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Sample records for array finely tuned

  1. Fine-Tuning Corrective Feedback.

    ERIC Educational Resources Information Center

    Han, ZhaoHong

    2001-01-01

    Explores the notion of "fine-tuning" in connection with the corrective feedback process. Describes a longitudinal case study, conducted in the context of Norwegian as a second a language, that shows how fine-tuning and lack thereof in the provision of written corrective feedback differentially affects a second language learner's restructuring of…

  2. Automated Camera Array Fine Calibration

    NASA Technical Reports Server (NTRS)

    Clouse, Daniel; Padgett, Curtis; Ansar, Adnan; Cheng, Yang

    2008-01-01

    Using aerial imagery, the JPL FineCalibration (JPL FineCal) software automatically tunes a set of existing CAHVOR camera models for an array of cameras. The software finds matching features in the overlap region between images from adjacent cameras, and uses these features to refine the camera models. It is not necessary to take special imagery of a known target and no surveying is required. JPL FineCal was developed for use with an aerial, persistent surveillance platform.

  3. Understanding the Fine Tuning in Our Universe

    ERIC Educational Resources Information Center

    Cohen, Bernard L.

    2008-01-01

    It is often stated that the physical properties of our universe are "fine tuned"--that is, they must be almost exactly as they are to make the development of intelligent life possible. The implications of this statement, called the "anthropic principle," have been widely discussed in a philosophical context, but the scientific basis for the…

  4. Resistive Fine Tuning of Resonant Circuit

    NASA Technical Reports Server (NTRS)

    Mclyman, C. W.

    1985-01-01

    Simple fixed-inductance/fixed-capacitance tank circuit modified for fine adjustment of resonant frequency by addition of small inductance with potentiometer across it. Additional winding built into full winding as integral part or added externally. Technique provides quick way of tuning reactance out of power-transformer circuit to maximize power transfer or to adjust frequency of oscillator. Applications include rotary transformers, servo amplifiers, and analog computer modules.

  5. A cyclic universe approach to fine tuning

    NASA Astrophysics Data System (ADS)

    Alexander, Stephon; Cormack, Sam; Gleiser, Marcelo

    2016-06-01

    We present a closed bouncing universe model where the value of coupling constants is set by the dynamics of a ghost-like dilatonic scalar field. We show that adding a periodic potential for the scalar field leads to a cyclic Friedmann universe where the values of the couplings vary randomly from one cycle to the next. While the shuffling of values for the couplings happens during the bounce, within each cycle their time-dependence remains safely within present observational bounds for physically-motivated values of the model parameters. Our model presents an alternative to solutions of the fine tuning problem based on string landscape scenarios.

  6. Pre - big bang inflation requires fine tuning

    SciTech Connect

    Turner, Michael S.; Weinberg, Erick J.

    1997-10-01

    The pre-big-bang cosmology inspired by superstring theories has been suggested as an alternative to slow-roll inflation. We analyze, in both the Jordan and Einstein frames, the effect of spatial curvature on this scenario and show that too much curvature --- of either sign --- reduces the duration of the inflationary era to such an extent that the flatness and horizon problems are not solved. Hence, a fine-tuning of initial conditions is required to obtain enough inflation to solve the cosmological problems.

  7. Transcriptional coregulators: fine-tuning metabolism

    PubMed Central

    Mouchiroud, Laurent; Eichner, Lillian J.; Shaw, Reuben; Auwerx, Johan

    2014-01-01

    Metabolic homeostasis requires that cellular energy levels are adapted to environmental cues. This adaptation is largely regulated at the transcriptional level, through the interaction between transcription factors, coregulators, and the basal transcriptional machinery. Coregulators, which function both as metabolic sensors and transcriptional effectors, are ideally positioned to synchronize metabolic pathways to environmental stimuli. The balance between inhibitory actions of corepressors and stimulatory effects of coactivators enables the fine-tuning of metabolic processes. The tight regulation opens therapeutic opportunities to manage metabolic dysfunction, by directing the activity of cofactors towards specific transcription factors, pathways, or cells/tissues, thereby restoring whole body metabolic homeostasis. PMID:24794975

  8. Rig designers continue fine-tuning

    SciTech Connect

    Pagano, S.S.

    1993-04-01

    Rig designers and owners continue to fine-tune a variety of sophisticated new generation semisubmersible and jackup designs that will go into production once supply catches up with demand, later in the decade. The units will be designed to meet the latest international safety requirements, be more highly specialized that most existing rigs, and they will be expensive. Rising oil prices and improved rig utilization will be the catalysts to spur future rig orders. Over the longer term, the aging semi fleet will need to be upgraded or replaced beginning in the second half of the deacade. Rig life extension programs will be economically justified for many rigs, but new construction will pay a significant role in the semi fleet this decade. Many rig designs will be capable of ultra-deep-water drilling and production in water depths as deep as 10,000 feet. Additional designs concepts and projects are discussed.

  9. Fine tuning of cytosolic Ca 2+ oscillations

    PubMed Central

    Dupont, Geneviève; Combettes, Laurent

    2016-01-01

    Ca 2+ oscillations, a widespread mode of cell signaling, were reported in non-excitable cells for the first time more than 25 years ago. Their fundamental mechanism, based on the periodic Ca 2+ exchange between the endoplasmic reticulum and the cytoplasm, has been well characterized. However, how the kinetics of cytosolic Ca 2+ changes are related to the extent of a physiological response remains poorly understood. Here, we review data suggesting that the downstream targets of Ca 2+ are controlled not only by the frequency of Ca 2+ oscillations but also by the detailed characteristics of the oscillations, such as their duration, shape, or baseline level. Involvement of non-endoplasmic reticulum Ca 2+ stores, mainly mitochondria and the extracellular medium, participates in this fine tuning of Ca 2+ oscillations. The main characteristics of the Ca 2+ exchange fluxes with these compartments are also reviewed.

  10. Understanding the Fine Tuning in Our Universe

    NASA Astrophysics Data System (ADS)

    Cohen, Bernard L.

    2008-05-01

    I It is often stated that the physical properties of our universe are ``fine tuned''-that is, they must be almost exactly as they are to make the development of intelligent life possible.1 The implications of this statement, called the ``anthropic principle,'' have been widely discussed in a philosophical context,2 but the scientific basis for the statement3 is not widely understood outside the community of experts. My purpose here is to explain how I have presented some parts of this scientific basis, albeit with some glossing over of difficult and/or less important details, to undergraduate students majoring in humanities and social sciences and to senior citizens in ``lifetime learning'' programs who have no professional scientific background. In this paper, I concentrate on the vital processes of hydrogen burning and helium burning.

  11. A Local Contingency Analysis of the Fine-Tuning Hypothesis.

    ERIC Educational Resources Information Center

    Sokolov, Jeffrey L.

    1993-01-01

    Tested the fine-tuning hypothesis of language acquisition, which postulates that parents fine-tune their speech to their children's language level, by examining local patterns of interaction within the conversations of three parent-child dyads. The high positive correlations between parent-child dyads for the different interactional patterns…

  12. Approaching {lambda} without fine-tuning

    SciTech Connect

    Matarrese, Sabino; Baccigalupi, Carlo; Perrotta, Francesca

    2004-09-15

    We address the fine-tuning problem of dark energy cosmologies which arises when the dark energy density needs to initially lie in a narrow range in order for its present value to be consistent with observations. As recently noticed, this problem becomes particularly severe in canonical quintessence scenarios, when trying to reproduce the behavior of a cosmological constant, i.e., when the dark energy equation of state w{sub Q} approaches -1: these models may be reconciled with a large basin of attraction only by requiring a rapid evolution of w{sub Q} at low redshifts, which is in conflict with the most recent estimates from type Ia Supernovae discovered by Hubble space telescope. Next, we focus on scalar-tensor theories of gravity, discussing the implications of a coupling between the quintessence scalar field and the Ricci scalar ('extended quintessence'). We show that, even if the equation of state today is very close to -1, by virtue of the scalar-tensor coupling the quintessence trajectories still possess the attractive feature which allows to reach the present level of cosmic acceleration starting by a set of initial conditions which covers tens of orders of magnitude; this effect, entirely of gravitational origin, represents a new important consequence of the possible coupling between dark energy and gravity. We illustrate this effect in typical extended quintessence scenarios.

  13. The Fine-Tuning of Nomic Behavior in Multiverse Scenarios

    NASA Astrophysics Data System (ADS)

    Andrews, Max Lewis Edward

    The multiverse hypothesis (the view that there is not just one world or universe in existence, bur rather that there are many) is the leading alternative to the competing fine-tuning hypothesis (the laws of physics and constants are fine-tuned for the existence of life). The multiverse dispels many aspects of the fine-tuning argument by suggesting that there are different initial conditions in each universe, varying constants of physics, and the laws of nature lose their known arbitrary values; thus, making the previous single-universe argument from fine- tuning incredibly weak. The position that will be advocated will be that a form of multiverse could exist and that any level of Tegmark's multiverse does not circumvent the fine-tuning argument for the existence of a fine-tuner (a mind). An argument will be presented suggesting that the multiverse could strengthen the fine-tuning argument by narrowing down the parameters of the data to a more fundamental description needed for the multiverse to function as it does since it may be the case that some physical descriptions are not the same in every universe. That is, the task of explaining how the multiverse mechanism functions cannot be accounted for by the multiverse itself. Fine-tuning by a mind serves as a sufficient and best explanation for the data.

  14. The apparent fine-tuning of the cosmological, gravitational and fine structure constants

    NASA Astrophysics Data System (ADS)

    Eaves, Laurence

    2016-02-01

    A numerical coincidence relating the values of the cosmological, gravitational and electromagnetic fine structure constants is presented and discussed in relation to the apparent anthropic fine-tuning of these three fundamental constants of nature.

  15. Fine-Tuning Your Ensemble's Jazz Style.

    ERIC Educational Resources Information Center

    Garcia, Antonio J.

    1991-01-01

    Proposes instructional strategies for directors of jazz groups, including guidelines for developing of skills necessary for good performance. Includes effective methods for positive changes in ensemble style. Addresses jazz group problems such as beat, tempo, staying in tune, wind power, and solo/ensemble lines. Discusses percussionists, bassists,…

  16. On the MSSM Higgsino mass and fine tuning

    NASA Astrophysics Data System (ADS)

    Ross, Graham G.; Schmidt-Hoberg, Kai; Staub, Florian

    2016-08-01

    It is often argued that low fine tuning in the MSSM necessarily requires a rather light Higgsino. In this note we show that this need not be the case when a more complete set of soft SUSY breaking mass terms are included. In particular an Higgsino mass term, that correlates the μ-term contribution with the soft SUSY-breaking Higgsino masses, significantly reduces the fine tuning even for Higgsinos in the TeV mass range where its relic abundance means it can make up all the dark matter.

  17. Fine-Tuning and the Stability of Recurrent Neural Networks

    PubMed Central

    MacNeil, David; Eliasmith, Chris

    2011-01-01

    A central criticism of standard theoretical approaches to constructing stable, recurrent model networks is that the synaptic connection weights need to be finely-tuned. This criticism is severe because proposed rules for learning these weights have been shown to have various limitations to their biological plausibility. Hence it is unlikely that such rules are used to continuously fine-tune the network in vivo. We describe a learning rule that is able to tune synaptic weights in a biologically plausible manner. We demonstrate and test this rule in the context of the oculomotor integrator, showing that only known neural signals are needed to tune the weights. We demonstrate that the rule appropriately accounts for a wide variety of experimental results, and is robust under several kinds of perturbation. Furthermore, we show that the rule is able to achieve stability as good as or better than that provided by the linearly optimal weights often used in recurrent models of the integrator. Finally, we discuss how this rule can be generalized to tune a wide variety of recurrent attractor networks, such as those found in head direction and path integration systems, suggesting that it may be used to tune a wide variety of stable neural systems. PMID:21980334

  18. Why Cosmic Fine-Tuning Needs to BE Explained

    NASA Astrophysics Data System (ADS)

    Manson, Neil Alan

    Discoveries in modern physics and Big Bang cosmology indicate that if either the initial conditions of the universe or the physical laws governing its development had differed even slightly, life could never have developed. It is for this reason that the universe is said to be ``fine-tuned'' for life. I argue that cosmic fine-tuning, which some want to dismiss as the way things just happen to be, in fact needs to be explained. In Chapter One I provide an overview of the evidence that the universe is fine-tuned for life. In Chapter Two I present a set of sufficient conditions for a fact's needing to be explained. The conditions are that the fact is improbable and that a ``tidy'' explanation of it is available. A tidy explanation of a fact is considerably less improbable than that fact and makes the obtaining of that fact considerably less improbable. Chapters Three, Four, and Five are devoted to showing that cosmic Chapter Three I argue that the universe's being finely tuned for life can meaningfully be considered improbable. In Chapter Four I claim that there is at least one tidy explanation of cosmic fine-tuning: that the universe was created by some sort of extramundane designer. In Chapters Four and Five I respond to three objections. The first is that the design hypothesis is ad hoc. The second is that we have no reason to believe a supernatural designer would prefer life-permitting cosmoi to other possible cosmoi and that our tendency to believe otherwise is the result of anthropocentrism. The third is that the design hypothesis never buys us an explanatory advantage.

  19. Cosmologically Safe QCD Axion without Fine-Tuning

    NASA Astrophysics Data System (ADS)

    Yamada, Masaki; Yanagida, Tsutomu T.; Yonekura, Kazuya

    2016-02-01

    Although QCD axion models are widely studied as solutions to the strong C P problem, they generically confront severe fine-tuning problems to guarantee the anomalous Peccei-Quinn (PQ) symmetry. In this Letter, we propose a simple QCD axion model without any fine-tunings. We introduce an extra dimension and a pair of extra quarks living on two branes separately, which is also charged under a bulk Abelian gauge symmetry. We assume a monopole condensation on our brane at an intermediate scale, which implies that the extra quarks develop chiral symmetry breaking and the PQ symmetry is broken. In contrast to Kim's original model, our model explains the origin of the PQ symmetry thanks to the extra dimension and avoids the cosmological domain wall problem because of chiral symmetry breaking in Abelian gauge theory.

  20. Cosmologically Safe QCD Axion without Fine-Tuning.

    PubMed

    Yamada, Masaki; Yanagida, Tsutomu T; Yonekura, Kazuya

    2016-02-01

    Although QCD axion models are widely studied as solutions to the strong CP problem, they generically confront severe fine-tuning problems to guarantee the anomalous Peccei-Quinn (PQ) symmetry. In this Letter, we propose a simple QCD axion model without any fine-tunings. We introduce an extra dimension and a pair of extra quarks living on two branes separately, which is also charged under a bulk Abelian gauge symmetry. We assume a monopole condensation on our brane at an intermediate scale, which implies that the extra quarks develop chiral symmetry breaking and the PQ symmetry is broken. In contrast to Kim's original model, our model explains the origin of the PQ symmetry thanks to the extra dimension and avoids the cosmological domain wall problem because of chiral symmetry breaking in Abelian gauge theory. PMID:26894701

  1. Phased waveguide array with fixed tuning elements

    SciTech Connect

    Motley, R.W.; Bernabei, S.; Hooke, W.M.; Paoloni, F.J.

    1980-04-01

    The waveguide grill excites both penetrating lower hybrid waves and surface plasma waves. Quarter wavelength tuning elements attached to the sides of a twin waveguide are shown to reduce the surface wave component by a factor of approx. 3..

  2. Phase lock acquisition system having FLL for coarse tuning and PLL for fine tuning

    NASA Astrophysics Data System (ADS)

    Caldwell, S. P.; Decker, M. J.; Jelen, R. A.

    1986-04-01

    The acquisition of phase lock to a reference frequency by a signal acquisition system is accomplished using a voltage controlled oscillator, a wideband frequency discriminator, a prepositioning circuit, and a phase lock loop. The voltage controlled oscillator is prepositioned within a loop bandwidth of the reference frequency by the prepositioning circuit and the wide band frequency discriminator which provide coarse tuning. The voltage controlled oscillator achieves phase lock with the reference frequency when it receives the fine tune signal from the phase lock loop. Using both the discriminator and the phase lock loop allows fast acquisition without the need to calibrate the voltage controlled oscillator. Since the discriminator pull-in range is much larger than the phase-lock loop bandwidth, the number of bits can be much smaller than in acquisition circuit using a digital prepositioning circuit alone.

  3. Competitive binding of antagonistic peptides fine-tunes stomatal patterning

    PubMed Central

    Lee, Jin Suk; Hnilova, Marketa; Maes, Michal; Lin, Ya-Chen Lisa; Putarjunan, Aarthi; Han, Soon-Ki; Avila, Julian; U.Torii, Keiko

    2015-01-01

    During development, cells interpret complex, often conflicting signals to make optimal decisions. Plant stomata, the cellular interface between a plant and the atmosphere, develop according to positional cues including a family of secreted peptides, EPIDERMAL PATTERNING FACTORS (EPFs). How these signaling peptides orchestrate pattern formation at a molecular level remains unclear. Here we report that Stomagen/EPF-LIKE9 peptide, which promotes stomatal development, requires ERECTA (ER)-family receptor kinases and interferes with the inhibition of stomatal development by the EPF2-ER module. Both EPF2 and Stomagen directly bind to ER and its co-receptor TOO MANY MOUTHS. Stomagen peptide competitively replaced EPF2 binding to ER. Furthermore, application of EPF2, but not Stomagen, elicited rapid phosphorylation of downstream signaling components in vivo. Our findings demonstrate how a plant receptor agonist and antagonist define inhibitory and inductive cues to fine-tune tissue patterning on the plant epidermis. PMID:26083750

  4. Polar opposites: fine-tuning cytokinesis through SIN asymmetry

    PubMed Central

    Johnson, Alyssa E.; McCollum, Dannel; Gould, Kathleen L.

    2012-01-01

    Mitotic exit and cell division must be spatially and temporally integrated to facilitate equal division of genetic material between daughter cells. In the fission yeast, Schizosaccharomyces pombe, a spindle pole body (SPB) localized signaling cascade termed the septation initiation network (SIN) couples mitotic exit with cytokinesis. The SIN is controlled at many levels to ensure that cytokinesis is executed once per cell cycle and only after cells segregate their DNA. An interesting facet of the SIN is that its activity is asymmetric on the two SPBs during anaphase; however, how and why the SIN is asymmetric has remained elusive. Many key factors controlling SIN asymmetry have now been identified, shedding light on the significance of SIN asymmetry in regulating cytokinesis. In this review, we highlight recent advances in our understanding of SIN regulation, with an emphasis on how SIN asymmetry is achieved and how this aspect of SIN regulation fine-tunes cytokinesis. PMID:22786806

  5. Fine-tuning tomato agronomic properties by computational genome redesign.

    PubMed

    Carrera, Javier; Fernández Del Carmen, Asun; Fernández-Muñoz, Rafael; Rambla, Jose Luis; Pons, Clara; Jaramillo, Alfonso; Elena, Santiago F; Granell, Antonio

    2012-01-01

    Considering cells as biofactories, we aimed to optimize its internal processes by using the same engineering principles that large industries are implementing nowadays: lean manufacturing. We have applied reverse engineering computational methods to transcriptomic, metabolomic and phenomic data obtained from a collection of tomato recombinant inbreed lines to formulate a kinetic and constraint-based model that efficiently describes the cellular metabolism from expression of a minimal core of genes. Based on predicted metabolic profiles, a close association with agronomic and organoleptic properties of the ripe fruit was revealed with high statistical confidence. Inspired in a synthetic biology approach, the model was used for exploring the landscape of all possible local transcriptional changes with the aim of engineering tomato fruits with fine-tuned biotechnological properties. The method was validated by the ability of the proposed genomes, engineered for modified desired agronomic traits, to recapitulate experimental correlations between associated metabolites. PMID:22685389

  6. Relaxion cosmology and the price of fine-tuning

    NASA Astrophysics Data System (ADS)

    Di Chiara, Stefano; Kannike, Kristjan; Marzola, Luca; Racioppi, Antonio; Raidal, Martti; Spethmann, Christian

    2016-05-01

    The relaxion scenario presents an intriguing extension of the standard model in which the particle introduced to solve to the strong C P problem, the axion, also achieves the dynamical relaxation of the Higgs boson mass term. In this work we complete this framework by proposing a scenario of inflationary cosmology that is consistent with all the observational constraints: the relaxion hybrid inflation with an asymmetric waterfall. In our scheme, the vacuum energy of the inflaton drives inflation in a natural way while the relaxion slow rolls. The constraints on the present inflationary observables are then matched through a subsequent inflationary epoch driven by the inflaton. We quantify the amount of fine-tuning of the proposed inflation scenario, concluding that the inflaton sector severely decreases the naturalness of the theory.

  7. Fine tuning points of generating function construction for linear recursions

    NASA Astrophysics Data System (ADS)

    Yolcu, Bahar; Demiralp, Metin

    2014-10-01

    Recursions are quite important mathematical tools since many systems are mathematically modelled to ultimately take us to these equations because of their rather easy algebraic natures. They fit computer programming needs quite well in many circumstances to produce solutions. However, it is generally desired to find the asymptotic behaviour of the general term in the relevant sequence for convergence and therefore practicality issues. One of the general tendencies to find the general term asymptotic behaviour, when its ordering number grows unboundedly, is the integral representation over a generating function which does not depend on individual sequence elements. This is tried to be done almost for all types of recursions, even though the linear cases gain more importance than the others because they can be more effectively investigated by using many linear algebraic tools. Despite this may seem somehow to be rather trivial, there are a lot of theoretical fine tuning issues in the construction of true integral representations over true intervals on real axis or paths in complex domains. This work is devoted to focus on this issue starting from scratch for better understanding of the matter. The example cases are chosen to best illuminate the situations to get information for future generalization even though the work can be considered at somehow introductory level.

  8. Competitive binding of antagonistic peptides fine-tunes stomatal patterning.

    PubMed

    Lee, Jin Suk; Hnilova, Marketa; Maes, Michal; Lin, Ya-Chen Lisa; Putarjunan, Aarthi; Han, Soon-Ki; Avila, Julian; Torii, Keiko U

    2015-06-25

    During development, cells interpret complex and often conflicting signals to make optimal decisions. Plant stomata, the cellular interface between a plant and the atmosphere, develop according to positional cues, which include a family of secreted peptides called epidermal patterning factors (EPFs). How these signalling peptides orchestrate pattern formation at a molecular level remains unclear. Here we report in Arabidopsis that Stomagen (also called EPF-LIKE9) peptide, which promotes stomatal development, requires ERECTA (ER)-family receptor kinases and interferes with the inhibition of stomatal development by the EPIDERMAL PATTERNING FACTOR 2 (EPF2)-ER module. Both EPF2 and Stomagen directly bind to ER and its co-receptor TOO MANY MOUTHS. Stomagen peptide competitively replaced EPF2 binding to ER. Furthermore, application of EPF2, but not Stomagen, elicited rapid phosphorylation of downstream signalling components in vivo. Our findings demonstrate how a plant receptor agonist and antagonist define inhibitory and inductive cues to fine-tune tissue patterning on the plant epidermis. PMID:26083750

  9. Fine tuning chloroplast movements through physical interactions between phototropins

    PubMed Central

    Sztatelman, Olga; Łabuz, Justyna; Hermanowicz, Paweł; Banaś, Agnieszka Katarzyna; Bażant, Aneta; Zgłobicki, Piotr; Aggarwal, Chhavi; Nadzieja, Marcin; Krzeszowiec, Weronika; Strzałka, Wojciech; Gabryś, Halina

    2016-01-01

    Phototropins are plant photoreceptors which regulate numerous responses to blue light, including chloroplast relocation. Weak blue light induces chloroplast accumulation, whereas strong light leads to an avoidance response. Two Arabidopsis phototropins are characterized by different light sensitivities. Under continuous light, both can elicit chloroplast accumulation, but the avoidance response is controlled solely by phot2. As well as continuous light, brief light pulses also induce chloroplast displacements. Pulses of 0.1s and 0.2s of fluence rate saturating the avoidance response lead to transient chloroplast accumulation. Longer pulses (up to 20s) trigger a biphasic response, namely transient avoidance followed by transient accumulation. This work presents a detailed study of transient chloroplast responses in Arabidopsis. Phototropin mutants display altered chloroplast movements as compared with the wild type: phot1 is characterized by weaker responses, while phot2 exhibits enhanced chloroplast accumulation, especially after 0.1s and 0.2s pulses. To determine the cause of these differences, the abundance and phosphorylation levels of both phototropins, as well as the interactions between phototropin molecules are examined. The formation of phototropin homo- and heterocomplexes is the most plausible explanation of the observed phenomena. The physiological consequences of this interplay are discussed, suggesting the universal character of this mechanism that fine-tunes plant reactions to blue light. Additionally, responses in mutants of different protein phosphatase 2A subunits are examined to assess the role of protein phosphorylation in signaling of chloroplast movements. PMID:27406783

  10. Fine-tuning of macrophage activation using synthetic rocaglate derivatives

    PubMed Central

    Bhattacharya, Bidisha; Chatterjee, Sujoy; Devine, William G.; Kobzik, Lester; Beeler, Aaron B.; Porco, John A.; Kramnik, Igor

    2016-01-01

    Drug-resistant bacteria represent a significant global threat. Given the dearth of new antibiotics, host-directed therapies (HDTs) are especially desirable. As IFN-gamma (IFNγ) plays a central role in host resistance to intracellular bacteria, including Mycobacterium tuberculosis, we searched for small molecules to augment the IFNγ response in macrophages. Using an interferon-inducible nuclear protein Ipr1 as a biomarker of macrophage activation, we performed a high-throughput screen and identified molecules that synergized with low concentration of IFNγ. Several active compounds belonged to the flavagline (rocaglate) family. In primary macrophages a subset of rocaglates 1) synergized with low concentrations of IFNγ in stimulating expression of a subset of IFN-inducible genes, including a key regulator of the IFNγ network, Irf1; 2) suppressed the expression of inducible nitric oxide synthase and type I IFN and 3) induced autophagy. These compounds may represent a basis for macrophage-directed therapies that fine-tune macrophage effector functions to combat intracellular pathogens and reduce inflammatory tissue damage. These therapies would be especially relevant to fighting drug-resistant pathogens, where improving host immunity may prove to be the ultimate resource. PMID:27086720

  11. Pentagone internalises glypicans to fine-tune multiple signalling pathways

    PubMed Central

    Norman, Mark; Vuilleumier, Robin; Springhorn, Alexander; Gawlik, Jennifer; Pyrowolakis, George

    2016-01-01

    Tight regulation of signalling activity is crucial for proper tissue patterning and growth. Here we investigate the function of Pentagone (Pent), a secreted protein that acts in a regulatory feedback during establishment and maintenance of BMP/Dpp morphogen signalling during Drosophila wing development. We show that Pent internalises the Dpp co-receptors, the glypicans Dally and Dally-like protein (Dlp), and propose that this internalisation is important in the establishment of a long range Dpp gradient. Pent-induced endocytosis and degradation of glypicans requires dynamin- and Rab5, but not clathrin or active BMP signalling. Thus, Pent modifies the ability of cells to trap and transduce BMP by fine-tuning the levels of the BMP reception system at the plasma membrane. In addition, and in accordance with the role of glypicans in multiple signalling pathways, we establish a requirement of Pent for Wg signalling. Our data propose a novel mechanism by which morphogen signalling is regulated. DOI: http://dx.doi.org/10.7554/eLife.13301.001 PMID:27269283

  12. P2 receptor web: complexity and fine-tuning.

    PubMed

    Volonté, Cinzia; Amadio, Susanna; D'Ambrosi, Nadia; Colpi, Monica; Burnstock, Geoffrey

    2006-10-01

    The present review offers a new perspective on a family of receptors, termed P2 receptors, specific for nucleoside tri- and diphosphates of purines/pyrimidines. We emphasize here that while decoding the inputs of various related extracellular ligands, P2 receptors are a clear example of increasing biological complexity. They are represented by 7 ionotropic P2X and 8 metabotropic P2Y receptors; they have very heterogeneous ligands and binding characteristics, molecular properties, transduction mechanisms, cellular localization and protein-protein interactions. While the reason for this sophistication is unknown, a few compelling issues emerge while looking at such a rich variety. We ask, for instance, why so many different receptor subtypes are necessary for triggering biological properties and functions, and if these receptors are more than the sum of their single entities. A first possibility is that newly synthesized P2 proteins are casually located on the cell surface (stochastic hypothesis). Alternatively, distinct subunits are engaged on different cell phenotypes by genetic control (genetic determinism) and/or selective recruitment under physiopathological conditions and epigenetic stimuli (epigenetic determinism). Nevertheless, an appropriate way to both dissect the vast biological scenario and molecular complexity among P2 receptors and to integrate and upgrade their assortment is to regard them as a "combinatorial receptor web", that is, a dynamic architecture of P2 proteins demonstrating economic efficiency and involving a process of "fine-tuning", a mechanism which endorses the dynamic nature of all biological reactions. In the present analysis, we stimulate a scientific query about what contributes to such a vast P2 receptor sophistication. PMID:16780954

  13. SUSY models under siege: LHC constraints and electroweak fine-tuning

    NASA Astrophysics Data System (ADS)

    Baer, Howard; Barger, Vernon; Mickelson, Dan; Padeffke-Kirkland, Maren

    2014-06-01

    Recent null results from LHC8 supersymmetry (SUSY) searches along with the discovery of a standard model (SM)-like Higgs boson with mass mh≃125.5 GeV indicates sparticle masses in the TeV range, causing tension with conventional measures of electroweak fine-tuning. We propose a simple fine-tuning rule which should be followed under any credible evaluation of fine-tuning. We believe that overestimates of electroweak fine-tuning by conventional measures all arise from violations of this rule. We show that to gain accord with the fine-tuning rule, then both the Higgs mass and the traditional ΔBG fine-tuning measures reduce to the model-independent electroweak fine-tuning measure ΔEW. This occurs by combining dependent contributions to mZ or mh into independent units. Then, using ΔEW, we evaluate EW fine-tuning for a variety of SUSY models including mSUGRA, NUHM1, NUHM2, mGMSB, mAMSB, hyper-charged AMSB, gaugino AMSB and nine cases of mixed moduli-anomaly (mirage) mediated SUSY breaking models while respecting LHC Higgs mass and B-decay constraints (we do not impose LHC8 sparticle mass constraints due to the possibility of compressed spectra within many of these models). We find mSUGRA, mGMSB and the AMSB models all to be highly fine-tuned. The NUHM1 model is moderately fine-tuned while NUHM2 which allows for radiatively driven naturalness (RNS) allows for fine-tuning at a meager 10% level in the case where m(Higgsinos)˜100-200 GeV and the TeV-scale top squarks are well mixed. Models with RNS may or may not be detectable at LHC14. A √s ˜500 GeV e+e- collider will be required to make a definitive search for the requisite light Higgsinos.

  14. Tuning the Spring Constant of Cantilever-free Probe Arrays

    NASA Astrophysics Data System (ADS)

    Eichelsdoerfer, Daniel J.; Brown, Keith A.; Boya, Radha; Shim, Wooyoung; Mirkin, Chad A.

    2013-03-01

    The versatility of atomic force microscope (AFM) based techniques such as scanning probe lithography is due in part to the utilization of a cantilever that can be fabricated to match a desired application. In contrast, cantilever-free scanning probe lithography utilizes a low cost array of probes on a compliant backing layer that allows for high throughput nanofabrication but lacks the tailorability afforded by the cantilever in traditional AFM. Here, we present a method to measure and tune the spring constant of probes in a cantilever-free array by adjusting the mechanical properties of the underlying elastomeric layer. Using this technique, we are able to fabricate large-area silicon probe arrays with spring constants that can be tuned in the range from 7 to 150 N/m. This technique offers an advantage in that the spring constant depends linearly on the geometry of the probe, which is in contrast to traditional cantilever-based lithography where the spring constant varies as the cube of the beam width and thickness. To illustrate the benefit of utilizing a probe array with a lower spring constant, we pattern a block copolymer on a delicate 50 nm thick silicon nitride window.

  15. Fine-tuned Bee-Flower Coevolutionary State Hidden within Multiple Pollination Interactions

    PubMed Central

    Shimizu, Akira; Dohzono, Ikumi; Nakaji, Masayoshi; Roff, Derek A.; Miller III, Donald G.; Osato, Sara; Yajima, Takuya; Niitsu, Shûhei; Utsugi, Nozomu; Sugawara, Takashi; Yoshimura, Jin

    2014-01-01

    Relationships between flowers and pollinators are generally considered cases of mutualism since both agents gain benefits. Fine-tuned adaptations are usually found in the form of strict one-to-one coevolution between species. Many insect pollinators are, however, considered generalists, visiting numerous kinds of flowers, and many flower species (angiosperms) are also considered generalists, visited by many insect pollinators. We here describe a fine-tuned coevolutionary state of a flower-visiting bee that collects both nectar and pollen from an early spring flower visited by multiple pollinators. Detailed morphology of the bee proboscis is shown to be finely adjusted to the floral morphology and nectar production of the flower. Behavioral observations also confirm the precision of this mutualism. Our results suggest that a fine-tuned one-to-one coevolutionary state between a flower species and a pollinator species might be common, but frequently overlooked, in multiple flower-pollinator interactions. PMID:24496444

  16. Fine-tuned bee-flower coevolutionary state hidden within multiple pollination interactions.

    PubMed

    Shimizu, Akira; Dohzono, Ikumi; Nakaji, Masayoshi; Roff, Derek A; Miller, Donald G; Osato, Sara; Yajima, Takuya; Niitsu, Shûhei; Utsugi, Nozomu; Sugawara, Takashi; Yoshimura, Jin

    2014-01-01

    Relationships between flowers and pollinators are generally considered cases of mutualism since both agents gain benefits. Fine-tuned adaptations are usually found in the form of strict one-to-one coevolution between species. Many insect pollinators are, however, considered generalists, visiting numerous kinds of flowers, and many flower species (angiosperms) are also considered generalists, visited by many insect pollinators. We here describe a fine-tuned coevolutionary state of a flower-visiting bee that collects both nectar and pollen from an early spring flower visited by multiple pollinators. Detailed morphology of the bee proboscis is shown to be finely adjusted to the floral morphology and nectar production of the flower. Behavioral observations also confirm the precision of this mutualism. Our results suggest that a fine-tuned one-to-one coevolutionary state between a flower species and a pollinator species might be common, but frequently overlooked, in multiple flower-pollinator interactions. PMID:24496444

  17. Tuning the 3D plasmon field of nanohole arrays

    NASA Astrophysics Data System (ADS)

    Couture, Maxime; Liang, Yuzhang; Poirier Richard, Hugo-Pierre; Faid, Rita; Peng, Wei; Masson, Jean-Francois

    2013-11-01

    Modern photonics is being revolutionized through the use of nanostructured plasmonic materials, which confine light to sub-diffraction limit resolution providing universal, sensitive, and simple transducers for molecular sensors. Understanding the mechanisms by which light interacts with plasmonic crystals is essential for developing application-focussed devices. The strong influence of grating coupling on electromagnetic field distribution, frequency and degeneracy of plasmon bands has now been characterized using hexagonal nanohole arrays. An equation for nanohole arrays was derived to demonstrate the strong influence of incidence and rotation angle on optical properties of 2D plasmonic crystals such as nanohole arrays. Consequently, we report experimental data that are in strong agreement with finite difference time-domain (FDTD) simulations that clearly demonstrate the influence of the grating coupling conditions on the optical properties (such as plasmon degeneracy and bandwidth), and on the distribution of the plasmon field around nanohole arrays (including tuneable penetration depths and highly localized fields). The tuneable 3D plasmon field allowed for controlled sensing properties and by increasing the angle of incidence to 30 degrees, the resonance wavelength was tuned from 1000 to 600 nm, and the sensitivity was enhanced by nearly 300% for a protein assay using surface plasmon resonance (SPR) and by 40% with surface-enhanced Raman scattering (SERS) sensors.Modern photonics is being revolutionized through the use of nanostructured plasmonic materials, which confine light to sub-diffraction limit resolution providing universal, sensitive, and simple transducers for molecular sensors. Understanding the mechanisms by which light interacts with plasmonic crystals is essential for developing application-focussed devices. The strong influence of grating coupling on electromagnetic field distribution, frequency and degeneracy of plasmon bands has now been

  18. Does inflation solve the hot big bang model's fine-tuning problems?

    NASA Astrophysics Data System (ADS)

    McCoy, C. D.

    2015-08-01

    Cosmological inflation is widely considered an integral and empirically successful component of contemporary cosmology. It was originally motivated (and usually still is) by its solution of certain so-called fine-tuning problems of the hot big bang model, particularly what are known as the horizon problem and the flatness problem. Although the physics behind these problems is clear enough, the nature of the problems depends on the sense in which the hot big bang model is fine-tuned and how the alleged fine-tuning is problematic. Without clear explications of these, it remains unclear precisely what problems inflationary theory is meant to be solving and whether it does in fact solve them. I analyze the structure of these problems and consider various interpretations that may substantiate the alleged fine-tuning. On the basis of this analysis I argue that at present there is no unproblematic interpretation available for which it can be said that inflation solves the big bang model's alleged fine-tuning problems.

  19. Improving the fine tuning in models of low energy gauge mediated supersymmetry breaking

    NASA Astrophysics Data System (ADS)

    Agashe, K.; Graesser, M.

    1997-02-01

    The fine tuning in models of low energy gauge mediated supersymmetry breaking required to btain the correct Z mass is quantified. To alleviate the fine tuning problem, a model with split ( 5 + overline5) messenger fields is presented. This model has additional triplets in the low energy theory which get a mass of O(500) GeV from a coupling to a singlet. The improvement in fine tuning is quantified and the spectrum in this model is discussed. The same model with the above singlet coupled to the Higgs doublets to generate the μ term is also discussed. A Grand Unified version of the model is constructed and a known doublet-triplet splitting mechanism is used to split the messenger (5 + overline5)' s. A complete model is presented and some phenomenological constraints are discussed.

  20. Localized electrical fine tuning of passive microwave and radio frequency devices

    DOEpatents

    Findikoglu, Alp T.

    2001-04-10

    A method and apparatus for the localized electrical fine tuning of passive multiple element microwave or RF devices in which a nonlinear dielectric material is deposited onto predetermined areas of a substrate containing the device. An appropriate electrically conductive material is deposited over predetermined areas of the nonlinear dielectric and the signal line of the device for providing electrical contact with the nonlinear dielectric. Individual, adjustable bias voltages are applied to the electrically conductive material allowing localized electrical fine tuning of the devices. The method of the present invention can be applied to manufactured devices, or can be incorporated into the design of the devices so that it is applied at the time the devices are manufactured. The invention can be configured to provide localized fine tuning for devices including but not limited to coplanar waveguides, slotline devices, stripline devices, and microstrip devices.

  1. Highly Stable and Finely Tuned Magnetic Fields Generated by Permanent Magnet Assemblies

    NASA Astrophysics Data System (ADS)

    Danieli, E.; Perlo, J.; Blümich, B.; Casanova, F.

    2013-05-01

    Permanent magnetic materials are the only magnetic source that can be used to generate magnetic fields without power consumption or maintenance. Such stand-alone magnets are very attractive for many scientific and engineering areas, but they suffer from poor temporal field stability, which arises from the strong sensitivity of the magnetic materials and mechanical support to temperature variation. In this work, we describe a highly efficient method useful to cancel the temperature coefficient of permanent magnet assemblies in a passive and accurate way. It is based on the combination of at least two units made of magnetic materials with different temperature coefficients arranged in such a way that the ratio of the fields generated by each unit matches the ratio of their effective temperature coefficients defined by both the magnetic and mechanical contributions. Although typically available magnetic materials have negative temperature coefficients, the cancellation is achieved by aligning the fields generated by each unit in the opposite direction. We demonstrate the performance of this approach by stabilizing the field generated by a dipolar Halbach magnet, recently proposed to achieve high field homogeneity. Both the field drift and the homogeneity are monitored via nuclear magnetic resonance spectroscopy experiments. The results demonstrate the compatibility of the thermal compensation approach with existing strategies useful to fine-tune the spatial dependence of the field generated by permanent magnet arrays.

  2. Highly stable and finely tuned magnetic fields generated by permanent magnet assemblies.

    PubMed

    Danieli, E; Perlo, J; Blümich, B; Casanova, F

    2013-05-01

    Permanent magnetic materials are the only magnetic source that can be used to generate magnetic fields without power consumption or maintenance. Such stand-alone magnets are very attractive for many scientific and engineering areas, but they suffer from poor temporal field stability, which arises from the strong sensitivity of the magnetic materials and mechanical support to temperature variation. In this work, we describe a highly efficient method useful to cancel the temperature coefficient of permanent magnet assemblies in a passive and accurate way. It is based on the combination of at least two units made of magnetic materials with different temperature coefficients arranged in such a way that the ratio of the fields generated by each unit matches the ratio of their effective temperature coefficients defined by both the magnetic and mechanical contributions. Although typically available magnetic materials have negative temperature coefficients, the cancellation is achieved by aligning the fields generated by each unit in the opposite direction. We demonstrate the performance of this approach by stabilizing the field generated by a dipolar Halbach magnet, recently proposed to achieve high field homogeneity. Both the field drift and the homogeneity are monitored via nuclear magnetic resonance spectroscopy experiments. The results demonstrate the compatibility of the thermal compensation approach with existing strategies useful to fine-tune the spatial dependence of the field generated by permanent magnet arrays. PMID:23683185

  3. Fine-tuning anti-tumor immunotherapies via stochastic simulations

    PubMed Central

    2012-01-01

    Background Anti-tumor therapies aim at reducing to zero the number of tumor cells in a host within their end or, at least, aim at leaving the patient with a sufficiently small number of tumor cells so that the residual tumor can be eradicated by the immune system. Besides severe side-effects, a key problem of such therapies is finding a suitable scheduling of their administration to the patients. In this paper we study the effect of varying therapy-related parameters on the final outcome of the interplay between a tumor and the immune system. Results This work generalizes our previous study on hybrid models of such an interplay where interleukins are modeled as a continuous variable, and the tumor and the immune system as a discrete-state continuous-time stochastic process. The hybrid model we use is obtained by modifying the corresponding deterministic model, originally proposed by Kirschner and Panetta. We consider Adoptive Cellular Immunotherapies and Interleukin-based therapies, as well as their combination. By asymptotic and transitory analyses of the corresponding deterministic model we find conditions guaranteeing tumor eradication, and we tune the parameters of the hybrid model accordingly. We then perform stochastic simulations of the hybrid model under various therapeutic settings: constant, piece-wise constant or impulsive infusion and daily or weekly delivery schedules. Conclusions Results suggest that, in some cases, the delivery schedule may deeply impact on the therapy-induced tumor eradication time. Indeed, our model suggests that Interleukin-based therapies may not be effective for every patient, and that the piece-wise constant is the most effective delivery to stimulate the immune-response. For Adoptive Cellular Immunotherapies a metronomic delivery seems more effective, as it happens for other anti-angiogenesis therapies and chemotherapies, and the impulsive delivery seems more effective than the piece-wise constant. The expected synergistic

  4. Fine-Tuning Language Policy in Hong Kong Education: Stakeholders' Perceptions, Practices and Challenges

    ERIC Educational Resources Information Center

    Chan, Jim Y. H.

    2014-01-01

    The present study evaluates the impact of the fine-tuning medium of instruction (MOI) policy in Hong Kong in the early stages of its implementation. It explores the key stakeholders' perspectives on a school-based policy via a case study, which gathered multiple sources of qualitative data (i.e. focus groups/interviews, open-ended…

  5. Emission wavelength tuning of fluorescence by fine structural control of optical metamaterials with Fano resonance.

    PubMed

    Moritake, Y; Kanamori, Y; Hane, K

    2016-01-01

    We demonstrated fine emission wavelength tuning of quantum dot (QD) fluorescence by fine structural control of optical metamaterials with Fano resonance. An asymmetric-double-bar (ADB), which was composed of only two bars with slightly different bar lengths, was used to obtain Fano resonance in the optical region. By changing the short bar length of ADB structures with high dimensional accuracy in the order of 10 nm, resonant wavelengths of Fano resonance were controlled from 1296 to 1416 nm. Fluorescence of QDs embedded in a polymer layer on ADB metamaterials were modified due to coupling to Fano resonance and fine tuning from 1350 to 1376 nm was observed. Wavelength tuning of modified fluorescence was reproduced by analysis using absorption peaks of Fano resonance. Tuning range of modified fluorescence became narrow, which was interpreted by a simple Gaussian model and resulted from comparable FWHM in QD fluorescence and Fano resonant peaks. The results will help the design and fabrication of metamaterial devices with fluorophores such as light sources and biomarkers. PMID:27622503

  6. Dynamical fine-tuning of initial conditions for small field inflation

    NASA Astrophysics Data System (ADS)

    Iso, Satoshi; Kohri, Kazunori; Shimada, Kengo

    2016-04-01

    Small-field inflation (SFI) is widely considered to be unnatural because an extreme fine-tuning of the initial condition is necessary for sufficiently large e -folding. In this paper, we show that the unnaturally looking initial condition can be dynamically realized without any fine-tuning if the SFI occurs after rapid oscillations of the inflaton field and particle creations by preheating. In fact, if the inflaton field ϕ is coupled to another scalar field χ through the interaction g2χ2ϕ2 and the vacuum energy during the small field inflation is given by λ M4, the initial value can be dynamically set at (√{λ }/g )M2/Mpl, which is much smaller than the typical scale of the potential M . This solves the initial condition problem in the new inflation model or some classes of the hilltop inflation models.

  7. The HIGGS Boson Mass at 2 Loops in the Finely Tuned Split Supersymmetric Standard Model

    SciTech Connect

    Binger, M

    2004-09-08

    The mass of the Higgs boson in the finely tuned Split Supersymmetric Standard Model is calculated. All 1 loop threshold effects are included, in addition to the full RG running of the Higgs quartic coupling through 2 loops. The 2 loop corrections are very small, typically less than 1GeV. The 1 loop threshold corrections to the top yukawa coupling and the Higgs mass generally push the Higgs mass down a few GeV.

  8. An Undecanuclear Ferrimagnetic Cu9Dy2 Single Molecule Magnet Achieved through Ligand Fine-Tuning.

    PubMed

    Kühne, Irina A; Kostakis, George E; Anson, Christopher E; Powell, Annie K

    2016-05-01

    We describe the concept of increasing the nuclearity of a previously reported high-spin Cu5Gd2 core using a "fine-tuning" ligand approach. Thus, two Cu9Ln2 coordination clusters, with Ln = Dy (1) and Gd (2), were synthesized with the Gd compound having a ground spin state of (17)/2 and the Dy analogue showing single-molecule-magnet behavior in zero field. PMID:27096219

  9. Fine-tuned grayscale optofluidic maskless lithography for three-dimensional freeform shape microstructure fabrication.

    PubMed

    Song, Suk-Heung; Kim, Kibeom; Choi, Sung-Eun; Han, Sangkwon; Lee, Ho-Suk; Kwon, Sunghoon; Park, Wook

    2014-09-01

    This article presents free-floating three-dimensional (3D) microstructure fabrication in a microfluidic channel using direct fine-tuned grayscale image lithography. The image is designed as a freeform shape and is composed of gray shades as light-absorbing features. Gray shade levels are modulated through multiple reflections of light in a digital micromirror device (DMD) to produce different height formations. Whereas conventional photolithography has several limitations in producing grayscale colors on photomask features, our method focuses on a maskless, single-shot process for fabrication of freeform 3D micro-scale shapes. The fine-tuned gray image is designed using an 8-bit grayscale color; thus, each pixel is capable of displaying 256 gray shades. The pattern of the UV light reflecting on the DMD is transferred to a photocurable resin flowing through a microfluidic channel. Here, we demonstrate diverse free-floating 3D microstructure fabrication using fine-tuned grayscale image lithography. Additionally, we produce polymeric microstructures with locally embedded gray encoding patterns, such as grayscale-encoded microtags. This functional microstructure can be applied to a biophysical detection system combined with 3D microstructures. This method would be suitable for fabricating 3D microstructures that have a specific morphology to be used for particular biological or medical applications. PMID:25166099

  10. Fine-tuning of magnetic and microfluidic viscous forces for specific magnetic bead-based immunocomplex formation

    NASA Astrophysics Data System (ADS)

    Cornaglia, M.; Tekin, H. C.; Lehnert, T.; Gijs, M. A. M.

    2013-08-01

    We investigate the working principle of a novel type of microfluidic sandwich immunoassay, as used for the detection of biomarkers. The heterogeneous assay is based on the specific interactions between an array of functionalized superparamagnetic beads and a flow of secondary superparamagnetic beads that carry the antigens and are simultaneously used as detection labels. We identify the main forces governing the immunoassay performance and develop a combined finite element method/analytical model to predict and control these forces. The clue for the improved assay specificity is in the fine-tuning of inter-bead magnetic dipolar and microfluidic viscous forces, which allows strongly reducing non-specific interactions, while enhancing the specific formation of immunocomplexes. We exploit our theoretical model to explain the enhanced sensitivity of magnetic bead-based immunoassay experiments performed in microfluidic chips.

  11. Fine-tuning with brane-localized flux in 6D supergravity

    NASA Astrophysics Data System (ADS)

    Niedermann, Florian; Schneider, Robert

    2016-02-01

    There are claims in the literature that the cosmological constant problem could be solved in a braneworld model with two large (micron-sized) supersymmetric extra dimensions. The mechanism relies on two basic ingredients: first, the cosmological constant only curves the compact bulk geometry into a rugby shape while the 4D curvature stays flat. Second, a brane-localized flux term is introduced in order to circumvent Weinberg's fine-tuning argument, which otherwise enters here through a backdoor via the flux quantization condition. In this paper, we show that the latter mechanism does not work in the way it was designed: the only localized flux coupling that guarantees a flat on-brane geometry is one which preserves the scale invariance of the bulk theory. Consequently, Weinberg's argument applies, making a fine-tuning necessary again. The only remaining window of opportunity lies within scale invariance breaking brane couplings, for which the tuning could be avoided. Whether the corresponding 4D curvature could be kept under control and in agreement with the observed value will be answered in our companion paper [1].

  12. Fine-tuning the etch depth profile via dynamic shielding of ion beam

    NASA Astrophysics Data System (ADS)

    Wu, Lixiang; Qiu, Keqiang; Fu, Shaojun

    2016-08-01

    We introduce a method for finely adjusting the etch depth profile by dynamic shielding in the course of ion beam etching (IBE), which is crucial for the ultra-precision fabrication of large optics. We study the physical process of dynamic shielding and propose a parametric modeling method to quantitatively analyze the shielding effect on etch depths, or rather the shielding rate, where a piecewise Gaussian model is adopted to fit the shielding rate profile. Two experiments were conducted. The experimental result of parametric modeling of shielding rate profiles shows that the shielding rate profile is significantly influenced by the rotary angle of the leaf. The result of the experiment on fine-tuning the etch depth profile shows good agreement with the simulated result, which preliminarily verifies the feasibility of our method.

  13. Nonparametric Fine Tuning of Mixtures: Application to Non-Life Insurance Claims Distribution Estimation

    NASA Astrophysics Data System (ADS)

    Sardet, Laure; Patilea, Valentin

    When pricing a specific insurance premium, actuary needs to evaluate the claims cost distribution for the warranty. Traditional actuarial methods use parametric specifications to model claims distribution, like lognormal, Weibull and Pareto laws. Mixtures of such distributions allow to improve the flexibility of the parametric approach and seem to be quite well-adapted to capture the skewness, the long tails as well as the unobserved heterogeneity among the claims. In this paper, instead of looking for a finely tuned mixture with many components, we choose a parsimonious mixture modeling, typically a two or three-component mixture. Next, we use the mixture cumulative distribution function (CDF) to transform data into the unit interval where we apply a beta-kernel smoothing procedure. A bandwidth rule adapted to our methodology is proposed. Finally, the beta-kernel density estimate is back-transformed to recover an estimate of the original claims density. The beta-kernel smoothing provides an automatic fine-tuning of the parsimonious mixture and thus avoids inference in more complex mixture models with many parameters. We investigate the empirical performance of the new method in the estimation of the quantiles with simulated nonnegative data and the quantiles of the individual claims distribution in a non-life insurance application.

  14. Fine-tune lens-heating-induced focus drift with different process and illumination settings

    NASA Astrophysics Data System (ADS)

    Cui, Yuanting

    2001-09-01

    This study is to establish the relationship of lens heating (LH) performance with related process variables and develop the methodology for reducing LH induced focus drift for different products based on ASML LH algorithms and experiment data. Focus drift data is collected at certain LH machine constants for different process settings, such as different clear window images (CLW) in stepper jobs, different exposure doses, reticle transmission rates, and substrates. The further study is done at different illumination settings to establish the correlation between NA/sigma settings, focus drift and LH scaling factors ((mu) 1 (mu) 2). The characteristic (mu) 1, (mu) 2 -- NA/Ill relationship for this i-line stepper is generated using production batches. LH machine constants are fine-tuned based on the Poly layer for 0.30 micrometer Logic Mix-mode, 0.30 micrometer SRAM and 0.35 micrometer Embedded SRAM products. This work provides an accurate and practical way to fine-tune LH for all the i-line/DUV steppers based on the critical layer of representative products in a foundry fab.

  15. Anthropic Reasoning about Fine-Tuning, and Neoclassical Cosmology: Providence, Omnipresence, and Observation Selection Theory

    NASA Astrophysics Data System (ADS)

    Walker, Theodore, Jr.

    2011-10-01

    Anthropic reasoning about observation selection effects upon the appearance of cosmic providential fine-tuning (fine-tuning that provides for life) is often motivated by a desire to avoid theological implications (implications favoring the idea of a divine cosmic provider) without appealing to sheer lucky-for-us-cosmic-jackpot happenstance and coincidence. Cosmic coincidence can be rendered less incredible by appealing to a multiverse context. Cosmic providence can be rendered non-theological by appealing to an agent-less providential purpose, or by appealing to less-than-omnipresent/local providers, such as alien intelligences creating life- providing baby universes. Instead of choosing either cosmic coincidence or cosmic providence, as though they were mutually exclusive; it is better to accept both. Neoclassical thought accepts coincidence and providence, plus many local providers and one omnipresent provider. Moreover, fundamental observation selection theory should distinguish the many local observers of some events from the one omnipresent observer of all events. Accepting both coincidence and providence avoids classical theology (providence without coincidence) and classical atheism (coincidence without providence), but not neoclassical theology (providence with coincidence). Cosmology cannot avoid the idea of an all-inclusive omnipresent providential dice-throwing living-creative whole of reality, an idea essential to neoclassical theology, and to neoclassical cosmology.

  16. An intramolecular disulfide bond designed in myoglobin fine-tunes both protein structure and peroxidase activity.

    PubMed

    Wu, Lei-Bin; Yuan, Hong; Zhou, Hu; Gao, Shu-Qin; Nie, Chang-Ming; Tan, Xiangshi; Wen, Ge-Bo; Lin, Ying-Wu

    2016-06-15

    Disulfide bond plays crucial roles in stabilization of protein structure and in fine-tuning protein functions. To explore an approach for rational heme protein design, we herein rationally introduced a pair of cysteines (F46C/M55C) into the scaffold of myoglobin (Mb), mimicking those in native neuroglobin. Molecular modeling suggested that it is possible for Cys46 and Cys55 to form an intramolecular disulfide bond, which was confirmed experimentally by ESI-MS analysis, DTNB reaction and CD spectrum. Moreover, it was shown that the spontaneously formed disulfide bond of Cys46-Cys55 fine-tunes not only the heme active site structure, but also the protein functions. The substitution of Phe46 with Ser46 in F46S Mb destabilizes the protein while facilitates H2O2 activation. Remarkably, the formation of an intramolecular disulfide bond of Cys46-Cys55 in F46C/M55C Mb improves the protein stability and regulates the heme site to be more favorable for substrate binding, resulting in enhanced peroxidase activity. This study provides valuable information of structure-function relationship for heme proteins regulated by an intramolecular disulfide bond, and also suggests that construction of such a covalent bond is useful for design of functional heme proteins. PMID:27117233

  17. Fine-Tuning of FACT by the Ubiquitin Proteasome System in Regulation of Transcriptional Elongation.

    PubMed

    Sen, Rwik; Ferdoush, Jannatul; Kaja, Amala; Bhaumik, Sukesh R

    2016-06-01

    FACT (facilitates chromatin transcription), an evolutionarily conserved histone chaperone involved in transcription and other DNA transactions, is upregulated in cancers, and its downregulation is associated with cellular death. However, it is not clearly understood how FACT is fine-tuned for normal cellular functions. Here, we show that the FACT subunit Spt16 is ubiquitylated by San1 (an E3 ubiquitin ligase) and degraded by the 26S proteasome. Enhanced abundance of Spt16 in the absence of San1 impairs transcriptional elongation. Likewise, decreased abundance of Spt16 also reduces transcription. Thus, an optimal level of Spt16 is required for efficient transcriptional elongation, which is maintained by San1 via ubiquitylation and proteasomal degradation. Consistently, San1 associates with the coding sequences of active genes to regulate Spt16's abundance. Further, we found that enhanced abundance of Spt16 in the absence of San1 impairs chromatin reassembly at the coding sequence, similarly to the results seen following inactivation of Spt16. Efficient chromatin reassembly enhances the fidelity of transcriptional elongation. Taken together, our results demonstrate for the first time a fine-tuning of FACT by a ubiquitin proteasome system in promoting chromatin reassembly in the wake of elongating RNA polymerase II and transcriptional elongation, thus revealing novel regulatory mechanisms of gene expression. PMID:27044865

  18. Promoter library designed for fine-tuned gene expression in Pichia pastoris

    PubMed Central

    Hartner, Franz S.; Ruth, Claudia; Langenegger, David; Johnson, Sabrina N.; Hyka, Petr; Lin-Cereghino, Geoffrey P.; Lin-Cereghino, Joan; Kovar, Karin; Cregg, James M.; Glieder, Anton

    2008-01-01

    Although frequently used as protein production host, there is only a limited set of promoters available to drive the expression of recombinant proteins in Pichia pastoris. Fine-tuning of gene expression is often needed to maximize product yield and quality. However, for efficient knowledge-based engineering, a better understanding of promoter function is indispensable. Consequently, we created a promoter library by deletion and duplication of putative transcription factor-binding sites within the AOX1 promoter (PAOX1) sequence. This first library initially spanned an activity range between ∼6% and >160% of the wild-type promoter activity. After characterization of the promoter library employing a green fluorescent protein (GFP) variant, the new regulatory toolbox was successfully utilized in a ‘real case’, i.e. the expression of industrial enzymes. Characterization of the library under repressing, derepressing and inducing conditions displayed at least 12 cis-acting elements involved in PAOX1-driven high-level expression. Based on this deletion analysis, novel short artificial promoter variants were constructed by combining cis-acting elements with basal promoter. In addition to improving yields and quality of heterologous protein production, the new PAOX1 synthetic promoter library constitutes a basic toolbox to fine-tune gene expression in metabolic engineering and sequential induction of protein expression in synthetic biology. PMID:18539608

  19. Adiponectin fine-tuning of liver regeneration dynamics revealed through cellular network modelling.

    PubMed

    Correnti, Jason M; Cook, Daniel; Aksamitiene, Edita; Swarup, Aditi; Ogunnaike, Babatunde; Vadigepalli, Rajanikanth; Hoek, Jan B

    2015-01-15

    Following partial hepatectomy, the liver initiates a regenerative programme involving hepatocyte priming and replication driven by the coordinated actions of cytokine and growth factors. We investigated the mechanisms underlying adiponectin's (Adn) regulation of liver regeneration through modulation of these mediators. Adn(-/-) mice showed delayed onset of hepatocyte replication, but accelerated cell cycle progression relative to wild-type mice, suggesting Adn has multiple effects fine-tuning the kinetics of liver regeneration. We developed a computational model describing the molecular and physiological kinetics of liver regeneration in Adn(-/-) mice. We employed this computational model to evaluate the underlying regulatory mechanisms. Our analysis predicted that Adn is required for an efficient early cytokine response to partial hepatectomy, but is inhibitory to later growth factor actions. Consistent with this prediction, Adn knockout reduced hepatocyte responses to interleukin-6 during the priming phase, but enhanced growth factor levels through peak hepatocyte replication. By contrast, supraphysiological concentrations of Adn resulting from rosiglitazone treatment suppressed regeneration by reducing growth factor levels during S phase, consistent with computational predictions. Together, these results revealed that Adn fine-tunes the progression of liver regeneration through dynamically modulating molecular mediator networks and cellular interactions within the liver. PMID:25630259

  20. Adiponectin fine-tuning of liver regeneration dynamics revealed through cellular network modelling

    PubMed Central

    Correnti, Jason M; Cook, Daniel; Aksamitiene, Edita; Swarup, Aditi; Ogunnaike, Babatunde; Vadigepalli, Rajanikanth; Hoek, Jan B

    2015-01-01

    Following partial hepatectomy, the liver initiates a regenerative programme involving hepatocyte priming and replication driven by the coordinated actions of cytokine and growth factors. We investigated the mechanisms underlying adiponectin's (Adn) regulation of liver regeneration through modulation of these mediators. Adn–/– mice showed delayed onset of hepatocyte replication, but accelerated cell cycle progression relative to wild-type mice, suggesting Adn has multiple effects fine-tuning the kinetics of liver regeneration. We developed a computational model describing the molecular and physiological kinetics of liver regeneration in Adn–/– mice. We employed this computational model to evaluate the underlying regulatory mechanisms. Our analysis predicted that Adn is required for an efficient early cytokine response to partial hepatectomy, but is inhibitory to later growth factor actions. Consistent with this prediction, Adn knockout reduced hepatocyte responses to interleukin-6 during the priming phase, but enhanced growth factor levels through peak hepatocyte replication. By contrast, supraphysiological concentrations of Adn resulting from rosiglitazone treatment suppressed regeneration by reducing growth factor levels during S phase, consistent with computational predictions. Together, these results revealed that Adn fine-tunes the progression of liver regeneration through dynamically modulating molecular mediator networks and cellular interactions within the liver. PMID:25630259

  1. Design and fine-tuning redox potentials of metalloproteins involved in electron transfer in bioenergetics.

    PubMed

    Hosseinzadeh, Parisa; Lu, Yi

    2016-05-01

    Redox potentials are a major contributor in controlling the electron transfer (ET) rates and thus regulating the ET processes in the bioenergetics. To maximize the efficiency of the ET process, one needs to master the art of tuning the redox potential, especially in metalloproteins, as they represent major classes of ET proteins. In this review, we first describe the importance of tuning the redox potential of ET centers and its role in regulating the ET in bioenergetic processes including photosynthesis and respiration. The main focus of this review is to summarize recent work in designing the ET centers, namely cupredoxins, cytochromes, and iron-sulfur proteins, and examples in design of protein networks involved these ET centers. We then discuss the factors that affect redox potentials of these ET centers including metal ion, the ligands to metal center and interactions beyond the primary ligand, especially non-covalent secondary coordination sphere interactions. We provide examples of strategies to fine-tune the redox potential using both natural and unnatural amino acids and native and nonnative cofactors. Several case studies are used to illustrate recent successes in this area. Outlooks for future endeavors are also provided. This article is part of a Special Issue entitled Biodesign for Bioenergetics--the design and engineering of electronic transfer cofactors, proteins and protein networks, edited by Ronald L. Koder and J.L. Ross Anderson. PMID:26301482

  2. Fine-Tuning of Crystal Packing and Charge Transport Properties of BDOPV Derivatives through Fluorine Substitution.

    PubMed

    Dou, Jin-Hu; Zheng, Yu-Qing; Yao, Ze-Fan; Yu, Zhi-Ao; Lei, Ting; Shen, Xingxing; Luo, Xu-Yi; Sun, Junliang; Zhang, Shi-Ding; Ding, Yi-Fan; Han, Guangchao; Yi, Yuanping; Wang, Jie-Yu; Pei, Jian

    2015-12-23

    Molecular packing in organic single crystals greatly influences their charge transport properties but can hardly be predicted and designed because of the complex intermolecular interactions. In this work, we have realized systematic fine-tuning of the single-crystal molecular packing of five benzodifurandione-based oligo(p-phenylenevinylene) (BDOPV)-based small molecules through incorporation of electronegative fluorine atoms on the BDOPV backbone. While these molecules all exhibit similar column stacking configurations in their single crystals, the intermolecular displacements and distances can be substantially modified by tuning of the amounts and/or the positions of the substituent fluorine atoms. Density functional theory calculations showed that the subtle differences in charge distribution or electrostatic potential induced by different fluorine substitutions play an important role in regulating the molecular packing of the BDOPV compounds. Consequently, the electronic couplings for electron transfer can vary from 71 meV in a slipped stack to 201 meV in a nearly cofacial antiparallel stack, leading to an increase in the electron mobility of the BDOPV derivatives from 2.6 to 12.6 cm(2) V(-1) s(-1). The electron mobility of the five molecules did not show a good correlation with the LUMO levels, indicating that the distinct difference in charge transport properties is a result of the molecular packing. Our work not only provides a series of high-electron-mobility organic semiconductors but also demonstrates that fluorination is an effective approach for fine-tuning of single-crystal packing modes beyond simply lowering the molecular energy levels. PMID:26619351

  3. Radiative natural supersymmetry: Reconciling electroweak fine-tuning and the Higgs boson mass

    NASA Astrophysics Data System (ADS)

    Baer, Howard; Barger, Vernon; Huang, Peisi; Mickelson, Dan; Mustafayev, Azar; Tata, Xerxes

    2013-06-01

    Models of natural supersymmetry seek to solve the little hierarchy problem by positing a spectrum of light Higgsinos ≲200-300GeV and light top squarks ≲600GeV along with very heavy squarks and TeV-scale gluinos. Such models have low electroweak fine-tuning and satisfy the LHC constraints. However, in the context of the minimal supersymmetric standard model, they predict too low a value of mh, are frequently in conflict with the measured b→sγ branching fraction, and the relic density of thermally produced Higgsino-like weakly interacting massive particles (WIMPs) falls well below dark matter measurements. We propose a framework dubbed radiative natural supersymmetry (RNS), which can be realized within the minimal supersymmetric standard model (avoiding the addition of extra exotic matter) and which maintains features such as gauge coupling unification and radiative electroweak symmetry breaking. The RNS model can be generated from supersymmetry (SUSY) grand unified theory type models with nonuniversal Higgs masses. Allowing for high-scale soft SUSY breaking Higgs mass mHu>m0 leads to automatic cancellations during renormalization group running and to radiatively-induced low fine-tuning at the electroweak scale. Coupled with large mixing in the top-squark sector, RNS allows for fine-tuning at the 3%-10% level with TeV-scale top squarks and a 125 GeV light Higgs scalar h. The model allows for at least a partial solution to the SUSY flavor, CP, and gravitino problems since first-/second-generation scalars (and the gravitino) may exist in the 10-30 TeV regime. We outline some possible signatures for RNS at the LHC, such as the appearance of low invariant mass opposite-sign isolated dileptons from gluino cascade decays. The smoking gun signature for RNS is the appearance of light Higgsinos at a linear e+e- collider. If the strong CP problem is solved by the Peccei-Quinn mechanism, then RNS naturally accommodates mixed axion-Higgsino cold dark matter, where the

  4. Eukaryotic initiator tRNA: finely tuned and ready for action.

    PubMed

    Kolitz, Sarah E; Lorsch, Jon R

    2010-01-21

    The initiator tRNA must serve functions distinct from those of other tRNAs, evading binding to elongation factors and instead binding directly to the ribosomal P site with the aid of initiation factors. It plays a key role in decoding the start codon, setting the frame for translation of the mRNA. Sequence elements and modifications of the initiator tRNA distinguish it from the elongator methionyl tRNA and help it to perform its varied tasks. These identity elements appear to finely tune the structure of the initiator tRNA, and growing evidence suggests that the body of the tRNA is involved in transmitting the signal that the start codon has been found to the rest of the pre-initiation complex. PMID:19925799

  5. viral silencing suppressors: Tools forged to fine-tune host-pathogen coexistence.

    PubMed

    Csorba, Tibor; Kontra, Levente; Burgyán, József

    2015-05-01

    RNA silencing is a homology-dependent gene inactivation mechanism that regulates a wide range of biological processes including antiviral defense. To deal with host antiviral responses viruses evolved mechanisms to avoid or counteract this, most notably through expression of viral suppressors of RNA silencing. Besides working as silencing suppressors, these proteins may also fulfill other functions during infection. In many cases the interplay between the suppressor function and other "unrelated" functions remains elusive. We will present host factors implicated in antiviral pathways and summarize the current status of knowledge about the diverse viral suppressors' strategies acting at various steps of antiviral silencing in plants. Besides, we will consider the multi-functionality of these versatile proteins and related biochemical processes in which they may be involved in fine-tuning the plant-virus interaction. Finally, we will present the current applications and discuss perspectives of the use of these proteins in molecular biology and biotechnology. PMID:25766638

  6. Towards a realistic solution of the cosmological constant fine-tuning problem by Higgs inflation

    NASA Astrophysics Data System (ADS)

    Feng, Chao-Jun; Li, Xin-Zhou

    2014-11-01

    Why is the cosmological constant Λ observed today so much smaller than the Planck scale, and why is the Universe accelerating at present? This is the so-called cosmological constant fine-tuning problem. In this paper, we find that this problem may be solved with the help of Higgs inflation by simply assuming a variable cosmological "constant" during the inflationary epoch. Meanwhile, it could predict a large tensor-to-scalar ratio r ≈0.20 and a large running of the spectral index ns'≈-0.028 with a red-tilt spectrum ns≈0.96 , as well as a big enough number of e -folds N ≈40 , requiring that we solve the problems in big bang cosmology with the help of Λ .

  7. The Orchestra and Its Maestro: Shigella's Fine-Tuning of the Inflammasome Platforms.

    PubMed

    Hermansson, Anna-Karin; Paciello, Ida; Bernardini, Maria Lina

    2016-01-01

    Shigella spp. are the causative agents of bacillary dysentery, leading to extensive mortality and morbidity worldwide. These facultative intracellular bacteria invade the epithelium of the colon and the rectum, inducing a severe inflammatory response from which the symptoms of the disease originate. Shigella are human pathogens able to manipulate and subvert the innate immune system surveillance. Shigella dampens inflammasome activation in epithelial cells. In infected macrophages, inflammasome activation and IL-1β and IL-18 release lead to massive neutrophil recruitment and greatly contribute to inflammation. Here, we describe how Shigella hijacks and finely tunes inflammasome activation in the different cell populations involved in pathogenesis: epithelial cells, macrophages, neutrophils, DCs, and B and T lymphocytes. Shigella emerges as a "sly" pathogen that switches on/off the inflammasome mechanisms in order to optimize the interaction with the host and establish a successful infection. PMID:27460806

  8. Spectral fine tuning of cyanine dyes: electron donor-acceptor substituted analogues of thiazole orange.

    PubMed

    Rastede, Elizabeth E; Tanha, Matteus; Yaron, David; Watkins, Simon C; Waggoner, Alan S; Armitage, Bruce A

    2015-09-26

    The introduction of electron donor and acceptor groups at strategic locations on a fluorogenic cyanine dye allows fine-tuning of the absorption and emission spectra while preserving the ability of the dye to bind to biomolecular hosts such as double-stranded DNA and a single-chain antibody fragment originally selected for binding to the parent unsubstituted dye, thiazole orange (TO). The observed spectral shifts are consistent with calculated HOMO-LUMO energy gaps and reflect electron density localization on the quinoline half of TO in the LUMO. A dye bearing donating methoxy and withdrawing trifluoromethyl groups on the benzothiazole and quinoline rings, respectively, shifts the absorption spectrum to sufficiently longer wavelengths to allow excitation at green wavelengths as opposed to the parent dye, which is optimally excited in the blue. PMID:26171668

  9. Spectral Fine Tuning of Cyanine Dyes: Electron Donor-Acceptor Substituted Analogues of Thiazole Orange†

    PubMed Central

    Rastede, Elizabeth E.; Tanha, Matteus; Yaron, David; Watkins, Simon C.; Waggoner, Alan S.; Armitage, Bruce A.

    2015-01-01

    The introduction of electron donor and acceptor groups at strategic locations on a fluorogenic cyanine dye allows fine-tuning of the absorption and emission spectra while preserving the ability of the dye to bind to biomolecular hosts such as double-stranded DNA and a single-chain antibody fragment originally selected for binding to the parent unsubstituted dye, thiazole orange (TO). The observed spectral shifts are consistent with calculated HOMO-LUMO energy gaps and reflect electron density localization on the quinoline half of TO in the LUMO. A dye bearing donating methoxy and withdrawing trifluoromethyl groups on the benzothiazole and quinoline rings, respectively, shifts the absorption spectrum to sufficiently longer wavelengths to allow excitation at green wavelengths as opposed to the parent dye, which is optimally excited in the blue. PMID:26171668

  10. How SUMOylation Fine-Tunes the Fanconi Anemia DNA Repair Pathway

    PubMed Central

    Coleman, Kate E.; Huang, Tony T.

    2016-01-01

    Fanconi anemia (FA) is a rare human genetic disorder characterized by developmental defects, bone marrow failure and cancer predisposition, primarily due to a deficiency in the repair of DNA interstrand crosslinks (ICLs). ICL repair through the FA DNA repair pathway is a complicated multi-step process, involving at least 19 FANC proteins and coordination of multiple DNA repair activities, including homologous recombination, nucleotide excision repair and translesion synthesis (TLS). SUMOylation is a critical regulator of several DNA repair pathways, however, the role of this modification in controlling the FA pathway is poorly understood. Here, we summarize recent advances in the fine-tuning of the FA pathway by small ubiquitin-like modifier (SUMO)-targeted ubiquitin ligases (STUbLs) and other SUMO-related interactions, and discuss the implications of these findings in the design of novel therapeutics for alleviating FA-associated condition, including cancer. PMID:27148358

  11. Phenotypic flexibility of gape anatomy fine-tunes the aquatic prey-capture system of newts

    PubMed Central

    Van Wassenbergh, Sam; Heiss, Egon

    2016-01-01

    A unique example of phenotypic flexibility of the oral apparatus is present in newts (Salamandridae) that seasonally change between an aquatic and a terrestrial habitat. Newts grow flaps of skin between their upper and lower jaws, the labial lobes, to partly close the corners of the mouth when they adopt an aquatic lifestyle during their breeding season. Using hydrodynamic simulations based on μCT-scans and cranial kinematics during prey-capture in the smooth newt (Lissotriton vulgaris), we showed that this phenotypic flexibility is an adaptive solution to improve aquatic feeding performance: both suction distance and suction force increase by approximately 15% due to the labial lobes. As the subsequent freeing of the corners of the mouth by resorption of the labial lobes is assumed beneficial for the terrestrial capture of prey by the tongue, this flexibility of the mouth fine-tunes the process of capturing prey throughout the seasonal switching between water and land. PMID:27383663

  12. Zipf's Law and Criticality in Multivariate Data without Fine-Tuning

    NASA Astrophysics Data System (ADS)

    Schwab, David J.; Nemenman, Ilya; Mehta, Pankaj

    2014-08-01

    The joint probability distribution of states of many degrees of freedom in biological systems, such as firing patterns in neural networks or antibody sequence compositions, often follows Zipf's law, where a power law is observed on a rank-frequency plot. This behavior has been shown to imply that these systems reside near a unique critical point where the extensive parts of the entropy and energy are exactly equal. Here, we show analytically, and via numerical simulations, that Zipf-like probability distributions arise naturally if there is a fluctuating unobserved variable (or variables) that affects the system, such as a common input stimulus that causes individual neurons to fire at time-varying rates. In statistics and machine learning, these are called latent-variable or mixture models. We show that Zipf's law arises generically for large systems, without fine-tuning parameters to a point. Our work gives insight into the ubiquity of Zipf's law in a wide range of systems.

  13. Enhancement of impact strength of poly (methyl methacrylate) with surface fine-tuned nano-silica

    NASA Astrophysics Data System (ADS)

    Wen, Bin; Dong, Yixiao; Wu, Lili; Long, Chao; Zhang, Chaocan

    2015-07-01

    Highly dispersible nanoparticles in organic solvent always receive wide interests due to their compatibility with polymer materials. This paper reported a kind of isopropanol alcohol silica dispersion which obtained using a method of azeotropic distillation. The isopropanol alcohol dispersed silica (IPADS) were treated with coupling agents to fine-tune their surface properties. Polymethyl methacrylate (PMMA) was then used as a research object to test the compatibility between IPADS and polymer. UV-vis spectra indicate that IPADS would reach its high compatibility with PMMA if coupling with trimethoxypropylsilane (PTMS). Followed experiments on PMMA proved that the high compatibility can prominently enhance the impact strength about 30%. The results may provide reference both for nano-silica modification and better understanding of nano-enhanced materials.

  14. A voltage-dependent chloride channel fine-tunes photosynthesis in plants.

    PubMed

    Herdean, Andrei; Teardo, Enrico; Nilsson, Anders K; Pfeil, Bernard E; Johansson, Oskar N; Ünnep, Renáta; Nagy, Gergely; Zsiros, Ottó; Dana, Somnath; Solymosi, Katalin; Garab, Győző; Szabó, Ildikó; Spetea, Cornelia; Lundin, Björn

    2016-01-01

    In natural habitats, plants frequently experience rapid changes in the intensity of sunlight. To cope with these changes and maximize growth, plants adjust photosynthetic light utilization in electron transport and photoprotective mechanisms. This involves a proton motive force (PMF) across the thylakoid membrane, postulated to be affected by unknown anion (Cl(-)) channels. Here we report that a bestrophin-like protein from Arabidopsis thaliana functions as a voltage-dependent Cl(-) channel in electrophysiological experiments. AtVCCN1 localizes to the thylakoid membrane, and fine-tunes PMF by anion influx into the lumen during illumination, adjusting electron transport and the photoprotective mechanisms. The activity of AtVCCN1 accelerates the activation of photoprotective mechanisms on sudden shifts to high light. Our results reveal that AtVCCN1, a member of a conserved anion channel family, acts as an early component in the rapid adjustment of photosynthesis in variable light environments. PMID:27216227

  15. A voltage-dependent chloride channel fine-tunes photosynthesis in plants

    PubMed Central

    Herdean, Andrei; Teardo, Enrico; Nilsson, Anders K.; Pfeil, Bernard E.; Johansson, Oskar N.; Ünnep, Renáta; Nagy, Gergely; Zsiros, Ottó; Dana, Somnath; Solymosi, Katalin; Garab, Győző; Szabó, Ildikó; Spetea, Cornelia; Lundin, Björn

    2016-01-01

    In natural habitats, plants frequently experience rapid changes in the intensity of sunlight. To cope with these changes and maximize growth, plants adjust photosynthetic light utilization in electron transport and photoprotective mechanisms. This involves a proton motive force (PMF) across the thylakoid membrane, postulated to be affected by unknown anion (Cl−) channels. Here we report that a bestrophin-like protein from Arabidopsis thaliana functions as a voltage-dependent Cl− channel in electrophysiological experiments. AtVCCN1 localizes to the thylakoid membrane, and fine-tunes PMF by anion influx into the lumen during illumination, adjusting electron transport and the photoprotective mechanisms. The activity of AtVCCN1 accelerates the activation of photoprotective mechanisms on sudden shifts to high light. Our results reveal that AtVCCN1, a member of a conserved anion channel family, acts as an early component in the rapid adjustment of photosynthesis in variable light environments. PMID:27216227

  16. Phenotypic flexibility of gape anatomy fine-tunes the aquatic prey-capture system of newts

    NASA Astrophysics Data System (ADS)

    van Wassenbergh, Sam; Heiss, Egon

    2016-07-01

    A unique example of phenotypic flexibility of the oral apparatus is present in newts (Salamandridae) that seasonally change between an aquatic and a terrestrial habitat. Newts grow flaps of skin between their upper and lower jaws, the labial lobes, to partly close the corners of the mouth when they adopt an aquatic lifestyle during their breeding season. Using hydrodynamic simulations based on μCT-scans and cranial kinematics during prey-capture in the smooth newt (Lissotriton vulgaris), we showed that this phenotypic flexibility is an adaptive solution to improve aquatic feeding performance: both suction distance and suction force increase by approximately 15% due to the labial lobes. As the subsequent freeing of the corners of the mouth by resorption of the labial lobes is assumed beneficial for the terrestrial capture of prey by the tongue, this flexibility of the mouth fine-tunes the process of capturing prey throughout the seasonal switching between water and land.

  17. Fine tuning of the threshold of T cell selection by the Nck adapters.

    PubMed

    Roy, Edwige; Togbe, Dieudonnée; Holdorf, Amy; Trubetskoy, Dmitry; Nabti, Sabrina; Küblbeck, Günter; Schmitt, Sabine; Kopp-Schneider, Annette; Leithäuser, Frank; Möller, Peter; Bladt, Friedhelm; Hämmerling, Günter J; Arnold, Bernd; Pawson, Tony; Tafuri, Anna

    2010-12-15

    Thymic selection shapes the T cell repertoire to ensure maximal antigenic coverage against pathogens while preventing autoimmunity. Recognition of self-peptides in the context of peptide-MHC complexes by the TCR is central to this process, which remains partially understood at the molecular level. In this study we provide genetic evidence that the Nck adapter proteins are essential for thymic selection. In vivo Nck deletion resulted in a reduction of the thymic cellularity, defective positive selection of low-avidity T cells, and impaired deletion of thymocytes engaged by low-potency stimuli. Nck-deficient thymocytes were characterized by reduced ERK activation, particularly pronounced in mature single positive thymocytes. Taken together, our findings identify a crucial role for the Nck adapters in enhancing TCR signal strength, thereby fine-tuning the threshold of thymocyte selection and shaping the preimmune T cell repertoire. PMID:21078909

  18. Phenotypic flexibility of gape anatomy fine-tunes the aquatic prey-capture system of newts.

    PubMed

    Van Wassenbergh, Sam; Heiss, Egon

    2016-01-01

    A unique example of phenotypic flexibility of the oral apparatus is present in newts (Salamandridae) that seasonally change between an aquatic and a terrestrial habitat. Newts grow flaps of skin between their upper and lower jaws, the labial lobes, to partly close the corners of the mouth when they adopt an aquatic lifestyle during their breeding season. Using hydrodynamic simulations based on μCT-scans and cranial kinematics during prey-capture in the smooth newt (Lissotriton vulgaris), we showed that this phenotypic flexibility is an adaptive solution to improve aquatic feeding performance: both suction distance and suction force increase by approximately 15% due to the labial lobes. As the subsequent freeing of the corners of the mouth by resorption of the labial lobes is assumed beneficial for the terrestrial capture of prey by the tongue, this flexibility of the mouth fine-tunes the process of capturing prey throughout the seasonal switching between water and land. PMID:27383663

  19. Fine-tuning the Size and Minimizing the Noise of Solid-state Nanopores

    PubMed Central

    Beamish, Eric; Kwok, Harold; Tabard-Cossa, Vincent; Godin, Michel

    2013-01-01

    Solid-state nanopores have emerged as a versatile tool for the characterization of single biomolecules such as nucleic acids and proteins1. However, the creation of a nanopore in a thin insulating membrane remains challenging. Fabrication methods involving specialized focused electron beam systems can produce well-defined nanopores, but yield of reliable and low-noise nanopores in commercially available membranes remains low2,3 and size control is nontrivial4,5. Here, the application of high electric fields to fine-tune the size of the nanopore while ensuring optimal low-noise performance is demonstrated. These short pulses of high electric field are used to produce a pristine electrical signal and allow for enlarging of nanopores with subnanometer precision upon prolonged exposure. This method is performed in situ in an aqueous environment using standard laboratory equipment, improving the yield and reproducibility of solid-state nanopore fabrication. PMID:24300128

  20. A Solution to the Supersymmetric Fine-Tuning Problem within the MSSM

    SciTech Connect

    Kitano, Ryuichiro; Nomura, Yasunori; /UC, Berkeley /LBL, Berkeley

    2005-09-08

    Weak scale supersymmetry has a generic problem of fine-tuning in reproducing the correct scale for electroweak symmetry breaking. The problem is particularly severe in the minimal supersymmetric extension of the standard model (MSSM). We present a solution to this problem that does not require an extension of the MSSM at the weak scale. Superparticle masses are generated by a comparable mixture of moduli and anomaly mediated contributions, and the messenger scale of supersymmetry breaking is effectively lowered to the TeV region. Crucial elements for the solution are a large A term for the top squarks and a small B term for the Higgs doublets. Requiring no fine-tuning worse than 20%, we obtain rather sharp predictions on the spectrum. The gaugino masses are almost universal at the weak scale with the mass between 450 and 900 GeV. The squark and slepton masses are also nearly universal at the weak scale with the mass a factor of {radical}2 smaller than that of the gauginos. The only exception is the top squarks whose masses split from the other squark masses by about m{sub t}/{radical}2. The lightest Higgs boson mass is smaller than 120 GeV, while the ratio of the vacuum expectation values for the two Higgs doublets, tan {beta}, is larger than about 5. The lightest superparticle is the neutral Higgsino of the mass below 190 GeV, which can be dark matter of the universe. The mass of the lighter top squark can be smaller than 300 GeV, which may be relevant for Run II at the Tevatron.

  1. Improved transgene expression fine-tuning in mammalian cells using a novel transcription-translation network.

    PubMed

    Malphettes, Laetitia; Fussenegger, Martin

    2006-08-01

    Following the discovery of RNA interference (RNAi) and related phenomena, novel regulatory processes, attributable to small non-protein-coding RNAs, continue to emerge. Capitalizing on the ability of artificial short interfering RNAs (siRNAs) to trigger degradation of specific target transcripts, and thereby silence desired gene expression, we designed and characterized a generic transcription-translation network in which it is possible to fine-tune heterologous protein production by coordinated transcription and translation interventions using macrolide and tetracycline antibiotics. Integration of siRNA-specific target sequences (TAGs) into the 5' or 3' untranslated regions (5'UTR, 3'UTR) of a desired constitutive transcription unit rendered transgene-encoded protein (erythropoietin, EPO; human placental alkaline phosphatase, SEAP; human vascular endothelial growth factor 121, VEGF(121)) production in mammalian cells responsive to siRNA levels that can be fine-tuned by macrolide-adjustable RNA polymerase II- or III-dependent promoters. Coupling of such macrolide-responsive siRNA-triggered translation control with tetracycline-responsive transcription of tagged transgene mRNAs created an antibiotic-adjustable two-input transcription-translation network characterized by elimination of detectable leaky expression with no reduction in maximum protein production levels. This transcription-translation network revealed transgene mRNA depletion to be dependent on siRNA and mRNA levels and that translation control was able to eliminate basal expression inherent to current transcription control modalities. Coupled transcription-translation circuitries have the potential to lead the way towards composite artificial regulatory networks, to enable complex therapeutic interventions in future biopharmaceutical manufacturing, gene therapy and tissue engineering initiatives. PMID:16488500

  2. Natural solution to the naturalness problem: The universe does fine-tuning

    NASA Astrophysics Data System (ADS)

    Hamada, Yuta; Kawai, Hikaru; Kawana, Kiyoharu

    2015-12-01

    We propose a new mechanism to solve the fine-tuning problem. We start from a multi-local action S=sum iciSi+sum _{i,j}c_{i,j}SiSj+sum _{i,j,k}c_{i,j,k}SiSjSk+\\cdots , where the Si's are ordinary local actions. Then, the partition function of this system is given by Z=int doverrArr {λ } fbig (overrArr {λ }big )< f|Texp left (-iint 0^{+infty }dthat {H} (overrArr {λ };a_{cl}(t))right )|irangle , where overrArr {λ } represents the parameters of the system whose Hamiltonian is given by hat {H}(overrArr {λ };a_{cl}(t)), a_{cl}(t) is the radius of the universe determined by the Friedman equation, and fbig (overrArr {λ }big ), which is determined by S, is a smooth function of overrArr {λ }. If a value of overrArr {λ }, overrArr {λ }0, dominates in the integral, we can interpret that the parameters are dynamically tuned to overrArr {λ }0. We show that this indeed happens in some realistic systems. In particular, we consider the strong CP problem, the multiple point criticality principle, and the cosmological constant problem. It is interesting that these different phenomena can be explained by one mechanism.

  3. Finely tuning MOFs towards high-performance post-combustion CO2 capture materials.

    PubMed

    Wang, Qian; Bai, Junfeng; Lu, Zhiyong; Pan, Yi; You, Xiaozeng

    2016-01-11

    CO2 capture science and technology, particularly for the post-combustion CO2 capture, has become one of very important research fields, due to great concern of global warming. Metal-organic frameworks (MOFs) with a unique feature of structural fine-tunability, unlike the traditional porous solid materials, can provide many and powerful platforms to explore high-performance adsorbents for post-combustion CO2 capture. Until now, several strategies for finely tuning MOF structures have been developed, in which either the larger quadrupole moment and polarizability of CO2 are considered: metal ion change (I), functional groups attachment (II) and functional group insertion (III), vary the electronic nature of the pore surface; or targeting the smaller kinetic diameter of CO2 over N2 is focused on: framework interpenetration (IV), ligand shortening (V) and coordination site shifting (VI) contract the pore size of frameworks to improve their CO2 capture properties. In this review, from the viewpoint of synthetic materials scientists/chemists, we would like to introduce and summarize these strategies based upon recent work published by other groups and ourselves. PMID:26512792

  4. Fine Tuning of the Lactate and Diacetyl Production through Promoter Engineering in Lactococcus lactis

    PubMed Central

    Guo, Tingting; Kong, Jian; Zhang, Li; Zhang, Chenchen; Hu, Shumin

    2012-01-01

    Lactococcus lactis is a well-studied bacterium widely used in dairy fermentation and capable of producing metabolites with organoleptic and nutritional characteristics. For fine tuning of the distribution of glycolytic flux at the pyruvate branch from lactate to diacetyl and balancing the production of the two metabolites under aerobic conditions, a constitutive promoter library was constructed by randomizing the promoter sequence of the H2O-forming NADH oxidase gene in L. lactis. The library consisted of 30 promoters covering a wide range of activities from 7,000 to 380,000 relative fluorescence units using a green fluorescent protein as reporter. Eleven typical promoters of the library were selected for the constitutive expression of the H2O-forming NADH oxidase gene in L. lactis, and the NADH oxidase activity increased from 9.43 to 58.17-fold of the wild-type strain in small steps of activity change under aerobic conditions. Meanwhile, the lactate yield decreased from 21.15±0.08 mM to 9.94±0.07 mM, and the corresponding diacetyl production increased from 1.07±0.03 mM to 4.16±0.06 mM with the intracellular NADH/NAD+ ratios varying from 0.711±0.005 to 0.383±0.003. The results indicated that the reduced pyruvate to lactate flux was rerouted to the diacetyl with an almost linear flux variation via altered NADH/NAD+ ratios. Therefore, we provided a novel strategy to precisely control the pyruvate distribution for fine tuning of the lactate and diacetyl production through promoter engineering in L. lactis. Interestingly, the increased H2O-forming NADH oxidase activity led to 76.95% lower H2O2 concentration in the recombinant strain than that of the wild-type strain after 24 h of aerated cultivation. The viable cells were significantly elevated by four orders of magnitude within 28 days of storage at 4°C, suggesting that the increased enzyme activity could eliminate H2O2 accumulation and prolong cell survival. PMID:22558426

  5. Automated tuning of an eight-channel cardiac transceive array at 7 tesla using piezoelectric actuators

    PubMed Central

    Keith, Graeme A; Rodgers, Christopher T; Hess, Aaron T; Snyder, Carl J; Vaughan, J Thomas; Robson, Matthew D

    2015-01-01

    Purpose Ultra-high field (UHF) MR scanning in the body requires novel coil designs due to B1 field inhomogeneities. In the transverse electromagnetic field (TEM) design, maximum B1 transmit power can only be achieved if each individual transmit element is tuned and matched for different coil loads, which requires a considerable amount of valuable scanner time. Methods An integrated system for autotuning a multichannel parallel transmit (pTx) cardiac TEM array was devised, using piezoelectric actuators, power monitoring equipment and control software. The reproducibility and performance of the system were tested and the power responses of the coil elements were profiled. An automated optimization method was devised and evaluated. Results The time required to tune an eight-element pTx cardiac RF array was reduced from a mean of 30 min to less than 10 min with the use of this system. Conclusion Piezoelectric actuators are an attractive means of tuning RF coil arrays to yield more efficient B1 transmission into the subject. An automated mechanism for tuning these elements provides a practical solution for cardiac imaging at UHF, bringing this technology closer to clinical use. Magn Reson Med 73:2390–2397, 2015. © 2014 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. PMID:24986525

  6. Phospho-Pon Binding-Mediated Fine-Tuning of Plk1 Activity.

    PubMed

    Zhu, Kang; Shan, Zelin; Zhang, Lu; Wen, Wenyu

    2016-07-01

    In Drosophila neuroblasts (NBs), the asymmetrical localization and segregation of the cell-fate determinant Numb are regulated by its adaptor Partner of Numb (Pon) and the cell-cycle kinase Polo. Polo phosphorylates the Pon localization domain, thus leading to its basal distribution together with Numb, albeit through an unclear mechanism. Here, we find that Cdk1 phosphorylates Pon at Thr63, thus creating a docking site for the Polo-box domain (PBD) of Polo-like kinase 1 (Plk1). The crystal structure of the Plk1 PBD/phospho-Pon complex reveals that two phospho-Pon bound PBDs associate to form a dimer of dimers. We provide evidence that phospho-Pon binding-induced PBD dimerization relieves the autoinhibition of Plk1. Moreover, we demonstrate that the priming Cdk1 phosphorylation of Pon is important for sequential Plk1 phosphorylation. Our results not only provide structural insight into how phosphoprotein binding activates Plk1 but also suggest that binding to different phosphoproteins might mediate the fine-tuning of Plk1 activity. PMID:27238966

  7. Fine-tuned ATP signals are acute mediators in osteocyte mechanotransduction.

    PubMed

    Kringelbach, Tina M; Aslan, Derya; Novak, Ivana; Ellegaard, Maria; Syberg, Susanne; Andersen, Christina K B; Kristiansen, Kim A; Vang, Ole; Schwarz, Peter; Jørgensen, Niklas R

    2015-12-01

    Osteocytes are considered the primary mechanosensors of bone, but the signaling pathways they apply in mechanotransduction are still incompletely investigated and characterized. A growing body of data strongly indicates that P2 receptor signaling among osteoblasts and osteoclasts has regulatory effects on bone remodeling. Therefore, we hypothesized that ATP signaling is also applied by osteocytes in mechanotransduction. We applied a short fluid pulse on MLO-Y4 osteocyte-like cells during real-time detection of ATP and demonstrated that mechanical stimulation activates the acute release of ATP and that these acute ATP signals are fine-tuned according to the magnitude of loading. ATP release was then challenged by pharmacological inhibitors, which indicated a vesicular release pathway for acute ATP signals. Finally, we showed that osteocytes express functional P2X2 and P2X7 receptors and respond to even low concentrations of nucleotides by increasing intracellular calcium concentration. These results indicate that in osteocytes, vesicular ATP release is an acute mediator of mechanical signals and the magnitude of loading. These and previous results, therefore, implicate purinergic signaling as an early signaling pathway in osteocyte mechanotransduction. PMID:26327582

  8. Statistical-Mechanical Analysis of Pre-training and Fine Tuning in Deep Learning

    NASA Astrophysics Data System (ADS)

    Ohzeki, Masayuki

    2015-03-01

    In this paper, we present a statistical-mechanical analysis of deep learning. We elucidate some of the essential components of deep learning — pre-training by unsupervised learning and fine tuning by supervised learning. We formulate the extraction of features from the training data as a margin criterion in a high-dimensional feature-vector space. The self-organized classifier is then supplied with small amounts of labelled data, as in deep learning. Although we employ a simple single-layer perceptron model, rather than directly analyzing a multi-layer neural network, we find a nontrivial phase transition that is dependent on the number of unlabelled data in the generalization error of the resultant classifier. In this sense, we evaluate the efficacy of the unsupervised learning component of deep learning. The analysis is performed by the replica method, which is a sophisticated tool in statistical mechanics. We validate our result in the manner of deep learning, using a simple iterative algorithm to learn the weight vector on the basis of belief propagation.

  9. Fibroblast Growth Factor 21 Protects against Atherosclerosis via Fine-Tuning the Multiorgan Crosstalk.

    PubMed

    Jin, Leigang; Lin, Zhuofeng; Xu, Aimin

    2016-02-01

    Fibroblast growth factor 21 (FGF21) is a metabolic hormone with pleiotropic effects on energy metabolism and insulin sensitivity. Besides its antiobese and antidiabetic activity, FGF21 also possesses the protective effects against atherosclerosis. Circulating levels of FGF21 are elevated in patients with atherosclerosis, macrovascular and microvascular complications of diabetes, possibly due to a compensatory upregulation. In apolipoprotein E-deficient mice, formation of atherosclerotic plaques is exacerbated by genetic depletion of FGF21, but is attenuated upon replenishment with recombinant FGF21. However, the blood vessel is not the direct target of FGF21, and the antiatherosclerotic activity of FGF21 is attributed to its actions in adipose tissues and liver. In adipocytes, FGF21 promotes secretion of adiponectin, which in turn acts directly on blood vessels to reduce endothelial dysfunction, inhibit proliferation of smooth muscle cells and block conversion of macrophages to foam cells. Furthermore, FGF21 suppresses cholesterol biosynthesis and attenuates hypercholesterolemia by inhibiting the transcription factor sterol regulatory element-binding protein-2 in hepatocytes. The effects of FGF21 on elevation of adiponectin and reduction of hypercholesterolemia are also observed in a phase-1b clinical trial in patients with obesity and diabetes. Therefore, FGF21 exerts its protection against atherosclerosis by fine-tuning the interorgan crosstalk between liver, brain, adipose tissue, and blood vessels. PMID:26912152

  10. Redirecting abiraterone metabolism to fine-tune prostate cancer anti-androgen therapy.

    PubMed

    Li, Zhenfei; Alyamani, Mohammad; Li, Jianneng; Rogacki, Kevin; Abazeed, Mohamed; Upadhyay, Sunil K; Balk, Steven P; Taplin, Mary-Ellen; Auchus, Richard J; Sharifi, Nima

    2016-05-26

    Abiraterone blocks androgen synthesis and prolongs survival in patients with castration-resistant prostate cancer, which is otherwise driven by intratumoral androgen synthesis. Abiraterone is metabolized in patients to Δ(4)-abiraterone (D4A), which has even greater anti-tumour activity and is structurally similar to endogenous steroidal 5α-reductase substrates, such as testosterone. Here, we show that D4A is converted to at least three 5α-reduced and three 5β-reduced metabolites in human serum. The initial 5α-reduced metabolite, 3-keto-5α-abiraterone, is present at higher concentrations than D4A in patients with prostate cancer taking abiraterone, and is an androgen receptor agonist, which promotes prostate cancer progression. In a clinical trial of abiraterone alone, followed by abiraterone plus dutasteride (a 5α-reductase inhibitor), 3-keto-5α-abiraterone and downstream metabolites were depleted by the addition of dutasteride, while D4A concentrations rose, showing that dutasteride effectively blocks production of a tumour-promoting metabolite and permits D4A accumulation. Furthermore, dutasteride did not deplete the three 5β-reduced metabolites, which were also clinically detectable, demonstrating the specific biochemical effects of pharmacological 5α-reductase inhibition on abiraterone metabolism. Our findings suggest a previously unappreciated and biochemically specific method of clinically fine-tuning abiraterone metabolism to optimize therapy. PMID:27225130

  11. Metalloprotease OMA1 Fine-tunes Mitochondrial Bioenergetic Function and Respiratory Supercomplex Stability.

    PubMed

    Bohovych, Iryna; Fernandez, Mario R; Rahn, Jennifer J; Stackley, Krista D; Bestman, Jennifer E; Anandhan, Annadurai; Franco, Rodrigo; Claypool, Steven M; Lewis, Robert E; Chan, Sherine S L; Khalimonchuk, Oleh

    2015-01-01

    Mitochondria are involved in key cellular functions including energy production, metabolic homeostasis, and apoptosis. Normal mitochondrial function is preserved by several interrelated mechanisms. One mechanism - intramitochondrial quality control (IMQC) - is represented by conserved proteases distributed across mitochondrial compartments. Many aspects and physiological roles of IMQC components remain unclear. Here, we show that the IMQC protease Oma1 is required for the stability of the respiratory supercomplexes and thus balanced and tunable bioenergetic function. Loss of Oma1 activity leads to a specific destabilization of respiratory supercomplexes and consequently to unbalanced respiration and progressive respiratory decline in yeast. Similarly, experiments in cultured Oma1-deficient mouse embryonic fibroblasts link together impeded supercomplex stability and inability to maintain proper respiration under conditions that require maximal bioenergetic output. Finally, transient knockdown of OMA1 in zebrafish leads to impeded bioenergetics and morphological defects of the heart and eyes. Together, our biochemical and genetic studies in yeast, zebrafish and mammalian cells identify a novel and conserved physiological role for Oma1 protease in fine-tuning of respiratory function. We suggest that this unexpected physiological role is important for cellular bioenergetic plasticity and may contribute to Oma1-associated disease phenotypes in humans. PMID:26365306

  12. Tuning Piezo ion channels to detect molecular-scale movements relevant for fine touch

    PubMed Central

    Poole, Kate; Herget, Regina; Lapatsina, Liudmila; Ngo, Ha-Duong; Lewin, Gary R.

    2014-01-01

    In sensory neurons, mechanotransduction is sensitive, fast and requires mechanosensitive ion channels. Here we develop a new method to directly monitor mechanotransduction at defined regions of the cell-substrate interface. We show that molecular-scale (~13 nm) displacements are sufficient to gate mechanosensitive currents in mouse touch receptors. Using neurons from knockout mice, we show that displacement thresholds increase by one order of magnitude in the absence of stomatin-like protein 3 (STOML3). Piezo1 is the founding member of a class of mammalian stretch-activated ion channels, and we show that STOML3, but not other stomatin-domain proteins, brings the activation threshold for Piezo1 and Piezo2 currents down to ~10 nm. Structure–function experiments localize the Piezo modulatory activity of STOML3 to the stomatin domain, and higher-order scaffolds are a prerequisite for function. STOML3 is the first potent modulator of Piezo channels that tunes the sensitivity of mechanically gated channels to detect molecular-scale stimuli relevant for fine touch. PMID:24662763

  13. Fine-tuning the ubiquitin code at DNA double-strand breaks: deubiquitinating enzymes at work

    PubMed Central

    Citterio, Elisabetta

    2015-01-01

    Ubiquitination is a reversible protein modification broadly implicated in cellular functions. Signaling processes mediated by ubiquitin (ub) are crucial for the cellular response to DNA double-strand breaks (DSBs), one of the most dangerous types of DNA lesions. In particular, the DSB response critically relies on active ubiquitination by the RNF8 and RNF168 ub ligases at the chromatin, which is essential for proper DSB signaling and repair. How this pathway is fine-tuned and what the functional consequences are of its deregulation for genome integrity and tissue homeostasis are subject of intense investigation. One important regulatory mechanism is by reversal of substrate ubiquitination through the activity of specific deubiquitinating enzymes (DUBs), as supported by the implication of a growing number of DUBs in DNA damage response processes. Here, we discuss the current knowledge of how ub-mediated signaling at DSBs is controlled by DUBs, with main focus on DUBs targeting histone H2A and on their recent implication in stem cell biology and cancer. PMID:26442100

  14. Fine-tuning of eTRPM8 expression and activity conditions keratinocyte fate.

    PubMed

    Bidaux, Gabriel; Borowiec, Anne-Sophie; Prevarskaya, Natalia; Gordienko, Dmitri

    2016-07-01

    Recently, we reported the cloning and characterization of short isoform of the icilin-activated cold receptor TRPM8 channel in keratinocytes, dubbed eTRPM8. We demonstrated that eTRPM8 via fine tuning of the endoplasmic reticulum (ER) - mitochondria Ca(2+) shuttling regulates mitochondrial ATP and superoxide (O2(•-)) production and, thereby, mediates control of epidermal homeostasis by mild cold. Here, we provide additional information explaining why eTRPM8 suppression and TRPM8 stimulation both inhibit keratinocyte growth. We also demonstrate that stimulation of eTRPM8 with icilin may give rise to sustained oscillatory responses. Furthermore, we show that ATP-induced cytosolic and mitochondrial Ca(2+) responses are attenuated by eTRPM8 suppression. This suggests positive interplay between eTRPM8 and purinergic signaling pathways, what may serve to facilitate the ER-mitochondria Ca(2+) shuttling. Finally, we demonstrate that cold (25°C) induces eTRPM8-dependent superoxide-mediated necrosis of keratinocytes. Altogether, these results are in line with our model of eTRPM8-mediated cold-dependent balance between keratinocyte proliferation and differentiation. PMID:27014839

  15. Fine Tuning of the UPR by the Ubiquitin Ligases Siah1/2

    PubMed Central

    Scortegagna, Marzia; Kim, Hyungsoo; Li, Jian-Liang; Yao, Hang; Brill, Laurence M.; Han, Jaeseok; Lau, Eric; Bowtell, David; Haddad, Gabriel; Kaufman, Randal J.; Ronai, Ze'ev A.

    2014-01-01

    The endoplasmic reticulum (ER) responds to changes in intracellular homeostasis through activation of the unfolded protein response (UPR). Yet, it is not known how UPR-signaling coordinates adaptation versus cell death. Previous studies suggested that signaling through PERK/ATF4 is required for cell death. We show that high levels of ER stress (i.e., ischemia-like conditions) induce transcription of the ubiquitin ligases Siah1/2 through the UPR transducers PERK/ATF4 and IRE1/sXBP1. In turn, Siah1/2 attenuates proline hydroxylation of ATF4, resulting in its stabilization, thereby augmenting ER stress output. Conversely, ATF4 activation is reduced upon Siah1/2 KD in cultured cells, which attenuates ER stress-induced cell death. Notably, Siah1a+/−::Siah2−/− mice subjected to neuronal ischemia exhibited smaller infarct volume and were protected from ischemia-induced death, compared with the wild type (WT) mice. In all, Siah1/2 constitutes an obligatory fine-tuning mechanism that predisposes cells to death under severe ER stress conditions. PMID:24809345

  16. Tissue-Specific Regulation of Gibberellin Signaling Fine-Tunes Arabidopsis Iron-Deficiency Responses.

    PubMed

    Wild, Michael; Davière, Jean-Michel; Regnault, Thomas; Sakvarelidze-Achard, Lali; Carrera, Esther; Lopez Diaz, Isabel; Cayrel, Anne; Dubeaux, Guillaume; Vert, Grégory; Achard, Patrick

    2016-04-18

    Iron is an essential element for most living organisms. Plants acquire iron from the rhizosphere and have evolved different biochemical and developmental responses to adapt to a low-iron environment. In Arabidopsis, FIT encodes a basic helix-loop-helix transcription factor that activates the expression of iron-uptake genes in root epidermis upon iron deficiency. Here, we report that the gibberellin (GA)-signaling DELLA repressors contribute substantially in the adaptive responses to iron-deficient conditions. When iron availability decreases, DELLAs accumulate in the root meristem, thereby restraining root growth, while being progressively excluded from epidermal cells in the root differentiation zone. Such DELLA exclusion from the site of iron acquisition relieves FIT from DELLA-dependent inhibition and therefore promotes iron uptake. Consistent with this mechanism, expression of a non-GA-degradable DELLA mutant protein in root epidermis interferes with iron acquisition. Hence, spatial distribution of DELLAs in roots is essential to fine-tune the adaptive responses to iron availability. PMID:27093087

  17. Fine-tuning somatostatin receptor signalling by agonist-selective phosphorylation and dephosphorylation: IUPHAR Review 5

    PubMed Central

    Schulz, Stefan; Lehmann, Andreas; Kliewer, Andrea; Nagel, Falko

    2014-01-01

    The biological actions of somatostatin are mediated by a family of five GPCRs, named sst1 to sst5. Somatostatin receptors exhibit equally high-binding affinities to their natural ligand somatostatin-14 and largely overlapping distributions. The overexpression of somatostatin receptors in human tumours is the molecular basis for diagnostic and therapeutic application of the stable somatostatin analogues octreotide, lanreotide and pasireotide. The efficiency of somatostatin receptor signalling is tightly regulated and ultimately limited by the coordinated phosphorylation and dephosphorylation of intracellular carboxyl-terminal serine and threonine residues. Here, we review and discuss recent progress in the generation and application of phosphosite-specific antibodies for human sst2 and sst5 receptors. These phosphosite-specific antibodies are unique tools to monitor the spatial and temporal dynamics of receptors phosphorylation and dephosphorylation. Using a combined approach of phosphosite-specific antibodies and siRNA knock-down screening, relevant kinases and phosphatases were identified. Emerging evidence suggests distinct mechanisms of agonist-selective fine-tuning for individual somatostatin receptors. The recently uncovered differences in phosphorylation and dephosphorylation of these receptors may hence be of physiological significance in mediating responses to acute, persistent or repeated stimuli in a variety of target tissues. PMID:24328848

  18. Fine tuning the correlation limit of spatio-temporal signal space separation for magnetoencephalography.

    PubMed

    Medvedovsky, Mordekhay; Taulu, Samu; Bikmullina, Rozaliya; Ahonen, Antti; Paetau, Ritva

    2009-02-15

    Head, jaw and tongue movements contribute to speech artifacts in magnetoencephalography (MEG). Their sources lay close to MEG sensors, therefore, the spatio-temporal signal space separation method (tSSS), specifically suppressing nearby artifacts, can be used for speech artifact suppression. After data reconstruction by signal space separation (referred as SSS), tSSS identifies artifacts by their correlated temporal behavior inside and outside the sensor helmet. The artifacts to be eliminated are thresholded by the quantitative level of this correlation determined by correlation limit (CL). Unnecessarily high CL value may result in suboptimal interference suppression. We evaluated the performance of tSSS with different CLs on MEG data containing speech artifacts. MEG was recorded with 204 planar gradiometers and 102 magnetometers in two subjects counting aloud. The recorded data were processed by tSSS using CLs 0.98, 0.8 and 0.6, and traces were compared. The speech artifact was increasingly suppressed with decreasing CL, but sufficient suppression was achieved at different CL in each subject. Alpha rhythm was not suppressed with CL 0.98 or 0.8; some amplitude reduction with CL 0.6 occurred in one subject. The tSSS is a robust tool suppressing MEG artifacts. It can be fine tuned for challenging artifacts which, after insufficient rejection might resemble brain signals. PMID:18996412

  19. Fine-tuned PEGylation of chitosan to maintain optimal siRNA-nanoplex bioactivity.

    PubMed

    Guţoaia, Andra; Schuster, Liane; Margutti, Simona; Laufer, Stefan; Schlosshauer, Burkhard; Krastev, Rumen; Stoll, Dieter; Hartmann, Hanna

    2016-06-01

    Polyethylene glycol (PEG) is a widely used modification for drug delivery systems. It reduces undesired interaction with biological components, aggregation of complexes and serves as a hydrophilic linker of ligands for targeted drug delivery. However, PEGylation can also lead to undesired changes in physicochemical characteristics of chitosan/siRNA nanoplexes and hamper gene silencing. To address this conflicting issue, PEG-chitosan copolymers were synthesized with stepwise increasing degrees of PEG substitution (1.5% to 8.0%). Subsequently formed PEG-chitosan/siRNA nanoplexes were characterized physicochemically and biologically. The results showed that small ratios of chitosan PEGylation did not affect nanoplex stability and density. However, higher PEGylation ratios reduced nanoplex size and charge, as well as cell uptake and final siRNA knockdown efficiency. Therefore, we recommend fine-tuning of PEGylation ratios to generate PEG-chitosan/siRNA delivery systems with maximum bioactivity. The degree of PEGylation for chitosan/siRNA nanoplexes should be kept low in order to maintain optimal nanoplex efficiency. PMID:27083340

  20. Metalloprotease OMA1 Fine-tunes Mitochondrial Bioenergetic Function and Respiratory Supercomplex Stability

    PubMed Central

    Bohovych, Iryna; Fernandez, Mario R.; Rahn, Jennifer J.; Stackley, Krista D.; Bestman, Jennifer E.; Anandhan, Annadurai; Franco, Rodrigo; Claypool, Steven M.; Lewis, Robert E.; Chan, Sherine S. L.; Khalimonchuk, Oleh

    2015-01-01

    Mitochondria are involved in key cellular functions including energy production, metabolic homeostasis, and apoptosis. Normal mitochondrial function is preserved by several interrelated mechanisms. One mechanism – intramitochondrial quality control (IMQC) – is represented by conserved proteases distributed across mitochondrial compartments. Many aspects and physiological roles of IMQC components remain unclear. Here, we show that the IMQC protease Oma1 is required for the stability of the respiratory supercomplexes and thus balanced and tunable bioenergetic function. Loss of Oma1 activity leads to a specific destabilization of respiratory supercomplexes and consequently to unbalanced respiration and progressive respiratory decline in yeast. Similarly, experiments in cultured Oma1-deficient mouse embryonic fibroblasts link together impeded supercomplex stability and inability to maintain proper respiration under conditions that require maximal bioenergetic output. Finally, transient knockdown of OMA1 in zebrafish leads to impeded bioenergetics and morphological defects of the heart and eyes. Together, our biochemical and genetic studies in yeast, zebrafish and mammalian cells identify a novel and conserved physiological role for Oma1 protease in fine-tuning of respiratory function. We suggest that this unexpected physiological role is important for cellular bioenergetic plasticity and may contribute to Oma1-associated disease phenotypes in humans. PMID:26365306

  1. Core formation in dwarf haloes with self-interacting dark matter: no fine-tuning necessary

    NASA Astrophysics Data System (ADS)

    Elbert, Oliver D.; Bullock, James S.; Garrison-Kimmel, Shea; Rocha, Miguel; Oñorbe, Jose; Peter, Annika H. G.

    2015-10-01

    We investigate the effect of self-interacting dark matter (SIDM) on the density profiles of Vmax ≃ 40km s-1 isolated dwarf dark matter haloes - the scale of relevance for the too big to fail problem (TBTF) - using very high resolution cosmological zoom simulations. Each halo has millions of particles within its virial radius. We find that SIDM models with cross-sections per unit mass spanning the range σ/m = 0.5-50 cm2 g-1 alleviate TBTF and produce constant-density cores of size 300-1000 pc, comparable to the half-light radii of M⋆ ˜ 105 - 7 M⊙ dwarfs. The largest, lowest density cores develop for cross-sections in the middle of this range, σ/m ˜ 5-10 cm2 g-1. Our largest SIDM cross-section run (σ/m = 50 cm2 g-1) develops a slightly denser core owing to mild core-collapse behaviour, but it remains less dense than the cold dark matter case and retains a constant-density core profile. Our work suggests that SIDM cross-sections as large or larger than 50 cm2 g-1 remain viable on velocity scales of dwarf galaxies (vrms ˜ 40 km s-1). The range of SIDM cross-sections that alleviate TBTF and the cusp/core problem spans at least two orders of magnitude and therefore need not be particularly fine-tuned.

  2. Fibroblast Growth Factor 21 Protects against Atherosclerosis via Fine-Tuning the Multiorgan Crosstalk

    PubMed Central

    Jin, Leigang; Lin, Zhuofeng

    2016-01-01

    Fibroblast growth factor 21 (FGF21) is a metabolic hormone with pleiotropic effects on energy metabolism and insulin sensitivity. Besides its antiobese and antidiabetic activity, FGF21 also possesses the protective effects against atherosclerosis. Circulating levels of FGF21 are elevated in patients with atherosclerosis, macrovascular and microvascular complications of diabetes, possibly due to a compensatory upregulation. In apolipoprotein E-deficient mice, formation of atherosclerotic plaques is exacerbated by genetic depletion of FGF21, but is attenuated upon replenishment with recombinant FGF21. However, the blood vessel is not the direct target of FGF21, and the antiatherosclerotic activity of FGF21 is attributed to its actions in adipose tissues and liver. In adipocytes, FGF21 promotes secretion of adiponectin, which in turn acts directly on blood vessels to reduce endothelial dysfunction, inhibit proliferation of smooth muscle cells and block conversion of macrophages to foam cells. Furthermore, FGF21 suppresses cholesterol biosynthesis and attenuates hypercholesterolemia by inhibiting the transcription factor sterol regulatory element-binding protein-2 in hepatocytes. The effects of FGF21 on elevation of adiponectin and reduction of hypercholesterolemia are also observed in a phase-1b clinical trial in patients with obesity and diabetes. Therefore, FGF21 exerts its protection against atherosclerosis by fine-tuning the interorgan crosstalk between liver, brain, adipose tissue, and blood vessels. PMID:26912152

  3. Community-integrated omics links dominance of a microbial generalist to fine-tuned resource usage

    PubMed Central

    Muller, Emilie E. L.; Pinel, Nicolás; Laczny, Cédric C.; Hoopmann, Michael R.; Narayanasamy, Shaman; Lebrun, Laura A.; Roume, Hugo; Lin, Jake; May, Patrick; Hicks, Nathan D.; Heintz-Buschart, Anna; Wampach, Linda; Liu, Cindy M.; Price, Lance B.; Gillece, John D.; Guignard, Cédric; Schupp, James M.; Vlassis, Nikos; Baliga, Nitin S.; Moritz, Robert L.; Keim, Paul S.; Wilmes, Paul

    2014-01-01

    Microbial communities are complex and dynamic systems that are primarily structured according to their members’ ecological niches. To investigate how niche breadth (generalist versus specialist lifestyle strategies) relates to ecological success, we develop and apply an integrative workflow for the multi-omic analysis of oleaginous mixed microbial communities from a biological wastewater treatment plant. Time- and space-resolved coupled metabolomic and taxonomic analyses demonstrate that the community-wide lipid accumulation phenotype is associated with the dominance of the generalist bacterium Candidatus Microthrix spp. By integrating population-level genomic reconstructions (reflecting fundamental niches) with transcriptomic and proteomic data (realised niches), we identify finely tuned gene expression governing resource usage by Candidatus Microthrix parvicella over time. Moreover, our results indicate that the fluctuating environmental conditions constrain the accumulation of genetic variation in Candidatus Microthrix parvicella likely due to fitness trade-offs. Based on our observations, niche breadth has to be considered as an important factor for understanding the evolutionary processes governing (microbial) population sizes and structures in situ. PMID:25424998

  4. Dendrites are dispensable for basic motoneuron function but essential for fine tuning of behavior

    PubMed Central

    Ryglewski, Stefanie; Kadas, Dimitrios; Hutchinson, Katie; Schuetzler, Natalie; Vonhoff, Fernando; Duch, Carsten

    2014-01-01

    Dendrites are highly complex 3D structures that define neuronal morphology and connectivity and are the predominant sites for synaptic input. Defects in dendritic structure are highly consistent correlates of brain diseases. However, the precise consequences of dendritic structure defects for neuronal function and behavioral performance remain unknown. Here we probe dendritic function by using genetic tools to selectively abolish dendrites in identified Drosophila wing motoneurons without affecting other neuronal properties. We find that these motoneuron dendrites are unexpectedly dispensable for synaptic targeting, qualitatively normal neuronal activity patterns during behavior, and basic behavioral performance. However, significant performance deficits in sophisticated motor behaviors, such as flight altitude control and switching between discrete courtship song elements, scale with the degree of dendritic defect. To our knowledge, our observations provide the first direct evidence that complex dendrite architecture is critically required for fine-tuning and adaptability within robust, evolutionarily constrained behavioral programs that are vital for mating success and survival. We speculate that the observed scaling of performance deficits with the degree of structural defect is consistent with gradual increases in intellectual disability during continuously advancing structural deficiencies in progressive neurological disorders. PMID:25453076

  5. Graphene-based fine-tunable optical delay line for optical beamforming in phased-array antennas.

    PubMed

    Tatoli, Teresa; Conteduca, Donato; Dell'Olio, Francesco; Ciminelli, Caterina; Armenise, Mario N

    2016-06-01

    The design of an integrated graphene-based fine-tunable optical delay line on silicon nitride for optical beamforming in phased-array antennas is reported. A high value of the optical delay time (τg=920  ps) together with a compact footprint (4.15  mm2) and optical loss <27  dB make this device particularly suitable for highly efficient steering in active phased-array antennas. The delay line includes two graphene-based Mach-Zehnder interferometer switches and two vertically stacked microring resonators between which a graphene capacitor is placed. The tuning range is obtained by varying the value of the voltage applied to the graphene electrodes, which controls the optical path of the light propagation and therefore the delay time. The graphene provides a faster reconfigurable time and low values of energy dissipation. Such significant advantages, together with a negligible beam-squint effect, allow us to overcome the limitations of conventional RF beamformers. A highly efficient fine-tunable optical delay line for the beamsteering of 20 radiating elements up to ±20° in the azimuth direction of a tile in a phased-array antenna of an X-band synthetic aperture radar has been designed. PMID:27411185

  6. Photoassisted photoluminescence fine-tuning of gold nanodots through free radical-mediated ligand-assembly

    NASA Astrophysics Data System (ADS)

    Tseng, Yu-Ting; Cherng, Rochelle; Harroun, Scott G.; Yuan, Zhiqin; Lin, Tai-Yuan; Wu, Chien-Wei; Chang, Huan-Tsung; Huang, Chih-Ching

    2016-05-01

    In this study, we have developed a simple photoassisted ligand assembly to fine-tune the photoluminescence (PL) of (11-mercaptoundecyl)-N,N,N-trimethylammonium bromide-capped gold nanodots (11-MUTAB-Au NDs). The 11-MUTAB-Au NDs (size: ca. 1.8 nm), obtained from the reaction of gold nanoparticles (ca. 3 nm) and 11-MUTAB, exhibited weak, near-infrared (NIR) PL at 700 nm with a quantum yield (QY) of 0.37% upon excitation at 365 nm. The PL QY of the Au NDs increased to 11.43% after reaction with 11-mercaptoundecanoic acid (11-MUA) for 30 min under ultraviolet (UV) light, which was accompanied by a PL wavelength shift to the green region (~520 nm). UV-light irradiation accelerates 11-MUA assembly on the 11-MUTABAu NDs (11-MUA/11-MUTAB-Au NDs) through a radical-mediated reaction. Furthermore, the PL wavelength of the 11-MUA/11-MUTAB-Au NDs can be switched to 640 nm via cysteamine under UV-light irradiation. We propose that the PL of the Au NDs with NIR and visible emissions was originally from the surface thiol-Au complexes and the Au core, respectively. These dramatically different optical properties of the Au NDs were due to variation in the surface ligands, as well as the densities and surface oxidant states of the surface Au atoms/ions. These effects can be controlled by assembling surface thiol ligands and accelerated by UV irradiation.In this study, we have developed a simple photoassisted ligand assembly to fine-tune the photoluminescence (PL) of (11-mercaptoundecyl)-N,N,N-trimethylammonium bromide-capped gold nanodots (11-MUTAB-Au NDs). The 11-MUTAB-Au NDs (size: ca. 1.8 nm), obtained from the reaction of gold nanoparticles (ca. 3 nm) and 11-MUTAB, exhibited weak, near-infrared (NIR) PL at 700 nm with a quantum yield (QY) of 0.37% upon excitation at 365 nm. The PL QY of the Au NDs increased to 11.43% after reaction with 11-mercaptoundecanoic acid (11-MUA) for 30 min under ultraviolet (UV) light, which was accompanied by a PL wavelength shift to the green region

  7. Leaf color is fine-tuned on the solar spectra to avoid strand direct solar radiation.

    PubMed

    Kume, Atsushi; Akitsu, Tomoko; Nasahara, Kenlo Nishida

    2016-07-01

    The spectral distributions of light absorption rates by intact leaves are notably different from the incident solar radiation spectra, for reasons that remain elusive. Incident global radiation comprises two main components; direct radiation from the direction of the sun, and diffuse radiation, which is sunlight scattered by molecules, aerosols and clouds. Both irradiance and photon flux density spectra differ between direct and diffuse radiation in their magnitude and profile. However, most research has assumed that the spectra of photosynthetically active radiation (PAR) can be averaged, without considering the radiation classes. We used paired spectroradiometers to sample direct and diffuse solar radiation, and obtained relationships between the PAR spectra and the absorption spectra of photosynthetic pigments and organs. As monomers in solvent, the spectral absorbance of Chl a decreased with the increased spectral irradiance (W m(-2) nm(-1)) of global PAR at noon (R(2) = 0.76), and was suitable to avoid strong spectral irradiance (λmax = 480 nm) rather than absorb photon flux density (μmol m(-2) s(-1) nm(-1)) efficiently. The spectral absorption of photosystems and the intact thallus and leaves decreased linearly with the increased spectral irradiance of direct PAR at noon (I dir-max), where the wavelength was within the 450-650 nm range (R(2) = 0.81). The higher-order structure of photosystems systematically avoided the strong spectral irradiance of I dir-max. However, when whole leaves were considered, leaf anatomical structure and light scattering in leaf tissues made the leaves grey bodies for PAR and enabled high PAR use efficiency. Terrestrial green plants are fine-tuned to spectral dynamics of incident solar radiation and PAR absorption is increased in various structural hierarchies. PMID:26943164

  8. A versatile apparatus for the fine-tuned synthesis of cluster-based materials.

    PubMed

    Fischer, A; Kruk, R; Hahn, H

    2015-02-01

    In this paper, a custom-designed experimental setup for the fine-tuned synthesis of various cluster-based materials is presented. Providing custom-designed deposition stages and special sample holders it offers a high degree of control over the sample characteristics such as the cluster size, cluster amounts, and sample homogeneity in combination with high sample purity. The system is capable of producing thin films of pure clusters and various cluster-matrix combinations with cluster sizes ranging from single atoms up to aggregates of several thousand atoms. Two custom-designed deposition stages are available, one utilizes the full cluster beam, yielding micrograms of pure clusters within a few hours and the second one uses mass-separated clusters (mass-resolution between 2% and 10%), yielding nanograms of pure clusters in the same timescale. Furthermore, at the second deposition stage, a variety of matrix materials can be co-deposited at a controlled sample temperature between 153 K and 673 K. In order to prove the capabilities of the apparatus, a series of experiments with Fe clusters embedded in Ag matrices with different volume fractions of clusters were carried out. Energy dispersive X-ray spectroscopy measurements revealed that the amount of deposited clusters as well as the sample homogeneity can be controlled with an outstanding accuracy of 10%. Additional measurements of the magnetic properties indicated the presence of separated clusters for volume fractions of clusters around 2 volume percent (vol. %), while above this concentration (10 vol. %) a partial aggregation of the clusters was observed. It was also shown that the resulting thin films are nearly oxygen free, which ascertains that oxygen sensitive materials can be safely handled in this newly developed apparatus. PMID:25725833

  9. Conformational Fine-Tuning of Pore-Forming Peptide Potency and Selectivity.

    PubMed

    Krauson, Aram J; Hall, O Morgan; Fuselier, Taylor; Starr, Charles G; Kauffman, W Berkeley; Wimley, William C

    2015-12-30

    To better understand the sequence-structure-function relationships that control the activity and selectivity of membrane-permeabilizing peptides, we screened a peptide library, based on the archetypal pore-former melittin, for loss-of-function variants. This was accomplished by assaying library members for failure to cause leakage of entrapped contents from synthetic lipid vesicles at a peptide-to-lipid ratio of 1:20, 10-fold higher than the concentration at which melittin efficiently permeabilizes the same vesicles. Surprisingly, about one-third of the library members are inactive under these conditions. In the negative peptides, two changes of hydrophobic residues to glycine were especially abundant. We show that loss-of-function activity can be completely recapitulated by a single-residue change of the leucine at position 16 to glycine. Unlike the potently cytolytic melittin, the loss-of-function peptides, including the single-site variant, are essentially inactive against phosphatidylcholine vesicles and multiple types of eukaryotic cells. Loss of function is shown to result from a shift in the binding-folding equilibrium away from the active, bound, α-helical state toward the inactive, unbound, random-coil state. Accordingly, the addition of anionic lipids to synthetic lipid vesicles restored binding, α-helical secondary structure, and potent activity of the "negative" peptides. While nontoxic to mammalian cells, the single-site variant has potent bactericidal activity, consistent with the anionic nature of bacterial membranes. The results show that conformational fine-tuning of helical pore-forming peptides is a powerful way to modulate their activity and selectivity. PMID:26632653

  10. Conformational Fine-Tuning of Pore-Forming Peptide Potency and Selectivity

    PubMed Central

    2015-01-01

    To better understand the sequence–structure–function relationships that control the activity and selectivity of membrane-permeabilizing peptides, we screened a peptide library, based on the archetypal pore-former melittin, for loss-of-function variants. This was accomplished by assaying library members for failure to cause leakage of entrapped contents from synthetic lipid vesicles at a peptide-to-lipid ratio of 1:20, 10-fold higher than the concentration at which melittin efficiently permeabilizes the same vesicles. Surprisingly, about one-third of the library members are inactive under these conditions. In the negative peptides, two changes of hydrophobic residues to glycine were especially abundant. We show that loss-of-function activity can be completely recapitulated by a single-residue change of the leucine at position 16 to glycine. Unlike the potently cytolytic melittin, the loss-of-function peptides, including the single-site variant, are essentially inactive against phosphatidylcholine vesicles and multiple types of eukaryotic cells. Loss of function is shown to result from a shift in the binding–folding equilibrium away from the active, bound, α-helical state toward the inactive, unbound, random-coil state. Accordingly, the addition of anionic lipids to synthetic lipid vesicles restored binding, α-helical secondary structure, and potent activity of the “negative” peptides. While nontoxic to mammalian cells, the single-site variant has potent bactericidal activity, consistent with the anionic nature of bacterial membranes. The results show that conformational fine-tuning of helical pore-forming peptides is a powerful way to modulate their activity and selectivity. PMID:26632653

  11. Fine-Tuning of Pten Localization and Phosphatase Activity Is Essential for Zebrafish Angiogenesis

    PubMed Central

    Stumpf, Miriam; Blokzijl-Franke, Sasja; den Hertog, Jeroen

    2016-01-01

    The lipid- and protein phosphatase PTEN is an essential tumor suppressor that is highly conserved among all higher eukaryotes. As an antagonist of the PI3K/Akt cell survival and proliferation pathway, it exerts its most prominent function at the cell membrane, but (PIP3-independent) functions of nuclear PTEN have been discovered as well. PTEN subcellular localization is tightly controlled by its protein conformation. In the closed conformation, PTEN localizes predominantly to the cytoplasm. Opening up of the conformation of PTEN exposes N-terminal and C-terminal regions of the protein that are required for both interaction with the cell membrane and translocation to the nucleus. Lack of Pten leads to hyperbranching of the intersegmental vessels during zebrafish embryogenesis, which is rescued by expression of exogenous Pten. Here, we observed that expression of mutant PTEN with an open conformation rescued the hyperbranching phenotype in pten double homozygous embryos and suppressed the increased p-Akt levels that are characteristic for embryos lacking Pten. In addition, in pten mutant and wild type embryos alike, open conformation PTEN induced stalled intersegmental vessels, which fail to connect with the dorsal longitudinal anastomotic vessel. Functional hyperactivity of open conformation PTEN in comparison to wild type PTEN seems to result predominantly from its enhanced recruitment to the cell membrane. Enhanced recruitment of phosphatase inactive mutants to the membrane did not induce the stalled vessel phenotype nor did it rescue the hyperbranching phenotype in pten double homozygous embryos, indicating that PTEN phosphatase activity is indispensable for its regulatory function during angiogenesis. Taken together, our data suggest that PTEN phosphatase activity needs to be carefully fine-tuned for normal embryogenesis and that the control of its subcellular localization is a key mechanism in this process. PMID:27138341

  12. A versatile apparatus for the fine-tuned synthesis of cluster-based materials

    SciTech Connect

    Fischer, A. Kruk, R.; Hahn, H.

    2015-02-15

    In this paper, a custom-designed experimental setup for the fine-tuned synthesis of various cluster–based materials is presented. Providing custom-designed deposition stages and special sample holders it offers a high degree of control over the sample characteristics such as the cluster size, cluster amounts, and sample homogeneity in combination with high sample purity. The system is capable of producing thin films of pure clusters and various cluster-matrix combinations with cluster sizes ranging from single atoms up to aggregates of several thousand atoms. Two custom-designed deposition stages are available, one utilizes the full cluster beam, yielding micrograms of pure clusters within a few hours and the second one uses mass-separated clusters (mass-resolution between 2% and 10%), yielding nanograms of pure clusters in the same timescale. Furthermore, at the second deposition stage, a variety of matrix materials can be co-deposited at a controlled sample temperature between 153 K and 673 K. In order to prove the capabilities of the apparatus, a series of experiments with Fe clusters embedded in Ag matrices with different volume fractions of clusters were carried out. Energy dispersive X-ray spectroscopy measurements revealed that the amount of deposited clusters as well as the sample homogeneity can be controlled with an outstanding accuracy of 10%. Additional measurements of the magnetic properties indicated the presence of separated clusters for volume fractions of clusters around 2 volume percent (vol. %), while above this concentration (10 vol. %) a partial aggregation of the clusters was observed. It was also shown that the resulting thin films are nearly oxygen free, which ascertains that oxygen sensitive materials can be safely handled in this newly developed apparatus.

  13. Dynamically avoiding fine-tuning the cosmological constant: the ''Relaxed Universe''

    SciTech Connect

    Bauer, Florian; Solà, Joan; Štefancić, Hrvoje E-mail: sola@ecm.ub.es

    2010-12-01

    We demonstrate that there exists a large class of F(R,G) action functionals of the scalar curvature and of the Gauß-Bonnet invariant which are able to relax dynamically a large cosmological constant (CC), whatever it be its starting value in the early universe. Hence, it is possible to understand, without fine-tuning, the very small current value Λ{sub 0} ∼ H{sub 0}{sup 2} of the CC as compared to its theoretically expected large value in quantum field theory and string theory. In our framework, this relaxation appears as a pure gravitational effect, where no ad hoc scalar fields are needed. The action involves a positive power of a characteristic mass parameter, M, whose value can be, interestingly enough, of the order of a typical particle physics mass of the Standard Model of the strong and electroweak interactions or extensions thereof, including the neutrino mass. The model universe emerging from this scenario (the ''Relaxed Universe'') falls within the class of the so-called ΛXCDM models of the cosmic evolution. Therefore, there is a ''cosmon'' entity X (represented by an effective object, not a field), which in this case is generated by the effective functional F(R,G) and is responsible for the dynamical adjustment of the cosmological constant. This model universe successfully mimics the essential past epochs of the standard (or ''concordance'') cosmological model (ΛCDM). Furthermore, it provides interesting clues to the coincidence problem and it may even connect naturally with primordial inflation.

  14. Photoassisted photoluminescence fine-tuning of gold nanodots through free radical-mediated ligand-assembly.

    PubMed

    Tseng, Yu-Ting; Cherng, Rochelle; Harroun, Scott G; Yuan, Zhiqin; Lin, Tai-Yuan; Wu, Chien-Wei; Chang, Huan-Tsung; Huang, Chih-Ching

    2016-05-14

    In this study, we have developed a simple photoassisted ligand assembly to fine-tune the photoluminescence (PL) of (11-mercaptoundecyl)-N,N,N-trimethylammonium bromide-capped gold nanodots (11-MUTAB-Au NDs). The 11-MUTAB-Au NDs (size: ca. 1.8 nm), obtained from the reaction of gold nanoparticles (ca. 3 nm) and 11-MUTAB, exhibited weak, near-infrared (NIR) PL at 700 nm with a quantum yield (QY) of 0.37% upon excitation at 365 nm. The PL QY of the Au NDs increased to 11.43% after reaction with 11-mercaptoundecanoic acid (11-MUA) for 30 min under ultraviolet (UV) light, which was accompanied by a PL wavelength shift to the green region (∼520 nm). UV-light irradiation accelerates 11-MUA assembly on the 11-MUTABAu NDs (11-MUA/11-MUTAB-Au NDs) through a radical-mediated reaction. Furthermore, the PL wavelength of the 11-MUA/11-MUTAB-Au NDs can be switched to 640 nm via cysteamine under UV-light irradiation. We propose that the PL of the Au NDs with NIR and visible emissions was originally from the surface thiol-Au complexes and the Au core, respectively. These dramatically different optical properties of the Au NDs were due to variation in the surface ligands, as well as the densities and surface oxidant states of the surface Au atoms/ions. These effects can be controlled by assembling surface thiol ligands and accelerated by UV irradiation. PMID:27118444

  15. Body appendages fine-tune posture and moments in freely manoeuvring fruit flies.

    PubMed

    Berthé, Ruben; Lehmann, Fritz-Olaf

    2015-10-01

    The precise control of body posture by turning moments is key to elevated locomotor performance in flying animals. Although elevated moments for body stabilization are typically produced by wing aerodynamics, animals also steer using drag on body appendages, shifting their centre of body mass, and changing moments of inertia caused by active alterations in body shape. To estimate the instantaneous contribution of each of these components for posture control in an insect, we three-dimensionally reconstructed body posture and movements of body appendages in freely manoeuvring fruit flies (Drosophila melanogaster) by high-speed video and experimentally scored drag coefficients of legs and body trunk at low Reynolds number. The results show that the sum of leg- and abdomen-induced yaw moments dominates wing-induced moments during 17% of total flight time but is, on average, 7.2-times (roll, 3.4-times) smaller during manoeuvring. Our data reject a previous hypothesis on synergistic moment support, indicating that drag on body appendages and mass-shift inhibit rather than support turning moments produced by the wings. Numerical modelling further shows that hind leg extension alters the moments of inertia around the three main body axes of the animal by not more than 6% during manoeuvring, which is significantly less than previously reported for other insects. In sum, yaw, pitch and roll steering by body appendages probably fine-tune turning behaviour and body posture, without providing a significant advantage for posture stability and moment support. Motion control of appendages might thus be part of the insect's trimming reflexes, which reduce imbalances in moment generation caused by unilateral wing damage and abnormal asymmetries of the flight apparatus. PMID:26347566

  16. A role for TRIANGULAR HULL1 in fine-tuning spikelet morphogenesis in rice.

    PubMed

    Sato, Dai-Suke; Ohmori, Yoshihiro; Nagashima, Haruka; Toriba, Taiyo; Hirano, Hiro-Yuki

    2014-01-01

    The lemma and palea, which enclose the pistil, stamens, and lodicules, are the most conspicuous organs in the rice spikelet. We isolated a mutant line (ng6569) in which the lemma and palea were narrower than those of the wild type, and found that the mutant had a defect in TRIANGULAR HULL1 (TH1), which encodes a nuclear protein with an ALOG domain. Detailed morphological analysis indicated that the th1 mutation caused a reduction in the size of tubercles, which are convex structures on the surface of the lemma and palea. This reduction was more pronounced in the apical region of the lemma than in the basal region, resulting in the formation of a beak-like spikelet. By contrast, the number of tubercle rows and their spatial distribution on the lemma were not affected in the th1 mutant. Thus, the TH1 gene seems to be involved in fine-tuning the morphogenesis of the lemma and palea. In situ hybridization analysis revealed that TH1 was highly expressed in the primordia of the lemma and palea, but only weakly expressed in the primordia of the sterile lemma and rudimentary glume. We then examined the effect of th1 mutation on the lemma-like structure formed in the long sterile lemma/glume1 (g1) and extra glume1 (eg1) mutants. The result showed that the th1 mutation strongly affected the morphology of the extra lemma of eg1, but had no significant effect on the transformed lemma of g1. PMID:25224972

  17. High-temperature superconductivity from fine-tuning of Fermi-surface singularities in iron oxypnictides

    PubMed Central

    Charnukha, A.; Evtushinsky, D. V.; Matt, C. E.; Xu, N.; Shi, M.; Büchner, B.; Zhigadlo, N. D.; Batlogg, B.; Borisenko, S. V.

    2015-01-01

    In the family of the iron-based superconductors, the REFeAsO-type compounds (with RE being a rare-earth metal) exhibit the highest bulk superconducting transition temperatures (Tc) up to 55 K and thus hold the key to the elusive pairing mechanism. Recently, it has been demonstrated that the intrinsic electronic structure of SmFe0.92Co0.08AsO (Tc = 18 K) is highly nontrivial and consists of multiple band-edge singularities in close proximity to the Fermi level. However, it remains unclear whether these singularities are generic to the REFeAsO-type materials and if so, whether their exact topology is responsible for the aforementioned record Tc. In this work, we use angle-resolved photoemission spectroscopy (ARPES) to investigate the inherent electronic structure of the NdFeAsO0.6F0.4 compound with a twice higher Tc = 38 K. We find a similarly singular Fermi surface and further demonstrate that the dramatic enhancement of superconductivity in this compound correlates closely with the fine-tuning of one of the band-edge singularities to within a fraction of the superconducting energy gap Δ below the Fermi level. Our results provide compelling evidence that the band-structure singularities near the Fermi level in the iron-based superconductors must be explicitly accounted for in any attempt to understand the mechanism of superconducting pairing in these materials. PMID:26678565

  18. Cell-Specific Fine-Tuning of Neuronal Excitability by Differential Expression of Modulator Protein Isoforms

    PubMed Central

    Jepson, James; Sheldon, Amanda; Shahidullah, Mohammad; Fei, Hong; Koh, Kyunghee

    2013-01-01

    SLOB (SLOWPOKE-binding protein) modulates the Drosophila SLOWPOKE calcium-activated potassium channel. We have shown previously that SLOB deletion or RNAi knockdown decreases excitability of neurosecretory pars intercerebralis (PI) neurons in the adult Drosophila brain. In contrast, we found that SLOB deletion/knockdown enhances neurotransmitter release from motor neurons at the fly larval neuromuscular junction, suggesting an increase in excitability. Because two prominent SLOB isoforms, SLOB57 and SLOB71, modulate SLOWPOKE channels in opposite directions in vitro, we investigated whether divergent expression patterns of these two isoforms might underlie the differential modulation of excitability in PI and motor neurons. By performing detailed in vitro and in vivo analysis, we found strikingly different modes of regulatory control by the slob57 and slob71 promoters. The slob71, but not slob57, promoter contains binding sites for the Hunchback and Mirror transcriptional repressors. Furthermore, several core promoter elements that are absent in the slob57 promoter coordinately drive robust expression of a luciferase vector by the slob71 promoter in vitro. In addition, we visualized the expression patterns of the slob57 and slob71 promoters in vivo and found clear spatiotemporal differences in promoter activity. SLOB57 is expressed prominently in adult PI neurons, whereas larval motor neurons exclusively express SLOB71. In contrast, at the larval neuromuscular junction, SLOB57 expression appears to be restricted mainly to a subset of glial cells. Our results illustrate how the use of alternative transcriptional start sites within an ion channel modulator locus coupled with functionally relevant alternative splicing can be used to fine-tune neuronal excitability in a cell-specific manner. PMID:24133277

  19. Measured and calculated acoustic attenuation rates of tuned resonator arrays for two surface impedance distribution models with flow

    NASA Technical Reports Server (NTRS)

    Parrott, Tony L.; Abrahamson, A. Louis; Jones, Michael G.

    1988-01-01

    An experiment was performed to validate two analytical models for predicting low frequency attenuation of duct liner configurations built from an array of seven resonators that could be individually tuned via adjustable cavity depths. These analytical models had previously been developed for high frequency aero-engine inlet duct liner design. In the low frequency application, the liner surface impedance distribution is unavoidably spatially varying by virtue of available fabrication techniques. The characteristic length of this spatial variation may be a significant fraction of the acoustic wavelength. Comparison of measured and predicted attenuation rates and transmission losses for both modal decomposition and finite element propagation models were in good to excellent agreement for a test frequency range that included the first and second cavity resonance frequencies. This was true for either of two surface impedance distribution modeling procedures used to simplify the impedance boundary conditions. In the presence of mean flow, measurements revealed a fine scale structure of acoustic hot spots in the attenuation and phase profiles. These details were accurately predicted by the finite element model. Since no impedance changes due to mean flow were assumed, it is concluded that this fine scale structure was due to convective effects of the mean flow interacting with the surface impedance nonuniformities.

  20. Fine-tuning of single-molecule conductance by tweaking both electronic structure and conformation of side substituents.

    PubMed

    Aragonès, Albert C; Darwish, Nadim; Im, JongOne; Lim, Boram; Choi, Jeongae; Koo, Sangho; Díez-Pérez, Ismael

    2015-05-18

    Herein, we describe a method to fine-tune the conductivity of single-molecule wires by employing a combination of chemical composition and geometrical modifications of multiple phenyl side groups as conductance modulators embedded along the main axis of the electronic pathway. We have measured the single-molecule conductivity of a novel series of phenyl-substituted carotenoid wires whose conductivity can be tuned with high precision over an order of magnitude range by modulating both the electron-donating character of the phenyl substituent and its dihedral angle. It is demonstrated that the electronic communication between the phenyl side groups and the molecular wire is maximized when the phenyl groups are twisted closer to the plane of the conjugated molecular wire. These findings can be refined to a general technique for precisely tuning the conductivity of molecular wires. PMID:25847688

  1. A composite Higgs model with minimal fine-tuning: The large-N and weak-technicolor limit

    NASA Astrophysics Data System (ADS)

    Lane, Kenneth

    2014-11-01

    We suggest a criterion to minimize the amount of fine-tuning in a composite Higgs model. The paradigm of this type of model is the top-condensate model of Bardeen-Hill-Lindner. Although "minimally fine-tuned," this model fails to account correctly for the masses of the top quark and the 125 GeV Higgs boson. We propose a generalization of the Bardeen-Hill-Lindner model that employs finely tuned extended technicolor plus technicolor (TC) interactions. The additional freedom of this model may accommodate both mt(173 ) and MH(125 ). This paper studies the large-NTC and -NC limit of this model in which technicolor is weak and does not contribute to electroweak symmetry breaking. Refinements including walking-TC dynamics and a renormalization-group analysis of mt and MH will appear in a subsequent paper. A likely generic signal of this model is enhanced production of longitudinally polarized weak bosons, alone and in association with H (125 ).

  2. Tuning of Kilopixel Transition Edge Sensor Bolometer Arrays with a Digital Frequency Multiplexed Readout System

    NASA Astrophysics Data System (ADS)

    MacDermid, Kevin; Hyland, Peter; Aubin, Francois; Bissonnette, Eric; Dobbs, Matt; Hubmayr, Johannes; Smecher, Graeme; Wairrach, Shahjahen

    2009-12-01

    A digital frequency multiplexing (DfMUX) system has been developed and used to tune large arrays of transition edge sensor (TES) bolometers read out with SQUID arrays for mm-wavelength cosmology telescopes. The DfMUX system multiplexes the input bias voltages and output currents for several bolometers on a single set of cryogenic wires. Multiplexing reduces the heat load on the camera's sub-Kelvin cryogenic detector stage. In this paper we describe the algorithms and software used to set up and optimize the operation of the bolometric camera. The algorithms are implemented on soft processors embedded within FPGA devices operating on each backend readout board. The result is a fully parallelized implementation for which the setup time is independent of the array size.

  3. Dry Oxidation and Vacuum Annealing Treatments for Tuning the Wetting Properties of Carbon Nanotube Arrays

    PubMed Central

    Aria, Adrianus Indrat; Gharib, Morteza

    2013-01-01

    In this article, we describe a simple method to reversibly tune the wetting properties of vertically aligned carbon nanotube (CNT) arrays. Here, CNT arrays are defined as densely packed multi-walled carbon nanotubes oriented perpendicular to the growth substrate as a result of a growth process by the standard thermal chemical vapor deposition (CVD) technique.1,2 These CNT arrays are then exposed to vacuum annealing treatment to make them more hydrophobic or to dry oxidation treatment to render them more hydrophilic. The hydrophobic CNT arrays can be turned hydrophilic by exposing them to dry oxidation treatment, while the hydrophilic CNT arrays can be turned hydrophobic by exposing them to vacuum annealing treatment. Using a combination of both treatments, CNT arrays can be repeatedly switched between hydrophilic and hydrophobic.2 Therefore, such combination show a very high potential in many industrial and consumer applications, including drug delivery system and high power density supercapacitors.3-5 The key to vary the wettability of CNT arrays is to control the surface concentration of oxygen adsorbates. Basically oxygen adsorbates can be introduced by exposing the CNT arrays to any oxidation treatment. Here we use dry oxidation treatments, such as oxygen plasma and UV/ozone, to functionalize the surface of CNT with oxygenated functional groups. These oxygenated functional groups allow hydrogen bond between the surface of CNT and water molecules to form, rendering the CNT hydrophilic. To turn them hydrophobic, adsorbed oxygen must be removed from the surface of CNT. Here we employ vacuum annealing treatment to induce oxygen desorption process. CNT arrays with extremely low surface concentration of oxygen adsorbates exhibit a superhydrophobic behavior. PMID:23629482

  4. Decoding techniques for fine-fine geometry multi-anode microchannel arrays

    NASA Technical Reports Server (NTRS)

    Kasle, David B.

    1988-01-01

    The Multi-Anode Microchannel Array (MAMA) is a photon-counting detector which decodes the position of an event through coincidence discrimination. The decoding algorithm which associates a given event with the appropriate pixel is determined by the geometry of the array. The decoding process can be divided into two tasks: anode encoding and pixel decoding. Techniques for performing both tasks are described and contrasted in light of application requirements. Decode times of 75 nanoseconds have been achieved, and considerably faster decoders are possible given new architectures and technologies.

  5. Nanostructured Arrays Formed by Finely Focused Ion Beams

    SciTech Connect

    Budai, J.D.; Datsos, P.G.; Feldman, L.C.; Heinig, K.-H.; Meldrum, A.; Strobel, M.; Thomas, K.A.; Warmack, R.J.; White, C.W.; Zuhr, R.A.

    1998-11-30

    Amorphous, polycrystalline, and single crystal nanometer dimension particles can be formed in a variety of substrates by ion implantation and subsequent annealing. Such composite colloidal materials exhibit unique optical properties that could be useful in optical devices, switches, and waveguides. However colloids formed by blanket implantation are not uniform in size due to the nonuniform density of the implant, resulting in diminution of the size dependent optical properties. The object of the present work is to form more uniform size particles arranged in a 2-dimensional lattice by using a finely focused ion beam to implant identical ion doses only into nanometer size regions located at each point of a rectangular lattice. Initial work is being done with a 30 keV Ga beam implanted into Si. Results of particle formation as a function of implant conditions as analyzed by Rutherford backscattering, x-ray analysis, atomic force microscopy, and both scanning and transmission electron microscopy will be presented and discussed.

  6. Survey of plasmonic gaps tuned at sub-nanometer scale in self-assembled arrays

    NASA Astrophysics Data System (ADS)

    Qian, Li-Hua; Yi, Li-Zhi; Wang, Gui-Sheng; Zhang, Chao; Yuan, Song-Liu

    2016-04-01

    Creating nanoscale and sub-nanometer gaps between noble metal nanoparticles is critical for the applications of plasmonics and nanophotonics. To realize simultaneous attainments of both the optical spectrum and the gap size, the ability to tune these nanoscale gaps at the sub-nanometer scale is particularly desirable. Many nanofabrication methodologies, including electron beam lithography, self-assembly, and focused ion beams, have been tested for creating nanoscale gaps that can deliver significant field enhancement. Here, we survey recent progress in both the reliable creation of nanoscale gaps in nanoparticle arrays using self-assemblies and in the in-situ tuning techniques at the sub-nanometer scale. Precisely tunable gaps, as we expect, will be good candidates for future investigations of surface-enhanced Raman scattering, non-linear optics, and quantum plasmonics.

  7. Coupling and tuning of modal frequencies in direct current biased microelectromechanical systems arrays

    NASA Astrophysics Data System (ADS)

    Kambali, Prashant N.; Swain, Gyanadutta; Pandey, Ashok Kumar; Buks, Eyal; Gottlieb, Oded

    2015-08-01

    Understanding the coupling of different modal frequencies and their tuning mechanisms has become essential to design multi-frequency MEMS devices. In this work, we fabricate a MEMS beam with fixed boundaries separated from two side electrodes and a bottom electrode. Subsequently, we perform experiments to obtain the frequency variation of in-plane and out-of-plane mechanical modes of the microbeam with respect to both DC bias and laser heating. We show that the frequencies of the two modes coincide at a certain DC bias, which in turn can also be varied due to temperature. Subsequently, we develop a theoretical model to predict the variation of the two modes and their coupling due to a variable gap between the microbeam and electrodes, initial tension, and fringing field coefficients. Finally, we discuss the influence of frequency tuning parameters in arrays of 3, 33, and 40 microbeams, respectively. It is also found that the frequency bandwidth of a microbeam array can be increased to as high as 25 kHz for a 40 microbeam array with a DC bias of 80 V.

  8. Coupling and tuning of modal frequencies in direct current biased microelectromechanical systems arrays

    SciTech Connect

    Kambali, Prashant N.; Swain, Gyanadutta; Pandey, Ashok Kumar; Buks, Eyal; Gottlieb, Oded

    2015-08-10

    Understanding the coupling of different modal frequencies and their tuning mechanisms has become essential to design multi-frequency MEMS devices. In this work, we fabricate a MEMS beam with fixed boundaries separated from two side electrodes and a bottom electrode. Subsequently, we perform experiments to obtain the frequency variation of in-plane and out-of-plane mechanical modes of the microbeam with respect to both DC bias and laser heating. We show that the frequencies of the two modes coincide at a certain DC bias, which in turn can also be varied due to temperature. Subsequently, we develop a theoretical model to predict the variation of the two modes and their coupling due to a variable gap between the microbeam and electrodes, initial tension, and fringing field coefficients. Finally, we discuss the influence of frequency tuning parameters in arrays of 3, 33, and 40 microbeams, respectively. It is also found that the frequency bandwidth of a microbeam array can be increased to as high as 25 kHz for a 40 microbeam array with a DC bias of 80 V.

  9. Tuning exciton energy and fine-structure splitting in single InAs quantum dots by applying uniaxial stress

    NASA Astrophysics Data System (ADS)

    Su, Dan; Dou, Xiuming; Wu, Xuefei; Liao, Yongping; Zhou, Pengyu; Ding, Kun; Ni, Haiqiao; Niu, Zhichuan; Zhu, Haijun; Jiang, Desheng; Sun, Baoquan

    2016-04-01

    Exciton and biexciton emission energies as well as excitonic fine-structure splitting (FSS) in single InAs/GaAs quantum dots (QDs) have been continuously tuned in situ in an optical cryostat using a developed uniaxial stress device. With increasing tensile stress, the red shift of excitonic emission is up to 5 nm; FSS decreases firstly and then increases monotonically, reaching a minimum value of approximately 10 μeV; biexciton binding energy decreases from 460 to 106 μeV. This technique provides a simple and convenient means to tune QD structural symmetry, exciton energy and biexciton binding energy and can be used for generating entangled and indistinguishable photons.

  10. Polarization-tuned Dynamic Color Filters Incorporating a Dielectric-loaded Aluminum Nanowire Array

    PubMed Central

    Raj Shrestha, Vivek; Lee, Sang-Shin; Kim, Eun-Soo; Choi, Duk-Yong

    2015-01-01

    Nanostructured spectral filters enabling dynamic color-tuning are saliently attractive for implementing ultra-compact color displays and imaging devices. Realization of polarization-induced dynamic color-tuning via one-dimensional periodic nanostructures is highly challenging due to the absence of plasmonic resonances for transverse-electric polarization. Here we demonstrate highly efficient dynamic subtractive color filters incorporating a dielectric-loaded aluminum nanowire array, providing a continuum of customized color according to the incident polarization. Dynamic color filtering was realized relying on selective suppression in transmission spectra via plasmonic resonance at a metal-dielectric interface and guided-mode resonance for a metal-clad dielectric waveguide, each occurring at their characteristic wavelengths for transverse-magnetic and electric polarizations, respectively. A broad palette of colors, including cyan, magenta, and yellow, has been attained with high transmission beyond 80%, by tailoring the period of the nanowire array and the incident polarization. Thanks to low cost, high durability, and mass producibility of the aluminum adopted for the proposed devices, they are anticipated to be diversely applied to color displays, holographic imaging, information encoding, and anti-counterfeiting. PMID:26211625

  11. Polarization-tuned Dynamic Color Filters Incorporating a Dielectric-loaded Aluminum Nanowire Array

    NASA Astrophysics Data System (ADS)

    Raj Shrestha, Vivek; Lee, Sang-Shin; Kim, Eun-Soo; Choi, Duk-Yong

    2015-07-01

    Nanostructured spectral filters enabling dynamic color-tuning are saliently attractive for implementing ultra-compact color displays and imaging devices. Realization of polarization-induced dynamic color-tuning via one-dimensional periodic nanostructures is highly challenging due to the absence of plasmonic resonances for transverse-electric polarization. Here we demonstrate highly efficient dynamic subtractive color filters incorporating a dielectric-loaded aluminum nanowire array, providing a continuum of customized color according to the incident polarization. Dynamic color filtering was realized relying on selective suppression in transmission spectra via plasmonic resonance at a metal-dielectric interface and guided-mode resonance for a metal-clad dielectric waveguide, each occurring at their characteristic wavelengths for transverse-magnetic and electric polarizations, respectively. A broad palette of colors, including cyan, magenta, and yellow, has been attained with high transmission beyond 80%, by tailoring the period of the nanowire array and the incident polarization. Thanks to low cost, high durability, and mass producibility of the aluminum adopted for the proposed devices, they are anticipated to be diversely applied to color displays, holographic imaging, information encoding, and anti-counterfeiting.

  12. Focal plane array based infrared thermography in fine physical experiment

    NASA Astrophysics Data System (ADS)

    Vainer, Boris G.

    2008-03-01

    By two examples of dissimilar physical phenomena causing thermophysical effects, the unique capabilities of one of the up-to-date methods of experimental physics—focal plane array (FPA) based infrared (IR) thermography (IRT), are demonstrated distinctly. Experimenters inexperienced in IRT can grasp how this method provides a means for combining real-time visualization with quantitative analysis. A narrow-band short-wavelength IR camera was used in the experiments. It is discussed and stated that IRT is best matched and suited to the next two test conditions—when a heated specimen is thin and when heat is generated in the immediate region of a surface of a solid. The first prerequisite is realized in the search for directional patterns of combined low-power radiation sources with the use of the IRT-aided method. The second one is realized in studies of water vapour adsorption on uneven (irregular) surfaces of solid materials. With multiple swatches taken from a set of different fabrics and used as experimental samples, a sharp distinction between adsorptivities of their surfaces is strikingly illustrated by IRT time-domain measurements exhibiting the associated thermal effect ranging within an order of magnitude. It is justified that the described IRT-aided test can find practical implementation at least in the light industry. Emissivities of different fabrics are evaluated experimentally with the described reflection method based on the narrow spectral range of IRT. On the basis of direct IR observations, attention is paid to the need for close control over the surface temperature increase while the adsorption isotherms are being measured. Sensitivity of the FPA-based IRT method, as applied to examine the kinetics of initial stages of adsorption of gaseous molecules on the solid surface, is evaluated analytically and quantitatively. The relationship between the amount of adsorbate and the measurable excess of adsorbent temperature is found. It is discovered

  13. Fine Tuning of Chlorophyll Spectra by Protein-Induced Ring Deformation.

    PubMed

    Bednarczyk, Dominika; Dym, Orly; Prabahar, Vadivel; Peleg, Yoav; Pike, Douglas H; Noy, Dror

    2016-06-01

    The ability to tune the light-absorption properties of chlorophylls by their protein environment is the key to the robustness and high efficiency of photosynthetic light-harvesting proteins. Unfortunately, the intricacy of the natural complexes makes it very difficult to identify and isolate specific protein-pigment interactions that underlie the spectral-tuning mechanisms. Herein we identify and demonstrate the tuning mechanism of chlorophyll spectra in type II water-soluble chlorophyll binding proteins from Brassicaceae (WSCPs). By comparing the molecular structures of two natural WSCPs we correlate a shift in the chlorophyll red absorption band with deformation of its tetrapyrrole macrocycle that is induced by changing the position of a nearby tryptophan residue. We show by a set of reciprocal point mutations that this change accounts for up to 2/3 of the observed spectral shift between the two natural variants. PMID:27098554

  14. Broadband, continuous, and fine-tune properties of external-cavity thermoelectric-stabilized mid-infrared quantum-cascade lasers.

    PubMed

    Peng, Chuan; Luo, Guipeng; Le, Han Q

    2003-08-20

    Continuous, broad, and single-mode wavelength tuning of thermoelectrically cooled short-pulse quantum-cascade lasers is demonstrated with a combination of coarse grating tuning and fine phase tuning of the gain element. This approach overcomes the problem of a poor facet antireflection coating of the gain chip by shifting a Fabry-Perot longitudinal mode to coincide with the desired grating-selected wavelength. The 9-microm laser was tested with NH3 gas absorption and showed fine frequency tuning at a rate of 31 MHz/step and a time-averaged linewidth of 500-750 MHz. The total tuning range was 9.08-9.36 microm and was limited only by the intrinsic gain of the device. PMID:12952334

  15. The WD40 Domain Protein MSI1 Functions in a Histone Deacetylase Complex to Fine-Tune Abscisic Acid Signaling.

    PubMed

    Mehdi, Saher; Derkacheva, Maria; Ramström, Margareta; Kralemann, Lejon; Bergquist, Jonas; Hennig, Lars

    2016-01-01

    MSI1 belongs to a family of histone binding WD40-repeat proteins. Arabidopsis thaliana contains five genes encoding MSI1-like proteins, but their functions in diverse chromatin-associated complexes are poorly understood. Here, we show that MSI1 is part of a histone deacetylase complex. We copurified HISTONE DEACETYLASE19 (HDA19) with MSI1 and transcriptional regulatory SIN3-like proteins and provide evidence that MSI1 and HDA19 associate into the same complex in vivo. These data suggest that MSI1, HDA19, and HISTONE DEACETYLATION COMPLEX1 protein form a core complex that can integrate various SIN3-like proteins. We found that reduction of MSI1 or HDA19 causes upregulation of abscisic acid (ABA) receptor genes and hypersensitivity of ABA-responsive genes. The MSI1-HDA19 complex fine-tunes ABA signaling by binding to the chromatin of ABA receptor genes and by maintaining low levels of acetylation of histone H3 at lysine 9, thereby affecting the expression levels of ABA receptor genes. Reduced MSI1 or HDA19 levels led to increased tolerance to salt stress corresponding to the increased ABA sensitivity of gene expression. Together, our results reveal the presence of an MSI1-HDA19 complex that fine-tunes ABA signaling in Arabidopsis. PMID:26704384

  16. Expression analysis of aquaporins from desert truffle mycorrhizal symbiosis reveals a fine-tuned regulation under drought.

    PubMed

    Navarro-Ródenas, Alfonso; Bárzana, Gloria; Nicolás, Emilio; Carra, Andrea; Schubert, Andrea; Morte, Asunción

    2013-09-01

    We have performed the isolation, functional characterization, and expression analysis of aquaporins in roots and leaves of Helianthemum almeriense, in order to evaluate their roles in tolerance to water deficit. Five cDNAs, named HaPIP1;1, HaPIP1;2, HaPIP2;1, HaPIP2;2, and HaTIP1;1, were isolated from H. almeriense. A phylogenetic analysis of deduced proteins confirmed that they belong to the water channel proteins family. The HaPIP1;1, HaPIP2;1, and HaTIP1;1 genes encode functional water channel proteins, as indicated by expression assays in Saccharomyces cerevisiae, showing divergent roles in the transport of water, CO2, and NH3. The expression patterns of the genes isolated from H. almeriense and of a previously described gene from Terfezia claveryi (TcAQP1) were analyzed in mycorrhizal and nonmycorrhizal plants cultivated under well-watered or drought-stress conditions. Some of the studied aquaporins were subjected to fine-tuned expression only under drought-stress conditions. A beneficial effect on plant physiological parameters was observed in mycorrhizal plants with respect to nonmycorrhizal ones. Moreover, stress induced a change in the mycorrhizal type formed, which was more intracellular under drought stress. The combination of a high intracellular colonization, together with the fine-tuned expression of aquaporins could result in a morphophysiological adaptation of this symbiosis to drought conditions. PMID:23656332

  17. Using membrane composition to fine-tune the pKa of an optical liposome pH sensor†

    PubMed Central

    Clear, Kasey J.; Virga, Katelyn; Gray, Lawrence

    2016-01-01

    Liposomes containing membrane-anchored pH-sensitive optical probes are valuable sensors for monitoring pH in various biomedical samples. The dynamic range of the sensor is maximized when the probe pKa is close to the expected sample pH. While some biomedical samples are close to neutral pH there are several circumstances where the pH is 1 or 2 units lower. Thus, there is a need to fine-tune the probe pKa in a predictable way. This investigation examined two lipid-conjugated optical probes, each with appended deep-red cyanine dyes containing indoline nitrogen atoms that are protonated in acid. The presence of anionic phospholipids in the liposomes stabilized the protonated probes and increased the probe pKa values by < 1 unit. The results show that rational modification of the membrane composition is a general non-covalent way to fine-tune the pKa of an optical liposome sensor for optimal pH sensing performance. PMID:27087967

  18. The lesson of causal discovery algorithms for quantum correlations: causal explanations of Bell-inequality violations require fine-tuning

    NASA Astrophysics Data System (ADS)

    Wood, Christopher J.; Spekkens, Robert W.

    2015-03-01

    An active area of research in the fields of machine learning and statistics is the development of causal discovery algorithms, the purpose of which is to infer the causal relations that hold among a set of variables from the correlations that these exhibit . We apply some of these algorithms to the correlations that arise for entangled quantum systems. We show that they cannot distinguish correlations that satisfy Bell inequalities from correlations that violate Bell inequalities, and consequently that they cannot do justice to the challenges of explaining certain quantum correlations causally. Nonetheless, by adapting the conceptual tools of causal inference, we can show that any attempt to provide a causal explanation of nonsignalling correlations that violate a Bell inequality must contradict a core principle of these algorithms, namely, that an observed statistical independence between variables should not be explained by fine-tuning of the causal parameters. In particular, we demonstrate the need for such fine-tuning for most of the causal mechanisms that have been proposed to underlie Bell correlations, including superluminal causal influences, superdeterminism (that is, a denial of freedom of choice of settings), and retrocausal influences which do not introduce causal cycles.

  19. Fine tune W-CMP process with alignment mark selection for optimal metal layer overlay and yield benefits

    NASA Astrophysics Data System (ADS)

    Cui, Yuanting; So, Albert; Louks, Sean

    2004-05-01

    Alignment performance and overlay control of metal layer from W-CMP process highly depends on the process influence on the alignment mark. While in a manufacturing environment, there could be introduced many changes into W-CMP process for defect reduction, cost reduction and yield improvement to further guarantee our success in this highly competitive industry. This study characterizes the CMP effect, especially erosion and dishing effect, polishing selectivity on alignment mark profile, which results in different alignment performance. We illustrate that how we seek solution to achieve an optimal alignment performance with the existing mark in according to different CMP slurry process by further fine tuning W-CMP process, such as over-polishing, final polish. The CMP effect on different alignment mark types is also evaluated; future alignment mark selection and design based on future CMP process, film deposition can thus be proposed. This work explains a good working method of optimizing alignment for process, fine tuning process for alignment mark, feed-backing solutions for mark selection while taking into considerations of cost, throughput, defect, yield.

  20. Multiple excitatory and inhibitory neural signals converge to fine-tune Caenorhabditis elegans feeding to food availability.

    PubMed

    Dallière, Nicolas; Bhatla, Nikhil; Luedtke, Zara; Ma, Dengke K; Woolman, Jonathan; Walker, Robert J; Holden-Dye, Lindy; O'Connor, Vincent

    2016-02-01

    How an animal matches feeding to food availability is a key question for energy homeostasis. We addressed this in the nematode Caenorhabditis elegans, which couples feeding to the presence of its food (bacteria) by regulating pharyngeal activity (pumping). We scored pumping in the presence of food and over an extended time course of food deprivation in wild-type and mutant worms to determine the neural substrates of adaptive behavior. Removal of food initially suppressed pumping but after 2 h this was accompanied by intermittent periods of high activity. We show pumping is fine-tuned by context-specific neural mechanisms and highlight a key role for inhibitory glutamatergic and excitatory cholinergic/peptidergic drives in the absence of food. Additionally, the synaptic protein UNC-31 [calcium-activated protein for secretion (CAPS)] acts through an inhibitory pathway not explained by previously identified contributions of UNC-31/CAPS to neuropeptide or glutamate transmission. Pumping was unaffected by laser ablation of connectivity between the pharyngeal and central nervous system indicating signals are either humoral or intrinsic to the enteric system. This framework in which control is mediated through finely tuned excitatory and inhibitory drives resonates with mammalian hypothalamic control of feeding and suggests that fundamental regulation of this basic animal behavior may be conserved through evolution from nematode to human. PMID:26514165

  1. High-resolution dynamic pressure sensor array based on piezo-phototronic effect tuned photoluminescence imaging.

    PubMed

    Peng, Mingzeng; Li, Zhou; Liu, Caihong; Zheng, Qiang; Shi, Xieqing; Song, Ming; Zhang, Yang; Du, Shiyu; Zhai, Junyi; Wang, Zhong Lin

    2015-03-24

    A high-resolution dynamic tactile/pressure display is indispensable to the comprehensive perception of force/mechanical stimulations such as electronic skin, biomechanical imaging/analysis, or personalized signatures. Here, we present a dynamic pressure sensor array based on pressure/strain tuned photoluminescence imaging without the need for electricity. Each sensor is a nanopillar that consists of InGaN/GaN multiple quantum wells. Its photoluminescence intensity can be modulated dramatically and linearly by small strain (0-0.15%) owing to the piezo-phototronic effect. The sensor array has a high pixel density of 6350 dpi and exceptional small standard deviation of photoluminescence. High-quality tactile/pressure sensing distribution can be real-time recorded by parallel photoluminescence imaging without any cross-talk. The sensor array can be inexpensively fabricated over large areas by semiconductor product lines. The proposed dynamic all-optical pressure imaging with excellent resolution, high sensitivity, good uniformity, and ultrafast response time offers a suitable way for smart sensing, micro/nano-opto-electromechanical systems. PMID:25712580

  2. Postfunctionalization of BN-embedded polycyclic aromatic compounds for fine-tuning of their molecular properties.

    PubMed

    Wang, Xiao-Ye; Yang, Dong-Chu; Zhuang, Fang-Dong; Liu, Jia-Jie; Wang, Jie-Yu; Pei, Jian

    2015-06-01

    New BN-embedded, thiophene-fused, polycyclic aromatic compounds with planar geometry were designed and synthesized. The molecules showed excellent stability and chemical robustness. Postfunctionalization on this skeleton was demonstrated with a series of electrophilic bromination, palladium-catalyzed cross-coupling, and Knoevenagel condensation reactions. The π skeleton remained intact during these late-stage transformations. The optical and electronic properties have been well tuned through incorporation of electron-rich and -deficient groups on the backbone. This work shows the great advantage of the postfunctionalization strategy on BN-containing polycyclic aromatic compounds for fast diversification and materials screening. PMID:25955825

  3. Perspective: Extremely fine tuning of doping enabled by combinatorial molecular-beam epitaxy

    SciTech Connect

    Wu, J.; Božović, I.

    2015-06-01

    Chemical doping provides an effective method to control the electric properties of complex oxides. However, the state-of-art accuracy in controlling doping is limited to about 1%. This hampers elucidation of the precise doping dependences of physical properties and phenomena of interest, such as quantum phase transitions. Using the combinatorial molecular beam epitaxy, we improve the accuracy in tuning the doping level by two orders of magnitude. We illustrate this novel method by two examples: a systematic investigation of the doping dependence of interface superconductivity, and a study of the competing ground states in the vicinity of the insulator-to-superconductor transition.

  4. Analysis of slotted-waveguide antenna array excited by tuning screws

    NASA Astrophysics Data System (ADS)

    Azar, Tony Joseph

    1998-10-01

    A radiating array consisting of Longitudinal, centered slots, excited by objects inside the waveguide have several advantages that makes it attractive for the broadcast industry. This dissertation analyses a waveguide with a slot in the center of its broad wall, excited by a tuning screw. The waveguide can be made to radiate at different channels and with different elevation patterns. Parameters of the analysis are post position and penetration and slot position and length. We present a Method of Moments analysis of such a unit element, consisting of screw and slot, and of two unit elements, including their mutual coupling. Also, a fast and accurate analysis of a truncated post is presented. The results are presented in the form of scattering matrices and the data are compared to the widely used finite element code HFSS. The post/slot combination is shown to be equivalent to a shunt element on a transmission line. In comparison with all available commercial software, it is found that our Method of Moments code is fast, accurate and efficient. It requires only normally available hardware and runs in a matter of minutes. The complete radiation pattern of an eight element array is shown.

  5. Fine-tuning of process conditions to improve product uniformity of polystyrene particles used for wind tunnel velocimetry

    NASA Technical Reports Server (NTRS)

    Ray, Asit K.

    1990-01-01

    Monodisperse polymer particles (having uniform diameter) were used for the last two decades in physical, biological, and chemical sciences. In NASA Langley Research Center monodisperse polystyrene particles are used in wind tunnel laser velocimeters. These polystyrene (PS) particles in latex form were formulated at the Engineering Laboratory of FENGD using emulsion-free emulsion polymerization. Monodisperse PS latices particles having different particle diameters were formulated and useful experimental data involving effects of process conditions on particle size were accumulated. However, similar process conditions and chemical recipes for polymerization of styrene monomer have often yielded monodisperse particles having varying diameters. The purpose was to improve the PS latex product uniformity by fine-tuning the process parameters based on the knowledge of suspension and emulsion polymerization.

  6. Functional Role of PPARs in Ruminants: Potential Targets for Fine-Tuning Metabolism during Growth and Lactation

    PubMed Central

    Chen, Shuowen; Khan, Muhammad J.; Loor, Juan J.

    2013-01-01

    Characterization and biological roles of the peroxisome proliferator-activated receptor (PPAR) isotypes are well known in monogastrics, but not in ruminants. However, a wealth of information has accumulated in little more than a decade on ruminant PPARs including isotype tissue distribution, response to synthetic and natural agonists, gene targets, and factors affecting their expression. Functional characterization demonstrated that, as in monogastrics, the PPAR isotypes control expression of genes involved in lipid metabolism, anti-inflammatory response, development, and growth. Contrary to mouse, however, the PPARγ gene network appears to controls milk fat synthesis in lactating ruminants. As in monogastrics, PPAR isotypes in ruminants are activated by long-chain fatty acids, therefore, making them ideal candidates for fine-tuning metabolism in this species via nutrients. In this regard, using information accumulated in ruminants and monogastrics, we propose a model of PPAR isotype-driven biological functions encompassing key tissues during the peripartal period in dairy cattle. PMID:23737762

  7. MicroRNA inhibition fine-tunes and provides robustness to the restriction point switch of the cell cycle

    PubMed Central

    del Rosario, Ricardo C. H.; Damasco, Joseph Ray Clarence G.; Aguda, Baltazar D.

    2016-01-01

    The restriction point marks a switch in G1 from growth factor-dependent to growth factor-independent progression of the cell cycle. The proper regulation of this switch is important for normal cell processes; aberrations could result in a number of diseases such as cancer, neurodegenerative disorders, stroke and myocardial infarction. To further understand the regulation of the restriction point, we extended a mathematical model of the Rb-E2F pathway to include members of the microRNA cluster miR-17-92. Our mathematical analysis shows that microRNAs play an essential role in fine-tuning and providing robustness to the switch. We also demonstrate how microRNA regulation can steer cells in or out of cancer states. PMID:27610602

  8. 3'-UTR engineering to improve soluble expression and fine-tuning of activity of cascade enzymes in Escherichia coli.

    PubMed

    Song, Ji-Won; Woo, Ji-Min; Jung, Gyoo Yeol; Bornscheuer, Uwe T; Park, Jin-Byung

    2016-01-01

    3'-Untranslated region (3'UTR) engineering was investigated to improve solubility of heterologous proteins (e.g., Baeyer-Villiger monooxygenases (BVMOs)) in Escherichia coli. Insertion of gene fragments containing putative RNase E recognition sites into the 3'UTR of the BVMO genes led to the reduction of mRNA levels in E. coli. Importantly, the amounts of soluble BVMOs were remarkably enhanced resulting in a proportional increase of in vivo catalytic activities. Notably, this increase in biocatalytic activity correlated to the number of putative RNase E endonucleolytic cleavage sites in the 3'UTR. For instance, the biotransformation activity of the BVMO BmoF1 (from Pseudomonas fluorescens DSM50106) in E. coli was linear to the number of RNase E cleavage sites in the 3'UTR. In summary, 3'UTR engineering can be used to improve the soluble expression of heterologous enzymes, thereby fine-tuning the enzyme activity in microbial cells. PMID:27406241

  9. Fine-tuning of a radical-based reaction by radical S-adenosyl-L-methionine tryptophan lyase.

    PubMed

    Sicoli, Giuseppe; Mouesca, Jean-Marie; Zeppieri, Laura; Amara, Patricia; Martin, Lydie; Barra, Anne-Laure; Fontecilla-Camps, Juan C; Gambarelli, Serge; Nicolet, Yvain

    2016-03-18

    The radical S-adenosyl-L-methionine tryptophan lyase NosL converts L-tryptophan into 3-methylindolic acid, which is a precursor in the synthesis of the thiopeptide antibiotic nosiheptide. Using electron paramagnetic resonance spectroscopy and multiple L-tryptophan isotopologues, we trapped and characterized radical intermediates that indicate a carboxyl fragment migration mechanism for NosL. This is in contrast to a proposed fragmentation-recombination mechanism that implied Cα-Cβ bond cleavage of L-tryptophan. Although NosL resembles related tyrosine lyases, subtle substrate motions in its active site are responsible for a fine-tuned radical chemistry, which selects the Cα-C bond for disruption. This mechanism highlights evolutionary adaptation to structural constraints in proteins as a route to alternative enzyme function. PMID:26989252

  10. MicroRNA inhibition fine-tunes and provides robustness to the restriction point switch of the cell cycle.

    PubMed

    Del Rosario, Ricardo C H; Damasco, Joseph Ray Clarence G; Aguda, Baltazar D

    2016-01-01

    The restriction point marks a switch in G1 from growth factor-dependent to growth factor-independent progression of the cell cycle. The proper regulation of this switch is important for normal cell processes; aberrations could result in a number of diseases such as cancer, neurodegenerative disorders, stroke and myocardial infarction. To further understand the regulation of the restriction point, we extended a mathematical model of the Rb-E2F pathway to include members of the microRNA cluster miR-17-92. Our mathematical analysis shows that microRNAs play an essential role in fine-tuning and providing robustness to the switch. We also demonstrate how microRNA regulation can steer cells in or out of cancer states. PMID:27610602

  11. Single Heteroatom Fine-Tuning of the Emissive Properties in Organoboron Complexes with 7-(Azaheteroaryl)indole Systems.

    PubMed

    Más-Montoya, Miriam; Usea, Laura; Espinosa Ferao, Arturo; Montenegro, María F; Ramírez de Arellano, Carmen; Tárraga, Alberto; Rodríguez-López, José N; Curiel, David

    2016-04-15

    The application of organoboron compounds as light-absorbing or light-emitting species in areas as relevant as organic electronics or biomedicine has motivated the search for new materials which contribute to the progress of those applications. This article reports the synthesis of four-coordinate boron complexes based on the unexplored 7-(azaheteroaryl)indole ligands. An easy synthetic approach has enabled the fine-tuning of the electronic structure of the organoboron species by modifying a heteroaromatic component in the conjugated system. Furthermore, a comprehensive characterization by X-ray diffraction, absorption and emission spectroscopy, both in solution and in the solid state, cyclic voltammetry, and computational methods has evidenced the utility of this simple strategy. Large Stokes shifts have been achieved in solid thin-films which show a range of emitted light from blue to orange. The synthesized compounds have been used as biocompatible fluorophores in cell bioimaging. PMID:26991893

  12. Enhancement of a catalysis-based fluorometric detection method for palladium through rational fine-tuning of the palladium species.

    PubMed

    Garner, Amanda L; Song, Fengling; Koide, Kazunori

    2009-04-15

    Metal analyses in chemistry, materials science, and environmental science are currently performed using techniques such as inductively coupled plasma mass spectrometry and X-ray fluorescence, which require expensive instrumentation and are not high-throughput. Although fluorescent probes are known for their sensitivity and specificity and are amenable to high-throughput analyses, the robustness of such analyses are typically limited due to their binding-based nature. Herein we report an improvement of our previously reported catalysis-based fluorescent probe for palladium by rationally fine-tuning the redox and coordination chemistries of the palladium species involved in the O-deallylation reaction. This method now rivals current analytical methods with respect to sensitivity. We demonstrate palladium detection in various active pharmaceutical ingredients, spent catalytic converter materials, and a metal scavenger resin. Thus, fluorescent methods may have the potential for substituting the current instrument-intensive techniques. PMID:19317401

  13. Fine-tuning the onset of myogenesis by homeobox proteins that interact with the Myf5 limb enhancer

    PubMed Central

    Daubas, Philippe; Duval, Nathalie; Bajard, Lola; Langa Vives, Francina; Robert, Benoît; Mankoo, Baljinder S.; Buckingham, Margaret

    2015-01-01

    ABSTRACT Skeletal myogenesis in vertebrates is initiated at different sites of skeletal muscle formation during development, by activation of specific control elements of the myogenic regulatory genes. In the mouse embryo, Myf5 is the first myogenic determination gene to be expressed and its spatiotemporal regulation requires multiple enhancer sequences, extending over 120 kb upstream of the Mrf4-Myf5 locus. An enhancer, located at −57/−58 kb from Myf5, is responsible for its activation in myogenic cells derived from the hypaxial domain of the somite, that will form limb muscles. Pax3 and Six1/4 transcription factors are essential activators of this enhancer, acting on a 145-bp core element. Myogenic progenitor cells that will form the future muscle masses of the limbs express the factors necessary for Myf5 activation when they delaminate from the hypaxial dermomyotome and migrate into the forelimb bud, however they do not activate Myf5 and the myogenic programme until they have populated the prospective muscle masses. We show that Msx1 and Meox2 homeodomain-containing transcription factors bind in vitro and in vivo to specific sites in the 145-bp element, and are implicated in fine-tuning activation of Myf5 in the forelimb. Msx1, when bound between Pax and Six sites, prevents the binding of these key activators, thus inhibiting transcription of Myf5 and consequent premature myogenic differentiation. Meox2 is required for Myf5 activation at the onset of myogenesis via direct binding to other homeodomain sites in this sequence. Thus, these homeodomain factors, acting in addition to Pax3 and Six1/4, fine-tune the entry of progenitor cells into myogenesis at early stages of forelimb development. PMID:26538636

  14. Fine-tuning the onset of myogenesis by homeobox proteins that interact with the Myf5 limb enhancer.

    PubMed

    Daubas, Philippe; Duval, Nathalie; Bajard, Lola; Langa Vives, Francina; Robert, Benoît; Mankoo, Baljinder S; Buckingham, Margaret

    2015-01-01

    Skeletal myogenesis in vertebrates is initiated at different sites of skeletal muscle formation during development, by activation of specific control elements of the myogenic regulatory genes. In the mouse embryo, Myf5 is the first myogenic determination gene to be expressed and its spatiotemporal regulation requires multiple enhancer sequences, extending over 120 kb upstream of the Mrf4-Myf5 locus. An enhancer, located at -57/-58 kb from Myf5, is responsible for its activation in myogenic cells derived from the hypaxial domain of the somite, that will form limb muscles. Pax3 and Six1/4 transcription factors are essential activators of this enhancer, acting on a 145-bp core element. Myogenic progenitor cells that will form the future muscle masses of the limbs express the factors necessary for Myf5 activation when they delaminate from the hypaxial dermomyotome and migrate into the forelimb bud, however they do not activate Myf5 and the myogenic programme until they have populated the prospective muscle masses. We show that Msx1 and Meox2 homeodomain-containing transcription factors bind in vitro and in vivo to specific sites in the 145-bp element, and are implicated in fine-tuning activation of Myf5 in the forelimb. Msx1, when bound between Pax and Six sites, prevents the binding of these key activators, thus inhibiting transcription of Myf5 and consequent premature myogenic differentiation. Meox2 is required for Myf5 activation at the onset of myogenesis via direct binding to other homeodomain sites in this sequence. Thus, these homeodomain factors, acting in addition to Pax3 and Six1/4, fine-tune the entry of progenitor cells into myogenesis at early stages of forelimb development. PMID:26538636

  15. Remote Electronic Effects by Ether Protecting Groups Fine-Tune Glycosyl Donor Reactivity.

    PubMed

    Heuckendorff, Mads; Poulsen, Lulu Teressa; Jensen, Henrik H

    2016-06-17

    It was established that para-substituted benzyl ether protecting groups affect the reactivity of glycosyl donors of the thioglycoside type with the N-iodosuccinimide/triflic acid promoter system. Having electron donating p-methoxybenzyl ether (PMB) groups increased the reactivity of the donor in comparison to having electron withdrawing p-chloro (PClB) or p-cyanobenzyl ether (PCNB) protecting groups, which decreased the reactivity of the glycosyl donor relative to the parent benzyl ether (Bn) protected glycosyl donor. These findings were used to perform the first armed-disarmed coupling between two benzylated glucosyl donors by tuning their reactivity. In addition, the present work describes a highly efficient palladium catalyzed multiple cyanation and methoxylation of p-chlorobenzyl protected thioglycosides. The results of this paper regarding both the different electron withdrawing properties of various benzyl ethers and the efficient and multiple protecting group transformations are applicable in general organic chemistry and not restricted to carbohydrate chemistry. PMID:27224456

  16. Fine frequency tuning in sum-frequency generation of continuous-wave single-frequency coherent light at 252 nm with dual-wavelength enhancement.

    PubMed

    Kumagai, Hiroshi

    2007-01-01

    Fine frequency tuning of the deep-ultraviolet single-mode coherent light at 252 nm was conducted through the PID feedback system automatically by changing the temperature of a beta-BaB(2)O(4) (BBO) crystal in a doubly resonant external cavity for the sum-frequency mixing of 373 and 780 nm light. The temperature-dependent frequency tuning rate is 19.3 MHzK(-1), which is sufficiently fine to realize the laser cooling of neutral silicon atoms because the natural width of the laser cooling transition is 28.8 MHz. PMID:17167584

  17. Fine-Tuning of the Actin Cytoskeleton and Cell Adhesion During Drosophila Development by the Unconventional Guanine Nucleotide Exchange Factors Myoblast City and Sponge

    PubMed Central

    Biersmith, Bridget; Wang, Zong-Heng; Geisbrecht, Erika R.

    2015-01-01

    The evolutionarily conserved Dock proteins function as unconventional guanine nucleotide exchange factors (GEFs). Upon binding to engulfment and cell motility (ELMO) proteins, Dock–ELMO complexes activate the Rho family of small GTPases to mediate a diverse array of biological processes, including cell motility, apoptotic cell clearance, and axon guidance. Overlapping expression patterns and functional redundancy among the 11 vertebrate Dock family members, which are subdivided into four families (Dock A, B, C, and D), complicate genetic analysis. In both vertebrate and invertebrate systems, the actin dynamics regulator, Rac, is the target GTPase of the Dock-A subfamily. However, it remains unclear whether Rac or Rap1 are the in vivo downstream GTPases of the Dock-B subfamily. Drosophila melanogaster is an excellent genetic model organism for understanding Dock protein function as its genome encodes one ortholog per subfamily: Myoblast city (Mbc; Dock A) and Sponge (Spg; Dock B). Here we show that the roles of Spg and Mbc are not redundant in the Drosophila somatic muscle or the dorsal vessel. Moreover, we confirm the in vivo role of Mbc upstream of Rac and provide evidence that Spg functions in concert with Rap1, possibly to regulate aspects of cell adhesion. Together these data show that Mbc and Spg can have different downstream GTPase targets. Our findings predict that the ability to regulate downstream GTPases is dependent on cellular context and allows for the fine-tuning of actin cytoskeletal or cell adhesion events in biological processes that undergo cell morphogenesis. PMID:25908317

  18. Rational Diversification of a Promoter Providing Fine-Tuned Expression and Orthogonal Regulation for Synthetic Biology

    PubMed Central

    Blount, Benjamin A.; Weenink, Tim; Vasylechko, Serge; Ellis, Tom

    2012-01-01

    Yeast is an ideal organism for the development and application of synthetic biology, yet there remain relatively few well-characterised biological parts suitable for precise engineering of this chassis. In order to address this current need, we present here a strategy that takes a single biological part, a promoter, and re-engineers it to produce a fine-graded output range promoter library and new regulated promoters desirable for orthogonal synthetic biology applications. A highly constitutive Saccharomyces cerevisiae promoter, PFY1p, was identified by bioinformatic approaches, characterised in vivo and diversified at its core sequence to create a 36-member promoter library. TetR regulation was introduced into PFY1p to create a synthetic inducible promoter (iPFY1p) that functions in an inverter device. Orthogonal and scalable regulation of synthetic promoters was then demonstrated for the first time using customisable Transcription Activator-Like Effectors (TALEs) modified and designed to act as orthogonal repressors for specific PFY1-based promoters. The ability to diversify a promoter at its core sequences and then independently target Transcription Activator-Like Orthogonal Repressors (TALORs) to virtually any of these sequences shows great promise toward the design and construction of future synthetic gene networks that encode complex “multi-wire” logic functions. PMID:22442681

  19. Guided wave phased array sensor tuning for improved defect detection and characterization

    NASA Astrophysics Data System (ADS)

    Philtron, Jason H.; Rose, Joseph L.

    2014-03-01

    Ultrasonic guided waves are finding increased use in a variety of Nondestructive Evaluation and Structural Health Monitoring applications due to their efficiency in defect detection using a sensor at a single location to inspect a large area of a structure and an ability to inspect hidden and coated areas for example. With a thorough understanding of guided wave mechanics, researchers can predict which guided wave modes will have a high probability of success in a particular nondestructive evaluation application. For example, in a sample problem presented here to access bond integrity, researchers may choose to use a guided wave mode which has high in-plane displacement, stress, or other feature at the interface. However, since material properties used for modeling work may not be precise for the development of dispersion curves, in many cases guided wave mode and frequency selection should be adjusted for increased inspection efficiency in the field. In this work, a phased array comb transducer is used to sweep over phase velocity - frequency space to tune mode excitation for improved defect characterization performance. A thin polycarbonate layer bonded to a thick metal plate is considered with a contaminated surface prior to bonding. Physicallybased features are used to correlate wave signals with defect detection. Features assessed include arrival time and the frequency of maximum amplitude. A pseudo C-scan plot is presented which can be used to simplify data analysis. Excellent results are obtained.

  20. Over 11% Efficiency in Tandem Polymer Solar Cells Featured by a Low-Band-Gap Polymer with Fine-Tuned Properties.

    PubMed

    Zheng, Zhong; Zhang, Shaoqing; Zhang, Jianqi; Qin, Yunpeng; Li, Wanning; Yu, Runnan; Wei, Zhixiang; Hou, Jianhui

    2016-07-01

    Highly efficient polymer solar cells with tandem structure are fabricated by using two excellent photovoltaic polymers and a highly transparent intermediate recombination layer. Power conversion efficiencies over 11% can be realized featured by a low-band-gap polymer with fine-tuned properties. PMID:27136384

  1. Tomato Yield Heterosis Is Triggered by a Dosage Sensitivity of the Florigen Pathway That Fine-Tunes Shoot Architecture

    PubMed Central

    Jiang, Ke; Liberatore, Katie L.; Park, Soon Ju; Alvarez, John P.; Lippman, Zachary B.

    2013-01-01

    The superiority of hybrids has long been exploited in agriculture, and although many models explaining “heterosis” have been put forth, direct empirical support is limited. Particularly elusive have been cases of heterozygosity for single gene mutations causing heterosis under a genetic model known as overdominance. In tomato (Solanum lycopersicum), plants carrying mutations in SINGLE FLOWER TRUSS (SFT) encoding the flowering hormone florigen are severely delayed in flowering, become extremely large, and produce few flowers and fruits, but when heterozygous, yields are dramatically increased. Curiously, this overdominance is evident only in the background of “determinate” plants, in which the continuous production of side shoots and inflorescences gradually halts due to a defect in the flowering repressor SELF PRUNING (SP). How sp facilitates sft overdominance is unclear, but is thought to relate to the opposing functions these genes have on flowering time and shoot architecture. We show that sft mutant heterozygosity (sft/+) causes weak semi-dominant delays in flowering of both primary and side shoots. Using transcriptome sequencing of shoot meristems, we demonstrate that this delay begins before seedling meristems become reproductive, followed by delays in subsequent side shoot meristems that, in turn, postpone the arrest of shoot and inflorescence production. Reducing SFT levels in sp plants by artificial microRNAs recapitulates the dose-dependent modification of shoot and inflorescence production of sft/+ heterozygotes, confirming that fine-tuning levels of functional SFT transcripts provides a foundation for higher yields. Finally, we show that although flowering delays by florigen mutant heterozygosity are conserved in Arabidopsis, increased yield is not, likely because cyclical flowering is absent. We suggest sft heterozygosity triggers a yield improvement by optimizing plant architecture via its dosage response in the florigen pathway. Exploiting

  2. Fine-tuning of CD8(+) T-cell effector functions by targeting the 2B4-CD48 interaction.

    PubMed

    Lissina, Anna; Ambrozak, David R; Boswell, Kristin L; Yang, Wenjing; Boritz, Eli; Wakabayashi, Yoshiyuki; Iglesias, Maria C; Hashimoto, Masao; Takiguchi, Masafumi; Haddad, Elias; Douek, Daniel C; Zhu, Jun; Koup, Richard A; Yamamoto, Takuya; Appay, Victor

    2016-07-01

    Polyfunctionality and cytotoxic activity dictate CD8(+) T-cell efficacy in the eradication of infected and malignant cells. The induction of these effector functions depends on the specific interaction between the T-cell receptor (TCR) and its cognate peptide-MHC class I complex, in addition to signals provided by co-stimulatory or co-inhibitory receptors, which can further regulate these functions. Among these receptors, the role of 2B4 is contested, as it has been described as either co-stimulatory or co-inhibitory in modulating T-cell functions. We therefore combined functional, transcriptional and epigenetic approaches to further characterize the impact of disrupting the interaction of 2B4 with its ligand CD48, on the activity of human effector CD8(+) T-cell clones. In this setting, we show that the 2B4-CD48 axis is involved in the fine-tuning of CD8(+) T-cell effector function upon antigenic stimulation. Blocking this interaction resulted in reduced CD8(+) T-cell clone-mediated cytolytic activity, together with a subtle drop in the expression of genes involved in effector function regulation. Our results also imply a variable contribution of the 2B4-CD48 interaction to the modulation of CD8(+) T-cell functional properties, potentially linked to intrinsic levels of T-bet expression and TCR avidity. The present study thus provides further insights into the role of the 2B4-CD48 interaction in the fine regulation of CD8(+) T-cell effector function upon antigenic stimulation. PMID:26860368

  3. Su(fu) switches Rdx functions to fine-tune hedgehog signaling in the Drosophila wing disk.

    PubMed

    Seong, Ki-Hyeon; Ishii, Shunsuke

    2013-01-01

    Hedgehog (Hh) signaling plays a central role in pattern formation by regulating transcription factor Cubitus interruptus (Ci). Previously, Roadkill (Rdx, also called HIB) was shown to inhibit Ci activity by two distinct mechanisms, depending on the Hh signal strength (Seong et al. 2010, PLoS One 5, e15365). In the anterior region abutting the anterior/posterior (A/P) boundary of the wing disk, where cells receive a strong Hh signal, Rdx blocks the nuclear entry of Ci-155. In contrast, in the region farther from the A/P boundary, where cells receive moderate levels of Hh, Rdx induces Ci-155 degradation in the nucleus. Here, we report that Suppressor of fused, Su(fu), causes the Rdx switch between mechanisms. A strong Hh signal induces rdx expression and suppresses su(fu) expression, whereas moderate levels of Hh induce moderate levels of rdx expression and high levels of su(fu) expression. Rdx blocks entry of Ci-155 into the nucleus in the absence of Su(fu) and Rdx induces the degradation of Ci-155 in the nucleus in the presence of a threshold level of Su(fu). Thus, the Su(fu)-induced switch between the dual actions of Rdx in response to the Hh signal strength plays a role in fine-tuning Hh signaling. PMID:23216924

  4. Fine-tuning the stimulation of MLL1 methyltransferase activity by a histone H3-based peptide mimetic

    SciTech Connect

    Avdic, Vanja; Zhang, Pamela; Lanouette, Sylvain; Voronova, Anastassia; Skerjanc, Ilona; Couture, Jean-Francois

    2011-08-24

    The SET1 family of methyltransferases carries out the bulk of histone H3 Lys-4 methylation in vivo. One of the common features of this family is the regulation of their methyltransferase activity by a tripartite complex composed of WDR5, RbBP5, and Ash2L. To selectively probe the role of the SET1 family of methyltransferases, we have developed a library of histone H3 peptide mimetics and report herein the characterization of an N{alpha} acetylated form of histone H3 peptide (N{alpha}H3). Binding and inhibition studies reveal that the addition of an acetyl moiety to the N terminus of histone H3 significantly enhances its binding to WDR5 and prevents the stimulation of MLL1 methyltransferase activity by the WDR5-RbBP5-Ash2L complex. The crystal structure of N{alpha}H3 in complex with WDR5 reveals that a high-affinity hydrophobic pocket accommodates the binding of the acetyl moiety. These results provide the structural basis to control WDR5-RbBP5-Ash2L-MLL1 activity and a tool to manipulate stem cell differentiation programs.-Avdic, V., Zhang, P., Lanouette, S., Voronova, A., Skerjanc, I., Couture, J.-F. Fine-tuning the stimulation of MLL1 methyltransferase activity by a histone H3-based peptide mimetic.

  5. 5-Azacytidine-induced Protein 2 (AZI2) Regulates Bone Mass by Fine-tuning Osteoclast Survival*

    PubMed Central

    Maruyama, Kenta; Fukasaka, Masahiro; Uematsu, Satoshi; Takeuchi, Osamu; Kondo, Takeshi; Saitoh, Tatsuya; Martino, Mikaël M.; Akira, Shizuo

    2015-01-01

    5-Azacytidine-induced protein 2 (AZI2) is a TNF receptor (TNFR)-associated factor family member-associated NF-κB activator-binding kinase 1-binding protein that regulates the production of IFNs. A previous in vitro study showed that AZI2 is involved in dendritic cell differentiation. However, the roles of AZI2 in immunity and its pleiotropic functions are unknown in vivo. Here we report that AZI2 knock-out mice exhibit normal dendritic cell differentiation in vivo. However, we found that adult AZI2 knock-out mice have severe osteoporosis due to increased osteoclast longevity. We revealed that the higher longevity of AZI2-deficient osteoclasts is due to an augmented activation of proto-oncogene tyrosine-protein kinase Src (c-Src), which is a critical player in osteoclast survival. We found that AZI2 inhibits c-Src activity by regulating the activation of heat shock protein 90 (Hsp90), a chaperone involved in c-Src dephosphorylation. Furthermore, we demonstrated that AZI2 indirectly inhibits c-Src by interacting with the Hsp90 co-chaperone Cdc37. Strikingly, administration of a c-Src inhibitor markedly prevented bone loss in AZI2 knock-out mice. Together, these findings indicate that AZI2 regulates bone mass by fine-tuning osteoclast survival. PMID:25691576

  6. 5-Azacytidine-induced protein 2 (AZI2) regulates bone mass by fine-tuning osteoclast survival.

    PubMed

    Maruyama, Kenta; Fukasaka, Masahiro; Uematsu, Satoshi; Takeuchi, Osamu; Kondo, Takeshi; Saitoh, Tatsuya; Martino, Mikaël M; Akira, Shizuo

    2015-04-10

    5-Azacytidine-induced protein 2 (AZI2) is a TNF receptor (TNFR)-associated factor family member-associated NF-κB activator-binding kinase 1-binding protein that regulates the production of IFNs. A previous in vitro study showed that AZI2 is involved in dendritic cell differentiation. However, the roles of AZI2 in immunity and its pleiotropic functions are unknown in vivo. Here we report that AZI2 knock-out mice exhibit normal dendritic cell differentiation in vivo. However, we found that adult AZI2 knock-out mice have severe osteoporosis due to increased osteoclast longevity. We revealed that the higher longevity of AZI2-deficient osteoclasts is due to an augmented activation of proto-oncogene tyrosine-protein kinase Src (c-Src), which is a critical player in osteoclast survival. We found that AZI2 inhibits c-Src activity by regulating the activation of heat shock protein 90 (Hsp90), a chaperone involved in c-Src dephosphorylation. Furthermore, we demonstrated that AZI2 indirectly inhibits c-Src by interacting with the Hsp90 co-chaperone Cdc37. Strikingly, administration of a c-Src inhibitor markedly prevented bone loss in AZI2 knock-out mice. Together, these findings indicate that AZI2 regulates bone mass by fine-tuning osteoclast survival. PMID:25691576

  7. Fine-tuning of DDES and IDDES formulations to the k-ω shear stress transport model

    NASA Astrophysics Data System (ADS)

    Gritskevich, M. S.; Garbaruk, A. V.; Menter, F. R.

    2013-06-01

    Modifications are proposed of two recently developed hybrid CFD (computational fluid dynamics) strategies, Delayed Detached Eddy Simulation (DDES), and DDES with Improved wall-modeling capability (IDDES). The modifications are aimed at fine-tuning of these approaches to the k-ω SST (shear stress transport) background RANS (Reynolds-averaged Navier-Stokes) model. The first one includes recalibrated empirical constants in the shielding function of the Spalart-Allmaras (SA) based DDES which are shown to be suboptimal (not providing a needed level of elimination of the Model Stress Depletion (MSD)) for the SST-based DDES model. For the SST-IDDES variant, in addition to that, a simplification of the original SA-based formulation is proposed, which does not cause any visible degradation of the model performance. Both modifications are extensively tested on a range of attached and separated flows (developed channel, backward-facing step, periodic hills, wall-mounted hump, and hydrofoil with trailing edge separation).

  8. Seam tracking with adaptive image capture for fine-tuning of a high power laser welding process

    NASA Astrophysics Data System (ADS)

    Lahdenoja, Olli; Säntti, Tero; Laiho, Mika; Paasio, Ari; Poikonen, Jonne K.

    2015-02-01

    This paper presents the development of methods for real-time fine-tuning of a high power laser welding process of thick steel by using a compact smart camera system. When performing welding in butt-joint configuration, the laser beam's location needs to be adjusted exactly according to the seam line in order to allow the injected energy to be absorbed uniformly into both steel sheets. In this paper, on-line extraction of seam parameters is targeted by taking advantage of a combination of dynamic image intensity compression, image segmentation with a focal-plane processor ASIC, and Hough transform on an associated FPGA. Additional filtering of Hough line candidates based on temporal windowing is further applied to reduce unrealistic frame-to-frame tracking variations. The proposed methods are implemented in Matlab by using image data captured with adaptive integration time. The simulations are performed in a hardware oriented way to allow real-time implementation of the algorithms on the smart camera system.

  9. miR-17-92 fine-tunes MYC expression and function to ensure optimal B cell lymphoma growth

    PubMed Central

    Mihailovich, Marija; Bremang, Michael; Spadotto, Valeria; Musiani, Daniele; Vitale, Elena; Varano, Gabriele; Zambelli, Federico; Mancuso, Francesco M.; Cairns, David A.; Pavesi, Giulio; Casola, Stefano; Bonaldi, Tiziana

    2015-01-01

    The synergism between c-MYC and miR-17-19b, a truncated version of the miR-17-92 cluster, is well-documented during tumor initiation. However, little is known about miR-17-19b function in established cancers. Here we investigate the role of miR-17-19b in c-MYC-driven lymphomas by integrating SILAC-based quantitative proteomics, transcriptomics and 3′ untranslated region (UTR) analysis upon miR-17-19b overexpression. We identify over one hundred miR-17-19b targets, of which 40% are co-regulated by c-MYC. Downregulation of a new miR-17/20 target, checkpoint kinase 2 (Chek2), increases the recruitment of HuR to c-MYC transcripts, resulting in the inhibition of c-MYC translation and thus interfering with in vivo tumor growth. Hence, in established lymphomas, miR-17-19b fine-tunes c-MYC activity through a tight control of its function and expression, ultimately ensuring cancer cell homeostasis. Our data highlight the plasticity of miRNA function, reflecting changes in the mRNA landscape and 3′ UTR shortening at different stages of tumorigenesis. PMID:26555894

  10. Fine tuning the color-transition temperature of thermoreversible polydiacetylene/zinc oxide nanocomposites: The effect of photopolymerization time.

    PubMed

    Traiphol, Nisanart; Faisadcha, Kunruethai; Potai, Ruttayapon; Traiphol, Rakchart

    2015-02-01

    An ability to control the thermochromic behaviors of polydiacetylene (PDA)-based materials is very important for their utilization. Recently, our group has developed the PDA/zinc oxide (ZnO) nanocomposites, which exhibit reversible thermochromism (Traiphol et al., 2011). In this study, we present our continuation work demonstrating a rather simple method for fine tuning their color-transition temperature. The PDA/ZnO nanocomposites are prepared by varying photopolymerization time, which in turn affects the length of PDA conjugated backbone. We have found that the increase of photopolymerization time from 1 to 120min results in systematically decrease of the color-transition temperature from about 85 to 40°C. These PDA/ZnO nanocomposites still exhibit reversible thermochromism. The PDA/ZnO nanocomposites embedded in polyvinyl alcohol films show two-step color-transition processes, the reversible blue to purple and then irreversible purple to orange. Interestingly, the increase of photopolymerization time causes an increase of the irreversible color-transition temperature. Our method is quite simple and cheap, which can provide a library of PDA-based materials with controllable color-transition temperature. PMID:25463181

  11. Comparative phosphoproteome profiling reveals a function of the STN8 kinase in fine-tuning of cyclic electron flow (CEF)

    PubMed Central

    Reiland, Sonja; Finazzi, Giovanni; Endler, Anne; Willig, Adrian; Baerenfaller, Katja; Grossmann, Jonas; Gerrits, Bertran; Rutishauser, Dorothea; Gruissem, Wilhelm; Rochaix, Jean-David; Baginsky, Sacha

    2011-01-01

    Important aspects of photosynthetic electron transport efficiency in chloroplasts are controlled by protein phosphorylation. Two thylakoid-associated kinases, STN7 and STN8, have distinct roles in short- and long-term photosynthetic acclimation to changes in light quality and quantity. Although some substrates of STN7 and STN8 are known, the complexity of this regulatory kinase system implies that currently unknown substrates connect photosynthetic performance with the regulation of metabolic and regulatory functions. We performed an unbiased phosphoproteome-wide screen with Arabidopsis WT and stn8 mutant plants to identify unique STN8 targets. The phosphorylation status of STN7 was not affected in stn8, indicating that kinases other than STN8 phosphorylate STN7 under standard growth conditions. Among several putative STN8 substrates, PGRL1-A is of particular importance because of its possible role in the modulation of cyclic electron transfer. The STN8 phosphorylation site on PGRL1-A is absent in both monocotyledonous plants and algae. In dicots, spectroscopic measurements with Arabidopsis WT, stn7, stn8, and stn7/stn8 double-mutant plants indicate a STN8-mediated slowing down of the transition from cyclic to linear electron flow at the onset of illumination. This finding suggests a possible link between protein phosphorylation by STN8 and fine-tuning of cyclic electron flow during this critical step of photosynthesis, when the carbon assimilation is not commensurate to the electron flow capacity of the chloroplast. PMID:21768351

  12. The crystal structure of the global anaerobic transcriptional regulator FNR explains its extremely fine-tuned monomer-dimer equilibrium.

    PubMed

    Volbeda, Anne; Darnault, Claudine; Renoux, Oriane; Nicolet, Yvain; Fontecilla-Camps, Juan C

    2015-12-01

    The structure of the dimeric holo-fumarate and nitrate reduction regulator (FNR) from Aliivibrio fischeri has been solved at 2.65 Å resolution. FNR globally controls the transition between anaerobic and aerobic respiration in facultative anaerobes through the assembly/degradation of its oxygen-sensitive [4Fe-4S] cluster. In the absence of O2, FNR forms a dimer and specifically binds to DNA, whereas in its presence, the cluster is degraded causing FNR monomerization and DNA dissociation. We have used our crystal structure and the information previously gathered from numerous FNR variants to propose that this process is governed by extremely fine-tuned interactions, mediated by two salt bridges near the amino-terminal cluster-binding domain and an "imperfect" coiled-coil dimer interface. [4Fe-4S] to [2Fe-2S] cluster degradation propagates a conformational signal that indirectly causes monomerization by disrupting the first of these interactions and unleashing the "unzipping" of the FNR dimer in the direction of the carboxyl-terminal DNA binding domain. PMID:26665177

  13. Probing conformational changes in lipoxygenases upon membrane binding: fine-tuning by the active site inhibitor ETYA.

    PubMed

    Di Venere, Almerinda; Nicolai, Eleonora; Ivanov, Igor; Dainese, Enrico; Adel, Susan; Angelucci, B C; Kuhn, Hartmut; Maccarrone, Mauro; Mei, Giampiero

    2014-01-01

    Lipoxygenases (LOXs) are lipid-peroxidizing enzymes that are involved in the metabolism of polyunsaturated fatty acids. Their biological activity includes a membrane binding process whose molecular details are not completely understood. The mechanism of enzyme-membrane interactions is thought to involve conformational changes at the level of the protein tertiary structure, and the extent of such alterations depends on the degree of structural flexibility of the different LOX isoforms. In this study, we have tested the resilience properties of a plant and a mammalian LOX, by using high pressure fluorescence measurements at different temperatures. The binding of LOXs to the lipid bilayer has been characterized using both large and giant unilamellar vesicles and electron transfer particles (inner mitochondrial membranes) as model membranes. The data indicate that the degree of LOXs' flexibility is strictly dependent on the two distinct N- and C-terminal domains that characterize the 3D structure of these enzymes. Furthermore, they demonstrate that increasing the rigidity of protein scaffolding by the presence of an active site ligand impairs the membrane binding ability of LOXs. These findings provide evidence that the amphitropic nature of LOXs is finely tuned by the interaction of the substrate with the residues of the active site, suggesting new strategies for the design of enzyme inhibitors. PMID:24012824

  14. Fine tuning of the pH-sensitivity of laponite-doxorubicin nanohybrids by polyelectrolyte multilayer coating.

    PubMed

    Xiao, Shili; Castro, Rita; Maciel, Dina; Gonçalves, Mara; Shi, Xiangyang; Rodrigues, João; Tomás, Helena

    2016-03-01

    Despite the wide research done in the field, the development of advanced drug delivery systems with improved drug delivery properties and effective anticancer capability still remains a great challenge. Based on previous work that showed the potentialities of the nanoclay Laponite as a pH-sensitive doxorubicin (Dox) delivery vehicle, herein we report a simple method to modulate its extent of drug release at different pH values. This was achieved by alternate deposition of cationic poly(allylamine) hydrochloride and anionic poly(sodium styrene sulfonate) (PAH/PSS) polyelectrolytes over the surface of Dox-loaded Laponite nanoparticles using the electrostatic layer-by-layer (LbL) self-assembly approach. The successful formation of polyelectrolyte multilayer-coated Dox/Laponite systems was confirmed by Dynamic Light Scattering and zeta potential measurements. Systematic studies were performed to evaluate their drug release profiles and anticancer efficiency. Our results showed that the presence of the polyelectrolyte multilayers improved the sustained release properties of Laponite and allowed a fine tuning of the extension of drug release at neutral and acidic pH values. The cytotoxicity presented by polyelectrolyte multilayer-coated Dox/Laponite systems towards MCF-7 cells was in accordance with the drug delivery profiles. Furthermore, cellular uptake studies revealed that polyelectrolyte multilayer-coated Dox/Laponite nanoparticles can be effectively internalized by cells conducting to Dox accumulation in cell nucleus. PMID:26706540

  15. Fine-tuning synaptic plasticity by modulation of Ca(V)2.1 channels with Ca2+ sensor proteins.

    PubMed

    Leal, Karina; Mochida, Sumiko; Scheuer, Todd; Catterall, William A

    2012-10-16

    Modulation of P/Q-type Ca(2+) currents through presynaptic voltage-gated calcium channels (Ca(V)2.1) by binding of Ca(2+)/calmodulin contributes to short-term synaptic plasticity. Ca(2+)-binding protein-1 (CaBP1) and Visinin-like protein-2 (VILIP-2) are neurospecific calmodulin-like Ca(2+) sensor proteins that differentially modulate Ca(V)2.1 channels, but how they contribute to short-term synaptic plasticity is unknown. Here, we show that activity-dependent modulation of presynaptic Ca(V)2.1 channels by CaBP1 and VILIP-2 has opposing effects on short-term synaptic plasticity in superior cervical ganglion neurons. Expression of CaBP1, which blocks Ca(2+)-dependent facilitation of P/Q-type Ca(2+) current, markedly reduced facilitation of synaptic transmission. VILIP-2, which blocks Ca(2+)-dependent inactivation of P/Q-type Ca(2+) current, reduced synaptic depression and increased facilitation under conditions of high release probability. These results demonstrate that activity-dependent regulation of presynaptic Ca(V)2.1 channels by differentially expressed Ca(2+) sensor proteins can fine-tune synaptic responses to trains of action potentials and thereby contribute to the diversity of short-term synaptic plasticity. PMID:23027954

  16. Resistin reinforces interferon λ-3 to eliminate hepatitis C virus with fine-tuning from RETN single-nucleotide polymorphisms

    PubMed Central

    Chang, Ming-Ling; Liang, Kung-Hao; Ku, Cheng-Lung; Lo, Chia-Chi; Cheng, Ya-Ting; Hsu, Chen-Ming; Yeh, Chau-Ting; Chiu, Cheng-Tang

    2016-01-01

    The effect of resistin (RETN) on the response to anti-HCV therapy remains unclear. A prospective cohort study was performed using 655 consecutive HCV patients, of whom 513 had completed a course of interferon-based therapy. Multivariate and GEE analyses revealed four RETN single-nucleotide polymorphisms (SNPs), rs34861192, rs3219175, rs3745367 and rs1423096, to be synergistically associated with resistin levels. After adjusting for co-factors such as interferon λ-3 (IFNL3)-rs12979860, the resistin level and the hyper-resistinemic genotype at the 4 RETN SNPs were positively and negatively associated with a sustained virological response (SVR), respectively. RETN-rs3745367 was in linkage disequilibrium with IFNL3-rs12979860. Compared to non-SVR patients, SVR patients had higher levels of pre-therapy resistin, primarily originating from intrahepatic lymphocytes, stellate cells, Kupffer cells, hepatic progenitor cells and hepatocytes. This difference diminished over the course of therapy, as only SVR patients exhibited a 24-week post-therapy decrease in resistin. Both resistin and IFNL3 mRNAs were upregulated, but only resistin mRNA was upregulated by recombinant resistin in peripheral blood mononuclear cells with and without hyper-resistinemic genotypes of the 4 RETN SNPs, respectively. Fine-tuned by RETN SNPs, intrahepatic, multi-cellular resistin reinforced IFNL3 in eliminating HCV via immunomodulation to counteract pro-inflammation. These results encourage the development of novel resistin-targeted anti-viral agents. PMID:27477870

  17. Fnr (EtrA) acts as a fine-tuning regulator of anaerobic metabolism in Shewanella oneidensis MR-1

    SciTech Connect

    Cruz-Garza, Claribel; Murray, Alison E.; Rodrigues, Jorge L.M.; Gralnick, Jeffrey A.; McCue, Lee Ann; Romine, Margaret F.; Loffler, F. E.; Tiedje, James M.

    2011-03-30

    EtrA in Shewanella oneidensis MR-1, a model organism for study of adaptation to varied redox niches, shares 73.6% and 50.8% amino acid sequence identity with the oxygen-sensing regulators Fnr in E. coli and Anr in Pseudomonas aeruginosa, respectively; however, its regulatory role of anaerobic metabolism in Shewanella spp. is not well understood. The expression of the nap genes, nrfA, cymA and hcp was significantly reduced in etrA deletion mutant EtrA7-1; however, limited anaerobic growth and nitrate reduction occurred, suggesting that multiple regulators control nitrate reduction in this strain. Dimethyl sulfoxide (DMSO) and fumarate reductase gene expression was down regulated at least 2-fold and the EtrA7-1 mutant grew poorly with fumarate and dimethyl sulfoxide (DMSO), suggesting both respiratory pathways are under EtrA control. Transcript analysis further suggested a role of EtrA in prophage activation and down regulation of genes implicated in aerobic metabolism. In contrast to previous studies that attributed a minor regulatory role to EtrA in Shewanella spp., this study demonstrates that EtrA acts as a global transcriptional regulator and confers physiological advantages to strain MR-1 under certain growth conditions. In conjunction with other regulators, EtrA fine-tunes the expression of genes involved in anaerobic metabolism in S. oneidensis strain MR-1.

  18. The crystal structure of the global anaerobic transcriptional regulator FNR explains its extremely fine-tuned monomer-dimer equilibrium

    PubMed Central

    Volbeda, Anne; Darnault, Claudine; Renoux, Oriane; Nicolet, Yvain; Fontecilla-Camps, Juan C.

    2015-01-01

    The structure of the dimeric holo–fumarate and nitrate reduction regulator (FNR) from Aliivibrio fischeri has been solved at 2.65 Å resolution. FNR globally controls the transition between anaerobic and aerobic respiration in facultative anaerobes through the assembly/degradation of its oxygen-sensitive [4Fe-4S] cluster. In the absence of O2, FNR forms a dimer and specifically binds to DNA, whereas in its presence, the cluster is degraded causing FNR monomerization and DNA dissociation. We have used our crystal structure and the information previously gathered from numerous FNR variants to propose that this process is governed by extremely fine-tuned interactions, mediated by two salt bridges near the amino-terminal cluster-binding domain and an “imperfect” coiled-coil dimer interface. [4Fe-4S] to [2Fe-2S] cluster degradation propagates a conformational signal that indirectly causes monomerization by disrupting the first of these interactions and unleashing the “unzipping” of the FNR dimer in the direction of the carboxyl-terminal DNA binding domain. PMID:26665177

  19. Rate of hydrolysis in ATP synthase is fine-tuned by α-subunit motif controlling active site conformation.

    PubMed

    Beke-Somfai, Tamás; Lincoln, Per; Nordén, Bengt

    2013-02-01

    Computer-designed artificial enzymes will require precise understanding of how conformation of active sites may control barrier heights of key transition states, including dependence on structure and dynamics at larger molecular scale. F(o)F(1) ATP synthase is interesting as a model system: a delicate molecular machine synthesizing or hydrolyzing ATP using a rotary motor. Isolated F(1) performs hydrolysis with a rate very sensitive to ATP concentration. Experimental and theoretical results show that, at low ATP concentrations, ATP is slowly hydrolyzed in the so-called tight binding site, whereas at higher concentrations, the binding of additional ATP molecules induces rotation of the central γ-subunit, thereby forcing the site to transform through subtle conformational changes into a loose binding site in which hydrolysis occurs faster. How the 1-Å-scale rearrangements are controlled is not yet fully understood. By a combination of theoretical approaches, we address how large macromolecular rearrangements may manipulate the active site and how the reaction rate changes with active site conformation. Simulations reveal that, in response to γ-subunit position, the active site conformation is fine-tuned mainly by small α-subunit changes. Quantum mechanics-based results confirm that the sub-Ångström gradual changes between tight and loose binding site structures dramatically alter the hydrolysis rate. PMID:23345443

  20. Large-Scale Phenomics Identifies Primary and Fine-Tuning Roles for CRKs in Responses Related to Oxidative Stress

    PubMed Central

    Rayapuram, Channabasavangowda; Idänheimo, Niina; Hunter, Kerri; Kimura, Sachie; Merilo, Ebe; Vaattovaara, Aleksia; Oracz, Krystyna; Kaufholdt, David; Pallon, Andres; Anggoro, Damar Tri; Glów, Dawid; Lowe, Jennifer; Zhou, Ji; Mohammadi, Omid; Puukko, Tuomas; Albert, Andreas; Lang, Hans; Ernst, Dieter; Kollist, Hannes; Brosché, Mikael; Durner, Jörg; Borst, Jan Willem; Collinge, David B.; Karpiński, Stanisław; Lyngkjær, Michael F.; Robatzek, Silke; Wrzaczek, Michael; Kangasjärvi, Jaakko

    2015-01-01

    Cysteine-rich receptor-like kinases (CRKs) are transmembrane proteins characterized by the presence of two domains of unknown function 26 (DUF26) in their ectodomain. The CRKs form one of the largest groups of receptor-like protein kinases in plants, but their biological functions have so far remained largely uncharacterized. We conducted a large-scale phenotyping approach of a nearly complete crk T-DNA insertion line collection showing that CRKs control important aspects of plant development and stress adaptation in response to biotic and abiotic stimuli in a non-redundant fashion. In particular, the analysis of reactive oxygen species (ROS)-related stress responses, such as regulation of the stomatal aperture, suggests that CRKs participate in ROS/redox signalling and sensing. CRKs play general and fine-tuning roles in the regulation of stomatal closure induced by microbial and abiotic cues. Despite their great number and high similarity, large-scale phenotyping identified specific functions in diverse processes for many CRKs and indicated that CRK2 and CRK5 play predominant roles in growth regulation and stress adaptation, respectively. As a whole, the CRKs contribute to specificity in ROS signalling. Individual CRKs control distinct responses in an antagonistic fashion suggesting future potential for using CRKs in genetic approaches to improve plant performance and stress tolerance. PMID:26197346

  1. Activation of oxygen-mediating pathway using copper ions: fine-tuning of growth kinetics in gold nanorod overgrowth.

    PubMed

    Liu, Wenqi; Zhang, Hui; Wen, Tao; Yan, Jiao; Hou, Shuai; Shi, Xiaowei; Hu, Zhijian; Ji, Yinglu; Wu, Xiaochun

    2014-10-21

    Growth kinetics plays an important role in the shape control of nanocrystals (NCs). Herein, we presented a unique way to fine-tune the growth kinetics via oxidative etching activated by copper ions. For the overgrowth of gold nanorods (Au NRs), competitive adsorption of dissolved oxygen on rod surface was found to slow down the overgrowth rate. Copper ions were able to remove the adsorbed oxygen species from the Au surface via oxidative etching, thus exposing more reaction sites for Au deposition. In this way, copper ions facilitated the overgrowth process. Furthermore, Cu(2+) rather than Cu(+) acted as the catalyst for the oxidative etching. Comparative study with Ag(+) indicated that Cu(2+) cannot regulate NC shapes via an underpotential deposition mechanism. In contrast, Ag(+) led to the formation of Au tetrahexahedra (THH) and a slight decrease of the growth rate at similar growth conditions. Combining the distinct roles of the two ions enabled elongated THH to be produced. Copper ions activating the O2 pathway suggested that dissolved oxygen has a strong affinity for the Au surface. Moreover, the results of NC-sensitized singlet oxygen ((1)O2) indicated that the absorbed oxygen species on the surface of Au NCs bounded with low-index facets mainly existed in the form of molecular O2. PMID:25244407

  2. All-optical, polarization-insensitive light tuning properties in silver nanorod arrays covered with photoresponsive liquid crystals.

    PubMed

    Si, Guangyuan; Leong, Eunice S P; Jiang, Xiaoxiao; Lv, Jiangtao; Lin, Jiao; Dai, Haitao; Liu, Yan Jun

    2015-05-28

    Active plasmonics has been an interesting and important topic recently. Here we demonstrate the all-optical, polarization-insensitive tunable manipulation of a hybrid system that integrates a silver nanorod array with photoresponsive liquid crystals. The large-area plasmonic nanorod arrays are fabricated by laser interference lithography and ion milling. By covering a layer of photoresponsive liquid crystals, tunable control of plasmon resonance is achieved under an external light pump. The silver nanorod array also enables the homeotropic alignment of the liquid crystals, which makes the all-optical tuning behavior polarization-insensitive. With its advantages of cost-effective fabrication, easy integration, all-optical control, and polarization-insensitivity, the hybrid system could be valuable in many nanophotonic applications. PMID:25758775

  3. Fine Tuning Your Lease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    What is the optimum lease arrangement for the no-till farmer? No-till farmers will many times have more "up front" chemical input costs than a conventional till farmer. Do these differences warrant a different lease arrangement? An easy to use spreadsheet tool was developed to enable a farmer to ...

  4. High Performance All-Polymer Solar Cells by Synergistic Effects of Fine-Tuned Crystallinity and Solvent Annealing.

    PubMed

    Li, Zhaojun; Xu, Xiaofeng; Zhang, Wei; Meng, Xiangyi; Ma, Wei; Yartsev, Arkady; Inganäs, Olle; Andersson, Mats R; Janssen, René A J; Wang, Ergang

    2016-08-31

    Growing interests have been devoted to the design of polymer acceptors as potential replacement for fullerene derivatives for high-performance all polymer solar cells (all-PSCs). One key factor that is limiting the efficiency of all-PSCs is the low fill factor (FF) (normally <0.65), which is strongly correlated with the mobility and film morphology of polymer:polymer blends. In this work, we find a facile method to modulate the crystallinity of the well-known naphthalene diimide (NDI) based polymer N2200, by replacing a certain amount of bithiophene (2T) units in the N2200 backbone by single thiophene (T) units and synthesizing a series of random polymers PNDI-Tx, where x is the percentage of the single T. The acceptor PNDI-T10 is properly miscible with the low band gap donor polymer PTB7-Th, and the nanostructured blend promotes efficient exciton dissociation and charge transport. Solvent annealing (SA) enables higher hole and electron mobilities, and further suppresses the bimolecular recombination. As expected, the PTB7-Th:PNDI-T10 solar cells attain a high PCE of 7.6%, which is a 2-fold increase compared to that of PTB7-Th:N2200 solar cells. The FF of 0.71 reaches the highest value among all-PSCs to date. Our work demonstrates a rational design for fine-tuned crystallinity of polymer acceptors, and reveals the high potential of all-PSCs through structure and morphology engineering of semicrystalline polymer:polymer blends. PMID:27479751

  5. Evaluation of heart tissue viability under redox-magnetohydrodynamics conditions: toward fine-tuning flow in biological microfluidics applications.

    PubMed

    Cheah, Lih Tyng; Fritsch, Ingrid; Haswell, Stephen J; Greenman, John

    2012-07-01

    A microfluidic system containing a chamber for heart tissue biopsies, perfused with Krebs-Henseleit buffer containing glucose and antibiotic (KHGB) using peristaltic pumps and continuously stimulated, was used to evaluate tissue viability under redox-magnetohydrodynamics (redox-MHD) conditions. Redox-MHD possesses unique capabilities to control fluid flow using ionic current from oxidation and reduction processes at electrodes in a magnetic field, making it attractive to fine-tune fluid flow around tissues for "tissue-on-a-chip" applications. The manuscript describes a parallel setup to study two tissue samples simultaneously, and 6-min static incubation with Triton X100. Tissue viability was subsequently determined by assaying perfusate for lactate dehydrogenase (LDH) activity, where LDH serves as an injury marker. Incubation with KHGB containing 5 mM hexaammineruthenium(III) (ruhex) redox species with and without a pair of NdFeB magnets (∼ 0.39 T, placed parallel to the chamber) exhibited no additional tissue insult. MHD fluid flow, viewed by tracking microbeads with microscopy, occurred only when the magnet was present and stimulating electrodes were activated. Pulsating MHD flow with a frequency similar to the stimulating waveform was superimposed over thermal convection (from a hotplate) for Triton-KHGB, but fluid speed was up to twice as fast for ruhex-Triton-KHGB. A large transient ionic current, achieved when switching on the stimulating electrodes, generates MHD perturbations visible over varying peristaltic flow. The well-controlled flow methodology of redox-MHD is applicable to any tissue type, being useful in various drug uptake and toxicity studies, and can be combined equally with on- or off-device analysis modalities. PMID:22271160

  6. Fine-Tuning of the Cpx Envelope Stress Response Is Required for Cell Wall Homeostasis in Escherichia coli

    PubMed Central

    Delhaye, Antoine; Collet, Jean-François

    2016-01-01

    ABSTRACT The envelope of Gram-negative bacteria is an essential compartment that constitutes a protective and permeability barrier between the cell and its environment. The envelope also hosts the cell wall, a mesh-like structure made of peptidoglycan (PG) that determines cell shape and provides osmotic protection. Since the PG must grow and divide in a cell-cycle-synchronized manner, its synthesis and remodeling are tightly regulated. Here, we discovered that PG homeostasis is intimately linked to the levels of activation of the Cpx system, an envelope stress response system traditionally viewed as being involved in protein quality control in the envelope. We first show that Cpx is activated when PG integrity is challenged and that this activation provides protection to cells exposed to antibiotics inhibiting PG synthesis. By rerouting the outer membrane lipoprotein NlpE, a known Cpx activator, to a different envelope subcompartment, we managed to manipulate Cpx activation levels. We found that Cpx overactivation leads to aberrant cellular morphologies, to an increased sensitivity to β-lactams, and to dramatic division and growth defects, consistent with a loss of PG homeostasis. Remarkably, these phenotypes were largely abrogated by the deletion of ldtD, a Cpx-induced gene involved in noncanonical PG cross-linkage, suggesting that this transpeptidase is an important link between PG homeostasis and the Cpx system. Altogether our data show that fine-tuning of an envelope quality control system constitutes an important layer of regulation of the highly organized cell wall structure. PMID:26908573

  7. Fine-Tuning of the Fatty Acid Pathway by Synthetic Antisense RNA for Enhanced (2S)-Naringenin Production from l-Tyrosine in Escherichia coli

    PubMed Central

    Wu, Junjun; Yu, Oliver; Du, Guocheng

    2014-01-01

    Malonyl coenzyme A (malonyl-CoA) is an important precursor for the synthesis of natural products, such as polyketides and flavonoids. The majority of this cofactor often is consumed for producing fatty acids and phospholipids, leaving only a small amount of cellular malonyl-CoA available for producing the target compound. The tuning of malonyl-CoA into heterologous pathways yields significant phenotypic effects, such as growth retardation and even cell death. In this study, fine-tuning of the fatty acid pathway in Escherichia coli with antisense RNA (asRNA) to balance the demands on malonyl-CoA for target-product synthesis and cell health was proposed. To establish an efficient asRNA system, the relationship between sequence and function for asRNA was explored. It was demonstrated that the gene-silencing effect of asRNA could be tuned by directing asRNA to different positions in the 5′-UTR (untranslated region) of the target gene. Based on this principle, the activity of asRNA was quantitatively tailored to balance the need for malonyl-CoA in cell growth and the production of the main flavonoid precursor, (2S)-naringenin. Appropriate inhibitory efficiency of the anti-fabB/fabF asRNA improved the production titer by 431% (391 mg/liter). Therefore, the strategy presented in this study provided a useful tool for the fine-tuning of endogenous gene expression in bacteria. PMID:25239896

  8. Improving putrescine production by Corynebacterium glutamicum by fine-tuning ornithine transcarbamoylase activity using a plasmid addiction system.

    PubMed

    Schneider, Jens; Eberhardt, Dorit; Wendisch, Volker F

    2012-07-01

    Corynebacterium glutamicum shows a great potential for the production of the polyamide monomer putrescine (1,4-diaminobutane). Previously, we constructed the putrescine-producing strain PUT1 by deletion of argF, the gene for ornithine transcarbamoylase (OTC), and argR, encoding the L-arginine repressor, combined with heterologous expression of the Escherichia coli gene for L-ornithine decarboxylase SpeC. As a consequence of argF deletion, this strain requires supplementation of L-arginine and shows growth-decoupled putrescine production. To avoid costly supplementation with L-arginine and the strong feedback inhibition of the key enzyme N-acetylglutamate kinase (ArgB) by L-arginine, a plasmid addiction system for low-level argF expression was developed. By fine-tuning argF expression through modifications of the promoter, the translational start codon and/or the ribosome binding site, high productivity and titer could be obtained. OTC activity varied almost thousandfold between 960 and 1 mU mg⁻¹ resulting in putrescine yields on glucose from less than 0.001 up to 0.26 g g⁻¹, the highest yield in bacteria reported to date. The most promising strain, designated PUT21, was characterized comprehensively. PUT21 strain grew with a rate of 0.19 h⁻¹ in mineral salt medium without the need for L-arginine supplementation and produced putrescine with a yield of 0.16 g g⁻¹ glucose at a volumetric productivity of 0.57 g L⁻¹ h⁻¹ and a specific productivity of 0.042 g g⁻¹ h⁻¹. The carbon balance suggested that no major unidentified by-product was produced. Compared to the first-generation strain PUT1, the putrescine yield observed with PUT21 was increased by 60%. In fed-batch cultivation with C. glutamicum PUT21, a putrescine titer of 19 g L⁻¹ at a volumetric productivity of 0.55 g L⁻¹ h⁻¹ and a yield of 0.16 g g⁻¹ glucose could be achieved. Moreover, while plasmid segregation of the initial strain required antibiotic selection

  9. Vapor-melt Ratio in Laser Fine Cutting of Slot Arrays

    SciTech Connect

    Wang Xuyue; Meng Qingxuan; Kang Renke; Xu Wenji; Guo Dongming; Wang Lianji

    2011-05-04

    In order to improve cut quality for slot arrays, a new method of laser fine cutting under the consideration of the ratio of vapor to melt is presented. Laser cutting of 6063 aluminum alloy sheet, 0.5 mm in thickness, was carried out on a JK701H Nd:YAG pulse laser cutting system. The effects of vapor-melt ratio on kerf width, surface roughness and recast layer were studied which relate cutting qualities. Observation on the cut samples with different vapor-melt ratios (0.687, 1.574, 3.601 varied with laser power increasing, and 1.535, 3.601, 7.661 with decreasing of beam cutting speed) shows that high vapor-melt ratio improves laser cut quality clearly. Kerf width 0.2 mm of smooth area on kerf top area and thickness 2.03 {mu}m of recast layer are obtained. No dross was found on the kerf bottom and the percentage of the smooth area is up to 40% out of whole kerf side. The research on vapor-melt ratio provides a deeper understanding of laser cutting and improves laser cut quality effectively.

  10. Capability for Fine Tuning of the Refractive Index Sensing Properties of Long-Period Gratings by Atomic Layer Deposited Al2O3 Overlays

    PubMed Central

    Śmietana, Mateusz; Myśliwiec, Marcin; Mikulic, Predrag; Witkowski, Bartłomiej S.; Bock, Wojtek J.

    2013-01-01

    This work presents an application of thin aluminum oxide (Al2O3) films obtained using atomic layer deposition (ALD) for fine tuning the spectral response and refractive-index (RI) sensitivity of long-period gratings (LPGs) induced in optical fibers. The technique allows for an efficient and well controlled deposition at monolayer level (resolution ∼ 0.12 nm) of excellent quality nano-films as required for optical sensors. The effect of Al2O3 deposition on the spectral properties of the LPGs is demonstrated experimentally and numerically. We correlated both the increase in Al2O3 thickness and changes in optical properties of the film with the shift of the LPG resonance wavelength and proved that similar films are deposited on fibers and oxidized silicon reference samples in the same process run. Since the thin overlay effectively changes the distribution of the cladding modes and thus also tunes the device's RI sensitivity, the tuning can be simply realized by varying number of cycles, which is proportional to thickness of the high-refractive-index (n > 1.6 in infrared spectral range) Al2O3 film. The advantage of this approach is the precision in determining the film properties resulting in RI sensitivity of the LPGs. To the best of our knowledge, this is the first time that an ultra-precise method for overlay deposition has been applied on LPGs for RI tuning purposes and the results have been compared with numerical simulations based on LP mode approximation.

  11. Tuning of structural, optical, and magnetic properties of ultrathin and thin ZnO nanowire arrays for nano device applications

    NASA Astrophysics Data System (ADS)

    Shrama, Satinder K.; Saurakhiya, Neelam; Barthwal, Sumit; Kumar, Rudra; Sharma, Ashutosh

    2014-03-01

    One-dimensional (1-D) ultrathin (15 nm) and thin (100 nm) aligned 1-D (0001) and ([InlineEquation not available: see fulltext.]) oriented zinc oxide (ZnO) nanowire (NW) arrays were fabricated on copper substrates by one-step electrochemical deposition inside the pores of polycarbonate membranes. The aspect ratio dependence of the compressive stress because of the lattice mismatch between NW array/substrate interface and crystallite size variations is investigated. X-ray diffraction results show that the polycrystalline ZnO NWs have a wurtzite structure with a = 3.24 Å, c = 5.20 Å, and [002] elongation. HRTEM and SAED pattern confirmed the polycrystalline nature of ultrathin ZnO NWs and lattice spacing of 0.58 nm. The crystallite size and compressive stress in as-grown 15- and 100-nm wires are 12.8 nm and 0.2248 GPa and 22.8 nm and 0.1359 GPa, which changed to 16.1 nm and 1.0307 GPa and 47.5 nm and 1.1677 GPa after annealing at 873 K in ultrahigh vacuum (UHV), respectively. Micro-Raman spectroscopy showed that the increase in E2 (high) phonon frequency corresponds to much higher compressive stresses in ultrathin NW arrays. The minimum-maximum magnetization magnitude for the as-grown ultrathin and thin NW arrays are approximately 8.45 × 10-3 to 8.10 × 10-3 emu/g and approximately 2.22 × 10-7 to 2.190 × 10-7 emu/g, respectively. The magnetization in 15-nm NW arrays is about 4 orders of magnitude higher than that in the 100 nm arrays but can be reduced greatly by the UHV annealing. The origin of ultrathin and thin NW array ferromagnetism may be the exchange interactions between localized electron spin moments resulting from oxygen vacancies at the surfaces of ZnO NWs. The n-type conductivity of 15-nm NW array is higher by about a factor of 2 compared to that of the 100-nm ZnO NWs, and both can be greatly enhanced by UHV annealing. The ability to tune the stresses and the structural and relative occupancies of ZnO NWs in a wide range by annealing has important

  12. Experimental Profiling of a Non-truncated Focused Gaussian Beam and Fine-tuning of the Quadratic Phase in the Fresnel Gaussian Shape Invariant

    SciTech Connect

    S., Juan Manuel Franco; Cywiak, Moises; Cywiak, David; Mourad, Idir

    2015-06-24

    A homodyne profiler is used for recording the intensity distribution of focused non-truncated Gaussian beams. The spatial distributions are obtained at planes in the vicinity of the back-focal plane of a focusing lens placed at different distances from a He–Ne laser beam with a Gaussian intensity profile. Comparisons of the experimental data with those obtained from the analytical equations for an ideal focusing lens allow us to propose formulae to fine-tune the quadratic term in the Fresnel Gaussian shape invariant at each interface of the propagated field. Furthermore, we give analytical expressions to calculate adequately the propagation of the field through an optical system.

  13. Detection of Regional Infrasound Signals Using Array Data - Testing, Tuning, and Physical Interpretation

    NASA Astrophysics Data System (ADS)

    Park, J.; Stump, B. W.; Hayward, C.; Arrowsmith, S.; Che, I. Y.; Drob, D. P.

    2015-12-01

    In order to understand the impact environmental conditions have on infrasound detection, an automated detector that accounts for both correlated and uncorrelated noise is run on data from a number of infrasonic arrays, all in a regional context. Data from six seismo-acoustic arrays in South Korea (BRDAR, CHNAR, KMPAR, KSGAR, TJIAR, and YPDAR), which are cooperatively operated by Korea Institute of Geoscience and Mineral Resources (KIGAM) and Southern Methodist University (SMU), were used. An adaptive F-detector (AFD) (Arrowsmith et al., 2009) is applied that utilizes the F-statistic (Blandford, 1974) with an adaptive procedure that assesses variations in coherent noise in order to reduce false alarms. The adaptive procedure is characterized by the time dependent C-value that is found to depend on the weather conditions and local site effects. Arrays located on islands or near the coast produce noise power densities that are higher, consistent with both higher wind speeds as well as ocean wave contributions that vary seasonally. These results suggest that optimal detection processing requires careful characterization of background noise level and its relationship to enviornmental measures at individual arrays. This study also documents significant seasonal variations in infrasound detections including daily time of occurrence, total number of detections, and phase velocity/azimuth estimates. These time-dependent effects in most part explained by atmospheric models across the Korean peninsula as described by Drob et al. (2003).

  14. Enhancement of magnetic domain topologies in Co/Pt thin films by fine tuning the magnetic field path throughout the hysteresis loop

    NASA Astrophysics Data System (ADS)

    Westover, Andrew S.; Chesnel, Karine; Hatch, Kelsey; Salter, Philip; Hellwig, Olav

    2016-02-01

    We have studied the influence of magnetic history on the topology of perpendicular magnetic domains in a thin ferromagnetic film made of [Co(8 Å)/Pt(7 Å)]50 multilayers. More specifically, we have followed the morphological changes in the domain pattern when applying a magnetic field perpendicular to the layer, throughout minor and major magnetization loops, and in the resulting remanent state. We carried out this study by using MFM microscopy with an in-situ magnetic field. We find that the morphology of the magnetic domain pattern is greatly influenced by the magnetic history of the material and that some features, such as the degree of bubbliness (i.e., the extent of bubble domain formation) and density of isolated domains can be enhanced by fine tuning the magnetic field path within the major hysteresis loop towards different remanent states. In particular, we see how hysteresis is correlated to irreversible changes in the domain morphology. More interestingly, we find that the magnetic domain morphology at remanence can be changed from an interconnected labyrinthine stripe state to a state of many separated bubble domains by fine tuning the magnitude of the field previously applied to the material. These results agree well with other findings, such as the magnetic reversal behavior and magnetic memory effects in Co/Pt multilayers, and provide opportunities for potential technological applications.

  15. Nonlinear absorption tuning by composition control in bimetallic plasmonic nanoprism arrays

    NASA Astrophysics Data System (ADS)

    Cesca, Tiziana; Michieli, Niccolò; Kalinic, Boris; Sánchez-Espinoza, Ana; Rattin, Marco; Russo, Valentina; Mattarello, Valentina; Scian, Carlo; Mazzoldi, Paolo; Mattei, Giovanni

    2015-07-01

    The nonlinear absorption properties of bidimensional arrays of Au-Ag bilayered nanoprisms have been investigated by z-scan measurements as a function of the bimetallic nanoprism composition. A tunable ps laser system was used to excite the ultrafast, electronic nonlinear response matching the laser wavelength with the quadrupolar surface plasmon resonances, in the visible range, of each nanoprism array. Due to the strong electromagnetic field confinement effects at the nanoprism tips, demonstrated by finite element method simulations, these nanosystems proved to have enhanced nonlinear optical properties. Moreover, a tunable changeover from reverse saturable absorption (RSA) to saturable absorption (SA) can be obtained by properly controlling the bimetallic composition of the nanoprisms, without modifying the overall morphology of the nanosystems. This capability makes these nanosystems extremely interesting for the realization of solid-state nanophotonic devices with enhanced ultrafast nonlinear optical properties.The nonlinear absorption properties of bidimensional arrays of Au-Ag bilayered nanoprisms have been investigated by z-scan measurements as a function of the bimetallic nanoprism composition. A tunable ps laser system was used to excite the ultrafast, electronic nonlinear response matching the laser wavelength with the quadrupolar surface plasmon resonances, in the visible range, of each nanoprism array. Due to the strong electromagnetic field confinement effects at the nanoprism tips, demonstrated by finite element method simulations, these nanosystems proved to have enhanced nonlinear optical properties. Moreover, a tunable changeover from reverse saturable absorption (RSA) to saturable absorption (SA) can be obtained by properly controlling the bimetallic composition of the nanoprisms, without modifying the overall morphology of the nanosystems. This capability makes these nanosystems extremely interesting for the realization of solid

  16. Detection of regional infrasound signals using array data: Testing, tuning, and physical interpretation.

    PubMed

    Park, Junghyun; Stump, Brian W; Hayward, Chris; Arrowsmith, Stephen J; Che, Il-Young; Drob, Douglas P

    2016-07-01

    This work quantifies the physical characteristics of infrasound signal and noise, assesses their temporal variations, and determines the degree to which these effects can be predicted by time-varying atmospheric models to estimate array and network performance. An automated detector that accounts for both correlated and uncorrelated noise is applied to infrasound data from three seismo-acoustic arrays in South Korea (BRDAR, CHNAR, and KSGAR), cooperatively operated by Korea Institute of Geoscience and Mineral Resources (KIGAM) and Southern Methodist University (SMU). Arrays located on an island and near the coast have higher noise power, consistent with both higher wind speeds and seasonably variable ocean wave contributions. On the basis of the adaptive F-detector quantification of time variable environmental effects, the time-dependent scaling variable is shown to be dependent on both weather conditions and local site effects. Significant seasonal variations in infrasound detections including daily time of occurrence, detection numbers, and phase velocity/azimuth estimates are documented. These time-dependent effects are strongly correlated with atmospheric winds and temperatures and are predicted by available atmospheric specifications. This suggests that commonly available atmospheric specifications can be used to predict both station and network detection performance, and an appropriate forward model improves location capabilities as a function of time. PMID:27475150

  17. Tuning of structural, optical, and magnetic properties of ultrathin and thin ZnO nanowire arrays for nano device applications

    PubMed Central

    2014-01-01

    One-dimensional (1-D) ultrathin (15 nm) and thin (100 nm) aligned 1-D (0001) and (0001¯) oriented zinc oxide (ZnO) nanowire (NW) arrays were fabricated on copper substrates by one-step electrochemical deposition inside the pores of polycarbonate membranes. The aspect ratio dependence of the compressive stress because of the lattice mismatch between NW array/substrate interface and crystallite size variations is investigated. X-ray diffraction results show that the polycrystalline ZnO NWs have a wurtzite structure with a = 3.24 Å, c = 5.20 Å, and [002] elongation. HRTEM and SAED pattern confirmed the polycrystalline nature of ultrathin ZnO NWs and lattice spacing of 0.58 nm. The crystallite size and compressive stress in as-grown 15- and 100-nm wires are 12.8 nm and 0.2248 GPa and 22.8 nm and 0.1359 GPa, which changed to 16.1 nm and 1.0307 GPa and 47.5 nm and 1.1677 GPa after annealing at 873 K in ultrahigh vacuum (UHV), respectively. Micro-Raman spectroscopy showed that the increase in E2 (high) phonon frequency corresponds to much higher compressive stresses in ultrathin NW arrays. The minimum-maximum magnetization magnitude for the as-grown ultrathin and thin NW arrays are approximately 8.45 × 10−3 to 8.10 × 10−3 emu/g and approximately 2.22 × 10−7 to 2.190 × 10−7 emu/g, respectively. The magnetization in 15-nm NW arrays is about 4 orders of magnitude higher than that in the 100 nm arrays but can be reduced greatly by the UHV annealing. The origin of ultrathin and thin NW array ferromagnetism may be the exchange interactions between localized electron spin moments resulting from oxygen vacancies at the surfaces of ZnO NWs. The n-type conductivity of 15-nm NW array is higher by about a factor of 2 compared to that of the 100-nm ZnO NWs, and both can be greatly enhanced by UHV annealing. The ability to tune the stresses and the structural and relative occupancies of ZnO NWs in a wide range by annealing has

  18. 4 T Actively detuneable double-tuned 1H/31P head volume coil and four-channel 31P phased array for human brain spectroscopy.

    PubMed

    Avdievich, N I; Hetherington, H P

    2007-06-01

    Typically 31P in vivo magnetic resonance spectroscopic studies are limited by SNR considerations. Although phased arrays can improve the SNR; to date 31P phased arrays for high-field systems have not been combined with 31P volume transmit coils. Additionally, to provide anatomical reference for the 31P studies, without removal of the coil or patient from the magnet, double-tuning (31P/1H) of the volume coil is required. In this work we describe a series of methods for active detuning and decoupling enabling use of phased arrays with double-tuned volume coils. To demonstrate these principles we have built and characterized an actively detuneable 31P/1H TEM volume transmit/four-channel 31P phased array for 4 T magnetic resonance spectroscopic imaging (MRSI) of the human brain. The coil can be used either in volume-transmit/array-receive mode or in TEM transmit/receive mode with the array detuned. Threefold SNR improvement was obtained at the periphery of the brain using the phased array as compared to the volume coil. PMID:17379554

  19. Sensitivity Tuning through Additive Heterogeneous Plasmon Coupling between 3D Assembled Plasmonic Nanoparticle and Nanocup Arrays.

    PubMed

    Seo, Sujin; Zhou, Xiangfei; Liu, Gang Logan

    2016-07-01

    Plasmonic substrates have fixed sensitivity once the geometry of the structure is defined. In order to improve the sensitivity, significant research effort has been focused on designing new plasmonic structures, which involves high fabrication costs; however, a method is reported for improving sensitivity not by redesigning the structure but by simply assembling plasmonic nanoparticles (NPs) near the evanescent field of the underlying 3D plasmonic nanostructure. Here, a nanoscale Lycurgus cup array (nanoLCA) is employed as a base colorimetric plasmonic substrate and an assembly template. Compared to the nanoLCA, the NP assembled nanoLCA (NP-nanoLCA) exhibits much higher sensitivity for both bulk refractive index sensing and biotin-streptavidin binding detection. The limit of detection of the NP-nanoLCA is at least ten times smaller when detecting biotin-streptavidin conjugation. The numerical calculations confirm the importance of the additive plasmon coupling between the NPs and the nanoLCA for a denser and stronger electric field in the same 3D volumetric space. Tunable sensitivity is accomplished by controlling the number of NPs in each nanocup, or the number density of the hot spots. This simple yet scalable and cost-effective method of using additive heterogeneous plasmon coupling effects will benefit various chemical, medical, and environmental plasmon-based sensors. PMID:27206214

  20. Size-tuned Highly-ordered Magnetic Nanodot Arrays via ALD-Assisted Block Copolymer Nanolithography

    NASA Astrophysics Data System (ADS)

    Polisetty, Srinivas; Lin, Chun-Hao; Gladfelter, Wayne L.; Hillmyer, Marc H.; Leighton, Chris

    2014-03-01

    Block copolymer nanolithography of large-area well-ordered magnetic nanostructures is now possible via a variety of approaches and holds considerable appeal for fundamental science and for bit patterned recording media. Here, we demonstrate a non-lift-off damascene-type approach combined with low temperature atomic layer deposition (ALD) of a conformal ZnO layer to provide size-controlled magnetic nanodots. Perpendicularly-aligned nonporous templates were achieved by solvent annealing polystyrene- b-polylactide (PS-PLA) films. Low temperature ALD was then used to conformally coat the template with a ZnO layer of variable thickness to systematically reduce the pore diameter. Our damascene-type non-lift-off process was then used to synthesize Ni80Fe20 dot arrays from such templates, achieving tunable dot diameters (6-30 nm) and controlled dot height (by Ar milling time). Magnetic measurements were used as a probe of island volume, good agreement being obtained between simple calculations, imaging, and blocking temperature measurements. The results demonstrate a simple route to size control from a fixed polymer template, enabling detailed studies of separation-dependent inter-dot magnetic interactions for example. This work was supported primarily by the NSF through the University of Minnesota MRSEC under Award Number DMR-0819885.

  1. In situ tuning biexciton antibinding-binding transition and fine-structure splitting through hydrostatic pressure in single InGaAs quantum dots

    NASA Astrophysics Data System (ADS)

    Wu, X. F.; Wei, H.; Dou, X. M.; Ding, K.; Yu, Y.; Ni, H. Q.; Niu, Z. C.; Ji, Y.; Li, S. S.; Jiang, D. S.; Guo, G.-C.; He, L. X.; Sun, B. Q.

    2014-07-01

    Exciton and biexciton emission energies as well as excitonic fine-structure splitting (FSS) in single (In,Ga)As/GaAs quantum dots (QDs) have been continuously tuned using hydrostatic pressure up to 4.4 GPa. The blue shift of excitonic emission and the increase of FSS are 320 meV and 150\\ \\mu\\text{eV} , respectively, which are significantly greater than those that could be achieved by previously reported techniques. We successfully produce a biexciton antibinding-binding transition along with a detailed polarization-resolved emission spectra. It is shown that the biexciton binding energy linearly increases with increasing pressure and tends to be sublinear at high pressure. We have performed atomistic pseudopotential calculations on realistic QDs to understand the pressure-induced effects.

  2. In situ tuning biexciton antibinding-binding transition and fine structure splitting through hydrostatic pressure in single InGaAs quantum dots

    NASA Astrophysics Data System (ADS)

    Wei, Hai; Wu, Xuefei; Dou, Xiuming; Ding, Kun; Yu, Ying; Ni, Haiqiao; Niu, Zhichuan; Ji, Yang; Li, Shushen; Jiang, Desheng; Guo, Guang-Can; He, Lixin; Sun, Baoquan; Institute of Semiconductors, CAS, PR China Team; Key Laboratory of Quantum Information, University of Science; Technology of China, PR China Team

    2014-03-01

    We demonstrate that the exciton and biexciton emission energies as well as exciton fine structure splitting (FSS) in single (In,Ga)As/GaAs quantum dots (QDs) can be efficiently tuned using hydrostatic pressure in situ in an optical cryostat at up to 4.4 GPa. The maximum exciton emission energy shift is up to 380 meV, and the FSS is up to 150 μeV. We successfully produce a biexciton antibinding-binding transition in QDs, which is the key experimental condition that generates color- and polarization-indistinguishable photon pairs from the cascade of biexciton emissions and that generates entangled photons via a time-reordering scheme. We also perform the atomistic pseudopotential calculations on realistic (In,Ga)As/GaAs QDs to understand the physical mechanism underlying the hydrostatic pressure-induced effects.

  3. Applying high-resolution sequence stratigraphic tools to the Texas continental margin to fine-tune conventional sequence stratigraphic models and improve reservoir prediction

    SciTech Connect

    Anderson, J.A.; Banfield, L.A.; Eckles, B.J.

    1996-12-31

    A regional sequence stratigraphic study of the Texas continental margin resulted in an improved understanding of Pleistocene-Holocene eustatic sea level fluctuations and their influence on depositional environments associated with several distinct systems: the Colorado/Brazos system, the Texas interfluve region, and the Rio Grande system. The dataset consists of approximately 7500 kilometers of high-resolution seismic profiloes, 200 borehole descriptions, and 12 sediment cores. The study involved analysis of three independent variables to better constrain Pleistocene-Holocene sea level history: coastal onlap derived from high-resolution seismic profiles; oxygen isotope data determined from selected sediment cores; and paleoenvironmental data developed from high-resolution micropaleontologic analyses. Combined lithologic data and seismic facies analysis is used to map the distribution of major depositional systems on the shelf during one complete glacial eustatic cycle. Our study provided anopportunity to fine tune conventional stratigraphic models with regard to the distribution of potential reservoirs relative to regionally mappable stratigraphic surfaces.

  4. Applying high-resolution sequence stratigraphic tools to the Texas continental margin to fine-tune conventional sequence stratigraphic models and improve reservoir prediction

    SciTech Connect

    Anderson, J.A.; Banfield, L.A.; Eckles, B.J. )

    1996-01-01

    A regional sequence stratigraphic study of the Texas continental margin resulted in an improved understanding of Pleistocene-Holocene eustatic sea level fluctuations and their influence on depositional environments associated with several distinct systems: the Colorado/Brazos system, the Texas interfluve region, and the Rio Grande system. The dataset consists of approximately 7500 kilometers of high-resolution seismic profiloes, 200 borehole descriptions, and 12 sediment cores. The study involved analysis of three independent variables to better constrain Pleistocene-Holocene sea level history: coastal onlap derived from high-resolution seismic profiles; oxygen isotope data determined from selected sediment cores; and paleoenvironmental data developed from high-resolution micropaleontologic analyses. Combined lithologic data and seismic facies analysis is used to map the distribution of major depositional systems on the shelf during one complete glacial eustatic cycle. Our study provided anopportunity to fine tune conventional stratigraphic models with regard to the distribution of potential reservoirs relative to regionally mappable stratigraphic surfaces.

  5. Fine-Tuning of Polymeric Resins and Their Interfaces with Amorphous Calcium Phosphate. A Strategy for Designing Effective Remineralizing Dental Composites

    PubMed Central

    Antonucci, Joseph M.; Skrtic, Drago

    2011-01-01

    For over a decade our group has been designing, preparing and evaluating bioactive, remineralizing composites based on amorphous calcium phosphate (ACP) fillers embedded in polymerized methacrylate resin matrices. In these studies a major focus has been on exploring structure-property relationships of the matrix phase of these composites on their anti-cariogenic potential. The main challenges were to gain a better understanding of polymer matrix/filler interfacial properties through controlling the surface properties of the fillers or through fine-tuning of the resin matrix. In this work, we describe the effect of chemical structure and composition of the resin matrices on some of the critical physicochemical properties of the copolymers and their ACP composites. Such structure-property studies are essential in formulating clinically effective products, and this knowledge base is likely to have strong impact on the future design of therapeutic materials, appropriate for mineral restoration in defective tooth structures. PMID:21283507

  6. Consistency of LEP event excesses with an h{yields}aa decay scenario and low-fine-tuning next-to-minimal supersymmetric standard models

    SciTech Connect

    Dermisek, Radovan; Gunion, John F.

    2006-06-01

    We examine the LEP limits for the Zh{yields}Z+b's final state and find that the excess of observed events for m{sub h}{approx}100 GeV correlates well with there being an m{sub h}{approx}100 GeV Higgs boson with SM-like ZZh coupling that decays partly via h{yields}bb+{tau}{sup +}{tau}{sup -} [with B(h{yields}bb){approx}0.08] but dominantly via h{yields}aa [with B(h{yields}aa){approx}0.9], where m{sub a}<2m{sub b} so that a{yields}{tau}{sup +}{tau}{sup -} (or light quarks and gluons) decays are dominant. This type of scenario is precisely that predicted in the Next-to-Minimal Supersymmetric Model for parameter choices yielding the lowest possible fine-tuning.

  7. Fine Tuning of Nanocrystal and Pore Sizes of TiO2 Submicrospheres toward High Performance Dye-Sensitized Solar Cells.

    PubMed

    Li, Zhao-Qian; Ding, Yong; Mo, Li-E; Hu, Lin-Hua; Wu, Ji-Huai; Dai, Song-Yuan

    2015-10-14

    In general, the properties and performance of mesoporous TiO2 are greatly dependent on its crystal size, crystallinity, porosity, surface area, and morphology; in this regard, design and fine-tuning the crystal and pore sizes of the TiO2 submicrospheres and investigating the effect of these factors on the properties and photoelectric performance of dye-sensitized solar cells (DSSCs) is essential. In this work, uniform TiO2 submicrospheres were synthesized by a two-step procedure containing hydrolysis and solvothermal process. The crystal and pore sizes of the TiO2 submicrospheres were fine-tuned and controlled in a narrow range by adjusting the quantity of NH4OH during the solvothermal process. The effect of crystal and pore size of TiO2 submicrosphere on the performance of the DSSCs and their properties including dye-loading capacity, light scattering effect, power conversion efficiency (PCE), incident photon-to-electron conversion efficiencies (IPCEs), and electron recombination were compared and analyzed. The results show that increasing pore size plays a more significant role in improving the dye-loading capacity and PCE than increasing surface area, and an overall PCE value of 8.62% was obtained for the device with a 7.0 μm film thickness based on the TiO2 submicrospheres treated with 0.6 mL of NH4OH. Finally, the best TiO2 submicrosphere based photoanode film was optimized by TiCl4 treatment, and increasing film thickness and a remarkable PCE up to 11.11% were achieved. PMID:26393366

  8. Maximizing T2-exchange in Dy3+DOTA-(amide)X chelates: Fine-tuning the water molecule exchange rate for enhanced T2 contrast in MRI

    PubMed Central

    Soesbe, Todd C.; Ratnakar, S. James; Milne, Mark; Zhang, Shanrong; Do, Quyen N.; Kovacs, Zoltan; Sherry, A. Dean

    2014-01-01

    Purpose The water molecule exchange rates in a series of DyDOTA-(amide)X chelates were fine-tuned to maximize the effects of T2-exchange line broadening and improve T2 contrast. Methods Four DyDOTA-(amide)X chelates having a variable number of glycinate side-arms were prepared and characterized as T2-exchange agents. The non-exchanging DyTETA chelate was also used to measure the bulk water T2 reduction due solely to T2*. The total transverse relaxivity (r2tot) at 22, 37, and 52 °C for each chelate was measured in vitro at 9.4 T (400 MHz) by fitting plots of total T2−1 versus concentration. The water molecule exchange rates for each complex were measured by fitting 17O line-width versus temperature data taken at 9.4 T (54.3 MHz). Results The measured transverse relaxivities due to water molecule exchange (r2ex) and bound water lifetimes (τM) were in excellent agreement with Swift-Connick theory, with DyDOTA-(gly)3 giving the largest r2ex = 11.8 s−1 mM−1 at 37 °C. Conclusion By fine-tuning the water molecule exchange rate at 37 °C, the transverse relaxivity has been increased by 2 to 30 times compared to previously studied Dy3+-based chelates. Polymerization or dendrimerization of the optimal chelate could yield a highly sensitive, molecule-sized T2 contrast agent for improved molecular imaging applications. PMID:24390729

  9. Fine tuning of emission property of white light-emitting diodes by quantum-dot-coating on YAG:Ce nanophosphors

    NASA Astrophysics Data System (ADS)

    Kong, Dal Sung; Kim, Min Jeong; Song, Hee Jo; Cho, In Sun; Jeong, Sohee; Shin, Hyunjung; Lee, Sangwook; Jung, Hyun Suk

    2016-08-01

    We report fine tuning of emission color of Ce-doped yttrium aluminum garnet (Y3Al5O12:Ce3+, YAG:Ce) nanophosphor-based white light-emitting diodes (WLED), by coating CdSe/CdS/ZnS quantum dots (QDs) onto the surface of the YAG:Ce nanoparticles via surface functionalization of both the QDs and the YAG:Ce. Mixture of bromo-functionalized QDs and amino-functionalized YAG:Ce nanoparticles results in conformal coating of the QDs onto the YAG:Ce nanoparticles (QD@YAG:Ce). By varying the QD to YAG:Ce weight ratios, the luminescence spectra of the QD@YAG:Ce are tuned. A high-quality warm-white-light emission is achieved by appropriate combination of the yellow and red emissions from the QD@YAG:Ce, and the blue emission from InGaN LED chip. However, without surface functionalization, irregular mixtures of YAG:Ce and QDs are formed, which consequently make it hard to control the emission spectra. This study demonstrates a promising way to prepare uniformly QD-coated nanophosphors and an approach to control the emission spectra the nanophosphors.

  10. Self-powered ultraviolet photodetectors based on selectively grown ZnO nanowire arrays with thermal tuning performance.

    PubMed

    Bai, Zhiming; Chen, Xiang; Yan, Xiaoqin; Zheng, Xin; Kang, Zhuo; Zhang, Yue

    2014-05-28

    A self-powered Schottky-type ultraviolet photodetector with Al-Pt interdigitated electrodes has been fabricated based on selectively grown ZnO nanowire arrays. At zero bias, the fabricated photodetector exhibited high sensitivity and excellent selectivity to UV light illumination with a fast response time of 81 ms. By tuning the Schottky barrier height through the thermally induced variation of the interface chemisorbed oxygen, an ultrahigh sensitivity of 3.1 × 10(4) was achieved at 340 K without an external power source, which was 82% higher than that obtained at room temperature. According to the thermionic emission-diffusion theory and the solar cell theory, the changes in the photocurrent of the photodetector at zero bias with various system temperatures were calculated, which agreed well with the experimental data. This work demonstrates a promising approach to modulating the performance of a self-powered photodetector by heating and provides theoretical support for studying the thermal effect on the future photoelectric device. PMID:24728006

  11. Design of Far-Red Sensitizing Squaraine Dyes Aiming Towards the Fine Tuning of Dye Molecular Structure.

    PubMed

    Morimoto, Takuya; Fujikawa, Naotaka; Ogomi, Yuhei; Pandey, Shyam S; Ma, Tingli; Hayase, Shuzi

    2016-04-01

    Model squaraine dyes having sharp and narrow absorptions mainly in the far-red wavelength region has been logically designed, synthesized and used for their application as sensitizer in the dyesensitized solar cells (DSSC). In order to have fine control on energetics, dyes having same mother core and alkyl chain length varying only in molecular symmetry and position of substituent were designed. It has been found that even keeping all other structural factor constant, only positional variation of substituent leads to not only in the variation of energetics by 0.1 eV but affects the photovoltaic characteristics also. Optimum concentration of dye de-aggregating agent was found to be 100 times with respect to the sensitizing dye concentration. Amongst dyes utilized in this work best performance was obtained for unsymmetrical dye SQ-40 giving a photoconversion efficiency of 4.01% under simulated solar irradiation at global AM 1.5. PMID:27451618

  12. Fine tuning of copper(II)-chlorophyll interactions in organic media. Metalation versus oxidation of the macrocycle.

    PubMed

    Orzeł, Łukasz; Szmyd, Bartłomiej; Rutkowska-Żbik, Dorota; Fiedor, Leszek; van Eldik, Rudi; Stochel, Grażyna

    2015-04-01

    The nature of chlorophyll interactions with copper(II) ions varies considerably in organic solvents, depending on the dominant coordinative form. Besides formation of the metallo tetrapyrrolic complex, Cu(II) ions can cause oxidation of the pigment, reversible or irreversible, which can lead to the destruction of the macrocyclic structure. All these reaction types can be distinguished within a quite narrow range of reaction conditions. The ability to form new metallo derivatives in either metalation or transmetalation reactions is obviously limited by the concentration of the potential oxidant, but can be secured below this level via suitable composition of the reaction system. The decisive factor in the selection of a specific reaction pathway is the presence of a potential ligand that can affect the reactivity of Cu(II) for example by shifting its redox potential. Spectroscopic and electrochemical studies were performed in order to determine the predominant species of Cu(II) in methanol, nitromethane and acetonitrile in the presence of chloride and acetate ions, as well as to assign their appropriate oxidizing ability. This allowed us to estimate the boundary conditions for the electron transfer processes in chlorophyll-Cu(II) systems. Chlorophyll and its free base can undergo both types of electron transfer processes, however, they reveal different susceptibilities that make this class of ligands quite versatile markers in tuning the reactivity of metal ions in solutions. PMID:25720308

  13. Charge Sharing and Charge Loss in a Cadmium-Zinc-Telluride Fine-Pixel Detector Array

    NASA Technical Reports Server (NTRS)

    Gaskin, J. A.; Sharma, D. P.; Ramsey, B. D.; Six, N. Frank (Technical Monitor)

    2002-01-01

    Because of its high atomic number, room temperature operation, low noise, and high spatial resolution a Cadmium-Zinc-Telluride (CZT) multi-pixel detector is ideal for hard x-ray astrophysical observation. As part of on-going research at MSFC (Marshall Space Flight Center) to develop multi-pixel CdZnTe detectors for this purpose, we have measured charge sharing and charge loss for a 4x4 (750micron pitch), lmm thick pixel array and modeled these results using a Monte-Carlo simulation. This model was then used to predict the amount of charge sharing for a much finer pixel array (with a 300micron pitch). Future work will enable us to compare the simulated results for the finer array to measured values.

  14. Fine mapping of copy number variations on two cattle genome assemblies using high density SNP array

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Btau_4.0 and UMD3.1 are two distinct cattle reference genome assemblies. In our previous study using the low density BovineSNP50 array, we reported a copy number variation (CNV) analysis on Btau_4.0 with 521 animals of 21 cattle breeds, yielding 682 CNV regions with a total length of 139.8 megabases...

  15. The fine-tuning of thermosensitive and degradable polymer micelles for enhancing intracellular uptake and drug release in tumors.

    PubMed

    Li, Wei; Li, Jinfeng; Gao, Jie; Li, Bohua; Xia, Yu; Meng, Yanchun; Yu, Yongsheng; Chen, Huaiwen; Dai, Jianxin; Wang, Hao; Guo, Yajun

    2011-05-01

    Focusing on high temperature and low pH of tumor tissue, we prepared temperature and pH responsive poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide-b-lacitde) (PID(118)-b-PLA(59)) and poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide-b-ε-caprolactone) (PID(118)-b-PCL(60)) diblock copolymers with symmetric hydrophobic blocks by the reversible addition-fragmentation chain transfer (RAFT). The corresponding dual functional polymeric micelles were fabricated by dialysis methods. Their well-defined core-shell structure was characterized by (1)H NMR in D(2)O and further confirmed by TEM. Their structural and physical chemistry properties such as diameters (D), core corona dimension (R(core), R(shell)), distribution (PDI), M(w), aggregation number (N(agg)), second virial coefficient (A(2)), critical micellization concentration (CMC) and z-potential were firstly systemically investigated by dynamic and static laser light scattering. The volume phase transition temperature (VPTT) was around 40 °C above which the intracellular uptake of adriamycin (ADR) was significantly enhanced. Both flow cytometry and fluorescent microscopy showed that the ADR transported by these micelles was about 4 times higher than that by the commercial ADR formulation Taxotere®. In vitro cytotoxicity assay against N-87 cancer cell and confocal laser scanning microscopy (CLSM) also confirmed such promoting efficiency. In addition, it was interesting to find that cell surviving bounced back as T = 42 °C due to the inter-micellar aggregation. The well clarified mechanism strongly support that our finely tailored dual functional core-shell micelles are potent in enhancing cellular uptake and drug release. PMID:21377724

  16. Molecular assembly of highly symmetric molecules under a hydrogen bond framework controlled by alkyl building blocks: a simple approach to fine-tune nanoscale structures.

    PubMed

    Tanphibal, Pimsai; Tashiro, Kohji; Chirachanchai, Suwabun

    2016-01-14

    To date, molecular assemblies under the contribution of hydrogen bond in combination with weak interactions and their consequent morphologies have been variously reported; however, how the systematic variation of the structure can fine-tune the morphologies has not yet been answered. The present work finds an answer through highly symmetric molecules, i.e. diamine-based benzoxazine dimers. This type of molecule develops unique molecular assemblies with their networks formed by hydrogen bonds at the terminal, while, at the same time, their hydrogen bonded frameworks are further controlled by the hydrophobic segment at the center of the molecule. When this happens, slight differences in hydrophobic alkyl chain lengths (, , and ) bring a significant change to the molecular assemblies, thus resulting in tunable morphologies, i.e. spheres, needles and dendrites. The superimposition between the crystal lattice obtained from X-ray single crystal analysis and the electron diffraction pattern obtained from transmission electron microscopy allows us to identify the molecular alignment from single molecules to self-assembly until the morphologies developed. The present work, for the first time, shows the case of symmetric molecules, where the hydrophobic building block controls the hydrogen bond patterns, leading to the variation of molecular assemblies with tunable morphologies. PMID:26482133

  17. Preserved fine-tuning of face perception and memory: evidence from the own-race bias in high- and low-performing older adults

    PubMed Central

    Komes, Jessica; Schweinberger, Stefan R.; Wiese, Holger

    2014-01-01

    Previous research suggests specific deficits in face perception and memory in older adults, which could reflect a dedifferentiation in the context of a general broadening of cognitive architecture with advanced age. Such dedifferentiation could manifest in a less specialized face processing system. A promising tool to investigate the fine-tuning of face processing in older age is the own-race bias (ORB), a phenomenon reflecting more accurate memory for own-relative to other-race faces, which is related to an expertise-based specialization of early perceptual stages. To investigate whether poor face memory in older age is accompanied by reduced expertise-based specialization of face processing, we assessed event-related brain potential correlates of the ORB in high- vs. low-performing older adults (mean age = 69 years; N = 24 per group). Intriguingly, both older groups demonstrated an equivalent pattern of a behavioral ORB, and a parallel increase in N170 for other-race faces, reflecting less efficient early perceptual processing for this face category. Group differences only emerged independent of face ethnicity: whereas low-performers exhibited a right-lateralized N170, high-performers showed a more bilateral response. This finding may suggest a compensatory mechanism counteracting age-related decline in face perception enabling more efficient encoding into memory in high performers. Overall, our results demonstrate that even a less efficient face processing system in older adults can exhibit preserved expertise-related specialization toward own-race faces. PMID:24772080

  18. Fine-Tuning of β-Substitution to Modulate the Lowest Triplet Excited States: A Bioinspired Approach to Design Phosphorescent Metalloporphyrinoids.

    PubMed

    Ke, Xian-Sheng; Zhao, Hongmei; Zou, Xiaoran; Ning, Yingying; Cheng, Xin; Su, Hongmei; Zhang, Jun-Long

    2015-08-26

    Learning nature's approach to modulate photophysical properties of NIR porphyrinoids by fine-tuning β-substituents including the number and position, in a manner similar to naturally occurring chlorophylls, has the potential to circumvent the disadvantages of traditional "extended π-conjugation" strategy such as stability, molecular size, solubility, and undesirable π-π stacking. Here we show that such subtle structural changes in Pt(II) or Pd(II) cis/trans-porphodilactones (termed by cis/trans-Pt/Pd) influence photophysical properties of the lowest triplet excited states including phosphorescence, Stokes shifts, and even photosensitization ability in triplet-triplet annihilation reactions with rubrene. Prominently, the overall upconversion capability (η, η = ε·Φ(UC)) of Pd or Pt trans-complex is 10(4) times higher than that of cis-analogue. Nanosecond time-resolved infrared (TR-IR) spectroscopy experiments showed larger frequency shift of ν(C═O) bands (ca. 10 cm(-1)) of cis-complexes than those of trans-complexes in the triplet excited states. These spectral features, combining with TD-DFT calculations, suggest the strong electronic coupling between the lactone moieties and the main porphyrin chromophores and thus the importance of precisely positioning β-substituents by mimicking chlorophylls, as an alternative to "extended π-conjugation", in designing NIR active porphyrinoids. PMID:26247480

  19. Fine-tuning of catalytic tin nanoparticles by the reverse micelle method for direct deposition of silicon nanowires by a plasma-enhanced chemical vapour technique.

    PubMed

    Poinern, Gérrard E J; Ng, Yan-Jing; Fawcett, Derek

    2010-12-15

    The reverse micelle method was used for the reduction of a tin (Sn) salt solution to produce metallic Sn nanoparticles ranging from 85 nm to 140 nm in diameter. The reverse micellar system used in this process was hexane-butanol-cetyl trimethylammonium bromide (CTAB). The diameters of the Sn nanoparticles were proportional to the concentration of the aqueous Sn salt solution. Thus, the size of the Sn nanoparticles can easily be controlled, enabling a simple, reproducible mechanism for the growth of silicon nanowires (SiNWs) using plasma-enhanced chemical vapour deposition (PECVD). Both the Sn nanoparticles and silicon nanowires were characterised using field-emission scanning electron microscopy (FE-SEM). Further characterisations of the SiNW's were made using transmission electron microscopy (TEM), atomic force microscopy (AFM) and Raman spectroscopy. In addition, dynamic light scattering (DLS) was used to investigate particle size distributions. This procedure demonstrates an economical route for manufacturing reproducible silicon nanowires using fine-tuned Sn nanoparticles for possible solar cell applications. PMID:20887996

  20. The Catalytic and Non-catalytic Functions of the Brahma Chromatin-Remodeling Protein Collaborate to Fine-Tune Circadian Transcription in Drosophila

    PubMed Central

    Kwok, Rosanna S.; Li, Ying H.; Lei, Anna J.; Edery, Isaac; Chiu, Joanna C.

    2015-01-01

    Daily rhythms in gene expression play a critical role in the progression of circadian clocks, and are under regulation by transcription factor binding, histone modifications, RNA polymerase II (RNAPII) recruitment and elongation, and post-transcriptional mechanisms. Although previous studies have shown that clock-controlled genes exhibit rhythmic chromatin modifications, less is known about the functions performed by chromatin remodelers in animal clockwork. Here we have identified the Brahma (Brm) complex as a regulator of the Drosophila clock. In Drosophila, CLOCK (CLK) is the master transcriptional activator driving cyclical gene expression by participating in an auto-inhibitory feedback loop that involves stimulating the expression of the main negative regulators, period (per) and timeless (tim). BRM functions catalytically to increase nucleosome density at the promoters of per and tim, creating an overall restrictive chromatin landscape to limit transcriptional output during the active phase of cycling gene expression. In addition, the non-catalytic function of BRM regulates the level and binding of CLK to target promoters and maintains transient RNAPII stalling at the per promoter, likely by recruiting repressive and pausing factors. By disentangling its catalytic versus non-catalytic functions at the promoters of CLK target genes, we uncovered a multi-leveled mechanism in which BRM fine-tunes circadian transcription. PMID:26132408

  1. Direct flow cytometry measurements reveal a fine-tuning of symbiotic cell dynamics according to the host developmental needs in aphid symbiosis

    PubMed Central

    Simonet, Pierre; Duport, Gabrielle; Gaget, Karen; Weiss-Gayet, Michèle; Colella, Stefano; Febvay, Gérard; Charles, Hubert; Viñuelas, José; Heddi, Abdelaziz; Calevro, Federica

    2016-01-01

    Endosymbiotic associations constitute a driving force in the ecological and evolutionary diversification of metazoan organisms. Little is known about whether and how symbiotic cells are coordinated according to host physiology. Here, we use the nutritional symbiosis between the insect pest, Acyrthosiphon pisum, and its obligate symbiont, Buchnera aphidicola, as a model system. We have developed a novel approach for unculturable bacteria, based on flow cytometry, and used this method to estimate the absolute numbers of symbionts at key stages of aphid life. The endosymbiont population increases exponentially throughout nymphal development, showing a growing rate which has never been characterized by indirect molecular techniques. Using histology and imaging techniques, we have shown that the endosymbiont-bearing cells (bacteriocytes) increase significantly in number and size during the nymphal development, and clustering in the insect abdomen. Once adulthood is reached and the laying period has begun, the dynamics of symbiont and host cells is reversed: the number of endosymbionts decreases progressively and the bacteriocyte structure degenerates during insect aging. In summary, these results show a coordination of the cellular dynamics between bacteriocytes and primary symbionts and reveal a fine-tuning of aphid symbiotic cells to the nutritional demand imposed by the host physiology throughout development. PMID:26822159

  2. Full phosphorescent white-light organic light-emitting diodes with improved color stability and efficiency by fine tuning primary emission contributions

    SciTech Connect

    Hua, Wang E-mail: wanghua001@tyut.edu.cn; Du, Xiaogang; Su, Wenming E-mail: wanghua001@tyut.edu.cn; Zhang, Dongyu; Lin, Wenjing

    2014-02-15

    In this paper, a novel type of white-light organic light emitting diode (OLED) with high color stability was reported, in which the yellow-light emission layer of (4,4{sup ′}-N,N{sup ′}-dicarbazole)biphenyl (CBP) : tris(2-phenylquinoline-C2,N{sup ′})iridium(III) (Ir(2-phq){sub 3}) was sandwiched by double blue-light emission layers of 1,1-bis-[(di-4-tolylamino)pheny1]cyclohexane (TAPC) : bis[4,6-(di-fluorophenyl)-pyridinato-N,C2{sup ′}]picolinate (FIrpic) and tris[3-(3-pyridyl)mesityl]borane (3TPYMB):FIrpic. And, it exhibited the maximum current efficiency of 33.1 cd/A, the turn-on voltage at about 3 V and the maximum luminance in excess of 20000 cd/m{sup 2}. More important, it realized very stable white-light emission, and its CIE(x, y) coordinates only shift from (0.34, 0.37) to (0.33, 0.37) as applied voltage increased from 5 V to 12 V. It is believed that the new scheme in emission layer of white-light OLED can fine tune the contribution of primary emission with applied voltage changed, resulting in high quality white-light OLED.

  3. Pore radius fine tuning of a silica matrix (MCM-41) based on the synthesis of alumina nanolayers with different thicknesses by atomic layer deposition

    SciTech Connect

    Zemtsova, Elena G. Arbenin, Andrei Yu.; Plotnikov, Alexander F.; Smirnov, Vladimir M.

    2015-03-15

    The authors investigated a new approach to modify the surface of the mesoporous silica matrix MCM-41. This approach is based on manipulating the chemical composition of the porous surface layer and also on fine tuning the pore radius by applying the atomic layer deposition (ALD) technique. The synthesis of alumina nanolayers was performed on the planar and the porous matrix (MCM-41) by the ALD technique using aluminum tri-sec-butoxide and water as precursors. The authors show that one cycle on silicon, using aluminum tri-sec-butoxide and water as precursors, results in a 1–1.2 Å increase in alumina nanolayer thickness. This is comparable to the increase in thickness per cycle for other precursors such as trimethylaluminum and aluminum chloride. The authors show that the synthesis of an Al{sub 2}O{sub 3} nanolayer on the pore surface of the mesoporous silica matrix MCM-41 by the ALD technique results in a regular change in the porous structure of the samples. The specific porosity (ml/g) of the MCM-41 was 0.95 and that of MCM-41 after 5 ALD cycles was 0.39. The pore diameter (nm) of MCM-41 was 3.3 and that of MCM-41 after 5 ALD cycles was 2.3.

  4. 3′-UTR engineering to improve soluble expression and fine-tuning of activity of cascade enzymes in Escherichia coli

    PubMed Central

    Song, Ji-Won; Woo, Ji-Min; Jung, Gyoo Yeol; Bornscheuer, Uwe T.; Park, Jin-Byung

    2016-01-01

    3′-Untranslated region (3′UTR) engineering was investigated to improve solubility of heterologous proteins (e.g., Baeyer-Villiger monooxygenases (BVMOs)) in Escherichia coli. Insertion of gene fragments containing putative RNase E recognition sites into the 3′UTR of the BVMO genes led to the reduction of mRNA levels in E. coli. Importantly, the amounts of soluble BVMOs were remarkably enhanced resulting in a proportional increase of in vivo catalytic activities. Notably, this increase in biocatalytic activity correlated to the number of putative RNase E endonucleolytic cleavage sites in the 3′UTR. For instance, the biotransformation activity of the BVMO BmoF1 (from Pseudomonas fluorescens DSM50106) in E. coli was linear to the number of RNase E cleavage sites in the 3′UTR. In summary, 3′UTR engineering can be used to improve the soluble expression of heterologous enzymes, thereby fine-tuning the enzyme activity in microbial cells. PMID:27406241

  5. Fine-Tuning of CD8(+) T Cell Mitochondrial Metabolism by the Respiratory Chain Repressor MCJ Dictates Protection to Influenza Virus.

    PubMed

    Champagne, Devin P; Hatle, Ketki M; Fortner, Karen A; D'Alessandro, Angelo; Thornton, Tina M; Yang, Rui; Torralba, Daniel; Tomás-Cortázar, Julen; Jun, Yong Woong; Ahn, Kyo Han; Hansen, Kirk C; Haynes, Laura; Anguita, Juan; Rincon, Mercedes

    2016-06-21

    Mitochondrial respiration is regulated in CD8(+) T cells during the transition from naive to effector and memory cells, but mechanisms controlling this process have not been defined. Here we show that MCJ (methylation-controlled J protein) acted as an endogenous break for mitochondrial respiration in CD8(+) T cells by interfering with the formation of electron transport chain respiratory supercomplexes. Metabolic profiling revealed enhanced mitochondrial metabolism in MCJ-deficient CD8(+) T cells. Increased oxidative phosphorylation and subcellular ATP accumulation caused by MCJ deficiency selectively increased the secretion, but not expression, of interferon-γ. MCJ also adapted effector CD8(+) T cell metabolism during the contraction phase. Consequently, memory CD8(+) T cells lacking MCJ provided superior protection against influenza virus infection. Thus, MCJ offers a mechanism for fine-tuning CD8(+) T cell mitochondrial metabolism as an alternative to modulating mitochondrial mass, an energetically expensive process. MCJ could be a therapeutic target to enhance CD8(+) T cell responses. PMID:27234056

  6. The cell-specific activity of the estrogen receptor α may be fine-tuned by phosphorylation-induced structural gymnastics

    PubMed Central

    Gburcik, Valentina; Picard, Didier

    2006-01-01

    The estrogen receptor α (ERα) regulates the transcription of target genes by recruiting coregulator proteins through several domains including the two activation functions AF1 and AF2. The contribution of the N-terminally located AF1 activity is particularly important in differentiated cells, and for ERα to integrate inputs from other signaling pathways. However, how the phosphorylation of key residues influences AF1 activity has long remained mysterious, in part because the naturally disordered AF1 domain has resisted a structural characterization. The recent discovery of two coregulators that are specific for a phosphorylated form of AF1 suggests that phosphorylation, possibly in conjunction with the subsequent binding of these coregulators, may enforce a stable structure. The binding of the "pioneer" coregulators might facilitate the subsequent recruitment of yet other coregulators. Different AF1 folds may be enabled by the combinatorial action of posttranslational modifications and coregulator binding thereby fine-tuning ERα activities in a cell- and promoter-specific fashion. PMID:16604168

  7. Direct flow cytometry measurements reveal a fine-tuning of symbiotic cell dynamics according to the host developmental needs in aphid symbiosis.

    PubMed

    Simonet, Pierre; Duport, Gabrielle; Gaget, Karen; Weiss-Gayet, Michèle; Colella, Stefano; Febvay, Gérard; Charles, Hubert; Viñuelas, José; Heddi, Abdelaziz; Calevro, Federica

    2016-01-01

    Endosymbiotic associations constitute a driving force in the ecological and evolutionary diversification of metazoan organisms. Little is known about whether and how symbiotic cells are coordinated according to host physiology. Here, we use the nutritional symbiosis between the insect pest, Acyrthosiphon pisum, and its obligate symbiont, Buchnera aphidicola, as a model system. We have developed a novel approach for unculturable bacteria, based on flow cytometry, and used this method to estimate the absolute numbers of symbionts at key stages of aphid life. The endosymbiont population increases exponentially throughout nymphal development, showing a growing rate which has never been characterized by indirect molecular techniques. Using histology and imaging techniques, we have shown that the endosymbiont-bearing cells (bacteriocytes) increase significantly in number and size during the nymphal development, and clustering in the insect abdomen. Once adulthood is reached and the laying period has begun, the dynamics of symbiont and host cells is reversed: the number of endosymbionts decreases progressively and the bacteriocyte structure degenerates during insect aging. In summary, these results show a coordination of the cellular dynamics between bacteriocytes and primary symbionts and reveal a fine-tuning of aphid symbiotic cells to the nutritional demand imposed by the host physiology throughout development. PMID:26822159

  8. The histone H2A deubiquitinase USP16 interacts with HERC2 and fine-tunes cellular response to DNA damage.

    PubMed

    Zhang, Zhuo; Yang, Huirong; Wang, Hengbin

    2014-11-21

    Histone ubiquitination at DNA double strand breaks facilitates the recruitment of downstream repair proteins; however, how the ubiquitination is dynamically regulated during repair and terminated after repair is not well understood. Here we report that the histone H2A deubiquitinase USP16 interacts with HERC2, fine-tunes the ubiquitin signal during repair, and importantly, is required for terminating the ubiquitination signal after repair. HERC2 interacts with the coiled-coil domain of USP16 through its C-terminal HECT domain. HERC2 knockdown affects the levels of ubiquitinated H2A through the action of USP16. In response to DNA damage, USP16 levels increase, and this increase is dependent on HERC2. Increased USP16 serves as a negative regulator for DNA damage-induced ubiquitin foci formation and affects downstream factor recruitment and DNA damage response. The functional significance of USP16 is further manifested in human Down syndrome patient cells, which contain three copies of USP16 genes and have altered cellular response to DNA damage. Finally, we demonstrated that USP16 could deubiquitinate both H2A Lys-119 and H2A Lys-15 ubiquitination in vitro. Therefore, this study identifies USP16 as a critical regulator of DNA damage response and H2A Lys-15 ubiquitination as a potential target of USP16. PMID:25305019

  9. Fine-tuning motor torque

    SciTech Connect

    O`Connor, L.

    1996-01-01

    Direct-torque control, a new method of regulating the output of ac induction motors, provides a swift response to input commands. A new variable-speed ac motor drive system that responds to torque input commands 10 times faster than current state-of-the-art drives has been developed by ABB Industrial Systems Inc. in New Berlin, Wis. The new control system, called the ACS 600, provides an alternative to drive systems that use sophisticated flux vector control or more routine pulse width modulation--the primary methods of regulating the output of ac induction motors. The ACS 600 is suitable for use in single motor applications that require a standard level of performance, such as conveyors, fans, and pumps. But it will likely be more valuable in applications that require the linking of multiple motors, such as textile production, and in applications that require tight control over torque, such as cranes, elevators, and centrifuges.

  10. Fine-Tuning Teacher Evaluation

    ERIC Educational Resources Information Center

    Marshall, Kim

    2012-01-01

    As many states and districts rethink teacher supervision and evaluation, the team at the Measures of Effective Teaching (MET) Project, funded by the Bill and Melinda Gates Foundation, has analyzed thousands of lesson videotapes and studied the shortcomings of current practices. The tentative conclusion: Teachers should be evaluated on three…

  11. Fine tuning brings noteworthy success.

    PubMed

    Baillie, Jonathan

    2009-11-01

    Over the past year the estates and facilities team at London's UCLH NHS Foundation Trust and Interserve Consulting have jointly analysed energy consumption at University College Hospital to identify saving opportunities and potential carbon footprint reduction measures. The project, under which measures proposed could see electrical energy demand cut by 25%, is just part of a wider drive to reduce carbon emissions and cut energy bills at one of London's largest hospitals. Jonathan Baillie reports. PMID:19998839

  12. Fine-tuning Philippine transactions

    SciTech Connect

    Vitale, R.

    1994-11-01

    Expanding the power generation and distribution capability of the Philippines remains a top priority of the Philippine government. It is therefore not surprising that a number of the most significant legislative initiatives approved by the Philippine legislature in the past few years have been designed to encourage these activities in particular. There are several recent, significant statutes that will affect both power and non-power projects undertaken in the Philippines.

  13. MicroRNA-15a fine-tunes the level of Delta-like 1 homolog (DLK1) in proliferating 3T3-L1 preadipocytes

    SciTech Connect

    Andersen, Ditte C.; Schneider, Mikael; Eskildsen, Tilde; Teisner, Borge; and others

    2010-06-10

    Delta like 1 homolog (Dlk1) exists in both transmembrane and soluble molecular forms, and is implicated in cellular growth and plays multiple roles in development, tissue regeneration, and cancer. Thus, DLK1 levels are critical for cell function, and abnormal DLK1 expression can be lethal; however, little is known about the underlying mechanisms. We here report that miR-15a modulates DLK1 levels in preadipocytes thus providing a mechanism for DLK1 regulation that further links it to cell cycle arrest and cancer since miR-15a is deregulated in these processes. In preadipocytes, miR-15a increases with cell density, and peaks at the same stage where membrane DLK1{sup M} and soluble DLK1{sup S} are found at maximum levels. Remarkably, miR-15a represses the amount of all Dlk1 variants at the mRNA level but also the level of DLK1{sup M} protein while it increases the amount of DLK1{sup S} supporting a direct repression of DLK1 and a parallel effect on the protease that cleaves off the DLK1 from the membrane. In agreement with previous studies, we found that miR-15a represses cell numbers, but additionally, we report that miR-15a also increases cell size. Conversely, anti-miR-15a treatment decreases cell size while increasing cell numbers, scenarios that were completely rescued by addition of purified DLK1{sup S}. Our data thus imply that miR-15a regulates cell size and proliferation by fine-tuning Dlk1 among others, and further emphasize miR-15a and DLK1 levels to play important roles in growth signaling networks.

  14. In response to partial plant shading, the lack of phytochrome A does not directly induce leaf senescence but alters the fine-tuning of chlorophyll biosynthesis

    PubMed Central

    Brouwer, Bastiaan; Gardeström, Per; Keech, Olivier

    2014-01-01

    Phytochrome is thought to control the induction of leaf senescence directly, however, the signalling and molecular mechanisms remain unclear. In the present study, an ecophysiological approach was used to establish a functional connection between phytochrome signalling and the physiological processes underlying the induction of leaf senescence in response to shade. With shade it is important to distinguish between complete and partial shading, during which either the whole or only a part of the plant is shaded, respectively. It is first shown here that, while PHYB is required to maintain chlorophyll content in a completely shaded plant, only PHYA is involved in maintaining the leaf chlorophyll content in response to partial plant shading. Second, it is shown that leaf yellowing associated with strong partial shading in phyA-mutant plants actually correlates to a decreased biosynthesis of chlorophyll rather than to an increase of its degradation. Third, it is shown that the physiological impact of this decreased biosynthesis of chlorophyll in strongly shaded phyA-mutant leaves is accompanied by a decreased capacity to adjust the Light Compensation Point. However, the increased leaf yellowing in phyA-mutant plants is not accompanied by an increase of senescence-specific molecular markers, which argues against a direct role of PHYA in inducing leaf senescence in response to partial shade. In conclusion, it is proposed that PHYA, but not PHYB, is essential for fine-tuning the chlorophyll biosynthetic pathway in response to partial shading. In turn, this mechanism allows the shaded leaf to adjust its photosynthetic machinery to very low irradiances, thus maintaining a positive carbon balance and repressing the induction of leaf senescence, which can occur under prolonged periods of shade. PMID:24604733

  15. Surface charge fine tuning of reversed-phase/weak anion-exchange type mixed-mode stationary phases for milder elution conditions.

    PubMed

    Zimmermann, Aleksandra; Horak, Jeannie; Sánchez-Muñoz, Orlando L; Lämmerhofer, Michael

    2015-08-28

    A series of new mixed-mode reversed-phase/weak anion-exchange (RP/WAX) phases have been synthesized by immobilization of N-undecenyl-3-α-aminotropane onto thiol-modified silica gel by thiol-ene click chemistry and subsequent introduction of acidic thiol-endcapping functionalities of different type and surface densities. Click chemistry allowed to adjust a controlled surface concentration of the RP/WAX ligand in such a way that a sufficient quantity of residual thiols remained unmodified which have been capped by thiol click with either 3-butenoic acid or allylsulfonic acid as co-ligands. In another embodiment, performic acid oxidation of N-undecenyl-3-α-aminotropane-derivatized thiol-modified silica gave a RP/WAX phase with high density of sulfonic acid end-capping groups. ζ-Potential determinations confirmed the fine-tuned pI of these mixed-mode stationary phases which was shifted from 9.5 to 8.2, 7.8, and 6.5 with 3-butenoic acid and allylsulfonic acid end-capping as well as performic acid oxidation. For acidic solutes, the co-ionic endcapping leads to strongly reduced retention times and clearly allowed elution of these analytes under lower ionic strength thus milder elution conditions. In spite of the acidic endcapping, the new mixed-mode phases maintained their hydrophobic and anion-exchange selectivity as well as their multimodal nature featuring RP and HILIC elution domains at acetonitrile percentages below and above 50%, respectively. Column classification by principal component analysis of an extended retention map in comparison to a set of polar commercial and in-house synthesized stationary phases confirmed complementarity of the new mixed-mode phases with respect to HILIC, polar RP, amino and commercial mixed-mode phases. PMID:26206629

  16. OsNAP connects abscisic acid and leaf senescence by fine-tuning abscisic acid biosynthesis and directly targeting senescence-associated genes in rice

    PubMed Central

    Liang, Chengzhen; Wang, Yiqin; Zhu, Yana; Tang, Jiuyou; Hu, Bin; Liu, Linchuan; Ou, Shujun; Wu, Hongkai; Sun, Xiaohong; Chu, Jinfang; Chu, Chengcai

    2014-01-01

    It has long been established that premature leaf senescence negatively impacts the yield stability of rice, but the underlying molecular mechanism driving this relationship remains largely unknown. Here, we identified a dominant premature leaf senescence mutant, prematurely senile 1 (ps1-D). PS1 encodes a plant-specific NAC (no apical meristem, Arabidopsis ATAF1/2, and cup-shaped cotyledon2) transcriptional activator, Oryza sativa NAC-like, activated by apetala3/pistillata (OsNAP). Overexpression of OsNAP significantly promoted senescence, whereas knockdown of OsNAP produced a marked delay of senescence, confirming the role of this gene in the development of rice senescence. OsNAP expression was tightly linked with the onset of leaf senescence in an age-dependent manner. Similarly, ChIP-PCR and yeast one-hybrid assays demonstrated that OsNAP positively regulates leaf senescence by directly targeting genes related to chlorophyll degradation and nutrient transport and other genes associated with senescence, suggesting that OsNAP is an ideal marker of senescence onset in rice. Further analysis determined that OsNAP is induced specifically by abscisic acid (ABA), whereas its expression is repressed in both aba1 and aba2, two ABA biosynthetic mutants. Moreover, ABA content is reduced significantly in ps1-D mutants, indicating a feedback repression of OsNAP on ABA biosynthesis. Our data suggest that OsNAP serves as an important link between ABA and leaf senescence. Additionally, reduced OsNAP expression leads to delayed leaf senescence and an extended grain-filling period, resulting in a 6.3% and 10.3% increase in the grain yield of two independent representative RNAi lines, respectively. Thus, fine-tuning OsNAP expression should be a useful strategy for improving rice yield in the future. PMID:24951508

  17. Could there be a fine-tuning role for brain-derived adipokines in the regulation of bodyweight and prevention of obesity?

    PubMed Central

    Brown, Russell E.

    2008-01-01

    Obesity is one of the most prevalent medical conditions, often associated with several negative stereotypes. Although it is true that weight gain occurs when food intake exceeds energy expenditure, it is important to note that even a 1% mismatch between the two can lead to a substantial weight gain after only a few years. Further, the body appears to balance energy metabolism via an endogenous lipostatic loop in which adipose stores send hormonal signals (e.g. adipokines such as leptin) to the hypothalamus in order to reduce appetite and increase energy expenditure. However, the brain is also a novel site of expression of many of these adipokine genes. This led to the hypothesis that hypothalamic-derived adipokines might also be involved in bodyweight regulation by exerting some effect on the control of appetite or hypothalamic function. When RNA interference (RNAi) was used to specifically silence adipokine gene expression in various in vitro models, this led to increases in cell death, modification of the expression of key signaling genes (i.e. suppressor of cytokine signaling-3; SOCS-3), and modulation of the activation of cellular energy sensors (i.e. adenosine monophosphate-activated protein kinase; AMPK). Subsequently, when RNAi was used to inhibit the expression of brain-derived leptin in adult rats this resulted in minor increases in weight gain in addition to modifying the expression of other adipokine genes (eg. resistin). In summary, although adipokines secreted by adipose tissue appear to the main regulator of lipostatic loop, this review shows that the fine tuning that is required to maintain a stable bodyweight by this system might be accomplished by hypothalamic-derived adipokines. Perturbations in this central adipokine system could lead to alterations in normal hypothalamic function which leads to unintended weight gain. PMID:19148319

  18. PERK regulated miR-424(322)-503 cluster fine-tunes activation of IRE1 and ATF6 during Unfolded Protein Response

    PubMed Central

    Gupta, Ananya; Hossain, Muhammad Mosaraf; Read, Danielle E.; Hetz, Claudio; Samali, Afshin; Gupta, Sanjeev

    2015-01-01

    The endoplasmic reticulum (ER) responds to changes in intracellular homeostasis through activation of the unfolded protein response (UPR). UPR can facilitate the restoration of cellular homeostasis, via the concerted activation of three ER stress sensors, namely IRE1, PERK and ATF6. Global approaches in several cellular contexts have revealed that UPR regulates the expression of many miRNAs that play an important role in the regulation of life and death decisions during UPR. Here we show that expression of miR-424(322)-503 cluster is downregulated during UPR. IRE1 inhibitor (4 μ8C) and deficiency of XBP1 had no effect on downregulation of miR-424(322)-503 during UPR. Treatment of cells with CCT030312, a selective activator of EIF2AK3/PERK signalling, leads to the downregulation of miR-424(322)-503 expression. The repression of miR-424(322)-503 cluster during conditions of ER stress is compromised in PERK-deficient MEFs. miR-424 regulates the expression of ATF6 via a miR-424 binding site in its 3′ UTR and attenuates the ATF6 transcriptional activity during UPR. Further miR-424 had no effect on IRE1-XBP1 axis but enhanced the regulated IRE1-dependent decay (RIDD). Our results suggest that miR-424 constitutes an obligatory fine-tuning mechanism where PERK-mediated downregulation of miR-424(322)-503 cluster regulates optimal activation of IRE1 and ATF6 during conditions of ER stress. PMID:26674075

  19. Enhancing signal to noise ratio by fine-tuning tapers of cladded/uncladded buffer rods in ultrasonic time domain reflectometry in smelters.

    PubMed

    Viumdal, Håkon; Mylvaganam, Saba

    2014-03-01

    Buffer rods (BR) as waveguides in ultrasonic time domain reflectometry (TDR) can somewhat extend the range of industrial applications of ultrasonics. Level, temperature and flow measurements involving elevated temperatures, corrosive fluids and generally harsh environments are some of the applications in which conventional ultrasonic transducers cannot be used directly in contact with the media. In such cases, BRs with some design modifications can make ultrasonic TDR measurements possible with limited success. This paper deals with TDR in conjunction with distance measurements in extremely hot fluids, using conventional ultrasonic transducers in combination with BRs. When using BRs in the ultrasonic measurement systems in extreme temperatures, problems associated with size and the material of the buffer, have to be addressed. The resonant frequency of the transducer and the relative size of the transducer with respect to the diameter of BR are also important parameters influencing the signal to noise ratio (SNR) of the signal processing system used in the ultrasonic TDR. This paper gives an overview of design aspects related to the BRs with special emphasis on tapers and cladding used on BRs. As protective cladding, zirconium oxide-yttrium oxide composite was used, with its proven thermal stability in withstanding temperatures in rocket and jet engines up to 1650 °C. In general a BR should guide the signals through to the medium and from and back to the transducer without excessive attenuation and at the same time not exacerbate the noise in the measurement system. The SNR is the decisive performance indicator to consider in the design of BR based ultrasonic TDR, along with appropriate transducer, with suitable size and operating frequency. This work presents and analyses results from extensive experiments related to fine-tuning both geometry of and signals in cladded/uncladded BRs used in high temperature ultrasonic TDR with focus on overall performance based on

  20. Fine Tuning of CaV1.3 Ca2+ Channel Properties in Adult Inner Hair Cells Positioned in the Most Sensitive Region of the Gerbil Cochlea

    PubMed Central

    Zampini, Valeria; Johnson, Stuart L.; Franz, Christoph; Knipper, Marlies; Holley, Matthew C.; Magistretti, Jacopo; Russo, Giancarlo; Marcotti, Walter; Masetto, Sergio

    2014-01-01

    Hearing relies on faithful signal transmission by cochlear inner hair cells (IHCs) onto auditory fibres over a wide frequency and intensity range. Exocytosis at IHC ribbon synapses is triggered by Ca2+ inflow through CaV1.3 (L-type) Ca2+ channels. We investigated the macroscopic (whole-cell) and elementary (cell-attached) properties of Ca2+ currents in IHCs positioned at the middle turn (frequency ∼2 kHz) of the adult gerbil cochlea, which is their most sensitive hearing region. Using near physiological recordings conditions (body temperature and a Na+ based extracellular solution), we found that the macroscopic Ca2+ current activates and deactivates very rapidly (time constant below 1 ms) and inactivates slowly and only partially. Single-channel recordings showed an elementary conductance of 15 pS, a sub-ms latency to first opening, and a very low steady-state open probability (Po: 0.024 in response to 500-ms depolarizing steps at ∼−18 mV). The value of Po was significantly larger (0.06) in the first 40 ms of membrane depolarization, which corresponds to the time when most Ca2+ channel openings occurred clustered in bursts (mean burst duration: 19 ms). Both the Po and the mean burst duration were smaller than those previously reported in high-frequency basal IHCs. Finally, we found that middle turn IHCs are likely to express about 4 times more Ca2+ channels per ribbon than basal cells. We propose that middle-turn IHCs finely-tune CaV1.3 Ca2+ channel gating in order to provide reliable information upon timing and intensity of lower-frequency sounds. PMID:25409445

  1. Multibeam Phased Array Antennas

    NASA Technical Reports Server (NTRS)

    Popovic, Zoya; Romisch, Stefania; Rondineau, Sebastien

    2004-01-01

    In this study, a new architecture for Ka-band multi-beam arrays was developed and demonstrated experimentally. The goal of the investigation was to demonstrate a new architecture that has the potential of reducing the cost as compared to standard expensive phased array technology. The goals of this specific part of the project, as stated in the yearly statement of work in the original proposal are: 1. Investigate bounds on performance of multi-beam lens arrays in terms of beamwidths, volume (size), isolation between beams, number of simultaneous beams, etc. 2. Design a small-scale array to demonstrate the principle. The array will be designed for operation around 3OGHz (Ka-band), with two 10-degree beamwidth beams. 3. Investigate most appropriate way to accomplish fine-tuning of the beam pointing within 5 degrees around the main beam pointing angle.

  2. Three-Dimensional Thermomechanical Simulation of Fine-Pitch High-Count Ball Grid Array Flip-Chip Assemblies

    NASA Astrophysics Data System (ADS)

    Kpobie, W.; Bonfoh, N.; Dreistadt, C.; Fendler, M.; Lipinski, P.

    2013-07-01

    Flip-chip technology is increasingly prevalent in electronics assembly [three-dimensional (3D) system-in-package] and is mainly used at fine pitch for manufacture of megapixel large focal-plane detector arrays. To estimate the reliability of these assemblies, numerical simulations based on finite-element methods appear to be the cheapest approach. However, very large assemblies contain more than one million solder bumps, and the optimization process of such structures through numerical simulations turns out to be a very time-consuming task. In many applications, the interconnection layer of such flip-chip assemblies consists of solder bumps embedded in epoxy filler. For such configurations, we propose an alternative approach, which consists in replacing this heterogeneous interconnection layer by a homogeneous equivalent material (HEM). A micromechanical model for the estimation of its equivalent thermoelastic properties has been developed. The obtained constitutive law of the HEM was then implemented in finite-element software (Abaqus®). Thermomechanical responses of tested assemblies submitted to loads corresponding to manufacturing conditions have been analyzed. The homogenization-localization process allowed estimation of the mean values of stresses and strains in each phase of the interconnection layer. To access more precisely the stress and strain fields in these phases, two models of structural zoom, taking into account the real solder bump geometry, have been tested. The obtained local stress and strain fields corroborate the experimentally observed damage initiation of the solder bumps.

  3. Inadequate fine-tuning of protein synthesis and failure of amino acid homeostasis following inhibition of the ATPase VCP/p97

    PubMed Central

    Parzych, K; Chinn, T M; Chen, Z; Loaiza, S; Porsch, F; Valbuena, G N; Kleijnen, M F; Karadimitris, A; Gentleman, E; Keun, H C; Auner, H W

    2015-01-01

    The cellular mechanisms that control protein degradation may constitute a non-oncogenic cancer cell vulnerability and, therefore, a therapeutic target. Although this proposition is supported by the clinical success of proteasome inhibitors in some malignancies, most cancers are resistant to proteasome inhibition. The ATPase valosin-containing protein (VCP; p97) is an essential regulator of protein degradation in multiple pathways and has emerged as a target for cancer therapy. We found that pharmacological depletion of VCP enzymatic activity with mechanistically different inhibitors robustly induced proteotoxic stress in solid cancer and multiple myeloma cells, including cells that were insensitive, adapted, or clinically resistant to proteasome inhibition. VCP inhibition had an impact on two key regulators of protein synthesis, eukaryotic initiation factor 2α (eIF2α) and mechanistic target of rapamycin complex 1 (mTORC1), and attenuated global protein synthesis. However, a block on protein translation that was itself cytotoxic alleviated stress signaling and reduced cell death triggered by VCP inhibition. Some of the proteotoxic effects of VCP depletion depended on the eIF2α phosphatase, protein phosphatase 1 regulatory subunit 15A (PPP1R15A)/PP1c, but not on mTORC1, although there appeared to be cross-talk between them. Thus, cancer cell death following VCP inhibition was linked to inadequate fine-tuning of protein synthesis and activity of PPP1R15A/PP1c. VCP inhibitors also perturbed intracellular amino acid levels, activated eukaryotic translation initiation factor 2α kinase 4 (EIF2AK4), and enhanced cellular dependence on amino acid supplies, consistent with a failure of amino acid homeostasis. Many of the observed effects of VCP inhibition differed from the effects triggered by proteasome inhibition or by protein misfolding. Thus, depletion of VCP enzymatic activity triggers cancer cell death in part through inadequate regulation of protein synthesis and

  4. Functional Characterization of MODY2 Mutations Highlights the Importance of the Fine-Tuning of Glucokinase and Its Role in Glucose Sensing

    PubMed Central

    García-Herrero, Carmen-María; Rubio-Cabezas, Oscar; Azriel, Sharona; Gutierrez-Nogués, Angel; Aragonés, Angel; Vincent, Olivier; Campos-Barros, Angel; Argente, Jesús; Navas, María-Angeles

    2012-01-01

    Glucokinase (GK) acts as a glucose sensor in the pancreatic beta-cell and regulates insulin secretion. Heterozygous mutations in the human GK-encoding GCK gene that reduce the activity index increase the glucose-stimulated insulin secretion threshold and cause familial, mild fasting hyperglycaemia, also known as Maturity Onset Diabetes of the Young type 2 (MODY2). Here we describe the biochemical characterization of five missense GK mutations: p.Ile130Thr, p.Asp205His, p.Gly223Ser, p.His416Arg and p.Ala449Thr. The enzymatic analysis of the corresponding bacterially expressed GST-GK mutant proteins show that all of them impair the kinetic characteristics of the enzyme. In keeping with their position within the protein, mutations p.Ile130Thr, p.Asp205His, p.Gly223Ser, and p.His416Arg strongly decrease the activity index of GK, affecting to one or more kinetic parameters. In contrast, the p.Ala449Thr mutation, which is located in the allosteric activator site, does not affect significantly the activity index of GK, but dramatically modifies the main kinetic parameters responsible for the function of this enzyme as a glucose sensor. The reduced Kcat of the mutant (3.21±0.28 s−1 vs 47.86±2.78 s−1) is balanced by an increased glucose affinity (S0.5 = 1.33±0.08 mM vs 7.86±0.09 mM) and loss of cooperativity for this substrate. We further studied the mechanism by which this mutation impaired GK kinetics by measuring the differential effects of several competitive inhibitors and one allosteric activator on the mutant protein. Our results suggest that this mutation alters the equilibrium between the conformational states of glucokinase and highlights the importance of the fine-tuning of GK and its role in glucose sensing. PMID:22291974

  5. Post-translational S-Nitrosylation Is an Endogenous Factor Fine Tuning the Properties of Human S100A1 Protein*

    PubMed Central

    Lenarčič Živković, Martina; Zaręba-Kozioł, Monika; Zhukova, Liliya; Poznański, Jarosław; Zhukov, Igor; Wysłouch-Cieszyńska, Aleksandra

    2012-01-01

    S100A1 is a member of the Ca2+-binding S100 protein family. It is expressed in brain and heart tissue, where it plays a crucial role as a modulator of Ca2+ homeostasis, energy metabolism, neurotransmitter release, and contractile performance. Biological effects of S100A1 have been attributed to its direct interaction with a variety of target proteins. The (patho)physiological relevance of S100A1 makes it an important molecular target for future therapeutic intervention. S-Nitrosylation is a post-translational modification of proteins, which plays a role in cellular signal transduction under physiological and pathological conditions. In this study, we confirmed that S100A1 protein is endogenously modified by Cys85 S-nitrosylation in PC12 cells, which are a well established model system for studying S100A1 function. We used isothermal calorimetry to show that S-nitrosylation facilitates the formation of Ca2+-loaded S100A1 at physiological ionic strength conditions. To establish the unique influence of the S-nitroso group, our study describes high resolution three-dimensional structures of human apo-S100A1 protein with the Cys85 thiol group in reduced and S-nitrosylated states. Solution structures of the proteins are based on NMR data obtained at physiological ionic strength. Comparative analysis shows that S-nitrosylation fine tunes the overall architecture of S100A1 protein. Although the typical S100 protein intersubunit four-helix bundle is conserved upon S-nitrosylation, the conformation of S100A1 protein is reorganized at the sites most important for target recognition (i.e. the C-terminal helix and the linker connecting two EF-hand domains). In summary, this study discloses cysteine S-nitrosylation as a new factor responsible for increasing functional diversity of S100A1 and helps explain the role of S100A1 as a Ca2+ signal transmitter sensitive to NO/redox equilibrium within cells. PMID:22989881

  6. Codon optimization of xylA gene for recombinant glucose isomerase production in Pichia pastoris and fed-batch feeding strategies to fine-tune bioreactor performance.

    PubMed

    Ata, Özge; Boy, Erdem; Güneş, Hande; Çalık, Pınar

    2015-05-01

    The objectives of this work are the optimization of the codons of xylA gene from Thermus thermophilus to enhance the production of recombinant glucose isomerase (rGI) in P. pastoris and to investigate the effects of feeding strategies on rGI production. Codons of xylA gene from T. thermophilus were optimized, ca. 30 % of the codons were replaced with those with higher frequencies according to the codon usage bias of P. pastoris, codon optimization resulted in a 2.4-fold higher rGI activity. To fine-tune bioreactor performance, fed-batch bioreactor feeding strategies were designed as continuous exponential methanol feeding with pre-calculated feeding rate based on the pre-determined specific growth rate, and fed-batch methanol-stat feeding. Six feeding strategies were designed, as follows: (S1) continuous exponential methanol- and pulse- sorbitol feeding; (S2) continuous exponential methanol- and peptone- feeding; (S3) continuous exponential methanol- and pulse- mannitol feeding; (S4) continuous exponential methanol- and peptone- feeding and pulse-mannitol feeding; (S5) methanol-stat feeding by keeping methanol concentration at 5 g L(-1); and, (S6) methanol-stat feeding by keeping methanol concentration at 5 g L(-1) and pulse-mannitol feeding. The highest cell and rGI activity was attained as 117 g L(-1) at t = 66 h and 32530 U L(-1) at t = 53 h, in strategy-S5. The use of the co-substrate mannitol does not increase the rGI activity in methanol-stat feeding, where 4.1-fold lower rGI activity was obtained in strategy-S6. The overall cell yield on total substrate was determined at t = 53 h as 0.21 g g(-1) in S5 strategy. PMID:25492311

  7. The role of Rabi splitting tuning in the dynamics of strongly coupled J-aggregates and surface plasmon polaritons in nanohole arrays.

    PubMed

    Wang, Hai; Toma, Andrea; Wang, Hai-Yu; Bozzola, Angelo; Miele, Ermanno; Haddadpour, Ali; Veronis, Georgios; De Angelis, Francesco; Wang, Lei; Chen, Qi-Dai; Xu, Huai-Liang; Sun, Hong-Bo; Zaccaria, Remo Proietti

    2016-07-21

    We have investigated the influence of Rabi splitting tuning on the dynamics of strongly coupled J-aggregate/surface plasmon polariton systems. In particular, the Rabi splitting was tuned by modifying the J-aggregate molecule concentration while a polaritonic system was provided by a nanostructure formed by holes array in a golden layer. From the periodic and concentration changes we have identified, through numerical and experimental steady-state analyses, the best geometrical configuration for maximizing Rabi splitting, which was then used for transient absorption measurements. It was found that in transient absorption spectra, under upper band excitation, two bleaching peaks appear when a nanostructured polaritonic pattern is used. Importantly, their reciprocal distance increases upon increase of J-aggregate concentration, a result confirmed by steady-state analysis. In a similar manner it was also found that the lifetime of the upper band is intimately related to the coupling strength. In particular, we argue that with strong coupling strength, i.e. high J-aggregate concentration, a short lifetime of the upper band has to be expected due to the suppression of the bottleneck effect. This result supports the idea that the dynamics of hybrid systems is profoundly dependent on Rabi splitting. PMID:27350590

  8. The role of Rabi splitting tuning in the dynamics of strongly coupled J-aggregates and surface plasmon polaritons in nanohole arrays

    NASA Astrophysics Data System (ADS)

    Wang, Hai; Toma, Andrea; Wang, Hai-Yu; Bozzola, Angelo; Miele, Ermanno; Haddadpour, Ali; Veronis, Georgios; de Angelis, Francesco; Wang, Lei; Chen, Qi-Dai; Xu, Huai-Liang; Sun, Hong-Bo; Zaccaria, Remo Proietti

    2016-07-01

    We have investigated the influence of Rabi splitting tuning on the dynamics of strongly coupled J-aggregate/surface plasmon polariton systems. In particular, the Rabi splitting was tuned by modifying the J-aggregate molecule concentration while a polaritonic system was provided by a nanostructure formed by holes array in a golden layer. From the periodic and concentration changes we have identified, through numerical and experimental steady-state analyses, the best geometrical configuration for maximizing Rabi splitting, which was then used for transient absorption measurements. It was found that in transient absorption spectra, under upper band excitation, two bleaching peaks appear when a nanostructured polaritonic pattern is used. Importantly, their reciprocal distance increases upon increase of J-aggregate concentration, a result confirmed by steady-state analysis. In a similar manner it was also found that the lifetime of the upper band is intimately related to the coupling strength. In particular, we argue that with strong coupling strength, i.e. high J-aggregate concentration, a short lifetime of the upper band has to be expected due to the suppression of the bottleneck effect. This result supports the idea that the dynamics of hybrid systems is profoundly dependent on Rabi splitting.

  9. Fine-tuning of age integrating magnetostratigraphy, radiocarbon dating, and carbonate cyclicity: Example of lacustrine sediments from Heqing basin (Yunnan, China) covering the past 1 Myr

    NASA Astrophysics Data System (ADS)

    Hu, Shouyun; Goddu, Srinivasa Rao; Appel, Erwin; Verosub, Ken

    2007-05-01

    convincing Milankovitch spectrum of whole-core carbonate data. The Fourier spectra of whole-core carbonate and susceptibility time series calibrated by the optimum age model show clear Milankovitch cyclicities (95, 41, 23, and 19 kyr) indicating that a global palaeoclimatic signal is recorded. According to this result the Heqing core spans almost the complete past 1 Myr (5-1001 ka). Detailed depth-to-age conversion is listed. The optimum age model can be used as a fine-tuned time basis for interpreting the existing data set of palaeoclimatic proxies which have been already measured for this sequence.

  10. Precise Modulation of the Breathing Behavior and Pore Surface in Zr-MOFs by Reversible Post-Synthetic Variable-Spacer Installation to Fine-Tune the Expansion Magnitude and Sorption Properties.

    PubMed

    Chen, Cheng-Xia; Wei, Zhangwen; Jiang, Ji-Jun; Fan, Yan-Zhong; Zheng, Shao-Ping; Cao, Chen-Chen; Li, Yu-Hao; Fenske, Dieter; Su, Cheng-Yong

    2016-08-16

    To combine flexibility and modifiability towards a more controllable complexity of MOFs, a post-synthetic variable-spacer installation (PVSI) strategy is used to implement kinetic installation/ uninstallation of secondary ligands into/from a robust yet flexible proto-Zr-MOF. This PVSI process features precise positioning of spacers with different length, size, number, and functionality, enabling accurate fixation of successive breathing stages and fine-tuning of pore surface. It shows unprecedented synthetic tailorability to create complicated MOFs in a predictable way for property modification, for example, CO2 and R22 adsorption/separation, thermal/chemical stability, and extended breathing behavior. PMID:27405047