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Sample records for positive feedback mechanisms

  1. Amplification of ABA biosynthesis and signaling through a positive feedback mechanism in seeds.

    PubMed

    Nonogaki, Mariko; Sall, Khadidiatou; Nambara, Eiji; Nonogaki, Hiroyuki

    2014-05-01

    Abscisic acid is an essential hormone for seed dormancy. Our previous study using the plant gene switch system, a chemically induced gene expression system, demonstrated that induction of 9-cis-epoxycarotenoid dioxygenase (NCED), a rate-limiting ABA biosynthesis gene, was sufficient to suppress germination in imbibed Arabidopsis seeds. Here, we report development of an efficient experimental system that causes amplification of NCED expression during seed maturation. The system was created with a Triticum aestivum promoter containing ABA responsive elements (ABREs) and a Sorghum bicolor NCED to cause ABA-stimulated ABA biosynthesis and signaling, through a positive feedback mechanism. The chimeric gene pABRE:NCED enhanced NCED and ABF (ABRE-binding factor) expression in Arabidopsis Columbia-0 seeds, which caused 9- to 73-fold increases in ABA levels. The pABRE:NCED seeds exhibited unusually deep dormancy which lasted for more than 3 months. Interestingly, the amplified ABA pathways also caused enhanced expression of Arabidopsis NCED5, revealing the presence of positive feedback in the native system. These results demonstrated the robustness of positive feedback mechanisms and the significance of NCED expression, or single metabolic change, during seed maturation. The pABRE:NCED system provides an excellent experimental system producing dormant and non-dormant seeds of the same maternal origin, which differ only in zygotic ABA. The pABRE:NCED seeds contain a GFP marker which enables seed sorting between transgenic and null segregants and are ideal for comparative analysis. In addition to its utility in basic research, the system can also be applied to prevention of pre-harvest sprouting during crop production, and therefore contributes to translational biology. PMID:24520869

  2. Position feedback control system

    DOEpatents

    Bieg, Lothar F.; Jokiel, Jr., Bernhard; Ensz, Mark T.; Watson, Robert D.

    2003-01-01

    Disclosed is a system and method for independently evaluating the spatial positional performance of a machine having a movable member, comprising an articulated coordinate measuring machine comprising: a first revolute joint; a probe arm, having a proximal end rigidly attached to the first joint, and having a distal end with a probe tip attached thereto, wherein the probe tip is pivotally mounted to the movable machine member; a second revolute joint; a first support arm serially connecting the first joint to the second joint; and coordinate processing means, operatively connected to the first and second revolute joints, for calculating the spatial coordinates of the probe tip; means for kinematically constraining the articulated coordinate measuring machine to a working surface; and comparator means, in operative association with the coordinate processing means and with the movable machine, for comparing the true position of the movable machine member, as measured by the true position of the probe tip, with the desired position of the movable machine member.

  3. Depletion of retinoic acid receptors initiates a novel positive feedback mechanism that promotes teratogenic increases in retinoic acid.

    PubMed

    D'Aniello, Enrico; Rydeen, Ariel B; Anderson, Jane L; Mandal, Amrita; Waxman, Joshua S

    2013-01-01

    Normal embryonic development and tissue homeostasis require precise levels of retinoic acid (RA) signaling. Despite the importance of appropriate embryonic RA signaling levels, the mechanisms underlying congenital defects due to perturbations of RA signaling are not completely understood. Here, we report that zebrafish embryos deficient for RA receptor αb1 (RARαb1), a conserved RAR splice variant, have enlarged hearts with increased cardiomyocyte (CM) specification, which are surprisingly the consequence of increased RA signaling. Importantly, depletion of RARαb2 or concurrent depletion of RARαb1 and RARαb2 also results in increased RA signaling, suggesting this effect is a broader consequence of RAR depletion. Concurrent depletion of RARαb1 and Cyp26a1, an enzyme that facilitates degradation of RA, and employment of a novel transgenic RA sensor line support the hypothesis that the increases in RA signaling in RAR deficient embryos are the result of increased embryonic RA coupled with compensatory RAR expression. Our results support an intriguing novel mechanism by which depletion of RARs elicits a previously unrecognized positive feedback loop that can result in developmental defects due to teratogenic increases in embryonic RA. PMID:23990796

  4. Histone demethylase KDM5A is regulated by its reader domain through a positive-feedback mechanism

    NASA Astrophysics Data System (ADS)

    Torres, Idelisse Ortiz; Kuchenbecker, Kristopher M.; Nnadi, Chimno I.; Fletterick, Robert J.; Kelly, Mark J. S.; Fujimori, Danica Galonić

    2015-02-01

    The retinoblastoma binding protein KDM5A removes methyl marks from lysine 4 of histone H3 (H3K4). Misregulation of KDM5A contributes to the pathogenesis of lung and gastric cancers. In addition to its catalytic jumonji C domain, KDM5A contains three PHD reader domains, commonly recognized as chromatin recruitment modules. It is unknown whether any of these domains in KDM5A have functions beyond recruitment and whether they regulate the catalytic activity of the demethylase. Here using biochemical and nuclear magnetic resonance (NMR)-based structural studies, we show that the PHD1 preferentially recognizes unmethylated H3K4 histone tail, product of KDM5A-mediated demethylation of tri-methylated H3K4 (H3K4me3). Binding of unmodified H3 peptide to the PHD1 stimulates catalytic domain-mediated removal of methyl marks from H3K4me3 peptide and nucleosome substrates. This positive-feedback mechanism—enabled by the functional coupling between a reader and a catalytic domain in KDM5A—suggests a model for the spread of demethylation on chromatin.

  5. Positive feedback, memory, and the predictability of earthquakes

    PubMed Central

    Sammis, C. G.; Sornette, D.

    2002-01-01

    We review the “critical point” concept for large earthquakes and enlarge it in the framework of so-called “finite-time singularities.” The singular behavior associated with accelerated seismic release is shown to result from a positive feedback of the seismic activity on its release rate. The most important mechanisms for such positive feedback are presented. We solve analytically a simple model of geometrical positive feedback in which the stress shadow cast by the last large earthquake is progressively fragmented by the increasing tectonic stress. PMID:11875202

  6. Regulation of alkane degradation pathway by a TetR family repressor via an autoregulation positive feedback mechanism in a Gram-positive Dietzia bacterium.

    PubMed

    Liang, Jie-Liang; Nie, Yong; Wang, Miaoxiao; Xiong, Guangming; Wang, Yi-Ping; Maser, Edmund; Wu, Xiao-Lei

    2016-01-01

    n-Alkanes are ubiquitous in nature and serve as important carbon sources for both Gram-positive and Gram-negative bacteria. Hydroxylation of n-alkanes by alkane monooxygenases is the first and most critical step in n-alkane metabolism. However, regulation of alkane degradation genes in Gram-positive bacteria remains poorly characterized. We therefore explored the transcriptional regulation of an alkB-type alkane hydroxylase-rubredoxin fusion gene, alkW1, from Dietzia sp. DQ12-45-1b. The alkW1 promoter was characterized and so was the putative TetR family regulator, AlkX, located downstream of alkW1 gene. We further identified an unusually long 48 bp inverted repeat upstream of alkW1 and demonstrated the binding of AlkX to this operator. Analytical ultracentrifugation and microcalorimetric results indicated that AlkX formed stable dimers in solution and two dimers bound to one operator in a positive cooperative fashion characterized by a Hill coefficient of 1.64 (± 0.03) [k(D)  = 1.06 (± 0.16) μM, k(D) ' = 0.05 (± 0.01) μM]. However, the DNA-binding affinity was disrupted in the presence of long-chain fatty acids (C10-C24), suggesting that AlkX can sense the concentrations of n-alkane degradation metabolites. A model was therefore proposed where AlkX controls alkW1 expression in a metabolite-dependent manner. Bioinformatic analysis revealed that the alkane hydroxylase gene regulation mechanism may be common among Actinobacteria. PMID:26418273

  7. Positive force feedback in bouncing gaits?

    PubMed Central

    Geyer, Hartmut; Seyfarth, Andre; Blickhan, Reinhard

    2003-01-01

    During bouncing gaits (running, hopping, trotting), passive compliant structures (e.g. tendons, ligaments) store and release part of the stride energy. Here, active muscles must provide the required force to withstand the developing tendon strain and to compensate for the inevitable energy losses. This requires an appropriate control of muscle activation. In this study, for hopping, the potential involvement of afferent information from muscle receptors (muscle spindles, Golgi tendon organs) is investigated using a two-segment leg model with one extensor muscle. It is found that: (i) positive feedbacks of muscle-fibre length and muscle force can result in periodic bouncing; (ii) positive force feedback (F+) stabilizes bouncing patterns within a large range of stride energies (maximum hopping height of 16.3 cm, almost twofold higher than the length feedback); and (iii) when employing this reflex scheme, for moderate hopping heights (up to 8.8 cm), an overall elastic leg behaviour is predicted (hopping frequency of 1.4-3 Hz, leg stiffness of 9-27 kN m(-1)). Furthermore, F+ could stabilize running. It is suggested that, during the stance phase of bouncing tasks, the reflex-generated motor control based on feedbacks might be an efficient and reliable alternative to central motor commands. PMID:14561282

  8. Ribosome flow model with positive feedback

    PubMed Central

    Margaliot, Michael; Tuller, Tamir

    2013-01-01

    Eukaryotic mRNAs usually form a circular structure; thus, ribosomes that terminatae translation at the 3′ end can diffuse with increased probability to the 5′ end of the transcript, initiating another cycle of translation. This phenomenon describes ribosomal flow with positive feedback—an increase in the flow of ribosomes terminating translating the open reading frame increases the ribosomal initiation rate. The aim of this paper is to model and rigorously analyse translation with feedback. We suggest a modified version of the ribosome flow model, called the ribosome flow model with input and output. In this model, the input is the initiation rate and the output is the translation rate. We analyse this model after closing the loop with a positive linear feedback. We show that the closed-loop system admits a unique globally asymptotically stable equilibrium point. From a biophysical point of view, this means that there exists a unique steady state of ribosome distributions along the mRNA, and thus a unique steady-state translation rate. The solution from any initial distribution will converge to this steady state. The steady-state distribution demonstrates a decrease in ribosome density along the coding sequence. For the case of constant elongation rates, we obtain expressions relating the model parameters to the equilibrium point. These results may perhaps be used to re-engineer the biological system in order to obtain a desired translation rate. PMID:23720534

  9. Independent modal space control with positive position feedback

    NASA Technical Reports Server (NTRS)

    Baz, A.; Poh, S.; Fedor, J.

    1989-01-01

    An independent modal space control (IMSC) algorithm is presented, whose modal control forces are generated from a positive position feedback (PPF) strategy. The proposed algorithm combines the attributes of both the IMSC and the PPF, and maintains the simplicity of the IMSC as it designs the controller of a complex structure at the uncoupled modal level. The effectiveness of the algorithm in damping out the vibration of flexible structures is validated experimentally. A simple cantilevered beam is employed as an example of a flexible structure whose multimodes of vibration are controlled by a single actuator. Performance of the active control system is determined in the frequency and the time domains. The experimental results indicate the potential of the proposed methodology as a viable method for controlling the vibration of large flexible structures.

  10. Positive Radiative-Dynamic Feedback in Martian Dust Storms

    NASA Astrophysics Data System (ADS)

    Rafkin, S. C.; Rothchild, A.; Pielke, R. A., Sr.

    2010-12-01

    This work follows from the work of Rafkin [2010] that identified a positive radiative-dynamic feedback mechanism for the growth and maintenance of Mars dust storms under idealized conditions. In this study, the feedback mechanism is explored under more realistic settings including complex background atmospheric structures, topography, thermal tidal forcing, and a variety of mesoscale circulations. As expected, the more complex situation tends to mute the evidence and the impact of the proposed feedback process. Nonetheless, telltale signatures of the feedback mechanism are present and are consistent with the findings from the idealized scenario. Mesoscale simulations at the proposed MSL landing site of Mawrth Valles serve as the foundation for feedback studies with the Mars Regional Atmospheric Modeling System. A background dust field is specified based on MGS-TES retrievals and a dynamically active perturbation dust field is superimposed. The perturbation field arises from dust lifting (both resolved and subgrid scale) and it is subject to transport, diffusion, and sedimentation; the perturbation field is allowed to evolve over time consistent with the dynamics. The dust is tracked via a bin model with 8 discrete mass bins. To test for radiative-dynamic feedback, the radiative activity of the perturbation dust can be toggled on or off. If lifted dust behaves as a passive tracer then the simulations with radiatively active perturbation dust should evolve similarly to those with radiatively inactive dust. In idealized cases, a large difference was noted between these two scenarios indicating that lifted dust was modifying the local circulation. In the realistic scenarios presented here, simulations with radiatively active dust produce a noticeable local drop in atmospheric pressure and an increase in wind speeds, particularly in dust lifting regions where atmospheric dust concentrations are maximized. Analysis of wind residuals show a tendency for rotational and

  11. The progesterone positive feedback effect in women after ovariectomy.

    PubMed

    Zavos, Apostolos; Dafopoulos, Konstantinos; Messini, Christina I; Georgoulias, Panagiotis; Verikouki, Christina; Anifandis, George; Garas, Antonios; Messinis, Ioannis E

    2013-03-01

    Various ovarian substances regulate the secretion of gonadotrophins during the menstrual cycle, but there are still several unclarified issues. The aim of this study was to investigate the positive feedback effect of progesterone during the immediate period following ovariectomy. Experiments were performed in 12 normally cycling women (aged 39-49 years). Following abdominal hysterectomy plus bilateral ovariectomy performed on cycle day 3 (day 0), the women received either estradiol via skin patches (days 0-7, n = 6, group 1) or estradiol as above plus vaginal progesterone (days 1-7, n = 6, group 2). Serum estradiol values increased similarly in the two groups. After the operation, serum progesterone levels decreased significantly in group 1, while in group 2 they remained stable becoming higher than in group 1 (p < 0.05). An LH and an FSH surge occurred in group 2 with the values after the peak returning to the pre-surge baseline. In contrast, in group 1 LH and FSH levels following an initial decrease, increased gradually until the end of the experiment. These results demonstrate that, despite a variable response to estrogens, the positive feedback effect of progesterone remained intact immediately after ovariectomy in women. It is suggested that it is the combining action of estradiol and progesterone that can ensure the expression of a positive feedback mechanism in women. PMID:23153029

  12. Distinguishing Feedback Mechanisms in Clock Models

    NASA Astrophysics Data System (ADS)

    Golden, Alexander; Lubensky, David

    Biological oscillators are very diverse but can be classified based on dynamical motifs such as type of feedback. The S. Elongatus circadian oscillator is a novel circadian oscillator that can operate at constant protein number by modifying covalent states. It can be reproduced in vitro with only 3 different purified proteins: KaiA, KaiB, and KaiC. We use computational and analytic techniques to compare models of the S. Elongatus post-translational oscillator that rely on positive feedback with models that rely on negative feedback. We show that introducing a protein that binds competitively with KaiA to the KaiB-KaiC complex can distinguish between positive and negative feedback as the primary driver of the rhythm, which has so far been difficult to address experimentally. NSF Grant DMR-1056456.

  13. Positive Feedbacks Enhance Macroalgal Resilience on Degraded Coral Reefs.

    PubMed

    Dell, Claire L A; Longo, Guilherme O; Hay, Mark E

    2016-01-01

    Many reefs have shifted from coral and fish dominated habitats to less productive macroalgal dominated habitats, and current research is investigating means of reversing this phase shift. In the tropical Pacific, overfished reefs with inadequate herbivory can become dominated by the brown alga Sargassum polycystum. This alga suppresses recruitment and survival of corals and fishes, thus limiting the potential for reef recovery. Here we investigate the mechanisms that reinforce S. polycystum dominance and show that in addition to negatively affecting other species, this species acts in a self-reinforcing manner, positively promoting survival and growth of conspecifics. We found that survival and growth of both recruit-sized and mature S. polycystum fronds were higher within Sargassum beds than outside the beds and these results were found in both protected and fished reefs. Much of this benefit resulted from reduced herbivory within the Sargassum beds, but adult fronds also grew ~50% more within the beds even when herbivory did not appear to be occurring, suggesting some physiological advantage despite the intraspecific crowding. Thus via positive feedbacks, S. polycystum enhances its own growth and resistance to herbivores, facilitating its dominance (perhaps also expansion) and thus its resilience on degraded reefs. This may be a key feedback mechanism suppressing the recovery of coral communities in reefs dominated by macroalgal beds. PMID:27186979

  14. Positive Feedbacks Enhance Macroalgal Resilience on Degraded Coral Reefs

    PubMed Central

    Dell, Claire L. A.; Longo, Guilherme O.

    2016-01-01

    Many reefs have shifted from coral and fish dominated habitats to less productive macroalgal dominated habitats, and current research is investigating means of reversing this phase shift. In the tropical Pacific, overfished reefs with inadequate herbivory can become dominated by the brown alga Sargassum polycystum. This alga suppresses recruitment and survival of corals and fishes, thus limiting the potential for reef recovery. Here we investigate the mechanisms that reinforce S. polycystum dominance and show that in addition to negatively affecting other species, this species acts in a self-reinforcing manner, positively promoting survival and growth of conspecifics. We found that survival and growth of both recruit-sized and mature S. polycystum fronds were higher within Sargassum beds than outside the beds and these results were found in both protected and fished reefs. Much of this benefit resulted from reduced herbivory within the Sargassum beds, but adult fronds also grew ~50% more within the beds even when herbivory did not appear to be occurring, suggesting some physiological advantage despite the intraspecific crowding. Thus via positive feedbacks, S. polycystum enhances its own growth and resistance to herbivores, facilitating its dominance (perhaps also expansion) and thus its resilience on degraded reefs. This may be a key feedback mechanism suppressing the recovery of coral communities in reefs dominated by macroalgal beds. PMID:27186979

  15. Alignment positioning mechanism

    NASA Technical Reports Server (NTRS)

    Fantasia, Peter M. (Inventor)

    1991-01-01

    An alignment positioning mechanism for correcting and compensating for misalignment of structures to be coupled is disclosed. The mechanism comprises a power screw with a base portion and a threaded shank portion. A mounting fixture is provided for rigidly coupling said base portion to the mounting interface of a supporting structure with the axis of the screw perpendicular thereto. A traveling ball nut threaded on the power screw is formed with an external annular arcuate surface configured in the form of a spherical segment and enclosed by a ball nut housing with a conforming arcuate surface for permitting gimballed motion thereon. The ball nut housing is provided with a mounting surface which is positionable in cooperable engagement with the mounting interface of a primary structure to be coupled to the supporting structure. Cooperative means are provided on the ball nut and ball nut housing, respectively, for positioning the ball nut and ball nut housing in relative gimballed position within a predetermined range of relative angular relationship whereby severe structural stresses due to unequal loadings and undesirable bending moments on the mechanism are avoided.

  16. Sea ice-albedo climate feedback mechanism

    SciTech Connect

    Schramm, J.L.; Curry, J.A.; Ebert, E.E.

    1995-02-01

    The sea ice-albedo feedback mechanism over the Arctic Ocean multiyear sea ice is investigated by conducting a series of experiments using several one-dimensional models of the coupled sea ice-atmosphere system. In its simplest form, ice-albedo feedback is thought to be associated with a decrease in the areal cover of snow and ice and a corresponding increase in the surface temperature, further decreasing the area cover of snow and ice. It is shown that the sea ice-albedo feedback can operate even in multiyear pack ice, without the disappearance of this ice, associated with internal processes occurring within the multiyear ice pack (e.g., duration of the snow cover, ice thickness, ice distribution, lead fraction, and melt pond characteristics). The strength of the ice-albedo feedback mechanism is compared for several different thermodynamic sea ice models: a new model that includes ice thickness distribution., the Ebert and Curry model, the Mayjut and Untersteiner model, and the Semtner level-3 and level-0 models. The climate forcing is chosen to be a perturbation of the surface heat flux, and cloud and water vapor feedbacks are inoperative so that the effects of the sea ice-albedo feedback mechanism can be isolated. The inclusion of melt ponds significantly strengthens the ice-albedo feedback, while the ice thickness distribution decreases the strength of the modeled sea ice-albedo feedback. It is emphasized that accurately modeling present-day sea ice thickness is not adequate for a sea ice parameterization; the correct physical processes must be included so that the sea ice parameterization yields correct sensitivities to external forcing. 22 refs., 6 figs., 1 tab.

  17. Mechanical feedback stabilizes budding yeast morphogenesis

    NASA Astrophysics Data System (ADS)

    Banavar, Samhita; Trogdon, Michael; Petzold, Linda; Campas, Otger

    Walled cells have the ability to remodel their shape while sustaining an internal turgor pressure that can reach values up to 10 atmospheres. This requires a tight and simultaneous regulation of cell wall assembly and mechanochemistry, but the underlying mechanisms by which this is achieved remain unclear. Using the growth of mating projections in budding yeast (S. cerevisiae) as a motivating example, we have developed a theoretical description that couples the mechanics of cell wall expansion and assembly via a mechanical feedback. In the absence of a mechanical feedback, cell morphogenesis is inherently unstable. The presence of a mechanical feedback stabilizes changes in cell shape and growth, and provides a mechanism to prevent cell lysis in a wide range of conditions. We solve for the dynamics of the system and obtain the different dynamical regimes. In particular, we show that several parameters affect the stability of growth, including the strength of mechanical feedback in the system. Finally, we compare our results to existing experimental data.

  18. A unified approach to global and local beam position feedback

    SciTech Connect

    Chung, Y.

    1994-08-01

    The Advanced Photon Source (APS) will implement both global and local beam position feedback systems to stabilize the particle and X-ray beams for the storage ring. The global feedback system uses 40 BPMs and 40 correctors per plane. Singular value decomposition (SVD) of the response matrix is used for closed orbit correction. The local feedback system uses two X-ray BPMS, two rf BPMS, and the four-magnet local bump to control the angle and displacement of the X-ray beam from a bending magnet or an insertion device. Both the global and local feedback systems are based on digital signal processing (DSP) running at 4-kHz sampling rate with a proportional, integral, and derivative (PID) control algorithm. In this paper, we will discuss resolution of the conflict among multiple local feedback systems due to local bump closure error and decoupling of the global and local feedback systems to maximize correction efficiency. In this scheme, the global feedback system absorbs the local bump closure error and the local feedback systems compensate for the effect of global feedback on the local beamlines. The required data sharing between the global and local feedback systems is done through the fiber-optically networked reflective memory.

  19. Positive feedback effect of oestradiol in superovulated women.

    PubMed

    Messinis, I E; Mademtzis, I; Zikopoulos, K; Tsahalina, E; Seferiadis, K; Tsolas, O; Templeton, A A

    1992-04-01

    To investigate the mechanism of blockage of the luteinizing hormone (LH) surge in superovulated women, six normally ovulating women were studied in three cycles: a spontaneous cycle treated with exogenous oestrogen (oestradiol benzoate cycle), a cycle treated with follicle stimulating hormone (FSH; 225 IU/day; FSH cycle) and a cycle treated with FSH plus exogenous oestrogen (FSH + oestradiol benzoate cycle). Oestradiol benzoate was injected i.m. on cycle days 4 (0800 and 2000 h), 5 (0800 h) and 6 (0800 h) at doses of 0.5, 1.0, 2.0 and 2.5 mg respectively to achieve supraphysiological levels of serum oestradiol. Exogenous oestrogen (supraphysiological oestradiol levels) induced an LH surge in all six women in the oestradiol benzoate cycles, but failed to stimulate an LH surge in three of the six patients during treatment with FSH. In three patients treated with FSH, an LH surge was stimulated both by supraphysiological (FSH + oestradiol benzoate cycles) and 'high normal' oestradiol levels (FSH cycles), while in three patients treated with FSH only, the LH surge was blocked, although the threshold level for the positive feedback effect had been exceeded by cycle day 9. We conclude that in women, supraphysiological concentrations of oestradiol exert a positive feedback effect on LH secretion. It is suggested that the occurrence of an LH surge in cycles superovulated with FSH is not dependent on serum oestradiol concentrations, but mainly on the strength of ovarian inhibitory substances. PMID:1522187

  20. Linking Nutrients to Growth through a Positive Feedback Loop.

    PubMed

    Palu, Rebecca A S; Thummel, Carl S

    2015-11-01

    In this issue of Developmental Cell, Okamoto and Nishimura (2015) identify a positive feedback loop between neuronal cells that maintains insulin signaling and growth under restricted nutritional conditions. PMID:26555046

  1. Facial Feedback Mechanisms in Autistic Spectrum Disorders

    ERIC Educational Resources Information Center

    Stel, Marielle; van den Heuvel, Claudia; Smeets, Raymond C.

    2008-01-01

    Facial feedback mechanisms of adolescents with Autistic Spectrum Disorders (ASD) were investigated utilizing three studies. Facial expressions, which became activated via automatic (Studies 1 and 2) or intentional (Study 2) mimicry, or via holding a pen between the teeth (Study 3), influenced corresponding emotions for controls, while individuals…

  2. Equilibria and stability of a class of positive feedback loops.

    PubMed

    López-Caamal, Fernando; Middleton, Richard H; Huber, Heinrich J

    2014-02-01

    Positive feedback loops are common regulatory elements in metabolic and protein signalling pathways. The length of such feedback loops determines stability and sensitivity to network perturbations. Here we provide a mathematical analysis of arbitrary length positive feedback loops with protein production and degradation. These loops serve as an abstraction of typical regulation patterns in protein signalling pathways. We first perform a steady state analysis and, independently of the chain length, identify exactly two steady states that represent either biological activity or inactivity. We thereby provide two formulas for the steady state protein concentrations as a function of feedback length, strength of feedback, as well as protein production and degradation rates. Using a control theory approach, analysing the frequency response of the linearisation of the system and exploiting the Small Gain Theorem, we provide conditions for local stability for both steady states. Our results demonstrate that, under some parameter relationships, once a biological meaningful on steady state arises, it is stable, while the off steady state, where all proteins are inactive, becomes unstable. We apply our results to a three-tier feedback of caspase activation in apoptosis and demonstrate how an intermediary protein in such a loop may be used as a signal amplifier within the cascade. Our results provide a rigorous mathematical analysis of positive feedback chains of arbitrary length, thereby relating pathway structure and stability. PMID:23358701

  3. Ultrasensitive gene regulation by positive feedback loops in nucleosome modification.

    PubMed

    Sneppen, Kim; Micheelsen, Mille A; Dodd, Ian B

    2008-01-01

    Eukaryotic transcription involves the synergistic interaction of many different proteins. However, the question remains how eukaryotic promoters achieve ultrasensitive or threshold responses to changes in the concentration or activity of a single transcription factor (TF). We show theoretically that by recruiting a histone-modifying enzyme, a TF binding non-cooperatively to a single site can change the balance between opposing positive feedback loops in histone modification to produce a large change in gene expression in response to a small change in concentration of the TF. This mechanism can also generate bistable promoter responses, allowing a gene to be on in some cells and off in others, despite the cells being in identical conditions. In addition, the system provides a simple means by which the activities of many TFs could be integrated at a promoter. PMID:18414483

  4. Position feedback system for volume holographic storage media

    DOEpatents

    Hays, Nathan J.; Henson, James A.; Carpenter, Christopher M.; Akin, Jr.. William R.; Ehrlich, Richard M.; Beazley, Lance D.

    1998-07-07

    A method of holographic recording in a photorefractive medium wherein stored holograms may be retrieved with maximum signal-to noise ratio (SNR) is disclosed. A plurality of servo blocks containing position feedback information is recorded in the crystal and made non-erasable by heating the crystal. The servo blocks are recorded at specific increments, either angular or frequency, depending whether wavelength or angular multiplexing is applied, and each servo block is defined by one of five patterns. Data pages are then recorded at positions or wavelengths enabling each data page to be subsequently reconstructed with servo patterns which provide position feedback information. The method of recording data pages and servo blocks is consistent with conventional practices. In addition, the recording system also includes components (e.g. voice coil motor) which respond to position feedback information and adjust the angular position of the reference angle of a reference beam to maximize SNR by reducing crosstalk, thereby improving storage capacity.

  5. Folding with thermal-mechanical feedback: Discussion

    NASA Astrophysics Data System (ADS)

    Treagus, Susan H.; Hudleston, Peter J.

    2009-07-01

    A recent paper in this Journal by Bruce Hobbs, Klaus Regenauer-Lieb and Alison Ord [Hobbs, B., Regenauer-Lieb, K., Ord, A., 2008. Folding with thermal-mechanical feedback. Journal of Structural Geology 30, 1572-1592] presents an alternative theory to the traditional Biot-Ramberg theory for folding of viscous rocks that involves non-equilibrium thermodynamics and thermal-mechanical feedback. The authors convey a strong message throughout their paper that the folds produced by this theoretical and numerical modelling are geologically realistic and provide a better explanation for many natural folds than the traditional theory. They promise the same approach for boudinage, and present this folding paper as part of a "unified framework for rock deformation processes". Readers of the Journal of Structural Geology might be led to conclude that this paper provides a good alternative model for folding of rocks. Our discussion will disagree, on four counts.

  6. Feedback in Action--The Mechanism of the Iris.

    ERIC Educational Resources Information Center

    Pingnet, B.; And Others

    1988-01-01

    Describes two demonstration experiments. Outlines a demonstration of the general principle of positive and negative feedback and the influence of time delays in feedback circuits. Elucidates the principle of negative feedback with a model of the iris of the eye. Emphasizes the importance of feedback in biological systems. (CW)

  7. Beam position feedback system for the Advanced Photon Source

    SciTech Connect

    Chung, Y.

    1993-12-31

    The Advanced Photon Source (APS) will implement both global and local beam position feedback systems to stabilize the particle and X-ray beams for the storage ring. The systems consist of 20 VME crates distributed around the ring, each running multiple digital signal processors (DSP) running at 4kHz sampling rate with a proportional, integral, and derivative (PID) control algorithm. The particle and X-ray beam position data is shared by the distributed processors through networked reflective memory. A theory of closed orbit correction using the technique of singular value decomposition (SVD) of the response matrix and simulation of its application to the APS storage ring will be discussed. This technique combines the global and local feedback systems and resolves the conflict among multiple local feedback systems due to local bump closure error. Maximum correction efficiency is achieved by feeding back the global orbit data to the local feedback systems. The effect of the vacuum chamber eddy current induced by the AC corrector magnet field for local feedback systems is compensated by digital filters. Results of experiments conducted on the X-ray ring of the National Synchrotron Light Source and the SPEAR at Stanford Synchrotron Radiation Laboratory will be presented.

  8. Improved Position Sensor for Feedback Control of Levitation

    NASA Technical Reports Server (NTRS)

    Hyers, Robert; Savage, Larry; Rogers, Jan

    2004-01-01

    An improved optoelectronic apparatus has been developed to provide the position feedback needed for controlling the levitation subsystem of a containerless-processing system. As explained, the advantage of this apparatus over prior optoelectronic apparatuses that have served this purpose stems from the use of an incandescent lamp, instead of a laser, to illuminate the levitated object. In containerless processing, a small object to be processed is levitated (e.g., by use of a microwave, low-frequency electromagnetic, electrostatic, or acoustic field) so that it is not in contact with the wall of the processing chamber or with any other solid object during processing. In the case of electrostatic or low-frequency electromagnetic levitation, real-time measurement of the displacement of the levitated object from its nominal levitation position along the vertical axis (and, in some cases, along one or two horizontal axes) is needed for feedback control of the levitating field.

  9. Stochastic gene expression with bursting and positive feedback

    NASA Astrophysics Data System (ADS)

    Platini, Thierry; Pendar, Hodjat; Kulkarni, Rahul

    2012-02-01

    Stochasticity (or noise) in the process of gene expression can play a critical role in cellular circuits that control switching between probabilistic cell-fate decisions in diverse organisms. Such circuits often include positive feedback loops as critical elements. In some cases (e.g. HIV-1 viral infections), switching between different cell fates occurs even in the absence of bistability in the underlying deterministic model. To characterize the role of noise in such systems, we analyze a simple gene expression circuit that includes contributions from both transcriptional and translational bursting and positive feedback effects. Using a combination of analytical approaches and stochastic simulations, we explore how the underlying parameters control the corresponding mean and variance in protein distributions.

  10. Feedback Mechanisms in a Mechanical Model of Cell Polarization

    PubMed Central

    Wang, Xinxin; Carlsson, Anders E.

    2014-01-01

    Directed cell migration requires a spatially polarized distribution of polymerized actin. We develop and treat a mechanical model of cell polarization based on polymerization and depolymerization of actin filaments at the two ends of a cell, modulated by forces at either end that are coupled by the cell membrane. We solve this model using both a simulation approach that treats filament nucleation, polymerization, and depolymerization stochastically, and a rate-equation approach based on key properties such as the number of filaments N and the number of polymerized subunits F at either end of the cell. The rate-equation approach agrees closely with the stochastic approach at steady state and, when appropriately generalized, also predicts the dynamic behavior accurately. The calculated transitions from symmetric to polarized states show that polarization is enhanced by a high free-actin concentration, a large pointed-end off-rate, a small barbed-end off-rate, and a small spontaneous nucleation rate. The rate-equation approach allows us to perform a linear-stability analysis to pin down the key interactions that drive the polarization. The polarization is driven by a positive-feedback loop having two interactions. First, an increase in F at one side of the cell lengthens the filaments and thus reduces the decay rate of N (increasing N); second, increasing N enhances F because the force per growing filament tip is reduced. We find that the transitions induced by changing system properties result from supercritical pitchfork bifurcations. The filament lifetime depends strongly on the average filament length, and this effect is crucial for obtaining polarization correctly. PMID:25313164

  11. Graded Positive Feedback in Elasmobranch Ampullae of Lorenzini

    NASA Astrophysics Data System (ADS)

    Kalmijn, Ad. J.

    2003-05-01

    The acute electrical sensitivity of marine sharks and rays is the greatest known in the Animal Kingdom. I investigate the possibility that the underlying biophysical principles are the very same as those encountered in the central nervous system of animal and man. The elasmobranch ampullae of Lorenzini detect the weak electric fields originating from the oceanic environment, whereas the nerve cells of the brain detect the electric fields arising, well, from the central nervous system. In responding to electrical signals, the cell membranes of excitable cells behave in different regions of the cell as negative or positive conductors. The negative and positive conductances in series, loaded by the cell's electrolytic environment, constitute a positive feedback circuit. The result may be of an all-or-none nature, as in peripheral nerve conduction, or of a graded nature, as in central processing. In this respect, the operation of the elasmobranch ampullae of Lorenzini is more akin to the graded, integrative processes of higher brain centers than to the conduction of nerve action potentials. Hence, the positive-feedback ampullary circuit promises to help elucidate the functioning of the central nervous system as profoundly as the squid giant axon has served to reveal the process of nervous conduction.

  12. [Feedback control mechanisms of plant cell expansion

    SciTech Connect

    Cosgrove, D.J.

    1992-01-01

    We have generated considerable evidence for the significance of wall stress relaxation in the control of plant growth and found that several agents (gibberellin, light, genetic loci for dwarf stature) influence growth rate via alteration of wall relaxation. We have refined our methods for measuring wall relaxation and, moreover, have found that wall relaxation properties bear only a distance relationship to wall mechanical properties. We have garnered novel insights into the nature of cell expansion mechanisms by analyzing spontaneous fluctuations of plant growth rate in seedlings. These experiments involved the application of mathematical techniques for analyzing growth rate fluctuations and the development of new instrumentation for measuring and forcing plant growth in a controlled fashion. These studies conclude that growth rate fluctuations generated by the plant as consequence of a feedback control system. This conclusion has important implications for the nature of wall loosening processes and demands a different framework for thinking about growth control. It also implies the existence of a growth rate sensor.

  13. Optical position feedback for electrostatically driven MOEMS scanners

    NASA Astrophysics Data System (ADS)

    Tortschanoff, A.; Baumgart, M.; Frank, A.; Wildenhain, M.; Sandner, T.; Schenk, H.; Kenda, A.

    2012-03-01

    For MOEMS devices which do not have intrinsic on-chip feedback, position information can be provided with optical methods, most simply by using a reflection from the backside of a MOEMS scanner. Measurement of timing signals using fast differential photodiodes can be used for resonant scanner mirrors performing sinusoidal motion with large amplitude. While this approach provides excellent accuracy it cannot be directly extended to arbitrary trajectories or static deflection angles. Another approach is based on the measurement of the position of the reflected laser beam with a quadrant diode. In this work, we present position sensing devices based on either principle and compare both approaches showing first experimental results from the implemented devices

  14. Local beam position feedback experiments on the ESRF storage ring

    SciTech Connect

    Chung, Y.; Kahana, E.; Kirchman, J.

    1995-06-01

    This paper describes the results of local beam position feedback experiments conducted on the ESRF storage ring using digital signal processing (DSP) under the trilateral agreement of collaboration among ESRF, APS, and SPring-8. Two rf beam position monitors (BPMS) in the, upstream and downstream of the insertion device (ID) and two x-ray BPMs in the sixth cell were used to monitor the electron beam and the x-ray beam emitted from the ID, respectively. The local bump coefficients were obtained using the technique of singular value decomposition (SVD) on the global response matrix for the bump magnets and all the available BPMs outside the local bump. The local response matrix was then obtained between the two three-magnet bumps and the position monitors. The data sampling frequency was 4 kHz and a proportional, integral, and derivative (PID) controller was used. The result indicates the closed-loop feedback bandwidth close to 100 Hz and clear attenuation ({approx} {minus}40 dB) of the 7-Hz beam motion due to girder vibration resonance. Comparison of the results using the rf BPMs and x-ray BPMs will be also discussed.

  15. The better, the bigger: The effect of graded positive performance feedback on the reward positivity.

    PubMed

    Frömer, Romy; Stürmer, Birgit; Sommer, Werner

    2016-02-01

    In this study on skill acquisition in a computerized throwing task, we examined the effect of graded correct-related performance feedback on the reward positivity of the event-related brain potential (ERP). Theories of reinforcement learning predict effects of reward magnitude and expectancy on the reward prediction error. The later is supposed to be reflected in reward positivity, a fronto-central ERP component. A sample of 68 participants learned to throw at a beamer-projected target disk while performance accuracy, displayed as the place of impact of the projectile on the target, served as graded feedback. Effects of performance accuracy in successful trials, hit frequency, and preceding trial performance on reward positivity were analyzed simultaneously on a trial-by-trial basis by means of linear mixed models. In accord with previous findings, reward positivity increased with feedback about more accurate performance. This relationship was not linear, but cubic, with larger impact of feedback towards the end of the accuracy distribution. In line with being a measure of expectancy, the reward positivity decreased with increasing hit frequency and was larger after unsuccessful trials. The effect of hit frequency was more pronounced following successful trials. These results indicate a fast trial-by-trial adaptation of expectation. The results confirm predictions of reinforcement learning theory and extend previous findings on reward magnitude to the area of complex, goal directed skill acquisition. PMID:26756995

  16. Towards positive feedbacks between vegetation and tropospheric O3

    NASA Astrophysics Data System (ADS)

    VanLoocke, A. D.; Bernacchi, C. J.; Ainsworth, E. A.; Betzelberger, A. M.

    2011-12-01

    The concentration of tropospheric ozone ([O3]) has approximately doubled since 1900 and is projected to continue increasing. The extent of this increase depends strongly on the emission of ozone precursors as well as changing temperature and humidity. The responses of vegetation to O3 may also have the potential to positively feedback on regional climate and on the cycle of O3 formation and destruction. Plant productivity is linked to feedbacks in the climate indirectly through the carbon cycle as well as directly through the partitioning of radiation into sensible and latent heat fluxes. In the troposphere, O3 reduces plant productivity, an effect that is pronounced in soybean, the 4th most important food crop in the world. The soybean-maize agro-ecosystem is the largest ecosystem in the contiguous U.S., therefore changes in productivity and water use by soybean under increasing [O3] could impact the regional climate and hydrologic cycle in Midwestern U.S. with feedback effects on tropospheric O3 production and cycling. To assess the response to increasing [O3], soybeans were grown under open-air agricultural conditions at the SoyFACE research facility. During the 2009 growing season, eight 20 m diameter plots were exposed to different [O3] ranging from 40 to 200 ppb. Measurements of leaf-level gas exchange were made on four dates throughout the growing season and non-destructive measurements of Leaf Area Index were made weekly. Canopy latent and sensible heat fluxes were measured continuously throughout the growing season (day of year 197-245) using a residual energy balance micrometeorological technique. Results show that as [O3] increased, rates of photosynthesis and stomatal conductance decreased. Productivity, (i.e. seed yield) decreased by over 60% from 40 to 200 ppb while canopy evapotranspiration decreased by 30%. Sensible heat flux increased by 30%, while the growing season average canopy temperatures increased by 1 °C and with peak increases of 2

  17. Brain activity elicited by positive and negative feedback in preschool-aged children.

    PubMed

    Mai, Xiaoqin; Tardif, Twila; Doan, Stacey N; Liu, Chao; Gehring, William J; Luo, Yue-Jia

    2011-01-01

    To investigate the processing of positive vs. negative feedback in children aged 4-5 years, we devised a prize-guessing game that is analogous to gambling tasks used to measure feedback-related brain responses in adult studies. Unlike adult studies, the feedback-related negativity (FRN) elicited by positive feedback was as large as that elicited by negative feedback, suggesting that the neural system underlying the FRN may not process feedback valence in early childhood. In addition, positive feedback, compared with negative feedback, evoked a larger P1 over the occipital scalp area and a larger positive slow wave (PSW) over the right central-parietal scalp area. We believe that the PSW is related to emotional arousal and the intensive focus on positive feedback that is present in the preschool and early school years has adaptive significance for both cognitive and emotional development during this period. PMID:21526189

  18. Brain Activity Elicited by Positive and Negative Feedback in Preschool-Aged Children

    PubMed Central

    Mai, Xiaoqin; Tardif, Twila; Doan, Stacey N.; Liu, Chao; Gehring, William J.; Luo, Yue-Jia

    2011-01-01

    To investigate the processing of positive vs. negative feedback in children aged 4–5 years, we devised a prize-guessing game that is analogous to gambling tasks used to measure feedback-related brain responses in adult studies. Unlike adult studies, the feedback-related negativity (FRN) elicited by positive feedback was as large as that elicited by negative feedback, suggesting that the neural system underlying the FRN may not process feedback valence in early childhood. In addition, positive feedback, compared with negative feedback, evoked a larger P1 over the occipital scalp area and a larger positive slow wave (PSW) over the right central-parietal scalp area. We believe that the PSW is related to emotional arousal and the intensive focus on positive feedback that is present in the preschool and early school years has adaptive significance for both cognitive and emotional development during this period. PMID:21526189

  19. Integrated packaging of 2D MOEMS mirrors with optical position feedback

    NASA Astrophysics Data System (ADS)

    Baumgart, M.; Lenzhofer, M.; Kremer, M. P.; Tortschanoff, A.

    2015-02-01

    Many applications of MOEMS microscanners rely on accurate position feedback. For MOEMS devices which do not have intrinsic on-chip feedback, position information can be provided with optical methods, most simply by using a reflection from the backside of a MOEMS scanner. By measuring the intensity distribution of the reflected beam across a quadrant diode, one can precisely detect the mirror's deflection angles. Previously, we have presented a position sensing device, applicable to arbitrary trajectories, which is based on the measurement of the position of the reflected laser beam with a quadrant diode. In this work, we present a novel setup, which comprises the optical position feedback functionality integrated into the device package itself. The new device's System-in-Package (SiP) design is based on a flip-folded 2.5D PCB layout and fully assembled as small as 9.2×7×4 mm³ in total. The device consists of four layers, which supply the MOEMS mirror, a spacer to provide the required optical path length, the quadrant photo-diode and a laser diode to serve as the light source. In addition to describing the mechanical setup of the novel device, we will present first experimental results and optical simulation studies. Accurate position feedback is the basis for closed-loop control of the MOEMS devices, which is crucial for some applications as image projection for example. Position feedback and the possibility of closed-loop control will significantly improve the performance of these devices.

  20. Understanding positive feedback between PNA and synoptic eddies by eddy structure decomposition method

    NASA Astrophysics Data System (ADS)

    Zhou, Fang; Ren, Hong-Li; Xu, Xiao-Feng; Zhou, You

    2016-08-01

    In the upper troposphere during winter, positive synoptic eddy (SE) feedback plays an indispensible role in maintaining the Pacific-North American (PNA) pattern that dominates climate variability on inter-annual timescales over the North Pacific and downstream regions. This study shows that the eddy forcing, induced by eddy-vorticity (EV) fluxes, is not only in-phase with, but also downstream to the PNA pattern in terms of its northeast Pacific lobe. We employ the eddy structure decomposition method to understand such an observed PNA-SEs feedback, and propose a kinematic mechanism that can depict dynamical processes associated with the eddy structure change and its induced positive eddy feedback relative to the PNA flow pattern. With this method, the winter-mean PNA-related SE structures are separated into climatological (basic) and anomalous SE structures, and these two parts can be used to represent the changes in SE structure in a statistical sense and then to calculate the EV fluxes in order to further elucidate the feedback mechanism. It is demonstrated that, on one hand, the winter-mean PNA flow tends to systematically deform the structures of SEs and induce anomalous EV fluxes, and these winter-mean EV fluxes primarily converge into the PNA cyclonic center, which, in return enhances the PNA flow. On the other hand, the PNA-related northeast Pacific flow is featured by a stronger zonal wind shear in the east than the west, which can induce larger zonal-slanting eddy structure change and then stronger meridional EV fluxes that converge to form downstream feedback. This kinematic mechanism may help to deeply understand the dynamical eddy feedback between the low-frequency PNA flow and high-frequency SEs.

  1. Active control of a flexible structure using a modal positive position feedback controller

    NASA Technical Reports Server (NTRS)

    Poh, S.; Baz, A.

    1990-01-01

    The feasibility of a new Modal Positive Position Feedback (MPPF) strategy in controlling the vibration of a complex flexible structure using a single piezo-electric active structural member is demonstrated. The control strategy generates its control forces by manipulating only the modal position signals of the structure to provide a damping action to undamped modes. This is in contrast to conventional modal controllers that rely in their operation on negative feedback of both the modal position and velocity. The proposed strategy is very simple to design and implement as it designs the controller at the uncoupled modal level and utilizes simple first order filters to achieve the Positive Position Feedback effect. The performance of the new strategy is enhanced by augmenting it with a time sharing strategy to share a small number of actuators between larger number of modes. The effectiveness of the new strategy is validated experimentally on a flexible box-type structure that has four bays and its first two bending modes are 2.015 and 6.535 Hz respectively. A single piezo-electric actuator is utilized as an active structural member to control several transverse bending modes of the structure. The performance of the active control system is determined in the time and the frequency domains. The results are compared with those obtained when using the Independent Modal Space Control (IMSC) of Meirovitch. The experimental results suggest the potential of the proposed strategy as a viable means for controlling the vibration of large flexible structures in real time.

  2. Active control of a flexible structure using a modal positive position feedback controller

    NASA Technical Reports Server (NTRS)

    Poh, S.; Baz, A.

    1990-01-01

    The feasibility of a new Modal Positive Position Feedback (MPPF) strategy in controlling the vibration of a complex flexible structure using a single piezo-electric active structural member is demonstrated. The control strategy generates its control forces by manipulating only the modal position signals of the structure to provide a damping action to undamped modes. This is in contrast to conventional modal controllers that rely in their operation on negative feedback of both the modal position and velocity. The proposed strategy is very simple to design and implement as it designs the controller at the uncoupled modal level and utilizes simple first order filters to achieve the Positive Position Feedback effect. The performance of the new strategy is enhanced by augmenting it with a time sharing strategy to share a small number of actuators between larger number of modes. The effectiveness of the new strategy is validated experimentally on a flexible box-type structure that has four bays and its first two bending modes are 2.015 and 6.535 Hz, respectively. A single piezo-electric actuator is utilized as an active structural member to control several transverse bending modes of the structure. The performance of the active control system is determined in the time and the frequency domains. The results are compared with those obtained when using the Independent Modal Space Control (IMSC) of Meirovitch. The experimental results suggest the potential of the proposed strategy as a viable means for controlling the vibration of large flexible structures in real time.

  3. Robust, tunable genetic memory from protein sequestration combined with positive feedback.

    PubMed

    Shopera, Tatenda; Henson, William R; Ng, Andrew; Lee, Young Je; Ng, Kenneth; Moon, Tae Seok

    2015-10-15

    Natural regulatory networks contain many interacting components that allow for fine-tuning of switching and memory properties. Building simple bistable switches, synthetic biologists have learned the design principles of complex natural regulatory networks. However, most switches constructed so far are so simple (e.g. comprising two regulators) that they are functional only within a limited parameter range. Here, we report the construction of robust, tunable bistable switches in Escherichia coli using three heterologous protein regulators (ExsADC) that are sequestered into an inactive complex through a partner swapping mechanism. On the basis of mathematical modeling, we accurately predict and experimentally verify that the hysteretic region can be fine-tuned by controlling the interactions of the ExsADC regulatory cascade using the third member ExsC as a tuning knob. Additionally, we confirm that a dual-positive feedback switch can markedly increase the hysteretic region, compared to its single-positive feedback counterpart. The dual-positive feedback switch displays bistability over a 10(6)-fold range of inducer concentrations, to our knowledge, the largest range reported so far. This work demonstrates the successful interlocking of sequestration-based ultrasensitivity and positive feedback, a design principle that can be applied to the construction of robust, tunable, and predictable genetic programs to achieve increasingly sophisticated biological behaviors. PMID:26384562

  4. Positive feedback between increasing atmospheric CO2 and ecosystem productivity

    NASA Astrophysics Data System (ADS)

    Gelfand, I.; Hamilton, S. K.; Robertson, G. P.

    2009-12-01

    Increasing atmospheric CO2 will likely affect both the hydrologic cycle and ecosystem productivity. Current assumptions that increasing CO2 will lead to increased ecosystem productivity and plant water use efficiency (WUE) are driving optimistic predictions of higher crop yields as well as greater availability of freshwater resources due to a decrease in evapotranspiration. The plant physiological response that drives these effects is believed to be an increase in carbon uptake either by (a) stronger CO2 gradient between the stomata and the atmosphere, or by (b) reduced CO2 limitation of enzymatic carboxylation within the leaf. The (a) scenario will lead to increased water use efficiency (WUE) in plants. However, evidence for increased WUE is mostly based on modeling studies, and experiments producing a short duration or step-wise increase in CO2 concentration (e.g. free-air CO2 enrichment). We hypothesize that the increase in atmospheric CO2 concentration is having a positive effect on ecosystem productivity and WUE. To investigate this hypothesis, we analyzed meteorological, ANPP, and soil CO2 flux datasets together with carbon isotopic ratio (13C/12C) of archived plant samples from the long term ecological research (LTER) program at Kellogg Biological Station. The datasets were collected between 1989 and 2007 (corresponding to an increase in atmospheric CO2 concentration of ~33 ppmv at Mauna Loa). Wheat (Triticum aestivum) samples taken from 1989 and 2007 show a significant decrease in the C isotope discrimination factor (Δ) over time. Stomatal conductance is directly related to Δ, and thus Δ is inversely related to plant intrinsic WUE (iWUE). Historical changes in the 13C/12C ratio (δ13C) in samples of a perennial forb, Canada goldenrod (Solidago canadensis), taken from adjacent successional fields, indicate changes in Δ upon uptake of CO2 as well. These temporal trends in Δ suggest a positive feedback between the increasing CO2 concentration in the

  5. Output feedback control of a mechanical system using magnetic levitation.

    PubMed

    Beltran-Carbajal, F; Valderrabano-Gonzalez, A; Rosas-Caro, J C; Favela-Contreras, A

    2015-07-01

    This paper presents an application of a nonlinear magnetic levitation system to the problem of efficient active control of mass-spring-damper mechanical systems. An output feedback control scheme is proposed for reference position trajectory tracking tasks on the flexible mechanical system. The electromagnetically actuated system is shown to be a differentially flat nonlinear system. An extended state estimation approach is also proposed to obtain estimates of velocity, acceleration and disturbance signals. The differential flatness structural property of the system is then employed for the synthesis of the controller and the signal estimation approach presented in this work. Some experimental and simulation results are included to show the efficient performance of the control approach and the effective estimation of the unknown signals. PMID:25707718

  6. Periodic explosions by positive feedback in a rising foam column

    PubMed Central

    Zener, Clarence; Noriega, Jaime

    1982-01-01

    An aqueous foam rising adiabatically in a column suffers a drop in temperature. Under appropriate conditions, such a column periodically explodes. We here trace this explosion to the tight thermal coupling between the foam and its enclosing glass column. When the surface surfactant concentration is unbuffered by micelles, a positive feedback exists between the flow of heat from the walls into the foam and the thermal conductivity of the foam itself. In our highly expanded foam, heat is conducted through the foam cells' interior primarily by the heat-pipe effect. Such an effect is retarded by a dense layer of surfactant molecules. Heat absorption causes cell expansion, which, in a foam unbuffered by micelles, causes a reduction in surface concentration of surfactant molecules and, hence, in an increase in thermal conductivity. This interpretation of our observed periodic explosions is in agreement with all of our observations. PMID:16593192

  7. BLOWIN' IN THE WIND: BOTH ''NEGATIVE'' AND ''POSITIVE'' FEEDBACK IN AN OBSCURED HIGH-z QUASAR

    SciTech Connect

    Cresci, G.; Mannucci, F.; Mainieri, V.; Brusa, M.; Perna, M.; Lanzuisi, G.; Piconcelli, E.; Feruglio, C.; Fiore, F.; Bongiorno, A.; Maiolino, R.; Merloni, A; Schramm, M.; Silverman, J. D.; Civano, F.

    2015-01-20

    Quasar feedback in the form of powerful outflows is invoked as a key mechanism to quench star formation in galaxies, preventing massive galaxies to overgrow and producing the red colors of ellipticals. On the other hand, some models are also requiring ''positive'' active galactic nucleus feedback, inducing star formation in the host galaxy through enhanced gas pressure in the interstellar medium. However, finding observational evidence of the effects of both types of feedback is still one of the main challenges of extragalactic astronomy, as few observations of energetic and extended radiatively driven winds are available. Here we present SINFONI near infrared integral field spectroscopy of XID2028, an obscured, radio-quiet z = 1.59 QSO detected in the XMM-COSMOS survey, in which we clearly resolve a fast (1500 km s{sup –1}) and extended (up to 13 kpc from the black hole) outflow in the [O III] lines emitting gas, whose large velocity and outflow rate are not sustainable by star formation only. The narrow component of Hα emission and the rest frame U-band flux from Hubble Space Telescope/Advanced Camera for Surveys imaging enable to map the current star formation in the host galaxy: both tracers independently show that the outflow position lies in the center of an empty cavity surrounded by star forming regions on its edge. The outflow is therefore removing the gas from the host galaxy (''negative feedback''), but also triggering star formation by outflow induced pressure at the edges (''positive feedback''). XID2028 represents the first example of a host galaxy showing both types of feedback simultaneously at work.

  8. Blowin' in the Wind: Both "Negative" and "Positive" Feedback in an Obscured High-z Quasar

    NASA Astrophysics Data System (ADS)

    Cresci, G.; Mainieri, V.; Brusa, M.; Marconi, A.; Perna, M.; Mannucci, F.; Piconcelli, E.; Maiolino, R.; Feruglio, C.; Fiore, F.; Bongiorno, A.; Lanzuisi, G.; Merloni, A.; Schramm, M.; Silverman, J. D.; Civano, F.

    2015-01-01

    Quasar feedback in the form of powerful outflows is invoked as a key mechanism to quench star formation in galaxies, preventing massive galaxies to overgrow and producing the red colors of ellipticals. On the other hand, some models are also requiring "positive" active galactic nucleus feedback, inducing star formation in the host galaxy through enhanced gas pressure in the interstellar medium. However, finding observational evidence of the effects of both types of feedback is still one of the main challenges of extragalactic astronomy, as few observations of energetic and extended radiatively driven winds are available. Here we present SINFONI near infrared integral field spectroscopy of XID2028, an obscured, radio-quiet z = 1.59 QSO detected in the XMM-COSMOS survey, in which we clearly resolve a fast (1500 km s-1) and extended (up to 13 kpc from the black hole) outflow in the [O III] lines emitting gas, whose large velocity and outflow rate are not sustainable by star formation only. The narrow component of Hα emission and the rest frame U-band flux from Hubble Space Telescope/Advanced Camera for Surveys imaging enable to map the current star formation in the host galaxy: both tracers independently show that the outflow position lies in the center of an empty cavity surrounded by star forming regions on its edge. The outflow is therefore removing the gas from the host galaxy ("negative feedback"), but also triggering star formation by outflow induced pressure at the edges ("positive feedback"). XID2028 represents the first example of a host galaxy showing both types of feedback simultaneously at work.

  9. The Effect of Positive Feedback in a Constraint-Based Intelligent Tutoring System

    ERIC Educational Resources Information Center

    Mitrovic, Antonija; Ohlsson, Stellan; Barrow, Devon K.

    2013-01-01

    Tutoring technologies for supporting learning from errors via negative feedback are highly developed and have proven their worth in empirical evaluations. However, observations of empirical tutoring dialogs highlight the importance of positive feedback in the practice of expert tutoring. We hypothesize that positive feedback works by reducing…

  10. From Positivity to Negativity Bias: Ambiguity Affects the Neurophysiological Signatures of Feedback Processing.

    PubMed

    Gibbons, Henning; Schnuerch, Robert; Stahl, Jutta

    2016-04-01

    Previous studies on the neurophysiological underpinnings of feedback processing almost exclusively used low-ambiguity feedback, which does not fully address the diversity of situations in everyday life. We therefore used a pseudo trial-and-error learning task to investigate ERPs of low- versus high-ambiguity feedback. Twenty-eight participants tried to deduce the rule governing visual feedback to their button presses in response to visual stimuli. In the blocked condition, the same two feedback words were presented across several consecutive trials, whereas in the random condition feedback was randomly drawn on each trial from sets of five positive and five negative words. The feedback-related negativity (FRN-D), a frontocentral ERP difference between negative and positive feedback, was significantly larger in the blocked condition, whereas the centroparietal late positive complex indicating controlled attention was enhanced for negative feedback irrespective of condition. Moreover, FRN-D in the blocked condition was due to increased reward positivity (Rew-P) for positive feedback, rather than increased (raw) FRN for negative feedback. Our findings strongly support recent lines of evidence that the FRN-D, one of the most widely studied signatures of reinforcement learning in the human brain, critically depends on feedback discriminability and is primarily driven by the Rew-P. A novel finding concerned larger frontocentral P2 for negative feedback in the random but not the blocked condition. Although Rew-P points to a positivity bias in feedback processing under conditions of low feedback ambiguity, P2 suggests a specific adaptation of information processing in case of highly ambiguous feedback, involving an early negativity bias. Generalizability of the P2 findings was demonstrated in a second experiment using explicit valence categorization of highly emotional positive and negative adjectives. PMID:26765948

  11. Active vibration suppression through positive acceleration feedback on a building-like structure: An experimental study

    NASA Astrophysics Data System (ADS)

    Enríquez-Zárate, J.; Silva-Navarro, G.; Abundis-Fong, H. F.

    2016-05-01

    This work deals with the structural and dynamic analysis of a building-like structure consisting of a three-story building with one active vibration absorber. The base of the structure is perturbed using an electromagnetic shaker, which provides forces with a wide range of excitation frequencies, including some resonance frequencies of the structure. One beam-column of the structure is coupled with a PZT stack actuator to reduce the vibrations. The overall mechanical structure is modeled using Euler-Lagrange methodology and validated using experimental modal analysis and Fine Element Method (FEM) techniques. The active control laws are synthesized to actively attenuate the vibration system response via the PZT stack actuator, caused by excitation forces acting on the base of the structure. The control scheme is obtained using Positive Acceleration Feedback (PAF) and Multiple Positive Acceleration Feedback (MPAF) to improve the closed-loop system response. Some experimental results are included to illustrate the overall system performance.

  12. Treatment with a position feedback-controlled head stabilizer.

    PubMed

    Harris, F A

    1979-08-01

    A position feedback-controlled head stabilizer has been developed to provide cerebral palsied individuals with resistive exercise to strengthen the neck musculature. This apparatus detects "involuntary" head motion and stabilizes the head by applying opposing forces; it also can be used to facilitate muscular contraction by resisting the subject's voluntary movements. The purpose of the present study was to determine whether voluntary head control in cerebral palsied individuals can be improved through systematic exercise using the stabilizer to strengthen the muscles of the neck and improve their balance of action. The findings support the author's contention that this is possible. The apparatus consists of a helmet and shoulder pads, interconnected so that the head is supported in the helmet by a manipulator arm. At its lower end, the manipulator arm is attached to the shoulder pad mounting frame via a gimbal assembly which allows head movement in two planes of tilt (pitch, or forward-and back, and roll, or side-to-side). Feedback control circuitry is so arranged that any deviation of the head from the desired position leads to actuation of pneumatic cylinders, which apply torques to the manipulator gimbal axes so as to oppose or conteract the incipient head movement. It is particularly significant that none of these patients participating in these experiments were at all apprehensive about or resisted being placed in the apparatus. (Even the youngest subject to use the apparatus--five year old-- did not mind being restrained by the shoulder pads or having his head gripped by helment.) While JG utilized the safety release valve quite often during the first few head control training sessions, he soon became confident enough in the action of the stabilizer that he did not even bother to grip the handle of the release valve. While DA had the action of safety valve explained and demonstrated for her, she never bothered to use it even from the outset of her experience

  13. FEEDBACK FROM CENTRAL BLACK HOLES IN ELLIPTICAL GALAXIES. II. CAN PURELY MECHANICAL ENERGY FEEDBACK MODELS WORK?

    SciTech Connect

    Shin Minsu; Ostriker, Jeremiah P.; Ciotti, Luca

    2010-03-01

    By using high-resolution one-dimensional hydrodynamical simulations, we investigate the effects of purely mechanical feedback from super massive black holes (SMBHs) in the evolution of elliptical galaxies for a broad range of feedback efficiencies and compare the results to four major observational constraints. In particular, we focus on (1) the central black hole to stellar mass ratio of the host galaxy, (2) the lifetime of the luminous quasar phase, (3) the mass of stars formed in the host galaxy within the last Gyr, and (4) the X-ray luminosity of the hot diffuse gas. As a result, we try to pin down the most successful range of mechanical feedback efficiencies. We find that while low feedback efficiencies result in too much growth of the SMBH, high efficiencies totally blow out the hot interstellar gas, and the models are characterized by very low thermal X-ray luminosity well below the observed range. The net lifetime of the quasar phase is strongly coupled to the mass ratio between SMBH and its host galaxy, while the X-ray luminosity is generally correlated to the recent star formation within the last Gyr. When considering the popularly adopted model of the constant feedback efficiency, the feedback energy deposited into the ambient medium should be more than 0.01% of the SMBH accretion energy to be consistent with the SMBH mass to stellar mass ratio in the local universe. Yet, the X-ray luminosity of the hot gas favors about 0.005% of the accretion energy as the mechanical active galactic nucleus (AGN) feedback energy. We conclude that the purely mechanical feedback mode is unlikely to be simultaneously compatible with all four observable tests, even allowing a broad range of feedback efficiencies, and that including both radiative and mechanical feedback together may be a solution to comply with the observational constraints. In addition to the adopted observational constraints, our simulations also show that the ratio of SMBH growth rate over its current

  14. Feedback mechanism for smart nozzles and nebulizers

    DOEpatents

    Montaser, Akbar [Potomac, MD; Jorabchi, Kaveh [Arlington, VA; Kahen, Kaveh [Kleinburg, CA

    2009-01-27

    Nozzles and nebulizers able to produce aerosol with optimum and reproducible quality based on feedback information obtained using laser imaging techniques. Two laser-based imaging techniques based on particle image velocimetry (PTV) and optical patternation map and contrast size and velocity distributions for indirect and direct pneumatic nebulizations in plasma spectrometry. Two pulses from thin laser sheet with known time difference illuminate droplets flow field. Charge coupled device (CCL)) captures scattering of laser light from droplets, providing two instantaneous particle images. Pointwise cross-correlation of corresponding images yields two-dimensional velocity map of aerosol velocity field. For droplet size distribution studies, solution is doped with fluorescent dye and both laser induced florescence (LIF) and Mie scattering images are captured simultaneously by two CCDs with the same field of view. Ratio of LIF/Mie images provides relative droplet size information, then scaled by point calibration method via phase Doppler particle analyzer.

  15. A positive feedback at the cellular level promotes robustness and modulation at the circuit level.

    PubMed

    Dethier, Julie; Drion, Guillaume; Franci, Alessio; Sepulchre, Rodolphe

    2015-10-01

    This article highlights the role of a positive feedback gating mechanism at the cellular level in the robustness and modulation properties of rhythmic activities at the circuit level. The results are presented in the context of half-center oscillators, which are simple rhythmic circuits composed of two reciprocally connected inhibitory neuronal populations. Specifically, we focus on rhythms that rely on a particular excitability property, the postinhibitory rebound, an intrinsic cellular property that elicits transient membrane depolarization when released from hyperpolarization. Two distinct ionic currents can evoke this transient depolarization: a hyperpolarization-activated cation current and a low-threshold T-type calcium current. The presence of a slow activation is specific to the T-type calcium current and provides a slow positive feedback at the cellular level that is absent in the cation current. We show that this slow positive feedback is required to endow the network rhythm with physiological modulation and robustness properties. This study thereby identifies an essential cellular property to be retained at the network level in modeling network robustness and modulation. PMID:26311181

  16. Input overload: Contributions of retinoic acid signaling feedback mechanisms to heart development and teratogenesis.

    PubMed

    D'Aniello, Enrico; Waxman, Joshua S

    2015-03-01

    Appropriate levels of retinoic acid (RA) signaling are critical for normal heart development in vertebrates. A fascinating property of RA signaling is the thoroughness by which positive and negative feedback are employed to promote proper embryonic RA levels. In the present short review, we first cover the advancement of hypotheses regarding the impact of RA signaling on cardiac specification. We then discuss our current understanding of RA signaling feedback mechanisms and the implications of recent studies, which have indicated improperly maintained RA signaling feedback can be a contributing factor to developmental malformations. PMID:25418431

  17. Estrogen positive feedback on LH secretion in transsexuality.

    PubMed

    Gooren, L J; Rao, B R; van Kessel, H; Harmsen-Louman, W

    1984-01-01

    In order to test the hypothesis whether there is variation in hormonal levels or response to hormonal manipulation that could permit a distinction between heterosexuals and transsexuals, we designed the following protocol: Six male-to-female (m-to-f) transsexuals, six heterosexual control females and six female-to-male (f-to-m) transsexuals were given estradiol benzoate (E2B) (4.5 micrograms/kg/12 hr) for five days. In the female population, E2B treatment was initiated on day 5 of the menstrual cycle. In all the subjects blood luteinizing hormone (LH) and follicle stimulating hormone (FSH), estradiol-17 beta (E2) and testosterone (T) levels were measured twice daily. Additionally, LH and FSH responses to LHRH (100 micrograms iv) stimulation prior to and on day 5 of the E2B treatment were evaluated. In the m-to-f transsexuals, T levels decreased sharply and progressively during estrogen treatment, along with a fall in LH and FSH levels. The magnitude of the LH and FSH responses to LHRH stimulation also decreased following estrogen administration. In the heterosexual female controls and in the f-to-m transsexuals, estrogen administration increased LH levels to a minimum of 100% above initial values from day 3 onwards. Interestingly, the magnitude of the LH increase in the f-to-m transsexuals was greater than that of the heterosexual female controls. In both groups, LHRH stimulation resulted in a greater LH response compared to that prior to estrogen treatment. Our present observations, based on blood hormonal levels and responses to hormonal manipulations do not permit a distinction between heterosexual females and f-to-m transsexuals. There was no convincing evidence for the existence of a positive estrogen feedback on LH secretion in m-to-f transsexuals. These results contradict some of the reported hypotheses concerning hormonal alterations in these individuals. PMID:6436856

  18. Positive feedbacks to growth of an invasive grass through alteration of nitrogen cycling.

    PubMed

    Lee, Marissa R; Flory, S Luke; Phillips, Richard P

    2012-10-01

    Understanding the mechanisms by which invasive plants maintain dominance is essential to achieving long-term restoration goals. While many reports have suggested invasive plants alter resource availability, experimental tests of feedbacks between invasive plants and soil resources are lacking. We used field observations and experimental manipulations to test if the invasive grass Microstegium vimineum both causes and benefits from altered soil nitrogen (N) cycling. To quantify M. vimineum effects on N dynamics, we compared inorganic N pools and nitrification rates in 20 naturally invaded and uninvaded plots across a range of mixed hardwood forests, and in experimentally invaded and uninvaded common garden plots. Potential nitrification rates were 142 and 63 % greater in invaded than uninvaded plots in forest and common garden soils, respectively. As a result, soil nitrate was the dominant form of inorganic N during peak M. vimineum productivity in both studies. To determine the response of M. vimineum to altered nitrogen availability, we manipulated the dominant N form (nitrate or ammonium) in greenhouse pots containing M. vimineum alone, M. vimineum with native species, and native species alone. M. vimineum productivity was highest in monocultures receiving nitrate; in contrast, uninvaded native communities showed no response to N form. Notably, the positive response of M. vimineum to nitrate was not apparent when grown in competition with natives, suggesting an invader density threshold is required before positive feedbacks occur. Collectively, our results demonstrate that persistence of invasive plants can be promoted by positive feedbacks with soil resources but that the magnitude of feedbacks may depend on interspecific interactions. PMID:22526935

  19. Competing Positive and Negative Feedbacks on Glacier Response to Climatic Changes

    NASA Astrophysics Data System (ADS)

    Rupper, S.; Todd, C. E.

    2009-12-01

    The adiabatic temperature lapse rate imparts a well-studied positive feedback on glacier changes in response to a given change in climate. For example, if temperature increases, the surface of the glacier thins into the warmer temperatures of the lower surface elevation, dependent upon the local lapse rate, which amplifies the glacier response to the original temperature. However, a less well-quantified negative feedback can also be at play. As the length and thickness of a valley glacier changes, the percentage of the glacier surface that is shaded changes as well, decreasing the incident shortwave radiation at the surface. Assuming turbulent heat fluxes are small, the balance between changing downward longwave radiation (adiabatic lapse rate effect) and shortwave radiation (shading effect) in response to a climatic change will determine the equilibrium glacier profile for the new climate state. Here we use an energy balance model to determine the sensitivity of glacial retreat reconstructions to both the temperature lapse rate and the shading by valley topography. We quantify the effect of shading and lapse rates on idealized glaciers and topography, and assess under what conditions one or the other feedback mechanism is expected to dominate the change in energy balance. We then examine the effect of temperature lapse rates and increased shading on a paleoglacier at Monroe Peak, in the Sevier Plateau, Utah. Although the peak is currently ice-free, lateral moraines on Monroe Peak show that a glacier once extended approximately 4000 m from a 4700 m high headwall on the western side of the peak. Preliminary results suggest that as the glacier retreated from its maximum position, increased shading had a significant positive effect on glacial mass balance which partially compensated for the lapse rate feedback. These preliminary results suggest that reconstructions of smaller glaciers surrounded by steep topography must account for changes in shading of the glacier

  20. Positive feedback and momentum growth during debris-flow entrainment of wet bed sediment

    USGS Publications Warehouse

    Iverson, R.M.; Reid, M.E.; Logan, M.; LaHusen, R.G.; Godt, J.W.; Griswold, J.P.

    2011-01-01

    Debris flows typically occur when intense rainfall or snowmelt triggers landslides or extensive erosion on steep, debris-mantled slopes. The flows can then grow dramatically in size and speed as they entrain material from their beds and banks, but the mechanism of this growth is unclear. Indeed, momentum conservation implies that entrainment of static material should retard the motion of the flows if friction remains unchanged. Here we use data from large-scale experiments to assess the entrainment of bed material by debris flows. We find that entrainment is accompanied by increased flow momentum and speed only if large positive pore pressures develop in wet bed sediments as the sediments are overridden by debris flows. The increased pore pressure facilitates progressive scour of the bed, reduces basal friction and instigates positive feedback that causes flow speed, mass and momentum to increase. If dryer bed sediment is entrained, however, the feedback becomes negative and flow momentum declines. We infer that analogous feedbacks could operate in other types of gravity-driven mass flow that interact with erodible beds. ?? 2011 Macmillan Publishers Limited. All rights reserved.

  1. Is Positive Feedback a Forgotten Classroom Practice? Findings and Implications for At-Risk Students

    ERIC Educational Resources Information Center

    Sprouls, Katie; Mathur, Sarup R.; Upreti, Gita

    2015-01-01

    Although using higher rates of positive to negative feedback is one best practice often recommended to teachers, particularly when it comes to students experiencing behavioral problems in classroom settings, research on the use of positive feedback in classroom teaching practice has revealed inconsistent results. Research has documented…

  2. System justification and electrophysiological responses to feedback: support for a positivity bias.

    PubMed

    Tritt, Shona M; Page-Gould, Elizabeth; Peterson, Jordan B; Inzlicht, Michael

    2014-06-01

    Conservatives, compared to liberals, are consistently found to exhibit physiological sensitivity to aversive stimuli. However, it remains unknown whether conservatives are also sensitive to salient positively valenced stimuli. We therefore used event-related potentials to determine the relationship between system justification (SJ), a fundamental component of conservative political ideology, and neural processing of negative and positive feedback. Participants (N = 29) filled out questionnaire assessments of SJ. Feedback-related negativity (FRN), an event-related potential component thought to index activity in neural regions associated with reward processing, was assessed in response to positive and negative feedback on a time estimation task. A significant interaction was noted between SJ and feedback type in predicting FRN. Simple effects tests suggested that SJ predicted greater FRN in response to positive but not to negative feedback. Conservatives may experience salient positive information with a heightened intensity. PMID:24274321

  3. Oscillatory profiles of positive, negative and neutral feedback stimuli during adaptive decision making.

    PubMed

    Li, Peng; Baker, Travis E; Warren, Chris; Li, Hong

    2016-09-01

    The electrophysiological response to positive and negative feedback during reinforcement learning has been well documented over the past two decades, yet, little is known about the neural response to uninformative events that often follow our actions. To address this issue, we recorded the electroencephalograph (EEG) during a time-estimation task using both informative (positive and negative) and uninformative (neutral) feedback. In the time-frequency domain, uninformative feedback elicited significantly less induced beta-gamma activity than informative feedback. This result suggests that beta-gamma activity is particularly sensitive to feedback that can guide behavioral adjustments, consistent with other work. In contrast, neither theta nor delta activity were sensitive to the difference between negative and neutral feedback, though both frequencies discriminated between positive, and non-positive (neutral or negative) feedback. Interestingly, in the time domain, we observed a linear relationship in the amplitude of the feedback-related negativity (neutral>negative>positive), a component of the event-related brain potential thought to index a specific kind of reinforcement learning signal called a reward prediction error. Taken together, these results suggest that the reinforcement learning system treats neutral feedback as a special case, providing valuable information about the electrophysiological measures used to index the cognitive function of frontal midline cortex. PMID:27378537

  4. Through-wafer optical probe characterization for microelectromechanical systems positional state monitoring and feedback control

    NASA Astrophysics Data System (ADS)

    Dawson, Jeremy M.; Chen, Jingdong; Brown, Kolin S.; Famouri, Parviz F.; Hornak, Lawrence A.

    2000-12-01

    Implementation of closed-loop microelectromechanical system (MEMS) control enables mechanical microsystems to adapt to the demands of the environment that they are actuating, opening a broad range of new opportunities for future MEMS applications. Integrated optical microsystems have the potential to enable continuous in situ optical interrogation of MEMS microstructure position fully decoupled from the means of mechanical actuation that is necessary for realization of feedback control. We present the results of initial research evaluating through-wafer optical microprobes for surface micromachined MEMS integrated optical position monitoring. Results from the through-wafer free-space optical probe of a lateral comb resonator fabricated using the multiuser MEMS process service (MUMPS) indicate significant positional information content with an achievable return probe signal dynamic range of up to 80% arising from film transmission contrast. Static and dynamic deflection analysis and experimental results indicate a through-wafer probe positional signal sensitivity of 40 mV/micrometers for the present setup or 10% signal change per micrometer. A simulation of the application of nonlinear sliding control is presented illustrating position control of the lateral comb resonator structure given the availability of positional state information.

  5. A Relevance Feedback Mechanism for Content-Based Image Retrieval.

    ERIC Educational Resources Information Center

    Ciocca, G.; Schettini, R.

    1999-01-01

    Describes a relevance-feedback mechanism for content-based image retrieval that evaluates the feature distributions of the images judged relevant by the user and updates both the similarity measure and the query to accurately represent the user's information needs. (Author/LRW)

  6. Positive feedback can lead to dynamic nanometer-scale clustering on cell membranes

    NASA Astrophysics Data System (ADS)

    Wehrens, Martijn; ten Wolde, Pieter Rein; Mugler, Andrew

    2014-11-01

    Clustering of molecules on biological membranes is a widely observed phenomenon. A key example is the clustering of the oncoprotein Ras, which is known to be important for signal transduction in mammalian cells. Yet, the mechanism by which Ras clusters form and are maintained remains unclear. Recently, it has been discovered that activated Ras promotes further Ras activation. Here we show using particle-based simulation that this positive feedback is sufficient to produce persistent clusters of active Ras molecules at the nanometer scale via a dynamic nucleation mechanism. Furthermore, we find that our cluster statistics are consistent with experimental observations of the Ras system. Interestingly, we show that our model does not support a Turing regime of macroscopic reaction-diffusion patterning, and therefore that the clustering we observe is a purely stochastic effect, arising from the coupling of positive feedback with the discrete nature of individual molecules. These results underscore the importance of stochastic and dynamic properties of reaction diffusion systems for biological behavior.

  7. Positive feedback can lead to dynamic nanometer-scale clustering on cell membranes

    SciTech Connect

    Wehrens, Martijn; Rein ten Wolde, Pieter; Mugler, Andrew

    2014-11-28

    Clustering of molecules on biological membranes is a widely observed phenomenon. A key example is the clustering of the oncoprotein Ras, which is known to be important for signal transduction in mammalian cells. Yet, the mechanism by which Ras clusters form and are maintained remains unclear. Recently, it has been discovered that activated Ras promotes further Ras activation. Here we show using particle-based simulation that this positive feedback is sufficient to produce persistent clusters of active Ras molecules at the nanometer scale via a dynamic nucleation mechanism. Furthermore, we find that our cluster statistics are consistent with experimental observations of the Ras system. Interestingly, we show that our model does not support a Turing regime of macroscopic reaction-diffusion patterning, and therefore that the clustering we observe is a purely stochastic effect, arising from the coupling of positive feedback with the discrete nature of individual molecules. These results underscore the importance of stochastic and dynamic properties of reaction diffusion systems for biological behavior.

  8. Coordination between digit forces and positions: interactions between anticipatory and feedback control.

    PubMed

    Fu, Qiushi; Santello, Marco

    2014-04-01

    Humans adjust digit forces to compensate for trial-to-trial variability in digit placement during object manipulation, but the underlying control mechanisms remain to be determined. We hypothesized that such digit position/force coordination was achieved by both visually guided feed-forward planning and haptic-based feedback control. The question arises about the time course of the interaction between these two mechanisms. This was tested with a task in which subjects generated torque (± 70 N·mm) on a virtual object to control a cursor moving to target positions to catch a falling ball, using a virtual reality environment and haptic devices. The width of the virtual object was varied between large (L) and small (S). These object widths result in significantly different horizontal digit relative positions and require different digit forces to exert the same task torque. After training, subjects were tested with random sequences of L and S widths with or without visual information about object width. We found that visual cues allowed subjects to plan manipulation forces before contact. In contrast, when visual cues were not available to predict digit positions, subjects implemented a "default" digit force plan that was corrected after digit contact to eventually accomplish the task. The time course of digit forces revealed that force development was delayed in the absence of visual cues. Specifically, the appropriate digit force adjustments were made 250-300 ms after initial object contact. This result supports our hypothesis and further reveals that haptic feedback alone is sufficient to implement digit force-position coordination. PMID:24401711

  9. Linkages of plant-soil feedbacks and underlying invasion mechanisms.

    PubMed

    Inderjit; Cahill, James F

    2015-01-01

    Soil microbial communities and processes have repeatedly been shown to impact plant community assembly and population growth. Soil-driven effects may be particularly pronounced with the introduction of plants to non-native ranges, as introduced plants are not typically accompanied by transference of local soil communities. Here we describe how the mechanisms by which soil community processes influence plant growth overlap with several known and well-described mechanisms of plant invasion. Critically, a given soil community process may either facilitate or limit invasion, depending upon local conditions and the specific mechanisms of soil processes involved. Additionally, as soil communities typically consist of species with short generation times, the net consequences of plant-soil feedbacks for invasion trajectories are likely to change over time, as ecological and evolutionary adjustments occur. Here we provide an overview of the ecological linkages of plant-soil feedbacks and underlying mechanisms of invasion. PMID:25784668

  10. Eco-hydrological feedback mechanisms control ecological services in wetlands

    NASA Astrophysics Data System (ADS)

    Coletti, J.; Hinz, C.; Vogwill, R.; Tareque, H.; Hipsey, M. R.

    2011-12-01

    Wetland ecosystems contain various feedback mechanisms between their abiotc and biotic components. The feedbacks are triggered by climate and propagate into patterns of environment partitioning based on distinct zones of hydrological function that vary in time and space. This partitioning co-evolves with vegetation, defines carbon metabolism and creates niches that govern patterns of flora and fauna abundance and distribution. Using a minimalistic model for wetland eco-hydrology, we explore vegetation adaptation to climate variability and the net metabolism of a wetland ecosystem given a range of climate conditions. We then apply the model to characterize the changes in niche habitat availability for a tortoise population endangered by a drying climate.

  11. Processing of Positive and Negative Feedback in Patients with Cerebellar Lesions.

    PubMed

    Rustemeier, Martina; Koch, Benno; Schwarz, Michael; Bellebaum, Christian

    2016-08-01

    It is well accepted that the cerebellum plays a crucial role in the prediction of the sensory consequences of movements. Recent findings of altered error processing in patients with selective cerebellar lesions led to the hypothesis that feedback processing and feedback-based learning might be affected by cerebellar damage as well. Thus, the present study investigated learning from and processing of positive and negative feedback in 12 patients with selective cerebellar lesions and healthy control subjects. Participants performed a monetary feedback learning task. The processing of positive and negative feedback was assessed by means of event-related potentials (ERPs) during the learning task and during a separate task in which the frequencies of positive and negative feedback were balanced. Patients did not show a general learning deficit compared to controls. Relative to the control group, however, patients with cerebellar lesions showed significantly higher ERP difference wave amplitudes (rewards-losses) in a time window between 250 and 450 ms after feedback presentation, possibly indicating impaired outcome prediction. The analysis of the original waveforms suggested that patients and controls primarily differed in their pattern of feedback-related negativity and P300 amplitudes. Our results add to recent findings on altered performance monitoring associated with cerebellar damage and demonstrate, for the first time, alterations of feedback processing in patients with cerebellar damage. Unaffected learning performance appears to suggest that chronic cerebellar lesions can be compensated in behaviour. PMID:26208703

  12. Active vibration control of a sandwich plate by non-collocated positive position feedback

    NASA Astrophysics Data System (ADS)

    Ferrari, Giovanni; Amabili, Marco

    2015-04-01

    The active vibration control of a free rectangular sandwich plate by using the Positive Position Feedback (PPF) algorithm was experimentally investigated in a previous study. Four normal modes were controlled by four nearly collocated couples of piezoelectric sensors and actuators. The experimental results of the control showed some limitation, especially in the Multi-Input Multi-Output (MIMO) configuration. This was attributed to the specific type of sensors and their conditioning, as well as to the phase shifts present in the vibration at different points of the structure. An alternative approach is here undertaken by abandoning the configuration of quasi-perfect collocation between sensor and actuator. The positioning of the piezoelectric patches is still led by the strain energy value distribution on the plate; each couple of sensor and actuator is now placed on the same face of the plate but in two distinct positions, opposed and symmetrical with respect to the geometric center of the plate. Single-Input Single-Output (SISO) PPF is tested and the transfer function parameters of the controller are tuned according to the measured values of modal damping. Then the participation matrices necessary for the MIMO control algorithm are determined by means of a completely experimental procedure. PPF is able to mitigate the vibration of the first four natural modes, in spite of the rigid body motions due to the free boundary conditions. The amplitude reduction achieved with the non-collocated configuration is much larger than the one obtained with the nearby collocated one. The phase lags were addressed in the MIMO algorithm by correction phase delays, further increasing the performance of the controller.

  13. Noise-controlled bistability in an excitable system with positive feedback

    NASA Astrophysics Data System (ADS)

    Kromer, Justus A.; Pinto, Reynaldo D.; Lindner, Benjamin; Schimansky-Geier, Lutz

    2014-10-01

    We study the interplay between noise and a positive feedback mechanism in an excitable system that generates events. We show that such a system can exhibit a bistability in the dynamics of the event generation (states of low and high activity). The stability of the two states is determined by the strength of the noise such that a change of noise intensity permits complete control over the probabilities with which the two states are occupied. The bistability also has strong implications for the regularity of the event generation. While the irregularity of the interevent interval (short-time variability) and the asymptotic Fano factor of the event count (long-time variability) are limited if the system is only in one of the two states, we show that both measures of variability display giant values if both states are equally likely. The long-time variability is additionally amplified by long-range positive correlations of the interevent intervals.

  14. Understanding Informal Feedback Seeking in the Workplace: The Impact of the Position in the Organizational Hierarchy

    ERIC Educational Resources Information Center

    van der Rijt, Janine; Van den Bossche, Piet; Segers, Mien S. R.

    2013-01-01

    Purpose: The purpose of this study is to investigate whether the position of employees in the organizational hierarchy is important in explaining their feedback seeking behaviour. Design/methodology/approach: This study takes a social network perspective by using an ego-centric network survey to investigate employees' feedback seeking behaviour…

  15. Consensus positive position feedback control for vibration attenuation of smart structures

    NASA Astrophysics Data System (ADS)

    Omidi, Ehsan; Nima Mahmoodi, S.

    2015-04-01

    This paper presents a new network-based approach for active vibration control in smart structures. In this approach, a network with known topology connects collocated actuator/sensor elements of the smart structure to one another. Each of these actuators/sensors, i.e., agent or node, is enhanced by a separate multi-mode positive position feedback (PPF) controller. The decentralized PPF controlled agents collaborate with each other in the designed network, under a certain consensus dynamics. The consensus constraint forces neighboring agents to cooperate with each other such that the disagreement between the time-domain actuation of the agents is driven to zero. The controller output of each agent is calculated using state-space variables; hence, optimal state estimators are designed first for the proposed observer-based consensus PPF control. The consensus controller is numerically investigated for a flexible smart structure, i.e., a thin aluminum beam that is clamped at its both ends. Results demonstrate that the consensus law successfully imposes synchronization between the independently controlled agents, as the disagreements between the decentralized PPF controller variables converge to zero in a short time. The new consensus PPF controller brings extra robustness to vibration suppression in smart structures, where malfunctions of an agent can be compensated for by referencing the neighboring agents’ performance. This is demonstrated in the results by comparing the new controller with former centralized PPF approach.

  16. The effect of positive and negative verbal feedback on surgical skills performance and motivation.

    PubMed

    Kannappan, Aarthy; Yip, Dana T; Lodhia, Nayna A; Morton, John; Lau, James N

    2012-01-01

    There is considerable effort and time invested in providing feedback to medical students and residents during their time in training. However, little effort has been made to measure the effects of positive and negative verbal feedback on skills performance and motivation to learn and practice. To probe these questions, first-year medical students (n = 25) were recruited to perform a peg transfer task on Fundamentals of Laparoscopic Surgery box trainers. Time to completion and number of errors were recorded. The students were then randomized to receive either positive or negative verbal feedback from an expert in the field of laparoscopic surgery. After this delivery of feedback, the students repeated the peg transfer task. Differences in performance pre- and post-feedback and also between the groups who received positive feedback (PF) vs negative feedback (NF) were analyzed. A survey was then completed by all the participants. Baseline task times were similar between groups (PF 209.3 seconds; NF 203 seconds, p = 0.58). The PF group averaged 1.83 first-time errors while the NF group 1 (p = 0.84). Post-feedback task times were significantly decreased for both groups (PF 159.75 seconds, p = 0.05; NF 132.08 seconds, p = 0.002). While the NF group demonstrated a greater improvement in mean time than the PF group, this was not statistically significant. Both groups also made fewer errors (PF 0.33 errors, p = 0.04; NF 0.38 errors, p = 0.23). When surveyed about their responses to standardized feedback scenarios, the students stated that both positive and negative verbal feedback could be potent stimulants for improved performance and motivation. Further research is required to better understand the effects of feedback on learner motivation and the interpersonal dynamic between mentors and their trainees. PMID:23111049

  17. Effects of endogenous proteins and microRNA target sequence in a positive feedback system.

    PubMed

    Kanda, Genki N; Togashi, Ryohei; Harashima, Hideyoshi; Kamiya, Hiroyuki

    2012-01-01

    A positive feedback system, using GAL4-vp16 (a fusion protein of yeast GAL4 and herpes simplex virus vp16) as an activator and firefly luciferase as a reporter, maintained luciferase expression for 7 d in mice. However, the luciferase expression decreased after 7 d, and this phenomenon could be caused by immunoreactions against these exogenous proteins. This hypothesis was examined by the following three strategies, designed to avoid the putative immunoreactions: (i) use of the endogenous secreted alkaline phosphatase (SEAP) protein as a reporter, (ii) replacement of vp16 with endogenous transcription factors, and (iii) insertion of the target sequence of microRNA expressed in cells of hematopoietic origin, to suppress GAL4-vp16 expression in antigen-presenting cells. The results obtained in this study suggested that silencing would be induced by mechanism(s) besides immunoreactions against reporter and activator proteins. PMID:22975505

  18. The MAGNUM survey: positive feedback in the nuclear region of NGC 5643 suggested by MUSE

    NASA Astrophysics Data System (ADS)

    Cresci, G.; Marconi, A.; Zibetti, S.; Risaliti, G.; Carniani, S.; Mannucci, F.; Gallazzi, A.; Maiolino, R.; Balmaverde, B.; Brusa, M.; Capetti, A.; Cicone, C.; Feruglio, C.; Bland-Hawthorn, J.; Nagao, T.; Oliva, E.; Salvato, M.; Sani, E.; Tozzi, P.; Urrutia, T.; Venturi, G.

    2015-10-01

    We study the ionization and kinematics of the ionized gas in the nuclear region of the barred Seyfert 2 galaxy NGC 5643 using MUSE integral field observations in the framework of the Measuring Active Galactic Nuclei Under MUSE Microscope (MAGNUM) survey. The data were used to identify regions with different ionization conditions and to map the gas density and the dust extinction. We find evidence for a double-sided ionization cone, possibly collimated by a dusty structure surrounding the nucleus. At the center of the ionization cone, outflowing ionized gas is revealed as a blueshifted, asymmetric wing of the [OIII] emission line, up to projected velocity v10 ~ -450 km s-1. The outflow is also seen as a diffuse, low-luminosity radio and X-ray jet, with similar extension. The outflowing material points in the direction of two clumps characterized by prominent line emission with spectra typical of HII regions, located at the edge of the dust lane of the bar. We propose that the star formation in the clumps is due to positive feedback induced by gas compression by the nuclear outflow, providing the first candidate for outflow-induced star formation in a Seyfert-like, radio-quiet AGN. This suggests that positive feedback may be a relevant mechanism in shaping the black hole-host galaxy coevolution. This work is based on observations made at the European Southern Observatory, Paranal, Chile (ESO program 60.A-9339).

  19. PKCδ maintains phenotypes of tumor initiating cells through cytokine-mediated autocrine loop with positive feedback.

    PubMed

    Kim, R-K; Suh, Y; Hwang, E; Yoo, K-C; Choi, K-S; An, S; Hwang, S-G; Kim, I-G; Kim, M-J; Lee, H-J; Lee, S-J

    2015-11-12

    The existence of tumor initiating cells (TICs) has been emerged as a good therapeutic target for treatment of glioblastoma that is the most aggressive brain tumor with poor prognosis. However, the molecular mechanisms that regulate the phenotypes of TICs still remain obscure. In this study, we found that PKCδ, among PKC isoforms, is preferentially activated in TICs and acts as a critical regulator for the maintenance of TICs in glioblastoma. By modulating the expression levels or activity of PKCδ, we demonstrated that PKCδ promotes self-renewal and tumorigenic potentials of TICs. Importantly, we found that the activation of PKCδ persists in TICs through an autocrine loop with positive feedback that was driven by PKCδ/STAT3/IL-23/JAK signaling axis. Moreover, for phenotypes of TICs, we showed that PKCδ activates AKT signaling component by phosphorylation specifically on Ser473. Taken together, we proposed that TICs regulate their own population in glioblastoma through an autocrine loop with positive feedback that is driven by PKCδ-dependent secretion of cytokines. PMID:25746003

  20. Positive and Negative Feedbacks and Free-Scale Pattern Distribution in Rural-Population Dynamics

    PubMed Central

    Alados, Concepción L.; Errea, Paz; Gartzia, Maite; Saiz, Hugo; Escós, Juan

    2014-01-01

    Depopulation of rural areas is a widespread phenomenon that has occurred in most industrialized countries, and has contributed significantly to a reduction in the productivity of agro-ecological resources. In this study, we identified the main trends in the dynamics of rural populations in the Central Pyrenees in the 20th C and early 21st C, and used density independent and density dependent models and identified the main factors that have influenced the dynamics. In addition, we investigated the change in the power law distribution of population size in those periods. Populations exhibited density-dependent positive feedback between 1960 and 2010, and a long-term positive correlation between agricultural activity and population size, which has resulted in a free-scale population distribution that has been disrupted by the collapse of the traditional agricultural society and by emigration to the industrialized cities. We concluded that complex socio-ecological systems that have strong feedback mechanisms can contribute to disruptive population collapses, which can be identified by changes in the pattern of population distribution. PMID:25474704

  1. Performance Feedback Processing Is Positively Biased As Predicted by Attribution Theory.

    PubMed

    Korn, Christoph W; Rosenblau, Gabriela; Rodriguez Buritica, Julia M; Heekeren, Hauke R

    2016-01-01

    A considerable literature on attribution theory has shown that healthy individuals exhibit a positivity bias when inferring the causes of evaluative feedback on their performance. They tend to attribute positive feedback internally (e.g., to their own abilities) but negative feedback externally (e.g., to environmental factors). However, all empirical demonstrations of this bias suffer from at least one of the three following drawbacks: First, participants directly judge explicit causes for their performance. Second, participants have to imagine events instead of experiencing them. Third, participants assess their performance only after receiving feedback and thus differences in baseline assessments cannot be excluded. It is therefore unclear whether the classically reported positivity bias generalizes to setups without these drawbacks. Here, we aimed at establishing the relevance of attributions for decision-making by showing an attribution-related positivity bias in a decision-making task. We developed a novel task, which allowed us to test how participants changed their evaluations in response to positive and negative feedback about performance. Specifically, we used videos of actors expressing different facial emotional expressions. Participants were first asked to evaluate the actors' credibility in expressing a particular emotion. After this initial rating, participants performed an emotion recognition task and did--or did not--receive feedback on their veridical performance. Finally, participants re-rated the actors' credibility, which provided a measure of how they changed their evaluations after feedback. Attribution theory predicts that participants change their evaluations of the actors' credibility toward the positive after receiving positive performance feedback and toward the negative after negative performance feedback. Our results were in line with this prediction. A control condition without feedback showed that correct or incorrect performance

  2. Performance Feedback Processing Is Positively Biased As Predicted by Attribution Theory

    PubMed Central

    Rodriguez Buritica, Julia M.; Heekeren, Hauke R.

    2016-01-01

    A considerable literature on attribution theory has shown that healthy individuals exhibit a positivity bias when inferring the causes of evaluative feedback on their performance. They tend to attribute positive feedback internally (e.g., to their own abilities) but negative feedback externally (e.g., to environmental factors). However, all empirical demonstrations of this bias suffer from at least one of the three following drawbacks: First, participants directly judge explicit causes for their performance. Second, participants have to imagine events instead of experiencing them. Third, participants assess their performance only after receiving feedback and thus differences in baseline assessments cannot be excluded. It is therefore unclear whether the classically reported positivity bias generalizes to setups without these drawbacks. Here, we aimed at establishing the relevance of attributions for decision-making by showing an attribution-related positivity bias in a decision-making task. We developed a novel task, which allowed us to test how participants changed their evaluations in response to positive and negative feedback about performance. Specifically, we used videos of actors expressing different facial emotional expressions. Participants were first asked to evaluate the actors’ credibility in expressing a particular emotion. After this initial rating, participants performed an emotion recognition task and did—or did not—receive feedback on their veridical performance. Finally, participants re-rated the actors’ credibility, which provided a measure of how they changed their evaluations after feedback. Attribution theory predicts that participants change their evaluations of the actors’ credibility toward the positive after receiving positive performance feedback and toward the negative after negative performance feedback. Our results were in line with this prediction. A control condition without feedback showed that correct or incorrect

  3. Age-related changes in deterministic learning from positive versus negative performance feedback.

    PubMed

    van de Vijver, Irene; Ridderinkhof, K Richard; de Wit, Sanne

    2015-01-01

    Feedback-based learning declines with age. Because older adults are generally biased toward positive information ("positivity effect"), learning from positive feedback may be less impaired than learning from negative outcomes. The literature documents mixed results, due possibly to variability between studies in task design. In the current series of studies, we investigated the influence of feedback valence on reinforcement learning in young and older adults. We used nonprobabilistic learning tasks, to more systematically study the effects of feedback magnitude, learning of stimulus-response (S-R) versus stimulus-outcome (S-O) associations, and working-memory capacity. In most experiments, older adults benefitted more from positive than negative feedback, but only with large feedback magnitudes. Positivity effects were pronounced for S-O learning, whereas S-R learning correlated with working-memory capacity in both age groups. These results underline the context dependence of positivity effects in learning and suggest that older adults focus on high gains when these are informative for behavior. PMID:25761598

  4. Increased atmospheric carbon dioxide and climate feedback mechanisms

    NASA Technical Reports Server (NTRS)

    Cess, R. D.

    1982-01-01

    As a consequence of fossil fuel burning, the atmospheric concentration of carbon dioxide has increased from 314 ppm in 1958, when detailed measurements of this quantity began, to a present value of 335 ppm; and it is estimated that during the next century, the CO2 concentration will double relative to its assumed preindustrial value of 290 ppm. Since CO2 is an infrared-active gas, increases in its atmospheric concentration would lead to a larger infrared opacity for the atmospheric which, by normal logic, would result in a warmer Earth. A number of modeling endeavors suggest a 2 to 4 C increase in global mean surface temperature with doubling of the CO2 concentration. But such estimates of CO2-induced warming are highly uncertain because of a lack of knowledge of climate feedback mechanisms. Interactive influences upon the solar and infrared opacities of the Earth-atmosphere system can either amplify or damp a climate-forcing mechanism such as increasing CO2. Climate feedback mechanisms discussed include climate sensitivity, cloudiness-radiation feedback, climate change predictions, and interactive atmospheric chemistry.

  5. 78 FR 13057 - Agency Information Collection Activities; Information Collection; IT Dashboard Feedback Mechanism

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-26

    ... ADMINISTRATION Agency Information Collection Activities; Information Collection; IT Dashboard Feedback Mechanism... to review and approve a previously approved information collection requirement regarding IT Dashboard... identified by Information Collection 3090- 0285, IT Dashboard Feedback Mechanism, by any of the...

  6. A DNA break- and phosphorylation-dependent positive feedback loop promotes immunoglobulin class-switch recombination.

    PubMed

    Vuong, Bao Q; Herrick-Reynolds, Kayleigh; Vaidyanathan, Bharat; Pucella, Joseph N; Ucher, Anna J; Donghia, Nina M; Gu, Xiwen; Nicolas, Laura; Nowak, Urszula; Rahman, Numa; Strout, Matthew P; Mills, Kevin D; Stavnezer, Janet; Chaudhuri, Jayanta

    2013-11-01

    The ability of activation-induced cytidine deaminase (AID) to efficiently mediate class-switch recombination (CSR) is dependent on its phosphorylation at Ser38; however, the trigger that induces AID phosphorylation and the mechanism by which phosphorylated AID drives CSR have not been elucidated. Here we found that phosphorylation of AID at Ser38 was induced by DNA breaks. Conversely, in the absence of AID phosphorylation, DNA breaks were not efficiently generated at switch (S) regions in the immunoglobulin heavy-chain locus (Igh), consistent with a failure of AID to interact with the endonuclease APE1. Additionally, deficiency in the DNA-damage sensor ATM impaired the phosphorylation of AID at Ser38 and the interaction of AID with APE1. Our results identify a positive feedback loop for the amplification of DNA breaks at S regions through the phosphorylation- and ATM-dependent interaction of AID with APE1. PMID:24097111

  7. Predation risk suppresses the positive feedback between size structure and cannibalism.

    PubMed

    Kishida, Osamu; Trussell, Geoffrey C; Ohno, Ayaka; Kuwano, Shinya; Ikawa, Takuya; Nishimura, Kinya

    2011-11-01

    1. Cannibalism can play a prominent role in the structuring and dynamics of ecological communities. Previous studies have emphasized the importance of size structure and density of cannibalistic species in shaping short- and long-term cannibalism dynamics, but our understanding of how predators influence cannibalism dynamics is limited. This is despite widespread evidence that many prey species exhibit behavioural and morphological adaptations in response to predation risk. 2. This study examined how the presence and absence of predation risk from larval dragonflies Aeshna nigroflava affected cannibalism dynamics in its prey larval salamanders Hynobius retardatus. 3. We found that feedback dynamics between size structure and cannibalism depended on whether dragonfly predation risk was present. In the absence of dragonfly risk cues, a positive feedback between salamander size structure and cannibalism through time occurred because most of the replicates in this treatment contained at least one salamander larvae having an enlarged gape (i.e. cannibal). In contrast, this feedback and the emergence of cannibalism were rarely observed in the presence of the dragonfly risk cues. Once salamander size divergence occurred, experimental reversals of the presence or absence of dragonfly risk cues did not alter existing cannibalism dynamics as the experiment progressed. Thus, the effects of risk on the mechanisms driving cannibalism dynamics likely operated during the early developmental period of the salamander larvae. 4. The effects of dragonfly predation risk on behavioural aspects of cannibalistic interactions among hatchlings may prohibit the initiation of dynamics between size structure and cannibalism. Our predation trials clearly showed that encounter rates among hatchlings and biting and ingestion rates of prospective prey by prospective cannibals were significantly lower in the presence vs. absence of dragonfly predation risk even though the size asymmetry

  8. Revealing a Two-Loop Transcriptional Feedback Mechanism in the Cyanobacterial Circadian Clock

    PubMed Central

    Hertel, Stefanie; Brettschneider, Christian; Axmann, Ilka M.

    2013-01-01

    Molecular genetic studies in the circadian model organism Synechococcus have revealed that the KaiC protein, the central component of the circadian clock in cyanobacteria, is involved in activation and repression of its own gene transcription. During 24 hours, KaiC hexamers run through different phospho-states during daytime. So far, it has remained unclear which phospho-state of KaiC promotes kaiBC expression and which opposes transcriptional activation. We systematically analyzed various combinations of positive and negative transcriptional feedback regulation by introducing a combined TTFL/PTO model consisting of our previous post-translational oscillator that considers all four phospho-states of KaiC and a transcriptional/translational feedback loop. Only a particular two-loop feedback mechanism out of 32 we have extensively tested is able to reproduce existing experimental observations, including the effects of knockout or overexpression of kai genes. Here, threonine and double phosphorylated KaiC hexamers activate and unphosphorylated KaiC hexamers suppress kaiBC transcription. Our model simulations suggest that the peak expression ratio of the positive and the negative component of kaiBC expression is the main factor for how the different two-loop feedback models respond to removal or to overexpression of kai genes. We discuss parallels between our proposed TTFL/PTO model and two-loop feedback structures found in the mammalian clock. PMID:23516349

  9. Computational Modeling of Morphogenesis Regulated by Mechanical Feedback

    PubMed Central

    Ramasubramanian, Ashok; Taber, Larry A.

    2008-01-01

    Mechanical forces cause changes in form during embryogenesis and likely play a role in regulating these changes. This paper explores the idea that changes in homeostatic tissue stress (target stress), possibly modulated by genes, drive some morphogenetic processes. Computational models are presented to illustrate how regional variations in target stress can cause a range of complex behaviors involving the bending of epithelia. These models include growth and cytoskeletal contraction regulated by stress-based mechanical feedback. All simulations were carried out using the commercial finite element code ABAQUS, with growth and contraction included by modifying the zero-stress state in the material constitutive relations. Results presented for bending of bilayered beams and invagination of cylindrical and spherical shells provide insight into some of the mechanical aspects that must be considered in studying morphogenetic mechanisms. PMID:17318485

  10. The FONT5 Bunch-by-Bunch Position and Angle Feedback System at ATF2

    NASA Astrophysics Data System (ADS)

    Apsimon, R. J.; Bett, D. R.; Burrows, P. N.; Christian, G. B.; Constance, B.; Davis, M. R.; Gerbershagen, A.; Perry, C.; Resta-Lopez, J.

    The FONT5 upstream beam-based feedback system at ATF2 is designed to correct the position and angle jitter at the entrance to the ATF2 final-focus system, and also to demonstrate a prototype intra-train feedback system for the International Linear Collider interaction point. We discuss the hardware, from stripline BPMs to kickers, and RF and digital signal processing, as well as presenting results from the latest beam tests at ATF2.

  11. On the Feed-back Mechanism of Chinese Stock Markets

    NASA Astrophysics Data System (ADS)

    Lu, Shu Quan; Ito, Takao; Zhang, Jianbo

    Feed-back models in the stock markets research imply an adjustment process toward investors' expectation for current information and past experiences. Error-correction and cointegration are often used to evaluate the long-run relation. The Efficient Capital Market Hypothesis, which had ignored the effect of the accumulation of information, cannot explain some anomalies such as bubbles and partial predictability in the stock markets. In order to investigate the feed-back mechanism and to determine an effective model, we use daily data of the stock index of two Chinese stock markets with the expectational model, which is one kind of geometric lag models. Tests and estimations of error-correction show that long-run equilibrium seems to be seldom achieved in Chinese stock markets. Our result clearly shows the common coefficient of expectations and fourth-order autoregressive disturbance exist in the two Chinese stock markets. Furthermore, we find the same coefficient of expectations has an autoregressive effect on disturbances in the two Chinese stock markets. Therefore the presence of such feed-back is also supported in Chinese stock markets.

  12. Positive Feedback Regulation of stgR Expression for Secondary Metabolism in Streptomyces coelicolor

    PubMed Central

    Mao, Xu-Ming; Sun, Zhi-Hao; Liang, Bi-Rong; Wang, Zhi-Bin; Feng, Wei-Hong; Huang, Fang-Liang

    2013-01-01

    LysR-type transcriptional regulators (LTTRs) compose a large family and are responsible for various physiological functions in bacteria, while little is understood about their regulatory mechanism on secondary metabolism in Streptomyces. Here we reported that StgR, a typical LTTR in Streptomyces coelicolor, was a negative regulator of undecylprodigiosin (Red) and γ-actinorhodin (Act) production in the early developmental phase of secondary metabolism by suppressing the expression of two pathway-specific regulator genes, redD and actII-orf4, respectively. Meanwhile, stgR expression was downregulated during secondary metabolism to remove its repressive effects on antibiotic production. Moreover, stgR expression was positively autoregulated by direct binding of StgR to its own promoter (stgRp), and the binding site adjacent to translation start codon was determined by a DNase I footprinting assay. Furthermore, the StgR-stgRp interaction could be destroyed by the antibiotic γ-actinorhodin produced from S. coelicolor. Thus, our results suggested a positive feedback regulatory mechanism of stgR expression and antibiotic production for the rapid and irreversible development of secondary metabolism in Streptomyces. PMID:23457252

  13. Experimental study on active vibration control using genetic algorithm-based system identification and optimized positive position feedback

    NASA Astrophysics Data System (ADS)

    Orszulik, Ryan R.; Shan, Jinjun

    2012-12-01

    A genetic algorithm is implemented to identify the transfer function of an experimental system consisting of a flexible manipulator with a collocated piezoelectric sensor/actuator pair. A multi-mode positive position feedback controller is then designed based upon the identified transfer function. To this end, the same iteratively implemented genetic algorithm is used to optimize all controller parameters by minimization of the closed loop H∞-norm. The designed controller is then applied for vibration suppression on the experimental system.

  14. Dynamics of the interlocked positive feedback loops explaining the robust epigenetic switching in Candida albicans.

    PubMed

    Sriram, K; Soliman, Sylvain; Fages, François

    2009-05-01

    The two element mutual activation and inhibitory positive feedback loops are a common motifs that occur in many biological systems in both isolated and interlocked form, as for example, in the cell division cycle and thymus differentiation in eukaryotes. The properties of three element interlocked positive feedback loops that embeds both mutual activation and inhibition are studied in depth for their bistable properties by performing bifurcation and stochastic simulations. Codimension one and two bifurcations reveal important properties like robustness to parameter variations and adaptability under various conditions by its ability to fine tune the threshold to a wide range of values and to maintain a wide bistable regime. Furthermore, we show that in the interlocked circuit, mutual inhibition controls the decision to switch from OFF to ON state, while mutual activation enforces the decision. This view is supported through a concrete biological example Candida albicans, a human fungal pathogen that can exist in two distinctive cell types; one in the default white state and the other in an opaque form. Stochastic switching between these two forms takes place due to the epigenetic alternation induced by the transcriptional regulators in the circuit, albeit without any rearrangement of the nuclear chromosomes. The transcriptional regulators constitute interlocked mutual activation and inhibition feedback circuits that provide adaptable threshold and wide bistable regime. These positive feedback loops are shown to be responsible for robust noise induced transitions without chattering, persistence of particular phenotypes for many generations and selective exhibition of one particular form of phenotype when mutated. Finally, we propose for synthetic biology constructs to use interlocked positive feedback loops instead of two element positive feedback loops because they are better controlled than isolated mutual activation and mutual inhibition feedback circuits. PMID

  15. Visual saliency computations: mechanisms, constraints, and the effect of feedback.

    PubMed

    Soltani, Alireza; Koch, Christof

    2010-09-22

    The primate visual system continuously selects spatial proscribed regions, features or objects for further processing. These selection mechanisms--collectively termed selective visual attention--are guided by intrinsic, bottom-up and by task-dependent, top-down signals. While much psychophysical research has shown that overt and covert attention is partially allocated based on saliency-driven exogenous signals, it is unclear how this is accomplished at the neuronal level. Recent electrophysiological experiments in monkeys point to the gradual emergence of saliency signals when ascending the dorsal visual stream and to the influence of top-down attention on these signals. To elucidate the neural mechanisms underlying these observations, we construct a biologically plausible network of spiking neurons to simulate the formation of saliency signals in different cortical areas. We find that saliency signals are rapidly generated through lateral excitation and inhibition in successive layers of neural populations selective to a single feature. These signals can be improved by feedback from a higher cortical area that represents a saliency map. In addition, we show how top-down attention can affect the saliency signals by disrupting this feedback through its action on the saliency map. While we find that saliency computations require dominant slow NMDA currents, the signal rapidly emerges from successive regions of the network. In conclusion, using a detailed spiking network model we find biophysical mechanisms and limitations of saliency computations which can be tested experimentally. PMID:20861387

  16. Hydrogeochemical zonation in intertidal salt marsh sediments: evidence of positive plant-soil feedback?

    NASA Astrophysics Data System (ADS)

    Moffett, K. B.; Dittmar, J.; Seyfferth, A.; Fendorf, S.; Gorelick, S.

    2012-12-01

    Surface and subsurface environments are linked by the biogeochemical activity in near-surface sediment and by the hydrological fluxes that mobilize its reagents and products. A particularly dynamic and interesting setting to study near-surface hydrogeochemistry is the intertidal zone. Here, the very strong tidal hydraulic forcing is often thought to dominate water and solute transport. However, we demonstrated the importance of two additional subsurface drivers: groundwater flow and plant root water uptake. A high-resolution, coupled surface water-groundwater model of an intertidal salt marsh in San Francisco Bay, CA showed that these three drivers vary over different spatial scales: tidal flooding varies over 10's of meters; groundwater flow varies over meters, particularly within channel banks; and plant root water uptake varies in 3D at the sub-meter scale. Expanding on this third driver, we investigated whether the spatial variations in soil-water-plant hydraulic interactions that occur due to vegetation zonation also cause distinct geochemical zonation in salt marsh sediment pore waters. The existence of such geochemical zonation was verified and mapped by detailed field observations of the chemical composition of sediments, pore waters, surface waters, and vegetation. The field data and the coupled hydrologic model were then further analyzed to evaluate potential causal mechanisms for the geochemical zonation, including testing the hypothesis that the vegetation affects pore water geochemistry via a positive feedback beneficial to itself. If further supported by future studies, this geochemical feedback may complement known physical ecosystem engineering mechanisms to help stabilize and organize intertidal wetlands.

  17. Stabilizing PID controllers for a single-link biomechanical model with position, velocity, and force feedback.

    PubMed

    Iqbal, Kamran; Roy, Anindo

    2004-12-01

    In this paper we address the problem of PID stabilization of a single-link inverted pendulum-based biomechanical model with force feedback, two levels of position and velocity feedback, and with delays in all the feedback loops. The novelty of the proposed model lies in its physiological relevance, whereby both small and medium latency sensory feedbacks from muscle spindle (MS), and force feedback from Golgi tendon organ (GTO) are included in the formulation. The biomechanical model also includes active and passive viscoelastic feedback from Hill-type muscle model and a second-order low-pass function for muscle activation. The central nervous system (CNS) regulation of postural movement is represented by a proportional-integral-derivative (PID) controller. Padé approximation of delay terms is employed to arrive at an overall rational transfer function of the biomechanical model. The Hermite-Biehler theorem is then used to derive stability results, leading to the existence of stabilizing PID controllers. An algorithm for selection of stabilizing feedback gains is developed using the linear matrix inequality (LMI) approach. PMID:15796343

  18. Positive tropical marine low-cloud cover feedback inferred from cloud-controlling factors

    NASA Astrophysics Data System (ADS)

    Qu, Xin; Hall, Alex; Klein, Stephen A.; DeAngelis, Anthony M.

    2015-09-01

    Differences in simulations of tropical marine low-cloud cover (LCC) feedback are sources of significant spread in temperature responses of climate models to anthropogenic forcing. Here we show that in models the feedback is mainly driven by three large-scale changes—a strengthening tropical inversion, increasing surface latent heat flux, and an increasing vertical moisture gradient. Variations in the LCC response to these changes alone account for most of the spread in model-projected 21st century LCC changes. A methodology is devised to constrain the LCC response observationally using sea surface temperature (SST) as a surrogate for the latent heat flux and moisture gradient. In models where the current climate's LCC sensitivities to inversion strength and SST variations are consistent with observed, LCC decreases systematically, which would increase absorption of solar radiation. These results support a positive LCC feedback. Correcting biases in the sensitivities will be an important step toward more credible simulation of cloud feedbacks.

  19. Control of cardiac alternans by mechanical and electrical feedback

    NASA Astrophysics Data System (ADS)

    Yapari, Felicia; Deshpande, Dipen; Belhamadia, Youssef; Dubljevic, Stevan

    2014-07-01

    A persistent alternation in the cardiac action potential duration has been linked to the onset of ventricular arrhythmia, which may lead to sudden cardiac death. A coupling between these cardiac alternans and the intracellular calcium dynamics has also been identified in previous studies. In this paper, the system of PDEs describing the small amplitude of alternans and the alternation of peak intracellular Ca2+ are stabilized by optimal boundary and spatially distributed actuation. A simulation study demonstrating the successful annihilation of both alternans on a one-dimensional cable of cardiac cells by utilizing the full-state feedback controller is presented. Complimentary to these studies, a three variable Nash-Panfilov model is used to investigate alternans annihilation via mechanical (or stretch) perturbations. The coupled model includes the active stress which defines the mechanical properties of the tissue and is utilized in the feedback algorithm as an independent input from the pacing based controller realization in alternans annihilation. Simulation studies of both control methods demonstrate that the proposed methods can successfully annihilate alternans in cables that are significantly longer than 1 cm, thus overcoming the limitations of earlier control efforts.

  20. Positive feedback and alternative stable states in inbreeding, cooperation, sex roles and other evolutionary processes

    PubMed Central

    Lehtonen, Jussi; Kokko, Hanna

    2012-01-01

    A large proportion of studies in systems science focus on processes involving a mixture of positive and negative feedbacks, which are also common themes in evolutionary ecology. Examples of negative feedback are density dependence (population regulation) and frequency-dependent selection (polymorphisms). Positive feedback, in turn, plays a role in Fisherian ‘runaway’ sexual selection, the evolution of cooperation, selfing and inbreeding tolerance under purging of deleterious alleles, and the evolution of sex differences in parental care. All these examples feature self-reinforcing processes where the increase in the value of a trait selects for further increases, sometimes via a coevolutionary feedback loop with another trait. Positive feedback often leads to alternative stable states (evolutionary endpoints), making the interpretation of evolutionary predictions challenging. Here, we discuss conceptual issues such as the relationship between self-reinforcing selection and disruptive selection. We also present an extension of a previous model on parental care, focusing on the relationship between the operational sex ratio and sexual selection, and the influence of this relationship on the evolution of biparental or uniparental care. PMID:22144384

  1. Coupled Positive and Negative Feedbacks Produce Diverse Gene Expression Patterns in Colonies

    PubMed Central

    Mitarai, Namiko; Jensen, Mogens Høgh

    2015-01-01

    ABSTRACT Formation of patterns is a common feature in the development of multicellular organism as well as of microbial communities. To investigate the formation of gene expression patterns in colonies, we build a mathematical model of two-dimensional colony growth, where cells carry a coupled positive-and-negative-feedback circuit. We demonstrate that the model can produce sectored, target (concentric), uniform, and scattered expression patterns of regulators, depending on gene expression dynamics and nutrient diffusion. We reconstructed the same regulatory structure in Escherichia coli cells and found gene expression patterns on the surface of colonies similar to the ones produced by the computer simulations. By comparing computer simulations and experimental results, we observed that very simple rules of gene expression can yield a spectrum of well-defined patterns in a growing colony. Our results suggest that variations of the protein content among cells lead to a high level of heterogeneity in colonies. Importance Formation of patterns is a common feature in the development of microbial communities. In this work, we show that a simple genetic circuit composed of a positive-feedback loop and a negative-feedback loop can produce diverse expression patterns in colonies. We obtained similar sets of gene expression patterns in the simulations and in the experiments. Because the combination of positive feedback and negative feedback is common in intracellular molecular networks, our results suggest that the protein content of cells is highly diversified in colonies. PMID:25852158

  2. Precise computer controlled positioning of robot end effectors using sensory feedback

    NASA Technical Reports Server (NTRS)

    Wang, J. C.; Tsai, J. S. H.; Mcinnis, B. C.; Shieh, L. S.

    1988-01-01

    A preliminary study of the combined position/force control using sensory feedback for a one-dimensional manipulator model, which may count for the spacecraft docking problem or to be extended to the multijoint robot manipulator problem, has been performed. The additional degrees of freedom introduced by the compliant force sensor is included in the system dynamics in the design of precise position control. State feedback based on pole placement method and with integral control is used to design the position controller. A simple constant gain force controller is used as an example to illustrate the dependence of the stability and steady-state accuracy of the overall position/force control on the design of the inner position controller. Supportive simulation results are also provided.

  3. A Positive Autoregulatory BDNF Feedback Loop via C/EBPβ Mediates Hippocampal Memory Consolidation

    PubMed Central

    Bambah-Mukku, Dhananjay; Travaglia, Alessio; Chen, Dillon Y.; Pollonini, Gabriella

    2014-01-01

    Little is known about the temporal progression and regulation of the mechanisms underlying memory consolidation. Brain-derived-neurotrophic-factor (BDNF) has been shown to mediate the maintenance of memory consolidation, but the mechanisms of this regulation remain unclear. Using inhibitory avoidance (IA) in rats, here we show that a hippocampal BDNF-positive autoregulatory feedback loop via CCAAT-enhancer binding protein β (C/EBPβ) is necessary to mediate memory consolidation. At training, a very rapid, learning-induced requirement of BDNF accompanied by rapid de novo translation controls the induction of a persistent activation of cAMP-response element binding-protein (CREB) and C/EBPβ expression. The latter, in turn, controls an increase in expression of bdnf exon IV transcripts and BDNF protein, both of which are necessary and, together with the initial BDNF requirement, mediate memory consolidation. The autoregulatory loop terminates by 48 h after training with decreased C/EBPβ and pCREB and increased methyl-CpG binding protein-2, histone-deacetylase-2, and switch-independent-3a binding at the bdnf exon IV promoter. PMID:25209292

  4. Positive And Negative Feedback Loops Coupled By Common Transcription Activator And Repressor

    NASA Astrophysics Data System (ADS)

    Sielewiesiuk, Jan; Łopaciuk, Agata

    2015-03-01

    Dynamical systems consisting of two interlocked loops with negative and positive feedback have been studied using the linear analysis of stability and numerical solutions. Conditions for saddle-node bifurcation were formulated in a general form. Conditions for Hopf bifurcations were found in a few symmetrical cases. Auto-oscillations, when they exist, are generated by the negative feedback repressive loop. This loop determines the frequency and amplitude of oscillations. The positive feedback loop of activation slightly modifies the oscillations. Oscillations are possible when the difference between Hilll's coefficients of the repression and activation is sufficiently high. The highly cooperative activation loop with a fast turnover slows down or even makes the oscillations impossible. The system under consideration can constitute a component of epigenetic or enzymatic regulation network.

  5. Observational and model evidence for positive low-level cloud feedback.

    PubMed

    Clement, Amy C; Burgman, Robert; Norris, Joel R

    2009-07-24

    Feedbacks involving low-level clouds remain a primary cause of uncertainty in global climate model projections. This issue was addressed by examining changes in low-level clouds over the Northeast Pacific in observations and climate models. Decadal fluctuations were identified in multiple, independent cloud data sets, and changes in cloud cover appeared to be linked to changes in both local temperature structure and large-scale circulation. This observational analysis further indicated that clouds act as a positive feedback in this region on decadal time scales. The observed relationships between cloud cover and regional meteorological conditions provide a more complete way of testing the realism of the cloud simulation in current-generation climate models. The only model that passed this test simulated a reduction in cloud cover over much of the Pacific when greenhouse gases were increased, providing modeling evidence for a positive low-level cloud feedback. PMID:19628865

  6. Confinement and diffusion modulate bistability and stochastic switching in a reaction network with positive feedback

    NASA Astrophysics Data System (ADS)

    Mlynarczyk, Paul J.; Pullen, Robert H.; Abel, Steven M.

    2016-01-01

    Positive feedback is a common feature in signal transduction networks and can lead to phenomena such as bistability and signal propagation by domain growth. Physical features of the cellular environment, such as spatial confinement and the mobility of proteins, play important but inadequately understood roles in shaping the behavior of signaling networks. Here, we use stochastic, spatially resolved kinetic Monte Carlo simulations to explore a positive feedback network as a function of system size, system shape, and mobility of molecules. We show that these physical properties can markedly alter characteristics of bistability and stochastic switching when compared with well-mixed simulations. Notably, systems of equal volume but different shapes can exhibit qualitatively different behaviors under otherwise identical conditions. We show that stochastic switching to a state maintained by positive feedback occurs by cluster formation and growth. Additionally, the frequency at which switching occurs depends nontrivially on the diffusion coefficient, which can promote or suppress switching relative to the well-mixed limit. Taken together, the results provide a framework for understanding how confinement and protein mobility influence emergent features of the positive feedback network by modulating molecular concentrations, diffusion-influenced rate parameters, and spatiotemporal correlations between molecules.

  7. Microcantilever Displacement Measurement Using a Mechanically Modulated Optical Feedback Interferometer.

    PubMed

    Azcona, Francisco J; Jha, Ajit; Yáñez, Carlos; Atashkhooei, Reza; Royo, Santiago

    2016-01-01

    Microcantilever motion detection is a useful tool for the characterization of the physical, chemical and biological properties of materials. In the past, different approaches have been proposed and tested to enhance the behavior, size and simplicity of microcantilever motion detectors. In this paper, a new approach to measure microcantilever motion with nanometric resolution is presented. The proposed approach is based on the concept of mechanically-modulated optical feedback interferometry, a technique that has shown displacement measurement capabilities well within the nanometric scale and that, due to its size, compactness and low cost, may be a suitable choice for measuring nanometric motions in cantilever-like sensors. It will be shown that the sensor, in its current state of development, is capable of following a cantilever sinusoidal trajectory at different sets of frequencies ranging up to 200 Hz and peak to peak amplitudes up to λ / 2 with experimental resolutions in the λ / 100 range. PMID:27367702

  8. Mechanical Feedback: From Stellar Wind Bubbles to Starbursts (Invited Talk)

    NASA Astrophysics Data System (ADS)

    Oey, M. S.; Clarke, C. J.; Massey, P.

    The current understanding of mechanical feedback is reviewed by evaluating the standard, adiabatic model for shell formation and evolution. This model is relevant to phenomena ranging from individual stellar-wind bubbles to galactic superwinds, forming the basis for our understanding of the multiphase ISM, IGM, and galactic evolutionary processes. Although significant discrepancies between the model and observation have been identified, to date there are none that require a fundamental revision. A variety of evidence, ranging over three orders of magnitude in spatial scale, is broadly consistent with the standard model. This includes kinematics of individual objects, observations of hot gas, the size distribution of HI shells, and outflow rates from starburst galaxies. However, some of the most pressing issues relating to shell evolution are still outstanding and obstruct efforts to resolve key questions like the fate of the hot gas.

  9. Microcantilever Displacement Measurement Using a Mechanically Modulated Optical Feedback Interferometer

    PubMed Central

    Azcona, Francisco J.; Jha, Ajit; Yáñez, Carlos; Atashkhooei, Reza; Royo, Santiago

    2016-01-01

    Microcantilever motion detection is a useful tool for the characterization of the physical, chemical and biological properties of materials. In the past, different approaches have been proposed and tested to enhance the behavior, size and simplicity of microcantilever motion detectors. In this paper, a new approach to measure microcantilever motion with nanometric resolution is presented. The proposed approach is based on the concept of mechanically-modulated optical feedback interferometry, a technique that has shown displacement measurement capabilities well within the nanometric scale and that, due to its size, compactness and low cost, may be a suitable choice for measuring nanometric motions in cantilever-like sensors. It will be shown that the sensor, in its current state of development, is capable of following a cantilever sinusoidal trajectory at different sets of frequencies ranging up to 200 Hz and peak to peak amplitudes up to λ/2 with experimental resolutions in the λ/100 range. PMID:27367702

  10. Feedback-Enhanced Parametric Squeezing of Mechanical Motion

    NASA Astrophysics Data System (ADS)

    Vinante, A.; Falferi, P.

    2013-11-01

    We present a single-quadrature feedback scheme able to overcome the conventional 3 dB limit on parametric squeezing. The method is experimentally demonstrated in a micromechanical system based on a cantilever with a magnetic tip. The cantilever is detected at low temperature by a SQUID susceptometer, while parametric pumping is obtained by modulating the magnetic field gradient at twice the cantilever frequency. A maximum squeezing of 11.5 dB and 11.3 dB is observed, respectively, in the response to a sinusoidal test signal and in the thermomechanical noise. So far, the maximum squeezing factor is limited only by the maximum achievable parametric modulation. The proposed technique might be used to squeeze one quadrature of a mechanical resonator below the quantum noise level, even without the need for a quantum limited detector.

  11. Quantum feedback cooling of a mechanical oscillator using variational measurements: tweaking Heisenberg’s microscope

    NASA Astrophysics Data System (ADS)

    Habibi, Hojat; Zeuthen, Emil; Ghanaatshoar, Majid; Hammerer, Klemens

    2016-08-01

    We revisit the problem of preparing a mechanical oscillator in the vicinity of its quantum-mechanical ground state by means of feedback cooling based on continuous optical detection of the oscillator position. In the parameter regime relevant to ground-state cooling, the optical back-action and imprecision noise set the bottleneck of achievable cooling and must be carefully balanced. This can be achieved by adapting the phase of the local oscillator in the homodyne detection realizing a so-called variational measurement. The trade-off between accurate position measurement and minimal disturbance can be understood in terms of Heisenberg’s microscope and becomes particularly relevant when the measurement and feedback processes happen to be fast within the quantum coherence time of the system to be cooled. This corresponds to the regime of large quantum cooperativity {C}{{q}}≳ 1, which was achieved in recent experiments on feedback cooling. Our method provides a simple path to further pushing the limits of current state-of-the-art experiments in quantum optomechanics.

  12. Can interactive educational technologies support the link between ultrasound theory and practice via feedback mechanisms?

    PubMed Central

    2014-01-01

    Linking theory to practice is an area of concern for ultrasound students, clinical mentors and academic staff. The link between theory and practice requires a robust clinical mentorship scheme in addition to careful curricula design considerations to improve student outcomes. The introduction of interactive technology in education provides ripe opportunity to improve feedback to students to support the link between theory and practice. A series of three interactive learning and teaching activities were designed and delivered to a PostGraduate Ultrasound cohort, after which, evaluation was performed to answer the research question: Which interactive technologies support the link between theory and practice through improved feedback mechanisms? An action research methodology was adopted involving an enquiry based literature review, planning, design and action process. Data were collected following action of three interactive teaching and learning sessions within the Medical Ultrasound cohort of 2013/2014 at Glasgow Caledonian University via a paper based questionnaire. A 100% response rate was achieved (n = 14). All three interactive learning and teaching sessions were considered with 100% highest point agreement to support the link between ultrasound theory and practice via feedback. Students found all three designed and facilitated sessions valuable and relevant to their learning, which in turn provided positive experiences which were perceived to support the link between theory and practice through feedback. These activities can be considered valuable in Postgraduate Ultrasound education. PMID:27433244

  13. The regulation of positive and negative social feedback: A psychophysiological study.

    PubMed

    Vanderhasselt, Marie-Anne; Remue, Jonathan; Ng, Kwun Kei; Mueller, Sven C; De Raedt, Rudi

    2015-09-01

    Everyday social evaluations are psychologically potent and trigger self-reflective thoughts and feelings. The present study sought to examine the psychophysiological impact of such evaluations using eye tracking, pupillometry, and heart-rate variability. Fifty-nine healthy adult volunteers received rigged social feedback (criticism and praise) based on their photograph. Gaze data were collected to investigate processes of attentional deployment/allocation toward the self or the evaluator expressing criticism or praise. Whereas voluntary attention was directed to evaluators who expressed praise, attention was drawn to one's own picture after criticism. Pupil dilation and heart-rate variability were larger in response to criticism as compared to praise, suggesting a flexible and adaptive emotion regulatory effort in response to social information that triggers an affective response. Altogether, healthy individuals recruited more regulatory resources to cope with negative (as compared to positive) social feedback, and this processing of social feedback was associated with adjustments in self-focused attention. PMID:25810280

  14. Positive feedback loop between cancer stem cells and angiogenesis in hepatocellular carcinoma.

    PubMed

    Yao, Hong; Liu, Nianli; Lin, Marie C; Zheng, Junnian

    2016-09-01

    Anti-angiogenesis-related therapies have become the standard care for patients with advanced hepatocellular carcinoma (HCC), as HCC is a highly vascularized solid tumor. Unfortunately, only modest and limited efficacies are observed. Emerging evidence have attributed to the limited efficacy to the presence of cancer stem cells (CSCs) in the tumor. CSCs predominantly drives angiogenesis via releasing proangiogenic factors and exosomes. They have the ability to resistant intratumoral hypoxia via autophagy or by directly forming the tubular structure to obtain blood. On the other hand, the vascular niche in tumor microenvironment also releases growth factors via juxtacrine and paracrine mechanisms to support the growth of CSCs and maintain its stemness features. This positive feedback loop between angiogenesis and CSCs exists in liver tumor microenvironment that is responsible for the development and poor prognosis of HCC. In this review, we summarize recent advances in our understanding of the crosstalks between angiogenesis and CSCs, and their interactions in liver tumor microenvironment and their purpose that an effective anti-angiogenic therapy should also target CSCs for HCC treatment. PMID:27108065

  15. Streptozotocin-induced diabetes blocks the positive feedback release of luteinizing hormone in the female rat.

    PubMed

    Kienast, S G; Fadden, C; Steger, R W

    1993-01-01

    The effects of streptozotocin-induced (STZ) diabetes on the release of gonadotropins was studied in female rats. In the first experiment, rats were ovariectomized and 2 days later were injected with STZ. Three weeks later rats were treated with estrogen and progesterone and blood samples were taken via intraatrial cannulae for luteinizing hormone (LH) assay. Afternoon surges of LH were seen in 4/5 control but 0/8 STZ rats. Pituitary responses to LH-releasing hormone in vitro did not differ. In the 2nd experiment, ovariectomized estrogen-primed rats were killed prior to and during a progesterone-induced LH surge. As in Experiment 1, STZ-treatment inhibited the LH surge but did not effect the afternoon rise in median eminence norepinephrine turnover which has previously been shown to be important in stimulating LH release. Turnover of norepinephrine in the anterior hypothalamus was depressed in the diabetic rats both prior to and during the expected time of the LH surge. Dopamine turnover was depressed in all three brain regions studied. It can be concluded that the positive feedback control of LH release is severely attenuated in diabetic rats but the mechanism explaining the loss is not clear. Diabetes-induced alterations in hypothalamic catecholamine metabolism may be involved but further work is needed to more carefully define these relationships. PMID:8221130

  16. Positive low cloud and dust feedbacks amplify tropical North Atlantic Multidecadal Oscillation

    NASA Astrophysics Data System (ADS)

    Yuan, Tianle; Oreopoulos, Lazaros; Zelinka, Mark; Yu, Hongbin; Norris, Joel R.; Chin, Mian; Platnick, Steven; Meyer, Kerry

    2016-02-01

    The Atlantic Multidecadal Oscillation (AMO) is characterized by a horseshoe pattern of sea surface temperature (SST) anomalies and has a wide range of climatic impacts. While the tropical arm of AMO is responsible for many of these impacts, it is either too weak or completely absent in many climate model simulations. Here we show, using both observational and model evidence, that the radiative effect of positive low cloud and dust feedbacks is strong enough to generate the tropical arm of AMO, with the low cloud feedback more dominant. The feedbacks can be understood in a consistent dynamical framework: weakened tropical trade wind speed in response to a warm middle latitude SST anomaly reduces dust loading and low cloud fraction over the tropical Atlantic, which warms the tropical North Atlantic SST. Together they contribute to the appearance of the tropical arm of AMO. Most current climate models miss both the critical wind speed response and two positive feedbacks though realistic simulations of them may be essential for many climatic studies related to the AMO.

  17. On the feedback mechanism in supersonic cavity flows

    NASA Astrophysics Data System (ADS)

    Li, Weipeng; Nonomura, Taku; Fujii, Kozo

    2013-05-01

    Self-sustained oscillations in supersonic cavity flows are investigated by implicit large-eddy simulations of a supersonic flow (M∞ = 2.0, ReD = 105) past a three-dimensional rectangular cavity with length-to-depth ratio of 2. Both turbulent and laminar inflows are considered, and a variation of boundary-layer thickness in the turbulent inflow case is conducted. An additional simulation of turbulent free shear layer is also performed to illustrate the relationship between shedding vortices and acoustic excitations. Feedback mechanism is identified as the dominant mechanism driving the self-sustained oscillations in supersonic open cavity flows, regardless of the upstream turbulent state and the boundary-layer thickness. The generation of discrete vortices in the cavity shear layer is shown to be highly associated with acoustic excitations rather than natural instabilities of the cavity shear layer. Simulation results support that the primary noise source arises from the successive passage of large-scale vortices over the cavity trailing edge. The effects of upstream boundary layer on the shear-layer characteristics and acoustic fields will also be discussed.

  18. Positive feedback regulation of type I interferon by the interferon-stimulated gene STING

    PubMed Central

    Ma, Feng; Li, Bing; Yu, Yongxin; Iyer, Shankar S; Sun, Mingyu; Cheng, Genhong

    2015-01-01

    Stimulator of interferon genes (STING) is an important regulator of the innate immune response to cytoplasmic DNA. However, regulation of STING itself is largely unknown. Here, we show that STING transcription is induced by innate immune activators, such as cyclic dinucleotides (CDNs), through an IFNAR1- and STAT1-dependent pathway. We also identify a STAT1 binding site in the STING promoter that contributes to the activation of STING transcription. Furthermore, we show that induction of STING mediates the positive feedback regulation of CDN-triggered IFN-I. Thus, our study demonstrates that STING is an interferon-stimulated gene (ISG) and its induction is crucial for the IFN-I positive feedback loop. PMID:25572843

  19. Single screw interrupted thread positive displacement mechanism

    NASA Astrophysics Data System (ADS)

    Boblitt, Wayne W.

    1992-07-01

    A single screw positive displacement compressor mechanism employing shallow gate rotor tooth penetration of the main rotor for purposes of reducing internal leakage and consequent compressor inefficiencies is presented. The invention is provided with an interrupted main rotor thread for purposes of insuring multiple gate rotor teeth meshing with the drive portion of the main rotor thread, thereby reducing gate rotor tooth flank loads in the compressor section of the device. Provision is also made for main rotor thread baffling between the main rotor chamber section and the mechanism inlet.

  20. Eliminating the possibility at Chernobyl 4 of recriticality with positive feedback

    SciTech Connect

    Bowman, C.D.

    1996-04-29

    We have recently published an article in which we discuss means by which plutonium and other fissile material stored underground could reach criticality with positive feedback and therefore explosive potential. The Chernobyl rubble involving hundreds of tons of material is similar in some respects to the systems analyzed in the paper, and the practices there to control criticality may well increase the probability of a second event at Chernobyl 4. This paper explores the Chernobyl situation and remedial actions are recommended.

  1. Neural mechanisms underlying auditory feedback control of speech

    PubMed Central

    Reilly, Kevin J.; Guenther, Frank H.

    2013-01-01

    The neural substrates underlying auditory feedback control of speech were investigated using a combination of functional magnetic resonance imaging (fMRI) and computational modeling. Neural responses were measured while subjects spoke monosyllabic words under two conditions: (i) normal auditory feedback of their speech, and (ii) auditory feedback in which the first formant frequency of their speech was unexpectedly shifted in real time. Acoustic measurements showed compensation to the shift within approximately 135 ms of onset. Neuroimaging revealed increased activity in bilateral superior temporal cortex during shifted feedback, indicative of neurons coding mismatches between expected and actual auditory signals, as well as right prefrontal and Rolandic cortical activity. Structural equation modeling revealed increased influence of bilateral auditory cortical areas on right frontal areas during shifted speech, indicating that projections from auditory error cells in posterior superior temporal cortex to motor correction cells in right frontal cortex mediate auditory feedback control of speech. PMID:18035557

  2. Successful implementation of a guideline by peer comparisons, education, and positive physician feedback.

    PubMed

    Wigder, H N; Cohan Ballis, S F; Lazar, L; Urgo, R; Dunn, B H

    1999-01-01

    The objective of this study was to determine if peer comparisons, an educational intervention, and positive physician feedback would decrease ordering of knee X-ray studies. We prospectively studied the ordering of knee X-ray studies for patients presenting with knee injuries before and after an educational program to encourage use of the Ottawa decision rule for knee radiography. Physicians were able to privately compare their individual baseline X-ray utilization data with that of their colleagues. Although acceptance of the rule was voluntary, both oral and written feedback encouraged consideration of the rule in clinical decision-making. The percentage of knee injury patients who received X-ray studies, as well as the Percentage Abnormal Results (PAR, defined as the percentage of X-ray studies demonstrating a fracture or effusion), were calculated before and after the educational meeting. Results of the study showed that the percentage of patients presenting with knee injuries who received X-ray studies decreased 23%. In addition, the PAR increased 58.4% between the two study periods. In conclusion, physician behavior can be altered positively with reinforcement. Peer comparisons, education, and positive physician feedback decreased test ordering by physicians even without mandating use of a protocol. PAR is a useful outcome measure to track physician utilization. PMID:10499693

  3. Folding with thermal-mechanical feedback: A reply

    NASA Astrophysics Data System (ADS)

    Hobbs, Bruce E.; Regenauer-Lieb, Klaus; Ord, Alison

    2009-07-01

    A unified theory of deformation at all scales is outlined. Processes operating during deformation and metamorphism can be coupled in the form of reaction-diffusion equations. Solutions to these equations depend on the specific processes that dominate the dissipation of energy. Hobbs et al. (2008) is concerned with a scale where deformation and conduction of heat dominate and this corresponds to the regional scale. Other papers present results for other length and time scales. Boudinage develops through these processes in materials where the strict Biot theory predicts no boudinage. The strict Biot theory is applicable only at the instant of instability and provides no information on the subsequent growth of the folds. Analytical results for growth to large amplitudes show that only one wavelength develops and not a spectrum of wavelengths as proposed by Treagus and Hudleston (in press) and others. The wavelength to thickness ratio that finally develops is strongly dependent on boundary conditions and so such ratios tell us nothing about the conditions of folding unless these boundary conditions are known. The processes involved in folding with thermal-mechanical feedback are identical for single- and multi-layer systems so that it requires little space to expand the discussion to multi-layers.

  4. CGILS: Results from the First Phase of an International Project to Understand the Physical Mechanisms of Low Cloud Feedbacks in Single Column Models

    NASA Technical Reports Server (NTRS)

    Zhang, Minghua; Bretherton, Christopher S.; Blossey, Peter N.; Austin, Phillip H.; Bacmeister, Julio T.; Bony, Sandrine; Brient, Florent; Cheedela, Suvarchal K.; Cheng, Anning; DelGenio, Anthony; DeRoode, Stephan R.; Endo, Satoshi; Franklin, Charmaine N.; Oolaz, Jean-Christophe; Hannay, Cecile; Heus, Thijs; Isotta, Francesco Alessandro; Dufresne, Jean-Louis; Kang, In-Sik; Kawai, Hideaki; Kiehler, Martin; Larson, Vincent E.; Liu, Yangang; Lock, Adrian P.; Lohmann, Ulrike; Molod, Andrea M.; Suarez, Max J.

    2013-01-01

    1] CGILS-the CFMIP-GASS Intercomparison of Large Eddy Models (LESs) and single column models (SCMs)-investigates the mechanisms of cloud feedback in SCMs and LESs under idealized climate change perturbation. This paper describes the CGILS results from 15 SCMs and 8 LES models. Three cloud regimes over the subtropical oceans are studied: shallow cumulus, cumulus under stratocumulus, and well-mixed coastal stratus/stratocumulus. In the stratocumulus and coastal stratus regimes, SCMs without activated shallow convection generally simulated negative cloud feedbacks, while models with active shallow convection generally simulated positive cloud feedbacks. In the shallow cumulus alone regime, this relationship is less clear, likely due to the changes in cloud depth, lateral mixing, and precipitation or a combination of them. The majority of LES models simulated negative cloud feedback in the well-mixed coastal stratus/stratocumulus regime, and positive feedback in the shallow cumulus and stratocumulus regime. A general framework is provided to interpret SCM results: in a warmer climate, the moistening rate of the cloudy layer associated with the surface-based turbulence parameterization is enhanced; together with weaker large-scale subsidence, it causes negative cloud feedback. In contrast, in the warmer climate, the drying rate associated with the shallow convection scheme is enhanced. This causes positive cloud feedback. These mechanisms are summarized as the "NESTS" negative cloud feedback and the "SCOPE" positive cloud feedback (Negative feedback from Surface Turbulence under weaker Subsidence-Shallow Convection PositivE feedback) with the net cloud feedback depending on how the two opposing effects counteract each other. The LES results are consistent with these interpretations

  5. The Use of Feedback Mechanisms in Interpreting the Robustness of a Neoliberal Educational Assemblage

    ERIC Educational Resources Information Center

    Demerath, Peter; Mattheis, Allison

    2015-01-01

    This article demonstrates how using feedback mechanisms or "loops" as heuristic devices can help ethnographers explain the interior logic, robustness and contradictions within complex educational assemblages. After reviewing the use of feedback mechanisms in the natural and social sciences, particularly practice theory, the article…

  6. Vacuum ultraviolet light source utilizing rare gas scintillation amplification sustained by photon positive feedback

    NASA Technical Reports Server (NTRS)

    Aprile, Elena (Inventor); Chen, Danli (Inventor)

    1995-01-01

    A source of light in the vacuum ultraviolet (VUV) spectral region includes a reflective UV-sensitive photocathode supported in spaced parallel relationship with a mesh electrode within a rare gas at low pressure. A high positive potential applied to the mesh electrode creates an electric field which causes drifting of free electrons occurring between the electrodes and producing continuous VUV light output by electric field-driven scintillation amplification sustained by positive photon feedback mediated by photoemission from the photocathode. In one embodiment the lamp emits a narrow-band continuum peaked at 175 nm.

  7. Dynamics and Feedback Control of Plasma Equilibrium Position in a Tokamak.

    NASA Astrophysics Data System (ADS)

    Burenko, Oleg

    A brief history of the beginnings of nuclear fusion research involving toroidal closed-system magnetic plasma containment is presented. A tokamak machine is defined mathematically for the purposes of plasma equilibrium position perturbation analysis. The perturbation equations of a tokamak plasma equilibrium position are developed. Solution of the approximated perturbation equations is carried out. A unique, simple, and useful plasma displacement dynamics transfer function of a tokamak is developed. The dominant time constants of the dynamics transfer function are determined in a symbolic form. This symbolic form of the dynamics transfer function makes it possible to study the stability of a tokamak's plasma equilibrium position. Knowledge of the dynamics transfer function permits systematic syntheses of the required plasma displacement feedback control systems. The major parameters governing the plasma equilibrium position stability of a tokamak are shown to be (1) external magnetic field decay index, (2) transformer iron core effect, (3) plasma current, (4) radial rate-of-change inductance parameter, (5) vertical rate-of-change inductance parameter, and (6) vacuum vessel eddy-current time constant. An important and unique result is derived, showing that for a vacuum vessel eddy-current time constant exceeding a certain value the vertical plasma equilibrium position is stable, in spite of an intentional vertical instability design represented by a negative decay index. It is shown that a tokamak design having a theoretical set of positive decay index, negative radical rate-of-change inductance parameter, and positive vertical rate-of-change inductance parameter is expected to have a better plasma equilibrium position stability tolerance than a tokamak design having the same set with the signs reversed. The results of an actual hardware ISX-A tokamak plasma displacement feed-back control system design are presented. It is shown that a theoretical design computer

  8. Positive Feedback-Loop of Telomerase Reverse Transcriptase and 15-Lipoxygenase-2 Promotes Pulmonary Hypertension

    PubMed Central

    Shen, Tingting; Ma, Jun; Zhang, Lei; Yu, Xiufeng; Liu, Mengmeng; Hou, Yunlong; Wang, Yanyan; Ma, Cui; Li, Shuzhen; Zhu, Daling

    2013-01-01

    Objective Pulmonary hypertension (PH) is characterized with pulmonary vasoconstriction and vascular remodeling mediated by 15-lipoxygenase (15-LO)/15-hydroxyeicosatetraenoic acid (15-HETE) according to our previous studies. Meanwhile, telomerase reverse transcriptase (TERT) activity is highly correlated with vascular injury and remodeling, suggesting that TERT may be an essential determinant in the development of PH. The aim of this study was to determine the contribution and molecular mechanisms of TERT in the pathogenesis of PH. Approach and Results We measured the right ventricular systolic pressure (RVSP) and ventricular weight, analyzed morphometric change of the pulmonary vessels in the hypoxia or monocrotaline treated rats. Bromodeoxyuridine incorporation, transwell assay and flow cytometry in pulmonary smooth muscle cells were performed to investigate the roles and relationship of TERT and 15-LO/15-HETE in PH. We revealed that the expression of TERT was increased in pulmonary vasculature of patients with PH and in the monocrotaline or hypoxia rat model of PH. The up-regulation of TERT was associated with experimental elevated RVSP and pulmonary vascular remodeling. Coimmunoprecipitation experiments identified TERT as a novel interacting partner of 15-LO-2. TERT and 15-LO-2 augmented protein expression of each other. In addition, the proliferation, migration and cell-cycle transition from G0/G1 phase to S phase induced by hypoxia were inhibited by TERT knockdown, which were rescued by 15-HETE addition. Conclusions These results demonstrate that TERT regulates pulmonary vascular remodeling. TERT and 15-LO-2 form a positive feedback loop and together promote proliferation and migration of pulmonary artery smooth muscle cells, creating a self-amplifying circuit which propels pulmonary hypertension. PMID:24376652

  9. Effectiveness of chest compression feedback during cardiopulmonary resuscitation in lateral tilted and semirecumbent positions: a randomised controlled simulation study.

    PubMed

    Song, Y; Oh, J; Chee, Y; Cho, Y; Lee, S; Lim, T H

    2015-11-01

    Feedback devices have been shown to improve the quality of chest compression during cardiopulmonary resuscitation for patients in the supine position, but no studies have reported the effects of feedback devices on chest compression when the chest is tilted. Basic life support-trained providers were randomly assigned to administer chest compressions to a manikin in the supine, 30° left lateral tilt and 30° semirecumbent positions, with or without the aid of a feedback device incorporated into a smartphone. Thirty-six participants were studied. The feedback device did not affect the quality of chest compressions in the supine position, but improved aspects of performance in the tilted positions. In the lateral tilted position, the median (IQR [range]) chest compression rate was 99 (99-100 [96-117]) compressions.min(-1) with and 115 (95-128 [77-164]) compressions.min(-1) without feedback (p = 0.05), and the proportion of compressions of correct depth was 55 (0-96 [0-100])% with and 1 (0-30 [0-100])% without feedback (p = 0.03). In the semirecumbent position, the proportion of compressions of correct depth was 21 (0-87 [0-100])% with and 1 (0-26 [0-100])% without feedback (p = 0.05). Female participants applied chest compressions at a more accurate rate using the feedback device in the lateral tilted position but were unable to increase the chest compression depth, whereas male participants were able to increase the force of chest compression using the feedback device in the lateral tilted and semirecumbent positions. We conclude that a feedback device improves the application of chest compressions during simulated cardiopulmonary resuscitation when the chest is tilted. PMID:26349025

  10. Consecutive Positive Feedback Loops Create a Bistable Switch that Controls Preadipocyte-to-Adipocyte Conversion

    PubMed Central

    Park, Byung Ouk; Ahrends, Robert; Teruel, Mary N.

    2016-01-01

    SUMMARY Adipogenesis, or the conversion of proliferating preadipocytes into nondividing adipocytes, is an important part of the vertebrate weight-maintenance program. It is not yet understood how and when an irreversible transition occurs into a distinct state capable of accumulating lipid. Here, we use single-cell fluorescence imaging to show that an all-or-none switch is induced before lipid accumulation occurs. Conversion begins by glucocorticoid and cAMP signals raising C/EBPβ levels above a critical threshold, triggering three consecutive positive feedback loops: from PPARγ to C/EBPα, then to C/EBPβ, and last to the insulin receptor. Experiments and modeling show that these feedbacks create a robust, irreversible transition to a terminally differentiated state by rejecting short- and low-amplitude stimuli. After the differentiation switch is triggered, insulin controls fat accumulation in a graded fashion. Altogether, our study introduces a regulatory motif that locks cells in a differentiated state by engaging a sequence of positive feedback loops. PMID:23063366

  11. Rapid in situ X-ray position stabilization via extremum seeking feedback.

    PubMed

    Zohar, S; Venugopalan, N; Kissick, D; Becker, M; Xu, S; Makarov, O; Stepanov, S; Ogata, C; Sanishvili, R; Fischetti, R F

    2016-03-01

    X-ray beam stability is crucial for acquiring high-quality data at synchrotron beamline facilities. When the X-ray beam and defining apertures are of similar dimensions, small misalignments driven by position instabilities give rise to large intensity fluctuations. This problem is solved using extremum seeking feedback control (ESFC) for in situ vertical beam position stabilization. In this setup, the intensity spatial gradient required for ESFC is determined by phase comparison of intensity oscillations downstream from the sample with pre-existing vertical beam oscillations. This approach compensates for vertical position drift from all sources with position recovery times <6 s and intensity stability through a 5 µm aperture measured at 1.5% FWHM over a period of 8 hours. PMID:26917131

  12. Response to "The Iris Hypothesis: A Negative or Positive Cloud Feedback?"

    NASA Technical Reports Server (NTRS)

    Chou, Ming-Dah; Lindzen, Richard S.; Hou, Arthur Y.; Lau, William K. M. (Technical Monitor)

    2001-01-01

    Based on radiance measurements of Japan's Geostationary Meteorological Satellite, Lindzen et al. found that the high-level cloud cover averaged over the tropical western Pacific decreases with increasing sea surface temperature. They further found that the response of high-level clouds to the sea surface temperature had an effect of reducing the magnitude of climate change, which is referred as a negative climate feedback. Lin et al. reassessed the results found by Lindzen et al. by analyzing the radiation and clouds derived from the Tropical Rainfall Measuring Mission Clouds and the Earth's Radiant Energy System measurements. They found a weak positive feedback between high-level clouds and the surface temperature. We have found that the approach taken by Lin et al. to estimating the albedo and the outgoing longwave radiation is incorrect and that the inferred climate sensitivity is unreliable.

  13. Enhanced Positive Water Vapor Feedback Associated with Tropical Deep Convection: New Evidence from Aura MLS

    NASA Technical Reports Server (NTRS)

    Su, Hui; Read, William G.; Jiang, Jonathan H.; Waters, Joe W.; Wu, Dong L.; Fetzer, Eric J.

    2006-01-01

    Recent simultaneous observations of upper tropospheric (UT) water vapor and cloud ice from the Microwave Limb Sounder (MLS) on the Aura satellite provide new evidence for tropical convective influence on UT water vapor and its associated greenhouse effect. The observations show that UT water vapor increases as cloud ice water content increases. They also show that, when sea surface temperature (SST) exceeds approx.300 K, UT cloud ice associated with tropical deep convection increases sharply with increasing SST. The moistening of the upper troposphere by deep convection leads to an enhanced positive water vapor feedback, about 3 times that implied solely by thermodynamics. Over tropical oceans when SST greater than approx.300 K, the 'convective UT water vapor feedback' inferred from the MLS observations contributes approximately 65% of the sensitivity of the clear-sky greenhouse parameter to SST.

  14. Two-axis antenna positioning mechanism

    NASA Technical Reports Server (NTRS)

    Herald, Michelle; Wai, Leilani C.

    1994-01-01

    The two-axis antenna positioning mechanism (TAAPM) is used to position three Ku-band and one C-band spot antennas on the INTELSAT 7 (I-7) spacecraft, which is a commercial telecommunications satellite purchased and operated by INTELSAT, an international consortium. The first I-7 was successfully launched on 22 Oct. 1993 from French Guiana on an Ariane launch vehicle. The TAAPM's on the first I-7 satellite successfully completed their in-orbit functional testing. The TAAPM was an entirely new design for Space Systems/Loral. This paper will describe the spacecraft/system requirements and application of the TAAPM and present the technical findings of TAAPM qualification and protoflight testing.

  15. A MicroRNA-Mediated Positive Feedback Regulatory Loop of the NF-κB Pathway in Litopenaeus vannamei.

    PubMed

    Zuo, Hongliang; Yuan, Jia; Chen, Yonggui; Li, Sedong; Su, Ziqi; Wei, Erman; Li, Chaozheng; Weng, Shaoping; Xu, Xiaopeng; He, Jianguo

    2016-05-01

    In the evolutionarily conserved canonical NF-κB pathway, degradation of the NF-κB inhibitor IκB in the cytoplasmic NF-κB/IκB complex allows the liberated NF-κB to translocate into the nucleus to activate various target genes. The regulatory mechanism governing this process needs further investigation. In this study, a novel microRNA, temporarily named miR-1959, was first identified from an invertebrate Litopenaeus vannamei miR-1959 targets the 3'-untranslated region of the IκB homolog Cactus gene and reduces the protein level of Cactus in vivo, whereas the NF-κB homolog Dorsal directly binds the miR-1959 promoter to activate its transcription. Therefore, miR-1959 mediates a positive feedback regulatory loop, in that Dorsal activates miR-1959 expression, and in turn, miR-1959 inhibits the expression of Cactus, further leading to enhanced activation of Dorsal. Moreover, miR-1959 regulates the expression of many antimicrobial peptides in vivo and is involved in antibacterial immunity. To our knowledge, it is the first discovery of a microRNA-mediated feedback loop that directly regulates the NF-κB/IκB complex. This positive feedback loop could collaborate with the known NF-κB/IκB negative loop to generate a dynamic balance to regulate the activity of NF-κB, thus constituting an effective regulatory mechanism at the critical node of the NF-κB pathway. PMID:26994223

  16. Control of position and movement is simplified by combined muscle spindle and Golgi tendon organ feedback.

    PubMed

    Kistemaker, Dinant A; Van Soest, Arthur J Knoek; Wong, Jeremy D; Kurtzer, Isaac; Gribble, Paul L

    2013-02-01

    Whereas muscle spindles play a prominent role in current theories of human motor control, Golgi tendon organs (GTO) and their associated tendons are often neglected. This is surprising since there is ample evidence that both tendons and GTOs contribute importantly to neuromusculoskeletal dynamics. Using detailed musculoskeletal models, we provide evidence that simple feedback using muscle spindles alone results in very poor control of joint position and movement since muscle spindles cannot sense changes in tendon length that occur with changes in muscle force. We propose that a combination of spindle and GTO afferents can provide an estimate of muscle-tendon complex length, which can be effectively used for low-level feedback during both postural and movement tasks. The feasibility of the proposed scheme was tested using detailed musculoskeletal models of the human arm. Responses to transient and static perturbations were simulated using a 1-degree-of-freedom (DOF) model of the arm and showed that the combined feedback enabled the system to respond faster, reach steady state faster, and achieve smaller static position errors. Finally, we incorporated the proposed scheme in an optimally controlled 2-DOF model of the arm for fast point-to-point shoulder and elbow movements. Simulations showed that the proposed feedback could be easily incorporated in the optimal control framework without complicating the computation of the optimal control solution, yet greatly enhancing the system's response to perturbations. The theoretical analyses in this study might furthermore provide insight about the strong physiological couplings found between muscle spindle and GTO afferents in the human nervous system. PMID:23100138

  17. Positive Feedback between Mycorrhizal Fungi and Plants Influences Plant Invasion Success and Resistance to Invasion

    PubMed Central

    Zhang, Qian; Yang, Ruyi; Tang, Jianjun; Yang, Haishui; Hu, Shuijin; Chen, Xin

    2010-01-01

    Negative or positive feedback between arbuscular mycorrhizal fungi (AMF) and host plants can contribute to plant species interactions, but how this feedback affects plant invasion or resistance to invasion is not well known. Here we tested how alterations in AMF community induced by an invasive plant species generate feedback to the invasive plant itself and affect subsequent interactions between the invasive species and its native neighbors. We first examined the effects of the invasive forb Solidago canadensis L. on AMF communities comprising five different AMF species. We then examined the effects of the altered AMF community on mutualisms formed with the native legume forb species Kummerowia striata (Thunb.) Schindl. and on the interaction between the invasive and native plants. The host preferences of the five AMF were also assessed to test whether the AMF form preferred mutualistic relations with the invasive and/or the native species. We found that S. canadensis altered AMF spore composition by increasing one AMF species (Glomus geosporum) while reducing Glomus mosseae, which is the dominant species in the field. The host preference test showed that S. canadensis had promoted the abundance of AMF species (G. geosporum) that most promoted its own growth. As a consequence, the altered AMF community enhanced the competitiveness of invasive S. canadensis at the expense of K. striata. Our results demonstrate that the invasive S. canadensis alters soil AMF community composition because of fungal-host preference. This change in the composition of the AMF community generates positive feedback to the invasive S. canadensis itself and decreases AM associations with native K. striata, thereby making the native K. striata less dominant. PMID:20808770

  18. MECHANISMS OF CARBON MONOXIDE ATTENUATION OF TUBULOGLOMERULAR FEEDBACK (TGF)

    PubMed Central

    Ren, YiLin; D’Ambrosio, Martin A.; Wang, Hong; Falck, John R.; Peterson, Edward L.; Garvin, Jeffrey L.; Carretero, Oscar A.

    2012-01-01

    Carbon monoxide (CO) is a physiological messenger with diverse functions in the kidney, including controlling afferent arteriole (Af-Art) tone both directly and via tubuloglomerular feedback (TGF). We have reported that CO attenuates TGF, but the mechanisms underlying this effect remain unknown. We hypothesized that CO, acting via cGMP, cGMP-dependent protein kinase (PKG), and cGMP-stimulated phosphodiesterase-2 (PDE2), reduces cAMP in the macula densa, leading to TGF attenuation. In vitro, microdissected rabbit Af-Arts and their attached macula densa were simultaneously perfused. TGF was measured as the decrease in Af-Art diameter elicited by switching macula densa NaCl from 10 to 80 mM. Adding a CO-releasing molecule (CORM-3, 5×10−5mol/L) to the macula densa blunted TGF from 3.3±0.3 to 2.0±0.3 µm (P<0.001). The guanylate cyclase inhibitor LY-83583 (10−6mol/L) enhanced TGF (5.8±0.6 µm; P<0.001 vs. control) and prevented the effect of CORM-3 on TGF (LY-83583 + CORM-3, 5.5±0.3 µm). Similarly, the PKG inhibitor KT-5823 (2×10−6mol/L) enhanced TGF and prevented the effect of CORM-3 on TGF (KT-5823, 6.0±0.7 µm; KT-5823 + CORM-3, 5.9±0.8 µm). However, the PDE2 inhibitor BAY-60-7550 (10−6mol/L) did not prevent the effect of CORM-3 on TGF (BAY-60-7550, 4.07±0.31 µm; BAY-60-7550 + CORM-3, 1.84±0.31 µm, P<0.001). Finally, the degradation-resistant cAMP analog dibutyryl-cAMP (db-cAMP, 10−3mol/L) prevented the attenuation of TGF by CORM-3 (db-cAMP, 4.6±0.5 µm; db-cAMP + CORM-3, 5.0±0.6 µm). We conclude that CO attenuates TGF by reducing cAMP via a cGMP-dependent pathway mediated by PKG, rather than PDE2. Our results will lead to a better understanding of the mechanisms that control the renal microcirculation. PMID:22508834

  19. Mechanical implications of chimpanzee positional behavior.

    PubMed

    Hunt, K D

    1991-12-01

    Mechanical hypotheses concerning the function of chimpanzee anatomical specializations are examined in light of recent positional behavior data. Arm-hanging was the only common chimpanzee positional behavior that required full abduction of the humerus, and vertical climbing was the only distinctive chimpanzee positional behavior that required forceful retraction of the humerus and flexion of the elbow. Some elements of the chimpanzee anatomy, including an abductible humerus, a broad thorax, a cone-shaped torso, and a long, narrow scapula, are hypothesized to be a coadapted functional complex that reduces muscle action and structural fatigue during arm-hanging. Large muscles that retract the humerus (latissimus dorsi and probably sternocostal pectoralis major and posterior deltoid) and flex the elbow (biceps brachii, probably brachialis and brachioradialis) are argued to be adaptations to vertical climbing alone. A large ulnar excursion of the manus and long, curved metacarpals and phalanges are interpreted as adaptations to gripping vertical weight-bearing structures during vertical climbing and arm-hanging. A short torso, an iliac origin of the latissimus dorsi, and large muscles for arm-raising (caudal serratus, teres minor, cranial trapezius, and probably anterior deltoid and clavicular pectoralis major) are interpreted as adaptations to both climbing and unimanual suspension. PMID:1776659

  20. A Weak, Positive Feedback Between Sea Level and the Earth's Planetary Energy Budget

    NASA Astrophysics Data System (ADS)

    Marzeion, B.; Levermann, A.

    2014-12-01

    Increases in global mean temperature lead to increasing sea level mostly by loss of land ice mass and thermal expansion of the ocean. On millennial timescales, a warming of 5 K leads to flooding of about 1.6 % of Earth's current land surface, when taking into account the spatial distribution of relative sea-level rise caused by mass redistribution and isostatic rebound (Marzeion & Levermann, 2014). While there is great seasonal and spatial variability, the planetary albedo over the ocean is generally slightly lower than over land. We use millennial-scale, spatially explicit projections of relative sea-level rise, and the observed spatio-temporal distribution of planetary albedo and incident shortwave radiation, to determine the strength of the feedback between sea-level rise and the planetary energy budget. We find that the feedback is positive, but very weak. While the spatial pattern of sea-level rise is varying strongly with temperature, we find that the strength of the feedback is relatively independent of the temperature change, and around 0.8±0.1 %; i.e., an external forcing of 1 W/m2 will result in 1.008 W/m2 change of the energy balance.

  1. Valence-separated representation of reward prediction error in feedback-related negativity and positivity.

    PubMed

    Bai, Yu; Katahira, Kentaro; Ohira, Hideki

    2015-02-11

    Feedback-related negativity (FRN) is an event-related brain potential (ERP) component elicited by errors and negative outcomes. Previous studies proposed that FRN reflects the activity of a general error-processing system that incorporates reward prediction error (RPE). However, other studies reported inconsistent results on this issue - namely, that FRN only reflects the valence of feedback and that the magnitude of RPE is reflected by the other ERP component called P300. The present study focused on the relationship between the FRN amplitude and RPE. ERPs were recorded during a reversal learning task performed by the participants, and a computational model was used to estimate trial-by-trial RPEs, which we correlated with the ERPs. The results indicated that FRN and P300 reflected the magnitude of RPE in negative outcomes and positive outcomes, respectively. In addition, the correlation between RPE and the P300 amplitude was stronger than the correlation between RPE and the FRN amplitude. These differences in the correlation between ERP and RPE components may explain the inconsistent results reported by previous studies; the asymmetry in the correlations might make it difficult to detect the effect of the RPE magnitude on the FRN and makes it appear that the FRN only reflects the valence of feedback. PMID:25634316

  2. A positive feedback regulation of ISL-1 in DLBCL but not in pancreatic β-cells

    SciTech Connect

    Zhang, Qiao; Yang, Zhe; Wang, Weiping; Guo, Ting; Jia, Zhuqing; Ma, Kangtao; Zhou, Chunyan

    2014-07-04

    Highlights: • ISL-1 is highly expressed in human pancreatic β-cells and DLBCL. • ISL-1 accelerates the tumorigenesis of DLBCL in vivo. • c-Myc positively regulates ISL-1 expression in DLBCL but not in pancreatic β-cells. • ISL-1 and c-Myc forms an ISL-1/c-Myc transcriptional complex only in DLBCL. • Positive feedback regulation of ISL-1 does not exist in normal pancreatic β-cell. - Abstract: Insulin enhancer binding protein-1 (ISL-1), a LIM-homeodomain transcription factor, has been reported to play essential roles in promoting adult pancreatic β-cells proliferation. Recent studies indicate that ISL-1 may also involve in the occurrence of a variety of tumors. However, whether ISL-1 has any functional effect on tumorigenesis, and what are the differences on ISL-1 function in distinct conditions, are completely unknown. In this study, we found that ISL-1 was highly expressed in human pancreatic β-cells, as well as in diffuse large B cell lymphoma (DLBCL), but to a much less extent in other normal tissues or tumor specimens. Further study revealed that ISL-1 promoted the proliferation of pancreatic β-cells and DLBCL cells, and also accelerated the tumorigenesis of DLBCL in vivo. We also found that ISL-1 could activate c-Myc transcription not only in pancreatic β-cells but also in DLBCL cells. However, a cell-specific feedback regulation was detectable only in DLBCL cells. This auto-regulatory loop was established by the interaction of ISL-1 and c-Myc to form an ISL-1/c-Myc transcriptional complex, and synergistically to promote ISL-1 transcription through binding on the ISL-1 promoter. Taken together, our results demonstrate a positive feedback regulation of ISL-1 in DLBCL but not in pancreatic β-cells, which might result in the functional diversities of ISL-1 in different physiological and pathological processes.

  3. Positive genetic feedback governs cAMP spiral wave formation in Dictyostelium.

    PubMed Central

    Levine, H; Aranson, I; Tsimring, L; Truong, T V

    1996-01-01

    The aggregation stage of the life cycle of Dictyostelium discoideum is governed by the chemotactic response of individual amoebae to excitable waves of cAMP. We modeled this process through a recently introduced hybrid automata-continuum scheme and used computer simulation to unravel the role of specific components of this complex developmental process. Our results indicated an essential role for positive feedback between the cAMP signaling and the expression of the genes encoding the signal transduction and response machinery. PMID:8692824

  4. Grassland establishment under varying resource availability: a test of positive and negative feedback.

    PubMed

    Baer, Sara G; Blair, John M

    2008-07-01

    The traditional logic of carbon (C) and nitrogen (N) interactions in ecosystems predicts further increases or decreases in productivity (positive feedback) in response to high and low fertility in the soil, respectively; but the potential for development of feedback in ecosystems recovering from disturbance is less well understood. Furthermore, this logic has been challenged in grassland ecosystems where frequent fires or grazing may reduce the contribution of aboveground litter inputs to soil organic matter pools and nutrient supply for plant growth, relative to forest ecosystems. Further, if increases in plant productivity increase soil C content more than soil N content, negative feedback may result from increased microbial demand for N making less available for plant growth. We used a field experiment to test for feedback in an establishing grassland by comparing aboveground net primary productivity (ANPP) and belowground pools and fluxes of C and N in soil with enriched, ambient, and reduced N availability. For eight years annual N enrichment increased ANPP, root N, and root tissue quality, but root C:N ratios remained well above the threshold for net mineralization of N. There was no evidence that N enrichment increased root biomass, soil C or N accrual rates, or storage of C in total, microbial, or mineralizable pools within this time frame. However, the net nitrogen mineralization potential (NMP) rate was greater following eight years of N enrichment, and we attributed this to N saturation of the microbial biomass. Grassland developing under experimentally imposed N limitation through C addition to the soil exhibited ANPP, root biomass and quality, and net NMP rate similar to the ambient soil. Similarity in productivity and roots in the reduced and ambient N treatments was attributed to the potentially high nitrogen-use efficiency (NUE) of the dominant C4 grasses, and increasing cover of legumes over time in the C-amended soil. Thus, in a developing

  5. The Y-located gonadoblastoma gene TSPY amplifies its own expression through a positive feedback loop in prostate cancer cells

    SciTech Connect

    Kido, Tatsuo; Lau, Yun-Fai Chris

    2014-03-28

    Highlights: • Y-encoded proto-oncoprotein TSPY amplifies its expression level via a positive feedback loop. • TSPY binds to the chromatin/DNA at exon 1 of TSPY gene. • TSPY enhances the gene expression in a TSPY exon 1 sequence dependent manner. • The conserved SET/NAP-domain is essential for TSPY transactivation. • Insights on probable mechanisms on TSPY exacerbation on cancer development in men. - Abstract: The testis-specific protein Y-encoded (TSPY) is a repetitive gene located on the gonadoblastoma region of the Y chromosome, and has been considered to be the putative gene for this oncogenic locus on the male-only chromosome. It is expressed in spermatogonial cells and spermatocytes in normal human testis, but abundantly in gonadoblastoma, testicular germ cell tumors and a variety of somatic cancers, including melanoma, hepatocellular carcinoma and prostate cancer. Various studies suggest that TSPY accelerates cell proliferation and growth, and promotes tumorigenesis. In this report, we show that TSPY could bind directly to the chromatin/DNA at exon 1 of its own gene, and greatly enhance the transcriptional activities of the endogenous gene in the LNCaP prostate cancer cells. Domain mapping analyses of TSPY have localized the critical and sufficient domain to the SET/NAP-domain. These results suggest that TSPY could efficiently amplify its expression and oncogenic functions through a positive feedback loop, and contribute to the overall tumorigenic processes when it is expressed in various human cancers.

  6. Technology Enhanced Feedback Tools as a Knowledge Management Mechanism for Supporting Professional Growth and School Reform

    ERIC Educational Resources Information Center

    Bain, Alan; Swan, Gerry

    2011-01-01

    Attempts at school reform and improvement have experienced difficulty creating and implementing feedback systems that energize and sustain change efforts. If the call for reform at all levels of education is to be met, attention must be given to establishing effective feedback mechanisms in educational institutions as they embark on improvement…

  7. Movement goals and feedback and feedforward control mechanisms in speech production

    PubMed Central

    Perkell, Joseph S.

    2010-01-01

    Studies of speech motor control are described that support a theoretical framework in which fundamental control variables for phonemic movements are multi-dimensional regions in auditory and somatosensory spaces. Auditory feedback is used to acquire and maintain auditory goals and in the development and function of feedback and feedforward control mechanisms. Several lines of evidence support the idea that speakers with more acute sensory discrimination acquire more distinct goal regions and therefore produce speech sounds with greater contrast. Feedback modification findings indicate that fluently produced sound sequences are encoded as feedforward commands, and feedback control serves to correct mismatches between expected and produced sensory consequences. PMID:22661828

  8. Distributed mechanical feedback in arthropods and robots simplifies control of rapid running on challenging terrain.

    PubMed

    Spagna, J C; Goldman, D I; Lin, P-C; Koditschek, D E; Full, R J

    2007-03-01

    Terrestrial arthropods negotiate demanding terrain more effectively than any search-and-rescue robot. Slow, precise stepping using distributed neural feedback is one strategy for dealing with challenging terrain. Alternatively, arthropods could simplify control on demanding surfaces by rapid running that uses kinetic energy to bridge gaps between footholds. We demonstrate that this is achieved using distributed mechanical feedback, resulting from passive contacts along legs positioned by pre-programmed trajectories favorable to their attachment mechanisms. We used wire-mesh experimental surfaces to determine how a decrease in foothold probability affects speed and stability. Spiders and insects attained high running speeds on simulated terrain with 90% of the surface contact area removed. Cockroaches maintained high speeds even with their tarsi ablated, by generating horizontally oriented leg trajectories. Spiders with more vertically directed leg placement used leg spines, which resulted in more effective distributed contact by interlocking with asperities during leg extension, but collapsing during flexion, preventing entanglement. Ghost crabs, which naturally lack leg spines, showed increased mobility on wire mesh after the addition of artificial, collapsible spines. A bioinspired robot, RHex, was redesigned to maximize effective distributed leg contact, by changing leg orientation and adding directional spines. These changes improved RHex's agility on challenging surfaces without adding sensors or changing the control system. PMID:17671322

  9. Shifts in a single muscle's control potential of body dynamics are determined by mechanical feedback

    PubMed Central

    Sponberg, Simon; Libby, Thomas; Mullens, Chris H.; Full, Robert J.

    2011-01-01

    Muscles are multi-functional structures that interface neural and mechanical systems. Muscle work depends on a large multi-dimensional space of stimulus (neural) and strain (mechanical) parameters. In our companion paper, we rewrote activation to individual muscles in intact, behaving cockroaches (Blaberus discoidalis L.), revealing a specific muscle's potential to control body dynamics in different behaviours. Here, we use those results to provide the biologically relevant parameters for in situ work measurements. We test four hypotheses about how muscle function changes to provide mechanisms for the observed control responses. Under isometric conditions, a graded increase in muscle stress underlies its linear actuation during standing behaviours. Despite typically absorbing energy, this muscle can recruit two separate periods of positive work when controlling running. This functional change arises from mechanical feedback filtering a linear increase in neural activation into nonlinear work output. Changing activation phase again led to positive work recruitment, but at different times, consistent with the muscle's ability to also produce a turn. Changes in muscle work required considering the natural sequence of strides and separating swing and stance contributions of work. Both in vivo control potentials and in situ work loops were necessary to discover the neuromechanical coupling enabling control. PMID:21502130

  10. Efficient plant growth using automatic position-feedback laser light irradiation

    NASA Astrophysics Data System (ADS)

    Kakinoki, Yoshiaki; Kato, Yuya; Ogawa, Kosuke; Nakao, Akira; Okai, Zenshiro; Katsuyama, Toshio

    2013-05-01

    The plant growth based on the scanning laser beam is newly developed. Three semiconductor lasers with three primary colors, i.e., blue, green and red are used. Here, the laser scanned position is restricted only to the plant leaves, where the light illumination is needed. The feedback system based on the perspective projection is developed. The system consists of the automatic position correction from the camera image. The automatic image extraction of the leaf parts is also introduced. The electric power needed for this system is as small as 6.25% compared with the traditional white fluorescent lamp. Furthermore, experimental results show that the red-color laser light is particularly efficient for the growth of the radish sprouts.

  11. The Effect of Positive and Negative Feedback on Risk-Taking across Different Contexts

    PubMed Central

    Losecaat Vermeer, Annabel B.; Sanfey, Alan G.

    2015-01-01

    Preferences for risky choices have often been shown to be unstable and context-dependent. Though people generally avoid gambles with mixed outcomes, a phenomenon often attributed to loss aversion, contextual factors can impact this dramatically. For example, people typically prefer risky options after a financial loss, while generally choosing safer options after a monetary gain. However, it is unclear what exactly contributes to these preference shifts as a function of prior outcomes, as these gain/loss outcomes are usually confounded with participant performance, and therefore it is unclear whether these effects are driven purely by the monetary gains or losses, or rather by success or failure at the actual task. Here, we experimentally separated the effects of monetary gains/losses from performance success/failure prior to a standard risky choice. Participants performed a task in which they experienced contextual effects: 1) monetary gain or loss based directly on performance, 2) monetary gain or loss that was randomly awarded and was, crucially, independent from performance, and 3) success or failure feedback based on performance, but without any monetary incentive. Immediately following these positive/negative contexts, participants were presented with a gain-loss gamble that they had to decide to either play or pass. We found that risk preferences for identical sets of gambles were biased by positive and negative contexts containing monetary gains and losses, but not by contexts containing performance feedback. This data suggests that the observed framing effects are driven by aversion for monetary losses and not simply by the positive or negative valence of the context, or by potential moods resulting from positive or negative contexts. These results highlight the specific context dependence of risk preferences. PMID:26407298

  12. Theory and calculations of synchrotron instabilities and feedback-mechanism

    SciTech Connect

    Meijssen, T.E.M.

    1981-08-12

    The properties of the phenomenon synchrotron radiation are given with general theory on the basic processes and betatron and synchrotron oscillations. A more extended theoretical view at transverse instabilities and the influence of a damping feedback system are discussed. The longitudinal case is covered. For the calculations on the longitudinal case with M equally spaced pointbunches, with N electrons each, in the storage ring, the parasitic modes of the radio-frequency cavity were measured. A description of this is given. The values of damping rates of the longitudinal feedback system found, are as expected, but too low to damp the longitudinal instabilities calculated. This might be caused by the input data. The calculated growth rates are very sensitive to changes in frequency and width of the parasitic modes, which were measured under conditions differing slightly from the operating conditions.

  13. Sensitivity of feedback effects in CBMZ/MOSAIC chemical mechanism

    NASA Astrophysics Data System (ADS)

    San José, R.; Pérez, J. L.; Balzarini, A.; Baró, R.; Curci, G.; Forkel, R.; Galmarini, S.; Grell, G.; Hirtl, M.; Honzak, L.; Im, U.; Jiménez-Guerrero, P.; Langer, M.; Pirovano, G.; Tuccella, P.; Werhahn, J.; Žabkar, R.

    2015-08-01

    To investigate the impact of the aerosol effects on meteorological variables and pollutant concentrations two simulations with the WRF-Chem model have been performed over Europe for year 2010. We have performed a baseline simulation without any feedback effects and a second simulation including the direct as well as the indirect aerosol effect. The paper describes the full configuration of the model, the simulation design, special impacts and evaluation. Although low aerosol particle concentrations are detected, the inclusion of the feedback effects results in an increase of solar radiation at the surface over cloudy areas (North-West, including the Atlantic) and decrease over more sunny locations (South-East). Aerosol effects produce an increase of the water vapor and decrease the planet boundary layer height over the whole domain except in the Sahara area, where the maximum particle concentrations are detected. Significant ozone concentrations are found over the Mediterranean area. Simulated feedback effects between aerosol concentrations and meteorological variables and on pollutant distributions strongly depend on the aerosol concentrations and the clouds. Further investigations are necessary with higher aerosol particle concentrations. WRF-Chem variables are evaluated using available hourly observations in terms of performance statistics. Standardized observations from the ENSEMBLE system web-interface were used. The research was developed under the second phase of Air Quality Model Evaluation International Initiative (AQMEII). WRF-Chem demonstrates its capability in capturing temporal and spatial variations of the major meteorological variables and pollutants, except the wind speed over complex terrain. The wind speed bias may affect the accuracy in the chemical predictions (NO2, SO2). The analysis of the correlations between simulated data sets and observational data sets indicates that the simulation with aerosol effects performs slightly better. These

  14. Sahara Heat Low Perturbations and Water Vapor in the Sahel: A Positive Feedback System

    NASA Astrophysics Data System (ADS)

    Caughman, L.; Evan, A. T.

    2013-12-01

    It is necessary to understand the drivers and feedbacks of global desertification, motivated by the increasing need to improve global food production and to sustainably manage ecosystems in the context of climate change. Climate change and land dynamics are the perturbations that are major drivers of an ecosystem shift to a ';';desertified'' state. This shift is typically sustained by positive feedbacks, which stabilize the system in the new state. This research focuses on changes in precipitation resulting from land-atmosphere interactions and changes in vegetation cover. We concentrate on the Sahel region of Africa (a strip of land that is a transitional area between the Sahara desert to the North and the rain forest to the South). It is a dry land, semi arid environment and is a bistable ecosystem that can either be in the state of 'dry' or 'wet'. After an abnormally wet/high precipitation period in the 1950s the Sahel experienced terrible droughts and desertification which peaked in the 1980s. Since then, precipitation has gradually increased and a sinusoidal model has been shown run on a multi decadal cycle. Discrepancies in the data exist, however, and although the overall cycle has been modeled well, the large inter-annual fluctuations in precipitation have yet to be sufficiently modeled or explained. This research offers new evidence as to why such a phenomenon exists and attempts to attribute this behavior to a coupled land-atmosphere feedback system, linking together changes in vegetation cover and precipitation in the Sahel. Using the model output data from a high resolution Weather Research and Forecasting (WRF) model to look at Africa and compare the difference between perturbations and the mean, this research asserts that when the surface of the Saharan Heat Low (SHL) becomes extremely hot the pressure drops substantially. Subsequently, due to the West African Monsoon system, air rushes in from high-pressure areas, and pulls monsoon precipitation

  15. Finite-time stabilisation of simple mechanical systems using continuous feedback

    NASA Astrophysics Data System (ADS)

    Sanyal, Amit K.; Bohn, Jan

    2015-04-01

    Stabilisation of simple mechanical systems in finite time with continuous state feedback is considered here. The dynamics are represented by generalised (local) coordinates. A general methodology to construct control Lyapunov functions that are Hölder continuous and that can be used to show finite-time stability of the feedback controlled system, is presented. This construction also gives the feedback control law, and results in the feedback system being Hölder continuous as well. Unlike Lipschitz continuous feedback control systems, the feedback control scheme given here converges to the desired equilibrium in finite time. Moreover, unlike discontinuous and hybrid control schemes, the feedback control law does not lead to chattering in the presence of measurement noise, does not excite unmodelled high-frequency dynamics, and can be implemented with actuators that can only deliver continuous control inputs. The advantages of continuous finite-time stabilisation over continuous asymptotic stabilisation of mechanical systems, has been described in some prior research on finite-time stabilisation of the double integrator. The finite-time stabilisation scheme given here generalises this prior research to multiple degree-of-freedom mechanical systems. A numerical comparison is carried out through numerical simulations on two example systems that are representative of a broad class of simple mechanical systems.

  16. Functional characteristics of a double positive feedback loop coupled with autorepression

    NASA Astrophysics Data System (ADS)

    Banerjee, Subhasis; Bose, Indrani

    2008-12-01

    We study the functional characteristics of a two-gene motif consisting of a double positive feedback loop and an autoregulatory negative feedback loop. The motif appears in the gene regulatory network controlling the functional activity of pancreatic β-cells. The model exhibits bistability and hysteresis in appropriate parameter regions. The two stable steady states correspond to low (OFF state) and high (ON state) protein levels, respectively. Using a deterministic approach, we show that the region of bistability increases in extent when the copy number of one of the genes is reduced from 2 to 1. The negative feedback loop has the effect of reducing the size of the bistable region. Loss of a gene copy, brought about by mutations, hampers the normal functioning of the β-cells giving rise to the genetic disorder, maturity-onset diabetes of the young (MODY). The diabetic phenotype makes its appearance when a sizable fraction of the β-cells is in the OFF state. Using stochastic simulation techniques we show that, on reduction of the gene copy number, there is a transition from the monostable ON to the ON state in the bistable region of the parameter space. Fluctuations in the protein levels, arising due to the stochastic nature of gene expression, can give rise to transitions between the ON and OFF states. We show that as the strength of autorepression increases, the ON → OFF state transitions become less probable whereas the reverse transitions are more probable. The implications of the results in the context of the occurrence of MODY are pointed out.

  17. Spatial pattern formation of coastal vegetation in response to external gradients and positive feedbacks affecting soil porewater salinity: A model study

    USGS Publications Warehouse

    Jiang, J.; DeAngelis, D.L.; Smith, T. J., III; Teh, S.Y.; Koh, H. L.

    2012-01-01

    Coastal vegetation of South Florida typically comprises salinity-tolerant mangroves bordering salinity-intolerant hardwood hammocks and fresh water marshes. Two primary ecological factors appear to influence the maintenance of mangrove/hammock ecotones against changes that might occur due to disturbances. One of these is a gradient in one or more environmental factors. The other is the action of positive feedback mechanisms, in which each vegetation community influences its local environment to favor itself, reinforcing the boundary between communities. The relative contributions of these two factors, however, can be hard to discern. A spatially explicit individual-based model of vegetation, coupled with a model of soil hydrology and salinity dynamics is presented here to simulate mangrove/hammock ecotones in the coastal margin habitats of South Florida. The model simulation results indicate that an environmental gradient of salinity, caused by tidal flux, is the key factor separating vegetation communities, while positive feedback involving the different interaction of each vegetation type with the vadose zone salinity increases the sharpness of boundaries, and maintains the ecological resilience of mangrove/hammock ecotones against small disturbances. Investigation of effects of precipitation on positive feedback indicates that the dry season, with its low precipitation, is the period of strongest positive feedback. ?? 2011 Springer Science+Business Media B.V. (outside the USA).

  18. Construction of an Oscillator Gene Circuit by Negative and Positive Feedbacks.

    PubMed

    Shen, Shihui; Ma, Yushu; Ren, Yuhong; Wei, Dongzhi

    2016-01-01

    Synthetic oscillators are gene circuits in which the protein expression will change over time. The delay of transcription, translation, and protein folding is used to form this kind of behavior. Here, we tried to design a synthetic oscillator by a negative feedback combined with a positive feedback. With the mutant promoter PLacC repressed by LacIq and PLux activated by AHL-bound LuxR, two gene circuits, Os-LAA and Os-ASV, were constructed and introduced into LacI-deleted E. coli DH5α cells. When glucose was used as the carbon source, a low level of fluorescence was detected in the culture, and the bacteria with Os-ASV showed no oscillation, whereas a small portion of those carrying Os-LAA demonstrated oscillation behavior with a period of about 68.3 ± 20 min. When glycerol was used as the carbon source, bacteria with Os-ASV demonstrated high fluorescence value and oscillation behavior with the period of about 121 ± 21 min. PMID:26387818

  19. Better Bet-Hedging with coupled positive and negative feedback loops

    NASA Astrophysics Data System (ADS)

    Narula, Jatin; Igoshin, Oleg

    2011-03-01

    Bacteria use the phenotypic heterogeneity associated with bistable switches to distribute the risk of activating stress response strategies like sporulation and persistence. However bistable switches offer little control over the timing of phenotype switching and first passage times (FPT) for individual cells are found to be exponentially distributed. We show that a genetic circuit consisting of interlinked positive and negative feedback loops allows cells to control the timing of phenotypic switching. Using a mathematical model we find that in this system a stable high expression state and stable low expression limit cycle coexist and the FPT distribution for stochastic transitions between them shows multiple peaks at regular intervals. A multimodal FPT distribution allows cells to detect the persistence of stress and control the rate of phenotype transition of the population. We further show that extracellular signals from cell-cell communication that change the strength of the feedback loops can modulate the FPT distribution and allow cells even greater control in a bet-hedging strategy.

  20. A simple negative interaction in the positive transcriptional feedback of a single gene is sufficient to produce reliable oscillations.

    PubMed

    Miró-Bueno, Jesús M; Rodríguez-Patón, Alfonso

    2011-01-01

    Negative and positive transcriptional feedback loops are present in natural and synthetic genetic oscillators. A single gene with negative transcriptional feedback needs a time delay and sufficiently strong nonlinearity in the transmission of the feedback signal in order to produce biochemical rhythms. A single gene with only positive transcriptional feedback does not produce oscillations. Here, we demonstrate that this single-gene network in conjunction with a simple negative interaction can also easily produce rhythms. We examine a model comprised of two well-differentiated parts. The first is a positive feedback created by a protein that binds to the promoter of its own gene and activates the transcription. The second is a negative interaction in which a repressor molecule prevents this protein from binding to its promoter. A stochastic study shows that the system is robust to noise. A deterministic study identifies that the dynamics of the oscillator are mainly driven by two types of biomolecules: the protein, and the complex formed by the repressor and this protein. The main conclusion of this paper is that a simple and usual negative interaction, such as degradation, sequestration or inhibition, acting on the positive transcriptional feedback of a single gene is a sufficient condition to produce reliable oscillations. One gene is enough and the positive transcriptional feedback signal does not need to activate a second repressor gene. This means that at the genetic level an explicit negative feedback loop is not necessary. The model needs neither cooperative binding reactions nor the formation of protein multimers. Therefore, our findings could help to clarify the design principles of cellular clocks and constitute a new efficient tool for engineering synthetic genetic oscillators. PMID:22205920

  1. A Simple Negative Interaction in the Positive Transcriptional Feedback of a Single Gene Is Sufficient to Produce Reliable Oscillations

    PubMed Central

    Miró-Bueno, Jesús M.; Rodríguez-Patón, Alfonso

    2011-01-01

    Negative and positive transcriptional feedback loops are present in natural and synthetic genetic oscillators. A single gene with negative transcriptional feedback needs a time delay and sufficiently strong nonlinearity in the transmission of the feedback signal in order to produce biochemical rhythms. A single gene with only positive transcriptional feedback does not produce oscillations. Here, we demonstrate that this single-gene network in conjunction with a simple negative interaction can also easily produce rhythms. We examine a model comprised of two well-differentiated parts. The first is a positive feedback created by a protein that binds to the promoter of its own gene and activates the transcription. The second is a negative interaction in which a repressor molecule prevents this protein from binding to its promoter. A stochastic study shows that the system is robust to noise. A deterministic study identifies that the dynamics of the oscillator are mainly driven by two types of biomolecules: the protein, and the complex formed by the repressor and this protein. The main conclusion of this paper is that a simple and usual negative interaction, such as degradation, sequestration or inhibition, acting on the positive transcriptional feedback of a single gene is a sufficient condition to produce reliable oscillations. One gene is enough and the positive transcriptional feedback signal does not need to activate a second repressor gene. This means that at the genetic level an explicit negative feedback loop is not necessary. The model needs neither cooperative binding reactions nor the formation of protein multimers. Therefore, our findings could help to clarify the design principles of cellular clocks and constitute a new efficient tool for engineering synthetic genetic oscillators. PMID:22205920

  2. Protective role of Commensals against Clostridium difficile Infection via an IL-1β-Mediated Positive Feedback Loop

    PubMed Central

    Hasegawa, Mizuho; Kamada, Nobuhiko; Jiao, Yizu; Liu, Meng Zhen; Núñez, Gabriel; Inohara, Naohiro

    2013-01-01

    Clostridium difficile (Cd) is a Gram-positive obligate anaerobic pathogen that causes pseudomembranous colitis in antibiotic-treated individuals. Commensal bacteria are known to have a significant role in the intestinal accumulation of Cd after antibiotic treatment, but little is known about how they affect host immunity during Cd infection. Here we report that Cd infection results in translocation of commensals across the intestinal epithelial barrier that is critical for neutrophil recruitment through the induction of an IL-1β-mediated positive feedback loop. Mice lacking ASC, an essential mediator of IL-1β and IL-18 processing and secretion, were highly susceptible to Cd infection. ASC−/− mice exhibited enhanced translocation of commensals to multiple organs after Cd infection. Notably, ASC−/− mice exhibited impaired CXCL1 production and neutrophil influx into intestinal tissues in response to Cd infection. The impairment in neutrophil recruitment resulted in reduced production of IL-1β and CXCL1, but not IL-18. Importantly, translocated commensals were required for ASC/Nlrp3-dependent IL-1β secretion by neutrophils. Mice lacking IL-1β were deficient in inducing CXCL1 secretion, suggesting that IL-1β is the dominant inducer of ASC-mediated CXCL1 production during Cd infection. These results indicate that translocated commensals play a crucial role in CXCL1-dependent recruitment of neutrophils to the intestine through an IL-1β/NLRP3/ASC-mediated positive feedback mechanism that is important for host survival and clearance of translocated commensals during Cd infection. PMID:22888139

  3. Healthcare professional and patient codesign and validation of a mechanism for service users to feedback patient safety experiences following a care transfer: a qualitative study

    PubMed Central

    Scott, Jason; Heavey, Emily; Waring, Justin; Jones, Diana; Dawson, Pamela

    2016-01-01

    Objective To develop and validate a mechanism for patients to provide feedback on safety experiences following a care transfer between organisations. Design Qualitative study using participatory methods (codesign workshops) and cognitive interviews. Workshop data were analysed concurrently with participants, and cognitive interviews were thematically analysed using a deductive approach based on the developed feedback mechanism. Participants Expert patients (n=5) and healthcare professionals (n=11) were recruited purposively to develop the feedback mechanism in 2 workshops. Workshop 1 explored principles underpinning safety feedback mechanisms, and workshop 2 included the practical development of the feedback mechanism. Final design and content of the feedback mechanism (a safety survey) were verified by workshop participants, and cognitive interviews (n=28) were conducted with patients. Results Workshop participants identified that safety feedback mechanisms should be patient-centred, short and concise with clear signposting on how to complete, with an option to be anonymous and balanced between positive (safe) and negative (unsafe) experiences. The agreed feedback mechanism consisted of a survey split across 3 stages of the care transfer: departure, journey and arrival. Care across organisational boundaries was recognised as being complex, with healthcare professionals acknowledging the difficulty implementing changes that impact other organisations. Cognitive interview participants agreed the content of the survey was relevant but identified barriers to completion relating to the survey formatting and understanding of a care transfer. Conclusions Participatory, codesign principles helped overcome differences in understandings of safety in the complex setting of care transfers when developing a safety survey. Practical barriers to the survey's usability and acceptability to patients were identified, resulting in a modified survey design. Further research is

  4. Influence of visual feedback on successive control mechanisms in upright quiet stance in humans assessed by fractional Brownian motion modelling.

    PubMed

    Rougier, P

    1999-05-14

    An up-to-date way to model the centre of pressure (CP) trajectories may consist in using fractional Brownian motion (fBm). By doing so, one may note that standing still is in fact controlled by two separate and successive mechanisms. The point raised in this study concerns the nature of these control mechanisms and their level of interaction. Following this idea, visual feedback (VFB), which is known to affect postural control by significantly decreasing sway magnitudes, was used. Twelve healthy adults, instructed to stand as still as possible, were tested under this VFB protocol (via a PC screen). In order to model the CP trajectories as fBm, variograms (mean square distances, MSD, expressed as a function of increasing time intervals deltat) were bi-logarithmically plotted. The main visual effect of VFB on these variograms concerns longest latency scaling regimes which reveal less stochastic and consequently more accurate control (P < 0.05 and P < 0.01 for X and Y components, respectively). An increase in the MSD of the transition point, which corresponds to the switch between the two control mechanisms, is also noted (P < 0.05). Overall, evidence is provided from this data that long latency scaling regimes do operate through a feedback process. Interestingly, this improved determinism in feedback control in turn induces a similar effect on the control operating over the shortest deltat. Thus, by privileging a control strategy based on feedback mechanisms, VFB in turn would make the subjects quicker in their initial displacement in order to reach a position capable of initiating a feedback mechanism. PMID:10465697

  5. A Haptic Feedback Scheme to Accurately Position a Virtual Wrist Prosthesis Using a Three-Node Tactor Array.

    PubMed

    Erwin, Andrew; Sup, Frank C

    2015-01-01

    In this paper, a novel haptic feedback scheme, used for accurately positioning a 1DOF virtual wrist prosthesis through sensory substitution, is presented. The scheme employs a three-node tactor array and discretely and selectively modulates the stimulation frequency of each tactor to relay 11 discrete haptic stimuli to the user. Able-bodied participants were able to move the virtual wrist prosthesis via a surface electromyography based controller. The participants evaluated the feedback scheme without visual or audio feedback and relied solely on the haptic feedback alone to correctly position the hand. The scheme was evaluated through both normal (perpendicular) and shear (lateral) stimulations applied on the forearm. Normal stimulations were applied through a prototype device previously developed by the authors while shear stimulations were generated using an ubiquitous coin motor vibrotactor. Trials with no feedback served as a baseline to compare results within the study and to the literature. The results indicated that using normal and shear stimulations resulted in accurately positioning the virtual wrist, but were not significantly different. Using haptic feedback was substantially better than no feedback. The results found in this study are significant since the feedback scheme allows for using relatively few tactors to relay rich haptic information to the user and can be learned easily despite a relatively short amount of training. Additionally, the results are important for the haptic community since they contradict the common conception in the literature that normal stimulation is inferior to shear. From an ergonomic perspective normal stimulation has the potential to benefit upper limb amputees since it can operate at lower frequencies than shear-based vibrotactors while also generating less noise. Through further tuning of the novel haptic feedback scheme and normal stimulation device, a compact and comfortable sensory substitution device for upper

  6. A Haptic Feedback Scheme to Accurately Position a Virtual Wrist Prosthesis Using a Three-Node Tactor Array

    PubMed Central

    Erwin, Andrew; Sup, Frank C.

    2015-01-01

    In this paper, a novel haptic feedback scheme, used for accurately positioning a 1DOF virtual wrist prosthesis through sensory substitution, is presented. The scheme employs a three-node tactor array and discretely and selectively modulates the stimulation frequency of each tactor to relay 11 discrete haptic stimuli to the user. Able-bodied participants were able to move the virtual wrist prosthesis via a surface electromyography based controller. The participants evaluated the feedback scheme without visual or audio feedback and relied solely on the haptic feedback alone to correctly position the hand. The scheme was evaluated through both normal (perpendicular) and shear (lateral) stimulations applied on the forearm. Normal stimulations were applied through a prototype device previously developed by the authors while shear stimulations were generated using an ubiquitous coin motor vibrotactor. Trials with no feedback served as a baseline to compare results within the study and to the literature. The results indicated that using normal and shear stimulations resulted in accurately positioning the virtual wrist, but were not significantly different. Using haptic feedback was substantially better than no feedback. The results found in this study are significant since the feedback scheme allows for using relatively few tactors to relay rich haptic information to the user and can be learned easily despite a relatively short amount of training. Additionally, the results are important for the haptic community since they contradict the common conception in the literature that normal stimulation is inferior to shear. From an ergonomic perspective normal stimulation has the potential to benefit upper limb amputees since it can operate at lower frequencies than shear-based vibrotactors while also generating less noise. Through further tuning of the novel haptic feedback scheme and normal stimulation device, a compact and comfortable sensory substitution device for upper

  7. Output feedback integral control for nano-positioning using piezoelectric actuators

    NASA Astrophysics Data System (ADS)

    Shan, Jinjun; Yang, Liu; Li, Zhan

    2015-04-01

    This paper proposes a robust output feedback controller for a piezoelectrically actuated system with only position sensor. This considered piezoelectric actuator (PEA) system is subjected to model imperfection, creep nonlinearity, hysteresis nonlinearity and other external effects. The designed controller employs a second-order auxiliary system and a discontinuous uncertainty and disturbance estimation term to generate filtered error signals and to compensate for the model uncertainties and system disturbance, respectively. The global stability of the proposed controller is proved through Lyapunov-based stability analysis. The feasibility and effectiveness of the proposed control approach are verified experimentally using a PEA stage. Results demonstrate that both set-point and tracking control without/with external loads are realized with good performance and the PEA system with high-accuracy can be achieved. Moreover, the robustness of the controller is verified and analyzed through the sinusoidal tracking with external disturbance.

  8. Calculating the spontaneous magnetization and defining the Curie temperature using a positive-feedback model

    SciTech Connect

    Harrison, R. G.

    2014-01-21

    A positive-feedback mean-field modification of the classical Brillouin magnetization theory provides an explanation of the apparent persistence of the spontaneous magnetization beyond the conventional Curie temperature—the little understood “tail” phenomenon that occurs in many ferromagnetic materials. The classical theory is unable to resolve this apparent anomaly. The modified theory incorporates the temperature-dependent quantum-scale hysteretic and mesoscopic domain-scale anhysteretic magnetization processes and includes the effects of demagnetizing and exchange fields. It is found that the thermal behavior of the reversible and irreversible segments of the hysteresis loops, as predicted by the theory, is a key to the presence or absence of the “tails.” The theory, which permits arbitrary values of the quantum spin number J, generally provides a quantitative agreement with the thermal variations of both the spontaneous magnetization and the shape of the hysteresis loop.

  9. Optical boundary reconstruction of tokamak plasmas for feedback control of plasma position and shape

    SciTech Connect

    Hommen, G.; Baar, M. de; Nuij, P.; Steinbuch, M.; McArdle, G.; Akers, R.

    2010-11-15

    A new diagnostic is developed to reconstruct the plasma boundary using visible wavelength images. Exploiting the plasma's edge localized and toroidally symmetric emission profile, a new coordinate transform is presented to reconstruct the plasma boundary from a poloidal view image. The plasma boundary reconstruction is implemented in MATLAB and applied to camera images of Mega-Ampere Spherical Tokamak discharges. The optically reconstructed plasma boundaries are compared to magnetic reconstructions from the offline reconstruction code EFIT, showing very good qualitative and quantitative agreement. Average errors are within 2 cm and correlation is high. In the current software implementation, plasma boundary reconstruction from a single image takes 3 ms. The applicability and system requirements of the new optical boundary reconstruction, called OFIT, for use in both feedback control of plasma position and shape and in offline reconstruction tools are discussed.

  10. Preliminary results with saturable microchannel array plates. [featuring positive ion feedback elimination

    NASA Technical Reports Server (NTRS)

    Timothy, J. G.

    1974-01-01

    Microchannel array plates with a performance comparable to that of a conventional channel electron multiplier have been obtained for the first time. These array plates employ an angled electrostatic field to inhibit the feedback of positive ions within the microchannels. Saturated output pulse height distributions with modal gain values in excess of 10 million have been obtained and stable operation demonstrated over a range of ambient pressures from 0.0000001 to 0.00008 torr. However, a time-dependent reduction in the gain has been observed with these experimental plates because of the accumulation of charge on the insulating strips which are inserted in the wall of the microchannel to establish the angled electrostatic field.

  11. The impact of mechanical AGN feedback on the formation of massive early-type galaxies

    NASA Astrophysics Data System (ADS)

    Choi, Ena; Ostriker, Jeremiah P.; Naab, Thorsten; Oser, Ludwig; Moster, Benjamin P.

    2015-06-01

    We employ cosmological hydrodynamical simulations to investigate the effects of AGN feedback on the formation of massive galaxies with present-day stellar masses of M_stel= 8.8 × 10^{10}-6.0 × 10^{11} M_{⊙}. Using smoothed particle hydrodynamics simulations with a pressure-entropy formulation that allows an improved treatment of contact discontinuities and fluid mixing, we run three sets of simulations of 20 haloes with different AGN feedback models: (1) no feedback, (2) thermal feedback, and (3) mechanical and radiation feedback. We assume that seed black holes are present at early cosmic epochs at the centre of emerging dark matter haloes and trace their mass growth via gas accretion and mergers with other black holes. Both feedback models successfully recover the observed MBH-σ relation and black hole-to-stellar mass ratio for simulated central early-type galaxies. The baryonic conversion efficiencies are reduced by a factor of 2 compared to models without any AGN feedback at all halo masses. However, massive galaxies simulated with thermal AGN feedback show a factor of ˜10-100 higher X-ray luminosities than observed. The mechanical/radiation feedback model reproduces the observed correlation between X-ray luminosities and velocity dispersion, e.g. for galaxies with σ = 200 km s- 1, the X-ray luminosity is reduced from 1042 erg s- 1 to 1040 erg s- 1. It also efficiently suppresses late-time star formation, reducing the specific star formation rate from 10-10.5 yr- 1 to 10-14 yr- 1 on average and resulting in quiescent galaxies since z = 2, whereas the thermal feedback model shows higher late-time in situ star formation rates than observed.

  12. MiR-192-Mediated Positive Feedback Loop Controls the Robustness of Stress-Induced p53 Oscillations in Breast Cancer Cells

    PubMed Central

    Bleris, Leonidas; Ma, Lan

    2015-01-01

    The p53 tumor suppressor protein plays a critical role in cellular stress and cancer prevention. A number of post-transcriptional regulators, termed microRNAs, are closely connected with the p53-mediated cellular networks. While the molecular interactions among p53 and microRNAs have emerged, a systems-level understanding of the regulatory mechanism and the role of microRNAs-forming feedback loops with the p53 core remains elusive. Here we have identified from literature that there exist three classes of microRNA-mediated feedback loops revolving around p53, all with the nature of positive feedback coincidentally. To explore the relationship between the cellular performance of p53 with the microRNA feedback pathways, we developed a mathematical model of the core p53-MDM2 module coupled with three microRNA-mediated positive feedback loops involving miR-192, miR-34a, and miR-29a. Simulations and bifurcation analysis in relationship to extrinsic noise reproduce the oscillatory behavior of p53 under DNA damage in single cells, and notably show that specific microRNA abrogation can disrupt the wild-type cellular phenotype when the ubiquitous cell-to-cell variability is taken into account. To assess these in silico results we conducted microRNA-perturbation experiments in MCF7 breast cancer cells. Time-lapse microscopy of cell-population behavior in response to DNA double-strand breaks, together with image classification of single-cell phenotypes across a population, confirmed that the cellular p53 oscillations are compromised after miR-192 perturbations, matching well with the model predictions. Our study via modeling in combination with quantitative experiments provides new evidence on the role of microRNA-mediated positive feedback loops in conferring robustness to the system performance of stress-induced response of p53. PMID:26642352

  13. Feedback-free optical cavity with self-resonating mechanism

    NASA Astrophysics Data System (ADS)

    Uesugi, Y.; Hosaka, Y.; Honda, Y.; Kosuge, A.; Sakaue, K.; Omori, T.; Takahashi, T.; Urakawa, J.; Washio, M.

    2016-05-01

    We demonstrated the operation of a high finesse optical cavity without utilizing an active feedback system to stabilize the resonance. The effective finesse, which is a finesse including the overall system performance, of the cavity was measured to be 394 000 ± 10 000, and the laser power stored in the cavity was 2.52 ± 0.13 kW, which is approximately 187 000 times greater than the incident power to the cavity. The stored power was stabilized with a fluctuation of 1.7%, and we confirmed continuous cavity operation for more than two hours. This result has the potential to trigger an innovative evolution for applications that use optical resonant cavities such as compact photon sources with laser-Compton scattering or cavity enhanced absorption spectroscopy.

  14. Comparison of subtropical stratocumulus cloud feedback mechanisms in large-eddy simulations and observations (Invited)

    NASA Astrophysics Data System (ADS)

    Bretherton, C. S.; Blossey, P. N.

    2013-12-01

    Large-eddy simulation (LES) has uncovered competing mechanisms affecting the albedo response of subtropical cloud-topped boundary layers to idealized forcing perturbations representing different facets of global warming. Two stratocumulus-reducing mechanisms involve moist thermodynamic effects of warming on cloud-driven turbulence, and a more emissive free troposphere stifling cloud-top radiative cooling. Two cloud-enhancing effects involve increased inversion stability and reduced mean subsidence. Other effects such as changes in wind speed or free-tropospheric relative humidity may also induce regionally important cloud changes. LES simulations based on the CGILS intercomparison are used to quantify these effects in coupled and decoupled stratocumulus layers. They predict that the net result is a reduction of stratocumulus albedo (positive low cloud feedback) in a greenhouse climate, due mainly to the thermodynamic mechanism. This mechanism is explained in terms of temperature dependence of the moist thermodynamics underlying entrainment liquid-flux (ELF) adjustment, a rapid equilibration between the entrainment rate, the cloud-layer structure, and the turbulence within this layer. The latter mechanism may apply to a broad range of subtropical boundary layer cloud types, including shallow cumulus as well as stratocumulus. The LES-predicted response of shortwave cloud radiative effect (SWCRE) in subtropical stratocumulus regimes to these mechanisms are compared with some recent observational and GCM studies. The fractional changes of SWCRE are found to be qualitatively comparable between the LES and observations. This suggests that idealized LES studies are a useful guide to boundary-layer cloud response mechanisms to climate change, and such studies can help bridge between observations and GCMs.

  15. Self-Management of Patient Body Position, Pose, and Motion Using Wide-Field, Real-Time Optical Measurement Feedback: Results of a Volunteer Study

    SciTech Connect

    Parkhurst, James M.; Price, Gareth J.; Sharrock, Phil J.; Jackson, Andrew S.N.; Stratford, Julie; Moore, Christopher J.

    2013-12-01

    Purpose: We present the results of a clinical feasibility study, performed in 10 healthy volunteers undergoing a simulated treatment over 3 sessions, to investigate the use of a wide-field visual feedback technique intended to help patients control their pose while reducing motion during radiation therapy treatment. Methods and Materials: An optical surface sensor is used to capture wide-area measurements of a subject's body surface with visualizations of these data displayed back to them in real time. In this study we hypothesize that this active feedback mechanism will enable patients to control their motion and help them maintain their setup pose and position. A capability hierarchy of 3 different level-of-detail abstractions of the measured surface data is systematically compared. Results: Use of the device enabled volunteers to increase their conformance to a reference surface, as measured by decreased variability across their body surfaces. The use of visual feedback also enabled volunteers to reduce their respiratory motion amplitude to 1.7 ± 0.6 mm compared with 2.7 ± 1.4 mm without visual feedback. Conclusions: The use of live feedback of their optically measured body surfaces enabled a set of volunteers to better manage their pose and motion when compared with free breathing. The method is suitable to be taken forward to patient studies.

  16. Positive feedback regulation between IL10 and EGFR promotes lung cancer formation

    PubMed Central

    Hsu, Tsung-I; Wang, Yi-Chang; Hung, Chia-Yang; Yu, Chun-Hui; Su, Wu-Chou; Chang, Wen-Chang; Hung, Jan-Jong

    2016-01-01

    The role of IL10 in the tumorigenesis of various cancer types is still controversial. Here, we found that increased IL10 levels are correlated with a poor prognosis in lung cancer patients. Moreover, IL10 levels were significantly increased in the lungs and serum of EGFRL858R- and Kras4bG12D-induced lung cancer mice, indicating that IL10 might facilitate lung cancer tumorigenesis. IL10 knockout in EGFRL858R and Kras4bG12D mice inhibited the development of lung tumors and decreased the levels of infiltrating M2 macrophages and tumor-promoting Treg lymphocytes. We also showed that EGF increases IL10 expression by enhancing IL10 mRNA stability, and IL10 subsequently activates JAK1/STAT3, Src, PI3K/Akt, and Erk signaling pathways. Interestingly, the IL10-induced recruitment of phosphorylated Src was critical for inducing EGFR through the activation of the JAK1/STAT3 pathway, suggesting that Src and JAK1 positively regulate each other to enhance STAT3 activity. Doxycycline-induced EGFRL858R mice treated with gefitinib and anti-IL10 antibodies exhibited poor tumor formation. In conclusion, IL10 and EGFR regulate each other through positive feedback, which leads to lung cancer formation. PMID:26956044

  17. Positive feedback regulation between IL10 and EGFR promotes lung cancer formation.

    PubMed

    Hsu, Tsung-I; Wang, Yi-Chang; Hung, Chia-Yang; Yu, Chun-Hui; Su, Wu-Chou; Chang, Wen-Chang; Hung, Jan-Jong

    2016-04-12

    The role of IL10 in the tumorigenesis of various cancer types is still controversial. Here, we found that increased IL10 levels are correlated with a poor prognosis in lung cancer patients. Moreover, IL10 levels were significantly increased in the lungs and serum of EGFRL858R- and Kras4bG12D-induced lung cancer mice, indicating that IL10 might facilitate lung cancer tumorigenesis. IL10 knockout in EGFRL858R and Kras4bG12D mice inhibited the development of lung tumors and decreased the levels of infiltrating M2 macrophages and tumor-promoting Treg lymphocytes. We also showed that EGF increases IL10 expression by enhancing IL10 mRNA stability, and IL10 subsequently activates JAK1/STAT3, Src, PI3K/Akt, and Erk signaling pathways. Interestingly, the IL10-induced recruitment of phosphorylated Src was critical for inducing EGFR through the activation of the JAK1/STAT3 pathway, suggesting that Src and JAK1 positively regulate each other to enhance STAT3 activity. Doxycycline-induced EGFRL858R mice treated with gefitinib and anti-IL10 antibodies exhibited poor tumor formation. In conclusion, IL10 and EGFR regulate each other through positive feedback, which leads to lung cancer formation. PMID:26956044

  18. Implementation status of the global and local beam position feedback systems for the Advanced Photon Source storage ring

    SciTech Connect

    Chung, Y.; Barr, D.; Decker, G.; Galayda, J.; Kirchman, J.; Lenkszus, F.; Lumpkin, A.; Votaw, A.J.

    1995-07-01

    The Advanced Photon Source (APS) is implementing an extensive beam position feedback system for both global and local stabilization of particle and photon beams based on digital signal processing. The description and operational experience of the system will be given in this paper. In particular, we will discuss the underlying fundamental principles, hardware layout, controls interface, and automatic software generation for multiple digital signal processors (DSPS) distributed in 20 VME crates around the ring. The feedback system runs at 4-kHz sampling frequency in order to achieve the correction bandwidth of approximately 100 Hz. For the maximum correction efficiency and resolution of conflicts among multiple local feedback systems due to the local bump closure error, the global and local feedback systems are combined into a single unified system. This novel approach is made possible through data sharing among the global and local systems via the fiber-optically networked reflective memories.

  19. Coordination of the Arc Regulatory System and Pheromone-Mediated Positive Feedback in Controlling the Vibrio fischeri lux Operon

    PubMed Central

    Septer, Alecia N.; Stabb, Eric V.

    2012-01-01

    Bacterial pheromone signaling is often governed both by environmentally responsive regulators and by positive feedback. This regulatory combination has the potential to coordinate a group response among distinct subpopulations that perceive key environmental stimuli differently. We have explored the interplay between an environmentally responsive regulator and pheromone-mediated positive feedback in intercellular signaling by Vibrio fischeri ES114, a bioluminescent bacterium that colonizes the squid Euprymna scolopes. Bioluminescence in ES114 is controlled in part by N-(3-oxohexanoyl)-L-homoserine lactone (3OC6), a pheromone produced by LuxI that together with LuxR activates transcription of the luxICDABEG operon, initiating a positive feedback loop and inducing luminescence. The lux operon is also regulated by environmentally responsive regulators, including the redox-responsive ArcA/ArcB system, which directly represses lux in culture. Here we show that inactivating arcA leads to increased 3OC6 accumulation to initiate positive feedback. In the absence of positive feedback, arcA-mediated control of luminescence was only ∼2-fold, but luxI-dependent positive feedback contributed more than 100 fold to the net induction of luminescence in the arcA mutant. Consistent with this overriding importance of positive feedback, 3OC6 produced by the arcA mutant induced luminescence in nearby wild-type cells, overcoming their ArcA repression of lux. Similarly, we found that artificially inducing ArcA could effectively repress luminescence before, but not after, positive feedback was initiated. Finally, we show that 3OC6 produced by a subpopulation of symbiotic cells can induce luminescence in other cells co-colonizing the host. Our results suggest that even transient loss of ArcA-mediated regulation in a sub-population of cells can induce luminescence in a wider community. Moreover, they indicate that 3OC6 can communicate information about both cell density and the state of

  20. Load speed regulation in compliant mechanical transmission systems using feedback and feedforward control actions.

    PubMed

    Raul, P R; Dwivedula, R V; Pagilla, P R

    2016-07-01

    The problem of controlling the load speed of a mechanical transmission system consisting of a belt-pulley and gear-pair is considered. The system is modeled as two inertia (motor and load) connected by a compliant transmission. If the transmission is assumed to be rigid, then using either the motor or load speed feedback provides the same result. However, with transmission compliance, due to belts or long shafts, the stability characteristics and performance of the closed-loop system are quite different when either motor or load speed feedback is employed. We investigate motor and load speed feedback schemes by utilizing the singular perturbation method. We propose and discuss a control scheme that utilizes both motor and load speed feedback, and design an adaptive feedforward action to reject load torque disturbances. The control algorithms are implemented on an experimental platform that is typically used in roll-to-roll manufacturing and results are shown and discussed. PMID:27126600

  1. Local feedback mechanisms of the shallow water region around the Maritime Continent

    NASA Astrophysics Data System (ADS)

    Xue, Pengfei; Eltahir, Elfatih A. B.; Malanotte-Rizzoli, Paola; Wei, Jun

    2014-10-01

    The focus of this study is the local-scale air-sea feedback mechanisms over the shallow shelf water region (water depth <200 m) of the Maritime Continent (MC). MC was selected as a pilot study site for its extensive shallow water coverage, geographic complexity, and importance in the global climate system. To identify the local-scale air-sea feedback processes, we ran numerical experiments with perturbed surface layer water temperature using a coupled ocean-atmosphere model and an uncoupled ocean model. By examining the responses of the coupled and uncoupled models to the water temperature perturbation, we identify that, at a local-scale, a negative feedback process through the coupled dynamics that tends to restore the SST from its perturbation could dominate the shallow water region of the MC at a short time scale of several days. The energy budget shows that 38% of initial perturbation-induced heat energy was adjusted through the air-sea feedback mechanisms within 2 weeks, of which 58% is directly transferred into the atmosphere by the adjustment of latent heat flux due to the evaporative cooling mechanism. The increased inputs of heat and moisture into the lower atmosphere then modifies its thermal structure and increases the formation of low-level clouds, which act as a shield preventing incoming solar radiation from reaching the sea surface, accounts for 38% of the total adjustment of surface heat fluxes, serving as the second mechanism for the negative feedback process. The adjustment of sensible heat flux and net longwave radiation play a secondary role. The response of the coupled system to the SST perturbation suggests a response time scale of the coupled feedback process of about 3-5 days. The two-way air-sea feedback tightly links the surface heat fluxes, clouds and SST, and can play an important role in regulating the short-term variability of the SST over the shallow shelf water regions.

  2. Acetyl salicylic acid inhibits Th17 airway inflammation via blockade of IL-6 and IL-17 positive feedback.

    PubMed

    Moon, Hyung-Geun; Kang, Chil Sung; Choi, Jun-Pyo; Choi, Dong Sic; Choi, Hyun Il; Choi, Yong Wook; Jeon, Seong Gyu; Yoo, Joo-Yeon; Jang, Myoung Ho; Gho, Yong Song; Kim, Yoon-Keun

    2013-01-01

    T-helper (Th)17 cell responses are important for the development of neutrophilic inflammatory disease. Recently, we found that acetyl salicylic acid (ASA) inhibited Th17 airway inflammation in an asthma mouse model induced by sensitization with lipopolysaccharide (LPS)-containing allergens. To investigate the mechanism(s) of the inhibitory effect of ASA on the development of Th17 airway inflammation, a neutrophilic asthma mouse model was generated by intranasal sensitization with LPS plus ovalbumin (OVA) and then challenged with OVA alone. Immunologic parameters and airway inflammation were evaluated 6 and 48 h after the last OVA challenge. ASA inhibited the production of interleukin (IL)-17 from lung T cells as well as in vitro Th17 polarization induced by IL-6. Additionally, ASA, but not salicylic acid, suppressed Th17 airway inflammation, which was associated with decreased expression of acetyl-STAT3 (downstream signaling of IL-6) in the lung. Moreover, the production of IL-6 from inflammatory cells, induced by IL-17, was abolished by treatment with ASA, whereas that induced by LPS was not. Altogether, ASA, likely via its acetyl moiety, inhibits Th17 airway inflammation by blockade of IL-6 and IL-17 positive feedback. PMID:23306703

  3. An exploratory pilot study of mechanisms of action within normative feedback for adult drinkers

    PubMed Central

    Muench, Frederick J.; Lee, Rufina; Pena, Juan; Hail, Lisa

    2016-01-01

    Background. Normative feedback (NF), or receiving information about one’s drinking compared to peer drinking norms, is one of the most widely used brief interventions for prevention and intervention for hazardous alcohol use. NF has demonstrated predominantly small but significant effect sizes for intention to change and other drinking related outcomes. Identifying mechanisms of action may improve the effectiveness of NF; however, few studies have examined NF’s mechanisms of action, particularly among adults. Objective. This study is an exploratory analysis of two theorized mechanisms of NF: discrepancy (specifically personal dissonance—the affective response to feedback) and belief in the accuracy of feedback. Method. Using Amazon’s Mechanical Turk, 87 men (n = 56) and women (n = 31) completed an online survey during which they were asked about their perceptions about their drinking and actual drinking behaviors. Then participants were provided tailored NF and evaluated for their reactions. Severity of discrepancy was measured by the difference between one’s estimated percentile ranking of drinking compared to peers and actual percentile ranking. Surprise and worry reported due to the discrepancy were proxies for personal dissonance. Participants were also asked if they believed the feedback and if they had any plans to change their drinking. Mediation analyses were implemented, exploring whether surprise, worry, or belief in the accuracy of feedback mediated severity of discrepancy’s impact on plan for change. Results. Among this sample of adult drinkers, severity of discrepancy did not predict plan for change, and personal dissonance did not mediate severity of discrepancy. Severity of discrepancy was mediated by belief in the accuracy of feedback. In addition, viewing one’s drinking as a problem prior to feedback and post-NF worry both predicted plan for change independently. Conclusions. Results revealed that NF may not work to create personal

  4. An epidemic spreading model on adaptive scale-free networks with feedback mechanism

    NASA Astrophysics Data System (ADS)

    Li, Tao; Liu, Xiongding; Wu, Jie; Wan, Chen; Guan, Zhi-Hong; Wang, Yuanmei

    2016-05-01

    A SIRS epidemic model with feedback mechanism on adaptive scale-free networks is presented. Using the mean field theory the spreading dynamics of the epidemic is studied in detail. The basic reproductive number and equilibriums are derived. Theoretical results indicate that the basic reproductive number is significantly dependent on the topology of the underlying networks. The existence of equilibriums is determined by the basic reproductive number. The global stability of disease-free equilibrium and the epidemic permanence are proved in detail. The feedback mechanism cannot change the basic reproductive number, but it can reduce the endemic level and weaken the epidemic spreading. Numerical simulations confirmed the analytical results.

  5. Importance of positive feedbacks and overconfidence in a self-fulfilling Ising model of financial markets

    NASA Astrophysics Data System (ADS)

    Sornette, Didier; Zhou, Wei-Xing

    2006-10-01

    Following a long tradition of physicists who have noticed that the Ising model provides a general background to build realistic models of social interactions, we study a model of financial price dynamics resulting from the collective aggregate decisions of agents. This model incorporates imitation, the impact of external news and private information. It has the structure of a dynamical Ising model in which agents have two opinions (buy or sell) with coupling coefficients, which evolve in time with a memory of how past news have explained realized market returns. We study two versions of the model, which differ on how the agents interpret the predictive power of news. We show that the stylized facts of financial markets are reproduced only when agents are overconfident and mis-attribute the success of news to predict return to herding effects, thereby providing positive feedbacks leading to the model functioning close to the critical point. Our model exhibits a rich multifractal structure characterized by a continuous spectrum of exponents of the power law relaxation of endogenous bursts of volatility, in good agreement with previous analytical predictions obtained with the multifractal random walk model and with empirical facts.

  6. A computerized tablet with visual feedback of hand position for functional magnetic resonance imaging

    PubMed Central

    Karimpoor, Mahta; Tam, Fred; Strother, Stephen C.; Fischer, Corinne E.; Schweizer, Tom A.; Graham, Simon J.

    2015-01-01

    Neuropsychological tests behavioral tasks that very commonly involve handwriting and drawing are widely used in the clinic to detect abnormal brain function. Functional magnetic resonance imaging (fMRI) may be useful in increasing the specificity of such tests. However, performing complex pen-and-paper tests during fMRI involves engineering challenges. Previously, we developed an fMRI-compatible, computerized tablet system to address this issue. However, the tablet did not include visual feedback of hand position (VFHP), a human factors component that may be important for fMRI of certain patient populations. A real-time system was thus developed to provide VFHP and integrated with the tablet in an augmented reality display. The effectiveness of the system was initially tested in young healthy adults who performed various handwriting tasks in front of a computer display with and without VFHP. Pilot fMRI of writing tasks were performed by two representative individuals with and without VFHP. Quantitative analysis of the behavioral results indicated improved writing performance with VFHP. The pilot fMRI results suggest that writing with VFHP requires less neural resources compared to the without VFHP condition, to maintain similar behavior. Thus, the tablet system with VFHP is recommended for future fMRI studies involving patients with impaired brain function and where ecologically valid behavior is important. PMID:25859201

  7. Speciation as a positive feedback loop between postzygotic and prezygotic barriers to gene flow.

    PubMed Central

    Servedio, Maria R; Saetre, Glenn-Peter

    2003-01-01

    Speciation is intimately associated with the evolution of sex-and-reproduction-related traits, including those affecting hybrid incompatibility (postzygotic isolation) and species recognition (prezygotic isolation). Genes controlling such traits are not randomly distributed in the genome but are particularly abundant on the sex chromosomes. However, the evolutionary consequences of the sex linkage of genes involved in speciation have been little explored. Here, we present simulations of a continent-island diploid model that examines the effects of reduced recombination using both autosomal and sex-linked inheritance. We show first that linkage between genes affecting postzygotic and prezygotic isolation leads to a positive feedback loop in which both are strengthened. As species recognition evolves, genes causing hybrid incompatibility will hitchhike along with those improving premating isolation, leading to stronger hybrid incompatibility and thus increased pressure for further preference divergence. Second, we show that this loop effect is generally enhanced by sex linkage, because recombination is eliminated in the heterogametic sex, leading to tighter effective linkage between the two classes of genes and because natural selection is more efficient at sex-linked loci, as recessive alleles are not masked by dominance in the heterogametic sex. Accordingly, hitchhiking can be important in promoting speciation and can also lead to increased postzygotic isolation through adaptive evolution. PMID:12965012

  8. Positive feedback regulation of p53 transactivity by DNA damage-induced ISG15 modification

    PubMed Central

    Park, Jong Ho; Yang, Seung Wook; Park, Jung Mi; Ka, Seung Hyeun; Kim, Ji-Hoon; Kong, Young-Yun; Jeon, Young Joo; Seol, Jae Hong; Chung, Chin Ha

    2016-01-01

    p53 plays a pivotal role in tumour suppression under stresses, such as DNA damage. ISG15 has been implicated in the control of tumorigenesis. Intriguingly, the expression of ISG15, UBE1L and UBCH8 is induced by DNA-damaging agents, such as ultraviolet and doxorubicin, which are known to induce p53. Here, we show that the genes encoding ISG15, UBE1L, UBCH8 and EFP, have the p53-responsive elements and their expression is induced in a p53-dependent fashion under DNA damage conditions. Furthermore, DNA damage induces ISG15 conjugation to p53 and this modification markedly enhances the binding of p53 to the promoters of its target genes (for example, CDKN1 and BAX) as well as of its own gene by promoting phosphorylation and acetylation, leading to suppression of cell growth and tumorigenesis. These findings establish a novel feedback circuit between p53 and ISG15-conjugating system for positive regulation of the tumour suppressive function of p53 under DNA damage conditions. PMID:27545325

  9. Benefit of educational feedback for the use of positive expiratory pressure device

    PubMed Central

    Reychler, Gregory; Jacquemart, Manon; Poncin, William; Aubriot, Anne-Sophie; Liistro, Giuseppe

    2015-01-01

    BACKGROUND: Positive expiratory pressure (PEP) is regularly used as a self-administered airway clearance technique. OBJECTIVE: The aim of this study was to evaluate the need to teach the correct use of the PEP device and to measure the progress of the success rate of the maneuver after training. METHOD: A PEP system (PariPEP-S Sytem) was used to generate PEP in 30 healthy volunteers. They were instructed by a qualified physical therapist to breathe correctly through the PEP device. Then they were evaluated during a set of ten expirations. Two other evaluations were performed at day 2 and day 8 (before and after feedback). The mean PEP and the success rate were calculated for each set of expirations. The number of maneuvers needed to obtain a correct use was calculated on the first session. RESULTS: An optimal PEP was reached after 7.5 SD 2.7 attempts by all subjects. Success rates and mean pressures were similar between the different sets of expirations (p=0.720 and p=0.326, respectively). Pressure variability was around 10%. After one week, 30% of subjects generated more than two non-optimal pressures in the set of ten expirations. No difference in success rate was observed depending on the evaluations. CONCLUSION: This study demonstrates that good initial training on the use of the PEP device and regular follow-up are required for the subject to reach optimal expiratory pressure. PMID:26647746

  10. Far-Infrared Surface Emissivity Impacts on Climate and the Potential for a Positive Feedback

    NASA Astrophysics Data System (ADS)

    Feldman, D.; Collins, W.; Huang, X.; Chen, X.; Walden, V. P.

    2014-12-01

    There are few observational constraints on surface emissivity at wavelengths longer than 15 μm, a spectral region commonly referred to as the far-infrared. Nevertheless, where the precipitable water vapor (PWV) is less than 1 mm, which is common at high latitudes and high altitudes, the infrared energy budget is directly impacted by this emissivity. Calculations based on published indices of refraction of ice, water, and common surficial minerals, and observations based on a limited set of spectroscopic measurements, find that non-frozen ocean and desert scenes will exhibit lower far-infrared surface emissivity than frozen scenes by between 0.1 and 0.2. The representation of surface emissivity in climate models is highly simplified, based on ideal black-body emission, and systematically higher than emissivity of real surfaces. Therefore, we performed sensitivity studies using the Community Earth System Model (CESM) and found that Arctic surface temperatures warm by 2 °K and frozen surface extent decreases by 5-10% when the model is subjected to realistic values of far-infrared surface emissivity. This finding may help explain the cold-pole bias, and also suggests the potential for a positive feedback whereby the loss of snow or ice leads to the exposure of surfaces that reduce surface infrared cooling, thus warming the surface further.

  11. Dominant pole and eigenstructure assignment for positive systems with state feedback

    NASA Astrophysics Data System (ADS)

    Li, Zhao; Lam, James

    2016-09-01

    In this paper, the dominant pole assignment problem, the dominant eigenstructure assignment problem and the robust dominant pole assignment problem for linear time-invariant positive systems with state feedback are considered. The dominant pole assignment problem is formulated as a linear programming problem, and the dominant eigenstructure problem is formulated as a quasiconvex optimisation problem with linear constraints. The robust dominant pole assignment problem is formulated as a non-convex optimisation problem with non-linear constraints which is solved using particle swarm optimisation (PSO) with an efficient scheme which employs the dominant eigenstructure assignment technique to accelerate the convergence of the PSO procedure. Each of the three problems can be further constrained by requiring that the controller has a pre-specified structure, or the gain matrix have both elementwise upper and lower bounds. These constraints can be incorporated into the proposed scheme without increasing the complexity of the algorithms. Both the continuous-time case and the discrete-time case are treated in the paper.

  12. Comparing position and force control for interactive molecular simulators with haptic feedback.

    PubMed

    Bolopion, Aude; Cagneau, Barthélemy; Redon, Stephane; Régnier, Stéphane

    2010-09-01

    This paper presents a novel tool for the analysis of new molecular structures which enables a wide variety of manipulations. It is composed of a molecular simulator and a haptic device. The simulation software deals with systems of hundreds or thousands of degrees of freedom and computes the reconfiguration of the molecules in a few tenths of a second. For the ease of manipulation and to help the operator understand nanoscale phenomena, a haptic device is connected to the simulator. To handle a wide variety of applications, both position and force control are implemented. To our knowledge, this is the first time the applications of force control are detailed for molecular simulation. These two control modes are compared in terms of adequacy with molecular dynamics, transparency and stability sensitivity with respect to environmental conditions. Based on their specificity the operations they can realize are detailed. Experiments highlight the usability of our tool for the different steps of the analysis of molecular structures. It includes the global reconfiguration of a molecular system, the measurement of molecular properties and the comprehension of nanoscale interactions. Compared to most existing systems, the one developed in this paper offers a wide range of possible experiments. The detailed analysis of the properties of the control modes can be easily used to implement haptic feedback on other molecular simulators. PMID:20727801

  13. Positive, But Not Negative Feedback Actions of Estradiol in Adult Female Mice Require Estrogen Receptor α in Kisspeptin Neurons

    PubMed Central

    Dubois, Sharon L.; Acosta-Martínez, Maricedes; DeJoseph, Mary R.; Wolfe, Andrew; Radovick, Sally; Boehm, Ulrich; Urban, Janice H.

    2015-01-01

    Hypothalamic kisspeptin (Kiss1) neurons express estrogen receptor α (ERα) and exert control over GnRH/LH secretion in female rodents. It has been proposed that estradiol (E2) activation of ERα in kisspeptin neurons in the arcuate nucleus (ARC) suppresses GnRH/LH secretion (negative feedback), whereas E2 activation of ERα in kisspeptin neurons in the anteroventral periventricular nucleus (AVPV) mediates the release of preovulatory GnRH/LH surges (positive feedback). To test these hypotheses, we generated mice bearing kisspeptin cell–specific deletion of ERα (KERαKO) and treated them with E2 regimens that evoke either negative or positive feedback actions on GnRH/LH secretion. Using negative feedback regimens, as expected, E2 effectively suppressed LH levels in ovariectomized (OVX) wild-type (WT) mice to the levels seen in ovary-intact mice. Surprisingly, however, despite the fact that E2 regulation of Kiss1 mRNA expression was abrogated in both the ARC and AVPV of KERαKO mice, E2 also effectively decreased LH levels in OVX KERαKO mice to the levels seen in ovary-intact mice. Conversely, using a positive feedback regimen, E2 stimulated LH surges in WT mice, but had no effect in KERαKO mice. These experiments clearly demonstrate that ERα in kisspeptin neurons is required for the positive, but not negative feedback actions of E2 on GnRH/LH secretion in adult female mice. It remains to be determined whether the failure of KERαKO mice to exhibit GnRH/LH surges reflects the role of ERα in the development of kisspeptin neurons, in the active signaling processes leading to the release of GnRH/LH surges, or both. PMID:25545386

  14. A phase plane graph based model of the ovulatory cycle lacking the "positive feedback" phenomenon

    PubMed Central

    2012-01-01

    When hormones during the ovulatory cycle are shown in phase plane graphs, reported FSH and estrogen values form a specific pattern that resembles the leaning “&" symbol, while LH and progesterone (Pg) values form a "boomerang" shape. Graphs in this paper were made using data reported by Stricker et al. [Clin Chem Lab Med 2006;44:883–887]. These patterns were used to construct a simplistic model of the ovulatory cycle without the conventional "positive feedback" phenomenon. The model is based on few well-established relations: hypothalamic GnRH secretion is increased under estrogen exposure during two weeks that start before the ovulatory surge and lasts till lutheolysis. the pituitary GnRH receptors are so prone to downregulation through ligand binding that this must be important for their function. in several estrogen target tissue progesterone receptor (PgR) expression depends on previous estrogen binding to functional estrogen receptors (ER), while Pg binding to the expressed PgRs reduces both ER and PgR expression. Some key features of the presented model are here listed: High GnRH secretion induced by the recovered estrogen exposure starts in the late follicular phase and lasts till lutheolysis. The LH and FSH surges start due to combination of accumulated pituitary GnRH receptors and increased GnRH secretion. The surges quickly end due to partial downregulation of the pituitary GnRH receptors (64% reduction of the follicular phase pituitary GnRH receptors is needed to explain the reported LH drop after the surge). A strong increase in the lutheal Pg blood level, despite modest decline in LH levels, is explained as delayed expression of pituitary PgRs. Postponed pituitary PgRs expression enforces a negative feedback loop between Pg levels and LH secretions not before the mid lutheal phase. Lutheolysis is explained as a consequence of Pg binding to hypothalamic and pituitary PgRs that reduces local ER expression. When hypothalamic sensitivity to estrogen is

  15. Video-Feedback Intervention to Promote Positive Parenting Adapted to Autism (VIPP-AUTI): A Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Poslawsky, Irina E; Naber, Fabiënne BA; Bakermans-Kranenburg, Marian J; van Daalen, Emma; van Engeland, Herman; van IJzendoorn, Marinus H

    2015-01-01

    In a randomized controlled trial, we evaluated the early intervention program Video-feedback Intervention to promote Positive Parenting adapted to Autism (VIPP-AUTI) with 78 primary caregivers and their child (16-61 months) with Autism Spectrum Disorder. VIPP-AUTI is a brief attachment-based intervention program, focusing on improving parent-child…

  16. Does Gender Influence Emotions Resulting from Positive Applause Feedback in Self-Assessment Testing? Evidence from Neuroscience

    ERIC Educational Resources Information Center

    Liu, Chia-Ju; Huang, Chin-Fei; Liu, Ming-Chi; Chien, Yu-Cheng; Lai, Chia-Hung; Huang, Yueh-Min

    2015-01-01

    Computerized self-assessment testing can help learners reflect on learning content and can also promote their motivation toward learning. However, a positive affective state is the key to achieving these learning goals. This study aims to examine learning gains and emotional reactions resulting from receiving emotional feedback in the form of…

  17. Method to quantify accuracy of position feedback signals of a three-dimensional two-photon laser-scanning microscope

    PubMed Central

    Kummer, Michael; Kirmse, Knut; Witte, Otto W.; Haueisen, Jens; Holthoff, Knut

    2015-01-01

    Two-photon laser-scanning microscopy enables to record neuronal network activity in three-dimensional space while maintaining single-cellular resolution. One of the proposed approaches combines galvanometric x-y scanning with piezo-driven objective movements and employs hardware feedback signals for position monitoring. However, readily applicable methods to quantify the accuracy of those feedback signals are currently lacking. Here we provide techniques based on contact-free laser reflection and laser triangulation for the quantification of positioning accuracy of each spatial axis. We found that the lateral feedback signals are sufficiently accurate (defined as <2.5 µm) for a wide range of scan trajectories and frequencies. We further show that axial positioning accuracy does not only depend on objective acceleration and mass but also its geometry. We conclude that the introduced methods allow a reliable quantification of position feedback signals in a cost-efficient, easy-to-install manner and should be applicable for a wide range of two-photon laser scanning microscopes. PMID:26504620

  18. Method to quantify accuracy of position feedback signals of a three-dimensional two-photon laser-scanning microscope.

    PubMed

    Kummer, Michael; Kirmse, Knut; Witte, Otto W; Haueisen, Jens; Holthoff, Knut

    2015-10-01

    Two-photon laser-scanning microscopy enables to record neuronal network activity in three-dimensional space while maintaining single-cellular resolution. One of the proposed approaches combines galvanometric x-y scanning with piezo-driven objective movements and employs hardware feedback signals for position monitoring. However, readily applicable methods to quantify the accuracy of those feedback signals are currently lacking. Here we provide techniques based on contact-free laser reflection and laser triangulation for the quantification of positioning accuracy of each spatial axis. We found that the lateral feedback signals are sufficiently accurate (defined as <2.5 µm) for a wide range of scan trajectories and frequencies. We further show that axial positioning accuracy does not only depend on objective acceleration and mass but also its geometry. We conclude that the introduced methods allow a reliable quantification of position feedback signals in a cost-efficient, easy-to-install manner and should be applicable for a wide range of two-photon laser scanning microscopes. PMID:26504620

  19. Visual Feedback of the Non-Moving Limb Improves Active Joint-Position Sense of the Impaired Limb in Spastic Hemiparetic Cerebral Palsy

    ERIC Educational Resources Information Center

    Smorenburg, Ana R. P.; Ledebt, Annick; Deconinck, Frederik J. A.; Savelsbergh, Geert J. P.

    2011-01-01

    This study examined the active joint-position sense in children with Spastic Hemiparetic Cerebral Palsy (SHCP) and the effect of static visual feedback and static mirror visual feedback, of the non-moving limb, on the joint-position sense. Participants were asked to match the position of one upper limb with that of the contralateral limb. The task…

  20. Mammary blood flow and metabolic activity are linked by a feedback mechanism involving nitric oxide synthesis.

    PubMed

    Cieslar, S R L; Madsen, T G; Purdie, N G; Trout, D R; Osborne, V R; Cant, J P

    2014-01-01

    To test which, if any, of the major milk precursors can elicit a rapid change in the rate of mammary blood flow (MBF) and to define the time course and magnitude of such changes, 4 lactating cows were infused with glucose, amino acids, or triacylglycerol into the external iliac artery feeding one udder half while iliac plasma flow (IPF) was monitored continuously by dye dilution. Adenosine and saline were infused as positive and negative controls, respectively, and insulin was infused to characterize the response to a centrally produced anabolic hormone. To test the roles of cyclooxygenase, NO synthase and ATP-sensitive K (KATP) channels in nutrient-mediated changes in blood flow, their respective inhibitors-indomethacin, Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME), and glibenclamide-were infused simultaneously with glucose. Each day, 1 infusate was given twice to each cow, over a 20-min period each time, separated by a 20-min washout period. In addition, each treatment protocol was administered on 2 separate days. A 73% increase in IPF during adenosine infusion showed that the mammary vasodilatory response was quadratic in time, with most changes occurring in the first 5min. Glucose infusion decreased IPF by 9% in a quadratic manner, most rapidly in the first 5min, indicating that a feedback mechanism of local blood flow control, likely through adenosine release, was operative in the mammary vasculature. Amino acid infusion increased IPF 9% in a linear manner, suggesting that mammary ATP utilization was stimulated more than ATP production. This could reflect a stimulation of protein synthesis. Triacylglycerol only tended to decrease IPF and insulin did not affect IPF. A lack of IPF response to glibenclamide indicates that KATP channels are not involved in MBF regulation. Indomethacin and L-NAME both depressed IPF. In the presence of indomethacin, glucose infusion caused a quadratic 9% increase in IPF. Indomethacin is an inhibitor of mitochondrial

  1. Distinct noise-controlling roles of multiple negative feedback mechanisms in a prokaryotic operon system.

    PubMed

    Nguyen, L K; Kulasiri, D

    2011-03-01

    Molecular fluctuations are known to affect dynamics of cellular systems in important ways. Studies aimed at understanding how molecular systems of certain regulatory architectures control noise therefore become essential. The interplay between feedback regulation and noise has been previously explored for cellular networks governed by a single negative feedback loop. However, similar issues within networks consisting of more complex regulatory structures remain elusive. The authors investigate how negative feedback loops manage noise within a biochemical cascade concurrently governed by multiple negative feedback loops, using the prokaryotic tryptophan (trp) operon system in Escherechia coli as the model system. To the authors knowledge, this is the first study of noise in the trp operon system. They show that the loops in the trp operon system possess distinct, even opposing, noise-controlling effects despite their seemingly analogous feedback structures. The enzyme inhibition loop, although controlling the last reaction of the cascade, was found to suppress noise not only for the tryptophan output but also for other upstream components. In contrast, the Repression (Rep) loop enhances noise for all systems components. Attenuation (Att) poses intermediate effects by attenuating noise for the upstream components but promoting noise for components downstream of its target. Regarding noise at the output tryptophan, Rep and Att can be categorised as noise-enhancing loops whereas Enzyme Inhibition as a noise-reducing loop. These findings suggest novel implications in how cellular systems with multiple feedback mechanisms control noise. [Includes supplementary material]. PMID:21405203

  2. TLR4 signaling promotes a COX-2/PGE2/STAT3 positive feedback loop in hepatocellular carcinoma (HCC) cells

    PubMed Central

    Lin, Ang; Wang, Guan; Zhao, Huajun; Zhang, Yuyi; Han, Qiuju; Zhang, Cai; Tian, Zhigang; Zhang, Jian

    2016-01-01

    ABSTRACT Toll-like receptors (TLRs) can be expressed by tumor cells, and each TLR exhibits different biological functions. Evidences showed the activation of some certain TLRs could promote tumor progression. One of which TLR4 has been found to promote hepatocellular carcinoma (HCC) cells proliferation, but the detailed mechanism is still unknown. In the present study, we verified that TLR4 was functionally expressed on HCC cells, and TLR4 agonist lipopolysaccharide (LPS) could stimulate the proliferation and clone formation of HCC cells. Most importantly, we found a COX-2/PGE2/STAT3 positive feedback loop exists in HCC cells, which could be provoked by TLR4 activation. Consistently, the expression of TLR4, COX-2 and p-STAT3Y705 was positively correlated with each other in liver tumor tissues from patients with primary HCC. Further investigation demonstrated this loop played a dominant role in TLR4-induced HCC cell proliferation and multidrug resistance (MDR) to chemotherapy. Inhibition of TLR4 or COX-2/PGE2/STAT3 loop would attenuate LPS-induced inflammation and proliferation of HCC cells, and enhance the sensitivity of HCC cells to chemotherapeutics in vitro. By using a primary HCC model, we observed COX-2/PGE2/STAT3 loop was significantly blocked in TLR4−/− mice compared to wild type mice, and there was no obvious tumorgenesis sign in TLR4−/− mice. Therefore, these findings provided the precise molecular mechanism of TLR4 signaling pathway involved in HCC progress, and suggested that TLR4 may be a promising target for HCC treatment. PMID:27057441

  3. Version pressure feedback mechanisms for speculative versioning caches

    DOEpatents

    Eichenberger, Alexandre E.; Gara, Alan; O& #x27; Brien, Kathryn M.; Ohmacht, Martin; Zhuang, Xiaotong

    2013-03-12

    Mechanisms are provided for controlling version pressure on a speculative versioning cache. Raw version pressure data is collected based on one or more threads accessing cache lines of the speculative versioning cache. One or more statistical measures of version pressure are generated based on the collected raw version pressure data. A determination is made as to whether one or more modifications to an operation of a data processing system are to be performed based on the one or more statistical measures of version pressure, the one or more modifications affecting version pressure exerted on the speculative versioning cache. An operation of the data processing system is modified based on the one or more determined modifications, in response to a determination that one or more modifications to the operation of the data processing system are to be performed, to affect the version pressure exerted on the speculative versioning cache.

  4. A study on positive-feedback configuration of a bipolar SiC high temperature operational amplifier

    NASA Astrophysics Data System (ADS)

    Kargarrazi, Saleh; Lanni, Luigia; Zetterling, Carl-Mikael

    2016-02-01

    This paper reports on the design and implementation of an integrated operational amplifier in bipolar SiC, and elaborates on its operation in positive-feedback configuration.The opamp is studied in different feedback setups: closed-loop compensated amplifier, comparator with hysteresis (Schmitt trigger), and as a relaxation oscillator. Measurement results suggest a stable closed-loop opamp with ∼40 dB gain, a Schmitt trigger with constant threshold levels over a wide temperature range, and a relaxation oscillator tested up to 540 kHz. All the setups were tested from 25 °C up to 500 °C.

  5. Filtering for distributed mechanical systems using position measurements: perspectives in medical imaging

    NASA Astrophysics Data System (ADS)

    Moireau, Philippe; Chapelle, Dominique; LeTallec, Patrick

    2009-03-01

    We propose an effective filtering methodology designed to perform estimation in a distributed mechanical system using position measurements. As in a previously introduced method, the filter is inspired by robust control feedback, but here we take full advantage of the estimation specificity to choose a feedback law that can act on displacements instead of velocities and still retain the same kind of dissipativity property which guarantees robustness. This is very valuable in many applications for which positions are more readily available than velocities, as in medical imaging. We provide an in-depth analysis of the proposed procedure, as well as detailed numerical assessments using a test problem inspired by cardiac biomechanics, as medical diagnosis assistance is an important perspective for this approach. The method is formulated first for measurements based on Lagrangian displacements, but we then derive a nonlinear extension allowing us to instead consider segmented images, which of course is even more relevant in medical applications.

  6. Star formation driven mechanical feedback in molecular clouds

    NASA Astrophysics Data System (ADS)

    Cunningham, Andrew J.

    The ubiquity and high density of outflows from young stars in clusters make them an intriguing candidate for the source of turbulence energy in molecular clouds. This work addresses, by direct numerical simulation, elements of protostellar outflow evolution that is relevant to their ability to drive turbulent flows in molecular clouds. The result of this work is surprising in that it shows that fossil cavities, rather than how shocks from active outflows, constitute the primary avenue by which outflows re-energize turbulence. This work first considers collisions between active jets, showing that this process is ineffective at converting the directed momentum and mechanical energy of outflows into turbulence. This effect is due to radiative energy loss which constrains the surface area through which colliding outflows entrain ambient gas. Recent observational results are discussed which indicate that fossil cavities from extinct outflows are abundant in molecular material surrounding clusters such as NGC1333. These structures, rather than the bow shocks of active outflows, comprise the link between outflow energy input, and re-energizing turbulence in the parent molecular cloud core. Numerical simulations are presented winch confirm that the evolution of cavities front decaying outflow sources leads to structures which match the observations of fossil cavities. The algorithms and tests of the AstroBEAR adaptive mesh refinement code for astrophysical magnetohydrodynamics are also presented. The code was developed during the course of this work and used for the numerical simulations.

  7. 78 FR 36190 - Agency Information Collection Activities; Submission for OMB Review; IT Dashboard Feedback Mechanism

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-17

    ... request to review and approve a previously approved information collection requirement regarding IT Dashboard Feedback Mechanism. A notice was published in the Federal Register at 78 FR 13057, on February 26... ADMINISTRATION Agency Information Collection Activities; Submission for OMB Review; IT Dashboard...

  8. Landscape Urbanization and Economic Growth in China: Positive Feedbacks and Sustainability Dilemmas

    PubMed Central

    2011-01-01

    Accelerating urbanization has been viewed as an important instrument for economic development and reducing regional income disparity in some developing countries, including China. Recent studies (Bloom et al. 2008) indicate that demographic urbanization level has no causal effect on economic growth. However, due to the varying and changing definition of urban population, the use of demographic indicators as a sole representing indicator for urbanization might be misleading. Here, we re-examine the causal relationship between urbanization and economic growth in Chinese cities and provinces in recent decades, using built-up areas as a landscape urbanization indicator. Our analysis shows that (1) larger cities, both in terms of population size and built-up area, and richer cities tend to gain more income, have larger built-up area expansion, and attract more population, than poorer cities or smaller cities; and (2) that there is a long-term bidirectional causality between urban built-up area expansion and GDP per capita at both city and provincial level, and a short-term bidirectional causality at provincial level, revealing a positive feedback between landscape urbanization and urban and regional economic growth in China. Our results suggest that urbanization, if measured by a landscape indicator, does have causal effect on economic growth in China, both within the city and with spillover effect to the region, and that urban land expansion is not only the consequences of economic growth in cities, but also drivers of such growth. The results also suggest that under its current economic growth model, it might be difficult for China to control urban expansion without sacrificing economic growth, and China’s policy to stop the loss of agricultural land, for food security, might be challenged by its policy to promote economic growth through urbanization. PMID:22103244

  9. Landscape urbanization and economic growth in China: positive feedbacks and sustainability dilemmas.

    PubMed

    Bai, Xuemei; Chen, Jing; Shi, Peijun

    2012-01-01

    Accelerating urbanization has been viewed as an important instrument for economic development and reducing regional income disparity in some developing countries, including China. Recent studies (Bloom et al. 2008) indicate that demographic urbanization level has no causal effect on economic growth. However, due to the varying and changing definition of urban population, the use of demographic indicators as a sole representing indicator for urbanization might be misleading. Here, we re-examine the causal relationship between urbanization and economic growth in Chinese cities and provinces in recent decades, using built-up areas as a landscape urbanization indicator. Our analysis shows that (1) larger cities, both in terms of population size and built-up area, and richer cities tend to gain more income, have larger built-up area expansion, and attract more population, than poorer cities or smaller cities; and (2) that there is a long-term bidirectional causality between urban built-up area expansion and GDP per capita at both city and provincial level, and a short-term bidirectional causality at provincial level, revealing a positive feedback between landscape urbanization and urban and regional economic growth in China. Our results suggest that urbanization, if measured by a landscape indicator, does have causal effect on economic growth in China, both within the city and with spillover effect to the region, and that urban land expansion is not only the consequences of economic growth in cities, but also drivers of such growth. The results also suggest that under its current economic growth model, it might be difficult for China to control urban expansion without sacrificing economic growth, and China's policy to stop the loss of agricultural land, for food security, might be challenged by its policy to promote economic growth through urbanization. PMID:22103244

  10. ADAMTS-7 forms a positive feedback loop with TNF-α in the pathogenesis of osteoarthritis

    PubMed Central

    Lai, Yongjie; Bai, Xiaohui; Zhao, Yunpeng; Tian, Qingyun; Liu, Ben; Lin, Edward A.; Chen, Yuqing; Lee, Brendan; Appleton, C Thomas G.; Beier, Frank; Yu, Xiu-Ping; Liu, Chuan-ju

    2015-01-01

    Objective To examine the expression of ADAMTS-7 during the progression of osteoarthritis (OA), defining its role in the pathogenesis of OA, and elucidating the molecular events involved. Methods ADAMTS-7 expression in cartilage of a rat OA model was assayed using immunohistochemistry. Cartilage-specific ADAMTS-7 transgenic mice and ADAMTS-7 small interfering (si)RNA knockdown mice were generated and used to analyse OA progression in both spontaneous and surgically induced OA models. Cartilage degradation and OA was evaluated using Safranin-O staining, immunohistochemistry, ELISA and western blotting. In addition, mRNA expression of tumour necrosis factor (TNF)-α and metalloproteinases known to be involved in cartilage degeneration in OA was analysed. Furthermore, the transactivation of ADAMTS-7 by TNF-α and its downstream NF-κB signalling was measured using reporter gene assay. Results ADAMTS-7 expression was elevated during disease progression in the surgically induced rat OA model. Targeted overexpression of ADAMTS-7 in chondrocytes led to chondrodysplasia characterised by short-limbed dwarfism and a delay in endochondral ossification in ‘young mice’ and a spontaneous OA-like phenotype in ‘aged’ mice. In addition, overexpression of ADAMTS-7 led to exaggerated breakdown of cartilage and accelerated OA progression, while knockdown of ADAMTS-7 attenuated degradation of cartilage matrix and protected against OA development, in surgically induced OA models. ADAMTS-7 upregulated TNF-α and metalloproteinases associated with OA; in addition, TNF-α induced ADAMTS-7 through NF-κB signalling. Conclusions ADAMTS-7 and TNF-α form a positive feedback loop in the regulation of cartilage degradation and OA progression, making them potential molecular targets for prevention and treatment of joint degenerative diseases, including OA. PMID:23928557

  11. Feedback inhibition of ENaC: Acute and chronic mechanisms

    PubMed Central

    Patel, Ankit B; Yang, Lei; Deng, Su; Palmer, Lawrence G

    2014-01-01

    Intracellular [Na+] ([Na+]i) modulates the activity of the epithelial Na channel (ENaC) to help prevent cell swelling and regulate epithelial Na+ transport, but the underlying mechanisms remain unclear. We show here that short-term (60–80 min) incubation of ENaC-expressing oocytes in high Na+ results in a 75% decrease in channel activity. When the β subunit was truncated, corresponding to a gain-of-function mutation found in Liddle's syndrome, the same maneuver reduced activity by 45% despite a larger increase in [Na+]i. In both cases the inhibition occurred with little to no change in cell-surface expression of γENaC. Long-term incubation (18 hours) in high Na+ reduced activity by 92% and 75% in wild-type channels and Liddle's mutant, respectively, with concomitant 70% and 52% decreases in cell-surface γENaC. In the presence of Brefeldin A to inhibit forward protein trafficking, high-Na+ incubation decreased wt ENaC activity by 52% and 88% after 4 and 8 hour incubations, respectively. Cleaved γENaC at the cell surface had lifetimes at the surface of 6 hrs in low Na+ and 4 hrs in high Na+, suggesting that [Na+]i increased the rate of retrieval of cleaved γ ENaC by 50%. This implies that enhanced retrieval of ENaC channels at the cell surface accounts for part, but not all, of the downregulation of ENaC activity shown with chronic increases in [Na+]i. PMID:25483587

  12. A general non-equilibrium framework for the parameterization of positive and negative feedbacks in atmospheric systems

    NASA Astrophysics Data System (ADS)

    Garrett, T. J.

    2012-12-01

    For any identifiable system, regardless of its complexity or scale, evolution can be treated as a spontaneous thermodynamic response to a local convergence of down-gradient material flows. In climate studies, examples of identifiable systems might include cloud cover or the global incidence of temperatures warmer than a certain threshold. Here it is shown how the time-dependent evolution of such systems is constrained by positive and negative feedbacks that fall into a few mathematically distinct modes. In general, evolution depends on the time integral of past flows and the current availability of material and energetic resources. More specifically, negative feedbacks arise from the depletion or predation of the material and potential energy reservoirs that supply the system. Positive feedbacks are due to either new reservoir "discovery" or system expansion into existing reservoirs. When positive feedbacks dominate, the time dependent response of system growth falls into a few clearly identifiable behaviors that include a law of diminishing returns, logistic behavior, and, if reservoirs are expanding very rapidly, unstable super-exponential or explosive growth. For open systems (e.g. radiative flows in our atmosphere) that have a resolved sink as well as a source, oscillatory behavior emerges and can be characterized in terms of a slightly modified form of the predator-prey equations commonly employed in ecology. The perturbation formulation of these equations is equivalent to a damped simple harmonic oscillator. Specific examples of non-equilibrium positive and negative feedback response can be described for the sudden development of rain and the oscillatory evolution of open-celled stratocumulus cloud decks.

  13. CaCDPK15 positively regulates pepper responses to Ralstonia solanacearum inoculation and forms a positive-feedback loop with CaWRKY40 to amplify defense signaling.

    PubMed

    Shen, Lei; Yang, Sheng; Yang, Tong; Liang, Jiaqi; Cheng, Wei; Wen, Jiayu; Liu, Yanyan; Li, Jiazhi; Shi, Lanping; Tang, Qian; Shi, Wei; Hu, Jiong; Liu, Cailing; Zhang, Yangwen; Mou, Shaoliang; Liu, Zhiqin; Cai, Hanyang; He, Li; Guan, Deyi; Wu, Yang; He, Shuilin

    2016-01-01

    CaWRKY40 is a positive regulator of pepper (Capsicum annum) response to Ralstonia solanacearum inoculation (RSI), but the underlying mechanism remains largely unknown. Here, we functionally characterize CaCDPK15 in the defense signaling mediated by CaWRKY40. Pathogen-responsive TGA, W, and ERE boxes were identified in the CaCDPK15 promoter (pCaCDPK15), and pCaCDPK15-driven GUS expression was significantly enhanced in response to RSI and exogenously applied salicylic acid, methyl jasmonate, abscisic acid, and ethephon. Virus-induced gene silencing (VIGS) of CaCDPK15 significantly increased the susceptibility of pepper to RSI and downregulated the immunity-associated markers CaNPR1, CaPR1, and CaDEF1. By contrast, transient CaCDPK15 overexpression significantly activated hypersensitive response associated cell death, upregulated the immunity-associated marker genes, upregulated CaWRKY40 expression, and enriched CaWRKY40 at the promoters of its targets genes. Although CaCDPK15 failed to interact with CaWRKY40, the direct binding of CaWRKY40 to pCaCDPK15 was detected by chromatin immunoprecipitation, which was significantly potentiated by RSI in pepper plants. These combined results suggest that RSI in pepper induces CaCDPK15 and indirectly activates downstream CaWRKY40, which in turn potentiates CaCDPK15 expression. This positive-feedback loop would amplify defense signaling against RSI and efficiently activate strong plant immunity. PMID:26928570

  14. CaCDPK15 positively regulates pepper responses to Ralstonia solanacearum inoculation and forms a positive-feedback loop with CaWRKY40 to amplify defense signaling

    PubMed Central

    Shen, Lei; Yang, Sheng; Yang, Tong; Liang, Jiaqi; Cheng, Wei; Wen, Jiayu; Liu, Yanyan; Li, Jiazhi; Shi, Lanping; Tang, Qian; Shi, Wei; Hu, Jiong; Liu, Cailing; Zhang, Yangwen; Mou, Shaoliang; Liu, Zhiqin; Cai, Hanyang; He, Li; Guan, Deyi; Wu, Yang; He, Shuilin

    2016-01-01

    CaWRKY40 is a positive regulator of pepper (Capsicum annum) response to Ralstonia solanacearum inoculation (RSI), but the underlying mechanism remains largely unknown. Here, we functionally characterize CaCDPK15 in the defense signaling mediated by CaWRKY40. Pathogen-responsive TGA, W, and ERE boxes were identified in the CaCDPK15 promoter (pCaCDPK15), and pCaCDPK15-driven GUS expression was significantly enhanced in response to RSI and exogenously applied salicylic acid, methyl jasmonate, abscisic acid, and ethephon. Virus-induced gene silencing (VIGS) of CaCDPK15 significantly increased the susceptibility of pepper to RSI and downregulated the immunity-associated markers CaNPR1, CaPR1, and CaDEF1. By contrast, transient CaCDPK15 overexpression significantly activated hypersensitive response associated cell death, upregulated the immunity-associated marker genes, upregulated CaWRKY40 expression, and enriched CaWRKY40 at the promoters of its targets genes. Although CaCDPK15 failed to interact with CaWRKY40, the direct binding of CaWRKY40 to pCaCDPK15 was detected by chromatin immunoprecipitation, which was significantly potentiated by RSI in pepper plants. These combined results suggest that RSI in pepper induces CaCDPK15 and indirectly activates downstream CaWRKY40, which in turn potentiates CaCDPK15 expression. This positive-feedback loop would amplify defense signaling against RSI and efficiently activate strong plant immunity. PMID:26928570

  15. On the dynamic forcing of short-term climate fluctuations by feedback mechanisms

    NASA Technical Reports Server (NTRS)

    Reiter, E. R.

    1979-01-01

    Various internal feedback mechanisms in the ocean atmosphere system were studied. A variability pattern of sea surface temperature with a quasibiennial oscillation (QBO) was detected off the coast of Senegal, in the Gulf of Guinea and even in the Gulf Stream as it leaves the North American continental shelf. Possible physical connections between some of these QBO's were pointed out by a hypothetical feedback model. Interaction of a QBO with the annual cycle may lead to beating frequencies resembling climatic trends of a duration of several years.

  16. Positive and negative feedbacks to climate change associated with methane emissions from arctic permafrost systems (Invited)

    NASA Astrophysics Data System (ADS)

    Walter Anthony, K. M.; Grosse, G.; Jones, B. M.

    2009-12-01

    Arctic permafrost contains 950 billion tons of organic carbon (C) in the surface tens of meters, an amount comparable to the current atmospheric CO2 burden of 750 billion tons. This C pool, which accumulated in permafrost over tens of thousands of years, is a threat to global climate because of its vulnerability to rapid microbial decomposition upon thaw, resulting in the release of greenhouse gases CO2 and CH4 to the atmosphere. Greenhouse gas release from thawing permafrost constitutes one of the most important positive feedbacks of terrestrial ecosystems to climate warming in a warmer world. Based on patterns of permafrost degradation during the present interglacial period, estimates of the amount of C remaining in permafrost today, long term field measurements of CH4 and CO2 flux, laboratory incubation experiments, and mass balance calculations of the efficiency of CH4 production from thawed permafrost, we predict that at least 50 billion tons of CH4 (equivalent to 10 times the current atmospheric methane burden) will escape from thermokarst (thaw) lakes in Siberia’s Yedoma Ice Complex as it warms and thaws. Additional CH4 will be released from the remainder of arctic lakes. Under current projections of arctic warming of 7-8 deg C by 2100, widespread permafrost thaw will release 0.1-0.2 billion tons of CH4 yr-1 by 2100, an order of magnitude more than its current source strength, adding another 20-40% of all human and natural sources of CH4 to the atmosphere. Permafrost thaw may lead to an additional source of methane if expanding thaw bulbs beneath lakes and rivers intersect faults and unconsolidated sediments leading to the escape of CH4 from geological sources, such as those recently observed on the North Slope of Alaska with a flux of 60-100 kg CH4 m-2 d-1. Thermokarst lake dynamics play a pivotal role in permafrost degradation and aggradation in the Arctic such that the landscape resembles a palimpsest of lakes and drained lake basins. Analysis of remote

  17. Failure of feedback as a putative common mechanism of spreading depolarizations in migraine and stroke

    NASA Astrophysics Data System (ADS)

    Dahlem, Markus A.; Schneider, Felix M.; Schöll, Eckehard

    2008-06-01

    The stability of cortical function depends critically on proper regulation. Under conditions of migraine and stroke a breakdown of transmembrane chemical gradients can spread through cortical tissue. A concomitant component of this emergent spatio-temporal pattern is a depolarization of cells detected as slow voltage variations. The propagation velocity of ˜3mm/min indicates a contribution of diffusion. We propose a mechanism for spreading depolarizations (SD) that rests upon a nonlocal or noninstantaneous feedback in a reaction-diffusion system. Depending upon the characteristic space and time scales of the feedback, the propagation of cortical SD can be suppressed by shifting the bifurcation line, which separates the parameter regime of pulse propagation from the regime where a local disturbance dies out. The optimization of this feedback is elaborated for different control schemes and ranges of control parameters.

  18. A positive feedback between p53 and miR-34 miRNAs mediates tumor suppression

    PubMed Central

    Okada, Nobuhiro; Lin, Chao-Po; Ribeiro, Marcelo C.; Biton, Anne; Lai, Gregory; He, Xingyue; Bu, Pengcheng; Vogel, Hannes; Jablons, David M.; Keller, Andreas C.; Wilkinson, J. Erby; He, Biao; Speed, Terry P.; He, Lin

    2014-01-01

    As bona fide p53 transcriptional targets, miR-34 microRNAs (miRNAs) exhibit frequent alterations in many human tumor types and elicit multiple p53 downstream effects upon overexpression. Unexpectedly, miR-34 deletion alone fails to impair multiple p53-mediated tumor suppressor effects in mice, possibly due to the considerable redundancy in the p53 pathway. Here, we demonstrate that miR-34a represses HDM4, a potent negative regulator of p53, creating a positive feedback loop acting on p53. In a Kras-induced mouse lung cancer model, miR-34a deficiency alone does not exhibit a strong oncogenic effect. However, miR-34a deficiency strongly promotes tumorigenesis when p53 is haploinsufficient, suggesting that the defective p53–miR-34 feedback loop can enhance oncogenesis in a specific context. The importance of the p53/miR-34/HDM4 feedback loop is further confirmed by an inverse correlation between miR-34 and full-length HDM4 in human lung adenocarcinomas. In addition, human lung adenocarcinomas generate an elevated level of a short HDM4 isoform through alternative polyadenylation. This short HDM4 isoform lacks miR-34-binding sites in the 3′ untranslated region (UTR), thereby evading miR-34 regulation to disable the p53-miR-34 positive feedback. Taken together, our results elucidated the intricate cross-talk between p53 and miR-34 miRNAs and revealed an important tumor suppressor effect generated by this positive feedback loop. PMID:24532687

  19. Positive feedback regulation between adiponectin and T-cadherin impacts adiponectin levels in tissue and plasma of male mice.

    PubMed

    Matsuda, Keisuke; Fujishima, Yuya; Maeda, Norikazu; Mori, Takuya; Hirata, Ayumu; Sekimoto, Ryohei; Tsushima, Yu; Masuda, Shigeki; Yamaoka, Masaya; Inoue, Kana; Nishizawa, Hitoshi; Kita, Shunbun; Ranscht, Barbara; Funahashi, Tohru; Shimomura, Iichiro

    2015-03-01

    Adiponectin (Adipo), a multimeric adipocyte-secreted protein abundant in the circulation, is implicated in cardiovascular protective functions. Recent work documented that Adipo locally associates with responsive tissues through interactions with T-cadherin (Tcad), an atypical, glycosylphosphatidylinositol (GPI)-anchored cadherin cell surface glycoprotein. Mice deficient for Tcad lack tissue-associated Adipo, accumulate Adipo in the circulation, and mimic the Adipo knockout (KO) cardiovascular phenotype. In reverse, Tcad protein is visibly reduced from cardiac tissue in Adipo-KO mice, suggesting interdependent regulation of the 2 proteins. Here, we evaluate the effect of Adipo on Tcad protein expression. Adipo and Tcad proteins were colocalized in aorta, heart, and skeletal muscle. Adipo positively regulated levels of Tcad protein in vivo and in endothelial cell (EC) cultures. In Tcad-KO mice, binding of endogenous and exogenously administered Adipo to cardiovascular tissues was dramatically reduced. Consistently, knockdown of Tcad in cultured murine vascular ECs significantly diminished Adipo binding. In search for a possible mechanism, we found that enzymatic cleavage of Tcad with phosphatidylinositol-specific phospholipase C increases plasma Adipo while decreasing tissue-bound levels. Similarly, pretreatment of cultured ECs with serum containing Adipo attenuated phosphatidylinositol-specific phospholipase C-mediated Tcad cleavage. In vivo administration of adenovirus producing Adipo suppressed plasma levels of GPI phospholipase D, the endogenous cleavage enzyme for GPI-anchored proteins. In conclusion, our data show that both circulating and tissue-bound Adipo levels are dependent on Tcad and, in reverse, regulate tissue Tcad levels through a positive feedback loop that operates by suppressing phospholipase-mediated Tcad release from the cell surface. PMID:25514086

  20. Combined prokaryotic-eukaryotic delivery and expression of therapeutic factors through a primed autocatalytic positive-feedback loop.

    PubMed

    Shi, Lei; Yu, Bin; Cai, Chun-Hui; Huang, Wei; Zheng, Bo-Jian; Smith, David Keith; Huang, Jian-Dong

    2016-01-28

    Progress in bacterial therapy for cancer and infectious diseases is hampered by the absence of safe and efficient vectors. Sustained delivery and high gene expression levels are critical for the therapeutic efficacy. Here we developed a Salmonella typhimrium strain to maintain and safely deliver a plasmid vector to target tissues. This vector is designed to allow dual transcription of therapeutic factors, such as cytotoxic proteins, short hairpin RNAs or combinations, in the nucleus or cytoplasm of eukaryotic cells, with this expression sustained by an autocatalytic positive-feedback loop. Mechanisms to prime the system and maintain the plasmid in the bacterium are also provided. Synergistic effects of attenuated Salmonella and our inter-kingdom system allow the precise expression of Diphtheria toxin A chain (DTA) gene in tumor microenvironment and eradicate large established tumors in immunocompetent animals. In the experiments reported here, 26% of mice (n=5/19) with aggressive tumors were cured and the others all survived until the end of the experiment. We also demonstrated that ST4 packaged with shRNA-encoding plasmids has sustained knockdown effects in nude mice bearing human MDA-MB-231 xenografts. Three weeks after injection of 5×10(6) ST4/pIKT-shPlk, PLK1 transcript levels in tumors were 62.5±18.6% lower than the vector control group (P=0.015). The presence of PLK1 5' RACE-PCR cleavage products confirmed a sustained RNAi-mediated mechanism of action. This innovative technology provides an effective and versatile vehicle for efficient inter-kingdom gene delivery that can be applied to cancer therapy and other purposes. PMID:26682504

  1. Positive feedback produces broad distributions in maximum activation attained within a narrow time window in stochastic biochemical reactions

    NASA Astrophysics Data System (ADS)

    Das, Jayajit

    2013-01-01

    How do single cell fate decisions induced by activation of key signaling proteins above threshold concentrations within a time interval are affected by stochastic fluctuations in biochemical reactions? We address this question using minimal models of stochastic chemical reactions commonly found in cell signaling and gene regulatory systems. Employing exact solutions and semi-analytical methods we calculate distributions of the maximum value (N) of activated species concentrations (Pmax(N)) and the time (t) taken to reach the maximum value (Pmax(t)) within a time interval in the minimal models. We find, the presence of positive feedback interactions make Pmax(N) more spread out with a higher "peakedness" in Pmax(t). Thus positive feedback interactions may help single cells to respond sensitively to a stimulus when cell decision processes require upregulation of activated forms of key proteins to a threshold number within a time window.

  2. Performance Analysis of Positive-feedback-based Active Anti-islanding Schemes for Inverter-Based Distributed Generators

    SciTech Connect

    Du, Pengwei; Aponte, Erick E.; Nelson, J. Keith

    2010-06-14

    Recently proposed positive-feedback-based anti-islanding schemes (AI) are highly effective in preventing islanding without causing any degradation in power quality. This paper aims to analyze the performance of these schemes quantitatively in the context of the dynamic models of inverter-based distributed generators (DG). In this study, the characteristics of these active anti-islanding methods are discussed and design guidelines are derived.

  3. Early Detection of Online Auction Opportunistic Sellers through the Use of Negative-Positive Feedback

    ERIC Educational Resources Information Center

    Reinert, Gregory J.

    2010-01-01

    Apparently fraud is a growth industry. The monetary losses from Internet fraud have increased every year since first officially reported by the Internet Crime Complaint Center (IC3) in 2000. Prior research studies and third-party reports of fraud show rates substantially higher than eBay's reported negative feedback rate of less than 1%. The…

  4. The positive feedback action of vasopressin on its own release from rat septal tissue in vitro is receptor-mediated.

    PubMed

    Landgraf, R; Ramirez, A D; Ramirez, V D

    1991-04-01

    The effect of arginine vasopressin (AVP) on its own septal release was evaluated using an in vitro superfusion procedure. As compared to basal release from septal fragments, pulses of synthetic AVP (15 pg/5 min) resulted in a 25-fold augmented release of endogenous AVP, indicating a positive feedback action. Both the basal and stimulated AVP release were significantly increased by 60 mM potassium and markedly reduced by omission of calcium. Preincubation of the septal fragments with the V2/V1 AVP receptor antagonist d(CH2)5 [D-Tyr (Et)2,Val4]AVP resulted in a dose-dependent inhibition of the positive feedback action of AVP which was nearly completely blocked at doses between 1.25 and 5 ng per 100 microliters incubation medium. As compared to this effect, the V1 antagonist d(CH2)5 Tyr (Me)2 AVP as well as oxytocin were significantly less potent. The results suggest that the positive feedback action of AVP on its own release from septal fragments is potassium-stimulated, calcium-dependent and mainly V2 receptor-mediated. The physiological significance of this phenomenon remains to be shown. PMID:1830507

  5. Low-power feedback-enhanced electro-mechanical impedance (FEMI) sensors

    NASA Astrophysics Data System (ADS)

    Jang, Ji Eun; Yue, C. Patrick

    2008-03-01

    Electro-mechanical impedance (EMI) method utilizing smart piezoelectric sensors has emerged as a promising technology for structural health monitoring in civil, mechanical and aerospace engineering. However, two major limiting factors have prevented field deployment of this method in real life. First, smart piezoelectric sensors, such as Lead Zirconate Titanate (PZT) patches, are highly sensitive to environmental changes such as temperature, humidity, and vibration. Secondly, bulky and expensive equipment is needed for performing impedance measurement. This paper proposes a feedback-enhanced electro-mechanical impedance (FEMI) technique for improving robustness against environmental variations and a design of a low-power EMI sensor with built-in measurement circuitries based on this new technique. The proposed FEMI technique employs a feedback scheme to amplify the peaking characteristics of the natural resonance frequencies in the EMI frequency response. The feedback loop includes a phase-locked loop (PLL) and a transimpedance amplifier (TIA). An analog EMI measurement circuit is developed to replace bulky EMI measurement instruments. To keep the power consumption low, the proposed system does not require any analog-to-digital conversion or DSP circuit blocks, but uses a simple analog mixer to multiply input and output waveforms of the PZT sensor, and then extract the EMI amplitude by passing the mixer output through a low-pass filter (LPF). The performance of the proposed FEMI sensor is verified by simulations using MATLAB. Simulated natural frequency peaks in the EMI spectrum are noticeably sharper with the feedback scheme than the one without feedback. As a result, the natural frequency shift due to any structural change can be more easily detected. To quantify the shift of these natural frequency peaks, the root mean square deviation (RMSD) of the difference between cases with and without damage is calculated. The simulation results show that the RMSD with

  6. 2D tilting MEMS micro mirror integrating a piezoresistive sensor position feedback

    NASA Astrophysics Data System (ADS)

    Lani, S.; Bayat, D.; Despont, M.

    2015-02-01

    An integrated position sensor for a dual-axis electromagnetic tilting mirror is presented. This tilting mirror is composed of a silicon based mirror directly assembled on a silicon membrane supported by flexible beams. The position sensors are constituted by 4 Wheatstone bridges of piezoresistors which are fabricated by doping locally the flexible beams. A permanent magnet is attached to the membrane and the scanner is mounted above planar coils deposited on a ceramic substrate to achieve electromagnetic actuation. The performances of the piezoresistive sensors are evaluated by measuring the output signal of the piezoresistors as a function of the tilt of the mirror and the temperature. White light interferometry was performed for all measurement to measure the exact tilt angle. The minimum detectable angle with such sensors was 30µrad (around 13bits) in the range of the minimum resolution of the interferometer. The tilt reproducibility was 0.0186%, obtained by measuring the tilt after repeated actuations with a coil current of 50mA during 30 min and the stability over time was 0.05% in 1h without actuation. The maximum measured tilt angle was 6° (mechanical) limited by nonlinearity of the MEMS system.

  7. GATA Factor-Dependent Positive-Feedback Circuit in Acute Myeloid Leukemia Cells.

    PubMed

    Katsumura, Koichi R; Ong, Irene M; DeVilbiss, Andrew W; Sanalkumar, Rajendran; Bresnick, Emery H

    2016-08-30

    The master regulatory transcription factor GATA-2 triggers hematopoietic stem and progenitor cell generation. GATA2 haploinsufficiency is implicated in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), and GATA2 overexpression portends a poor prognosis for AML. However, the constituents of the GATA-2-dependent genetic network mediating pathogenesis are unknown. We described a p38-dependent mechanism that phosphorylates GATA-2 and increases GATA-2 target gene activation. We demonstrate that this mechanism establishes a growth-promoting chemokine/cytokine circuit in AML cells. p38/ERK-dependent GATA-2 phosphorylation facilitated positive autoregulation of GATA2 transcription and expression of target genes, including IL1B and CXCL2. IL-1β and CXCL2 enhanced GATA-2 phosphorylation, which increased GATA-2-mediated transcriptional activation. p38/ERK-GATA-2 stimulated AML cell proliferation via CXCL2 induction. As GATA2 mRNA correlated with IL1B and CXCL2 mRNAs in AML-M5 and high expression of these genes predicted poor prognosis of cytogenetically normal AML, we propose that the circuit is functionally important in specific AML contexts. PMID:27545880

  8. Feedback as a mechanism for the resurrection of oscillations from death states

    NASA Astrophysics Data System (ADS)

    Chandrasekar, V. K.; Karthiga, S.; Lakshmanan, M.

    2015-07-01

    The quenching of oscillations in interacting systems leads to several unwanted situations, which necessitate a suitable remedy to overcome the quenching. In this connection, this work addresses a mechanism that can resurrect oscillations in a typical situation. Through both numerical and analytical studies, we show that the candidate which is capable of resurrecting oscillations is nothing but the feedback, the one which is profoundly used in dynamical control and in biotherapies. Even in the case of a rather general system, we demonstrate analytically the applicability of the technique over one of the oscillation quenched states called amplitude death states. We also discuss some of the features of this mechanism such as adaptability of the technique with the feedback of only a few of the oscillators.

  9. 30 CFR 33.23 - Mechanical positioning of parts.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., EVALUATION, AND APPROVAL OF MINING PRODUCTS DUST COLLECTORS FOR USE IN CONNECTION WITH ROCK DRILLING IN COAL MINES Dust-Collector Requirements § 33.23 Mechanical positioning of parts. All parts of a unit that...

  10. 30 CFR 33.23 - Mechanical positioning of parts.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., EVALUATION, AND APPROVAL OF MINING PRODUCTS DUST COLLECTORS FOR USE IN CONNECTION WITH ROCK DRILLING IN COAL MINES Dust-Collector Requirements § 33.23 Mechanical positioning of parts. All parts of a unit that...

  11. 30 CFR 33.23 - Mechanical positioning of parts.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., EVALUATION, AND APPROVAL OF MINING PRODUCTS DUST COLLECTORS FOR USE IN CONNECTION WITH ROCK DRILLING IN COAL MINES Dust-Collector Requirements § 33.23 Mechanical positioning of parts. All parts of a unit that...

  12. Feedback reciprocity mechanism promotes the cooperation of highly clustered scale-free networks

    NASA Astrophysics Data System (ADS)

    Rong, Zhihai; Yang, Han-Xin; Wang, Wen-Xu

    2010-10-01

    We study how the clustering coefficient influences the evolution of cooperation in scale-free public goods games. In games played by groups of individuals, triangle loops provide stronger support for mutual cooperation to resist invasion of selfish behavior than that in the absence of such loops, so that diffusion of cooperative behavior is relatively promoted. The feedback reciprocity mechanism of triangle plays a key role in facilitating cooperation in high clustered networks.

  13. Modeling Discontinuous Phase Transitions in Gel Membranes: Focus on Hysteresis and Feedback Mechanisms

    NASA Astrophysics Data System (ADS)

    Kuksenok, Olga

    Feedback mechanisms are vital in a number of processes in biological systems. For example, feedback loops play an essential role during a limb development in mammals and are responsible for the asymmetric cell division to constrain the growth in plants to the specific regions. An integration of well-controlled feedback loops into the fully synthetic materials is an important step in designing a range of biomimetic functionalities. Herein, we focus on hydrogels functionalized with light-sensitive trisodium salt of copper chlorophyllin and study discontinuous phase transitions in these systems. Prior experimental studies had shown that illumination of these functionalized gels results in their heating and in discontinuous, first order phase transition upon the variation in temperature. Herein, we develop the first computational model for these gels; the framework of the model is based on the gel Lattice Spring Model, in this work we account for the gel heating under the illumination. The results of our simulations are in a good agreement with prior experimental studies. We focus on pattern development during the volume phase transitions in membranes of various thicknesses and show that one can effectively utilize light intensity to remotely control feedback loops in these systems.

  14. A positive feedback loop involving Erk5 and Akt turns on mesangial cell proliferation in response to PDGF.

    PubMed

    Bera, Amit; Das, Falguni; Ghosh-Choudhury, Nandini; Li, Xiaonan; Pal, Sanjay; Gorin, Yves; Kasinath, Balakuntalam S; Abboud, Hanna E; Ghosh Choudhury, Goutam

    2014-06-01

    Platelet-derived growth factor BB and its receptor (PDGFRβ) play a pivotal role in the development of renal glomerular mesangial cells. Their roles in increased mesangial cell proliferation during mesangioproliferative glomerulonephritis have long been noted, but the operating logic of signaling mechanisms regulating these changes remains poorly understood. We examined the role of a recently identified MAPK, Erk5, in this process. PDGF increased the activating phosphorylation of Erk5 and tyrosine phosphorylation of proteins in a time-dependent manner. A pharmacologic inhibitor of Erk5, XMD8-92, abrogated PDGF-induced DNA synthesis and mesangial cell proliferation. Similarly, expression of dominant negative Erk5 or siRNAs against Erk5 blocked PDGF-stimulated DNA synthesis and proliferation. Inhibition of Erk5 attenuated expression of cyclin D1 mRNA and protein, resulting in suppression of CDK4-mediated phosphorylation of the tumor suppressor protein pRb. Expression of cyclin D1 or CDK4 prevented the dominant negative Erk5- or siErk5-mediated inhibition of DNA synthesis and mesangial cell proliferation induced by PDGF. We have previously shown that phosphatidylinositol 3-kinase (PI3-kinase) contributes to PDGF-induced proliferation of mesangial cells. Inhibition of PI3-kinase blocked PDGF-induced phosphorylation of Erk5. Since PI3-kinase acts through Akt, we determined the role of Erk5 on Akt phosphorylation. XMD8-92, dominant negative Erk5, and siErk5 inhibited phosphorylation of Akt by PDGF. Interestingly, we found inhibition of PDGF-induced Erk5 phosphorylation by a pharmacological inhibitor of Akt kinase and kinase dead Akt in mesangial cells. Thus our data unfold the presence of a positive feedback microcircuit between Erk5 and Akt downstream of PI3-kinase nodal point for PDGF-induced mesangial cell proliferation. PMID:24740537

  15. F-actin waves, actin cortex disassembly and focal exocytosis driven by actin-phosphoinositide positive feedback.

    PubMed

    Masters, Thomas A; Sheetz, Michael P; Gauthier, Nils C

    2016-04-01

    Actin polymerization is controlled by the phosphoinositide composition of the plasma membrane. However, the molecular mechanisms underlying the spatiotemporal regulation of actin network organization over extended length scales are still unclear. To observe phosphoinositide-dependent cytoskeletal dynamics we combined the model system of frustrated phagocytosis, total internal reflection microscopy and manipulation of the buffer tonicity. We found that macrophages interacting with IgG-coated glass substrates formed circular F-actin waves on their ventral surface enclosing a region of plasma membrane devoid of cortical actin. Plasma membrane free of actin cortex was strongly depleted of PI(4,5)P2 , but enriched in PI(3,4)P2 and displayed a fivefold increase in exocytosis. Wave formation could be promoted by application of a hypotonic shock. The actin waves were characteristic of a bistable wavefront at the boundary between the regions of membrane containing and lacking cortical actin. Phosphoinositide modifiers and RhoGTPase activities dramatically redistributed with respect to the wavefronts, which often exhibited spatial oscillations. Perturbation of either lipid or actin cytoskeleton-related pathways led to rapid loss of both the polarized lipid distribution and the wavefront. As waves travelled over the plasma membrane, wavefront actin was seen to rapidly polymerize and depolymerize at pre-existing clusters of FcγRIIA, coincident with rapid changes in lipid composition. Thus the potential of receptors to support rapid F-actin polymerization appears to depend acutely on the local concentrations of multiple lipid species. We propose that interdependence through positive feedback from the cytoskeleton to lipid modifiers leads to coordinated local cortex remodeling, focal exocytosis, and organizes extended actin networks. PMID:26915738

  16. Positive feedback regulation of type I IFN production by the IFN-inducible DNA sensor cGAS

    PubMed Central

    Ma, Feng; Li, Bing; Liu, Su-yang; Iyer, Shankar S; Yu, Yongxin; Wu, Aiping; Cheng, Genhong

    2014-01-01

    Rapid and robust induction of type I interferon (IFN-I) is a critical event in host antiviral innate immune response. It has been well demonstrated that cyclic GMP-AMP (cGAMP) synthase (cGAS) plays an important role in sensing cytosolic DNA and triggering stimulator of interferon genes (STING)-dependent signaling to induce IFN-I. However, it is largely unknown how cGAS itself is regulated during pathogen infection and IFN-I production. Here, we show that pattern-recognition receptor (PRR) ligands including lipidA, LPS, polyI:C, polydA:dT, and cGAMP induce cGAS expression in a IFN-I-dependent manner in both mouse and human macrophages. Further experiments indicate that cGAS is an IFN-stimulated gene (ISG), and two adjacent IFN-sensitive response elements (ISREs) in the promoter region of cGAS mediate the induction of cGAS by IFN-I. In addition, we show that optimal production of IFNβ triggered by polydA:dT or HSV-1 requires IFNAR signaling. Knockdown of the constitutively expressed DNA sensor DDX41 attenuates polydA:dT-triggered IFNβ production and cGAS induction. By analyzing the dynamic expression of polydA:dT-induced IFNβ and cGAS transcripts, we have found that induction of IFNβ is earlier than cGAS. Furthermore, we have provided evidence that induction of cGAS by IFN-I meditates the subsequent positive feedback regulation of DNA-triggered IFN-I production. Thus, our study not only provides a novel mechanism of modulating cGAS expression, but also adds another layer of regulation in DNA-triggered IFN-I production by induction of cGAS. PMID:25609843

  17. Reliable Control Using Disturbance Observer and Equivalent Transfer Function for Position Servo System in Current Feedback Loop Failure

    NASA Astrophysics Data System (ADS)

    Ishikawa, Kaoru; Nakamura, Taro; Osumi, Hisashi

    A reliable control method is proposed for multiple loop control system. After a feedback loop failure, such as case of the sensor break down, the control system becomes unstable and has a big fluctuation even if it has a disturbance observer. To cope with this problem, the proposed method uses an equivalent transfer function (ETF) as active redundancy compensation after the loop failure. The ETF is designed so that it does not change the transfer function of the whole system before and after the loop failure. In this paper, the characteristic of reliable control system that uses an ETF and a disturbance observer is examined by the experiment that uses the DC servo motor for the current feedback loop failure in the position servo system.

  18. State transitions and feedback mechanisms control hydrology in the constructed catchment ´Chicken Creeḱ

    NASA Astrophysics Data System (ADS)

    Schaaf, Wolfgang; Gerwin, Werner; Hinz, Christoph; Zaplata, Markus

    2016-04-01

    Landscapes and ecosystems are complex systems with many feedback mechanisms acting between the various abiotic and biotic components. The knowledge about these interacting processes is mainly derived from mature ecosystems. The initial development of ecosystem complexity may involve state transitions following catastrophic shifts, disturbances or transgression of thresholds. The Chicken Creek catchment was constructed in 2005 in the mining area of Lusatia/Germany to study processes and feedback mechanisms during ecosystem evolution. The hillslope-shaped 6 ha site has defined boundary conditions and well-documented inner structures. The dominating substrate above the underlying clay layer is Pleistocene sandy material representing mainly the lower C horizon of the former landscape. Since 2005, the unrestricted, unmanaged development of the catchment was intensively monitored. During the ten years since then, we observed characteristic state transitions in catchment functioning driven by feedbacks between original substrate properties, surface structures, soil development and vegetation succession. Whereas surface runoff induced by surface crusting and infiltration dominated catchment hydrology in the first years, the impact of vegetation on hydrological pathways and groundwater levels became more and more evident during the last years. Discharge from the catchment changed from episodic events driven by precipitation and surface runoff to groundwater driven. This general picture is overlain by spatial patterns and single episodic events of external drivers. The scientific value of the Chicken Creek site with known boundary conditions and structure information could help in disentangling general feedback mechanisms between hydrologic, pedogenic, biological and geomorphological processes as well as a in gaining a more integrative view of succession and its drivers during the transition from initial, less complex systems to more mature ecosystems. Long-term time series

  19. ASSESSING RADIATION PRESSURE AS A FEEDBACK MECHANISM IN STAR-FORMING GALAXIES

    SciTech Connect

    Andrews, Brett H.; Thompson, Todd A.

    2011-02-01

    Radiation pressure from the absorption and scattering of starlight by dust grains may be an important feedback mechanism in regulating star-forming galaxies. We compile data from the literature on star clusters, star-forming subregions, normal star-forming galaxies, and starbursts to assess the importance of radiation pressure on dust as a feedback mechanism, by comparing the luminosity and flux of these systems to their dust Eddington limit. This exercise motivates a novel interpretation of the Schmidt law, the L{sub IR}-L'{sub CO} correlation, and the L{sub IR}-L'{sub HCN} correlation. In particular, the linear L{sub IR}-L'{sub HCN} correlation is a natural prediction of radiation pressure regulated star formation. Overall, we find that the Eddington limit sets a hard upper bound to the luminosity of any star-forming region. Importantly, however, many normal star-forming galaxies have luminosities significantly below the Eddington limit. We explore several explanations for this discrepancy, especially the role of 'intermittency' in normal spirals-the tendency for only a small number of subregions within a galaxy to be actively forming stars at any moment because of the time dependence of the feedback process and the luminosity evolution of the stellar population. If radiation pressure regulates star formation in dense gas, then the gas depletion timescale is 6 Myr, in good agreement with observations of the densest starbursts. Finally, we highlight the importance of observational uncertainties, namely, the dust-to-gas ratio and the CO-to-H{sub 2} and HCN-to-H{sub 2} conversion factors, that must be understood before a definitive assessment of radiation pressure as a feedback mechanism in star-forming galaxies.

  20. Balanced bridge feedback control system

    NASA Technical Reports Server (NTRS)

    Lurie, Boris J. (Inventor)

    1990-01-01

    In a system having a driver, a motor, and a mechanical plant, a multiloop feedback control apparatus for controlling the movement and/or positioning of a mechanical plant, the control apparatus has a first local bridge feedback loop for feeding back a signal representative of a selected ratio of voltage and current at the output driver, and a second bridge feedback loop for feeding back a signal representative of a selected ratio of force and velocity at the output of the motor. The control apparatus may further include an outer loop for feeding back a signal representing the angular velocity and/or position of the mechanical plant.

  1. Force Feedback Controls Motor Activity and Mechanical Properties of Self-Assembling Branched Actin Networks.

    PubMed

    Bieling, Peter; Li, Tai-De; Weichsel, Julian; McGorty, Ryan; Jreij, Pamela; Huang, Bo; Fletcher, Daniel A; Mullins, R Dyche

    2016-01-14

    Branched actin networks--created by the Arp2/3 complex, capping protein, and a nucleation promoting factor--generate and transmit forces required for many cellular processes, but their response to force is poorly understood. To address this, we assembled branched actin networks in vitro from purified components and used simultaneous fluorescence and atomic force microscopy to quantify their molecular composition and material properties under various forces. Remarkably, mechanical loading of these self-assembling materials increases their density, power, and efficiency. Microscopically, increased density reflects increased filament number and altered geometry but no change in average length. Macroscopically, increased density enhances network stiffness and resistance to mechanical failure beyond those of isotropic actin networks. These effects endow branched actin networks with memory of their mechanical history that shapes their material properties and motor activity. This work reveals intrinsic force feedback mechanisms by which mechanical resistance makes self-assembling actin networks stiffer, stronger, and more powerful. PMID:26771487

  2. Construction and Modelling of an Inducible Positive Feedback Loop Stably Integrated in a Mammalian Cell-Line

    PubMed Central

    Siciliano, Velia; Fracassi, Chiara; Garzilli, Immacolata; Moretti, Maria Nicoletta; di Bernardo, Diego

    2011-01-01

    Understanding the relationship between topology and dynamics of transcriptional regulatory networks in mammalian cells is essential to elucidate the biology of complex regulatory and signaling pathways. Here, we characterised, via a synthetic biology approach, a transcriptional positive feedback loop (PFL) by generating a clonal population of mammalian cells (CHO) carrying a stable integration of the construct. The PFL network consists of the Tetracycline-controlled transactivator (tTA), whose expression is regulated by a tTA responsive promoter (CMV-TET), thus giving rise to a positive feedback. The same CMV-TET promoter drives also the expression of a destabilised yellow fluorescent protein (d2EYFP), thus the dynamic behaviour can be followed by time-lapse microscopy. The PFL network was compared to an engineered version of the network lacking the positive feedback loop (NOPFL), by expressing the tTA mRNA from a constitutive promoter. Doxycycline was used to repress tTA activation (switch off), and the resulting changes in fluorescence intensity for both the PFL and NOPFL networks were followed for up to 43 h. We observed a striking difference in the dynamics of the PFL and NOPFL networks. Using non-linear dynamical models, able to recapitulate experimental observations, we demonstrated a link between network topology and network dynamics. Namely, transcriptional positive autoregulation can significantly slow down the “switch off” times, as comparared to the nonautoregulatated system. Doxycycline concentration can modulate the response times of the PFL, whereas the NOPFL always switches off with the same dynamics. Moreover, the PFL can exhibit bistability for a range of Doxycycline concentrations. Since the PFL motif is often found in naturally occurring transcriptional and signaling pathways, we believe our work can be instrumental to characterise their behaviour. PMID:21765813

  3. Entropy Limit and the Cold Feedback Mechanism in Cooling Flow Clusters

    NASA Astrophysics Data System (ADS)

    Soker, Noam

    2008-09-01

    I propose an explanation for the finding that star formation and visible filaments strong in Hα emission in cooling flow clusters occur only if the minimum specific entropy and the radiative cooling time of the intracluster medium (ICM) are below a specific threshold. The explanation is based on the cold feedback mechanism. In this mechanism, the mass accreted by the central black hole originates in nonlinear overdense blobs of gas residing in an extended region of the cooling flow region. I use the criterion that the feedback cycle period must be longer than the radiative cooling time of dense blobs, for large quantities of gas to cool to low temperatures. The falling time of the dense blobs is parameterized by the ratio of the infall velocity to the sound speed. Another parameter is the ratio of the blobs' density to that of the surrounding ICM. By taking the values of the parameters as in previous papers on the cold feedback model, I derive an expression that gives the right value of the entropy threshold. Future studies will have to examine in more detail the role these parameters play, and will have to show that the observed sharp change in the behavior of clusters across the entropy, or radiative cooling time, threshold can be reproduced by the model.

  4. Teachers' Discoursal Strategies in Providing Positive Feedback to Student Responses: A Study of Four English Immersion Teachers in People's Republic of China

    ERIC Educational Resources Information Center

    Pei, Miao

    2012-01-01

    This paper investigates the discoursal strategies of four teachers in providing feedback to student responses in English classrooms in Xi'an, People's Republic of China. The findings indicate that the teachers provide positive feedback for students English learning in various ways, including using the most common strategies such as accepting,…

  5. A Collaborative Approach to Implement Positive Behavior Support Plans for Children with Problem Behaviors: A Comparison of Consultation versus Consultation and Feedback Approach

    ERIC Educational Resources Information Center

    Erbas, Dilek

    2010-01-01

    The purpose of this study is to compare the effectiveness of consultation alone and consultation plus feedback on the proper use of positive behavior support strategies (PBS) on behaviors of three mothers with children with developmental disabilities. Results indicated that consultation plus feedback was more effective than consultation alone…

  6. Positive and negative feedbacks among Amazon land uses, drought, and fire: the drought of 2005

    NASA Astrophysics Data System (ADS)

    Nepstad, D.; Brando, P.; Soares-Filho, B.; Balch, J.; Moutinho, P.

    2006-12-01

    Climate, rural economies, and ecosystems are connected in the Amazon basin through complex interactions with important implications for greenhouse gas fluxes, biodiversity, and the well-being of rural people. In the historically severe drought of 2005, drought-induced tree mortality and fire-dependent land uses (cattle ranching, swidden agriculture) favored forest fire as it increased the likelihood of further drought. Regions with fire-sensitive investments in the landscape, including improved cattle forage, agroforestry systems, and forest management, were also regions of high investments in the prevention of accidental fire, and experienced low levels of forest fire, in a negative feedback cycle. Some areas of agroindustrial production(cultivated soy) also experienced low forest fire occurrence because of the low flammability of crop fields. The combination of drought- and fire-induced carbon emissions can approach one billion tons in years of severe drought. The negative feedbacks between some types of land use and forest fire could substantially reduce these emissions in the short term.

  7. Essential role of Bmp signaling and its positive feedback loop in the early cell fate evolution of chordates.

    PubMed

    Kozmikova, Iryna; Candiani, Simona; Fabian, Peter; Gurska, Daniela; Kozmik, Zbynek

    2013-10-15

    In chordates, early separation of cell fate domains occurs prior to the final specification of ectoderm to neural and non-neural as well as mesoderm to dorsal and ventral during development. Maintaining such division with the establishment of an exact border between the domains is required for the formation of highly differentiated structures such as neural tube and notochord. We hypothesized that the key condition for efficient cell fate separation in a chordate embryo is the presence of a positive feedback loop for Bmp signaling within the gene regulatory network (GRN), underlying early axial patterning. Here, we therefore investigated the role of Bmp signaling in axial cell fate determination in amphioxus, the basal chordate possessing a centralized nervous system. Pharmacological inhibition of Bmp signaling induces dorsalization of amphioxus embryos and expansion of neural plate markers, which is consistent with an ancestral role of Bmp signaling in chordate axial patterning and neural plate formation. Furthermore, we provided evidence for the presence of the positive feedback loop within the Bmp signaling network of amphioxus. Using mRNA microinjections we found that, in contrast to vertebrate Vent genes, which promote the expression of Bmp4, amphioxus Vent1 is likely not responsible for activation of cephalochordate ortholog Bmp2/4. Cis-regulatory analysis of amphioxus Bmp2/4, Admp and Chordin promoters in medaka embryos revealed remarkable conservation of the gene regulatory information between vertebrates and basal chordates. Our data suggest that emergence of a positive feedback loop within the Bmp signaling network may represent a key molecular event in the evolutionary history of the chordate cell fate determination. PMID:23933491

  8. A Mechanism for Land-Atmosphere Feedback Involving Planetary Wave Structures

    NASA Technical Reports Server (NTRS)

    Koster, Randal D.; Chang, Yehui; Schubert, Siegfried D.

    2014-01-01

    While the ability of land surface conditions to influence the atmosphere has been demonstrated in various modeling and observational studies, the precise mechanisms by which land-atmosphere feedback occurs are still largely unknown particularly the mechanisms that allow land moisture state in one region to affect atmospheric conditions in another. Such remote impacts are examined here in the context of atmospheric general circulation model (AGCM) simulations, leading to the identification of one potential mechanism: the phase-locking and amplification of a planetary wave through the imposition of a spatial pattern of soil moisture at the land surface. This mechanism, shown here to be relevant in the AGCM, apparently also operates in nature, as suggested by supporting evidence found in reanalysis data.

  9. Analysis of Links Positions in Landing Gear Mechanism

    NASA Astrophysics Data System (ADS)

    Brewczyński, D.; Tora, G.

    2014-08-01

    This article contains a kinematic analysis of an aircraft chassis mechanism in a range of positions. The mechanism of the chassis is made up of several smaller subsystems with different functions. The first mechanism is used to eject the chassis before landing (touchdown) and fold it to hatchway after the lift off. The second mechanism is designed to perform rotation of the crossover with the wheel, in order to adjust the position of the wheel to fit it in the limited space in the hold. The third mechanism allows movement of the chassis resulting from the change in length of the damper. To determine the position of the following links of the mechanism calculus of vectors was applied in which unit vectors were used to represent the angular position of the links. The aim of the analysis is to determine the angle of convergence and the angle of heel wheels as a function of the variable length of hydraulic cylinder, length of the shock absorber, length of the regulations rods

  10. Design of a High Resolution Hexapod Positioning Mechanism

    NASA Technical Reports Server (NTRS)

    Britt, Jamie

    2001-01-01

    This paper describes the development of a high resolution, six-degree of freedom positioning mechanism. This mechanism, based on the Stewart platform concept, was designed for use with the Developmental Comparative Active Optics Telescope Testbed (DCATT), a ground-based technology testbed for the Next Generation Space Telescope (NGST). The mechanism provides active control to the DCATT telescope's segmented primary mirror. Emphasis is on design decisions and technical challenges. Significant issues include undesirable motion properties of PZT-inchworm actuators, testing difficulties, dimensional stability, and use of advanced composite materials. Supporting test data from prototype mechanisms is presented.

  11. Design of a High Resolution Hexapod Positioning Mechanism

    NASA Technical Reports Server (NTRS)

    Britt, Jamie; Brodeur, Stephen J. (Technical Monitor)

    2001-01-01

    This paper describes the development of a high resolution, six-degree of freedom positioning mechanism. This mechanism, based on the Stewart platform concept, was designed for use with the Developmental Comparative Active Optics Telescope Testbed (DCATT), a ground-based technology testbed for the Next Generation Space Telescope (NGST). The mechanism provides active control to the DCATT telescope's segmented primary mirror. Emphasis is on design decisions and technical challenges. Significant issues include undesirable motion properties of PZT-inchworm actuators, testing difficulties, dimensional stability and use of advanced composite materials. Supporting test data from prototype mechanisms is presented.

  12. A satellite digital controller or 'play that PID tune again, Sam'. [Position, Integral, Derivative feedback control algorithm for design strategy

    NASA Technical Reports Server (NTRS)

    Seltzer, S. M.

    1976-01-01

    The problem discussed is to design a digital controller for a typical satellite. The controlled plant is considered to be a rigid body acting in a plane. The controller is assumed to be a digital computer which, when combined with the proposed control algorithm, can be represented as a sampled-data system. The objective is to present a design strategy and technique for selecting numerical values for the control gains (assuming position, integral, and derivative feedback) and the sample rate. The technique is based on the parameter plane method and requires that the system be amenable to z-transform analysis.

  13. Visual feedback of the non-moving limb improves active joint-position sense of the impaired limb in Spastic Hemiparetic Cerebral Palsy.

    PubMed

    Smorenburg, Ana R P; Ledebt, Annick; Deconinck, Frederik J A; Savelsbergh, Geert J P

    2011-01-01

    This study examined the active joint-position sense in children with Spastic Hemiparetic Cerebral Palsy (SHCP) and the effect of static visual feedback and static mirror visual feedback, of the non-moving limb, on the joint-position sense. Participants were asked to match the position of one upper limb with that of the contralateral limb. The task was performed in three visual conditions: without visual feedback (no vision); with visual feedback of the non-moving limb (screen); and with visual feedback of the non-moving limb and its mirror reflection (mirror). In addition to the proprioceptive measure, a functional test [Quality of Upper Extremity Skills Test (QUEST)] was performed and the amount of spasticity was determined in order to examine their relation with proprioceptive ability. The accuracy of matching was significantly influenced by the distance that had to be covered by the matching limb; a larger distance resulted in a lower matching accuracy. Moreover it was demonstrated that static (mirror) visual feedback improved the matching accuracy. A clear relation between functionality, as measured by the QUEST, and active joint-position sense was not found. This might be explained by the availability of visual information during the performance of the QUEST. It is concluded that static visual feedback improves matching accuracy in children with SHCP and that the initial distance between the limbs is an influential factor which has to be taken into account when measuring joint-position sense. PMID:21306868

  14. A brain mechanism for facilitation of insight by positive affect.

    PubMed

    Subramaniam, Karuna; Kounios, John; Parrish, Todd B; Jung-Beeman, Mark

    2009-03-01

    Previous research has shown that people solve insight or creative problems better when in a positive mood (assessed or induced), although the precise mechanisms and neural substrates of this facilitation remain unclear. We assessed mood and personality variables in 79 participants before they attempted to solve problems that can be solved by either an insight or an analytic strategy. Participants higher in positive mood solved more problems, and specifically more with insight, compared with participants lower in positive mood. fMRI was performed on 27 of the participants while they solved problems. Positive mood (and to a lesser extent and in the opposite direction, anxiety) was associated with changes in brain activity during a preparatory interval preceding each solved problem; modulation of preparatory activity in several areas biased people to solve either with insight or analytically. Analyses examined whether (a) positive mood modulated activity in brain areas showing responsivity during preparation; (b) positive mood modulated activity in areas showing stronger activity for insight than noninsight trials either during preparation or solution; and (c) insight effects occurred in areas that showed mood-related effects during preparation. Across three analyses, the ACC showed sensitivity to both mood and insight, demonstrating that positive mood alters preparatory activity in ACC, biasing participants to engage in processing conducive to insight solving. This result suggests that positive mood enhances insight, at least in part, by modulating attention and cognitive control mechanisms via ACC, perhaps enhancing sensitivity to detect non-prepotent solution candidates. PMID:18578603

  15. Positive water vapour feedback in climate models confirmed by satellite data

    NASA Technical Reports Server (NTRS)

    Rind, D.; Lerner, J.; Chiou, E.-W.; Chu, W.; Larsen, J.; Mccormick, M. P.; Mcmaster, L.

    1991-01-01

    It has recently been suggested that GCMs used to evaluate climate change overestimate the greenhouse effect due to increased concentrations of trace gases in the atmosphere. Here, new satellite-generated water vapor data are used to compare summer and winter moisture values in regions of the middle and upper troposphere that have previously been difficult to observe with confidence. It is found that, as the hemispheres warm, increased convection leads to increased water vapor above 500 mbar in approximate quantitative agreement with results from current climate models. The same conclusion is reached by comparing the tropical western and eastern Pacific regions. Thus, water vapor feedback is not overestimated in models and should amplify the climate response to increased trace-gas concentrations.

  16. Simultaneous positive and negative external mechanical work in human walking.

    PubMed

    Donelan, J Maxwell; Kram, Rodger; Kuo, Arthur D

    2002-01-01

    In human walking, the center of mass motion is similar to an inverted pendulum. Viewing double support as a transition from one inverted pendulum to the next, we hypothesized that the leading leg performs negative work to redirect the center of mass velocity, while simultaneously, the trailing leg performs positive work to replace the lost energy. To test this hypothesis, we developed a method to quantify the external mechanical work performed by each limb (individual limbs method). Traditional measures of external mechanical work use the sum of the ground reaction forces acting on the limbs (combined limbs method) allowing for the mathematical cancellation of simultaneous positive and negative work during multiple support periods. We expected to find that the traditional combined limbs method underestimates external mechanical work by a substantial amount. We used both methods to measure the external mechanical work performed by humans walking over a range of speeds. We found that during double support, the legs perform a substantial amount of positive and negative external work simultaneously. The combined limbs measures of positive and negative external work were approximately 33% less than those calculated using the individual limbs method. At all speeds, the trailing leg performs greater than 97% of the double support positive work while the leading leg performs greater than 94% of the double support negative work. PMID:11747890

  17. X-ray emission of post-starburst galaxies: looking into the feedback mechanism

    NASA Astrophysics Data System (ADS)

    Ballo, Lucia

    2011-11-01

    The tight relation between galaxy bulges and black holes shows that star formation and accretion must have co-evolved throughout the history of the Universe. The leading hypothesis is that intense periods of star formation and black hole growth concurrently occur in the history of massive galaxies, possibly triggered by mergers. The feedback from the AGN could terminate the star formation and, eventually, extinguish the AGN itself. The complex physics involved in such a scenario is, however, poorly understood. The best class of objects to investigate the relative time-scales of this feedback are the post-starburst galaxies, i.e. galaxies observed shortly after the star-formation has ended (about 0.1-1 Gyr). ~0.3% of the SDSS galaxies in the local Universe show evidence in the optical band of the presence of both a nucleus still accreting in their centre and a post-starburst signature. This suggests that the switching off for a starburst event occurs before the extinguishing of the nuclear activity. However, it is not clear whether this result is a common law in the feedback mechanisms. Here we present a project devoted to study the X-ray emission of the apparently quiescent post-starburst galaxies detected in the SDSS, to deeply investigate the real lack of nuclear activity (possibly obscured in the optical band), and to study the energetics of these systems.

  18. Feedback mechanisms control coexistence in a stem cell model of acute myeloid leukaemia.

    PubMed

    Crowell, Helena L; MacLean, Adam L; Stumpf, Michael P H

    2016-07-21

    Haematopoietic stem cell dynamics regulate healthy blood cell production and are disrupted during leukaemia. Competition models of cellular species help to elucidate stem cell dynamics in the bone marrow microenvironment (or niche), and to determine how these dynamics impact leukaemia progression. Here we develop two models that target acute myeloid leukaemia with particular focus on the mechanisms that control proliferation via feedback signalling. It is within regions of parameter space permissive of coexistence that the effects of competition are most subtle and the clinical outcome least certain. Steady state and linear stability analyses identify parameter regions that allow for coexistence to occur, and allow us to characterise behaviour near critical points. Where analytical expressions are no longer informative, we proceed statistically and sample parameter space over a coexistence region. We find that the rates of proliferation and differentiation of healthy progenitors exert key control over coexistence. We also show that inclusion of a regulatory feedback onto progenitor cells promotes healthy haematopoiesis at the expense of leukaemia, and that - somewhat paradoxically - within the coexistence region feedback increases the sensitivity of the system to dominance by one lineage over another. PMID:27130539

  19. Modeling the relativistic runaway electron avalanche and the feedback mechanism with GEANT4

    PubMed Central

    Skeltved, Alexander Broberg; Østgaard, Nikolai; Carlson, Brant; Gjesteland, Thomas; Celestin, Sebastien

    2014-01-01

    This paper presents the first study that uses the GEometry ANd Tracking 4 (GEANT4) toolkit to do quantitative comparisons with other modeling results related to the production of terrestrial gamma ray flashes and high-energy particle emission from thunderstorms. We will study the relativistic runaway electron avalanche (RREA) and the relativistic feedback process, as well as the production of bremsstrahlung photons from runaway electrons. The Monte Carlo simulations take into account the effects of electron ionization, electron by electron (Møller), and electron by positron (Bhabha) scattering as well as the bremsstrahlung process and pair production, in the 250 eV to 100 GeV energy range. Our results indicate that the multiplication of electrons during the development of RREAs and under the influence of feedback are consistent with previous estimates. This is important to validate GEANT4 as a tool to model RREAs and feedback in homogeneous electric fields. We also determine the ratio of bremsstrahlung photons to energetic electrons Nγ/Ne. We then show that the ratio has a dependence on the electric field, which can be expressed by the avalanche time τ(E) and the bremsstrahlung coefficient α(ε). In addition, we present comparisons of GEANT4 simulations performed with a “standard” and a “low-energy” physics list both validated in the 1 keV to 100 GeV energy range. This comparison shows that the choice of physics list used in GEANT4 simulations has a significant effect on the results. Key Points Testing the feedback mechanism with GEANT4 Validating the GEANT4 programming toolkit Study the ratio of bremsstrahlung photons to electrons at TGF source altitude PMID:26167437

  20. Aging and emotional memory: cognitive mechanisms underlying the positivity effect.

    PubMed

    Spaniol, Julia; Voss, Andreas; Grady, Cheryl L

    2008-12-01

    Younger adults tend to remember negative information better than positive or neutral information (negativity bias). The negativity bias is reduced in aging, with older adults occasionally exhibiting superior memory for positive, as opposed to negative or neutral, information (positivity bias). Two experiments with younger (N=24 in Experiment 1, N=25 in Experiment 2; age range: 18-35 years) and older adults (N=24 in both experiments; age range: 60-85 years) investigated the cognitive mechanisms responsible for age-related differences in recognition memory for emotional information. Results from diffusion model analyses (R. Ratcliff, 1978) indicated that the effects of valence on response bias were similar in both age groups but that Age x Valence interactions emerged in memory retrieval. Specifically, older adults experienced greater overall familiarity for positive items than younger adults. We interpret this finding in terms of an age-related increase in the accessibility of positive information in long-term memory. PMID:19140656

  1. Negative Feedback of Glycolysis and Oxidative Phosphorylation: Mechanisms of and Reasons for It.

    PubMed

    Sokolov, S S; Balakireva, A V; Markova, O V; Severin, F F

    2015-05-01

    There are two main pathways of ATP biosynthesis: glycolysis and oxidative phosphorylation. As a rule, the two pathways are not fully active in a single cell. In this review, we discuss mechanisms of glycolytic inhibition of respiration (Warburg and Crabtree effects). What are the reasons for the existence of this negative feedback? It is known that maximal activation of both processes can cause generation of reactive oxygen species. Oxidative phosphorylation is more efficient from the energy point of view, while glycolysis is safer and favors biomass synthesis. This might be the reason why quiescent cells are mainly using oxidative phosphorylation, while the quickly proliferating ones - glycolysis. PMID:26071773

  2. Role of the Qinghai-Xizang plateau in feedback mechanisms affecting the planetary circulation

    SciTech Connect

    Reiter, E.R.; Yi-Hui, D.

    1980-01-01

    It has been recognized for some time that the Qinghai-Xizang plateau is of great importance in generating planetary long-waves which, in resonance with similar waves induced by the Rocky Mountains, lead to the familiar pattern of quasi-stationary Rossby waves observed on monthly-mean upper level pressure charts. Seasonal forcing of flow patterns also appears to be particularly strong in the Qinghai-Xizang plateau region. Recent investigations suggest that the Qinghai-Xizang plateau may also be involved in feedback mechanisms which control in an important way the interannual variability of the general circulation of the atmosphere. It appears that the effects of the Qinghai-Xizang plateau on the interannual variability of the atmospheric circulation over Asia are but one important manifestation of a network of feedback mechanisms, ranging from the El Nino problems along the Peruvian coast to droughts in the Sahel region. A better understanding of each of the mechanisms involved will lead us closer to successful long-range forecasting of some of the weather phenomena which have a considerable effect on local and regional economics.

  3. The Evolution of Different Forms of Sociality: Behavioral Mechanisms and Eco-Evolutionary Feedback

    PubMed Central

    van der Post, Daniel J.; Verbrugge, Rineke; Hemelrijk, Charlotte K.

    2015-01-01

    Different forms of sociality have evolved via unique evolutionary trajectories. However, it remains unknown to what extent trajectories of social evolution depend on the specific characteristics of different species. Our approach to studying such trajectories is to use evolutionary case-studies, so that we can investigate how grouping co-evolves with a multitude of individual characteristics. Here we focus on anti-predator vigilance and foraging. We use an individual-based model, where behavioral mechanisms are specified, and costs and benefits are not predefined. We show that evolutionary changes in grouping alter selection pressures on vigilance, and vice versa. This eco-evolutionary feedback generates an evolutionary progression from “leader-follower” societies to “fission-fusion” societies, where cooperative vigilance in groups is maintained via a balance between within- and between-group selection. Group-level selection is generated from an assortment that arises spontaneously when vigilant and non-vigilant foragers have different grouping tendencies. The evolutionary maintenance of small groups, and cooperative vigilance in those groups, is therefore achieved simultaneously. The evolutionary phases, and the transitions between them, depend strongly on behavioral mechanisms. Thus, integrating behavioral mechanisms and eco-evolutionary feedback is critical for understanding what kinds of intermediate stages are involved during the evolution of particular forms of sociality. PMID:25629313

  4. The evolution of different forms of sociality: behavioral mechanisms and eco-evolutionary feedback.

    PubMed

    van der Post, Daniel J; Verbrugge, Rineke; Hemelrijk, Charlotte K

    2015-01-01

    Different forms of sociality have evolved via unique evolutionary trajectories. However, it remains unknown to what extent trajectories of social evolution depend on the specific characteristics of different species. Our approach to studying such trajectories is to use evolutionary case-studies, so that we can investigate how grouping co-evolves with a multitude of individual characteristics. Here we focus on anti-predator vigilance and foraging. We use an individual-based model, where behavioral mechanisms are specified, and costs and benefits are not predefined. We show that evolutionary changes in grouping alter selection pressures on vigilance, and vice versa. This eco-evolutionary feedback generates an evolutionary progression from "leader-follower" societies to "fission-fusion" societies, where cooperative vigilance in groups is maintained via a balance between within- and between-group selection. Group-level selection is generated from an assortment that arises spontaneously when vigilant and non-vigilant foragers have different grouping tendencies. The evolutionary maintenance of small groups, and cooperative vigilance in those groups, is therefore achieved simultaneously. The evolutionary phases, and the transitions between them, depend strongly on behavioral mechanisms. Thus, integrating behavioral mechanisms and eco-evolutionary feedback is critical for understanding what kinds of intermediate stages are involved during the evolution of particular forms of sociality. PMID:25629313

  5. Positive feedback produces broad distributions in maximum activation attained within a narrow time window in stochastic biochemical reactions

    NASA Astrophysics Data System (ADS)

    Das, Jayajit

    2013-03-01

    Stochastic fluctuations in biochemical reactions can regulate single cell decision processes. Using exact solutions and semi-analytical methods we calculate distributions of the maximum value (N) of species concentrations (Pmax (N)) and the time (t) taken to reach the maximum value (Pmax (t)) in minimal models of stochastic chemical reactions commonly found in cell signaling systems. We find, the presence of positive feedback interactions make Pmax (N) more spread out with a higher ``peakedness'' in Pmax (t) . Thus positive feedback interactions may help single cells to respond sensitively to a stimulus when cell decision processes require upregulation of activated forms of key proteins to a threshold number within a time window. Moreover, unlike other models of strongly correlated random variables such as Brownian walks or fluctuating interfaces, the extreme value distributions for the chemical reactions display multiscaling behavior emphasizing the presence of many time scales in cell signaling kinetics. This work was funded by the Research Institute at the Nationwide Children's Hospital and a grant (1R56AI090115-01A1) from the NIH.

  6. Positive feedback promotes mitotic exit via the APC/C-Cdh1-separase-Cdc14 axis in budding yeast.

    PubMed

    Hatano, Yuhki; Naoki, Koike; Suzuki, Asuka; Ushimaru, Takashi

    2016-10-01

    The mitotic inhibitor securin is degraded via the ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C)-Cdc20 after anaphase onset. This triggers activation of the mitotic protease separase and thereby sister chromatid separation. However, only a proportion of securin molecules are degraded at metaphase-anaphase transition and the remaining molecules are still present in anaphase. The roles of securin and separase in late mitosis remain elusive. Here, we show that securin still inhibits separase to repress mitotic exit in anaphase in budding yeast. APC/C-Cdh1-mediated securin degradation at telophase further liberated separase, which promotes Cdc14 release and mitotic exit. Separase executed these events via its proteolytic action and that in the Cdc14 early release (FEAR) network. Cdc14 release further activated APC/C-Cdh1 in the manner of a positive feedback loop. Thus, the positive feedback promotes mitotic exit via the APC/C-Cdh1-separase-Cdc14 axis. This study shows the importance of the two-step degradation mode of securin and the role of separase in mitotic exit. PMID:27418100

  7. Hyperosmotic Shock Engages Two Positive Feedback Loops through Caspase-3-dependent Proteolysis of JNK1-2 and Bid.

    PubMed

    Yue, Jicheng; Ben Messaoud, Nabil; López, José M

    2015-12-18

    Hyperosmotic shock induces early calpain activation, Smac/DIABLO release from the mitochondria, and p38/JNK activation in Xenopus oocytes. These pathways regulate late cytochrome c release and caspase-3 activation. Here, we show that JNK1-1 and JNK1-2 are activated early by osmostress, and sustained activation of both isoforms accelerates the apoptotic program. When caspase-3 is activated, JNK1-2 is proteolyzed at Asp-385 increasing the release of cytochrome c and caspase-3 activity, thereby creating a positive feedback loop. Expression of Bcl-xL markedly reduces hyperosmotic shock-induced apoptosis. In contrast, expression of Bid induces rapid caspase-3 activation, even in the absence of osmostress, which is blocked by Bcl-xL co-expression. In these conditions a significant amount of Bid in the cytosol is mono- and bi-ubiquitinated. Caspase-3 activation by hyperosmotic shock induces proteolysis of Bid and mono-ubiquitinated Bid at Asp-52 increasing the release of cytochrome c and caspase-3 activation, and thus creating a second positive feedback loop. Revealing the JNK isoforms and the loops activated by osmostress could help to design better treatments for human diseases caused by perturbations in fluid osmolarity. PMID:26511318

  8. 30 CFR 33.23 - Mechanical positioning of parts.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Mechanical positioning of parts. 33.23 Section 33.23 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS DUST COLLECTORS FOR USE IN CONNECTION WITH ROCK DRILLING IN...

  9. 30 CFR 33.23 - Mechanical positioning of parts.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Mechanical positioning of parts. 33.23 Section 33.23 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS DUST COLLECTORS FOR USE IN CONNECTION WITH ROCK DRILLING IN...

  10. A Cell-Regulatory Mechanism Involving Feedback between Contraction and Tissue Formation Guides Wound Healing Progression

    PubMed Central

    Valero, Clara; Javierre, Etelvina; García-Aznar, José Manuel; Gómez-Benito, María José

    2014-01-01

    Wound healing is a process driven by cells. The ability of cells to sense mechanical stimuli from the extracellular matrix that surrounds them is used to regulate the forces that cells exert on the tissue. Stresses exerted by cells play a central role in wound contraction and have been broadly modelled. Traditionally, these stresses are assumed to be dependent on variables such as the extracellular matrix and cell or collagen densities. However, we postulate that cells are able to regulate the healing process through a mechanosensing mechanism regulated by the contraction that they exert. We propose that cells adjust the contraction level to determine the tissue functions regulating all main activities, such as proliferation, differentiation and matrix production. Hence, a closed-regulatory feedback loop is proposed between contraction and tissue formation. The model consists of a system of partial differential equations that simulates the evolution of fibroblasts, myofibroblasts, collagen and a generic growth factor, as well as the deformation of the extracellular matrix. This model is able to predict the wound healing outcome without requiring the addition of phenomenological laws to describe the time-dependent contraction evolution. We have reproduced two in vivo experiments to evaluate the predictive capacity of the model, and we conclude that there is feedback between the level of cell contraction and the tissue regenerated in the wound. PMID:24681636

  11. Positional Reproducibility of Pancreatic Tumors Under End-Exhalation Breath-Hold Conditions Using a Visual Feedback Technique

    SciTech Connect

    Nakamura, Mitsuhiro; Shibuya, Keiko; Shiinoki, Takehiro; Matsuo, Yukinori; Nakamura, Akira; Nakata, Manabu; Sawada, Akira; Mizowaki, Takashi; Hiraoka, Masahiro

    2011-04-01

    Purpose: To assess positional reproducibility of pancreatic tumors under end-exhalation (EE) breath-hold (BH) conditions with a visual feedback technique based on computed tomography (CT) images. Methods and Materials: Ten patients with pancreatic cancer were enrolled in an institutional review board-approved trial. All patients were placed in a supine position on an individualized vacuum pillow with both arms raised. At the time of CT scan, they held their breath at EE with the aid of video goggles displaying their abdominal displacement. Each three-consecutive helical CT data set was acquired four times (sessions 1-4; session 1 corresponded to the time of CT simulation). The point of interest within or in proximity to a gross tumor volume was defined based on certain structural features. The positional variations in point of interest and margin size required to cover positional variations were assessed. Results: The means {+-} standard deviations (SDs) of intrafraction positional variations were 0.0 {+-} 1.1, 0.1 {+-} 1.2, and 0.1 {+-} 1.0 mm in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions, respectively (p = 0.726). The means {+-} SDs of interfraction positional variations were 0.3 {+-} 2.0, 0.8 {+-} 1.8, and 0.3 {+-} 1.8 mm in the LR, AP, and SI directions, respectively (p = 0.533). Population-based margin sizes required to cover 95th percentiles of the overall positional variations were 4.7, 5.3, and 4.9 mm in the LR, AP, and SI directions, respectively. Conclusions: A margin size of 5 mm was needed to cover the 95th percentiles of the overall positional variations under EE-BH conditions, using this noninvasive approach to motion management for pancreatic tumors.

  12. Optical position feedback of quasi-static 2D MOEMS mirrors

    NASA Astrophysics Data System (ADS)

    Tortschanoff, A.; Baumgart, M.; Holzmann, D.; Lenzhofer, M.; Sandner, T.; Kenda, A.

    2013-05-01

    Recently, we have realized a new position sensing device for MOEMS mirrors applicable to arbitrary trajectories, which is based on the measurement of a reflected light beam with a quadrant diode. In this work we present the characteristics of this device, showing first experimental results obtained with a test set-up, but also theoretical considerations and optical ray-tracing simulations.

  13. Perception of electrical and mechanical stimulation of the skin: implications for electrotactile feedback

    NASA Astrophysics Data System (ADS)

    Marcus, Patrick L.; Fuglevand, Andrew J.

    2009-12-01

    Spinal cord injury is often accompanied by impaired tactile and proprioceptive sensations. Normally, somatosensensory information derived from such sensations is important in the formation of voluntary motor commands. Therefore, as a preliminary step toward the development of an electrotactile feedback system to restore somatosensation, psychophysical methods were used to characterize perceptual attributes associated with electrical stimulation of the skin on the back of the neck in human subjects. These data were compared to mechanical stimulation of the skin on the back of neck and on the distal pad of the index finger. Spatial acuity of the neck, evaluated using two-point thresholds, was not significantly different for electrical (37 ± 14 mm) or mechanical stimulation (39 ± 10 mm). The exponent (β) of the best fitting power function relating perceived intensity to applied stimulus strength was used to characterize perceptual sensitivity to mechanical and electrical stimuli. For electrical stimuli, both current amplitude-modulated and frequency-modulated trains of pulses were tested. Perceptual sensitivity was significantly greater for current amplitude modulation (β = 1.14 ± 0.37) compared to frequency modulation (β = 0.57 ± 0.24) and mechanical stimulation (0.51 ± 0.12). Finally, based on the data gathered here, we derive a transfer function that could be used in the future to convert mechanical stimuli detected with artificial sensors placed on the fingers into electrotactile signals that evoke perceptions similar to those arising from normal mechanical stimulation of the skin.

  14. A protonation-coupled feedback mechanism controls the signalling process in bathy phytochromes

    NASA Astrophysics Data System (ADS)

    Velazquez Escobar, Francisco; Piwowarski, Patrick; Salewski, Johannes; Michael, Norbert; Fernandez Lopez, Maria; Rupp, Anna; Muhammad Qureshi, Bilal; Scheerer, Patrick; Bartl, Franz; Frankenberg-Dinkel, Nicole; Siebert, Friedrich; Andrea Mroginski, Maria; Hildebrandt, Peter

    2015-05-01

    Phytochromes are bimodal photoswitches composed of a photosensor and an output module. Photoactivation of the sensor is initiated by a double bond isomerization of the tetrapyrrole chromophore and eventually leads to protein conformational changes. Recently determined structural models of phytochromes identify differences between the inactive and the signalling state but do not reveal the mechanism of photosensor activation or deactivation. Here, we report a vibrational spectroscopic study on bathy phytochromes that demonstrates that the formation of the photoactivated state and thus (de)activation of the output module is based on proton translocations in the chromophore pocket coupling chromophore and protein structural changes. These proton transfer steps, involving the tetrapyrrole and a nearby histidine, also enable thermal back-isomerization of the chromophore via keto-enol tautomerization to afford the initial dark state. Thus, the same proton re-arrangements inducing the (de)activation of the output module simultaneously initiate the reversal of this process, corresponding to a negative feedback mechanism.

  15. RADIATIVE AND MOMENTUM-BASED MECHANICAL ACTIVE GALACTIC NUCLEUS FEEDBACK IN A THREE-DIMENSIONAL GALAXY EVOLUTION CODE

    SciTech Connect

    Choi, Ena; Ostriker, Jeremiah P.; Naab, Thorsten; Johansson, Peter H.

    2012-08-01

    We study the growth of black holes (BHs) in galaxies using three-dimensional smoothed particle hydrodynamic simulations with new implementations of the momentum mechanical feedback, and restriction of accreted elements to those that are gravitationally bound to the BH. We also include the feedback from the X-ray radiation emitted by the BH, which heats the surrounding gas in the host galaxies, and adds radial momentum to the fluid. We perform simulations of isolated galaxies and merging galaxies and test various feedback models with the new treatment of the Bondi radius criterion. We find that overall the BH growth is similar to what has been obtained by earlier works using the Springel, Di Matteo, and Hernquist algorithms. However, the outflowing wind velocities and mechanical energy emitted by winds are considerably higher (v{sub w} {approx} 1000-3000 km s{sup -1}) compared to the standard thermal feedback model (v{sub w} {approx} 50-100 km s{sup -1}). While the thermal feedback model emits only 0.1% of BH released energy in winds, the momentum feedback model emits more than 30% of the total energy released by the BH in winds. In the momentum feedback model, the degree of fluctuation in both radiant and wind output is considerably larger than in standard treatments. We check that the new model of BH mass accretion agrees with analytic results for the standard Bondi problem.

  16. Using Electronic Drug Monitor Feedback to Improve Adherence to Antiretroviral Therapy Among HIV-Positive Patients in China

    PubMed Central

    DeSilva, Mary Bachman; Hamer, Davidson H.; Xu, Keyi; Zhang, Jianbo; Li, Tao; Wilson, Ira B.; Gill, Christopher J.

    2009-01-01

    Effective antiretroviral therapy (ART) requires excellent adherence. Little is known about how to improve ART adherence in many HIV/AIDS-affected countries, including China. We therefore assessed an adherence intervention among HIV-positive patients in southwestern China. Eighty subjects were enrolled and monitored for 6 months. Sixty-eight remaining subjects were randomized to intervention/control arms. In months 7–12, intervention subjects were counseled using EDM feedback; controls continued with standard of care. Among randomized subjects, mean adherence and CD4 count were 86.8 vs. 83.8% and 297 vs. 357 cells/μl in intervention vs. control subjects, respectively. At month 12, among 64 subjects who completed the trial, mean adherence had risen significantly among intervention subjects to 96.5% but remained unchanged in controls. Mean CD4 count rose by 90 cells/μl and declined by 9 cells/μl among intervention and control subjects, respectively. EDM feedback as a counseling tool appears promising for management of HIV and other chronic diseases. PMID:19771504

  17. Interlocked positive and negative feedback network motifs regulate β-catenin activity in the adherens junction pathway

    PubMed Central

    Klinke, David J.; Horvath, Nicholas; Cuppett, Vanessa; Wu, Yueting; Deng, Wentao; Kanj, Rania

    2015-01-01

    The integrity of epithelial tissue architecture is maintained through adherens junctions that are created through extracellular homotypic protein–protein interactions between cadherin molecules. Cadherins also provide an intracellular scaffold for the formation of a multiprotein complex that contains signaling proteins, including β-catenin. Environmental factors and controlled tissue reorganization disrupt adherens junctions by cleaving the extracellular binding domain and initiating a series of transcriptional events that aim to restore tissue homeostasis. However, it remains unclear how alterations in cell adhesion coordinate transcriptional events, including those mediated by β-catenin in this pathway. Here were used quantitative single-cell and population-level in vitro assays to quantify the endogenous pathway dynamics after the proteolytic disruption of the adherens junctions. Using prior knowledge of isolated elements of the overall network, we interpreted these data using in silico model-based inference to identify the topology of the regulatory network. Collectively the data suggest that the regulatory network contains interlocked network motifs consisting of a positive feedback loop, which is used to restore the integrity of adherens junctions, and a negative feedback loop, which is used to limit β-catenin–induced gene expression. PMID:26224311

  18. Reciprocal Markov Modeling of Feedback Mechanisms Between Emotion and Dietary Choice Using Experience-Sampling Data.

    PubMed

    Lu, Ji; Pan, Junhao; Zhang, Qiang; Dubé, Laurette; Ip, Edward H

    2015-01-01

    With intensively collected longitudinal data, recent advances in the experience-sampling method (ESM) benefit social science empirical research, but also pose important methodological challenges. As traditional statistical models are not generally well equipped to analyze a system of variables that contain feedback loops, this paper proposes the utility of an extended hidden Markov model to model reciprocal the relationship between momentary emotion and eating behavior. This paper revisited an ESM data set (Lu, Huet, & Dube, 2011) that observed 160 participants' food consumption and momentary emotions 6 times per day in 10 days. Focusing on the analyses on feedback loop between mood and meal-healthiness decision, the proposed reciprocal Markov model (RMM) can accommodate both hidden ("general" emotional states: positive vs. negative state) and observed states (meal: healthier, same or less healthy than usual) without presuming independence between observations and smooth trajectories of mood or behavior changes. The results of RMM analyses illustrated the reciprocal chains of meal consumption and mood as well as the effect of contextual factors that moderate the interrelationship between eating and emotion. A simulation experiment that generated data consistent with the empirical study further demonstrated that the procedure is promising in terms of recovering the parameters. PMID:26717120

  19. Reciprocal Markov modeling of feedback mechanisms between emotion and dietary choice using experience sampling data

    PubMed Central

    Lu, Ji; Pan, Junhao; Zhang, Qiang; Dubé, Laurette; Ip, Edward H.

    2015-01-01

    With intensively collected longitudinal data, recent advances in Experience Sampling Method (ESM) benefit social science empirical research, but also pose important methodological challenges. As traditional statistical models are not generally well-equipped to analyze a system of variables that contain feedback loops, this paper proposes the utility of an extended hidden Markov model to model reciprocal relationship between momentary emotion and eating behavior. This paper revisited an ESM data set (Lu, Huet & Dube, 2011) that observed 160 participants’ food consumption and momentary emotions six times per day in 10 days. Focusing on the analyses on feedback loop between mood and meal healthiness decision, the proposed Reciprocal Markov Model (RMM) can accommodate both hidden (“general” emotional states: positive vs. negative state) and observed states (meal: healthier, same or less healthy than usual) without presuming independence between observations and smooth trajectories of mood or behavior changes. The results of RMM analyses illustrated the reciprocal chains of meal consumption and mood as well as the effect of contextual factors that moderate the interrelationship between eating and emotion. A simulation experiment that generated data consistent to the empirical study further demonstrated that the procedure is promising in terms of recovering the parameters. PMID:26717120

  20. Phytoplankton behavior affects ocean mixed layer dynamics through biological-physical feedback mechanisms

    NASA Astrophysics Data System (ADS)

    Sonntag, S.; Hense, I.

    2011-08-01

    Biologically induced changes in physical oceanic properties through phytoplankton provide potential positive and negative feedback loops. In particular, surface floating cyanobacteria, which are expected to be favored from future environmental conditions and can form large surface mats, can increase light absorption and the surface albedo and decrease momentum input from the atmosphere by wind. In this work we study the effect of a changing phytoplankton community composition to one dominated by buoyant cyanobacteria on the physical oceanic properties. We use the water column model General Ocean Turbulence Model and set up an idealized biological model taking into account the phytoplankton species' characteristics as well as the effects of biology on physics. The model results show that an increase of buoyant cyanobacteria leads to substantial changes in the seasonal cycle of the mixed layer. The results furthermore indicate that the effects due to altered absorption and biologically induced reduction of the wind drag are larger than contrary effects due to changes in the surface albedo. Overall, our model results suggest that the development of cyanobacterial surface blooms and their feedbacks on light absorption and wind drag need to be taken into account in ocean models used for climate scenarios in order to capture changes in the dynamics of the upper ocean.

  1. Development of a Video-feedback Intervention to promote Positive Parenting for Children with Autism (VIPP-AUTI).

    PubMed

    Poslawsky, Irina E; Naber, Fabiënne B A; Bakermans-Kranenburg, Marian J; De Jonge, Maretha V; Van Engeland, Herman; Van IJzendoorn, Marinus H

    2014-01-01

    In this paper we describe the development and content of Video-feedback Intervention to promote Positive Parenting for Children with Autism (VIPP-AUTI). VIPP-AUTI is an adapted version of the evidence-based intervention VIPP. The lack of social responsiveness in children with autism often lowers the quality of the parent-child interaction. A wide range of early interventions exist to cope with the disorder. The majority of early interventions for children with autism focus on their deficits of (social) skills, but the number of evidence-based interventions to improve early parent-child interaction patterns is limited. The aim of VIPP-AUTI is to enhance parental sensitivity to children's autistic characteristics, in order to improve child developmental outcome by increased parental support. PMID:24972103

  2. Indirect adaptive output feedback control of a biorobotic AUV using pectoral-like mechanical fins.

    PubMed

    Naik, Mugdha S; Singh, Sahjendra N; Mittal, Rajat

    2009-06-01

    This paper treats the question of servoregulation of autonomous underwater vehicles (AUVs) in the yaw plane using pectoral-like mechanical fins. The fins attached to the vehicle have oscillatory swaying and yawing motion. The bias angle of the angular motion of the fin is used for the purpose of control. Of course, the design approach considered here is applicable to AUVs for other choices of oscillation patterns of the fins, which produce periodic forces and moments. It is assumed that the vehicle parameters, hydrodynamic coefficients, as well the fin forces and moments are unknown. For the trajectory control of the yaw angle, a sampled-data indirect adaptive control system using output (yaw angle) feedback is derived. The control system has a modular structure, which includes a parameter identifier and a stabilizer. For the control law derivation, an internal model of the exosignals (reference signal (constant or ramp) and constant disturbance) is included. Unlike the direct adaptive control scheme, the derived control law is applicable to minimum as well as nonminimum phase biorobotic AUVs (BAUVs). This is important, because for most of the fin locations on the vehicle, the model is a nonminimum phase. In the closed-loop system, the yaw angle trajectory tracking error converges to zero and the remaining state variables remain bounded. Simulation results are presented which show that the derived modular control system accomplishes precise set point yaw angle control and turning maneuvers in spite of the uncertainties in the system parameters using only yaw angle feedback. PMID:19276512

  3. Inhibition of Receptor Dimerization as a Novel Negative Feedback Mechanism of EGFR Signaling

    PubMed Central

    Kluba, Malgorzata; Engelborghs, Yves; Hofkens, Johan; Mizuno, Hideaki

    2015-01-01

    Dimerization of the epidermal growth factor receptor (EGFR) is crucial for initiating signal transduction. We employed raster image correlation spectroscopy to continuously monitor the EGFR monomer-dimer equilibrium in living cells. EGFR dimer formation upon addition of EGF showed oscillatory behavior with a periodicity of about 2.5 min, suggesting the presence of a negative feedback loop to monomerize the receptor. We demonstrated that monomerization of EGFR relies on phospholipase Cγ, protein kinase C, and protein kinase D (PKD), while being independent of Ca2+ signaling and endocytosis. Phosphorylation of the juxtamembrane threonine residues of EGFR (T654/T669) by PKD was identified as the factor that shifts the monomer-dimer equilibrium of ligand bound EGFR towards the monomeric state. The dimerization state of the receptor correlated with the activity of an extracellular signal-regulated kinase, downstream of the EGFR. Based on these observations, we propose a novel, negative feedback mechanism that regulates EGFR signaling via receptor monomerization. PMID:26465157

  4. From quantum mechanics to universal structures of conceptualization and feedback on quantum mechanics

    NASA Astrophysics Data System (ADS)

    Mugur-Schächter, Mioara

    1993-01-01

    In previous works we have established that the spacetime probabilistic organization of the quantum theory is determined by the spacetime characteristics of the operations by which the observer produces the objects to be studied (“states” of microsystems) and obtains qualifications of these. Guided by this first conclusion, we have then built a “general syntax of relativized conceptualization” where any description is explicitly and systematically referred to the two basic epistemic operations by which the conceptor introduces the object to be qualified and then obtains qualifications of it. Inside this syntax there emerges a general typology of the relativized descriptions. Here we show that with respect to this typology the type of the predictive quantum mechanical descriptions acquires a precise definition. It appears that the quantum mechanical formalism has captured and has expressed directly in a mathematical language the most complex form in which can occur a first descriptional phase that lies universally at the bottom of any chain of conceptualization. The main features of the Hilbert-Dirac algorithms are decoded in terms of the general syntax of relativized conceptualization. This renders explicit the semantical contents of the quantum mechanical representations relating each one of these to its mathematical quantum mechanical expression. Basic insufficiencies are thus identified and, correlatively, false problems as well as answers to these, or guides toward answers. Globally the results obtained provide a basis for future attempts at a general mathematical representation of the processes of conceptualization. “Il pourrait, en effet, être dangereux pour l'avenir de la Physique qu'elle se contente trop facilement de purs formalismes, d'images floues et d'explications toutes verbales s'exprimant par des mots à signification imprécise”—Louis de Broglie, Certitudes et Incertitudes de la Science (Albin Michel, Paris, 1965).

  5. A circuit mechanism for differentiating positive and negative associations.

    PubMed

    Namburi, Praneeth; Beyeler, Anna; Yorozu, Suzuko; Calhoon, Gwendolyn G; Halbert, Sarah A; Wichmann, Romy; Holden, Stephanie S; Mertens, Kim L; Anahtar, Melodi; Felix-Ortiz, Ada C; Wickersham, Ian R; Gray, Jesse M; Tye, Kay M

    2015-04-30

    The ability to differentiate stimuli predicting positive or negative outcomes is critical for survival, and perturbations of emotional processing underlie many psychiatric disease states. Synaptic plasticity in the basolateral amygdala complex (BLA) mediates the acquisition of associative memories, both positive and negative. Different populations of BLA neurons may encode fearful or rewarding associations, but the identifying features of these populations and the synaptic mechanisms of differentiating positive and negative emotional valence have remained unknown. Here we show that BLA neurons projecting to the nucleus accumbens (NAc projectors) or the centromedial amygdala (CeM projectors) undergo opposing synaptic changes following fear or reward conditioning. We find that photostimulation of NAc projectors supports positive reinforcement while photostimulation of CeM projectors mediates negative reinforcement. Photoinhibition of CeM projectors impairs fear conditioning and enhances reward conditioning. We characterize these functionally distinct neuronal populations by comparing their electrophysiological, morphological and genetic features. Overall, we provide a mechanistic explanation for the representation of positive and negative associations within the amygdala. PMID:25925480

  6. A Circuit Mechanism for Differentiating Positive and Negative Associations

    PubMed Central

    Namburi, Praneeth; Beyeler, Anna; Yorozu, Suzuko; Calhoon, Gwendolyn G.; Halbert, Sarah A.; Wichmann, Romy; Holden, Stephanie S.; Mertens, Kim L.; Anahtar, Melodi; Felix-Ortiz, Ada C.; Wickersham, Ian R.; Gray, Jesse M.; Tye, Kay M.

    2015-01-01

    The ability to differentiate stimuli predicting positive or negative outcomes is critical for survival, and perturbations of emotional processing underlie many psychiatric disease states. Synaptic plasticity in the basolateral amygdala complex (BLA) mediates the acquisition of associative memories, both positive1,2 and negative3–7. Different populations of BLA neurons may encode fearful or rewarding associations8–10, but the identifying features of these populations and the synaptic mechanisms of differentiating positive and negative emotional valence have remained an enigma. Here, we show that BLA neurons projecting to the nucleus accumbens (NAc projectors) or the centromedial amygdala (CeM projectors) underwent opposing synaptic changes following fear or reward conditioning. We found that photostimulation of NAc projectors supports positive reinforcement while photostimulation of CeM projectors mediates negative reinforcement. Photoinhibition of CeM projectors impaired fear conditioning and enhanced reward conditioning. We then characterized these functionally-distinct neuronal populations by comparing their electrophysiological, morphological and genetic features. We provide a mechanistic explanation for the representation of positive and negative associations within the amygdala. PMID:25925480

  7. Modelling ecogeomorphic feedbacks: investigating mechanisms of land degradation in semi-arid grassland and shrubland

    NASA Astrophysics Data System (ADS)

    Turnbull, Laura; Mueller, Eva; Tietjen, Britta; Wainwright, John

    2014-05-01

    Across vast areas of the world's drylands, land degradation is exacerbated by ecohydrological processes, which alter the structure, function and connectivity of dryland hillslopes. These processes are often interlinked through feedback mechanisms in such a way that a trigger may result in a re-organization of the affected landscape. Here, we present a spatially explicit process-based ecogeomorphic model, MAHLERAN-EcoHyD to enhance our understanding of complex linkages between abiotic and biotic drivers and processes of degradation in drylands. This ecogeomorphic modelling approach is innovative in two main ways: it couples biotic and abiotic processes, and simulates intra and inter-event dynamics, thus overcoming a key limitation of previous modelling approaches in terms of their temporal scaling, by simulating key ecogeomorphic processes at process-relevant time steps. Redistribution of water, sediment and nutrients during high-intensity rainstorms is simulated at 1-sec time steps, soil moisture and transpiration dynamics at daily time steps, and vegetation dynamics (establishment, growth, mortality) at 14-day time steps, over a high-resolution 1x1 m grid. We use this innovative modelling approach to investigate soil-vegetation feedback mechanisms within a grassland-shrubland transition zone at the Sevilleta Long Term Ecological Research site in the south-western United States. Results from three modelling experiments are presented: the first modelling experiment investigates the impact of annual variations in individual high-intensity storms to assess long-term variations in runoff, soil-moisture conditions and sediment and nutrient fluxes over two decades; the second modelling experiment assesses the impact of vegetation composition on spatial changes in surface soil texture due to soil erosion by water; and the third modelling experiment investigates how long-term changes in vegetation alter feedbacks between biotic and abiotic processes using scenarios for

  8. Modal self-excitation by nonlinear acceleration feedback in a class of mechanical systems

    NASA Astrophysics Data System (ADS)

    Malas, Anindya; Chatterjee, S.

    2016-08-01

    The article proposes an acceleration feedback based technique for exciting modal self-oscillation in a class of multi degrees-of-freedom mechanical systems. The controller comprises a bank of second-order filters and the control law is formulated as the nonlinear function of the filter output. A design methodology is developed to excite self-oscillation in any desired mode or combination of modes (mixed-mode oscillation). The choice of control parameters takes into account the control cost and robustness of the controller. The effects of structural damping on the system performance are also studied. Analytical results are confirmed by numerical simulations. An adaptive control is proposed to maintain the oscillation amplitude at the desired level.

  9. Dynamics of mechanical feedback-type hydraulic servomotors under inertia loads

    NASA Technical Reports Server (NTRS)

    Gold, Harold; Otto, Edward W; Ransom, Victor L

    1953-01-01

    An analysis of the dynamics of mechanical feedback-type hydraulic servomotors under inertia loads is developed and experimental verification is presented. The analysis, which is developed in terms of two physical parameters, yields direct expressions for the following dynamic responses: (1) the transient response to a step input and the maximum cylinder pressure during the transient and (2) the variation of amplitude attenuation and phase shift with the frequency of a sinusoidally varying input. The validity of the analysis is demonstrated by means of recorded transient and frequency responses obtained on two servomotors. The calculated responses are in close agreement with the measured responses. The relations presented are readily applicable to the design as well as to the analysis of hydraulic servomotors.

  10. A feedback mechanism converts individual cell features into a supracellular ECM structure in Drosophila trachea

    PubMed Central

    Öztürk-Çolak, Arzu; Moussian, Bernard; Araújo, Sofia J; Casanova, Jordi

    2016-01-01

    The extracellular matrix (ECM), a structure contributed to and commonly shared by many cells in an organism, plays an active role during morphogenesis. Here, we used the Drosophila tracheal system to study the complex relationship between the ECM and epithelial cells during development. We show that there is an active feedback mechanism between the apical ECM (aECM) and the apical F-actin in tracheal cells. Furthermore, we reveal that cell-cell junctions are key players in this aECM patterning and organisation and that individual cells contribute autonomously to their aECM. Strikingly, changes in the aECM influence the levels of phosphorylated Src42A (pSrc) at cell junctions. Therefore, we propose that Src42A phosphorylation levels provide a link for the ECM environment to ensure proper cytoskeletal organisation. DOI: http://dx.doi.org/10.7554/eLife.09373.001 PMID:26836303

  11. Feedback Activation of STAT3 as a Cancer Drug-Resistance Mechanism.

    PubMed

    Zhao, Chengguang; Li, Huameng; Lin, Huey-Jen; Yang, Shulin; Lin, Jiayuh; Liang, Guang

    2016-01-01

    Signal transducer and activator of transcription 3 (STAT3) plays crucial roles in several cellular processes such as cell proliferation and survival, and has been found to be aberrantly activated in many cancers. Much research has explored the leading mechanisms for regulating the STAT3 pathway and its role in promoting tumorigenesis. We focus here on recent evidence suggesting that feedback activation of STAT3 plays a prominent role in mediating drug resistance to a broad spectrum of targeted cancer therapies and chemotherapies. We highlight the potential of co-targeting STAT3 and its primary target to overcome drug resistance, and provide perspective on repurposing clinically approved drugs as STAT3 pathway inhibitors, in combination with the FDA-approved receptor tyrosine kinase (RTK) inhibitors, to improve clinical outcome of cancer treatment. PMID:26576830

  12. Operation of the jet feedback mechanism (JFM) in intermediate luminosity optical transients (ILOTs)

    NASA Astrophysics Data System (ADS)

    Kashi, Amit; Soker, Noam

    2016-06-01

    We follow the premise that most intermediate luminosity optical transients (ILOTs) are powered by rapid mass accretion onto a main sequence star, and study the effects of jets launched by an accretion disk. The disk is formed due to large specific angular momentum of the accreted mass. The two opposite jets might expel some of the mass from the reservoir of gas that feeds the disk, and therefore reduce and shorten the mass accretion process. We argue that by this process ILOTs limit their luminosity and might even shut themselves off in this negative jet feedback mechanism (JFM). The group of ILOTs is a new member of a large family of astrophysical objects whose activity is regulated by the operation of the JFM.

  13. Positive regulation of the Egr-1/osteopontin positive feedback loop in rat vascular smooth muscle cells by TGF-{beta}, ERK, JNK, and p38 MAPK signaling

    SciTech Connect

    Yu, Hong-Wei; Liu, Qi-Feng; Liu, Gui-Nan

    2010-05-28

    Previous studies identified a positive feedback loop in rat vascular smooth muscle cells (VSMCs) in which early growth response factor-1 (Egr-1) binds to the osteopontin (OPN) promoter and upregulates OPN expression, and OPN upregulates Egr-1 expression via the extracellular signal-regulated protein kinase (ERK) signaling pathway. The current study examined whether transforming growth factor-{beta} (TGF-{beta}) activity contributes to Egr-1 binding to the OPN promoter, and whether other signaling pathways act downstream of OPN to regulate Egr-1 expression. ChIP assays using an anti-Egr-1 antibody showed that amplification of the OPN promoter sequence decreased in TGF-{beta} DNA enzyme-transfected VSMCs relative to control VSMCs. Treatment of VSMCs with PD98059 (ERK inhibitor), SP600125 (JNK inhibitor), or SB203580 (p38 MAPK inhibitor) significantly inhibited OPN-induced Egr-1 expression, and PD98059 treatment was associated with the most significant decrease in Egr-1 expression. OPN-stimulated VSMC cell migration was inhibited by SP600125 or SB203580, but not by PD98059. Furthermore, MTT assays showed that OPN-mediated cell proliferation was inhibited by PD98059, but not by SP600125 or SB203580. Taken together, the results of the current study show that Egr-1 binding to the OPN promoter is positively regulated by TGF-{beta}, and that the p38 MAPK, JNK, and ERK pathways are involved in OPN-mediated Egr-1 upregulation.

  14. Hybrid PD and effective multi-mode positive position feedback control for slewing and vibration suppression of a smart flexible manipulator

    NASA Astrophysics Data System (ADS)

    Lou, Jun-qiang; Wei, Yan-ding; Yang, Yi-ling; Xie, Feng-ran

    2015-03-01

    A hybrid control strategy for slewing and vibration suppression of a smart flexible manipulator is presented in this paper. It consists of a proportional derivative controller to realize motion control, and an effective multi-mode positive position feedback (EMPPF) controller to suppress the multi-mode vibration. Rather than treat each mode equally as the standard multi-mode PPF, the essence of the EMPPF is that control forces of different modes are applied according to the mode parameters of the respective modes, so the vibration modes with less vibration energy receive fewer control forces. Stability conditions for the close loop system are established through stability analysis. Optimal parameters of the EMPPF controller are obtained using the method of root locus analysis. The performance of the proposed strategy is demonstrated by simulation and experiments. Experimental results show that the first two vibration modes of the manipulator are effectively suppressed. The setting time of the setup descends approximately 55%, reaching 3.12 s from 5.67 s.

  15. Bisphenol A Induces Fatty Liver by an Endocannabinoid-Mediated Positive Feedback Loop.

    PubMed

    Martella, Andrea; Silvestri, Cristoforo; Maradonna, Francesca; Gioacchini, Giorgia; Allarà, Marco; Radaelli, Giuseppe; Overby, Darryl R; Di Marzo, Vincenzo; Carnevali, Oliana

    2016-05-01

    The xenoestrogen bisphenol A (BPA) is a widespread plasticizer detectable within several ecosystems. BPA is considered a metabolic disruptor, affecting different organs; however, little is known about its mechanism of action in the liver, in which it triggers triglyceride accumulation. Adult zebrafish (Danio rerio) exposed to BPA developed hepatosteatosis, which was associated with an increase in the liver levels of the obesogenic endocannabinoids 2-arachidonoylglycerol and anandamide and a concomitant decrease in palmitoylethanolamide. These changes were associated with variations in the expression of key endocannabinoid catabolic and metabolic enzymes and an increase in the expression of the endocannabinoid receptor cnr1. Acute and chronic in vitro treatments with nano- and micromolar BPA doses showed increased anandamide levels in line with decreased activity of fatty acid amide hydrolase, the main anandamide hydrolytic enzyme, and induced triglyceride accumulation in HHL-5 cells in a CB1-dependent manner. We conclude that BPA is able to produce hepatosteatosis in zebrafish and human hepatocytes by up-regulating the endocannabinoid system. PMID:27014939

  16. Coarse-grained analysis of stochastically simulated cell populations with a positive feedback genetic network architecture.

    PubMed

    Aviziotis, I G; Kavousanakis, M E; Bitsanis, I A; Boudouvis, A G

    2015-06-01

    Among the different computational approaches modelling the dynamics of isogenic cell populations, discrete stochastic models can describe with sufficient accuracy the evolution of small size populations. However, for a systematic and efficient study of their long-time behaviour over a wide range of parameter values, the performance of solely direct temporal simulations requires significantly high computational time. In addition, when the dynamics of the cell populations exhibit non-trivial bistable behaviour, such an analysis becomes a prohibitive task, since a large ensemble of initial states need to be tested for the quest of possibly co-existing steady state solutions. In this work, we study cell populations which carry the lac operon network exhibiting solution multiplicity over a wide range of extracellular conditions (inducer concentration). By adopting ideas from the so-called "equation-free" methodology, we perform systems-level analysis, which includes numerical tasks such as the computation of coarse steady state solutions, coarse bifurcation analysis, as well as coarse stability analysis. Dynamically stable and unstable macroscopic (population level) steady state solutions are computed by means of bifurcation analysis utilising short bursts of fine-scale simulations, and the range of bistability is determined for different sizes of cell populations. The results are compared with the deterministic cell population balance model, which is valid for large populations, and we demonstrate the increased effect of stochasticity in small size populations with asymmetric partitioning mechanisms. PMID:24929336

  17. Pedunculopontine tegmental nucleus lesions impair probabilistic reversal learning by reducing sensitivity to positive reward feedback.

    PubMed

    Syed, Anam; Baker, Phillip M; Ragozzino, Michael E

    2016-05-01

    Recent findings indicate that pedunculopontine tegmental nucleus (PPTg) neurons encode reward-related information that is context-dependent. This information is critical for behavioral flexibility when reward outcomes change signaling a shift in response patterns should occur. The present experiment investigated whether NMDA lesions of the PPTg affects the acquisition and/or reversal learning of a spatial discrimination using probabilistic reinforcement. Male Long-Evans rats received a bilateral infusion of NMDA (30nmoles/side) or saline into the PPTg. Subsequently, rats were tested in a spatial discrimination test using a probabilistic learning procedure. One spatial location was rewarded with an 80% probability and the other spatial location rewarded with a 20% probability. After reaching acquisition criterion of 10 consecutive correct trials, the spatial location - reward contingencies were reversed in the following test session. Bilateral and unilateral PPTg-lesioned rats acquired the spatial discrimination test comparable to that as sham controls. In contrast, bilateral PPTg lesions, but not unilateral PPTg lesions, impaired reversal learning. The reversal learning deficit occurred because of increased regressions to the previously 'correct' spatial location after initially selecting the new, 'correct' choice. PPTg lesions also reduced the frequency of win-stay behavior early in the reversal learning session, but did not modify the frequency of lose-shift behavior during reversal learning. The present results suggest that the PPTg contributes to behavioral flexibility under conditions in which outcomes are uncertain, e.g. probabilistic reinforcement, by facilitating sensitivity to positive reward outcomes that allows the reliable execution of a new choice pattern. PMID:26976089

  18. Neural-mechanical feedback control scheme generates physiological ankle torque fluctuation during quiet stance.

    PubMed

    Vette, Albert H; Masani, Kei; Nakazawa, Kimitaka; Popovic, Milos R

    2010-02-01

    We have recently demonstrated in simulations and experiments that a proportional and derivative (PD) feedback controller can regulate the active ankle torque during quiet stance and stabilize the body despite a long sensory-motor time delay. The purpose of the present study was to: 1) model the active and passive ankle torque mechanisms and identify their contributions to the total ankle torque during standing and 2) investigate whether a neural-mechanical control scheme that implements the PD controller as the neural controller can successfully generate the total ankle torque as observed in healthy individuals during quiet stance. Fourteen young subjects were asked to stand still on a force platform to acquire data for model optimization and validation. During two trials of 30 s each, the fluctuation of the body angle, the electromyogram of the right soleus muscle, and the ankle torque were recorded. Using these data, the parameters of: 1) the active and passive torque mechanisms (Model I) and 2) the PD controller within the neural-mechanical control scheme (Model II) were optimized to achieve potential matching between the measured and predicted ankle torque. The performance of the two models was finally validated with a new set of data. Our results indicate that not only the passive, but also the active ankle torque mechanism contributes significantly to the total ankle torque and, hence, to body stabilization during quiet stance. In addition, we conclude that the proposed neural-mechanical control scheme successfully mimics the physiological control strategy during quiet stance and that a PD controller is a legitimate model for the strategy that the central nervous system applies to regulate the active ankle torque in spite of a long sensory-motor time delay. PMID:20071280

  19. Computational and Experimental Insights into the Mechanism of Substrate Recognition and Feedback Inhibition of Protoporphyrinogen Oxidase

    PubMed Central

    Yang, Sheng-Gang; Wang, Zhi-Fang; Zhan, Chang-Guo; Xi, Zhen; Yang, Guang-Fu

    2013-01-01

    Protoporphyrinogen IX oxidase (PPO; EC 1.3.3.4) is an essential enzyme catalyzing the last common step in the pathway leading to heme and chlorophyll biosynthesis. Great interest in PPO inhibitors arises from both its significance to agriculture and medicine. However, the discovery of PPO inhibitors with ultrahigh potency and selectivity is hampered due to lack of structural and mechanistic understanding about the substrate recognition, which remains a longstanding question central in porphyrin biology. To understand the mechanism, a novel binding model of protogen (protoporphyrinogen IX, the substrate) was developed through extensive computational simulations. Subsequently, amino acid residues that are critical for protogen binding identified by computational simulations were substituted by mutagenesis. Kinetic analyses of these mutants indicated that these residues were critical for protogen binding. In addition, the calculated free energies of protogen binding with these mutants correlated well with the experimental data, indicating the reasonability of the binding model. On the basis of this novel model, the fundamental mechanism of substrate recognition was investigated by performing potential of mean force (PMF) calculations, which provided an atomic level description of conformational changes and pathway intermediates. The free energy profile revealed a feedback inhibition mechanism of proto (protoporphyrin IX, the product), which was also in agreement with experimental evidence. The novel mechanistic insights obtained from this study present a new starting point for future rational design of more efficient PPO inhibitors based on the product-bound PPO structure. PMID:23935953

  20. Autocrine Positive Feedback Regulation of Prolactin Release From Tilapia Prolactin Cells and Its Modulation by Extracellular Osmolality.

    PubMed

    Yamaguchi, Yoko; Moriyama, Shunsuke; Lerner, Darren T; Grau, E Gordon; Seale, Andre P

    2016-09-01

    Prolactin (PRL) is a vertebrate hormone with diverse actions in osmoregulation, metabolism, reproduction, and in growth and development. Osmoregulation is fundamental to maintaining the functional structure of the macromolecules that conduct the business of life. In teleost fish, PRL plays a critical role in osmoregulation in fresh water. Appropriately, PRL cells of the tilapia are directly osmosensitive, with PRL secretion increasing as extracellular osmolality falls. Using a model system that employs dispersed PRL cells from the euryhaline teleost fish, Oreochromis mossambicus, we investigated the autocrine regulation of PRL cell function. Unknown was whether these PRL cells might also be sensitive to autocrine feedback and whether possible autocrine regulation might interact with the well-established regulation by physiologically relevant changes in extracellular osmolality. In the cell-perfusion system, ovine PRL and two isoforms of tilapia PRL (tPRL), tPRL177 and tPRL188, stimulated the release of tPRLs from the dispersed PRL cells. These effects were significant within 5-10 minutes and lasted the entire course of exposure, ceasing within 5-10 minutes of removal of tested PRLs from the perifusion medium. The magnitude of response varied between tPRL177 and tPRL188 and was modulated by extracellular osmolality. On the other hand, the gene expression of tPRLs was mainly unchanged or suppressed by static incubations of PRL cells with added PRLs. By demonstrating the regulatory complexity driven by positive autocrine feedback and its interaction with osmotic stimuli, these findings expand upon the knowledge that pituitary PRL cells are regulated complexly through multiple factors and interactions. PMID:27379370

  1. PYK2 integrates growth factor and cytokine receptors signaling and potentiates breast cancer invasion via a positive feedback loop

    PubMed Central

    Selitrennik, Michael; Lev, Sima

    2015-01-01

    The involvement of ErbB family members in breast cancer progression and metastasis has been demonstrated by many studies. However, the downstream effectors that mediate their migratory and invasive responses have not been fully explored. In this study, we show that the non-receptor tyrosine kinase PYK2 is a key effector of EGFR and HER2 signaling in human breast carcinoma. We found that PYK2 is activated by both EGF and heregulin (HRG) in breast cancer cells, and positively regulates EGF/HRG-induced cell spreading, migration and invasion. PYK2 depletion markedly affects ERK1/2 and STAT3 phosphorylation in response to EGF/HRG as well as to IL8 treatment. Importantly, PYK2 depletion also reduced EGF/HRG-induced MMP9 and IL8 transcription, while IL8 inhibition abrogated EGF-induced MMP9 transcription and attenuated cell invasion. IL8, which is transcriptionally regulated by STAT3 and induces PYK2 activation, prolonged EGF-induced PYK2, STAT3 and ERK1/2 phosphorylation suggesting that IL8 acts through an autocrine loop to reinforce EGF-induced signals. Collectively our studies suggest that PYK2 is a common downstream effector of ErbB and IL8 receptors, and that PYK2 integrates their signaling pathways through a positive feedback loop to potentiate breast cancer invasion. Hence, PYK2 could be a potential therapeutic target for a subset of breast cancer patients. PMID:26084289

  2. Water Vapor Feedback and Links to Mechanisms of Recent Tropical Climate Variations

    NASA Technical Reports Server (NTRS)

    Robertson, F. R.; Miller, Tim L.

    2008-01-01

    Recent variations of tropical climate on interannual to near-decadal scales have provided a useful target for studying feedback processes. A strong warm/cold ENSO couplet (e.g. 1997-2000) along with several subsequent weaker events are prominent interannual signals that are part of an apparent longer term strengthening of the Walker circulation during the mid to late1990 s with some weakening thereafter. Decadal scale changes in tropical SST structure during the 1990s are accompanied by focusing of precipitation over the Indo-Pacific warm pool and an increase in tropical ocean evaporation of order 1.0 %/decade. Here we use a number of diverse satellite measurements to explore connections between upper-tropospheric humidity (UTH) variations on these time scales and changes in other water and energy fluxes. Precipitation (GPCP, TRMM), turbulent fluxes (OAFlux), and radiative fluxes (ERBE / CERES, SRB) are use to analyze vertically-integrated divergence of moist static energy, divMSE, and its dry and moist components. Strong signatures of MSE flux transport linking ascending and descending regions of tropical circulations are found. Relative strengths of these transports compared to radiative flux changes are interpreted as a measure of efficiency in the overall process of heat rejection during episodes of warm or cold SST forcing. In conjunction with the diagnosed energy transports we explore frequency distributions of upper-tropospheric humidity as inferred from SSM/T-2 and AMSU-B passive microwave measurements. Relating these variations to SST changes suggests positive water vapor feedback, but at a level reduced from constant relative humidity.

  3. The positive effect of mirror visual feedback on arm control in children with spastic hemiparetic cerebral palsy is dependent on which arm is viewed.

    PubMed

    Smorenburg, Ana R P; Ledebt, Annick; Feltham, Max G; Deconinck, Frederik J A; Savelsbergh, Geert J P

    2011-09-01

    Mirror visual feedback has previously been found to reduce disproportionate interlimb variability and neuromuscular activity in the arm muscles in children with Spastic Hemiparetic Cerebral Palsy (SHCP). The aim of the current study was to determine whether these positive effects are generated by the mirror per se (i.e. the illusory perception of two symmetrically moving limbs, irrespective of which arm generates the mirror visual feedback) or by the visual illusion that the impaired arm has been substituted and appears to move with less jerk and in synchrony with the less-impaired arm (i.e. by mirror visual feedback of the less-impaired arm only). Therefore, we compared the effect of mirror visual feedback from the impaired and the less-impaired upper limb on the bimanual coupling and neuromuscular activity during a bimanual coordination task. Children with SHCP were asked to perform a bimanual symmetrical circular movement in three different visual feedback conditions (i.e. viewing the two arms, viewing only one arm, and viewing one arm and its mirror image), combined with two head orientation conditions (i.e. looking from the impaired and looking from the less-impaired body side). It was found that mirror visual feedback resulted in a reduction in the eccentric activity of the Biceps Brachii Brevis in the impaired limb compared to the condition with actual visual feedback from the two arms. More specifically, this effect was exclusive to mirror visual feedback from the less-impaired arm and absent when mirror visual feedback from the impaired arm was provided. Across conditions, the less-impaired arm was the leading limb, and the nature of this coupling was independent from visual condition or head orientation. Also, mirror visual feedback did not affect the intensity of the mean neuromuscular activity or the muscle activity of the Triceps Brachii Longus. It was concluded that the positive effects of mirror visual feedback in children with SHCP are not just the

  4. Mechanics of the pulmonary valve in the aortic position.

    PubMed

    Soares, A L F; van Geemen, D; van den Bogaerdt, A J; Oomens, C W J; Bouten, C V C; Baaijens, F P T

    2014-01-01

    Mathematical models can provide valuable information to assess and evaluate the mechanical behavior and remodeling of native tissue. A relevant example when studying collagen remodeling is the Ross procedure because it involves placing the pulmonary autograft in the more demanding aortic valve mechanical environment. The objective of this study was therefore to assess and evaluate the mechanical differences between the aortic valve and pulmonary valve and the remodeling that may occur in the pulmonary valve when placed in the aortic position. The results from biaxial tensile tests of pairs of human aortic and pulmonary valves were compared and used to determine the parameters of a structurally based constitutive model. Finite element analyzes were then performed to simulate the mechanical response of both valves to the aortic diastolic load. Additionally, remodeling laws were applied to assess the remodeling of the pulmonary valve leaflet to the new environment. The pulmonary valve showed to be more extensible and less anisotropic than the aortic valve. When exposed to aortic pressure, the pulmonary leaflet appeared to remodel by increasing its thickness and reorganizing its collagen fibers, rotating them toward the circumferential direction. PMID:24035437

  5. Positive feedback of crop residue incorporation on dissolved organic carbon contents under anaerobic conditions in temperate rice paddy soils

    NASA Astrophysics Data System (ADS)

    Said-Pullicino, Daniel; Sodano, Marcella; Bertora, Chiara; Lerda, Cristina; Sacco, Dario; Celi, Luisella

    2016-04-01

    Rice paddy soils are generally characterized by large concentrations and fluxes of DOC in comparison to other ecosystems. Our recent studies have shown that the combination of relatively high pore-water DOC concentrations under anoxic soil conditions (>10-20 mg C l‑1) and important percolation fluxes of water during field flooding may contribute significant organic C inputs into the subsoil (18-51 g C m‑2) over the cropping season. Crop residues incorporated into the soil after harvest represent the main input of organic C into paddy soils, returning about 200-300 g C m‑2 y‑1 in single-cropped rice paddies. The anaerobic decomposition of these residues may supply important amounts of DOC to soil pore waters. Moreover, the supply of electron donors with the input of residue-derived labile OM may further increase DOC contents by stimulating the microbially-catalyzed reductive dissolution of Fe and Mn oxyhydroxides under anoxic conditions, and release of DOC previously stabilized on the mineral matrix (i.e. positive feedback). This could have important implications on organic C inputs into the subsoil as well as substrate availability for methane production. We therefore hypothesized that crop residue management practices that influence the amount of labile organic matter present in the soil at the time of field flooding may strongly influence soil solution DOC concentrations as well as the positive feedback on the release of soil-derived DOC. We tested this hypothesis at field-scale by evaluating variations in the contents and quality of DOC above and beneath the plough pan over the cropping season as a function of crop residue management practices involving: tillage and crop residue incorporation in spring (SPR), tillage and crop residue incorporation in spring, dry seeding and 1 month delayed flooding (DRY), tillage and crop residue incorporation in autumn (AUT), and straw removal after harvest and tillage in spring (REM). Moreover, we linked changes in DOC

  6. Treatment with recombinant lubricin attenuates osteoarthritis by positive feedback loop between articular cartilage and subchondral bone in ovariectomized rats.

    PubMed

    Cui, Zhuang; Xu, Changpeng; Li, Xue; Song, Jinqi; Yu, Bin

    2015-05-01

    Osteoarthritis (OA) is a most commonly multifactorial degenerative joint disease along with the aging population, particularly in postmenopausal women. During the onset of OA, articular cartilage and subchondral bone act in concert as a functional unit. This present study is to investigate the effects of early or late treatment with recombinant lubricin on the onset of osteoarthritis (OA) in ovariectomized (OVX) rats. We found that both early and late recombinant lubricin treatments attenuated the onset of OA by positive feedback loop between articular cartilage and subchondral bone, although late treatment contributed to a lesser effect compared with early treatment. Specifically, treatment with recombinant lubricin protected articular cartilage from degeneration, demonstrated by lower proteoglycan loss, lower OARSI scores, less calcification cartilage zone and reduced immunostaining for collagen X (Col X) and matrix metalloproteinase (MMP-13) but increased the expression of lubricin, in comparison with vehicle-treated OVX rat group. Further, chondroprotective effects of lubricin normalized bone remodeling in subchondral bone underneath. It's suggested that treatment with recombinant lubricin inhibited the elevation of TRAP and Osterix positive cells in OVX rats and led to the normalization of subchondral bone microarchitectures with the suppression of subsidence of bone volume ratio (BV/TV) and trabecular thickness (Tb.Th) and the increase of trabecular separation (Tb.Sp) in vehicle-treated OVX rats. What's more, the normalization of subchondral bone in turn attenuated the articular cartilage erosion by inhibiting vascular invasion from subchondral bone to calcified cartilage zone, exemplified by inhibiting the elevation of CD31 positive cells in calcified cartilage and angiography in subchondral bone. Together, these results shed light that both early and late recombinant lubricin treatments attenuate the onset of OA by balancing the interplay between articular

  7. Cushing Syndrome Due to ACTH-Secreting Pheochromocytoma, Aggravated by Glucocorticoid-Driven Positive-Feedback Loop

    PubMed Central

    Sakuma, Ikki; Higuchi, Seiichiro; Fujimoto, Masanori; Takiguchi, Tomoko; Nakayama, Akitoshi; Tamura, Ai; Kohno, Takashi; Komai, Eri; Shiga, Akina; Nagano, Hidekazu; Hashimoto, Naoko; Suzuki, Sawako; Mayama, Takafumi; Koide, Hisashi; Ono, Katsuhiko; Sasano, Hironobu; Tatsuno, Ichiro; Yokote, Koutaro

    2016-01-01

    Context: Pheochromocytoma is a catecholamine-producing tumor that originates from adrenal chromaffin cells and is capable of secreting various hormones, including ACTH. Case Description: A 56-year-old female presented with Cushingoid appearance and diabetic ketoacidosis. Endocrinological examinations demonstrated ectopic ACTH production with hypercortisolemia and excess urinary cortisol accompanied by elevated plasma and urine catecholamines. Computed tomography revealed a large left adrenal tumor with bilateral adrenal enlargement. Metaiodobenzylguanidine scintigraphy revealed abnormal accumulation in the tumor, which was eventually diagnosed as pheochromocytoma with ectopic ACTH secretion with subsequent manifestation of Cushing's syndrome. Ectopic ACTH secretion and catecholamine production were blocked by metyrapone treatment, whereas dexamethasone paradoxically increased ACTH secretion. Left adrenalectomy resulted in complete remission of Cushing's syndrome and pheochromocytoma. In Vitro Studies: Immunohistological analysis revealed that the tumor contained two functionally distinct chromaffin-like cell types. The majority of tumor cells stained positive for tyrosine hydroxylase (TH), whereas a minor population of ACTH-positive tumor cells was negative for TH. Furthermore, gene expression and in vitro functional analyses using primary tumor tissue cultures demonstrated that dexamethasone facilitated ACTH as well as catecholamine secretion with parallel induction of proopiomelanocortin (POMC), TH, and phenylethanolamine N-methyltransferase mRNA, supporting a glucocorticoid-dependent positive-feedback loop of ACTH secretion in vivo. DNA methylation analysis revealed that the POMC promoter of this tumor, particularly the E2F binding site, was hypomethylated. Conclusion: We present a case of ectopic ACTH syndrome associated with pheochromocytoma. ACTH up-regulation with paradoxical response to glucocorticoid, possibly through the hypomethylation of the POMC

  8. Individual source positioning mechanism for a nuclear reactor fuel assembly

    SciTech Connect

    Wilson, J.F.; Gjertsen, R.K.; Cerni, S.

    1987-07-07

    A nuclear reactor is described including a fuel assembly, at lest one elongated neutron source rod and an upper core plate. The fuel assembly has top and bottom nozzles with a guide thimbles extending between and interconnecting the nozzles. The upper core plate is positioned adjacent to and above the top nozzle of the fuel assembly and having flow openings to allow passage of coolant from the fuel assembly. At least some of the openings is aligned over respective ones of the guide thimbles with seating means defined about the openings on a lower side of the core plate, a separate mechanism for positioning each individual neutron source rod in a respective guide thimble aligned with one of the openings defined through the upper core plate, comprising: (a) locating means registering against the core plate seating means; and (b) resilient holddown means extending partially into the guide thimble and coupling the source rod with the locating means in a manner which restrains the source rod in a lateral direction and positions the rod in a stationary axial relationship within the guide thimble.

  9. Mechanisms and Feedbacks Causing Changes in Upper Stratospheric Ozone in the 21st Century

    NASA Technical Reports Server (NTRS)

    Oman, Luke; Waugh, D. W.; Kawa, S. R.; Stolarski, R. S.; Douglass, A. R.; Newman, P. A.

    2009-01-01

    Stratospheric ozone is expected to increase during the 21st century as the abundance of halogenated ozone-depleting substances decrease to 1960 values. However, climate change will likely alter this "recovery" of stratospheric ozone by changing stratospheric temperatures, circulation, and abundance of reactive chemical species. Here we quantity the contribution of different mechanisms to changes in upper stratospheric ozone from 1960 to 2100 in the Goddard Earth Observing System Chemistry-Climate Model (GEOS CCM), using multiple linear regression analysis applied to simulations using either Alb or A2 greenhouse gas (GHG) scenarios. In both these scenarios upper stratospheric ozone has a secular increase over the 21st century. For the simulation using the Alb GHG scenario, this increase is determined by the decrease in halogen amounts and the greenhouse gas induced cooling, with roughly equal contributions from each mechanism. There is a larger cooling in the simulation using the A2 GHG scenario, but also enhanced loss from higher NOy and HOx concentrations, which nearly offsets the increase due to cooler temperatures. The resulting ozone evolutions are similar in the A2 and Alb simulations. The response of ozone due to feedbacks from temperature and HOx changes, related to changing halogen concentrations, are also quantified using simulations with fixed halogen concentrations.

  10. [Feedback control mechanisms of plant cell expansion]. Progress report, [June 1989--June 1992

    SciTech Connect

    Cosgrove, D.J.

    1992-12-31

    We have generated considerable evidence for the significance of wall stress relaxation in the control of plant growth and found that several agents (gibberellin, light, genetic loci for dwarf stature) influence growth rate via alteration of wall relaxation. We have refined our methods for measuring wall relaxation and, moreover, have found that wall relaxation properties bear only a distance relationship to wall mechanical properties. We have garnered novel insights into the nature of cell expansion mechanisms by analyzing spontaneous fluctuations of plant growth rate in seedlings. These experiments involved the application of mathematical techniques for analyzing growth rate fluctuations and the development of new instrumentation for measuring and forcing plant growth in a controlled fashion. These studies conclude that growth rate fluctuations generated by the plant as consequence of a feedback control system. This conclusion has important implications for the nature of wall loosening processes and demands a different framework for thinking about growth control. It also implies the existence of a growth rate sensor.

  11. Augmented Feedback Supports Skill Transfer and Reduces High-Risk Injury Landing Mechanics

    PubMed Central

    Myer, Gregory D.; Stroube, Benjamin W.; DiCesare, Christopher A.; Brent, Jensen L.; Ford, Kevin R.; Heidt, Robert S.; Hewett, Timothy E.

    2014-01-01

    feedback on deficits identified by the tuck jump assessment has a positive effect on their biomechanics during a different drop vertical jump task that is related to increased ACL injury risk. The ability of the augmented feedback to support the transfer of skills and injury risk factor reductions across different tasks provides exciting new evidence related to how neuromuscular training may ultimately cross over into retained biomechanics that reduce ACL injuries during sport. Clinical Relevance The tuck jump assessment’s ease of use makes it a timely and economically favorable method to support ACL prevention strategies in young girls. PMID:23371471

  12. Evolution of Double Positive Autoregulatory Feedback Loops in CYCLOIDEA2 Clade Genes Is Associated with the Origin of Floral Zygomorphy[W

    PubMed Central

    Yang, Xia; Pang, Hong-Bo; Liu, Bo-Ling; Qiu, Zhi-Jing; Gao, Qiu; Wei, Lai; Dong, Yang; Wang, Yin-Zheng

    2012-01-01

    Members of the CYCLOIDEA2 (CYC2) clade of the TEOSINTE BRANCHED1, CYCLOIDEA, and PCF transcription factor genes are widely involved in controlling floral zygomorphy, a key innovation in angiosperm evolution, depending on their persistently asymmetric expression in the corresponding floral domains. However, it is unclear how this asymmetric expression is maintained throughout floral development. Selecting Primulina heterotricha as a model, we examined the expression and function of two CYC2 genes, CYC1C and CYC1D. We analyzed the role of their promoters in protein–DNA interactions and transcription activation using electrophoresis mobility shift assays, chromatin immunoprecipitation, and transient gene expression assays. We find that CYC1C and CYC1D positively autoregulate themselves and cross-regulate each other. Our results reveal a double positive autoregulatory feedback loop, evolved for a pair of CYC2 genes to maintain their expression in developing flowers. Further comparative genome analyses, together with the available expression and function data of CYC2 genes in the core eudicots, suggest that this mechanism might have led to the independent origins of floral zygomorphy, which are associated with plant–insect coevolution and the adaptive radiation of angiosperms. PMID:22649271

  13. Reproducibility of The Abdominal and Chest Wall Position by Voluntary Breath-Hold Technique Using a Laser-Based Monitoring and Visual Feedback System

    SciTech Connect

    Nakamura, Katsumasa . E-mail: nakam@radiol.med.kyushu-u.ac.jp; Shioyama, Yoshiyuki; Nomoto, Satoru; Ohga, Saiji; Toba, Takashi; Yoshitake, Tadamasa; Anai, Shigeo; Terashima, Hiromi; Honda, Hiroshi

    2007-05-01

    Purpose: The voluntary breath-hold (BH) technique is a simple method to control the respiration-related motion of a tumor during irradiation. However, the abdominal and chest wall position may not be accurately reproduced using the BH technique. The purpose of this study was to examine whether visual feedback can reduce the fluctuation in wall motion during BH using a new respiratory monitoring device. Methods and Materials: We developed a laser-based BH monitoring and visual feedback system. For this study, five healthy volunteers were enrolled. The volunteers, practicing abdominal breathing, performed shallow end-expiration BH (SEBH), shallow end-inspiration BH (SIBH), and deep end-inspiration BH (DIBH) with or without visual feedback. The abdominal and chest wall positions were measured at 80-ms intervals during BHs. Results: The fluctuation in the chest wall position was smaller than that of the abdominal wall position. The reproducibility of the wall position was improved by visual feedback. With a monitoring device, visual feedback reduced the mean deviation of the abdominal wall from 2.1 {+-} 1.3 mm to 1.5 {+-} 0.5 mm, 2.5 {+-} 1.9 mm to 1.1 {+-} 0.4 mm, and 6.6 {+-} 2.4 mm to 2.6 {+-} 1.4 mm in SEBH, SIBH, and DIBH, respectively. Conclusions: Volunteers can perform the BH maneuver in a highly reproducible fashion when informed about the position of the wall, although in the case of DIBH, the deviation in the wall position remained substantial.

  14. Reward and Visual Feedback Relative to the Performance and Mechanical Efficiency of High School Girls in the Standing Broad Jump.

    ERIC Educational Resources Information Center

    Zebas, Carole J.

    This study focuses on changes occurring in selected mechanical components of high school girls performing the standing broad jump, and collects data pertaining to the effects of monetary reward and videotape feedback upon the following components: (a) distance jumped, (b) maximum angle of knee flexion, (c) maximum angle of hip flexion, (d) hip…

  15. Nongenomic glucocorticoid inhibition via endocannabinoid release in the hypothalamus: a fast feedback mechanism.

    PubMed

    Di, Shi; Malcher-Lopes, Renato; Halmos, Katalin Cs; Tasker, Jeffrey G

    2003-06-15

    Glucocorticoid negative feedback in the brain controls stress, feeding, and neural-immune interactions by regulating the hypothalamic-pituitary-adrenal axis, but the mechanisms of inhibition of hypothalamic neurosecretory cells have never been elucidated. Using whole-cell patch-clamp recordings in an acute hypothalamic slice preparation, we demonstrate a rapid suppression of excitatory glutamatergic synaptic inputs to parvocellular neurosecretory neurons of the hypothalamic paraventricular nucleus (PVN) by the glucocorticoids dexamethasone and corticosterone. The effect was maintained with dexamethasone conjugated to bovine serum albumin and was not seen with direct intracellular glucocorticoid perfusion via the patch pipette, suggesting actions at a membrane receptor. The presynaptic inhibition of glutamate release by glucocorticoids was blocked by postsynaptic inhibition of G-protein activity with intracellular GDP-beta-S application, implicating a postsynaptic G-protein-coupled receptor and the release of a retrograde messenger. The glucocorticoid effect was not blocked by the nitric oxide synthesis antagonist N(G)-nitro-L-arginine methyl ester hydrochloride or by hemoglobin but was blocked completely by the CB1 cannabinoid receptor antagonists AM251 [N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide] and AM281 [1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-4-morpholinyl-1H-pyrazole-3-carboxamide] and mimicked and occluded by the cannabinoid receptor agonist WIN55,212-2 [(beta)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate], indicating that it was mediated by retrograde endocannabinoid release. Several peptidergic subtypes of parvocellular neuron, identified by single-cell reverse transcripton-PCR analysis, were subject to rapid inhibitory glucocorticoid regulation, including corticotropin-releasing hormone-, thyrotropin-releasing hormone

  16. RTVP-1 promotes mesenchymal transformation of glioma via a STAT-3/IL-6-dependent positive feedback loop

    PubMed Central

    Giladi, Nis David; Ziv-Av, Amotz; Lee, Hae Kyung; Finniss, Susan; Cazacu, Simona; Xiang, Cunli; Ben-Asher, Hiba Waldman; deCarvalho, Ana; Mikkelsen, Tom; Poisson, Laila; Brodie, Chaya

    2015-01-01

    Glioblastomas (GBMs), the most aggressive primary brain tumors, exhibit increased invasiveness and resistance to anti-tumor treatments. We explored the role of RTVP-1, a glioma-associated protein that promotes glioma cell migration, in the mesenchymal transformation of GBM. Analysis of The Cancer Genome Atlas (TCGA) demonstrated that RTVP-1 expression was higher in mesenchymal GBM and predicted tumor recurrence and poor clinical outcome. ChiP analysis revealed that the RTVP-1 promoter binds STAT3 and C/EBPβ, two master transcription factors that regulate mesenchymal transformation of GBM. In addition, IL-6 induced RTVP-1 expression in a STAT3-dependent manner. RTVP-1 increased the migration and mesenchymal transformation of glioma cells. Similarly, overexpression of RTVP-1 in human neural stem cells induced mesenchymal differentiation, whereas silencing of RTVP-1 in glioma stem cells (GSCs) decreased the mesenchymal transformation and stemness of these cells. Silencing of RTVP-1 also increased the survival of mice bearing GSC-derived xenografts. Using gene array analysis of RTVP-1 silenced glioma cells we identified IL-6 as a mediator of RTVP-1 effects on the mesenchymal transformation and migration of GSCs, therefore acting in a positive feedback loop by upregulating RTVP-1 expression via the STAT3 pathway. Collectively, these results implicate RTVP-1 as a novel prognostic marker and therapeutic target in GBM. PMID:26267319

  17. Video-feedback Intervention to promote Positive Parenting adapted to Autism (VIPP-AUTI): A randomized controlled trial.

    PubMed

    Poslawsky, Irina E; Naber, Fabiënne Ba; Bakermans-Kranenburg, Marian J; van Daalen, Emma; van Engeland, Herman; van IJzendoorn, Marinus H

    2015-07-01

    In a randomized controlled trial, we evaluated the early intervention program Video-feedback Intervention to promote Positive Parenting adapted to Autism (VIPP-AUTI) with 78 primary caregivers and their child (16-61 months) with Autism Spectrum Disorder. VIPP-AUTI is a brief attachment-based intervention program, focusing on improving parent-child interaction and reducing the child's individual Autism Spectrum Disorder-related symptomatology in five home visits. VIPP-AUTI, as compared with usual care, demonstrated efficacy in reducing parental intrusiveness. Moreover, parents who received VIPP-AUTI showed increased feelings of self-efficacy in child rearing. No significant group differences were found on other aspects of parent-child interaction or on child play behavior. At 3-months follow-up, intervention effects were found on child-initiated joint attention skills, not mediated by intervention effects on parenting. Implementation of VIPP-AUTI in clinical practice is facilitated by the use of a detailed manual and a relatively brief training of interveners. PMID:24919961

  18. Ecological consequences of body size decline in harvested fish species: positive feedback loops in trophic interactions amplify human impact.

    PubMed

    Audzijonyte, Asta; Kuparinen, Anna; Gorton, Rebecca; Fulton, Elizabeth A

    2013-04-23

    Humans are changing marine ecosystems worldwide, both directly through fishing and indirectly through climate change. One of the little explored outcomes of human-induced change involves the decreasing body sizes of fishes. We use a marine ecosystem model to explore how a slow (less than 0.1% per year) decrease in the length of five harvested species could affect species interactions, biomasses and yields. We find that even small decreases in fish sizes are amplified by positive feedback loops in the ecosystem and can lead to major changes in natural mortality. For some species, a total of 4 per cent decrease in length-at-age over 50 years resulted in 50 per cent increase in predation mortality. However, the magnitude and direction in predation mortality changes differed among species and one shrinking species even experienced reduced predation pressure. Nevertheless, 50 years of gradual decrease in body size resulted in 1-35% decrease in biomasses and catches of all shrinking species. Therefore, fisheries management practices that ignore contemporary life-history changes are likely to overestimate long-term yields and can lead to overfishing. PMID:23365151

  19. Positive feedback loop between introductions of non-native marine species and cultivation of oysters in Europe.

    PubMed

    Mineur, Frederic; Le Roux, Auguste; Maggs, Christine A; Verlaque, Marc

    2014-12-01

    With globalization, agriculture and aquaculture activities are increasingly affected by diseases that are spread through movement of crops and stock. Such movements are also associated with the introduction of non-native species via hitchhiking individual organisms. The oyster industry, one of the most important forms of marine aquaculture, embodies these issues. In Europe disease outbreaks affecting cultivated populations of the naturalized oyster Crassostrea gigas caused a major disruption of production in the late 1960s and early 1970s. Mitigation procedures involved massive imports of stock from the species' native range in the northwestern Pacific from 1971 to 1977. We assessed the role stock imports played in the introduction of non-native marine species (including pathogens) from the northwestern Pacific to Europe through a methodological and critical appraisal of record data. The discovery rate of non-native species (a proxy for the introduction rate) from 1966 to 2012 suggests a continuous vector activity over the entire period. Disease outbreaks that have been affecting oyster production since 2008 may be a result of imports from the northwestern Pacific, and such imports are again being considered as an answer to the crisis. Although successful as a remedy in the short and medium terms, such translocations may bring new diseases that may trigger yet more imports (self-reinforcing or positive feedback loop) and lead to the introduction of more hitchhikers. Although there is a legal framework to prevent or reduce these introductions, existing procedures should be improved. PMID:25047099

  20. INSM1 increases N-myc stability and oncogenesis via a positive-feedback loop in neuroblastoma.

    PubMed

    Chen, Chiachen; Breslin, Mary B; Lan, Michael S

    2015-11-01

    Insulinoma associated-1 (IA-1/INSM1) gene is exclusively expressed during early embryonic development, but has been found to be re-expressed at high levels in neuroendocrine tumors including neuroblastoma. Using over-expression and knockdown experiments in neuroblastoma cells, we showed that INSM1 is critical for cell proliferation, BME-coated invasion, and soft agar colony formation. Here, we identified INSM1 as a novel target gene activated by N-myc in N-myc amplified neuroblastoma cells. The Sonic hedgehog signaling pathway induced INSM1 by increasing N-myc expression. INSM1 activated PI3K/AKT/GSK3β pathways to suppress N-myc phosphorylation (Thr-58) and inhibited degradation of N-myc. Inversely, N-myc protein bound to the E2-box region of the INSM1 promoter and activated INSM1 expression. The invasion assay and the xenograft nude mouse tumor model revealed that the INSM1 factor facilitated growth and oncogenesis of neuroblastoma. The current data supports our hypothesis that a positive-feedback loop of sonic hedgehog signaling induced INSM1 through N-myc and INSM1 enhanced N-myc stability contributing to the transformation of human neuroblastoma. PMID:26456864

  1. INSM1 increases N-myc stability and oncogenesis via a positive-feedback loop in neuroblastoma

    PubMed Central

    Chen, Chiachen; Breslin, Mary B.; Lan, Michael S.

    2015-01-01

    Insulinoma associated-1 (IA-1/INSM1) gene is exclusively expressed during early embryonic development, but has been found to be re-expressed at high levels in neuroendocrine tumors including neuroblastoma. Using over-expression and knockdown experiments in neuroblastoma cells, we showed that INSM1 is critical for cell proliferation, BME-coated invasion, and soft agar colony formation. Here, we identified INSM1 as a novel target gene activated by N-myc in N-myc amplified neuroblastoma cells. The Sonic hedgehog signaling pathway induced INSM1 by increasing N-myc expression. INSM1 activated PI3K/AKT/GSK3β pathways to suppress N-myc phosphorylation (Thr-58) and inhibited degradation of N-myc. Inversely, N-myc protein bound to the E2-box region of the INSM1 promoter and activated INSM1 expression. The invasion assay and the xenograft nude mouse tumor model revealed that the INSM1 factor facilitated growth and oncogenesis of neuroblastoma. The current data supports our hypothesis that a positive-feedback loop of sonic hedgehog signaling induced INSM1 through N-myc and INSM1 enhanced N-myc stability contributing to the transformation of human neuroblastoma. PMID:26456864

  2. REDBACK: an Open-Source Highly Scalable Simulation Tool for Rock Mechanics with Dissipative Feedbacks

    NASA Astrophysics Data System (ADS)

    Poulet, T.; Veveakis, M.; Paesold, M.; Regenauer-Lieb, K.

    2014-12-01

    Multiphysics modelling has become an indispensable tool for geoscientists to simulate the complex behaviours observed in their various fields of study where multiple processes are involved, including thermal, hydraulic, mechanical and chemical (THMC) laws. This modelling activity involves simulations that are computationally expensive and its soaring uptake is tightly linked to the increasing availability of supercomputing power and easy access to powerful nonlinear solvers such as PETSc (http://www.mcs.anl.gov/petsc/). The Multiphysics Object-Oriented Simulation Environment (MOOSE) is a finite-element, multiphysics framework (http://mooseframework.org) that can harness such computational power and allow scientists to develop easily some tightly-coupled fully implicit multiphysics simulations that run automatically in parallel on large clusters. This open-source framework provides a powerful tool to collaborate on numerical modelling activities and we are contributing to its development with REDBACK (https://github.com/pou036/redback), a module for Rock mEchanics with Dissipative feedBACKs. REDBACK builds on the tensor mechanics finite strain implementation available in MOOSE to provide a THMC simulator where the energetic formulation highlights the importance of all dissipative terms in the coupled system of equations. We show first applications of fully coupled dehydration reactions triggering episodic fluid transfer through shear zones (Alevizos et al, 2014). The dimensionless approach used allows focusing on the critical underlying variables which are driving the resulting behaviours observed and this tool is specifically designed to study material instabilities underpinning geological features like faulting, folding, boudinage, shearing, fracturing, etc. REDBACK provides a collaborative and educational tool which captures the physical and mathematical understanding of such material instabilities and provides an easy way to apply this knowledge to realistic

  3. A novel Ca2+-feedback mechanism extends the operating range of mammalian rods to brighter light

    PubMed Central

    Turunen, Teemu T.; Heikkinen, Hanna; Pitkänen, Marja

    2015-01-01

    Sensory cells adjust their sensitivity to incoming signals, such as odor or light, in response to changes in background stimulation, thereby extending the range over which they operate. For instance, rod photoreceptors are extremely sensitive in darkness, so that they are able to detect individual photons, but remain responsive to visual stimuli under conditions of bright ambient light, which would be expected to saturate their response given the high gain of the rod transduction cascade in darkness. These photoreceptors regulate their sensitivity to light rapidly and reversibly in response to changes in ambient illumination, thereby avoiding saturation. Calcium ions (Ca2+) play a major role in mediating the rapid, subsecond adaptation to light, and the Ca2+-binding proteins GCAP1 and GCAP2 (or guanylyl cyclase–activating proteins [GCAPs]) have been identified as important mediators of the photoreceptor response to changes in intracellular Ca2+. However, mouse rods lacking both GCAP1 and GCAP2 (GCAP−/−) still show substantial light adaptation. Here, we determined the Ca2+ dependency of this residual light adaptation and, by combining pharmacological, genetic, and electrophysiological tools, showed that an unknown Ca2+-dependent mechanism contributes to light adaptation in GCAP−/− mouse rods. We found that mimicking the light-induced decrease in intracellular [Ca2+] accelerated recovery of the response to visual stimuli and caused a fourfold decrease of sensitivity in GCAP−/− rods. About half of this Ca2+-dependent regulation of sensitivity could be attributed to the recoverin-mediated pathway, whereas half of it was caused by the unknown mechanism. Furthermore, our data demonstrate that the feedback mechanisms regulating the sensitivity of mammalian rods on the second and subsecond time scales are all Ca2+ dependent and that, unlike salamander rods, Ca2+-independent background-induced acceleration of flash response kinetics is rather weak in mouse

  4. Separable Neural Mechanisms Contribute to Feedback Processing in a Rule-Learning Task

    ERIC Educational Resources Information Center

    Zanolie, K.; Van Leijenhorst, L.; Rombouts, S. A. R. B.; Crone, E. A.

    2008-01-01

    To adjust performance appropriately to environmental demands, it is important to monitor ongoing action and process performance feedback for possible errors. In this study, we used fMRI to test whether medial prefrontal cortex (PFC)/anterior cingulate cortex (ACC) and dorsolateral (DL) PFC have different roles in feedback processing. Twenty adults…

  5. Understanding the mechanisms underlying voluntary responses to pitch-shifted auditory feedback

    PubMed Central

    Patel, Sona; Nishimura, Cristina; Lodhavia, Anjli; Korzyukov, Oleg; Parkinson, Amy; Robin, Donald A.; Larson, Charles R.

    2014-01-01

    Previous research has shown that vocal errors can be simulated using a pitch perturbation technique. Two types of responses are observed when subjects are asked to ignore changes in pitch during a steady vowel production, a compensatory response countering the direction of the perceived change in pitch and a following response in the same direction as the pitch perturbation. The present study investigated the nature of these responses by asking subjects to volitionally change their voice fundamental frequency either in the opposite direction (“opposing” group) or the same direction (“following” group) as the pitch shifts (±100 cents, 1000 ms) presented during the speaker's production of an /a/ vowel. Results showed that voluntary responses that followed the stimulus directions had significantly shorter latencies (150 ms) than opposing responses (360 ms). In addition, prior to the slower voluntary opposing responses, there were short latency involuntary responses that followed the stimulus direction. These following responses may involve mechanisms of imitation or vocal shadowing of acoustical stimuli when subjects are predisposed to respond to a change in frequency of a sound. The slower opposing responses may represent a control strategy that requires monitoring and correcting for errors between the feedback signal and the intended vocal goal. PMID:24815283

  6. Model of myosin recruitment to the cell equator for cytokinesis: feedback mechanisms and dynamical regimes

    NASA Astrophysics Data System (ADS)

    Veksler, Alexander; Vavylonis, Dimitrios

    2011-03-01

    The formation and constriction of the contractile ring during cytokinesis, the final step of cell division, depends on the recruitment of motor protein myosin to the cell's equatorial region. During animal cell cytokinesis, cortical myosin filaments (MF) disassemble at the flanking regions and concentrate in the equator. This recruitment depends on myosin motor activity and the Rho proteins that regulate MF assembly and disassembly. Central spindle and astral microtubules help establish a spatial pattern of differential Rho activity. We propose a reaction-diffusion model for the dynamics of MF recruitment to the equatorial region. In the model, the central spindle and mechanical stress promote self-reinforcing MF assembly. Negative feedback is introduced by MF-induced recruitment of inhibitor myosin phosphatase. Our model yields various dynamical regimes and explains both the recruitment of MF to the cleavage furrow and the observed damped MF oscillations in the flanking regions, as well as steady MF assembly. Space and time parameters of MF oscillations are calculated. We predict oscillatory relaxation of cortical MF upon removal of locally-applied external stress.

  7. Explaining the Most Energetic Supernovae with an Inefficient Jet-feedback Mechanism

    NASA Astrophysics Data System (ADS)

    Gilkis, Avishai; Soker, Noam; Papish, Oded

    2016-08-01

    We suggest that the energetic radiation from core-collapse super-energetic supernovae (SESNe) is due to a long-lasting accretion process onto the newly born neutron star (NS), resulting from an inefficient operation of the jet-feedback mechanism (JFM). The jets that are launched by the accreting NS or black hole maintain their axis due to a rapidly rotating pre-collapse core and do not manage to eject core material from near the equatorial plane. The jets are able to eject material from the core along the polar directions and reduce the gravity near the equatorial plane. The equatorial gas expands, and part of it falls back over a timescale of minutes to days to prolong the jet-launching episode. According to the model for SESNe proposed in the present paper, the principal parameter that distinguishes between the different cases of core-collapse supernova (CCSN) explosions, such as between normal CCSNe and SESNe, is the efficiency of the JFM. This efficiency, in turn, depends on the pre-collapse core mass, envelope mass, core convection, and, most of all, the angular momentum profile in the core. One prediction of the inefficient JFM for SESNe is the formation of a slow equatorial outflow in the explosion. The typical velocity and mass of this outflow are estimated to be v eq ≈ 1000 km s‑1 and M eq ≳ 1 M ⊙, respectively, though quantitative values will have to be checked in future hydrodynamic simulations.

  8. Feedback Mechanisms Regulate Ets Variant 2 (Etv2) Gene Expression and Hematoendothelial Lineages.

    PubMed

    Koyano-Nakagawa, Naoko; Shi, Xiaozhong; Rasmussen, Tara L; Das, Satyabrata; Walter, Camille A; Garry, Daniel J

    2015-11-20

    Etv2 is an essential transcriptional regulator of hematoendothelial lineages during embryogenesis. Although Etv2 downstream targets have been identified, little is known regarding the upstream transcriptional regulation of Etv2 gene expression. In this study, we established a novel methodology that utilizes the differentiating ES cell and embryoid body system to define the modules and enhancers embedded within the Etv2 promoter. Using this system, we defined an autoactivating role for Etv2 that is mediated by two adjacent Ets motifs in the proximal promoter. In addition, we defined the role of VEGF/Flk1-Calcineurin-NFAT signaling cascade in the transcriptional regulation of Etv2. Furthermore, we defined an Etv2-Flt1-Flk1 cascade that serves as a negative feedback mechanism to regulate Etv2 gene expression. To complement and extend these studies, we demonstrated that the Flt1 null embryonic phenotype was partially rescued in the Etv2 conditional knockout background. In summary, these studies define upstream and downstream networks that serve as a transcriptional rheostat to regulate Etv2 gene expression. PMID:26396195

  9. Feedback of mechanical effectiveness induces adaptations in motor modules during cycling.

    PubMed

    De Marchis, Cristiano; Schmid, Maurizio; Bibbo, Daniele; Castronovo, Anna Margherita; D'Alessio, Tommaso; Conforto, Silvia

    2013-01-01

    Recent studies have reported evidence that the motor system may rely on a modular organization, even if this behavior has yet to be confirmed during motor adaptation. The aim of the present study is to investigate the modular motor control mechanisms underlying the execution of pedaling by untrained subjects in different biomechanical conditions. We use the muscle synergies framework to characterize the muscle coordination of 11 subjects pedaling under two different conditions. The first one consists of a pedaling exercise with a strategy freely chosen by the subjects (Preferred Pedaling Technique, PPT), while the second condition constrains the gesture by means of a real time visual feedback of mechanical effectiveness (Effective Pedaling Technique, EPT). Pedal forces, recorded using a pair of instrumented pedals, were used to calculate the Index of Effectiveness (IE). EMG signals were recorded from eight muscles of the dominant leg and Non-negative Matrix Factorization (NMF) was applied for the extraction of muscle synergies. All the synergy vectors, extracted cycle by cycle for each subject, were pooled across subjects and conditions and underwent a 2-dimensional Sammon's non-linear mapping. Seven representative clusters were identified on the Sammon's projection, and the corresponding eight-dimensional synergy vectors were used to reconstruct the repertoire of muscle activation for all subjects and all pedaling conditions (VAF > 0.8 for each individual muscle pattern). Only 5 out of the 7 identified modules were used by the subjects during the PPT pedaling condition, while 2 additional modules were found specific for the pedaling condition EPT. The temporal recruitment of three identified modules was highly correlated with IE. The structure of the identified modules was found similar to that extracted in other studies of human walking, partly confirming the existence of shared and task specific muscle synergies, and providing further evidence on the modularity

  10. Feedback of mechanical effectiveness induces adaptations in motor modules during cycling

    PubMed Central

    De Marchis, Cristiano; Schmid, Maurizio; Bibbo, Daniele; Castronovo, Anna Margherita; D'Alessio, Tommaso; Conforto, Silvia

    2013-01-01

    Recent studies have reported evidence that the motor system may rely on a modular organization, even if this behavior has yet to be confirmed during motor adaptation. The aim of the present study is to investigate the modular motor control mechanisms underlying the execution of pedaling by untrained subjects in different biomechanical conditions. We use the muscle synergies framework to characterize the muscle coordination of 11 subjects pedaling under two different conditions. The first one consists of a pedaling exercise with a strategy freely chosen by the subjects (Preferred Pedaling Technique, PPT), while the second condition constrains the gesture by means of a real time visual feedback of mechanical effectiveness (Effective Pedaling Technique, EPT). Pedal forces, recorded using a pair of instrumented pedals, were used to calculate the Index of Effectiveness (IE). EMG signals were recorded from eight muscles of the dominant leg and Non-negative Matrix Factorization (NMF) was applied for the extraction of muscle synergies. All the synergy vectors, extracted cycle by cycle for each subject, were pooled across subjects and conditions and underwent a 2-dimensional Sammon's non-linear mapping. Seven representative clusters were identified on the Sammon's projection, and the corresponding eight-dimensional synergy vectors were used to reconstruct the repertoire of muscle activation for all subjects and all pedaling conditions (VAF > 0.8 for each individual muscle pattern). Only 5 out of the 7 identified modules were used by the subjects during the PPT pedaling condition, while 2 additional modules were found specific for the pedaling condition EPT. The temporal recruitment of three identified modules was highly correlated with IE. The structure of the identified modules was found similar to that extracted in other studies of human walking, partly confirming the existence of shared and task specific muscle synergies, and providing further evidence on the modularity

  11. Feedback based simultaneous correction of imaging artifacts due to geometrical and mechanical cross-talk and tip-sample stick in atomic force microscopy

    NASA Astrophysics Data System (ADS)

    Shegaonkar, Ajit C.; Salapaka, Srinivasa M.

    2007-10-01

    This paper presents a feedback scheme that simultaneously corrects, in real time, for the imaging artifacts caused by cantilever and photosensor misalignments as well as misinterpretations in relative lateral position of the tip with respect to the sample due to the tip-sample stick in atomic force microscopy (AFM). The optical beam bounce method, typically used in AFM for imaging, is sensitive to inaccuracies of cantilever geometry and the relative misalignment of the laser source, cantilever, and the laser sensitive diode from the intended design. These inaccuracies, which contribute to the geometrical cross-talk between the normal and the lateral signals, become prominent at the atomic and subnanometer scales, and thereby impede high resolution imaging studies. The feedback scheme accounts for these artifacts and makes imaging insensitive to, in fact, practically independent of these inaccuracies. This scheme counteracts the lateral twisting dynamics of the cantilever, and as a result, it avoids the misinterpretation problem of the relative lateral position of the cantilever tip from the sample and thereby avoids the corresponding imaging artifacts that are typically prominent in contact mode friction force microscopy (FFM). The feedback scheme consists of simultaneously regulating the normal as well as the lateral cantilever deflection signal at their respective set points. This not only removes the imaging artifacts due to geometrical misalignments, mechanical cross-talk, and irregular sliding but also the corresponding compensatory control signal gives a more accurate real time measure of the lateral interaction force between the sample and the cantilever as compared to the lateral deflection signal used in FFM. Experimental results show significant improvement, and in some cases, practical elimination of the artifacts. The design and implementation of a split piezoassembly needed for the lateral actuation for the feedback scheme are also presented.

  12. Feedback based simultaneous correction of imaging artifacts due to geometrical and mechanical cross-talk and tip-sample stick in atomic force microscopy.

    PubMed

    Shegaonkar, Ajit C; Salapaka, Srinivasa M

    2007-10-01

    This paper presents a feedback scheme that simultaneously corrects, in real time, for the imaging artifacts caused by cantilever and photosensor misalignments as well as misinterpretations in relative lateral position of the tip with respect to the sample due to the tip-sample stick in atomic force microscopy (AFM). The optical beam bounce method, typically used in AFM for imaging, is sensitive to inaccuracies of cantilever geometry and the relative misalignment of the laser source, cantilever, and the laser sensitive diode from the intended design. These inaccuracies, which contribute to the geometrical cross-talk between the normal and the lateral signals, become prominent at the atomic and subnanometer scales, and thereby impede high resolution imaging studies. The feedback scheme accounts for these artifacts and makes imaging insensitive to, in fact, practically independent of these inaccuracies. This scheme counteracts the lateral twisting dynamics of the cantilever, and as a result, it avoids the misinterpretation problem of the relative lateral position of the cantilever tip from the sample and thereby avoids the corresponding imaging artifacts that are typically prominent in contact mode friction force microscopy (FFM). The feedback scheme consists of simultaneously regulating the normal as well as the lateral cantilever deflection signal at their respective set points. This not only removes the imaging artifacts due to geometrical misalignments, mechanical cross-talk, and irregular sliding but also the corresponding compensatory control signal gives a more accurate real time measure of the lateral interaction force between the sample and the cantilever as compared to the lateral deflection signal used in FFM. Experimental results show significant improvement, and in some cases, practical elimination of the artifacts. The design and implementation of a split piezoassembly needed for the lateral actuation for the feedback scheme are also presented. PMID

  13. Mechanisms controlling the SST air-sea heat flux feedback and its dependence on spatial scale

    NASA Astrophysics Data System (ADS)

    Hausmann, Ute; Czaja, Arnaud; Marshall, John

    2016-05-01

    The turbulent air-sea heat flux feedback (α , in {W m}^{-2}{ K}^{-1} ) is a major contributor to setting the damping timescale of sea surface temperature (SST) anomalies. In this study we compare the spatial distribution and magnitude of α in the North Atlantic and the Southern Ocean, as estimated from the ERA-Interim reanalysis dataset. The comparison is rationalized in terms of an upper bound on the heat flux feedback, associated with "fast" atmospheric export of temperature and moisture anomalies away from the marine boundary layer, and a lower bound associated with "slow" export. It is found that regions of cold surface waters (≤ 10° C) are best described as approaching the slow export limit. This conclusion is not only valid at the synoptic scale resolved by the reanalysis data, but also on basin scales. In particular, it applies to the heat flux feedback acting as circumpolar SST anomaly scales are approached in the Southern Ocean, with feedbacks of ≤ 10 {W m}^{-2}{ K}^{-1} . In contrast, the magnitude of the heat flux feedback is close to that expected from the fast export limit over the Gulf Stream and its recirculation with values on the order of ≈40 {W m}^{-2}{ K}^{-1} . Further analysis suggests that this high value reflects a compensation between a moderate thermodynamic adjustment of the boundary layer, which tends to weaken the heat flux feedback, and an enhancement of the surface winds over warm SST anomalies, which tend to enhance the feedback.

  14. Studying citizen science through adaptive management and learning feedbacks as mechanisms for improving conservation.

    PubMed

    Jordan, Rebecca; Gray, Steven; Sorensen, Amanda; Newman, Greg; Mellor, David; Newman, Greg; Hmelo-Silver, Cindy; LaDeau, Shannon; Biehler, Dawn; Crall, Alycia

    2016-06-01

    Citizen science has generated a growing interest among scientists and community groups, and citizen science programs have been created specifically for conservation. We examined collaborative science, a highly interactive form of citizen science, which we developed within a theoretically informed framework. In this essay, we focused on 2 aspects of our framework: social learning and adaptive management. Social learning, in contrast to individual-based learning, stresses collaborative and generative insight making and is well-suited for adaptive management. Adaptive-management integrates feedback loops that are informed by what is learned and is guided by iterative decision making. Participants engaged in citizen science are able to add to what they are learning through primary data collection, which can result in the real-time information that is often necessary for conservation. Our work is particularly timely because research publications consistently report a lack of established frameworks and evaluation plans to address the extent of conservation outcomes in citizen science. To illustrate how our framework supports conservation through citizen science, we examined how 2 programs enacted our collaborative science framework. Further, we inspected preliminary conservation outcomes of our case-study programs. These programs, despite their recent implementation, are demonstrating promise with regard to positive conservation outcomes. To date, they are independently earning funds to support research, earning buy-in from local partners to engage in experimentation, and, in the absence of leading scientists, are collecting data to test ideas. We argue that this success is due to citizen scientists being organized around local issues and engaging in iterative, collaborative, and adaptive learning. PMID:26585836

  15. Dual Positive Feedback Regulation of Protein Degradation of an Extra-cytoplasmic Function σ Factor for Cell Differentiation in Streptomyces coelicolor *

    PubMed Central

    Mao, Xu-Ming; Sun, Ning; Wang, Feng; Luo, Shuai; Zhou, Zhan; Feng, Wei-Hong; Huang, Fang-Liang; Li, Yong-Quan

    2013-01-01

    Here we report that in Streptomyces coelicolor, the protein stability of an ECF σ factor SigT, which is involved in the negative regulation of cell differentiation, was completely dependent on its cognate anti-σ factor RstA. The degradation of RstA caused a ClpP/SsrA-dependent degradation of SigT during cell differentiation. This was consistent with the delayed morphological development or secondary metabolism in the ΔclpP background after rstA deletion or sigT overexpression. Meanwhile, SigT negatively regulated clpP/ssrA expression by directly binding to the clpP promoter (clpPp). The SigT-clpPp interaction could be disrupted by secondary metabolites, giving rise to the stabilized SigT protein and retarded morphological development in a non-antibiotic-producing mutant. Thus a novel regulatory mechanism was revealed that the protein degradation of the ECF σ factor was initiated by the degradation of its anti-σ factor, and was accelerated in a dual positive feedback manner, through regulation by secondary metabolites, to promote rapid and irreversible development of the secondary metabolism. This ingenious cooperation of intracellular components can ensure economical and exquisite control of the ECF σ factor protein level for the proper cell differentiation in Streptomyces. PMID:24014034

  16. Cyclooxygenase-2 in tumor-associated macrophages promotes breast cancer cell survival by triggering a positive-feedback loop between macrophages and cancer cells

    PubMed Central

    Li, Hongzhong; Yang, Bing; Huang, Jing; Lin, Yong; Xiang, Tingxiu; Wan, Jingyuan; Li, Hongyuan; Chouaib, Salem; Ren, Guosheng

    2015-01-01

    Tumor-associated macrophages (TAMs) play an important role in cancer cell survival, however, the mechanism of which remains elusive. In this study, we found that COX-2 was abundantly expressed in breast TAMs, which was correlated to poor prognosis in breast cancer patients. Ectopic over-expression of COX-2 in TAMs enhanced breast cancer cell survival both in vitro and in vivo. COX-2 in TAMs was determined to be essential for the induction and maintenance of M2-phenotype macrophage polarity. COX-2+ TAMs promoted breast cancer cell proliferation and survival by increasing Bcl-2 and P-gp and decreasing Bax in cancer cells. Furthermore, COX-2 in TAMs induced the expression of COX-2 in breast cancer cells, which in turn promoted M2 macrophage polarization. Inhibiting PI3K/Akt pathway in cancer cells suppressed COX-2+ TAMs-induced cancer cell survival. These findings suggest that COX-2, functions as a key cancer promoting factor by triggering a positive-feedback loop between macrophages and cancer cells, which could be exploited for breast cancer prevention and therapy. PMID:26359357

  17. CIZ/NMP4 is expressed in B16 melanoma and forms a positive feedback loop with RANKL to promote migration of the melanoma cells.

    PubMed

    Sakuma, Tomomi; Nakamoto, Tetsuya; Hemmi, Hiroaki; Kitazawa, Sohei; Kitazawa, Riko; Notomi, Takuya; Hayata, Tadayoshi; Ezura, Yoichi; Amagasa, Teruo; Noda, Masaki

    2012-07-01

    Tumor metastasis to bone is a serious pathological situation that causes severe pain, and deterioration in locomoter function. However, the mechanisms underlying tumor metastasis is still incompletely understood. CIZ/NMP4 is a nucleocytoplasmic shuttling protein and its roles in tumor cells have not been known. We, therefore, hypothesized the role of CIZ/NMP4 in B16 melanoma cells that metastasize to bone. CIZ/NMP4 is expressed in B16 cells. The CIZ/NMP4 expression levels are correlated to the metastatic activity in divergent types of melanoma cells. Overexpression of CIZ/NMP4 increased B16 cell migration in Trans-well assay. Conversely, siRNA-based knockdown of CIZ/NMP4 suppressed migratory activity of these cells. As RANKL promotes metastasis of tumor cells in bone, we tested its effect on CIZ in melanoma cells. RANKL treatment enhanced CIZ/NMP4 expression. This increase of CIZ by RANKL promoted migration. Conversely, we identified CIZ/NMP4 binding site in the promoter of RANKL. Furthermore, luciferase assay indicated that CIZ/NMP4 overexpression enhanced RANKL promoter activities, revealing a positive feedback loop of CIZ/NMP4 and RANKL in melanoma. These observations indicate that CIZ/NMP4 is critical regulator of metastasis of melanoma cells. PMID:22307584

  18. FoxM1 promotes breast tumorigenesis by activating PDGF-A and forming a positive feedback loop with the PDGF/AKT signaling pathway.

    PubMed

    Yu, Guanzhen; Zhou, Aidong; Xue, Jianfei; Huang, Chen; Zhang, Xia; Kang, Shin-Hyuk; Chiu, Wen-Tai; Tan, Christina; Xie, Keping; Wang, Jiejun; Huang, Suyun

    2015-05-10

    The autocrine platelet-derived growth factor (PDGF)/PDGF receptor (PDGFR) signaling pathway promotes breast cancer tumorigenesis, but the mechanisms for its dysregulation in breast cancer are largely unknown. In the study, we identified PDGF-A as a novel transcriptional target of FoxM1. FoxM1 directly binds to two sites in the promoter of PDGF-A and activates its transcription. Mutation of these FoxM1-binding sites diminished PDGF-A promoter activity. Increased FoxM1 resulted in the upregulation of PDGF-A, which led to activation of the AKT pathway and increased breast cancer cell proliferation and tumorigenesis, whereas knockdown of FoxM1 does the opposite. Blocking AKT activation with a phosphoinositide 3-kinase/AKT inhibitor decreased FoxM1-induced cell proliferation. Moreover, PDGF/AKT pathway upregulates the expression of FoxM1 in breast cancer cells. Knockdown of PDGF-A or blockade of AKT activation inhibited the expression of FoxM1 in breast cancer cells. Furthermore, expression of FoxM1 significantly correlated with the expression of PDGF-A and the activated AKT signaling pathway in human breast cancer specimens. Our study demonstrates a novel positive regulatory feedback loop between FoxM1 and the PDGF/AKT signaling pathway; this loop contributes to breast cancer cell growth and tumorigenesis. PMID:25869208

  19. A novel hypoxia-induced miR-147a regulates cell proliferation through a positive feedback loop of stabilizing HIF-1α

    PubMed Central

    Wang, Fan; Zhang, Haoxiang; Xu, Naihan; Huang, Nunu; Tian, Caiming; Ye, Anlin; Hu, Guangnan; He, Jie; Zhang, Yaou

    2016-01-01

    ABSTRACT Hypoxia is a general event in solid tumor growth. Therefore, induced cellular responses by hypoxia are important for tumorigenesis and tumor growth. MicroRNAs (miRNAs) have recently emerged as important regulators of hypoxia induced cellular responses. Here we report that miR-147a is a novel and crucial hypoxia induced miRNA. HIF-1α up-regulates the expression of miR-147a, and miR-147a in turn stabilizes and accumulates HIF-1α protein via directly targeting HIF-3α, a dominant negative regulator of HIF-1α. Subsequent studies in xenograft mouse model reveal that miR-147a is capable of inhibiting tumor growth. Collectively, these data demonstrate a positive feedback loop between HIF-1α, miR-147a and HIF-3α, which provide a new insight into the mechanism of miR-147a induced cell proliferation arrest under hypoxia. PMID:27260617

  20. Endothelin signaling activates Mef2c expression in the neural crest through a MEF2C-dependent positive-feedback transcriptional pathway.

    PubMed

    Hu, Jianxin; Verzi, Michael P; Robinson, Ashley S; Tang, Paul Ling-Fung; Hua, Lisa L; Xu, Shan-Mei; Kwok, Pui-Yan; Black, Brian L

    2015-08-15

    Endothelin signaling is essential for neural crest development, and dysregulated Endothelin signaling is associated with several neural crest-related disorders, including Waardenburg and other syndromes. However, despite the crucial roles of this pathway in neural crest development and disease, the transcriptional effectors directly activated by Endothelin signaling during neural crest development remain incompletely elucidated. Here, we establish that the MADS box transcription factor MEF2C is an immediate downstream transcriptional target and effector of Endothelin signaling in the neural crest. We show that Endothelin signaling activates Mef2c expression in the neural crest through a conserved enhancer in the Mef2c locus and that CRISPR-mediated deletion of this Mef2c neural crest enhancer from the mouse genome abolishes Endothelin induction of Mef2c expression. Moreover, we demonstrate that Endothelin signaling activates neural crest expression of Mef2c by de-repressing MEF2C activity through a Calmodulin-CamKII-histone deacetylase signaling cascade. Thus, these findings identify a MEF2C-dependent, positive-feedback mechanism for Endothelin induction and establish MEF2C as an immediate transcriptional effector and target of Endothelin signaling in the neural crest. PMID:26160899

  1. The role of feedback mechanisms in the initial development of the constructed catchment Chicken Creek

    NASA Astrophysics Data System (ADS)

    Schaaf, Wolfgang; Hinz, Christoph; Gerwin, Werner; Zaplata, Markus; Hüttl, Reinhard F.

    2015-04-01

    Over a period of ten years, we investigated the initial development of the constructed catchment 'Chicken Creek', south of Cottbus, Germany (Gerwin et al., 2009). Since the boundary conditions and inner structures of the hillslope are well known and documented (Gerwin et al., 2011), the site offers unique possibilities to study the relevant processes of ecosystem development interacting with various structures and patterns. We observed considerable changes within the catchment (Elmer et al., 2013). Both internal and external factors could be identified as driving forces for the formation of structures and patterns in the artificial catchment. Initial structures formed by the construction process and initial substrate characteristics were decisive for the distribution and flow of water. External factors like episodic events triggered erosion and dissection during this initial phase, promoted by the low vegetation cover and the unconsolidated sandy substrate (Schaaf et al., 2013). With time, secondary structures and patterns evolved and became more and more important. Invading biota and vegetation succession initialized abiotic/biotic feedback mechanisms resulting in pattern and habitat formation, and generally in increased differentiation, heterogeneity and complexity that are typical characteristics of ecosystems (Schaaf et al., 2011). The processes and feedback mechanisms in the initial development of a new landscape may deviate in rates, intensity, and dominance from those known from mature ecosystems. It is therefore crucial to understand these early phases of ecosystem development and to disentangle the increasingly complex interactions between the evolving terrestrial and aquatic, biotic, and abiotic compartments of the system. Elmer M, Gerwin W, Schaaf W, Zaplata MK, Hohberg K, Nenov R, Bens O, Hüttl RF (2013): Dynamics of initial ecosystem development at the artificial catchment Chicken Creek, Lusatia, Germany. Environ Earth Sci 69, 491-505. Gerwin W

  2. The role of feedback mechanisms in historic channel changes of the lower Rio Grande in the Big Bend region

    NASA Astrophysics Data System (ADS)

    Dean, David J.; Schmidt, John C.

    2011-03-01

    Over the last century, large-scale water development of the upper Rio Grande in the U.S. and Mexico, and of the Rio Conchos in Mexico, has resulted in progressive channel narrowing of the lower Rio Grande in the Big Bend region. We used methods operating at multiple spatial and temporal scales to analyze the rate, magnitude, and processes responsible for channel narrowing. These methods included: hydrologic analysis of historic stream gage data, analysis of notes of measured discharges, historic oblique and aerial photograph analysis, and stratigraphic and dendrogeomorphic analysis of inset floodplain deposits. Our analyses indicate that frequent large floods between 1900 and the mid-1940s acted as a negative feedback mechanism and maintained a wide, sandy, multi-threaded river. Declines in mean and peak flow in the mid-1940s resulted in progressive channel narrowing. Channel narrowing has been temporarily interrupted by occasional large floods that widened the channel, however, channel narrowing has always resumed. After large floods in 1990 and 1991, the active channel width of the lower Rio Grande has narrowed by 36-52%. Narrowing has occurred by the vertical accretion of fine-grained deposits on top of sand and gravel bars, inset within natural levees. Channel narrowing by vertical accretion occurred simultaneously with a rapid invasion of non-native riparian vegetation ( Tamarix spp., Arundo donax) which created a positive feedback and exacerbated the processes of channel narrowing and vertical accretion. In two floodplain trenches, we measured 2.75 and 3.5 m of vertical accretion between 1993 and 2008. In some localities, nearly 90% of bare, active channel bars were converted to vegetated floodplain during the same period. Upward shifts of stage-discharge relations occurred resulting in over-bank flooding at lower discharges, and continued vertical accretion despite a progressive reduction in stream flow. Thus, although the magnitude of the average annual

  3. Music as a feedback mechanism for teaching head control to severely handicapped children: a pilot study.

    PubMed

    Walmsley, R P; Crichton, L; Droog, D

    1981-12-01

    Five profoundly mentally retarded cerebral-palsied children were studied in order to determine the effectiveness of music as a biofeedback mechanism in the training of head control. The method used a Head Position Trainer and Time Event Counter, developed at the Ontario Crippled Children's Centre in Toronto. Improvement was obtained in three of the five children in their ability to control their head movements when music was used as the biofeedback stimulus. However, these results should be treated cautiously because the sample was small and the training period was brief. PMID:7319141

  4. The cotton MYB108 forms a positive feedback regulation loop with CML11 and participates in the defense response against Verticillium dahliae infection

    PubMed Central

    Cheng, Huan-Qing; Han, Li-Bo; Yang, Chun-Lin; Wu, Xiao-Min; Zhong, Nai-Qin; Wu, Jia-He; Wang, Fu-Xin; Xia, Gui-Xian

    2016-01-01

    Accumulating evidence indicates that plant MYB transcription factors participate in defense against pathogen attack, but their regulatory targets and related signaling processes remain largely unknown. Here, we identified a defense-related MYB gene (GhMYB108) from upland cotton (Gossypium hirsutum) and characterized its functional mechanism. Expression of GhMYB108 in cotton plants was induced by Verticillium dahliae infection and responded to the application of defense signaling molecules, including salicylic acid, jasmonic acid, and ethylene. Knockdown of GhMYB108 expression led to increased susceptibility of cotton plants to V. dahliae, while ecotopic overexpression of GhMYB108 in Arabidopsis thaliana conferred enhanced tolerance to the pathogen. Further analysis demonstrated that GhMYB108 interacted with the calmodulin-like protein GhCML11, and the two proteins form a positive feedback loop to enhance the transcription of GhCML11 in a calcium-dependent manner. Verticillium dahliae infection stimulated Ca2+ influx into the cytosol in cotton root cells, but this response was disrupted in both GhCML11-silenced plants and GhMYB108-silenced plants in which expression of several calcium signaling-related genes was down-regulated. Taken together, these results indicate that GhMYB108 acts as a positive regulator in defense against V. dahliae infection by interacting with GhCML11. Furthermore, the data also revealed the important roles and synergetic regulation of MYB transcription factor, Ca2+, and calmodulin in plant immune responses. PMID:26873979

  5. The cotton MYB108 forms a positive feedback regulation loop with CML11 and participates in the defense response against Verticillium dahliae infection.

    PubMed

    Cheng, Huan-Qing; Han, Li-Bo; Yang, Chun-Lin; Wu, Xiao-Min; Zhong, Nai-Qin; Wu, Jia-He; Wang, Fu-Xin; Wang, Hai-Yun; Xia, Gui-Xian

    2016-04-01

    Accumulating evidence indicates that plant MYB transcription factors participate in defense against pathogen attack, but their regulatory targets and related signaling processes remain largely unknown. Here, we identified a defense-related MYB gene (GhMYB108) from upland cotton (Gossypium hirsutum) and characterized its functional mechanism. Expression of GhMYB108 in cotton plants was induced by Verticillium dahliae infection and responded to the application of defense signaling molecules, including salicylic acid, jasmonic acid, and ethylene. Knockdown of GhMYB108 expression led to increased susceptibility of cotton plants to V. dahliae, while ecotopic overexpression of GhMYB108 in Arabidopsis thaliana conferred enhanced tolerance to the pathogen. Further analysis demonstrated that GhMYB108 interacted with the calmodulin-like protein GhCML11, and the two proteins form a positive feedback loop to enhance the transcription of GhCML11 in a calcium-dependent manner. Verticillium dahliae infection stimulated Ca(2+) influx into the cytosol in cotton root cells, but this response was disrupted in both GhCML11-silenced plants and GhMYB108-silenced plants in which expression of several calcium signaling-related genes was down-regulated. Taken together, these results indicate that GhMYB108 acts as a positive regulator in defense against V. dahliae infection by interacting with GhCML11. Furthermore, the data also revealed the important roles and synergetic regulation of MYB transcription factor, Ca(2+), and calmodulin in plant immune responses. PMID:26873979

  6. Immediate effect of visual and auditory feedback to control the running mechanics of well-trained athletes.

    PubMed

    Eriksson, Martin; Halvorsen, Kjartan A; Gullstrand, Lennart

    2011-02-01

    The correlation between mechanical factors of running and running economy as measured by metabolic cost is a subject of much interest in the study of locomotion. However, no change in running technique has been shown to result in an immediate improvement in running economy on an intra-individual basis. To evaluate the effect of a modified running technique, it is probably necessary that the individual trains with the new technique for a longer period using a feedback system to control the new kinematics. In this study, we examine the feasibility of using visual and auditory feedback to adapt running technique according to a simplistic model of the mechanical cost of running. The model considers only the mechanical work against gravity, which is the product of the magnitude of the vertical displacement of the runner's centre of mass and the step-frequency. In the experiments reported here, 18 trained runners, running at 16 km · h(-1) on a treadmill, were given feedback on these parameters together with indicated target levels. In almost all cases, the runners were able to adjust their technique accordingly. PMID:21170792

  7. Neural mechanism of oculomotor horizontal velocity-to- position temporal integration

    NASA Astrophysics Data System (ADS)

    Aksay, Emre R. F.

    Storage of briefly presented information in ``working'' memory correlates with persistent firing in the brain. Persistent activity in response to transient stimulation is a form of neural temporal integration. Here, the mechanism of temporal integration was explored in the oculomotor velocity-to-position neural integrator (VPNI), where persistent activity is used to maintain eye position and fixation. Extracellular and intracellular electrophysiology, single-cell dye- labeling, and pharmacological inactivation were performed in awake behaving goldfish while monitoring eye motion with the scleral search-coil method. Neurons identified within a compact subnucleus in the medulla designated as Area I are part of the VPNI for horizontal eye movements. Neurons fired tonically during fixations, with tonic rate higher for lateral eye positions and no discharge below a threshold position value. Dye-labeled somata were localized in a 350 micron extent of the inferior reticular formation. Axons either projected ipsilaterally to abducens motoneurons, or crossed the midline and projected toward the contralateral Area I and abducens. Bilateral inactivation of Area I induced inability to maintain eccentric gaze. During intracellular recording, step changes in eye position and firing rate were accompanied by steps in underlying membrane potential. Steps remained when neurons were hyperpolarized below action potential threshold. Perturbation with brief intracellular current pulses only induced transient changes in firing rate and potential. Membrane potential fluctuations were greater during more depolarized steps. These results suggest that steps are generated by synaptic input changes rather than intrinsic properties like membrane multistability. Spiking of unilateral pairs was positively correlated with 0-10 ms lag. Bilateral pairs were negatively correlated with 0-10 ms lag. These results are consistent with excitatory connections between unilateral pairs and inhibitory

  8. Caging Mechanism for a drag-free satellite position sensor

    NASA Technical Reports Server (NTRS)

    Hacker, R.; Mathiesen, J.; Debra, D. B.

    1976-01-01

    A disturbance compensation system for satellites based on the drag-free concept was mechanized and flown, using a spherical proof mass and a cam-guided caging mechanism. The caging mechanism controls the location of the proof mass for testing and constrains it during launch. Design requirements, design details, and hardware are described.

  9. Positive or negative? The impact of X-ray feedback on the formation of direct collapse black hole seeds

    NASA Astrophysics Data System (ADS)

    Regan, John A.; Johansson, Peter H.; Wise, John H.

    2016-09-01

    A nearby source of Lyman-Werner (LW) photons is thought to be a central component in dissociating H2 and allowing for the formation of a direct collapse black hole seed. Nearby sources are also expected to produce copious amounts of hydrogen ionizing photons and X-ray photons. We study here the feedback effects of the X-ray photons by including a spectrum due to high-mass X-ray binaries on top of a galaxy with a stellar spectrum. We explicitly trace photon packages emerging from the nearby source and track the radiative and chemical effects of the multifrequency source (Ephoton = 0.76 eV → 7500 eV). We find that X-rays have a strongly negative feedback effect, compared to a stellar only source, when the radiative source is placed at a separation greater than ≳ 1 kpc. The X-rays heat the low and medium density gas in the envelope surrounding the collapsing halo suppressing the mass inflow. The result is a smaller enclosed mass compared to the stellar only case. However, for separations of ≲ 1 kpc, the feedback effects of the X-rays becomes somewhat neutral. The enhanced LW intensity at close separations dissociates more H2 and this gas is heated due to stellar photons alone, the addition of X-rays is then not significant. This distance dependence of X-ray feedback suggests that a Goldilocks zone exists close to a forming galaxy where X-ray photons have a much smaller negative feedback effect and ideal conditions exist for creating massive black hole seeds.

  10. Developing an Undergraduate Assessment Test: A Mechanism for Faculty Feedback about Retention

    ERIC Educational Resources Information Center

    Callahan, Thomas J.; Strandholm, Karen; Dziekan, Julie

    2010-01-01

    A regional business school chose to self develop an assessment test of the fundamental concepts of the undergraduate business core. Above and beyond the demands of AACSB accreditation, faculty identified feedback from such a test as an essential precursor to changing both overall curriculum and individual class content. The authors describe the…

  11. Carriage-rail assembly for high-resolution mechanical positioning

    NASA Technical Reports Server (NTRS)

    Bosworth, R. H.; Roney, B. W.

    1970-01-01

    Carriage-rail assembly effects extreme resolution and position accuracy with little friction, and is applicable to such apparatus as optical benches, inspection fixtures, machine tools, and photographic equipment. Directions for assembly construction are given.

  12. Stochasticity and bifurcations in a reduced model with interlinked positive and negative feedback loops of CREB1 and CREB2 stimulated by 5-HT.

    PubMed

    Hao, Lijie; Yang, Zhuoqin; Bi, Yuanhong

    2016-04-01

    The cyclic AMP (cAMP)-response element-binding protein (CREB) family of transcription factors is crucial in regulating gene expression required for long-term memory (LTM) formation. Upon exposure of sensory neurons to the neurotransmitter serotonin (5-HT), CREB1 is activated via activation of the protein kinase A (PKA) intracellular signaling pathways, and CREB2 as a transcriptional repressor is relieved possibly via phosphorylation of CREB2 by mitogen-activated protein kinase (MAPK). Song et al. [18] proposed a minimal model with only interlinked positive and negative feedback loops of transcriptional regulation by the activator CREB1 and the repressor CREB2. Without considering feedbacks between the CREB proteins, Pettigrew et al. [8] developed a computational model characterizing complex dynamics of biochemical pathways downstream of 5-HT receptors. In this work, to describe more simply the biochemical pathways and gene regulation underlying 5-HT-induced LTM, we add the important extracellular sensitizing stimulus 5-HT as well as the product Ap-uch into the Song's minimal model. We also strive to examine dynamical properties of the gene regulatory network under the changing concentration of the stimulus, [5-HT], cooperating with the varying positive feedback strength in inducing a high state of CREB1 for the establishment of long-term memory. Different dynamics including monostability, bistability and multistability due to coexistence of stable steady states and oscillations is investigated by means of codimension-2 bifurcation analysis. At the different positive feedback strengths, comparative analysis of deterministic and stochastic dynamics reveals that codimension-1 bifurcation with respect to [5-HT] as the parameter can predict diverse stochastic behaviors resulted from the finite number of molecules, and the number of CREB1 molecules more and more preferentially resides near the high steady state with increasing [5-HT], which contributes to long

  13. HGF/Met and FOXM1 Form a Positive Feedback Loop and Render Pancreatic Cancer Cells Resistance to Met Inhibition and Aggressive Phenotypes

    PubMed Central

    Cui, Jiujie; Xia, Tian; Xie, Dacheng; Gao, Yong; Jia, Zhiliang; Wei, Daoyan; Wang, Liang; Huang, Suyun; Quan, Ming; Xie, Keping

    2015-01-01

    Purpose Hepatocyte growth factor (HGF)/Met signaling plays critical roles in pancreatic ductal adenocarcinoma (PDA) development and progression and is considered a potential therapeutic target for this disease. However, the mechanism of aberrant activation of HGF/Met signaling and resistance to Met inhibition in PDA remains unclear. Experimental Design The mechanistic role of cross-talk between Forkhead box M1 (FOXM1) and HGF/Met signaling in promotion of PDA growth and resistance to Met inhibition was examined using cell culture, molecular biology and mouse models; and the relevance of our experimental and mechanistic findings were validated using human PDA tissues. Results Met was markedly overexpressed in both PDA cell lines and pancreatic tumor specimens, and the expression of Met correlated directly with that of FOXM1 in human tumor specimens. Mechanistically, FOXM1 bound to the promoter region of the Met gene and transcriptionally increased the expression of Met. Increased expression of FOXM1 enhanced the activation of HGF/Met signaling and its downstream pathways, including RAS/extracellular signal-regulated kinase 1/2, phosphoinositide 3-kinase/AKT, and signal transducer and activator of transcription 3. Furthermore, activation of HGF/Met signaling increased the expression and transcriptional activity of FOXM1, and the cross-talk between FOXM1 and HGF/Met signaling promoted PDA growth and resistance to Met inhibition. Conclusions Collectively, our findings identified a positive feedback loop formed by FOXM1 and HGF/Met and revealed that this loop is a potentially effective therapeutic target for PDA. PMID:26876216

  14. Downregulation of COMMD1 by miR-205 promotes a positive feedback loop for amplifying inflammatory- and stemness-associated properties of cancer cells

    PubMed Central

    Yeh, D-W; Chen, Y-S; Lai, C-Y; Liu, Y-L; Lu, C-H; Lo, J-F; Chen, L; Hsu, L-C; Luo, Y; Xiang, R; Chuang, T-H

    2016-01-01

    Sustained activation of nuclear factor-κB (NF-κB) in cancer cells has been shown to promote inflammation, expansion of cancer stem cell (CSC) population, and tumor development. In contrast, recent studies reveal that CSCs exhibit increased inflammation due to constitutive NF-κB activation; however, the underlying molecular mechanism remains unclear. In the present study, the analysis of microarray data revealed upregulation of NF-κB-regulated pro-inflammatory genes and downregulation of copper metabolism MURR1 domain-containing 1 (COMMD1) during the enrichment for stemness in SAS head and neck squamous-cell carcinoma (HNSCC) cells. The 3′-UTR of COMMD1 mRNA contains microRNA (miR)-205 target site. Parallel studies with HNSCC and NSCLC cells indicated that miR-205 is upregulated upon NF-κB activation and suppresses COMMD1 expression in stemness-enriched cancer cells. COMMD1 negatively regulates the inflammatory responses induced by TLR agonists, IL-1β, and TNF-α by targeting RelA for degradation. The shRNA-mediated downregulation of COMMD1 in cancer cells enhanced inflammatory response, generating favorable conditions for macrophage recruitment. In addition, genes associated with stemness were also upregulated in these cells, which exhibited increased potential for anchorage-independent growth. Furthermore, COMMD1 downregulation promoted in vivo tumorigenesis and tumor growth, and tumors derived from COMMD1-knockdown cells displayed elevated level of NF-κB activation, increased expression of inflammatory- and stemness-associated genes, and contain expanded population of tumor-associated leukocytes and stemness-enriched cancer cells. These results suggest that COMMD1 downregulation by miR-205 promotes tumor development by modulating a positive feedback loop that amplifies inflammatory- and stemness-associated properties of cancer cells. PMID:26586569

  15. Downregulation of COMMD1 by miR-205 promotes a positive feedback loop for amplifying inflammatory- and stemness-associated properties of cancer cells.

    PubMed

    Yeh, D-W; Chen, Y-S; Lai, C-Y; Liu, Y-L; Lu, C-H; Lo, J-F; Chen, L; Hsu, L-C; Luo, Y; Xiang, R; Chuang, T-H

    2016-05-01

    Sustained activation of nuclear factor-κB (NF-κB) in cancer cells has been shown to promote inflammation, expansion of cancer stem cell (CSC) population, and tumor development. In contrast, recent studies reveal that CSCs exhibit increased inflammation due to constitutive NF-κB activation; however, the underlying molecular mechanism remains unclear. In the present study, the analysis of microarray data revealed upregulation of NF-κB-regulated pro-inflammatory genes and downregulation of copper metabolism MURR1 domain-containing 1 (COMMD1) during the enrichment for stemness in SAS head and neck squamous-cell carcinoma (HNSCC) cells. The 3'-UTR of COMMD1 mRNA contains microRNA (miR)-205 target site. Parallel studies with HNSCC and NSCLC cells indicated that miR-205 is upregulated upon NF-κB activation and suppresses COMMD1 expression in stemness-enriched cancer cells. COMMD1 negatively regulates the inflammatory responses induced by TLR agonists, IL-1β, and TNF-α by targeting RelA for degradation. The shRNA-mediated downregulation of COMMD1 in cancer cells enhanced inflammatory response, generating favorable conditions for macrophage recruitment. In addition, genes associated with stemness were also upregulated in these cells, which exhibited increased potential for anchorage-independent growth. Furthermore, COMMD1 downregulation promoted in vivo tumorigenesis and tumor growth, and tumors derived from COMMD1-knockdown cells displayed elevated level of NF-κB activation, increased expression of inflammatory- and stemness-associated genes, and contain expanded population of tumor-associated leukocytes and stemness-enriched cancer cells. These results suggest that COMMD1 downregulation by miR-205 promotes tumor development by modulating a positive feedback loop that amplifies inflammatory- and stemness-associated properties of cancer cells. PMID:26586569

  16. Modeling the relativistic runaway electron avalanche and the feedback mechanism with GEANT4

    NASA Astrophysics Data System (ADS)

    Skeltved, Alexander Broberg; Østgaard, Nikolai; Carlson, Brant; Gjesteland, Thomas; Celestin, Sebastien

    2014-11-01

    This paper presents the first study that uses the GEometry ANd Tracking 4 (GEANT4) toolkit to do quantitative comparisons with other modeling results related to the production of terrestrial gamma ray flashes and high-energy particle emission from thunderstorms. We will study the relativistic runaway electron avalanche (RREA) and the relativistic feedback process, as well as the production of bremsstrahlung photons from runaway electrons. The Monte Carlo simulations take into account the effects of electron ionization, electron by electron (Møller), and electron by positron (Bhabha) scattering as well as the bremsstrahlung process and pair production, in the 250 eV to 100 GeV energy range. Our results indicate that the multiplication of electrons during the development of RREAs and under the influence of feedback are consistent with previous estimates. This is important to validate GEANT4 as a tool to model RREAs and feedback in homogeneous electric fields. We also determine the ratio of bremsstrahlung photons to energetic electrons Nγ/Ne. We then show that the ratio has a dependence on the electric field, which can be expressed by the avalanche time τ(E) and the bremsstrahlung coefficient α(ɛ). In addition, we present comparisons of GEANT4 simulations performed with a "standard" and a "low-energy" physics list both validated in the 1 keV to 100 GeV energy range. This comparison shows that the choice of physics list used in GEANT4 simulations has a significant effect on the results.

  17. Characterization of the dominant structural vibration of hearing aid receivers: Towards the moderation of mechanical feedback in hearing aids

    NASA Astrophysics Data System (ADS)

    Varanda, Brenno R.

    Presented are the results from the experimental, analytical, and computational analyses accomplished to characterize the mechanical vibration of hearing aid receivers, a key electro-acoustic component of hearing aids. The function of a receiver in a hearing aid is to provide an amplified sound signal into the ear canal. Unfortunately, as the receiver produces sound, it also undergoes vibration which can be transmitted through the hearing aid package to the microphones, resulting in undesirable feedback oscillations. To gain more knowledge and control on the source of these feedback oscillations, a dynamic rigid body model of the receiver is proposed. The rigid body model captures the essential dynamic features of the receiver. The model is represented by two hinged rigid bodies, under an equal and opposite dynamic moment load, and connected to each other by a torsional spring and damper. The mechanical coupling ratio between the two rigid bodies is proved to be acoustically independent. A method is introduced to estimate the parameters for the proposed model using experimental data. An equivalent finite element analysis model is established and tested against a known and characterized mechanical attachment. The simulated model successfully predicts the structural dynamic response showing excellent agreement between the finite element analysis and measured results.

  18. Pepper CabZIP63 acts as a positive regulator during Ralstonia solanacearum or high temperature-high humidity challenge in a positive feedback loop with CaWRKY40.

    PubMed

    Shen, Lei; Liu, Zhiqin; Yang, Sheng; Yang, Tong; Liang, Jiaqi; Wen, Jiayu; Liu, Yanyan; Li, Jiazhi; Shi, Lanping; Tang, Qian; Shi, Wei; Hu, Jiong; Liu, Cailing; Zhang, Yangwen; Lin, Wei; Wang, Rongzhang; Yu, Huanxin; Mou, Shaoliang; Hussain, Ansar; Cheng, Wei; Cai, Hanyang; He, Li; Guan, Deyi; Wu, Yang; He, Shuilin

    2016-04-01

    CaWRKY40 is known to act as a positive regulator in the response of pepper (Capsicum annuum) to Ralstonia solanacearum inoculation (RSI) or high temperature-high humidity (HTHH), but the underlying mechanism remains elusive. Herein, we report that CabZIP63, a pepper bZIP family member, participates in this process by regulating the expression of CaWRKY40. CabZIP63 was found to localize in the nuclei, be up-regulated by RSI or HTHH, bind to promoters of both CabZIP63(pCabZIP63) and CaWRKY40(pCaWRKY40), and activate pCabZIP63- and pCaWRKY40-driven β-glucuronidase expression in a C- or G-box-dependent manner. Silencing of CabZIP63 by virus-induced gene silencing (VIGS) in pepper plants significantly attenuated their resistance to RSI and tolerance to HTHH, accompanied by down-regulation of immunity- or thermotolerance-associated CaPR1, CaNPR1, CaDEF1, and CaHSP24. Hypersensitive response-mediated cell death and expression of the tested immunity- and thermotolerance-associated marker genes were induced by transient overexpression (TOE) of CabZIP63, but decreased by that of CabZIP63-SRDX. Additionally, binding of CabZIP63 to pCaWRKY40 was up-regulated by RSI or HTHH, and the transcript level of CaWRKY40 and binding of CaWRKY40 to the promoters of CaPR1, CaNPR1, CaDEF1 and CaHSP24 were up-regulated by TOE of CabZIP63. On the other hand, CabZIP63 was also up-regulated transcriptionally by TOE of CaWRKY40. The data suggest collectively that CabZIP63 directly or indirectly regulates the expression of CaWRKY40 at both the transcriptional and post-transcriptional level, forming a positive feedback loop with CaWRKY40 during pepper's response to RSI or HTHH. Altogether, our data will help to elucidate the underlying mechanism of crosstalk between pepper's response to RSI and HTHH. PMID:26936828

  19. Pepper CabZIP63 acts as a positive regulator during Ralstonia solanacearum or high temperature–high humidity challenge in a positive feedback loop with CaWRKY40

    PubMed Central

    Shen, Lei; Liu, Zhiqin; Yang, Sheng; Yang, Tong; Liang, Jiaqi; Wen, Jiayu; Liu, Yanyan; Li, Jiazhi; Shi, Lanping; Tang, Qian; Shi, Wei; Hu, Jiong; Liu, Cailing; Zhang, Yangwen; Lin, Wei; Wang, Rongzhang; Yu, Huanxin; Mou, Shaoliang; Hussain, Ansar; Cheng, Wei; Cai, Hanyang; He, Li; Guan, Deyi; Wu, Yang; He, Shuilin

    2016-01-01

    CaWRKY40 is known to act as a positive regulator in the response of pepper (Capsicum annuum) to Ralstonia solanacearum inoculation (RSI) or high temperature–high humidity (HTHH), but the underlying mechanism remains elusive. Herein, we report that CabZIP63, a pepper bZIP family member, participates in this process by regulating the expression of CaWRKY40. CabZIP63 was found to localize in the nuclei, be up-regulated by RSI or HTHH, bind to promoters of both CabZIP63 (pCabZIP63) and CaWRKY40 (pCaWRKY40), and activate pCabZIP63- and pCaWRKY40-driven β-glucuronidase expression in a C- or G-box-dependent manner. Silencing of CabZIP63 by virus-induced gene silencing (VIGS) in pepper plants significantly attenuated their resistance to RSI and tolerance to HTHH, accompanied by down-regulation of immunity- or thermotolerance-associated CaPR1, CaNPR1, CaDEF1, and CaHSP24. Hypersensitive response-mediated cell death and expression of the tested immunity- and thermotolerance-associated marker genes were induced by transient overexpression (TOE) of CabZIP63, but decreased by that of CabZIP63-SRDX. Additionally, binding of CabZIP63 to pCaWRKY40 was up-regulated by RSI or HTHH, and the transcript level of CaWRKY40 and binding of CaWRKY40 to the promoters of CaPR1, CaNPR1, CaDEF1 and CaHSP24 were up-regulated by TOE of CabZIP63. On the other hand, CabZIP63 was also up-regulated transcriptionally by TOE of CaWRKY40. The data suggest collectively that CabZIP63 directly or indirectly regulates the expression of CaWRKY40 at both the transcriptional and post-transcriptional level, forming a positive feedback loop with CaWRKY40 during pepper’s response to RSI or HTHH. Altogether, our data will help to elucidate the underlying mechanism of crosstalk between pepper’s response to RSI and HTHH. PMID:26936828

  20. High-affinity cholecystokinin type A receptor/cytosolic phospholipase A2 pathways mediate Ca2+ oscillations via a positive feedback regulation by calmodulin kinase in pancreatic acini.

    PubMed

    Lankisch, T O; Nozu, F; Owyang, C; Tsunoda, Y

    1999-09-01

    In rat pancreatic acini, we previously demonstrated that depending on the agonist used, activation of cholecystokinin type A (CCKA) receptor (CCK-AR) results in the differential involvement of the cytosolic phospholipase A2 (cPLA2), phospholipase Cbeta1 (PLCbeta1) and Src/protein tyrosine kinase (PTK) pathways. The high-affinity CCK-AR appears to be coupled to the Gbeta/cPLA2/arachidonic acid (AA) cascade in mediating Ca2+ oscillations. The low-affinity CCK-AR is coupled to both the Galphaq/11/PLCbeta1/inositol 1,4,5-trisphosphate (IP3) to evoke intracellular Ca2+ release and the Src/PTK pathway to mediate extracellular Ca2+ influx. The objectives of this study were to provide evidence that cPLA2 is present in pancreatic acini and to evaluate the possibility that its activation results in Ca2+ oscillations and amylase secretion. Furthermore, we investigated the mechanism of Ca2+ oscillations mediated by the high-affinity CCK-AR. In rat pancreatic acini, immunoprecipitation studies using an anti-cPLA2 monoclonal antibody, demonstrated a cPLA2 band at the location of 110 kDa. A selective inhibitor of cPLA2, AACOCF3 (100 microM), inhibited production of AA metabolites, Ca2+ oscillations and amylase secretion elicited by the high-affinity CCK-AR agonist, CCK-OPE (10-1000 nM). In addition, through the repetitive release of intracellular Ca2+, CCK-OPE enhanced phosphotransferase activities of Ca2+/calmodulin-dependent protein kinase type IV (CaMK IV), which were inhibited by AACOCF3. The CaMK inhibitor, K252-a (1-3 microM), also abolished basal and CCK-OPE-stimulated CaMK IV activities. The CaM inhibitor, W-7 (100 microM), and K252-a inhibited Ca2+ oscillations and amylase secretion evoked by CCK-OPE without affecting the AA formation. Therefore, it appears that Ca2+ oscillations elicited by the high-affinity CCK-AR/Gbeta/cPLA2/AA pathway activate CaMK IV. Activated CaMK, in turn, regulates Ca2+ oscillations through a positive feedback mechanism to mediate pancreatic

  1. The interleukin-6 and noradrenaline mediated inflammation-stress feedback mechanism is dysregulated in metabolic syndrome: Effect of exercise

    PubMed Central

    2011-01-01

    Background Metabolic syndrome (MS) is a metabolic disorder associated with obesity, type-II diabetes, and "low grade inflammation", with the concomitant increased risk of cardiovascular events. Removal of the inflammatory mediator signals is a promising strategy to protect against insulin resistance, obesity, and other problems associated with MS such as cardiovascular disease. The aim of the present investigation was to determine the "inflammatory and stress status" in an experimental model of MS, and to evaluate the effect of a program of habitual exercise and the resulting training-induced adaptation to the effects of a single bout of acute exercise. Methods Obese Zucker rats (fa/fa) were used as the experimental model of MS, and lean Zucker rats (Fa/fa) were used for reference values. The habitual exercise (performed by the obese rats) consisted of treadmill running: 5 days/week for 14 weeks, at 35 cm/s for 35 min in the last month. The acute exercise consisted of a single session of 25-35 min at 35 cm/s. Circulating concentrations of IL-6 (a cytokine that regulates the inflammatory and metabolic responses), CRP (a systemic inflammatory marker), and corticosterone (CTC) (the main glucocorticoid in rats) were determined by ELISA, and that of noradrenaline (NA) was determined by HPLC. Glucose was determined by standard methods. Results The genetically obese animals showed higher circulating levels of glucose, IL-6, PCR, and NA compared with the control lean animals. The habitual exercise program increased the concentration of IL-6, PCR, NA, and glucose, but decreased that of CTC. Acute exercise increased IL-6, CRP, and NA in the sedentary obese animals, but not in the trained obese animals. CTC was increased after the acute exercise in the trained animals only. Conclusion Animals with MS present a dysregulation in the feedback mechanism between IL-6 and NA which can contribute to the systemic low-grade inflammation and/or hyperglycaemia of MS. An inappropriate

  2. The role of mRNA and protein stability in the function of coupled positive and negative feedback systems in eukaryotic cells.

    PubMed

    Moss Bendtsen, Kristian; Jensen, Mogens H; Krishna, Sandeep; Semsey, Szabolcs

    2015-01-01

    Oscillators and switches are important elements of regulation in biological systems. These are composed of coupling negative feedback loops, which cause oscillations when delayed, and positive feedback loops, which lead to memory formation. Here, we examine the behavior of a coupled feedback system, the Negative Autoregulated Frustrated bistability motif (NAF). This motif is a combination of two previously explored motifs, the frustrated bistability motif (FBM) and the negative auto regulation motif (NAR), which both can produce oscillations. The NAF motif was previously suggested to govern long term memory formation in animals, and was used as a synthetic oscillator in bacteria. We build a mathematical model to analyze the dynamics of the NAF motif. We show analytically that the NAF motif requires an asymmetry in the strengths of activation and repression links in order to produce oscillations. We show that the effect of time delays in eukaryotic cells, originating from mRNA export and protein import, are negligible in this system. Based on the reported protein and mRNA half-lives in eukaryotic cells, we find that even though the NAF motif possesses the ability for oscillations, it mostly promotes constant protein expression at the biologically relevant parameter regimes. PMID:26365394

  3. The role of mRNA and protein stability in the function of coupled positive and negative feedback systems in eukaryotic cells

    PubMed Central

    Moss Bendtsen, Kristian; Jensen, Mogens H.; Krishna, Sandeep; Semsey, Szabolcs

    2015-01-01

    Oscillators and switches are important elements of regulation in biological systems. These are composed of coupling negative feedback loops, which cause oscillations when delayed, and positive feedback loops, which lead to memory formation. Here, we examine the behavior of a coupled feedback system, the Negative Autoregulated Frustrated bistability motif (NAF). This motif is a combination of two previously explored motifs, the frustrated bistability motif (FBM) and the negative auto regulation motif (NAR), which both can produce oscillations. The NAF motif was previously suggested to govern long term memory formation in animals, and was used as a synthetic oscillator in bacteria. We build a mathematical model to analyze the dynamics of the NAF motif. We show analytically that the NAF motif requires an asymmetry in the strengths of activation and repression links in order to produce oscillations. We show that the effect of time delays in eukaryotic cells, originating from mRNA export and protein import, are negligible in this system. Based on the reported protein and mRNA half-lives in eukaryotic cells, we find that even though the NAF motif possesses the ability for oscillations, it mostly promotes constant protein expression at the biologically relevant parameter regimes. PMID:26365394

  4. Three-dimensional MHD Magnetic Reconnection Simulations with a Finite Guide Field: Proposal of the Shock-evoking Positive-feedback Model

    NASA Astrophysics Data System (ADS)

    Wang, Shuoyang; Yokoyama, Takaaki; Isobe, Hiroaki

    2015-09-01

    Using a three-dimensional (3D) magnetohydrodynamic model, we simulate the magnetic reconnection in a single current sheet. We assume a finite guide field, a random perturbation on the velocity field, and uniform resistivity. Our model enhances the reconnection rate relative to the classical Sweet-Parker model in the same configuration. The efficiency of magnetic energy conversion is increased by interactions between the multiple tearing layers coexisting in the global current sheet. This interaction, which forms a positive-feedback system, arises from coupling of the inflow and outflow regions in different layers across the current sheet. The coupling accelerates the elementary reconnection events, thereby enhancing the global reconnection rate. The reconnection establishes flux tubes along each tearing layer. Slow-mode shocks gradually form along the outer boundaries of these tubes, further accelerating the magnetic energy conversion. Such a positive-feedback system is absent in two-dimensional simulations, 3D reconnection without a guide field, and reconnection under a single perturbation mode. We refer to our model as the “shock-evoking positive-feedback” model.

  5. Getting into position: the catalytic mechanisms of protein ubiquitylation.

    PubMed Central

    Passmore, Lori A; Barford, David

    2004-01-01

    The role of protein ubiquitylation in the control of diverse cellular pathways has recently gained widespread attention. Ubiquitylation not only directs the targeted destruction of tagged proteins by the 26 S proteasome, but it also modulates protein activities, protein-protein interactions and subcellular localization. An understanding of the components involved in protein ubiquitylation (E1s, E2s and E3s) is essential to understand how specificity and regulation are conferred upon these pathways. Much of what we know about the catalytic mechanisms of protein ubiquitylation comes from structural studies of the proteins involved in this process. Indeed, structures of ubiquitin-activating enzymes (E1s) and ubiquitin-conjugating enzymes (E2s) have provided insight into their mechanistic details. E3s (ubiquitin ligases) contain most of the substrate specificity and regulatory elements required for protein ubiquitylation. Although several E3 structures are available, the specific mechanistic role of E3s is still unclear. This review will discuss the different types of ubiquitin signals and how they are generated. Recent advances in the field of protein ubiquitylation will be examined, including the mechanisms of E1, E2 and E3. In particular, we discuss the complexity of molecular recognition required to impose selectivity on substrate selection and topology of poly-ubiquitin chains. PMID:14998368

  6. Feedback Amplification of Neutrophil Function.

    PubMed

    Németh, Tamás; Mócsai, Attila

    2016-06-01

    As the first line of innate immune defense, neutrophils need to mount a rapid and robust antimicrobial response. Recent studies implicate various positive feedback amplification processes in achieving that goal. Feedback amplification ensures effective migration of neutrophils in shallow chemotactic gradients, multiple waves of neutrophil recruitment to the site of inflammation, and the augmentation of various effector functions of the cells. We review here such positive feedback loops including intracellular and autocrine processes, paracrine effects mediated by lipid (LTB4), chemokine, and cytokine mediators, and bidirectional interactions with the complement system and with other immune and non-immune cells. These amplification mechanisms are not only involved in antimicrobial immunity but also contribute to neutrophil-mediated tissue damage under pathological conditions. PMID:27157638

  7. Audio Feedback -- Better Feedback?

    ERIC Educational Resources Information Center

    Voelkel, Susanne; Mello, Luciane V.

    2014-01-01

    National Student Survey (NSS) results show that many students are dissatisfied with the amount and quality of feedback they get for their work. This study reports on two case studies in which we tried to address these issues by introducing audio feedback to one undergraduate (UG) and one postgraduate (PG) class, respectively. In case study one…

  8. Effect of foot position on balance ability in single-leg stance with and without visual feedback.

    PubMed

    Schneiders, Anthony; Gregory, Kate; Karas, Steve; Mündermann, Annegret

    2016-06-14

    The purpose of this study was to determine the natural foot position and to quantify the effect of foot position on balance performance during single-leg stance. Forty healthy subjects participated in this study (age, 18 to 32 years; 24 female). Subjects were asked to perform single-leg balance trials on a balance force plate in their self-selected and four predetermined foot positions with their eyes open and closed. Sway distance, area and velocity were computed for each trial. There was significant interactions between visual conditions and foot position for all sway parameters (P<.001). With the eyes closed, sway parameters were greatest for the self-selected foot position compared to the other foot positions (P<.005). No differences in sway parameters between foot positions were detected for the eyes-open condition. Sway distance, area and velocity were 94%, 400% and 89% greater, respectively, for the eyes-closed than the eyes-open condition. Self-selected foot placement did not produce the most stable single-leg stance. The results of this study indicate that foot position is not important for protocols for assessing balance or for rehabilitation exercises using eyes-open conditions and that assessment protocols and rehabilitation exercises should clearly specify the foot position when using eyes-closed protocols. PMID:27156374

  9. Phytotoxicity of salt and plant salt uptake: Modeling ecohydrological feedback mechanisms

    NASA Astrophysics Data System (ADS)

    Bauer-Gottwein, Peter; Rasmussen, Nikolaj F.; Feificova, Dagmar; Trapp, Stefan

    2008-04-01

    A new model of phytotoxicity of salt and plant salt uptake is presented and is coupled to an existing three-dimensional groundwater simulation model. The implementation of phytotoxicity and salt uptake relationships is based on experimental findings from willow trees grown in hydroponic solution. The data confirm an s-shaped phytotoxicity relationship as found in previous studies. Uptake data were explained assuming steady state salt concentration in plant roots, passive salt transport into the roots, and active enzymatic removal of salt from plant roots. On the one hand, transpiration strongly depends on groundwater salinity (phytotoxicity); on the other hand, transpiration significantly changes the groundwater salinity (uptake). This feedback loop generates interesting dynamic phenomena in hydrological systems that are dominated by transpiration and are influenced by significant salinity gradients. Generic simulations are performed for the Okavango island system and are shown to reproduce essential phenomena observed in nature.

  10. Model Predicts That MKP1 and TAB1 Regulate p38α Nuclear Pulse and Its Basal Activity through Positive and Negative Feedback Loops in Response to IL-1

    PubMed Central

    Singh, Raghvendra

    2016-01-01

    Interleukin-1 mediates inflammation and stress response through nuclear activity of p38α. Although IL-1 receptor is not degraded, p38α activation is transient. IL-1 also causes cell migration and EMT by modulating cell-cell junctions. Although molecules involved in p38 activation are known, mechanism of the transient nuclear response and its basal activity remains unknown. By mathematical modeling of IL1/p38 signaling network, we show that IL-1 induces robust p38α activation both in the nucleus and in the cytoplasm/membrane. While nuclear response consists of an acute phase, membrane response resembles a step change. Following stimulation, p38α activity returns to a basal level in absence of receptor degradation. While nuclear pulse is controlled by MKP1 through a negative feedback to pp38, its basal activity is controlled by both TAB1 and MKP1 through a positive feedback loop. Our model provides insight into the mechanism of p38α activation, reason for its transient nuclear response, and explanation of the basal activity of MKK3/6 and p38α, which has been experimentally observed by other groups. PMID:27314954

  11. Positioning.

    ERIC Educational Resources Information Center

    Conone, Ruth M.

    The key to positioning is the creation of a clear benefit image in the consumer's mind. One positioning strategy is creating in the prospect's mind a position that takes into consideration the company's or agency's strengths and weaknesses as well as those of its competitors. Another strategy is to gain entry into a position ladder owned by…

  12. Glacier-surge mechanisms promoted by a hydro-thermodynamic feedback to summer melt

    NASA Astrophysics Data System (ADS)

    Dunse, T.; Schellenberger, T.; Hagen, J. O.; Kääb, A.; Schuler, T. V.; Reijmer, C. H.

    2015-02-01

    Mass loss from glaciers and ice sheets currently accounts for two-thirds of the observed global sea-level rise and has accelerated since the 1990s, coincident with strong atmospheric warming in the polar regions. Here we present continuous GPS measurements and satellite synthetic-aperture-radar-based velocity maps from Basin-3, the largest drainage basin of the Austfonna ice cap, Svalbard. Our observations demonstrate strong links between surface-melt and multiannual ice-flow acceleration. We identify a hydro-thermodynamic feedback that successively mobilizes stagnant ice regions, initially frozen to their bed, thereby facilitating fast basal motion over an expanding area. By autumn 2012, successive destabilization of the marine terminus escalated in a surge of Basin-3. The resulting iceberg discharge of 4.2±1.6 Gt a-1 over the period April 2012 to May 2013 triples the calving loss from the entire ice cap. With the seawater displacement by the terminus advance accounted for, the related sea-level rise contribution amounts to 7.2±2.6 Gt a-1. This rate matches the annual ice-mass loss from the entire Svalbard archipelago over the period 2003-2008, highlighting the importance of dynamic mass loss for glacier mass balance and sea-level rise. The active role of surface melt, i.e. external forcing, contrasts with previous views of glacier surges as purely internal dynamic instabilities. Given sustained climatic warming and rising significance of surface melt, we propose a potential impact of the hydro-thermodynamic feedback on the future stability of ice-sheet regions, namely at the presence of a cold-based marginal ice plug that restricts fast drainage of inland ice. The possibility of large-scale dynamic instabilities such as the partial disintegration of ice sheets is acknowledged but not quantified in global projections of sea-level rise.

  13. Mechanism of Positive Allosteric Modulators Acting on AMPA Receptors

    SciTech Connect

    Jin,R.; Clark, S.; Weeks, A.; Dudman, J.; Gouaux, E.; Partin, K.

    2005-01-01

    Ligand-gated ion channels involved in the modulation of synaptic strength are the AMPA, kainate, and NMDA glutamate receptors. Small molecules that potentiate AMPA receptor currents relieve cognitive deficits caused by neurodegenerative diseases such as Alzheimer's disease and show promise in the treatment of depression. Previously, there has been limited understanding of the molecular mechanism of action for AMPA receptor potentiators. Here we present cocrystal structures of the glutamate receptor GluR2 S1S2 ligand-binding domain in complex with aniracetam [1-(4-methoxybenzoyl)-2-pyrrolidinone] or CX614 (pyrrolidino-1, 3-oxazino benzo-1, 4-dioxan-10-one), two AMPA receptor potentiators that preferentially slow AMPA receptor deactivation. Both potentiators bind within the dimer interface of the nondesensitized receptor at a common site located on the twofold axis of molecular symmetry. Importantly, the potentiator binding site is adjacent to the 'hinge' in the ligand-binding core 'clamshell' that undergoes conformational rearrangement after glutamate binding. Using rapid solution exchange, patch-clamp electrophysiology experiments, we show that point mutations of residues that interact with potentiators in the cocrystal disrupt potentiator function. We suggest that the potentiators slow deactivation by stabilizing the clamshell in its closed-cleft, glutamate-bound conformation.

  14. Cloud CCN feedback

    SciTech Connect

    Hudson, J.G.

    1992-12-31

    Cloud microphysics affects cloud albedo precipitation efficiency and the extent of cloud feedback in response to global warming. Compared to other cloud parameters, microphysics is unique in its large range of variability and the fact that much of the variability is anthropogenic. Probably the most important determinant of cloud microphysics is the spectra of cloud condensation nuclei (CCN) which display considerable variability and have a large anthropogenic component. When analyzed in combination three field observation projects display the interrelationship between CCN and cloud microphysics. CCN were measured with the Desert Research Institute (DRI) instantaneous CCN spectrometer. Cloud microphysical measurements were obtained with the National Center for Atmospheric Research Lockheed Electra. Since CCN and cloud microphysics each affect the other a positive feedback mechanism can result.

  15. EB-virus latent membrane protein 1 potentiates the stemness of nasopharyngeal carcinoma via preferential activation of PI3K/AKT pathway by a positive feedback loop.

    PubMed

    Yang, C-F; Yang, G-D; Huang, T-J; Li, R; Chu, Q-Q; Xu, L; Wang, M-S; Cai, M-D; Zhong, L; Wei, H-J; Huang, H-B; Huang, J-L; Qian, C-N; Huang, B-J

    2016-06-30

    Our previous study reported that Epstein-Barr virus(EBV)-encoded latent membrane protein 1 (LMP1) could induce development of CD44(+/High) stem-like cells in nasopharyngeal carcinoma (NPC). However, the molecular mechanisms that underlie modulation of cancer stem cells (CSCs) in NPC remain unclear. Here, we show that LMP1 induced CSC-like properties through promotion of the expression of epithelial-mesenchymal transition-like cellular markers and through alterations in differentiation markers. Furthermore, LMP1 activated and triggered phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway, which subsequently stimulated expression of CSC markers, development of side population and tumor sphere formation. This suggests that PI3K/AKT pathway has an important role in the induction and maintenance of CSC properties in NPC. Similarly, PI3K/AKT pathway was also activated by phosphorylase in LMP1-induced CD44(+/High) cells. In addition, LMP1 greatly increased expression of miR-21 and downregulated expression of the miR-21 target, PTEN. Overexpression of miR-21 by transfection of miR-21 mimics into LMP1-transformed cells led to phosphorylase-mediated activation of the PI3K/AKT pathway and induction of CSCs. On the contrary, phosphorylation of the PI3K/AKT pathway and the expression of CSC were reversed by an miR-21 inhibitor. The specific inhibitor (Ly294002) of PI3K/AKT pathway significantly decreased expression of miR-21 and CSC markers and upregulated the expression of PTEN, which indicates that miR-21 and PTEN are the downstream effectors of PI3K/AKT and that expression of these two effectors are related to the development of NPC CSCs. Taken together, our novel findings indicate that LMP1, PI3K/AKT, miR-21 and PTEN constitute a positive feedback loop and have a key role in LMP1-induced CSCs in NPC. PMID:26568302

  16. Convection and the Soil-Moisture Precipitation Feedback

    NASA Astrophysics Data System (ADS)

    Schar, C.; Froidevaux, P.; Keller, M.; Schlemmer, L.; Langhans, W.; Schmidli, J.

    2014-12-01

    The soil moisture - precipitation (SMP) feedback is of key importance for climate and climate change. A positive SMP feedback tends to amplify the hydrological response to external forcings (and thereby fosters precipitation and drought extremes), while a negative SMP feedback tends to moderate the influence of external forcings (and thereby stabilizes the hydrological cycle). The sign of the SMP feedback is poorly constrained by the current literature. Theoretical, modeling and observational studies partly disagree, and have suggested both negative and positive feedback loops. Can wet soil anomalies indeed result in either an increase or a decrease of precipitation (positive or negative SMP feedback, respectively)? Here we investigate the local SMP feedback using real-case and idealized convection-resolving simulations. An idealized simulation strategy is developed, which is able to replicate both signs of the feedback loop, depending on the environmental parameters. The mechanism relies on horizontal soil moisture variations, which may develop and intensify spontaneously. The positive expression of the feedback is associated with the initiation of convection over dry soil patches, but the convective cells then propagate over wet patches, where they strengthen and preferentially precipitate. The negative feedback may occur when the wind profile is too weak to support the propagation of convective features from dry to wet areas. Precipitation is then generally weaker and falls preferentially over dry patches. The results highlight the role of the mid-tropospheric flow in determining the sign of the feedback. A key element of the positive feedback is the exploitation of both low convective inhibition (CIN) over dry patches (for the initiation of convection), and high CAPE over wet patches (for the generation of precipitation). The results of this study will also be discussed in relation to climate change scenarios that exhibit large biases in surface temperature and

  17. An Adapting Auditory-motor Feedback Loop Can Contribute to Generating Vocal Repetition.

    PubMed

    Wittenbach, Jason D; Bouchard, Kristofer E; Brainard, Michael S; Jin, Dezhe Z

    2015-10-01

    Consecutive repetition of actions is common in behavioral sequences. Although integration of sensory feedback with internal motor programs is important for sequence generation, if and how feedback contributes to repetitive actions is poorly understood. Here we study how auditory feedback contributes to generating repetitive syllable sequences in songbirds. We propose that auditory signals provide positive feedback to ongoing motor commands, but this influence decays as feedback weakens from response adaptation during syllable repetitions. Computational models show that this mechanism explains repeat distributions observed in Bengalese finch song. We experimentally confirmed two predictions of this mechanism in Bengalese finches: removal of auditory feedback by deafening reduces syllable repetitions; and neural responses to auditory playback of repeated syllable sequences gradually adapt in sensory-motor nucleus HVC. Together, our results implicate a positive auditory-feedback loop with adaptation in generating repetitive vocalizations, and suggest sensory adaptation is important for feedback control of motor sequences. PMID:26448054

  18. An Adapting Auditory-motor Feedback Loop Can Contribute to Generating Vocal Repetition

    PubMed Central

    Brainard, Michael S.; Jin, Dezhe Z.

    2015-01-01

    Consecutive repetition of actions is common in behavioral sequences. Although integration of sensory feedback with internal motor programs is important for sequence generation, if and how feedback contributes to repetitive actions is poorly understood. Here we study how auditory feedback contributes to generating repetitive syllable sequences in songbirds. We propose that auditory signals provide positive feedback to ongoing motor commands, but this influence decays as feedback weakens from response adaptation during syllable repetitions. Computational models show that this mechanism explains repeat distributions observed in Bengalese finch song. We experimentally confirmed two predictions of this mechanism in Bengalese finches: removal of auditory feedback by deafening reduces syllable repetitions; and neural responses to auditory playback of repeated syllable sequences gradually adapt in sensory-motor nucleus HVC. Together, our results implicate a positive auditory-feedback loop with adaptation in generating repetitive vocalizations, and suggest sensory adaptation is important for feedback control of motor sequences. PMID:26448054

  19. A review of the mechanisms by which attentional feedback shapes visual selectivity.

    PubMed

    Ling, Sam; Jehee, Janneke F M; Pestilli, Franco

    2015-01-01

    The glut of information available for the brain to process at any given moment necessitates an efficient attentional system that can 'pick and choose' what information receives prioritized processing. A growing body of work, spanning numerous methodologies and species, reveals that one powerful way in which attending to an item separates the wheat from the chaff is by altering a basic response property in the brain: neuronal selectivity. Selectivity is a cornerstone response property, largely dictating our ability to represent and interact with the environment. Although it is likely that selectivity is altered throughout many brain areas, here we focus on how directing attention to an item affects selectivity in the visual system, where this response property is generally more well characterized. First, we review the neural architecture supporting selectivity, and then discuss the various changes that could occur in selectivity for an attended item. In a survey of the literature, spanning neurophysiology, neuroimaging and psychophysics, we reveal that there is general convergence regarding the manner with which selectivity is shaped by attentional feedback. In a nutshell, the literature suggests that the type of changes in selectivity that manifest appears to depend on the type of attention being deployed: whereas directing spatial attention towards an item only alters spatial selectivity, directing feature-based attention can alter the selectivity of attended features. PMID:24990408

  20. Phosphoproteome analysis of the MAPK pathway reveals previously undetected feedback mechanisms.

    PubMed

    Gnad, Florian; Doll, Sophia; Song, Kyung; Stokes, Matthew P; Moffat, John; Liu, Bonnie; Arnott, David; Wallin, Jeffrey; Friedman, Lori S; Hatzivassiliou, Georgia; Belvin, Marcia

    2016-07-01

    The RAS-RAF-MEK-ERK (MAPK) pathway is prevalently perturbed in cancer. Recent large-scale sequencing initiatives profiled thousands of tumors providing insight into alterations at the DNA and RNA levels. These efforts confirmed that key nodes of the MAPK pathway, in particular KRAS and BRAF, are among the most frequently altered proteins in cancer. The establishment of targeted therapies, however, has proven difficult. To decipher the underlying challenges, it is essential to decrypt the phosphorylation network spanned by the MAPK core axis. Using mass spectrometry we identified 2241 phosphorylation sites on 1020 proteins, and measured their responses to inhibition of MEK or ERK. Multiple phosphorylation patterns revealed previously undetected feedback, as upstream signaling nodes, including receptor kinases, showed changes at the phosphorylation level. We provide a dataset rich in potential therapeutic targets downstream of the MAPK cascade. By integrating TCGA (The Cancer Genome Atlas) data, we highlight some downstream phosphoproteins that are frequently altered in cancer. All MS data have been deposited in the ProteomeXchange with identifier PXD003908 (http://proteomecentral.proteomexchange.org/dataset/PXD003908). PMID:27273156

  1. Models of AGN feedback

    NASA Astrophysics Data System (ADS)

    Combes, Françcoise

    2015-02-01

    The physical processes responsible of sweeping up the surrounding gas in the host galaxy of an AGN, and able in some circumstances to expel it from the galaxy, are not yet well known. The various mechanisms are briefly reviewed: quasar or radio modes, either momentum-conserving outflows, energy-conserving outflows, or intermediate. They are confronted to observations, to know whether they can explain the M-sigma relation, quench the star formation or whether they can also provide some positive feedback and how the black hole accretion history is related to that of star formation.

  2. The Role of Possible Feedback Mechanisms in the Effects of Altered Gravity on Formation and Function of Gravireceptors of Mollusks and Fish

    NASA Technical Reports Server (NTRS)

    Kondrachuk, Alexander V.; Boyle, Richard D.

    2005-01-01

    The variety of the effects of altered gravity (AG) on development and function of gravireceptors cannot be explained by simple feedback mechanism that correlates gravity level and weight of test mass. The reaction of organisms to the change of gravity depends on the phase of their development. To predict this reaction we need to know the details of the mechanisms of gravireceptor formation

  3. Upright position mechanical ventilation: an alternative strategy for ALI/ARDS patients?

    PubMed

    Zhu, Min; Zhang, Wei; Wang, Jia-Ning; Yan, Hua; Li, Yang-Kai; Ai, Bo; Fu, Sheng-Lin; Fu, Xiang-Ning

    2009-11-01

    Use of body positioning to improve oxygenation in mechanically ventilated patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) has been well documented. However, neither prone position ventilation nor side lying ventilation has been reported to improve the survival. Whether there is a body position superior to routine supine position or other positions as therapeutic adjunct for ventilated patients with ALI and ARDS? We propose the hypothesis that upright position ventilation may be helpful to improve oxygenation and benefit patients with ALI/ARDS. According to the existing physiologic and pathophysiologic data of upright position investigation, we suppose that improvement of V/Q matching, increased functional residual capacity, alveolar recruitment, accelerated diaphragm recovery, early gastric emptying and enteric feeding may be a potential protect mechanism of upright position ventilation. Whether this can be translated into improvement in patient outcome should be further tested in clinical trial. PMID:19683402

  4. Acetylcholine Promotes Ca2+and NO-Oscillations in Adipocytes Implicating Ca2+→NO→cGMP→cADP-ribose→Ca2+ Positive Feedback Loop - Modulatory Effects of Norepinephrine and Atrial Natriuretic Peptide

    PubMed Central

    Turovsky, Egor A.; Turovskaya, Mariya V.; Dolgacheva, Ludmila P.; Zinchenko, Valery P.; Dynnik, Vladimir V.

    2013-01-01

    Purpose This study investigated possible mechanisms of autoregulation of Ca2+ signalling pathways in adipocytes responsible for Ca2+ and NO oscillations and switching phenomena promoted by acetylcholine (ACh), norepinephrine (NE) and atrial natriuretic peptide (ANP). Methods Fluorescent microscopy was used to detect changes in Ca2+ and NO in cultures of rodent white adipocytes. Agonists and inhibitors were applied to characterize the involvement of various enzymes and Ca2+-channels in Ca2+ signalling pathways. Results ACh activating M3-muscarinic receptors and Gβγ protein dependent phosphatidylinositol 3 kinase induces Ca2+ and NO oscillations in adipocytes. At low concentrations of ACh which are insufficient to induce oscillations, NE or α1, α2-adrenergic agonists act by amplifying the effect of ACh to promote Ca2+ oscillations or switching phenomena. SNAP, 8-Br-cAMP, NAD and ANP may also produce similar set of dynamic regimes. These regimes arise from activation of the ryanodine receptor (RyR) with the implication of a long positive feedback loop (PFL): Ca2+→ NO→cGMP→cADPR→Ca2+, which determines periodic or steady operation of a short PFL based on Ca2+-induced Ca2+ release via RyR by generating cADPR, a coagonist of Ca2+ at the RyR. Interplay between these two loops may be responsible for the observed effects. Several other PFLs, based on activation of endothelial nitric oxide synthase or of protein kinase B by Ca2+-dependent kinases, may reinforce functioning of main PFL and enhance reliability. All observed regimes are independent of operation of the phospholipase C/Ca2+-signalling axis, which may be switched off due to negative feedback arising from phosphorylation of the inositol-3-phosphate receptor by protein kinase G. Conclusions This study presents a kinetic model of Ca2+-signalling system operating in adipocytes and integrating signals from various agonists, which describes it as multivariable multi feedback network with a family of nested

  5. Effects of chemical feedback on respiratory motor and ventilatory output during different modes of assisted mechanical ventilation.

    PubMed

    Mitrouska, J; Xirouchaki, N; Patakas, D; Siafakas, N; Georgopoulos, D

    1999-04-01

    The purpose of the study was to examine the effects of chemical feedback on respiratory motor and ventilatory output in conscious subjects ventilated on various modes of assisted mechanical ventilation. Seven subjects were connected to a ventilator and randomly ventilated on assist-volume control (AVC), pressure support (PS) or proportional assist ventilation (PAV). On each mode, the assist level was set to the highest comfortable level. Airway and oesophageal (Poes) pressures, tidal volume, respiratory frequency (fR) and end-tidal carbon dioxide tension (PET,CO2) were measured breath-by-breath. When the subjects were stable on each mode, the fraction of inspired carbon dioxide (FI,CO2) was increased stepwise, and changes in minute ventilation (V'E) and respiratory motor output, estimated by the pressure-time product of all the respiratory muscles per breath (PTPrm) and per minute (PTPminute), were observed. At zero FI,CO2, PTPminute/PET,CO2 did not differ between modes, while V'E/ PTPminute was significantly lower with PAV than that with PS and AVC. As a result V'E/PET,CO2 was significantly lower with PAV, preventing, unlike AVC and PS, a significant drop in PET,CO2. With PAV, independent of CO2, V'E/PTPminute remained constant, while it decreased significantly with increasing CO2 stimulus with PS and AVC. At high PET,CO2 respiratory effort was significantly lower with PAV than that with PS and AVC. In conclusion, the mode of mechanical ventilation modifies the effects of chemical feedback on respiratory motor and ventilatory output. At all carbon dioxide stimulus levels neuroventilatory coupling was better preserved with proportional assist ventilation than with pressure support and assist-volume control ventilation. PMID:10362056

  6. The constructed catchment 'Chicken Creek' - a landscape observatory to analyze processes and feedback mechanisms during initial ecosystem development

    NASA Astrophysics Data System (ADS)

    Elmer, Michael; Schaaf, Wolfgang; Gerwin, Werner; Hinz, Christoph

    2014-05-01

    We investigated the initial development of the landscape observatory 'Chicken Creek', Germany, an artificial catchment with well known boundary conditions and inner structures (Gerwin et al., 2011). Over a period of nine years, we observed considerable changes within the site (Elmer et al., 2013). Both internal and external factors could be identified as driving forces for the formation of structures and patterns in the catchment. Over time, secondary structures and patterns evolved and became more and more important. Invading biota and vegetation succession initialized feedback mechanisms resulting in pattern and habitat formation as well as in increased differentiation, heterogeneity and complexity that are typical characteristics of ecosystems (Schaaf et al., 2013). The processes and feedback mechanisms in the initial development of a new landscape may deviate in rates, intensity, and dominance from those known from mature ecosystems. It is therefore crucial to understand these early phases of ecosystem development and to disentangle the increasingly complex interactions between the evolving terrestrial and aquatic, biotic, and abiotic compartments of the system. Elmer M, Gerwin W, Schaaf W, Zaplata MK, Hohberg K, Nenov R, Bens O, Hüttl RF (2013): Dynamics of initial ecosystem development at the artificial catchment Chicken Creek, Lusatia, Germany. Environ Earth Sci 69, 491-505. Gerwin W, Schaaf W, Biemelt D, Winter S, Fischer A, Veste M, Hüttl RF (2011): Overview and first results of ecological monitoring at the artificial watershed Chicken Creek (Germany). Phys Chem Earth 36, 61-73. Schaaf W, Elmer M, Fischer A, Gerwin W, Nenov R, Pretsch H, Seifert S, Winter S, Zaplata MK (2013): Monitoring the formation of structures and patterns during initial development of an artificial catchment. Environ Monit Assess 185, 5965-5986.

  7. Mechanical Cell-Matrix Feedback Explains Pairwise and Collective Endothelial Cell Behavior In Vitro

    PubMed Central

    LaValley, Danielle J.; Reinhart-King, Cynthia A.; Merks, Roeland M. H.

    2014-01-01

    In vitro cultures of endothelial cells are a widely used model system of the collective behavior of endothelial cells during vasculogenesis and angiogenesis. When seeded in an extracellular matrix, endothelial cells can form blood vessel-like structures, including vascular networks and sprouts. Endothelial morphogenesis depends on a large number of chemical and mechanical factors, including the compliancy of the extracellular matrix, the available growth factors, the adhesion of cells to the extracellular matrix, cell-cell signaling, etc. Although various computational models have been proposed to explain the role of each of these biochemical and biomechanical effects, the understanding of the mechanisms underlying in vitro angiogenesis is still incomplete. Most explanations focus on predicting the whole vascular network or sprout from the underlying cell behavior, and do not check if the same model also correctly captures the intermediate scale: the pairwise cell-cell interactions or single cell responses to ECM mechanics. Here we show, using a hybrid cellular Potts and finite element computational model, that a single set of biologically plausible rules describing (a) the contractile forces that endothelial cells exert on the ECM, (b) the resulting strains in the extracellular matrix, and (c) the cellular response to the strains, suffices for reproducing the behavior of individual endothelial cells and the interactions of endothelial cell pairs in compliant matrices. With the same set of rules, the model also reproduces network formation from scattered cells, and sprouting from endothelial spheroids. Combining the present mechanical model with aspects of previously proposed mechanical and chemical models may lead to a more complete understanding of in vitro angiogenesis. PMID:25121971

  8. RHIC 10 Hz global orbit feedback system

    SciTech Connect

    Michnoff, R.; Arnold, L.; Carboni, L.; Cerniglia, P; Curcio, A.; DeSanto, L.; Folz, C.; Ho, C.; Hoff, L.; Hulsart, R.; Karl, R.; Luo, Y.; Liu, C.; MacKay, W.; Mahler, G.; Meng, W.; Mernick, K.; Minty, M.; Montag, C.; Olsen, R.; Piacentino, J.; Popken, P.; Przybylinski, R.; Ptitsyn, V.; Ritter, J.; Schoenfeld, R.; Thieberger, P.; Tuozzolo, J.; Weston, A.; White, J.; Ziminski, P.; Zimmerman, P.

    2011-03-28

    Vibrations of the cryogenic triplet magnets at the Relativistic Heavy Ion Collider (RHIC) are suspected to be causing the horizontal beam perturbations observed at frequencies around 10 Hz. Several solutions to counteract the effect have been considered in the past, including a local beam feedback system at each of the two experimental areas, reinforcing the magnet base support assembly, and a mechanical servo feedback system. However, the local feedback system was insufficient because perturbation amplitudes outside the experimental areas were still problematic, and the mechanical solutions are very expensive. A global 10 Hz orbit feedback system consisting of 36 beam position monitors (BPMs) and 12 small dedicated dipole corrector magnets in each of the two 3.8 km circumference counter-rotating rings has been developed and commissioned in February 2011. A description of the system architecture and results with beam will be discussed.

  9. REG3A accelerates pancreatic cancer cell growth under IL-6-associated inflammatory condition: Involvement of a REG3A-JAK2/STAT3 positive feedback loop.

    PubMed

    Liu, Xiulan; Wang, Jun; Wang, Hongjie; Yin, Guoxiao; Liu, Yang; Lei, Xiang; Xiang, Ming

    2015-06-28

    Regenerating gene protein (REG) 3A is a 19 kD secretory pancreas protein with pro-growth function. Previously we demonstrated that overexpression of REG3A, acting as a key molecule for up-regulation of the JAK2/STAT3 pathway, contributed to inflammation-related pancreatic cancer (PaC) development. However the exact network associated with REG3A signaling still remains unclear. Here we determined that exposure of human PaC cells to cytokine IL-6 activated the oncogenic JAK2/STAT3 pathway, which directly upregulated REG3A expression, accelerated cell cycle progression by promoting CyclinD1 expression, and enhancing the expression of the anti-apoptosis Bcl family. Importantly, the activation of REG3A would instead enhance the JAK2/STAT3 pathway to constitute a REG3A-JAK2/STAT3 positive feedback loop, which leads to the amplification of the oncogenic effects of IL-6/JAK2/STAT3, a classic pathway linking to inflammation-related tumorigenesis, ultimately resulting in PaC cell over-proliferation and tumor formation both in vitro and in vivo. Moreover, EGFR was found to mediate the REG3A signal for PaC cell growth and JAK2/STAT3 activation, thus functioning as a REG3A receptor. Collectively, our results provide the first evidence for the presence of the synergistic effect of REG3A and IL-6 on PaC development via a REG3A-JAK2/STAT3 positive feedback loop. PMID:25779676

  10. Herbivory and Stoichiometric Feedbacks to Primary Production.

    PubMed

    Krumins, Jennifer Adams; Krumins, Valdis; Forgoston, Eric; Billings, Lora; van der Putten, Wim H

    2015-01-01

    Established theory addresses the idea that herbivory can have positive feedbacks on nutrient flow to plants. Positive feedbacks likely emerge from a greater availability of organic carbon that primes the soil by supporting nutrient turnover through consumer and especially microbially-mediated metabolism in the detrital pool. We developed an entirely novel stoichiometric model that demonstrates the mechanism of a positive feedback. In particular, we show that sloppy or partial feeding by herbivores increases detrital carbon and nitrogen allowing for greater nitrogen mineralization and nutritive feedback to plants. The model consists of differential equations coupling flows among pools of: plants, herbivores, detrital carbon and nitrogen, and inorganic nitrogen. We test the effects of different levels of herbivore grazing completion and of the stoichiometric quality (carbon to nitrogen ratio, C:N) of the host plant. Our model analyses show that partial feeding and plant C:N interact because when herbivores are sloppy and plant biomass is diverted to the detrital pool, more mineral nitrogen is available to plants because of the stoichiometric difference between the organisms in the detrital pool and the herbivore. This model helps to identify how herbivory may feedback positively on primary production, and it mechanistically connects direct and indirect feedbacks from soil to plant production. PMID:26098841

  11. Herbivory and Stoichiometric Feedbacks to Primary Production

    PubMed Central

    Krumins, Jennifer Adams; Krumins, Valdis; Forgoston, Eric; Billings, Lora; van der Putten, Wim H.

    2015-01-01

    Established theory addresses the idea that herbivory can have positive feedbacks on nutrient flow to plants. Positive feedbacks likely emerge from a greater availability of organic carbon that primes the soil by supporting nutrient turnover through consumer and especially microbially-mediated metabolism in the detrital pool. We developed an entirely novel stoichiometric model that demonstrates the mechanism of a positive feedback. In particular, we show that sloppy or partial feeding by herbivores increases detrital carbon and nitrogen allowing for greater nitrogen mineralization and nutritive feedback to plants. The model consists of differential equations coupling flows among pools of: plants, herbivores, detrital carbon and nitrogen, and inorganic nitrogen. We test the effects of different levels of herbivore grazing completion and of the stoichiometric quality (carbon to nitrogen ratio, C:N) of the host plant. Our model analyses show that partial feeding and plant C:N interact because when herbivores are sloppy and plant biomass is diverted to the detrital pool, more mineral nitrogen is available to plants because of the stoichiometric difference between the organisms in the detrital pool and the herbivore. This model helps to identify how herbivory may feedback positively on primary production, and it mechanistically connects direct and indirect feedbacks from soil to plant production. PMID:26098841

  12. Molecular basis of the inhibitor selectivity and insights into the feedback inhibition mechanism of citramalate synthase from Leptospira interrogans.

    PubMed

    Zhang, Peng; Ma, Jun; Zhang, Zilong; Zha, Manwu; Xu, Hai; Zhao, Guoping; Ding, Jianping

    2009-07-01

    LiCMS (Leptospira interrogans citramalate synthase) catalyses the first reaction of the isoleucine biosynthesis pathway in L. interrogans, the pathogen of leptospirosis. The catalytic reaction is regulated through feedback inhibition by its end product isoleucine. To understand the molecular basis of the high selectivity of the inhibitor and the mechanism of feedback inhibition, we determined the crystal structure of LiCMSC (C-terminal regulatory domain of LiCMS) in complex with isoleucine, and performed a biochemical study of the inhibition of LiCMS using mutagenesis and kinetic methods. LiCMSC forms a dimer of dimers in both the crystal structure and solution and the dimeric LiCMSC is the basic functional unit. LiCMSC consists of six beta-strands forming two anti-parallel beta-sheets and two alpha-helices and assumes a betaalphabeta three-layer sandwich structure. The inhibitor isoleucine is bound in a pocket at the dimer interface and has both hydrophobic and hydrogen-bonding interactions with several conserved residues of both subunits. The high selectivity of LiCMS for isoleucine over leucine is primarily dictated by the residues, Tyr430, Leu451, Tyr454, Ile458 and Val468, that form a hydrophobic pocket to accommodate the side chain of the inhibitor. The binding of isoleucine has inhibitory effects on the binding of both the substrate, pyruvate, and coenzyme, acetyl-CoA, in a typical pattern of K-type inhibition. The structural and biochemical data from the present study together suggest that the binding of isoleucine affects the binding of the substrate and coenzyme at the active site, possibly via conformational change of the dimer interface of the regulatory domain, leading to inhibition of the catalytic reaction. PMID:19351325

  13. Overall non-linear correction of phase shifting mechanism in white light interferometry system based on displacement feedback control combined with fuzzy PID control

    NASA Astrophysics Data System (ADS)

    Song, Ningfang; Luo, Xinkai; Li, Huipeng; Li, Jiao

    2015-10-01

    The non-linearity of the phase shifting mechanism in white light interferometry system can seriously affect the measuring accuracy of the system. In this paper, the correcting method is to combine the displacement feedback control technology with the fuzzy PID control technology. Displacement feedback control mechanism and fuzzy PID controller are designed and then try to figure it out through Matlab simulation and experiment.. The result shows that combining the displacement feedback control technology with the fuzzy PID control technology can fulfill decent overall non-linear correction in the white light interferometry measuring system. Meanwhile, the accuracy of the correction is high and the non-linearity drop from 2% to 0.1%.

  14. Prestin is an anion transporter dispensable for mechanical feedback amplification in Drosophila hearing.

    PubMed

    Kavlie, Ryan G; Fritz, Janice L; Nies, Florian; Göpfert, Martin C; Oliver, Dominik; Albert, Joerg T; Eberl, Daniel F

    2015-01-01

    In mammals, the membrane-based protein Prestin confers unique electromotile properties to cochlear outer hair cells, which contribute to the cochlear amplifier. Like mammals, the ears of insects, such as those of Drosophila melanogaster, mechanically amplify sound stimuli and have also been reported to express Prestin homologs. To determine whether the D. melanogaster Prestin homolog (dpres) is required for auditory amplification, we generated and analyzed dpres mutant flies. We found that dpres is robustly expressed in the fly's antennal ear. However, dpres mutant flies show normal auditory nerve responses, and intact non-linear amplification. Thus we conclude that, in D. melanogaster, auditory amplification is independent of Prestin. This finding resonates with prior phylogenetic analyses, which suggest that the derived motor function of mammalian Prestin replaced, or amended, an ancestral transport function. Indeed, we show that dpres encodes a functional anion transporter. Interestingly, the acquired new motor function in the phylogenetic lineage leading to birds and mammals coincides with loss of the mechanotransducer channel NompC (=TRPN1), which has been shown to be required for auditory amplification in flies. The advent of Prestin (or loss of NompC, respectively) may thus mark an evolutionary transition from a transducer-based to a Prestin-based mechanism of auditory amplification. PMID:25412730

  15. APEX-CHAMP+ high-J CO observations of low-mass young stellar objects. IV. Mechanical and radiative feedback

    NASA Astrophysics Data System (ADS)

    Yıldız, U. A.; Kristensen, L. E.; van Dishoeck, E. F.; Hogerheijde, M. R.; Karska, A.; Belloche, A.; Endo, A.; Frieswijk, W.; Güsten, R.; van Kempen, T. A.; Leurini, S.; Nagy, Z.; Pérez-Beaupuits, J. P.; Risacher, C.; van der Marel, N.; van Weeren, R. J.; Wyrowski, F.

    2015-04-01

    Context. During the embedded stage of star formation, bipolar molecular outflows and UV radiation from the protostar are important feedback processes. Both processes reflect the accretion onto the forming star and affect subsequent collapse or fragmentation of the cloud. Aims: Our aim is to quantify the feedback, mechanical and radiative, for a large sample of low-mass sources in a consistent manner. The outflow activity is compared to radiative feedback in the form of UV heating by the accreting protostar to search for correlations and evolutionary trends. Methods: Large-scale maps of 26 young stellar objects, which are part of the Herschel WISH key program are obtained using the CHAMP+ instrument on the Atacama Pathfinder EXperiment (12CO and 13CO 6-5; Eup ~ 100 K), and the HARP-B instrument on the James Clerk Maxwell Telescope (12CO and 13CO 3-2; Eup ~ 30 K). The maps have high spatial resolution, particularly the CO 6-5 maps taken with a 9″ beam, resolving the morphology of the outflows. The maps are used to determine outflow parameters and the results are compared with higher-J CO lines obtained with Herschel. Envelope models are used to quantify the amount of UV-heated gas and its temperature from 13CO 6-5 observations. Results: All sources in our sample show outflow activity, with the spatial extent decreasing from the Class 0 to the Class I stage. Consistent with previous studies, the outflow force, FCO, is larger for Class 0 sources than for Class I sources, even if their luminosities are comparable. The outflowing gas typically extends to much greater distances than the power-law envelope and therefore influences the surrounding cloud material directly. Comparison of the CO 6-5 results with HIFI H2O and PACS high-J CO lines, both tracing currently shocked gas, shows that the two components are linked, even though the transitions do not probe the same gas. The link does not extend down to CO 3-2. The conclusion is that CO 6-5 depends on the shock

  16. An Innovative Method of Assessing the Mechanical Axis Deviation in the Lower Limb in Standing Position

    PubMed Central

    Kamath, Jagannath; Jayasheelan, Nikil; Singh, Rohit

    2016-01-01

    Introduction Various methods of measuring mechanical axis deviation of lower limb have been described including radiographic and CT scanogram, intraoperative fluoroscopy with the use of an electrocautery cord. These methods determine the mechanical axis in a supine, non-weight bearing position. Although long cassette standing radiographic view is used for the purpose but is not available at most centres. A dynamic method of determining the mechanical axis in a weight bearing position was devised in this study. Aim The aim of the study was to describe a simpler and newer method in quantifying the mechanical axis deviation in places where full length cassettes for standing X rays are not available. Materials and Methods A pilot study was conducted on 15 patients. The deviation from the mechanical axis was measured using a manually operated, hydraulic mechanism based, elevating scissor lift table. Patient was asked to stand erect over the elevating lift table with both patellae facing forward and C-arm image intensifier was positioned horizontally. Radiological markers were tied to a radio-opaque thread and placed at the centre of head of the femur and another at the centre of the tibio-talar joint. C-arm views of the hip, ankle and knee joint were taken to confirm the correct position of the marker by varying the height of the lift table. Results The mechanical axis deviation values were recorded by measuring distance between the centre of the knee and radio-opaque thread in cm. This was measured in each case both clinically and from the image on the monitor. The two values were found to be statistically same. Pain was measured on VAS. Mechanical axis deviation values and VAS score were found to be positively significantly correlated. Conclusion This technique is dynamic, unique and accurate as compared to other methods for assessing mechanical axis deviation in a weight bearing position. PMID:27504362

  17. Tongxinluo inhibits vascular inflammation and neointimal hyperplasia through blockade of the positive feedback loop between miR-155 and TNF-α.

    PubMed

    Zhang, Ruo-nan; Zheng, Bin; Li, Li-min; Zhang, Jing; Zhang, Xin-hua; Wen, Jin-kun

    2014-08-15

    Tongxinluo (TXL), a traditional Chinese medicine, has multiple vasoprotective effects, including anti-inflammation. MicroRNA-155 (miR-155) is involved in vascular inflammation and atherosclerosis. However, a direct relationship between TXL and miR-155 in the development of vascular inflammation and remodeling had not yet been shown. The objective of the present study was to investigate whether TXL exerts an inhibitory effect on the vascular inflammatory response and neointimal hyperplasia by regulating miR-155 expression. Using the carotid artery ligation model in mice, we have shown that TXL dose dependently inhibited neointimal formation and reduced the vascular inflammatory response by inhibiting inflammatory cytokine production and macrophage infiltration. miR-155 was induced by carotid artery ligation, and neointimal hyperplasia was strongly reduced in miR-155(−/−) mice. In contrast, miR-155 overexpression partly reversed the inhibitory effect of TXL on neointimal hyperplasia. In bone marrow-derived macrophages, miR-155 and TNF-α formed a positive feedback loop to promote the inflammatory response, which could be blocked by TXL. Furthermore, TXL increased Akt1 protein expression and phosphorylation in TNF-α-stimulated marrow-derived macrophages, and knockdown of Akt1 abrogated the TXL-induced suppression of miR-155. In conclusion, TXL inhibits the vascular inflammatory response and neointimal hyperplasia induced by carotid artery ligation in mice. Suppression of miR-155 expression mediated by Akt1 and blockade of the feedback loop between miR-155 and TNF-α are important pathways whereby TXL exerts its vasoprotective effects. PMID:24951754

  18. Neural cryptography with feedback

    NASA Astrophysics Data System (ADS)

    Ruttor, Andreas; Kinzel, Wolfgang; Shacham, Lanir; Kanter, Ido

    2004-04-01

    Neural cryptography is based on a competition between attractive and repulsive stochastic forces. A feedback mechanism is added to neural cryptography which increases the repulsive forces. Using numerical simulations and an analytic approach, the probability of a successful attack is calculated for different model parameters. Scaling laws are derived which show that feedback improves the security of the system. In addition, a network with feedback generates a pseudorandom bit sequence which can be used to encrypt and decrypt a secret message.

  19. Proteomic and metabolomic changes driven by elevating myocardial creatine suggest novel metabolic feedback mechanisms.

    PubMed

    Zervou, Sevasti; Yin, Xiaoke; Nabeebaccus, Adam A; O'Brien, Brett A; Cross, Rebecca L; McAndrew, Debra J; Atkinson, R Andrew; Eykyn, Thomas R; Mayr, Manuel; Neubauer, Stefan; Lygate, Craig A

    2016-08-01

    Mice over-expressing the creatine transporter have elevated myocardial creatine levels [Cr] and are protected against ischaemia/reperfusion injury via improved energy reserve. However, mice with very high [Cr] develop cardiac hypertrophy and dysfunction. To investigate these contrasting effects, we applied a non-biased hypothesis-generating approach to quantify global protein and metabolite changes in the LV of mice stratified for [Cr] levels: wildtype, moderately elevated, and high [Cr] (65-85; 100-135; 160-250 nmol/mg protein, respectively). Male mice received an echocardiogram at 7 weeks of age with tissue harvested at 8 weeks. RV was used for [Cr] quantification by HPLC to select LV tissue for subsequent analysis. Two-dimensional difference in-gel electrophoresis identified differentially expressed proteins, which were manually picked and trypsin digested for nano-LC-MS/MS. Principal component analysis (PCA) showed efficient group separation (ANOVA P ≤ 0.05) and peptide sequences were identified by mouse database (UniProt 201203) using Mascot. A total of 27 unique proteins were found to be differentially expressed between normal and high [Cr], with proteins showing [Cr]-dependent differential expression, chosen for confirmation, e.g. α-crystallin B, a heat shock protein implicated in cardio-protection and myozenin-2, which could contribute to the hypertrophic phenotype. Nuclear magnetic resonance (¹H-NMR at 700 MHz) identified multiple strong correlations between [Cr] and key cardiac metabolites. For example, positive correlations with α-glucose (r² = 0.45; P = 0.002), acetyl-carnitine (r² = 0.50; P = 0.001), glutamine (r² = 0.59; P = 0.0002); and negative correlations with taurine (r² = 0.74; P < 0.0001), fumarate (r² = 0.45; P = 0.003), aspartate (r² = 0.59; P = 0.0002), alanine (r² = 0.66; P < 0.0001) and phosphocholine (r² = 0.60; P = 0.0002). These findings suggest wide-ranging and hitherto unexpected

  20. STAT3 inhibition suppresses proliferation of retinoblastoma through down-regulation of positive feedback loop of STAT3/miR-17-92 clusters

    PubMed Central

    Jo, Dong Hyun; Kim, Jin Hyoung; Cho, Chang Sik; Cho, Young-Lai; Jun, Hyoung Oh; Yu, Young Suk; Min, Jeong-Ki; Kim, Jeong Hun

    2014-01-01

    Retinoblastoma, the most common intraocular malignant tumor in children, is characterized by the loss of both functional alleles of RB1 gene, which however alone cannot maintain malignant characteristics of retinoblastoma cells. Nevertheless, the investigation of other molecular aberrations such as matrix metalloproteinases (MMPs) and miRNAs is still lacking. In this study, we demonstrate that STAT3 is activated in retinoblastoma cells, Ki67-positive areas of in vivo orthotopic tumors in BALB/c nude mice, and human retinoblastoma tissues of the advanced stage. Furthermore, target genes of STAT3 including BCL2, BCL2L1, BIRC5, and MMP9 are up-regulated in retinoblastoma cells compared to other retinal constituent cells. Interestingly, STAT3 inhibition by targeted siRNA suppresses the proliferation of retinoblastoma cells and the formation of in vivo orthotopic tumors. In line with these results, STAT3 siRNA effectively induces down-regulation of target genes of STAT3. In addition, miRNA microarray analysis and further real-time PCR experiments with STAT3 siRNA treatment show that STAT3 activation is related to the up-regulation of miR-17-92 clusters in retinoblastoma cells via positive feedback loop between them. In conclusion, we suggest that STAT3 inhibition could be a potential therapeutic approach in retinoblastoma through the suppression of tumor proliferation. PMID:25359779

  1. STAT3 inhibition suppresses proliferation of retinoblastoma through down-regulation of positive feedback loop of STAT3/miR-17-92 clusters.

    PubMed

    Jo, Dong Hyun; Kim, Jin Hyoung; Cho, Chang Sik; Cho, Young-Lai; Jun, Hyoung Oh; Yu, Young Suk; Min, Jeong-Ki; Kim, Jeong Hun

    2014-11-30

    Retinoblastoma, the most common intraocular malignant tumor in children, is characterized by the loss of both functional alleles of RB1 gene, which however alone cannot maintain malignant characteristics of retinoblastoma cells. Nevertheless, the investigation of other molecular aberrations such as matrix metalloproteinases (MMPs) and miRNAs is still lacking. In this study, we demonstrate that STAT3 is activated in retinoblastoma cells, Ki67-positive areas of in vivo orthotopic tumors in BALB/c nude mice, and human retinoblastoma tissues of the advanced stage. Furthermore, target genes of STAT3 including BCL2, BCL2L1, BIRC5, and MMP9 are up-regulated in retinoblastoma cells compared to other retinal constituent cells. Interestingly, STAT3 inhibition by targeted siRNA suppresses the proliferation of retinoblastoma cells and the formation of in vivo orthotopic tumors. In line with these results, STAT3 siRNA effectively induces down-regulation of target genes of STAT3. In addition, miRNA microarray analysis and further real-time PCR experiments with STAT3 siRNA treatment show that STAT3 activation is related to the up-regulation of miR-17-92 clusters in retinoblastoma cells via positive feedback loop between them. In conclusion, we suggest that STAT3 inhibition could be a potential therapeutic approach in retinoblastoma through the suppression of tumor proliferation. PMID:25359779

  2. Parametric stability of continuous shafts, connected to mechanisms with position-dependent inertia

    NASA Astrophysics Data System (ADS)

    Turhan, O.; Koser, K.

    2004-10-01

    Stability of the parametrically excited torsional vibrations of shafts connected to mechanisms with position-dependent inertia is studied via a version of Bolotin's method. The shafts are considered to be torsionally elastic, distributed parameter systems and discretized through a finite element scheme. The mechanisms are modelled by a linearized Eksergian equation of motion. A general method of analysis is described and applied to examples with slider-crank and Scotch-yoke mechanisms.

  3. The Power of Feedback

    ERIC Educational Resources Information Center

    Hattie, John; Timperley, Helen

    2007-01-01

    Feedback is one of the most powerful influences on learning and achievement, but this impact can be either positive or negative. Its power is frequently mentioned in articles about learning and teaching, but surprisingly few recent studies have systematically investigated its meaning. This article provides a conceptual analysis of feedback and…

  4. SIRTF/IRS cryogenic grating drive mechanism (ARC second positioning at 4 K)

    NASA Technical Reports Server (NTRS)

    Kubitschek, Michael J.

    1991-01-01

    The requirements, design, and test results of a grating drive mechanism for the Infrared Spectrograph (IRS) science instrument on the proposed superfluid helium-cooled Space Infrared Telescope Facility (SIRTF) are described. The IRS grating drive mechanism, tested in the fall of 1989, satisfied all performance requirements in vacuum at 4 K. Measured mechanism performance included: 1.4 arc sec root-mean-square (rms) error positioning resolution; 2.2 arc sec rms position repeatability error, less than 10 millijoules/deg dissipated power; and 170 deg angular range of travel. Mechanisms that precisely position optical elements at very low cryogenic temperatures (at/below 4 K) are vital to the operating success of a number of proposed infrared scientific instruments like those in SIRTF.

  5. Calibration of positional consistency between mechanical shaft and electronic boresight for radar antenna

    NASA Astrophysics Data System (ADS)

    Jiang, Li; Wang, Dong-wei; Liu, Yong; Chen, Xiao-hui; Liu, Yue-dong

    2015-02-01

    By fixing a glass cubic prism facing an antenna, the positional relation between the coordinates of the cubic prism and the mechanical shaft was measured in a lab for the antenna, and the positional relation between the coordinates of the cubic prism and the wave was measured in a microwave anechoic chamber. The positional relation between the antenna and the wave was used to calibrate the positional consistency between the mechanical shaft and the electronic boresight. The calibration uncertainty was calibrated by analyzing the measurement data collected in the lab and the microwave anechoic chamber. Experimental results indicated that the proposed method could be used to calibrate the positional consistency between the antenna and the electronic boresight of a radar system, and the calibration results are within the accuracy limits for radar antennas.

  6. Newton-Wigner position operator and the corresponding spin operator in relativistic quantum mechanics

    NASA Astrophysics Data System (ADS)

    Choi, Taeseung

    2015-03-01

    A relativistic spin operator is the difference between the total and the orbital angular momentum. As the unique position operator for a localized state, the remarkable Newton-Wigner position operator, which has all the desirable commutation relations of a position operator, can give a proper spin operator. Historically, the three important spin operators proposed by Bogolubov et al., Pryce, and Foldy-Woutheysen, respectively were investigated to manifest a spin operator corresponding to the Newton-Wigner position operator. We clarify a unique spin operator in relativistic quantum mechanics, which can be described by using the Dirac Hamiltonian.

  7. Inhibitory and toxic effects of extracellular self-DNA in litter: a mechanism for negative plant-soil feedbacks?

    PubMed

    Mazzoleni, Stefano; Bonanomi, Giuliano; Incerti, Guido; Chiusano, Maria Luisa; Termolino, Pasquale; Mingo, Antonio; Senatore, Mauro; Giannino, Francesco; Cartenì, Fabrizio; Rietkerk, Max; Lanzotti, Virginia

    2015-02-01

    Plant-soil negative feedback (NF) is recognized as an important factor affecting plant communities. The objectives of this work were to assess the effects of litter phytotoxicity and autotoxicity on root proliferation, and to test the hypothesis that DNA is a driver of litter autotoxicity and plant-soil NF. The inhibitory effect of decomposed litter was studied in different bioassays. Litter biochemical changes were evaluated with nuclear magnetic resonance (NMR) spectroscopy. DNA accumulation in litter and soil was measured and DNA toxicity was assessed in laboratory experiments. Undecomposed litter caused nonspecific inhibition of root growth, while autotoxicity was produced by aged litter. The addition of activated carbon (AC) removed phytotoxicity, but was ineffective against autotoxicity. Phytotoxicity was related to known labile allelopathic compounds. Restricted (13) C NMR signals related to nucleic acids were the only ones negatively correlated with root growth on conspecific substrates. DNA accumulation was observed in both litter decomposition and soil history experiments. Extracted total DNA showed evident species-specific toxicity. Results indicate a general occurrence of litter autotoxicity related to the exposure to fragmented self-DNA. The evidence also suggests the involvement of accumulated extracellular DNA in plant-soil NF. Further studies are needed to further investigate this unexpected function of extracellular DNA at the ecosystem level and related cellular and molecular mechanisms. PMID:25354164

  8. Assessing the Importance of the Evaporation-Wind Feedback Mechanism in the Modulation of Simulated Madden-Julian Oscillations

    NASA Technical Reports Server (NTRS)

    Colon, Edward; Lindesay, James; Suarez, Max J.

    1998-01-01

    An examination of simulated Madden-Julian Oscillation (MJO) response to active and suppressed air-sea interactions is made using an aquaplanet model employing a realistic representation of the hydrologic cyle. In general, the evaporation-wind feedback (EWF) results from a coupling between tropical zonal surface wind stresses and evaporation anomalies. Recent observational and theoretical studies have questioned the significance of EWF in sustaining the predominantly wavenumber 1 eastward propagating mode commonly attributed to the interaction between large scale convergence and cumulus-scale convection (conditional instability of the second kind, CISK). To ascertain the nature of the EWF dependence on lower boundary conditions and thus quantify its effect on MJO development, a series of numerical experiments were conducted employing various zonally symmetric sea surface temperature (SST) distributions with active and suppressed EWF mechanisms. Results suggest that a correlation exists between tropical SSTs and the efficacy of the EWF in vertically redistributing heat acquired through surface wind stresses. It has been determined that the removal of the EWF is not a crucial factor in the dampening of the simulated MJO at high equatorial SSTs. The additional energy fed into the developing convective mode by the EWF selectively amplifies higher order wave modes in all numerical experiments thus boosting overall variances in oscillatory responses.

  9. Kinesin Kip2 enhances microtubule growth in vitro through length-dependent feedback on polymerization and catastrophe.

    PubMed

    Hibbel, Anneke; Bogdanova, Aliona; Mahamdeh, Mohammed; Jannasch, Anita; Storch, Marko; Schäffer, Erik; Liakopoulos, Dimitris; Howard, Jonathon

    2015-01-01

    The size and position of mitotic spindles is determined by the lengths of their constituent microtubules. Regulation of microtubule length requires feedback to set the balance between growth and shrinkage. Whereas negative feedback mechanisms for microtubule length control, based on depolymerizing kinesins and severing proteins, have been studied extensively, positive feedback mechanisms are not known. Here, we report that the budding yeast kinesin Kip2 is a microtubule polymerase and catastrophe inhibitor in vitro that uses its processive motor activity as part of a feedback loop to further promote microtubule growth. Positive feedback arises because longer microtubules bind more motors, which walk to the ends where they reinforce growth and inhibit catastrophe. We propose that positive feedback, common in biochemical pathways to switch between signaling states, can also be used in a mechanical signaling pathway to switch between structural states, in this case between short and long polymers. PMID:26576948

  10. Coevolution of topography, soils, and vegetation in upland landscapes: Using cinder cones to elucidate ecohydrogeomorphic feedback mechanisms

    NASA Astrophysics Data System (ADS)

    McGuire, L.; Pelletier, J. D.; Rasmussen, C.

    2013-12-01

    observed asymmetries in hillslope morphology are not present initially, but appear to develop over time as a result of differences in post-emplacement processes that may be attributed to aspect-induced microclimatic effects on long-term sediment transport rates. Results provide additional constraints on the timing and magnitude of feedback mechanisms among topography, biomass, and soil development as well as improve our understanding of cinder cone evolution within different climates.

  11. The CaM Kinase CMK-1 Mediates a Negative Feedback Mechanism Coupling the C. elegans Glutamate Receptor GLR-1 with Its Own Transcription

    PubMed Central

    Moss, Benjamin J.; Park, Lidia; Dahlberg, Caroline L.; Juo, Peter

    2016-01-01

    Regulation of synaptic AMPA receptor levels is a major mechanism underlying homeostatic synaptic scaling. While in vitro studies have implicated several molecules in synaptic scaling, the in vivo mechanisms linking chronic changes in synaptic activity to alterations in AMPA receptor expression are not well understood. Here we use a genetic approach in C. elegans to dissect a negative feedback pathway coupling levels of the AMPA receptor GLR-1 with its own transcription. GLR-1 trafficking mutants with decreased synaptic receptors in the ventral nerve cord (VNC) exhibit compensatory increases in glr-1 mRNA, which can be attributed to increased glr-1 transcription. Glutamatergic transmission mutants lacking presynaptic eat-4/VGLUT or postsynaptic glr-1, exhibit compensatory increases in glr-1 transcription, suggesting that loss of GLR-1 activity is sufficient to trigger the feedback pathway. Direct and specific inhibition of GLR-1-expressing neurons using a chemical genetic silencing approach also results in increased glr-1 transcription. Conversely, expression of a constitutively active version of GLR-1 results in decreased glr-1 transcription, suggesting that bidirectional changes in GLR-1 signaling results in reciprocal alterations in glr-1 transcription. We identify the CMK-1/CaMK signaling axis as a mediator of the glr-1 transcriptional feedback mechanism. Loss-of-function mutations in the upstream kinase ckk-1/CaMKK, the CaM kinase cmk-1/CaMK, or a downstream transcription factor crh-1/CREB, result in increased glr-1 transcription, suggesting that the CMK-1 signaling pathway functions to repress glr-1 transcription. Genetic double mutant analyses suggest that CMK-1 signaling is required for the glr-1 transcriptional feedback pathway. Furthermore, alterations in GLR-1 signaling that trigger the feedback mechanism also regulate the nucleocytoplasmic distribution of CMK-1, and activated, nuclear-localized CMK-1 blocks the feedback pathway. We propose a model in

  12. Nonlinear feedback control of multiple robot arms

    NASA Technical Reports Server (NTRS)

    Tarn, T. J.; Yun, X.; Bejczy, A. K.

    1987-01-01

    Multiple coordinated robot arms are modeled by considering the arms: (1) as closed kinematic chains, and (2) as a force constrained mechanical system working on the same object simultaneously. In both formulations a new dynamic control method is discussed. It is based on a feedback linearization and simultaneous output decoupling technique. Applying a nonlinear feedback and a nonlinear coordinate transformation, the complicated model of the multiple robot arms in either formulation is converted into a linear and output decoupled system. The linear system control theory and optimal control theory are used to design robust controllers in the task space. The first formulation has the advantage of automatically handling the coordination and load distribution among the robot arms. In the second formulation, by choosing a general output equation, researchers can superimpose the position and velocity error feedback with the force-torque error feedback in the task space simultaneously.

  13. Effects of pneumoperitoneal pressure and position changes on respiratory mechanics during laparoscopic colectomy

    PubMed Central

    Park, Jin Suk; Ahn, Eun Jin; Ko, Duk Dong; Shin, Hwa Yong; Baek, Chong Hwa; Jung, Yong Hun; Woo, Young Cheol; Kim, Jin Yun; Koo, Gill Hoi

    2012-01-01

    Background This study was designed to assess the effects of pneumoperitoneal pressure (PP) and positional changes on the respiratory mechanics during laparoscopy assisted colectomy. Methods Peak inspiratory pressure, plateau pressure, lung compliance, and airway resistance were recorded in PP of 10 mmHg and 15 mmHg, with the position change in 5 steps: head-down at 20°, head-down at 10°, neutral position, head-up at 10° and head-up at 20°. Results When the patient was placed head-down, the position change accentuated the effects of pneumoperitoneum on respiratory mechanics. However, when the patient was placed in a head-up position during pneumoperitoneum the results showed no pattern. In the 20° head-up position with the PP being 10 mmHg, the compliance increased from 30.6 to 32.6 ml/cmH2O compared with neutral position (P = 0.002). However with the PP being 15 mmHg, the compliance had not changed compared with neutral position (P = 0.989). In 20° head-down position with the PP of 10 mmHg, the compliance was measured as 24.2 ml/cmH2O. This was higher than that for patients in the 10° head-down position with a PP of 15 mmHg, which was recorded as 21.2 ml/cmH2O. Also in the airway resistance, the patient in the 20° head-down position with the PP of 10 mmHg showed 15.8 cmH2O/L/sec, while the patient in the 10° head-down position with the PP of 15 mmHg showed 16.2 cmH2O/L/sec of airway resistance. These results were not statistically significant but still suggested that the head-down position accentuated the effects of pneumoperitoneum on respiratory mechanics. Conclusions Our results suggest that respiratory mechanics are affected by the patient position and the level of PP - the latter having greater effect. PMID:23198035

  14. MiR218 Modulates Wnt Signaling in Mouse Cardiac Stem Cells by Promoting Proliferation and Inhibiting Differentiation through a Positive Feedback Loop

    PubMed Central

    Wang, Yongshun; Liu, Jingjin; Cui, Jinjin; Sun, Meng; Du, Wenjuan; Chen, Tao; Ming, Xing; Zhang, Lulu; Tian, Jiangtian; Li, Ji; Yin, Li; Liu, Fang; Pu, Zhongyue; Lv, Bo; Hou, Jingbo; Yu, Bo

    2016-01-01

    MiRNA expression was determined in both proliferating and differentiated cardiac stem cells (CSCs) through a comprehensive miRNA microarray analysis. We selected miR218 for functional follow-up studies to examine its significance in CSCs. First, we observed that the expression of miR218 was altered in CSCs during differentiation into cardiomyocytes, and transfection of an miR218 mimic or miR218 inhibitor affected the myocardial differentiation of CSCs. Furthermore, we observed that a negative regulator of Wnt signaling, sFRP2, was a direct target of miR218, and the protein levels of sFRP2 were increased in cells transfected with the synthetic miR218 inhibitor. In contrast, transfection with the miR218 mimic decreased the expression of sFRP2 and potentiated Wnt signaling. The subsequent down-regulation of sFRP2 by shRNA potentiated Wnt signaling, contributing to a gene expression program that is important for CSC proliferation and cardiac differentiation. Specifically, canonical Wnt signaling induced miR218 transcription. Thus, miR218 and Wnt signaling were coupled through a feed-forward positive feedback loop, forming a biological regulatory circuit. Together, these results provide the first evidence that miR218 plays an important role in CSC proliferation and differentiation through the canonical Wnt signaling pathway. PMID:26860887

  15. CXCL3 contributes to CD133+ CSCs maintenance and forms a positive feedback regulation loop with CD133 in HCC via Erk1/2 phosphorylation

    PubMed Central

    Zhang, Lin; Zhang, Lixing; Li, Hong; Ge, Chao; Zhao, Fangyu; Tian, Hua; Chen, Taoyang; Jiang, Guoping; Xie, Haiyang; Cui, Ying; Yao, Ming; Li, Jinjun

    2016-01-01

    Although the chemotactic cytokine CXCL3 is thought to play an important role in tumor initiation and invasion, little is known about its function in hepatocellular carcinoma (HCC). In our previous study, we found that Ikaros inhibited CD133 expression via the MAPK pathway in HCC. Here, we showed that Ikaros may indirectly down-regulate CXCL3 expression in HCC cells, which leads to better outcomes in patients with CD133+ cancer stem cell (CSC) populations. CD133 overexpression induced CXCL3 expression, and silencing of CD133 down-regulated CXCL3 in HCC cells. Knockdown of CXCL3 inhibited CD133+ HCC CSCs’ self-renewal and tumorigenesis. The serum CXCL3 level was higher in HCC patients’ samples than that in healthy individual. HCC patients with higher CXCL3 expression displayed a poor prognosis, and a high level of CXCL3 was significantly associated with vascular invasion and tumor capsule formation. Exogenous CXCL3 induced Erk1/2 and ETS1 phosphorylation and promoted CD133 expression, indicating a positive feedback loop between CXCL3 and CD133 gene expression in HCC cells via Erk1/2 activation. Together, our findings indicated that CXCL3 might be a potent therapeutic target for HCC. PMID:27255419

  16. In the Blink of an Eye: Relating Positive-Feedback Sensitivity to Striatal Dopamine D2-Like Receptors through Blink Rate

    PubMed Central

    Groman, Stephanie M.; James, Alex S.; Seu, Emanuele; Tran, Steven; Clark, Taylor A.; Harpster, Sandra N.; Crawford, Maverick; Burtner, Joanna Lee; Feiler, Karen; Roth, Robert H.; Elsworth, John D.; London, Edythe D.

    2014-01-01

    For >30 years, positron emission tomography (PET) has proven to be a powerful approach for measuring aspects of dopaminergic transmission in the living human brain; this technique has revealed important relationships between dopamine D2-like receptors and dimensions of normal behavior, such as human impulsivity, and psychopathology, particularly behavioral addictions. Nevertheless, PET is an indirect estimate that lacks cellular and functional resolution and, in some cases, is not entirely pharmacologically specific. To identify the relationships between PET estimates of D2-like receptor availability and direct in vitro measures of receptor number, affinity, and function, we conducted neuroimaging and behavioral and molecular pharmacological assessments in a group of adult male vervet monkeys. Data gathered from these studies indicate that variation in D2-like receptor PET measurements is related to reversal-learning performance and sensitivity to positive feedback and is associated with in vitro estimates of the density of functional dopamine D2-like receptors. Furthermore, we report that a simple behavioral measure, eyeblink rate, reveals novel and crucial links between neuroimaging assessments and in vitro measures of dopamine D2 receptors. PMID:25339755

  17. HD-Zip Proteins GL2 and HDG11 Have Redundant Functions in Arabidopsis Trichomes, and GL2 Activates a Positive Feedback Loop via MYB23[W

    PubMed Central

    Khosla, Aashima; Paper, Janet M.; Boehler, Allison P.; Bradley, Amanda M.; Neumann, Titus R.; Schrick, Kathrin

    2014-01-01

    The class IV homeodomain leucine zipper transcription factor GLABRA2 (GL2) acts in a complex regulatory circuit that regulates the differentiation of trichomes in Arabidopsis thaliana. We describe a genetic interaction with HOMEODOMAIN GLABROUS11 (HDG11), previously identified as a negative regulator of trichome branching. gl2 hdg11 double mutants display enhanced trichome cell-type differentiation defects. Transgenic expression of HDG11 using the GL2 promoter partially suppresses gl2 trichome phenotypes. Vice versa, expression of GL2 under the control of its native promoter partially complements hdg11 ectopic branching. Since gl2 hdg11 and gl2 myb23 double mutants and the triple mutant display similar trichome differentiation defects, we investigated a connection to the R2R3-MYB transcription factor MYB23. We show that MYB23 transcript levels are significantly reduced in shoots from gl2 mutants and that GL2 can drive the expression of a MYB23-promoter fusion to green fluorescent protein. Yeast one-hybrid, chromatin immunoprecipitation, and in planta reporter gene experiments indicate that an L1-box in the MYB23 promoter acts as a GL2 binding site. Taken together, our findings reveal a functional redundancy between GL2 and HDG11, two homeodomain leucine zipper transcription factors previously thought to mediate opposing functions in trichome morphogenesis. A model is proposed in which GL2 transcript levels are maintained through a positive feedback loop involving GL2 activation of MYB23. PMID:24824485

  18. Short-term retention effect of rehabilitation using head position-based electrotactile feedback to the tongue: influence of vestibular loss and old-age.

    PubMed

    Ghulyan-Bedikian, Vénéra; Paolino, Michel; Paolino, Fabien

    2013-09-01

    Our objective was to evaluate whether the severity of vestibular loss and old-age (>65) affect a patient's ability to benefit from training using head-position based, tongue-placed electrotactile feedback. Seventy-one chronic dizzy patients, who had reached a plateau with their conventional rehabilitation, followed six 1-h training sessions during 4 consecutive days (once on days 1 and 4, twice on days 2 and 3). They presented bilateral vestibular areflexia (BVA), bilateral vestibular losses (BVL), unilateral vestibular areflexia or unilateral vestibular losses and were divided into two age-subgroups (≤65 and >65). Posturographic assessments were performed without the device, 4h before and after the training. Patients were tested with eyes opened and eyes closed (EC) on static and dynamic (passively tilting) platforms. The studied posturographic scores improved significantly, especially under test conditions restricting either visual or somatosensory input. This 4-h retention effect was greater in older compared to younger patients and was proportional to the degree of vestibular loss, patients with increased vestibular losses showing greater improvements. In bilateral patients, who constantly fell under dynamic-EC condition at the baseline, the therapy effect was expressed by disappearance of falls in BVL and significant prolongation in time-to-fall in BVA subgroups. Globally, our data showed that short training with head-position based, tongue-placed electrotactile biofeedback improves balance in chronic vestibulopathic patients some 16.74% beyond that achieved with standard balance physiotherapy. Further studies with longer use of this biofeedback are needed to investigate whether this approach could have long-lasting retention effect on balance and quality of life. PMID:23623605

  19. Cross-Species Antiviral Activity of Goose Interferons against Duck Plague Virus Is Related to Its Positive Self-Feedback Regulation and Subsequent Interferon Stimulated Genes Induction

    PubMed Central

    Zhou, Hao; Chen, Shun; Zhou, Qin; Wei, Yunan; Wang, Mingshu; Jia, Renyong; Zhu, Dekang; Liu, Mafeng; Liu, Fei; Yang, Qiao; Wu, Ying; Sun, Kunfeng; Chen, Xiaoyue; Cheng, Anchun

    2016-01-01

    Interferons are a group of antiviral cytokines acting as the first line of defense in the antiviral immunity. Here, we describe the antiviral activity of goose type I interferon (IFNα) and type II interferon (IFNγ) against duck plague virus (DPV). Recombinant goose IFNα and IFNγ proteins of approximately 20 kDa and 18 kDa, respectively, were expressed. Following DPV-enhanced green fluorescent protein (EGFP) infection of duck embryo fibroblast cells (DEFs) with IFNα and IFNγ pre-treatment, the number of viral gene copies decreased more than 100-fold, with viral titers dropping approximately 100-fold. Compared to the control, DPV-EGFP cell positivity was decreased by goose IFNα and IFNγ at 36 hpi (3.89%; 0.79%) and 48 hpi (17.05%; 5.58%). In accordance with interferon-stimulated genes being the “workhorse” of IFN activity, the expression of duck myxovirus resistance (Mx) and oligoadenylate synthetases-like (OASL) was significantly upregulated (p < 0.001) by IFN treatment for 24 h. Interestingly, duck cells and goose cells showed a similar trend of increased ISG expression after goose IFNα and IFNγ pretreatment. Another interesting observation is that the positive feedback regulation of type I IFN and type II IFN by goose IFNα and IFNγ was confirmed in waterfowl for the first time. These results suggest that the antiviral activities of goose IFNα and IFNγ can likely be attributed to the potency with which downstream genes are induced by interferon. These findings will contribute to our understanding of the functional significance of the interferon antiviral system in aquatic birds and to the development of interferon-based prophylactic and therapeutic approaches against viral disease. PMID:27438848

  20. Cross-Species Antiviral Activity of Goose Interferons against Duck Plague Virus Is Related to Its Positive Self-Feedback Regulation and Subsequent Interferon Stimulated Genes Induction.

    PubMed

    Zhou, Hao; Chen, Shun; Zhou, Qin; Wei, Yunan; Wang, Mingshu; Jia, Renyong; Zhu, Dekang; Liu, Mafeng; Liu, Fei; Yang, Qiao; Wu, Ying; Sun, Kunfeng; Chen, Xiaoyue; Cheng, Anchun

    2016-01-01

    Interferons are a group of antiviral cytokines acting as the first line of defense in the antiviral immunity. Here, we describe the antiviral activity of goose type I interferon (IFNα) and type II interferon (IFNγ) against duck plague virus (DPV). Recombinant goose IFNα and IFNγ proteins of approximately 20 kDa and 18 kDa, respectively, were expressed. Following DPV-enhanced green fluorescent protein (EGFP) infection of duck embryo fibroblast cells (DEFs) with IFNα and IFNγ pre-treatment, the number of viral gene copies decreased more than 100-fold, with viral titers dropping approximately 100-fold. Compared to the control, DPV-EGFP cell positivity was decreased by goose IFNα and IFNγ at 36 hpi (3.89%; 0.79%) and 48 hpi (17.05%; 5.58%). In accordance with interferon-stimulated genes being the "workhorse" of IFN activity, the expression of duck myxovirus resistance (Mx) and oligoadenylate synthetases-like (OASL) was significantly upregulated (p < 0.001) by IFN treatment for 24 h. Interestingly, duck cells and goose cells showed a similar trend of increased ISG expression after goose IFNα and IFNγ pretreatment. Another interesting observation is that the positive feedback regulation of type I IFN and type II IFN by goose IFNα and IFNγ was confirmed in waterfowl for the first time. These results suggest that the antiviral activities of goose IFNα and IFNγ can likely be attributed to the potency with which downstream genes are induced by interferon. These findings will contribute to our understanding of the functional significance of the interferon antiviral system in aquatic birds and to the development of interferon-based prophylactic and therapeutic approaches against viral disease. PMID:27438848

  1. Increasing Induction-Level Teachers' Positive-to-Negative Communication Ratio and Use of Behavior-Specific Praise through E-Mailed Performance Feedback and Its Effect on Students' Task Engagement

    ERIC Educational Resources Information Center

    Rathel, Jeanna M.; Drasgow, Erik; Brown, William H.; Marshall, Kathleen J.

    2014-01-01

    The purpose of this study was to examine the effects of e-mailed specific performance feedback that included progress monitoring graphs on induction-level teachers' ratios of positive-to-negative communication behaviors and their use of behavior-specific praise in classrooms for students with emotional and behavioral disorders, mild…

  2. Obg-like ATPase 1 regulates global protein serine/threonine phosphorylation in cancer cells by suppressing the GSK3β-inhibitor 2-PP1 positive feedback loop

    PubMed Central

    Xu, Dong; Song, Renduo; Wang, Guohui; Jeyabal, Prince V.S.; Weiskoff, Amanda M.; Ding, Kefeng; Shi, Zheng-Zheng

    2016-01-01

    OLA1 is an Obg family P-loop NTPase that possesses both GTP- and ATP-hydrolyzing activities. Here we report that OLA1 is a GSK3β interacting protein, and through its ATPase activity, inhibits the GSK3β-mediated activation of protein serine/threonine phosphatase 1 (PP1). It is hypothesized that GSK3β phosphorylates inhibitor 2 (I-2) of PP1 at Thr-72 and activates the PP1 · I-2 complex, which in turn dephosphorylates and stimulates GSK3β, thus forming a positive feedback loop. We revealed that the positive feedback loop is normally suppressed by OLA1, and becomes over-activated under OLA1 deficiency, resulting in increased cellular PP1 activity and dephosphorylation of multiple Ser/Thr phosphoproteins, and more strikingly, decreased global protein threonine phosphorylation. Furthermore, using xenograft models of colon cancer (H116) and ovarian cancer (SKOV3), we established a correlation among downregulation of OLA1, over-activation of the positive feedback loop as indicated by under-phosphorylation of I-2, and more aggressive tumor growth. This study provides the first evidence for the existence of a GSK3β-I-2-PP1 positive feedback loop in human cancer cells, and identifies OLA1 as an endogenous suppressor of this signaling motif. PMID:26655089

  3. Wide range force feedback for catheter insertion mechanism for use in minimally invasive mitral valve repair surgery

    NASA Astrophysics Data System (ADS)

    Ahmadi, Roozbeh; Sokhanvar, Saeed; Packirisamy, Muthukumaran; Dargahi, Javad

    2009-02-01

    Mitral valve regurgitation (MR) is a condition in which heart's mitral valve does not close tightly, which allows blood to leak back into the left atrium. Restoring the dimension of the mitral-valve annulus by percutaneous intervention surgery is a common choice to treat MR. Currently, this kind of open heart annuloplasty surgery is being performed through sternotomy with cardiomyopathy bypass. In order to reduce trauma to the patient and also to eliminate bypass surgery, robotic assisted minimally invasive surgery (MIS) procedure, which requires small keyhole incisions, has a great potential. To perform this surgery through MIS procedure, an accurate computer controlled catheter with wide-range force feedback capabilities is required. There are three types of tissues at the site of operation: mitral leaflet, mitral annulus and left atrium. The maximum allowable applied force to these three types of tissue is totally different. For instance, leaflet tissue is the most sensitive one with the lowest allowable force capacity. For this application, therefore, a wide-range force sensing is highly required. Most of the sensors that have been developed for use in MIS applications have a limited range of sensing. Therefore, they need to be calibrated for different types of tissue. The present work, reports on the design, modeling and simulation of a novel wide-range optical force sensor for measurement of contact pressure between catheter tip and heart tissue. The proposed sensor offers a wide input range with a high resolution and sensitivity over this range. Using Micro-Electro-Mechanical-Systems (MEMS) technology, this sensor can be microfabricated and integrated with commercially available catheters.

  4. Feedback has a positive effect on cognitive function during total sleep deprivation if there is sufficient time for it to be effectively processed.

    PubMed

    Roach, Gregory D; Lamond, Nicole; Dawson, Drew

    2016-01-01

    This study examined whether the provision of feedback and the interval between successive stimuli interact to affect performance on a serial simple reaction time test during sleep deprivation. Sixteen participants (9 female, 7 male, aged 18-27 yr) completed four versions of the 5-min psychomotor vigilance task for a handheld personal digital assistant (PalmPVT) every 2 h during 28 h of sustained wakefulness. The four versions differed in terms of whether or not they provided feedback immediately after each response, and whether the inter-stimulus intervals (ISIs) were long (2-10 s) or short (1-5 s). Cognitive function was assessed using reciprocal response time and percentage of responses that were lapses (i.e., had a response time ≥ 500 ms). Data were analysed using repeated measures ANOVA with three within-subjects factors: test session, feedback, and ISI. For both measures, the only significant interaction was between feedback and ISI. Cognitive function was enhanced by feedback when the ISIs were long because it provided motivation. Cognitive function was not affected by feedback when the ISIs were short because there was insufficient time to both attend to the feedback and prepare for the subsequent stimulus. PMID:26360220

  5. Development of a tilt-positioning mechanism driven by flextensional piezoelectric actuators.

    PubMed

    Jing, Zijian; Xu, Minglong; Wu, Tonghui; Tian, Zheng

    2016-08-01

    Tilt-positioning mechanisms are required in optical systems for diverse applications. Compared to electromagnetic tilt-positioning mechanisms, piezoelectric tilters are superior with regard to high positioning resolution, cost-effectiveness, and no electromagnetic interference issues. But their applications are limited by small motion ranges. To overcome this problem, a novel piezoelectric tilt-positioning mechanism is proposed and developed in this paper, aiming to achieve a large output range in compact size. Serving this purpose, flextensional piezoelectric actuators (FPAs) are employed in this mechanism and their optimal structure is pursued. The existing approach to model and analyze the structure of FPAs is not perfect, making it challenging to exactly characterize and optimize actuator performance for its applications. To address this problem, a hybrid-body model of the FPAs is developed and based on this model, a governing equation is established to exactly and comprehensively characterize their kinematic performance. This equation allows the application requirement to be readily related to the actuator design, enabling the optimization of tilter design and the actuators. Using the optimized parameters, an experimental prototype is fabricated. This specimen achieved more than 15 mrad of angular travel at a small size of 35 × 42 × 42 mm, and the error between the analytical model and the experiment was less than 5%. These results support the accuracy of the hybrid-body model and indicate that the proposed tilter is very promising for practical applications. PMID:27587152

  6. A Positive Feedback Loop between Glial Cells Missing 1 and Human Chorionic Gonadotropin (hCG) Regulates Placental hCGβ Expression and Cell Differentiation

    PubMed Central

    Cheong, Mei-Leng; Wang, Liang-Jie; Chuang, Pei-Yun; Chang, Ching-Wen; Lee, Yun-Shien; Lo, Hsiao-Fan; Tsai, Ming-Song

    2015-01-01

    Human chorionic gonadotropin (hCG) is composed of a common α subunit and a placenta-specific β subunit. Importantly, hCG is highly expressed in the differentiated and multinucleated syncytiotrophoblast, which is formed via trophoblast cell fusion and stimulated by cyclic AMP (cAMP). Although the ubiquitous activating protein 2 (AP2) transcription factors TFAP2A and TFAP2C may regulate hCGβ expression, it remains unclear how cAMP stimulates placenta-specific hCGβ gene expression and trophoblastic differentiation. Here we demonstrated that the placental transcription factor glial cells missing 1 (GCM1) binds to a highly conserved promoter region in all six hCGβ paralogues by chromatin immunoprecipitation-on-chip (ChIP-chip) analyses. We further showed that cAMP stimulates GCM1 and the CBP coactivator to activate the hCGβ promoter through a GCM1-binding site (GBS1), which also constitutes a previously identified AP2 site. Given that TFAP2C may compete with GCM1 for GBS1, cAMP enhances the association between the hCGβ promoter and GCM1 but not TFAP2C. Indeed, the hCG-cAMP-protein kinase A (PKA) signaling pathway also stimulates Ser269 and Ser275 phosphorylation of GCM1, which recruits CBP to mediate GCM1 acetylation and stabilization. Consequently, hCG stimulates the expression of GCM1 target genes, including the fusogenic protein syncytin-1, to promote placental cell fusion. Our study reveals a positive feedback loop between GCM1 and hCG regulating placental hCGβ expression and cell differentiation. PMID:26503785

  7. The prostaglandin E2 receptor EP4 is integral to a positive feedback loop for prostaglandin E2 production in human macrophages infected with Mycobacterium tuberculosis

    PubMed Central

    Nishimura, Tomoyasu; Zhao, Xiaomin; Gan, Huixian; Koyasu, Shigeo; Remold, Heinz G.

    2013-01-01

    Prostaglandin E2 (PGE2) is an important biological mediator involved in the defense against Mycobacterium tuberculosis (Mtb) infection. Previously, we reported that in macrophages (Mφs), infection with avirulent Mtb H37Ra resulted in inhibition of necrosis by an inhibitory effect on mitochondrial permeability transition via the PGE2 receptor EP2. However, human Mφs also express EP4, a PGE2 receptor functionally closely related to EP2 that also couples to stimulatory guanine nucleotide binding protein, but the functional differences between EP2 and EP4 in Mtb-infected Mφs have been unclear. EP4 antagonist addition to H37Ra-infected Mφs inhibited the expression of cyclooxygenase 2 (COX2) and microsomal prostaglandin E synthase-1 (mPGES-1), which are involved in PGE2 production. Moreover, H37Ra infection induced PGE2 production through the Toll-like receptor (TLR) 2/p38 mitogen-activated protein kinase (MAPK) signaling pathway. Induction of COX2 and mPGES-1 expression by TLR2 stimulation or Mtb infection was increased after additional stimulation with EP4 agonist. Hence, in Mtb-infected Mφs, PGE2 production induced by pathogen recognition receptors/p38 MAPK signaling is up-regulated by EP4-triggered signaling to maintain an effective PGE2 concentration.—Nishimura, T., Zhao, X., Gan, H., Koyasu, S., and Remold, H. G. The prostaglandin E2 receptor EP4 is integral to a positive feedback loop for prostaglandin E2 production in human macrophages infected with Mycobacterium tuberculosis. PMID:23759445

  8. Bone Morphogenic Protein (BMP) Signaling Up-regulates Neutral Sphingomyelinase 2 to Suppress Chondrocyte Maturation via the Akt Protein Signaling Pathway as a Negative Feedback Mechanism*

    PubMed Central

    Kakoi, Hironori; Maeda, Shingo; Shinohara, Naohiro; Matsuyama, Kanehiro; Imamura, Katsuyuki; Kawamura, Ichiro; Nagano, Satoshi; Setoguchi, Takao; Yokouchi, Masahiro; Ishidou, Yasuhiro; Komiya, Setsuro

    2014-01-01

    Although bone morphogenic protein (BMP) signaling promotes chondrogenesis, it is not clear whether BMP-induced chondrocyte maturation is cell-autonomously terminated. Loss of function of Smpd3 in mice results in an increase in mature hypertrophic chondrocytes. Here, we report that in chondrocytes the Runx2-dependent expression of Smpd3 was increased by BMP-2 stimulation. Neutral sphingomyelinase 2 (nSMase2), encoded by the Smpd3 gene, was detected both in prehypertrophic and hypertrophic chondrocytes of mouse embryo bone cartilage. An siRNA for Smpd3, as well as the nSMase inhibitor GW4869, significantly enhanced BMP-2-induced differentiation and maturation of chondrocytes. Conversely, overexpression of Smpd3 or C2-ceramide, which mimics the function of nSMase2, inhibited chondrogenesis. Upon induction of Smpd3 siRNA or GW4869, phosphorylation of both Akt and S6 proteins was increased. The accelerated chondrogenesis induced by Smpd3 silencing was negated by application of the Akt inhibitor MK2206 or the mammalian target of rapamycin inhibitor rapamycin. Importantly, in mouse bone culture, GW4869 treatment significantly promoted BMP-2-induced hypertrophic maturation and calcification of chondrocytes, which subsequently was eliminated by C2-ceramide. Smpd3 knockdown decreased the apoptosis of terminally matured ATDC5 chondrocytes, probably as a result of decreased ceramide production. In addition, we found that expression of hyaluronan synthase 2 (Has2) was elevated by a loss of Smpd3, which was restored by MK2206. Indeed, expression of Has2 protein decreased in nSMase2-positive hypertrophic chondrocytes in the bones of mouse embryos. Our data suggest that the Smpd3/nSMase2-ceramide-Akt signaling axis negatively regulates BMP-induced chondrocyte maturation and Has2 expression to control the rate of endochondral ossification as a negative feedback mechanism. PMID:24505141

  9. Feedbacks in human-landscape systems

    NASA Astrophysics Data System (ADS)

    Chin, Anne

    2015-04-01

    As human interactions with Earth systems intensify in the "Anthropocene", understanding the complex relationships among human activity, landscape change, and societal responses to those changes is increasingly important. Interdisciplinary research centered on the theme of "feedbacks" in human-landscape systems serves as a promising focus for unraveling these interactions. Deciphering interacting human-landscape feedbacks extends our traditional approach of considering humans as unidirectional drivers of change. Enormous challenges exist, however, in quantifying impact-feedback loops in landscapes with significant human alterations. This paper illustrates an example of human-landscape interactions following a wildfire in Colorado (USA) that elicited feedback responses. After the 2012 Waldo Canyon Fire, concerns for heightened flood potential and debris flows associated with post-fire hydrologic changes prompted local landowners to construct tall fences at the base of a burned watershed. These actions changed the sediment transport regime and promoted further landscape change and human responses in a positive feedback cycle. The interactions ultimately increase flood and sediment hazards, rather than dampening the effects of fire. A simple agent-based model, capable of integrating social and hydro-geomorphological data, demonstrates how such interacting impacts and feedbacks could be simulated. Challenges for fully capturing human-landscape feedback interactions include the identification of diffuse and subtle feedbacks at a range of scales, the availability of data linking impact with response, the identification of multiple thresholds that trigger feedback mechanisms, and the varied metrics and data needed to represent both the physical and human systems. By collaborating with social scientists with expertise in the human causes of landscape change, as well as the human responses to those changes, geoscientists could more fully recognize and anticipate the coupled

  10. Simultaneous optimization of actuator position and control parameter for adaptive mechanical structures

    NASA Astrophysics Data System (ADS)

    Weber, Christian-Toralf; Gabbert, Ulrich; Enzmann, Marc R.

    1998-07-01

    The design of adaptive mechanical structures is divided into three parts: the structural design, the controller design and the placement of actuators and sensors. The objective of the design is to create a mechanical structure, which corresponds with the physical and technical requirements. The controller design includes the definition of the optimal controller law and the parameters required to create an actuator adjustment from the perceptible signals of the structural answer. The placement of the actuators and of the sensors give an answer to the question about the optimal distribution of the actuators and sensors in the structure. The sensor placement determines which signals are available to the automatic controller. The position of the actuators in the mechanical structure determines at which points control forces may act to influence the structural behavior in a suitable manner. The determination of the optimal position of the actuators require information about the controller design, the sensor position and the layout and the behavior of the structure. Based on the ideas of the shape optimization and topology optimization, a procedure will be presented, to handle simultaneously the discrete positions of the actuators and the continuous parameters of the controller. The method is based on an augmented Lagrangian function to include additional conditions and the discontinuity of the discrete variables into the objective function. The method will be demonstrated by an test example.

  11. Cytoplasmic flows as signatures for the mechanics of mitotic spindle positioning

    NASA Astrophysics Data System (ADS)

    Nazockdast, Ehssan; Rahimian, Abtin; Needleman, Daniel; Shelley, Michael

    2015-11-01

    The proper positioning of the mitotic spindle is crucial for asymmetric cell division and generating cell diversity during development. We use dynamic simulations to study the cytoplasmic flows generated by three possible active forcing mechanisms involved in positioning of the mitotic spindle in the first cell division of C.elegans embryo namely cortical pulling, cortical pushing, and cytoplasmic pulling mechanisms. The numerical platform we have developed for simulating cytoskeletal assemblies is the first to incorporate the interactions between the fibers and other intracellular bodies with the cytoplasmic fluid, while also accounting for their polymerization, and interactions with motor proteins. The hydrodynamic interactions are computed using boundary integral methods in Stokes flow coupled with highly efficient fast summation techniques that reduce the computational cost to scale linearly with the number of fibers and other bodies. We show that although all three force transduction mechanisms predict proper positioning and orientation of the mitotic spindle, each model produces a different signature in its induced cytoplasmic flow and MT conformation. We suggest that cytoplasmic flows and MT conformation can be used to differentiate between these mechanisms.

  12. Positive feedback between strain localization and fluid flow at the ductile-brittle transition leading to Pb-Zn-Fe-Cu-Ag ore deposits in Lavrion (Greece)

    NASA Astrophysics Data System (ADS)

    Scheffer, Christophe; Tarantola, Alexandre; Vanderhaeghe, Olivier

    2016-04-01

    fluid-rock interactions including organic matter present in the whole-rock during ore precipitation. These features show the positive feedback between localization of ductile-brittle deformation-recrystallization, fluid circulation and ore deposition. Accordingly, during orogenic gravitational collapse, the activation of mylonitic-cataclastic low-angle detachments, controlled at first order by temperature, are, at second order, influenced by lithologic heterogeneities that are determinant at localizing fluid circulation, allowing thus a multi-localization of the DBT and ore deposition.

  13. GTP cyclohydrolase I inhibition by the prototypic inhibitor 2, 4-diamino-6-hydroxypyrimidine. Mechanisms and unanticipated role of GTP cyclohydrolase I feedback regulatory protein.

    PubMed

    Xie, L; Smith, J A; Gross, S S

    1998-08-14

    2,4-Diamino-6-hydroxypyrimidine (DAHP) is considered to be a selective and direct-acting inhibitor of GTP cyclohydrolase I (GTPCH), the first and rate-limiting enzyme in the pathway for synthesis of tetrahydrobiopterin (BH4). Accordingly, DAHP has been widely employed to distinguish whether de novo BH4 synthesis is required in a given biological system. Although it has been assumed that DAHP inhibits GTPCH by direct competition with substrate GTP, this has never been formally demonstrated. In view of apparent structural homology between DAHP and BH4, we questioned whether DAHP may mimic BH4 in its inhibition of GTPCH by an indirect mechanism, involving interaction with a recently cloned 9.5-kDa protein termed GTPCH Feedback Regulatory Protein (GFRP). We show by reverse transcription-polymerase chain reaction that GFRP mRNA is constitutively expressed in rat aortic smooth muscle cells and further induced by treatment with immunostimulants. Moreover, functional GFRP is expressed and immunostimulant-induced BH4 accumulates in sufficient quantity to trigger feedback inhibition of GTPCH. Studies with DAHP reveal that GFRP is also essential to achieve potent inhibition of GTPCH. Indeed, DAHP inhibits GTPCH by dual mechanisms. At a relatively low concentration, DAHP emulates BH4 and engages the GFRP-dependent feedback inhibitory system; at higher concentrations, DAHP competes directly for binding with GTP substrate. This knowledge predicts that DAHP would preferably target GTPCH in tissues with abundant GFRP. PMID:9694862

  14. Toward Understanding the Catalytic Mechanism of Human Paraoxonase 1: Site-Specific Mutagenesis at Position 192

    PubMed Central

    Aggarwal, Geetika; Prajapati, Rameshwar; Tripathy, Rajan K.; Bajaj, Priyanka; Iyengar, A. R. Satvik; Sangamwar, Abhay T.; Pande, Abhay H.

    2016-01-01

    Human paraoxonase 1 (h-PON1) is a serum enzyme that can hydrolyze a variety of substrates. The enzyme exhibits anti-inflammatory, anti-oxidative, anti-atherogenic, anti-diabetic, anti-microbial and organophosphate-hydrolyzing activities. Thus, h-PON1 is a strong candidate for the development of therapeutic intervention against a variety conditions in human. However, the crystal structure of h-PON1 is not solved and the molecular details of how the enzyme hydrolyzes different substrates are not clear yet. Understanding the catalytic mechanism(s) of h-PON1 is important in developing the enzyme for therapeutic use. Literature suggests that R/Q polymorphism at position 192 in h-PON1 dramatically modulates the substrate specificity of the enzyme. In order to understand the role of the amino acid residue at position 192 of h-PON1 in its various hydrolytic activities, site-specific mutagenesis at position 192 was done in this study. The mutant enzymes were produced using Escherichia coli expression system and their hydrolytic activities were compared against a panel of substrates. Molecular dynamics simulation studies were employed on selected recombinant h-PON1 (rh-PON1) mutants to understand the effect of amino acid substitutions at position 192 on the structural features of the active site of the enzyme. Our results suggest that, depending on the type of substrate, presence of a particular amino acid residue at position 192 differentially alters the micro-environment of the active site of the enzyme resulting in the engagement of different subsets of amino acid residues in the binding and the processing of substrates. The result advances our understanding of the catalytic mechanism of h-PON1. PMID:26829396

  15. Mechanical Consequences of Cell-Wall Turnover in the Elongation of a Gram-Positive Bacterium

    PubMed Central

    Misra, Gaurav; Rojas, Enrique R.; Gopinathan, Ajay; Huang, Kerwyn Casey

    2013-01-01

    A common feature of walled organisms is their exposure to osmotic forces that challenge the mechanical integrity of cells while driving elongation. Most bacteria rely on their cell wall to bear osmotic stress and determine cell shape. Wall thickness can vary greatly among species, with Gram-positive bacteria having a thicker wall than Gram-negative bacteria. How wall dimensions and mechanical properties are regulated and how they affect growth have not yet been elucidated. To investigate the regulation of wall thickness in the rod-shaped Gram-positive bacterium Bacillus subtilis, we analyzed exponentially growing cells in different media. Using transmission electron and epifluorescence microscopy, we found that wall thickness and strain were maintained even between media that yielded a threefold change in growth rate. To probe mechanisms of elongation, we developed a biophysical model of the Gram-positive wall that balances the mechanical effects of synthesis of new material and removal of old material through hydrolysis. Our results suggest that cells can vary their growth rate without changing wall thickness or strain by maintaining a constant ratio of synthesis and hydrolysis rates. Our model also indicates that steady growth requires wall turnover on the same timescale as elongation, which can be driven primarily by hydrolysis rather than insertion. This perspective of turnover-driven elongation provides mechanistic insight into previous experiments involving mutants whose growth rate was accelerated by the addition of lysozyme or autolysin. Our approach provides a general framework for deconstructing shape maintenance in cells with thick walls by integrating wall mechanics with the kinetics and regulation of synthesis and turnover. PMID:23746506

  16. Cloud-radiation interactions - Effects of cirrus optical thickness feedbacks

    NASA Technical Reports Server (NTRS)

    Somerville, Richard C. J.; Iacobellis, Sam

    1987-01-01

    The paper is concerned with a cloud-radiation feedback mechanism which may be an important component of the climate changes expected from increased atmospheric concentrations of carbon dioxide and other trace greenhouse gases. A major result of the study is that cirrus cloud optical thickness feedbacks may indeed tend to increase the surface warming due to trace gas increases. However, the positive feedback from cirrus appears to be generally weaker than the negative effects due to lower clouds. The results just confirm those of earlier research indicating that the net effect of cloud optical thickness feedbacks may be a negative feedback which may substantially (by a factor of about 2) reduce the surface warming due to the doubling of CO2, even in the presence of cirrus clouds.

  17. Keratinocyte-derived IL-24 plays a role in the positive feedback regulation of epidermal inflammation in response to environmental and endogenous toxic stressors

    SciTech Connect

    Jin, Sun Hee; Choi, Dalwoong; Chun, Young-Jin; Noh, Minsoo

    2014-10-15

    Keratinocytes are the major cellular components of human epidermis and play a key role in the modulating cutaneous inflammation and toxic responses. In human chronic skin diseases, the common skin inflammatory phenotypes like skin barrier disruption and epidermal hyperplasia are manifested in epidermal keratinocytes by interactions with T helper (Th) cells. To find a common gene expression signature of human keratinocytes in chronic skin diseases, we performed a whole genome microarray analysis on normal human epidermal keratinocytes (NHKs) treated with IFNγ, IL-4, IL-17A or IL-22, major cytokines from Th1, Th2, Th17 or Th22 cells, respectively. The microarray results showed that the four genes, IL-24, PDZK1IP1, H19 and filaggrin, had common expression profiles in NHKs exposed to Th cell cytokines. In addition, the acute phase pro-inflammatory cytokines, IL-1β, IL-6 and TNFα, also change the gene transcriptional profile of IL-24, PDZK1IP1, H19, and filaggrin in NHKs as those of Th cytokines. Therefore, the signature gene set, consisting of IL-24, PDZK1IP1, H19, and filaggrin, provides essential insights for understanding the process of cutaneous inflammation and toxic responses. We demonstrate that environmental toxic stressors, such as chemical irritants and ultraviolet irradiation stimulate the production of IL-24 in NHKs. IL-24 stimulates the JAK1-STAT3 and MAPK pathways in NHKs, and promotes the secretion of pro-inflammatory mediators IL-8, PGE2, and MMP-1. These results suggest that keratinocyte-derived IL-24 participates in the positive feedback regulation of epidermal inflammation in response to both endogenous and environmental toxic stressors. - Highlights: • Cutaneous inflammatory gene signature consists of PDZK1IP1, IL-24, H19 and filaggrin. • Pro-inflammatory cytokines increase IL-24 production in human keratinocytes. • Environmental toxic stressors increase IL-24 production in human keratinocytes. • IL-24 stimulates human keratinocytes to

  18. [Long-term effects of home mechanical ventilation with positive pressure using a nasal mask].

    PubMed

    Escarrabill, J; Estopà, R; Robert, D; Casolivé, V; Manresa, F

    1991-10-01

    Home mechanical ventilation (HMV) is an efficient alternative in the treatment of patients with chronic respiratory failure secondary to restrictive mechanical disorders (neuromuscular disease, such as Duchenne's disease, thorax deformities due to kyphoscoliosis or tuberculosis sequelae). The case of a patient with severe kyphoscoliosis in the phase of chronic respiratory failure (PaO2 34 mmHg and PaCO2 61 mmHg, breathing ambient air) is presented in which, following the failure of negative pressure mechanical ventilation ("poncho"), positive pressure ventilation was tested with a silicon made-to-measure nasal mask as the access via. Adaptation to HMV was good with the patient using the ventilation nightly. Following 12 months of treatment the patient is able to carry out everyday activities and arterial gasometry breathing ambient air is PaO2 77 mmHg and PaCO2 43 mmHg. PMID:1961049

  19. Global desertification: Drivers and feedbacks

    NASA Astrophysics Data System (ADS)

    D'Odorico, Paolo; Bhattachan, Abinash; Davis, Kyle F.; Ravi, Sujith; Runyan, Christiane W.

    2013-01-01

    Desertification is a change in soil properties, vegetation or climate, which results in a persistent loss of ecosystem services that are fundamental to sustaining life. Desertification affects large dryland areas around the world and is a major cause of stress in human societies. Here we review recent research on the drivers, feedbacks, and impacts of desertification. A multidisciplinary approach to understanding the drivers and feedbacks of global desertification is motivated by our increasing need to improve global food production and to sustainably manage ecosystems in the context of climate change. Classic desertification theories look at this process as a transition between stable states in bistable ecosystem dynamics. Climate change (i.e., aridification) and land use dynamics are the major drivers of an ecosystem shift to a “desertified” (or “degraded”) state. This shift is typically sustained by positive feedbacks, which stabilize the system in the new state. Desertification feedbacks may involve land degradation processes (e.g., nutrient loss or salinization), changes in rainfall regime resulting from land-atmosphere interactions (e.g., precipitation recycling, dust emissions), or changes in plant community composition (e.g., shrub encroachment, decrease in vegetation cover). We analyze each of these feedback mechanisms and discuss their possible enhancement by interactions with socio-economic drivers. Large scale effects of desertification include the emigration of “environmental refugees” displaced from degraded areas, climatic changes, and the alteration of global biogeochemical cycles resulting from the emission and long-range transport of fine mineral dust. Recent research has identified some possible early warning signs of desertification, which can be used as indicators of resilience loss and imminent shift to desert-like conditions. We conclude with a brief discussion on some desertification control strategies implemented in different

  20. Anteroposterior positioning of the tibial component and its effect on the mechanics of patellofemoral contact.

    PubMed

    Didden, K; Luyckx, T; Bellemans, J; Labey, L; Innocenti, B; Vandenneucker, H

    2010-10-01

    The biomechanics of the patellofemoral joint can become disturbed during total knee replacement by alterations induced by the position and shape of the different prosthetic components. The role of the patella and femoral trochlea has been well studied. We have examined the effect of anterior or posterior positioning of the tibial component on the mechanisms of patellofemoral contact in total knee replacement. The hypothesis was that placing the tibial component more posteriorly would reduce patellofemoral contact stress while providing a more efficient lever arm during extension of the knee. We studied five different positions of the tibial component using a six degrees of freedom dynamic knee simulator system based on the Oxford rig, while simulating an active knee squat under physiological loading conditions. The patellofemoral contact force decreased at a mean of 2.2% for every millimetre of posterior translation of the tibial component. Anterior positions of the tibial component were associated with elevation of the patellofemoral joint pressure, which was particularly marked in flexion > 90°. From our results we believe that more posterior positioning of the tibial component in total knee replacement would be beneficial to the patellofemoral joint. PMID:20884990

  1. Positive coping styles and perigenual ACC volume: two related mechanisms for conferring resilience?

    PubMed

    Holz, Nathalie E; Boecker, Regina; Jennen-Steinmetz, Christine; Buchmann, Arlette F; Blomeyer, Dorothea; Baumeister, Sarah; Plichta, Michael M; Esser, Günter; Schmidt, Martin; Meyer-Lindenberg, Andreas; Banaschewski, Tobias; Brandeis, Daniel; Laucht, Manfred

    2016-05-01

    Stress exposure has been linked to increased rates of depression and anxiety in adults, particularly in females, and has been associated with maladaptive changes in the anterior cingulate cortex (ACC), which is an important brain structure involved in internalizing disorders. Coping styles are important mediators of the stress reaction by establishing homeostasis, and may thus confer resilience to stress-related psychopathology. Anatomical scans were acquired in 181 healthy participants at age 25 years. Positive coping styles were determined using a self-report questionnaire (German Stress Coping Questionnaire, SVF78) at age 22 years. Adult anxiety and depression symptoms were assessed at ages 22, 23 and 25 years with the Young Adult Self-Report. Information on previous internalizing diagnoses was obtained by diagnostic interview (2-19 years). Positive coping styles were associated with increased ACC volume. ACC volume and positive coping styles predicted anxiety and depression in a sex-dependent manner with increased positive coping and ACC volume being related to lower levels of psychopathology in females, but not in males. These results remained significant when controlled for previous internalizing diagnoses. These findings indicate that positive coping styles and ACC volume are two linked mechanisms, which may serve as protective factors against internalizing disorders. PMID:26743466

  2. Thermal-chemical-mechanical feedback during fluid-rock interactions: Implications for chemical transport and scales of equilibria in the crust

    SciTech Connect

    Dutrow, Barbara

    2008-08-13

    Our research evaluates the hypothesis that feedback amongst thermal-chemical-mechanical processes operative in fluid-rock systems alters the fluid flow dynamics of the system which, in turn, affects chemical transport and temporal and spatial scales of equilibria, thus impacting the resultant mineral textural development of rocks. Our methods include computational experimentation and detailed analyses of fluid-infiltrated rocks from well-characterized terranes. This work focuses on metamorphic rocks and hydrothermal systems where minerals and their textures are utilized to evaluate pressure (P), temperature (T), and time (t) paths in the evolution of mountain belts and ore deposits, and to interpret tectonic events and the timing of these events. Our work on coupled processes also extends to other areas where subsurface flow and transport in porous media have consequences such as oil and gas movement, geothermal system development, transport of contaminants, nuclear waste disposal, and other systems rich in fluid-rock reactions. Fluid-rock systems are widespread in the geologic record. Correctly deciphering the products resulting from such systems is important to interpreting a number of geologic phenomena. These systems are characterized by complex interactions involving time-dependent, non-linear processes in heterogeneous materials. While many of these interactions have been studied in isolation, they are more appropriately analyzed in the context of a system with feedback. When one process impacts another process, time and space scales as well as the overall outcome of the interaction can be dramatically altered. Our goals to test this hypothesis are: to develop and incorporate algorithms into our 3D heat and mass transport code to allow the effects of feedback to be investigated numerically, to analyze fluid infiltrated rocks from a variety of terranes at differing P-T conditions, to identify subtle features of the infiltration of fluids and/or feedback, and

  3. Mechatronic Scanning System with Integrated Micro Electro Mechanical System Position Sensors

    NASA Astrophysics Data System (ADS)

    Stavrov, Vladimir; Chakarov, Dimitar; Shulev, Assen; Tsveov, Mihail

    2016-06-01

    In this paper, a study of a mechatronic scanning system for application in the microbiology, microelectronics research, chemistry, etc. is presented. Integrated silicon micro electro mechanical system (MEMS) position sensor is used for monitoring the displacement of the scanning system. The utilized silicon MEMS sensors with sidewall embedded piezoresistors possess a number of key advantages such as high sensitivity, low noise and extremely low temperature dependence. Design of 2D scanning system with a travel range of 22 × 22 μm2 has been presented in present work. This system includes a Compliant Transmission Mechanism, (CTM) designed as a complex elastic mechanism, comprising four parallelograms. Computer aided desigh (CAD) model and finite element analysis (FEA) of the Compliant Transmission Mechanism mechanisms have been carried out. A prototype of the scanning system is fabricated, based on CAD model. An experimental set-up of an optical system and a correlation technique for digital image processing have been used for testing the scanning system prototype. Results of the experimental investigations of the prototyped scanning system are also presented.

  4. The slider motion error analysis by positive solution method in parallel mechanism

    NASA Astrophysics Data System (ADS)

    Ma, Xiaoqing; Zhang, Lisong; Zhu, Liang; Yang, Wenguo; Hu, Penghao

    2016-01-01

    Motion error of slider plays key role in 3-PUU parallel coordinates measuring machine (CMM) performance and influence the CMM accuracy, which attracts lots of experts eyes in the world, Generally, the analysis method is based on the view of space 6-DOF. Here, a new analysis method is provided. First, the structure relation of slider and guideway can be abstracted as a 4-bar parallel mechanism. So, the sliders can be considered as moving platform in parallel kinematic mechanism PKM. Its motion error analysis is also transferred to moving platform position analysis in PKM. Then, after establishing the positive and negative solutions, some existed theory and technology for PKM can be applied to analyze slider straightness motion error and angular motion error simultaneously. Thirdly, some experiments by autocollimator are carried out to capture the original error data about guideway its own error, the data can be described as straightness error function by fitting curvilinear equation. Finally, the Straightness error of two guideways are considered as the variation of rod length in parallel mechanism, the slider's straightness error and angular error can be obtained by putting data into the established model. The calculated result is generally consistent with experiment result. The idea will be beneficial on accuracy calibration and error correction of 3-PUU CMM and also provides a new thought to analyze kinematic error of guideway in precision machine tool and precision instrument.

  5. Panel positioning error and support mechanism for a 30-m THz radio telescope

    NASA Astrophysics Data System (ADS)

    Yang, De-Hua; Okoh, Daniel; Zhou, Guo-Hua; Li, Ai-Hua; Li, Guo-Ping; Cheng, Jing-Quan

    2011-06-01

    A 30-m TeraHertz (THz) radio telescope is proposed to operate at 200 μm with an active primary surface. This paper presents sensitivity analysis of active surface panel positioning errors with optical performance in terms of the Strehl ratio. Based on Ruze's surface error theory and using a Monte Carlo simulation, the effects of six rigid panel positioning errors, such as piston, tip, tilt, radial, azimuthal and twist displacements, were directly derived. The optical performance of the telescope was then evaluated using the standard Strehl ratio. We graphically illustrated the various panel error effects by presenting simulations of complete ensembles of full reflector surface errors for the six different rigid panel positioning errors. Study of the panel error sensitivity analysis revealed that the piston error and tilt/tip errors are dominant while the other rigid errors are much less important. Furthermore, as indicated by the results, we conceived of an alternative Master-Slave Concept-based (MSC-based) active surface by implementating a special Series-Parallel Concept-based (SPC-based) hexapod as the active panel support mechanism. A new 30-m active reflector based on the two concepts was demonstrated to achieve correction for all the six rigid panel positioning errors in an economically feasible way.

  6. β-Lactam Resistance Mechanisms: Gram-Positive Bacteria and Mycobacterium tuberculosis.

    PubMed

    Fisher, Jed F; Mobashery, Shahriar

    2016-01-01

    The value of the β-lactam antibiotics for the control of bacterial infection has eroded with time. Three Gram-positive human pathogens that were once routinely susceptible to β-lactam chemotherapy-Streptococcus pneumoniae, Enterococcus faecium, and Staphylococcus aureus-now are not. Although a fourth bacterium, the acid-fast (but not Gram-positive-staining) Mycobacterium tuberculosis, has intrinsic resistance to earlier β-lactams, the emergence of strains of this bacterium resistant to virtually all other antibiotics has compelled the evaluation of newer β-lactam combinations as possible contributors to the multidrug chemotherapy required to control tubercular infection. The emerging molecular-level understanding of these resistance mechanisms used by these four bacteria provides the conceptual framework for bringing forward new β-lactams, and new β-lactam strategies, for the future control of their infections. PMID:27091943

  7. Failure of prolactin short loop feedback mechanism to operate in old as compared to young female rats.

    PubMed

    Sarkar, D K; Miki, N; Meites, J

    1983-10-01

    The short loop feedback effect of PRL was studied in young (4-5 months of age) and old (24-26 months of age) ovariectomized rats after a single iv injection of bovine PRL (bPRL, 500 micrograms/100 g BW) or BSA (500 micrograms/100 g BW). Blood samples were collected via intraatrial cannula every 20 min for assay of PRL. Plasma PRL levels in both young and old ovariectomized rats were pulsatile in nature, and showed approximately one PRL pulse per hour. The magnitude of the PRL peaks and concentrations of plasma PRL, but not the number of PRL peaks, were significantly greater in the old than in the young rats. The effect of bPRL on in situ PRL release was studied after verifying that bPRL does not cross-react with rat PRL RIA, but does significantly increase the release of [3H] dopamine from the median eminence in vitro. This latter effect was dose dependent. In young rats, a single injection of bPRL minimally reduced the concentration of plasma PRL between 100 min and 5 h, but by 22-25 h it decreased plasma PRL to approximately one third of preinjection levels. The magnitude of the PRL pulses, but not the pulse frequency was significantly reduced after administration of bPRL treatment to young rats. Treatment with BSA did not alter the concentration of plasma PRL or the magnitude and frequency of the PRL pulses in young rats. In old rats, plasma PRL concentrations and the frequency and magnitude of the PRL pulses were not significantly decreased after injection of either bPRL or BSA. Thus, the feedback inhibition of PRL on PRL release may not be operative in old rats. The loss of the short loop feedback inhibition of PRL is believed to be due to the reduction in hypothalamic dopaminergic activity previously reported by our and other laboratories in old rats. PMID:6617580

  8. Reward feedback accelerates motor learning.

    PubMed

    Nikooyan, Ali A; Ahmed, Alaa A

    2015-01-15

    Recent findings have demonstrated that reward feedback alone can drive motor learning. However, it is not yet clear whether reward feedback alone can lead to learning when a perturbation is introduced abruptly, or how a reward gradient can modulate learning. In this study, we provide reward feedback that decays continuously with increasing error. We asked whether it is possible to learn an abrupt visuomotor rotation by reward alone, and if the learning process could be modulated by combining reward and sensory feedback and/or by using different reward landscapes. We designed a novel visuomotor learning protocol during which subjects experienced an abruptly introduced rotational perturbation. Subjects received either visual feedback or reward feedback, or a combination of the two. Two different reward landscapes, where the reward decayed either linearly or cubically with distance from the target, were tested. Results demonstrate that it is possible to learn from reward feedback alone and that the combination of reward and sensory feedback accelerates learning. An analysis of the underlying mechanisms reveals that although reward feedback alone does not allow for sensorimotor remapping, it can nonetheless lead to broad generalization, highlighting a dissociation between remapping and generalization. Also, the combination of reward and sensory feedback accelerates learning without compromising sensorimotor remapping. These findings suggest that the use of reward feedback is a promising approach to either supplement or substitute sensory feedback in the development of improved neurorehabilitation techniques. More generally, they point to an important role played by reward in the motor learning process. PMID:25355957

  9. Cryogenic Optical Position Encoders for Mechanisms in the JWST Optical Telescope Element Simulator (OSIM)

    NASA Technical Reports Server (NTRS)

    Leviton, Douglas B.; Anderjaska, Thomas; Badger, James (Inventor); Capon, Tom; Davis, CLinton; Dicks, Brent (Inventor); Eichhorn, William; Garza, Mario; Guishard, Corina; Haghani, Shadan; Hakun, Claef; Haney, Paul; Happs, David (Inventor); Hovmand, Lars; Kadari, Madhu; Kirk, Jeffrey; Nyquist, Richard (Inventor); Robinson, F. David; Sullivan, Joseph (Inventor); Wilson, Erin

    2013-01-01

    The JWST Optical Telescope Element Simulator (OSIM) is a configurable, cryogenic, optical stimulus for high fidelity ground characterization and calibration of JWST's flight instruments. OSIM and its associated Beam Image Analyzer (BIA) contain several ultra-precise, cryogenic mechanisms that enable OSIM to project point sources into the instruments according to the same optical prescription as the flight telescope images stars - correct in focal surface position and chief ray angle. OSIM's and BIA's fifteen axes of mechanisms navigate according to redundant, cryogenic, absolute, optical encoders - 32 in all operating at or below 100 K. OSIM's encoder subsystem, the engineering challenges met in its development, and the encoders' sub-micron and sub-arcsecond performance are discussed.

  10. A sharp-switching device with free surface and buried gates based on band modulation and feedback mechanisms

    NASA Astrophysics Data System (ADS)

    Solaro, Y.; Fonteneau, P.; Legrand, C. A.; Fenouillet-Beranger, C.; Ferrari, P.; Cristoloveanu, S.

    2016-02-01

    We propose and demonstrate experimentally a band-modulation device with extremely sharp switching capability. The Z3-FET (Zero gate, Zero swing and Zero impact ionization) has no top gate, is processed with FDSOI CMOS technology, and makes use of two adjacent buried ground planes acting as back gates. The buried gates emulate respectively N+ and P+ regions in the undoped body, forming a virtual thyristor-like NPNP structure with feedback operation. Vertical output IA-VA and transfer IA-VG characteristics over more than 8 decades of current are measured with relatively low gate and drain bias (<3 V).

  11. Feedback Sandwiches Affect Perceptions but Not Performance

    ERIC Educational Resources Information Center

    Parkes, Jay; Abercrombie, Sara; McCarty, Teresita

    2013-01-01

    The feedback sandwich technique-make positive comments; provide critique; end with positive comments-is commonly recommended to feedback givers despite scant evidence of its efficacy. These two studies (N = 20; N = 350) of written peer feedback with third-year medical students on clinical patient note-writing assignments indicate that students…

  12. Modelling ecogeomorphological feedback mechanisms for the analysis of land degradation patterns of a semi-arid shrubland-grassland transition zone

    NASA Astrophysics Data System (ADS)

    Mueller, Eva Nora; Tietjen, Britta; Turnbull, Laura

    2013-04-01

    Land degradation through water erosion is driven by ecogeomorphological processes which may alter transfer paths at the hillslope, the soil-hydraulic conditions of the upper soil layers and the vegetation structure of the hillslope. These processes are interlinked with each other through augmenting feedback mechanisms in such a way that a small change in land use (e.g. temporary overgrazing, cattle trails) may result in a re-organisation of the affected landscape. A grassland-shrubland transition zone in the south-western United States is being investigated here for soil-vegetation-transfer feedback mechanisms. For this purpose, an ecogeomorphological, process-based model has been developed which simulates the redistribution of sediments and nutrients during high-intensity rainstorms in 1-sec time steps, the soil moisture and transpiration dynamics in daily time steps, and the vegetation dynamics (establishment, growth, mortality) in 14-day time steps for a high-resolution grid of 1x1 m2. Through long-term modelling and the modelling of extremes (prolonged droughts or overgrazing), the numerical approach is employed to analyse which types of feedbacks may occur and may trigger persistent vegetation change and land degradation of the hillslope. Using this model it is for the first time possible to couple the occurrence of self-organisational patterns of moisture and soil resource availability of a hillslope with redistribution processes that occur during high-intensity storms. The model thus closes the gap of current modelling approaches that either investigate only individual extreme events or models the long-term dynamics of a landscape without including the detailed erosion processes.

  13. The Mechanisms of Virulence Regulation by Small Noncoding RNAs in Low GC Gram-Positive Pathogens

    PubMed Central

    Pitman, Stephanie; Cho, Kyu Hong

    2015-01-01

    The discovery of small noncoding regulatory RNAs (sRNAs) in bacteria has grown tremendously recently, giving new insights into gene regulation. The implementation of computational analysis and RNA sequencing has provided new tools to discover and analyze potential sRNAs. Small regulatory RNAs that act by base-pairing to target mRNAs have been found to be ubiquitous and are the most abundant class of post-transcriptional regulators in bacteria. The majority of sRNA studies has been limited to E. coli and other gram-negative bacteria. However, examples of sRNAs in gram-positive bacteria are still plentiful although the detailed gene regulation mechanisms behind them are not as well understood. Strict virulence control is critical for a pathogen’s survival and many sRNAs have been found to be involved in that process. This review outlines the targets and currently known mechanisms of trans-acting sRNAs involved in virulence regulation in various gram-positive pathogens. In addition, their shared characteristics such as CU interaction motifs, the role of Hfq, and involvement in two-component regulators, riboswitches, quorum sensing, or toxin/antitoxin systems are described. PMID:26694351

  14. Positive extreme responding after cognitive therapy for depression: Correlates and potential mechanisms.

    PubMed

    Forand, Nicholas R; Strunk, Daniel R; DeRubeis, Robert J

    2016-08-01

    "Extreme responding" is the tendency to endorse extreme responses on self-report measures (e.g., 1s and 7s on a 7-point scale). It has been linked to depressive relapse after cognitive therapy (CT), but the mechanisms are unknown. Moreover, findings of positive extreme responding (PER) predicting depressive relapse do not support the original hypothesis of "extreme" negative thinking leading to extreme negative emotional reactions. We assessed the relationships between post-treatment PER on the Dysfunctional Attitudes Scale (DAS) and Attributional Style Questionnaire (ASQ) and these constructs: coping skills, in-session performance of cognitive therapy skills, age, and estimated IQ. Significant correlates were entered into a model predicting rate of relapse to determine whether these constructs explained the relationship between PER and relapse. The sample consisted of 60 individuals who participated in CT for moderate to severe depression. Results indicated the following relationships: a negative correlation between ASQ PER and IQ, negative correlations between DAS PER and performance of CT skills and planning coping, and a positive correlation between DAS PER and behavioral disengagement coping. IQ scores fully accounted for the relationship between ASQ PER and relapse. These results suggest two potential mechanisms linking PER to relapse: cognitive limitations and coping deficits/cognitive avoidance. PMID:27236074

  15. Using DNA mechanics to predict intrinsic and extrinsic nucleosome positioning signals

    NASA Astrophysics Data System (ADS)

    Morozov, Alexandre

    2008-03-01

    In eukaryotic genomes, nucleosomes function to compact DNA and to regulate access to it both by simple physical occlusion and by providing the substrate for numerous covalent epigenetic tags. While nucleosome positions in vitro are determined by sequence alone, in vivo competition with other DNA-binding factors and action of chromatin remodeling enzymes play a role that needs to be quantified. We developed a biophysical, DNA mechanics-based model for the sequence dependence of DNA bending energies, and validated it against a collection of in vitro free energies of nucleosome formation and a nucleosome crystal structure; we also successfully designed both strong and poor histone binding sequences ab initio. For in vivo data from S.cerevisiae, the strongest positioning signal came from the competition with other factors rather than intrinsic nucleosome sequence preferences. Based on sequence alone, our model predicts that functional transcription factor binding sites tend to be covered by nucleosomes, yet are uncovered in vivo because functional sites cluster within a single nucleosome footprint and thus make transcription factors bind cooperatively. Similarly a weak enhancement of nucleosome binding in the TATA region becomes a strong depletion when the TATA-binding protein is included, in quantitative agreement with experiment. Our model distinguishes multiple ways in which genomic sequence influences nucleosome positions, and thus provides alternative explanations for several genome-wide experimental findings. In the future our approach will be used to rationally alter gene expression levels in model systems through redesign of nucleosome occupancy profiles.

  16. Examination of the mechanism of sucrose synthetase by positional isotope exchange

    SciTech Connect

    Singh, A.N.; Hester, L.S.; Raushel, F.M.

    1987-02-25

    The mechanism of the sucrose synthetase reaction has been probed by the technique of positional isotope exchange. (beta-/sup 18/O/sub 2/, alpha beta-/sup 18/O)UDP-Glc has been synthesized starting from oxygen-18-labeled phosphate and the combined activities of carbamate kinase, hexokinase, phosphoglucomutase, and uridine diphosphoglucose pyrophosphorylase. The oxygen-18 at the alpha beta-bridge position of the labeled UDP-Glc has been shown to cause a 0.014 ppm upfield chemical shift in the 31P NMR spectrum of both the alpha- and beta-phosphorus atoms in UDP-Glc relative to the unlabeled compound. The chemical shift induced by each of the beta-nonbridge oxygen-18 atoms was 0.030 ppm. Incubation of (beta-/sup 18/O/sub 2/, alpha beta-/sup 18/O)UDP-Glc with sucrose synthetase in the presence and absence of 2,5-anhydromannitol did not result in any significant exchange of an oxygen-18 from the beta-nonbridge position to the anomeric oxygen of the glucose moiety. It can thus be concluded that either sucrose synthetase does not catalyze the cleavage of the scissile carbon-oxygen bond of UDP-Glc in the absence of fructose or, alternatively, the beta-phosphoryl group of the newly formed UDP is rotationally immobilized.

  17. Dynamic Ruptures on a Frictional Interface with Off-Fault Brittle Damage: Feedback Mechanisms and Effects on Slip and Near-Fault Motion

    NASA Astrophysics Data System (ADS)

    Xu, Shiqing; Ben-Zion, Yehuda; Ampuero, Jean-Paul; Lyakhovsky, Vladimir

    2015-05-01

    The spontaneous generation of brittle rock damage near and behind the tip of a propagating rupture can produce dynamic feedback mechanisms that modify significantly the rupture properties, seismic radiation, and generated fault zone structure. In this work, we study such feedback mechanisms for single rupture events and their consequences for earthquake physics and various possible observations. This is done through numerical simulations of in-plane dynamic ruptures on a frictional fault with bulk behavior governed by a brittle damage rheology that incorporates reduction of elastic moduli in off-fault yielding regions. The model simulations produce several features that modify key properties of the ruptures, local wave propagation, and fault zone damage. These include (1) dynamic generation of near-fault regions with lower elastic properties, (2) dynamic changes of normal stress on the fault, (3) rupture transition from crack-like to a detached pulse, (4) emergence of a rupture mode consisting of a train of pulses, (5) quasi-periodic modulation of slip rate on the fault, and (6) asymmetric near-fault ground motion with higher amplitude and longer duration on the side with reduced elastic moduli. The results can have significant implications to multiple topics ranging from rupture directivity and local amplification of seismic motion to near-fault tremor-like signals.

  18. Dynamic Ruptures on a Frictional Interface with Off-Fault Brittle Damage: Feedback Mechanisms and Effects on Slip and Near-Fault Motion

    NASA Astrophysics Data System (ADS)

    Xu, Shiqing; Ben-Zion, Yehuda; Ampuero, Jean-Paul; Lyakhovsky, Vladimir

    2014-09-01

    The spontaneous generation of brittle rock damage near and behind the tip of a propagating rupture can produce dynamic feedback mechanisms that modify significantly the rupture properties, seismic radiation, and generated fault zone structure. In this work, we study such feedback mechanisms for single rupture events and their consequences for earthquake physics and various possible observations. This is done through numerical simulations of in-plane dynamic ruptures on a frictional fault with bulk behavior governed by a brittle damage rheology that incorporates reduction of elastic moduli in off-fault yielding regions. The model simulations produce several features that modify key properties of the ruptures, local wave propagation, and fault zone damage. These include (1) dynamic generation of near-fault regions with lower elastic properties, (2) dynamic changes of normal stress on the fault, (3) rupture transition from crack-like to a detached pulse, (4) emergence of a rupture mode consisting of a train of pulses, (5) quasi-periodic modulation of slip rate on the fault, and (6) asymmetric near-fault ground motion with higher amplitude and longer duration on the side with reduced elastic moduli. The results can have significant implications to multiple topics ranging from rupture directivity and local amplification of seismic motion to near-fault tremor-like signals.

  19. Mechanical strain can switch the sign of quantum capacitance from positive to negative.

    PubMed

    Hanlumyuang, Yuranan; Li, Xiaobao; Sharma, Pradeep

    2014-11-14

    Quantum capacitance is a fundamental quantity that can directly reveal many-body interactions among electrons and is expected to play a critical role in nanoelectronics. One of the many tantalizing recent physical revelations about quantum capacitance is that it can possess a negative value, hence allowing for the possibility of enhancing the overall capacitance in some particular material systems beyond the scaling predicted by classical electrostatics. Using detailed quantum mechanical simulations, we found an intriguing result that mechanical strains can tune both signs and values of quantum capacitance. We used a small coaxially gated carbon nanotube as a paradigmatical capacitor system and showed that, for the range of mechanical strain considered, quantum capacitance can be adjusted from very large positive to very large negative values (in the order of plus/minus hundreds of attofarads), compared to the corresponding classical geometric value (0.31035 aF). This finding opens novel avenues in designing quantum capacitance for applications in nanosensors, energy storage, and nanoelectronics. PMID:25259466

  20. Control your anger! The neural basis of aggression regulation in response to negative social feedback.

    PubMed

    Achterberg, Michelle; van Duijvenvoorde, Anna C K; Bakermans-Kranenburg, Marian J; Crone, Eveline A

    2016-05-01

    Negative social feedback often generates aggressive feelings and behavior. Prior studies have investigated the neural basis of negative social feedback, but the underlying neural mechanisms of aggression regulation following negative social feedback remain largely undiscovered. In the current study, participants viewed pictures of peers with feedback (positive, neutral or negative) to the participant's personal profile. Next, participants responded to the peer feedback by pressing a button, thereby producing a loud noise toward the peer, as an index of aggression. Behavioral analyses showed that negative feedback led to more aggression (longer noise blasts). Conjunction neuroimaging analyses revealed that both positive and negative feedback were associated with increased activity in the medial prefrontal cortex (PFC) and bilateral insula. In addition, more activation in the right dorsal lateral PFC (dlPFC) during negative feedback vs neutral feedback was associated with shorter noise blasts in response to negative social feedback, suggesting a potential role of dlPFC in aggression regulation, or top-down control over affective impulsive actions. This study demonstrates a role of the dlPFC in the regulation of aggressive social behavior. PMID:26755768

  1. A cfr-positive clinical staphylococcal isolate from India with multiple mechanisms of linezolid-resistance

    PubMed Central

    Rajan, Vineeth; Kumar, Vijay Gowdara Shankarappa; Gopal, Shubha

    2014-01-01

    Background & objectives: Linezolid, a member of the oxazolidinone class of antibiotics, has been an effective therapeutic option to treat severe infections caused by multidrug resistant Gram positive bacteria. Emergence of linezolid resistant clinical strains is a serious issue in the healthcare settings worldwide. We report here the molecular characterization of a linezolid resistant clinical isolate of Staphylococcus haemolyticus from India. Methods: The species of the clinical isolate was identified by 16S rRNA gene sequencing. The minimum inhibitory concentrations (MICs) of linezolid, clindamycin, chloramphenicol and oxacillin were determined by E-test method. To elucidate the mechanism of linezolid-resistance, presence of cfr gene (chloramphenicol florfenicol resistance) and mutations in 23S rRNA and ribosomal proteins (L3, L4 and L22) were investigated. Staphylococcal Cassette Chromosome mec (SCCmec) typing was performed by multiplex PCR. Results: The study documented a rare clinical S. haemolyticus strain with three independent mechanisms of linezolid-resistance. The strain carried cfr gene, the only known transmissible mechanism of linezolid-resistance. The strain also possessed resistance-conferring mutations such as G2576T in domain V of 23S rRNA gene and Met156Thr in L3 ribosomal protein. The other ribosomal proteins (L4 and L22) did not exhibit mutations accountable for linezolid-resistance. Restriction digestion by NheI revealed that all the alleles of 23S rRNA gene were mutated. The isolate showed elevated MIC values (>256 μg ml-1 of linezolid, clindamycin, chloramphenicol and oxacillin. Methicillin resistance was conferred by type I SCCmec element. The strain also harboured lsa(B) gene which encodes an ABC transporter that can efflux clindamycin. Interpretation & conclusions: The present study reports the first clinical strain from India with transmissible and multiple mechanisms of linezolid-resistance. Judicious use of linezolid in clinical

  2. Autocycling and increase in intrinsic positive end-expiratory pressure during mechanical ventilation.

    PubMed

    Harboe, S; Hjalmarsson, S; Søreide, E

    2001-11-01

    Modern ventilators are complicated electronic instruments with microprocessors and software, with the possibility of technical errors and problems such as autocycling. Despite autocycling being recognized as a problem in textbooks and reviews, there are few reports about autocycling in the literature. We report a case where a sudden increase in respiratory frequency due to autocycling resulted in a dangerous increase in intrinsic positive end-expiratory pressure (intrinsic PEEP, PEEPi). We think our case illustrates that autocycling does occur, but that the exact underlying mechanism may be hard to document and understand for clinicians. To remedy this situation, we suggest that manufacture-independent technical expertise should be established to evaluate incidents and suggest improvements. PMID:11736686

  3. An epidermis-driven mechanism positions and scales stem cell niches in plants

    PubMed Central

    Gruel, Jérémy; Landrein, Benoit; Tarr, Paul; Schuster, Christoph; Refahi, Yassin; Sampathkumar, Arun; Hamant, Olivier; Meyerowitz, Elliot M.; Jönsson, Henrik

    2016-01-01

    How molecular patterning scales to organ size is highly debated in developmental biology. We explore this question for the characteristic gene expression domains of the plant stem cell niche residing in the shoot apical meristem. We show that a combination of signals originating from the epidermal cell layer can correctly pattern the key gene expression domains and notably leads to adaptive scaling of these domains to the size of the tissue. Using live imaging, we experimentally confirm this prediction. The identified mechanism is also sufficient to explain de novo stem cell niches in emerging flowers. Our findings suggest that the deformation of the tissue transposes meristem geometry into an instructive scaling and positional input for the apical plant stem cell niche. PMID:27152324

  4. Solutions to position-dependent mass quantum mechanics for a new class of hyperbolic potentials

    SciTech Connect

    Christiansen, H. R.; Grupo de Física Teórica, State University of Ceara , Av. Paranjana 1700, 60740-903 Fortaleza-CE ; Cunha, M. S.

    2013-12-15

    We analytically solve the position-dependent mass (PDM) 1D Schrödinger equation for a new class of hyperbolic potentials V{sub q}{sup p}(x)=−V{sub 0}(sinh{sup p}x/cosh{sup q}x), p=−2,0,⋯q [see C. A. Downing, J. Math. Phys. 54, 072101 (2013)] among several hyperbolic single- and double-wells. For a solitonic mass distribution, m(x)=m{sub 0} sech{sup 2}(x), we obtain exact analytic solutions to the resulting differential equations. For several members of the class, the quantum mechanical problems map into confluent Heun differential equations. The PDM Poschl-Teller potential is considered and exactly solved as a particular case.

  5. Right heart catheterisation may be cautiously performed through a mechanical valve prosthesis in the tricuspid position.

    PubMed

    Pettit, Stephen; Tsui, Steven; Parameshwar, Jayan

    2016-01-01

    Right heart catheterisation (RHC) may be performed through a mechanical valve prosthesis in the tricuspid position using a partially inflated pulmonary artery flotation catheter. Preprocedural preparation should include an ex vivo trial with an identical valve prosthesis and the type of catheter to be used for the procedure. The operator should expect immediate unloading of the right ventricle due to catheter-associated tricuspid regurgitation, but it is possible to estimate pulmonary vascular resistance using the Fick principle. The risk of catheter entrapment or damage to the prosthetic leaflets during the procedure is likely to be low. This risk may be acceptable to the clinician and the patient if pulmonary vascular resistance must be measured in order to determine eligibility for heart transplantation. PMID:27074812

  6. An epidermis-driven mechanism positions and scales stem cell niches in plants.

    PubMed

    Gruel, Jérémy; Landrein, Benoit; Tarr, Paul; Schuster, Christoph; Refahi, Yassin; Sampathkumar, Arun; Hamant, Olivier; Meyerowitz, Elliot M; Jönsson, Henrik

    2016-01-01

    How molecular patterning scales to organ size is highly debated in developmental biology. We explore this question for the characteristic gene expression domains of the plant stem cell niche residing in the shoot apical meristem. We show that a combination of signals originating from the epidermal cell layer can correctly pattern the key gene expression domains and notably leads to adaptive scaling of these domains to the size of the tissue. Using live imaging, we experimentally confirm this prediction. The identified mechanism is also sufficient to explain de novo stem cell niches in emerging flowers. Our findings suggest that the deformation of the tissue transposes meristem geometry into an instructive scaling and positional input for the apical plant stem cell niche. PMID:27152324

  7. Fast feedback for linear colliders

    SciTech Connect

    Hendrickson, L.; Adolphsen, C.; Allison, S.; Gromme, T.; Grossberg, P.; Himel, T.; Krauter, K.; MacKenzie, R.; Minty, M.; Sass, R.

    1995-05-01

    A fast feedback system provides beam stabilization for the SLC. As the SLC is in some sense a prototype for future linear colliders, this system may be a prototype for future feedbacks. The SLC provides a good base of experience for feedback requirements and capabilities as well as a testing ground for performance characteristics. The feedback system controls a wide variety of machine parameters throughout the SLC and associated experiments, including regulation of beam position, angle, energy, intensity and timing parameters. The design and applications of the system are described, in addition to results of recent performance studies.

  8. A one-dimensional statistical mechanics model for nucleosome positioning on genomic DNA.

    PubMed

    Tesoro, S; Ali, I; Morozov, A N; Sulaiman, N; Marenduzzo, D

    2016-02-01

    The first level of folding of DNA in eukaryotes is provided by the so-called '10 nm chromatin fibre', where DNA wraps around histone proteins (∼10 nm in size) to form nucleosomes, which go on to create a zig-zagging bead-on-a-string structure. In this work we present a one-dimensional statistical mechanics model to study nucleosome positioning within one such 10 nm fibre. We focus on the case of genomic sheep DNA, and we start from effective potentials valid at infinite dilution and determined from high-resolution in vitro salt dialysis experiments. We study positioning within a polynucleosome chain, and compare the results for genomic DNA to that obtained in the simplest case of homogeneous DNA, where the problem can be mapped to a Tonks gas. First, we consider the simple, analytically solvable, case where nucleosomes are assumed to be point-like. Then, we perform numerical simulations to gauge the effect of their finite size on the nucleosomal distribution probabilities. Finally we compare nucleosome distributions and simulated nuclease digestion patterns for the two cases (homogeneous and sheep DNA), thereby providing testable predictions of the effect of sequence on experimentally observable quantities in experiments on polynucleosome chromatin fibres reconstituted in vitro. PMID:26871546

  9. Using RFID Positioning Technology to Construct an Automatic Rehabilitation Scheduling Mechanism.

    PubMed

    Wang, Ching-Sheng; Hung, Lun-Ping; Yen, Neil Y

    2016-01-01

    Accurately and efficiently identifying the location of patients during the course of rehabilitation is an important issue. Wireless transmission technology can reach this goal. Tracking technologies such as RFID (Radio frequency identification) can support process improvement and improve efficiencies of rehabilitation. There are few published models or methods to solve the problem of positioning and apply this technology in the rehabilitation center. We propose a mechanism to enhance the accuracy of positioning technology and provide information about turns and obstacles on the path; and user-centered services based on location-aware to enhanced quality care in rehabilitation environment. This paper outlines the requirements and the role of RFID in assisting rehabilitation environment. A prototype RFID hospital support tool is established. It is designed to provide assistance for monitoring rehabilitation patients. It can simultaneously calculate the rehabilitant's location and the duration of treatment, and automatically record the rehabilitation course of the rehabilitant, so as to improve the management efficiency of the rehabilitation program. PMID:26573641

  10. A one-dimensional statistical mechanics model for nucleosome positioning on genomic DNA

    NASA Astrophysics Data System (ADS)

    Tesoro, S.; Ali, I.; Morozov, A. N.; Sulaiman, N.; Marenduzzo, D.

    2016-02-01

    The first level of folding of DNA in eukaryotes is provided by the so-called ‘10 nm chromatin fibre’, where DNA wraps around histone proteins (∼10 nm in size) to form nucleosomes, which go on to create a zig-zagging bead-on-a-string structure. In this work we present a one-dimensional statistical mechanics model to study nucleosome positioning within one such 10 nm fibre. We focus on the case of genomic sheep DNA, and we start from effective potentials valid at infinite dilution and determined from high-resolution in vitro salt dialysis experiments. We study positioning within a polynucleosome chain, and compare the results for genomic DNA to that obtained in the simplest case of homogeneous DNA, where the problem can be mapped to a Tonks gas [1]. First, we consider the simple, analytically solvable, case where nucleosomes are assumed to be point-like. Then, we perform numerical simulations to gauge the effect of their finite size on the nucleosomal distribution probabilities. Finally we compare nucleosome distributions and simulated nuclease digestion patterns for the two cases (homogeneous and sheep DNA), thereby providing testable predictions of the effect of sequence on experimentally observable quantities in experiments on polynucleosome chromatin fibres reconstituted in vitro.

  11. Iodothyronine deiodinase gene analysis of the Pacific oyster Crassostrea gigas reveals possible conservation of thyroid hormone feedback regulation mechanism in mollusks

    NASA Astrophysics Data System (ADS)

    Huang, Wen; Xu, Fei; Qu, Tao; Li, Li; Que, Huayong; Zhang, Guofan

    2015-07-01

    Iodothyronine deiodinase catalyzes the initiation and termination of thyroid hormones (THs) effects, and plays a central role in the regulation of thyroid hormone level in vertebrates. In non-chordate invertebrates, only one deiodinase has been identified in the scallop Chlamys farreri. Here, two deiodinases were cloned in the Pacific oyster Crassostrea gigas ( CgDx and CgDy). The characteristic in-frame TGA codons and selenocysteine insertion sequence elements in the oyster deiodinase cDNAs supported the activity of them. Furthermore, seven orthologs of deiodinases were found by a tblastn search in the mollusk Lottia gigantea and the annelid Capitella teleta. A phylogenetic analysis revealed that the deiodinase gene originated from an common ancestor and a clade-specific gene duplication occurred independently during the differentiation of the mollusk, annelid, and vertebrate lineages. The distinct spatiotemporal expression patterns implied functional divergence of the two deiodinases. The expression of CgDx and CgDy was influenced by L-thyroxine T4, and putative thyroid hormone responsive elements were found in their promoters, which suggested that the oyster deiodinases were feedback regulated by TH. Epinephrine stimulated the expression level of CgDx and CgDy, suggesting an interaction effect between different hormones. This study provides the first evidence for the existence of a conserved TH feedback regulation mechanism in mollusks, providing insights into TH evolution.

  12. The mechanism of potent GTP cyclohydrolase I inhibition by 2,4-diamino-6-hydroxypyrimidine: requirement of the GTP cyclohydrolase I feedback regulatory protein.

    PubMed

    Kolinsky, Monica A; Gross, Steven S

    2004-09-24

    Inhibition of GTP cyclohydrolase I (GTPCH) has been used as a selective tool to assess the role of de novo synthesis of (6R)-5,6,7,8-tetrahydro-L-biopterin (BH4) in a biological system. Toward this end, 2,4-diamino-6-hydroxypyrimidine (DAHP) has been used as the prototypical GTPCH inhibitor. Using a novel real-time kinetic microplate assay for GTPCH activity and purified prokaryote-expressed recombinant proteins, we show that potent inhibition by DAHP is not the result of a direct interaction with GTPCH. Rather, inhibition by DAHP in phosphate buffer occurs via an indirect mechanism that requires the presence of GTPCH feedback regulatory protein (GFRP). Notably, GFRP was previously discovered as the essential factor that reconstitutes inhibition of pure recombinant GTPCH by the pathway end product BH4. Thus, DAHP inhibits GTPCH by engaging the endogenous feedback inhibitory system. We further demonstrate that L-Phe fully reverses the inhibition of GTPCH by DAHP/GFRP, which is also a feature in common with inhibition by BH4/GFRP. These findings suggest that DAHP is not an indiscriminate inhibitor of GTPCH in biological systems; instead, it is predicted to preferentially attenuate GTPCH activity in cells that most abundantly express GFRP and/or contain the lowest levels of L-Phe. PMID:15292175

  13. Prediction of clathrate structure type and guest position by molecular mechanics.

    PubMed

    Fleischer, Everly B; Janda, Kenneth C

    2013-05-16

    The clathrate hydrates occur in various types in which the number, size, and shape of the various cages differ. Usually the clathrate type of a specific guest is predicted by the size and shape of the molecular guest. We have developed a methodology to determine the clathrate type employing molecular mechanics with the MMFF force field employing a strategy to calculate the energy of formation of the clathrate from the sum of the guest/cage energies. The clathrate type with the most negative (most stable) energy of formation would be the type predicted (we mainly focused on type I, type II, or bromine type). This strategy allows for a calculation to predict the clathrate type for any cage guest in a few minutes on a laptop computer. It proved successful in predicting the clathrate structure for 46 out of 47 guest molecules. The molecular mechanics calculations also provide a prediction of the guest position within the cage and clathrate structure. These predictions are generally consistent with the X-ray and neutron diffraction studies. By supplementing the diffraction study with molecular mechanics, we gain a more detailed insight regarding the details of the structure. We have also compared MM calculations to studies of the multiple occupancy of the cages. Finally, we present a density functional calculation that demonstrates that the inside of the clathrates cages have a relatively uniform and low electrostatic potential in comparison with the outside oxygen and hydrogen atoms. This implies that van der Waals forces will usually be dominant in the guest-cage interactions. PMID:23600658

  14. Coress feedback

    PubMed Central

    2012-01-01

    This issue of CORESS feedback highlights yet again the importance of checking medications before administration and of adequate handover. Documentation of important medical data including drug allergies, as failed to happen in the case described below, is vital. We are grateful to the clinicians who have provided the material for these reports. The online reporting form is on our website (www.coress.org.uk), which also includes all previous feedback reports. Published contributions will be acknowledged by a ‘Certificate of Contribution’, which may be included in the contributor’s record of continuing professional development.

  15. Fast Feedback in Classroom Practice

    ERIC Educational Resources Information Center

    Emmett, Katrina; Klaassen, Kees; Eijkelhof, Harrie

    2009-01-01

    In this article we describe one application of the fast feedback method (see Berg 2003 "Aust. Sci. Teach. J." 28-34) in secondary mechanics education. Two teachers tried out a particular sequence twice, in consecutive years, once with and once without the use of fast feedback. We found the method to be successful, and the data that we obtained…

  16. Managing uncertainty in soil carbon feedbacks to climate change

    NASA Astrophysics Data System (ADS)

    Bradford, Mark A.; Wieder, William R.; Bonan, Gordon B.; Fierer, Noah; Raymond, Peter A.; Crowther, Thomas W.

    2016-08-01

    Planetary warming may be exacerbated if it accelerates loss of soil carbon to the atmosphere. This carbon-cycle-climate feedback is included in climate projections. Yet, despite ancillary data supporting a positive feedback, there is limited evidence for soil carbon loss under warming. The low confidence engendered in feedback projections is reduced further by the common representation in models of an outdated knowledge of soil carbon turnover. 'Model-knowledge integration' -- representing in models an advanced understanding of soil carbon stabilization -- is the first step to build confidence. This will inform experiments that further increase confidence by resolving competing mechanisms that most influence projected soil-carbon stocks. Improving feedback projections is an imperative for establishing greenhouse gas emission targets that limit climate change.

  17. Mechanistic, Mathematical Model to Predict the Dynamics of Tissue Genesis in Bone Defects via Mechanical Feedback and Mediation of Biochemical Factors

    PubMed Central

    Moore, Shannon R.; Saidel, Gerald M.; Knothe, Ulf; Knothe Tate, Melissa L.

    2014-01-01

    The link between mechanics and biology in the generation and the adaptation of bone has been well studied in context of skeletal development and fracture healing. Yet, the prediction of tissue genesis within - and the spatiotemporal healing of - postnatal defects, necessitates a quantitative evaluation of mechano-biological interactions using experimental and clinical parameters. To address this current gap in knowledge, this study aims to develop a mechanistic mathematical model of tissue genesis using bone morphogenetic protein (BMP) to represent of a class of factors that may coordinate bone healing. Specifically, we developed a mechanistic, mathematical model to predict the dynamics of tissue genesis by periosteal progenitor cells within a long bone defect surrounded by periosteum and stabilized via an intramedullary nail. The emergent material properties and mechanical environment associated with nascent tissue genesis influence the strain stimulus sensed by progenitor cells within the periosteum. Using a mechanical finite element model, periosteal surface strains are predicted as a function of emergent, nascent tissue properties. Strains are then input to a mechanistic mathematical model, where mechanical regulation of BMP-2 production mediates rates of cellular proliferation, differentiation and tissue production, to predict healing outcomes. A parametric approach enables the spatial and temporal prediction of endochondral tissue regeneration, assessed as areas of cartilage and mineralized bone, as functions of radial distance from the periosteum and time. Comparing model results to histological outcomes from two previous studies of periosteum-mediated bone regeneration in a common ovine model, it was shown that mechanistic models incorporating mechanical feedback successfully predict patterns (spatial) and trends (temporal) of bone tissue regeneration. The novel model framework presented here integrates a mechanistic feedback system based on the

  18. TUNE FEEDBACK AT RHIC

    SciTech Connect

    CAMERON,P.; CERNIGLIA,P.; CONNOLLY,R.; CUPOLO,J.; DAWSON,W.C.; DEGEN,C.; DELLAPENNA,A.; DELONG,J.; DREES,A.; HUHN,A.; KESSELMAN,M.; MARUSIC,A.; OERTER,B.; MEAD,J.; SCHULTHEISS,C.; SIKORA,R.; VAN ZEIJTS,J.

    2001-06-18

    Preliminary phase-locked loop betatron tune measurement results were obtained during RHIC 2000 with a resonant Beam Position Monitor. These results suggested the possibility of incorporating PLL tune measurement into a tune feedback system for RHIC 2001. Tune feedback is useful in a superconducting accelerator, where the machine cycle time is long and inefficient acceleration due to resonance crossing is not comfortably tolerated. This is particularly true with the higher beam intensities planned for RHIC 2001. We present descriptions of a PLL tune measurement system implemented in the DSP/FPGA environment of a RHIC BPM electronics module and the feedback system into which the measurement is incorporated to regulate tune. In addition, we present results from the commissioning of this system during RHIC 2001.

  19. Molecular Gas Heating Mechanisms, and Star Formation Feedback in Merger/Starbursts: NGC 6240 and Arp 193 as Case Studies

    NASA Astrophysics Data System (ADS)

    Papadopoulos, Padelis P.; Zhang, Zhi-Yu; Xilouris, E. M.; Weiss, Axel; van der Werf, Paul; Israel, F. P.; Greve, T. R.; Isaak, Kate G.; Gao, Y.

    2014-06-01

    We used the SPIRE/FTS instrument aboard the Herschel Space Observatory to obtain the Spectral Line Energy Distributions (SLEDs) of CO from J = 4-3 to J = 13-12 of Arp 193 and NGC 6240, two classical merger/starbursts selected from our molecular line survey of local Luminous Infrared Galaxies (L IR >= 1011 L ⊙). The high-J CO SLEDs are then combined with ground-based low-J CO, 13CO, HCN, HCO+, CS line data and used to probe the thermal and dynamical states of their large molecular gas reservoirs. We find the two CO SLEDs strongly diverging from J = 4-3 onward, with NGC 6240 having a much higher CO line excitation than Arp 193, despite their similar low-J CO SLEDs and L FIR/L CO, 1 - 0, L HCN/L CO (J = 1-0) ratios (proxies of star formation efficiency and dense gas mass fraction). In Arp 193, one of the three most extreme starbursts in the local universe, the molecular SLEDs indicate a small amount (~5%-15%) of dense gas (n >= 104 cm-3) unlike NGC 6240 where most of the molecular gas (~60%-70%) is dense (n ~ (104-105) cm-3). Strong star-formation feedback can drive this disparity in their dense gas mass fractions, and also induce extreme thermal and dynamical states for the molecular gas. In NGC 6240, and to a lesser degree in Arp 193, we find large molecular gas masses whose thermal states cannot be maintained by FUV photons from Photon-Dominated Regions. We argue that this may happen often in metal-rich merger/starbursts, strongly altering the initial conditions of star formation. ALMA can now directly probe these conditions across cosmic epoch, and even probe their deeply dust-enshrouded outcome, the stellar initial mass function averaged over galactic evolution.

  20. Steroid induction of therapy-resistant cytokeratin-5-positive cells in estrogen receptor-positive breast cancer through a BCL6-dependent mechanism.

    PubMed

    Goodman, C R; Sato, T; Peck, A R; Girondo, M A; Yang, N; Liu, C; Yanac, A F; Kovatich, A J; Hooke, J A; Shriver, C D; Mitchell, E P; Hyslop, T; Rui, H

    2016-03-17

    Therapy resistance remains a major problem in estrogen receptor-α (ERα)-positive breast cancer. A subgroup of ERα-positive breast cancer is characterized by mosaic presence of a minor population of ERα-negative cancer cells expressing the basal cytokeratin-5 (CK5). These CK5-positive cells are therapy resistant and have increased tumor-initiating potential. Although a series of reports document induction of the CK5-positive cells by progestins, it is unknown if other 3-ketosteroids share this ability. We now report that glucocorticoids and mineralocorticoids effectively expand the CK5-positive cell population. CK5-positive cells induced by 3-ketosteroids lacked ERα and progesterone receptors, expressed stem cell marker, CD44, and displayed increased clonogenicity in soft agar and broad drug-resistance in vitro and in vivo. Upregulation of CK5-positive cells by 3-ketosteroids required induction of the transcriptional repressor BCL6 based on suppression of BCL6 by two independent BCL6 small hairpin RNAs or by prolactin. Prolactin also suppressed 3-ketosteroid induction of CK5+ cells in T47D xenografts in vivo. Survival analysis with recursive partitioning in node-negative ERα-positive breast cancer using quantitative CK5 and BCL6 mRNA or protein expression data identified patients at high or low risk for tumor recurrence in two independent patient cohorts. The data provide a mechanism by which common pathophysiological or pharmacologic elevations in glucocorticoids or other 3-ketosteroids may adversely affect patients with mixed ERα+/CK5+ breast cancer. The observations further suggest a cooperative diagnostic utility of CK5 and BCL6 expression levels and justify exploring efficacy of inhibitors of BCL6 and 3-ketosteroid receptors for a subset of ERα-positive breast cancers. PMID:26096934

  1. Development of a Magneto-Resistive Angular Position Sensor for Space Mechanisms

    NASA Technical Reports Server (NTRS)

    Hahn, Robert; Schmidt, Tilo; Seifart, Klaus; Olberts, Bastian; Romera, Fernando

    2016-01-01

    Magnetic microsystems in the form of magneto-resistive (MR) sensors are firmly established in automobiles and industrial applications. They are used to measure travel, angle, electrical current, or magnetic fields. MR technology opens up new sensor possibilities in space applications and can be an enabling technology for optimal performance, high robustness and long lifetime at reasonable costs. In some science missions, the technology is already applied, however, the designs are proprietary and case specific, for instance in case of the angular sensors used for JPL/NASA's Mars rover Curiosity [1]. Since 2013 HTS GmbH and Sensitec GmbH have teamed up to develop and qualify a standardized yet flexible to use MR angular sensor for space mechanisms. Starting with a first assessment study and market survey performed under ESA contract, a very strong industry interest in novel, contactless position measurement means was found. Currently a detailed and comprehensive development program is being performed by HTS and Sensitec. The objective of this program is to advance the sensor design up to Engineering Qualification Model level and to perform qualification testing for a representative space application. The paper briefly reviews the basics of magneto-resistive effects and possible sensor applications and describes the key benefits of MR angular sensors with reference to currently operational industrial and space applications. The key applications and specification are presented and the preliminary baseline mechanical and electrical design will be discussed. An outlook on the upcoming development and test stages as well as the qualification program will be provided.

  2. The Art of Giving Online Feedback

    ERIC Educational Resources Information Center

    Leibold, Nancyruth; Schwarz, Laura Marie

    2015-01-01

    The cultivation of providing online feedback that is positive, effective, and enhances the learning experience is a valuable educator skill. Acquisition of the art of providing feedback is through education, practice, and faculty development. This article provides information about the best practices for delivering online feedback to learners. An…

  3. Diabetic complications within the context of aging: Nicotinamide adenine dinucleotide redox, insulin C-peptide, sirtuin 1-liver kinase B1-adenosine monophosphate-activated protein kinase positive feedback and forkhead box O3.

    PubMed

    Ido, Yasuo

    2016-07-01

    Recent research in nutritional control of aging suggests that cytosolic increases in the reduced form of nicotinamide adenine dinucleotide and decreasing nicotinamide adenine dinucleotide metabolism plays a central role in controlling the longevity gene products sirtuin 1 (SIRT1), adenosine monophosphate-activated protein kinase (AMPK) and forkhead box O3 (FOXO3). High nutrition conditions, such as the diabetic milieu, increase the ratio of reduced to oxidized forms of cytosolic nicotinamide adenine dinucleotide through cascades including th