Science.gov

Sample records for intrinsic phase response

  1. Intrinsic response of polymer liquid crystals in photochemical phase transition

    SciTech Connect

    Ikeda, Tomiki; Sasaki, Takeo; Kim, Haengboo )

    1991-01-24

    Time-resolved measurements were performed on the photochemically induced isothermal phase transition of polymer liquid crystals (PLC) with mesogenic side chains of phenyl benzoate (PAPB3) and cyanobiphenyl (PACB3) under conditions wherein the photochemical reaction of the doped photoresponsive molecule (4-butyl-4-{prime}-methoxyazobenzene, BMAB) was completed within {approximately} 10 ns, and the subsequent phase transition of the matrix PLC from nematic (N) to isotropic (I) state was followed by time-resolved measurements of the birefringence of the system. Formation of a sufficient amount of the cis isomer of BMAB with a single pulse of a laser lowered the N-I phase transition temperature of the mixture, inducing the N-I phase transition of PLCs isothermally in a time range of {approximately} 200 ms. This time range is comparable to that of low molecular weight liquid crystals, indicating that suppression in mobility of mesogens in PLCs does not affect significantly the thermodynamically controlled process.

  2. Intrinsic topological superfluidity - fluctuations and response

    NASA Astrophysics Data System (ADS)

    Levin, K.; Wu, Chien-Te; Anderson, Brandon; Boyack, Rufus

    Recent interest in topological superconductivity is based primarily on exploiting proximity effects to obtain this important phase. However, in cold gases it is possible to contemplate ``intrinsic'' topological superfluidity produced with a synthetic spin-orbit coupling and Zeeman field. It is important for such future experiments to establish how low in temperature one needs to go to reach the ordered phase. Similarly, it will be helpful to have a probe of the normal (pseudogap) phase to determine if the ultimate superfluid order will be topological or trivial. In this talk, we address these issues by considering fluctuation effects in such a superfluid, and calculate the critical transition temperature and response functions. We see qualitative signatures of topological superfluidity in spin and charge response functions. We also explore the suppression of superfluidity due to fluctuations, and importantly find that the temperature scales necessary to reach topological superfluidity are reasonably accessible

  3. Intrinsic Response Time of Graphene Photodetectors

    PubMed Central

    2011-01-01

    Graphene-based photodetectors are promising new devices for high-speed optoelectronic applications. However, despite recent efforts it is not clear what determines the ultimate speed limit of these devices. Here, we present measurements of the intrinsic response time of metal–graphene–metal photodetectors with monolayer graphene using an optical correlation technique with ultrashort laser pulses. We obtain a response time of 2.1 ps that is mainly given by the short lifetime of the photogenerated carriers. This time translates into a bandwidth of ∼262 GHz. Moreover, we investigate the dependence of the response time on gate voltage and illumination laser power. PMID:21627096

  4. Adaptive Responses Limited by Intrinsic Noise

    PubMed Central

    Shankar, Prabhat; Nishikawa, Masatoshi; Shibata, Tatsuo

    2015-01-01

    Sensory systems have mechanisms to respond to the external environment and adapt to them. Such adaptive responses are effective for a wide dynamic range of sensing and perception of temporal change in stimulus. However, noise generated by the adaptation system itself as well as extrinsic noise in sensory inputs may impose a limit on the ability of adaptation systems. The relation between response and noise is well understood for equilibrium systems in the form of fluctuation response relation. However, the relation for nonequilibrium systems, including adaptive systems, are poorly understood. Here, we systematically explore such a relation between response and fluctuation in adaptation systems. We study the two network motifs, incoherent feedforward loops (iFFL) and negative feedback loops (nFBL), that can achieve perfect adaptation. We find that the response magnitude in adaption systems is limited by its intrinsic noise, implying that higher response would have higher noise component as well. Comparing the relation of response and noise in iFFL and nFBL, we show that whereas iFFL exhibits adaptation over a wider parameter range, nFBL offers higher response to noise ratio than iFFL. We also identify the condition that yields the upper limit of response for both network motifs. These results may explain the reason of why nFBL seems to be more abundant in nature for the implementation of adaption systems. PMID:26305221

  5. Quantum phases in intrinsic Josephson junctions: Quantum magnetism analogy

    NASA Astrophysics Data System (ADS)

    Machida, Masahiko; Kobayashi, Keita; Koyama, Tomio

    2013-08-01

    We explore quantum phases in intrinsic Josephson junction (IJJ) stacks, whose in-plane area is so small that the capacitive coupling has a dominant role in the superconducting phase dynamics. In such cases, the effective Hamiltonian for the superconducting phase can be mapped onto that of one-dimensional ferromagnetically-interacting spin model, whose spin length S depends on the magnitude of the on-site Coulomb repulsion. The ferromagnetic model for IJJ’s prefers synchronized quantum features in contrast to the antiferromagnetically-interacting model in the conventional Josephson junction arrays.

  6. Intrinsic response of crystals to pure dilatation

    NASA Astrophysics Data System (ADS)

    Wang, Jinghan; Yip, S.; Phillpot, S.; Wolf, D.

    The response of an f.c.c. lattice with Lennard-Jones interaction under symmetric lattice extension has been studied by Monte Carlo simulation at several temperatures. The critical strain at which the crystal undergoes a structural change is found to be well predicted by the mechanical stability limit expressed in terms of either the elastic constants or the bulk modulus. At low temperature (reduced temperature T = 0.125), lattice decohesion is observed in the form of cleavage fracture, whereas at higher temperature (T = 0.3) the strained system deforms by cavitation with some degree of local plasticity. At still higher temperature (T = 0.5) the lattice undergoes homogeneous disordering with all the attendant characteristics of melting.

  7. Intrinsic fluctuations and driven response of insect swarms

    NASA Astrophysics Data System (ADS)

    Ni, Rui; Puckett, James G.; Dufresne, Eric R.; Ouellette, Nicholas T.

    2015-03-01

    Much of our understanding of collective behaviour in social animals comes from passive observations of animal groups. To understand the group dynamics fully, however, we must also characterize the response of animal aggregations to disturbances. Using three-dimensional particle tracking, we study both the intrinsic fluctuations of laboratory swarms of the non-biting midge Chironomus riparius and the response of the swarms to controlled external perturbations: the amplitude-modulated sound of male midge wingbeats. Although these perturbations have an insignificant effect on the behavior of individuals, we find that they can have a strong impact on the collective movement. Intriguingly, the response of the swarm is similar reminiscent to of that of a passive equilibrium system to an external driving force, with microscopic fluctuations underlying combining to produce a macroscopic linear response over a wide range of driving frequencies.

  8. Intrinsic Fluctuations and Driven Response of Insect Swarms

    NASA Astrophysics Data System (ADS)

    Ni, Rui; Puckett, James G.; Dufresne, Eric R.; Ouellette, Nicholas T.

    2015-09-01

    Animals of all sizes form groups, as acting together can convey advantages over acting alone; thus, collective animal behavior has been identified as a promising template for designing engineered systems. However, models and observations have focused predominantly on characterizing the overall group morphology, and often focus on highly ordered groups such as bird flocks. We instead study a disorganized aggregation (an insect mating swarm), and compare its natural fluctuations with the group-level response to an external stimulus. We quantify the swarm's frequency-dependent linear response and its spectrum of intrinsic fluctuations, and show that the ratio of these two quantities has a simple scaling with frequency. Our results provide a new way of comparing models of collective behavior with experimental data.

  9. Intrinsic fluctuations and driven response of insect swarms.

    PubMed

    Ni, Rui; Puckett, James G; Dufresne, Eric R; Ouellette, Nicholas T

    2015-09-11

    Animals of all sizes form groups, as acting together can convey advantages over acting alone; thus, collective animal behavior has been identified as a promising template for designing engineered systems. However, models and observations have focused predominantly on characterizing the overall group morphology, and often focus on highly ordered groups such as bird flocks. We instead study a disorganized aggregation (an insect mating swarm), and compare its natural fluctuations with the group-level response to an external stimulus. We quantify the swarm's frequency-dependent linear response and its spectrum of intrinsic fluctuations, and show that the ratio of these two quantities has a simple scaling with frequency. Our results provide a new way of comparing models of collective behavior with experimental data. PMID:26406859

  10. Broadband macroscopic cortical oscillations emerge from intrinsic neuronal response failures

    PubMed Central

    Goldental, Amir; Vardi, Roni; Sardi, Shira; Sabo, Pinhas; Kanter, Ido

    2015-01-01

    Broadband spontaneous macroscopic neural oscillations are rhythmic cortical firing which were extensively examined during the last century, however, their possible origination is still controversial. In this work we show how macroscopic oscillations emerge in solely excitatory random networks and without topological constraints. We experimentally and theoretically show that these oscillations stem from the counterintuitive underlying mechanism—the intrinsic stochastic neuronal response failures (NRFs). These NRFs, which are characterized by short-term memory, lead to cooperation among neurons, resulting in sub- or several- Hertz macroscopic oscillations which coexist with high frequency gamma oscillations. A quantitative interplay between the statistical network properties and the emerging oscillations is supported by simulations of large networks based on single-neuron in-vitro experiments and a Langevin equation describing the network dynamics. Results call for the examination of these oscillations in the presence of inhibition and external drives. PMID:26578893

  11. Critical Evaluation of Ayurvedic Plants for Stimulating Intrinsic Antioxidant Response

    PubMed Central

    Shukla, Sunil Dutt; Bhatnagar, Maheep; Khurana, Sukant

    2012-01-01

    Oxidative damage caused by free radicals plays an important role in the causation and progression of many diseases, including aging. Free-radical damage is countered by many mechanisms, including both active antioxidant enzymatic activity in our body and passive antioxidants. Antioxidant response of our body can accommodate increased oxidative damage in diseased states to a level but beyond that level, additional antioxidants are required to combat the increased stress. Apart from the regular dietary sources of antioxidants, many traditional herbal medicines demonstrate a potential to boost antioxidant activity. Rasayana chikitsa that deals with rejuvenation and revitalization is a branch of the Indian traditional medical system of ayurveda. We review some select herbs described in rasayana chikitsa that have been assessed by modern means for stimulating intrinsic antioxidant responses in humans. A critical evaluation of rasayana chikitsa will likely provide urgently needed, actual stimulants of our physiological antioxidant responses and not just more passive antioxidants to add to an already large catalog. PMID:22855669

  12. Intrinsic spin hall effect induced by quantum phase transition in HgCdTe quantum wells.

    PubMed

    Yang, Wen; Chang, Kai; Zhang, Shou-Cheng

    2008-02-01

    The spin Hall effect can be induced by both extrinsic impurity scattering and intrinsic spin-orbit coupling in the electronic structure. The HgTe/CdTe quantum well has a quantum phase transition where the electronic structure changes from normal to inverted. We show that the intrinsic spin Hall effect of the conduction band vanishes on the normal side, while it is finite on the inverted side. By tuning the Cd content, the well width, or the bias electric field across the quantum well, the intrinsic spin Hall effect can be switched on or off and tuned into resonance under experimentally accessible conditions. PMID:18352404

  13. Intrinsic Spin Hall Effect Induced by Quantum Phase Transition in HgCdTe Quantum Wells

    SciTech Connect

    Yang, Wen; Chang, Kai; Zhang, Shou-Cheng; /Stanford U., Phys. Dept.

    2010-03-19

    Spin Hall effect can be induced both by the extrinsic impurity scattering and by the intrinsic spin-orbit coupling in the electronic structure. The HgTe/CdTe quantum well has a quantum phase transition where the electronic structure changes from normal to inverted. We show that the intrinsic spin Hall effect of the conduction band vanishes on the normal side, while it is finite on the inverted side. This difference gives a direct mechanism to experimentally distinguish the intrinsic spin Hall effect from the extrinsic one.

  14. Polymerase chain reaction with phase change as intrinsic thermal control

    NASA Astrophysics Data System (ADS)

    Hsieh, Yi-Fan; Yonezawa, Eri; Kuo, Long-Sheng; Yeh, Shiou-Hwei; Chen, Pei-Jer; Chen, Ping-Hei

    2013-04-01

    This research demonstrated that without any external temperature controller, the capillary convective polymerase chain reaction (ccPCR) powered by a candle can operate with the help of phase change. The candle ccPCR system productively amplified hepatitis B virus 122 base-pairs DNA fragment. The detection sensitivity can achieve at an initial DNA concentration to 5 copies per reaction. The results also show that the candle ccPCR system can operate functionally even the ambient temperature varies from 7 °C to 45 °C. These features imply that the candle ccPCR system can provide robust medical detection services.

  15. Fingerprints of intrinsic phase separation: magnetically doped two-dimensional electron gas.

    PubMed

    Terletska, H; Dobrosavljević, V

    2011-05-01

    In addition to Anderson and Mott localization, intrinsic phase separation has long been advocated as the third fundamental mechanism controlling the doping-driven metal-insulator transitions. In electronic system, where charge neutrality precludes global phase separation, it may lead to various inhomogeneous states and dramatically affect transport. Here we theoretically predict the precise experimental signatures of such phase separation-driven metal-insulator transitions. We show that anomalous transport is expected in an intermediate regime around the transition, displaying very strong temperature and magnetic field dependence but very weak density dependence. Our predictions find striking agreement with recent experiments on Mn-doped CdTe quantum wells, a system where we identify the microscopic origin for intrinsic phase separation. PMID:21635108

  16. Plastic Change along the Intact Crossed Pathway in Acute Phase of Cerebral Ischemia Revealed by Optical Intrinsic Signal Imaging

    PubMed Central

    Guo, Xiaoli; He, Yongzhi; Lu, Hongyang; Li, Yao; Su, Xin; Jiang, Ying; Tong, Shanbao

    2016-01-01

    The intact crossed pathway via which the contralesional hemisphere responds to the ipsilesional somatosensory input has shown to be affected by unilateral stroke. The aim of this study was to investigate the plasticity of the intact crossed pathway in response to different intensities of stimulation in a rodent photothrombotic stroke model. Using optical intrinsic signal imaging, an overall increase of the contralesional cortical response was observed in the acute phase (≤48 hours) after stroke. In particular, the contralesional hyperactivation is more prominent under weak stimulations, while a strong stimulation would even elicit a depressed response. The results suggest a distinct stimulation-response pattern along the intact crossed pathway after stroke. We speculate that the contralesional hyperactivation under weak stimulations was due to the reorganization for compensatory response to the weak ipsilateral somatosensory input. PMID:27144032

  17. Sequence heuristics to encode phase behaviour in intrinsically disordered protein polymers

    NASA Astrophysics Data System (ADS)

    Quiroz, Felipe García; Chilkoti, Ashutosh

    2015-11-01

    Proteins and synthetic polymers that undergo aqueous phase transitions mediate self-assembly in nature and in man-made material systems. Yet little is known about how the phase behaviour of a protein is encoded in its amino acid sequence. Here, by synthesizing intrinsically disordered, repeat proteins to test motifs that we hypothesized would encode phase behaviour, we show that the proteins can be designed to exhibit tunable lower or upper critical solution temperature (LCST and UCST, respectively) transitions in physiological solutions. We also show that mutation of key residues at the repeat level abolishes phase behaviour or encodes an orthogonal transition. Furthermore, we provide heuristics to identify, at the proteome level, proteins that might exhibit phase behaviour and to design novel protein polymers consisting of biologically active peptide repeats that exhibit LCST or UCST transitions. These findings set the foundation for the prediction and encoding of phase behaviour at the sequence level.

  18. Sequence heuristics to encode phase behaviour in intrinsically disordered protein polymers

    PubMed Central

    Quiroz, Felipe García; Chilkoti, Ashutosh

    2015-01-01

    Proteins and synthetic polymers that undergo aqueous phase transitions mediate self-assembly in nature and in man-made material systems. Yet little is known about how the phase behaviour of a protein is encoded in its amino acid sequence. Here, by synthesizing intrinsically disordered, repeat proteins to test motifs that we hypothesized would encode phase behaviour, we show that the proteins can be designed to exhibit tunable lower or upper critical solution temperature (LCST and UCST, respectively) transitions in physiological solutions. We also show that mutation of key residues at the repeat level abolishes phase behaviour or encodes an orthogonal transition. Furthermore, we provide heuristics to identify, at the proteome level, proteins that might exhibit phase behaviour and to design novel protein polymers consisting of biologically active peptide repeats that exhibit LCST or UCST transitions. These findings set the foundation for the prediction and encoding of phase behaviour at the sequence level. PMID:26390327

  19. Sequence heuristics to encode phase behaviour in intrinsically disordered protein polymers.

    PubMed

    Quiroz, Felipe García; Chilkoti, Ashutosh

    2015-11-01

    Proteins and synthetic polymers that undergo aqueous phase transitions mediate self-assembly in nature and in man-made material systems. Yet little is known about how the phase behaviour of a protein is encoded in its amino acid sequence. Here, by synthesizing intrinsically disordered, repeat proteins to test motifs that we hypothesized would encode phase behaviour, we show that the proteins can be designed to exhibit tunable lower or upper critical solution temperature (LCST and UCST, respectively) transitions in physiological solutions. We also show that mutation of key residues at the repeat level abolishes phase behaviour or encodes an orthogonal transition. Furthermore, we provide heuristics to identify, at the proteome level, proteins that might exhibit phase behaviour and to design novel protein polymers consisting of biologically active peptide repeats that exhibit LCST or UCST transitions. These findings set the foundation for the prediction and encoding of phase behaviour at the sequence level. PMID:26390327

  20. Theory of phase dynamics in intrinsic Josephson junctions with multigap superconducting layers

    NASA Astrophysics Data System (ADS)

    Ota, Y.; Machida, M.; Koyama, T.

    2011-11-01

    We construct a theory of dynamical behavior in intrinsic Josephson junction stacks with multigap superconducting layers. The theory predicts the existence of two kinds of phase modes, one of which is the Josephson-plasma mode and other of which is the Leggett’s mode. We discuss a cooperative phenomena induced by inter-band Josephson coupling in addition to capacitive and inductive couplings between the superconducting layers.

  1. Slow Conductances Could Underlie Intrinsic Phase-Maintaining Properties of Isolated Lobster (Panulirus interruptus) Pyloric Neurons

    PubMed Central

    Hooper, Scott L.; Buchman, Einat; Weaver, Adam L.; Thuma, Jeffrey B.; Hobbs, Kevin H.

    2009-01-01

    The rhythmic pyloric network of the lobster stomatogastric system approximately maintains phase (that is, the burst durations and durations between the bursts of its neurons change proportionally) when network cycle period is altered by current injection into the network pacemaker (Hooper, 1997a,b). When isolated from the network and driven by rhythmic hyperpolarizing current pulses, the delay to firing after each pulse of at least one network neuron type (Pyloric, PY) varies in a phase-maintaining manner when cycle period is varied (Hooper, 1998). These variations require PY neurons to have intrinsic mechanisms that respond to changes in neuron activity on time scales at least as long as two seconds. Slowly activating and deactivating conductances could provide such a mechanism. We tested this possibility by building models containing various slow conductances. This work showed that such conductances could indeed support intrinsic phase-maintenance and we show here results for one such conductance, a slow potassium conductance. These conductances supported phase maintenance because their mean activation level changed, hence altering neuron post-inhibition firing delay, when the rhythmic input to the neuron changed. Switching the sign of the dependence of slow conductance activation and deactivation on membrane potential resulted in neuron delays switching to change in an anti-phase maintaining manner. These data suggest that slow conductances or similar slow processes such as changes in intracellular Ca2+ concentration could underlie phase maintenance in pyloric network neurons. PMID:19211890

  2. Diminished neural responses predict enhanced intrinsic motivation and sensitivity to external incentive.

    PubMed

    Marsden, Karen E; Ma, Wei Ji; Deci, Edward L; Ryan, Richard M; Chiu, Pearl H

    2015-06-01

    The duration and quality of human performance depend on both intrinsic motivation and external incentives. However, little is known about the neuroscientific basis of this interplay between internal and external motivators. Here, we used functional magnetic resonance imaging to examine the neural substrates of intrinsic motivation, operationalized as the free-choice time spent on a task when this was not required, and tested the neural and behavioral effects of external reward on intrinsic motivation. We found that increased duration of free-choice time was predicted by generally diminished neural responses in regions associated with cognitive and affective regulation. By comparison, the possibility of additional reward improved task accuracy, and specifically increased neural and behavioral responses following errors. Those individuals with the smallest neural responses associated with intrinsic motivation exhibited the greatest error-related neural enhancement under the external contingency of possible reward. Together, these data suggest that human performance is guided by a "tonic" and "phasic" relationship between the neural substrates of intrinsic motivation (tonic) and the impact of external incentives (phasic). PMID:25348668

  3. Supramolecular reactivity in the gas phase: investigating the intrinsic properties of non-covalent complexes.

    PubMed

    Cera, Luca; Schalley, Christoph A

    2014-03-21

    The high vacuum inside a mass spectrometer offers unique conditions to broaden our view on the reactivity of supramolecules. Because dynamic exchange processes between complexes are efficiently suppressed, the intrinsic and intramolecular reactivity of the complexes of interest is observed. Besides this, the significantly higher strength of non-covalent interactions in the absence of competing solvent allows processes to occur that are unable to compete in solution. The present review highlights a series of examples illustrating different aspects of supramolecular gas-phase reactivity ranging from the dissociation and formation of covalent bonds in non-covalent complexes through the reactivity in the restricted inner phase of container molecules and step-by-step mechanistic studies of organocatalytic reaction cycles to cage contraction reactions, processes induced by electron capture, and finally dynamic molecular motion within non-covalent complexes as unravelled by hydrogen-deuterium exchange processes performed in the gas phase. PMID:24435245

  4. Uncovering the intrinsic size dependence of hydriding phase transformations in nanocrystals

    NASA Astrophysics Data System (ADS)

    Bardhan, Rizia; Hedges, Lester O.; Pint, Cary L.; Javey, Ali; Whitelam, Stephen; Urban, Jeffrey J.

    2013-10-01

    A quantitative understanding of nanocrystal phase transformations would enable more efficient energy conversion and catalysis, but has been hindered by difficulties in directly monitoring well-characterized nanoscale systems in reactive environments. We present a new in situ luminescence-based probe enabling direct quantification of nanocrystal phase transformations, applied here to the hydriding transformation of palladium nanocrystals. Our approach reveals the intrinsic kinetics and thermodynamics of nanocrystal phase transformations, eliminating complications of substrate strain, ligand effects and external signal transducers. Clear size-dependent trends emerge in nanocrystals long accepted to be bulk-like in behaviour. Statistical mechanical simulations show these trends to be a consequence of nanoconfinement of a thermally driven, first-order phase transition: near the phase boundary, critical nuclei of the new phase are comparable in size to the nanocrystal itself. Transformation rates are then unavoidably governed by nanocrystal dimensions. Our results provide a general framework for understanding how nanoconfinement fundamentally impacts broad classes of thermally driven solid-state phase transformations relevant to hydrogen storage, catalysis, batteries and fuel cells.

  5. An effect of temperature distribution on terahertz phase dynamics in intrinsic Josephson junctions

    NASA Astrophysics Data System (ADS)

    Asai, Hidehiro; Kawabata, Shiro

    2013-11-01

    In this study, we numerically calculate the temperature distribution and the THz phase dynamics in the mesa-structured intrinsic Josephson junctions (IJJs) using the thermal diffusion equation and the Sine-Gordon equation. We observe that the temperature distribution has a broad peak around the center region of the IJJ mesa. Under a high external current, a “hot spot” where the temperature is locally higher than the superconducting critical temperature appears around this region. The transverse Josephson plasma wave is strongly excited by the inhomogeneous temperature distribution in the mesa. This gives rise to intense THz emission.

  6. Extrinsic and Intrinsic Responses to Environmental Change: Insights from Terrestrial Paleoecological Archives

    NASA Astrophysics Data System (ADS)

    Seddon, A. W. R.; Mackay, A. W.

    2015-12-01

    Current understanding of ecological behaviour indicates that systems can experience sudden and abrupt changes in state, driven either by a large external change in environmental conditions (extrinsically forced), or the result of a set local feedbacks and site-specific interactions (intrinsically mediated responses). Responses mediated by intrinsic processes are notoriously diffi- cult to predict, they can occur as slow environmental variables gradually erode the resilience of the system eventually resulting in threshold transitions between alternative stable states. Finding ways to identify, model and predict such complex ecosystem behavior has been identified as a priority research challenge for both ecology and paleoecology. The paleoecological record can play a role in understanding the processes behind abrupt ecological change because it enables the reconstruction of processes occurring over decadal-centennial timescales or longer. Therefore, paleoecological data can be used to identify the existence of ecological thresholds and to investigate the environmental processes that can lead to loss of resilience and abrupt transitions between alternate states. In addition, incidences of abrupt vegetation changes in the past can serve as palaeoecological model systems; analogues of abrupt dynamics which can be used to test theories surrounding ecological responses to climate change. Here, I present examples from a range of terrestrial ecosystems (Holocene environmental changes from a coastal lagoon in the Galapagos Islands; Northern European vegetation changes since the last deglaciation; the North American hemlock decline) demonstrating evidence of abrupt ecosystem change. For each system I present a set of statistical techniques tailored to distin- guish between extrinsic versus intrinsically mediated ecological responses. Examples are provided from both single sites (i.e. landscape scale) and multiple sites (regional-continental scale). These techniques provide a

  7. Microfluidic SAXS Study of Lamellar and Multilamellar Vesicle Phases of Linear Sodium Alkylbenzenesulfonate Surfactant with Intrinsic Isomeric Distribution.

    PubMed

    Poulos, Andreas S; Nania, Manuela; Lapham, Paul; Miller, Ruhina M; Smith, Andrew J; Tantawy, Hossam; Caragay, Joel; Gummel, Jérémie; Ces, Oscar; Robles, Eric S J; Cabral, João T

    2016-06-14

    The structure and flow behavior of a concentrated aqueous solution (45 wt %) of the ubiquitous linear sodium alkylbenzenesulfonate (NaLAS) surfactant is investigated by microfluidic small-angle X-ray scattering (SAXS) at 70 °C. NaLAS is an intrinsically complex mixture of over 20 surfactant molecules, presenting coexisting micellar (L1) and lamellar (Lα) phases. Novel microfluidic devices were fabricated to ensure pressure and thermal resistance, ability to handle viscous fluids, and low SAXS background. Polarized light optical microscopy showed that the NaLAS solution exhibits wall slip in microchannels, with velocity profiles approaching plug flow. Microfluidic SAXS demonstrated the structural spatial heterogeneity of the system with a characteristic length scale of 50 nL. Using a statistical flow-SAXS analysis, we identified the micellar phase and multiple coexisting lamellar phases with a continuous distribution of d spacings between 37.5 and 39.5 Å. Additionally, we showed that the orientation of NaLAS lamellar phases is strongly affected by a single microfluidic constriction. The bilayers align parallel to the velocity field upon entering a constriction and perpendicular to it upon exiting. On the other hand, multilamellar vesicle phases are not affected under the same flow conditions. Our results demonstrate that despite the compositional complexity inherent to NaLAS, microfluidic SAXS can rigorously elucidate its structure and flow response. PMID:27196820

  8. Terahertz Responses of Intrinsic Josephson Junctions in High T{sub C} Superconductors

    SciTech Connect

    Wang, H. B.; Wu, P. H.; Yamashita, T.

    2001-09-03

    High frequency responses of intrinsic Josephson junctions up to 2.5THz, including the observation of Shapiro steps under various conditions, are reported and discussed in this Letter. The sample was an array of intrinsic Josephson junctions singled out from inside a high T{sub C} superconducting Bi{sub 2}Sr {sub 2}CaCu{sub 2}O{sub 8+x} single crystal, with a bow-tie antenna integrated to it. The number of junctions in the array was controllable, the junctions were homogeneous, the distribution of applied irradiation among the junctions was even, and the junctions could synchronously respond to high frequency irradiation.

  9. Association of intrinsic circadian period with morningness-eveningness, usual wake time, and circadian phase

    NASA Technical Reports Server (NTRS)

    Duffy, J. F.; Rimmer, D. W.; Czeisler, C. A.

    2001-01-01

    The biological basis of preferences for morning or evening activity patterns ("early birds" and "night owls") has been hypothesized but has remained elusive. The authors reported that, compared with evening types, the circadian pacemaker of morning types was entrained to an earlier hour with respect to both clock time and wake time. The present study explores a chronobiological mechanism by which the biological clock of morning types may be set to an earlier hour. Intrinsic period, a fundamental property of the circadian system, was measured in a month-long inpatient study. A subset of participants also had their circadian phase assessed. Participants completed a morningness-eveningness questionnaire before study. Circadian period was correlated with morningness-eveningness, circadian phase, and wake time, demonstrating that a fundamental property of the circadian pacemaker is correlated with the behavioral trait of morningness-eveningness.

  10. Complete Firing-Rate Response of Neurons with Complex Intrinsic Dynamics.

    PubMed

    Puelma Touzel, Maximilian; Wolf, Fred

    2015-12-01

    The response of a neuronal population over a space of inputs depends on the intrinsic properties of its constituent neurons. Two main modes of single neuron dynamics-integration and resonance-have been distinguished. While resonator cell types exist in a variety of brain areas, few models incorporate this feature and fewer have investigated its effects. To understand better how a resonator's frequency preference emerges from its intrinsic dynamics and contributes to its local area's population firing rate dynamics, we analyze the dynamic gain of an analytically solvable two-degree of freedom neuron model. In the Fokker-Planck approach, the dynamic gain is intractable. The alternative Gauss-Rice approach lifts the resetting of the voltage after a spike. This allows us to derive a complete expression for the dynamic gain of a resonator neuron model in terms of a cascade of filters on the input. We find six distinct response types and use them to fully characterize the routes to resonance across all values of the relevant timescales. We find that resonance arises primarily due to slow adaptation with an intrinsic frequency acting to sharpen and adjust the location of the resonant peak. We determine the parameter regions for the existence of an intrinsic frequency and for subthreshold and spiking resonance, finding all possible intersections of the three. The expressions and analysis presented here provide an account of how intrinsic neuron dynamics shape dynamic population response properties and can facilitate the construction of an exact theory of correlations and stability of population activity in networks containing populations of resonator neurons. PMID:26720924

  11. Complete Firing-Rate Response of Neurons with Complex Intrinsic Dynamics

    PubMed Central

    Puelma Touzel, Maximilian; Wolf, Fred

    2015-01-01

    The response of a neuronal population over a space of inputs depends on the intrinsic properties of its constituent neurons. Two main modes of single neuron dynamics–integration and resonance–have been distinguished. While resonator cell types exist in a variety of brain areas, few models incorporate this feature and fewer have investigated its effects. To understand better how a resonator’s frequency preference emerges from its intrinsic dynamics and contributes to its local area’s population firing rate dynamics, we analyze the dynamic gain of an analytically solvable two-degree of freedom neuron model. In the Fokker-Planck approach, the dynamic gain is intractable. The alternative Gauss-Rice approach lifts the resetting of the voltage after a spike. This allows us to derive a complete expression for the dynamic gain of a resonator neuron model in terms of a cascade of filters on the input. We find six distinct response types and use them to fully characterize the routes to resonance across all values of the relevant timescales. We find that resonance arises primarily due to slow adaptation with an intrinsic frequency acting to sharpen and adjust the location of the resonant peak. We determine the parameter regions for the existence of an intrinsic frequency and for subthreshold and spiking resonance, finding all possible intersections of the three. The expressions and analysis presented here provide an account of how intrinsic neuron dynamics shape dynamic population response properties and can facilitate the construction of an exact theory of correlations and stability of population activity in networks containing populations of resonator neurons. PMID:26720924

  12. Forced and intrinsic variability in the response to increased wind stress of an idealized Southern Ocean

    NASA Astrophysics Data System (ADS)

    Wilson, Chris; Hughes, Chris W.; Blundell, Jeffrey R.

    2015-01-01

    use ensemble runs of a three layer, quasi-geostrophic idealized Southern Ocean model to explore the roles of forced and intrinsic variability in response to a linear increase of wind stress imposed over a 30 year period. We find no increase of eastward circumpolar volume transport in response to the increased wind stress. A large part of the resulting time series can be explained by a response in which the eddy kinetic energy is linearly proportional to the wind stress with a possible time lag, but no statistically significant lag is found. However, this simple relationship is not the whole story: several intrinsic time scales also influence the response. We find an e-folding time scale for growth of small perturbations of 1-2 weeks. The energy budget for intrinsic variability at periods shorter than a year is dominated by exchange between kinetic and potential energy. At longer time scales, we find an intrinsic mode with period in the region of 15 years, which is dominated by changes in potential energy and frictional dissipation in a manner consistent with that seen by Hogg and Blundell (2006). A similar mode influences the response to changing wind stress. This influence, robust to perturbations, is different from the supposed linear relationship between wind stress and eddy kinetic energy, and persists for 5-10 years in this model, suggestive of a forced oscillatory mode with period of around 15 years. If present in the real ocean, such a mode would imply a degree of predictability of Southern Ocean dynamics on multiyear time scales.

  13. Population response characteristics of intrinsic signals in the cat somatosensory cortex following canine mechanical stimulation.

    PubMed

    Tao, Jianxiang; Wang, Jian; Li, Zhong; Meng, Jianjun; Yu, Hongbo

    2016-08-01

    Intrinsic signal optical imaging has been widely used to measure functional maps in various sensory cortices due to better spatial resolution and sensitivity for detecting cortical neuroplasticity. However, application of this technique in dentistry has not been reported. In this study, intrinsic signal optical imaging was used to investigate mechanically driven responses in the cat somatosensory cortex, when punctate mechanical stimuli were applied to maxillary canines. The global signal and its spatial organization pattern were obtained. Global signal strength gradually increased with stimulus strength. There was no significant difference in response strength between contralateral and ipsilateral mechanical stimulation. A slightly greater response was recorded in the sigmoidal gyrus than in the coronal gyrus. The cat somatosensory cortex activated by sensory inputs from mechanical stimulation of canines lacks both topographical and functional organization. It is not organized into columns that represent sensory input from each tooth or direction of stimulation. These results demonstrate that intrinsic signal optical imaging is a valid tool for investigating neural responses and neuroplasticity in the somatosensory cortex that represents teeth. PMID:27163378

  14. Intrinsic slow charge response in the perovskite solar cells: Electron and ion transport

    SciTech Connect

    Shi, Jiangjian; Xu, Xin; Zhang, Huiyin; Luo, Yanhong; Li, Dongmei; Meng, Qingbo

    2015-10-19

    The intrinsic charge response and hysteresis characteristic in the perovskite solar cell has been investigated by an electrically modulated transient photocurrent technology. An ultraslow charge response process in the timescale of seconds is observed, which can be well explained by the ion migration in the perovskite CH{sub 3}NH{sub 3}PbI{sub 3} film driven by multiple electric fields derived from the heterojunction depletion charge, the external modulation, and the accumulated ion charge. Furthermore, theoretical calculation of charge transport reveals that the hysteresis behavior is also significantly influenced by the interfacial charge extraction velocity and the carrier transport properties inside the cell.

  15. Inactivating ion channels augment robustness of subthreshold intrinsic response dynamics to parametric variability in hippocampal model neurons

    PubMed Central

    Rathour, Rahul Kumar; Narayanan, Rishikesh

    2012-01-01

    Voltage-gated ion channels play a critical role in regulating neuronal intrinsic response dynamics (IRD). Here, we computationally analysed the roles of the two inactivating subthreshold conductances (A and T), individually and in various combinations with the non-inactivating h conductance, in regulating several physiological IRD measurements in the theta frequency range. We found that the independent presence of a T conductance, unlike that of an h conductance, was unable to sustain an inductive phase lead in the theta frequency range, despite its ability to mediate theta frequency resonance. The A conductance, on the other hand, when expressed independently, acted in a manner similar to a leak conductance with reference to most IRD measurements. Next, analysing the impact of pair-wise coexpression of these channels, we found that the coexpression of the h and T conductances augmented the range of parameters over which they sustained resonance and inductive phase lead. Additionally, coexpression of the A conductance with the h or the T conductance elicited changes in IRD measurements that were similar to those obtained with the expression of a leak conductance with a resonating conductance. Finally, to understand the global sensitivity of IRD measurements to all parameters associated with models expressing all three channels, we generated 100,000 neuronal models, each built with a unique set of parametric values. We categorized valid models among these by matching their IRD measurements with experimental counterparts, and found that functionally similar models could be achieved even when underlying parameters displayed tremendous variability and exhibited weak pair-wise correlations. Our results suggest that the three prominent subthreshold conductances contribute differently to intrinsic excitability and to phase coding. We postulate that the differential expression and activity-dependent plasticity of these conductances contribute to robustness of subthreshold

  16. Caulobacter crescentus intrinsic dimorphism provides a prompt bimodal response to copper stress.

    PubMed

    Lawarée, Emeline; Gillet, Sébastien; Louis, Gwennaëlle; Tilquin, Françoise; Le Blastier, Sophie; Cambier, Pierre; Matroule, Jean-Yves

    2016-01-01

    Stress response to fluctuating environments often implies a time-consuming reprogramming of gene expression. In bacteria, the so-called bet hedging strategy, which promotes phenotypic stochasticity within a cell population, is the only fast stress response described so far(1). Here, we show that Caulobacter crescentus asymmetrical cell division allows an immediate bimodal response to a toxic metals-rich environment by allocating specific defence strategies to morphologically and functionally distinct siblings. In this context, a motile swarmer cell favours negative chemotaxis to flee from a copper source, whereas a sessile stalked sibling engages a ready-to-use PcoAB copper homeostasis system, providing evidence of a prompt stress response through intrinsic bacterial dimorphism. PMID:27562256

  17. Interdiffusion and intrinsic diffusion in the NiAl /delta/ phase of the Al-Ni system

    NASA Technical Reports Server (NTRS)

    Shankar, S.; Seigle, L. L.

    1978-01-01

    Interdiffusion coefficients at 950 to 1150 C and the ratio of intrinsic diffusion coefficients at 1100 C were measured as functions of composition in the NiAl (delta) phase of the Al-Ni system, using a vapor-solid technique. Diffusivity values were also obtained for the Ni3Al (epsilon) and Ni (Al) solid solution (zeta) phases from 950 to 1150 C. The interdiffusion coefficient in NiAl (delta) varies several orders of magnitude over the delta phase field with a deep minimum in the diffusivity-composition curve at 48 to 49 at% Al. The ratio of intrinsic diffusion coefficients DNi/DAl, in the delta phase also varies with composition from a value of 3 to 3.5 below 50 at% Al to 0.1 or less above 50 at% Al.

  18. Intrinsic defects in B cell response to seasonal influenza vaccination in elderly humans

    PubMed Central

    Frasca, Daniela; Diaz, Alain; Romero, Maria; Landin, Ana Marie; Phillips, Mitch; Lechner, Suzanne C.; Ryan, John G.; Blomberg, Bonnie B.

    2010-01-01

    We have evaluated the serum response to seasonal influenza vaccination in subjects of different ages and associated this with the specific B cell response to the vaccine in vitro. Although the serum response has previously been shown to decrease with age, this has largely been associated to decreased T cell functions. Our results show that in response to the vaccine, the specific response of B cells in vitro, as measured by AID (activation-induced cytidine deaminase), the in vivo serum HI (hemagglutination inhibition) response, and the in vivo generation of switch memory B cells are decreased with age, as evaluated in the same subjects. This is the first report to demonstrate that intrinsic B cell defects with age contribute to reduced antibody responses to the influenza vaccine. The level of AID in response to CpG before vaccination can also predict the robustness of the vaccine response. These results could contribute to developing more effective vaccines to protect the elderly as well as identifying those most at risk. PMID:20974306

  19. Epithelial-intrinsic IKKα expression regulates group 3 innate lymphoid cell responses and antibacterial immunity

    PubMed Central

    Giacomin, Paul R.; Moy, Ryan H.; Noti, Mario; Osborne, Lisa C.; Siracusa, Mark C.; Alenghat, Theresa; Liu, Bigang; McCorkell, Kelly A.; Troy, Amy E.; Rak, Gregory D.; Hu, Yinling; May, Michael J.; Ma, Hak-Ling; Fouser, Lynette A.; Sonnenberg, Gregory F.

    2015-01-01

    Innate lymphoid cells (ILCs) are critical for maintaining epithelial barrier integrity at mucosal surfaces; however, the tissue-specific factors that regulate ILC responses remain poorly characterized. Using mice with intestinal epithelial cell (IEC)–specific deletions in either inhibitor of κB kinase (IKK)α or IKKβ, two critical regulators of NFκB activation, we demonstrate that IEC-intrinsic IKKα expression selectively regulates group 3 ILC (ILC3)–dependent antibacterial immunity in the intestine. Although IKKβΔIEC mice efficiently controlled Citrobacter rodentium infection, IKKαΔIEC mice exhibited severe intestinal inflammation, increased bacterial dissemination to peripheral organs, and increased host mortality. Consistent with weakened innate immunity to C. rodentium, IKKαΔIEC mice displayed impaired IL-22 production by RORγt+ ILC3s, and therapeutic delivery of rIL-22 or transfer of sort-purified IL-22–competent ILCs from control mice could protect IKKαΔIEC mice from C. rodentium–induced morbidity. Defective ILC3 responses in IKKαΔIEC mice were associated with overproduction of thymic stromal lymphopoietin (TSLP) by IECs, which negatively regulated IL-22 production by ILC3s and impaired innate immunity to C. rodentium. IEC-intrinsic IKKα expression was similarly critical for regulation of intestinal inflammation after chemically induced intestinal damage and colitis. Collectively, these data identify a previously unrecognized role for epithelial cell–intrinsic IKKα expression and TSLP in regulating ILC3 responses required to maintain intestinal barrier immunity. PMID:26371187

  20. Simultaneous imaging of intrinsic optical signals and cerebral vessel responses during cortical spreading depression in rats

    NASA Astrophysics Data System (ADS)

    Li, Pengcheng; Chen, Shangbin; Luo, Weihua; Luo, Qingming

    2003-12-01

    Cortical spreading depression (CSD) is an important disease model for migraine and cerebral ischemia. We investigated the spatio-temporal characteristics of the intrinsic optical signals (IOS) at 570 nm and the cerebral blood vessel responses during CSD simultaneously by optical reflectance imaging in vivo. The CSD were induced by pinprick in 10 α-chloralose/urethane anesthetized Sprague-Dawley rats. A four-phasic IOS response was observed at pial arteries and parenchymal sites in all experimental animals and an initial slight pial arteries dilation (21.5%+/-13.6%) and constriction (-4.2%+/-3.5%) precedes the dramatic dilation (69.2%+/-26.1%) of pial arterioles was recorded. Our experimental results show a high correlation (r = 0.89+/-0.025) between the IOS response and the diameter changes of the cerebral blood vessels during CSD in rats.

  1. Increase of Phase Retrapping Effects in the Switching Rate from the Finite Voltage State of the Underdamped Intrinsic Josephson Junctions

    NASA Astrophysics Data System (ADS)

    Kitano, Haruhisa; Takahashi, Yusaku; Kakehi, Daiki; Yamaguchi, Hikaru; Koizumi, Shin-ichiro; Ayukawa, Shin-ya

    2016-05-01

    We report a detailed study of the phase switching rate from the first to the fourth switch for a small stack of Bi2Sr2CaCu2Oy intrinsic Josephson junctions (IJJs). Experimental results were analyzed by using the conventional single-junction model including the thermally-activated phase escape and the multiple phase retrapping. It is shown that the phase retrapping effects are more prominent for higher order switches, even for the underdamped IJJs showing a large hysteresis in the current–voltage characteristics. This clearly suggests that the tilted washboard potential representing the phase switch from the finite voltage state in IJJs can be influenced by a rapid oscillation generated in a phase-switched junction.

  2. Theanine prevents doxorubicin-induced acute hepatotoxicity by reducing intrinsic apoptotic response.

    PubMed

    Nagai, Katsuhito; Oda, Ayano; Konishi, Hiroki

    2015-04-01

    Doxorubicin (DOX) is widely used as an antitumor agent with topoisomerase II inhibiting activity; however, its dosage and duration of administration have been strictly limited due to dose-related organ damage. The present study investigated whether theanine, an amino acid found in green tea leaves, could reduce DOX-induced acute hepatotoxicity and the apoptotic response in mice. Activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum, biomarkers of hepatic impairment, were markedly increased after the administration of 20 mg/kg DOX, whereas the degree of these elevations was significantly attenuated by 10 mg/kg theanine, which was consistent with histological hepatic images assessed by microscopic examination. The hepatic expression of Bax and Fas, representative intrinsic and extrinsic apoptotic molecules, respectively, was significantly increased by dosing with DOX. However, the elevation in the hepatic expression of Bax, but not Fas, was suppressed to control levels by theanine. The formation of cleaved caspase-3 protein in the group given DOX with theanine was significantly lower than that in the group treated with DOX alone. These results suggest that theanine can protect against acute hepatic damage induced by DOX, which is attributed to the suppression of intrinsic caspase-3-dependent apoptotic signaling. PMID:25680506

  3. Measuring Students' Perceptions of Personal and Social Responsibility and the Relationship to Intrinsic Motivation in Urban Physical Education

    ERIC Educational Resources Information Center

    Li, Weidong; Wright, Paul M.; Rukavina, Paul Bernard; Pickering, Molly

    2008-01-01

    The purpose of the current study was to test the validity and reliability of a two-factor model of the Personal and Social Responsibility Questionnaire (PSRQ) and examine the relationships between perceptions of personal and social responsibility and intrinsic motivation in physical education. Participants were 253 middle school students who…

  4. Berry phases and the intrinsic thermal Hall effect in high-temperature cuprate superconductors.

    PubMed

    Cvetkovic, Vladimir; Vafek, Oskar

    2015-01-01

    Bogolyubov quasiparticles move in a practically uniform magnetic field in the vortex state of high-temperature cuprate superconductors. When set in motion by an externally applied heat current, the quasiparticles' trajectories may bend, causing a temperature gradient perpendicular to the heat current and the applied magnetic field, resulting in the thermal Hall effect. Here we relate this effect to the Berry curvature of quasiparticle magnetic sub-bands, and calculate the dependence of the intrinsic thermal Hall conductivity on superconductor's temperature, magnetic field and the amplitude of the d-wave pairing. The intrinsic contribution to thermal Hall conductivity displays a rapid onset with increasing temperature, which compares favourably with existing experiments at high magnetic field on the highest purity samples. Because such temperature onset is related to the pairing amplitude, our finding may help to settle a much-debated question of the bulk value of the pairing strength in cuprate superconductors in magnetic field. PMID:25758469

  5. Macroscopic quantum tunneling and phase diffusion in a La2-xSrxCuO4 intrinsic Josephson junction stack

    NASA Astrophysics Data System (ADS)

    Kubo, Yuimaru; Sboychakov, A. O.; Nori, Franco; Takahide, Y.; Ueda, S.; Tanaka, I.; Islam, A. T. M. N.; Takano, Y.

    2012-10-01

    We performed measurements of switching current distribution in a submicrometer La2-xSrxCuO4 (LSCO) intrinsic Josephson junction (IJJ) stack in a wide temperature range. The escape rate saturates below approximately 2 K, indicating that the escape event is dominated by a macroscopic quantum tunneling (MQT) process with a crossover temperature T*≈2K. We applied the theory of MQT for IJJ stacks, taking into account dissipation and the phase retrapping effect in the LSCO IJJ stack. The theory is in good agreement with the experiment both in the MQT and in the thermal activation regimes.

  6. Resonant phase escape in Bi2Sr2CaCu2O8+δ surface intrinsic Josephson junctions

    NASA Astrophysics Data System (ADS)

    Yu, H. F.; Zhu, X. B.; Ren, J. K.; Peng, Z. H.; Cui, D. J.; Deng, H.; Cao, W. H.; Tian, Ye; Chen, G. H.; Zheng, D. N.; Jing, X. N.; Lu, Li; Zhao, S. P.

    2013-09-01

    We present a study of phase escape in surface Bi2Sr2CaCu2O8+δ intrinsic Josephson junctions in the presence of microwave radiation. The measured switching current distributions display clear double-peak structures in the microwave field, which result from the single- and two-photon resonant escape processes accompanied by microwave-induced potential barrier suppression. We show that these results can be well explained by a quantum-mechanical model proposed by Fistul et al (2003 Phys. Rev. B 68 060504), from which the power and frequency dependences of the switching current distributions can be reproduced.

  7. Microsecond Molecular Dynamics Simulations of Intrinsically Disordered Proteins Involved in the Oxidative Stress Response

    PubMed Central

    Cino, Elio A.; Wong-ekkabut, Jirasak; Karttunen, Mikko; Choy, Wing-Yiu

    2011-01-01

    Intrinsically disordered proteins (IDPs) are abundant in cells and have central roles in protein-protein interaction networks. Interactions between the IDP Prothymosin alpha (ProTα) and the Neh2 domain of Nuclear factor erythroid 2-related factor 2 (Nrf2), with a common binding partner, Kelch-like ECH-associated protein 1(Keap1), are essential for regulating cellular response to oxidative stress. Misregulation of this pathway can lead to neurodegenerative diseases, premature aging and cancer. In order to understand the mechanisms these two disordered proteins employ to bind to Keap1, we performed extensive 0.5–1.0 microsecond atomistic molecular dynamics (MD) simulations and isothermal titration calorimetry experiments to investigate the structure/dynamics of free-state ProTα and Neh2 and their thermodynamics of bindings. The results show that in their free states, both ProTα and Neh2 have propensities to form bound-state-like β-turn structures but to different extents. We also found that, for both proteins, residues outside the Keap1-binding motifs may play important roles in stabilizing the bound-state-like structures. Based on our findings, we propose that the binding of disordered ProTα and Neh2 to Keap1 occurs synergistically via preformed structural elements (PSEs) and coupled folding and binding, with a heavy bias towards PSEs, particularly for Neh2. Our results provide insights into the molecular mechanisms Neh2 and ProTα bind to Keap1, information that is useful for developing therapeutics to enhance the oxidative stress response. PMID:22125611

  8. Identification of intrinsic deep level defects responsible for electret behavior in TlGaSe2 layered semiconductor

    NASA Astrophysics Data System (ADS)

    Seyidov, MirHasan Yu.; Mikailzade, Faik A.; Uzun, Talip; Odrinsky, Andrei P.; Yakar, Emin; Aliyeva, Vafa B.; Babayev, Sardar S.; Mammadov, Tofig G.

    2016-02-01

    Unusual behavior of pyroelectric current signal polarity near the Curie point (Tc) was observed for TlGaSe2 a ferroelectric-semiconductor. It has been revealed that the polarity of the spontaneous polarization near Tc depends on the sample poling prehistory. In particular, applying an external electric field only in the temperature range of the paraelectric state during cooling regime in darkness brought to the depolarization current at Tc with the sign opposite to the external field polarity. Otherwise, if the sample was poled in the temperature interval of the incommensurate phase, pyroelectric current exhibits a peak at Tc with the polarity that is the same as for the external poling electric field. These observations indicate that internal electric field is present in the bulk and near-surface layer regions of the electrically poled single crystal TlGaSe2. Possible mechanisms and origins responsible for the internal electric fields in TlGaSe2 are discussed. It is shown that the formation of internal electric fields in TlGaSe2 is due to charging of intrinsic native defects during the poling process. Characteristics of electrically active intrinsic defects in TlGaSe2 were investigated by using of Photo-Induced Current Transient Spectroscopy (PICTS) technique. Six deep defect levels in the band gap of TlGaSe2 were determined, which were localized both in the bulk and on the surface of the sample and could be electrically charged. The correlation between polarization effects and PICTS results has been established. It was shown that native deep defects (A3-A6) localized in the bulk of crystal are responsible for hetero-charge formation and negative sign of the pyroelectric current peak observed around the Curie temperature after poling the sample in the temperature intervals well above Tc. It was also shown that the positive sign pyrocurrent observed near the Curie point is attributed to the homo-charge formed by native A2-trapping centers which are localized near

  9. Surface wave tomography with USArray based on phase front tracking and amplitude mapping: isotropic, anisotropic, and intrinsic attenuation structures

    NASA Astrophysics Data System (ADS)

    Lin, F.; Ritzwoller, M. H.

    2011-12-01

    The deployment of the EarthScope/USArray Transportable Array has promoted new and better ways to utilize the dense array configuration and to resolve higher resolution crustal and upper mantle structures beneath the US. Here, we present a local inversion method for surface wave that utilizes the USArray first to determine the surface wave wavefield empirically and then to directly measure the surface wave propagation characteristics such as isotropic velocity, azimuthal anisotropy, and intrinsic attenuation by solving the 2D Helmholtz wave equation. The method starts with single event analysis, where for each period and earthquake all measurements across the array are aggregated to determine maps of phase travel time and amplitude on a fine spatial grid, which essentially describes the surface wave wavefield. The solution of the 2D wave equation contains real and imaginary parts, which are relevant to velocity and attenuation measurements, respectively. For the real part, directionally dependent phase velocities at each location are estimated from the gradient of phase travel time along with the Laplacian of amplitude. For the imaginary part, on the other hand, intrinsic attenuation at each location is estimated from the dot product of the gradients of phase travel time and amplitude along with the Laplacian of phase travel time. In both cases, the terms that contain the gradient operator are directly related to traditional ray theoretic approaches (e.g., eikonal equation for velocity measurement) whereas the terms involving the Laplacian operator provide corrections for off-ray sensitivity. In principle, by applying the correction terms, finite frequency effects such as wave interference, wavefront healing, and backward scattering are accounted for in phase velocity measurements and focus/defocusing is accounted for in attenuation measurements. We apply the method to Rayleigh wave measurements between 30 and 100 sec period from more than 700 earthquakes and all

  10. Intrinsic increase in lymphangion muscle contractility in response to elevated afterload

    PubMed Central

    Scallan, Joshua P.; Wolpers, John H.; Muthuchamy, Mariappan; Gashev, Anatoliy A.; Zawieja, David C.

    2012-01-01

    Collecting lymphatic vessels share functional and biochemical characteristics with cardiac muscle; thus, we hypothesized that the lymphatic vessel pump would exhibit behavior analogous to homeometric regulation of the cardiac pump in its adaptation to elevated afterload, i.e., an increase in contractility. Single lymphangions containing two valves were isolated from the rat mesenteric microcirculation, cannulated, and pressurized for in vitro study. Pressures at either end of the lymphangion [input pressure (Pin), preload; output pressure (Pout), afterload] were set by a servo controller. Intralymphangion pressure (PL) was measured using a servo-null micropipette while internal diameter and valve positions were monitored using video methods. The responses to step- and ramp-wise increases in Pout (at low, constant Pin) were determined. PL and diameter data recorded during single contraction cycles were used to generate pressure-volume (P-V) relationships for the subsequent analysis of lymphangion pump behavior. Ramp-wise Pout elevation led to progressive vessel constriction, a rise in end-systolic diameter, and an increase in contraction frequency. Step-wise Pout elevation produced initial vessel distention followed by time-dependent declines in end-systolic and end-diastolic diameters. Significantly, a 30% leftward shift in the end-systolic P-V relationship accompanied an 84% increase in dP/dt after a step increase in Pout, consistent with an increase in contractility. Calculations of stroke work from the P-V loop area revealed that robust pumps produced net positive work to expel fluid throughout the entire afterload range, whereas weaker pumps exhibited progressively more negative work as gradual afterload elevation led to pump failure. We conclude that lymphatic muscle adapts to output pressure elevation with an intrinsic increase in contractility and that this compensatory mechanism facilitates the maintenance of lymph pump output in the face of edemagenic and

  11. Theoretical characterization on intrinsic ferrimagnetic phase in nanoscale laminated Cr2GeC

    NASA Astrophysics Data System (ADS)

    Li, N.; Dharmawardhana, C. C.; Yao, K. L.; Ching, W. Y.

    2013-11-01

    The structural, electronic and magnetic properties of the hexagonal nanolaminated layered MAX phases compound Cr2GeC are investigated using the full-potential linearized augmented-plane-waves (FPLAPW) method within the generalized gradient approximation (GGA) and GGA+U calculations. The results indicate Cr2GeC has a sizable moment of 1.667 μB revealing the existence of a ferrimagnetic ground state in a MAX phase compound. This surprising new result will lead to the possibility of applying the layered magnetic MAX phase compounds in electronics and spintronics areas.

  12. In-phase electrodynamics and terahertz wave emission in extended intrinsic Josephson junctions

    NASA Astrophysics Data System (ADS)

    Koyama, Tomio; Matsumoto, Hideki; Machida, Masahiko; Kadowaki, Kazuo

    2009-03-01

    Strong emission of subterahertz electromagnetic (EM) waves has been observed recently in the high Tc superconductor Bi2Sr2CaCu2O8 intrinsic Josephson junctions (IJJ’s). We investigate numerically the dynamics of the EM fields both inside and outside the IJJ’s emitting terahertz EM waves under a constant bias current, using two-dimensional models composed of IJJ’s and the space surrounding them: (1) xy model and (2) xz model. In the xy model we investigate the EM modes excited in the rectangular junctions. In the voltage state the Josephson oscillation generates the oscillating EM field having nodes inside the junctions. The number of nodes depends on the DC voltage appearing in the junctions, and their direction is parallel to the shorter side of the junctions. The EM field shows a complex distribution pattern in the near field region. In the region far from the junctions we have only the expanding EM wave oscillating with the Josephson frequency. In the xz model we study the EM waves emitted in the xz plane from the junctions covered with normal electrodes. It is shown that the power of the emitted EM waves has distribution similar to that in the dipole emission in the system where electrodes of the same size are attached on top and bottom junctions. In the asymmetric system where the lower electrode is larger than the upper one the power distribution of emitted EM wave deviates from that in the dipole emission.

  13. Intrinsic optical signal imaging of glucose-stimulated physiological responses in the insulin secreting INS-1 β-cell line

    NASA Astrophysics Data System (ADS)

    Li, Yi-Chao; Cui, Wan-Xing; Wang, Xu-Jing; Amthor, Franklin; Yao, Xin-Cheng

    2011-03-01

    Intrinsic optical signal (IOS) imaging has been established for noninvasive monitoring of stimulus-evoked physiological responses in the retina and other neural tissues. Recently, we extended the IOS imaging technology for functional evaluation of insulin secreting INS-1 cells. INS-1 cells provide a popular model for investigating β-cell dysfunction and diabetes. Our experiments indicate that IOS imaging allows simultaneous monitoring of glucose-stimulated physiological responses in multiple cells with high spatial (sub-cellular) and temporal (sub-second) resolution. Rapid image sequences reveal transient optical responses that have time courses comparable to glucose-evoked β-cell electrical activities.

  14. Intrinsic Charge Transport across Phase Transitions in Hybrid Organo-Inorganic Perovskites.

    PubMed

    Yi, Hee Taek; Wu, Xiaoxi; Zhu, Xiaoyang; Podzorov, Vitaly

    2016-08-01

    Hall effect measurements in CH3 NH3 PbBr3 single crystals reveal that the charge-carrier mobility follows an inverse-temperature power-law dependence, μ ∝ T(-) (γ) , with the power exponent γ = 1.4 ± 0.1 in the cubic phase, indicating an acoustic-phonon-dominated carrier scattering, and γ = 0.5 ± 0.1 in the tetragonal phase, suggesting another dominant mechanism, such as a piezoelectric or space-charge scattering. PMID:27185304

  15. The Pervasive Negative Effects of Rewards on Intrinsic Motivation: Response to Cameron (2001).

    ERIC Educational Resources Information Center

    Deci, Edward L.; Ryan, Richard M.; Koestner, Richard

    2001-01-01

    Replies to commentary by J. Cameron asserting that the negative results of extrinsic reward on intrinsic motivation are limited and avoidable. Suggests that the most recent meta analysis by Cameron and others shares methodological weaknesses with an earlier analysis, lacking ecological validity. (SLD)

  16. Heterodyne coherent anti-Stokes Raman scattering by the phase control of its intrinsic background

    SciTech Connect

    Wang Xi; Wang Kai; Welch, George R.; Sokolov, Alexei V.

    2011-08-15

    We demonstrate the use of femtosecond laser pulse shaping for precise control of the interference between the coherent anti-Stokes Raman scattering (CARS) signal and the coherent nonresonant background generated within the same sample volume. Our technique is similar to heterodyne detection with the coherent background playing the role of the local oscillator field. In our experiment, we first apply two ultrashort (near-transform-limited) femtosecond pump and Stokes laser pulses to excite coherent molecular oscillations within a sample. After a short and controllable delay, we then apply a laser pulse that scatters off of these oscillations to produce the CARS signal. By making fine adjustments to the probe field spectral profile, we vary the relative phase between the Raman-resonant signal and the nonresonant background, and we observe a varying spectral interference pattern. These controlled variations of the measured pattern reveal the phase information within the Raman spectrum.

  17. Heterodyne coherent anti-Stokes Raman scattering by the phase control of its intrinsic background

    NASA Astrophysics Data System (ADS)

    Wang, Xi; Wang, Kai; Welch, George R.; Sokolov, Alexei V.

    2011-08-01

    We demonstrate the use of femtosecond laser pulse shaping for precise control of the interference between the coherent anti-Stokes Raman scattering (CARS) signal and the coherent nonresonant background generated within the same sample volume. Our technique is similar to heterodyne detection with the coherent background playing the role of the local oscillator field. In our experiment, we first apply two ultrashort (near-transform-limited) femtosecond pump and Stokes laser pulses to excite coherent molecular oscillations within a sample. After a short and controllable delay, we then apply a laser pulse that scatters off of these oscillations to produce the CARS signal. By making fine adjustments to the probe field spectral profile, we vary the relative phase between the Raman-resonant signal and the nonresonant background, and we observe a varying spectral interference pattern. These controlled variations of the measured pattern reveal the phase information within the Raman spectrum.

  18. All-optical quantum random bit generation from intrinsically binary phase of parametric oscillators.

    PubMed

    Marandi, Alireza; Leindecker, Nick C; Vodopyanov, Konstantin L; Byer, Robert L

    2012-08-13

    We demonstrate a novel all-optical quantum random number generator (RNG) based on above-threshold binary phase state selection in a degenerate optical parametric oscillator (OPO). Photodetection is not a part of the random process, and no post processing is required for the generated bit sequence. We show that the outcome is statistically random with 99% confidence, and verify that the randomness is due to the phase of initiating photons generated through spontaneous parametric down conversion of the pump, with negligible contribution of classical noise sources. With the use of micro- and nanoscale OPO resonators, this technique offers a promise for simple, robust, and high-speed on-chip all-optical quantum RNGs. PMID:23038574

  19. Interdiffusion in the Mg-Al system and Intrinsic Diffusion in (Al3Mg2) Phase

    SciTech Connect

    Brennan, Sarah; Bermudez, Katrina; Kulkarni, Nagraj S; Sohn, Yong Ho

    2011-01-01

    Increasing use and development of lightweight Mg-alloys have led to the desire for more fundamental research in and understanding of Mg-based systems. As a strengthening component, Al is one of the most important and common alloying elements for Mg-alloys. In this study, solid-to-solid diffusion couple techniques were employed to examine the interdiffusion between pure Mg and Al. Diffusion anneals were carried out at 300 , 350 , and 400 C for 720, 360, and 240 hours, respectively. Optical and scanning electron microscopies (SEM) were employed to observe the formation of the intermetallics -Al12Mg17 and -Al3Mg2, but not -phase. Concentration profiles were determined using X-ray energy dispersive spectroscopy (XEDS). The growth constants and activation energies were determined for each intermetallic phase.

  20. Intrinsic magnetic properties of single-phase Mn1+xGa (0 < x < 1) alloys

    PubMed Central

    Lu, Q. M.; Yue, M.; Zhang, H. G.; Wang, M. L.; Yu, F.; Huang, Q. Z.; Ryan, D. H.; Altounian, Z.

    2015-01-01

    Magnetization measurements have been carried out on a series of carefully prepared single-phase Mn1 + xGa (0 < x < 1) alloys. The saturation magnetization Ms, measured at 5 K, has a value of 92.0 emu/g for x = 0.15. This is the highest value reported in these alloys and is close to the calculated value of 116 emu/g for the stoichiometric compound (x = 0). Ms decreases gradually with x and has a value of 60.7 emu/g for x = 0.86. This behavior is consistent with the extra Mn atoms occupying Ga sites and coupling antiferromagnetically with the rest of the Mn atoms. The intrinsic magnetic properties of the Mn-Ga alloys indicate their great potential as novel, rare-earth free permanent magnetic materials. PMID:26597458

  1. Voltage sensing systems and methods for passive compensation of temperature related intrinsic phase shift

    DOEpatents

    Davidson, James R.; Lassahn, Gordon D.

    2001-01-01

    A small sized electro-optic voltage sensor capable of accurate measurement of high levels of voltages without contact with a conductor or voltage source is provided. When placed in the presence of an electric field, the sensor receives an input beam of electromagnetic radiation into the sensor. A polarization beam displacer serves as a filter to separate the input beam into two beams with orthogonal linear polarizations. The beam displacer is oriented in such a way as to rotate the linearly polarized beams such that they enter a Pockels crystal at a preferred angle of 45 degrees. The beam displacer is therefore capable of causing a linearly polarized beam to impinge a crystal at a desired angle independent of temperature. The Pockels electro-optic effect induces a differential phase shift on the major and minor axes of the input beam as it travels through the Pockels crystal, which causes the input beam to be elliptically polarized. A reflecting prism redirects the beam back through the crystal and the beam displacer. On the return path, the polarization beam displacer separates the elliptically polarized beam into two output beams of orthogonal linear polarization representing the major and minor axes. In crystals that introduce a phase differential attributable to temperature, a compensating crystal is provided to cancel the effect of temperature on the phase differential of the input beam. The system may include a detector for converting the output beams into electrical signals, and a signal processor for determining the voltage based on an analysis of the output beams. The output beams are amplitude modulated by the frequency of the electric field and the amplitude of the output beams is proportional to the magnitude of the electric field, which is related to the voltage being measured.

  2. How intrinsic sympathomimetic activity modulates the haemodynamic responses to β-adrenoceptor antagonists

    PubMed Central

    Veld, A. J. Man in 'T; Schalekamp, M. A. D. H.

    1982-01-01

    1 A survey has been made of the literature on acute and long-term haemodynamic effects of ten different β-adrenoceptor antagonists. The β-adrenoceptor blockers are: pindolol, practolol, alprenolol, oxprenolol, acebutolol, penbutolol, metoprolol, atenolol, propranolol and timolol. The total numbers of patients included in this review are 396 patients in 41 acute studies and 410 patients in 36 long-term studies. 2 The effects of β-adrenoceptor blockers on the concentrations of plasma noradrenaline have also been reviewed. Ten studies including 110 patients on non-ISA-β-adrenoceptor blockers and eight studies including 116 patients on pindolol are presented. 3 In the acute studies (i.e. 15-90 min) arterial pressure was lowered by 1-7% and in the long-term studies (i.e. 3 days-5 years) by 6-17%. 4 The degree of cardio-depression induced by the various β-adrenoceptor blockers was inversely correlated with their pharmacologically defined quantity of intrinsic sympathomimetic activity (ISA) both in acute and in long-term studies. 5 In the acute studies the increments in peripheral vascular resistance were directly correlated with the degree of cardio-depression. This suggests that a fall in arterial pressure immediately after administration of a β-adrenoceptor blocker is prevented by increased vasoconstrictor nerve activity mediated through the arterial baroreflex. 6 The compensatory response of vascular resistance to cardio-depression was similar for β1-selective and non-selective blockers, thereby indicating that extra-junctional vascular β-receptors are relatively unimportant for maintaining basal vascular tone. 7 In the long-term studies the correlation between changes in cardiac output and changes in vascular resistance was shifted to a lower level of vascular resistance. This means that the onset of blood pressure reduction during β-adrenoceptor blockade was associated with a fall in vascular resistance at any level of cardiac output. Thus vascular

  3. Maggot excretion products from the blowfly Lucilia sericata contain contact phase/intrinsic pathway-like proteases with procoagulant functions.

    PubMed

    Kahl, M; Gökçen, A; Fischer, S; Bäumer, M; Wiesner, J; Lochnit, G; Wygrecka, M; Vilcinskas, A; Preissner, K T

    2015-08-01

    For centuries, maggots have been used for the treatment of wounds by a variety of ancient cultures, as part of their traditional medicine. With increasing appearance of antimicrobial resistance and in association with diabetic ulcers, maggot therapy was revisited in the 1980s. Three mechanisms by which sterile maggots of the green bottle fly Lucilia sericata may improve healing of chronic wounds have been proposed: Biosurgical debridement, disinfecting properties, and stimulation of the wound healing process. However, the influence of maggot excretion products (MEP) on blood coagulation as part of the wound healing process has not been studied in detail. Here, we demonstrate that specific MEP-derived serine proteases from Lucilia sericata induce clotting of human plasma and whole blood, particularly by activating contact phase proteins factor XII and kininogen as well as factor IX, thereby providing kallikrein-bypassing and factor XIa-like activities, both in plasma and in isolated systems. In plasma samples deficient in contact phase proteins, MEP restored full clotting activity, whereas in plasma deficient in either factor VII, IX, X or II no effect was seen. The observed procoagulant/intrinsic pathway-like activity was mediated by (chymo-) trypsin-like proteases in total MEP, which were significantly blocked by C1-esterase inhibitor or other contact phase-specific protease inhibitors. No significant influence of MEP on platelet activation or fibrinolysis was noted. Together, MEP provides contact phase bypassing procoagulant activity and thereby induces blood clotting in the context of wound healing. Further characterisation of the active serine protease(s) may offer new perspectives for biosurgical treatment of chronic wounds. PMID:25948398

  4. Interaction between the intrinsic edge state and the helical boundary state of topological insulator phase in bilayer graphene

    NASA Astrophysics Data System (ADS)

    Lü, Xiaoling; Jiang, Liwei; Zheng, Yisong

    2016-04-01

    Graphene has intrinsic edge states localized at zigzag edge or lattice defect. Helical boundary states can also be established in such a two-dimensional carbon material at the boundary of topological insulator (TI) phase realized by the extrinsic Rashba spin-orbital coupling (SOC) in gated bilayer graphene. We theoretically investigate the interaction between these two kinds of edge (boundary) states when they coexist in a bilayer graphene. We find that this interaction gives rise to some very interesting results. In a zigzag edged nanoribbon of bilayer graphene, it is possible that the TI helical state does not localize at the TI phase boundary. Instead it moves to the nanoribbon edge even though the SOC is absent therein. In a bulk lattice of bilayer graphene embedded with two line defects, the numbers of helical state subbands at the two line defects are not equal to each other. In such a case, the backscattering lacking is still forbidden since the Kramers pairs are valley polarized.

  5. Pathobiochemical mechanisms during the acute phase response.

    PubMed

    Kleesiek, K; Greiling, H

    1984-01-01

    The acute phase response is characterised by the following sequence of principle phenomena: (1) an early local inflammatory reaction, (2) formation of inflammatory humoral factors inducing a systemic reaction, (3) stimulation of glycoprotein synthesis predominantly in the hepatocytes, and (4) an increase in the plasma concentration of acute phase proteins, when the rate of biosynthesis exceeds the degradation rate. Inflammatory mediators (lysosomal enzymes, oxygen derived radicals, prostaglandins) are mainly released during phagocytosis by granulocytes and macrophages. The signal reaching the hepatocytes is not yet clearly identified. A leukocyte endogenous mediator (LEM) released by macrophages is described. There is evidence that prostaglandins and probably proteinase alpha 2-macroglobulin complexes are also involved. The hepatic acute phase protein synthesis is modulated by hormones (insulin, cortisol, somatotropin). The biochemical events in the hepatocyte include an increase in protein synthesis and the regulatory control of the glycosylation of polypeptide precursors. The secreted glycoproteins serve variously as inhibitors or mediators of the inflammatory processes. PMID:6208159

  6. Monocytes from Irf5-/- mice have an intrinsic defect in their response to pristane-induced lupus.

    PubMed

    Yang, Lisong; Feng, Di; Bi, Xiaohui; Stone, Rivka C; Barnes, Betsy J

    2012-10-01

    The transcription factor IFN regulatory factor (IRF)5 has been identified as a human systemic lupus erythematosus (SLE) susceptibility gene by numerous joint linkage and genome-wide association studies. Although IRF5 expression is significantly elevated in primary blood cells of SLE patients, it is not yet known how IRF5 contributes to SLE pathogenesis. Recent data from mouse models of lupus indicate a critical role for IRF5 in the production of pathogenic autoantibodies and the expression of Th2 cytokines and type I IFN. In the present study, we examined the mechanisms by which loss of Irf5 protects mice from pristane-induced lupus at early time points of disease development. We demonstrate that Irf5 is required for Ly6C(hi) monocyte trafficking to the peritoneal cavity, which is thought to be one of the initial key events leading to lupus pathogenesis in this model. Chemotaxis assays using peritoneal lavage from pristane-injected Irf5(+/+) and Irf5(-/-) littermates support an intrinsic defect in Irf5(-/-) monocytes. We found the expression of chemokine receptors CXCR4 and CCR2 to be dysregulated on Irf5(-/-) monocytes and less responsive to their respective ligands, CXCL12 and CCL2. Bone marrow reconstitution experiments further supported an intrinsic defect in Irf5(-/-) monocytes because Irf5(+/+) monocytes were preferentially recruited to the peritoneal cavity in response to pristane. Taken together, these findings demonstrate an intrinsic role for IRF5 in the response of monocytes to pristane and their recruitment to the primary site of inflammation that is thought to trigger lupus onset in this experimental model of SLE. PMID:22933628

  7. Cell intrinsic role of NF-κB-inducing kinase in regulating T cell-mediated immune and autoimmune responses

    PubMed Central

    Li, Yanchuan; Wang, Hui; Zhou, Xiaofei; Xie, Xiaoping; Chen, Xiang; Jie, Zuliang; Zou, Qiang; Hu, Hongbo; Zhu, Lele; Cheng, Xuhong; Brightbill, Hans D; Wu, Lawren C.; Wang, Linfang; Sun, Shao-Cong

    2016-01-01

    NF-κB inducing kinase (NIK) is a central component of the noncanonical NF-κB signaling pathway. Although NIK has been extensively studied for its function in the regulation of lymphoid organ development and B-cell maturation, the role of NIK in regulating T cell functions remains unclear and controversial. Using T cell-conditional NIK knockout mice, we here demonstrate that although NIK is dispensable for thymocyte development, it has a cell-intrinsic role in regulating the homeostasis and function of peripheral T cells. T cell-specific NIK ablation reduced the frequency of effector/memory-like T cells and impaired T cell responses to bacterial infection. The T cell-conditional NIK knockout mice were also defective in generation of inflammatory T cells and refractory to the induction of a T cell-dependent autoimmune disease, experimental autoimmune encephalomyelitis. Our data suggest a crucial role for NIK in mediating the generation of effector T cells and their recall responses to antigens. Together, these findings establish NIK as a cell-intrinsic mediator of T cell functions in both immune and autoimmune responses. PMID:26912039

  8. Assembly in G1 phase and long-term stability are unique intrinsic features of CENP-A nucleosomes

    PubMed Central

    Bodor, Dani L.; Valente, Luis P.; Mata, João F.; Black, Ben E.; Jansen, Lars E. T.

    2013-01-01

    Centromeres are the site of kinetochore formation during mitosis. Centromere protein A (CENP-A), the centromere-specific histone H3 variant, is essential for the epigenetic maintenance of centromere position. Previously we showed that newly synthesized CENP-A is targeted to centromeres exclusively during early G1 phase and is subsequently maintained across mitotic divisions. Using SNAP-based fluorescent pulse labeling, we now demonstrate that cell cycle–restricted chromatin assembly at centromeres is unique to CENP-A nucleosomes and does not involve assembly of other H3 variants. Strikingly, stable retention is restricted to the CENP-A/H4 core of the nucleosome, which we find to outlast general chromatin across several cell divisions. We further show that cell cycle timing of CENP-A assembly is independent of centromeric DNA sequences and instead is mediated by the CENP-A targeting domain. Unexpectedly, this domain also induces stable transmission of centromeric nucleosomes, independent of the CENP-A deposition factor HJURP. This demonstrates that intrinsic properties of the CENP-A protein direct its cell cycle–restricted assembly and induces quantitative mitotic transmission of the CENP-A/H4 nucleosome core, ensuring long-term stability and epigenetic maintenance of centromere position. PMID:23363600

  9. Green synthesis of bacterial mediated anti-proliferative gold nanoparticles: inducing mitotic arrest (G2/M phase) and apoptosis (intrinsic pathway)

    NASA Astrophysics Data System (ADS)

    Ganesh Kumar, C.; Poornachandra, Y.; Chandrasekhar, Cheemalamarri

    2015-11-01

    The physiochemical and biological properties of microbial derived gold nanoparticles have potential applications in various biomedical domains as well as in cancer therapy. We have fabricated anti-proliferative bacterial mediated gold nanoparticles (b-Au NPs) using a culture supernatant of Streptomyces clavuligerus and later characterized them by UV-visible, TEM, DLS, XRD and FT-IR spectroscopic techniques. The capping agent responsible for the nanoparticle formation was characterized based on SDS-PAGE and MALDI-TOF-MS analyses. They were tested for anticancer activity in A549, HeLa and DU145 cell lines. The biocompatibility and non-toxic nature of the nanoparticles were tested on normal human lung cell line (MRC-5). The b-Au NPs induced the cell cycle arrest in G2/M phase and also inhibited the microtubule assembly in DU145 cells. Mechanistic studies, such as ROS, MMP, Cyt-c, GSH, caspases 9, 8 and 3 activation and the Annexin V-FITC staining, along with the above parameters tested provided sufficient evidence that the b-Au NPs induced apoptosis through the intrinsic pathway. The results supported the use of b-Au NPs for future therapeutic application in cancer therapy and other biomedical applications.The physiochemical and biological properties of microbial derived gold nanoparticles have potential applications in various biomedical domains as well as in cancer therapy. We have fabricated anti-proliferative bacterial mediated gold nanoparticles (b-Au NPs) using a culture supernatant of Streptomyces clavuligerus and later characterized them by UV-visible, TEM, DLS, XRD and FT-IR spectroscopic techniques. The capping agent responsible for the nanoparticle formation was characterized based on SDS-PAGE and MALDI-TOF-MS analyses. They were tested for anticancer activity in A549, HeLa and DU145 cell lines. The biocompatibility and non-toxic nature of the nanoparticles were tested on normal human lung cell line (MRC-5). The b-Au NPs induced the cell cycle arrest in G2

  10. The acute phase response in panic disorder.

    PubMed

    Herrán, Andrés; Sierra-Biddle, Deirdre; García-Unzueta, Maria Teresa; Puente, Jesús; Vázquez-Barquero, José Luis; Antonio Amado, José

    2005-12-01

    An acute-phase response (APR), manifested as an increase of acute-phase proteins has been shown in major depression. Panic disorder (PD) may share some aetiopathogenic mechanisms with depression, but APR has not been studied in this disorder. Forty-one panic patients in the first stages of their illness were compared with 32 healthy subjects of comparable sex, age, and body mass index. Clinical diagnosis was established with the mini international neuropsychiatric interview, and severity with the panic disorder severity scale and the CGI scale. Laboratory determinations included four acute phase proteins (APPs) [albumin, gammaglobulins, fibrinogen, C-reactive-protein (CRP)] and basal cortisol level. Patients were studied after 8-wk follow-up taking selective serotonin reuptake inhibitors (SSRIs) to assess the evolution of the APPs. Gammaglobulin levels were lower, and both cortisol and CRP levels were higher in PD patients than in controls. APP did not differ between patients with or without agoraphobia. At follow-up, patients who responded to SSRIs presented a decrease in albumin levels, and a trend towards a decrease in cortisol and CRP compared with levels at intake. The conclusions of this study are that there is an APR in patients suffering from PD, and this APR tends to diminish after a successful treatment with SSRIs. PMID:15927091

  11. Green synthesis of bacterial mediated anti-proliferative gold nanoparticles: inducing mitotic arrest (G2/M phase) and apoptosis (intrinsic pathway).

    PubMed

    Kumar, C Ganesh; Poornachandra, Y; Chandrasekhar, Cheemalamarri

    2015-11-28

    The physiochemical and biological properties of microbial derived gold nanoparticles have potential applications in various biomedical domains as well as in cancer therapy. We have fabricated anti-proliferative bacterial mediated gold nanoparticles (b-Au NPs) using a culture supernatant of Streptomyces clavuligerus and later characterized them by UV-visible, TEM, DLS, XRD and FT-IR spectroscopic techniques. The capping agent responsible for the nanoparticle formation was characterized based on SDS-PAGE and MALDI-TOF-MS analyses. They were tested for anticancer activity in A549, HeLa and DU145 cell lines. The biocompatibility and non-toxic nature of the nanoparticles were tested on normal human lung cell line (MRC-5). The b-Au NPs induced the cell cycle arrest in G2/M phase and also inhibited the microtubule assembly in DU145 cells. Mechanistic studies, such as ROS, MMP, Cyt-c, GSH, caspases 9, 8 and 3 activation and the Annexin V-FITC staining, along with the above parameters tested provided sufficient evidence that the b-Au NPs induced apoptosis through the intrinsic pathway. The results supported the use of b-Au NPs for future therapeutic application in cancer therapy and other biomedical applications. PMID:26503300

  12. The Intrinsically Disordered C-RING Biomineralization Protein, AP7, Creates Protein Phases That Introduce Nanopatterning and Nanoporosities into Mineral Crystals

    PubMed Central

    2015-01-01

    We report an interesting process whereby the formation of nanoparticle assemblies on and nanoporosities within calcite crystals is directed by an intrinsically disordered C-RING mollusk shell nacre protein, AP7. Under mineralization conditions, AP7 forms protein phases that direct the nucleation of ordered calcite nanoparticles via a repetitive protein phase deposition process onto calcite crystals. These organized nanoparticles are separated by gaps or spaces that become incorporated into the forming bulk crystal as nanoporosities. This is an unusual example of organized nanoparticle biosynthesis and mineral modification directed by a C-RING protein phase. PMID:24977921

  13. Inverted optical intrinsic response accompanied by decreased cerebral blood flow are related to both neuronal inhibition and excitation

    PubMed Central

    Ma, Zengguang; Cao, Pengjia; Sun, Pengcheng; Zhao, Linna; Li, Liming; Tong, Shanbao; Lu, Yiliang; Yan, Yan; Chen, Yao; Chai, Xinyu

    2016-01-01

    Negative hemodynamic response has been widely reported in blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging studies, however its origin is still controversial. Optical intrinsic signal (OIS) imaging can be used to study brain activity by simultaneously recording hemodynamic signals at different wavelengths with high spatial resolution. In this study, we found transcorneal electrical stimulation (TcES) could elicit both positive OIS response (POR) and negative OIS response (NOR) in cats’ visual cortex. We then investigated the property of this negative response to TcES and its relationship with cerebral blood flow (CBF) and neuronal activity. Results from laser speckle contrast imaging showed decreased CBF in the NOR region while increased CBF in the POR region. Both planar and laminar electrophysiological recordings in the middle (500–700 μm) cortical layers demonstrated that decreased and increased neuronal activities were coexisted in the NOR region. Furthermore, decreased neuronal activity was also detected in the deep cortical layers in the NOR region. This work provides evidence that the negative OIS together with the decreased CBF should be explained by mechanisms of both neuronal inhibition and excitation within middle cortical layers. Our results would be important for interpreting neurophysiological mechanisms underlying the negative BOLD signals. PMID:26860040

  14. IDO2 Modulates T Cell-Dependent Autoimmune Responses through a B Cell-Intrinsic Mechanism.

    PubMed

    Merlo, Lauren M F; DuHadaway, James B; Grabler, Samantha; Prendergast, George C; Muller, Alexander J; Mandik-Nayak, Laura

    2016-06-01

    Mechanistic insight into how adaptive immune responses are modified along the self-nonself continuum may offer more effective opportunities to treat autoimmune disease, cancer, and other sterile inflammatory disorders. Recent genetic studies in the KRN mouse model of rheumatoid arthritis demonstrate that the immunomodulatory molecule IDO2 modifies responses to self-antigens; however, the mechanisms involved are obscure. In this study, we show that IDO2 exerts a critical function in B cells to support the generation of autoimmunity. In experiments with IDO2-deficient mice, adoptive transplant experiments demonstrated that IDO2 expression in B cells was both necessary and sufficient to support robust arthritis development. IDO2 function in B cells was contingent on a cognate, Ag-specific interaction to exert its immunomodulatory effects on arthritis development. We confirmed a similar requirement in an established model of contact hypersensitivity, in which IDO2-expressing B cells are required for a robust inflammatory response. Mechanistic investigations showed that IDO2-deficient B cells lacked the ability to upregulate the costimulatory marker CD40, suggesting IDO2 acts at the T-B cell interface to modulate the potency of T cell help needed to promote autoantibody production. Overall, our findings revealed that IDO2 expression by B cells modulates autoimmune responses by supporting the cross talk between autoreactive T and B cells. PMID:27183624

  15. Cholinergic Responses and Intrinsic Membrane Properties of Developing Thalamic Parafascicular Neurons

    PubMed Central

    Ye, Meijun; Hayar, Abdallah; Garcia-Rill, Edgar

    2009-01-01

    Parafascicular (Pf) neurons receive cholinergic input from the pedunculopontine nucleus (PPN), which is active during waking and REM sleep. There is a developmental decrease in REM sleep in humans between birth and puberty and 10–30 days in rat. Previous studies have established an increase in muscarinic and 5-HT1 serotonergic receptor–mediated inhibition and a transition from excitatory to inhibitory GABAA responses in the PPN during the developmental decrease in REM sleep. However, no studies have been conducted on the responses of Pf cells to the cholinergic input from the PPN during development, which is a major target of ascending cholinergic projections and may be an important mechanism for the generation of rhythmic oscillations in the cortex. Whole cell patch-clamp recordings were performed in 9- to 20-day-old rat Pf neurons in parasagittal slices, and responses to the cholinergic agonist carbachol (CAR) were determined. Three types of responses were identified: inhibitory (55.3%), excitatory (31.1%), and biphasic (fast inhibitory followed by slow excitatory, 6.8%), whereas 6.8% of cells showed no response. The proportion of CAR-inhibited Pf neurons increased with development. Experiments using cholinergic antagonists showed that M2 receptors mediated the inhibitory response, whereas excitatory modulation involved M1, nicotinic, and probably M3 or M5 receptors, and the biphasic response was caused by the activation of multiple types of muscarinic receptors. Compared with CAR-inhibited cells, CAR-excited Pf cells showed 1) a decreased membrane time constant, 2) higher density of hyperpolarization-activated channels (Ih), 3) lower input resistance (Rin), 4) lower action potential threshold, and 5) shorter half-width duration of action potentials. Some Pf cells exhibited spikelets, and all were excited by CAR. During development, we observed decreases in Ih density, Rin, time constant, and action potential half-width. These results suggest that cholinergic

  16. Cholinergic responses and intrinsic membrane properties of developing thalamic parafascicular neurons.

    PubMed

    Ye, Meijun; Hayar, Abdallah; Garcia-Rill, Edgar

    2009-08-01

    Parafascicular (Pf) neurons receive cholinergic input from the pedunculopontine nucleus (PPN), which is active during waking and REM sleep. There is a developmental decrease in REM sleep in humans between birth and puberty and 10-30 days in rat. Previous studies have established an increase in muscarinic and 5-HT1 serotonergic receptor-mediated inhibition and a transition from excitatory to inhibitory GABA(A) responses in the PPN during the developmental decrease in REM sleep. However, no studies have been conducted on the responses of Pf cells to the cholinergic input from the PPN during development, which is a major target of ascending cholinergic projections and may be an important mechanism for the generation of rhythmic oscillations in the cortex. Whole cell patch-clamp recordings were performed in 9- to 20-day-old rat Pf neurons in parasagittal slices, and responses to the cholinergic agonist carbachol (CAR) were determined. Three types of responses were identified: inhibitory (55.3%), excitatory (31.1%), and biphasic (fast inhibitory followed by slow excitatory, 6.8%), whereas 6.8% of cells showed no response. The proportion of CAR-inhibited Pf neurons increased with development. Experiments using cholinergic antagonists showed that M2 receptors mediated the inhibitory response, whereas excitatory modulation involved M1, nicotinic, and probably M3 or M5 receptors, and the biphasic response was caused by the activation of multiple types of muscarinic receptors. Compared with CAR-inhibited cells, CAR-excited Pf cells showed 1) a decreased membrane time constant, 2) higher density of hyperpolarization-activated channels (I(h)), 3) lower input resistance (R(in)), 4) lower action potential threshold, and 5) shorter half-width duration of action potentials. Some Pf cells exhibited spikelets, and all were excited by CAR. During development, we observed decreases in I(h) density, R(in), time constant, and action potential half-width. These results suggest that

  17. Cell Intrinsic and Extrinsic Activators of the Unfolded Protein Response in Cancer: Mechanisms and Targets for Therapy

    PubMed Central

    Tameire, Feven; Verginadis, Ioannis I.; Koumenis, Constantinos

    2015-01-01

    A variety of cell intrinsic or extrinsic stresses evoke perturbations in the folding environment of the endoplasmic reticulum (ER), collectively known as ER stress. Adaptation to stress and reestablishment of ER homeostasis is achieved by activation of an integrated signal transduction pathway called the unfolded protein response (UPR). Both ER stress and UPR activation have been implicated in a variety of human cancers. Although at early stages, or physiological conditions of ER stress, the UPR generally promotes survival, when the stress becomes more stringent or prolonged, its role can switch to a pro-cell death one. Here, we discuss historical and recent evidence supporting an involvement of the UPR in malignancy, describe the main mechanisms by which how tumor cells overcome ER stress to promote their survival, tumor progression and metastasis and discuss the current state of efforts to develop therapeutic approaches of targeting the UPR. PMID:25920797

  18. Intrinsic diffusion simulation for single-phase multicomponent systems and its application for the analysis of the Darken-Manning and jump frequency formalisms

    NASA Astrophysics Data System (ADS)

    Kulkarni, Nagraj Sheshgiri

    A multicomponent, single-phase, diffusion simulation based on Darken's treatment of intrinsic diffusion has been developed, which provides all the information available from an intrinsic diffusion experiment, including composition profiles and diffusion paths, lattice shifts and velocities, intrinsic and interdiffusion fluxes, as well as fluxes and mean velocities in different frames of reference. The various steps involved in the simulation are discussed and the self-consistency of the simulation is tested with the aid of model systems having constant and variable molar volumes. After an examination of the historical development of the Darken-Manning theories and a brief discussion of previous tests in the literature, a systematic procedure for the comprehensive assessment of these theories is proposed in which the intrinsic diffusion simulation developed in this work occupies a central role. This procedure is then utilized to perform an assessment of the Darken-Manning relations for four binary systems: Ag-Cd, Au-Ni, Cu-Zn and Cu-Ni. It is shown that the Darken-Manning relations that provide the connection between the tracer, intrinsic and interdiffusion coefficients, are unsatisfactory. Hence, it is suggested that the development of multicomponent diffusion databases, which often use the Darken relations for the evaluation of the phenomenological coefficients, may be compromised. As an alternative to the traditional phenomenological formalism of multicomponent diffusion, a kinetic formalism based on atom jump frequencies is proposed. An expression for the intrinsic flux in terms of an unbiased and a biased component is derived. It is demonstrated with the aid of the simulation for the Cu-Zn system, that the biased flux may be evaluated from the experimental intrinsic flux and the unbiased flux (obtained from the tracer jump frequency). An unbiased jump frequency formalism that utilizes effective rather than tracer jump frequencies and avoids the complexities

  19. Control of the Acute Phase Response

    PubMed Central

    Kushner, Irving; Broder, Martin L.; Karp, David

    1978-01-01

    In order to investigate the magnitude and kinetics of the C-reactive protein (CRP) response after differing degrees of tissue injury, we studied changes in serum concentration of this acute phase protein in 19 patients after mild or extensive acute myocardial infarction. An increase in serum CRP concentration was seen in all patients. The rate of increase in concentration was found to be exponential, with a mean hourly rate constant for the entire group of patients of 0.085 (doubling time, 8.2 h). Patients with extensive infarction attained mean serum CRP levels about 4 times as great as did patients with mild infarction. No difference could be shown in the mean rate constant between these groups, the greater CRP response in the former group resulting principally from a more protracted period of rise in serum CRP concentration. A lag period before serum CRP levels began to rise was noted in only 4 of the 13 patients in whom this could be assessed. 7 of 10 patients with presumed unstable angina (coronary insufficiency) showed no rise in CRP concentration, while a small increase as noted in 3 patients. The data suggest that acute tissue injury, such as myocardial infarction, rapidly leads to acceleration in synthesis of CRP, and that the duration of this period of acceleration is related to the extent of tissue injury. PMID:621273

  20. Role of DNA damage response pathways in preventing carcinogenesis caused by intrinsic replication stress.

    PubMed

    Wallace, M D; Southard, T L; Schimenti, K J; Schimenti, J C

    2014-07-10

    Defective DNA replication can result in genomic instability, cancer and developmental defects. To understand the roles of DNA damage response (DDR) genes on carcinogenesis in mutants defective for core DNA replication components, we utilized the Mcm4(Chaos3/Chaos3) ('Chaos3') mouse model that, by virtue of an amino-acid alteration in MCM4 that destabilizes the MCM2-7 DNA replicative helicase, has fewer dormant replication origins and an increased number of stalled replication forks. This leads to genomic instability and cancer in most Chaos3 mice. We found that animals doubly mutant for Chaos3 and components of the ataxia telangiectasia-mutated (ATM) double-strand break response pathway (Atm, p21/Cdkn1a and Chk2/Chek2) had decreased tumor latency and/or increased tumor susceptibility. Tumor latency and susceptibility differed between genetic backgrounds and genders, with females demonstrating an overall greater cancer susceptibility to Atm and p21 deficiency than males. Atm deficiency was semilethal in the Chaos3 background and impaired embryonic fibroblast proliferation, suggesting that ATM drug inhibitors might be useful against tumors with DNA replication defects. Hypomorphism for the 9-1-1 component Hus1 did not affect tumor latency or susceptibility in Chaos3 animals, and tumors in these mice did not exhibit impaired ATR pathway signaling. These and other data indicate that under conditions of systemic replication stress, the ATM pathway is particularly important both for cancer suppression and viability during development. PMID:23975433

  1. Resonant Phase Escape from the First Resistive State of Bi2Sr2CaCu2Oy Intrinsic Josephson Junctions under Strong Microwave Irradiation

    NASA Astrophysics Data System (ADS)

    Takahashi, Yusaku; Kakehi, Daiki; Takekoshi, Shuho; Ishikawa, Kazuki; Ayukawa, Shin-ya; Kitano, Haruhisa

    2016-07-01

    We report a study of the phase escape in Bi2Sr2CaCu2Oy intrinsic Josephson junctions under the strong microwave irradiation, focusing on the switch from the first resistive state (2nd SW). The resonant double-peak structure is clearly observed in the switching current distributions below 10 K and is successfully explained by a quantum-mechanical model on the quantum phase escape under the strong microwave field. These results provide the first evidence for the formation of the energy level quantization for the 2nd SW, supporting that the macroscopic quantum tunneling for the 2nd SW survives up to ˜10 K.

  2. On the Firing Rate Dependency of the Phase Response Curve of Rat Purkinje Neurons In Vitro

    PubMed Central

    Couto, João; Linaro, Daniele; De Schutter, E; Giugliano, Michele

    2015-01-01

    Synchronous spiking during cerebellar tasks has been observed across Purkinje cells: however, little is known about the intrinsic cellular mechanisms responsible for its initiation, cessation and stability. The Phase Response Curve (PRC), a simple input-output characterization of single cells, can provide insights into individual and collective properties of neurons and networks, by quantifying the impact of an infinitesimal depolarizing current pulse on the time of occurrence of subsequent action potentials, while a neuron is firing tonically. Recently, the PRC theory applied to cerebellar Purkinje cells revealed that these behave as phase-independent integrators at low firing rates, and switch to a phase-dependent mode at high rates. Given the implications for computation and information processing in the cerebellum and the possible role of synchrony in the communication with its post-synaptic targets, we further explored the firing rate dependency of the PRC in Purkinje cells. We isolated key factors for the experimental estimation of the PRC and developed a closed-loop approach to reliably compute the PRC across diverse firing rates in the same cell. Our results show unambiguously that the PRC of individual Purkinje cells is firing rate dependent and that it smoothly transitions from phase independent integrator to a phase dependent mode. Using computational models we show that neither channel noise nor a realistic cell morphology are responsible for the rate dependent shift in the phase response curve. PMID:25775448

  3. Novel Role for Protein Inhibitor of Activated STAT 4 (PIAS4) in the Restriction of Herpes Simplex Virus 1 by the Cellular Intrinsic Antiviral Immune Response

    PubMed Central

    Conn, Kristen L.; Wasson, Peter; McFarlane, Steven; Tong, Lily; Brown, James R.; Grant, Kyle G.; Domingues, Patricia

    2016-01-01

    ABSTRACT Small ubiquitin-like modifier (SUMO) is used by the intrinsic antiviral immune response to restrict viral pathogens, such as herpes simplex virus 1 (HSV-1). Despite characterization of the host factors that rely on SUMOylation to exert their antiviral effects, the enzymes that mediate these SUMOylation events remain to be defined. We show that unconjugated SUMO levels are largely maintained throughout infection regardless of the presence of ICP0, the HSV-1 SUMO-targeted ubiquitin ligase. Moreover, in the absence of ICP0, high-molecular-weight SUMO-conjugated proteins do not accumulate if HSV-1 DNA does not replicate. These data highlight the continued importance for SUMO signaling throughout infection. We show that the SUMO ligase protein inhibitor of activated STAT 4 (PIAS4) is upregulated during HSV-1 infection and localizes to nuclear domains that contain viral DNA. PIAS4 is recruited to sites associated with HSV-1 genome entry through SUMO interaction motif (SIM)-dependent mechanisms that are destabilized by ICP0. In contrast, PIAS4 accumulates in replication compartments through SIM-independent mechanisms irrespective of ICP0 expression. Depletion of PIAS4 enhances the replication of ICP0-null mutant HSV-1, which is susceptible to restriction by the intrinsic antiviral immune response. The mechanisms of PIAS4-mediated restriction are synergistic with the restriction mechanisms of a characterized intrinsic antiviral factor, promyelocytic leukemia protein, and are antagonized by ICP0. We provide the first evidence that PIAS4 is an intrinsic antiviral factor. This novel role for PIAS4 in intrinsic antiviral immunity contrasts with the known roles of PIAS proteins as suppressors of innate immunity. IMPORTANCE Posttranslational modifications with small ubiquitin-like modifier (SUMO) proteins regulate multiple aspects of host immunity and viral replication. The protein inhibitor of activated STAT (PIAS) family of SUMO ligases is predominantly associated

  4. Microstructure Based Modeling of β Phase Influence on Mechanical Response of Cast AM Series Mg Alloys

    SciTech Connect

    Barker, Erin I.; Choi, Kyoo Sil; Sun, Xin; Deda, Erin; Allison, John; Li, Mei; Forsmark, Joy; Zindel, Jacob; Godlewski, Larry

    2014-09-30

    Magnesium alloys have become popular alternatives to aluminums and steels for the purpose of vehicle light-weighting. However, Mg alloys are hindered from wider application due to limited ductility as well as poor creep and corrosion performance. Understanding the impact of microstructural features on bulk response is key to improving Mg alloys for more widespread use and for moving towards truly predicting modeling capabilities. This study focuses on modeling the intrinsic features, particularly volume fraction and morphology of beta phase present, of cast Mg alloy microstructure and quantifying their impact on bulk performance. Computational results are compared to experimental measurements of cast plates of Mg alloy with varying aluminum content.

  5. Intrinsic n

    SciTech Connect

    Zhang, S. B.; Wei, S.-H.; Zunger, Alex

    2001-02-15

    ZnO typifies a class of materials that can be doped via native defects in only one way: either n type or p type. We explain this asymmetry in ZnO via a study of its intrinsic defect physics, including Zn{sub O}, Zn{sub i}, V{sub O}, O{sub i}, and V{sub Zn} and n-type impurity dopants, Al and F. We find that ZnO is n type at Zn-rich conditions. This is because (i) the Zn interstitial, Zn{sub i}, is a shallow donor, supplying electrons; (ii) its formation enthalpy is low for both Zn-rich and O-rich conditions, so this defect is abundant; and (iii) the native defects that could compensate the n-type doping effect of Zn{sub i} (interstitial O, O{sub i}, and Zn vacancy, V{sub Zn}), have high formation enthalpies for Zn-rich conditions, so these ''electron killers'' are not abundant. We find that ZnO cannot be doped p type via native defects (O{sub i},V{sub Zn}) despite the fact that they are shallow (i.e., supplying holes at room temperature). This is because at both Zn-rich and O-rich conditions, the defects that could compensate p-type doping (V{sub O},Zn{sub i},Zn{sub O}) have low formation enthalpies so these ''hole killers'' form readily. Furthermore, we identify electron-hole radiative recombination at the V{sub O} center as the source of the green luminescence. In contrast, a large structural relaxation of the same center upon double hole capture leads to slow electron-hole recombination (either radiative or nonradiative) responsible for the slow decay of photoconductivity.

  6. Structural ensembles reveal intrinsic disorder for the multi-stimuli responsive bio-mimetic protein Rec1-resilin

    PubMed Central

    Balu, Rajkamal; Knott, Robert; Cowieson, Nathan P.; Elvin, Christopher M.; Hill, Anita J.; Choudhury, Namita R.; Dutta, Naba K.

    2015-01-01

    Rec1-resilin is the first recombinant resilin-mimetic protein polymer, synthesized from exon-1 of the Drosophila melanogaster gene CG15920 that has demonstrated unusual multi-stimuli responsiveness in aqueous solution. Crosslinked hydrogels of Rec1-resilin have also displayed remarkable mechanical properties including near-perfect rubber-like elasticity. The structural basis of these extraordinary properties is not clearly understood. Here we combine a computational and experimental investigation to examine structural ensembles of Rec1-resilin in aqueous solution. The structure of Rec1-resilin in aqueous solutions is investigated experimentally using circular dichroism (CD) spectroscopy and small angle X-ray scattering (SAXS). Both bench-top and synchrotron SAXS are employed to extract structural data sets of Rec1-resilin and to confirm their validity. Computational approaches have been applied to these experimental data sets in order to extract quantitative information about structural ensembles including radius of gyration, pair-distance distribution function, and the fractal dimension. The present work confirms that Rec1-resilin is an intrinsically disordered protein (IDP) that displays equilibrium structural qualities between those of a structured globular protein and a denatured protein. The ensemble optimization method (EOM) analysis reveals a single conformational population with partial compactness. This work provides new insight into the structural ensembles of Rec1-resilin in solution. PMID:26042819

  7. Structural ensembles reveal intrinsic disorder for the multi-stimuli responsive bio-mimetic protein Rec1-resilin.

    PubMed

    Balu, Rajkamal; Knott, Robert; Cowieson, Nathan P; Elvin, Christopher M; Hill, Anita J; Choudhury, Namita R; Dutta, Naba K

    2015-01-01

    Rec1-resilin is the first recombinant resilin-mimetic protein polymer, synthesized from exon-1 of the Drosophila melanogaster gene CG15920 that has demonstrated unusual multi-stimuli responsiveness in aqueous solution. Crosslinked hydrogels of Rec1-resilin have also displayed remarkable mechanical properties including near-perfect rubber-like elasticity. The structural basis of these extraordinary properties is not clearly understood. Here we combine a computational and experimental investigation to examine structural ensembles of Rec1-resilin in aqueous solution. The structure of Rec1-resilin in aqueous solutions is investigated experimentally using circular dichroism (CD) spectroscopy and small angle X-ray scattering (SAXS). Both bench-top and synchrotron SAXS are employed to extract structural data sets of Rec1-resilin and to confirm their validity. Computational approaches have been applied to these experimental data sets in order to extract quantitative information about structural ensembles including radius of gyration, pair-distance distribution function, and the fractal dimension. The present work confirms that Rec1-resilin is an intrinsically disordered protein (IDP) that displays equilibrium structural qualities between those of a structured globular protein and a denatured protein. The ensemble optimization method (EOM) analysis reveals a single conformational population with partial compactness. This work provides new insight into the structural ensembles of Rec1-resilin in solution. PMID:26042819

  8. Structural ensembles reveal intrinsic disorder for the multi-stimuli responsive bio-mimetic protein Rec1-resilin

    NASA Astrophysics Data System (ADS)

    Balu, Rajkamal; Knott, Robert; Cowieson, Nathan P.; Elvin, Christopher M.; Hill, Anita J.; Choudhury, Namita R.; Dutta, Naba K.

    2015-06-01

    Rec1-resilin is the first recombinant resilin-mimetic protein polymer, synthesized from exon-1 of the Drosophila melanogaster gene CG15920 that has demonstrated unusual multi-stimuli responsiveness in aqueous solution. Crosslinked hydrogels of Rec1-resilin have also displayed remarkable mechanical properties including near-perfect rubber-like elasticity. The structural basis of these extraordinary properties is not clearly understood. Here we combine a computational and experimental investigation to examine structural ensembles of Rec1-resilin in aqueous solution. The structure of Rec1-resilin in aqueous solutions is investigated experimentally using circular dichroism (CD) spectroscopy and small angle X-ray scattering (SAXS). Both bench-top and synchrotron SAXS are employed to extract structural data sets of Rec1-resilin and to confirm their validity. Computational approaches have been applied to these experimental data sets in order to extract quantitative information about structural ensembles including radius of gyration, pair-distance distribution function, and the fractal dimension. The present work confirms that Rec1-resilin is an intrinsically disordered protein (IDP) that displays equilibrium structural qualities between those of a structured globular protein and a denatured protein. The ensemble optimization method (EOM) analysis reveals a single conformational population with partial compactness. This work provides new insight into the structural ensembles of Rec1-resilin in solution.

  9. The intrinsic cephalosporin resistome of Listeria monocytogenes in the context of stress response, gene regulation, pathogenesis and therapeutics.

    PubMed

    Krawczyk-Balska, A; Markiewicz, Z

    2016-02-01

    Intrinsic resistance to antibiotics is a serious therapeutic problem in the case of many bacterial species. The Gram-positive human pathogen Listeria monocytogenes is intrinsically resistant to broad spectrum cephalosporin antibiotics, which are commonly used in therapy of bacterial infections. Besides three penicillin-binding proteins the intrinsic cephalosporin resistome of L. monocytogenes includes multidrug resistance transporter transporters, proteins involved in peptidoglycan biosynthesis and modification, cell envelope proteins with structural or general detoxification function, cytoplasmic proteins with unknown function and regulatory proteins. Analysis of the regulation of the expression of genes involved in the intrinsic resistance of L. monocytogenes to cephalosporins highlights the high complexity of control of the intrinsic resistance phenotype. The regulation of the transcription of the intrinsic resistome determinants involves the activity of eight regulators, namely LisR, CesR, LiaR, VirR, σ(B) , σ(H) , σ(L) and PrfA, of which the most prominent role play LisR, CesR and σ(B) . Furthermore, the vast majority of the intrinsic resistome determinants contribute to the tolerance of different stress conditions and virulence. A study indicates that O-acetyltransferase OatA is the most promising candidate for co-drug development since an agent targeting OatA should sensitize L. monocytogenes to certain antibiotics, therefore improving the efficacy of listeriosis treatment as well as food preservation measures. PMID:26509460

  10. The MisR Response Regulator Is Necessary for Intrinsic Cationic Antimicrobial Peptide and Aminoglycoside Resistance in Neisseria gonorrhoeae.

    PubMed

    Kandler, Justin L; Holley, Concerta L; Reimche, Jennifer L; Dhulipala, Vijaya; Balthazar, Jacqueline T; Muszyński, Artur; Carlson, Russell W; Shafer, William M

    2016-08-01

    During infection, the sexually transmitted pathogen Neisseria gonorrhoeae (the gonococcus) encounters numerous host-derived antimicrobials, including cationic antimicrobial peptides (CAMPs) produced by epithelial and phagocytic cells. CAMPs have both direct and indirect killing mechanisms and help link the innate and adaptive immune responses during infection. Gonococcal CAMP resistance is likely important for avoidance of host nonoxidative killing systems expressed by polymorphonuclear granulocytes (e.g., neutrophils) and intracellular survival. Previously studied gonococcal CAMP resistance mechanisms include modification of lipid A with phosphoethanolamine by LptA and export of CAMPs by the MtrCDE efflux pump. In the related pathogen Neisseria meningitidis, a two-component regulatory system (2CRS) termed MisR-MisS has been shown to contribute to the capacity of the meningococcus to resist CAMP killing. We report that the gonococcal MisR response regulator but not the MisS sensor kinase is involved in constitutive and inducible CAMP resistance and is also required for intrinsic low-level resistance to aminoglycosides. The 4- to 8-fold increased susceptibility of misR-deficient gonococci to CAMPs and aminoglycosides was independent of phosphoethanolamine decoration of lipid A and the levels of the MtrCDE efflux pump and seemed to correlate with a general increase in membrane permeability. Transcriptional profiling and biochemical studies confirmed that expression of lptA and mtrCDE was not impacted by the loss of MisR. However, several genes encoding proteins involved in membrane integrity and redox control gave evidence of being MisR regulated. We propose that MisR modulates the levels of gonococcal susceptibility to antimicrobials by influencing the expression of genes involved in determining membrane integrity. PMID:27216061

  11. Geometric, electronic and intrinsic chemical reactivity properties of mono- and bi-substituted quinoline derivatives for the ground state in gas phase

    NASA Astrophysics Data System (ADS)

    Neira Bueno, O. L.; Hincapié H, L.; García Madrid, C.

    2016-02-01

    The study of geometric, electronic properties and intrinsic chemical reactivity is presented for the case of Quinoline and three-derived molecules (4-Amino-Quinoline, 3- Phenyl-Quinoline, 4-Amino-3-phenylquinoline). The study was carried for the ground state in gas phase in the context of the functional theory density using B3LYP/6 31+G (d) model. The purpose of the study is aimed for identifying a compound derived from quinoline, on based to mono- or bi-substitution, using the amino fragment and the phenyl group.

  12. Dielectric behaviors of Aurivillius Bi5Ti3Fe0.5Cr0.5O15 multiferroic polycrystals: Determining the intrinsic magnetoelectric responses by impedance spectroscopy

    PubMed Central

    Bai, Wei; Chen, Chao; Yang, Jing; Zhang, Yuanyuan; Qi, Ruijuan; Huang, Rong; Tang, Xiaodong; Duan, Chun-Gang; Chu, Junhao

    2015-01-01

    Bismuth layer ferroelectrics (BLFs) pioneered by Aurivillius about sixty years ago have been revived recently because of the fatigue- and lead-free behaviors and high Curie temperature, and especially the robust magnetoelectric (ME) effect. However, discerning the intrinsic ME nature, and the inherence between charged defect dipole induced relaxation and spin-related behaviors are still an arduous task. Here, we report a quantitative analysis to reveal the intrinsic spin-lattice coupling in Aurivillius Cr-doped Bi5Ti3FeO15 (BTFCO) multiferroic polycrystals. Dielectric responses are systemically investigated by the temperature-dependent dielectric, module, impedance spectroscopy and equivalent circuit model, and two different dielectric relaxation processes occurred in grain interior of Aurivillius BTFCO polycrystals are clarified. One relaxation is proposed to associate with localized transfer of electrons between Fe3+ and Fe2+ while another one arises from the competition interaction of localized hopping of electrons between Fe3+ and Fe2+ and short-range migration of holes between Cr3+ and Cr6+. The variation of the intrinsic permittivity unambiguously confirms the coupling between spin and dipolar orderings in BTFCO polycrystals. These results offer a vital avenue for identifying the intrinsic and extrinsic signals of the electric and ME responses, and will give significant impetus to exploring the ME electronic devices of Aurivillius materials. PMID:26639998

  13. Dielectric behaviors of Aurivillius Bi5Ti3Fe0.5Cr0.5O15 multiferroic polycrystals: Determining the intrinsic magnetoelectric responses by impedance spectroscopy.

    PubMed

    Bai, Wei; Chen, Chao; Yang, Jing; Zhang, Yuanyuan; Qi, Ruijuan; Huang, Rong; Tang, Xiaodong; Duan, Chun-Gang; Chu, Junhao

    2015-01-01

    Bismuth layer ferroelectrics (BLFs) pioneered by Aurivillius about sixty years ago have been revived recently because of the fatigue- and lead-free behaviors and high Curie temperature, and especially the robust magnetoelectric (ME) effect. However, discerning the intrinsic ME nature, and the inherence between charged defect dipole induced relaxation and spin-related behaviors are still an arduous task. Here, we report a quantitative analysis to reveal the intrinsic spin-lattice coupling in Aurivillius Cr-doped Bi(5)Ti(3)FeO(15) (BTFCO) multiferroic polycrystals. Dielectric responses are systemically investigated by the temperature-dependent dielectric, module, impedance spectroscopy and equivalent circuit model, and two different dielectric relaxation processes occurred in grain interior of Aurivillius BTFCO polycrystals are clarified. One relaxation is proposed to associate with localized transfer of electrons between Fe(3+) and Fe(2+) while another one arises from the competition interaction of localized hopping of electrons between Fe(3+) and Fe(2+) and short-range migration of holes between Cr(3+) and Cr(6+). The variation of the intrinsic permittivity unambiguously confirms the coupling between spin and dipolar orderings in BTFCO polycrystals. These results offer a vital avenue for identifying the intrinsic and extrinsic signals of the electric and ME responses, and will give significant impetus to exploring the ME electronic devices of Aurivillius materials. PMID:26639998

  14. Dielectric behaviors of Aurivillius Bi5Ti3Fe0.5Cr0.5O15 multiferroic polycrystals: Determining the intrinsic magnetoelectric responses by impedance spectroscopy

    NASA Astrophysics Data System (ADS)

    Bai, Wei; Chen, Chao; Yang, Jing; Zhang, Yuanyuan; Qi, Ruijuan; Huang, Rong; Tang, Xiaodong; Duan, Chun-Gang; Chu, Junhao

    2015-12-01

    Bismuth layer ferroelectrics (BLFs) pioneered by Aurivillius about sixty years ago have been revived recently because of the fatigue- and lead-free behaviors and high Curie temperature, and especially the robust magnetoelectric (ME) effect. However, discerning the intrinsic ME nature, and the inherence between charged defect dipole induced relaxation and spin-related behaviors are still an arduous task. Here, we report a quantitative analysis to reveal the intrinsic spin-lattice coupling in Aurivillius Cr-doped Bi5Ti3FeO15 (BTFCO) multiferroic polycrystals. Dielectric responses are systemically investigated by the temperature-dependent dielectric, module, impedance spectroscopy and equivalent circuit model, and two different dielectric relaxation processes occurred in grain interior of Aurivillius BTFCO polycrystals are clarified. One relaxation is proposed to associate with localized transfer of electrons between Fe3+ and Fe2+ while another one arises from the competition interaction of localized hopping of electrons between Fe3+ and Fe2+ and short-range migration of holes between Cr3+ and Cr6+. The variation of the intrinsic permittivity unambiguously confirms the coupling between spin and dipolar orderings in BTFCO polycrystals. These results offer a vital avenue for identifying the intrinsic and extrinsic signals of the electric and ME responses, and will give significant impetus to exploring the ME electronic devices of Aurivillius materials.

  15. Intrinsic cylindrical and spherical waves

    NASA Astrophysics Data System (ADS)

    Ludlow, I. K.

    2008-02-01

    Intrinsic waveforms associated with cylindrical and spherical Bessel functions are obtained by eliminating the factors responsible for the inverse radius and inverse square radius laws of wave power per unit area of wavefront. The resulting expressions are Riccati-Bessel functions for both cases and these can be written in terms of amplitude and phase functions of order v and wave variable z. When z is real, it is shown that a spatial phase angle of the intrinsic wave can be defined and this, together with its amplitude function, is systematically investigated for a range of fixed orders and varying z. The derivatives of Riccati-Bessel functions are also examined. All the component functions exhibit different behaviour in the near field depending on the order being less than, equal to or greater than 1/2. Plots of the phase angle can be used to display the locations of the zeros of the general Riccati-Bessel functions and lead to new relations concerning the ordering of the real zeros of Bessel functions and the occurrence of multiple zeros when the argument of the Bessel function is fixed.

  16. Potent Cell-Intrinsic Immune Responses in Dendritic Cells Facilitate HIV-1-Specific T Cell Immunity in HIV-1 Elite Controllers

    PubMed Central

    Martin-Gayo, Enrique; Buzon, Maria Jose; Ouyang, Zhengyu; Hickman, Taylor; Cronin, Jacqueline; Pimenova, Dina; Walker, Bruce D.; Lichterfeld, Mathias; Yu, Xu G.

    2015-01-01

    The majority of HIV-1 elite controllers (EC) restrict HIV-1 replication through highly functional HIV-1-specific T cell responses, but mechanisms supporting the evolution of effective HIV-1-specific T cell immunity in these patients remain undefined. Cytosolic immune recognition of HIV-1 in conventional dendritic cells (cDC) can facilitate priming and expansion of HIV-1-specific T cells; however, HIV-1 seems to be able to avoid intracellular immune recognition in cDCs in most infected individuals. Here, we show that exposure of cDCs from EC to HIV-1 leads to a rapid and sustained production of type I interferons and upregulation of several interferon-stimulated effector genes. Emergence of these cell-intrinsic immune responses was associated with a reduced induction of SAMHD1 and LEDGF/p75, and an accumulation of viral reverse transcripts, but inhibited by pharmacological blockade of viral reverse transcription or siRNA-mediated silencing of the cytosolic DNA sensor cGAS. Importantly, improved cell-intrinsic immune recognition of HIV-1 in cDCs from elite controllers translated into stronger abilities to stimulate and expand HIV-1-specific CD8 T cell responses. These data suggest an important role of cell-intrinsic type I interferon secretion in dendritic cells for the induction of effective HIV-1-specific CD8 T cells, and may be helpful for eliciting functional T cell immunity against HIV-1 for preventative or therapeutic clinical purposes. PMID:26067651

  17. The effects of cholinergic neuromodulation on neuronal phase-response curves of modeled cortical neurons

    PubMed Central

    Stiefel, Klaus M.; Gutkin, Boris S.; Sejnowski, Terrence J.

    2010-01-01

    The response of an oscillator to perturbations is described by its phase-response curve (PRC), which is related to the type of bifurcation leading from rest to tonic spiking. In a recent experimental study, we have shown that the type of PRC in cortical pyramidal neurons can be switched by cholinergic neuromodulation from type II (biphasic) to type I (monophasic). We explored how intrinsic mechanisms affected by acetylcholine influence the PRC using three different types of neuronal models: a theta neuron, single-compartment neurons and a multi-compartment neuron. In all of these models a decrease in the amount of a spike-frequency adaptation current was a necessary and sufficient condition for the shape of the PRC to change from biphasic (type II) to purely positive (type I). PMID:18784991

  18. Phase response curves elucidating the dynamics of coupled oscillators.

    PubMed

    Granada, A; Hennig, R M; Ronacher, B; Kramer, A; Herzel, H

    2009-01-01

    Phase response curves (PRCs) are widely used in circadian clocks, neuroscience, and heart physiology. They quantify the response of an oscillator to pulse-like perturbations. Phase response curves provide valuable information on the properties of oscillators and their synchronization. This chapter discusses biological self-sustained oscillators (circadian clock, physiological rhythms, etc.) in the context of nonlinear dynamics theory. Coupled oscillators can synchronize with different frequency ratios, can generate toroidal dynamics (superposition of independent frequencies), and may lead to deterministic chaos. These nonlinear phenomena can be analyzed with the aid of a phase transition curve, which is intimately related to the phase response curve. For illustration purposes, this chapter discusses a model of circadian oscillations based on a delayed negative feedback. In a second part, the chapter provides a step-by-step recipe to measure phase response curves. It discusses specifications of this recipe for circadian rhythms, heart rhythms, neuronal spikes, central pattern generators, and insect communication. Finally, it stresses the predictive power of measured phase response curves. PRCs can be used to quantify the coupling strength of oscillations, to classify oscillator types, and to predict the complex dynamics of periodically driven oscillations. PMID:19216921

  19. Federal Radiological Monitoring and Assessment Center: Phase I Response

    SciTech Connect

    C. Riland; D. R. Bowman; R. Lambert; R. Tighe

    1999-09-30

    A Federal Radiological Monitoring and Assessment Center (FRMAC) is established in response to a Lead Federal Agency (LFA) or State request when a radiological emergency is anticipated or has occurred. The FRMAC coordinates the off-site monitoring, assessment, and analysis activities during such an emergency. The FRMAC response is divided into three phases. FRMAC Phase 1 is a rapid, initial-response capability that can interface with Federal or State officials and is designed for a quick response time and rapid radiological data collection and assessment. FRMAC Phase 1 products provide an initial characterization of the radiological situation and information on early health effects to officials responsible for making and implementing protective action decisions.

  20. Low frequency cabin noise reduction based on the intrinsic structural tuning concept: The theory and the experimental results, phase 2. [jet aircraft noise

    NASA Technical Reports Server (NTRS)

    Sengupta, G.

    1978-01-01

    Low frequency cabin noise and sonically induced stresses in an aircraft fuselage may be reduced by intrinsic tuning of the various structural members such as the skin, stringers, and frames and then applying damping treatments on these members. The concept is also useful in identifying the key structural resonance mechanisms controlling the fuselage response to broadband random excitation and in developing suitable damping treatments for reducing the structural response in various frequency ranges. The mathematical proof of the concept and the results of some laboratory and field tests on a group of skin-stringer panels are described. In the so-called stiffness-controlled region, the noise transmission may actually be controlled by stiffener resonances, depending upon the relationship between the natural frequencies of the skin bay and the stiffeners. Therefore, cabin noise in the stiffness-controlled region may be effectively reduced by applying damping treatments on the stiffeners.

  1. Cephalic phase responses to sweet taste.

    PubMed

    Abdallah, L; Chabert, M; Louis-Sylvestre, J

    1997-03-01

    The sweet taste of nonnutritive sweeteners has been reported to increase hunger and food intake through the mechanism of cephalic-phase insulin release (CPIR). We investigated the effect of oral sensation of sweetness on CPIR and other indexes associated with glucose metabolism using nutritive and nonnutritive sweetened tablets as stimuli. At lunchtime, 12 normal-weight men sucked for 5 min a sucrose, an aspartame-polydextrose, or an unsweetened polydextrose tablet (3 g) with no added flavor. The three stimuli were administered in a counterbalanced order, each on a separate day at 1-wk intervals. Blood was drawn continuously for 45 min before and 25 min after the beginning of sucking and samples were collected at 1-min intervals. Spontaneous oscillations in glucose, insulin, and glucagon concentrations were assessed as were increments (slopes) of fatty acid concentrations during the baseline period. The nature of the baseline (oscillations: glucose, insulin, and glucagon; and slopes: fatty acids) was taken into account in the analyses of postexposure events. No CPIR and no significant effect on plasma glucagon or fatty acid concentrations were observed after the three stimuli. However, there was a significant decrease in plasma glucose and insulin after all three stimuli. Only the consumption of the sucrose tablet was followed by a postabsorptive increase in plasma glucose and insulin concentrations starting 17 and 19 min, respectively, after the beginning of sucking. In conclusion, this study suggested that oral stimulation provided by sweet nonflavored tablets is not sufficient for inducing CPIR. PMID:9062523

  2. Observation of intrinsic Josephson effects in tetragonally synthesized single-crystalline NdBa2Cu3O6.65 films grown by tri-phase epitaxy

    NASA Astrophysics Data System (ADS)

    Yun, Kyung Sung; Hatano, Takeshi; Arisawa, Shunichi; Ishii, Akira; Wang, Huabing; Yamashita, Tsutomu; Iguchi, Ienari; Kawasaki, Masashi; Koinuma, Hideomi

    2008-07-01

    In this work twin-free tetragonal NdBa2Cu3O7-δ films were fabricated that exhibited superconductivity with sufficient anisotropy which produced intrinsic Josephson junction (IJJ) characteristics in the films. The intrinsic Josephson effects (IJEs) were observed in oxygen-deficient single-crystalline NdBa2Cu3O6.65 (NBCO) films grown on SrTiO3 (STO) substrates, using tri-phase epitaxy (TPE). The single-crystalline nature of NBCO films on well-matched STO substrates, and the precisely controlled oxygen content of the films, lead to the IJEs of the thin films. Furthermore, the films exhibit high anisotropy and clear multiple-branch structures, with hysteresis observed in the current-voltage characteristics. Periodic Josephson vortex-flow resistance oscillations were also observed for a magnetic field higher than 64 kOe, which was applied normal to the junctions. These results strongly support the single-crystal nature of TPE films, which play an important role in both the fundamental study and the practical applications of high-frequency devices.

  3. Intrinsic MyD88-Akt1-mTOR Signaling Coordinates Disparate Tc17 and Tc1 Responses during Vaccine Immunity against Fungal Pneumonia

    PubMed Central

    Nanjappa, Som Gowda; Hernández-Santos, Nydiaris; Galles, Kevin; Wüthrich, Marcel; Suresh, M.; Klein, Bruce S.

    2015-01-01

    Fungal infections have skyrocketed in immune-compromised patients lacking CD4+ T cells, underscoring the need for vaccine prevention. An understanding of the elements that promote vaccine immunity in this setting is essential. We previously demonstrated that vaccine-induced IL-17A+ CD8+ T cells (Tc17) are required for resistance against lethal fungal pneumonia in CD4+ T cell-deficient hosts, whereas the individual type I cytokines IFN-γ, TNF-α and GM-CSF, are dispensable. Here, we report that T cell-intrinsic MyD88 signals are crucial for these Tc17 cell responses and vaccine immunity against lethal fungal pneumonia in mice. In contrast, IFN-γ+ CD8+ cell (Tc1) responses are largely normal in the absence of intrinsic MyD88 signaling in CD8+ T cells. The poor accumulation of MyD88-deficient Tc17 cells was not linked to an early onset of contraction, nor to accelerated cell death or diminished expression of anti-apoptotic molecules Bcl-2 or Bcl-xL. Instead, intrinsic MyD88 was required to sustain the proliferation of Tc17 cells through the activation of mTOR via Akt1. Moreover, intrinsic IL-1R and TLR2, but not IL-18R, were required for MyD88 dependent Tc17 responses. Our data identify unappreciated targets for augmenting adaptive immunity against fungi. Our findings have implications for designing fungal vaccines and immune-based therapies in immune-compromised patients. PMID:26367276

  4. Intrinsic MyD88-Akt1-mTOR Signaling Coordinates Disparate Tc17 and Tc1 Responses during Vaccine Immunity against Fungal Pneumonia.

    PubMed

    Nanjappa, Som Gowda; Hernández-Santos, Nydiaris; Galles, Kevin; Wüthrich, Marcel; Suresh, M; Klein, Bruce S

    2015-09-01

    Fungal infections have skyrocketed in immune-compromised patients lacking CD4+ T cells, underscoring the need for vaccine prevention. An understanding of the elements that promote vaccine immunity in this setting is essential. We previously demonstrated that vaccine-induced IL-17A+ CD8+ T cells (Tc17) are required for resistance against lethal fungal pneumonia in CD4+ T cell-deficient hosts, whereas the individual type I cytokines IFN-γ, TNF-α and GM-CSF, are dispensable. Here, we report that T cell-intrinsic MyD88 signals are crucial for these Tc17 cell responses and vaccine immunity against lethal fungal pneumonia in mice. In contrast, IFN-γ+ CD8+ cell (Tc1) responses are largely normal in the absence of intrinsic MyD88 signaling in CD8+ T cells. The poor accumulation of MyD88-deficient Tc17 cells was not linked to an early onset of contraction, nor to accelerated cell death or diminished expression of anti-apoptotic molecules Bcl-2 or Bcl-xL. Instead, intrinsic MyD88 was required to sustain the proliferation of Tc17 cells through the activation of mTOR via Akt1. Moreover, intrinsic IL-1R and TLR2, but not IL-18R, were required for MyD88 dependent Tc17 responses. Our data identify unappreciated targets for augmenting adaptive immunity against fungi. Our findings have implications for designing fungal vaccines and immune-based therapies in immune-compromised patients. PMID:26367276

  5. Dose-response and intrinsic efficiency of thermoluminescent dosimeters in a 15 MV clinical photon beam in a liquid water phantom.

    PubMed

    Bravim, A; Sakuraba, R K; Cruz, J C; Campos, L L

    2012-07-01

    This paper compares the performance of CaSO4:Dy and LiF dosimeters irradiated with a 15 MV photon beam of a clinical linear accelerator to 0.1-10 Gy in a liquid water. The dose-response curves are linear up to 5 Gy. The average TL sensitivity of CaSO4:Dy is 26 and 287 times higher than the sensitivities of LiF:Mg,Ti and microLiF:Mg,Ti, respectively. CaSO4:Dy has an intrinsic efficiency 71% and 94% higher than the intrinsic efficiencies of LiF:Mg,Ti and microLiF:Mg,Ti, respectively. PMID:22342311

  6. Glassy phases and driven response of the phase-field-crystal model with random pinning.

    PubMed

    Granato, E; Ramos, J A P; Achim, C V; Lehikoinen, J; Ying, S C; Ala-Nissila, T; Elder, K R

    2011-09-01

    We study the structural correlations and the nonlinear response to a driving force of a two-dimensional phase-field-crystal model with random pinning. The model provides an effective continuous description of lattice systems in the presence of disordered external pinning centers, allowing for both elastic and plastic deformations. We find that the phase-field crystal with disorder assumes an amorphous glassy ground state, with only short-ranged positional and orientational correlations, even in the limit of weak disorder. Under increasing driving force, the pinned amorphous-glass phase evolves into a moving plastic-flow phase and then, finally, a moving smectic phase. The transverse response of the moving smectic phase shows a vanishing transverse critical force for increasing system sizes. PMID:22060323

  7. Adaptive optics and phase diversity imaging for responsive space applications.

    SciTech Connect

    Smith, Mark William; Wick, David Victor

    2004-11-01

    The combination of phase diversity and adaptive optics offers great flexibility. Phase diverse images can be used to diagnose aberrations and then provide feedback control to the optics to correct the aberrations. Alternatively, phase diversity can be used to partially compensate for aberrations during post-detection image processing. The adaptive optic can produce simple defocus or more complex types of phase diversity. This report presents an analysis, based on numerical simulations, of the efficiency of different modes of phase diversity with respect to compensating for specific aberrations during post-processing. It also comments on the efficiency of post-processing versus direct aberration correction. The construction of a bench top optical system that uses a membrane mirror as an active optic is described. The results of characterization tests performed on the bench top optical system are presented. The work described in this report was conducted to explore the use of adaptive optics and phase diversity imaging for responsive space applications.

  8. The antigen-specific response to Toxoplasma gondii profilin, a TLR11/12 ligand, depends on its intrinsic adjuvant properties.

    PubMed

    Hedhli, Dorsaf; Moiré, Nathalie; Akbar, Haroon; Laurent, Fabrice; Héraut, Bruno; Dimier-Poisson, Isabelle; Mévélec, Marie Noëlle

    2016-08-01

    Agonists that activate Toll-like receptors (TLR) are potential vaccine adjuvants. In particular, Toxoplasma gondii profilin (TgPRF) is recognized by TLR11/12 to generate an inflammatory response. Unlike most TLR ligands, TgPRF is also a protein and can therefore simultaneously induce innate and adaptive immune responses. We found that variations in the conformation of TgPRF can affect its ability to induce a TLR11/12-dependent inflammatory response. The secreted recombinant T. gondii (S2-profilin), produced by Schneider 2 cells, has lost its ability to generate an IL-12 response. Reduction of the intramolecular disulfide bonds in S2-profilin rescued the TLR11/12-dependent IL-12 response. Immunization of mice with reduced S2-profilin induced strong cellular and humoral responses compared to mice immunized with unreduced S2-profilin. A mixed Th1/Th2 response was induced with both S2-profilins. However, a more polarized Th1-type response, which was consistent with the IgG2a-polarized humoral response, was observed with reduced S2-profilin. In conclusion, the intrinsic adjuvant properties of TgPRF had significant consequences on the immune response against TgPRF. PMID:26935827

  9. Modeling responses of Daphnia magna to pesticide pulse exposure under varying food conditions: intrinsic versus apparent sensitivity.

    PubMed

    Pieters, Barry J; Jager, Tjalling; Kraak, Michiel H S; Admiraal, Wim

    2006-10-01

    Recent studies showed that limiting food conditions resulted in either increased or decreased sensitivity of Daphnia magna to toxicants. It remained unclear whether these contrasting food-dependent alterations in toxicity resulted from differences in intrinsic sensitivity of the daphnids or from changes in toxicokinetics and resource allocation. It is hypothesized here that, if food level only affects accumulation kinetics and resource allocation, then the intrinsic sensitivity to this toxicant should be the same for all food regimes. This hypothesis was investigated using the DEBtox model, which is based on the theory of Dynamic Energy Budgets. We examined results of two recently conducted life-cycle studies on the combined effects of food level and a pulsed exposure to the pyrethroid insecticide fenvalerate (FV) on D. magna. The model described the effects of the time-varying exposure well, and indicated that when the animals did not die from exposure to FV, full reversibility of toxic effects was possible, allowing a complete recovery. Results revealed furthermore that the data from both studies could be described by the same NECs for survival and assimilation, killing rate and tolerance concentration (132 (49.2-228) x 10(-6) microg/L, 0 (0-1.18 x 10(-5)) microg/L, 74.4 (55.6-96.4) L (microg d)(-1) and 5.39 (2.72-18.5) x 10(-3) microg/L, respectively). It is therefore concluded that food-dependent FV toxicity can be explained by altered toxicokinetics and resource allocation, but not by changes in the intrinsic sensitivity of the daphnids. This study implies that the effect of pesticide application in the field depends on the trophic state of the receiving water body, but also that full recovery of survivors is possible after FV application. PMID:17024561

  10. Elastic response and phase behavior in binary liquid crystal mixtures.

    PubMed

    Sidky, Hythem; Whitmer, Jonathan K

    2016-05-11

    Utilizing density-of-states simulations, we perform a full mapping of the phase behavior and elastic responses of binary liquid crystalline mixtures represented by the multicomponent Lebwohl-Lasher model. Our techniques are able to characterize the complete phase diagram, including nematic-nematic phase separation predicted by mean-field theories, but previously not observed in simulations. Mapping this phase diagram permits detailed study of elastic properties across the miscible nematic region. Importantly, we observe for the first time local phase separation and disordering driven by the application of small linear perturbations near the transition temperature and more significantly through nonlinear stresses. These findings are of key importance in systems of blended nematics which contain particulate inclusions, or are otherwise confined. PMID:27093188

  11. A Cell Line Producing Recombinant Nerve Growth Factor Evokes Growth Responses in Intrinsic and Grafted Central Cholinergic Neurons

    NASA Astrophysics Data System (ADS)

    Ernfors, Patrik; Ebendal, Ted; Olson, Lars; Mouton, Peter; Stromberg, Ingrid; Persson, Hakan

    1989-06-01

    The rat β nerve growth factor (NGF) gene was inserted into a mammalian expression vector and cotransfected with a plasmid conferring resistance to neomycin into mouse 3T3 fibroblasts. From this transfection a stable cell line was selected that contains several hundred copies of the rat NGF gene and produces excess levels of recombinant NGF. Such genetically modified cells were implanted into the rat brain as a probe for in vivo effects of NGF on central nervous system neurons. In a model of the cortical cholinergic deficits in Alzheimer disease, we demonstrate a marked increase in the survival of, and fiber outgrowth from, grafts of fetal basal forebrain cholinergic neurons, as well as stimulation of fiber formation by intact adult intrinsic cholinergic circuits in the cerebral cortex. Adult cholinergic interneurons in intact striatum also sprout vigorously toward implanted fibroblasts. Our results suggest that this model has implications for future treatment of neurodegenerative diseases.

  12. Response of two-phase droplets to intense electromagnetic radiation.

    PubMed

    Spann, J F; Maloney, D J; Lawson, W F; Casleton, K H

    1993-04-20

    The response of two-phase droplets to intense radiant heating is studied to determine the incident power that is required for causing explosive boiling in the liquid phase. The droplets studied consist of strongly absorbing coal particles dispersed in a weakly absorbing water medium. Experiments are performed by confining droplets (radii = 37, 55, and 80 microm) electrodynamically and irradiating them from two sides with pulsed laser beams. Emphasis is placed on the transition region from accelerated droplet vaporization to droplet superheating and explosive boiling. The time scale observed for explosive boiling is more than 2 orders of magnitude longer than published values for pure liquids. The delayed response is the result of energy transfer limitations between the absorbing solid phase and the surrounding liquid. PMID:20820360

  13. Ultrafast response of phase-change memory materials

    NASA Astrophysics Data System (ADS)

    Lindenberg, Aaron

    2015-03-01

    We describe recent experiments probing the first steps in the amorphous-to-crystalline transition that underlies the behavior of phase-change materials, examining both electric-field-driven and optically-driven responses in GeSbTe and AgInSbTe alloys. First measurements using femtosecond x-ray pulses at the Linac Coherent Light Source will be described which enable direct snapshots of these transitions and associated intermediate states. We will also describe studies using single-cycle terahertz pulses as an all-optical means of biasing phase-change materials on femtosecond time-scales in order to examine the threshold-switching response on microscopically relevant time-scales. These studies indicate nonlinear scaling with the applied electric field and field-induced crystallization as evidenced by ultrafast optical reflectivity and conductivity measurements, from which a mechanistic understanding of these phase transitions can be obtained.

  14. Response of two-phase droplets to intense electromagnetic radiation

    NASA Technical Reports Server (NTRS)

    Spann, James F.; Maloney, Daniel J.; Lawson, William F.; Casleton, Kent H.

    1993-01-01

    The response of two-phase droplets to intense radiant heating is studied to determine the incident power that is required for causing explosive boiling in the liquid phase. The droplets studied consist of strongly absorbing coal particles dispersed in a weakly absorbing water medium. Experiments are performed by confining droplets (radii of 37, 55, and 80 microns) electrodynamically and irradiating them from two sides with pulsed laser beams. Emphasis is placed on the transition region from accelerated droplet vaporization to droplet superheating and explosive boiling. The time scale observed for explosive boiling is more than 2 orders of magnitude longer than published values for pure liquids. The delayed response is the result of energy transfer limitations between the absorbing solid phase and the surrounding liquid.

  15. Phase-shifting response to light in older adults

    PubMed Central

    Kim, Seong Jae; Benloucif, Susan; Reid, Kathryn Jean; Weintraub, Sandra; Kennedy, Nancy; Wolfe, Lisa F; Zee, Phyllis C

    2014-01-01

    Abstract Age-related changes in circadian rhythms may contribute to the sleep disruption observed in older adults. A reduction in responsiveness to photic stimuli in the circadian timing system has been hypothesized as a possible reason for the advanced circadian phase in older adults. This project compared phase-shifting responses to 2 h of broad-spectrum white light at moderate and high intensities in younger and older adults. Subjects included 29 healthy young (25.1 ± 4.1 years; male to female ratio: 8: 21) and 16 healthy older (66.5 ± 6.0 years; male to female ratio: 5: 11) subjects, who participated in two 4-night and 3-day laboratory stays, separated by at least 3 weeks. Subjects were randomly assigned to one of three different time-points, 8 h before (−8), 3 h before (−3) or 3 h after (+3) the core body temperature minimum (CBTmin) measured on the baseline night. For each condition, subjects were exposed in a randomized order to 2 h light pulses of two intensities (2000 lux and 8000 lux) during the two different laboratory stays. Phase shifts were analysed according to the time of melatonin midpoint on the nights before and after light exposure. Older subjects in this study showed an earlier baseline phase and lower amplitude of melatonin rhythm compared to younger subjects, but there was no evidence of age-related changes in the magnitude or direction of phase shifts of melatonin midpoint in response to 2 h of light at either 2000 lux or 8000 lux. These results indicate that the acute phase-shifting response to moderate- or high-intensity broad spectrum light is not significantly affected by age. PMID:24144880

  16. Phase responses of harmonics reflected from radio-frequency electronics

    NASA Astrophysics Data System (ADS)

    Mazzaro, Gregory J.; McGowan, Sean F.; Gallagher, Kyle A.; Sherbondy, Kelly D.; Martone, Anthony F.; Narayanan, Ram M.

    2016-05-01

    The phase responses of nonlinear-radar targets illuminated by stepped frequencies are studied. Data is presented for an experimental radar and two commercial electronic targets at short standoff ranges. The amplitudes and phases of harmonics generated by each target at each frequency are captured over a 100-MHz-wide transmit band. As in the authors' prior work, target detection is demonstrated by receiving at least one harmonic of at least one transmit frequency. In the present work, experiments confirm that the phase of a harmonic reflected from a radio-frequency electronic target at a standoff distance is linear versus frequency. Similar to traditional wideband radar, the change of the reflected phase with respect to frequency indicates the range to the nonlinear target.

  17. Theoretical study on single-phase stability and intrinsic defects in different Cu2ZnSn(Se1-xSx)4 alloys

    NASA Astrophysics Data System (ADS)

    Sarker, Pranab; Huda, Muhammad N.

    2015-03-01

    Cu2ZnSn(Se1-xSx)4 (CZTSSe) alloy has been emerged as a potential next generation commercialized photovoltaic cell because of its higher solar-to-current efficiency (12.6 %) over parent compounds Cu2ZnSnS4(CZTS)andCu2ZnSnSe4 (CZTSe). However, the values of composition x in higher efficient CZTSSe (>11%) are not known yet. It has been inferred from the recent theoretical and experimental evidences that 0.375 <= x <= 0.625 (x = alloy ratio per unit cell) could be the range that poses to ensure higher PV efficiency in CZTSSe. The crystal structure of CZTSSe at those x values were determined using density functional theory. In addition, the probability of forming different intrinsic defects in those different CZTSSe alloys were evaluated at various growth conditions determined from chemical potential landscape analysis for the first time. Chemical potential landscape analysis further reveals that CZTSSe alloys have higher single phase stability than that of their parent structures. This work is partially supported by NREL.

  18. Effects of Crowding and Environment on the Evolution of Conformational Ensembles of the Multi-Stimuli-Responsive Intrinsically Disordered Protein, Rec1-Resilin: A Small-Angle Scattering Investigation.

    PubMed

    Balu, Rajkamal; Mata, Jitendra P; Knott, Robert; Elvin, Christopher M; Hill, Anita J; Choudhury, Namita R; Dutta, Naba K

    2016-07-14

    In this study, we explore the overall structural ensembles and transitions of a biomimetic, multi-stimuli-responsive, intrinsically disordered protein (IDP), Rec1-resilin. The structural transition of Rec1-resilin with change in molecular crowding and environment is evaluated using small-angle neutron scattering and small-angle X-ray scattering. The quantitative analyses of the experimental scattering data using a combination of computational models allowed comprehensive description of the structural evolution, organization, and conformational ensembles of Rec1-resilin in response to the changes in concentration, pH, and temperature. Rec1-resilin in uncrowded solutions demonstrates the equilibrium intrinsic structure quality of an IDP with radius of gyration Rg ∼ 5 nm, and a scattering function for the triaxial ellipsoidal model best fit the experimental dataset. On crowding (increase in concentration >10 wt %), Rec1-resilin molecules exert intermolecular repulsive force of interaction, the Rg value reduces with a progressive increase in concentration, and molecular chains transform from a Gaussian coil to a fully swollen coil. It is also revealed that the structural organization of Rec1-resilin dynamically transforms from a rod (pH 2) to coil (pH 4.8) and to globular (pH 12) as a function of pH. The findings further support the temperature-triggered dual-phase-transition behavior of Rec1-resilin, exhibiting rod-shaped structural organization below the upper critical solution temperature (∼4 °C) and a large but compact structure above the lower critical solution temperature (∼75 °C). This work attempted to correlate unusual responsiveness of Rec1-resilin to the evolution of conformational ensembles. PMID:27281267

  19. Development and implementation of a stereoselective normal-phase liquid chromatography-tandem mass spectrometry method for the determination of intrinsic metabolic clearance in human liver microsomes.

    PubMed

    Zhang, Yingru; Caporuscio, Christian; Dai, Jun; Witkusa, Michael; Rose, Anne; Santella, Joseph; D'Arienzo, Celia; Wang-Iverson, David B; Tymiak, Adrienne A

    2008-11-01

    The stereoselective determination of stereoisomers in biological samples provides vital information on stereospecific metabolism and pharmacokinetic profiles of the drugs. Despite the unique advantage and the great success of normal-phase (NP) HPLC for the separations of drug stereoisomers using polysaccharide-type chiral stationary phases (CSPs), the technique is rarely applied to quantitative HPLC-MS-MS bioanalysis. This is, at least in part, due to the incompatibility between the usual mobile phase (n-hexane or n-heptane) in normal-phase HPLC and the MS ionization sources which poses a potential detonation hazard. An environmentally friendly and nonflammable alternative solvent, ethoxynonafluorobutane (ENFB), was reported previously to potentially provide an ideal solution for combining the powers of stereoselective NP chromatographic separation and MS-MS detection. In this study, a stereoselective NP-HPLC-MS-MS method was developed using ENFB to quantify a pair of Bristol Myers Squibb (BMS) proprietary drug stereoisomers and their ketone metabolite for an in vitro study, which demonstrated, for the first time, the practical applicability and utility of ENFB for bioanalysis in pharmaceutical industry. The effects of different organic modifiers and temperature, as well as the comparison between ENFB and the usual solvent, heptane, for the separation, are discussed. The resolution of the stereoisomers was achieved using 63% of 3:1 mixture of ethanol and methanol with 37% ENFB on a Chiralpak AD-H column at 50 degrees C. High sensitivity was obtained using the MS-MS detection in the positive ion atmospheric pressure chemical ionization (APCI) mode. The lower limit of quantitation (LLOQ) for the first stereoisomer and the ketone metabolite was 5 ng/mL, and was 10 ng/mL for the second isomer in the human liver microsome-potassium phosphate buffer matrix. The linear dynamic range of 5-1000 ng/mL for both isomers and 10-1000 ng/mL for the metabolite were demonstrated

  20. Phase response curves in the characterization of epileptiform activity

    NASA Astrophysics Data System (ADS)

    Perez Velazquez, J. L.; Galán, R. F.; Dominguez, L. Garcia; Leshchenko, Y.; Lo, S.; Belkas, J.; Erra, R. Guevara

    2007-12-01

    Coordinated cellular activity is a major characteristic of nervous system function. Coupled oscillator theory offers unique avenues to address cellular coordination phenomena. In this study, we focus on the characterization of the dynamics of epileptiform activity, based on some seizures that manifest themselves with very periodic rhythmic activity, termed absence seizures. Our approach consists in obtaining experimentally the phase response curves (PRCs) in the neocortex and thalamus, and incorporating these PRCs into a model of coupled oscillators. Phase preferences of the stationary states and their stability are determined, and these results from the model are compared with the experimental recordings, and interpreted in physiological terms.

  1. Phase response theory extended to nonoscillatory network components

    NASA Astrophysics Data System (ADS)

    Sieling, Fred H.; Archila, Santiago; Hooper, Ryan; Canavier, Carmen C.; Prinz, Astrid A.

    2012-05-01

    New tools for analysis of oscillatory networks using phase response theory (PRT) under the assumption of pulsatile coupling have been developed steadily since the 1980s, but none have yet allowed for analysis of mixed systems containing nonoscillatory elements. This caveat has excluded the application of PRT to most real systems, which are often mixed. We show that a recently developed tool, the functional phase resetting curve (fPRC), provides a serendipitous benefit: it allows incorporation of nonoscillatory elements into systems of oscillators where PRT can be applied. We validate this method in a model system of neural oscillators and a biological system, the pyloric network of crustacean decapods.

  2. Three phase bone scan interpretation based upon vascular endothelial response

    PubMed Central

    Kumar, Kush

    2015-01-01

    Objectives: A new method of interpretation of Three Phase Bone Scan (TPBS) scan based upon the normal physiological vascular endothelial related response. Materials and Methods: Fifty cases of TPBS were evaluated. Thirteen were normal. In remaining 37 positive studies, 20 showed localized hyperemic response. All localized hyperemic responses except one with vascular endothelial dysfunction were without infection (95.0%). Infection could be ruled out in absence of generalized massive flow and pool response. All 17 cases with generalized massive hyperemic response had infection, consistent with infection or CRPS/RSD. Micro-bacterial or histological confirmation of infection was obtained in 11 cases. All 11 cases with confirmed infection showed generalized massive hyperemic response (100.0%). Two were CRPS/RSD and 2 cases were of cellulitis (100.0%). Among remaining 2, one refused surgery and other was lost to follow-up. Additionally, 20 published cases in the literature of osteomyelitis were also analyzed. Nineteen cases of bone and joint infection, (osteomyelitis/arthritis/cellulitis) except one with endothelial dysfunction showed generalized massive increased flow and pool response (95.0%). All published cases of osteomyelitis in the literature showed generalized massive hyperemic response (100.0%). Results: The data clearly indicated that 100% of the cases of bone infection (osteomyelitis/arthritis/cellulitis) and cases of CRPS/RSD showed generalized massive flow and pool pattern. Infection could be ruled out in absence of generalized massive flow and pool response. All 100% published cases of osteomyelitis in the literature showed positive vascular endothelial response. Conclusion: By incorporating the concept of vascular endothelial related response causing massive vasodilatation in infection, the interpretation of the TPBS can be more précised as it is based upon the normal physiology. Larger studies are recommended. PMID:25829726

  3. Measurement of infinitesimal phase response curves from noisy real neurons

    NASA Astrophysics Data System (ADS)

    Ota, Keisuke; Omori, Toshiaki; Watanabe, Shigeo; Miyakawa, Hiroyoshi; Okada, Masato; Aonishi, Toru

    2011-10-01

    We sought to measure infinitesimal phase response curves (iPRCs) from rat hippocampal CA1 pyramidal neurons. It is difficult to measure iPRCs from noisy neurons because of the dilemma that either the linearity or the signal-to-noise ratio of responses to external perturbations must be sacrificed. To overcome this difficulty, we used an iPRC measurement model formulated as the Langevin phase equation (LPE) to extract iPRCs in the Bayesian scheme. We then simultaneously verified the effectiveness of the measurement model and the reliability of the estimated iPRCs by demonstrating that LPEs with the estimated iPRCs could predict the stochastic behaviors of the same neurons, whose iPRCs had been measured, when they were perturbed by periodic stimulus currents. Our results suggest that the LPE is an effective model for real oscillating neurons and that many theoretical frameworks based on it may be applicable to real nerve systems.

  4. Evaluation of the Phase-Dependent Rhythm Control of Human Walking Using Phase Response Curves.

    PubMed

    Funato, Tetsuro; Yamamoto, Yuki; Aoi, Shinya; Imai, Takashi; Aoyagi, Toshio; Tomita, Nozomi; Tsuchiya, Kazuo

    2016-05-01

    Humans and animals control their walking rhythms to maintain motion in a variable environment. The neural mechanism for controlling rhythm has been investigated in many studies using mechanical and electrical stimulation. However, quantitative evaluation of rhythm variation in response to perturbation at various timings has rarely been investigated. Such a characteristic of rhythm is described by the phase response curve (PRC). Dynamical simulations of human skeletal models with changing walking rhythms (phase reset) described a relation between the effective phase reset on stability and PRC, and phase reset around touch-down was shown to improve stability. A PRC of human walking was estimated by pulling the swing leg, but such perturbations hardly influenced the stance leg, so the relation between the PRC and walking events was difficult to discuss. This research thus examines human response to variations in floor velocity. Such perturbation yields another problem, in that the swing leg is indirectly (and weakly) perturbed, so the precision of PRC decreases. To solve this problem, this research adopts the weighted spike-triggered average (WSTA) method. In the WSTA method, a sequential pulsed perturbation is used for stimulation. This is in contrast with the conventional impulse method, which applies an intermittent impulsive perturbation. The WSTA method can be used to analyze responses to a large number of perturbations for each sequence. In the experiment, perturbations are applied to walking subjects by rapidly accelerating and decelerating a treadmill belt, and measured data are analyzed by the WSTA and impulse methods. The PRC obtained by the WSTA method had clear and stable waveforms with a higher temporal resolution than those obtained by the impulse method. By investigation of the rhythm transition for each phase of walking using the obtained PRC, a rhythm change that extends the touch-down and mid-single support phases is found to occur. PMID:27203839

  5. Evaluation of the Phase-Dependent Rhythm Control of Human Walking Using Phase Response Curves

    PubMed Central

    Yamamoto, Yuki; Aoi, Shinya; Imai, Takashi; Aoyagi, Toshio; Tomita, Nozomi; Tsuchiya, Kazuo

    2016-01-01

    Humans and animals control their walking rhythms to maintain motion in a variable environment. The neural mechanism for controlling rhythm has been investigated in many studies using mechanical and electrical stimulation. However, quantitative evaluation of rhythm variation in response to perturbation at various timings has rarely been investigated. Such a characteristic of rhythm is described by the phase response curve (PRC). Dynamical simulations of human skeletal models with changing walking rhythms (phase reset) described a relation between the effective phase reset on stability and PRC, and phase reset around touch-down was shown to improve stability. A PRC of human walking was estimated by pulling the swing leg, but such perturbations hardly influenced the stance leg, so the relation between the PRC and walking events was difficult to discuss. This research thus examines human response to variations in floor velocity. Such perturbation yields another problem, in that the swing leg is indirectly (and weakly) perturbed, so the precision of PRC decreases. To solve this problem, this research adopts the weighted spike-triggered average (WSTA) method. In the WSTA method, a sequential pulsed perturbation is used for stimulation. This is in contrast with the conventional impulse method, which applies an intermittent impulsive perturbation. The WSTA method can be used to analyze responses to a large number of perturbations for each sequence. In the experiment, perturbations are applied to walking subjects by rapidly accelerating and decelerating a treadmill belt, and measured data are analyzed by the WSTA and impulse methods. The PRC obtained by the WSTA method had clear and stable waveforms with a higher temporal resolution than those obtained by the impulse method. By investigation of the rhythm transition for each phase of walking using the obtained PRC, a rhythm change that extends the touch-down and mid-single support phases is found to occur. PMID:27203839

  6. Normal Caloric Responses during Acute Phase of Vestibular Neuritis

    PubMed Central

    Lee, Sun-Uk; Park, Seong-Ho; Kim, Hyo-Jung; Koo, Ja-Won

    2016-01-01

    Background and Purpose We report a novel finding of caloric conversion from normal responses into unilateral paresis during the acute phase of vestibular neuritis (VN). Methods We recruited 893 patients with a diagnosis of VN at Dizziness Clinic of Seoul National University Bundang Hospital from 2003 to 2014 after excluding 28 patients with isolated inferior divisional VN (n=14) and those without follow-up tests despite normal caloric responses initially (n=14). We retrospectively analyzed the neurotological findings in four (0.5%) of the patients who showed a conversion from initially normal caloric responses into unilateral paresis during the acute phase. Results In those four patients, the initial caloric tests were performed within 2 days of symptom onset, and conversion into unilateral caloric paresis was documented 1–4 days later. The clinical and laboratory findings during the initial evaluation were consistent with VN in all four patients except for normal findings in bedside head impulse tests in one of them. Conclusions Normal findings in caloric tests should be interpreted with caution during the acute phase of suspected VN. Follow-up evaluation should be considered when the findings of the initial caloric test are normal, but VN remains the most plausible diagnosis. PMID:26932259

  7. Pyrotechnic shock response predictions combining statistical energy analysis and local random phase reconstruction.

    PubMed

    Bodin, E; Brévart, B; Wagstaff, P; Borello, G

    2002-07-01

    Numerous pyrotechnic devices are used on satellites to separate structural subsystems, deploy appendages, and activate on-board operating subsystems. The firing of these pyrotechnic mechanisms leads to severe impulsive loads which could sometimes lead to failures in electronic systems. The objective of the present investigation is to assess the relevance of a method combining deterministic calculations and statistical energy analysis to predict the time overall shock environment of electronic equipment components. The methods are applied to the low- and high-frequency ranges, respectively, which may be defined using a modal parameter based on the effective transmissibility. Initially, in order to address the problem of the low-frequency content of the mechanical shock pulse, the linear dynamic response of the equipment was calculated using direct time integration of a finite element model of the structure. The inputs in the form of the accelerations measured in all three directions at each of the four bolted interfaces were injected into the model. The high-frequency content of the shock response is taken into account by considering the intrinsic dynamic filtering of the equipment. This frequency filter magnitude is extrapolated from the transfer function given by statistical energy analysis between the different imposed accelerations and the response accelerations. Their associated phases are synthesized by considering pseudo-modal phase variations around the group velocity of the structural flexural waves. Combining the effects of the high-frequency filter outputs and the low-frequency finite element calculations yields good predictions of the equipment shock time response over the whole frequency range of interest. PMID:12141340

  8. Pyrotechnic shock response predictions combining statistical energy analysis and local random phase reconstruction

    NASA Astrophysics Data System (ADS)

    Bodin, E.; Brevart, B.; Wagstaff, P.; Borello, G.

    2002-07-01

    Numerous pyrotechnic devices are used on satellites to separate structural subsystems, deploy appendages, and activate on-board operating subsystems. The firing of these pyrotechnic mechanisms leads to severe impulsive loads which could sometimes lead to failures in electronic systems. The objective of the present investigation is to assess the relevance of a method combining deterministic calculations and statistical energy analysis to predict the time overall shock environment of electronic equipment components. The methods are applied to the low- and high-frequency ranges, respectively, which may be defined using a modal parameter based on the effective transmissibility. Initially, in order to address the problem of the low-frequency content of the mechanical shock pulse, the linear dynamic response of the equipment was calculated using direct time integration of a finite element model of the structure. The inputs in the form of the accelerations measured in all three directions at each of the four bolted interfaces were injected into the model. The high-frequency content of the shock response is taken into account by considering the intrinsic dynamic filtering of the equipment. This frequency filter magnitude is extrapolated from the transfer function given by statistical energy analysis between the different imposed accelerations and the response accelerations. Their associated phases are synthesized by considering pseudo-modal phase variations around the group velocity of the structural flexural waves. Combining the effects of the high-frequency filter outputs and the low-frequency finite element calculations yields good predictions of the equipment shock time response over the whole frequency range of interest. copyright 2002 Acoustical Society of America.

  9. Activation of Intrinsic Immune Responses and Microglial Phagocytosis in an Ex Vivo Spinal Cord Slice Culture Model of West Nile Virus Infection

    PubMed Central

    Quick, Eamon D.; Leser, J. Smith; Tyler, Kenneth L.

    2014-01-01

    ABSTRACT West Nile virus (WNV) is a neurotropic flavivirus that causes significant neuroinvasive disease involving the brain and/or spinal cord. Experimental mouse models of WNV infection have established the importance of innate and adaptive immune responses in controlling the extent and severity of central nervous system (CNS) disease. However, differentiating between immune responses that are intrinsic to the CNS and those that are dependent on infiltrating inflammatory cells has proven difficult. We used a murine ex vivo spinal cord slice culture (SCSC) model to determine the innate immune processes specific to the CNS during WNV infections. By 7 days after ex vivo infection of SCSCs, the majority of neurons and a substantial percentage of astrocytes were infected with WNV, resulting in apoptotic cell death and astrogliosis. Microglia, the resident immune cells of the CNS, were activated by WNV infection, as exemplified by their amoeboid morphology, the development of filopodia and lamellipodia, and phagocytosis of WNV-infected cells and debris. Microglial cell activation was concomitant with increased expression of proinflammatory cytokines and chemokines, including CXCL10, CXCL1, CCL5, CCL3, CCL2, tumor necrosis factor alpha (TNF-α), TNF-related apoptosis-inducing ligand (TRAIL), and interleukin-6 (IL-6). The application of minocycline, an inhibitor of neuroinflammation, altered the WNV-induced proinflammatory cytokine/chemokine expression profile, with inhibited production of CCL5, CCL2, and IL-6. Our findings establish that CNS-resident cells have the capacity to initiate a robust innate immune response against WNV infection in the absence of infiltrating inflammatory cells and systemic immune responses. IMPORTANCE There are no specific treatments of proven efficacy available for WNV neuroinvasive disease. A better understanding of the pathogenesis of WNV CNS infection is crucial for the rational development of novel therapies. Development of a spinal cord

  10. Intrinsic evolutions of dielectric function and electronic transition in tungsten doping Ge2Sb2Te5 phase change films discovered by ellipsometry at elevated temperatures

    NASA Astrophysics Data System (ADS)

    Guo, S.; Ding, X. J.; Zhang, J. Z.; Hu, Z. G.; Ji, X. L.; Wu, L. C.; Song, Z. T.; Chu, J. H.

    2015-02-01

    Tungsten (W) doping effects on Ge2Sb2Te5 (GSTW) phase change films with different concentrations (3.2, 7.1, and 10.8%) have been investigated by variable-temperature spectroscopic ellipsometry. The dielectric functions from 210 K to 660 K have been evaluated with the aid of Tauc-Lorentz and Drude dispersion models. The analysis of Tauc gap energy (Eg) and partial spectral weight integral reveal the correlation between optical properties and local structural change. The order degree increment and chemical bond change from covalent to resonant should be responsible for band gap narrowing and electronic transition enhancement during the phase change process. It is found that the elevated crystalline temperature for GSTW can be related to improved disorder degree. Furthermore, the shrinkage of Eg for GSTW should be attributed to the enhanced metallicity compared with undoped GST.

  11. Phase response curves for models of earthquake fault dynamics

    NASA Astrophysics Data System (ADS)

    Franović, Igor; Kostić, Srdjan; Perc, Matjaž; Klinshov, Vladimir; Nekorkin, Vladimir; Kurths, Jürgen

    2016-06-01

    We systematically study effects of external perturbations on models describing earthquake fault dynamics. The latter are based on the framework of the Burridge-Knopoff spring-block system, including the cases of a simple mono-block fault, as well as the paradigmatic complex faults made up of two identical or distinct blocks. The blocks exhibit relaxation oscillations, which are representative for the stick-slip behavior typical for earthquake dynamics. Our analysis is carried out by determining the phase response curves of first and second order. For a mono-block fault, we consider the impact of a single and two successive pulse perturbations, further demonstrating how the profile of phase response curves depends on the fault parameters. For a homogeneous two-block fault, our focus is on the scenario where each of the blocks is influenced by a single pulse, whereas for heterogeneous faults, we analyze how the response of the system depends on whether the stimulus is applied to the block having a shorter or a longer oscillation period.

  12. Cephalic phase metabolic responses in normal weight adults.

    PubMed

    Bruce, D G; Storlien, L H; Furler, S M; Chisholm, D J

    1987-08-01

    The presence and physiologic importance of cephalic phase insulin release in humans remains controversial. The aim of these studies was to determine whether cephalic phase insulin release could be demonstrated in normal weight subjects and whether it would be associated with changes in blood glucose, free fatty acid, and pancreatic polypeptide levels. The studies were followed by a hyperglycemic clamp to determine whether cephalic responses would alter overall glucose disposal or glucose-stimulated insulin secretion. In all, 17 subjects were studied on two occasions with and without (control study) presentation of food stimuli. Tease-feeding alone (n = 6), or the administration of a sweet taste alone (aspartame, n = 5) failed to stimulate cephalic responses. However, the presentation of the combined stimuli (tease meals plus sweet taste, n = 7) resulted in a significant fall (P less than .005) in blood glucose levels and a variable rise in serum insulin (% insulin rise 38 +/- 15%, P less than .05) and C-peptide levels (7 +/- 6%, NS) within five minutes of the food presentation when compared with control studies, with no change seen in free fatty acid or pancreatic polypeptide levels. The blood glucose fall correlated strongly (r = .90, P less than .01) with a score of the subjective response to the food and taste.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3298939

  13. Phase response curves for models of earthquake fault dynamics.

    PubMed

    Franović, Igor; Kostić, Srdjan; Perc, Matjaž; Klinshov, Vladimir; Nekorkin, Vladimir; Kurths, Jürgen

    2016-06-01

    We systematically study effects of external perturbations on models describing earthquake fault dynamics. The latter are based on the framework of the Burridge-Knopoff spring-block system, including the cases of a simple mono-block fault, as well as the paradigmatic complex faults made up of two identical or distinct blocks. The blocks exhibit relaxation oscillations, which are representative for the stick-slip behavior typical for earthquake dynamics. Our analysis is carried out by determining the phase response curves of first and second order. For a mono-block fault, we consider the impact of a single and two successive pulse perturbations, further demonstrating how the profile of phase response curves depends on the fault parameters. For a homogeneous two-block fault, our focus is on the scenario where each of the blocks is influenced by a single pulse, whereas for heterogeneous faults, we analyze how the response of the system depends on whether the stimulus is applied to the block having a shorter or a longer oscillation period. PMID:27368770

  14. Collective phase response curves for heterogeneous coupled oscillators

    NASA Astrophysics Data System (ADS)

    Hannay, Kevin M.; Booth, Victoria; Forger, Daniel B.

    2015-08-01

    Phase response curves (PRCs) have become an indispensable tool in understanding the entrainment and synchronization of biological oscillators. However, biological oscillators are often found in large coupled heterogeneous systems and the variable of physiological importance is the collective rhythm resulting from an aggregation of the individual oscillations. To study this phenomena we consider phase resetting of the collective rhythm for large ensembles of globally coupled Sakaguchi-Kuramoto oscillators. Making use of Ott-Antonsen theory we derive an asymptotically valid analytic formula for the collective PRC. A result of this analysis is a characteristic scaling for the change in the amplitude and entrainment points for the collective PRC compared to the individual oscillator PRC. We support the analytical findings with numerical evidence and demonstrate the applicability of the theory to large ensembles of coupled neuronal oscillators.

  15. Antigen Receptor-Intrinsic Non-Self: The Key to Understanding Regulatory Lymphocyte-Mediated Idiotypic Control of Adaptive Immune Responses.

    PubMed

    Lemke, Hilmar

    2016-01-01

    The clone-specific or idiotypic characters of B as well as T cell antigen receptors (BCRs/TCRs) are associated with (1) the third-complementarity-determining regions (CDR3s) that are created during V(D)J recombination (they scarcely occur in antibody light chains) and (2) BCR idiotopes created by somatic hypermutations (SHMs) during immune responses. Therefore, BCR/TCR idiotypic sites are antigen receptor-intrinsic Non-Self (AgR-iNS) portions that fulfill two tasks: serving as a crucial component of the epitope-binding paratope and serving as target sites for anti-idiotypic BCR/TCR paratopes of other anti-Non-Self clones that are contained in both normal repertoires. The antigen-induced immune response is thus directed not only toward the environmental stimulus but also against the AgR-iNS portions of the directly and further activated clones that form a subsiding idiotypic cascade. These idiotypic chain reactions form a completely integrated idiotypic control circuit among B and T cells which contains all regulatory T and B cells. However, this circuit cannot be viewed as a network of fixed interacting nodes but rather uses the genetic Self as reference. Hence, AgR-iNS offers a mechanistic understanding of regulatory lymphocyte-mediated idiotypic control of adaptive immune responses and reconciles clonal selection and idiotypic network theories hitherto believed to be incompatible. PMID:27480901

  16. Allyl isothiocyanate from mustard seed is effective in reducing the levels of volatile sulfur compounds responsible for intrinsic oral malodor.

    PubMed

    Tian, Minmin; Hanley, A Bryan; Dodds, Michael W J

    2013-06-01

    Oral malodor is a major social and psychological issue that affects general populations. Volatile sulfur compounds (VSCs), particularly hydrogen sulfide (H₂S) and methyl mercaptan (CH₃SH), are responsible for most oral malodor. The objectives for this study were to determine whether allyl isothiocyanate (AITC) at an organoleptically acceptable level can eliminate VSCs containing a free thiol moiety and further to elucidate the mechanism of action and reaction kinetics. The study revealed that gas chromatograph with a sulfur detector demonstrated a good linearity, high accuracy and sensitivity on analysis of VSCs. Zinc salts eliminate the headspace level of H₂S but not CH₃SH. AITC eliminates both H₂S and CH₃SH via a nucleophilic addition reaction. In addition, a chemical structure-activity relationship study revealed that the presence of unsaturated group on the side chain of the isothiocyanate accelerates the elimination of VSCs. PMID:23470258

  17. Activation of the Nrf2 response by intrinsic hepatotoxic drugs correlates with suppression of NF-κB activation and sensitizes toward TNFα-induced cytotoxicity.

    PubMed

    Herpers, Bram; Wink, Steven; Fredriksson, Lisa; Di, Zi; Hendriks, Giel; Vrieling, Harry; de Bont, Hans; van de Water, Bob

    2016-05-01

    Drug-induced liver injury (DILI) is an important problem both in the clinic and in the development of new safer medicines. Two pivotal adaptation and survival responses to adverse drug reactions are oxidative stress and cytokine signaling based on the activation of the transcription factors Nrf2 and NF-κB, respectively. Here, we systematically investigated Nrf2 and NF-κB signaling upon DILI-related drug exposure. Transcriptomics analyses of 90 DILI compounds in primary human hepatocytes revealed that a strong Nrf2 activation is associated with a suppression of endogenous NF-κB activity. These responses were translated into quantitative high-content live-cell imaging of induction of a selective Nrf2 target, GFP-tagged Srxn1, and the altered nuclear translocation dynamics of a subunit of NF-κB, GFP-tagged p65, upon TNFR signaling induced by TNFα using HepG2 cells. Strong activation of GFP-Srxn1 expression by DILI compounds typically correlated with suppression of NF-κB nuclear translocation, yet reversely, activation of NF-κB by TNFα did not affect the Nrf2 response. DILI compounds that provided strong Nrf2 activation, including diclofenac, carbamazepine and ketoconazole, sensitized toward TNFα-mediated cytotoxicity. This was related to an adaptive primary protective response of Nrf2, since loss of Nrf2 enhanced this cytotoxic synergy with TNFα, while KEAP1 downregulation was cytoprotective. These data indicate that both Nrf2 and NF-κB signaling may be pivotal in the regulation of DILI. We propose that the NF-κB-inhibiting effects that coincide with a strong Nrf2 stress response likely sensitize liver cells to pro-apoptotic signaling cascades induced by intrinsic cytotoxic pro-inflammatory cytokines. PMID:26026609

  18. The Touch and Zap Method for In Vivo Whole-Cell Patch Recording of Intrinsic and Visual Responses of Cortical Neurons and Glial Cells

    PubMed Central

    Schramm, Adrien E.; Marinazzo, Daniele; Gener, Thomas; Graham, Lyle J.

    2014-01-01

    Whole-cell patch recording is an essential tool for quantitatively establishing the biophysics of brain function, particularly in vivo. This method is of particular interest for studying the functional roles of cortical glial cells in the intact brain, which cannot be assessed with extracellular recordings. Nevertheless, a reasonable success rate remains a challenge because of stability, recording duration and electrical quality constraints, particularly for voltage clamp, dynamic clamp or conductance measurements. To address this, we describe “Touch and Zap”, an alternative method for whole-cell patch clamp recordings, with the goal of being simpler, quicker and more gentle to brain tissue than previous approaches. Under current clamp mode with a continuous train of hyperpolarizing current pulses, seal formation is initiated immediately upon cell contact, thus the “Touch”. By maintaining the current injection, whole-cell access is spontaneously achieved within seconds from the cell-attached configuration by a self-limited membrane electroporation, or “Zap”, as seal resistance increases. We present examples of intrinsic and visual responses of neurons and putative glial cells obtained with the revised method from cat and rat cortices in vivo. Recording parameters and biophysical properties obtained with the Touch and Zap method compare favourably with those obtained with the traditional blind patch approach, demonstrating that the revised approach does not compromise the recorded cell. We find that the method is particularly well-suited for whole-cell patch recordings of cortical glial cells in vivo, targeting a wider population of this cell type than the standard method, with better access resistance. Overall, the gentler Touch and Zap method is promising for studying quantitative functional properties in the intact brain with minimal perturbation of the cell's intrinsic properties and local network. Because the Touch and Zap method is performed semi

  19. Acute phase proteins response to feed deprivation in broiler chickens.

    PubMed

    Najafi, P; Zulkifli, I; Soleimani, A F; Goh, Y M

    2016-04-01

    Feed deprivation in poultry farming imposes some degree of stress to the birds, and adversely affects their well -being. Serum levels of acute phase proteins (APP) are potential physiological indicators of stress attributed to feed deprivation. However, it has not been determined how long it takes for a measurable APP response to stressors to occur in avian species. An experiment was designed to delineate the APP and circulating levels of corticosterone responses in commercial broiler chickens to feed deprivation for 30 h. It was hypothesized that feed deprivation would elicit both APP and corticosterone (CORT) reactions within 30 h that is probably associated with stress of hunger. Twenty-one day old birds were subjected to one of 5 feed deprivation periods: 0 (ad libitum, AL), 6, 12, 18, 24, and 30 h. Upon completion of the deprivation period, blood samples were collected to determine serum CORT, ovotransferrin (OVT), α1-acid glycoprotein (AGP), and ceruloplasmin (CP) concentrations. Results showed that feed deprivation for 24 h or more caused a marked elevation in CORT (P=0.002 and P<0.0001, respectively) when compared to AL. However, increases in AGP (P=0.0005), CP (P=0.0002), and OVT (P=0.0003) were only noted following 30 h of feed deprivation. It is concluded that elicitation of AGP, CP, and OVT response may represent a more chronic stressful condition than CORT response in assessing the well-being of broiler chickens. PMID:26908886

  20. Brown and white adipose tissues: intrinsic differences in gene expression and response to cold exposure in mice

    PubMed Central

    Rosell, Meritxell; Kaforou, Myrsini; Frontini, Andrea; Okolo, Anthony; Chan, Yi-Wah; Nikolopoulou, Evanthia; Millership, Steven; Fenech, Matthew E.; MacIntyre, David; Turner, Jeremy O.; Moore, Jonathan D.; Blackburn, Edith; Gullick, William J.; Cinti, Saverio; Montana, Giovanni; Parker, Malcolm G.

    2014-01-01

    Brown adipocytes dissipate energy, whereas white adipocytes are an energy storage site. We explored the plasticity of different white adipose tissue depots in acquiring a brown phenotype by cold exposure. By comparing cold-induced genes in white fat to those enriched in brown compared with white fat, at thermoneutrality we defined a “brite” transcription signature. We identified the genes, pathways, and promoter regulatory motifs associated with “browning,” as these represent novel targets for understanding this process. For example, neuregulin 4 was more highly expressed in brown adipose tissue and upregulated in white fat upon cold exposure, and cell studies showed that it is a neurite outgrowth-promoting adipokine, indicative of a role in increasing adipose tissue innervation in response to cold. A cell culture system that allows us to reproduce the differential properties of the discrete adipose depots was developed to study depot-specific differences at an in vitro level. The key transcriptional events underpinning white adipose tissue to brown transition are important, as they represent an attractive proposition to overcome the detrimental effects associated with metabolic disorders, including obesity and type 2 diabetes. PMID:24549398

  1. Brown and white adipose tissues: intrinsic differences in gene expression and response to cold exposure in mice.

    PubMed

    Rosell, Meritxell; Kaforou, Myrsini; Frontini, Andrea; Okolo, Anthony; Chan, Yi-Wah; Nikolopoulou, Evanthia; Millership, Steven; Fenech, Matthew E; MacIntyre, David; Turner, Jeremy O; Moore, Jonathan D; Blackburn, Edith; Gullick, William J; Cinti, Saverio; Montana, Giovanni; Parker, Malcolm G; Christian, Mark

    2014-04-15

    Brown adipocytes dissipate energy, whereas white adipocytes are an energy storage site. We explored the plasticity of different white adipose tissue depots in acquiring a brown phenotype by cold exposure. By comparing cold-induced genes in white fat to those enriched in brown compared with white fat, at thermoneutrality we defined a "brite" transcription signature. We identified the genes, pathways, and promoter regulatory motifs associated with "browning," as these represent novel targets for understanding this process. For example, neuregulin 4 was more highly expressed in brown adipose tissue and upregulated in white fat upon cold exposure, and cell studies showed that it is a neurite outgrowth-promoting adipokine, indicative of a role in increasing adipose tissue innervation in response to cold. A cell culture system that allows us to reproduce the differential properties of the discrete adipose depots was developed to study depot-specific differences at an in vitro level. The key transcriptional events underpinning white adipose tissue to brown transition are important, as they represent an attractive proposition to overcome the detrimental effects associated with metabolic disorders, including obesity and type 2 diabetes. PMID:24549398

  2. HGFL supports mammary tumorigenesis by enhancing tumor cell intrinsic survival and influencing macrophage and T-cell responses

    PubMed Central

    Benight, Nancy M.; Wagh, Purnima K.; Zinser, Glendon M.; Peace, Belinda E.; Stuart, William D.; Vasiliauskas, Juozas; Pathrose, Peterson; Starnes, Sandra L.; Waltz, Susan E.

    2015-01-01

    The Ron receptor is overexpressed in human breast cancers and is associated with heightened metastasis and poor survival. Ron overexpression in the mammary epithelium of mice is sufficient to induce aggressive mammary tumors with a high degree of metastasis. Despite the well-documented role of Ron in breast cancer, few studies have examined the necessity of the endogenous Ron ligand, hepatocyte growth factor-like protein (HGFL) in mammary tumorigenesis. Herein, mammary tumor growth and metastasis were examined in mice overexpressing Ron in the mammary epithelium with or without HGFL. HGFL ablation decreased oncogenic Ron activation and delayed mammary tumor initiation. HGFL was important for tumor cell proliferation and survival. HGFL loss resulted in increased numbers of macrophages and T-cells within the tumor. T-cell proliferation and cytotoxicity dramatically increased in HGFL deficient mice. Biochemical analysis of HGFL proficient tumors showed increased local HGFL production, with HGFL loss decreasing β-catenin expression and NF-κB activation. Re-expression of HGFL in HGFL deficient tumor cells stimulated cell migration and invasion with coordinate activation of NF-κB and reduced apoptosis. Together, these results demonstrate critical in vivo functions for HGFL in promoting breast tumorigenesis and suggest that targeting HGFL may inhibit tumor growth and reactivate anti-tumor immune responses. PMID:25938541

  3. Acute phase protein response in the capybara (Hydrochoerus hydrochaeris).

    PubMed

    Bernal, Luis; Feser, Mariane; Martínez-Subiela, Silvia; García-Martínez, Juan D; Cerón, José J; Tecles, Fernando

    2011-10-01

    We evaluated the acute phase protein response in capybaras (Hydrochoerus hydrochaeris). Three animal groups were used: 1) healthy animals (n=30), 2) a group in which experimental inflammation with turpentine was induced (n=6), and 3) a group affected with sarcoptic scabies (n=14) in which 10 animals were treated with ivermectin. Haptoglobin (Hp), acid-soluble glycoprotein (ASG) and albumin were analyzed in all animals. In those treated with turpentine, Hp reached its maximum value at 2 wk with a 2.7-fold increase, whereas ASG increased 1.75-fold and albumin decreased 0.87-fold 1 wk after the induction of inflammation. Capybaras affected with sarcoptic scabies presented increases in Hp and ASG of 4.98- and 3.18-fold, respectively, and a 0.87-fold decrease in albumin, compared with healthy animals. Haptoglobin and ASG can be considered as moderate, positive acute phase proteins in capybaras because they showed less than 10-fold increases after an inflammatory process and reached their peak concentrations 1 wk after the induction of inflammation. Conversely, albumin can be considered a negative acute phase protein in capybaras because it showed a reduction in concentration after inflammatory stimulus. PMID:22102653

  4. Robust Entrainment of Circadian Oscillators Requires Specific Phase Response Curves

    PubMed Central

    Pfeuty, Benjamin; Thommen, Quentin; Lefranc, Marc

    2011-01-01

    The circadian clocks keeping time in many living organisms rely on self-sustained biochemical oscillations entrained by external cues, such as light, to the 24-h cycle induced by Earth's rotation. However, environmental cues are unreliable due to the variability of habitats, weather conditions, or cue-sensing mechanisms among individuals. A tempting hypothesis is that circadian clocks have evolved so as to be robust to fluctuations in the signal that entrains them. To support this hypothesis, we analyze the synchronization behavior of weakly and periodically forced oscillators in terms of their phase response curve (PRC), which measures phase changes induced by a perturbation applied at different times of the cycle. We establish a general relationship between the robustness of key entrainment properties, such as stability and oscillator phase, on the one hand, and the shape of the PRC as characterized by a specific curvature or the existence of a dead zone, on the other hand. The criteria obtained are applied to computational models of circadian clocks and account for the disparate robustness properties of various forcing schemes. Finally, the analysis of PRCs measured experimentally in several organisms strongly suggests a case of convergent evolution toward an optimal strategy for maintaining a clock that is accurate and robust to environmental fluctuations. PMID:21641300

  5. The effects of inhaled corticosteroids on intrinsic responsiveness and histology of airways from infant monkeys exposed to house dust mite allergen and ozone

    SciTech Connect

    Joad, Jesse P. Kott, Kayleen S.; Bric, John M.; Schelegle, Edward S.; Gershwin, Laurel J.; Plopper, Charles G.; Peake, Janice L.; Pinkerton, Kent E.

    2008-01-15

    Inhaled corticosteroids (ICS) are recommended to treat infants with asthma, some with intermittent asthma. We previously showed that exposing infant monkeys to allergen/ozone resulted in asthma-like characteristics of their airways. We evaluated the effects of ICS on histology and intrinsic responsiveness of allergen/ozone-exposed and normal infant primate airways. Infant monkeys were exposed by inhalation to (1) filtered air and saline, (2) house dust mite allergen (HDMA) + ozone and saline, (3) filtered air and ICS (budesonide) or (4) HDMA + ozone and ICS. Allergen/ozone exposures started at 1 month and ICS at 3 months of age. At 6 months of age, methacholine-induced changes in luminal area of airways in proximal and distal lung slices were determined using videomicrometry, followed by histology of the same slices. Proximal airway responsiveness was increased by allergen/ozone and by ICS. Eosinophil profiles were increased by allergen/ozone in both proximal and distal airways, an effect that was decreased by ICS in distal airways. In both allergen/ozone- and air-exposed monkeys, ICS increased the number of alveolar attachments in distal airways, decreased mucin in proximal airways and decreased epithelial volume in both airways. ICS increased smooth muscle in air-exposed animals while decreasing it in allergen/ozone-exposed animals in both airways. In proximal airways, there was a small but significant positive correlation between smooth muscle and airway responsiveness, as well as between alveolar attachments and responsiveness. ICS change morphology and function in normal airways as well as allergen/ozone-exposed airways, suggesting that they should be reserved for infants with active symptoms.

  6. Electrodynamic response in the electronic nematic phase of BaFe2As2

    NASA Astrophysics Data System (ADS)

    Mirri, C.; Dusza, A.; Bastelberger, S.; Chinotti, M.; Chu, J.-H.; Kuo, H.-H.; Fisher, I. R.; Degiorgi, L.

    2016-02-01

    We perform, as a function of uniaxial stress, a temperature-dependent optical-reflectivity investigation of the parent Fe-arsenide compound BaFe2As2 over a broad spectral range, from the far infrared up to the ultraviolet, across the coincident structural tetragonal-to-orthorhombic and spin-density-wave (SDW) phase transitions at Ts ,N=135 K. Our results provide knowledge to the complete electrodynamic response of the title compound over a wide energy range as a function of both tunable variables. For temperatures below Ts ,N, varying the uniaxial stress in situ affects the twin domain population and yields hysteretic behavior of the optical properties as the stress is first increased and then decreased, whereas for temperatures above Ts ,N the stress-induced optical anisotropy is reversible, as anticipated. In particular, by analyzing the low-frequency infrared response, we obtain detailed insight to the effects determining the intrinsic anisotropy of the (metallic) charge dynamics in the orthorhombic state, and similarly the induced one due to applied uniaxial stress at higher temperatures in the tetragonal phase. The low-frequency optical conductivity thus allows establishing a link to the d c transport properties and reveals that they are determined almost exclusively by changes in the Drude weight, therefore by the anisotropy in the Fermi surface parameters. Finally, we show that the spectral weight distribution in the SDW state occurs for energies below approximately 1 eV, and therefore points towards a correlation mechanism due to Hund's coupling rather than on-site Coulomb interactions.

  7. Electrophysiological characterization of neurons in the dorsolateral pontine REM sleep induction zone of the rat: intrinsic membrane properties and responses to carbachol and orexins

    PubMed Central

    Brown§, Ritchie E.; Winston, Stuart; Basheer, Radhika; Thakkar, Mahesh M; McCarley, Robert W.

    2006-01-01

    Pharmacological, lesion and single-unit recording techniques in several animal species have identified a region of the pontine reticular formation (Subcoeruleus, SubC) just ventral to the locus coeruleus as critically involved in the generation of rapid-eye-movement (REM) sleep. However, the intrinsic membrane properties and responses of SubC neurons to neurotransmitters important in REM sleep control, such as acetylcholine and orexins/hypocretins, have not previously been examined in any animal species and thus were targeted in this study. We obtained whole-cell patch-clamp recordings from visually identified SubC neurons in rat brain slices in vitro. Two groups of large neurons (mean diameter 30 and 27μm) were tentatively identified as cholinergic (rostral SubC) and noradrenergic (caudal SubC) neurons. SubC reticular neurons (non-cholinergic, non-noradrenergic) showed a medium-sized depolarizing sag during hyperpolarizing current pulses and often had a rebound depolarization (low-threshold spike, LTS). During depolarizing current pulses they exhibited little adaptation and fired maximally at 30–90 Hz. Those SubC reticular neurons excited by carbachol (n=27) fired spontaneously at 6 Hz, often exhibited a moderately sized LTS, and varied widely in size (17–42 μm). Carbachol-inhibited SubC reticular neurons were medium-sized (15–25 μm) and constituted two groups. The larger group (n=22) was silent at rest and possessed a prominent LTS and associated 1–4 action potentials. The second, smaller group (n=8) had a delayed return to baseline at the offset of hyperpolarizing pulses. Orexins excited both carbachol excited and carbachol inhibited SubC reticular neurons. SubC reticular neurons had intrinsic membrane properties and responses to carbachol similar to those described for other reticular neurons but a larger number of carbachol inhibited neurons were found (> 50 %), the majority of which demonstrated a prominent LTS and may correspond to PGO-on neurons

  8. Performance evaluation of partial response continuous phase modulation: Discriminator detection

    NASA Astrophysics Data System (ADS)

    Trachtman, Eyal

    1989-09-01

    The principles of continuous phase modulation (CPM) are reviewed and signalling schemes based on it are discussed. The discriminator detector is widely used to detect CPM signals on band limited channels; it is a non-coherent detector which is widely used in mobile communication applications in which fading makes coherent detection difficult; it is suitable for frequency hopping systems. The detector's inferior response to that of a coherent detector can be compensated by suitable design. The performance is compared of various receivers which use the discriminator detector, using an especially written computer simulation. Receiver schemes considered included: Full response signal with integrate and dump filter; Integrate and dump filter with differential symbol detection; zero forcing linear equalization with symbol detection; Decision feedback equalization (DFE); Maximum likelihood sequence estimation; and Tomlinson filter configuration. The Tomlinson filter configuration, which has not previously been used in a CPM communication system, was compared with the other systems with respect to performance and complexity. For all CPM and detection schemes there are optimum values of h, the modulation index and there is no benefit in increasing the value of h and, therefore the bandwidth, beyond this value. Results are presented for various signal schemes, which indicate that detectability performance can be improved and bandwidth reduced by using a partial response CPM. There is a tradeoff between detectability performance and bandwidth, as a function of the baseband pulse duration. It was found that quaternary signal schemes gave better detectability performance than binary schemes, for the same bit-rates. The simulation results indicated that the Tomlinson-DFE configuration was effective for the partial response M-ary CPM channel with discriminator detection; spectral efficiency was not seriously degraded by precoding using the Tomlinson filter, and there was no

  9. Seismic Safety Margins Research Program (Phase I). Project IV. Structural building response; Structural Building Response Review

    SciTech Connect

    Healey, J.J.; Wu, S.T.; Murga, M.

    1980-02-01

    As part of the Phase I effort of the Seismic Safety Margins Research Program (SSMRP) being performed by the University of California Lawrence Livermore Laboratory for the US Nuclear Regulatory Commission, the basic objective of Subtask IV.1 (Structural Building Response Review) is to review and summarize current methods and data pertaining to seismic response calculations particularly as they relate to the objectives of the SSMRP. This material forms one component in the development of the overall computational methodology involving state of the art computations including explicit consideration of uncertainty and aimed at ultimately deriving estimates of the probability of radioactive releases due to seismic effects on nuclear power plant facilities.

  10. Ultrafast Intrinsic Photoresponse and Direct Evidence of Sub-gap States in Liquid Phase Exfoliated MoS2Thin Films

    PubMed Central

    Ghosh, Sujoy; Winchester, Andrew; Muchharla, Baleeswaraiah; Wasala, Milinda; Feng, Simin; Elias, Ana Laura; Krishna, M. Bala Murali; Harada, Takaaki; Chin, Catherine; Dani, Keshav; Kar, Swastik; Terrones, Mauricio; Talapatra, Saikat

    2015-01-01

    2-Dimensional structures with swift optical response have several technological advantages, for example they could be used as components of ultrafast light modulators, photo-detectors, and optical switches. Here we report on the fast photo switching behavior of thin films of liquid phase exfoliated MoS2, when excited with a continuous laser of λ = 658 nm (E = 1.88 eV), over a broad range of laser power. Transient photo-conductivity measurements, using an optical pump and THz probe (OPTP), reveal that photo carrier decay follows a bi-exponential time dependence, with decay times of the order of picoseconds, indicating that the photo carrier recombination occurs via trap states. The nature of variation of photocurrent with temperature confirms that the trap states are continuously distributed within the mobility gap in these thin film of MoS2, and play a vital role in influencing the overall photo response. Our findings provide a fundamental understanding of the photo-physics associated with optically active 2D materials and are crucial for developing advanced optoelectronic devices. PMID:26175112

  11. Optimal Colored Noise for Estimating Phase Response Curves

    NASA Astrophysics Data System (ADS)

    Morinaga, Kazuhiko; Miyata, Ryota; Aonishi, Toru

    2015-09-01

    The phase response curve (PRC) is an important measure representing the interaction between oscillatory elements. To understand synchrony in biological systems, many research groups have sought to measure PRCs directly from biological cells including neurons. Ermentrout et al. and Ota et al. showed that PRCs can be identified through measurement of white-noise spike-triggered averages. The disadvantage of this method is that one has to collect more than ten-thousand spikes to ensure the accuracy of the estimate. In this paper, to achieve a more accurate estimation of PRCs with a limited sample size, we use colored noise, which has recently drawn attention because of its unique effect on dynamical systems. We numerically show that there is an optimal colored noise to estimate PRCs in the most rigorous fashion.

  12. Geometric intrinsic symmetries

    SciTech Connect

    Gozdz, A. Szulerecka, A.; Pedrak, A.

    2013-08-15

    The problem of geometric symmetries in the intrinsic frame of a many-body system (nucleus) is considered. An importance of symmetrization group notion is discussed. Ageneral structure of the intrinsic symmetry group structure is determined.

  13. Interface property responsible for effective interactions of protean segments: Intrinsically disordered regions that undergo disorder-to-order transitions upon binding.

    PubMed

    Shaji, Divya; Amemiya, Takayuki; Koike, Ryotaro; Ota, Motonori

    2016-09-01

    Proteins that lack a well-defined conformation under native conditions are referred to as intrinsically disordered proteins. When interacting with partner proteins, short regions in disordered proteins can undergo disorder-to-order transitions upon binding; these regions are called protean segments (ProSs). It has been indicated that interactions of ProSs are effective: the number of contacts per residue of ProS interface is large. To reveal the properties of ProS interface that are responsible for the interaction efficiency, we classified the interface into core, rim and support, and analyzed them based on the relative accessible surface area (rASA). Despite the effective interactions, the ProS interface is mainly composed of rim residues, rather than core. The ProS rim is more effective than the rim of heterodimers, because the average rASAs of ProS rim, which is significantly large in the monomeric state, provides a large area to be used for the interactions. The amino acid composition of ProSs correlated well with those of heterodimers in both the core and rim. Therefore, the composition cannot explain why the rASAs of the ProS rim are large in the monomeric state. The balance between a small core and a large rim, and the large solvent exposure of the rim in the monomeric state, are the key to the disorder-to-order transition and the effective interactions of ProSs. PMID:27450808

  14. Shapiro Step Response of Intrinsic Josephson Junctions of (Bi1-xPbx)2Sr2CaCu2Oy at Elevated Temperatures

    NASA Astrophysics Data System (ADS)

    Oya, G.; Miyasaka, T.; Kitamura, M.; Irie, A.

    We have studied the response of stacks of intrinsic Josephson junctions (IJJs) of (Bi1-xPbx)2Sr2CaCu2Oy (x = 0.15) to injection of microwave of frequencies frf of 2-20 GHz at 4.2 K and higher temperatures. Clear constant voltage steps, which are considered Shapiro steps, are successfully observed on the current-voltage characteristic of an IJJ with a resistivity of Josephson-vortex flow Rfl in any stack under the injection of microwave. The step of the eighth order, which is the highest in this study, is observed from the largest IJJ under injection of microwave of 10 GHz at 4.2 K. But, as the temperature increases, the number of steps decreases, and finally the steps disappear at ∼45 K due to large self-heating. In this IJJ a low Rfl plays an important role in appearance of the steps of the high order. The typical behavior of the steps at 4.2 K is well reproduced by numerical simulations on that of Shapiro steps of a JJ with the shunt resistivity equal to Rfl at the temperature.

  15. Individual Patterns in Intrinsic Motivation.

    ERIC Educational Resources Information Center

    Hom, Harry L., Jr.; Maxwell, Frederick R.

    The effects of extrinsic reward on students' intrinsic interest was investigated using a single-subject design in a behavior disorders classroom. Baseline measures of the interest level of five children (ages 9-11 years) were collected for academic and non-academic tasks. Assessment was then made of each subject's response hierarchy or level of…

  16. Motexafin-Gadolinium and Involved Field Radiation Therapy for Intrinsic Pontine Glioma of Childhood: A Children's Oncology Group Phase 2 Study

    SciTech Connect

    Bradley, Kristin A.; Zhou Tianni; McNall-Knapp, Rene Y.; Jakacki, Regina I.; Pollack, Ian F.

    2013-01-01

    Purpose: To evaluate the effects on 1-year event-free survival (EFS) and overall survival (OS) of combining motexafin and gadolinium (MGd), a potent radiosensitizer, with daily fractionated radiation therapy in children with newly diagnosed intrinsic pontine gliomas. Methods and Materials: Patients with newly diagnosed intrinsic pontine glioma were treated with MGd daily for 5 consecutive days each week, for a total of 30 doses. Patients received a 5- to 10-min intravenous bolus of MGd, 4.4 mg/kg/day, given 2 to 5 h prior to standard dose irradiation. Radiation therapy was administered at a daily dose of 1.8 Gy for 30 treatments over 6 weeks. The total dose was 54 Gy. Results: Sixty eligible children received MGd daily, concurrent with 6 weeks of radiation therapy. The estimated 1-year EFS was 18% {+-} 5%, and the estimated 1-year OS was 53% {+-} 6.5%. The most common grade 3 to 4 toxicities were lymphopenia, transient elevation of liver transaminases, and hypertension. Conclusions: Compared to historical controls, the addition of MGd to a standard 6-week course of radiation did not improve the survival of pediatric patients with newly diagnosed intrinsic pontine gliomas.

  17. Ecotoxicological evaluation of low-concentration bisphenol A exposure on the soil nematode Caenorhabditis elegans and intrinsic mechanisms of stress response in vivo.

    PubMed

    Zhou, Dong; Yang, Jie; Li, Hui; Lu, Qiang; Liu, Yong-di; Lin, Kuang-Fei

    2016-08-01

    As a representative species of nematodes, Caenorhabditis elegans is an attractive animal model for evaluating ecotoxicological effects and intrinsic mechanisms of the stress response in vivo. To acquire a better knowledge of environmental effects of bisphenol A (BPA), ecotoxicological evaluations were conducted using C. elegans on the physiological (growth, locomotion behaviors, and reproduction), biochemical (lipofuscin accumulation, reactive oxygen species production, and cell apoptosis), and molecular (stress-related gene expression) responses. Nematodes were exposed to BPA (0.001-10 µM) in 2 assay systems (L4 larvae for 24 h and L1 larvae for 72 h). Exposure to BPA could significantly (p < 0.05) alter body length, locomotion behaviors, brood size, cell apoptosis, and selected stress-related gene expression. At the physiological level, BPA exerted adverse effects on nematodes at the microgram per liter level in both assay systems, with head thrashes as the most sensitive endpoint. At the biochemical level, apoptosis degree showed increases at concentrations above 0.1 µM in both assay systems. At the molecular level, BPA induced increases in selected stress-related gene expression, even at the lowest tested concentration. In addition, BPA-induced cell apoptosis was suggested as a potential mode of action, resulting in adverse physiological effects. Therefore, BPA exposure was speculated to impose developmental, reproductive, and neurobehavioral toxicities on C. elegans and caused variations of stress-related gene expression. Environ Toxicol Chem 2016;35:2041-2047. © 2016 SETAC. PMID:26748796

  18. Detecting and identifying two-dimensional symmetry-protected topological, symmetry-breaking, and intrinsic topological phases with modular matrices via tensor-network methods

    NASA Astrophysics Data System (ADS)

    Huang, Ching-Yu; Wei, Tzu-Chieh

    2016-04-01

    Symmetry-protected topological (SPT) phases exhibit nontrivial order if symmetry is respected but are adiabatically connected to the trivial product phase if symmetry is not respected. However, unlike the symmetry-breaking phase, there is no local order parameter for SPT phases. Here we employ a tensor-network method to compute the topological invariants characterized by the simulated modular S and T matrices to study transitions in a few families of two-dimensional (2D) wave functions which are ZN (N =2 and3 ) symmetric. We find that in addition to the topologically ordered phases, the modular matrices can be used to identify nontrivial SPT phases and detect transitions between different SPT phases as well as between symmetric and symmetry-breaking phases. Therefore modular matrices can be used to characterize various types of gapped phases in a unifying way.

  19. Rhodopsin and Melanopsin Contributions to the Early Redilation Phase of the Post-Illumination Pupil Response (PIPR)

    PubMed Central

    Adhikari, Prakash; Feigl, Beatrix; Zele, Andrew J.

    2016-01-01

    Melanopsin expressing intrinsically photosensitive Retinal Ganglion Cells (ipRGCs) entirely control the post-illumination pupil response (PIPR) from 6 s post-stimulus to the plateau during redilation after light offset. However, the photoreceptor contributions to the early redilation phase of the PIPR (< 6 s post-stimulus) have not been reported. Here, we evaluated the photoreceptor contributions to the early phase PIPR (0.6 s to 5.0 s) by measuring the spectral sensitivity of the criterion PIPR amplitude in response to 1 s light pulses at five narrowband stimulus wavelengths (409, 464, 508, 531 and 592 nm). The retinal irradiance producing a criterion PIPR was normalised to the peak and fitted by either a single photopigment nomogram or the combined melanopsin and rhodopsin spectral nomograms with the +L+M cone photopic luminous efficiency (Vλ) function. We show that the PIPR spectral sensitivity at times ≥ 1.7 s after light offset is best described by the melanopsin nomogram. At times < 1.7 s, the peak PIPR sensitivity shifts to longer wavelengths (range: 482 to 498 nm) and is best described by the combined photoreceptor nomogram, with major contributions from melanopsin and rhodopsin. This first report of melanopsin and rhodopsin contributions to the early phase PIPR is in line with the electrophysiological findings of ipRGC and rod signalling after the cessation of light stimuli and provides a cut-off time for isolating photoreceptor specific function in healthy and diseased eyes. PMID:27548480

  20. Self-biased magnetoelectric response in three-phase laminates

    NASA Astrophysics Data System (ADS)

    Yang, Su-Chul; Park, Chee-Sung; Cho, Kyung-Hoon; Priya, Shashank

    2010-11-01

    This study reports the experimental observation and analysis of self-biased magnetoelectric (ME) effect in three-phase laminates. The 2-2 L-T mode laminates were fabricated by attaching nickel (Ni) plates and ME particulate composite plates having 3-0 connectivity with 0.948Na0.5K0.5NbO3-0.052LiSbO3 (NKNLS) matrix and Ni0.8Zn0.2Fe2O4 (NZF) dispersant. The presence of two types of ferromagnetic materials, Ni and NZF, results in built-in magnetic bias due to difference in their magnetic susceptibilities and coercivity. This built-in bias (Hbias) provides finite ME effect at zero applied magnetic dc field. The ME response of bending mode trilayer laminate NKNLS-NZF/Ni/NKNLS-NZF in off-resonance and on-resonance conditions was shown to be mathematical combination of the trilayers with configuration NKNLS-NZF/Ni/NKNLS-NZF and NKNLS/Ni/NKNLS representing contributions from magnetic interaction and bending strain.

  1. Acute phase proteins in salmonids: evolutionary analyses and acute phase response.

    PubMed

    Jensen, L E; Hiney, M P; Shields, D C; Uhlar, C M; Lindsay, A J; Whitehead, A S

    1997-01-01

    Inflammation induces dramatic changes in the biosynthetic profile of the liver, leading to increased serum concentrations of positive acute phase (AP) proteins and decreased concentrations of negative AP proteins. Serum amyloid A (SAA) and the pentraxins C-reactive protein (CRP) and serum amyloid P component (SAP) are major AP proteins: their serum levels can rise by 1000-fold, indicating that they play a critical role in defense and/or the restoration of homeostasis. We have cloned SAA and a SAP-like pentraxin from salmonid fish species. The salmonid SAA shares approximately 70% amino acid identity with mammalian AP SAA. When salmonids are challenged with an AP stimulus, i.e., Aeromonas salmonicida, SAA responds dramatically as a major AP reactant. The salmonid pentraxin shows approximately 40% amino acid identity to both mammalian SAP and CRP. Evolutionary analysis suggests the presence of only a single such protein in teleosts and lower animal species. Surprisingly, the salmonid pentraxin behaves as a negative AP reactant, reminiscent of the SAP-like Syrian hamster female protein, in that hepatic mRNA concentrations decline to 50% of prestimulus levels. This study reinforces the hypothesis that SAA induction is an essential and universal feature of the vertebrate AP response and that it represents part of an ancient host defense system. Conversely, the species-dependent heterogeneity of pentraxin expression during the vertebrate AP response supports the possibility that its most important ancestral (and perhaps present) function is not related to its AP behavior. PMID:8977214

  2. Phase Response of Brain Alpha Wave to Temporally Alternating Red/Blue Light Emitting Diode Stimuli

    NASA Astrophysics Data System (ADS)

    Nishifuji, Seiji; Tanaka, Shogo

    2003-09-01

    Spatial phase response of the alpha wave is investigated under the condition that red and blue flicker stimuli are temporally alternately applied. The alternating stimuli lead to two distinct phase distributions depending on the subjects: 1) a phase reversal, in which the phases of the alpha waves are antilocked between the occipital and frontal regions, and 2) a quasi-phase-locking, in which the phase difference distribution includes the temporal alternation of a phase locking over the entire scalp and the phase reversal between the occiput and front. The result suggests possibilities for the underlying mechanism of the hyper-synchronization of the brain waves seen in photosensitive epilepsy.

  3. Identification of S-phase DNA damage-response targets in fission yeast reveals conservation of damage-response networks.

    PubMed

    Willis, Nicholas A; Zhou, Chunshui; Elia, Andrew E H; Murray, Johanne M; Carr, Antony M; Elledge, Stephen J; Rhind, Nicholas

    2016-06-28

    The cellular response to DNA damage during S-phase regulates a complicated network of processes, including cell-cycle progression, gene expression, DNA replication kinetics, and DNA repair. In fission yeast, this S-phase DNA damage response (DDR) is coordinated by two protein kinases: Rad3, the ortholog of mammalian ATR, and Cds1, the ortholog of mammalian Chk2. Although several critical downstream targets of Rad3 and Cds1 have been identified, most of their presumed targets are unknown, including the targets responsible for regulating replication kinetics and coordinating replication and repair. To characterize targets of the S-phase DDR, we identified proteins phosphorylated in response to methyl methanesulfonate (MMS)-induced S-phase DNA damage in wild-type, rad3∆, and cds1∆ cells by proteome-wide mass spectrometry. We found a broad range of S-phase-specific DDR targets involved in gene expression, stress response, regulation of mitosis and cytokinesis, and DNA replication and repair. These targets are highly enriched for proteins required for viability in response to MMS, indicating their biological significance. Furthermore, the regulation of these proteins is similar in fission and budding yeast, across 300 My of evolution, demonstrating a deep conservation of S-phase DDR targets and suggesting that these targets may be critical for maintaining genome stability in response to S-phase DNA damage across eukaryotes. PMID:27298342

  4. Intrinsically irreversible heat engine

    DOEpatents

    Wheatley, J.C.; Swift, G.W.; Migliori, A.

    1984-12-25

    A class of heat engines based on an intrinsically irreversible heat transfer process is disclosed. In a typical embodiment the engine comprises a compressible fluid that is cyclically compressed and expanded while at the same time being driven in reciprocal motion by a positive displacement drive means. A second thermodynamic medium is maintained in imperfect thermal contact with the fluid and bears a broken thermodynamic symmetry with respect to the fluid. The second thermodynamic medium is a structure adapted to have a low fluid flow impedance with respect to the compressible fluid, and which is further adapted to be in only moderate thermal contact with the fluid. In operation, thermal energy is pumped along the second medium due to a phase lag between the cyclical heating and cooling of the fluid and the resulting heat conduction between the fluid and the medium. In a preferred embodiment the engine comprises an acoustical drive and a housing containing a gas which is driven at a resonant frequency so as to be maintained in a standing wave. Operation of the engine at acoustic frequencies improves the power density and coefficient of performance. The second thermodynamic medium can be coupled to suitable heat exchangers to utilize the engine as a simple refrigeration device having no mechanical moving parts. Alternatively, the engine is reversible in function so as to be utilizable as a prime mover by coupling it to suitable sources and sinks of heat. 11 figs.

  5. Intrinsically irreversible heat engine

    DOEpatents

    Wheatley, J.C.; Swift, G.W.; Migliori, A.

    1984-01-01

    A class of heat engines based on an intrinsically irreversible heat transfer process is disclosed. In a typical embodiment the engine comprises a compressible fluid that is cyclically compressed and expanded while at the same time being driven in reciprocal motion by a positive displacement drive means. A second thermodynamic medium is maintained in imperfect thermal contact with the fluid and bears a broken thermodynamic symmetry with respect to the fluid. The second thermodynamic medium is a structure adapted to have a low fluid flow impedance with respect to the compressible fluid, and which is further adapted to be in only moderate thermal contact with the fluid. In operation, thermal energy is pumped along the second medium due to a phase lag between the cyclical heating and cooling of the fluid and the resulting heat conduction between the fluid and the medium. In a preferred embodiment the engine comprises an acoustical drive and a housing containing a gas which is driven at a resonant frequency so as to be maintained in a standing wave. Operation of the engine at acoustic frequencies improves the power density and coefficient of performance. The second thermodynamic medium can be coupled to suitable heat exchangers to utilize the engine as a simple refrigeration device having no mechanical moving parts. Alternatively, the engine is reversible in function so as to be utilizable as a prime mover by coupling it to suitable sources and sinks of heat.

  6. Intrinsically irreversible heat engine

    DOEpatents

    Wheatley, John C.; Swift, Gregory W.; Migliori, Albert

    1984-01-01

    A class of heat engines based on an intrinsically irreversible heat transfer process is disclosed. In a typical embodiment the engine comprises a compressible fluid that is cyclically compressed and expanded while at the same time being driven in reciprocal motion by a positive displacement drive means. A second thermodynamic medium is maintained in imperfect thermal contact with the fluid and bears a broken thermodynamic symmetry with respect to the fluid. the second thermodynamic medium is a structure adapted to have a low fluid flow impedance with respect to the compressible fluid, and which is further adapted to be in only moderate thermal contact with the fluid. In operation, thermal energy is pumped along the second medium due to a phase lag between the cyclical heating and cooling of the fluid and the resulting heat conduction between the fluid and the medium. In a preferred embodiment the engine comprises an acoustical drive and a housing containing a gas which is driven at a resonant frequency so as to be maintained in a standing wave. Operation of the engine at acoustic frequencies improves the power density and coefficient of performance. The second thermodynamic medium can be coupled to suitable heat exchangers to utilize the engine as a simple refrigeration device having no mechanical moving parts. Alternatively, the engine is reversible in function so as to be utilizable as a prime mover by coupling it to suitable sources and sinks of heat.

  7. Response of two-phase droplets to intense electromagnetic radiation

    NASA Technical Reports Server (NTRS)

    Spann, James F.; Maloney, Daniel J.; Lawson, William F.; Casleton, Kent H.

    1993-01-01

    The behavior of two-phase droplets subjected to high intensity radiation pulses is studied. Droplets are highly absorbing solids in weakly absorbing liquid medium. The objective of the study was to define heating thresholds required for causing explosive boiling and secondary atomization of the fuel droplet. The results point to mechanisms for energy storage and transport in two-phase systems.

  8. Intrinsic Control of Axon Regeneration.

    PubMed

    He, Zhigang; Jin, Yishi

    2016-05-01

    A determinant of axon regeneration is the intrinsic growth ability of injured neurons, which dictates a battery of injury responses in axons and cell bodies. While some of these regulatory mechanisms are evolutionarily conserved, others are unique to the mammalian central nervous system (CNS) where spontaneous regeneration usually does not occur. Here we examine our current understanding of these mechanisms at cellular and molecular terms and discuss their potential implications for promoting axon regeneration and functional recovery after nerve injury. PMID:27151637

  9. The dynamic response of high pressure phase of Si using phase contrast imaging and X-ray diffraction

    NASA Astrophysics Data System (ADS)

    Lee, H. J.; Galtier, E.; Xing, Z.; Gleason, A.; Granados, E.; Tavella, F.; Schropp, A.; Seiboth, F.; Schroer, C.; Higginbotham, A.; Brown, S.; Arnold, B.; Curiel, R.; Peterswright, D.; Fry, A.; Nagler, B.

    2015-11-01

    Static compression studies have revealed that crystalline silicon undergoes phase transitions from a cubic diamond structure to a variety of phases including body-centered tetragonal phase, an orthorhombic phase, and a hexagonal primitive phase. However, the dynamic response of silicon at high pressure is not well understood. Phase contrast imaging has proven to be a powerful tool for probing density changes caused by the shock propagation into a material. With respect to the elastic and plastic compression, we image shock waves in Si with high spatial resolution using the LCLS X-ray free electron laser and Matter in Extreme Conditions instrument. In this study, the long pulse optical laser with pseudoflat top shape creates high pressures up to 60 GPa. We also measure the crystal structure by observing the X-ray diffraction orthogonal to the shock propagation direction over a range of pressure. In this talk, we will present the capability of simultaneously performing phase contrast imaging and in situ X-ray diffraction during shock loading and will discuss the dynamic response of Si in high pressure phases

  10. Characterization of Recombinant Human Cytomegaloviruses Encoding IE1 Mutants L174P and 1-382 Reveals that Viral Targeting of PML Bodies Perturbs both Intrinsic and Innate Immune Responses

    PubMed Central

    Scherer, Myriam; Otto, Victoria; Stump, Joachim D.; Klingl, Stefan; Müller, Regina; Reuter, Nina; Muller, Yves A.; Sticht, Heinrich

    2015-01-01

    early protein IE1 binds to PML via a central globular domain (IE1CORE), and we have shown previously that this is sufficient to antagonize intrinsic immunity. Here, we demonstrate that modification of PML by IE1CORE not only abrogates intrinsic defense mechanisms but also attenuates the interferon response during infection. Our data show that PML plays a novel coregulatory role in type I as well as type II interferon-induced gene expression, which is antagonized by IE1CORE. Importantly, our finding supports the view that targeting of PML-NBs by viral regulatory proteins has evolved as a strategy to inhibit both intrinsic and innate immune defense mechanisms. PMID:26559840

  11. Intrinsic affinities of alkali cations for 15-crown-5 and 18-crown-6: Bond dissociation energies of gas-phase M{sup +}-crown ether complexes

    SciTech Connect

    More, M.B.; Ray, D.; Armentrout, P.B.

    1999-01-20

    Bond dissociation energies (BDEs) of M{sup +}[c-(C{sub 2}H{sub 4}O){sub 5}] and M{sup +}[c-(C{sub 2}H{sub 4}O){sub 6}] for M = Na, K, Rb, and Cs are reported. The BDEs are determined experimentally by analysis of the thresholds for collision-induced dissociation of the cation-crown ether complexes by xenon measured by using guided ion beam mass spectrometry. In all cases, the primary and lowest energy dissociation channel observed experimentally in endothermic loss of the ligand molecule. The cross section thresholds are interpreted to yield 0 and 298 K BDEs after accounting for the effects of multiple ion-molecule collisions, internal energy of the complexes, and unimolecular decay rates. For both 18-crown-6 and 15-crown-5, the BDEs decrease monotonically with increasing cation size. These results indicate that the intrinsic affinity of c-(C{sub 2}H{sub 4}O){sub 5} and c-(C{sub 2}H{sub 4}O){sub 6} for M{sup +} is determined principally by the charge density of the cation not by the ratio of the ionic radius to the cavity size. The BDEs reported here are in fair agreement with recent ab initio calculations at the MP2 level with 6-31+G* basis sets. The experimental values are systematically smaller than the computed values by 8 {+-} 2 kJ/mol per metal-oxygen interaction. The existence of less strongly bound isomers in the experimental apparatus for Rb{sup +}(15-crown-5) and Cs{sup +}(15-crown-5) appears likely, but their absence for Na{sup +} and K{sup +} complexes indicates interesting metal-dependent dynamics to the formation of such isomers.

  12. Response trajectories reveal conflict phase in image-word mismatch.

    PubMed

    van Vugt, Floris T; Cavanagh, Patrick

    2012-02-01

    In the present study, response trajectories were used in a picture–word conflict task to determine the timing of intermediate processing stages that are relatively inaccessible to response time measures. A marker was placed above or below the word ABOVE or BELOW so that its location was congruent or in conflict with the word's meaning. To report either word location(above or below the marker) or word meaning, participants moved a mouse upward toward the appropriate top left or right answer corner on the display screen.Their response trajectories showed a number of distinctive features: First, at about 200 ms after stimulus onset(the "decision moment"), the trajectory abruptly began to arc toward the appropriate answer corner; second,when the word's meaning and position were in conflict,the trajectory showed an interruption that continued until the conflict was resolved. By varying the SOA of the word and marker onsets, we found that the word meaning and word position became available at approximately 325 ms and 251 ms, respectively, after their onsets, and that the delay to resolve conflicts was about 138 ms. The timing of these response trajectory events was more stable than any extracted from the final response times, demonstrating the power of response trajectories to reveal processing stages that are only poorly resolved, if at all, by response time measures [added]. PMID:22219088

  13. [Intrinsically Photosensitive Retinal Ganglion Cells].

    PubMed

    Skorkovská, K; Skorkovská, Š

    2015-06-01

    Recently discovered intrinsically photosensitive melanopsin-containing retinal ganglion cells contribute to circadian photoentrainment and pupillary constriction; recent works have also brought new evidence for their accessory role in the visual system in humans. Pupil light reaction driven by individual photoreceptors can be isolated by means of the so called chromatic pupillography. The use of chromatic stimuli to elicit different pupillary responses may become an objective clinical pupil test in the detection of retinal diseases and in assessing new therapeutic approaches particularly in hereditary retinal degenerations like retinitis pigmentosa. In advanced stages of disease, the pupil light reaction is even more sensitive than standard electroretinography for detecting residual levels of photoreceptor activity. This review summarizes current knowledge on intrinsically photosensitive retinal cells and highlights its possible implications for clinical practice. PMID:26201360

  14. Response of an all digital phase-locked loop

    NASA Technical Reports Server (NTRS)

    Garodnick, J.; Greco, J.; Schilling, D. L.

    1974-01-01

    An all digital phase-locked loop (DPLL) is designed, analyzed, and tested. Three specific configurations are considered, generating first, second, and third order DPLL's; and it is found, using a computer simulation of a noise spike, and verified experimentally, that of these configurations the second-order system is optimum from the standpoint of threshold extension. This substantiates results obtained for analog PLL's.

  15. Theory of the spin-galvanic effect and the anomalous phase shift φ0 in superconductors and Josephson junctions with intrinsic spin-orbit coupling

    NASA Astrophysics Data System (ADS)

    Konschelle, François; Tokatly, Ilya V.; Bergeret, F. Sebastián

    2015-09-01

    Due to the spin-orbit coupling (SOC) an electric current flowing in a normal metal or semiconductor can induce a bulk magnetic moment. This effect is known as the Edelstein (EE) or magnetoelectric effect. Similarly, in a bulk superconductor a phase gradient may create a finite spin density. The inverse effect, also known as the spin-galvanic effect, corresponds to the creation of a supercurrent by an equilibrium spin polarization. Here, by exploiting the analogy between a linear-in-momentum SOC and a background SU(2) gauge field, we develop a quasiclassical transport theory to deal with magnetoelectric effects in superconducting structures. For bulk superconductors this approach allows us to easily reproduce and generalize a number of previously known results. For Josephson junctions we establish a direct connection between the inverse EE and the appearance of an anomalous phase shift φ0 in the current-phase relation. In particular we show that φ0 is proportional to the equilibrium spin current in the weak link. We also argue that our results are valid generically, beyond the particular case of linear-in-momentum SOC. The magnetoelectric effects discussed in this study may find applications in the emerging field of coherent spintronics with superconductors.

  16. Rapid and widely disseminated acute phase protein response after experimental bacterial infection of pigs

    PubMed Central

    Skovgaard, Kerstin; Mortensen, Shila; Boye, Mette; Poulsen, Karin T.; Campbell, Fiona M.; Eckersall, P. David; Heegaard, Peter M.H.

    2009-01-01

    The acute phase protein response is a well-described generalized early host response to tissue injury, inflammation and infection, observed as pronounced changes in the concentrations of a number of circulating serum proteins. The biological function of this response and its interplay with other parts of innate host defence reactions remain somewhat elusive. In order to gain new insight into this early host defence response in the context of bacterial infection we studied gene expression changes in peripheral lymphoid tissues as compared to hepatic expression changes, 14–18 h after lung infection in pigs. The lung infection was established with the pig specific respiratory pathogen Actinobacillus pleuropneumoniae. Quantitative real-time PCR based expression analysis were performed on samples from liver, tracheobronchial lymph node, tonsils, spleen and on blood leukocytes, supplemented with measurements of interleukin-6 and selected acute phase proteins in serum. C-reactive protein and serum amyloid A were clearly induced 14–18 h after infection. Extrahepatic expression of acute phase proteins was found to be dramatically altered as a result of the lung infection with an extrahepatic acute phase protein response occurring concomitantly with the hepatic response. This suggests that the acute phase protein response is a more disseminated systemic response than previously thought. The current study provides to our knowledge the first example of porcine extrahepatic expression and regulation of C-reactive protein, haptoglobin, fibrinogen, pig major acute phase protein, and transferrin in peripheral lymphoid tissues. PMID:19236838

  17. SUMO Ligase Protein Inhibitor of Activated STAT1 (PIAS1) Is a Constituent Promyelocytic Leukemia Nuclear Body Protein That Contributes to the Intrinsic Antiviral Immune Response to Herpes Simplex Virus 1

    PubMed Central

    Brown, James R.; Conn, Kristen L.; Wasson, Peter; Charman, Matthew; Tong, Lily; Grant, Kyle; McFarlane, Steven

    2016-01-01

    ABSTRACT Aspects of intrinsic antiviral immunity are mediated by promyelocytic leukemia nuclear body (PML-NB) constituent proteins. During herpesvirus infection, these antiviral proteins are independently recruited to nuclear domains that contain infecting viral genomes to cooperatively promote viral genome silencing. Central to the execution of this particular antiviral response is the small ubiquitin-like modifier (SUMO) signaling pathway. However, the participating SUMOylation enzymes are not fully characterized. We identify the SUMO ligase protein inhibitor of activated STAT1 (PIAS1) as a constituent PML-NB protein. We show that PIAS1 localizes at PML-NBs in a SUMO interaction motif (SIM)-dependent manner that requires SUMOylated or SUMOylation-competent PML. Following infection with herpes simplex virus 1 (HSV-1), PIAS1 is recruited to nuclear sites associated with viral genome entry in a SIM-dependent manner, consistent with the SIM-dependent recruitment mechanisms of other well-characterized PML-NB proteins. In contrast to that of Daxx and Sp100, however, the recruitment of PIAS1 is enhanced by PML. PIAS1 promotes the stable accumulation of SUMO1 at nuclear sites associated with HSV-1 genome entry, whereas the accumulation of other evaluated PML-NB proteins occurs independently of PIAS1. We show that PIAS1 cooperatively contributes to HSV-1 restriction through mechanisms that are additive to those of PML and cooperative with those of PIAS4. The antiviral mechanisms of PIAS1 are counteracted by ICP0, the HSV-1 SUMO-targeted ubiquitin ligase, which disrupts the recruitment of PIAS1 to nuclear domains that contain infecting HSV-1 genomes through mechanisms that do not directly result in PIAS1 degradation. IMPORTANCE Adaptive, innate, and intrinsic immunity cooperatively and efficiently restrict the propagation of viral pathogens. Intrinsic immunity mediated by constitutively expressed cellular proteins represents the first line of intracellular defense against

  18. THE ACUTE PHASE RESPONSE INDUCED BY BRONCHOSCOPY WITH LAVAGE

    EPA Science Inventory

    Bronchoscopy has been used to evaluate the inflammatory responses in vitro and in vivo. The procedure may affect acute inflammation in the lower respiratory tract. We reviewed consecutive bronchoscopies done in normal healthy non-smokers between April, 1998 and April, 2004. The...

  19. Elastic Phase Response of Silica Nanoparticles Buried in Soft Matter

    SciTech Connect

    Tetard, Laurene; Passian, Ali; Lynch, Rachel M; Voy, Brynn H; Shekhawat, Gajendra; Dravid, Vinayak; Thundat, Thomas George

    2008-01-01

    Tracking the uptake of nanomaterials by living cells is an important component in assessing both potential toxicity and in designing future materials for use in vivo. We show that the difference in the local elasticity at the site of silica (SiO{sub 2}) nanoparticles confined within a macrophage enables functional ultrasonic interactions. By elastically exciting the cell, a phase perturbation caused by the buried SiO{sub 2} nanoparticles was detected and used to map the subsurface populations of nanoparticles. Localization and mapping of stiff chemically synthesized silica nanoparticles within the cellular structures of a macrophage are important in basic as well as applied studies.

  20. Acute phase protein response in Alpine ibex with sarcoptic mange.

    PubMed

    Rahman, Md Mizanur; Lecchi, Cristina; Fraquelli, Cristina; Sartorelli, Paola; Ceciliani, Fabrizio

    2010-03-25

    The acute phase proteins (APP) are a group of serum proteins that change their concentration in animals following external or internal challenges, such as infection, inflammation or stress. The concentrations of four APPs, including serum amyloid A (SAA), haptoglobin (Hp), alpha(1)-acid glycoprotein (AGP) and ceruloplasmin (Cp) were determined in serum collected from healthy Alpine ibexes (Capra ibex) and ibexes with Sarcoptes scabiei mange. Primary structures of all four APPs were determined by cDNA sequencing. The concentrations of all four APPs were higher in serum of animals with clinical signs of sarcoptic mange when compared to healthy animals. Two of the APPs, including SAA and AGP, acted as major APPs, since their serum concentrations were increased more than 10-folds when compared to healthy animals (P<0.001). The other two APPs, including Hp and Cp, acted as minor acute phase proteins, as their concentrations were increased from two to five folds (P<0.001). These findings provide a remarkable potential as diagnostic markers for the early detection of sarcoptic mange in free ranging animals. PMID:20036058

  1. Lipolytic and metabolic response to glucagon in fasting king penguins: phase II vs. phase III.

    PubMed

    Bernard, Servane F; Thil, Marie-Anne; Groscolas, Rene

    2003-02-01

    This study aims to determine how glucagon intervenes in the regulation of fuel metabolism, especially lipolysis, at two stages of a spontaneous long-term fast characterized by marked differences in lipid and protein availability and/or utilization (phases II and III). Changes in the plasma concentration of various metabolites and hormones, and in lipolytic fluxes as determined by continuous infusion of [2-3H]glycerol and [1-14C]palmitate, were examined in vivo in a subantarctic bird (king penguin) before, during, and after a 2-h glucagon infusion. In the two fasting phases, glucagon infusion at a rate of 0.025 microg. kg(-1). min(-1) induced a three- to fourfold increase in the plasma concentration and in the rate of appearance (Ra) of glycerol and nonesterified fatty acids, the percentage of primary reesterification remaining unchanged. Infusion of glucagon also resulted in a progressive elevation of the plasma concentration of glucose and beta-hydroxybutyrate and in a twofold higher insulinemia. These changes were not significantly different between the two phases. The plasma concentrations of triacylglycerols and uric acid were unaffected by glucagon infusion, except for a 40% increase in plasma uric acid in phase II birds. Altogether, these results indicate that glucagon in a long-term fasting bird is highly lipolytic, hyperglycemic, ketogenic, and insulinogenic, these effects, however, being similar in phases II and III. The maintenance of the sensitivity of adipose tissue lipolysis to glucagon could suggest that the major role of the increase in basal glucagonemia observed in phase III is to stimulate gluconeogenesis rather than fatty acid delivery. PMID:12388477

  2. Fluid phase recognition molecules in neutrophil-dependent immune responses.

    PubMed

    Jaillon, Sébastien; Ponzetta, Andrea; Magrini, Elena; Barajon, Isabella; Barbagallo, Marialuisa; Garlanda, Cecilia; Mantovani, Alberto

    2016-04-01

    The innate immune system comprises both a cellular and a humoral arm. Neutrophils are key effector cells of the immune and inflammatory responses and have emerged as a major source of humoral pattern recognition molecules (PRMs). These molecules, which include collectins, ficolins, and pentraxins, are specialised in the discrimination of self versus non-self and modified-self and share basic multifunctional properties including recognition and opsonisation of pathogens and apoptotic cells, activation and regulation of the complement cascade and tuning of inflammation. Neutrophils act as a reservoir of ready-made soluble PRMs, such as the long pentraxin PTX3, the peptidoglycan recognition protein PGRP-S, properdin and M-ficolin, which are stored in neutrophil granules and are involved in neutrophil effector functions. In addition, other soluble PRMs, such as members of the collectin family, are not expressed in neutrophils but can modulate neutrophil-dependent immune responses. Therefore, soluble PRMs are an essential part of the innate immune response and retain antibody-like effector functions. Here, we will review the expression and general function of soluble PRMs, focusing our attention on molecules involved in neutrophil effector functions. PMID:27021644

  3. Acute-phase response factor, a nuclear factor binding to acute-phase response elements, is rapidly activated by interleukin-6 at the posttranslational level.

    PubMed Central

    Wegenka, U M; Buschmann, J; Lütticken, C; Heinrich, P C; Horn, F

    1993-01-01

    Interleukin-6 (IL-6) is known to be a major mediator of the acute-phase response in liver. We show here that IL-6 triggers the rapid activation of a nuclear factor, termed acute-phase response factor (APRF), both in rat liver in vivo and in human hepatoma (HepG2) cells in vitro. APRF bound to IL-6 response elements in the 5'-flanking regions of various acute-phase protein genes (e.g., the alpha 2-macroglobulin, fibrinogen, and alpha 1-acid glycoprotein genes). These elements contain a characteristic hexanucleotide motif, CTGGGA, known to be required for the IL-6 responsiveness of these genes. Analysis of the binding specificity of APRF revealed that it is different from NF-IL6 and NF-kappa B, transcription factors known to be regulated by cytokines and involved in the transcriptional regulation of acute-phase protein genes. In HepG2 cells, activation of APRF was observed within minutes after stimulation with IL-6 or leukemia-inhibitory factor and did not require ongoing protein synthesis. Therefore, a preexisting inactive form of APRF is activated by a posttranslational mechanism. We present evidence that this activation occurs in the cytoplasm and that a phosphorylation is involved. These results lead to the conclusions that APRF is an immediate target of the IL-6 signalling cascade and is likely to play a central role in the transcriptional regulation of many IL-6-induced genes. Images PMID:7678052

  4. A pilot study of phase-evoked acoustic responses from the ears of human subjects

    NASA Astrophysics Data System (ADS)

    Christensen, Anders T.; Dewey, James; Dhar, Sumitrajit; Ordoñez, Rodrigo; Hammershøi, Dorte

    2015-12-01

    Otoacoustic emissions (OAEs) evoked by pure tones lock onto the phase of the stimulus at the place of their generation in the cochlea. The effects of phase transitions in a pure tone stimulus on OAEs have not been investigated. By combining responses to pure tones with smooth phase transitions, phase-evoked residual responses (PERRs) were extracted from nine normal-hearing subjects. Five of them had PERRs in at least 18 of 36 parameter conditions expected to yield a response. PERRs do not have a straightforward dependence on stimulus parameters, but their general prevalence suggests a temporary decoupling between stimulus and OAE phase - between 5 and 10 ms. Since the stimulus is narrow in the frequency domain, the PERR may reflect the dynamic behavior of localized regions of OAE generators.

  5. Multimodal Responses of Self-Organized Circuitry in Electronically Phase Separated Materials

    DOE PAGESBeta

    Herklotz, Andreas; Guo, Hangwen; Wong, Anthony T.; Lee, Ho Nyung; Rack, Philip D.; Ward, Thomas Z.

    2016-07-13

    When confining an electronically phase we separated manganite film to the scale of its coexisting self-organized metallic and these insulating domains allows resistor-capacitor circuit-like responses while providing both electroresistive and magnetoresistive switching functionality.

  6. An ATM-independent S-phase checkpoint response involves CHK1 pathway

    NASA Technical Reports Server (NTRS)

    Zhou, Xiang-Yang; Wang, Xiang; Hu, Baocheng; Guan, Jun; Iliakis, George; Wang, Ya

    2002-01-01

    After exposure to genotoxic stress, proliferating cells actively slow down the DNA replication through a S-phase checkpoint to provide time for repair. We report that in addition to the ataxia-telangiectasia mutated (ATM)-dependent pathway that controls the fast response, there is an ATM-independent pathway that controls the slow response to regulate the S-phase checkpoint after ionizing radiation in mammalian cells. The slow response of S-phase checkpoint, which is resistant to wortmannin, sensitive to caffeine and UCN-01, and related to cyclin-dependent kinase phosphorylation, is much stronger in CHK1 overexpressed cells, and it could be abolished by Chk1 antisense oligonucleotides. These results provide evidence that the ATM-independent slow response of S-phase checkpoint involves CHK1 pathway.

  7. The frequency response of phased-array antennas

    NASA Astrophysics Data System (ADS)

    Brock, B. C.

    1989-02-01

    The phased-array antenna will be examined from the point of view of effects caused by changes in frequency. Both simple linear arrays and the more complex conformal array are examined. For the conformal array, a comparison between a corporate-feed structure and a row series-feed structure is included. There are two primary effects which will be discussed: beam-pointing errors and distortion of large bandwidth signals. A formula for estimating the operating or tunable array bandwidth for narrow-bandwidth signals is derived. An expression for the wide-bandwidth-signal transfer function is also obtained and examined. It will be shown that the transfer function depends both on the array scan angle and the position within the mainbeam.

  8. The frequency response of phased-array antennas

    SciTech Connect

    Brock, B.C.

    1989-02-01

    The phased-array antenna will be examined from the point of view of effects caused by changes in frequency. Both simple linear arrays and the more complex conformal array are examined. For the conformal array, a comparison between a corporate-feed structure and a row series-feed structure is included. There are two primary effects which will be discussed: beam-pointing errors and distortion of large bandwidth signals. A formula for estimating the operating or tunable array bandwidth for narrow-bandwidth signals is derived. An expression for the wide-bandwidth-signal transfer function is also obtained and examined. It will be shown that the transfer function depends both on the array scan angle and the position within the mainbeam. 25 figs.

  9. Atomic-Scale Determination of Active Facets on the MoVTeNb Oxide M1 Phase and Their Intrinsic Catalytic Activity for Ethane Oxidative Dehydrogenation.

    PubMed

    Melzer, Daniel; Xu, Pinghong; Hartmann, Daniela; Zhu, Yuanyuan; Browning, Nigel D; Sanchez-Sanchez, Maricruz; Lercher, Johannes A

    2016-07-25

    Aberration-corrected high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) has been used to image the basal {001} plane of the catalytically relevant M1 phase in MoVTeNb complex oxides. Facets {010}, {120}, and {210} are identified as the most frequent lateral termination planes of the crystals. Combination of STEM with He ion microscopy (HIM) images, Rietveld analysis, and kinetic tests reveals that the activation of ethane is correlated to the availability of facets {001}, {120}, and {210} at the surface of M1 crystals. The lateral facets {120} and {210} expose crystalline positions related to the typical active centers described for propane oxidation. Conversely, the low activity of the facet {010} is attributed to its configuration, consisting of only stable M6 O21 units connected by a single octahedron. Thus, we quantitatively demonstrated that differences in catalytic activity among M1 samples of equal chemical composition depend primarily on the morphology of the particles, which determines the predominant terminating facets. PMID:26990594

  10. Intrinsic time quantum geometrodynamics

    NASA Astrophysics Data System (ADS)

    Ita, Eyo Eyo; Soo, Chopin; Yu, Hoi-Lai

    2015-08-01

    Quantum geometrodynamics with intrinsic time development and momentric variables is presented. An underlying SU(3) group structure at each spatial point regulates the theory. The intrinsic time behavior of the theory is analyzed, together with its ground state and primordial quantum fluctuations. Cotton-York potential dominates at early times when the universe was small; the ground state naturally resolves Penrose's Weyl curvature hypothesis, and thermodynamic and gravitational "arrows of time" point in the same direction. Ricci scalar potential corresponding to Einstein's general relativity emerges as a zero-point energy contribution. A new set of fundamental commutation relations without Planck's constant emerges from the unification of gravitation and quantum mechanics.

  11. Intrinsic structure in Saturn's rings

    NASA Astrophysics Data System (ADS)

    Albers, N.

    2015-10-01

    Saturn's rings are the most prominent in our Solar system and one example of granular matter in space. Dominated by tides and inelastic collisions the system is highly flattened being almost 300000km wide while only tens of meters thick. Individual particles are composed of primarily water ice and range from microns to few tens of meters in size. Apparent patterns comprise ringlets, gaps, kinematic wakes, propellers, bending waves, and the winding spiral arms of density waves. These large-scale structures are perturbations foremost created by external as well as embedded moons. Observations made by the Cassini spacecraft currently in orbit around Saturn show these structures in unprecedented detail. But high-resolution measurements reveal the presence of small-scale structures throughout the system. These include self-gravity wakes (50-100m), overstable waves (100-300m), subkm structure at the A and B ring edges, "straw" and "ropy" structures (1-3km), and the C ring "ghosts". Most of these had not been anticipated and are found in perturbed regions, driven by resonances with external moons, where the system undergoes periodic phases of compression and relaxation that correlate with the presence of structure. High velocity dispersion and the presence of large clumps imply structure formation on time scales as short as one orbit (about 10 hours). The presence of these intrinsic structures is seemingly the response to varying local conditions such as internal density, optical depth, underlying particle size distribution, granular temperature, and distance from the central planet. Their abundance provides evidence for an active and dynamic ring system where aggregation and fragmentation are ongoing on orbital timescales. Thus a kinetic description of the rings may be more appropriate than the fluid one. I will present Cassini Ultraviolet Spectrometer (UVIS) High Speed Photometer (HSP) occultations, Voyager 1 and 2 Imaging Science Subsystem (ISS), and high

  12. Effect of menstrual cycle phase on the ventilatory response to rising body temperature during exercise.

    PubMed

    Hayashi, Keiji; Kawashima, Takayo; Suzuki, Yuichi

    2012-07-01

    To examine the effect of menstrual cycle on the ventilatory sensitivity to rising body temperature, ten healthy women exercised for ~60 min on a cycle ergometer at 50% of peak oxygen uptake during the follicular and luteal phases of their cycle. Esophageal temperature, mean skin temperature, mean body temperature, minute ventilation, and tidal volume were all significantly higher at baseline and during exercise in the luteal phase than the follicular phase. On the other hand, end-tidal partial pressure of carbon dioxide was significantly lower during exercise in the luteal phase than the follicular phase. Plotting ventilatory parameters against esophageal temperature revealed there to be no significant menstrual cycle-related differences in the slopes or intercepts of the regression lines, although minute ventilation and tidal volume did significantly differ during exercise with mild hyperthermia. To evaluate the cutaneous vasodilatory response, relative laser-Doppler flowmetry values were plotted against mean body temperature, which revealed that the mean body temperature threshold for cutaneous vasodilation was significantly higher in the luteal phase than the follicular phase, but there were no significant differences in the sensitivity or peak values. These results suggest that the menstrual cycle phase influences the cutaneous vasodilatory response during exercise and the ventilatory response at rest and during exercise with mild hyperthermia, but it does not influence ventilatory responses during exercise with moderate hyperthermia. PMID:22604882

  13. Phase I and Phase II Objective Response Rates are Correlated in Pediatric Cancer Trials: An Argument for Better Clinical Trial Efficiency.

    PubMed

    Yeh, Jonathan C; Huang, Peng; Cohen, Kenneth J

    2016-07-01

    Although many phase I trials report tumor response, formal analysis of efficacy is deferred to phase II. We reviewed paired phase I and II pediatric oncology trials to ascertain the relationship between phase I and II objective response rate (OR%). Single-agent phase I trials were paired with corresponding phase II trials (comparable study drug, dosing schedule, and population). Phase I trials without efficacy data or a matching phase II trial were excluded. OR% was tabulated for all trials, and phase II authors' subjective conclusions regarding efficacy were documented; 35 pairs of trials were analyzed. The correlation between phase I and II OR% was 0.93. Between phase II studies with a "positive" conclusion versus a "negative" one, there was a statistically significant difference in mean phase I OR% (32.0% vs. 4.5%, P<0.001). Thirteen phase II studies were undertaken despite phase I OR% of 0%; only 1 had a "positive" conclusion, and none exceeded OR% of 15%. OR% are highly correlated between phase I and II pediatric oncology trials. Although not a formal measure of drug efficacy, phase I OR% may provide an estimate of phase II response, inform phase II study design, and should be given greater consideration. PMID:27164535

  14. Diminished acute phase response and increased hepatic inflammation of aged rats in response to intraperitoneal injection of lipopolysaccharide.

    PubMed

    Gomez, Christian R; Acuña-Castillo, Claudio; Pérez, Claudio; Leiva-Salcedo, Elías; Riquelme, Denise M; Ordenes, Gamaliel; Oshima, Kiyoko; Aravena, Mauricio; Pérez, Viviana I; Nishimura, Sumiyo; Sabaj, Valeria; Walter, Robin; Sierra, Felipe

    2008-12-01

    Aging is associated with a deterioration of the acute phase response to inflammatory challenges. However, the nature of these defects remains poorly defined. We analyzed the hepatic inflammatory response after intraperitoneal administration of lipopolysaccharide (LPS) given to Fisher 344 rats aged 6, 15, and 22-23 months. Induction of the acute phase proteins (APPs), haptoglobin, alpha-1-acid glycoprotein, and T-kininogen was reduced and/or retarded with aging. Initial induction of interleukin-6 in aged rats was normal, but the later response was increased relative to younger counterparts. An exacerbated hepatic injury was observed in aged rats receiving LPS, as evidenced by the presence of multiple microabscesses in portal tracts, confluent necrosis, higher neutrophil accumulation, and elevated serum levels of alanine aminotransferase, relative to younger animals. Our results suggest that aged rats displayed a reduced expression of APPs and increased hepatic injury in response to the inflammatory insult. PMID:19126842

  15. Titanosilicates with Strong Phase-Matched Second Harmonic Generation Responses.

    PubMed

    Chao, Tzu-Ling; Chang, Wen-Jung; Wen, Shu-Han; Lin, Yu-Qing; Chang, Bor-Chen; Lii, Kwang-Hwa

    2016-07-27

    The search for new and efficient nonlinear optical (NLO) materials has been an active research because of their technological importance in laser applications. Although a large number of frequency-doubling oxides, phosphates, borates, and fluoride-containing borates were found, no transition-metal silicate with useful NLO properties has been reported. We have now synthesized and grown crystals of two new titanosilicates, Li2K4[(TiO)Si4O12] and Li2Rb4[(TiO)Si4O12], by using a flux and supercritical hydrothermal method. Their unique 3D framework structures contain highly compressed TiO5 square pyramids which are arranged one over the other to form infinite ···Ti-O···Ti-O straight chains with alternating short and long Ti-O distances. These two materials meet the requirements for efficient second harmonic generation including lack of center of inversion symmetry, large susceptibility, phase matching, transmitting at wavelengths of interest, resistant to laser damage, and thermally stable. These attributes make them very attractive for frequency-doubling materials. PMID:27416357

  16. Origins of asymmetric stress-strain response in phase transformations

    SciTech Connect

    Sehitoglu, H.; Gall, K.

    1997-12-31

    It has been determined that the transformation stress-strain behavior of CuZnAl and NiTi shape memory alloys is dependent on the applied stress state. The uniaxial compressive stress necessary to macroscopically trigger the transformation is approximately 34% (CuZnAl) and 26% (NiTi) larger than the required uniaxial tensile stress. For three dimensional stress states, the response of either alloy system is dependent on the directions of the dominant principal stresses along with the hydrostatic stress component of the stress state. The stress state effects are dominated by the favored growth and nucleation of more martensite plates in tension versus compression. The effect of different hydrostatic pressure levels between stress states on martensite plates volume change is considered small.

  17. Dissociable Roles of Right Inferior Frontal Cortex and Anterior Insula in Inhibitory Control: Evidence from Intrinsic and Task-Related Functional Parcellation, Connectivity, and Response Profile Analyses across Multiple Datasets

    PubMed Central

    Ryali, Srikanth; Chen, Tianwen; Li, Chiang-Shan R.

    2014-01-01

    The right inferior frontal cortex (rIFC) and the right anterior insula (rAI) have been implicated consistently in inhibitory control, but their differential roles are poorly understood. Here we use multiple quantitative techniques to dissociate the functional organization and roles of the rAI and rIFC. We first conducted a meta-analysis of 70 published inhibitory control studies to generate a commonly activated right fronto-opercular cortex volume of interest (VOI). We then segmented this VOI using two types of features: (1) intrinsic brain activity; and (2) stop-signal task-evoked hemodynamic response profiles. In both cases, segmentation algorithms identified two stable and distinct clusters encompassing the rAI and rIFC. The rAI and rIFC clusters exhibited several distinct functional characteristics. First, the rAI showed stronger intrinsic and task-evoked functional connectivity with the anterior cingulate cortex, whereas the rIFC had stronger intrinsic and task-evoked functional connectivity with dorsomedial prefrontal and lateral fronto-parietal cortices. Second, the rAI showed greater activation than the rIFC during Unsuccessful, but not Successful, Stop trials, and multivoxel response profiles in the rAI, but not the rIFC, accurately differentiated between Successful and Unsuccessful Stop trials. Third, activation in the rIFC, but not rAI, predicted individual differences in inhibitory control abilities. Crucially, these findings were replicated in two independent cohorts of human participants. Together, our findings provide novel quantitative evidence for the dissociable roles of the rAI and rIFC in inhibitory control. We suggest that the rAI is particularly important for detecting behaviorally salient events, whereas the rIFC is more involved in implementing inhibitory control. PMID:25355218

  18. Predicting Intrinsic Motivation

    ERIC Educational Resources Information Center

    Martens, Rob; Kirschner, Paul A.

    2004-01-01

    Intrinsic motivation can be predicted from participants' perceptions of the social environment and the task environment (Ryan & Deci, 2000)in terms of control, relatedness and competence. To determine the degree of independence of these factors 251 students in higher vocational education (physiotherapy and hotel management) indicated the extent to…

  19. A low-pH-inducible, stationary-phase acid tolerance response in Salmonella typhimurium.

    PubMed Central

    Lee, I S; Slonczewski, J L; Foster, J W

    1994-01-01

    Acid is an important environmental condition encountered by Salmonella typhimurium during its pathogenesis. Our studies have shown that the organism can actively adapt to survive potentially lethal acid exposures by way of at least three possibly overlapping systems. The first is a two-stage system induced in response to low pH by logarithmic-phase cells called the log-phase acid tolerance response (ATR). It involves a major molecular realignment of the cell including the induction of over 40 proteins. The present data reveal that two additional systems of acid resistance occur in stationary-phase cells. One is a pH-dependent system distinct from log-phase ATR called stationary-phase ATR. It was shown to provide a higher level of acid resistance than log-phase ATR but involved the synthesis of fewer proteins. Maximum induction of stationary-phase ATR occurred at pH 4.3. A third system of acid resistance is not induced by low pH but appears to be part of a general stress resistance induced by stationary phase. This last system requires the alternative sigma factor, RpoS. Regulation of log-phase ATR and stationary-phase ATR remains RpoS independent. Although the three systems are for the most part distinct from each other, together they afford maximum acid resistance for S. typhimurium. Images PMID:8113183

  20. Microsecond linear optical response in the unusual nematic phase of achiral bimesogens

    NASA Astrophysics Data System (ADS)

    Panov, V. P.; Balachandran, R.; Nagaraj, M.; Vij, J. K.; Tamba, M. G.; Kohlmeier, A.; Mehl, G. H.

    2011-12-01

    Some hydrocarbon linked mesogenic dimers are known to exhibit an additional nematic phase (Nx) below a conventional uniaxial nematic (Nu) phase. Although composed of non-chiral molecules, the Nx phase is found to exhibit linear (polar) switching under applied electric field. This switching has remarkably low response time of the order of a few microseconds. Two chiral domains with opposite handedness and consequently opposite responses are found in planar cells. Uniformly lying helix, electroclinic, and flexoelectric effects are given as possible causes for this intriguing phenomenon.

  1. Angus and Romosinuano steers exhibit differential acute phase responses following an endotoxin challenge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our primary objective was to elucidate the acute phase response in cattle while evaluating potential genetic differences between two diverse Bos taurus breeds [Angus (AG) and Romosinuano (RO)] in response to an endotoxin challenge. The Romosinuano is a tropically adapted Bos taurus breed developed i...

  2. Neuro-oscillatory phase alignment drives speeded multisensory response times: an electro-corticographic investigation.

    PubMed

    Mercier, Manuel R; Molholm, Sophie; Fiebelkorn, Ian C; Butler, John S; Schwartz, Theodore H; Foxe, John J

    2015-06-01

    Even simple tasks rely on information exchange between functionally distinct and often relatively distant neuronal ensembles. Considerable work indicates oscillatory synchronization through phase alignment is a major agent of inter-regional communication. In the brain, different oscillatory phases correspond to low- and high-excitability states. Optimally aligned phases (or high-excitability states) promote inter-regional communication. Studies have also shown that sensory stimulation can modulate or reset the phase of ongoing cortical oscillations. For example, auditory stimuli can reset the phase of oscillations in visual cortex, influencing processing of a simultaneous visual stimulus. Such cross-regional phase reset represents a candidate mechanism for aligning oscillatory phase for inter-regional communication. Here, we explored the role of local and inter-regional phase alignment in driving a well established behavioral correlate of multisensory integration: the redundant target effect (RTE), which refers to the fact that responses to multisensory inputs are substantially faster than to unisensory stimuli. In a speeded detection task, human epileptic patients (N = 3) responded to unisensory (auditory or visual) and multisensory (audiovisual) stimuli with a button press, while electrocorticography was recorded over auditory and motor regions. Visual stimulation significantly modulated auditory activity via phase reset in the delta and theta bands. During the period between stimulation and subsequent motor response, transient synchronization between auditory and motor regions was observed. Phase synchrony to multisensory inputs was faster than to unisensory stimulation. This sensorimotor phase alignment correlated with behavior such that stronger synchrony was associated with faster responses, linking the commonly observed RTE with phase alignment across a sensorimotor network. PMID:26041921

  3. The additional loss of Bak and not the lack of the protein tyrosine kinase p56/Lck in one JCaM1.6 subclone caused pronounced apoptosis resistance in response to stimuli of the intrinsic pathway.

    PubMed

    Rudner, J; Mueller, A-C; Matzner, N; Huber, S M; Handrick, R; Belka, C; Jendrossek, V

    2009-05-01

    Ionising radiation, hypoxia, and the cyclooxygenase-2 inhibitor Celecoxib are known agonists of the intrinsic apoptosis pathway that involves mitochondrial damage upstream of caspase activation. Mitochondrial integrity is regulated by the pro-apoptotic Bcl-2 protein family members Bak and Bax. Upstream of the mitochondria, many kinases and phosphatases control the apoptotic response. However, the role of the non-receptor tyrosine kinase p56/Lck during apoptosis is controversial. The present investigation demonstrate the existence of two JCaM1.6 subclones, one expressing and one deficient for Bak. The lack of p56/Lck expression in JCaM1.6 cells per se did hardly affect apoptosis induced by ionising radiation, hypoxia, or Celecoxib. Only the additional loss of Bak expression, as observed in one JCaM1.6 subclone, rendered the cells resistant. siRNA-mediated downregulation of Bak and p56/Lck mimicked the observed effects in the subclones. Earlier experiments performed with the Bak-negative clone might have lead to the wrong assumption that lack of p56/Lck alone, and not the additonal loss of Bak, was responsible for reduced sensitivity towards stimuli of the intrinsic apoptosis pathway. PMID:19343496

  4. Subjective, Physiological, and Cognitive Responses to Intravenous Nicotine: Effects of Sex and Menstrual Cycle Phase

    PubMed Central

    DeVito, Elise E; Herman, Aryeh I; Waters, Andrew J; Valentine, Gerald W; Sofuoglu, Mehmet

    2014-01-01

    Nicotine dependence is a serious public health concern. Optimal treatment of nicotine dependence will require greater understanding of the mechanisms that contribute to the maintenance of smoking behaviors. A growing literature indicates sex and menstrual phase differences in responses to nicotine. The aim of this study was to assess sex and menstrual phase influences on a broad range of measures of nicotine response including subjective drug effects, cognition, physiological responses, and symptoms of withdrawal, craving, and affect. Using a well-established intravenous nicotine paradigm and biochemical confirmation of overnight abstinence and menstrual cycle phase, analyses were performed to compare sex (age 18–50 years; 115 male and 45 female) and menstrual cycle phase (29 follicular and 16 luteal) effects. Females had diminished subjective drug effects of, but greater physiological responses to, nicotine administration. Luteal-phase females showed diminished subjective drug effects and better cognition relative to follicular-phase women. These findings offer candidate mechanisms through which the luteal phase, wherein progesterone is dominant relative to estradiol, may be protective against vulnerability to smoking. PMID:24345818

  5. Acute phase response induced following tumor treatment by photodynamic therapy: relevance for the therapy outcome

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen; Merchant, Soroush; Stott, Brandon; Cecic, Ivana; Payne, Peter; Sun, Jinghai

    2006-02-01

    Acute phase response is an effector process orchestrated by the innate immune system for the optimal mobilization of the resources of the organism distant from the local insult site needed in the execution of a host-protecting reaction. Our research has shown that mice bearing tumors treated by photodynamic therapy (PDT) exhibit the three major hallmarks of acute phase response: release of acute phase reactants, neutrophilia, and pituitary/adrenal axis activation. Of particular interest in this study were acute phase proteins that have a pivotal role in the clearance of dead cells, since the occurrence of this process in PDT-treated tumors emerges as a critical event in the course of PDT-associated host response. It is shown that this type of acute phase reactants, including complement proteins (C3, C5, C9, mannose-binding lectin, and ficolin A) and related pentraxins (serum amyloid P component and PTX3), are upregulated following tumor PDT and accumulate in the targeted lesions. Based on the recently accumulated experimental evidence it is definitely established that the acute phase response is manifested in the hosts bearing PDT-treated tumors and it is becoming clear that this effector process is an important element of PDT-associated host response bearing in impact on the eventual outcome of this therapy.

  6. Natural twilight phase-response curves for the cave-dwelling bat, Hipposideros speoris.

    PubMed

    Vanlalnghaka, C; Keny, V L; Satralkar, M K; Khare, P V; Pujari, P D; Joshi, D S

    2005-01-01

    Phase-response curves (PRCs) for the circadian rhythm of flight activity of the microchiropteran bat (Hipposideros speoris) were determined in a cave, employing discrete natural dawn and dusk twilight pulses. These PRCs are reported for the first time for any circadian system and they are unlike other PRCs constructed for nocturnal mammals. Dawn and dusk twilight pulses evoked advance and delay phase shifts, respectively. Advance phase shifts were followed by 3 to 4 advancing transients and a subsequent shortening of free-running period (tau); whereas, the delay phase shifts were instantaneous without any transients but with a subsequent lengthening of tau. PMID:16298767

  7. Experimental evidence of the theoretical spatial frequency response of cubic phase mask wavefront coding imaging systems.

    PubMed

    Somayaji, Manjunath; Bhakta, Vikrant R; Christensen, Marc P

    2012-01-16

    The optical transfer function of a cubic phase mask wavefront coding imaging system is experimentally measured across the entire range of defocus values encompassing the system's functional limits. The results are compared against mathematical expressions describing the spatial frequency response of these computational imagers. Experimental data shows that the observed modulation and phase transfer functions, available spatial frequency bandwidth and design range of this imaging system strongly agree with previously published mathematical analyses. An imaging system characterization application is also presented wherein it is shown that the phase transfer function is more robust than the modulation transfer function in estimating the strength of the cubic phase mask. PMID:22274533

  8. Effects of low-spatial-frequency response of phase plates on TEM imaging

    NASA Astrophysics Data System (ADS)

    Edgcombe, C. J.

    2015-10-01

    Images of simple objects produced by a perfect lens and a phase plate have been calculated by use of Abbe theory for Foucault, Hilbert and Zernike phase plates. The results show that with a Zernike plate, white outlines and ringing like those observed previously can be caused by the beam hole, which limits the low-spatial-frequency response of the system even when the lens behaves perfectly. When the change of phase added by the phase plate is distributed over a range of radius rather than a simple step, the unwanted effects are substantially reduced.

  9. The effects of digitizing rate and phase distortion errors on the shock response spectrum

    NASA Technical Reports Server (NTRS)

    Wise, J. H.

    1983-01-01

    Some of the methods used for acquisition and digitization of high-frequency transients in the analysis of pyrotechnic events, such as explosive bolts for spacecraft separation, are discussed with respect to the reduction of errors in the computed shock response spectrum. Equations are given for maximum error as a function of the sampling rate, phase distortion, and slew rate, and the effects of the characteristics of the filter used are analyzed. A filter is noted to exhibit good passband amplitude, phase response, and response to a step function is a compromise between the flat passband of the elliptic filter and the phase response of the Bessel filter; it is suggested that it be used with a sampling rate of 10f (5 percent).

  10. Oltipraz-induced phase 2 enzyme response conserved in cells lacking mitochondrial DNA.

    PubMed

    Chua, Yee Liu; Zhang, Dawei; Boelsterli, Urs; Moore, Philip K; Whiteman, Matthew; Armstrong, Jeffrey S

    2005-11-11

    Oltipraz, a member of a class of 1,2-dithiolethiones, is a potent phase 2 enzyme inducing agent used as a cancer chemopreventive. In this study, we investigated regulation of the phase 2 enzyme response and protection against endogenous oxidative stress in lymphoblastic leukemic parental CEM cells and cells lacking mitochondrial DNA (mtDNA) (rho0) by oltipraz. Glutathione (GSH) levels (total and mitochondrial) and glutathione S-transferase (GST) activity were significantly increased after pretreatment with oltipraz in both parental (rho+) and rho0 cells, and both cell lines were resistant to mitochondrial oxidation, loss of mitochondrial membrane potential, and cell death in response to the GSH depleting agent diethylmaleate. These results show that the phase 2 enzyme response, by enhancing GSH-dependent systems involved in xenobiotic metabolism, blocks endogenous oxidative stress and cell death, and that this response is intact in cells lacking mtDNA. PMID:16188238

  11. Survival of Campylobacter jejuni during Stationary Phase: Evidence for the Absence of a Phenotypic Stationary-Phase Response

    PubMed Central

    Kelly, Alison F.; Park, Simon F.; Bovill, Richard; Mackey, Bernard M.

    2001-01-01

    When Campylobacter jejuni NCTC 11351 was grown microaerobically in rich medium at 39°C, entry into stationary phase was followed by a rapid decline in viable numbers to leave a residual population of 1% of the maximum number or less. Loss of viability was preceded by sublethal injury, which was seen as a loss of the ability to grow on media containing 0.1% sodium deoxycholate or 1% sodium chloride. Resistance of cells to mild heat stress (50°C) or aeration was greatest in exponential phase and declined during early stationary phase. These results show that C. jejuni does not mount the normal phenotypic stationary-phase response which results in enhanced stress resistance. This conclusion is consistent with the absence of rpoS homologues in the recently reported genome sequence of this species and their probable absence from strain NCTC 11351. During prolonged incubation of C. jejuni NCTC 11351 in stationary phase, an unusual pattern of decreasing and increasing heat resistance was observed that coincided with fluctuations in the viable count. During stationary phase of Campylobacter coli UA585, nonmotile variants and those with impaired ability to form coccoid cells were isolated at high frequency. Taken together, these observations suggest that stationary-phase cultures of campylobacters are dynamic populations and that this may be a strategy to promote survival in at least some strains. Investigation of two spontaneously arising variants (NM3 and SC4) of C. coli UA585 showed that a reduced ability to form coccoid cells did not affect survival under nongrowth conditions. PMID:11319108

  12. Liquid demixing of intrinsically disordered proteins is seeded by poly(ADP-ribose)

    PubMed Central

    Altmeyer, Matthias; Neelsen, Kai J.; Teloni, Federico; Pozdnyakova, Irina; Pellegrino, Stefania; Grøfte, Merete; Rask, Maj-Britt Druedahl; Streicher, Werner; Jungmichel, Stephanie; Nielsen, Michael Lund; Lukas, Jiri

    2015-01-01

    Intrinsically disordered proteins can phase separate from the soluble intracellular space, and tend to aggregate under pathological conditions. The physiological functions and molecular triggers of liquid demixing by phase separation are not well understood. Here we show in vitro and in vivo that the nucleic acid-mimicking biopolymer poly(ADP-ribose) (PAR) nucleates intracellular liquid demixing. PAR levels are markedly induced at sites of DNA damage, and we provide evidence that PAR-seeded liquid demixing results in rapid, yet transient and fully reversible assembly of various intrinsically disordered proteins at DNA break sites. Demixing, which relies on electrostatic interactions between positively charged RGG repeats and negatively charged PAR, is amplified by aggregation-prone prion-like domains, and orchestrates the earliest cellular responses to DNA breakage. We propose that PAR-seeded liquid demixing is a general mechanism to dynamically reorganize the soluble nuclear space with implications for pathological protein aggregation caused by derailed phase separation. PMID:26286827

  13. Observation of spectrum effect on the measurement of intrinsic error field on EAST

    NASA Astrophysics Data System (ADS)

    Wang, Hui-Hui; Sun, You-Wen; Qian, Jin-Ping; Shi, Tong-Hui; Shen, Biao; Gu, Shuai; Liu, Yue-Qiang; Guo, Wen-Feng; Chu, Nan; He, Kai-Yang; Jia, Man-Ni; Chen, Da-Long; Xue, Min-Min; Ren, Jie; Wang, Yong; Sheng, Zhi-Cai; Xiao, Bing-Jia; Luo, Zheng-Ping; Liu, Yong; Liu, Hai-Qing; Zhao, Hai-Lin; Zeng, Long; Gong, Xian-Zu; Liang, Yun-Feng; Wan, Bao-Nian; The EAST Team

    2016-06-01

    Intrinsic error field on EAST is measured using the ‘compass scan’ technique with different n  =  1 magnetic perturbation coil configurations in ohmically heated discharges. The intrinsic error field measured using a non-resonant dominated spectrum with even connection of the upper and lower resonant magnetic perturbation coils is of the order {{b}r2,1}/{{B}\\text{T}}≃ {{10}-5} and the toroidal phase of intrinsic error field is around {{60}{^\\circ}} . A clear difference between the results using the two coil configurations, resonant and non-resonant dominated spectra, is observed. The ‘resonant’ and ‘non-resonant’ terminology is based on vacuum modeling. The penetration thresholds of the non-resonant dominated cases are much smaller than that of the resonant cases. The difference of penetration thresholds between the resonant and non-resonant cases is reduced by plasma response modeling using the MARS-F code.

  14. Sulfur antisite-induced intrinsic high-temperature ferromagnetism in Ag2S:Y nanocrystals.

    PubMed

    Wang, Pan; Yang, Tianye; Zhao, Rui; Zhang, Mingzhe

    2016-04-21

    There is an urgent need for a complete understanding of intrinsic ferromagnetism, due to the necessity for application of ferromagnetic semiconductors. Here, further insight into the magnetic mechanism of sulfur antisite-induced intrinsic high-temperature ferromagnetism is investigated in Ag2S:Y nanocrystals. The gas-liquid phase chemical deposition method is adopted to obtain the monoclinic Ag2S:Y nanocrystals. The field and temperature-dependent magnetization measurements demonstrate the robust high-temperature ferromagnetism of Ag2S:Y nanocrystals. As revealed in the magnetic origin study from first-principles calculations, the intrinsic sulfur antisite defect is only responsible for the creation of a magnetic moment which mainly comes from the S 3p and Ag 4d orbitals. Such a mechanism, which is essentially different from those of dopants and other native defects, provides new insight into the origin of the magnetism. PMID:27009760

  15. Tailoring Vacancies Far Beyond Intrinsic Levels Changes the Carrier Type and Optical Response in Monolayer MoSe 2−x Crystals

    DOE PAGESBeta

    Mahjouri-Samani, Masoud; Liang, Liangbo; Oyedele, Akinola; Kim, Yong-Sung; Tian, Mengkun; Cross, Nicholas; Wang, Kai; Lin, Ming-Wei; Boulesbaa, Abdelaziz; Rouleau, Christopher M.; et al

    2016-07-14

    Defect engineering has been a critical step in controlling the transport characteristics of electronic devices, and the ability to create, tune, and annihilate defects is essential to enable the range of next-generation devices. Whereas defect formation has been well-demonstrated in three-dimensional semiconductors, similar exploration of the heterogeneity in atomically thin two-dimensional semiconductors and the link between their atomic structures, defects, and properties has not yet been extensively studied. In this paper, we demonstrate the growth of MoSe2–x single crystals with selenium (Se) vacancies far beyond intrinsic levels, up to ~20%, that exhibit a remarkable transition in electrical transport properties frommore » n- to p-type character with increasing Se vacancy concentration. A new defect-activated phonon band at ~250 cm-1 appears, and the A1g Raman characteristic mode at 240 cm-1 softens toward ~230 cm-1 which serves as a fingerprint of vacancy concentration in the crystals. We show that post-selenization using pulsed laser evaporated Se atoms can repair Se-vacant sites to nearly recover the properties of the pristine crystals. Finally, first-principles calculations reveal the underlying mechanisms for the corresponding vacancy-induced electrical and optical transitions.« less

  16. Tailoring Vacancies Far Beyond Intrinsic Levels Changes the Carrier Type and Optical Response in Monolayer MoSe2-x Crystals.

    PubMed

    Mahjouri-Samani, Masoud; Liang, Liangbo; Oyedele, Akinola; Kim, Yong-Sung; Tian, Mengkun; Cross, Nicholas; Wang, Kai; Lin, Ming-Wei; Boulesbaa, Abdelaziz; Rouleau, Christopher M; Puretzky, Alexander A; Xiao, Kai; Yoon, Mina; Eres, Gyula; Duscher, Gerd; Sumpter, Bobby G; Geohegan, David B

    2016-08-10

    Defect engineering has been a critical step in controlling the transport characteristics of electronic devices, and the ability to create, tune, and annihilate defects is essential to enable the range of next-generation devices. Whereas defect formation has been well-demonstrated in three-dimensional semiconductors, similar exploration of the heterogeneity in atomically thin two-dimensional semiconductors and the link between their atomic structures, defects, and properties has not yet been extensively studied. Here, we demonstrate the growth of MoSe2-x single crystals with selenium (Se) vacancies far beyond intrinsic levels, up to ∼20%, that exhibit a remarkable transition in electrical transport properties from n- to p-type character with increasing Se vacancy concentration. A new defect-activated phonon band at ∼250 cm(-1) appears, and the A1g Raman characteristic mode at 240 cm(-1) softens toward ∼230 cm(-1) which serves as a fingerprint of vacancy concentration in the crystals. We show that post-selenization using pulsed laser evaporated Se atoms can repair Se-vacant sites to nearly recover the properties of the pristine crystals. First-principles calculations reveal the underlying mechanisms for the corresponding vacancy-induced electrical and optical transitions. PMID:27416103

  17. Ab Initio Infrared Spectra and Electronic Response Calculations for the Insulating Phases of VO2

    NASA Astrophysics Data System (ADS)

    Hendriks, Christopher; Huffman, Tyler; Walter, Eric; Qazilbash, Mumtaz; Krakauer, Henry

    Previous studies have shown that, under doping or tensile strain and upon heating, the well-known vanadium dioxide (VO2) transition from an insulating monoclinic (M1) to a metallic rutile (R) phase progresses through a triclinic symmetry (T) phase and a magnetic monoclinic phase (M2), both of which are insulating. Structurally, this progression from M1 to R through T and M2 can be characterized by the progressive breaking of the V dimers. Investigation of the effect of these structural changes on the insulating phases of VO2 may help resolve questions surrounding the long-debated issue of the respective roles of electronic correlation and Peierls mechanisms in driving the MIT. We investigated electronic and vibrational properties of the insulating phases of VO2 in the framework of DFT+U. We will present ab initio calculations of infrared spectra and optical electronic responses for the insulating phases and compare these to available experimental measurements. Supported by ONR.

  18. Enhanced response to ozone exposure during the follicular phase of the menstrual cycle

    SciTech Connect

    Fox, S.D.; Adams, W.C.; Brookes, K.A.; Lasley, B.L. )

    1993-08-01

    Exposure to ozone (O[sub 3]), a toxic component of photochemical smog, results in significant airway inflammation, respiratory discomfort, and pulmonary function impairment. These effects can be reduced via pretreatment with anti-inflammatory agents. Progesterone, a gonadal steroid, is known to reduce general inflammation in the uterine endometrium. However, it is not known whether fluctuation in blood levels of progesterone, which are experienced during the normal female menstrual cycle, could alter O[sub 3] inflammatory-induced pulmonary responses. In this study, we tested the hypothesis that young, adult females are more responsive to O[sub 3] inhalation with respect to pulmonary function impairment during their follicular (F) menstrual phase when progesterone levels are lowest that during their mid-luteal (ML) phase when progesterone levels are highest. Nine subjects with normal ovarian function were exposed in random order for 1 hour each to filtered air and to 0.30 ppm O[sub 3] in their F and ML menstrual phases. Ozone responsiveness was measured by percent change in pulmonary function from pre- to postexposure. Significant gas concentration effects (filtered air versus O[sub 3]) were observed for forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV[sub 1]), and forced expiratory flow between 25 and 75% of FVC (FEF[sub 25-75]), showed a significant menstrual phase and gas concentration interaction effect, with larger decrements observed in the F menstrual phase when progesterone concentrations were significantly lower. We conclude that young, adult females appear to be more responsive to acute O[sub 3] exposure during the F phase than during the ML phase of their menstrual cycles. This difference in pulmonary function response could be related to the anti-inflammatory effects of increased progesterone concentrations during the luteal phase.

  19. Hypercapnic blood pressure response is greater during the luteal phase of the menstrual cycle.

    PubMed

    Edwards, N; Wilcox, I; Polo, O J; Sullivan, C E

    1996-11-01

    We investigated the cardiovascular responses to acute hypercapnia during the menstrual cycle. Eleven female subjects with regular menstrual cycles performed hypercapnic rebreathing tests during the follicular and luteal phases of their menstrual cycles. Ventilatory and cardiovascular variables were recorded breath by breath. Serum progesterone and estradiol were measured on each occasion. Serum progesterone was higher during the luteal [50.4 +/- 9.6 (SE) nmol/l] than during the follicular phase (2.1 +/- 0.7 nmol/l; P < 0.001), but serum estradiol did not differ (follicular phase, 324 +/- 101 pmol/l; luteal phase, 162 +/- 71 pmol/l; P = 0.61). The systolic blood pressure responses during hypercapnia were 2.0 +/- 0.3 and 4.0 +/- 0.5 mmHg/Torr (1 Torr = 1 mmHg rise in end-tidal PCO2) during the follicular and luteal phases, respectively, of the menstrual cycle (P < 0.01). The diastolic blood pressure responses were 1.1 +/- 0.2 and 2.1 +/- 0.3 mmHg/Torr during the follicular and luteal phases, respectively (P < 0.002). Heart rate responses did not differ during the luteal (1.7 +/- 0.3 beats.min-1.Torr-1) and follicular phases (1.4 +/- 0.3 beats.min-1.Torr-1; P = 0.59). These data demonstrate a greater pressor response during the luteal phase of the menstrual cycle that may be related to higher serum progesterone concentrations. PMID:8941539

  20. Intrinsic gas-phase reactivity of ionized 6-(oxomethylene)cyclohexa-2,4-dienone: evidence pointing to its neutral alpha-oxoketene counterpart as a proper precursor of various benzopyran-4-ones and analogues.

    PubMed

    de Carvalho, Paulo Sergio; Nachtigall, Fabiane M; Eberlin, Marcos Nogueira; Moraes, Luiz Alberto Beraldo

    2007-08-01

    Despite its unique structure and potential use as an important building block in organic synthesis, the title alpha-oxoketene 1 has been formed mostly under very special conditions as a short-lived species. The reactivity of 1 is, therefore, nearly unexplored. In great contrast, it seemed that its ionized gaseous form 1*+ is stable and easily accessible. In this study, we used multiple-stage pentaquadrupole mass spectrometry to probe the formation of gaseous 1*+ and explore its stability and intrinsic reactivity. With water and methanol, gaseous 1*+ was found to react similarly to solvated 1, which indicates that there is a close parallel between their reactivities. Gaseous 1*+ was also found to react promptly via polar [3 + 2] cycloadditons with various dienophiles including alkenes, alkynes, isocyanates, ketones and esters, thus forming a series of benzopyran-4-ones (flavones, 4-chromanones, 4-chromenones, benzo[1,3]dioxin-4-ones, and analogues) that are common structural units in many natural products. The present availability of 1 at room temperature and the gas-phase findings reported herein for gaseous 1*+ indicate that solvated 1 should undergo many [4 + 2] cycloadditions and functions as a versatile precursor of a variety of biologically active molecules. PMID:17629330

  1. Associations between adrenocortical activity and nicotine response in female smokers by menstrual phase.

    PubMed

    Huttlin, Eileen A; Allen, Alicia M; Tosun, Nicole L; Allen, Sharon S; al'Absi, Mustafa

    2015-11-01

    Previous research suggests that menstrual phase may influence smoking-related symptomatology. The present study analyzes the relationship between menstrual phase and salivary cortisol with subjective responses to nicotine among female smokers during ad libitum smoking. We hypothesize higher cortisol levels would be associated with increased positive and decreased negative subjective responses to nicotine. We also expected that these associations would vary by menstrual phase. Females aged 18-40 who smoke at least five cigarettes/day, reported regular menstrual cycles and did not use exogenous hormones or psychotropic medications were enrolled into a controlled cross-over trial. Participants completed identical data collection procedures during follicular (F) and luteal (L) phases; including self-collected salivary cortisol samples and completion of a nicotine response lab session involving administration of nicotine nasal spray and monitoring of subjective response to nicotine via the Subjective State Scale and Visual Analog Scale. Participants (n = 116) were 29.1 ± 6.9 years old and smoked an average of 12.3 ± 5.5 cigarettes daily. During F phase, higher morning cortisol was associated with decreased negative affect (r = -0.21, p = 0.03), withdrawal (r = -0.30, p < 0.01) and increased relaxation (r = 0.24, p = 0.02) after administration of nicotine nasal spray. Conversely, during L phase, higher morning cortisol was associated with a decrease in head rush (r = -0.26, p = 0.01) and urge to smoke (r = -0.21, p = 0.04) after administration of nicotine nasal spray. Similar associations between greater diurnal cortisol variation and response to nicotine were seen. These observations indicate that cortisol may have a phase-specific association with some subjective responses to nicotine in female smokers. Additional research should explore how these relationships may influence smoking cessation efforts. PMID:26135333

  2. Intraday Variability: Intrinsic or Extrinsic?

    NASA Astrophysics Data System (ADS)

    Sarma Kuchibhotla, Huthavahana; Lister, Matthew; Homan, Dan; Kellermann, Ken; Aller, Hugh; Aller, Margo; Agudo, Ivan; Arshakian, Tigran; Kovalev, Yuri; Lobanov, Andrew; Pushkarev, Alexander; Ros, Eduardo; Savolainen, Tuomas; Zensus, Tony; Kadler, Matthias; Vermeulen, Rene; Gehrels, Neil; McEnery, Julie; Sambruna, Rita; Tueller, Jack; Cohen, Marshall; Hovatta, Talvikki; Kharb, Preeti; Cooper, Nathan; Hogan, Brandon; Cara, Mihai

    A significant fraction of flat spectrum AGN exhibit rapid variability both in total intensity as well as polarization at cm wavelengths, on time scales ranging from a few hours to a few days, a phenomenon termed Intra Day Variability (IDV). The physical process responsible for this behavior is not well understood, though various models ranging from source-intrinsic (e.g., shock-in-jet) to source-extrinsic (e.g., scintillation due to electron density fl uctuations in the interstellar medium) have been proposed. The absence of multi-epoch data (especially at 2 cm) further exacerbates the situation. We present the results of analysis of archival VLBA data for a flux density limited sample of bright, flat spectrum AGN located predominantly in the north-ern sky, collected under the MOJAVE program. We find a clear detection of IDV in 25% of the 365 sources analyzed. We find significant differences in the IDV properties of quasars and true BL Lacs. Intermediate BL Lac objects, so classified due to the presence of broad lines in their optical spectra, have IDV characteristics similar to those of quasars. As expected, the presum-able weakly beamed CSS/GPS sources show no IDV. We find IDV properties to be correlated with source intrinsic properties such as Brightness temperature/Doppler factor and apparent speed. Episodes of IDV activity associated with radio flaring and/or component ejection have also been observed, suggesting an intrinsic mechanism at work. However, we also find IDV to be strongly correlated with the galactic latitude position of the source, indicative of a scintil-lation mechanism. However, we find no correlation between IDV and the observing day of the year, IDV and redshift of the source. We propose a qualitative model to explain all these results. The program is supported under the NSF grant 080786-AST and NASA grant NNX08AV67G.

  3. A phase response curve to single bright light pulses in human subjects

    NASA Technical Reports Server (NTRS)

    Khalsa, Sat Bir S.; Jewett, Megan E.; Cajochen, Christian; Czeisler, Charles A.

    2003-01-01

    The circadian pacemaker is differentially sensitive to the resetting effects of retinal light exposure, depending upon the circadian phase at which the light exposure occurs. Previously reported human phase response curves (PRCs) to single bright light exposures have employed small sample sizes, and were often based on relatively imprecise estimates of circadian phase and phase resetting. In the present study, 21 healthy, entrained subjects underwent pre- and post-stimulus constant routines (CRs) in dim light (approximately 2-7 lx) with maintained wakefulness in a semi-recumbent posture. The 6.7 h bright light exposure stimulus consisted of alternating 6 min fixed gaze (approximately 10 000 lx) and free gaze (approximately 5000-9000 lx) exposures. Light exposures were scheduled across the circadian cycle in different subjects so as to derive a PRC. Plasma melatonin was used to determine the phase of the onset, offset, and midpoint of the melatonin profiles during the CRs. Phase shifts were calculated as the difference in phase between the pre- and post-stimulus CRs. The resultant PRC of the midpoint of the melatonin rhythm revealed a characteristic type 1 PRC with a significant peak-to-trough amplitude of 5.02 h. Phase delays occurred when the light stimulus was centred prior to the critical phase at the core body temperature minimum, phase advances occurred when the light stimulus was centred after the critical phase, and no phase shift occurred at the critical phase. During the subjective day, no prolonged 'dead zone' of photic insensitivity was apparent. Phase shifts derived using the melatonin onsets showed larger magnitudes than those derived from the melatonin offsets. These data provide a comprehensive characterization of the human PRC under highly controlled laboratory conditions.

  4. The adaptation of a reflex response to the ongoing phase of locomotion in fish.

    PubMed

    Grillner, S; Rossignol, S; Wallén, P

    1977-10-24

    The reflex response to stimulation of the tail fin has been studied in the swimming fish, by bilateral electromyographical (EMG) recordings in several segments along the body. The response varies with the phase of swimming. When the muscles on one side (segment) are active, a large response will occur on this side but no response on the contralateral side at the same level. When the other side becomes active an identical stimulus will cause an activation of this side but no response on the previously active side. When the movements were filmed a powerful mechanical effect was demonstrated with an augmentation of the ongoing movement, that would result in an instantaneous increase in speed. The stimulus causes in addition a shortening of the duration of the swimming cycle and its components. Most of the results were obtained on spinal dogfish, which also exhibits spontaneous locomotion after a spinal transection. Mainly electrical bipolar stimulation of the tail fin was used. Identical stimuli applied in different phases on an ongoing movement, thus give a reflex response that changes dramatically with the phase of the movement. This phase dependent reflex reversal is functionally meaningful; it is fast and due to spinal mechanisms. PMID:590408

  5. Controlling the nonlinear optical properties of plasmonic nanoparticles with the phase of their linear response.

    PubMed

    Butet, Jérémy; Raziman, T V; Yang, Kuang-Yu; Bernasconi, Gabriel D; Martin, Olivier J F

    2016-07-25

    We numerically investigate the second harmonic generation from different plasmonic systems and evidence the key role played in their nonlinear response by the phase at the fundamental wavelength. In the case of a single plasmonic nanorod, the interference between the second harmonic dipolar and quadrupolar emission modes depends on their relative phase, which is deeply related to the excitation wavelength. The knowledge obtained in this simple case is then used to describe and understand the nonlinear response from a more complex structure, namely a gold nanodolmen. The complex phase evolution associated with a Fano resonance arising at the fundamental wavelength enables dramatically modifying the second harmonic emission patterns from plasmonic metamolecules within minute wavelength shifts. These results emphasize the importance of the phase in the nonlinear optical processes arising in plasmonic nanostructures, in addition to the increase in conversion yield associated with the excitation of localized surface plasmon resonances. PMID:27464164

  6. Intrinsic and extrinsic mortality reunited.

    PubMed

    Koopman, Jacob J E; Wensink, Maarten J; Rozing, Maarten P; van Bodegom, David; Westendorp, Rudi G J

    2015-07-01

    Intrinsic and extrinsic mortality are often separated in order to understand and measure aging. Intrinsic mortality is assumed to be a result of aging and to increase over age, whereas extrinsic mortality is assumed to be a result of environmental hazards and be constant over age. However, allegedly intrinsic and extrinsic mortality have an exponentially increasing age pattern in common. Theories of aging assert that a combination of intrinsic and extrinsic stressors underlies the increasing risk of death. Epidemiological and biological data support that the control of intrinsic as well as extrinsic stressors can alleviate the aging process. We argue that aging and death can be better explained by the interaction of intrinsic and extrinsic stressors than by classifying mortality itself as being either intrinsic or extrinsic. Recognition of the tight interaction between intrinsic and extrinsic stressors in the causation of aging leads to the recognition that aging is not inevitable, but malleable through the environment. PMID:25916736

  7. Clinical Practice Guideline for the Treatment of Intrinsic Circadian Rhythm Sleep-Wake Disorders: Advanced Sleep-Wake Phase Disorder (ASWPD), Delayed Sleep-Wake Phase Disorder (DSWPD), Non-24-Hour Sleep-Wake Rhythm Disorder (N24SWD), and Irregular Sleep-Wake Rhythm Disorder (ISWRD). An Update for 2015

    PubMed Central

    Auger, R. Robert; Burgess, Helen J.; Emens, Jonathan S.; Deriy, Ludmila V.; Thomas, Sherene M.; Sharkey, Katherine M.

    2015-01-01

    A systematic literature review and meta-analyses (where appropriate) were performed and the GRADE approach was used to update the previous American Academy of Sleep Medicine Practice Parameters on the treatment of intrinsic circadian rhythm sleep-wake disorders. Available data allowed for positive endorsement (at a second-tier degree of confidence) of strategically timed melatonin (for the treatment of DSWPD, blind adults with N24SWD, and children/ adolescents with ISWRD and comorbid neurological disorders), and light therapy with or without accompanying behavioral interventions (adults with ASWPD, children/adolescents with DSWPD, and elderly with dementia). Recommendations against the use of melatonin and discrete sleep-promoting medications are provided for demented elderly patients, at a second- and first-tier degree of confidence, respectively. No recommendations were provided for remaining treatments/ populations, due to either insufficient or absent data. Areas where further research is needed are discussed. Citation: Auger RR, Burgess HJ, Emens JS, Deriy LV, Thomas SM, Sharkey KM. Clinical practice guideline for the treatment of intrinsic circadian rhythm sleep-wake disorders: advanced sleep-wake phase disorder (ASWPD), delayed sleep-wake phase disorder (DSWPD), non-24-hour sleep-wake rhythm disorder (N24SWD), and irregular sleep-wake rhythm disorder (ISWRD). An update for 2015. J Clin Sleep Med 2015;11(10):1199–1236. PMID:26414986

  8. Ultrafast terahertz-induced response of GeSbTe phase-change materials

    SciTech Connect

    Shu, Michael J.; Zalden, Peter; Chen, Frank; Weems, Ben; Chatzakis, Ioannis; Xiong, Feng; Jeyasingh, Rakesh; Pop, Eric; Philip Wong, H.-S.; Hoffmann, Matthias C.; Wuttig, Matthias; Lindenberg, Aaron M.

    2014-06-23

    The time-resolved ultrafast electric field-driven response of crystalline and amorphous GeSbTe films has been measured all-optically, pumping with single-cycle terahertz pulses as a means of biasing phase-change materials on a sub-picosecond time-scale. Utilizing the near-band-gap transmission as a probe of the electronic and structural response below the switching threshold, we observe a field-induced heating of the carrier system and resolve the picosecond-time-scale energy relaxation processes and their dependence on the sample annealing condition in the crystalline phase. In the amorphous phase, an instantaneous electroabsorption response is observed, quadratic in the terahertz field, followed by field-driven lattice heating, with Ohmic behavior up to 200 kV/cm.

  9. Evidence that venoconstriction reverses the phase II sympathoinhibitory and bradycardic response to haemorrhage.

    PubMed

    Potas, J R; Dampney, R A L

    2004-03-31

    Severe hypotensive haemorrhage results in a biphasic response, characterized by an initial increase in heart rate and sympathetic vasomotor activity (phase I) followed by a life-threatening hypotension, accompanied by profound sympathoinhibition and bradycardia (phase II). The phase II response is believed to be dependent on inputs from cardiopulmonary receptors, and may be triggered by the reduction in venous return and cardiac filling associated with severe haemorrhage. In this study, we tested the hypothesis that the phase II response could be reversed by venoconstriction, which is known to enhance venous return and cardiac filling, by comparing the effects of phenylephrine (which constricts veins as well as arterioles) with that of vasopressin (which constricts arterioles but not veins). In sodium pentobarbitone-anaesthetised rats, haemorrhage evoked an initial increase in heart rate (HR) and renal sympathetic activity (RSNA) followed by a large decrease in both variables to levels below the pre-haemorrhage baseline levels (phase II response). During the phase II response, an intravenous injection of phenylephrine, sufficient to restore mean arterial pressure to the pre-haemorrhage level, resulted in a gradually developing increase (over 3-4 min) in HR and RSNA back to the baseline levels. In contrast, intravenous injection of an equipressor dose of vasopressin did not result in any increase in RSNA and only a transient increase in HR. Injection of phenylephrine, but not vasopressin, also increased the pulsatile component of central venous pressure, indicative of reduced venous capacitance. The findings indicate that venoconstriction reverses the phase II sympathoinhibition and bradycardia. PMID:15109933

  10. Discrimination of Speech Stimuli Based on Neuronal Response Phase Patterns Depends on Acoustics But Not Comprehension

    PubMed Central

    Poeppel, David

    2010-01-01

    Speech stimuli give rise to neural activity in the listener that can be observed as waveforms using magnetoencephalography. Although waveforms vary greatly from trial to trial due to activity unrelated to the stimulus, it has been demonstrated that spoken sentences can be discriminated based on theta-band (3–7 Hz) phase patterns in single-trial response waveforms. Furthermore, manipulations of the speech signal envelope and fine structure that reduced intelligibility were found to produce correlated reductions in discrimination performance, suggesting a relationship between theta-band phase patterns and speech comprehension. This study investigates the nature of this relationship, hypothesizing that theta-band phase patterns primarily reflect cortical processing of low-frequency (<40 Hz) modulations present in the acoustic signal and required for intelligibility, rather than processing exclusively related to comprehension (e.g., lexical, syntactic, semantic). Using stimuli that are quite similar to normal spoken sentences in terms of low-frequency modulation characteristics but are unintelligible (i.e., their time-inverted counterparts), we find that discrimination performance based on theta-band phase patterns is equal for both types of stimuli. Consistent with earlier findings, we also observe that whereas theta-band phase patterns differ across stimuli, power patterns do not. We use a simulation model of the single-trial response to spoken sentence stimuli to demonstrate that phase-locked responses to low-frequency modulations of the acoustic signal can account not only for the phase but also for the power results. The simulation offers insight into the interpretation of the empirical results with respect to phase-resetting and power-enhancement models of the evoked response. PMID:20484530

  11. Intrinsic and Extrinsic Motivation among Collegiate Instrumentalists

    ERIC Educational Resources Information Center

    Diaz, Frank M.

    2010-01-01

    The purpose of this study was to gather and compare information on measures of intrinsic and extrinsic motivation among instrumentalists enrolled in collegiate ensembles. A survey instrument was developed to gather information concerning demographic data and responses to questions on motivational preference. Participants were undergraduate and…

  12. Post-traumatic inflammatory response: perhaps a succession of phases with a nutritional purpose.

    PubMed

    Aller, Maria-Angeles; Arias, Jorge-Luis; Arias, Jaime

    2004-01-01

    Post-traumatic inflammatory response, whether this be local or systemic, is considered to be the succession of three functional phases called nervous, immune and endocrine, that could have a nutritional significance. In the nervous phase, ischemia-reperfusion, which causes interstitial and cellular edema, is produced. Both types of edema could represent an ancestral mechanism to feed the cells by diffusion. During the immune phase, the tissues are infiltrated by inflammatory cells and bacteria. Then, extracellular digestion, by enzyme release (fermentation), and intracellular digestion by phagocytosis could be associated with a hypothetical trophic capacity for the neighbouring cells. Finally, in the late or endocrine phase nutrition mediated by the blood capillaries is established. In these three successive phases the inflammatory response goes on from an anaerobic metabolism (ischemia) through a metabolism characterized by a defective oxygen use (reperfusion, oxidative burst and heat hyperproduction) to an oxidative metabolism (oxidative phosphorilation) with a correct use of oxygen to produce usable energy. This type of metabolism is characterized by a large production of ATP, which is used to drive specialized multiple cellular processes. Since the nervous, immune and endocrine phases of the inflammatory response go from ischemia to the development of an oxidative metabolism, It is also tempting to speculate on whether the body reproduces the successive stages by which life passes from its origin without oxygen until it develops an effective, although costly, system for the use of oxygen every time we suffer post-traumatic acute inflammation. PMID:15193345

  13. Phase Synchronization and Desynchronization of Structural Response Induced by Turbulent and External Sound

    NASA Technical Reports Server (NTRS)

    Maestrello, Lucio

    2002-01-01

    Acoustic and turbulent boundary layer flow loadings over a flexible structure are used to study the spatial-temporal dynamics of the response of the structure. The stability of the spatial synchronization and desynchronization by an active external force is investigated with an array of coupled transducers on the structure. In the synchronous state, the structural phase is locked, which leads to the formation of spatial patterns while the amplitude peaks exhibit chaotic behaviors. Large amplitude, spatially symmetric loading is superimposed on broadband, but in the desynchronized state, the spectrum broadens and the phase space is lost. The resulting pattern bears a striking resemblance to phase turbulence. The transition is achieved by using a low power external actuator to trigger broadband behaviors from the knowledge of the external acoustic load inducing synchronization. The changes are made favorably and efficiently to alter the frequency distribution of power, not the total power level. Before synchronization effects are seen, the panel response to the turbulent boundary layer loading is discontinuously spatio-temporally correlated. The stability develops from different competing wavelengths; the spatial scale is significantly shorter than when forced with the superimposed external sound. When the external sound level decreases and the synchronized phases are lost, changes in the character of the spectra can be linked to the occurrence of spatial phase transition. These changes can develop broadband response. Synchronized responses of fuselage structure panels have been observed in subsonic and supersonic aircraft; results from two flights tests are discussed.

  14. Increased vasopressin and adrenocorticotropin responses to stress in the midluteal phase of the menstrual cycle.

    PubMed

    Altemus, M; Roca, C; Galliven, E; Romanos, C; Deuster, P

    2001-06-01

    Accumulating evidence indicates that gonadal steroids modulate functioning of the hypothalamic-pituitary-adrenal (HPA) axis, which has been closely linked to the pathophysiology of anxiety and depression. However, the effect of the natural menstrual cycle on HPA axis responsivity to stress has not been clearly described. In nine healthy women, metabolic and hormonal responses to treadmill exercise stress during the early follicular phase of the menstrual cycle, when gonadal steroid levels are low, were compared with responses in the midluteal phase of the cycle, when both progesterone and estrogen levels are relatively high. Exercise intensity was gradually increased over 20 min to reach 90% of each subject's maximal oxygen consumption during the final 5 min of exercise. Basal plasma lactate, glucose, ACTH, vasopressin, oxytocin, and cortisol levels were similar in the two cycle phases. However, in response to exercise stress, women in the midluteal phase had enhanced ACTH (P < 0.0001), vasopressin (P < 0.01), and glucose (P < 0.001) secretion. These findings suggest that relatively low levels of gonadal steroids during the early follicular phase of the menstrual cycle provide protection from the impact of stress on the HPA axis. PMID:11397850

  15. Optimal phase response curves for stochastic synchronization of limit-cycle oscillators by common Poisson noise

    NASA Astrophysics Data System (ADS)

    Hata, Shigefumi; Arai, Kensuke; Galán, Roberto F.; Nakao, Hiroya

    2011-07-01

    We consider optimization of phase response curves for stochastic synchronization of noninteracting limit-cycle oscillators by common Poisson impulsive signals. The optimal functional shape for sufficiently weak signals is sinusoidal, but can differ for stronger signals. By solving the Euler-Lagrange equation associated with the minimization of the Lyapunov exponent characterizing synchronization efficiency, the optimal phase response curve is obtained. We show that the optimal shape mutates from a sinusoid to a sawtooth as the constraint on its squared amplitude is varied.

  16. Roles of STAT3 in Protein Secretion Pathways during the Acute-Phase Response

    PubMed Central

    Ahyi, Ayele-Nati N.; Quinton, Lee J.; Jones, Matthew R.; Ferrari, Joseph D.; Pepper-Cunningham, Zachary A.; Mella, Juan R.; Remick, Daniel G.

    2013-01-01

    The acute-phase response is characteristic of perhaps all infections, including bacterial pneumonia. In conjunction with the acute-phase response, additional biological pathways are induced in the liver and are dependent on the transcription factors STAT3 and NF-κB, but these responses are poorly understood. Here, we demonstrate that pneumococcal pneumonia and other severe infections increase expression of multiple components of the cellular secretory machinery in the mouse liver, including the endoplasmic reticulum (ER) translocon complex, which mediates protein translation into the ER, and the coat protein complexes (COPI and COPII), which mediate vesicular transport of proteins to and from the ER. Hepatocyte-specific mutation of STAT3 prevented the induction of these secretory pathways during pneumonia, with similar results observed following pharmacological activation of ER stress by using tunicamycin. These findings implicate STAT3 in the unfolded protein response and suggest that STAT3-dependent optimization of secretion may apply broadly. Pneumonia also stimulated the binding of phosphorylated STAT3 to promoter regions of secretion-related genes in the liver, supporting a direct role for STAT3 in their transcription. Altogether, these results identify a novel function of STAT3 during the acute-phase response, namely, the induction of secretory machinery in hepatocytes. This may facilitate the processing and delivery of newly synthesized loads of acute-phase proteins, enhancing innate immunity and preventing liver injury during infection. PMID:23460517

  17. Hemocyte differentiation mediates the mosquito late-phase immune response against Plasmodium in Anopheles gambiae

    PubMed Central

    Smith, Ryan C.; Barillas-Mury, Carolina; Jacobs-Lorena, Marcelo

    2015-01-01

    Plasmodium parasites must complete development in the mosquito vector for transmission to occur. The mosquito innate immune response is remarkably efficient in limiting parasite numbers. Previous work has identified a LPS-induced TNFα transcription factor (LITAF)-like transcription factor, LITAF-like 3 (LL3), which significantly influences parasite numbers. Here, we demonstrate that LL3 does not influence invasion of the mosquito midgut epithelium or ookinete-to-oocyst differentiation but mediates a late-phase immune response that decreases oocyst survival. LL3 expression in the midgut and hemocytes is activated by ookinete midgut invasion and is independent of the mosquito microbiota, suggesting that LL3 may be a component of a wound-healing response. LL3 silencing abrogates the ability of mosquito hemocytes to differentiate and respond to parasite infection, implicating hemocytes as critical modulators of the late-phase immune response. PMID:26080400

  18. Hemocyte differentiation mediates the mosquito late-phase immune response against Plasmodium in Anopheles gambiae.

    PubMed

    Smith, Ryan C; Barillas-Mury, Carolina; Jacobs-Lorena, Marcelo

    2015-06-30

    Plasmodium parasites must complete development in the mosquito vector for transmission to occur. The mosquito innate immune response is remarkably efficient in limiting parasite numbers. Previous work has identified a LPS-induced TNFα transcription factor (LITAF)-like transcription factor, LITAF-like 3 (LL3), which significantly influences parasite numbers. Here, we demonstrate that LL3 does not influence invasion of the mosquito midgut epithelium or ookinete-to-oocyst differentiation but mediates a late-phase immune response that decreases oocyst survival. LL3 expression in the midgut and hemocytes is activated by ookinete midgut invasion and is independent of the mosquito microbiota, suggesting that LL3 may be a component of a wound-healing response. LL3 silencing abrogates the ability of mosquito hemocytes to differentiate and respond to parasite infection, implicating hemocytes as critical modulators of the late-phase immune response. PMID:26080400

  19. Responses of macaque ganglion cells to the relative phase of heterochromatically modulated lights.

    PubMed Central

    Smith, V C; Lee, B B; Pokorny, J; Martin, P R; Valberg, A

    1992-01-01

    1. We measured the response of macaque ganglion cells to sinusoidally modulated red and green lights as the relative phase, theta, of the lights was varied. 2. At low frequencies, red-green ganglion cells of the parvocellular (PC-) pathway with opponent inputs from middle-wavelength sensitive (M-) and long-wavelength sensitive (L-) cones were minimally sensitive to luminance modulation (theta = 0 deg) and maximally sensitive to chromatic modulation (theta = 180 deg). With increasing frequency, the phase, theta, of minimal amplitude gradually changed, in opposite directions for cells with M- and L-cone centres. 3. At high frequencies (at and above 20 Hz), phasic cells of the magnocellular (MC-) pathway were maximally responsive when theta approximately 0 deg and minimally responsive when theta approximately 180 deg, as expected from an achromatic mechanism. At lower frequencies, the phase of minimal response shifted, for both on- and off-centre cells, to values of theta intermediate between 0 and 180 deg. This phase asymmetry was absent if the centre alone was stimulated with a small field. 4. For PC-pathway cells, it was possible to provide an account of response phase as a function of theta, using a model involving three parameters; phases of the L- and M-cone mechanisms and a L/M cone weighting term. For red-green cells, the phase parameters were monotonically related to temporal frequency and revealed a centre-surround phase difference. The phase difference was linear with a slope of 1-3 deg Hz-1. If this represents a latency difference, it would be 3-8 ms. Otherwise, temporal properties of the M- and L-cones appeared similar if not identical. By addition of a scaling term, the model could be extended to give an adequate account of the amplitude of responses. 5. We were able to activate selectively the surrounds of cells with short-wavelength (S-) cone input to their centres, and so were able to assess L/M cone weighting to the surround. M- and L-cone inputs

  20. Intrinsically Disordered Energy Landscapes

    NASA Astrophysics Data System (ADS)

    Chebaro, Yassmine; Ballard, Andrew J.; Chakraborty, Debayan; Wales, David J.

    2015-05-01

    Analysis of an intrinsically disordered protein (IDP) reveals an underlying multifunnel structure for the energy landscape. We suggest that such ‘intrinsically disordered’ landscapes, with a number of very different competing low-energy structures, are likely to characterise IDPs, and provide a useful way to address their properties. In particular, IDPs are present in many cellular protein interaction networks, and several questions arise regarding how they bind to partners. Are conformations resembling the bound structure selected for binding, or does further folding occur on binding the partner in a induced-fit fashion? We focus on the p53 upregulated modulator of apoptosis (PUMA) protein, which adopts an -helical conformation when bound to its partner, and is involved in the activation of apoptosis. Recent experimental evidence shows that folding is not necessary for binding, and supports an induced-fit mechanism. Using a variety of computational approaches we deduce the molecular mechanism behind the instability of the PUMA peptide as a helix in isolation. We find significant barriers between partially folded states and the helix. Our results show that the favoured conformations are molten-globule like, stabilised by charged and hydrophobic contacts, with structures resembling the bound state relatively unpopulated in equilibrium.

  1. Intrinsically Disordered Energy Landscapes

    PubMed Central

    Chebaro, Yassmine; Ballard, Andrew J.; Chakraborty, Debayan; Wales, David J.

    2015-01-01

    Analysis of an intrinsically disordered protein (IDP) reveals an underlying multifunnel structure for the energy landscape. We suggest that such ‘intrinsically disordered’ landscapes, with a number of very different competing low-energy structures, are likely to characterise IDPs, and provide a useful way to address their properties. In particular, IDPs are present in many cellular protein interaction networks, and several questions arise regarding how they bind to partners. Are conformations resembling the bound structure selected for binding, or does further folding occur on binding the partner in a induced-fit fashion? We focus on the p53 upregulated modulator of apoptosis (PUMA) protein, which adopts an -helical conformation when bound to its partner, and is involved in the activation of apoptosis. Recent experimental evidence shows that folding is not necessary for binding, and supports an induced-fit mechanism. Using a variety of computational approaches we deduce the molecular mechanism behind the instability of the PUMA peptide as a helix in isolation. We find significant barriers between partially folded states and the helix. Our results show that the favoured conformations are molten-globule like, stabilised by charged and hydrophobic contacts, with structures resembling the bound state relatively unpopulated in equilibrium. PMID:25999294

  2. Intrinsically disordered energy landscapes.

    PubMed

    Chebaro, Yassmine; Ballard, Andrew J; Chakraborty, Debayan; Wales, David J

    2015-01-01

    Analysis of an intrinsically disordered protein (IDP) reveals an underlying multifunnel structure for the energy landscape. We suggest that such 'intrinsically disordered' landscapes, with a number of very different competing low-energy structures, are likely to characterise IDPs, and provide a useful way to address their properties. In particular, IDPs are present in many cellular protein interaction networks, and several questions arise regarding how they bind to partners. Are conformations resembling the bound structure selected for binding, or does further folding occur on binding the partner in a induced-fit fashion? We focus on the p53 upregulated modulator of apoptosis (PUMA) protein, which adopts an α-helical conformation when bound to its partner, and is involved in the activation of apoptosis. Recent experimental evidence shows that folding is not necessary for binding, and supports an induced-fit mechanism. Using a variety of computational approaches we deduce the molecular mechanism behind the instability of the PUMA peptide as a helix in isolation. We find significant barriers between partially folded states and the helix. Our results show that the favoured conformations are molten-globule like, stabilised by charged and hydrophobic contacts, with structures resembling the bound state relatively unpopulated in equilibrium. PMID:25999294

  3. Predicting intrinsic brain activity.

    PubMed

    Craddock, R Cameron; Milham, Michael P; LaConte, Stephen M

    2013-11-15

    Multivariate supervised learning methods exhibit a remarkable ability to decode externally driven sensory, behavioral, and cognitive states from functional neuroimaging data. Although they are typically applied to task-based analyses, supervised learning methods are equally applicable to intrinsic effective and functional connectivity analyses. The obtained models of connectivity incorporate the multivariate interactions between all brain regions simultaneously, which will result in a more accurate representation of the connectome than the ones available with standard bivariate methods. Additionally the models can be applied to decode or predict the time series of intrinsic brain activity of a region from an independent dataset. The obtained prediction accuracy provides a measure of the integration between a brain region and other regions in its network, as well as a method for evaluating acquisition and preprocessing pipelines for resting state fMRI data. This article describes a method for learning multivariate models of connectivity. The method is applied in the non-parametric prediction accuracy, influence, and reproducibility-resampling (NPAIRS) framework, to study the regional variation of prediction accuracy and reproducibility (Strother et al., 2002). The resulting spatial distribution of these metrics is consistent with the functional hierarchy proposed by Mesulam (1998). Additionally we illustrate the utility of the multivariate regression connectivity modeling method for optimizing experimental parameters and assessing the quality of functional neuroimaging data. PMID:23707580

  4. Elastin-like Polypeptides as Models of Intrinsically Disordered Proteins

    PubMed Central

    Roberts, Stefan; Dzuricky, Michael; Chilkoti, Ashutosh

    2015-01-01

    Elastin-like polypeptides (ELPs) are a class of stimuli-responsive biopolymers inspired by the intrinsically disordered domains of tropoelastin that are composed of repeats of the VPGXG pentapeptide motif, where X is a “guest residue”. They undergo a reversible, thermally triggered lower critical solution temperature (LCST) phase transition, which has been utilized for a variety of applications including protein purification, affinity capture, immunoassays, and drug delivery. ELPs have been extensively studied as protein polymers and as biomaterials, but their relationship to other disordered proteins has heretofore not been established. The biophysical properties of ELPs that lend them their unique material behavior are similar to the properties of many intrinsically disordered proteins (IDP). Their low sequence complexity, phase behavior, and elastic properties make them an interesting “minimal” artificial IDP, and the study of ELPs can hence provide insights into the behavior of other more complex IDPs. Motivated by this emerging realization of the similarities between ELPs and IDPs, this review discusses the biophysical properties of ELPs, their biomedical utility, and their relationship to other disordered polypeptide sequences. PMID:26325592

  5. Effect of phase shifts in pressure-flow relationship on response to inspiratory resistance.

    PubMed

    Younes, M; Sanii, R

    1989-08-01

    Inspiratory prolongation is an integral component of the response to added inspiratory resistance. To ascertain whether this response depends on the relation between inspiratory flow (V) and the pressure perturbation, we compared the responses when this relationship was made progressively less distinct by creating phase shifts between V and the resulting negative mouth pressure (Pm). This was done with an apparatus that altered Pm in proportion to V (J. Appl. Physiol. 62:2491-2499, 1987). V was passed through low-pass electronic filters of different frequency responses before serving as the command signal to the apparatus. In six normal subjects the average neural inspiratory duration (TI) response (delta TI) was sharply (P less than 0.01) reduced (0.32 +/- 0.07 to 0.12 +/- 0.07 s) when the filter's frequency response decreased from 7.5 to 3.0 Hz. The TI response was essentially flat between tube resistance (i.e., no lag, delta TI = 0.36 +/- 0.11 s) and the 7.5-Hz filter, and there was no further change in TI response with filters having a frequency response less than 3.0 Hz, with all TI responses in this range being not significant. Subjects could not consciously perceive a difference between various filter settings. We conclude that the TI response is critically influenced by the phase of the negative pressure wave relative to TI. Furthermore the TI responses are not deliberate, although consciousness is required for their elicitation. PMID:2676945

  6. Optically addressed and submillisecond response phase only liquid crystal spatial light modulator

    NASA Astrophysics Data System (ADS)

    Zhao, Xiangjie; Duan, Jiazhu; Zhang, Dayong; Luo, Yongquan

    2014-10-01

    Liquid crystal based phase only spatial light modulator has attracted many research interests since last decades because of its superior advantage. Until now the liquid crystal spatial light modulator has been applied in many fields, but the response speed of nematic LC limited its further application. In this paper, an optically addressed phase only LC spatial light modulator was proposed based on polymer network liquid crystal. Morphology effect on the light scattering of PNLC was studied, which was mainly consisted of fiber and fiber bundles. The morphology nearly determined the light scattering and electro-optical property. Due to the high threshold voltage, to address the PNLC phase modulator was also concerned. Optical addressing method was proposed, in which BSO crystal was selected to replace one of the glass substrate. The response speed of PNLC was so fast that the reorientation of liquid crystal director will follow the change of effective voltage applied on LC layer, which was related with the voltage signal and especially with electron transport of photo-induced carriers due to diffusion and drift. The on state dynamic response of phase change was investigated. Based on this device, beam steering was also achieved by loading 488nm laser strip on the optical addressed phase only spatial light modulator.

  7. Investigating the Temporal Patterns within and between Intrinsic Connectivity Networks under Eyes-Open and Eyes-Closed Resting States: A Dynamical Functional Connectivity Study Based on Phase Synchronization

    PubMed Central

    Wang, Xun-Heng; Li, Lihua; Xu, Tao; Ding, Zhongxiang

    2015-01-01

    The brain active patterns were organized differently under resting states of eyes open (EO) and eyes closed (EC). The altered voxel-wise and regional-wise resting state active patterns under EO/EC were found by static analysis. More importantly, dynamical spontaneous functional connectivity has been observed in the resting brain. To the best of our knowledge, the dynamical mechanisms of intrinsic connectivity networks (ICNs) under EO/EC remain largely unexplored. The goals of this paper were twofold: 1) investigating the dynamical intra-ICN and inter-ICN temporal patterns during resting state; 2) analyzing the altered dynamical temporal patterns of ICNs under EO/EC. To this end, a cohort of healthy subjects with scan conditions of EO/EC were recruited from 1000 Functional Connectomes Project. Through Hilbert transform, time-varying phase synchronization (PS) was applied to evaluate the inter-ICN synchrony. Meanwhile, time-varying amplitude was analyzed as dynamical intra-ICN temporal patterns. The results found six micro-states of inter-ICN synchrony. The medial visual network (MVN) showed decreased intra-ICN amplitude during EC relative to EO. The sensory-motor network (SMN) and auditory network (AN) exhibited enhanced intra-ICN amplitude during EC relative to EO. Altered inter-ICN PS was found between certain ICNs. Particularly, the SMN and AN exhibited enhanced PS to other ICNs during EC relative to EO. In addition, the intra-ICN amplitude might influence the inter-ICN synchrony. Moreover, default mode network (DMN) might play an important role in information processing during EO/EC. Together, the dynamical temporal patterns within and between ICNs were altered during different scan conditions of EO/EC. Overall, the dynamical intra-ICN and inter-ICN temporal patterns could benefit resting state fMRI-related research, and could be potential biomarkers for human functional connectome. PMID:26469182

  8. 40 CFR 35.6570 - Use of the same engineer during subsequent phases of response.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... it selected the engineer and the code of conduct requirements described in 40 CFR 31.36(b)(3). (ii... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Use of the same engineer during... Agreement § 35.6570 Use of the same engineer during subsequent phases of response. (a) If the public...

  9. Modulation of the acute phase response in feedlot steers supplemented with Saccharomyces cerevisiae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was designed to determine the effect of supplementing feedlot steers with Saccharomyces cerevisiae CNCM I-1079 (SC) on the acute phase response to a lipopolysaccharide (LPS) challenge. Steers (n = 18; 266 ± 4 kilograms body weight) were separated into three treatment groups (n = 6/treatm...

  10. Altered postnatal acute phase response in heifers exposed to lipopolysachcharide in utero

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to determine the effect of prenatal lipopolysaccharide (LPS) exposure on the postnatal acute phase response (APR) to LPS challenge in heifer calves. Pregnant crossbred cows (n=50) were separated into prenatal stress (PNS; n=25; administered 0.1 microgram per kilogram...

  11. Profile of the bovine acute-phase response following an intravenous bolus-dose lipopolysaccharide challenge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Two experiments were conducted to further define the acute-phase response to a lipopolysaccharide (LPS) challenge in beef steers. In Exp. 1, 9 crossbred beef steers (449 ± 12 kg BW) were used in a completely random design to determine the effects of 0.5, 1.0, or 2.0 micrograms of LPS/kilogram of bod...

  12. Phase Response Synchronization in Neuronal Population with Time-Varying Coupling Strength

    PubMed Central

    Jiao, Xianfa; Zhao, Wanyu; Cao, Jinde

    2015-01-01

    We present the dynamic model of global coupled neuronal population subject to external stimulus by the use of phase sensitivity function. We investigate the effect of time-varying coupling strength on the synchronized phase response of neural population subjected to external harmonic stimulus. For a time-periodic coupling strength, we found that the stimulus with increasing intensity or frequency can reinforce the phase response synchronization in neuronal population of the weakly coupled neural oscillators, and the neuronal population with stronger coupling strength has good adaptability to stimulus. When we consider the dynamics of coupling strength, we found that a strong stimulus can quickly cause the synchronization in the neuronal population, the degree of synchronization grows with the increasing stimulus intensity, and the period of synchronized oscillation induced by external stimulation is related to stimulus frequency. PMID:26640514

  13. Electromagnetic response of time-reversal breaking metallic phases in two dimensions

    NASA Astrophysics Data System (ADS)

    Chua, Victor; Assawasunthonnet, Wathid; Fradkin, Eduardo

    The electromagnetic response of models of nematic non Fermi-liquids previously proposed in Ref. are re-examined using conventional many-body methods. Nematic phases of this model are described by two 2-component real vectors which express the isotropy breaking nematicity in two Fermi-surfaces. Of interest is the time-reversal symmetry breaking nematic phase with a non-vanishing unquantized spontaneous anomalous Hall effect at zero external magnetic fields, and has a geometrical description as a Berry phase. We compare and contrast our results with conventional response calculations with those predicted with the higher-dimensional bosonization method. Finally we present preliminary results on an RG analysis of this system. This work was supported by the Gordon and Betty Moore Foundation.

  14. Phase and period responses of the jerboa Jaculus orientalis to short light pulses.

    PubMed

    El Moussaouiti, Rachid; Bouhaddou, Nezha; Sabbar, Mariam; Cooper, Howard M; Lakhdar-Ghazal, Nouria

    2010-08-01

    The phase and period responses to short light pulses were studied in the jerboa, a seasonal, hibernating, nocturnal rodent from the Atlas region in Morocco. The jerboa, which is a saltatory species, showed precise activity onsets and offsets under a light-dark (LD) cycle using infrared captors to record locomotor activity. When released into constant darkness (DD), the majority of animals showed a circadian period (tau) < 24 h (mean tau = 23.89 +/- 0.13 h) and a lengthening of the activity span, alpha. Animals were subsequently exposed to up to eight 15-min light pulses, each separated by at least 2 wks, for up to 160 days in DD. During this span, most individuals maintained robust circadian rhythmicity, with clearly defined activity onsets and offsets, similar levels of total activity, duration of alpha, and percent activity occurring during the subjective night. The phase response curve (PRC) is typical of other nocturnal rodents, with light eliciting delays during late subjective day and early subjective night (CT8-CT19) and advances during late subjective night to early subjective day (CT19-CT2). A dead zone, when light had no effect on phase, is observed during mid-subjective day (CT3-CT8). A few individuals showed large (> 9 h) Type 0 phase resetting near the singularity region (CT19) that resulted in a complete phase reversal, but otherwise displayed normal phase-shifting responses at other CT times. The tau response curve showed a decrease in period from early to late subjective night with increases at other times, but these changes were small (maximum < 9 min) and highly variable. There was a distinct tendency for animals that had an initial short tau in DD to conserve a short tau during the series of light pulses and, inversely, for animals with long tau to conserve a long tau. This suggests possible constraints on the plasticity of variation of tau in relation to the endogenous period of the animal. PMID:20795880

  15. EGR Control for Emisson Reduction Using Fast Response Sensors - Phase 1A

    SciTech Connect

    Gravel, Roland; Conley, Jason; Kittelson, David

    2008-09-30

    The overall objective of this project was to develop exhaust gas recirculation (EGR) control strategies using fast-response Particulate Matter (PM) sensors and NOx sensors to improve the quality of particulate and gaseous emissions from diesel engines. This project initially comprised three phases: (1) Phase IA - sensor requirements to meet PM sensor specifications, NOx sensor assessment, and initial model development for EGR control; (2) Phase IB - continue development on PM and NOx sensors, integrate the sensor signals into the control simulations, and finalize model development for control strategies; and (3) Phase II - validation testing of the control strategies. Only Phase 1A was funded by DOE and executed by Honeywell. The major objectives of Phase 1A of the project included: (1) Sensor validation and operation of fast-response PM and NOx sensors; (2) Control system modeling of low-pressure EGR controls, development of control strategies, and initial evaluation of these models and strategies for EGR control in diesel engines; (3) Sensor testing to understand applicability of fast-response PM sensors in determining loading rates of the particle trap; and (4) Model validation and sensor testing under steady-state and transient operational conditions of actual engines. In particular, specific objectives included demonstration of: (1) A PM sensor response time constant (T10 - T90) of better than 100 milliseconds (msec); (2) The ability to detect PM at concentrations from 0.2 to 2 Bosch smoke number (BSN) or equivalent; (3) PM sensor accuracy to within 20% BSN over the entire range of operation; and (4) PM sensor repeatability to within 10% over the PM entire sensor range equivalent to a BSN of 0.2 to 2.

  16. Using Geo-Data Corporately on the Response Phase of Emergency Management

    NASA Astrophysics Data System (ADS)

    Demir Ozbek, E.; Ates, S.; Aydinoglu, A. C.

    2015-08-01

    Response phase of emergency management is the most complex phase in the entire cycle because it requires cooperation between various actors relating to emergency sectors. A variety of geo-data is needed at the emergency response such as; existing data provided by different institutions and dynamic data collected by different sectors at the time of the disaster. Disaster event is managed according to elaborately defined activity-actor-task-geodata cycle. In this concept, every activity of emergency response is determined with Standard Operation Procedure that enables users to understand their tasks and required data in any activity. In this study, a general conceptual approach for disaster and emergency management system is developed based on the regulations to serve applications in Istanbul Governorship Provincial Disaster and Emergency Directorate. The approach is implemented to industrial facility explosion example. In preparation phase, optimum ambulance locations are determined according to general response time of the ambulance to all injury cases in addition to areas that have industrial fire risk. Management of the industrial fire case is organized according to defined actors, activities, and working cycle that describe required geo-data. A response scenario was prepared and performed for an industrial facility explosion event to exercise effective working cycle of actors. This scenario provides using geo-data corporately between different actors while required data for each task is defined to manage the industrial facility explosion event. Following developing web technologies, this scenario based approach can be effective to use geo-data on the web corporately.

  17. Intrinsic evolutions of dielectric function and electronic transition in tungsten doping Ge{sub 2}Sb{sub 2}Te{sub 5} phase change films discovered by ellipsometry at elevated temperatures

    SciTech Connect

    Guo, S.; Ding, X. J.; Zhang, J. Z.; Hu, Z. G. Chu, J. H.; Ji, X. L.; Wu, L. C.; Song, Z. T.

    2015-02-02

    Tungsten (W) doping effects on Ge{sub 2}Sb{sub 2}Te{sub 5} (GSTW) phase change films with different concentrations (3.2, 7.1, and 10.8%) have been investigated by variable-temperature spectroscopic ellipsometry. The dielectric functions from 210 K to 660 K have been evaluated with the aid of Tauc-Lorentz and Drude dispersion models. The analysis of Tauc gap energy (E{sub g}) and partial spectral weight integral reveal the correlation between optical properties and local structural change. The order degree increment and chemical bond change from covalent to resonant should be responsible for band gap narrowing and electronic transition enhancement during the phase change process. It is found that the elevated crystalline temperature for GSTW can be related to improved disorder degree. Furthermore, the shrinkage of E{sub g} for GSTW should be attributed to the enhanced metallicity compared with undoped GST.

  18. Magneto-optical response in the arbitrary-Chern number topological phase on square lattice

    NASA Astrophysics Data System (ADS)

    Wang, Yi-Xiang

    2016-07-01

    In this work, we investigate the magneto-optical response in the arbitrary-Chern number topological phase. Based on the Dirac theory, we derive the analytic expressions for the magneto-optical response. More importantly, we construct the model on the possible square lattice and make the numerical calculations with the exact diagonalization method. We find the analytical and numerical results are in good agreement with each other. For the optical absorption spectrum, the low-energy absorptive peaks and the corresponding hopping processes are distinct in different Chern number phases, heavily depending on the filling factor of the system. While for the optical Hall conductivities, the physical mechanisms are revealed for the dichroism of the absorption peaks in response to the right- and left-circularly polarized light. We discuss the feasibility of these results in experiment.

  19. Intrinsic Feature Motion Tracking

    Energy Science and Technology Software Center (ESTSC)

    2013-03-19

    Subject motion during 3D medical scanning can cause blurring and artifacts in the 3D images resulting in either rescans or poor diagnosis. Anesthesia or physical restraints may be used to eliminate motion but are undesirable and can affect results. This software measures the six degree of freedom 3D motion of the subject during the scan under a rigidity assumption using only the intrinsic features present on the subject area being monitored. This movement over timemore » can then be used to correct the scan data removing the blur and artifacts. The software acquires images from external cameras or images stored on disk for processing. The images are from two or three calibrated cameras in a stereo arrangement. Algorithms extract and track the features over time and calculate position and orientation changes relative to an initial position. Output is the 3D position and orientation change measured at each image.« less

  20. Intrinsic anion oxidation potentials.

    PubMed

    Johansson, Patrik

    2006-11-01

    Anions of lithium battery salts have been investigated by electronic structure calculations with the objective to find a computational measure to correlate with the observed (in)stability of nonaqueous lithium battery electrolytes vs oxidation often encountered in practice. Accurate prediction of intrinsic anion oxidation potentials is here made possible by computing the vertical free energy difference between anion and neutral radical (Delta Gv) and further strengthened by an empirical correction using only the anion volume as a parameter. The 6-311+G(2df,p) basis set, the VSXC functional, and the C-PCM SCRF algorithm were used. The Delta Gv calculations can be performed using any standard computational chemistry software. PMID:17078600

  1. Intrinsic Feature Motion Tracking

    SciTech Connect

    Goddard, Jr., James S.

    2013-03-19

    Subject motion during 3D medical scanning can cause blurring and artifacts in the 3D images resulting in either rescans or poor diagnosis. Anesthesia or physical restraints may be used to eliminate motion but are undesirable and can affect results. This software measures the six degree of freedom 3D motion of the subject during the scan under a rigidity assumption using only the intrinsic features present on the subject area being monitored. This movement over time can then be used to correct the scan data removing the blur and artifacts. The software acquires images from external cameras or images stored on disk for processing. The images are from two or three calibrated cameras in a stereo arrangement. Algorithms extract and track the features over time and calculate position and orientation changes relative to an initial position. Output is the 3D position and orientation change measured at each image.

  2. Intrinsically variable stars

    NASA Technical Reports Server (NTRS)

    Bohm-Vitense, Erika; Querci, Monique

    1987-01-01

    The characteristics of intrinsically variable stars are examined, reviewing the results of observations obtained with the IUE satellite since its launch in 1978. Selected data on both medium-spectral-class pulsating stars (Delta Cep stars, W Vir stars, and related groups) and late-type variables (M, S, and C giants and supergiants) are presented in spectra, graphs, and tables and described in detail. Topics addressed include the calibration of the the period-luminosity relation, Cepheid distance determination, checking stellar evolution theory by the giant companions of Cepheids, Cepheid masses, the importance of the hydrogen convection zone in Cepheids, temperature and abundance estimates for Population II pulsating stars, mass loss in Population II Cepheids, SWP and LWP images of cold giants and supergiants, temporal variations in the UV lines of cold stars, C-rich cold stars, and cold stars with highly ionized emission lines.

  3. A three pulse phase response curve to three milligrams of melatonin in humans

    PubMed Central

    Burgess, Helen J; Revell, Victoria L; Eastman, Charmane I

    2008-01-01

    Exogenous melatonin is increasingly used for its phase shifting and soporific effects. We generated a three pulse phase response curve (PRC) to exogenous melatonin (3 mg) by administering it to free-running subjects. Young healthy subjects (n = 27) participated in two 5 day laboratory sessions, each preceded by at least a week of habitual, but fixed sleep. Each 5 day laboratory session started and ended with a phase assessment to measure the circadian rhythm of endogenous melatonin in dim light using 30 min saliva samples. In between were three days in an ultradian dim light (< 150 lux)–dark cycle (LD 2.5 : 1.5) during which each subject took one pill per day at the same clock time (3 mg melatonin or placebo, double blind, counterbalanced). Each individual's phase shift to exogenous melatonin was corrected by subtracting their phase shift to placebo (a free-run). The resulting PRC has a phase advance portion peaking about 5 h before the dim light melatonin onset, in the afternoon. The phase delay portion peaks about 11 h after the dim light melatonin onset, shortly after the usual time of morning awakening. A dead zone of minimal phase shifts occurred around the first half of habitual sleep. The fitted maximum advance and delay shifts were 1.8 h and 1.3 h, respectively. This new PRC will aid in determining the optimal time to administer exogenous melatonin to achieve desired phase shifts and demonstrates that using exogenous melatonin as a sleep aid at night has minimal phase shifting effects. PMID:18006583

  4. Dynamics of cellular immune responses in the acute phase of dengue virus infection.

    PubMed

    Yoshida, Tomoyuki; Omatsu, Tsutomu; Saito, Akatsuki; Katakai, Yuko; Iwasaki, Yuki; Kurosawa, Terue; Hamano, Masataka; Higashino, Atsunori; Nakamura, Shinichiro; Takasaki, Tomohiko; Yasutomi, Yasuhiro; Kurane, Ichiro; Akari, Hirofumi

    2013-06-01

    In this study, we examined the dynamics of cellular immune responses in the acute phase of dengue virus (DENV) infection in a marmoset model. Here, we found that DENV infection in marmosets greatly induced responses of CD4/CD8 central memory T and NKT cells. Interestingly, the strength of the immune response was greater in animals infected with a dengue fever strain than in those infected with a dengue hemorrhagic fever strain of DENV. In contrast, when animals were re-challenged with the same DENV strain used for primary infection, the neutralizing antibody induced appeared to play a critical role in sterilizing inhibition against viral replication, resulting in strong but delayed responses of CD4/CD8 central memory T and NKT cells. The results in this study may help to better understand the dynamics of cellular and humoral immune responses in the control of DENV infection. PMID:23381396

  5. Phase-field simulation of domain structures and magnetostrictive response in Tb1-xDyxFe2 alloys near morphotropic phase boundary

    NASA Astrophysics Data System (ADS)

    Hu, Cheng-Chao; Yang, Tian-Nan; Huang, Hou-Bing; Hu, Jia-Mian; Wang, Jian-Jun; Shi, Yang-Guang; Shi, Da-Ning; Chen, Long-Qing

    2016-04-01

    Phase-field method micromagnetic microelastic modeling is employed to simulate the thermal domain stability and enhanced magnetostrictive responses around the ferromagnetic morphotropic phase boundary (MPB) in giant magnetostrictive Tb1-xDyxFe2 ( x ≈0.27 ) single crystal. The simulation shows that the rhombohedral and tetragonal phases coexist in equilibrium in the vicinity of MPB region due to the balance of weak magnetocrystalline anisotropy and strong exchange, magnetostatic and ferroelastic interaction. Enhanced magnetostrictive response is found in the vicinity of MPB, which could be attributed to the low-energy rotating pathways of local magnetization vectors in the phase coexisting region.

  6. Liver genomic responses to ciguatoxin: evidence for activation of phase I and phase II detoxification pathways following an acute hypothermic response in mice.

    PubMed

    Morey, Jeanine S; Ryan, James C; Bottein Dechraoui, Marie-Yasmine; Rezvani, Amir H; Levin, Edward D; Gordon, Christopher J; Ramsdell, John S; Van Dolah, Frances M

    2008-06-01

    Ciguatoxins (CTX) are polyether neurotoxins that target voltage-gated sodium channels and are responsible for ciguatera, the most common fish-borne food poisoning in humans. This study characterizes the global transcriptional response of mouse liver to a symptomatic dose (0.26 ng/g) of the highly potent Pacific ciguatoxin-1 (P-CTX-1). At 1 h post-exposure 2.4% of features on a 44K whole genome array were differentially expressed (p < or = 0.0001), increasing to 5.2% at 4 h and decreasing to 1.4% by 24 h post-CTX exposure. Data were filtered (/fold change/ > or = 1.5 and p < or = 0.0001 in at least one time point) and a trend set of 1550 genes were used for further analysis. Early gene expression was likely influenced prominently by an acute 4 degrees C decline in core body temperature by 1 h, which resolved by 8 h following exposure. An initial downregulation of 32 different solute carriers, many involved in sodium transport, was observed. Differential gene expression in pathways involving eicosanoid biosynthesis and cholesterol homeostasis was also noted. Cytochrome P450s (Cyps) were of particular interest due to their role in xenobiotic metabolism. Twenty-seven genes, mostly members of Cyp2 and Cyp4 families, showed significant changes in expression. Many Cyps underwent an initial downregulation at 1 h but were quickly and strongly upregulated at 4 and 24 h post-exposure. In addition to Cyps, increases in several glutathione S-transferases were observed, an indication that both phase I and phase II metabolic reactions are involved in the hepatic response to CTX in mice. PMID:18353800

  7. Visual stimuli recruit intrinsically generated cortical ensembles

    PubMed Central

    Miller, Jae-eun Kang; Ayzenshtat, Inbal; Carrillo-Reid, Luis; Yuste, Rafael

    2014-01-01

    The cortical microcircuit is built with recurrent excitatory connections, and it has long been suggested that the purpose of this design is to enable intrinsically driven reverberating activity. To understand the dynamics of neocortical intrinsic activity better, we performed two-photon calcium imaging of populations of neurons from the primary visual cortex of awake mice during visual stimulation and spontaneous activity. In both conditions, cortical activity is dominated by coactive groups of neurons, forming ensembles whose activation cannot be explained by the independent firing properties of their contributing neurons, considered in isolation. Moreover, individual neurons flexibly join multiple ensembles, vastly expanding the encoding potential of the circuit. Intriguingly, the same coactive ensembles can repeat spontaneously and in response to visual stimuli, indicating that stimulus-evoked responses arise from activating these intrinsic building blocks. Although the spatial properties of stimulus-driven and spontaneous ensembles are similar, spontaneous ensembles are active at random intervals, whereas visually evoked ensembles are time-locked to stimuli. We conclude that neuronal ensembles, built by the coactivation of flexible groups of neurons, are emergent functional units of cortical activity and propose that visual stimuli recruit intrinsically generated ensembles to represent visual attributes. PMID:25201983

  8. Functional and metabolic properties of alveolar macrophages in response to the gas phase of tobacco smoke.

    PubMed Central

    Drath, D B; Shorey, J M; Huber, G L

    1981-01-01

    The effect of whole tobacco smoke and the gas phase of tobacco smoke on the metabolism and phagocytic ability of alveolar macrophages was monitored over a 30-day exposure period. It was demonstrated that both the gas phase and whole tobacco smoke induced a weight loss in exposed rats. Alveolar macrophage oxygen consumption was markedly increased by both exposure regimens. Superoxide generation was not affected by whole tobacco smoke exposure but was increased in response to the filtered gas phase. Hexose monophosphate shunt activity was not altered by either treatment. When metabolic alterations were seen in response to the separate exposures, they were seen only after a phagocytic challenge to the macrophage and not when the cell was unchallenged. Neither whole tobacco smoke nor the gas phase had any significant effect on the ability of alveolar macrophages to phagocytize a viable challenge of Staphylococcus aureus. Our results suggest that many of the metabolic and functional effects of tobacco smoke on alveolar macrophages can be attributed to the gas-phase component of whole tobacco smoke. PMID:6271676

  9. Functional and metabolic properties of alveolar macrophages in response to the gas phase of tobacco smoke.

    PubMed

    Drath, D B; Shorey, J M; Huber, G L

    1981-10-01

    The effect of whole tobacco smoke and the gas phase of tobacco smoke on the metabolism and phagocytic ability of alveolar macrophages was monitored over a 30-day exposure period. It was demonstrated that both the gas phase and whole tobacco smoke induced a weight loss in exposed rats. Alveolar macrophage oxygen consumption was markedly increased by both exposure regimens. Superoxide generation was not affected by whole tobacco smoke exposure but was increased in response to the filtered gas phase. Hexose monophosphate shunt activity was not altered by either treatment. When metabolic alterations were seen in response to the separate exposures, they were seen only after a phagocytic challenge to the macrophage and not when the cell was unchallenged. Neither whole tobacco smoke nor the gas phase had any significant effect on the ability of alveolar macrophages to phagocytize a viable challenge of Staphylococcus aureus. Our results suggest that many of the metabolic and functional effects of tobacco smoke on alveolar macrophages can be attributed to the gas-phase component of whole tobacco smoke. PMID:6271676

  10. Frequency and phase synchronization in neuromagnetic cortical responses to flickering-color stimuli

    NASA Astrophysics Data System (ADS)

    Timashev, S. F.; Polyakov, Yu. S.; Yulmetyev, R. M.; Demin, S. A.; Panischev, O. Yu.; Shimojo, S.; Bhattacharya, J.

    2010-03-01

    In our earlier study dealing with the analysis of neuromagnetic responses (magnetoencephalograms—MEG) to flickering-color stimuli for a group of control human subjects (9 volunteers) and a patient with photosensitive epilepsy (a 12-year old girl), it was shown that Flicker-Noise Spectroscopy (FNS) was able to identify specific differences in the responses of each organism. The high specificity of individual MEG responses manifested itself in the values of FNS parameters for both chaotic and resonant components of the original signal. The present study applies the FNS cross-correlation function to the analysis of correlations between the MEG responses simultaneously measured at spatially separated points of the human cortex processing the red-blue flickering color stimulus. It is shown that the cross-correlations for control (healthy) subjects are characterized by frequency and phase synchronization at different points of the cortex, with the dynamics of neuromagnetic responses being determined by the low-frequency processes that correspond to normal physiological rhythms. But for the patient, the frequency and phase synchronization breaks down, which is associated with the suppression of cortical regulatory functions when the flickering-color stimulus is applied, and higher frequencies start playing the dominating role. This suggests that the disruption of correlations in the MEG responses is the indicator of pathological changes leading to photosensitive epilepsy, which can be used for developing a method of diagnosing the disease based on the analysis with the FNS cross-correlation function.

  11. Cell-intrinsic role for IFN-α–STAT1 signals in regulating murine Peyer patch plasmacytoid dendritic cells and conditioning an inflammatory response

    PubMed Central

    Li, Haiyan S.; Gelbard, Alexander; Martinez, Gustavo J.; Esashi, Eiji; Zhang, Huiyuan; Nguyen-Jackson, Hoainam; Liu, Yong-Jun; Overwijk, Willem W.

    2011-01-01

    Plasmacytoid dendritic cells (pDCs) reside in bone marrrow and lymphoid organs in homeostatic conditions and typically secrete abundant quantities of type I interferons (IFNs) on Toll-like receptor triggering. Recently, a pDC population was identified within Peyer patches (PPs) of the gut that is distinguished by its lack of IFN production; however, the relationship of PP pDCs to pDCs in other organs has been unclear. We report that PP pDCs are derived from common DC progenitors and accumulate in response to Fms-like tyrosine kinase 3 ligand, yet appear divergent in transcription factor profile and surface marker phenotype, including reduced E2-2 and CCR9 expression. Type I IFN signaling via STAT1 has a cell-autonomous role in accrual of PP pDCs in vivo. Moreover, IFN-α enhances pDC generation from DC progenitors by a STAT1-dependent mechanism. pDCs that have been developed in the presence of IFN-α resemble PP pDCs, produce inflammatory cytokines, stimulate Th17 cell generation, and fail to secrete IFN-α on Toll-like receptor engagement. These results indicate that IFN-α influences the development and function of pDCs by inducing emergence of an inflammatory (Th17-inducing) antigen-presenting subset, and simultaneously regulating accumulation of pDCs in the intestinal microenvironment. PMID:21828128

  12. Lytic Gene Expression Is Frequent in HSV-1 Latent Infection and Correlates with the Engagement of a Cell-Intrinsic Transcriptional Response

    PubMed Central

    Ma, Joel Z.; Russell, Tiffany A.; Spelman, Tim

    2014-01-01

    Herpes simplex viruses (HSV) are significant human pathogens that provide one of the best-described examples of viral latency and reactivation. HSV latency occurs in sensory neurons, being characterized by the absence of virus replication and only fragmentary evidence of protein production. In mouse models, HSV latency is especially stable but the detection of some lytic gene transcription and the ongoing presence of activated immune cells in latent ganglia have been used to suggest that this state is not entirely quiescent. Alternatively, these findings can be interpreted as signs of a low, but constant level of abortive reactivation punctuating otherwise silent latency. Using single cell analysis of transcription in mouse dorsal root ganglia, we reveal that HSV-1 latency is highly dynamic in the majority of neurons. Specifically, transcription from areas of the HSV genome associated with at least one viral lytic gene occurs in nearly two thirds of latently-infected neurons and more than half of these have RNA from more than one lytic gene locus. Further, bioinformatics analyses of host transcription showed that progressive appearance of these lytic transcripts correlated with alterations in expression of cellular genes. These data show for the first time that transcription consistent with lytic gene expression is a frequent event, taking place in the majority of HSV latently-infected neurons. Furthermore, this transcription is of biological significance in that it influences host gene expression. We suggest that the maintenance of HSV latency involves an active host response to frequent viral activity. PMID:25058429

  13. Intelligent Viscoelastic Polyurethane Intrinsic Nanocomposites

    NASA Astrophysics Data System (ADS)

    Bilal Khan, M.

    2010-04-01

    Polyurethanes are multiphase systems comprising intrinsically variant nanodomains. The material properties can be tailored by adjusting the relative proportions and organizing the structure of the hard and soft segments akin to the spring-dashpot system in an automobile. This article describes how an intelligent polyurethane (PU) system is created to offer smart response to mechanical and vibration stimuli. In this work, unidirectional, dynamic mechanical thermal analysis (DMTA), acoustic, and impact testing results are qualified with the unique viscoelastic character that determines the rate-temperature response of the nanocomposite. Attenuated total reflection- infrared spectroscopy (ATR-IR) and DMTA offer a logical explanation of the observed viscoelastic behavior in terms of the nanodomains. Enhanced nanophase segregation between the polymer building blocks (hard and soft segments) is the primary mechanism that leads to a higher loss tangent peak in DMTA at a lower glass transition temperature ( T g ) for greater energy dissipation in the polymer matrix. Acoustic and impact attenuation are correlated with the mechanical modulus and loss tangent of the polymer. Finally, autodyne simulation reveals the unique shock absorbent behavior of the material layer when retrofitted to concrete structure. Typically, shock overpressure spikes of the order of 9.97 × 104 MPa experienced by the unprotected surface are entirely evened out at a lower overpressure threshold.

  14. Optical information authentication using compressed double-random-phase-encoded images and quick-response codes.

    PubMed

    Wang, Xiaogang; Chen, Wen; Chen, Xudong

    2015-03-01

    In this paper, we develop a new optical information authentication system based on compressed double-random-phase-encoded images and quick-response (QR) codes, where the parameters of optical lightwave are used as keys for optical decryption and the QR code is a key for verification. An input image attached with QR code is first optically encoded in a simplified double random phase encoding (DRPE) scheme without using interferometric setup. From the single encoded intensity pattern recorded by a CCD camera, a compressed double-random-phase-encoded image, i.e., the sparse phase distribution used for optical decryption, is generated by using an iterative phase retrieval technique with QR code. We compare this technique to the other two methods proposed in literature, i.e., Fresnel domain information authentication based on the classical DRPE with holographic technique and information authentication based on DRPE and phase retrieval algorithm. Simulation results show that QR codes are effective on improving the security and data sparsity of optical information encryption and authentication system. PMID:25836845

  15. Phase-Locked Responses to Speech in Human Auditory Cortex are Enhanced During Comprehension

    PubMed Central

    Peelle, Jonathan E.; Gross, Joachim; Davis, Matthew H.

    2013-01-01

    A growing body of evidence shows that ongoing oscillations in auditory cortex modulate their phase to match the rhythm of temporally regular acoustic stimuli, increasing sensitivity to relevant environmental cues and improving detection accuracy. In the current study, we test the hypothesis that nonsensory information provided by linguistic content enhances phase-locked responses to intelligible speech in the human brain. Sixteen adults listened to meaningful sentences while we recorded neural activity using magnetoencephalography. Stimuli were processed using a noise-vocoding technique to vary intelligibility while keeping the temporal acoustic envelope consistent. We show that the acoustic envelopes of sentences contain most power between 4 and 7 Hz and that it is in this frequency band that phase locking between neural activity and envelopes is strongest. Bilateral oscillatory neural activity phase-locked to unintelligible speech, but this cerebro-acoustic phase locking was enhanced when speech was intelligible. This enhanced phase locking was left lateralized and localized to left temporal cortex. Together, our results demonstrate that entrainment to connected speech does not only depend on acoustic characteristics, but is also affected by listeners’ ability to extract linguistic information. This suggests a biological framework for speech comprehension in which acoustic and linguistic cues reciprocally aid in stimulus prediction. PMID:22610394

  16. Antioxidants attenuate multiple phases of formalin-induced nociceptive response in mice.

    PubMed

    Hacimuftuoglu, A; Handy, C R; Goettl, V M; Lin, C G; Dane, S; Stephens, R L

    2006-10-16

    An emerging theme in the study of the pathophysiology of chronic and persistent pain is the role of pro-oxidant substances. Reactive oxygen species (ROS) have been implicated in contributing to and/or maintaining conditions of chronic pain. Recent pre-clinical reports suggest that antioxidants are effective analgesics in neuropathic and inflammatory pain models. The present study extends this work by examining the effect of three antioxidants on tissue injury-induced nociception. C57BL6 mice (20-25 g) were pretreated with either phenyl-N-tert-butylnitrone (PBN; 50 mg/kg, i.p.), 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxy (TEMPOL; 200 or 50 mg/kg, i.p.), N-acetyl-L-cysteine (NAC; 200 or 100mg/kg, i.p.), or vehicle (0.5 ml/100 g), 5 min before intraplantar formalin (10%, 20 microl) injection. Nociceptive responding, indicated by licking or biting the affected hindlimb, was quantified for 30 min after formalin injection. Each drug was effective in attenuating two or more phases (acute, quiescent, and tonic) of the formalin response. To assess putative site of action, intrathecal TEMPOL (380 nmol/5 microl, i.t.) was given 5 min before intraplantar formalin. Intrathecal TEMPOL produced a 83% reduction in nociceptive responding in the tonic phase, but no significant attenuation of the acute phase response. To confirm that the antioxidant property of intrathecal TEMPOL was responsible for its analgesic effect on the formalin-induced pain response, intrathecal TEMPOL was coadministered with the free radical donor tert-butylhydroperoxide (tert-BuOOH). Tert-BuOOH coadminstration reversed the TEMPOL-induced analgesia in the tonic intraplantar formalin response reduction. The data suggest that pro-oxidant species may be important mediators of tissue injury-induced algesia in rodents, and that a spinal site of action is implicated in the tonic response. PMID:16919817

  17. Ultrafast, high resolution, phase contrast imaging of impact response with synchrotron radiation

    SciTech Connect

    Jensen, B. J.; Luo, S. N.; Hooks, D. E.; Ramos, K. J.; Yeager, J. D.; Kwiatkowski, K.; Shimada, T.; Dattelbaum, D. M.; Fezzaa, K.

    2012-03-15

    Understanding the dynamic response of materials at extreme conditions requires diagnostics that can provide real-time, in situ, spatially resolved measurements on the nanosecond timescale. The development of methods such as phase contrast imaging (PCI) typically used at synchrotron sources offer unique opportunities to examine dynamic material response. In this work, we report ultrafast, high-resolution, dynamic PCI measurements of shock compressed materials with 3 {mu}m spatial resolution using a single 60 ps synchrotron X-ray bunch. These results firmly establish the use of PCI to examine dynamic phenomena at ns to {mu}s timescales.

  18. Self-consistent continuum random-phase approximation calculations of {sup 4}He electromagnetic responses

    SciTech Connect

    De Donno, V.; Co', G.; Anguiano, M.; Lallena, A. M.

    2011-09-15

    We study the electromagnetic responses of {sup 4}He within the framework of the self-consistent continuum random-phase approximation theory. In this approach, the ground-state properties are described by a Hartree-Fock calculation. The single-particle basis constructed in this manner is used in the calculations of the continuum responses of the system. Finite-range interactions are considered in the calculations. We compare our results with photon-absorption cross sections and electron-scattering quasielastic data. From this comparison, and also from the comparison with the results of microscopic calculations, we deduce that our approach describes well the continuum excitation.

  19. Simulated response of top-hat electrostatic analysers - importance of phase-space resolution

    NASA Astrophysics Data System (ADS)

    De Marco, Rossana; Bruno, Roberto; D'Amicis, Raffaella; Federica Marcucci, Maria; Servidio, Sergio; Valentini, Francesco

    2016-04-01

    We use a numerical code able to reproduce the angular/energy response of a typical electrostatic analyzer of top-hat type starting from velocity distribution functions (VDFs) generated by numerical imulations.The simulations are based on the Hybrid Vlasov-Maxwell (HVM) numerical algorithm which integrates the Vlasov equation for the ion distribution function in multi-dimensional geometry in phase space, while the electrons are treated as a fluid. Virtual satellites launched through the simulation box measure the particle VDFs. Such VDFs are interpolated into a spacecraft reference frame and moved from the simulation Cartesian grid to energy-angular coordinates to mimic the response of a real electrostatic sensor in the solar wind and in the magnetosheath for different conditions. We discuss the results of this study with respect to the importance of phase-space resolution for a space plasma experiment meant to investigate kinetic plasma regime.

  20. Toward phase 4 trials in heart failure: A social and corporate responsibility of the medical profession.

    PubMed

    Iyngkaran, Pupalan; Beneby, Glen S

    2015-12-26

    Congestive heart failure (CHF) is a chronic condition, requiring polypharmacy, allied health supports and regular monitoring. All these factors are needed to ensure compliance and to deliver the positive outcomes demonstrated from randomized controlled trials. Unfortunately many centers around the world are unable to match trial level support. The outcomes for many communities are thus unclear. Research design factors in post-marketing surveillance to address this issue. Phase 4 studies is the name given to trials designed to obtain such community level data and thus address issues of external validity. CHF phase 4 studies are relatively underutilized. We feel the onus for this research lies with the health profession. In this commentary we provide arguments as to why phase 4 studies should be viewed as a social and corporate responsibility of health professional that care for clients with CHF. PMID:26713277

  1. Toward phase 4 trials in heart failure: A social and corporate responsibility of the medical profession

    PubMed Central

    Iyngkaran, Pupalan; Beneby, Glen S

    2015-01-01

    Congestive heart failure (CHF) is a chronic condition, requiring polypharmacy, allied health supports and regular monitoring. All these factors are needed to ensure compliance and to deliver the positive outcomes demonstrated from randomized controlled trials. Unfortunately many centers around the world are unable to match trial level support. The outcomes for many communities are thus unclear. Research design factors in post-marketing surveillance to address this issue. Phase 4 studies is the name given to trials designed to obtain such community level data and thus address issues of external validity. CHF phase 4 studies are relatively underutilized. We feel the onus for this research lies with the health profession. In this commentary we provide arguments as to why phase 4 studies should be viewed as a social and corporate responsibility of health professional that care for clients with CHF. PMID:26713277

  2. Melatonin shifts human circadian rhythms according to a phase-response curve.

    PubMed

    Lewy, A J; Ahmed, S; Jackson, J M; Sack, R L

    1992-10-01

    A physiological dose of orally administered melatonin shifts circadian rhythms in humans according to a phase-response curve (PRC) that is nearly opposite in phase with the PRCs for light exposure: melatonin delays circadian rhythms when administered in the morning and advances them when administered in the afternoon or early evening. The human melatonin PRC provides critical information for using melatonin to treat circadian phase sleep and mood disorders, as well as maladaptation to shift work and transmeridional air travel. The human melatonin PRC also provides the strongest evidence to date for a function of endogenous melatonin and its suppression by light in augmenting entrainment of circadian rhythms by the light-dark cycle. PMID:1394610

  3. Sex differences in acute hormonal and subjective response to naltrexone: the impact of menstrual cycle phase

    PubMed Central

    Roche, Daniel J.O.; King, Andrea C.

    2015-01-01

    Women often exhibit larger hormonal and subjective responses to opioid receptor antagonists than men, but the biological mechanisms mediating this effect remain unclear. Among women, fluctuations in estradiol (E2) and progesterone (P4) across the menstrual cycle (MC) affect the endogenous opioid system. Therefore, the goal of the current study was to compare acute naltrexone response between women in the early follicular phase of the MC (low E2 and P4), women in the luteal phase of the MC (high E2 and P4), and men. Seventy healthy controls (n = 46 women) participated in two morning sessions in which they received 50 mg naltrexone or placebo in a randomized, counterbalanced order. Women were randomized to complete both sessions in either the early follicular (n = 23) or luteal phase of the MC. Serum cortisol, prolactin, and luteinizing hormone (LH), salivary cortisol, and subjective response were assessed upon arrival to the laboratory and at regular intervals after pill administration. In luteal and early follicular women but not men, naltrexone (vs. placebo) increased serum cortisol and prolactin levels from baseline; however, the naltrexone-induced increases in these hormones were significantly greater in luteal women than early follicular women. Additionally, only luteal women demonstrated an increase from baseline in salivary cortisol levels and the severity of adverse drug effects in response to naltrexone. In sum, the results indicate that luteal phase women are more sensitive to acute hormonal and subjective effects of naltrexone than early follicular women and men. These findings may have important implications for the use of naltrexone in women. PMID:25459893

  4. Sex differences in acute hormonal and subjective response to naltrexone: The impact of menstrual cycle phase.

    PubMed

    Roche, Daniel J O; King, Andrea C

    2015-02-01

    Women often exhibit larger hormonal and subjective responses to opioid receptor antagonists than men, but the biological mechanisms mediating this effect remain unclear. Among women, fluctuations in estradiol (E2) and progesterone (P4) across the menstrual cycle (MC) affect the endogenous opioid system. Therefore, the goal of the current study was to compare acute naltrexone response between women in the early follicular phase of the MC (low E2 and P4), women in the luteal phase of the MC (high E2 and P4), and men. Seventy healthy controls (n=46 women) participated in two morning sessions in which they received 50mg naltrexone or placebo in a randomized, counterbalanced order. Women were randomized to complete both sessions in either the early follicular (n=23) or luteal phase of the MC. Serum cortisol, salivary cortisol, prolactin, luteinizing hormone (LH), and subjective response were assessed upon arrival to the laboratory and at regular intervals after pill administration. In luteal and early follicular women but not men, naltrexone (vs. placebo) increased serum cortisol and prolactin levels from baseline; however, the naltrexone-induced increases in these hormones were significantly greater in luteal women than early follicular women. Additionally, only luteal women demonstrated an increase from baseline in salivary cortisol levels and the severity of adverse drug effects in response to naltrexone. In sum, the results indicate that luteal phase women are more sensitive to acute hormonal and subjective effects of naltrexone than early follicular women and men. These findings may have important implications for the use of naltrexone in women. PMID:25459893

  5. Modeling the viscoplastic micromechanical response of two-phase materials using fast Fourier transforms

    SciTech Connect

    Lebensohn, Ricardo A; Lee, Sukbin; Rollett, Anthony D

    2009-01-01

    A viscoplastic approach using the Fast Fourier Transform (FFT) method for obtaining local mechanical response is utilized to study microstructure-property relationships in composite materials. Specifically, three-dimensional, two-phase digital materials containing isotropically coarsened particles surrounded by a matrix phase, generated through a Kinetic Monte Carlo Potts model for Ostwald ripening, are used as instantiations in order to calculate the stress and strain rate fields under uniaxial tension. The effects of the morphology of the matrix phase, the volume fraction and the contiguity of particles, and the polycrystallinity of matrix phase, on the stress and strain rate fields under uniaxial tension are examined. It is found that the first moments of the stress and strain rate fields have a different dependence on the particle volume fraction and the particle contiguity from their second moments. The average stresses and average strain rates of both phases and of the overall composite have rather simple relationships with the particle volume fraction whereas their standard deviations vary strongly, especially when the particle volume fraction is high, and the contiguity of particles has a noticeable effect on the mechanical response. It is also found that the shape of stress distribution in the BCC hard particle phase evolves as the volume fraction of particles in the composite varies, such that it agrees with the stress field in the BCC polycrystal as the volume of particles approaches unity. Finally, it is observed that the stress and strain rate fields in the microstructures with a polycrystalline matrix are less sensitive to changes in volume fraction and contiguity of particles.

  6. Hydration-responsive folding and unfolding in graphene oxide liquid crystal phases.

    PubMed

    Guo, Fei; Kim, Franklin; Han, Tae Hee; Shenoy, Vivek B; Huang, Jiaxing; Hurt, Robert H

    2011-10-25

    Graphene oxide is promising as a plate-like giant molecular building block for the assembly of new carbon materials. Its water dispersibility, liquid crystallinity, and ease of reduction offer advantages over other carbon precursors if its fundamental assembly rules can be identified. This article shows that graphene oxide sheets of known lateral dimension form nematic liquid crystal phases with transition points in agreement with the Onsager hard-plate theory. The liquid crystal phases can be systematically ordered into defined supramolecular patterns using surface anchoring, complex fluid flow, and microconfinement. Graphene oxide is seen to exhibit homeotropic surface anchoring at interfaces driven by excluded volume entropy and by adsorption enthalpy associated with its partially hydrophobic basal planes. Surprisingly, some of the surface-ordered graphene oxide phases dry into graphene oxide solids that undergo a dramatic anisotropic swelling upon rehydration to recover their initial size and shape. This behavior is shown to be a unique hydration-responsive folding and unfolding transition. During drying, surface tension forces acting parallel to the layer planes cause a buckling instability that stores elastic energy in accordion-folded structures in the dry solid. Subsequent water infiltration reduces interlayer frictional forces and triggers release of the stored elastic energy in the form of dramatic unidirectional expansion. We explain the folding/unfolding phenomena by quantitative nanomechanics and introduce the potential of liquid crystal-derived graphene oxide phases as new stimuli-response materials. PMID:21877716

  7. Hydration-Responsive Folding and Unfolding in Graphene Oxide Liquid Crystal Phases

    PubMed Central

    Guo, Fei; Kim, Franklin; Han, Tae Hee; Shenoy, Vivek B.; Huang, Jiaxing; Hurt, Robert H.

    2011-01-01

    Graphene oxide is promising as a plate-like giant molecular building block for the assembly of new carbon materials. Its water dispersibility, liquid crystallinity, and ease of reduction offer advantages over other carbon precursors if its fundamental assembly rules can be identified. This article shows that graphene oxide sheets of known lateral dimension form nematic liquid crystal phases with transition points in agreement with the Onsager hard-plate theory. The liquid crystal phases can be systematic ordered into defined supramolecular patterns using surface anchoring, complex fluid flow, and micro-confinement. Graphene oxide is seen to exhibit homeotropic surface anchoring at interfaces driven by excluded volume entropy and by adsorption enthalpy associated with its partially hydrophobic basal planes. Surprisingly, some of the surface-ordered graphene oxide phases dry into graphene oxide solids that undergo a dramatic anisotropic swelling upon rehydration to recover their initial size and shape. This behavior is shown to be a unique hydration-responsive folding and unfolding transition. During drying, surface tension forces acting parallel to the layer planes cause a buckling instability that stores elastic energy in accordion-folded structures in the dry solid. Subsequent water infiltration reduces interlayer frictional forces and triggers release of the stored elastic energy in the form of dramatic unidirectional expansion. We explain the folding/unfolding phenomena by quantitative nanomechanics, and introduce the potential of liquid crystal-derived graphene oxide phases as new stimuli-response materials. PMID:21877716

  8. Early responses of human cancer cells upon photodynamic treatment monitored by laser phase microscopy

    NASA Astrophysics Data System (ADS)

    Roelofs, Theo A.; Graschew, Georgi; Perevedentseva, Elena V.; Rakowsky, Stefan; Dressler, Cathrin; Beuthan, Juergen; Schlag, Peter M.

    2001-04-01

    Photodynamic treatment of cancer cells is known to eventually cause cell death in most cases. The precise pathways and the time course seem to vary among different cell types and modes of photodynamic treatment. In this contribution, the focus was put on the responses of human colon carcinoma cells HCT-116 within the first 15 minutes after laser irradiation in the presence of Photofrin« II (PII). To monitor the cell response in this early time period laser phase microscopic imaging was used, a method sensitive to changes in overall cell shape and intracellular structures, mediated by changes in the local refractive index. Laser irradiation of cells loaded with PII induced a significant reduction of the phase shifts, which probably reflects the induced damage to the different cellular membrane structures. The data suggest that even within the first 30 s after the onset of laser illumination, a significant reduction of the phase shifts can be detected. These results underline that laser phase microscopy is a suitable diagnostic tool for cellular research, also in the early time domain.

  9. Visualizing phase transition behavior of dilute stimuli responsive polymer solutions via Mueller matrix polarimetry.

    PubMed

    Narayanan, Amal; Chandel, Shubham; Ghosh, Nirmalya; De, Priyadarsi

    2015-09-15

    Probing volume phase transition behavior of superdiluted polymer solutions both micro- and macroscopically still persists as an outstanding challenge. In this regard, we have explored 4 × 4 spectral Mueller matrix measurement and its inverse analysis for excavating the microarchitectural facts about stimuli responsiveness of "smart" polymers. Phase separation behavior of thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) and pH responsive poly(N,N-(dimethylamino)ethyl methacrylate) (PDMAEMA) and their copolymers were analyzed in terms of Mueller matrix derived polarization parameters, namely, depolarization (Δ), diattenuation (d), and linear retardance (δ). The Δ, d, and δ parameters provided useful information on both macro- and microstructural alterations during the phase separation. Additionally, the two step action ((i) breakage of polymer-water hydrogen bonding and (ii) polymer-polymer aggregation) at the molecular microenvironment during the cloud point generation was successfully probed via these parameters. It is demonstrated that, in comparison to the present techniques available for assessing the hydrophobic-hydrophilic switch over of simple stimuli-responsive polymers, Mueller matrix polarimetry offers an important advantage requiring a few hundred times dilute polymer solution (0.01 mg/mL, 1.1-1.4 μM) at a low-volume format. PMID:26287499

  10. Phase Response Design of Recursive All-Pass Digital Filters Using a Modified PSO Algorithm

    PubMed Central

    Chang, Wei-Der

    2015-01-01

    This paper develops a new design scheme for the phase response of an all-pass recursive digital filter. A variant of particle swarm optimization (PSO) algorithm will be utilized for solving this kind of filter design problem. It is here called the modified PSO (MPSO) algorithm in which another adjusting factor is more introduced in the velocity updating formula of the algorithm in order to improve the searching ability. In the proposed method, all of the designed filter coefficients are firstly collected to be a parameter vector and this vector is regarded as a particle of the algorithm. The MPSO with a modified velocity formula will force all particles into moving toward the optimal or near optimal solution by minimizing some defined objective function of the optimization problem. To show the effectiveness of the proposed method, two different kinds of linear phase response design examples are illustrated and the general PSO algorithm is compared as well. The obtained results show that the MPSO is superior to the general PSO for the phase response design of digital recursive all-pass filter. PMID:26366168

  11. Comparative Transcriptomics Indicates a Role for SHORT VEGETATIVE PHASE (SVP) Genes in Mimulus guttatus Vernalization Response

    PubMed Central

    Preston, Jill C.; Zhong, Jinshun; McKeown, Meghan; den Bakker, Meghan; Friedman, Jannice

    2016-01-01

    The timing of reproduction in response to variable environmental conditions is critical to plant fitness, and is a major driver of taxon differentiation. In the yellow monkey flower, Mimulus guttatus, geographically distinct North American populations vary in their photoperiod and chilling (vernalization) requirements for flowering, suggesting strong local adaptation to their surroundings. Previous analyses revealed quantitative trait loci (QTL) underlying short-day mediated vernalization responsiveness using two annual M. guttatus populations that differed in their vernalization response. To narrow down candidate genes responsible for this variation, and to reveal potential downstream genes, we conducted comparative transcriptomics and quantitative PCR (qPCR) in shoot apices of parental vernalization responsive IM62, and unresponsive LMC24 inbred lines grown under different photoperiods and temperatures. Our study identified several metabolic, hormone signaling, photosynthetic, stress response, and flowering time genes that are differentially expressed between treatments, suggesting a role for their protein products in short-day-mediated vernalization responsiveness. Only a small subset of these genes intersected with candidate genes from the previous QTL study, and, of the main candidates tested with qPCR under nonpermissive conditions, only SHORT VEGETATIVE PHASE (SVP) gene expression met predictions for a population-specific short-day-repressor of flowering that is repressed by cold. PMID:26921300

  12. Comparative Transcriptomics Indicates a Role for SHORT VEGETATIVE PHASE (SVP) Genes in Mimulus guttatus Vernalization Response.

    PubMed

    Preston, Jill C; Zhong, Jinshun; McKeown, Meghan; den Bakker, Meghan; Friedman, Jannice

    2016-01-01

    The timing of reproduction in response to variable environmental conditions is critical to plant fitness, and is a major driver of taxon differentiation. In the yellow monkey flower, Mimulus guttatus, geographically distinct North American populations vary in their photoperiod and chilling (vernalization) requirements for flowering, suggesting strong local adaptation to their surroundings. Previous analyses revealed quantitative trait loci (QTL) underlying short-day mediated vernalization responsiveness using two annual M. guttatus populations that differed in their vernalization response. To narrow down candidate genes responsible for this variation, and to reveal potential downstream genes, we conducted comparative transcriptomics and quantitative PCR (qPCR) in shoot apices of parental vernalization responsive IM62, and unresponsive LMC24 inbred lines grown under different photoperiods and temperatures. Our study identified several metabolic, hormone signaling, photosynthetic, stress response, and flowering time genes that are differentially expressed between treatments, suggesting a role for their protein products in short-day-mediated vernalization responsiveness. Only a small subset of these genes intersected with candidate genes from the previous QTL study, and, of the main candidates tested with qPCR under nonpermissive conditions, only SHORT VEGETATIVE PHASE (SVP) gene expression met predictions for a population-specific short-day-repressor of flowering that is repressed by cold. PMID:26921300

  13. Intrinsic Angular Momentum of Light.

    ERIC Educational Resources Information Center

    Santarelli, Vincent

    1979-01-01

    Derives a familiar torque-angular momentum theorem for the electromagnetic field, and includes the intrinsic torques exerted by the fields on the polarized medium. This inclusion leads to the expressions for the intrinsic angular momentum carried by the radiation traveling through a charge-free medium. (Author/MA)

  14. The Role of Plasma Membrane Intrinsic Protein Aquaporins in Water Transport through Roots: Diurnal and Drought Stress Responses Reveal Different Strategies between Isohydric and Anisohydric Cultivars of Grapevine1[OA

    PubMed Central

    Vandeleur, Rebecca K.; Mayo, Gwenda; Shelden, Megan C.; Gilliham, Matthew; Kaiser, Brent N.; Tyerman, Stephen D.

    2009-01-01

    We report physiological and anatomical characteristics of water transport across roots grown in soil of two cultivars of grapevine (Vitis vinifera) differing in response to water stress (Grenache, isohydric; Chardonnay, anisohydric). Both cultivars have similar root hydraulic conductances (Lo; normalized to root dry weight) that change diurnally. There is a positive correlation between Lo and transpiration. Under water stress, both cultivars have reduced minimum daily Lo (predawn) attributed to the development of apoplastic barriers. Water-stressed and well-watered Chardonnay had the same diurnal change in amplitude of Lo, while water-stressed Grenache showed a reduction in daily amplitude compared with well-watered plants. Hydraulic conductivity of root cortex cells (Lpcell) doubles in Chardonnay but remains unchanged in Grenache. Of the two most highly expressed plasma membrane intrinsic protein (PIP) aquaporins in roots (VvPIP1;1 and VvPIP2;2), only VvPIP2;2 functions as a water channel in Xenopus laevis oocytes. VvPIP1;1 interacts with VvPIP2;2 to induce 3-fold higher water permeability. These two aquaporins are colocated in the root from in situ hybridization and immunolocalization of VvPIP1 and VvPIP2 subfamily members. They occur in root tip, exodermis, root cortex (detected up to 30 mm), and stele. VvPIP2;2 mRNA does not change diurnally or with water stress, in contrast to VvPIP1;1, in which expression reflects the differences in Lo and Lpcell between cultivars in their responses to water stress and rewatering. VvPIP1;1 may regulate water transport across roots such that transpirational demand is matched by root water transport capacity. This occurs on a diurnal basis and in response to water stress that corresponds to the difference in drought tolerance between the cultivars. PMID:18987216

  15. Psychophysiological responses to overloading and tapering phases in elite young soccer players.

    PubMed

    Freitas, Camila G; Aoki, Marcelo S; Franciscon, Clovis A; Arruda, Ademir F S; Carling, Christopher; Moreira, Alexandre

    2014-05-01

    This study investigated the effect of a 2-week overloading training phase followed by a 2-week tapering phase on internal training load (ITL), salivary cortisol, stress tolerance, and upper respiratory tract infections symptoms (URTI) in 11 male young soccer players (16.0 ± 0.5 yrs). Ratings of perceived exertion (session- RPE) were taken after each training session (N = 194) to determine ITL. Saliva sampling was conducted at the end of each week and cortisol concentration assessed by ELISA. DALDA and WURSS-21 questionnaires were administered every week to evaluate stress tolerance and severity of URTI respectively. The number of athletes reporting URTI symptoms was recorded. The overloading phase promoted greater ITL and a higher resting cortisol concentration than the tapering phase (P < .05). While no significant changes in stress tolerance or URTI severity were observed, the number of athletes reporting URTI symptoms was higher during the overloading phase. A significant correlation was observed between symptoms of stress and severity of URTI (rs=-.71; P = .01). The results indicate that an integrated approach using psychological measures (session-RPE and DALDA), self-reports of URTI symptoms, and endocrine responses (cortisol) to training are pertinent for monitoring young soccer players. PMID:24722819

  16. Ceramide mediates the rapid phase of febrile response to IL-1β

    PubMed Central

    Sanchez-Alavez, Manuel; Tabarean, Iustin V.; Behrens, M. Margarita; Bartfai, Tamas

    2006-01-01

    IL-1β was identified after a long search for the endogenous pyrogen. It acts by inducing synthesis of prostaglandin E2, which mediates the late phase of IL-1β-induced fever. Here we show by radiotelemetry that the early phase of the fever response to IL-1β is mediated by ceramide. Hypothalamic application of the cell-penetrating C2-ceramide mimics the rapid phase of the IL-1β-induced fever. Inhibition of ceramide synthesis blocks the rapid phase of fever but does not affect the slower prostaglandin E2-dependent phase, which is blocked by indomethacin or by null mutation of the EP3 prostanoid receptor. Electrophysiological experiments on preoptic area/anterior hypothalamic neurons show that C2-ceramide, but not dihydroceramide, mimics the rapid hyperpolarizing effects of IL-1β on the activity of warm-sensitive hypothalamic neurons. IL-1β-mediated hyperpolarization is blocked by PP2, the selective inhibitor of the protein tyrosine kinase Src, which is known to be activated by ceramide. These in vivo and in vitro data suggest that ceramide fulfills the criteria for an endogenous pyrogen. PMID:16477014

  17. Ceramide mediates the rapid phase of febrile response to IL-1beta.

    PubMed

    Sanchez-Alavez, Manuel; Tabarean, Iustin V; Behrens, M Margarita; Bartfai, Tamas

    2006-02-21

    IL-1beta was identified after a long search for the endogenous pyrogen. It acts by inducing synthesis of prostaglandin E2, which mediates the late phase of IL-1beta-induced fever. Here we show by radiotelemetry that the early phase of the fever response to IL-1beta is mediated by ceramide. Hypothalamic application of the cell-penetrating C2-ceramide mimics the rapid phase of the IL-1beta-induced fever. Inhibition of ceramide synthesis blocks the rapid phase of fever but does not affect the slower prostaglandin E2-dependent phase, which is blocked by indomethacin or by null mutation of the EP3 prostanoid receptor. Electrophysiological experiments on preoptic area/anterior hypothalamic neurons show that C2-ceramide, but not dihydroceramide, mimics the rapid hyperpolarizing effects of IL-1beta on the activity of warm-sensitive hypothalamic neurons. IL-1beta-mediated hyperpolarization is blocked by PP2, the selective inhibitor of the protein tyrosine kinase Src, which is known to be activated by ceramide. These in vivo and in vitro data suggest that ceramide fulfills the criteria for an endogenous pyrogen. PMID:16477014

  18. Extrinsic and intrinsic curvatures in thermodynamic geometry

    NASA Astrophysics Data System (ADS)

    Hosseini Mansoori, Seyed Ali; Mirza, Behrouz; Sharifian, Elham

    2016-08-01

    We investigate the intrinsic and extrinsic curvatures of a certain hypersurface in thermodynamic geometry of a physical system and show that they contain useful thermodynamic information. For an anti-Reissner-Nordström-(A)de Sitter black hole (Phantom), the extrinsic curvature of a constant Q hypersurface has the same sign as the heat capacity around the phase transition points. The intrinsic curvature of the hypersurface can also be divergent at the critical points but has no information about the sign of the heat capacity. Our study explains the consistent relationship holding between the thermodynamic geometry of the KN-AdS black holes and those of the RN (J-zero hypersurface) and Kerr black holes (Q-zero hypersurface) ones [1]. This approach can easily be generalized to an arbitrary thermodynamic system.

  19. Phase-dependent response of the lung to NO sub 2 irritant insult

    SciTech Connect

    Siegel, P.D.; Bozelka, B.E.; Reynolds, C.; George, W.J. )

    1989-07-01

    The biochemical and histopathological response of the lung following acute and repeated (subacute) exposure to nitrogen oxide (NO{sub 2}) was examined. Activities of lactate dehydrogenase, beta-glucuronidase, choline kinase, and protease inhibitor were measured in murine pulmonary tissue immediately and two days following exposure. Nonenzymatic parameters, pulmonary protein content, and wet lung weight were also monitored. Immediately following acute exposure to NO{sub 2}, only the nonenzymatic parameters were elevated. By two days following acute exposure, following subacute exposure; however, the nonenzymatic parameters were attenuated with respect to the enzymatic activities. The lung exhibits a dynamic response following damage by oxidants such as NO{sub 2}. This response is divided into three distinct phases (exudative, proliferative, and tolerant), which can be characterized both biochemically and histopathologically.

  20. Menstrual cycle phase effects free testosterone responses to prolonged aerobic exercise.

    PubMed

    Lane, A R; O'Leary, C B; Hackney, A C

    2015-09-01

    Research has shown that total testosterone (tT) levels in women increase acutely during a prolonged bout of aerobic exercise. Few studies, however, have considered the impact of the menstrual cycle phase on this response or have looked at the biologically active free testosterone (fT) form responses. Therefore, this study examined the fT concentration response independently and as a percentage (fT%) of tT to prolonged aerobic exercise during phases of the menstrual cycle with low estrogen-progesterone (L-EP; i.e., follicular phase) and high estrogen-progesterone (H-EP; i.e., luteal phase). Ten healthy, recreationally trained, eumennorrheic women (X ± SD: age = 20 ± 2 y, mass = 58.7 ± 8.3 kg, body fat = 22.3 ± 4.9 %, VO(2max) = 50.7 ± 9.0 ml/kg/min) participated in a laboratory based study and completed a 60-minute treadmill run during the L-EP and H-EP menstrual phases at ~70% of VO(2max). Blood was drawn prior to (PRE), immediately after (POST) and following 30 minutes of recovery (30POST) with each 60-minute run. During H-EP, there was a significant increase in fT concentrations from PRE to POST (p < 0.01) while in L-EP fT levels were unchanged; which resulted in fT being significantly higher at H-EP POST versus L-EP POST (p < 0.03). Area-under-the-curve (AUC) responses were calculated, for fT the total AUC was greater in H-EP than L-EP (p < 0.04). There was no significant interaction of fT% between phases and exercise sampling time. There was, however, a main effect for exercise where fT% POST was a greater proportion of tT than at PRE (p < 0.01). In summary, hormonal changes associated with the menstrual cycle impact fT response to a prolonged aerobic exercise bout; specifically, there being higher levels under H-EP conditions. This suggests more biologically active T is available during exercise in this phase. This response may be a function of the higher core temperatures found with H-EP causing greater sex hormone binding protein release of T, or could

  1. Phase-locked hippocampal theta-band responses are related to discriminative eyeblink conditioned responding.

    PubMed

    Nokia, Miriam S; Wikgren, Jan

    2013-11-01

    Hippocampal electrophysiological oscillatory activity is undoubtedly related to learning and memory. The relative power of spontaneously occurring hippocampal theta (∼4-8 Hz) oscillations predicts how fast and how well an animal will learn: more theta predicts faster acquisition of the conditioned response in eyeblink conditioning in both rats and rabbits. Here, our aim was to study how hippocampal theta-band responses to conditioned stimuli elicited during very-long delay discrimination eyeblink conditioning relate to the accompanying conditioned behavior. We trained adult male New Zealand White rabbits using 1500-ms auditory stimuli as conditioned stimuli and a 100-ms airpuff as an unconditioned stimulus. The reinforced conditioned stimulus overlapped and co-terminated with the unconditioned stimulus whereas the non-reinforced conditioned stimulus was always presented alone. Consistent with previous results, hippocampal theta-band responses to the conditioned stimuli diminished in amplitude across training. Interestingly, hippocampal theta-band responses were most consistently time-locked when a well-trained animal failed to suppress behavioral learned responses to the non-reinforced conditioned stimulus. We suggest that phase-locking of hippocampal theta-band oscillations in response to external stimuli reflects retrieval of the dominant memory trace (adaptive or not) along with initiating the most prominent action scheme related to that memory trace. PMID:24029698

  2. Cell-mediated response at the muscle phase of Trichinella pseudospiralis and Trichinella spiralis infections.

    PubMed

    Lee, K M; Ko, R C

    2006-06-01

    The cell-mediated response in BALB/c mice infected either by Trichinella pseudospiralis or Trichinella spiralis was compared at days 30-50 post-infection (muscle phase). The former species is non-encapsulated, whereas the latter is encapsulated in host muscles. The pattern of response against the two species was similar. Both species elicited T(H)0 or T(H)1/T(H)2 response, with the last one being dominant. Productions of interferon gamma (IFN-gamma), interleukin (IL)-4 and IL-5 were observed after antigenic restimulation of splenocytes from infected mice. No significant difference was observed between the levels of response to concanavalin A (Con-A) by the splenocytes from both infected and non-infected animals. There was a significant increase in serum IgG(1) and IgG(2a). Flow cytometric analysis revealed a marked proliferative response of splenocytes from infected mice to worm antigens, dominated by B (CD19) lymphoblasts. Only a few helper (CD4+) and cytotoxic (CD8+) T lymphoblasts were present. This was confirmed by an up-regulation of CD69, with a dominant expression on B lymphoblasts. In conclusion, the minimal or lack of intense cellular response against T. pseudospiralis in muscles is likely not due to depression of cell-mediated immunity. PMID:16489472

  3. Cold Responsive Gene Expression Profiling of Sugarcane and Saccharum spontaneum with Functional Analysis of a Cold Inducible Saccharum Homolog of NOD26-Like Intrinsic Protein to Salt and Water Stress

    PubMed Central

    Park, Jong-Won; Benatti, Thiago R.; Marconi, Thiago; Yu, Qingyi; Solis-Gracia, Nora; Mora, Victoria; da Silva, Jorge A.

    2015-01-01

    Transcriptome analysis of sugarcane hybrid CP72-1210 (cold susceptible) and Saccharum spontaneum TUS05-05 (cold tolerant) using Sugarcane Assembled Sequences (SAS) from SUCEST-FUN Database showed that a total of 35,340 and 34,698 SAS genes, respectively, were expressed before and after chilling stress. The analysis revealed that more than 600 genes are differentially expressed in each genotype after chilling stress. Blast2Go annotation revealed that the major difference in gene expression profiles between CP72-1210 and TUS05-05 after chilling stress are present in the genes related to the transmembrane transporter activity. To further investigate the relevance of transmembrane transporter activity against abiotic stress tolerance, a S. spontaneum homolog of a NOD26-like major intrinsic protein gene (SspNIP2) was selected for functional analysis, of which expression was induced after chilling stress in the cold tolerant TUS05-05. Quantitative real-time PCR showed that SspNIP2 expression was increased ~2.5 fold at 30 minutes after cold treatment and stayed induced throughout the 24 hours of cold treatment. The amino acid sequence analysis of the cloned SspNIP2 confirmed the presence of six transmembrane domains and two NPA (Asn-Pro-Ala) motifs, signature features of major intrinsic protein families. Amino acid analysis confirmed that four amino acids, comprising the ar/R (aromatic residue/arginine) region responsible for the substrate specificity among MIPs, are conserved among monocot silicon transporters and SspNIP2. Salinity stress test on SspNIP2 transgenic tobacco plants resulted in more vigorous transgenic lines than the non-transgenic tobacco plants, suggesting some degree of tolerance to salt stress conferred by SspNIP2. SspNIP2-transgenic plants, exposed to 2 weeks of water stress without irrigation, developed various degrees of water stress symptom. The water stress test confirmed that the SspNIP2 transgenic lines had lower evapotranspiration rates than non

  4. Acute Phase Proteins in Response to Dictyocaulus viviparus Infection in Calves

    PubMed Central

    Gånheim, C; Höglund, J; Waller, K Persson

    2004-01-01

    Three experiments were carried out to examine the acute phase response, as measured by the acute phase proteins (APP) haptoglobin, serum amyloid A (SAA) and fibrinogen, in calves infected with lungworm, Dictyocaulus vivparus. In addition, eosinophil counts were analysed. Three different dose models were used in 3 separate experiments: I) 250 D. viviparus infective third stage larvae (L3) once daily for 2 consecutive days, II) 100 D. viviparus L3 once daily for 5 consecutive days, and III) 2000 L3 once. All 3 dose regimes induced elevated levels of haptoglobin, SAA and fibrinogen, although there was considerable variation both between and within experiments. A significant increase was observed in all 3 APP at one or several time points in experiment I and III, whereas in experiment II, the only significant elevation was observed for fibrinogen at one occasion. The eosinophil numbers were significantly elevated in all 3 experiments. The results show that lungworm infection can induce an acute phase response, which can be monitored by the selected APP. Elevated APP levels in combination with high numbers of eosinophils in an animal with respiratory disease may be used as an indicator of lung worm infection, and help the clinician to decide on treatment. However, high numbers of eosinophils and low levels of APP do not exclude a diagnosis of lungworm. Thus, lungworm infection may not be detected if measurements of APP are used to assess calf health in herds or individual animals. PMID:15535088

  5. SnTe field effect transistors and the anomalous electrical response of structural phase transition

    SciTech Connect

    Li, Haitao Zhu, Hao; Yuan, Hui; Li, Qiliang; You, Lin; Kopanski, Joseph J.; Richter, Curt A.; Zhao, Erhai

    2014-07-07

    SnTe is a conventional thermoelectric material and has been newly found to be a topological crystalline insulator. In this work, back-gate SnTe field-effect transistors have been fabricated and fully characterized. The devices exhibit n-type transistor behaviors with excellent current-voltage characteristics and large on/off ratio (>10{sup 6}). The device threshold voltage, conductance, mobility, and subthreshold swing have been studied and compared at different temperatures. It is found that the subthreshold swings as a function of temperature have an apparent response to the SnTe phase transition between cubic and rhombohedral structures at 110 K. The abnormal and rapid increase in subthreshold swing around the phase transition temperature may be due to the soft phonon/structure change which causes the large increase in SnTe dielectric constant. Such an interesting and remarkable electrical response to phase transition at different temperatures makes the small SnTe transistor attractive for various electronic devices.

  6. Intrinsic Negative Mass from Nonlinearity

    NASA Astrophysics Data System (ADS)

    Di Mei, F.; Caramazza, P.; Pierangeli, D.; Di Domenico, G.; Ilan, H.; Agranat, A. J.; Di Porto, P.; DelRe, E.

    2016-04-01

    We propose and provide experimental evidence of a mechanism able to support negative intrinsic effective mass. The idea is to use a shape-sensitive nonlinearity to change the sign of the mass in the leading linear propagation equation. Intrinsic negative-mass dynamics is reported for light beams in a ferroelectric crystal substrate, where the diffusive photorefractive nonlinearity leads to a negative-mass Schrödinger equation. The signature of inverted dynamics is the observation of beams repelled from strongly guiding integrated waveguides irrespective of wavelength and intensity and suggests shape-sensitive nonlinearity as a basic mechanism leading to intrinsic negative mass.

  7. Particle-induced pulmonary acute phase response may be the causal link between particle inhalation and cardiovascular disease

    PubMed Central

    Saber, Anne T; Jacobsen, Nicklas R; Jackson, Petra; Poulsen, Sarah Søs; Kyjovska, Zdenka O; Halappanavar, Sabina; Yauk, Carole L; Wallin, Håkan; Vogel, Ulla

    2014-01-01

    Inhalation of ambient and workplace particulate air pollution is associated with increased risk of cardiovascular disease. One proposed mechanism for this association is that pulmonary inflammation induces a hepatic acute phase response, which increases risk of cardiovascular disease. Induction of the acute phase response is intimately linked to risk of cardiovascular disease as shown in both epidemiological and animal studies. Indeed, blood levels of acute phase proteins, such as C-reactive protein and serum amyloid A, are independent predictors of risk of cardiovascular disease in prospective epidemiological studies. In this review, we present and review emerging evidence that inhalation of particles (e.g., air diesel exhaust particles and nanoparticles) induces a pulmonary acute phase response, and propose that this induction constitutes the causal link between particle inhalation and risk of cardiovascular disease. Increased levels of acute phase mRNA and proteins in lung tissues, bronchoalveolar lavage fluid and plasma clearly indicate pulmonary acute phase response following pulmonary deposition of different kinds of particles including diesel exhaust particles, nanoparticles, and carbon nanotubes. The pulmonary acute phase response is dose-dependent and long lasting. Conversely, the hepatic acute phase response is reduced relative to lung or entirely absent. We also provide evidence that pulmonary inflammation, as measured by neutrophil influx, is a predictor of the acute phase response and that the total surface area of deposited particles correlates with the pulmonary acute phase response. We discuss the implications of these findings in relation to occupational exposure to nanoparticles. How to cite this article: WIREs Nanomed Nanobiotechnol 2014, 6:517–531. doi: 10.1002/wnan.1279 PMID:24920450

  8. Intrinsic Radiosensitivity and Cellular Characterization of 27 Canine Cancer Cell Lines

    PubMed Central

    Maeda, Junko; Froning, Coral E.; Brents, Colleen A.; Rose, Barbara J.; Thamm, Douglas H.; Kato, Takamitsu A.

    2016-01-01

    Canine cancer cell lines have progressively been developed, but are still underused resources for radiation biology research. Measurement of the cellular intrinsic radiosensitivity is important because understanding the difference may provide a framework for further elucidating profiles for prediction of radiation therapy response. Our studies have focused on characterizing diverse canine cancer cell lines in vitro and understanding parameters that might contribute to intrinsic radiosensitivity. First, intrinsic radiosensitivity of 27 canine cancer cell lines derived from ten tumor types was determined using a clonogenic assay. The 27 cell lines had varying radiosensitivities regardless tumor type (survival fraction at 2 Gy, SF2 = 0.19–0.93). In order to understand parameters that might contribute to intrinsic radiosensitivity, we evaluated the relationships of cellular radiosensitivity with basic cellular characteristics of the cell lines. There was no significant correlation of SF2 with S-phase fraction, doubling time, chromosome number, ploidy, or number of metacentric chromosomes, while there was a statistically significant correlation between SF2 and plating efficiency. Next, we selected the five most radiosensitive cell lines as the radiosensitive group and the five most radioresistant cell lines as the radioresistant group. Then, we evaluated known parameters for cell killing by ionizing radiation, including radiation-induced DNA double strand break (DSB) repair and apoptosis, in the radiosensitive group as compared to the radioresistant group. High levels of residual γ-H2AX foci at the sites of DSBs were present in the four out of the five radiosensitive canine cancer cell lines. Our studies suggested that substantial differences in intrinsic radiosensitivity exist in canine cancer cell lines, and radiation-induced DSB repair was related to radiosensitivity, which is consistent with previous human studies. These data may assist further investigations

  9. Intrinsic Radiosensitivity and Cellular Characterization of 27 Canine Cancer Cell Lines.

    PubMed

    Maeda, Junko; Froning, Coral E; Brents, Colleen A; Rose, Barbara J; Thamm, Douglas H; Kato, Takamitsu A

    2016-01-01

    Canine cancer cell lines have progressively been developed, but are still underused resources for radiation biology research. Measurement of the cellular intrinsic radiosensitivity is important because understanding the difference may provide a framework for further elucidating profiles for prediction of radiation therapy response. Our studies have focused on characterizing diverse canine cancer cell lines in vitro and understanding parameters that might contribute to intrinsic radiosensitivity. First, intrinsic radiosensitivity of 27 canine cancer cell lines derived from ten tumor types was determined using a clonogenic assay. The 27 cell lines had varying radiosensitivities regardless tumor type (survival fraction at 2 Gy, SF2 = 0.19-0.93). In order to understand parameters that might contribute to intrinsic radiosensitivity, we evaluated the relationships of cellular radiosensitivity with basic cellular characteristics of the cell lines. There was no significant correlation of SF2 with S-phase fraction, doubling time, chromosome number, ploidy, or number of metacentric chromosomes, while there was a statistically significant correlation between SF2 and plating efficiency. Next, we selected the five most radiosensitive cell lines as the radiosensitive group and the five most radioresistant cell lines as the radioresistant group. Then, we evaluated known parameters for cell killing by ionizing radiation, including radiation-induced DNA double strand break (DSB) repair and apoptosis, in the radiosensitive group as compared to the radioresistant group. High levels of residual γ-H2AX foci at the sites of DSBs were present in the four out of the five radiosensitive canine cancer cell lines. Our studies suggested that substantial differences in intrinsic radiosensitivity exist in canine cancer cell lines, and radiation-induced DSB repair was related to radiosensitivity, which is consistent with previous human studies. These data may assist further investigations

  10. Pressure-Induced Phase Transformation, Reversible Amorphization, and Anomalous Visible Light Response in Organolead Bromide Perovskite.

    PubMed

    Wang, Yonggang; Lü, Xujie; Yang, Wenge; Wen, Ting; Yang, Liuxiang; Ren, Xiangting; Wang, Lin; Lin, Zheshuai; Zhao, Yusheng

    2015-09-01

    Hydrostatic pressure, as an alternative of chemical pressure to tune the crystal structure and physical properties, is a significant technique for novel function material design and fundamental research. In this article, we report the phase stability and visible light response of the organolead bromide perovskite, CH3NH3PbBr3 (MAPbBr3), under hydrostatic pressure up to 34 GPa at room temperature. Two phase transformations below 2 GPa (from Pm3̅m to Im3̅, then to Pnma) and a reversible amorphization starting from about 2 GPa were observed, which could be attributed to the tilting of PbBr6 octahedra and destroying of long-range ordering of MA cations, respectively. The visible light response of MAPbBr3 to pressure was studied by in situ photoluminescence, electric resistance, photocurrent measurements and first-principle simulations. The anomalous band gap evolution during compression with red-shift followed by blue-shift is explained by the competition between compression effect and pressure-induced amorphization. Along with the amorphization process accomplished around 25 GPa, the resistance increased by 5 orders of magnitude while the system still maintains its semiconductor characteristics and considerable response to the visible light irradiation. Our results not only show that hydrostatic pressure may provide an applicable tool for the organohalide perovskites based photovoltaic device functioning as switcher or controller, but also shed light on the exploration of more amorphous organometal composites as potential light absorber. PMID:26284441

  11. Serum Profiling of Rat Dermal Exposure to JP-8 Fuel Reveals an Acute-Phase Response.

    PubMed

    Larabee, Jason L; Hocker, James R; Cheung, John Y; Gallucci, Randle M; Hanas, Jay S

    2008-01-01

    ABSTRACT Dermal exposure to JP-8 petroleum jet fuel leads to toxicological responses in humans and rodents. Serum profiling is a molecular analysis of changes in the levels of serum proteins and other molecules in response to changes in physiology. This present study utilizes serum profiling approaches to examine biomolecular changes in the sera of rats exposed to dermal applications of JP-8 (jet propulsion fuel-8). Using gel electrophoresis and electrospray ionization (ESI) mass spectrometry (MS), levels of serum proteins as well as low-mass constituents were found to change after dermal exposures to JP-8. The serum protein levels altered included the acute-phase response proteins haptoglobin, ceruloplasmin, alpha(1)-inhibitor III, and apolipoprotein A-IV. Haptoglobin levels increased after a 1-day JP-8 dermal exposure and continued to increase through 7 days of exposure. Ceruloplasmin levels increased after 5 days of exposure. Serum alpha(1)-inhibitor III was reduced after a 1-day exposure and the depletion continued after 7 days of exposure. Apolipoprotein A-IV increased after a 1-day exposure and then returned to basal levels after 3- and 5-day exposures of JP-8. Levels of the acute-phase protein alpha(2)-macroglobulin were found to not vary over these time course studies. Using ESI-MS analysis directly on the sera from rats exposed to dermal JP-8, low-mass sera constituents were found to correlate with control (acetone) or JP-8 exposure. PMID:20020890

  12. Cyclin E Is Stabilized in Response to Replication Fork Barriers Leading to Prolonged S Phase Arrest*

    PubMed Central

    Lu, Xiaoyan; Liu, Jia; Legerski, Randy J.

    2009-01-01

    Cyclin E is a regulator of cyclin-dependent protein kinases (Cdks) and is involved in mediating the cell cycle transition from G1 to S phase. Here, we describe a novel function for cyclin E in the long term maintenance of checkpoint arrest in response to replication barriers. Exposure of cells to mitomycin C or UV irradiation, but not ionizing radiation, induces stabilization of cyclin E. Stabilization of cyclin E reduces the activity of Cdk2-cyclin A, resulting in a slowing of S phase progression and arrest. In addition, cyclin E is shown to be required for stabilization of Cdc6, which is required for activation of Chk1 and the replication checkpoint pathway. Furthermore, the stabilization of cyclin E in response to replication fork barriers depends on ATR, but not Nbs1 or Chk1. These results indicate that in addition to its well studied role in promoting cell cycle progression, cyclin E also has a role in regulating cell cycle arrest in response to DNA damage. PMID:19812034

  13. Elevated transcription of the p53 gene in early S-phase leads to a rapid DNA-damage response during S-phase of the cell cycle.

    PubMed

    Takahashi, Paula; Polson, Amanda; Reisman, David

    2011-09-01

    p53 induces the transcription of genes that negatively regulate progression of the cell cycle in response to DNA damage or other cellular stressors, and thus participates in maintaining genome stability. Under stress conditions, p53 must be activated to prohibit the replication of cells containing damaged DNA. However, in normal, non-stressed cells, p53 activity must be inhibited. Previous studies have demonstrated that p53 transcription is activated before or during early S-phase in cells progressing from G(0)/G(1) into S-phase. Since this is not what would be predicted from a gene involved in growth arrest and apoptosis, in this study, we provide evidence that this induction occurs to provide sufficient p53 mRNA to ensure a rapid response to DNA damage before exiting S-phase. When comparing exponentially growing Swiss3T3 cells to those synchronized to enter S-phase simultaneously and treated with the DNA damaging agent camptothecin, we found that with cells in S-phase, p53 protein levels increased earlier, Bax and p21 transcription was activated earlier and to a greater extent and apoptosis occurred earlier and to a greater extent. These findings are consistent with p53 transcription being induced in S-phase to provide for a rapid DNA-damage response during S-phase of the cell cycle. PMID:21710255

  14. Mitochondrial and Chloroplast Stress Responses Are Modulated in Distinct Touch and Chemical Inhibition Phases1[OPEN

    PubMed Central

    Ivanova, Aneta; Millar, A. Harvey; Whelan, James

    2016-01-01

    Previous studies have identified a range of transcription factors that modulate retrograde regulation of mitochondrial and chloroplast functions in Arabidopsis (Arabidopsis thaliana). However, the relative importance of these regulators and whether they act downstream of separate or overlapping signaling cascades is still unclear. Here, we demonstrate that multiple stress-related signaling pathways, with distinct kinetic signatures, converge on overlapping gene sets involved in energy organelle function. The transcription factor ANAC017 is almost solely responsible for transcript induction of marker genes around 3 to 6 h after chemical inhibition of organelle function and is a key regulator of mitochondrial and specific types of chloroplast retrograde signaling. However, an independent and highly transient gene expression phase, initiated within 10 to 30 min after treatment, also targets energy organelle functions, and is related to touch and wounding responses. Metabolite analysis demonstrates that this early response is concurrent with rapid changes in tricarboxylic acid cycle intermediates and large changes in transcript abundance of genes encoding mitochondrial dicarboxylate carrier proteins. It was further demonstrated that transcription factors AtWRKY15 and AtWRKY40 have repressive regulatory roles in this touch-responsive gene expression. Together, our results show that several regulatory systems can independently affect energy organelle function in response to stress, providing different means to exert operational control. PMID:27208304

  15. Impact of Imatinib Adherence on the Cytogenetic Response in Pediatric Chronic Myeloid Leukemia - Chronic Phase.

    PubMed

    Ganta, Ranga Raman; Nasaka, Srividya; Gundeti, Sadashivudu

    2016-09-01

    The authors aimed to study the impact of adherence to imatinib during initial 6 mo on the cytogenetic response in pediatric chronic myeloid leukemia - chronic phase (CML CP). The hospital records of pediatric CML patients (age ≤18 y) from 2009 through 2012, were analyzed retrospectively for the drug adherence and cytogenetic response (CyR) at 6 mo. Forty eight children were analyzed, with the median age of 13 y (range 5-18) and slight male preponderance (M:F- 1.18:1). Sokal scores were low, intermediate and high in 14 (29.3 %), 26 (54.1 %), 8 (16.6 %) children respectively. Only a little more than half of the children were adherent (58 %). At the end of 6 mo, complete cytogenetic response (CCyR) was achieved by 78.5 % of adherent children as compared to 5 % of non-adherent children. Majority (80 %) of the non-adherent children had only a partial cytogenetic response (PCyR). Therefore, it is concluded that most of the adherent children had optimal cytogenetic response at the end of 6 mo and majority of those in the non-adherent group did not attain it. PMID:26843266

  16. The design of a linear phase superconducting filter with quasi-elliptic response

    NASA Astrophysics Data System (ADS)

    Zuo, Tao; Yan, Shaolin; Zhao, Xinjie; Yue, Hongwei; Xie, Qinglian; Fang, Lan

    2008-06-01

    This paper presents the design of a linear phase superconducting filter with quasi-elliptic response. The coupling structure of the filter contains two trisections and one quadruplet. The two trisections are applied to generate two independent transmission zeros for high selectivity and are realized by meandered open-loop microstrip resonators; the quadruplet is applied for phase equalization and realized by four novel L-shaped microstrip resonators. The filter is designed at 1950 MHz with a bandwidth of 20 MHz. It is fabricated on a LaAlO3 wafer with double-coated Tl2Ba2CaCu2O8 films. The filter shows good selectivity together with flat group delay over 80% of the passband both in the simulation and measurements.

  17. Learning intrinsic excitability in medium spiny neurons

    PubMed Central

    Scheler, Gabriele

    2014-01-01

    We present an unsupervised, local activation-dependent learning rule for intrinsic plasticity (IP) which affects the composition of ion channel conductances for single neurons in a use-dependent way. We use a single-compartment conductance-based model for medium spiny striatal neurons in order to show the effects of parameterization of individual ion channels on the neuronal membrane potential-curent relationship (activation function). We show that parameter changes within the physiological ranges are sufficient to create an ensemble of neurons with significantly different activation functions. We emphasize that the effects of intrinsic neuronal modulation on spiking behavior require a distributed mode of synaptic input and can be eliminated by strongly correlated input. We show how modulation and adaptivity in ion channel conductances can be utilized to store patterns without an additional contribution by synaptic plasticity (SP). The adaptation of the spike response may result in either "positive" or "negative" pattern learning. However, read-out of stored information depends on a distributed pattern of synaptic activity to let intrinsic modulation determine spike response. We briefly discuss the implications of this conditional memory on learning and addiction. PMID:25520776

  18. [Responsibilities of clinical pharmacology in the early phase of drug development].

    PubMed

    Kuhlmann, J

    2000-05-01

    The path of a new drug from the idea to the product may be divided into 2 phases, namely drug discovery and drug development. Due to the scientific progress new and simple methods could be developed to determine the biological efficacy of a large number of compounds. During the first part of drug development necessary requirements for the first use in man are met by performing preclinical pharmacological, toxicological and pharmacokinetic investigations in the animal and in in-vitro testing. After a first clinical-pharmacological profile of the new substance has been established during phase I on the basis of which a decision for the continuation of the clinical trial is made, the aim of phases II and III is now to answer the important questions of the therapeutic efficacy and tolerability in a large number of patients with the target indication. Due to the continuously increasing time and costs of drug development, drug development should be streamlined combining preclinical and early clinical phases as an exploratory stage and later clinical development as a confirmatory stage. The development and appropriate use of surrogates and models may be helpful to determine drug actions in human and to assist in dose selection as the main requirement for a successful large clinical trial in the confirmatory stage. Identifying the genes responsible for the huge variations in how different patients respond to a drug, in terms of both the product's effectiveness and its side effects, and genotyping patients before including in large clinical trials may prevent selecting the wrong patient population and avoid expensive repetition of these studies. Taking responsibility as the link between research and development gives clinical pharmacology a major opportunity to assume a pivotal role in drug development. To reach this goal, clinical pharmacology must be fully integrated in the whole process of drug development from the candidate selection until the approval. PMID:10851846

  19. [Responsibilities of clinical pharmacology in the early phase of drug development].

    PubMed

    Kuhlmann, J

    1999-05-15

    The path of a new drug from the idea to the product may be divided into 2 phases, namely drug discovery and drug development. Due to the scientific progress new and simple methods could be developed to determine the biological efficacy of a large number of compounds. During the first part of drug development necessary requirements for the first use in man are met by performing preclinical pharmacological, toxicological and pharmacokinetic investigations in the animal and in in-vitro testing. After a first clinical-pharmacological profile of the new substance has been established during phase I on the basis of which a decision for the continuation of the clinical trial is made, the aim of phases II and III is now to answer the important questions of the therapeutic efficacy and tolerability in a large number of patients with the target indication. Due to the continuously increasing time and costs of drug development, drug development should be streamlined combining preclinical and early clinical phases as an exploratory stage and later clinical development as a confirmatory stage. The development and appropriate use of surrogates and models may be helpful to determine drug actions in human and to assist in dose selection as the main requirement for a successful large clinical trial in the confirmatory stage. Identifying the genes responsible for the huge variations in how different patients respond to a drug, in terms of both the product's effectiveness and its side effects, and genotyping patients before including in large clinical trials may prevent selecting the wrong patient population and avoid expensive repetition of these studies. Taking responsibility as the link between research and development gives clinical pharmacology a major opportunity to assume a pivotal role in drug development. To reach this goal, clinical pharmacology must be fully integrated in the whole process of drug development from the candidate selection until the approval. PMID:10408193

  20. Phase Transition of Methane Gas Hydrate and Response of Marine Gas Hydrate Systems to Environmental Changes

    NASA Astrophysics Data System (ADS)

    Xu, W.

    2003-12-01

    Gas hydrates, which contain mostly methane as the gas component in marine sediment, are stable under relatively high pressure and low temperature conditions such as those found along continental margins and permafrost regions. Its stability is mostly controlled by in-situ pressure, temperature and salinity of pore fluid. Environmentally introduced changes in pressure and temperature can affect the stability of gas hydrate in marine sediment. While certain changes may enhance the process of gas hydrate formation, we are much more interested in the resultant dissociation processes, which may contribute to sub-marine slope instability, seafloor sediment failure, formation of mud volcanoes and pock marks, potential vulnerability of engineering structures, and the risk to drilling and production. We have been developing models to quantify phase transition processes of marine gas hydrates and to investigate the response of marine gas hydrate systems to environmental changes. Methane gas hydrate system is considered as a three-component (water, methane, salt) four-phase (liquid, gas, hydrate, halite) system. Pressure, temperature and salinity of pore fluid constrain the stability of gas hydrate and affect phase transition processes via their effects on methane solubility and fluid density and enthalpy. Compared to the great quantity of studies on its stability in the literature, in-depth research on phase transition of gas hydrate is surprisingly much less. A method, which employs pressure, enthalpy, salinity and methane content as independent variables, is developed to calculate phase transition processes of the three-component four-phase system. Temperature, an intensive thermodynamic parameter, is found not sufficient in describing phase transition of gas hydrate. The extensive thermodynamic parameter enthalpy, on the other hand, is found to be sufficient both in calculation of the phase transition processes and in modeling marine gas hydrate systems. Processes

  1. Intrinsically disordered proteins and biomineralization.

    PubMed

    Boskey, Adele L; Villarreal-Ramirez, Eduardo

    2016-01-01

    In vertebrates and invertebrates, biomineralization is controlled by the cell and the proteins they produce. A large number of these proteins are intrinsically disordered, gaining some secondary structure when they interact with their binding partners. These partners include the component ions of the mineral being deposited, the crystals themselves, the template on which the initial crystals form, and other intrinsically disordered proteins and peptides. This review speculates why intrinsically disordered proteins are so important for biomineralization, providing illustrations from the SIBLING (small integrin binding N-glycosylated) proteins and their peptides. It is concluded that the flexible structure, and the ability of the intrinsically disordered proteins to bind to a multitude of surfaces is crucial, but details on the precise-interactions, energetics and kinetics of binding remain to be determined. PMID:26807759

  2. Repeated allergen exposure reduce early phase airway response and leukotriene release despite upregulation of 5-lipoxygenase pathways

    PubMed Central

    2012-01-01

    Background Allergen induced early phase airway response and airway plasma exudation are predominantly mediated by inflammatory mast cell mediators including histamine, cysteinyl leukotrienes (cysLTs) and thromboxane A2 (TXA2). The aim of the present study was to evaluate whether repeated allergen exposure affects early phase airway response to allergen challenge. Methods A trimellitic anhydride (TMA) sensitized guinea pig model was used to investigate the effects of low dose repeated allergen exposure on cholinergic airway responsiveness, early phase airway response and plasma exudation, as well as local airway production of mast cell derived cysteinyl leukotrienes and thromboxane B2 (TXB2) after allergen challenge. Results Repeated low dose allergen exposure increased cholinergic airway responsiveness. In contrast, early phase airway response and plasma exudation in response to a high-dose allergen challenge were strongly attenuated after repeated low dose allergen exposure. Inhibition of the airway response was unspecific to exposed allergen and independent of histamine receptor blocking. Furthermore, a significant reduction of cysteinyl leukotrienes and TXB2 was found in the airways of animals repeatedly exposed to a low dose allergen. However, in vitro stimulation of airway tissue from animals repeatedly exposed to a low dose allergen with arachidonic acid and calcium ionophore (A23187) induced production of cysteinyl leukotrienes and TXB2, suggesting enhanced activity of 5-lipoxygenase and cyclooxygenase pathways. Conclusions The inhibition of the early phase airway response, cysteinyl leukotriene and TXB2 production after repeated allergen exposure may result from unresponsive effector cells. PMID:22439792

  3. Nankai ACORK Tidel Response: Phase Lead/Delay as a Potential Indicator for Fracture Zones?

    NASA Astrophysics Data System (ADS)

    Kinoshita, M.; Kano, Y.

    2014-12-01

    For more than 12 years we have been conducting a continuous monitoring of downhole pore pressures at multiple sub-bottom intervals in ODP Holes 808I and 1173B situated landward and seaward of the deformation front in the Nankai Trough off Cape Muroto. We found that the pressure response to the semi-diurnal ocean tide (M2), both amplitude and phase, gradually changed during the observed period. The M2 amplitudes at most depths in Hole 808I decay as their phase delay (up to 45 degrees), only if the amplitude is larger than ~0.2 of that for the seafloor. On the other hand, we observe an anomalous phase lead (up to -40 degrees) if the relative amplitude is smaller than ~0.2. We hypothesize that the recorded pore pressure is a combination of two components; one with larger amplitudes and phase-delay and the other with small amplitude and phase-lead. The former is interpreted to be caused by a direct communication between sensors and the seafloor through the space of the annulus. It gradually attenuated by the decrease in hydraulic diffusivity around the sensors, as the annulus space is packed off by a gradual collapsing of the formation. After that, we hypothesize that the sensor is in good mechanical/hydrological contact with the formation, and that the latter variation is identical or close to that of formation pressure variation. The mechanism of the latter variation remains enigmatic, but a feasible explanation is the existence of a layer, next to the sensor, with the contrast in fluid bulk modulus, frame bulk modulus, or permeability (Wang and Davis, 1996). At Site 808, numerous small fractures were detected in cores/logs, which can generate such contrast in bulk modulus or permeability. Other causes, such as solid earth tide or thermal expansion/contraction caused by a tidally-induced flow within the casing cannot explain both the amplitude and phase simultaneously. We propose that a tidal response signal can be used to detect local fracture zones or gas

  4. A quantitative model of the phase behavior of recombinant pH-responsive elastin-like polypeptides

    PubMed Central

    MacKay, J. Andrew; Callahan, Daniel J.; FitzGerald, Kelly N.; Chilkoti, Ashutosh

    2010-01-01

    Quantitative models are required to engineer biomaterials with environmentally responsive properties. With this goal in mind, we developed a model that describes the pH dependent phase behavior of a class of stimulus responsive elastin-like polypeptides (ELPs) that undergo reversible phase separation in response to their solution environment. Under isothermal conditions, charged ELPs can undergo phase separation when their charge is neutralized. Optimization of this behavior has been challenging because the pH at which they phase separate, pHt, depends on their composition, molecular weight, concentration, and temperature. To address this problem, we developed a quantitative model to describe the phase behavior of charged ELPs that uses the Henderson-Hasselbalch relationship to describe the effect of side-chain ionization on the phase transition temperature of an ELP. The model was validated with pH-responsive ELPs that contained either acidic (Glu) or basic (His) residues. The phase separation of both ELPs fit this model across a range of pH. These results have important implications for applications of pH-responsive elastin-like polypeptides, because they provide a quantitative model for the rational design of pH responsive polypeptides whose transition can be triggered at a specified pH. PMID:20925333

  5. Effect of Phase on Human Responses to Vertical Whole-Body Vibration and SHOCK—ANALYTICAL Investigation

    NASA Astrophysics Data System (ADS)

    MATSUMOTO, Y.; GRIFFIN, M. J.

    2002-03-01

    The effect of the “phase” on human responses to vertical whole-body vibration and shock has been investigated analytically using alternative methods of predicting subjective responses (using r.m.s., VDV and various frequency weightings). Two types of phase have been investigated: the effect of the relative phase between two frequency components in the input stimulus, and the phase response of the human body. Continuous vibrations and shocks, based on half-sine and one-and-a-half-sine accelerations, each of which had two frequency components, were used as input stimuli. For the continuous vibrations, an effect of relative phase was found for the vibration dose value (VDV) when the ratio between two frequency components was three: about 12% variation in the VDV of the unweighted acceleration was possible by changing the relative phase. The effect of the phase response of the body represented by frequency weightings was most significant when the frequencies of two sinusoidal components were about 3 and 9 Hz. With shocks, the effect of relative phase was observed for all stimuli used. The variation in the r.m.s. acceleration and in the VDV caused by variations in the relative phase varied between 3 and 100%, depending on the nature of stimulus and the frequency weighting. The phase of the frequency weightings had a different effect on the r.m.s. and the VDV.

  6. Ultrafast optical response of the amorphous and crystalline states of the phase change material Ge2Sb2Te5

    NASA Astrophysics Data System (ADS)

    Miller, T. A.; Rudé, M.; Pruneri, V.; Wall, S.

    2016-07-01

    We examine the ultrafast optical response of the crystalline and amorphous phases of the phase change material Ge2Sb2Te5 (GST) below the phase transformation threshold. Simultaneous measurement of the transmissivity and reflectivity of thin film samples yields the time-dependent evolution of the dielectric function for both phases. We then identify how lattice motion and electronic excitation manifest in the dielectric response. The dielectric response of both phases is large but markedly different. At 800 nm, the changes in amorphous GST are well described by the Drude response of the generated photocarriers, whereas the crystalline phase is better described by the depopulation of resonant bonds. We find that the generated coherent phonons have a greater influence in the amorphous phase than the crystalline phase. Furthermore, coherent phonons do not influence resonant bonding. For fluences up to 50% of the transformation threshold, the structure does not exhibit bond softening in either phase, enabling large changes of the optical properties without structural modification.

  7. Intrinsic magnetization of antiferromagnetic textures

    NASA Astrophysics Data System (ADS)

    Tveten, Erlend G.; Müller, Tristan; Linder, Jacob; Brataas, Arne

    2016-03-01

    Antiferromagnets (AFMs) exhibit intrinsic magnetization when the order parameter spatially varies. This intrinsic spin is present even at equilibrium and can be interpreted as a twisting of the homogeneous AFM into a state with a finite spin. Because magnetic moments couple directly to external magnetic fields, the intrinsic magnetization can alter the dynamics of antiferromagnetic textures under such influence. Starting from the discrete Heisenberg model, we derive the continuum limit of the free energy of AFMs in the exchange approximation and explicitly rederive that the spatial variation of the antiferromagnetic order parameter is associated with an intrinsic magnetization density. We calculate the magnetization profile of a domain wall and discuss how the intrinsic magnetization reacts to external forces. We show conclusively, both analytically and numerically, that a spatially inhomogeneous magnetic field can move and control the position of domain walls in AFMs. By comparing our model to a commonly used alternative parametrization procedure for the continuum fields, we show that the physical interpretations of these fields depend critically on the choice of parametrization procedure for the discrete-to-continuous transition. This can explain why a significant amount of recent studies of the dynamics of AFMs, including effective models that describe the motion of antiferromagnetic domain walls, have neglected the intrinsic spin of the textured order parameter.

  8. Instantaneous kinematic phase reflects neuromechanical response to lateral perturbations of running cockroaches.

    PubMed

    Revzen, Shai; Burden, Samuel A; Moore, Talia Y; Mongeau, Jean-Michel; Full, Robert J

    2013-04-01

    Instantaneous kinematic phase calculation allows the development of reduced-order oscillator models useful in generating hypotheses of neuromechanical control. When perturbed, changes in instantaneous kinematic phase and frequency of rhythmic movements can provide details of movement and evidence for neural feedback to a system-level neural oscillator with a time resolution not possible with traditional approaches. We elicited an escape response in cockroaches (Blaberus discoidalis) that ran onto a movable cart accelerated laterally with respect to the animals' motion causing a perturbation. The specific impulse imposed on animals (0.50 [Formula: see text] 0.04 m s[Formula: see text]; mean, SD) was nearly twice their forward speed (0.25 [Formula: see text] 0.06 m s[Formula: see text]. Instantaneous residual phase computed from kinematic phase remained constant for 110 ms after the onset of perturbation, but then decreased representing a decrease in stride frequency. Results from direct muscle action potential recordings supported kinematic phase results in showing that recovery begins with self-stabilizing mechanical feedback followed by neural feedback to an abstracted neural oscillator or central pattern generator. Trials fell into two classes of forward velocity changes, while exhibiting statistically indistinguishable frequency changes. Animals pulled away from the side with front and hind legs of the tripod in stance recovered heading within 300 ms, whereas animals that only had a middle leg of the tripod resisting the pull did not recover within this period. Animals with eight or more legs might be more robust to lateral perturbations than hexapods. PMID:23371006

  9. Induction of hepatocyte lipopolysaccharide binding protein in models of sepsis and the acute-phase response.

    PubMed

    Geller, D A; Kispert, P H; Su, G L; Wang, S C; Di Silvio, M; Tweardy, D J; Billiar, T R; Simmons, R L

    1993-01-01

    Lipopolysaccharide binding protein (LBP) is a serum glycoprotein that complexes with lipopolysaccharide (LPS) to facilitate macrophage response to endotoxin. To determine the conditions that stimulate LBP production in vivo, we measured the induction of LBP in models of inflammation produced by LPS, Corynebacterium parvum, and turpentine injection. Plasma aspartate aminotransferase and alanine aminotransferase concentrations and hepatocyte fibrinogen synthesis were elevated in all models. Northern blot analysis revealed 17-, 14-, and 20-fold upregulation of hepatocyte LBP mRNA following treatment with LPS, C parvum, and turpentine, respectively. Peritoneal macrophage interleukin 6 and tumor necrosis factor production following endotoxin stimulation was augmented by cultured hepatocyte supernatants, suggesting increased LBP synthesis in these groups. The results show that LBP mRNA is induced during hepatic inflammation and suggest that LBP is an acute-phase protein important in regulating the in vivo response to endotoxin. PMID:8418776

  10. Acute-phase protein response in pigs experimentally infected with Haemophilus parasuis.

    PubMed

    Martín de la Fuente, A J; Carpintero, R; Rodríguez Ferri, E F; Alava, M A; Lampreave, F; Gutiérrez Martín, C B

    2010-12-01

    The acute-phase protein (APP) response to an infection caused by Haemophilus parasuis, the etiological agent of Glässer's disease in pigs, was characterized measuring serum concentrations of pig major acute-phase protein (pig MAP), haptoglobin (HPT), C-reactive protein (CRP) and apolipoprotein A-I (ApoA-I) in colostrum-deprived pigs. They were divided into six experimental groups: non-immunized control group (I); immunized with a non-commercial bacterin (II); with an OMP-vaccine (III); with a sublethal dose (IV); and with two commercial bacterins (V and VI). All groups were challenged intratracheally with 5 × 10(9)CFU of H. parasuis 37 days after immunisation. The highest levels of the positive APPs (pig MAP, HPT and CRP) and the lowest levels of the negative APPs (ApoA-I) were observed in the animals that died as a consequence of the infection, both those in the non-immunized and in the immunized groups. However, the surviving animals (all of them in groups II, V and VI, two pigs in group III, and three in group IV) showed a minor variation in APP response, mainly on day 1 post-challenge (p.c.), and then tended to recover the initial values. APP response was still less pronounced in the groups of pigs previously immunized with bacterins. In conclusion, APP response can reflect Glässer-disease ongoing, showing a correlation between the severity and duration of the clinical signs and lesions and the magnitude of changes in the APP levels. PMID:19117607

  11. NRF2 and the Phase II Response in Acute Stress Resistance Induced by Dietary Restriction.

    PubMed

    Hine, Christopher M; Mitchell, James R

    2012-06-19

    Dietary restriction (DR) as a means to increase longevity is well-established in a number of model organisms from yeast to primates. DR also improves metabolic fitness and increases resistance to acute oxidative, carcinogenic and toxicological stressors - benefits with more immediate potential for clinical translation than increased lifespan. While the detailed mechanism of DR action remains unclear, a conceptual framework involving an adaptive, or hormetic response to the stress of nutrient/energy deprivation has been proposed. A key prediction of the hormesis hypothesis of DR is that beneficial adaptations occur in response to an increase in reactive oxygen/nitrogen species (ROS). These ROS may be derived either from increased mitochondrial respiration or increased xenobiotic metabolism in the case of some DR mimetics. This review will focus on the potential role of the redox-sensing transcription factor NF-E2-related factor 2 (NRF2) and its control of the evolutionarily conserved antioxidant/redox cycling and detoxification systems, collectively known as the Phase II response, in the adaptive response to DR. PMID:23505614

  12. Role of chemokines and chemokine receptors in shaping the effector phase of the antitumor immune response.

    PubMed

    Franciszkiewicz, Katarzyna; Boissonnas, Alexandre; Boutet, Marie; Combadière, Christophe; Mami-Chouaib, Fathia

    2012-12-15

    Immune system-mediated eradication of neoplastic cells requires induction of a strong long-lasting antitumor T-cell response. However, generation of tumor-specific effector T cells does not necessarily result in tumor clearance. CTL must first be able to migrate to the tumor site, infiltrate the tumor tissue, and interact with the target to finally trigger effector functions indispensable for tumor destruction. Chemokines are involved in circulation, homing, retention, and activation of immunocompetent cells. Although some of them are known to contribute to tumor growth and metastasis, others are responsible for changes in the tumor microenvironment that lead to extensive infiltration of lymphocytes, resulting in tumor eradication. Given their chemoattractive and activating properties, a role for chemokines in the development of the effector phase of the antitumor immune response has been suggested. Here, we emphasize the role of the chemokine-chemokine receptor network at multiple levels of the T-cell-mediated antitumor immune response. The identification of chemokine-dependent molecular mechanisms implicated in tumor-specific CTL trafficking, retention, and regulation of their in situ effector functions may offer new perspectives for development of innovative immunotherapeutic approaches to cancer treatment. PMID:23222302

  13. NRF2 and the Phase II Response in Acute Stress Resistance Induced by Dietary Restriction

    PubMed Central

    Hine, Christopher M.; Mitchell, James R.

    2013-01-01

    Dietary restriction (DR) as a means to increase longevity is well-established in a number of model organisms from yeast to primates. DR also improves metabolic fitness and increases resistance to acute oxidative, carcinogenic and toxicological stressors - benefits with more immediate potential for clinical translation than increased lifespan. While the detailed mechanism of DR action remains unclear, a conceptual framework involving an adaptive, or hormetic response to the stress of nutrient/energy deprivation has been proposed. A key prediction of the hormesis hypothesis of DR is that beneficial adaptations occur in response to an increase in reactive oxygen/nitrogen species (ROS). These ROS may be derived either from increased mitochondrial respiration or increased xenobiotic metabolism in the case of some DR mimetics. This review will focus on the potential role of the redox-sensing transcription factor NF-E2-related factor 2 (NRF2) and its control of the evolutionarily conserved antioxidant/redox cycling and detoxification systems, collectively known as the Phase II response, in the adaptive response to DR. PMID:23505614

  14. The role of the fluid phase in the viscous response of bovine periodontal ligament.

    PubMed

    Bergomi, Marzio; Cugnoni, Joël; Botsis, John; Belser, Urs C; Anselm Wiskott, H W

    2010-04-19

    The mechanical response of the periodontal ligament (PDL) is complex. This tissue responds as a hyperelastic solid when pulled in tension while demonstrating a viscous behavior under compression. This intricacy is reflected in the tissue's morphology, which comprises fibers, glycosaminoglycans, a jagged interface with the surrounding porous bone and an extensive vascular network. In the present study we offer an analysis of the viscous behavior and the interplay between the fibrous matrix and its fluid phase. Cylindrical specimens comprising layers of dentine, PDL and bone were extracted from bovine first molars and affixed to a tensile-compressive loading machine. The viscous properties of the tissue were analyzed (1) by subjecting the specimens to sinusoidal displacements at various frequencies and (2) by cycling the specimens in 'fully saturated' and in 'partially dry' conditions. Both modes assisted in determining the contribution of the fluid phase to the mechanical response. It was concluded that: (1) PDL showed pseudo-plastic viscous features for cyclic compressive loading, (2) these viscous features essentially resulted from interactions between the porous matrix and unbound fluid content of the tissue. Removing the liquid from the PDL largely eliminates its damping effect in compression. PMID:20185135

  15. Tail biting induces a strong acute phase response and tail-end inflammation in finishing pigs.

    PubMed

    Heinonen, Mari; Orro, Toomas; Kokkonen, Teija; Munsterhjelm, Camilla; Peltoniemi, Olli; Valros, Anna

    2010-06-01

    The extent of inflammation associated with tail biting in finishing pigs was evaluated. Tail histopathology, carcass condemnation and the concentration of three acute phase proteins (APPs), C-reactive protein (CRP), serum amyloid-A (SAA) and haptoglobin (Hp), were examined in 12 tail-bitten and 13 control pigs. The median concentrations of APPs were higher (P<0.01) in bitten (CRP 617.5mg/L, range 80.5-969.9; SAA 128.0mg/L, 6.2-774.4; Hp 2.8g/L, 1.6-3.5) than in control pigs (CRP 65.7mg/L, 28.4-180.4; SAA 6.2mg/L, 6.2-21.4; Hp 1.2g/L, 0.9-1.5). There was a tendency for APP concentrations to rise with the histopathological score but the differences were only statistically significant between some of the scores. Five (42%) bitten cases and one (8%) control pig had partial carcass condemnations owing to abscesses (P=0.07). The results show that tail biting induces an inflammatory response in the tail end leading to an acute phase response and formation of carcass abscesses. PMID:19398209

  16. Phase III Preclinical Trials in Translational Stroke Research: Community Response on Framework and Guidelines.

    PubMed

    Boltze, Johannes; Wagner, Daniel-Christoph; Henninger, Nils; Plesnila, Nikolaus; Ayata, Cenk

    2016-08-01

    The multicenter phase III preclinical trial concept is currently discussed to enhance the predictive value of preclinical stroke research. After public announcement, we collected a community feedback on the concept with emphasis on potential design features and guidelines by an anonymous survey. Response analysis was conducted after plausibility checks by applying qualitative and quantitative measures. Most respondents supported the concept, including the implementation of a centralized steering committee. Based on received feedback, we suggest careful, stepwise implementation and to leave selected competencies and endpoint analysis at the discretion of participating centers. Strict application of quality assurance methods is accepted, but should be harmonized. However, received responses also indicate that the application of particular quality assurance models may require more attention throughout the community. Interestingly, clear and pragmatic preferences were given regarding publication and financing, suggesting the establishing of writing committees similar to large-scale clinical trials and global funding resources for financial support. The broad acceptance among research community encourages phase III preclinical trial implementation. PMID:27297402

  17. Protein synthesis during the initial phase of the temperature-induced bleaching response in Euglena gracilis

    SciTech Connect

    Ortiz, W. )

    1990-05-01

    Growing cultures of photoheterotrophic Euglena gracilis experience an increase in chlorophyll accumulation during the initial phase of the temperature-induced bleaching response suggesting an increase in the synthesis of plastid components at the bleaching temperature of 33{degree}C. A primary goal of this work was to establish whether an increase in the synthesis of plastid proteins accompanies the observed increase in chlorophyll accumulation. In vivo pulse-labeling experiments with ({sup 35}S)sodium sulfate were carried out with cells grown at room temperature or at 33{degree}C. The synthesis of a number of plastid polypeptides of nucleocytoplasmic origin, including some presumably novel polypeptides, increased in cultures treated for 15 hours at 33{degree}C. In contrast, while synthesis of thylakoid proteins by the plastid protein synthesis machinery decreased modestly, synthesis of the large subunit of the enzyme ribulosebisphosphate carboxylase was strongly affected at the elevated temperature. Synthesis of novel plastid-encoded polypeptides was not induced at the bleaching temperature. It is concluded that protein synthesis in plastids declines during the initial phase of the temperature response in Euglena despite an overall increase in cellular protein synthesis and an increase in chlorophyll accumulation per cell.

  18. Responsive Gel-Gel Phase Transitions in Artificially Engineered Protein Hydrogels

    NASA Astrophysics Data System (ADS)

    Olsen, B. D.

    2012-02-01

    Artificially engineered protein hydrogels provide an attractive platform for biomedical materials due to their similarity to components of the native extracellular matrix. Engineering responsive transitions between shear-thinning and tough gel phases in these materials could potentially enable gels that are both shear-thinning and tough to be produced as novel injectable biomaterials. To engineer a gel with such transitions, a triblock copolymer with thermoresponsive polymer endblocks and an artificially engineered protein gel midblock is designed. Temperature is used to trigger a transition from a single network protein hydrogel phase to a double network phase with both protein and block copolymer networks present at different length scales. The thermodynamics of network formation and resulting structural changes are established using small-angle scattering, birefringence, and dynamic scanning calorimetry. The formation of the second network is shown to produce a large, nonlinear increase in the elastic modulus as well as enhancements in creep compliance and toughness. Although the gels show yielding behavior in both the single and double network regimes, a qualitative change in the deformation mechanism is observed due to the structural changes.

  19. Pressure responses of portlandite and H-D isotope effects on pressure-induced phase transitions

    NASA Astrophysics Data System (ADS)

    Iizuka, Riko; Kagi, Hiroyuki; Komatsu, Kazuki; Ushijima, Daichi; Nakano, Satoshi; Sano-Furukawa, Asami; Nagai, Takaya; Yagi, Takehiko

    2011-12-01

    The pressure responses of portlandite and the isotope effect on the phase transition were investigated at room temperature from single-crystal Raman and IR spectra and from powder X-ray diffraction using diamond anvil cells under quasi-hydrostatic conditions in a helium pressure-transmitting medium. Phase transformation and subsequent peak broadening (partial amorphization) observed from the Raman and IR spectra of Ca(OH)2 occurred at lower pressures than those of Ca(OD)2. In contrast, no isotope effect was found on the volume and axial compressions observed from powder X-ray diffraction patterns. X-ray diffraction lines attributable to the high-pressure phase remained up to 28.5 GPa, suggesting no total amorphization in a helium pressure medium within the examined pressure region. These results suggest that the H-D isotope effect is engendered in the local environment surrounding H(D) atoms. Moreover, the ratio of sample-to-methanol-ethanol pressure medium (i.e., packing density) in the sample chamber had a significant effect on the increase in the half widths of the diffraction lines, even at pressures below the hydrostatic limit of the pressure medium.

  20. Flexible designs for phase II comparative clinical trials involving two response variables.

    PubMed

    Bersimis, S; Sachlas, A; Papaioannou, T

    2015-01-30

    The aim of phase II clinical trials is to determine whether an experimental treatment is sufficiently promising and safe to justify further testing. The need for reduced sample size arises naturally in phase II clinical trials owing to both technical and ethical reasons, motivating a significant part of research in the field during recent years, while another significant part of the research effort is aimed at more complex therapeutic schemes that demand the consideration of multiple endpoints to make decisions. In this paper, our attention is restricted to phase II clinical trials in which two treatments are compared with respect to two dependent dichotomous responses proposing some flexible designs. These designs permit the researcher to terminate the clinical trial when high rates of favorable or unfavorable outcomes are observed early enough requiring in this way a small number of patients. From the mathematical point of view, the proposed designs are defined on bivariate sequences of multi-state trials, and the corresponding stopping rules are based on various distributions related to the waiting time until a certain number of events appear in these sequences. The exact distributions of interest, under a unified framework, are studied using the Markov chain embedding technique, which appears to be very useful in clinical trials for the sample size determination. Tables of expected sample size and power are presented. The numerical illustration showed a very good performance for these new designs. PMID:25274584

  1. Intrinsic disorder in transcription factors†

    PubMed Central

    Liu, Jiangang; Perumal, Narayanan B.; Oldfield, Christopher J.; Su, Eric W.; Uversky, Vladimir N.; Dunker, A. Keith

    2008-01-01

    Intrinsic disorder (ID) is highly abundant in eukaryotes, which reflect the greater need for disorder-associated signaling and transcriptional regulation in nucleated cells. Although several well-characterized examples of intrinsically disordered proteins in transcriptional regulation have been reported, no systematic analysis has been reported so far. To test for a general prevalence of intrinsic disorder in transcriptional regulation, we used the Predictor Of Natural Disorder Regions (PONDR) to analyze the abundance of intrinsic disorder in three transcription factor datasets and two control sets. This analysis revealed that from 94.13% to 82.63% of transcription factors posses extended regions of intrinsic disorder, relative to 54.51% and 18.64% of the proteins in two control datasets, which indicates the significant prevalence of intrinsic disorder in transcription factors. This propensity of transcription factors for intrinsic disorder was confirmed by cumulative distribution function analysis and charge-hydropathy plots. The amino acid composition analysis showed that all three transcription factor datasets were substantially depleted in order-promoting residues, and significantly enriched in disorder-promoting residues. Our analysis of the distribution of disorder within the transcription factor datasets revealed that: (a) The AT-hooks and basic regions of transcription factor DNA-binding domains are highly disordered; (b) The degree of disorder in transcription factor activation regions is much higher than that in DNA-binding domains; (c) The degree of disorder is significantly higher in eukaryotic transcription factors than in prokaryotic transcription factors; (d) The level of α-MoRFs (molecular recognition feature) prediction is much higher in transcription factors. Overall, our data reflected the fact that the eukaryotes with well-developed gene transcription machinery require transcription factor flexibility to be more efficient. PMID:16734424

  2. Demand Response Spinning Reserve Demonstration -- Phase 2 Findings from the Summer of 2008

    SciTech Connect

    Eto, Joseph H.; Nelson-Hoffman, Janine; Parker, Eric; Bernier, Clark; Young, Paul; Sheehan, Dave; Kueck, John; Kirby, Brendan

    2009-04-30

    The Demand Response Spinning Reserve project is a pioneering demonstration showing that existing utility load-management assets can provide an important electricity system reliability resource known as spinning reserve. Using aggregated demand-side resources to provide spinning reserve as demonstrated in this project will give grid operators at the California Independent System Operator (CA ISO) and Southern California Edison (SCE) a powerful new tool to improve reliability, prevent rolling blackouts, and lower grid operating costs.In the first phase of this demonstration project, we target marketed SCE?s air-conditioning (AC) load-cycling program, called the Summer Discount Plan (SDP), to customers on a single SCE distribution feederand developed an external website with real-time telemetry for the aggregated loads on this feeder and conducted a large number of short-duration curtailments of participating customers? air-conditioning units to simulate provision of spinning reserve. In this second phase of the demonstration project, we explored four major elements that would be critical for this demonstration to make the transition to a commercial activity:1. We conducted load curtailments within four geographically distinct feeders to determine the transferability of target marketing approaches and better understand the performance of SCE?s load management dispatch system as well as variations in the AC use of SCE?s participating customers;2. We deployed specialized, near-real-time AC monitoring devices to improve our understanding of the aggregated load curtailments we observe on the feeders;3. We integrated information provided by the AC monitoring devices with information from SCE?s load management dispatch system to measure the time required for each step in the curtailment process; and4. We established connectivity with the CA ISO to explore the steps involved in responding to CA ISO-initiated requests for dispatch of spinning reserve.The major findings from

  3. Nature of men and higher animals' response to the lunar phases.

    NASA Astrophysics Data System (ADS)

    Troshichev, Oleg; Vladimir, Vorobeichikov; Viktor, Stepanov; Eduard, Gorshkov

    The Moon impact on the abnormal behavior of men and higher animals was marked during the entire mankind history, but the nature of this effect remained unclear. The popular hypothesis of the tidal influence of the Moon on the living organisms turned out to be incompatible with the contemporary biophysics concepts. In addition, the estimates of the lunar gravity influence on the men organism showed the negligible value of the possible effect. Vorobeichikov et al. [2006] were the first who suggested that the organisms' response to the lunar phases can be linked with the bacillus E.coli inhabiting in the bowels of the living organisms. E.coli belongs to family of enterobacteria, which are the important component of the human body microflora. Bacteria E.coli being sowed in the nutritious medium go in their development through four stages: adjusting, explosive reproducing, stationary, and dieing. The adjusting stage (or lagphase) is the most interesting for researchers, since duration of this phase L (the interval between the sowing time and the onset of the quick, exponential reproduction) is strongly influenced by the external conditions and can vary from standard 3 - 3.5 hours to some minutes. In our experiments the lag-phase L was determined for days of new moon and full moon, and for such exclusive events as the solar and lunar eclipses. The standard quantity of E.coli was sowed in the standard volume of the artificial nutritive. Lag-phase was detected every 1 minute near the key moment and every 15 minutes at other hours. It turned out that lag-phase is reduced to 1.5 hour for new moon, 1 hour for full moon, 0.5 hour for the lunar eclipse and falls to zero for the solar eclipse. In the latter case it took about 10 hours for the lag phase reduction before the eclipse and the lag-phase recovery after the eclipse. In case of a new moon the lag phase reduction lasted about half of hour. Thus, the close was the Moon to the line Sun-Earth, the shorter was lag phase and

  4. Analysis of cardiorespiratory phase coupling and cardiovascular autonomic responses during food ingestion.

    PubMed

    Niizeki, Kyuichi; Saitoh, Tadashi

    2016-05-15

    The present study analyzed whether the phase coherency (λ) of respiratory sinus arrhythmia (RSA) is altered by food ingestion in healthy young subjects. After 5min of resting control, 13 healthy volunteers were asked to eat a solid meal with access to water at their own pace, followed by 5min of the postprandial state. The R-R interval (RRI), beat-to-beat blood pressure (BP), and respiratory activity were recorded using electrocardiography, a Finapres device, and inductance plethysmography, respectively. The stroke volume was calculated by the pulse-contour method from continuous BP measurement, and the cardiac output (CO) was obtained by multiplying the stroke volume by the heart rate. From the oscillatory signals of RSA and respiration, λ was computed; additionally, frequency domain indexes of the heart rate variability (HRV) were calculated using a short-time Fourier transform. A steady-state 3-min resting period (R), food ingestion period (FOOD), and the first 2-min and the last 3-min of the post prandial period were analyzed separately. We also compared the responses to gum chewing (GUM) and water intake (WATER) using the same protocol on separate days. A shortening of RRI and increases in BP and CO were observed in FOOD compared to R, suggesting a shift of sympathovagal balance toward sympathetic activation. Similar responses but smaller magnitudes were observed in the GUM condition, whereas only transient shortening of RRI was observed in the WATER condition. The HRV indexes did not show any significant changes in response to GUM and WATER but sympathovagal balance was shifted in favor of sympathetic dominance in FOOD. λ decreased during all of the conditions. There was a significant negative correlation between λ and the indirect measure of sympathovagal balance. These results suggest that ingestion of food induces enhanced cardiac sympathetic activity and that a phase coherence of RSA could provide a sensitive measure for evaluating the cardiac

  5. Kinesin tail domains are intrinsically disordered.

    PubMed

    Seeger, Mark A; Zhang, Yongbo; Rice, Sarah E

    2012-10-01

    Kinesin motor proteins transport a wide variety of molecular cargoes in a spatially and temporally regulated manner. Kinesin motor domains, which hydrolyze ATP to produce a directed mechanical force along a microtubule, are well conserved throughout the entire superfamily. Outside of the motor domains, kinesin sequences diverge along with their transport functions. The nonmotor regions, particularly the tails, respond to a wide variety of structural and molecular cues that enable kinesins to carry specific cargoes in response to particular cellular signals. Here, we demonstrate that intrinsic disorder is a common structural feature of kinesins. A bioinformatics survey of the full-length sequences of all 43 human kinesins predicts that significant regions of intrinsically disordered residues are present in all kinesins. These regions are concentrated in the nonmotor domains, particularly in the tails and near sites for ligand binding or post-translational modifications. In order to experimentally verify these predictions, we expressed and purified the tail domains of kinesins representing three different families (Kif5B, Kif10, and KifC3). Circular dichroism and NMR spectroscopy experiments demonstrate that the isolated tails are disordered in vitro, yet they retain their functional microtubule-binding activity. On the basis of these results, we propose that intrinsic disorder is a common structural feature that confers functional specificity to kinesins. PMID:22674872

  6. Kinesin Tail Domains Are Intrinsically Disordered

    PubMed Central

    Seeger, Mark A.; Zhang, Yongbo; Rice, Sarah E.

    2012-01-01

    Kinesin motor proteins transport a wide variety of molecular cargoes in a spatially and temporally regulated manner. Kinesin motor domains, which hydrolyze ATP to produce a directed mechanical force along a microtubule, are well conserved throughout the entire superfamily. Outside of the motor domains, kinesin sequences diverge along with their transport functions. The non-motor regions, particularly the tails, respond to a wide variety of structural and molecular cues that enable kinesins to carry specific cargoes in response to particular cellular signals. Here, we demonstrate that intrinsic disorder is a common structural feature of kinesins. A bioinformatics survey of the full-length sequences of all 43 human kinesins predicts that significant regions of intrinsically disordered residues are present in all kinesins. These regions are concentrated in the non-motor domains, particularly in the tails and near sites for ligand binding or post-translational modifications. In order to experimentally verify these predictions, we expressed and purified the tail domains of kinesins representing three different families (Kif5B, Kif10, and KifC3). Circular dichroism (CD) and NMR spectroscopy experiments demonstrate that the isolated tails are disordered in vitro, yet they retain their functional microtubule-binding activity. Based on these results, we propose that intrinsic disorder is a common structural feature that confers functional specificity to kinesins. PMID:22674872

  7. Mutational analysis of acute-phase response factor/Stat3 activation and dimerization.

    PubMed Central

    Sasse, J; Hemmann, U; Schwartz, C; Schniertshauer, U; Heesel, B; Landgraf, C; Schneider-Mergener, J; Heinrich, P C; Horn, F

    1997-01-01

    Signal transducer and transcription (STAT) factors are activated by tyrosine phosphorylation in response to a variety of cytokines, growth factors, and hormones. Tyrosine phosphorylation triggers dimerization and nuclear translocation of these transcription factors. In this study, the functional role of carboxy-terminal portions of the STAT family member acute-phase response factor/Stat3 in activation, dimerization, and transactivating potential was analyzed. We demonstrate that truncation of 55 carboxy-terminal amino acids causes constitutive activation of Stat3 in COS-7 cells, as is known for the Stat3 isoform Stat3beta. By the use of deletion and point mutants, it is shown that both carboxy- and amino-terminal portions of Stat3 are involved in this phenomenon. Dimerization of Stat3 was blocked by point mutations affecting residues both in the vicinity of the tyrosine phosphorylation site (Y705) and more distant from this site, suggesting that multiple interactions are involved in dimer formation. Furthermore, by reporter gene assays we demonstrate that carboxy-terminally truncated Stat3 proteins are incapable of transactivating an interleukin-6-responsive promoter in COS-7 cells. In HepG2 hepatoma cells, however, these truncated Stat3 forms transmit signals from the interleukin-6 signal transducer gp130 equally well as does full-length Stat3. We conclude that, dependent on the cell type, different mechanisms allow Stat3 to regulate target gene transcription either with or without involvement of its putative carboxy-terminal transactivation domain. PMID:9234724

  8. Distinct phosphatases antagonize the p53 response in different phases of the cell cycle.

    PubMed

    Shaltiel, Indra A; Aprelia, Melinda; Saurin, Adrian T; Chowdhury, Dipanjan; Kops, Geert J P L; Voest, Emile E; Medema, René H

    2014-05-20

    The basic machinery that detects DNA damage is the same throughout the cell cycle. Here, we show, in contrast, that reversal of DNA damage responses (DDRs) and recovery are fundamentally different in G1 and G2 phases of the cell cycle. We find that distinct phosphatases are required to counteract the checkpoint response in G1 vs. G2. Whereas WT p53-induced phosphatase 1 (Wip1) promotes recovery in G2-arrested cells by antagonizing p53, it is dispensable for recovery from a G1 arrest. Instead, we identify phosphoprotein phosphatase 4 catalytic subunit (PP4) to be specifically required for cell cycle restart after DNA damage in G1. PP4 dephosphorylates Krüppel-associated box domain-associated protein 1-S473 to repress p53-dependent transcriptional activation of p21 when the DDR is silenced. Taken together, our results show that PP4 and Wip1 are differentially required to counteract the p53-dependent cell cycle arrest in G1 and G2, by antagonizing early or late p53-mediated responses, respectively. PMID:24711418

  9. Acute phase response, inflammation and metabolic syndrome biomarkers of Libby asbestos exposure

    SciTech Connect

    Shannahan, Jonathan H.; Alzate, Oscar; Winnik, Witold M.; Andrews, Debora; Schladweiler, Mette C.; Ghio, Andrew J.; Gavett, Stephen H.; Kodavanti, Urmila P.

    2012-04-15

    Identification of biomarkers assists in the diagnosis of disease and the assessment of health risks from environmental exposures. We hypothesized that rats exposed to Libby amphibole (LA) would present with a unique serum proteomic profile which could help elucidate epidemiologically-relevant biomarkers. In four experiments spanning varied protocols and temporality, healthy (Wistar Kyoto, WKY; and F344) and cardiovascular compromised (CVD) rat models (spontaneously hypertensive, SH; and SH heart failure, SHHF) were intratracheally instilled with saline (control) or LA. Serum biomarkers of cancer, inflammation, metabolic syndrome (MetS), and the acute phase response (APR) were analyzed. All rat strains exhibited acute increases in α-2-macroglobulin, and α1-acid glycoprotein. Among markers of inflammation, lipocalin-2 was induced in WKY, SH and SHHF and osteopontin only in WKY after LA exposure. While rat strain- and age-related changes were apparent in MetS biomarkers, no LA effects were evident. The cancer marker mesothelin was increased only slightly at 1 month in WKY in one of the studies. Quantitative Intact Proteomic profiling of WKY serum at 1 day or 4 weeks after 4 weekly LA instillations indicated no oxidative protein modifications, however APR proteins were significantly increased. Those included serine protease inhibitor, apolipoprotein E, α-2-HS-glycoprotein, t-kininogen 1 and 2, ceruloplasmin, vitamin D binding protein, serum amyloid P, and more 1 day after last LA exposure. All changes were reversible after a short recovery regardless of the acute or long-term exposures. Thus, LA exposure induces an APR and systemic inflammatory biomarkers that could have implications in systemic and pulmonary disease in individuals exposed to LA. -- Highlights: ► Biomarkers of asbestos exposure are required for disease diagnosis. ► Libby amphibole exposure is associated with increased human mortality. ► Libby amphibole increases circulating proteins involved

  10. The distinctive germinal center phase of IgE+ B lymphocytes limits their contribution to the classical memory response

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The mechanisms involved in the maintenance of memory IgE responses are poorly understood, and the role played by germinal center (GC) IgE+ cells in memory responses is particularly unclear. IgE B cell differentiation is characterized by a transient GC phase, a bias towards the plasma cell (PC) fate,...

  11. Phylogeny of major intrinsic proteins.

    PubMed

    Danielson, Jonas A H; Johanson, Urban

    2010-01-01

    Major intrinsic proteins (MIPs) form a large superfamily of proteins that can be divided into different subfamilies and groups according to phylogenetic analyses. Plants encode more MIPs than o ther organisms and se ven subfamilies have been defined, whereofthe Nodulin26-like major intrinsic proteins (NIPs) have been shown to permeate metalloids. In this chapter we review the phylogeny of MIPs in general and especially of the plant MIPs. We also identify bacterial NIP-like MIPs and discuss the evolutionary implications of this finding regarding the origin and ancestral transport specificity of the NIPs. PMID:20666221

  12. The OECD program to validate the rat uterotrophic bioassay. Phase 2: dose-response studies.

    PubMed Central

    Kanno, Jun; Onyon, Lesley; Peddada, Shyamal; Ashby, John; Jacob, Elard; Owens, William

    2003-01-01

    The Organisation for Economic Co-operation and Development has completed phase 2 of an international validation program for the rodent uterotrophic bioassay. The purpose of the validation program was to demonstrate the performance of two versions of the uterotrophic bioassay, the immature female rat and the adult ovariectomized rat, in four standardized protocols. This article reports the dose-response studies of the validation program; the coded single-dose studies are reported in an accompanying paper. The dose-response study design used five selected weak estrogen agonists, bisphenol A, genistein, methoxychlor, nonylphenol, and o,p -DDT. These weak agonists were administered in a prescribed series of doses to measure the performance and reproducibility of the protocols among the participating laboratories. All protocols successfully detected increases in uterine weights when the weak agonists were administered. Within each protocol, there was good agreement and reproducibility of the dose response among laboratories with each substance. Substance-specific variations were observed in the influence of the route of administration on the uterine response, the potency as related to the dose producing the first statistically significant increase in uterine weights, and the maximum increase in uterine weight. Substantive performance differences were not observed between the uterotrophic bioassay versions or among the standardized protocols, and these were judged to be qualitatively equivalent. It is noteworthy that these results were reproducible under a variety of different experimental conditions (e.g., animal strain, diet, housing, bedding, vehicle, animal age), indicating that the bioassay's performance as a screen is robust. In conclusion, both the intact, immature, and adult OVX versions, and all protocols appear to be reproducible and transferable across laboratories and are able to detect weak estrogen agonists. PMID:12948896

  13. Regulation of serum amyloid A protein expression during the acute-phase response.

    PubMed Central

    Jensen, L E; Whitehead, A S

    1998-01-01

    The acute-phase (AP) serum amyloid A proteins (A-SAA) are multifunctional apolipoproteins which are involved in cholesterol transport and metabolism, and in modulating numerous immunological responses during inflammation and the AP response to infection, trauma or stress. During the AP response the hepatic biosynthesis of A-SAA is up-regulated by pro-inflammatory cytokines, and circulating concentrations can increase by up to 1000-fold. Chronically elevated A-SAA concentrations are a prerequisite for the pathogenesis of secondary amyloidosis, a progressive and fatal disease characterized by the deposition in major organs of insoluble plaques composed principally of proteolytically cleaved A-SAA, and may also contribute to physiological processes that lead to atherosclerosis. There is therefore a requirement for both positive and negative control mechanisms that permit the rapid induction of A-SAA expression until it has fulfilled its host-protective function(s) and subsequently ensure that its expression can be rapidly returned to baseline. These mechanisms include modulation of promoter activity involving, for example, the inducer nuclear factor kappaB (NF-kappaB) and its inhibitor IkappaB, up-regulatory transcription factors of the nuclear factor for interleukin-6 (NF-IL6) family and transcriptional repressors such as yin and yang 1 (YY1). Post-transcriptional modulation involving changes in mRNA stability and translation efficiency permit further up- and down-regulatory control of A-SAA protein synthesis to be achieved. In the later stages of the AP response, A-SAA expression is effectively down-regulated via the increased production of cytokine antagonists such as the interleukin-1 receptor antagonist (IL-1Ra) and of soluble cytokine receptors, resulting in less signal transduction driven by pro-inflammatory cytokines. PMID:9729453

  14. Intrinsic and Extrinsic Motivation for Smoking Cessation.

    ERIC Educational Resources Information Center

    Curry, Susan; And Others

    1990-01-01

    Evaluated intrinsic-extrinsic model of motivation for smoking cessation using two samples (Ns=1,217 and 151) of smokers. Analysis on Reasons for Quitting scale supported intrinsic-extrinsic motivation distinction, defining four-factor model with two intrinsic and two extrinsic dimensions. Found that smokers with higher levels of intrinsic relative…

  15. Adaptation to steady light by intrinsically photosensitive retinal ganglion cells.

    PubMed

    Do, Michael Tri Hoang; Yau, King-Wai

    2013-04-30

    Intrinsically photosensitive retinal ganglion cells (ipRGCs) are recently discovered photoreceptors in the mammalian eye. These photoreceptors mediate primarily nonimage visual functions, such as pupillary light reflex and circadian photoentrainment, which are generally expected to respond to the absolute light intensity. The classical rod and cone photoreceptors, on the other hand, mediate image vision by signaling contrast, accomplished by adaptation to light. Experiments by others have indicated that the ipRGCs do, in fact, light-adapt. We found the same but, in addition, have now quantified this light adaptation for the M1 ipRGC subtype. Interestingly, in incremental-flash-on-background experiments, the ipRGC's receptor current showed a flash sensitivity that adapted in background light according to the Weber-Fechner relation, well known to describe the adaptation behavior of rods and cones. Part of this light adaptation by ipRGCs appeared to be triggered by a Ca(2+) influx, in that the flash response elicited in the absence of extracellular Ca(2+) showed a normal rising phase but a slower decay phase, resulting in longer time to peak and higher sensitivity. There is, additionally, a prominent Ca(2+)-independent component of light adaptation not typically seen in rods and cones or in invertebrate rhabdomeric photoreceptors. PMID:23589882

  16. Linear response of light deformed nuclei investigated by self-consistent quasiparticle random-phase approximation

    SciTech Connect

    Losa, C.; Doessing, T.; Pastore, A.; Vigezzi, E.; Broglia, R. A.

    2010-06-15

    We present a calculation of the properties of vibrational states in deformed, axially-symmetric even-even nuclei, within the framework of a fully self-consistent quasiparticle random phase approximation (QRPA). The same Skyrme energy density and density-dependent pairing functionals are used to calculate the mean field and the residual interaction in the particle-hole and particle-particle channels. We have tested our software in the case of spherical nuclei against fully self-consistent calculations published in the literature, finding excellent agreement. We investigate the consequences of neglecting the spin-orbit and Coulomb residual interactions in QRPA. Furthermore we discuss the improvement obtained in the QRPA result associated with the removal of spurious modes. Isoscalar and isovector responses in the deformed {sup 24-26}Mg, {sup 34}Mg isotopes are presented and compared to experimental findings.

  17. Bending the curve: force health protection during the insertion phase of the Ebola outbreak response.

    PubMed

    Bailey, Mark S; Beaton, K; Bowley, D; Eardley, W; Hunt, P; Johnson, S; Round, J; Tarmey, N T; Williams, A

    2016-06-01

    After >10 years of enduring operations in Iraq and Afghanistan, Defence Strategic Direction is returning to a contingency posture. As the first post-Afghanistan operation, in September 2014, a UK Joint Inter-Agency Task Force deployed to Sierra Leone in response to the Ebola virus disease (EVD) epidemic in West Africa. The aims were expanding treatment capacity, assisting with training and supporting host nation resilience. The insertion phase of this deployment created a unique set of challenges for force health protection. In addition to the considerable risk of tropical disease and trauma, deployed personnel faced the risks of working in an EVD epidemic. This report explores how deployed medical assets overcame the difficulties of mounting a short-notice contingent operation in a region of the world with inherent major climatic and health challenges. PMID:26036821

  18. NASA Environmentally Responsible Aviation Projects Propulsion Technology Phase I Overview and Highlights of Accomplishments

    NASA Technical Reports Server (NTRS)

    Suder, Kenneth L.; Delaat, John C.

    2012-01-01

    The NASA Environmentally Responsible Aviation (ERA) Project is focused on developing and demonstrating integrated systems technologies to TRL 4-6 by 2020 that enable reduced fuel burn, emissions, and noise for futuristic air vehicles. The specific goals aim to simultaneously reduce fuel burn by 50%, reduce Landing and Take-off Nitrous Oxides emissions by 75% relative to the CAEP 6 guidelines, and reduce cumulative noise by 42 Decibels relative to the Stage 4 guidelines. These goals apply to the integrated vehicle and propulsion system and are based on a reference mission of 3000nm flight of a Boeing 777-200 with GE90 engines. This paper will focus primarily on the ERA propulsion technology portfolio, which consists of advanced combustion, propulsor, and core technologies to enable these integrated air vehicle systems goals. An overview of the ERA propulsion technologies will be described and highlights of the results obtained during the first phase of ERA will be presented.

  19. Proteomics analysis of urine reveals acute phase response proteins as candidate diagnostic biomarkers for prostate cancer.

    PubMed

    Davalieva, Katarina; Kiprijanovska, Sanja; Komina, Selim; Petrusevska, Gordana; Zografska, Natasha Chokrevska; Polenakovic, Momir

    2015-01-01

    Despite the overall success of prostate specific antigen (PSA) in screening and detection of prostate cancer (PCa), its use has been limited due to the lack of specificity. The principal driving goal currently within PCa research is to identify non-invasive biomarker(s) for early detection of aggressive tumors with greater sensitivity and specificity than PSA. In this study, we focused on identification of non-invasive biomarkers in urine with higher specificity than PSA. We tested urine samples from PCa and benign prostatic hyperplasia (BPH) patients by 2-D DIGE coupled with MS and bioinformatics analysis. Statistically significant (p < 0.05), 1.8 fold variation or more in abundance, showed 41 spots, corresponding to 23 proteins. The Ingenuity Pathway Analysis showed significant association with the Acute Phase Response Signaling pathway. Nine proteins with differential abundances were included in this pathway: AMBP, APOA1, FGA, FGG, HP, ITIH4, SERPINA1, TF and TTR. The expression pattern of 4 acute phase response proteins differed from the defined expression in the canonical pathway. The urine levels of TF, AMPB and HP were measured by immunoturbidimetry in an independent validation set. The concentration of AMPB in urine was significantly higher in PCa while levels of TF and HP were opposite (p < 0.05). The AUC for the individual proteins ranged from 0.723 to 0.754. The combination of HP and AMBP yielded the highest accuracy (AUC = 0.848), greater than PSA. The proposed biomarker set is quickly quantifiable and economical with potential to improve the sensitivity and specificity of PCa detection. PMID:25653573

  20. Aptamer-based Proteomic Signature of Intensive Phase Treatment Response in Pulmonary Tuberculosis

    PubMed Central

    Nahid, Payam; Bliven-Sizemore, Erin; Jarlsberg, Leah G.; Mary, A; Groote, De; Johnson, John L.; Muzanyi, Grace; Engle, Melissa; Weiner, Marc; Janjic, Nebojsa; Sterling, David G.; Ochsner, Urs A.

    2014-01-01

    Background New drug regimens of greater efficacy and shorter duration are needed for tuberculosis (TB) treatment. The identification of accurate, quantitative, non-culture based markers of treatment response would improve the efficiency of Phase 2 TB drug testing. Methods In an unbiased biomarker discovery approach, we applied a highly multiplexed, aptamer-based, proteomic technology to analyze serum samples collected at baseline and after 8 weeks of treatment from 39 patients with pulmonary TB from Kampala, Uganda enrolled in a Centers for Disease Control and Prevention (CDC) TB Trials Consortium Phase 2B treatment trial. Results We identified protein expression differences associated with 8-week culture status, including Coagulation Factor V, SAA, XPNPEP1, PSME1, IL-11 Rα, HSP70, Galectin-8, α2-Antiplasmin, ECM1, YES, IGFBP-1, CATZ, BGN, LYNB, and IL-7. Markers noted to have differential changes between responders and slow-responders included nectin-like protein 2, EphA1 (Ephrin type-A receptor 1), gp130, CNDP1, TGF-b RIII, MRC2, ADAM9, and CDON. A logistic regression model combining markers associated with 8-week culture status revealed an ROC curve with AUC=0.96, sensitivity=0.95 and specificity=0.90. Additional markers showed differential changes between responders and slow-responders (nectin-like protein), or correlated with time-to-culture-conversion (KLRK1). Conclusions Serum proteins involved in the coagulation cascade, neutrophil activity, immunity, inflammation, and tissue remodeling were found to be associated with TB treatment response. A quantitative, non-culture based, five-marker signature predictive of 8-week culture status was identified in this pilot study. PMID:24629635

  1. Structure, phases, and mechanical response of Ti-alloy bioactive glass composite coatings.

    PubMed

    Nelson, G M; Nychka, J A; McDonald, A G

    2014-03-01

    Porous titanium alloy-bioactive glass composite coatings were manufactured via the flame spray deposition process. The porous coatings, targeted for orthodontic and bone-fixation applications, were made from bioactive glass (45S5) powder blended with either commercially pure titanium (Cp-Ti) or Ti-6Al-4V alloy powder. Two sets of spray conditions, two metallic particle size distributions, and two glass particle size distributions were used for this study. Negative control coatings consisting of pure Ti-6Al-4V alloy or Cp-Ti were sprayed under both conditions. The as-sprayed coatings were characterized through quantitative optical cross-sectional metallography, X-ray diffraction (XRD), and ASTM Standard C633 tensile adhesion testing. Determination of the porosity and glassy phase distribution was achieved by using image analysis in accordance with ASTM Standard E2109. Theoretical thermodynamic and heat transfer modeling was conducted to explain experimental observations. Thermodynamic modeling was performed to estimate the flame temperature and chemical environment for each spray condition and a lumped capacitance heat transfer model was developed to estimate the temperatures attained by each particle. These models were used to establish trends among the choice of alloy, spray condition, and particle size distribution. The deposition parameters, alloy composition, and alteration of the feedstock powder size distribution had a significant effect on the coating microstructure, porosity, phases present, mechanical response, and theoretical particle temperatures that were attained. The most promising coatings were the Ti-6Al-4V-based composite coatings, which had bond strength of 20±2MPa (n=5) and received reinforcement and strengthening from the inclusion of a glassy phase. It was shown that the use of the Ti-6Al-4V-bioactive glass composite coatings may be a superior choice due to the possible osteoproductivity from the bioactive glass, the potential ability to

  2. Signatures of topological phase transition in 3 d topological insulators from dynamical axion response

    NASA Astrophysics Data System (ADS)

    Makhfudz, Imam

    2016-04-01

    Axion electrodynamics, first proposed in the context of particle physics, manifests itself in condensed matter physics in the topological field theory description of 3 d topological insulators and gives rise to magnetoelectric effect, where applying magnetic (electric) field B (E ) induces polarization (magnetization) p (m ) . We use linear response theory to study the associated topological current using the Fu-Kane-Mele model of 3 d topological insulators in the presence of time-dependent uniform weak magnetic field. By computing the dynamical current susceptibility χij jpjp(ω ) , we discover from its static limit an `order parameter' of the topological phase transition between weak topological (or ordinary) insulator and strong topological insulator, found to be continuous. The χij jpjp(ω ) shows a sign-changing singularity at a critical frequency with suppressed strength in the topological insulating state. Our results can be verified in current noise experiment on 3 d TI candidate materials for the detection of such topological phase transition.

  3. Spatial Reasoning With Multiple Intrinsic Frames of Reference

    PubMed Central

    Tamborello, Franklin P; Sun, Yanlong; Wang, Hongbin

    2016-01-01

    Establishing and updating spatial relationships between objects in the environment is vital to maintaining situation awareness and supporting many socio-spatial tasks. In a complex environment, people often need to utilize multiple reference systems that are intrinsic to different objects (intrinsic frame of reference, IFOR), but these IFORs may conflict with each other in one or more ways. Current spatial cognition theories do not adequately address how people handle multi-IFOR reasoning problems. Two experiments manipulated relative orientations of two task-relevant objects with intrinsic axes of orientation as well as their relative task salience. Response times (RTs) decreased with increasing salience of the targeted IFOR. In addition, RTs increased as a consequence of intrinsic orientation conflict, but not by amount of orientation difference. The results suggest that people encounter difficulties when they have to process two conflicting IFOR representations, and that they seem to prioritize processing of each IFOR by salience. PMID:21768066

  4. Reading: Intrinsic versus Extrinsic Motivation.

    ERIC Educational Resources Information Center

    Ediger, Marlow

    Much debate centers on motivating student in reading achievement. Should students feel motivated from within (intrinsic motivation), or is it better to have extrinsic motivation whereby external stimuli are used to help learners achieve optimally in reading? This paper aims to analyze the two points of view about motivating students in reading…

  5. Intrinsic Motivation in Physical Education

    ERIC Educational Resources Information Center

    Davies, Benjamin; Nambiar, Nathan; Hemphill, Caroline; Devietti, Elizabeth; Massengale, Alexandra; McCredie, Patrick

    2015-01-01

    This article describes ways in which educators can use Harter's perceived competence motivation theory, the achievement goal theory, and self-determination theory to develop students' intrinsic motivation to maintain physical fitness, as demonstrated by the Sound Body Sound Mind curriculum and proven effective by the 2013 University of…

  6. Anti-CD163-dexamethasone conjugate inhibits the acute phase response to lipopolysaccharide in rats

    PubMed Central

    Thomsen, Karen Louise; Møller, Holger Jon; Graversen, Jonas Heilskov; Magnusson, Nils E; Moestrup, Søren K; Vilstrup, Hendrik; Grønbæk, Henning

    2016-01-01

    AIM: To study the effect of a new anti-CD163-dexamethasone conjugate targeting activated macrophages on the hepatic acute phase response in rats. METHODS: Wistar rats were injected intravenous with either the CD163 targeted dexamethasone-conjugate (0.02 mg/kg) or free dexamethasone (0.02 or 1 mg/kg) 24 h prior to lipopolysaccharide (LPS) (2.5 mg/kg intraperitoneal). We measured plasma concentrations of tumour necrosis factor-α (TNF-α) and interleukin 6 (IL-6) 2 h post-LPS and liver mRNAs and serum concentrations of the rat acute phase protein α-2-macroglobulin (α-2-M) 24 h after LPS. Also, plasma concentrations of alanine aminotransferase and bilirubin were measured at termination of the study. Spleen weight served as an indicator of systemic steroid effects. RESULTS: The conjugate halved the α-2-M liver mRNA (3.3 ± 0.6 vs 6.8 ± 1.1, P < 0.01) and serum protein (201 ± 48 μg/mL vs 389 ± 67 μg/mL, P = 0.04) after LPS compared to low dose dexamethasone treated animals, while none of the free dexamethasone doses had an effect on liver mRNA or serum levels of α-2-M. Also, the conjugate reduced TNF-α (7208 ± 1977 pg/mL vs 21583 ± 7117 pg/mL, P = 0.03) and IL-6 (15685 ± 3779 pg/mL vs 25715 ± 4036 pg/mL, P = 0.03) compared to the low dose dexamethasone. The high dose dexamethasone dose decreased the spleen weight (421 ± 11 mg vs 465 ± 12 mg, P < 0.05) compared to controls, an effect not seen in any other group. CONCLUSION: Low-dose anti-CD163-dexamethasone conjugate effectively decreased the hepatic acute phase response to LPS. This indicates an anti-inflammatory potential of the conjugate in vivo. PMID:27330681

  7. Chelation efficacy and erythroid response during deferasirox treatment in patients with myeloproliferative neoplasms in fibrotic phase.

    PubMed

    Latagliata, Roberto; Montagna, Chiara; Porrini, Raffaele; Di Veroli, Ambra; Leonetti, Sabrina Crescenzi; Niscola, Pasquale; Ciccone, Fabrizio; Spadea, Antonio; Breccia, Massimo; Maurillo, Luca; Rago, Angela; Spirito, Francesca; Cedrone, Michele; De Muro, Marianna; Montanaro, Marco; Andriani, Alessandro; Bagnato, Antonino; Montefusco, Enrico; Alimena, Giuliana

    2016-06-01

    At present, very few data are available on deferasirox (DFX) in the treatment of patients with Philadelphia-negative myeloproliferative neoplasms in fibrotic phase (FP-MPN) and transfusion dependence. To address this issue, a retrospective analysis of 28 patients (22 male and 6 female) with FP-MPN and iron overload secondary to transfusion dependence was performed, based on patients enrolled in the database of our regional cooperative group who received treatment with DFX. DFX was started after a median interval from diagnosis of 12.8 months (IR 7.1-43.1) with median ferritin values of 1415 ng/mL (IR 1168-1768). Extra-hematological toxicity was reported in 16 of 28 patients (57.1%), but only two patients discontinued treatment due to toxicity. Among 26 patients evaluable for response (≥6 months of treatment), after a median treatment period of 15.4 months (IR 8.1-22.3), 11 patients (42.3%) achieved a stable and consistent reduction in ferritin levels <1000 ng/mL. As for hematological improvement, 6 of 26 patients (23%) showed a persistent (>3 months) rise of Hb levels >1.5 g/dL, with disappearance of transfusion dependence in four cases. Treatment with DFX is feasible and effective in FP-MPN with iron overload. Moreover, in this setting, an erythroid response can occur in a significant proportion of patients. PMID:26277477

  8. Peripherally restricted acute phase response to a viral mimic alters hippocampal gene expression.

    PubMed

    Michalovicz, Lindsay T; Konat, Gregory W

    2014-03-01

    We have previously shown that peripherally restricted acute phase response (APR) elicited by intraperitoneal (i.p.) injection of a viral mimic, polyinosinic-polycytidylic acid (PIC), renders the brain hypersusceptible to excitotoxic insult as seen from profoundly exacerbated kainic acid (KA)-induced seizures. In the present study, we found that this hypersusceptibility was protracted for up to 72 h. RT-PCR profiling of hippocampal gene expression revealed rapid upregulation of 23 genes encoding cytokines, chemokines and chemokine receptors generally within 6 h after PIC challenge. The expression of most of these genes decreased by 24 h. However, two chemokine genes, i.e., Ccl19 and Cxcl13 genes, as well as two chemokine receptor genes, Ccr1 and Ccr7, remained upregulated for 72 h suggesting their possible involvement in the induction and sustenance of seizure hypersusceptibility. Also, 12 genes encoding proteins related to glutamatergic and GABAergic neurotransmission featured initial upregulation or downregulation followed by gradual normalization. The upregulation of the Gabrr3 gene remained upregulated at 72 h, congruent with its plausible role in the hypersusceptible phenotype. Moreover, the expression of ten microRNAs (miRs) was rapidly affected by PIC challenge, but their levels generally exhibited oscillating profiles over the time course of seizure hypersusceptibility. These results indicate that protracted seizure susceptibility following peripheral APR is associated with a robust polygenic response in the hippocampus. PMID:24363211

  9. Acute phase protein and antioxidant responses in dogs with experimental acute monocytic ehrlichiosis treated with rifampicin.

    PubMed

    Karnezi, Dimitra; Ceron, Jose J; Theodorou, Konstantina; Leontides, Leonidas; Siarkou, Victoria I; Martinez, Silvia; Tvarijonaviciute, Asta; Harrus, Shimon; Koutinas, Christos K; Pardali, Dimitra; Mylonakis, Mathios E

    2016-02-29

    There is currently lack of information on the changes of acute phase proteins (APP) and antioxidant markers and their clinical relevance as treatment response indicators in canine monocytic ehrlichiosis (CME). The objective of this study was to investigate the patterns of C-reactive protein (CRP), haptoglobin (Hp), ferritin and paraoxonase-1 (PON-1) during treatment of dogs with acute CME with rifampicin. Blood serum samples from ten Beagle dogs with experimental acute CME were retrospectively examined. Five dogs (Group A) were treated with rifampicin (10mg/Kg/24h), per os, for 3 weeks and 5 dogs (Group B) received no treatment (infected controls). Two Beagle dogs served as uninfected controls. Blood serum samples were serially examined prior to Ehrlichia canis inoculation and on post-inoculation days 14, 21, 28, 35 and 42. Significant changes of CRP, Hp, ferritin and PON-1 values were found in the majority of infected dogs. However, their concentrations did not differ between the two groups during the treatment observation period. The results of this study indicate that although several APP and PON-1 tend to significantly change in the majority of dogs with acute CME, they were of limited clinical relevance as treatment response indicators in this experimental setting. PMID:26854345

  10. Systematic Studies of Phase Transitions in Thermo-Responsive Polymers Used in Targeted Drug Delivery

    NASA Astrophysics Data System (ADS)

    Bradley, Janae; Denmark, Daniel; Witanachchi, Sarath

    2015-03-01

    Thermo-responsive polymers such as poly-N-isopropylacrylamide (PNIPAM) can undergo reversible phase transitions in aqueous solutions under varying temperatures. They are ideal candidates for the polymer shell of a targeted drug delivery capsule. Concentration and pH can affect the lower critical solution temperature (LCST) of the PNIPAM polymer and its physical properties. In this work, a systematic study of the factors that influence the LCST of the PNIPAM polymer mixed with Fe3O4 nanoparticles (MNPs) during thermal bath heating is presented. A series of PNIPAM solutions with varying concentrations of PNIPAM with MNPs were prepared and characterized using scanning electron microscopy. In-situ transmission measurements were used to determine the LCST of PNIPAM concentrations. A systematic decrease in the LCST was observed as the concentration of PNIPAM was increased. In addition, the impact of pH on the LCST of PNIPAM was examined by increasing the basicity of the PNIPAM solutions by adding adjusted KOH pellets. An increase in the thermal stability of the LCST was observed when the basicity of the PNIPAM solution was increased. The results from this study provide valuable information towards using these thermo-responsive polymers in targeted drug delivery. Principal Investigator

  11. HIV-specific humoral responses benefit from stronger prime in phase Ib clinical trial

    PubMed Central

    Bart, Pierre-Alexandre; Huang, Yunda; Karuna, Shelly T.; Chappuis, Samuel; Gaillard, Julien; Kochar, Nidhi; Shen, Xiaoying; Allen, Mary A.; Ding, Song; Hural, John; Liao, Hua-Xin; Haynes, Barton F.; Graham, Barney S.; Gilbert, Peter B.; McElrath, M. Juliana; Montefiori, David C.; Tomaras, Georgia D.; Pantaleo, Giuseppe; Frahm, Nicole

    2014-01-01

    BACKGROUND. Vector prime-boost immunization strategies induce strong cellular and humoral immune responses. We examined the priming dose and administration order of heterologous vectors in HIV Vaccine Trials Network 078 (HVTN 078), a randomized, double-blind phase Ib clinical trial to evaluate the safety and immunogenicity of heterologous prime-boost regimens, with a New York vaccinia HIV clade B (NYVAC-B) vaccine and a recombinant adenovirus 5–vectored (rAd5-vectored) vaccine. METHODS. NYVAC-B included HIV-1 clade B Gag-Pol-Nef and gp120, while rAd5 included HIV-1 clade B Gag-Pol and clades A, B, and C gp140. Eighty Ad5-seronegative subjects were randomized to receive 2 × NYVAC-B followed by 1 × 1010 PFU rAd5 (NYVAC/Ad5hi); 1 × 108 PFU rAd5 followed by 2 × NYVAC-B (Ad5lo/NYVAC); 1 × 109 PFU rAd5 followed by 2 × NYVAC-B (Ad5med/NYVAC); 1 × 1010 PFU rAd5 followed by 2 × NYVAC-B (Ad5hi/NYVAC); or placebo. Immune responses were assessed 2 weeks after the final vaccination. Intracellular cytokine staining measured T cells producing IFN-γ and/or IL-2; cross-clade and epitope-specific binding antibodies were determined; and neutralizing antibodies (nAbs) were assessed with 6 tier 1 viruses. RESULTS. CD4+ T cell response rates ranged from 42.9% to 93.3%. NYVAC/Ad5hi response rates (P ≤ 0.01) and magnitudes (P ≤ 0.03) were significantly lower than those of other groups. CD8+ T cell response rates ranged from 65.5% to 85.7%. NYVAC/Ad5hi magnitudes were significantly lower than those of other groups (P ≤ 0.04). IgG response rates to the group M consensus gp140 were 89.7% for NYVAC/Ad5hi and 21.4%, 84.6%, and 100% for Ad5lo/NYVAC, Ad5med/NYVAC, and Ad5hi/NYVAC, respectively, and were similar for other vaccine proteins. Overall nAb responses were low, but aggregate responses appeared stronger for Ad5med/NYVAC and Ad5hi/NYVAC than for NYVAC/Ad5hi. CONCLUSIONS. rAd5 prime followed by NYVAC boost is superior to the reverse regimen for both vaccine

  12. Effect of phase response curve skew on synchronization with and without conduction delays.

    PubMed

    Canavier, Carmen C; Wang, Shuoguo; Chandrasekaran, Lakshmi

    2013-01-01

    A central problem in cortical processing including sensory binding and attentional gating is how neurons can synchronize their responses with zero or near-zero time lag. For a spontaneously firing neuron, an input from another neuron can delay or advance the next spike by different amounts depending upon the timing of the input relative to the previous spike. This information constitutes the phase response curve (PRC). We present a simple graphical method for determining the effect of PRC shape on synchronization tendencies and illustrate it using type 1 PRCs, which consist entirely of advances (delays) in response to excitation (inhibition). We obtained the following generic solutions for type 1 PRCs, which include the pulse-coupled leaky integrate and fire model. For pairs with mutual excitation, exact synchrony can be stable for strong coupling because of the stabilizing effect of the causal limit region of the PRC in which an input triggers a spike immediately upon arrival. However, synchrony is unstable for short delays, because delayed inputs arrive during a refractory period and cannot trigger an immediate spike. Right skew destabilizes antiphase and enables modes with time lags that grow as the conduction delay is increased. Therefore, right skew favors near synchrony at short conduction delays and a gradual transition between synchrony and antiphase for pairs coupled by mutual excitation. For pairs with mutual inhibition, zero time lag synchrony is stable for conduction delays ranging from zero to a substantial fraction of the period for pairs. However, for right skew there is a preferred antiphase mode at short delays. In contrast to mutual excitation, left skew destabilizes antiphase for mutual inhibition so that synchrony dominates at short delays as well. These pairwise synchronization tendencies constrain the synchronization properties of neurons embedded in larger networks. PMID:24376399

  13. The onset of the progression of acute phase response mechanisms induced by extreme impacts can be followed by the decrease in blood levels of positive acute phase proteins.

    NASA Astrophysics Data System (ADS)

    Larina, Olga; Bekker, Anna

    Studies performed at space flights and earth-based simulation models detected the plasma indices of acute phase reaction (APR), i.e. the increase of APR cytokine mediators and alterations in the production of blood acute phase proteins (APP) at the initial stages of adaptation to altered gravity conditions. Acute phase response is the principal constituent of the functional activity of innate immunity system. Changes in plasma APPs contents are considered to serve the restoration of homeostasis state. According to trends of their concentration shifts at the evolving of acute phase reaction APPs are denoted as positive, neutral, or negative. Plasma concentrations of positive acute phase proteins α1-acid glycoprotein (α1-AGP), α1-antitrypsin (α1-AT), and neutral α2-macroglobulin (α2-M) were measured in human study at 12-hour antiorthostatic position (AOP) with 15° head down tilt and hypoxia experiments at 14% oxygen in pressure chamber. Both of these impacts were shown to produce alterations in the APP levels indicative for acute phase response. Nevertheless, in AOP experiment noticeable decrease in α1-AGP concentration occurred by hour 12, and even more pronounced decline of α1-AGP and α1-AT were found on hypoxia hours 12 and 36. Acute phase proteins α1-AGP and α2-M possess the features of proteinase inhibitors. This function is implemented by the formation of complexes with the molecules of proteolytic enzymes which subsequently are removed from the blood flow. Transient decrease in plasma concentrations of protease inhibitors on early phases of APR development was reported to result from the growth of plasma protease activity due to cathepsin release from activated leukocytes, which had not yet been compensated by enhanced APP synthesis. Being a carrier protein for positively charged and neutral substances, α1-AGP shows pronounced elevation in its blood content during APR development. As assumed, it is required for the transportation of the increased

  14. Solvent effects in the helix-coil transition model can explain the unusual biophysics of intrinsically disordered proteins

    NASA Astrophysics Data System (ADS)

    Badasyan, Artem; Mamasakhlisov, Yevgeni Sh.; Podgornik, Rudolf; Parsegian, V. Adrian

    2015-07-01

    We analyze a model statistical description of the polypeptide chain helix-coil transition, where we take into account the specificity of its primary sequence, as quantified by the phase space volume ratio of the number of all accessible states to the number corresponding to a helical conformation. The resulting transition phase diagram is then juxtaposed with the unusual behavior of the secondary structures in Intrinsically Disordered Proteins (IDPs) and a number of similarities are observed, even if the protein folding is a more complex transition than the helix-coil transition. In fact, the deficit in bulky and hydrophobic amino acids observed in IDPs, translated into larger values of phase space volume, allows us to locate the region in parameter space of the helix-coil transition that would correspond to the secondary structure transformations that are intrinsic to conformational transitions in IDPs and that is characterized by a modified phase diagram when compared to globular proteins. Here, we argue how the nature of this modified phase diagram, obtained from a model of the helix-coil transition in a solvent, would illuminate the turned-out response of IDPs to the changes in the environment conditions that follow straightforwardly from the re-entrant (cold denaturation) branch in their folding phase diagram.

  15. Analyzing responses of mouse olfactory sensory neurons using the air-phase electroolfactogram recording.

    PubMed

    Cygnar, Katherine D; Stephan, Aaron B; Zhao, Haiqing

    2010-01-01

    Animals depend on olfaction for many critical behaviors, such as finding food sources, avoiding predators, and identifying conspecifics for mating and other social interactions. The electroolfactogram (EOG) recording is an informative, easy to conduct, and reliable method to assay olfactory function at the level of the olfactory epithelium. Since the 1956 description of the EOG by Ottoson in frogs, the EOG recording has been applied in many vertebrates including salamanders, rabbits, rats, mice, and humans (reviewed by Scott and Scott-Johnson, 2002, ref. 2). The recent advances in genetic modification in mice have rekindled interest in recording the EOG for physiological characterization of olfactory function in knock-out and knock-in mice. EOG recordings have been successfully applied to demonstrate the central role of olfactory signal transduction components, and more recently to characterize the contribution of certain regulatory mechanisms to OSN responses. Odorant detection occurs at the surface of the olfactory epithelium on the cilia of OSNs, where a signal transduction cascade leads to opening of ion channels, generating a current that flows into the cilia and depolarizes the membrane. The EOG is the negative potential recorded extracellularly at the surface of the olfactory epithelium upon odorant stimulation, resulting from a summation of the potential changes caused by individual responsive OSNs in the recording field. Comparison of the amplitude and kinetics of the EOG thus provide valuable information about how genetic modification and other experimental manipulations influence the molecular signaling underlying the OSN response to odor. Here we describe an air-phase EOG recording on a preparation of mouse olfactory turbinates. Briefly, after sacrificing the mouse, the olfactory turbinates are exposed by bisecting the head along the midline and removing the septum. The turbinate preparation is then placed in the recording setup, and a recording

  16. Analyzing Responses of Mouse Olfactory Sensory Neurons Using the Air-phase Electroolfactogram Recording

    PubMed Central

    Cygnar, Katherine D.; Stephan, Aaron B.; Zhao, Haiqing

    2010-01-01

    Animals depend on olfaction for many critical behaviors, such as finding food sources, avoiding predators, and identifying conspecifics for mating and other social interactions. The electroolfactogram (EOG) recording is an informative, easy to conduct, and reliable method to assay olfactory function at the level of the olfactory epithelium. Since the 1956 description of the EOG by Ottoson in frogs1, the EOG recording has been applied in many vertebrates including salamanders, rabbits, rats, mice, and humans (reviewed by Scott and Scott-Johnson, 2002, ref. 2). The recent advances in genetic modification in mice have rekindled interest in recording the EOG for physiological characterization of olfactory function in knock-out and knock-in mice. EOG recordings have been successfully applied to demonstrate the central role of olfactory signal transduction components3-8, and more recently to characterize the contribution of certain regulatory mechanisms to OSN responses9-12. Odorant detection occurs at the surface of the olfactory epithelium on the cilia of OSNs, where a signal transduction cascade leads to opening of ion channels, generating a current that flows into the cilia and depolarizes the membrane13. The EOG is the negative potential recorded extracellularly at the surface of the olfactory epithelium upon odorant stimulation, resulting from a summation of the potential changes caused by individual responsive OSNs in the recording field2. Comparison of the amplitude and kinetics of the EOG thus provide valuable information about how genetic modification and other experimental manipulations influence the molecular signaling underlying the OSN response to odor. Here we describe an air-phase EOG recording on a preparation of mouse olfactory turbinates. Briefly, after sacrificing the mouse, the olfactory turbinates are exposed by bisecting the head along the midline and removing the septum. The turbinate preparation is then placed in the recording setup, and a

  17. Quaternion Formalism for the Intrinsic Transfer Matrix

    NASA Astrophysics Data System (ADS)

    Cretu, Nicolae; Pop, Mihail Ioan; Boer, Attila

    A quaternion formulation is applied to the intrinsic transfer matrix for longitudinal elastic wave propagation through a multilayer medium in order to find the spectral response of a sonic crystal. Resonance conditions and the band structure of the crystal are obtained. The presence of a defect is also analysed. The analysis is carried out theoretically and through simulations. A coupled oscillators model is used to validate the obtained results from a phenomenological point of view. Experimental measurements are carried out for some periodic multilayer arrangements and they are correlated with theory. The obtained spectral response and band structure are essential in characterising the sonic crystal and also in optimising its structure in order to obtain specific passbands and stopbands. The adaptedness of the quaternion formulation to periodic structures and to the inclusion of defects is considered.

  18. Photic entrainment of Period mutant mice is predicted from their phase response curves

    PubMed Central

    Pendergast, Julie S.; Friday, Rio C.; Yamazaki, Shin

    2010-01-01

    A fundamental property of circadian clocks is that they entrain to environmental cues. The circadian genes, Period1 and Period2, are involved in entrainment of the mammalian circadian system. To investigate the roles of the Period genes in photic entrainment, we constructed phase response curves (PRC) to light pulses for C57BL/6J wild-type, Per1−/−, Per2−/−, and Per3−/− mice and tested whether the PRCs accurately predict entrainment to non-24 light-dark cycles (T-cycles) and constant light (LL). The PRCs of wild-type and Per3−/− mice are similar in shape and amplitude and have relatively large delay zones and small advance zones, resulting in successful entrainment to T26, but not T21, with similar phase angles. Per1−/− mice have a high-amplitude PRC, resulting in entrainment to a broad range of T-cycles. Per2−/− mice also entrain to a wide range of T-cycles because the advance portion of their PRC is larger than wild-types. Period aftereffects following entrainment to T-cycles were similar among all genotypes. We found that the ratio of the advance portion to the delay portion of the PRC accurately predicts the lengthening of the period of the activity rhythm in LL. Wild-type, Per1−/−, and Per3−/− mice had larger delay zones than advance zones and lengthened (>24hrs) periods in LL, while Per2−/− mice had delay and advance zones that were equal in size and no period lengthening in LL. Together, these results demonstrate that PRCs are powerful tools for predicting and understanding photic entrainment of circadian mutant mice. PMID:20826680

  19. Thermo-mechanical Response and Damping Behavior of Shape Memory Alloy-MAX Phase Composites

    NASA Astrophysics Data System (ADS)

    Kothalkar, Ankush Dilip; Benitez, Rogelio; Hu, Liangfa; Radovic, Miladin; Karaman, Ibrahim

    2014-05-01

    NiTi/Ti3SiC2 interpenetrating composites that combine two unique material systems—a shape memory alloy (SMA) and a MAX phase—demonstrating two different pseudoelastic mechanisms, were processed using spark plasma sintering. The goal of mixing these two material systems was to enhance the damping behavior and thermo-mechanical response of the composite by combining two pseudoelastic mechanisms, i.e., reversible stress-induced martensitic transformation in SMA and reversible incipient kink band formation in MAX phase. Equal volume fractions of equiatomic NiTi and Ti3SiC2 were used. Microstructural characterization was conducted using scanning electron microscopy to study the distribution of NiTi, Ti3SiC2, and remnant porosity in the composite. Thermo-mechanical testing in the form of thermal cycles under constant stress levels was performed in order to characterize shape memory behavior and thereby introducing residual stresses in the composites. Evolution of two-way shape memory effect was studied and related to the presence of residual stresses in the composites. Damping behavior, implying the energy dissipation per loading-unloading cycle under increasing compressive stresses, of pure NiTi, pure Ti3SiC2, as-sintered, and thermo-mechanically cycled (TC) NiTi/Ti3SiC2 composites, was investigated and compared to the literature data. In this study, the highest energy dissipation was observed for the TC composite followed by the as-sintered (AS) composite, pure NiTi, and pure Ti3SiC2 when compared at the same applied stress levels. Both the AS and TC composites showed higher damping up to 200 MPa stress than any of the metal—MAX phase composites reported in the literature to date. The ability to enhance the performance of the composite by controlling the thermo-mechanical loading paths was further discussed.

  20. Responses of a top and a meso predator and their prey to moon phases.

    PubMed

    Penteriani, Vincenzo; Kuparinen, Anna; del Mar Delgado, Maria; Palomares, Francisco; López-Bao, José Vicente; Fedriani, José María; Calzada, Javier; Moreno, Sacramento; Villafuerte, Rafael; Campioni, Letizia; Lourenço, Rui

    2013-11-01

    We compared movement patterns and rhythms of activity of a top predator, the Iberian lynx Lynx pardinus, a mesopredator, the red fox Vulpes vulpes, and their shared principal prey, the rabbit Oryctolagus cuniculus, in relation to moon phases. Because the three species are mostly nocturnal and crepuscular, we hypothesized that the shared prey would reduce its activity at most risky moon phases (i.e. during the brightest nights), but that fox, an intraguild prey of lynx, would avoid lynx activity peaks at the same time. Rabbits generally moved further from their core areas on darkest nights (i.e. new moon), using direct movements which minimize predation risk. Though rabbits responded to the increased predation risk by reducing their activity during the full moon, this response may require several days, and the moon effect we observed on the rabbits had, therefore, a temporal gap. Lynx activity patterns may be at least partially mirroring rabbit activity: around new moons, when rabbits moved furthest and were more active, lynxes reduced their travelling distances and their movements were concentrated in the core areas of their home ranges, which generally correspond to areas of high density of rabbits. Red foxes were more active during the darkest nights, when both the conditions for rabbit hunting were the best and lynxes moved less. On the one hand, foxes increased their activity when rabbits were further from their core areas and moved with more discrete displacements; on the other hand, fox activity in relation to the moon seemed to reduce dangerous encounters with its intraguild predator. PMID:23579570

  1. Intrinsic Josephson Junctions with Intermediate Damping

    NASA Astrophysics Data System (ADS)

    Warburton, Paul A.; Saleem, Sajid; Fenton, Jon C.; Speller, Susie; Grovenor, Chris R. M.

    2011-03-01

    In cuprate superconductors, adjacent cuprate double-planes are intrinsically Josephson-coupled. For bias currents perpendicular to the planes, the current-voltage characteristics correspond to those of an array of underdamped Josephson junctions. We will discuss our experiments on sub-micron Tl-2212 intrinsic Josephson junctions (IJJs). The dynamics of the IJJs at the plasma frequency are moderately damped (Q ~ 8). This results in a number of counter-intuitive observations, including both a suppression of the effect of thermal fluctuations and a shift of the skewness of the switching current distributions from negative to positive as the temperature is increased. Simulations confirm that these phenomena result from repeated phase slips as the IJJ switches from the zero-voltage to the running state. We further show that increased dissipation counter-intuitively increases the maximum supercurrent in the intermediate damping regime (PRL vol. 103, art. no. 217002). We discuss the role of environmental dissipation on the dynamics and describe experiments with on-chip lumped-element passive components in order control the environment seen by the IJJs. Work supported by EPSRC.

  2. Impact of Baseline BCR-ABL Mutations on Response to Nilotinib in Patients With Chronic Myeloid Leukemia in Chronic Phase

    PubMed Central

    Hughes, Timothy; Saglio, Giuseppe; Branford, Susan; Soverini, Simona; Kim, Dong-Wook; Müller, Martin C.; Martinelli, Giovanni; Cortes, Jorge; Beppu, Lan; Gottardi, Enrico; Kim, Dongho; Erben, Philipp; Shou, Yaping; Haque, Ariful; Gallagher, Neil; Radich, Jerald; Hochhaus, Andreas

    2009-01-01

    Purpose Nilotinib is a second-generation tyrosine kinase inhibitor indicated for the treatment of patients with chronic myeloid leukemia (CML) in chronic phase (CP; CML-CP) and accelerated phase (AP; CML-AP) who are resistant to or intolerant of prior imatinib therapy. In this subanalysis of a phase II study of nilotinib in patients with imatinib-resistant or imatinib-intolerant CML-CP, the occurrence and impact of baseline and newly detectable BCR-ABL mutations were assessed. Patients and Methods Baseline mutation data were assessed in 281 (88%) of 321 patients with CML-CP in the phase II nilotinib registration trial. Results Among imatinib-resistant patients, the frequency of mutations at baseline was 55%. After 12 months of therapy, major cytogenetic response (MCyR) was achieved in 60%, complete cytogenetic response (CCyR) in 40%, and major molecular response (MMR) in 29% of patients without baseline mutations versus 49% (P = .145), 32% (P = .285), and 22% (P = .366), respectively, of patients with mutations. Responses in patients who harbored mutations with high in vitro sensitivity to nilotinib (50% inhibitory concentration [IC50] ≤ 150 nM) or mutations with unknown nilotinib sensitivity were equivalent to those responses for patients without mutations (not significant). Patients with mutations that were less sensitive to nilotinib in vitro (IC50 > 150 nM; Y253H, E255V/K, F359V/C) had less favorable responses, as 13%, 43%, and 9% of patients with each of these mutations, respectively, achieved MCyR; none achieved CCyR. Conclusion For most patients with imatinib resistance and with mutations, nilotinib offers a substantial probability of response. However, mutational status at baseline may influence response. Less sensitive mutations that occurred at three residues defined in this study, as well as the T315I mutation, may be associated with less favorable responses to nilotinib. PMID:19652056

  3. Characterization of submillisecond response optical addressing phase modulator based on low light scattering polymer network liquid crystal

    NASA Astrophysics Data System (ADS)

    Xiangjie, Zhao; Cangli, Liu; Jiazhu, Duan; Dayong, Zhang; Yongquan, Luo

    2015-01-01

    Optically addressed conventional nematic liquid crystal spatial light modulator has attracted wide research interests. But the slow response speed limited its further application. In this paper, polymer network liquid crystal (PNLC) was proposed to replace the conventional nematic liquid crystal to enhance the response time to the order of submillisecond. The maximum light scattering of the employed PNLC was suppressed to be less than 2% at 1.064 μm by optimizing polymerization conditions and selecting large viscosity liquid crystal as solvent. The occurrence of phase ripple phenomenon due to electron diffusion and drift in photoconductor was found to deteriorate the phase modulation effect of the optical addressed PNLC phase modulator. The wavelength effect and AC voltage frequency effect on the on state dynamic response of phase change was investigated by experimental methods. These effects were interpreted by electron diffusion and drift theory based on the assumption that free electron was inhomogeneously distributed in accordance with the writing beam intensity distribution along the incident direction. The experimental results indicated that the phase ripple could be suppressed by optimizing the wavelength of the writing beam and the driving AC voltage frequency when varying the writing beam intensity to generate phase change in 2π range. The modulation transfer function was also measured.

  4. Characterization of submillisecond response optical addressing phase modulator based on low light scattering polymer network liquid crystal

    SciTech Connect

    Xiangjie, Zhao E-mail: zxjdouble@gmail.com; Cangli, Liu; Jiazhu, Duan; Dayong, Zhang; Yongquan, Luo

    2015-01-07

    Optically addressed conventional nematic liquid crystal spatial light modulator has attracted wide research interests. But the slow response speed limited its further application. In this paper, polymer network liquid crystal (PNLC) was proposed to replace the conventional nematic liquid crystal to enhance the response time to the order of submillisecond. The maximum light scattering of the employed PNLC was suppressed to be less than 2% at 1.064 μm by optimizing polymerization conditions and selecting large viscosity liquid crystal as solvent. The occurrence of phase ripple phenomenon due to electron diffusion and drift in photoconductor was found to deteriorate the phase modulation effect of the optical addressed PNLC phase modulator. The wavelength effect and AC voltage frequency effect on the on state dynamic response of phase change was investigated by experimental methods. These effects were interpreted by electron diffusion and drift theory based on the assumption that free electron was inhomogeneously distributed in accordance with the writing beam intensity distribution along the incident direction. The experimental results indicated that the phase ripple could be suppressed by optimizing the wavelength of the writing beam and the driving AC voltage frequency when varying the writing beam intensity to generate phase change in 2π range. The modulation transfer function was also measured.

  5. Linear response and Berry curvature in two-dimensional topological phases

    NASA Astrophysics Data System (ADS)

    Bradlyn, Barry J.

    cannot contribute to low-temperature thermoelectric transport other than the ordinary Hall conductivity; the other thermoelectric effects (if they occur) are thus purely edge effects. The stress response to time-dependent strains is given by the Hall viscosity, which is robust against perturbations and related to the spin current. Finally, we address the issue of calculating the topological central charge from bulk wavefunctions for a topological phase. Using the form of the topological terms in the induced action, we show that we can calculate the various coefficients of these terms as Berry curvatures associated to certain metric and electromagnetic vector potential perturbations. We carry out this computation explicitly for quantum Hall trial wavefunctions that can be represented as conformal blocks in a chiral conformal field theory (CFT). These calculations make use of the gauge and gravitational anomalies in the underlying chiral CFT.

  6. Quasar redshifts: the intrinsic component

    NASA Astrophysics Data System (ADS)

    Hansen, Peter M.

    2016-09-01

    The large observed redshift of quasars has suggested large cosmological distances and a corresponding enormous energy output to explain the brightness or luminosity as seen at earth. Alternative or complementary sources of redshift have not been identified by the astronomical community. This study examines one possible source of additional redshift: an intrinsic component based on the plasma characteristics of high temperature and high electron density which are believed to be present.

  7. Decoherence: Intrinsic, Extrinsic, and Environmental

    NASA Astrophysics Data System (ADS)

    Stamp, Philip

    2012-02-01

    Environmental decoherence times have been difficult to predict in solid-state systems. In spin systems, environmental decoherence is predicted to arise from nuclear spins, spin-phonon interactions, and long-range dipolar interactions [1]. Recent experiments have confirmed these predictions quantitatively in crystals of Fe8 molecules [2]. Coherent spin dynamics was observed over macroscopic volumes, with a decoherence Q-factor Qφ= 1.5 x10^6 (the upper predicted limit in this system being Qφ= 6 x10^7). Decoherence from dipolar interactions is particularly complex, and depends on the shape and the quantum state of the system. No extrinsic ``noise'' decoherence was observed. The generalization to quantum dot and superconducting qubit systems is also discussed. We then discuss searches for ``intrinsic'' decoherence [3,4], coming from non-linear corrections to quantum mechanics. Particular attention is paid to condensed matter tests of such intrinsic decoherence, in hybrid spin/optomechanical systems, and to ways of distinguishing intrinsic decoherence from environmental and extrinsic decoherence sources. [4pt] [1] Morello, A. Stamp, P. C. E. & Tupitsyn, Phys. Rev. Lett. 97, 207206 (2006).[0pt] [2] S. Takahashi et al., Nature 476, 76 (2011).[0pt] [3] Stamp, P. C. E., Stud. Hist. Phil. Mod. Phys. 37, 467 (2006). [0pt] [4] Stamp, P.C.E., Phil. Trans. Roy. Soc. A (to be published)

  8. Troponins, intrinsic disorder, and cardiomyopathy.

    PubMed

    Na, Insung; Kong, Min J; Straight, Shelby; Pinto, Jose R; Uversky, Vladimir N

    2016-08-01

    Cardiac troponin is a dynamic complex of troponin C, troponin I, and troponin T (TnC, TnI, and TnT, respectively) found in the myocyte thin filament where it plays an essential role in cardiac muscle contraction. Mutations in troponin subunits are found in inherited cardiomyopathies, such as hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). The highly dynamic nature of human cardiac troponin and presence of numerous flexible linkers in its subunits suggest that understanding of structural and functional properties of this important complex can benefit from the consideration of the protein intrinsic disorder phenomenon. We show here that mutations causing decrease in the disorder score in TnI and TnT are significantly more abundant in HCM and DCM than mutations leading to the increase in the disorder score. Identification and annotation of intrinsically disordered regions in each of the troponin subunits conducted in this study can help in better understanding of the roles of intrinsic disorder in regulation of interactomes and posttranslational modifications of these proteins. These observations suggest that disease-causing mutations leading to a decrease in the local flexibility of troponins can trigger a whole plethora of functional changes in the heart. PMID:27074551

  9. Visual representations are dominated by intrinsic fluctuations correlated between areas.

    PubMed

    Henriksson, Linda; Khaligh-Razavi, Seyed-Mahdi; Kay, Kendrick; Kriegeskorte, Nikolaus

    2015-07-01

    Intrinsic cortical dynamics are thought to underlie trial-to-trial variability of visually evoked responses in animal models. Understanding their function in the context of sensory processing and representation is a major current challenge. Here we report that intrinsic cortical dynamics strongly affect the representational geometry of a brain region, as reflected in response-pattern dissimilarities, and exaggerate the similarity of representations between brain regions. We characterized the representations in several human visual areas by representational dissimilarity matrices (RDMs) constructed from fMRI response-patterns for natural image stimuli. The RDMs of different visual areas were highly similar when the response-patterns were estimated on the basis of the same trials (sharing intrinsic cortical dynamics), and quite distinct when patterns were estimated on the basis of separate trials (sharing only the stimulus-driven component). We show that the greater similarity of the representational geometries can be explained by coherent fluctuations of regional-mean activation within visual cortex, reflecting intrinsic dynamics. Using separate trials to study stimulus-driven representations revealed clearer distinctions between the representational geometries: a Gabor wavelet pyramid model explained representational geometry in visual areas V1-3 and a categorical animate-inanimate model in the object-responsive lateral occipital cortex. PMID:25896934

  10. Visual representations are dominated by intrinsic fluctuations correlated between areas

    PubMed Central

    Henriksson, Linda; Khaligh-Razavi, Seyed-Mahdi; Kay, Kendrick; Kriegeskorte, Nikolaus

    2015-01-01

    Intrinsic cortical dynamics are thought to underlie trial-to-trial variability of visually evoked responses in animal models. Understanding their function in the context of sensory processing and representation is a major current challenge. Here we report that intrinsic cortical dynamics strongly affect the representational geometry of a brain region, as reflected in response-pattern dissimilarities, and exaggerate the similarity of representations between brain regions. We characterized the representations in several human visual areas by representational dissimilarity matrices (RDMs) constructed from fMRI response-patterns for natural image stimuli. The RDMs of different visual areas were highly similar when the response-patterns were estimated on the basis of the same trials (sharing intrinsic cortical dynamics), and quite distinct when patterns were estimated on the basis of separate trials (sharing only the stimulus-driven component). We show that the greater similarity of the representational geometries can be explained by coherent fluctuations of regional-mean activation within visual cortex, reflecting intrinsic dynamics. Using separate trials to study stimulus-driven representations revealed clearer distinctions between the representational geometries: a Gabor wavelet pyramid model explained representational geometry in visual areas V1–3 and a categorical animate–inanimate model in the object-responsive lateral occipital cortex. PMID:25896934

  11. Radiation-induced p53 protein response in the A549 cell line is culture growth-phase dependent

    SciTech Connect

    Johnson, N.F.; Gurule, D.M.; Carpenter, T.R.

    1995-12-01

    One role of the p53 tumor suppressor protein has been recently revealed. Kastan, M.B. reported that p53 protein accumulates in cells exposed to ionizing radiation. The accumulation of p53 protein is in response to DNA damage, most importantly double-strand breaks, that results from exposure to ionizing radiation. The rise in cellular p53 levels is necessary for an arrest in the G{sub 1} phase of the cell cycle to provide additional time for DNA repair. The p53 response has also been demonstrated to enhance PCNA-dependent repair. p53 is thus an important regulator of the cellular response to DNA-damaging radiation. From this data, it can be concluded that the magnitude of the p53 response is not dependent on the phase of culture growth.

  12. Intrinsic Coupling Modes in Source-Reconstructed Electroencephalography

    PubMed Central

    Breakspear, Michael; Britz, Juliane; Boonstra, Tjeerd W.

    2014-01-01

    Abstract Intrinsic coupling of neuronal assemblies constitutes a key feature of ongoing brain activity, yielding the rich spatiotemporal patterns observed in neuroimaging data and putatively supporting cognitive processes. Intrinsic coupling has been investigated in electrophysiological recordings using two types of functional connectivity measures: amplitude and phase coupling. These two coupling modes differ in their likely causes and functions, and have been proposed to provide complementary insights into intrinsic neuronal interactions. Here, we investigate the relationship between amplitude and phase coupling in source-reconstructed electroencephalography (EEG). Volume conduction is a key obstacle for connectivity analysis in EEG—we therefore also test the envelope correlation of orthogonalized signals and the phase lag index. Functional connectivity between six seed source regions (bilateral visual, sensorimotor, and auditory cortices) and all other cortical voxels was computed. For all four measures, coupling between homologous sensory areas in both hemispheres was significantly higher than with other voxels at the same physical distance. The frequency of significant coupling differed between sensory areas: 10 Hz for visual, 30 Hz for auditory, and 40 Hz for sensorimotor cortices. By contrasting envelope correlations and phase locking values, we observed two distinct clusters of voxels showing a different relationship between amplitude and phase coupling. Large clusters contiguous to the seed regions showed an identity (1:1) relationship between amplitude and phase coupling, whereas a cluster located around the contralateral homologous regions showed higher phase than amplitude coupling. These results show a relationship between intrinsic coupling modes that is distinct from the effect of volume conduction. PMID:25230358

  13. Fanconi anemia proteins FANCD2 and FANCI exhibit different DNA damage responses during S-phase

    PubMed Central

    Sareen, Archana; Chaudhury, Indrajit; Adams, Nicole; Sobeck, Alexandra

    2012-01-01

    Fanconi anemia (FA) pathway members, FANCD2 and FANCI, contribute to the repair of replication-stalling DNA lesions. FA pathway activation relies on phosphorylation of FANCI by the ataxia telangiectasia and Rad3-related (ATR) kinase, followed by monoubiquitination of FANCD2 and FANCI by the FA core complex. FANCD2 and FANCI are thought to form a functional heterodimer during DNA repair, but it is unclear how dimer formation is regulated or what the functions of the FANCD2–FANCI complex versus the monomeric proteins are. We show that the FANCD2–FANCI complex forms independently of ATR and FA core complex, and represents the inactive form of both proteins. DNA damage-induced FA pathway activation triggers dissociation of FANCD2 from FANCI. Dissociation coincides with FANCD2 monoubiquitination, which significantly precedes monoubiquitination of FANCI; moreover, monoubiquitination responses of FANCD2 and FANCI exhibit distinct DNA substrate specificities. A phosphodead FANCI mutant fails to dissociate from FANCD2, whereas phosphomimetic FANCI cannot interact with FANCD2, indicating that FANCI phosphorylation is the molecular trigger for FANCD2–FANCI dissociation. Following dissociation, FANCD2 binds replicating chromatin prior to—and independently of—FANCI. Moreover, the concentration of chromatin-bound FANCD2 exceeds that of FANCI throughout replication. Our results suggest that FANCD2 and FANCI function separately at consecutive steps during DNA repair in S-phase. PMID:22753026

  14. EXPERIMENTAL INFECTION WITH Toxocara cati IN PIGS: MIGRATORY PATTERN AND PATHOLOGICAL RESPONSE IN EARLY PHASE

    PubMed Central

    Sommerfelt, Irma Estela; Duchene, Adriana; Daprato, Betina; Lopez, Clara María; Cardillo, Natalia; Franco, Aníbal Juan

    2014-01-01

    Experimental inoculations of approximately 100,000 infective Toxocara cati larval eggs were done in twelve pigs. The T. cati eggs used for inoculation were collected from cat's feces. Another group of three pigs served as an uninfected control. Groups of infected pigs were euthanized at seven, 14, 21, and 28 days post-inoculation (dpi). Tissue samples were taken for digestion and histopathology changes in early phase. The number of larvae recovered from the lungs peaked at seven and 14 dpi and were also present at 21, and 28 dpi. Larvae of T. cati were present in the lymph nodes of the small and large intestine at seven, 14, and 28 dpi and at seven, 14, 21, and 28 dpi respectively. In other studied tissues, no larvae or less than one larva per gram was detected. The pathological response observed in the liver and lungs at seven and 14 dpi, showed white spots on the liver surface and areas of consolidation were observed in the lungs. The lungs showed an inflammatory reaction with larvae in center at 28 dpi. In the liver we observed periportal and perilobular hepatitis. The lymph nodes of the intestines displayed eosinophil lymphadenitis with reactive centers containing parasitic forms in some of them. The granulomatous reaction was not observed in any tissues. The role of the other examined tissues had less significance. The relevance of this parasite as an etiological agent that leads to disease in paratenic hosts is evident. PMID:25076437

  15. A new, vapour-phase mechanism for stomatal responses to humidity and temperature.

    PubMed

    Peak, David; Mott, Keith A

    2011-01-01

    A new mechanism for stomatal responses to humidity and temperature is proposed. Unlike previously-proposed mechanisms, which rely on liquid water transport to create water potential gradients within the leaf, the new mechanism assumes that water transport to the guard cells is primarily through the vapour phase. Under steady-state conditions, guard cells are assumed to be in near-equilibrium with the water vapour in the air near the bottom of the stomatal pore. As the water potential of this air varies with changing air humidity and leaf temperature, the resultant changes in guard cell water potential produce stomatal movements. A simple, closed-form, mathematical model based on this idea is derived. The new model is parameterized for a previously published set of data and is shown to fit the data as well as or better than existing models. The model contains mathematical elements that are consistent with previously-proposed mechanistic models based on liquid flow as well as empirical models based on relative humidity. As such, it provides a mechanistic explanation for the realm of validity for each of these approaches. PMID:20880202

  16. Localization of intrinsic factor and complement fixing intrinsic factor–intrinsic factor antibody complex in parietal cell of man

    PubMed Central

    Jacob, Elizabeth; Glass, G. B. J.

    1971-01-01

    In an attempt to localize intrinsic factor in the human parietal cell, and to study its intracellular union with the intrinsic factor antibody and complement, intrinsic factor antibody was separated from coexisting parietal cell antibody in pernicious anaemia sera by gel filtration. Intrinsic factor antibody of both `binding' and `blocking' type was also produced in rabbits by immunization with semi-purified human intrinsic factor–[57Co]B12 complex. Intrinsic factor antibody obtained from both sources produced fluorescence in the human parietal cells in the indirect Coons' test in the presence of fluoresceinated anti-human IgG. The fluorescence was localized peripherally, at the cell membrane. When instead of the fluoresceinated anti-human IgG a fluoresceinated anti-human complement (C) serum and normal complement containing serum were used, intrinsic factor antibody from both sources produced fluorescence of the entire parietal cell cytoplasm of the human mucosa. Thus, intrinsic factor was localized at highest concentration at the membrane of the parietal cell in man, the intrinsic factor antibody–intrinsic factor complex was demonstrated within the human parietal cell, and evidence was obtained that this antigen–antibody complex fixes complement (C). The possible role of the intrinsic factor–intrinsic factor antibody–complement complex in the development of gastric atrophy in pernicious anaemia has been considered. ImagesFIG. 3FIG. 4FIG. 5 PMID:4995933

  17. Intrinsic modulation of pulse-coupled integrate-and-fire neurons

    NASA Astrophysics Data System (ADS)

    Coombes, S.; Lord, G. J.

    1997-11-01

    Intrinsic neuromodulation is observed in sensory and neuromuscular circuits and in biological central pattern generators. We model a simple neuronal circuit with a system of two pulse-coupled integrate-and-fire neurons and explore the parameter regimes for periodic firing behavior. The inclusion of biologically realistic features shows that the speed and onset of neuronal response plays a crucial role in determining the firing phase for periodic rhythms. We explore the neurophysiological function of distributed delays arising from both the synaptic transmission process and dendritic structure as well as discrete delays associated with axonal communication delays. Bifurcation and stability diagrams are constructed with a mixture of simple analysis, numerical continuation and the Kuramoto phase-reduction technique. Moreover, we show that, for asynchronous behavior, the strength of electrical synapses can control the firing rate of the system.

  18. Influence of Menstrual Cycle Phase on Neural and Craving Responses to Appetitive Smoking Cues in Naturally Cycling Females

    PubMed Central

    Jagannathan, Kanchana; Wetherill, Reagan R.; Johnson, Barbara; Kelly, Shannon; Langguth, Jamison; Mumma, Joel; Childress, Anna Rose

    2015-01-01

    Introdu ction: Functional magnetic resonance imaging (fMRI) has been used extensively in an attempt to understand brain vulnerabilities that mediate maladaptive responses to drug cues. Using perfusion fMRI, we have consistently shown reward-related activation (medial orbitofrontal cortex/ventral striatum) to smoking cues (SCs). Because preclinical and clinical studies generally show that progesterone may reduce reward and craving, we hypothesized that females in the follicular phase of the cycle (FPs; when progesterone levels are low) would have greater reward-related neural responses to SCs compared with females in the luteal phase (LPs). Methods: Sated cigarette-dependent premenopausal naturally cycling females underwent pseudo-continuous arterial spin-labeled perfusion fMRI during exposure to 10-min audio visual clips of appetitive SCs and non-SCs. Brain responses to SCs relative to non-SCs were examined among females grouped according to menstrual cycle (MC) phase at the time of scanning (22 FPs, 15 LPs). Craving scores were acquired pre- and post-SC exposure. Results: FPs showed increased neural responses to SCs compared with non-SCs in the medial orbitofrontal cortex (p ≤ .05corrected), whereas LPs did not. FPs reported SC-elicited craving (p ≤ .005), whereas LPs did not. Within FPs, SC-induced craving correlated with increased neural responses in the anterior insula (r = 0.73, p < .0001). Conclusions: FPs may be more vulnerable to relapse during appetitive SC exposure than LPs. Because the influence of MC phase on drug cue neural activity has not been examined, these results contribute to our knowledge of the neurobiological underpinnings of responses to drug cues, and they highlight the importance of monitoring menstrual cycle phase in all areas of addiction research. PMID:25762748

  19. Intrinsic radiation resistance in human chondrosarcoma cells

    SciTech Connect

    Moussavi-Harami, Farid; Mollano, Anthony; Martin, James A.; Ayoob, Andrew; Domann, Frederick E.; Gitelis, Steven; Buckwalter, Joseph A. . E-mail: joseph-buckwalter@uiowa.edu

    2006-07-28

    Human chondrosarcomas rarely respond to radiation treatment, limiting the options for eradication of these tumors. The basis of radiation resistance in chondrosarcomas remains obscure. In normal cells radiation induces DNA damage that leads to growth arrest or death. However, cells that lack cell cycle control mechanisms needed for these responses show intrinsic radiation resistance. In previous work, we identified immortalized human chondrosarcoma cell lines that lacked p16{sup ink4a}, one of the major tumor suppressor proteins that regulate the cell cycle. We hypothesized that the absence of p16{sup ink4a} contributes to the intrinsic radiation resistance of chondrosarcomas and that restoring p16{sup ink4a} expression would increase their radiation sensitivity. To test this we determined the effects of ectopic p16{sup ink4a} expression on chondrosarcoma cell resistance to low-dose {gamma}-irradiation (1-5 Gy). p16{sup ink4a} expression significantly increased radiation sensitivity in clonogenic assays. Apoptosis did not increase significantly with radiation and was unaffected by p16{sup ink4a} transduction of chondrosarcoma cells, indicating that mitotic catastrophe, rather than programmed cell death, was the predominant radiation effect. These results support the hypothesis that p16{sup ink4a} plays a role in the radiation resistance of chondrosarcoma cell lines and suggests that restoring p16 expression will improve the radiation sensitivity of human chondrosarcomas.

  20. Intrinsic spin torque without spin-orbit coupling

    PubMed Central

    Kim, Kyoung-Whan; Lee, Kyung-Jin; Lee, Hyun-Woo; Stiles, M. D.

    2016-01-01

    We derive an intrinsic contribution to the non-adiabatic spin torque for non-uniform magnetic textures. It differs from previously considered contributions in several ways and can be the dominant contribution in some models. It does not depend on the change in occupation of the electron states due to the current flow but rather is due to the perturbation of the electronic states when an electric field is applied. Therefore it should be viewed as electric-field-induced rather than current-induced. Unlike previously reported non-adiabatic spin torques, it does not originate from extrinsic relaxation mechanisms nor spin-orbit coupling. This intrinsic non-adiabatic spin torque is related by a chiral connection to the intrinsic spin-orbit torque that has been calculated from the Berry phase for Rashba systems. PMID:26877628

  1. Finite Element Modeling of the Magnetotelluric Phase Tensor Response to Evaluate Sensitivity to Lateral and Vertical Resistivity Contrasts

    NASA Astrophysics Data System (ADS)

    Hawkes, S.; McClain, J. S.

    2015-12-01

    Phase tensor analysis of magnetotelluric data is a relatively new technique introduced by Caldwell et. al. (2004) and requires substantial research efforts to evaluate the capabilities of the method. We have conducted finite element (FE) modeling using the AC/DC module of Comsol Multiphysics to determine the effect of resistivity structure on the phase tensor response. Measurements are made at eleven frequencies from 10-104 Hz at points on a 5x5 grid above various simple model geometries. Phase tensor plotting methods are adapted from Booker (2013) and involve displaying data graphically as stacks of colored ellipses. This allows for interpretation across the frequency spectrum vertically as well as laterally between stations. Two types of plot are presented for each model, a "ϕmin plot" where the ellipses are colored according to the minimum principle phase and a "delta plot" where the ellipses are colored according to the difference between the principle phases (ϕmax - ϕmin), which provides a quantification of the phase anisotropy. Results suggest that the principle phases ϕmin and ϕmax are sensitive to vertical resistivity contrasts but not lateral resistivity contrasts. Conversely, delta plots reveal sensitivity to lateral resistivity contrasts but not vertical resistivity contrasts. A clear distance relationship is observed with proximity to the boundary controlling the frequency range that senses a lateral resistivity contrast. Rotation of the phase tensor ellipses and increased skew values occur in the presence of resistivity contrasts that strike nonparallel to the source field, with the effect increasing towards lower frequencies. The total phase tensor response is confirmed to be sensitive to both vertical and lateral resistivity contrasts and can be used effectively to interpret subsurface resistivity structure.

  2. Intrinsic dephasing in one-dimensional ultracold atom interferometers.

    PubMed

    Bistritzer, R; Altman, E

    2007-06-12

    Quantum-phase fluctuations prevent true long-range phase order from forming in interacting 1D condensates, even at zero temperature. Nevertheless, by dynamically splitting the condensate into two parallel decoupled tubes the system can be prepared with a macroscopic relative phase, facilitating interferometric measurement. Here, we describe a dephasing mechanism whereby the quantum-phase fluctuations, which are so effective in equilibrium, act to destroy the macroscopic relative phase that was imposed as a nonequilibrium initial condition. We show that the phase coherence between the condensates decays exponentially with a dephasing time that depends on intrinsic parameters: the interaction strength, sound velocity, and density. Interestingly, significant temperature dependence appears only above a cross-over scale T*. In contrast to the usual phase diffusion, which is essentially an effect of confinement and leads to Gaussian decay, the exponential dephasing caused by fluctuations is a bulk effect that survives the thermodynamic limit. PMID:17548834

  3. Western Wind and Solar Integration Study Phase 3 -- Frequency Response and Transient Stability (Report and Executive Summary)

    SciTech Connect

    Miller, N. W.; Shao, M.; Pajic, S.; D'Aquila, R.

    2014-12-01

    The primary objectives of Phase 3 of the Western Wind and Solar Integration Study (WWSIS-3) were to examine the large-scale transient stability and frequency response of the Western Interconnection with high wind and solar penetration, and to identify means to mitigate any adverse performance impacts via transmission reinforcements, storage, advanced control capabilities, or other alternatives.

  4. Prenatal transportation alters the acute phase response (APR) of bull calves exposed to a lipopolysaccharide (LPS) challenge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was designed to determine if prenatal transportation influences the acute phase response (APR) to a postnatal Lipopolysaccharide (LPS) challenge. Pregnant Brahman cows (n=96) matched by age and parity were separated into transported (TRANS; n=48; transported for 2 hours on gestational day...

  5. The effect of feeding endophyte-infected fescue on the acute phase response to lipopolysaccharide in beef heifers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Angus heifers (n = 22; 292 ± 9.0 kg body weight) were paired by body weight and randomly placed on either an endophyte-infected (E+) or endophyte-free (E-) diet for 10 days to determine the influence of feeding endophyte-infected fescue on the physiological and acute phase responses of beef heifers ...

  6. Supplementation of Lactobacillus acidophilus fermentation product can attenuate the acute phase response following a lipopolysaccharide challenge in pigs.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was designed to determine if feeding a Lactobacillus acidophilus fermentation product to weaned pigs would reduce stress and acute phase responses (APR) following a lipopolysaccharide (LPS) challenge. Pigs (n=30; 6.4±0.1 kilograms body weight) were housed individually in pens with ad libi...

  7. MICROBIAL RESPONSES TO IN SITU CHEMICAL OXIDATION, SIX-PHASE HEATING, AND STEAM INJECTION REMEDIATION TECHNOLOGIES IN GROUND WATER

    EPA Science Inventory

    The evaluation of microbial responses to three in situ source removal remedial technologies including permanganate-based in-situ chemical oxidation (ISCO), six-phase heating (SPH), and steam injection (SI) was performed at Cape Canaveral Air Station in Florida. The investigatio...

  8. Does the human odometer use an extrinsic or intrinsic metric?

    PubMed

    Chrastil, Elizabeth R; Warren, William H

    2014-01-01

    It is commonly assumed that path integration is based on an extrinsic measure of the objective distance traversed during locomotion. In contrast, biological odometers may rely on embodied intrinsic measures, such as idiothetic information specific to an action mode. We investigated this question using a distance reproduction task in which participants traveled an outbound distance and then reproduced that distance using the same or a different action mode. The extrinsic model predicted that distance reproduction should be invariant across action modes, whereas the intrinsic model predicted invariance only within an action mode. In Experiment 1, we held the outbound mode constant while varying the response mode (walk-walk, walk-throw) and corrected for response production error (view-walk, view-throw). In Experiment 2, we crossed different gaits in the outbound and response modes (walk, gallop). In both cases, we found that distance reproduction was significantly more accurate when the outbound and response modes matched, consistent with the intrinsic model. The results indicate that the human odometer preferentially relies on an intrinsic, rather than an extrinsic, metric. This solution is sufficient to support successful path integration within an action mode (but not across action modes), without the difficulties of objective distance estimation. PMID:24197502

  9. Maximizing the number of coexisting phases near invariant critical points for giant electrocaloric and electromechanical responses in ferroelectrics

    NASA Astrophysics Data System (ADS)

    Liu, Z. K.; Li, Xinyu; Zhang, Q. M.

    2012-08-01

    Ferroelectric materials directly convert electrical energy to mechanical or thermal work and are critical to applications such as sensors, transducers, actuators, and cooling devices. Numerous efforts have been undertaken to develop materials with high electrocaloric (EC) and electromechanical (EM) responses. Here, we present a theoretical analysis, based on thermodynamic fundamentals, for developing ferroelectric materials with high EC and EM responses, i.e., searching for and operating the material near an invariant critical point (ICP). We show that by tailoring the constraints to maximize the number of coexisting phases near ICPs, large EC and EM responses may be realized.

  10. Looking the World from Inside:. Intrinsic Geometry of Complex Systems

    NASA Astrophysics Data System (ADS)

    Boi, L.

    2012-12-01

    In this paper we shall address some meeting points between geometry and biology, in order to show that geometrical things and transformations take part intrinsically in the living systems. We focus on some features of macromolecular structures like DNA-proteins complexes. All things we speak about take place in the 3-dimensional space of a living cell and particularly in its nucleus, which of course interacts in many ways and at different levels with the whole cell, its cytoplasm and the organelles. Ideally, we think we should rather consider, instead of a 3-dimensional space, a configuration space characterized by all its phase spaces, since a living being is a very complex dynamical system, but this would be a too difficult, impossible task. This is of course a very partial view, an oversimplification, of what really happen in our organisms. Nevertheless, We believe that in biology we are today facing the following problem: how small or local changes in a living system do affect the global behaviour and response of the whole organisms? We search for an answer by arguing that mostly overall features of living systems are emergent properties of organization and regulation defined at the macroscopic level of their morphology and physiological behaviours, and also by showing that in complex living systems self-organization ensures robustness without loss of plasticity, in the sense that perturbations in the interactions properties of its single parts generally do not have damaging consequences on the living form as a whole.

  11. Intrinsic bioremediation modeling to support Superfund site closure

    SciTech Connect

    Bedard, A.H.; Day, M.J.; Johnson, R.H.; Ritter, K.J.; Stancel, S.G.; Thomson, J.A.M.

    1997-09-01

    Closure of the groundwater component of a major Superfund site has been accomplished by a combination of source control, engineered in-situ bioremediation, and subsequent long-term intrinsic bioremediation. Engineered bioremediation outside the source control area resulted in very significant contaminant mass removal. This allowed intrinsic bioremediation to be considered as a passive remedial management method of achieving cleanup objectives after active remediation needed. Modeling demonstrated that intrinsic bioremediation would achieve cleanup objectives (for this site, Federal drinking water standards) within ten years of shutdown of the active bioremediation system. Modeling showed that residual electron acceptors and nutrients distributed in the aquifer during engineered bioremediation greatly enhance the intrinsic bioremediation process. The results of the modeling effort led to the active system being shut down a year ahead of schedule, allowing the project to move into a low-maintenance intrinsic bioremediation and long-term monitoring phase. The modeling demonstration coupled Visual MODFLOW{copyright} and BioTrans{copyright} to simulate groundwater flow, solute transport, and oxygen-limited, multi-species biodegradation. Regional flow evaluation, detailed model sensitivity analyses, and subarea modeling were employed to provide support to model predictions. Predictions will be tested by subsequent progress and compliance monitoring. Site closure began in early 1996.

  12. Intrinsic motivation and amotivation in first episode and prolonged psychosis.

    PubMed

    Luther, Lauren; Lysaker, Paul H; Firmin, Ruth L; Breier, Alan; Vohs, Jenifer L

    2015-12-01

    The deleterious functional implications of motivation deficits in psychosis have generated interest in examining dimensions of the construct. However, there remains a paucity of data regarding whether dimensions of motivation differ over the course of psychosis. Therefore, this study examined two motivation dimensions, trait-like intrinsic motivation, and the negative symptom of amotivation, and tested the impact of illness phase on the 1) levels of these dimensions and 2) relationship between these dimensions. Participants with first episode psychosis (FEP; n=40) and prolonged psychosis (n=66) completed clinician-rated measures of intrinsic motivation and amotivation. Analyses revealed that when controlling for group differences in gender and education, the FEP group had significantly more intrinsic motivation and lower amotivation than the prolonged psychosis group. Moreover, intrinsic motivation was negatively correlated with amotivation in both FEP and prolonged psychosis, but the magnitude of the relationship did not statistically differ between groups. These findings suggest that motivation deficits are more severe later in the course of psychosis and that low intrinsic motivation may be partially independent of amotivation in both first episode and prolonged psychosis. Clinically, these results highlight the importance of targeting motivation in early intervention services. PMID:26386901

  13. A Comparison of Two Objective Measures of Binaural Processing: The Interaural Phase Modulation Following Response and the Binaural Interaction Component.

    PubMed

    Haywood, Nicholas R; Undurraga, Jaime A; Marquardt, Torsten; McAlpine, David

    2015-01-01

    There has been continued interest in clinical objective measures of binaural processing. One commonly proposed measure is the binaural interaction component (BIC), which is obtained typically by recording auditory brainstem responses (ABRs)-the BIC reflects the difference between the binaural ABR and the sum of the monaural ABRs (i.e., binaural - (left + right)). We have recently developed an alternative, direct measure of sensitivity to interaural time differences, namely, a following response to modulations in interaural phase difference (the interaural phase modulation following response; IPM-FR). To obtain this measure, an ongoing diotically amplitude-modulated signal is presented, and the interaural phase difference of the carrier is switched periodically at minima in the modulation cycle. Such periodic modulations to interaural phase difference can evoke a steady state following response. BIC and IPM-FR measurements were compared from 10 normal-hearing subjects using a 16-channel electroencephalographic system. Both ABRs and IPM-FRs were observed most clearly from similar electrode locations-differential recordings taken from electrodes near the ear (e.g., mastoid) in reference to a vertex electrode (Cz). Although all subjects displayed clear ABRs, the BIC was not reliably observed. In contrast, the IPM-FR typically elicited a robust and significant response. In addition, the IPM-FR measure required a considerably shorter recording session. As the IPM-FR magnitude varied with interaural phase difference modulation depth, it could potentially serve as a correlate of perceptual salience. Overall, the IPM-FR appears a more suitable clinical measure than the BIC. PMID:26721925

  14. Pair breaking and ``intrinsic`` {Tc}

    SciTech Connect

    Wolf, S.A.; Kresin, V.Z.; Ovchinnikov, Y.N.

    1996-12-31

    An analysis of the temperature dependence of the upper critical field in several cuprate families leads to the conclusion that magnetic impurities are present even in samples with the maximum observed value of T{sub c}. A new parameter, intrinsic T{sub c} (T{sub c;intr}) which is its value in the absence of magnetic impurities, is introduced. The maximum value of T{sub c;intr}, which corresponds to the maximum doping level, appears to be similar for different cuprates and to be equal to 160--170 K. This is an upper limit of T{sub c} in the cuprates.

  15. Nuclear Filtering of Intrinsic Charm

    SciTech Connect

    Kopeliovich, B. Z.; Potashnikova, I. K.; Schmidt, Ivan

    2010-11-12

    Nuclei are transparent for a heavy intrinsic charm (IC) component of the beam hadrons, what leads to an enhanced nuclear dependence of open charm production at large Feynman x{sub F}. Indeed, such an effect is supported by data from the SELEX experiment published recently [1]. Our calculations reproduce well the data, providing strong support for the presence of IC in hadrons in amount less than 1%. Moreover, we performed an analysis of nuclear effects in J/{Psi} production and found at large x{sub F} a similar, albeit weaker effect, which does not contradict data.

  16. The Effect of Oxandrolone on the Endocrinologic, Inflammatory, and Hypermetabolic Responses During the Acute Phase Postburn

    PubMed Central

    Jeschke, Marc G.; Finnerty, Celeste C.; Suman, Oscar E.; Kulp, Gabriela; Mlcak, Ronald P.; Herndon, David N.

    2007-01-01

    Objective and Summary Background Data: Postburn long-term oxandrolone treatment improves hypermetabolism and body composition. The effects of oxandrolone on clinical outcome, body composition, endocrine system, and inflammation during the acute phase postburn in a large prospective randomized single-center trial have not been studied. Methods: Burned children (n = 235) with >40% total body surface area burn were randomized (block randomization 4:1) to receive standard burn care (control, n = 190) or standard burn care plus oxandrolone for at least 7 days (oxandrolone 0.1 mg/kg body weight q.12 hours p.o, n = 45). Clinical parameters, body composition, serum hormones, and cytokine expression profiles were measured throughout acute hospitalization. Statistical analysis was performed by Student t test, or ANOVA followed by Bonferroni correction with significance accepted at P < 0.05. Results: Demographics and clinical data were similar in both groups. Length of intensive care unit stay was significantly decreased in oxandrolone-treated patients (0.48 ± 0.02 days/% burn) compared with controls (0.56 ± 0.02 days/% burn), (P < 0.05). Control patients lost 8 ± 1% of their lean body mass (LBM), whereas oxandrolone-treated patients had preserved LBM (+9 ± 4%), P < 0.05. Oxandrolone significantly increased serum prealbumin, total protein, testosterone, and AST/ALT, whereas it significantly decreased α2-macroglobulin and complement C3, P < 0.05. Oxandrolone did not adversely affect the endocrine and inflammatory response as we found no significant differences in the hormone panels and cytokine expression profiles. Conclusions: In this large prospective, double-blinded, randomized single-center study, oxandrolone shortened length of acute hospital stay, maintained LBM, improved body composition and hepatic protein synthesis while having no adverse effects on the endocrine axis postburn, but was associated with an increase in AST and ALT. PMID:17717439

  17. Acute-phase responses in cattle infected with hydatid cysts and microbial agents.

    PubMed

    Sevimli, A; Sevimli, F K; Şeker, E; Ulucan, A; Demirel, H H

    2015-07-01

    The aim of this study was to investigate the effect of hydatid cysts and microbial agents on the acute-phase response in cattle. Twenty-seven cattle with hydatid cysts and eight apparently healthy cattle comprised the study and control groups, respectively. Parasitological, microbiological, histopathological and immunohistochemical examinations of the liver and lungs were undertaken, and 49 of these organs were infected with cysts. In 14 of 31 (45.1%) livers and 10 of 18 (55.5%) lungs microbial growth was observed. The most frequent species occurring in the liver were Staphylococcus aureus, Escherichia coli, Corynebacterium spp. and Campylobacter spp., whereas in the lungs the most common species was Candida spp., followed by Streptococcus spp., Mannheimia haemolytica, Corynebacterium spp., Micrococcus spp. and S. aureus. The concentration of serum interleukin (IL-6) in infected cattle, 455.35 ± 39.68 pg/ml, was significantly higher than that of 83.02 ± 17.87 pg/ml in the control group (P0.05). The highest concentrations of IL-6 were detected in serum of the cattle where microbial growth had been detected, followed by cattle infected with bacteria + Trichostrongylus sp. (P< 0.001). Consequently, SAA showed an important increase in the group infected with hydatid cysts, whereas haptoglobin level decreased. It was noticed that IL-6, like SAA, had a significant role in hydatid cyst infection. Therefore IL-6 and SAA appear to be major markers in the detection of infection of cattle with hydatid cysts. PMID:26017333

  18. Intrinsic defect formation in peptide self-assembly

    NASA Astrophysics Data System (ADS)

    Deng, Li; Zhao, Yurong; Xu, Hai; Wang, Yanting

    2015-07-01

    In contrast to extensively studied defects in traditional materials, we report here a systematic investigation of the formation mechanism of intrinsic defects in self-assembled peptide nanostructures. The Monte Carlo simulations with our simplified dynamic hierarchical model revealed that the symmetry breaking of layer bending mode at the two ends during morphological transformation is responsible for intrinsic defect formation, whose microscopic origin is the mismatch between layer stacking along the side-chain direction and layer growth along the hydrogen bond direction. Moreover, defect formation does not affect the chirality of the self-assembled structure, which is determined by the initial steps of the peptide self-assembly process.

  19. STAT3 Activation in Skeletal Muscle Links Muscle Wasting and the Acute Phase Response in Cancer Cachexia

    PubMed Central

    Kunzevitzky, Noelia; Guttridge, Denis C.; Khuri, Sawsan; Koniaris, Leonidas G.; Zimmers, Teresa A.

    2011-01-01

    Background Cachexia, or weight loss despite adequate nutrition, significantly impairs quality of life and response to therapy in cancer patients. In cancer patients, skeletal muscle wasting, weight loss and mortality are all positively associated with increased serum cytokines, particularly Interleukin-6 (IL-6), and the presence of the acute phase response. Acute phase proteins, including fibrinogen and serum amyloid A (SAA) are synthesized by hepatocytes in response to IL-6 as part of the innate immune response. To gain insight into the relationships among these observations, we studied mice with moderate and severe Colon-26 (C26)-carcinoma cachexia. Methodology/Principal Findings Moderate and severe C26 cachexia was associated with high serum IL-6 and IL-6 family cytokines and highly similar patterns of skeletal muscle gene expression. The top canonical pathways up-regulated in both were the complement/coagulation cascade, proteasome, MAPK signaling, and the IL-6 and STAT3 pathways. Cachexia was associated with increased muscle pY705-STAT3 and increased STAT3 localization in myonuclei. STAT3 target genes, including SOCS3 mRNA and acute phase response proteins, were highly induced in cachectic muscle. IL-6 treatment and STAT3 activation both also induced fibrinogen in cultured C2C12 myotubes. Quantitation of muscle versus liver fibrinogen and SAA protein levels indicates that muscle contributes a large fraction of serum acute phase proteins in cancer. Conclusions/Significance These results suggest that the STAT3 transcriptome is a major mechanism for wasting in cancer. Through IL-6/STAT3 activation, skeletal muscle is induced to synthesize acute phase proteins, thus establishing a molecular link between the observations of high IL-6, increased acute phase response proteins and muscle wasting in cancer. These results suggest a mechanism by which STAT3 might causally influence muscle wasting by altering the profile of genes expressed and translated in muscle such

  20. Effect Anticipation Affects Perceptual, Cognitive, and Motor Phases of Response Preparation: Evidence from an Event-Related Potential (ERP) Study

    PubMed Central

    Harrison, Neil R.; Ziessler, Michael

    2016-01-01

    The anticipation of action effects is a basic process that can be observed even for key-pressing responses in a stimulus-response paradigm. In Ziessler et al.’s (2012) experiments participants first learned arbitrary effects of key-pressing responses. In the test phase an imperative stimulus determined the response, but participants withheld the response until a Go-stimulus appeared. Reaction times (RTs) were shorter if the Go-stimulus was compatible with the learned response effect. This is strong evidence that effect representations were activated during response planning. Here, we repeated the experiment using event-related potentials (ERPs), and we found that Go-stimulus locked ERPs depended on the compatibility relationship between the Go-stimulus and the response effect. In general, this supports the interpretation of the behavioral data. More specifically, differences in the ERPs between compatible and incompatible Go-stimuli were found for the early perceptual P1 component and the later frontal P2 component. P1 differences were found only in the second half of the experiment and for long stimulus onset asynchronies (SOAs) between imperative stimulus and Go-stimulus, i.e., when the effect was fully anticipated and the perceptual system was prepared for the effect-compatible Go-stimulus. P2 amplitudes, likely associated with evaluation and conflict detection, were larger when Go-stimulus and effect were incompatible; presumably, incompatibility increased the difficulty of effect anticipation. Onset of response-locked lateralized readiness potentials (R-LRPs) occurred earlier under incompatible conditions indicating extended motor processing. Together, these results strongly suggest that effect anticipation affects all (i.e., perceptual, cognitive, and motor) phases of response preparation. PMID:26858621

  1. Intrinsic motivation and attentional capture from gamelike features in a visual search task.

    PubMed

    Miranda, Andrew T; Palmer, Evan M

    2014-03-01

    In psychology research studies, the goals of the experimenter and the goals of the participants often do not align. Researchers are interested in having participants who take the experimental task seriously, whereas participants are interested in earning their incentive (e.g., money or course credit) as quickly as possible. Creating experimental methods that are pleasant for participants and that reward them for effortful and accurate data generation, while not compromising the scientific integrity of the experiment, would benefit both experimenters and participants alike. Here, we explored a gamelike system of points and sound effects that rewarded participants for fast and accurate responses. We measured participant engagement at both cognitive and perceptual levels and found that the point system (which invoked subtle, anonymous social competition between participants) led to positive intrinsic motivation, while the sound effects (which were pleasant and arousing) led to attentional capture for rewarded colors. In a visual search task, points were awarded after each trial for fast and accurate responses, accompanied by short, pleasant sound effects. We adapted a paradigm from Anderson, Laurent, and Yantis (Proceedings of the National Academy of Sciences 108(25):10367-10371, 2011b), in which participants completed a training phase during which red and green targets were probabilistically associated with reward (a point bonus multiplier). During a test phase, no points or sounds were delivered, color was irrelevant to the task, and previously rewarded targets were sometimes presented as distractors. Significantly longer response times on trials in which previously rewarded colors were present demonstrated attentional capture, and positive responses to a five-question intrinsic-motivation scale demonstrated participant engagement. PMID:23835649

  2. Lack of association of acute phase response proteins with hormone levels and antidepressant medication in perimenopausal depression

    PubMed Central

    2014-01-01

    Background Major depression is associated with higher plasma levels of positive acute-phase proteins, as well as with lower plasma levels of negative acute-phase proteins. The aim of this study is to examine the levels of acute-phase response proteins and whether these levels are influenced by reproductive hormones and antidepressant medication in the perimenopausal depression. Methods Sixty-five women (age range: 40–58 years old) participated in this study. All women were in the perimenopausal phase. The diagnosis of depression was made through a psychiatric interview and with the aid of Hamilton Depression Rating Scale 17 (HAM-D 17). The acute-phase response proteins, such as haptoglobin (HP), transferrine (TRf), α1-antitrypsin, complement protein 3 (C3), complement protein 4 (C4) and C-reactive protein (CRP) and the reproductive hormones, for example follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2), were analyzed using standard laboratory methods. Pearson’s correlations were applied to evaluate the relationship between acute-phase proteins and hormones. Results Perimenopausal women were divided into three groups. The first group consisted of normal controls, the second one involved depressed perimenopausal women, who were taking selective serotonin reuptake inhibitors (SSRIs), and the third one included depressed women that were not treated with SSRIs. Depressed women in perimenopause, when being compared to non-depressed women, did not differ as to serum levels of acute-phase proteins. There was a positive correlation between HP and E2 in depressed perimenopausal women, who were not taking SSRIs. Conclusions The lack of association between acute-phase proteins and depressive mood mentioned in this study does not support previous findings in patients with major depression. This negative finding in perimenopausal depression indicates either the absence or a more complex nature of the interactions between acute-phase proteins

  3. Hyperbaric oxygen treatment produces an antinociceptive response phase and inhibits astrocyte activation and inflammatory response in a rat model of neuropathic pain.

    PubMed

    Zhao, Bai-Song; Meng, Ling-Xin; Ding, Yuan-Yuan; Cao, Yan-Yan

    2014-06-01

    Hyperbaric oxygen (HBO) treatment has been proven to be a promising candidate for protection of the nervous system after acute injury in animal models of neuropathic pain. The purposes of this study were to examine the antinociceptive response phase induced by HBO treatment in a model of neuropathic pain and to determine the dependence of the treatment's mechanism of alleviating neuropathic pain on the inhibition of spinal astrocyte activation. Neuropathic pain was induced in rats by chronic constriction injury of the sciatic nerve. Mechanical threshold and thermal latency were tested preoperatively and for 1 week postoperatively, four times daily at fixed time points. Methane dicarboxylic aldehyde (MDA) and superoxide dismutase (SOD) parameters were used as indices of oxidative stress response and tested before and after the treatment. The inflammatory cytokines interleukin (IL)-1β and IL-10 were assayed in the sciatic nerve were with enzyme-linked immunoassay. Glial fibrillary acidic protein activation in the spinal cord was evaluated immunohistochemically. The rats exhibited temporary allodynia immediately after HBO treatment completion. This transient allodynia was closely associated with changes in MDA and SOD levels. A single HBO treatment caused a short-acting antinociceptive response phase. Repetitive HBO treatment led to a long-acting antinociceptive response phase and inhibited astrocyte activation. These results indicated that HBO treatment played a dual role in the aggravation and alleviation of neuropathic pain, though the aggravated pain effect (transient allodynia) was far less pronounced than the antinociceptive phase. Astrocyte inhibition and anti-inflammation may contribute to the antinociceptive effect of HBO treatment after nerve injury. PMID:24390961

  4. Lack of acute phase response in the livers of mice exposed to diesel exhaust particles or carbon black by inhalation

    PubMed Central

    Saber, Anne T; Halappanavar, Sabina; Folkmann, Janne K; Bornholdt, Jette; Boisen, Anne Mette Z; Møller, Peter; Williams, Andrew; Yauk, Carole; Vogel, Ulla; Loft, Steffen; Wallin, Håkan

    2009-01-01

    Background Epidemiologic and animal studies have shown that particulate air pollution is associated with increased risk of lung and cardiovascular diseases. Although the exact mechanisms by which particles induce cardiovascular diseases are not known, studies suggest involvement of systemic acute phase responses, including C-reactive protein (CRP) and serum amyloid A (SAA) in humans. In this study we test the hypothesis that diesel exhaust particles (DEP) – or carbon black (CB)-induced lung inflammation initiates an acute phase response in the liver. Results Mice were exposed to filtered air, 20 mg/m3 DEP or CB by inhalation for 90 minutes/day for four consecutive days; we have previously shown that these mice exhibit pulmonary inflammation (Saber AT, Bornholdt J, Dybdahl M, Sharma AK, Loft S, Vogel U, Wallin H. Tumor necrosis factor is not required for particle-induced genotoxicity and pulmonary inflammation., Arch. Toxicol. 79 (2005) 177–182). As a positive control for the induction of an acute phase response, mice were exposed to 12.5 mg/kg of lipopolysaccharide (LPS) intraperitoneally. Quantitative real time RT-PCR was used to examine the hepatic mRNA expression of acute phase proteins, serum amyloid P (Sap) (the murine homologue of Crp) and Saa1 and Saa3. While significant increases in the hepatic expression of Sap, Saa1 and Saa3 were observed in response to LPS, their levels did not change in response to DEP or CB. In a comprehensive search for markers of an acute phase response, we analyzed liver tissue from these mice using high density DNA microarrays. Globally, 28 genes were found to be significantly differentially expressed in response to DEP or CB. The mRNA expression of three of the genes (serine (or cysteine) proteinase inhibitor, clade A, member 3C, apolipoprotein E and transmembrane emp24 domain containing 3) responded to both exposures. However, these changes were very subtle and were not confirmed by real time RT-PCR. Conclusion Our findings

  5. Modulation of spatial and response strategies by phase of the menstrual cycle in women tested in a virtual navigation task.

    PubMed

    Hussain, Dema; Hanafi, Sarah; Konishi, Kyoko; Brake, Wayne G; Bohbot, Véronique D

    2016-08-01

    Different memory systems are employed to navigate an environment. It has been consistently shown in rodents that estrogen impacts multiple memory system bias such that low estradiol (E2) is associated with increased use of a striatal-mediated response strategy whereas high E2 increases use of a hippocampal-dependent spatial memory. Low E2 also enhances performance on a response-based task whereas high E2 levels improve learning on a spatial task. The purpose of the present cross-sectional study was to investigate navigational strategies in young, healthy, naturally cycling women. Participants were split into either an early follicular (i.e., when E2 levels are low), ovulatory (i.e., when E2 levels are high) or mid/late luteal (i.e., end of the cycle, when E2 levels decrease and progesterone levels rise) phase group, using self-reported date of the menstrual cycle. Serum hormone level measurements (E2, progesterone, testosterone) were used to confirm cycle phase assignment. Participants were administered a verbal memory task as well as a virtual navigation task that can be solved by using either a response or spatial strategy. Women tested in the ovulatory phase, under high E2 conditions, performed better on a verbal memory task than women tested during the other phases of the cycle. Interestingly, women tested in the mid/late luteal phase, when progesterone is high, predominantly used a spatial strategy, whereas the opposite pattern was observed in the early follicular and ovulatory groups. Our data suggest that the specific memory system engaged differs depending on the phase of the menstrual cycle and may be mediated by both E2 and progesterone, rather than E2 alone. PMID:27213559

  6. Predictors of Longitudinal Outcomes after Unstable Response to Acute Phase Cognitive Therapy for Major Depressive Disorder

    PubMed Central

    Vittengl, Jeffrey R.; Clark, Lee Anna; Thase, Michael E.; Jarrett, Robin B.

    2015-01-01

    After patients with major depressive disorder (MDD) respond to acute-phase cognitive therapy (CT), continuation-phase treatments may be applied to improve long-term outcomes. We clarified which CT responders experience remission, recovery, relapse, and recurrence by testing baseline demographic, clinical, and personality variables. The sample of CT responders at higher risk of relapse (N = 241) was randomized to 8 months of continuation-phase CT (C-CT), double-blinded fluoxetine or pill placebo, and followed 24 months (Jarrett & Thase, 2010). Patients with lower positive emotionality and behavioral activation at the end of acute-phase CT showed increased risk for relapse/recurrence of MDD. In addition, patients with lower positive emotionality and behavioral activation, as well as higher residual depression (including emotional, cognitive, and social facets), showed decreased probability of remission (≥6 continuous weeks of minimal or absent symptoms) after acute-phase CT. Finally, patients with greater residual depression, as well as younger age and earlier MDD onset, showed decreased probability of recovery (≥35 continuous weeks of minimal or absent symptoms) after acute-phase CT. Moderator analyses did not reveal differential prediction across the continuation phase treatment arms. These results may help clinicians gauge the prognoses and need for continuation treatment among MDD patients who respond to acute-phase CT. PMID:25985046

  7. FUMIGANT USE IN CALIFORNIA – RESPONSE TO THE PHASE-OUT

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Pesticide Use Reporting (PUR) requirements in California allow tracking of the uses of methyl bromide (MeBr) and alternative fumigants during the MeBr phase-out. Use of MeBr declined gradually between 1991 and 1999, the first year of the phase-out. In 2000 and 2001, use dropped dramatically to b...

  8. Analysis of Cell Cycle Phase Response Captures the Synchronization Phenomena and Reveals a Novel Cell Cycle Network Topology

    NASA Astrophysics Data System (ADS)

    Li, Ying; Lin, Yihan; Scherer, Norbert; Dinner, Aaron

    2011-03-01

    Cell cycle progression requires a succession of temporally-regulated sub-processes, including chromosome replication and cell division, which are each controlled by their own regulatory modules. The modular design of cell cycle regulatory network allows robust environmental responses and evolutionary adaptations. It is emerging that some of the cell cycle modules involve their own autonomous periodic dynamics. As a consequence, the realization of robust coordination among these modules becomes challenging since each module could potentially run out of sync. We believe that an insight into this puzzle resides in the coupling between the contributing regulatory modules. Here, we measured the phase response curve (PRC) of the cell cycle oscillator by driving the expression of a master regulator of the cell cycle in a pulsatile manner and measuring the single cell phase response. We constructed a return map that quantitatively explains the synchronization phenomena that were caused by periodic chemical perturbation. To capture the measured phase response, we derived a minimalist coupled oscillator model that generalizes the basic topology of the cell cycle network. This diode-like coupling suggests that the cell is engineered to ensure complete coordination of constituent events with the cell cycle.

  9. Li-ion battery shut-off at high temperature caused by polymer phase separation in responsive electrolytes.

    PubMed

    Kelly, Jesse C; Degrood, Nicholas L; Roberts, Mark E

    2015-03-28

    For the purpose of realizing inherently safe high-power Li-ion batteries, a model Li4Ti5O12/LiFePO4 rechargeable battery is investigated using the thermally responsive polymer, poly(benzyl methacrylate), in an ionic liquid. At high temperature, battery operation is inhibited as a result of increased internal resistance caused by polymer and ionic liquid phase separation. Li-ion concentration is shown to affect the phase transition temperature and the extent to which batteries are deactivated. PMID:25731742

  10. Metabolizable protein supply modulated the acute-phase response following vaccination of beef steers.

    PubMed

    Moriel, P; Arthington, J D

    2013-12-01

    Our objective was to evaluate the effects of MP supply, through RUP supplementation, on the acute-phase response of beef steers following vaccination. On d 0, Brangus-crossbred steers (n = 24; 173 ± 31 kg; 175 ± 16 d of age) were randomly assigned to receive 1 of 3 isocaloric diets formulated to provide 85, 100, and 115% of the daily MP requirements of a beef steer gaining 0.66 kg of BW daily. Diets were limit-fed at 1.8% of BW (DM basis) and individually provided to steers once daily (0800 h) from d 0 to 29. Steers were weighed on d 0 and 29, following a 12-h period of feed and water withdrawal. On d 7, steers were vaccinated against Mannheimia haemolytica (OneShot, Pfizer), and blood samples were collected on d 0, 7, 8, 10, 14, 21, and 30. Plasma metabolites were analyzed as repeated measures using the MIXED procedure of SAS. Final BW and ADG were similar (P ≥ 0.50) among treatments (mean = 184 ± 9 kg and 0.5 ± 0.08 kg/d, respectively). Effects of time were detected (P < 0.01) for plasma concentrations of all acute-phase proteins, which peaked between d 7 to 14, returning to baseline concentrations by d 29. Treatment effects were not detected (P ≥ 0.19) for plasma concentrations of acid-soluble protein, albumin, fibrinogen, IGF-1 and serum amyloid-A. Plasma concentrations of total protein (TP) and plasma urea nitrogen (PUN) increased (P ≤ 0.05) with increasing supply of MP (87.1, 89.6, and 90.1 ± 1.09 mg TP/mL and 6.1, 8.3, and 10.3 ± 0.41 mg PUN/dL for 85, 100, and 115% MP steers, respectively). From d 10 to 29, steers provided 115% MP had less (P < 0.001) plasma concentrations of ceruloplasmin than steers fed 85 and 100% MP, which had similar plasma ceruloplasmin concentrations. On d 14, plasma concentrations of haptoglobin were greatest (P ≤ 0.06) for steers fed 115% MP, intermediate for 100% MP, and least for 85% MP (0.98, 0.71 and 0.44 ± 0.099 mg/mL, respectively). On d 10, plasma concentrations of creatinine were greater (P = 0.01) for steers

  11. Intrinsic relationship between electronic structures and phase transition of SrBi{sub 2−x}Nd{sub x}Nb{sub 2}O{sub 9} ceramics from ultraviolet ellipsometry at elevated temperatures

    SciTech Connect

    Duan, Z. H.; Jiang, K.; Xu, L. P.; Li, Y. W.; Hu, Z. G. Chu, J. H.

    2014-02-07

    The ferroelectric orthorhombic to paraelectric tetragonal phase transition of SrBi{sub 2−x}Nd{sub x}Nb{sub 2}O{sub 9} (x = 0, 0.05, 0.1, and 0.2) layer-structured ceramics has been investigated by temperature-dependent spectroscopic ellipsometry. Based on the analysis of dielectric functions from 0 to 500 °C with double Tauc-Lorentz dispersion model, the interband transitions located at ultraviolet region have shown an abrupt variation near the Curie temperature. The changes of dielectric functions are mainly due to the thermal-optical and/or photoelastic effect. Moreover, the characteristic alteration in interband transitions can be ascribed to distortion of NbO{sub 6} octahedron and variation of hybridization between Bi 6s and O 2p states during the structure transformation.

  12. Suppression of DHEA sulfotransferase (Sult2A1) during the acute-phase response.

    PubMed

    Kim, Min Sun; Shigenaga, Judy; Moser, Art; Grunfeld, Carl; Feingold, Kenneth R

    2004-10-01

    The acute-phase response (APR) induces alterations in lipid metabolism, and our data suggest that this is associated with suppression of type II nuclear hormone receptors that are key regulators of fatty acid, cholesterol, and bile acid metabolism. Recently, the farnesoid X receptor (FXR), constitutive androstane receptor (CAR), and pregnane X receptor (PXR) were found to regulate DHEA sulfotransferase (Sult2A1), which plays an important role in DHEA sulfation and detoxification of bile acids. Because FXR, PXR, and CAR are suppressed during the APR, we hypothesized that Sult2A1 is downregulated during the APR. To induce the APR, mice were treated with LPS, which will then trigger the release of various cytokines, and the mRNA levels of Sult2A1 and the sulfate donor 3'-phosphoadenosine 5'-phosphosulfate synthase 2 (PAPSS2), as well as the enzyme activity of Sult2A1, were determined in the liver. We found that mRNA levels of Sult2A1 decrease in a time- and dose-dependent manner during the LPS-induced APR. Similar changes were observed in the mRNA levels of PAPSS2, the major synthase of PAPS in the liver. Moreover, hepatic Sult2A1 activity and serum levels of DHEA-sulfate (DHEA-S) were significantly decreased in LPS-treated animals. These results suggest that decreased levels or activities of FXR, PXR, and CAR during the APR could contribute to decreases in Sult2A1, resulting in decreased sulfation of DHEA and lower circulating level of DHEA-S. Finally, we found that both TNF and IL-1 caused a significant decrease in the mRNA level of Sult2A1 in Hep3B human hepatoma cells, suggesting that the proinflammatory cytokines TNF and IL-1 mediate the inhibitory effect of LPS on Sult2A1 mRNA level. Our study provides a possible mechanism by which infection and inflammation are associated with altered steroid metabolism and cholestasis. PMID:15198932

  13. Systemic acute phase proteins response in calves experimentally infected with Eimeria zuernii.

    PubMed

    Lassen, Brian; Bangoura, Berit; Lepik, Triin; Orro, Toomas

    2015-09-15

    Acute phase proteins (APPs) have been demonstrated to be useful in evaluating general health stress and diseases in cattle. Serum amyloid A (SAA) and haptoglobin (Hp) are APPs that are produced during inflammation, and likely play a role in host immunological defence against Eimeria infection and the associated intestinal tissue damage. We investigated the involvement of SAA and HP in an experimental study, including three groups of calves: a control group (group 0, n=11), and two groups infected with either 150,000 or 250,000 Eimeria zuernii oocysts (group 1 (n=11) and group 2 (n=12), respectively). The calves were monitored for 28 days and data was collected on oocyst excretion, faecal score, animal weight, and SAA and Hp serum concentrations. Generalized linear mixed models showed that the clinical symptoms, indicated by an increase in the number of oocysts in the faeces and severe diarrhoea, manifested at patency for group 1 and 2. Serum Hp and SAA levels also increased during this period. Hp appeared to be a more sensitive marker than SAA, and differences between groups 1 and 2 were observed only for Hp. Linear regression models showed a negative association between weight gain and Hp concentrations, calculated as the area under the curve (AUC) during the overall experimental period and the patency period. A similar result was seen for SAA only during the patency period. This result supports the assumption that reduced weight gain due to E. zuernii infection is an immunologically driven process that involves an increase in APPs. A random intercept regression model of oocyst shedding groups showed that calves shedding 1-500 oocysts had reduced concentrations of Hp, indicating that a different immunological reaction occurs during mild shedding of E. zuernii oocysts than during more intensive shedding. A similar model was used to examine associations between faecal scores and Hp concentrations for each group. Group 2 calves with haemorrhagic diarrhoea displayed

  14. Electronic structure of intrinsic defects in crystalline germanium telluride.

    SciTech Connect

    Thompson, Aidan Patrick; Pineda, Andrew C.; Umrigar, Cyrus J.; Hjalmarson, Harold Paul; Schultz, Peter Andrew; Edwards, Arthur H.; Martin, Marcus Gary

    2005-05-01

    Germanium telluride undergoes rapid transition between polycrystalline and amorphous states under either optical or electrical excitation. While the crystalline phases are predicted to be semiconductors, polycrystalline germanium telluride always exhibits p-type metallic conductivity. We present a study of the electronic structure and formation energies of the vacancy and antisite defects in both known crystalline phases. We show that these intrinsic defects determine the nature of free-carrier transport in crystalline germanium telluride. Germanium vacancies require roughly one-third the energy of the other three defects to form, making this by far the most favorable intrinsic defect. While the tellurium antisite and vacancy induce gap states, the germanium counterparts do not. A simple counting argument, reinforced by integration over the density of states, predicts that the germanium vacancy leads to empty states at the top of the valence band, thus giving a complete explanation of the observed p-type metallic conduction.

  15. Sepsis chronically in MARS: systemic cytokine responses are always mixed regardless of the outcome, magnitude, or phase of sepsis.

    PubMed

    Osuchowski, Marcin F; Craciun, Florin; Weixelbaumer, Katrin M; Duffy, Elizabeth R; Remick, Daniel G

    2012-11-01

    The paradigm of systemic inflammatory response syndrome-to-compensatory anti-inflammatory response syndrome transition implies that hyperinflammation triggers acute sepsis mortality, whereas hypoinflammation (release of anti-inflammatory cytokines) in late sepsis induces chronic deaths. However, the exact humoral inflammatory mechanisms attributable to sepsis outcomes remain elusive. In the first part of this study, we characterized the systemic dynamics of the chronic inflammation in dying (DIE) and surviving (SUR) mice suffering from cecal ligation and puncture sepsis (days 6-28). In the second part, we combined the current chronic and previous acute/chronic sepsis data to compare the outcome-dependent inflammatory signatures between these two phases. A composite cytokine score (CCS) was calculated to compare global inflammatory responses. Mice were never sacrificed but were sampled daily (20 μl) for blood. In the first part of the study, parameters from chronic DIE mice were clustered into the 72, 48, and 24 h before death time points and compared with SUR of the same post-cecal ligation and puncture day. Cytokine increases were mixed and never preceded chronic deaths earlier than 48 h (3- to 180-fold increase). CCS demonstrated simultaneous and similar upregulation of proinflammatory and anti-inflammatory compartments at 24 h before chronic death (DIE 80- and 50-fold higher versus SUR). In the second part of the study, cytokine ratios across sepsis phases/outcomes indicated steady proinflammatory versus anti-inflammatory balance. CCS showed the inflammatory response in chronic DIE was 5-fold lower than acute DIE mice, but identical to acute SUR. The systemic mixed anti-inflammatory response syndrome-like pattern (concurrent release of proinflammatory and anti-inflammatory cytokines) occurs irrespective of the sepsis phase, response magnitude, and/or outcome. Although different in magnitude, neither acute nor chronic septic mortality is associated with a

  16. Intrinsic rotation with gyrokinetic models

    SciTech Connect

    Parra, Felix I.; Barnes, Michael; Catto, Peter J.; Calvo, Ivan

    2012-05-15

    The generation of intrinsic rotation by turbulence and neoclassical effects in tokamaks is considered. To obtain the complex dependences observed in experiments, it is necessary to have a model of the radial flux of momentum that redistributes the momentum within the tokamak in the absence of a preexisting velocity. When the lowest order gyrokinetic formulation is used, a symmetry of the model precludes this possibility, making small effects in the gyroradius over scale length expansion necessary. These effects that are usually small become important for momentum transport because the symmetry of the lowest order gyrokinetic formulation leads to the cancellation of the lowest order momentum flux. The accuracy to which the gyrokinetic equation needs to be obtained to retain all the physically relevant effects is discussed.

  17. Dasatinib treatment of chronic-phase chronic myeloid leukemia: analysis of responses according to preexisting BCR-ABL mutations

    PubMed Central

    Müller, Martin C.; Cortes, Jorge E.; Kim, Dong-Wook; Druker, Brian J.; Erben, Philipp; Pasquini, Ricardo; Branford, Susan; Hughes, Timothy P.; Radich, Jerald P.; Ploughman, Lynn; Mukhopadhyay, Jaydip

    2009-01-01

    Dasatinib is a BCR-ABL inhibitor with 325-fold higher potency than imatinib against unmutated BCR-ABL in vitro. Imatinib failure is commonly caused by BCR-ABL mutations. Here, dasatinib efficacy was analyzed in patients recruited to phase 2/3 trials with chronic-phase chronic myeloid leukemia with or without BCR-ABL mutations after prior imatinib. Among 1043 patients, 39% had a preexisting BCR-ABL mutation, including 48% of 805 patients with imatinib resistance or suboptimal response. Sixty-threedifferent BCR-ABL mutations affecting 49 amino acids were detected at baseline, with G250, M351, M244, and F359 most frequently affected. After 2 years of follow-up, dasatinib treatment of imatinib-resistant patients with or without a mutation resulted in notable response rates (complete cytogenetic response: 43% vs 47%) and durable progression-free survival (70% vs 80%). High response rates were achieved with different mutations except T315I, including highly imatinib-resistant mutations in the P-loop region. Impaired responses were observed with some mutations with a dasatinib median inhibitory concentration (IC50) greater than 3nM; among patients with mutations with lower or unknown IC50, efficacy was comparable with those with no mutation. Overall, dasatinib has durable efficacy in patients with or without BCR-ABL mutations. All trials were registered at http://www.clinicaltrials.gov as NCT00123474, NCT00101660, and NCT00103844. PMID:19779040

  18. Planar intrinsic Josephson junctions fabricated on Bi-2212 LPE films

    NASA Astrophysics Data System (ADS)

    Yasuda, Takashi; Kawae, Takeshi; Yamashita, Tsutomu; Taka, Chihiro; Nishida, Akihiko; Takano, Shuzo

    2003-05-01

    Planar design of intrinsic Josephson junctions (IJJs) is studied using Bi2Sr2CaCu2Ox (Bi-2212) films prepared by liquid phase epitaxy. Step-type IJJ stacks fabricated on step-patterned MgO substrates exhibit multibranched current-voltage characteristics inherent in Bi-2212 single crystals. This behavior is found to be limited to films on small-angle steps, suggesting the incorporation of defects near the steep steps of substrates.

  19. A method of investigating the phase response characteristic of the ionospheric scattering communications channel

    NASA Technical Reports Server (NTRS)

    Yakovets, A. F.

    1972-01-01

    A method is proposed for measuring the phase difference fluctuations between vibrations at different frequencies that result from scattering properties of the medium. The measurement equipment is described, along with an ideal communication channel.

  20. Phase-shift, stimuli-responsive drug carriers for targeted delivery

    PubMed Central

    O’Neill, Brian E; Rapoport, Natalya

    2011-01-01

    The intersection of particles and directed energy is a rich source of novel and useful technology that is only recently being realized for medicine. One of the most promising applications is directed drug delivery. This review focuses on phase-shift nanoparticles (that is, particles of submicron size) as well as micron-scale particles whose action depends on an external-energy triggered, first-order phase shift from a liquid to gas state of either the particle itself or of the surrounding medium. These particles have tremendous potential for actively disrupting their environment for altering transport properties and unloading drugs. This review covers in detail ultrasound and laser-activated phase-shift nano- and micro-particles and their use in drug delivery. Phase-shift based drug-delivery mechanisms and competing technologies are discussed. PMID:22059114

  1. Transcriptomic response of Listeria monocytogenes during the transition to the long-term-survival phase.

    PubMed

    Wen, Jia; Deng, Xiangyu; Li, Zengxin; Dudley, Edward G; Anantheswaran, Ramaswamy C; Knabel, Stephen J; Zhang, Wei

    2011-09-01

    Listeria monocytogenes can change its cellular morphology from bacilli to cocci during the transition to the long-term-survival (LTS) phase. The LTS cells demonstrated increased baro- and thermotolerance compared to their vegetative counterparts. So far, the underlying mechanisms that trigger this morphological and physiological transition remain largely unknown. In this study, we compared the transcriptomic profiles of L. monocytogenes serotype 4b strain F2365 at different growth stages in tryptic soy broth with yeast extract (TSBYE) using a whole-genome DNA chip approach. We identified a total of 225 differentially expressed genes (≥4-fold; P < 0.05) during the transition to the LTS phase in TSBYE. Genes related to cell envelope structure, energy metabolism, and transport were most significantly upregulated in the LTS phase. The upregulation of compatible solute transporters may lead to the accumulation of cellular solutes, lowering intracellular water activity and thus increasing bacterial stress resistance during the transition to the LTS phase. The downregulation of genes associated with protein synthesis may indicate a status of metabolic dormancy of the LTS cells. The transcriptomic profiles of resuscitated LTS cells in fresh TSBYE resembled those of log-phase cells (r=0.94), as the LTS cells rapidly resume metabolic activities and transit back to log phase with decreased baro- and thermotolerance. PMID:21764970

  2. Particle-Induced Pulmonary Acute Phase Response Correlates with Neutrophil Influx Linking Inhaled Particles and Cardiovascular Risk

    PubMed Central

    Saber, Anne Thoustrup; Lamson, Jacob Stuart; Jacobsen, Nicklas Raun; Ravn-Haren, Gitte; Hougaard, Karin Sørig; Nyendi, Allen Njimeri; Wahlberg, Pia; Madsen, Anne Mette; Jackson, Petra; Wallin, Håkan; Vogel, Ulla

    2013-01-01

    Background Particulate air pollution is associated with cardiovascular disease. Acute phase response is causally linked to cardiovascular disease. Here, we propose that particle-induced pulmonary acute phase response provides an underlying mechanism for particle-induced cardiovascular risk. Methods We analysed the mRNA expression of Serum Amyloid A (Saa3) in lung tissue from female C57BL/6J mice exposed to different particles including nanomaterials (carbon black and titanium dioxide nanoparticles, multi- and single walled carbon nanotubes), diesel exhaust particles and airborne dust collected at a biofuel plant. Mice were exposed to single or multiple doses of particles by inhalation or intratracheal instillation and pulmonary mRNA expression of Saa3 was determined at different time points of up to 4 weeks after exposure. Also hepatic mRNA expression of Saa3, SAA3 protein levels in broncheoalveolar lavage fluid and in plasma and high density lipoprotein levels in plasma were determined in mice exposed to multiwalled carbon nanotubes. Results Pulmonary exposure to particles strongly increased Saa3 mRNA levels in lung tissue and elevated SAA3 protein levels in broncheoalveolar lavage fluid and plasma, whereas hepatic Saa3 levels were much less affected. Pulmonary Saa3 expression correlated with the number of neutrophils in BAL across different dosing regimens, doses and time points. Conclusions Pulmonary acute phase response may constitute a direct link between particle inhalation and risk of cardiovascular disease. We propose that the particle-induced pulmonary acute phase response may predict risk for cardiovascular disease. PMID:23894396

  3. Induction of several acute-phase protein genes by heavy metals: A new class of metal-responsive genes

    SciTech Connect

    Yiangou, Minas; Ge, Xin; Carter, K.C.; Papaconstantinou, J. Shriners Burns Institute, Galveston, TX )

    1991-04-16

    Acute-phase reactants, metallothioneins, and heat-shock proteins are the products of three families of genes that respond to glucocorticoids and cytokines. Metallothioneins and heat-shock proteins, however, are also stimulated by heavy metals whereas very little is known about the effect of heavy metals on acute-phase-reactant genes. The authors have studied the effect of heavy metals (Hg, Cd, Pb, Cu, Ni, and Zn) and Mg on the acute-phase reactants {alpha}{sub 1}-acid glycoprotein, C-reactive protein, {alpha}{sub 1}-antitrypsin and {alpha}{sub 1}-antichymotrypsin. {alpha}{sub 1}-Acid glycoprotein and C-reactive protein mRNA levels were increased severalfold in livers of heavy-metal-treated Balb/c mice. The strongest induction was mediated by Hg, followed in order of response by Cd > Pb > Cu > Ni > Zn > Mg. None of the metals affected the mRNA levels of albumin, {alpha}{sub 1}-antitrypsin, and {alpha}{sub 1}-antichymotrypsin. Furthermore, failure to repress albumin, a negative acute-phase reactant, indicated that the induction of these genes was not due to a metal-mediated inflammatory response. The metals also induced {alpha}{sub 1}-acid glycoprotein and C-reactive protein in adrenalectomized animals, indicating that induction by the heavy metals is not mediated by the glucocorticoid induction pathway. Sequence analysis has revealed a region of homology to metal-responsive elements in the {alpha}{sub 1}-acid glycoprotein and C-reactive protein promoters. The studies indicate that the induction of {alpha}{sub 1}-acid glycoprotein and C-reactive protein by heavy metals may be regulated by these metal-responsive elements at the level of transcription.

  4. Toroidal modelling of RMP response in ASDEX Upgrade: coil phase scan, q 95 dependence, and toroidal torques

    NASA Astrophysics Data System (ADS)

    Liu, Yueqiang; Ryan, D.; Kirk, A.; Li, Li; Suttrop, W.; Dunne, M.; Fischer, R.; Fuchs, J. C.; Kurzan, B.; Piovesan, P.; Willensdorfer, M.; the ASDEX Upgrade Team; the EUROfusion MST1 Team

    2016-05-01

    The plasma response to the vacuum resonant magnetic perturbation (RMP) fields, produced by the ELM control coils in ASDEX Upgrade experiments, is computationally modelled using the MARS-F/K codes (Liu et al 2000 Phys. Plasmas 7 3681, Liu et al 2008 Phys. Plasmas 15 112503). A systematic investigation is carried out, considering various plasma and coil configurations as in the ELM control experiments. The low q plasmas, with {{q}95}∼ 3.8 (q 95 is the safety factor q value at 95% of the equilibrium poloidal flux), responding to low n (n is the toroidal mode number) field perturbations from each single row of the ELM coils, generates a core kink amplification effect. Combining two rows, with different toroidal phasing, thus leads to either cancellation or reinforcement of the core kink response, which in turn determines the poloidal location of the peak plasma surface displacement. The core kink response is typically weak for the n  =  4 coil configuration at low q, and for the n  =  2 configuration but only at high q ({{q}95}∼ 5.5 ). A phase shift of around 60 degrees for low q plasmas, and around 90 degrees for high q plasmas, is found in the coil phasing, between the plasma response field and the vacuum RMP field, that maximizes the edge resonant field component. This leads to an optimal coil phasing of about 100 (‑100) degrees for low (high) q plasmas, that maximizes both the edge resonant field component and the plasma surface displacement near the X-point of the separatrix. This optimal phasing closely corresponds to the best ELM mitigation observed in experiments. A strong parallel sound wave damping moderately reduces the core kink response but has minor effect on the edge peeling response. For low q plasmas, modelling shows that both the resonant electromagnetic torque and the neoclassical toroidal viscous (NTV) torque (due to the presence of 3D magnetic field perturbations) contribute to the toroidal flow damping, in particular near the

  5. Adaptive acid tolerance response of Vibrio parahaemolyticus as affected by acid adaptation conditions, growth phase, and bacterial strains.

    PubMed

    Chiang, Ming-Lun; Chou, Cheng-Chun; Chen, Hsi-Chia; Tseng, Yu-Ting; Chen, Ming-Ju

    2012-08-01

    Vibrio parahaemolyticus strain 690 was isolated from gastroenteritis patients. Its thermal and ethanol stress responses have been reported in our previous studies. In this study, we further investigated the effects of various acid adaptation conditions including pH (5.0-6.0) and time (30-90 min) on the acid tolerance in different growth phases of V. parahaemolyticus 690. Additionally, the adaptive acid tolerance among different V. parahaemolyticus strains was compared. Results indicated that the acid tolerance of V. parahaemolyticus 690 was significantly increased after acid adaptation at pH 5.5 and 6.0 for 30-90 min. Among the various acid adaptation conditions examined, V. parahaemolyticus 690 acid-adapted at pH 5.5 for 90 min exhibited the highest acid tolerance. The acid adaptation also influenced the acid tolerance of V. parahaemolyticus 690 in different growth phases with late-exponential phase demonstrating the greatest acid tolerance response (ATR) than other phases. Additionally, the results also showed that the induction of adaptive ATR varied with different strains of V. parahaemolyticus. An increase in acid tolerance of V. parahaemolyticus was observed after prior acid adaptation in five strains (556, 690, BCRC 13023, BCRC 13025, and BCRC 12864), but not in strains 405 and BCRC 12863. PMID:22827515

  6. Diverse precerebellar neurons share similar intrinsic excitability.

    PubMed

    Kolkman, Kristine E; McElvain, Lauren E; du Lac, Sascha

    2011-11-16

    The cerebellum dedicates a majority of the brain's neurons to processing a wide range of sensory, motor, and cognitive signals. Stereotyped circuitry within the cerebellar cortex suggests that similar computations are performed throughout the cerebellum, but little is known about whether diverse precerebellar neurons are specialized for the nature of the information they convey. In vivo recordings indicate that firing responses to sensory or motor stimuli vary dramatically across different precerebellar nuclei, but whether this reflects diverse synaptic inputs or differentially tuned intrinsic excitability has not been determined. We targeted whole-cell patch-clamp recordings to neurons in eight precerebellar nuclei which were retrogradely labeled from different regions of the cerebellum in mice. Intrinsic physiology was compared across neurons in the medial vestibular, external cuneate, lateral reticular, prepositus hypoglossi, supragenual, Roller/intercalatus, reticularis tegmenti pontis, and pontine nuclei. Within the firing domain, precerebellar neurons were remarkably similar. Firing faithfully followed temporally modulated inputs, could be sustained at high rates, and was a linear function of input current over a wide range of inputs and firing rates. Pharmacological analyses revealed common expression of Kv3 currents, which were essential for a wide linear firing range, and of SK (small-conductance calcium-activated potassium) currents, which were essential for a wide linear input range. In contrast, membrane properties below spike threshold varied considerably within and across precerebellar nuclei, as evidenced by variability in postinhibitory rebound firing. Our findings indicate that diverse precerebellar neurons perform similar scaling computations on their inputs but may be differentially tuned to synaptic inhibition. PMID:22090493

  7. Mice deficient of glutamatergic signaling from intrinsically photosensitive retinal ganglion cells exhibit abnormal circadian photoentrainment.

    PubMed

    Purrier, Nicole; Engeland, William C; Kofuji, Paulo

    2014-01-01

    Several aspects of behavior and physiology, such as sleep and wakefulness, blood pressure, body temperature, and hormone secretion exhibit daily oscillations known as circadian rhythms. These circadian rhythms are orchestrated by an intrinsic biological clock in the suprachiasmatic nuclei (SCN) of the hypothalamus which is adjusted to the daily environmental cycles of day and night by the process of photoentrainment. In mammals, the neuronal signal for photoentrainment arises from a small subset of intrinsically photosensitive retinal ganglion cells (ipRGCs) that send a direct projection to the SCN. ipRGCs also mediate other non-image-forming (NIF) visual responses such as negative masking of locomotor activity by light, and the pupillary light reflex (PLR) via co-release of neurotransmitters glutamate and pituitary adenylate cyclase-activating peptide (PACAP) from their synaptic terminals. The relative contribution of each neurotransmitter system for the circadian photoentrainment and other NIF visual responses is still unresolved. We investigated the role of glutamatergic neurotransmission for circadian photoentrainment and NIF behaviors by selective ablation of ipRGC glutamatergic synaptic transmission in mice. Mutant mice displayed delayed re-entrainment to a 6 h phase shift (advance or delay) in the light cycle and incomplete photoentrainment in a symmetrical skeleton photoperiod regimen (1 h light pulses between 11 h dark periods). Circadian rhythmicity in constant darkness also was reduced in some mutant mice. Other NIF responses such as the PLR and negative masking responses to light were also partially attenuated. Overall, these results suggest that glutamate from ipRGCs drives circadian photoentrainment and negative masking responses to light. PMID:25357191

  8. Developmental Effects of the ToxCast™ Phase I and Phase II Chemicals in Caenorhabditis elegans and Corresponding Responses in Zebrafish, Rats, and Rabbits

    PubMed Central

    Boyd, Windy A.; Smith, Marjolein V.; Co, Caroll A.; Pirone, Jason R.; Rice, Julie R.; Shockley, Keith R.; Freedman, Jonathan H.

    2015-01-01

    s potential toxicity to humans. Citation: Boyd WA, Smith MV, Co CA, Pirone JR, Rice JR, Shockley KR, Freedman JH. 2016. Developmental effects of the ToxCast™ Phase I and II chemicals in Caenorhabditis elegans and corresponding responses in zebrafish, rats, and rabbits. Environ Health Perspect 124:586–593; http://dx.doi.org/10.1289/ehp.1409645 PMID:26496690

  9. Postpartum Circulating Markers of Inflammation and the Systemic Acute-Phase Response After Early-Onset Preeclampsia.

    PubMed

    van Rijn, Bas B; Bruinse, Hein W; Veerbeek, Jan H; Post Uiterweer, Emiel D; Koenen, Steven V; van der Bom, Johanna G; Rijkers, Ger T; Roest, Mark; Franx, Arie

    2016-02-01

    Preeclampsia is an inflammatory-mediated hypertensive disorder of pregnancy and seems to be an early indicator of increased cardiovascular risk, but mechanisms underlying this association are unclear. In this study, we identified levels of circulating inflammatory markers and dynamic changes in the systemic acute-phase response in 44 women with a history of severe early-onset preeclampsia, compared with 29 controls with only uneventful pregnancies at 1.5 to 3.5 years postpartum. Models used were in vivo seasonal influenza vaccination and in vitro whole-blood culture with T-cell stimulants and the toll-like receptor-4 ligand lipopolysaccharide. Outcome measures were C-reactive protein, interleukin-6 (IL-6), IL-18, fibrinogen, myeloperoxidase, and a panel of 13 cytokines representative of the innate and adaptive inflammatory response, in addition to established cardiovascular markers. The in vivo acute-phase response was higher for women with previous preeclampsia than that for controls without such a history, although only significant for C-reactive protein (P=0.04). Preeclampsia was associated with higher IL-1β (P<0.05) and IL-8 (P<0.01) responses to T-cell activation. Hierarchical clustering revealed 2 distinct inflammatory clusters associated with previous preeclampsia: an adaptive response cluster associated with increased C-reactive protein and IL-6 before and after vaccination, increased weight, and low high-density lipoprotein cholesterol; and a toll-like receptor-4 mediated the cluster associated with increased IL-18 before and after vaccination but not associated with other cardiovascular markers. Furthermore, we found interactions between previous preeclampsia, common TLR4 gene variants, and the IL-18 response to vaccination. In conclusion, preeclampsia is associated with alterations in the inflammatory response postpartum mostly independent of other established cardiovascular risk markers. PMID:26711734

  10. Bimanual motor coordination controlled by cooperative interactions in intrinsic and extrinsic coordinates.

    PubMed

    Sakurada, Takeshi; Ito, Koji; Gomi, Hiroaki

    2016-01-01

    Although strong motor coordination in intrinsic muscle coordinates has frequently been reported for bimanual movements, coordination in extrinsic visual coordinates is also crucial in various bimanual tasks. To explore the bimanual coordination mechanisms in terms of the frame of reference, here we characterized implicit bilateral interactions in visuomotor tasks. Visual perturbations (finger-cursor gain change) were applied while participants performed a rhythmic tracking task with both index fingers under an in-phase or anti-phase relationship in extrinsic coordinates. When they corrected the right finger's amplitude, the left finger's amplitude unintentionally also changed [motor interference (MI)], despite the instruction to keep its amplitude constant. Notably, we observed two specificities: one was large MI and low relative-phase variability (PV) under the intrinsic in-phase condition, and the other was large MI and high PV under the extrinsic in-phase condition. Additionally, using a multiple-interaction model, we successfully decomposed MI into intrinsic components caused by motor correction and extrinsic components caused by visual-cursor mismatch of the right finger's movements. This analysis revealed that the central nervous system facilitates MI by combining intrinsic and extrinsic components in the condition with in-phases in both intrinsic and extrinsic coordinates, and that under-additivity of the effects is explained by the brain's preference for the intrinsic interaction over extrinsic interaction. In contrast, the PV was significantly correlated with the intrinsic component, suggesting that the intrinsic interaction dominantly contributed to bimanual movement stabilization. The inconsistent features of MI and PV suggest that the central nervous system regulates multiple levels of bilateral interactions for various bimanual tasks. PMID:26540267

  11. Strategies for Early Non-response to Antipsychotic Drugs in the Treatment of Acute-phase Schizophrenia

    PubMed Central

    Ito, Hiroto

    2014-01-01

    As a strategy for antipsychotic treatment of schizophrenia, monotherapy is clearly optimal when both effective and tolerated. When a patient fails to respond to an adequate dose of an antipsychotic, alternatives include switching, administering a higher dose (above the licensed dose), polypharmacy or clozapine. Clozapine is the only option with established efficacy, but is less manageable than other antipsychotics. We therefore reviewed other options, focusing on the treatment of acute-phase schizophrenia. According to recent evidence, an antipsychotic may be viewed as ineffective within 1-4 weeks in acute-phase practice, although some differences may exist among antipsychotics. Whether a switching strategy is effective might depend on the initial antipsychotic and which antipsychotic is switched to. As weak evidence points toward augmentation being superior to continuation of the initial antipsychotic, inclusion of augmentation arms in larger studies comparing strategies for early non-responders in the acute-phase is justified. With respect to high-doses, little evidence is available regarding acute-phase treatment, and the issue remains controversial. Although evidence for antipsychotic switching, augmentation, and high-doses has gradually been accumulating, more studies performed in real clinical practice with minimal bias are required to establish strategies for early non-response to an antipsychotic drug in the treatment of acute-phase schizophrenia. PMID:24851115

  12. Phase response curve for the ultradian rhythm of the lateral leaflets of Desmodium gyrans using DC current pulses.

    PubMed

    Sharma, V K; Jensen, C; Johnsson, A

    2001-01-01

    In the present study the leaf movement rhythm was perturbed by the application of DC current pulses (15 microA, 10 seconds, voltage applied: 10 V) to the upper part of the pulvinus, passing through the pulvinus and its stalk. The pulses were applied at four different positions of the leaflets: when the leaves were at the lowermost position, when moving up, at the uppermost position and when moving down. The pre-perturbed and the post-perturbed rhythms were compared. We found that the rhythms were shifted in phase and the phase shifts observed at the four different positions of the leaflets were significantly different in magnitude as well as direction. Furthermore, we could also observe phase advances, which is in contrast to an earlier finding. A phase response curve (PRC) was constructed to illustrate the sensitivity of the oscillating leaflet system to DC pulses. Substantial delays of about 50 s (as compared to the period of about 200 s) were obtained when pulses were administered at the lowermost position and when leaflet were moving upwards, while advances or no phase shifts were recorded in the uppermost position and when leaflet were moving down respectively. PMID:11302218

  13. Hepatic cytochrome P450 3A drug metabolism is reduced in cancer patients who have an acute-phase response

    PubMed Central

    Rivory, L P; Slaviero, K A; Clarke, S J

    2002-01-01

    Inflammatory disease states (infection, arthritis) are associated with reduced drug oxidation by the cytochrome P450 3A system. Many chemotherapy agents are metabolised through this pathway, and disease may therefore influence inter-individual differences in drug pharmacokinetics. The purpose of this study was to assess cytochrome P450 3A function in patients with advanced cancer, and its relation to the acute-phase response. We evaluated hepatic cytochrome P450 3A function in 40 patients with advanced cancer using the erythromycin breath test. Both the traditional C20min measure and the recently proposed 1/TMAX values were estimated. The marker of acute-phase response, C-reactive protein and the pro-inflammatory cytokines IL-6, IL-1β, TNFα and IL-8 were measured in serum or plasma at baseline. Cancer patients with an acute phase response (C-reactive protein >10 mg l−1, n=26) had reduced metabolism as measured with the erythromycin breath test 1/TMAX (Kruskal–Wallis Anova, P=0.0062) as compared to controls (C-reactive protein ⩽10 mg l−1, n=14). Indeed, metabolism was significantly associated with C-reactive protein over the whole concentration range of this acute-phase marker (r=−0.64, Spearman Rank Correlation, P<0.00001). C-reactive protein serum levels were significantly correlated with those of IL-6 (Spearman coefficient=0.58, P<0.0003). The reduction in cytochrome P450 3A function with acute-phase reaction was independent of the tumour type and C-reactive protein elevation was associated with poor performance status. This indicates that the sub-group of cancer patients with significant acute-phase response have compromised drug metabolism, which may have implications for the safety of chemotherapy in this population. British Journal of Cancer (2002) 87, 277–280. doi:10.1038/sj.bjc.6600448 www.bjcancer.com © 2002 Cancer Research UK PMID:12177794

  14. Issues in Purchasing and Maintaining Intrinsic Standards

    SciTech Connect

    PETTIT,RICHARD B.; JAEGER,KLAUS; EHRLICH,CHARLES D.

    2000-09-12

    Intrinsic standards are widely used in the metrology community because they realize the best level uncertainty for many metrology parameters. For some intrinsic standards, recommended practices have been developed to assist metrologists in the selection of equipment and the development of appropriate procedures in order to realize the intrinsic standard. As with the addition of any new standard, the metrology laboratory should consider the pros and cons relative to their needs before purchasing the standard so that the laboratory obtains the maximum benefit from setting up and maintaining these standards. While the specific issues that need to be addressed depend upon the specific intrinsic standard and the level of realization, general issues that should be considered include ensuring that the intrinsic standard is compatible with the laboratory environment, that the standard is compatible with the current and future workload, and whether additional support standards will be required in order to properly maintain the intrinsic standard. When intrinsic standards are used to realize the best level of uncertainty for a specific metrology parameter, they usually require critical and important maintenance activities. These activities can including training of staff in the system operation, as well as safety procedures; performing periodic characterization measurements to ensure proper system operation; carrying out periodic intercomparisons with similar intrinsic standards so that proper operation is demonstrated; and maintaining control or trend charts of system performance. This paper has summarized many of these important issues and therefore should be beneficial to any laboratory that is considering the purchase of an intrinsic standard.

  15. Dynamic iso-resistive trunk extension simulation: contributions of the intrinsic and reflexive mechanisms to spinal stability.

    PubMed

    Davarani, S Zeinali; Shirazi-Adl, A; Hemami, H; Mousavi, S J; Parnianpour, M

    2007-01-01

    The effects of external resistance on the recruitment of trunk muscles and the role of intrinsic and reflexive mechanisms to ensure the spinal stability are significant issues in spinal biomechanics. A computational model of spine under the control of 48 anatomically oriented muscle actions was used to simulate iso-resistive trunk movements. Neural excitation of muscles was attained based on inverse dynamics approach along with the stability-based optimization. The effect of muscle spindle reflex response on the trunk movement stability was evaluated upon the application of a perturbation moment. In this study, the trunk extension movement at various resistance levels while extending from 60 degrees flexion to the upright posture was investigated. Incorporation of the stability condition as an additional constraint in the optimization algorithm increased antagonistic activities for all resistance levels demonstrating that the co-activation caused an increase in the intrinsic stiffness of the spine and its stability in a feed-forward manner. During the acceleration phase of the movement, extensors activity increased while flexors activity decreased in response to the higher resistance. The co-activation ratio noticed in the braking phase of the movement increased with higher resistance. In presence of a 30 Nm flexion perturbation moment, reflexive feed-back noticeably decreased the induced deviation of the velocity and position profiles from the desired ones at all resistance levels. The stability-generated co-activation decreased the reflexive response of muscle spindles to the perturbation demonstrating that both intrinsic and reflexive mechanisms contribute to the trunk stability. The rise in muscle co-activation can ameliorate the corruption of afferent neural sensory system at the expense of higher loading of the spine. PMID:18057565

  16. Time course of acute-phase response induced by Tityus serrulatus venom and TsTX-I in mice.

    PubMed

    Pessini, Andréa C; de Souza, Ana M; Faccioli, Lúcia H; Gregório, Zita M O; Arantes, Eliane C

    2003-05-01

    Animal venom can induce systemic alterations similar to those observed in acute-phase inflammatory response. In the present study, we report the systemic (circulatory) and local (peritoneal cavity) effects induced by Tityus serrulatus venom and its major toxin TsTX-I (Ts1) in mice over various time periods. Both the venom and TsTX-I elicited quite similar responses in most assays. Responses included reduction of albumin, increased C-reactive protein, IL-6, IL-1alpha and TNF-alpha. Local and systemic leucocytosis, with a predominance of polymorphonuclear cells, was also observed. These effects show that a systemic inflammation-like syndrome is triggered during the severe envenomation caused by the T. serrulatus sting. The initial increases of albumin and total protein were probably consequences of the dehydration that occurs at the beginning of envenomation. Time-course analysis of these effects shows that responses are most pronounced on the first day after poisoning. However, leucocytosis and changes in acute-phase protein concentrations can be observed up to 7 days after envenomation. PMID:12757745

  17. Effects of a beetroot juice with high neobetanin content on the early-phase insulin response in healthy volunteers.

    PubMed

    Wootton-Beard, Peter C; Brandt, Kirsten; Fell, David; Warner, Sarah; Ryan, Lisa

    2014-01-01

    Produce rich in phytochemicals may alter postprandial glucose and insulin responses by interacting with the pathways that regulate glucose uptake and insulin secretion in humans. The aims of the present study were to assess the phytochemical constituents of red beetroot juice and to measure the postprandial glucose and insulin responses elicited by either 225 ml beetroot juice (BEET), a control beverage matched for macronutrient content (MCON) or a glucose beverage in healthy adults. Beetroot juice was a particularly rich source of betalain degradation compounds. The orange/yellow pigment neobetanin was measured in particularly high quantities (providing 1·3 g in the 225 ml). A total of sixteen healthy individuals were recruited, and consumed the test meals in a controlled single-blind cross-over design. Results revealed a significant lowering of the postprandial insulin response in the early phase (0-60 min) (P < 0·05) and a significantly lower glucose response in the 0-30 min phase (P < 0·05) in the BEET treatment compared with MCON. Betalains, polyphenols and dietary nitrate found in the beetroot juice may each contribute to the observed differences in the postprandial insulin concentration. PMID:25191617

  18. Study of Hind Limb Tissue Gas Phase Formation in Response to Suspended Adynamia and Hypokinesia

    NASA Technical Reports Server (NTRS)

    Butler, Bruce D.

    1996-01-01

    The purpose of this study was to investigate the hypothesis that reduced joint/muscle activity (hypo kinesia) as well as reduced or null loading of limbs (adynamia) in gravity would result in reduced decompression-induced gas phase and symptoms of decompression sickness (DCS). Finding a correlation between the two phenomena would correspond to the proposed reduction in tissue gas phase formation in astronauts undergoing decompression during extravehicular activity (EVA) in microgravity. The observation may further explain the reported low incidence of DCS in space.

  19. Machining and Phase Transformation Response of Room-Temperature Austenitic NiTi Shape Memory Alloy

    NASA Astrophysics Data System (ADS)

    Kaynak, Yusuf

    2014-09-01

    This experimental work reports the results of a study addressing tool wear, surface topography, and x-ray diffraction analysis for the finish cutting process of room-temperature austenitic NiTi alloy. Turning operation of NiTi alloy was conducted under dry, minimum quantity lubrication (MQL) and cryogenic cooling conditions at various cutting speeds. Findings revealed that cryogenic machining substantially reduced tool wear and improved surface topography and quality of the finished parts in comparison with the other two approaches. Phase transformation on the surface of work material was not observed after dry and MQL machining, but B19' martensite phase was found on the surface of cryogenically machined samples.

  20. Human phase response curve to a single 6.5 h pulse of short-wavelength light

    PubMed Central

    Rüger, Melanie; St Hilaire, Melissa A; Brainard, George C; Khalsa, Sat-Bir S; Kronauer, Richard E; Czeisler, Charles A; Lockley, Steven W

    2013-01-01

    The photic resetting response of the human circadian pacemaker depends on the timing of exposure, and the direction and magnitude of the resulting shift is described by a phase response curve (PRC). Previous PRCs in humans have utilized high-intensity polychromatic white light. Given that the circadian photoreception system is maximally sensitive to short-wavelength visible light, the aim of the current study was to construct a PRC to blue (480 nm) light and compare it to a 10,000 lux white light PRC constructed previously using a similar protocol. Eighteen young healthy participants (18–30 years) were studied for 9–10 days in a time-free environment. The protocol included three baseline days followed by a constant routine (CR) to assess initial circadian phase. Following this CR, participants were exposed to a 6.5 h 480 nm light exposure (11.8 μW cm−2, 11.2 lux) following mydriasis via a modified Ganzfeld dome. A second CR was conducted following the light exposure to re-assess circadian phase. Phase shifts were calculated from the difference in dim light melatonin onset (DLMO) between CRs. Exposure to 6.5 h of 480 nm light resets the circadian pacemaker according to a conventional type 1 PRC with fitted maximum delays and advances of −2.6 h and 1.3 h, respectively. The 480 nm PRC induced ∼75% of the response of the 10,000 lux white light PRC. These results may contribute to a re-evaluation of dosing guidelines for clinical light therapy and the use of light as a fatigue countermeasure. PMID:23090946

  1. Response of Global Lightning Activity Observed by the TRMM/LIS During Warm and Cold ENSO Phases

    NASA Technical Reports Server (NTRS)

    Chronis, Themis G.; Cecil, Dan; Goodman, Steven J.; Buechler, Dennis

    2007-01-01

    This paper investigates the response of global lightning activity to the transition from the warm (January February March-JFM 1998) to the cold (JFM 1999) ENSO phase. The nine-year global lightning climatology for these months from the Tropical Rainfall Measuring Mission (TRMM) Lightning Imaging Sensor (LIS) provides the observational baseline. Flash rate density is computed on a 5.0x5.0 degree lat/lon grid within the LIS coverage area (between approx.37.5 N and S) for each three month period. The flash rate density anomalies from this climatology are examined for these months in 1998 and 1999. The observed lightning anomalies spatially match the documented general circulation features that accompany the warm and cold ENSO events. During the warm ENSO phase the dominant positive lightning anomalies are located mostly over the Western Hemisphere and more specifically over Gulf of Mexico, Caribbean and Northern Mid-Atlantic. We further investigate specifically the Northern Mid-Atlantic related anomaly features since these show strong relation to the North Atlantic Oscillation (NAO). Furthermore these observed anomaly patterns show strong spatial agreement with anomalous upper level (200 mb) cold core cyclonic circulations. Positive sea surface temperature anomalies during the warm ENSO phase also affect the lightning activity, but this is mostly observed near coastal environments. Over the open tropical oceans, there is climatologically less lightning and the anomalies are less pronounced. Warm ENSO related anomalies over the Eastern Hemisphere are most prominent over the South China coast. The transition to the cold ENSO phase illustrates the detected lightning anomalies to be more pronounced over East and West Pacific. A comparison of total global lightning between warm and cold ENSO phase reveals no significant difference, although prominent regional anomalies are located over mostly oceanic environments. All three tropical "chimneys" (Maritime Continent, Central

  2. Intrinsic ductility of glassy solids

    NASA Astrophysics Data System (ADS)

    Shi, Yunfeng; Luo, Jian; Yuan, Fenglin; Huang, Liping

    2014-01-01

    Glasses are usually brittle, seriously limiting their practical usage. Recently, the intrinsic ductility of glass was found to increase with the Poisson's ratio (v), with a sharp brittle-to-ductile (BTD) transition at vBTD = 0.31-0.32. Such a correlation between far-from-equilibrium fracture and near-equilibrium elasticity is unexpected and not understood. Molecular dynamics simulations, on three families of glasses (metallic glasses, amorphous silicon, and silica) with controlled bonding, processing, and testing conditions, show that glasses with low covalency and high structural disorder have high v and ductility, and vice versa. The BTD transitions triggered by the aforementioned causes in each system correspond to a unified vBTD value, which increases with its average coordination number (CN). The vBTD-CN relation can be comprehended by recognizing v as a measure of covalency and disorder, and the BTD transition as a competition between shear and cleavage. Our results provide guidelines for developing new recipes and processes for tough glasses.

  3. Intrinsic Localized Modes in Proteins

    PubMed Central

    Nicolaï, Adrien; Delarue, Patrice; Senet, Patrick

    2015-01-01

    Protein dynamics is essential for proteins to function. Here we predicted the existence of rare, large nonlinear excitations, termed intrinsic localized modes (ILMs), of the main chain of proteins based on all-atom molecular dynamics simulations of two fast-folder proteins and of a rigid α/β protein at 300 K and at 380 K in solution. These nonlinear excitations arise from the anharmonicity of the protein dynamics. The ILMs were detected by computing the Shannon entropy of the protein main-chain fluctuations. In the non-native state (significantly explored at 380 K), the probability of their excitation was increased by a factor between 9 and 28 for the fast-folder proteins and by a factor 2 for the rigid protein. This enhancement in the non-native state was due to glycine, as demonstrated by simulations in which glycine was mutated to alanine. These ILMs might play a functional role in the flexible regions of proteins and in proteins in a non-native state (i.e. misfolded or unfolded states). PMID:26658321

  4. Intrinsic Localized Modes in Proteins.

    PubMed

    Nicolaï, Adrien; Delarue, Patrice; Senet, Patrick

    2015-01-01

    Protein dynamics is essential for proteins to function. Here we predicted the existence of rare, large nonlinear excitations, termed intrinsic localized modes (ILMs), of the main chain of proteins based on all-atom molecular dynamics simulations of two fast-folder proteins and of a rigid α/β protein at 300 K and at 380 K in solution. These nonlinear excitations arise from the anharmonicity of the protein dynamics. The ILMs were detected by computing the Shannon entropy of the protein main-chain fluctuations. In the non-native state (significantly explored at 380 K), the probability of their excitation was increased by a factor between 9 and 28 for the fast-folder proteins and by a factor 2 for the rigid protein. This enhancement in the non-native state was due to glycine, as demonstrated by simulations in which glycine was mutated to alanine. These ILMs might play a functional role in the flexible regions of proteins and in proteins in a non-native state (i.e. misfolded or unfolded states). PMID:26658321

  5. Intrinsically photosensitive retinal ganglion cells.

    PubMed

    Do, Michael Tri Hoang; Yau, King-Wai

    2010-10-01

    Life on earth is subject to alternating cycles of day and night imposed by the rotation of the earth. Consequently, living things have evolved photodetective systems to synchronize their physiology and behavior with the external light-dark cycle. This form of photodetection is unlike the familiar "image vision," in that the basic information is light or darkness over time, independent of spatial patterns. "Nonimage" vision is probably far more ancient than image vision and is widespread in living species. For mammals, it has long been assumed that the photoreceptors for nonimage vision are also the textbook rods and cones. However, recent years have witnessed the discovery of a small population of retinal ganglion cells in the mammalian eye that express a unique visual pigment called melanopsin. These ganglion cells are intrinsically photosensitive and drive a variety of nonimage visual functions. In addition to being photoreceptors themselves, they also constitute the major conduit for rod and cone signals to the brain for nonimage visual functions such as circadian photoentrainment and the pupillary light reflex. Here we review what is known about these novel mammalian photoreceptors. PMID:20959623

  6. Growth Phase-Dependent Response of Helicobacter pylori to Iron Starvation

    PubMed Central

    Merrell, D. Scott; Thompson, Lucinda J.; Kim, Charles C.; Mitchell, Hazel; Tompkins, Lucy S.; Lee, Adrian; Falkow, Stanley

    2003-01-01

    Iron is an essential nutrient that is often found in extremely limited available quantities within eukaryotic hosts. Because of this, many pathogenic bacteria have developed regulated networks of genes important for iron uptake and storage. In addition, it has been shown that many bacteria use available iron concentrations as a signal to regulate virulence gene expression. We have utilized DNA microarray technology to identify genes of the human pathogen Helicobacter pylori that are differentially regulated on a growth-inhibiting shift to iron starvation conditions. In addition, the growth phase-dependent expression of these genes was investigated by examining both exponential and stationary growth phase cultures. We identified known iron-regulated genes, as well as a number of genes whose regulation by iron concentration was not previously appreciated. Included in the list of regulated factors were the known virulence genes cagA, vacA, and napA. We examined the effect of iron starvation on the motility of H. pylori and found that exponential- and stationary-phase cultures responded differently to the stress. We further found that while growing cells are rapidly killed by iron starvation, stationary-phase cells show a remarkable ability to survive iron depletion. Finally, bioinformatic analysis of the predicted promoter regions of the differentially regulated genes led to identification of several putative Fur boxes, suggesting a direct role for Fur in iron-dependent regulation of these genes. PMID:14573673

  7. Early weaning alters the acute phase response to an endotoxin challenge in beef calves

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous research indicates that early weaning prior to shipment can reduce transportation-induced increases in acute phase proteins (APP), and can increase subsequent performance in the feedlot. These data suggest that the combination of weaning and transport stress may compromise the immune system...

  8. Intrinsic structural defects in monolayer molybdenum disulfide

    SciTech Connect

    Zhou, Wu; Idrobo Tapia, Juan C

    2013-01-01

    Monolayer molybdenum disulfide (MoS2) is a two-dimensional direct band gap semiconductor with distinctive mechanical, electronic, optical and chemical properties that can be utilized for novel nanoelectronics and optoelectronics devices. The performance of these electronic devices strongly depends on the quality and defect morphology of the MoS2 layers. Yet, little is known about the atomic structure of defects present in monolayer MoS2 and their influences on the material properties. Here we provide a systematic study of various intrinsic structural defects, including point defects, grain boundaries, and edges, in chemical vapor phase grown monolayer MoS2 via direct atomic resolution imaging, and explore their energy landscape and electronic properties using first-principles calculations. We discover that one-dimensional metallic wires can be created via two different types of 60 grain boundaries consisting of distinct 4-fold ring chains. A new type of edge reconstruction, representing a transition state during growth, was also identified, providing insights into the material growth mechanism. The atomic scale study of structural defects presented here brings new opportunities to tailor the properties of MoS2 via controlled synthesis and defect engineering.

  9. Intrinsic vs. extrinsic controls on channel evolution in a sub-tropical river, Australia

    NASA Astrophysics Data System (ADS)

    Daley, James; Croke, Jacky; Thompson, Chris; Cohen, Tim; Macklin, Mark; Sharma, Ashneel

    2016-04-01

    Palaeohydrological research provides valuable insights to the understanding of short- and long-term fluvial dynamics in response to climate change and tectonic activity. In landscapes where tectonic activity is minimal fluvial archives record long-term changes in sediment and discharge dynamics related to either intrinsic or extrinsic controls. Isolating the relative controls of these factors is an important frontier in this area of research. Advances in geochronology, the acquisition of high resolution topographic data and geomorphological techniques provide an opportunity to assess the relative importance of intrinsic and extrinsic controls on terrace and floodplain formation. This study presents the results of detailed chrono-stratigraphic research in a partly confined river valley in subtropical southeast Queensland. River systems within this region are characterized by high hydrological variability and have a near-ubiquitous compound channel morphology (macrochannel) where Holocene deposits are inset within late Pleistocene terraces. These macrochannels can accommodate floods up to and beyond the predicted 100-year flood. Using single grain optically stimulated luminescence and radiocarbon analyses, combined with high resolution spatial datasets, we demonstrate the nature of fluvial response to major late Quaternary climate change. A large proportion of the valley floor is dominated by terrace alluvium deposited after the Last Glacial Maximum (LGM) (17 - 13 ka) and overlies basal older Pleistocene alluvium. Preliminary results suggest a phase of incision occurred at 10 ka with the formation of the large alluvial trench. The Holocene floodplain is dominated by processes of catastrophic vertical accretion and erosion (cut-and-fill) and oblique accretion at the macrochannel margins. The consistency in ages for the terraces and subsequent incision suggests a uniform network response. Alluvial sediments and channel configuration in this compound and complex

  10. Distinct molecular signatures of mild extrinsic and intrinsic atopic dermatitis.

    PubMed

    Martel, Britta C; Litman, Thomas; Hald, Andreas; Norsgaard, Hanne; Lovato, Paola; Dyring-Andersen, Beatrice; Skov, Lone; Thestrup-Pedersen, Kristian; Skov, Søren; Skak, Kresten; Poulsen, Lars K

    2016-06-01

    Atopic dermatitis (AD) is a common inflammatory skin disease with underlying defects in epidermal function and immune responses. In this study, we used microarray analysis to investigate differences in gene expression in lesional skin from patients with mild extrinsic or intrinsic AD compared to skin from healthy controls and from lesional psoriasis skin. The primary aim was to identify differentially expressed genes involved in skin barrier formation and inflammation, and to compare our results with those reported for patients with moderate and severe AD. In contrast to severe AD, expression of the majority of genes associated with skin barrier formation was unchanged or upregulated in patients with mild AD compared to normal healthy skin. Among these, no significant differences in the expression of filaggrin (FLG) and loricrin at both mRNA and protein level were found in lesional skin from patients with mild AD, despite the presence of heterozygous FLG mutations in the majority of patients with mild extrinsic AD. Several inflammation-associated genes such as S100A9, MMP12, CXCL10 and CCL18 were highly expressed in lesional skin from patients with mild psoriasis and were also increased in patients with mild extrinsic and intrinsic AD similar to previous reports for severe AD. Interestingly, expression of genes involved in inflammatory responses in intrinsic AD resembled that of psoriasis more than that of extrinsic AD. Overall, differences in expression of inflammation-associated genes found among patients with mild intrinsic and extrinsic AD correlated with previous findings for patients with severe intrinsic and extrinsic AD. PMID:26841714

  11. Unusual Electro-Optic Kerr Response in a Self-Stabilized Amorphous Blue Phase with Nanoscale Smectic Clusters.

    PubMed

    Le, Khoa V; Hafuri, Miho; Ocak, Hale; Bilgin-Eran, Belkız; Tschierske, Carsten; Sasaki, Takeo; Araoka, Fumito

    2016-05-18

    We investigated the electro-optic response in the "foggy" amorphous blue phase (BPIII) as well as in the isotropic phase. To the best of our knowledge, such a study has not yet been performed due to the very limited thermal range of BPIII. In this study, we used a single-component chiral bent-core liquid crystal with a self-stabilized BPIII, which is stable over a wide temperature range. The results show that the response time is on the order of hundreds of microseconds in the isotropic phase and increases to 1-2 ms in the BPIII (at TI-BP -T <1), then drastically increases up to a few tens of milliseconds upon further cooling in BPIII. Such an unusual behavior was explained on the basis of the high rotational viscosity and/or the existence of nanoscale smectic (Sm) clusters. The Kerr constant was also measured and found to be ∼500 pm V(-2) , which is the largest among bent-core BP systems reported so far and comparable with that of polymer-stabilized BPs. PMID:26910727

  12. Similarities in acute phase protein response during hibernation in black bears and major depression in humans: A response to underlying metabolic depression?

    USGS Publications Warehouse

    Tsiouris, J.A.; Chauhan, V.P.S.; Sheikh, A.M.; Chauhan, A.; Malik, M.; Vaughan, M.R.

    2004-01-01

    This study investigated the effects of hibernation with mild hypothermia and the stress of captivity on levels of six acute-phase proteins (APPs) in serial samples of serum from 11 wild and 6 captive black bears (Ursus americanus Pallas, 1780) during active and hibernating states. We hypothesize that during hibernation with mild hypothermia, bears would show an APP response similar to that observed in major depression. Enzyme-linked immunoabsorbent assay was used to measure alpha2-macroglobulin and C-reactive protein, and a nephelometer to measure alpha1-antitrypsin, haptoglobin, ceruloplasmin, and transferrin. Levels of all other proteins except ceruloplasmin were significantly elevated during hibernation in both wild and captive bears at the p < 0.05 to p < 0.001 level. Alpha 2-macroglobulin and C-reactive-protein levels were increased in captive versus wild bears in both active and hibernating states at the p < 0.01 to p < 0.0001 level. During hibernation with mild hypothermia, black bears do not show immunosuppression, but show an increased APP response similar to that in patients with major depression. This APP response is explained as an adaptive response to the underlying metabolic depression in both conditions. Metabolic depression in hibernating bears is suggested as a natural model for research to explain the neurobiology of depression.

  13. Intrinsic bioremediation of landfills interim report

    SciTech Connect

    Brigmon, R.L.; Fliermans, C.B.

    1997-07-14

    Intrinsic bioremediation is a risk management option that relies on natural biological and physical processes to contain the spread of contamination from a source. Evidence is presented in this report that intrinsic bioremediation is occurring at the Sanitary Landfill is fundamental to support incorportion into a Corrective Action Plan (CAP).

  14. Modelling the response of a vibrating-element density meter in a two-phase mixture

    NASA Astrophysics Data System (ADS)

    Billingham, John

    1997-06-01

    A vibrating-element density meter is a mechanical oscillator with known properties, for example a tuning fork or a simple rod, driven to vibrate at a known frequency. The oscillator is immersed in a fluid and the resonant frequency measured. The density of the fluid can then be inferred. We consider an idealized meter immersed in two-phase flows of various types, and investigate whether a simple single-phase interpretation allows us to deduce the density of the mixture. We find that, when the density contrast between the two fluids is not great, the simple interpretation gives good results, for example in oil/water flows. However, when the density contrast is significant, for example in gas/liquid flows, the simple interpretation is highly inaccurate.

  15. Phase behavior and unusual dynamics of stimuli-responsive microgel colloids

    NASA Astrophysics Data System (ADS)

    Tata, B. V. R.

    2013-02-01

    Monodisperse poly (N-isopropylacrylamide) (PNIPAM) microgel particles in aqueous medium exhibit structural ordering similar to that observed in atomic systems. Colloidal crystals of these microgel particles exhibit series of phase transitions with increase in temperature due to reduction in the particle size and variation in the interparticle interactions. Unlike hard-sphere or charged colloidal particles, microgel particles are heterogeneous in particle density with dense solvent penetrable polymer core and brush-like polymer chains forming a shell. In this talk I will present static/dynamic light scattering, confocal microscopy and UV-Visible spectroscopy results on dense microgel suspensions exhibiting unusual dynamics across melting, tunabilty of Bragg diffraction, particle distribution and nature of interparticle interaction upon osmotic compression. From these results I conclude that PNIPAM microgel sphere are not only soft but also compressible and differ from other hard-sphere and charged colloidal systems in significant way in their structure, dynamics and phase behaviour.

  16. Shock Response and Phase Transitions of MgO at Planetary Impact Conditions

    NASA Astrophysics Data System (ADS)

    Root, Seth; Shulenburger, Luke; Lemke, Raymond W.; Dolan, Daniel H.; Mattsson, Thomas R.; Desjarlais, Michael P.

    2015-11-01

    The moon-forming impact and the subsequent evolution of the proto-Earth is strongly dependent on the properties of materials at the extreme conditions generated by this violent collision. We examine the high pressure behavior of MgO, one of the dominant constituents in Earth's mantle, using high-precision, plate impact shock compression experiments performed on Sandia National Laboratories' Z Machine and extensive quantum calculations using density functional theory (DFT) and quantum Monte Carlo (QMC) methods. The combined data span from ambient conditions to 1.2 TPa and 42 000 K, showing solid-solid and solid-liquid phase boundaries. Furthermore our results indicate that under impact the solid and liquid phases coexist for more than 100 GPa, pushing complete melting to pressures in excess of 600 GPa. The high pressure required for complete shock melting has implications for a broad range of planetary collision events.

  17. Shock response and phase transitions of MgO at planetary impact conditions

    DOE PAGESBeta

    Root, Seth; Shulenburger, Luke; Lemke, Raymond W.; Dolan, Daniel H.; Mattsson, Thomas R.; Desjarlais, Michael P.

    2015-11-04

    The moon-forming impact and the subsequent evolution of the proto-Earth is strongly dependent on the properties of materials at the extreme conditions generated by this violent collision. We examine the high pressure behavior of MgO, one of the dominant constituents in Earth’s mantle, using high-precision, plate impact shock compression experiments performed on Sandia National Laboratories’ Z Machine and extensive quantum calculations using density functional theory (DFT) and quantum Monte Carlo (QMC) methods. The combined data span from ambient conditions to 1.2 TPa and 42,000 K, showing solid-solid and solid-liquid phase boundaries. Furthermore our results indicate that under impact the solidmore » and liquid phases coexist for more than 100 GPa, pushing complete melting to pressures in excess of 600 GPa. Furthermore, the high pressure required for complete shock melting has implications for a broad range of planetary collision events.« less

  18. Shock response and phase transitions of MgO at planetary impact conditions

    SciTech Connect

    Root, Seth; Shulenburger, Luke; Lemke, Raymond W.; Dolan, Daniel H.; Mattsson, Thomas R.; Desjarlais, Michael P.

    2015-11-04

    The moon-forming impact and the subsequent evolution of the proto-Earth is strongly dependent on the properties of materials at the extreme conditions generated by this violent collision. We examine the high pressure behavior of MgO, one of the dominant constituents in Earth’s mantle, using high-precision, plate impact shock compression experiments performed on Sandia National Laboratories’ Z Machine and extensive quantum calculations using density functional theory (DFT) and quantum Monte Carlo (QMC) methods. The combined data span from ambient conditions to 1.2 TPa and 42,000 K, showing solid-solid and solid-liquid phase boundaries. Furthermore our results indicate that under impact the solid and liquid phases coexist for more than 100 GPa, pushing complete melting to pressures in excess of 600 GPa. Furthermore, the high pressure required for complete shock melting has implications for a broad range of planetary collision events.

  19. Phase-dependent justification: the role of personal responsibility in fair healthcare.

    PubMed

    Bærøe, Kristine; Cappelen, Cornelius

    2015-10-01

    The main aim of this paper is to examine the fairness of different ways of holding people responsible for healthcare-related choices. Our focus is on conceptualisations of responsibility that involve blame and sanctions, and our analytical approach is to provide a systematic discussion based on interrelated and successive health-related, lifestyle choices of an individual. We assess the already established risk-sharing, backward-looking and forward-looking views on responsibility according to a variety of standard objections. In conclusion, all of the proposed views on holding people responsible for their lifestyle choices are subjected to reasonable critiques, although the risk-sharing view fare considerably better than the others overall considered. With our analytical approach, we are able to identify how basic conditions for responsibility ascription alter along a time axis. Repeated relapses with respect to healthcare associated with persistent, unhealthy lifestyle choices, call for distinct attention. In such situations, contextualised reasoning and transparent policy-making, rather than opaque clinical judgements, are required as steps towards fair allocation of healthcare resources. PMID:26269464

  20. An investigation of wing buffeting response at subsonic and transonic speeds. Phase 2: F-111A flight data analysis. Volume 1: Summary of technical approach, results and conclusions

    NASA Technical Reports Server (NTRS)

    Benepe, D. B.; Cunningham, A. M., Jr.; Traylor, S., Jr.; Dunmyer, W. D.

    1978-01-01

    A detailed investigation of the flight buffeting response of the F-111A was performed in two phases. In Phase 1 stochastic analysis techniques were applied to wing and fuselage responses for maneuvers flown at subsonic speeds and wing leading edge sweep of 26 degrees. Power spectra and rms values were obtained. This report gives results of Phase 2 where the analyses were extended to include maneuvers flown at wing leading edge sweep values of 50 and 75.5 degrees at subsonic and supersonic speeds and the responses examined were expanded to include vertical shear, bending moment, and hingeline torque of the left and right horizontal tails. Power spectra, response time histories, variations of rms response with angle of attack and effects of wing sweep and Mach number are presented and discussed. Some Phase 1 results are given for comparison purposes.

  1. Small-angle neutron and X-ray scattering from amphiphilic stimuli-responsive diamond-type bicontinuous cubic phase.

    PubMed

    Angelov, Borislav; Angelova, Angelina; Garamus, Vasil M; Lebas, Geneviève; Lesieur, Sylviane; Ollivon, Michel; Funari, Sérgio S; Willumeit, Regine; Couvreur, Patrick

    2007-11-01

    The structural evolution of a diamond-type bicontinuous lipid cubic phase upon application of thermal and chemical (hydration agent) stimuli is investigated by means of small-angle neutron (SANS) and X-ray scattering (SAXS). The soft-matter cubic architecture responds by dramatic swelling (DLarge cubic structure) upon incorporation of a hydration-enhancing guest component (octyl glucoside) at low and ambient temperatures, the aqueous channel diameter increasing twice to approximately 7 nm. DLarge appears to be built up from an assembly of cubosomic domains, which may coexist with an amphiphilic lamellae domain at low temperatures. The chemical stimulus concentration can be selected as to tune the hydration of the nanochannels in the DLarge phase and its transformation into a DNormal phase at temperatures above the body temperature. Two-dimensional SANS images recorded upon heating scan reveal growth of spontaneously oriented domains of single-crystal cubic nature. Phase separation and squeezing out the guest-hydrating agent from the higher-curvature regions of the amphiphilic bilayer suggest a possible mechanism for the established transformations. The order-order structural transition, cubic DLarge-cubic DNormal, is found to be reversible upon cooling. The obtained results put forward a structure-based concept for release of encapsulated guest molecules from stimuli-responsive and self-regulated cubosomic nanocarriers. PMID:17929809

  2. Comparison of gamma-gamma Phase Coarsening Responses of Three Powder Metal Disk Superalloys

    NASA Technical Reports Server (NTRS)

    Gabb, T. P.; Gayda, J.; Johnson, D. F.; MacKay, R. A.; Rogers, R. B.; Sudbrack, C. K.; Garg, A.; Locci, I. E.; Semiatin, S. L.; Kang, E.

    2016-01-01

    The phase microstructures of several powder metal (PM) disk superalloys were quantitatively evaluated. Contents, chemistries, and lattice parameters of gamma and gamma strengthening phase were determined for conventionally heat treated Alloy 10, LSHR, and ME3 superalloys, after electrolytic phase extractions. Several of long term heat treatments were then performed, to allow quantification of the precipitation, content, and size distribution of gamma at a long time interval to approximate equilibrium conditions. Additional coarsening heat treatments were performed at multiple temperatures and shorter time intervals, to allow quantification of the precipitation, contents and size distributions of gamma at conditions diverging from equilibrium. Modest differences in gamma and gamma lattice parameters and their mismatch were observed among the alloys, which varied with heat treatment. Yet, gamma coarsening rates were very similar for all three alloys in the heat treatment conditions examined. Alloy 10 had higher gamma dissolution and formation temperatures than LSHR and ME3, but a lower lattice mismatch, which was slightly positive for all three alloys at room temperature. The gamma precipitates of Alloy 10 appeared to remain coherent at higher temperatures than for LSHR and ME3. Higher coarsening rates were observed for gamma precipitates residing along grain boundaries than for those within grains in all three alloys, during slow-moderate quenching from supersolvus solution heat treatments, and during aging at temperatures of 843 C and higher.

  3. Mathematical model reveals how regulating the three phases of T-cell response could counteract immune evasion.

    PubMed

    Lorenzi, Tommaso; Chisholm, Rebecca H; Melensi, Matteo; Lorz, Alexander; Delitala, Marcello

    2015-10-01

    T cells are key players in immune action against the invasion of target cells expressing non-self antigens. During an immune response, antigen-specific T cells dynamically sculpt the antigenic distribution of target cells, and target cells concurrently shape the host's repertoire of antigen-specific T cells. The succession of these reciprocal selective sweeps can result in 'chase-and-escape' dynamics and lead to immune evasion. It has been proposed that immune evasion can be countered by immunotherapy strategies aimed at regulating the three phases of the immune response orchestrated by antigen-specific T cells: expansion, contraction and memory. Here, we test this hypothesis with a mathematical model that considers the immune response as a selection contest between T cells and target cells. The outcomes of our model suggest that shortening the duration of the contraction phase and stabilizing as many T cells as possible inside the long-lived memory reservoir, using dual immunotherapies based on the cytokines interleukin-7 and/or interleukin-15 in combination with molecular factors that can keep the immunomodulatory action of these interleukins under control, should be an important focus of future immunotherapy research. PMID:26119966

  4. Separating Scattering from Intrinsic Attenuation

    NASA Astrophysics Data System (ADS)

    van Wijk, K.; Scales, J. A.

    2003-12-01

    The subsurface appears disordered at all length-scales. Therefore, wave propatation at seismic or ultrasonic frequencies is subject to complicated scatterings. A pulse propagating in the subsurface loses energy at each scattering off an impedance contrast, but also decreases in amplitude as the impulse interacts with fluids in the rock. We call the latter non-elastic effect "intrinsic Q", while the former is "scattering Q". It is often the fluids in the rocks that are of interest, but conventional reflection and transmission of the incident pulse only cannot deceipher the individual components of Q due to scattering and fluid movement in the pore-space. We present an approach that can unravel these two mechanisms, allowing a separate estimate of absorption. This method treats the propagation of the average intensity in the framework of radiative transfer (RT); the arrival of (what is left of) the incident pulse is modeled as the coherent energy, whereas the later arriving multiply scattered events form the incoherent intensity. The coherent pulse decays exponentially due to a combination of scattering and absorption, and so does the incoherent intensity. However, multiple scattering can re-direct energy back to the receiver, supplying a gain-term at later times that makes up the incoherent intensity. Strictly speaking, one can invert for scattering and absorption from the intensity at late times only, often modeled with the late-time equivalent of RT, diffusion. However, we will show that fitting both early- and late-time signal with RT constrains absorption and scattering constants more rigorously. These ideas are illustrated by laboratory and sonic-logging measurements.

  5. The restless brain: how intrinsic activity organizes brain function.

    PubMed

    Raichle, Marcus E

    2015-05-19

    Traditionally studies of brain function have focused on task-evoked responses. By their very nature such experiments tacitly encourage a reflexive view of brain function. While such an approach has been remarkably productive at all levels of neuroscience, it ignores the alternative possibility that brain functions are mainly intrinsic and ongoing, involving information processing for interpreting, responding to and predicting environmental demands. I suggest that the latter view best captures the essence of brain function, a position that accords well with the allocation of the brain's energy resources, its limited access to sensory information and a dynamic, intrinsic functional organization. The nature of this intrinsic activity, which exhibits a surprising level of organization with dimensions of both space and time, is revealed in the ongoing activity of the brain and its metabolism. As we look to the future, understanding the nature of this intrinsic activity will require integrating knowledge from cognitive and systems neuroscience with cellular and molecular neuroscience where ion channels, receptors, components of signal transduction and metabolic pathways are all in a constant state of flux. The reward for doing so will be a much better understanding of human behaviour in health and disease. PMID:25823869

  6. The restless brain: how intrinsic activity organizes brain function

    PubMed Central

    Raichle, Marcus E.

    2015-01-01

    Traditionally studies of brain function have focused on task-evoked responses. By their very nature such experiments tacitly encourage a reflexive view of brain function. While such an approach has been remarkably productive at all levels of neuroscience, it ignores the alternative possibility that brain functions are mainly intrinsic and ongoing, involving information processing for interpreting, responding to and predicting environmental demands. I suggest that the latter view best captures the essence of brain function, a position that accords well with the allocation of the brain's energy resources, its limited access to sensory information and a dynamic, intrinsic functional organization. The nature of this intrinsic activity, which exhibits a surprising level of organization with dimensions of both space and time, is revealed in the ongoing activity of the brain and its metabolism. As we look to the future, understanding the nature of this intrinsic activity will require integrating knowledge from cognitive and systems neuroscience with cellular and molecular neuroscience where ion channels, receptors, components of signal transduction and metabolic pathways are all in a constant state of flux. The reward for doing so will be a much better understanding of human behaviour in health and disease. PMID:25823869

  7. Activation of InsP3 receptors is sufficient for inducing graded intrinsic plasticity in rat hippocampal pyramidal neurons

    PubMed Central

    Ashhad, Sufyan; Johnston, Daniel

    2014-01-01

    The synaptic plasticity literature has focused on establishing necessity and sufficiency as two essential and distinct features in causally relating a signaling molecule to plasticity induction, an approach that has been surprisingly lacking in the intrinsic plasticity literature. In this study, we complemented the recently established necessity of inositol trisphosphate (InsP3) receptors (InsP3R) in a form of intrinsic plasticity by asking if InsP3R activation was sufficient to induce intrinsic plasticity in hippocampal neurons. Specifically, incorporation of d-myo-InsP3 in the recording pipette reduced input resistance, maximal impedance amplitude, and temporal summation but increased resonance frequency, resonance strength, sag ratio, and impedance phase lead. Strikingly, the magnitude of plasticity in a