} to Ser{sup 467} were unable to undergo AM-induced receptor internalization and, in contrast to the effect on wild-type CRLR, overexpression of GPCR kinases-2, -3 and -4 failed to promote internalization of CRLR mutants lacking residues 449-467. Thus, the hCRLR C-tail is crucial for AM-evoked cAMP production and internalization of the CRLR/RAMP2, while the receptor internalization is dependent on the aforementioned GPCR kinases, but not Gs coupling.

Prostaglandin Receptor Signaling in Disease

Directory of Open Access Journals (Sweden)

Toshiyuki Matsuoka

2007-01-01

Full Text Available Prostanoids, consisting of the prostaglandins (PGs and the thromboxanes (TXs, are a group of lipid mediators formed in response to various stimuli. They include PGD2, PGE2, PGF2α, PGI2, and TXA2. They are released outside of the cells immediately after synthesis, and exert their actions by binding to a G-protein coupled rhodopsin-type receptor on the surface of target cells. There are eight types of the prostanoid receptors conserved in mammals from mouse to human. They are the PGD receptor (DP, four subtypes of the PGE receptor (EP1, EP2, EP3, and EP4, the PGF receptor (FP, PGI receptor (IP, and TXA receptor (TP. Recently, mice deficient in each of these prostanoid receptors were generated and subjected to various experimental models of disease. These studies have revealed the roles of PG receptor signaling in various pathological conditions, and suggest that selective manipulation of the prostanoid receptors may be beneficial in treatment of the pathological conditions. Here we review these recent findings of roles of prostanoid receptor signaling and their therapeutic implications.

Systematic and efficient side chain optimization for molecular docking using a cheapest-path procedure.

Science.gov (United States)

Schumann, Marcel; Armen, Roger S

2013-05-30

Molecular docking of small-molecules is an important procedure for computer-aided drug design. Modeling receptor side chain flexibility is often important or even crucial, as it allows the receptor to adopt new conformations as induced by ligand binding. However, the accurate and efficient incorporation of receptor side chain flexibility has proven to be a challenge due to the huge computational complexity required to adequately address this problem. Here we describe a new docking approach with a very fast, graph-based optimization algorithm for assignment of the near-optimal set of residue rotamers. We extensively validate our approach using the 40 DUD target benchmarks commonly used to assess virtual screening performance and demonstrate a large improvement using the developed side chain optimization over rigid receptor docking (average ROC AUC of 0.693 vs. 0.623). Compared to numerous benchmarks, the overall performance is better than nearly all other commonly used procedures. Furthermore, we provide a detailed analysis of the level of receptor flexibility observed in docking results for different classes of residues and elucidate potential avenues for further improvement. Copyright © 2013 Wiley Periodicals, Inc.

Receptor Autoradiography Protocol for the Localized Visualization of Angiotensin II Receptors.

Science.gov (United States)

Linares, Andrea; Couling, Leena E; Carrera, Eduardo J; Speth, Robert C

2016-06-07

This protocol describes receptor binding patterns for Angiotensin II (Ang II) in the rat brain using a radioligand specific for Ang II receptors to perform receptor autoradiographic mapping. Tissue specimens are harvested and stored at -80 °C. A cryostat is used to coronally section the tissue (brain) and thaw-mount the sections onto charged slides. The slide-mounted tissue sections are incubated in (125)I-SI-Ang II to radiolabel Ang II receptors. Adjacent slides are separated into two sets: 'non-specific binding' (NSP) in the presence of a receptor saturating concentration of non-radiolabeled Ang II, or an AT1 Ang II receptor subtype (AT1R) selective Ang II receptor antagonist, and 'total binding' with no AT1R antagonist. A saturating concentration of AT2 Ang II receptor subtype (AT2R) antagonist (PD123319, 10 µM) is also present in the incubation buffer to limit (125)I-SI-Ang II binding to the AT1R subtype. During a 30 min pre-incubation at ~22 °C, NSP slides are exposed to 10 µM PD123319 and losartan, while 'total binding' slides are exposed to 10 µM PD123319. Slides are then incubated with (125)I-SI-Ang II in the presence of PD123319 for 'total binding', and PD123319 and losartan for NSP in assay buffer, followed by several 'washes' in buffer, and water to remove salt and non-specifically bound radioligand. The slides are dried using blow-dryers, then exposed to autoradiography film using a specialized film and cassette. The film is developed and the images are scanned into a computer for visual and quantitative densitometry using a proprietary imaging system and a spreadsheet. An additional set of slides are thionin-stained for histological comparisons. The advantage of using receptor autoradiography is the ability to visualize Ang II receptors in situ, within a section of a tissue specimen, and anatomically identify the region of the tissue by comparing it to an adjacent histological reference section.

Expression of GABAergic receptors in mouse taste receptor cells.

Directory of Open Access Journals (Sweden)

Margaret R Starostik

Full Text Available BACKGROUND: Multiple excitatory neurotransmitters have been identified in the mammalian taste transduction, with few studies focused on inhibitory neurotransmitters. Since the synthetic enzyme glutamate decarboxylase (GAD for gamma-aminobutyric acid (GABA is expressed in a subset of mouse taste cells, we hypothesized that other components of the GABA signaling pathway are likely expressed in this system. GABA signaling is initiated by the activation of either ionotropic receptors (GABA(A and GABA(C or metabotropic receptors (GABA(B while it is terminated by the re-uptake of GABA through transporters (GATs. METHODOLOGY/PRINCIPAL FINDINGS: Using reverse transcriptase-PCR (RT-PCR analysis, we investigated the expression of different GABA signaling molecules in the mouse taste system. Taste receptor cells (TRCs in the circumvallate papillae express multiple subunits of the GABA(A and GABA(B receptors as well as multiple GATs. Immunocytochemical analyses examined the distribution of the GABA machinery in the circumvallate papillae. Both GABA(A-and GABA(B- immunoreactivity were detected in the peripheral taste receptor cells. We also used transgenic mice that express green fluorescent protein (GFP in either the Type II taste cells, which can respond to bitter, sweet or umami taste stimuli, or in the Type III GAD67 expressing taste cells. Thus, we were able to identify that GABAergic receptors are expressed in some Type II and Type III taste cells. Mouse GAT4 labeling was concentrated in the cells surrounding the taste buds with a few positively labeled TRCs at the margins of the taste buds. CONCLUSIONS/SIGNIFICANCE: The presence of GABAergic receptors localized on Type II and Type III taste cells suggests that GABA is likely modulating evoked taste responses in the mouse taste bud.

Oligonucleotide aptamers against tyrosine kinase receptors: Prospect for anticancer applications.

Science.gov (United States)

Camorani, Simona; Crescenzi, Elvira; Fedele, Monica; Cerchia, Laura

2018-04-01

Transmembrane receptor tyrosine kinases (RTKs) play crucial roles in cancer cell proliferation, survival, migration and differentiation. Area of intense research is searching for effective anticancer therapies targeting these receptors and, to date, several monoclonal antibodies and small-molecule tyrosine kinase inhibitors have entered the clinic. However, some of these drugs show limited efficacy and give rise to acquired resistance. Emerging highly selective compounds for anticancer therapy are oligonucleotide aptamers that interact with their targets by recognizing a specific three-dimensional structure. Because of their nucleic acid nature, the rational design of advanced strategies to manipulate aptamers for both diagnostic and therapeutic applications is greatly simplified over antibodies. In this manuscript, we will provide a comprehensive overview of oligonucleotide aptamers as next generation strategies to efficiently target RTKs in human cancers. Copyright © 2018 Elsevier B.V. All rights reserved.

Elite suppressor-derived HIV-1 envelope glycoproteins exhibit reduced entry efficiency and kinetics.

Directory of Open Access Journals (Sweden)

Kara G Lassen

2009-04-01

Full Text Available Elite suppressors (ES are a rare subset of HIV-1-infected individuals who are able to maintain HIV-1 viral loads below the limit of detection by ultra-sensitive clinical assays in the absence of antiretroviral therapy. Mechanism(s responsible for this elite control are poorly understood but likely involve both host and viral factors. This study assesses ES plasma-derived envelope glycoprotein (env fitness as a function of entry efficiency as a possible contributor to viral suppression. Fitness of virus entry was first evaluated using a novel inducible cell line with controlled surface expression levels of CD4 (receptor and CCR5 (co-receptor. In the context of physiologic CCR5 and CD4 surface densities, ES envs exhibited significantly decreased entry efficiency relative to chronically infected viremic progressors. ES envs also demonstrated slow entry kinetics indicating the presence of virus with reduced entry fitness. Overall, ES env clones were less efficient at mediating entry than chronic progressor envs. Interestingly, acute infection envs exhibited an intermediate phenotypic pattern not distinctly different from ES or chronic progressor envs. These results imply that lower env fitness may be established early and may directly contribute to viral suppression in ES individuals.

AMPA receptor ligands

DEFF Research Database (Denmark)

Strømgaard, Kristian; Mellor, Ian

2004-01-01

Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player in the f......Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player...... in the formation of memory. Hence, ligands affecting AMPARs are highly important for the study of the structure and function of this receptor, and in this regard polyamine-based ligands, particularly polyamine toxins, are unique as they selectively block Ca2+ -permeable AMPARs. Indeed, endogenous intracellular...

A2A-D2 receptor-receptor interaction modulates gliotransmitter release from striatal astrocyte processes.

Science.gov (United States)

Cervetto, Chiara; Venturini, Arianna; Passalacqua, Mario; Guidolin, Diego; Genedani, Susanna; Fuxe, Kjell; Borroto-Esquela, Dasiel O; Cortelli, Pietro; Woods, Amina; Maura, Guido; Marcoli, Manuela; Agnati, Luigi F

2017-01-01

Evidence for striatal A2A-D2 heterodimers has led to a new perspective on molecular mechanisms involved in schizophrenia and Parkinson's disease. Despite the increasing recognition of astrocytes' participation in neuropsychiatric disease vulnerability, involvement of striatal astrocytes in A2A and D2 receptor signal transmission has never been explored. Here, we investigated the presence of D2 and A2A receptors in isolated astrocyte processes prepared from adult rat striatum by confocal imaging; the effects of receptor activation were measured on the 4-aminopyridine-evoked release of glutamate from the processes. Confocal analysis showed that A2A and D2 receptors were co-expressed on the same astrocyte processes. Evidence for A2A-D2 receptor-receptor interactions was obtained by measuring the release of the gliotransmitter glutamate: D2 receptors inhibited the glutamate release, while activation of A2A receptors, per se ineffective, abolished the effect of D2 receptor activation. The synthetic D2 peptide VLRRRRKRVN corresponding to the receptor region involved in electrostatic interaction underlying A2A-D2 heteromerization abolished the ability of the A2A receptor to antagonize the D2 receptor-mediated effect. Together, the findings are consistent with heteromerization of native striatal astrocytic A2A-D2 receptors that via allosteric receptor-receptor interactions could play a role in the control of striatal glutamatergic transmission. These new findings suggest possible new pathogenic mechanisms and/or therapeutic approaches to neuropsychiatric disorders. © 2016 International Society for Neurochemistry.

Properties of GluR3 receptors tagged with GFP at the amino or carboxyl terminus.

Science.gov (United States)

Limon, Agenor; Reyes-Ruiz, Jorge Mauricio; Eusebi, Fabrizio; Miledi, Ricardo

2007-09-25

Anatomical visualization of neurotransmitter receptor localization is facilitated by tagging receptors, but this process can alter their functional properties. We have evaluated the distribution and properties of WT glutamate receptor 3 (GluR3) alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (WT GluR3) and two receptors in which GFP was tagged to the amino terminus (GFP-GluR3) or to the carboxyl terminus (GluR3-GFP). Although the fluorescence in Xenopus oocytes was stronger in the vegetal hemisphere because of localization of internal structures (probable sites of production, storage or recycling of receptors), the insertion of receptors into the plasma membrane was polarized to the animal hemisphere. The fluorescence intensity of oocytes injected with GluR3-GFP RNA was approximately double that of oocytes injected with GFP-GluR3 RNA. Accordingly, GluR3-GFP oocytes generated larger kainate-induced currents than GFP-GluR3 oocytes, with similar EC(50) values. Currents elicited by glutamate, or AMPA coapplied with cyclothiazide, were also larger in GluR3-GFP oocytes. The glutamate- to kainate-current amplitude ratios differed, with GluR3-GFP being activated more efficiently by glutamate than the WT or GFP-GluR3 receptors. This pattern correlates with the slower decay of glutamate-induced currents generated by GluR3-GFP receptors. These changes were not observed when GFP was tagged to the amino terminus, and these receptors behaved like the WT. The antagonistic effects of 6-nitro-7-sulfamoylbenzo[f]quinoxaline-2,3-dione (NBQX) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) were not altered in any of the tagged receptors. We conclude that GFP is a useful and convenient tag for visualizing these proteins. However, the effects of different sites of tag insertion on receptor characteristics must be taken into account in assessing the roles played by these receptor proteins.

Tool Efficiency Analysis model research in SEMI industry

Directory of Open Access Journals (Sweden)

Lei Ma

2018-01-01

Full Text Available One of the key goals in SEMI industry is to improve equipment through put and ensure equipment production efficiency maximization. This paper is based on SEMI standards in semiconductor equipment control, defines the transaction rules between different tool states，and presents a TEA system model which is to analysis tool performance automatically based on finite state machine. The system was applied to fab tools and verified its effectiveness successfully, and obtained the parameter values used to measure the equipment performance, also including the advices of improvement.

Global profiling of DNA replication timing and efficiency reveals that efficient replication/firing occurs late during S-phase in S. pombe.

Directory of Open Access Journals (Sweden)

Majid Eshaghi

Full Text Available BACKGROUND: During S. pombe S-phase, initiation of DNA replication occurs at multiple sites (origins that are enriched with AT-rich sequences, at various times. Current studies of genome-wide DNA replication profiles have focused on the DNA replication timing and origin location. However, the replication and/or firing efficiency of the individual origins on the genomic scale remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: Using the genome-wide ORF-specific DNA microarray analysis, we show that in S. pombe, individual origins fire with varying efficiencies and at different times during S-phase. The increase in DNA copy number plotted as a function of time is approximated to the near-sigmoidal model, when considering the replication start and end timings at individual loci in cells released from HU-arrest. Replication efficiencies differ from origin to origin, depending on the origin's firing efficiency. We have found that DNA replication is inefficient early in S-phase, due to inefficient firing at origins. Efficient replication occurs later, attributed to efficient but late-firing origins. Furthermore, profiles of replication timing in cds1Delta cells are abnormal, due to the failure in resuming replication at the collapsed forks. The majority of the inefficient origins, but not the efficient ones, are found to fire in cds1Delta cells after HU removal, owing to the firing at the remaining unused (inefficient origins during HU treatment. CONCLUSIONS/SIGNIFICANCE: Taken together, our results indicate that efficient DNA replication/firing occurs late in S-phase progression in cells after HU removal, due to efficient late-firing origins. Additionally, checkpoint kinase Cds1p is required for maintaining the efficient replication/firing late in S-phase. We further propose that efficient late-firing origins are essential for ensuring completion of DNA duplication by the end of S-phase.

Nuclear androgen receptors in human prostatic tissue. Extraction with heparin and estimation of the number of binding sites with different methods

International Nuclear Information System (INIS)

Foekens, J.A.; Bolt-de Vries, J.; Mulder, E.; Blankenstein, M.A.; Schroeder, F.H.; Molen, H.J. van der

1981-01-01

A procedure for the estimation of nuclear androgen receptors in benign prostatic hyperplastic tissue is described, which employs extraction of receptors from nuclei with buffers containing heparin. Extraction of a nuclear pellet with a heparin-containing (1 g/l) buffer appeared to have definite advantages over 0.4 mol/l KCl extraction. Heparin appeared to be twice as efficient in extracting androgen receptors. In addition aggregated receptor proteins, formed after storage at -80 0 C, were partly deaggregated by heparin. Specific isolation of the androgen receptor was performed using either agar gel electrophoresis, protamine sulphate precipitation or LH-20 gel filtration. A comparison was made between the amounts of estimated receptors with these different techniques. Protamine sulphate precipitation resulted in the highest estimates of receptor-bound 5α-[ 3 H]dihydrotestosterone ( 3 H-DHT). Treatment of the labelled nuclear extracts with a charcoal suspension prior to the receptor assay resulted in lower amounts of estimated androgen receptors. A method for routine evaluation of nuclear androgen receptors in prostatic tissue has been evaluated, which involves extraction of nuclear pellets with a heparin-containing (1 g/l) buffer, exchange labelling of the nuclear extracts for 20 h at 10 0 C and quantification of the receptors with protamine sulphate precipitation. (Auth.)

Prognostic Value of Estrogen Receptor alpha and Progesterone Receptor Conversion in Distant Breast Cancer Metastases

NARCIS (Netherlands)

Hoefnagel, Laurien D. C.; Moelans, Cathy B.; Meijer, S. L.; van Slooten, Henk-Jan; Wesseling, Pieter; Wesseling, Jelle; Westenend, Pieter J.; Bart, Joost; Seldenrijk, Cornelis A.; Nagtegaal, Iris D.; Oudejans, Joost; van der Valk, Paul; van Gils, Carla H.; van der Wall, Elsken; van Diest, Paul J.

2012-01-01

BACKGROUND: Changes in the receptor profile of primary breast cancers to their metastases (receptor conversion) have been described for the estrogen receptor alpha (ER alpha) and progesterone receptor (PR). The purpose of this study was to evaluate the impact of receptor conversion for ER alpha and

Effects of exhaust gas recirculation on the thermal efficiency and combustion characteristics for premixed combustion system

International Nuclear Information System (INIS)

Yu, Byeonghun; Kum, Sung-Min; Lee, Chang-Eon; Lee, Seungro

2013-01-01

In this research, a boiler in a premixed combustion system used to achieve exhaust gas recirculation was investigated as a way to achieve high thermal efficiencies and low pollutant emissions. The effects of various exhaust gas recirculation (EGR) ratios, equivalence ratios and boiler capacities on thermal efficiency, NO x and CO emissions and the flame behavior on the burner surface were examined both experimentally and numerically. The results of the experiments showed that when EGR was used, the NO x and CO concentrations decreased and the thermal efficiency increased. In the case of a 15% EGR ratio at an equivalence ratio of 0.90, NO x concentrations were found to be smaller than for the current operating condition of the boiler, and the thermal efficiency was approximately 4.7% higher. However, unlike NO x concentrations, although the EGR ratio was increased to 20% at an equivalence ratio of 0.90, the CO concentration was higher than in the current operating condition of the boiler. From the viewpoint of burner safety, the red glow on the burner surface was noticeably reduced when EGR was used. These results confirmed that the EGR method is advantageous from the standpoint of reducing emission concentrations and ensuring burner safety. -- Highlights: ► The premixed boiler system applied EGR was investigated to achieve high thermal efficiencies and low pollutant emissions. ► Thermal efficiency and emission characteristics were examined with EGR ratios, equivalence ratios and boiler capacities. ► EGR method is advantageous from the standpoint of reducing emission concentrations and ensuring burner safety.

Linking energy efficiency legislation and the agricultural sector in South Africa

Directory of Open Access Journals (Sweden)

Joseph N. Lekunze

2017-04-01

Full Text Available There are different ways of measuring energy efficiency. Although there is no generally agreed definition of the concept, it should, however, always be approached according to particular circumstances and contexts. As such, technological, operational, performance and equipment efficiencies should be taken into consideration. Generally, energy utilisation in most sectors of the South African economy is inefficient. This requires more energy needs to be generated in order to cater for losses. An increase in generation causes environmental problems at global, regional and local levels. A review of literature on energy efficiency was undertaken and a gap identified between legislation and efficiency in the agricultural sector. This article seeks to suggest ways of implementing an energy legislation in this sector in South Africa. Such implementation will address concerns in terms of harnessing, generating and utilising energy in different sectors in South Africa. Legislation is vital in reducing energy consumption in the agricultural sector. It also ensures efficient use of energy and the maintenance of current levels of production.

Economic-efficiency considerations in restructuring electric markets

Energy Technology Data Exchange (ETDEWEB)

Hill, L.J.

1996-12-01

In response to the Energy Policy Act of 1992 and the Federal Energy Regulatory Commission`s subsequent rulemaking on transmission access, many states are exploring options to restructure their electric industries. In their deliberations on restructuring, policymakers should consider (1) the reliability of the electric system; (2) income-distribution effects on ratepayers and utilities; (3) social consequences such as effects on energy conservation, renewable energy, and the environment; and (4) economic efficiency. We address economic-efficiency considerations in this study. Economic efficiency is important because it is one of the primary reasons that policymakers should consider restructuring in the first place: improving the electric-industry`s efficiency lowers costs and, hence, electric prices. In this study, we look at the sources of (in)efficiency in existing and proposed electric markets with the objective of guiding policymakers to design efficient electric markets. The advantages of a competitive market are well known: it leads to lower costs for the utility, lower prices for consumers, more product choices, better customer service, and often the need for less regulation by federal and state agencies. In the short run, firms who cannot produce at the market-clearing price are forced to leave the industry, ensuring that customers have the lowest price possible. In the long run, competition promotes innovation and lower costs. The physical and institutional characteristics of the U.S. electric industry, however, could be impediments to attaining efficiently run, competitive markets. Because of these characteristics, there are multiple sources of efficiencies and inefficiencies in existing electric markets, and there will be multiple sources in restructured ones. The objective of policymakers should not be to trade one set of inefficiencies in existing electric markets for another set in restructured markets.

Economic-efficiency considerations in restructuring electric markets

International Nuclear Information System (INIS)

Hill, L.J.

1996-12-01

In response to the Energy Policy Act of 1992 and the Federal Energy Regulatory Commission's subsequent rulemaking on transmission access, many states are exploring options to restructure their electric industries. In their deliberations on restructuring, policymakers should consider (1) the reliability of the electric system; (2) income-distribution effects on ratepayers and utilities; (3) social consequences such as effects on energy conservation, renewable energy, and the environment; and (4) economic efficiency. We address economic-efficiency considerations in this study. Economic efficiency is important because it is one of the primary reasons that policymakers should consider restructuring in the first place: improving the electric-industry's efficiency lowers costs and, hence, electric prices. In this study, we look at the sources of (in)efficiency in existing and proposed electric markets with the objective of guiding policymakers to design efficient electric markets. The advantages of a competitive market are well known: it leads to lower costs for the utility, lower prices for consumers, more product choices, better customer service, and often the need for less regulation by federal and state agencies. In the short run, firms who cannot produce at the market-clearing price are forced to leave the industry, ensuring that customers have the lowest price possible. In the long run, competition promotes innovation and lower costs. The physical and institutional characteristics of the U.S. electric industry, however, could be impediments to attaining efficiently run, competitive markets. Because of these characteristics, there are multiple sources of efficiencies and inefficiencies in existing electric markets, and there will be multiple sources in restructured ones. The objective of policymakers should not be to trade one set of inefficiencies in existing electric markets for another set in restructured markets

Microarray-Based Determination of Estrogen Receptor, Progesterone Receptor, and HER2 Receptor Status in Breast Cancer

NARCIS (Netherlands)

Roepman, Paul; Horlings, Hugo M.; Krijgsman, Oscar; Kok, Marleen; Bueno-de-Mesquita, Jolien M.; Bender, Richard; Linn, Sabine C.; Glas, Annuska M.; van de Vijver, Marc J.

2009-01-01

Purpose: The level of estrogen receptor (ER), progesterone receptor (PR), and HER2 aids in the determination of prognosis and treatment of breast cancer. Immunohistochemistry is currently the predominant method for assessment, but differences in methods and interpretation can substantially affect

Ensuring US National Aeronautics Test Capabilities

Science.gov (United States)

Marshall, Timothy J.

2010-01-01

U.S. leadership in aeronautics depends on ready access to technologically advanced, efficient, and affordable aeronautics test capabilities. These systems include major wind tunnels and propulsion test facilities and flight test capabilities. The federal government owns the majority of the major aeronautics test capabilities in the United States, primarily through the National Aeronautics and Space Administration (NASA) and the Department of Defense (DoD). However, changes in the Aerospace landscape, primarily the decrease in demand for testing over the last 20 years required an overarching strategy for management of these national assets. Therefore, NASA established the Aeronautics Test Program (ATP) as a two-pronged strategic initiative to: (1) retain and invest in NASA aeronautics test capabilities considered strategically important to the agency and the nation, and (2) establish a strong, high level partnership with the DoD. Test facility utilization is a critical factor for ATP because it relies on user occupancy fees to recover a substantial part of the operations costs for its facilities. Decreasing utilization is an indicator of excess capacity and in some cases low-risk redundancy (i.e., several facilities with basically the same capability and overall low utilization). However, low utilization does not necessarily translate to lack of strategic importance. Some facilities with relatively low utilization are nonetheless vitally important because of the unique nature of the capability and the foreseeable aeronautics testing needs. Unfortunately, since its inception, the customer base for ATP has continued to shrink. Utilization of ATP wind tunnels has declined by more than 50% from the FY 2006 levels. This significant decrease in customer usage is attributable to several factors, including the overall decline in new programs and projects in the aerospace sector; the impact of computational fluid dynamics (CFD) on the design, development, and research

The Essence and Phases of the Comprehensive System of Ensuring the Economic Security of Enterprise

Science.gov (United States)

Ianioglo, Alina; Polajeva, Tatjana

2017-01-01

In present conditions of instability of the environment, entrepreneurs assume the most of the business risks. In this regard, problems of ensuring the economic security become particularly important. The comprehensive system of ensuring the economic security of enterprise was worked out and the results are presented in the article. This system is…

CCAAT/Enhancer Binding Protein-β Is a Transcriptional Regulator of Peroxisome-Proliferator-Activated Receptor-γ Coactivator-1α in the Regenerating Liver

OpenAIRE

Wang, Haitao; Peiris, T. Harshani; Mowery, A.; Le Lay, John; Gao, Yan; Greenbaum, Linda E.

2008-01-01

The transcriptional coactivator peroxisome-proliferator-activated receptor-γ coactivator-1α (PGC-1α) is induced in the liver in response to fasting and coordinates the activation of targets necessary for increasing energy production for gluconeogenesis and ketogenesis. After partial hepatectomy, the liver must restore its mass while maintaining metabolic homeostasis to ensure survival. Here we report that PGC-1α is rapidly and dramatically induced after hepatectomy, with an amplitude of induc...

Process of Integrating Screening and Detailed Risk-based Modeling Analyses to Ensure Consistent and Scientifically Defensible Results

International Nuclear Information System (INIS)

Buck, John W.; McDonald, John P.; Taira, Randal Y.

2002-01-01

To support cleanup and closure of these tanks, modeling is performed to understand and predict potential impacts to human health and the environment. Pacific Northwest National Laboratory developed a screening tool for the United States Department of Energy, Office of River Protection that estimates the long-term human health risk, from a strategic planning perspective, posed by potential tank releases to the environment. This tool is being conditioned to more detailed model analyses to ensure consistency between studies and to provide scientific defensibility. Once the conditioning is complete, the system will be used to screen alternative cleanup and closure strategies. The integration of screening and detailed models provides consistent analyses, efficiencies in resources, and positive feedback between the various modeling groups. This approach of conditioning a screening methodology to more detailed analyses provides decision-makers with timely and defensible information and increases confidence in the results on the part of clients, regulators, and stakeholders

Fit fish. Energy-efficient gas management for aquaculture; Fitness fuer Fische. Energieeffizientes Gasemanagement fuer Aquakulturen

Energy Technology Data Exchange (ETDEWEB)

Anon.

2011-07-01

Fish farming is increasingly taking place on shore, using large inland tanks and pools. This conserves natural fish stocks and protects marine ecosystems. Linde engineers have developed a new, highly energy-efficient oxygenation system to ensure that salmon and other popular fish can thrive in the tank. (orig.)

How to ensure sustainable interoperability in heterogeneous distributed systems through architectural approach.

Science.gov (United States)

Pape-Haugaard, Louise; Frank, Lars

2011-01-01

A major obstacle in ensuring ubiquitous information is the utilization of heterogeneous systems in eHealth. The objective in this paper is to illustrate how an architecture for distributed eHealth databases can be designed without lacking the characteristic features of traditional sustainable databases. The approach is firstly to explain traditional architecture in central and homogeneous distributed database computing, followed by a possible approach to use an architectural framework to obtain sustainability across disparate systems i.e. heterogeneous databases, concluded with a discussion. It is seen that through a method of using relaxed ACID properties on a service-oriented architecture it is possible to achieve data consistency which is essential when ensuring sustainable interoperability.

A nano-graphite cold cathode for an energy-efficient cathodoluminescent light source

Directory of Open Access Journals (Sweden)

Alexander N. Obraztsov

2013-08-01

Full Text Available The development of new types of light sources is necessary in order to meet the growing demands of consumers and to ensure an efficient use of energy. The cathodoluminescence process is still under-exploited for light generation because of the lack of cathodes suitable for the energy-efficient production of electron beams and appropriate phosphor materials. In this paper we propose a nano-graphite film material as a highly efficient cold cathode, which is able to produce high intensity electron beams without energy consumption. The nano-graphite film material was produced by using chemical vapor deposition techniques. Prototypes of cathodoluminescent lamp devices with a construction optimized for the usage of nano-graphite cold cathodes were developed, manufactured and tested. The results indicate prospective advantages of this type of lamp and the possibility to provide advanced power efficiency as well as enhanced spectral and other characteristics.

Efficiency of Mechanisms for Ensuring Financial Stability in Developed Countries

Directory of Open Access Journals (Sweden)

Mizjuk Bohdan M.

2016-08-01

Full Text Available The aim of the article is to identify relationships between the monetary policy and long-term financial stability. The main method of the study is retrospective analysis of macroeconomic and financial performance of the United States and other developed countries. It has been shown that neither Neo-Keynesian nor monetarist approaches are able to provide long-term financial stability under simultaneous low levels of volatility of GDP and inflation. In addition, the policy of inflation targeting in developed countries is not able to eliminate the risk of significant macro-economic recessions. The article states that the cause of the recessions is a systemic risk growth due to concentration of financial resources in the banking sector and in the hands of owners of non-financial corporations. This concentration has two effects: 1 growth of moral hazard at crediting; 2 decrease in the effective demand on the part of households. Redistribution of financial resources among different macro-economic groups of agents does not happen in a short period of time and is a result of the long-term monetary policy. Since the modern economic statistics has certain methodological problems with calculation of the Gini coefficient, such indicator as a share of wages in GDP is proposed in the article for studying the dynamics of uneven distribution of financial resources in the United States. The conducted retrospective analysis of the US monetary policy showed that an important system indicator of uniformity of financial resources distribution among macroeconomic agents falls out of sight of regulators. Distribution of macroeconomic risks depends on distribution of financial resources in the system, which determines its financial stability. The article justifies the need for developing the monetary policy methods that would simultaneously minimize the volatility of the GDP, inflation and maintain a uniform distribution of financial resources at an acceptable level.

The Cellular Mechanisms that Ensure an Efficient Secretion in Streptomyces

Directory of Open Access Journals (Sweden)

Sonia Gullón

2018-04-01

Full Text Available Gram-positive soil bacteria included in the genus Streptomyces produce a large variety of secondary metabolites in addition to extracellular hydrolytic enzymes. From the industrial and commercial viewpoints, the S. lividans strain has generated greater interest as a host bacterium for the overproduction of homologous and heterologous hydrolytic enzymes as an industrial application, which has considerably increased scientific interest in the characterization of secretion routes in this bacterium. This review will focus on the secretion machinery in S. lividans.

Homeostatic proliferation fails to efficiently reactivate HIV-1 latently infected central memory CD4+ T cells.

Directory of Open Access Journals (Sweden)

Alberto Bosque

2011-10-01

Full Text Available Homeostatic proliferation ensures the longevity of central memory T-cells by inducing cell proliferation in the absence of cellular differentiation or activation. This process is governed mainly by IL-7. Central memory T-cells can also be stimulated via engagement of the T-cell receptor, leading to cell proliferation but also activation and differentiation. Using an in vitro model of HIV-1 latency, we have examined in detail the effects of homeostatic proliferation on latently infected central memory T cells. We have also used antigenic stimulation via anti-CD3/anti-CD28 antibodies and established a comparison with a homeostatic proliferation stimulus, to evaluate potential differences in how either treatment affects the dynamics of latent virus populations. First, we show that homeostatic proliferation, as induced by a combination of IL-2 plus IL-7, leads to partial reactivation of latent HIV-1 but is unable to reduce the size of the reservoir in vitro. Second, latently infected cells are able to homeostatically proliferate in the absence of viral reactivation or cell differentiation. These results indicate that IL-2 plus IL-7 may induce a detrimental effect by favoring the maintenance of the latent HIV-1 reservoir. On the other hand, antigenic stimulation efficiently reactivated latent HIV-1 in cultured central memory cells and led to depletion of the latently infected cells via virus-induced cell death.

[11C]-MeJDTic: a novel radioligand for κ-opioid receptor positron emission tomography imaging

International Nuclear Information System (INIS)

Poisnel, Geraldine; Oueslati, Farhana; Dhilly, Martine; Delamare, Jerome; Perrio, Cecile; Debruyne, Daniele; Barre, Louisa

2008-01-01

Introduction: Radiopharmaceuticals that can bind selectively the κ-opioid receptor may present opportunities for staging clinical brain disorders and evaluating the efficiency of new therapies related to stroke, neurodegenerative diseases or opiate addiction. The N-methylated derivative of JDTic (named MeJDTic), which has been recently described as a potent and selective antagonist of κ-opioid receptor in vitro, was labeled with carbon-11 and evaluated for in vivo imaging the κ-opioid receptor in mice. Methods: [ 11 C]-MeJDTic was prepared by methylation of JDTic with [ 11 C]-methyl triflate. The binding of [ 11 C]-MeJDTic to κ-opioid receptor was investigated ex vivo by biodistribution and competition studies using nonfasted male CD1 mice. Results: [ 11 C]-MeJDTic exhibited a high and rapid distribution in peripheral organs. The uptake was maximal in lung where the κ receptor is largely expressed. [ 11 C]-MeJDTic rapidly crossed the blood-brain barrier and accumulated in the brain regions of interest (hypothalamus). The parent ligand remained the major radioactive compound in brain during the experiment. Chase studies with U50,488 (a κ referring agonist), morphine (a μ agonist) and naltrindole (a δ antagonist) demonstrated that this uptake was the result of specific binding to the κ-opioid receptor. Conclusion: These findings suggested that [ 11 C]-MeJDTic appeared to be a promising selective 'lead' radioligand for κ-opioid receptor PET imaging

Energy policy for Europe. Ensuring secure and low-carbon energy in the EU's internal market. Interim report

International Nuclear Information System (INIS)

Egenhofer, C.; Hammes, J.J.; Pedersen, K.

2006-12-01

In early March 2006, the European Commission re-launched the discussion on an Energy Policy for Europe with the 2006 publication of its Green Paper 'Secure, Competitive and Sustainable Energy for Europe'. This manifests the EU's will to broaden its reflection on its future energy systems, taking into account increasing market liberalisation and globalisation, environmental pressures, technological challenges and the growing import dependency from politically unstable regions. Other major contributions to this debate include the climate change communication 'Winning the battle against climate change' (published in 2005), the Green Paper on Energy Efficiency (2005), the Energy Efficiency Action Plan (2006), the ongoing works of the High Level Group on Competitiveness, Energy and the Environment (2006) and the enquiry into the energy sector by DG Competition of the European Commission in 2006. The Spring European Council in March 2006 welcomed the Energy Policy Green Paper and committed itself adopting a prioritised Action Plan at its spring session in 2007, to be prepared by the European Commission and the Energy Council. Early next year, the European Commission will table both the EU Strategic Energy Review, accompanied by a number of sectoral policies and a Green Paper on future climate change policy for the period post-2012 when the Kyoto Protocol expires. Both the EU Strategic Energy Review and the post-2012 Green Paper will outline the European Union (EU) 'energy and climate change vision' and propose a roadmap towards achieving EU energy and climate change objectives, namely, how to ensure the competitiveness of European industries while at the same time combating climate change and ensuring security of energy supply. To contribute to this debate, the CEPS multi-stakeholder Task Force on 'energy policy for Europe' has presented this Interim Report, which attempts to develop the key elements for an EU energy policy framework. Although this report will focus

The Orphan Nuclear Receptor TR4 Is a Vitamin A-activated Nuclear Receptor

Energy Technology Data Exchange (ETDEWEB)

Zhou, X. Edward; Suino-Powell, Kelly M.; Xu, Yong; Chan, Cee-Wah; Tanabe, Osamu; Kruse, Schoen W.; Reynolds, Ross; Engel, James Douglas; Xu, H. Eric (Michigan-Med); (Van Andel)

2015-11-30

Testicular receptors 2 and 4 (TR2/4) constitute a subgroup of orphan nuclear receptors that play important roles in spermatogenesis, lipid and lipoprotein regulation, and the development of the central nervous system. Currently, little is known about the structural features and the ligand regulation of these receptors. Here we report the crystal structure of the ligand-free TR4 ligand binding domain, which reveals an autorepressed conformation. The ligand binding pocket of TR4 is filled by the C-terminal half of helix 10, and the cofactor binding site is occupied by the AF-2 helix, thus preventing ligand-independent activation of the receptor. However, TR4 exhibits constitutive transcriptional activity on multiple promoters, which can be further potentiated by nuclear receptor coactivators. Mutations designed to disrupt cofactor binding, dimerization, or ligand binding substantially reduce the transcriptional activity of this receptor. Importantly, both retinol and retinoic acid are able to promote TR4 to recruit coactivators and to activate a TR4-regulated reporter. These findings demonstrate that TR4 is a ligand-regulated nuclear receptor and suggest that retinoids might have a much wider regulatory role via activation of orphan receptors such as TR4.

Soman- or kainic acid-induced convulsions decrease muscarinic receptors but not benzodiazepine receptors

International Nuclear Information System (INIS)

Churchill, L.; Pazdernik, T.L.; Cross, R.S.; Nelson, S.R.; Samson, F.E.

1990-01-01

[3H]Quinuclidinyl benzilate (QNB) binding to muscarinic receptors decreased in the rat forebrain after convulsions induced by a single dose of either soman, a potent inhibitor of acetylcholinesterase, or kainic acid, an excitotoxin. A Rosenthal plot revealed that the receptors decreased in number rather than affinity. When the soman-induced convulsions were blocked, the decrease in muscarinic receptors at 3 days was less extensive than when convulsions occurred and at 10 days they approached control levels in most of the brain areas. The most prominent decrements in QNB binding were in the piriform cortex where the decline in QNB binding is probably related to the extensive convulsion-associated neuropathology. The decrements in QNB binding after convulsions suggest that the convulsive state leads to a down-regulation of muscarinic receptors in some brain areas. In contrast to the decrease in QNB binding after convulsions, [3H]flunitrazepam binding to benzodiazepine receptors did not change even in the piriform cortex where the loss in muscarinic receptors was most prominent. Thus, it appears that those neuronal processes that bear muscarinic receptors are more vulnerable to convulsion-induced change than those with benzodiazepine receptors

Barriers and opportunities for labels for highly energy-efficient houses

International Nuclear Information System (INIS)

Mlecnik, Erwin; Visscher, Henk; Van Hal, Anke

2010-01-01

Promoting energy efficiency in the building sector is essential if the agreements of the Kyoto Protocol are to be honoured. Different initiatives for energy labelling of highly energy-efficient residential buildings have emerged throughout Europe as an essential method to stimulate market demand, to control grants or to ensure the quality of demonstration projects with excellent energy performance. The paper identifies the barriers and opportunities for the further diffusion of labels for highly energy-efficient houses. A model based on the theory of the diffusion of innovation is developed to analyse perceived attributes of existing European labels. The paper investigates the innovation characteristics of existing labels in Europe, with a focus on advanced countries. The question of compatibility with the development of the European Energy Performance of Buildings Directive (EPBD) is examined in detail. We found that the diffusion of emerging and already existing voluntary European labels for highly energy-efficient houses is needed. Their complexity can be lowered and relative advantage, trialability, observability, and compatibility can be increased. EPBD calculation procedures should be able to receive highly energy-efficient houses. In the framework of the recast of the EPBD, official recognition of existing voluntary labels is recommended. (author)

Efficient T-cell surveillance of the CNS requires expression of the CXC chemokine receptor 3

DEFF Research Database (Denmark)

Christensen, Jeanette Erbo; Nansen, Anneline; Moos, Torben

2004-01-01

T-cells play an important role in controlling viral infections inside the CNS. To study the role of the chemokine receptor CXCR3 in the migration and positioning of virus-specific effector T-cells within the brain, CXCR3-deficient mice were infected intracerebrally with lymphocytic choriomeningitis......-cell-mediated immunopathology. Quantitative analysis of the cellular infiltrate in CSF of infected mice revealed modest, if any, decrease in the number of mononuclear cells recruited to the meninges in the absence of CXCR3. However, immunohistological analysis disclosed a striking impairment of CD8+ T-cells from CXCR3...

Semi-automating the manual literature search for systematic reviews increases efficiency.

Science.gov (United States)

Chapman, Andrea L; Morgan, Laura C; Gartlehner, Gerald

2010-03-01

To minimise retrieval bias, manual literature searches are a key part of the search process of any systematic review. Considering the need to have accurate information, valid results of the manual literature search are essential to ensure scientific standards; likewise efficient approaches that minimise the amount of personnel time required to conduct a manual literature search are of great interest. The objective of this project was to determine the validity and efficiency of a new manual search method that utilises the scopus database. We used the traditional manual search approach as the gold standard to determine the validity and efficiency of the proposed scopus method. Outcome measures included completeness of article detection and personnel time involved. Using both methods independently, we compared the results based on accuracy of the results, validity and time spent conducting the search, efficiency. Regarding accuracy, the scopus method identified the same studies as the traditional approach indicating its validity. In terms of efficiency, using scopus led to a time saving of 62.5% compared with the traditional approach (3 h versus 8 h). The scopus method can significantly improve the efficiency of manual searches and thus of systematic reviews.

In times of change: How distance managers can ensure employees’ wellbeing and organizational performance

DEFF Research Database (Denmark)

Poulsen, Signe; Ipsen, Christine

2017-01-01

. The analysis of distance managers’ practices showed that they used both activities and capabilities in order to ensure employee wellbeing and organizational performance. The activities included planning, newsletters, and surveys, and the capabilities were to listen, create and show trust, and give authority...... to the employees. Contrary to previous findings on motivating of knowledge workers, our findings show that motivation, surprisingly, is ensured when focusing on the basic needs such as working conditions and belongingness....

Cooperative ethylene receptor signaling

OpenAIRE

Liu, Qian; Wen, Chi-Kuang

2012-01-01

The gaseous plant hormone ethylene is perceived by a family of five ethylene receptor members in the dicotyledonous model plant Arabidopsis. Genetic and biochemical studies suggest that the ethylene response is suppressed by ethylene receptor complexes, but the biochemical nature of the receptor signal is unknown. Without appropriate biochemical measures to trace the ethylene receptor signal and quantify the signal strength, the biological significance of the modulation of ethylene responses ...

Correcting Detector Efficiency Effects in Event-by-Event Net-Proton Fluctuations

CERN Document Server

Peters, Michael

2016-01-01

Measurements of fluctuations of conserved quantities give valuable information on the susceptibilities of the nuclear matter produced in a heavy-ion collision, and could in principle be used to distinguish QGP from hadronic matter. However, measurements of the cumulants of conserved-quantity distributions are affected by the detector efficiency, which must be accounted for in order to ensure accuracy. Following the development of a toy model that simulates detector efficiency effects on net-proton number, various correction methods, including those developed by A. Bzdak and V. Koch, were implemented and tested in a wide range of conditions. We find that the first four cumulants of net-proton-number distribution can be accurately reproduced by the Koch-Bzdak corrections with reasonable input statistics. Various methods of correcting for $p_T$ dependence of detector efficiency are also explored.

Radiolabelled GLP-1 receptor antagonist binds to GLP-1 receptor-expressing human tissues

International Nuclear Information System (INIS)

Waser, Beatrice; Reubi, Jean Claude

2014-01-01

Radiolabelled glucagon-like peptide 1 (GLP-1) receptor agonists have recently been shown to successfully image benign insulinomas in patients. For the somatostatin receptor targeting of tumours, however, it was recently reported that antagonist tracers were superior to agonist tracers. The present study therefore evaluated various forms of the 125 iodinated-Bolton-Hunter (BH)-exendin(9-39) antagonist tracer for the in vitro visualization of GLP-1 receptor-expressing tissues in rats and humans and compared it with the agonist tracer 125 I-GLP-1(7-36)amide. Receptor autoradiography studies with 125 I-GLP-1(7-36)amide agonist or 125 I-BH-exendin(9-39) antagonist radioligands were performed in human and rat tissues. The antagonist 125 I-BH-exendin(9-39) labelled at lysine 19 identifies all human and rat GLP-1 target tissues and GLP-1 receptor-expressing tumours. Binding is of high affinity and is comparable in all tested tissues in its binding properties with the agonist tracer 125 I-GLP-1(7-36)amide. For comparison, 125 I-BH-exendin(9-39) with the BH labelled at lysine 4 did identify the GLP-1 receptor in rat tissues but not in human tissues. The GLP-1 receptor antagonist exendin(9-39) labelled with 125 I-BH at lysine 19 is an excellent GLP-1 radioligand that identifies human and rat GLP-1 receptors in normal and tumoural tissues. It may therefore be the molecular basis to develop suitable GLP-1 receptor antagonist radioligands for in vivo imaging of GLP-1 receptor-expressing tissues in patients. (orig.)

TECHNICAL MAINTENANCE EFFICIENCY OF THE AIRCRAFT MAINTENANCE-FREE ON-BOARD SYSTEM BETWEEN SCHEDULED MAINTENANCES

Directory of Open Access Journals (Sweden)

A. M. Bronnikov

2017-01-01

Full Text Available The avionics concept of the maintenance-free on-board equipment implies the absence of necessity to maintain onboard systems between scheduled maintenance, preserving the required operational and technical characteristics; it should be achieved by automatic diagnosis of the technical condition and the application of active means of ensuring a failsafe design, allowing to change the structure of the system to maintain its functions in case of failure. It is supposed that such equipment will reduce substantially and in the limit eliminate traditional maintenance of aircraft between scheduled maintenance, ensuring maximum readiness for use, along with improving safety. The paper proposes a methodology for evaluating the efficiency of maintenance-free between scheduled maintenance aircraft system with homogeneous redundancy. The excessive redundant elements allow the system to accumulate failures which are repaired during the routine maintenance. If the number of failures of any reserve is approaching a critical value, the recovery of the on-board system (elimination of all failures is carried out between scheduled maintenance by conducting rescue and recovery operations. It is believed that service work leads to the elimination of all failures and completely updates the on-board system. The process of system operational status changes is described with the discrete-continuous model in the flight time. The average losses in the sorties and the average cost of operation are used as integrated efficiency indicators of system operation. For example, the evaluation of the operation efficiency of formalized on-board system with homogeneous redundancy demonstrates the efficiency of the proposed methodology and the possibility of its use while analyzing the efficiency of the maintenance-free operation equipment between scheduled periods. As well as a comparative analysis of maintenance-free operation efficiency of the on-board system with excessive

A novel technique for detection efficiency determination of HPGe

International Nuclear Information System (INIS)

Tayyebi, Pouneh; Abbasi Davani, Fereydoun; Tabasi, Mohsen; Afarideh, Hossein

2017-01-01

In this work, we present an experimental method to determine the detection efficiency of HPGe when the reference source according to the geometry of interest is not accessible. We use known activity point sources (PS) of 152 Eu, 137 Cs, 241 Am and 133 Ba to find the detection efficiency for disc source (DS) geometry. It can be assumed that a DS consists of several PS's. Mapping the detector surface by means of 137 Cs PS shows that there is radial symmetry for detection efficiency vs. energy. Each radial distance on the detector surface contains some points, which can be considered as a PS. By selecting two points in two different radii and central point, the DS efficiency is obtained. To ensure that the method is correct, we measure the activity of a known activity DS considering DS efficiency obtained by PS's. The DS comprises 137 Cs, 133 Ba and 60 Co. The relative difference between the measured and the reported activity of DS in most energies is less than 5%. - Highlights: • Exact knowledge of the detector dimension is not necessary • There is no need to have standard source according to the sample • It is a simple method that can be done at any laboratories

Effect of neoadjuvant chemotherapy on low-density lipoprotein (LDL) receptor and LDL receptor-related protein 1 (LRP-1) receptor in locally advanced breast cancer

International Nuclear Information System (INIS)

Pires, L.A.; Hegg, R.; Freitas, F.R.; Tavares, E.R.; Almeida, C.P.; Baracat, E.C.; Maranhão, R.C.

2012-01-01

Low-density lipoprotein (LDL) receptors are overexpressed in most neoplastic cell lines and provide a mechanism for the internalization and concentration of drug-laden nanoemulsions that bind to these receptors. The aim of the present study was to determine whether the administration of standard chemotherapeutic schemes can alter the expression of LDL and LDL receptor-related protein 1 (LRP-1) receptors in breast carcinoma. Fragments of tumoral and normal breast tissue from 16 consecutive volunteer women with breast cancer in stage II or III were obtained from biopsies before the beginning of neoadjuvant chemotherapy and after chemotherapy, from fragments excised during mastectomy. Tissues were analyzed by immunohistochemistry for both receptors. Because complete response to treatment was achieved in 4 patients, only the tumors from 12 were analyzed. Before chemotherapy, there was overexpression of LDL receptor in the tumoral tissue compared to normal breast tissue in 8 of these patients. LRP-1 receptor overexpression was observed in tumors of 4 patients. After chemotherapy, expression of both receptors decreased in the tumors of 6 patients, increased in 4 and was unchanged in 2. Nonetheless, even when chemotherapy reduced receptors expression, the expression was still above normal. The fact that chemotherapy does not impair LDL receptors expression supports the use of drug carrier systems that target neoplastic cells by the LDL receptor endocytic pathway in patients on conventional chemotherapy

Systems and processes that ensure high quality care.

Science.gov (United States)

Bassett, Sally; Westmore, Kathryn

2012-10-01

This is the second in a series of articles examining the components of good corporate governance. It considers how the structures and processes for quality governance can affect an organisation's ability to be assured about the quality of care. Complex information systems and procedures can lead to poor quality care, but sound structures and processes alone are insufficient to ensure good governance, and behavioural factors play a significant part in making sure that staff are enabled to provide good quality care. The next article in this series looks at how the information reporting of an organisation can affect its governance.

CYLD Limits Lys63- and Met1-Linked Ubiquitin at Receptor Complexes to Regulate Innate Immune Signaling

Directory of Open Access Journals (Sweden)

Matous Hrdinka

2016-03-01

Full Text Available Innate immune signaling relies on the deposition of non-degradative polyubiquitin at receptor-signaling complexes, but how these ubiquitin modifications are regulated by deubiquitinases remains incompletely understood. Met1-linked ubiquitin (Met1-Ub is assembled by the linear ubiquitin assembly complex (LUBAC, and this is counteracted by the Met1-Ub-specific deubiquitinase OTULIN, which binds to the catalytic LUBAC subunit HOIP. In this study, we report that HOIP also interacts with the deubiquitinase CYLD but that CYLD does not regulate ubiquitination of LUBAC components. Instead, CYLD limits extension of Lys63-Ub and Met1-Ub conjugated to RIPK2 to restrict signaling and cytokine production. Accordingly, Met1-Ub and Lys63-Ub were individually required for productive NOD2 signaling. Our study thus suggests that LUBAC, through its associated deubiquitinases, coordinates the deposition of not only Met1-Ub but also Lys63-Ub to ensure an appropriate response to innate immune receptor activation.

The reHABITAT Guide: For Energy- and Resource-Efficient Retrofit Strategies; February 2003--February 2004

Energy Technology Data Exchange (ETDEWEB)

2004-07-01

The reHABITAT Guide for Energy- and Resource-Efficient Retrofit Strategies seeks to advance the goal of the U.S. Department of Energy's Existing Residential Buildings Program (ERBP): to develop approaches that will enable the housing retrofit industry to deliver energy-efficient housing improvements and to ensure that energy-efficient retrofit technologies incorporated into projects are viable over conventional approaches. This guide was developed for Habitat for Humanity International and is the result of lessons learned from demonstration retrofit projects undertaken by Habitat for Humanity affiliates in Newburgh, New York; Baltimore, Maryland; and Philadelphia, Pennsylvania; with building systems consulting and technical assistance provided by Steven Winter Associates, Inc. (SWA).

Oxytocin, vasopressin and estrogen receptor gene expression in relation to social recognition in female mice.

Science.gov (United States)

Clipperton-Allen, Amy E; Lee, Anna W; Reyes, Anny; Devidze, Nino; Phan, Anna; Pfaff, Donald W; Choleris, Elena

2012-02-28

Inter- and intra-species differences in social behavior and recognition-related hormones and receptors suggest that different distribution and/or expression patterns may relate to social recognition. We used qRT-PCR to investigate naturally occurring differences in expression of estrogen receptor-alpha (ERα), ER-beta (ERβ), progesterone receptor (PR), oxytocin (OT) and receptor, and vasopressin (AVP) and receptors in proestrous female mice. Following four 5 min exposures to the same two conspecifics, one was replaced with a novel mouse in the final trial (T5). Gene expression was examined in mice showing high (85-100%) and low (40-60%) social recognition scores (i.e., preferential novel mouse investigation in T5) in eight socially-relevant brain regions. Results supported OT and AVP involvement in social recognition, and suggest that in the medial preoptic area, increased OT and AVP mRNA, together with ERα and ERβ gene activation, relate to improved social recognition. Initial social investigation correlated with ERs, PR and OTR in the dorsolateral septum, suggesting that these receptors may modulate social interest without affecting social recognition. Finally, increased lateral amygdala gene activation in the LR mice may be associated with general learning impairments, while decreased lateral amygdala activity may indicate more efficient cognitive mechanisms in the HR mice. Copyright © 2011 Elsevier Inc. All rights reserved.

Evaluation of the factors that ensure long-term sustainability of family ...

African Journals Online (AJOL)

Results show that the following challenges need attention to ensure the continuation of the farm as a family farm in the future: corporate governance; performance measurement and compensation of family members; ownership succession; family harmony between all family members and management succession planning.

The Efficiency of Split Panel Designs in an Analysis of Variance Model

Science.gov (United States)

Wang, Wei-Guo; Liu, Hai-Jun

2016-01-01

We consider split panel design efficiency in analysis of variance models, that is, the determination of the cross-sections series optimal proportion in all samples, to minimize parametric best linear unbiased estimators of linear combination variances. An orthogonal matrix is constructed to obtain manageable expression of variances. On this basis, we derive a theorem for analyzing split panel design efficiency irrespective of interest and budget parameters. Additionally, relative estimator efficiency based on the split panel to an estimator based on a pure panel or a pure cross-section is present. The analysis shows that the gains from split panel can be quite substantial. We further consider the efficiency of split panel design, given a budget, and transform it to a constrained nonlinear integer programming. Specifically, an efficient algorithm is designed to solve the constrained nonlinear integer programming. Moreover, we combine one at time designs and factorial designs to illustrate the algorithm’s efficiency with an empirical example concerning monthly consumer expenditure on food in 1985, in the Netherlands, and the efficient ranges of the algorithm parameters are given to ensure a good solution. PMID:27163447

POST OCCUPANCY EVALUATION OF ENERGY-EFFICIENT BUILDINGS IN TROPICAL CLIMATES – MALAYSIA

Directory of Open Access Journals (Sweden)

Ban-Huat Ng

2013-07-01

Full Text Available There exists a well-known gap between occupants and building’s energy-efficient designs. A comprehensive building performance diagnostic technique, Post Occupancy Evaluation (POE may surpass the current evaluation method by reducing the gap between occupants and building’s energy-efficient design. Due to these reasons, the aim of this research is to identify the problems with respect to energy-efficient design which affect occupants’ comfort. This research focuses on the application of energy-efficient design in office building and was conducted on energy-efficient buildings in Malaysia. A building performance survey framework, Energy-efficient Building Environmental Quality Questionnaire (EBEQ2, was  used to identify the problems affecting occupants’ comfort and buildings’ Indoor Environmental Quality (IEQ. The result was analyzed using Statistical Package for Social Science (SPSS. The research outcome shows that majority of occupants are not satisfied  with the thermal comfort and lighting condition of  the buildings. Building certified with sustainable building rating tools does not guarantee better IEQ performance. Thus  continuous research is needed to ensure energy-efficient building concept is applied effectively in each type of building.

Insights on Measuring and Reporting Heterogeneous Photocatalysis: Efficiency Definitions and Setup Examples

KAUST Repository

Qureshi, Muhammad

2016-08-29

Heterogeneous photocatalysis is a potentially competitive solution for the direct production of solar fuels. This research field has seen tremendous growth over the last five decades, and with such an exciting research topic, it has seen—and will continue to see—an increasing number of papers being published in a variety of journals. However, it is becoming increasingly difficult to compare the efficiencies of heterogeneous photocatalyst powders, because different researchers report their results in different ways. Efforts have been made to create standards for reporting data in this field, but there continues to be a discrepancy in published works. This article intends to clarify efficiency definitions, and clarify misconceptions as to why researchers should avoid reporting rates of evolution per gram, per surface area of catalyst, or as turnover frequencies (TOFs) alone, to be able to compare photocatalytic efficiency among different materials. By providing an example of a photoreactor for water splitting in the authors’ laboratory, the paper also intends to guide new researchers in the field. This article does not discuss how to improve photocatalysis but rather how to improve the reporting of photocatalysis to ensure reproducibility and effective benchmarking. Researchers should not only ensure that they have all the appropriate characterization and statistical data to support their claims but should also recognize that improperly reported data may lead to faulty benchmarking that prevents their results from being compared with those of other photocatalysts, inhibiting the progress of photocatalytic research.

Insights on Measuring and Reporting Heterogeneous Photocatalysis: Efficiency Definitions and Setup Examples

KAUST Repository

Qureshi, Muhammad; Takanabe, Kazuhiro

2016-01-01

Heterogeneous photocatalysis is a potentially competitive solution for the direct production of solar fuels. This research field has seen tremendous growth over the last five decades, and with such an exciting research topic, it has seen—and will continue to see—an increasing number of papers being published in a variety of journals. However, it is becoming increasingly difficult to compare the efficiencies of heterogeneous photocatalyst powders, because different researchers report their results in different ways. Efforts have been made to create standards for reporting data in this field, but there continues to be a discrepancy in published works. This article intends to clarify efficiency definitions, and clarify misconceptions as to why researchers should avoid reporting rates of evolution per gram, per surface area of catalyst, or as turnover frequencies (TOFs) alone, to be able to compare photocatalytic efficiency among different materials. By providing an example of a photoreactor for water splitting in the authors’ laboratory, the paper also intends to guide new researchers in the field. This article does not discuss how to improve photocatalysis but rather how to improve the reporting of photocatalysis to ensure reproducibility and effective benchmarking. Researchers should not only ensure that they have all the appropriate characterization and statistical data to support their claims but should also recognize that improperly reported data may lead to faulty benchmarking that prevents their results from being compared with those of other photocatalysts, inhibiting the progress of photocatalytic research.

Computationally Efficient Chaotic Spreading Sequence Selection for Asynchronous DS-CDMA

Directory of Open Access Journals (Sweden)

Litviņenko Anna

2017-12-01

Full Text Available The choice of the spreading sequence for asynchronous direct-sequence code-division multiple-access (DS-CDMA systems plays a crucial role for the mitigation of multiple-access interference. Considering the rich dynamics of chaotic sequences, their use for spreading allows overcoming the limitations of the classical spreading sequences. However, to ensure low cross-correlation between the sequences, careful selection must be performed. This paper presents a novel exhaustive search algorithm, which allows finding sets of chaotic spreading sequences of required length with a particularly low mutual cross-correlation. The efficiency of the search is verified by simulations, which show a significant advantage compared to non-selected chaotic sequences. Moreover, the impact of sequence length on the efficiency of the selection is studied.

Commissioning of energy-efficiency measures: Costs and benefits for 16 buildings

Energy Technology Data Exchange (ETDEWEB)

Piette, M.A.; Nordman, B.; Greenberg, S.

1995-04-01

Building systems and energy-efficiency measures (EEMs) often don`t perform as well in practice as expected at the design stage. This fact has become clear to many organizations concerned with ensuring building performance. What to do about these problems is less clear. Several electric utilities around the U.S. have begun to take action to address the start-up, control, and operational problems that are found in nearly every building. One of the most beneficial periods to intervene in the building life cycle is during the start-up phase of a now building. Building commissioning during start up is such an intervention. Commissioning can be defined as: a set of procedures, responsibilities, and methods to advance a system from static installation to full working order in accordance with design intent. In broad terms, commissioning can extend from design reviews through operations and maintenance planning and training. With such a broad scope aimed at the entire building life cycle, commissioning is often likened to {open_quotes}Total Quality Management{close_quotes} Yet the heart of commissioning are the procedures developed and executed to ensure that all building systems function as intended. The incorporation of energy-efficiency criteria into building commissioning is a new development.

Radiolabelled GLP-1 receptor antagonist binds to GLP-1 receptor-expressing human tissues

Energy Technology Data Exchange (ETDEWEB)

Waser, Beatrice; Reubi, Jean Claude [University of Berne, Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, PO Box 62, Berne (Switzerland)

2014-06-15

Radiolabelled glucagon-like peptide 1 (GLP-1) receptor agonists have recently been shown to successfully image benign insulinomas in patients. For the somatostatin receptor targeting of tumours, however, it was recently reported that antagonist tracers were superior to agonist tracers. The present study therefore evaluated various forms of the {sup 125}iodinated-Bolton-Hunter (BH)-exendin(9-39) antagonist tracer for the in vitro visualization of GLP-1 receptor-expressing tissues in rats and humans and compared it with the agonist tracer {sup 125}I-GLP-1(7-36)amide. Receptor autoradiography studies with {sup 125}I-GLP-1(7-36)amide agonist or {sup 125}I-BH-exendin(9-39) antagonist radioligands were performed in human and rat tissues. The antagonist {sup 125}I-BH-exendin(9-39) labelled at lysine 19 identifies all human and rat GLP-1 target tissues and GLP-1 receptor-expressing tumours. Binding is of high affinity and is comparable in all tested tissues in its binding properties with the agonist tracer {sup 125}I-GLP-1(7-36)amide. For comparison, {sup 125}I-BH-exendin(9-39) with the BH labelled at lysine 4 did identify the GLP-1 receptor in rat tissues but not in human tissues. The GLP-1 receptor antagonist exendin(9-39) labelled with {sup 125}I-BH at lysine 19 is an excellent GLP-1 radioligand that identifies human and rat GLP-1 receptors in normal and tumoural tissues. It may therefore be the molecular basis to develop suitable GLP-1 receptor antagonist radioligands for in vivo imaging of GLP-1 receptor-expressing tissues in patients. (orig.)

Ensuring preservation of nuclear materials at RT plant storage facilities by upgrading physical protection, containment (TID) and TV surveillance measures

International Nuclear Information System (INIS)

Savin, A.A.

1999-01-01

The upgrading of nuclear material (NM) physical protection system of storage facilities for plutonium dioxide has been carried out in the frame of contract between Sandia National Laboratories and PA Mayak. The implementation of this project is of great importance for ensuring the preservation of NM in storage. The project envisages a complex approach to the solution of the task: the use of engineered fences, detection means, observation devices, access and control thereof for the personnel; the organization of security force in such way that to give a possibility to take adequate and purposeful actions towards possible adversaries. The design includes upgrading the system for physical protection through the introduction of modern, efficient engineering devices for security, integrated system for access control and security, the system for TV surveillance [ru

Dengue virus receptor

OpenAIRE

Hidari, Kazuya I.P.J.; Suzuki, Takashi

2011-01-01

Dengue virus is an arthropod-borne virus transmitted by Aedes mosquitoes. Dengue virus causes fever and hemorrhagic disorders in humans and non-human primates. Direct interaction of the virus introduced by a mosquito bite with host receptor molecule(s) is crucial for virus propagation and the pathological progression of dengue diseases. Therefore, elucidation of the molecular mechanisms underlying the interaction between dengue virus and its receptor(s) in both humans and mosquitoes is essent...

Allelic exchange of pheromones and their receptors reprograms sexual identity in Cryptococcus neoformans.

Directory of Open Access Journals (Sweden)

Brynne C Stanton

2010-02-01

Full Text Available Cell type specification is a fundamental process that all cells must carry out to ensure appropriate behaviors in response to environmental stimuli. In fungi, cell identity is critical for defining "sexes" known as mating types and is controlled by components of mating type (MAT loci. MAT-encoded genes function to define sexes via two distinct paradigms: 1 by controlling transcription of components common to both sexes, or 2 by expressing specially encoded factors (pheromones and their receptors that differ between mating types. The human fungal pathogen Cryptococcus neoformans has two mating types (a and alpha that are specified by an extremely unusual MAT locus. The complex architecture of this locus makes it impossible to predict which paradigm governs mating type. To identify the mechanism by which the C. neoformans sexes are determined, we created strains in which the pheromone and pheromone receptor from one mating type (a replaced the pheromone and pheromone receptor of the other (alpha. We discovered that these "alpha(a" cells effectively adopt a new mating type (that of a cells; they sense and respond to alpha factor, they elicit a mating response from alpha cells, and they fuse with alpha cells. In addition, alpha(a cells lose the alpha cell type-specific response to pheromone and do not form germ tubes, instead remaining spherical like a cells. Finally, we discovered that exogenous expression of the diploid/dikaryon-specific transcription factor Sxi2a could then promote complete sexual development in crosses between alpha and alpha(a strains. These data reveal that cell identity in C. neoformans is controlled fully by three kinds of MAT-encoded proteins: pheromones, pheromone receptors, and homeodomain proteins. Our findings establish the mechanisms for maintenance of distinct cell types and subsequent developmental behaviors in this unusual human fungal pathogen.

Allelic exchange of pheromones and their receptors reprograms sexual identity in Cryptococcus neoformans.

Science.gov (United States)

Stanton, Brynne C; Giles, Steven S; Staudt, Mark W; Kruzel, Emilia K; Hull, Christina M

2010-02-26

Cell type specification is a fundamental process that all cells must carry out to ensure appropriate behaviors in response to environmental stimuli. In fungi, cell identity is critical for defining "sexes" known as mating types and is controlled by components of mating type (MAT) loci. MAT-encoded genes function to define sexes via two distinct paradigms: 1) by controlling transcription of components common to both sexes, or 2) by expressing specially encoded factors (pheromones and their receptors) that differ between mating types. The human fungal pathogen Cryptococcus neoformans has two mating types (a and alpha) that are specified by an extremely unusual MAT locus. The complex architecture of this locus makes it impossible to predict which paradigm governs mating type. To identify the mechanism by which the C. neoformans sexes are determined, we created strains in which the pheromone and pheromone receptor from one mating type (a) replaced the pheromone and pheromone receptor of the other (alpha). We discovered that these "alpha(a)" cells effectively adopt a new mating type (that of a cells); they sense and respond to alpha factor, they elicit a mating response from alpha cells, and they fuse with alpha cells. In addition, alpha(a) cells lose the alpha cell type-specific response to pheromone and do not form germ tubes, instead remaining spherical like a cells. Finally, we discovered that exogenous expression of the diploid/dikaryon-specific transcription factor Sxi2a could then promote complete sexual development in crosses between alpha and alpha(a) strains. These data reveal that cell identity in C. neoformans is controlled fully by three kinds of MAT-encoded proteins: pheromones, pheromone receptors, and homeodomain proteins. Our findings establish the mechanisms for maintenance of distinct cell types and subsequent developmental behaviors in this unusual human fungal pathogen.

Repeated blockade of mineralocorticoid receptors, but not of glucocorticoid receptors impairs food rewarded spatial learning

NARCIS (Netherlands)

Douma, B. R.; Korte, S. M.; Buwalda, B.; La Fleur, S. E.; Bohus, B.; Luiten, P. G.

1998-01-01

Corticosteroids from the adrenal cortex influence a variety of behaviours including cognition, learning and memory. These hormones act via two intracellular receptors, the mineralo-corticoid receptor (MR) and the glucocorticoid receptor (GR). These two receptor types display a high concentration and

Repeated blockade of mineralocorticoid receptors, but not of glucocorticoid receptors impairs food rewarded spatial learning

NARCIS (Netherlands)

Douma, BRK; Korte, SM; Buwalda, B; la Fleur, SE; Bohus, B; Luiten, PGM

Corticosteroids from the adrenal cortex influence a variety of behaviours including cognition, learning and memory. These hormones act via two intracellular receptors, the mineralo-corticoid receptor (MR) and the glucocorticoid receptor (GR). These two receptor types display a high concentration and

Energy-efficient peer-to-peer networking for constrained-capacity mobile environments

OpenAIRE

Harjula, E. (Erkki)

2016-01-01

Abstract Energy efficiency is a powerful measure for promoting sustainability in technological evolution and ensuring feasible battery life of end-user devices in mobile computing. Peer-to-peer technology provides decentralized and self-organizing architecture for distributing content between devices in networks that scale up almost infinitely. However, peer-to-peer networking may require lots of resources from peer nodes, which in turn may lead to increased energy consumption on mobile d...

Portuguese state university performance according to students: an efficiency analysis

Directory of Open Access Journals (Sweden)

Emerson Wagner Mainardes

2016-08-01

Full Text Available The objective of this research project is to evaluate the performance of Portuguese state universities in accordance with the expectations and satisfactions of their students and through recourse to the DEA methodology and thus representing one of the very few studies analysing university performance based upon student perceptions. According to an output oriented Variable Returns to Scale model, handling the responses returned by 1,669 students, the results demonstrate that faculties generally attain a good relationship between student expectations and their levels of satisfaction. We furthermore conclude that university scale does not guarantee efficiency. Hence, irrespective of size, universities are able to ensure the satisfaction of their students. Finally, the results show that satisfying only certain expectations related to specific aspects does not prove sufficient to guaranteeing overall student satisfaction. The analysis also correspondingly finds that while some decision making units prove efficient in satisfying expectations on specific aspects, they fail to attain such efficiency in the overall perspective of students.

Photovoltaic System Regulation Based on a PID Fuzzy Controller to Ensure a Fixed Settling Time

Directory of Open Access Journals (Sweden)

Paula A. Ortiz-Valencia

2013-11-01

Full Text Available The main objective of the controllers in photovoltaic systems (PV is to ensure the maximum extraction of the available power. Those controllers usually combine the action of a maximum power point tracking algorithm (MPPT with a voltage regulator, which has the function of rejecting disturbances at the panel terminals. Such controllers are commonly based on PI and PID structures, it requiring linearized models at an operating point. But, due to disturbances generated by the environment and the load, the operating point of the system changes drastically, which hinder to obtain the desired system performance. This paper proposes to regulate the PV system using a Fuzzy PID controller, which adapts to changes in solar irradiance and load oscillations. This characteristic guarantees a constant settling time, which is required to precisely define the period of the MPPT algorithm. In the case of classical linear controllers, the period of the MPPT algorithm is set to the worst case (longest period which generates additional power losses by slowing down the tracking of the optimal operating point. Therefore, the solution proposed in this paper improves the overall system efficiency. Finally, such a solution is validated through simulations in Matlab®.

An Evaluation of Explicit Receptor Flexibility in Molecular Docking Using Molecular Dynamics and Torsion Angle Molecular Dynamics.

Science.gov (United States)

Armen, Roger S; Chen, Jianhan; Brooks, Charles L

2009-10-13

Incorporating receptor flexibility into molecular docking should improve results for flexible proteins. However, the incorporation of explicit all-atom flexibility with molecular dynamics for the entire protein chain may also introduce significant error and "noise" that could decrease docking accuracy and deteriorate the ability of a scoring function to rank native-like poses. We address this apparent paradox by comparing the success of several flexible receptor models in cross-docking and multiple receptor ensemble docking for p38α mitogen-activated protein (MAP) kinase. Explicit all-atom receptor flexibility has been incorporated into a CHARMM-based molecular docking method (CDOCKER) using both molecular dynamics (MD) and torsion angle molecular dynamics (TAMD) for the refinement of predicted protein-ligand binding geometries. These flexible receptor models have been evaluated, and the accuracy and efficiency of TAMD sampling is directly compared to MD sampling. Several flexible receptor models are compared, encompassing flexible side chains, flexible loops, multiple flexible backbone segments, and treatment of the entire chain as flexible. We find that although including side chain and some backbone flexibility is required for improved docking accuracy as expected, docking accuracy also diminishes as additional and unnecessary receptor flexibility is included into the conformational search space. Ensemble docking results demonstrate that including protein flexibility leads to to improved agreement with binding data for 227 active compounds. This comparison also demonstrates that a flexible receptor model enriches high affinity compound identification without significantly increasing the number of false positives from low affinity compounds.

Purinergic receptors and calcium signalling in human pancreatic duct cell lines

DEFF Research Database (Denmark)

Hansen, Mette R; Krabbe, Simon; Novak, Ivana

2008-01-01

pancreatic duct cell lines PANC-1 and CFPAC-1. Expression of P2 receptors was examined using RT-PCR and immunocytochemistry. Both cell lines, and also Capan-1 cells, express RNA transcripts for the following receptors: P2Y1, P2Y2, P2Y4, P2Y6, P2Y11-14 and P2X1, P2X2, P2X4, P2X5, P2X6 and P2X7. Using Fura-2...... and single-cell imaging we tested effects of various nucleotide analogues on intracellular Ca(2+) signals in PANC-1 and CFPAC-1 cells. The cell lines responded to all nucleotides with the following efficiency: UTP >or= ATP = ATPgammaS > BzATP. ATP, UTP and ATPgammaS elicited oscillatory responses. Bz...

Functional relevance of G-protein-coupled-receptor-associated proteins, exemplified by receptor-activity-modifying proteins (RAMPs).

Science.gov (United States)

Fischer, J A; Muff, R; Born, W

2002-08-01

The calcitonin (CT) receptor (CTR) and the CTR-like receptor (CRLR) are close relatives within the type II family of G-protein-coupled receptors, demonstrating sequence identity of 50%. Unlike the interaction between CT and CTR, receptors for the related hormones and neuropeptides amylin, CT-gene-related peptide (CGRP) and adrenomedullin (AM) require one of three accessory receptor-activity-modifying proteins (RAMPs) for ligand recognition. An amylin/CGRP receptor is revealed when CTR is co-expressed with RAMP1. When complexed with RAMP3, CTR interacts with amylin alone. CRLR, initially classed as an orphan receptor, is a CGRP receptor when co-expressed with RAMP1. The same receptor is specific for AM in the presence of RAMP2. Together with human RAMP3, CRLR defines an AM receptor, and with mouse RAMP3 it is a low-affinity CGRP/AM receptor. CTR-RAMP1, antagonized preferentially by salmon CT-(8-32) and not by CGRP-(8-37), and CRLR-RAMP1, antagonized by CGRP-(8-37), are two CGRP receptor isotypes. Thus amylin and CGRP interact specifically with heterodimeric complexes between CTR and RAMP1 or RAMP3, and CGRP and AM interact with complexes between CRLR and RAMP1, RAMP2 or RAMP3.

Pathophysiological consequences of receptor mistraffic: Tales from the platelet P2Y12 receptor.

Science.gov (United States)

Cunningham, Margaret R; Aungraheeta, Riyaad; Mundell, Stuart J

2017-07-05

Genetic variations in G protein-coupled receptor (GPCR) genes can disrupt receptor function in a wide variety of human genetic diseases, including platelet bleeding disorders. Platelets are critical for haemostasis with inappropriate platelet activation leading to the development of arterial thrombosis, which can result in heart attack and stroke whilst decreased platelet activity is associated with an increased risk of bleeding. GPCRs expressed on the surface of platelets play key roles in regulating platelet activity and therefore function. Receptors include purinergic receptors (P2Y 1 and P2Y 12 ), proteinase-activated receptor (PAR1 and PAR4) and thromboxane receptors (TPα), among others. Pharmacological blockade of these receptors forms a powerful therapeutic tool in the treatment and prevention of arterial thrombosis. With the advance of genomic technologies, there has been a substantial increase in the identification of naturally occurring rare and common GPCR variants. These variants include single-nucleotide polymorphisms (SNPs) and insertion or deletions that have the potential to alter GPCR expression or function. A number of defects in platelet GPCRs that disrupt receptor function have now been characterized in patients with mild bleeding disorders. This review will focus on rare, function-disrupting variants of platelet GPCRs with particular emphasis upon mutations in the P2Y 12 receptor gene that affect receptor traffic to modulate platelet function. Further this review will outline how the identification and characterization of function-disrupting GPCR mutations provides an essential link in translating our detailed understanding of receptor traffic and function in cell line studies into relevant human biological systems. Copyright © 2017. Published by Elsevier B.V.

ePedigree Traceability System for the Agricultural Food Supply Chain to Ensure Consumer Health

Directory of Open Access Journals (Sweden)

Umar Farooq

2016-08-01

Full Text Available Sustainability relies on the environmental, social and economical systems: the three pillars of sustainability. The social sustainability mostly advocates the people’s welfare, health, safety, and quality of life. In the agricultural food industry, the aspects of social sustainability, such as consumer health and safety have gained substantial attention due to the frequent cases of food-borne diseases. The food-borne diseases due to the food degradation, chemical contamination and adulteration of food products pose a serious threat to the consumer’s health, safety, and quality of life. To ensure the consumer’s health and safety, it is essential to develop an efficient system which can address these critical social issues in the food distribution networks. This research proposes an ePedigree (electronic pedigree traceability system based on the integration of RFID and sensor technology for real-time monitoring of the agricultural food to prevent the distribution of hazardous and adulterated food products. The different aspects regarding implementation of the proposed system in food chains are analyzed and a feasible integrated solution is proposed. The performance of the proposed system is evaluated and finally, a comprehensive analysis of the proposed ePedigree system’s impact on the social sustainability in terms of consumer health and safety is presented.

The receptor binding domain of MERS-CoV: The dawn of vaccine and treatment development

Directory of Open Access Journals (Sweden)

Nan Zhou

2014-03-01

Full Text Available The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV is becoming another “SARS-like” threat to the world. It has an extremely high death rate (∼50% as there is no vaccine or efficient therapeutics. The identification of the structures of both the MERS-CoV receptor binding domain (RBD and its complex with dipeptidyl peptidase 4 (DPP4, raises the hope of alleviating this currently severe situation. In this review, we examined the molecular basis of the RBD-receptor interaction to outline why/how could we use MERS-CoV RBD to develop vaccines and antiviral drugs.

Tyr721 regulates specific binding of the CSF-1 receptor kinase insert to PI 3'-kinase SH2 domains: a model for SH2-mediated receptor-target interactions.

Science.gov (United States)

Reedijk, M; Liu, X; van der Geer, P; Letwin, K; Waterfield, M D; Hunter, T; Pawson, T

1992-01-01

Efficient binding of active phosphatidylinositol (PI) 3'-kinase to the autophosphorylated macrophage colony stimulating factor receptor (CSF-1R) requires the noncatalytic kinase insert (KI) region of the receptor. To test whether this region could function independently to bind PI 3'-kinase, the isolated CSF-1R KI was expressed in Escherichia coli, and was inducibly phosphorylated on tyrosine. The tyrosine phosphorylated form of the CSF-1R KI bound PI 3'-kinase in vitro, whereas the unphosphorylated form had no binding activity. The p85 alpha subunit of PI 3'-kinase contains two Src homology (SH)2 domains, which are implicated in the interactions of signalling proteins with activated receptors. Bacterially expressed p85 alpha SH2 domains complexed in vitro with the tyrosine phosphorylated CSF-1R KI. Binding of the CSF-1R KI to PI 3'-kinase activity, and to the p85 alpha SH2 domains, required phosphorylation of Tyr721 within the KI domain, but was independent of phosphorylation at Tyr697 and Tyr706. Tyr721 was also critical for the association of activated CSF-1R with PI 3'-kinase in mammalian cells. Complex formation between the CSF-1R and PI 3'-kinase can therefore be reconstructed in vitro in a specific interaction involving the phosphorylated receptor KI and the SH2 domains of p85 alpha. Images PMID:1314163

High-level expression of human insulin receptor cDNA in mouse NIH 3T3 cells

International Nuclear Information System (INIS)

Whittaker, J.; Okamoto, A.K.; Thys, R.; Bell, G.I.; Steiner, D.F.; Hofmann, C.A.

1987-01-01

In order to develop a simple, efficient system for the high-level expression of human insulin receptors in eukaryotic cells, a full-length human kidney insulin receptor cDNA was inserted into a bovine papilloma virus vector under the control of the mouse metallothionein promoter. After transfection of mouse NIH 3T3 cells with this construct, seven cell lines expressing insulin receptors were isolated; two cell lines had more than 10 6 receptors per cell. The cell line with the highest 125 I-insulin binding (NIH 3T3 HIR3.5) had 6 x 10 6 receptors with a K/sub d/ of 10 -9 M. This level was not dependent on exposure to metals but could be increased further to 2 x 10 7 receptors per cell by addition of sodium butyrate to the culture medium. The α and β subunits had apparent molecular weights of 147,000 and 105,000, respectively (compared to 135,000 and 95,000 in IM-9 human lymphocytes), values identical to those of the α and β subunits of the insulin receptors of nontransformed NIH 3T3 cells. This size difference was due to altered carbohydrate composition, as N-glycanase digestion reduced the apparent receptor subunit size of the transfected cells and IM-9 lymphocytes to identical values. The alteration in N-linked oligosaccharide composition could not be ascribed to differences in the kinetics of posttranslational processing of the insulin receptors, which was comparable to that of other cells studied. The basal rate of glycogen synthesis in the cells overexpressing insulin receptors was increased 4- to 5-fold compared with controls. Low levels of added insulin (0.1 nM) caused a 50% increase in the rate of glycogen synthesis

Acetylcholine receptor antibody

Science.gov (United States)

... medlineplus.gov/ency/article/003576.htm Acetylcholine receptor antibody To use the sharing features on this page, please enable JavaScript. Acetylcholine receptor antibody is a protein found in the blood of ...

Ensuring the 50 year life of a fissile material container

International Nuclear Information System (INIS)

Glass, R.E.; Towne, T.L.

1997-12-01

Sandia was presented with an opportunity in 1993 to design containers for the long term storage and transport of fissile material. This program was undertaken at the direction of the US Department of Energy and in cooperation with Lawrence Livermore National Laboratory and Los Alamos National Laboratory which were tasked with developing the internal fixturing for the contents. The hardware is being supplied by Allied Signal Federal Manufacturing and Technologies, and the packaging will occur at Mason and Hangar Corporation's Pantex Plant. The unique challenge was to design a container that could be sealed with the fissile material contents; and, anytime during the next 50 years, the container could be transported with only the need for the pre-shipment leak test. This required not only a rigorous design capable of meeting the long term storage and transportation requirements, but also resulted in development of a surveillance program to ensure that the container continues to perform as designed over the 50-year life. This paper addresses the design of the container, the testing that was undertaken to demonstrate compliance with US radioactive materials transport regulations, and the surveillance program that has been initiated to ensure the 50-year performance

[{sup 11}C]-MeJDTic: a novel radioligand for {kappa}-opioid receptor positron emission tomography imaging

Energy Technology Data Exchange (ETDEWEB)

Poisnel, Geraldine; Oueslati, Farhana; Dhilly, Martine; Delamare, Jerome [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France); Perrio, Cecile [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France)], E-mail: perrio@cyceron.fr; Debruyne, Daniele [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France)], E-mail: debruyne@cyceron.fr; Barre, Louisa [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France)

2008-07-15

Introduction: Radiopharmaceuticals that can bind selectively the {kappa}-opioid receptor may present opportunities for staging clinical brain disorders and evaluating the efficiency of new therapies related to stroke, neurodegenerative diseases or opiate addiction. The N-methylated derivative of JDTic (named MeJDTic), which has been recently described as a potent and selective antagonist of {kappa}-opioid receptor in vitro, was labeled with carbon-11 and evaluated for in vivo imaging the {kappa}-opioid receptor in mice. Methods: [{sup 11}C]-MeJDTic was prepared by methylation of JDTic with [{sup 11}C]-methyl triflate. The binding of [{sup 11}C]-MeJDTic to {kappa}-opioid receptor was investigated ex vivo by biodistribution and competition studies using nonfasted male CD1 mice. Results: [{sup 11}C]-MeJDTic exhibited a high and rapid distribution in peripheral organs. The uptake was maximal in lung where the {kappa} receptor is largely expressed. [{sup 11}C]-MeJDTic rapidly crossed the blood-brain barrier and accumulated in the brain regions of interest (hypothalamus). The parent ligand remained the major radioactive compound in brain during the experiment. Chase studies with U50,488 (a {kappa} referring agonist), morphine (a {mu} agonist) and naltrindole (a {delta} antagonist) demonstrated that this uptake was the result of specific binding to the {kappa}-opioid receptor. Conclusion: These findings suggested that [{sup 11}C]-MeJDTic appeared to be a promising selective 'lead' radioligand for {kappa}-opioid receptor PET imaging.

Shape of Aquatic Animals and Their Swimming Efficiency

Directory of Open Access Journals (Sweden)

I. Nesteruk

2014-01-01

Full Text Available The best swimmers have a streamlined shape that ensures an attached flow pattern and a laminar boundary layer at rather large values of the Reynolds number. Simple expressions may be obtained for the volumetric drag coefficient of an ideal body of revolution under laminar unseparated flow conditions together with estimations of a critical value of the Reynolds number. A measure, the capacity-efficiency factor, calculated for different organisms and underwater vehicles, shows that information about animal shapes and locomotion is of utmost biological interest and could be useful to improve robot fish and underwater vehicles as well.

L-glutamate Receptor In Paramecium

Science.gov (United States)

Bernal-Martínez, Juan; Ortega-Soto, Arturo

2004-09-01

Behavioral, electrophysiological and biochemical experiments were performed in order to establish the presence of a glutamate receptor in the ciliate Paramecium. It was found that an AMPA/KA receptor is functionally expressed in Paramecium and that this receptor is immunologically and fillogenetically related to the AMPA/KA receptor present in vertebrates.

41 CFR 301-70.903 - What are our responsibilities for ensuring that Government aircraft are the most cost-effective...

Science.gov (United States)

2010-07-01

... responsibilities for ensuring that Government aircraft are the most cost-effective alternative for travel? 301-70... our responsibilities for ensuring that Government aircraft are the most cost-effective alternative for travel? To help ensure that Government aircraft are the most cost-effective alternative for travel, your...

Problems of Ensuring Complex Business Security in the Conditions of Modern Globalization

Directory of Open Access Journals (Sweden)

Anatoliy Petrovich Sterkhov

2015-12-01

Full Text Available From the viewpoint of ensuring complex business security, the relevance of the present work is associated with the rationale of multilevel hierarchical approach to the classification of security threats in the age of globalization. The specificity of the threats specific to one or another level of the economy, helps to better understand and consequently to build an effective system of ensuring complex business security. For each of the nine hierarchical levels of the economy the author identifies the main threats to the business, as well as the objects and subjects of this study. It is noted that the performance of the business in the form of a complex hierarchical system depends on the principle of specification. The author gives examples of the use of the basic principles of specification. It is noted that the decomposition of the economic system from the viewpoint of its hierarchical nature is of great importance not only to the distribution of the goals and objectives of security of business levels of the system, but their subordination corresponding to each level. The result is the development of specific recommendations and elaboration of the main directions to ensure complex business security for mega-, macro-, micro-, mini-, nano - and mesoeconomic levels. Although the priority of action in multi-level hierarchical system is directed from the upper to the lower levels, the success of the system as a whole depends on the behavior of all system components. It is stated that the interaction with the environment in business occurs mainly in the lower levels of the hierarchy. The quality system of ensuring complex business security which deals with hierarchical positions, will depend not so much on top-level elements, but on response to intervention on the part of lower level, more precisely from their total effect. In other words, the quality of the system of integrated safety management business provides organized feedbacks in the system.

Understanding the role of thiol and disulfide self-assembled DNA receptor monolayers for biosensing applications.

Science.gov (United States)

Carrascosa, Laura G; Martínez, Lidia; Huttel, Yves; Román, Elisa; Lechuga, Laura M

2010-09-01

A detailed study of the immobilization of three differently sulfur-modified DNA receptors for biosensing applications is presented. The three receptors are DNA-(CH)n-SH-, DNA-(CH)n-SS-(CH)n-DNA, and DNA-(CH)n-SS-DMTO. Nanomechanical and surface plasmon resonance biosensors and fluorescence and radiolabelling techniques were used for the experimental evaluation. The results highlight the critical role of sulfur linker type in DNA self-assembly, affecting the kinetic adsorption and spatial distribution of DNA chains within the monolayer and the extent of chemisorption and physisorption. A spacer (mercaptohexanol, MCH) is used to evaluate the relative efficiencies of chemisorption of the three receptors by analysing the extent to which MCH can remove physisorbed molecules from each type of monolayer. It is demonstrated that -SH derivatization is the most suitable for biosensing purposes as it results in densely packed monolayers with the lowest ratio of physisorbed probes.

Do receptors get pregnant too? Adrenergic receptor alterations in human pregnancy.

Science.gov (United States)

Smiley, R M; Finster, M

1996-01-01

In this review we discuss adrenergic receptor number and function during pregnancy, with emphasis on evidence that pregnancy results in specific receptor alterations from the nonpregnant state. Changes in adrenergic receptor function or distribution in vascular smooth muscle may be in part responsible for the decreased vascular responsiveness seen in human pregnancy, and the lack of the normal alterations may be a part of the syndromes of gestational hypertension, including preeclampsia-eclampsia. The onset of labor may be influenced by adrenergic modulation, and receptor or postreceptor level molecular alterations may trigger or facilitate normal or preterm labor. Human studies are emphasized when possible to assess the role of adrenergic signal transduction regulation in the physiology and pathophysiology of normal and complicated human pregnancy.

Presence of D4 dopamine receptors in human prefrontal cortex: a postmortem study Presença de receptores dopaminérgicos D4 em córtex cerebral humano: um estudo post-mortem

Directory of Open Access Journals (Sweden)

Donatella Marazziti

2007-06-01

Full Text Available OBJECTIVE: The aim of our study was to explore the presence and the distribution of D4 dopamine receptors in postmortem human prefrontal cortex, by means of the binding of [³H]YM-09151-2, an antagonist that has equal affinity for D2, D3 and D4 receptors. It was therefore necessary to devise a unique assay method in order to distinguish and detect the D4 component. METHOD: Frontal cortex samples were harvested postmortem, during autopsy sessions, from 5 subjects. In the first assay, tissue homogenates were incubated with increasing concentrations of [³H]YM-09151-2, whereas L-745870, which has a high affinity for D4 and a low affinity for D2/D3 receptors, was used as the displacer. In the second assay, raclopride, which has a high affinity for D2/D3 receptors and a low affinity for D4 receptors, was used to block D2/D3. The L-745870 (500 nM was added to both assays in order to determine the nonspecific binding. RESULTS: Our experiments revealed the presence of specific and saturable binding of [³H]YM-09151-2. The blockade of D2 and D3 receptors with raclopride ensured that the D4 receptors were labeled. The mean maximum binding capacity was 88 ± 25 fmol/mg protein, and the dissociation constant was 0.8 ± 0.4 nM. DISCUSSION AND CONCLUSIONS: Our findings, although not conclusive, suggest that the density of D4 receptors is low in the human prefrontal cortex.OBJETIVO: O objetivo deste estudo foi quantificar a presença e a distribuição de receptores dopaminérgicos do tipo 4 (D4 no córtex cerebral humano em amostras post-mortem através do bloqueio com ³H-YM-09151-2 - um antagonista com afinidade equivalente pelos receptores D2, D3 e D4 - e do desenvolvimento de um método para a detecção específica do componente D4. MÉTODO: Foram obtidas amostras de córtex cerebral de cinco cadáveres. Em um primeiro ensaio, os homogeneizados de tecido cerebral foram incubados em concentrações crescentes de ³H-YM-09151-2, enquanto que o L-745

Melatonin Receptor Genes in Vertebrates

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Hua Dong Yin

2013-05-01

Full Text Available Melatonin receptors are members of the G protein-coupled receptor (GPCR family. Three genes for melatonin receptors have been cloned. The MT1 (or Mel1a or MTNR1A and MT2 (or Mel1b or MTNR1B receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype, Mel1c (or MTNR1C, has been identified in fish, amphibians and birds. Another melatonin related orphan receptor, GPR50, which does not bind melatonin, is found exclusively in mammals. The hormone melatonin is secreted primarily by the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone acts systemically in numerous organs. In the brain, it is involved in the regulation of various neural and endocrine processes, and it readjusts the circadian pacemaker, the suprachiasmatic nucleus. This article reviews recent studies of gene organization, expression, evolution and mutations of melatonin receptor genes of vertebrates. Gene polymorphisms reveal that numerous mutations are associated with diseases and disorders. The phylogenetic analysis of receptor genes indicates that GPR50 is an outgroup to all other melatonin receptor sequences. GPR50 may have separated from a melatonin receptor ancestor before the split between MTNR1C and the MTNR1A/B ancestor.

Clinical and Genomic Crosstalk between Glucocorticoid Receptor and Estrogen Receptor α In Endometrial Cancer

Directory of Open Access Journals (Sweden)

Jeffery M. Vahrenkamp

2018-03-01

Full Text Available Summary: Steroid hormone receptors are simultaneously active in many tissues and are capable of altering each other’s function. Estrogen receptor α (ER and glucocorticoid receptor (GR are expressed in the uterus, and their ligands have opposing effects on uterine growth. In endometrial tumors with high ER expression, we surprisingly found that expression of GR is associated with poor prognosis. Dexamethasone reduced normal uterine growth in vivo; however, this growth inhibition was abolished in estrogen-induced endometrial hyperplasia. We observed low genomic-binding site overlap when ER and GR are induced with their respective ligands; however, upon simultaneous induction they co-occupy more sites. GR binding is altered significantly by estradiol with GR recruited to ER-bound loci that become more accessible upon estradiol induction. Gene expression responses to co-treatment were more similar to estradiol but with additional regulated genes. Our results suggest phenotypic and molecular interplay between ER and GR in endometrial cancer. : Estrogen receptor α (ER and glucocorticoid receptor (GR are expressed in the uterus and have differential effects on growth. Vahrenkamp et al. find that expression of both receptors is associated with poor outcome in endometrial cancer and that simultaneous induction of ER and GR leads to molecular interplay between the receptors. Keywords: estrogen receptor, glucocorticoid receptor, endometrial cancer

Deletion of the δ opioid receptor gene impairs place conditioning but preserves morphine reinforcement.

Science.gov (United States)

Le Merrer, Julie; Plaza-Zabala, Ainhoa; Del Boca, Carolina; Matifas, Audrey; Maldonado, Rafael; Kieffer, Brigitte L

2011-04-01

Converging experimental data indicate that δ opioid receptors contribute to mediate drug reinforcement processes. Whether their contribution reflects a role in the modulation of drug reward or an implication in conditioned learning, however, has not been explored. In the present study, we investigated the impact of δ receptor gene knockout on reinforced conditioned learning under several experimental paradigms. We assessed the ability of δ receptor knockout mice to form drug-context associations with either morphine (appetitive)- or lithium (aversive)-induced Pavlovian place conditioning. We also examined the efficiency of morphine to serve as a positive reinforcer in these mice and their motivation to gain drug injections, with operant intravenous self-administration under fixed and progressive ratio schedules and at two different doses. Mutant mice showed impaired place conditioning in both appetitive and aversive conditions, indicating disrupted context-drug association. In contrast, mutant animals displayed intact acquisition of morphine self-administration and reached breaking-points comparable to control subjects. Thus, reinforcing effects of morphine and motivation to obtain the drug were maintained. Collectively, the data suggest that δ receptor activity is not involved in morphine reinforcement but facilitates place conditioning. This study reveals a novel aspect of δ opioid receptor function in addiction-related behaviors. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Re-Appraisal of Estrogen Receptor Negative/Progesterone Receptor Positive (ER-/PR+) Breast Cancer Phenotype: True Subtype or Technical Artefact?

Science.gov (United States)

Foley, Niamh M; Coll, J M; Lowery, A J; Hynes, S O; Kerin, M J; Sheehan, M; Brodie, C; Sweeney, K J

2017-09-11

Expression of the ER and PR receptors is routinely quantified in breast cancer as a predictive marker of response to hormonal therapy. Accurate determination of ER and PR status is critical to the optimal selection of patients for targeted therapy. The existence of an ER-/PR+ subtype is controversial, with debate centred on whether this represents a true phenotype or a technical artefact on immunohistochemistry (IHC). The aim of this study was to investigate the true incidence and clinico-pathological features of ER-/PR+ breast cancers in a tertiary referral symptomatic breast unit. Clinico-pathological data were collected on invasive breast cancers diagnosed between 1995 and 2005. IHC for ER and PR receptors was repeated on all cases which were ER-/PR+, with the same paraffin block used for the initial diagnostic testing. Concordance between the diagnostic and repeat IHC was determined using validated testing. Complete data, including ER and PR status were available for 697 patients diagnosed during the study period. On diagnostic IHC, the immunophenotype of the breast tumours was: ER+/PR+ in 396 (57%), ER-/PR- in 157 (23%), ER+/PR- in 88 (12%) and ER-/PR+ in 56 (8.6%) patients. On repeat IHC of 48/56 ER-/PR+ tumours 45.8% were ER+/PR+, 6% were ER+/PR- and 43.7% were ER-/PR- None of the cases were confirmed to be ER-/PR+. The ER-/PR+ phenotypic breast cancer is likely to be the result of technical artefact. Prompt reassessment of patients originally assigned to this subtype who re-present with symptoms should be considered to ensure appropriate clinical management.

Heat rejection efficiency research of new energy automobile radiators

Science.gov (United States)

Ma, W. S.; Shen, W. X.; Zhang, L. W.

2018-03-01

The driving system of new energy vehicle has larger heat load than conventional engine. How to ensure the heat dissipation performance of the cooling system is the focus of the design of new energy vehicle thermal management system. In this paper, the heat dissipation efficiency of the radiator of the hybrid electric vehicle is taken as the research object, the heat dissipation efficiency of the radiator of the new energy vehicle is studied through the multi-working-condition enthalpy difference test. In this paper, the test method in the current standard QC/T 468-2010 “automobile radiator” is taken, but not limited to the test conditions specified in the standard, 5 types of automobile radiator are chosen, each of them is tested 20 times in simulated condition of different wind speed and engine inlet temperature. Finally, regression analysis is carried out for the test results, and regression equation describing the relationship of radiator heat dissipation heat dissipation efficiency air side flow rate cooling medium velocity and inlet air temperature is obtained, and the influence rule is systematically discussed.

Energy-efficient cooperative protocols for full-duplex relay channels

KAUST Repository

Khafagy, Mohammad Galal

2013-12-01

In this work, energy-efficient cooperative protocols are studied for full-duplex relaying (FDR) with loopback interference. In these protocols, relay assistance is only sought under certain conditions on the different link outages to ensure effective cooperation. Recently, an energy-efficient selective decode-And-forward protocol was proposed for FDR, and was shown to outperform existing schemes in terms of outage. Here, we propose an incremental selective decode-And-forward protocol that offers additional power savings, while keeping the same outage performance. We compare the performance of the two protocols in terms of the end-to-end signal-to-noise ratio cumulative distribution function via closed-form expressions. Finally, we corroborate our theoretical results with simulation, and show the relative relay power savings in comparison to non-selective cooperation in which the relay cooperates regardless of channel conditions. © 2013 IEEE.

Energy-efficient cooperative protocols for full-duplex relay channels

KAUST Repository

Khafagy, Mohammad Galal; Ismail, Amr; Alouini, Mohamed-Slim; Aï ssa, Sonia

2013-01-01

In this work, energy-efficient cooperative protocols are studied for full-duplex relaying (FDR) with loopback interference. In these protocols, relay assistance is only sought under certain conditions on the different link outages to ensure effective cooperation. Recently, an energy-efficient selective decode-And-forward protocol was proposed for FDR, and was shown to outperform existing schemes in terms of outage. Here, we propose an incremental selective decode-And-forward protocol that offers additional power savings, while keeping the same outage performance. We compare the performance of the two protocols in terms of the end-to-end signal-to-noise ratio cumulative distribution function via closed-form expressions. Finally, we corroborate our theoretical results with simulation, and show the relative relay power savings in comparison to non-selective cooperation in which the relay cooperates regardless of channel conditions. © 2013 IEEE.

Efficient Subgroup C Avian Sarcoma and Leukosis Virus Receptor Activity Requires the IgV Domain of the Tvc Receptor and Proper Display on the Cell Membrane▿

OpenAIRE

Munguia, Audelia; Federspiel, Mark J.

2008-01-01

We recently identified and cloned the receptor for subgroup C avian sarcoma and leukosis viruses [ASLV(C)], i.e., Tvc, a protein most closely related to mammalian butyrophilins, which are members of the immunoglobulin protein family. The extracellular domain of Tvc contains two immunoglobulin-like domains, IgV and IgC, which presumably each contain a disulfide bond important for native function of the protein. In this study, we have begun to identify the functional determinants of Tvc respons...

Unc-51 controls active zone density and protein composition by downregulating ERK signaling

OpenAIRE

Wairkar, Yogesh P.; Toda, Hirofumi; Mochizuki, Hiroaki; Furukubo-Tokunaga, Katsuo; Tomoda, Toshifumi; DiAntonio, Aaron

2009-01-01

Efficient synaptic transmission requires the apposition of neurotransmitter release sites opposite clusters of postsynaptic neurotransmitter receptors. Transmitter is released at active zones, which are composed of a large complex of proteins necessary for synaptic development and function. Many active zone proteins have been identified, but little is known of the mechanisms that ensure that each active zone receives the proper complement of proteins. Here we use a genetic analysis in Drosoph...

Development of Pathways to Achieve the SE4ALL Energy Efficiency Objective: Global and Regional Potential for Energy Efficiency Improvements

DEFF Research Database (Denmark)

Gregg, Jay Sterling; Balyk, Olexandr; Pérez, Cristian Hernán Cabrera

This study examines the three objectives of the UN Sustainable Energy for All (SE4ALL) initiative: 1. Ensure universal access to modern energy services by 2030. 2. Double the global rate of improvement in energy efficiency (from 1.3% to 2.6% annual reduction in energy intensity of GDP) by 2030. 3....... Double the share of renewable energy in global final energy from 18% to 36% by 2030. The integrated assessment model, ETSAP-TIAM, was used in this study to compare, from an economic optimization point of view, different scenarios for the development of the energy system between 2010 and 2030....... This analysis is conducted on a global and regional scale. The scenarios were constructed to analyze the effect of achieving the SE4ALL energy efficiency objective, the SE4ALL renewable energy objective, both together, and all three SE4ALL objectives. Synergies exist between renewable energy and energy...

Efficient heating of a swimming pool. High-efficiency boiler and solar system at Blaubeuren; Effiziente Freibad-Beheizung. Brennwert-Solartechnik in Blaubeuren

Energy Technology Data Exchange (ETDEWEB)

Trobisch, Jens [Bosch Thermotechnik GmbH, Wernau (Germany)

2009-07-01

The ''Blautopf'' karst spring near Blaubeuren is a wonder of nature and widely known even across the borders of Baden-Wuerttemberg. Few visitors, however, are aware that just a few steps away, there is another tourist attraction, i.e. the town's new outdoor swimming pool. In May 2008, a modern gas-fuelled high-efficiency boiler combined with a solar system was installed to heat the shower water for about 60,000 visitors per year. Optimised control ensures energy savings of up to 75 percent. The first season was highly successful. (orig.)

Proposal for the Evaluation of Eco-Efficient Concrete

Directory of Open Access Journals (Sweden)

Taehyoung Kim

2016-07-01

Full Text Available The importance of environmental consequences due to diverse substances that are emitted during the production of concrete is recognized, but environmental performance tends to be evaluated separately from the economic performance and durability performance of concrete. In order to evaluate concrete from the perspective of sustainable development, evaluation technologies are required for comprehensive assessment of environmental performance, economic performance, and durability performance based on a concept of sustainable development called the triple bottom line (TBL. Herein, an assessment method for concrete eco-efficiency is developed as a technique to ensure the manufacture of highly durable and eco-friendly concrete, while minimizing both the load on the ecological environment and manufacturing costs. The assessment method is based on environmental impact, manufacturing costs, and the service life of concrete. According to our findings, eco-efficiency increased as the compressive strength of concrete increased from 21 MPa to 40 MPa. The eco-efficiency of 40 MPa concrete was about 50% higher than the eco-efficiency of 24 MPa concrete. Thus eco-efficiency is found to increase with an increasing compressive strength of concrete because the rate of increase in the service life of concrete is larger than the rate of increase in the costs. In addition, eco-efficiency (KRW/year was shown to increase for all concrete strengths as mixing rates of admixtures (Ground Granulated Blast furnace Slag increased to 30% during concrete mix design. However, when the mixing rate of admixtures increased to 40% and 60%, the eco-efficiency dropped due to rapid reduction in the service life values of concrete to 74 (year/m3 and 44 (year/m3, respectively.