WorldWideScience

Sample records for conserved molecular switch

  1. Molecular Rotors as Switches

    Directory of Open Access Journals (Sweden)

    Kang L. Wang

    2012-08-01

    Full Text Available The use of a functional molecular unit acting as a state variable provides an attractive alternative for the next generations of nanoscale electronics. It may help overcome the limits of conventional MOSFETd due to their potential scalability, low-cost, low variability, and highly integratable characteristics as well as the capability to exploit bottom-up self-assembly processes. This bottom-up construction and the operation of nanoscale machines/devices, in which the molecular motion can be controlled to perform functions, have been studied for their functionalities. Being triggered by external stimuli such as light, electricity or chemical reagents, these devices have shown various functions including those of diodes, rectifiers, memories, resonant tunnel junctions and single settable molecular switches that can be electronically configured for logic gates. Molecule-specific electronic switching has also been reported for several of these device structures, including nanopores containing oligo(phenylene ethynylene monolayers, and planar junctions incorporating rotaxane and catenane monolayers for the construction and operation of complex molecular machines. A specific electrically driven surface mounted molecular rotor is described in detail in this review. The rotor is comprised of a monolayer of redox-active ligated copper compounds sandwiched between a gold electrode and a highly-doped P+ Si. This electrically driven sandwich-type monolayer molecular rotor device showed an on/off ratio of approximately 104, a read window of about 2.5 V, and a retention time of greater than 104 s. The rotation speed of this type of molecular rotor has been reported to be in the picosecond timescale, which provides a potential of high switching speed applications. Current-voltage spectroscopy (I-V revealed a temperature-dependent negative differential resistance (NDR associated with the device. The analysis of the device

  2. EDITORIAL: Molecular switches at surfaces Molecular switches at surfaces

    Science.gov (United States)

    Weinelt, Martin; von Oppen, Felix

    2012-10-01

    In nature, molecules exploit interaction with their environment to realize complex functionalities on the nanometer length scale. Physical, chemical and/or biological specificity is frequently achieved by the switching of molecules between microscopically different states. Paradigmatic examples are the energy production in proton pumps of bacteria or the signal conversion in human vision, which rely on switching molecules between different configurations or conformations by external stimuli. The remarkable reproducibility and unparalleled fatigue resistance of these natural processes makes it highly desirable to emulate nature and develop artificial systems with molecular functionalities. A promising avenue towards this goal is to anchor the molecular switches at surfaces, offering new pathways to control their functional properties, to apply electrical contacts, or to integrate switches into larger systems. Anchoring at surfaces allows one to access the full range from individual molecular switches to self-assembled monolayers of well-defined geometry and to customize the coupling between molecules and substrate or between adsorbed molecules. Progress in this field requires both synthesis and preparation of appropriate molecular systems and control over suitable external stimuli, such as light, heat, or electrical currents. To optimize switching and generate function, it is essential to unravel the geometric structure, the electronic properties and the dynamic interactions of the molecular switches on surfaces. This special section, Molecular Switches at Surfaces, collects 17 contributions describing different aspects of this research field. They analyze elementary processes, both in single molecules and in ensembles of molecules, which involve molecular switching and concomitant changes of optical, electronic, or magnetic properties. Two topical reviews summarize the current status, including both challenges and achievements in the field of molecular switches on

  3. A Novel Molecular Switch

    Science.gov (United States)

    Daber, Robert; Lewis, Mitchell

    2009-01-01

    Transcriptional regulation is a fundamental process for regulating the flux of all metabolic pathways. For the last several decades, the lac operon has served as a valuable model for studying transcription. More recently, the switch that controls the operon has also been successfully adapted to function in mammalian cells. Here we describe how, using directed evolution, we have created a novel switch that recognizes an asymmetric operator sequence. The new switch has a repressor with altered headpiece domains for operator recognition, and a redesigned dimer interface to create a heterodimeric repressor. Quite unexpectedly, the heterodimeric switch functions better than the natural system. It can repress more tightly than the naturally occurring switch of the lac operon; it is less leaky and can be induced more efficiently. Ultimately these novel repressors could be evolved to recognize eukaryotic promoters and used to regulate gene expression in mammalian systems. PMID:19540845

  4. Molecular contributions to conservation

    Science.gov (United States)

    Haig, Susan M.

    1998-01-01

    Recent advances in molecular technology have opened a new chapter in species conservation efforts, as well as population biology. DNA sequencing, MHC (major histocompatibility complex), minisatellite, microsatellite, and RAPD (random amplified polymorphic DNA) procedures allow for identification of parentage, more distant relatives, founders to new populations, unidentified individuals, population structure, effective population size, population-specific markers, etc. PCR (polymerase chain reaction) amplification of mitochondrial DNA, nuclear DNA, ribosomal DNA, chloroplast DNA, and other systems provide for more sophisticated analyses of metapopulation structure, hybridization events, and delineation of species, subspecies, and races, all of which aid in setting species recovery priorities. Each technique can be powerful in its own right but is most credible when used in conjunction with other molecular techniques and, most importantly, with ecological and demographic data collected from the field. Surprisingly few taxa of concern have been assayed with any molecular technique. Thus, rather than showcasing exhaustive details from a few well-known examples, this paper attempts to present a broad range of cases in which molecular techniques have been used to provide insight into conservation efforts.

  5. Molecular DNA switches and DNA chips

    Science.gov (United States)

    Sabanayagam, Chandran R.; Berkey, Cristin; Lavi, Uri; Cantor, Charles R.; Smith, Cassandra L.

    1999-06-01

    We present an assay to detect single-nucleotide polymorphisms on a chip using molecular DNA switches and isothermal rolling- circle amplification. The basic principle behind the switch is an allele-specific oligonucleotide circularization, mediated by DNA ligase. A DNA switch is closed when perfect hybridization between the probe oligonucleotide and target DNA allows ligase to covalently circularize the probe. Mismatches around the ligation site prevent probe circularization, resulting in an open switch. DNA polymerase is then used to preferentially amplify the closed switches, via rolling-circle amplification. The stringency of the molecular switches yields 102 - 103 fold discrimination between matched and mismatched sequences.

  6. Molecular switches and motors on surfaces.

    Science.gov (United States)

    Pathem, Bala Krishna; Claridge, Shelley A; Zheng, Yue Bing; Weiss, Paul S

    2013-01-01

    Molecular switches and motors respond structurally, electronically, optically, and/or mechanically to external stimuli, testing and potentially enabling extreme miniaturization of optoelectronic devices, nanoelectromechanical systems, and medical devices. The assembly of motors and switches on surfaces makes it possible both to measure the properties of individual molecules as they relate to their environment and to couple function between assembled molecules. In this review, we discuss recent progress in assembling molecular switches and motors on surfaces, measuring static and dynamic structures, understanding switching mechanisms, and constructing functional molecular materials and devices. As demonstrative examples, we choose a representative molecule from three commonly studied classes including molecular switches, photochromic molecules, and mechanically interlocked molecules. We conclude by offering perspectives on the future of molecular switches and motors on surfaces.

  7. Chiroptical Molecular Switches 1; Principles and Syntheses.

    NARCIS (Netherlands)

    Lange, Ben de; Jager, Wolter F.; Feringa, Bernard

    1992-01-01

    The concept and the synthesis of the basic molecules for a chiroptical molecular switch are described. This molecular switch is based on photochemical interconversion of two bistable forms of chiral sterically overcrowded olefins. A large variety of these alkenes with different properties have been

  8. Fine tuning of molecular rotor function in photochemical molecular switches

    NARCIS (Netherlands)

    ter Wiel, Matthijs K. J.; Feringa, Ben L.

    2009-01-01

    Molecular switches are used as scaffolds for the construction of controlled molecular rotors. The internal position of the switching entity in the molecule controls the dynamic behaviour of the rotor moiety in the molecule. Six new molecular motors with o-xylyl rotor moieties were prepared on the ba

  9. A nanoplasmonic switch based on molecular machines

    KAUST Repository

    Zheng, Yue Bing

    2009-06-01

    We aim to develop a molecular-machine-driven nanoplasmonic switch for its use in future nanophotonic integrated circuits (ICs) that have applications in optical communication, information processing, biological and chemical sensing. Experimental data show that an Au nanodisk array, coated with rotaxane molecular machines, switches its localized surface plasmon resonances (LSPR) reversibly when it is exposed to chemical oxidants and reductants. Conversely, bare Au nanodisks and disks coated with mechanically inert control compounds, do not display the same switching behavior. Along with calculations based on time-dependent density functional theory (TDDFT), these observations suggest that the nanoscale movements within surface-bound "molecular machines" can be used as the active components in plasmonic devices. ©2009 IEEE.

  10. In Control of Motion : From Molecular Switches to Molecular Motors

    NARCIS (Netherlands)

    Feringa, Bernard

    2001-01-01

    The design of molecular systems in which controlled linear and rotary motion can be achieved under the influence of an external signal is a major endeavor toward future nanoscale machinery. In this Account we describe the development of molecular switches and the discoveries that culminated in the

  11. Active Molecular Plasmonics: Controlling Plasmon Resonances with Molecular Switches

    KAUST Repository

    Zheng, Yue Bing

    2009-02-11

    A gold nanodisk array, coated with bistable, redox-controllable [2]rotaxane molecules, when exposed to chemical oxidants and reductants, undergoes switching of its plasmonic properties reversibly. By contrast, (i) bare gold nanodisks and (ii) disks coated with a redox-active, but mechanically inert, control compound do not display surface-plasmon-based switching. Along with calculations based on time-dependent density functional theory, these experimental observations suggest that the nanoscale movements within surface-bound “molecular machines” can be used as the active components in plasmonic devices.

  12. The Art of Building Small : From Molecular Switches to Molecular Motors

    NARCIS (Netherlands)

    Feringa, Bernard

    2007-01-01

    Molecular switches and motors are essential components of artificial molecular machines. In this perspective, we discuss progress in our design, synthesis, and functioning of photochemical and electrochemical switches and chemical and light-driven molecular motors. Special emphasis is given to the c

  13. The art of building small : From molecular switches to molecular motors

    NARCIS (Netherlands)

    Feringa, Ben L.

    2007-01-01

    Molecular switches and motors are essential components of artificial molecular machines. In this perspective, we discuss progress in our design, synthesis, and functioning of photochemical and electrochemical switches and chemical and light-driven molecular motors. Special emphasis is given to the c

  14. The art of building small : From molecular switches to molecular motors

    NARCIS (Netherlands)

    Feringa, Ben L.

    2007-01-01

    Molecular switches and motors are essential components of artificial molecular machines. In this perspective, we discuss progress in our design, synthesis, and functioning of photochemical and electrochemical switches and chemical and light-driven molecular motors. Special emphasis is given to the

  15. The Art of Building Small : From Molecular Switches to Molecular Motors

    NARCIS (Netherlands)

    Feringa, Bernard

    2007-01-01

    Molecular switches and motors are essential components of artificial molecular machines. In this perspective, we discuss progress in our design, synthesis, and functioning of photochemical and electrochemical switches and chemical and light-driven molecular motors. Special emphasis is given to the

  16. Tetrapodal molecular switches and motors: synthesis and photochemistry.

    Science.gov (United States)

    Chen, Kuang-Yen; Wezenberg, Sander J; Carroll, Gregory T; London, Gábor; Kistemaker, Jos C M; Pijper, Thomas C; Feringa, Ben L

    2014-08-01

    The design, synthesis, and dynamic behavior of a series of novel tetrapodal molecular switches and motors containing common functional groups for attachment to various inorganic and organic surfaces are presented. Using a Diels-Alder reaction, an anthracene unit with four functionalized alkyl substituents ("legs") was coupled to maleimide-functionalized molecular switches or motors under ambient conditions. Terminal functional groups at the "legs" include thioacetates and azides, making these switches and motors ideal candidates for attachment to metallic or alkyne-functionalized surfaces. UV/vis absorption spectroscopy shows that the molecular switches and motors retain their ability to undergo reversible photoinduced and/or thermally induced structural changes after attachment to the tetrapodal anthracene.

  17. Electronic transport properties of a quinone-based molecular switch

    Science.gov (United States)

    Zheng, Ya-Peng; Bian, Bao-An; Yuan, Pei-Pei

    2016-09-01

    In this paper, we carried out first-principles calculations based on density functional theory and non-equilibrium Green's function to investigate the electronic transport properties of a quinone-based molecule sandwiched between two Au electrodes. The molecular switch can be reversibly switched between the reduced hydroquinone (HQ) and oxidized quinone (Q) states via redox reactions. The switching behavior of two forms is analyzed through their I- V curves, transmission spectra and molecular projected self-consistent Hamiltonian at zero bias. Then we discuss the transmission spectra of the HQ and Q forms at different bias, and explain the oscillation of current according to the transmission eigenstates of LUMO energy level for Q form. The results suggest that this kind of a quinone-based molecule is usable as one of the good candidates for redox-controlled molecular switches.

  18. Polymer Alignment Behavior with Molecular Switching of Ferroelectric Liquid Crystal

    Science.gov (United States)

    Murashige, Takeshi; Fujikake, Hideo; Sato, Hiroto; Kikuchi, Hiroshi; Kurita, Taiichiro; Sato, Fumio

    2007-01-01

    This paper describes the molecular alignment behavior of polymer networks with switching of a ferroelectric liquid crystal (FLC) in a molecularly aligned FLC/polymer composite film. The polymer alignment in the composite film, which was slowly formed by photopolymerization-induced phase separation of a heated nematic-phase solution of FLC and monomers, was observed by polarization Raman spectral microscopy. Raman peak intensities originating from the polymers were changed with those from the FLC, when the applied voltage polarity was changed. The trace patterns of the Raman peak intensity with in-plane rotation of the composite film indicated that the formed flexible polymers can follow FLC molecular switching.

  19. Synthetic light-activated molecular switches and motors on surfaces

    NARCIS (Netherlands)

    Katsonis, Nathalie; Lubomska, Monika; Pollard, Michael M.; Feringa, Ben L.; Rudolf, Petra

    2007-01-01

    Recent advances in synthetic methods and analysis techniques provide a basis for the construction and characterization of organized arrays of molecular switches and motors on surfaces. Among them, molecular systems that can be controlled by light are particularly promising because of their ease of a

  20. Molecular magnetic switch for a metallofullerene

    OpenAIRE

    Bo WU; Wang, Taishan; Feng, Yongqiang; Zhang, Zhuxia; Jiang,Li; Wang, Chunru

    2015-01-01

    The endohedral fullerenes lead to well-protected internal species by the fullerene cages, and even highly reactive radicals can be stabilized. However, the manipulation of the magnetic properties of these radicals from outside remains challenging. Here we report a system of a paramagnetic metallofullerene Sc3C2@C80 connected to a nitroxide radical, to achieve the remote control of the magnetic properties of the metallofullerene. The remote nitroxide group serves as a magnetic switch for the e...

  1. Molecular magnetic switch for a metallofullerene

    Science.gov (United States)

    Wu, Bo; Wang, Taishan; Feng, Yongqiang; Zhang, Zhuxia; Jiang, Li; Wang, Chunru

    2015-01-01

    The endohedral fullerenes lead to well-protected internal species by the fullerene cages, and even highly reactive radicals can be stabilized. However, the manipulation of the magnetic properties of these radicals from outside remains challenging. Here we report a system of a paramagnetic metallofullerene Sc3C2@C80 connected to a nitroxide radical, to achieve the remote control of the magnetic properties of the metallofullerene. The remote nitroxide group serves as a magnetic switch for the electronic spin resonance (ESR) signals of Sc3C2@C80 via spin–spin interactions. Briefly, the nitroxide radical group can ‘switch off’ the ESR signals of the Sc3C2@C80 moiety. Moreover, the strength of spin–spin interactions between Sc3C2@C80 and the nitroxide group can be manipulated by changing the distance between these two spin centres. In addition, the ESR signals of the Sc3C2@C80 moiety can be switched on at low temperatures through weakened spin–lattice interactions. PMID:25732144

  2. Phosphorylation: The Molecular Switch of Double-Strand Break Repair

    Directory of Open Access Journals (Sweden)

    K. C. Summers

    2011-01-01

    Full Text Available Repair of double-stranded breaks (DSBs is vital to maintaining genomic stability. In mammalian cells, DSBs are resolved in one of the following complex repair pathways: nonhomologous end-joining (NHEJ, homologous recombination (HR, or the inclusive DNA damage response (DDR. These repair pathways rely on factors that utilize reversible phosphorylation of proteins as molecular switches to regulate DNA repair. Many of these molecular switches overlap and play key roles in multiple pathways. For example, the NHEJ pathway and the DDR both utilize DNA-PK phosphorylation, whereas the HR pathway mediates repair with phosphorylation of RPA2, BRCA1, and BRCA2. Also, the DDR pathway utilizes the kinases ATM and ATR, as well as the phosphorylation of H2AX and MDC1. Together, these molecular switches regulate repair of DSBs by aiding in DSB recognition, pathway initiation, recruitment of repair factors, and the maintenance of repair mechanisms.

  3. Monitoring Gene Expression In Vivo with Nucleic Acid Molecular Switches

    Energy Technology Data Exchange (ETDEWEB)

    David C. Ward; Patricia Bray-Ward

    2005-01-26

    The overall objectives of this project were (1) to develop allosteric ribozymes capable of acting as molecular switches for monitoring the levels of both wild-type and mutant mRNA species in living cells and whole animals and (2) to develop highly efficient reagents to deliver nucleic acid molecular switches into living cells, tissues and animals with the ultimate goal of expression profiling specific mRNAs of diagnostic or prognostic value within tumors in animals. During the past year, we have moved our laboratory to Nevada and in the moving process we have lost electronic and paper copies of prior progress reports concerning the construction and biological properties of the molecular switches. Since there was minimal progress during the last year on molecular switches, we are relying on past project reports to provide a summary of our data on this facet of the grant. Here we are summarizing the work done on the delivery reagents and their application to inducing mutations in living cells, which will include work done during the no cost extension.

  4. Heparan sulfate regulates ADAM12 through a molecular switch mechanism

    DEFF Research Database (Denmark)

    Sørensen, Hans P; Vives, Romain R; Manetopoulos, Christina

    2008-01-01

    tumor progression and chondrocyte proliferation in osteoarthritic cartilage, is shown to possess a pro/catalytic domain cationic molecular switch, regulated by exogenous heparan sulfate and heparin but also endogenous cell surface proteoglycans and the polyanion, calcium pentosan polysulfate. Sheddase...... functions of ADAM12 are regulated by the switch, as are proteolytic functions in placental tissue and sera of pregnant women. Moreover, human heparanase, an enzyme also linked to tumorigenesis, can promote ADAM12 sheddase activity at the cell surface through cleavage of the inhibitory heparan sulfate...

  5. Ultrafast isomerization in a difluoroboryl-coordinated molecular switch

    Science.gov (United States)

    Consani, Cristina; Berberich, Martin; Würthner, Frank; Brixner, Tobias

    2017-09-01

    Molecular switches based on light-induced isomerization cycles are promising materials for sensors and biomedical applications. Understanding the details of the isomerization photocycle and identifying the nuclear coordinates involved in the photoreaction are relevant topics. Here we characterize the cis → trans and trans → cis isomerization of a new type of BF2-coordinated azo-dye molecular switch by pump-probe spectroscopy. While cis → trans isomerization is ultrafast and proceeds via a conical intersection, the trans → cis photocycle is more complex and involves at least three reaction channels. Finally, we employ the vibrational wavepackets accompanying isomerization to infer information on the nuclear degrees of freedom involved in the photoreaction.

  6. Dissipation enhanced vibrational sensing in an olfactory molecular switch

    Energy Technology Data Exchange (ETDEWEB)

    Chęcińska, Agata; Heaney, Libby [Centre for Quantum Technologies, National University of Singapore, Singapore 117543 (Singapore); Pollock, Felix A. [Atomic and Laser Physics, Clarendon Laboratory, University of Oxford, Parks Road, Oxford OX1 3PU (United Kingdom); Nazir, Ahsan [Photon Science Institute and School of Physics and Astronomy, University of Manchester, Oxford Road, Manchester M13 9PL (United Kingdom); Centre for Quantum Dynamics, Imperial College London, London SW7 2AZ (United Kingdom)

    2015-01-14

    Motivated by a proposed olfactory mechanism based on a vibrationally activated molecular switch, we study electron transport within a donor-acceptor pair that is coupled to a vibrational mode and embedded in a surrounding environment. We derive a polaron master equation with which we study the dynamics of both the electronic and vibrational degrees of freedom beyond previously employed semiclassical (Marcus-Jortner) rate analyses. We show (i) that in the absence of explicit dissipation of the vibrational mode, the semiclassical approach is generally unable to capture the dynamics predicted by our master equation due to both its assumption of one-way (exponential) electron transfer from donor to acceptor and its neglect of the spectral details of the environment; (ii) that by additionally allowing strong dissipation to act on the odorant vibrational mode, we can recover exponential electron transfer, though typically at a rate that differs from that given by the Marcus-Jortner expression; (iii) that the ability of the molecular switch to discriminate between the presence and absence of the odorant, and its sensitivity to the odorant vibrational frequency, is enhanced significantly in this strong dissipation regime, when compared to the case without mode dissipation; and (iv) that details of the environment absent from previous Marcus-Jortner analyses can also dramatically alter the sensitivity of the molecular switch, in particular, allowing its frequency resolution to be improved. Our results thus demonstrate the constructive role dissipation can play in facilitating sensitive and selective operation in molecular switch devices, as well as the inadequacy of semiclassical rate equations in analysing such behaviour over a wide range of parameters.

  7. Network switching strategy for energy conservation in heterogeneous networks.

    Science.gov (United States)

    Song, Yujae; Choi, Wooyeol; Baek, Seungjae

    2017-01-01

    In heterogeneous networks (HetNets), the large-scale deployment of small base stations (BSs) together with traditional macro BSs is an economical and efficient solution that is employed to address the exponential growth in mobile data traffic. In dense HetNets, network switching, i.e., handovers, plays a critical role in connecting a mobile terminal (MT) to the best of all accessible networks. In the existing literature, a handover decision is made using various handover metrics such as the signal-to-noise ratio, data rate, and movement speed. However, there are few studies on handovers that focus on energy efficiency in HetNets. In this paper, we propose a handover strategy that helps to minimize energy consumption at BSs in HetNets without compromising the quality of service (QoS) of each MT. The proposed handover strategy aims to capture the effect of the stochastic behavior of handover parameters and the expected energy consumption due to handover execution when making a handover decision. To identify the validity of the proposed handover strategy, we formulate a handover problem as a constrained Markov decision process (CMDP), by which the effects of the stochastic behaviors of handover parameters and consequential handover energy consumption can be accurately reflected when making a handover decision. In the CMDP, the aim is to minimize the energy consumption to service an MT over the lifetime of its connection, and the constraint is to guarantee the QoS requirements of the MT given in terms of the transmission delay and call-dropping probability. We find an optimal policy for the CMDP using a combination of the Lagrangian method and value iteration. Simulation results verify the validity of the proposed handover strategy.

  8. Network switching strategy for energy conservation in heterogeneous networks

    Science.gov (United States)

    Song, Yujae; Choi, Wooyeol; Baek, Seungjae

    2017-01-01

    In heterogeneous networks (HetNets), the large-scale deployment of small base stations (BSs) together with traditional macro BSs is an economical and efficient solution that is employed to address the exponential growth in mobile data traffic. In dense HetNets, network switching, i.e., handovers, plays a critical role in connecting a mobile terminal (MT) to the best of all accessible networks. In the existing literature, a handover decision is made using various handover metrics such as the signal-to-noise ratio, data rate, and movement speed. However, there are few studies on handovers that focus on energy efficiency in HetNets. In this paper, we propose a handover strategy that helps to minimize energy consumption at BSs in HetNets without compromising the quality of service (QoS) of each MT. The proposed handover strategy aims to capture the effect of the stochastic behavior of handover parameters and the expected energy consumption due to handover execution when making a handover decision. To identify the validity of the proposed handover strategy, we formulate a handover problem as a constrained Markov decision process (CMDP), by which the effects of the stochastic behaviors of handover parameters and consequential handover energy consumption can be accurately reflected when making a handover decision. In the CMDP, the aim is to minimize the energy consumption to service an MT over the lifetime of its connection, and the constraint is to guarantee the QoS requirements of the MT given in terms of the transmission delay and call-dropping probability. We find an optimal policy for the CMDP using a combination of the Lagrangian method and value iteration. Simulation results verify the validity of the proposed handover strategy. PMID:28241083

  9. Molecular mechanism of 7TM receptor activation--a global toggle switch model

    DEFF Research Database (Denmark)

    Schwartz, Thue W; Frimurer, Thomas M; Holst, Birgitte;

    2006-01-01

    The multitude of chemically highly different agonists for 7TM receptors apparently do not share a common binding mode or active site but nevertheless act through induction of a common molecular activation mechanism. A global toggle switch model is proposed for this activation mechanism to reconcile...... to this model, a vertical see-saw movement of TM-VI-and to some degree TM-VII-around a pivot corresponding to the highly conserved prolines will occur during receptor activation, which may involve the outer segment of TM-V in an as yet unclear fashion. Small-molecule agonists can stabilize such a proposed...

  10. Dynamic signaling cascades: reversible covalent reaction-coupled molecular switches.

    Science.gov (United States)

    Ren, Yulong; You, Lei

    2015-11-11

    The research of systems chemistry exploring complex mixtures of interacting synthetic molecules has been burgeoning recently. Herein we demonstrate for the first time the coupling of molecular switches with a dynamic covalent reaction (DCR) and the modulation of created chemical cascades with a variety of inputs, thus closely mimicking a biological signaling system. A novel Michael type DCR of 10-methylacridinium perchlorate and monothiols exhibiting excellent regioselectivity and tunable affinity was discovered. A delicate balance between the unique reactivity of the reactant and the stability of the adduct leads to the generation of a strong acid in a thermodynamically controlled system. The dynamic cascade was next created via coupling of the DCR and a protonation-induced configurational switch (E/Z isomerization) through a proton relay. Detailed examination of the interdependence of the equilibrium enabled us to rationally optimize the cascade and also shed light on the possible intermediate of the switching process. Furthermore, relative independence of the coupled reactions was verified by the identification of stimuli that are able to facilitate one reaction but suppress the other. To further enhance systematic complexity, a second DCR of electrophilic aldehydes and thiols was employed for the reversible inhibition of the binary system, thus achieving the interplay of multiple equilibria. Finally, a fluorescence switch was turned on through coupling with the DCR, showcasing the versatility of our strategy. The results described herein should pave the way for the exploitation of multifunctional dynamic covalent cascades.

  11. Molecular switching analyzed with sub-molecular precision: CuPc on Cu(111)

    Energy Technology Data Exchange (ETDEWEB)

    Schaffert, Johannes; Cottin, Maren; Sonntag, Andreas; Karacuban, Hatice; Bobisch, Christian; Moeller, Rolf [Faculty of Physics, Center for Nanointegration Duisburg-Essen, University of Duisburg-Essen, 47048 Duisburg (Germany); Lorente, Nicolas [Centro de Investigacion en Nanociencia y Nanotecnologia, Campus de la Universitat Autonoma de Barcelona, 08193 Bellaterra (Spain)

    2011-07-01

    The current fluctuations in Scanning Tunneling Microscopy and Spectroscopy have been analyzed in real time using special analogue electronics. This type of Scanning Action Microscopy technique allows to map topography and switching processes simultaneously. For the Cu-Phthalocyanine (CuPc) molecule on Cu(111), switching between two states is observed. The switching frequency, the switching amplitude and the ratio between the residence times in the observed states can be studied with Angstrom spacial resolution. Spectroscopic data obtained at 7 K yields information about the involved electronic states. Based on the experimental data as well as DFT calculations a model is presented. The CuPc molecule switches between different adsorption configurations, which are attributed to different angles of molecular rotation on the Cu(111) surface.

  12. The Design and Measurement of Molecular Electronic Switches and Memories

    Science.gov (United States)

    Reed, Mark

    2000-03-01

    Electron transport studies in molecular-scale systems have recently become possible with the utilization of advanced microfabrication and self-assembly techniques. We have performed the measurement of the conductance of a single molecule using a break junction technique [1], the demonstration of molecular diodes [2], and the systematic investigation of metal-molecule contacts in a variety of systems [3]. Most recently, we have observed [4] large and useful reversible switching behavior in an electronic device that utilizes molecules as the active component, specifically a nitroamine redox center. The molecular device exhibits negative differential resistance (NDR) and peak-to-valley ratios exceeding 1000:1 and exceeds that observed in typical solid state quantum well resonant tunneling heterostructures. The designs of molecular switches, memories, and their circuit applications will be discussed. 1. M. A. Reed et al., Science 278, 252 (1997). 2. C. Zhou et al., Appl. Phys. Lett. 71, 611 (1997). 3. J. Chen et al., Chem Phys Lett 313, 741 (1999). 4. J. Chen et al., Science 286, 1550 (1999).

  13. Amphibian molecular ecology and how it has informed conservation.

    Science.gov (United States)

    McCartney-Melstad, Evan; Shaffer, H Bradley

    2015-10-01

    Molecular ecology has become one of the key tools in the modern conservationist's kit. Here we review three areas where molecular ecology has been applied to amphibian conservation: genes on landscapes, within-population processes, and genes that matter. We summarize relevant analytical methods, recent important studies from the amphibian literature, and conservation implications for each section. Finally, we include five in-depth examples of how molecular ecology has been successfully applied to specific amphibian systems. © 2015 John Wiley & Sons Ltd.

  14. Benchmark Performance of Global Switching versus Local Switching for Trajectory Surface Hopping Molecular Dynamics Simulation: Cis↔Trans Azobenzene Photoisomerization.

    Science.gov (United States)

    Yue, Ling; Yu, Le; Xu, Chao; Lei, Yibo; Liu, Yajun; Zhu, Chaoyuan

    2017-05-19

    A newly developed global switching algorithm that does not require calculation of nonadiabatic coupling vectors reduces computational costs significantly. However, the accuracy of this simplest nonadiabatic molecular dynamic method has not been extensively compared with the conventional Tully's fewest switches. It is necessary to demonstrate the accuracy of this global switching algorithm. An extensive comparison between local and global switching on-the-fly trajectory surface hopping molecular dynamics is performed for cis-to-trans (800 sampling trajectories) and trans-to-cis (600 sampling trajectories) azobenzene photoisomerization at the OM2/MRCI level. The global switching algorithm is coded into the Newton-X program package. Excellent agreement between the two switching algorithms is obtained not only for highly averaged quantities of quantum yields and lifetimes, but also for detailed contour patterns of product distributions, hopping spot distributions and hopping directions in terms of conical intersections between ground and the first excited states. Therefore, the global switching trajectory surface hopping method can be applied to larger complex systems in which nonadiabatic coupling is not available for excited-state molecular dynamic simulations. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Energy conservation in molecular dynamics simulations of classical systems

    DEFF Research Database (Denmark)

    Toxværd, Søren; Heilmann, Ole; Dyre, J. C.

    2012-01-01

    Classical Newtonian dynamics is analytic and the energy of an isolated system is conserved. The energy of such a system, obtained by the discrete “Verlet” algorithm commonly used in molecular dynamics simulations, fluctuates but is conserved in the mean. This is explained by the existence...

  16. Identification of dynamical hinge points of the L1 ligase molecular switch.

    Science.gov (United States)

    Giambasu, George M; Lee, Tai-Sung; Sosa, Carlos P; Robertson, Michael P; Scott, William G; York, Darrin M

    2010-04-01

    The L1 ligase is an in vitro selected ribozyme that uses a noncanonically base-paired ligation site to catalyze regioselectively and regiospecifically the 5' to 3' phosphodiester bond ligation, a reaction relevant to origin of life hypotheses that invoke an RNA world scenario. The L1 ligase crystal structure revealed two different conformational states that were proposed to represent the active and inactive forms. It remains an open question as to what degree these two conformers persist as stable conformational intermediates in solution, and along what pathway are they able to interconvert. To explore these questions, we have performed a series of molecular dynamics simulations in explicit solvent of the inactive-active conformational switch in L1 ligase. Four simulations were performed departing from both conformers in both the reactant and product states, in addition to a simulation where local unfolding in the active state was induced. From these simulations, along with crystallographic data, a set of four virtual torsion angles that span two evolutionarily conserved and restricted regions were identified as dynamical hinge points in the conformational switch transition. The ligation site visits three distinct states characterized by hydrogen bond patterns that are correlated with the formation of specific contacts that may promote catalysis. The insights gained from these simulations contribute to a more detailed understanding of the coupled catalytic/conformational switch mechanism of L1 ligase that may facilitate the design and engineering of new catalytic riboswitches.

  17. Machine Learning of Accurate Energy-Conserving Molecular Force Fields

    CERN Document Server

    Chmiela, Stefan; Sauceda, Huziel E; Poltavsky, Igor; Schütt, Kristof; Müller, Klaus-Robert

    2016-01-01

    Using conservation of energy -- a fundamental property of closed classical and quantum mechanical systems -- we develop an efficient gradient-domain machine learning (GDML) approach to construct accurate molecular force fields using a restricted number of samples from ab initio molecular dynamics (AIMD) trajectories. The GDML implementation is able to reproduce global potential-energy surfaces of intermediate-size molecules with an accuracy of 0.3 kcal/mol for energies and 1 kcal/mol/{\\AA} for atomic forces using only 1000 conformational geometries for training. We demonstrate this accuracy for AIMD trajectories of molecules, including benzene, toluene, naphthalene, ethanol, uracil, and aspirin. The challenge of constructing conservative force fields is accomplished in our work by learning in a Hilbert space of vector-valued functions that obey the law of energy conservation. The GDML approach enables quantitative molecular dynamics simulations for molecules at a fraction of cost of explicit AIMD calculations...

  18. Amino acid properties conserved in molecular evolution.

    Directory of Open Access Journals (Sweden)

    Witold R Rudnicki

    Full Text Available That amino acid properties are responsible for the way protein molecules evolve is natural and is also reasonably well supported both by the structure of the genetic code and, to a large extent, by the experimental measures of the amino acid similarity. Nevertheless, there remains a significant gap between observed similarity matrices and their reconstructions from amino acid properties. Therefore, we introduce a simple theoretical model of amino acid similarity matrices, which allows splitting the matrix into two parts - one that depends only on mutabilities of amino acids and another that depends on pairwise similarities between them. Then the new synthetic amino acid properties are derived from the pairwise similarities and used to reconstruct similarity matrices covering a wide range of information entropies. Our model allows us to explain up to 94% of the variability in the BLOSUM family of the amino acids similarity matrices in terms of amino acid properties. The new properties derived from amino acid similarity matrices correlate highly with properties known to be important for molecular evolution such as hydrophobicity, size, shape and charge of amino acids. This result closes the gap in our understanding of the influence of amino acids on evolution at the molecular level. The methods were applied to the single family of similarity matrices used often in general sequence homology searches, but it is general and can be used also for more specific matrices. The new synthetic properties can be used in analyzes of protein sequences in various biological applications.

  19. Electronic Transport Properties of a Naphthopyran-Based Optical Molecular Switch:an ab initio Study

    Institute of Scientific and Technical Information of China (English)

    XIA Cai-Juan; LIU De-Sheng; ZHANG Ying-Tang

    2011-01-01

    The electronic transport properties of a. Naphthopyran-based molecular optical switch are investigated by using the nonequilibrium Green's Function formalism combined with first-principles density functional theory. The molecule that comprises the switch can convert between its open and closed forms upon photoexcitation. Theoretical results show that the current through the open form is significantly larger than that through the closed form, which is different from other optical switches based on ring-opening reactions of the molecular bridge. The maximum on-off ratio (about 90) can be obtained at 1.4 V. The physical origin of the switching behavior is interpreted based on the spatial distributions of molecular orbitals and the HOMO-LUMO gap. Our result shows that the naphthopyran-based molecule is a good candidate for optical molecular switches and will be useful in the near future.%@@ ronic transport properties of a naphthopyran-based molecular optical switch are investigated by using the nonequilibrium Green's function formalism combined with first-principles density functional theory.The molecule that comprises the switch can convert between its open and closed forms upon photoexcitation.Theoretical results show that the current through the open form is significantly larger than that through the closed form,which is different from other optical switches based on ring-opening reactions of the molecular bridge.The maximum on-off ratio(about 90)can be obtained at 1.4 V.The physical origin of the switching behavior is interpreted based on the spatial distributions of molecular orbitals and the HOMO-LUMO gap.Our result shows that the naphthopyran-based molecule is a good candidate for optical molecular switches and will be useful in the near future.

  20. An Electrically Driven and Readable Molecular Monolayer Switch Based on a Solid Electrolyte.

    Science.gov (United States)

    Marchante, Elena; Crivillers, Núria; Buhl, Moritz; Veciana, Jaume; Mas-Torrent, Marta

    2016-01-01

    The potential application of molecular switches as active elements in information storage has been demonstrated through numerous works. Importantly, such switching capabilities have also been reported for self-assembled monolayers (SAMs). SAMs of electroactive molecules have recently been exploited as electrochemical switches. Typically, the state of these switches could be read out through their optical and/or magnetic response. These output reading processes are difficult to integrate into devices, and furthermore, there is a need to use liquid environments for switching the redox-active molecular systems. In this work, both of these challenges were overcome by using an ionic gel as the electrolyte medium, which led to an unprecedented solid-state device based on a single molecular layer. Moreover, electrochemical impedance has been successfully exploited as the output of the system.

  1. Light-Triggered Control of Plasmonic Refraction and Group Delay by Photochromic Molecular Switches

    DEFF Research Database (Denmark)

    Großmann, Malte; Klick, Alwin; Lemke, Christoph

    2015-01-01

    An interface supporting plasmonic switching is prepared from a gold substrate coated with a polymerfilm doped with photochromic molecular switches. A reversible light-induced change in the surface plasmon polariton dispersion curve of the interface is experimentally demonstrated, evidencing rever...... complex functionalities based on surface plasmon refraction and group delay....

  2. Switching at the nanoscale: chiroptical molecular switches and motors. : Section Title: Optical, Electron, and Mass Spectroscopy and Other Related Properties

    NARCIS (Netherlands)

    Browne, Wesley R.; Pijper, Dirk; Pollard, Michael M.; Feringa, Bernard; Amabilino, David B.

    2009-01-01

    A review on the recent developments in the field of chiroptical switches and nanomotors. Topics discussed include switching of mol. state, azobenzene-based chiroptical photoswitching, electrochiroptical switching, diarylethene-based chiroptical switches, mol. switching with circularly polarized

  3. Asymmetric stochastic switching driven by intrinsic molecular noise.

    Directory of Open Access Journals (Sweden)

    David Frigola

    Full Text Available Low-copy-number molecules are involved in many functions in cells. The intrinsic fluctuations of these numbers can enable stochastic switching between multiple steady states, inducing phenotypic variability. Herein we present a theoretical and computational study based on Master Equations and Fokker-Planck and Langevin descriptions of stochastic switching for a genetic circuit of autoactivation. We show that in this circuit the intrinsic fluctuations arising from low-copy numbers, which are inherently state-dependent, drive asymmetric switching. These theoretical results are consistent with experimental data that have been reported for the bistable system of the gallactose signaling network in yeast. Our study unravels that intrinsic fluctuations, while not required to describe bistability, are fundamental to understand stochastic switching and the dynamical relative stability of multiple states.

  4. Non-conservation of excitons in finite molecular chain

    Energy Technology Data Exchange (ETDEWEB)

    Tosic, Bratislav, E-mail: btosic@yahoo.co [Vojvodina Academy of Science and Arts, 21000 Novi Sad, Dunavska 37 (Serbia); Sajfert, Vjekoslav, E-mail: sajfertv@nadlanu.co [University of Novi Sad, Technical Faculty ' M. Pupin' , 23000 Zrenjanin, Djure Djakovica bb (Serbia); Maskovic, Ljiljana, E-mail: maskovicm@yahoo.co.u [Academy of Criminalistic and Police Studies, 11000 Belgrade, Zemun (Serbia); Bednar, Nikola, E-mail: bednar.nikola@gmail.co [University of Novi Sad, Faculty of Technical Sciences, 21000 Novi Sad, Trg Dositeja Obradovica 6 (Serbia)

    2010-11-15

    We have analyzed a linear molecular chain with exciton excitations when the number of excitons is not conserved. The dispersion law depends on two independent variables and it is surfaced in a 3D plot. The same conclusion is valid for the concentrations of excitons and exciton pairs. As it was expected, physical characteristics of the finite chain depend on spatial coordinates. All results are compared to the corresponding results of an infinite chain.

  5. Machine learning of accurate energy-conserving molecular force fields

    Science.gov (United States)

    Chmiela, Stefan; Tkatchenko, Alexandre; Sauceda, Huziel E.; Poltavsky, Igor; Schütt, Kristof T.; Müller, Klaus-Robert

    2017-01-01

    Using conservation of energy—a fundamental property of closed classical and quantum mechanical systems—we develop an efficient gradient-domain machine learning (GDML) approach to construct accurate molecular force fields using a restricted number of samples from ab initio molecular dynamics (AIMD) trajectories. The GDML implementation is able to reproduce global potential energy surfaces of intermediate-sized molecules with an accuracy of 0.3 kcal mol−1 for energies and 1 kcal mol−1 Å̊−1 for atomic forces using only 1000 conformational geometries for training. We demonstrate this accuracy for AIMD trajectories of molecules, including benzene, toluene, naphthalene, ethanol, uracil, and aspirin. The challenge of constructing conservative force fields is accomplished in our work by learning in a Hilbert space of vector-valued functions that obey the law of energy conservation. The GDML approach enables quantitative molecular dynamics simulations for molecules at a fraction of cost of explicit AIMD calculations, thereby allowing the construction of efficient force fields with the accuracy and transferability of high-level ab initio methods. PMID:28508076

  6. Molecular modeling and molecular dynamics simulation of the polarization switching phenomena in the ferroelectric polymers PVDF at the nanoscale

    Energy Technology Data Exchange (ETDEWEB)

    Bystrov, V.S., E-mail: bystrov@ua.pt [Department of Materials and Ceramic Engineering and CICECO, University of Aveiro, 3810-193 Aveiro (Portugal); Institute of Mathematical Problems of Biology RAS, 142290, Pushchino (Russian Federation)

    2014-01-01

    The molecular modeling and molecular dynamics of polarization switching for the ferroelectric films model of polyvinylidene fluoride (PVDF) are investigated at the nanoscale. We consider a molecular model of PVDF film, consisting of two and four a chains [–CH2–CF2–]{sub n} limited by n=6 elementary units. The first-principle approach is applied to the switching and kinetics of these models. Two types of behavior were established for PVDF chains: simultaneous and sequential rotation in high and low electric fields. Kinetics of sequential polarization switching shows a homogeneous critical behavior in the low electric field with a critical point at Landau–Ginzburg–Devonshire (LGD) coercive field E=E{sub C}. This type of kinetics demonstrates a kink-like behavior for polarization solitary wave propagation. The simultaneous type of kinetics demonstrates the total domain-like polarization switching, corresponding to exponential behavior of switching time in high electric field as for bulk samples. Corresponding LGD intrinsic coercive field for a two-chain and four-chains model is E{sub C}∼2.0 GV/m with revealing size effect. Obtained results show common quantum nature of PVDF chains switching phenomena—the quantum interaction of the PVDF molecular orbitals under applied electric field at the nanoscale level. The results obtained are compared with experimental data.

  7. The stochastic behavior of a molecular switching circuit with feedback

    Directory of Open Access Journals (Sweden)

    Smith Eric

    2007-05-01

    Full Text Available Abstract Background Using a statistical physics approach, we study the stochastic switching behavior of a model circuit of multisite phosphorylation and dephosphorylation with feedback. The circuit consists of a kinase and phosphatase acting on multiple sites of a substrate that, contingent on its modification state, catalyzes its own phosphorylation and, in a symmetric scenario, dephosphorylation. The symmetric case is viewed as a cartoon of conflicting feedback that could result from antagonistic pathways impinging on the state of a shared component. Results Multisite phosphorylation is sufficient for bistable behavior under feedback even when catalysis is linear in substrate concentration, which is the case we consider. We compute the phase diagram, fluctuation spectrum and large-deviation properties related to switch memory within a statistical mechanics framework. Bistability occurs as either a first-order or second-order non-equilibrium phase transition, depending on the network symmetries and the ratio of phosphatase to kinase numbers. In the second-order case, the circuit never leaves the bistable regime upon increasing the number of substrate molecules at constant kinase to phosphatase ratio. Conclusion The number of substrate molecules is a key parameter controlling both the onset of the bistable regime, fluctuation intensity, and the residence time in a switched state. The relevance of the concept of memory depends on the degree of switch symmetry, as memory presupposes information to be remembered, which is highest for equal residence times in the switched states. Reviewers This article was reviewed by Artem Novozhilov (nominated by Eugene Koonin, Sergei Maslov, and Ned Wingreen.

  8. A predictive model of intein insertion site for use in the engineering of molecular switches.

    Directory of Open Access Journals (Sweden)

    James Apgar

    Full Text Available Inteins are intervening protein domains with self-splicing ability that can be used as molecular switches to control activity of their host protein. Successfully engineering an intein into a host protein requires identifying an insertion site that permits intein insertion and splicing while allowing for proper folding of the mature protein post-splicing. By analyzing sequence and structure based properties of native intein insertion sites we have identified four features that showed significant correlation with the location of the intein insertion sites, and therefore may be useful in predicting insertion sites in other proteins that provide native-like intein function. Three of these properties, the distance to the active site and dimer interface site, the SVM score of the splice site cassette, and the sequence conservation of the site showed statistically significant correlation and strong predictive power, with area under the curve (AUC values of 0.79, 0.76, and 0.73 respectively, while the distance to secondary structure/loop junction showed significance but with less predictive power (AUC of 0.54. In a case study of 20 insertion sites in the XynB xylanase, two features of native insertion sites showed correlation with the splice sites and demonstrated predictive value in selecting non-native splice sites. Structural modeling of intein insertions at two sites highlighted the role that the insertion site location could play on the ability of the intein to modulate activity of the host protein. These findings can be used to enrich the selection of insertion sites capable of supporting intein splicing and hosting an intein switch.

  9. Electrically controllable molecular spin crossover switching in Fe(phen)2 (NCS)2 thin film

    Science.gov (United States)

    Mondal, Chaitali; Mandal, Swapan K.

    2016-10-01

    Spin crossover molecular complex Fe(phen)2(NCS)2 in thin film form (20-300 nm) is obtained by simple dip-coating technique on glass substrates. The growth of the molecular films is confirmed by optical and X-ray diffraction data. The morphology of the samples shows distributed nanocrystals with an average size ca. 12 nm. We measure the current (I)-voltage (V) characteristics of a device with 300 nm film thickness and show that application of electric field can induce spin state switching. The electric field experienced by individual nanocrystals separated by nanometric gap is supposed to be quite high and is plausibly playing the crucial role in instigating switching in molecular nanocrystals. The result is quite significant towards developing room temperature molecular spin cross-over switching devices in the nanoscale limit.

  10. Correlated rotational switching in two-dimensional self-assembled molecular rotor arrays

    Science.gov (United States)

    Wasio, Natalie A.; Slough, Diana P.; Smith, Zachary C.; Ivimey, Christopher J.; Thomas, Samuel W., III; Lin, Yu-Shan; Sykes, E. Charles H.

    2017-07-01

    Molecular devices are capable of performing a number of functions from mechanical motion to simple computation. Their utility is somewhat limited, however, by difficulties associated with coupling them with either each other or with interfaces such as electrodes. Self-assembly of coupled molecular devices provides an option for the construction of larger entities that can more easily integrate with existing technologies. Here we demonstrate that ordered organometallic arrays can be formed spontaneously by reaction of precursor molecular rotor molecules with a metal surface. Scanning tunnelling microscopy enables individual rotors in the arrays to be switched and the resultant switches in neighbouring rotors imaged. The structure and dimensions of the ordered molecular rotor arrays dictate the correlated switching properties of the internal submolecular rotor units. Our results indicate that self-assembly of two-dimensional rotor crystals produces systems with correlated dynamics that would not have been predicted a priori.

  11. Energy conservation in molecular dynamics simulations of classical systems.

    Science.gov (United States)

    Toxvaerd, Søren; Heilmann, Ole J; Dyre, Jeppe C

    2012-06-14

    Classical Newtonian dynamics is analytic and the energy of an isolated system is conserved. The energy of such a system, obtained by the discrete "Verlet" algorithm commonly used in molecular dynamics simulations, fluctuates but is conserved in the mean. This is explained by the existence of a "shadow Hamiltonian" H [S. Toxvaerd, Phys. Rev. E 50, 2271 (1994)], i.e., a Hamiltonian close to the original H with the property that the discrete positions of the Verlet algorithm for H lie on the analytic trajectories of H. The shadow Hamiltonian can be obtained from H by an asymptotic expansion in the time step length. Here we use the first non-trivial term in this expansion to obtain an improved estimate of the discrete values of the energy. The investigation is performed for a representative system with Lennard-Jones pair interactions. The simulations show that inclusion of this term reduces the standard deviation of the energy fluctuations by a factor of 100 for typical values of the time step length. Simulations further show that the energy is conserved for at least one hundred million time steps provided the potential and its first four derivatives are continuous at the cutoff. Finally, we show analytically as well as numerically that energy conservation is not sensitive to round-off errors.

  12. N-dimensional switch function for energy conservation in multiprocess reaction dynamics.

    Science.gov (United States)

    Mogo, César; Brandão, João

    2016-06-15

    The MReaDy program was designed for studying Multiprocess Reactive Dynamic systems, that is, complex chemical systems involving different and concurrent reactions. It builds a global potential energy surface integrating a variety of potential energy surfaces, each one of them representing an elementary reaction expected to play a role in the chemical process. For each elementary reaction, energy continuity problems may happen in the transition between potential energy surfaces due to differences in the functional form for each of the fragments, especially if built by different authors. A N-dimensional switch function is introduced in MReaDy in order to overcome such a problem. As an example, results of a collision trajectory calculation for H2  + OH → H3 O are presented, showing smooth transition in the potential energy, leading to conservation in the total energy. Calculations for a hydrogen combustion system from 1000 K up to 4000 K shows a variation of 0.012% when compared to the total energy of the system. © 2016 Wiley Periodicals, Inc.

  13. Light-induced photoisomerization of a diarylethene molecular switch on solid surfaces

    Science.gov (United States)

    Nickel, Fabian; Bernien, Matthias; Herder, Martin; Wrzalek, Sandro; Chittas, Pantelis; Kraffert, Kai; Arruda, Lucas M.; Kipgen, Lalminthang; Krüger, Dennis; Hecht, Stefan; Kuch, Wolfgang

    2017-09-01

    Diarylethenes are molecular switches, the state of which can efficiently be controlled by illumination with ultraviolet or visible light. To use the change in the molecular properties when switching between the two states for a specific function, direct contact with solid surfaces is advantageous as it provides immobilization. Here we present a study of a diarylethene derivate (T-DAE, 1,2-bis(5-methyl-2-phenylthiazol-4-yl)cyclopent-1-ene) in direct contact with highly ordered graphite as well as with semimetallic Bi(1 1 1) surfaces by x-ray photoelectron spectroscopy, x-ray absorption spectroscopy and simulated spectra based on density functional theory. On both surfaces, the molecule can be switched from its open to its closed form by 325-475 nm broadband or ultraviolet illumination. On the other hand, back isomerization to the ring-open T-DAE was not possible.

  14. The Development and Study of Molecular Electronic Switches and their Field-Effect Transistor (FET) Device Properties

    Science.gov (United States)

    2015-02-27

    reviewed journals: Final Report: The Development and Study of Molecular Electronic Switches and their Field -Effect Transistor (FET) Device Properties...fabrication of nanostructures can serve as building blocks for molecular switching devices, organic light-emitting diodes (OLEDs), photovoltaic, field ...arrays, and photovoltaic cells. We are currently synthesizing the iodo-substituted perylene diimide (6) that will be cross -coupled to the above switch

  15. Cyclic conductance switching in networks of redox-active molecular junctions.

    Science.gov (United States)

    Liao, Jianhui; Agustsson, Jon S; Wu, Songmei; Schönenberger, Christian; Calame, Michel; Leroux, Yann; Mayor, Marcel; Jeannin, Olivier; Ran, Ying-Fen; Liu, Shi-Xia; Decurtins, Silvio

    2010-03-10

    Redox-active dithiolated tetrathiafulvalene derivatives (TTFdT) were inserted in two-dimensional nanoparticle arrays to build interlinked networks of molecular junctions. Upon oxidation of the TTFdT to the dication state, we observed a conductance increase of the networks by up to 1 order of magnitude. Successive oxidation and reduction cycles demonstrated a clear switching behavior of the molecular junction conductance. These results show the potential of interlinked nanoparticle arrays as chemical sensors.

  16. Conserved Molecular Mechanisms Underlying Homeostasis of the Golgi Complex

    Directory of Open Access Journals (Sweden)

    Cathal Wilson

    2010-01-01

    Full Text Available The Golgi complex performs a central function in the secretory pathway in the sorting and sequential processing of a large number of proteins destined for other endomembrane organelles, the plasma membrane, or secretion from the cell, in addition to lipid metabolism and signaling. The Golgi apparatus can be regarded as a self-organizing system that maintains a relatively stable morphofunctional organization in the face of an enormous flux of lipids and proteins. A large number of the molecular players that operate in these processes have been identified, their functions and interactions defined, but there is still debate about many aspects that regulate protein trafficking and, in particular, the maintenance of these highly dynamic structures and processes. Here, we consider how an evolutionarily conserved underlying mechanism based on retrograde trafficking that uses lipids, COPI, SNAREs, and tethers could maintain such a homeodynamic system.

  17. Thiacalix[4]arene based reconfigurable molecular switches: set-reset memorized sequential device.

    Science.gov (United States)

    Kumar, Manoj; Kumar, Rajesh; Bhalla, Vandana

    2011-12-21

    The fluorescent chemosensors 3, 5 and 7 based on thiacalix[4]arene bearing naphthyl groups have been designed and synthesized. The optical chemosensor 3 based on a thiacalix[4]arene of cone conformation behaves as "turn-on" optical chemosensor for Fe(3+) and F(-) ions. However, chemosensors 5 and 7 based on a thiacalix[4]arene of 1,3-alternate conformation demonstrate "turn-on" optical behaviour for Hg(2+), F(-) ions (with receptor 5 as turn-on for K(+) ions also) and "turn-off" behaviour for Fe(3+) ions. The simultaneous presence of Fe(3+) and Hg(2+) or K(+) or F(-) ions results in formulation of reversible "on-off" switches. Various molecular logic gates developed in response to molecular switching between these chemical inputs have been integrated into sequential logic circuits with memory function in a feedback loop which mimics "set-reset" molecular level information processing device.

  18. Sox2 transcription network acts as a molecular switch to regulate properties of neural stem cells

    Institute of Scientific and Technical Information of China (English)

    Koji; Shimozaki

    2014-01-01

    Neural stem cells(NSCs) contribute to ontogeny by producing neurons at the appropriate time and location. Neurogenesis from NSCs is also involved in various biological functions in adults. Thus, NSCs continue to exert their effects throughout the lifespan of the organism. The mechanism regulating the core functional properties of NSCs is governed by intra- and extracellular signals. Among the transcription factors that serve as molecular switches, Sox2 is considered a key factor in NSCs. Sox2 forms a core network with partner factors, thereby functioning as a molecular switch. This review discusses how the network of Sox2 partner and target genes illustrates the molecular characteristics of the mechanism underlying the self-renewal and multipotency of NSCs.

  19. Investigation of a metal-organic interface. Realization and understanding of a molecular switch

    Energy Technology Data Exchange (ETDEWEB)

    Neucheva, Olga [Forschungszentrum Juelich (DE). Institute of Bio- and Nanosystems (IBN), Functional Nanostructures at Surfaces (IBN-3)

    2010-07-01

    The field of molecular organic electronics is an emerging and very dynamic area. The continued trend to miniaturisation, combined with increasing complexity and cost of production in conventional semiconductor electronics, forces companies to turn their attention to alternatives that promise the next levels of scale at significantly lower cost. After consumer electronic devices based on organic transistors, such as TVs and book readers, have already been presented, molecular electronics is expected to offer the next breakthrough in feature size. Unfortunately, most of the organic/metal interfaces contain intrinsic defects that break the homogeneity of the interface properties. In this thesis, the electronic and structural properties of such defects were examined in order to understand the influence of the inhomogeneities on the quality of the interface layer. However, the main focus of this work was the investigation of the local properties of a single molecule. Taking advantage of the Scanning Tunnelling Microscope's (STM's) ability to act as a local probe, a single molecular switch was realized and studied. Moreover, in close collaboration with theory groups, the underlying mechanism driving the switching process was identified and described. Besides the investigation of the switching process, the ability of the STM to build nanostructures of different shapes from large organic molecules was shown. Knowing the parameters for realization and control of the switching process and for building the molecular corrals, the results of this investigation enable the reconstruction of the studied molecular ensemble and its deployment in electric molecular circuits, constituting a next step towards further miniaturization of electronic devices. (orig.)

  20. A pH-sensitive peptide-containing lasso molecular switch.

    Science.gov (United States)

    Clavel, Caroline; Fournel-Marotte, Karine; Coutrot, Frédéric

    2013-09-17

    The synthesis of a peptide-containing lasso molecular switch by a self-entanglement strategy is described. The interlocked rotaxane molecular machine consists of a benzometaphenylene[25]crown-8 (BMP25C8) macrocycle surrounding a molecular axle. This molecular axle contains a tripeptidic sequence and two molecular stations: a N-benzyltriazolium and a pH-sensitive anilinium station. The tripeptide is located between the macrocycle and the triazolium station, so that its conformation can be tailored depending on the shuttling of the macrocycle from one station to the other. At acidic pH, the macrocycle resides around the anilinium moiety, whereas it shuttles around the triazolium station after deprotonation. This molecular machinery thus forces the lasso to adopt a tightened or a loosened conformation.

  1. The importance of the rotor in hydrazone-based molecular switches

    Directory of Open Access Journals (Sweden)

    Xin Su

    2012-06-01

    Full Text Available The pH-activated E/Z isomerization of a series of hydrazone-based systems having different functional groups as part of the rotor (R = COMe, CN, Me, H, was studied. The switching efficiency of these systems was compared to that of a hydrazone-based molecular switch (R = COOEt whose E/Z isomerization is fully reversible. It was found that the nature of the R group is critical for efficient switching to occur; the R group should be a moderate H-bond acceptor in order to (i provide enough driving force for the rotor to move upon protonation, and (ii stabilize the obtained Z configuration, to achieve full conversion.

  2. Ab initio theory for current-induced molecular switching: Melamine on Cu(001)

    KAUST Repository

    Ohto, Tatsuhiko

    2013-05-28

    Melamine on Cu(001) is mechanically unstable under the current of a scanning tunneling microscope tip and can switch among configurations. However, these are not equally accessible, and the switching critical current depends on the bias polarity. In order to explain such rich phenomenology, we have developed a scheme to evaluate the evolution of the reaction paths and activation barriers as a function of bias, which is rooted in the nonequilibrium Green\\'s function method implemented within density functional theory. This, combined with the calculation of the inelastic electron tunneling spectroscopy signal, allows us to identify the vibrational modes promoting the observed molecular conformational changes. Finally, once our ab initio results are used within a resonance model, we are able to explain the details of the switching behavior, such as its dependence on the bias polarity, and the noninteger power relation between the reaction rate constants and both the bias voltage and the electric current. © 2013 American Physical Society.

  3. Electronic Transport Properties of an Anthraquinone-Based Molecular Switch with Carbon Nanotube Electrodes

    Institute of Scientific and Technical Information of China (English)

    ZHAO Peng; LIU De-Sheng

    2012-01-01

    Based on the nonequilibrium Green's function method and density functional theory calculations,we theoretically investigate the electronic transport properties of an anthraquinone-based molecular switch with carbon nanotube electrodes.The molecules that comprise the switch can convert between reduced hydroquinone (HQ) and oxidized anthraquinne (AQ) states via redox reactions.Our results show that the on-off ratio is increased one order of magnitude when compared to the case of gold electrodes.Moreover,an obvious negative differential resistance behavior at much low bias (0.07 V) is observed in the HQ form.%Based on the nonequilihrium Green's function method and density functional theory calculations, we theoretically investigate the electronic transport properties of an anthraquinone-based molecular switch with carbon nanotube electrodes. The molecules that comprise the switch can convert between reduced hydroquinone (HQ) and oxidized anthraquinne (AQ) states via redox reactions. Our results show that the on-off ratio is increased one order of magnitude when compared to the case of gold electrodes. Moreover, an obvious negative differential resistance behavior at much low bias (0.07 V) is observed in the HQ form.

  4. The theoretical investigation of one of the derivatives of 1, 2-dithienylcyclopentene as a molecular switch.

    Science.gov (United States)

    Safarpour, Mohammad Ali; Hashemianzadeh, Seyed Majid; Kasaeian, Azam

    2008-04-01

    The structural and electronic properties of a three-state molecular switch-an active device in a nano-electronic circuit-were studied using the B3LYP/6-31G* method. Due to its chemical stability, high conductivity upon doping, and non-linear optical properties, polythiophene is among the most widely studied conjugated organic polymers, both experimentally and theoretically. The aim of the present work was to theoretically study a very complex case: a three-state switch synthesized and experimentally investigated by Nishida et al. (Org Lett 6:2523-2526, 2004). An initial set of test calculations showed B3LYP level of theory and 6-31G* basis set to be the most appropriate for our purpose, i.e., the study of the structure, charge and spin distributions, as well as electrical characteristics such as electric polarizability, HOMO-LUMO gap (HLG) and electric dipole moment, for one of the 1,2-dithienylcyclopentene derivatives. Also, natural bond orbital analyses were performed to calculate local charges and charge transfers in order to study the capability of the molecule as a molecular switch. The results reported here are of general significance, and demonstrate that it is possible to use certain structural and electrical properties to understand and design electro-photochromic compounds showing a switching function in cases where stable forms can be exchanged by light or electron transfer. Figure Model of a thiophene wire incorporating a redox active unit.

  5. Breast Conservation Therapy: The Influence of Molecular Subtype and Margins

    Energy Technology Data Exchange (ETDEWEB)

    Demirci, Senem, E-mail: senem.demirci@ege.edu.tr [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Department of Radiation Oncology, Ege University Faculty of Medicine, Izmir (Turkey); Broadwater, Gloria [Department of Biostatistics and Bioinformatics, Duke Cancer Institute, Durham, NC (United States); Cancer and Leukemia Group B Statistical Center, Duke Cancer Institute, Durham, NC (United States); Marks, Lawrence B. [Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, NC (United States); Clough, Robert; Prosnitz, Leonard R. [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States)

    2012-07-01

    Purpose: To evaluate treatment results and prognostic factors, especially margin status and molecular subtype, in early-stage breast cancer patients treated with breast conservation therapy (BCT). Methods and Materials: The records of 1,058 Stage I or II breast cancer patients treated with BCT (surgical excision plus radiotherapy) at Duke University Medical Center, Durham, North Carolina, from 1985-2005 were retrospectively reviewed. Conventional receptor analyses were used as surrogate markers for molecular subtype classification (luminal A, luminal B, Her2 positive, and basal like). Actuarial estimates of overall survival (OS), cause-specific survival (CSS), failure-free survival, and locoregional control (LRC) were computed by use of Kaplan-Meier plots. We analyzed prognostic variables for significance using Cox proportional hazards univariate and multivariate analysis. The study was approved by the Duke University Medical Center Institutional Review Board. Results: The median age of the patients was 56 years (range, 18-89 years). Of the patients, 80% had T1 disease and 66% N0 disease pathologically. With a median follow-up of 9.8 years, an in-breast recurrence developed in 53 patients and 10 patients had nodal failure. For all patients, the 10-year CSS rate was 94%; LRC rate, 94%; and failure-free survival rate, 88%. Luminal A patients had a CSS rate of 95% and LRC rate of 99%. Basal-type patients appeared to do worse, with regard to both CSS rate (74%) and LRC rate (76%), but the numbers were small and the difference was not statistically significant. LRC rates of patients with negative margins (widely negative, close, and extent of margin not known) were virtually identical (93%, 96%, and 94%, respectively). Those with positive margins appeared to fare slightly worse based on LRC rate (88%), but again, the numbers were small and the difference was not statistically significant. Conclusions: BCT remains the treatment of choice for early-stage breast cancer

  6. Transport dynamics of molecular motors that switch between an active and inactive state.

    Science.gov (United States)

    Pinkoviezky, I; Gov, N S

    2013-08-01

    Molecular motors are involved in key transport processes in the cell. Many of these motors can switch from an active to a nonactive state, either spontaneously or depending on their interaction with other molecules. When active, the motors move processively along the filaments, while when inactive they are stationary. We treat here the simple case of spontaneously switching motors, between the active and inactive states, along an open linear track. We use our recent analogy with vehicular traffic, where we go beyond the mean-field description. We map the phase diagram of this system, and find that it clearly breaks the symmetry between the different phases, as compared to the standard total asymmetric exclusion process. We make several predictions that may be testable using molecular motors in vitro and in living cells.

  7. Research Update: Molecular electronics: The single-molecule switch and transistor

    Directory of Open Access Journals (Sweden)

    Kai Sotthewes

    2014-01-01

    Full Text Available In order to design and realize single-molecule devices it is essential to have a good understanding of the properties of an individual molecule. For electronic applications, the most important property of a molecule is its conductance. Here we show how a single octanethiol molecule can be connected to macroscopic leads and how the transport properties of the molecule can be measured. Based on this knowledge we have realized two single-molecule devices: a molecular switch and a molecular transistor. The switch can be opened and closed at will by carefully adjusting the separation between the electrical contacts and the voltage drop across the contacts. This single-molecular switch operates in a broad temperature range from cryogenic temperatures all the way up to room temperature. Via mechanical gating, i.e., compressing or stretching of the octanethiol molecule, by varying the contact's interspace, we are able to systematically adjust the conductance of the electrode-octanethiol-electrode junction. This two-terminal single-molecule transistor is very robust, but the amplification factor is rather limited.

  8. Some fundamental problems for an energy conserving adaptive resolution molecular dynamics scheme

    OpenAIRE

    Site, L. Delle

    2007-01-01

    Adaptive resolution molecular dynamics (MD) schemes allow for changing the number of degrees of freedom on the fly and preserve the free exchange of particles between regions of different resolution. There are two main alternatives on how to design the algorithm to switch resolution using auxiliary ''switching'' functions; force based and potential energy based approach. In this work we show that, in the framework of classical MD, the latter presents fundamental conceptual problems which make...

  9. Molecular dynamics algorithm enforcing energy conservation for microcanonical simulations.

    Science.gov (United States)

    Salueña, Clara; Avalos, Josep Bonet

    2014-05-01

    A reversible algorithm [enforced energy conservation (EEC)] that enforces total energy conservation for microcanonical simulations is presented. The key point is the introduction of the discrete-gradient method to define the forces from the conservative potentials, instead of the direct use of the force field at the actual position of the particle. We have studied the performance and accuracy of the EEC in two cases, namely Lennard-Jones fluid and a simple electrolyte model. Truncated potentials that usually induce inaccuracies in energy conservation are used. In particular, the reaction field approach is used in the latter. The EEC is able to preserve energy conservation for a long time, and, in addition, it performs better than the Verlet algorithm for these kinds of simulations.

  10. Molecular switches under TGFβ signalling during progression from cardiac hypertrophy to heart failure.

    Science.gov (United States)

    Heger, J; Schulz, R; Euler, G

    2016-01-01

    Cardiac hypertrophy is a mechanism to compensate for increased cardiac work load, that is, after myocardial infarction or upon pressure overload. However, in the long run cardiac hypertrophy is a prevailing risk factor for the development of heart failure. During pathological remodelling processes leading to heart failure, decompensated hypertrophy, death of cardiomyocytes by apoptosis or necroptosis and fibrosis as well as a progressive dysfunction of cardiomyocytes are apparent. Interestingly, the induction of hypertrophy, cell death or fibrosis is mediated by similar signalling pathways. Therefore, tiny changes in the signalling cascade are able to switch physiological cardiac remodelling to the development of heart failure. In the present review, we will describe examples of these molecular switches that change compensated hypertrophy to the development of heart failure and will focus on the importance of the signalling cascades of the TGFβ superfamily in this process. In this context, potential therapeutic targets for pharmacological interventions that could attenuate the progression of heart failure will be discussed.

  11. Electrochemical control of quantum interference in anthraquinone-based molecular switches

    DEFF Research Database (Denmark)

    Markussen, Troels; Schiøtz, Jakob; Thygesen, Kristian Sommer

    2010-01-01

    Using first-principles calculations we analyze the electronic transport properties of a recently proposed anthraquinone-based electrochemical switch. Robust conductance on/off ratios of several orders of magnitude are observed due to destructive quantum interference present in the anthraquinone b...... of hopping via the localized orbitals. The topology of the tight-binding model, which is dictated by the symmetries of the molecular orbitals, determines the amount of quantum interference.......Using first-principles calculations we analyze the electronic transport properties of a recently proposed anthraquinone-based electrochemical switch. Robust conductance on/off ratios of several orders of magnitude are observed due to destructive quantum interference present in the anthraquinone...

  12. Transient photocurrent in molecular junctions: singlet switching on and triplet blocking.

    Science.gov (United States)

    Petrov, E G; Leonov, V O; Snitsarev, V

    2013-05-14

    The kinetic approach adapted to describe charge transmission in molecular junctions, is used for the analysis of the photocurrent under conditions of moderate light intensity of the photochromic molecule. In the framework of the HOMO-LUMO model for the single electron molecular states, the analytic expressions describing the temporary behavior of the transient and steady state sequential (hopping) as well as direct (tunnel) current components have been derived. The conditions at which the current components achieve their maximal values are indicated. It is shown that if the rates of charge transmission in the unbiased molecular diode are much lower than the intramolecular singlet-singlet excitation/de-excitation rate, and the threefold degenerated triplet excited state of the molecule behaves like a trap blocking the charge transmission, a possibility of a large peak-like transient switch-on photocurrent arises.

  13. A reversible DNA-silver nanoclusters-based molecular fluorescence switch and its use for logic gate operation.

    Science.gov (United States)

    Huang, Zhenzhen; Ren, Jinsong; Qu, Xiaogang

    2012-03-01

    Molecule-like silver nanoclusters (AgNCs) with few to tens of atoms are highly sensitive to the sequence and structure of DNA stabilizers. In this paper, a novel pH-triggered reversible molecular fluorescence switch is developed by taking advantage of the DNA-dependent fluorescence pH response of AgNCs. The DNA-AgNCs fluorescence switch simultaneously addresses concerns of simple construction strategy, efficient design and organic-solvent-free operation. Moreover, the excellent photostability and biocompatibility of AgNCs provide great potential for application of the DNA-AgNCs fluorescence switch in the development of functional molecular devices. Specifically, we apply the DNA-AgNCs fluorescence switch combined with the DNA sequence-dependent pH response pattern of AgNCs for construction of molecular logic gates.

  14. [The application of DNA molecular markers in conservation of the rare and endangered medicinal plants].

    Science.gov (United States)

    Yan, Zhi-Feng; Zhang, Ben-Gang; Zhang, Zhao; Xia, Tian-Rui

    2005-12-01

    In this paper, the advance in DNA molecular markers techniques in recent years was reviewed. The application of DNA markers in conservation of the rare and endangered medicinal plants was explicated, of which included identification of germ-plasm resource, determination of the habitats unite which should be protected in situ, sampling strategies of ex-situ conservation, evaluation of the conservation effects of the rare and endangered medicinal plants, as well as elucidation of their endangered mechanism etc. The information could help drawing up conservation strategies and conservation measures for references.

  15. All-optical integrated logic operations based on chemical communication between molecular switches.

    Science.gov (United States)

    Silvi, Serena; Constable, Edwin C; Housecroft, Catherine E; Beves, Jonathon E; Dunphy, Emma L; Tomasulo, Massimiliano; Raymo, Françisco M; Credi, Alberto

    2009-01-01

    Molecular logic gates process physical or chemical "inputs" to generate "outputs" based on a set of logical operators. We report the design and operation of a chemical ensemble in solution that behaves as integrated AND, OR, and XNOR gates with optical input and output signals. The ensemble is composed of a reversible merocyanine-type photoacid and a ruthenium polypyridine complex that functions as a pH-controlled three-state luminescent switch. The light-triggered release of protons from the photoacid is used to control the state of the transition-metal complex. Therefore, the two molecular switching devices communicate with one another through the exchange of ionic signals. By means of such a double (optical-chemical-optical) signal-transduction mechanism, inputs of violet light modulate a luminescence output in the red/far-red region of the visible spectrum. Nondestructive reading is guaranteed because the green light used for excitation in the photoluminescence experiments does not affect the state of the gate. The reset is thermally driven and, thus, does not involve the addition of chemicals and accumulation of byproducts. Owing to its reversibility and stability, this molecular device can afford many cycles of digital operation.

  16. Photo-driven molecular switch based on the photochromism and solvatochromism of diarylethene dialdehyde

    Institute of Scientific and Technical Information of China (English)

    BIN YueJing; ZHAO FuQun; CHEN ZiHui; ZHANG FuShi

    2008-01-01

    The two distinct characters of diarylethene dialdehyde derivative-photochromism and solvatochrom-ism are displayed in particular circumstances. The fluorescence of phosphorus (Ⅲ) tetrabenzotri-azacorrole can be reversibly regulated by the three kinds of status of the diarylethene dialdehyde, col-orless ring-opened form, red ring-closed form, and blue ring-closed form, which is gated by visible light, ultraviolet light and ethanol individually or jointly. Based on this effect, a novel molecular INH logic switch is proposed.

  17. Bacterial chromosome segregation: structure and DNA binding of the Soj dimer — a conserved biological switch

    OpenAIRE

    Leonard, Thomas A.; Butler, P Jonathan; Löwe, Jan

    2005-01-01

    Soj and Spo0J of the Gram-negative hyperthermophile Thermus thermophilus belong to the conserved ParAB family of bacterial proteins implicated in plasmid and chromosome partitioning. Spo0J binds to DNA near the replication origin and localises at the poles following initiation of replication. Soj oscillates in the nucleoid region in an ATP- and Spo0J-dependent fashion. Here, we show that Soj undergoes ATP-dependent dimerisation in solution and forms nucleoprotein filaments with DNA. Crystal s...

  18. A molecular beacon-based DNA switch for reversible pH sensing in vesicles and live cells.

    Science.gov (United States)

    Narayanaswamy, Nagarjun; Nair, Raji R; Suseela, Y V; Saini, Deepak Kumar; Govindaraju, T

    2016-07-01

    In this Communication, a molecular beacon-based DNA switch (LMB) is developed as an efficient and reversible pH sensing probe. Remarkably, LMB exhibited reversible structural transition between the closed (molecular beacon) and open (A-motif) states very efficiently in synthetic vesicles and live cells without the need for any transfection agents.

  19. A pH-sensitive lasso-based rotaxane molecular switch.

    Science.gov (United States)

    Clavel, Caroline; Romuald, Camille; Brabet, Emile; Coutrot, Frédéric

    2013-02-25

    The synthesis of a pH-sensitive two-station [1]rotaxane molecular switch by self-entanglement of a non-interlocked hermaphrodite molecule, containing an anilinium and triazole moieties, is reported. The anilinium was chosen as the best template for the macrocycle benzometaphenylene[25]crown-8 (BMP25C8) and allowed the self-entanglement of the molecule. The equilibrium between the hermaphrodite molecule and the pseudo[1]rotaxane was studied by (1)H NMR spectroscopy: the best conditions of self-entanglement were found in the less polar solvent CD(2)Cl(2) and at high dilution. The triazole moiety was then benzylated to afford a benzyltriazolium moiety, which then played a dual role. On one hand, it acts as a bulky gate to trap the BMP25C8, thus to avoid any self-disentanglement of the molecular architecture. On another hand, it acts as a second molecular station for the macrocycle. At acidic pH, the BMP25C8 resides around the best anilinium molecular station, displaying the lasso [1]rotaxane in a loosened conformation. The deprotonation of the anilinium molecular station triggers the shuttling of the BMP25C8 around the triazolium moiety, therefore tightening the lasso.

  20. Molecular and Supramolecular Information Processing From Molecular Switches to Unconventional Computing

    CERN Document Server

    Katz, Evgeny

    2012-01-01

    Edited by a renowned and much cited chemist, this book covers the whole span of molecular computers that are based on non-biological systems. The contributions by all the major scientists in the field provide an excellent overview of the latest developments in this rapidly expanding area. A must-have for all researchers working on this very hot topic. Perfectly complements Biomolecular Information Processing, also by Prof. Katz, and available as a two-volume set.

  1. Conserving GW scheme for nonequilibrium quantum transport in molecular contacts

    DEFF Research Database (Denmark)

    Thygesen, Kristian Sommer; Rubio, Angel

    2008-01-01

    We give a detailed presentation of our recent scheme to include correlation effects in molecular transport calculations using the nonequilibrium Keldysh formalism. The scheme is general and can be used with any quasiparticle self-energy, but for practical reasons, we mainly specialize to the so-c...

  2. Photoisomerization dynamics of a rhodopsin-based molecule (potential molecular switch) with high quantum yields

    Science.gov (United States)

    Allen, Roland; Jiang, Chen-Wei; Zhang, Xiu-Xing; Fang, Ai-Ping; Li, Hong-Rong; Xie, Rui-Hua; Li, Fu-Li

    2015-03-01

    It is worthwhile to explore the detailed reaction dynamics of various candidates for molecular switches, in order to understand, e.g., the differences in quantum yields and switching times. Here we report density-functional-based simulations for the rhodopsin-based molecule 4-[4-Methylbenzylidene]-5-p-tolyl-3,4-dihydro-2H-pyrrole (MDP), synthesized by Sampedro et al. We find that the photoisomerization quantum yields are remarkably high: 82% for cis-to-trans, and 68% for trans-to-cis. The lifetimes of the S1 excited state in cis-MDP in our calculations are in the range of 900-1800 fs, with a mean value of 1270 fs, while the range of times required for full cis-to-trans isomerization are 1100-2000 fs, with a mean value of 1530 fs. In trans-MDP, the calculated S1 excited state lifetimes are 860-2140 fs, with a mean value of 1330 fs, and with the full trans-to-cis isomerization completed about 200 fs later. In both cases, the dominant reaction mechanism is rotation around the central C =C bond (connected to the pyrroline ring), and de-excitation occurs at an avoided crossing between the ground state and the lowest singlet state, near the midpoint of the rotational pathway. Research Fund for the Doctoral Program of Higher Education of China; Fundamental Research Funds for the Central Universities; Robert A. Welch Foundation; National Natural Science Foundation of China.

  3. Total synthesis of marinomycin A using salicylate as a molecular switch to mediate dimerization

    Science.gov (United States)

    Evans, P. Andrew; Huang, Mu-Hua; Lawler, Michael J.; Maroto, Sergio

    2012-08-01

    Antibiotics play a significant role in human health because of their ability to treat life-threatening bacterial infections. The growing problems with antibiotic resistance have made the development of new antibiotics a World Health Organization priority. Marinomycin A is a member of a new class of bis-salicylate-containing polyene macrodiolides, which have potent antibiotic activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. Herein, we describe a triply convergent synthesis of this agent using the salicylate as a novel molecular switch for the chemoselective construction of the macrodiolide. This strategy raises new questions regarding the biosynthetic role of the salicylate and its potential impact on the mechanism of action of these types of agents. For instance, in contrast to penicillin, which enhances the electrophilicity of the cyclic amide through ring strain, salicylates reduce the electrophilicity of the aryl ester through an intramolecular resonance-assisted hydrogen bond to provide an amide surrogate.

  4. Photochromic Spatiotemporal Control of Bubble-Propelled Micromotors by a Spiropyran Molecular Switch.

    Science.gov (United States)

    Moo, James Guo Sheng; Presolski, Stanislav; Pumera, Martin

    2016-03-22

    Controlling the environment in which bubble-propelled micromotors operate represents an attractive strategy to influence their motion, especially when the trigger is as simple as light. We demonstrate that spiropyrans, which isomerize to amphiphilic merocyanines under UV irradiation, can act as molecular switches that drastically affect the locomotion of the micrometer-sized engines. The phototrigger could be either a point or a field source, thus allowing different modes of control to be executed. A whole ensemble of micromotors was repeatedly activated and deactivated by just altering the spiropyran-merocyanine ratio with light. Moreover, the velocity of individual micromotors was altered using a point irradiation source that caused only localized changes in the environment. Such selective manipulation, achieved here with an optical microscope and a photochromic additive in the medium, reveals the ease of the methodology, which can allow micro- and nanomotors to reach their full potential of not just stochastic, but directional controlled motion.

  5. Photoinduced reversible switching of porosity in molecular crystals based on star-shaped azobenzene tetramers.

    Science.gov (United States)

    Baroncini, Massimo; d'Agostino, Simone; Bergamini, Giacomo; Ceroni, Paola; Comotti, Angiolina; Sozzani, Piero; Bassanetti, Irene; Grepioni, Fabrizia; Hernandez, Taylor M; Silvi, Serena; Venturi, Margherita; Credi, Alberto

    2015-08-01

    The development of solid materials that can be reversibly interconverted by light between forms with different physico-chemical properties is of great interest for separation, catalysis, optoelectronics, holography, mechanical actuation and solar energy conversion. Here, we describe a series of shape-persistent azobenzene tetramers that form porous molecular crystals in their E-configuration, the porosity of which can be tuned by changing the peripheral substituents on the molecule. Efficient E→Z photoisomerization of the azobenzene units takes place in the solid state and converts the crystals into a non-porous amorphous melt phase. Crystallinity and porosity are restored upon Z→E isomerization promoted by visible light irradiation or heating. We demonstrate that the photoisomerization enables reversible on/off switching of optical properties such as birefringence as well as the capture of CO2 from the gas phase. The linear design, structural versatility and synthetic accessibility make this new family of materials potentially interesting for technological applications.

  6. NBS-LRR Proteins and Their Partners: Molecular Switches of Plant Defense

    Institute of Scientific and Technical Information of China (English)

    LIU Chunyan; QIU Hongmei; WANG Jialin; WANG Jing; CHEN Qingshan; HU Guohua

    2008-01-01

    Specificity of the plant innate immune system is often conferred by resistance (R) proteins. Most plant disease resistance (R) proteins contain a series of leucine-rich repeats (LRRs), a nucleotide-binding site (NBS), and a putative amino-terminal signaling domain. They are termed NBS-LRR proteins. The LRRs are mainly involved in recognition, and the amino-terminal domain determines signaling specificity, whereas the NBS domain presumably functions as a molecular switch. During the past years, the most important discoveries are the role of partners in NBS-LRR gene mediated defenses, mounting support for the so-called "guard hypothesis" of R gene function, and providing evidence for intramolecular interactions and intelmolecular interactions within NBS-LRR proteins as a mode of signaling regulation. The outcome of these interactions determines whether a plant activates its defense responses.

  7. Retinoblastoma protein functions as a molecular switch determining white versus brown adipocyte differentiation

    DEFF Research Database (Denmark)

    Hansen, Jacob B; Jørgensen, Claus; Petersen, Rasmus K

    2004-01-01

    Adipocyte precursor cells give raise to two major cell populations with different physiological roles: white and brown adipocytes. Here we demonstrate that the retinoblastoma protein (pRB) regulates white vs. brown adipocyte differentiation. Functional inactivation of pRB in wild-type mouse embryo...... into adipocytes with a gene expression pattern and mitochondria content resembling brown adipose tissue. pRB-deficient MEFs exhibit an increased expression of the Forkhead transcription factor Foxc2 and its target gene cAMP-dependent protein kinase regulatory subunit RIalpha, resulting in increased c...... transdifferentiation of white into brown adipocytes in response to beta3-adrenergic receptor agonist treatment. We propose that pRB acts as a molecular switch determining white vs. brown adipogenesis, suggesting a previously uncharacterized function of this key cell cycle regulator in adipocyte lineage commitment...

  8. Thermodynamic Molecular Switch in Sequence-Specific Hydrophobic Interaction: Two Computational Models Compared

    Directory of Open Access Journals (Sweden)

    Paul Chun

    2003-01-01

    Full Text Available We have shown in our published work the existence of a thermodynamic switch in biological systems wherein a change of sign in ΔCp°(Treaction leads to a true negative minimum in the Gibbs free energy change of reaction, and hence, a maximum in the related Keq. We have examined 35 pair-wise, sequence-specific hydrophobic interactions over the temperature range of 273–333 K, based on data reported by Nemethy and Scheraga in 1962. A closer look at a single example, the pair-wise hydrophobic interaction of leucine-isoleucine, will demonstrate the significant differences when the data are analyzed using the Nemethy-Scheraga model or treated by the Planck-Benzinger methodology which we have developed. The change in inherent chemical bond energy at 0 K, ΔH°(T0 is 7.53 kcal mol-1 compared with 2.4 kcal mol-1, while ‹ts› is 365 K as compared with 355 K, for the Nemethy-Scheraga and Planck-Benzinger model, respectively. At ‹tm›, the thermal agitation energy is about five times greater than ΔH°(T0 in the Planck-Benzinger model, that is 465 K compared to 497 K in the Nemethy-Scheraga model. The results imply that the negative Gibbs free energy minimum at a well-defined ‹ts›, where TΔS° = 0 at about 355 K, has its origin in the sequence-specific hydrophobic interactions, which are highly dependent on details of molecular structure. The Nemethy-Scheraga model shows no evidence of the thermodynamic molecular switch that we have found to be a universal feature of biological interactions. The Planck-Benzinger method is the best known for evaluating the innate temperature-invariant enthalpy, ΔH°(T0, and provides for better understanding of the heat of reaction for biological molecules.

  9. Fundamental properties of molecules on surfaces. Molecular switching and interaction of magnetic molecules with superconductors

    Energy Technology Data Exchange (ETDEWEB)

    Hatter, Nino

    2016-12-14

    In this thesis, we investigate individual molecular switches and metal-organic complexes on surfaces with scanning tunneling microscopy (STM) and spectroscopy (STS) at low temperatures. One focus addresses the switching ability and mechanism of diarylethene on Ag(111). The other focus lies on resolving and tuning magnetic interactions of individual molecules with superconductors. 4,4'-(4,4'-(perfluorocyclopent-1-ene-1,2-diyl)bis (5-methylthiophene-4,2-diyl)dip yridine (PDTE) is a prototypical photochromic switch. We can induce a structural change of individual PDTE molecules on Ag(111) with the STM tip. This change is accompanied by a reduction of the energy gap between the occupied and unoccupied molecular orbitals. Density functional theory (DFT) calculations reveal that the induced switching corresponds to a ring-closing reaction from an open isomer in a flat adsorption configuration to a ring-closed isomer with its methyl groups in a cis configuration. The final product is thermodynamically stabilized by strong dispersion interactions with the surface. A linear dependence of the switching threshold with the tip-sample distance with a minimal threshold of 1.4 V is found, which we assign to a combination of an electric-field induced process and a tunneling-electron contribution. DFT calculations suggest a large activation barrier for a ring-closing reaction from the open flat configuration into the closed cis configuration. The interaction of magnetic molecules with superconductors is studied on manganese phthalocyanine (MnPc) adsorbed on Pb(111). We find triplets of Shiba states inside the superconducting gap. Different adsorption sites of MnPc provide a large variety of exchange coupling strengths, which lead to a collective energy shift of the Shiba triplets. We can assign the splitting of the Shiba states to be an effect of magnetic anisotropy in the system. A quantum phase transition from a ''Kondo screened'' to a &apos

  10. Controlling the color of cholesteric liquid-crystalline films by photoirradiation of a chiroptical molecular switch used as dopant

    NARCIS (Netherlands)

    van Delden, RA; Huck, NPM; Feringa, BL; Delden, Richard A. van; Gelder, Marc B. van; Huck, Nina P.M.

    2003-01-01

    Using thin films of a cholesteric mixture of acrylates 2 and 3 doped with the chiroptical molecular switch (M)-trans-1, photo-control of the reflection color between red and green is possible. This doped liquid-crystal (LC) film can be used for photoinduced writing, color reading, and photoinduced l

  11. Chiral induction in phenanthroline-derived oligoamide foldamers: an acid- and base-controllable switch in helical molecular strands.

    Science.gov (United States)

    Hu, Hai-Yu; Xiang, Jun-Feng; Yang, Yong; Chen, Chuan-Feng

    2008-03-20

    A series of phenanthroline-derived oligoamides bearing a chiral (R)-phenethylamino end group were synthesized that displayed chiral helical induction and subsequently formed one-hand helical foldamers in solution. Moreover, an acid- and base-controllable switch in the helical molecular strands was observed, which has been demonstrated by NMR, UV-vis, and circular dichroism spectroscopy.

  12. Synthesis of Hymecromone Derivatives Containing Chiral 1,1'-Bi-2-naphthyl Moiety for Dual-mode Molecular Switch

    Institute of Scientific and Technical Information of China (English)

    Zi Xing SHAN; Chun Guang XIAO

    2004-01-01

    Some hymecromone derivatives containing chiral 1,1(-bi-2-naphthyl moiety were synthesized and their photodimerizations were investigated.It was found that fluorescence intensity and optical rotation of the new chiral hymecromone derivatives could be regulated by light.This property has potential significance for developing a new type of dual-mode molecular switch.

  13. Isolation of Ion-Driven Conformations in Diphenylacetylene Molecular Switches Using Cryogenic Infrared Spectroscopy

    Science.gov (United States)

    Wolk, Arron B.; Garand, Etienne; Jones, Ian M.; Kamrath, Michael Z.; Hamilton, Rew; Johnson, Mark A.

    2012-06-01

    We report the infrared predissociation spectra of a family of ionic diphenylacetylene molecular switch complexes. The electrosprayed complexes were trapped and cooled in a cryogenic (10K) quadrupole ion trap and tagged with molecular deuterium. The infrared spectra of the vibrationally cold species reveal sharp transitions over a wide energy range (800 - 3800 cm-1), facilitating comparison to harmonic spectra. The evolution of the band pattern upon derivatization of the complexes exposes the signatures of the amide, urea, and carbonyl functionalities, enabling unambiguous identification of the non-covalent interactions that control the secondary structure of the molecule. Complexation with the tetramethylammonium cation reveals a conformation analogous to that of the neutral molecule, while halide ion attachment induces a conformational change similar to that observed earlier in solution. In several cases, both the donor and acceptor groups involved in the multidentate H-bonds are observed, providing a microscopic mechanical picture of the interactions at play. I. Jones, and A. Hamilton, Angew. Chem. Intl. Edit. 50, 4597 (2011).

  14. Ultrafast quenching of ring closure in molecular switches, self-assembled on gold nanoparticles

    NARCIS (Netherlands)

    Hania, Ralph; Pugžlys, Audrius; Kudernac, Tibor; Jonkman, Harry; Duppen, Koos; DeSilvestri, S.; Kobayashi, T.; Kobayashi, T.; Nelson, K.A.; Okada, T.

    2005-01-01

    We report the ultrafast quenching of the ring-closure reaction in BTE-based photochromic switches self-assembled on gold nanoparticles. The photoinduced population dynamics of the switches reveals that the electronic states of the switch molecules are strongly mixed with the states of the gold

  15. Ultrafast quenching of ring closure in molecular switches, self-assembled on gold nanoparticles

    NARCIS (Netherlands)

    Hania, Ralph; Pugžlys, Audrius; Kudernac, Tibor; Jonkman, Harry; Duppen, Koos; DeSilvestri, S.; Kobayashi, T.; Kobayashi, T.; Nelson, K.A.; Okada, T.

    2005-01-01

    We report the ultrafast quenching of the ring-closure reaction in BTE-based photochromic switches self-assembled on gold nanoparticles. The photoinduced population dynamics of the switches reveals that the electronic states of the switch molecules are strongly mixed with the states of the gold parti

  16. Mandibular arch muscle identity is regulated by a conserved molecular process during vertebrate development.

    Science.gov (United States)

    Knight, Robert D; Mebus, Katharina; Roehl, Henry H

    2008-06-15

    Vertebrate head muscles exhibit a highly conserved pattern of innervation and skeletal connectivity and yet it is unclear whether the molecular basis of their development is likewise conserved. Using the highly conserved expression of Engrailed 2 (En2) as a marker of identity in the dorsal mandibular muscles of zebrafish, we have investigated the molecular signals and tissues required for patterning these muscles. We show that muscle En2 expression is not dependent on signals from the adjacent neural tube, pharyngeal endoderm or axial mesoderm and that early identity of head muscles does not require bone morphogenetic pathway, Notch or Hedgehog (Hh) signalling. However, constrictor dorsalis En2 expression is completely lost after a loss of fibroblast growth factor (Fgf) signalling and we show that is true throughout head muscle development. These results suggest that head muscle identity is dependent on Fgf signalling. Data from experiments performed in chick suggest a similar regulation of En2 genes by Fgf signalling revealing a conserved mechanism for specifying head muscle identity. We present evidence that another key gene important in the development of mouse head muscles, Tbx1, is also critical for specification of mandibular arch muscle identity and that this is independent of Fgf signalling. These data imply that dorsal mandibular arch muscle identity in fish, chick and mouse is specified by a highly conserved molecular process despite differing functions of these muscles in different lineages.

  17. Ultrafast in cellulo photoinduced dynamics processes of the paradigm molecular light switch [Ru(bpy)2dppz](2.).

    Science.gov (United States)

    De la Cadena, Alejandro; Davydova, Dar'ya; Tolstik, Tatiana; Reichardt, Christian; Shukla, Sapna; Akimov, Denis; Heintzmann, Rainer; Popp, Jürgen; Dietzek, Benjamin

    2016-09-20

    An in cellulo study of the ultrafast excited state processes in the paradigm molecular light switch [Ru(bpy)2dppz](2+) by localized pump-probe spectroscopy is reported for the first time. The localization of [Ru(bpy)2dppz](2+) in HepG2 cells is verified by emission microscopy and the characteristic photoinduced picosecond dynamics of the molecular light switch is observed in cellulo. The observation of the typical phosphorescence stemming from a (3)MLCT state suggests that the [Ru(bpy)2dppz](2+) complex intercalates with the DNA in the nucleus. The results presented for this benchmark coordination compound reveal the necessity to study the photoinduced processes in coordination compounds for intracellular use, e.g. as sensors or as photodrugs, in the actual biological target environment in order to derive a detailed molecular mechanistic understanding of the excited-state properties of the systems in the actual biological target environment.

  18. Ultrafast in cellulo photoinduced dynamics processes of the paradigm molecular light switch [Ru(bpy)2dppz]2+

    Science.gov (United States)

    De la Cadena, Alejandro; Davydova, Dar’ya; Tolstik, Tatiana; Reichardt, Christian; Shukla, Sapna; Akimov, Denis; Heintzmann, Rainer; Popp, Jürgen; Dietzek, Benjamin

    2016-01-01

    An in cellulo study of the ultrafast excited state processes in the paradigm molecular light switch [Ru(bpy)2dppz]2+ by localized pump-probe spectroscopy is reported for the first time. The localization of [Ru(bpy)2dppz]2+ in HepG2 cells is verified by emission microscopy and the characteristic photoinduced picosecond dynamics of the molecular light switch is observed in cellulo. The observation of the typical phosphorescence stemming from a 3MLCT state suggests that the [Ru(bpy)2dppz]2+ complex intercalates with the DNA in the nucleus. The results presented for this benchmark coordination compound reveal the necessity to study the photoinduced processes in coordination compounds for intracellular use, e.g. as sensors or as photodrugs, in the actual biological target environment in order to derive a detailed molecular mechanistic understanding of the excited-state properties of the systems in the actual biological target environment. PMID:27644587

  19. Ultrafast in cellulo photoinduced dynamics processes of the paradigm molecular light switch [Ru(bpy)2dppz]2+

    Science.gov (United States)

    de La Cadena, Alejandro; Davydova, Dar'Ya; Tolstik, Tatiana; Reichardt, Christian; Shukla, Sapna; Akimov, Denis; Heintzmann, Rainer; Popp, Jürgen; Dietzek, Benjamin

    2016-09-01

    An in cellulo study of the ultrafast excited state processes in the paradigm molecular light switch [Ru(bpy)2dppz]2+ by localized pump-probe spectroscopy is reported for the first time. The localization of [Ru(bpy)2dppz]2+ in HepG2 cells is verified by emission microscopy and the characteristic photoinduced picosecond dynamics of the molecular light switch is observed in cellulo. The observation of the typical phosphorescence stemming from a 3MLCT state suggests that the [Ru(bpy)2dppz]2+ complex intercalates with the DNA in the nucleus. The results presented for this benchmark coordination compound reveal the necessity to study the photoinduced processes in coordination compounds for intracellular use, e.g. as sensors or as photodrugs, in the actual biological target environment in order to derive a detailed molecular mechanistic understanding of the excited-state properties of the systems in the actual biological target environment.

  20. Molecular Design of Ionization-Induced Proton Switching Element Based on Fluorinated DNA Base Pair.

    Science.gov (United States)

    Tachikawa, Hiroto; Kawabata, Hiroshi

    2016-03-10

    To design theoretically the high-performance proton switching element based on DNA base pair, the effects of fluorine substitution on the rate of proton transfer (PT) in the DNA model base pair have been investigated by means of direct ab initio molecular dynamics (AIMD) method. The 2-aminopyridine dimer, (AP)2, was used as the model of the DNA base pair. One of the hydrogen atoms of the AP molecule in the dimer was substituted by a fluorine (F) atom, and the structures of the dimer, expressed by F-(AP)2, were fully optimized at the MP2/6-311++G(d,p) level. The direct AIMD calculations showed that the proton is transferred within the base pair after the vertical ionization. The rates of PT in F-(AP)2(+) were calculated and compared with that of (AP)2(+) without an F atom. It was found that PT rate is accelerated by the F-substitution. Also, the direction of PT between F-AP and AP molecules can be clearly controlled by the position of F-substitution (AP)2 in the dimer.

  1. Temperature control of molecular circuit switch responsible for virulent phenotype expression in uropathogenic Escherichia coli

    Science.gov (United States)

    Samoilov, Michael

    2010-03-01

    The behavior and fate of biological organisms are to a large extent dictated by their environment, which can be often viewed as a collection of features and constraints governed by physics laws. Since biological systems comprise networks of molecular interactions, one such key physical property is temperature, whose variations directly affect the rates of biochemical reactions involved. For instance, temperature is known to control many gene regulatory circuits responsible for pathogenicity in bacteria. One such example is type 1 fimbriae (T1F) -- the foremost virulence factor in uropathogenic E. coli (UPEC), which accounts for 80-90% of all community-acquired urinary tract infections (UTIs). The expression of T1F is randomly `phase variable', i.e. individual cells switch between virulent/fimbriate and avirulent/afimbriate phenotypes, with rates regulated by temperature. Our computational investigation of this process, which is based on FimB/FimE recombinase-mediated inversion of fimS DNA element, offers new insights into its discrete-stochastic kinetics. In particular, it elucidates the logic of T1F control optimization to the host temperature and contributes further understanding toward the development of novel therapeutic approaches to UPEC-caused UTIs.

  2. A cytosolic carbonic anhydrase molecular switch occurs in the gills of metamorphic sea lamprey

    Science.gov (United States)

    Ferreira-Martins, D.; McCormick, Stephen; Campos, A.; Lopes-Marques, M.; Osorio, H.; Coimbra, J.; Castro, L.F.C.; Wilson, Jonthan M

    2016-01-01

    Carbonic anhydrase plays a key role in CO2 transport, acid-base and ion regulation and metabolic processes in vertebrates. While several carbonic anhydrase isoforms have been identified in numerous vertebrate species, basal lineages such as the cyclostomes have remained largely unexamined. Here we investigate the repertoire of cytoplasmic carbonic anhydrases in the sea lamprey (Petromyzon marinus), that has a complex life history marked by a dramatic metamorphosis from a benthic filter-feeding ammocoete larvae into a parasitic juvenile which migrates from freshwater to seawater. We have identified a novel carbonic anhydrase gene (ca19) beyond the single carbonic anhydrase gene (ca18) that was known previously. Phylogenetic analysis and synteny studies suggest that both carbonic anhydrase genes form one or two independent gene lineages and are most likely duplicates retained uniquely in cyclostomes. Quantitative PCR of ca19 and ca18 and protein expression in gill across metamorphosis show that the ca19 levels are highest in ammocoetes and decrease during metamorphosis while ca18 shows the opposite pattern with the highest levels in post-metamorphic juveniles. We propose that a unique molecular switch occurs during lamprey metamorphosis resulting in distinct gill carbonic anhydrases reflecting the contrasting life modes and habitats of these life-history stages.

  3. A novel colorimetric triple-helix molecular switch aptasensor for ultrasensitive detection of tetracycline.

    Science.gov (United States)

    Ramezani, Mohammad; Mohammad Danesh, Noor; Lavaee, Parirokh; Abnous, Khalil; Mohammad Taghdisi, Seyed

    2015-08-15

    Detection methods of antibiotic residues in blood serum and animal derived foods are of great interest. In this study a colorimetric aptasensor was designed for sensitive, selective and fast detection of tetracycline based on triple-helix molecular switch (THMS) and gold nanoparticles (AuNPs). As a biosensor, THMS shows distinct advantages including high stability, sensitivity and preserving the selectivity and affinity of the original aptamer. In the absence of tetracycline, THMS is stable, leading to the aggregation of AuNPs by salt and an obvious color change from red to blue. In the presence of tetracycline, aptamer binds to its target, signal transduction probe (STP) leaves the THMS and adsorbs on the surface of AuNPs. So the well-dispersed AuNPs remain stable against salt-induced aggregation with a red color. The presented aptasensor showed high selectivity toward tetracyclines with a limit of detection as low as 266 pM for tetracycline. The designed aptasensor was successfully applied to detect tetracycline in serum and milk.

  4. Ultrafast quantum spin-state switching in the Co-octaethylporphyrin molecular magnet with a terahertz pulsed magnetic field

    Science.gov (United States)

    Farberovich, Oleg V.; Mazalova, Victoria L.

    2016-05-01

    Molecular spin crossover switches are the objects of intense theoretical and experimental studies in recent years. This interest is due to the fact that these systems allow one to control their spin state by applying an external photo-, thermo-, piezo-, or magnetic stimuli. The greatest amount of research is currently devoted to the study of the effect of the photoexcitation on the bi-stable states of spin crossover single molecular magnets (SMMs). The main limitation of photo-induced bi-stable states is their short lifetime. In this paper we present the results of a study of the spin dynamics of the Co-octaethylporphyrin (CoOEP) molecule in the Low Spin (LS) state and the High Spin (HS) state induced by applying the magnetic pulse of 36.8 T. We show that the spin switching in case of the HS state of the CoOEP molecule is characterized by a long lifetime and is dependent on the magnitude and duration of the applied field. Thus, after applying an external stimuli the system in the LS state after the spin switching reverts to its ground state, whereas the system in the HS state remains in the excited state for a long time. We found that the temperature dependency of magnetic susceptibility shows an abrupt thermal spin transition between two spin states at 40 K. Here the proposed theoretical approach opens the way to create modern devices for spintronics with the controllable spin switching process.

  5. Multilayered proteomics reveals molecular switches dictating ligand-dependent EGFR trafficking

    DEFF Research Database (Denmark)

    Francavilla, Chiara; Papetti, Moreno; Rigbolt, Kristoffer T G

    2016-01-01

    identified RAB7 phosphorylation and RCP recruitment to EGFR as switches for EGF and TGF-α outputs, controlling receptor trafficking, signaling duration, proliferation, and migration. By manipulating RCP levels or phosphorylation of RAB7 in EGFR-positive cancer cells, we were able to switch a TGF...

  6. Isomerization of Orthogonal Molecular Switches Encapsulated within Micelles Solubilizing Carbon Nanotubes

    DEFF Research Database (Denmark)

    Kreft, Stefanie K.; Petersen, Michael Åxman; Nielsen, Mogens Brøndsted

    2015-01-01

    We study the effects of the proximity of the orthogonal dipole-switching moiety dihydroazulene/vinylheptafulvene (DHA/VHF) to carbon nanotubes (CNTs). The switches are introduced into a micelle surrounding the CNTs, thereby achieving very close proximity between the molecules and the CNTs for the...

  7. Programmable DNA triple-helix molecular switch in biosensing applications: from in homogenous solutions to in living cells.

    Science.gov (United States)

    Tang, Pinting; Zheng, Jing; Tang, Jianru; Ma, Dandan; Xu, Weijian; Li, Jishan; Cao, Zhong; Yang, Ronghua

    2017-02-21

    Herein, we demonstrated a new gold nanoparticles (AuNPs)-integrated programmable triple-helix molecular switch (THMS) to realize the biosensing of multiple targets from in homogenous solution to in living cells. The results demonstrated that this proposed programmable THMS could be successfully used for imaging multiple messenger RNA (mRNA) in living cells and it significantly extends the scope of the THMS sensing platform.

  8. A Redox-Controllable Molecular Switch Based on Weak Recognition of BPX26C6 at a Diphenylurea Station

    Directory of Open Access Journals (Sweden)

    Jia-Cheng Chang

    2015-01-01

    Full Text Available The Na+ ion–assisted recognition of urea derivatives by BPX26C6 has allowed the construction of a redox-controllable [2]rotaxane-type molecular switch based on two originally very weakly interacting host/guest systems. Using NOBF4 to oxidize the triarylamine terminus into a corresponding radical cation attracted the macrocyclic component toward its adjacent carbamate station; subsequent addition of Zn powder moved the macrocyclic component back to its urea station.

  9. Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway

    DEFF Research Database (Denmark)

    Amit, Sharon; Hatzubai, Ada; Birman, Yaara;

    2002-01-01

    The Wnt pathway controls numerous developmental processes via the beta-catenin-TCF/LEF transcription complex. Deregulation of the pathway results in the aberrant accumulation of beta-catenin in the nucleus, often leading to cancer. Normally, cytoplasmic beta-catenin associates with APC and axin a......, thereby precluding the initiation of the cascade. Thus, a single, CKI-dependent phosphorylation event serves as a molecular switch for the Wnt pathway. Udgivelsesdato: 2002-May-1...

  10. Surface migration of molecular adsorbates revisited: Morse-potential modeling based on bond-order conservation

    Science.gov (United States)

    Shustorovich, Evgeny

    1985-11-01

    Our bond-order-conservation model of surface migration of molecular AB adsorbates [J. Am. Chem. Soc. 106 (1984) 6479] has been generalized to provide for A-B bond-order changes under migration and to search for energy stationary points. The results are rigorous and well defined. The new conclusions corroborate most of the previous findings but also lead to important corrections (e.g., the mogration patterns of donor molecules) and new projections (e.g., monotonic destabilization of AB as its coordination increases without direct relevance to the heat of chemisorption and simple interrelations between molecular and atomic heats of chemisorption), in agreement with experiment.

  11. Aptamer contained triple-helix molecular switch for rapid fluorescent sensing of acetamiprid.

    Science.gov (United States)

    Liu, Xin; Li, Ying; Liang, Jing; Zhu, Wenyue; Xu, Jingyue; Su, Ruifang; Yuan, Lei; Sun, Chunyan

    2016-11-01

    In this study, an aptamer-based fluorescent sensing platform using triple-helix molecular switch (THMS) was developed for the pesticide screening represented by acetamiprid. The THMS was composed of two tailored DNA probes: a label-free central target specific aptamer sequence flanked by two arm segments acting as a recognition probe; a hairpin-shaped structure oligonucleotide serving as a signal transduction probe (STP), labeled with a fluorophore and a quencher at the 3' and 5'-end, respectively. In the absence of acetamiprid, complementary bindings of two arm segments of the aptamers with the loop sequence of STP enforce the formation of THMS with the "open" configuration of STP, and the fluorescence of THMS is on. In the presence of target acetamiprid, the aptamer-target binding results in the formation of a structured aptamer/target complex, which disassembles the THMS and releases the STP. The free STP is folded to a stem loop structure, and the fluorescence is quenched. The quenched fluorescence intensity was proportional to the concentration of acetamiprid in the range from 100 to 1200nM, with the limit of detection (LOD) as low as 9.12nM. In addition, this THMS-based method has been successfully used to test and quantify acetamiprid in Chinese cabbage with satisfactory recoveries, and the results were in full agreement with those from LC-MS. The aptamer-based THMS presents distinct advantages, including high stability, remarkable sensitivity, and preservation of the affinity and specificity of the original aptamer. Most importantly, this strategy is convenient and generalizable by virtue of altering the aptamer sequence without changing the triple-helix structure. So, it is expected that this aptamer-based fluorescent assay could be extensively applied in the field of food safety inspection.

  12. A sensitive SERS assay for detecting proteins and nucleic acids using a triple-helix molecular switch for cascade signal amplification.

    Science.gov (United States)

    Ye, Sujuan; Wu, Yanying; Zhang, Wen; Li, Na; Tang, Bo

    2014-08-25

    A novel surface-enhanced Raman scattering (SERS) detection system is developed for proteins and nucleic acids based on a triple-helix molecular switch for multiple cycle signal amplification, achieving high sensitivity, universality, rapid analysis, and high selectivity.

  13. Ab initio study of transport properties of an all-carbon molecular switch based on C20 molecule

    Institute of Scientific and Technical Information of China (English)

    OUYANG Fang-ping; XU Hui

    2007-01-01

    Choosing closed-ended armchair (5, 5) singlewall carbon nanotubes (CCNTs) as electrodes, we have investigated the electron transport properties across a carbon molecular junction consisting of a C20 molecule sandwiched between two semi-infinite carbon nanotubes. It is shown that the Landauer conductance of this carbon hybrid system can be tuned within several orders of magnitude not only by varying the tube-C20 distance, but more importantly by changing the orientation of the C20 molecule and rotating the C20 molecule or one of the tubes around the symmetry axis of the system at fixed distances. This fact could make this all-carbon molecular system a possible candidate for a nanoelectronic switching device. Moreover, our study also reveals that molecular configuration selection and structural relaxation would play an important role in the design of such devices.

  14. Speeding up Monte Carlo molecular simulation by a non-conservative early rejection scheme

    KAUST Repository

    Kadoura, Ahmad Salim

    2015-04-23

    Monte Carlo (MC) molecular simulation describes fluid systems with rich information, and it is capable of predicting many fluid properties of engineering interest. In general, it is more accurate and representative than equations of state. On the other hand, it requires much more computational effort and simulation time. For that purpose, several techniques have been developed in order to speed up MC molecular simulations while preserving their precision. In particular, early rejection schemes are capable of reducing computational cost by reaching the rejection decision for the undesired MC trials at an earlier stage in comparison to the conventional scheme. In a recent work, we have introduced a ‘conservative’ early rejection scheme as a method to accelerate MC simulations while producing exactly the same results as the conventional algorithm. In this paper, we introduce a ‘non-conservative’ early rejection scheme, which is much faster than the conservative scheme, yet it preserves the precision of the method. The proposed scheme is tested for systems of structureless Lennard-Jones particles in both canonical and NVT-Gibbs ensembles. Numerical experiments were conducted at several thermodynamic conditions for different number of particles. Results show that at certain thermodynamic conditions, the non-conservative method is capable of doubling the speed of the MC molecular simulations in both canonical and NVT-Gibbs ensembles. © 2015 Taylor & Francis

  15. Reversible molecular switching at a metal surface: A case study of tetra- tert-butyl-azobenzene on Au(1 1 1)

    Science.gov (United States)

    Wolf, Martin; Tegeder, Petra

    2009-06-01

    Molecular switches represent a fascinating class of functional molecules, whose properties can be reversibly changed between different molecular states by excitation with light or other external stimuli. Using surface science concepts like self assembly to align such molecules in a well-defined geometry at solid surfaces, new functional properties may arise, which are relevant for different fields like, e.g., molecular electronics, sensing or biocompatible interfaces. For a microscopic understanding of molecular switching at surfaces, it is essential to obtain detailed knowledge on the underlying elementary processes, for instance the excitation mechanism in photoinduced switching. Here we present a case study of a specifically designed azobenzene derivative on a metal surface, namely tetra- tert-butyl-azobenzene (TBA) adsorbed on Au(1 1 1), which is so far one of the best studied system for which reversible conformational changes have been demonstrated. TBA/Au(1 1 1) can thus be viewed as model system in order to gain deeper insights into molecular switching processes at metal surfaces. We have studied the photoinduced and thermally activated reversible switching of TBA in direct contact with a Au(1 1 1) surface using two-photon photoemission (2PPE) and high-resolution electron energy loss spectroscopy (HREELS). The trans/cis-isomerization of TBA is accompanied by reversible changes in the geometrical and electronic structure of the molecules, allowing to gain mechanistic and quantitative insight into the switching process. In particular, the cross sections for the photoisomerization, the ratio between the cis- and trans-TBA in the photostationary state, and the activation energy for the thermally induced cis→trans reaction have been determined and are found to be strongly reduced compared to the corresponding quantities in the liquid phase. Furthermore, the mechanism of optical excitation and molecular switching of TBA on Au(1 1 1) has been identified to arise

  16. Single electron bipolar conductance switch driven by the molecular Aharonov-Bohm effect.

    Science.gov (United States)

    Lee, Joonhee; Tallarida, Nicholas; Rios, Laura; Perdue, Shawn M; Apkarian, Vartkess Ara

    2014-06-24

    We demonstrate a conductance switch controlled by the spin-vibronic density of an odd electron on a single molecule. The junction current is modulated by the spin-flip bistability of the electron. Functional images are provided as wiring diagrams for control of the switch's frequency, amplitude, polarity, and duty-cycle. The principle of operation relies on the quantum mechanical phase associated with the adiabatic circulation of a spin-aligned electron around a conical intersection. The functional images quantify the governing vibronic Hamiltonian.

  17. Conservation biological control of pests in the molecular era: new opportunities to address old constraints

    Directory of Open Access Journals (Sweden)

    Gurr eGeoff

    2016-01-01

    Full Text Available ABSTRACTBiological control has long been considered a potential alternative to pesticidal strategies for pest management but its impact and level of use globally remain modest and inconsistent. A rapidly expanding range of molecular – particularly DNA-related – techniques is currently revolutionizing many life sciences. This review identifies a series of constraints on the development and uptake of conservation biological control and considers the contemporary and likely future influence of molecular methods on these constraints. Molecular approaches are now often used to complement morphological taxonomic methods for the identification and study of biological control agents including microbes. A succession of molecular techniques has been applied to ‘who eats whom’ questions in food-web ecology. Polymerase chain reaction (PCR approaches have largely superseded immunological approaches such as enzyme-linked immunosorbent assay (ELISA and now – in turn – are being overtaken by next generation sequencing (NGS- based approaches that offer unparalleled power at a rapidly diminishing cost. There is scope also to use molecular techniques to manipulate biological control agents, which will be accelerated with the advent of gene editing tools, the CRISPR/Cas9 system in particular. Gene editing tools also offer unparalleled power to both elucidate and manipulate the plant defence mechanisms including those that involve natural enemy attraction to attacked plants. Rapid advances in technology will allow the development of still more novel pest management options for which uptake is likely to be limited chiefly by regulatory hurdles.

  18. Transition metal functionalized photo- and redox-switchable diarylethene based molecular switches

    NARCIS (Netherlands)

    Harvey, Emma C.; Feringa, Ben L.; Vos, Johannes G.; Browne, Wesley R.; Pryce, Mary T.

    2015-01-01

    In this review recent progress in combining metal carbonyl and bipyridyl transition metal complexes with dithienylethene photochromic switches is discussed. A key challenge in designing such systems is to allow for interaction between the various components, but without loss in photochemical activit

  19. Emerging roles of microRNAs as molecular switches in the integrated circuit of the cancer cell

    Science.gov (United States)

    Sotiropoulou, Georgia; Pampalakis, Georgios; Lianidou, Evi; Mourelatos, Zissimos

    2009-01-01

    Transformation of normal cells into malignant tumors requires the acquisition of six hallmark traits, e.g., self-sufficiency in growth signals, insensitivity to antigrowth signals and self-renewal, evasion of apoptosis, limitless replication potential, angiogenesis, invasion, and metastasis, which are common to all cancers (Hanahan and Weinberg 2000). These new cellular traits evolve from defects in major regulatory microcircuits that are fundamental for normal homeostasis. The discovery of microRNAs (miRNAs) as a new class of small non-protein-coding RNAs that control gene expression post-transcriptionally by binding to various mRNA targets suggests that these tiny RNA molecules likely act as molecular switches in the extensive regulatory web that involves thousands of transcripts. Most importantly, accumulating evidence suggests that numerous microRNAs are aberrantly expressed in human cancers. In this review, we discuss the emergent roles of microRNAs as switches that function to turn on/off known cellular microcircuits. We outline recent compelling evidence that deregulated microRNA-mediated control of cellular microcircuits cooperates with other well-established regulatory mechanisms to confer the hallmark traits of the cancer cell. Furthermore, these exciting insights into aberrant microRNA control in cancer-associated circuits may be exploited for cancer therapies that will target deregulated miRNA switches. PMID:19561119

  20. Electrostatic Switch Function in the Mechanism of Protein Kinase A Iα Activation: Results of the Molecular Dynamics Simulation

    Science.gov (United States)

    Rogacheva, Olga N.; Shchegolev, Boris F.

    2017-01-01

    We used molecular dynamics to find the average path of the A-domain H → B conformational transition in protein kinase A Iα. We obtained thirteen productive trajectories and processed them sequentially using factor and cross-correlation analyses. The conformational transition is presented as partly deterministic sequence of six events. Event B represents H → B transition of the phosphate binding cassette. Main participants of this event form electrostatic switch cAMP(O6)–A202(N-H)–G199(C=O). Through this switch, cAMP transmits information about its binding to hydrophobic switch L203–Y229 and thus triggers conformational transition of A-domain. Events C and D consist in N3A-motif displacement towards phosphate binding cassette and B/C-helix rotation. Event E involves an increase in interaction energy between Y229 and β-subdomain. Taken together, events B, E, and D correspond to the hinge movement towards β-barrel. Transition of B/C-helix turn (a.a. 229–234) from α-form to π-form accounts for event F. Event G implies that π-helical turn is replaced by kink. Emerging in the resulting conformation, electrostatic interaction R241–E200 facilitates kink formation. The obtained data on the mechanism of cAMP-dependent activation of PKA Iα may contribute to new approaches to designing pharmaceuticals based on cAMP analogs.

  1. A conserved aromatic lock for the tryptophan rotameric switch in TM-VI of seven-transmembrane receptors

    DEFF Research Database (Denmark)

    Holst, Birgitte; Nygaard, Rie; Hansen, Louise Valentin;

    2010-01-01

    simulations in rhodopsin demonstrated that rotation around the chi1 torsion angle of Trp-VI:13 brings its side chain close to the equally highly conserved Phe-V:13 (Phe-5.47) in TM-V. In the ghrelin receptor, engineering of high affinity metal-ion sites between these positions confirmed their close spatial...

  2. Energetic pulses in exciton-phonon molecular chains and conservative numerical methods for quasilinear Hamiltonian systems.

    Science.gov (United States)

    Lemesurier, Brenton

    2013-09-01

    The phenomenon of coherent energetic pulse propagation in exciton-phonon molecular chains such as α-helix protein is studied using an ODE system model of Davydov-Scott type, both with numerical studies using a new unconditionally stable fourth-order accurate energy-momentum conserving time discretization and with analytical explanation of the main numerical observations. Impulsive initial data associated with initial excitation of a single amide-I vibration by the energy released by ATP hydrolysis are used as well as the best current estimates of physical parameter values. In contrast to previous studies based on a proposed long-wave approximation by the nonlinear Schrödinger (NLS) equation and focusing on initial data resembling the soliton solutions of that equation, the results here instead lead to approximation by the third derivative nonlinear Schrödinger equation, giving a far better fit to observed behavior. A good part of the behavior is indeed explained well by the linear part of that equation, the Airy PDE, while other significant features do not fit any PDE approximation but are instead explained well by a linearized analysis of the ODE system. A convenient method is described for construction of the highly stable, accurate conservative time discretizations used, with proof of its desirable properties for a large class of Hamiltonian systems, including a variety of molecular models.

  3. A conservative and a hybrid early rejection schemes for accelerating Monte Carlo molecular simulation

    KAUST Repository

    Kadoura, Ahmad Salim

    2014-03-17

    Molecular simulation could provide detailed description of fluid systems when compared to experimental techniques. They can also replace equations of state; however, molecular simulation usually costs considerable computational efforts. Several techniques have been developed to overcome such high computational costs. In this paper, two early rejection schemes, a conservative and a hybrid one, are introduced. In these two methods, undesired configurations generated by the Monte Carlo trials are rejected earlier than it would when using conventional algorithms. The methods are tested for structureless single-component Lennard-Jones particles in both canonical and NVT-Gibbs ensembles. The computational time reduction for both ensembles is observed at a wide range of thermodynamic conditions. Results show that computational time savings are directly proportional to the rejection rate of Monte Carlo trials. The proposed conservative scheme has shown to be successful in saving up to 40% of the computational time in the canonical ensemble and up to 30% in the NVT-Gibbs ensemble when compared to standard algorithms. In addition, it preserves the exact Markov chains produced by the Metropolis scheme. Further enhancement for NVT-Gibbs ensemble is achieved by combining this technique with the bond formation early rejection one. The hybrid method achieves more than 50% saving of the central processing unit (CPU) time.

  4. Molecular mediators for raft-dependent endocytosis of syndecan-1, a highly conserved, multifunctional receptor.

    Science.gov (United States)

    Chen, Keyang; Williams, Kevin Jon

    2013-05-17

    Endocytosis via rafts has attracted considerable recent interest, but the molecular mediators remain incompletely characterized. Here, we focused on the syndecan-1 heparan sulfate proteoglycan, a highly conserved, multifunctional receptor that we previously showed to undergo raft-dependent endocytosis upon clustering. Alanine scanning mutagenesis of three to five consecutive cytoplasmic residues at a time revealed that a conserved juxtamembrane motif, MKKK, was the only region required for efficient endocytosis after clustering. Endocytosis of clustered syndecan-1 occurs in two phases, each requiring a kinase and a corresponding cytoskeletal partner. In the initial phase, ligands trigger rapid MKKK-dependent activation of ERK and the localization of syndecan-1 into rafts. Activation of ERK drives the dissociation of syndecan-1 from α-tubulin, a molecule that may act as an anchor for syndecan-1 at the plasma membrane in the basal state. In the second phase, Src family kinases phosphorylate tyrosyl residues within the transmembrane and cytoplasmic regions of syndecan-1, a process that also requires MKKK. Tyrosine phosphorylation of syndecan-1 triggers the robust recruitment of cortactin, which we found to be an essential mediator of efficient actin-dependent endocytosis. These findings represent the first detailed characterization of the molecular events that drive endocytosis of a raft-dependent receptor and identify a novel endocytic motif, MKKK. Moreover, the results provide new tools to study syndecan function and regulation during uptake of its biologically and medically important ligands, such as HIV-1, atherogenic postprandial remnant lipoproteins, and molecules implicated in Alzheimer disease.

  5. Molecular Switch for Sub-Diffraction Laser Lithography by Photoenol Intermediate-State Cis-Trans Isomerization.

    Science.gov (United States)

    Mueller, Patrick; Zieger, Markus M; Richter, Benjamin; Quick, Alexander S; Fischer, Joachim; Mueller, Jonathan B; Zhou, Lu; Nienhaus, Gerd Ulrich; Bastmeyer, Martin; Barner-Kowollik, Christopher; Wegener, Martin

    2017-06-27

    Recent developments in stimulated-emission depletion (STED) microscopy have led to a step change in the achievable resolution and allowed breaking the diffraction limit by large factors. The core principle is based on a reversible molecular switch, allowing for light-triggered activation and deactivation in combination with a laser focus that incorporates a point or line of zero intensity. In the past years, the concept has been transferred from microscopy to maskless laser lithography, namely direct laser writing (DLW), in order to overcome the diffraction limit for optical lithography. Herein, we propose and experimentally introduce a system that realizes such a molecular switch for lithography. Specifically, the population of intermediate-state photoenol isomers of α-methyl benzaldehydes generated by two-photon absorption at 700 nm fundamental wavelength can be reversibly depleted by simultaneous irradiation at 440 nm, suppressing the subsequent Diels-Alder cycloaddition reaction which constitutes the chemical core of the writing process. We demonstrate the potential of the proposed mechanism for STED-inspired DLW by covalently functionalizing the surface of glass substrates via the photoenol-driven STED-inspired process exploiting reversible photoenol activation with a polymerization initiator. Subsequently, macromolecules are grown from the functionalized areas and the spatially coded glass slides are characterized by atomic-force microscopy. Our approach allows lines with a full-width-at-half-maximum of down to 60 nm and line gratings with a lateral resolution of 100 nm to be written, both surpassing the diffraction limit.

  6. Evolutionary, behavioural and molecular ecology must meet to achieve long-term conservation goals.

    Science.gov (United States)

    Keogh, J Scott

    2009-09-01

    Founder populations in reintroduction programmes can experience a genetic bottleneck simply because of their small size. The influence of reproductive skew brought on by polygynous or polyandrous mating systems in these populations can exacerbate already difficult conservation genetic problems, such as inbreeding depression and loss of adaptive potential. Without an understanding of reproductive skew in a target species, and the effect it can have on genetic diversity retained over generations, long-term conservation goals will be compromised. In this issue of Molecular Ecology, Miller et al. (2009a) test how founder group size and variance in male reproductive success influence the maintenance of genetic diversity following reintroduction on a long-term scale. They evaluated genetic diversity in two wild populations of the iconic New Zealand tuatara (Fig. 1), which differ greatly in population size and genetic diversity, and compared this to genetic diversity in multiple founder populations sourced from both populations. Population viability analysis on the maintenance of genetic diversity over 400 years (10 generations) demonstrated that while the loss of heterozygosity was low when compared with both source populations (1-14%), the greater the male reproductive skew, the greater the predicted losses of genetic diversity. Importantly however, the loss of genetic diversity was ameliorated after population size exceeded 250 animals, regardless of the level of reproductive skew. This study demonstrates that highly informed conservation decisions could be made when you build on a solid foundation of demographic, natural history and behavioural ecology data. These data, when informed by modern population and genetic analysis, mean that fundamental applied conservation questions (how many animals should make up a founder population?) can be answered accurately and with an eye to the long-term consequences of management decisions.

  7. MOIL-opt: Energy-Conserving Molecular Dynamics on a GPU/CPU system.

    Science.gov (United States)

    Ruymgaart, A Peter; Cardenas, Alfredo E; Elber, Ron

    2011-08-26

    We report an optimized version of the molecular dynamics program MOIL that runs on a shared memory system with OpenMP and exploits the power of a Graphics Processing Unit (GPU). The model is of heterogeneous computing system on a single node with several cores sharing the same memory and a GPU. This is a typical laboratory tool, which provides excellent performance at minimal cost. Besides performance, emphasis is made on accuracy and stability of the algorithm probed by energy conservation for explicit-solvent atomically-detailed-models. Especially for long simulations energy conservation is critical due to the phenomenon known as "energy drift" in which energy errors accumulate linearly as a function of simulation time. To achieve long time dynamics with acceptable accuracy the drift must be particularly small. We identify several means of controlling long-time numerical accuracy while maintaining excellent speedup. To maintain a high level of energy conservation SHAKE and the Ewald reciprocal summation are run in double precision. Double precision summation of real-space non-bonded interactions improves energy conservation. In our best option, the energy drift using 1fs for a time step while constraining the distances of all bonds, is undetectable in 10ns simulation of solvated DHFR (Dihydrofolate reductase). Faster options, shaking only bonds with hydrogen atoms, are also very well behaved and have drifts of less than 1kcal/mol per nanosecond of the same system. CPU/GPU implementations require changes in programming models. We consider the use of a list of neighbors and quadratic versus linear interpolation in lookup tables of different sizes. Quadratic interpolation with a smaller number of grid points is faster than linear lookup tables (with finer representation) without loss of accuracy. Atomic neighbor lists were found most efficient. Typical speedups are about a factor of 10 compared to a single-core single-precision code.

  8. Mechanically Interlocked Molecules (MIMs)-Molecular Shuttles, Switches, and Machines (Nobel Lecture).

    Science.gov (United States)

    Stoddart, J Fraser

    2017-09-04

    Chemistry welcomes a new bond: The mechanical bond has endowed molecules with component parts whose movements can be controlled and monitored. In his Nobel Lecture, J. F. Stoddart describes how being able to template the formation of mechanically interlocked molecules has led to the design and synthesis of shuttles, switches, and machines at the nanoscale. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Molecular phylogeny of the bivalve superfamily Galeommatoidea (Heterodonta, Veneroida reveals dynamic evolution of symbiotic lifestyle and interphylum host switching

    Directory of Open Access Journals (Sweden)

    Goto Ryutaro

    2012-09-01

    Full Text Available Abstract Background Galeommatoidea is a superfamily of bivalves that exhibits remarkably diverse lifestyles. Many members of this group live attached to the body surface or inside the burrows of other marine invertebrates, including crustaceans, holothurians, echinoids, cnidarians, sipunculans and echiurans. These symbiotic species exhibit high host specificity, commensal interactions with hosts, and extreme morphological and behavioral adaptations to symbiotic life. Host specialization to various animal groups has likely played an important role in the evolution and diversification of this bivalve group. However, the evolutionary pathway that led to their ecological diversity is not well understood, in part because of their reduced and/or highly modified morphologies that have confounded traditional taxonomy. This study elucidates the taxonomy of the Galeommatoidea and their evolutionary history of symbiotic lifestyle based on a molecular phylogenic analysis of 33 galeommatoidean and five putative galeommatoidean species belonging to 27 genera and three families using two nuclear ribosomal genes (18S and 28S ribosomal DNA and a nuclear (histone H3 and mitochondrial (cytochrome oxidase subunit I protein-coding genes. Results Molecular phylogeny recovered six well-supported major clades within Galeommatoidea. Symbiotic species were found in all major clades, whereas free-living species were grouped into two major clades. Species symbiotic with crustaceans, holothurians, sipunculans, and echiurans were each found in multiple major clades, suggesting that host specialization to these animal groups occurred repeatedly in Galeommatoidea. Conclusions Our results suggest that the evolutionary history of host association in Galeommatoidea has been remarkably dynamic, involving frequent host switches between different animal phyla. Such an unusual pattern of dynamic host switching is considered to have resulted from their commensalistic lifestyle, in

  10. GPU Accelerated Discrete Element Method (DEM) Molecular Dynamics for Conservative, Faceted Particle Simulations

    CERN Document Server

    Spellings, Matthew; Anderson, Joshua A; Glotzer, Sharon C

    2016-01-01

    Faceted shapes, such as polyhedra, are commonly found in systems of nanoscale, colloidal, and granular particles. Many interesting physical phenomena, like crystal nucleation and growth, vacancy motion, and glassy dynamics are challenging to model in these systems because they require detailed dynamical information at the individual particle level. Within the granular materials community the Discrete Element Method has been used extensively to model systems of anisotropic particles under gravity, with friction. We provide an implementation of this method intended for simulation of hard, faceted nanoparticles, with a conservative Weeks-Chandler-Andersen (WCA) interparticle potential, coupled to a thermodynamic ensemble. This method is a natural extension of classical molecular dynamics and enables rigorous thermodynamic calculations for faceted particles.

  11. GPU accelerated Discrete Element Method (DEM) molecular dynamics for conservative, faceted particle simulations

    Science.gov (United States)

    Spellings, Matthew; Marson, Ryan L.; Anderson, Joshua A.; Glotzer, Sharon C.

    2017-04-01

    Faceted shapes, such as polyhedra, are commonly found in systems of nanoscale, colloidal, and granular particles. Many interesting physical phenomena, like crystal nucleation and growth, vacancy motion, and glassy dynamics are challenging to model in these systems because they require detailed dynamical information at the individual particle level. Within the granular materials community the Discrete Element Method has been used extensively to model systems of anisotropic particles under gravity, with friction. We provide an implementation of this method intended for simulation of hard, faceted nanoparticles, with a conservative Weeks-Chandler-Andersen (WCA) interparticle potential, coupled to a thermodynamic ensemble. This method is a natural extension of classical molecular dynamics and enables rigorous thermodynamic calculations for faceted particles.

  12. GPU accelerated Discrete Element Method (DEM) molecular dynamics for conservative, faceted particle simulations

    Energy Technology Data Exchange (ETDEWEB)

    Spellings, Matthew [Chemical Engineering, University of Michigan, 2800 Plymouth Rd., Ann Arbor, MI 48109 (United States); Biointerfaces Institute, University of Michigan, 2800 Plymouth Rd., Ann Arbor, MI 48109 (United States); Marson, Ryan L. [Materials Science & Engineering, University of Michigan, 2300 Hayward St., Ann Arbor, MI 48109 (United States); Biointerfaces Institute, University of Michigan, 2800 Plymouth Rd., Ann Arbor, MI 48109 (United States); Anderson, Joshua A. [Chemical Engineering, University of Michigan, 2800 Plymouth Rd., Ann Arbor, MI 48109 (United States); Biointerfaces Institute, University of Michigan, 2800 Plymouth Rd., Ann Arbor, MI 48109 (United States); Glotzer, Sharon C., E-mail: sglotzer@umich.edu [Chemical Engineering, University of Michigan, 2800 Plymouth Rd., Ann Arbor, MI 48109 (United States); Materials Science & Engineering, University of Michigan, 2300 Hayward St., Ann Arbor, MI 48109 (United States); Biointerfaces Institute, University of Michigan, 2800 Plymouth Rd., Ann Arbor, MI 48109 (United States)

    2017-04-01

    Faceted shapes, such as polyhedra, are commonly found in systems of nanoscale, colloidal, and granular particles. Many interesting physical phenomena, like crystal nucleation and growth, vacancy motion, and glassy dynamics are challenging to model in these systems because they require detailed dynamical information at the individual particle level. Within the granular materials community the Discrete Element Method has been used extensively to model systems of anisotropic particles under gravity, with friction. We provide an implementation of this method intended for simulation of hard, faceted nanoparticles, with a conservative Weeks–Chandler–Andersen (WCA) interparticle potential, coupled to a thermodynamic ensemble. This method is a natural extension of classical molecular dynamics and enables rigorous thermodynamic calculations for faceted particles.

  13. Conserved water molecules in family 1 glycosidases: a DXMS and molecular dynamics study.

    Science.gov (United States)

    Teze, David; Hendrickx, Johann; Dion, Michel; Tellier, Charles; Woods, Virgil L; Tran, Vinh; Sanejouand, Yves-Henri

    2013-08-27

    By taking advantage of the wealth of structural data available for family 1 glycoside hydrolases, a study of the conservation of internal water molecules found in this ubiquitous family of enzymes was undertaken. Strikingly, seven water molecules are observed in more than 90% of the known structures. To gain insight into their possible function, the water dynamics inside Thermus thermophilus β-glycosidase was probed using deuterium exchange mass spectroscopy, allowing the pinpointing of peptide L117-A125, which exchanges most of its amide hydrogens quickly in spite of the fact that it is for the most part buried in the crystal structure. To help interpret this result, a molecular dynamics simulation was performed whose analysis suggests that two water channels are involved in the process. The longest one (∼16 Å) extends between the protein surface and W120, whose side chain interacts with E164 (the acid-base residue involved in the catalytic mechanism), whereas the other channel allows for the exchange with the bulk of the highly conserved water molecules belonging to the hydration shell of D121, a deeply buried residue. Our simulation also shows that another chain of highly conserved water molecules, going from the protein surface to the bottom of the active site cleft close to the nucleophile residue involved in the catalytic mechanism, is able to exchange with the bulk on the nanosecond time scale. It is tempting to speculate that at least one of these three water channels could be involved in the function of family 1 glycoside hydrolases.

  14. pH-responsive self-duplex of (Py)A-substituted oligodeoxyadenylate in graphene oxide solution as a molecular switch.

    Science.gov (United States)

    Yi, Jeong Wu; Park, Jaesung; Kim, Kwang S; Kim, Byeang Hyean

    2011-11-07

    In this paper, we demonstrated a highly discriminated and reliable molecular switch based on the interaction between the self-duplex of (Py)A-substituted oligodeoxyadenylate and graphene oxide in aqueous solution. This system showed a clear on/off state through the association and dissociation of (Py)A-modified oligodeoxynucleotide with graphene oxide in manipulated pH conditions, high amplitude efficiency for at least 50 cycles, and rapid response within seconds. Our molecular switch system has high reproducibility and simple operation by using pH stimulus.

  15. Sialic Acid-Responsive Polymeric Interface Material: From Molecular Recognition to Macroscopic Property Switching

    Science.gov (United States)

    Xiong, Yuting; Jiang, Ge; Li, Minmin; Qing, Guangyan; Li, Xiuling; Liang, Xinmiao; Sun, Taolei

    2017-01-01

    Biological systems that utilize multiple weak non-covalent interactions and hierarchical assemblies to achieve various bio-functions bring much inspiration for the design of artificial biomaterials. However, it remains a big challenge to correlate underlying biomolecule interactions with macroscopic level of materials, for example, recognizing such weak interaction, further transforming it into regulating material’s macroscopic property and contributing to some new bio-applications. Here we designed a novel smart polymer based on polyacrylamide (PAM) grafted with lactose units (PAM-g-lactose0.11), and reported carbohydrate-carbohydrate interaction (CCI)-promoted macroscopic properties switching on this smart polymer surface. Detailed investigations indicated that the binding of sialic acid molecules with the grafted lactose units via the CCIs induced conformational transformation of the polymer chains, further resulted in remarkable and reversible switching in surface topography, wettability and stiffness. With these excellent recognition and response capacities towards sialic acid, the PAM-g-lactose0.11 further facilitated good selectivity, strong anti-interference and high adsorption capacity in the capture of sialylated glycopeptides (important biomarkers for cancers). This work provides some enlightenment for the development of biointerface materials with tunable property, as well as high-performance glycopeptide enrichment materials. PMID:28084463

  16. Sialic Acid-Responsive Polymeric Interface Material: From Molecular Recognition to Macroscopic Property Switching

    Science.gov (United States)

    Xiong, Yuting; Jiang, Ge; Li, Minmin; Qing, Guangyan; Li, Xiuling; Liang, Xinmiao; Sun, Taolei

    2017-01-01

    Biological systems that utilize multiple weak non-covalent interactions and hierarchical assemblies to achieve various bio-functions bring much inspiration for the design of artificial biomaterials. However, it remains a big challenge to correlate underlying biomolecule interactions with macroscopic level of materials, for example, recognizing such weak interaction, further transforming it into regulating material’s macroscopic property and contributing to some new bio-applications. Here we designed a novel smart polymer based on polyacrylamide (PAM) grafted with lactose units (PAM-g-lactose0.11), and reported carbohydrate-carbohydrate interaction (CCI)-promoted macroscopic properties switching on this smart polymer surface. Detailed investigations indicated that the binding of sialic acid molecules with the grafted lactose units via the CCIs induced conformational transformation of the polymer chains, further resulted in remarkable and reversible switching in surface topography, wettability and stiffness. With these excellent recognition and response capacities towards sialic acid, the PAM-g-lactose0.11 further facilitated good selectivity, strong anti-interference and high adsorption capacity in the capture of sialylated glycopeptides (important biomarkers for cancers). This work provides some enlightenment for the development of biointerface materials with tunable property, as well as high-performance glycopeptide enrichment materials.

  17. A solid-state electrochemiluminescence biosensing switch for detection of DNA hybridization based on ferrocene-labeled molecular beacon

    Energy Technology Data Exchange (ETDEWEB)

    Wang Xiaoying [School of Public Health, Southeast University, Nanjing 210009 (China); He Pingang, E-mail: pghe@chem.ecnu.edu.c [Department of Chemistry, East China Normal University, Shanghai 200062 (China); Fang Yuzhi, E-mail: yzfang@chem.ecnu.edu.c [Department of Chemistry, East China Normal University, Shanghai 200062 (China)

    2010-08-15

    A solid-state electrochemiluminescence (ECL) biosensing switch incorporating quenching of ECL of ruthenium(II) tris-(bipyridine) (Ru(bpy){sub 3}{sup 2+}) by ferrocene (Fc) has been successfully developed for DNA hybridization detection. The important issue for this biosensing system is based on the ferrocene-labeled molecular beacon (Fc-MB), i.e. using the special Fc-MB to react with the target DNA and then change its structure, resulting in an ECL intensity change. Under the optimal conditions, the difference of ECL intensity before and after the hybridization reaction ({Delta}I{sub ECL}) was linearly related to the concentration of the complementary sequence in the range of 10 fM-10 pM and the detection limit was down to 1.0 fM.

  18. Adaptive multi-stage integrators for optimal energy conservation in molecular simulations

    CERN Document Server

    Fernández-Pendás, Mario; Sanz-Serna, J M

    2015-01-01

    We introduce a new Adaptive Integration Approach (AIA) to be used in a wide range of molecular simulations. Given a simulation problem and a step size, the method automatically chooses the optimal scheme out of an available family of numerical integrators. Although we focus on two-stage splitting integrators, the idea may be used with more general families. In each instance, the system-specific integrating scheme identified by our approach is optimal in the sense that it provides the best conservation of energy for harmonic forces. The AIA method has been implemented in the BCAM-modified GROMACS software package. Numerical tests in molecular dynamics and hybrid Monte Carlo simulations of constrained and unconstrained physical systems show that the method successfully realises the fail-safe strategy. In all experiments, and for each of the criteria employed, the AIA is at least as good as, and often significantly outperforms the standard Verlet scheme, as well as fixed parameter, optimized two-stage integrator...

  19. Adaptive multi-stage integrators for optimal energy conservation in molecular simulations

    Science.gov (United States)

    Fernández-Pendás, Mario; Akhmatskaya, Elena; Sanz-Serna, J. M.

    2016-12-01

    We introduce a new Adaptive Integration Approach (AIA) to be used in a wide range of molecular simulations. Given a simulation problem and a step size, the method automatically chooses the optimal scheme out of an available family of numerical integrators. Although we focus on two-stage splitting integrators, the idea may be used with more general families. In each instance, the system-specific integrating scheme identified by our approach is optimal in the sense that it provides the best conservation of energy for harmonic forces. The AIA method has been implemented in the BCAM-modified GROMACS software package. Numerical tests in molecular dynamics and hybrid Monte Carlo simulations of constrained and unconstrained physical systems show that the method successfully realizes the fail-safe strategy. In all experiments, and for each of the criteria employed, the AIA is at least as good as, and often significantly outperforms the standard Verlet scheme, as well as fixed parameter, optimized two-stage integrators. In particular, for the systems where harmonic forces play an important role, the sampling efficiency found in simulations using the AIA is up to 5 times better than the one achieved with other tested schemes.

  20. Dual origin of defect magnetism in graphene and its reversible switching by molecular doping.

    Science.gov (United States)

    Nair, R R; Tsai, I-L; Sepioni, M; Lehtinen, O; Keinonen, J; Krasheninnikov, A V; Castro Neto, A H; Katsnelson, M I; Geim, A K; Grigorieva, I V

    2013-01-01

    Control of magnetism by applied voltage is desirable for spintronics applications. Finding a suitable material remains an elusive goal, with only a few candidates found so far. Graphene is one of them and attracts interest because of its weak spin-orbit interaction, the ability to control electronic properties by the electric field effect and the possibility to introduce paramagnetic centres such as vacancies and adatoms. Here we show that the magnetism of adatoms in graphene is itinerant and can be controlled by doping, so that magnetic moments are switched on and off. The much-discussed vacancy magnetism is found to have a dual origin, with two approximately equal contributions; one from itinerant magnetism and the other from dangling bonds. Our work suggests that graphene's spin transport can be controlled by the field effect, similar to its electronic and optical properties, and that spin diffusion can be significantly enhanced above a certain carrier density.

  1. Functional Proteomics Defines the Molecular Switch Underlying FGF Receptor Trafficking and Cellular Outputs

    DEFF Research Database (Denmark)

    Francavilla, Chiara; Rigbolt, Kristoffer T.G.; Emdal, Kristina B

    2013-01-01

    The stimulation of fibroblast growth factor receptors (FGFRs) with distinct FGF ligands generates specific cellular responses. However, the mechanisms underlying this paradigm have remained elusive. Here, we show that FGF-7 stimulation leads to FGFR2b degradation and, ultimately, cell proliferation......, whereas FGF-10 promotes receptor recycling and cell migration. By combining mass-spectrometry-based quantitative proteomics with fluorescence microscopy and biochemical methods, we find that FGF-10 specifically induces the rapid phosphorylation of tyrosine (Y) 734 on FGFR2b, which leads to PI3K and SH3BP4...... recruitment. This complex is crucial for FGFR2b recycling and responses, given that FGF-10 stimulation of either FGFR2b_Y734F mutant- or SH3BP4-depleted cells switches the receptor endocytic route to degradation, resulting in decreased breast cancer cell migration and the inhibition of epithelial branching...

  2. Four- and Sixfold Tandem-Domino Reactions Leading to Dimeric Tetrasubstituted Alkenes Suitable as Molecular Switches.

    Science.gov (United States)

    Tietze, Lutz F; Waldecker, Bernd; Ganapathy, Dhandapani; Eichhorst, Christoph; Lenzer, Thomas; Oum, Kawon; Reichmann, Sven O; Stalke, Dietmar

    2015-08-24

    A highly efficient palladium-catalyzed fourfold tandem-domino reaction consisting of two carbopalladation and two C-H-activation steps was developed for the synthesis of two types of tetrasubstituted alkenes 3 and 6 with intrinsic helical chirality starting from substrates 1 and 4, respectively. A sixfold tandem-domino reaction was also developed by including a Sonogashira reaction. 20 compounds with different substitution patterns were prepared with yields of up to 97 %. Structure elucidation by X-ray crystallography confirmed helical chirality of the two alkene moieties. Photophysical investigations of some of the compounds showed pronounced switching properties through light-controlled changes of their stereochemical configuration. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. The effects of threonine phosphorylation on the stability and dynamics of the central molecular switch region of 18.5-kDa myelin basic protein.

    Directory of Open Access Journals (Sweden)

    Kenrick A Vassall

    global structure of the peptides through altered electrostatic interactions. The results support the hypothesis that the central conserved segment of MBP constitutes a molecular switch in which the conformation and/or intermolecular interactions are mediated by phosphorylation/dephosphorylation at T92 and T95.

  4. The effects of threonine phosphorylation on the stability and dynamics of the central molecular switch region of 18.5-kDa myelin basic protein.

    Science.gov (United States)

    Vassall, Kenrick A; Bessonov, Kyrylo; De Avila, Miguel; Polverini, Eugenia; Harauz, George

    2013-01-01

    of the peptides through altered electrostatic interactions. The results support the hypothesis that the central conserved segment of MBP constitutes a molecular switch in which the conformation and/or intermolecular interactions are mediated by phosphorylation/dephosphorylation at T92 and T95.

  5. Thermal modulation of the monomer/excimer fluorescence for bispyrene molecules through the gel solution transition of an organogel: A thermo-driven molecular fluorescence switch

    Science.gov (United States)

    Wang, Cheng; Wang, Zhuo; Zhang, Deqing; Zhu, Daoben

    2006-09-01

    Reversible modulation of the monomer/excimer emission was observed for bispyrene molecules 1 and 2 through the solution-gel phase transition (with gelator 3 as the LMWG) and accordingly a thermo-driven molecular fluorescence switch can be established.

  6. Molecular-Mechanical Switching at the Nanoparticle-Solvent Interface: Practice and Theory

    Energy Technology Data Exchange (ETDEWEB)

    Coskun, Ali [Northwestern Univ., Evanston, IL (United States); Wesson, Paul J. [Northwestern Univ., Evanston, IL (United States); Klajn, Rafal [Northwestern Univ., Evanston, IL (United States); Trabolsi, Ali [Northwestern Univ., Evanston, IL (United States); Fang, Lei [Northwestern Univ., Evanston, IL (United States); Olson, Mark A. [Northwestern Univ., Evanston, IL (United States); Dey, Sanjeev K. [Northwestern Univ., Evanston, IL (United States); Grzybowski, Bartosz A. [Northwestern Univ., Evanston, IL (United States); Stoddart, J. Fraser [Northwestern Univ., Evanston, IL (United States)

    2010-01-01

    A range (Au, Pt, Pd) of metal nanoparticles (MNPs) has been prepared and functionalized with (a) redox-active stalks containing tetrathiafulvalene (TTF) units, (b) [2]pseudorotaxanes formed between these stalks and cyclobis(paraquat-p-phenylene) (CBPQT4+) rings, and (c) bistable [2]rotaxane molecules where the dumbbell component contains a 1,5-dioxynaphthalene (DNP) unit, as well as a TTF unit, encircled by a CBPQT4+ ring. It transpires that the molecules present in (a) and (c) and the supermolecules described in (b) retain their switching characteristics, previously observed in solution, when they are immobilized onto MNPs. Moreover, their oxidation potentials depend on the fraction, χ, of the molecules or supermolecules on the surface of the nanoparticles. A variation in χ affects the oxidation potentials of the TTF units to the extent that switching can be subjected to fine tuning as a result. Specifically, increasing χ results in positive shifts (i) in the oxidation potentials of the TTF unit in (a)-(c) and (ii) the reduction potentials of the CBPQT4+ rings in (c). These shifts can be attributed to an increase in the electrostatic potential surrounding the MNPs. Both the magnitude and the direction of these shifts are reproduced by a model, based on the Poisson-Boltzmann equation coupled with charge-regulating boundary conditions. Furthermore, the kinetics of relaxation from the metastable state coconformation (MSCC) to the ground-state coconformation (GSCC) of the bistable [2]rotaxane molecules also depends on χ, as well as on the nanoparticle diameter. Increasing either of these parameters accelerates the rate of relaxation from the MSCC to the GSCC. This rate is a function of (i) the activation energy for the relaxation process associated with the bistable [2]rotaxane molecules in solution and (ii) the electrostatic potential surrounding the MNPs. The electrostatic potential depends on (i) the diameter of the MNPs, (ii

  7. Caveolin isoform switching as a molecular, structural, and metabolic regulator of microglia

    OpenAIRE

    2013-01-01

    Microglia are ramified cells that serve as central nervous system (CNS) guardians, capable of proliferation, migration, and generation of inflammatory cytokines. In non-pathological states, these cells exhibit ramified morphology with processes intermingling with neurons and astrocytes. Under pathological conditions, they acquire a rounded amoeboid morphology and proliferative and migratory capabilities. Such morphological changes require cytoskeleton rearrangements. The molecular control poi...

  8. Molecular Characterization and Immune Protection of a New Conserved Hypothetical Protein of Eimeria tenella.

    Directory of Open Access Journals (Sweden)

    Qi Zhai

    Full Text Available The genome sequences of Eimeria tenella have been sequenced, but >70% of these genes are currently categorized as having an unknown function or annotated as conserved hypothetical proteins, and few of them have been studied. In the present study, a conserved hypothetical protein gene of E. tenella, designated EtCHP559, was cloned using rapid amplification of cDNA 5'-ends (5'RACE based on the expressed sequence tag (EST. The 1746-bp full-length cDNA of EtCHP559 contained a 1224-bp open reading frame (ORF that encoded a 407-amino acid polypeptide with the predicted molecular weight of 46.04 kDa. Real-time quantitative PCR analysis revealed that EtCHP559 was expressed at higher levels in sporozoites than in the other developmental stages (unsporulated oocysts, sporulated oocysts and second generation merozoites. The ORF was inserted into pCold-TF to produce recombinant EtCHP559. Using western blotting, the recombinant protein was successfully recognized by rabbit serum against E. tenella sporozoites. Immunolocalization by using EtCHP559 antibody showed that EtCHP559 was mainly distributed on the parasite surface in free sporozoites and became concentrated in the anterior region after sporozoites were incubated in complete medium. The EtCHP559 became uniformly dispersed in immature and mature schizonts. Inhibition of EtCHP559 function using anti-rEtCHP559 polyclonal antibody reduced the ability of E. tenella sporozoites to invade host cells by >70%. Animal challenge experiments demonstrated that the recombinant EtCHP559 significantly increased the average body weight gain, reduced the oocyst outputs, alleviated cecal lesions of the infected chickens, and resulted in anticoccidial index >160 against E. tenella. These results suggest that EtCHP559 plays an important role in sporozoite invasion and could be an effective candidate for the development of a new vaccine against E. tenella.

  9. Structures of the NLRP14 pyrin domain reveal a conformational switch mechanism regulating its molecular interactions

    Energy Technology Data Exchange (ETDEWEB)

    Eibl, Clarissa; Hessenberger, Manuel; Wenger, Julia; Brandstetter, Hans, E-mail: hans.brandstetter@sbg.ac.at [University of Salzburg, Billrothstrasse 11, 5020 Salzburg (Austria)

    2014-07-01

    Pyrin domains (PYDs) recruit downstream effector molecules in NLR signalling. A specific charge-relay system suggests a the formation of a signalling complex involving a PYD dimer. The cytosolic tripartite NLR receptors serve as important signalling platforms in innate immunity. While the C-terminal domains act as sensor and activation modules, the N-terminal death-like domain, e.g. the CARD or pyrin domain, is thought to recruit downstream effector molecules by homotypic interactions. Such homotypic complexes have been determined for all members of the death-domain superfamily except for pyrin domains. Here, crystal structures of human NLRP14 pyrin-domain variants are reported. The wild-type protein as well as the clinical D86V mutant reveal an unexpected rearrangement of the C-terminal helix α6, resulting in an extended α5/6 stem-helix. This reordering mediates a novel symmetric pyrin-domain dimerization mode. The conformational switching is controlled by a charge-relay system with a drastic impact on protein stability. How the identified charge relay allows classification of NLRP receptors with respect to distinct recruitment mechanisms is discussed.

  10. Multi-scale coarse-graining of non-conservative interactions in molecular liquids

    Energy Technology Data Exchange (ETDEWEB)

    Izvekov, Sergei, E-mail: sergiy.izvyekov.civ@mail.mil; Rice, Betsy M. [U.S. Army Research Laboratory, Aberdeen Proving Ground, Maryland 21005 (United States)

    2014-03-14

    A new bottom-up procedure for constructing non-conservative (dissipative and stochastic) interactions for dissipative particle dynamics (DPD) models is described and applied to perform hierarchical coarse-graining of a polar molecular liquid (nitromethane). The distant-dependent radial and shear frictions in functional-free form are derived consistently with a chosen form for conservative interactions by matching two-body force-velocity and three-body velocity-velocity correlations along the microscopic trajectories of the centroids of Voronoi cells (clusters), which represent the dissipative particles within the DPD description. The Voronoi tessellation is achieved by application of the K-means clustering algorithm at regular time intervals. Consistently with a notion of many-body DPD, the conservative interactions are determined through the multi-scale coarse-graining (MS-CG) method, which naturally implements a pairwise decomposition of the microscopic free energy. A hierarchy of MS-CG/DPD models starting with one molecule per Voronoi cell and up to 64 molecules per cell is derived. The radial contribution to the friction appears to be dominant for all models. As the Voronoi cell sizes increase, the dissipative forces rapidly become confined to the first coordination shell. For Voronoi cells of two and more molecules the time dependence of the velocity autocorrelation function becomes monotonic and well reproduced by the respective MS-CG/DPD models. A comparative analysis of force and velocity correlations in the atomistic and CG ensembles indicates Markovian behavior with as low as two molecules per dissipative particle. The models with one and two molecules per Voronoi cell yield transport properties (diffusion and shear viscosity) that are in good agreement with the atomistic data. The coarser models produce slower dynamics that can be appreciably attributed to unaccounted dissipation introduced by regular Voronoi re-partitioning as well as by larger

  11. Porphyrinic metal-organic framework as electrochemical probe for DNA sensing via triple-helix molecular switch.

    Science.gov (United States)

    Ling, Pinghua; Lei, Jianping; Ju, Huangxian

    2015-09-15

    An electrochemical DNA sensor was developed based on the electrocatalysis of porphyrinic metal-organic framework (MOF) and triple-helix molecular switch for signal transduction. The streptavidin functionalized zirconium-porphyrin MOF (PCN-222@SA) was prepared as signal nanoprobe via covalent method and demonstrated high electrocatalysis for O2 reduction. Due to the large steric effect, the designed nanoprobe was blocked for the interaction with the biotin labeled triple-helix immobilized on the surface of glassy carbon electrode. In the presence of target DNA, the assistant DNA in triple-helix will hybridize with target DNA, resulting in the disassembly of triple-helix molecular. Consequently, the end biotin away from the electrode was ''activated'' for easy access to the signal nanoprobe, PCN-222@SA, on the basis of biotin-streptavidin biorecognition. The introduction of signal nanoprobe to a sensor surface led to a significantly amplified electrocatalytic current towards oxygen reduction. Integrating with DNA recycling amplification of Exonuclease III, the sensitivity of the biosensor was improved significantly with detection limit of 0.29 fM. Moreover, the present method has been successfully applied to detect DNA in complex serum matrix. This porphyrinic MOF-based strategy has promising application in the determination of various analytes for signal transduction and has great potential in bioassays.

  12. Molecular engineering of lanthanide ion chelating phospholipids generating assemblies with a switched magnetic susceptibility.

    Science.gov (United States)

    Isabettini, Stéphane; Massabni, Sarah; Hodzic, Arnel; Durovic, Dzana; Kohlbrecher, Joachim; Ishikawa, Takashi; Fischer, Peter; Windhab, Erich J; Walde, Peter; Kuster, Simon

    2017-08-09

    Lanthanide ion (Ln(3+)) chelating amphiphiles are powerful molecules for tailoring the magnetic response of polymolecular assemblies. Mixtures of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-dimyristoyl-sn-glycero-3-phospho-ethanolamine-diethylene triaminepentaacetate (DMPE-DTPA) complexed to Ln(3+) deliver highly magnetically responsive bicelles. Their magnetic properties are readily tuned by changing the bicellar size or the magnetic susceptibility Δχ of the bilayer lipids. The former technique is intrinsically bound to the region of the phase diagram guarantying the formation of bicelles. Methods aiming towards manipulating the Δχ of the bilayer are comparatively more robust, flexible and lacking. Herein, we synthesized a new Ln(3+) chelating phospholipid using glutamic acid as a backbone: DMPE-Glu-DTPA. The chelate polyhedron was specifically engineered to alter the Δχ, whilst remaining geometrically similar to DMPE-DTPA. Planar asymmetric assemblies hundreds of nanometers in size were achieved presenting unprecedented magnetic alignments. The DMPE-Glu-DTPA/Ln(3+) complex switched the Δχ, achieving perpendicular alignment of assemblies containing Dy(3+) and parallel alignment of those containing Tm(3+). Moreover, samples with chelated Yb(3+) were more alignable than the Tm(3+) chelating counterparts. Such a possibility has never been demonstrated for planar Ln(3+) chelating polymolecular assemblies. The physico-chemical properties of these novel assemblies were further studied by monitoring the alignment behavior at different temperatures and by including 16 mol% of cholesterol (Chol-OH) in the phospholipid bilayer. The DMPE-Glu-DTPA/Ln(3+) complex and the resulting assemblies are promising candidates for applications in numerous fields including pharmaceutical technologies, structural characterization of membrane biomolecules by NMR spectroscopy, as contrasting agents for magnetic resonance imaging, and for the development of smart

  13. Inducible molecular switches for the study of long-term potentiation.

    Science.gov (United States)

    Hédou, Gaël; Mansuy, Isabelle M

    2003-04-29

    This article reviews technical and conceptual advances in unravelling the molecular bases of long-term potentiation (LTP), learning and memory using genetic approaches. We focus on studies aimed at testing a model suggesting that protein kinases and protein phosphatases balance each other to control synaptic strength and plasticity. We describe how gene 'knock-out' technology was initially exploited to disrupt the Ca(2+)/calmodulin-dependent protein kinase IIalpha (CaMKIIalpha) gene and how refined knock-in techniques later allowed an analysis of the role of distinct phosphorylation sites in CaMKII. Further to gene recombination, regulated gene expression using the tetracycline-controlled transactivator and reverse tetracycline-controlled transactivator systems, a powerful new means for modulating the activity of specific molecules, has been applied to CaMKIIalpha and the opposing protein phosphatase calcineurin. Together with electro-physiological and behavioural evaluation of the engineered mutant animals, these genetic methodologies have helped gain insight into the molecular mechanisms of plasticity and memory. Further technical developments are, however, awaited for an even higher level of finesse.

  14. Conservation of the glucan phosphatase laforin is linked to rates of molecular evolution and the glucan metabolism of the organism

    Directory of Open Access Journals (Sweden)

    Pace Rachel M

    2009-06-01

    Full Text Available Abstract Background Lafora disease (LD is a fatal autosomal recessive neurodegenerative disease. A hallmark of LD is cytoplasmic accumulation of insoluble glucans, called Lafora bodies (LBs. Mutations in the gene encoding the phosphatase laforin account for ~50% of LD cases, and this gene is conserved in all vertebrates. We recently demonstrated that laforin is the founding member of a unique class of phosphatases that dephosphorylate glucans. Results Herein, we identify laforin orthologs in a protist and two invertebrate genomes, and report that laforin is absent in the vast majority of protozoan genomes and it is lacking in all other invertebrate genomes sequenced to date. We biochemically characterized recombinant proteins from the sea anemone Nematostella vectensis and the amphioxus Branchiostoma floridae to demonstrate that they are laforin orthologs. We demonstrate that the laforin gene has a unique evolutionary lineage; it is conserved in all vertebrates, a subclass of protists that metabolize insoluble glucans resembling LBs, and two invertebrates. We analyzed the intron-exon boundaries of the laforin genes in each organism and determine, based on recently published reports describing rates of molecular evolution in Branchiostoma and Nematostella, that the conservation of laforin is linked to the molecular rate of evolution and the glucan metabolism of an organism. Conclusion Our results alter the existing view of glucan phosphorylation/dephosphorylation and strongly suggest that glucan phosphorylation is a multi-Kingdom regulatory mechanism, encompassing at least some invertebrates. These results establish boundaries concerning which organisms contain laforin. Laforin is conserved in all vertebrates, it has been lost in the vast majority of lower organisms, and yet it is an ancient gene that is conserved in a subset of protists and invertebrates that have undergone slower rates of molecular evolution and/or metabolize a carbohydrate

  15. Molecular rectification and conductance switching in carbon-based molecular junctions by structural rearrangement accompanying electron injection.

    Science.gov (United States)

    McCreery, Richard; Dieringer, Jon; Solak, Ali Osman; Snyder, Brian; Nowak, Aletha M; McGovern, William R; DuVall, Stacy

    2003-09-01

    Molecular junctions were fabricated consisting of a 3.7 nm thick layer of nitroazobenzene (NAB) molecules between a pyrolyzed photoresist substrate (PPF) and a titanium top contact which was protected from oxidation by a layer of gold. Raman spectroscopy, XPS, and AFM revealed that the NAB layer was 2-3 molecules thick and was bonded to the two conducting contacts by C-C and N-Ti covalent bonds. The current/voltage behavior of the PPF/NAB(3.7)/Ti junctions showed strong and reproducible rectification, with the current at +2 V exceeding that at -2 V by a factor of 600. The observed current density at +3 V was 0.71 A/cm(2), or about 10(5) e(-)/s/molecule. The i/V response was strongly dependent on temperature and scan rate, with the rectification ratio decreasing for lower temperature and faster scans. Junction conductivity increased with time over several seconds at room temperature in response to positive voltage pulses, with the rate of increase larger for more positive potentials. Voltage pulses to positive potentials and back to zero volts revealed that electrons are injected from the Ti to the NAB, to the extent of about 0.1-1 e(-)/molecule for a +3 V pulse. These electrons cause an activated transition of the NAB into a more conductive quinoid state, which in turn causes an increase in conductivity. The transition to the quinoid state involves nuclear rearrangement which occurs on a submillisecond to several second time scale, depending on the voltage applied. The quinoid state is stable as long as the applied electric field is present, but reverts back to NAB within several minutes after the field is relaxed. The results are interpreted in terms of a thermally activated, potential dependent electron transfer into the 3.7 nm NAB layer, which brings about a conductivity increase of several orders of magnitude.

  16. Structural basis of syndecan-4 phosphorylation as a molecular switch to regulate signaling

    DEFF Research Database (Denmark)

    Koo, Bon-Kyung; Jung, Young Sang; Shin, Joon

    2005-01-01

    The syndecan transmembrane proteoglycans are involved in the organization of the actin cytoskeleton and have important roles as cell surface receptors during cell-matrix interactions. We have shown that the syndecan-4 cytoplasmic domain (4L) forms oligomeric complexes that bind to and stimulate...... PKCalpha activity in the presence of PtdIns(4,5)P2, emphasizing the importance of multimerization in the regulation of PKCalpha activation. Oligomerization of the cytoplasmic domain of syndecan-4 is regulated either positively by PtdIns(4,5)P2 or negatively by phosphorylation of serine 183. Phosphorylation...... analysis showed that the overall conformation of p-4L is a compact intertwined dimer with an unusually symmetric clamp shape, and its molecular surface is mostly positively charged. The two parallel strands form a cavity in the center of the dimeric twist. An especially marked effect of phosphorylation...

  17. Laser control of double proton transfer in porphycenes. Towards an ultrafast switch for photonic molecular wires

    CERN Document Server

    Abdel-Latif, Mahmoud K

    2010-01-01

    Electronic excitation energy transfer along a molecular wire depends on the relative orientation of the electronic transition dipole moments of neighboring chromophores. In porphycenes this orientation is changed upon double proton transfer in the electronic ground state. We explore the possibility to trigger such a double proton transfer reaction by means of an infrared pump-dump laser control scheme. To this end a quantum chemical characterization of an asymmetrically substituted porphycene is performed using density functional theory. Ground state geometries, the topology of the potential energy surface for double proton transfer, and S0->S1 transition energies are compared with the parent compound porphycene and a symmetric derivative. Employing a simple two-dimensional model for the double proton transfer, which incorporates sequential and concerted motions, quantum dynamics simulations of the laser driven dynamics are performed which demonstrate tautomerization control. Based on the orientation of the t...

  18. Plasma membranes as heat stress sensors: from lipid-controlled molecular switches to therapeutic applications.

    Science.gov (United States)

    Török, Zsolt; Crul, Tim; Maresca, Bruno; Schütz, Gerhard J; Viana, Felix; Dindia, Laura; Piotto, Stefano; Brameshuber, Mario; Balogh, Gábor; Péter, Mária; Porta, Amalia; Trapani, Alfonso; Gombos, Imre; Glatz, Attila; Gungor, Burcin; Peksel, Begüm; Vigh, László; Csoboz, Bálint; Horváth, Ibolya; Vijayan, Mathilakath M; Hooper, Phillip L; Harwood, John L; Vigh, László

    2014-06-01

    The classic heat shock (stress) response (HSR) was originally attributed to protein denaturation. However, heat shock protein (Hsp) induction occurs in many circumstances where no protein denaturation is observed. Recently considerable evidence has been accumulated to the favor of the "Membrane Sensor Hypothesis" which predicts that the level of Hsps can be changed as a result of alterations to the plasma membrane. This is especially pertinent to mild heat shock, such as occurs in fever. In this condition the sensitivity of many transient receptor potential (TRP) channels is particularly notable. Small temperature stresses can modulate TRP gating significantly and this is influenced by lipids. In addition, stress hormones often modify plasma membrane structure and function and thus initiate a cascade of events, which may affect HSR. The major transactivator heat shock factor-1 integrates the signals originating from the plasma membrane and orchestrates the expression of individual heat shock genes. We describe how these observations can be tested at the molecular level, for example, with the use of membrane perturbers and through computational calculations. An important fact which now starts to be addressed is that membranes are not homogeneous nor do all cells react identically. Lipidomics and cell profiling are beginning to address the above two points. Finally, we observe that a deregulated HSR is found in a large number of important diseases where more detailed knowledge of the molecular mechanisms involved may offer timely opportunities for clinical interventions and new, innovative drug treatments. This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy.

  19. Molecular mechanism of R-bicalutamide switching from androgen receptor antagonist to agonist induced by amino acid mutations using molecular dynamics simulations and free energy calculation

    Science.gov (United States)

    Liu, Hongli; Han, Rui; Li, Jiazhong; Liu, Huanxiang; Zheng, Lifang

    2016-12-01

    R-bicalutamide, a first generation antiandrogen, was used to treat prostate cancer for decades. Although it is very effective at the beginning, resistance appears after 2-3 years of treatment. Mutation of androgen receptor (AR) is considered a main reason for drug resistance. It is reported that AR W741C, W741L, W741C_T877A, T877A, F876L, F876L_T877A and L701H mutations can convert R-bicalutamide from AR antagonist to agonist, but the switching mechanisms are not clear. In this study, molecular dynamics simulations and molecular mechanics generalized Born surface area (MM-GBSA) calculations were performed to analyze the interaction mechanisms between R-bicalutamide and wild type/mutant ARs. The results indicate that helix H12, which lies on the top of AR LBD like a cover, plays a vital role in R-bicalutamide binding. When interacting with AR, the B-ring of R-bicalutamide pushes H12 aside, distorting the coactivator binding site (AF2) resulting in the inactivation of transcription. Several residue mutations appear to enlarge the distance between the B-ring of R-bicalutamide and H12, reducing steric clash, which is conducive to a closed H12 conformation, leading to the formation of the coactivator binding site AF2 and increased transcription. Hydrogen bond and per-residue free energy decomposition analyses are also investigated to explore the interacting mechanisms, and M895 is found to be a key residue in the antagonist mechanism. The obtained molecular mechanisms will aid rational screening and design of novel AR antagonists, even to mutant AR.

  20. Chromosomal islands of Streptococcus pyogenes and related streptococci: molecular switches for survival and virulence.

    Science.gov (United States)

    Nguyen, Scott V; McShan, William M

    2014-01-01

    Streptococcus pyogenes is a significant pathogen of humans, annually causing over 700,000,000 infections and 500,000 deaths. Virulence in S. pyogenes is closely linked to mobile genetic elements like phages and chromosomal islands (CI). S. pyogenes phage-like chromosomal islands (SpyCI) confer a complex mutator phenotype on their host. SpyCI integrate into the 5' end of DNA mismatch repair (MMR) gene mutL, which also disrupts downstream operon genes lmrP, ruvA, and tag. During early logarithmic growth, SpyCI excise from the bacterial chromosome and replicate as episomes, relieving the mutator phenotype. As growth slows and the cells enter stationary phase, SpyCI reintegrate into the chromosome, again silencing the MMR operon. This system creates a unique growth-dependent and reversible mutator phenotype. Additional CI using the identical attachment site in mutL have been identified in related species, including Streptococcus dysgalactiae subsp. equisimilis, Streptococcus anginosus, Streptococcus intermedius, Streptococcus parauberis, and Streptococcus canis. These CI have small genomes, which range from 13 to 20 kB, conserved integrase and DNA replication genes, and no identifiable genes encoding capsid proteins. SpyCI may employ a helper phage for packaging and dissemination in a fashion similar to the Staphylococcus aureus pathogenicity islands (SaPI). Outside of the core replication and integration genes, SpyCI and related CI show considerable diversity with the presence of many indels that may contribute to the host cell phenotype or fitness. SpyCI are a subset of a larger family of streptococcal CI who potentially regulate the expression of other host genes. The biological and phylogenetic analysis of streptococcal chromosomal islands provides important clues as to how these chromosomal islands help S. pyogenes and other streptococcal species persist in human populations in spite of antibiotic therapy and immune challenges.

  1. Identification of the molecular switch that regulates access of 5alpha-DHT to the androgen receptor.

    Science.gov (United States)

    Penning, Trevor M; Bauman, David R; Jin, Yi; Rizner, Tea Lanisik

    2007-02-01

    Pairs of hydroxysteroid dehydrogenases (HSDs) govern ligand access to steroid receptors in target tissues and act as molecular switches. By acting as reductases or oxidases, HSDs convert potent ligands into their cognate inactive metabolites or vice versa. This pre-receptor regulation of steroid hormone action may have profound effects on hormonal response. We have identified the HSDs responsible for regulating ligand access to the androgen receptor (AR) in human prostate. Type 3 3alpha-hydroxysteroid dehydrogenase (aldo-keto reductase 1C2) acts solely as a reductase to convert 5alpha-dihydrotestosterone (DHT), a potent ligand for the AR (K(d)=10(-11)M for the AR), to the inactive androgen 3alpha-androstanediol (K(d)=10(-6)M for the AR); while RoDH like 3alpha-HSD (a short-chain dehydrogenase/reductase (SDR)) acts solely as an oxidase to convert 3alpha-androstanediol back to 5alpha-DHT. Our studies suggest that aldo-keto reductase (AKRs) and SDRs function as reductases and oxidases, respectively, to control ligand access to nuclear receptors.

  2. Assessing computationally efficient isomerization dynamics: Delta-SCF density-functional theory study of azobenzene molecular switching

    CERN Document Server

    Maurer, Reinhard J; 10.1063/1.3664305

    2012-01-01

    We present a detailed comparison of the S0, S1 (n -> \\pi*) and S2 (\\pi -> \\pi*) potential energy surfaces (PESs) of the prototypical molecular switch azobenzene as obtained by Delta-self-consistent-field (Delta-SCF) Density-Functional Theory (DFT), time-dependent DFT (TD-DFT) and approximate Coupled Cluster Singles and Doubles (RI-CC2). All three methods unanimously agree in terms of the PES topologies, which are furthermore fully consistent with existing experimental data concerning the photo-isomerization mechanism. In particular, sum-method corrected Delta-SCF and TD-DFT yield very similar results for S1 and S2, when based on the same ground-state exchange-correlation (xc) functional. While these techniques yield the correct PES topology already on the level of semi-local xc functionals, reliable absolute excitation energies as compared to RI-CC2 or experiment require an xc treatment on the level of long-range corrected hybrids. Nevertheless, particularly the robustness of Delta-SCF with respect to state c...

  3. A sensitive and versatile "signal-on" electrochemical aptasensor based on a triple-helix molecular switch.

    Science.gov (United States)

    Wang, Xiuzhong; Jiang, Aiwen; Hou, Ting; Li, Feng

    2014-12-07

    In the present study, a versatile "signal-on" electrochemical aptasensor based on a triple-helix molecular switch has been developed. An aptamer probe is designed to hybridize with the methylene blue (MB)-modified DNA capture probe immobilized on the gold electrode to form rigid triple-helix DNA, impeding the efficient electron transfer of MB to the electrode and resulting in the decreased oxidation peak current of MB. However, upon introduction of the perfectly matched target, for example, human α-thrombin (Tmb), the interaction between Tmb and the aptamer probe leads to the dissociation of the triple-helix DNA structure and thereby liberates the MB-modified end of the capture probe, allowing the MB to collide with the electrode surface and resulting in an increase of the oxidation peak currents of MB. Therefore, the sensitive signal-on detection of Tmb is realized, and the detection limit of Tmb is 0.12 nM. The proposed approach also demonstrates excellent regenerability, reproducibility and stability. Additionally, it also has the advantages of simplicity in design and easy operation. The success in the present biosensor provides a promising alternative to the electrochemical detection of a variety of analytes and may have potential applications in point-of-care testing and clinical diagnosis.

  4. Advanced computational biology methods identify molecular switches for malignancy in an EGF mouse model of liver cancer.

    Directory of Open Access Journals (Sweden)

    Philip Stegmaier

    Full Text Available The molecular causes by which the epidermal growth factor receptor tyrosine kinase induces malignant transformation are largely unknown. To better understand EGFs' transforming capacity whole genome scans were applied to a transgenic mouse model of liver cancer and subjected to advanced methods of computational analysis to construct de novo gene regulatory networks based on a combination of sequence analysis and entrained graph-topological algorithms. Here we identified transcription factors, processes, key nodes and molecules to connect as yet unknown interacting partners at the level of protein-DNA interaction. Many of those could be confirmed by electromobility band shift assay at recognition sites of gene specific promoters and by western blotting of nuclear proteins. A novel cellular regulatory circuitry could therefore be proposed that connects cell cycle regulated genes with components of the EGF signaling pathway. Promoter analysis of differentially expressed genes suggested the majority of regulated transcription factors to display specificity to either the pre-tumor or the tumor state. Subsequent search for signal transduction key nodes upstream of the identified transcription factors and their targets suggested the insulin-like growth factor pathway to render the tumor cells independent of EGF receptor activity. Notably, expression of IGF2 in addition to many components of this pathway was highly upregulated in tumors. Together, we propose a switch in autocrine signaling to foster tumor growth that was initially triggered by EGF and demonstrate the knowledge gain form promoter analysis combined with upstream key node identification.

  5. The TOMM machinery is a molecular switch in PINK1 and PARK2/PARKIN-dependent mitochondrial clearance.

    Science.gov (United States)

    Bertolin, Giulia; Ferrando-Miguel, Rosa; Jacoupy, Maxime; Traver, Sabine; Grenier, Karl; Greene, Andrew W; Dauphin, Aurélien; Waharte, François; Bayot, Aurélien; Salamero, Jean; Lombès, Anne; Bulteau, Anne-Laure; Fon, Edward A; Brice, Alexis; Corti, Olga

    2013-11-01

    Loss-of-function mutations in PARK2/PARKIN and PINK1 cause early-onset autosomal recessive Parkinson disease (PD). The cytosolic E3 ubiquitin-protein ligase PARK2 cooperates with the mitochondrial kinase PINK1 to maintain mitochondrial quality. A loss of mitochondrial transmembrane potential (ΔΨ) leads to the PINK1-dependent recruitment of PARK2 to the outer mitochondrial membrane (OMM), followed by the ubiquitination and proteasome-dependent degradation of OMM proteins, and by the autophagy-dependent clearance of mitochondrial remnants. We showed here that blockade of mitochondrial protein import triggers the recruitment of PARK2, by PINK1, to the TOMM machinery. PD-causing PARK2 mutations weakened or disrupted the molecular interaction between PARK2 and specific TOMM subunits: the surface receptor, TOMM70A, and the channel protein, TOMM40. The downregulation of TOMM40 or its associated core subunit, TOMM22, was sufficient to trigger OMM protein clearance in the absence of PINK1 or PARK2. However, PARK2 was required to promote the degradation of whole organelles by autophagy. Furthermore, the overproduction of TOMM22 or TOMM40 reversed mitochondrial clearance promoted by PINK1 and PARK2 after ΔΨ loss. These results indicated that the TOMM machinery is a key molecular switch in the mitochondrial clearance program controlled by the PINK1-PARK2 pathway. Loss of functional coupling between mitochondrial protein import and the neuroprotective degradation of dysfunctional mitochondria may therefore be a primary pathogenic mechanism in autosomal recessive PD.

  6. "Molecular Switches" on mGluR Allosteric Ligands That Modulate Modes of Pharmacology

    Science.gov (United States)

    Wood, Michael R.; Hopkins, Corey R.; Brogan, John T.; Conn, P. Jeffrey; Lindsley, Craig W.

    2013-01-01

    G-Protein-coupled receptors (GPCRs) represent the largest class of drug targets, accounting for more than 40% of marketed drugs; however, discovery efforts for many GPCRs have failed to provide viable drug candidates. Historically, drug discovery efforts have focused on developing ligands that act at the orthosteric site of the endogenous agonist. Recently, efforts have focused on functional assay paradigms and the discovery of ligands that act at allosteric sites to modulate receptor function in either a positive, negative, or neutral manner. Allosteric modulators have numerous advantages over orthosteric ligands, including high subtype selectivity; the ability to mimic physiological conditions; the lack of densensitization, downregulation, and internalization; and reduced side effects. Despite these virtues, challenging issues have now arisen for allosteric modulators of metabotropic glutamate receptors (mGluRs): shallow SAR, ligand-directed trafficking, and the identification of subtle “molecular switches” that modulate the modes of pharmacology. Here, we will discuss the impact of modest structural changes to multiple mGluR allosteric ligands scaffolds that unexpectedly modulate pharmacology and raise concerns over metabolism and the pharmacology of metabolites. PMID:21341760

  7. Multi-ion detection and molecular switching behaviour of reversible dual fluorescent sensor

    Science.gov (United States)

    Basheer, Sabeel M.; Muralisankar, M.; Anjana, T. V.; Aneesrahman, K. N.; Sreekanth, Anandaram

    2017-07-01

    The selective chemosensing behaviour of imidazole bisthiocarbohydrazone (IBTC) towards F- and Cu2 + are studied via colorimetric, UV-Visible, fluorescence spectra studies, and binding constants were calculated. The 1H NMR titration study strongly support that the deprotonation of IBTC followed by the hydrogen bond formation via N1sbnd H1 and N2sbnd H2 protons with fluoride ion. The fluorescence inactive IBTC-Cu complex became fluorescence active in the presence of perchlorate (ClO4-) ion. The selective detection of perchlorate ion was also explained. The F- sensing mechanism of IBTC has been investigated by Density Functional Theory (DFT) and Time-Dependent Density Functional Theory (TDDFT) methods. The theoretical outcomes well reproduce the experimental results. And it concluded the Nsbnd H protons, nearby the imine group was first captured by the added F- ion and then deprotonation happened followed by the formation of hydrogen bond. The IBTC found good reversibility character with the alternative addition of Ca2 + and F-. The multi-ion detection of IBTC was used to construct the NOR, OR and INHIBITION molecular logic gates.

  8. Nitration of TRPM2 as a Molecular Switch Induces Autophagy During Brain Pericyte Injury.

    Science.gov (United States)

    Jiang, Quan; Gao, Yinping; Wang, Chengkun; Tao, Rongrong; Wu, Yan; Zhan, Kaiyu; Liao, Meihua; Lu, Nannan; Lu, Yingmei; Wilcox, Christopher S; Luo, Jianhong; Jiang, Lin-Hua; Yang, Wei; Han, Feng

    2017-04-18

    Dysfunction of neurovascular pericytes underlies breakdown of the blood-brain barrier, but the molecular mechanisms are largely unknown. In this study, we evaluated the role of the transient receptor potential melastatin-related 2 (TRPM2) channel and autophagy during brain pericyte injury both in vitro and in vivo. A rapid induction in autophagy in human brain vascular pericytes, in the zinc oxide nanoparticles (ZnO-NP)-induced cell stress model, was paralleled with an increase in the expression of the TRPM2-S truncated isoform, which was abolished by treatment with a nitric oxide synthase inhibitor and a peroxynitrite scavenger. Furthermore, Y1485 in the C-terminus of the TRPM2 protein was identified as the tyrosine nitration substrate by mass spectrometry. Overexpression of the Y1485S TRPM2 mutant reduced LC3-II accumulation and pericyte injury induced by ZnO-NP. Consistently, LC3-II accumulation was reduced and pericytes were better preserved in intact brain microvessels of the TRPM2 knockout mice after ZnO-NP-induced vascular injury. Innovation and Conclusions: Our present study has revealed a novel mechanism of autophagy disturbance secondary to nitrosative stress-induced tyrosine nitration of TRPM2 during pericyte injury. Antioxid. Redox Signal. 00, 000-000.

  9. Detailed Photoisomerization Dynamics of a Green Fluorescent Protein Chromophore Based Molecular Switch

    Directory of Open Access Journals (Sweden)

    Chen-Wei Jiang

    2014-01-01

    Full Text Available With density-functional-based nonadiabatic molecular dynamics simulations, trans-to-cis and cis-to-trans photoisomerizations of a green fluorescent protein chromophore based molecule 4-benzylidene-2-methyloxazol-5(4H-one (BMH induced by the excitation to its S1 excited state were performed. We find a quantum yield of 32% for the trans-to-cis photoisomerization of BMH and a quantum yield of 33% for its cis-to-trans photoisomerization. For those simulations that did produce trans-to-cis isomerization, the average S1 excited state lifetime of trans-BMH is about 1460 fs, which is much shorter than that of cis-BMH (3100 fs in those simulations that did produce cis-to-trans isomerization. For both photoisomerization processes, rotation around the central C2=C3 bond is the dominant reaction mechanism. Deexcitation occurs at an avoided crossing near the S1/S0 conical intersection, which is near the midpoint of the rotation.

  10. New Molecular Knowledge Towards the Trigemino-Cardiac Reflex as a Cerebral Oxygen-Conserving Reflex

    Directory of Open Access Journals (Sweden)

    N. Sandu

    2010-01-01

    Full Text Available The trigemino-cardiac reflex (TCR represents the most powerful of the autonomous reflexes and is a subphenomenon in the group of the so-called “oxygen-conserving reflexes”. Within seconds after the initiation of such a reflex, there is a powerful and differentiated activation of the sympathetic system with subsequent elevation in regional cerebral blood flow (CBF, with no changes in the cerebral metabolic rate of oxygen (CMRO2 or in the cerebral metabolic rate of glucose (CMRglc. Such an increase in regional CBF without a change of CMRO2 or CMRglc provides the brain with oxygen rapidly and efficiently. Features of the reflex have been discovered during skull base surgery, mediating reflex protection projects via currently undefined pathways from the rostral ventrolateral medulla oblongata to the upper brainstem and/or thalamus, which finally engage a small population of neurons in the cortex. This cortical center appears to be dedicated to transduce a neuronal signal reflexively into cerebral vasodilatation and synchronization of electrocortical activity; a fact that seems to be unique among autonomous reflexes. Sympathetic excitation is mediated by cortical-spinal projection to spinal preganglionic sympathetic neurons, whereas bradycardia is mediated via projections to cardiovagal motor medullary neurons. The integrated reflex response serves to redistribute blood from viscera to the brain in response to a challenge to cerebral metabolism, but seems also to initiate a preconditioning mechanism. Previous studies showed a great variability in the human TCR response, in special to external stimuli and individual factors. The TCR gives, therefore, not only new insights into novel therapeutic options for a range of disorders characterized by neuronal death, but also into the cortical and molecular organization of the brain.

  11. New molecular knowledge towards the trigemino-cardiac reflex as a cerebral oxygen-conserving reflex.

    Science.gov (United States)

    Sandu, N; Spiriev, T; Lemaitre, F; Filis, A; Schaller, B

    2010-05-04

    The trigemino-cardiac reflex (TCR) represents the most powerful of the autonomous reflexes and is a subphenomenon in the group of the so-called "oxygen-conserving reflexes". Within seconds after the initiation of such a reflex, there is a powerful and differentiated activation of the sympathetic system with subsequent elevation in regional cerebral blood flow (CBF), with no changes in the cerebral metabolic rate of oxygen (CMRO2) or in the cerebral metabolic rate of glucose (CMRglc). Such an increase in regional CBF without a change of CMRO2 or CMRglc provides the brain with oxygen rapidly and efficiently. Features of the reflex have been discovered during skull base surgery, mediating reflex protection projects via currently undefined pathways from the rostral ventrolateral medulla oblongata to the upper brainstem and/or thalamus, which finally engage a small population of neurons in the cortex. This cortical center appears to be dedicated to transduce a neuronal signal reflexively into cerebral vasodilatation and synchronization of electrocortical activity; a fact that seems to be unique among autonomous reflexes. Sympathetic excitation is mediated by cortical-spinal projection to spinal preganglionic sympathetic neurons, whereas bradycardia is mediated via projections to cardiovagal motor medullary neurons. The integrated reflex response serves to redistribute blood from viscera to the brain in response to a challenge to cerebral metabolism, but seems also to initiate a preconditioning mechanism. Previous studies showed a great variability in the human TCR response, in special to external stimuli and individual factors. The TCR gives, therefore, not only new insights into novel therapeutic options for a range of disorders characterized by neuronal death, but also into the cortical and molecular organization of the brain.

  12. Estudio de un modelo de red neuronal artificial del switch molecular del bacteriófago Lambda

    Directory of Open Access Journals (Sweden)

    Rodríguez Tobón Guillermo León

    2006-06-01

    Full Text Available La maquinaria molecular de las células consiste de una enorme red de moléculas que interactúan unas con
    otras de manera compleja. En estos sistemas la información es procesada por medio de variaciones en las
    concentraciones y localización de estas moléculas en respuesta a estímulos de origen intra o extra celular. Una
    de las tendencias más importantes de la biología molecular actual, gira en torno a la comprensión de los procesos de procesamiento de la información por medio de la elaboración de modelos dinámicos sistémicos de los sistemas moleculares biológicos. En los últimos años, grandes adelantos han tenido lugar en el campo del desarrollo e implementación de algoritmos que permiten realizar simulaciones del comportamiento de diversos sistemas moleculares tales como las vías de señalización intracelular, control del metabolismo y expresión genética. En un modelo dinámico sistémico cualquier cantidad de interés, mientras que la medición de las mismas cantidades in vivo requiere la elaboración y ejecución de experimentos muy laboriosos y costosos. La aplicación de las técnicas de modelamiento y simulación en el campo de la biología molecular ayuda al mejoramiento en el entendimiento de los procesos biológicos. Los aspectos moleculares del sistema regulatorio del bacteriófago lambda, ha sido por mucho tiempo el centro de atención de las investigaciones que tratan de dilucidar las bases moleculares de los procesos implicados en el control de expresión genética en procariotas. Aspectos tanto cuantitativos como cualitativos del comportamiento del switch del bacteriófago lambda han sido caracterizados experimentalmente. Sin embargo, un completo  entendimiento de la robustez y estabilidad del sistema regulatorio del mismo está aún por obtenerse. En el presente trabajo se propone  una modificación del modelo dinámico, el cual tiene como elemento principal la dinámica reguladora del operador

  13. Solution-phase laser processing of π-conjugated polymers: Switching between different molecular states

    Science.gov (United States)

    Takada, K.; Tomioka, A.

    2012-04-01

    Liquid-phase laser processing, where the laser-irradiated target material is immersed in water for cooling, has been reported as a promising processing technique for thermally fragile organic materials. Although nanometer-sized particles have been reported to be obtained with the liquid-phase laser processing, the physical property did not change because quantum-mechanical size effect does not exhibit itself in the zero-radius Frenkel excitons. In the present study, we step further to use solution droplets as a target material, where organic molecules are molecularly dispersed in organic solvent and, therefore, expected to easily alter the conformation and the energy state upon laser irradiation. Small volume organic solvent is quickly evaporated upon laser irradiation, letting the bare organic molecule placed in water and rapidly cooled. To prevent the chemical decomposition of the target π-conjugated molecule, the specimen was resonantly irradiated by a ns-pulse green laser, not by a conventional UV laser. When the solid state spin-coat film made from MEH-PPV chloroform solution was used as a irradiation target immersed in water, resulting MEH-PPV particles showed similar photoluminescence (PL) like the PL of the spin-coat film and PL of the chloroform solution, including the 0→1, 0→2 vibrational transitions: this indicates that the energy levels were not modified from the spin-coat film. In comparison, when tiny droplets of MEH-PPV chloroform solution (orange color) were suspended in water, laser irradiation gave rise to yellow MEH-PPV particles which showed 550 nm and 530 nm PL (type B), blue-shifted from the spin-coat film PL 580 nm (type A), suggesting a successful phase transition of MEH-PPV polymer to type B. Further solution-phase laser processing left the type B state unchanged. The irreversible phase transition from type A to type B suggests that the type B ground state has lower energy than type A, which is consistent with the blue-shifted PL of

  14. A conservative region of the mercuric reductase gene (mera) as a molecular marker of bacterial mercury resistance

    Science.gov (United States)

    Sotero-Martins, Adriana; de Jesus, Michele Silva; Lacerda, Michele; Moreira, Josino Costa; Filgueiras, Ana Luzia Lauria; Barrocas, Paulo Rubens Guimarães

    2008-01-01

    The most common bacterial mercury resistance mechanism is based on the reduction of Hg(II) to Hg0, which is dependent of the mercuric reductase enzyme (MerA) activity. The use of a 431 bp fragment of a conservative region of the mercuric reductase (merA) gene was applied as a molecular marker of this mechanism, allowing the identification of mercury resistant bacterial strains. PMID:24031221

  15. Modification of Fluorescent Photoinduced Electron Transfer (PET) Sensors/Switches To Produce Molecular Photo-Ionic Triode Action**

    Science.gov (United States)

    Huxley, Allen J M; Schroeder, Marc; Nimal Gunaratne, H Q; Prasanna de Silva, A

    2014-01-01

    The fluorophore-spacer1-receptor1-spacer2-receptor2 system (where receptor2 alone is photoredox-inactive) shows ionically tunable proton-induced fluorescence off-on switching, which is reminiscent of thermionic triode behavior. This also represents a new extension to modular switch systems based on photoinduced electron transfer (PET) towards the emulation of analogue electronic devices. PMID:24574178

  16. Cardiac contractility structure-activity relationship and ligand-receptor interactions; the discovery of unique and novel molecular switches in myosuppressin signaling.

    Directory of Open Access Journals (Sweden)

    Megan Leander

    Full Text Available Peptidergic signaling regulates cardiac contractility; thus, identifying molecular switches, ligand-receptor contacts, and antagonists aids in exploring the underlying mechanisms to influence health. Myosuppressin (MS, a decapeptide, diminishes cardiac contractility and gut motility. Myosuppressin binds to G protein-coupled receptor (GPCR proteins. Two Drosophila melanogaster myosuppressin receptors (DrmMS-Rs exist; however, no mechanism underlying MS-R activation is reported. We predicted DrmMS-Rs contained molecular switches that resembled those of Rhodopsin. Additionally, we believed DrmMS-DrmMS-R1 and DrmMS-DrmMS-R2 interactions would reflect our structure-activity relationship (SAR data. We hypothesized agonist- and antagonist-receptor contacts would differ from one another depending on activity. Lastly, we expected our study to apply to other species; we tested this hypothesis in Rhodnius prolixus, the Chagas disease vector. Searching DrmMS-Rs for molecular switches led to the discovery of a unique ionic lock and a novel 3-6 lock, as well as transmission and tyrosine toggle switches. The DrmMS-DrmMS-R1 and DrmMS-DrmMS-R2 contacts suggested tissue-specific signaling existed, which was in line with our SAR data. We identified R. prolixus (RhpMS-R and discovered it, too, contained the unique myosuppressin ionic lock and novel 3-6 lock found in DrmMS-Rs as well as transmission and tyrosine toggle switches. Further, these motifs were present in red flour beetle, common water flea, honey bee, domestic silkworm, and termite MS-Rs. RhpMS and DrmMS decreased R. prolixus cardiac contractility dose dependently with EC50 values of 140 nM and 50 nM. Based on ligand-receptor contacts, we designed RhpMS analogs believed to be an active core and antagonist; testing on heart confirmed these predictions. The active core docking mimicked RhpMS, however, the antagonist did not. Together, these data were consistent with the unique ionic lock, novel 3-6 lock

  17. Molecular dynamics simulation reveals conformational switching of water-mediated uracil-cytosine base-pairs in an RNA duplex.

    Science.gov (United States)

    Schneider, C; Brandl, M; Sühnel, J

    2001-01-26

    A 4 ns molecular dynamics simulation of an RNA duplex (r-GGACUUCGGUCC)(2 )in solution with Na+ and Cl- as counterions was performed. The X-ray structure of this duplex includes two water-mediated uracil-cytosine pairs. In contrast to the other base-pairs in the duplex the water-mediated pairs switch between different conformations. One conformation corresponds to the geometry of the water-mediated UC pairs in the duplex X-ray structure with water acting both as hydrogen-bond donor and acceptor. Another conformation is close to that of a water-mediated UC base-pair found in the X-ray structure of the 23 S rRNA sarcin/ricin domain. In this case the oxygen of the water molecule is linked to two-base donor sites. For a very short time also a direct UC base-pair and a further conformation that is similar to the one found in the RNA duplex structure but exhibits an increased H3(U)...N3(C) distance is observed. Water molecules with unusually long residence times are involved in the water-mediated conformations. These results indicate that the dynamic behaviour of the water-mediated UC base-pairs differs from that of the duplex Watson-Crick and non-canonical guanine-uracil pairs with two or three direct hydrogen bonds. The conformational variability and increased flexibility has to be taken into account when considering these base-pairs as RNA building blocks and as recognition motifs. Copyright 2001 Academic Press.

  18. Molecular Orbital Rule for Quantum Interference in Weakly Coupled Dimers: Low-Energy Giant Conductivity Switching Induced by Orbital Level Crossing.

    Science.gov (United States)

    Nozaki, Daijiro; Lücke, Andreas; Schmidt, Wolf Gero

    2017-02-16

    Destructive quantum interference (QI) in molecular junctions has attracted much attention in recent years. It can tune the conductance of molecular devices dramatically, which implies numerous potential applications in thermoelectric and switching applications. There are several schemes that address and rationalize QI in single molecular devices. Dimers play a particular role in this respect because the QI signal may disappear, depending on the dislocation of monomers. We derive a simple rule that governs the occurrence of QI in weakly coupled dimer stacks of both alternant and nonalternant polyaromatic hydrocarbons (PAHs) and extends the Tada-Yoshizawa scheme. Starting from the Green's function formalism combined with the molecular orbital expansion approach, it is shown that QI-induced antiresonances and their energies can be predicted from the amplitudes of the respective monomer terminal molecular orbitals. The condition is illustrated for a toy model consisting of two hydrogen molecules and applied within density functional calculations to alternant dimers of oligo(phenylene-ethynylene) and nonalternant PAHs. Minimal dimer structure modifications that require only a few millielectronvolts and lead to an energy crossing of the essentially preserved monomer orbitals are shown to result in giant conductance switching ratios.

  19. Conformational choreography of a molecular switch region in myelin basic protein--molecular dynamics shows induced folding and secondary structure type conversion upon threonyl phosphorylation in both aqueous and membrane-associated environments.

    Science.gov (United States)

    Polverini, Eugenia; Coll, Eoin P; Tieleman, D Peter; Harauz, George

    2011-03-01

    The 18.5 kDa isoform of myelin basic protein is essential to maintaining the close apposition of myelin membranes in central nervous system myelin, but its intrinsic disorder (conformational dependence on environment), a variety of post-translational modifications, and a diversity of protein ligands (e.g., actin and tubulin) all indicate it to be multifunctional. We have performed molecular dynamics simulations of a conserved central segment of 18.5 kDa myelin basic protein (residues Glu80-Gly103, murine sequence numbering) in aqueous and membrane-associated environments to ascertain the stability of constituent secondary structure elements (α-helix from Glu80-Val91 and extended poly-proline type II from Thr92-Gly103) and the effects of phosphorylation of residues Thr92 and Thr95, individually and together. In aqueous solution, all four forms of the peptide bent in the middle to form a hydrophobic cluster. The phosphorylated variants were stabilized further by electrostatic interactions and formation of β-structures, in agreement with previous spectroscopic data. In simulations performed with the peptide in association with a dimyristoylphosphatidylcholine bilayer, the amphipathic α-helical segment remained stable and membrane-associated, although the degree of penetration was less in the phosphorylated variants, and the tilt of the α-helix with respect to the plane of the membrane also changed significantly with the modifications. The extended segment adjacent to this α-helix represents a putative SH3-ligand and remained exposed to the cytoplasm (and thus accessible to binding partners). The results of these simulations demonstrate how this segment of the protein can act as a molecular switch: an amphipathic α-helical segment of the protein is membrane-associated and presents a subsequent proline-rich segment to the cytoplasm for interaction with other proteins. Phosphorylation of threonyl residues alters the degree of membrane penetration of the

  20. Achieving Energy Conservation in Poisson-Boltzmann Molecular Dynamics: Accuracy and Precision with Finite-Difference Algorithms

    Science.gov (United States)

    Wang, Jun; Cai, Qin; Li, Zhi-Lin; Zhao, Hong-Kai; Luo, Ray

    2009-01-01

    Violation of energy conservation in Poisson-Boltzmann molecular dynamics, due to the limited accuracy and precision of numerical methods, is a major bottleneck preventing its wide adoption in biomolecular simulations. We explored the ideas of enforcing interface conditions by the immerse interface method and of removing charge singularity to improve the finite-difference methods. Our analysis of these ideas on an analytical test system shows significant improvement in both energies and forces. Our analysis further indicates the need for more accurate force calculation, especially the boundary force calculation. PMID:20098487

  1. Effects of molecular chirality on self-assembly and switching in liquid crystals at the cross-over between rod-like and bent shapes.

    Science.gov (United States)

    Ocak, Hale; Poppe, Marco; Bilgin-Eran, Belkız; Karanlık, Gürkan; Prehm, Marko; Tschierske, Carsten

    2016-09-21

    A bent-core compound derived from a 4-cyanoresorcinol core unit with two terephthalate based rod-like wings and carrying chiral 3,7-dimethyloctyloxy side chains has been synthesized in racemic and enantiomerically pure form and characterized by polarizing microscopy, differential scanning calorimetry, X-ray diffraction and electro-optical investigations to study the influence of molecular chirality on the superstructural chirality and polar order in lamellar liquid crystalline phases. Herein we demonstrate that the coupling of molecular chirality with superstructural layer chirality in SmCsPF domain phases (forming energetically distinct diastereomeric pairs) can fix the tilt direction and thus stabilize synpolar order, leading to bistable ferroelectric switching in the SmC* phases of the (S)-enantiomer, whereas tristable modes determine the switching of the racemate. Moreover, the mechanism of electric field induced molecular reorganization changes from a rotation around the molecular long axis in the racemate to a rotation on the tilt-cone for the (S)-enantiomer. At high temperature the enantiomer behaves like a rod-like molecule with a chirality induced ferroelectric SmC* phase and an electroclinic effect in the SmA'* phase. At reduced temperature sterically induced polarization, due to the bent molecular shape, becomes dominating, leading to much higher polarization values, thus providing access to high polarization ferroelectric materials with weakly bent compounds having only "weakly chiral" stereogenic units. Moreover, the field induced alignment of the SmCsPF(()*()) domains gives rise to a special kind of electroclinic effect appearing even in the absence of molecular chirality. Comparison with related compounds indicates that the strongest effects of chirality appear for weakly bent molecules with a relatively short coherence length of polar order, whereas for smectic phases with long range polar order the effects of the interlayer interfaces can override

  2. Molecular dynamics analysis of conserved hydrophobic and hydrophilic bond-interaction networks in ErbB family kinases.

    Science.gov (United States)

    Shih, Andrew J; Telesco, Shannon E; Choi, Sung-Hee; Lemmon, Mark A; Radhakrishnan, Ravi

    2011-06-01

    The EGFR (epidermal growth factor receptor)/ErbB/HER (human EGFR) family of kinases contains four homologous receptor tyrosine kinases that are important regulatory elements in key signalling pathways. To elucidate the atomistic mechanisms of dimerization-dependent activation in the ErbB family, we have performed molecular dynamics simulations of the intracellular kinase domains of three members of the ErbB family (those with known kinase activity), namely EGFR, ErbB2 (HER2) and ErbB4 (HER4), in different molecular contexts: monomer against dimer and wild-type against mutant. Using bioinformatics and fluctuation analyses of the molecular dynamics trajectories, we relate sequence similarities to correspondence of specific bond-interaction networks and collective dynamical modes. We find that in the active conformation of the ErbB kinases, key subdomain motions are co-ordinated through conserved hydrophilic interactions: activating bond-networks consisting of hydrogen bonds and salt bridges. The inactive conformations also demonstrate conserved bonding patterns (albeit less extensive) that sequester key residues and disrupt the activating bond network. Both conformational states have distinct hydrophobic advantages through context-specific hydrophobic interactions. We show that the functional (activating) asymmetric kinase dimer interface forces a corresponding change in the hydrophobic and hydrophilic interactions that characterize the inactivating bond network, resulting in motion of the αC-helix through allostery. Several of the clinically identified activating kinase mutations of EGFR act in a similar fashion to disrupt the inactivating bond network. The present molecular dynamics study reveals a fundamental difference in the sequence of events in EGFR activation compared with that described for the Src kinase Hck.

  3. Heat of molecular chemisorption from bond-order-conservation viewpoint: Why morse potentials are so efficient

    Science.gov (United States)

    Shustorovich, Evgeny

    1987-03-01

    Our analytic Morse-potential model of chemisorption based on bond-order conservation [Surface Sci. 150 (1985) L115; 163 (1985) L730] has been extended to calculate the heat of chemisorption QAZ of molecules AZ coordinated parallel to a metal surface, where A and Z may be either the same or different atoms or atomic groups ("quasiatoms"). Examples include O 2, CO, H 2CCH 2, HCCH, H 2CO, and (CH 3) 2CO, where comparisons with the perpendicular AZ coordinations, considered earlier, are also made. The projected qualitative trends and quantitative estimates are in agreement with (scarce) experiment. It is argued that, within the bond-order-conservation framework, the efficiency of Morse potentials to describe the energetics of various chemisorption phenomena ultimately originates from the zero-energy gap between the occupied and vacant parts of the metal band.

  4. Molecular diversity in Coffea canephora germplasm conserved and cultivated in Brazil

    Directory of Open Access Journals (Sweden)

    Flávio de França Souza

    2013-12-01

    Full Text Available This work aimed to characterize accessions that represent the C. canephora germplasm conserved and cultivated in Brazil. A total of 130 accessions from germplasm banks of IAC (São Paulo, UFV (Minas Gerais and also collected in plantations of the State of Espírito Santo and Rondônia were evaluated with a set of 20 new microsatellite primers. Multivariate methods were used to estimate the relationship among the accessions. High level of polymorphism and two major diversity clusters were identified. First cluster was composed by the accessions conserved in the IAC and UFV collections and the second was formed by accessions collected in areas under cultivation. Accessions from Espírito Santo and Rondônia were clear separated, composing two subclusters. Despite the great polymorphism found in Brazilian plantations, the diversity may be increased, because a new threshold in the genetic gains is expected on breeding programs with the intensification of the use of conserved germplasm.

  5. Synthesis, molecular structure, spectroscopic investigations and computational study of a potential molecular switch of 2-([1,1'-biphenyl]-4-yl)-2-methyl-6-(4-nitrophenyl)-4-phenyl-1,3 diazabicyclo [3.1.0]hex-3-ene

    Indian Academy of Sciences (India)

    AYOUB KANAANI; DAVOOD AJLOO; HAMZEH I KIYAN; FRESHTE SHAHERI; MAJID AMIRI

    2016-08-01

    This work presents a combined experimental and theoretical study on a photochromic compound, 2-([1,1'-biphenyl]-4-yl)-2-methyl-6-(4-nitrophenyl)-4-phenyl-1,3 diazabicyclo [3.1.0]hex-3-ene, existing in closed form (‘A’) and open form (‘B’). The spectroscopic properties of the title compound have beeninvestigated by using IR, UV–Vis and ¹H NMR techniques. The molecular geometry and spectroscopic data of the title compound have been calculated by using the density functional method (B3LYP) invoking 6-311G(d,p) basis set. UV-Vis spectra of the two forms were recorded. The excitation energies, oscillator strength, etc., were calculated by time-dependent density functional theory (TD-DFT). Furthermore, molecular electrostatic potential map (MEP), frontier molecular orbital analysis (HOMO–LUMO), total density of state (TDOS) and reactivity descriptors were found and discussed. We applied a first-principles computational approach to study a light-sensitive molecular switch. We find that the conductance of the two isomers varies dramatically, which suggests that this system has potential use as a molecular switch.

  6. Molecular genetic analysis of the yellow-breasted capuchin monkey: recommendations for ex situ conservation.

    Science.gov (United States)

    Oliveira, C G; Gaiotto, F A; Costa, M A; Martinez, R A

    2011-01-01

    The yellow-breasted capuchin monkey, Cebus xanthosternos, is one of the most endangered species of the Brazilian Atlantic Forest. In situ conservation for this species is problematic due to habitat destruction; therefore, captive conservation has been considered as an alternative strategy. A Studbook for C. xanthosternos has been kept for more than 20 years; however, no genetic data has been collected. Our aim was to provide a preliminary assessment of the genetic variability of C. xanthosternos in captivity in Brazil and compare it with data from the wild. Microsatellite and mtDNA sequencing were carried out in 40 samples from five Brazilian institutions registered in the international Studbook and compared with 8 samples collected in a wild population from REBIO-Una/BA. DNA for analysis was extracted from hair, feces and blood. Our results showed that two of the five captive groups assessed had a genetic variability comparable to wild animals. However, the other three groups apparently require urgent management to improve its genetic variability. Considering that inbreeding effects are more pronounced in captivity due to lack of gene flow, our data indicate a need to increase population size by introducing newly rescued individuals into these captive groups. Our results are the first attempt to provide genetic information for captive C. xanthosternos in Brazil.

  7. Structural polymorphism of the major capsid protein of a double-stranded RNA virus: an amphipathic alpha helix as a molecular switch.

    Science.gov (United States)

    Saugar, Irene; Luque, Daniel; Oña, Ana; Rodríguez, José F; Carrascosa, José L; Trus, Benes L; Castón, José R

    2005-07-01

    The infectious bursal disease virus T=13 viral particle is composed of two major proteins, VP2 and VP3. Here, we show that the molecular basis of the conformational flexibility of the major capsid protein precursor, pVP2, is an amphipatic alpha helix formed by the sequence GFKDIIRAIR. VP2 containing this alpha helix is able to assemble into the T=13 capsid only when expressed as a chimeric protein with an N-terminal His tag. An amphiphilic alpha helix, which acts as a conformational switch, is thus responsible for the inherent structural polymorphism of VP2. The His tag mimics the VP3 C-terminal region closely and acts as a molecular triggering factor. Using cryo-electron microscopy difference imaging, both polypeptide elements were detected on the capsid inner surface. We propose that electrostatic interactions between these two morphogenic elements are transmitted to VP2 to acquire the competent conformations for capsid assembly.

  8. Designs for the self-assembly of open and closed macromolecular structures and a molecular switch using DNA methyltransferases to order proteins on nucleic acid scaffolds

    Science.gov (United States)

    Smith, Steven S.

    2002-06-01

    The methyltransferase-directed addressing of fusion proteins to DNA scaffolds offers an approach to the construction of protein/nucleic acid biostructures with potential in a variety of applications. The technology is currently only limited by the yield of high occupancy structures. However, current evidence shows that DNA scaffolds that contain three or four targeted proteins can be reliably constructed. This permits a variety of macromolecular designs, several of which are given in this paper. Designs for open and closed two-dimensional and three-dimensional assemblies and a design for a molecular switch are discussed. The closed two-dimensional assembly takes the form of a square, and could find application as a component of other systems including a macromolecular rotaxane. The closed three-dimensional system takes the form of a trigonal bipyramid and could find application as a macromolecular carcerand. The molecular switch could find application as a peptide biosensor. Guidelines for the construction and structural verification of these designs are reported.

  9. Genomic Investigation Reveals Highly Conserved, Mosaic, Recombination Events Associated with Capsular Switching among Invasive Neisseria meningitidis Serogroup W Sequence Type (ST)-11 Strains.

    Science.gov (United States)

    Mustapha, Mustapha M; Marsh, Jane W; Krauland, Mary G; Fernandez, Jorge O; de Lemos, Ana Paula S; Dunning Hotopp, Julie C; Wang, Xin; Mayer, Leonard W; Lawrence, Jeffrey G; Hiller, N Luisa; Harrison, Lee H

    2016-07-03

    Neisseria meningitidis is an important cause of meningococcal disease globally. Sequence type (ST)-11 clonal complex (cc11) is a hypervirulent meningococcal lineage historically associated with serogroup C capsule and is believed to have acquired the W capsule through a C to W capsular switching event. We studied the sequence of capsule gene cluster (cps) and adjoining genomic regions of 524 invasive W cc11 strains isolated globally. We identified recombination breakpoints corresponding to two distinct recombination events within W cc11: A 8.4-kb recombinant region likely acquired from W cc22 including the sialic acid/glycosyl-transferase gene, csw resulted in a C→W change in capsular phenotype and a 13.7-kb recombinant segment likely acquired from Y cc23 lineage includes 4.5 kb of cps genes and 8.2 kb downstream of the cps cluster resulting in allelic changes in capsule translocation genes. A vast majority of W cc11 strains (497/524, 94.8%) retain both recombination events as evidenced by sharing identical or very closely related capsular allelic profiles. These data suggest that the W cc11 capsular switch involved two separate recombination events and that current global W cc11 meningococcal disease is caused by strains bearing this mosaic capsular switch.

  10. Conservation of nucleotide sequences for molecular diagnosis of Middle East respiratory syndrome coronavirus, 2015.

    Science.gov (United States)

    Furuse, Yuki; Okamoto, Michiko; Oshitani, Hitoshi

    2015-11-01

    Infection due to the Middle East respiratory syndrome coronavirus (MERS-CoV) is widespread. The present study was performed to assess the protocols used for the molecular diagnosis of MERS-CoV by analyzing the nucleotide sequences of viruses detected between 2012 and 2015, including sequences from the large outbreak in eastern Asia in 2015. Although the diagnostic protocols were established only 2 years ago, mismatches between the sequences of primers/probes and viruses were found for several of the assays. Such mismatches could lead to a lower sensitivity of the assay, thereby leading to false-negative diagnosis. A slight modification in the primer design is suggested. Protocols for the molecular diagnosis of viral infections should be reviewed regularly after they are established, particularly for viruses that pose a great threat to public health such as MERS-CoV.

  11. Conservation of nucleotide sequences for molecular diagnosis of Middle East respiratory syndrome coronavirus, 2015

    Directory of Open Access Journals (Sweden)

    Yuki Furuse

    2015-11-01

    Full Text Available Infection due to the Middle East respiratory syndrome coronavirus (MERS-CoV is widespread. The present study was performed to assess the protocols used for the molecular diagnosis of MERS-CoV by analyzing the nucleotide sequences of viruses detected between 2012 and 2015, including sequences from the large outbreak in eastern Asia in 2015. Although the diagnostic protocols were established only 2 years ago, mismatches between the sequences of primers/probes and viruses were found for several of the assays. Such mismatches could lead to a lower sensitivity of the assay, thereby leading to false-negative diagnosis. A slight modification in the primer design is suggested. Protocols for the molecular diagnosis of viral infections should be reviewed regularly after they are established, particularly for viruses that pose a great threat to public health such as MERS-CoV.

  12. Protocols for In Vitro Propagation, Conservation, Synthetic Seed Production, Microrhizome Production, and Molecular Profiling in Turmeric (Curcuma longa L.).

    Science.gov (United States)

    Nirmal Babu, K; Divakaran, Minoo; Pillai, Geetha S; Sumathi, V; Praveen, K; Raj, Rahul P; Akshita, H J; Ravindran, P N; Peter, K V

    2016-01-01

    Turmeric is a rhizomatous herbaceous perennial but cultivated as annual, belonging to the family Zingiberaceae. It is a native of India and South East Asia. The tuberous rhizomes or underground stems of turmeric are used from antiquity as condiments, a dye and as an aromatic stimulant in several medicines. Turmeric is an important crop in India and it is used as a spice, food preservative, coloring agent, cosmetic as well as for its medicinal properties. Propagation is done vegetatively with rhizome bits as seed materials. It is plagued by rhizome rot diseases most of which are mainly spread through infected seed rhizomes. Micropropagation will help in production of disease-free seed. Sexual reproduction is rare in turmeric, making recombinant breeding very difficult. In vitro technology can thus become the preferred choice and it can be utilized for multiplication, conservation of genetic resources, generating variability, gene transfer, molecular tagging, and their utility in crop improvement.

  13. Molecular studies of Callithrix pygmaea (Primates, Platyrrhini based on transferrin intronic and ND1 regions: implications for taxonomy and conservation

    Directory of Open Access Journals (Sweden)

    Tagliaro Claudia Helena

    2000-01-01

    Full Text Available Traditional classifications of Platyrrhini monkeys, based mainly on morphological features, are being contested by recent molecular data. The subfamily Callitrichinae (Platyrrhini, Primates consists of a diverse group of species, many of them considered endangered. Our analysis of two DNA regions, a mtDNA gene (ND1 and a nuclear gene (intronic regions of the transferrin gene, suggests that Callithrix pygmaea may have sufficient variability to justify the existence of subspecies or even separate species. Phylogenetic dendrograms based on the ND1 region show that this species is more closely related to Amazonian than to Atlantic forest marmosets. These results reopen the discussion about diversity and conservation programs based exclusively on traditional classifications.

  14. Molecular phylogeny of OVOL genes illustrates a conserved C2H2 zinc finger domain coupled by hypervariable unstructured regions.

    Directory of Open Access Journals (Sweden)

    Abhishek Kumar

    Full Text Available OVO-like proteins (OVOL are members of the zinc finger protein family and serve as transcription factors to regulate gene expression in various differentiation processes. Recent studies have shown that OVOL genes are involved in epithelial development and differentiation in a wide variety of organisms; yet there is a lack of comprehensive studies that describe OVOL proteins from an evolutionary perspective. Using comparative genomic analysis, we traced three different OVOL genes (OVOL1-3 in vertebrates. One gene, OVOL3, was duplicated during a whole-genome-duplication event in fish, but only the copy (OVOL3b was retained. From early-branching metazoa to humans, we found that a core domain, comprising a tetrad of C2H2 zinc fingers, is conserved. By domain comparison of the OVOL proteins, we found that they evolved in different metazoan lineages by attaching intrinsically-disordered (ID segments of N/C-terminal extensions of 100 to 1000 amino acids to this conserved core. These ID regions originated independently across different animal lineages giving rise to different types of OVOL genes over the course of metazoan evolution. We illustrated the molecular evolution of metazoan OVOL genes over a period of 700 million years (MY. This study both extends our current understanding of the structure/function relationship of metazoan OVOL genes, and assembles a good platform for further characterization of OVOL genes from diverged organisms.

  15. Are Pharmaceuticals with Evolutionary Conserved Molecular Drug Targets More Potent to Cause Toxic Effects in Non-Target Organisms?

    Science.gov (United States)

    Furuhagen, Sara; Fuchs, Anne; Lundström Belleza, Elin; Breitholtz, Magnus; Gorokhova, Elena

    2014-01-01

    The ubiquitous use of pharmaceuticals has resulted in a continuous discharge into wastewater and pharmaceuticals and their metabolites are found in the environment. Due to their design towards specific drug targets, pharmaceuticals may be therapeutically active already at low environmental concentrations. Several human drug targets are evolutionary conserved in aquatic organisms, raising concerns about effects of these pharmaceuticals in non-target organisms. In this study, we hypothesized that the toxicity of a pharmaceutical towards a non-target invertebrate depends on the presence of the human drug target orthologs in this species. This was tested by assessing toxicity of pharmaceuticals with (miconazole and promethazine) and without (levonorgestrel) identified drug target orthologs in the cladoceran Daphnia magna. The toxicity was evaluated using general toxicity endpoints at individual (immobility, reproduction and development), biochemical (RNA and DNA content) and molecular (gene expression) levels. The results provide evidence for higher toxicity of miconazole and promethazine, i.e. the drugs with identified drug target orthologs. At the individual level, miconazole had the lowest effect concentrations for immobility and reproduction (0.3 and 0.022 mg L−1, respectively) followed by promethazine (1.6 and 0.18 mg L−1, respectively). At the biochemical level, individual RNA content was affected by miconazole and promethazine already at 0.0023 and 0.059 mg L−1, respectively. At the molecular level, gene expression for cuticle protein was significantly suppressed by exposure to both miconazole and promethazine; moreover, daphnids exposed to miconazole had significantly lower vitellogenin expression. Levonorgestrel did not have any effects on any endpoints in the concentrations tested. These results highlight the importance of considering drug target conservation in environmental risk assessments of pharmaceuticals. PMID:25140792

  16. Are pharmaceuticals with evolutionary conserved molecular drug targets more potent to cause toxic effects in non-target organisms?

    Directory of Open Access Journals (Sweden)

    Sara Furuhagen

    Full Text Available The ubiquitous use of pharmaceuticals has resulted in a continuous discharge into wastewater and pharmaceuticals and their metabolites are found in the environment. Due to their design towards specific drug targets, pharmaceuticals may be therapeutically active already at low environmental concentrations. Several human drug targets are evolutionary conserved in aquatic organisms, raising concerns about effects of these pharmaceuticals in non-target organisms. In this study, we hypothesized that the toxicity of a pharmaceutical towards a non-target invertebrate depends on the presence of the human drug target orthologs in this species. This was tested by assessing toxicity of pharmaceuticals with (miconazole and promethazine and without (levonorgestrel identified drug target orthologs in the cladoceran Daphnia magna. The toxicity was evaluated using general toxicity endpoints at individual (immobility, reproduction and development, biochemical (RNA and DNA content and molecular (gene expression levels. The results provide evidence for higher toxicity of miconazole and promethazine, i.e. the drugs with identified drug target orthologs. At the individual level, miconazole had the lowest effect concentrations for immobility and reproduction (0.3 and 0.022 mg L-1, respectively followed by promethazine (1.6 and 0.18 mg L-1, respectively. At the biochemical level, individual RNA content was affected by miconazole and promethazine already at 0.0023 and 0.059 mg L-1, respectively. At the molecular level, gene expression for cuticle protein was significantly suppressed by exposure to both miconazole and promethazine; moreover, daphnids exposed to miconazole had significantly lower vitellogenin expression. Levonorgestrel did not have any effects on any endpoints in the concentrations tested. These results highlight the importance of considering drug target conservation in environmental risk assessments of pharmaceuticals.

  17. Are pharmaceuticals with evolutionary conserved molecular drug targets more potent to cause toxic effects in non-target organisms?

    Science.gov (United States)

    Furuhagen, Sara; Fuchs, Anne; Lundström Belleza, Elin; Breitholtz, Magnus; Gorokhova, Elena

    2014-01-01

    The ubiquitous use of pharmaceuticals has resulted in a continuous discharge into wastewater and pharmaceuticals and their metabolites are found in the environment. Due to their design towards specific drug targets, pharmaceuticals may be therapeutically active already at low environmental concentrations. Several human drug targets are evolutionary conserved in aquatic organisms, raising concerns about effects of these pharmaceuticals in non-target organisms. In this study, we hypothesized that the toxicity of a pharmaceutical towards a non-target invertebrate depends on the presence of the human drug target orthologs in this species. This was tested by assessing toxicity of pharmaceuticals with (miconazole and promethazine) and without (levonorgestrel) identified drug target orthologs in the cladoceran Daphnia magna. The toxicity was evaluated using general toxicity endpoints at individual (immobility, reproduction and development), biochemical (RNA and DNA content) and molecular (gene expression) levels. The results provide evidence for higher toxicity of miconazole and promethazine, i.e. the drugs with identified drug target orthologs. At the individual level, miconazole had the lowest effect concentrations for immobility and reproduction (0.3 and 0.022 mg L-1, respectively) followed by promethazine (1.6 and 0.18 mg L-1, respectively). At the biochemical level, individual RNA content was affected by miconazole and promethazine already at 0.0023 and 0.059 mg L-1, respectively. At the molecular level, gene expression for cuticle protein was significantly suppressed by exposure to both miconazole and promethazine; moreover, daphnids exposed to miconazole had significantly lower vitellogenin expression. Levonorgestrel did not have any effects on any endpoints in the concentrations tested. These results highlight the importance of considering drug target conservation in environmental risk assessments of pharmaceuticals.

  18. Molecular phylogenetics of geographically restricted Acropora species: implications for threatened species conservation.

    Science.gov (United States)

    Richards, Z T; Miller, D J; Wallace, C C

    2013-12-01

    To better understand the underlying causes of rarity and extinction risk in Acropora (staghorn coral), we contrast the minimum divergence ages and nucleotide diversity of an array of species with different range sizes and levels of threat. Time-calibrated Bayesian analyses based upon concatenated nuclear and mitochondrial sequence data implied contemporary range size and vulnerability are linked to species age. However, contrary to previous hypotheses that suggest geographically restricted Acropora species evolved in the Plio-Pleistocene, the molecular phylogeny depicts some Indo-Australian species have greater antiquity, diverging in the Miocene. Species age is not related to range size as a simple positive linear function and interpreting the precise tempo of evolution in this genus is greatly complicated by morphological homoplasy and a sparse fossil record. Our phylogenetic reconstructions provide new examples of how morphology conceals cryptic evolutionary relationships in this keystone genus, and offers limited support for the species groupings currently used in Acropora systematics. We hypothesize that in addition to age, other mechanisms (such as a reticulate ancestry) delimit the contemporary range of some Acropora species, as evidenced by the complex patterns of allele sharing and paraphyly we uncover. Overall, both new and ancient evolutionary information may be lost if geographically restricted and threatened Acropora species are forced to extinction. In order to protect coral biodiversity and resolve the evolutionary history of staghorn coral, further analyses based on comprehensive and heterogeneous morphological and molecular data utilizing reticulate models of evolution are needed. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. What makes Ras an efficient molecular switch: a computational, biophysical, and structural study of Ras-GDP interactions with mutants of Raf.

    Science.gov (United States)

    Filchtinski, Daniel; Sharabi, Oz; Rüppel, Alma; Vetter, Ingrid R; Herrmann, Christian; Shifman, Julia M

    2010-06-11

    Ras is a small GTP-binding protein that is an essential molecular switch for a wide variety of signaling pathways including the control of cell proliferation, cell cycle progression and apoptosis. In the GTP-bound state, Ras can interact with its effectors, triggering various signaling cascades in the cell. In the GDP-bound state, Ras looses its ability to bind to known effectors. The interaction of the GTP-bound Ras (Ras(GTP)) with its effectors has been studied intensively. However, very little is known about the much weaker interaction between the GDP-bound Ras (Ras(GDP)) and Ras effectors. We investigated the factors underlying the nucleotide-dependent differences in Ras interactions with one of its effectors, Raf kinase. Using computational protein design, we generated mutants of the Ras-binding domain of Raf kinase (Raf) that stabilize the complex with Ras(GDP). Most of our designed mutations narrow the gap between the affinity of Raf for Ras(GTP) and Ras(GDP), producing the desired shift in binding specificity towards Ras(GDP). A combination of our best designed mutation, N71R, with another mutation, A85K, yielded a Raf mutant with a 100-fold improvement in affinity towards Ras(GDP). The Raf A85K and Raf N71R/A85K mutants were used to obtain the first high-resolution structures of Ras(GDP) bound to its effector. Surprisingly, these structures reveal that the loop on Ras previously termed the switch I region in the Ras(GDP).Raf mutant complex is found in a conformation similar to that of Ras(GTP) and not Ras(GDP). Moreover, the structures indicate an increased mobility of the switch I region. This greater flexibility compared to the same loop in Ras(GTP) is likely to explain the natural low affinity of Raf and other Ras effectors to Ras(GDP). Our findings demonstrate that an accurate balance between a rigid, high-affinity conformation and conformational flexibility is required to create an efficient and stringent molecular switch. Copyright 2010 Elsevier Ltd

  20. A molecular marker for in situ genetic resource conservation of Capsicum annuum var. acuminatum (Solanaceae).

    Science.gov (United States)

    Kaewdoungdee, N; Tanee, T

    2013-02-28

    The Thailand cultivar pepper 'phrik man bangchang' (Capsicum annuum var. acuminatum, Solanaceae) was originally cultivated in the Bangchang Subdistrict, Amphawa District in Samut Songkhram Province. The cultivated areas are limited; we verified its distribution in Thailand for in situ 'phrik man bangchang' genetic resource conservation. Samples were collected from the original cultivation area of Bangchang Subdistrict (Or) and were randomly explored in Ratchaburi Province (RB), Khon Kaen Province (KK), and Sakon Nakhon Province (SN). A pure line from The Tropical Vegetable Research Center at Kasetsart University was used as the standard indicator. Two more Capsicum species, C. chinensis and C. frutescens, and a species from another genus in the family, Solanum melongena, were included. A dendrogram constructed from random amplified polymorphic DNA fingerprints indicated that the Or, RB, KK, and SN samples were C. annuum var. acuminatum with supportive similarity coefficients of 0.79 to 0.98. Finally, DNA barcodes, from psbA-trnH spacer region, were provided for the 3 wild species, C. annuum var. acuminatum, C. chinensis, and C. frutescens under GenBank accession Nos. JQ087869-JQ087871. The nucleotide variations between species were 0.23 to 0.26. In summary, 'phrik man bangchang' is still being planted in Bangchang Subdistrict, but only in small areas. The distribution of planting areas is expected to be throughout Thailand.

  1. Residue conservation and dimer-interface analysis of olfactory receptor molecular models

    Directory of Open Access Journals (Sweden)

    Ramanathan Sowdhamini

    2012-10-01

    Full Text Available Olfactory Receptors (ORs are members of the Class A rhodopsin like G-protein coupled receptors (GPCRs which are the initial players in the signal transduction cascade, leading to the generation of nerve impulses transmitted to the brain and resulting in the detection of odorant molecules. Despite the accumulation of thousands of olfactory receptor sequences, no crystal structures of ORs are known tο date. However, the recent availability of crystallographic models of a few GPCRs allows us to generate homology models of ORs and analyze their amino acid patterns, as there is a huge diversity in OR sequences. In this study, we have generated three-dimensional models of 100 representative ORs from Homo sapiens, Mus musculus, Drosophila melanogaster, Caenorhabditis elegans and Sacharomyces cerevisiae which were selected on the basis of a composite classification scheme and phylogenetic analysis. The crystal structure of bovine rhodopsin was used as a template and it was found that the full-length models have more than 90% of their residues in allowed regions of the Ramachandran plot. The structures were further used for analysis of conserved residues in the transmembrane and extracellular loop regions in order to identify functionally important residues. Several ORs are known to be functional as dimers and hence dimer interfaces were predicted for OR models to analyse their oligomeric functional state.

  2. Method for Systematic Assessment of Chemical Changes in Molecular Scaffolds with Conserved Topology and Application to the Analysis of Scaffold-Activity Relationships.

    Science.gov (United States)

    Hu, Ye; Zhang, Bijun; Bajorath, Jürgen

    2015-08-01

    Sets of scaffolds with conserved molecular topology are abundant among drugs and bioactive compounds. Core structure topology is one of the determinants of biological activity. Heteroatom replacements and/or bond order variation render topologically equivalent scaffolds chemically distinct and also contribute to differences in the biological activity of compounds containing these scaffolds. Relationships between core structure topology, chemical modifications, and observed activity profiles are difficult to analyze. A computational method is introduced to consistently assess chemical transformations that distinguish scaffolds with conserved topology. The methodology is applied to quantify chemical differences in conserved topological environments and systematically relate chemical changes in topologically equivalent scaffolds to associated activity profiles.

  3. An acidic loop and cognate phosphorylation sites define a molecular switch that modulates ubiquitin charging activity in Cdc34-like enzymes

    DEFF Research Database (Denmark)

    Papaleo, Elena; Ranzani, Valeria; Tripodi, Farida;

    2011-01-01

    elements in one of the larger families of E2 enzymes: an acidic insertion in β4α2 loop in the proximity of the catalytic cysteine and two conserved key serine residues within the catalytic domain, which are phosphorylated by CK2. Our investigations, using yeast Cdc34 as a model, through 2.5 µs molecular......E2 ubiquitin-conjugating enzymes are crucial mediators of protein ubiquitination, which strongly influence the ultimate fate of the target substrates. Recently, it has been shown that the activity of several enzymes of the ubiquitination pathway is finely tuned by phosphorylation, an ubiquitous...... mechanism for cellular regulation, which modulates protein conformation. In this contribution, we provide the first rationale, at the molecular level, of the regulatory mechanism mediated by casein kinase 2 (CK2) phosphorylation of E2 Cdc34-like enzymes. In particular, we identify two co-evolving signature...

  4. Exciter switch

    Science.gov (United States)

    Mcpeak, W. L.

    1975-01-01

    A new exciter switch assembly has been installed at the three DSN 64-m deep space stations. This assembly provides for switching Block III and Block IV exciters to either the high-power or 20-kW transmitters in either dual-carrier or single-carrier mode. In the dual-carrier mode, it provides for balancing the two drive signals from a single control panel located in the transmitter local control and remote control consoles. In addition to the improved switching capabilities, extensive monitoring of both the exciter switch assembly and Transmitter Subsystem is provided by the exciter switch monitor and display assemblies.

  5. Switch wear leveling

    Science.gov (United States)

    Wu, Hunter; Sealy, Kylee; Gilchrist, Aaron

    2015-09-01

    An apparatus for switch wear leveling includes a switching module that controls switching for two or more pairs of switches in a switching power converter. The switching module controls switches based on a duty cycle control technique and closes and opens each switch in a switching sequence. The pairs of switches connect to a positive and negative terminal of a DC voltage source. For a first switching sequence a first switch of a pair of switches has a higher switching power loss than a second switch of the pair of switches. The apparatus includes a switch rotation module that changes the switching sequence of the two or more pairs of switches from the first switching sequence to a second switching sequence. The second switch of a pair of switches has a higher switching power loss than the first switch of the pair of switches during the second switching sequence.

  6. Utilization of molecular markers for the conservation of blood cockles, Anadara granosa (Arcidae).

    Science.gov (United States)

    Chee, S Y; Azizah, M N S; Devakie, M N

    2011-06-28

    We examined genetic variation in blood cockles in an effort to obtain information useful for the sustainability, management, and the stability of this species as a major commodity in the fisheries sector. Ten populations of cockles were sampled from the north to the south of the west coast of peninsular Malaysia. The cockles were collected in collaboration with the Fisheries Research Institute, Penang. The population genetic analysis of the cockles were studied via RAPD-PCR and mtDNA sequencing. Three hundred individuals were analyzed with RAPD-PCR experiments. High gene diversity over all loci was observed (Shannon index = 0.549 ± 0.056 and Nei's gene diversity = 0.4852 ± 0.0430 among 35 loci). The second method, mtDNA sequencing, was employed to complement the information obtained from RAPD-PCR. The gene selected for mtDNA sequencing was cytochrome c oxidase I (COI). One hundred and fifty individuals were sequenced, yielding a partial gene of 585 bp. Statistical analysis showed homogeneity in general but did reveal some degree of variability between the populations in Johor and the rest of the populations. The Mantel test showed a positive but nonsignificant correlation between geographic and genetic distances (r = 0.2710, P = 0.622), as in the RAPD analysis. We propose that the homogeneity between distant populations is caused by two factors: 1) the translocation of the spats; 2) larvae are carried by current movement from the north of the peninsula to the south. The different genetic composition found in Johor could be due to pollution, mutagenic substances or physical factors such as the depth of the water column. This population genetic study is the first for this species in peninsular Malaysia. The data from this study have important implications for fishery management, conservation of blood cockles and translocation policies for aquaculture and stock enhancement programs.

  7. Molecular Basis for Enzymatic Sulfite Oxidation -- HOW THREE CONSERVED ACTIVE SITE RESIDUES SHAPE ENZYME ACTIVITY

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, Susan; Rapson, Trevor; Johnson-Winters, Kayunta; Astashkin, Andrei; Enemark, John; Kappler, Ulrike

    2008-11-10

    Sulfite dehydrogenases (SDHs) catalyze the oxidation and detoxification of sulfite to sulfate, a reaction critical to all forms of life. Sulfite-oxidizing enzymes contain three conserved active site amino acids (Arg-55, His-57, and Tyr-236) that are crucial for catalytic competency. Here we have studied the kinetic and structural effects of two novel and one previously reported substitution (R55M, H57A, Y236F) in these residues on SDH catalysis. Both Arg-55 and His-57 were found to have key roles in substrate binding. An R55M substitution increased Km(sulfite)(app) by 2-3 orders of magnitude, whereas His-57 was required for maintaining a high substrate affinity at low pH when the imidazole ring is fully protonated. This effect may be mediated by interactions of His-57 with Arg-55 that stabilize the position of the Arg-55 side chain or, alternatively, may reflect changes in the protonation state of sulfite. Unlike what is seen for SDHWT and SDHY236F, the catalytic turnover rates of SDHR55M and SDHH57A are relatively insensitive to pH (~;;60 and 200 s-1, respectively). On the structural level, striking kinetic effects appeared to correlate with disorder (in SDHH57A and SDHY236F) or absence of Arg-55 (SDHR55M), suggesting that Arg-55 and the hydrogen bonding interactions it engages in are crucial for substrate binding and catalysis. The structure of SDHR55M has sulfate bound at the active site, a fact that coincides with a significant increase in the inhibitory effect of sulfate in SDHR55M. Thus, Arg-55 also appears to be involved in enabling discrimination between the substrate and product in SDH.

  8. New concepts in molecular imaging: non-invasive MRI spotting of proteolysis using an Overhauser effect switch.

    Directory of Open Access Journals (Sweden)

    Philippe Mellet

    Full Text Available BACKGROUND: Proteolysis, involved in many processes in living organisms, is tightly regulated in space and time under physiological conditions. However deregulation can occur with local persistent proteolytic activities, e.g. in inflammation, cystic fibrosis, tumors, or pancreatitis. Furthermore, little is known about the role of many proteases, hence there is a need of new imaging methods to visualize specifically normal or disease-related proteolysis in intact bodies. METHODOLOGY/PRINCIPAL FINDINGS: In this paper, a new concept for non invasive proteolysis imaging is proposed. Overhauser-enhanced Magnetic Resonance Imaging (OMRI at 0.2 Tesla was used to monitor the enzymatic hydrolysis of a nitroxide-labeled protein. In vitro, image intensity switched from 1 to 25 upon proteolysis due to the associated decrease in the motional correlation time of the substrate. The OMRI experimental device used in this study is consistent with protease imaging in mice at 0.2 T without significant heating. Simulations show that this enzymatic-driven OMRI signal switch can be obtained at lower frequencies suitable for larger animals or humans. CONCLUSIONS/SIGNIFICANCE: The method is highly sensitive and makes possible proteolysis imaging in three dimensions with a good spatial resolution. Any protease could be targeted specifically through the use of taylor-made cleavable macromolecules. At short term OMRI of proteolysis may be applied to basic research as well as to evaluate therapeutic treatments in small animal models of experimental diseases.

  9. Photoelectron spectroscopy of self-assembled monolayers of molecular switches on noble metal surfaces; Photoelektronenspektroskopie selbstorganisierter Adsorbatschichten aus molekularen Schaltern auf Edelmetalloberflaechen

    Energy Technology Data Exchange (ETDEWEB)

    Heinemann, Nils

    2012-09-12

    Self-assembled monolayers (SAMs) of butanethiolate (C4) on single crystalline Au(111) surfaces were prepared by adsorption from solution. The thermally activated desorption behaviour of the C4 molecules from the gold substrate was examined by qualitative thermal desorption measurements (TDM), through this a desorption temperature T{sub Des}=473 K could be determined. With this knowledge, it was possible to produce samples of very good surface quality, by thermal treatment T{sub Sample}molecular switch 3-(4-(4-Hexyl-phenylazo)-phenoxy)-propane-1-thiol (ABT), deposited by self-assembly from solution on Au(111), was examined using laser-based photoelectron spectroscopy. Differences in the molecular dipole moment characteristic for the trans and the cis isomer of ABT were observed via changes in the sample work function, accessible by detection of the threshold energy for photoemission. A quantitative

  10. A highly conserved glycine within linker I and the extreme C terminus of G protein alpha subunits interact cooperatively in switching G protein-coupled receptor-to-effector specificity

    DEFF Research Database (Denmark)

    Kostenis, Evi; Martini, Lene; Ellis, James;

    2004-01-01

    Numerous studies have attested to the importance of the extreme C terminus of G protein alpha subunits in determining their selectivity of receptor recognition. We have previously reported that a highly conserved glycine residue within linker I is important for constraining the fidelity of receptor...... recognition by Galpha(q) proteins. Herein, we explored whether both modules (linker I and extreme C terminus) interact cooperatively in switching G protein-coupled receptor (GPCR)-to-effector specificity and created as models mutant Galpha(q) proteins in which glycine was replaced with various amino acids...... and the C-terminal five Galpha(q) residues with the corresponding Galpha(i) or Galpha(s) sequence. Coupling properties of the mutated Galpha(q) proteins were determined after coexpression with a panel of 13 G(i)-and G(s) -selective receptors and compared with those of Galpha proteins modified in only one...

  11. Buffering by gene duplicates: an analysis of molecular correlates and evolutionary conservation

    Directory of Open Access Journals (Sweden)

    Vogel Christine

    2008-12-01

    Full Text Available Abstract Background One mechanism to account for robustness against gene knockouts or knockdowns is through buffering by gene duplicates, but the extent and general correlates of this process in organisms is still a matter of debate. To reveal general trends of this process, we provide a comprehensive comparison of gene essentiality, duplication and buffering by duplicates across seven bacteria (Mycoplasma genitalium, Bacillus subtilis, Helicobacter pylori, Haemophilus influenzae, Mycobacterium tuberculosis, Pseudomonas aeruginosa, Escherichia coli, and four eukaryotes (Saccharomyces cerevisiae (yeast, Caenorhabditis elegans (worm, Drosophila melanogaster (fly, Mus musculus (mouse. Results In nine of the eleven organisms, duplicates significantly increase chances of survival upon gene deletion (P-value ≤ 0.05, but only by up to 13%. Given that duplicates make up to 80% of eukaryotic genomes, the small contribution is surprising and points to dominant roles of other buffering processes, such as alternative metabolic pathways. The buffering capacity of duplicates appears to be independent of the degree of gene essentiality and tends to be higher for genes with high expression levels. For example, buffering capacity increases to 23% amongst highly expressed genes in E. coli. Sequence similarity and the number of duplicates per gene are weak predictors of the duplicate's buffering capacity. In a case study we show that buffering gene duplicates in yeast and worm are somewhat more similar in their functions than non-buffering duplicates and have increased transcriptional and translational activity. Conclusion In sum, the extent of gene essentiality and buffering by duplicates is not conserved across organisms and does not correlate with the organisms' apparent complexity. This heterogeneity goes beyond what would be expected from differences in experimental approaches alone. Buffering by duplicates contributes to robustness in several organisms

  12. Formation of body appendages during caudal regeneration in Platynereis dumerilii: adaptation of conserved molecular toolsets

    Directory of Open Access Journals (Sweden)

    Jan Grimmel

    2016-04-01

    Pdu-sp/btd expression is observed in Platynereis. Pdu-dpp shows an expression pattern not comparable to its expression in other taxa. Conclusions The expression patterns observed suggest conserved roles of these genes during appendage formation across different clades, but the underlying mechanisms utilizing this toolset might not be identical. Some genes show broad expression along the proximodistal axis indicating a possible role in proximodistal patterning of body appendages. Other genes exhibit expression patterns limited to specific parts and tissues of the growing parapodia, thus presumably being involved in formation of taxon-specific morphological differences.

  13. Molecular genetic insights on cheetah (Acinonyx jubatus) ecology and conservation in Namibia.

    Science.gov (United States)

    Marker, Laurie L; Pearks Wilkerson, Alison J; Sarno, Ronald J; Martenson, Janice; Breitenmoser-Würsten, Christian; O'Brien, Stephen J; Johnson, Warren E

    2008-01-01

    The extent and geographic patterns of molecular genetic diversity of the largest remaining free-ranging cheetah population were described in a survey of 313 individuals from throughout Namibia. Levels of relatedness, including paternity/maternity (parentage), were assessed across all individuals using 19 polymorphic microsatellite loci, and unrelated cheetahs (n = 89) from 7 regions were genotyped at 38 loci to document broad geographical patterns. There was limited differentiation among regions, evidence that this is a generally panmictic population. Measures of genetic variation were similar among all regions and were comparable with Eastern African cheetah populations. Parentage analyses confirmed several observations based on field studies, including 21 of 23 previously hypothesized family groups, 40 probable parent/offspring pairs, and 8 sibling groups. These results also verified the successful integration and reproduction of several cheetahs following natural dispersal or translocation. Animals within social groups (family groups, male coalitions, or sibling groups) were generally related. Within the main study area, radio-collared female cheetahs were more closely interrelated than similarly compared males, a pattern consistent with greater male dispersal. The long-term maintenance of current patterns of genetic variation in Namibia depends on retaining habitat characteristics that promote natural dispersal and gene flow of cheetahs.

  14. Molecular phylogeny and biogeography of the weevil subfamily Platypodinae reveals evolutionarily conserved range patterns.

    Science.gov (United States)

    Jordal, Bjarte H

    2015-11-01

    Platypodinae is a peculiar weevil subfamily of species that cultivate fungi in tunnels excavated in dead wood. Their geographical distribution is generally restricted, with genera confined to a single continent or large island, which provides a useful system for biogeographical research. This study establishes the first detailed molecular phylogeny of the group, with the aim of testing hypotheses on classification, diversification, and biogeography. A phylogeny was reconstructed based on 3648 nucleotides from COI, EF-1α, CAD, ArgK, and 28S. Tree topology was well resolved and indicated a strong correlation with geography, more so than predicted by previous morphology-based classifications. Tesserocerini was paraphyletic, with Notoplatypus as the sister group to a clade consisting of three main lineages of Tesserocerini and the recently evolved Platypodini. Austroplatypus formed the sister group to all remaining Platypodini and hence confirmed its separate status from Platypus. The Indo-Australian genera of Platypodini were strikingly paraphyletic, suggesting that the taxonomy of this tribe needs careful revision. Ancestral-area reconstructions in Lagrange and S-DIVA were ambiguous for nodes roughly older than 80 Ma. More recent events were firmly assessed and involved post-Gondwanan long-distance dispersal. The Neotropics was colonized three times, all from the Afrotropical region, with the latest event less than 25 Ma that included the ancestor of all Neotropical Platypodini. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. 全氟环戊二芳基乙烯多功能分子开关的研究进展%Progress in multifunctional molecular switches of perfluorocylopentene derivatives

    Institute of Scientific and Technical Information of China (English)

    范丛斌; 章洛汗; 蒲守智

    2011-01-01

    全氟环戊二芳基乙烯是近年来国内外备受关注的一类光致变色化合物.其优良的热稳定性、抗疲劳性,使其很有可能成为一种新型的超高密度信息存储、分子开关及光通信材料.主要介绍了该类化合物的结构异构所表现的不同特性的光/热控分子开关、电化学开关、荧光开关、手性开关和液晶等分子开关,并展望了该类化合物的发展前景.%Perfluorocyctopentene derivative is one of photochromic compounds, which has attracted considerable interest of research because of their thermally irreversible and fatigue resistance properties for use in optoelectronic devices such as ultrahigh-density optical data storage, molecular switches and optical communication. This article describes recent development of multifunctional-switchable perfluorocyclopentene derivatives,which show different isomer properties including photo/hot irradiation molecular switches, electrochemical switches, fluorescent photo-switches, photoirradiation chiral switches and liquid crystalline switches. Future development is prospected finally.

  16. Mode switching of a self-propelled camphor disk sensitive to the photoisomerization of a molecular layer on water.

    Science.gov (United States)

    Nakata, Satoshi; Miyaji, Tatsuya; Matsuda, Yui; Yoshii, Miyu; Abe, Manabu

    2014-07-01

    A simple self-propelled motor on a 4-[[(dodecyloxy)benz-4-yl]azo]benzoic acid (DBA) molecular layer was investigated from the viewpoint of motor control depending on the molecular structure. The nature of the self-motion of a camphor disk on the DBA molecular layer changed depending on the surface pressure (π)-area (A) isotherm of DBA, which in turn changed by the photoisomerization between UV and green lights. The characteristic motion of the camphor disk is discussed in relation to the π-A isotherm of DBA, which changes depending on the photoisomerization as the driving force of motion.

  17. Conserved Molecular and Epigenetic Determinants of Aromatase Gene Induction by the Herbicide Atrazine in Human and Rat Cellular Models Relevant to Breast Cancer Risk

    OpenAIRE

    2011-01-01

    AbstractConserved Molecular and Epigenetic Determinants of Aromatase Gene Induction by the Herbicide Atrazine in Human and Rat Cellular Models Relevant to Breast Cancer Risk ByTheresa Ryan StueveDoctor of Philosophy in Molecular ToxicologyUniversity of California, BerkeleyProfessor Gary Firestone, Co-ChairProfessor Dale Leitman, Co-ChairFall 2011The widely-applied herbicide atrazine (ATR) is a potent endocrine disruptor that elicits anti-androgenic and estrogenic effects, often at concentrat...

  18. A mathematical model for apoptotic switch in Drosophila

    Science.gov (United States)

    Ziraldo, Riccardo; Ma, Lan

    2015-10-01

    Apoptosis is an evolutionarily-conserved process of autonomous cell death. The molecular switch mechanism underlying the fate decision of apoptosis in mammalian cells has been intensively studied by mathematical modeling. In contrast, the apoptotic switch in invertebrates, with highly conserved signaling proteins and pathway, remains poorly understood mechanistically and calls for theoretical elucidation. In this study, we develop a mathematical model of the apoptosis pathway in Drosophila and compare the switch mechanism to that in mammals. Enumeration of the elementary reactions for the model demonstrates that the molecular interactions among the signaling components are considerably different from their mammalian counterparts. A notable distinction in network organization is that the direct positive feedback from the effector caspase (EC) to the initiator caspase in mammalian pathway is replaced by a double-negative regulation in Drosophila. The model is calibrated by experimental input-output relationship and the simulated trajectories exhibit all-or-none bimodal behavior. Bifurcation diagrams confirm that the model of Drosophila apoptotic switch possesses bistability, a well-recognized feature for an apoptosis system. Since the apoptotic protease activating factor-1 (APAF1) induced irreversible activation of caspase is an essential and beneficial property for the mammalian apoptotic switch, we perform analysis of the bistable caspase activation with respect to the input of DARK protein, the Drosophila homolog of APAF1. Interestingly, this bistable behavior in Drosophila is predicted to be reversible. Further analysis suggests that the mechanism underlying the systems property of reversibility is the double-negative feedback from the EC to the initiator caspase. Using theoretical modeling, our study proposes plausible evolution of the switch mechanism for apoptosis between organisms.

  19. Acid/Base and H2PO4(-) Controllable High-Contrast Optical Molecular Switches with a Novel BODIPY Functionalized [2]Rotaxane.

    Science.gov (United States)

    Arumugaperumal, Reguram; Srinivasadesikan, Venkatesan; Ramakrishnam Raju, Mandapati V; Lin, Ming-Chang; Shukla, Tarun; Singh, Ravinder; Lin, Hong-Cheu

    2015-12-09

    A novel multifunctional mechanically interlocked switchable [2]rotaxane R4 containing two molecular stations and rotaxane arms terminated with boron-dipyrromethene (BODIPY) fluorophores and its derivatives were synthesized for the first time by CuAAC click reaction. The shuttling motion of macrocycle between the dibenzylammonium and triazolium recognition sites and the distance dependent photoinduced electron transfer process of R4 is demonstrated by utilizing external chemical stimuli (acid/base). Interestingly, the reversible self-assembly process of R4 was recognized by the acid-base molecular switch strategy. Notably, two symmetrical triazolium groups acted as molecular stations, H2PO4(-) receptors, and H-bonded donors. Both [2]rotaxane R4 and thread R2 demonstrated excellent optical responses and high selectivity toward H2PO4(-) ion. The specific motion and guest-host interactions of mechanically interlocked machines (MIMs) were also further explored by quantum mechanical calculations. The thread R2 also demonstrated to enable the detection of H2PO4(-) in RAW 264.7 cells successfully.

  20. Reversible Switching of Redox-Active Molecular Orbitals and Electron Transfer Pathways in Cu(A) Sites of Cytochrome c Oxidase.

    Science.gov (United States)

    Zitare, Ulises; Alvarez-Paggi, Damián; Morgada, Marcos N; Abriata, Luciano A; Vila, Alejandro J; Murgida, Daniel H

    2015-08-10

    The Cu(A) site of cytochrome c oxidase is a redox hub that participates in rapid electron transfer at low driving forces with two redox cofactors in nearly perpendicular orientations. Spectroscopic and electrochemical characterizations performed on first and second-sphere mutants have allowed us to experimentally detect the reversible switching between two alternative electronic states that confer different directionalities to the redox reaction. Specifically, the M160H variant of a native Cu(A) shows a reversible pH transition that allows to functionally probe both states in the same protein species. Alternation between states exerts a dramatic impact on the kinetic redox parameters, thereby suggesting this effect as the mechanism underlying the efficiency and directionality of Cu(A) electron transfer in vivo. These findings may also prove useful for the development of molecular electronics. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Molecular mimicry by an F-box effector of Legionella pneumophila hijacks a conserved polyubiquitination machinery within macrophages and protozoa.

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    Christopher T Price

    2009-12-01

    Full Text Available The ability of Legionella pneumophila to proliferate within various protozoa in the aquatic environment and in macrophages indicates a remarkable evolution and microbial exploitation of evolutionarily conserved eukaryotic processes. Ankyrin B (AnkB of L. pneumophila is a non-canonical F-box-containing protein, and is the only known Dot/Icm-translocated effector of L. pneumophila essential for intra-vacuolar proliferation within both macrophages and protozoan hosts. We show that the F-box domain of AnkB and the (9L(10P conserved residues are essential for intracellular bacterial proliferation and for rapid acquisition of polyubiquitinated proteins by the Legionella-containing vacuole (LCV within macrophages, Dictyostelium discoideum, and Acanthamoeba. Interestingly, translocation of AnkB and recruitment of polyubiquitinated proteins in macrophages and Acanthamoeba is rapidly triggered by extracellular bacteria within 5 min of bacterial attachment. Ectopically expressed AnkB within mammalian cells is localized to the periphery of the cell where it co-localizes with host SKP1 and recruits polyubiquitinated proteins, which results in restoration of intracellular growth to the ankB mutant similar to the parental strain. While an ectopically expressed AnkB-(9L(10P/AA variant is localized to the cell periphery, it does not recruit polyubiquitinated proteins and fails to trans-rescue the ankB mutant intracellular growth defect. Direct in vivo interaction of AnkB but not the AnkB-(9L(10P/AA variant with the host SKP1 is demonstrated. Importantly, RNAi-mediated silencing of expression of SKP1 renders the cells non-permissive for intracellular proliferation of L. pneumophila. The role of AnkB in exploitation of the polyubiquitination machinery is essential for intrapulmonary bacterial proliferation in the mouse model of Legionnaires' disease. Therefore, AnkB exhibits a novel molecular and functional mimicry of eukaryotic F-box proteins that exploits

  2. Adenylyl cyclase-5 in the dorsal striatum function as a molecular switch for the generation of behavioral preferences for cue-directed food choices.

    Science.gov (United States)

    Kim, Hannah; Kim, Tae-Kyung; Kim, Ji-Eun; Park, Jin-Young; Lee, Yunjin; Kang, Minkyung; Kim, Kyoung-Shim; Han, Pyung-Lim

    2014-11-07

    that the preferred food choices were switched on when either the mGluR3-AC5 pathway was inactive or the mGluR1 pathway was active, whereas the preferred food-choices were switched off when mGluR1 or its downstream pathway was suppressed. These results identify the AC5 and mGluR system in the dorsal striatum as molecular on/off switches to direct decisions on behavioral preferences for cue-oriented options.

  3. Phylogeny and molecular signatures (conserved proteins and indels that are specific for the Bacteroidetes and Chlorobi species

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    Lorenzini Emily

    2007-05-01

    Full Text Available Abstract Background The Bacteroidetes and Chlorobi species constitute two main groups of the Bacteria that are closely related in phylogenetic trees. The Bacteroidetes species are widely distributed and include many important periodontal pathogens. In contrast, all Chlorobi are anoxygenic obligate photoautotrophs. Very few (or no biochemical or molecular characteristics are known that are distinctive characteristics of these bacteria, or are commonly shared by them. Results Systematic blast searches were performed on each open reading frame in the genomes of Porphyromonas gingivalis W83, Bacteroides fragilis YCH46, B. thetaiotaomicron VPI-5482, Gramella forsetii KT0803, Chlorobium luteolum (formerly Pelodictyon luteolum DSM 273 and Chlorobaculum tepidum (formerly Chlorobium tepidum TLS to search for proteins that are uniquely present in either all or certain subgroups of Bacteroidetes and Chlorobi. These studies have identified > 600 proteins for which homologues are not found in other organisms. This includes 27 and 51 proteins that are specific for most of the sequenced Bacteroidetes and Chlorobi genomes, respectively; 52 and 38 proteins that are limited to species from the Bacteroidales and Flavobacteriales orders, respectively, and 5 proteins that are common to species from these two orders; 185 proteins that are specific for the Bacteroides genus. Additionally, 6 proteins that are uniquely shared by species from the Bacteroidetes and Chlorobi phyla (one of them also present in the Fibrobacteres have also been identified. This work also describes two large conserved inserts in DNA polymerase III (DnaE and alanyl-tRNA synthetase that are distinctive characteristics of the Chlorobi species and a 3 aa deletion in ClpB chaperone that is mainly found in various Bacteroidales, Flavobacteriales and Flexebacteraceae, but generally not found in the homologs from other organisms. Phylogenetic analyses of the Bacteroidetes and Chlorobi species is also

  4. Comparative Developmental Transcriptomics Reveals Rewiring of a Highly Conserved Gene Regulatory Network during a Major Life History Switch in the Sea Urchin Genus Heliocidaris.

    Science.gov (United States)

    Israel, Jennifer W; Martik, Megan L; Byrne, Maria; Raff, Elizabeth C; Raff, Rudolf A; McClay, David R; Wray, Gregory A

    2016-03-01

    The ecologically significant shift in developmental strategy from planktotrophic (feeding) to lecithotrophic (nonfeeding) development in the sea urchin genus Heliocidaris is one of the most comprehensively studied life history transitions in any animal. Although the evolution of lecithotrophy involved substantial changes to larval development and morphology, it is not known to what extent changes in gene expression underlie the developmental differences between species, nor do we understand how these changes evolved within the context of the well-defined gene regulatory network (GRN) underlying sea urchin development. To address these questions, we used RNA-seq to measure expression dynamics across development in three species: the lecithotroph Heliocidaris erythrogramma, the closely related planktotroph H. tuberculata, and an outgroup planktotroph Lytechinus variegatus. Using well-established statistical methods, we developed a novel framework for identifying, quantifying, and polarizing evolutionary changes in gene expression profiles across the transcriptome and within the GRN. We found that major changes in gene expression profiles were more numerous during the evolution of lecithotrophy than during the persistence of planktotrophy, and that genes with derived expression profiles in the lecithotroph displayed specific characteristics as a group that are consistent with the dramatically altered developmental program in this species. Compared to the transcriptome, changes in gene expression profiles within the GRN were even more pronounced in the lecithotroph. We found evidence for conservation and likely divergence of particular GRN regulatory interactions in the lecithotroph, as well as significant changes in the expression of genes with known roles in larval skeletogenesis. We further use coexpression analysis to identify genes of unknown function that may contribute to both conserved and derived developmental traits between species. Collectively, our results

  5. Molecular phylogeny of the genus Saguinus (Platyrrhini, Primates based on the ND1 mitochondrial gene and implications for conservation

    Directory of Open Access Journals (Sweden)

    Claudia Helena Tagliaro

    2005-03-01

    Full Text Available The systematics of the subfamily Callitrichinae (Platyrrhini, Primates, a group of small monkeys from South America and Panama, remains an area of considerable discussion despite many investigations, there being continuing controversy over subgeneric taxonomic classifications based on morphological characters. The purpose of our research was to help elucidate the phylogenetic relationships within the monkey genus Saguinus (Callitrichinae using a molecular approach to discover whether or not the two different sections containing hairy-faced and bare-faced species are monophyletic, whether Saguinus midas midas and Saguinus bicolor are more closely related than are S. midas midas and Saguinus midas niger, and if Saguinus fuscicollis melanoleucus and Saguinus fuscicollis weddelli really are different species. We sequenced the 957 bp ND1 mitochondrial gene of 21 Saguinus monkeys (belonging to six species and nine morphotypes and one Cebus monkey (the outgroup and constructed phylogenetic trees using maximum parsimony, neighbor joining, and maximum likelihood methods. The phylogenetic trees obtained divided the genus Saguinus into two groups, one containing the small-bodied species S. fuscicollis and the other, the large-bodied species S. mystax, S. leucopus, S. oedipus, S. midas, S. bicolor. The most derived taxa, S. midas and S. bicolor, grouped together, while S. fuscicollis melanoleucus and S. f. weddelli showed divergence values that did not support the division of these morphotypes into subspecies. On the other hand, S. midas individuals showed divergence compatible with the existence of three subspecies, two of them with the same morphotype as the subspecies S. midas niger. The results of our study suggest that there is at least one Saguinus subspecies that has not yet been described and that the conservation status of Saguinus species and subspecies should be carefully revised using modern molecular approaches.

  6. Discovery of molecular switches within the ADX-47273 mGlu5 PAM scaffold that modulate modes of pharmacology to afford potent mGlu5 NAMs, PAMs and partial antagonists.

    Science.gov (United States)

    Lamb, Jeffrey P; Engers, Darren W; Niswender, Colleen M; Rodriguez, Alice L; Venable, Daryl F; Conn, P Jeffrey; Lindsley, Craig W

    2011-05-01

    This Letter describes a chemical lead optimization campaign directed at a weak mGlu(5) NAM discovered while developing SAR for the mGlu(5) PAM, ADX-47273. An iterative parallel synthesis effort discovered multiple, subtle molecular switches that afford potent mGlu(5) NAMs, mGlu(5) PAMs as well as mGlu(5) partial antagonists.

  7. Molecular dynamics studies unravel role of conserved residues responsible for movement of ions into active site of DHBPS

    Science.gov (United States)

    Shinde, Ranajit Nivrutti; Karthikeyan, Subramanian; Singh, Balvinder

    2017-01-01

    3,4-dihydroxy-2-butanone-4-phosphate synthase (DHBPS) catalyzes the conversion of D-ribulose 5-phosphate (Ru5P) to L-3,4-dihydroxy-2-butanone-4-phosphate in the presence of Mg2+. Although crystal structures of DHBPS in complex with Ru5P and non-catalytic metal ions have been reported, structure with Ru5P along with Mg2+ is still elusive. Therefore, mechanistic role played by Mg2+ in the structure of DHBPS is poorly understood. In this study, molecular dynamics simulations of DHBPS-Ru5P complex along with Mg2+ have shown entry of Mg2+ from bulk solvent into active site. Presence of Mg2+ in active site has constrained conformations of Ru5P and has reduced flexibility of loop-2. Formation of hydrogen bonds among Thr-108 and residues - Gly-109, Val-110, Ser-111, and Asp-114 are found to be critical for entry of Mg2+ into active site. Subsequent in silico mutations of residues, Thr-108 and Asp-114 have substantiated the importance of these interactions. Loop-4 of one monomer is being proposed to act as a “lid” covering the active site of other monomer. Further, the conserved nature of residues taking part in the transfer of Mg2+ suggests the same mechanism being present in DHBPS of other microorganisms. Thus, this study provides insights into the functioning of DHBPS that can be used for the designing of inhibitors.

  8. Hybrid MPI/OpenMP Implementation of the ORAC Molecular Dynamics Program for Generalized Ensemble and Fast Switching Alchemical Simulations.

    Science.gov (United States)

    Procacci, Piero

    2016-06-27

    We present a new release (6.0β) of the ORAC program [Marsili et al. J. Comput. Chem. 2010, 31, 1106-1116] with a hybrid OpenMP/MPI (open multiprocessing message passing interface) multilevel parallelism tailored for generalized ensemble (GE) and fast switching double annihilation (FS-DAM) nonequilibrium technology aimed at evaluating the binding free energy in drug-receptor system on high performance computing platforms. The production of the GE or FS-DAM trajectories is handled using a weak scaling parallel approach on the MPI level only, while a strong scaling force decomposition scheme is implemented for intranode computations with shared memory access at the OpenMP level. The efficiency, simplicity, and inherent parallel nature of the ORAC implementation of the FS-DAM algorithm, project the code as a possible effective tool for a second generation high throughput virtual screening in drug discovery and design. The code, along with documentation, testing, and ancillary tools, is distributed under the provisions of the General Public License and can be freely downloaded at www.chim.unifi.it/orac .

  9. Phosphorylation state of CREB in the rat hippocampus: a molecular switch between spatial novelty and spatial familiarity?

    Science.gov (United States)

    Moncada, Diego; Viola, Haydée

    2006-07-01

    The activation of cAMP response element-binding protein (CREB) after a learning experience is a common feature in the formation of several associative memories. We recently demonstrated that the increase in the hippocampal phosphorylated CREB (pCREB) levels 1 h after a short exploration of an open field (OF) was associated to detection of spatial novelty and was not related to the memory formation of habituation in this non-associative learning paradigm. Moreover, after a long training of three OF sessions, hippocampal pCREB levels were below to that observed in control rats. The present results show that such decrease does not correlate with memory retrieval or improvement in long-term memory of habituation. Instead, it is associated with the familiarity to the arena. Our experiments revealed that the relevant variable to induce CREB deactivation was the prolonged exploration of the arena (30 min). A 15 min OF exploration was ineffective. Furthermore, the last 5 min period of a prolonged exploration was crucial to change CREB phosphorylation state: when exploration took place in a novel arena the level of pCREB increased; in contrast, when it was performed in the familiar OF, pCREB levels decreased. Taken as a whole, our results suggest that CREB phosphorylation state in the hippocampus switches in response to exposure to a novel or to a familiar spatial environment.

  10. Femtosecond Laser Spectroscopy of the Rhodopsin Photochromic Reaction: A Concept for Ultrafast Optical Molecular Switch Creation (Ultrafast Reversible Photoreaction of Rhodopsin

    Directory of Open Access Journals (Sweden)

    Olga Smitienko

    2014-11-01

    Full Text Available Ultrafast reverse photoreaction of visual pigment rhodopsin in the femtosecond time range at room temperature is demonstrated. Femtosecond two-pump probe experiments with a time resolution of 25 fs have been performed. The first рump pulse at 500 nm initiated cis-trans photoisomerization of rhodopsin chromophore, 11-cis retinal, which resulted in the formation of the primary ground-state photoproduct within a mere 200 fs. The second pump pulse at 620 nm with a varying delay of 200 to 3750 fs relative to the first рump pulse, initiated the reverse phototransition of the primary photoproduct to rhodopsin. The results of this photoconversion have been observed on the differential spectra obtained after the action of two pump pulses at a time delay of 100 ps. It was found that optical density decreased at 560 nm in the spectral region of bathorhodopsin absorption and increased at 480 nm, where rhodopsin absorbs. Rhodopsin photoswitching efficiency shows oscillations as a function of the time delay between two рump pulses. The quantum yield of reverse photoreaction initiated by the second pump pulse falls within the range 15% ± 1%. The molecular mechanism of the ultrafast reversible photoreaction of visual pigment rhodopsin may be used as a concept for the development of an ultrafast optical molecular switch.

  11. Photoinduced switching to metallic states in the two-dimensional organic Mott insulator dimethylphenazine-tetrafluorotetracyanoquinodimethane with anisotropic molecular stacks

    Science.gov (United States)

    Matsuzaki, Hiroyuki; Ohkura, Masa-aki; Ishige, Yu; Nogami, Yoshio; Okamoto, Hiroshi

    2015-06-01

    A photoinduced phase transition was investigated in an organic charge-transfer (CT) complex M2P -TCNQ F4 , [M2P : 5,10-dihydro-5,10-dimethylphenazine, donor (D) molecule; TCNQ F4 : 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane, acceptor (A) molecule] by means of femtosecond pump-probe reflection spectroscopy. This is an ionic compound and has a peculiar two-dimensional (2D) molecular arrangement; the same A (or D) molecules arrange along the [100] direction, and A and D molecules alternately arrange along the [111] direction. It results in a strongly anisotropic two-dimensional electronic structure. This compound shows a structural and magnetic phase transition at 122 K below which the two neighboring molecules are dimerized along both the [100] and [111] directions. We demonstrate that two kinds of photoinduced phase transitions occur by irradiation of a femtosecond laser pulse; in the high-temperature lattice-uniform phase, a quasi-one-dimensional (1D) metallic state along the AA(DD) stack is generated, and in the low-temperature lattice-dimerized phase, a quasi-2D metallic state is initially produced and molecular dimerizations are subsequently released. Mixed-stack CT compounds consisting of DA stacks are generally insulators or semiconductors in the ground state. Here, such a dynamical metallization in the DA stack is demonstrated. The release of the dimerizations drives several kinds of coherent oscillations which play an important role in the stabilization of the lattice-dimerized phase. The mechanisms of those photoinduced phase transitions are discussed in terms of the magnitudes of the anisotropic bandwidths and molecular dimerizations along two different directions of the molecular stacks.

  12. Role of accelerated segment switch in exons to alter targeting (ASSET in the molecular evolution of snake venom proteins

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    Kini R Manjunatha

    2009-06-01

    Full Text Available Abstract Background Snake venom toxins evolve more rapidly than other proteins through accelerated changes in the protein coding regions. Previously we have shown that accelerated segment switch in exons to alter targeting (ASSET might play an important role in its functional evolution of viperid three-finger toxins. In this phenomenon, short sequences in exons are radically changed to unrelated sequences and hence affect the folding and functional properties of the toxins. Results Here we analyzed other snake venom protein families to elucidate the role of ASSET in their functional evolution. ASSET appears to be involved in the functional evolution of three-finger toxins to a greater extent than in several other venom protein families. ASSET leads to replacement of some of the critical amino acid residues that affect the biological function in three-finger toxins as well as change the conformation of the loop that is involved in binding to specific target sites. Conclusion ASSET could lead to novel functions in snake venom proteins. Among snake venom serine proteases, ASSET contributes to changes in three surface segments. One of these segments near the substrate binding region is known to affect substrate specificity, and its exchange may have significant implications for differences in isoform catalytic activity on specific target protein substrates. ASSET therefore plays an important role in functional diversification of snake venom proteins, in addition to accelerated point mutations in the protein coding regions. Accelerated point mutations lead to fine-tuning of target specificity, whereas ASSET leads to large-scale replacement of multiple functionally important residues, resulting in change or gain of functions.

  13. Conserved Molecular Superlattices in a Series of Homologous Synthetic Mycobacterial Cell-Wall Lipids Forming Interdigitated Bilayers.

    Science.gov (United States)

    Martin-Bertelsen, Birte; Yaghmur, Anan; Franzyk, Henrik; Justesen, Sarah; Kirkensgaard, Jacob J K; Foged, Camilla

    2016-12-06

    Synthetic analogues of the cell-wall lipid monomycoloyl glycerol (MMG) are promising as next-generation vaccine adjuvants. In the present study, the thermotropic phase behavior of an array of synthetic MMG analogues was examined by using simultaneous small- and wide-angle X-ray scattering under excess water conditions. The MMG analogues differed in the alkyl chain lengths and in the stereochemistry of the polar glycerol headgroup or of the lipid tails (native-like versus alternative compounds). All MMG analogues formed poorly hydrated lamellar phases at low temperatures and inverse hexagonal (H2) phases at higher temperatures prior to melting. MMG analogues with a native-like lipid acid configuration self-assembled into noninterdigitated bilayers whereas the analogues displaying an alternative lipid acid configuration formed interdigitated bilayers in a subgel (Lc') state. This is in contrast to previously described interdigitated phases for other lipids, which are usually in a gel (Lβ) state. All investigated MMG analogues displayed an abrupt direct temperature-induced phase transition from Lc' to H2. This transition is ultimately driven by the lipid chain melting and the accompanying change in molecular shape. No intermediate structures were found, but the entire array of MMG analogues displayed phase coexistence during the lamellar to H2 transition. The structural data also showed that the headgroups of the MMG analogues adopting the alternative lipid acid configuration were ordered and formed a two-dimensional molecular superlattice, which was conserved regardless of the lipid tail length. To our knowledge, the MMG analogues with an alternative lipid acid configuration represent the first example of a lipid system showing both interdigitation and superlattice formation, and as such could serve as an interesting model system for future studies. The MMG analogues are also relevant from a subunit vaccine perspective because they are well-tolerated and display

  14. Conserved cis-regulatory modules in promoters of genes encoding wheat high-molecular-weight glutenin subunits.

    Science.gov (United States)

    Ravel, Catherine; Fiquet, Samuel; Boudet, Julie; Dardevet, Mireille; Vincent, Jonathan; Merlino, Marielle; Michard, Robin; Martre, Pierre

    2014-01-01

    The concentration and composition of the gliadin and glutenin seed storage proteins (SSPs) in wheat flour are the most important determinants of its end-use value. In cereals, the synthesis of SSPs is predominantly regulated at the transcriptional level by a complex network involving at least five cis-elements in gene promoters. The high-molecular-weight glutenin subunits (HMW-GS) are encoded by two tightly linked genes located on the long arms of group 1 chromosomes. Here, we sequenced and annotated the HMW-GS gene promoters of 22 electrophoretic wheat alleles to identify putative cis-regulatory motifs. We focused on 24 motifs known to be involved in SSP gene regulation. Most of them were identified in at least one HMW-GS gene promoter sequence. A common regulatory framework was observed in all the HMW-GS gene promoters, as they shared conserved cis-regulatory modules (CCRMs) including all the five motifs known to regulate the transcription of SSP genes. This common regulatory framework comprises a composite box made of the GATA motifs and GCN4-like Motifs (GLMs) and was shown to be functional as the GLMs are able to bind a bZIP transcriptional factor SPA (Storage Protein Activator). In addition to this regulatory framework, each HMW-GS gene promoter had additional motifs organized differently. The promoters of most highly expressed x-type HMW-GS genes contain an additional box predicted to bind R2R3-MYB transcriptional factors. However, the differences in annotation between promoter alleles could not be related to their level of expression. In summary, we identified a common modular organization of HMW-GS gene promoters but the lack of correlation between the cis-motifs of each HMW-GS gene promoter and their level of expression suggests that other cis-elements or other mechanisms regulate HMW-GS gene expression.

  15. Insights into the molecular evolution of the PDZ/LIM family and identification of a novel conserved protein motif.

    Directory of Open Access Journals (Sweden)

    Aartjan J W Te Velthuis

    Full Text Available The PDZ and LIM domain-containing protein family is encoded by a diverse group of genes whose phylogeny has currently not been analyzed. In mammals, ten genes are found that encode both a PDZ- and one or several LIM-domains. These genes are: ALP, RIL, Elfin (CLP36, Mystique, Enigma (LMP-1, Enigma homologue (ENH, ZASP (Cypher, Oracle, LMO7 and the two LIM domain kinases (LIMK1 and LIMK2. As conventional alignment and phylogenetic procedures of full-length sequences fell short of elucidating the evolutionary history of these genes, we started to analyze the PDZ and LIM domain sequences themselves. Using information from most sequenced eukaryotic lineages, our phylogenetic analysis is based on full-length cDNA-, EST-derived- and genomic- PDZ and LIM domain sequences of over 25 species, ranging from yeast to humans. Plant and protozoan homologs were not found. Our phylogenetic analysis identifies a number of domain duplication and rearrangement events, and shows a single convergent event during evolution of the PDZ/LIM family. Further, we describe the separation of the ALP and Enigma subfamilies in lower vertebrates and identify a novel consensus motif, which we call 'ALP-like motif' (AM. This motif is highly-conserved between ALP subfamily proteins of diverse organisms. We used here a combinatorial approach to define the relation of the PDZ and LIM domain encoding genes and to reconstruct their phylogeny. This analysis allowed us to classify the PDZ/LIM family and to suggest a meaningful model for the molecular evolution of the diverse gene architectures found in this multi-domain family.

  16. Tuning the temperature dependence for switching in dithienylethene photochromic switches.

    Science.gov (United States)

    Kudernac, Tibor; Kobayashi, Takao; Uyama, Ayaka; Uchida, Kingo; Nakamura, Shinichiro; Feringa, Ben L

    2013-08-29

    Diarylethene photochromic switches use light to drive structural changes through reversible electrocyclization reactions. High efficiency in dynamic photoswitching is a prerequisite for applications, as is thermal stability and the selective addressability of both isomers ring-opened and -closed diarylethenes. These properties can be optimized readily through rational variation in molecular structure. The efficiency with regard to switching as a function of structural variation is much less understood, with the exception of geometric requirements placed on the reacting atoms. Ultimately, increasing the quantum efficiency of photochemical switching in diarylethenes requires a detailed understanding of the excited-state potential energy surface(s) and the mechanisms involved in switching. Through studies of the temperature dependence, photoswitching and theoretical studies demonstrate the occurrence or absence of thermal activation barriers in three constitutional isomers that bear distinct π-conjugated systems. We found that a decrease in the thermal barriers correlates with an increase in switching efficiency. The origin of the barriers is assigned to the decrease in π-conjugation that is concomitant with the progress of the photoreaction. Furthermore, we show that balanced molecular design can minimize the change in the extent of π-conjugation during switching and lead to optimal bidirectional switching efficiencies. Our findings hold implications for future structural design of diarylethene photochromic switches.

  17. Discovery of a regioselectivity switch in nitrating P450s guided by molecular dynamics simulations and Markov models

    Science.gov (United States)

    Dodani, Sheel C.; Kiss, Gert; Cahn, Jackson K. B.; Su, Ye; Pande, Vijay S.; Arnold, Frances H.

    2016-05-01

    The dynamic motions of protein structural elements, particularly flexible loops, are intimately linked with diverse aspects of enzyme catalysis. Engineering of these loop regions can alter protein stability, substrate binding and even dramatically impact enzyme function. When these flexible regions are unresolvable structurally, computational reconstruction in combination with large-scale molecular dynamics simulations can be used to guide the engineering strategy. Here we present a collaborative approach that consists of both experiment and computation and led to the discovery of a single mutation in the F/G loop of the nitrating cytochrome P450 TxtE that simultaneously controls loop dynamics and completely shifts the enzyme's regioselectivity from the C4 to the C5 position of L-tryptophan. Furthermore, we find that this loop mutation is naturally present in a subset of homologous nitrating P450s and confirm that these uncharacterized enzymes exclusively produce 5-nitro-L-tryptophan, a previously unknown biosynthetic intermediate.

  18. Control and manipulation of quantum spin switching and spin correlations in [Tb2] molecular magnet under a pulse magnetic field

    Science.gov (United States)

    Farberovich, Oleg V.; Bazhanov, Dmitry I.

    2017-10-01

    A general study of [Tb2] molecular magnet is presented using the general spin Hamiltonian formalism. A spin-spin correlators determined for a spin wave functions in [Tb2] are analyzed numerically and compared in details with the results obtained by means of conventional quantum mechanics. It is shown that the various expectation values of the spin operators and a study of their corresponding probability distributions allow to have a novel understanding in spin dynamics of entangled qubits in quantum [Tb2] system. The obtained results reveal that the properties of spin-spin correlators are responsible for the entanglement of the spin qubit under a pulse magnetic field. It allows us to present some quantum circuits determined for quantum computing within SSNQ based on [Tb2] molecule, including the CNOT and SWAP gates.

  19. Nucleosome switches.

    Science.gov (United States)

    Schwab, David J; Bruinsma, Robijn F; Rudnick, Joseph; Widom, Jonathan

    2008-06-06

    We present a statistical-mechanical model for the positioning of nucleosomes along genomic DNA molecules as a function of the strength of the binding potential and the chemical potential of the nucleosomes. We show that a significant section of the DNA is composed of two-level nucleosome switching regions where the nucleosome distribution undergoes a localized, first-order transition. The location of the nucleosome switches shows a strong correlation with the location of gene-regulation regions.

  20. Bottom-up derivation of conservative and dissipative interactions for coarse-grained molecular liquids with the conditional reversible work method

    Energy Technology Data Exchange (ETDEWEB)

    Deichmann, Gregor; Marcon, Valentina; Vegt, Nico F. A. van der, E-mail: vandervegt@csi.tu-darmstadt.de [Center of Smart Interfaces, Technische Universität Darmstadt, Alarich-Weiss-Straße 10, 64287 Darmstadt (Germany)

    2014-12-14

    Molecular simulations of soft matter systems have been performed in recent years using a variety of systematically coarse-grained models. With these models, structural or thermodynamic properties can be quite accurately represented while the prediction of dynamic properties remains difficult, especially for multi-component systems. In this work, we use constraint molecular dynamics simulations for calculating dissipative pair forces which are used together with conditional reversible work (CRW) conservative forces in dissipative particle dynamics (DPD) simulations. The combined CRW-DPD approach aims to extend the representability of CRW models to dynamic properties and uses a bottom-up approach. Dissipative pair forces are derived from fluctuations of the direct atomistic forces between mapped groups. The conservative CRW potential is obtained from a similar series of constraint dynamics simulations and represents the reversible work performed to couple the direct atomistic interactions between the mapped atom groups. Neopentane, tetrachloromethane, cyclohexane, and n-hexane have been considered as model systems. These molecular liquids are simulated with atomistic molecular dynamics, coarse-grained molecular dynamics, and DPD. We find that the CRW-DPD models reproduce the liquid structure and diffusive dynamics of the liquid systems in reasonable agreement with the atomistic models when using single-site mapping schemes with beads containing five or six heavy atoms. For a two-site representation of n-hexane (3 carbons per bead), time scale separation can no longer be assumed and the DPD approach consequently fails to reproduce the atomistic dynamics.

  1. A rapid drug release system with a NIR light-activated molecular switch for dual-modality photothermal/antibiotic treatments of subcutaneous abscesses.

    Science.gov (United States)

    Chiang, Wei-Lun; Lin, Tzu-Tsen; Sureshbabu, Radhakrishnan; Chia, Wei-Tso; Hsiao, Hsu-Chan; Liu, Hung-Yi; Yang, Chih-Man; Sung, Hsing-Wen

    2015-02-10

    Eradicating subcutaneous bacterial infections remains a significant challenge. This work reports an injectable system of hollow microspheres (HMs) that can rapidly produce localized heat activated by near-infrared (NIR) light and control the release of an antibiotic via a "molecular switch" in their polymer shells, as a combination strategy for treating subcutaneous abscesses. The HMs have a shell of poly(d,l-lactic-co-glycolic acid) (PLGA) and an aqueous core that is comprised of vancomycin (Van) and polypyrrole nanoparticles (PPy NPs), which are photothermal agents. Experimental results demonstrate that the micro-HMs ensure efficiently the spatial stabilization of their encapsulated Van and PPy NPs at the injection site in mice with subcutaneous abscesses. Without NIR irradiation, the HMs elute a negligible drug concentration, but release substantially more when exposed to NIR light, suggesting that this system is suitable as a photothermally-responsive drug delivery system. The combination of photothermally-induced hyperthermia and antibiotic therapy with HMs increases cytotoxicity for bacteria in abscesses, to an extent that is greater than the sum of the two treatments alone, demonstrating a synergistic effect. This treatment platform may find other clinical applications, especially for localized hyperthermia-based cancer therapy.

  2. Cellular Dichotomy Between Anchorage-Independent Growth Responses to bFGF and TA Reflects Molecular Switch in Commitment to Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Waters, Katrina M.; Tan, Ruimin; Opresko, Lee K.; Quesenberry, Ryan D.; Bandyopadhyay, Somnath; Chrisler, William B.; Weber, Thomas J.

    2009-11-01

    We have investigated gene expression patterns underlying reversible and irreversible anchorage-independent growth (AIG) phenotypes to identify more sensitive markers of cell transformation for studies directed at interrogating carcinogenesis responses. In JB6 mouse epidermal cells, basic fibroblast growth factor (bFGF) induces an unusually efficient and reversible AIG response, relative to 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced AIG which is irreversible. The reversible and irreversible AIG phenotypes are characterized by largely non-overlapping global gene expression profiles. However, a subset of differentially expressed genes were identified as common to reversible and irreversible AIG phenotypes, including genes regulated in a reciprocal fashion. Hepatic leukemia factor (HLF) and D-site albumin promoter-binding protein (DBP) were increased in both bFGF and TPA soft agar colonies and selected for functional validation. Ectopic expression of human HLF and DBP in JB6 cells resulted in a marked increase in TPA- and bFGF-regulated AIG responses. HLF and DBP expression were increased in soft agar colonies arising from JB6 cells exposed to gamma radiation and in a human basal cell carcinoma tumor tissue, relative to paired non-tumor tissue. Subsequent biological network analysis suggests that many of the differentially expressed genes that are common to bFGF- and TPA-dependent AIG are regulated by c-Myc, SP-1 and HNF-4 transcription factors. Collectively, we have identified a potential molecular switch that mediates the transition from reversible to irreversible AIG.

  3. Glucosidase II β-subunit, a novel substrate for caspase-3-like activity in rice, plays as a molecular switch between autophagy and programmed cell death

    Science.gov (United States)

    Cui, Jing; Chen, Bing; Wang, Hongjuan; Han, Yue; Chen, Xi; Zhang, Wei

    2016-01-01

    Endoplasmic reticulum (ER) stress activates unfolded protein response (UPR) and autophagy. However, prolonged, severe stresses activate programmed cell death (PCD) in both animal and plant cells. Compared to the well-studied UPR pathway, the molecular mechanisms of ER-stress-induced PCD are less understood. Here, we report the identification of Gas2, the glucosidase II β subunit in the ER, as a potential switch between PCD and autophagy in rice. MS analysis identified Gas2, GRP94, and HSP40 protein in a purified caspase-3-like activity from heat stressed rice cell suspensions. The three corresponding genes were down-regulated under DTT-induced ER stress. Gas2 and GRP94 were localized to the ER, while HSP40 localized to the cytoplasm. Compared to wild-type, a Gas2 RNAi cell line was much sensitive to DTT treatment and had high levels of autophagy. Both caspase-3 and heat-stressed cell suspension lysate could cleave Gas2, producing a 14 kDa N-terminal fragment. Conditional expression of corresponding C-terminal fragment resulted in enhanced caspase-3-like activity in the protoplasts under heat stress. We proposed that mild ER stress causes down-regulation of Gas2 and induces autophagy, while severe stress results in Gas2 cleavage by caspase-3-like activity and the cleavage product amplifies this activity, possibly participating in the initiation of PCD. PMID:27538481

  4. Molecular switch role of Akt in Polygonatum odoratum lectin-induced apoptosis and autophagy in human non-small cell lung cancer A549 cells.

    Science.gov (United States)

    Li, Chunyang; Chen, Jie; Lu, Bangmin; Shi, Zheng; Wang, Hailian; Zhang, Bin; Zhao, Kailiang; Qi, Wei; Bao, Jinku; Wang, Yi

    2014-01-01

    Polygonatum odoratum lectin (POL), isolated from traditional Chinese medicine herb (Mill.) Druce, has drawn rising attention due to its wide biological activities. In the present study, anti-tumor effects, including apoptosis- and autophagy-inducing properties of POL, were determined by a series of cell biology methods such as MTT, cellular morphology observation, flow cytometry, immunoblotting. Herein, we found that POL could simultaneously induce apoptosis and autophagy in human non-small cell lung cancer A549 cells. POL initiated apoptosis through inhibiting Akt-NF-κB pathway, while POL triggered autophagy via suppressing Akt-mTOR pathway, suggesting the molecular switch role of Akt in regulating between POL-induced apoptosis and autophagy. Moreover, ROS was involved in POL-induced inhibition of Akt expression, and might therefore mediate both apoptosis and autophagy in A549 cells. In addition, POL displayed no significant cytotoxicity toward normal human embryonic lung fibroblast HELF cells. Due to the anti-tumor activities, POL might become a potent anti-cancer drug in future therapy, which might pave the way for exploring GNA-related lectins into effective drugs in cancer treatment.

  5. Enterovirus 71 binding to PSGL-1 on leukocytes: VP1-145 acts as a molecular switch to control receptor interaction.

    Directory of Open Access Journals (Sweden)

    Yorihiro Nishimura

    Full Text Available Some strains of enterovirus 71 (EV71, but not others, infect leukocytes by binding to a specific receptor molecule: the P-selectin glycoprotein ligand-1 (PSGL-1. We find that a single amino acid residue within the capsid protein VP1 determines whether EV71 binds to PSGL-1. Examination of capsid sequences of representative EV71 strains revealed that the PSGL-1-binding viruses had either a G or a Q at residue 145 within the capsid protein VP1 (VP1-145G or Q, whereas PSGL-1-nonbinding viruses had VP1-145E. Using site-directed mutagenesis we found that PSGL-1-binding strains lost their capacity to bind when VP1-145G/Q was replaced by E; conversely, nonbinding strains gained the capacity to bind PSGL-1 when VP1-145E was replaced with either G or Q. Viruses with G/Q at VP1-145 productively infected a leukocyte cell line, Jurkat T-cells, whereas viruses with E at this position did not. We previously reported that EV71 binds to the N-terminal region of PSGL-1, and that binding depends on sulfated tyrosine residues within this region. We speculated that binding depends on interaction between negatively charged sulfate groups and positively charged basic residues in the virus capsid. VP1-145 on the virus surface is in close proximity to conserved lysine residues at VP1-242 and VP1-244. Comparison of recently published crystal structures of EV71 isolates with either Q or E at VP1-145 revealed that VP1-145 controls the orientation of the lysine side-chain of VP1-244: with VP1-145Q the lysine side chain faces outward, but with VP1-145E, the lysine side chain is turned toward the virus surface. Mutation of VP1-244 abolished virus binding to PSGL-1, and mutation of VP1-242 greatly reduced binding. We propose that conserved lysine residues on the virus surface are responsible for interaction with sulfated tyrosine residues at the PSGL-1 N-terminus, and that VP1-145 acts as a switch, controlling PSGL-1 binding by modulating the exposure of VP1-244K.

  6. Enterovirus 71 binding to PSGL-1 on leukocytes: VP1-145 acts as a molecular switch to control receptor interaction.

    Science.gov (United States)

    Nishimura, Yorihiro; Lee, Hyunwook; Hafenstein, Susan; Kataoka, Chikako; Wakita, Takaji; Bergelson, Jeffrey M; Shimizu, Hiroyuki

    2013-01-01

    Some strains of enterovirus 71 (EV71), but not others, infect leukocytes by binding to a specific receptor molecule: the P-selectin glycoprotein ligand-1 (PSGL-1). We find that a single amino acid residue within the capsid protein VP1 determines whether EV71 binds to PSGL-1. Examination of capsid sequences of representative EV71 strains revealed that the PSGL-1-binding viruses had either a G or a Q at residue 145 within the capsid protein VP1 (VP1-145G or Q), whereas PSGL-1-nonbinding viruses had VP1-145E. Using site-directed mutagenesis we found that PSGL-1-binding strains lost their capacity to bind when VP1-145G/Q was replaced by E; conversely, nonbinding strains gained the capacity to bind PSGL-1 when VP1-145E was replaced with either G or Q. Viruses with G/Q at VP1-145 productively infected a leukocyte cell line, Jurkat T-cells, whereas viruses with E at this position did not. We previously reported that EV71 binds to the N-terminal region of PSGL-1, and that binding depends on sulfated tyrosine residues within this region. We speculated that binding depends on interaction between negatively charged sulfate groups and positively charged basic residues in the virus capsid. VP1-145 on the virus surface is in close proximity to conserved lysine residues at VP1-242 and VP1-244. Comparison of recently published crystal structures of EV71 isolates with either Q or E at VP1-145 revealed that VP1-145 controls the orientation of the lysine side-chain of VP1-244: with VP1-145Q the lysine side chain faces outward, but with VP1-145E, the lysine side chain is turned toward the virus surface. Mutation of VP1-244 abolished virus binding to PSGL-1, and mutation of VP1-242 greatly reduced binding. We propose that conserved lysine residues on the virus surface are responsible for interaction with sulfated tyrosine residues at the PSGL-1 N-terminus, and that VP1-145 acts as a switch, controlling PSGL-1 binding by modulating the exposure of VP1-244K.

  7. SFC在分子筛纯化系统切换控制中的应用%Application of SFC in switching-over control of molecular sieve purification system

    Institute of Scientific and Technical Information of China (English)

    付定君; 伍晓娟; 徐平林

    2011-01-01

    针对分子筛纯化系统切换控制的特点,结合横河CETUMCS3000控制系统中的顺序控制功能,介绍了SFC在分子筛纯化系统切换控制中的应用,以及一些组态经验和维护措施。%Application of SFC in switching-over control of molecular sieve purification system is briefed on basis of the features of switching-over control of molecular sieve purification system in combination with function of sequence control of Henghe CETUM CS3000 control system and experiences on configuration and maintenance measures are described.

  8. Nucleotide binding switches the information flow in ras GTPases.

    Science.gov (United States)

    Raimondi, Francesco; Portella, Guillem; Orozco, Modesto; Fanelli, Francesca

    2011-03-01

    The Ras superfamily comprises many guanine nucleotide-binding proteins (G proteins) that are essential to intracellular signal transduction. The guanine nucleotide-dependent intrinsic flexibility patterns of five G proteins were investigated in atomic detail through Molecular Dynamics simulations of the GDP- and GTP-bound states (S(GDP) and S(GTP), respectively). For all the considered systems, the intrinsic flexibility of S(GDP) was higher than that of S(GTP), suggesting that Guanine Exchange Factor (GEF) recognition and nucleotide switch require higher amplitude motions than effector recognition or GTP hydrolysis. Functional mode, dynamic domain, and interaction energy correlation analyses highlighted significant differences in the dynamics of small G proteins and Gα proteins, especially in the inactive state. Indeed, S(GDP) of Gα(t), is characterized by a more extensive energy coupling between nucleotide binding site and distal regions involved in GEF recognition compared to small G proteins, which attenuates in the active state. Moreover, mechanically distinct domains implicated in nucleotide switch could be detected in the presence of GDP but not in the presence of GTP. Finally, in small G proteins, functional modes are more detectable in the inactive state than in the active one and involve changes in solvent exposure of two highly conserved amino acids in switches I and II involved in GEF recognition. The average solvent exposure of these amino acids correlates in turn with the rate of GDP release, suggesting for them either direct or indirect roles in the process of nucleotide switch. Collectively, nucleotide binding changes the information flow through the conserved Ras-like domain, where GDP enhances the flexibility of mechanically distinct portions involved in nucleotide switch, and favors long distance allosteric communication (in Gα proteins), compared to GTP.

  9. Nucleotide binding switches the information flow in ras GTPases.

    Directory of Open Access Journals (Sweden)

    Francesco Raimondi

    2011-03-01

    Full Text Available The Ras superfamily comprises many guanine nucleotide-binding proteins (G proteins that are essential to intracellular signal transduction. The guanine nucleotide-dependent intrinsic flexibility patterns of five G proteins were investigated in atomic detail through Molecular Dynamics simulations of the GDP- and GTP-bound states (S(GDP and S(GTP, respectively. For all the considered systems, the intrinsic flexibility of S(GDP was higher than that of S(GTP, suggesting that Guanine Exchange Factor (GEF recognition and nucleotide switch require higher amplitude motions than effector recognition or GTP hydrolysis. Functional mode, dynamic domain, and interaction energy correlation analyses highlighted significant differences in the dynamics of small G proteins and Gα proteins, especially in the inactive state. Indeed, S(GDP of Gα(t, is characterized by a more extensive energy coupling between nucleotide binding site and distal regions involved in GEF recognition compared to small G proteins, which attenuates in the active state. Moreover, mechanically distinct domains implicated in nucleotide switch could be detected in the presence of GDP but not in the presence of GTP. Finally, in small G proteins, functional modes are more detectable in the inactive state than in the active one and involve changes in solvent exposure of two highly conserved amino acids in switches I and II involved in GEF recognition. The average solvent exposure of these amino acids correlates in turn with the rate of GDP release, suggesting for them either direct or indirect roles in the process of nucleotide switch. Collectively, nucleotide binding changes the information flow through the conserved Ras-like domain, where GDP enhances the flexibility of mechanically distinct portions involved in nucleotide switch, and favors long distance allosteric communication (in Gα proteins, compared to GTP.

  10. The Molecular Switch of Telomere Phages: High Binding Specificity of the PY54 Cro Lytic Repressor to a Single Operator Site

    Directory of Open Access Journals (Sweden)

    Jens Andre Hammerl

    2015-06-01

    Full Text Available Temperate bacteriophages possess a molecular switch, which regulates the lytic and lysogenic growth. The genomes of the temperate telomere phages N15, PY54 and ɸKO2 harbor a primary immunity region (immB comprising genes for the prophage repressor, the lytic repressor and a putative antiterminator. The roles of these products are thought to be similar to those of the lambda proteins CI, Cro and Q, respectively. Moreover, the gene order and the location of several operator sites in the prototype telomere phage N15 and in ɸKO2 are also reminiscent of lambda-like phages. By contrast, in silico analyses revealed the presence of only one operator (O\\(_{\\rm{R}}\\3 in PY54. The purified PY54 Cro protein was used for EMSA studies demonstrating that it exclusively binds to a 16-bp palindromic site (O\\(_{\\rm{R}}\\3 upstream of the prophage repressor gene. The O\\(_{\\rm{R}}\\3 operator sequences of PY54 and ɸKO2/N15 only differ by their peripheral base pairs, which are responsible for Cro specificity. PY54 cI and cro transcription is regulated by highly active promoters initiating the synthesis of a homogenious species of leaderless mRNA. The location of the PY54 Cro binding site and of the identified promoters suggests that the lytic repressor suppresses cI transcription but not its own synthesis. The results indicate an unexpected diversity of the growth regulation mechanisms in lambda-related phages.

  11. Switching antidepressants

    African Journals Online (AJOL)

    by this time.4. Next-step ... and the side-effects are minimal), switching to an alternative antidepressant (if .... the new SSRI initiated immediately at the former therapeutic equivalent dose ... weeks because of the long half-life of its active metabolite, .... interactions with second-generation antidepressants: an update. Clin Ther.

  12. Sector Switching

    DEFF Research Database (Denmark)

    Newman, Carol; Rand, John; Tarp, Finn

    Much of the literature on industry evolution has found firm dynamics to be an important source of sector-level productivity growth. In this paper, we ask whether the delineation of entry and exit firms matters in assessing the impact of firm turnover. Using detailed firm level data from Vietnam......-level determinants of firm exit and switching, which need to be carefully considered in the search for effective policy...

  13. Sector Switching

    DEFF Research Database (Denmark)

    Newman, Carol; Rand, John; Tarp, Finn

    Much of the literature on industry evolution has found firm dynamics to be an important source of sector-level productivity growth. In this paper, we ask whether the delineation of entry and exit firms matters in assessing the impact of firm turnover. Using detailed firm level data from Vietnam, ......-level determinants of firm exit and switching, which need to be carefully considered in the search for effective policy...

  14. Neurotransmitter Switching? No Surprise.

    Science.gov (United States)

    Spitzer, Nicholas C

    2015-06-03

    Among the many forms of brain plasticity, changes in synaptic strength and changes in synapse number are particularly prominent. However, evidence for neurotransmitter respecification or switching has been accumulating steadily, both in the developing nervous system and in the adult brain, with observations of transmitter addition, loss, or replacement of one transmitter with another. Natural stimuli can drive these changes in transmitter identity, with matching changes in postsynaptic transmitter receptors. Strikingly, they often convert the synapse from excitatory to inhibitory or vice versa, providing a basis for changes in behavior in those cases in which it has been examined. Progress has been made in identifying the factors that induce transmitter switching and in understanding the molecular mechanisms by which it is achieved. There are many intriguing questions to be addressed.

  15. Conservation genetics in transition to conservation genomics

    NARCIS (Netherlands)

    Ouborg, N. Joop; Pertoldi, Cino; Loeschcke, Volker; Bijlsma, R. (Kuke); Hedrick, Phil W.

    2010-01-01

    Over the past twenty years conservation genetics has progressed from being mainly a theory-based field of population biology to a full-grown empirical discipline. Technological developments in molecular genetics have led to extensive use of neutral molecular markers such as microsatellites in conser

  16. Airy-like pulses in models of large molecular chains, and conservative numerical methods for quasi-linear Hamiltonian systems

    CERN Document Server

    LeMesurier, Brenton

    2013-01-01

    The phenomenon of coherent energetic pulse propagation in macromolecular chains such as $\\alpha$-helix protein is studied using the Davydov-Scott model, with both numerical studies using a new unconditionally stable fourth order accurate energy-momentum conserving time discretization, and with analysis based on ideas of center manifold theory. It is shown that for physically natural impulsive initial data, the coherent traveling pulses seen have a form related to the Airy function, but with rapid variation of phase along the chain. This can be explained in terms of a new continuum limit approximation by the third derivative nonlinear Schr\\"odinger equation, which differs from the previous continuum limit approximations related to the standard NLS equation. A theorem is given describing the construction of such conservative time discretizations for a large class of Hamiltonian systems.

  17. The optical theorem for the conservation of the electromagnetic helicity: Its significance for molecular transfer and enantiomeric discrimination by dichroism

    CERN Document Server

    Nieto-Vesperinas, Manuel

    2015-01-01

    We put forward the physical meaning of the conservation equation for the helicity on scattering of an electromagnetic field with a generally magnetodielectric bi-isotropic dipolar object. This is the optical theorem for the helicity that, as we find, plays a role for this quantity analogous to that of the optical thorem for energy. We discuss its consequences for helicity transfer between molecules and for new detection procedures of circular dichroism based on ellipsometric measurements.

  18. Diversified Structural Basis of a Conserved Molecular Mechanism for pH-Dependent Dimerization in Spider Silk N-Terminal Domains.

    Science.gov (United States)

    Otikovs, Martins; Chen, Gefei; Nordling, Kerstin; Landreh, Michael; Meng, Qing; Jörnvall, Hans; Kronqvist, Nina; Rising, Anna; Johansson, Jan; Jaudzems, Kristaps

    2015-08-17

    Conversion of spider silk proteins from soluble dope to insoluble fibers involves pH-dependent dimerization of the N-terminal domain (NT). This conversion is tightly regulated to prevent premature precipitation and enable rapid silk formation at the end of the duct. Three glutamic acid residues that mediate this process in the NT from Euprosthenops australis major ampullate spidroin 1 are well conserved among spidroins. However, NTs of minor ampullate spidroins from several species, including Araneus ventricosus ((Av)MiSp NT), lack one of the glutamic acids. Here we investigate the pH-dependent structural changes of (Av)MiSp NT, revealing that it uses the same mechanism but involves a non-conserved glutamic acid residue instead. Homology modeling of the structures of other MiSp NTs suggests that these harbor different compensatory residues. This indicates that, despite sequence variations, the molecular mechanism underlying pH-dependent dimerization of NT is conserved among different silk types. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. All-atom molecular dynamics simulations reveal significant differences in interaction between antimycin and conserved amino acid residues in bovine and bacterial bc1 complexes.

    Science.gov (United States)

    Kokhan, Oleksandr; Shinkarev, Vladimir P

    2011-02-02

    Antimycin A is the most frequently used specific and powerful inhibitor of the mitochondrial respiratory chain. We used all-atom molecular dynamics (MD) simulations to study the dynamic aspects of the interaction of antimycin A with the Q(i) site of the bacterial and bovine bc(1) complexes embedded in a membrane. The MD simulations revealed considerable conformational flexibility of antimycin and significant mobility of antimycin, as a whole, inside the Q(i) pocket. We conclude that many of the differences in antimycin binding observed in high-resolution x-ray structures may have a dynamic origin and result from fluctuations of protein and antimycin between multiple conformational states of similar energy separated by low activation barriers, as well as from the mobility of antimycin within the Q(i) pocket. The MD simulations also revealed a significant difference in interaction between antimycin and conserved amino acid residues in bovine and bacterial bc(1) complexes. The strong hydrogen bond between antimycin and conserved Asp-228 (bovine numeration) was observed to be frequently broken in the bacterial bc(1) complex and only rarely in the bovine bc(1) complex. In addition, the distances between antimycin and conserved His-201 and Lys-227 were consistently larger in the bacterial bc(1) complex. The observed differences could be responsible for a weaker interaction of antimycin with the bacterial bc(1) complex.

  20. Molecular clonality determination of ipsilateral recurrence of invasive breast carcinomas after breast-conserving therapy: comparison with clinical and biologic factors.

    Science.gov (United States)

    Goldstein, Neal S; Vicini, Frank A; Hunter, Susan; Odish, Eva; Forbes, Suzy; Kraus, Daniel; Kestin, Larry L

    2005-05-01

    We established clonality relationships between invasive ipsilateral breast failures (IBFs; local recurrences) and initial invasive carcinomas using a molecular polymerase chain reaction loss of heterozygosity (LOH) assay for 26 patients treated with breast-conserving therapy for invasive carcinoma with no distant metastases (DMs) before the IBE LOH was +/- 50% allelic loss. Eighteen IBFs (69%) were related clonally to initial carcinomas; 8 (31%) were clonally distinct, second primary carcinomas. IBFs and initial invasive carcinomas were morphologically similar in 6 (75%) of 8 clonally different cases. Clinical IBF classification and molecular assay results differed in 11 cases (42%). The mean intervals to IBF were 4.7 years in related and 8.7 years in different cases (P = .013). In 6 patients, DMs developed; 5 had related IBFs. In related IBF cases, the mean increase in fractional allelic loss (FAL) of IBFs associated with DMs was 18.9% compared with 7.6% in cases unassociated with DMs (P = .004). Molecular assays can accurately establish the clonality of most IBFs. Morphologic comparison and clinical IBF classification are unreliable methods of determining clonality. Clonally related IBFs occurred sooner than clonally different IBFs. Patients with clonally related IBFs are the main pool in which DMs occur Not all clonally related IBFs have the same DM association; those with large FAL gains were associated with DMs. Molecular clonality assays may provide a reliable means of identifying patients who might benefit from systemic chemotherapy at the time of IBF.

  1. Molecular conservation of estrogen-response associated with cell cycle regulation, hormonal carcinogenesis and cancer in zebrafish and human cancer cell lines

    Directory of Open Access Journals (Sweden)

    Govindarajan Kunde R

    2011-05-01

    Full Text Available Abstract Background The zebrafish is recognized as a versatile cancer and drug screening model. However, it is not known whether the estrogen-responsive genes and signaling pathways that are involved in estrogen-dependent carcinogenesis and human cancer are operating in zebrafish. In order to determine the potential of zebrafish model for estrogen-related cancer research, we investigated the molecular conservation of estrogen responses operating in both zebrafish and human cancer cell lines. Methods Microarray experiment was performed on zebrafish exposed to estrogen (17β-estradiol; a classified carcinogen and an anti-estrogen (ICI 182,780. Zebrafish estrogen-responsive genes sensitive to both estrogen and anti-estrogen were identified and validated using real-time PCR. Human homolog mapping and knowledge-based data mining were performed on zebrafish estrogen responsive genes followed by estrogen receptor binding site analysis and comparative transcriptome analysis with estrogen-responsive human cancer cell lines (MCF7, T47D and Ishikawa. Results Our transcriptome analysis captured multiple estrogen-responsive genes and signaling pathways that increased cell proliferation, promoted DNA damage and genome instability, and decreased tumor suppressing effects, suggesting a common mechanism for estrogen-induced carcinogenesis. Comparative analysis revealed a core set of conserved estrogen-responsive genes that demonstrate enrichment of estrogen receptor binding sites and cell cycle signaling pathways. Knowledge-based and network analysis led us to propose that the mechanism involving estrogen-activated estrogen receptor mediated down-regulation of human homolog HES1 followed by up-regulation cell cycle-related genes (human homologs E2F4, CDK2, CCNA, CCNB, CCNE, is highly conserved, and this mechanism may involve novel crosstalk with basal AHR. We also identified mitotic roles of polo-like kinase as a conserved signaling pathway with multiple entry

  2. Large-scale analysis of conserved rare codon clusters suggests an involvement in co-translational molecular recognition events.

    Science.gov (United States)

    Chartier, Matthieu; Gaudreault, Francis; Najmanovich, Rafael

    2012-06-01

    An increasing amount of evidence from experimental and computational analysis suggests that rare codon clusters are functionally important for protein activity. Most of the studies on rare codon clusters were performed on a limited number of proteins or protein families. In the present study, we present the Sherlocc program and how it can be used for large scale protein family analysis of evolutionarily conserved rare codon clusters and their relation to protein function and structure. This large-scale analysis was performed using the whole Pfam database covering over 70% of the known protein sequence universe. Our program Sherlocc, detects statistically relevant conserved rare codon clusters and produces a user-friendly HTML output. Statistically significant rare codon clusters were detected in a multitude of Pfam protein families. The most statistically significant rare codon clusters were predominantly identified in N-terminal Pfam families. Many of the longest rare codon clusters are found in membrane-related proteins which are required to interact with other proteins as part of their function, for example in targeting or insertion. We identified some cases where rare codon clusters can play a regulating role in the folding of catalytically important domains. Our results support the existence of a widespread functional role for rare codon clusters across species. Finally, we developed an online filter-based search interface that provides access to Sherlocc results for all Pfam families. The Sherlocc program and search interface are open access and are available at http://bcb.med.usherbrooke.ca

  3. Superconducting switch pack

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, V.C.; Wollan, J.J.

    1990-07-24

    This patent describes a superconducting switch pack at least one switch element. The switch element including a length of superconductive wire having a switching portion and two lead portions, the switching portion being between the lead portions; means for supporting the switching portion in a plane in a common mold; hardened resin means encapsulating the switching portion in the plane in a solid body; wherein the solid body has an exterior surface which is planar and substantially parallel with and spaced apart from the plane in which the switching portion is positioned. The exterior surface being exposed to the exterior of the switch pack and the resin means filling the space between the exterior surface and the plane of the switching portion so as to provide uninterrupted thermal communication between the plane of the switching portion and the exterior of the switch pack; and a heater element in thermal contact with the switching portion.

  4. Molecular and biochemical analysis of rainbow trout LCK suggests a conserved mechanism for T-cell signaling in gnathostomes

    Science.gov (United States)

    Laing, K.J.; Dutton, S.; Hansen, J.D.

    2007-01-01

    Two genes were identified in rainbow trout that display high sequence identity to vertebrate Lck. Both of the trout Lck transcripts are associated with lymphoid tissues and were found to be highly expressed in IgM-negative lymphocytes. In vitro analysis of trout lymphocytes indicates that trout Lck mRNA is up-regulated by T-cell mitogens, supporting an evolutionarily conserved function for Lck in the signaling pathways of T-lymphocytes. Here, we describe the generation and characterization of a specific monoclonal antibody raised against the N-terminal domains of recombinant trout Lck that can recognize Lck protein(s) from trout thymocyte lysates that are similar in size (???57 kDa) to mammalian Lck. This antibody also reacted with permeabilized lymphocytes during FACS analysis, indicating its potential usage for cellular analyses of trout lymphocytes, thus representing an important tool for investigations of salmonid T-cell function.

  5. Large-scale analysis of conserved rare codon clusters suggests an involvement in co-translational molecular recognition events

    Science.gov (United States)

    Chartier, Matthieu; Gaudreault, Francis; Najmanovich, Rafael

    2012-01-01

    Motivation: An increasing amount of evidence from experimental and computational analysis suggests that rare codon clusters are functionally important for protein activity. Most of the studies on rare codon clusters were performed on a limited number of proteins or protein families. In the present study, we present the Sherlocc program and how it can be used for large scale protein family analysis of evolutionarily conserved rare codon clusters and their relation to protein function and structure. This large-scale analysis was performed using the whole Pfam database covering over 70% of the known protein sequence universe. Our program Sherlocc, detects statistically relevant conserved rare codon clusters and produces a user-friendly HTML output. Results: Statistically significant rare codon clusters were detected in a multitude of Pfam protein families. The most statistically significant rare codon clusters were predominantly identified in N-terminal Pfam families. Many of the longest rare codon clusters are found in membrane-related proteins which are required to interact with other proteins as part of their function, for example in targeting or insertion. We identified some cases where rare codon clusters can play a regulating role in the folding of catalytically important domains. Our results support the existence of a widespread functional role for rare codon clusters across species. Finally, we developed an online filter-based search interface that provides access to Sherlocc results for all Pfam families. Availability: The Sherlocc program and search interface are open access and are available at http://bcb.med.usherbrooke.ca Contact: rafael.najmanovich@usherbrooke.ca Supplementary information: Supplementary data are available at Bioinformatics online. PMID:22467916

  6. Magnetic switching

    Energy Technology Data Exchange (ETDEWEB)

    Birx, D.; Cook, E.; Hawkins, S.; Poor, S.; Reginato, L.; Schmidt, J.; Smith, M.

    1983-06-01

    The paper discusses the development program in magnetic switching which was aimed at solving the rep-rate and reliability limitations of the ATA spark gaps. The end result has been a prototype physically very similar to the present Advanced Test Accelerator (ATA) pulse power unit but vastly superior in performance. This prototype, which is easily adaptable to the existing systems, has achieved a burst rep-rate of 20 kHz and an output voltage of 500 kV. A one-on-one substitution of the existing pulse power module would result in a 100 MeV accelerator. Furthermore, the high efficiency of the magnetic pulse compression stages has allowed CW operation of the prototype at one kilohertz opening up other applications for the pulse power. Performance and design details will be described.

  7. Protocols for In Vitro Propagation, Conservation, Synthetic Seed Production, Embryo Rescue, Microrhizome Production, Molecular Profiling, and Genetic Transformation in Ginger (Zingiber officinale Roscoe.).

    Science.gov (United States)

    Nirmal Babu, K; Samsudeen, K; Divakaran, Minoo; Pillai, Geetha S; Sumathi, V; Praveen, K; Ravindran, P N; Peter, K V

    2016-01-01

    Ginger is a rhizomatous plant that belongs to the family Zingiberaceae. It is a herbaceous perennial but cultivated as annual, with crop duration of 7-10 months. Ginger is native to India and Tropical South Asia. The tuberous rhizomes or underground stems of ginger are used as condiment, an aromatic stimulant, and food preservative as well as in traditional medicine. Ginger is propagated vegetatively with rhizome bits as seed material. Cultivation of ginger is plagued by rhizome rot diseases, most of which are mainly spread through infected seed rhizomes. Micropropagation will help in production of disease-free planting material. Sexual reproduction is absent in ginger, making recombinant breeding very impossible. In vitro technology can thus become the preferred choice as it can be utilized for multiplication, conservation of genetic resources, generating variability, gene transfer, molecular tagging, and their utility in crop improvement of these crops.

  8. A highly conserved N-terminal sequence for teleost vitellogenin with potential value to the biochemistry, molecular biology and pathology of vitellogenesis

    Science.gov (United States)

    Folmar, L.D.; Denslow, N.D.; Wallace, R.A.; LaFleur, G.; Gross, T.S.; Bonomelli, S.; Sullivan, C.V.

    1995-01-01

    N-terminal amino acid sequences for vitellogenin (Vtg) from six species of teleost fish (striped bass, mummichog, pinfish, brown bullhead, medaka, yellow perch and the sturgeon) are compared with published N-terminal Vtg sequences for the lamprey, clawed frog and domestic chicken. Striped bass and mummichog had 100% identical amino acids between positions 7 and 21, while pinfish, brown bullhead, sturgeon, lamprey, Xenopus and chicken had 87%, 93%, 60%, 47%, 47-60%) for four transcripts and had 40% identical, respectively, with striped bass for the same positions. Partial sequences obtained for medaka and yellow perch were 100% identical between positions 5 to 10. The potential utility of this conserved sequence for studies on the biochemistry, molecular biology and pathology of vitellogenesis is discussed.

  9. Molecular evolution of vertebrate neurotrophins: co-option of the highly conserved nerve growth factor gene into the advanced snake venom arsenalf.

    Directory of Open Access Journals (Sweden)

    Kartik Sunagar

    Full Text Available Neurotrophins are a diverse class of structurally related proteins, essential for neuronal development, survival, plasticity and regeneration. They are characterized by major family members, such as the nerve growth factors (NGF, brain-derived neurotrophic factors (BDNF and neurotrophin-3 (NT-3, which have been demonstrated here to lack coding sequence variations and follow the regime of negative selection, highlighting their extremely important conserved role in vertebrate homeostasis. However, in stark contrast, venom NGF secreted as part of the chemical arsenal of the venomous advanced snake family Elapidae (and to a lesser extent Viperidae have characteristics consistent with the typical accelerated molecular evolution of venom components. This includes a rapid rate of diversification under the significant influence of positive-selection, with the majority of positively-selected sites found in the secreted β-polypeptide chain (74% and on the molecular surface of the protein (92%, while the core structural and functional residues remain highly constrained. Such focal mutagenesis generates active residues on the toxin molecular surface, which are capable of interacting with novel biological targets in prey to induce a myriad of pharmacological effects. We propose that caenophidian NGFs could participate in prey-envenoming by causing a massive release of chemical mediators from mast cells to mount inflammatory reactions and increase vascular permeability, thereby aiding the spread of other toxins and/or by acting as proapoptotic factors. Despite their presence in reptilian venom having been known for over 60 years, this is the first evidence that venom-secreted NGF follows the molecular evolutionary pattern of other venom components, and thus likely participates in prey-envenomation.

  10. Conserving the linear momentum in stochastic dynamics: Dissipative particle dynamics as a general strategy to achieve local thermostatization in molecular dynamics simulations.

    Science.gov (United States)

    Passler, Peter P; Hofer, Thomas S

    2017-02-15

    Stochastic dynamics is a widely employed strategy to achieve local thermostatization in molecular dynamics simulation studies; however, it suffers from an inherent violation of momentum conservation. Although this short-coming has little impact on structural and short-time dynamic properties, it can be shown that dynamics in the long-time limit such as diffusion is strongly dependent on the respective thermostat setting. Application of the methodically similar dissipative particle dynamics (DPD) provides a simple, effective strategy to ensure the advantages of local, stochastic thermostatization while at the same time the linear momentum of the system remains conserved. In this work, the key parameters to employ the DPD thermostats in the framework of periodic boundary conditions are investigated, in particular the dependence of the system properties on the size of the DPD-region as well as the treatment of forces near the cutoff. Structural and dynamical data for light and heavy water as well as a Lennard-Jones fluid have been compared to simulations executed via stochastic dynamics as well as via use of the widely employed Nose-Hoover chain and Berendsen thermostats. It is demonstrated that a small size of the DPD region is sufficient to achieve local thermalization, while at the same time artifacts in the self-diffusion characteristic for stochastic dynamics are eliminated. © 2016 Wiley Periodicals, Inc.

  11. Analysis and validation of genome-specific DNA variations in 5' flanking conserved sequences of wheat low-molecular-weight glutenin subunit genes

    Institute of Scientific and Technical Information of China (English)

    LONG; Hai; WEI; Yuming

    2006-01-01

    The thirty-three 5' flanking conserved sequences of the known low-molecular-weight subunit (LMW-GS) genes have been divided into eight clusters, which was in agreement with the classification based on the deduced N-terminal protein sequences. The DNA polymorphism between the eight clusters was obtained by sequence alignment, and a total of 34 polymorphic positions were observed in the approximately 200 bp regions, among which 18 polymorphic positions were candidate SNPs. Seven cluster-specific primer sets were designed for seven out of eight clusters containing cluster-specific bases, with which the genomic DNA of the ditelosomic lines of group 1 chromosomes of a wheat variety 'Chinese Spring' was employed to carry out chromosome assignment. The subsequent cloning and DNA sequencing of PCR fragments validated the sequences specificity of the 5' flanking conserved sequences between LMW-GS gene groups in different genomes. These results suggested that the coding and 5' flanking regions of LMW-GS genes are likely to have evolved in a concerted fashion. The seven primer sets developed in this study could be used to isolate the complete ORFs of seven groups of LMW-GS genes, respectively, and therefore possess great value for further research in the contributions of a single LMW-GS gene to wheat quality in the complex genetic background and the efficient selections of quality-related components in breeding programs.

  12. Molecular dissection of a contiguous gene syndrome: Frequent submicroscopic deletions, evolutionarily conserved sequences, and a hypomethylated island in the Miller-Dieker chromosome region

    Energy Technology Data Exchange (ETDEWEB)

    Ledbetter, D.H.; Ledbetter, S.A.; vanTuinen, P.; Summers, K.M.; Robinson, T.J.; Nakamura, Yusuke; Wolff, R.; White, R.; Barker, D.F.; Wallace, M.R.; Collins, F.S.; Dobyns, W.B. (Baylor College of Medicine, Houston, TX (USA))

    1989-07-01

    The Miller-Dieker syndrome (MDS), composed of characteristic facial abnormalities and a severe neuronal migration disorder affecting the cerebral cortex, is caused by visible or submicroscopic deletions of chromosome band 17p13. Twelve anonymous DNA markers were tested against a panel of somatic cell hybrids containing 17p deletions from seven MDS patients. All patients, including three with normal karyotypes, are deleted for a variable set of 5-12 markers. Two highly polymorphic VNTR (variable number of tandem repeats) probes, YNZ22 and YNH37, are codeleted in all patients tested and make molecular diagnosis for this disorder feasible. By pulsed-field gel electrophoresis, YNZ22 and YNH37 were shown to be within 30 kilobases (kb) of each other. Cosmid clones containing both VNTR sequences were identified, and restriction mapping showed them to be <15 kb apart. Three overlapping cosmids spanning >100 kb were completely deleted in all patients, providing a minimum estimate of the size of the MDS critical region. A hypomethylated island and evolutionarily conserved sequences were identified within this 100-kb region, indications of the presence of one or more expressed sequences potentially involved in the pathophysiology of this disorder. The conserved sequences were mapped to mouse chromosome 11 by using mouse-rat somatic cell hybrids, extending the remarkable homology between human chromosome 17 and mouse chromosome 11 by 30 centimorgans, into the 17p telomere region.

  13. Decision maker based on atomic switches

    OpenAIRE

    Song-Ju Kim; Tohru Tsuruoka; Tsuyoshi Hasegawa; Masashi Aono; Kazuya Terabe; Masakazu Aono

    2016-01-01

    We propose a simple model for an atomic switch-based decision maker (ASDM), and show that, as long as its total number of metal atoms is conserved when coupled with suitable operations, an atomic switch system provides a sophisticated ``decision-making'' capability that is known to be one of the most important intellectual abilities in human beings. We considered a popular decision-making problem studied in the context of reinforcement learning, the multi-armed bandit problem (MAB); the probl...

  14. An insight to conserved water molecular dynamics of catalytic and structural Zn(+2) ions in matrix metalloproteinase 13 of human.

    Science.gov (United States)

    Chakrabarti, Bornali; Bairagya, Hridoy R; Mallik, Payel; Mukhopadhyay, Bishnu P; Bera, Asim K

    2011-02-01

    Matrix Metalloproteinase (MMP)--13 or Collagenase--3 plays a significant role in the formation and remodeling of bone, tumor invasion and causes osteoarthritis. Water molecular dynamic studies of the five (1XUC, 1XUD, 1XUR, 456C, 830C) PDB and solvated structures of MMP-13 in human have been carried out upto 5 ns on assigning the differential charges (+2, +1, +0.5 e) to both the Zinc ions. The MM and MD-studies have revealed the coordination of three water molecules (W(H), W(I) and W(S)) to Zn(c) and one water to Zn(s). The transition of geometry around the Znc from tetrahedral to octahedral via trigonal bipyramidal, and for Zn(s) from tetrahedral to trigonal bipyramidal are seem interesting. Recognition of two zinc ions through water molecular bridging (Zn(c) - W(H) (W(1))...W(2)....W(3)....H(187) Zn(s)) and the stabilization of variable coordination geometries around metal ions may indicate the possible involvement of Zn(c) ...Zn(s) coupled mechanism in the catalytic process. So the hydrophilic topology and stereochemistry of water mediated coupling between Zn-ions may provide some plausible hope towards the design of some bidentate/polydentate bridging ligands or inhibitors for MMP-13.

  15. Gate-controlled conductance switching in DNA

    Science.gov (United States)

    Xiang, Limin; Palma, Julio L.; Li, Yueqi; Mujica, Vladimiro; Ratner, Mark A.; Tao, Nongjian

    2017-02-01

    Extensive evidence has shown that long-range charge transport can occur along double helical DNA, but active control (switching) of single-DNA conductance with an external field has not yet been demonstrated. Here we demonstrate conductance switching in DNA by replacing a DNA base with a redox group. By applying an electrochemical (EC) gate voltage to the molecule, we switch the redox group between the oxidized and reduced states, leading to reversible switching of the DNA conductance between two discrete levels. We further show that monitoring the individual conductance switching allows the study of redox reaction kinetics and thermodynamics at single molecular level using DNA as a probe. Our theoretical calculations suggest that the switch is due to the change in the energy level alignment of the redox states relative to the Fermi level of the electrodes.

  16. Generation and molecular characterization of a monoclonal antibody reactive with conserved epitope in sphingomyelinases D from Loxosceles spider venoms.

    Science.gov (United States)

    Dias-Lopes, C; Felicori, L; Rubrecht, L; Cobo, S; Molina, L; Nguyen, C; Galéa, P; Granier, C; Molina, F; Chávez-Olortegui, C

    2014-04-11

    We report the production of a neutralizing monoclonal antibody able to recognize the venoms of three major medically important species of Loxosceles spiders in Brazil. The mAb was produced by immunization of mice with a toxic recombinant L. intermedia sphingomyelinase D {SMases D isoform (rLiD1)} [1] and screened by enzyme-linked immunosorbent assay (ELISA) using L. intermedia, L. laeta and L. gaucho venoms as antigens. One clone (LiD1mAb16) out of seventeen anti-rLiD1 hybridomas was cross-reactive with the three whole Loxosceles venoms. 2D Western blot analysis indicated that LiD1mAb16 was capable of interacting with 34 proteins of 29-36kDa in L. intermedia, 33 in L. gaucho and 27 in L. laeta venoms. The results of immunoassays with cellulose-bound peptides revealed that the LiD1mAb16 recognizes a highly conserved linear epitope localized in the catalytic region of SMases D toxins. The selected mAb displayed in vivo protective activity in rabbits after challenge with rLiD1. These results show the potential usefulness of monoclonal antibodies for future therapeutic approaches and also opens up the perspective of utilization of these antibodies for immunodiagnostic assays in loxoscelism.

  17. The Prognostic Impact of Molecular Subtypes and Very Young Age on Breast Conserving Surgery in Early Stage Breast Cancer

    Science.gov (United States)

    McGuire, Kandace; Alco, Gul; Nur Pilanci, Kezban; Koksal, Ulkuhan I; Elbüken, Filiz; Erdogan, Zeynep; Agacayak, Filiz; Ilgun, Serkan; Sarsenov, Dauren; Öztürk, Alper; İğdem, Şefik; Okkan, Sait; Eralp, Yeşim; Dincer, Maktav; Ozmen, Vahit

    2016-01-01

    Background Premenopausal breast cancer with a triple-negative phenotype (TNBC) has been associated with inferior locoregional recurrence free survival (LRFS) and overall survival (OS) after breast conserving surgery (BCS). The aim of this study is to analyze the association between age, subtype, and surgical treatment on survival in young women (≤40 years) with early breast cancer in a population with a high rate of breast cancer in young women. Methods Three hundred thirty-two patients ≤40 years old with stage I-II invasive breast cancer who underwent surgery at a single institution between 1998 and 2012 were identified retrospectively. Uni- and multivariate analysis evaluated predictors of LRFS, OS, and disease free survival (DFS). Results Most patients (64.2%) underwent BCS. Mean age and follow-up time were 35 (25 ± 3.61) years, and 72 months (range, 24–252), respectively. In multivariate analysis, multicentricity/multifocality and young age (<35 years) independently predicted for poorer DFS and OS. Those aged 35–40 years had higher LRFS and DFS than those <35 in the mastectomy group (p=0.007 and p=0.039, respectively). Patients with TNBC had lower OS compared with patients with luminal A subtype (p=0.042), and those who underwent BCS had higher OS than patients after mastectomy (p=0.015). Conclusion Young age (< 35 years) is an independent predictor of poorer OS and DFS as compared with ages 35–40, even in countries with a lower average age of breast cancer presentation. In addition, TNBC in the young predicts for poorer OS. BCS can be performed in young patients with TNBC, despite their poorer overall survival. PMID:27433412

  18. Crystal structure of the WOPR-DNA complex and implications for Wor1 function in white-opaque switching of Candida albicans.

    Science.gov (United States)

    Zhang, Shicheng; Zhang, Tianlong; Yan, Minghui; Ding, Jianping; Chen, Jiangye

    2014-09-01

    Wor1 (white-opaque switching regulator 1) is a master regulator of the white-opaque switching in Candida albicans, an opportunistic human fungal pathogen, and is associated with its pathogenicity and commensality. Wor1 contains a conserved DNA-binding region at the N-terminus, consisting of two conserved segments (WOPRa and WOPRb) connected by a non-conserved linker that can bind to specific DNA sequences of the promoter regions and then regulates the transcription. Here, we report the crystal structure of the C. albicans Wor1 WOPR segments in complex with a double-stranded DNA corresponding to one promoter region of WOR1. The sequentially separated WOPRa and WOPRb are structurally interwound together to form a compact globular domain that we term the WOPR domain. The WOPR domain represents a new conserved fungal-specific DNA-binding domain which uses primarily a conserved loop to recognize and interact specifically with a conserved 6-bp motif of the DNA in both minor and major grooves. The protein-DNA interactions are essential for WOR1 transcriptional regulation and white-to-opaque switching. The structural and biological data together reveal the molecular basis for the recognition and binding specificity of the WOPR domain with its specific DNA sequences and the function of Wor1 in the activation of transcription.

  19. Stability conditions of complex switched systems with unstable subsystems

    Institute of Scientific and Technical Information of China (English)

    肖扬

    2004-01-01

    New stability conditions for complex switched systems are presented. We propose the concepts of attractive region and semi-attractive region, which are used as a tool for analyzing the stability of switched systems with unstable subsystems. Based on attractive region the sufficient conditions with less conservative for stability of switched systems have been established, there is no limitation for all members of the system set to be stable. Since our results have considered and utilized the decreasing span of oscillating solutions of the switched systems, they are more practical than the other presented ones of stability of switched systems, and need not resort to multiple Lyapunov functions.

  20. Switched on!

    CERN Multimedia

    2008-01-01

    Like a star arriving on stage, impatiently followed by each member of CERN personnel and by millions of eyes around the world, the first beam of protons has circulated in the LHC. After years in the making and months of increasing anticipation, today the work of hundreds of people has borne fruit. WELL DONE to all! Successfully steered around the 27 kilometres of the world’s most powerful particle accelerator at 10:28 this morning, this first beam of protons circulating in the ring marks a key moment in the transition from over two decades of preparation to a new era of scientific discovery. "It’s a fantastic moment," said the LHC project leader Lyn Evans, "we can now look forward to a new era of understanding about the origins and evolution of the universe". Starting up a major new particle accelerator takes much more than flipping a switch. Thousands of individual elements have to work in harmony, timings have to be synchronize...

  1. Valley blockade quantum switching in Silicon nanostructures.

    Science.gov (United States)

    Prati, Enrico

    2011-10-01

    In analogy to the Coulomb and the Pauli spin blockade, based on the electrostatic repulsion and the Pauli exclusion principle respectively, the concept of valley blockade in Silicon nanostructures is explored. The valley parity operator is defined. Valley blockade is determined by the parity conservation of valley composition eigenvectors in quantum transport. A Silicon quantum changeover switch based on a triple of donor quantum dots capable to separate electrons having opposite valley parity by virtue of the valley parity conservation is proposed. The quantum changeover switch represents a novel kind of hybrid quantum based classical logic device.

  2. Speed switching of gonococcal surface motility correlates with proton motive force.

    Directory of Open Access Journals (Sweden)

    Rainer Kurre

    Full Text Available Bacterial type IV pili are essential for adhesion to surfaces, motility, microcolony formation, and horizontal gene transfer in many bacterial species. These polymers are strong molecular motors that can retract at two different speeds. In the human pathogen Neisseria gonorrhoeae speed switching of single pili from 2 µm/s to 1 µm/s can be triggered by oxygen depletion. Here, we address the question how proton motive force (PMF influences motor speed. Using pHluorin expression in combination with dyes that are sensitive to transmembrane ΔpH gradient or transmembrane potential ΔΨ, we measured both components of the PMF at varying external pH. Depletion of PMF using uncouplers reversibly triggered switching into the low speed mode. Reduction of the PMF by ≈ 35 mV was enough to trigger speed switching. Reducing ATP levels by inhibition of the ATP synthase did not induce speed switching. Furthermore, we showed that the strictly aerobic Myxococcus xanthus failed to move upon depletion of PMF or oxygen, indicating that although the mechanical properties of the motor are conserved, its regulatory inputs have evolved differently. We conclude that depletion of PMF triggers speed switching of gonococcal pili. Although ATP is required for gonococcal pilus retraction, our data indicate that PMF is an independent additional energy source driving the high speed mode.

  3. Efficient somatic embryogenesis and molecular marker based analysis as effective tools for conservation of red-listed plant Commiphora wightii

    Directory of Open Access Journals (Sweden)

    ASHOK KUMAR PARMAR

    2014-08-01

    Full Text Available A refined and high efficiency protocol for in vitro regeneration of Commiphora wightii, a red-listed medicinal plant of medicinal importance, has been developed through optimized somatic embryogenesis pathway. Cultures from immature fruits were induced and proliferated on B5 medium supplemented with 2.26 µM 2,4-D. Embryogenic calli were obtained and then maintained for extended periods by alternately subculturing on modified MS medium supplemented with 1.11 µM BAP, 0.57 µM IBA and with 0.5% activated charcoal or without PGR every 3-4 weeks. Cyclic embryogenesis was obtained. Late torpedo and early cotyledonary stages somatic embryos were regularly harvested from PGR-free modified MS medium. It was found that percent moisture available in culture containers play a critical role in maturation and subsequent germination of somatic embryos of C. wighti. Maximum germination of more than 80% was achieved through media recycling. Somatic embryo derived plants (emblings were acclimatized. After 5 months, acclimatized plants were out-planted in experimental field. These morphologically normal plants have been surviving for over 3 years. Molecular polymorphism was clearly evident when these plants were tested using RAPD primers, making the plants suitable for use in its species restoration program.

  4. Recurrent disruption of the Imu splice donor site in t(14;18) positive lymphomas: a potential molecular basis for aberrant downstream class switch recombination.

    Science.gov (United States)

    Ruminy, Philippe; Jardin, Fabrice; Penther, Dominique; Picquenot, Jean-Michel; Parmentier, Françoise; Buchonnet, Gérard; Bertrand, Philippe; Tilly, Hervé; Bastard, Christian

    2007-08-01

    t(14;18) positive lymphomas are mature germinal center B-cell neoplasms. In agreement with this cellular origin, most have somatically mutated immunoglobulin variable genes and the IGH@ locus has almost always been reorganized by class switch recombination (CSR). However, contrasting with normal B-cells, a majority of cases still express an IgM while the constant genes are normally rearranged only on the non-productive allele. Concurrently, aberrant intra-allelic junctions involving downstream switch regions, with a lack of engagement of the switch mu (Smu), often accumulate on the functional alleles, suggesting some recurrent CSR perturbation during the onset of the disease. To clarify these surprising observations, we addressed the accessibility of the Smu to the CSR machinery in a large series of patients by characterizing the mutations that are expected to accumulate at this place upon CSR activation. Our data indicate that the Smu is mutated in a large majority of cases, often on both alleles, indicating that these cells usually reach a differentiation stage where CSR is activated and where this region remains accessible. Interestingly, we also identified a significant cluster of mutations at the splicing donor site of the first exon of the Smu germline transcripts, on the functional allele. This location suggests a possible relation with CSR perturbations in lymphoma and the clustering points to a probable mechanism of selection. In conclusion, our data suggest that an acquired mutation at the splicing donor site of the Smu transcripts may participate in the selection of lymphoma cells and play a significant role during the onset of the disease.

  5. Molecular and Genetic Characterization of HIV-1 Tat Exon-1 Gene from Cameroon Shows Conserved Tat HLA-Binding Epitopes: Functional Implications

    Science.gov (United States)

    Teto, Georges; Fonsah, Julius Y.; Tagny, Claude T.; Mbanya, Dora; Nchindap, Emilienne; Kenmogne, Leopoldine; Fokam, Joseph; Njamnshi, Dora M.; Kouanfack, Charles; Njamnshi, Alfred K.; Kanmogne, Georgette D.

    2016-01-01

    HIV-1 Tat plays a critical role in viral transactivation. Subtype-B Tat has potential use as a therapeutic vaccine. However, viral genetic diversity and population genetics would significantly impact the efficacy of such a vaccine. Over 70% of the 37-million HIV-infected individuals are in sub-Saharan Africa (SSA) and harbor non-subtype-B HIV-1. Using specimens from 100 HIV-infected Cameroonians, we analyzed the sequences of HIV-1 Tat exon-1, its functional domains, post-translational modifications (PTMs), and human leukocyte antigens (HLA)-binding epitopes. Molecular phylogeny revealed a high genetic diversity with nine subtypes, CRF22_01A1/CRF01_AE, and negative selection in all subtypes. Amino acid mutations in Tat functional domains included N24K (44%), N29K (58%), and N40K (30%) in CRF02_AG, and N24K in all G subtypes. Motifs and phosphorylation analyses showed conserved amidation, N-myristoylation, casein kinase-2 (CK2), serine and threonine phosphorylation sites. Analysis of HLA allelic frequencies showed that epitopes for HLAs A*0205, B*5301, Cw*0401, Cw*0602, and Cw*0702 were conserved in 58%–100% of samples, with B*5301 epitopes having binding affinity scores > 100 in all subtypes. This is the first report of N-myristoylation, amidation, and CK2 sites in Tat; these PTMs and mutations could affect Tat function. HLA epitopes identified could be useful for designing Tat-based vaccines for highly diverse HIV-1 populations, as in SSA. PMID:27438849

  6. Molecular sensing of bacteria in plants. The highly conserved RNA-binding motif RNP-1 of bacterial cold shock proteins is recognized as an elicitor signal in tobacco.

    Science.gov (United States)

    Felix, Georg; Boller, Thomas

    2003-02-21

    To detect microbial infection multicellular organisms have evolved sensing systems for pathogen-associated molecular patterns (PAMPs). Here, we identify bacterial cold shock protein (CSP) as a new such PAMP that acts as a highly active elicitor of defense responses in tobacco. Tobacco cells perceive a conserved domain of CSP and synthetic peptides representing 15 amino acids of this domain-induced responses at subnanomolar concentrations. Central to the elicitor-active domain is the RNP-1 motif KGFGFITP, a motif conserved also in many RNA- and DNA-binding proteins of eukaryotes. Csp15-Nsyl, a peptide representing the domain with highest homology to csp15 in a protein of Nicotiana sylvestris exhibited only weak activity in tobacco cells. Crystallographic and genetic data from the literature show that the RNP-1 domain of bacterial CSPs resides on a protruding loop and exposes a series of aromatic and basic side chains to the surface that are essential for the nucleotide-binding activity of CSPs. Similarly, these side chains were also essential for elicitor activity and replacement of single residues in csp15 with Ala strongly reduced or abolished activity. Most strikingly, csp15-Ala10, a peptide with the RNP-1 motif modified to KGAGFITP, lacked elicitor activity but acted as a competitive antagonist for CSP-related elicitors. Bacteria commonly have a small family of CSP-like proteins including both cold-inducible and noninducible members, and Csp-related elicitor activity was detected in extracts from all bacteria tested. Thus, the CSP domain containing the RNP-1 motif provides a structure characteristic for bacteria in general, and tobacco plants have evolved a highly sensitive chemoperception system to detect this bacterial PAMP.

  7. Novel colorimetric molecular switch based on copper(I)-catalyzed azide-alkyne cycloaddition reaction and its application for flumioxazin detection.

    Science.gov (United States)

    Xie, Lidan; Zheng, Hanye; Ye, Wenmei; Qiu, Suyan; Lin, Zhenyu; Guo, Longhua; Qiu, Bin; Chen, Guonan

    2013-01-21

    A novel colorimetric switch based on the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction has been developed. G-quadruplex-hemin DNAzyme catalyzes the oxidation of 2,2'-azinobis(3-ethylbenzothiozoline)-6-sulfonic acid (ABTS) to form ABTS˙(+), the UV absorbance of the solution increased greatly and the color of the solution changed to dark green. However, in the presence of an azide complex, the absorbance signal decreased and the solution became light green since the catalytic ability of the hemin was inhibited by the azide groups. However, once propargylamine has been added into the above reaction system, which would react with azide groups through the CuAAC reaction, the solution becomes dark green again and the absorption intensity of the system is also increased. The proposed switch allows a good reversibility and can be identified clearly by the naked eye. In addition, the method has been applied to detect some pesticides, which have alkynyl groups (flumioxazin), with high sensitivity and selectivity, where the UV absorbance has a direct linear relationship with the logarithm of flumioxazin concentrations in the range of 0.14-14 nM, and the limit of detection was 0.056 nM (S/N = 3), which can meet the requirement of the maximum residue limits (MRLs) of United States of America (56 nM).

  8. Molecular Transducers from Roots Are Triggered in Arabidopsis Leaves by Root-Knot Nematodes for Successful Feeding Site Formation: A Conserved Post-Embryogenic De novo Organogenesis Program?

    Directory of Open Access Journals (Sweden)

    Rocío Olmo

    2017-05-01

    Full Text Available Root-knot nematodes (RKNs; Meloidogyne spp. induce feeding cells (giant cells; GCs inside a pseudo-organ (gall from still unknown root cells. Understanding GCs ontogeny is essential to the basic knowledge of RKN–plant interaction and to discover novel and effective control strategies. Hence, we report for the first time in a model plant, Arabidopsis, molecular, and cellular features concerning ectopic de novo organogenesis of RKNs GCs in leaves. RKNs induce GCs in leaves with irregular shape, a reticulated cytosol, and fragmented vacuoles as GCs from roots. Leaf cells around the nematode enter G2-M shown by ProCycB1;1:CycB1;1(NT-GUS expression, consistent to multinucleated GCs. In addition, GCs nuclei present irregular and varied sizes. All these characteristics mentioned, being equivalent to GCs in root-galls. RKNs complete their life cycle forming a gall/callus-like structure in the leaf vascular tissues resembling auxin-induced callus with an auxin-response maxima, indicated by high expression of DR5::GUS that is dependent on leaf auxin-transport. Notably, induction of leaves calli/GCs requires molecular components from roots crucial for lateral roots (LRs, auxin-induced callus and root-gall formation, i.e., LBD16. Hence, LBD16 is a xylem pole pericycle specific and local marker in LR primordia unexpectedly induced locally in the vascular tissue of leaves after RKN infection. LBD16 is also fundamental for feeding site formation as RKNs could not stablish in 35S::LBD16-SRDX leaves, and likely it is also a conserved molecular hub between biotic and developmental signals in Arabidopsis either in roots or leaves. Moreover, RKNs induce the ectopic development of roots from leaf and root-galls, also formed in mutants compromised in LR formation, arf7/arf19, slr, and alf4. Therefore, nematodes must target molecular signatures to induce post-embryogenic de novo organogenesis through the LBD16 callus formation pathway partially different from those

  9. Targeting N-Glycan Cryptic Sugar Moieties for Broad-Spectrum Virus Neutralization: Progress in Identifying Conserved Molecular Targets in Viruses of Distinct Phylogenetic Origins

    Directory of Open Access Journals (Sweden)

    Denong Wang

    2015-03-01

    Full Text Available Identifying molecular targets for eliciting broadly virus-neutralizing antibodies is one of the key steps toward development of vaccines against emerging viral pathogens. Owing to genomic and somatic diversities among viral species, identifying protein targets for broad-spectrum virus neutralization is highly challenging even for the same virus, such as HIV-1. However, viruses rely on host glycosylation machineries to synthesize and express glycans and, thereby, may display common carbohydrate moieties. Thus, exploring glycan-binding profiles of broad-spectrum virus-neutralizing agents may provide key information to uncover the carbohydrate-based virus-neutralizing epitopes. In this study, we characterized two broadly HIV-neutralizing agents, human monoclonal antibody 2G12 and Galanthus nivalis lectin (GNA, for their viral targeting activities. Although these agents were known to be specific for oligomannosyl antigens, they differ strikingly in virus-binding activities. The former is HIV-1 specific; the latter is broadly reactive and is able to neutralize viruses of distinct phylogenetic origins, such as HIV-1, severe acute respiratory syndrome coronavirus (SARS-CoV, and human cytomegalovirus (HCMV. In carbohydrate microarray analyses, we explored the molecular basis underlying the striking differences in the spectrum of anti-virus activities of the two probes. Unlike 2G12, which is strictly specific for the high-density Man9GlcNAc2Asn (Man9-clusters, GNA recognizes a number of N-glycan cryptic sugar moieties. These include not only the known oligomannosyl antigens but also previously unrecognized tri-antennary or multi-valent GlcNAc-terminating N-glycan epitopes (Tri/m-Gn. These findings highlight the potential of N-glycan cryptic sugar moieties as conserved targets for broad-spectrum virus neutralization and suggest the GNA-model of glycan-binding warrants focused investigation.

  10. Understanding the molecular basis of stability in Kunitz (STI) family of inhibitors in terms of a conserved core tryptophan residue: A theoretical investigation.

    Science.gov (United States)

    Datta Sharma, Ravi; Goswami, Nabajyoti; Ghosh, Debasree; Majumder, Sudip

    2017-08-01

    β-trefoil is one of the superfolds among proteins. Important classes of proteins like Interleukins (ILs), FibroblastGrowth Factors (FGFs), Kunitz (STI) family of inhibitors etc. belong to this fold. Kunitz (STI) family of inhibitors of proteins possess a highly conserved and structurally important Trytophan 91 (W91) residue, which stitches the top layer of the barrel with the lid. In this article we have investigated the molecular insights of the involvement of this W91 residue in the stability and folding pathway of Kunitz (STI) family. Winged bean Chymotrypsin inhibitor (WCI), a member of Kunitz (STI) family was chosen as a model system for carrying out the work. Molecular dynamics (MD) simulations were run with a set of total six proteins, including wild type WCI (WT) & five mutants namely W91F, W91M, W91A, W91H and W91I. Among all of them the coordinates of four proteins were taken from their crystal structures deposited in the Protein Data Bank (PDB), where as the coordinates for the rest two was generated using in-silico modelling. Our results suggest that truly this W91 residue plays a determining role in stability and folding pathway of Kunitz (STI) family. The mutants are less stable and more susceptible to quicker unfolding at higher temperatures compared to the wild type WCI. These effects are most pronounced for the smallest mutants namely W91H and W91A, indicating more is the cavity created by mutation at W91 position more the proteins becomes unstable. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. From Amazonia to the Atlantic forest: molecular phylogeny of Phyzelaphryninae frogs reveals unexpected diversity and a striking biogeographic pattern emphasizing conservation challenges.

    Science.gov (United States)

    Fouquet, Antoine; Loebmann, Daniel; Castroviejo-Fisher, Santiago; Padial, José M; Orrico, Victor G D; Lyra, Mariana L; Roberto, Igor Joventino; Kok, Philippe J R; Haddad, Célio F B; Rodrigues, Miguel T

    2012-11-01

    Documenting the Neotropical amphibian diversity has become a major challenge facing the threat of global climate change and the pace of environmental alteration. Recent molecular phylogenetic studies have revealed that the actual number of species in South American tropical forests is largely underestimated, but also that many lineages are millions of years old. The genera Phyzelaphryne (1 sp.) and Adelophryne (6 spp.), which compose the subfamily Phyzelaphryninae, include poorly documented, secretive, and minute frogs with an unusual distribution pattern that encompasses the biotic disjunction between Amazonia and the Atlantic forest. We generated >5.8 kb sequence data from six markers for all seven nominal species of the subfamily as well as for newly discovered populations in order to (1) test the monophyly of Phyzelaphryninae, Adelophryne and Phyzelaphryne, (2) estimate species diversity within the subfamily, and (3) investigate their historical biogeography and diversification. Phylogenetic reconstruction confirmed the monophyly of each group and revealed deep subdivisions within Adelophryne and Phyzelaphryne, with three major clades in Adelophryne located in northern Amazonia, northern Atlantic forest and southern Atlantic forest. Our results suggest that the actual number of species in Phyzelaphryninae is, at least, twice the currently recognized species diversity, with almost every geographically isolated population representing an anciently divergent candidate species. Such results highlight the challenges for conservation, especially in the northern Atlantic forest where it is still degraded at a fast pace. Molecular dating revealed that Phyzelaphryninae originated in Amazonia and dispersed during early Miocene to the Atlantic forest. The two Atlantic forest clades of Adelophryne started to diversify some 7 Ma minimum, while the northern Amazonian Adelophryne diversified much earlier, some 13 Ma minimum. This striking biogeographic pattern coincides with

  12. S-Nitrosylation-Mediated Redox Transcriptional Switch Modulates Neurogenesis and Neuronal Cell Death

    Directory of Open Access Journals (Sweden)

    Shu-ichi Okamoto

    2014-07-01

    Full Text Available Redox-mediated posttranslational modifications represent a molecular switch that controls major mechanisms of cell function. Nitric oxide (NO can mediate redox reactions via S-nitrosylation, representing transfer of an NO group to a critical protein thiol. NO is known to modulate neurogenesis and neuronal survival in various brain regions in disparate neurodegenerative conditions. However, a unifying molecular mechanism linking these phenomena remains unknown. Here, we report that S-nitrosylation of myocyte enhancer factor 2 (MEF2 transcription factors acts as a redox switch to inhibit both neurogenesis and neuronal survival. Structure-based analysis reveals that MEF2 dimerization creates a pocket, facilitating S-nitrosylation at an evolutionally conserved cysteine residue in the DNA binding domain. S-Nitrosylation disrupts MEF2-DNA binding and transcriptional activity, leading to impaired neurogenesis and survival in vitro and in vivo. Our data define a molecular switch whereby redox-mediated posttranslational modification controls both neurogenesis and neurodegeneration via a single transcriptional signaling cascade.

  13. Latching micro optical switch

    Science.gov (United States)

    Garcia, Ernest J; Polosky, Marc A

    2013-05-21

    An optical switch reliably maintains its on or off state even when subjected to environments where the switch is bumped or otherwise moved. In addition, the optical switch maintains its on or off state indefinitely without requiring external power. External power is used only to transition the switch from one state to the other. The optical switch is configured with a fixed optical fiber and a movable optical fiber. The movable optical fiber is guided by various actuators in conjunction with a latching mechanism that configure the switch in one position that corresponds to the on state and in another position that corresponds to the off state.

  14. Deconstruction of the Ras switching cycle through saturation mutagenesis

    Science.gov (United States)

    Bandaru, Pradeep; Shah, Neel H; Bhattacharyya, Moitrayee; Barton, John P; Kondo, Yasushi; Cofsky, Joshua C; Gee, Christine L; Chakraborty, Arup K; Kortemme, Tanja; Ranganathan, Rama; Kuriyan, John

    2017-01-01

    Ras proteins are highly conserved signaling molecules that exhibit regulated, nucleotide-dependent switching between active and inactive states. The high conservation of Ras requires mechanistic explanation, especially given the general mutational tolerance of proteins. Here, we use deep mutational scanning, biochemical analysis and molecular simulations to understand constraints on Ras sequence. Ras exhibits global sensitivity to mutation when regulated by a GTPase activating protein and a nucleotide exchange factor. Removing the regulators shifts the distribution of mutational effects to be largely neutral, and reveals hotspots of activating mutations in residues that restrain Ras dynamics and promote the inactive state. Evolutionary analysis, combined with structural and mutational data, argue that Ras has co-evolved with its regulators in the vertebrate lineage. Overall, our results show that sequence conservation in Ras depends strongly on the biochemical network in which it operates, providing a framework for understanding the origin of global selection pressures on proteins. DOI: http://dx.doi.org/10.7554/eLife.27810.001 PMID:28686159

  15. Photo- and electro-chromic organometallics with dithienylethene (DTE) linker, L2CpM-DTE-MCpL2: dually stimuli-responsive molecular switch.

    Science.gov (United States)

    Motoyama, Keiko; Li, Huifang; Koike, Takashi; Hatakeyama, Makoto; Yokojima, Satoshi; Nakamura, Shinichiro; Akita, Munetaka

    2011-10-28

    Photochromic dithienylethene (DTE) derivatives, M-DTE-M (M: M(η(5)-C(5)R(5))L(2); M = Fe, Ru; R = H, Me; L = CO, phosphine), with direct σ-bonded, redox-active organometallic attachments are prepared and their response to photo- and electro-chemical stimuli as well as wire-like and switching performance has been investigated. These properties turn out to be dependent on the metal and the auxiliary ligands. The DTE complexes with the MCp(CO)(2) and RuCp(CO)(PPh(3)) fragments undergo reversible photochemical ring-closing and -opening of the DTE moiety upon UV and visible-light irradiation, respectively, whereas the other FeCp(CO)(PPh(3)) and Fe(η(5)-C(5)R(5))(dppe) derivatives are virtually inert with respect to the photochemical ring closing process. Electrochemical analysis of the DTE complexes reveals that 2e-oxidation of the open isomer O also brings about the ring closure of the DTE moiety to afford the Fischer-carbene-type, dicationic closed derivatives C(2+) with the π-conjugated system different from that in the neutral ones C obtained photochemically. Subsequent reduction of C(2+) furnishes the neutral closed species C. Thus the ring closure is mediated not only by the conventional photochemical process but also by the sequential oxidation-reduction process, i.e. the organometallic DTE complexes are found to be dually photo- and electro-chromic. It is notable that the oxidative procedures are viable for the photochemically inert derivatives. Wire-like and switching performance has been evaluated on the basis of the comproportionation constant K(C) for the 1e-oxidized mixed valence monocationic species obtained by the electrochemical analysis and the switching factor SF (K(C)(C)/K(C)(O)), respectively. The K(C)(C) (7.5 × 10(4)) and SF values (5.4 × 10(3)) for phosphine-substituted derivatives are significantly large, as a result of the distinct π-conjugated systems of the DTE moieties involved in the O- (with cross-conjugation) and C-forms (fully

  16. Metabolite profiles of essential oils and molecular markers analysis to explore the biodiversity of Ferula communis: Towards conservation of the endemic giant fennel.

    Science.gov (United States)

    Rahali, Fatma Zohra; Lamine, Myriam; Gargouri, Mahmoud; Rebey, Iness Bettaieb; Hammami, Majdi; Sellami, Ibtissem Hamrouni

    2016-04-01

    in situ conservation. The analysis of chemical constitution of oil of the populations from a specific region revealed predominance of specific constituents indicating possibility of their collection/selection for specific end uses like phytomedicines. Sufficient molecular and biochemical diversity detected among natural populations of this species will form the basis for the future improvement. The correlation between matrices of RAPD and essential oils was not significant. The conservation strategies of populations should be made according to their level of genetic and chemical diversity in relation to geographic location of populations. Our results give some insights into the characterization of this as yet little investigated plant.

  17. Switching off and exchanging of electricity guzzlers. The automotive and suppliers industrie reduce the consumption of energy and materials by means of smart conservation technologies; Stromfresser abschalten und auswechseln. Mit cleveren Spartechniken reduziert die Automobil- und Zulieferindustrie Energie- und Materialverbraeuche

    Energy Technology Data Exchange (ETDEWEB)

    Schroeter, Stefan

    2013-05-21

    New manufacturing methods and manufacturing techniques can reduce the energy consumption and material consumption in the automotive industry and its suppliers clearly. An optimization of established manufacturing processes may be useful. However, the biggest conservations are possible if the production process is completely rethought.

  18. Optical packet switched networks

    DEFF Research Database (Denmark)

    Hansen, Peter Bukhave

    1999-01-01

    Optical packet switched networks are investigated with emphasis on the performance of the packet switch blocks. Initially, the network context of the optical packet switched network is described showing that a packet network will provide transparency, flexibility and bridge the granularity gap...... between the electrical switched layer and the WDM transport layer. Analytical models are implemented to determine the signal quality ghrough the switch blocks in terms of power penalty and to assess the traffic performance of different switch block architectures. Further, a computer simulation model...... is used to investigate the influence on the traffic performance of asynchronous operation of the switch blocks. The signal quality investigation illustrates some of the component requirements in respect to gain saturation in SOA gates and crosstalk in order to obtain high cascadability of the switch...

  19. Remote switch actuator

    Science.gov (United States)

    Haas, Edwin Gerard; Beauman, Ronald; Palo, Jr., Stefan

    2013-01-29

    The invention provides a device and method for actuating electrical switches remotely. The device is removably attached to the switch and is actuated through the transfer of a user's force. The user is able to remain physically removed from the switch site obviating need for protective equipment. The device and method allow rapid, safe actuation of high-voltage or high-current carrying electrical switches or circuit breakers.

  20. Perancangan Switch Matrik Besar Menggunakan Array Switch Analog Zarlink

    OpenAIRE

    2009-01-01

    Secara tradisional, perancangan sebuah switch matrik yang besar dilakukan dengan menggunakan switch-switch elektromekanik. Dengan demikian, banyak bagian yang bergerak yang digunakan untuk membangun switch matrik ini. Dengan kemajuan bidang elektronik, switch elektromekanik saat ini dapat digantikan dengan switch-switch semikonduktor yang ekivalen yang menawarkan solusi yang lebih ekonomis dan memiliki keandalan yang lebih baik. Rumpun switch crosspoint analog Zarlink dapat disusun dengan mud...

  1. CLASP1, astrin and Kif2b form a molecular switch that regulates kinetochore-microtubule dynamics to promote mitotic progression and fidelity.

    Science.gov (United States)

    Manning, Amity L; Bakhoum, Samuel F; Maffini, Stefano; Correia-Melo, Clara; Maiato, Helder; Compton, Duane A

    2010-10-20

    Accurate chromosome segregation during mitosis requires precise coordination of various processes, such as chromosome alignment, maturation of proper kinetochore-microtubule (kMT) attachments, correction of erroneous attachments, and silencing of the spindle assembly checkpoint (SAC). How these fundamental aspects of mitosis are coordinately and temporally regulated is poorly understood. In this study, we show that the temporal regulation of kMT attachments by CLASP1, astrin and Kif2b is central to mitotic progression and chromosome segregation fidelity. In early mitosis, a Kif2b-CLASP1 complex is recruited to kinetochores to promote chromosome movement, kMT turnover, correction of attachment errors, and maintenance of SAC signalling. However, during metaphase, this complex is replaced by an astrin-CLASP1 complex, which promotes kMT stability, chromosome alignment, and silencing of the SAC. We show that these two complexes are differentially recruited to kinetochores and are mutually exclusive. We also show that other kinetochore proteins, such as Kif18a, affect kMT attachments and chromosome movement through these proteins. Thus, CLASP1-astrin-Kif2b complex act as a central switch at kinetochores that defines mitotic progression and promotes fidelity by temporally regulating kMT attachments.

  2. Molecular and functional characterization of a CS1 (CRACC) splice variant expressed in human NK cells that does not contain immunoreceptor tyrosine-based switch motifs.

    Science.gov (United States)

    Lee, Jae Kyung; Boles, Kent S; Mathew, Porunelloor A

    2004-10-01

    CS1 (CRACC, novel Ly9) is a novel member of the CD2 family expressed on natural killer (NK), T and stimulated B cells. Although the cytoplasmic domain of CS1 contains immunoreceptor tyrosine-based switch motifs (ITSM), which enables to recruite signaling lymphocyte activation molecule (SLAM)-associated protein (SAP/SH2D1A), it activates NK cells in the absence of a functional SAP. CS1 is a self ligand and homophilic interaction of CS1 regulates NK cell cytolytic activity. Here we have identified a novel splice variant of CS1 (CS1-S), which lacks ITSM. Human NK cells express mRNA for both wild-type CS1 (CS1-L) and CS1-S and their expression level remained steady upon various stimulations. To determine the function of each isoform, cDNA for CS1-L and CS1-S were transfected into the rat NK cell line RNK-16 and functionally tested using redirected cytotoxicity assays and calcium flux experiments. CS1-L was able to mediate redirected cytotoxicity of P815 target cells in the presence of monoclonal antibody against CS1 and a rise in intracellular calcium within RNK-16 cells, suggesting that CS1-L is an activating receptor, whereas CS1-S showed no effects. Interestingly, SAP associated with unstimulated CS1-L and dissociated upon pervanadate stimulation. These results indicate that CS1-L and CS1-S may differentially regulate human NK cell functions.

  3. VEGFR2 Functions As an H2S-Targeting Receptor Protein Kinase with Its Novel Cys1045–Cys1024 Disulfide Bond Serving As a Specific Molecular Switch for Hydrogen Sulfide Actions in Vascular Endothelial Cells

    Science.gov (United States)

    Tao, Bei-Bei; Liu, Shu-Yuan; Zhang, Cai-Cai; Fu, Wei; Cai, Wen-Jie; Wang, Yi; Shen, Qing; Wang, Ming-Jie; Chen, Ying; Zhang, Li-Jia; Zhu, Yi-Zhun

    2013-01-01

    Abstract Aims: The potential receptor for hydrogen sulfide (H2S) remains unknown. Results: H2S could directly activate vascular endothelial growth factor receptor 2 (VEGFR2) and that a small interfering RNA (siRNA)-mediated knockdown of VEGFR2 inhibited H2S-induced migration of human vascular endothelial cells. H2S promoted angiogenesis in Matrigel plug assay in mice and this effect was attenuated by a VEGF receptor inhibitor. Using tandem mass spectrometry (MS), we identified a new disulfide complex located between Cys1045 and Cys1024 within VEGFR2 that was labile to H2S-mediated modification. Kinase activity of the mutant VEGFR2 (C1045A) devoid of the Cys1045–Cys1024 disulfide bond was significantly higher than wild-type VEGFR2. Transfection with vectors expressing VEGFR2 (C1045A) caused a significant increase in cell migration, while the migration-promoting effect of H2S disappeared in the cells transfected with VEGFR2 (C1045A). Therefore, the Cys1045–Cys1024 disulfide bond serves as an intrinsic inhibitory motif and functions as a molecular switch for H2S. The formation of the Cys1045–Cys1024 disulfide bond disrupted the integrity of the active conformation of VEGFR2. Breaking the Cys1045–Cys1024 disulfide bond recovered the active conformation of VEGFR2. This motif was prone to a nucleophilic attack by H2S via an interaction of their frontier molecular orbitals. siRNA-mediated knockdown of cystathionine γ-lyase attenuated migration of vascular endothelial cells induced by VEGF or moderate hypoxia. Innovation and Conclusion: The study provides the first piece of evidence of a molecular switch in H2S-targeting receptor protein kinase in H2S-induced angiogenesis and that may be applicable to additional kinases containing functionally important disulfide bonds in mediating various H2S actions. Antioxid. Redox Signal. 19, 448–464. PMID:23199280

  4. Multi-Functional Molecular Switches Based on Photochromic Dithienylethenes%多功能二噻吩乙烯光致变色光分子开关材料

    Institute of Scientific and Technical Information of China (English)

    邹祺; 张隽佶; 田禾

    2012-01-01

    光致变色材料是一类在不同波长的光交替照射下,产生两种可进行可逆转换的光致异构体并伴随明显的光物理和光化学性能变化的材料。基于其特殊的光致异构性质,人们已开发出多种光致变色功能材料并将其广泛应用于超高密度光信息存储、分子开关、分子逻辑门、分子导线、光电材料、多光子器件、表面/纳米器件、液晶材料、化学传感、生物成像、自组装、聚集诱导发光、光控生物体系等诸多领域。其中,二噻吩乙烯类化合物因其出色的热稳定性、优良的耐疲劳性、快的响应速率、高的转化率和量子产率以及出色的固相反应活性而成为理想的光致变色材料之一。本文主要围绕近期本研究组研究成果着重介绍近几年二噻吩乙烯类化合物从溶液体系到功能化表面体系的研究进展,探讨当前该领域存在的问题并对其前景和发展方向进行展望。%Photochromic materials are those which can undergo reversible photo-switches between two different states or isomers upon alternative irradiation with different wavelengths of light accompanied by distinct photophysieal and photochemical properties. Inspired by their special photo-switchable characteristics, a variety of light-driven functional materials have been exploited, such as ultrahigh-density optical data storage, molecular switches, logic gates, molecular wires, optic/electronic devices, multi-photon devices, surfaee/nanopartiele devices, liquid crystals, bio-imaging and so on. Apart from these, further creation of optoelectronic and photo- optical devices based on photochromic molecular switches which operate at both molecular and supramoleeular levels have recently attracted many attentions. Thus photo-switchable compounds also have played an important role in sensing, self-assembly, aggregation-induced enhanced emission and photo-controlled biological systems. In particular

  5. Molecular cloning of a highly conserved mouse and human integral membrane protein (Itm1) and genetic mapping to mouse chromosome 9

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Guizhu; Tylzanowski, P. [Univ. of Antwerp (Belgium); Deleersnijder, W. [N.V. Innogenetics, Ghent (Belgium)] [and others

    1996-02-01

    We have isolated and characterized a novel cDNA coding for a highly hydrophobic protein (B5) from a fetal mouse mandibular condyle cDNA library. The full-length mouse B5 cDNA is 3095 nucleotides long and contains a potential open reading frame coding for a protein of 705 amino acids with a calculated molecular weight of 80.5 kDa. The B5 mRNA is differentially polyadenylated, with the most abundant transcript having a length of 2.7 kb. The human homolog of B5 was isolated from a cDNA testis library. The predicted amino acid sequence of the human B5 is 98.5% identical to that of mouse. The most striking feature of the B5 protein is the presence of numerous (10-14) potential transmembrane domains, characteristic of an integral membrane protein. Similarity searches in public databanks reveal that B5 is 58% similar to the T12A2.2 gene of Caenorhabditis elegans and 60% similar to the STT3 gene of Saccharomyces cerevisiae. Futhermore, the report of an EST sequence (Accession No. Z13858) related to the human B5, but identical to the STT3 gene, indicates that B5 belongs to a larger gene family coding for novel putative transmembrane proteins. This family exhibits a remarkable degree of conservation in different species. The gene for B5, designated Itm1 (Integral membrane protein 1), is located on mouse chromosome 9. 28 refs., 4 figs.

  6. Design of two-layer switching rule for stabilization of switched linear systems with mismatched switching

    Institute of Scientific and Technical Information of China (English)

    Dan MA

    2014-01-01

    A two-layer switching architecture and a two-layer switching rule for stabilization of switched linear control systems are proposed, under which the mismatched switching between switched systems and their candidate hybrid controllers can be allowed. In the low layer, a state-dependent switching rule with a dwell time constraint to exponentially stabilize switched linear systems is given;in the high layer, supervisory conditions on the mismatched switching frequency and the mismatched switching ratio are presented, under which the closed-loop switched system is still exponentially stable in case of the candidate controller switches delay with respect to the subsystems. Different from the traditional switching rule, the two-layer switching architecture and switching rule have robustness, which in some extend permit mismatched switching between switched subsystems and their candidate controllers.

  7. Orbital order switching in molecular calculations using GGA functionals: Qualitative errors in materials modeling for electrochemical power sources and how to fix them

    Science.gov (United States)

    Sk, Mahasin Alam; Chen, Yingqian; Manzhos, Sergei

    2016-08-01

    We report a qualitative difference in molecular band structures and frontier orbital nodal structures in DFT calculations using GGA vs. hybrid functionals and Hartree Fock in molecules used in electrochemical power sources. This can have a significant effect in applications sensitive to redox potentials and to orbital overlaps (excitations, electron transfer rates) but for which the use of hybrid functionals is impractical, such as solids or interfaces used in electrochemical energy conversion and storage technologies. We show that correct band structures and nodal structures (ordering) of frontier orbitals can be obtained by applying a Hubbard correction to selected atomic states.

  8. Blue to near-IR energy transfer cascade within a dye-doped polymer matrix, mediated by a photochromic molecular switch.

    Science.gov (United States)

    Dryza, Viktoras; Smith, Trevor A; Bieske, Evan J

    2016-02-21

    The spectroscopic properties of a poly(methyl methacrylate) matrix doped with a coumarin dye, a cyanine dye, and a photochromic spiropyran dye have been investigated. Before UV irradiation of the matrix, excitation of the coumarin dye results in minimal energy transfer to the cyanine dye. The energy transfer is substantially enhanced following UV irradiation of the matrix, which converts the colourless spiropyran isomer to the coloured merocyanine isomer, which then acts as an intermediate bridge by accepting energy from the coumarin dye and then donating energy to the cyanine dye. This demonstration of a switchable energy transfer cascade should help initiate new research directions in molecular photonics.

  9. Conservative management.

    Science.gov (United States)

    Kruis, W; Leifeld, L; Pfützer, R

    2012-01-01

    Treatment of diverticulitis comprises at least two options: conservative or surgical management. There is a recent trend to limit surgical treatment of acute diverticulitis and to favor conservative management. This review addresses general aspects of conservative patient care with special focus on the treatment of patients with a first attack of diverticulitis. The presentation does not include a discussion of specific drugs which is given in other sections of this issue.

  10. Conserved patterns of axogenesis in the panarthropod brain.

    Science.gov (United States)

    Boyan, George; Williams, Leslie; Liu, Yu

    2015-03-01

    Neuropils in the cerebral midline of Panarthropoda exhibit a wide spectrum of neuroarchitectures--from rudimentary to highly elaborated--and which at first sight defy a unifying neuroarchitectural principle. Developmental approaches have shown that in model arthropods such as insects, conserved cellular and molecular mechanisms first establish a simple axon scaffold in the brain. However, to be adapted for adult life, this immature ground plan is transformed by a developmental process--known in the grasshopper as "fascicle switching"--in which subsets of neurons systematically redirect their growth cones at stereotypic locations across the brain midline. A topographic system of choice points along the transverse brain axis where axons decussate features in all panarthropods studied even though different modes of neurogenesis and varying degrees of neuropilar elaboration are involved. This suggests that the molecular mechanisms regulating choice point selection may be conserved. In combination with recent cladistic interpretations of arthropod phylogeny based on nuclear protein-coding sequences the data argue for this topographic decussation as having evolved early and being a conserved feature of the Panarthropoda. Differences in elaboration likely reflect both the extent to which neuropilar reorganization has progressed during development and the lifestyle of the individual organism. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Resonance Energy Transfer-Based Molecular Switch Designed Using a Systematic Design Process Based on Monte Carlo Methods and Markov Chains

    Science.gov (United States)

    Rallapalli, Arjun

    A RET network consists of a network of photo-active molecules called chromophores that can participate in inter-molecular energy transfer called resonance energy transfer (RET). RET networks are used in a variety of applications including cryptographic devices, storage systems, light harvesting complexes, biological sensors, and molecular rulers. In this dissertation, we focus on creating a RET device called closed-diffusive exciton valve (C-DEV) in which the input to output transfer function is controlled by an external energy source, similar to a semiconductor transistor like the MOSFET. Due to their biocompatibility, molecular devices like the C-DEVs can be used to introduce computing power in biological, organic, and aqueous environments such as living cells. Furthermore, the underlying physics in RET devices are stochastic in nature, making them suitable for stochastic computing in which true random distribution generation is critical. In order to determine a valid configuration of chromophores for the C-DEV, we developed a systematic process based on user-guided design space pruning techniques and built-in simulation tools. We show that our C-DEV is 15x better than C-DEVs designed using ad hoc methods that rely on limited data from prior experiments. We also show ways in which the C-DEV can be improved further and how different varieties of C-DEVs can be combined to form more complex logic circuits. Moreover, the systematic design process can be used to search for valid chromophore network configurations for a variety of RET applications. We also describe a feasibility study for a technique used to control the orientation of chromophores attached to DNA. Being able to control the orientation can expand the design space for RET networks because it provides another parameter to tune their collective behavior. While results showed limited control over orientation, the analysis required the development of a mathematical model that can be used to determine the

  12. Saturated Switching Systems

    CERN Document Server

    Benzaouia, Abdellah

    2012-01-01

    Saturated Switching Systems treats the problem of actuator saturation, inherent in all dynamical systems by using two approaches: positive invariance in which the controller is designed to work within a region of non-saturating linear behaviour; and saturation technique which allows saturation but guarantees asymptotic stability. The results obtained are extended from the linear systems in which they were first developed to switching systems with uncertainties, 2D switching systems, switching systems with Markovian jumping and switching systems of the Takagi-Sugeno type. The text represents a thoroughly referenced distillation of results obtained in this field during the last decade. The selected tool for analysis and design of stabilizing controllers is based on multiple Lyapunov functions and linear matrix inequalities. All the results are illustrated with numerical examples and figures many of them being modelled using MATLAB®. Saturated Switching Systems will be of interest to academic researchers in con...

  13. Single Atom Plasmonic Switch

    OpenAIRE

    Emboras, Alexandros; Niegemann, Jens; Ma, Ping; Haffner, Christian; Luisier, Mathieu; Hafner, Christian; Schimmel, Thomas; Leuthold, Juerg

    2015-01-01

    The atom sets an ultimate scaling limit to Moores law in the electronics industry. And while electronics research already explores atomic scales devices, photonics research still deals with devices at the micrometer scale. Here we demonstrate that photonic scaling-similar to electronics-is only limited by the atom. More precisely, we introduce an electrically controlled single atom plasmonic switch. The switch allows for fast and reproducible switching by means of the relocation of an individ...

  14. Atomic Scale Plasmonic Switch

    OpenAIRE

    Emboras, A.; Niegemann, J.; Ma, P.; Haffner, C; Pedersen, A.; Luisier, M.; Hafner, C.; Schimmel, T.; Leuthold, J.

    2016-01-01

    The atom sets an ultimate scaling limit to Moore’s law in the electronics industry. While electronics research already explores atomic scales devices, photonics research still deals with devices at the micrometer scale. Here we demonstrate that photonic scaling, similar to electronics, is only limited by the atom. More precisely, we introduce an electrically controlled plasmonic switch operating at the atomic scale. The switch allows for fast and reproducible switching by means of the relocat...

  15. FreeSWITCH Cookbook

    CERN Document Server

    Minessale, Anthony

    2012-01-01

    This is a problem-solution approach to take your FreeSWITCH skills to the next level, where everything is explained in a practical way. If you are a system administrator, hobbyist, or someone who uses FreeSWITCH on a regular basis, this book is for you. Whether you are a FreeSWITCH expert or just getting started, this book will take your skills to the next level.

  16. Encryption Switching Protocols

    OpenAIRE

    Couteau, Geoffroy; Peters, Thomas; Pointcheval, David

    2016-01-01

    International audience; We formally define the primitive of encryption switching protocol (ESP), allowing to switch between two encryption schemes. Intuitively, this two-party protocol converts given ciphertexts from one scheme into ciphertexts of the same messages under the other scheme, for any polynomial number of switches, in any direction. Although ESP is a special kind of two-party computation protocol, it turns out that ESP implies general two-party computation (2-PC) under natural con...

  17. Switching to nilotinib in patients with chronic myeloid leukemia in chronic phase with molecular suboptimal response to frontline imatinib: SENSOR final results and BIM polymorphism substudy.

    Science.gov (United States)

    Miyamura, Koichi; Miyamoto, Toshihiro; Tanimoto, Mitsune; Yamamoto, Kazuhito; Kimura, Shinya; Kawaguchi, Tatsuya; Matsumura, Itaru; Hata, Tomoko; Tsurumi, Hisashi; Saito, Shigeki; Hino, Masayuki; Tadokoro, Seiji; Meguro, Kuniaki; Hyodo, Hideo; Yamamoto, Masahide; Kubo, Kohmei; Tsukada, Junichi; Kondo, Midori; Aoki, Makoto; Okada, Hikaru; Yanada, Masamitsu; Ohyashiki, Kazuma; Taniwaki, Masafumi

    2016-12-01

    Optimal management of patients with chronic myeloid leukemia in chronic phase with suboptimal molecular response (MR) to frontline imatinib is undefined. We report final results from SENSOR, which evaluated efficacy/safety of nilotinib in this setting. A substudy assessed whether BIM polymorphisms impacted response to nilotinib. In this single-arm, multicenter study, Japanese patients with suboptimal MR per European LeukemiaNet 2009 criteria (complete cytogenetic response, but not major MR [MMR]) after ≥18 months of frontline imatinib received nilotinib 400mg twice daily for 24 months. MR, BCR-ABL1 mutations/variants, and BIM polymorphisms were evaluated in a central laboratory. Primary endpoint was the MMR rate at 12 months (null hypothesis of 40%). Of 45 patients (median exposure, 22.08 months), 39 completed the study and six discontinued. At 12 and 24 months, 51.1% (95% CI, 35.8%-66.3%) and 66.7% (95% CI, 51.0%-80.0%) achieved MMR, respectively. Cumulative MMR incidence by 24 months was 75.6%. Of 40 patients analyzed, 10 of 12 (83.3%) with and 17 of 28 (60.7%) without BIM polymorphisms achieved MMR at 24 months. The safety profile was manageable with dose reductions and interruptions. Nilotinib provided clinical benefit for patients with suboptimal response to imatinib, and BIM polymorphisms did not influence MMR achievement. ClinicalTrials.gov: NCT01043874.

  18. Platform switching and bone platform switching.

    Science.gov (United States)

    Carinci, Francesco; Brunelli, Giorgio; Danza, Matteo

    2009-01-01

    Bone platform switching involves an inward bone ring in the coronal part of the implant that is in continuity with the alveolar bone crest. Bone platform switching is obtained by using a dental fixture with a reverse conical neck. A retrospective study was performed to evaluate the effectiveness of conventional vs reverse conical neck implants. In the period between May 2004 and November 2007, 86 patients (55 females and 31 males; median age, 53 years) were operated and 234 implants were inserted: 40 and 194 were conventional vs reverse conical neck implants, respectively. Kaplan-Meier algorithm and Cox regression were used to detect those variables associated with the clinical outcome. No differences in survival and success rates were detected between conventional vs reverse conical neck implants alone or in combination with any of the studied variables. Although bone platform switching leads to several advantages, no statistical difference in alveolar crest resorption is detected in comparison with reverse conical neck implants. We suppose that the proximity of the implant abutment junction to the alveolar crestal bone gives no protection against the microflora contained in the micrograph. Additional studies on larger series and a combination of platform switching and bone platform switching could lead to improved clinical outcomes.

  19. Emergence of phenotype switching through continuous and discontinuous evolutionary transitions

    Science.gov (United States)

    Patra, Pintu; Klumpp, Stefan

    2015-07-01

    Bacterial persistence (phenotypic tolerance to antibiotics) provides a prime example of bet-hedging, where normally growing cells generate slow-growing but antibiotic-tolerant persister cells to survive through periods of exposure to antibiotics. The population dynamics of persistence is explained by a phenotype switching mechanism that allows individual cells to switch between these different cellular states with different environmental sensitivities. Here, we perform a theoretical study based on an exact solution for the case of a periodic variation of the environment to address how phenotype switching emerges and under what conditions switching is or is not beneficial for long-time growth. Specifically we report a bifurcation through which a fitness maximum and minimum emerge above a threshold in the duration of exposure to the antibiotic. Only above this threshold, the optimal phenotype switching rates are adjusted to the time scales of the environment, as emphasized by previous theoretical studies, while below the threshold a non-switching population is fitter than a switching one. The bifurcation can be of different type, depending on how the phenotype switching rates are allowed to vary. If the switching rates for both directions of the switch are coupled, the transition is discontinuous and results in evolutionary hysteresis, which we confirm with a stochastic simulation. If the switching rates vary individually, a continuous transition is obtained and no hysteresis is found. We discuss how both scenarios can be linked to changes in the underlying molecular networks.

  20. Reshaping conservation

    DEFF Research Database (Denmark)

    Funder, Mikkel; Danielsen, Finn; Ngaga, Yonika

    2013-01-01

    members strengthen the monitoring practices to their advantage, and to some extent move them beyond the reach of government agencies and conservation and development practitioners. This has led to outcomes that are of greater social and strategic value to communities than the original 'planned' benefits......, although the monitoring scheme has also to some extent become dominated by local 'conservation elites' who negotiate the terrain between the state and other community members. Our findings suggest that we need to move beyond simplistic assumptions of community strategies and incentives in participatory...... conservation and allow for more adaptive and politically explicit governance spaces in protected area management....

  1. Light-Induced Switching of Tunable Single-Molecule Junctions

    KAUST Repository

    Sendler, Torsten

    2015-04-16

    A major goal of molecular electronics is the development and implementation of devices such as single-molecular switches. Here, measurements are presented that show the controlled in situ switching of diarylethene molecules from their nonconductive to conductive state in contact to gold nanoelectrodes via controlled light irradiation. Both the conductance and the quantum yield for switching of these molecules are within a range making the molecules suitable for actual devices. The conductance of the molecular junctions in the opened and closed states is characterized and the molecular level E 0, which dominates the current transport in the closed state, and its level broadening Γ are identified. The obtained results show a clear light-induced ring forming isomerization of the single-molecule junctions. Electron withdrawing side-groups lead to a reduction of conductance, but do not influence the efficiency of the switching mechanism. Quantum chemical calculations of the light-induced switching processes correlate these observations with the fundamentally different low-lying electronic states of the opened and closed forms and their comparably small modification by electron-withdrawing substituents. This full characterization of a molecular switch operated in a molecular junction is an important step toward the development of real molecular electronics devices.

  2. In control of switching, motion, and organization

    NARCIS (Netherlands)

    Feringa, B.L.; Delden, R.A.van; Ter Wiel, M.K.J.

    2003-01-01

    Nature's solutions to control organization, switching, and linear and rotary motion are not only extremely elegant, but fascinating if one considers the design and synthesis of artificial molecular systems with such functions in order to add components to the nanotool-box. The synthesis of chiroptic

  3. Optimal switching using coherent control

    DEFF Research Database (Denmark)

    Kristensen, Philip Trøst; Heuck, Mikkel; Mørk, Jesper

    2013-01-01

    that the switching time, in general, is not limited by the cavity lifetime. Therefore, the total energy required for switching is a more relevant figure of merit than the switching speed, and for a particular two-pulse switching scheme we use calculus of variations to optimize the switching in terms of input energy....

  4. Conservation of toll-like receptor signaling pathways in teleost fish

    Science.gov (United States)

    Purcell, M.K.; Smith, K.D.; Aderem, A.; Hood, L.; Winton, J.R.; Roach, J.C.

    2006-01-01

    In mammals, toll-like receptors (TLR) recognize ligands, including pathogen-associated molecular patterns (PAMPs), and respond with ligand-specific induction of genes. In this study, we establish evolutionary conservation in teleost fish of key components of the TLR-signaling pathway that act as switches for differential gene induction, including MYD88, TIRAP, TRIF, TRAF6, IRF3, and IRF7. We further explore this conservation with a molecular phylogenetic analysis of MYD88. To the extent that current genomic analysis can establish, each vertebrate has one ortholog to each of these genes. For molecular tree construction and phylogeny inference, we demonstrate a methodology for including genes with only partial primary sequences without disrupting the topology provided by the high-confidence full-length sequences. Conservation of the TLR-signaling molecules suggests that the basic program of gene regulation by the TLR-signaling pathway is conserved across vertebrates. To test this hypothesis, leukocytes from a model fish, rainbow trout (Oncorhynchus mykiss), were stimulated with known mammalian TLR agonists including: Diacylated and triacylated forms of lipoprotein, flagellin, two forms of LPS, synthetic double-stranded RNA, and two imidazoquinoline compounds (loxoribine and R848). Trout leukocytes responded in vitro to a number of these agonists with distinct patterns of cytokine expression that correspond to mammalian responses. Our results support the key prediction from our phylogenetic analyses that strong selective pressure of pathogenic microbes has preserved both TLR recognition and signaling functions during vertebrate evolution. ?? 2005 Elsevier Inc. All rights reserved.

  5. Mode Initialization when Simulating Switched Bond Graphs

    OpenAIRE

    Edström, Krister

    1997-01-01

    When simulating hybrid systems using switched bond graphs, the initialization of new modes is made by using a generalization of the principle of momentum conservation. Here it is shown how to use causality propagation to get an efficient initialization algorithm. By looking at causal paths, set of variables that have to be initialized simultaneously are found. Furthermore, it is shown how impulses due to structural changes in the system can be found with a correct initialization and with a co...

  6. Wildlife Conservation

    OpenAIRE

    Clive L. Spash; Aldred, Jonathan

    1998-01-01

    In this paper we consider how conservation has arisen as a key aspect of the reaction to human-initiated degradation and disappearance of ecosystems, wild lands. and wildlife. Concern over species extinction is given an historical perspective which shows the way in which pressure on wild and natural aspects of global ecology have changed in recent centuries. The role of conservation in the struggle to protect the environment is then analysed using underlying ethical arguments behind the econo...

  7. Identification of a Conserved 8 aa Insert in the PIP5K Protein in the Saccharomycetaceae family of Fungi and the Molecular Dynamics Simulations and Structural Analysis to investigate its Potential Functional Role.

    Science.gov (United States)

    Khadka, Bijendra; Gupta, Radhey S

    2017-04-13

    Homologs of the phosphatidylinositol-4-phosphate-5-kinase (PIP5K), which controls a multitude of essential cellular functions, contain a 8 aa insert in a conserved region that is specific for the Saccharomycetaceae family of fungi. Using structures of human PIP4K proteins as templates, structural models were generated of the Saccharomyces cerevisiae and human PIP5K proteins. In the modeled S. cerevisiae PIP5K, the 8 aa insert forms a surface exposed loop, present on the same face of the protein as the activation loop of the kinase domain. Electrostatic potential analysis indicates that the residues from 8 aa conserved loop form a highly-positively charged surface patch, which through electrostatic interaction with the anionic portions of phospholipid head groups, is expected to play a role in the membrane interaction of the yeast PIP5K. To unravel this prediction, molecular dynamics (MD) simulations were carried out to examine the binding interaction of PIP5K, either containing or lacking the conserved signature insert (CSI), with two different membrane lipid bilayers. The results from MD studies provide insights concerning the mechanistic of interaction of PIP5K with lipid bilayer, and support the contention that the identified 8 aa conserved insert in fungal PIP5K plays an important role in the binding of this protein with membrane surface. This article is protected by copyright. All rights reserved.

  8. Optical switching device

    NARCIS (Netherlands)

    Broeder, F.J.A. den; Hanzen, R.M.N.; Duine, P.A.; Jungblut, R.M.; Draijer, C.; Roozeboom, F.; Sluis, P. van der

    2000-01-01

    A description is given of an optical switching device (1) comprising a transparent substrate (3), a switching film (5) of a hydride compound of a trivalent transition or rare earth metal having a thickness of 300 nm, and a palladium capping layer (7) having a thickness of 30 nm. The capping layer is

  9. Quantum cryptography without switching.

    Science.gov (United States)

    Weedbrook, Christian; Lance, Andrew M; Bowen, Warwick P; Symul, Thomas; Ralph, Timothy C; Lam, Ping Koy

    2004-10-22

    We propose a new coherent state quantum key distribution protocol that eliminates the need to randomly switch between measurement bases. This protocol provides significantly higher secret key rates with increased bandwidths than previous schemes that only make single quadrature measurements. It also offers the further advantage of simplicity compared to all previous protocols which, to date, have relied on switching.

  10. Switch on, switch off: stiction in nanoelectromechanical switches

    KAUST Repository

    Wagner, Till J W

    2013-06-13

    We present a theoretical investigation of stiction in nanoscale electromechanical contact switches. We develop a mathematical model to describe the deflection of a cantilever beam in response to both electrostatic and van der Waals forces. Particular focus is given to the question of whether adhesive van der Waals forces cause the cantilever to remain in the \\'ON\\' state even when the electrostatic forces are removed. In contrast to previous studies, our theory accounts for deflections with large slopes (i.e. geometrically nonlinear). We solve the resulting equations numerically to study how a cantilever beam adheres to a rigid electrode: transitions between \\'free\\', \\'pinned\\' and \\'clamped\\' states are shown to be discontinuous and to exhibit significant hysteresis. Our findings are compared to previous results from linearized models and the implications for nanoelectromechanical cantilever switch design are discussed. © 2013 IOP Publishing Ltd.

  11. Single Atom Plasmonic Switch

    CERN Document Server

    Emboras, Alexandros; Ma, Ping; Haffner, Christian; Luisier, Mathieu; Hafner, Christian; Schimmel, Thomas; Leuthold, Juerg

    2015-01-01

    The atom sets an ultimate scaling limit to Moores law in the electronics industry. And while electronics research already explores atomic scales devices, photonics research still deals with devices at the micrometer scale. Here we demonstrate that photonic scaling-similar to electronics-is only limited by the atom. More precisely, we introduce an electrically controlled single atom plasmonic switch. The switch allows for fast and reproducible switching by means of the relocation of an individual or at most - a few atoms in a plasmonic cavity. Depending on the location of the atom either of two distinct plasmonic cavity resonance states are supported. Experimental results show reversible digital optical switching with an extinction ration of 10 dB and operation at room temperature with femtojoule (fJ) power consumption for a single switch operation. This demonstration of a CMOS compatible, integrated quantum device allowing to control photons at the single-atom level opens intriguing perspectives for a fully i...

  12. Optical packet switching

    Science.gov (United States)

    Shekel, Eyal; Ruschin, Shlomo; Majer, Daniel; Levy, Jeff; Matmon, Guy; Koenigsberg, Lisa; Vecht, Jacob; Geron, Amir; Harlavan, Rotem; Shfaram, Harel; Arbel, Arnon; McDermott, Tom; Brewer, Tony

    2005-02-01

    We report here a scalable, multichassis, 6.3 terabit core router, which utilizes our proprietary optical switch. The router is commercially available and deployed in several customer sites. Our solution combines optical switching with electronic routing. An internal optical packet switching network interconnects the router"s electronic line cards, where routing and buffering functions take place electronically. The system architecture and performance will be described. The optical switch is based on Optical Phased Array (OPA) technology. It is a 64 x 64, fully non-blocking, optical crossbar switch, capable of switching in a fraction of a nanosecond. The basic principles of operation will be explained. Loss and crosstalk results will be presented, as well as the results of BER measurements of a 160 Gbps transmission through one channel. Basic principles of operation and measured results will be presented for the burst-mode-receivers, arbitration algorithm and synchronization. Finally, we will present some of our current research work on a next-generation optical switch. The technological issues we have solved in our internal optical packet network can have broad applicability to any global optical packet network.

  13. Conservation endocrinology

    Science.gov (United States)

    McCormick, Stephen; Romero, Michael

    2017-01-01

    Endocrinologists can make significant contributions to conservation biology by helping to understand the mechanisms by which organisms cope with changing environments. Field endocrine techniques have advanced rapidly in recent years and can provide substantial information on the growth, stress, and reproductive status of individual animals, thereby providing insight into current and future responses of populations to changes in the environment. Environmental stressors and reproductive status can be detected nonlethally by measuring a number of endocrine-related endpoints, including steroids in plasma, living and nonliving tissue, urine, and feces. Information on the environmental or endocrine requirements of individual species for normal growth, development, and reproduction will provide critical information for species and ecosystem conservation. For many taxa, basic information on endocrinology is lacking, and advances in conservation endocrinology will require approaches that are both “basic” and “applied” and include integration of laboratory and field approaches.

  14. A Metabolic Switch

    DEFF Research Database (Denmark)

    Hjorth, Poul G.

    Our muscles are metabolically flexible, i.e., they are capable of `switching' between two types of oxidation: (1) when fasting, a predominantly lipid oxidation with high rates of fatty acid uptake, and (2) when fed, suppression of lipid oxidation in favour of increased glucose uptake, oxidation...... and storage, in response to insulin. One of the many manifestations of obesity and Type 2 diabetes is an insulin resistance of the skeletal muscles, which suppresses this metabolic switch. This talk describes recent development of a low-dimensional system of ODEs that model the metabolic switch, displaying...

  15. JUNOS Enterprise Switching

    CERN Document Server

    Reynolds, Harry

    2009-01-01

    JUNOS Enterprise Switching is the only detailed technical book on Juniper Networks' new Ethernet-switching EX product platform. With this book, you'll learn all about the hardware and ASIC design prowess of the EX platform, as well as the JUNOS Software that powers it. Not only is this extremely practical book a useful, hands-on manual to the EX platform, it also makes an excellent study guide for certification exams in the JNTCP enterprise tracks. The authors have based JUNOS Enterprise Switching on their own Juniper training practices and programs, as well as the configuration, maintenanc

  16. Photoconductive switch package

    Science.gov (United States)

    Ca[rasp, George J

    2013-10-22

    A photoconductive switch is formed of a substrate that has a central portion of SiC or other photoconductive material and an outer portion of cvd-diamond or other suitable material surrounding the central portion. Conducting electrodes are formed on opposed sides of the substrate, with the electrodes extending beyond the central portion and the edges of the electrodes lying over the outer portion. Thus any high electric fields produced at the edges of the electrodes lie outside of and do not affect the central portion, which is the active switching element. Light is transmitted through the outer portion to the central portion to actuate the switch.

  17. Electromechanical magnetization switching

    Energy Technology Data Exchange (ETDEWEB)

    Chudnovsky, Eugene M. [Department of Physics and Astronomy, Lehman College and Graduate School, The City University of New York, 250 Bedford Park Boulevard West, Bronx, New York 10468-1589 (United States); Jaafar, Reem [Department of Mathematics, Engineering and Computer Science, LaGuardia Community College, The City University of New York, 31-10 Thomson Avenue, Long Island City, New York 11101 (United States)

    2015-03-14

    We show that the magnetization of a torsional oscillator that, in addition to the magnetic moment also possesses an electrical polarization, can be switched by the electric field that ignites mechanical oscillations at the frequency comparable to the frequency of the ferromagnetic resonance. The 180° switching arises from the spin-rotation coupling and is not prohibited by the different symmetry of the magnetic moment and the electric field as in the case of a stationary magnet. Analytical equations describing the system have been derived and investigated numerically. Phase diagrams showing the range of parameters required for the switching have been obtained.

  18. Conserved water-mediated hydrogen bond network between TM-I, -II, -VI, and -VII in 7TM receptor activation

    DEFF Research Database (Denmark)

    Nygaard, Rie; Hansen, Louise Valentin; Mokrosinski, Jacek;

    2010-01-01

    Five highly conserved polar residues connected by a number of structural water molecules together with two rotamer micro-switches, TrpVI:13 and TyrVII:20, constitute an extended hydrogen bond network between the intracellular segments of TM-I, -II, -VI, and -VII of 7TM receptors. Molecular dynamics...... to apparently function as a catching trap for water molecules. Mutational analysis of the beta2-adrenergic receptor demonstrated that the highly conserved polar residues of the hydrogen bond network were all important for receptor signaling but served different functions, some dampening constitutive activity...... (AsnI:18, AspII:10, and AsnVII:13), whereas others (AsnVII:12 and AsnVII:16) located one helical turn apart and sharing a water molecule were shown to be essential for agonist-induced signaling. It is concluded that the conserved water hydrogen bond network of 7TM receptors constitutes an extended...

  19. Transcriptome reprogramming during developmental switching in Physarum polycephalum involves extensive remodeling of intracellular signaling networks.

    Science.gov (United States)

    Glöckner, Gernot; Marwan, Wolfgang

    2017-09-26

    Activation of a phytochrome photoreceptor triggers a program of Physarum polycephalum plasmodial cell differentiation through which a mitotic multinucleate protoplasmic mass synchronously develops into haploid spores formed by meiosis and rearrangement of cellular components. We have performed a transcriptome-wide RNAseq study of cellular reprogramming and developmental switching. RNAseq analysis revealed extensive remodeling of intracellular signaling and regulation in switching the expression of sets of genes encoding transcription factors, kinases, phosphatases, signal transduction proteins, RNA-binding proteins, ubiquitin ligases, regulators of the mitotic and meiotic cell cycle etc. in conjunction with the regulation of genes encoding metabolic enzymes and cytoskeletal proteins. About 15% of the differentially expressed genes shared similarity with members of the evolutionary conserved set of core developmental genes of social amoebae. Differential expression of genes encoding regulators that act at the transcriptional, translational, and post-translational level indicates the establishment of a new state of cellular function and reveals evolutionary deeply conserved molecular changes involved in cellular reprogramming and differentiation in a prototypical eukaryote.

  20. Conserved signature indels and signature proteins as novel tools for understanding microbial phylogeny and systematics: identification of molecular signatures that are specific for the phytopathogenic genera Dickeya, Pectobacterium and Brenneria.

    Science.gov (United States)

    Naushad, Hafiz Sohail; Lee, Brian; Gupta, Radhey S

    2014-02-01

    Genome sequences are enabling applications of different approaches to more clearly understand microbial phylogeny and systematics. Two of these approaches involve identification of conserved signature indels (CSIs) and conserved signature proteins (CSPs) that are specific for different lineages. These molecular markers provide novel and more definitive means for demarcation of prokaryotic taxa and for identification of species from these groups. Genome sequences are also enabling determination of phylogenetic relationships among species based upon sequences for multiple proteins. In this work, we have used all of these approaches for studying the phytopathogenic bacteria belonging to the genera Dickeya, Pectobacterium and Brenneria. Members of these genera, which cause numerous diseases in important food crops and ornamental plants, are presently distinguished mainly on the basis of their branching in phylogenetic trees. No biochemical or molecular characteristic is known that is uniquely shared by species from these genera. Hence, detailed studies using the above approaches were carried out on proteins from the genomes of these bacteria to identify molecular markers that are specific for them. In phylogenetic trees based upon concatenated sequences for 23 conserved proteins, members of the genera Dickeya, Pectobacterium and Brenneria formed a strongly supported clade within the other Enterobacteriales. Comparative analysis of protein sequences from the Dickeya, Pectobacterium and Brenneria genomes has identified 10 CSIs and five CSPs that are either uniquely or largely found in all genome-sequenced species from these genera, but not present in any other bacteria in the database. In addition, our analyses have identified 10 CSIs and 17 CSPs that are specifically present in either all or most sequenced Dickeya species/strains, and six CSIs and 19 CSPs that are uniquely found in the sequenced Pectobacterium genomes. Finally, our analysis also identified three CSIs

  1. Colorful Conservation

    Science.gov (United States)

    Skophammer, Karen

    2011-01-01

    Some people only think about conservation on Earth Day. Being in the "art business" however, this author is always conscious of the many products she thinks get wasted when they could be reused, recycled, and restored--especially in a school building and art room. In this article, she describes an art lesson that allows students to paint…

  2. [Conservation Units.

    Science.gov (United States)

    Texas Education Agency, Austin.

    Each of the six instructional units deals with one aspect of conservation: forests, water, rangeland, minerals (petroleum), and soil. The area of the elementary school curriculum with which each correlates is indicated. Lists of general and specific objectives are followed by suggested teaching procedures, including ideas for introducing the…

  3. [Conservation Units.

    Science.gov (United States)

    Texas Education Agency, Austin.

    Instructional units deal with each aspect of conservation: forests, wildlife, rangelands, water, minerals, and soil. The area of the secondary school curriculum with which each is correlated is indicated. Lists of general and specific objectives are followed by suggested teaching procedures, including ideas for introducing the topic, questions to…

  4. Genomics: A Hallmark to Monitor Molecular and Biochemical Processes Leading Toward a Better Perceptive of Seed Aging and ex-situ Conservation.

    Science.gov (United States)

    Ahmed, Zaheer; Shah, Zahid Hussain; Rehman, Hafiz Mamoon; Shahzad, Khurram; Daur, Ihsanullah; Elfeel, Abdalla; Hassan, Mahmood Ul; Elsafori, Ali Khalid; Yang, Seung Hwan; Chung, Gyuhwa

    2017-01-01

    For human food security, the preservation of 7.4 million ex-situ germplasm is a global priority. However, ex-situ-conserved seeds are subject to aging, which reduces their viability and ultimately results in the loss of valuable genetic material over long periods. Recent progress in seed biology and genomics has revealed new opportunities to improve the long-term storage of ex-situ seed germplasm. This review summarizes the recent improvements in seed physiology and genomics, with the intention of developing genomic tools for evaluating seed aging. Several lines of seed biology research have shown promise in retrieving viability signal from various stages of seed germination. We conclude that seed aging is associated with mitochondrial alteration and programmed cell death, DNA and enzyme repair, anti-oxidative genes, telomere length, and epigenetic regulation. Clearly, opportunities exist for observing seed aging for developing genomic tools to increment the traditional germination test for effective conservation of ex-situ germplasm.

  5. Stabilizing Randomly Switched Systems

    CERN Document Server

    Chatterjee, Debasish

    2008-01-01

    This article is concerned with stability analysis and stabilization of randomly switched systems under a class of switching signals. The switching signal is modeled as a jump stochastic (not necessarily Markovian) process independent of the system state; it selects, at each instant of time, the active subsystem from a family of systems. Sufficient conditions for stochastic stability (almost sure, in the mean, and in probability) of the switched system are established when the subsystems do not possess control inputs, and not every subsystem is required to be stable. These conditions are employed to design stabilizing feedback controllers when the subsystems are affine in control. The analysis is carried out with the aid of multiple Lyapunov-like functions, and the analysis results together with universal formulae for feedback stabilization of nonlinear systems constitute our primary tools for control design

  6. Molecular characterization of flavanone 3 beta-hydroxylases. Consensus sequence, comparison with related enzymes and the role of conserved histidine residues.

    Science.gov (United States)

    Britsch, L; Dedio, J; Saedler, H; Forkmann, G

    1993-10-15

    A heterologous cDNA probe from Petunia hybrida was used to isolate flavanone-3 beta-hydroxylase-encoding cDNA clones from carnation (Dianthus caryophyllus), china aster (Callistephus chinensis) and stock (Matthiola incana). The deduced protein sequences together with the known sequences of the enzyme from P. hybrida, barley (Hordeum vulgare) and snapdragon (Antirrhinum majus) enabled the determination of a consensus sequence which revealed an overall 84% similarity (53% identity) of flavanone 3 beta-hydroxylases from the different sources. Alignment with the sequences of other known enzymes of the same class and to related non-heme iron-(II) enzymes demonstrated the strict genetic conservation of 14 amino acids, in particular, of three histidines and an aspartic acid. The conservation of the histidine motifs provides strong support for the possible conservation of structurally similar iron-binding sites in these enzymes. The putative role of histidines as chelators of ferrous ions in the active site of flavanone 3 beta-hydroxylases was corroborated by diethyl-pyrocarbonate modification of the partially purified recombinant Petunia enzyme.

  7. Optical fiber crossbar switch

    Science.gov (United States)

    Kilcoyne, Michael K.; Beccue, Stephen M.; Brar, Berinder; Robinson, G.; Pedrotti, Kenneth D.; Haber, William A.

    1990-07-01

    Advances in high performance computers and signal processing systems have led to parallel system architectures. The main limitation in achieving the performance expected of these parallel systems has been the realization of an efficient means to interconnect many processors into a effective parallel system. Electronic interconnections have proved cumbersome, costly and ineffective. The Optical Fiber Crossbar Switch (OFCS) is a compact low power, multi-gigahertz bandwidth multi-channel switch which can be used in large scale computer and telecommunication applications. The switch operates in the optical domain using GaAs semiconductor lasers to transmit wideband multiple channel optical data over fiber optic cables. Recently, a 32 X 32 crossbar switching system was completed and demonstrated. Error free performance was obtained at a data bandwidth of 410 MBPS, using a silicon switch IC. The switch can be completely reconfigured in less than 50 nanoseconds under computer control. The fully populated OFCS has the capability to handle 12.8 gigabits per second (GBPS) of data while switching this data over 32 channels without the loss of a single bit during switching. GaAs IC technology has now progressed to the point that 16 X 16 GaAs based crossbar switch Ics are available which have increased the data bandwidth capability to 2.4 GBPS. The present optical interfaces are integrated GaAs transmitter drivers, GaAs lasers, and integrated GaAs optical receivers with data bandwidths exceeding 2.4 GBPS. A system using all Ill-V switching and optoelectronic components is presently under development for both NASA and DoD programs. The overall system is designed to operate at 1.3 GBPS. It is expected that these systems will find wide application in high capacity computing systems based on parallel microprocessor architecture which require high data bandwidth communication between processors. The OFCS will also have application in commercial optical telecommunication systems

  8. High Power Switching Transistor

    Science.gov (United States)

    Hower, P. L.; Kao, Y. C.; Carnahan, D. C.

    1983-01-01

    Improved switching transistors handle 400-A peak currents and up to 1,200 V. Using large diameter silicon wafers with twice effective area as D60T, form basis for D7 family of power switching transistors. Package includes npn wafer, emitter preform, and base-contact insert. Applications are: 25to 50-kilowatt high-frequency dc/dc inverters, VSCF converters, and motor controllers for electrical vehicles.

  9. Photonics in switching

    CERN Document Server

    Midwinter, John E; Kelley, Paul

    1993-01-01

    Photonics in Switching provides a broad, balanced overview of the use of optics or photonics in switching, from materials and devices to system architecture. The chapters, each written by an expert in the field, survey the key technologies, setting them in context and highlighting their benefits and possible applications. This book is a valuable resource for those working in the communications industry, either at the professional or student level, who do not have extensive background knowledge or the underlying physics of the technology.

  10. 微生物分子生态学技术在文物保护中应用的进展%Application of microbial molecular ecology in conservation of cultural heritage

    Institute of Scientific and Technical Information of China (English)

    王亚丽

    2012-01-01

    微生物分子生态学技术近年来在文物保护研究中得到了广泛的应用,已经成为控制文物被微生物侵害的一个不可或缺的工具。本研究较系统地总结了国内外利用微生物分子生态学技术进行文物保护研究的进展,为更有效防治微生物危害侵蚀文物,进而长久的保存文物提供理论支持。%In recent years, microbial molecular ecology has been widely applied in the field of conservation. This article reviews the domestic and international application of microbial ecology technology for conservation of cultural heritage objects, so as to effectively prevent microbiological damage to them. This review provides theoretical foun- dations for long - term conservation of cultural heritage objects.

  11. Low inductance gas switching.

    Energy Technology Data Exchange (ETDEWEB)

    Chavez, Ray; Harjes, Henry Charles III; Wallace, Zachariah; Elizondo, Juan E.

    2007-10-01

    The laser trigger switch (LTS) is a key component in ZR-type pulsed power systems. In ZR, the pulse rise time through the LTS is > 200 ns and additional stages of pulse compression are required to achieve the desired <100 ns rise time. The inductance of the LTS ({approx}500nH) in large part determines the energy transfer time through the switch and there is much to be gained in improving system performance and reducing system costs by reducing this inductance. The current path through the cascade section of the ZR LTS is at a diameter of {approx} 6-inches which is certainly not optimal from an inductance point of view. The LTS connects components of much greater diameter (typically 4-5 feet). In this LDRD the viability of switch concepts in which the diameter of cascade section is greatly increased have been investigated. The key technical question to be answered was, will the desired multi-channel behavior be maintained in a cascade section of larger diameter. This LDRD proceeded in 2 distinct phases. The original plan for the LDRD was to develop a promising switch concept and then design, build, and test a moderate scale switch which would demonstrate the key features of the concept. In phase I, a switch concept which meet all electrical design criteria and had a calculated inductance of 150 nH was developed. A 1.5 MV test switch was designed and fabrication was initiated. The LDRD was then redirected due to budgetary concerns. The fabrication of the switch was halted and the focus of the LDRD was shifted to small scale experiments designed to answer the key technical question concerning multi-channel behavior. In phase II, the Multi-channel switch test bed (MCST) was designed and constructed. The purpose of MCST was to provide a versatile, fast turn around facility for the study the multi-channel electrical breakdown behavior of a ZR type cascade switch gap in a parameter space near that of a ZR LTS. Parameter scans on source impedance, gap tilt, gap spacing and

  12. Heron conservation

    Science.gov (United States)

    Kushlan, J.A.; Hafner, H.

    2000-01-01

    Herons are large, popular and, in many cases, spectacular birds found in wetlands world-wide, both tropical and temperate, natural and man-made. Some populations are very small and localized, some have decreased, some have expanded their ranges, and a few are pests of human activities. In the fifteen years since the publication of the latest monographic treatment of the family, The Herons Handbook, there has been a tremendous increase in our knowledge of heron status and conservation requirements, set against a backdrop of increasing concern about the future of the world?s wetland habitats. This book provides a comprehensive update following two distinct threads. The status and conservation needs of herons are first presented on a regional basis, in a series of chapters set at a continental or subcontinental scale. Over 200 biologists and heron conservationists have contributed to the data summarized here, and the very latest census and survey results provide the most up-to-date and detailed picture of heron populations currently available. Chapters discussing several critical issues in heron conservation follow, tending to focus on the international nature of the problems.

  13. Energy losses in switches

    Energy Technology Data Exchange (ETDEWEB)

    Martin, T.H.; Seamen, J.F.; Jobe, D.O.

    1993-07-01

    The authors experiments show energy losses between 2 and 10 times that of the resistive time predictions. The experiments used hydrogen, helium, air, nitrogen, SF{sub 6} polyethylene, and water for the switching dielectric. Previously underestimated switch losses have caused over predicting the accelerator outputs. Accurate estimation of these losses is now necessary for new high-efficiency pulsed power devices where the switching losses constitute the major portion of the total energy loss. They found that the switch energy losses scale as (V{sub peak}I{sub peak}){sup 1.1846}. When using this scaling, the energy losses in any of the tested dielectrics are almost the same. This relationship is valid for several orders of magnitude and suggested a theoretical basis for these results. Currents up to .65 MA, with voltages to 3 MV were applied to various gaps during these experiments. The authors data and the developed theory indicates that the switch power loss continues for a much longer time than the resistive time, with peak power loss generally occurring at peak current in a ranging discharge instead of the early current time. All of the experiments were circuit code modeled after developing a new switch loss version based on the theory. The circuit code predicts switch energy loss and peak currents as a function of time. During analysis of the data they noticed slight constant offsets between the theory and data that depended on the dielectric. They modified the plasma conductivity for each tested dielectric to lessen this offset.

  14. Stabilization of a class of discrete-time switched systems via observer-based output feedback

    Institute of Scientific and Technical Information of China (English)

    Jiao LI; Yuzhong LIU

    2007-01-01

    In this paper, observer-based static output feedback control problem for discrete-time uncertain switched systems is investigated under an arbitrary switching rule. The main method used in this note is combining switched. Lyapunov function (SLF) method with Finsler's Lemma. Based on linear matrix inequality (LMI) a less conservative stability condition is established and this condition allows extra degree of freedom for stability analysis. Finally, a simulation example is given to illustrate the efficiency of the result.

  15. Development of microsatellite markers as a molecular tool for conservation studies of the Mediterranean reef builder coral Cladocora caespitosa (Anthozoa, Scleractinia).

    Science.gov (United States)

    Casado-Amezúa, Pilar; García-Jiménez, Ricardo; Kersting, Diego K; Templado, José; Coffroth, Mary Alice; Merino, Paula; Acevedo, Iván; Machordom, Annie

    2011-01-01

    Cladocora caespitosa is a reef-building zooxanthellate scleractinian coral in the Mediterranean Sea. Mortality events have recurrently affected this species during the last decade. Thus, knowledge of its genetic structure, population diversity, and connectivity is needed to accomplish suitable conservation plans. In order to obtain a better understanding of the population genetics of this species, 13 highly variable microsatellites markers were developed from a naturally bleached colony. The developed primers failed to amplify zooxanthella DNA, isolated from C. caespitosa, verifying that these markers were of the coral and not algal symbiont origin. The degree of polymorphism of these loci was tested on tissue samples from 28 colonies. The allele number for each loci ranged from 2 to 13 (mean N(a) = 5.4), with an average observed heterozygosity of 0.42 (H(e) = 0.43) and all loci were in Hardy-Weinberg equilibrium. These new markers should be useful in future conservation genetic studies and will help to improve the resolution of the individual identification within this coral species. Primers were also tested in Oculina patagonica, with successful amplifications of several loci.

  16. Atomic Scale Plasmonic Switch.

    Science.gov (United States)

    Emboras, Alexandros; Niegemann, Jens; Ma, Ping; Haffner, Christian; Pedersen, Andreas; Luisier, Mathieu; Hafner, Christian; Schimmel, Thomas; Leuthold, Juerg

    2016-01-13

    The atom sets an ultimate scaling limit to Moore's law in the electronics industry. While electronics research already explores atomic scales devices, photonics research still deals with devices at the micrometer scale. Here we demonstrate that photonic scaling, similar to electronics, is only limited by the atom. More precisely, we introduce an electrically controlled plasmonic switch operating at the atomic scale. The switch allows for fast and reproducible switching by means of the relocation of an individual or, at most, a few atoms in a plasmonic cavity. Depending on the location of the atom either of two distinct plasmonic cavity resonance states are supported. Experimental results show reversible digital optical switching with an extinction ratio of 9.2 dB and operation at room temperature up to MHz with femtojoule (fJ) power consumption for a single switch operation. This demonstration of an integrated quantum device allowing to control photons at the atomic level opens intriguing perspectives for a fully integrated and highly scalable chip platform, a platform where optics, electronics, and memory may be controlled at the single-atom level.

  17. Deliberate Switching of Single Photochromic Triads

    Science.gov (United States)

    Maier, Johannes; Pärs, Martti; Weller, Tina; Thelakkat, Mukundan; Köhler, Jürgen

    2017-01-01

    Photochromic molecules can be reversibly converted between two bistable conformations by light, and are considered as promising building blocks in novel macromolecular structures for sensing and imaging techniques. We have studied individual molecular triads consisting of two strong fluorophores (perylene bisimide) that are covalently linked via a photochromic unit (dithienylcyclopentene) and distinguished between deliberate switching and spontaneous blinking. It was verified that the probability for observing deliberate light-induced switching of a single triad (rather than stochastic blinking) amounts to 0.8 ± 0.1. In a few exceptional cases this probability can exceed 0.95. These numbers are sufficiently large for application in sensitive biosensing, and super-resolution imaging. This opens the possibility to develop devices that can be controlled by an external optical stimulus on a truly molecular length scale.

  18. Orientation of KRb molecules in a switched electrostatic field

    Institute of Scientific and Technical Information of China (English)

    Huang Yun-Xia; Xu Shu-Wu; Yang Xiao-Hua

    2013-01-01

    We theoretically investigate the orientation of the cold KRb molecules induced in a switched electrostatic field by numerically solving the full time-dependent Schr(o)dinger equation.The results show that the periodic field-free molecular orientation can be realized for the KRb molecules by rapidly switching off the electrostatic field.Meanwhile,by varying the switching times of the electrostatic field,the adiabatic and nonadiabatic interactions of the molecules with the applied field can be realized.Moreover,the influences of the electrostatic field strength and the rotational temperature to the degree of the molecular orientation are studied.The investigations show that increasing the electrostatic field will increase the degree of the molecular orientation,both in the constant-field regime and in the field-free regime,while the increasing of the rotational temperature of the cold molecules will greatly decrease the degree of the molecular orientation.

  19. On stability of switched linear systems with perturbed switching paths

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    This paper addresses the stability issue of switched linear systems with perturbed switching paths. First,by introducing thenotions of child-path and parent-path, we are able to define the distance between two switching paths by means of their switching matrices chains. Next, we present the nice properties of the defined distance. Then, a stability criterion is presented for a class of switched linear systems with perturbed switching paths. Finally, an illustrative example is presented to verify the effectiveness of the approach.

  20. Energy reversible switching from amorphous metal based nanoelectromechanical switch

    KAUST Repository

    Mayet, Abdulilah M.

    2013-08-01

    We report observation of energy reversible switching from amorphous metal based nanoelectromechanical (NEM) switch. For ultra-low power electronics, NEM switches can be used as a complementary switching element in many nanoelectronic system applications. Its inherent zero power consumption because of mechanical detachment is an attractive feature. However, its operating voltage needs to be in the realm of 1 volt or lower. Appropriate design and lower Young\\'s modulus can contribute achieving lower operating voltage. Therefore, we have developed amorphous metal with low Young\\'s modulus and in this paper reporting the energy reversible switching from a laterally actuated double electrode NEM switch. © 2013 IEEE.

  1. Chemical Reaction Rates from Ring Polymer Molecular Dynamics: Zero Point Energy Conservation in Mu + H2 → MuH + H.

    Science.gov (United States)

    Pérez de Tudela, Ricardo; Aoiz, F J; Suleimanov, Yury V; Manolopoulos, David E

    2012-02-16

    A fundamental issue in the field of reaction dynamics is the inclusion of the quantum mechanical (QM) effects such as zero point energy (ZPE) and tunneling in molecular dynamics simulations, and in particular in the calculation of chemical reaction rates. In this work we study the chemical reaction between a muonium atom and a hydrogen molecule. The recently developed ring polymer molecular dynamics (RPMD) technique is used, and the results are compared with those of other methods. For this reaction, the thermal rate coefficients calculated with RPMD are found to be in excellent agreement with the results of an accurate QM calculation. The very minor discrepancies are within the convergence error even at very low temperatures. This exceptionally good agreement can be attributed to the dominant role of ZPE in the reaction, which is accounted for extremely well by RPMD. Tunneling only plays a minor role in the reaction.

  2. Microfabricated triggered vacuum switch

    Science.gov (United States)

    Roesler, Alexander W.; Schare, Joshua M.; Bunch, Kyle

    2010-05-11

    A microfabricated vacuum switch is disclosed which includes a substrate upon which an anode, cathode and trigger electrode are located. A cover is sealed over the substrate under vacuum to complete the vacuum switch. In some embodiments of the present invention, a metal cover can be used in place of the trigger electrode on the substrate. Materials used for the vacuum switch are compatible with high vacuum, relatively high temperature processing. These materials include molybdenum, niobium, copper, tungsten, aluminum and alloys thereof for the anode and cathode. Carbon in the form of graphitic carbon, a diamond-like material, or carbon nanotubes can be used in the trigger electrode. Channels can be optionally formed in the substrate to mitigate against surface breakdown.

  3. DNA replication: stalling a fork for imprinting and switching

    DEFF Research Database (Denmark)

    Egel, Richard

    2004-01-01

    Mating-type switching in fission yeast has long been known to be directed by a DNA 'imprint'. This imprint has now been firmly characterized as a protected site-specific and strand-specific nick. New work also links the widely conserved Swi1-Swi3 complex to the protection of stalled replication...

  4. Molecular footprinting of skeletal tissues in the catshark Scyliorhinus canicula and the clawed frog Xenopus tropicalis identifies conserved and derived features of vertebrate calcification

    Directory of Open Access Journals (Sweden)

    Sebastien eEnault

    2015-09-01

    Full Text Available Understanding the evolutionary emergence and subsequent diversification of the vertebrate skeleton requires a comprehensive view of the diverse skeletal cell types found in distinct developmental contexts, tissues and species. To date, our knowledge of the molecular nature of the shark calcified extracellular matrix, and its relationships with osteichthyan skeletal tissues, remain scarce. Here, based on specific combinations of expression patterns of the Col1a1, Col1a2 and Col2a1 fibrillar collagen genes, we compare the molecular footprint of endoskeletal elements from the chondrichthyan Scyliorhinus canicula and the tetrapod Xenopus tropicalis. We find that, depending on the anatomical location, Scyliorhinus skeletal calcification is associated to cell types expressing different subsets of fibrillar collagen genes, such as high levels of Col1a1 and Col1a2 in the neural arches, high levels of Col2a1 in the tesserae, or associated to a drastic Col2a1 downregulation in the centrum. We detect low Col2a1 levels in Xenopus osteoblasts, thereby revealing that the osteoblastic expression of this gene was significantly reduced in the tetrapod lineage. Finally, we uncover a striking parallel, from a molecular and histological perspective, between the vertebral cartilage calcification of both species and discuss the evolutionary origin of endochondral ossification.

  5. Cooperative Switching in Nanofibers of Azobenzene Oligomers

    Science.gov (United States)

    Weber, Christopher; Liebig, Tobias; Gensler, Manuel; Zykov, Anton; Pithan, Linus; Rabe, Jürgen P.; Hecht, Stefan; Bléger, David; Kowarik, Stefan

    2016-05-01

    Next-generation molecular devices and machines demand the integration of molecular switches into hierarchical assemblies to amplify the response of the system from the molecular level to the meso- or macro-scale. Here, we demonstrate that multi-azobenzene oligomers can assemble to form robust supramolecular nanofibers in which they can be switched repeatedly between the E- and Z-configuration. While in isolated oligomers the azobenzene units undergo reversible photoisomerization independently, in the nanofibers they are coupled via intermolecular interactions and switch cooperatively as evidenced by unusual thermal and kinetic behavior. We find that the photoisomerization rate from the Z-isomer to the E-isomer depends on the fraction of Z-azobenzene in the nanofibers, and is increased by more than a factor of 4 in Z-rich fibers when compared to E-rich fibers. This demonstrates the great potential of coupling individual photochromic units for increasing their quantum efficiency in the solid state with potential relevance for actuation and sensing.

  6. Beyond the switch

    DEFF Research Database (Denmark)

    Aliakseyeu, Dzmitry; Meerbeek, Bernt; Mason, Jon

    2014-01-01

    and established lighting network, and with the advent of the LED, new types of lighting output are now possible. However, the current approach for controlling such systems is to simply replace the light switch with a somewhat more sophisticated smartphone-based remote control. The focus of this workshop...... is to explore new ways of interacting with light where lighting can not only be switched on or off, but is an intelligent system embedded in the environment capable of creating a variety of effects. The connectivity between multiple systems and other ecosystems, for example when transitioning from your home...

  7. Optical Packet Switching Demostrator

    DEFF Research Database (Denmark)

    Mortensen, Brian Bach; Berger, Michael Stübert

    2002-01-01

    In the IST project DAVID (data and voice integration over DWDM) work is carried out defining possible architectures of future optical packet switched networks. The feasibility of the architecture is to be verified in a demonstration set-up. This article describes the demonstrator set-up and the m......In the IST project DAVID (data and voice integration over DWDM) work is carried out defining possible architectures of future optical packet switched networks. The feasibility of the architecture is to be verified in a demonstration set-up. This article describes the demonstrator set...

  8. A Switched Capacitor Harmonic Compensation Part for Switching Supplies

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    A new approach based on switched capacitor network to harmonic compensation for switching supplies is presented in the paper,The basic principle is discussed.SPICE simulation is applied to analyze the behaviour of the switched capacitor harmonic compensation part.

  9. The Octopus switch

    NARCIS (Netherlands)

    Havinga, Paul Johannes Mattheus

    2000-01-01

    This chapter1 discusses the interconnection architecture of the Mobile Digital Companion. The approach to build a low-power handheld multimedia computer presented here is to have autonomous, reconfigurable modules such as network, video and audio devices, interconnected by a switch rather than by a

  10. DIGITAL TELEPHONE SWITCH: SOFTWARE

    Directory of Open Access Journals (Sweden)

    J. G. Viveros Talavera

    2003-07-01

    Full Text Available This paper describes the design of the program of control for a Digital Phone Switch (PBAX with a maximumcapacity of one hundred and twenty-eight lines (extensions and trunks. The control program was designedusing object-oriented programming and concurrent programming techniques.

  11. Kiowa Creek Switching Station

    Energy Technology Data Exchange (ETDEWEB)

    1990-03-01

    The Western Area Power Administration (Western) proposes to construct, operate, and maintain a new Kiowa Creek Switching Station near Orchard in Morgan County, Colorado. Kiowa Creek Switching Station would consist of a fenced area of approximately 300 by 300 feet and contain various electrical equipment typical for a switching station. As part of this new construction, approximately one mile of an existing 115-kilovolt (kV) transmission line will be removed and replaced with a double circuit overhead line. The project will also include a short (one-third mile) realignment of an existing line to permit connection with the new switching station. In accordance with the Council on Environmental Quality (CEQ) regulations for implementing the procedural provisions of the National Environmental Policy Act of 1969 (NEPA), 40 CFR Parts 1500--1508, the Department of Energy (DOE) has determined that an environmental impact statement (EIS) is not required for the proposed project. This determination is based on the information contained in this environmental assessment (EA) prepared by Western. The EA identifies and evaluates the environmental and socioeconomic effects of the proposed action, and concludes that the advance impacts on the human environment resulting from the proposed project would not be significant. 8 refs., 3 figs., 1 tab.

  12. Photonic MEMS switch applications

    Science.gov (United States)

    Husain, Anis

    2001-07-01

    As carriers and service providers continue their quest for profitable network solutions, they have shifted their focus from raw bandwidth to rapid provisioning, delivery and management of revenue generating services. Inherently transparent to data rate the transmission wavelength and data format, MEMS add scalability, reliability, low power and compact size providing flexible solutions to the management and/or fiber channels in long haul, metro, and access networks. MEMS based photonic switches have gone from the lab to commercial availability and are now currently in carrier trials and volume production. 2D MEMS switches offer low up-front deployment costs while remaining scalable to large arrays. They allow for transparent, native protocol transmission. 2D switches enable rapid service turn-up and management for many existing and emerging revenue rich services such as storage connectivity, optical Ethernet, wavelength leasing and optical VPN. As the network services evolve, the larger 3D MEMS switches, which provide greater scalability and flexibility, will become economically viable to serve the ever-increasing needs.

  13. Safe LPV Controller Switching

    DEFF Research Database (Denmark)

    Trangbæk, K

    2010-01-01

    Before switching to a new controller it is crucial to assure that the new closed loop will be stable. In this paper it is demonstrated how stability can be checked with limited measurement data available from the current closed loop. The paper extends an existing method to linear parameter varying...

  14. Switching Between Multivariable Controllers

    DEFF Research Database (Denmark)

    Niemann, Hans Henrik; Stoustrup, Jakob; Abrahamsen, Rune

    2004-01-01

    it is possible to smoothly switch between multivariable controllers with guaranteed closed-loop stability. This includes also the case where one or more controllers are unstable. The concept for smooth online changes of multivariable controllers based on the YJBK architecture can also handle the start up...

  15. Kiowa Creek Switching Station

    Energy Technology Data Exchange (ETDEWEB)

    1990-03-01

    The Western Area Power Administration (Western) proposes to construct, operate, and maintain a new Kiowa Creek Switching Station near Orchard in Morgan County, Colorado. Kiowa Creek Switching Station would consist of a fenced area of approximately 300 by 300 feet and contain various electrical equipment typical for a switching station. As part of this new construction, approximately one mile of an existing 115-kilovolt (kV) transmission line will be removed and replaced with a double circuit overhead line. The project will also include a short (one-third mile) realignment of an existing line to permit connection with the new switching station. In accordance with the Council on Environmental Quality (CEQ) regulations for implementing the procedural provisions of the National Environmental Policy Act of 1969 (NEPA), 40 CFR Parts 1500--1508, the Department of Energy (DOE) has determined that an environmental impact statement (EIS) is not required for the proposed project. This determination is based on the information contained in this environmental assessment (EA) prepared by Western. The EA identifies and evaluates the environmental and socioeconomic effects of the proposed action, and concludes that the advance impacts on the human environment resulting from the proposed project would not be significant. 8 refs., 3 figs., 1 tab.

  16. Closing photoconductive semiconductor switches

    Energy Technology Data Exchange (ETDEWEB)

    Loubriel, G.M.; Zutavern, F.J.; Hjalmarson, H.P.; O' Malley, M.W.

    1989-01-01

    One of the most important limitations of Photoconductive Semiconductor Switches (PCSS) for pulsed power applications is the high laser powers required to activate the switches. In this paper, we discuss recent developments on two different aspects of GaAs PCSS that result in reductions in laser power by a factor of nearly 1000. The advantages of using GaAs over Si are many. First of all, the resistivity of GaAs can be orders of magnitude higher than that of the highest resistivity Si material, thus allowing GaAs switches to withstand dc voltages without thermal runaway. Secondly, GaAs has a higher carrier mobility than Si and, thus, is more efficient (per carrier). Finally, GaAs switches can have naturally fast (ns) opening times at room temperature and low fields, microsecond opening times at liquid nitrogen temperature of 77 K, or, on demand, closing and opening at high fields and room temperature by a mechanism called lock-on (see Ref. 1). By contrast, Si switches typically opening times of milliseconds. The amount of laser light required to trigger GaAs for lock-on, or at 77 K, is about three orders of magnitude lower than at room temperature. In this paper we describe the study of lock-on in GaAs and InP, as well as switching of GaAs at 77 K. We shall show that when GaAs is switched at 77 K, the carrier lifetime is about three orders of magnitude longer than it is at room temperature. We shall explain the change in lifetime in terms of the change in electron capture cross section of the deep levels in GaAs (these are defect or impurity levels in the band gap). In the second section, we describe the lock-on effect, now seen in GaAs and InP, and at fields as high as 70 kV/cm. We show how lock-on can be tailored by changing the GaAs temperature or by neutron bombardment. In the third section, we discuss possible lock-on mechanisms. 5 refs., 5 figs.

  17. Heat-transfer thermal switch

    Science.gov (United States)

    Friedell, M. V.; Anderson, A. J.

    1974-01-01

    Thermal switch maintains temperature of planetary lander, within definite range, by transferring heat. Switch produces relatively large stroke and force, uses minimum electrical power, is lightweight, is vapor pressure actuated, and withstands sterilization temperatures without damage.

  18. Control synthesis of switched systems

    CERN Document Server

    Zhao, Xudong; Niu, Ben; Wu, Tingting

    2017-01-01

    This book offers its readers a detailed overview of the synthesis of switched systems, with a focus on switching stabilization and intelligent control. The problems investigated are not only previously unsolved theoretically but also of practical importance in many applications: voltage conversion, naval piloting and navigation and robotics, for example. The book considers general switched-system models and provides more efficient design methods to bring together theory and application more closely than was possible using classical methods. It also discusses several different classes of switched systems. For general switched linear systems and switched nonlinear systems comprising unstable subsystems, it introduces novel ideas such as invariant subspace theory and the time-scheduled Lyapunov function method of designing switching signals to stabilize the underlying systems. For some typical switched nonlinear systems affected by various complex dynamics, the book proposes novel design approaches based on inte...

  19. Illuminated push-button switch

    Science.gov (United States)

    Iwagiri, T.

    1983-01-01

    An illuminated push-button switch is described. It is characterized by the fact that is consists of a switch group, an operator button opening and closing the switch group, and a light-emitting element which illuminates the face of the operator button.

  20. Abacus switch: a new scalable multicast ATM switch

    Science.gov (United States)

    Chao, H. Jonathan; Park, Jin-Soo; Choe, Byeong-Seog

    1995-10-01

    This paper describes a new architecture for a scalable multicast ATM switch from a few tens to thousands of input ports. The switch, called Abacus switch, has a nonblocking memoryless switch fabric followed by small switch modules at the output ports; the switch has input and output buffers. Cell replication, cell routing, output contention resolution, and cell addressing are all performed distributedly in the Abacus switch so that it can be scaled up to thousnads input and output ports. A novel algorithm has been proposed to resolve output port contention while achieving input and output ports. A novel algorithm has been proposed to reolve output port contention while achieving input buffers sharing, fairness among the input ports, and multicast call splitting. The channel grouping concept is also adopted in the switch to reduce the hardware complexity and improve the switch's throughput. The Abacus switch has a regular structure and thus has the advantages of: 1) easy expansion, 2) relaxed synchronization for data and clock signals, and 3) building the switch fabric using existing CMOS technology.

  1. Mapping Flexibility and the Assembly Switch of Cell Division Protein FtsZ by Computational and Mutational Approaches*♦

    Science.gov (United States)

    Martín-Galiano, Antonio J.; Buey, Rubén M.; Cabezas, Marta; Andreu, José M.

    2010-01-01

    The molecular switch for nucleotide-regulated assembly and disassembly of the main prokaryotic cell division protein FtsZ is unknown despite the numerous crystal structures that are available. We have characterized the functional motions in FtsZ with a computational consensus of essential dynamics, structural comparisons, sequence conservation, and networks of co-evolving residues. Employing this information, we have constructed 17 mutants, which alter the FtsZ functional cycle at different stages, to modify FtsZ flexibility. The mutant phenotypes ranged from benign to total inactivation and included increased GTPase, reduced assembly, and stabilized assembly. Six mutations clustering at the long cleft between the C-terminal β-sheet and core helix H7 deviated FtsZ assembly into curved filaments with inhibited GTPase, which still polymerize cooperatively. These mutations may perturb the predicted closure of the C-terminal domain onto H7 required for switching between curved and straight association modes and for GTPase activation. By mapping the FtsZ assembly switch, this work also gives insight into FtsZ druggability because the curved mutations delineate the putative binding site of the promising antibacterial FtsZ inhibitor PC190723. PMID:20472561

  2. Immunoglobulin class-switch recombination deficiencies.

    Science.gov (United States)

    Durandy, Anne; Kracker, Sven

    2012-07-30

    Immunoglobulin class-switch recombination deficiencies (Ig-CSR-Ds) are rare primary immunodeficiencies characterized by defective switched isotype (IgG/IgA/IgE) production. Depending on the molecular defect in question, the Ig-CSR-D may be combined with an impairment in somatic hypermutation (SHM). Some of the mechanisms underlying Ig-CSR and SHM have been described by studying natural mutants in humans. This approach has revealed that T cell-B cell interaction (resulting in CD40-mediated signaling), intrinsic B-cell mechanisms (activation-induced cytidine deaminase-induced DNA damage), and complex DNA repair machineries (including uracil-N-glycosylase and mismatch repair pathways) are all involved in class-switch recombination and SHM. However, several of the mechanisms required for full antibody maturation have yet to be defined. Elucidation of the molecular defects underlying the diverse set of Ig-CSR-Ds is essential for understanding Ig diversification and has prompted better definition of the clinical spectrum of diseases and the development of increasingly accurate diagnostic and therapeutic approaches.

  3. Practical switching power supply design

    CERN Document Server

    Brown, Martin C

    1990-01-01

    Take the ""black magic"" out of switching power supplies with Practical Switching Power Supply Design! This is a comprehensive ""hands-on"" guide to the theory behind, and design of, PWM and resonant switching supplies. You'll find information on switching supply operation and selecting an appropriate topology for your application. There's extensive coverage of buck, boost, flyback, push-pull, half bridge, and full bridge regulator circuits. Special attention is given to semiconductors used in switching supplies. RFI/EMI reduction, grounding, testing, and safety standards are also deta

  4. Laser conservation paleontology

    Science.gov (United States)

    Asmus, John F.

    2001-10-01

    Just as lasers have found countless applications in science, industry, medicine, and entertainment, an array of real and potential uses for lasers in art-conservation analytes and practice have been investigated over the past thirty years. These include holographic recording, holographic recording, holographic nondestructive testing, laser-induced ultrasonic imaging, laser-scattering surface characterization, atomic and molecular analyses, photoacoustic spectroscopy, surface modification, as well as surface divestment and cleaning. The initial endeavors in exploring and assessing the utility of these tools for art conservation are recounted for investigations involving ruby, glass, ion, YAG, carbon dioxide, dye, and excimer lasers as well as high-intensity nonlaser light generators such as xenon flashlamps and argon pinchlamps. Initially, laser divestment/cleaning was, by general consensus, the least plausible laser application in art conservation. In the past ten years it has emerged to dominate all the other applications noted above. Today, at least a dozen firms supply user-friendly laser systems optimized for a range of art-conservation divestment applications. The first-generation laser-cleaning tools are essentially a laser, a beam-delivery device, and a debris- collection accessory. Advanced developmental work has turned in large measure to ancillary subsystems for more sophisticated process control. Of particular importance are acoustic, optical, spectral, EMP, and electronic-vision process control. Beam direction may be via manual, translational-scanner, or robotic beam positioning implemented by means of fiber optics, minors, or prisms and computer control. Substrate thermal alteration and debris redeposition may be minimized or avoided through the incorporation of a gas jet, fluid or fluid jet, or dry-ice blast.

  5. Application of multiplex PCR approaches for shark molecular identification: feasibility and applications for fisheries management and conservation in the Eastern Tropical Pacific.

    Science.gov (United States)

    Caballero, S; Cardeñosa, D; Soler, G; Hyde, J

    2012-03-01

    Here we describe the application of new and existing multiplex PCR methodologies for shark species molecular identification. Four multiplex systems (group ID, thresher sharks, hammerhead sharks and miscellaneous shark) were employed with primers previously described and some designed in this study, which allow for species identification after running PCR products through an agarose gel. This system was implemented for samples (bodies and fins) collected from unidentified sharks landed in the port of Buenaventura and from confiscated tissues obtained from illegal fishing around the Malpelo Island Marine Protected Area, Pacific Coast of Colombia. This method has allowed reliable identification, to date, of 407 samples to the genus and/or species levels, most of them (380) identified as the pelagic thresher shark (Alopias pelagicus). Another seven samples were identified as scalloped hammerhead sharks (Sphyrna lewini). This is an easy-to-implement and reliable identification method that could even be used locally to monitor shark captures in the main fishing ports of developed and developing countries.

  6. Switched-Observer-Based Adaptive Neural Control of MIMO Switched Nonlinear Systems With Unknown Control Gains.

    Science.gov (United States)

    Long, Lijun; Zhao, Jun

    2016-05-02

    In this paper, the problem of adaptive neural output-feedback control is addressed for a class of multi-input multioutput (MIMO) switched uncertain nonlinear systems with unknown control gains. Neural networks (NNs) are used to approximate unknown nonlinear functions. In order to avoid the conservativeness caused by adoption of a common observer for all subsystems, an MIMO NN switched observer is designed to estimate unmeasurable states. A new switched observer-based adaptive neural control technique for the problem studied is then provided by exploiting the classical average dwell time (ADT) method and the backstepping method and the Nussbaum gain technique. It effectively handles the obstacle about the coexistence of multiple Nussbaum-type function terms, and improves the classical ADT method, since the exponential decline property of Lyapunov functions for individual subsystems is no longer satisfied. It is shown that the technique proposed is able to guarantee semiglobal uniformly ultimately boundedness of all the signals in the closed-loop system under a class of switching signals with ADT, and the tracking errors converge to a small neighborhood of the origin. The effectiveness of the approach proposed is illustrated by its application to a two inverted pendulum system.

  7. Python Switch Statement

    Directory of Open Access Journals (Sweden)

    2008-06-01

    Full Text Available The Python programming language does not have a built in switch/case control structure as found in many other high level programming languages. It is thought by some that this is a deficiency in the language, and the control structure should be added. This paper demonstrates that not only is the control structure not needed, but that the methods available in Python are more expressive than built in case statements in other high level languages.

  8. "Platform switching": Serendipity

    Directory of Open Access Journals (Sweden)

    N Kalavathy

    2014-01-01

    Full Text Available Implant dentistry is the latest developing field in terms of clinical techniques, research, material science and oral rehabilitation. Extensive work is being done to improve the designing of implants in order to achieve better esthetics and function. The main drawback with respect to implant restoration is achieving good osseointegration along with satisfactory stress distribution, which in turn will improve the prognosis of implant prosthesis by reducing the crestal bone loss. Many concepts have been developed with reference to surface coating of implants, surgical techniques for implant placement, immediate and delayed loading, platform switching concept, etc. This article has made an attempt to review the concept of platform switching was in fact revealed accidentally due to the nonavailability of the abutment appropriate to the size of the implant placed. A few aspect of platform switching, an upcoming idea to reduce crestal bone loss have been covered. The various methods used for locating and preparing the data were done through textbooks, Google search and related articles.

  9. "Platform switching": serendipity.

    Science.gov (United States)

    Kalavathy, N; Sridevi, J; Gehlot, Roshni; Kumar, Santosh

    2014-01-01

    Implant dentistry is the latest developing field in terms of clinical techniques, research, material science and oral rehabilitation. Extensive work is being done to improve the designing of implants in order to achieve better esthetics and function. The main drawback with respect to implant restoration is achieving good osseointegration along with satisfactory stress distribution, which in turn will improve the prognosis of implant prosthesis by reducing the crestal bone loss. Many concepts have been developed with reference to surface coating of implants, surgical techniques for implant placement, immediate and delayed loading, platform switching concept, etc. This article has made an attempt to review the concept of platform switching was in fact revealed accidentally due to the nonavailability of the abutment appropriate to the size of the implant placed. A few aspect of platform switching, an upcoming idea to reduce crestal bone loss have been covered. The various methods used for locating and preparing the data were done through textbooks, Google search and related articles.

  10. Mutational Studies on Resurrected Ancestral Proteins Reveal Conservation of Site-Specific Amino Acid Preferences throughout Evolutionary History

    Science.gov (United States)

    Risso, Valeria A.; Manssour-Triedo, Fadia; Delgado-Delgado, Asunción; Arco, Rocio; Barroso-delJesus, Alicia; Ingles-Prieto, Alvaro; Godoy-Ruiz, Raquel; Gavira, Jose A.; Gaucher, Eric A.; Ibarra-Molero, Beatriz; Sanchez-Ruiz, Jose M.

    2015-01-01

    Local protein interactions (“molecular context” effects) dictate amino acid replacements and can be described in terms of site-specific, energetic preferences for any different amino acid. It has been recently debated whether these preferences remain approximately constant during evolution or whether, due to coevolution of sites, they change strongly. Such research highlights an unresolved and fundamental issue with far-reaching implications for phylogenetic analysis and molecular evolution modeling. Here, we take advantage of the recent availability of phenotypically supported laboratory resurrections of Precambrian thioredoxins and β-lactamases to experimentally address the change of site-specific amino acid preferences over long geological timescales. Extensive mutational analyses support the notion that evolutionary adjustment to a new amino acid may occur, but to a large extent this is insufficient to erase the primitive preference for amino acid replacements. Generally, site-specific amino acid preferences appear to remain conserved throughout evolutionary history despite local sequence divergence. We show such preference conservation to be readily understandable in molecular terms and we provide crystallographic evidence for an intriguing structural-switch mechanism: Energetic preference for an ancestral amino acid in a modern protein can be linked to reorganization upon mutation to the ancestral local structure around the mutated site. Finally, we point out that site-specific preference conservation naturally leads to one plausible evolutionary explanation for the existence of intragenic global suppressor mutations. PMID:25392342

  11. Feedback Solution to Optimal Switching Problems With Switching Cost.

    Science.gov (United States)

    Heydari, Ali

    2016-10-01

    The problem of optimal switching between nonlinear autonomous subsystems is investigated in this paper where the objective is not only bringing the states to close to the desired point, but also adjusting the switching pattern, in the sense of penalizing switching occurrences and assigning different preferences to utilization of different modes. The mode sequence is unspecified and a switching cost term is used in the cost function for penalizing each switching. It is shown that once a switching cost is incorporated, the optimal cost-to-go function depends on the subsystem which was active at the previous time step. Afterward, an approximate dynamic programming-based method is developed, which provides an approximation of the optimal solution to the problem in a feedback form and for different initial conditions. Finally, the performance of the method is analyzed through numerical examples.

  12. All-electric-controlled spin current switching in single-molecule magnet-tunnel junctions

    Institute of Scientific and Technical Information of China (English)

    Zhang Zheng-Zhong; Shen Rui; Sheng Li; Wang Rui-Qiang; Wang Bai-Gen; Xing Ding-Yu

    2011-01-01

    A single-molecule magnet (SMM)coupled to two normal metallic electrodes can both switch spin-up and spindown electronic currents within two different windows of SMM gate voltage. Such spin current switching in the SMM tunnel junction arises from spin-selected single electron resonant tunneling via the lowest unoccupied molecular orbit of the SMM. Since it is not magnetically controlled but all-electrically controlled, the proposed spin current switching effect may have potential applications in future spintronics.

  13. A Study of MPLS Hybrid Switch Based on ATM Switch

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    MPLS is the most successful integrating model of IP over ATM. The paper discusses some problems and their possible solutions when MPLS is supported by ATM switch. How to design the hardware, software and network management systems of such a switch device that has only one switching platform and one NMS but two sets of control planes at the same time, ATM and MPLS, is studied in details. The application of such a hybrid switch is presented in the last part of the paper.

  14. Composite Thermal Switch

    Science.gov (United States)

    McDonald, Robert; Brawn, Shelly; Harrison, Katherine; O'Toole, Shannon; Moeller, Michael

    2011-01-01

    Lithium primary and lithium ion secondary batteries provide high specific energy and energy density. The use of these batteries also helps to reduce launch weight. Both primary and secondary cells can be packaged as high-rate cells, which can present a threat to crew and equipment in the event of external or internal short circuits. Overheating of the cell interior from high current flows induced by short circuits can result in exothermic reactions in lithium primary cells and fully charged lithium ion secondary cells. Venting of the cell case, ejection of cell components, and fire have been reported in both types of cells, resulting from abuse, cell imperfections, or faulty electronic control design. A switch has been developed that consists of a thin layer of composite material made from nanoscale particles of nickel and Teflon that conducts electrons at room temperature and switches to an insulator at an elevated temperature, thus interrupting current flow to prevent thermal runaway caused by internal short circuits. The material is placed within the cell, as a thin layer incorporated within the anode and/or the cathode, to control excess currents from metal-to-metal or metal-to-carbon shorts that might result from cell crush or a manufacturing defect. The safety of high-rate cells is thus improved, preventing serious injury to personnel and sensitive equipment located near the battery. The use of recently available nanoscale particles of nickel and Teflon permits an improved, homogeneous material with the potential to be fine-tuned to a unique switch temperature, sufficiently below the onset of a catastrophic chemical reaction. The smaller particles also permit the formation of a thinner control film layer (switch (CTS(TradeMark)) coating can be incorporated in either the anode or cathode or both. The coating can be applied in a variety of different processes that permits incorporation in the cell and electrode manufacturing processes. The CTS responds quickly

  15. A computational study on the N-heterocyclic carbene-catalyzed Csp(2)-Csp(3) bond activation/[4+2] cycloaddition cascade reaction of cyclobutenones with imines: a new application of the conservation principle of molecular orbital symmetry.

    Science.gov (United States)

    Wang, Yang; Wu, Bohua; Zhang, Haoyang; Wei, Donghui; Tang, Mingsheng

    2016-07-20

    A comprehensive density functional theory (DFT) investigation has been performed to interrogate the mechanisms and stereoselectivities of the Csp(2)-Csp(3) single bond activation of cyclobutenones and their [4+2] cycloaddition reaction with imines via N-heterocyclic carbene (NHC) organocatalysis. According to our calculated results, the fundamental reaction pathway contains four steps: nucleophilic addition of NHC to cyclobutenone, C-C bond cleavage for the formation of an enolate intermediate, [4+2] cycloaddition of the enolate intermediate with isatin imine, and the elimination of the NHC catalyst. In addition, the calculated results also reveal that the second reaction step is the rate-determining step, whereas the third step is the regio- and stereo-selectivity determining step. For the regio- and stereo-selectivity determining step, all four possible attack modes were considered. The addition of the C[double bond, length as m-dash]N bond in isatin imine to the dienolate intermediate is more energy favorable than the addition of the C[double bond, length as m-dash]O bond to a dienolate intermediate. Moreover, the Re face addition of the C[double bond, length as m-dash]N bond in isatin imine to the Re face of the dienolate intermediate leading to the SS configuration N-containing product was demonstrated to be most energy favorable, which is mainly due to the stronger second-order perturbation energy value in the corresponding transition state. Furthermore, by tracking the frontier molecular orbital (FMO) changes in the rate-determining C-C bond cleavage step, we found that the reaction obeys the conservation principle of molecular orbital symmetry. We believe that the present work would provide valuable insights into this kind of reaction.

  16. Research Progress on Multimode Interference Switches

    Institute of Scientific and Technical Information of China (English)

    GAO Qing; SHENG Zhi-rui; JIANG Xiao-qing; WANG Ming-hua

    2005-01-01

    Optical switches are key components for constructing optical communication networks, so it is necessary to design optical switches and optical switch arrays with high performance and low cost. As one type of optical switches, the multimode interference(MMI) switches have received considerable attention due to their unique merits. The structures and operation principles of various types of MMI switches are introduced,and the recent progresses of MMI switches are also discussed.

  17. BolA is a transcriptional switch that turns off motility and turns on biofilm development.

    Science.gov (United States)

    Dressaire, Clémentine; Moreira, Ricardo Neves; Barahona, Susana; Alves de Matos, António Pedro; Arraiano, Cecília Maria

    2015-02-17

    Bacteria are extremely versatile organisms that rapidly adapt to changing environments. When bacterial cells switch from planktonic growth to biofilm, flagellum formation is turned off and the production of fimbriae and extracellular polysaccharides is switched on. BolA is present in most Gram-negative bacteria, and homologues can be found from proteobacteria to eukaryotes. Here, we show that BolA is a new bacterial transcription factor that modulates the switch from a planktonic to a sessile lifestyle. It negatively modulates flagellar biosynthesis and swimming capacity in Escherichia coli. Furthermore, BolA overexpression favors biofilm formation, involving the production of fimbria-like adhesins and curli. Our results also demonstrate that BolA is a protein with high affinity to DNA and is able to regulate many genes on a genome-wide scale. Moreover, we show that the most significant targets of this protein involve a complex network of genes encoding proteins related to biofilm development. Herein, we propose that BolA is a motile/adhesive transcriptional switch, specifically involved in the transition between the planktonic and the attachment stage of biofilm formation. Escherichia coli cells possess several mechanisms to cope with stresses. BolA has been described as a protein important for survival in late stages of bacterial growth and under harsh environmental conditions. BolA-like proteins are widely conserved from prokaryotes to eukaryotes. Although their exact function is not fully established at the molecular level, they seem to be involved in cell proliferation or cell cycle regulation. Here, we unraveled the role of BolA in biofilm development and bacterial motility. Our work suggests that BolA actively contributes to the decision of bacteria to arrest flagellar production and initiate the attachment to form structured communities, such as biofilms. The molecular studies of different lifestyles coupled with the comprehension of the BolA functions may

  18. Carbohydrate-based switch-on molecular sensor for Cu(II) in buffer: absorption and fluorescence study of the selective recognition of Cu(II) ions by galactosyl derivatives in HEPES buffer.

    Science.gov (United States)

    Singhal, Nitin Kumar; Ramanujam, Balaji; Mariappanadar, Vairamani; Rao, Chebrolu Pulla

    2006-08-03

    [graph: see text] 1-(Beta-D-galactopyranosyl-1'-deoxy-1'-iminomethyl)-2-hydroxynaphthalene (L1), possessing an ONO binding core, was found to be selective for Cu2+ ions in N-[2-hydroxyethyl]piperazine-N'-[2-ethanesulfonic acid] buffer, at concentrations < or = 580 ppb, at physiological pH by eliciting switch-on behavior, whereas the other ions, viz., Mg2+, Ca2+, Mn2+, Fe2+, Co2+, Ni2+, Zn2+, and Cd2+, caused no significant change in the fluorescence. Whereas the binding characteristics were ascertained by absorption spectroscopy, the species formed were shown by Q-TOF ES MS.

  19. Switching on the Aire conditioner.

    Science.gov (United States)

    Matsumoto, Mitsuru

    2015-12-01

    Aire has been cloned as the gene responsible for a hereditary type of organ-specific autoimmune disease. Aire controls the expression of a wide array of tissue-restricted Ags by medullary thymic epithelial cells (mTECs), thereby leading to clonal deletion and Treg-cell production, and ultimately to the establishment of self-tolerance. However, relatively little is known about the mechanism responsible for the control of Aire expression itself. In this issue of the European Journal of Immunology, Haljasorg et al. [Eur. J. Immunol. 2015. 45: 3246-3256] have reported the presence of an enhancer element for Aire that binds with NF-κB components downstream of the TNF receptor family member, RANK (receptor activator of NF-κB). The results suggest that RANK has a dual mode of action in Aire expression: one involving the promotion of mTEC differentiation and the other involving activation of the molecular switch for Aire within mature mTECs. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Bistable organic materials in optoelectrical switches: Two-electrode devices vs. organic field effect transistors

    CERN Document Server

    Sworakowski, Juliusz

    2011-01-01

    The paper presents a short overview of research into properties of organic materials and structures that could be used in optoelectrical switches, i.e., switches in which changes in electrical properties are triggered by light of appropriate wavelengths. In particular, described are the structures acting by virtue of reversible photochemical reactions occurring in photochromic molecular materials.

  1. Bistability in a metabolic network underpins the de novo evolution of colony switching in Pseudomonas fluorescens

    NARCIS (Netherlands)

    Gallie, J.; Libby, E.; Bertels, F.; Jendresen, C.B.; Martinussen, J.; Kilstrup, M.; Desprat, N.; Buffing, M.F.; Sauer, U.; Beaumont, H.J.E.; Rainey, P.B.

    2015-01-01

    Phenotype switching is commonly observed in nature. This prevalence has allowed the elucidation of a number of underlying molecular mechanisms. However, little is known about how phenotypic switches arise and function in their early evolutionary stages. The first opportunity to provide empirical

  2. Recent developments in switching theory

    CERN Document Server

    Mukhopadhyay, Amar

    2013-01-01

    Electrical Science Series: Recent Developments in Switching Theory covers the progress in the study of the switching theory. The book discusses the simplified proof of Post's theorem on completeness of logic primitives; the role of feedback in combinational switching circuits; and the systematic procedure for the design of Lupanov decoding networks. The text also describes the classical results on counting theorems and their application to the classification of switching functions under different notions of equivalence, including linear and affine equivalences. The development of abstract har

  3. Software Switching for Data Acquisition

    CERN Document Server

    CERN. Geneva; Malone, David

    2016-01-01

    In this talk we discuss the feasibility of replacing telecom-class routers with a topology of commodity servers acting as software switches in data acquisition. We extend the popular software switch, Open vSwitch, with a dedicated, throughput-oriented buffering mechanism. We compare the performance under heavy many-to-one congestion to typical Ethernet switches and evaluate the scalability when building larger topologies, exploiting the integration with software-defined networking technologies. Please note that David Malone will speak on behalf of Grzegorz Jereczek.

  4. Noise-induced coherent switch

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Taking the famous genetic toggle switch as an example,we numerically investigated the effect of noise on bistability.We found that extrinsic noise resulting from stochastic fluctuations in synthesis and degradation rates and from the environmental fluctuation in gene regulatory processes can induce coherent switch,and that there is an optimal noise intensity such that the noise not only can induce this switch,but also can amplify a weak input signal.In addition,we found that the intrinsic noise introduced through the Poisson τ-leap algorithm cannot induce such a switch.

  5. Low power all optical switches

    Institute of Scientific and Technical Information of China (English)

    Alireza Bananej; LI Chun-fei 李淳飞

    2004-01-01

    In this paper, we propose a new design of all fiber optical switches by using a high finesse ring resonator (RR) side coupled Mach-Zehnder interferometer. We will show that by compensating the total loss in the RR the switching power can be decreased greatly and by loss, compensating the bistability effect in RR can be cancelled and the switching performance can be improved. In addition, we will show that by using Erbium doped fiber for fabricating the RR we can obtain switching power threshold in mW range.

  6. Hemangiosarcoma after breast-conserving therapy of breast cancer. Report of four cases with molecular genetic diagnosis and literature review; Haemangiosarkom nach brusterhaltender Therapie beim Mammakarzinom. Vier Fallbeispiele mit molekulargenetischer Diagnostik und Literaturuebersicht

    Energy Technology Data Exchange (ETDEWEB)

    Nestle-Kraemling, Carolin [Universitaetsklinikum, Duesseldorf (Germany). Frauenklinik; Boelke, Edwin; Budach, Wilfried [Universitaetsklinikum Duesseldorf (DE). Klinik und Poliklinik fuer Strahlentherapie und radiologische Onkologie] (and others)

    2011-10-15

    Hemangiosarcomas of the breast represent a rare disease of the breast mainly occurring as secondary neoplasias with a latency of 5-10 years after primary treatment of breast cancer and are associated with an unfavourable prognosis. Radiation therapy, which is integrated within the concept of breast conserving therapy ranks as the main risk factor. In this report we describe the clinical course of 4 patients including their molecular genetic pattern and give a summary of the actual literature. Hemangiosarcomas occur as a secondary neoplasm with a latency of 5-10 years after primary treatment of breast cancer and have an unfavorable prognosis. A genetic predisposition is assumed, but we could not find a significant role of tumor suppressor genes BRCA1, BRCA2 or p53 in our patients. Due to limited data available for these tumors, recommendations for therapy include radical tumor resection achieving wide free margins and inconsistent regimens of chemo- and/or immunetherapy modalities. In the majority these are based on systemic therapy regimens for other cutaneous sarcomas, such as Kaposi's sarcoma. Efforts should be taken for a nation-wide systematic registration of all cases of post-irradiation hemangiosarcomas.

  7. Switching surface chemistry with supramolecular machines.

    Energy Technology Data Exchange (ETDEWEB)

    Dunbar, Timothy D.; Kelly, Michael James; Jeppesen, Jan O. (University of California, Los Angeles, CA); Bunker, Bruce Conrad; Matzke, Carolyn M.; Stoddart, J. Fraser; Huber, Dale L.; Kushmerick, James G.; Flood, Amar H. (University of California, Los Angeles, CA); Perkins, Julie (University of California, Los Angeles, CA); Cao, Jianguo (University of California, Los Angeles, CA)

    2005-07-01

    Tethered supramolecular machines represent a new class of active self-assembled monolayers in which molecular configurations can be reversibly programmed using electrochemical stimuli. We are using these machines to address the chemistry of substrate surfaces for integrated microfluidic systems. Interactions between the tethered tetracationic cyclophane host cyclobis(paraquat-p-phenylene) and dissolved {pi}-electron-rich guest molecules, such as tetrathiafulvalene, have been reversibly switched by oxidative electrochemistry. The results demonstrate that surface-bound supramolecular machines can be programmed to adsorb or release appropriately designed solution species for manipulating surface chemistry.

  8. Neuromorphic atomic switch networks.

    Directory of Open Access Journals (Sweden)

    Audrius V Avizienis

    Full Text Available Efforts to emulate the formidable information processing capabilities of the brain through neuromorphic engineering have been bolstered by recent progress in the fabrication of nonlinear, nanoscale circuit elements that exhibit synapse-like operational characteristics. However, conventional fabrication techniques are unable to efficiently generate structures with the highly complex interconnectivity found in biological neuronal networks. Here we demonstrate the physical realization of a self-assembled neuromorphic device which implements basic concepts of systems neuroscience through a hardware-based platform comprised of over a billion interconnected atomic-switch inorganic synapses embedded in a complex network of silver nanowires. Observations of network activation and passive harmonic generation demonstrate a collective response to input stimulus in agreement with recent theoretical predictions. Further, emergent behaviors unique to the complex network of atomic switches and akin to brain function are observed, namely spatially distributed memory, recurrent dynamics and the activation of feedforward subnetworks. These devices display the functional characteristics required for implementing unconventional, biologically and neurally inspired computational methodologies in a synthetic experimental system.

  9. Data center coolant switch

    Energy Technology Data Exchange (ETDEWEB)

    Iyengar, Madhusudan K.; Parida, Pritish R.; Schultz, Mark D.

    2015-10-06

    A data center cooling system is operated in a first mode; it has an indoor portion wherein heat is absorbed from components in the data center, and an outdoor heat exchanger portion wherein outside air is used to cool a first heat transfer fluid (e.g., water) present in at least the outdoor heat exchanger portion of the cooling system during the first mode. The first heat transfer fluid is a relatively high performance heat transfer fluid (as compared to the second fluid), and has a first heat transfer fluid freezing point. A determination is made that an appropriate time has been reached to switch from the first mode to a second mode. Based on this determination, the outdoor heat exchanger portion of the data cooling system is switched to a second heat transfer fluid, which is a relatively low performance heat transfer fluid, as compared to the first heat transfer fluid. It has a second heat transfer fluid freezing point lower than the first heat transfer fluid freezing point, and the second heat transfer fluid freezing point is sufficiently low to operate without freezing when the outdoor air temperature drops below a first predetermined relationship with the first heat transfer fluid freezing point.

  10. Dynamic chirality, chirality transfer and aggregation behaviour of dithienylethene switches

    NARCIS (Netherlands)

    de Jong, Jaap J. D.; van Rijn, Patrick; Tiemersma-Wegeman, Theodora D.; Lucas, Linda N.; Browne, Wesley R.; Kellogg, Richard M.; Uchida, Kingo; Van Esch, Jan H.; Feringa, Ben L.

    2008-01-01

    The synthesis and characterisation of a series of chiral and achiral low molecular weight organogelators (LMWGs) based on bis-amide substituted dithienylethene photochromic switches is reported. The LMWGs gelate a range of solvents depending on the specific functionalisation of the hydrogen bonding

  11. A continuous switching model for piezoelectric state switching methods

    Science.gov (United States)

    Lopp, Garrett K.; Kauffman, Jeffrey L.

    2017-04-01

    Piezoelectric-based, semi-active vibration reduction approaches have been studied for over a decade due to their potential in controlling vibration over a large frequency range. Previous studies have relied on a discrete model when switching between the stiffness states of the system. In such a modeling approach, the energy dissipation of the stored potential energy and the transient dynamics, in general, are not well understood. In this paper, a switching model is presented using a variable capacitance in the attached shunt circuit. When the switch duration is small in comparison to the period of vibration, the vibration reduction performance approaches that of the discrete model with an instantaneous switch, whereas longer switch durations lead to less vibration reduction. An energy analysis is then performed that results in the appearance of an energy dissipation term due to the varying capacitance in the shunt circuit.

  12. Hybrid switch for resonant power converters

    Science.gov (United States)

    Lai, Jih-Sheng; Yu, Wensong

    2014-09-09

    A hybrid switch comprising two semiconductor switches connected in parallel but having different voltage drop characteristics as a function of current facilitates attainment of zero voltage switching and reduces conduction losses to complement reduction of switching losses achieved through zero voltage switching in power converters such as high-current inverters.

  13. Incorporating Cobalt Carbonyl Moieties onto Ethynylthiophene-Based Dithienylcyclopentene Switches. 1. Photochemistry

    NARCIS (Netherlands)

    Harvey, Emma C.; Areephong, Jetsuda; Cafolla, Attilio A.; Long, Conor; Browne, Wesley R.; Pryce, Mary T.; Feringa, Bernard

    2014-01-01

    The synthesis and characterization of a series of dithienyl perhydro- and perfluorocyclopentene photochromic molecular switches appended with cobalt carbonyl binding 3-ethynylthiophene and phenyl-3-ethynylthiophene substituents are reported. Their photochromic properties, fatigue resistance, and the

  14. Incorporating Cobalt Carbonyl Moieties onto Ethynylthiophene-Based Dithienylcyclopentene Switches. 2. Electro- and Spectroelectrochernical Properties

    NARCIS (Netherlands)

    Harvey, Emma C.; Areephong, Jetsuda; Cafolla, Attilio A.; Long, Conor; Browne, Wesley R.; Feringa, Ben L.; Pryce, Mary T.

    2014-01-01

    The redox behavior of dithienyl perhydro- and perfluorocyclopentene photochromic molecular switches, modified with 3-ethynylthiophene and phenyl-3-ethynylthiophene substituents, is explored by cyclic voltammetry and UV/vis-NIR and IR spectroelectrochemistry. The extent of electrochemical oxidation i

  15. Mode initialization when simulating switched bond graphs, version II

    OpenAIRE

    Edström, Krister

    1998-01-01

    When simulating hybrid systems using switched bond graphs, the initialization of new modes is made by using a generalization of the principle of momentum conservation. Here it is shown how to use causality propagation to get an efficient initialization algorithm. By looking at causal paths, set of variables that have to be initialized simultaneously are found. Furthermore, it is shown how impulses due to structural changes in the system can be found with a correct initialization and with a co...

  16. A CMOS Switched Transconductor Mixer

    NARCIS (Netherlands)

    Klumperink, Eric A.M.; Louwsma, S.M.; Wienk, Gerhardus J.M.; Nauta, Bram

    A new CMOS active mixer topology can operate at low supply voltages by the use of switches exclusively connected to the supply voltages. Such switches require less voltage headroom and avoid gate-oxide reliability problems. Mixing is achieved by exploiting two transconductors with cross-coupled

  17. Seidel Switching and Graph Energy

    NARCIS (Netherlands)

    Haemers, W.H.

    2012-01-01

    Abstract: The energy of a graph Γ is the sum of the absolute values of the eigenvalues of the adjacency matrix of Γ. Seidel switching is an operation on the edge set of Γ. In some special cases Seidel switching does not change the spectrum, and therefore the energy. Here we investigate when Seidel s

  18. Molecule-Based Rheology Switching

    NARCIS (Netherlands)

    Paulusse, Jos M.J.; Sijbesma, Rint P.

    2006-01-01

    Sound-activated switching: The rheological behavior of fluids can be affected by external stimuli, as demonstrated by electrochemically and photochemically induced changes in viscosity and sol–gel transitions. Recently, ultrasound has emerged as a novel rheology switch for supramolecular polymers an

  19. Improved switch-resistor packaging

    Science.gov (United States)

    Redmerski, R. E.

    1980-01-01

    Packaging approach makes resistors more accessible and easily identified with specific switches. Failures are repaired more quickly because of improved accessibility. Typical board includes one resistor that acts as circuit breaker, and others are positioned so that their values can be easily measured when switch is operated. Approach saves weight by using less wire and saves valuable panel space.

  20. Battery switch for downhole tools

    Science.gov (United States)

    Boling, Brian E.

    2010-02-23

    An electrical circuit for a downhole tool may include a battery, a load electrically connected to the battery, and at least one switch electrically connected in series with the battery and to the load. The at least one switch may be configured to close when a tool temperature exceeds a selected temperature.

  1. Optimized scalable network switch

    Science.gov (United States)

    Blumrich, Matthias A.; Chen, Dong; Coteus, Paul W.

    2010-02-23

    In a massively parallel computing system having a plurality of nodes configured in m multi-dimensions, each node including a computing device, a method for routing packets towards their destination nodes is provided which includes generating at least one of a 2m plurality of compact bit vectors containing information derived from downstream nodes. A multilevel arbitration process in which downstream information stored in the compact vectors, such as link status information and fullness of downstream buffers, is used to determine a preferred direction and virtual channel for packet transmission. Preferred direction ranges are encoded and virtual channels are selected by examining the plurality of compact bit vectors. This dynamic routing method eliminates the necessity of routing tables, thus enhancing scalability of the switch.

  2. Multistable decision switches for flexible control of epigenetic differentiation.

    Directory of Open Access Journals (Sweden)

    Raúl Guantes

    2008-11-01

    Full Text Available It is now recognized that molecular circuits with positive feedback can induce two different gene expression states (bistability under the very same cellular conditions. Whether, and how, cells make use of the coexistence of a larger number of stable states (multistability is however largely unknown. Here, we first examine how autoregulation, a common attribute of genetic master regulators, facilitates multistability in two-component circuits. A systematic exploration of these modules' parameter space reveals two classes of molecular switches, involving transitions in bistable (progression switches or multistable (decision switches regimes. We demonstrate the potential of decision switches for multifaceted stimulus processing, including strength, duration, and flexible discrimination. These tasks enhance response specificity, help to store short-term memories of recent signaling events, stabilize transient gene expression, and enable stochastic fate commitment. The relevance of these circuits is further supported by biological data, because we find them in numerous developmental scenarios. Indeed, many of the presented information-processing features of decision switches could ultimately demonstrate a more flexible control of epigenetic differentiation.

  3. Optogenetic switches for light-controlled gene expression in yeast.

    Science.gov (United States)

    Salinas, Francisco; Rojas, Vicente; Delgado, Verónica; Agosin, Eduardo; Larrondo, Luis F

    2017-04-01

    Light is increasingly recognized as an efficient means of controlling diverse biological processes with high spatiotemporal resolution. Optogenetic switches are molecular devices for regulating light-controlled gene expression, protein localization, signal transduction and protein-protein interactions. Such molecular components have been mainly developed through the use of photoreceptors, which upon light stimulation undergo conformational changes passing to an active state. The current repertoires of optogenetic switches include red, blue and UV-B light photoreceptors and have been implemented in a broad spectrum of biological platforms. In this review, we revisit different optogenetic switches that have been used in diverse biological platforms, with emphasis on those used for light-controlled gene expression in the budding yeast Saccharomyces cerevisiae. The implementation of these switches overcomes the use of traditional chemical inducers, allowing precise control of gene expression at lower costs, without leaving chemical traces, and positively impacting the production of high-value metabolites and heterologous proteins. Additionally, we highlight the potential of utilizing this technology beyond laboratory strains, by optimizing it for use in yeasts tamed for industrial processes. Finally, we discuss how fungal photoreceptors could serve as a source of biological parts for the development of novel optogenetic switches with improved characteristics. Although optogenetic tools have had a strong impact on basic research, their use in applied sciences is still undervalued. Therefore, the invitation for the future is to utilize this technology in biotechnological and industrial settings.

  4. Amorphous metal based nanoelectromechanical switch

    KAUST Repository

    Mayet, Abdulilah M.

    2013-04-01

    Nanoelectromechanical (NEM) switch is an interesting ultra-low power option which can operate in the harsh environment and can be a complementary element in complex digital circuitry. Although significant advancement is happening in this field, report on ultra-low voltage (pull-in) switch which offers high switching speed and area efficiency is yet to be made. One key challenge to achieve such characteristics is to fabricate nano-scale switches with amorphous metal so the shape and dimensional integrity are maintained to achieve the desired performance. Therefore, we report a tungsten alloy based amorphous metal with fabrication process development of laterally actuated dual gated NEM switches with 100 nm width and 200 nm air-gap to result in <5 volts of actuation voltage (Vpull-in). © 2013 IEEE.

  5. grammatical constraints on intrasentential code switching

    African Journals Online (AJOL)

    www

    characterise another approach to code switching, namely a Minimalist ... la Virgen (God and the Virgin willing), as well as code switching involving set phrases .... switching is possible where the placement of adjectives and nouns obey both ...

  6. Conserved nematode signalling molecules elicit plant defenses and pathogen resistance

    OpenAIRE

    Manosalva, P; Manohar, M; von Reuss, S.; Chen, S.; Koch, A; Kaplan, F; Choe, A.; Micikas, R.; X. Wang; Kogel, K.; Sternberg, P.; Williamson, V; Schroeder, D; Klessig, F.

    2015-01-01

    Plant-defense responses are triggered by perception of conserved microbe-associated molecular patterns (MAMPs), for example, flagellin or peptidoglycan. However, it remained unknown whether plants can detect conserved molecular patterns derived from plant-parasitic animals, including nematodes. Here we show that several genera of plant-parasitic nematodes produce small molecules called ascarosides, an evolutionarily conserved family of nematode pheromones. Picomolar to micromolar concentratio...

  7. Spin state switching in iron coordination compounds

    Directory of Open Access Journals (Sweden)

    Philipp Gütlich

    2013-02-01

    Full Text Available The article deals with coordination compounds of iron(II that may exhibit thermally induced spin transition, known as spin crossover, depending on the nature of the coordinating ligand sphere. Spin transition in such compounds also occurs under pressure and irradiation with light. The spin states involved have different magnetic and optical properties suitable for their detection and characterization. Spin crossover compounds, though known for more than eight decades, have become most attractive in recent years and are extensively studied by chemists and physicists. The switching properties make such materials potential candidates for practical applications in thermal and pressure sensors as well as optical devices.The article begins with a brief description of the principle of molecular spin state switching using simple concepts of ligand field theory. Conditions to be fulfilled in order to observe spin crossover will be explained and general remarks regarding the chemical nature that is important for the occurrence of spin crossover will be made. A subsequent section describes the molecular consequences of spin crossover and the variety of physical techniques usually applied for their characterization. The effects of light irradiation (LIESST and application of pressure are subjects of two separate sections. The major part of this account concentrates on selected spin crossover compounds of iron(II, with particular emphasis on the chemical and physical influences on the spin crossover behavior. The vast variety of compounds exhibiting this fascinating switching phenomenon encompasses mono-, oligo- and polynuclear iron(II complexes and cages, polymeric 1D, 2D and 3D systems, nanomaterials, and polyfunctional materials that combine spin crossover with another physical or chemical property.

  8. Keep flexible - Keep switching! The influence of forced task switching on voluntary task switching.

    Science.gov (United States)

    Fröber, Kerstin; Dreisbach, Gesine

    2017-05-01

    Goal directed behavior depends on a dynamic balance between cognitive flexibility and stability. Identifying factors that modulate the balance between these control states is therefore of major interest for the understanding of human action control. In two experiments we used a hybrid paradigm combining forced- and free-choice task switching and measured spontaneous voluntary switch rate (VSR) as an indicator of cognitive flexibility. In Experiment 1 participants were free to choose a given task on 75%, 50%, or 25% of all trials. In the remaining forced-choice trials task repetitions and switches were roughly equally distributed. Results showed that VSR increases with increasing proportion of forced choices. To clarify whether the frequency of forced choices per se or the frequency of forced task switches in particular drives this effect we conducted Experiment 2. In a fully orthogonal between design participants were free to choose a given task on 75% or 25% of all trials with a predetermined switch rate in the remaining forced-choice trials of 75% or 25%, respectively. Results revealed an interaction of both manipulations: The highest VSR was found for the combination of 75% forced-choice trials with 75% forced switch rate, while VSR for 75% forced-choice trials with 25% forced switch rate was still higher than VSRs in both conditions with 25% forced-choice trials. This suggests that a context of frequent forced task switching changes global control parameters towards more flexible behavior. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Model Reduction of Switched Systems Based on Switching Generalized Gramians

    DEFF Research Database (Denmark)

    Shaker, Hamid Reza; Wisniewski, Rafal

    2012-01-01

    In this paper, a general method for model order reduction of discrete-time switched linear systems is presented. The proposed technique uses switching generalized gramians. It is shown that several classical reduction methods can be developed into the generalized gramian framework for the model r......-Galerkin projection is constructed instead of the similarity transform approach for reduction. It is proven that the proposed reduction framework preserves the stability of the original switched system. The performance of the method is illustrated by numerical examples....

  10. Decision maker based on atomic switches

    Directory of Open Access Journals (Sweden)

    Song-Ju Kim

    2016-02-01

    Full Text Available We propose a simple model for an atomic switch-based decision maker (ASDM, and show that, as long as its total number of metal atoms is conserved when coupled with suitable operations, an atomic switch system provides a sophisticated ``decision-making'' capability that is known to be one of the most important intellectual abilities in human beings. We considered a popular decision-making problem studied in the context of reinforcement learning, the multi-armed bandit problem (MAB; the problem of finding, as accurately and quickly as possible, the most profitable option from a set of options that gives stochastic rewards. These decisions are made as dictated by each volume of precipitated metal atoms, which is moved in a manner similar to the fluctuations of a rigid body in a tug-of-war game. The ``tug-of-war (TOW dynamics'' of the ASDM exhibits higher efficiency than conventional reinforcement-learning algorithms. We show analytical calculations that validate the statistical reasons for the ASDM to produce such high performance, despite its simplicity. Efficient MAB solvers are useful for many practical applications, because MAB abstracts a variety of decision-making problems in real-world situations where an efficient trial-and-error is required. The proposed scheme will open up a new direction in physics-based analog-computing paradigms, which will include such things as ``intelligent nanodevices'' based on self-judgment.

  11. Self-assembly, Dynamics and Chirality of Conformational Switches on Metal Surfaces Studied by UHV-STM

    DEFF Research Database (Denmark)

    Nuermaimaiti, Ajiguli

    2013-01-01

    Molecular self-assembly is essential in the bottom-up design of nanostructures. Molecular conformational switches are highly interesting both from the basic science of view to enhance our understanding of molecular dynamics in adsorption systems, and also due to potential applications such as mol......Molecular self-assembly is essential in the bottom-up design of nanostructures. Molecular conformational switches are highly interesting both from the basic science of view to enhance our understanding of molecular dynamics in adsorption systems, and also due to potential applications...... structures formed by the conformational switches and statistical analysis of conformational states, a detailed study of dynamic processes is performed by acquiring time-resolved STM data. Furthermore, one of the possible applications of conformational switches towards inducing chirality in surface assemblies...

  12. Influence of the conserved disulphide bond, exposed to the putative binding pocket, on the structure and function of the immunoglobulin-like molecular chaperone Caf1M of Yersinia pestis.

    Science.gov (United States)

    Zav'yalov, V P; Chernovskaya, T V; Chapman, D A; Karlyshev, A V; MacIntyre, S; Zavialov, A V; Vasiliev, A M; Denesyuk, A I; Zav'yalova, G A; Dudich, I V; Korpela, T; Abramov, V M

    1997-06-01

    The Yersinia pestis protein Caf1M is a typical representative of a subfamily of periplasmic molecular chaperones with characteristic structural and functional features, one of which is the location of two conserved cysteine residues close to the putative binding pocket. We show that these residues form a disulphide bond, the reduction and alkylation of which significantly increases the dissociation constant of the Caf1M-Caf1 (where Caf 1 is a polypeptide subunit of the capsule) complex [from a Kd of (4.77+/-0.50)x10(-9) M for the intact protein to one of (3.68+/-0.68)x10(-8) M for the modified protein]. The importance of the disulphide bond for the formation of functional Caf1M in vivo was demonstrated using an Escherichia coli dsbA mutant carrying the Y. pestis f1 operon. In accordance with the CD and fluorescence measurements, the disulphide bond is not important for maintenance of the overall structure of the Caf1M molecule, but would appear to affect the fine structural properties of the subunit binding site. A three-dimensional model of the Caf1M-Caf1 complex was designed based on the published crystal structure of PapD (a chaperone required for Pap pili assembly) complexed with a peptide corresponding to the C-terminus of the papG subunit. In the model the disulphide bond is in close proximity to the invariant Caf1M Arg-23 and Lys-142 residues that are assumed to anchor the C-terminal group of the subunit. The importance of this characteristic disulphide bond for the orchestration of the binding site and subunit binding, as well as for the folding of the protein in vivo, is likely to be a common feature of this subfamily of Caf1M-like chaperones. A possible model for the role of the disulphide bond in Caf1 assembly is discussed.

  13. A conservative region of the mercuric reductase gene (merA as a molecular marker of bacterial mercury resistance Região conservada do gene da mercúrio redutase (merA como marcador molecular da resistência bacteriana ao mercúrio

    Directory of Open Access Journals (Sweden)

    Adriana Sotero-Martins

    2008-06-01

    Full Text Available The most common bacterial mercury resistance mechanism is based on the reduction of Hg(II to Hg0, which is dependent of the mercuric reductase enzyme (MerA activity. The use of a 431 bp fragment of a conservative region of the mercuric reductase (merA gene was applied as a molecular marker of this mechanism, allowing the identification of mercury resistant bacterial strains.O mecanismo de resistência bacteriana ao mercúrio mais comum é baseada na redução do Hg(II a Hg0, através da atividade da enzima mercúrio redutase (MerA. O uso do fragmento de 431 pb amplificado de uma região conservada do gene merA, que codifica a enzima MerA,foi utilizado como marcador molecular deste mecanismo, permitindo a identificação de bactérias resistentes ao mercúrio.

  14. Cell Fate Switch during In Vitro Plant Organogenesis

    Institute of Scientific and Technical Information of China (English)

    Xiang Yu Zhao; Ying Hua Su; Zhi Juan Cheng; Xian Sheng Zhang

    2008-01-01

    Plant mature cells have the capability to reverse their state of differenUation and produce new organs under cultured conditions. Two phases, dedifferentiation and redifferentiation, are commonly characterized during in vitro organogenesis.In these processes, cells undergo fate switch several times regulated by both extrinsic and intrinsic factors, which are associated with reentry to the cell cycle, the balance between euchromatin and heterochromatin, reprogramming of gene expression, and so forth. This short article reviews the advances in the mechanism of organ regeneration from plant somatic cells in molecular, genomic and epigenetic aspects, aiming to provide important information on the mechanism underlying cell fate switch during in vitro plant organogenesis.

  15. The Conservation Status and Conservation Strategy of Picea neoveitchii

    Institute of Scientific and Technical Information of China (English)

    Zhang Deshun; Kim Yongshik; Mike Maunder; Li Xiufen

    2006-01-01

    Picea neoveitchii is an endemic species in China. It had been listed as an endangered species in red data books. It scatters in several locations of south slope of the Qinling Mountain of China. Upon reviewing the related literature, discussing with leading scholars on gymnosperm, ecology and plant conservation, the field survey was carried out in four locations. There are eleven mature individuals and two seedlings surviving in its natural habitats. With the survey of quadrat method in four locations, related community index were calculated such as relative important value (RIV), species richness,similarity index, diversity index and evenness index etc.The community could be sorted and characterized as three groups based on the community parameters. The analysis of vegetation table elucidates that Picea neoveitchii is a dominant species with low grouping rate in most surveyed sites.The RAPD analysis shows target species has intraspecific genetic variability. The estimation of Shannon's phenotypic diversity index (Ho) also explains the difference of genetic variations of different locations.Due to the lack of enough knowledge and professional guide of conservation biological perspective,Picea neoveitchii had been clear-cut for timber production. The extent of occurrence and area of occupancy declined rapidly from 1950s to 1990s.According to the Conservation Category guideline proposed by the World Conservation Union, the conservation status of Picea neoveitchii was reevaluated as Critically Endangered (CR) B2b C2a D. Upon research in areas of ecology, molecular biology, cluster analysis of environmental parameters, a practical conservation strategy is recommended in this research.

  16. Tuning the Temperature Dependence for Switching in Dithienylethene Photochromic Switches

    NARCIS (Netherlands)

    Kudernac, Tibor; Kobayashi, Takao; Uyama, Ayaka; Uchida, Kingo; Nakamura, Shinichiro; Feringa, Ben L.

    2013-01-01

    Diarylethene photochromic switches use light to drive structural changes through reversible electrocyclization reactions. High efficiency in dynamic photoswitching is a prerequisite for applications, as is thermal stability and the selective addressability of both isomers ring-opened and -closed dia

  17. Switching Processes in Queueing Models

    CERN Document Server

    Anisimov, Vladimir V

    2008-01-01

    Switching processes, invented by the author in 1977, is the main tool used in the investigation of traffic problems from automotive to telecommunications. The title provides a new approach to low traffic problems based on the analysis of flows of rare events and queuing models. In the case of fast switching, averaging principle and diffusion approximation results are proved and applied to the investigation of transient phenomena for wide classes of overloading queuing networks.  The book is devoted to developing the asymptotic theory for the class of switching queuing models which covers  mode

  18. Electrically switched ion exchange

    Energy Technology Data Exchange (ETDEWEB)

    Lilga, M.A. [Pacific Northwest National Lab., Richland, WA (United States); Schwartz, D.T.; Genders, D.

    1997-10-01

    A variety of waste types containing radioactive {sup 137}Cs are found throughout the DOE complex. These waste types include water in reactor cooling basins, radioactive high-level waste (HLW) in underground storage tanks, and groundwater. Safety and regulatory requirements and economics require the removal of radiocesium before these wastes can be permanently disposed of. Electrically Switched Ion Exchange (ESIX) is an approach for radioactive cesium separation that combines IX and electrochemistry to provide a selective, reversible, and economic separation method that also produces little or no secondary waste. In the ESIX process, an electroactive IX film is deposited electrochemically onto a high-surface area electrode, and ion uptake and elution are controlled directly by modulating the potential of the film. For cesium, the electroactive films under investigation are ferrocyanides, which are well known to have high selectivities for cesium in concentrated sodium solutions. When a cathode potential is applied to the film, Fe{sup +3} is reduced to the Fe{sup +2} state, and a cation must be intercalated into the film to maintain charge neutrality (i.e., Cs{sup +} is loaded). Conversely, if an anodic potential is applied, a cation must be released from the film (i.e., Cs{sup +} is unloaded). Therefore, to load the film with cesium, the film is simply reduced; to unload cesium, the film is oxidized.

  19. Ligand binding and micro-switches in 7TM receptor structures

    DEFF Research Database (Denmark)

    Nygaard, Rie; Frimurer, Thomas M; Holst, Birgitte;

    2009-01-01

    ' in which extracellular loop 2b, in particular, functions as a gating element. Small-molecule antagonists and inverse agonists bind in very different modes: some very deeply and others more superficially, even reaching out above the transmembranes. Several highly conserved residues seem to function as micro......-switches of which ArgIII:26 (Arg3.50) in its active conformation interacts directly with the G protein. These micro-switches together with a hydrogen-bond network between conserved polar residues and structural water molecules are proposed to constitute an extended allosteric interface between the domains (i...

  20. Multispecies genetic objectives in spatial conservation planning.

    Science.gov (United States)

    Nielsen, Erica S; Beger, Maria; Henriques, Romina; Selkoe, Kimberly A; von der Heyden, Sophie

    2016-12-07

    The growing threats to biodiversity and global alteration of habitats and species distributions make it increasingly necessary to consider evolutionary patterns in conservation decision-making. Yet there is no clear-cut guidance on how genetic features can be incorporated into conservation planning processes, with multiple molecular markers and several genetic metrics for each marker type to choose from. Genetic patterns also differ between species, but the potential trade-offs amongst genetic objectives for multiple species in conservation planning are currently understudied. This study compares spatial conservation prioritizations derived from two metrics of both genetic diversity (nucleotide and haplotype diversity) and genetic isolation (private haplotypes and local genetic differentiation) for mitochondrial DNA for five marine species. The findings show that conservation plans based solely on habitat representation noticeably differ from those additionally including genetic data, with habitat-based conservation plans selecting fewer conservation priority areas. Furthermore, all four genetic metrics selected approximately similar conservation priority areas, which is likely a result of prioritizing genetic patterns across a genetically diverse array of species. Largely, the results suggest that multi-species genetic conservation objectives are vital to create protected area networks that appropriately preserve community-level evolutionary patterns. This article is protected by copyright. All rights reserved.

  1. Wide Bandgap Extrinsic Photoconductive Switches

    Energy Technology Data Exchange (ETDEWEB)

    Sullivan, James S. [State Univ. of New York (SUNY), Plattsburgh, NY (United States); Univ. of California, Davis, CA (United States)

    2012-01-20

    Photoconductive semiconductor switches (PCSS) have been investigated since the late 1970s. Some devices have been developed that withstand tens of kilovolts and others that switch hundreds of amperes. However, no single device has been developed that can reliably withstand both high voltage and switch high current. Yet, photoconductive switches still hold the promise of reliable high voltage and high current operation with subnanosecond risetimes. Particularly since good quality, bulk, single crystal, wide bandgap semiconductor materials have recently become available. In this chapter we will review the basic operation of PCSS devices, status of PCSS devices and properties of the wide bandgap semiconductors 4H-SiC, 6H-SiC and 2H-GaN.

  2. Industry switching in developing countries

    DEFF Research Database (Denmark)

    Newman, Carol; Rand, John; Tarp, Finn

    2013-01-01

    established entrants and exiting firms that are closing down operations. In this study, we develop an empirical model that examines switching behavior using data from Vietnamese manufacturing firms during the 2001–2008 period. The diagnostic shows that switching firms exhibit different characteristics......Firm turnover (i.e., firm entry and exit) is a well-recognized source of sector-level productivity growth. In contrast, the role and importance of firms that switch activities from one sector to another is not well understood. Firm switchers are likely to be unique, differing from both newly...... and behavior than do entry and exit firms. Switchers tend to be labor intensive and to seek competitive opportunities in labor-intensive sectors in response to changes in market environments. Moreover, resource reallocation resulting from switching forms an important component of productivity growth. The topic...

  3. The Allosteric Switching Mechanism in Bacteriophage MS2

    CERN Document Server

    Perkett, Matthew R

    2015-01-01

    In this article we use all-atom simulations to elucidate the mechanisms underlying conformational switching and allostery within the coat protein of the bacteriophage MS2. Assembly of most icosahedral virus capsids requires that the capsid protein adopt different conformations at precise locations within the capsid. It has been shown that a 19 nucleotide stem loop (TR) from the MS2 genome acts as an allosteric effector, guiding conformational switching of the coat protein during capsid assembly. Since the principal conformational changes occur far from the TR binding site, it is important to understand the molecular mechanism underlying this allosteric communication. To this end, we use all-atom simulations with explicit water combined with a path sampling technique to sample the MS2 coat protein conformational transition, in the presence and absence of TR-binding. The calculations find that TR binding strongly alters the transition free energy profile, leading to a switch in the favored conformation. We disc...

  4. A Piezoelectric Cryogenic Heat Switch

    Science.gov (United States)

    Jahromi, Amir E.; Sullivan, Dan F.

    2014-01-01

    We have measured the thermal conductance of a mechanical heat switch actuated by a piezoelectric positioner, the PZHS (PieZo electric Heat Switch), at cryogenic temperatures. The thermal conductance of the PZHS was measured between 4 K and 10 K, and on/off conductance ratios greater than 100 were achieved when the positioner applied its maximum force of 8 N. We discuss the advantages of using this system in cryogenic applications, and estimate the ultimate performance of an optimized PZHS.

  5. High PRF high current switch

    Science.gov (United States)

    Moran, Stuart L.; Hutcherson, R. Kenneth

    1990-03-27

    A triggerable, high voltage, high current, spark gap switch for use in pu power systems. The device comprises a pair of electrodes in a high pressure hydrogen environment that is triggered by introducing an arc between one electrode and a trigger pin. Unusually high repetition rates may be obtained by undervolting the switch, i.e., operating the trigger at voltages much below the self-breakdown voltage of the device.

  6. Magnetically insulated opening switch research

    Science.gov (United States)

    McGeoch, M. W.; Kraft, R.

    1987-01-01

    We examine the feasibility of an opening switch concept based on magnetic insulation in a coaxial thermionic diode. It is found that the impedance ratio between closed and open states of the diode is marginal for efficient energy transfer via this type of switch. The open, or insulated state of the diode is characterized by current leakage across the magnetic field which is associated with the presence of plasma waves.

  7. Meeting global conservation challenges

    Science.gov (United States)

    2016-10-01

    Hot on the heels of last year's Sustainable Development Goals and the Paris Agreement, representatives from the global conservation community met to set the conservation agenda that will help to implement these targets.

  8. Conservation: Threatened by Luxury.

    Science.gov (United States)

    Webb, Thomas J

    2016-06-20

    When animals are traded in lucrative international luxury markets, individuals really do matter to conservation. Identifying the intrinsic and extrinsic factors that make some species especially vulnerable to this kind of threat helps set guidelines for more effective conservation.

  9. K-Band Latching Switches

    Science.gov (United States)

    Piotrowski, W. S.; Raue, J. E.

    1984-01-01

    Design, development, and tests are described for two single-pole-double-throw latching waveguide ferrite switches: a K-band switch in WR-42 waveguide and a Ka-band switch in WR-28 waveguide. Both switches have structurally simple junctions, mechanically interlocked without the use of bonding materials; they are impervious to the effects of thermal, shock, and vibration stresses. Ferrite material for the Ka-band switch with a proper combination of magnetic and dielectric properties was available and resulted in excellent low loss, wideband performance. The high power handling requirement of the K-band switch limited the choice of ferrite to nickel-zinc compositions with adequate magnetic properties, but with too low relative dielectric constant. The relative dielectric constant determines the junction dimensions for given frequency responses. In this case the too low value unavoidably leads to a larger than optimum junction volume, increasing the insertion loss and restricting the operating bandwidth. Efforts to overcome the materials-related difficulties through the design of a composite junction with increased effective dielectric properties efforts to modify the relative dielectric constant of nickel-zinc ferrite are examined.

  10. K-band latching switches

    Science.gov (United States)

    Piotrowski, W. S.; Raue, J. E.

    1984-05-01

    Design, development, and tests are described for two single-pole-double-throw latching waveguide ferrite switches: a K-band switch in WR-42 waveguide and a Ka-band switch in WR-28 waveguide. Both switches have structurally simple junctions, mechanically interlocked without the use of bonding materials; they are impervious to the effects of thermal, shock, and vibration stresses. Ferrite material for the Ka-band switch with a proper combination of magnetic and dielectric properties was available and resulted in excellent low loss, wideband performance. The high power handling requirement of the K-band switch limited the choice of ferrite to nickel-zinc compositions with adequate magnetic properties, but with too low relative dielectric constant. The relative dielectric constant determines the junction dimensions for given frequency responses. In this case the too low value unavoidably leads to a larger than optimum junction volume, increasing the insertion loss and restricting the operating bandwidth. Efforts to overcome the materials-related difficulties through the design of a composite junction with increased effective dielectric properties efforts to modify the relative dielectric constant of nickel-zinc ferrite are examined.

  11. Conservation Action Handbook.

    Science.gov (United States)

    National Rifle Association, Washington, DC.

    Conservation problems are identified, with some suggestions for action. General areas covered are: Wildlife Conservation, Soil Conservation, Clean Water, Air Pollution Action, and Outdoor Recreation Action. Appendices list private organizations or agencies concerned with natural resource use and/or management, congressional committees considering…

  12. Quadratic stabilization of switched nonlinear systems

    Institute of Scientific and Technical Information of China (English)

    DONG YaLi; FAN JiaoJiao; MEI ShengWei

    2009-01-01

    In this paper, the problem of quadratic stabilization of multi-input multi-output switched nonlinear systems under an arbitrary switching law is investigated. When switched nonlinear systems have uniform normal form and the zero dynamics of uniform normal form is asymptotically stable under an arbitrary switching law, state feedbacks are designed and a common quadratic Lyapunov function of all the closed-loop subsystems is constructed to realize quadratic stabilizability of the class of switched nonlinear systems under an arbitrary switching law. The results of this paper are also applied to switched linear systems.

  13. Principles of broadband switching and networking

    CERN Document Server

    Liew, Soung C

    2010-01-01

    An authoritative introduction to the roles of switching and transmission in broadband integrated services networks Principles of Broadband Switching and Networking explains the design and analysis of switch architectures suitable for broadband integrated services networks, emphasizing packet-switched interconnection networks with distributed routing algorithms. The text examines the mathematical properties of these networks, rather than specific implementation technologies. Although the pedagogical explanations in this book are in the context of switches, many of the fundamenta

  14. Exactly conservation integrators

    Energy Technology Data Exchange (ETDEWEB)

    Shadwick, B.A.; Bowman, J.C.; Morrison, P.J. [Univ. of Texas, Austin, TX (United States)

    1999-03-01

    Traditional explicit numerical discretizations of conservative systems generically predict artificial secular drifts of any nonlinear invariants. In this work the authors present a general approach for developing explicit nontraditional algorithms that conserve such invariants exactly. They illustrate the method by applying it to the three-wave truncation of the Euler equations, the Lotka-Volterra predator-prey model, and the Kepler problem. The ideas are discussed in the context of symplectic (phase-space-conserving) integration methods as well as nonsymplectic conservative methods. They comment on the application of the method to general conservative systems.

  15. Exactly conservative integrators

    Energy Technology Data Exchange (ETDEWEB)

    Shadwick, B.A.; Bowman, J.C.; Morrison, P.J.

    1995-07-19

    Traditional numerical discretizations of conservative systems generically yield an artificial secular drift of any nonlinear invariants. In this work we present an explicit nontraditional algorithm that exactly conserves invariants. We illustrate the general method by applying it to the Three-Wave truncation of the Euler equations, the Volterra-Lotka predator-prey model, and the Kepler problem. We discuss our method in the context of symplectic (phase space conserving) integration methods as well as nonsymplectic conservative methods. We comment on the application of our method to general conservative systems.

  16. Exactly conservative integrators

    CERN Document Server

    Shadwick, B A; Morrison, P J; Bowman, John C

    1995-01-01

    Traditional numerical discretizations of conservative systems generically yield an artificial secular drift of any nonlinear invariants. In this work we present an explicit nontraditional algorithm that exactly conserves these invariants. We illustrate the general method by applying it to the three-wave truncation of the Euler equations, the Lotka--Volterra predator--prey model, and the Kepler problem. This method is discussed in the context of symplectic (phase space conserving) integration methods as well as nonsymplectic conservative methods. We comment on the application of our method to general conservative systems.

  17. Exactly conservative integrators

    Energy Technology Data Exchange (ETDEWEB)

    Shadwick, B.A.; Bowman, J.C.; Morrison, P.J.

    1995-07-19

    Traditional numerical discretizations of conservative systems generically yield an artificial secular drift of any nonlinear invariants. In this work we present an explicit nontraditional algorithm that exactly conserves invariants. We illustrate the general method by applying it to the Three-Wave truncation of the Euler equations, the Volterra-Lotka predator-prey model, and the Kepler problem. We discuss our method in the context of symplectic (phase space conserving) integration methods as well as nonsymplectic conservative methods. We comment on the application of our method to general conservative systems.

  18. Switchable molecular magnets.

    Science.gov (United States)

    Sato, Osamu

    2012-01-01

    Various molecular magnetic compounds whose magnetic properties can be controlled by external stimuli have been developed, including electrochemically, photochemically, and chemically tunable bulk magnets as well as a phototunable antiferromagnetic phase of single chain magnet. In addition, we present tunable paramagnetic mononuclear complexes ranging from spin crossover complexes and valence tautomeric complexes to Co complexes in which orbital angular momentum can be switched. Furthermore, we recently developed several switchable clusters and one-dimensional coordination polymers. The switching of magnetic properties can be achieved by modulating metals, ligands, and molecules/ions in the second sphere of the complexes.

  19. High power solid state switches

    Science.gov (United States)

    Gundersen, Martin

    1991-11-01

    We have successfully produced an optically triggered thyristor based in Gallium Arsenide, developed a model for breakdown, and are developing two related devices, including a Gallium Arsenide based static inductor thyristor. We are getting at the basic limitations of Gallium Arsenide for these applications, and are developing models for the physical processes that will determine device limitations. The previously supported gas phase work - resulting in the back-lighted thyratron (BLT) - has actually resulted in a very changed view of how switching can be accomplished, and this is impacting the design of important machines. The BLT is being studied internationally: in Japan for laser fusion and laser isotope separation. ITT has built a BLT that has switched 30 kA at 60 kV in testing at NSWC Dahlgren and the device is being commercialized by another American company. Versions of the switch are now being tested for excimer laser and other applications. Basically, the switch, which arose from pulse power physics studies at USC, can switch more current faster (higher di/dt), with less housekeeping, and with other advantageous properties. There are a large number of other new applications, include kinetic energy weapons, pulsed microwave sources and R.F. accelerators.

  20. Switching Systems: Active Mode Recognition, Identification of the Switching Law

    OpenAIRE

    Elom Ayih Domlan; José Ragot; Didier Maquin

    2007-01-01

    http://www.hindawi.com/journals/jcse/raa.50796.html; International audience; The problem of the estimation of the discrete state of a switching system is studied. The knowledge of the switching law is essential for this kind of system as it simplifies their manipulation for control purposes. This paper investigates the use of a model-based disgnosis method for the determination of the active mode at each timepoint based on the system input/output data. The issue of the parametric identificati...

  1. Máquinas Moleculares Artificiais

    OpenAIRE

    Mariana F. A. N. Guterres; Celia M. Ronconi

    2009-01-01

    The past decade has seen a dramatic increase in the number and structural/functional complexity of the artificial molecular machines that have been designed. In particular, numerous improvements in the construction procedures have led to the development of molecular switches, nanovalves, molecular muscles, nanoelevators, and rotary motors powered by photochemical, chemical, and electrochemical energy. The aim of this work is to discuss the basic principles involved in the construction of arti...

  2. Improvement on Switching Characteristics and Switching Losses of IGBT by ZVS—PWM①

    Institute of Scientific and Technical Information of China (English)

    ZHANGChunjiang; GUHerong; 等

    1997-01-01

    The principle of ZVS-PWM inverting circuit is first described by means of inverting welder supply.The contrastive study is made on switching characteristics and switching losses of IGBT between ZVS-PWM and hard-switching.

  3. Nonlinear switching and solitons in PT-symmetric photonic systems

    CERN Document Server

    Suchkov, Sergey V; Huang, Jiahao; Dmitriev, Sergey V; Lee, Chaohong; Kivshar, Yuri S

    2015-01-01

    One of the challenges of the modern photonics is to develop all-optical devices enabling increased speed and energy efficiency for transmitting and processing information on an optical chip. It is believed that the recently suggested Parity-Time (PT) symmetric photonic systems with alternating regions of gain and loss can bring novel functionalities. In such systems, losses are as important as gain and, depending on the structural parameters, gain compensates losses. Generally, PT systems demonstrate nontrivial non-conservative wave interactions and phase transitions, which can be employed for signal filtering and switching, opening new prospects for active control of light. In this review, we discuss a broad range of problems involving nonlinear PT-symmetric photonic systems with an intensity-dependent refractive index. Nonlinearity in such PT symmetric systems provides a basis for many effects such as the formation of localized modes, nonlinearly-induced PT-symmetry breaking, and all-optical switching. Nonl...

  4. Multiple switches in G protein-coupled receptor activation.

    Science.gov (United States)

    Ahuja, Shivani; Smith, Steven O

    2009-09-01

    The activation mechanism of G protein-coupled receptors has presented a puzzle that finally may be close to solution. These receptors have a relatively simple architecture consisting of seven transmembrane helices that contain just a handful of highly conserved amino acids, yet they respond to light and a range of chemically diverse ligands. Recent NMR structural studies on the active metarhodopsin II intermediate of the visual receptor rhodopsin, along with the recent crystal structure of the apoprotein opsin, have revealed multiple structural elements or 'switches' that must be simultaneously triggered to achieve full activation. The confluence of several required structural changes is an example of "coincidence counting", which is often used by nature to regulate biological processes. In ligand-activated G protein-coupled receptors, the presence of multiple switches may provide an explanation for the differences between full, partial and inverse agonists.

  5. Electro-optical switching by liquid-crystal controlled metasurfaces

    CERN Document Server

    Decker, Manuel; Minovich, Alexander; Staude, Isabelle; Miroshnichenko, Andrey E; Chigrin, Dmitry; Neshev, Dragomir N; Jagadish, Chennupati; Kivshar, Yuri S

    2013-01-01

    We study the optical response of a metamaterial surface created by a lattice of split-ring resonators covered with a nematic liquid crystal and demonstrate millisecond timescale switching between electric and magnetic resonances of the metasurface. This is achieved due to a high sensitivity of liquid-crystal molecular reorientation to the symmetry of the metasurface as well as to the presence of a bias electric field. Our experiments are complemented by numerical simulations of the liquid-crystal reorientation.

  6. Fission yeast mating-type switching: programmed damage and repair

    DEFF Research Database (Denmark)

    Egel, Richard

    2005-01-01

    . This discontinuity then remains protected for a full cell cycle, until it interferes with replication in the next S-phase. It, thereby, represents a valuable model system to study the molecular safeguards to protect a replication fork at a predetermined hindrance to leading-strand extension. The versatility...... of this experimental system has increased further yet by the recent development of a conditional setup, where imprinting and switching can be repressed or derepressed in response to external stimuli....

  7. Temperature switching of cavity modes in InN microcrystals

    Energy Technology Data Exchange (ETDEWEB)

    Kazanov, D. R., E-mail: kazanovdr@gmail.com; Kaibyshev, V. H.; Davydov, V. Yu.; Smirnov, A. N.; Jmerik, V. N.; Kuznetsova, N. V.; Kopiev, P. S.; Ivanov, S. V.; Shubina, T. V. [Russian Academy of Sciences, Ioffe Physical–Technical Institute (Russian Federation)

    2015-11-15

    InN optical cavities supporting low-order whispering-gallery modes up to room temperature are formed by molecular-beam epitaxy on patterned substrates. The observed switching of the mode type with increasing temperature is explained in terms of changes in the optical parameters due to a shift of the absorption edge and modification of its shape. Modeling taking into account a variation in the refractive index reproduces the typical distributions of the electromagnetic-field intensity in the cavities.

  8. Anti-tumor activity of splice-switching oligonucleotides

    OpenAIRE

    Bauman, John A; Li, Shyh-Dar; Yang, Angela; Huang, Leaf; Kole, Ryszard

    2010-01-01

    Alternative splicing has emerged as an important target for molecular therapies. Splice-switching oligonucleotides (SSOs) modulate alternative splicing by hybridizing to pre-mRNA sequences involved in splicing and blocking access to the transcript by splicing factors. Recently, the efficacy of SSOs has been established in various animal disease models; however, the application of SSOs against cancer targets has been hindered by poor in vivo delivery of antisense therapeutics to tumor cells. T...

  9. A PARALLEL SWITCH FABRIC BASED ON CROSSBAR

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    With the increase of link rate, the arbitrator of centralized switch fabric becomes too complicated to implement. A parallel switch fabric based on crossbar, named as PSFBC (Parallel Switch Fabric Based on Crossbar), has been proposed in this paper. PSFBC is composed of k switches whose rate is 1/k of link', these switches exchange cells in parallel; this increases the arbitrator's period and make it easy to implement. Load is evenly distributed to each switch with FCFS (First Come First Serve) rule, it can keep the order of cells in one stream. A multi-class queue scheduling policy is used in PSFBC to ensure the quality of realtime streams. Experiments show that the load on each switch in PSFBC is well balanced, its average delay of cells is little and its performance is very close to centralized switch; and with the increase of number of parallel switches, the loss of PSFBC's performance keeps very small, it becomes easier to implement.

  10. Critical dwell time of switched linear systems

    Institute of Scientific and Technical Information of China (English)

    Lijun ZHANG; Chunwen LI

    2006-01-01

    In this paper, we consider the relation between the switching dwell time and the stabilization of switched linear control systems. First of all, a concept of critical dwell time is given for switched linear systems without control inputs, and the critical dwell time is taken as an arbitrary given positive constant for a switched linear control systems with controllable switching models. Secondly, when a switched linear system has many stabilizable switching models, the problem of stabilization of the overall system is considered. An on-line feedback control is designed such that the overall system is asymptotically stabilizable under switching laws which depend only on those of uncontrollable subsystems of the switching models. Finally, when a switched system is partially controllable (While some switching models are probably unstabilizable), an on-line feedback control and a cyclic switching strategy are designed such that the overall system is asymptotically stabilizable if all switching models of this uncontrollable subsystems are asymptotically stable. In addition,algorithms for designing switching laws and controls are presented.

  11. 7 CFR 12.23 - Conservation plans and conservation systems.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Conservation plans and conservation systems. 12.23 Section 12.23 Agriculture Office of the Secretary of Agriculture HIGHLY ERODIBLE LAND AND WETLAND CONSERVATION Highly Erodible Land Conservation § 12.23 Conservation plans and conservation systems. (a) Use...

  12. Portable Userspace Virtual Filesystem Switch

    Directory of Open Access Journals (Sweden)

    Łukasz Faber

    2013-01-01

    Full Text Available Multiple different filesystems — including disk-based, network, distributed, abstract — arean integral part of every operating system. They are usually written as kernel modules and abstracted to the user via a virtual filesystem switch. In this paper we analyse the feasibility of reimplementing the virtual filesystem switch as a userspace daemon and applicability of this approach in real-life usage. Such reimplementation will require a way to virtualise processes behaviour related to filesystem operations. The problem is non-trivial, as we assume limited capabilities of the VFS switch implemented in userspace. We present a layered architecture comprising of a monitoring process, the VFS abstraction and real filesystem implementations. All working in userspace. Then, we evaluate this solution in four areas: portability, feasibility, usability and performance. Our results demonstrate possible gains in using the userspace-based approach with monolithic kernels, but also underline problems that are encountered in this approach.

  13. Thiol-based redox switches in prokaryotes.

    Science.gov (United States)

    Hillion, Melanie; Antelmann, Haike

    2015-05-01

    Bacteria encounter reactive oxygen species (ROS) as a consequence of the aerobic life or as an oxidative burst of activated neutrophils during infections. In addition, bacteria are exposed to other redox-active compounds, including hypochloric acid (HOCl) and reactive electrophilic species (RES) such as quinones and aldehydes. These reactive species often target the thiol groups of cysteines in proteins and lead to thiol-disulfide switches in redox-sensing regulators to activate specific detoxification pathways and to restore the redox balance. Here, we review bacterial thiol-based redox sensors that specifically sense ROS, RES and HOCl via thiol-based mechanisms and regulate gene transcription in Gram-positive model bacteria and in human pathogens, such as Staphylococcus aureus and Mycobacterium tuberculosis. We also pay particular attention to emerging widely conserved HOCl-specific redox regulators that have been recently characterized in Escherichia coli. Different mechanisms are used to sense and respond to ROS, RES and HOCl by 1-Cys-type and 2-Cys-type thiol-based redox sensors that include versatile thiol-disulfide switches (OxyR, OhrR, HypR, YodB, NemR, RclR, Spx, RsrA/RshA) or alternative Cys phosphorylations (SarZ, MgrA, SarA), thiol-S-alkylation (QsrR), His-oxidation (PerR) and methionine oxidation (HypT). In pathogenic bacteria, these redox-sensing regulators are often important virulence regulators and required for adapation to the host immune defense.

  14. Stochastic switching in biology: from genotype to phenotype

    Science.gov (United States)

    Bressloff, Paul C.

    2017-03-01

    There has been a resurgence of interest in non-equilibrium stochastic processes in recent years, driven in part by the observation that the number of molecules (genes, mRNA, proteins) involved in gene expression are often of order 1-1000. This means that deterministic mass-action kinetics tends to break down, and one needs to take into account the discrete, stochastic nature of biochemical reactions. One of the major consequences of molecular noise is the occurrence of stochastic biological switching at both the genotypic and phenotypic levels. For example, individual gene regulatory networks can switch between graded and binary responses, exhibit translational/transcriptional bursting, and support metastability (noise-induced switching between states that are stable in the deterministic limit). If random switching persists at the phenotypic level then this can confer certain advantages to cell populations growing in a changing environment, as exemplified by bacterial persistence in response to antibiotics. Gene expression at the single-cell level can also be regulated by changes in cell density at the population level, a process known as quorum sensing. In contrast to noise-driven phenotypic switching, the switching mechanism in quorum sensing is stimulus-driven and thus noise tends to have a detrimental effect. A common approach to modeling stochastic gene expression is to assume a large but finite system and to approximate the discrete processes by continuous processes using a system-size expansion. However, there is a growing need to have some familiarity with the theory of stochastic processes that goes beyond the standard topics of chemical master equations, the system-size expansion, Langevin equations and the Fokker-Planck equation. Examples include stochastic hybrid systems (piecewise deterministic Markov processes), large deviations and the Wentzel-Kramers-Brillouin (WKB) method, adiabatic reductions, and queuing/renewal theory. The major aim of this

  15. Finite-time quantised feedback asynchronously switched control of sampled-data switched linear systems

    Science.gov (United States)

    Wang, Ronghao; Xing, Jianchun; Li, Juelong; Xiang, Zhengrong

    2016-10-01

    This paper studies the problem of stabilising a sampled-data switched linear system by quantised feedback asynchronously switched controllers. The idea of a quantised feedback asynchronously switched control strategy originates in earlier work reflecting actual system characteristic of switching and quantising, respectively. A quantised scheme is designed depending on switching time using dynamic quantiser. When sampling time, system switching time and controller switching time are all not uniform, the proposed switching controllers guarantee the system to be finite-time stable by a piecewise Lyapunov function and the average dwell-time method. Simulation examples are provided to show the effectiveness of the developed results.

  16. Topology optimized RF MEMS switches

    DEFF Research Database (Denmark)

    Philippine, M. A.; Zareie, H.; Sigmund, Ole

    2013-01-01

    Topology optimization is a rigorous and powerful method that should become a standard MEMS design tool - it can produce unique and non-intuitive designs that meet complex objectives and can dramatically improve the performance and reliability of MEMS devices. We present successful uses of topology...... optimization for an RF MEM capacitive switch. Extensive experimental data confirms that the switches perform as designed by the optimizations, and that our simulation models are accurate. A subset of measurements are presented here. Broader results have been submitted in full journal format....

  17. CMOS integrated switching power converters

    CERN Document Server

    Villar-Pique, Gerard

    2011-01-01

    This book describes the structured design and optimization of efficient, energy processing integrated circuits. The approach is multidisciplinary, covering the monolithic integration of IC design techniques, power electronics and control theory. In particular, this book enables readers to conceive, synthesize, design and implement integrated circuits with high-density high-efficiency on-chip switching power regulators. Topics covered encompass the structured design of the on-chip power supply, efficiency optimization, IC-compatible power inductors and capacitors, power MOSFET switches and effi

  18. Long Life MEM Switch Technology

    Science.gov (United States)

    2006-05-23

    switched capacitors. It proves that by decreasing the size, miniature switched capacitors with Con/ Coff =2.8 for a single bridge and Con/ Coff =1.9 for a 3...TRANSACTIONS ON MICROWAVE THEORY AND TECHNIQUES, 2006 top covershielding housing fabricated filterb i a s p r o b e a p e r t u r e r e f e r e n c...e p l a n e s 2 m m Fig. 16. The fabricated filter in the shielding housing (cover removed). Frequency (GHz) 2 3 4 5 6 7 S -p a ra m e te rs ( d B

  19. STABILITY OF SWITCHED POLYNOMIAL SYSTEMS

    Institute of Scientific and Technical Information of China (English)

    Zhiqiang LI; Yupeng QIAO; Hongsheng QI; Daizhan CHENG

    2008-01-01

    This paper investigates the stability of (switched) polynomial systems. Using semi-tensor product of matrices, the paper develops two tools for testing the stability of a (switched) polynomial system. One is to convert a product of multi-variable polynomials into a canonical form, and the other is an easily verifiable sufficient condition to justify whether a multi-variable polynomial is positive definite. Using these two tools, the authors construct a polynomial function as a candidate Lyapunov function and via testing its derivative the authors provide some sufficient conditions for the global stability of polynomial systems.

  20. Switch Using Radio Frequency Identification

    Science.gov (United States)

    Fink, Patrick W. (Inventor); Lin, Gregory Y. (Inventor); Kennedy, Timothy F. (Inventor); Ngo, Phong H. (Inventor)

    2015-01-01

    Disclosed is an apparatus for use as a switch. In one embodiment, the switch comprises at least one RFID tag, each RFID tag comprising an antenna element and an RFID integrated circuit, at least one source element, and at least one lever arm. Each lever arm is connected to one of the RFID tags, and each lever arm is capable of two positions. One of the positions places the lever arm and the RFID tag connected thereto into alignment with the source element. Other embodiments are also described.

  1. Conservation: Toward firmer ground

    Science.gov (United States)

    1975-01-01

    The following aspects of energy conservation were discussed: conservation history and goals, conservation modes, conservation accounting-criteria, and a method to overcome obstacles. The conservation modes tested fall into one of the following categories: reduced energy consumption, increased efficiency of energy utilization, or substitution of one or more forms of energy for another which is in shorter supply or in some sense thought to be of more value. The conservation accounting criteria include net energy reduction, economic, and technical criteria. A method to overcome obstacles includes (approaches such as: direct personal impact (life style, income, security, aspiration), an element of crisis, large scale involvement of environmental, safety, and health issues, connections to big government, big business, big politics, involvement of known and speculative science and technology, appeal to moral and ethical standards, the transient nature of opportunities to correct the system.

  2. Bumpless switching control for switched systems with partial actuator failures

    Science.gov (United States)

    Qi, Yiwen; Bao, Wen; Zhang, Qingxin; Chang, Juntao

    2016-11-01

    This study is concerned with the bumpless transfer problem for switched systems with partial actuator failures, in order to obtain smooth system performance output transition. Taking into account that the system requires a controller switching from current sub-controller to a fault-tolerant sub-controller after actuator fault. And bumpless transfer for control input cannot be traditionally designed when the actuator fault occurs, while performance smoothing can be considered and it is actually the ultimate goal of bumpless transfer. Specifically, the actuator fault model is firstly established and partial actuator fault is considered. Then, the system performance output signal is deemed as the main design variable of bumpless transfer, and closed-loop control systems both previous and after controller switching are constructed. Moreover, by using model matching thought and the adaptive sliding mode control technique, a bumpless transfer compensator design strategy is given to drive the performance output variable (after controller switching) to track the one of reference model. At last, simulation results of numeric and application examples demonstrate the effectiveness of the proposed bumpless transfer strategy.

  3. Switching in electrical transmission and distribution systems

    CERN Document Server

    Smeets, René; Kapetanovic, Mirsad; Peelo, David F; Janssen, Anton

    2014-01-01

    Switching in Electrical Transmission and Distribution Systems presents the issues and technological solutions associated with switching in power systems, from medium to ultra-high voltage. The book systematically discusses the electrical aspects of switching, details the way load and fault currents are interrupted, the impact of fault currents, and compares switching equipment in particular circuit-breakers. The authors also explain all examples of practical switching phenomena by examining real measurements from switching tests. Other highlights include: up to date commentary on new develo

  4. EMT and MET as paradigms for cell fate switching

    Institute of Scientific and Technical Information of China (English)

    Jiekai Chen; Qingkai Han; Duanqing Pei

    2012-01-01

    Cell fate determination is a major unsolved problem in cell and developmental biology,The discovery of reprogramming by pluripotent factors offers a rational system to investigate the molecular mechanisms associated with cell fate decisions.The idea that reprogramming of fibroblasts starts with a mesenchymal-epithelial transition (MET) suggests that the process is perhaps a reversal of epithelial to mesenchymal transition (EMT) found frequently during early embryogenesis,As such,we believe that investigations into MET-EMT may yield detailed molecular insights into cell fate decisions,not only for the switching between epithelial and mesenchymal cells,but also other cell types.

  5. Hybrid colored noise process with space-dependent switching rates

    Science.gov (United States)

    Bressloff, Paul C.; Lawley, Sean D.

    2017-07-01

    A fundamental issue in the theory of continuous stochastic process is the interpretation of multiplicative white noise, which is often referred to as the Itô-Stratonovich dilemma. From a physical perspective, this reflects the need to introduce additional constraints in order to specify the nature of the noise, whereas from a mathematical perspective it reflects an ambiguity in the formulation of stochastic differential equations (SDEs). Recently, we have identified a mechanism for obtaining an Itô SDE based on a form of temporal disorder. Motivated by switching processes in molecular biology, we considered a Brownian particle that randomly switches between two distinct conformational states with different diffusivities. In each state, the particle undergoes normal diffusion (additive noise) so there is no ambiguity in the interpretation of the noise. However, if the switching rates depend on position, then in the fast switching limit one obtains Brownian motion with a space-dependent diffusivity of the Itô form. In this paper, we extend our theory to include colored additive noise. We show that the nature of the effective multiplicative noise process obtained by taking both the white-noise limit (κ →0 ) and fast switching limit (ɛ →0 ) depends on the order the two limits are taken. If the white-noise limit is taken first, then we obtain Itô, and if the fast switching limit is taken first, then we obtain Stratonovich. Moreover, the form of the effective diffusion coefficient differs in the two cases. The latter result holds even in the case of space-independent transition rates, where one obtains additive noise processes with different diffusion coefficients. Finally, we show that yet another form of multiplicative noise is obtained in the simultaneous limit ɛ ,κ →0 with ɛ /κ2 fixed.

  6. High On/Off Conductance Switching Ratio via H-Tautomerization in Quinone.

    Science.gov (United States)

    Tawfik, Sherif Abdulkader; Cui, X Y; Ringer, S P; Stampfl, C

    2015-09-01

    Through first-principles electron transport simulations using the nonequilibrium Green's function formalism together with density functional theory, we show that, upon H-tautomerization, a simple derivative of quinone can act as a molecular switch with high ON/OFF ratio, up to 70 at low bias voltage. This switching behavior is explained by the quantum interference effect, where the positional change of hydrogen atoms causes the energies of the transmission channels to overlap. Our results suggest that this molecule could have potential applications as an effective switching device.

  7. Controlled switching of single-molecule junctions by mechanical motion of a phenyl ring

    Directory of Open Access Journals (Sweden)

    Yuya Kitaguchi

    2015-10-01

    Full Text Available Mechanical methods for single-molecule control have potential for wide application in nanodevices and machines. Here we demonstrate the operation of a single-molecule switch made functional by the motion of a phenyl ring, analogous to the lever in a conventional toggle switch. The switch can be actuated by dual triggers, either by a voltage pulse or by displacement of the electrode, and electronic manipulation of the ring by chemical substitution enables rational control of the on-state conductance. Owing to its simple mechanics, structural robustness, and chemical accessibility, we propose that phenyl rings are promising components in mechanical molecular devices.

  8. Paradigms for parasite conservation.

    Science.gov (United States)

    Dougherty, Eric R; Carlson, Colin J; Bueno, Veronica M; Burgio, Kevin R; Cizauskas, Carrie A; Clements, Christopher F; Seidel, Dana P; Harris, Nyeema C

    2016-08-01

    Parasitic species, which depend directly on host species for their survival, represent a major regulatory force in ecosystems and a significant component of Earth's biodiversity. Yet the negative impacts of parasites observed at the host level have motivated a conservation paradigm of eradication, moving us farther from attainment of taxonomically unbiased conservation goals. Despite a growing body of literature highlighting the importance of parasite-inclusive conservation, most parasite species remain understudied, underfunded, and underappreciated. We argue the protection of parasitic biodiversity requires a paradigm shift in the perception and valuation of their role as consumer species, similar to that of apex predators in the mid-20th century. Beyond recognizing parasites as vital trophic regulators, existing tools available to conservation practitioners should explicitly account for the unique threats facing dependent species. We built upon concepts from epidemiology and economics (e.g., host-density threshold and cost-benefit analysis) to devise novel metrics of margin of error and minimum investment for parasite conservation. We define margin of error as the risk of accidental host extinction from misestimating equilibrium population sizes and predicted oscillations, while minimum investment represents the cost associated with conserving the additional hosts required to maintain viable parasite populations. This framework will aid in the identification of readily conserved parasites that present minimal health risks. To establish parasite conservation, we propose an extension of population viability analysis for host-parasite assemblages to assess extinction risk. In the direst cases, ex situ breeding programs for parasites should be evaluated to maximize success without undermining host protection. Though parasitic species pose a considerable conservation challenge, adaptations to conservation tools will help protect parasite biodiversity in the face of

  9. Multiuser switched diversity scheduling schemes

    KAUST Repository

    Shaqfeh, Mohammad

    2012-09-01

    Multiuser switched-diversity scheduling schemes were recently proposed in order to overcome the heavy feedback requirements of conventional opportunistic scheduling schemes by applying a threshold-based, distributed, and ordered scheduling mechanism. The main idea behind these schemes is that slight reduction in the prospected multiuser diversity gains is an acceptable trade-off for great savings in terms of required channel-state-information feedback messages. In this work, we characterize the achievable rate region of multiuser switched diversity systems and compare it with the rate region of full feedback multiuser diversity systems. We propose also a novel proportional fair multiuser switched-based scheduling scheme and we demonstrate that it can be optimized using a practical and distributed method to obtain the feedback thresholds. We finally demonstrate by numerical examples that switched-diversity scheduling schemes operate within 0.3 bits/sec/Hz from the ultimate network capacity of full feedback systems in Rayleigh fading conditions. © 2012 IEEE.

  10. Magnetically Insulated Opening Switch Research.

    Science.gov (United States)

    1987-01-01

    this research is to investigate the validity of the magneti- cally insulated opening switch concept proposed by Eninger (Ref. 5, Appendix 1). The...1973). 3. Y. Carmel, and J. Nation, Phys, Rev. Lett. 31, 286 (1973). 4. T.J. Orzechowski, and G. Bekefi, Phys. Fluids 19, 43 (1976). U 5. 3. Eninger

  11. The Atlas load protection switch

    CERN Document Server

    Davis, H A; Dorr, G; Martínez, M; Gribble, R F; Nielsen, K E; Pierce, D; Parsons, W M

    1999-01-01

    Atlas is a high-energy pulsed-power facility under development to study materials properties and hydrodynamics experiments under extreme conditions. Atlas will implode heavy liner loads (m~45 gm) with a peak current of 27-32 MA delivered in 4 mu s, and is energized by 96, 240 kV Marx generators storing a total of 23 MJ. A key design requirement for Atlas is obtaining useful data for 95601130f all loads installed on the machine. Materials response calculations show current from a prefire can damage the load requiring expensive and time consuming replacement. Therefore, we have incorporated a set of fast-acting mechanical switches in the Atlas design to reduce the probability of a prefire damaging the load. These switches, referred to as the load protection switches, short the load through a very low inductance path during system charge. Once the capacitors have reached full charge, the switches open on a time scale short compared to the bank charge time, allowing current to flow to the load when the trigger pu...

  12. Industry Switching in Developing Countries

    DEFF Research Database (Denmark)

    Newman, Carol; Rand, John; Tarp, Finn

    as compared to entry and exit firms. They tend, inter alia, to be labour-intensive and seek out competitive opportunities in labour-intensive sectors in response to changes in the market environment. We also show that resource reallocations resulting from switching form an important component of productivity...

  13. Wide Bandgap Extrinsic Photoconductive Switches

    Energy Technology Data Exchange (ETDEWEB)

    Sullivan, James S. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2013-07-03

    Semi-insulating Gallium Nitride, 4H and 6H Silicon Carbide are attractive materials for compact, high voltage, extrinsic, photoconductive switches due to their wide bandgap, high dark resistance, high critical electric field strength and high electron saturation velocity. These wide bandgap semiconductors are made semi-insulating by the addition of vanadium (4H and 6HSiC) and iron (2H-GaN) impurities that form deep acceptors. These deep acceptors trap electrons donated from shallow donor impurities. The electrons can be optically excited from these deep acceptor levels into the conduction band to transition the wide bandgap semiconductor materials from a semi-insulating to a conducting state. Extrinsic photoconductive switches with opposing electrodes have been constructed using vanadium compensated 6H-SiC and iron compensated 2H-GaN. These extrinsic photoconductive switches were tested at high voltage and high power to determine if they could be successfully used as the closing switch in compact medical accelerators.

  14. Switching Costs in Accounting Services

    Directory of Open Access Journals (Sweden)

    Fatih Koç

    2015-06-01

    Full Text Available Switching cost is defined as possible costs that customers may encounter when they want to change the firm they buy service, and an important subject in terms of accounting services. Particularly, small business entrepreneurs’ not having knowledge about accounting procedures, and sharing private information with accounting firms make switching costs more important for accounting services. Thus, the aim of this study is to investigate the concept of switching costs (relational cost, procedural cost and financial cost, its determinants (perceived service quality, service importance, and service failures, and consequences (re-purchasing, and recommen ding to others. Theresearch was conducted on small business entrepreneurs in down-town of Balıkesir in Turkey. Total 405 small business entrepreneur owners were interviewed. According to results of the study, perceived service quality positively affects all dimensions of switching costs, significance of service positively affects procedural and relational costs, and service failures negatively affect procedural and relational costs. The results showed that while procedural and relational costs positively affect re-purchasing and recommending to others variables, financial cost did not have any effect on these variables.

  15. Intrinsic nanofilamentation in resistive switching

    KAUST Repository

    Wu, Xing

    2013-03-15

    Resistive switching materials are promising candidates for nonvolatile data storage and reconfiguration of electronic applications. Intensive studies have been carried out on sandwiched metal-insulator-metal structures to achieve high density on-chip circuitry and non-volatile memory storage. Here, we provide insight into the mechanisms that govern highly reproducible controlled resistive switching via a nanofilament by using an asymmetric metal-insulator-semiconductor structure. In-situ transmission electron microscopy is used to study in real-time the physical structure and analyze the chemical composition of the nanofilament dynamically during resistive switching. Electrical stressing using an external voltage was applied by a tungsten tip to the nanosized devices having hafnium oxide (HfO2) as the insulator layer. The formation and rupture of the nanofilaments result in up to three orders of magnitude change in the current flowing through the dielectric during the switching event. Oxygen vacancies and metal atoms from the anode constitute the chemistry of the nanofilament.

  16. Industry Switching in Developing Countries

    DEFF Research Database (Denmark)

    Newman, Carol; Rand, John; Tarp, Finn

    Firm turnover (i.e. firm entry and exit) is a well-recognized source of sectorlevel productivity growth across developing and developed countries. In contrast, the role and importance of firms switching activities from one sector to another is little understood. Firm switchers are likely to be un...

  17. CSR Pulsed Switching Power Supplies

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    In 2001, CSR power supply system made a great progress. Three prototypes were designed for CSR quadruple and correct magnet. Three different companies provided the three prototypes, but the same circuit-chopper were employed. The simplified diagram is showed in Fig.1. All pulsed switching power supply prototypes were tested successfully before the end of 2001.

  18. Soliton switching in directional couplers

    NARCIS (Netherlands)

    Valkering, T.P.; Hoekstra, Hugo; de Boer, Pieter-Tjerk

    1999-01-01

    The mechanism of pulse switching is investigated analytically and numerically for a family of initial conditions with a solitonlike pulse in one channel and no signal on the other channel of the coupler. This investigation is performed directly in the coupled nonlinear Schroedinger equations that

  19. Digital Switching in the Quantum Domain

    CERN Document Server

    Tsai, I M

    2002-01-01

    In this paper, we present an architecture and implementation algorithm such that digital data can be switched in the quantum domain. First we define the connection digraph which can be used to describe the behavior of a switch at a given time, then we show how a connection digraph can be implemented using elementary quantum gates. The proposed mechanism supports unicasting as well as multicasting, and is strict-sense non-blocking. It can be applied to perform either circuit switching or packet switching. Compared with a traditional space or time domain switch, the proposed switching mechanism is more scalable. Assuming an n-by-n quantum switch, the space consumption grows linearly, i.e. O(n), while the time complexity is O(1) for unicasting, and O(log n) for multicasting. Based on these advantages, a high throughput switching device can be built simply by increasing the number of I/O ports.

  20. Key Technologies for Optical Packet Switching

    Institute of Scientific and Technical Information of China (English)

    Akira; Okada

    2003-01-01

    The paper describes our recent progress on key technologies and components for realizing optical packet switching, including an out-of-band optical label switching technique, an optical packet synchronizer and a burst-mode optical receiver.