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Sample records for vibratory signals derive

  1. Interference of Overlapping Insect Vibratory Communication Signals: An Eushistus heros Model.

    Directory of Open Access Journals (Sweden)

    Andrej Čokl

    Full Text Available Plants limit the range of insect substrate-borne vibratory communication by their architecture and mechanical properties that change transmitted signal time, amplitude and frequency characteristics. Stinkbugs gain higher signal-to-noise ratio and increase communication distance by emitting narrowband low frequency vibratory signals that are tuned with transmission properties of plants. The objective of the present study was to investigate hitherto overlooked consequences of duetting with mutually overlapped narrowband vibratory signals. The overlapped vibrations of the model stinkbug species Eushistus heros, produced naturally or induced artificially on different plants, have been analysed. They represent female and male strategies to preserve information within a complex masked signal. The brown stinkbugs E. heros communicate with species and gender specific vibratory signals that constitute characteristic duets in the calling, courtship and rivalry phases of mating behaviour. The calling female pulse overlaps the male vibratory response when the latency of the latter is shorter than the duration of the female triggering signal or when the male response does not inhibit the following female pulse. Overlapping of signals induces interference that changes their amplitude pattern to a sequence of regularly repeated pulses in which their duration and the difference between frequencies of overlapped vibrations are related inversely. Interference does not occur in overlapped narrow band female calling pulses and broadband male courtship pulse trains. In a duet with overlapped signals females and males change time parameters and increase the frequency difference between signals by changing the frequency level and frequency modulation pattern of their calls.

  2. Genetics Home Reference: vibratory urticaria

    Science.gov (United States)

    ... Facebook Twitter Home Health Conditions vibratory urticaria vibratory urticaria Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Vibratory urticaria is a condition in which exposing the skin ...

  3. Coriolis vibratory gyroscopes theory and design

    CERN Document Server

    Apostolyuk, Vladislav

    2016-01-01

    This book provides the latest theoretical analysis and design methodologies of different types of Coriolis vibratory gyroscopes (CVG). Together, the chapters analyze different types of sensitive element designs and their kinematics, derivation of motion equations, analysis of sensitive elements dynamics in modulated and demodulated signals, calculation and optimization of main performance characteristics, and signal processing and control. Essential aspects of numerical simulation of CVG using Simulink® are also covered. This is an ideal book for graduate students, researchers, and engineers working in fields that require gyroscope application, including but not limited to: inertial sensors and systems, automotive and consumer electronics, small unmanned aircraft control systems, personal mobile navigation systems and related software development, and augmented and virtual reality systems.

  4. Characterization of the Bell-Shaped Vibratory Angular Rate Gyro

    Directory of Open Access Journals (Sweden)

    Junfang Fan

    2013-08-01

    Full Text Available The bell-shaped vibratory angular rate gyro (abbreviated as BVG is a novel shell vibratory gyroscope, which is inspired by the Chinese traditional bell. It sensitizes angular velocity through the standing wave precession effect. The bell-shaped resonator is a core component of the BVG and looks like the millimeter-grade Chinese traditional bell, such as QianLong Bell and Yongle Bell. It is made of Ni43CrTi, which is a constant modulus alloy. The exciting element, control element and detection element are uniformly distributed and attached to the resonator, respectively. This work presents the design, analysis and experimentation on the BVG. It is most important to analyze the vibratory character of the bell-shaped resonator. The strain equation, internal force and the resonator's equilibrium differential equation are derived in the orthogonal curvilinear coordinate system. When the input angular velocity is existent on the sensitive axis, an analysis of the vibratory character is performed using the theory of thin shells. On this basis, the mode shape function and the simplified second order normal vibration mode dynamical equation are obtained. The coriolis coupling relationship about the primary mode and secondary mode is established. The methods of the signal processing and control loop are presented. Analyzing the impact resistance property of the bell-shaped resonator, which is compared with other shell resonators using the Finite Element Method, demonstrates that BVG has the advantage of a better impact resistance property. A reasonable means of installation and a prototypal gyro are designed. The gyroscopic effect of the BVG is characterized through experiments. Experimental results show that the BVG has not only the advantages of low cost, low power, long work life, high sensitivity, and so on, but, also, of a simple structure and a better impact resistance property for low and medium angular velocity measurements.

  5. Acoustic-Frequency Vibratory Stimulation Regulates the Balance between Osteogenesis and Adipogenesis of Human Bone Marrow-Derived Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Xi Chen

    2015-01-01

    Full Text Available Osteoporosis can be associated with the disordered balance between osteogenesis and adipogenesis of bone marrow-derived mesenchymal stem cells (BM-MSCs. Although low-frequency mechanical vibration has been demonstrated to promote osteogenesis, little is known about the influence of acoustic-frequency vibratory stimulation (AFVS. BM-MSCs were subjected to AFVS at frequencies of 0, 30, 400, and 800 Hz and induced toward osteogenic or adipogenic-specific lineage. Extracellular matrix mineralization was determined by Alizarin Red S staining and lipid accumulation was assessed by Oil Red O staining. Transcript levels of osteogenic and adipogenic marker genes were evaluated by real-time reverse transcription-polymerase chain reaction. Cell proliferation of BM-MSCs was promoted following exposure to AFVS at 800 Hz. Vibration at 800 Hz induced the highest level of calcium deposition and significantly increased mRNA expression of COL1A1, ALP, RUNX2, and SPP1. The 800 Hz group downregulated lipid accumulation and levels of adipogenic genes, including FABP4, CEBPA, PPARG, and LEP, while vibration at 30 Hz supported adipogenesis. BM-MSCs showed a frequency-dependent response to acoustic vibration. AFVS at 800 Hz was the most favorable for osteogenic differentiation and simultaneously suppressed adipogenesis. Thus, acoustic vibration could potentially become a novel means to prevent and treat osteoporosis.

  6. A vibratory micromechanical gyroscope

    Science.gov (United States)

    Boxenhorn, Burton; Greiff, Paul

    A novel vibratory micromechanical gyro with an active area less than one millimeter square has been analyzed, designed, and built. It has been demonstrated that such a gyro can be built using semiconductor fabrication techniques, and that the resulting performance is reasonably predictable. Further improvement of this gyro will result in an instrument that is small, low power, and in particular, will be very cheap in large quantitites.

  7. Silicon Bulk Micromachined Vibratory Gyroscope

    Science.gov (United States)

    Tang, T. K.; Gutierrez, R. C.; Wilcox, J. Z.; Stell, C.; Vorperian, V.; Calvet, R.; Li, W. J.; Charkaborty, I.; Bartman, R.; Kaiser, W. J.

    1996-01-01

    This paper reports on design, modeling, fabrication, and characterization of a novel silicon bulk micromachined vibratory rate gyroscope designed for microspacecraft applications. The new microgyroscope consists of a silicon four leaf cloverstructure with a post attached to the center.

  8. Mechanical and Electrical Noise in Sense Channel of MEMS Vibratory Gyroscopes.

    Science.gov (United States)

    Ding, Xukai; Jia, Jia; Gao, Yang; Li, Hongsheng

    2017-10-11

    This paper presents a theoretical analysis of mechanical and electrical noise in the sense channel of micro-electromechanical systems (MEMS) vibratory gyroscopes. Closed-form expressions for the power spectral density (PSD) of the noise equivalent rate (NER) of gyroscopes in the open-loop and the force-rebalance operations are derived by using an averaged PSD model and an equivalent transfer function. The obtained expressions are verified through numerical simulations, demonstrating close agreements between the analytic and the numerical models. Based on the derived expressions for the PSD of the NER, the impacts of the modal frequency split, quality factor, and the gain of the feedback forcer, as well as the gain of the signal conditioning circuit, on the gyroscope noise characteristics are theoretically analyzed. In addition, the angle random walk (ARW) and the standard deviation of the NER are also discussed through the PSD models. Finally, the effects of the loop closing, the mode matching, and the gain of the feedback forcer on the PSD of the NER were verified via a MEMS vibratory gyroscope with a tunable modal frequency split.

  9. Error Model and Compensation of Bell-Shaped Vibratory Gyro

    OpenAIRE

    Zhong Su; Ning Liu; Qing Li

    2015-01-01

    A bell-shaped vibratory angular velocity gyro (BVG), inspired by the Chinese traditional bell, is a type of axisymmetric shell resonator gyroscope. This paper focuses on development of an error model and compensation of the BVG. A dynamic equation is firstly established, based on a study of the BVG working mechanism. This equation is then used to evaluate the relationship between the angular rate output signal and bell-shaped resonator character, analyze the influence of the main error source...

  10. GEC Ferranti piezo vibratory gyroscope

    Science.gov (United States)

    Nuttall, J. D.

    1993-01-01

    Prototypes of a piezo-electric vibratory angular rate transducer (gyroscope) (PVG) have been constructed and evaluated. The construction is on the lines suggested by Burdess. The sensitive element is a cylinder of radially poled piezo-electric ceramic. The cylinder is metallized inside and out, and the outer metallization is divided into eight electrodes. The metallization on the inside is earthed. A phase locked loop, using pairs of the electrodes, causes the cylinder to vibrate in one of its two fundamental, degenerate modes. In the presence of rotation, some of the vibration is coupled into the outer mode. This can be detected, or suppressed with a closed-up technique and provides a measure of rotation rate. The gyroscope provides a number of advantages over rotating mass and optical instruments: low size and mass, lower power consumption, potentially high reliability, potentially good dormancy, low cost and high maximum rate.

  11. Reproductive Biology, Mating Behavior, and Vibratory Communication of the Brown-Winged Stink Bug, Edessa meditabunda (Fabr. (Heteroptera: Pentatomidae

    Directory of Open Access Journals (Sweden)

    Cleonor Cavalcante A. Silva

    2012-01-01

    Full Text Available We describe different aspects of the reproductive biology, mating behavior, and vibratory communication of the pentatomid Edessa meditabunda (Fabr.. This species shows lower copulation frequency and reproductive potential with longer sexual maturation period compared to other species of pentatomids. Females with multiple mating show increased fecundity when compared with single-mated females and both increased fecundity and reduced longevity when compared with virgin females. Courtship and mating behavior and vibratory signals are typical and similar to what was observed in other species of pentatomids, except that males started the courtship. These results constitute the first paper on biology, behavior, and vibratory communication among species of the subfamily Edessinae.

  12. A novel oscillation control for MEMS vibratory gyroscopes using a modified electromechanical amplitude modulation technique

    Science.gov (United States)

    Ma, Wei; Lin, Yiyu; Liu, Siqi; Zheng, Xudong; Jin, Zhonghe

    2017-02-01

    This paper reports a novel oscillation control algorithm for MEMS vibratory gyroscopes using a modified electromechanical amplitude modulation (MEAM) technique, which enhances the robustness against the frequency variation of the driving mode, compared to the conventional EAM (CEAM) scheme. In this approach, the carrier voltage exerted on the proof mass is frequency-modulated by the drive resonant frequency. Accordingly, the pick-up signal from the interface circuit involves a constant-frequency component that contains the amplitude and phase information of the vibration displacement. In other words, this informational detection signal is independent of the mechanical resonant frequency, which varies due to different batches, imprecise micro-fabrication and changing environmental temperature. In this paper, the automatic gain control loop together with the phase-locked loop are simultaneously analyzed using the averaging method and Routh-Hurwitz criterion, deriving the stability condition and the parameter optimization rules of the transient response. Then, a simulation model based on the real system is set up to evaluate the control algorithm. Further, the proposed MEAM method is tested using a field-programmable-gate-array based digital platform on a capacitive vibratory gyroscope. By optimizing the control parameters, the transient response of the drive amplitude reveals a settling time of 45.2 ms without overshoot, according well with the theoretical prediction and simulation results. The first measurement results show that the amplitude variance of the drive displacement is 12 ppm in an hour while the phase standard deviation is as low as 0.0004°. The mode-split gyroscope operating under atmospheric pressure demonstrates an outstanding performance. By virtue of the proposed MEAM method, the bias instability and angle random walk are measured to be 0.9° h-1 (improved by 2.4 times compared to the CEAM method) and 0.068° (√h)-1 (improved by 1.4 times

  13. Agrobacterium tumefaciens responses to plant-derived signaling molecules

    Science.gov (United States)

    Subramoni, Sujatha; Nathoo, Naeem; Klimov, Eugene; Yuan, Ze-Chun

    2014-01-01

    As a special phytopathogen, Agrobacterium tumefaciens infects a wide range of plant hosts and causes plant tumors also known as crown galls. The complexity of Agrobacterium–plant interaction has been studied for several decades. Agrobacterium pathogenicity is largely attributed to its evolved capabilities of precise recognition and response to plant-derived chemical signals. Agrobacterium perceives plant-derived signals to activate its virulence genes, which are responsible for transferring and integrating its Transferred DNA (T-DNA) from its Tumor-inducing (Ti) plasmid into the plant nucleus. The expression of T-DNA in plant hosts leads to the production of a large amount of indole-3-acetic acid (IAA), cytokinin (CK), and opines. IAA and CK stimulate plant growth, resulting in tumor formation. Agrobacterium utilizes opines as nutrient sources as well as signals in order to activate its quorum sensing (QS) to further promote virulence and opine metabolism. Intriguingly, Agrobacterium also recognizes plant-derived signals including γ-amino butyric acid and salicylic acid (SA) to activate quorum quenching that reduces the level of QS signals, thereby avoiding the elicitation of plant defense and preserving energy. In addition, Agrobacterium hijacks plant-derived signals including SA, IAA, and ethylene to down-regulate its virulence genes located on the Ti plasmid. Moreover, certain metabolites from corn (Zea mays) also inhibit the expression of Agrobacterium virulence genes. Here we outline the responses of Agrobacterium to major plant-derived signals that impact Agrobacterium–plant interactions. PMID:25071805

  14. Agrobacterium tumefaciens responses to plant-derived signaling molecules

    Directory of Open Access Journals (Sweden)

    Sujatha eSubramoni

    2014-07-01

    Full Text Available As a special phytopathogen, Agrobacterium tumefaciens infects a wide range of plant hosts and causes plant tumors also known as crown galls. The complexity of Agrobacterium-plant interaction has been studied for several decades. Agrobacterium pathogenicity is largely attributed to its evolved capabilities of precise recognition and response to plant-derived chemical signals. Agrobacterium perceives plant-derived signals to activate its virulence genes, which are responsible for transferring and integrating its T-DNA (Transferred DNA from its Tumour-inducing (Ti plasmid into the plant nucleus. The expression of T-DNA in plant hosts leads to the production of a large amount of indole-3-acetic acid (IAA, cytokinin (CK and opines. IAA and CK stimulate plant growth, resulting in tumor formation. Agrobacterium utilizes opines as nutrient sources as well as signals in order to activate its quorum sensing (QS to further promote virulence and opine metabolism. Intriguingly, Agrobacterium also recognizes plant-derived signals including -amino butyric acid (GABA and salicylic acid (SA to activate quorum quenching that reduces the level of QS signals, thereby avoiding the elicitation of plant defense and preserving energy. In addition, Agrobacterium hijacks plant-derived signals including SA, IAA, and ethylene (ET to down-regulate its virulence genes located on the Ti plasmid. Moreover, certain metabolites from corn (Zea mays also inhibit the expression of Agrobacterium virulence genes. Here we outline the responses of Agrobacterium to major plant-derived signals that impact Agrobacterium-plant interactions.

  15. Using detrended fluctuation analysis (DFA) to analyze whether vibratory insoles enhance balance stability for elderly fallers.

    Science.gov (United States)

    Wang, Chien-Chih; Yang, Wen-Hung

    2012-01-01

    Falls are a common and devastating problem among elderly people. In a previous study, vibratory insoles were developed to improve postural stability for elderly fallers. To verify the effects of vibratory insoles, a two-stage experiment was conducted to collect center of pressure (COP) signals from 26 elderly fallers and 16 healthy young subjects while standing still. The DFA is used to analyze the behavior of different time-series data obtained from the trajectory of COP. Postural stability was compared by the DFA scaling exponent between a control condition (before using vibratory insoles) and a vibration condition (after using vibratory insoles). For elderly fallers, DFA scaling exponents 95% confidence interval were [1.434, 1.547] and [1.329, 1.451] under control and vibration conditions in the anteroposterior (AP) direction, respectively. The experimental results revealed that temporary stimuli of appropriate amplitude produced by vibration insoles enhanced postural stability in elderly fallers and was more obvious in the AP direction. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  16. Parametrically disciplined operation of a vibratory gyroscope

    Science.gov (United States)

    Shcheglov, Kirill V. (Inventor); Hayworth, Ken J. (Inventor); Challoner, A. Dorian (Inventor); Peay, Chris S. (Inventor)

    2008-01-01

    Parametrically disciplined operation of a symmetric nearly degenerate mode vibratory gyroscope is disclosed. A parametrically-disciplined inertial wave gyroscope having a natural oscillation frequency in the neighborhood of a sub-harmonic of an external stable clock reference is produced by driving an electrostatic bias electrode at approximately twice this sub-harmonic frequency to achieve disciplined frequency and phase operation of the resonator. A nearly symmetric parametrically-disciplined inertial wave gyroscope that can oscillate in any transverse direction and has more than one bias electrostatic electrode that can be independently driven at twice its oscillation frequency at an amplitude and phase that disciplines its damping to zero in any vibration direction. In addition, operation of a parametrically-disciplined inertial wave gyroscope is taught in which the precession rate of the driven vibration pattern is digitally disciplined to a prescribed non-zero reference value.

  17. Error Model and Compensation of Bell-Shaped Vibratory Gyro.

    Science.gov (United States)

    Su, Zhong; Liu, Ning; Li, Qing

    2015-09-17

    A bell-shaped vibratory angular velocity gyro (BVG), inspired by the Chinese traditional bell, is a type of axisymmetric shell resonator gyroscope. This paper focuses on development of an error model and compensation of the BVG. A dynamic equation is firstly established, based on a study of the BVG working mechanism. This equation is then used to evaluate the relationship between the angular rate output signal and bell-shaped resonator character, analyze the influence of the main error sources and set up an error model for the BVG. The error sources are classified from the error propagation characteristics, and the compensation method is presented based on the error model. Finally, using the error model and compensation method, the BVG is calibrated experimentally including rough compensation, temperature and bias compensation, scale factor compensation and noise filter. The experimentally obtained bias instability is from 20.5°/h to 4.7°/h, the random walk is from 2.8°/h(1/2) to 0.7°/h(1/2) and the nonlinearity is from 0.2% to 0.03%. Based on the error compensation, it is shown that there is a good linear relationship between the sensing signal and the angular velocity, suggesting that the BVG is a good candidate for the field of low and medium rotational speed measurement.

  18. Modification of piezoelectric vibratory gyroscope resonator parameters by feedback control

    CSIR Research Space (South Africa)

    Loveday, PW

    1998-09-01

    Full Text Available A method for analyzing the effect of feedback control on the dynamics of piezoelectric resonators used in vibratory gyroscopes has been developed. This method can be used to determine the feasibility of replacing the traditional mechanical balancing...

  19. Vibratory gyroscopes : identification of mathematical model from test data

    CSIR Research Space (South Africa)

    Shatalov, MY

    2007-05-01

    Full Text Available Simple mathematical model of vibratory gyroscopes imperfections is formulated, which includes anisotropic damping and variation of mass-stiffness parameters and their harmonics. The method of identification of parameters of the mathematical model...

  20. Configuration System for Simulation Based Design of Vibratory Bowl Feeders

    DEFF Research Database (Denmark)

    Hansson, Michael Natapon; Mathiesen, Simon; Ellekilde, Lars-Peter

    2017-01-01

    Vibratory bowl feeders are still among the most commonly used production equipment for automated part feeding, where parts are correctly oriented for further manipulation by being conveyed through a set of orienting devices. Designing vibratory bowl feeders involves selecting and sequencing a num...... the configuration task. To test the approach, the configuration system is used to find three device sequences for feeding three parts in specific orientations. The sequences are validated through simulation and real world experiments, showing good consistency....

  1. Optimization of vibratory welding process parameters using response surface methodology

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Pravin Kumar; Kumar, S. Deepak; Patel, D.; Prasad, S. B. [National Institute of Technology Jamshedpur, Jharkhand (India)

    2017-05-15

    The current investigation was carried out to study the effect of vibratory welding technique on mechanical properties of 6 mm thick butt welded mild steel plates. A new concept of vibratory welding technique has been designed and developed which is capable to transfer vibrations, having resonance frequency of 300 Hz, into the molten weld pool before it solidifies during the Shielded metal arc welding (SMAW) process. The important process parameters of vibratory welding technique namely welding current, welding speed and frequency of the vibrations induced in molten weld pool were optimized using Taguchi’s analysis and Response surface methodology (RSM). The effect of process parameters on tensile strength and hardness were evaluated using optimization techniques. Applying RSM, the effect of vibratory welding parameters on tensile strength and hardness were obtained through two separate regression equations. Results showed that, the most influencing factor for the desired tensile strength and hardness is frequency at its resonance value, i.e. 300 Hz. The micro-hardness and microstructures of the vibratory welded joints were studied in detail and compared with those of conventional SMAW joints. Comparatively, uniform and fine grain structure has been found in vibratory welded joints.

  2. NT2 derived neuronal and astrocytic network signalling.

    Directory of Open Access Journals (Sweden)

    Eric J Hill

    Full Text Available A major focus of stem cell research is the generation of neurons that may then be implanted to treat neurodegenerative diseases. However, a picture is emerging where astrocytes are partners to neurons in sustaining and modulating brain function. We therefore investigated the functional properties of NT2 derived astrocytes and neurons using electrophysiological and calcium imaging approaches. NT2 neurons (NT2Ns expressed sodium dependent action potentials, as well as responses to depolarisation and the neurotransmitter glutamate. NT2Ns exhibited spontaneous and coordinated calcium elevations in clusters and in extended processes, indicating local and long distance signalling. Tetrodotoxin sensitive network activity could also be evoked by electrical stimulation. Similarly, NT2 astrocytes (NT2As exhibited morphology and functional properties consistent with this glial cell type. NT2As responded to neuronal activity and to exogenously applied neurotransmitters with calcium elevations, and in contrast to neurons, also exhibited spontaneous rhythmic calcium oscillations. NT2As also generated propagating calcium waves that were gap junction and purinergic signalling dependent. Our results show that NT2 derived astrocytes exhibit appropriate functionality and that NT2N networks interact with NT2A networks in co-culture. These findings underline the utility of such cultures to investigate human brain cell type signalling under controlled conditions. Furthermore, since stem cell derived neuron function and survival is of great importance therapeutically, our findings suggest that the presence of complementary astrocytes may be valuable in supporting stem cell derived neuronal networks. Indeed, this also supports the intriguing possibility of selective therapeutic replacement of astrocytes in diseases where these cells are either lost or lose functionality.

  3. Effects of ejaculation by penile vibratory stimulation on bladder capacity in men with spinal cord lesions

    DEFF Research Database (Denmark)

    Laessøe, Line; Sønksen, Jens; Bagi, Per

    2003-01-01

    We examined the effects of ejaculation by penile vibratory stimulation on bladder capacity in men with spinal cord lesions.......We examined the effects of ejaculation by penile vibratory stimulation on bladder capacity in men with spinal cord lesions....

  4. A subharmonic vibratory pattern in normal vocal folds

    NARCIS (Netherlands)

    Svec, JG; Schutte, HK; Miller, DG

    This study observes in detail an F-0/2 (sounding an octave below an original tone) subharmonic vibratory pattern produced in a normal larynx. Simultaneous electroglottographic and photoglottographic measurements reveal two different open phases within a subharmonic cycle-the first shorter with a

  5. Automation Selection and Sequencing of Traps for Vibratory Feeders

    DEFF Research Database (Denmark)

    Mathiesen, Simon; Ellekilde, Lars-Peter

    2017-01-01

    Vibratory parts feeders with mechanical orienting devices are used extensively in the assembly automation industry. Even so, the design process is based on trial-and-error approaches and is largely manual. In this paper, a methodology is presented for automatic design of this type of feeder...

  6. Regulation of tissue morphogenesis by endothelial cell-derived signals

    Science.gov (United States)

    Ramasamy, Saravana K.; Kusumbe, Anjali P.; Adams, Ralf H.

    2016-01-01

    Summary Endothelial cells form an extensive network of blood vessels that has numerous essential functions in the vertebrate body. In addition to their well-established role as a versatile transport network, blood vessels can induce organ formation or direct growth and differentiation processes by providing signals in a paracrine (angiocrine) fashion. Tissue repair also requires the local restoration of vasculature. Endothelial cells are emerging as important signaling centers that coordinate regeneration and help to prevent deregulated, disease-promoting processes. Vascular cells are also part of stem cell niches and play key roles in hematopoiesis, bone formation and neurogenesis. Here, we will review these newly identified roles of endothelial cells in the regulation of organ morphogenesis, maintenance and regeneration. PMID:25529933

  7. The dynamics of cavity clusters in ultrasonic (vibratory) cavitation erosion

    DEFF Research Database (Denmark)

    Hansson, I.; Mørch, Knud Aage

    1980-01-01

    The erosion of solids caused by cavitating liquids is a result of the concerted collapse of clusters of cavities. In vibratory cavitation equipment the clusters grow and collapse adjacent to a solid surface and are typically of hemispherical or cylindrical form. In the present paper the collapse...... process of these clusters is described and the collapse equations are developed and solved. The theoretical results are compared with results from high-speed photography of the clusters and with the initial stages of cavitation erosion on metal specimens. Experimental and theoretical results show...

  8. Used Furan Sand Reclamation in REGMAS Vibratory Unit

    Directory of Open Access Journals (Sweden)

    Dańko J.

    2015-09-01

    Full Text Available The paper, especially dealt with problems of reclamation of used furan sand, carried out in new, vibratory sand reclamation unit REGMAS developed by researches from AGH-University of Science and Technology, Faculty of Foundry Engineering in Cracow (Poland. Functional characteristics of reclamation unit as well as the results of reclamation of used sand with furfuryl resin are discussed in the paper. The quality of reclaim was tested by means of the LOI and pH value, dust content in the reclaim and at least by the the quality of the castings produced in moulds prepared with the use of reclaimed matrix.

  9. Quorum sensing signalling and biofilm formation of brewery-derived bacteria, and inhibition of signalling by natural compounds.

    Science.gov (United States)

    Priha, O; Virkajärvi, V; Juvonen, R; Puupponen-Pimiä, R; Nohynek, L; Alakurtti, S; Pirttimaa, M; Storgårds, E

    2014-11-01

    Bacteria use quorum sensing signalling in various functions, e.g. while forming biofilms, and inhibition of this signalling could be one way to control biofilm formation. The aim of this study was to evaluate the production of signalling molecules and its correlation with the biofilm formation capability of bacteria isolated from brewery filling process. A further aim was to study berry extracts and wood-derived terpenes for their possible quorum sensing inhibitory effects. Out of the twenty bacteria studied, five produced short-chain and five long-chain AHL (acyl homoserine lactone) signalling molecules when tested with the Chromobacterium violaceum CV026 reporter bacterium. Production of AI-2 (autoinducer-2) signalling molecules was detected from nine strains with the Vibrio harveyi BB170 bioassay. Over half of the strains produced biofilm in the microtitre plate assay, but the production of AHL and AI-2 signalling molecules and biofilm formation capability did not directly correlate with each other. Out of the 13 berry extracts and wood-derived terpenes screened, four compounds decreased AHL signalling without effect on growth. These were betulin, raspberry extract and two cloudberry extracts. The effect of these compounds on biofilm formation of the selected six bacterial strains varied. The phenolic extract of freeze-dried cloudberry fruit caused a statistically significant reduction of biofilm formation of Obesumbacterium proteus strain. Further experiments should aim at identifying the active compounds and revealing whether quorum sensing inhibition causes structural changes in the biofilms formed.

  10. Field Tests to Investigate the Penetration Rate of Piles Driven by Vibratory Installation

    Directory of Open Access Journals (Sweden)

    Zhaohui Qin

    2017-01-01

    Full Text Available Factors directly affecting the penetration rate of piles installed by vibratory driving technique are summarized and classified into seven aspects which are driving force, resistance, vibratory amplitude, energy consumption, speeding up at the beginning, pile plumbness keeping, and slowing down at the end, from the mechanism and engineering practice of the vibratory pile driving. In order to find out how these factors affect the penetration rate of the pile in three major actors of vibratory pile driving: (i the pile to be driven, (ii the selected driving system, and (iii the imposed soil conditions, field tests on steel sheet piles driven by vibratory driving technique in different soil conditions are conducted. The penetration rates of three different sheet pile types having up to four different lengths installed using two different vibratory driving systems are documented. Piles with different lengths and types driven with or without clutch have different penetration rates. The working parameters of vibratory hammer, such as driving force and vibratory amplitude, have great influences on the penetration rate of the pile, especially at the later stages of the sinking process. Penetration rate of piles driven in different soil conditions is uniform because of the different penetration resistance including shaft friction and toe resistance.

  11. Derivation of the respiratory rate from directly and indirectly measured respiratory signals using autocorrelation

    Directory of Open Access Journals (Sweden)

    Schrumpf Fabian

    2016-09-01

    Full Text Available The estimation of respiratory rates from contineous respiratory signals is commonly done using either fourier transformation or the zero-crossing method. This paper introduces another method which is based on the autocorrelation function of the respiratory signal. The respiratory signals can be measured either directly using a flow sensor or chest strap or indirectly on the basis of the electrocardiogram (ECG. We compare our method against other established methods on the basis of real-world ECG signals and use a respiration-based breathing frequency as a reference. Our method achieved the best agreement between respiration rates derived from directly and indirectly measured respiratory signals.

  12. A high-efficiency self-powered wireless sensor node for monitoring concerning vibratory events

    Science.gov (United States)

    Xu, Dacheng; Li, Suiqiong; Li, Mengyang; Xie, Danpeng; Dong, Chuan; Li, Xinxin

    2017-09-01

    This paper presents a self-powered wireless alarming sensor node (SWASN), which was designed to monitor the occurrence of concerning vibratory events. The major components of the sensor node include a vibration-threshold-triggered energy harvester (VTTEH) that powers the sensor node, a dual threshold voltage control circuit (DTVCC) for power management and a radio frequency (RF) signal transmitting module. The VTTEH generates significant electric energy only when the input vibration reaches certain amplitude. Thus, the VTTEH serves as both the power source and the vibration-event-sensing element for the sensor node. The DTVCC was specifically designed to utilize the limited power supply from the VTTEH to operate the sensor node. Constructed with only voltage detectors and MOSFETs, the DTVCC achieved low power consumption, which was 65% lower compared with the power management circuit designed in our previous work. Meanwhile, a RF transmit circuit was constructed based on the commercially available CC1110-F32 wireless transceiver chip and a compact planar antenna was designed to improve the signal transmission distance. The sensor node was fabricated and was characterized both in the laboratory and in the field. Experimental results showed that the SWASN could automatically send out alarming signals when the simulated concerning event occurred. The waiting time between two consecutive transmission periods is less than 125 s and the transmission distance can reach 1.31 km. The SWASN will have broad applications in field surveillances.

  13. Adaptive Control of a Vibratory Angle Measuring Gyroscope

    Science.gov (United States)

    Park, Sungsu

    2010-01-01

    This paper presents an adaptive control algorithm for realizing a vibratory angle measuring gyroscope so that rotation angle can be directly measured without integration of angular rate, thus eliminating the accumulation of numerical integration errors. The proposed control algorithm uses a trajectory following approach and the reference trajectory is generated by an ideal angle measuring gyroscope driven by the estimate of angular rate and the auxiliary sinusoidal input so that the persistent excitation condition is satisfied. The developed control algorithm can compensate for all types of fabrication imperfections such as coupled damping and stiffness, and mismatched stiffness and un-equal damping term in an on-line fashion. The simulation results show the feasibility and effectiveness of the developed control algorithm that is capable of directly measuring rotation angle without the integration of angular rate. PMID:22163667

  14. Climate Change and Some Other Implications of Vibratory Existence

    Directory of Open Access Journals (Sweden)

    Glenn McLaren

    2009-11-01

    Full Text Available Modern Process Philosophy began when Alfred North Whitehead realized that existence is primarily vibratory, not points but processes. Vibrations are best understood as sound waves, or through using auditory metaphors rather than visual ones. Our Universe is more like music than matter, but how does this help us better understand it? In this paper I use the example of the large ocean current oscillators that help drive our climate systems to reveal the more effective nature of auditory approaches. Through an auditory approach, we can better understand the ways these oscillations constrain and interact with other levels of oscillations as well as how they might be destroyed by other levels. This can then lead to us extending our ethics to the conservation of these oscillations.

  15. The Numerical FEM Model of the Kinematics of the Vibratory Shot Peening Process

    Directory of Open Access Journals (Sweden)

    Stanisław Bławucki

    2017-12-01

    Full Text Available The paper presents the results of numerical calculations, with the finite element method in the ABAQUS program environment, of the vibratory shot peening process with loose peening elements. The behaviour of shot peening elements was analysed in the kinematic aspect. The impact of the initial deployment of vibratory shot peening elements on their behaviour during processing was investigated, including the displacement, velocity, acceleration and the number of collisions. The way of determining the effectiveness of the processing with the vibratory shot peening was illustrated.

  16. Quinuclidinone derivative 6 induced apoptosis in human breast cancer cells via sphingomyelinase and JNK signaling.

    Science.gov (United States)

    Malki, Ahmed; El Ashry, El Sayed

    2012-10-01

    Novel quinuclidinone derivatives have been previously reported by our laboratory. In this study, we investigated the impact of two novel quinuclidinone derivatives 4 and 6 on apoptotic signaling in breast cancer cells (MCF-7) and their normal counterparts (MCF-12a). Our data revealed that derivatives 4 and 6 reduced proliferation and induced apoptosis in breast cancer cells. However, derivative 6 was less cytotoxic to normal breast epithelial cells than breast cancer cells; therefore, we focused on derivative 6 for further investigation. Flow cytometric analysis showed that quinuclidinone derivative 6 reduced the percentage of MCF-7 cells in G(2)/M which is confirmed by increased expression levels of cyclin B, while it arrests MCF12a in G1 phase judging from increased p21. Quinuclidinone derivative 6 increased expression levels of p53 and Bax at both protein and mRNA levels and reduced expression level of Mdm2, Bcl2, Akt and Bcl-XL It also increased mitochondrial apoptotic pathways by activating release of cytochrome c which is consistent with activation of caspase-9 as confirmed by caspase-9 inhibitor LEHD-CHO. Finally, it increased sphingomyelinase signaling and ceramide formation as well as its downstream targets ERK1/2, p38, and JNK. Inhibition of ERK1/2 with PD98059 exerted little effect on the derivative 6-induced apoptosis and p38 inhibition with SB203580 slightly lessened apoptosis, whereas inhibition of JNK with SP600125 markedly suppressed derivative 6-induced apoptosis. These results indicate that derivative-6 induced the activation of sphingomyelinase signaling and that JNK played a pivotal role in induction of apoptosis in human breast cancer cells. In vivo studies and molecular docking experiments are now in progress for further anticancer investigations.

  17. Electroejaculation versus vibratory stimulation in spinal cord injured men: sperm quality and patient preference.

    Science.gov (United States)

    Ohl, D A; Sønksen, J; Menge, A C; McCabe, M; Keller, L M

    1997-06-01

    We compared semen quality and patient preference between penile vibratory stimulation and electroejaculation in spinal cord injured men. We treated 11 spinal cord injured men with penile vibratory stimulation and electroejaculation in random order. End points examined were semen analysis, sperm functional assessment, and patient pain scores (1 to 10) and preferred procedure. Differences between the procedures were determined with the paired Student t test. There was no difference in antegrade sperm count but penile vibratory stimulation specimens had greater motility (26.0 versus 10.7%), viability (25.2 versus 9.7%) and motile sperm count (185.0 x 10(6) versus 97.0 x 10(6)). The retrograde sperm count was greater (but not significant) in electroejaculation patients. The total (antegrade plus retrograde) and motile sperm counts were not different. There was no difference in immunobead test (all negative), cervical mucus penetration or sperm penetration assay, although the percent hamster egg penetration approached significance (53.7% for penile vibratory stimulation versus 22.1% for electroejaculation, p = 0.06). There was no difference in the peak blood pressures and no complications were noted. Pain scores were significantly greater for electroejaculation compared to penile vibratory stimulation (5.2 versus 1.7, respectively). All patients preferred penile vibratory stimulation. There was a slight advantage in sperm quality and a high patient preference in favor of penile vibratory stimulation. Penile vibratory stimulation should be attempted first to induce ejaculation in spinal cord injured men, with electroejaculation reserved for failures.

  18. Sphincteric events during penile vibratory ejaculation and electroejaculation in men with spinal cord injuries.

    Science.gov (United States)

    Sønksen, J; Ohl, D A; Wedemeyer, G

    2001-02-01

    We investigate internal and external sphincter responses during penile vibratory stimulation and electroejaculation in men with spinal cord injury. Ejaculation induction with simultaneous recording of external and internal sphincter pressures was performed in 9 spinal cord injured men. Of the patients with upper motor neuron lesions 3 underwent penile vibratory stimulation and 3 underwent electroejaculation. In 3 men who did not respond to PVS, including 1 with upper motor neuron and 2 with lower motor neuron lesions, penile vibratory stimulation and subsequent electroejaculation were performed. In successful penile vibratory stimulation and electroejaculation upper motor neuron cases external sphincter pressure first reached a peak (average 180 cm. H2O) and subsequently decrease followed in 3 to 10 seconds by a peak in internal sphincter pressure (average 178 cm. H2O), which exceeded external sphincter pressure and ejaculation occurred. During electroejaculation, the pattern progressed, despite complete discontinuation of electrical stimulation. In electroejaculation, there was a trend for a more rapid return of external sphincter pressure greater than internal sphincter pressure, which may explain the electroejaculation retrograde fraction. In nonresponders external sphincter pressure never increased to more than 105 cm. H2O in response to penile vibratory stimulation and no ejaculation was induced. In nonresponders to penile vibratory stimulation, electroejaculation induced a typical sustained increase in internal sphincter pressure and external sphincter pressure but at lower peak pressures. Forceful contraction of the external sphincter followed by contraction of the internal sphincter always precedes ejaculation during electroejaculation and penile vibratory stimulation. Similarities between penile vibratory stimulation and electroejaculation suggest that the latter induces ejaculation via a complex neurological pathway rather than by simple direct end organ

  19. Inflammasome-Derived Exosomes Activate NF-κB Signaling in Macrophages.

    Science.gov (United States)

    Zhang, Yuehui; Liu, Fangbing; Yuan, Yanzhi; Jin, Chaozhi; Chang, Cheng; Zhu, Yunping; Zhang, Xiuyuan; Tian, Chunyan; He, Fuchu; Wang, Jian

    2017-01-06

    Exosomes are secreted small vesicles that mediate various biological processes, such as tumorigenesis and immune response. However, whether the inflammasome signaling leads to the change of constituent of exosomes and its roles in immune response remains to be determined. We isolated the exosomes from macrophages with treatment of mock, endotoxin, or endotoxin/nigericin. A label-free quantification method by MS/MS was used to identify the components of exosomes. In total, 2331 proteins were identified and 513 proteins were exclusively detected in exosomes with endotoxin and nigericin treatment. The differentially expressed proteins were classified by Gene Ontology and KEGG pathways. The immune response-related proteins and signaling pathways were specifically enriched in inflammasome-derived exosomes. Moreover, we treated macrophages with the exosomes from different stimulation. We found that inflammasome-derived exosomes directly activate NF-κB signaling pathway, while the control or endotoxin-derived exosomes have no effect. The inflammatory signaling was amplified in neighbor cells in an exosome-dependent way. The inflammasome-derived exosomes might be used to augment the immune response in disease treatment, and preventing the transfer of these exosomes might ameliorate autoimmune diseases.

  20. Jean-Martin Charcot and his vibratory chair for Parkinson disease.

    Science.gov (United States)

    Goetz, Christopher G

    2009-08-11

    Vibration therapy is currently used in diverse medical specialties ranging from orthopedics to urology to sports medicine. The celebrated 19th-century neurologist, J.-M. Charcot, used vibratory therapy to treat Parkinson disease (PD). This study analyzed printed writings by Charcot and other writers on vibratory therapy and accessed unpublished notes from the Salpêtrière Hospital, Paris. Charcot lectured on several occasions on vibratory therapy and its neurologic applications. He developed a vibration chair for patients with PD after he observed that patients were more comfortable and slept better after a train or carriage ride. He replicated this experience by having patients undergo daily 30-minute sessions in the automated vibratory chair (fauteuil trépidant). His junior colleague, Gilles de la Tourette, extended these observations and developed a helmet that vibrated the head on the premise that the brain responded directly to the pulsations. Although after Charcot's death vibratory therapy was not widely pursued, vibratory appliances are reemerging in 21st century medicine and can be retested using adaptations of Charcot's neurologic protocols.

  1. Vocal fold vibratory characteristics of healthy geriatric females--analysis of high-speed digital images.

    Science.gov (United States)

    Ahmad, Kartini; Yan, Yuling; Bless, Diane

    2012-11-01

    A high proportion of the geriatric population suffers from presbylaryngis and presbyphonia; however, our knowledge of vibratory patterns in this population is almost nonexistent. In this study, we investigate the vocal fold vibratory patterns of healthy elderly females to determine which features or combination of them could best describe the geriatric voices. Cross-sectional study with 20 elderly healthy females with no history of voice problems. Hilbert transformed glottal area waveforms (GAWs) from serial high-speed digital imaging of sustained phonation are used to provide quantitative measures of glottal vibratory characteristics and perturbations; open quotient, jitter, and shimmer. Nyquist plots provide interpretable patterns to portray the vibratory characteristics as clear, pressed, breathy, and atypical patterns. The GAW from most elderly speakers (50%) showed vibratory characteristics associated with a more pressed voice and higher glottal perturbation values: their Nyquist plot patterns show wide scatterings around the rim of the plot reflecting a much-reduced ability in sustaining vibratory oscillation; these were distinct differences from previously reported data on younger speakers. Qualitative examination revealed more anteriorly placed glottal gaps in the geriatric females. These findings have important implications in understanding voice production in the geriatric population and in helping to establish normal perturbation references among female speakers across age. Copyright © 2012 The Voice Foundation. All rights reserved.

  2. Semen quality of spinal cord injured men is better when obtained by vibratory stimulation versus electroejaculation.

    Science.gov (United States)

    Brackett, N L; Padron, O F; Lynne, C M

    1997-01-01

    Most spinal cord injured men require assisted ejaculation procedures to obtain semen, and the majority can achieve this result by vibratory stimulation or electroejaculation. We determined if semen obtained by vibratory stimulation differed in quality from that obtained by electroejaculation. Between subjects and within subjects designs were used. Of 77 spinal cord injured men 23 underwent vibratory stimulation only, 44 electroejaculation only and 10 both procedures. Antegrade, retrograde and total ejaculates were analyzed in each subject for total sperm count, percent motile sperm and percent sperm with rapid linear motion. With vibratory stimulation compared to electroejaculation the percent motile sperm and percent sperm with rapid linear motion were significantly greater, whereas total sperm count was similar, in the antegrade specimens and total ejaculates. This finding was true for different groups of subjects as well as within a group of the same subjects. Semen obtained by vibratory stimulation is of better quality than that obtained by electroejaculation. In medical practices that include assisted ejaculation of spinal cord injured men, we recommend obtaining a specimen by vibratory stimulation. If that method fails electroejaculation should be performed.

  3. A spatial-spectral approach for deriving high signal quality eigenvectors for remote sensing image transformations

    DEFF Research Database (Denmark)

    Rogge, Derek; Bachmann, Martin; Rivard, Benoit

    2014-01-01

    Spectral decorrelation (transformations) methods have long been used in remote sensing. Transformation of the image data onto eigenvectors that comprise physically meaningful spectral properties (signal) can be used to reduce the dimensionality of hyperspectral images as the number of spectrally......-line surveys, or temporal data sets as computational burden becomes significant. In this paper we present a spatial-spectral approach to deriving high signal quality eigenvectors for image transformations which possess an inherently ability to reduce the effects of noise. The approach applies a spatial...... and spectral subsampling to the data, which is accomplished by deriving a limited set of eigenvectors for spatially contiguous subsets. These subset eigenvectors are compiled together to form a new noise reduced data set, which is subsequently used to derive a set of global orthogonal eigenvectors. Data from...

  4. Variational Mode Extraction: a New Efficient Method to Derive Respiratory Signals from ECG.

    Science.gov (United States)

    Nazari, Mojtaba; Sakhaei, Sayed Mahmoud

    2017-07-31

    ECG-derived respiratory (EDR) signal is an effective and inexpensive method to monitor the respiration. Previous studies have shown that the empirical mode decomposition (EMD) techniques can satisfactorily extract the EDR signal, however their performances are degraded at the presence of noise. On the other hand, Variational Mode Decomposition (VMD) performs good robustness against noise. In applications such as EDR extraction, where a specific mode is in interest, VMD imposes unnecessary computational cost. In this paper, we consider the extraction of EDR as a problem of obtaining a specific mode of a signal and suggest a new method named as Variational Mode Extraction (VME). The method is established on the similar basis as VMD, with a new criterion: the residual signal after extracting the specific mode should have no or less energy at the center frequency of the mode. In this regard, VME is capable of solving the EDR problem by considering the EDR signal as a mode with approximate center frequency of zero. For verification, the respiratory rate signal is detected from EDR signal extracted by VME and compared it with those obtained by VMD, EMD-based methods and band-pass filtering. The results confirm that the new method can extract the EDR signal with a better accuracy, while performing much lower computational cost and higher convergence rate.

  5. fNIRS derived hemodynamic signals and electrodermal responses in a sequential risk-taking task.

    Science.gov (United States)

    Holper, Lisa; ten Brincke, Robert H W; Wolf, Martin; Murphy, Ryan O

    2014-04-04

    The study measured cortical hemodynamic signals and peripheral correlates of decision makers during a dynamic risky task, the Just One More task (JOM), in which the risky decision entails choosing whether to incrementally increase accumulated earnings at the risk of ruin (going bust ending up with nothing). Twenty subjects participated in multiple instantiations of this task in which the probability of ruin and size of the stakes varied. Physiological correlates were simultaneously quantified by functional near-infrared spectroscopy (fNIRS) over dorsolateral prefrontal cortex (DLPFC) and electrodermal activity (EDA). First, in the task decision phase (i.e., when subjects are contemplating options before making a choice) probability of ruin had a dissociating effect on fNIRS and EDA. fNIRS derived DLPFC hemodynamic signals reflected a subjective value signal, correlating positively with individual risk attitude. Contrary, EDA reflected the probability of ruin in terms of a common affective measure, irrespective of individuals׳ risk attitude. Second, during the task outcome phase (i.e., the time after subjects have made a choice and observed the outcomes) fNIRS and EDA revealed opposite patterns. While fNIRS derived DLPFC hemodynamic signals were larger in response to gains, EDA signals were larger in response to losses; both patterns were statistically independent of individual risk attitude. Lastly, fNIRS derived DLPFC hemodynamic signals in the decision phase correlated positively with the mean round earnings, providing a measure of the quality of the individual decision-making performance. Together with the positive correlation with individual risk attitude, our findings indicate that fNIRS signals, but not EDA, could be taken as a useful method for studying individual risk attitude and task performance in dynamic risky decision-making. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Sex differences in brain-derived neurotrophic factor signaling: Functions and implications.

    Science.gov (United States)

    Wei, Yi-Chao; Wang, Shao-Ran; Xu, Xiao-Hong

    2017-01-02

    Brain-derived neurotrophic factor (BDNF) regulates diverse processes such as neuronal survival, differentiation, and plasticity. Accumulating evidence suggests that molecular events that direct sexual differentiation of the brain interact with BDNF signaling pathways. This Mini-Review first examines potential hormonal and epigenetic mechanisms through which sex influences BDNF signaling. We then examine how sex-specific regulation of BDNF signaling supports the development and function of sexually dimorphic neural circuits that underlie male-specific genital reflexes in rats and song production in birds. Finally, we discuss the implications of sex differences in BDNF signaling for gender-biased presentation of neurological and psychiatric diseases such as Alzheimer's disease. Although this Mini-Review focuses on BDNF, we try to convey the general message that sex influences brain functions in complex ways and underscore the requirement for and challenge of expanding research on sex differences in neuroscience. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  7. Vibratory device for taking ocean floor sediment cores

    Energy Technology Data Exchange (ETDEWEB)

    Edigariav, Z.P.; Kudinov, E.I.; Sukhov, V.E.

    1973-04-04

    The present invention relates to devices for taking sediment cores from the ocean floor. It consists in a vibratory device, comprising a string of pipe, a vibrator disposed on the string of pipe for sinking the pipe into the ocean floor, an arrangement for providing for periodical engagement and disengagement of the vibrator with the string of pipe, a hoist providing for periodical displacement of the vibrator, which is originally disposed on the lower portion of the string of pipe, up the string as the latter is being sunk into the ocean floor, and operatively coupled with the engaging arrangement. A piston is freely displaceable in the string of pipe and fixed relative to the ocean floor when the pipe is being sunk, to retain the ocean floor sediments in the pipe. The core of sediment is pressed against the piston under the action of hydrostatic and atmospheric pressures. A system is provided for stabilizing the device consisting of a load platform, a float, and guide cables. (6 claims)

  8. Estimation of the second derivative of kinematic impact signals using fractional fourier domain filtering.

    Science.gov (United States)

    Georgakis, Apostolos; Subramaniam, Suba Raman

    2009-04-01

    A new filtering algorithm is proposed for the accurate estimation of the second derivatives of kinematic signals with impacts. The algorithm operates in predetermined consecutive fractional Fourier transform domains and amounts to an overall linear low-pass filter with time-varying cutoff threshold, which can successfully accommodate the impact-induced changes in the frequency content of the signals. The proposed method was applied to experimentally acquired displacement data and the results have demonstrated its promising performance that was found superior to both conventional techniques and recently introduced advanced schemes.

  9. Inhibition of platelet-derived growth factor signaling prevents muscle fiber growth during skeletal muscle hypertrophy.

    Science.gov (United States)

    Sugg, Kristoffer B; Korn, Michael A; Sarver, Dylan C; Markworth, James F; Mendias, Christopher L

    2017-03-01

    The platelet-derived growth factor receptors alpha and beta (PDGFRα and PDGFRβ) mark fibroadipogenic progenitor cells/fibroblasts and pericytes in skeletal muscle, respectively. While the role that these cells play in muscle growth and development has been evaluated, it was not known whether the PDGF receptors activate signaling pathways that control transcriptional and functional changes during skeletal muscle hypertrophy. To evaluate this, we inhibited PDGFR signaling in mice subjected to a synergist ablation muscle growth procedure, and performed analyses 3 and 10 days after induction of hypertrophy. The results from this study indicate that PDGF signaling is required for fiber hypertrophy, extracellular matrix production, and angiogenesis that occur during muscle growth. © 2017 Federation of European Biochemical Societies.

  10. Aerosol optical depth under "clear" sky conditions derived from sea surface reflection of lidar signals.

    Science.gov (United States)

    He, Min; Hu, Yongxiang; Huang, Jian Ping; Stamnes, Knut

    2016-12-26

    There are considerable demands for accurate atmospheric correction of satellite observations of the sea surface or subsurface signal. Surface and sub-surface reflection under "clear" atmospheric conditions can be used to study atmospheric correction for the simplest possible situation. Here "clear" sky means a cloud-free atmosphere with sufficiently small aerosol particles. The "clear" aerosol concept is defined according to the spectral dependence of the scattering cross section on particle size. A 5-year combined CALIPSO and AMSR-E data set was used to derive the aerosol optical depth (AOD) from the lidar signal reflected from the sea surface. Compared with the traditional lidar-retrieved AOD, which relies on lidar backscattering measurements and an assumed lidar ratio, the AOD retrieved through the surface reflectance method depends on both scattering and absorption because it is based on two-way attenuation of the lidar signal transmitted to and then reflected from the surface. The results show that the clear sky AOD derived from the surface signal agrees with the clear sky AOD available in the CALIPSO level 2 database in the westerly wind belt located in the southern hemisphere, but yields significantly higher aerosol loadings in the tropics and in the northern hemisphere.

  11. Activin/nodal signaling switches the terminal fate of human embryonic stem cell-derived trophoblasts.

    Science.gov (United States)

    Sarkar, Prasenjit; Randall, Shan M; Collier, Timothy S; Nero, Anthony; Russell, Teal A; Muddiman, David C; Rao, Balaji M

    2015-04-03

    Human embryonic stem cells (hESCs) have been routinely treated with bone morphogenetic protein and/or inhibitors of activin/nodal signaling to obtain cells that express trophoblast markers. Trophoblasts can terminally differentiate to either extravillous trophoblasts or syncytiotrophoblasts. The signaling pathways that govern the terminal fate of these trophoblasts are not understood. We show that activin/nodal signaling switches the terminal fate of these hESC-derived trophoblasts. Inhibition of activin/nodal signaling leads to formation of extravillous trophoblast, whereas loss of activin/nodal inhibition leads to the formation of syncytiotrophoblasts. Also, the ability of hESCs to form bona fide trophoblasts has been intensely debated. We have examined hESC-derived trophoblasts in the light of stringent criteria that were proposed recently, such as hypomethylation of the ELF5-2b promoter region and down-regulation of HLA class I antigens. We report that trophoblasts that possess these properties can indeed be obtained from hESCs. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Activin/Nodal Signaling Switches the Terminal Fate of Human Embryonic Stem Cell-derived Trophoblasts*

    Science.gov (United States)

    Sarkar, Prasenjit; Randall, Shan M.; Collier, Timothy S.; Nero, Anthony; Russell, Teal A.; Muddiman, David C.; Rao, Balaji M.

    2015-01-01

    Human embryonic stem cells (hESCs) have been routinely treated with bone morphogenetic protein and/or inhibitors of activin/nodal signaling to obtain cells that express trophoblast markers. Trophoblasts can terminally differentiate to either extravillous trophoblasts or syncytiotrophoblasts. The signaling pathways that govern the terminal fate of these trophoblasts are not understood. We show that activin/nodal signaling switches the terminal fate of these hESC-derived trophoblasts. Inhibition of activin/nodal signaling leads to formation of extravillous trophoblast, whereas loss of activin/nodal inhibition leads to the formation of syncytiotrophoblasts. Also, the ability of hESCs to form bona fide trophoblasts has been intensely debated. We have examined hESC-derived trophoblasts in the light of stringent criteria that were proposed recently, such as hypomethylation of the ELF5-2b promoter region and down-regulation of HLA class I antigens. We report that trophoblasts that possess these properties can indeed be obtained from hESCs. PMID:25670856

  13. Towards Investigating Global Warming Impact on Human Health Using Derivatives of Photoplethysmogram Signals

    Science.gov (United States)

    Elgendi, Mohamed; Norton, Ian; Brearley, Matt; Fletcher, Richard R.; Abbott, Derek; Lovell, Nigel H.; Schuurmans, Dale

    2015-01-01

    Recent clinical studies show that the contour of the photoplethysmogram (PPG) wave contains valuable information for characterizing cardiovascular activity. However, analyzing the PPG wave contour is difficult; therefore, researchers have applied first or higher order derivatives to emphasize and conveniently quantify subtle changes in the filtered PPG contour. Our hypothesis is that analyzing the whole PPG recording rather than each PPG wave contour or on a beat-by-beat basis can detect heat-stressed subjects and that, consequently, we will be able to investigate the impact of global warming on human health. Here, we explore the most suitable derivative order for heat stress assessment based on the energy and entropy of the whole PPG recording. The results of our study indicate that the use of the entropy of the seventh derivative of the filtered PPG signal shows promising results in detecting heat stress using 20-second recordings, with an overall accuracy of 71.6%. Moreover, the combination of the entropy of the seventh derivative of the filtered PPG signal with the root mean square of successive differences, or RMSSD (a traditional heart rate variability index of heat stress), improved the detection of heat stress to 88.9% accuracy. PMID:26473907

  14. Towards Investigating Global Warming Impact on Human Health Using Derivatives of Photoplethysmogram Signals.

    Science.gov (United States)

    Elgendi, Mohamed; Norton, Ian; Brearley, Matt; Fletcher, Richard R; Abbott, Derek; Lovell, Nigel H; Schuurmans, Dale

    2015-10-14

    Recent clinical studies show that the contour of the photoplethysmogram (PPG) wave contains valuable information for characterizing cardiovascular activity. However, analyzing the PPG wave contour is difficult; therefore, researchers have applied first or higher order derivatives to emphasize and conveniently quantify subtle changes in the filtered PPG contour. Our hypothesis is that analyzing the whole PPG recording rather than each PPG wave contour or on a beat-by-beat basis can detect heat-stressed subjects and that, consequently, we will be able to investigate the impact of global warming on human health. Here, we explore the most suitable derivative order for heat stress assessment based on the energy and entropy of the whole PPG recording. The results of our study indicate that the use Int. J. Environ. Res. Public Health 2015, 7 12777 of the entropy of the seventh derivative of the filtered PPG signal shows promising results in detecting heat stress using 20-second recordings, with an overall accuracy of 71.6%. Moreover, the combination of the entropy of the seventh derivative of the filtered PPG signal with the root mean square of successive differences, or RMSSD (a traditional heart rate variability index of heat stress), improved the detection of heat stress to 88.9% accuracy.

  15. Towards Investigating Global Warming Impact on Human Health Using Derivatives of Photoplethysmogram Signals

    Directory of Open Access Journals (Sweden)

    Mohamed Elgendi

    2015-10-01

    Full Text Available Recent clinical studies show that the contour of the photoplethysmogram (PPG wave contains valuable information for characterizing cardiovascular activity. However, analyzing the PPG wave contour is difficult; therefore, researchers have applied first or higher order derivatives to emphasize and conveniently quantify subtle changes in the filtered PPG contour. Our hypothesis is that analyzing the whole PPG recording rather than each PPG wave contour or on a beat-by-beat basis can detect heat-stressed subjects and that, consequently, we will be able to investigate the impact of global warming on human health. Here, we explore the most suitable derivative order for heat stress assessment based on the energy and entropy of the whole PPG recording. The results of our study indicate that the use of the entropy of the seventh derivative of the filtered PPG signal shows promising results in detecting heat stress using 20-second recordings, with an overall accuracy of 71.6%. Moreover, the combination of the entropy of the seventh derivative of the filtered PPG signal with the root mean square of successive differences, or RMSSD (a traditional heart rate variability index of heat stress, improved the detection of heat stress to 88.9% accuracy.

  16. A distributed code for colour in natural scenes derived from centre-surround filtered cone signals

    Directory of Open Access Journals (Sweden)

    Christian Johannes Kellner

    2013-09-01

    Full Text Available In the retina of trichromatic primates, chromatic information is encoded in an opponent fashion and transmitted to the lateral geniculate nucleus (LGN and visual cortex via parallel pathways. Chromatic selectivities of neurons in the LGN form two separate clusters, corresponding to two classes of cone opponency. In the visual cortex, however, the chromatic selectivities are more distributed, which is in accordance with a population code for colour. Previous studies of cone signals in natural scenes typically found opponent codes with chromatic selectivities corresponding to two directions in colour space. Here we investigated how the nonlinear spatiochromatic filtering in the retina influences the encoding of colour signals. Cone signals were derived from hyperspectral images of natural scenes and pre-processed by centre-surround filtering and rectification, resulting in parallel ON and OFF channels. Independent Component Analysis on these signals yielded a highly sparse code with basis functions that showed spatio-chromatic selectivities. In contrast to previous analyses of linear transformations of cone signals, chromatic selectivities were not restricted to two main chromatic axes, but were more continuously distributed in colour space, similar to the population code of colour in the early visual cortex. Our results indicate that spatiochromatic processing in the retina leads to a more distributed and more efficient code for natural scenes.

  17. A distributed code for color in natural scenes derived from center-surround filtered cone signals.

    Science.gov (United States)

    Kellner, Christian J; Wachtler, Thomas

    2013-01-01

    In the retina of trichromatic primates, chromatic information is encoded in an opponent fashion and transmitted to the lateral geniculate nucleus (LGN) and visual cortex via parallel pathways. Chromatic selectivities of neurons in the LGN form two separate clusters, corresponding to two classes of cone opponency. In the visual cortex, however, the chromatic selectivities are more distributed, which is in accordance with a population code for color. Previous studies of cone signals in natural scenes typically found opponent codes with chromatic selectivities corresponding to two directions in color space. Here we investigated how the non-linear spatio-chromatic filtering in the retina influences the encoding of color signals. Cone signals were derived from hyper-spectral images of natural scenes and preprocessed by center-surround filtering and rectification, resulting in parallel ON and OFF channels. Independent Component Analysis (ICA) on these signals yielded a highly sparse code with basis functions that showed spatio-chromatic selectivities. In contrast to previous analyses of linear transformations of cone signals, chromatic selectivities were not restricted to two main chromatic axes, but were more continuously distributed in color space, similar to the population code of color in the early visual cortex. Our results indicate that spatio-chromatic processing in the retina leads to a more distributed and more efficient code for natural scenes.

  18. Distinct effectors of platelet-derived growth factor receptor-α signaling are required for cell survival during embryogenesis

    OpenAIRE

    Van Stry, Melanie; Kazlauskas, Andrius; Schreiber, Stuart L.; Symes, Karen

    2005-01-01

    Platelet-derived growth factor receptor (PDGFR) signaling is essential for normal embryonic development in many organisms, including frog, mouse, zebrafish, and sea urchin. The mode of action of PDGFR signaling during early development is poorly understood, however, mostly because inhibition of signaling through either the PDGFRα or PDGFRβ is embryonic lethal. In Xenopus embryos, disruption of PDGFRα signaling causes migrating anterior mesoderm cells to lose direction and undergo apoptosis th...

  19. The effect of penile vibratory stimulation on male fertility potential, spasticity and neurogenic detrusor overactivity in spinal cord lesioned individuals

    DEFF Research Database (Denmark)

    Biering-Sørensen, F; Læssøe, Line; Sønksen, J

    2005-01-01

    Present the possibility for treatment of male infertility, spasticity, and neurogenic detrusor overactivity in spinal cord lesioned (SCL) individuals with penile vibratory stimulation (PVS).......Present the possibility for treatment of male infertility, spasticity, and neurogenic detrusor overactivity in spinal cord lesioned (SCL) individuals with penile vibratory stimulation (PVS)....

  20. Structural Calculations of Drip Shield Exposed to Vibratory Ground Motion

    Energy Technology Data Exchange (ETDEWEB)

    S. Mastilovic

    2003-06-16

    The objective of this calculation is twofold. First, to determine whether or not separation of interlocking drip shield (DS) segments occurs during vibratory ground motion. Second, if DS separation does not occur, to estimate the area of the DS for which the residual 1st principal stress exceeds a certain limit. (The area of DS plate-1 and DS plate-2 [see Attachment I] where the residual 1st principal stress exceeds a certain limit will be, for brevity, referred to as ''the damaged area'' throughout this document; also, DS plate-1 and DS plate-2 will be referred to, for brevity, as ''DS plates'' henceforth.) The stress limit used throughout this document is defined as 50 percent of yield strength of the DS plate material, Titanium Grade 7 (Ti-7) (SB-265 R52400), at temperature of 150 C. A set of 15 calculations is performed at two different annual frequencies of occurrence (annual exceedance frequency): 10{sup -6} per year (1/yr) and 10{sup -7} 1/yr . (Note: Due to computational problems only five realizations at 10{sup -7} 1/yr are presented in this document.) Additionally, one calculation is performed at the annual frequency of occurrence of 5 {center_dot} 10{sup -4} 1/yr. The scope of this document is limited to reporting whether or not the DS separation occurs. If the DS separation does not occur the scope is limited to reporting the calculation results in terms of the damaged area. All these results are evaluated for the DS plates. This calculation is intended for use in support of the Total System Performance Assessment-License Application seismicity modeling. This calculation is associated with the DS design and was performed by the Waste Package Design group. AP-3.12Q, ''Design Calculations and Analyses'' (Ref. 1) is used to perform the calculation and develop the document. The DS is classified as Quality Level 1 (Ref. 5, p. 7). Therefore, this calculation is subject to the Quality Assurance

  1. Data-Derived Modeling Characterizes Plasticity of MAPK Signaling in Melanoma

    Science.gov (United States)

    Bernardo-Faura, Marti; Massen, Stefan; Falk, Christine S.; Brady, Nathan R.; Eils, Roland

    2014-01-01

    The majority of melanomas have been shown to harbor somatic mutations in the RAS-RAF-MEK-MAPK and PI3K-AKT pathways, which play a major role in regulation of proliferation and survival. The prevalence of these mutations makes these kinase signal transduction pathways an attractive target for cancer therapy. However, tumors have generally shown adaptive resistance to treatment. This adaptation is achieved in melanoma through its ability to undergo neovascularization, migration and rearrangement of signaling pathways. To understand the dynamic, nonlinear behavior of signaling pathways in cancer, several computational modeling approaches have been suggested. Most of those models require that the pathway topology remains constant over the entire observation period. However, changes in topology might underlie adaptive behavior to drug treatment. To study signaling rearrangements, here we present a new approach based on Fuzzy Logic (FL) that predicts changes in network architecture over time. This adaptive modeling approach was used to investigate pathway dynamics in a newly acquired experimental dataset describing total and phosphorylated protein signaling over four days in A375 melanoma cell line exposed to different kinase inhibitors. First, a generalized strategy was established to implement a parameter-reduced FL model encoding non-linear activity of a signaling network in response to perturbation. Next, a literature-based topology was generated and parameters of the FL model were derived from the full experimental dataset. Subsequently, the temporal evolution of model performance was evaluated by leaving time-defined data points out of training. Emerging discrepancies between model predictions and experimental data at specific time points allowed the characterization of potential network rearrangement. We demonstrate that this adaptive FL modeling approach helps to enhance our mechanistic understanding of the molecular plasticity of melanoma. PMID:25188314

  2. Classification of subsurface objects using singular values derived from signal frames

    Science.gov (United States)

    Chambers, David H; Paglieroni, David W

    2014-05-06

    The classification system represents a detected object with a feature vector derived from the return signals acquired by an array of N transceivers operating in multistatic mode. The classification system generates the feature vector by transforming the real-valued return signals into complex-valued spectra, using, for example, a Fast Fourier Transform. The classification system then generates a feature vector of singular values for each user-designated spectral sub-band by applying a singular value decomposition (SVD) to the N.times.N square complex-valued matrix formed from sub-band samples associated with all possible transmitter-receiver pairs. The resulting feature vector of singular values may be transformed into a feature vector of singular value likelihoods and then subjected to a multi-category linear or neural network classifier for object classification.

  3. AMPA receptor-induced local brain-derived neurotrophic factor signaling mediates motor recovery after stroke.

    Science.gov (United States)

    Clarkson, Andrew N; Overman, Justine J; Zhong, Sheng; Mueller, Rudolf; Lynch, Gary; Carmichael, S Thomas

    2011-03-09

    Stroke is the leading cause of adult disability. Recovery after stroke shares similar molecular and cellular properties with learning and memory. A main component of learning-induced plasticity involves signaling through AMPA receptors (AMPARs). We systematically tested the role of AMPAR function in motor recovery in a mouse model of focal stroke. AMPAR function controls functional recovery beginning 5 d after the stroke. Positive allosteric modulators of AMPARs enhance recovery of limb control when administered after a delay from the stroke. Conversely, AMPAR antagonists impair motor recovery. The contributions of AMPARs to recovery are mediated by release of brain-derived neurotrophic factor (BDNF) in periinfarct cortex, as blocking local BDNF function in periinfarct cortex blocks AMPAR-mediated recovery and prevents the normal pattern of motor recovery. In contrast to a delayed AMPAR role in motor recovery, early administration of AMPAR agonists after stroke increases stroke damage. These findings indicate that the role of glutamate signaling through the AMPAR changes over time in stroke: early potentiation of AMPAR signaling worsens stroke damage, whereas later potentiation of the same signaling system improves functional recovery.

  4. Targeting Sonic Hedgehog Signaling by Compounds and Derivatives from Natural Products

    Directory of Open Access Journals (Sweden)

    Yu-Chuen Huang

    2013-01-01

    Full Text Available Cancer stem cells (CSCs are a major cause of cancer treatment failure, relapse, and drug resistance and are known to be responsible for cancer cell invasion and metastasis. The Sonic hedgehog (Shh signaling pathway is crucial to embryonic development. Intriguingly, the aberrant activation of the Shh pathway plays critical roles in developing CSCs and leads to angiogenesis, migration, invasion, and metastasis. Natural compounds and chemical structure modified derivatives from complementary and alternative medicine have received increasing attention as cancer chemopreventives, and their antitumor effects have been demonstrated both in vitro and in vivo. However, reports for their bioactivity against CSCs and specifically targeting Shh signaling remain limited. In this review, we summarize investigations of the compounds cyclopamine, curcumin, epigallocatechin-3-gallate, genistein, resveratrol, zerumbone, norcantharidin, and arsenic trioxide, with a focus on Shh signaling blockade. Given that Shh signaling antagonism has been clinically proven as effective strategy against CSCs, this review may be exploitable for development of novel anticancer agents from complementary and alternative medicine.

  5. Assessing Granger Causality in Electrophysiological Data: Removing the Adverse Effects of Common Signals via Bipolar Derivations.

    Science.gov (United States)

    Trongnetrpunya, Amy; Nandi, Bijurika; Kang, Daesung; Kocsis, Bernat; Schroeder, Charles E; Ding, Mingzhou

    2015-01-01

    Multielectrode voltage data are usually recorded against a common reference. Such data are frequently used without further treatment to assess patterns of functional connectivity between neuronal populations and between brain areas. It is important to note from the outset that such an approach is valid only when the reference electrode is nearly electrically silent. In practice, however, the reference electrode is generally not electrically silent, thereby adding a common signal to the recorded data. Volume conduction further complicates the problem. In this study we demonstrate the adverse effects of common signals on the estimation of Granger causality, which is a statistical measure used to infer synaptic transmission and information flow in neural circuits from multielectrode data. We further test the hypothesis that the problem can be overcome by utilizing bipolar derivations where the difference between two nearby electrodes is taken and treated as a representation of local neural activity. Simulated data generated by a neuronal network model where the connectivity pattern is known were considered first. This was followed by analyzing data from three experimental preparations where a priori predictions regarding the patterns of causal interactions can be made: (1) laminar recordings from the hippocampus of an anesthetized rat during theta rhythm, (2) laminar recordings from V4 of an awake-behaving macaque monkey during alpha rhythm, and (3) ECoG recordings from electrode arrays implanted in the middle temporal lobe and prefrontal cortex of an epilepsy patient during fixation. For both simulation and experimental analysis the results show that bipolar derivations yield the expected connectivity patterns whereas the untreated data (referred to as unipolar signals) do not. In addition, current source density signals, where applicable, yield results that are close to the expected connectivity patterns, whereas the commonly practiced average re-reference method

  6. Heparan sulfate dependent signaling of fibroblast growth factor (FGF) 18 by chondrocyte-derived perlecan

    Science.gov (United States)

    Chuang, Christine Y.; Lord, Megan S.; Melrose, James; Rees, Martin D.; Knox, Sarah M.; Freeman, Craig; Iozzo, Renato V.; Whitelock, John M.

    2010-01-01

    Perlecan is a large multi-domain proteoglycan which is essential for normal cartilage development. In this study perlecan was localized in the pericellular matrix of hypertrophic chondrocytes in developing human cartilage rudiments. Perlecan immunopurified from medium conditioned by cultured human fetal chondrocytes was found to be substituted with heparan sulfate (HS), chondroitin sulfate (CS) and keratan sulfate (KS). Ligand and carbohydrate engagement (LACE) assays demonstrated that immunopurified chondrocyte-derived perlecan formed HS dependent ternary complexes with fibroblast growth factors (FGF) 2 and either FGFR receptors (FGFRs) 1 or 3, however these complexes were not biologically active in the BaF32 cell system. Chondrocyte-derived perlecan also formed HS dependent ternary complexes with FGF18 and FGFR3. The proliferation of BaF32 cells expressing FGFR3 was promoted by chondrocyte-derived perlecan in the presence of FGF18 and this activity was reduced by digesting the HS with either heparinase III or mammalian heparanase. These data suggest that FGF2 and 18 bind to discrete structures on the HS chains attached to chondrocyte-derived perlecan which modulate the growth factor activities. The presence and activity of mammalian heparanase may be important in the turnover of HS and subsequent signaling required for the establishment and maintenance of functional osteo-chondral junctions in long bone growth. PMID:20507176

  7. Theoretical and experimental study of the transport of granular materials by inclined vibratory conveyors

    NARCIS (Netherlands)

    Sloot, E.M.; Sloot, E.M.; Kruyt, Nicolaas P.

    1996-01-01

    A theoretical and experimental study was made of the conveying speed with which granular materials are transported by vibratory conveyors. The basic assumption made is that the layer of granular material can be considered as a point mass. The theory incorporates rest, slide, and flight phases of the

  8. Considerations Concerning the Dynamics of Vibratory Mills Used in Powders’ Mechanical Milling Process

    Directory of Open Access Journals (Sweden)

    Radu Panaitescu-Liess

    2010-01-01

    Full Text Available Dynamic mechanical milling process in a powder mill was studied by analyzing the vibratory effects of vibration and shock phenomena on the material microstructure ground. During the milling process, there were noticed both distinct modes of ball motion: the one generated by the periodic vibration and the one produced by chaotic vibration.

  9. Comparison of Axial Capacity of Vibratory-Driven Piles to Impact-Driven Piles.

    Science.gov (United States)

    1987-09-01

    vibratory-driven process results in less compacatiori at the pile tip, thus lowering the tip capacity. Hunter and Davisson (1969), in their...Loading Tests," US Army Engineer District, Little Rock, Ark. Hunter, A. A., and Davisson , M. T. (1969). "Measurement of Pile Load Transfer," Performance

  10. Effects of vibratory pile driver noise on echolocation and vigilance in bottlenose dolphins (Tursiops truncatus).

    Science.gov (United States)

    Branstetter, Brian K; Bowman, Victoria F; Houser, Dorian S; Tormey, Megan; Banks, Patchouly; Finneran, James J; Jenkins, Keith

    2018-01-01

    Vibratory pile drivers, used for marine construction, can produce sustained, high sound pressure levels (SPLs) in areas that overlap with dolphin habitats. Dolphins rely on echolocation for navigation, detecting predators and prey, and to coordinate group behavior. This study examined the effects of vibratory pile driver noise on dolphin sustained target detection capabilities through echolocation. Five dolphins were required to scan their enclosure and indicate the occurrences of phantom echoes during five different source levels of vibratory pile driver playback sound (no-playback control, 110, 120, 130, and 140 dB re 1 μPa). Three of the dolphins demonstrated a significant decrease in target detection performance at 140 dB playback level that was associated with an almost complete secession of echolocation activity. The performance of two dolphins was not affected. All dolphins rapidly returned to baseline levels of target detection performance by their second replication. However, an increased number of clicks was produced at the highest playback SPL. The data suggest that the decrease in vigilant behavior was due to the vibratory pile driver noise distracting the dolphins and decreasing their motivation to perform the task.

  11. ANALYSIS OF VIBRATORY PROTECTION SYSTEM VIBRATION DURING HARMONIC AND POLYHARMONIC EXCITATIONS

    Directory of Open Access Journals (Sweden)

    T. N. Mikulik

    2011-01-01

    Full Text Available The paper considers a mathematical model of local «driver-seat» system and an algorithm for vibratory loading formation at external actions. Results of the investigations on the system vibration according to minimum vibration acceleration depending on transfer force factor acting on the seat and a vibration isolation factor are presented in the paper.

  12. Wave radiation from vibratory and impact pile driving in a layered acousto-elastic medium

    NARCIS (Netherlands)

    Tsouvalas, A.; Metrikine, A.

    2014-01-01

    A steel monopile is the most common foundation type of a wind turbine installed offshore and is driven into place with the help of vibratory or impact hammers. Underwater noise generated during the installation of steel monopiles has recently received considerable attention from international

  13. Assessment of Penile Vibratory Stimulation as a Management Strategy in Men with Secondary Retarded Orgasm

    Science.gov (United States)

    Nelson, Christian J.; Ahmed, Absaar; Valenzuela, Rolando; Parker, Marilyn; Mulhall, John P.

    2016-01-01

    OBJECTIVES To evaluate the effectiveness of penile vibratory stimulation for the management of retarded orgasm. Retarded orgasm, a condition characterized by difficulty achieving orgasm and ejaculation, is one of the most recalcitrant of the male sexual dysfunctions. Currently, no evidence-based treatments have been proven to ameliorate this condition. METHODS Men who had a complete inability to achieve an orgasm during sexual relations in the previous 3 months were instructed in the use of penile vibratory stimulation. The men’s responses were measured by self-report of orgasm function and using the orgasm and satisfaction domains of the International Index of Erectile Function. The responses were assessed at baseline (admission into the study) and at 3 and 6 months. RESULTS A total of 36 men met the inclusion criteria, and 72% reported the restoration of orgasm. These responders reported that orgasm during sexual relations occurred 62% of the time. A statistically and clinically significant increase occurred in the orgasm and satisfaction domains of the International Index of Erectile Function between the baseline visit and the 3-month follow-up visit. These gains were sustained at 6 months. CONCLUSIONS Penile vibratory stimulation is an effective treatment for retarded orgasm. Penile vibratory stimulation should be integrated into current cognitive-behavioral sex therapy techniques to achieve maximal effectiveness and satisfaction. PMID:17382163

  14. PACAP38/PAC1 signaling induces bone marrow-derived cells homing to ischemic brain.

    Science.gov (United States)

    Lin, Chen-Huan; Chiu, Lian; Lee, Hsu-Tung; Chiang, Chun-Wei; Liu, Shih-Ping; Hsu, Yung-Hsiang; Lin, Shinn-Zong; Hsu, Chung Y; Hsieh, Chia-Hung; Shyu, Woei-Cherng

    2015-04-01

    Understanding stem cell homing, which is governed by environmental signals from the surrounding niche, is important for developing effective stem cell-based repair strategies. The molecular mechanism by which the brain under ischemic stress recruits bone marrow-derived cells (BMDCs) to the vascular niche remains poorly characterized. Here we report that hypoxia-inducible factor-1α (HIF-1α) activation upregulates pituitary adenylate cyclase-activating peptide 38 (PACAP38), which in turn activates PACAP type 1 receptor (PAC1) under hypoxia in vitro and cerebral ischemia in vivo. BMDCs homing to endothelial cells in the ischemic brain are mediated by HIF-1α activation of the PACAP38-PAC1 signaling cascade followed by upregulation of cellular prion protein and α6-integrin to enhance the ability of BMDCs to bind laminin in the vascular niche. Exogenous PACAP38 confers a similar effect in facilitating BMDCs homing into the ischemic brain, resulting in reduction of ischemic brain injury. These findings suggest a novel HIF-1α-activated PACAP38-PAC1 signaling process in initiating BMDCs homing into the ischemic brain for reducing brain injury and enhancing functional recovery after ischemic stroke. © 2015 The Authors. STEM CELLS Published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  15. Characterization of HGF/Met Signaling in Cell Lines Derived From Urothelial Carcinoma of the Bladder

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Young H. [Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Apolo, Andrea B. [Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Agarwal, Piyush K.; Bottaro, Donald P., E-mail: dbottaro@helix.nih.gov [Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2014-11-25

    There is mounting evidence of oncogenic hepatocyte growth factor (HGF)/Met signaling in urothelial carcinoma (UC) of the bladder. The effects of three kinase inhibitors, cabozantinib, crizotinib and EMD1214063, on HGF-driven signaling and cell growth, invasion and tumorigenicity were analyzed in cultured UC cell lines. SW780 xenograft growth in SCID and human HGF knock-in SCID (hHGF/SCID) mice treated with cabozantinib or vehicle, as well as tumor levels of Met and pMet, were also determined. Met content was robust in most UC-derived cell lines. Basal pMet content and effector activation state in quiescent cells were low, but significantly enhanced by added HGF, as were cell invasion, proliferation and anchorage independent growth. These HGF-driven effects were reversed by Met inhibitor treatment. Tumor xenograft growth was significantly higher in hHGF/SCID mice vs. SCID mice and significantly inhibited by cabozantinib, as was tumor phospho-Met content. These studies indicate the prevalence and functionality of the HGF/Met signaling pathway in UC cells, suggest that paracrine HGF may contribute to UC tumor growth and progression, and that support further preclinical investigation of Met inhibitors for the treatment of UC is warranted.

  16. Control of Vibratory Energy Harvesters in the Presence of Nonlinearities and Power-Flow Constraints

    Science.gov (United States)

    Cassidy, Ian L.

    Over the past decade, a significant amount of research activity has been devoted to developing electromechanical systems that can convert ambient mechanical vibrations into usable electric power. Such systems, referred to as vibratory energy harvesters, have a number of useful of applications, ranging in scale from self-powered wireless sensors for structural health monitoring in bridges and buildings to energy harvesting from ocean waves. One of the most challenging aspects of this technology concerns the efficient extraction and transmission of power from transducer to storage. Maximizing the rate of power extraction from vibratory energy harvesters is further complicated by the stochastic nature of the disturbance. The primary purpose of this dissertation is to develop feedback control algorithms which optimize the average power generated from stochastically-excited vibratory energy harvesters. This dissertation will illustrate the performance of various controllers using two vibratory energy harvesting systems: an electromagnetic transducer embedded within a flexible structure, and a piezoelectric bimorph cantilever beam. Compared with piezoelectric systems, large-scale electromagnetic systems have received much less attention in the literature despite their ability to generate power at the watt--kilowatt scale. Motivated by this observation, the first part of this dissertation focuses on developing an experimentally validated predictive model of an actively controlled electromagnetic transducer. Following this experimental analysis, linear-quadratic-Gaussian control theory is used to compute unconstrained state feedback controllers for two ideal vibratory energy harvesting systems. This theory is then augmented to account for competing objectives, nonlinearities in the harvester dynamics, and non-quadratic transmission loss models in the electronics. In many vibratory energy harvesting applications, employing a bi-directional power electronic drive to actively

  17. EEG derivations providing auditory steady-state responses with high signal-to-noise ratios in infants.

    NARCIS (Netherlands)

    Reijden, C.S. van der; Mens, L.H.M.; Snik, A.F.M.

    2005-01-01

    OBJECTIVE: To identify EEG derivations that yield high signal-to-noise ratios (SNRs) of the auditory steady-state response (ASSR) in infants aged 0 to 5 months. DESIGN: The ASSR was recorded simultaneously from 10 EEG derivations in a monopolar montage in 20 sleeping infants. Stimuli were tones of

  18. Reconstruction of the first-derivative EPR spectrum from multiple harmonics of the field-modulated continuous wave signal.

    Science.gov (United States)

    Tseitlin, Mark; Eaton, Sandra S; Eaton, Gareth R

    2011-04-01

    Selection of the amplitude of magnetic field modulation for continuous wave electron paramagnetic resonance (EPR) often is a trade-off between sensitivity and resolution. Increasing the modulation amplitude improves the signal-to-noise ratio, S/N, at the expense of broadening the signal. Combining information from multiple harmonics of the field-modulated signal is proposed as a method to obtain the first derivative spectrum with minimal broadening and improved signal-to-noise. The harmonics are obtained by digital phase-sensitive detection of the signal at the modulation frequency and its integer multiples. Reconstruction of the first-derivative EPR line is done in the Fourier conjugate domain where each harmonic can be represented as the product of the Fourier transform of the 1st derivative signal with an analytical function. The analytical function for each harmonic can be viewed as a filter. The Fourier transform of the 1st derivative spectrum can be calculated from all available harmonics by solving an optimization problem with the goal of maximizing the S/N. Inverse Fourier transformation of the result produces the 1st derivative EPR line in the magnetic field domain. The use of modulation amplitude greater than linewidth improves the S/N, but does not broaden the reconstructed spectrum. The method works for an arbitrary EPR line shape, but is limited to the case when magnetization instantaneously follows the modulation field, which is known as the adiabatic approximation. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. The signalling imprints of nanoparticle uptake by bone marrow derived dendritic cells.

    Science.gov (United States)

    Karlson, Tanya De L; Kong, Ying Ying; Hardy, Charles L; Xiang, Sue Dong; Plebanski, Magdalena

    2013-05-01

    Nanoparticles (NP) possess remarkable adjuvant and carrier capacity, therefore are used in the development of various vaccine formulations. Our previous studies demonstrated that inert non-toxic 40-50 nm polystyrene NP (PS-NP) can promote strong CD8 T cell and antibody responses to the antigen, in the absence of observable inflammatory responses. Furthermore, instillation of PS-NP inhibited the development of allergic airway inflammation by induction of an immunological imprint via modulation of dendritic cell (DC) function without inducing oxidative stress in the lungs in mice. This is in contrast to many studies which show that a variety of ambient and man-made NP promote lung immunopathology, raising concerns generally about the safe use of NPs in biomedicine. Most NPs are capable of inducing inflammatory pathways in DC largely mediated by signalling via the extracellular signal-regulated kinase 1/2 (ERK). Herein, we investigate whether PS-NPs also activate ERK in DC in vitro. Our data show that PS-NP do not induce ERK activation in two different types of bone marrow derived (BM) DC cultures (expanded with GM-CSF or with GM-CSF together with IL-4). The absence of such signalling was not due to lack of PS-NP uptake by BM-DC as confirmed by confocal microscopy and flow cytometry. The process of NP uptake by DC usually initiates ERK signalling, suggesting an unusual uptake pathway may be engaged by PS-NPs. Indeed, data herein showns that uptake of PS-NP by BM-DC was substantially inhibited by phorbol myristate acetate (PMA) but not cytochalasin D (CCD), suggesting an uptake pathway utilising caveole for PS-NP. Together these data show that BM-DC take up PS-NP via a caveole-dependent pathway which does not trigger ERK signalling which may explain their efficient uptake by DC, without the concomitant activation of conventional inflammatory pathways. Copyright © 2013. Published by Elsevier Inc.

  20. Clenbuterol induces cardiac myocyte hypertrophy via paracrine signalling and fibroblast-derived IGF-1.

    Science.gov (United States)

    Bhavsar, Pankaj K; Brand, Nigel J; Felkin, Leanne E; Luther, Pradeep K; Cullen, Martin E; Yacoub, Magdi H; Barton, Paul J R

    2010-12-01

    The β(2)-selective adrenoreceptor agonist clenbuterol promotes both skeletal and cardiac muscle hypertrophy and is undergoing clinical trials in the treatment of muscle wasting and heart failure. We have previously demonstrated that clenbuterol induces a mild physiological ventricular hypertrophy in vivo with normal contractile function and without induction of α-skeletal muscle actin (αSkA), a marker of pathological hypertrophy. The mechanisms of this response remain poorly defined. In this study, we examine the direct action of clenbuterol on cardiocyte cultures in vitro. Clenbuterol treatment resulted in increased cell size of cardiac myocytes with increased protein accumulation and myofibrillar organisation characteristic of hypertrophic growth. Real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) revealed elevated mRNA expression of ANP and brain natriuretic peptide (BNP) but without change in αSkA, consistent with physiological hypertrophic growth. Clenbuterol-treated cultures also showed elevated insulin-like growth factor I (IGF-1) mRNA and activation of the protein kinase Akt. Addition of either IGF-1 receptor-blocking antibodies or LY294002 in order to inhibit phosphatidylinositol 3-kinase, a downstream effector of the IGF-1 receptor, inhibited the hypertrophic response indicating that IGF-1 signalling is required. IGF-1 expression localised primarily to the minor population of cardiac fibroblasts present in the cardiocyte cultures. Together these data show that clenbuterol acts to induce mild cardiac hypertrophy in cardiac myocytes via paracrine signalling involving fibroblast-derived IGF-1.

  1. Large-scale models of signal propagation in human cells derived from discovery phosphoproteomic data.

    Science.gov (United States)

    Terfve, Camille D A; Wilkes, Edmund H; Casado, Pedro; Cutillas, Pedro R; Saez-Rodriguez, Julio

    2015-09-10

    Mass spectrometry is widely used to probe the proteome and its modifications in an untargeted manner, with unrivalled coverage. Applied to phosphoproteomics, it has tremendous potential to interrogate phospho-signalling and its therapeutic implications. However, this task is complicated by issues of undersampling of the phosphoproteome and challenges stemming from its high-content but low-sample-throughput nature. Hence, methods using such data to reconstruct signalling networks have been limited to restricted data sets and insights (for example, groups of kinases likely to be active in a sample). We propose a new method to handle high-content discovery phosphoproteomics data on perturbation by putting it in the context of kinase/phosphatase-substrate knowledge, from which we derive and train logic models. We show, on a data set obtained through perturbations of cancer cells with small-molecule inhibitors, that this method can study the targets and effects of kinase inhibitors, and reconcile insights obtained from multiple data sets, a common issue with these data.

  2. Sex differences in brain-derived neurotrophic factor signaling and functions.

    Science.gov (United States)

    Chan, Chi Bun; Ye, Keqiang

    2017-01-02

    Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family that plays a critical role in numerous neuronal activities. Recent studies have indicated that some functions or action mechanisms of BDNF vary in a sex-dependent manner. In particular, BDNF content in some brain parts and the tendency to develop BDNF deficiency-related diseases such as depression are greater in female animals. With the support of relevant studies, it has been suggested that sex hormones or steroids can modulate the activities of BDNF, which may account for its functional discrepancy in different sexes. Indeed, the cross-talk between BDNF and sex steroids has been detected for decades, and some sex steroids, such as estrogen, have a positive regulatory effect on BDNF expression and signaling. Thus, the sex of animal models that are used in studying the functions of BDNF is critical. This Mini-Review summarizes our current findings on the differences in expression, signaling, and functions of BDNF between sexes. We also discuss the potential mechanisms for mediating these differential responses, with a specific emphasis on sex steroids. By presenting and discussing these findings, we seek to encourage researchers to take sex influences into consideration when designing experiments, interpreting results, and drawing conclusions. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. Macrophage-derived IL-10 mediates mucosal repair by epithelial WISP-1 signaling.

    Science.gov (United States)

    Quiros, Miguel; Nishio, Hikaru; Neumann, Philipp A; Siuda, Dorothee; Brazil, Jennifer C; Azcutia, Veronica; Hilgarth, Roland; O'Leary, Monique N; Garcia-Hernandez, Vicky; Leoni, Giovanna; Feng, Mingli; Bernal, Gabriela; Williams, Holly; Dedhia, Priya H; Gerner-Smidt, Christian; Spence, Jason; Parkos, Charles A; Denning, Timothy L; Nusrat, Asma

    2017-09-01

    In response to injury, epithelial cells migrate and proliferate to cover denuded mucosal surfaces and repair the barrier defect. This process is orchestrated by dynamic crosstalk between immune cells and the epithelium; however, the mechanisms involved remain incompletely understood. Here, we report that IL-10 was rapidly induced following intestinal mucosal injury and was required for optimal intestinal mucosal wound closure. Conditional deletion of IL-10 specifically in CD11c-expressing cells in vivo implicated macrophages as a critical innate immune contributor to IL-10-induced wound closure. Consistent with these findings, wound closure in T cell- and B cell-deficient Rag1-/- mice was unimpaired, demonstrating that adaptive immune cells are not absolutely required for this process. Further, following mucosal injury, macrophage-derived IL-10 resulted in epithelial cAMP response element-binding protein (CREB) activation and subsequent synthesis and secretion of the pro-repair WNT1-inducible signaling protein 1 (WISP-1). WISP-1 induced epithelial cell proliferation and wound closure by activating epithelial pro-proliferative pathways. These findings define the involvement of macrophages in regulating an IL-10/CREB/WISP-1 signaling axis, with broad implications in linking innate immune activation to mucosal wound repair.

  4. Intestinal Epithelial-Derived TAK1 Signaling Is Essential for Cytoprotection against Chemical-Induced Colitis

    Science.gov (United States)

    Kim, Jae-Young; Kajino-Sakamoto, Rie; Omori, Emily; Jobin, Christian; Ninomiya-Tsuji, Jun

    2009-01-01

    Background We have previously reported that intestinal epithelium-specific TAK1 deleted mice exhibit severe inflammation and mortality at postnatal day 1 due to TNF-induced epithelial cell death. Although deletion of TNF receptor 1 (TNFR1) can largely rescue those neonatal phenotypes, mice harboring double deletion of TNF receptor 1 (TNFR1) and intestinal epithelium-specific deletion of TAK1 (TNFR1KO/TAK1IEKO) still occasionally show increased inflammation. This indicates that TAK1 is important for TNF-independent regulation of intestinal integrity. Methodology/Principal Findings In this study, we investigated the TNF-independent role of TAK1 in the intestinal epithelium. Because the inflammatory conditions were sporadically developed in the double mutant TNFR1KO/TAK1IEKO mice, we hypothesize that epithelial TAK1 signaling is important for preventing stress-induced barrier dysfunction. To test this hypothesis, the TNFR1KO/TAK1IEKO mice were subjected to acute colitis by administration of dextran sulfate sodium (DSS). We found that loss of TAK1 significantly augments DSS-induced experimental colitis. DSS induced weight loss, intestinal damages and inflammatory markers in TNFR1KO/TAK1IEKO mice at higher levels compared to the TNFR1KO control mice. Apoptosis was strongly induced and epithelial cell proliferation was decreased in the TAK1-deficient intestinal epithelium upon DSS exposure. These suggest that epithelial-derived TAK1 signaling is important for cytoprotection and repair against injury. Finally, we showed that TAK1 is essential for interleukin 1- and bacterial components-induced expression of cytoprotective factors such as interleukin 6 and cycloxygenase 2. Conclusions Homeostatic cytokines and microbes-induced intestinal epithelial TAK1 signaling regulates cytoprotective factors and cell proliferation, which is pivotal for protecting the intestinal epithelium against injury. PMID:19234607

  5. Intestinal epithelial-derived TAK1 signaling is essential for cytoprotection against chemical-induced colitis.

    Directory of Open Access Journals (Sweden)

    Jae-Young Kim

    Full Text Available We have previously reported that intestinal epithelium-specific TAK1 deleted mice exhibit severe inflammation and mortality at postnatal day 1 due to TNF-induced epithelial cell death. Although deletion of TNF receptor 1 (TNFR1 can largely rescue those neonatal phenotypes, mice harboring double deletion of TNF receptor 1 (TNFR1 and intestinal epithelium-specific deletion of TAK1 (TNFR1KO/TAK1(IEKO still occasionally show increased inflammation. This indicates that TAK1 is important for TNF-independent regulation of intestinal integrity.In this study, we investigated the TNF-independent role of TAK1 in the intestinal epithelium. Because the inflammatory conditions were sporadically developed in the double mutant TNFR1KO/TAK1(IEKO mice, we hypothesize that epithelial TAK1 signaling is important for preventing stress-induced barrier dysfunction. To test this hypothesis, the TNFR1KO/TAK1(IEKO mice were subjected to acute colitis by administration of dextran sulfate sodium (DSS. We found that loss of TAK1 significantly augments DSS-induced experimental colitis. DSS induced weight loss, intestinal damages and inflammatory markers in TNFR1KO/TAK1(IEKO mice at higher levels compared to the TNFR1KO control mice. Apoptosis was strongly induced and epithelial cell proliferation was decreased in the TAK1-deficient intestinal epithelium upon DSS exposure. These suggest that epithelial-derived TAK1 signaling is important for cytoprotection and repair against injury. Finally, we showed that TAK1 is essential for interleukin 1- and bacterial components-induced expression of cytoprotective factors such as interleukin 6 and cycloxygenase 2.Homeostatic cytokines and microbes-induced intestinal epithelial TAK1 signaling regulates cytoprotective factors and cell proliferation, which is pivotal for protecting the intestinal epithelium against injury.

  6. Endogenous signaling by omega-3 docosahexaenoic acid-derived mediators sustains homeostatic synaptic and circuitry integrity.

    Science.gov (United States)

    Bazan, Nicolas G; Musto, Alberto E; Knott, Eric J

    2011-10-01

    The harmony and function of the complex brain circuits and synapses are sustained mainly by excitatory and inhibitory neurotransmission, neurotrophins, gene regulation, and factors, many of which are incompletely understood. A common feature of brain circuit components, such as dendrites, synaptic membranes, and other membranes of the nervous system, is that they are richly endowed in docosahexaenoic acid (DHA), the main member of the omega-3 essential fatty acid family. DHA is avidly retained and concentrated in the nervous system and known to play a role in neuroprotection, memory, and vision. Only recently has it become apparent why the surprisingly rapid increases in free (unesterified) DHA pool size take place at the onset of seizures or brain injury. This phenomenon began to be clarified by the discovery of neuroprotectin D1 (NPD1), the first-uncovered bioactive docosanoid formed from free DHA through 15-lipoxygenase-1 (15-LOX-1). NPD1 synthesis includes, as agonists, oxidative stress and neurotrophins. The evolving concept is that DHA-derived docosanoids set in motion endogenous signaling to sustain homeostatic synaptic and circuit integrity. NPD1 is anti-inflammatory, displays inflammatory resolving activities, and induces cell survival, which is in contrast to the pro-inflammatory actions of the many of omega-6 fatty acid family members. We highlight here studies relevant to the ability of DHA to sustain neuronal function and protect synapses and circuits in the context of DHA signalolipidomics. DHA signalolipidomics comprises the integration of the cellular/tissue mechanism of DHA uptake, its distribution among cellular compartments, the organization and function of membrane domains containing DHA phospholipids, and the precise cellular and molecular events revealed by the uncovering of signaling pathways regulated by docosanoids endowed with prohomeostatic and cell survival bioactivity. Therefore, this approach offers emerging targets for prevention

  7. Predicting vibratory stresses from aero-acoustic loads

    Science.gov (United States)

    Shaw, Matthew D.

    Sonic fatigue has been a concern of jet aircraft engineers for many years. As engines become more powerful, structures become more lightly damped and complex, and materials become lighter, stiffer, and more complicated, the need to understand and predict structural response to aeroacoustic loads becomes more important. Despite decades of research, vibration in panels caused by random pressure loads, such as those found in a supersonic jet, is still difficult to predict. The work in this research improves on current prediction methods in several ways, in particular for the structural response due to wall pressures induced by supersonic turbulent flows. First, solutions are calculated using time-domain input pressure loads that include shock cells and their interaction with turbulent flow. The solutions include both mean (static) and oscillatory components. Second, the time series of stresses are required for many fatigue assessment counting algorithms. To do this, a method is developed to compute time-dependent solutions in the frequency domain. The method is first applied to a single-degree-of-freedom system. The equations of motion are derived and solved in both the frequency domain and the time domain. The pressure input is a random (broadband) signal representative of jet flow. The method is then applied to a simply-supported beam vibrating in flexure using a line of pressure inputs computed with computational fluid dynamics (CFD). A modal summation approach is used to compute structural response. The coupling between the pressure field and the structure, through the joint acceptance, is reviewed and discussed for its application to more complicated structures. Results from the new method and from a direct time domain method are compared for method verification. Because the match is good and the new frequency domain method is faster computationally, it is chosen for use in a more complicated structure. The vibration of a two-dimensional panel loaded by jet

  8. Obtention of hydroxyapatite submicrometric of bovine origin by vibratory grinding for rapid prototyping; Obtencao de hidroxiapatita submicrometrica de origem bovina por moagem vibratoria visando prototipagem rapida

    Energy Technology Data Exchange (ETDEWEB)

    Meira, C.R.; Purquerio, B.M.; Fortulan, C.A., E-mail: camilameira@sc.usp.br [Universidade de Sao Paulo (USP), Sao Carlos, SP (Brazil). Escola de Engenharia; Braga, F.J.C. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    Submicron bovine hydroxyapatite was obtained for rapid prototyping. Hydroxyapatite structure originated from bovine mineral bone has great importance among the biomaterials and biocompatibility due to its great similarity with the human bone structure. This study aims to obtain powder for manufacture by rapid prototyping of scaffolds. This technique manufacture requires highly reactive powders to compensate for the absence of pressure forming. Hydroxyapatite was milled in a ball mill and vibratory mill, and analyzed for their average equivalent spherical diameter and surface area. Test specimens were isostatically pressed at 100 MPa and machined into cylindrical test specimens. These specimens were sintered at several temperatures to determine the optimal sintering temperature based on densification and chemistry stability. In grinding ball mill was obtained particles of equivalent diameter of 0.74 micron in vibratory mill of 0.46 micrometers. An average flexural strength of 100 MPa and 99,8% of real density was attained for the sample sintered at 1300 deg C/2h, signaling potential for use in rapid prototyping. (author)

  9. IMPACT OF VIBRATORY AND ROTATIONAL SHOT PEENING ONTO SELECTED PROPERTIES OF TITANIUM ALLOY SURFACE LAYER

    Directory of Open Access Journals (Sweden)

    Kazimierz Zaleski

    2014-06-01

    Full Text Available This study presents the results of tests on impact of vibratory and rotational shot peening of the Ti6A12Mo2Cr titanium alloy onto the processed object surface roughness and surface layer microhardness. The external surfaces of ring-shaped samples were shot peened. The preceding process consisted of turning with a cubic boron nitride blade knife. Steel beads, having a diameter of 6 mm, were used as a processing medium. The variable parameters of shot peening were vibrator amplitude and shot peening time. The range of recommended technological parameters for vibratory and rotational shot peening was determined. As a result of shot peening, the surface roughness could be reduced by approximately 4 times and the surface layer could be hardened to the depth of approximately 0.4 mm.

  10. Vibratory-compacted (vipac/sphere-pac) nuclear fuels - a comparison with pelletized nuclear fuels

    Energy Technology Data Exchange (ETDEWEB)

    Chidester, K.; Rubin, J. [Los Alamos National Lab., NM (United States); Thompson, M

    2001-07-01

    In order to achieve the packing densities required for nuclear fuel stability, economy and performance, the fuel material must be densified. This has traditionally been performed by high-temperature sintering. (At one time, fuel densification was investigated using cold/hot swaging. However, this fabrication method has become uncommon.) Alternatively, fuel can be densified by vibratory compaction (VIPAC). During the late 1950's and into the 1970's, in the U.S., vibratory compaction fuel was fabricated and test irradiated to evaluate its applicability compared to the more traditional pelletized fuel for nuclear reactors. These activities were primarily focused on light water reactors (LWR) but some work was performed for fast reactors. This paper attempts to summarize these evaluations and proposes to reconsider VIPAC fuel for future use. (author)

  11. Vibratory sensory testing in acute compartment syndromes: a clinical and experimental study.

    Science.gov (United States)

    Phillips, J H; Mackinnon, S E; Beatty, S E; Dellon, A L; O'Brien, J P

    1987-05-01

    Invasive and noninvasive diagnostic testing was correlated in 11 patients with acute compartmental syndromes of the forearm. The excellent correlation between diminished perception of vibration and increasing compartmental pressure suggested that 256 cycle per second (cps) vibratory stimuli may be useful clinically in determining the appropriate time for surgical intervention in the acute compartmental syndrome. In 12 adult male volunteers, elevated compartment pressures were created in the anterior tibial compartment of the leg. A decrease in perception to 256 cycle per second (cps) vibratory stimulus was the earliest sensory abnormality to occur with elevated tissue compartment pressures. Analysis of variance showed significantly that 256-cps vibration was the most reliable and earliest sensory modality to change at pressures of 35 to 40 mmHg. These clinical and experimental findings support the use of the 256-cps tuning fork as a noninvasive diagnostic test in the evaluation of the patient with suspected acute compartment syndrome.

  12. Impact of interferometer optical path difference speed profile on the Fourier-transform-spectrometry-derived spectrum of a telecommunications signal.

    Science.gov (United States)

    Krause, Katie M; Genest, Jerome

    2006-07-01

    The impact of the interferometer optical path difference (OPD) speed profile on the spectrum, derived through the use of Fourier-transform spectrometry (FTS), of a synchronous optical network (SONET) signal is found. The SONET signal carries high-speed data traffic. It also may be modulated by low-frequency intensity or frequency modulation. It is found that the SONET header, high-speed data traffic and low-frequency modulation all manifest themselves as artifacts in the FTS-derived spectrum of the SONET signal. It is shown that a nonconstant OPD speed profile can smooth out these artifacts, making it unlikely that they will be mistaken for carrier signal peaks. However, it is found that smoothing out these artifacts lessens the achievable dynamic range of the FTS instrument in the frequency range of interest, the International Telecommunications Union common (C) and long (L) bands.

  13. Theoretical and experimental study of the transport of granular materials by inclined vibratory conveyors

    OpenAIRE

    Sloot, E.M.; Kruyt, Nicolaas P.

    1996-01-01

    A theoretical and experimental study was made of the conveying speed with which granular materials are transported by vibratory conveyors. The basic assumption made is that the layer of granular material can be considered as a point mass. The theory incorporates rest, slide, and flight phases of the material. Although the emphasis of this study is on the effect of the inclination (and declination) of the conveyor on the conveying speed, the effects of throw number, friction coefficient and vi...

  14. Histamine Derived from Probiotic Lactobacillus reuteri Suppresses TNF via Modulation of PKA and ERK Signaling

    Science.gov (United States)

    Thomas, Carissa M.; Hong, Teresa; van Pijkeren, Jan Peter; Hemarajata, Peera; Trinh, Dan V.; Hu, Weidong; Britton, Robert A.; Kalkum, Markus; Versalovic, James

    2012-01-01

    Beneficial microbes and probiotic species, such as Lactobacillus reuteri, produce biologically active compounds that can modulate host mucosal immunity. Previously, immunomodulatory factors secreted by L. reuteri ATCC PTA 6475 were unknown. A combined metabolomics and bacterial genetics strategy was utilized to identify small compound(s) produced by L. reuteri that were TNF-inhibitory. Hydrophilic interaction liquid chromatography-high performance liquid chromatography (HILIC-HPLC) separation isolated TNF-inhibitory compounds, and HILIC-HPLC fraction composition was determined by NMR and mass spectrometry analyses. Histamine was identified and quantified in TNF-inhibitory HILIC-HPLC fractions. Histamine is produced from L-histidine via histidine decarboxylase by some fermentative bacteria including lactobacilli. Targeted mutagenesis of each gene present in the histidine decarboxylase gene cluster in L. reuteri 6475 demonstrated the involvement of histidine decarboxylase pyruvoyl type A (hdcA), histidine/histamine antiporter (hdcP), and hdcB in production of the TNF-inhibitory factor. The mechanism of TNF inhibition by L. reuteri-derived histamine was investigated using Toll-like receptor 2 (TLR2)-activated human monocytoid cells. Bacterial histamine suppressed TNF production via activation of the H2 receptor. Histamine from L. reuteri 6475 stimulated increased levels of cAMP, which inhibited downstream MEK/ERK MAPK signaling via protein kinase A (PKA) and resulted in suppression of TNF production by transcriptional regulation. In summary, a component of the gut microbiome, L. reuteri, is able to convert a dietary component, L-histidine, into an immunoregulatory signal, histamine, which suppresses pro-inflammatory TNF production. The identification of bacterial bioactive metabolites and their corresponding mechanisms of action with respect to immunomodulation may lead to improved anti-inflammatory strategies for chronic immune-mediated diseases. PMID:22384111

  15. Histamine derived from probiotic Lactobacillus reuteri suppresses TNF via modulation of PKA and ERK signaling.

    Directory of Open Access Journals (Sweden)

    Carissa M Thomas

    Full Text Available Beneficial microbes and probiotic species, such as Lactobacillus reuteri, produce biologically active compounds that can modulate host mucosal immunity. Previously, immunomodulatory factors secreted by L. reuteri ATCC PTA 6475 were unknown. A combined metabolomics and bacterial genetics strategy was utilized to identify small compound(s produced by L. reuteri that were TNF-inhibitory. Hydrophilic interaction liquid chromatography-high performance liquid chromatography (HILIC-HPLC separation isolated TNF-inhibitory compounds, and HILIC-HPLC fraction composition was determined by NMR and mass spectrometry analyses. Histamine was identified and quantified in TNF-inhibitory HILIC-HPLC fractions. Histamine is produced from L-histidine via histidine decarboxylase by some fermentative bacteria including lactobacilli. Targeted mutagenesis of each gene present in the histidine decarboxylase gene cluster in L. reuteri 6475 demonstrated the involvement of histidine decarboxylase pyruvoyl type A (hdcA, histidine/histamine antiporter (hdcP, and hdcB in production of the TNF-inhibitory factor. The mechanism of TNF inhibition by L. reuteri-derived histamine was investigated using Toll-like receptor 2 (TLR2-activated human monocytoid cells. Bacterial histamine suppressed TNF production via activation of the H(2 receptor. Histamine from L. reuteri 6475 stimulated increased levels of cAMP, which inhibited downstream MEK/ERK MAPK signaling via protein kinase A (PKA and resulted in suppression of TNF production by transcriptional regulation. In summary, a component of the gut microbiome, L. reuteri, is able to convert a dietary component, L-histidine, into an immunoregulatory signal, histamine, which suppresses pro-inflammatory TNF production. The identification of bacterial bioactive metabolites and their corresponding mechanisms of action with respect to immunomodulation may lead to improved anti-inflammatory strategies for chronic immune-mediated diseases.

  16. Analyzing Signal Attenuation in PFG Anomalous Diffusion via a Modified Gaussian Phase Distribution Approximation Based on Fractal Derivative Model

    CERN Document Server

    Lin, Guoxing

    2016-01-01

    Pulsed field gradient (PFG) has been increasingly employed to study anomalous diffusions in Nuclear Magnetic Resonance (NMR) and Magnetic Resonance Imaging (MRI). However, the analysis of PFG anomalous diffusion is complicated. In this paper, a fractal derivative model based modified Gaussian phase distribution method is proposed to describe PFG anomalous diffusion. By using the phase distribution obtained from the effective phase shift diffusion method based on fractal derivatives, and employing some of the traditional Gaussian phase distribution approximation techniques, a general signal attenuation expression for free fractional diffusion is derived. This expression describes a stretched exponential function based attenuation, which is distinct from both the exponential attenuation for normal diffusion obtained from conventional Gaussian phase distribution approximation, and the Mittag-Leffler function based attenuation for anomalous diffusion obtained from fractional derivative. The obtained signal attenu...

  17. RAG1 core and V(DJ recombination signal sequences were derived from Transib transposons.

    Directory of Open Access Journals (Sweden)

    Vladimir V Kapitonov

    2005-06-01

    Full Text Available The V(DJ recombination reaction in jawed vertebrates is catalyzed by the RAG1 and RAG2 proteins, which are believed to have emerged approximately 500 million years ago from transposon-encoded proteins. Yet no transposase sequence similar to RAG1 or RAG2 has been found. Here we show that the approximately 600-amino acid "core" region of RAG1 required for its catalytic activity is significantly similar to the transposase encoded by DNA transposons that belong to the Transib superfamily. This superfamily was discovered recently based on computational analysis of the fruit fly and African malaria mosquito genomes. Transib transposons also are present in the genomes of sea urchin, yellow fever mosquito, silkworm, dog hookworm, hydra, and soybean rust. We demonstrate that recombination signal sequences (RSSs were derived from terminal inverted repeats of an ancient Transib transposon. Furthermore, the critical DDE catalytic triad of RAG1 is shared with the Transib transposase as part of conserved motifs. We also studied several divergent proteins encoded by the sea urchin and lancelet genomes that are 25%-30% identical to the RAG1 N-terminal domain and the RAG1 core. Our results provide the first direct evidence linking RAG1 and RSSs to a specific superfamily of DNA transposons and indicate that the V(DJ machinery evolved from transposons. We propose that only the RAG1 core was derived from the Transib transposase, whereas the N-terminal domain was assembled from separate proteins of unknown function that may still be active in sea urchin, lancelet, hydra, and starlet sea anemone. We also suggest that the RAG2 protein was not encoded by ancient Transib transposons but emerged in jawed vertebrates as a counterpart of RAG1 necessary for the V(DJ recombination reaction.

  18. Loss of signalling via Gα13 in germinal centre B-cell-derived lymphoma.

    Science.gov (United States)

    Muppidi, Jagan R; Schmitz, Roland; Green, Jesse A; Xiao, Wenming; Larsen, Adrien B; Braun, Sterling E; An, Jinping; Xu, Ying; Rosenwald, Andreas; Ott, German; Gascoyne, Randy D; Rimsza, Lisa M; Campo, Elias; Jaffe, Elaine S; Delabie, Jan; Smeland, Erlend B; Braziel, Rita M; Tubbs, Raymond R; Cook, J R; Weisenburger, Dennis D; Chan, Wing C; Vaidehi, Nagarajan; Staudt, Louis M; Cyster, Jason G

    2014-12-11

    Germinal centre B-cell-like diffuse large B-cell lymphoma (GCB-DLBCL) is a common malignancy, yet the signalling pathways that are deregulated and the factors leading to its systemic dissemination are poorly defined. Work in mice showed that sphingosine-1-phosphate receptor-2 (S1PR2), a Gα12 and Gα13 coupled receptor, promotes growth regulation and local confinement of germinal centre B cells. Recent deep sequencing studies of GCB-DLBCL have revealed mutations in many genes in this cancer, including in GNA13 (encoding Gα13) and S1PR2 (refs 5,6, 7). Here we show, using in vitro and in vivo assays, that GCB-DLBCL-associated mutations occurring in S1PR2 frequently disrupt the receptor's Akt and migration inhibitory functions. Gα13-deficient mouse germinal centre B cells and human GCB-DLBCL cells were unable to suppress pAkt and migration in response to S1P, and Gα13-deficient mice developed germinal centre B-cell-derived lymphoma. Germinal centre B cells, unlike most lymphocytes, are tightly confined in lymphoid organs and do not recirculate. Remarkably, deficiency in Gα13, but not S1PR2, led to germinal centre B-cell dissemination into lymph and blood. GCB-DLBCL cell lines frequently carried mutations in the Gα13 effector ARHGEF1, and Arhgef1 deficiency also led to germinal centre B-cell dissemination. The incomplete phenocopy of Gα13- and S1PR2 deficiency led us to discover that P2RY8, an orphan receptor that is mutated in GCB-DLBCL and another germinal centre B-cell-derived malignancy, Burkitt's lymphoma, also represses germinal centre B-cell growth and promotes confinement via Gα13. These findings identify a Gα13-dependent pathway that exerts dual actions in suppressing growth and blocking dissemination of germinal centre B cells that is frequently disrupted in germinal centre B-cell-derived lymphoma.

  19. Pentoxifylline Inhibits WNT Signalling in β-Cateninhigh Patient-Derived Melanoma Cell Populations.

    Directory of Open Access Journals (Sweden)

    Beata Talar

    Full Text Available The heterogeneity of melanoma needs to be addressed and combination therapies seem to be necessary to overcome intrinsic and acquired resistance to newly developed immunotherapies and targeted therapies. Although the role of WNT/β-catenin pathway in melanoma was early demonstrated, its contribution to the lack of the melanoma patient response to treatment was only recently recognized. Using patient-derived melanoma cell populations, we investigated the influence of pentoxifylline on melanoma cells with either high or low expression of β-catenin.Our results indicate that pentoxifylline inhibits the activity of the canonical WNT pathway in melanoma cell populations with high basal activity of this signalling. This is supported by lowered overall activity of transcription factors TCF/LEF and reduced nuclear localisation of active β-catenin. Moreover, treatment of β-cateninhigh melanoma cell populations with pentoxifylline induces downregulation of genes that are targets of the WNT/β-catenin pathway including connective tissue growth factor (CTGF and microphthalmia-associated transcription factor (MITF-M, a melanocyte- and melanoma cell-specific regulator.These results suggest that pentoxifylline, a drug approved by the FDA in the treatment of peripheral arterial disease, might be tested in a subset of melanoma patients with elevated activity of β-catenin. This pharmaceutical might be tested as an adjuvant drug in combination therapies when the response to immunotherapy is prevented by high activity of the WNT/β-catenin pathway.

  20. Signal-to-noise ratios of the auditory steady-state response from fifty-five EEG derivations in adults.

    NARCIS (Netherlands)

    Reijden, C.S. van der; Mens, L.H.M.; Snik, A.F.M.

    2004-01-01

    The Auditory Steady-State Response (ASSR) was recorded in 20 awake adults with normal hearing on ten EEG channels simultaneously to find derivations with the best signal-to-noise ratios (SNRs). Stimuli were 20% frequency modulated tones of 0.5 and 2 kHz at 20 dB SL, 100% amplitude modulated at 90 or

  1. Wnt/β-catenin-signaling and the formation of Müller glia-derived progenitors in the chick retina.

    Science.gov (United States)

    Gallina, Donika; Palazzo, Isabella; Steffenson, Lillia; Todd, Levi; Fischer, Andy J

    2016-09-01

    Müller glia can be stimulated to de-differentiate, proliferate, and form Müller glia-derived progenitor cells (MGPCs) that are capable of producing retinal neurons. The signaling pathways that influence the de-differentiation of mature Müller glia and proliferation of MGPCs may include the Wnt-pathway. The purpose of this study was to investigate how Wnt-signaling influences the formation of MGPCs in the chick retina in vivo. In NMDA-damaged retinas where MGPCs are known to form, we find dynamic changes in retinal levels of potential readouts of Wnt-signaling, including dkk1, dkk3, axin2, c-myc, tcf-1, and cd44. We find accumulations of nuclear β-catenin in MGPCs that peaks at 3 days and rapidly declines by 5 days after NMDA-treatment. Inhibition of Wnt-signaling with XAV939 in damaged retinas suppressed the formation of MGPCs, increased expression of ascl1a and decreased hes5, but had no effect upon the differentiation of progeny produced by MGPCs. Activation of Wnt-signaling, with GSK3β-inhibitors, in the absence of retinal damage, failed to stimulate the formation of MGPCs, whereas activation of Wnt-signaling in damaged retinas stimulated the formation of MGPCs. In the absence of retinal damage, FGF2/MAPK-signaling stimulated the formation of MGPCs by activating a signaling network that includes Wnt/β-catenin. In FGF2-treated retinas, inhibition of Wnt-signaling reduced numbers of proliferating MGPCs, whereas activation of Wnt-signaling failed to influence the formation of proliferating MGPCs. Our findings indicate that Wnt-signaling is part of a network initiated by FGF2/MAPK or retinal damage, and activation of canonical Wnt-signaling is required for the formation of proliferating MGPCs. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 983-1002, 2016. © 2015 Wiley Periodicals, Inc.

  2. Compensation of Imperfections for Vibratory Gyroscope Systems Using State Observers

    Directory of Open Access Journals (Sweden)

    Chien-Yu CHI

    2009-08-01

    Full Text Available This paper presents a novel approach that can compensate errors resulting from the imperfections of mechanical structures and interface circuits for MEMS gyroscope systems. Different from most of existing researches on gyroscopes wherein the mechanical structure and interface circuit are either assumed to be ideal or optimized individually, this approach uses state estimation techniques to compensate all those errors and to obtain correct angular rates in real time. The mechanical structure errors discussed in this paper may come from structure designs and fabrication imperfections. The interface circuit errors include: mismatch of differential capacitors, parasitic capacitance, offset voltage of operation amplifiers, and circuit noise. Simulation results indicates that, with the presence of those errors and a signal-to-noise ratio around 20, the proposed method can measure time-varying angular rates with a bandwidth up to 30 Hz and a sensing accuracy of 1×10-2 rad/sec.

  3. Distribution and Variability of Satellite-Derived Signals of Isolated Convection Initiation Events Over Central Eastern China

    Science.gov (United States)

    Huang, Yipeng; Meng, Zhiyong; Li, Jing; Li, Wanbiao; Bai, Lanqiang; Zhang, Murong; Wang, Xi

    2017-11-01

    This study combined measurements from the Chinese operational geostationary satellite Fengyun-2E (FY-2E) and ground-based weather radars to conduct a statistical survey of isolated convection initiation (CI) over central eastern China (CEC). The convective environment in CEC is modulated by the complex topography and monsoon climate. From May to August 2010, a total of 1,630 isolated CI signals were derived from FY-2E using a semiautomated method. The formation of these satellite-derived CI signals peaks in the early afternoon and occurs with high frequency in areas with remarkable terrain inhomogeneity (e.g., mountain, water, and mountain-water areas). The high signal frequency areas shift from northwest CEC (dry, high altitude) in early summer to southeast CEC (humid, low altitude) in midsummer along with an increasing monthly mean frequency. The satellite-derived CI signals tend to have longer lead times (the time difference between satellite-derived signal formation and radar-based CI) in the late morning and afternoon than in the early morning and night. During the early morning and night, the distinction between cloud top signatures and background terrestrial radiation becomes less apparent, resulting in delayed identification of the signals and thus short and even negative lead times. A decline in the lead time is observed from May to August, likely due to the increasing cloud growth rate and warm-rain processes. Results show increasing lead times with increasing landscape elevation, likely due to more warm-rain processes over the coastal sea and plain, along with a decreasing cloud growth rate from hill and mountain to the plateau.

  4. Adenosine signaling promotes neuronal, catecholaminergic differentiation of primary neural crest cells and CNS-derived CAD cells.

    Science.gov (United States)

    Bilodeau, Matthew L; Ji, Ming; Paris, Maryline; Andrisani, Ourania M

    2005-07-01

    In neural crest (NC) cultures cAMP signaling is an instructive signal in catecholaminergic, sympathoadrenal cell development. However, the extracellular signals activating the cAMP pathway during NC cell development have not been identified. We demonstrate that in avian NC cultures, evidenced by tyrosine hydroxylase expression and catecholamine biosynthesis, adenosine and not adrenergic signaling, together with BMP2, promotes sympathoadrenal cell development. In NC cultures, addition of the adenosine receptor agonist NECA in the presence of BMP2 promotes sympathoadrenal cell development, whereas the antagonist CGS 15943 or the adenosine degrading enzyme adenosine deaminase (ADA) suppresses TH expression. Importantly, NC cells express A2A and A2B receptors which couple with Gsalpha increasing intracellular cAMP. Employing the CNS-derived catecholaminergic CAD cell line, we also demonstrate that neuronal differentiation mediated by serum withdrawal is further enhanced by treatment with IBMX, a cAMP-elevating agent, or the adenosine receptor agonist NECA, acting via cAMP. By contrast, the adenosine receptor antagonist CGS 15943 or the adenosine degrading enzyme ADA inhibits CAD cell neuronal differentiation mediated by serum withdrawal. These results support that adenosine is a physiological signal in neuronal differentiation of the CNS-derived catecholaminergic CAD cell line and suggest that adenosine signaling is involved in NC cell development in vivo.

  5. Distinct effectors of platelet-derived growth factor receptor-α signaling are required for cell survival during embryogenesis

    Science.gov (United States)

    Van Stry, Melanie; Kazlauskas, Andrius; Schreiber, Stuart L.; Symes, Karen

    2005-01-01

    Platelet-derived growth factor receptor (PDGFR) signaling is essential for normal embryonic development in many organisms, including frog, mouse, zebrafish, and sea urchin. The mode of action of PDGFR signaling during early development is poorly understood, however, mostly because inhibition of signaling through either the PDGFRα or PDGFRβ is embryonic lethal. In Xenopus embryos, disruption of PDGFRα signaling causes migrating anterior mesoderm cells to lose direction and undergo apoptosis through the mitochondrial pathway. To understand the mechanism of PDGFRα function in this process, we have analyzed all known effector-binding sites in vivo. By using a chemical inducer of dimerization to activate chimera PDGFRαs, we have identified a role for phospholipase Cγ (PLCγ) in protecting cells from death. PDGFRα-mediated cell survival requires PLCγ and phosphatidylinositol 3-kinase signaling, and that PDGFRα with binding sites for these two signaling factors is sufficient for this activity. Other effectors of PDGFRα signaling, Shf, SHP-2, and Crk, are not required for this process. Thus, our findings show that PDGFRα signaling through PLCγ and phosphatidylinositol 3-kinase has a protective role in preventing apoptosis in early development. Furthermore, we demonstrate that small molecule inducers of dimerization provide a powerful system to manipulate receptor function in developing embryos. PMID:15919820

  6. Distinct effectors of platelet-derived growth factor receptor-alpha signaling are required for cell survival during embryogenesis.

    Science.gov (United States)

    Van Stry, Melanie; Kazlauskas, Andrius; Schreiber, Stuart L; Symes, Karen

    2005-06-07

    Platelet-derived growth factor receptor (PDGFR) signaling is essential for normal embryonic development in many organisms, including frog, mouse, zebrafish, and sea urchin. The mode of action of PDGFR signaling during early development is poorly understood, however, mostly because inhibition of signaling through either the PDGFRalpha or PDGFRbeta is embryonic lethal. In Xenopus embryos, disruption of PDGFRalpha signaling causes migrating anterior mesoderm cells to lose direction and undergo apoptosis through the mitochondrial pathway. To understand the mechanism of PDGFRalpha function in this process, we have analyzed all known effector-binding sites in vivo. By using a chemical inducer of dimerization to activate chimera PDGFRalphas, we have identified a role for phospholipase Cgamma (PLCgamma) in protecting cells from death. PDGFRalpha-mediated cell survival requires PLCgamma and phosphatidylinositol 3-kinase signaling, and that PDGFRalpha with binding sites for these two signaling factors is sufficient for this activity. Other effectors of PDGFRalpha signaling, Shf, SHP-2, and Crk, are not required for this process. Thus, our findings show that PDGFRalpha signaling through PLCgamma and phosphatidylinositol 3-kinase has a protective role in preventing apoptosis in early development. Furthermore, we demonstrate that small molecule inducers of dimerization provide a powerful system to manipulate receptor function in developing embryos.

  7. In vitro osteoinductive effects of hydroxycholesterol on human adipose-derived stem cells are mediated through the hedgehog signaling pathway.

    Science.gov (United States)

    Yalom, Anisa; Hokugo, Akishige; Sorice, Sarah; Li, Andrew; Segovia Aguilar, Luis A; Zuk, Patricia; Jarrahy, Reza

    2014-11-01

    Human adipose-derived stem cells have been identified as a potential source of cells for use in bone tissue engineering because of their ready availability, ease of harvest, and susceptibility to osteogenic induction. The authors have previously demonstrated the ability of an osteogenic molecule called hydroxycholesterol, an oxidative derivative of cholesterol, to induce osteogenic differentiation in pluripotent murine and rabbit bone marrow stromal cells. In this study, the authors examine the ability of hydroxycholesterol to induce osteogenesis in human adipose-derived stem cells. Human adipose-derived stem cells were isolated from raw human lipoaspirates through standard isolation and expansion of the stromal vascular fraction. Cells were plated onto tissue culture plates in control medium and harvested between passages 2 and 3, incubated with conventional osteogenic media, and treated with various concentrations (1, 5, and 10 μM) of the 20(S) analogue of hydroxycholesterol. Evaluation of cellular osteogenic activity was performed. The role of the hedgehog signaling pathway in hydroxycholesterol-mediated osteogenesis was evaluated by hedgehog inhibition assays. Alkaline phosphatase activity, bone-related gene expression, and mineralization were all significantly increased in cultures of human adipose-derived stem cells treated with 5 μM of 20(S)-hydroxycholesterol relative to controls. In addition, induction of hydroxycholesterol-mediated osteogenesis was mitigated by the addition of the hedgehog pathway inhibitor to cell cultures, implicating the hedgehog signaling pathway in the osteogenic mechanism on human adipose-derived stem cells by hydroxycholesterol. These in vitro studies demonstrate that hydroxycholesterol exerts an osteoinductive influence on human adipose-derived stem cells and that these effects are mediated at least in part through the hedgehog signaling pathway.

  8. Vibratory stimulation and rectal probe electroejaculation as therapy for patients with spinal cord injury: semen parameters and pregnancy rates.

    Science.gov (United States)

    Nehra, A; Werner, M A; Bastuba, M; Title, C; Oates, R D

    1996-02-01

    The conception rate of patients with spinal cord injuries following penile vibratory stimulation and rectal probe electroejaculation in conjunction with self-insemination, intrauterine insemination or assisted reproductive technique is poorly documented. We reviewed our success rates with penile vibratory stimulation and rectal probe electroejaculation, and the pregnancy rates achieved with self-insemination, intrauterine insemination and assisted reproductive techniques. A total of 78 consecutive patients with spinal cord injuries had a complete neurological examination and was treated initially with penile vibratory stimulation. If unsuccessful, rectal probe electroejaculation was performed to obtain an ejaculate. The ejaculate was then used with self-insemination, intrauterine insemination or assisted reproductive techniques and pregnancies were monitored. Vibratory stimulation was successful in 20 of 37 patients (54%) with a cervical lesion, 14 of 26 (54%) with a lesion at or above T10 and none of 15 when the lesion was below T10. All patients except 2 who elected followup rectal probe electroejaculation had antegrade or retrograde ejaculate. Six patients (7.7%) with extremely poor semen quality were not candidates for assisted fertilization. Of 27 couples who attempted conception 17 were successful (5 self-insemination, 5 intrauterine insemination and 7 assisted reproductive techniques). Penile vibratory stimulation should be used as first line therapy in patients with lesions above T10 while rectal probe electroejaculation should be considered as a second option. Motivated patients can achieve success with self-insemination, intrauterine insemination and assisted reproductive techniques.

  9. RSPO3-LGR4 Regulates Osteogenic Differentiation Of Human Adipose-Derived Stem Cells Via ERK/FGF Signalling.

    Science.gov (United States)

    Zhang, Min; Zhang, Ping; Liu, Yunsong; Lv, Longwei; Zhang, Xiao; Liu, Hao; Zhou, Yongsheng

    2017-02-21

    The four R-spondins (RSPOs) and their three related receptors, LGR4, 5 and 6, have emerged as a major ligand-receptor system with critical roles in development and stem cell survival. However, the exact roles of the RSPO-LGR system in osteogenesis remain largely unknown. In the present study, we showed that RSPO3-shRNA increased the osteogenic potential of human adipose-derived stem cells (hASCs) significantly. Mechanistically, we demonstrated that RSPO3 is a negative regulator of ERK/FGF signalling. We confirmed that inhibition of the ERK1/2 signalling pathway blocked osteogenic differentiation in hASCs, and the increased osteogenic capacity observed after RSPO3 knockdown in hASCs was reversed by inhibition of ERK signalling. Further, silencing of LGR4 inhibited the activity of ERK signalling and osteogenic differentiation of hASCs. Most importantly, we found that loss of LGR4 abrogated RSPO3-regulated osteogenesis and RSPO3-induced ERK1/2 signalling inhibition. Collectively, our data show that ERK signalling works downstream of LGR4 and RSPO3 regulates osteoblastic differentiation of hASCs possibly via the LGR4-ERK signalling.

  10. The blockage of Notch signalling promoted the generation of polymorphonuclear myeloid-derived suppressor cells with lower immunosuppression.

    Science.gov (United States)

    Wang, Shu-Hong; Lu, Qing-Yang; Guo, Ya-Huan; Song, Yuan-Yuan; Liu, Pei-Jun; Wang, Yao-Chun

    2016-11-01

    Myeloid-derived suppressor cells (MDSCs) mostly consisting of polymorphonuclear (PMN)-MDSCs and mononuclear MDSCs have been considered to play critical roles in immunosuppression, angiogenesis, invasion and metastases of various tumours. However, it is still unclear the regulated mechanisms underlying the generation and immunosuppression of two major MDSC subsets. Here, we report Notch signalling was inhibited significantly in tumour-bearing mouse MDSCs, in which PMN-MDSCs were the major population. MDSCs without recombination signal binding protein-Jк (RBP-J), the critical transcription factor mediating signalling from all four mammalian Notch receptors, reduced their ability of inhibiting the proliferation and activation of allogenic T cells. RBP-J-deficient MDSCs could not down-regulate the expression of co-stimulation molecules on dendritic cells (DCs). The antigen presentation capacity of DCs co-cultured with RBP-J-deficient MDSCs was not impaired in contrast to controls. Moreover, we show the blockage of Notch signalling could improve the generation of PMN-MDSCs but inhibit the production of mononuclear MDSCs both in vitro and in vivo. Stat3 pathway was suppressed in MDSCs blocked Notch signalling and Stat3 activation by IL-6 could reverse the phenotype and immunosuppression of Notch signalling-deficient MDSCs. Therefore, targeting Notch signalling may be an effective therapeutic strategy in tumour therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Resolution of type 2 diabetes following gastric bypass surgery: involvement of gut-derived glucagon and glucagonotropic signalling?

    DEFF Research Database (Denmark)

    Knop, Filip Krag

    2009-01-01

    Certain types of bariatric surgical procedures have proved not only to be effective with regard to treating obesity, but they also seem to be associated with endocrine changes which independently of weight loss give rise to remission of type 2 diabetes. Currently, it is speculated that surgical re......-derived glucagonotropic signalling as putative diabetogenic signals of the foregut hypothesis. In the present paper the hypotheses describing the glucose-lowering mechanisms of bariatric surgical procedures sharing the common feature of a bypass of the duodenum and the proximal jejunum are outlined and a possible role...

  12. Research on Bell-Shaped Vibratory Angular Rate Gyro’s Character of Resonator

    Directory of Open Access Journals (Sweden)

    Hong Liu

    2013-04-01

    Full Text Available Bell-shaped vibratory angular rate gyro (abbreviated as BVG is a new type Coriolis vibratory gyro that was inspired by Chinese traditional clocks. The resonator fuses based on a variable thickness axisymmetric multicurved surface shell. Its characteristics can directly influence the performance of BVG. The BVG structure not only has capabilities of bearing high overload, high impact and, compared with the tuning fork, vibrating beam, shell and a comb structure, but also a higher frequency to overcome the influence of the disturbance of the exterior environment than the same sized hemispherical resonator gyroscope (HRG and the traditional cylinder vibratory gyroscope. It can be widely applied in high dynamic low precision angular rate measurement occasions. The main work is as follows: the issue mainly analyzes the structure and basic principle, and investigates the bell-shaped resonator’s mathematical model. The reasonable structural parameters are obtained from finite element analysis and an intelligent platform. Using the current solid vibration gyro theory analyzes the structural characteristics and principles of BVG. The bell-shaped resonator is simplified as a paraboloid of the revolution mechanical model, which has a fixed closed end and a free opened end. It obtains the natural frequency and vibration modes based on the theory of elasticity. The structural parameters are obtained from the orthogonal method by the research on the structural parameters of the resonator analysis. It obtains the modal analysis, stress analysis and impact analysis with the chosen parameters. Finally, using the turntable experiment verifies the gyro effect of the BVG.

  13. Analyzing signal attenuation in PFG anomalous diffusion via a modified Gaussian phase distribution approximation based on fractal derivative model

    Science.gov (United States)

    Lin, Guoxing

    2017-02-01

    Pulsed field gradient (PFG) technique is a noninvasive tool, and has been increasingly employed to study anomalous diffusions in Nuclear Magnetic Resonance (NMR) and Magnetic Resonance Imaging (MRI). However, the analysis of PFG anomalous diffusion is much more complicated than normal diffusion. In this paper, a fractal derivative model based modified Gaussian phase distribution method is proposed to describe PFG anomalous diffusion. By using the phase distribution obtained from the effective phase shift diffusion method based on fractal derivatives, and employing some of the traditional Gaussian phase distribution approximation techniques, a general signal attenuation expression for free fractional diffusion is derived. This expression describes a stretched exponential function based attenuation, which is distinct from both the exponential attenuation for normal diffusion obtained from conventional Gaussian phase distribution approximation, and the Mittag-Leffler function based attenuation for anomalous diffusion obtained from fractional derivative. The obtained signal attenuation expression can analyze the finite gradient pulse width (FGPW) effect. Additionally, it can generally be applied to all three types of PFG fractional diffusions classified based on time derivative order α and space derivative order β. These three types of fractional diffusions include time-fractional diffusion with { 0 < α ≤ 2 , β = 2 } , space-fractional diffusion with { α = 1 , 0 < β ≤ 2 } , and general fractional diffusion with { 0 < α , β ≤ 2 } . The results in this paper are consistent with reported results based on effective phase shift diffusion equation method and instantaneous signal attenuation method. This method provides a new, convenient approximation formalism for analyzing PFG anomalous diffusion experiments. The expression that can simultaneously interpret general fractional diffusion and FGPW effect could be especially important in PFG MRI, where the narrow

  14. Identification of the 3D Vibratory Motion of a Rigid Body by Accelerometer Measurements

    Directory of Open Access Journals (Sweden)

    Francesca Di Puccio

    2004-01-01

    Full Text Available The identification of the motion of a rigid body by means of linear accelerometers is a problem already investigated by many researchers, but still debated. The optimisation of the number and placement of accelerometers is also another important aspect of the problem. In this study, an experimental procedure is proposed and applied to identify the rigid-body vibratory motion of the steering wheel of a sporting car, by means of six linear accelerometers. Some numerical simulations for investigating possible errors are also presented.

  15. Fundamental understanding, prediction and validation of rotor vibratory loads in steady-level flight

    Science.gov (United States)

    Datta, Anubhav

    This work isolates the physics of aerodynamics and structural dynamics from the helicopter rotor aeromechanics problem, investigates them separately, identifies the prediction deficiencies in each, improves upon them, and couples them back together. The objective is to develop a comprehensive analysis capability for accurate and consistent prediction of rotor vibratory loads in steady level flight. The rotor vibratory loads are the dominant source of helicopter vibration. There are two critical vibration regimes for helicopters in steady level flight: (1) low speed transition and (2) high speed forward flight. The mechanism of rotor vibration at low speed transition is well understood---inter-twinning of blade tip vortices below the rotor disk. The mechanism of rotor vibration at high speed is not clear. The focus in this research is on high speed flight. The goal is to understand the key mechanisms involved and accurately model them. Measured lift, chord force, pitching moment and damper force from the UH-60A Flight Test Program are used to predict, validate and refine the rotor structural dynamics. The prediction errors originate entirely from structural modeling. Once validated, the resultant blade deformations are used to predict and validate aerodynamics. Air loads are calculated using a table look up based unsteady lifting-line model and compared with predictions from a 3-dimensional unsteady CFD model. Both Navier-Stokes and Euler predictions are studied. (Abstract shortened by UMI.) The 3D Navier-Stokes CFD analysis is then consistently coupled with a rotor comprehensive analysis to improve prediction of rotor vibratory loads at high speed. The CFD-comprehensive code coupling is achieved using a loose coupling methodology. The CFD analysis significantly improves section pitching moment prediction near the blade tip, because it captures the steady and unsteady 3D transonic effects. Accurate pitching moments drive elastic twist deformations which together

  16. Cavitation Erosion Tests Performed by Indirect Vibratory Method on Stainless Steel Welded Samples with Hardened Surface

    Directory of Open Access Journals (Sweden)

    Marian-Dumitru Nedeloni

    2012-09-01

    Full Text Available The paper presents the results of cavitation erosion tests performed on two types of samples. The materials of the samples are frequently used for manufacturing and repairs of the hydro turbines components submitted to cavitation. The first sample was made by welding of an austenitic stainless steel on austenito-feritic base material. The second sample was made similarly with the first but with a martensitic base material. After the welding processes, on both samples was applied a hardening treatment by surface peening. The cavitation erosion tests were performed on vibratory equipment using the indirect method with stationary specimen. The results show a good cavitation erosion resistance on both samples.

  17. Optimization of process parameters during vibratory welding technique using Taguchi's analysis

    OpenAIRE

    Singh, Pravin Kumar; Patel, D.; Prasad,S.B.

    2016-01-01

    With an aim to improve the mechanical properties of a weld joint, a new concept of vibratory setup has been designed which is capable to stir the molten weld pool before it solidifies during shielded metal arc welding (SMAW) operation. Mechanical vibration having resonance frequency of 300 Hz and amplitude of 0.5 mm was transferred to the molten weld pool of 6 mm thick mild steel butt-welded joints during the welding operation. The experimental work was conducted at various ranges of frequenc...

  18. Identification of elasticity modulus by vibratory analysis (Application to a natural composite: Aleppo pine wood

    Directory of Open Access Journals (Sweden)

    DAOUI Abdelhakim

    2018-01-01

    Full Text Available In this paper, we present a method for the determination of the elasticity modulus in the vibratory domain of materials. This approach is based on research and interpretation of the spectrum of natural frequencies resulting from natural vibrations based on the theory of elastic beams. The tests consist of classical tests of longitudinal vibrations of natural composite beams (Aleppo pine wood, long enough to observe some natural frequencies. This identification method showed a good correlation between the theoretical and experimental values, notably the evaluation of the modal parameter for the case of the resonant frequencies and the identification of the modulus of elasticity of the materials used.

  19. Penile vibratory stimulation and electroejaculation in the treatment of ejaculatory dysfunction.

    Science.gov (United States)

    Sønksen, Jens; Ohl, Dana A

    2002-12-01

    The purpose of this review is to present the current understanding of penile vibratory stimulation (PVS) and electroejaculation (EEJ) procedures and its clinical use in men with ejaculatory dysfunction. Unfortunately, the record of treating such individuals has been quite poor, but within recent years development and refinement of PVS and EEJ in men with spinal cord injury (SCI) has significantly enhanced the prospects for treatment of ejaculatory dysfunction. The majority of spinal cord injured men are not able to produce antegrade ejaculation by masturbation or sexual stimulation. However, approximately 80% of all spinal cord injured men with an intact ejaculatory reflex arc (above T10) can obtain antegrade ejaculation with PVS. Electroejaculation may be successful in obtaining ejaculate from men with all types of SCI, including men who do not have major components of the ejaculatory reflex arc. Because vibratory stimulation is very simple in use, non-invasive, it does not require anaesthesia and is preferred by the patients when compared with EEJ, PVS is recommended to be the first choice of treatment in spinal cord injured men. Furthermore, EEJ has been successfully used to induce ejaculation in men with multiple sclerosis and diabetic neuropathy. Any other conditions which affect the ejaculatory mechanism of the central and/or peripheral nervous system including surgical nerve injury may be treated successfully with EEJ. Finally, for sperm retrieval and sperm cryopreservation before intensive anticancer therapy in pubertal boys, PVS and EEJ have been successfully performed in patients who failed to obtain ejaculation by masturbation. Nearly all data concerning semen characteristics in men with ejaculatory dysfuntion originate from spinal cord injured men. Semen analyses demonstrate low sperm motility rates in the majority of spinal cord injured men. The data give evidence of a decline in spermatogenesis and motility of ejaculated spermatozoa shortly after (few

  20. Comparison of energy costs for different control laws of a vibratory robot

    Science.gov (United States)

    Golitsyna, Maria

    2017-01-01

    In the study there are introduced several control methods that maximize average velocity of the vibratory robot subject to several constraints. The robot is presented by a rigid box with a pendulum inside it. It can move forwards and backwards and there is a Coulomb friction between the box and the surface. In the paper it is not only shown the difference and advantages of proposed control laws but there is also done a comparison between efforts done by the motor that provides rotation of the pendulum for different control methods.

  1. Hh signaling regulates patterning and morphogenesis of the pharyngeal arch-derived skeleton.

    Science.gov (United States)

    Swartz, Mary E; Nguyen, Van; McCarthy, Neil Q; Eberhart, Johann K

    2012-09-01

    The proper function of the craniofacial skeleton requires the proper shaping of many individual skeletal elements. Neural crest cells generate much of the craniofacial skeleton and morphogenesis of skeletal elements occurs in transient, reiterated structures termed pharyngeal arches. The shape of individual elements depends upon intrinsic patterning within the neural crest as well as extrinsic signals to the neural crest from adjacent tissues within the arches. Hedgehog (Hh) signaling is known to play roles in craniofacial development, yet its involvement in intrinsic and extrinsic patterning of the craniofacial skeleton is still not well understood. Here, we show that morphogenetic movements of the pharyngeal arches and patterning of the neural crest require Hh signaling. Loss of Hh signaling, in smoothened (smo) mutants, disrupts the expression of some Dlx genes as well as other markers of dorsal/ventral patterning of the neural crest. Transplantation of wild-type neural crest cells into smo mutants rescues this defect, demonstrating that the neural crest requires reception of Hh signals for proper patterning. Despite the rescue, morphogenesis of the facial skeleton is not fully recovered. Through transplant analyses, we find two additional requirements for Hh signaling. The endoderm requires the reception of Hh signals for proper morphogenetic movements of the pharyngeal arches and the neural crest require the reception of Hh signaling for the activity of a reverse signal that maintains sonic hedgehog expression in the endoderm. Collectively, these results demonstrate that Hh signaling is essential to establish intrinsic and extrinsic patterning information for the craniofacial skeleton. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Analyzing signal attenuation in PFG anomalous diffusion via a non-Gaussian phase distribution approximation approach by fractional derivatives

    CERN Document Server

    Lin, Guoxing

    2016-01-01

    Anomalous diffusion exists widely in polymer and biological systems. Pulsed field gradient (PFG) techniques have been increasingly used to study anomalous diffusion in NMR and MRI. However, the interpretation of PFG anomalous diffusion is complicated. Moreover, there is not an exact signal attenuation expression based on fractional derivatives for PFG anomalous diffusion, which includes the finite gradient pulse width effect. In this paper, a new method, a Mainardi-Luchko-Pagnini (MLP) phase distribution approximation, is proposed to describe PFG fractional diffusion. MLP phase distribution is a non-Gaussian phase distribution. From the fractional diffusion equation based on fractional derivatives in both real space and phase space, the obtained probability distribution function is a MLP distribution. The MLP distribution leads to a Mittag-Leffler function based PFG signal attenuation rather than the exponential or stretched exponential attenuation that is obtained from a Gaussian phase distribution (GPD) und...

  3. Correction of gradient echo images for first and second order macroscopic signal dephasing using phase derivative mapping.

    Science.gov (United States)

    de Leeuw, H; Bakker, C J G

    2012-03-01

    Gradient echo techniques are often hampered by signal dephasing due to macroscopic phase perturbations because of system imperfections (shimming) or object induced perturbations of the magnetic field (hemorrhagic lesions, calcified tissue, air-tissue interfaces). Many techniques have been proposed to reduce the effects of macroscopic phase variations. Among these techniques are tuned pulse sequences, fitting techniques and reconstruction algorithms. These methods, however, suffer from one or more of the following drawbacks: they require longer acquisition times, require additional acquisitions, compensate only locally, can only be applied to multi-gradient echo data or may result in inaccurate results. In this work a generally applicable post-processing technique is presented to evaluate and compensate signal alterations invoked by first and second order macroscopic phase incoherences. In this technique, the derivatives of the signal phase are determined by applying the Fourier derivative theorem on the complex data. As a result, the phase derivatives are obtained without phase unwrapping and without compromising the resolution. The method is validated for single and multi-echo acquisitions by experiments on a co-axial cylinder phantom with known macroscopic field disturbances. The potential of the method is demonstrated on a multi-gradient echo acquisition on the head of a human volunteer. In general a first order correction is shown to be sufficient, however higher order correction is found to be beneficial near sharp transitions of the magnetic field. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Neural crest-derived mesenchymal cells require Wnt signaling for their development and drive invagination of the telencephalic midline.

    Directory of Open Access Journals (Sweden)

    Youngshik Choe

    Full Text Available Embryonic neural crest cells contribute to the development of the craniofacial mesenchyme, forebrain meninges and perivascular cells. In this study, we investigated the function of ß-catenin signaling in neural crest cells abutting the dorsal forebrain during development. In the absence of ß-catenin signaling, neural crest cells failed to expand in the interhemispheric region and produced ectopic smooth muscle cells instead of generating dermal and calvarial mesenchyme. In contrast, constitutive expression of stabilized ß-catenin in neural crest cells increased the number of mesenchymal lineage precursors suggesting that ß-catenin signaling is necessary for the expansion of neural crest-derived mesenchymal cells. Interestingly, the loss of neural crest-derived mesenchymal stem cells (MSCs leads to failure of telencephalic midline invagination and causes ventricular system defects. This study shows that ß-catenin signaling is required for the switch of neural crest cells to MSCs and mediates the expansion of MSCs to drive the formation of mesenchymal structures of the head. Furthermore, loss of these structures causes striking defects in forebrain morphogenesis.

  5. Endothelial cell-derived matrix promotes the metabolic functional maturation of hepatocyte via integrin-Src signalling.

    Science.gov (United States)

    Guo, Xinyue; Li, Weihong; Ma, Minghui; Lu, Xin; Zhang, Haiyan

    2017-11-01

    The extracellular matrix (ECM) microenvironment is involved in the regulation of hepatocyte phenotype and function. Recently, the cell-derived extracellular matrix has been proposed to represent the bioactive and biocompatible materials of the native ECM. Here, we show that the endothelial cell-derived matrix (EC matrix) promotes the metabolic maturation of human adipose stem cell-derived hepatocyte-like cells (hASC-HLCs) through the activation of the transcription factor forkhead box protein A2 (FOXA2) and the nuclear receptors hepatocyte nuclear factor 4 alpha (HNF4α) and pregnane X receptor (PXR). Reducing the fibronectin content in the EC matrix or silencing the expression of α5 integrin in the hASC-HLCs inhibited the effect of the EC matrix on Src phosphorylation and hepatocyte maturation. The inhibition of Src phosphorylation using the inhibitor PP2 or silencing the expression of Src in hASC-HLCs also attenuated the up-regulation of the metabolic function of hASC-HLCs in a nuclear receptor-dependent manner. These data elucidate integrin-Src signalling linking the extrinsic EC matrix signals and metabolic functional maturation of hepatocyte. This study provides a model for studying the interaction between hepatocytes and non-parenchymal cell-derived matrix. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  6. Structural-Acoustic Coupling Effects on the Non-Vacuum Packaging Vibratory Cylinder Gyroscope

    Science.gov (United States)

    Xi, Xiang; Wu, Xuezhong; Wu, Yulie; Zhang, Yongmeng; Tao, Yi; Zheng, Yu; Xiao, Dingbang

    2013-01-01

    The resonant shells of vibratory cylinder gyroscopes are commonly packaged in metallic caps. In order to lower the production cost, a portion of vibratory cylinder gyroscopes do not employ vacuum packaging. However, under non-vacuum packaging conditions there can be internal acoustic noise leading to considerable acoustic pressure which is exerted on the resonant shell. Based on the theory of the structural-acoustic coupling, the dynamical behavior of the resonant shell under acoustic pressure is presented in this paper. A finite element (FE) model is introduced to quantitatively analyze the effect of the structural-acoustic coupling. Several main factors, such as sealing cap sizes and degree of vacuum which directly affect the vibration of the resonant shell, are studied. The results indicate that the vibration amplitude and the operating frequency of the resonant shell will be changed when the effect of structural-acoustic coupling is taken into account. In addition, an experiment was set up to study the effect of structural-acoustic coupling on the sensitivity of the gyroscope. A 32.4 mV/°/s increase of the scale factor and a 6.2 Hz variation of the operating frequency were observed when the radial gap size between the resonant shell and the sealing cap was changed from 0.5 mm to 20 mm. PMID:24351631

  7. Optimization of process parameters during vibratory welding technique using Taguchi's analysis

    Directory of Open Access Journals (Sweden)

    Pravin Kumar Singh

    2016-09-01

    Full Text Available With an aim to improve the mechanical properties of a weld joint, a new concept of vibratory setup has been designed which is capable to stir the molten weld pool before it solidifies during shielded metal arc welding (SMAW operation. Mechanical vibration having resonance frequency of 300 Hz and amplitude of 0.5 mm was transferred to the molten weld pool of 6 mm thick mild steel butt-welded joints during the welding operation. The experimental work was conducted at various ranges of frequencies, welding current and welding speed. Taguchi's analysis technique has been applied to optimize the process parameters; the response values for analysis are yield strength and micro-hardness. The test results showed that with the application of the vibratory treatment the values of hardness and tensile properties increased. The auxiliary vibrations induced into the weld pool resulted in increased micro-hardness of the weld metal which indicates the orientation of the crystal and refinement of grains took place. This study shows that vibration applied into the weld pool can be successfully improved the mechanical properties of welded joints. Thus this research attempt provided an alternative welding technique for grain refinement of weldments.

  8. [Penile vibratory stimulation and electroejaculation in the treatment of ejaculatory dysfunction].

    Science.gov (United States)

    Fan, Long-chang; Liu, Ji-hong

    2005-03-01

    The fertility potential of infertile men can be enhanced to a great extent by the application of assisted reproduction techniques such as intrauterine insemination or in-vitro fertilization with or without intracytoplasmic sperm injection, but how to obtain semen from men with ejaculatory dysfunction remains a problem. The development and refinement of penile vibratory stimulation (PVS) and electroejaculation (EEJ) have significantly brightened the prospects for the treatment of ejaculatory dysfunction. Because vibratory stimulation is non-invasive and easy to perform, and needs no anaesthesia, it is preferred by most of the patients to EEJ, and recommended to be the first choice of treatment for ejaculatory dysfunction. Approximately 80% of all ejaculatory dysfunction men with an intact ejaculatory reflex arc (above T10 ) can obtain antegrade ejaculation by PVS. Any condition which affects the ejaculatory mechanism of the central and/or peripheral nervous system including surgical nerve injury may be treated successfully by EEJ. The purpose of this review is to present the current understanding of PVS and EEJ procedures and their clinical use in men with ejaculatory dysfunction.

  9. The guggulsterone derivative GG-52 inhibits NF-κB signaling in bone marrow-derived dendritic cells and attenuates colitis in IL-10 knockout mice.

    Science.gov (United States)

    Kang, Seung Joo; Kim, Jung Mogg; Koh, Seong-Joon; Kim, Su Hyun; Im, Jong Pil; Jung, Hyun Chae; Kim, Joo Sung

    2013-06-13

    We previously demonstrated that the novel guggulsterone derivative guggulsterone-52 (GG-52) inhibited the activation of nuclear factor (NF)-κB signaling in intestinal epithelial cells and had preventive and therapeutic effects on dextran sulfate sodium-induced acute colitis. This study investigates the anti-inflammatory effects of GG-52 on bone marrow-derived dendritic cells (BMDCs) and chronic colitis in IL-10(-/-) mice. BMDCs were generated from the femurs of C57BL/6 wild-type and IL-10(-/-) mice. BMDCs were stimulated with lipopolysaccharide (LPS) in the presence or absence of GG-52. The effect of GG-52 on NF-κB signaling in BMDCs was examined by real-time RT-PCR for IL-12p40 and TNF-α gene expression, western blotting for IκBα degradation, and electrophoretic mobility shift assay. For in vivo studies, wild-type or IL-10(-/-) mice were treated with or without GG-52. Colitis was quantified by the evaluation of histopathological findings. Double immunofluorescence staining for CD11c and phosphorylated IκB kinase (IKK)-α was performed to detect IKK activation in DCs in colonic tissue. GG-52 significantly inhibited LPS-induced IL-12p40 and TNF-α gene expression, IκBα degradation, and NF-κB DNA binding activity in BMDCs. In the IL-10(-/-) mouse model chronic colitis, administration of GG-52 significantly reduced the severity of colitis as assessed by histopathology, and suppressed IKK activation in DCs in colonic tissue. These results indicate that the novel guggulsterone derivative GG-52 blocks NF-κB activation in BMDCs and ameliorates chronic colitis in IL-10(-/-) mice, which suggest that GG-52 is a potential therapeutic agent for inflammatory bowel diseases. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Analyzing signal attenuation in PFG anomalous diffusion via a non-Gaussian phase distribution approximation approach by fractional derivatives.

    Science.gov (United States)

    Lin, Guoxing

    2016-11-21

    Anomalous diffusion exists widely in polymer and biological systems. Pulsed-field gradient (PFG) techniques have been increasingly used to study anomalous diffusion in nuclear magnetic resonance and magnetic resonance imaging. However, the interpretation of PFG anomalous diffusion is complicated. Moreover, the exact signal attenuation expression including the finite gradient pulse width effect has not been obtained based on fractional derivatives for PFG anomalous diffusion. In this paper, a new method, a Mainardi-Luchko-Pagnini (MLP) phase distribution approximation, is proposed to describe PFG fractional diffusion. MLP phase distribution is a non-Gaussian phase distribution. From the fractional derivative model, both the probability density function (PDF) of a spin in real space and the PDF of the spin's accumulating phase shift in virtual phase space are MLP distributions. The MLP phase distribution leads to a Mittag-Leffler function based PFG signal attenuation, which differs significantly from the exponential attenuation for normal diffusion and from the stretched exponential attenuation for fractional diffusion based on the fractal derivative model. A complete signal attenuation expression Eα(-Dfbα,β(*)) including the finite gradient pulse width effect was obtained and it can handle all three types of PFG fractional diffusions. The result was also extended in a straightforward way to give a signal attenuation expression of fractional diffusion in PFG intramolecular multiple quantum coherence experiments, which has an n(β) dependence upon the order of coherence which is different from the familiar n(2) dependence in normal diffusion. The results obtained in this study are in agreement with the results from the literature. The results in this paper provide a set of new, convenient approximation formalisms to interpret complex PFG fractional diffusion experiments.

  11. Analyzing signal attenuation in PFG anomalous diffusion via a non-Gaussian phase distribution approximation approach by fractional derivatives

    Science.gov (United States)

    Lin, Guoxing

    2016-11-01

    Anomalous diffusion exists widely in polymer and biological systems. Pulsed-field gradient (PFG) techniques have been increasingly used to study anomalous diffusion in nuclear magnetic resonance and magnetic resonance imaging. However, the interpretation of PFG anomalous diffusion is complicated. Moreover, the exact signal attenuation expression including the finite gradient pulse width effect has not been obtained based on fractional derivatives for PFG anomalous diffusion. In this paper, a new method, a Mainardi-Luchko-Pagnini (MLP) phase distribution approximation, is proposed to describe PFG fractional diffusion. MLP phase distribution is a non-Gaussian phase distribution. From the fractional derivative model, both the probability density function (PDF) of a spin in real space and the PDF of the spin's accumulating phase shift in virtual phase space are MLP distributions. The MLP phase distribution leads to a Mittag-Leffler function based PFG signal attenuation, which differs significantly from the exponential attenuation for normal diffusion and from the stretched exponential attenuation for fractional diffusion based on the fractal derivative model. A complete signal attenuation expression Eα(-Dfbα,β * ) including the finite gradient pulse width effect was obtained and it can handle all three types of PFG fractional diffusions. The result was also extended in a straightforward way to give a signal attenuation expression of fractional diffusion in PFG intramolecular multiple quantum coherence experiments, which has an nβ dependence upon the order of coherence which is different from the familiar n2 dependence in normal diffusion. The results obtained in this study are in agreement with the results from the literature. The results in this paper provide a set of new, convenient approximation formalisms to interpret complex PFG fractional diffusion experiments.

  12. Neural retina identity is specified by lens-derived BMP signals.

    Science.gov (United States)

    Pandit, Tanushree; Jidigam, Vijay K; Patthey, Cedric; Gunhaga, Lena

    2015-05-15

    The eye has served as a classical model to study cell specification and tissue induction for over a century. Nevertheless, the molecular mechanisms that regulate the induction and maintenance of eye-field cells, and the specification of neural retina cells are poorly understood. Moreover, within the developing anterior forebrain, how prospective eye and telencephalic cells are differentially specified is not well defined. In the present study, we have analyzed these issues by manipulating signaling pathways in intact chick embryo and explant assays. Our results provide evidence that at blastula stages, BMP signals inhibit the acquisition of eye-field character, but from neural tube/optic vesicle stages, BMP signals from the lens are crucial for the maintenance of eye-field character, inhibition of dorsal telencephalic cell identity and specification of neural retina cells. Subsequently, our results provide evidence that a Rax2-positive eye-field state is not sufficient for the progress to a neural retina identity, but requires BMP signals. In addition, our results argue against any essential role of Wnt or FGF signals during the specification of neural retina cells, but provide evidence that Wnt signals together with BMP activity are sufficient to induce cells of retinal pigment epithelial character. We conclude that BMP activity emanating from the lens ectoderm maintains eye-field identity, inhibits telencephalic character and induces neural retina cells. Our findings link the requirement of the lens ectoderm for neural retina specification with the molecular mechanism by which cells in the forebrain become specified as neural retina by BMP activity. © 2015. Published by The Company of Biologists Ltd.

  13. Identification of irradiated fruit from the pectin-derived EPR signal

    Energy Technology Data Exchange (ETDEWEB)

    Deighton, N.; Glidewell, S.M.; Goodman, B.A.; McMillan, G.P.; Perombelon, M.C.M. [Scottish Crop Research Inst., Dundee (United Kingdom)

    1996-12-31

    An EPR method based upon the observation of an unidentified multiline spectrum has been reported for the detection of irradiated fruit (dried papaya, banana, dates). A similar long-lived EPR spectrum after irradiation of dried amorphous apple pectin (BDH, 6% methyl ester) suggesting that pectin might be the origin of the signal in the dried fruit. Compositions of pectins vary greatly according to source and also with the age of the fruit itself. Therefore, a series of pectins of citrus fruit and potato tuber origin have been investigated to examine the effects of different levels of esterification on the irradiation-induced EPR signal. (author).

  14. Novel guggulsterone derivative GG-52 inhibits NF-kappaB signaling in intestinal epithelial cells and attenuates acute murine colitis.

    Science.gov (United States)

    Kim, Jung Mogg; Kang, Hyoun Woo; Cha, Mi Yeon; Yoo, Doyoung; Kim, Nayoung; Kim, In-Kyoung; Ku, Jeounghun; Kim, Sunil; Ma, Sang-Ho; Jung, Hyun Chae; Song, In Sung; Kim, Joo Sung

    2010-07-01

    We already showed that the plant sterol guggulsterone has been reported to inhibit nuclear factor-kappaB (NF-kappaB) signaling in intestinal epithelial cells (IECs) and to attenuate dextran sulfate sodium (DSS)-induced colitis. This study investigates the anti-inflammatory effects of novel guggulsterone derivatives on IEC and preventive and therapeutic murine models of DSS-induced colitis. Novel guggulsterone derivates with high lipophilicity were designed and four derivates, including GG-46, GG-50B, GG-52, and GG-53, were synthesized. Two guggulsterone derivatives, GG-50B and GG-52, significantly inhibited the activated NF-kappaB signals and the upregulated expression of interleukin-8 (IL-8) in COLO 205 cells stimulated with tumor necrosis factor-alpha (TNF-alpha). Pretreatment with GG-50B and GG-52 attenuated the increased IkappaB kinase (IKK) and IkappaBalpha phsophorylation induced by TNF-alpha. In preventive and therapeutic models of murine colitis, administration of GG-52 significantly reduced the severity of DSS-induced colitis, as assessed by disease activity index, colon length, and histology. In contrast, GG-50B did not show a significant reduction in the colitis severity. Moreover, the efficacy on attenuating colitis by GG-52 was comparable to that by sulfasalazine or prednisolone. These results indicate that the novel guggulsterone derivative GG-52 blocks NF-kappaB activation in IEC and ameliorates DSS-induced acute murine colitis, which suggests that GG-52 is a potential therapeutic agent for the treatment of inflammatory bowel diseases.

  15. Gene Expression Profile Reveals Abnormalities of Multiple Signaling Pathways in Mesenchymal Stem Cell Derived from Patients with Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Yu Tang

    2012-01-01

    Full Text Available We aimed to compare bone-marrow-derived mesenchymal stem cells (BMMSCs between systemic lupus erythematosus (SLE and normal controls by means of cDNA microarray, immunohistochemistry, immunofluorescence, and immunoblotting. Our results showed there were a total of 1, 905 genes which were differentially expressed by BMMSCs derived from SLE patients, of which, 652 genes were upregulated and 1, 253 were downregulated. Gene ontology (GO analysis showed that the majority of these genes were related to cell cycle and protein binding. Pathway analysis exhibited that differentially regulated signal pathways involved actin cytoskeleton, focal adhesion, tight junction, and TGF-β pathway. The high protein level of BMP-5 and low expression of Id-1 indicated that there might be dysregulation in BMP/TGF-β signaling pathway. The expression of Id-1 in SLE BMMSCs was reversely correlated with serum TNF-α levels. The protein level of cyclin E decreased in the cell cycling regulation pathway. Moreover, the MAPK signaling pathway was activated in BMMSCs from SLE patients via phosphorylation of ERK1/2 and SAPK/JNK. The actin distribution pattern of BMMSCs from SLE patients was also found disordered. Our results suggested that there were distinguished differences of BMMSCs between SLE patients and normal controls.

  16. Modal Damping Ratio and Optimal Elastic Moduli of Human Body Segments for Anthropometric Vibratory Model of Standing Subjects.

    Science.gov (United States)

    Gupta, Manoj; Gupta, T C

    2017-10-01

    The present study aims to accurately estimate inertial, physical, and dynamic parameters of human body vibratory model consistent with physical structure of the human body that also replicates its dynamic response. A 13 degree-of-freedom (DOF) lumped parameter model for standing person subjected to support excitation is established. Model parameters are determined from anthropometric measurements, uniform mass density, elastic modulus of individual body segments, and modal damping ratios. Elastic moduli of ellipsoidal body segments are initially estimated by comparing stiffness of spring elements, calculated from a detailed scheme, and values available in literature for same. These values are further optimized by minimizing difference between theoretically calculated platform-to-head transmissibility ratio (TR) and experimental measurements. Modal damping ratios are estimated from experimental transmissibility response using two dominant peaks in the frequency range of 0-25 Hz. From comparison between dynamic response determined form modal analysis and experimental results, a set of elastic moduli for different segments of human body and a novel scheme to determine modal damping ratios from TR plots, are established. Acceptable match between transmissibility values calculated from the vibratory model and experimental measurements for 50th percentile U.S. male, except at very low frequencies, establishes the human body model developed. Also, reasonable agreement obtained between theoretical response curve and experimental response envelop for average Indian male, affirms the technique used for constructing vibratory model of a standing person. Present work attempts to develop effective technique for constructing subject specific damped vibratory model based on its physical measurements.

  17. Sonic hedgehog (SHH) signaling improves the angiogenic potential of Wharton's jelly-derived mesenchymal stem cells (WJ-MSC).

    Science.gov (United States)

    Zavala, Gabriela; Prieto, Catalina P; Villanueva, Andrea A; Palma, Verónica

    2017-09-29

    Wharton's jelly-derived mesenchymal stem cells (WJ-MSC) show remarkable therapeutic potential to repair tissue upon injury via paracrine signaling by secreting diverse trophic factors that promote angiogenesis. However, the mechanisms and signaling pathways that regulate the induction of these specific factors are still mostly unknown. Emerging evidence suggests that Sonic hedgehog (SHH) plays a central role in angiogenesis and tissue maintenance. However, its contribution to the angiogenic potential of MSC has not been fully addressed. The aim of this work was to characterize the expression of the SHH pathway components in WJ-MSC primary cultures and to evaluate their angiogenic responsiveness to SHH signaling. Primary cell cultures obtained from human umbilical cords were treated with pharmacological modulators of the SHH pathway. We evaluated the modulation of diverse trophic factors in cell lysates, conditioned medium, and functional in vitro assays. In addition, we determined the angiogenic potential of the SHH pathway in the chicken chorioallantoic membrane, an in vivo model. Our results show that WJ-MSC express components of the canonical SHH pathway and are activated by its signaling. In fact, we provide evidence of basal autocrine/paracrine SHH signaling in WJ-MSC. SHH pathway stimulation promotes the secretion of angiogenic factors such as activin A, angiogenin, angiopoietin 1, granulocyte-macrophage colony-stimulating factor, matrix metallometallopeptidase -9, and urokinase-type plasminogen activator, enhancing the pro-angiogenic capabilities of WJ-MSC both in vitro and in vivo. WJ-MSC are a cell population responsive to SHH pathway stimulation. Basal SHH signaling is in part responsible for the angiogenic inductive properties of WJ-MSC. Overall, exogenous activation of the SHH pathway enhances the angiogenic properties of WJ-MSC, making this cell population an ideal target for treating tissue injury.

  18. Critical role of SHP2 (PTPN11) signaling in germinal center-derived lymphoma.

    Science.gov (United States)

    Jiang, Xin; Guo, Honggang; Wu, Jianguo; He, Qiang; Li, Yiqiao; Wang, Miao; Pan, Hongyang; Li, Wande; Wang, Jinjie; Wang, Qingqing; Shen, Jing; Ke, Yuehai; Zhou, Ren

    2014-12-01

    Germinal center lymphoma is a heterogeneous human lymphoma entity. Here we report that constitutive activity of SHP2 (PTPN11) and its downstream kinase ERK is essential for the viability of germinal center lymphoma cells and disease progression. Mechanistically, SHP2/ERK inhibition impedes c-Myc transcriptional activity, which results in the repression of proliferative phenotype signatures of germinal center lymphoma. Furthermore, SHP2/ERK signaling is required to maintain the CD19/c-Myc loop, which preferentially promotes survival of a distinct subtype of germinal center lymphoma cells carrying the MYC/IGH translocation. These findings demonstrate a critical function for SHP2/ERK signaling upstream of c-Myc in germinal center lymphoma cells and provide a rationale for targeting SHP2 in the therapy of germinal center lymphoma. Copyright© Ferrata Storti Foundation.

  19. Gold Superparticles Functionalized with Azobenzene Derivatives: SERS Nanotags with Strong Signals.

    Science.gov (United States)

    Ma, Ying; Promthaveepong, Kittithat; Li, Nan

    2017-03-29

    The surface-enhanced Raman spectroscopy (SERS) nanotag was proposed as a substitute for fluorescent dye for imaging and biosensors several decades ago. However, its weak signal and poor reproducibility has hindered its application. Here, we report a new strategy to form Au superparticles (AuSPs) with high SERS enhancement via one-pot formation and self-assembly of Au nanoparticles (NPs). An azobenzene-carrying Raman reporter was synthesized to exhibit a large Raman cross-section and multiple bands. The self-assembly of the Raman reporter on AuSPs generated SERS nanotags with intense signals. A Raman reporter carrying boronic acid and azobenzene groups displayed six distinctive bands. Its corresponding SERS nanotag demonstrated a high sensing ability toward glycoprotein through aggregation-induced SERS enhancement or as a substitute for labeled antibodies in an immunoassay of the glycoprotein.

  20. The differential activation of intracellular signaling pathways confers the permissiveness of embryonic stem cell derivation from different mouse strains

    Science.gov (United States)

    Ohtsuka, Satoshi; Niwa, Hitoshi

    2015-01-01

    The requirement of leukemia inhibitory factor (LIF) for the establishment and maintenance of mouse embryonic stem cells (ESCs) depends on the genetic background of the ESC origin. To reveal the molecular basis of the strain-dependent function of LIF, we compared the activation of the intracellular signaling pathways downstream of LIF in ESCs with different genetic backgrounds. We found that the JAK-Stat3 pathway was dominantly activated in ESCs derived from ‘permissive’ mouse strains (129Sv and C57BL6), whereas the MAP kinase pathway was hyperactivated in ESCs from ‘non-permissive’ strains (NOD, CBA and FVB). Artificial activation of Stat3 supported stable self-renewal of ESCs from non-permissive strains. These data suggest that the difference in the balance between the two intracellular signaling pathways underlies the differential response to LIF. PMID:25564647

  1. Whole-Genome Expression Analysis and Signal Pathway Screening of Synovium-Derived Mesenchymal Stromal Cells in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Jingyi Hou

    2016-01-01

    Full Text Available Synovium-derived mesenchymal stromal cells (SMSCs may play an important role in the pathogenesis of rheumatoid arthritis (RA and show promise for therapeutic applications in RA. In this study, a whole-genome microarray analysis was used to detect differential gene expression in SMSCs from RA patients and healthy donors (HDs. Our results showed that there were 4828 differentially expressed genes in the RA group compared to the HD group; 3117 genes were upregulated, and 1711 genes were downregulated. A Gene Ontology analysis showed significantly enriched terms of differentially expressed genes in the biological process, cellular component, and molecular function domains. A Kyoto Encyclopedia of Genes and Genomes analysis showed that the MAPK signaling and rheumatoid arthritis pathways were upregulated and that the p53 signaling pathway was downregulated in RA SMSCs. Quantitative real-time polymerase chain reaction was applied to verify the expression variations of the partial genes mentioned above, and a western blot analysis was used to determine the expression levels of p53, p-JNK, p-ERK, and p-p38. Our study found that differentially expressed genes in the MAPK signaling, rheumatoid arthritis, and p53 signaling pathways may help to explain the pathogenic mechanism of RA and lead to therapeutic RA SMSC applications.

  2. Dendritic cell derived IL-2 inhibits survival of terminally mature cells via an autocrine signaling pathway.

    Science.gov (United States)

    Balachander, Akhila; Nabti, Sabrina; Sobota, Radoslaw M; Foo, Shihui; Zolezzi, Francesca; Lee, Bernett T K; Poidinger, Michael; Ricciardi-Castagnoli, Paola

    2015-05-01

    DCs are crucial for sensing pathogens and triggering immune response. Upon activation by pathogen-associated molecular pattern (PAMP) ligands, GM-CSF myeloid DCs (GM-DCs) secrete several cytokines, including IL-2. DC IL-2 has been shown to be important for innate and adaptive immune responses; however, IL-2 importance in DC physiology has never been demonstrated. Here, we show that autocrine IL-2 signaling is functional in murine GM-DCs in an early time window after PAMPs stimulation. IL-2 signaling selectively activates the JAK/STAT5 pathway by assembling holo-receptor complexes at the cell surface. Using the sensitivity of targeted mass spectrometry, we show conclusively that GM-DCs express CD122, the IL-2 receptor β-chain, at steady state. In myeloid DCs, this cytokine pathway inhibits survival of PAMP-matured GM-DCs which is crucial for maintaining immune tolerance and preventing autoimmunity. Our findings suggest that immune regulation by this novel autocrine signaling pathway can potentially be used in DC immunotherapy. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Human tumor-derived exosomes (TEX) regulate Treg functions via cell surface signaling rather than uptake mechanisms.

    Science.gov (United States)

    Muller, Laurent; Simms, Patricia; Hong, Chang-Sook; Nishimura, Michael I; Jackson, Edwin K; Watkins, Simon C; Whiteside, Theresa L

    2017-01-01

    Tumor-derived exosomes (TEX) are ubiquitously present in the tumor microenvironment and plasma of cancer patients. TEX carry a cargo of multiple stimulatory and inhibitory molecules and deliver them to recipient cells, serving as a communication network for the tumor. The mechanisms TEX use for delivering messages to recipient cells were evaluated using PKH26-labeled TEX produced by cultured human tumor cells, exosomes produced by dendritic cells-derived exosomes (DEX), or exosomes isolated from plasma of cancer patients (EXO). Human T-cell subsets, B cells, NK cells, and monocytes were co-incubated with TEX, DEX, or EXO and binding or internalization of labeled vesicles was evaluated by confocal microscopy and/or Amnis-based flow cytometry. Vesicle-induced Ca2+ influx in recipient T cells was monitored, and TEX-induced inosine production in Treg was determined by mass spectrometry. In contrast to B cells, NK cells or monocytes, conventional T cells did not internalize labeled vesicles. Minimal exosome uptake was only evident in Treg following prolonged co-incubation with TEX. All exosomes induced Ca2+ influx in T cells, with TEX and EXO isolated from cancer patients' plasma delivering the strongest, sustained signaling to Treg. Such sustained signaling resulted in the significant upregulation of the conversion of extracellular ATP to inosine (adenosine metabolite) by Treg, suggesting that TEX signaling could have functional consequences in these recipient cells. Thus, modulation of Treg suppressor functions by TEX is mediated by mechanisms dependent on cell surface signaling and does not require TEX internalization by recipient cells.

  4. Pigment Epithelium-Derived Factor (PEDF Inhibits Wnt/β-catenin Signaling in the LiverSummary

    Directory of Open Access Journals (Sweden)

    Petr Protiva

    2015-09-01

    Full Text Available Background & Aims: Pigment epithelium-derived factor (PEDF is a secretory protein that inhibits multiple tumor types. PEDF inhibits the Wnt coreceptor, low-density lipoprotein receptor-related protein 6 (LRP6, in the eye, but whether the tumor-suppressive properties of PEDF occur in organs such as the liver is unknown. Methods: Wnt-dependent regulation of PEDF was assessed in the absence and presence of the Wnt coreceptor LRP6. Whole genome expression analysis was performed on PEDF knockout (KO and control livers (7 months. Interrogation of Wnt/β-catenin signaling was performed in whole livers and human hepatocellular carcinoma (HCC cell lines after RNA interference of PEDF and restoration of a PEDF-derived peptide. Western diet feeding for 6 to 8 months was used to evaluate whether the absence of PEDF was permissive for HCC formation (n = 12/group. Results: PEDF levels increased in response to canonical Wnt3a in an LRP6-dependent manner but were suppressed by noncanonical Wnt5a protein in an LRP6-independent manner. Gene set enrichment analysis (GSEA of PEDF KO livers revealed induction of pathways associated with experimental and human HCC and a transcriptional profile characterized by Wnt/β-catenin activation. Enhanced Wnt/β-catenin signaling occurred in KO livers, and PEDF delivery in vivo reduced LRP6 activation. In human HCC cells, RNA interference of PEDF led to increased levels of activated LRP6 and β-catenin, and a PEDF 34-mer peptide decreased LRP6 activation and β-catenin signaling, and reduced Wnt target genes. PEDF KO mice fed a Western diet developed sporadic well-differentiated HCC. Human HCC specimens demonstrated decreased PEDF staining compared with hepatocytes. Conclusions: PEDF is an endogenous inhibitor of Wnt/β-catenin signaling in the liver. Keywords: Extracellular Matrix, PEDF, Wnt/β-Catenin

  5. The effect of signal leakage and glacial isostatic rebound on GRACE-derived ice mass changes in Iceland

    DEFF Research Database (Denmark)

    Sørensen, Louise Sandberg; Jarosch, Alexander H.; Adalgeirsdottir, Gudfinna

    2017-01-01

    Monthly gravity field models from the GRACE satellite mission are widely used to determine ice mass changes of large ice sheets as well as smaller glaciers and ice caps. Here, we investigate in detail the ice mass changes of the Icelandic ice caps as derived from GRACE data. The small size...... of the Icelandic ice caps, their location close to other rapidly changing ice covered areas and the low viscosity of the mantle below Iceland make this especially challenging. The mass balance of the ice caps is well constrained by field mass balance measurements, making this area ideal for such investigations. We...... find that the ice mass changes of the Icelandic ice caps derived from GRACE gravity field models are influenced by both the large gravity change signal resulting from ice mass loss in southeast Greenland and the mass redistribution within the Earth mantle due to glacial isostatic adjustment since...

  6. Osteoclasts secrete non-bone derived signals that induce bone formation

    DEFF Research Database (Denmark)

    Karsdal, Morten A; Neutzsky-Wulff, Anita V; Dziegiel, Morten Hanefeld

    2008-01-01

    Bone turnover is a highly regulated process, where bone resorption in the normal healthy individual always is followed by bone formation in a manner referred to as coupling. Patients with osteopetrosis caused by defective acidification of the resorption lacuna have severely decreased resorption, ...... secrete non-bone derived factors, which induce preosteoblasts to form bone-like nodules, potentially explaining the imbalanced coupling seen in osteopetrotic patients....

  7. Effect of residual stress on modal patterns of MEMS vibratory gyroscope

    Energy Technology Data Exchange (ETDEWEB)

    Dutta, Shankar, E-mail: shankardutta77@gmail.com; Panchal, Abha; Kumar, Manoj; Pal, Ramjay; Bhan, R. K. [Solid State Physics Laboratory, DRDO, Lucknow Road, Timarpur, Delhi, India 110054 (India)

    2016-04-13

    Deep boron diffusion often induces residual stress in bulk micromachined MEMS structures, which may affect the MEMS devices operation. In this study, we studied the modal patterns of MEMS vibratory gyroscope under the residual stress (100 – 1000 MPa). Modal patterns and modal frequencies of the gyro are found to be dependent on the residual stress values. Without any residual stress, the modal frequencies drive and sense modeswere found to be 20.06 kHz and 20.36 kHz respectively. In presence of 450 MPa residual stress, the modal frequencies of the drive and sense modes were changed to 42.75 kHz and 43.07 kHz respectively.

  8. Characterization of vibratory turning in cutting zone using a pneumatic quick-stop device

    Directory of Open Access Journals (Sweden)

    Saeid Amini

    2017-04-01

    Full Text Available Shear angle and sticking length are two crucial parameters in mechanics of metal cutting. These two parameters directly influence machinability factors such as cutting forces. Thus, shear angle and sticking length were investigated in vibratory turning process by using a pneumatic quick-stop device which was designed and fabricated, in this study. After preparation of ultrasonic assisted turning set-up, experimental tests have been carried out on two types of steel: AISI-1060 and AISI 304. Accordingly, the process of chip formation in each particular cutting test was quickly stopped when deformed chip was still in contact with workpiece. As a result, it was revealed that added linear vibration leads the turning operation to be improved by increase of shear angle and decrease of sticking length. Moreover, the effect of ultrasonic vibration on cutting force and chip micro-hardness is evaluated.

  9. Interspectral combination type resonances of nonlinear conservative/nonconservative distributed parameter vibratory systems

    Science.gov (United States)

    Padovan, J.

    1985-06-01

    This paper investigates the properties/formation of combination type resonances of nonlinear conservative/nonconservative distributed parameter vibratory systems subject to external harmonic inputs containing a profusion of frequencies. Overall, this includes the evaluation of simultaneously excited harmonic, sub/superharmonics as well as combination harmonics created by interactions between external and interspectral system frequency branches. Additionally, effort is also given to handling nonconservative characteristics wherein critical damping levels may suppress specific combination harmonics. The foregoing is made possible through the development of a warped and constrained multiple time scales perturbation solution scheme. To illustrate the scheme as well as the nature and form of external and interspectral interaction, a nonlinear nonconservative version of the wave equation which is excited by complex external harmonic fields is given detailed consideration.

  10. Development of vibratory stress relief actuators based on giant magnetostrictive materials

    Science.gov (United States)

    He, Wen

    2005-12-01

    A kind of actuator, which is used in the high frequency Vibratory Stress Relief (VSR), was researched. The actuator is based on the technology of giant magnetostrictive materials. The design principle of the actuator was firstly analyzed, which consists of the analysis of giant magnetostrictive materials and a force generator. Then the design criterion of magnetostrictive actuators was deeply discussed, which includes the dimension design of magnetostrictive materials, the design of magnetic field and the design of elimination of heat. Finally, a real actuator was developed, which has been used in the high frequency VSR. The experimental results show that the developed actuator works very well. Large exciting force but small vibration amplitude will make it widely used in the VSR.

  11. Application of vibratory-percussion crusher for disintegration of supertough materials

    Science.gov (United States)

    Shishkin, E. V.; Kazakov, S. V.

    2017-10-01

    This article describes the results of theoretical and experimental studies of a vibratory-percussion crusher, which is driven from a pair of self-synchronizing vibration exciters, attached to the shell symmetrically about its vertical axis. In addition to that, crusher’s dynamic model is symmetrical and balanced. Forced oscillation laws for crusher working members and their amplitude-frequency characteristics have been inducted. Domains of existence of synchronous opposite-phase oscillations of crusher working members (crusher’s operating mode) and crusher capabilities have been identified. The results of mechanical and technological tests of a pilot crusher presented in the article show that this crusher may be viewed as an advanced machine for disintegration of supertough materials with minimum regrinding of finished products.

  12. Vibratory synchronization transmission of a cylindrical roller in a vibrating mechanical system excited by two exciters

    Science.gov (United States)

    Zhang, Xueliang; Wen, Bangchun; Zhao, Chunyu

    2017-11-01

    In present work vibratory synchronization transmission (VST) of a cylindrical roller with dry friction in a vibrating mechanical system excited by two exciters, is studied. Using the average method, the criterion of implementing synchronization of two exciters and that of ensuring VST of a roller, are achieved. The criterion of stability of the synchronous states satisfies the Routh-Hurwitz principle. The influences of the structural parameters of the system to synchronization and stability, are discussed numerically, which can be served as the theoretical foundation for engineering designs. An experiment is carried out, which approximately verify the validity of the theoretical and numerical results, as well as the feasibility of the method used. Utilizing the VST theory of a roller, some types of vibrating crushing or grinding equipments, etc., can be designed.

  13. Escherichia coli-derived and Staphylococcus aureus-derived extracellular vesicles induce MUC5AC expression via extracellular signal related kinase 1/2 and p38 mitogen-activated protein kinase in human airway epithelial cells.

    Science.gov (United States)

    Bae, Chang Hoon; Choi, Yoon Seok; Song, Si-Youn; Kim, Yoon-Keun; Kim, Yong-Dae

    2017-01-01

    Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) release extracellular vesicles (EVs). E. coli-derived and S. aureus-derived EVs are associated with neutrophilic respiratory inflammation. In neutrophilic respiratory inflammation of human, expression of mucin is increased in airway epithelial cells and is associated with increased morbidity and mortality of the affected patients. However, no study on the effects of EVs on expression of mucin genes has been reported in airway epithelial cells. Therefore, this study was conducted in order to examine the effects and the brief signaling pathways of E. coli-derived and S. aureus-derived EVs on MUC5AC expression in human airway epithelial cells. In mucin-producing human NCI-H292 airway epithelial cells and primary cultures of normal nasal epithelial cells, the effects and signaling pathways of E. coli-derived and S. aureus-derived EVs on MUC5AC expression were examined using reverse transcription-polymerase chain reaction (RT-PCR), real-time PCR, enzyme immunoassay, and immunoblot analysis with several specific inhibitors and small interfering RNA (siRNA). E. coli-derived and S. aureus-derived EVs induced MUC5AC expression. E. coli-derived and S. aureus-derived EVs significantly activated phosphorylation of extracellular signal related kinase 1/2 (ERK1/2) mitogen-activated protein kinase (MAPK) and p38 MAPK. ERK1/2 MAPK inhibitor, p38 MAPK inhibitor, ERK1/2 MAPK siRNA, and p38 MAPK siRNA significantly blocked E. coli-derived and S. aureus-derived EVs induced MUC5AC messenger RNA (mRNA) expression. The results of this study suggest that E. coli-derived and S. aureus-derived EVs induced MUC5AC expression via ERK1/2 and p38 MAPK signaling pathways in human airway epithelial cells. © 2016 ARS-AAOA, LLC.

  14. Maternal obesity alters brain derived neurotrophic factor (BDNF) signaling in the placenta in a sexually dimorphic manner.

    Science.gov (United States)

    Prince, Calais S; Maloyan, Alina; Myatt, Leslie

    2017-01-01

    Obesity is a major clinical problem in obstetrics being associated with adverse pregnancy outcomes and fetal programming. Brain derived neurotrophic factor (BDNF), a validated miR-210 target, is necessary for placental development, fetal growth, glucose metabolism, and energy homeostasis. Plasma BDNF levels are reduced in obese individuals; however, placental BDNF has yet to be studied in the context of maternal obesity. In this study, we investigated the effect of maternal obesity and sexual dimorphism on placental BDNF signaling. BDNF signaling was measured in placentas from lean (pre-pregnancy BMI 30) women at term without medical complications that delivered via cesarean section without labor. MiRNA-210, BDNF mRNA, proBDNF, and mature BDNF were measured by RT - PCR, ELISA, and Western blot. Downstream signaling via TRKB (BDNF receptor) was measured using Western blot. Maternal obesity was associated with increased miRNA-210 and decreased BDNF mRNA in placentas from female fetuses, and decreased proBDNF in placentas from male fetuses. We also identified decreased mature BDNF in placentas from male fetuses when compared to female fetuses. Mir-210 expression was negatively correlated with mature BDNF protein. TRKB phosphorylated at tyrosine 817, not tyrosine 515, was increased in placentas from obese women. Maternal obesity was associated with increased phosphorylation of MAPK p38 in placentas from male fetuses, but not phosphorylation of ERK p42/44. BDNF regulation is complex and highly regulated. Pre-pregnancy/early maternal obesity adversely affects BDNF/TRKB signaling in the placenta in a sexually dimorphic manner. These data collectively suggest that induction of placental TRKB signaling could ameliorate the placental OB phenotype, thus improving perinatal outcome. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. The quassinoid derivative NBT-272 targets both the AKT and ERK signaling pathways in embryonal tumors.

    Science.gov (United States)

    Castelletti, Deborah; Fiaschetti, Giulio; Di Dato, Valeria; Ziegler, Urs; Kumps, Candy; De Preter, Katleen; Zollo, Massimo; Speleman, Frank; Shalaby, Tarek; De Martino, Daniela; Berg, Thorsten; Eggert, Angelika; Arcaro, Alexandre; Grotzer, Michael A

    2010-12-01

    The quassinoid analogue NBT-272 has been reported to inhibit MYC, thus warranting a further effort 7to better understand its preclinical properties in models of embryonal tumors (ET), a family of childhood malignancies sharing relevant biological and genetic features such as deregulated expression of MYC oncogenes. In our study, NBT-272 displayed a strong antiproliferative activity in vitro that resulted from the combination of diverse biological effects, ranging from G(1)/S arrest of the cell cycle to apoptosis and autophagy. The compound prevented the full activation of both eukaryotic translation initiation factor 4E (eIF4E) and its binding protein 4EBP-1, regulating cap-dependent protein translation. Interestingly, all responses induced by NBT-272 in ET could be attributed to interference with 2 main proproliferative signaling pathways, that is, the AKT and the MEK/extracellular signal-regulated kinase pathways. These findings also suggested that the depleting effect of NBT-272 on MYC protein expression occurred via indirect mechanisms, rather than selective inhibition. Finally, the ability of NBT-272 to arrest tumor growth in a xenograft model of neuroblastoma plays a role in the strong antitumor activity of this compound, both in vitro and in vivo, with its potential to target cell-survival pathways that are relevant for the development and progression of ET.

  16. Behavioral Signal Processing: Deriving Human Behavioral Informatics From Speech and Language

    Science.gov (United States)

    Narayanan, Shrikanth; Georgiou, Panayiotis G.

    2013-01-01

    The expression and experience of human behavior are complex and multimodal and characterized by individual and contextual heterogeneity and variability. Speech and spoken language communication cues offer an important means for measuring and modeling human behavior. Observational research and practice across a variety of domains from commerce to healthcare rely on speech- and language-based informatics for crucial assessment and diagnostic information and for planning and tracking response to an intervention. In this paper, we describe some of the opportunities as well as emerging methodologies and applications of human behavioral signal processing (BSP) technology and algorithms for quantitatively understanding and modeling typical, atypical, and distressed human behavior with a specific focus on speech- and language-based communicative, affective, and social behavior. We describe the three important BSP components of acquiring behavioral data in an ecologically valid manner across laboratory to real-world settings, extracting and analyzing behavioral cues from measured data, and developing models offering predictive and decision-making support. We highlight both the foundational speech and language processing building blocks as well as the novel processing and modeling opportunities. Using examples drawn from specific real-world applications ranging from literacy assessment and autism diagnostics to psychotherapy for addiction and marital well being, we illustrate behavioral informatics applications of these signal processing techniques that contribute to quantifying higher level, often subjectively described, human behavior in a domain-sensitive fashion. PMID:24039277

  17. Three-dimensional culture and cAMP signaling promote the maturation of human pluripotent stem cell-derived hepatocytes

    Science.gov (United States)

    Ogawa, Shinichiro; Surapisitchat, James; Virtanen, Carl; Ogawa, Mina; Niapour, Maryam; Sugamori, Kim S.; Wang, Shuang; Tamblyn, Laura; Guillemette, Chantal; Hoffmann, Ewa; Zhao, Bin; Strom, Stephen; Laposa, Rebecca R.; Tyndale, Rachel F.; Grant, Denis M.; Keller, Gordon

    2013-01-01

    Human pluripotent stem cells (hPSCs) represent a novel source of hepatocytes for drug metabolism studies and cell-based therapy for the treatment of liver diseases. These applications are, however, dependent on the ability to generate mature metabolically functional cells from the hPSCs. Reproducible and efficient generation of such cells has been challenging to date, owing to the fact that the regulatory pathways that control hepatocyte maturation are poorly understood. Here, we show that the combination of three-dimensional cell aggregation and cAMP signaling enhance the maturation of hPSC-derived hepatoblasts to a hepatocyte-like population that displays expression profiles and metabolic enzyme levels comparable to those of primary human hepatocytes. Importantly, we also demonstrate that generation of the hepatoblast population capable of responding to cAMP is dependent on appropriate activin/nodal signaling in the definitive endoderm at early stages of differentiation. Together, these findings provide new insights into the pathways that regulate maturation of hPSC-derived hepatocytes and in doing so provide a simple and reproducible approach for generating metabolically functional cell populations. PMID:23861064

  18. Xyloglucan octasaccharide XXLGol derived from the seeds of hymenaea courbaril acts as a signaling molecule

    Science.gov (United States)

    Vargas-Rechia; Reicher; Rita Sierakowski M; Heyraud; Driguez; Linart

    1998-03-01

    Treatment of the xyloglucan isolated from the seeds of Hymenaea courbaril with Humicola insolens endo-1,4-beta-d-glucanase I produced xyloglucan oligosaccharides, which were then isolated and characterized. The two most abundant compounds were the heptasaccharide (XXXG) and the octasaccharide (XXLG), which were examined by reference to the biological activity of other structurally related xyloglucan compounds. The reduced oligomer (XXLGol) was shown to promote growth of wheat (Triticum aestivum) coleoptiles independently of the presence of 2, 4-dichlorophenoxyacetic acid (2,4-D). In the presence of 2,4-D, XXLGol at nanomolar concentrations increased the auxin-induced response. It was found that XXLGol is a signaling molecule, since it has the ability to induce, at nanomolar concentrations, a rapid increase in an alpha-l-fucosidase response in suspended cells or protoplasts of Rubus fruticosus L. and to modulate 2,4-D or gibberellic acid-induced alpha-l-fucosidase.

  19. Xyloglucan Octasaccharide XXLGol Derived from the Seeds of Hymenaea courbaril Acts as a Signaling Molecule1

    Science.gov (United States)

    Vargas-Rechia, Carem; Reicher, Fany; Rita Sierakowski, Maria; Heyraud, Alain; Driguez, Hugues; Liénart, Yvette

    1998-01-01

    Treatment of the xyloglucan isolated from the seeds of Hymenaea courbaril with Humicola insolens endo-1,4-β-d-glucanase I produced xyloglucan oligosaccharides, which were then isolated and characterized. The two most abundant compounds were the heptasaccharide (XXXG) and the octasaccharide (XXLG), which were examined by reference to the biological activity of other structurally related xyloglucan compounds. The reduced oligomer (XXLGol) was shown to promote growth of wheat (Triticum aestivum) coleoptiles independently of the presence of 2,4-dichlorophenoxyacetic acid (2,4-D). In the presence of 2,4-D, XXLGol at nanomolar concentrations increased the auxin-induced response. It was found that XXLGol is a signaling molecule, since it has the ability to induce, at nanomolar concentrations, a rapid increase in an α-l-fucosidase response in suspended cells or protoplasts of Rubus fruticosus L. and to modulate 2,4-D or gibberellic acid-induced α-l-fucosidase. PMID:9501133

  20. Cabergoline, a dopamine receptor agonist, has an antidepressant-like property and enhances brain-derived neurotrophic factor signaling.

    Science.gov (United States)

    Chiba, Shuichi; Numakawa, Tadahiro; Ninomiya, Midori; Yoon, Hyung Shin; Kunugi, Hiroshi

    2010-08-01

    Dopamine agonists have been implicated in the treatment of depression. Cabergoline is an ergot derivative with a high affinity to dopamine D(2)-like receptors; however, there have been few preclinical studies on its antidepressant-like effects. Behavioral effects of cabergoline were examined in rats using forced swimming (FST), novelty-suppressed feeding (NST), open field (OFT), and elevated-plus maze (EPT) tests. In a single treatment paradigm, behaviors of rats were analyzed 4 h after single injection of cabergoline (s.c., 0-4 micromol/kg). In a repeated-treatment paradigm, OFT, EPT, and FST were conducted on days 11, 12, and 13-14, respectively, during daily cabergoline injections (s.c., 0.5 micromol/kg), and then hippocampus was removed 24 h after the last injection. NST was conducted in a separate experiment at day 14. Western blotting was used for the analysis of the protein levels of brain-derived neurotrophic factor (BDNF) and the activation of intracellular signaling molecules. Single injection of cabergoline demonstrated decreased immobility in FST and distance traveled during 0-10 min in OFT, while time spent and entry into open arms were increased at 4 micromol/kg. When cabergoline was repeatedly administered, immobility in FST and the latency of feeding in NSF were significantly reduced, while vertical movement was increased in OFT. The time in closed arms was tended to be decreased in EPT. Expression of BDNF and activation of extracellular signal-regulated kinase 1 were up-regulated after the chronic administration of cabergoline. Cabergoline exerts antidepressant- and anxiolytic-like effects, which may be mediated by potentiation of intracellular signaling of BDNF.

  1. Neuroprotective effect of a novel gastrodin derivative against ischemic brain injury: involvement of peroxiredoxin and TLR4 signaling inhibition

    Science.gov (United States)

    Mao, Xiao-Na; Zhou, Hong-Jing; Yang, Xiao-Jia; Zhao, Li-Xue; Kuang, Xi; Chen, Chu; Liu, Dong-Ling; Du, Jun-Rong

    2017-01-01

    The inhibition of extracellular inflammatory peroxiredoxin (Prx) signaling appears to be a potential therapeutic strategy for neuroinflammatory injury after acute ischemic stroke. Gastrodin (Gas) is a phenolic glycoside that is used for the treatment of cerebral ischemia, accompanied by regulation of the autoimmune inflammatory response. The present study investigated the neuroprotective effects of Gas and its derivative, Gas-D, with a focus on the potential mechanism associated with inflammatory Prx–Toll-like receptor 4 (TLR4) signaling. Gas-D significantly inhibited Prx1-, Prx2-, and Prx4-induced inflammatory responses in RAW264.7 macrophages and H2O2-mediated oxidative injury in SH-SY5Y nerve cells. In rats, intraperitoneal Gas-D administration 10 h after reperfusion following 2-h middle cerebral artery occlusion (MCAO) ameliorated neurological deficits, brain infarction, and neuropathological alterations, including neuron loss, astrocyte and microglia/macrophage activation, T-lymphocyte invasion, and lipid peroxidation. Delayed Gas-D treatment significantly inhibited postischemic Prx1/2/4 expression and spillage, TLR4 signaling activation, and inflammatory mediator production. In contrast, Gas had no significant effects in either cell model or in MCAO rats under the same conditions. These results indicate that Gas-D may be a drug candidate with an extended therapeutic time window that blocks inflammatory responses and attenuates the expression and secretome of inflammatory Prxs in acute ischemic stroke. PMID:29207618

  2. Effect of Wnt Signaling on the Differentiation of Islet β-Cells from Adipose-Derived Stem Cells

    Directory of Open Access Journals (Sweden)

    Hefei Wang

    2017-01-01

    Full Text Available The Wnt signaling is critical for pancreatic development and islet function; however, its precise effects on the development and function of the β-cells remain controversial. Here we examined mRNA and protein expression of components of the Wnt signaling throughout the differentiation of islet β-cells from adipose-derived stem cells (ADSCs. After induction, ADSCs expressed markers of β-cells, including the insulin, PDX1, and glucagon genes, and the PDX1, CK19, nestin, insulin, and C-peptide proteins, indicating their successful differentiation. Compared with pancreatic adult stem cells (PASCs, the quantities of insulin, GLUT2, and Irs2 mRNA decreased, whereas Gcg, Gck, and Irs1 mRNA increased. Over time, during differentiation, insulin mRNA and protein expression increased, Gcg and Gck mRNA expression increased, Irs1 mRNA expression decreased and then increased, and Irs2 mRNA increased and then decreased (all P0.05. Our results indicate that the Wnt signaling is activated during ADSC differentiation into islet β-cells, but there was no obvious enrichment of nonphosphorylated β-catenin protein.

  3. Brain-derived neurotrophic factor signalling mediates the antidepressant-like effect of piperine in chronically stressed mice.

    Science.gov (United States)

    Mao, Qing-Qiu; Huang, Zhen; Zhong, Xiao-Ming; Xian, Yan-Fang; Ip, Siu-Po

    2014-03-15

    Previous studies in our laboratory have demonstrated that piperine produced antidepressant-like action in various mouse models of behavioral despair. This study aimed to investigate the role of brain-derived neurotrophic factor (BDNF) signalling in the antidepressant-like effect of piperine in mice exposed to chronic unpredictable mild stress (CUMS). The results showed that CUMS caused depression-like behavior in mice, as indicated by the significant decrease in sucrose consumption and increase in immobility time in the forced swim test. It was also found that BDNF protein expression in the hippocampus and frontal cortex were significantly decreased in CUMS-treated mice. Chronic treatment of piperine at the dose of 10mg/kg significantly ameliorated behavioural deficits of CUMS-treated mice in the sucrose preference test and forced swim test. Piperine treatment also significantly decreased immobility time in the forced swim test in naive mice. In parallel, chronic piperine treatment significantly increased BDNF protein expression in the hippocampus and frontal cortex of both naive and CUMS-treated mice. In addition, inhibition of BDNF signalling by injection of K252a, an inhibitor of the BDNF receptor TrkB, significantly blocked the antidepressant-like effect of piperine in the sucrose preference test and forced swim test of CUMS-treated mice. Taken together, this study suggests that BDNF signalling is an essential mediator for the antidepressant-like effect of piperine. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Analytical Derivation of Nonlinear Spectral Effects and 1/f Scaling Artifact in Signal Processing of Real-World Data.

    Science.gov (United States)

    Lainscsek, Claudia; Muller, Lyle E; Sampson, Aaron L; Sejnowski, Terrence J

    2017-07-01

    In estimating the frequency spectrum of real-world time series data, we must violate the assumption of infinite-length, orthogonal components in the Fourier basis. While it is widely known that care must be taken with discretely sampled data to avoid aliasing of high frequencies, less attention is given to the influence of low frequencies with period below the sampling time window. Here, we derive an analytic expression for the side-lobe attenuation of signal components in the frequency domain representation. This expression allows us to detail the influence of individual frequency components throughout the spectrum. The first consequence is that the presence of low-frequency components introduces a 1/f[Formula: see text] component across the power spectrum, with a scaling exponent of [Formula: see text]. This scaling artifact could be composed of diffuse low-frequency components, which can render it difficult to detect a priori. Further, treatment of the signal with standard digital signal processing techniques cannot easily remove this scaling component. While several theoretical models have been introduced to explain the ubiquitous 1/f[Formula: see text] scaling component in neuroscientific data, we conjecture here that some experimental observations could be the result of such data analysis procedures.

  5. Signal reconstruction of surface waves on SASW measurement using Gaussian Derivative wavelet transform

    Science.gov (United States)

    Rosyidi, Sri; Taha, Mohd; Chik, Zamri; Ismail, Amiruddin

    2009-09-01

    Surface wave method consists of measurement and processing of the dispersive Rayleigh waves recorded from two or more vertical transducers. The dispersive phase data are inverted and the shear wave velocity versus depth is obtained. However, in case of residual soil, the reliable phase spectrum curve is difficult to be produced. Noises from nature and other human-made sources disturb the generated surface wave data. In this paper, a continuous wavelet transform based on mother wavelet of Gaussian Derivative was used to analyze seismic waves in different frequency and time. Time-frequency wavelet spectrum was employed to localize the interested seismic response spectrum of generated surface waves. It can also distinguish the fundamental mode of the surface wave from the higher modes of reflected body waves. The results presented in this paper showed that the wavelet analysis is able to determine reliable surface wave spectrum of sandy clayey residual soil.

  6. Metabolic and Signaling Functions of Cancer Cell-Derived Extracellular Vesicles.

    Science.gov (United States)

    Fonseca, P; Vardaki, I; Occhionero, A; Panaretakis, T

    2016-01-01

    Extracellular vesicles have gained tremendous attention in the recent years as a novel mechanism of cell to cell communication. There are several types of extracellular vesicles, including exosomes, microvesicles, exosome, like vesicles, apoptotic bodies that differ mainly in the mechanism of biogenesis and secretion. The most well studied type of extracellular vesicles are the exosomes which are endosome-derived vesicles with a diameter of 50-150nm and enriched in ESCRT proteins including Alix, TSG101, Hsp70, and tetraspanins. It is now well established that exosomes promote tumor growth, alter the tumor microenvironment, facilitate the dissemination of cancer cells in an organotropic manner, modulate immune responses, and mediate resistance to therapy. Exosomes have also been recently implicated in an emerging hallmark of cancer, the cancer cell metabolism. The metabolic state of the cell defines, to a certain extent, both the rate of secretion and the molecular content of tumor-derived exosomes. Furthermore, exosomes have been shown to possess intrinsic metabolic activity since they can synthesize ATP by glycolysis. It follows that exosomes carry a number of metabolic enzymes and metabolites, including lactate, PGE, LDH isoforms, pyruvate, and monocarboxylate transporters. Last but not the least, exosomes are implicated in fatty acid synthesis and cholesterol metabolism and are thought to be crucial for the transcellular metabolism procedure. Uptake of exosomes is thought to alter the intracellular metabolic state of the cell. In summary, we describe the state of the art on the role of metabolism in the secretion, uptake, and the biological effects of exosomes in the metabolism of recipient cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Lysophosphatidic acid signaling regulates the KLF9-PPARγ axis in human induced pluripotent stem cell-derived neurons.

    Science.gov (United States)

    Tsukahara, Tamotsu; Yamagishi, Shuhei; Matsuda, Yoshikazu; Haniu, Hisao

    2017-09-09

    Lysophosphatidic acid (LPA) is a lipid signaling molecule that plays several significant roles in the nervous system during development and injury. In this study, we differentiated human induced pluripotent stem cells (iPSCs) into neurons as an in vitro model to examine the specific effects of LPA. We demonstrated that LPA activates peroxisome proliferator-activated receptor gamma (PPARγ), a ligand-activated nuclear receptor, as well as its cognate receptor LPA1 on human iPSC-derived neurons to enhance proliferation and neurite outgrowth. Furthermore, we found that the gene expression of Kruppel-like factor 9 (KLF9), a member of the large KLF transcription factor family, was induced by LPA treatment. Knockdown of KLF9 decreased proliferation and neurite outgrowth in vehicle- and LPA-treated IPSC-derived neurons compared to cells expressing KLF9. In conclusion, LPA plays dual roles as a ligand mediator through the activation of cell surface G-coupled protein receptors and as an intracellular second messenger through the activation of PPARγ. We discuss the contribution of the LPA1-PPARγ-KLF9 axis to neurite outgrowth and proliferation in human iPSC-derived neurons. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. A CALM-derived nuclear export signal is essential for CALM-AF10-mediated leukemogenesis.

    Science.gov (United States)

    Conway, Amanda E; Scotland, Paula B; Lavau, Catherine P; Wechsler, Daniel S

    2013-06-06

    The t(10;11) chromosomal translocation gives rise to the CALM-AF10 fusion gene and is found in patients with aggressive and difficult-to-treat hematopoietic malignancies. CALM-AF10-driven leukemias are characterized by HOXA gene up-regulation and a global reduction in H3K79 methylation. DOT1L, the H3K79 methyltransferase, interacts with the octapeptide/leucine zipper domain of AF10, and this region has been shown to be necessary and sufficient for CALM-AF10-mediated transformation. However, the precise role of CALM in leukemogenesis remains unclear. Here, we show that CALM contains a nuclear export signal (NES) that mediates cytoplasmic localization of CALM-AF10 and is necessary for CALM-AF10-dependent transformation. Fusions of the CALM NES (NES(CALM)-AF10) or NES motifs from heterologous proteins (ABL1, Rev, PKIA, APC) in-frame with AF10 are sufficient to immortalize murine hematopoietic progenitors in vitro. The CALM NES is essential for CALM-AF10-dependent Hoxa gene up-regulation and aberrant H3K79 methylation, possibly by mislocalization of DOT1L. Finally, we observed that CALM-AF10 leukemia cells are selectively sensitive to inhibition of nuclear export by Leptomycin B. These findings uncover a novel mechanism of leukemogenesis mediated by the nuclear export pathway and support further investigation of the utility of nuclear export inhibitors as therapeutic agents for patients with CALM-AF10 leukemias.

  9. Focused attention vs. crossmodal signals paradigm: Deriving predictions from the time-window-of-integration model

    Directory of Open Access Journals (Sweden)

    Hans eColonius

    2012-08-01

    Full Text Available In the crossmodal signals paradigm (CSP participants are instructed to respond to a set of stimuli from different modalities, presented more or less simultaneously, as soon as a stimulus from any modality has been detected. In the focused attention paradigm (FAP, on the other hand, responses should only be made to a stimulus from a pre-defined target modality and stimuli from non-target modalities should be ignored. Whichever paradigm is being applied, a typical result is that responses tend to be faster to crossmodal stimuli than to unimodal stimuli, a phenomenon often referred to as 'crossmodal interaction'. Here we investigate predictions of the time-window-of-integration (TWIN modeling framework previously proposed by the authors. It is shown that TWIN makes specific qualitative and quantitative predictions on how the two paradigms differ with respect to the probability of multisensory integration and the amount of response enhancement, including the effect of stimulus intensity ('inverse effectiveness'. Introducing a decision-theoretic framework for TWIN further allows comparing the two paradigms with respect to the predicted optimal time window size and its dependence on the prior probability that the crossmodal stimulus information refers to the same event. In order to test these predictions, experimental studies that systematically compare crossmodal effects under stimulus conditions that are identical except for the CSP-FAP instruction should be performed in the future.

  10. Influence of zygomycete-derived D'orenone on IAA signalling in Tricholoma-spruce ectomycorrhiza.

    Science.gov (United States)

    Wagner, Katharina; Krause, Katrin; David, Anja; Kai, Marco; Jung, Elke-Martina; Sammer, Dominik; Kniemeyer, Olaf; Boland, Wilhelm; Kothe, Erika

    2016-09-01

    Despite the rising interest in microbial communication, only few studies relate to mycorrhization and the pool of potential morphogenic substances produced by the surrounding soil community. Here, we investigated the effect exerted by the C18 - ketone β-apo-13-carotenone, D'orenone, on the ectomycorrhizal basidiomycete Tricholoma vaccinum and its symbiosis with the economically important host tree, spruce (Picea abies). D'orenone is an early intermediate in the biosynthesis of morphogens in sexual development of mucoromycetes, the trisporoids. In the ectomycorrhizal fungus T. vaccinum, D'orenone increased the production and/or release of the phytohormone indole-3-acetic acid (IAA) which had been proposed to be involved in the mutual symbiosis. The induced expression of the fungal aldehyde dehydrogenase, Ald5 is associated with IAA synthesis and excretion. In the host tree, D'orenone modulated root architecture by increasing lateral root length and hypertrophy of root cortex cells, likely via changed IAA concentrations and flux. Thus, we report for the first time on carotenoid metabolites from soil fungi affecting both ectomycorrhizal partners. The data imply a complex network of functions for secondary metabolites which act in an inter-kingdom signalling in soil. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

  11. Squid-derived chitin oligosaccharides are a chemotactic signal during colonization by Vibrio fischeri.

    Science.gov (United States)

    Mandel, Mark J; Schaefer, Amy L; Brennan, Caitlin A; Heath-Heckman, Elizabeth A C; Deloney-Marino, Cindy R; McFall-Ngai, Margaret J; Ruby, Edward G

    2012-07-01

    Chitin, a polymer of N-acetylglucosamine (GlcNAc), is noted as the second most abundant biopolymer in nature. Chitin serves many functions for marine bacteria in the family Vibrionaceae ("vibrios"), in some instances providing a physical attachment site, inducing natural genetic competence, and serving as an attractant for chemotaxis. The marine luminous bacterium Vibrio fischeri is the specific symbiont in the light-emitting organ of the Hawaiian bobtail squid, Euprymna scolopes. The bacterium provides the squid with luminescence that the animal uses in an antipredatory defense, while the squid supports the symbiont's nutritional requirements. V. fischeri cells are harvested from seawater during each host generation, and V. fischeri is the only species that can complete this process in nature. Furthermore, chitin is located in squid hemocytes and plays a nutritional role in the symbiosis. We demonstrate here that chitin oligosaccharides produced by the squid host serve as a chemotactic signal for colonizing bacteria. V. fischeri uses the gradient of host chitin to enter the squid light organ duct and colonize the animal. We provide evidence that chitin serves a novel function in an animal-bacterial mutualism, as an animal-produced bacterium-attracting synomone.

  12. Monocyte-Derived Signals Activate Human Natural Killer Cells in Response to Leishmania Parasites

    Directory of Open Access Journals (Sweden)

    Helena Messlinger

    2018-01-01

    Full Text Available Activated natural killer (NK cells release interferon (IFN-γ, which is crucial for the control of intracellular pathogens such as Leishmania. In contrast to experimental murine leishmaniasis, the human NK cell response to Leishmania is still poorly characterized. Here, we investigated the interaction of human blood NK cells with promastigotes of different Leishmania species (Leishmania major, Leishmania mexicana, Leishmania infantum, and Leishmania donovani. When peripheral blood mononuclear cells or purified NK cells and monocytes (all derived from healthy blood donors from Germany without a history of leishmaniasis were exposed to promastigotes, NK cells showed increased surface expression of the activation marker CD69. The extent of this effect varied depending on the Leishmania species; differences between dermotropic and viscerotropic L. infantum strains were not observed. Upregulation of CD69 required direct contact between monocytes and Leishmania and was partly inhibitable by anti-interleukin (IL-18. Unexpectedly, IL-18 was undetectable in most of the supernatants (SNs of monocyte/parasite cocultures. Confocal fluorescence microscopy of non-permeabilized cells revealed that Leishmania-infected monocytes trans-presented IL-18 to NK cells. Native, but not heat-treated SNs of monocyte/Leishmania cocultures also induced CD69 on NK cells, indicating the involvement of a soluble heat-labile factor other than IL-18. A role for the NK cell-activating cytokines IL-1β, IL-2, IL-12, IL-15, IL-21, and IFN-α/β was excluded. The increase of CD69 was not paralleled by NK cell IFN-γ production or enhanced cytotoxicity. However, prior exposure of NK cells to Leishmania parasites synergistically increased their IFN-γ release in response to IL-12, which was dependent on endogenous IL-18. CD1c+ dendritic cells were identified as possible source of Leishmania-induced IL-12. Finally, we observed that direct contact between Leishmania and NK cells

  13. Penile vibratory stimulation in the recovery of urinary continence and erectile function after nerve‐sparing radical prostatectomy: a randomized, controlled trial

    National Research Council Canada - National Science Library

    Fode, Mikkel; Borre, Michael; Ohl, Dana A; Lichtbach, Jonas; Sønksen, Jens

    2014-01-01

    To examine the effect of penile vibratory stimulation (PVS) in the preservation and restoration of erectile function and urinary continence in conjunction with nerve-sparing radical prostatectomy (RP...

  14. Pam2 lipopeptides systemically increase myeloid-derived suppressor cells through TLR2 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Maruyama, Akira; Shime, Hiroaki, E-mail: shime@med.hokudai.ac.jp; Takeda, Yohei; Azuma, Masahiro; Matsumoto, Misako; Seya, Tsukasa, E-mail: seya-tu@pop.med.hokudai.ac.jp

    2015-02-13

    Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that exhibit potent immunosuppressive activity. They are increased in tumor-bearing hosts and contribute to tumor development. Toll-like receptors (TLRs) on MDSCs may modulate the tumor-supporting properties of MDSCs through pattern-recognition. Pam2 lipopeptides represented by Pam2CSK4 serve as a TLR2 agonist to exert anti-tumor function by dendritic cell (DC)-priming that leads to NK cell activation and cytotoxic T cell proliferation. On the other hand, TLR2 enhances tumor cell progression/invasion by activating tumor-infiltrating macrophages. How MDSCs respond to TLR2 agonists has not yet been determined. In this study, we found intravenous administration of Pam2CSK4 systemically up-regulated the frequency of MDSCs in EG7 tumor-bearing mice. The frequency of tumor-infiltrating MDSCs was accordingly increased in response to Pam2CSK4. MDSCs were not increased by Pam2CSK4 stimuli in TLR2 knockout (KO) mice. Adoptive transfer experiments using CFSE-labeled MDSCs revealed that the TLR2-positive MDSCs survived long in tumor-bearing mice in response to Pam2CSK4 treatment. Since the increased MDSC population sustained immune-suppressive properties, our study suggests that Pam2CSK4-triggered TLR2 activation enhances the MDSC potential and suppress antitumor immune response in tumor microenvironment. - Highlights: • Pam2CSK4 administration induces systemic accumulation of CD11b{sup +}Gr1{sup +} MDSCs. • TLR2 is essential for Pam2CSK4-induced accumulation of CD11b{sup +}Gr1{sup +} MDSCs. • Pam2CSK4 supports survival of CD11b{sup +}Gr1{sup +} MDSCs in vivo.

  15. Antrodia cinnamomea Prevents Obesity, Dyslipidemia, and the Derived Fatty Liver via Regulating AMPK and SREBP Signaling.

    Science.gov (United States)

    Peng, Chiung-Huei; Yang, Mon-Yuan; Yang, Yi-Sun; Yu, Chieh-Chou; Wang, Chau-Jong

    2017-01-01

    Antrodia cinnamomea (AC), a protogenic fungus that only grows on the heartwood of endemic Cinnamomum kanehirae Hayata in Taiwan, is used to treat a variety of illness including liver disease. However, little is known about the benefit of AC against obesity and the related hepatic disorder. Using high-fat-diet (HFD) feed mice, we aimed to investigate whether the extract of AC (ACE) could reduce excessive weight, body fat, and serum lipids and prevent the development of non-alcoholic fatty liver (NAFLD). C57BL/6 mice were divided into five groups fed with different diets: control, HFD, and HFD with 0.5%, 1%, or 2% of ACE, respectively. After 10 weeks the animals were sacrificed, with serum and liver collected. HFD-induced elevation of body weight gain, body fat deposition, and serum free fatty acid (FFA), triacylglycerol (TGs), total cholesterol, and ratio of LDL cholesterol (LDL-C)/HDL cholesterol (HDL-C), were significantly restored by ACE. ACE reduced aspartate aminotransferase (AST), alanine aminotransferase (ALT), and hepatic lipid deposits increased by HFD. ACE increased p-AMP activated protein kinase (pAMPK) but decreased Sterol regulatory element binding protein (SREBP), fatty acid synthase (FAS), 1-acylglycerol-3-phosphate acyltransferase (AGPAT), and 3-hydroxy-3-methylglutaryl-coenzyme A (HMGCoA) reductase. The chemical analysis reveals ACE is full of triterpenes, the most abundant of which is Antcin K, followed by sulphurenic acid, eburicoic acid, antcin C, dehydrosulphurenic acid, antcin B, and propanoic acid. In conclusion, ACE should be used to prevent obesity and derived fatty liver. The applicability of ACE on NAFLD deserves further investigation.

  16. Thymus-deriving natural regulatory T cell generation in vitro: role of the source of activation signals.

    Science.gov (United States)

    Bieńkowska, Anna; Kiernozek, Ewelina; Kozlowska, Ewa; Zarzycki, Michał; Drela, Nadzieja

    2014-12-01

    In this research we have examined different sources of activation signals in order to optimize culture conditions for in vitro generation of thymus-deriving natural regulatory T cells (nTregs). We have established a novel model using JAWS II dendritic cell line of immature phenotype and compared it to commonly used methods for the generation of Tregs from peripheral lymphoid organs or blood T cells. In our model the first activation signal is provided by anti-CD3 monoclonal antibodies while the second is delivered by costimulatory molecules expressed on JAWS II cells. The presence of JAWS II cells co-cultured in vitro with unsorted thymocytes directly isolated from the thymus gland creates environment favoring SP CD4+ differentiation, provides the apoptotic cells clearance, maintains the survival of thymocytes and facilitate nTreg generation. Moreover the usage of immature dendritic cells stimuli enables to conduct research on agents affecting nTreg survival, proliferation and development in conditions of cell-to-cell contact of undifferentiated thymocytes with dendritic cells. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Effect of Mesenchymal Stem Cells and a Novel Curcumin Derivative on Notch1 Signaling in Hepatoma Cell Line

    Directory of Open Access Journals (Sweden)

    Mohamed Talaat Abdel Aziz

    2013-01-01

    Full Text Available This study was conducted to evaluate the effect of mesenchymal stem cells (MSCs and a novel curcumin derivative (NCD on HepG2 cells (hepatoma cell line and to investigate their effect on Notch1 signaling pathway target genes. HepG2 cells were divided into HepG2 control group, HepG2 cells treated with MSC conditioned medium (MSCs CM, HepG2 cells treated with a NCD, HepG2 cells treated with MSCs CM and NCD, and HepG2 cells treated with MSCs CM (CM of MSCs pretreated with a NCD. Expression of Notch1, Hes1, VEGF, and cyclin D1 was assessed by real-time, reverse transcription-polymerase chain reaction (RT-PCR in HepG2 cells. In addition, HepG2 proliferation assay was performed in all groups. Notch1 and its target genes (Hes1 and cyclin D1 were downregulated in all treated groups with more suppressive effect in the groups treated with both MSCs and NCD. Also, treated HepG2 cells showed significant decrease in cell proliferation rate. These data suggest that modulation of Notch1 signaling pathway by MSCs and/or NCD can be considered as a therapeutic target in HCC.

  18. Stroma cell-derived factor-1α signaling enhances calcium transients and beating frequency in rat neonatal cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Ielham Hadad

    Full Text Available Stroma cell-derived factor-1α (SDF-1α is a cardioprotective chemokine, acting through its G-protein coupled receptor CXCR4. In experimental acute myocardial infarction, administration of SDF-1α induces an early improvement of systolic function which is difficult to explain solely by an anti-apoptotic and angiogenic effect. We wondered whether SDF-1α signaling might have direct effects on calcium transients and beating frequency.Primary rat neonatal cardiomyocytes were culture-expanded and characterized by immunofluorescence staining. Calcium sparks were studied by fluorescence microscopy after calcium loading with the Fluo-4 acetoxymethyl ester sensor. The cardiomyocyte enriched cellular suspension expressed troponin I and CXCR4 but was vimentin negative. Addition of SDF-1α in the medium increased cytoplasmic calcium release. The calcium response was completely abolished by using a neutralizing anti-CXCR4 antibody and partially suppressed and delayed by preincubation with an inositol triphosphate receptor (IP3R blocker, but not with a ryanodine receptor (RyR antagonist. Calcium fluxes induced by caffeine, a RyR agonist, were decreased by an IP3R blocker. Treatment with forskolin or SDF-1α increased cardiomyocyte beating frequency and their effects were additive. In vivo, treatment with SDF-1α increased left ventricular dP/dtmax.These results suggest that in rat neonatal cardiomyocytes, the SDF-1α/CXCR4 signaling increases calcium transients in an IP3-gated fashion leading to a positive chronotropic and inotropic effect.

  19. Lawsone derivatives target the Wnt/β-catenin signaling pathway in multidrug-resistant acute lymphoblastic leukemia cells.

    Science.gov (United States)

    Hamdoun, Sami; Fleischer, Edmond; Klinger, Anette; Efferth, Thomas

    2017-12-15

    Multidrug resistance (MDR) represents a serious problem in cancer treatment. One strategy to overcome this obstacle is to identify agents that are selectively lethal to MDR cells. The aim of this study was to discover novel compounds against MDR leukemia and to determine the molecular mechanisms behind collateral sensitivity. A library of 1162 compounds was tested against parental, drug-sensitive CCRF-CEM cells using the resazurin assay. A total of 302 compounds showed reasonable activity (less than 50% cell viability). Eleven out of 30 lawsone derivatives revealed considerable collateral sensitivity in MDR P-glycoprotein (Pgp)-overexpressing CEM/ADR5000 cells. They reduced β-catenin activity in a Wnt/β-catenin reporter cell line. Their activities significantly correlated with apolar desolvation (R = 0.819). Compound (1) (3-hydroxy-1,4-dioxo-N-phenyl-naphthalene-2-carboxamide) was the most active compound and dose-dependently down-regulated protein expression of β-catenin, c-MYC, Pgp and Frizzled 7. By molecular docking, we predicted that compound (1) bound to the palmitoyl-binding groove of the cysteine-rich domain of Frizzled-7 and Frizzled-8. Compound (1) neither stimulated ATPase activity of Pgp nor reactive oxygen species generation, both of which have been previously described as possible mechanisms of collateral sensitivity. Instead, we found that Wnt/β-catenin signaling was selectively inhibited in CEM/ADR5000 cells, but not in CCRF-CEM cells. In conclusion, we found for the first time that the inhibition of Wnt/β-catenin signaling may represent a novel molecular mechanism of collateral sensitivity in MDR cells. Wnt/β-catenin signaling, therefore, represents a potential therapeutic target for the selective killing of Pgp-mediated MDR. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Genome-wide identification of Bcl11b gene targets reveals role in brain-derived neurotrophic factor signaling.

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    Bin Tang

    Full Text Available B-cell leukemia/lymphoma 11B (Bcl11b is a transcription factor showing predominant expression in the striatum. To date, there are no known gene targets of Bcl11b in the nervous system. Here, we define targets for Bcl11b in striatal cells by performing chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq in combination with genome-wide expression profiling. Transcriptome-wide analysis revealed that 694 genes were significantly altered in striatal cells over-expressing Bcl11b, including genes showing striatal-enriched expression similar to Bcl11b. ChIP-seq analysis demonstrated that Bcl11b bound a mixture of coding and non-coding sequences that were within 10 kb of the transcription start site of an annotated gene. Integrating all ChIP-seq hits with the microarray expression data, 248 direct targets of Bcl11b were identified. Functional analysis on the integrated gene target list identified several zinc-finger encoding genes as Bcl11b targets, and further revealed a significant association of Bcl11b to brain-derived neurotrophic factor/neurotrophin signaling. Analysis of ChIP-seq binding regions revealed significant consensus DNA binding motifs for Bcl11b. These data implicate Bcl11b as a novel regulator of the BDNF signaling pathway, which is disrupted in many neurological disorders. Specific targeting of the Bcl11b-DNA interaction could represent a novel therapeutic approach to lowering BDNF signaling specifically in striatal cells.

  1. Vibratory stimulation from powered-toothbrush: A novel approach for orthodontic pain reduction after initial archwire placement

    Directory of Open Access Journals (Sweden)

    Pradeep Raghav

    2015-01-01

    Full Text Available Introduction: Vibratory stimulation has been reported as an effective means in reducing the orthodontic pain. The aim of this study was to evaluate the effectiveness of vibratory stimulation from powered-toothbrushes as a noninvasive and nonpharmacological method of reducing pain caused after initial archwire placement and to compare it with other common modalities of management. Materials and Methods: This clinical trial included 75 patients of age 13–25 years, scheduled for fixed mechanotherapy. Patients were divided into five groups: Control, placebo multivitamin, paracetamol, chewing-gum (Cg, and powered-toothbrush. After placement of 0.016″ Nickel Titanium initial archwire (upper/lower in each patient, the discomfort perceived at 2 h, 6 h, bedtime, 24 h, 2 days, 3 days, and 7 days were marked individually using Wong-Baker (0–5 and numeric (0–10 pain rating scales. Kruskal–Wallis test, Friedman test, unpaired t-test were used for statistical analysis. Results: Vibratory stimulation from powered-toothbrushes effectively reduced pain after initial archwire placement. It did not alter the pattern of pain perception, but significantly reduced the overall intensity of pain at each time interval. Cg was not found effective enough to be recommended as a routine treatment modality. Conclusion: Powered-toothbrushes can be recommended as a nonpharmacological and noninvasive substitute for nonsteroidal anti-inflammatory drugs for effective pain reduction in the clinical practice.

  2. Perception of Frequency, Amplitude and Azimuth of a Vibratory Dipole-Source by the Octavolateralis System of Goldfish (Carassius auratus)

    Science.gov (United States)

    Dailey, Deena D.; Braun, Christopher B.

    2011-01-01

    Goldfish (Carassius auratus) were conditioned to suppress respiration to a 40 Hz vibratory source and subsequently tested for stimulus generalization to frequency, stimulus amplitude and position (azimuth). Animals completely failed to generalize to frequencies separated by octave intervals, both lesser and greater than the CS. However they did appear to generalize weakly to an aerial loudspeaker stimulus of the same frequency (40 Hz) after conditioning with an underwater vibratory source. Animals had a gradually decreasing amount of generalization to amplitude changes, suggesting a perceptual dimension of loudness. Animals generalized largely or completely to the same underwater source presented at a range of source azimuths. When these azimuths were presented at a transect of 3 cm, some animals did show decrements in generalization, while others did not. This suggests that although azimuth may be perceived more saliently at distances closer to a dipole source, perception of position is not immediately salient in conditioned vibratory source detection. Differential responding to test stimuli located towards the head or tail suggests the presence of perceptual differences between sources that are rostral or caudal with respect to the position of the animal or perhaps the head. PMID:21574689

  3. Signaling via class IA Phosphoinositide 3-kinases (PI3K in human, breast-derived cell lines.

    Directory of Open Access Journals (Sweden)

    Veronique Juvin

    Full Text Available We have addressed the differential roles of class I Phosphoinositide 3-kinases (PI3K in human breast-derived MCF10a (and iso-genetic derivatives and MDA-MB 231 and 468 cells. Class I PI3Ks are heterodimers of p110 catalytic (α, β, δ and γ and p50-101 regulatory subunits and make the signaling lipid, phosphatidylinositol (3,4,5-trisphosphate (PtdIns(3,4,5P3 that can activate effectors, eg protein kinase B (PKB, and responses, eg migration. The PtdIns(3,4,5P3-3-phosphatase and tumour-suppressor, PTEN inhibits this pathway. p110α, but not other p110s, has a number of onco-mutant variants that are commonly found in cancers. mRNA-seq data shows that MCF10a cells express p110β>>α>δ with undetectable p110γ. Despite this, EGF-stimulated phosphorylation of PKB depended upon p110α-, but not β- or δ- activity. EGF-stimulated chemokinesis, but not chemotaxis, was also dependent upon p110α, but not β- or δ- activity. In the presence of single, endogenous alleles of onco-mutant p110α (H1047R or E545K, basal, but not EGF-stimulated, phosphorylation of PKB was increased and the effect of EGF was fully reversed by p110α inhibitors. Cells expressing either onco-mutant displayed higher basal motility and EGF-stimulated chemokinesis.This latter effect was, however, only partially-sensitive to PI3K inhibitors. In PTEN(-/- cells, basal and EGF-stimulated phosphorylation of PKB was substantially increased, but the p110-dependency was variable between cell types. In MDA-MB 468s phosphorylation of PKB was significantly dependent on p110β, but not α- or δ- activity; in PTEN(-/- MCF10a it remained, like the parental cells, p110α-dependent. Surprisingly, loss of PTEN suppressed basal motility and EGF-stimulated chemokinesis. These results indicate that; p110α is required for EGF signaling to PKB and chemokinesis, but not chemotaxis; onco-mutant alleles of p110α augment signaling in the absence of EGF and may increase motility, in part, via acutely

  4. System Modeling of a MEMS Vibratory Gyroscope and Integration to Circuit Simulation.

    Science.gov (United States)

    Kwon, Hyukjin J; Seok, Seyeong; Lim, Geunbae

    2017-11-18

    Recently, consumer applications have dramatically created the demand for low-cost and compact gyroscopes. Therefore, on the basis of microelectromechanical systems (MEMS) technology, many gyroscopes have been developed and successfully commercialized. A MEMS gyroscope consists of a MEMS device and an electrical circuit for self-oscillation and angular-rate detection. Since the MEMS device and circuit are interactively related, the entire system should be analyzed together to design or test the gyroscope. In this study, a MEMS vibratory gyroscope is analyzed based on the system dynamic modeling; thus, it can be mathematically expressed and integrated into a circuit simulator. A behavioral simulation of the entire system was conducted to prove the self-oscillation and angular-rate detection and to determine the circuit parameters to be optimized. From the simulation, the operating characteristic according to the vacuum pressure and scale factor was obtained, which indicated similar trends compared with those of the experimental results. The simulation method presented in this paper can be generalized to a wide range of MEMS devices.

  5. Two Novel Measurements for the Drive-Mode Resonant Frequency of a Micromachined Vibratory Gyroscope

    Directory of Open Access Journals (Sweden)

    Ancheng Wang

    2013-11-01

    Full Text Available To investigate the drive-mode resonance frequency of a micromachined vibratory gyroscope (MVG, one needs to measure it accurately and efficiently. The conventional approach to measure the resonant frequency is by performing a sweep frequency test and spectrum analysis. The method is time-consuming and inconvenient because of the requirements of many test points, a lot of data storage and off-line analyses. In this paper, we propose two novel measurement methods, the search method and track method, respectively. The former is based on the magnitude-frequency characteristics of the drive mode, utilizing a one-dimensional search technique. The latter is based on the phase-frequency characteristics, applying a feedback control loop. Their performances in precision, noise resistivity and efficiency are analyzed through detailed simulations. A test system is implemented based on a field programmable gate array (FPGA and experiments are carried out. By comparing with the common approach, feasibility and superiorities of the proposed methods are validated. In particular, significant efficiency improvements are achieved whereby the conventional frequency method consumes nearly 5,000 s to finish a measurement, while only 5 s is needed for the track method and 1 s for the search method.

  6. System Modeling of a MEMS Vibratory Gyroscope and Integration to Circuit Simulation

    Directory of Open Access Journals (Sweden)

    Hyukjin J. Kwon

    2017-11-01

    Full Text Available Recently, consumer applications have dramatically created the demand for low-cost and compact gyroscopes. Therefore, on the basis of microelectromechanical systems (MEMS technology, many gyroscopes have been developed and successfully commercialized. A MEMS gyroscope consists of a MEMS device and an electrical circuit for self-oscillation and angular-rate detection. Since the MEMS device and circuit are interactively related, the entire system should be analyzed together to design or test the gyroscope. In this study, a MEMS vibratory gyroscope is analyzed based on the system dynamic modeling; thus, it can be mathematically expressed and integrated into a circuit simulator. A behavioral simulation of the entire system was conducted to prove the self-oscillation and angular-rate detection and to determine the circuit parameters to be optimized. From the simulation, the operating characteristic according to the vacuum pressure and scale factor was obtained, which indicated similar trends compared with those of the experimental results. The simulation method presented in this paper can be generalized to a wide range of MEMS devices.

  7. Separation of water from metal working emulsions by ultrafiltration using vibratory membranes.

    Science.gov (United States)

    Moulai-Mostefa, Nadji; Frappart, Matthieu; Akoum, Omar; Ding, Luhui; Jaffrin, Michel Y

    2010-05-15

    In this paper, we investigate the application of a vibratory shear-enhanced filtration system (VSEP) to separation of water from oil-in-water emulsions. The VSEP module consists in an annular membrane of 500 cm(2) area which oscillates azimuthally in its own plane with an amplitude depending upon frequency. Polyethersulfone (PES) membranes of 50 and 20 kDa were used. Test fluids consisted of oil-in-water emulsion at an oil concentration of 4% prepared from a concentrated cutting fluid. The critical flux for stable operation was investigated by increasing the permeate flux in steps while monitoring the transmembrane pressure (TMP). With a 50 kDa membrane the flux increased nonlinearly with TMP and reached 250 L h(-1)m(-2) at a TMP of 1500 kPa while permeate turbidity decayed from 1.8 to 0.9 NTU above 600 kPa from an initial emulsion turbidity of 21,900 NTU. With the 20 kDa membrane, the flux increased linearly with TMP until 1600 kPa, but the oil concentration in permeate became negligible (turbidity near zero NTU). Concentration tests showed that the flux decreased linearly with ln(VRR) where VRR is the volume reduction ratio while permeate turbidity increased exponentially to 25NTU above a VRR of 4. This work confirms the high performance of the VSEP for oil separation from water in metal working emulsions. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  8. Penile vibratory stimulation and electroejaculation before anticancer therapy in two pubertal boys.

    Science.gov (United States)

    Schmiegelow, M L; Sommer, P; Carlsen, E; Sønksen, J O; Schmiegelow, K; Müller, J R

    1998-01-01

    Because more than 70% of children with cancer become long-term survivors, more emphasis is put on reducing late effects. Cryopreservation of semen and the intracytoplasmic sperm injection technique makes it possible to obtain pregnancy with very poor sperm quality. Two new semen retrieval methods are described that are applicable in pubertal boys with a fertility potential, although not psychologically ready to produce a semen sample, who are likely to become infertile because of anticancer therapy. Two pubertal boys (aged 14 and 15 years) had a late testicular relapse of pre-B acute lymphoblastic leukemia and Hodgkin disease, stage II, respectively. In patient 1, penile vibratory stimulation (PVS) was tried under general anesthesia without success and electroejaculation (EEJ) was performed. Before alkylating chemotherapy and testicular irradiation, PVS was performed with success in patient 2. An antegrade ejaculate of 0.7 ml with 1% motile spermatozoa and an retrograde ejaculate with 1.6 x 10(6)/ml spermatozoa (5% with fair motility) was obtained from patient 1. An antegrade ejaculate of 1.5 ml with 2.5 x 10(6)/ml spermatozoa (29% with fair motility) was obtained from patient 2. PVS should be the first choice of treatment because it is noninvasive, simple, and easily applied. Because EEJ requires general anesthesia, it should be used as a second option.

  9. Penile vibratory stimulation in the treatment of post-prostatectomy incontinence

    DEFF Research Database (Denmark)

    Fode, Mikkel; Sønksen, Jens

    2015-01-01

    AIMS: To examine penile vibratory stimulation (PVS) in the treatment of post-prostatectomy urinary incontinence (UI). METHODS: Patients with post-prostatectomy UI were included in a 12-week trial. A 24-hr pad test and a 72-hr voiding diary were collected at baseline. Participants were randomized...... men were available for analyses. The difference in the change on the pad test between the groups did not reach statistical significance at 6 weeks (P = 0.13) while the change in incontinence episodes between groups approached statistical significance (P = 0.052). However, there was a median reduction...... of -33 g (P = 0.021) on the pad test and a median reduction in daily incontinence episodes of -1 (P = 0.023) in group 1 at 6 weeks. At 12 weeks, group 2 had a median decrease on the pad test of -8 g (P = 0.10) and no change in incontinence episodes. A pooled analysis showed a decline on the pad test...

  10. The nature of alarm communication in Constrictotermes cyphergaster (Blattodea: Termitoidea: Termitidae): the integration of chemical and vibroacoustic signals.

    Science.gov (United States)

    Cristaldo, Paulo F; Jandák, Vojtĕch; Kutalová, Kateřina; Rodrigues, Vinícius B; Brothánek, Marek; Jiříček, Ondřej; DeSouza, Og; Šobotník, Jan

    2015-11-04

    Alarm signalling is of paramount importance to communication in all social insects. In termites, vibroacoustic and chemical alarm signalling are bound to operate synergistically but have never been studied simultaneously in a single species. Here, we inspected the functional significance of both communication channels in Constrictotermes cyphergaster (Termitidae: Nasutitermitinae), confirming the hypothesis that these are not exclusive, but rather complementary processes. In natural situations, the alarm predominantly attracts soldiers, which actively search for the source of a disturbance. Laboratory testing revealed that the frontal gland of soldiers produces a rich mixture of terpenoid compounds including an alarm pheromone. Extensive testing led to identification of the alarm pheromone being composed of abundant monoterpene hydrocarbons (1S)-α-pinene and myrcene, along with a minor component, (E)-β-ocimene. The vibratory alarm signalling consists of vibratory movements evidenced as bursts; a series of beats produced predominantly by soldiers. Exposing termite groups to various mixtures containing the alarm pheromone (crushed soldier heads, frontal gland extracts, mixture of all monoterpenes, and the alarm pheromone mixture made of standards) resulted in significantly higher activity in the tested groups and also increased intensity of the vibratory alarm communication, with the responses clearly dose-dependent. Lower doses of the pheromone provoked higher numbers of vibratory signals compared to higher doses. Higher doses induced long-term running of all termites without stops necessary to perform vibratory behaviour. Surprisingly, even crushed worker heads led to low (but significant) increases in the alarm responses, suggesting that other unknown compound in the worker's head is perceived and answered by termites. Our results demonstrate the existence of different alarm levels in termites, with lower levels being communicated through vibratory signals, and

  11. The nature of alarm communication in Constrictotermes cyphergaster (Blattodea: Termitoidea: Termitidae: the integration of chemical and vibroacoustic signals

    Directory of Open Access Journals (Sweden)

    Paulo F. Cristaldo

    2015-12-01

    Full Text Available Alarm signalling is of paramount importance to communication in all social insects. In termites, vibroacoustic and chemical alarm signalling are bound to operate synergistically but have never been studied simultaneously in a single species. Here, we inspected the functional significance of both communication channels in Constrictotermes cyphergaster (Termitidae: Nasutitermitinae, confirming the hypothesis that these are not exclusive, but rather complementary processes. In natural situations, the alarm predominantly attracts soldiers, which actively search for the source of a disturbance. Laboratory testing revealed that the frontal gland of soldiers produces a rich mixture of terpenoid compounds including an alarm pheromone. Extensive testing led to identification of the alarm pheromone being composed of abundant monoterpene hydrocarbons (1S-α-pinene and myrcene, along with a minor component, (E-β-ocimene. The vibratory alarm signalling consists of vibratory movements evidenced as bursts; a series of beats produced predominantly by soldiers. Exposing termite groups to various mixtures containing the alarm pheromone (crushed soldier heads, frontal gland extracts, mixture of all monoterpenes, and the alarm pheromone mixture made of standards resulted in significantly higher activity in the tested groups and also increased intensity of the vibratory alarm communication, with the responses clearly dose-dependent. Lower doses of the pheromone provoked higher numbers of vibratory signals compared to higher doses. Higher doses induced long-term running of all termites without stops necessary to perform vibratory behaviour. Surprisingly, even crushed worker heads led to low (but significant increases in the alarm responses, suggesting that other unknown compound in the worker's head is perceived and answered by termites. Our results demonstrate the existence of different alarm levels in termites, with lower levels being communicated through

  12. The nature of alarm communication in Constrictotermes cyphergaster (Blattodea: Termitoidea: Termitidae): the integration of chemical and vibroacoustic signals

    Science.gov (United States)

    Cristaldo, Paulo F.; Jandák, Vojtĕch; Kutalová, Kateřina; Rodrigues, Vinícius B.; Brothánek, Marek; Jiříček, Ondřej; DeSouza, Og; Šobotník, Jan

    2015-01-01

    ABSTRACT Alarm signalling is of paramount importance to communication in all social insects. In termites, vibroacoustic and chemical alarm signalling are bound to operate synergistically but have never been studied simultaneously in a single species. Here, we inspected the functional significance of both communication channels in Constrictotermes cyphergaster (Termitidae: Nasutitermitinae), confirming the hypothesis that these are not exclusive, but rather complementary processes. In natural situations, the alarm predominantly attracts soldiers, which actively search for the source of a disturbance. Laboratory testing revealed that the frontal gland of soldiers produces a rich mixture of terpenoid compounds including an alarm pheromone. Extensive testing led to identification of the alarm pheromone being composed of abundant monoterpene hydrocarbons (1S)-α-pinene and myrcene, along with a minor component, (E)-β-ocimene. The vibratory alarm signalling consists of vibratory movements evidenced as bursts; a series of beats produced predominantly by soldiers. Exposing termite groups to various mixtures containing the alarm pheromone (crushed soldier heads, frontal gland extracts, mixture of all monoterpenes, and the alarm pheromone mixture made of standards) resulted in significantly higher activity in the tested groups and also increased intensity of the vibratory alarm communication, with the responses clearly dose-dependent. Lower doses of the pheromone provoked higher numbers of vibratory signals compared to higher doses. Higher doses induced long-term running of all termites without stops necessary to perform vibratory behaviour. Surprisingly, even crushed worker heads led to low (but significant) increases in the alarm responses, suggesting that other unknown compound in the worker's head is perceived and answered by termites. Our results demonstrate the existence of different alarm levels in termites, with lower levels being communicated through vibratory

  13. Coral-Derived Compound WA-25 Inhibits Angiogenesis by Attenuating the VEGF/VEGFR2 Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Shih-Wei Lin

    2015-02-01

    Full Text Available Background: WA-25 (dihydroaustrasulfone alcohol, a synthetic derivative of marine compound WE-2 suppresses atherosclerosis in rats by reducing neointima formation. Because angiogenesis plays a critical role in the pathogenesis of atherosclerosis, the present study investigated the angiogenic function and mechanism of WA-25. Methods: The angiogenic effect of WA-25 was evaluated using a rat aortic ring assay and transgenic zebrafish models were established using transgenic Tg(fli-1:EGFPy1 and Tg(kdrl:mCherryci5-fli1a:negfpy7 zebrafish embryos. In addition, the effect of WA-25 on distinct angiogenic processes, including matrix metalloproteinase (MMP expression, endothelial cell proliferation and migration, as well as tube formation, was studied using human umbilical vein endothelial cells (HUVECs. The effect of WA-25 on the endothelial vascular endothelial growth factor (VEGF signaling pathway was elucidated using qRT-PCR, immunoblot analysis, immunofluorescence and flow cytometric analyses. Results: The application of WA-25 perturbed the development of intersegmental vessels in transgenic zebrafish. Moreover, WA-25 potently suppressed microvessel sprouting in organotypic rat aortic rings. Among cultured endothelial cells, WA-25 significantly and dose-dependently inhibited MMP-2/MMP-9 expression, proliferation, migration and tube formation in HUVECs. Mechanistic studies revealed that WA-25 significantly reduced the VEGF release by reducing VEGF expression at the mRNA and protein levels. In addition, WA-25 reduced surface VEGF receptor 2 (VEGFR2/Flk-1 expression by repressing the VEGFR2 mRNA level. Finally, an exogenous VEGF supply partially rescued the WA-25-induced angiogenesis blockage in vitro and in vivo. Conclusions: WA-25 is a potent angiogenesis inhibitor that acts through the down-regulation of VEGF and VEGFR2 in endothelial cells. General Significance: WA-25 may constitute a novel anti-angiogenic drug that acts by targeting endothelial

  14. Brain-derived neurotrophic factor signaling plays a role in resilience to stress promoted by isoquinoline in defeated mice.

    Science.gov (United States)

    Pesarico, Ana Paula; Rosa, Suzan G; Martini, Franciele; Goulart, Tales A; Zeni, Gilson; Nogueira, Cristina Wayne

    2017-11-01

    Certain stressful life events have been associated with the onset of depression. This study aims to investigate if 7-fluoro-1,3-diphenylisoquinoline-1-amine (FDPI) is effective against social avoidance induced by social defeat stress model in mice. Furthermore, it was investigated the effects of FDPI in the mouse prefrontal cortical plasticity-related proteins and some parameters of toxicity. Adult Swiss mice were subjected to social defeat stress for 10 days. Two protocols with FDPI were carried out: 1- FDPI (25 mg/kg, intragastric) was administered to mice 24 h after the last social defeat stress episode; 2- FDPI (1-25 mg/kg, intragastric) was administered to mice once a day for 10 days concomitant with the social defeat stress. The mice performed social avoidance and locomotor tests. The prefrontal cortical protein contents of kinase B (Akt), extracellular signal-regulated kinase (ERK), cAMP-response element binding protein (CREB), pro-brain-derived neurotrophic factor (proBDNF), p75NTR, neuronal nuclear protein (NeuN) and nuclear factor-κB (NF-κB) were determined in mice. A single administration of FDPI (25 mg/kg) partially protected against social avoidance induced by stress in mice. Repeated administration of FDPI (25 mg/kg) protected against social avoidance induced by stress in mice. Social defeat stress decreased the protein contents of p75NTR, NeuN and the pERK/ERK ratio but increased those of proBDNF and the pCREB/CREB ratio, without changing that of NF-κB. Repeated administration of FDPI modulated signaling pathways altered by social defeat stress in mice. The present findings demonstrate that FDPI promoted resilience to stress in mice. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Adiponectin enhances osteogenic differentiation in human adipose-derived stem cells by activating the APPL1-AMPK signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Tong; Wu, Yu-wei; Lu, Hui; Guo, Yuan [Second Dental Center, Peking University School and Hospital of Stomatology, Beijing (China); National Engineering Laboratory for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology, Beijing (China); Tang, Zhi-hui, E-mail: tang_zhihui@live.cn [Second Dental Center, Peking University School and Hospital of Stomatology, Beijing (China); National Engineering Laboratory for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology, Beijing (China)

    2015-05-29

    Human adipose-derived stem cells (hASCs) are multipotent progenitor cells with multi-lineage differentiation potential including osteogenesis and adipogenesis. While significant progress has been made in understanding the transcriptional control of hASC fate, little is known about how hASC differentiation is regulated by the autocrine loop. The most abundant adipocytokine secreted by adipocytes, adiponectin (APN) plays a pivotal role in glucose metabolism and energy homeostasis. Growing evidence suggests a positive association between APN and bone formation yet little is known regarding the direct effects of APN on hASC osteogenesis. Therefore, this study was designed to investigate the varied osteogenic effects and regulatory mechanisms of APN in the osteogenic commitment of hASCs. We found that APN enhanced the expression of osteoblast-related genes in hASCs, such as osteocalcin, alkaline phosphatase, and runt-related transcription factor-2 (Runx2, also known as CBFa1), in a dose- and time-dependent manner. This was further confirmed by the higher expression levels of alkaline phosphatase and increased formation of mineralization nodules, along with the absence of inhibition of cell proliferation. Importantly, APN at 1 μg/ml was the optimal concentration, resulting in maximum deposition of calcium nodules, and was significant superior to bone morphogenetic protein 2. Mechanistically, we found for the first time that APN increased nuclear translocation of the leucine zipper motif (APPL)-1 as well as AMP-activated protein kinase (AMPK) phosphorylation, which were reversed by pretreatment with APPL1 siRNA. Our results indicate that APN promotes the osteogenic differentiation of hASCs by activating APPL1-AMPK signaling, suggesting that manipulation of APN is a novel therapeutic target for controlling hASC fate. - Highlights: • Adiponectin enhances osteogenic differentiation in human adipose-derived stem cells. • The knock-down of APPL1 block the enhancement of

  16. Effect of short-term exercise training on brain-derived neurotrophic factor signaling in spontaneously hypertensive rats.

    Science.gov (United States)

    Monnier, Alice; Garnier, Philippe; Quirie, Aurore; Pernet, Nicolas; Demougeot, Céline; Marie, Christine; Prigent-Tessier, Anne

    2017-02-01

    Decreased brain-derived neurotrophic factor (BDNF) level has been reported in the hippocampus of hypertensive rats. The present study explored whether brain neurons and/or endothelial cells are targeted by hypertension with respect to BDNF expression and the potential of physical exercise to cope with hypertension. Physical exercise was induced in spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats. The hippocampus of sedentary and exercised rats (n = 6 for each group) were used for western blots to assess proBDNF, mature BDNF (mBDNF), tropomyosin-related kinase B (TrkB), P-TrkB (TrkB phosphorylated at tyrosine 816), synaptophysin, endothelial nitric oxide synthase (eNOS) and eNOS phosphorylated at serine 1177 protein levels. BDNF and proBDNF localization in the hippocampus was studied in WKY rats, SHR and exercised SHR (n = 5 each). mBDNF and proBDNF protein levels were also assessed in hippocampal slices prepared from SHR (n = 10) that were incubated for 24 h with the nitric oxide (NO) donor glyceryl trinitrate. SBP was measured by the tail-cuff method. Exercise modified blood pressure neither in SHR nor WKY. As compared with WKY rats, SHR displayed decreased levels of mBDNF, P-TrkB, synaptophysin, eNOS and eNOS phosphorylated at serine 1177 but no change in proBDNF and TrkB levels. These effects coincided with low BDNF staining in both endothelial cells and neurons. Exercise improved the endothelium-derived NO system and the BDNF pathway in both strains. The NO donor increased mBDNF but decreased proBDNF levels. Our results revealed that endothelial and neuronal BDNF expressions were both impaired in hypertension and that physical exercise improved hippocampal mBDNF levels and signaling through blood pressure-independent mechanisms.

  17. Extracellular Signal-Regulated Kinase Is a Direct Target of the Anti-Inflammatory Compound Amentoflavone Derived from Torreya nucifera

    Directory of Open Access Journals (Sweden)

    Jueun Oh

    2013-01-01

    Full Text Available Amentoflavone is a biflavonoid compound with antioxidant, anticancer, antibacterial, antiviral, anti-inflammatory, and UV-blocking activities that can be isolated from Torreya nucifera, Biophytum sensitivum, and Selaginella tamariscina. In this study, the molecular mechanism underlying amentoflavone’s anti-inflammatory activity was investigated. Amentoflavone dose dependently suppressed the production of nitric oxide (NO and prostaglandin E2 (PGE2 in RAW264.7 cells stimulated with the TLR4 ligand lipopolysaccharide (LPS; derived from Gram-negative bacteria. Amentoflavone suppressed the nuclear translocation of c-Fos, a subunit of activator protein (AP-1, at 60 min after LPS stimulation and inhibited the activity of purified and immunoprecipitated extracellular signal-regulated kinase (ERK, which mediates c-Fos translocation. In agreement with these results, amentoflavone also suppressed the formation of a molecular complex including ERK and c-Fos. Therefore, our data strongly suggest that amentoflavone’s immunopharmacological activities are due to its direct effect on ERK.

  18. Climate Signals on the Regional Scale Derived with a Statistical Method: Relevance of the Driving Model’s Resolution

    Directory of Open Access Journals (Sweden)

    Arne Spekat

    2011-05-01

    Full Text Available When assessing the magnitude of climate signals in a regional scale, a host of optional approaches is feasible. This encompasses the use of regional climate models (RCM, nested into global climate models (GCM for an area of interest as well as employing empirical statistical downscaling methods (ESD. In this context the question is addressed: Is an empirical statistical downscaling method capable of yielding results that are comparable to those by dynamical RCMs? Based on the presented ESD method, the comparison of RCM and ESD results show a high amount of agreement. In addition the empirical statistical downscaling can be applied directly to a GCM or a GCM-RCM cascade. The paper aims at comparing the consequences of employing various CGM-RCM-ESD combinations on the derived future changes of temperature and precipitation. This adds to the insight on the scale dependency of downscaling strategies. Results for one GCM with several scenario runs driving several RCMs with and without subsequent empirical statistical downscaling are presented. It is shown that there are only small differences between using the GCM results directly or as a GCM-RCM-ESD cascade.

  19. Penile vibratory stimulation in the treatment of post-prostatectomy incontinence: a randomized pilot study.

    Science.gov (United States)

    Fode, Mikkel; Sønksen, Jens

    2015-02-01

    To examine penile vibratory stimulation (PVS) in the treatment of post-prostatectomy urinary incontinence (UI). Patients with post-prostatectomy UI were included in a 12-week trial. A 24-hr pad test and a 72-hr voiding diary were collected at baseline. Participants were randomized to receive PVS for the first 6 weeks (group 1) or for the final 6 weeks (group 2) of the study. The primary outcome was the difference in leakage between groups 1 and 2 at 6 weeks as measured by changes in the pad test. The trial was registered at www.clinicaltrials.org (NCT01540656). Data from 31 men were available for analyses. The difference in the change on the pad test between the groups did not reach statistical significance at 6 weeks (P = 0.13) while the change in incontinence episodes between groups approached statistical significance (P = 0.052). However, there was a median reduction of -33 g (P = 0.021) on the pad test and a median reduction in daily incontinence episodes of -1 (P = 0.023) in group 1 at 6 weeks. At 12 weeks, group 2 had a median decrease on the pad test of -8 g (P = 0.10) and no change in incontinence episodes. A pooled analysis showed a decline on the pad test of -13.5 g (P = 0.004) after PVS. Small improvements were seen in subjective symptom scores and 58% stated to be satisfied with PVS. Self-limiting side effects were experienced by 15% of patients. PVS is feasible in the treatment of post-prostatectomy UI. Larger trials are needed to document the clinical efficacy. © 2013 Wiley Periodicals, Inc.

  20. Effect of Axial Force on the Performance of Micromachined Vibratory Rate Gyroscopes

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    Zhengyi Niu

    2010-12-01

    Full Text Available It is reported in the published literature that the resonant frequency of a silicon micromachined gyroscope decreases linearly with increasing temperature. However, when the axial force is considerable, the resonant frequency might increase as the temperature increases. The axial force is mainly induced by thermal stress due to the mismatch between the thermal expansion coefficients of the structure and substrate. In this paper, two types of micromachined suspended vibratory gyroscopes with slanted beams were proposed to evaluate the effect of the axial force. One type was suspended with a clamped-free (C-F beam and the other one was suspended with a clamped-clamped (C-C beam. Their drive modes are the bending of the slanted beam, and their sense modes are the torsion of the slanted beam. The relationships between the resonant frequencies of the two types were developed. The prototypes were packaged by vacuum under 0.1 mbar and an analytical solution for the axial force effect on the resonant frequency was obtained. The temperature dependent performances of the operated mode responses of the micromachined gyroscopes were measured. The experimental values of the temperature coefficients of resonant frequencies (TCF due to axial force were 101.5 ppm/°C for the drive mode and 21.6 ppm/°C for the sense mode. The axial force has a great influence on the modal frequency of the micromachined gyroscopes suspended with a C-C beam, especially for the flexure mode. The quality factors of the operated modes decreased with increasing temperature, and changed drastically when the micromachined gyroscopes worked at higher temperatures.

  1. Effect of axial force on the performance of micromachined vibratory rate gyroscopes.

    Science.gov (United States)

    Hou, Zhanqiang; Xiao, Dingbang; Wu, Xuezhong; Dong, Peitao; Chen, Zhihua; Niu, Zhengyi; Zhang, Xu

    2011-01-01

    It is reported in the published literature that the resonant frequency of a silicon micromachined gyroscope decreases linearly with increasing temperature. However, when the axial force is considerable, the resonant frequency might increase as the temperature increases. The axial force is mainly induced by thermal stress due to the mismatch between the thermal expansion coefficients of the structure and substrate. In this paper, two types of micromachined suspended vibratory gyroscopes with slanted beams were proposed to evaluate the effect of the axial force. One type was suspended with a clamped-free (C-F) beam and the other one was suspended with a clamped-clamped (C-C) beam. Their drive modes are the bending of the slanted beam, and their sense modes are the torsion of the slanted beam. The relationships between the resonant frequencies of the two types were developed. The prototypes were packaged by vacuum under 0.1 mbar and an analytical solution for the axial force effect on the resonant frequency was obtained. The temperature dependent performances of the operated mode responses of the micromachined gyroscopes were measured. The experimental values of the temperature coefficients of resonant frequencies (TCF) due to axial force were 101.5 ppm/°C for the drive mode and 21.6 ppm/°C for the sense mode. The axial force has a great influence on the modal frequency of the micromachined gyroscopes suspended with a C-C beam, especially for the flexure mode. The quality factors of the operated modes decreased with increasing temperature, and changed drastically when the micromachined gyroscopes worked at higher temperatures.

  2. A randomized trial of clitoral vacuum suction versus vibratory stimulation in neurogenic female orgasmic dysfunction.

    Science.gov (United States)

    Alexander, Marcalee; Bashir, Khurram; Alexander, Craig; Marson, Lesley; Rosen, Raymond

    2017-09-09

    To examine safety and efficacy of use of a clitoral vacuum suction device (CVSD) versus vibratory stimulation (V) to treat orgasmic dysfunction in women with MS or SCI. Randomized clinical trial. Two academic medical centers. Thirty-one women including 20 with MS and 11 with SCI. A 12-week trial of the use of a CVSD versus V MAIN OUTCOME MEASURES: Female Sexual Function Inventory (FSFI) and Female Sexual Distress Scale (FSDS). 23 women (18 MS; 5 SCI) completed the study including 13/16 randomized to CVSD and 10/15 randomized to V. There was a statistically significant increase in total FSFI score (p=.011), desire (p=. 009), arousal (p=.009), lubrication (p=.008), orgasm (p=.012), and satisfaction (p=.049) and a significant decrease in distress as measured by FSDS (p=.020) in subjects using the CVSD. In subjects who used V, there was a statistically significant increase in the orgasm subscale of the FSFI (p=.028). Subjects using the CVSD maintained improvements 4 weeks after treatment. CVSD is safe and overall efficacious to treat female neurogenic sexual dysfunction related to MS and SCI. V is also safe and efficacious to female neurogenic orgasmic dysfunction; however, results were limited to the active treatment period. Due to ease of access and cost, clinicians can consider use of V for women with MS or SCI with orgasmic dysfunction. CVSD is recommended for women with multiple sexual dysfunctions or for whom V is ineffective. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  3. Development and evaluation of a vibratory-pneumatic pomegranate arils extractor

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    S. M Nassiri

    2017-05-01

    Full Text Available Introduction Iran is a frontier of pomegranate fruit production in the world (with almost 40 % of the world`s production. However due to traditional processing operations is not ranked as the largest pomegranate exporter. Saveh, Neyriz and Ferdows are the top pomegranate producing cities in Iran. Pomegranate is consumed as a fresh fruit as well as processed product as food additive, paste, syrup, jelly, pectin, jam, beverage, essence, vinegar and concentrate. Aril extraction is the first and essential postharvest operation for pomegranate processing. Arils are mostly extracted manually even in large scales for fresh and processed consumption. This labor intensive operation is rational when aril quality is an important index for consumer. But whenever pomegranate juice is desired, the aril quality has no priority for consumer, and therefore arils can be extracted with less care. Sarig (1985 was the first inventor of a pomegranate aril extractor who employed air jet force to extract the arils. Later, other researchers employed the same method as well as water jet to extract fruit juice and sac. In the present study, fabrication and evaluation of vibratory aril extractor augmented with air system was conducted. Materials and Methods The study was conducted using Rabab cultivar samples which were manually harvested from an orchard in Neyriz town, Fars province. Samples were kept in refrigerator at 5 0C till experimental trials. Initial moisture content of fruit skin, arils and internal fleshes were measured by gravimetric method as 31.7±2.6 %, 61.5±1.8 % and 42.8±1.4 %, respectively and for a whole fruit was measured 45.3±11.5 % (w.b.. For conducting laboratory tests, an aril extraction unit was designed and fabricated. It comprised a steel main frame, a 746 W electric motor, drive mechanism (eccentric and shaft, sample retentive unit, air jet unit, aril tank, and an air compressor-tank assembly. Sample retentive unit was designed in such a

  4. KENeV: A web-application for the automated reconstruction and visualization of the enriched metabolic and signaling super-pathways deriving from genomic experiments

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    Eleftherios Pilalis

    2015-01-01

    In conclusion, KENeV (available online at http://www.grissom.gr/kenev provides an integrative tool, suitable for users with no programming experience, for the functional interpretation, at both the metabolic and signaling level, of differentially expressed gene subsets deriving from genomic experiments.

  5. Implementation of the resonant vibratory feeders control algorithm on Simatic S7-1200 from MATLAB Simulink enviroment

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    Mitrović Radomir B.

    2016-01-01

    Full Text Available Simulink is an important tool for modeling and simulation of process and control algorithms. It's expansion, PLC Coder, enables direct conversion of model subsystem into SCL, structured text code, which is then used by PLC IDE to create function blocks. This shortens developing time of algorithms for PLC controller. Also, this reduces possibility for a coding error. This paper describes Simulink PLC Coder and workflow for developing PID control algorithm for Siemens Simatic S7-1200 PLC. Control object used here is resonant vibratory feeder having electromagnetic drive.

  6. Penile vibratory stimulation in the recovery of urinary continence and erectile function after nerve-sparing radical prostatectomy

    DEFF Research Database (Denmark)

    Fode, Mikkel; Borre, Michael; Ohl, Dana A

    2014-01-01

    OBJECTIVE: To examine the effect of penile vibratory stimulation (PVS) in the preservation and restoration of erectile function and urinary continence in conjunction with nerve-sparing radical prostatectomy (RP). PATIENTS AND METHODS: The present study was conducted between July 2010 and March 2013...... and 12 months after surgery with the IIEF-5 questionnaire and questions regarding urinary bother. Patients using up to one pad daily for security reasons only were considered continent. The study was registered at http://clinicaltrials.gov/ (NCT01067261). RESULTS: Data from 68 patients were available...

  7. Candida albicans induces selective development of macrophages and monocyte derived dendritic cells by a TLR2 dependent signalling.

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    Alberto Yáñez

    Full Text Available As TLRs are expressed by haematopoietic stem and progenitor cells (HSPCs, these receptors may play a role in haematopoiesis in response to pathogens during infection. We have previously demonstrated that in in vitro defined conditions inactivated yeasts and hyphae of Candida albicans induce HSPCs proliferation and differentiation towards the myeloid lineage by a TLR2/MyD88 dependent pathway. In this work, we showed that C. albicans invasive infection with a low virulence strain results in a rapid expansion of HSPCs (identified as LKS cells: Lin(- c-Kit(+ Sca-1(+ IL-7Rα(-, that reach the maximum at day 3 post-infection. This in vivo expansion of LKS cells in TLR2(-/- mice was delayed until day 7 post- infection. Candidiasis was, as expected, accompanied by an increase in granulopoiesis and decreased lymphopoiesis in the bone marrow. These changes were more pronounced in TLR2(-/- mice correlating with their higher fungal burden. Accordingly, emigration of Ly6C(high monocytes and neutrophils to spleen was increased in TLR2(-/- mice, although the increase in macrophages and inflammatory macrophages was completely dependent on TLR2. Similarly, we detected for the first time, in the spleen of C. albicans infected control mice, a newly generated population of dendritic cells that have the phenotype of monocyte derived dendritic cells (moDCs that were not generated in TLR2(-/- infected mice. In addition, C. albicans signalling through TLR2/MyD88 and Dectin-1 promotes in vitro the differentiation of Lin(- cells towards moDCs that secrete TNF-α and are able to kill the microorganism. Therefore, our results indicate that during infection C. albicans can directly stimulate progenitor cells through TLR2 and Dectin-1 to generate newly formed inflammatory macrophages and moDCs that may fulfill an essential role in defense mechanisms against the pathogen.

  8. Brain-derived neurotrophic factor and tyrosine kinase B receptor signalling in post-mortem brain of teenage suicide victims.

    Science.gov (United States)

    Pandey, Ghanshyam N; Ren, Xinguo; Rizavi, Hooriyah S; Conley, Robert R; Roberts, Rosalinda C; Dwivedi, Yogesh

    2008-12-01

    Teenage suicide is a major public health concern, but its neurobiology is not very well understood. Stress and major mental disorders are major risk factors for suicidal behaviour, and it has been shown that brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (TrkB) are not only regulated by stress but are also altered in these illnesses. We therefore examined if BDNF/TrkB signalling is altered in the post-mortem brain of teenage suicide victims. Protein and mRNA expression of BDNF and of TrkB receptors were determined in the prefrontal cortex (PFC), Brodmann's Area 9 (BA 9), and hippocampus obtained from 29 teenage suicide victims and 25 matched normal control subjects. Protein expression was determined using the Western blot technique; mRNA levels by a quantitative RT-PCR technique. The protein expression of BDNF was significantly decreased in the PFC of teenage suicide victims compared with normal control subjects, whereas no change was observed in the hippocampus. Protein expression of TrkB full-length receptors was significantly decreased in both PFC and hippocampus of teenage suicide victims without any significant changes in the truncated form of TrkB receptors. mRNA expression of both BDNF and TrkB was significantly decreased in the PFC and hippocampus of teenage suicide victims compared with normal control subjects. These studies indicate a down-regulation of both BDNF and its receptor TrkB in the PFC and hippocampus of teenage suicide victims, which suggests that stress and altered BDNF may represent a major vulnerability factor in teenage suicidal behaviour.

  9. A new bisphosphonate derivative, CP, induces gastric cancer cell apoptosis via activation of the ERK1/2 signaling pathway.

    Science.gov (United States)

    Wang, Hai-jun; Liu, Yu; Fan, Li-qiao; Han, Cai-li; Jiang, Ye; Cheng, Shu-jie; Li, Yong

    2013-12-01

    To investigate the effects of a new derivative of bisphosphonates, [2-(6-aminopurine-9-yl)-1-hydroxy-phosphine acyl ethyl] phosphonic acid (CP), on human gastric cancer. Human gastric cancer cell lines (SGC-7901, BGC-823, MKN-45, and MKN-28) and human colon carcinoma cell lines (LoVo and HT-29) were tested. Cell growth was determined using the MTT assay. Flow cytometry, Western blot, caspase activity assay and siRNA transfection were used to examine the mechanisms of anticancer action. Female BALB/c nude mice were implanted with SGC-7901 cells. From d6 after inoculation, the animals were injected with CP (200 μg/kg, ip) or vehicle daily for 24 d. CP suppressed the growth of the 6 human cancer cell lines with similar IC50 values (3239 μmol/L). In SGC-7901 cells, CP arrested cell cycle progression at the G2/M phase. The compound activated caspase-9, increased the expression of pro-apoptotic proteins Bax and Bad, decreased the expression of anti-apoptotic protein Bcl-2. Furthermore, the compound selectively activated ERK1/2 without affecting JNK and p38 in SGC-7901 cells. Treatment of SGC-7901 cells with the specific ERK1/2 inhibitor PD98059 or ERK1/2 siRNA hampered CP-mediated apoptosis. In the human gastric cancer xenograft nude mouse model, chronic administration of CP significantly retarded the tumor growth. CP is a broad-spectrum inhibitor of human carcinoma cells in vitro, and it also exerts significant inhibition on gastric cancer cell growth in vivo. CP induces human gastric cancer apoptosis via activation of the ERK1/2 signaling pathway.

  10. Dietary pattern associated with selenoprotein P and MRI-derived body fat volumes, liver signal intensity, and metabolic disorders.

    Science.gov (United States)

    di Giuseppe, Romina; Plachta-Danielzik, Sandra; Koch, Manja; Nöthlings, Ute; Schlesinger, Sabrina; Borggrefe, Jan; Both, Marcus; Müller, Hans-Peter; Kassubek, Jan; Jacobs, Gunnar; Lieb, Wolfgang

    2018-02-14

    The association of complex dietary patterns with circulating selenoprotein P (SELENOP) levels in humans is unknown. In a general population sample, we aimed to identify a dietary pattern explaining inter-individual variation in circulating SELENOP concentrations and to study this pattern in relation to prevalent diabetes, metabolic syndrome (MetS), MRI-determined total volumes of visceral (VAT) and subcutaneous (SAT) abdominal adipose tissue, and liver signal intensity/fatty liver disease. In this cross-sectional study, serum SELENOP levels were measured in 853 individuals. In a subsample of 553 participants, whole-body MRI was performed to assess body fat distribution and liver fat. Dietary intake was assessed by a self-administered food frequency questionnaire and the dietary pattern identified using reduced-rank regression (RRR). Multivariable linear and logistic regressions were used to investigate associations between dietary pattern score and metabolic traits. Characterized by high intake of fruit, vegetables and antioxidant beverages, the RRR-derived dietary pattern displayed inverse associations with VAT, SAT, MetS, and prevalent diabetes in multivariable-adjusted restricted cubic splines. Each unit increase in dietary pattern score was associated with 31% higher SELENOP levels, 12% lower VAT (95% CI: - 19%; - 5%), 13% (95% CI: - 20%; - 6%) lower SAT values and 46% (95% CI: 27%; 60%) and 53% (95% CI: 22%; 72%) lower odds of having MetS or diabetes, respectively. No meaningful relations were observed between the dietary pattern and liver traits. Our observations propose diet-related regulation in SELENOP levels and that the identified dietary pattern is inversely related to VAT, SAT, MetS, and prevalent diabetes.

  11. Activation of Notch1 signaling alleviates dysfunction of bone marrow-derived mesenchymal stem cells induced by cigarette smoke extract

    Directory of Open Access Journals (Sweden)

    Cheng Y

    2017-10-01

    Full Text Available Yi Cheng,* Wen Gu,* Guorui Zhang, Xiaoming Li, Xuejun Guo Department of Respiratory Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China *These authors contributed equally to this work Abstract: Bone marrow-derived mesenchymal stem cells (BM-MSCs are considered attractive therapeutic agents for the treatment of COPD. However, little is known about the impact of Notch on the proliferation, migration, and survival of MSCs in a cigarette smoke (CS microenvironment. Here, we used CS extract to mimic the CS microenvironment in vitro, with the intention to investigate the effect of Notch in regulating proliferation, migration, and survival of BM-MSCs. Rat bone marrow mesenchymal stem cells were infected with lentivirus vector containing the intracellular domain of Notch1 (N1ICD and challenged with CS extract. Cell proliferation was detected by Ki67 staining and expression of cell cycle-related proteins. A transwell assay was used to measure cell migration and the expression of apoptotic proteins was examined. The proliferation of BM-MSCs overexpressing N1ICD significantly increased. Consistently, levels of cyclin D1, p-Rb, and E2F-1 increased in N1ICD overexpressing cells. N1ICD overexpression also increased cell migration compared with the control group. N1ICD overexpression equilibrated the expression of Bax and Bcl-2, and blocked caspase-3 cleavage, contributing to the inhibition of apoptosis. Moreover, blockade of the PI3K/Akt pathway suppressed the aforementioned cytoprotective effects of N1ICD. In conclusion, activation of Notch signaling improved proliferation, migration, and survival of BM-MSCs in a CS microenvironment partly through the PI3K/Akt pathway. Keywords: mesenchymal stem cells, chronic obstructive pulmonary disease, cigarette smoke extract, Notch

  12. Estimating two-point statistics from derivatives of a signal containing noise: Application to auto-correlation functions of turbulent Lagrangian tracks.

    Science.gov (United States)

    Machicoane, N; Huck, P D; Volk, R

    2017-06-01

    This article describes a method for calculating moments and correlation functions of signal derivatives, which were rid of experimental noise without the use of filtering operations. The method is based on the computation of the ensemble-average of different time (or spatial) increments of the signal. The hypotheses are that the noise is white and not correlated with the signal; however, the method is also shown to work with colored noise. The method is first developed, considering white noise, and benchmarked with synthetic trajectories containing noise with variable signal-to-noise ratios. It is then tested on experimental trajectories in the context of Lagrangian tracking of particles in turbulent flows, either containing a short-correlated noise or a colored noise.

  13. Estimating two-point statistics from derivatives of a signal containing noise: Application to auto-correlation functions of turbulent Lagrangian tracks

    Science.gov (United States)

    Machicoane, N.; Huck, P. D.; Volk, R.

    2017-06-01

    This article describes a method for calculating moments and correlation functions of signal derivatives, which were rid of experimental noise without the use of filtering operations. The method is based on the computation of the ensemble-average of different time (or spatial) increments of the signal. The hypotheses are that the noise is white and not correlated with the signal; however, the method is also shown to work with colored noise. The method is first developed, considering white noise, and benchmarked with synthetic trajectories containing noise with variable signal-to-noise ratios. It is then tested on experimental trajectories in the context of Lagrangian tracking of particles in turbulent flows, either containing a short-correlated noise or a colored noise.

  14. Signal informatics as an advanced integrative concept in the framework of medical informatics. New trends demonstrated by examples derived from neuroscience.

    Science.gov (United States)

    Witte, H; Ungureanu, M; Ligges, C; Hemmelmann, D; Wüstenberg, T; Reichenbach, J; Astolfi, L; Babiloni, F; Leistritz, L

    2009-01-01

    The main objective is to show current topics and future trends in the field of medical signal processing which are derived from current research concepts. Signal processing as an integrative concept within the scope of medical informatics is demonstrated. For all examples time-variant multivariate autoregressive models were used. Based on this modeling, the concept of Granger causality in terms of the time-variant Granger causality index and the time-variant partial directed coherence was realized to investigate directed information transfer between different brain regions. Signal informatics encompasses several diverse domains including: processing steps, methodologies, levels and subject fields, and applications. Five trends can be recognized and in order to illustrate these trends, three analysis strategies derived from current neuroscientific studies are presented. These examples comprise high-dimensional fMRI and EEG data. In the first example, the quantification of time-variant-directed information transfer between activated brain regions on the basis of fast-fMRI data is introduced and discussed. The second example deals with the investigation of differences in word processing between dyslexic and normal reading children. Different dynamic neural networks of the directed information transfer are identified on the basis of event-related potentials. The third example shows time-variant cortical connectivity networks derived from a source model. These examples strongly emphasize the integrative nature of signal informatics, encompassing processing steps, methodologies, levels and subject fields, and applications.

  15. Use Videostrobokymography to Quantitatively Analyze the Vibratory Characteristics Before and After Conservative Medical Treatment of Vocal Fold Leukoplakia.

    Science.gov (United States)

    Gao, Xiao-Wei; Huang, Yong-Wang; Liu, Li-Yan; Ouyang, Jie

    2016-03-01

    To quantitatively analyze the vibratory characteristics of vocal folds before and after conservative treatments to evaluate the outcomes of conservative treatments for vocal fold leukoplakia using videostrobokymography (VSK). This is a prospective study. Twenty patients and 20 controls were enrolled into the study. All patients received conservative treatments for 3 weeks and received VSK examination before and 3 weeks after the treatments. All controls only received VSK examination once. Vocal fold lengths of 25%, 50%, and 75% were chosen as the line-scan positions to evaluate the vocal fold vibration. Open quotient (OQ) and asymmetry index (AI) were obtained using VSK. Significant improvements in the main symptoms including voice hoarseness were found. Videostroboscopic findings showed that the white lesions on the vocal folds almost completely disappeared in all patients, and the vocal fold flexibility returned to normal. All OQs and AIs at each line-scan position in patients before the treatments were larger than those in controls (P  0.017). VSK could quantitatively evaluate the vibratory characteristics of vocal folds before and after the treatments, and conservative treatment could improve VSK measurements to normal control values, suggesting that VSK is a tool to assess the outcomes of the conservative treatments for vocal fold leukoplakia. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  16. Signal Factors Secreted by 2D and Spheroid Mesenchymal Stem Cells and by Cocultures of Mesenchymal Stem Cells Derived Microvesicles and Retinal Photoreceptor Neurons.

    Science.gov (United States)

    Xie, Lili; Mao, Mao; Zhou, Liang; Zhang, Lusi; Jiang, Bing

    2017-01-01

    We aim to identify levels of signal factors secreted by MSCs cultured in 2D monolayers (2D-MSCs), spheroids (spheroids MSCs), and cocultures of microvesicles (MVs) derived from 2D-MSCs or spheroid MSCs and retinal photoreceptor neurons. We seeded 2D-MSCs, spheroid MSCs, and cells derived from spheroids MSCs at equal numbers. MVs isolated from all 3 culture conditions were incubated with 661W cells. Levels of 51 signal factors in conditioned medium from those cultured conditions were quantified with bead-based assay. We found that IL-8, IL-6, and GROα were the top three most abundant signal factors. Moreover, compared to 2D-MSCs, levels of 11 cytokines and IL-2Rα were significantly increased in conditioned medium from spheroid MSCs. Finally, to test if enhanced expression of these factors reflects altered immunomodulating activities, we assessed the effect of 2D-MSC-MVs and 3D-MSC-MVs on CD14+ cell chemoattraction. Compared to 2D-MSC-MVs, 3D-MSC-MVs significantly decreased the chemotactic index of CD14+ cells. Our results suggest that spheroid culture conditions improve the ability of MSCs to selectively secrete signal factors. Moreover, 3D-MSC-MVs also possessed an enhanced capability to promote signal factors secretion compared to 2D-MSC-MVs and may possess enhanced immunomodulating activities and might be a better regenerative therapy for retinal degenerative diseases.

  17. Molecular modelling of berberine derivatives as inhibitors of human smoothened receptor and hedgehog signalling pathway using a newly developed algorithm on anti-cancer drugs.

    Science.gov (United States)

    Kaboli, Parham Jabbarzadeh; Bazrafkan, Mohammad; Ismail, Patimah; Ling, King-Hwa

    2017-09-29

    Protoberberine isoquinoline alkaloids are found in many plant species. They consist of a diverse class of secondary metabolites with many pharmacologically active members, such as different derivatives of berberine already patented. In the development of approximately 20-25% of all cancers, altered hedgehog (Hh) signalling is involved where the smoothened (Smo) transmembrane receptor triggers Hh signalling pathway towards Gli1 gene expression. The current study aimed to model and verify the anti-Smo activity of berberine and its derivatives using a novel automated script. Based on the patented inventions filed on ADMET modelling until 2016, which also predicts ADMET parameters and binding efficiency indices for all molecules, a script was developed to run automated molecular docking for a large number of small molecules. Berberine was found to interact with Lys395 of Smo receptor via hydrogen bonding and cation-π interactions. In addition, π-π interactions between berberine aromatic rings and two aromatic residues in the Smo transmembrane domain, Tyr394 and Phe484, were noted. Binding efficiency indices using an in-silico approach to plot the Smo-specific binding potency of each ligand was performed. The mRNA level of Gli1 was studied as the outcome of Hh signalling pathway to show the effect of berberine on hedgehog signalling. This study predicted the role of berberine as an inhibitor of Smo receptor, suggesting its effectiveness in hedgehog signalling during cancer treatment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Improved voltammetric method for simultaneous determination of Pt and Rh using second derivative signal transformation - application to environmental samples.

    Science.gov (United States)

    Monteiro, Carlos E; Cobelo-Garcia, Antonio; Caetano, Miguel; Correia Dos Santos, Margarida M

    2017-12-01

    The determination of Platinum-group elements (PGE) in relevant environmental matrices is a challenging task. Sensitive and accurate analytical procedures for simultaneous determination of Pt and Rh are still needed. In this study, we report for the first time on the use of second derivative signal transformation to the ultra-trace simultaneous determination of Pt and Rh by Adsorptive Cathodic Stripping Voltammetry (AdCSV). With that step, the ill-defined peaks typically observed in the original voltammograms are transformed into well-shaped peaks, resulting in accurate detection. The experimental conditions were investigated and optimised: a suitable electrolyte for both elements, with less reagents consumption, (0.25M H2SO4, 0.05M HCl, 0.01M FA and 0.5mM HZ), deposition time (td) and deposition potential (Ed). For td = 120s and Ed = -0.75V, linear relationships r > 0.999 were obtained in the concentration range up to 5.8ngL-1 (27 pM) for Pt and up to 3.4ngL-1 (34 pM) for Rh. Limits of detection were 0.2ngL-1 for Pt and 0.08ngL-1 for Rh. Lower values can be achieved by increasing the deposition time. Limits of quantification, LOQ, calculated as 3 times LOD, were 0.5ngL-1 for Pt and 0.2ngL-1 for Rh. The sensitivity of Pt was affected by elevated Zn concentrations, whereas a minor effect was observed for Rh. However, Pt and Rh determinations were not influenced using the standard addition method. Precision as intermediate precision and expressed as relative standard deviation, based on Pt and Rh spiked solutions and digested road dust CRM BCR-723 was 17% and 20% for Pt and Rh, respectively. Recoveries of CRM were around 90% for both elements. The method was successfully applied in the simultaneous determination of Pt and Rh in sediments from Tagus estuary and, for the first time, dissolved Rh was determined in water samples of a waste water treatment plant. Application of this technique in a multidisciplinary approach will be a relevant contribution to the current

  19. Real-time estimation of the ECG-derived respiration (EDR) signal using a new algorithm for baseline wander noise removal.

    Science.gov (United States)

    Arunachalam, Shivaram P; Brown, Lewis F

    2009-01-01

    Numerous methods have been reported for deriving respiratory information such as respiratory rate from the electrocardiogram (ECG). In this paper the authors present a real-time algorithm for estimation and removal of baseline wander (BW) noise and obtaining the ECG-derived respiration (EDR) signal for estimation of a patient's respiratory rate. This algorithm utilizes a real-time "T-P knot" baseline wander removal technique which is based on the repetitive backward subtraction of the estimated baseline from the ECG signal. The estimated baseline is interpolated from the ECG signal at midpoints between each detected R-wave. As each segment of the estimated baseline signal is subtracted from the ECG, a "flattened" ECG signal is produced for which the amplitude of each R-wave is analyzed. The respiration signal is estimated from the amplitude modulation of R-waves caused by breathing. Testing of the algorithm was conducted in a pseudo real-time environment using MATLAB(TM), and test results are presented for simultaneously recorded ECG and respiration recordings from the PhysioNet/PhysioBank Fantasia database. Test data from patients were chosen with particularly large baseline wander components to ensure the reliability of the algorithm under adverse ECG recording conditions. The algorithm yielded EDR signals with a respiration rate of 4.4 breaths/min. for Fantasia patient record f2y10 and 10.1 breaths/min. for Fantasia patient record f2y06. These were in good agreement with the simultaneously recorded respiration data provided in the Fantasia database thus confirming the efficacy of the algorithm.

  20. Targeted Regulation of PI3K/Akt/mTOR/NF-κB Signaling by Indole Compounds and their Derivatives: Mechanistic Details and Biological Implications for Cancer Therapy

    Science.gov (United States)

    Ahmad, Aamir; Biersack, Bernhard; Li, Yiwei; Kong, Dejuan; Bao, Bin; Schobert, Rainer; Padhye, Subhash B.; Sarkar, Fazlul H.

    2014-01-01

    Indole compounds, found in cruciferous vegetables, are potent anti-cancer agents. Studies with indole-3-carbinol (I3C) and its dimeric product, 3,3’-diindolylmethane (DIM) suggest that these compounds have the ability to deregulate multiple cellular signaling pathways, including PI3K/Akt/mTOR signaling pathway. These natural compounds are also effective modulators of downstream transcription factor NF-κB signaling which might help explain their ability to inhibit invasion and angiogenesis, and the reversal of epithelial-to-mesenchymal transition (EMT) phenotype and drug resistance. Signaling through PI3K/Akt/mTOR and NF-κB pathway is increasingly being realized to play important role in EMT through the regulation of novel miRNAs which further validates the importance of this signaling network and its regulations by indole compounds. Here we will review the available literature on the modulation of PI3K/Akt/mTOR/NF-κB signaling by both parental I3C and DIM, as well as their analogs/derivatives, in an attempt to catalog their anticancer activity. PMID:23272910

  1. Time-dependent evolution of functional vs. remodeling signaling in induced pluripotent stem cell-derived cardiomyocytes and induced maturation with biomechanical stimulation.

    Science.gov (United States)

    Jung, Gwanghyun; Fajardo, Giovanni; Ribeiro, Alexandre J S; Kooiker, Kristina Bezold; Coronado, Michael; Zhao, Mingming; Hu, Dong-Qing; Reddy, Sushma; Kodo, Kazuki; Sriram, Krishna; Insel, Paul A; Wu, Joseph C; Pruitt, Beth L; Bernstein, Daniel

    2016-04-01

    Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a powerful platform for uncovering disease mechanisms and assessing drugs for efficacy/toxicity. However, the accuracy with which hiPSC-CMs recapitulate the contractile and remodeling signaling of adult cardiomyocytes is not fully known. We used β-adrenergic receptor (β-AR) signaling as a prototype to determine the evolution of signaling component expression and function during hiPSC-CM maturation. In "early" hiPSC-CMs (less than or equal to d 30), β2-ARs are a primary source of cAMP/PKA signaling. With longer culture, β1-AR signaling increases: from 0% of cAMP generation at d 30 to 56.8 ± 6.6% by d 60. PKA signaling shows a similar increase: 15.7 ± 5.2% (d 30), 49.8 ± 0.5% (d 60), and 71.0 ± 6.1% (d 90). cAMP generation increases 9-fold from d 30 to 60, with enhanced coupling to remodeling pathways (e.g., Akt and Ca(2+)/calmodulin-dependent protein kinase type II) and development of caveolin-mediated signaling compartmentalization. By contrast, cardiotoxicity induced by chronic β-AR stimulation, a major component of heart failure, develops much later: 5% cell death at d 30vs 55% at d 90. Moreover, β-AR maturation can be accelerated by biomechanical stimulation. The differential maturation of β-AR functionalvs remodeling signaling in hiPSC-CMs has important implications for their use in disease modeling and drug testing. We propose that assessment of signaling be added to the indices of phenotypic maturation of hiPSC-CMs.-Jung, G., Fajardo, G., Ribeiro, A. J. S., Kooiker, K. B., Coronado, M., Zhao, M., Hu, D.-Q., Reddy, S., Kodo, K., Sriram, K., Insel, P. A., Wu, J. C., Pruitt, B. L., Bernstein, D. Time-dependent evolution of functionalvs remodeling signaling in induced pluripotent stem cell-derived cardiomyocytes and induced maturation with biomechanical stimulation. © FASEB.

  2. Use of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes (hiPSC-CMs) to Monitor Compound Effects on Cardiac Myocyte Signaling Pathways.

    Science.gov (United States)

    Guo, Liang; Eldridge, Sandy; Furniss, Mike; Mussio, Jodie; Davis, Myrtle

    2015-09-01

    There is a need to develop mechanism-based assays to better inform risk of cardiotoxicity. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are rapidly gaining acceptance as a biologically relevant in vitro model for use in drug discovery and cardiotoxicity screens. Utilization of hiPSC-CMs for mechanistic investigations would benefit from confirmation of the expression and activity of cellular pathways that are known to regulate cardiac myocyte viability and function. This unit describes an approach to demonstrate the presence and function of signaling pathways in hiPSC-CMs and the effects of treatments on these pathways. We present a workflow that employs protocols to demonstrate protein expression and functional integrity of signaling pathway(s) of interest and to characterize biological consequences of signaling modulation. These protocols utilize a unique combination of structural, functional, and biochemical endpoints to interrogate compound effects on cardiomyocytes. Copyright © 2015 John Wiley & Sons, Inc.

  3. OPTIMIZATION OF MANUFACTURING TEHNOLOGY FOR “ECCENTRIC MASS” COMPONENT OF A NEW TYPE OF VIBRATORY COMPACTOR USING NX 7.5 SOFTWARE

    Directory of Open Access Journals (Sweden)

    Eftimie Dorin

    2013-11-01

    Full Text Available The paper presents the technological optimization process of the eccentric mass component using the NX 7.5 software. The new design of the vibratory compactor with variable amplitudes was modeled 3D. The manufacturing technology presents graphical aspects of operations during mechanical processing.

  4. A New Synthetic Ursolic Acid Derivative IUA with Anti-Tumor Efficacy Against Osteosarcoma Cells via Inhibition of JNK Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Jian Chen

    2014-08-01

    Full Text Available Background: Osteosarcoma is the most common primary malignant bone tumor in children and adolescents and is characterized by frequent metastasis and resistance to chemotherapy. Because osteosarcoma cells are not highly susceptible to current chemotherapy drugs, new alternative strategies for the treatment of osteosarcoma are needed. This study was undertaken to investigate the inhibitory effects of a new synthetic ursolic acid derivative IUA on osteosarcoma cells and to explore its molecular mechanism. We also intended to identify new therapeutic candidates. Methods: We used MTT assay to assess the effect of IUA on the proliferation of osteosarcoma cells. Western-blot analysis was performed to examine downstream molecular events. The Annexin V method was used to evaluate the effect of IUA on apoptosis of osteosarcoma cells. The cell cycle of IUA-treated cells was examined by flow cytometry, and the in vivo effects of this new ursolic acid derivative were evaluated in a mouse osteosarcoma model. Results: The results showed that the new synthetic ursolic acid derivative IUA significantly decreased viability of osteosarcoma cells in vitro and in vivo. It could also induce apoptosis and G1 phase arrest of osteosarcoma cells. The JNK signaling pathway was significantly inhibited, and cleaved caspase-3 protein was increased. Conclusion: We concluded that the new synthetic ursolic acid derivative IUA induces proliferation inhibition and apoptosis of osteosarcoma cells in vitro and in vivo via the down-regulation of the JNK signaling pathway, making it a promising agent for the prevention and treatment of human osteosarcoma.

  5. An Isoxazole Chalcone Derivative Enhances Melanogenesis in B16 Melanoma Cells via the Akt/GSK3β/β-Catenin Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Li Yin

    2017-11-01

    Full Text Available Plants or plant-derived products have been routinely used in several traditional medicine systems for vitiligo treatment. It is well-known that melanogenesis can be promoted by certain flavonoid compounds isolated from the traditional Uyghur medicinal plant, Kaliziri. Therefore, Chalcones, one class of flavonoid compounds, has become an interesting target for the development of anti-vitiligo agents. A series of novel isoxazole chalcone derivatives have been designed, synthesized, and evaluated for biological activities by our group. Among them, derivative 1-(4-((3-phenylisoxazol-5-ylmethoxyphenyl-3-phenylprop-2-en-1-one (PMPP was identified as a potent tyrosinase activator with better activity and lower toxicity than the positive control 8-methoxypsoralen (8-MOP in this study. Further investigations revealed that Akt and GSK3β were the signaling pathways involved in the hyperpigmentation of PMPP. Overall, these studies may provide a convenient and novel approach for the further development of anti-vitiligo agents.

  6. A new goniothalamin N-acylated aza-derivative strongly downregulates mediators of signaling transduction associated with pancreatic cancer aggressiveness.

    Science.gov (United States)

    Barcelos, Rosimeire Coura; Pelizzaro-Rocha, Karin Juliane; Pastre, Julio Cezar; Dias, Marina Pereira; Ferreira-Halder, Carmen Veríssima; Pilli, Ronaldo Aloise

    2014-11-24

    In this study, a novel concise series of molecules based on the structure of goniothalamin (1) was synthesized and evaluated against a highly metastatic human pancreatic cancer cell line (Panc-1). Among them, derivative 8 displayed a low IC50 value (2.7 μM) and its concentration for decreasing colony formation was 20-fold lower than goniothalamin (1). Both compounds reduced the levels of the receptor tyrosine kinase (AXL) and cyclin D1 which are known to be overexpressed in pancreatic cancer cells. Importantly, despite the fact that goniothalamin (1) and derivative 8 caused pancreatic cancer cell cycle arrest and cell death, only derivative 8 was able to downregulate pro-survival and proliferation pathways mediated by mitogen activated protein kinase ERK1/2. Another interesting finding was that Panc-1 cells treated with derivative 8 displayed a strong decrease in the transcription factor (c-Myc), hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) protein levels. Notably, the molecular effects caused by derivative 8 might not be related to ROS generation, since no significant production of ROS was observed in low concentrations of this compound (from 1.5 up to 3 μM). Therefore, the downregulation of important mediators of pancreatic cancer aggressiveness by derivative 8 reveals its great potential for the development of new chemotherapeutic agents for pancreatic cancer treatment. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  7. NOTCH Signaling Is Essential for Maturation, Self-Renewal, and Tri-Differentiation of In Vitro Derived Human Neural Stem Cells.

    Science.gov (United States)

    Venkatesh, Katari; Reddy, L Vinod Kumar; Abbas, Salar; Mullick, Madhubanti; Moghal, Erfath Thanjeem Begum; Balakrishna, Janardhana Papayya; Sen, Dwaipayan

    2017-10-16

    Although neural stem cells (NSCs) have potential applications in treating neurological disorders, much still needs to be understood about the differentiation biology for their successful clinical translation. In this study, we aimed at deriving NSCs from human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) and explored the role of Notch signaling in the differentiation process. The hUCB-MSCs were characterized as per guidelines of the International Society of Cellular Therapy. NSCs were successfully generated from hUCB-MSCs by using epidermal and fibroblast growth factors under serum-free conditions. The expression of NSC markers (Nestin and Musashi-1) in the neurospheres generated from hUCB-MSCs in the presence or absence of N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT; Notch inhibitor) was immuno-phenotypically characterized by using immunofluorescence. DAPT showed significant (*p process is Notch dependent. These data were further correlated with formation of a reduced average number of neurospheres derived from hUCB-MSCs (2 colonies vs. 11 colonies/field of view) in the presence of DAPT compared with the control (without DAPT). The expression of Notch target genes in NSC cultures (Notch intracellular domain [NICD], HES1, and HES5) was also significantly downregulated after DAPT treatment. In the presence of DAPT, the markers for neuronal (MAP2, NEFH); and glial (GFAP, GLUL, and MBP) lineages were significantly downregulated as seen via immunofluorescence and quantitative polymerase chain reaction, indicating the role of Notch in the tri-differentiation mechanism of NSCs as well. In addition, Notch signaling inhibition induced higher cell death during the lineage commitment of NSCs as measured 3 days (16.9% vs. 8.9%) and 6 days (42.9% vs. 20.8%) postinduction. These results suggest that the efficient derivation of NSCs and their subsequent lineage commitment from hUCB-MSCs requires the Notch signaling pathway.

  8. Engineering applications and analysis of vibratory motion fourth order fluid film over the time dependent heated flat plate

    Science.gov (United States)

    Mohmand, Muhammad Ismail; Mamat, Mustafa Bin; Shah, Qayyum

    2017-07-01

    This article deals with the time dependent analysis of thermally conducting and Magneto-hydrodynamic (MHD) liquid film flow of a fourth order fluid past a vertical and vibratory plate. In this article have been developed for higher order complex nature fluids. The governing-equations have been modeled in the terms of nonlinear partial differential equations with the help of physical boundary circumstances. Two different analytical approaches i.e. Adomian decomposition method (ADM) and the optimal homotopy asymptotic method (OHAM), have been used for discoveryof the series clarification of the problems. Solutions obtained via two diversemethods have been compared using the graphs, tables and found an excellent contract. Variants of the embedded flow parameters in the solution have been analysed through the graphical diagrams.

  9. Low-frequency vibratory exercise reduces the risk of bone fracture more than walking: a randomized controlled trial.

    Science.gov (United States)

    Gusi, Narcís; Raimundo, Armando; Leal, Alejo

    2006-11-30

    Whole-body vibration (WBV) is a new type of exercise that has been increasingly tested for the ability to prevent bone fractures and osteoporosis in frail people. There are two currently marketed vibrating plates: a) the whole plate oscillates up and down; b) reciprocating vertical displacements on the left and right side of a fulcrum, increasing the lateral accelerations. A few studies have shown recently the effectiveness of the up-and-down plate for increasing Bone Mineral Density (BMD) and balance; but the effectiveness of the reciprocating plate technique remains mainly unknown. The aim was to compare the effects of WBV using a reciprocating platform at frequencies lower than 20 Hz and a walking-based exercise programme on BMD and balance in post-menopausal women. Twenty-eight physically untrained post-menopausal women were assigned at random to a WBV group or a Walking group. Both experimental programmes consisted of 3 sessions per week for 8 months. Each vibratory session included 6 bouts of 1 min (12.6 Hz in frequency and 3 cm in amplitude with 60 degrees of knee flexion) with 1 min rest between bouts. Each walking session was 55 minutes of walking and 5 minutes of stretching. Hip and lumbar BMD (g.cm-2) were measured using dual-energy X-ray absorptiometry and balance was assessed by the blind flamingo test. ANOVA for repeated measurements was adjusted by baseline data, weight and age. After 8 months, BMD at the femoral neck in the WBV group was increased by 4.3% (P = 0.011) compared to the Walking group. In contrast, the BMD at the lumbar spine was unaltered in both groups. Balance was improved in the WBV group (29%) but not in the Walking group. The 8-month course of vibratory exercise using a reciprocating plate is feasible and is more effective than walking to improve two major determinants of bone fractures: hip BMD and balance.

  10. Regulation of PGE2 signaling pathways and TNF-alpha signaling pathways on the function of bone marrow-derived dendritic cells and the effects of CP-25.

    Science.gov (United States)

    Li, Ying; Sheng, Kangliang; Chen, Jingyu; Wu, Yujing; Zhang, Feng; Chang, Yan; Wu, Huaxun; Fu, Jingjing; Zhang, Lingling; Wei, Wei

    2015-12-15

    This study was to investigate PGE2 and TNF-alpha signaling pathway involving in the maturation and activation of bone marrow dendritic cells (DCs) and the effect of CP-25. Bone marrow DCs were isolated and stimulated by PGE2 and TNF-alpha respectively. The markers of maturation and activation expressed on DCs, such as CD40, CD80, CD83, CD86, MHC-II, and the ability of antigen uptake of DCs were analyzed by flow cytometry. The proliferation of T cells co-cultured with DCs, the signaling pathways of PGE2-EP4-cAMP and TNF-alpha-TRADD-TRAF2-NF-κB in DCs were analyzed. The results showed that both PGE2 and TNF-alpha up-regulated the expressions of CD40, CD80, CD83, CD86, and MHC-II, decreased the antigen uptake of DCs, and DCs stimulated by PGE2 or TNF-alpha could increase T cell proliferation. CP-25 (10(-5), 10(-6), and 10(-7)mol/l) decreased significantly the expressions of CD40, CD80, CD83, CD86 and MHC-II, increased the antigen uptake of DCs, and suppressed T cell proliferation induced by DCs. PGE2 increased the expressions of EP4, NF-κB and down-regulated cAMP level of DCs. TNF-alpha could also up-regulate TNFR1, TRADD, TRAF2, and NF-κB expression of DCs. CP-25 (10(-5), 10(-6), and 10(-7)mol/l) decreased the expressions of EP4 and NF-κB, increased cAMP level in DCs stimulated by PGE2. CP-25 (10(-5), 10(-6), and 10(-7)mol/l) also could down-regulate significantly TNFR1, TRADD, TRAF2, and NF-κB expression in DCs stimulated by TNF-alpha. These results demonstrate that PGE2 and TNF-alpha could enhance DCs functions by mediating PGE2-EP4-cAMP pathway, TNF-alpha-TNFR1-TRADD-TRAF2-NF-κB pathway respectively. CP-25 might inhibit the function of DCs through regulating PGE2-EP4-cAMP and TNF-alpha-TNFR1-TRADD-TRAF2-NF-κB pathways. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Comparing signal to noise ratios of amplitude modulation following responses from four EEG derivations in awake normally hearing adults.

    NARCIS (Netherlands)

    Reijden, C.S. van der; Mens, L.H.M.; Snik, A.F.M.

    2001-01-01

    Amplitude modulation following responses (AMFR) or steady-state evoked potentials (SSEPs) can be used for the objective and frequency-specific estimation of hearing thresholds in awake and sleeping subjects. To be useful as a clinical tool, a high signal to noise ratio (SNR) is required for a

  12. Melanoma cell-derived exosomes promote epithelial-mesenchymal transition in primary melanocytes through paracrine/autocrine signaling in the tumor microenvironment

    Science.gov (United States)

    Xiao, Deyi; Barry, Samantha; Kmetz, Daniel; Egger, Michael; Pan, Jianmin; Rai, Shesh N; Qu, Jifu; McMasters, Kelly M.; Hao, Hongying

    2016-01-01

    The tumor microenvironment is abundant with exosomes that are secreted by the cancer cells themselves. Exosomes are nanosized, organelle-like membranous structures that are increasingly being recognized as major contributors in the progression of malignant neoplasms. A critical element in melanoma progression is its propensity to metastasize, but little is known about how melanoma cell-derived exosomes modulate the microenvironment to optimize conditions for tumor progression and metastasis. Here, we provide evidence that melanoma cell-derived exosomes promote phenotype switching in primary melanocytes through paracrine/autocrine signaling. We found that the mitogen-activated protein kinase (MAPK) signaling pathway was activated during the exosome-mediated epithelial-to-mesenchymal transition (EMT)-resembling process, which promotes metastasis. Let-7i, an miRNA modulator of EMT, was also involved in this process. We further defined two other miRNA modulators of EMT (miR-191 and let-7a) in serum exosomes for differentiating stage I melanoma patients from non-melanoma subjects. These results provide the first strong molecular evidence that melanoma cell-derived exosomes promote the EMT-resembling process in the tumor microenvironment. Thus, novel strategies targeting EMT and modulating the tumor microenvironment may emerge as important approaches for the treatment of metastatic melanoma. PMID:27063098

  13. Melanoma cell-derived exosomes promote epithelial-mesenchymal transition in primary melanocytes through paracrine/autocrine signaling in the tumor microenvironment.

    Science.gov (United States)

    Xiao, Deyi; Barry, Samantha; Kmetz, Daniel; Egger, Michael; Pan, Jianmin; Rai, Shesh N; Qu, Jifu; McMasters, Kelly M; Hao, Hongying

    2016-07-01

    The tumor microenvironment is abundant with exosomes that are secreted by the cancer cells themselves. Exosomes are nanosized, organelle-like membranous structures that are increasingly being recognized as major contributors in the progression of malignant neoplasms. A critical element in melanoma progression is its propensity to metastasize, but little is known about how melanoma cell-derived exosomes modulate the microenvironment to optimize conditions for tumor progression and metastasis. Here, we provide evidence that melanoma cell-derived exosomes promote phenotype switching in primary melanocytes through paracrine/autocrine signaling. We found that the mitogen-activated protein kinase (MAPK) signaling pathway was activated during the exosome-mediated epithelial-to-mesenchymal transition (EMT)-resembling process, which promotes metastasis. Let-7i, an miRNA modulator of EMT, was also involved in this process. We further defined two other miRNA modulators of EMT (miR-191 and let-7a) in serum exosomes for differentiating stage I melanoma patients from non-melanoma subjects. These results provide the first strong molecular evidence that melanoma cell-derived exosomes promote the EMT-resembling process in the tumor microenvironment. Thus, novel strategies targeting EMT and modulating the tumor microenvironment may emerge as important approaches for the treatment of metastatic melanoma. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Alk3 mediated Bmp signaling controls the contribution of epicardially derived cells to the tissues of the atrioventricular junction

    NARCIS (Netherlands)

    Lockhart, Marie M.; Boukens, Bastiaan J. D.; Phelps, Aimee L.; Brown, Christina-Lin M.; Toomer, Katelynn A.; Burns, Tara A.; Mukherjee, Rupak D.; Norris, Russell A.; Trusk, Thomas C.; van den Hoff, Maurice J. B.; Wessels, Andy

    2014-01-01

    Recent studies using mouse models for cell fate tracing of epicardial derived cells (EPDCs) have demonstrated that at the atrioventricular (AV) junction EPDCs contribute to the mesenchyme of the AV sulcus, the annulus fibrosus, and the parietal leaflets of the AV valves. There is little insight,

  15. Physiological noise correction using ECG-derived respiratory signals for enhanced mapping of spontaneous neuronal activity with simultaneous EEG-fMRI.

    Science.gov (United States)

    Abreu, Rodolfo; Nunes, Sandro; Leal, Alberto; Figueiredo, Patrícia

    2017-07-01

    The study of spontaneous brain activity based on BOLD-fMRI may be seriously compromised by the presence of signal fluctuations of non-neuronal origin, most prominently due to cardiac and respiratory mechanisms. Methods used for modeling and correction of the so-called physiological noise usually rely on the concurrent measurement of cardiac and respiratory signals. In simultaneous EEG-fMRI recordings, which are primarily aimed at the study of spontaneous brain activity, the electrocardiogram (ECG) is typically measured as part of the EEG setup but respiratory data are not generally available. Here, we propose to use the ECG-derived respiratory (EDR) signal estimated by Empirical Mode Decomposition (EMD) as a surrogate of the respiratory signal, for retrospective physiological noise correction of typical simultaneous EEG-fMRI data. A physiological noise model based on these physiological signals (P-PNM) complemented with fMRI-derived noise regressors was generated, and evaluated, for 17 simultaneous EEG-fMRI datasets acquired from a group of seven epilepsy patients imaged at 3T. The respiratory components of P-PNM were found to explain BOLD variance significantly in addition to the cardiac components, suggesting that the EDR signal was successfully extracted from the ECG, and P-PNM outperformed an image-based model (I-PNM) in terms of total BOLD variance explained. Further, the impact of the correction using P-PNM on fMRI mapping of patient-specific epileptic networks and the resting-state default mode network (DMN) was assessed in terms of sensitivity and specificity and, when compared with an ICA-based procedure and a standard pre-processing pipeline, P-PNM achieved the best performance. Overall, our results support the feasibility and utility of extracting physiological noise models of the BOLD signal resorting to ECG data exclusively, with substantial impact on the simultaneous EEG-fMRI mapping of resting-state networks, and, most importantly, epileptic networks

  16. Role of human amnion-derived mesenchymal stem cells in promoting osteogenic differentiation by influencing p38 MAPK signaling in lipopolysaccharide -induced human bone marrow mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yuli; Wu, Hongxia; Shen, Ming; Ding, Siyang; Miao, Jing; Chen, Ning, E-mail: 2927410849@qq.com

    2017-01-01

    Periodontitis is a chronic inflammatory disease induced by bacterial pathogens, which not only affect connective tissue attachments but also cause alveolar bone loss. In this study, we investigated the anti-inflammatory effects of Human amnion-derived mesenchymal stem cells (HAMSCs) on human bone marrow mesenchymal stem cells (HBMSCs) under lipopolysaccharide (LPS)-induced inflammatory conditions. Proliferation levels were measured by flow cytometry and immunofluorescence staining of 5-ethynyl-2′-deoxyuridine (EdU). Osteoblastic differentiation and mineralization were investigated using chromogenic alkaline phosphatase activity (ALP) activity substrate assays, Alizarin red S staining, and RT-PCR analysis of HBMSCs osteogenic marker expression. Oxidative stress induced by LPS was investigated by assaying reactive oxygen species (ROS) level and superoxide dismutase (SOD) activity. Here, we demonstrated that HAMSCs increased the proliferation, osteoblastic differentiation, and SOD activity of LPS-induced HBMSCs, and down-regulated the ROS level. Moreover, our results suggested that the activation of p38 MAPK signal transduction pathway is essential for reversing the LPS-induced bone-destructive processes. SB203580, a selective inhibitor of p38 MAPK signaling, significantly suppressed the anti-inflammatory effects in HAMSCs. In conclusion, HAMSCs show a strong potential in treating inflammation-induced bone loss by influencing p38 MAPK signaling. - Highlights: • LPS inhibites osteogenic differentiation in HBMSCs via suppression of p38 MAPK signaling pathway. • HAMSCs promote LPS-induced HBMSCs osteogenic differentiation through p38 MAPK signaling pathway. • HAMSCs reverse LPS-induced oxidative stress in LPS-induced HBMSCs through p38 MAPK signaling pathway.

  17. Perception of root-derived peptides by shoot LRR-RKs mediates systemic N-demand signaling.

    Science.gov (United States)

    Tabata, Ryo; Sumida, Kumiko; Yoshii, Tomoaki; Ohyama, Kentaro; Shinohara, Hidefumi; Matsubayashi, Yoshikatsu

    2014-10-17

    Nitrogen (N) is a critical nutrient for plants but is often distributed unevenly in the soil. Plants therefore have evolved a systemic mechanism by which N starvation on one side of the root system leads to a compensatory and increased nitrate uptake on the other side. Here, we study the molecular systems that support perception of N and the long-distance signaling needed to alter root development. Rootlets starved of N secrete small peptides that are translocated to the shoot and received by two leucine-rich repeat receptor kinases (LRR-RKs). Arabidopsis plants deficient in this pathway show growth retardation accompanied with N-deficiency symptoms. Thus, signaling from the root to the shoot helps the plant adapt to fluctuations in local N availability. Copyright © 2014, American Association for the Advancement of Science.

  18. Simple locking of infrared and ultraviolet diode lasers to a visible laser using a LabVIEW proportional-integral-derivative controller on a Fabry-Perot signal.

    Science.gov (United States)

    Kwolek, J M; Wells, J E; Goodman, D S; Smith, W W

    2016-05-01

    Simultaneous laser locking of infrared (IR) and ultraviolet lasers to a visible stabilized reference laser is demonstrated via a Fabry-Perot (FP) cavity. LabVIEW is used to analyze the input, and an internal proportional-integral-derivative algorithm converts the FP signal to an analog locking feedback signal. The locking program stabilized both lasers to a long term stability of better than 9 MHz, with a custom-built IR laser undergoing significant improvement in frequency stabilization. The results of this study demonstrate the viability of a simple, computer-controlled, non-temperature-stabilized FP locking scheme for our applications, laser cooling of Ca(+) ions, and its use in other applications with similar modest frequency stabilization requirements.

  19. Activation of brain-derived neurotrophic factor/tropomyosin-related kinase B signaling accompanying filial imprinting in domestic chicks (Gallus gallus domesticus).

    Science.gov (United States)

    Yamaguchi, Shinji; Aoki, Naoya; Kobayashi, Daisuke; Kitajima, Takaaki; Iikubo, Eiji; Katagiri, Sachiko; Matsushima, Toshiya; Homma, Koichi J

    2011-12-07

    Newly hatched domestic chicks serve as an important model for experimental studies of neural and behavioral plasticity. Brain-derived neurotrophic factor (BDNF) has been shown to play a critical role in synaptic plasticity, including long-term potentiation, which underlies learning and memory in rodents. Here we show that BDNF mRNA levels increased in the intermediate medial hyperpallium apicale (IMHA), which is the caudal area of the visual Wulst, of imprinted chick brains, and the upregulation of gene expression correlated with the strength of the learned preference to the training object. In addition, activation of tropomyosin-related kinase B (TrkB)/phosphatidylinositol 3-kinase signaling was associated with filial imprinting. However, pharmacological deprivation of TrkB phosphorylation in IMHA did not impair memory formation, suggesting that activation of BDNF/TrkB signaling in IMHA is not involved in memory acquisition in filial imprinting.

  20. Helicobacter pylori-derived Heat shock protein 60 enhances angiogenesis via a CXCR2-mediated signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Chen-Si [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China); School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan (China); He, Pei-Juin; Hsu, Wei-Tung [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China); Wu, Ming-Shiang [Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Wu, Chang-Jer [Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan (China); Shen, Hsiao-Wei [Institute of Molecular Medicine and Bioengineering, National Chiao-Tung University, Hsin-Chu, Taiwan (China); Hwang, Chia-Hsiang [Yung-Shin Pharmaceutical Industry Co., Ltd., Tachia, Taichung, Taiwan (China); Lai, Yiu-Kay [Department of Life Science, Institute of Biotechnology, National Tsing Hua University, Hsin-Chu, Taiwan (China); Tsai, Nu-Man [School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan (China); Liao, Kuang-Wen, E-mail: kitchhen@yahoo.com.tw [Institute of Molecular Medicine and Bioengineering, National Chiao-Tung University, Hsin-Chu, Taiwan (China)

    2010-06-25

    Helicobacter pylori is a potent carcinogen associated with gastric cancer malignancy. Recently, H. pylori Heat shock protein 60 (HpHSP60) has been reported to promote cancer development by inducing chronic inflammation and promoting tumor cell migration. This study demonstrates a role for HpHSP60 in angiogenesis, a necessary precursor to tumor growth. We showed that HpHSP60 enhanced cell migration and tube formation, but not cell proliferation, in human umbilical vein endothelial cells (HUVECs). HpHSP60 also indirectly promoted HUVEC proliferation when HUVECs were co-cultured with supernatants collected from HpHSP60-treated AGS or THP-1 cells. The angiogenic array showed that HpHSP60 dramatically induced THP-1 cells and HUVECs to produce the chemotactic factors IL-8 and GRO. Inhibition of CXCR2, the receptor for IL-8 and GRO, or downstream PLC{beta}2/Ca2+-mediated signaling, significantly abolished HpHSP60-induced tube formation. In contrast, suppression of MAP K or PI3 K signaling did not affect HpHSP60-mediated tubulogenesis. These data suggest that HpHSP60 enhances angiogenesis via CXCR2/PLC{beta}2/Ca2+ signal transduction in endothelial cells.

  1. Heart- and muscle-derived signaling system dependent on MED13 and Wingless controls obesity in Drosophila.

    Science.gov (United States)

    Lee, Ji-Hoon; Bassel-Duby, Rhonda; Olson, Eric N

    2014-07-01

    Obesity develops in response to an imbalance of energy homeostasis and whole-body metabolism. Muscle plays a central role in the control of energy homeostasis through consumption of energy and signaling to adipose tissue. We reported previously that MED13, a subunit of the Mediator complex, acts in the heart to control obesity in mice. To further explore the generality and mechanistic basis of this observation, we investigated the potential influence of MED13 expression in heart and muscle on the susceptibility of Drosophila to obesity. Here, we show that heart/muscle-specific knockdown of MED13 or MED12, another Mediator subunit, increases susceptibility to obesity in adult flies. To identify possible muscle-secreted obesity regulators, we performed an RNAi-based genetic screen of 150 genes that encode secreted proteins and found that Wingless inhibition also caused obesity. Consistent with these findings, muscle-specific inhibition of Armadillo, the downstream transcriptional effector of the Wingless pathway, also evoked an obese phenotype in flies. Epistasis experiments further demonstrated that Wingless functions downstream of MED13 within a muscle-regulatory pathway. Together, these findings reveal an intertissue signaling system in which Wingless acts as an effector of MED13 in heart and muscle and suggest that Wingless-mediated cross-talk between striated muscle and adipose tissue controls obesity in Drosophila. This signaling system appears to represent an ancestral mechanism for the control of systemic energy homeostasis.

  2. CD4+ T cell-derived IL-2 signals during early priming advances primary CD8+ T cell responses.

    Directory of Open Access Journals (Sweden)

    Yo-Ping Lai

    2009-11-01

    Full Text Available Stimulating naïve CD8+ T cells with specific antigens and costimulatory signals is insufficient to induce optimal clonal expansion and effector functions. In this study, we show that the activation and differentiation of CD8+ T cells require IL-2 provided by activated CD4+ T cells at the initial priming stage within 0-2.5 hours after stimulation. This critical IL-2 signal from CD4+ cells is mediated through the IL-2Rbetagamma of CD8+ cells, which is independent of IL-2Ralpha. The activation of IL-2 signaling advances the restriction point of the cell cycle, and thereby expedites the entry of antigen-stimulated CD8+ T-cell into the S phase. Besides promoting cell proliferation, IL-2 stimulation increases the amount of IFNgamma and granzyme B produced by CD8+ T cells. Furthermore, IL-2 at priming enhances the ability of P14 effector cells generated by antigen activation to eradicate B16.gp33 tumors in vivo. Therefore, our studies demonstrate that a full CD8+ T-cell response is elicited by a critical temporal function of IL-2 released from CD4+ T cells, providing mechanistic insights into the regulation of CD8+ T cell activation and differentiation.

  3. Brain derived neurotrophic factor is involved in the regulation of glycogen synthase kinase 3β (GSK3β) signalling

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, Vivek, E-mail: vivek.gupta@mq.edu.au [Australian School of Advanced Medicine, Macquarie University (Australia); Chitranshi, Nitin; You, Yuyi [Australian School of Advanced Medicine, Macquarie University (Australia); Gupta, Veer [School of Medical Sciences, Edith Cowan University, Perth (Australia); Klistorner, Alexander; Graham, Stuart [Australian School of Advanced Medicine, Macquarie University (Australia); Save Sight Institute, Sydney University, Sydney (Australia)

    2014-11-21

    Highlights: • BDNF knockdown leads to activation of GSK3β in the neuronal cells. • BDNF knockdown can induce GSK3β activation beyond TrkB mediated effects. • BDNF impairment in vivo leads to age dependent activation of GSK3β in the retina. • Systemic treatment with TrkB agonist induces inhibition of retinal GSK3β. - Abstract: Glycogen synthase kinase 3β (GSK3β) is involved in several biochemical processes in neurons regulating cellular survival, gene expression, cell fate determination, metabolism and proliferation. GSK3β activity is inhibited through the phosphorylation of its Ser-9 residue. In this study we sought to investigate the role of BDNF/TrkB signalling in the modulation of GSK3β activity. BDNF/TrkB signalling regulates the GSK3β activity both in vivo in the retinal tissue as well as in the neuronal cells under culture conditions. We report here for the first time that BDNF can also regulate GSK3β activity independent of its effects through the TrkB receptor signalling. Knockdown of BDNF lead to a decline in GSK3β phosphorylation without having a detectable effect on the TrkB activity or its downstream effectors Akt and Erk1/2. Treatment with TrkB receptor agonist had a stimulating effect on the GSK3β phosphorylation, but the effect was significantly less pronounced in the cells in which BDNF was knocked down. The use of TrkB receptor antagonist similarly, manifested itself in the form of downregulation of GSK3β phosphorylation, but a combined TrkB inhibition and BDNF knockdown exhibited a much stronger negative effect. In vivo, we observed reduced levels of GSK3β phosphorylation in the retinal tissues of the BDNF{sup +/−} animals implicating critical role of BDNF in the regulation of the GSK3β activity. Concluding, BDNF/TrkB axis strongly regulates the GSK3β activity and BDNF also exhibits GSK3β regulatory effect independent of its actions through the TrkB receptor signalling.

  4. NADPH oxidase-derived H2O2 subverts pathogen signaling by oxidative phosphotyrosine conversion to PB-DOPA

    Science.gov (United States)

    Alvarez, Luis A.; Kovačič, Lidija; Rodríguez, Javier; Gosemann, Jan-Hendrik; Kubica, Malgorzata; Pircalabioru, Gratiela G.; Friedmacher, Florian; Cean, Ada; Ghişe, Alina; Sărăndan, Mihai B.; Puri, Prem; Daff, Simon; Plettner, Erika; von Kriegsheim, Alex; Bourke, Billy; Knaus, Ulla G.

    2016-01-01

    Strengthening the host immune system to fully exploit its potential as antimicrobial defense is vital in countering antibiotic resistance. Chemical compounds released during bidirectional host–pathogen cross-talk, which follows a sensing-response paradigm, can serve as protective mediators. A potent, diffusible messenger is hydrogen peroxide (H2O2), but its consequences on extracellular pathogens are unknown. Here we show that H2O2, released by the host on pathogen contact, subverts the tyrosine signaling network of a number of bacteria accustomed to low-oxygen environments. This defense mechanism uses heme-containing bacterial enzymes with peroxidase-like activity to facilitate phosphotyrosine (p-Tyr) oxidation. An intrabacterial reaction converts p-Tyr to protein-bound dopa (PB-DOPA) via a tyrosinyl radical intermediate, thereby altering antioxidant defense and inactivating enzymes involved in polysaccharide biosynthesis and metabolism. Disruption of bacterial signaling by DOPA modification reveals an infection containment strategy that weakens bacterial fitness and could be a blueprint for antivirulence approaches. PMID:27562167

  5. Differential Signaling and Sugar Exchanges in Response to Avirulent Pathogen- and Symbiont-Derived Molecules in Tobacco Cells

    Directory of Open Access Journals (Sweden)

    Carole Pfister

    2017-11-01

    Full Text Available Plants interact with microbes whose ultimate aim is to exploit plant carbohydrates for their reproduction. Plant–microbe interactions (PMIs are classified according to the nature of their trophic exchanges: while mutualistic microbes trade nutrients with plants, pathogens unilaterally divert carbohydrates. The early responses following microbe recognition and the subsequent control of plant sugar distribution are still poorly understood. To further decipher PMI functionality, we used tobacco cells treated with microbial molecules mimicking pathogenic or mutualistic PMIs, namely cryptogein, a defense elicitor, and chitotetrasaccharide (CO4, which is secreted by mycorrhizal fungi. CO4 was perceived by tobacco cells and triggered widespread transient signaling components such as a sharp cytosolic Ca2+ elevation, NtrbohD-dependent H2O2 production, and MAP kinase activation. These CO4-induced events differed from those induced by cryptogein, i.e., sustained events leading to cell death. Furthermore, cryptogein treatment inhibited glucose and sucrose uptake but not fructose uptake, and promoted the expression of NtSUT and NtSWEET sugar transporters, whereas CO4 had no effect on sugar uptake and only a slight effect on NtSWEET2B expression. Our results suggest that microbial molecules induce different signaling responses that reflect microbial lifestyle and the subsequent outcome of the interaction.

  6. Inhibition of CD8+ T cell derived CD40 signals is necessary but not sufficient for Foxp3+ iTreg induction in vivo

    Science.gov (United States)

    Liu, Danya; Ferrer, Ivana R.; Konomos, Michael; Ford, Mandy L.

    2013-01-01

    Current models of CD4+ T cell help suggest a major role for CD154 binding to CD40 expressed on DC, with a lesser role for direct T: T interactions via CD40 expressed on CD8+ T cells. However, the contribution of CD8+ T cell-derived CD40 signals during the donor-reactive T cell response to a transplant has never been studied. Here, we examined the graft rejection kinetics and CD4+ and CD8+ donor-reactive T cell responses under conditions where CD40 was genetically ablated only on antigen presenting cells, and under conditions where CD40 was genetically ablated only on donor-reactive CD8+ T cells. Our results revealed a significant role for CD8+ T cell-expressed CD40 in the augmentation of donor-reactive CD8+ T cell responses following transplantation, and showed that CD40 expressed on CD8+ T cells must be inhibited to allow conversion of CD4+ T cells into iTreg. Thus, this study identifies a major role of CD8+ T cell-derived CD40 signals as a critical switch factor which both promotes optimal differentiation of cytokine-producing CD8+ effector T cell responses, and inhibits the differentiation of antigen-specific Foxp3+ iTreg vivo. PMID:23858029

  7. Influence оf 2d Vibratory Motion Conveyed to Billet on Force And Timing Parameters of its Contact Interaction With Sawing Disc

    Directory of Open Access Journals (Sweden)

    M. G. Kiselev

    2014-01-01

    Full Text Available The paper presents an experimental investigation on influence of 2D vibratory dimension conveyed to a billet on force and timing parameters of its contact interaction with a sawing disc. Description of the modernized sawing section ensuring conveyance of 2D vibratory motion to a billet, methodology and  hardware facilities applied for normal force measurement of its impact with the disc and longevity of their contact for the period of the billet circulation motion. The paper provides, analyzes and generalizes experimentally obtained dependences reflecting influence of gap clearance between a boom and an upper stop on the mentioned force and timing parameters of the billet contact interaction with the sawing disc.

  8. Effective gene delivery into adipose-derived stem cells: transfection of cells in suspension with the use of a nuclear localization signal peptide-conjugated polyethylenimine.

    Science.gov (United States)

    Park, Eulsoon; Cho, Hong-Baek; Takimoto, Koichi

    2015-05-01

    Adipose-derived stem cells have the ability to turn into several clinically important cell types. However, it is difficult to transfect these cells with the use of conventional cationic lipid-based reagents. Polyethylenimine (PEI) is considered to be an inexpensive and effective tool for delivery of nucleic acids into mammalian cells. We used a linear PEI conjugated with the nuclear localization signal (NLS) peptide of Simian vacuolating virus 40 large T antigen (PEI-NLS) for transfection of plasmid DNA into adipose-derived cells. We also tested if transfection of cells in suspension might improve the degree and duration of exogenous gene expression. Transfection of cells in suspension with the use of a PEI conjugated with an NLS peptide resulted in high levels of reporter gene expression for an extended period of time in clonal 3T3-L1 preadipocytes and native human adipose-derived stem cells. The reporter gene expression increased for 3 days after the addition of the PEI-NLS peptide-DNA mixture in cell suspension and remained significant for at least 7 days. Cell density did not influence the level of reporter gene expression. Thus, the suspension method with the use of an NLS peptide-conjugated PEI leads to a robust and sustained expression of exogenous genes in adipose-derived cells. The devised transfection method may be useful for reprogramming of adipose-derived stem cells and cell-based therapy. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  9. Wnt signalling mediates the cross-talk between bone marrow derived pre-adipocytic and pre-osteoblastic cell populations

    DEFF Research Database (Denmark)

    Taipaleenmaki, Hanna; Abdallah, Basem M; Aldamash, Abdullah

    2011-01-01

    ) (mMSC(Bone)) or adipogenic (mMSC(Adipo)) lineage. To identify the molecular mechanism determining the lineage commitment, we compared the basal gene expression profile of mMSC(Bone) versus mMSC(Adipo) using Affymetrix GeneChip® MG430A 2.0 Array. Gene annotation analysis based on biological function......The mechanisms underlying the inverse relationship between osteogenic and adipogenic differentiation of bone marrow stromal cells (MSC) are not known in detail. We have previously established two cell lines from mouse bone marrow that are committed to either osteogenic (osteoblasts and chondrocytes...... revealed an over-representation of skeletal development genes in mMSC(Bone) while genes related to lipid metabolism and immune response were highly expressed in mMSC(Adipo). In addition, there was a significant up-regulation of canonical Wnt signalling genes in mMSC(Bone) compared to mMSC(Adipo) (p...

  10. The thermodynamic and transport properties of GdCl3 in molten eutectic LiCl-KCl derived from the analysis of cyclic voltammetry signals

    Science.gov (United States)

    Samin, Adib; Wu, Evan; Zhang, Jinsuo

    2017-02-01

    Pyroprocessing technology is a promising tool for recycling nuclear fuel and producing high purity gadolinium for industrial applications. An efficient implementation of pyroprocessing entails a careful characterization of the electrochemical and transport properties of lanthanides in high temperature molten salts. In this work, the cyclic voltammetry signals of Gd in molten LiCl-KCl salt were recorded for a combination of three temperatures (723 K, 773 K, and 823 K) and three concentration levels (3 wt. %, 6 wt. %, and 9 wt. %) including concentration levels higher than previously reported and relevant for a realistic application of pyroprocessing for molten salt recycle, and the concentration effects were investigated. Four scan rates (200 mV/s to 500 mV/s) were used for each condition, and the signals were examined using conventional Cyclic Voltammetry (CV) analysis equations and by utilizing a two-plate Brunauer, Emmett, and Teller (BET) model accounting for mass diffusion, kinetics, adsorption, and the evolution of electrode morphology via a nonlinear least squares procedure for fitting the model to the experimental signals. It was determined that the redox process is quasi-reversible for the scan rates being used. Furthermore, the applicability of the conventional equations for CV analysis was shown to be problematic for the conditions used, and this is thought to be due to the fact that these equations were derived under the assumption of reversible conditions. The model-derived values for diffusivity are consistent with the literature and are shown to decrease with increasing concentration. This may be due to increased interactions at higher concentration levels. It was also shown that the formal redox potential increased with a concentration and was slightly more positive on the covered electrode.

  11. Increased heme-oxygenase 1 expression in mesenchymal stem cell-derived adipocytes decreases differentiation and lipid accumulation via upregulation of the canonical Wnt signaling cascade.

    Science.gov (United States)

    Vanella, Luca; Sodhi, Komal; Kim, Dong Hyun; Puri, Nitin; Maheshwari, Mani; Hinds, Terry D; Bellner, Lars; Goldstein, Dov; Peterson, Stephen J; Shapiro, Joseph I; Abraham, Nader G

    2013-03-12

    Heme oxygenase (HO), a major cytoprotective enzyme, attenuates oxidative stress and obesity. The canonical Wnt signaling cascade plays a pivotal role in the regulation of adipogenesis. The present study examined the interplay between HO-1and the Wnt canonical pathway in the modulation of adipogenesis in mesenchymal stem cell (MSC)-derived adipocytes. To verify the role of HO-1 in generating small healthy adipocytes, cobalt protoporphyrin (CoPP), inducer of HO-1, was used during adipocyte differentiation. Lipid accumulation was measured by Oil red O staining and lipid droplet size was measured by BODIPY staining. During adipogenesis in vitro, differentiating pre-adipocytes display transient increases in the expression of genes involved in canonical Wnt signaling cascade. Increased levels of HO-1 expression and HO activity resulted in elevated levels of β-catenin, pGSK3β, Wnt10b, Pref-1, and shh along with increased levels of adiponectin (P reduction in C/EBPα, PPARγ, Peg-1/Mest, aP2, CD36 expression and lipid accumulation (P adipocyte differentiation suggesting that the HO-1 mediated increase in Wnt10b can modulate the adipocyte phenotype by regulating the transcriptional factors that play a role in adipogenesis. This is evidenced by a decrease in lipid accumulation and inflammatory cytokine levels, increased adiponectin levels and elevation of the expression of genes of the canonical Wnt signaling cascade.

  12. Differences in joint-position sense and vibratory threshold in runners with and without a history of overuse injury.

    Science.gov (United States)

    Switlick, Tiffany; Kernozek, Thomas W; Meardon, Stacey

    2015-02-01

    A relationship between altered postural control and injury has been reported in sports. Sensorimotor function serves a fundamental role in postural control and is not often studied in runners. Persons who sustain running injury may have altered sensorimotor function contributing to risk of injury or reinjury. To determine if differences in knee and ankle proprioception or plantar sensation exist between injured and noninjured runners. Retrospective case-control study. University campus. Twenty runners with a history of lower-extremity overuse injury and 20 noninjured runners were examined. Injured runners were subcategorized into 2 groups based on site of injury: foot/ankle and knee/hip. Active absolute joint-repositioning error of the ankle at 20° inversion and 10° eversion and the knee at 15° and 40° flexion was assessed using an isokinetic dynamometer. Vibratory threshold at the calcaneus, arch, and great toe was determined for each subject using a handheld electric sensory threshold instrument. Runners in the injured-foot/ankle group had increased absolute error during ankle-eversion repositioning (6.55° ± 3.58°) compared with those in the noninjured (4.04° ± 1.78°, P = .01) and the hip/knee (3.63° ± 2.2°, P = .01) groups. Runners in the injured group, as a whole, had greater sensitivity in the arch of the plantar surface (2.94 ± 0.52 V) than noninjured runners (2.38 ± 0.53 V, P = .02). Differences in ankle-eversion proprioception between runners with a history of ankle and foot injuries and noninjured runners were observed. Runners with a history of injury also displayed an increased vibratory threshold in the arch region compared with noninjured runners. Poor ankle-joint-position sense and increased plantar sensitivity suggest altered sensorimotor function after injury. These factors may influence underlying postural control and contribute to altered loading responses commonly observed in injured runners.

  13. Low-frequency vibratory exercise reduces the risk of bone fracture more than walking: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Leal Alejo

    2006-11-01

    Full Text Available Abstract Background Whole-body vibration (WBV is a new type of exercise that has been increasingly tested for the ability to prevent bone fractures and osteoporosis in frail people. There are two currently marketed vibrating plates: a the whole plate oscillates up and down; b reciprocating vertical displacements on the left and right side of a fulcrum, increasing the lateral accelerations. A few studies have shown recently the effectiveness of the up-and-down plate for increasing Bone Mineral Density (BMD and balance; but the effectiveness of the reciprocating plate technique remains mainly unknown. The aim was to compare the effects of WBV using a reciprocating platform at frequencies lower than 20 Hz and a walking-based exercise programme on BMD and balance in post-menopausal women. Methods Twenty-eight physically untrained post-menopausal women were assigned at random to a WBV group or a Walking group. Both experimental programmes consisted of 3 sessions per week for 8 months. Each vibratory session included 6 bouts of 1 min (12.6 Hz in frequency and 3 cm in amplitude with 60° of knee flexion with 1 min rest between bouts. Each walking session was 55 minutes of walking and 5 minutes of stretching. Hip and lumbar BMD (g·cm-2 were measured using dual-energy X-ray absorptiometry and balance was assessed by the blind flamingo test. ANOVA for repeated measurements was adjusted by baseline data, weight and age. Results After 8 months, BMD at the femoral neck in the WBV group was increased by 4.3% (P = 0.011 compared to the Walking group. In contrast, the BMD at the lumbar spine was unaltered in both groups. Balance was improved in the WBV group (29% but not in the Walking group. Conclusion The 8-month course of vibratory exercise using a reciprocating plate is feasible and is more effective than walking to improve two major determinants of bone fractures: hip BMD and balance.

  14. Influence of the Radial Clearance of a Squeeze Film Damper on the Vibratory Behavior of a Single Spool Gas Turbine Designed for Unmanned Aerial Vehicle Applications

    OpenAIRE

    Geraldo Creci; José Orlando Balastrero; Sidney Domingues; Luis Vanderlei Torres; João Carlos Menezes

    2017-01-01

    This study presents a numerical investigation using the finite element method on the vibratory behavior of a single spool gas turbine designed for unmanned aerial vehicle applications. The shaft of the rotor-bearing system is supported on a front bearing composed of a deep groove ball bearing with a vibration absorber element and a rear squeeze film damper bearing. Three radial clearances for the squeeze film damper were analyzed to determine the best geometric configuration for the rear bear...

  15. CD20-selective inhibition of CD47-SIRPα "don't eat me" signaling with a bispecific antibody-derivative enhances the anticancer activity of daratumumab, alemtuzumab and obinutuzumab

    NARCIS (Netherlands)

    van Bommel, Peter E; He, Yuan; Schepel, Ilona; Hendriks, Mark A J M; Wiersma, Valerie R; van Ginkel, Robert J; van Meerten, Tom; Ammatuna, Emanuele; Huls, Gerwin; Samplonius, Douwe F; Helfrich, Wijnand; Bremer, Edwin

    2018-01-01

    Here, we report on a novel bispecific antibody-derivative, designated RTX-CD47, with unique capacity for CD20-directed inhibition of CD47-SIRPα "don't eat me" signaling. RTX-CD47 comprises a CD20-targeting scFv antibody fragment derived from rituximab fused in tandem to a CD47-blocking scFv. Single

  16. TNF-TNFR2/p75 Signaling Inhibits Early and Increases Delayed Nontargeted Effects in Bone Marrow-derived Endothelial Progenitor Cells*

    Science.gov (United States)

    Sasi, Sharath P.; Song, Jin; Park, Daniel; Enderling, Heiko; McDonald, J. Tyson; Gee, Hannah; Garrity, Brittany; Shtifman, Alexander; Yan, Xinhua; Walsh, Kenneth; Natarajan, Mohan; Kishore, Raj; Goukassian, David A.

    2014-01-01

    TNF-α, a pro-inflammatory cytokine, is highly expressed after being irradiated (IR) and is implicated in mediating radiobiological bystander responses (RBRs). Little is known about specific TNF receptors in regulating TNF-induced RBR in bone marrow-derived endothelial progenitor cells (BM-EPCs). Full body γ-IR WT BM-EPCs showed a biphasic response: slow decay of p-H2AX foci during the initial 24 h and increase between 24 h and 7 days post-IR, indicating a significant RBR in BM-EPCs in vivo. Individual TNF receptor (TNFR) signaling in RBR was evaluated in BM-EPCs from WT, TNFR1/p55KO, and TNFR2/p75KO mice, in vitro. Compared with WT, early RBR (1–5 h) were inhibited in p55KO and p75KO EPCs, whereas delayed RBR (3–5 days) were amplified in p55KO EPCs, suggesting a possible role for TNFR2/p75 signaling in delayed RBR. Neutralizing TNF in γ-IR conditioned media (CM) of WT and p55KO BM-EPCs largely abolished RBR in both cell types. ELISA protein profiling of WT and p55KO EPC γ-IR-CM over 5 days showed significant increases in several pro-inflammatory cytokines, including TNF-α, IL-1α (Interleukin-1 alpha), RANTES (regulated on activation, normal T cell expressed and secreted), and MCP-1. In vitro treatments with murine recombinant (rm) TNF-α and rmIL-1α, but not rmMCP-1 or rmRANTES, increased the formation of p-H2AX foci in nonirradiated p55KO EPCs. We conclude that TNF-TNFR2 signaling may induce RBR in naïve BM-EPCs and that blocking TNF-TNFR2 signaling may prevent delayed RBR in BM-EPCs, conceivably, in bone marrow milieu in general. PMID:24711449

  17. mTOR signaling disruption from myeloid-derived suppressive cells protects against immune-mediated hepatic injury through the HIF1α-dependent glycolytic pathway.

    Science.gov (United States)

    Chen, Xi; Zhang, Zhengguo; Bi, Yujing; Fu, Zan; Gong, Pingsheng; Li, Yan; Yu, Qing; Jia, Anna; Wang, Jian; Xue, Lixiang; Yang, Hui; Liu, Guangwei

    2016-12-01

    The mechanistic target of rapamycin (mTOR) pathway integrates diverse environmental inputs, including immune signals and metabolic cues, to direct innate and adaptive immune responses. Myeloid-derived suppressive cells (MDSCs) are a heterogeneous cell population that plays a crucial regulatory effect in immune-related diseases. However, whether mTOR signaling affects the functions of MDSCs remains largely unexplored. Here, we show that mTOR signaling is a pivotal, negative determinant of MDSC function in immune-mediated hepatic injury (IMH) diseases. In the context of IMH, the blocking of mTOR with rapamycin or mTOR-deficient CD11b+Gr1+ MDSCs mediates the protection against IMH; mTOR with rapamycin and mTOR-deficient CD11b+Gr1+ MDSCs are suppressive immune modulators that result in less IFN-γ-producing TH1 cells and more Foxp3+ Tregs Mechanistically, mTOR activity down-regulation in MDSCs induced iNOS expressions and NO productions. Pharmacologic inhibitions of iNOS completely eliminate MDSC-suppressive function and lose their inducible effects on T cell differentiation. Importantly, HIF1α-dependent glycolytic activity is responsible for mTOR-deficient, increased MDSC functional changes in IMH inflammation. Thus, these data demonstrate that mTOR acts as a fundamental "rheostat" in MDSCs to link immunologic signals to glycolytic pathways and functional fitness and highlights a central role of metabolic programming of MDSC-suppressive activity in protecting against immune hepatic injuries. © Society for Leukocyte Biology.

  18. Lysophosphatidic acid signaling through its receptor initiates profibrotic epithelial cell fibroblast communication mediated by epithelial cell derived connective tissue growth factor.

    Science.gov (United States)

    Sakai, Norihiko; Chun, Jerold; Duffield, Jeremy S; Lagares, David; Wada, Takashi; Luster, Andrew D; Tager, Andrew M

    2017-03-01

    The expansion of the fibroblast pool is a critical step in organ fibrosis, but the mechanisms driving expansion remain to be fully clarified. We previously showed that lysophosphatidic acid (LPA) signaling through its receptor LPA1 expressed on fibroblasts directly induces the recruitment of these cells. Here we tested whether LPA-LPA1 signaling drives fibroblast proliferation and activation during the development of renal fibrosis. LPA1-deficient (LPA1-/-) or -sufficient (LPA1+/+) mice were crossed to mice with green fluorescent protein expression (GFP) driven by the type I procollagen promoter (Col-GFP) to identify fibroblasts. Unilateral ureteral obstruction-induced increases in renal collagen were significantly, though not completely, attenuated in LPA1-/-Col-GFP mice, as were the accumulations of both fibroblasts and myofibroblasts. Connective tissue growth factor was detected mainly in tubular epithelial cells, and its levels were suppressed in LPA1-/-Col-GFP mice. LPA-LPA1 signaling directly induced connective tissue growth factor expression in primary proximal tubular epithelial cells, through a myocardin-related transcription factor-serum response factor pathway. Proximal tubular epithelial cell-derived connective tissue growth factor mediated renal fibroblast proliferation and myofibroblast differentiation. Administration of an inhibitor of myocardin-related transcription factor/serum response factor suppressed obstruction-induced renal fibrosis. Thus, targeting LPA-LPA1 signaling and/or myocardin-related transcription factor/serum response factor-induced transcription could be promising therapeutic strategies for renal fibrosis. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  19. Impaired IFNγ-Signaling and Mycobacterial Clearance in IFNγR1-Deficient Human iPSC-Derived Macrophages

    Directory of Open Access Journals (Sweden)

    Anna-Lena Neehus

    2018-01-01

    Full Text Available Mendelian susceptibility to mycobacterial disease (MSMD is caused by inborn errors of interferon gamma (IFNγ immunity and is characterized by severe infections by weakly virulent mycobacteria. Although IFNγ is the macrophage-activating factor, macrophages from these patients have never been studied. We demonstrate the generation of heterozygous and compound heterozygous (iMSMD-cohet induced pluripotent stem cells (iPSCs from a single chimeric patient, who suffered from complete autosomal recessive IFNγR1 deficiency and received bone-marrow transplantation. Loss of IFNγR1 expression had no influence on the macrophage differentiation potential of patient-specific iPSCs. In contrast, lack of IFNγR1 in iMSMD-cohet macrophages abolished IFNγ-dependent phosphorylation of STAT1 and induction of IFNγ-downstream targets such as IRF-1, SOCS-3, and IDO. As a consequence, iMSMD-cohet macrophages show impaired upregulation of HLA-DR and reduced intracellular killing of Bacillus Calmette-Guérin. We provide a disease-modeling platform that might be suited to investigate novel treatment options for MSMD and to gain insights into IFNγ signaling in macrophages.

  20. Brain-derived neurotrophic factor signaling in the HVC is required for testosterone-induced song of female canaries.

    Science.gov (United States)

    Hartog, Tessa E; Dittrich, Falk; Pieneman, Anton W; Jansen, René F; Frankl-Vilches, Carolina; Lessmann, Volkmar; Lilliehook, Christina; Goldman, Steven A; Gahr, Manfred

    2009-12-09

    Testosterone-induced singing in songbirds is thought to involve testosterone-dependent morphological changes that include angiogenesis and neuronal recruitment into the HVC, a central part of the song control circuit. Previous work showed that testosterone induces the production of vascular endothelial growth factor (VEGF) and its receptor (VEGFR2 tyrosine kinase), which in turn leads to an upregulation of brain-derived neurotrophic factor (BDNF) production in HVC endothelial cells. Here we report for the first time that systemic inhibition of the VEGFR2 tyrosine kinase is sufficient to block testosterone-induced song in adult female canaries, despite sustained androgen exposure and the persistence of the effects of testosterone on HVC morphology. Expression of exogenous BDNF in HVC, induced locally by in situ transfection, reversed the VEGFR2 inhibition-mediated blockade of song development, thereby restoring the behavioral phenotype associated with androgen-induced song. The VEGFR2-inhibited, BDNF-treated females developed elaborate male-like song that included large syllable repertoires and high syllable repetition rates, features known to attract females. Importantly, although functionally competent new neurons were recruited to HVC after testosterone treatment, the time course of neuronal addition appeared to follow BDNF-induced song development. These findings indicate that testosterone-associated VEGFR2 activity is required for androgen-induced song in adult songbirds and that the behavioral effects of VEGFR2 inhibition can be rescued by BDNF within the adult HVC.

  1. Brain-Derived Neurotrophic Factor Signaling in the HVC Is Required for Testosterone-Induced Song of Female Canaries

    Science.gov (United States)

    Hartog, Tessa E.; Dittrich, Falk; Pieneman, Anton W.; Jansen, René F.; Frankl-Vilches, Carolina; Lessmann, Volkmar; Lilliehook, Christina; Goldman, Steven A.; Gahr, Manfred

    2012-01-01

    Testosterone-induced singing in songbirds is thought to involve testosterone-dependent morphological changes that include angiogenesis and neuronal recruitment into the HVC, a central part of the song control circuit. Previous work showed that testosterone induces the production of vascular endothelial growth factor (VEGF) and its receptor (VEGFR2 tyrosine kinase), which in turn leads to an upregulation of brain-derived neurotrophic factor (BDNF) production in HVC endothelial cells. Here we report for the first time that systemic inhibition of the VEGFR2 tyrosine kinase is sufficient to block testosterone-induced song in adult female canaries, despite sustained androgen exposure and the persistence of the effects of testosterone on HVC morphology. Expression of exogenous BDNF in HVC, induced locally by in situ transfection, reversed the VEGFR2 inhibition-mediated blockade of song development, thereby restoring the behavioral phenotype associated with androgen-induced song. The VEGFR2-inhibited, BDNF-treated females developed elaborate male-like song that included large syllable repertoires and high syllable repetition rates, features known to attract females. Importantly, although functionally competent new neurons were recruited to HVC after testosterone treatment, the time course of neuronal addition appeared to follow BDNF-induced song development. These findings indicate that testosterone-associated VEGFR2 activity is required for androgen-induced song in adult songbirds and that the behavioral effects of VEGFR2 inhibition can be rescued by BDNF within the adult HVC. PMID:20007475

  2. Electroporated Antigen-Encoding mRNA Is Not a Danger Signal to Human Mature Monocyte-Derived Dendritic Cells

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    Stefanie Hoyer

    2015-01-01

    Full Text Available For therapeutic cancer vaccination, the adoptive transfer of mRNA-electroporated dendritic cells (DCs is frequently performed, usually with monocyte-derived, cytokine-matured DCs (moDCs. However, DCs are rich in danger-sensing receptors which could recognize the exogenously delivered mRNA and induce DC activation, hence influencing the DCs’ immunogenicity. Therefore, we examined whether electroporation of mRNA with a proper cap and a poly-A tail of at least 64 adenosines had any influence on cocktail-matured moDCs. We used 16 different RNAs, encoding tumor antigens (MelanA, NRAS, BRAF, GNAQ, GNA11, and WT1, and variants thereof. None of those RNAs induced changes in the expression of CD25, CD40, CD83, CD86, and CD70 or the secretion of the cytokines IL-8, IL-6, and TNFα of more than 1.5-fold compared to the control condition, while an mRNA encoding an NF-κB-activation protein as positive control induced massive secretion of the cytokines. To determine whether mRNA electroporation had any effect on the whole transcriptome of the DCs, we performed microarray analyses of DCs of 6 different donors. None of 60,000 probes was significantly different between mock-electroporated DCs and MelanA-transfected DCs. Hence, we conclude that no transcriptional programs were induced within cocktail-matured DCs by electroporation of single tumor-antigen-encoding mRNAs.

  3. C3a-derived peptide binds to the type I FcepsilonR and inhibits proximal-coupling signal processes and cytokine secretion by mast cells.

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    Péterfy, Hajna; Tóth, Gábor; Pecht, Israel; Erdei, Anna

    2008-10-01

    A peptide with the natural sequence derived from the complement component C3a, designated C3a7, and C3a9, having a modified sequence of that, was previously shown to inhibit the high-affinity IgER (FcepsilonRI)-induced secretory response of both mucosal and serosal-type mast cells. In addition, several processes that couple the FcepsilonRI stimulus to the cellular response were all suppressed in the presence of these peptides. Here, we show that peptide C3a9 binds to the FcepsilonRI on the surface of unperturbed mast cells (rat mucosal-type RBL-2H3 cell line) and remains bound even after FcepsilonRI-IgE aggregation by antigen as assessed by confocal microscopy. Moreover, that peptide interferes the initial steps of FcepsilonRI-coupling network. Namely, peptide binding to the FcepsilonRI beta-chain interrupts this chain's association with both src family protein tyrosine kinases Lyn and Fyn and enhances the internalization of the receptor. C3a9 was further found to inhibit the phosphorylation of two members of the mitogen-activated protein kinase family, extracellular signal-regulated kinase (ERK) and p38. Although ERK is usually activated via the ras-raf-mitogen-activated protein kinase/ERK kinase (MEK) pathway, our results show that C3a9 has no effect on the c-raf phosphorylation, suggesting that this complement-derived peptide inhibits ERK activation via an alternative route. C3a9 also inhibits the late-phase response to FcepsilonRI stimulus of bone marrow-derived mast cells, reducing secretion of the inflammatory cytokines IL-6 and tumor necrosis factor-alpha. Taken together, the consequence of its interference with the earliest steps of FcepsilonRI stimulus-response coupling and the C3a-derived peptide inhibits both the immediate and the late-phase responses of mast cells.

  4. Microparticles from kidney-derived mesenchymal stem cells act as carriers of proangiogenic signals and contribute to recovery from acute kidney injury.

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    Hoon Young Choi

    Full Text Available We recently demonstrated the use of in vitro expanded kidney-derived mesenchymal stem cells (KMSC protected peritubular capillary endothelial cells in acute renal ischemia-reperfusion injury. Herein, we isolated and characterized microparticles (MPs from KMSC. We investigated their in vitro biologic effects on human endothelial cells and in vivo renoprotective effects in acute ischemia-reperfusion renal injury. MPs were isolated from the supernatants of KMSC cultured in anoxic conditions in serum-deprived media for 24 hours. KMSC-derived MPs demonstrated the presence of several adhesion molecules normally expressed on KMSC membranes, such as CD29, CD44, CD73, α4, 5, and 6 integrins. Quantitative real time PCR confirmed the presence of 3 splicing variants of VEGF-A (120, 164, 188, bFGF and IGF-1 in isolated MPs. MPs labeled with PKH26 red fluorescence dye were incorporated by cultured human umbilical vein endothelial cells (HUVEC via surface molecules such as CD44, CD29, and α4, 5, and 6 integrins. MP dose dependently improved in vitro HUVEC proliferation and promoted endothelial tube formation on growth factor reduced Matrigel. Moreover, apoptosis of human microvascular endothelial cell was inhibited by MPs. Administration of KMSC-derived MPs into mice with acute renal ischemia was followed by selective engraftment in ischemic kidneys and significant improvement in renal function. This was achieved by improving proliferation, of peritubular capillary endothelial cell and amelioration of peritubular microvascular rarefaction. Our results support the hypothesis that KMSC-derived MPs may act as a source of proangiogenic signals and confer renoprotective effects in ischemic kidneys.

  5. Joint position sense and vibratory perception sense in patients with Ehlers-Danlos syndrome type III (hypermobility type).

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    Rombaut, Lies; De Paepe, Anne; Malfait, Fransiska; Cools, Ann; Calders, Patrick

    2010-03-01

    Neurophysiological deficits could make patients with Ehlers-Danlos syndrome (EDS) type III (hypermobility type) more vulnerable to musculoskeletal problems, particularly to joint instability. The purpose of this study was to investigate whether joint position sense (JPS) and vibratory perception sense (VPS) in EDS type III patients in the knee and shoulder joints are impaired. Thirty-two female EDS type III patients as defined by the Villefranche criteria and 32 individually gender- and age-matched healthy control subjects were included in the study. Range of motion was determined using a goniometer, passive and active JPS were assessed with an isokinetic dynamometer system, and the VPS was measured by a biothesiometer. Daily physical activity was evaluated by the Baecke questionnaire. The EDS type III group showed significantly larger ranges of movement (P physical activity (SPA) compared to the control group (P = 0.023). Considering SPA as covariate, the EDS type III group demonstrated a significant impairment in knee joint reposition compared to the control group (P = 0.018). No significant differences were found for shoulder JPS. The VPS was not significantly different in the EDS type III group compared to the control group. In addition, no significant correlation was found between JPS and VPS, neither at the knee nor at the shoulder joint. This is the first study examining proprioception deficits in EDS type III patients as defined by the Villefranche criteria. Further research on the neurophysiological dysfunctions and mechanisms in this pathologic entity is needed.

  6. Design and Analysis of a Novel Fully Decoupled Tri-axis Linear Vibratory Gyroscope with Matched Modes.

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    Xia, Dunzhu; Kong, Lun; Gao, Haiyu

    2015-07-13

    We present in this paper a novel fully decoupled silicon micromachined tri-axis linear vibratory gyroscope. The proposed gyroscope structure is highly symmetrical and can be limited to an area of about 8.5 mm × 8.5 mm. It can differentially detect three axes' angular velocities at the same time. By elaborately arranging different beams, anchors and sensing frames, the drive and sense modes are fully decoupled from each other. Moreover, the quadrature error correction and frequency tuning functions are taken into consideration in the structure design for all the sense modes. Since there exists an unwanted in-plane rotational mode, theoretical analysis is implemented to eliminate it. To accelerate the mode matching process, the particle swam optimization (PSO) algorithm is adopted and a frequency split of 149 Hz is first achieved by this method. Then, after two steps of manual adjustment of the springs' dimensions, the frequency gap is further decreased to 3 Hz. With the help of the finite element method (FEM) software ANSYS, the natural frequencies of drive, yaw, and pitch/roll modes are found to be 14,017 Hz, 14,018 Hz and 14,020 Hz, respectively. The cross-axis effect and scale factor of each mode are also simulated. All the simulation results are in good accordance with the theoretical analysis, which means the design is effective and worthy of further investigation on the integration of tri-axis accelerometers on the same single chip to form an inertial measurement unit.

  7. Experimental Investigation on the Fatigue Life of Ti-6Al-4V Treated by Vibratory Stress Relief

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    Han-Jun Gao

    2017-05-01

    Full Text Available Vibratory stress relief (VSR is a highly efficient and low-energy consumption method to relieve and homogenize residual stresses in materials. Thus, the effect of VSR on the fatigue life should be determined. Standard fatigue specimens are fabricated to investigate the fatigue life of Ti-6Al-4V titanium alloy treated by VSR. The dynamic stresses generated under different VSR amplitudes are measured, and then the relationship between the dynamic stress and vibration amplitude is obtained. Different specimen groups are subjected to VSRs with different amplitudes and annealing treatment with typical process parameters. Residual stresses are measured to evaluate the stress relieving effects. Finally, the fatigue behavior under different states is determined by uniaxial tension–compression fatigue experiments. Results show that VSR and annealing treatment have negative effects on the fatigue life of Ti-6Al-4V. The fatigue life is decreased with the increase in VSR amplitude. When the VSR amplitude is less than 0.1 mm, the decrease in fatigue limit is less than 2%. Compared with specimens without VSR or annealing treatment, the fatigue limit of the specimens treated by VSR with 0.2 mm amplitude and annealing treatment decreases by 10.60% and 8.52%, respectively. Although the stress relieving effect is better, high amplitude VSR will lead to the decrease of Ti-6Al-4V fatigue life due to the defects generated during vibration. Low amplitude VSR can effectively relieve the stress with little decrease in fatigue life.

  8. Anesthetic block of the dorsal penile nerve inhibits vibratory-induced ejaculation in men with spinal cord injuries.

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    Wieder, J A; Brackett, N L; Lynne, C M; Green, J T; Aballa, T C

    2000-06-01

    [corrected] We investigated which nerve pathways are necessary to achieve ejaculation using penile vibratory stimulation (PVS) in men with spinal cord injury (SCI). Eight men with SCI were selected based on the presence of a bulbocavernosus reflex (BCR) and consistent antegrade ejaculation with PVS. Level of injury was cervical (4), upper thoracic (4), and lower thoracic (1). Mean age was 30.4 years (range 22 to 38). Usual responses to PVS included autonomic dysreflexia (4), erection (4), and consistent somatic responses such as abdominal contractions (8). Local anesthesia of the dorsal penile nerves (penile block) was achieved using 1% plain lidocaine injection. Effective penile block was confirmed by loss of the BCR. Two PVS ejaculation trials were performed: one trial during the penile block and one trial when the penile block had worn off. In 4 subjects, the bladder contents were analyzed for retrograde ejaculation. With the penile block, ejaculation was inhibited in 100% of the subjects. None of the bladder washings demonstrated sperm, indicating absence of retrograde ejaculation. None of the subjects exhibited their usual erectile response, somatic responses, or signs of autonomic dysreflexia. After the penile block wore off, PVS induced ejaculation in all subjects. If subjects usually had erection, somatic responses, or signs of autonomic dysreflexia, these also returned. Our data suggest that ejaculatory response to PVS in SCI men requires the presence of intact dorsal penile nerves.

  9. A CALM-derived nuclear export signal is essential for CALM-AF10–mediated leukemogenesis

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    Conway, Amanda E.; Scotland, Paula B.; Lavau, Catherine P.

    2013-01-01

    The t(10;11) chromosomal translocation gives rise to the CALM-AF10 fusion gene and is found in patients with aggressive and difficult-to-treat hematopoietic malignancies. CALM-AF10–driven leukemias are characterized by HOXA gene up-regulation and a global reduction in H3K79 methylation. DOT1L, the H3K79 methyltransferase, interacts with the octapeptide/leucine zipper domain of AF10, and this region has been shown to be necessary and sufficient for CALM-AF10–mediated transformation. However, the precise role of CALM in leukemogenesis remains unclear. Here, we show that CALM contains a nuclear export signal (NES) that mediates cytoplasmic localization of CALM-AF10 and is necessary for CALM-AF10–dependent transformation. Fusions of the CALM NES (NESCALM-AF10) or NES motifs from heterologous proteins (ABL1, Rev, PKIA, APC) in-frame with AF10 are sufficient to immortalize murine hematopoietic progenitors in vitro. The CALM NES is essential for CALM-AF10–dependent Hoxa gene up-regulation and aberrant H3K79 methylation, possibly by mislocalization of DOT1L. Finally, we observed that CALM-AF10 leukemia cells are selectively sensitive to inhibition of nuclear export by Leptomycin B. These findings uncover a novel mechanism of leukemogenesis mediated by the nuclear export pathway and support further investigation of the utility of nuclear export inhibitors as therapeutic agents for patients with CALM-AF10 leukemias. PMID:23487024

  10. The E3 Ubiquitin Ligase WWP1 Selectively Targets HER4 and Its Proteolytically Derived Signaling Isoforms for Degradation▿

    Science.gov (United States)

    Feng, Shu-Mang; Muraoka-Cook, Rebecca S.; Hunter, Debra; Sandahl, Melissa A.; Caskey, Laura S.; Miyazawa, Keiji; Atfi, Azeddine; Earp, H. Shelton

    2009-01-01

    In general, epidermal growth factor receptor family members stimulate cell proliferation. In contrast, at least one HER4 isoform, JM-a/Cyt1, inhibits cell growth after undergoing a two-step proteolytic cleavage that first produces a membrane-anchored 80-kDa fragment (m80HER4) and subsequently liberates a soluble 80-kDa fragment, s80HER4. Here we report that s80HER4 Cyt1 action increased the expression of WWP1 (for WW domain-containing protein 1), an E3 ubiquitin ligase, but not other members of the Nedd4 E3 ligase family. The HER4 Cyt1 isoform contains three proline-rich tyrosine (PY) WW binding motifs, while Cyt2 has only two. WWP1 binds to all three Cyt1 PY motifs; the interaction with PY2 found exclusively in Cyt1 was strongest. WWP1 ubiquitinated and caused the degradation of HER4 but not of EGFR, HER2, or HER3. The HER4-WWP1 interaction also accelerated WWP1 degradation. Membrane HER4 (full length and m80HER4, the product of the first proteolytic cleavage) were the preferred targets of WWP1, correlating with the membrane localization of WWP1. Conversely s80HER4, a poorer WWP1 substrate, was found in the cell nucleus, while WWP1 was not. Deletion of the C2 membrane association domain of WWP1 allowed more efficient s80HER4 degradation, suggesting that WWP1 is normally part of a membrane complex that regulates HER4 membrane species levels, with a predilection for the growth-inhibitory Cyt1 isoform. Finally, WWP1 expression diminished HER4 biologic activity in MCF-7 cells. We previously showed that nuclear s80HER4 is ubiquitinated and degraded by the anaphase-promoting complex, suggesting that HER4 ubiquitination within specific cellular compartments helps regulate the unique HER4 signaling capabilities. PMID:19047365

  11. A novel synthetic derivative of melatonin, 5-hydroxy-2'-isobutyl-streptochlorin (HIS), inhibits inflammatory responses via regulation of TRIF-dependent signaling and inflammasome activation.

    Science.gov (United States)

    Shim, Do-Wan; Shin, Hee Jae; Han, Ji-Won; Ji, Young-Eun; Jang, Cheol-Hun; Koppula, Sushruta; Kang, Tae-Bong; Lee, Kwang-Ho

    2015-04-15

    Melatonin is substantially reported to possess anti-inflammatory properties. In the present study, we synthesized a novel melatonin derivative, 5-hydroxy-2'-isobutyl-streptochlorin (HIS), which displayed superior anti-inflammatory properties to its parent compound. Further, we explored its underlying mechanisms in cellular and experimental animal models. Lipopolysaccharide was used to induce in vitro inflammatory responses in RAW 264.7 macrophages. LPS-primed macrophages were pulsed with biologically unrelated toxic molecules to evaluate the role of HIS on inflammasome activation. In vivo verifications were carried out using acute lung injury (ALI) and Escherichia coli-induced septic shock mouse models. HIS inhibited the production of proinflammatory mediators and cytokines such as nitric oxide, cyclooxygenase 2, IL-1β, IL-6 and TNF-α in LPS-stimulated RAW 264.7 macrophages. HIS suppressed the infiltration of immune cells into the lung and the production of pro-inflammatory cytokines such as IL-6 and TNF-α in broncho-alveolar lavage fluid in the ALI mouse model. Mechanistic studies revealed that the inhibitory effects of HIS were mediated through the regulation of the TIR domain-containing, adaptor-inducing, interferon-β (TRIF)-dependent signaling pathway from toll-like receptors. Further, HIS attenuated IL-1β secretion via the inhibition of NLRP3 inflammasome activation independent of mitochondrial ROS production. Furthermore, HIS suppressed IL-1β, IL-6 and interferon-β production in peritoneal lavage in the Escherichia coli-induced sepsis mouse model. In conclusion, HIS exerted potent anti-inflammatory effects via the regulation of TRIF-dependent signaling and inflammasome activation. Notably, the superior anti-inflammatory properties of this derivative compared with its parent compound could be a promising lead for treating various inflammatory-mediated diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Angiotensin II-dependent hypertension requires cyclooxygenase 1-derived prostaglandin E2 and EP1 receptor signaling in the subfornical organ of the brain.

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    Cao, Xian; Peterson, Jeffrey R; Wang, Gang; Anrather, Josef; Young, Colin N; Guruju, Mallikarjuna R; Burmeister, Melissa A; Iadecola, Costantino; Davisson, Robin L

    2012-04-01

    Cyclooxygenase (COX)-derived prostanoids have long been implicated in blood pressure (BP) regulation. Recently prostaglandin E(2) (PGE(2)) and its receptor EP(1) (EP(1)R) have emerged as key players in angiotensin II (Ang II)-dependent hypertension (HTN) and related end-organ damage. However, the enzymatic source of PGE(2,) that is, COX-1 or COX-2, and its site(s) of action are not known. The subfornical organ (SFO) is a key forebrain region that mediates systemic Ang II-dependent HTN via reactive oxygen species (ROS). We tested the hypothesis that cross-talk between PGE(2)/EP(1)R and ROS signaling in the SFO is required for Ang II HTN. Radiotelemetric assessment of blood pressure revealed that HTN induced by infusion of systemic "slow-pressor" doses of Ang II was abolished in mice with null mutations in EP(1)R or COX-1 but not COX-2. Slow-pressor Ang II-evoked HTN and ROS formation in the SFO were prevented when the EP(1)R antagonist SC-51089 was infused directly into brains of wild-type mice, and Ang-II-induced ROS production was blunted in cells dissociated from SFO of EP(1)R(-/-) and COX-1(-/-) but not COX-2(-/-) mice. In addition, slow-pressor Ang II infusion caused a ≈3-fold increase in PGE(2) levels in the SFO but not in other brain regions. Finally, genetic reconstitution of EP(1)R selectively in the SFO of EP(1)R-null mice was sufficient to rescue slow-pressor Ang II-elicited HTN and ROS formation in the SFO of this model. Thus, COX 1-derived PGE(2) signaling through EP(1)R in the SFO is required for the ROS-mediated HTN induced by systemic infusion of Ang II and suggests that EP(1)R in the SFO may provide a novel target for antihypertensive therapy.

  13. A novel synthetic Asiatic acid derivative induces apoptosis and inhibits proliferation and mobility of gastric cancer cells by suppressing STAT3 signaling pathway

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    Wang G

    2016-12-01

    Full Text Available Gang Wang,1 Yue Jing,2 Lingsen Cao,3 Changchang Gong,1 Zhunan Gong,1,3 Xiangrong Cao3 1Center for New Drug Research and Development, College of Life Science, Nanjing Normal University, 2Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical School of Nanjing University, 3Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, People’s Republic of China Abstract: Activation of the transcription factor, signal transducers and activators of transcription 3 (STAT3, has been linked to the proliferation and migration of a variety of human cancer cells. These actions occur via the upregulation or downregulation of cell survival and tumor suppressor genes, respectively. Importantly, agents that can suppress STAT3 activation have the potential for use in the prevention and treatment of various cancers. In this study, an Asiatic acid (AA derivative, N-(2α,3β,23-acetoxyurs-12-en-28-oyl-L-proline methyl ester (AA-PMe, is reported to dose dependently suppress constitutive STAT3 activation in gastric cancer cells. This inhibition was mediated by blockade of Janus-activated kinase 2. Additionally, AA-PMe regulated the expression of STAT3-modulated gene products, including cyclin D1, Bax, Bcl-2, c-Myc, and matrix metalloproteinase (MMP-2 and MMP-9. Finally, transfection with both a STAT3 mimic and an inhibitor reversed the AA-PMe-driven modulation of STAT3 downstream gene products. Overall, these results suggest that AA-PMe is a novel blocker of STAT3 activation and has the potential for the prevention and treatment of gastric cancer. Keywords: gastric cancer, signal transducer and activator of transcription 3, Asiatic acid derivative, cell cycle, apoptosis, invasion

  14. Allicin induces the upregulation of ABCA1 expression via PPARγ/LXRα signaling in THP-1 macrophage-derived foam cells.

    Science.gov (United States)

    Lin, Xiao-Long; Hu, Hui-Jun; Liu, Yuan-Bo; Hu, Xue-Mei; Fan, Xiao-Juan; Zou, Wei-Wen; Pan, Yong-Quan; Zhou, Wen-Quan; Peng, Min-Wen; Gu, Cai-Hong

    2017-06-01

    Allicin is considered anti-atherosclerotic due to its antioxidant and anti-inflammatory effects, which makes it an important drug for the prevention and treatment of atherosclerosis. However, the effects of allicin on foam cells are unclear. Thus, in this study, we examined the effects of allicin on lipid accumulation via peroxisome proliferator-activated receptor γ (PPARγ)/liver X receptor α (LXRα) in THP‑1 macrophage-derived foam cells. THP‑1 cells were exposed to 100 nM phorbol myristate acetate (PMA) for 24 h, and then to oxydized low-density lipoprotein (ox-LDL; 50 mg/ml) to induce foam cell formation. The results of Oil Red O staining and high-performance liquid chromatography (HPLC) revealed showed that pre-treatment of the foam cells with allicin decreased total cholesterol, free cholesterol (FC) and cholesterol ester levels in cells, and also decreased lipid accumulation. Moreover, allicin upregulated ATP binding cassette transporter A1 (ABCA1) expression and promoted cholesterol efflux. However, these effects were significantly abolished by transfection with siRNA targeting ABCA1. Furthermore, PPARγ/LXRα signaling was activated by allicin treatment. The allicin-induced upregulation of ABCA1 expression was also abolished by PPARγ inhibitor (GW9662) and siRNA or LXRα siRNA co-treatment. Overall, our data demonstrate that the allicin-induced upregulation of ABCA1 promotes cholesterol efflux and reduces lipid accumulation via PPARγ/LXRα signaling in THP‑1 macrophage-derived foam cells.

  15. Low-Intensity Extracorporeal Shock Wave Therapy Enhances Brain-Derived Neurotrophic Factor Expression through PERK/ATF4 Signaling Pathway

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    Bohan Wang

    2017-02-01

    Full Text Available Low-intensity extracorporeal shock wave therapy (Li-ESWT is used in the treatment of erectile dysfunction, but its mechanisms are not well understood. Previously, we found that Li-ESWT increased the expression of brain-derived neurotrophic factor (BDNF. Here we assessed the underlying signaling pathways in Schwann cells in vitro and in penis tissue in vivo after nerve injury. The result indicated that BDNF were significantly increased by the Li-ESWT after nerve injury, as well as the expression of BDNF in Schwann cells (SCs, RT4-D6P2T in vitro. Li-ESWT activated the protein kinase RNA-like endoplasmic reticulum (ER kinase (PERK pathway by increasing the phosphorylation levels of PERK and eukaryotic initiation factor 2a (eIF2α, and enhanced activating transcription factor 4 (ATF4 in an energy-dependent manner. In addition, GSK2656157—an inhibitor of PERK—effectively inhibited the effect of Li-ESWT on the phosphorylation of PERK, eIF2α, and the expression of ATF4. Furthermore, silencing ATF4 dramatically attenuated the effect of Li-ESWT on the expression of BDNF, but had no effect on hypoxia-inducible factor (HIF1α or glial cell-derived neurotrophic factor (GDNF in Schwann cells. In conclusion, our findings shed new light on the underlying mechanisms by which Li-ESWT may stimulate the expression of BDNF through activation of PERK/ATF4 signaling pathway. This information may help to refine the use of Li-ESWT to further improve its clinical efficacy.

  16. Blockade of TLR9 signaling in B cells impaired anti-dsDNA antibody production in mice induced by activated syngenic lymphocyte-derived DNA immunization.

    Science.gov (United States)

    Chen, Min; Zhang, Weijuan; Xu, Wei; Zhang, Feng; Xiong, Sidong

    2011-07-01

    We previously established a systemic lupus erythematosus (SLE) animal model in non-susceptible BALB/c mice by immunizing with activated syngeneic lymphocyte-derived DNA (ALD-DNA), manifested by high level of anti-double-stranded DNA (dsDNA) antibodies (Abs), proteinuria, glomerular deposition of immune complex and glomerulonephritis. The production of anti-dsDNA Abs is closely related with the renal inflammation and damage in this model. However, recognition of ALD-DNA and its signaling pathway within antigen-presenting cells (APC) remains not fully clarified. Herein, in this study, Toll-like receptor 9 (TLR9), a well-known pattern-recognition receptor for dsDNA with CpG motif, was found to be dynamically up-regulated in B cells during the process of the SLE disease. Knockdown of TLR9 by short interfering RNA (siRNA) in B cells in vitro and in vivo reduced the production of anti-dsDNA antibody and consequently ameliorated the SLE syndrome in mice while the affinity and isotype of the antibody remained the same. Our results implied that TLR9 signaling of B cells might play an important role in the production of anti-dsDNA Abs triggered by auto dsDNA, which would extend our understanding of TLR9 immune recognition in the pathogenesis of SLE disease. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Degenerative Suspensory Ligament Desmitis (DSLD in Peruvian Paso Horses Is Characterized by Altered Expression of TGFβ Signaling Components in Adipose-Derived Stromal Fibroblasts.

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    Wei Luo

    Full Text Available Equine degenerative suspensory ligament desmitis (DSLD in Peruvian Paso horses typically presents at 7-15 years and is characterized by lameness, focal disorganization of collagen fibrils, and chondroid deposition in the body of the ligament. With the aim of developing a test for disease risk (that can be used to screen horses before breeding we have quantified the expression of 76 TGFβ-signaling target genes in adipose-derived stromal fibroblasts (ADSCs from six DSLD-affected and five unaffected Paso horses. Remarkably, 35 of the genes showed lower expression (p<0.05 in cells from DSLD-affected animals and this differential was largely eliminated by addition of exogenous TGFβ1. Moreover, TGFβ1-mediated effects on expression were prevented by the TGFβR1/2 inhibitor LY2109761, showing that the signaling was via a TGFβR1/2 complex. The genes affected by the pathology indicate that it is associated with a generalized metabolic disturbance, since some of those most markedly altered in DSLD cells (ATF3, MAPK14, ACVRL1 (ALK1, SMAD6, FOS, CREBBP, NFKBIA, and TGFBR2 represent master-regulators in a wide range of cellular metabolic responses.

  18. Osteitis fibrosa is mediated by Platelet-Derived Growth Factor-A via a phosphoinositide 3-kinase-dependent signaling pathway in a rat model for chronic hyperparathyroidism.

    Science.gov (United States)

    Lowry, Malcolm B; Lotinun, Sutada; Leontovich, Alexey A; Zhang, Minzhi; Maran, Avudaiappan; Shogren, Kristen L; Palama, Brett K; Marley, Kevin; Iwaniec, Urszula T; Turner, Russell T

    2008-11-01

    Abnormal secretion of PTH by the parathyroid glands contributes to a variety of common skeletal disorders. Prior studies implicate platelet-derived growth factor-A (PDGF-A) as an important mediator of selective PTH actions on bone. The present studies used targeted gene profiling and small-molecule antagonists directed against candidate gene products to elucidate the roles of specific PTH-regulated genes and signaling pathways. A group of 29 genes in rats continuously infused with PTH and cotreated with the PDGF receptor antagonist trapidil were differentially expressed compared with PTH treatment alone. Several of the identified genes were functionally clustered as regulators of fibroblast differentiation and extracellular matrix modeling, including the matrix cross-linking enzyme lysyl oxidase (LOX). Treatment with beta-aminopropionitrile, an irreversible inhibitor of LOX activity, dramatically reduced diffuse mineralization but had no effect on PTH-induced fibrosis. In contrast, the receptor tyrosine kinase inhibitor Gleevec and the phosphoinositide 3-kinase inhibitor wortmannin each reduced bone marrow fibrosis. In summary, the present studies support the hypotheses that PTH-induced bone marrow fibrosis is mediated by PDGF-A via a phosphoinositide 3-kinase-dependent signaling pathway and that increased LOX gene expression plays a key role in abnormal mineralization, a hallmark of chronic hyperparathyroidism.

  19. Ropinirole and Pramipexole Promote Structural Plasticity in Human iPSC-Derived Dopaminergic Neurons via BDNF and mTOR Signaling

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    Ginetta Collo

    2018-01-01

    Full Text Available The antiparkinsonian ropinirole and pramipexole are D3 receptor- (D3R- preferring dopaminergic (DA agonists used as adjunctive therapeutics for the treatment resistant depression (TRD. While the exact antidepressant mechanism of action remains uncertain, a role for D3R in the restoration of impaired neuroplasticity occurring in TRD has been proposed. Since D3R agonists are highly expressed on DA neurons in humans, we studied the effect of ropinirole and pramipexole on structural plasticity using a translational model of human-inducible pluripotent stem cells (hiPSCs. Two hiPSC clones from healthy donors were differentiated into midbrain DA neurons. Ropinirole and pramipexole produced dose-dependent increases of dendritic arborization and soma size after 3 days of culture, effects antagonized by the selective D3R antagonists SB277011-A and S33084 and by the mTOR pathway kinase inhibitors LY294002 and rapamycin. All treatments were also effective in attenuating the D3R-dependent increase of p70S6-kinase phosphorylation. Immunoneutralisation of BDNF, inhibition of TrkB receptors, and blockade of MEK-ERK signaling likewise prevented ropinirole-induced structural plasticity, suggesting a critical interaction between BDNF and D3R signaling pathways. The highly similar profiles of data acquired with DA neurons derived from two hiPSC clones underpin their reliability for characterization of pharmacological agents acting via dopaminergic mechanisms.

  20. Wnt16 Signaling Is Required for IL-1β-Induced Matrix Metalloproteinase-13-Regulated Proliferation of Human Stem Cell-Derived Osteoblastic Cells

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    Nobuaki Ozeki

    2016-02-01

    Full Text Available We established a differentiation method for homogeneous α7 integrin-positive human skeletal muscle stem cell (α7+hSMSC-derived osteoblast-like (α7+hSMSC-OB cells, and found that interleukin (IL-1β induces matrix metalloproteinase (MMP-13-regulated proliferation of these cells. These data suggest that MMP-13 plays a potentially unique physiological role in the regeneration of osteoblast-like cells. Here, we examined whether up-regulation of MMP-13 activity by IL-1β was mediated by Wingless/int1 (Wnt signaling and increased the proliferation of osteoblast-like cells. IL-1β increased the mRNA and protein levels of Wnt16 and the Wnt receptor Lrp5/Fzd2. Exogenous Wnt16 was found to increase MMP-13 mRNA, protein and activity, and interestingly, the proliferation rate of these cells. Treatment with small interfering RNAs against Wnt16 and Lrp5 suppressed the IL-1β-induced increase in cell proliferation. We revealed that a unique signaling cascade IL-1β→Wnt16→Lrp5→MMP-13, was intimately involved in the proliferation of osteoblast-like cells, and suggest that IL-1β-induced MMP-13 expression and changes in cell proliferation are regulated by Wnt16.

  1. Calcium Supplement Derived from Gallus gallus domesticus Promotes BMP-2/RUNX2/SMAD5 and Suppresses TRAP/RANK Expression through MAPK Signaling Activation

    Directory of Open Access Journals (Sweden)

    Han Seok Yoo

    2017-05-01

    Full Text Available The present study evaluated the effects of a calcium (Ca supplement derived from Gallus gallus domesticus (GD on breaking force, microarchitecture, osteogenic differentiation and osteoclast differentiation factor expression in vivo in Ca-deficient ovariectomized (OVX rats. One percent of Ca supplement significantly improved Ca content and bone strength of the tibia. In micro-computed tomography analysis, 1% Ca supplement attenuated OVX- and low Ca-associated changes in bone mineral density, trabecular thickness, spacing and number. Moreover, 1% Ca-supplemented diet increased the expression of osteoblast differentiation marker genes, such as bone morphogenetic protein-2, Wnt3a, small mothers against decapentaplegic 1/5/8, runt-related transcription factor 2, osteocalcin and collagenase-1, while it decreased the expression of osteoclast differentiation genes, such as thrombospondin-related anonymous protein, cathepsin K and receptor activator of nuclear factor kappa B. Furthermore, 1% Ca-supplemented diet increased the levels of phosphorylated extracellular signal-regulated kinase and c-Jun N-terminal kinase. The increased expression of osteoblast differentiation marker genes and activation of mitogen-activated protein kinase signaling were associated with significant increases in trabecular bone volume, which plays an important role in the overall skeletal strength. Our results demonstrated that 1% Ca supplement inhibited osteoclastogenesis, stimulated osteoblastogenesis and restored bone loss in OVX rats.

  2. High-speed image analysis reveals chaotic vibratory behaviors of pathological vocal folds

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Yu, E-mail: yuzhang@xmu.edu.c [Key Laboratory of Underwater Acoustic Communication and Marine Information Technology of the Ministry of Education, Xiamen University, Xiamen Fujian 361005 (China); Shao Jun [Shanghai EENT Hospital of Fudan University, Shanghai (China); Krausert, Christopher R. [Department of Surgery, Division of Otolaryngology - Head and Neck Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792-7375 (United States); Zhang Sai [Key Laboratory of Underwater Acoustic Communication and Marine Information Technology of the Ministry of Education, Xiamen University, Xiamen Fujian 361005 (China); Jiang, Jack J. [Shanghai EENT Hospital of Fudan University, Shanghai (China); Department of Surgery, Division of Otolaryngology - Head and Neck Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792-7375 (United States)

    2011-01-15

    Research highlights: Low-dimensional human glottal area data. Evidence of chaos in human laryngeal activity from high-speed digital imaging. Traditional perturbation analysis should be cautiously applied to aperiodic high speed image signals. Nonlinear dynamic analysis may be helpful for understanding disordered behaviors in pathological laryngeal systems. - Abstract: Laryngeal pathology is usually associated with irregular dynamics of laryngeal activity. High-speed imaging facilitates direct observation and measurement of vocal fold vibrations. However, chaotic dynamic characteristics of aperiodic high-speed image data have not yet been investigated in previous studies. In this paper, we will apply nonlinear dynamic analysis and traditional perturbation methods to quantify high-speed image data from normal subjects and patients with various laryngeal pathologies including vocal fold nodules, polyps, bleeding, and polypoid degeneration. The results reveal the low-dimensional dynamic characteristics of human glottal area data. In comparison to periodic glottal area series from a normal subject, aperiodic glottal area series from pathological subjects show complex reconstructed phase space, fractal dimension, and positive Lyapunov exponents. The estimated positive Lyapunov exponents provide the direct evidence of chaos in pathological human vocal folds from high-speed digital imaging. Furthermore, significant differences between the normal and pathological groups are investigated for nonlinear dynamic and perturbation analyses. Jitter in the pathological group is significantly higher than in the normal group, but shimmer does not show such a difference. This finding suggests that the traditional perturbation analysis should be cautiously applied to high speed image signals. However, the correlation dimension and the maximal Lyapunov exponent reveal a statistically significant difference between normal and pathological groups. Nonlinear dynamic analysis is capable of

  3. The guggulsterone derivative GG-52 inhibits NF-κB signaling in gastric epithelial cells and ameliorates ethanol-induced gastric mucosal lesions in mice.

    Science.gov (United States)

    Kim, Jung Mogg; Kim, Su Hyun; Ko, Su Hyuk; Jung, Jireh; Chun, Jaeyoung; Kim, Nayoung; Jung, Hyun Chae; Kim, Joo Sung

    2013-01-15

    Gastric mucosal inflammation can develop after challenge with noxious stimuli such as alcohol. Specially, alcohol stimulates the release of inflammatory cytokines but does not increase gastric acid secretion, leading to gastric mucosal damage. The plant sterol guggulsterone and its novel derivative GG-52 have been reported to inhibit nuclear factor-κB (NF-κB) signaling in intestinal epithelial cells and experimental colitis. In the present study, we investigated the anti-inflammatory effects of GG-52 on gastric epithelial cells and on ethanol-induced gastric mucosal inflammation in mice. GG-52 inhibited the expression of interleukin-8 (IL-8) in gastric epithelial AGS and MKN-45 cell lines stimulated with tumor necrosis factor (TNF)-α in a dose-dependent manner. Pretreatment with GG-52 suppressed TNF-α-induced activation of IκB kinase (IKK) and NF-κB signaling in MKN-45 cells. In contrast, the inactive analog GG-46 did not produce significant changes in IL-8 expression or NF-κB activation. In a model of ethanol-induced murine gastritis, administration of GG-52 significantly reduced the severity of gastritis, as assessed by macroscopic and histological evaluation of gastric mucosal damage. In addition, the ethanol-induced upregulation of chemokine KC, a mouse homolog of IL-8, and phosphorylated p65 NF-κB signals were significantly inhibited in murine gastric mucosa pretreated with GG-52. These results indicate that GG-52 suppresses NF-κB activation in gastric epithelial cells and ameliorates ethanol-induced gastric mucosal lesions in mice, suggesting that GG-52 may be a potential gastroprotective agent.

  4. Object speed derived from the integration of motion in the image plane and motion-in-depth signaled by stereomotion and looming.

    Science.gov (United States)

    Khuu, Sieu K; Lee, Terence C P; Hayes, Anthony

    2010-04-21

    We investigate the influence of local motion in the retinal image plane on the perception of speed-in-depth. Observers judged the apparent speed-in-depth of a square plane of dynamic dots that moved towards the observer. Dots forming the surface of the plane underwent random-direction motion in the image plane. We examined the consequences of changing the dots' image-plane speed on the apparent speed of the stimulus as it traversed depth, where depth is signaled by stereomotion or looming. Results for both the stereomotion and looming conditions indicate that as the speed of random-direction motion in the image plane increases, the apparent speed-in-depth of the stimulus also increases. When stereomotion was used to signal motion-in-depth, the speed judgment is adequately modeled by the resultant of a vector sum of dot-speed in the image plane and speed-in-depth. However, when looming was used to define motion-in-depth, a different pattern of results was found - the apparent speed-in-depth is lower than the actual speed-in-depth, and the results are best predicted by simple averaging. Our results demonstrate that the integration of speed in the image plane and speed-in-depth, to determine object speed, is dependent on the type of cue used to signal motion-in-depth, and this difference is a consequence of the ways in which looming and stereomotion cue motion-in-depth. Looming is derived not at a local stage of motion analysis, but is available only via global integration of local velocities, and consequently global speed conforms to the average speed. Stereomotion, on the other hand, provides an effective cue for individuating local velocities in depth. Copyright 2010 Elsevier Ltd. All rights reserved.

  5. Decreased nuclear stiffness via FAK-ERK1/2 signaling is necessary for osteopontin-promoted migration of bone marrow-derived mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Lingling, E-mail: liulingling2012@163.com [Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Luo, Qing, E-mail: qing.luo@cqu.edu.cn [Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Sun, Jinghui, E-mail: sunjhemail@163.com [Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Wang, Aoli, E-mail: leaf13332@163.com [Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Shi, Yisong, E-mail: shiyis@cqu.edu.cn [Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Ju, Yang, E-mail: ju@mech.nagoya-u.ac.jp [Department of Mechanical Science and Engineering, Nagoya University, Nagoya 464-8603 (Japan); Morita, Yasuyuki, E-mail: morita@mech.nagoya-u.ac.jp [Department of Mechanical Science and Engineering, Nagoya University, Nagoya 464-8603 (Japan); Song, Guanbin, E-mail: song@cqu.edu.cn [Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China)

    2017-06-15

    Migration of bone marrow-derived mesenchymal stem cells (BMSCs) plays an important role in many physiological and pathological settings, including wound healing. During the migration of BMSCs through interstitial tissues, the movement of the nucleus must be coordinated with the cytoskeletal dynamics, which in turn affects the cell migration efficiency. Our previous study indicated that osteopontin (OPN) significantly promotes the migration of rat BMSCs. However, the nuclear behaviors and involved molecular mechanisms in OPN-mediated BMSC migration are largely unclear. In the present study, using an atomic force microscope (AFM), we found that OPN could decrease the nuclear stiffness of BMSCs and reduce the expression of lamin A/C, which is the main determinant of nuclear stiffness. Increased lamin A/C expression attenuates BMSC migration by increasing nuclear stiffness. Decreased lamin A/C expression promotes BMSC migration by decreasing nuclear stiffness. Furthermore, OPN promotes BMSC migration by diminishing lamin A/C expression and decreasing nuclear stiffness via the FAK-ERK1/2 signaling pathway. This study provides strong evidence for the role of nuclear mechanics in BMSC migration as well as new insight into the molecular mechanisms of OPN-promoted BMSC migration. - Highlights: • OPN promotes BMSC migration by decreasing nuclear stiffness. • Lamin A/C knockdown decreases, while its overexpression enhances, the nuclear stiffness of BMSCs. • Lamin A/C overexpression and downregulation affect the migration of BMSCs. • OPN diminishes lamin A/C expression and decreases nuclear stiffness through the activation of the FAK-ERK1/2 signaling pathway. • OPN promotes BMSC migration via the FAK-ERK1/2 signaling pathway.

  6. Sphingosine-1-phosphate/S1P Receptors Signaling Modulates Cell Migration in Human Bone Marrow-Derived Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Yaxian Kong

    2014-01-01

    Full Text Available The recruitment of bone marrow-derived mesenchymal stem cells (BMSCs to damaged tissues and sites of inflammation is an essential step for clinical therapy. However, the signals regulating the motility of these cells are still not fully understood. Sphingosine-1-phosphate (S1P, a bioactive sphingolipid metabolite, is known to have a variety of biological effects on various cells. Here, we investigated the roles of S1P and S1P receptors (S1PRs in migration of human BMSCs. We found that S1P exerted a powerful migratory action on human BMSCs. Moreover, by employing RNA interference technology and pharmacological tools, we demonstrated that S1PR1 and S1PR3 are responsible for S1P-induced migration of human BMSCs. In contrast, S1PR2 mediates the inhibition of migration. Additionally, we explored the downstream signaling pathway of the S1P/S1PRs axis and found that activation of S1PR1 or S1PR3 increased migration of human BMSCs through a Gi/extracellular regulated protein kinases 1/2- (ERK1/2- dependent pathway, whereas activation of S1PR2 decreased migration through the Rho/Rho-associated protein kinase (ROCK pathway. In conclusion, we reveal that the S1P/S1PRs signaling axis regulates the migration of human BMSCs via a dual-directional mechanism. Thus, selective modulation of S1PR’s activity on human BMSCs may provide an effective approach to immunotherapy or tissue regeneration.

  7. A novel synthetic derivative of melatonin, 5-hydroxy-2’-isobutyl-streptochlorin (HIS), inhibits inflammatory responses via regulation of TRIF-dependent signaling and inflammasome activation

    Energy Technology Data Exchange (ETDEWEB)

    Shim, Do-Wan [Department of Biotechnology, Research Institute of Inflammatory Disease, Konkuk University, Chungju (Korea, Republic of); Shin, Hee Jae [Marine Natural Products Chemistry Laboratory, Korea Institute of Ocean Science & Technology, Ansan (Korea, Republic of); Han, Ji-Won; Ji, Young-Eun; Jang, Cheol-Hun; Koppula, Sushruta; Kang, Tae-Bong [Department of Biotechnology, Research Institute of Inflammatory Disease, Konkuk University, Chungju (Korea, Republic of); Lee, Kwang-Ho, E-mail: kwangho@kku.ac.kr [Department of Biotechnology, Research Institute of Inflammatory Disease, Konkuk University, Chungju (Korea, Republic of)

    2015-04-15

    Melatonin is substantially reported to possess anti-inflammatory properties. In the present study, we synthesized a novel melatonin derivative, 5-hydroxy-2′-isobutyl-streptochlorin (HIS), which displayed superior anti-inflammatory properties to its parent compound. Further, we explored its underlying mechanisms in cellular and experimental animal models. Lipopolysaccharide was used to induce in vitro inflammatory responses in RAW 264.7 macrophages. LPS-primed macrophages were pulsed with biologically unrelated toxic molecules to evaluate the role of HIS on inflammasome activation. In vivo verifications were carried out using acute lung injury (ALI) and Escherichia coli-induced septic shock mouse models. HIS inhibited the production of proinflammatory mediators and cytokines such as nitric oxide, cyclooxygenase 2, IL-1β, IL-6 and TNF-α in LPS-stimulated RAW 264.7 macrophages. HIS suppressed the infiltration of immune cells into the lung and the production of pro-inflammatory cytokines such as IL-6 and TNF-α in broncho-alveolar lavage fluid in the ALI mouse model. Mechanistic studies revealed that the inhibitory effects of HIS were mediated through the regulation of the TIR domain-containing, adaptor-inducing, interferon-β (TRIF)-dependent signaling pathway from toll-like receptors. Further, HIS attenuated IL-1β secretion via the inhibition of NLRP3 inflammasome activation independent of mitochondrial ROS production. Furthermore, HIS suppressed IL-1β, IL-6 and interferon-β production in peritoneal lavage in the Escherichia coli-induced sepsis mouse model. In conclusion, HIS exerted potent anti-inflammatory effects via the regulation of TRIF-dependent signaling and inflammasome activation. Notably, the superior anti-inflammatory properties of this derivative compared with its parent compound could be a promising lead for treating various inflammatory-mediated diseases. - Highlights: • Νovel compound, 5-hydroxy-2′-isobutyl-streptochlorin (HIS) was

  8. TNF-TNFR2/p75 signaling inhibits early and increases delayed nontargeted effects in bone marrow-derived endothelial progenitor cells.

    Science.gov (United States)

    Sasi, Sharath P; Song, Jin; Park, Daniel; Enderling, Heiko; McDonald, J Tyson; Gee, Hannah; Garrity, Brittany; Shtifman, Alexander; Yan, Xinhua; Walsh, Kenneth; Natarajan, Mohan; Kishore, Raj; Goukassian, David A

    2014-05-16

    TNF-α, a pro-inflammatory cytokine, is highly expressed after being irradiated (IR) and is implicated in mediating radiobiological bystander responses (RBRs). Little is known about specific TNF receptors in regulating TNF-induced RBR in bone marrow-derived endothelial progenitor cells (BM-EPCs). Full body γ-IR WT BM-EPCs showed a biphasic response: slow decay of p-H2AX foci during the initial 24 h and increase between 24 h and 7 days post-IR, indicating a significant RBR in BM-EPCs in vivo. Individual TNF receptor (TNFR) signaling in RBR was evaluated in BM-EPCs from WT, TNFR1/p55KO, and TNFR2/p75KO mice, in vitro. Compared with WT, early RBR (1-5 h) were inhibited in p55KO and p75KO EPCs, whereas delayed RBR (3-5 days) were amplified in p55KO EPCs, suggesting a possible role for TNFR2/p75 signaling in delayed RBR. Neutralizing TNF in γ-IR conditioned media (CM) of WT and p55KO BM-EPCs largely abolished RBR in both cell types. ELISA protein profiling of WT and p55KO EPC γ-IR-CM over 5 days showed significant increases in several pro-inflammatory cytokines, including TNF-α, IL-1α (Interleukin-1 alpha), RANTES (regulated on activation, normal T cell expressed and secreted), and MCP-1. In vitro treatments with murine recombinant (rm) TNF-α and rmIL-1α, but not rmMCP-1 or rmRANTES, increased the formation of p-H2AX foci in nonirradiated p55KO EPCs. We conclude that TNF-TNFR2 signaling may induce RBR in naïve BM-EPCs and that blocking TNF-TNFR2 signaling may prevent delayed RBR in BM-EPCs, conceivably, in bone marrow milieu in general. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Brain-derived neurotrophic factor (BDNF)-induced tropomyosin-related kinase B (Trk B) signaling is a potential therapeutic target for peritoneal carcinomatosis arising from colorectal cancer.

    Science.gov (United States)

    Tanaka, Koji; Okugawa, Yoshinaga; Toiyama, Yuji; Inoue, Yasuhiro; Saigusa, Susumu; Kawamura, Mikio; Araki, Toshimitsu; Uchida, Keiichi; Mohri, Yasuhiko; Kusunoki, Masato

    2014-01-01

    Tropomyosin-related receptor kinase B (TrkB) signaling, stimulated by brain-derived neurotrophic factor (BDNF) ligand, promotes tumor progression, and is related to the poor prognosis of various malignancies. We sought to examine the clinical relevance of BDNF/TrkB expression in colorectal cancer (CRC) tissues, its prognostic value for CRC patients, and its therapeutic potential in vitro and in vivo. Two hundred and twenty-three CRC patient specimens were used to determine both BDNF and TrkB mRNA levels. The expression of these proteins in their primary and metastatic tumors was investigated by immunohistochemistry. CRC cell lines and recombinant BDNF and K252a (a selective pharmacological pan-Trk inhibitor) were used for in vitro cell viability, migration, invasion, anoikis resistance and in vivo peritoneal metastasis assays. Tissue BDNF mRNA was associated with liver and peritoneal metastasis. Tissue TrkB mRNA was also associated with lymph node metastasis. The co-expression of BDNF and TrkB was associated with liver and peritoneal metastasis. Patients with higher BDNF, TrkB, and co-expression of BDNF and TrkB had a significantly poor prognosis. BDNF increased tumor cell viability, migration, invasion and inhibited anoikis in the TrkB-expressing CRC cell lines. These effects were suppressed by K252a. In mice injected with DLD1 co-expressing BDNF and TrkB, and subsequently treated with K252a, peritoneal metastatic nodules was found to be reduced, as compared with control mice. BDNF/TrkB signaling may thus be a potential target for treating peritoneal carcinomatosis arising from colorectal cancer.

  10. IGF-1 promotes angiogenesis in endothelial cells/adipose-derived stem cells co-culture system with activation of PI3K/Akt signal pathway.

    Science.gov (United States)

    Lin, Shiyu; Zhang, Qi; Shao, Xiaoru; Zhang, Tao; Xue, Changyue; Shi, Sirong; Zhao, Dan; Lin, Yunfeng

    2017-12-01

    The aim of this study was to investigate the role of insulin-like growth factor-1 (IGF-1) and crosstalk between endothelial cells (ECs) and adipose-derived stem cells (ASCs) in the process of angiogenesis. A three-dimensional collagen gel used to culture mouse ASCs and mouse ECs in vitro was established. The effects of angiogenesis after exposure to IGF-1 were observed by confocal laser scanning microscopy. Western blotting and qPCR were performed to elucidate the underlying mechanisms. IGF-1 treatment promoted the formation of vessel-like structures and the recruitment of ASCs in the three-dimensional collagen gel. The angiogenic genes and proteins in ECs were up-regulated by IGF-1 and in co-culture. Similar changes in the genes and in the proteins were detected in ASCs after exposure to IGF-1 and co-culture. p-Akt expression levels were high in ECs and ASCs after exposure to IGF-1 and co-culture. IGF-1 and co-culture between cells facilitate the process of angiogenesis via the PI3-kinase/Akt signalling pathway. In ECs, IGF-1 stimulates the expression of angiogenesis-related growth factors with the activation of the PI3-kinase/Akt signalling pathway. Co-cultured ECs exposed to excess VEGF-A and other angiogenesis-related growth factors para-secreted from ASCs exhibit high expression of angiogenesis-related genes and proteins. In ASCs, IGF-1 induces the recruitment and function of ASCs by up-regulating the expression of PDGFB, MMPs and α-SMA. Crosstalk with ECs further facilitates changes in ASCs. © 2017 John Wiley & Sons Ltd.

  11. A Naturally-Derived Small Molecule Disrupts Ligand-Dependent and Ligand-Independent Androgen Receptor Signaling in Human Prostate Cancer Cells

    Science.gov (United States)

    Amin, Karishma S.; Jagadeesh, Shankar; Baishya, Gakul; Rao, Paruchuri G.; Barua, Nabin C.; Bhattacharya, Samir; Banerjee, Partha P.

    2014-01-01

    Continued reliance on androgen receptor (AR) signaling is a hallmark of prostate cancer, including the development of castration-resistant prostate cancer (CRPC), making it an attractive therapeutic target for prostate cancer treatment. Mahanine is a novel carbazole alkaloid derived from the leaves of Murraya koenigii, commonly known as the curry leaf plant, which grows widely across East Asia. We show here that mahanine possesses the ability to inhibit ligand-dependent and ligand-independent AR transactivation, leading to a prominent decline in AR target gene expression. Mahanine treatment causes a time- and dose- dependent decline in AR protein levels, including truncated AR splice variants, in a panel of androgen-responsive and androgen-independent prostate cancer cells. The decrease in AR levels induced by mahanine occurs post-translationally by proteasomal degradation, without any change in AR gene expression. Mahanine treatment induces an outward movement of the AR from the nucleus to the cytoplasm, leading to an initial rise in cytoplasmic AR levels, followed by a gradual decline in the AR levels in both cellular compartments. Ligand-induced AR phosphorylation at Ser-81, a phospho-site associated with prostate cancer cell growth and AR transactivity, is greatly diminished in the presence of mahanine. The decline in AR phosphorylation at Ser-81 by mahanine occurs via the inactivation of mitotic kinase, CDK1. Collectively, our data demonstrate that mahanine strongly disrupts androgen receptor signaling and inhibits the growth of androgen-dependent and –independent prostate cancer cells, thereby implicating a therapeutic role for mahanine in prostate cancer treatment. PMID:24258347

  12. Wnt3a upregulates brain-derived insulin by increasing NeuroD1 via Wnt/β-catenin signaling in the hypothalamus.

    Science.gov (United States)

    Lee, Jaemeun; Kim, Kyungchan; Yu, Seong-Woon; Kim, Eun-Kyoung

    2016-03-08

    Insulin plays diverse roles in the brain. Although insulin produced by pancreatic β-cells that crosses the blood-brain barrier is a major source of brain insulin, recent studies suggest that insulin is also produced locally within the brain. However, the mechanisms underlying the production of brain-derived insulin (BDI) are not yet known. Here, we examined the effect of Wnt3a on BDI production in a hypothalamic cell line and hypothalamic tissue. In N39 hypothalamic cells, Wnt3a treatment significantly increased the expression of the Ins2 gene, which encodes the insulin isoform predominant in the mouse brain, by activating Wnt/β-catenin signaling. The concentration of insulin was higher in culture medium of Wnt3a-treated cells than in that of untreated cells. Interestingly, neurogenic differentiation 1 (NeuroD1), a target of Wnt/β-catenin signaling and one of transcription factors for insulin, was also induced by Wnt3a treatment in a time- and dose-dependent manner. In addition, the treatment of BIO, a GSK3 inhibitor, also increased the expression of Ins2 and NeuroD1. Knockdown of NeuroD1 by lentiviral shRNAs reduced the basal expression of Ins2 and suppressed Wnt3a-induced Ins2 expression. To confirm the Wnt3a-induced increase in Ins2 expression in vivo, Wnt3a was injected into the hypothalamus of mice. Wnt3a increased the expression of NeuroD1 and Ins2 in the hypothalamus in a manner similar to that observed in vitro. Taken together, these results suggest that BDI production is regulated by the Wnt/β-catenin/NeuroD1 pathway in the hypothalamus. Our findings will help to unravel the regulation of BDI production in the hypothalamus.

  13. Impact of extracellular matrix derived from osteoarthritis subchondral bone osteoblasts on osteocytes: role of integrinβ1 and focal adhesion kinase signaling cues

    Science.gov (United States)

    2013-01-01

    Introduction Our recent study indicated that subchondral bone pathogenesis in osteoarthritis (OA) is associated with osteocyte morphology and phenotypic abnormalities. However, the mechanism underlying this abnormality needs to be identified. In this study we investigated the effect of extracellular matrix (ECM) produced from normal and OA bone on osteocytic cells function. Methods De-cellularized matrices, resembling the bone provisional ECM secreted from primary human subchondral bone osteoblasts (SBOs) of normal and OA patients were used as a model to study the effect on osteocytic cells. Osteocytic cells (MLOY4 osteocyte cell line) cultured on normal and OA derived ECMs were analyzed by confocal microscopy, scanning electron microscopy (SEM), cell attachment assays, zymography, apoptosis assays, qRT-PCR and western blotting. The role of integrinβ1 and focal adhesion kinase (FAK) signaling pathways during these interactions were monitored using appropriate blocking antibodies. Results The ECM produced by OA SBOs contained less mineral content, showed altered organization of matrix proteins and matrix structure compared with the matrices produced by normal SBOs. Culture of osteocytic cells on these defective OA ECM resulted in a decrease of integrinβ1 expression and the de-activation of FAK cell signaling pathway, which subsequently affected the initial osteocytic cell’s attachment and functions including morphological abnormalities of cytoskeletal structures, focal adhesions, increased apoptosis, altered osteocyte specific gene expression and increased Matrix metalloproteinases (MMP-2) and -9 expression. Conclusion This study provides new insights in understanding how altered OA bone matrix can lead to the abnormal osteocyte phenotypic changes, which is typical in OA pathogenesis. PMID:24289792

  14. Angiotensin-II-dependent Hypertension Requires Cyclooxygenase 1-derived Prostaglandin E2 and EP1 Receptor Signaling in the Subfornical Organ of the Brain

    Science.gov (United States)

    Cao, Xian; Peterson, Jeffrey R.; Wang, Gang; Anrather, Josef; Young, Colin N.; Guruju, Mallikarjuna R.; Burmeister, Melissa A.; Iadecola, Costantino; Davisson, Robin L.

    2012-01-01

    Cyclooxygenase (COX)-derived prostanoids have long been implicated in blood pressure (BP) regulation. Recently prostaglandin E2 (PGE2) and its receptor EP1R have emerged as key players in angiotensin II (Ang-II)-dependent hypertension (HTN) and related end-organ damage. However, the enzymatic source of PGE2, ie COX-1 or COX-2, and its site(s) of action are not known. The subfornical organ (SFO) is a key forebrain region that mediates systemic Ang-II-dependent HTN via reactive oxygen species (ROS). We tested the hypothesis that cross-talk between PGE2/EP1R and ROS signaling in the SFO is required for Ang-II HTN. Radiotelemetric assessment of BP revealed that HTN induced by infusion of systemic “slow-pressor” doses of Ang-II was abolished in mice with null mutations in EP1R or COX-1 but not COX-2. Slow-pressor Ang-II-evoked HTN and ROS formation in the SFO were prevented when the EP1R antagonist SC-51089 was infused directly into brains of wild-type mice, and Ang-II-induced ROS production was blunted in cells dissociated from SFO of EP1R−/− and COX-1−/− but not COX-2−/− mice. In addition, slow-pressor Ang-II infusion caused a ~3-fold increase in PGE2 levels in the SFO but not in other brain regions. Finally, genetic reconstitution of EP1R selectively in the SFO of EP1R-null mice was sufficient to rescue slow-pressor AngII-elicited HTN and ROS formation in the SFO of this model. Thus, COX-1-derived PGE2 signaling through EP1R in the SFO is required for the ROS-mediated HTN induced by systemic infusion of Ang-II, and suggests that EP1R in the SFO may provide a novel target for antihypertensive therapy. PMID:22371360

  15. IL-1β-induced, matrix metalloproteinase-3-regulated proliferation of embryonic stem cell-derived odontoblastic cells is mediated by the Wnt5 signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Ozeki, Nobuaki; Hase, Naoko; Hiyama, Taiki; Yamaguchi, Hideyuki; Kawai, Rie [Department of Endodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi 464-8651 (Japan); Kondo, Ayami [Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, Nagoya 464-8650 (Japan); Nakata, Kazuhiko [Department of Endodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi 464-8651 (Japan); Mogi, Makio, E-mail: makio@dpc.agu.ac.jp [Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, Nagoya 464-8650 (Japan)

    2014-10-15

    We previously established a method for differentiating induced pluripotent stem cells and embryonic stem (ES) cells into α2 integrin-positive odontoblast-like cells. We also reported that interleukin (IL)-1β induces matrix metalloproteinase (MMP)-3-regulated cell proliferation and suppresses apoptosis in these cells, suggesting that MMP-3 plays a potentially unique physiological role in the regeneration of odontoblast-like cells. Here, we examined whether up-regulation of MMP-3 activity by IL-1β was mediated by Wnt signaling and led to increased proliferation of odontoblast-like cells. IL-1β increased mRNA and protein levels of Wnt5a, Wnt5b and the Wnt receptor Lrp5. Exogenous Wnt5a and Wnt5b were found to increase MMP-3 mRNA, protein and activity, and interestingly the rate of proliferation in these cells. Treatment with siRNAs against Wnt5a, Wnt5b and Lrp5 suppressed the IL-1β-induced increase in MMP-3 expression and suppressed cell proliferation, an effect rescued by application of exogenous Wnt5. These results demonstrate the sequential involvement of Wnt5, Lrp5 and MMP-3 in effecting IL-1β-induced proliferation of ES cell-derived odontoblast-like cells. - Highlights: • IL-1β induces Wnt5, Lrp5/Fzd9 and MMP-3 in ES cell-derived odontoblast-like cells. • IL-1β-induced Wnt5 expression results in increased cell proliferation. • Exogenous Wnt5 increases MMP-3 activity and cell proliferation. • Exogenous Wnt5 rescues IL-1β-driven proliferation with anti-Wnt5 siRNA suppression. • IL-1β-induced cell proliferation involves Wnt5, Lrp5, and MMP-3 sequentially.

  16. ERK signaling is required for VEGF-A/VEGFR2-induced differentiation of porcine adipose-derived mesenchymal stem cells into endothelial cells.

    Science.gov (United States)

    Almalki, Sami G; Agrawal, Devendra K

    2017-05-12

    Cell-based therapy that can rejuvenate the endothelium with stimulated adipose-derived mesenchymal stem cells (AMSCs) is a promising therapeutic strategy for the re-endothelialization of denuded arteries at the stenting site. Previously, we have shown that silencing of MMP-2 and MMP-14 inhibits vascular endothelial growth factor receptor type 2 (VEGFR2) cleavage, and induces differentiation of AMSCs toward the endothelial cell (EC) lineage. In this study, we examined the underlying signaling pathways that regulate differentiation of AMSCs to ECs in vitro through VEGFR2. AMSCs were isolated from porcine abdominal adipose tissue. The isolated AMSCs were characterized by positive expression of CD29, CD44, and CD90 and negative expression of CD11b and CD45. The isolated MSCs were transfected with siRNA to silence MMP-2, MMP-14, and angiotensin receptor 2 (ATR2). Cells were suspended either in endothelial basal media (EBM) or endothelial growth media (EGM) with various treatments. Flow cytometry was performed to examine the expression of EC markers, and western blot analysis was performed to examine the expression and activity of various kinases. Scratch assay was performed to examine the cell migration. Data were analyzed by ANOVA using PRISM GraphPad. After 10 days of stimulation for EC differentiation, the morphology of AMSCs changed to a morphology similar to that of ECs. Silencing MMP-2 and MMP-14 resulted in significant decrease in the number of migrated cells compared with the EGM-only group. ATR2 siRNA transfection did not affect the migration and differentiation of AMSCs to ECs. Stimulation of AMSCs for EC differentiation with or without MMP-2 or MMP-14 siRNA resulted in significant increase in p-ERK, and significant decrease in p-JNK. There was no significant change in p-p38 in all three groups compared with the EBM group. ERK inhibition resulted in significant decrease in the expression of EC markers in the EGM, EGM + MMP-2 siRNA, and EGM + MMP-14 si

  17. Specification of embryonic stem cell-derived tissues into eye fields by Wnt signaling using rostral diencephalic tissue-inducing culture.

    Science.gov (United States)

    Sakakura, Eriko; Eiraku, Mototsugu; Takata, Nozomu

    2016-08-01

    The eyes are subdivided from the rostral diencephalon in early development. How the neuroectoderm regulates this subdivision, however, is largely unknown. Taking advantage of embryonic stem cell (ESC) culture using a Rax reporter line to monitor rostral diencephalon formation, we found that ESC-derived tissues at day 7 grown in Glasgow Minimum Expression Media (GMEM) containing knockout serum replacement (KSR) exhibited higher levels of expression of axin2, a Wnt target gene, than those grown in chemically defined medium (CDM). Surprisingly, Wnt agonist facilitated eye field-like tissue specification in CDM. In contrast, the addition of Wnt antagonist diminished eye field tissue formation in GMEM+KSR. Furthermore, the morphological formation of the eye tissue anlage, including the optic vesicle, was accompanied by Wnt signaling activation. Additionally, using CDM culture, we developed an efficient method for generating Rax+/Chx10+ retinal progenitors, which could become fully stratified retina. Here we provide a new avenue for exploring the mechanisms of eye field specification in vitro. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. MMP-2 and Notch signal pathway regulate migration of adipose-derived stem cells and chondrocytes in co-culture systems.

    Science.gov (United States)

    Zhang, Qi; Deng, Shuwen; Sun, Ke; Lin, Shiyu; Lin, Yunfeng; Zhu, Bofeng; Cai, Xiaoxiao

    2017-12-01

    The crosstalk between chondrocytes and adipose-derived stem cells (ADSCs) could regulate the secretion of multiple growth factors. However, it is not clear how the paracrine action in co-culture systems affect cell migration. This study focused on the changes of cell migration of ADSCs and chondrocytes in co-culture conditions. Primary ADSCs and chondrocytes were isolated from Sprague-Dawley rat. Transwell co-culture systems, inoculated with ADSCs and chondrocytes, were established in vitro. The morphology of the cells was observed 7 days post-seeding by inverted phase-contrast microscope. Additionally, the cytoskeleton changes were investigated by immunofluorescence staining. To detect the abundance of Vinculin, we used immunofluorescence and Western blotting. Additionally, the expression level of MMP-2, Hey1 and Hes1 was examined to determine the mechanisms of co-culture-induced cell migration changes. The migration of ADSCs and chondrocytes in co-culture conditions significantly decreased compared with that in mono-culture groups, accompanied by the decrease of filopodia and the expression level of MMP-2. The overall study showed that the migration of ADSCs and chondrocytes differs significantly depending on culture conditions. Moreover, the Notch signalling pathway may be involved in this process. Accordingly, by studying changes in migration caused by co-culture, we obtained new insight into the crosstalk between ADSCs and chondrocytes. © 2017 John Wiley & Sons Ltd.

  19. Apoptosis Signal-Regulating Kinase 1 Is Involved in Brain-Derived Neurotrophic Factor (BDNF)-Enhanced Cell Motility and Matrix Metalloproteinase 1 Expression in Human Chondrosarcoma Cells

    Science.gov (United States)

    Lin, Chih-Yang; Chang, Sunny Li-Yun; Fong, Yi-Chin; Hsu, Chin-Jung; Tang, Chih-Hsin

    2013-01-01

    Chondrosarcoma is the primary malignancy of bone that is characterized by a potent capacity to invade locally and cause distant metastasis, and is therefore associated with poor prognoses. Chondrosarcoma further shows a predilection for metastasis to the lungs. The brain-derived neurotrophic factor (BDNF) is a small molecule in the neurotrophin family of growth factors that is associated with the disease status and outcome of cancers. However, the effect of BDNF on cell motility in human chondrosarcoma cells is mostly unknown. Here, we found that human chondrosarcoma cell lines had significantly higher cell motility and BDNF expression compared to normal chondrocytes. We also found that BDNF increased cell motility and expression of matrix metalloproteinase-1 (MMP-1) in human chondrosarcoma cells. BDNF-mediated cell motility and MMP-1 up-regulation were attenuated by Trk inhibitor (K252a), ASK1 inhibitor (thioredoxin), JNK inhibitor (SP600125), and p38 inhibitor (SB203580). Furthermore, BDNF also promoted Sp1 activation. Our results indicate that BDNF enhances the migration and invasion activity of chondrosarcoma cells by increasing MMP-1 expression through a signal transduction pathway that involves the TrkB receptor, ASK1, JNK/p38, and Sp1. BDNF thus represents a promising new target for treating chondrosarcoma metastasis. PMID:23892595

  20. Systemic inflammation and liver injury following hemorrhagic shock and peripheral tissue trauma involve functional TLR9 signaling on bone marrow-derived cells and parenchymal cells.

    Science.gov (United States)

    Gill, Roop; Ruan, Xiangcai; Menzel, Christoph L; Namkoong, Seung; Loughran, Patricia; Hackam, David J; Billiar, Timothy R

    2011-02-01

    Hemorrhagic shock due to trauma (HS/T) induces an inflammatory response that can contribute to end-organ injury. The pathways involved in the initiation and propagation of HS/T-induced inflammation are incompletely understood. Here, we hypothesized that the DNA sensor TLR9 would have a role in inflammatory signaling after HS/T. Using mice expressing a nonfunctional, mutant form of TLR9, we identified a role of TLR9 in driving the initial cytokine response and liver damage in a model of hemorrhagic shock and bilateral femur fracture. Circulating DNA levels were found to correlate with the degree of tissue damage. Experiments using chimeric mice show that TLR9 on both bone marrow-derived cells and parenchymal cells are important for the TLR9-mediated liver and tissue damage, as well as systemic inflammation after HS/T. These data suggest that release of DNA may be a driver of the inflammatory response to severe injury as well as a marker of the extent of tissue damage. One of the sensors of DNA in the setting of HS/T seems to be TLR9.

  1. Attenuation of LPS-induced inflammation by ICT, a derivate of icariin, via inhibition of the CD14/TLR4 signaling pathway in human monocytes.

    Science.gov (United States)

    Wu, Jinfeng; Zhou, Junmin; Chen, Xianghong; Fortenbery, Nicole; Eksioglu, Erika A; Wei, Sheng; Dong, Jingcheng

    2012-01-01

    To evaluate the anti-inflammatory potential of ICT in LPS stimulated human innate immune cells. 3, 5, 7-Trihydroxy-4'-methoxy-8-(3-hydroxy-3- methylbutyl)-flavone (ICT) is a novel derivative of icariin, the major active ingredient of Herba Epimedii, an herb used in traditional Chinese medicine. We previously demonstrated its anti-inflammatory potential in a murine macrophage cell line as well as in mouse models. We measured TNF-α production by ELISA, TLR4/CD14 expression by flow cytometry, and NF-κB and MAPK activation by western blot all in LPS-stimulated PBMC, human monocytes, or THP-1 cells after treatment with ICT. ICT inhibited LPS-induced TNF-α production in THP-1 cells, PBMCs and human monocytes in a dose-dependent manner. ICT treatment resulted in down-regulation of the expression of CD14/TLR4 and attenuated NF-κB and MAPK activation induced by LPS. We illustrate the anti-inflammatory property of ICT in human immune cells, especially in monocytes. These effects were mediated, at least partially, via inhibition of the CD14/TLR4 signaling pathway. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Proanthocyanidins Attenuation of H2O2-Induced Oxidative Damage in Tendon-Derived Stem Cells via Upregulating Nrf-2 Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Wenshuang Sun

    2017-01-01

    Full Text Available Proanthocyanidins (PCs have shown inhibition of oxidative damage by improving Nrf-2 expression in many tissues. However, the cytoprotective effects of PCs on H2O2-induced tendon damage have not been verified. The current study was aimed at assessing the cytoprotection of PCs on the oxidative cellular toxicity of tendon-derived stem cells (TDSCs induced by H2O2. The TDSCs were isolated from patellar tendons of Sprague Dawley (SD rats, and the cells after third passage were used for subsequent experiments. The isolated cells were identified by flow cytometry assay and multidifferentiation potential assay. Cell Counting Kit-8 assay was performed to examine cell viability. Real-Time PCR and Western Blot were employed to, respectively, assess the mRNA and protein expressions of Nrf-2, GCLM, NQO-1, and HO-1. PCs significantly improved the cell viability of TDSCs. Furthermore, H2O2 upregulated Nrf-2, GCLM, NQO-1, and HO-1 without significant difference, while the proteins expressions were increased with significant difference in PCs group and PCs + H2O2 cotreated group. All the findings indicated that PCs could protect against the oxidative damage induced by H2O2 in TDSCs, and the cytoprotective effects might be due to the ability of PCs to activate the expressions of GCLM, HO-1, and NQO-1 via upregulating Nrf-2 signaling pathway.

  3. Decreased nuclear stiffness via FAK-ERK1/2 signaling is necessary for osteopontin-promoted migration of bone marrow-derived mesenchymal stem cells.

    Science.gov (United States)

    Liu, Lingling; Luo, Qing; Sun, Jinghui; Wang, Aoli; Shi, Yisong; Ju, Yang; Morita, Yasuyuki; Song, Guanbin

    2017-06-15

    Migration of bone marrow-derived mesenchymal stem cells (BMSCs) plays an important role in many physiological and pathological settings, including wound healing. During the migration of BMSCs through interstitial tissues, the movement of the nucleus must be coordinated with the cytoskeletal dynamics, which in turn affects the cell migration efficiency. Our previous study indicated that osteopontin (OPN) significantly promotes the migration of rat BMSCs. However, the nuclear behaviors and involved molecular mechanisms in OPN-mediated BMSC migration are largely unclear. In the present study, using an atomic force microscope (AFM), we found that OPN could decrease the nuclear stiffness of BMSCs and reduce the expression of lamin A/C, which is the main determinant of nuclear stiffness. Increased lamin A/C expression attenuates BMSC migration by increasing nuclear stiffness. Decreased lamin A/C expression promotes BMSC migration by decreasing nuclear stiffness. Furthermore, OPN promotes BMSC migration by diminishing lamin A/C expression and decreasing nuclear stiffness via the FAK-ERK1/2 signaling pathway. This study provides strong evidence for the role of nuclear mechanics in BMSC migration as well as new insight into the molecular mechanisms of OPN-promoted BMSC migration. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. High extracellular magnesium inhibits mineralized matrix deposition and modulates intracellular calcium signaling in human bone marrow-derived mesenchymal stem cells.

    Science.gov (United States)

    Zhang, Li; Yang, Chunxi; Li, Jiao; Zhu, Yuchang; Zhang, Xiaoling

    2014-08-08

    Mesenchymal stem cells (MSCs) have the potential to differentiate into several cell types and provide an attractive source of autologous cells for regenerative medicine. However, their cellular biology is not fully understood. Similar to Ca(2+), extracellular Mg(2+) plays an important role in the functions of the skeletal system. Here, we examined the effects of extracellular Mg(2+) on the deposition of calcium phosphate matrix and Ca(2+) signaling with or without ATP stimulation in human bone marrow-derived mesenchymal stem cells (hBMSCs). We found that high extracellular Mg(2+) concentration ([Mg(2+)]e) inhibited extracellular matrix mineralization in hBMSCs in vitro. hBMSCs also produced a dose-dependent decrease in the frequency of calcium oscillations during [Mg(2+)]e elevation with a slight suppression on oscillation amplitude. In addition, spontaneous ATP release was inhibited under high [Mg(2+)]e levels and exogenous ATP addition stimulated oscillation reappear. Taken together, our results indicate that high [Mg(2+)]e modulates calcium oscillations via suppression of spontaneous ATP release and inactivates purinergic receptors, resulting in decreased extracellular mineralized matrix deposition in hBMSCs. Therefore, the high magnesium environment created by the rapid corrosion of Mg alloys may result in the dysfunction of calcium-dependent physiology processes and be disadvantageous to hBMSCs physiology. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Ultraviolet-LIGA-based fabrication and characterization of a nonresonant drive-mode vibratory gyro/accelerometer

    Science.gov (United States)

    Verma, Payal; Zaman Khan, Khamar; Khonina, Svetlana Nikolaevna; Kazanskiy, Nikolay Lvovich; Gopal, Ram

    2016-07-01

    A dual-purpose nonresonant 2-degrees of freedom (DOF) drive-mode and 1-DOF sense-mode vibratory gyro/accelerometer fabricated using the economical ultraviolet-lithographie-galvanoformung-abformung (UV-LIGA) fabrication process using SU-8 photoresist is reported. The dual-purpose device presented is capable of detecting acceleration at the lower-frequency band and angular rate at the operating frequency band thereby functioning as both accelerometer and gyroscope. This is achieved by designing the structure such that the frequency response of the drive oscillator has two drive resonances with a flat zone between them, while the sense oscillator has one resonance, which is deliberately placed in the flat region between the two drive resonances. For angular rate detection, the device is operated in the flat zone at the sense resonance frequency at which the device is less susceptible to frequency variations due to both environmental variation and fabrication imperfections and hence is said to be operating in robust mode. The steady-state response and discrimination for angular rate and acceleration sensing have been devised using analytical modeling. The fabrication process is optimized to realize a gyro/accelerometer that has a 9-μm-thick nickel structural layer and 4-μm capacitive gaps. The overall miniature device size is 2.0 mm×1.9 mm. The experimental frequency response of the fabricated devices shows drive-mode resonances at 2.85 and 4.96 kHz and sense resonance at 3.85 kHz compared to the respective design values of drive-mode resonance frequencies 2.97 and 4.81 kHz and sense resonance frequency of 4 kHz. To demonstrate the dual-purpose capability of the device, acceleration characterization has been carried out and presented. The fabricated sensor is packaged in a ceramic package and interfaced with a MS3110 differential capacitive read out IC to characterize the acceleration response of the sensor, using an out-of-plane shaker. The bandwidth for

  6. Influence of the Radial Clearance of a Squeeze Film Damper on the Vibratory Behavior of a Single Spool Gas Turbine Designed for Unmanned Aerial Vehicle Applications

    Directory of Open Access Journals (Sweden)

    Geraldo Creci

    2017-01-01

    Full Text Available This study presents a numerical investigation using the finite element method on the vibratory behavior of a single spool gas turbine designed for unmanned aerial vehicle applications. The shaft of the rotor-bearing system is supported on a front bearing composed of a deep groove ball bearing with a vibration absorber element and a rear squeeze film damper bearing. Three radial clearances for the squeeze film damper were analyzed to determine the best geometric configuration for the rear bearing, considering the rotordynamic performance of the entire system. Whirl speeds and unbalanced system responses were carefully evaluated to determine the best radial clearance for the squeeze film damper. After defining the best radial clearance, a transient analysis was performed to simulate the transition of the system through resonance, and a spectral map is presented to illustrate the vibratory behavior of the system considering the influence of all related important frequencies. The rotordynamic behavior of the system is predicted, and vibration problems are avoided. Its mechanical drawings were released to manufacturing, and the first prototype is in the experimental test phase, thus indicating that the numerical results presented in this study are consistent.

  7. Brain-derived neurotrophic factor (BDNF) -TrKB signaling modulates cancer-endothelial cells interaction and affects the outcomes of triple negative breast cancer.

    Science.gov (United States)

    Tsai, Yi-Fang; Tseng, Ling-Ming; Hsu, Chih-Yi; Yang, Muh-Hwa; Chiu, Jen-Hwey; Shyr, Yi-Ming

    2017-01-01

    There is good evidence that the tumor microenvironment plays an important role in cancer metastasis and progression. Our previous studies have shown that brain-derived neurotrophic factor (BDNF) participates in the process of metastasis and in the migration of cancer cells. The aim of this study was to investigate the role of BDNF on the tumor cell microenvironment, namely, the cancer cell-endothelial cell interaction of TNBC cells. We conducted oligoneucleotide microarray analysis of potential biomarkers that are able to differentiate recurrent TNBC from non-recurrent TNBC. The MDA-MB-231 and human endothelial HUVEC lines were used for this study and our approaches included functional studies, such as migration assay, as well as Western blot and real-time PCR analysis of migration and angiogenic signaling. In addition, we analyzed the survival outcome of TNBC breast cancer patients according to their expression level of BDNF using clinical samples. The results demonstrated that BDNF was able to bring about autocrinal (MDA-MB-231) and paracrinal (HUVECs) regulation of BDNF-TrkB gene expression and this affected cell migratory activity. The BDNF-induced migratory activity was blocked by inhibitors of ERK, PI3K and TrkB when MDA-MB-231 cells were examined, but only an inhibitor of ERK blocked this activity when HUVEC cells were used. Furthermore, decreased migratory activity was found for △BDNF and △TrkB cell lines. Ingenuity pathway analysis (IPA) of MDA-MB-231 cells showed that BDNF is a key factor that is able to regulate a network made up of metalloproteases and calmodulin. Protein expression levels in a tissue array of tumor slices were found to be correlated with patient prognosis and the results showed that there was significant correlation of TrkB expression, but not of BDNF. expressionwith patient DFS and OS. Our study demonstrates that up-regulation of the BDNF signaling pathway seems tobe involved in the mechanism associated with early recurrence in

  8. Brain-derived neurotrophic factor/tropomyosin-related kinase B signaling pathway contributes to the aggressive behavior of lung squamous cell carcinoma.

    Science.gov (United States)

    Ozono, Keigo; Ohishi, Yoshihiro; Onishi, Hideya; Nakamura, Katsuya; Motoshita, Junichi; Kato, Masato; Nakanishi, Ryoichi; Nakamura, Masafumi; Oda, Yoshinao

    2017-11-01

    The tropomyosin-related kinase (Trk) family consists of TrkA, TrkB, and TrkC, which play essential roles in tumor progression and/or suppression in various cancers. Little is known about the biological significance of the Trk family in human lung squamous cell carcinoma (SCC). Here we investigated the clinical significance of the protein expression of Trk family members in samples from 99 SCC patients, and we explored the relationship between invasion/proliferation activities and Trk expression using lung SCC cell lines to clarify the biological significance of the Trk family in lung SCC. Immunohistochemical high expression of TrkB was significantly correlated with vascular invasion (P=0.004), lymph node metastasis (P<0.001), and advanced stage (P=0.0015). The overall survival of the patients with TrkB-high expression was significantly shorter than those with TrkB-low expression (P=0.0110). TrkA/TrkC expressions were not predictors of poor prognosis. An in vitro assay demonstrated that the inhibition of brain-derived neurotrophic factor (BDNF) (a TrkB ligand) and TrkB by K252a (a Trk inhibitor) or siRNA (BDNF-siRNA, TrkB-siRNA) suppressed the invasion, migration, and proliferative activities of lung SCC cells. The administration of recombinant human BDNF (rhBDNF) enhanced the invasion, migration, and proliferation activities, which were abrogated by K252a. TrkB-siRNA transfection increased the protein expression of E-cadherin and decreased vimentin expressions in lung SCC cells. Matrix metalloproteinase-2 (MMP-2)-mediated gelatin degradations were decreased in lung SCC cells transfected with TrkB-siRNA. Thus, TrkB-high expression is an indicator of poor prognosis in lung SCC, probably due to invasion/proliferation activities promoted by the BDNF/TrkB signaling pathway, which could become a therapeutic target for lung SCC.

  9. Simulating the effects of scintillation on transionospheric signals with a two-way phase screen constructed from ALTAIR phase-derived TEC

    Science.gov (United States)

    Caton, R. G.; Carrano, C. S.; Alcala, C. M.; Groves, K. M.; Beach, T.; Sponseller, D.

    2009-02-01

    Severe scintillation on transionospheric radio signals caused by small-scale plasma irregularities can greatly disrupt wideband communication, surveillance, and navigation systems. Development of techniques to mitigate the effects of scintillation requires accurate characterization of the ionospheric propagation channel. To achieve this goal, multiple campaigns were conducted as part of the joint U.S. -UK Wideband Ionospheric Distortion Experiment to obtain ionospheric signatures from various instruments located on Kwajalein Atoll. We use tracking data from the VHF/UHF Advanced Research Project Agency Long-Range Tracking and Instrumentation Radar for overflights of passive calibration spheres in low-Earth orbit to demonstrate the validity of a one-dimensional (1-D) phase screen model to represent the propagation channel through a disturbed ionosphere. The 1-D phase screen is constructed from radar phase-derived estimates of the total electron content. We present a detailed comparison of simulated radar cross section after propagation through the phase screen with observed radar returns under both disturbed and quiet ionospheric conditions. Successful reproduction of radar amplitude enhancements and fades adds to our understanding of small-scale plasma irregularities and moves us toward our goal of providing precise predictions of radar system performance. Doing so will allow for the development of better mitigation/compensation algorithms for detrimental ionospheric effects. Result from this study also provide an assessment of the tools required for incorporating in situ density measurements along with phase screen theory into situational awareness products to offer an accurate nowcast/forecast of system impacts to users in the communication, navigation, and surveillance communities.

  10. Ultrasound Enhances the Expression of Brain-Derived Neurotrophic Factor in Astrocyte Through Activation of TrkB-Akt and Calcium-CaMK Signaling Pathways.

    Science.gov (United States)

    Liu, Shing-Hwa; Lai, Yi-Long; Chen, Bo-Lin; Yang, Feng-Yi

    2017-06-01

    Low-intensity pulsed ultrasound (LIPUS) stimulation has been shown to increase the expression of brain-derived neurotrophic factor (BDNF) in astrocytes of an in vitro model and rat brains of an in vivo model; however, their molecular mechanisms are still not well clarified. Here, we investigated the underlying mechanisms of BDNF enhancement by LIPUS in rat cerebral cortex astrocytes. After LIPUS stimulation in astrocytes, the protein and mRNA expressions were measured by western blot and RT-PCR, respectively. The concentration of intracellular calcium was determined spectrophotometrically. The results showed that LIPUS enhanced the phosphorylation of tropomyosin-related kinase B (TrkB) and Akt but had no effect on Erk1/2 phosphorylation. Additionally, LIPUS increased the intracellular concentration of calcium and enhanced the protein levels of calmodulin-dependent kinase (CaMK) II and CaMKIV. LIPUS also activated the phosphorylation of NF-κB-p65 but did not promote the activation of cAMP response element-binding protein (CREB). Taken together, our results suggest that LIPUS stimulation upregulates BDNF production in astrocytes through the activation of NF-κB via the TrkB/PI3K/Akt and calcium/CaMK signaling pathways. BDNF has emerged as a major molecular player in the regulation of neural circuit development and function. Therefore, LIPUS stimulation may play a crucial and beneficial role in neurodegenerative diseases. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. Pinocembrin, a major flavonoid in propolis, improves the biological functions of EPCs derived from rat bone marrow through the PI3K-eNOS-NO signaling pathway.

    Science.gov (United States)

    Yang, Nana; Qin, Shucun; Wang, Mengzan; Chen, Bin; Yuan, Na; Fang, Yongqi; Yao, Shutong; Jiao, Peng; Yu, Yang; Zhang, Ying; Wang, Jiafu

    2013-08-01

    The number and quality of endothelial progenitor cells (EPCs) are damaged to varying degrees in patients at risk for developing atherosclerosis. The improvement of the quantity and functions of EPCs can enhance repair of injured endothelial monolayer resulting in inhibiting atherosclerosis. The purpose of this study was to investigate the effect of pinocembrin (PIN), a major flavonoid in propolis on the differentiation and biological functions of EPCs and the potential mechanisms of these effects. Flow cytometry analysis revealed that PIN treatment increased the number of CD34(+), CD133(+), FLK-1(+), CD133(+)/FLK-1(+) and CD34(+)/FLK-1(+) mononuclear cells (MNCs) in the peripheral blood of apoE(-/-) mice compared to untreated control mice. In vitro PIN treatment significantly increased the number of CD34(+), CD133(+), FLK-1(+) and CD133(+)/FLK-1(+) MNCs derived from SD bone marrow compared to untreated controls by 42.1, 84.6, 165.9 and 23.1 %, respectively. Additionally, PIN can improve biological functions of EPCs, such as proliferation, migration, adhesion, and in vitro tube formation and NO release. All of these improvements were inhibited by LY294002, while L-NAME only inhibited the PIN-induced increase in EPC proliferation and adhesion. We conclude that PIN can both promote the differentiation of EPCs in vitro and ex vivo and improve the biological functions of EPCs. The PI3K-eNOS-NO signaling pathway may be involved in the PIN-induced increase in the proliferation and adhesion of EPCs.

  12. Stromal cell-derived factor-1 (SDF-1) enhances cells invasion by αvβ6 integrin-mediated signaling in ovarian cancer.

    Science.gov (United States)

    Xue, Baoyao; Wu, Weiguang; Huang, Kan; Xie, Tingting; Xu, Xiaobo; Zhang, Hongju; Qi, Chunlei; Ge, Junli; Yu, Yuecheng

    2013-08-01

    Ovarian carcinoma is a common gynecological malignancy and a great threat to health as a result of metastasis. The chemokine stromal-derived factor (SDF-1) plays multiple roles in tumor pathogenesis. However, the precise molecular mechanism underlying SDF-1-induced ovarian cancer cell invasion is still undefined. αvβ6 integrin is an important factor in tumor progression. Therefore, we speculate that SDF-1-enhanced ovarian cancer cell invasion is related to αvβ6 integrin-mediated signaling. After culturing with SDF-1, an obvious time- and dose-dependent increase in αvβ6 integrin was demonstrated. Furthermore, CXC receptor 4 (CXCR4) was responsible for SDF-1-induced αvβ6 integrin expression. Simultaneously, SDF-1 was found to dramatically enhance extracellular matrix degradation via urokinase-type plasminogen activator (uPA) expression and cell invasion by αvβ6 integrin expression; these reinforce failed to be increased when pretreatment was performed with the CXCR4 inhibitor AMD3100 or anti-αvβ6 integrin antibody, respectively. In addition, αvβ6 integrin induced the phosphorylation of p38 MAPK and PI3 K/Akt, contributing to the up-regulation of uPA, as treatment with the specific inhibitor for p38 mitogen-activated protein kinases (MAPK) (SB203580) or phosphatidylinositol 3-kinase (PI3 K)/Akt (LY294002) strikingly abrogated uPA expression. Taken together, these results demonstrated that SDF-1 enhanced ovarian cancer cell invasion through αvβ6 integrin-mediated uPA expression via the p38 MAPK and PI3 K/Akt pathway. Consequently, our findings will provide a new explanation about how SDF-1 aggravates the pathogenesis of ovarian cancer.

  13. CD20-selective inhibition of CD47-SIRPα “don't eat me” signaling with a bispecific antibody-derivative enhances the anticancer activity of daratumumab, alemtuzumab and obinutuzumab

    OpenAIRE

    van Bommel, Peter E.; He, Yuan; Schepel, Ilona; Hendriks, Mark A. J. M.; Wiersma, Valerie R.; van Ginkel, Robert J.; van Meerten, Tom; Ammatuna, Emanuele; Huls, Gerwin; Samplonius, Douwe F.; Helfrich, Wijnand; Bremer, Edwin

    2017-01-01

    ABSTRACT Here, we report on a novel bispecific antibody-derivative, designated RTX-CD47, with unique capacity for CD20-directed inhibition of CD47-SIRPα “don't eat me” signaling. RTX-CD47 comprises a CD20-targeting scFv antibody fragment derived from rituximab fused in tandem to a CD47-blocking scFv. Single agent treatment with RTX-CD47 triggered significant phagocytic removal of CD20pos/CD47pos malignant B-cells, but not of CD20neg/CD47pos cells, and required no pro-phagocytic FcR-mediated s...

  14. Quinazoline derivative compound (11d as a novel angiogenesis inhibitor inhibiting VEGFR2 and blocking VEGFR2-mediated Akt/mTOR /p70s6k signaling pathway

    Directory of Open Access Journals (Sweden)

    Zeng Li

    2016-04-01

    Conclusion:The mechanism underlying the anti-angiogenic activity of the quinazoline derivative 11d possibly involves the inhibition of VEGFR2 and the downregulation of VEGF, VEGFR2, and the VEGFR2-mediated Akt/mTOR/p70s6k signaling pathway. Overall, the findings indicate that the studied class of compounds is a source of potential antiproliferative and anti-angiogenic agents, which must be further investigated.

  15. Wnt/β‐catenin‐signaling and the formation of Müller glia‐derived progenitors in the chick retina

    National Research Council Canada - National Science Library

    Gallina, Donika; Palazzo, Isabella; Steffenson, Lillia; Todd, Levi; Fischer, Andy J

    2016-01-01

    ...‐signaling influences the formation of MGPCs in the chick retina in vivo . In NMDA‐damaged retinas where MGPCs are known to form, we find dynamic changes in retinal levels of potential readouts of Wnt...

  16. MicroRNA-100 shuttled by mesenchymal stem cell-derived exosomes suppresses in vitro angiogenesis through modulating the mTOR/HIF-1α/VEGF signaling axis in breast cancer cells.

    Science.gov (United States)

    Pakravan, Katayoon; Babashah, Sadegh; Sadeghizadeh, Majid; Mowla, Seyed Javad; Mossahebi-Mohammadi, Majid; Ataei, Farangis; Dana, Nasim; Javan, Mohammad

    2017-10-01

    Human mesenchymal stem cells (MSCs) have been shown to be involved in the formation and modulation of tumor stroma and in interacting with tumor cells, partly through their secretome. Exosomes are nano-sized intraluminal multi-vesicular bodies secreted by most types of cells and have been found to mediate intercellular communication through the transfer of genetic information via coding and non-coding RNAs to recipient cells. Since exosomes are considered as protective and enriched sources of shuttle microRNAs (miRNAs), we hypothesized that exosomal transfer of miRNAs from MSCs may affect tumor cell behavior, particularly angiogenesis. Exosomes derived from MSCs were isolated and characterized by scanning electron microscopy analyses, dynamic light scattering measurements, and Western blotting. Fold changes in miR-100 expression levels were calculated in exosomes and their corresponding donor cells by qRT-PCR. The effects of exosomal transfer of miR-100 from MSCs were assessed by qRT-PCR and Western blotting of the mTOR/HIF-1α/VEGF signaling axis in breast cancer cells. The quantification of secreted VEGF protein was determined by enzyme-linked immunosorbent assay. The putative paracrine effects of MSC-derived exosomes on tumor angiogenesis were explored by in vitro angiogenesis assays including endothelial cell proliferation, migration and tube formation assays. We found that MSC-derived exosomes induce a significant and dose-dependent decrease in the expression and secretion of vascular endothelial growth factor (VEGF) through modulating the mTOR/HIF-1α signaling axis in breast cancer-derived cells. We also found that miR-100 is enriched in MSC-derived exosomes and that its transfer to breast cancer-derived cells is associated with the down-regulation of VEGF in a time-dependent manner. The putative role of exosomal miR-100 transfer in regulating VEGF expression was substantiated by the ability of anti-miR-100 to rescue the inhibitory effects of MSC-derived

  17. Hybrid Cells Derived from Human Breast Cancer Cells and Human Breast Epithelial Cells Exhibit Differential TLR4 and TLR9 Signaling

    Directory of Open Access Journals (Sweden)

    Songül Tosun

    2016-05-01

    Full Text Available TLRs are important receptors of cells of the innate immune system since they recognize various structurally conserved molecular patterns of different pathogens as well as endogenous ligands. In cancer, the role of TLRs is still controversial due to findings that both regression and progression of tumors could depend on TLR signaling. In the present study, M13SV1-EGFP-Neo human breast epithelial cells, MDA-MB-435-Hyg human breast cancer cells and two hybrids M13MDA435-1 and -3 were investigated for TLR4 and TLR9 expression and signaling. RT-PCR data revealed that LPS and CpG-ODN induced the expression of pro-inflammatory cytokines, like IFN-β, TNF-α, IL-1β and IL-6 in hybrid cells, but not parental cells. Interestingly, validation of RT-PCR data by Western blot showed detectable protein levels solely after LPS stimulation, suggesting that regulatory mechanisms are also controlled by TLR signaling. Analysis of pAKT and pERK1/2 levels upon LPS and CpG-ODN stimulation revealed a differential phosphorylation pattern in all cells. Finally, the migratory behavior of the cells was investigated showing that both LPS and CpG-ODN potently blocked the locomotory activity of the hybrid cells in a dose-dependent manner. In summary, hybrid cells exhibit differential TLR4 and TLR9 signaling.

  18. The regulation of Hh/Gli1 signaling cascade involves Gsk3β- mediated mechanism in estrogen-derived endometrial hyperplasia.

    Science.gov (United States)

    Kaushal, Jyoti Bala; Sankhwar, Pushplata; Kumari, Suparna; Popli, Pooja; Shukla, Vinay; Hussain, Mohd Kamil; Hajela, Kanchan; Dwivedi, Anila

    2017-07-26

    The present study was undertaken to explore the functional involvement of Hh signaling and its regulatory mechanism in endometrial hyperplasia. Differential expression of Hh signaling molecules i.e., Ihh, Shh, Gli1 or Gsk3β was observed in endometrial hyperplasial (EH) cells as compared to normal endometrial cells. Estradiol induced the expression of Hh signaling molecules and attenuated the expression of Gsk3β whereas anti-estrogen (K1) or progestin (MPA) suppressed these effects in EH cells. Cyclopamine treatment or Gli1 siRNA knockdown suppressed the growth of EH cells and reduced the expression of proliferative markers. Estradiol also induced the nuclear translocation of Gli1 which was suppressed by both MPA and K1 in EH cells. While exploring non-canonical mechanism, LY-294002 (Gsk3β activator) caused a decrease in Gli1 expression indicating the involvement of Gsk3β in Gli1 regulation. Further, Gsk3β silencing promoted the expression and nuclear translocation of Gli1 demonstrating that Gsk3β serves as a negative kinase regulator of Gli1 in EH cells. Similar attenuation of Hh signaling molecules was observed in rats with uterine hyperplasia undergoing anti-estrogen treatment. The study suggested that Hh/Gli1 cascade (canonical pathway) as well as Gsk3β-Gli1 crosstalk (non-canonical pathway) play crucial role in estrogen-dependent cell proliferation in endometrial hyperplasia.

  19. Analysis of receptor signaling pathways by mass spectrometry: identification of vav-2 as a substrate of the epidermal and platelet-derived growth factor receptors

    DEFF Research Database (Denmark)

    Pandey, A; Podtelejnikov, A V; Blagoev, B

    2000-01-01

    Oligomerization of receptor protein tyrosine kinases such as the epidermal growth factor receptor (EGFR) by their cognate ligands leads to activation of the receptor. Transphosphorylation of the receptor subunits is followed by the recruitment of signaling molecules containing src homology 2 (SH2...

  20. CD20-selective inhibition of CD47-SIRPα “don't eat me” signaling with a bispecific antibody-derivative enhances the anticancer activity of daratumumab, alemtuzumab and obinutuzumab

    Science.gov (United States)

    van Bommel, Peter E.; He, Yuan; Schepel, Ilona; Hendriks, Mark A. J. M.; Wiersma, Valerie R.; van Ginkel, Robert J.; van Meerten, Tom; Ammatuna, Emanuele; Huls, Gerwin; Samplonius, Douwe F.; Helfrich, Wijnand; Bremer, Edwin

    2018-01-01

    ABSTRACT Here, we report on a novel bispecific antibody-derivative, designated RTX-CD47, with unique capacity for CD20-directed inhibition of CD47-SIRPα “don't eat me” signaling. RTX-CD47 comprises a CD20-targeting scFv antibody fragment derived from rituximab fused in tandem to a CD47-blocking scFv. Single agent treatment with RTX-CD47 triggered significant phagocytic removal of CD20pos/CD47pos malignant B-cells, but not of CD20neg/CD47pos cells, and required no pro-phagocytic FcR-mediated signaling. Importantly, treatment with RTX-CD47 synergistically enhanced the phagocytic elimination of primary malignant B cells by autologous phagocytic effector cells as induced by therapeutic anticancer antibodies daratumumab (anti-CD38), alemtuzumab (anti-CD52) and obinutuzumab (anti-CD20). In conclusion, RTX-CD47 blocks CD47 “don't eat me” signaling by cancer cells in a CD20-directed manner with essentially no activity towards CD20neg/CD47pos cells and enhances the activity of therapeutic anticancer antibodies directed to B-cell malignancies. PMID:29308308

  1. Small Molecule DFPM Derivative-Activated Plant Resistance Protein Signaling in Roots Is Unaffected by EDS1 Subcellular Targeting Signal and Chemical Genetic Isolation of victr R-Protein Mutants.

    Science.gov (United States)

    Kunz, Hans-Henning; Park, Jiyoung; Mevers, Emily; García, Ana V; Highhouse, Samantha; Gerwick, William H; Parker, Jane E; Schroeder, Julian I

    2016-01-01

    The small molecule DFPM ([5-(3,4-dichlorophenyl)furan-2-yl]-piperidine-1-ylmethanethione) was recently shown to trigger signal transduction via early effector-triggered immunity signaling genes including EDS1 and PAD4 in Arabidopsis thaliana accession Col-0. Chemical genetic analyses of A. thaliana natural variants identified the plant Resistance protein-like Toll/Interleukin1 Receptor (TIR)-Nucleotide Binding (NB)-Leucine-Rich Repeat (LRR) protein VICTR as required for DFPM-mediated root growth arrest. Here a chemical genetic screen for mutants which disrupt DFPM-mediated root growth arrest in the Col-0 accession identified new mutant alleles of the TIR-NB-LRR gene VICTR. One allele, victr-6, carries a Gly216-to-Asp mutation in the Walker A domain supporting an important function of the VICTR nucleotide binding domain in DFPM responses consistent with VICTR acting as a canonical Resistance protein. The essential nucleo-cytoplasmic regulator of TIR-NB-LRR-mediated effector-triggered immunity, EDS1, was reported to have both nuclear and cytoplasmic actions in pathogen resistance. DFPM was used to investigate the requirements for subcellular EDS1 localization in DFPM-mediated root growth arrest. EDS1-YFP fusions engineered to localize mainly in the cytoplasm or the nucleus by tagging with a nuclear export signal (NES) or a nuclear localization signal (NLS), respectively, were tested. We found that wild-type EDS1-YFP and both the NES and NLS-tagged EDS1 variants were induced by DFPM treatments and fully complemented eds1 mutant plants in root responses to DFPM, suggesting that enrichment of EDS1 in either compartment could confer DFPM-mediated root growth arrest. We further found that a light and O2-dependent modification of DFPM is necessary to mediate DFPM signaling in roots. Chemical analyses including Liquid Chromatography-Mass Spectrometry and High-Resolution Atmospheric Pressure Chemical Ionization Mass Spectrometry identified a DFPM modification product that is

  2. NADPH oxidase 2-derived reactive oxygen species signal contributes to bradykinin-induced matrix metalloproteinase-9 expression and cell migration in brain astrocytes.

    Science.gov (United States)

    Lin, Chih-Chung; Hsieh, Hsi-Lung; Shih, Ruey-Horng; Chi, Pei-Ling; Cheng, Shin-Ei; Chen, Jin-Chung; Yang, Chuen-Mao

    2012-11-23

    Matrix metalloproteinase-9 (MMP-9) plays a crucial role in pathological processes of brain inflammation, injury, and neurodegeneration. Moreover, bradykinin (BK) induces the expression of several inflammatory proteins in brain astrocytes. Recent studies have suggested that increased oxidative stress is implicated in the brain inflammation and injury. However, whether BK induced MMP-9 expression mediated through oxidative stress remains virtually unknown. Herein we investigated the role of redox signals in BK-induced MMP-9 expression in rat brain astrocytes (RBA-1 cells). In the study, we first demonstrated that reactive oxygen species (ROS) plays a crucial role in BK-induced MMP-9 expression in cultured brain astrocytes (in vitro) and animal brain tissue (in vivo) models. Next, BK-induced MMP-9 expression is mediated through a Ca2+-mediated PKC-α linking to p47phox/NADPH oxidase 2 (Nox2)/ROS signaling pathway. Nox2-dependent ROS generation led to activation and up-regulation of the downstream transcriptional factor AP-1 (i.e. c-Fos and c-Jun), which bound to MMP-9 promoter region, and thereby turned on transcription of MMP-9 gene. Functionally, BK-induced MMP-9 expression enhanced astrocytic migration. These results demonstrated that in RBA-1 cells, activation of AP-1 (c-Fos/c-Jun) by the PKC-α-mediated Nox2/ROS signals is essential for up-regulation of MMP-9 and cell migration enhanced by BK.

  3. NADPH oxidase 2-derived reactive oxygen species signal contributes to bradykinin-induced matrix metalloproteinase-9 expression and cell migration in brain astrocytes

    Directory of Open Access Journals (Sweden)

    Lin Chih-Chung

    2012-11-01

    Full Text Available Abstract Background Matrix metalloproteinase-9 (MMP-9 plays a crucial role in pathological processes of brain inflammation, injury, and neurodegeneration. Moreover, bradykinin (BK induces the expression of several inflammatory proteins in brain astrocytes. Recent studies have suggested that increased oxidative stress is implicated in the brain inflammation and injury. However, whether BK induced MMP-9 expression mediated through oxidative stress remains virtually unknown. Herein we investigated the role of redox signals in BK-induced MMP-9 expression in rat brain astrocytes (RBA-1 cells. Results In the study, we first demonstrated that reactive oxygen species (ROS plays a crucial role in BK-induced MMP-9 expression in cultured brain astrocytes (in vitro and animal brain tissue (in vivo models. Next, BK-induced MMP-9 expression is mediated through a Ca2+-mediated PKC-α linking to p47phox/NADPH oxidase 2 (Nox2/ROS signaling pathway. Nox2-dependent ROS generation led to activation and up-regulation of the downstream transcriptional factor AP-1 (i.e. c-Fos and c-Jun, which bound to MMP-9 promoter region, and thereby turned on transcription of MMP-9 gene. Functionally, BK-induced MMP-9 expression enhanced astrocytic migration. Conclusions These results demonstrated that in RBA-1 cells, activation of AP-1 (c-Fos/c-Jun by the PKC-α-mediated Nox2/ROS signals is essential for up-regulation of MMP-9 and cell migration enhanced by BK.

  4. Multi-technique approach for deriving a VLBI signal extra-path variation model induced by gravity: the example of Medicina

    Science.gov (United States)

    Sarti, P.; Abbondanza, C.; Negusini, M.; Vittuari, L.

    2009-09-01

    During the measurement sessions gravity might induce significant deformations in large VLBI telescopes. If neglected or mismodelled, these deformations might bias the phase of the incoming signal thus corrupting the estimate of some crucial geodetic parameters (e.g. the height component of VLBI Reference Point). This paper describes a multi-technique approach implemented for measuring and quantifying the gravity-dependent deformations experienced by the 32-m diameter VLBI antenna of Medicina (Northern Italy). Such an approach integrates three different methods: Terrestrial Triangulations and Trilaterations (TTT), Laser Scanning (LS) and a Finite Element Model (FEM) of the antenna. The combination of the observations performed with these methods allows to accurately define an elevation-dependent model of the signal path variation which appears to be, for the Medicina telescope, non negligible. In the range [0,90] deg the signal path increases monotonically by almost 2 cm. The effect of such a variation has not been introduced in actual VLBI analysis yet; nevertheless this is the task we are going to pursue in the very next future.

  5. Camptothecin inhibits platelet-derived growth factor-BB-induced proliferation of rat aortic vascular smooth muscle cells through inhibition of PI3K/Akt signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Park, Eun-Seok [Department of Applied Biochemistry, Division of Life Science, College of Health and Biomedical Science, Konkuk University, Chungju, Chungbuk (Korea, Republic of); Kang, Shin-il [College of Pharmacy Medical Research Center, Chungbuk National University, Cheongju (Korea, Republic of); Yoo, Kyu-dong [Hazardous Substances Analysis Division, Gwangju Regional Food and Drug Administration, Gwangju (Korea, Republic of); Lee, Mi-Yea [Department of Nursing Kyungbok University, Pocheon (Korea, Republic of); Yoo, Hwan-Soo; Hong, Jin-Tae [College of Pharmacy Medical Research Center, Chungbuk National University, Cheongju (Korea, Republic of); Shin, Hwa-Sup [Department of Applied Biochemistry, Division of Life Science, College of Health and Biomedical Science, Konkuk University, Chungju, Chungbuk (Korea, Republic of); Kim, Bokyung [Department of Physiology, Konkuk Medical School, Konkuk University, Chungju, Chungbuk (Korea, Republic of); Yun, Yeo-Pyo, E-mail: ypyun@chungbuk.ac.kr [College of Pharmacy Medical Research Center, Chungbuk National University, Cheongju (Korea, Republic of)

    2013-04-15

    The abnormal proliferation of vascular smooth muscle cells (VSMCs) in arterial wall is a major cause of vascular disorders such as atherosclerosis and restenosis after angioplasty. In this study, we investigated not only the inhibitory effects of camptothecin (CPT) on PDGF-BB-induced VSMC proliferation, but also its molecular mechanism of this inhibition. CPT significantly inhibited proliferation with IC50 value of 0.58 μM and the DNA synthesis of PDGF-BB-stimulated VSMCs in a dose-dependent manner (0.5–2 μM ) without any cytotoxicity. CPT induced the cell cycle arrest at G0/G1 phase. Also, CPT decreased the expressions of G0/G1-specific regulatory proteins including cyclin-dependent kinase (CDK)2, cyclin D1 and PCNA in PDGF-BB-stimulated VSMCs. Pre-incubation of VSMCs with CPT significantly inhibited PDGF-BB-induced Akt activation, whereas CPT did not affect PDGF-receptor beta phosphorylation, extracellular signal-regulated kinase (ERK) 1/2 phosphorylation and phospholipase C (PLC)-γ1 phosphorylation in PDGF-BB signaling pathway. Our data showed that CPT pre-treatment inhibited VSMC proliferation, and that the inhibitory effect of CPT was enhanced by LY294002, a PI3K inhibitor, on PDGF-BB-induced VSMC proliferation. In addition, inhibiting the PI3K/Akt pathway by LY294002 significantly enhanced the suppression of PCNA expression and Akt activation by CPT. These results suggest that the anti-proliferative activity of CPT is mediated in part by downregulating the PI3K/Akt signaling pathway. - Highlights: ► CPT inhibits proliferation of PDGF-BB-induced VSMC without cytotoxicity. ► CPT arrests the cell cycle in G0/G1 phase by downregulation of cyclin D1 and CDK2. ► CPT significantly attenuates Akt phosphorylation in PDGF-BB signaling pathway. ► LY294002 enhanced the inhibitory effect of CPT on VSMC proliferation. ► Thus, CPT is mediated by downregulating the PI3K/Akt signaling pathway.

  6. Human Gingiva-Derived Mesenchymal Stem Cells Inhibit Xeno-Graft-versus-Host Disease via CD39?CD73?Adenosine and IDO Signals

    OpenAIRE

    Huang, Feng; Chen, Maogen; Chen, Weiqian; Gu, Jian; Yuan, Jia; Xue, Yaoqiu; Dang, Junlong; Su, Wenru; Wang, Julie; Zadeh, Homayoun H.; He, Xiaoshun; Rong, Limin; Olsen, Nancy; Zheng, Song Guo

    2017-01-01

    Mesenchymal stem cells have the capacity to maintain immune homeostasis and prevent autoimmunity. We recently reported that human-derived gingival mesenchymal stem cells (GMSCs) have strong capacity to suppress immune responses and T cell-mediated collagen-induced arthritis in animals. However, it is unclear whether these cells can suppress human T cell-mediated diseases. Here, we used a xenogenic GVHD model in the NOD/SCID mouse, which is a useful preclinical construct for evaluating the the...

  7. IL-1β Induces MMP-9-Dependent Brain Astrocytic Migration via Transactivation of PDGF Receptor/NADPH Oxidase 2-Derived Reactive Oxygen Species Signals.

    Science.gov (United States)

    Yang, Chuen-Mao; Hsieh, Hsi-Lung; Yu, Ping-Hsien; Lin, Chih-Chung; Liu, Shiau-Wen

    2015-08-01

    Matrix metalloproteinase-9 (MMP-9) plays a crucial role in pathological processes of brain inflammation, injury, and neurodegeneration. Moreover, cytokines such as interleukin-1β (IL-1β) induce expression of several inflammatory mediators in brain astrocytes, which may be important for brain inflammatory disorders. Recent studies have implicated that increased oxidative stress may contribute to the brain injury and inflammation. However, whether IL-1β-induced MMP-9 expression mediated through oxidative stress remains unclear. Therefore, we investigated the role of redox signals in IL-1β-induced MMP-9 expression in rat brain astrocytes (RBA-1 cells). Herein, we first demonstrated that reactive oxygen species (ROS) play a crucial role in ILβ-induced MMP-9 expression by zymography, real-time PCR, and ROS staining in cultured RBA-1 cells. Next, IL-1β-induced MMP-9 expression is mediated through a c-Src-mediated transactivation of PDGFR/PI3K/Akt cascade linking to p47(phox)/NADPH oxidase 2 (Nox2)/ROS signaling pathway. Nox2-dependent ROS generation led to activation of MAPKs and the downstream transcription factors NF-κB and AP-1 (i.e., ATF2), which enhanced MMP-9 promoter activity, and thereby turned on transcription of MMP-9 gene. Functionally, IL-1β-induced MMP-9 expression promoted astrocytic migration. These results demonstrated that in RBA-1 cells, activation of NF-κB and AP-1 (ATF2) by the c-Src/PDGFR/PI3K/Akt-mediated Nox2/ROS/MAPKs signals is required for upregulation of MMP-9 and cell migration enhanced by IL-1β.

  8. EFFECT OF MECHANICAL VIBRATION GENERATED IN OSCILLATING/VIBRATORY PLATFORM ON THE CONCENTRATION OF PLASMA BIOMARKERS AND ON THE WEIGHT IN RATS

    Science.gov (United States)

    Frederico, Éric Heleno Freire Ferreira; de Sá-Caputo, Danúbia da Cunha; Moreira-Marconi, Eloá; Guimarães, Carlos Alberto Sampaio; Cardoso, André Luiz Bandeira Dionísio; Dionello, Carla da Fontoura; Morel, Danielle Soares; Sousa-Gonçalves, Cintia Renata; Paineiras-Domingos, Laisa Liana; Cavalcanti, Rebeca Graça Costa; Asad, Nasser Ribeiro; Marin, Pedro Jesus; Bernardo-Filho, Mario

    2017-01-01

    Background: Whole body vibration (WBV) exercise has been used in health sciences. Authors have reported that changes on the concentration of plasma biomarkers could be associated with the WBV effects. The aim of this investigation is to assess the consequences of exposition of 25 Hz mechanical vibration generated in oscillating/vibratory platform (OVP) on the concentration of some plasma biomarkers and on the weight of rats. Materials and Methods: Wistar rats were divided into two groups. The animals of the Experimental Group (EG) were submitted to vibration (25 Hz) generated in an OVP with four bouts of 30 seconds with rest time of 60 seconds between the bouts. This procedure was performed daily for 12 days. The animals of the control group (CG) were not exposed to vibration. Results: Our findings show that the WBV exercise at 25 Hz was not capable to alter significantly (p<0.05) the weight of the rats. A significant alteration in the concentrations of amylase was found. Conclusion: Our results indicate a modulation of the WBV exercise with vibration of 25 Hz of frequency (i) in the pathways related to the weight and (ii) in the concentration of some biomarkers, such as amylase. PMID:28740944

  9. A signal-substrate match in the substrate-borne component of a multimodal courtship display

    Directory of Open Access Journals (Sweden)

    Damian O. ELIAS, Andrew C. MASON, Eileen A. HEBETS

    2010-06-01

    Full Text Available The environment can impose strong limitations on the efficacy of signal transmission. In particular, for vibratory communication, the signaling environment is often extremely heterogeneous at very small scales. Nevertheless, natural selection is expected to select for signals well-suited to effective transmission. Here, we test for substrate-dependent signal efficacy in the wolf spider Schizocosa stridulans Stratton 1991. We first explore the transmission characteristics of this important signaling modality by playing recorded substrate-borne signals through three different substrates (leaf litter, pine litter, and red clay and measuring the propagated signal. We found that the substrate-borne signal of S. stridulans attenuates the least on leaf litter, the substrate upon which the species is naturally found. Next, by assessing mating success with artificially muted and non-muted males across different signaling substrates (leaf litter, pine litter, and sand, we explored the relationship between substrate-borne signaling and substrate for mating success. We found that muted males were unsuccessful in obtaining copulations regardless of substrate, while mating success was dependent on the signaling substrate for non-muted males. For non-muted males, more males copulated on leaf litter than any other substrate. Taken together, these results confirm the importance of substrate-borne signaling in S. stridulans and suggest a match between signal properties and signal efficacy – leaf litter transmits the signal most effectively and males are most successful in obtaining copulations on leaf litter [Current Zoology 56 (3: 370–378, 2010].

  10. Hypoxia perturbs aryl hydrocarbon receptor signaling and CYP1A1 expression induced by PCB 126 in human skin and liver-derived cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Vorrink, Sabine U. [Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA (United States); Department of Radiation Oncology, The University of Iowa, Iowa City, IA (United States); Severson, Paul L. [Department of Pharmacology and Toxicology, The University of Arizona, Tucson, AZ (United States); Kulak, Mikhail V. [Department of Surgery, The University of Iowa, Iowa City, IA (United States); Futscher, Bernard W. [Department of Pharmacology and Toxicology, The University of Arizona, Tucson, AZ (United States); Domann, Frederick E., E-mail: frederick-domann@uiowa.edu [Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA (United States); Department of Radiation Oncology, The University of Iowa, Iowa City, IA (United States); Department of Surgery, The University of Iowa, Iowa City, IA (United States)

    2014-02-01

    The aryl hydrocarbon receptor (AhR) is an important mediator of toxic responses after exposure to xenobiotics including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and dioxin-like polychlorinated biphenyls (PCBs). Activation of AhR responsive genes requires AhR dimerization with the aryl hydrocarbon receptor nuclear translocator (ARNT), a heterodimeric partner also shared by the hypoxia-inducible factor-1α (HIF-1α) protein. TCDD-stimulated AhR transcriptional activity can be influenced by hypoxia; however, it less well known whether hypoxia interferes with AhR transcriptional transactivation in the context of PCB-mediated AhR activation in human cells. Elucidation of this interaction is important in liver hepatocytes which extensively metabolize ingested PCBs and experience varying degrees of oxygen tension during normal physiologic function. This study was designed to assess the effect of hypoxia on AhR transcriptional responses after exposure to 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126). Exposure to 1% O{sub 2} prior to PCB 126 treatment significantly inhibited CYP1A1 mRNA and protein expression in human HepG2 and HaCaT cells. CYP1A1 transcriptional activation was significantly decreased upon PCB 126 stimulation under conditions of hypoxia. Additionally, hypoxia pre-treatment reduced PCB 126 induced AhR binding to CYP1 target gene promoters. Importantly, ARNT overexpression rescued cells from the inhibitory effect of hypoxia on XRE-luciferase reporter activity. Therefore, the mechanism of interference of the signaling crosstalk between the AhR and hypoxia pathways appears to be at least in part dependent on ARNT availability. Our results show that AhR activation and CYP1A1 expression induced by PCB 126 were significantly inhibited by hypoxia and hypoxia might therefore play an important role in PCB metabolism and toxicity. - Highlights: • Significant crosstalk exists between AhR and HIF-1α signaling. • Hypoxia perturbs PCB 126 induced AhR function and

  11. On the Land-Ocean Contrast of Tropical Convection and Microphysics Statistics Derived from TRMM Satellite Signals and Global Storm-Resolving Models

    Science.gov (United States)

    Matsui, Toshihisa; Chern, Jiun-Dar; Tao, Wei-Kuo; Lang, Stephen E.; Satoh, Masaki; Hashino, Tempei; Kubota, Takuji

    2016-01-01

    A 14-year climatology of Tropical Rainfall Measuring Mission (TRMM) collocated multi-sensor signal statistics reveal a distinct land-ocean contrast as well as geographical variability of precipitation type, intensity, and microphysics. Microphysics information inferred from the TRMM precipitation radar and Microwave Imager (TMI) show a large land-ocean contrast for the deep category, suggesting continental convective vigor. Over land, TRMM shows higher echo-top heights and larger maximum echoes, suggesting taller storms and more intense precipitation, as well as larger microwave scattering, suggesting the presence of morelarger frozen convective hydrometeors. This strong land-ocean contrast in deep convection is invariant over seasonal and multi-year time-scales. Consequently, relatively short-term simulations from two global storm-resolving models can be evaluated in terms of their land-ocean statistics using the TRMM Triple-sensor Three-step Evaluation via a satellite simulator. The models evaluated are the NASA Multi-scale Modeling Framework (MMF) and the Non-hydrostatic Icosahedral Cloud Atmospheric Model (NICAM). While both simulations can represent convective land-ocean contrasts in warm precipitation to some extent, near-surface conditions over land are relatively moisture in NICAM than MMF, which appears to be the key driver in the divergent warm precipitation results between the two models. Both the MMF and NICAM produced similar frequencies of large CAPE between land and ocean. The dry MMF boundary layer enhanced microwave scattering signals over land, but only NICAM had an enhanced deep convection frequency over land. Neither model could reproduce a realistic land-ocean contrast in in deep convective precipitation microphysics. A realistic contrast between land and ocean remains an issue in global storm-resolving modeling.

  12. Ligustrazine attenuates the platelet-derived growth factor-BB-induced proliferation and migration of vascular smooth muscle cells by interrupting extracellular signal-regulated kinase and P38 mitogen-activated protein kinase pathways.

    Science.gov (United States)

    Yu, Lifei; Huang, Xiaojing; Huang, Kai; Gui, Chun; Huang, Qiaojuan; Wei, Bin

    2015-07-01

    The abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) leads to intimal thickening of the aorta and is, therefore, important in the development of arteriosclerosis. As a result, the use of antiproliferative and antimigratory agents for VSMCs offers promise for the treatment of vascular disorders. Although several studies have demonstrated that ligustrazine may be used to treat heart and blood vessel diseases, the detailed mechanism underlying its actions remain to be elucidated. In the present study, the inhibitory effect of ligustrazine on platelet-derived growth factor (PDGF)-BB-stimulated VSMC proliferation and migration, and the underlying mechanisms were investigated. The findings demonstrated that ligustrazine significantly inhibited PDGF-BB-stimulated VSMC proliferation. VSMCs dedifferentiated into a proliferative phenotype under PDGF-BB stimulation, which was effectively reversed by the administration of ligustrazine. In addition, ligustrazine also downregulated the production of nitric oxide and cyclic guanine monophosphate, induced by PDGF-BB. Additionally, ligustrazine significantly inhibited PDGF-BB-stimulated VSMC migration. Mechanistic investigation indicated that the upregulation of cell cycle-associated proteins and the activation of the extracellular signal-regulated kinase (ERK) and P38 mitogen-activated protein kinase (MAPK) signaling induced by PDGF-BB was suppressed by the administration of ligustrazine. In conclusion, the present study, demonstrated for the first time, to the best of our knowledge, that ligustrazine downregulated PDGF-BB-induced VSMC proliferation and migration partly, at least, through inhibiting the activation of the ERK and P38 MAPK signaling.

  13. Human Bone Marrow Mesenchymal stromal cell derived Osteoblasts Promote the Expansion of Hematopoietic Progenitors through Beta-Catenin and Notch Signaling Pathways.

    Science.gov (United States)

    Michalicka, Matthew; Boisjoli, Gavin; Jahan, Suria; Hovey, Owen; Doxtator, Emily; Abu-Khader, Ahmad; Pasha, Roya; Pineault, Nicolas

    2017-10-19

    Coculture of hematopoietic stem cells (HSC) with primary stromal cells from HSC niches supports the maintenance and expansion of HSC and progenitors ex vivo. However, a major drawback is the availability of primary human samples for research and clinical applications. We investigated the use of in vitro derived osteoblasts as a new source of feeder cells and characterized the molecular pathways that mediate their growth promoting activities. First, we compared the growth and differentiation modulating activities of mesenchymal stromal cells (MSC)-derived osteoblasts (M-OST) to that of their undifferentiated precursor on umbilical cord blood (UCB) progenitors. Feeder-free cultures were also included as baseline control. Cell growth and expansion of hematopoietic progenitors were significantly enhanced by both feeder cell types. However, progenitor cell growth was considerably greater with M-OST. Coculture also promoted the maintenance of immature CD34+ progenitor subsets and modulated in a positive fashion the expression of several homing-related cell surface receptors, in a feeder-specific fashion. Serial transplantation experiments revealed that M-OST coculture supported the maintenance of long-term lympho-myeloid reconstituting HSC that provided engraftment levels generally superior to that from MSC cocultures. Mechanistically, we found that coculture with M-OST was associated with enhanced -catenin (-Cat) activity in UCB cells and that abrogation of -Cat/TCF activity blunted the growth promoting activity of the M-OST coculture. Conversely, Notch inhibition reduced UCB cell expansion but to a much lesser extent. In conclusion, this study demonstrates that M-OST are excellent feeder cells for HSC and progenitors, and identify key molecular pathways responsible for the growth enhancing activities of osteoblasts on UCB progenitors.

  14. CAF-derived HGF promotes cell proliferation and drug resistance by up-regulating the c-Met/PI3K/Akt and GRP78 signalling in ovarian cancer cells.

    Science.gov (United States)

    Deying, Wei; Feng, Geng; Shumei, Liang; Hui, Zhao; Ming, Liu; Hongqing, Wang

    2017-04-28

    The tumour microenvironment is a highly heterogeneous entity that plays crucial roles in cancer progression. As the most prominent stromal cell types, cancer-associated fibroblasts (CAFs) produce a variety of factors into the tumour microenvironment. In the present study, we firstly isolated CAFs from tumour tissues of the patients with ovarian cancer and demonstrated that the hepatocyte growth factor (HGF) was highly expressed in the supernatants of CAFs. CAF-derived HGF or human recombinant HGF promoted cell proliferation in human ovarian cell lines SKOV3 and HO-8910 cells. Western blotting analysis also showed that CAF-derived HGF or recombinant HGF activated c-Met/phosphoinositide 3-kinase (PI3K)/Akt and glucose-regulated protein 78 (GRP78) signalling pathways in ovarian cancer cells, and these effects could be abrogated by anti-HGF and c-Met inhibitor INCB28060. Moreover, HGF in CAF matrix attenuated paclitaxel (PAC)-caused inhibition of cell proliferation and increase in cell apoptosis through activating c-Met/PI3K/Akt and GRP78 pathways in SKOV3 and HO-8910 cells. The results in vitro were further validated in nude mice. These findings suggest that CAF-derived HGF plays crucial roles in cell proliferation and drug resistance in ovarian cancer cells. © 2017 The Author(s).

  15. Cinnamaldehyde derivative (CB-PIC) sensitizes chemo-resistant cancer cells to drug-induced apoptosis via suppression of MDR1 and its upstream STAT3 and AKT signalling.

    Science.gov (United States)

    Yun, Miyong; Lee, Duckgue; Park, Moon-Nyeo; Kim, Eun-Ok; Sohn, Eun Jung; Kwon, Byung-Mog; Kim, Sung-Hoon

    2015-01-01

    Our group reported that cinnamaldehyde derivative, (E)-4-((2-(3-oxopop-1-enyl)phenoxy)methyl)pyridinium malonic acid (CB-PIC) induced apoptosis in hypoxic SW620 colorectal cancer cells via activation of AMP-activated protein kinase (AMPK) and extracellular signal regulated kinase (ERK). Herein, sensitizing effect of CB-PIC was investigated in resistant cancer cells such as paclitaxel (PT) resistant lung cancer cells (H460/PT), and Adriamycin (Adr) resistant breast cancer (MCF7/Adr) and colon cancer (HCT15/cos) cells. Various drug resistant cell lines were treated with CB-PIC, and the signalling pathway and functional assay were explored by Western blot, Rhodamine assay, FACS, RT-PCR and MTT assay. We found that CB-PIC effectively exerted cytotoxicity, increased sub G1 population and the cleaved form of poly (ADP-ribose) polymerase (PARP) and caspase 9 in drug resistant cancer cells. Furthermore, CB-PIC sensitized resistant cancer cells to adriamycin via downregulation of survival proteins such as survivin, Bcl-xL and Bcl-2, along with MDR1 suppression leading to accumulation of drug in the intracellular region. Of note, CB-PIC transcriptionally decreased MDR1 expression via suppression of STAT3 and AKT signalling in three resistant cancer cells with highly expressed P-glycoprotein. Nonetheless, CB-PIC did not affect transport activity of P-glycoprotein in a short time efflux assay, while epigallocatechin gallate (EGCG) accumulated Rhodamine 123 into intracellular region of cell by direct inhibition of MDR1 transport activity. These data demonstrate that CB-PIC suppresses the P-glycoprotein expression through inhibition of STAT3 and AKT signalling to overcome drug resistance in chemo-resistant cancer cells as a potent chemotherapeutic sensitizer. © 2015 S. Karger AG, Basel.

  16. Paeoniflorin blocks the proliferation of vascular smooth muscle cells induced by platelet‑derived growth factor‑BB through ROS mediated ERK1/2 and p38 signaling pathways.

    Science.gov (United States)

    Fan, Xianwei; Wu, Jintao; Yang, Haitao; Yan, Lijie; Wang, Shanling

    2018-01-01

    The proliferation of vascular smooth muscle cells (VSMCs) contributes to the development of vascular remodeling. In the present study, the effect of paeoniflorin (PAE) on the platelet derived growth factor‑BB (PDGF‑BB)‑induced proliferation of primary cultured rat VSMCs and its molecular mechanism was investigated. The toxicity was determined by the try pan blue exclusion test. Cell proliferation was determined using a CCK‑8 assay, DNA synthesis was assessed by measuring the incorporation of BrdU. Cell cycle progression was determined using PI staining and fluorescence‑activated cell sorting. The level of intracellular reactive oxygen species (ROS) generation was assessed using dichlorodihydro fluorescein diacetate. mRNA expression was determined by reverse transcription quantitative polymerase chain reaction. Changes of p38, JNK, ERK1/2 signaling pathways were determined by western blot analysis. Cell migration was detected by scratch assay. PAE was demonstrated to significantly inhibit VSMC proliferation induced by PDGF‑BB in a dose‑and time‑dependent manner without cell cytotoxicity. Thus, PAE blocked progression through the G0/G1 to Sphase of the cell cycle. Furthermore, inhibition of the cell cycle was associated with the inhibition of them RNA expression of cyclin D1, cyclin E, cyclin dependent kinase (CDK) 4 and CDK2 as well as with increased cyclin dependent kinase inhibitor 1A mRNA expression in PDGF‑BB‑stimulated VSMCs. Further studies showed that the beneficial effect of PAE on blocking VSMCs proliferation was related to the suppression of the ROS‑mediated extra cellular signal‑regulated kinase (ERK)1/2 and p38 signaling pathways, although PAE had no significant effect on the c‑Jun N‑terminal kinase signalling pathway. These results demonstrated that PAE suppressed PDGF‑BB‑induced VSMC proliferation through the ROS‑mediated ERK1/2 and p38 signaling pathways, suggesting that it may be a feasible therapy for vascular

  17. Green tea EGCG enhances cardiac function restoration through expression of survival signaling in DM rats with autologous adipose tissue-derived stem cell.

    Science.gov (United States)

    Chen, Tung-Sheng; Liou, Show-Yih; Kuo, Chia-Hua; Pan, Lung-Fa; Yeh, Yu-Lan; Liou, Jeffery; Padma, V Vijaya; Yao, Chun-Hsu; Kuo, Wei-Wen; Huang, Chih-Yang

    2017-05-25

    The present study tests a hypothesis that cardioprotective effects mediated by autologous adipose-derived stem cells (ADSC) in rats afflicted with insulin-dependent diabetes mellitus (IDDM), may be synergistically enhanced by oral treatment with green tea epigallocatechin gallat (ECCG). Wistar rats were divided into sham, DM, DM+ADSC (autologous transplanted 1x106 cells/rat) and DM+ADSC+E (E, green tea oral administration EGCG). Heart tissues were isolated for all rats and investigations were performed after 2-months treatment. In the groups of sham, DM and DM+ADSC, we can find that DM induces cardiac-dysfunction (sham and DM) and autologous transplantation of ADSC can partially recover cardiac functions (DM and DM+ADSC) in DM rats. Compared to DM+ADSC, significant improvement in cardiac-functions can be observed in DM+ADSC+E in echocardiographic data, histological observations and even in cellular protein expression. Oral administration of green tea EGCG and autologous transplantation of ADSC show synergistically beneficial effects on diabetic cardiacmyopathy in DM rats. Copyright © 2016, Journal of Applied Physiology.

  18. MASM, a Matrine Derivative, Offers Radioprotection by Modulating Lethal Total-Body Irradiation-Induced Multiple Signaling Pathways in Wistar Rats

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    Jianzhong Li

    2016-05-01

    Full Text Available Matrine is an alkaloid extracted from Sophora flavescens Ait and has many biological activities, such as anti-inflammatory, antitumor, anti-fibrosis, and immunosuppressive properties. In our previous studies, the matrine derivative MASM was synthesized and exhibited potent inhibitory activity against liver fibrosis. In this study, we mainly investigated its protection against lethal total-body irradiation (TBI in rats. Administration of MASM reduced the radiation sickness characteristics and increased the 30-day survival of rats before or after lethal TBI. Ultrastructural observation illustrated that pretreatment of rats with MASM significantly attenuated the TBI-induced morphological changes in the different organs of irradiated rats. Gene expression profiles revealed that pretreatment with MASM had a dramatic effect on gene expression changes caused by TBI. Pretreatment with MASM prevented differential expression of 53% (765 genes of 1445 differentially expressed genes induced by TBI. Pathway enrichment analysis indicated that these genes were mainly involved in a total of 21 pathways, such as metabolic pathways, pathways in cancer, and mitogen-activated protein kinase (MAPK pathways. Our data indicated that pretreatment of rats with MASM modulated these pathways induced by TBI, suggesting that the pretreatment with MASM might provide the protective effects on lethal TBI mainly or partially through the modulation of these pathways, such as multiple MAPK pathways. Therefore, MASM has the potential to be used as an effective therapeutic or radioprotective agent to minimize irradiation damages and in combination with radiotherapy to improve the efficacy of cancer therapy.

  19. Altered gp130 signalling ameliorates experimental colitis via myeloid cell-specific STAT3 activation and myeloid-derived suppressor cells

    Science.gov (United States)

    Däbritz, Jan; Judd, Louise M.; Chalinor, Heather V.; Menheniott, Trevelyan R.; Giraud, Andrew S.

    2016-01-01

    STAT3 regulates the expansion of myeloid-derived suppressor cells (MDSCs) during inflammation, infection and cancer. Hyperactivation of STAT3 in gp130757F/F mice is associated with protection from experimental colitis. This study determined mechanisms for this protection and compared this to mice with myeloid-specific STAT3-deficiency (LysMcre/STAT3flox; gp130757F/F LysMcre/STAT3flox). Acute and chronic colitis was induced and colons were removed for histological, mRNA and protein analysis. Cell populations from spleen, mesenteric lymph node and colon were analyzed for different myeloid cell populations using flow cytometry. Functions of MDSCs and LPS-stimulated peritoneal macrophages were further characterized by in vitro and in vivo assays. Here we show that the resistance to experimental colitis in gp130757F/F mice is via myeloid-cell specific STAT3 activation, MDSC expansion and increased production of suppressive and protective cytokines. PMID:26848037

  20. Dual Inhibition of Activin/Nodal/TGF-β and BMP Signaling Pathways by SB431542 and Dorsomorphin Induces Neuronal Differentiation of Human Adipose Derived Stem Cells

    Directory of Open Access Journals (Sweden)

    Vedavathi Madhu

    2016-01-01

    Full Text Available Damage to the nervous system can cause devastating diseases or musculoskeletal dysfunctions and transplantation of progenitor stem cells can be an excellent treatment option in this regard. Preclinical studies demonstrate that untreated stem cells, unlike stem cells activated to differentiate into neuronal lineage, do not survive in the neuronal tissues. Conventional methods of inducing neuronal differentiation of stem cells are complex and expensive. We therefore sought to determine if a simple, one-step, and cost effective method, previously reported to induce neuronal differentiation of embryonic stem cells and induced-pluripotent stem cells, can be applied to adult stem cells. Indeed, dual inhibition of activin/nodal/TGF-β and BMP pathways using SB431542 and dorsomorphin, respectively, induced neuronal differentiation of human adipose derived stem cells (hADSCs as evidenced by formation of neurite extensions, protein expression of neuron-specific gamma enolase, and mRNA expression of neuron-specific transcription factors Sox1 and Pax6 and matured neuronal marker NF200. This process correlated with enhanced phosphorylation of p38, Erk1/2, PI3K, and Akt1/3. Additionally, in vitro subcutaneous implants of SB431542 and dorsomorphin treated hADSCs displayed significantly higher expression of active-axonal-growth-specific marker GAP43. Our data offers novel insights into cell-based therapies for the nervous system repair.

  1. Anti-Cancer Activity of an Osthole Derivative, NBM-T-BMX-OS01: Targeting Vascular Endothelial Growth Factor Receptor Signaling and Angiogenesis

    Science.gov (United States)

    Chiu, Pei-Ting; Ho, Shiau-Jing; Wang, Chi-Han; Chi, Chih-Chin; Huang, Yu-Han; Lee, Cheng-Feng; Li, Ying-Shiuan; Ou, George; Hsu, Ming-Jen

    2013-01-01

    Angiogenesis occurs during tissue growth, development and wound healing. It is also required for tumor progression and represents a rational target for therapeutic intervention. NBM-T-BMX-OS01 (BMX), derived from the semisynthesis of osthole, an active ingredient isolated from Chinese herb Cnidium monnieri (L.) Cuss., was recently shown to enhance learning and memory in rats. In this study, we characterized the anti-angiogenic activities of NBM-T-BMX-OS01 (BMX) in an effort to develop novel inhibitors to suppress angiogenesis and tumor growth. BMX inhibited vascular endothelial growth factor (VEGF)-induced proliferation, migration and endothelial tube formation in human umbilical endothelial cells (HUVECs). BMX also attenuated VEGF-induced microvessel sprouting from aortic rings ex vivo and reduced HCT116 colorectal cancer cells-induced angiogenesis in vivo. Moreover, BMX inhibited the phosphorylation of VEGFR2, FAK, Akt and ERK in HUVECs exposed to VEGF. BMX was also shown to inhibit HCT116 cell proliferation and to suppress the growth of subcutaneous xenografts of HCT116 cells in vivo. Taken together, this study provides evidence that BMX modulates vascular endothelial cell remodeling and leads to the inhibition of tumor angiogenesis. These results also support the role of BMX as a potential drug candidate and warrant the clinical development in the treatment of cancer. PMID:24312323

  2. Anti-cancer activity of an osthole derivative, NBM-T-BMX-OS01: targeting vascular endothelial growth factor receptor signaling and angiogenesis.

    Directory of Open Access Journals (Sweden)

    Hung-Yu Yang

    Full Text Available Angiogenesis occurs during tissue growth, development and wound healing. It is also required for tumor progression and represents a rational target for therapeutic intervention. NBM-T-BMX-OS01 (BMX, derived from the semisynthesis of osthole, an active ingredient isolated from Chinese herb Cnidium monnieri (L. Cuss., was recently shown to enhance learning and memory in rats. In this study, we characterized the anti-angiogenic activities of NBM-T-BMX-OS01 (BMX in an effort to develop novel inhibitors to suppress angiogenesis and tumor growth. BMX inhibited vascular endothelial growth factor (VEGF-induced proliferation, migration and endothelial tube formation in human umbilical endothelial cells (HUVECs. BMX also attenuated VEGF-induced microvessel sprouting from aortic rings ex vivo and reduced HCT116 colorectal cancer cells-induced angiogenesis in vivo. Moreover, BMX inhibited the phosphorylation of VEGFR2, FAK, Akt and ERK in HUVECs exposed to VEGF. BMX was also shown to inhibit HCT116 cell proliferation and to suppress the growth of subcutaneous xenografts of HCT116 cells in vivo. Taken together, this study provides evidence that BMX modulates vascular endothelial cell remodeling and leads to the inhibition of tumor angiogenesis. These results also support the role of BMX as a potential drug candidate and warrant the clinical development in the treatment of cancer.

  3. The platelet-activating factor acetylhydrolase gene derived from Trichoderma harzianum induces maize resistance to Curvularia lunata through the jasmonic acid signaling pathway.

    Science.gov (United States)

    Yu, Chuanjin; Fan, Lili; Gao, Jinxin; Wang, Meng; Wu, Qiong; Tang, Jun; Li, Yaqian; Chen, Jie

    2015-01-01

    Platelet-activating factor acetylhydrolase (PAF-AH) derived from Trichoderma harzianum was upregulated by the interaction of T. harzianum with maize roots or the foliar pathogen Curvularia lunata. PAF-AH was associated with chitinase and cellulase expressions, but especially with chitinase, because its activity in the KO40 transformant (PAF-AH disruption transformant) was lower, compared with the wild-type strain T28. The result demonstrated that the colonization of maize roots by T. harzianum induced systemic protection of leaves inoculated with C. lunata. Such protection was associated with the expression of inducible jasmonic acid pathway-related genes. Moreover, the data from liquid chromatography-mass spectrometry confirmed that the concentration of jasmonic acid in maize leaves was associated with the expression level of defense-related genes, suggesting that PAF-AH induced resistance to the foliar pathogen. Our findings showed that PAF-AH had an important function in inducing systemic resistance to maize leaf spot pathogen.

  4. Distinct Upstream Role of Type I IFN Signaling in Hematopoietic Stem Cell-Derived and Epithelial Resident Cells for Concerted Recruitment of Ly-6Chi Monocytes and NK Cells via CCL2-CCL3 Cascade.

    Directory of Open Access Journals (Sweden)

    Erdenebileg Uyangaa

    Full Text Available Type I interferon (IFN-I-dependent orchestrated mobilization of innate cells in inflamed tissues is believed to play a critical role in controlling replication and CNS-invasion of herpes simplex virus (HSV. However, the crucial regulators and cell populations that are affected by IFN-I to establish the early environment of innate cells in HSV-infected mucosal tissues are largely unknown. Here, we found that IFN-I signaling promoted the differentiation of CCL2-producing Ly-6Chi monocytes and IFN-γ/granzyme B-producing NK cells, whereas deficiency of IFN-I signaling induced Ly-6Clo monocytes producing CXCL1 and CXCL2. More interestingly, recruitment of Ly-6Chi monocytes preceded that of NK cells with the levels peaked at 24 h post-infection in IFN-I-dependent manner, which was kinetically associated with the CCL2-CCL3 cascade response. Early Ly-6Chi monocyte recruitment was governed by CCL2 produced from hematopoietic stem cell (HSC-derived leukocytes, whereas NK cell recruitment predominantly depended on CC chemokines produced by resident epithelial cells. Also, IFN-I signaling in HSC-derived leukocytes appeared to suppress Ly-6Ghi neutrophil recruitment to ameliorate immunopathology. Finally, tissue resident CD11bhiF4/80hi macrophages and CD11chiEpCAM+ dendritic cells appeared to produce initial CCL2 for migration-based self-amplification of early infiltrated Ly-6Chi monocytes upon stimulation by IFN-I produced from infected epithelial cells. Ultimately, these results decipher a detailed IFN-I-dependent pathway that establishes orchestrated mobilization of Ly-6Chi monocytes and NK cells through CCL2-CCL3 cascade response of HSC-derived leukocytes and epithelium-resident cells. Therefore, this cascade response of resident-to-hematopoietic-to-resident cells that drives cytokine-to-chemokine-to-cytokine production to recruit orchestrated innate cells is critical for attenuation of HSV replication in inflamed tissues.

  5. Neuritogenic Monoglyceride Derived from the Constituent of a Marine Fish for Activating the PI3K/ERK/CREB Signalling Pathways in PC12 Cells

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    Wei Yang

    2013-12-01

    Full Text Available A neuritogenic monoglyceride, 1-O-(myristoyl glycerol (MG, was isolated from the head of Ilisha elongate using a PC12 cell bioassay system, and its chemical structure was elucidated using spectroscopic methods. MG significantly induced 42% of the neurite outgrowth of PC12 cells at a concentration of 10 μM. To study the structure-activity relationships of MG, a series of monoglycerides was designed and synthesised. Bioassay results indicated that the alkyl chain length plays a key role in the neuritogenic activity of the monoglycerides. The groups that link the propane-1,2-diol and alkyl chain were also investigated. An ester linkage, rather than an amido one, was found to be optimal for neuritogenic activity. Therefore, 1-O-(stearoyl glycerol (SG, which induces 57% of the neurite outgrowth of PC12 cells at 10 μM, was determined to be a lead compound for neuritogenic activity. We then investigated the mechanism of action of neurite outgrowth induced by SG on PC12 cells using protein specific inhibitors and Western blot analysis. The mitogen-activated kinase/ERK kinase (MEK inhibitor U0126 and the phosphatidylinositol-3 kinase (PI3K inhibitor LY294002 significantly decreased neurite outgrowth. At the same time, SG increased phosphorylation of CREB in protein level. Thus, SG-induced neuritogenic activity depends on the activation of the extracellular-regulated protein kinase (ERK, cAMP responsive element-binding protein (CREB and PI3K signalling pathways in PC12 cells.

  6. Enteroglial-derived S100B protein integrates bacteria-induced Toll-like receptor signalling in human enteric glial cells.

    Science.gov (United States)

    Turco, Fabio; Sarnelli, Giovanni; Cirillo, Carla; Palumbo, Ilaria; De Giorgi, Francesco; D'Alessandro, Alessandra; Cammarota, Marcella; Giuliano, Mariateresa; Cuomo, Rosario

    2014-01-01

    Enteric glial cells (EGC) have been suggested to participate in host-bacteria cross-talk, playing a protective role within the gut. The way EGC interact with microorganisms is still poorly understood. We aimed to evaluate whether: EGC participate in host-bacteria interaction; S100B and Toll-like receptor (TLR) signalling converge in a common pathway leading to nitric oxide (NO) production. Primary cultures of human EGC were exposed to pathogenic (enteroinvasive Escherichia coli; EIEC) and probiotic (Lactobacillus paracasei F19) bacteria. Cell activation was assessed by evaluating the expression of cFos and major histocompatibility complex (MHC) class II molecules. TLR expression in EGC was evaluated at both baseline and after exposure to bacteria by real-time PCR, fluorescence microscopy and western blot analysis. S100B expression and NO release from EGC, following exposure to bacteria, were measured in the presence or absence of specific TLR and S100B pathway inhibitors. EIEC activated EGC by inducing the expression of cFos and MHC II. EGC expressed TLR at baseline. Pathogens and probiotics differentially modulated TLR expression in EGC. Pathogens, but not probiotics, significantly induced S100B protein overexpression and NO release from EGC. Pretreatment with specific inhibitors of TLR and S100B pathways abolished bacterial-induced NO release from EGC. Human EGC interact with bacteria and discriminate between pathogens and probiotics via a different TLR expression and NO production. In EGC, NO release is impaired in the presence of specific inhibitors of the TLR and S100B pathways, suggesting the presence of a novel common pathway involving both TLR stimulation and S100B protein upregulation.

  7. HLA-E: strong association with beta2-microglobulin and surface expression in the absence of HLA class I signal sequence-derived peptides.

    Science.gov (United States)

    Lo Monaco, Elisa; Sibilio, Leonardo; Melucci, Elisa; Tremante, Elisa; Suchànek, Miloslav; Horejsi, Vaclav; Martayan, Aline; Giacomini, Patrizio

    2008-10-15

    The nonclassical class I HLA-E molecule folds in the presence of peptide ligands donated by the signal sequences of permissive class I HLA alleles, with the aid of TAP and tapasin. To identify HLA-E-specific Abs, four monoclonals of the previously described MEM series were screened by isoelectric focusing (IEF) blot and immunoprecipitation/IEF on >30 single-allele class I transfectants and HLA-homozygous B lymphoid cells coexpressing HLA-E and HLA-A, -B, -C, -F, or -G. Despite their HLA-E-restricted reactivity patterns (MEM-E/02 in IEF blot; MEM-E/07 and MEM-E/08 in immunoprecipitation), all of the MEM Abs unexpectedly reacted with beta(2)-microglobulin (beta(2)m)-free and denatured (but not beta(2)m-associated and folded) HLA-E H chains. Remarkably, other HLA-E-restricted Abs were also reactive with free H chains. Immunodepletion, in vitro assembly, flow cytometry, and three distinct surface-labeling methods, including a modified (conformation-independent) biotin-labeling assay, revealed the coexistence of HLA-E conformers with unusual and drastically antithetic features. MEM-reactive conformers were thermally unstable and poorly surface expressed, as expected, whereas beta(2)m-associated conformers were either unstable and weakly reactive with the prototypic conformational Ab W6/32, or exceptionally stable and strongly reactive with Abs to beta(2)m even in cells lacking permissive alleles (721.221), TAP (T2), or tapasin (721.220). Noncanonical, immature (endoglycosidase H-sensitive) HLA-E glycoforms were surface expressed in these cells, whereas mature glycoforms were exclusively expressed (and at much lower levels) in cells carrying permissive alleles. Thus, HLA-E is a good, and not a poor, beta(2)m assembler, and TAP/tapasin-assisted ligand donation is only one, and possibly not even the major, pathway leading to its stabilization and surface expression.

  8. Long-acting genipin derivative protects retinal ganglion cells from oxidative stress models in vitro and in vivo through the Nrf2/antioxidant response element signaling pathway.

    Science.gov (United States)

    Koriyama, Yoshiki; Chiba, Kenzo; Yamazaki, Matsumi; Suzuki, Hirokazu; Muramoto, Ken-ichiro; Kato, Satoru

    2010-10-01

    Previously, we reported that genipin, a herbal iridoid, had neuritogenic and neuroprotective actions on PC12 cells. Although nitric oxide (NO)-activated signalings were proposed to be neuritogenic, the neuroprotective action of genipin remains to be elucidated. From the standpoint of NO activation, we tested a possible protective mechanism through the nitrosative Kelch-like ECH-associated protein (Keap1)/NF-E2-related factor 2 (Nrf2)-antioxidant response element pathway in rat retinal ganglion cells (RGC-5 cells) in culture, and in vivo, against hydrogen peroxide and optic nerve injury (ONI), respectively, using a long-acting (1R)-isoPropyloxygenipin (IPRG001). IPRG001 induced NO generation and the expressions of antioxidative enzymes, such as heme oxygenase-1 (HO-1), in RGC-5 cells. The protective action of IPRG001 depended on HO-1 and NO induction. We found that S-nitrosylation of Keap1 by IPRG001 may contribute to translocation of Nrf2 to the nucleus and triggered transcriptional activation of antioxidative enzymes. Furthermore, apoptotic cells were increased and 4-hydroxy-2-nonenal was accumulated in rat retina following ONI. Pre-treatment with IPRG001 almost completely suppressed apoptosis and accumulation of 4-hydroxy-2-nonenal in RGCs following ONI accompanied by HO-1 induction. These data demonstrate for the first time that IPRG001 exerts neuroprotective action in RGCs in vitro and in vivo, through the Nrf2/antioxidant response element pathway by S-nitrosylation against oxidative stress. © 2010 The Authors. Journal Compilation © 2010 International Society for Neurochemistry.

  9. Synergetic signal amplification based on electrochemical reduced graphene oxide-ferrocene derivative hybrid and gold nanoparticles as an ultra-sensitive detection platform for bisphenol A

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Na; Liu, Meiling, E-mail: liumeilingww@126.com; Li, Haitao; Zhang, Youyu; Yao, Shouzhuo

    2015-01-01

    Highlights: • A novel (4-ferrocenylethyne) phenylamine was firstly covalently grafted onto GO. • The rGO-Fc-NH{sub 2}/AuNPs composite has good conductivity and compatibility. • The nanocomposite effectively prevent the electron mediator leaking from electrode. • A synergetic amplification platform to ultra-sensitive detect BPA was established. - Abstract: In this paper, a novel electro-active graphene oxide (GO) nanocomposite was firstly prepared by covalently grafted (4-ferrocenylethyne) phenylamine (Fc-NH{sub 2}) onto the surface of GO. The synthesized hybridized nanocomposite of GO-Fc-NH{sub 2} coupled with HAuCl{sub 4} simultaneously electrodeposited on the glassy carbon electrodes (GCE) to obtain rGO-Fc-NH{sub 2}/AuNPs/GCE. The covalently grafted material of the rGO-Fc-NH{sub 2}/AuNPs film can effectively prevent the electron mediator leaking from the electrode surface, which can hold the advantage of both the nanomaterials and electron mediator. By employing the catalysis effect of the nanomaterial and electron mediator coupling with large active surface area and high accumulation capacity of rGO-Fc-NH{sub 2}/AuNPs, a synergetic signal amplification platform for ultra-sensitive detection of bisphenol A (BPA) was successfully established. With this novel sensor, the oxidation peak currents of BPA were linearly dependent on the BPA concentrations in the range of 0.005–10 μM with the detection limit of 2 nM. Modification of electron mediators on nanomaterials can greatly enhance the electrochemical performance of the sensors and will provide a new concept for fabricating newly electro-active nanomaterials-based electrochemical biosensors.

  10. Enhanced target-specific signal detection using an Escherichia coli lysate in multiplex microbead immunoassays with E. coli-derived recombinant antigens.

    Science.gov (United States)

    Crestani, Sandra; Leitolis, Amanda; Lima, Lucianna Freitas Oliveira; Krieger, Marco A; Foti, Leonardo

    2016-08-01

    Diverse techniques have been developed to analyze antibody-mediated responses to infections. However, the most common tests, i.e., enzyme-linked immunosorbent assays, require separate reactions for each antigen and consequently necessitate large sample volumes. Luminex technology allows the detection of multiple antibodies in a single experiment, but nonspecific binding can impair the results. Therefore, we examined the use of Escherichia coli lysates to reduce nonspecific binding and improve the results of liquid microarrays based on Luminex technology. Anti-bacteria antibodies were detected in human serum samples, as evidenced by high median fluorescence intensity (MFI) in assays performed with paramagnetic microspheres coupled with E. coli lysates. Moreover, the addition of an E. coli lysate as a blocker reduced the nonspecific binding of antigens produced by E. coli in a concentration-dependent manner. Tris-HCl reduced MFI values in negative samples, but did not affect MFI for positive samples. For microspheres coupled with different antigens, an E. coli lysate blocker significantly improved the fluorescence signals from positive samples. The addition of Tris-HCl and the E. coli lysate induced antigen-specific differences in MFI. This combination of the E. coli lysate blocker and Tris-HCl yielded a statistically significant improvement in MFI in the assays for Chagas disease and hepatitis C virus samples. However, for the Treponema pallidum p47 antigen improvement in MFI was only observed for the preparation with the E. coli blocker at a concentration of 3%. In conclusion, the addition of an E. coli lysate and Tris-HCl to the microarray assay reduced the nonspecific binding of human anti-bacteria antibodies and, therefore, increased the specific MFI. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Differences between winter oilseed rape (Brassica napus L.) cultivars in nitrogen starvation-induced leaf senescence are governed by leaf-inherent rather than root-derived signals

    Science.gov (United States)

    Koeslin-Findeklee, Fabian; Becker, Martin A.; van der Graaff, Eric; Roitsch, Thomas; Horst, Walter J.

    2015-01-01

    Nitrogen (N) efficiency of winter oilseed rape (Brassica napus L.) line-cultivars (cvs.), defined as high grain yield under N limitation, has been primarily attributed to maintained N uptake during reproductive growth (N uptake efficiency) in combination with delayed senescence of the older leaves accompanied with maintained photosynthetic capacity (functional stay-green). However, it is not clear whether genotypic variation in N starvation-induced leaf senescence is due to leaf-inherent factors and/or governed by root-mediated signals. Therefore, the N-efficient and stay-green cvs. NPZ-1 and Apex were reciprocally grafted with the N-inefficient and early-senescing cvs. NPZ-2 and Capitol, respectively and grown in hydroponics. The senescence status of older leaves after 12 days of N starvation assessed by SPAD, photosynthesis and the expression of the senescence-specific cysteine protease gene SAG12-1 revealed that the stay-green phenotype of the cvs. NPZ-1 and Apex under N starvation was primarily under the control of leaf-inherent factors. The same four cultivars were submitted to N starvation for up to 12 days in a time-course experiment. The specific leaf contents of biologically active and inactive cytokinins (CKs) and the expression of genes involved in CK homeostasis revealed that under N starvation leaves of early-senescing cultivars were characterized by inactivation of biologically active CKs, whereas in stay-green cultivars synthesis, activation, binding of and response to biologically active CKs were favoured. These results suggest that the homeostasis of biologically active CKs was the predominant leaf-inherent factor for cultivar differences in N starvation-induced leaf senescence and thus N efficiency. PMID:25944925

  12. Differences between winter oilseed rape (Brassica napus L.) cultivars in nitrogen starvation-induced leaf senescence are governed by leaf-inherent rather than root-derived signals.

    Science.gov (United States)

    Koeslin-Findeklee, Fabian; Becker, Martin A; van der Graaff, Eric; Roitsch, Thomas; Horst, Walter J

    2015-07-01

    Nitrogen (N) efficiency of winter oilseed rape (Brassica napus L.) line-cultivars (cvs.), defined as high grain yield under N limitation, has been primarily attributed to maintained N uptake during reproductive growth (N uptake efficiency) in combination with delayed senescence of the older leaves accompanied with maintained photosynthetic capacity (functional stay-green). However, it is not clear whether genotypic variation in N starvation-induced leaf senescence is due to leaf-inherent factors and/or governed by root-mediated signals. Therefore, the N-efficient and stay-green cvs. NPZ-1 and Apex were reciprocally grafted with the N-inefficient and early-senescing cvs. NPZ-2 and Capitol, respectively and grown in hydroponics. The senescence status of older leaves after 12 days of N starvation assessed by SPAD, photosynthesis and the expression of the senescence-specific cysteine protease gene SAG12-1 revealed that the stay-green phenotype of the cvs. NPZ-1 and Apex under N starvation was primarily under the control of leaf-inherent factors. The same four cultivars were submitted to N starvation for up to 12 days in a time-course experiment. The specific leaf contents of biologically active and inactive cytokinins (CKs) and the expression of genes involved in CK homeostasis revealed that under N starvation leaves of early-senescing cultivars were characterized by inactivation of biologically active CKs, whereas in stay-green cultivars synthesis, activation, binding of and response to biologically active CKs were favoured. These results suggest that the homeostasis of biologically active CKs was the predominant leaf-inherent factor for cultivar differences in N starvation-induced leaf senescence and thus N efficiency. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  13. The impact of the frequency of moderate exercise on memory and brain-derived neurotrophic factor signaling in young adult and middle-aged rats.

    Science.gov (United States)

    Costa, M S; Ardais, A P; Fioreze, G T; Mioranzza, S; Botton, P H S; Souza, D O; Rocha, J B T; Porciúncula, L O

    2012-10-11

    The participation of the brain-derived neurotrophic factor (BDNF) in the benefits of physical exercise on cognitive functions has been widely investigated. Different from voluntary exercise, the effects of treadmill running on memory and BDNF are still controversial. Importantly, the impact of the frequency of physical exercise on memory remains still unknown. In this study, young adult and middle-aged rats were submitted to 8 weeks of treadmill running at moderate intensity and divided into 4 groups of frequency: 0, 1, 3 and 7 days/week. Aversive and recognition memory were assessed as well as the immunocontent of proBDNF, BDNF and tyrosine kinase receptor type B (TrkB) in the hippocampus. Frequencies did not modify memory in young adult animals. The frequency of 1 day/week increased proBDNF and BDNF. All frequencies decreased TrkB immunocontent. Middle-aged animals presented memory impairment along with increased BDNF and downregulation of TrkB receptor. The frequency of 1day/week reversed age-related recognition memory impairment, but worsened the performance in the inhibitory avoidance task. The other frequencies rescued aversive memory, but not recognition memory. None of frequencies altered the age-related increase in the BDNF. Seven days/week decreased proBDNF and there was a trend toward increase in the TrkB by the frequency of 1 day/week. These results support that the frequency and intensity of exercise have a profound impact on cognitive functions mainly in elderly. Thus, the effects of physical exercise on behavior and brain functions should take into account the frequency and intensity. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. Innate immune signaling induces high levels of TC-specific deaminase activity in primary monocyte-derived cells through expression of APOBEC3A isoforms.

    Science.gov (United States)

    Thielen, Beth K; McNevin, John P; McElrath, M Juliana; Hunt, Brook Vander Stoep; Klein, Kevin C; Lingappa, Jaisri R

    2010-09-03

    In HIV-1-infected individuals, G-to-A hypermutation is found in HIV-1 DNA isolated from peripheral blood mononuclear cells (PBMCs). These mutations are thought to result from editing by one or more host enzymes in the APOBEC3 (A3) family of cytidine deaminases, which act on CC (APOBEC3G) and TC (other A3 proteins) dinucleotide motifs in DNA (edited cytidine underlined). Although many A3 proteins display high levels of deaminase activity in model systems, only low levels of A3 deaminase activity have been found in primary cells examined to date. In contrast, here we report high levels of deaminase activity at TC motifs when whole PBMCs or isolated primary monocyte-derived cells were treated with interferon-alpha (IFNalpha) or IFNalpha-inducing toll-like receptor ligands. Induction of TC-specific deaminase activity required new transcription and translation and correlated with the appearance of two APOBEC3A (A3A) isoforms. Knockdown of A3A in monocytes with siRNA abolished TC-specific deaminase activity, confirming that A3A isoforms are responsible for all TC-specific deaminase activity observed. Both A3A isoforms appear to be enzymatically active; moreover, our mutational studies raise the possibility that the smaller isoform results from internal translational initiation. In contrast to the high levels of TC-specific activity observed in IFNalpha-treated monocytes, CC-specific activity remained low in PBMCs, suggesting that A3G deaminase activity is relatively inhibited, unlike that of A3A. Together, these findings suggest that deaminase activity of A3A isoforms in monocytes and macrophages may play an important role in host defense against viruses.

  15. Vam3, a compound derived from Vitis amurensis Rupr., attenuated colitis-related tumorigenesis by inhibiting NF-κB signaling pathway

    Directory of Open Access Journals (Sweden)

    Lingling Xuan

    2016-09-01

    -regulated. In the AOM plus DSS-induced CRC murine model, the Vam3 and DSCG-treated mice had less tumor numbers than those treated with vehicle. Expression of phospho-NF-κB p65, production of inflammatory cytokines, and infiltration of MCs and CD11b+Gr1+ cells were attenuated in the Vam3-treated mice.Conclusions: Vam3 treatment could attenuate the CRC development. This effect may be due to its inhibition on NF-κB signaling pathway in MCs and macrophages of the inflamed intestines.

  16. GYF-21, an Epoxide 2-(2-Phenethyl-Chromone Derivative, Suppresses Innate and Adaptive Immunity via Inhibiting STAT1/3 and NF-κB Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Ran Guo

    2017-05-01

    Full Text Available Multiple sclerosis is a chronic inflammatory autoimmune disease of the central nervous system characterized by demyelinating plaques and axonal loss. Inhibition on over activation of innate and adaptive immunity provides a rationale strategy for treatment of multiple sclerosis. In the present study, we investigated the inhibitory effects of GYF-21, an epoxide 2-(2-phenethyl-chromone derivative isolated from Chinese agarwood, on innate and adaptive immunity for revealing its potential to treat multiple sclerosis. The results showed that GYF-21 markedly inhibited the activation of microglia, and dendritic cells as well as neutrophils, all of which play important roles in innate immunity. Furthermore, GYF-21 significantly suppressed adaptive immunity via inhibiting the differentiation of naive CD4+ T cells into T helper 1 (Th1 and T helper 17 (Th17 cells, and suppressing the activation, proliferation, and IFN-γ secretion of CD8+ T cells. The mechanism study showed that GYF-21 evidently inhibited the activation of STAT1/3 and NF-κB signaling pathways in microglia. In conclusion, we demonstrated that GYF-21 can significantly inhibit innate and adaptive immunity via suppressing STAT1/3 and NF-κB signaling pathways, and has potential to be developed into therapeutic drug for multiple sclerosis.

  17. GYF-21, an Epoxide 2-(2-Phenethyl)-Chromone Derivative, Suppresses Innate and Adaptive Immunity via Inhibiting STAT1/3 and NF-κB Signaling Pathways.

    Science.gov (United States)

    Guo, Ran; Zhao, Yun-Fang; Li, Jun; Gu, Yu-Fan; Huo, Hui-Xia; Li, Shan-Shan; Song, Yue-Lin; Zhu, Zhi-Xiang; Tu, Peng-Fei

    2017-01-01

    Multiple sclerosis is a chronic inflammatory autoimmune disease of the central nervous system characterized by demyelinating plaques and axonal loss. Inhibition on over activation of innate and adaptive immunity provides a rationale strategy for treatment of multiple sclerosis. In the present study, we investigated the inhibitory effects of GYF-21, an epoxide 2-(2-phenethyl)-chromone derivative isolated from Chinese agarwood, on innate and adaptive immunity for revealing its potential to treat multiple sclerosis. The results showed that GYF-21 markedly inhibited the activation of microglia, and dendritic cells as well as neutrophils, all of which play important roles in innate immunity. Furthermore, GYF-21 significantly suppressed adaptive immunity via inhibiting the differentiation of naive CD4+ T cells into T helper 1 (Th1) and T helper 17 (Th17) cells, and suppressing the activation, proliferation, and IFN-γ secretion of CD8+ T cells. The mechanism study showed that GYF-21 evidently inhibited the activation of STAT1/3 and NF-κB signaling pathways in microglia. In conclusion, we demonstrated that GYF-21 can significantly inhibit innate and adaptive immunity via suppressing STAT1/3 and NF-κB signaling pathways, and has potential to be developed into therapeutic drug for multiple sclerosis.

  18. Antiaging Properties of a Grape-Derived Antioxidant Are Regulated by Mitochondrial Balance of Fusion and Fission Leading to Mitophagy Triggered by a Signaling Network of Sirt1-Sirt3-Foxo3-PINK1-PARKIN

    Directory of Open Access Journals (Sweden)

    Somak Das

    2014-01-01

    Full Text Available It was proposed that resveratrol, a polyphenolic antioxidant and a calorie restriction mimetic could promote longevity but subsequent studies could not prove this. The original proposal was based on the fact that a grape-derived antioxidant could activate the antiaging gene Sirt1. Most studies agree that indeed grape activates Sirt1, but a question remains whether Sirt1 is the cause or consequence of resveratrol treatment. Subsequently, mitochondrial Sirt3 was found to be activated. The present study on ischemic reperfusion (I/R in rat hearts demonstrates that Foxo3a is activated subsequent to Sirt3 activation, which then activates PINK1. PINK1 potentiates activation of PARKIN leading to the activation of mitochondrial fission and mitophagy. Confocal microscopy conclusively shows the coexistence of Sirt3 with Foxo3a and Foxo3a with PINK1 and PARKIN. Mitophagy was demonstrated both by confocal microscopy and transmission electron microscopy. Western blot analyses data are consistent with the results of confocal microscopy. It appears that the grape-derived antioxidant modifies the intracellular environment by changing the oxidizing milieu into a reducing milieu and upregulating intracellular glutathione, potentiates a signal transduction cascade consisting of Sirt1/Sirt3-Foxo3a-PINK1-PARKIN-mitochondrial fusion fission-mitophagy that leads to cardioprotection, and paves the way to an anti-aging environment.

  19. Epithelial cell-derived periostin functions as a tumor suppressor in gastric cancer through stabilizing p53 and E-cadherin proteins via the Rb/E2F1/p14ARF/Mdm2 signaling pathway.

    Science.gov (United States)

    Lv, Hongjun; Liu, Rui; Fu, Jiao; Yang, Qi; Shi, Jing; Chen, Pu; Ji, Meiju; Shi, Bingyin; Hou, Peng

    2014-01-01

    Periostin is usually considered as an oncogene in diverse human cancers, including breast, prostate, colon, esophagus, and pancreas cancers, whereas it acts as a tumor suppressor in bladder cancer. In gastric cancer, it has been demonstrated that periglandular periostin expression is decreased whereas stromal periostin expression is significantly increased as compared with normal gastric tissues. Moreover, periostin produced by stromal myofibroblasts markedly promotes gastric cancer cell growth. These observations suggest that periostin derived from different types of cells may play distinct biological roles in gastric tumorigenesis. The aim of this study was to explore the biological functions and related molecular mechanisms of epithelial cell-derived periostin in gastric cancer. Our data showed that periglandular periostin was significantly down-regulated in gastric cancer tissues as compared with matched normal gastric mucosa. In addition, its expression in metastatic lymph nodes was significantly lower than that in their primary cancer tissues. Our data also demonstrated that periglandular periostin expression was negatively associated with tumor stage. More importantly, restoration of periostin expression in gastric cancer cells dramatically suppressed cell growth and invasiveness. Elucidation of the mechanisms involved revealed that periostin restoration enhanced Rb phosphorylation and sequentially activated the transcription of E2F1 target gene p14(ARF), leading to Mdm2 inactivation and the stabilization of p53 and E-cadherin proteins. Strikingly, these effects of periostin were abolished upon Rb deletion. Collectively, we have for the first time demonstrated that epithelial cell-derived periostin exerts tumor-suppressor activities in gastric cancer through stabilizing p53 and E-cadherin proteins via the Rb/E2F1/p14(ARF)/Mdm2 signaling pathway.

  20. Theanine from tea and its semi-synthetic derivative TBrC suppress human cervical cancer growth and migration by inhibiting EGFR/Met-Akt/NF-κB signaling.

    Science.gov (United States)

    Liu, Jiannan; Sun, Yuping; Zhang, Huarong; Ji, Dexin; Wu, Fei; Tian, Huihui; Liu, Kun; Zhang, Ying; Wu, Benhao; Zhang, Guoying

    2016-11-15

    Cervical cancer is the third most prevalent cancer among women worldwide. Theanine from tea and its derivatives show some anticancer activities. However, the role of theanine and its derivatives against human cervical cancer and the molecular mechanisms of action remain unclear. Thus, in this study, we aim to investigate the anticancer activities and underlying mechanisms of theanine and a theanine derivative, ethyl 6-bromocoumarin-3- carboxylyl L-theanine (TBrC), against human cervical cancer. In vitro and in vivo assays for cancer cell growth and migration have confirmed the inhibition of the cell growth and migration by TBrC and theanine in highly-metastatic human cervical cancer. TBrC displays much stronger activity than theanine on inhibition of the cell growth and migration as well as induction of apoptosis and regulation of related protein expressions in the human cervical cancer cells. TBrC and theanine greatly reduced endogenous and exogenous factors-stimulated cell migration and completely repressed HGF- and EGF+HGF-activated EGFR/Met-Akt/NF-κB signaling by reducing the phosphorylation and expressions of EGFR, Met, Akt, and NF-κB in cervical cancer cells. The enhancer of zeste homolog 2 (EZH2) knockdown decreased the cancer cell migration and NF-κB expression. The NF-κB knockdown reduced the cancer cell migration. TBrC and theanine reduced the EZH2 expression by more than 80%. In addition, TBrC and theanine significantly suppressed human cervical tumor growth in tumor-bearing nude mice without toxicity to the mice. Our results suggest that TBrC and theanine may have the potentials of the therapeutic and/or adjuvant therapeutic application in the treatment of human cervical cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Sulforaphane inhibits platelet-derived growth factor-induced vascular smooth muscle cell proliferation by targeting mTOR/p70S6kinase signaling independent of Nrf2 activation.

    Science.gov (United States)

    Shawky, Noha M; Segar, Lakshman

    2017-05-01

    Activation of nuclear factor erythroid 2-related factor 2 (Nrf2, a transcription factor) and/or inhibition of mammalian target of rapamycin (mTOR) are implicated in the suppression of vascular smooth muscle cell (VSMC) proliferation. The present study has examined the likely regulatory effects of sulforaphane (SFN, an antioxidant) on Nrf2 activation and platelet-derived growth factor (PDGF)-induced mTOR signaling in VSMCs. Using human aortic VSMCs, nuclear extraction and siRNA-mediated downregulation studies were performed to determine the role of Nrf2 on SFN regulation of PDGF-induced proliferative signaling. Immunoprecipitation and/or immunoblot studies were carried out to determine how SFN regulates PDGF-induced mTOR/p70S6K/S6 versus ERK and Akt signaling. Immunohistochemical analysis was performed to determine SFN regulation of S6 phosphorylation in the injured mouse femoral artery. SFN (5μM) inhibits PDGF-induced activation of mTOR without affecting mTOR association with raptor in VSMCs. While SFN inhibits PDGF-induced phosphorylation of p70S6K and 4E-BP1 (downstream targets of mTOR), it does not affect ERK or Akt phosphorylation. In addition, SFN diminishes exaggerated phosphorylation of S6 ribosomal protein (a downstream target of p70S6K) in VSMCs in vitro and in the neointimal layer of injured artery in vivo. Although SFN promotes Nrf2 accumulation to upregulate cytoprotective genes (e.g., heme oxygenase-1 and thioredoxin-1), downregulation of endogenous Nrf2 by target-specific siRNA reveals an Nrf2-independent effect for SFN-mediated inhibition of mTOR/p70S6K/S6 signaling and suppression of VSMC proliferation. Strategies that utilize local delivery of SFN at the lesion site may limit restenosis after angioplasty by targeting mTOR/p70S6K/S6 axis in VSMCs independent of Nrf2 activation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Penile vibratory stimulation yields increased spermatozoa and accessory gland production compared with rectal electroejaculation in a neurologically intact primate (Saimiri boliviensis).

    Science.gov (United States)

    Yeoman, R R; Sonksen, J; Gibson, S V; Rizk, B M; Abee, C R

    1998-09-01

    Assisted reproductive techniques require an efficient semen collection procedure in cases of ejaculatory dysfunction. Anejaculation may be of psychogenic or neurogenic origin but can be overcome with stimulatory techniques. Penile vibratory stimulation (PVS) therapy for anejaculation has recently emerged as an alternative to rectal probe electroejaculation (RPE) and more invasive testicular procedures. Comparison of the stimulatory procedures in neurologically intact subjects is not ethically possible due to the discomfort involved with electroejaculation, and comparison in spinal cord injured men may be compromised due to the intricate effects of chronic denervation on semen quality. We have previously shown the efficacy of PVS in a non-human primate, the squirrel monkey. A cross-over study design comparing semen collected by PVS and RPE was employed during the breeding season in which 15 donor males were divided into two groups. One group received PVS and the other RPE, then, three days later, treatments were reversed. Twelve of 15 animals responded to PVS (80%), all with spermatozoa in the ejaculate. Mean volume (436 +/- 90 microl), motility (80.6 +/- 4.3%), and total spermatozoa (32.8 +/- 10.2 x 10(6)) were significantly higher than in the semen after RPE. RPE resulted in ejaculation in all 15 animals with a semen volume of 205 +/- 25 microl, but fewer samples contained spermatozoa (9/15) resulting in a low total count (0.5 +/- 0.3 x 10(6)). The motility was reduced in those samples with spermatozoa (n = 9; 44.1 +/- 11.4%). Additionally, accessory gland activity was measured via the seminal vesicle and prostrate markers, fructose and citric acid, respectively. The PVS specimens had significantly more fructose (2.9 +/- 0.7 mg/ejaculate) and citric acid (0.46 +/- 0.14 mg/ejaculate) compared to RPE collected specimens (1.2 +/- 0.3 mg/ejaculate and 0.24 +/- 0.04 mg/ejaculate, respectively). In conclusion, PVS produces a much greater sperm yield and increased

  3. A novel berbamine derivative inhibits cell viability and induces apoptosis in cancer stem-like cells of human glioblastoma, via up-regulation of miRNA-4284 and JNK/AP-1 signaling.

    Directory of Open Access Journals (Sweden)

    Fan Yang

    Full Text Available Glioblastoma (GBM is the most common primary brain tumor, accounting for approximately 40% of all central nervous system malignancies. Despite standard treatment consisting of surgical resection, radiotherapy and/or chemotherapy, the prognosis for GBM is poor; with a median survival of 14.6 months. The cancer stem cell or cancer-initiating cell model has provided a new paradigm for understanding development and recurrence of GBM following treatment. Berbamine (BBM is a natural compound derived from the Berberis amurensis plant, and along with its derivatives, has been shown to exhibit antitumor activity in several cancers. Here, we reported that a novel synthetic Berbamine derivative, BBMD3, inhibits cell viability and induces apoptosis of cancer stem-like cells (CSCs in a time- and dose-dependent manner when the CSCs from four GBM patients (PBT003, PBT008, PBT022, and PBT030 were cultured. These CSCs grew in neurospheres and expressed CD133 and nestin as markers. Treatment with BBMD3 destroyed the neurosphere morphology, and led to the induction of apoptosis in the CSCs. Induction of apoptosis in these CSCs is dependent upon activation of caspase-3 and cleavage of poly (ADP-ribose polymerase (PARP. MicroRNA-4284 (miR-4284 was shown to be over-expressed about 4-fold in the CSCs following BBMD3 treatment. Furthermore, transfection of synthetic anti-sense oligonucleotide against human miR-4284 partially blocked the anticancer effects of BBMD3 on the GBM derived CSCs. BBMD3 also increased phosphorylation of the c-Jun N-terminal kinase (JNK/stress-activated protein kinase (SAPK, resulting in an increase expression of phosphorylated c-Jun and total c-Fos; the major components of transcriptional factor AP-1. The JNK-c-Jun/AP-1 signaling pathway plays an important role in the induction of apoptosis in response to UV irradiation and some drug treatments. Targeting glioblastoma stem-like cells with BBMD3 is therefore novel, and may have promise as an

  4. Signal Words

    Science.gov (United States)

    SIGNAL WORDS TOPIC FACT SHEET NPIC fact sheets are designed to answer questions that are commonly asked by the ... making decisions about pesticide use. What are Signal Words? Signal words are found on pesticide product labels, ...

  5. Enhancement of osteogenic differentiation of rat adipose tissue-derived mesenchymal stem cells by zinc sulphate under electromagnetic field via the PKA, ERK1/2 and Wnt/β-catenin signaling pathways.

    Directory of Open Access Journals (Sweden)

    Ezzatollah Fathi

    Full Text Available Zinc ion as an essential trace element and electromagnetic fields (EMFs has been reported to be involved in the regulation of bone metabolism. The aim of this study was to elucidate the effects of zinc sulphate (ZnSO4 on the osteogenic differentiation of adipose tissue-derived mesenchymal stem cells (ADSCs in the presence of EMF as a strategy in osteoporosis therapy. Alkaline phophatase (ALP activity measurement, calcium assay and expression of several osteoblastic marker genes were examined to assess the effect of ZnSO4 on the osteogenic differentiation of ADSCs under EMF. The expression of cAMP and PKA was evaluated by ELISA. The expression of β-catenin, Wnt1, Wnt3a, low-density lipoprotein receptor-related protein 5 (LRP5 and reduced dickkopf1 (DKK1 genes were used to detect the Wnt/β-catenin pathway. It was found that ZnSO4, in the presence of EMF, resulted in an increase in the expression of osteogenic genes, ALP activity and calcium levels. EMF, in the presence of ZnSO4, increased the cAMP level and protein kinase A (PKA activity. Treatment of ADSCs with (MAPK/ERK kinase 1/2 inhibitor, or PKA inhibitor, significantly inhibited the promotion of osteogenic markers, indicating that the induction of osteogenesis was dependent on the ERK and PKA signaling pathways. Real-time PCR analysis showed that ZnSO4, in the presence of EMF, increased the mRNA expressions of β-catenin, Wnt1, Wnt3a, LRP5 and DKK1. In this study, it was shown that 0.432 μg/ml ZnSO4, in the presence of 50 Hz, 20 mT EMF, induced the osteogenic differentiation of ADSCs via PKA, ERK1/2 and Wnt/β-catenin signaling pathways.

  6. A novel synthetic derivative of quercetin, 8-trifluoromethyl-3,5,7,3′,4′-O-pentamethyl-quercetin, inhibits bladder cancer growth by targeting the AMPK/mTOR signaling pathway

    Science.gov (United States)

    Tao, Ting; He, Caimei; Deng, Jun; Huang, Yanjun; Su, Qiongli; Peng, Mei; Yi, Meiling; Darko, Kwame Oteng; Zou, Hui; Yang, Xiaoping

    2017-01-01

    Quercetin is a naturally existing compound and shows attractive anticancer properties for a variety of solid tumors including glioma, bladder cancer, hepatocellular carcinoma, breast cancer, hematological malignancies and prostate carcinoma. However, these anticancer properties have not been clinically approved due to unclear mechanistic information and its low bioactivity. In our previous study, we elucidated that quercetin activates AMPK pathway which is the major mechanism for its unique anticancer effect in bladder cancer. In the present study, we are trying to enhance its bioactivity by chemical modification using fluorination approach to prepare novel chemical entities, based on the principle of intermediate derivative method (IDM). The compound we obtained is named 8-trifluoromethyl-3,5,7,3′,4′-O-pentamethyl- quercetin (TFQ), characterized by NMR spectra and mass spectrum (MS). The results from MTT and cologenic assay in two human and one murine bladder cancer cell lines showed that TFQ exhibits more potent inhibition on the three bladder cancer cell lines than quercetin (Que) although this enhanced effects is not very dramatic. Furthermore, we found that the survival of normal bladder cells PEBC was not significantly suppressed by TFQ compared with Que. Western blot analysis showed that TFQ possess more potent AMPK activation than Que. The downstream of AMPK was further examined by western blot. TFQ treatment is able to inactivate mTOR signaling pathway with the regulation of mTOR, 4EBP1 and P70S6K. These results demonstrated that the fluorinated quercetin derivative TFQ inhibits bladder cancer cell growth through the AMPK/mTOR pathway. Altogether, our findings suggest that TFQ could serve as a new potential therapeutic agent for bladder cancer more effective than Que. PMID:29069736

  7. Analysis of Vibratory Driven Pile.

    Science.gov (United States)

    1987-10-01

    DF ) . Deiier. CO.I Smioak. F)ctl er. ( (C (odite IS. Port IlierICeme. (A; (odeC 155. Port I Iienemeri. (A..: COdIC 156. P’oll F Ficiciiic. (NA...23C;~.i~ ode F)LNA OF19424(1.\\ N i’i nu, toil. F C: ocO’’lK \\;~i~oi .(d ( CGARF R&D(’ Fijbrir\\. (irotoit CI( (I INWI, IANI COdIC S.31F, Norfolk.V

  8. Effects of curcumin (Curcuma longa) on learning and spatial memory as well as cell proliferation and neuroblast differentiation in adult and aged mice by upregulating brain-derived neurotrophic factor and CREB signaling.

    Science.gov (United States)

    Nam, Sung Min; Choi, Jung Hoon; Yoo, Dae Young; Kim, Woosuk; Jung, Hyo Young; Kim, Jong Whi; Yoo, Miyoung; Lee, Sanghee; Kim, Chul Jung; Yoon, Yeo Sung; Hwang, In Koo

    2014-06-01

    Aging is a progressive process, and it may lead to the initiation of neurological diseases. In this study, we investigated the effects of wild Indian Curcuma longa using a Morris water maze paradigm on learning and spatial memory in adult and D-galactose-induced aged mice. In addition, the effects on cell proliferation and neuroblast differentiation were assessed by immunohistochemistry for Ki67 and doublecortin (DCX) respectively. The aging model in mice was induced through the subcutaneous administration of D-galactose (100 mg/kg) for 10 weeks. C. longa (300 mg/kg) or its vehicle (physiological saline) was administered orally to adult and D-galactose-treated mice for the last three weeks before sacrifice. The administration of C. longa significantly shortened the escape latency in both adult and D-galactose-induced aged mice and significantly ameliorated D-galactose-induced reduction of cell proliferation and neuroblast differentiation in the subgranular zone of hippocampal dentate gyrus. In addition, the administration of C. longa significantly increased the levels of phosphorylated CREB and brain-derived neurotrophic factor in the subgranular zone of dentate gyrus. These results indicate that C. longa mitigates D-galactose-induced cognitive impairment, associated with decreased cell proliferation and neuroblast differentiation, by activating CREB signaling in the hippocampal dentate gyrus.

  9. Sesquiterpenoids from the Root of Panax ginseng Attenuates Lipopolysaccharide-Induced Depressive-Like Behavior through the Brain-Derived Neurotrophic Factor/Tropomyosin-Related Kinase B and Sirtuin Type 1/Nuclear Factor-κB Signaling Pathways.

    Science.gov (United States)

    Wang, Weidong; Liu, Xiaofeng; Liu, Jinping; Cai, Enbo; Zhao, Yan; Li, Haijun; Zhang, Lianxue; Li, Pingya; Gao, Yugang

    2018-01-10

    The previous study indicated sesquiterpenoids from the root of Panax ginseng (SPG) exhibited a significant antidepressant-like effect, which might be mediated by the modification of the dopaminergic, GABAergic, and glutamatergic systems. This study was to investigate antidepressant effects and mechanisms on the lipopolysaccharide (LPS)-induced depression-like behavior of SPG. In the tail suspension test (TST) and forced swimming test (FST), SPG (0.25 and 1 mg/kg, i.g.) and fluoxetine (20 mg/kg, i.p.) effectively reduced the immobility time. SPG treatment significantly reduced serum levels of IL-6 and TNF-α and increased suppressed superoxide dismutase (SOD) activity in the hippocampus. In addition, SPG effectively upregulated the brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB), and sirtuin type 1 (Sirt 1) expression in the hippocampus and downregulated the inhibitor of κB-α (IκB-α) and nuclear factor-κB (NF-κB) phosphorylation. These results suggested that SPG exhibited an antidepressant-like effect through the BDNF/TrkB and Sirt 1/NF-κB signaling pathways.

  10. A simple iterative independent component analysis algorithm for vibration source signal identification of complex structures

    Directory of Open Access Journals (Sweden)

    Dong-Sup Lee

    2015-01-01

    Full Text Available Independent Component Analysis (ICA, one of the blind source separation methods, can be applied for extracting unknown source signals only from received signals. This is accomplished by finding statistical independence of signal mixtures and has been successfully applied to myriad fields such as medical science, image processing, and numerous others. Nevertheless, there are inherent problems that have been reported when using this technique: insta- bility and invalid ordering of separated signals, particularly when using a conventional ICA technique in vibratory source signal identification of complex structures. In this study, a simple iterative algorithm of the conventional ICA has been proposed to mitigate these problems. The proposed method to extract more stable source signals having valid order includes an iterative and reordering process of extracted mixing matrix to reconstruct finally converged source signals, referring to the magnitudes of correlation coefficients between the intermediately separated signals and the signals measured on or nearby sources. In order to review the problems of the conventional ICA technique and to vali- date the proposed method, numerical analyses have been carried out for a virtual response model and a 30 m class submarine model. Moreover, in order to investigate applicability of the proposed method to real problem of complex structure, an experiment has been carried out for a scaled submarine mockup. The results show that the proposed method could resolve the inherent problems of a conventional ICA technique.

  11. Damage Based Analysis (DBA) - Theory, Derivation and Practical Application Using Both an Acceleration and Pseudo Velocity Approach

    Science.gov (United States)

    Grillo, Vince

    2017-01-01

    The objective of this presentation is to give a brief overview of the theory behind the (DBA) method, an overview of the derivation and a practical application of the theory using the Python computer language. The Theory and Derivation will use both Acceleration and Pseudo Velocity methods to derive a series of equations for processing by Python. We will take the results and compare both Acceleration and Pseudo Velocity methods and discuss implementation of the Python functions. Also, we will discuss the efficiency of the methods and the amount of computer time required for the solution. In conclusion, (DBA) offers a powerful method to evaluate the amount of energy imparted into a system in the form of both Amplitude and Duration during qualification testing and flight environments. Many forms of steady state and transient vibratory motion can be characterized using this technique. (DBA) provides a more robust alternative to traditional methods such Power Spectral Density (PSD) using a maximax approach.

  12. Damage Based Analysis (DBA): Theory, Derivation and Practical Application - Using Both an Acceleration and Pseudo-Velocity Approach

    Science.gov (United States)

    Grillo, Vince

    2016-01-01

    The objective of this presentation is to give a brief overview of the theory behind the (DBA) method, an overview of the derivation and a practical application of the theory using the Python computer language. The Theory and Derivation will use both Acceleration and Pseudo Velocity methods to derive a series of equations for processing by Python. We will take the results and compare both Acceleration and Pseudo Velocity methods and discuss implementation of the Python functions. Also, we will discuss the efficiency of the methods and the amount of computer time required for the solution. In conclusion, (DBA) offers a powerful method to evaluate the amount of energy imparted into a system in the form of both Amplitude and Duration during qualification testing and flight environments. Many forms of steady state and transient vibratory motion can be characterized using this technique. (DBA) provides a more robust alternative to traditional methods such Power Spectral Density (PSD) using a Maximax approach.

  13. Hemoglobin derivatives

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003371.htm Hemoglobin derivatives To use the sharing features on this page, please enable JavaScript. Hemoglobin derivatives are altered forms of hemoglobin . Hemoglobin is ...

  14. [Effect of alpha-conotoxin MII and its N-terminal derivatives on Ca2+ and Na+ signals induced by nicotine in neuroblastoma cell line SH-SY5Y].

    Science.gov (United States)

    Surin, A M; Kriukova, E V; Strukov, A S; Zhmak, M N; Talka, R; Tuominen, R; Salminen, O; Khiroug, L; Kasheverov, I E; Tsetlin, V I

    2012-01-01

    Nicotinic acetylcholine receptors (nAChRs) are implicated in the regulation ofintracellular Ca2+-dependent processes in cells both in normal and pathological states, alpha-Conotoxins isolated from Conus snails venom are a valuable tool for the study of pharmacological properties and functional role of nAChRs. In the present study the alpha-conotoxin MII analogue with the additional tyrosine attached to the N terminus (Y0-MII) was prepared. Also we synthesized analogs with the N-terminal glycine residue labeled with the Bolton- Hunter reagent (BH-MII) or fluorestsein isothiocyanate (FITC-MII). Fluorescence microscopy studies of the neuroblastoma SH-SY5Y cells loaded with Ca2+ indicator Fura-2 or with Ca2+ and Na+ indicators Fluo-4 and SBFI were performed to examine effect of MII modification on its ability to inhibit nicotin-induced increases in intracellular free Ca2+ and Na+ concentrations ([Ca2+] and [Na+]i respectively). Monitoring of individual cell [Ca2+]i and [Na+]i signals revealed different kinetics of [Ca2+]i and [Na+]i rise and decay in responses to brief nicotine (Nic) applications (10-30 microM, 3-5 min), which indicates to different mechanisms of Ca2+ and Na+ homeostasis control in SH-SY5Y cells. MII inhibited in concentration-dependent manner the both [Ca2+]i and [Na+]i increase induced by Nic. Additional tyrosine in the Y0-MII or, especially, more sizeable label in FITC-MII significantly reduced the inhibitory effect of MII. Whereas the efficiency of the Ca2+ response inhibition by BH-MII was found to be close to the efficiency of its inhibition by natural alpha-conotoxin MII, radioiodinated derivatives BH-MII can be used in radioligand assay.

  15. Target protein interactions of indole-3-carbinol and the highly potent derivative 1-benzyl-I3C with the C-terminal domain of human elastase uncouples cell cycle arrest from apoptotic signaling.

    Science.gov (United States)

    Aronchik, Ida; Chen, Tony; Durkin, Kathleen A; Horwitz, Marshall S; Preobrazhenskaya, Maria N; Bjeldanes, Leonard F; Firestone, Gary L

    2012-11-01

    Elastase is the only currently identified target protein for indole-3-carbinol (I3C), a naturally occurring hydrolysis product of glucobrassicin in cruciferous vegetables such as broccoli, cabbage, and Brussels sprouts that induces a cell cycle arrest and apoptosis of human breast cancer cells. In vitro elastase enzymatic assays demonstrated that I3C and at lower concentrations its more potent derivative 1-benzyl-indole-3-carbinol (1-benzyl-I3C) act as non-competitive allosteric inhibitors of elastase activity. Consistent with these results, in silico computational simulations have revealed the first predicted interactions of I3C and 1-benzyl-I3C with the crystal structure of human neutrophil elastase, and identified a potential binding cluster on an external surface of the protease outside of the catalytic site that implicates elastase as a target protein for both indolecarbinol compounds. The Δ205 carboxyterminal truncation of elastase, which disrupts the predicted indolecarbinol binding site, is enzymatically active and generates a novel I3C resistant enzyme. Expression of the wild type and Δ205 elastase in MDA-MB-231 human breast cancer cells demonstrated that the carboxyterminal domain of elastase is required for the I3C and 1-benzyl-I3C inhibition of enzymatic activity, accumulation of the unprocessed form of the CD40 elastase substrate (a tumor necrosis factor receptor family member), disruption of NFκB nuclear localization and transcriptional activity, and induction of a G1 cell cycle arrest. Surprisingly, expression of the Δ205 elastase molecule failed to reverse indolecarbinol stimulated apoptosis, establishing an elastase-dependent bifurcation point in anti-proliferative signaling that uncouples the cell cycle and apoptotic responses in human breast cancer cells. Copyright © 2011 Wiley Periodicals, Inc.

  16. Detection of signals in noise

    CERN Document Server

    Whalen, Anthony D; Declaris, Nicholas

    1971-01-01

    Detection of Signals in Noise serves as an introduction to the principles and applications of the statistical theory of signal detection. The book discusses probability and random processes; narrowband signals, their complex representation, and their properties described with the aid of the Hilbert transform; and Gaussian-derived processes. The text also describes the application of hypothesis testing for the detection of signals and the fundamentals required for statistical detection of signals in noise. Problem exercises, references, and a supplementary bibliography are included after each c

  17. Signals and systems with MATLAB

    CERN Document Server

    Yang, Won Young; Song, Ik H; Cho, Yong S

    2009-01-01

    Covers some of the theoretical foundations and mathematical derivations that can be used in higher-level related subjects such as signal processing, communication, and control, minimizing the mathematical difficulty and computational burden. This book illustrates the usage of MATLAB and Simulink for signal and system analysis and design.

  18. Vibrotactile Identification of Signal-Processed Sounds from Environmental Events Presented by a Portable Vibrator: A Laboratory Study

    Directory of Open Access Journals (Sweden)

    Parivash Ranjbar

    2008-09-01

    Full Text Available Objectives: To evaluate different signal-processing algorithms for tactile identification of environmental sounds in a monitoring aid for the deafblind. Two men and three women, sensorineurally deaf or profoundly hearing impaired with experience of vibratory experiments, age 22-36 years. Methods: A closed set of 45 representative environmental sounds were processed using two transposing (TRHA, TR1/3 and three modulating algorithms (AM, AMFM, AMMC and presented as tactile stimuli using a portable vibrator in three experiments. The algorithms TRHA, TR1/3, AMFM and AMMC had two alternatives (with and without adaption to vibratory thresholds. In Exp. 1, the sounds were preprocessed and directly fed to the vibrator. In Exp. 2 and 3, the sounds were presented in an acoustic test room, without or with background noise (SNR=+5 dB, and processed in real time. Results: In Exp. 1, Algorithm AMFM and AMFM(A consistently had the lowest identification scores, and were thus excluded in Exp. 2 and 3. TRHA, AM, AMMC, and AMMC(A showed comparable identification scores (30%-42% and the addition of noise did not deteriorate the performance. Discussion: Algorithm TRHA, AM, AMMC, and AMMC(A showed good performance in all three experiments and were robust in noise they can therefore be used in further testing in real environments.

  19. Plant cytokinin signalling.

    Science.gov (United States)

    Keshishian, Erika A; Rashotte, Aaron M

    2015-01-01

    Cytokinin is an essential plant hormone that is involved in a wide range of plant growth and developmental processes which are controlled through its signalling pathway. Cytokinins are a class of molecules that are N(6)-substituted adenine derivatives, such as isopentenyl adenine, and trans- and cis-zeatin, which are common in most plants. The ability to perceive and respond to cytokinin occurs through a modified bacterial two-component pathway that functions via a multi-step phosphorelay. This cytokinin signalling process is a crucial part of almost all stages of plant life, from embryo patterning to apical meristem regulation, organ development and eventually senescence. The cytokinin signalling pathway involves the co-ordination of three types of proteins: histidine kinase receptors to perceive the signal, histidine phosphotransfer proteins to relay the signal, and response regulators to provide signal output. This pathway contains both positive and negative elements that function in a complex co-ordinated manner to control cytokinin-regulated plant responses. Although much is known about how this cytokinin signal is perceived and initially regulated, there are still many avenues that need to be explored before the role of cytokinin in the control of plant processes is fully understood. © 2015 Authors; published by Portland Press Limited.

  20. Signaling aggression.

    Science.gov (United States)

    van Staaden, Moira J; Searcy, William A; Hanlon, Roger T

    2011-01-01

    From psychological and sociological standpoints, aggression is regarded as intentional behavior aimed at inflicting pain and manifested by hostility and attacking behaviors. In contrast, biologists define aggression as behavior associated with attack or escalation toward attack, omitting any stipulation about intentions and goals. Certain animal signals are strongly associated with escalation toward attack and have the same function as physical attack in intimidating opponents and winning contests, and ethologists therefore consider them an integral part of aggressive behavior. Aggressive signals have been molded by evolution to make them ever more effective in mediating interactions between the contestants. Early theoretical analyses of aggressive signaling suggested that signals could never be honest about fighting ability or aggressive intentions because weak individuals would exaggerate such signals whenever they were effective in influencing the behavior of opponents. More recent game theory models, however, demonstrate that given the right costs and constraints, aggressive signals are both reliable about strength and intentions and effective in influencing contest outcomes. Here, we review the role of signaling in lieu of physical violence, considering threat displays from an ethological perspective as an adaptive outcome of evolutionary selection pressures. Fighting prowess is conveyed by performance signals whose production is constrained by physical ability and thus limited to just some individuals, whereas aggressive intent is encoded in strategic signals that all signalers are able to produce. We illustrate recent advances in the study of aggressive signaling with case studies of charismatic taxa that employ a range of sensory modalities, viz. visual and chemical signaling in cephalopod behavior, and indicators of aggressive intent in the territorial calls of songbirds. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. octene derivatives

    Indian Academy of Sciences (India)

    Ultrasonication; trimethylsilyloxy-derivatives; bicyclo[2.2.2]octene; Diels–Alder reaction; crystal structure; C–H. . . O and π...π interactions. 1. ... of silyl- derivatives were studied.8 The structural studies indicated a self-assembly ..... Technology (DST), New Delhi, India for the financial assistance. References. 1. Zhao F, Zhang ...

  2. Financial Derivatives

    DEFF Research Database (Denmark)

    Wigan, Duncan

    2013-01-01

    Contemporary derivatives mark the development of capital and constitute a novel form of ownership. By reconfiguring the temporal, spatial and legal character of ownership derivatives present a substantive challenge to the tax collecting state. While fiscal systems are nationally bounded and inheren...

  3. Biologically-based signal processing system applied to noise removal for signal extraction

    Science.gov (United States)

    Fu, Chi Yung; Petrich, Loren I.

    2004-07-13

    The method and system described herein use a biologically-based signal processing system for noise removal for signal extraction. A wavelet transform may be used in conjunction with a neural network to imitate a biological system. The neural network may be trained using ideal data derived from physical principles or noiseless signals to determine to remove noise from the signal.

  4. Systemic signaling during plant defense.

    Science.gov (United States)

    Kachroo, Aardra; Robin, Guillaume P

    2013-08-01

    Systemic acquired resistance (SAR) is a type of pathogen-induced broad-spectrum resistance in plants. During SAR, primary infection-induced rapid generation and transportation of mobile signal(s) 'prepare' the rest of the plant for subsequent infections. Several, seemingly unrelated, mobile chemical inducers of SAR have been identified, at least two of which function in a feed-back regulatory loop with a lipid transfer-like protein. Signal(s) perception in the systemic tissues relies on the presence of an intact cuticle, the waxy layer covering all aerial parts of the plant. SAR results in chromatin modifications, which prime systemic tissues for enhanced and rapid signaling derived from salicylic acid, which along with its signaling components is key for SAR induction. This review summarizes recent findings related to SAR signal generation, movement, and perception. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Global Derivatives

    DEFF Research Database (Denmark)

    Andersen, Torben Juul

    approaches to dealing in the global business environment." - Sharon Brown-Hruska, Commissioner, Commodity Futures Trading Commission, USA. "This comprehensive survey of modern risk management using derivative securities is a fine demonstration of the practical relevance of modern derivatives theory to risk......""In Global Derivatives: A Strategic Risk Management Perspective", Torben Juul Andersen has succeeded to gather in one book a complete and thorough summary and an easy-to-read explanation of all types of derivative instruments and their background, and their use in modern management of risk......." - Steen Parsholt, Chairman and CEO, Aon Nordic Region. "Andersen has done a wonderful job of developing a comprehensive text that deals with risk management in global markets. I would recommend this book to any student or businessman who has a need to better understand the risks and risk management...

  6. Derivative chameleons

    Energy Technology Data Exchange (ETDEWEB)

    Noller, Johannes, E-mail: johannes.noller08@imperial.ac.uk [Theoretical Physics, Blackett Laboratory, Imperial College London, Prince Consort Road, London, SW7 2BZ (United Kingdom)

    2012-07-01

    We consider generalized chameleon models where the conformal coupling between matter and gravitational geometries is not only a function of the chameleon field φ, but also of its derivatives via higher order co-ordinate invariants (such as ∂{sub μ}φ∂{sup μ}φ,□φ,...). Specifically we consider the first such non-trivial conformal factor A(φ,∂{sub μ}φ∂{sup μ}φ). The associated phenomenology is investigated and we show that such theories have a new generic mass-altering mechanism, potentially assisting the generation of a sufficiently large chameleon mass in dense environments. The most general effective potential is derived for such derivative chameleon setups and explicit examples are given. Interestingly this points us to the existence of a purely derivative chameleon protected by a shift symmetry for φ → φ+c. We also discuss potential ghost-like instabilities associated with mass-lifting mechanisms and find another, mass-lowering and instability-free, branch of solutions. This suggests that, barring fine-tuning, stable derivative models are in fact typically anti-chameleons that suppress the field's mass in dense environments. Furthermore we investigate modifications to the thin-shell regime and prove a no-go theorem for chameleon effects in non-conformal geometries of the disformal type.

  7. Electricity derivatives

    CERN Document Server

    Aïd, René

    2015-01-01

    Offering a concise but complete survey of the common features of the microstructure of electricity markets, this book describes the state of the art in the different proposed electricity price models for pricing derivatives and in the numerical methods used to price and hedge the most prominent derivatives in electricity markets, namely power plants and swings. The mathematical content of the book has intentionally been made light in order to concentrate on the main subject matter, avoiding fastidious computations. Wherever possible, the models are illustrated by diagrams. The book should allow prospective researchers in the field of electricity derivatives to focus on the actual difficulties associated with the subject. It should also offer a brief but exhaustive overview of the latest techniques used by financial engineers in energy utilities and energy trading desks.

  8. Gibberellin signaling.

    Science.gov (United States)

    Hartweck, Lynn M

    2008-12-01

    This review covers recent advances in gibberellin (GA) signaling. GA signaling is now understood to hinge on DELLA proteins. DELLAs negatively regulate GA response by activating the promoters of several genes including Xerico, which upregulates the abscisic acid pathway which is antagonistic to GA. DELLAs also promote transcription of the GA receptor, GIBBERELLIN INSENSITIVE DWARF 1 (GID1) and indirectly regulate GA biosynthesis genes enhancing GA responsiveness and feedback control. A structural analysis of GID1 provides a model for understanding GA signaling. GA binds within a pocket of GID1, changes GID1 conformation and increases the affinity of GID1 for DELLA proteins. GA/GID1/DELLA has increased affinity for an F-Box protein and DELLAs are subsequently degraded via the proteasome. Therefore, GA induces growth through degradation of the DELLAs. The binding of DELLA proteins to three of the PHYTOCHROME INTERACTING FACTOR (PIF) proteins integrates light and GA signaling pathways. This binding prevents PIFs 3, 4, and 5 from functioning as positive transcriptional regulators of growth in the dark. Since PIFs are degraded in light, these PIFs can only function in the combined absence of light and presence of GA. New analyses suggest that GA signaling evolved at the same time or just after the plant vascular system and before plants acquired the capacity for seed reproduction. An analysis of sequences cloned from Physcomitrella suggests that GID1 and DELLAs were the first to evolve but did not initially interact. The more recently diverging spike moss Selaginella has all the genes required for GA biosynthesis and signaling, but the role of GA response in Selaginella physiology remains a mystery.

  9. Complex derivatives

    Science.gov (United States)

    Battiston, Stefano; Caldarelli, Guido; Georg, Co-Pierre; May, Robert; Stiglitz, Joseph

    2013-03-01

    The intrinsic complexity of the financial derivatives market has emerged as both an incentive to engage in it, and a key source of its inherent instability. Regulators now faced with the challenge of taming this beast may find inspiration in the budding science of complex systems.

  10. Subgraph detection using graph signals

    KAUST Repository

    Chepuri, Sundeep Prabhakar

    2017-03-06

    In this paper we develop statistical detection theory for graph signals. In particular, given two graphs, namely, a background graph that represents an usual activity and an alternative graph that represents some unusual activity, we are interested in answering the following question: To which of the two graphs does the observed graph signal fit the best? To begin with, we assume both the graphs are known, and derive an optimal Neyman-Pearson detector. Next, we derive a suboptimal detector for the case when the alternative graph is not known. The developed theory is illustrated with numerical experiments.

  11. Effects of oxatomide and derivatives on high affinity IgE receptor-activated signal transduction pathways in rat basophilic leukemia cells : Role of protein tyrosine hyperphosphorylation and inhibition of extracellular calcium influx

    NARCIS (Netherlands)

    Paulussen, JJC; Fischer, MJE; Roozendaal, RL; van der Heijden, VC; van Dijken, P.; de Mol, NJ; Janssen, LHM

    1998-01-01

    The antiallergic drug oxatomide and analogs inhibit mediator release from a rat basophilic leukemia (RBL-2H3) cell line, which is frequently used as a mast cell model. By investigating a series of derivatives of oxatomide with different inhibiting activities on exocytosis, we aimed to evaluate the

  12. CD49f and CD61 identify Her2/neu-induced mammary tumor-initiating cells that are potentially derived from luminal progenitors and maintained by the integrin-TGFβ signaling.

    Science.gov (United States)

    Lo, P-K; Kanojia, D; Liu, X; Singh, U P; Berger, F G; Wang, Q; Chen, H

    2012-05-24

    Human epidermal growth factor receptor 2 (HER2)/Neu is overexpressed in 20-30% of breast cancers and associated with aggressive phenotypes and poor prognosis. For deciphering the role of HER2/Neu in breast cancer, mouse mammary tumor virus (MMTV)-Her2/neu transgenic mice that develop mammary tumors resembling human HER2-subtype breast cancer have been established. Several recent studies have revealed that HER2/Neu is overexpressed in and regulates self renewal of breast tumor-initiating cells (TICs). However, in the MMTV-Her2/neu transgenic mouse model, the identity of TICs remains elusive, despite previous studies showing supportive evidence for existence of TICs in Her2/neu-induced mammary tumors. Through systematic screening and characterization, we identified that surface markers CD49f, CD61 and ESA were aberrantly overexpressed in Her2-overexpressing mammary tumor cells. Analysis of these markers and CD24 detected anomalous expansion of the luminal progenitor population in preneoplastic mammary glands of Her2/neu transgenic mice, indicating that aberrant luminal progenitors originated in Her2-induced mammary tumors. The combined markers, CD49f and CD61, further delineated the CD49f(high)CD61(high)-sorted fraction as a TIC-enriched population, which displayed increased tumorsphere formation ability, enhanced tumorigenicity both in vitro and in vivo and drug resistance to pacitaxel and doxorubicin. Moreover, the TIC-enriched population manifested increased transforming growth factor-β (TGFβ) signaling and exhibited gene expression signatures of stemness, TGFβ signaling and epithelial-to-mesenchymal transition. Our findings that self-renewal and clonogenicity of TICs were suppressed by pharmacologically inhibiting the TGFβ signaling further indicate that the TGFβ pathway is vital for maintenance of the TIC population. Finally, we showed that the integrin-β3 (CD61) signaling pathway was required for sustaining active TGFβ signaling and self-renewal of TICs

  13. On Generalized Fractional Differentiator Signals

    Directory of Open Access Journals (Sweden)

    Hamid A. Jalab

    2013-01-01

    Full Text Available By employing the generalized fractional differential operator, we introduce a system of fractional order derivative for a uniformly sampled polynomial signal. The calculation of the bring in signal depends on the additive combination of the weighted bring-in of N cascaded digital differentiators. The weights are imposed in a closed formula containing the Stirling numbers of the first kind. The approach taken in this work is to consider that signal function in terms of Newton series. The convergence of the system to a fractional time differentiator is discussed.

  14. Discovery of 1-(3-aryl-4-chlorophenyl)-3-(p-aryl)urea derivatives against breast cancer by inhibiting PI3K/Akt/mTOR and Hedgehog signalings.

    Science.gov (United States)

    Li, Wenlu; Sun, Qinsheng; Song, Lu; Gao, Chunmei; Liu, Feng; Chen, Yuzong; Jiang, Yuyang

    2017-12-01

    PI3K/Akt/mTOR and hedgehog (Hh) signalings are two important pathways in breast cancer, which are usually connected with the drug resistance and cancer migration. Many studies indicated that PI3K/Akt/mTOR inhibitors and Hh inhibitors displayed synergistic effects, and the combination of the two signaling drugs could delay drug resistance and inhibit cancer migration in breast cancer. Therefore, the development of molecules simultaneously inhibiting these two pathways is urgent needed. Based on the structures of PI3K inhibitor buparlisib and Hh inhibitor vismodegib, a series of hybrid structures were designed and synthesized utilizing rational drug design and computer-based drug design. Several compounds displayed excellent antiproliferative activities against several breast cancer cell lines, including triple-negative breast cancer (TNBC) MDA-MB-231 cell. Further mechanistic studies demonstrated that the representative compound 9i could inhibit both PI3K/Akt/mTOR and hedgehog (Hh) signalings by inhibiting the phosphorylation of S6K and Akt as well as decreasing the SAG elevated expression of Gli1. Compound 9i could also induce apoptosis remarkably in T47D and MDA-MB-231 cells. In the transwell assay, 9i showed significant inhibition on the migration of MDA-MB-231. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  15. Aeroelastic analysis for helicopter rotor blades with time-variable, non-linear structural twist and multiple structural redundancy: Mathematical derivation and program user's manual

    Science.gov (United States)

    Bielawa, R. L.

    1976-01-01

    The differential equations of motion for the lateral and torsional deformations of a nonlinearly twisted rotor blade in steady flight conditions together with those additional aeroelastic features germane to composite bearingless rotors are derived. The differential equations are formulated in terms of uncoupled (zero pitch and twist) vibratory modes with exact coupling effects due to finite, time variable blade pitch and, to second order, twist. Also presented are derivations of the fully coupled inertia and aerodynamic load distributions, automatic pitch change coupling effects, structural redundancy characteristics of the composite bearingless rotor flexbeam - torque tube system in bending and torsion, and a description of the linearized equations appropriate for eigensolution analyses. Three appendixes are included presenting material appropriate to the digital computer program implementation of the analysis, program G400.

  16. Prosocial Signalling

    DEFF Research Database (Denmark)

    Kahsay, Goytom Abraha

    In contrast to the standard economic theory predictions, it seems clear that people do spend their time and resource to benefit others. Many lab and field experiment studies show that people display prosocial preferences such as altruism, reciprocity and conditional cooperation, fairness, etc...... signalling can cause reverse price reactions resembling the crowding-out of pre-existing motives for prosocial behavior seen in situations of volunteering and charitable giving. Using a unique combination of questionnaire and purchase panel data, it presents evidence of such reputation-driven reverse price...

  17. Spectral Correlation of Multicarrier Modulated Signals and Its Application for Signal Detection

    Directory of Open Access Journals (Sweden)

    Zhang Haijian

    2010-01-01

    Full Text Available Spectral correlation theory for cyclostationary time-series signals has been studied for decades. Explicit formulas of spectral correlation function for various types of analog-modulated and digital-modulated signals are already derived. In this paper, we investigate and exploit the cyclostationarity characteristics for two kinds of multicarrier modulated (MCM signals: conventional OFDM and filter bank based multicarrier (FBMC signals. The spectral correlation characterization of MCM signal can be described by a special linear periodic time-variant (LPTV system. Using this LPTV description, we have derived the explicit theoretical formulas of nonconjugate and conjugate cyclic autocorrelation function (CAF and spectral correlation function (SCF for OFDM and FBMC signals. According to theoretical spectral analysis, Cyclostationary Signatures (CS are artificially embedded into MCM signal and a low-complexity signature detector is, therefore, presented for detecting MCM signal. Theoretical analysis and simulation results demonstrate the efficiency and robustness of this CS detector compared to traditionary energy detector.

  18. NMR Analysis of Some Pentacycloundecanedione Derivatives

    African Journals Online (AJOL)

    NJD

    The complete NMR elucidation of four pentacycloundecanedione (PCUdione) derivatives is described. Major proton shifts occur when additions are performed on the carbonyl carbons. Some of the carbon signals are also transposed. Despite the fact that the signals of the methine protons on the cage skeleton experience ...

  19. Hyaluronan carried by tumor-derived microvesicles induces IL-10 production in classical (CD14++CD16-) monocytes via PI3K/Akt/mTOR-dependent signalling pathway.

    Science.gov (United States)

    Lenart, Marzena; Rutkowska-Zapala, Magdalena; Baj-Krzyworzeka, Monika; Szatanek, Rafał; Węglarczyk, Kazimierz; Smallie, Timothy; Ziegler-Heitbrock, Löms; Zembala, Marek; Siedlar, Maciej

    2017-01-01

    Tumor-derived microvesicles (TMV) can mimic effects of tumor cells leading to an increased anti-inflammatory cytokine production, such as interleukin 10 (IL-10), by tumor-infiltrating monocytes and macrophages. Yet, the mechanism of IL-10 induction by TMV in monocytes remains unclear. The co-incubation of TMV derived from the human pancreas carcinoma cell line (HPC-4) with human monocytes resulted in a nearly 30-fold increase in IL-10 protein production. This effect operates at the level of transcription since monocytes transduced with an adenovirus containing IL-10-promoter luciferase reporter gene showed a 5-fold induction of luciferase activity after treatment with TMV. Since tumor cells can express hyaluronan (HA), which participates in tumor invasion and metastases, we have tested its effect on IL-10 expression. We showed that HA at the concentration of 100μg/ml induces IL-10 protein expression and the IL-10 promoter activation in monocytes. Moreover, hyaluronidase treatment of TMV reduced IL-10 protein production by 50% and promoter activity by 40%. Inhibitors of the PI3K/Akt/mTOR pathway reduced both, TMV-induced IL-10 promoter activity and protein production, and the same was observed in monocytes when stimulated by HPC-4 cells or HA. Inhibition of PI3K activity down-regulated phosphorylation of the Akt and (to a lesser extent) mTOR proteins in monocytes following TMV or HA stimulation. When comparing monocyte subsets, TMV induced IL-10 protein and mRNA synthesis only in classical CD14++CD16- but not in CD16-positive monocytes. Our data show that TMV induce IL-10 synthesis in human classical monocytes via HA, which, in turn, activates the PI3K/Akt/mTOR pathway. Copyright © 2015 Elsevier GmbH. All rights reserved.

  20. Fractional Derivative as Fractional Power of Derivative

    OpenAIRE

    Tarasov, Vasily E.

    2007-01-01

    Definitions of fractional derivatives as fractional powers of derivative operators are suggested. The Taylor series and Fourier series are used to define fractional power of self-adjoint derivative operator. The Fourier integrals and Weyl quantization procedure are applied to derive the definition of fractional derivative operator. Fractional generalization of concept of stability is considered.

  1. Volume control device for digital signals

    NARCIS (Netherlands)

    Schinkel, Daniel; van Tuijl, Adrianus Johannes Maria; Nuijten, Petrus A.C.M.

    2004-01-01

    A digital volume control device comprises a logic unit for volume control of digital input signals. Successively supplied m-bits words with maximally k bits active, derived from the output signals of or supplied by a volume control (4) with a quantizer (5) element the filtered m-bits workds are

  2. Rescue of an In Vitro Neuron Phenotype Identified in Niemann-Pick Disease, Type C1 Induced Pluripotent Stem Cell-Derived Neurons by Modulating the WNT Pathway and Calcium Signaling

    Science.gov (United States)

    Efthymiou, Anastasia G.; Steiner, Joe; Pavan, William J.; Wincovitch, Stephen; Larson, Denise M.; Porter, Forbes D.; Rao, Mahendra S.

    2015-01-01

    Niemann-Pick disease, type C1 (NPC1) is a familial disorder that has devastating consequences on postnatal development with multisystem effects, including neurodegeneration. There is no Food and Drug Administration-approved treatment option for NPC1; however, several potentially therapeutic compounds have been identified in assays using yeast, rodent models, and NPC1 human fibroblasts. Although these discoveries were made in fibroblasts from NPC1 subjects and were in some instances validated in animal models of the disease, testing these drugs on a cell type more relevant for NPC1 neurological disease would greatly facilitate both study of the disease and identification of more relevant therapeutic compounds. Toward this goal, we have generated an induced pluripotent stem cell line from a subject homozygous for the most frequent NPC1 mutation (p.I1061T) and subsequently created a stable line of neural stem cells (NSCs). These NSCs were then used to create neurons as an appropriate disease model. NPC1 neurons display a premature cell death phenotype, and gene expression analysis of these cells suggests dysfunction of important signaling pathways, including calcium and WNT. The clear readout from these cells makes them ideal candidates for high-throughput screening and will be a valuable tool to better understand the development of NPC1 in neural cells, as well as to develop better therapeutic options for NPC1. PMID:25637190

  3. Suppression of Very Early Stage Of Adipogenesis by Baicalein, a Plant-Derived Flavonoid through Reduced Akt-C/EBPα-GLUT4 Signaling-Mediated Glucose Uptake in 3T3-L1 Adipocytes.

    Directory of Open Access Journals (Sweden)

    Yukari Nakao

    Full Text Available Baicalein has been used as a Chinese medicine, and is an abundant plant flavonoid present in fruits and vegetables. Here, we examined the effects of baicalein in adipogenesis and investigated its molecular mechanism in adipocytes. Baicalein lowered the intracellular lipid accumulation and decreased the transcription levels of the adipocyte-specific genes in mouse 3T3-L1 adipocytes. Glucose uptake mediated by glucose transporter 4 (GLUT4 was reduced, causing down-regulation of the intracellular lipid accumulation. These reductions were also observed even when baicalein was added in only early stage of adipogenesis (0-2 days of 6-day-adipogenesis. Chromatin immunoprecipitation assay showed that baicalein decreased the binding level of C/EBPα protein to the promoter region of the GLUT4 gene. Phosphorylation of Akt at 1 h after the initiation of adipogenesis was inhibited by the treatment with baicalein. Inhibition during only the first 1.5 h after the initiation of adipogenesis by baicalein or an Akt inhibitor was enough to decrease the lipid contents in the cells undergoing adipocyte differentiation for 6 days. These results indicate that baicalein decreased the intracellular lipid accumulation by down-regulation of glucose uptake via repression of Akt-C/EBPα-GLUT4 signaling in the very early stage of adipogenesis of 3T3-L1 adipocytes.

  4. Exosomes from Human-Induced Pluripotent Stem Cell–Derived Mesenchymal Stromal Cells (hiPSC-MSCs Protect Liver against Hepatic Ischemia/ Reperfusion Injury via Activating Sphingosine Kinase and Sphingosine-1-Phosphate Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Yingdong Du

    2017-09-01

    Full Text Available Background/Aims: This study aimed to evaluate the effects of exosomes produced by human-induced pluripotent stem cell-derived mesenchymal stromal cells (hiPSC-MSCs-Exo on hepatic ischemia-reperfusion (I/R injury, as well as the underlying mechanisms. Methods: Exosomes derived from hiPSC-MSCs were isolated and characterized both biochemically and biophysically. hiPSC-MSCs-Exo were injected systemically into a murine ischemia/reperfusion injury model via the inferior vena cava, and then the therapeutic effects were evaluated. The serum levels of transaminases (aspartate aminotransferase (AST and alanine aminotransferase (ALT, as well as histological changes were examined. Primary hepatocytes and human hepatocyte cell line HL7702 were used to test whether exosomes could induce hepatocytes proliferation in vitro. In addition, the expression levels of proliferation markers (proliferation cell nuclear antigen, PCNA; Phosphohistone-H3, PHH3 were measured by immunohistochemistry and Western blot. Moreover, SK inhibitor (SKI-II and S1P1 receptor antagonist (VPC23019 were used to investigate the role of sphingosine kinase and sphingosine-1-phosphate-dependent pathway in the effects of hiPSC-MSCs-Exo on hepatocytes. Results: hiPSCs were efficiently induced into hiPSC-MSCs that had typical MSC characteristics. hiPSC-MSCs-Exo had diameters ranging from 100 to 200 nm and expressed exosome markers (Alix, CD63 and CD81. After hiPSC-MSCs-Exo administration, hepatocyte necrosis and sinusoidal congestion were markedly suppressed in the ischemia/reperfusion injury model, with lower histopathological scores. The levels of hepatocyte injury markers AST and ALT were significantly lower in the treatment group compared to control, and the expression levels of proliferation markers (PCNA and PHH3 were greatly induced after hiPSC-MSCs-Exo administration. Moreover, hiPSC-MSCs-Exo also induced primary hepatocytes and HL7702 cells proliferation in vitro in a dose

  5. Qualitative and quantitative re-evaluation of epidermal growth factor-ErbB1 action on developing midbrain dopaminergic neurons in vivo and in vitro: target-derived neurotrophic signaling (Part 1).

    Science.gov (United States)

    Iwakura, Yuriko; Zheng, Yingjun; Sibilia, Maria; Abe, Yuichi; Piao, Ying-Shan; Yokomaku, Daisaku; Wang, Ran; Ishizuka, Yuta; Takei, Nobuyuki; Nawa, Hiroyuki

    2011-07-01

    Although epidermal growth factor (EGF) receptor (ErbB1) is implicated in Parkinson's disease and schizophrenia, the neurotrophic action of ErbB1 ligands on nigral dopaminergic neurons remains controversial. Here, we ascertained colocalization of ErbB1 and tyrosine hydroxylase (TH) immunoreactivity and then characterized the neurotrophic effects of ErbB1 ligands on this cell population. In mesencephalic culture, EGF and glial-derived neurotrophic factor (GDNF) similarly promoted survival and neurite elongation of dopaminergic neurons and dopamine uptake. The EGF-promoted dopamine uptake was not inhibited by GDNF-neutralizing antibody or TrkB-Fc, whereas EGF-neutralizing antibody fully blocked the neurotrophic activity of the conditioned medium that was prepared from EGF-stimulated mesencephalic cultures. The neurotrophic action of EGF was abolished by ErbB1 inhibitors and genetic disruption of erbB1 in culture. In vivo administration of ErbB1 inhibitors to rat neonates diminished TH and dopamine transporter (DAT) levels in the striatum and globus pallidus but not in the frontal cortex. In parallel, there was a reduction in the density of dopaminergic varicosities exhibiting intense TH immunoreactivity. In agreement, postnatal erbB1-deficient mice exhibited similar decreases in TH levels. Although neurotrophic supports to dopaminergic neurons are redundant, these results confirm that ErbB1 ligands contribute to the phenotypic and functional development of nigral dopaminergic neurons. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

  6. Protective effect of chronic caffeine intake on gene expression of brain derived neurotrophic factor signaling and the immunoreactivity of glial fibrillary acidic protein and Ki-67 in Alzheimer's disease.

    Science.gov (United States)

    Ghoneim, Fatma M; Khalaf, Hanaa A; Elsamanoudy, Ayman Z; Abo El-Khair, Salwa M; Helaly, Ahmed M N; Mahmoud, El-Hassanin M; Elshafey, Saad H

    2015-01-01

    Alzheimer's disease (AD) is a neurodegenerative disorder with progressive degeneration of the hippocampal and cortical neurons. This study was designed to demonstrate the protective effect of caffeine on gene expression of brain derived neurotrophic factor (BDNF) and its receptor neural receptor protein-tyrosine kinase-β (TrkB) as well as glial fibrillary acidic protein (GFAP) and Ki-67 immunoreactivity in Aluminum chloride (AlCl3) induced animal model of AD. Fifty adult rats included in this study were classified into 5 group (10 rats each); negative and positive control groups (I&II), AD model group (III), group treated with caffeine from the start of AD induction (IV) and group treated with caffeine two weeks before AD induction (V). Hippocampal tissue BDNF and its receptor (TrkB) gene expression by real time RT-PCR in addition to immunohistochemical study of GFAP and Ki67 immunoreactivity were performed for all rats in the study. The results of this study revealed that caffeine has protective effect through improving the histological and immunohistochemical findings induced by AlCl3 as well as BDNF and its receptor gene expression. It could be concluded from the current study, that chronic caffeine consumption in a dose of 1.5 mg/kg body weight daily has a potentially good protective effect against AD.

  7. A new 2α,5α,10β,14β-tetraacetoxy-4(20,11-taxadiene (SIA derivative overcomes paclitaxel resistance by inhibiting MAPK signaling and increasing paclitaxel accumulation in breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Mei Mei

    Full Text Available Tumor resistance due to multiple mechanisms seriously hinders the efficacy of chemotherapy drugs such as paclitaxel. The most widely studied P-glycoprotein inhibitors still have limited ability to reverse resistance in the clinic. In this study, NPB304, a novel Sinenxan A (SIA derivative, was found to significantly sensitize resistant breast cancer cells to paclitaxel in vitro and in vivo. Treatment with NPB304 increased paclitaxel-induced apoptosis in a p53-dependent manner through PARP cleavage. Importantly, NPB304 enhanced the antitumor effect of paclitaxel in resistant breast tumor xenografts in nude mice without significantly affecting weight loss. NPB304 regulated cell resistance through inhibition of MAPK pathway components, including p-ERK and p-p38. Moreover, NPB304 increased paclitaxel accumulation by affecting P-gp function. In addition to increasing Rhodamine 123 accumulation, NPB304 promoted bidirectional permeability but decreased the efflux ratio of paclitaxel in a Caco-2 monolayer model, thereby increasing the intracellular concentration of paclitaxel. Similarly, NPB304 increased the concentration of paclitaxel in the resistant tumor tissue. Hence, NPB304 is a novel compound that promotes the sensitization of resistant cells to paclitaxel through multiple mechanisms and has the potential for use in combination therapies to treat resistant breast cancer.

  8. Derivation of GFDM Based on OFDM Principles

    Energy Technology Data Exchange (ETDEWEB)

    Hussein Moradi; Behrouz Farhang-Boroujeny

    2015-06-01

    This paper starts with discussing the principle based on which the celebrated orthogonal frequency division multiplexing (OFDM) signals are constructed. It then extends the same principle to construct the newly introduced generalized frequency division multiplexing (GFDM) signals. This novel derivation sheds light on some interesting properties of GFDM. In particular, our derivation seamlessly leads to an implementation of GFDM transmitter which has significantly lower complexity than what has been reported so far. Our derivation also facilitates a trivial understanding of how GFDM (similar to OFDM) can be applied in MIMO channels.

  9. On $n$-derivations

    Directory of Open Access Journals (Sweden)

    Mohammad Hossein Sattari

    2016-06-01

    Full Text Available In this article, the notion of $n-$derivation is introduced for all integers $ngeq 2$. Although all derivations are $n-$derivations,  in general these notions are not equivalent. Some properties of ordinary derivations are  investigated for $n-$derivations. Also, we show that under certain mild condition  $n-$derivations are derivations.

  10. Analytical application of derivative spectrophotometry

    Directory of Open Access Journals (Sweden)

    VIOLETA M. STEFANOVIC

    2000-07-01

    Full Text Available 1. Introduction 2. Basic characteristics of derivative spectrophotometry 2.1. Increase of spectra resolution 2.2. Elimination of the influence of baseline shift and matrix interferences 2.3. Enhancement of the detectability of minor spectral features 2.4. Precise determination of the positions of absorption maxima 2.5. Signal-to-noise ratio (SNR 2.6. Quantitative analysis 3. Analytical applications 3.1. Inorganic analysis 3.2. Organic and pharmaceutical analysis 3.3. Analysis of food and water 3.4. Application of derivative spectrophotometry for the determination of equilibrium constants

  11. Resistin-induced stromal cell-derived factor-1 expression through Toll-like receptor 4 and activation of p38 MAPK/ NFκB signaling pathway in gastric cancer cells.

    Science.gov (United States)

    Hsieh, Yung-Yu; Shen, Chien-Heng; Huang, Wen-Shih; Chin, Chih-Chien; Kuo, Yi-Hung; Hsieh, Meng Chiao; Yu, Hong-Ren; Chang, Te-Sheng; Lin, Tseng-Hsi; Chiu, Yung-Wei; Chen, Cheng-Nan; Kuo, Hsing-Chun; Tung, Shui-Yi

    2014-06-14

    Stromal cell-derived factor-1 (SDF-1) (CXC chemokine ligand-12)/CXC chemokine receptor 4 (CXCR4) is involved in the carcinogenesis of human gastric cancer, where it stimulates angiogenesis and favors metastasis of tumor cells to distant organs. In addition, resistin is suggested to be an important link between obesity and the development of gastric cancer. Resistin has identified as an important player in inflammatory responses, and emerged as a mediator in inflammation-associated cancer. A limited number of studies have investigated the association of resistin and SDF-1 with gastric cancer. Herein, we investigated the molecular mechanisms by which resistin influences the expression of SDF-1 in gastric carcinoma cells. Human gastric cancer cell lines were exposed to doses of resistin; SDF-1 expression and secretion levels were then determined. Real-time polymerase chain reaction and western blotting analyses were performed to clarify molecular changes. Inhibition of Toll-like receptor 4 (TLR4) by a competitive antagonist inhibited resistin-induced SDF-1 expression. Pharmacological inhibitors and small interfering RNA (siRNA) demonstrated that activation of the p38 mitogen-activated protein kinase (MAPK) pathway is critical for resistin-induced SDF-1 expression mediated by TLR4. The promoter activity and transcription factor enzyme-linked immunosorbent assay revealed that resistin induced expression of SDF-1 mediated by NF-κB in gastric cancer cells. Inhibition of p38 MARK activation blocked the SDF-1-induced expression and the SDF-1 promoter activity in the cancer gastric cells. Chromatin immunoprecipitation assay revealed that inhibition of p38 MARK activation also blocked the resistin-increased NF-κB-DNA-binding activity. Resistin-induced SDF-1 upregulation by activation of TLR4, p38 MARK and NF-κB may explain a new role of resistin in the link of obesity and gastric cancer.

  12. Cell-free carrier system for localized delivery of peripheral blood cell-derived engineered factor signaling: towards development of a one-step device for autologous angiogenic therapy.

    Science.gov (United States)

    Hadjipanayi, E; Bauer, A T; Moog, P; Salgin, B; Kuekrek, H; Fersch, B; Hopfner, U; Meissner, T; Schlüter, A; Ninkovic, M; Machens, H G; Schilling, A F

    2013-07-10

    Spatiotemporally-controlled delivery of hypoxia-induced angiogenic factor mixtures has been identified by this group as a promising strategy for overcoming the limited ability of chronically ischemic tissues to generate adaptive angiogenesis. We previously developed an implantable, as well as an injectable system for delivering fibroblast-produced factors in vivo. Here, we identify peripheral blood cells (PBCs) as the ideal factor-providing candidates, due to their autologous nature, ease of harvest and ample supply, and investigate wound-simulating biochemical and biophysical environmental parameters that can be controlled to optimize PBC angiogenic activity. It was found that hypoxia (3% O₂) significantly affected the expression of a range of angiogenesis-related factors including VEGF, angiogenin and thrombospondin-1, relative to the normoxic baseline. While all three factors underwent down-regulation over time under hypoxia, there was significant variation in the temporal profile of their expression. VEGF expression was also found to be dependent on cell-scaffold material composition, with fibrin stimulating production the most, followed by collagen and polystyrene. Cell-scaffold matrix stiffness was an additional important factor, as shown by higher VEGF protein levels when PBCs were cultured on stiff vs. compliant collagen hydrogel scaffolds. Engineered PBC-derived factor mixtures could be harvested within cell-free gel and microsphere carriers. The angiogenic effectiveness of factor-loaded carriers could be demonstrated by the ability of their releasates to induce endothelial cell tubule formation and directional migration in in vitro Matrigel assays, and microvessel sprouting in the aortic ring assay. To aid the clinical translation of this approach, we propose a device design that integrates this system, and enables one-step harvesting and delivering of angiogenic factor protein mixtures from autologous peripheral blood. This will facilitate the

  13. Analytical application of derivative spectrophotometry

    OpenAIRE

    VIOLETA M. STEFANOVIC; GORDANA V. POPOVIC; LIDIJA B. PFENDT

    2000-01-01

    1. Introduction 2. Basic characteristics of derivative spectrophotometry 2.1. Increase of spectra resolution 2.2. Elimination of the influence of baseline shift and matrix interferences 2.3. Enhancement of the detectability of minor spectral features 2.4. Precise determination of the positions of absorption maxima 2.5. Signal-to-noise ratio (SNR) 2.6. Quantitative analysis 3. Analytical applications 3.1. Inorganic analysis 3.2. Organic and pharmaceutical analysis 3.3. An...

  14. Theory of net analyte signal vectors in inverse regression

    DEFF Research Database (Denmark)

    Bro, R.; Andersen, Charlotte Møller

    2003-01-01

    The. net analyte signal and the net analyte signal vector are useful measures in building and optimizing multivariate calibration models. In this paper a theory for their use in inverse regression is developed. The theory of net analyte signal was originally derived from classical least squares...

  15. Signal-to-noise ratio determination circuit

    Science.gov (United States)

    Deerkoski, L. F. (Inventor)

    1973-01-01

    A signal-to-noise ratio (SNR) determination of an input is described, having signal components within a given frequency range and noise components, without actual measurement of the noise components. Bandpass limiter having a constant signal plus noise output level is connected to the output of the first filter, the signal-to-noise ratio of the input to the bandpass limiter being linearly related to the dbm level of signal components at the output. Calibration is connected to the bandpass limiter and is responsive to the signal components at the output to derive the SNR of the input to the determination circuit. The SNR determination circuit is disclosed for use in a diversity receiver having a plurality of input channels.

  16. Continuous-time signals

    CERN Document Server

    Shmaliy, Yuriy

    2006-01-01

    Gives a modern description of continuous-time deterministic signals Signal formation techniquesTime vs. frequency and frequency vs. time analysisCorrelation and energy analysisNarrowband signals and sampling.

  17. Basic digital signal processing

    CERN Document Server

    Lockhart, Gordon B

    1985-01-01

    Basic Digital Signal Processing describes the principles of digital signal processing and experiments with BASIC programs involving the fast Fourier theorem (FFT). The book reviews the fundamentals of the BASIC program, continuous and discrete time signals including analog signals, Fourier analysis, discrete Fourier transform, signal energy, power. The text also explains digital signal processing involving digital filters, linear time-variant systems, discrete time unit impulse, discrete-time convolution, and the alternative structure for second order infinite impulse response (IIR) sections.

  18. Phospholipid, arachidonate and eicosanoid signaling in schizophrenia

    Directory of Open Access Journals (Sweden)

    Messamore Erik

    2016-01-01

    Full Text Available This paper reviews the potential role of arachidonic acid in the pathophysiology of schizophrenia. We discuss how abnormal levels of arachidonic acid may arise, and how dysregulation of signaling molecules derived from it have the potential to disrupt not only dopamine signaling, but numerous other physiological processes associated with the illness. Pharmacological doses of niacin stimulate the release of arachidonic acid; and arachidonic acid-derived molecules in turn dilate blood vessels in the skin. A blunted skin flush response to niacin is reliably observed among patients with schizophrenia. The niacin response abnormality may thus serve as a biomarker to identify a physiological subtype of schizophrenia associated with defective arachidonic acid-derived signaling.

  19. [Dynamic Pulse Signal Processing and Analyzing in Mobile System].

    Science.gov (United States)

    Chou, Yongxin; Zhang, Aihua; Ou, Jiqing; Qi, Yusheng

    2015-09-01

    In order to derive dynamic pulse rate variability (DPRV) signal from dynamic pulse signal in real time, a method for extracting DPRV signal was proposed and a portable mobile monitoring system was designed. The system consists of a front end for collecting and wireless sending pulse signal and a mobile terminal. The proposed method is employed to extract DPRV from dynamic pulse signal in mobile terminal, and the DPRV signal is analyzed both in the time domain and the frequency domain and also with non-linear method in real time. The results show that the proposed method can accurately derive DPRV signal in real time, the system can be used for processing and analyzing DPRV signal in real time.

  20. Measures of distance between speech signals in the frequency domain

    Science.gov (United States)

    Deseta, D.

    1984-02-01

    The energy density spectra and the time behavior of the autoregressive model of voice signals are studied. The first is a complete representation of the voice signal in the frequency domain, derived from the application of the Fourier transform to the sampled signal. The second is based on a voice signal generation model in which the channel is represented by poles only (resonances). A symmetrical version of the Itakura distance is the best compromise between conflicting requirements.

  1. Interkingdom signaling in plant-microbe interactions.

    Science.gov (United States)

    Kan, Jinhong; Fang, Rongxiang; Jia, Yantao

    2017-08-01

    The widespread communications between prokaryotes and eukaryotes via signaling molecules are believed to affect gene expression in both partners. During the communication process, the contacted organisms produce and release small molecules that establish communication channels between two kingdoms-this procedure is known as interkingdom signaling. Interkingdom communications are widespread between pathogenic or beneficial bacteria and their host plants, with diversified outcomes depending on the specific chemical-triggered signaling pathways. Deciphering the signals or language of this interkingdom communication and uncovering the underlying mechanisms are major current challenges in this field. It is evident that diverse signaling molecules can be produced or derived from bacteria and plants, and researchers have sought to identify these signals and explore the mechanisms of the signaling pathways. The results of such studies will lead to the development of strategies to improve plant disease resistance through controlling interkingdom signals, rather than directly killing the pathogenic bacteria. Also, the identification of signals produced by beneficial bacteria will be useful for agricultural applications. In this review, we summarize the recent progress of cross-kingdom interactions between plant and bacteria, and how LuxR-family transcription factors in plant associated bacterial quorum sensing system are involved in the interkingdom signaling.

  2. ROS signalling - specificity is required

    DEFF Research Database (Denmark)

    Møller, Ian M; Sweetlove, Lee J

    2010-01-01

    Reactive oxygen species (ROS) production increases in plants under stress. ROS can damage cellular components, but they can also act in signal transduction to help the cell counteract the oxidative damage in the stressed compartment. H2O2 might induce a general stress response, but it does not ha...... and regulate source-specific genes and in this way contribute to retrograde ROS signalling during oxidative stress. Likewise, unmodified peptides deriving from the breakdown of redundant proteins could help coordinate organellar and nuclear gene expression......Reactive oxygen species (ROS) production increases in plants under stress. ROS can damage cellular components, but they can also act in signal transduction to help the cell counteract the oxidative damage in the stressed compartment. H2O2 might induce a general stress response, but it does not have...... the required specificity to selectively regulate nuclear genes required for dealing with localized stress, e.g. in chloroplasts or mitochondria. Here we argue that peptides deriving from proteolytic breakdown of oxidatively damaged proteins have the requisite specificity to act as secondary ROS messengers...

  3. Digital signal processing laboratory

    CERN Document Server

    Kumar, B Preetham

    2011-01-01

    INTRODUCTION TO DIGITAL SIGNAL PROCESSING Brief Theory of DSP ConceptsProblem SolvingComputer Laboratory: Introduction to MATLAB®/SIMULINK®Hardware Laboratory: Working with Oscilloscopes, Spectrum Analyzers, Signal SourcesDigital Signal Processors (DSPs)ReferencesDISCRETE-TIME LTI SIGNALS AND SYSTEMS Brief Theory of Discrete-Time Signals and SystemsProblem SolvingComputer Laboratory: Simulation of Continuous Time and Discrete-Time Signals and Systems ReferencesTIME AND FREQUENCY ANALYSIS OF COMMUNICATION SIGNALS Brief Theory of Discrete-Time Fourier Transform (DTFT), Discrete Fourier Transform

  4. Signals, systems, transforms, and digital signal processing with Matlab

    CERN Document Server

    Corinthios, Michael

    2009-01-01

    Continuous-Time and Discrete-Time Signals and SystemsIntroductionContinuous-Time SignalsPeriodic FunctionsUnit Step FunctionGraphical Representation of FunctionsEven and Odd Parts of a FunctionDirac-Delta ImpulseBasic Properties of the Dirac-Delta ImpulseOther Important Properties of the ImpulseContinuous-Time SystemsCausality, StabilityExamples of Electrical Continuous-Time SystemsMechanical SystemsTransfer Function and Frequency ResponseConvolution and CorrelationA Right-Sided and a Left-Sided FunctionConvolution with an Impulse and Its DerivativesAdditional Convolution PropertiesCorrelation FunctionProperties of the Correlation FunctionGraphical InterpretationCorrelation of Periodic FunctionsAverage, Energy and Power of Continuous-Time SignalsDiscrete-Time SignalsPeriodicityDifference EquationsEven/Odd DecompositionAverage Value, Energy and Power SequencesCausality, StabilityProblemsAnswers to Selected ProblemsFourier Series ExpansionTrigonometric Fourier SeriesExponential Fourier SeriesExponential versus ...

  5. Interest rate derivatives

    DEFF Research Database (Denmark)

    Svenstrup, Mikkel

    This Ph.D. thesis consists of four self-contained essays on valuation of interest rate derivatives. In particular derivatives related to management of interest rate risk care are considered.......This Ph.D. thesis consists of four self-contained essays on valuation of interest rate derivatives. In particular derivatives related to management of interest rate risk care are considered....

  6. Endocannabinoid signaling in reward and addiction

    Science.gov (United States)

    Parsons, Loren H.; Hurd, Yasmin L.

    2015-01-01

    Brain endocannabinoid signaling influences the motivation for natural rewards (such as palatable food, sexual activity and social interaction) and modulates the rewarding effects of addictive drugs. Pathological forms of natural and drug-induced reward are associated with dysregulated endocannabinoid signaling that may derive from pre-existing genetic factors or from prolonged drug exposure. Impaired endocannabinoid signaling contributes to dysregulated synaptic plasticity, increased stress responsivity, negative emotional states, and craving that propel addiction. Understanding the contributions of endocannabinoid disruptions to behavioral and physiological traits provides insight into the endocannabinoid influence on addiction vulnerability. PMID:26373473

  7. Generalized Riemann derivative

    Directory of Open Access Journals (Sweden)

    Sorin Radulescu

    2013-03-01

    Full Text Available Initiated by Marshall Ash in 1966, the study of generalized Riemann derivative draw significant attention of the mathematical community and numerous studies where carried out since then. One of the major areas that benefits from these developments is the numerical analysis, as the use of generalized Riemann derivatives leads to solving a wider class of problems that are not solvable with the classical tools. This article studies the generalized Riemann derivative and its properties and establishes relationships between Riemann generalized derivative and the classical one. The existence of classical derivative implies the existence of the Riemann generalized derivative, and we study conditions necessary for the generalized Riemann derivative to imply the existence of the classical derivative. Furthermore, we provide conditions on the generalized Riemann derivative that are sufficient for the existence of the classical derivative.

  8. Synthetic Bioluminescent Coelenterazine Derivatives.

    Science.gov (United States)

    Nishihara, Ryo; Citterio, Daniel; Suzuki, Koji

    2016-01-01

    The development of coelenterazine (CTZ) derivatives resulting in superior optical characteristics is an efficient method to extend the range of its possible applications. Here, we describe the synthesis of three C-6 substituted CTZ derivatives retaining the recognition by Renilla luciferase (RLuc) and its derivatives. The novel derivatives are useful as bright blue-shifted CTZ derivatives, which can be used as an alternative to hitherto reported compound DeepBlueC™.

  9. Optimal Correlation Filters for Images with Signal-Dependent Noise

    Science.gov (United States)

    Downie, John D.; Walkup, John F.

    1994-01-01

    We address the design of optimal correlation filters for pattern detection and recognition in the presence of signal-dependent image noise sources. The particular examples considered are film-grain noise and speckle. Two basic approaches are investigated: (1) deriving the optimal matched filters for the signal-dependent noise models and comparing their performances with those derived for traditional signal-independent noise models and (2) first nonlinearly transforming the signal-dependent noise to signal-independent noise followed by the use of a classical filter matched to the transformed signal. We present both theoretical and computer simulation results that demonstrate the generally superior performance of the second approach in terms of the correlation peak signal-to-noise ratio.

  10. EUROmediCAT signal detection

    DEFF Research Database (Denmark)

    Given, Joanne E; Loane, Maria; Luteijn, Johannes Michiel

    2016-01-01

    and levonorgestrel/ethinylestradiol (OR 4.10, 95% CI 1.70-8.53; congenital heart disease/pulmonary valve stenosis and nucleoside/tide reverse transcriptase inhibitors (OR 5.01, 95% CI 1.99-14.20/OR 28.20, 95% CI 4.63-122.24); complete absence of a limb and pregnen (4) derivatives (OR 6.60, 95% CI 1......AIMS: To evaluate congenital anomaly (CA)-medication exposure associations produced by the new EUROmediCAT signal detection system and determine which require further investigation. METHODS: Data from 15 EUROCAT registries (1995-2011) with medication exposures at the chemical substance (5th level...

  11. EUROmediCAT signal detection

    DEFF Research Database (Denmark)

    Given, Joanne E; Loane, Maria; Luteijn, Johannes Michiel

    2016-01-01

    AIMS: To evaluate congenital anomaly (CA)-medication exposure associations produced by the new EUROmediCAT signal detection system and determine which require further investigation. METHODS: Data from 15 EUROCAT registries (1995-2011) with medication exposures at the chemical substance (5th level...... and levonorgestrel/ethinylestradiol (OR 4.10, 95% CI 1.70-8.53; congenital heart disease/pulmonary valve stenosis and nucleoside/tide reverse transcriptase inhibitors (OR 5.01, 95% CI 1.99-14.20/OR 28.20, 95% CI 4.63-122.24); complete absence of a limb and pregnen (4) derivatives (OR 6.60, 95% CI 1...

  12. Improving vehicle rear lighting and signalling.

    NARCIS (Netherlands)

    Roszbach, R.

    1972-01-01

    Measures that can be taken to improve vehicle rear-lighting and signaling are described in broad outline. These measures relate to the visibility of a vehicle, determination of its position (and derivates), the additional indication of specific vehicle-characteristics and preferable coding methods

  13. Integrating Retinoic Acid Signaling with Brain Function

    Science.gov (United States)

    Luo, Tuanlian; Wagner, Elisabeth; Drager, Ursula C.

    2009-01-01

    The vitamin A derivative retinoic acid (RA) regulates the transcription of about a 6th of the human genome. Compelling evidence indicates a role of RA in cognitive activities, but its integration with the molecular mechanisms of higher brain functions is not known. Here we describe the properties of RA signaling in the mouse, which point to…

  14. Overlay Spectrum Sharing using Improper Gaussian Signaling

    KAUST Repository

    Amin, Osama

    2016-11-30

    Improper Gaussian signaling (IGS) scheme has been recently shown to provide performance improvements in interference limited networks as opposed to the conventional proper Gaussian signaling (PGS) scheme. In this paper, we implement the IGS scheme in overlay cognitive radio system, where the secondary transmitter broadcasts a mixture of two different signals. The first signal is selected from the PGS scheme to match the primary message transmission. On the other hand, the second signal is chosen to be from the IGS scheme in order to reduce the interference effect on the primary receiver. We then optimally design the overlay cognitive radio to maximize the secondary link achievable rate while satisfying the primary network quality of service requirements. In particular, we consider full and partial channel knowledge scenarios and derive the feasibility conditions of operating the overlay cognitive radio systems. Moreover, we derive the superiority conditions of the IGS schemes over the PGS schemes supported with closed form expressions for the corresponding power distribution and the circularity coefficient and parameters. Simulation results are provided to support our theoretical derivations.

  15. Signal sciences workshop proceedings

    Energy Technology Data Exchange (ETDEWEB)

    Candy, J.V.

    1997-05-01

    This meeting is aimed primarily at signal processing and controls. The technical program for the 1997 Workshop includes a variety of efforts in the Signal Sciences with applications in the Microtechnology Area a new program at LLNL and a future area of application for both Signal/Image Sciences. Special sessions organized by various individuals in Seismic and Optical Signal Processing as well as Micro-Impulse Radar Processing highlight the program, while the speakers at the Signal Processing Applications session discuss various applications of signal processing/control to real world problems. For the more theoretical, a session on Signal Processing Algorithms was organized as well as for the more pragmatic, featuring a session on Real-Time Signal Processing.

  16. Retinoid signalling during embryogenesis

    NARCIS (Netherlands)

    Pijnappel, W.W.M.; Hendriks, H.F.J.; Durston, A.J.

    1996-01-01

    Conclusion: Retinoids are suspected to have multiple functions during embryogenesis, which are carried out via various different signal transduction pathways involving active retinoids and nuclear retinoid receptors. Research focuses on the identification of the retinoid signal transduction

  17. Ratiometric fluorescence signalling of fluoride ions by an ...

    Indian Academy of Sciences (India)

    ... Lecture Workshops · Refresher Courses · Symposia. Home; Journals; Journal of Chemical Sciences; Volume 119; Issue 2. Ratiometric fluorescence signalling of fluoride ions by an amidophthalimide derivative. Moloy Sarkar Raghavendra Yellampalli Bhaswati Bhattacharya Ravi Kumar Kanaparthi Anunay Samanta.

  18. Intraflagellar Transport (IFT) Role in Ciliary Assembly, Resorption and Signalling

    DEFF Research Database (Denmark)

    Pedersen, Lotte B; Rosenbaum, Joel L

    2008-01-01

    Cilia and flagella have attracted tremendous attention in recent years as research demonstrated crucial roles for these organelles in coordinating a number of physiologically and developmentally important signaling pathways, including the platelet-derived growth factor receptor (PDGFR) alpha, Sonic...

  19. Biomedical signal processing

    CERN Document Server

    Akay, Metin

    1994-01-01

    Sophisticated techniques for signal processing are now available to the biomedical specialist! Written in an easy-to-read, straightforward style, Biomedical Signal Processing presents techniques to eliminate background noise, enhance signal detection, and analyze computer data, making results easy to comprehend and apply. In addition to examining techniques for electrical signal analysis, filtering, and transforms, the author supplies an extensive appendix with several computer programs that demonstrate techniques presented in the text.

  20. Effects of Vocal Fold Nodules on Glottal Cycle Measurements Derived from High-Speed Videoendoscopy in Children

    OpenAIRE

    Patel, Rita R.; Harikrishnan Unnikrishnan; Donohue, Kevin D.

    2016-01-01

    The goal of this study is to quantify the effects of vocal fold nodules on vibratory motion in children using high-speed videoendoscopy. Differences in vibratory motion were evaluated in 20 children with vocal fold nodules (5-11 years) and 20 age and gender matched typically developing children (5-11 years) during sustained phonation at typical pitch and loudness. Normalized kinematic features of vocal fold displacements from the mid-membranous vocal fold point were extracted from the steady-...

  1. Intrarectal artemisinin derivatives

    NARCIS (Netherlands)

    Nosten, F.; van Vugt, M.; White, N. J.

    1998-01-01

    The artemisinin derivatives are the most potent antimalarials. They are rapidly absorbed orally, parenterally and intra-rectally. The latter mode of administration is particularly interesting in rural tropics. Preliminary studies have shown that artemisinin and its derivatives artesunate and

  2. Tetrapyrrole Signaling in Plants

    Directory of Open Access Journals (Sweden)

    Robert M. Larkin

    2016-10-01

    Full Text Available Tetrapyrroles make critical contributions to a number of important processes in diverse organisms. In plants, tetrapyrroles are essential for light signaling, the detoxification of reactive oxygen species, the assimilation of nitrate and sulfate, respiration, photosynthesis, and programed cell death. Thus, it is not surprising that tetrapyrrole metabolism is strictly regulated and that tetrapyrrole metabolism affects signaling mechanisms that regulate gene expression. In plants and algae, tetrapyrroles are synthesized in plastids and were some of the first plastid signals demonstrated to regulate nuclear gene expression. In plants, the mechanism of tetrapyrrole-dependent plastid-to-nucleus signaling remains poorly understood. Additionally, some of experiments that tested ideas for possible signaling mechanisms appeared to produce conflicting data. In some instances, these conflicts are potentially explained by different experimental conditions. Although the biological function of tetrapyrrole signaling is poorly understood, there is compelling evidence that this signaling is significant. Specifically, this signaling appears to affect the accumulation of starch and may promote abiotic stress tolerance. Tetrapyrrole-dependent plastid-to-nucleus signaling interacts with a distinct plastid-to-nucleus signaling mechanism that depends on GENOMES UNCUOPLED1 (GUN1. GUN1 contributes to a variety of processes, such as chloroplast biogenesis, the circadian rhythm, abiotic stress tolerance, and development. Thus, the contribution of tetrapyrrole signaling to plant function is potentially broader than we currently appreciate. In this review, I discuss these aspects of tetrapyrrole signaling.

  3. Growth factor signalling

    NARCIS (Netherlands)

    De Laat, SW; Boonstra, J; Defize, LHK; Kruijer, W; Van der Saag, PT; Tertoolen, LGJ; Van Zoelen, JJ; Den Hertog, J

    1999-01-01

    Signalling between cells in the developing vertebrate embryo is essential for nomal embryonic development. In the mid 1970's, signal transduction research started at the Hubrecht Laboratory with special emphasis on analysis of the signalling mechanisms that direct cell proliferation and

  4. Seismic communication signals in the blind mole-rat (Spalax ehrenbergi): electrophysiological and behavioral evidence for their processing by the auditory system.

    Science.gov (United States)

    Rado, R; Terkel, J; Wollberg, Z

    1998-10-01

    Based on morphological and behavioral findings we suggest that the seismic vibratory signals that blind mole-rats (Spalax ehrenbergi) use for intraspecific communication are picked up from the substrate by bone conduction and processed by the auditory system. An alternative hypothesis, raised by others, suggest that these signals are processed by the somatosensory system. We show here that brain stem and middle latency responses evoked by vibrations are similar to those evoked by high-intensity airborne clicks but are larger in their amplitudes, especially when the lower jaw is in close contact with the vibrating substrate. Bilateral deafening of the mole-rat or high-intensity masking noise almost completely eliminated these responses. Deafening also gradually reduced head-drumming behavior until its complete elimination about 4-6 weeks after surgery. Successive vibrations, at a rate of 0.5 vibrations/s, elicited prominent responses. At rates higher than 2 vibrations/s the amplitude of the brain stem response did not change, yet the middle latency response disappeared almost completely. It is concluded that the seismic signals that mole rate use for long distance communication are indeed processed primarily by the auditory system.

  5. The Ungraded Derived Category

    OpenAIRE

    Stai, Torkil Utvik

    2012-01-01

    By means of the ungraded derived category we prove that the orbit category of the bounded derived category of an iterated tilted algebra with respect to translation is triangulated in such a way that the canonical functor from the bounded derived category to the orbit category becomes a triangle functor.

  6. The Signal Distribution System

    CERN Document Server

    Belohrad, D; CERN. Geneva. AB Department

    2005-01-01

    For the purpose of LHC signal observation and high frequency signal distribution, the Signal Distribution System (SDS) was built. The SDS can contain up to 5 switching elements, where each element allows the user to switch between one of the maximum 8 bi-directional signals. The coaxial relays are used to switch the signals. Depending of the coaxial relay type used, the transfer bandwidth can go up to 18GHz. The SDS is controllable via TCP/IP, parallel port, or locally by rotary switch.

  7. Taxation of Derivatives

    DEFF Research Database (Denmark)

    Dyppel, Katja Joo

    2013-01-01

    The main objective for this thesis is to analyse and systematise the Danish legislation on taxation of derivatives. According to financial terminology, a derivative is a financial instrument. Its value is derived from changes in the value of one or more underlying assets.The most common derivatives...... with the scope of sections 29-33 of the Danish Act on Taxation of Gains and Losses on Claims and Debt and the tax consequences for the covered financial contracts. In the analysis of taxation of derivatives, the fundamental issues of qualification and tax treatment of the instruments are dealt with....... are known as futures, forwards, options and swaps. Derivatives are traded for the purpose of hedging financial or business risk, speculating in future spot prices and taking advantage of arbitrage opportunities. This market has increased tremendously in recent years. The term derivative is not used...

  8. Surface light scattering: integrated technology and signal processing

    DEFF Research Database (Denmark)

    Lading, L.; Dam-Hansen, C.; Rasmussen, E.

    1997-01-01

    systems representing increasing levels of integration are considered. It is demonstrated that efficient signal and data processing can be achieved by evaluation of the statistics of the derivative of the instantaneous phase of the detector signal. (C) 1997 Optical Society of America....

  9. Effects Of Asymmetry Of NRZ Data Signals On Performance

    Science.gov (United States)

    Nguyen, Tien M.

    1992-01-01

    Report presents theoretical analysis of effects of asymmetry in binary non-return-to-zero (NRZ) data signals upon performance of radiotelemetry system. Simple mathematical model predicting overall degradation of bit signal-to-noise ratio of telemetry system derived. Shows degradation increases with asymmetry.

  10. Phosphorelays provide tunable signal processing capabilities for the cell

    DEFF Research Database (Denmark)

    Kothamachu, Varun B; Feliu, Elisenda; Wiuf, Carsten

    2013-01-01

    present here this relation for four-layered phosphorelays, which are signaling systems that are ubiquitous in prokaryotes and also found in lower eukaryotes and plants. We derive an analytical expression that relates the shape of the signal-response relationship in a relay to the kinetic rates of forward...

  11. Ramanujan subspace pursuit for signal periodic decomposition

    Science.gov (United States)

    Deng, Shi-Wen; Han, Ji-Qing

    2017-06-01

    The period estimation and periodic decomposition of a signal represent long-standing problems in the field of signal processing and biomolecular sequence analysis. To address such problems, we introduce the Ramanujan subspace pursuit (RSP) based on the Ramanujan subspace. As a greedy iterative algorithm, the RSP can uniquely decompose any signal into a sum of exactly periodic components by selecting and removing the most dominant periodic component from the residual signal in each iteration. In the RSP, a novel periodicity metric is derived based on the energy of the exactly periodic component obtained by orthogonally projecting the residual signal into the Ramanujan subspace. The metric is then used to select the most dominant periodic component in each iteration. To reduce the computational cost of the RSP, we also propose the fast RSP (FRSP) based on the relationship between the periodic subspace and the Ramanujan subspace and based on the maximum likelihood estimation of the energy of the periodic component in the periodic subspace. The fast RSP has a lower computational cost and can decompose a signal of length N into a sum of K exactly periodic components in O (KNlogN) . In short, the main contributions of this paper are threefold: First, we present the RSP algorithm for decomposing a signal into its periodic components and theoretically prove the convergence of the algorithm based on the Ramanujan subspaces. Second, we present the FRSP algorithm, which is used to reduce the computational cost. Finally, we derive a periodic metric to measure the periodicity of the hidden periodic components of a signal. In addition, our results show that the RSP outperforms current algorithms for period estimation.

  12. Superluminal Signal Velocity

    OpenAIRE

    Nimtz, Guenter

    1998-01-01

    It recently has been demonstrated that signals conveyed by evanescent modes can travel faster than light. In this report some special features of signals are introduced and investigated, for instance the fundamental property that signals are frequency band limited. Evanescent modes are characterized by extraordinary properties: Their energy is {\\it negative}, they are not directly measurable, and the evanescent region is not causal since the modes traverse this region instantaneously. The stu...

  13. Noncausal Superluminal Nonlocal Signalling

    OpenAIRE

    Srikanth, R.

    1999-01-01

    We propose a thought experiment for classical superluminal signal transmission based on the quantum nonlocal influence of photons on their momentum entangled EPR twins. The signal sender measures either position or momentum of particles in a pure ensemble of the entangled pairs, leaving their twins as localized particles or plane waves. The signal receiver distinguishes these outcomes interferometrically using a double slit interferometer modified by a system of optical filters. Since the col...

  14. Higher derivative mimetic gravity

    Science.gov (United States)

    Gorji, Mohammad Ali; Mansoori, Seyed Ali Hosseini; Firouzjahi, Hassan

    2018-01-01

    We study cosmological perturbations in mimetic gravity in the presence of classified higher derivative terms which can make the mimetic perturbations stable. We show that the quadratic higher derivative terms which are independent of curvature and the cubic higher derivative terms which come from curvature corrections are sufficient to remove instabilities in mimetic perturbations. The classified higher derivative terms have the same dimensions but they contribute differently in the background and perturbed equations. Therefore, we can control both the background and the perturbation equations allowing us to construct the higher derivative extension of mimetic dark matter and the mimetic nonsingular bouncing scenarios. The latter can be thought as a new higher derivative effective action for the loop quantum cosmology scenario in which the equations of motion coincide with those suggested by loop quantum cosmology. We investigate a possible connection between the mimetic cosmology and the Randall-Sundrum cosmology.

  15. Temporal differentiation of optical signals using resonant gratings.

    Science.gov (United States)

    Bykov, Dmitry A; Doskolovich, Leonid L; Soifer, Viktor A

    2011-09-01

    We study theoretically the possibility of performing temporal differentiation of optical signals using a resonant diffraction grating. We demonstrate that the resonant grating allows the calculation of the first-order derivative of an optical signal envelope in the vicinity of waveguide resonant frequencies in the zeroth transmitted diffraction order. The grating is shown to allow the calculation of the fractional derivative of order 1/2 in the vicinity of Rayleigh-Wood anomalies. Numerical simulations based on the rigorous coupled-wave analysis of Maxwell's equations demonstrate the high-quality differentiation of optical signals with temporal features in the picosecond range.

  16. Derivative actions in China

    OpenAIRE

    Lin, Shaowei

    2014-01-01

    The enactment of derivative action was expected to be actively used by shareholders to protect their interests. In fact, it turned out that this reform effort seemed futile as the right to engage in such actions was rarely exercised. This raises a question about the role of derivative actions in China; namely, should a derivative action system play a key role in protecting shareholder interests? If the answer is positive, the next question is how such a system could be improved...

  17. Global Derivatives Market

    Directory of Open Access Journals (Sweden)

    Stankovska Aleksandra

    2017-06-01

    Full Text Available Globalization of financial markets led to the enormous growth of volume and diversification of financial transactions. Financial derivatives were the basic elements of this growth. Derivatives play a useful and important role in hedging and risk management, but they also pose several dangers to the stability of financial markets and thereby the overall economy. Derivatives are used to hedge and speculate the risk associated with commerce and finance.

  18. Digital signal processing

    CERN Document Server

    O'Shea, Peter; Hussain, Zahir M

    2011-01-01

    In three parts, this book contributes to the advancement of engineering education and that serves as a general reference on digital signal processing. Part I presents the basics of analog and digital signals and systems in the time and frequency domain. It covers the core topics: convolution, transforms, filters, and random signal analysis. It also treats important applications including signal detection in noise, radar range estimation for airborne targets, binary communication systems, channel estimation, banking and financial applications, and audio effects production. Part II considers sel

  19. Biomedical signals and systems

    CERN Document Server

    Tranquillo, Joseph V

    2013-01-01

    Biomedical Signals and Systems is meant to accompany a one-semester undergraduate signals and systems course. It may also serve as a quick-start for graduate students or faculty interested in how signals and systems techniques can be applied to living systems. The biological nature of the examples allows for systems thinking to be applied to electrical, mechanical, fluid, chemical, thermal and even optical systems. Each chapter focuses on a topic from classic signals and systems theory: System block diagrams, mathematical models, transforms, stability, feedback, system response, control, time

  20. Endohedral Metallofullerene Derivatives

    Science.gov (United States)

    Dorn, Harry C. (Inventor); Iezzi, Erick B. (Inventor); Duchamp, James (Inventor)

    2008-01-01

    Trimetallic nitride endohedral metallofullerene derivatives and their preparation are described. The trimetallic nitride endohedral metallofullerene derivatives have the general formula A(sub 3-n)X(sub n)@C(sub m)(R) where n ranges from 0 to 3, A and X may be trivalent metals and may be either rare earth metal or group IIIB metals, m is between about 60 and about 200, and R is preferably an organic group. Derivatives where the R group forms cyclized derivatives with the fullerene cage are also described.

  1. Seafloor backscatter signal simulation and classification

    Digital Repository Service at National Institute of Oceanography (India)

    Mahale, V.; El Dine, W.G.; Chakraborty, B.

    in the backscattered signal. An analysis of the signal envelope fluctuation over several pings can be used to understand the roughness characteristics of the seafloor. In this, primary effort towards classification, we have concentrated only on the normal incidence... in such situations is to use the ground truth data to derive the type of class. Most of these problems are of supervised learning type, i.e. it requires examples of known class types, for the network learning process. In a typical scenario, a neural network...

  2. The Hedgehog Signal Induced Modulation of Bone Morphogenetic Protein Signaling: An Essential Signaling Relay for Urinary Tract Morphogenesis

    Science.gov (United States)

    Nakagata, Naomi; Miyagawa, Shinichi; Suzuki, Kentaro; Kitazawa, Sohei; Yamada, Gen

    2012-01-01

    Background Congenital diseases of the urinary tract are frequently observed in infants. Such diseases present a number of developmental anomalies such as hydroureter and hydronephrosis. Although some genetically-modified mouse models of growth factor signaling genes reproduce urinary phenotypes, the pathogenic mechanisms remain obscure. Previous studies suggest that a portion of the cells in the external genitalia and bladder are derived from peri-cloacal mesenchymal cells that receive Hedgehog (Hh) signaling in the early developmental stages. We hypothesized that defects in such progenitor cells, which give rise to urinary tract tissues, may be a cause of such diseases. Methodology/Principal Findings To elucidate the pathogenic mechanisms of upper urinary tract malformations, we analyzed a series of Sonic hedgehog (Shh) deficient mice. Shh−/− displayed hydroureter and hydronephrosis phenotypes and reduced expression of several developmental markers. In addition, we suggested that Shh modulation at an early embryonic stage is responsible for such phenotypes by analyzing the Shh conditional mutants. Tissue contribution assays of Hh-responsive cells revealed that peri-cloacal mesenchymal cells, which received Hh signal secreted from cloacal epithelium, could contribute to the ureteral mesenchyme. Gain- and loss-of-functional mutants for Hh signaling revealed a correlation between Hh signaling and Bone morphogenetic protein (Bmp) signaling. Finally, a conditional ablation of Bmp receptor type IA (BmprIA) gene was examined in Hh-responsive cell lineages. This system thus made it possible to analyze the primary functions of the growth factor signaling relay. The defective Hh-to-Bmp signaling relay resulted in severe urinary tract phenotypes with a decrease in the number of Hh-responsive cells. Conclusions/Significance This study identified the essential embryonic stages for the pathogenesis of urinary tract phenotypes. These results suggested that Hh

  3. Signal quality and Bayesian signal processing in neurofeedback based on real-time fMRI.

    Science.gov (United States)

    Koush, Yury; Zvyagintsev, Mikhail; Dyck, Miriam; Mathiak, Krystyna A; Mathiak, Klaus

    2012-01-02

    Real-time fMRI allows analysis and visualization of the brain activity online, i.e. within one repetition time. It can be used in neurofeedback applications where subjects attempt to control an activation level in a specified region of interest (ROI) of their brain. The signal derived from the ROI is contaminated with noise and artifacts, namely with physiological noise from breathing and heart beat, scanner drift, motion-related artifacts and measurement noise. We developed a Bayesian approach to reduce noise and to remove artifacts in real-time using a modified Kalman filter. The system performs several signal processing operations: subtraction of constant and low-frequency signal components, spike removal and signal smoothing. Quantitative feedback signal quality analysis was used to estimate the quality of the neurofeedback time series and performance of the applied signal processing on different ROIs. The signal-to-noise ratio (SNR) across the entire time series and the group event-related SNR (eSNR) were significantly higher for the processed time series in comparison to the raw data. Applied signal processing improved the t-statistic increasing the significance of blood oxygen level-dependent (BOLD) signal changes. Accordingly, the contrast-to-noise ratio (CNR) of the feedback time series was improved as well. In addition, the data revealed increase of localized self-control across feedback sessions. The new signal processing approach provided reliable neurofeedback, performed precise artifacts removal, reduced noise, and required minimal manual adjustments of parameters. Advanced and fast online signal processing algorithms considerably increased the quality as well as the information content of the control signal which in turn resulted in higher contingency in the neurofeedback loop. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Signal sampling circuit

    NARCIS (Netherlands)

    Louwsma, S.M.; Vertregt, Maarten

    2011-01-01

    A sampling circuit for sampling a signal is disclosed. The sampling circuit comprises a plurality of sampling channels adapted to sample the signal in time-multiplexed fashion, each sampling channel comprising a respective track-and-hold circuit connected to a respective analogue to digital

  5. Signal sampling circuit

    NARCIS (Netherlands)

    Louwsma, S.M.; Vertregt, Maarten

    2010-01-01

    A sampling circuit for sampling a signal is disclosed. The sampling circuit comprises a plurality of sampling channels adapted to sample the signal in time-multiplexed fashion, each sampling channel comprising a respective track-and-hold circuit connected to a respective analogue to digital

  6. Ubiquitination in apoptosis signaling

    NARCIS (Netherlands)

    van de Kooij, L.W.

    2014-01-01

    The work described in this thesis focuses on ubiquitination and protein degradation, with an emphasis on how these processes regulate apoptosis signaling. More specifically, our aims were: 1. To increase the understanding of ubiquitin-mediated regulation of apoptosis signaling. 2. To identify the E3

  7. SignalR blueprints

    CERN Document Server

    Ingebrigtsen, Einar

    2015-01-01

    This book is designed for software developers, primarily those with knowledge of C#, .NET, and JavaScript. Good knowledge and understanding of SignalR is assumed to allow efficient programming of core elements and applications in SignalR.

  8. Optimal fault signal estimation

    NARCIS (Netherlands)

    Stoorvogel, Antonie Arij; Niemann, H.H.; Saberi, A.; Sannuti, P.

    2002-01-01

    We consider here both fault identification and fault signal estimation. Regarding fault identification, we seek either exact or almost fault identification. On the other hand, regarding fault signal estimation, we seek either $H_2$ optimal, $H_2$ suboptimal or Hinfinity suboptimal estimation. By

  9. Multiresolution signal decomposition schemes

    NARCIS (Netherlands)

    J. Goutsias (John); H.J.A.M. Heijmans (Henk)

    1998-01-01

    textabstract[PNA-R9810] Interest in multiresolution techniques for signal processing and analysis is increasing steadily. An important instance of such a technique is the so-called pyramid decomposition scheme. This report proposes a general axiomatic pyramid decomposition scheme for signal analysis

  10. The Dangers of Derivatives.

    Science.gov (United States)

    Blumenstyk, Goldie

    1994-01-01

    Heavy investment in derivatives, whose value derives from the price movement of some underlying security, has meant heavy losses for some colleges and universities despite the fact that institutional investors are required to assure that they understand the risks of such investment. (MSE)

  11. A Generalized Demodulation and Hilbert Transform Based Signal Decomposition Method

    Directory of Open Access Journals (Sweden)

    Zhi-Xiang Hu

    2017-01-01

    Full Text Available This paper proposes a new signal decomposition method that aims to decompose a multicomponent signal into monocomponent signal. The main procedure is to extract the components with frequencies higher than a given bisecting frequency by three steps: (1 the generalized demodulation is used to project the components with lower frequencies onto negative frequency domain, (2 the Hilbert transform is performed to eliminate the negative frequency components, and (3 the inverse generalized demodulation is used to obtain the signal which contains components with higher frequencies only. By running the procedure recursively, all monocomponent signals can be extracted efficiently. A comprehensive derivation of the decomposition method is provided. The validity of the proposed method has been demonstrated by extensive numerical analysis. The proposed method is also applied to decompose the dynamic strain signal of a cable-stayed bridge and the echolocation signal of a bat.

  12. Neutron signal transfer analysis

    CERN Document Server

    Pleinert, H; Lehmann, E

    1999-01-01

    A new method called neutron signal transfer analysis has been developed for quantitative determination of hydrogenous distributions from neutron radiographic measurements. The technique is based on a model which describes the detector signal obtained in the measurement as a result of the action of three different mechanisms expressed by signal transfer functions. The explicit forms of the signal transfer functions are determined by Monte Carlo computer simulations and contain only the distribution as a variable. Therefore an unknown distribution can be determined from the detector signal by recursive iteration. This technique provides a simple and efficient tool for analysis of this type while also taking into account complex effects due to the energy dependency of neutron interaction and single and multiple scattering. Therefore this method provides an efficient tool for precise quantitative analysis using neutron radiography, as for example quantitative determination of moisture distributions in porous buil...

  13. Acoustic Signals and Systems

    DEFF Research Database (Denmark)

    2008-01-01

    The Handbook of Signal Processing in Acoustics will compile the techniques and applications of signal processing as they are used in the many varied areas of Acoustics. The Handbook will emphasize the interdisciplinary nature of signal processing in acoustics. Each Section of the Handbook...... will present topics on signal processing which are important in a specific area of acoustics. These will be of interest to specialists in these areas because they will be presented from their technical perspective, rather than a generic engineering approach to signal processing. Non-specialists, or specialists...... from different areas, will find the self-contained chapters accessible and will be interested in the similarities and differences between the approaches and techniques used in different areas of acoustics....

  14. Molecular and Cellular Signaling

    CERN Document Server

    Beckerman, Martin

    2005-01-01

    A small number of signaling pathways, no more than a dozen or so, form a control layer that is responsible for all signaling in and between cells of the human body. The signaling proteins belonging to the control layer determine what kinds of cells are made during development and how they function during adult life. Malfunctions in the proteins belonging to the control layer are responsible for a host of human diseases ranging from neurological disorders to cancers. Most drugs target components in the control layer, and difficulties in drug design are intimately related to the architecture of the control layer. Molecular and Cellular Signaling provides an introduction to molecular and cellular signaling in biological systems with an emphasis on the underlying physical principles. The text is aimed at upper-level undergraduates, graduate students and individuals in medicine and pharmacology interested in broadening their understanding of how cells regulate and coordinate their core activities and how diseases ...

  15. Signal velocity in oscillator arrays

    Science.gov (United States)

    Cantos, C. E.; Veerman, J. J. P.; Hammond, D. K.

    2016-09-01

    We investigate a system of coupled oscillators on the circle, which arises from a simple model for behavior of large numbers of autonomous vehicles where the acceleration of each vehicle depends on the relative positions and velocities between itself and a set of local neighbors. After describing necessary and sufficient conditions for asymptotic stability, we derive expressions for the phase velocity of propagation of disturbances in velocity through this system. We show that the high frequencies exhibit damping, which implies existence of well-defined signal velocitiesc+ > 0 and c- < 0 such that low frequency disturbances travel through the flock as f+(x - c+t) in the direction of increasing agent numbers and f-(x - c-t) in the other.

  16. Fault diagnosis of planetary gearboxes via torsional vibration signal analysis

    Science.gov (United States)

    Feng, Zhipeng; Zuo, Ming J.

    2013-04-01

    Torsional vibration signals are theoretically free from the amplitude modulation effect caused by time variant vibration transfer paths due to the rotation of planet carrier and sun gear, and therefore their spectral structure are simpler than transverse vibration signals. Thus, it is potentially easy and effective to diagnose planetary gearbox faults via torsional vibration signal analysis. We give explicit equations to model torsional vibration signals, considering both distributed gear faults (like manufacturing or assembly errors) and local gear faults (like pitting, crack or breakage of one tooth), and derive the characteristics of both the traditional Fourier spectrum and the proposed demodulated spectra of amplitude envelope and instantaneous frequency. These derivations are not only effective to diagnose single gear fault of planetary gearboxes, but can also be generalized to detect and locate multiple gear faults. We validate experimentally the signal models, as well as the Fourier spectral analysis and demodulation analysis methods.

  17. Biological nitric oxide signalling: chemistry and terminology.

    Science.gov (United States)

    Heinrich, Tassiele A; da Silva, Roberto S; Miranda, Katrina M; Switzer, Christopher H; Wink, David A; Fukuto, Jon M

    2013-08-01

    Biological nitrogen oxide signalling and stress is an area of extreme clinical, pharmacological, toxicological, biochemical and chemical research interest. The utility of nitric oxide and derived species as signalling agents is due to their novel and vast chemical interactions with a variety of biological targets. Herein, the chemistry associated with the interaction of the biologically relevant nitrogen oxide species with fundamental biochemical targets is discussed. Specifically, the chemical interactions of nitrogen oxides with nucleophiles (e.g. thiols), metals (e.g. hemeproteins) and paramagnetic species (e.g. dioxygen and superoxide) are addressed. Importantly, the terms associated with the mechanisms by which NO (and derived species) react with their respective biological targets have been defined by numerous past chemical studies. Thus, in order to assist researchers in referring to chemical processes associated with nitrogen oxide biology, the vernacular associated with these chemical interactions is addressed. © 2013 The British Pharmacological Society.

  18. Biological nitric oxide signalling: chemistry and terminology

    Science.gov (United States)

    Heinrich, Tassiele A; da Silva, Roberto S; Miranda, Katrina M; Switzer, Christopher H; Wink, David A; Fukuto, Jon M

    2013-01-01

    Biological nitrogen oxide signalling and stress is an area of extreme clinical, pharmacological, toxicological, biochemical and chemical research interest. The utility of nitric oxide and derived species as signalling agents is due to their novel and vast chemical interactions with a variety of biological targets. Herein, the chemistry associated with the interaction of the biologically relevant nitrogen oxide species with fundamental biochemical targets is discussed. Specifically, the chemical interactions of nitrogen oxides with nucleophiles (e.g. thiols), metals (e.g. hemeproteins) and paramagnetic species (e.g. dioxygen and superoxide) are addressed. Importantly, the terms associated with the mechanisms by which NO (and derived species) react with their respective biological targets have been defined by numerous past chemical studies. Thus, in order to assist researchers in referring to chemical processes associated with nitrogen oxide biology, the vernacular associated with these chemical interactions is addressed. PMID:23617570

  19. Reaction network analysis in biochemical signaling pathways

    OpenAIRE

    Martinez-Forero, I. (Iván); Pelaez, A. (Antonio); Villoslada, P. (Pablo)

    2010-01-01

    The aim of this thesis is to improve the understanding of signaling pathways through a theoretical study of chemical reaction networks. The equilibirum solution to the equations derived from chemical networks will be analytically resolved using tools from algebraic geometry. The chapters are organized as follows: 1. An introduction to chemical dynamics in biological systems with a special emphasis on steady state analysis 2. Complete description of the chemical reaction network theor...

  20. Generation of octupled microwave signal via frequency multiplication method

    Science.gov (United States)

    Singh, Mandeep; Raghuwanshi, Sanjeev Kumar

    2017-11-01

    We propose experimentally a technique to generate a low noise frequency octupled microwave signal. We demonstrate that by carefully arranging the phase of 90° between two MZMs (out of three), a low noise photonically assisted octupled microwave signal can be generated. A 25.6 GHz optical microwave signal is achieved with 3.2 GHz of local RF oscillator signal. Moreover, the intensity expressions at the output of photodiode are derived for both with and without dispersion terms. Finally, we advocate the impact of the electrical spurious suppression ratio on the extinction ratio of the modulators. Our experimental and simulation results agree well with the theoretical analysis.

  1. Source Signals Separation and Reconstruction Following Principal Component Analysis

    Directory of Open Access Journals (Sweden)

    WANG Cheng

    2014-02-01

    Full Text Available For separation and reconstruction of source signals from observed signals problem, the physical significance of blind source separation modal and independent component analysis is not very clear, and its solution is not unique. Aiming at these disadvantages, a new linear and instantaneous mixing model and a novel source signals separation reconstruction solving method from observed signals based on principal component analysis (PCA are put forward. Assumption of this new model is statistically unrelated rather than independent of source signals, which is different from the traditional blind source separation model. A one-to-one relationship between linear and instantaneous mixing matrix of new model and linear compound matrix of PCA, and a one-to-one relationship between unrelated source signals and principal components are demonstrated using the concept of linear separation matrix and unrelated of source signals. Based on this theoretical link, source signals separation and reconstruction problem is changed into PCA of observed signals then. The theoretical derivation and numerical simulation results show that, in despite of Gauss measurement noise, wave form and amplitude information of unrelated source signal can be separated and reconstructed by PCA when linear mixing matrix is column orthogonal and normalized; only wave form information of unrelated source signal can be separated and reconstructed by PCA when linear mixing matrix is column orthogonal but not normalized, unrelated source signal cannot be separated and reconstructed by PCA when mixing matrix is not column orthogonal or linear.

  2. Signal flow analysis

    CERN Document Server

    Abrahams, J R; Hiller, N

    1965-01-01

    Signal Flow Analysis provides information pertinent to the fundamental aspects of signal flow analysis. This book discusses the basic theory of signal flow graphs and shows their relation to the usual algebraic equations.Organized into seven chapters, this book begins with an overview of properties of a flow graph. This text then demonstrates how flow graphs can be applied to a wide range of electrical circuits that do not involve amplification. Other chapters deal with the parameters as well as circuit applications of transistors. This book discusses as well the variety of circuits using ther

  3. Signaling molecules: hydrogen sulfide and polysulfide.

    Science.gov (United States)

    Kimura, Hideo

    2015-02-10

    Hydrogen sulfide (H2S) has been recognized as a signaling molecule as well as a cytoprotectant. It modulates neurotransmission, regulates vascular tone, and protects various tissues and organs, including neurons, the heart, and kidneys, from oxidative stress and ischemia-reperfusion injury. H2S is produced from l-cysteine by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST) along with cysteine aminotransferase. In addition to these enzymes, we recently identified a novel pathway to produce H2S from d-cysteine, which involves d-amino acid oxidase (DAO) along with 3MST. These enzymes are localized in the cytoplasm, mitochondria, and peroxisomes. However, some enzymes translocate to organelles under specific conditions. Moreover, H2S-derived potential signaling molecules such as polysulfides and HSNO have been identified. The physiological stimulations, which trigger the production of H2S and its derivatives and maintain their local levels, remain unclear. Understanding the regulation of the H2S production and H2S-derived signaling molecules and the specific stimuli that induce their release will provide new insights into the biology of H2S and therapeutic development in diseases involving these substances.

  4. The Ubiquitin System and Jasmonate Signaling

    Directory of Open Access Journals (Sweden)

    Astrid Nagels Durand

    2016-01-01

    Full Text Available The ubiquitin (Ub system is involved in most, if not all, biological processes in eukaryotes. The major specificity determinants of this system are the E3 ligases, which bind and ubiquitinate specific sets of proteins and are thereby responsible for target recruitment to the proteasome or other cellular processing machineries. The Ub system contributes to the regulation of the production, perception and signal transduction of plant hormones. Jasmonic acid (JA and its derivatives, known as jasmonates (JAs, act as signaling compounds regulating plant development and plant responses to various biotic and abiotic stress conditions. We provide here an overview of the current understanding of the Ub system involved in JA signaling.

  5. ASTEROID LIGHTCURVE DERIVED DATA

    Data.gov (United States)

    National Aeronautics and Space Administration — This is a compilation of published rotational parameters derived from lightcurve data for asteroids, based on the Warner et al. (2009) Asteroid Lightcurve Database....

  6. Teaching Cournot without Derivatives.

    Science.gov (United States)

    Dufwenberg, Martin

    2001-01-01

    Presents a simple technique for teaching the Cournot model to first-year microeconomic students. Involves demonstrating, without the use of derivatives, that out of all rectangles with a common perimeter, the square has the greatest area. (RLH)

  7. The azobenzene derivatives

    Science.gov (United States)

    Ionita, Ionica; Radulescu, Cristiana; Poinescu, Aurora Anca; Anghelina, Florina Violeta; Bunghez, Raluca; Ion, Rodica-Mariana

    2015-02-01

    Azobenzene derivatives constitute a group of dyes which have photochromic properties and have been investigated as promising systems for diverse applications in the unconventional optic area, their properties can be moulded with help of light.

  8. Amphetamine derivative related deaths.

    Science.gov (United States)

    Lora-Tamayo, C; Tena, T; Rodríguez, A

    1997-02-28

    Amphetamine its methylendioxy (methylendioxyamphetamine methylenedioxymethylamphetamine, methylenedioxyethylamphetamine) and methoxy derivatives (p-methoxyamphetamine and p-methoxymethylamphetamine) are widely abused in Spanish society. We present here the results of a systematic study of all cases of deaths brought to the attention of the Madrid department of the Instituto Nacional de Toxicologia from 1993 to 1995 in which some of these drugs have been found in the cadaveric blood. The cases were divided into three categories: amphetamine and derivatives, amphetamines and alcohol, amphetamines and other drugs. Data on age, sex, clinical symptoms, morphological findings, circumstances of death, when known, and concentration of amphetamine derivatives, alcohol and other drugs in blood are given for each group. The information provided here may prove to be useful for the forensic interpretation of deaths which are directly or indirectly related to abuse of amphetamine derivatives.

  9. Signal Station Inspection Reports

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Handwritten reports resulting from detailed inspections of US Army Signal Service Stations, 1871-1889. Features reported included instrument exposure and condition,...

  10. Transmembrane Signalling: Membrane messengers

    Science.gov (United States)

    Cockroft, Scott L.

    2017-05-01

    Life has evolved elaborate means of communicating essential chemical information across cell membranes. Inspired by biology, two new artificial mechanisms have now been developed that use synthetic messenger molecules to relay chemical signals into or across lipid membranes.

  11. Topological signal processing

    CERN Document Server

    Robinson, Michael

    2014-01-01

    Signal processing is the discipline of extracting information from collectio