WorldWideScience

Sample records for hydraulic jet notching

  1. A novel design of semi-active hydraulic mount with wide-band tunable notch frequency

    Science.gov (United States)

    Wang, Min; Yao, Guo-feng; Zhao, Jing-zhou; Qin, Min

    2014-04-01

    Hydraulic engine mount is advanced vibration isolator with superior performance to reduce vibration transferred from engine to chassis. As the stiffness at notch frequency is small, some semi-active or active hydraulic mounts tune some parameters to let notch frequency coincide with exciting frequency for better vibration isolation performance. It is discovered the current semi-active mounts can tune the notch frequency in narrow frequency band when only one parameter is tuned. A novel semi-active hydraulic engine mount design which introduces screw thread is proposed and researched in the paper. This hydraulic mount can control both cross section area and the length of inertia track and the theoretical tunable notch frequency band is [0, ∞). Theoretical work is carried out to uncover the capability for the proposed design to tune notch frequency. Simulation work is performed to understand its high vibration isolation performance. For the purpose of energy conservation, the friction self-locking is introduced. This denotes once the mount is tuned at optimal condition, the energy can be cut off and the optimal condition will never change. We also determine the best time to tune the parameters of the proposed mount in order to decrease the acting force. The proposed semi-active mount has capability to obtain wide band tunable notch frequency and has merit of energy conservation.

  2. Turbulent jets issuing from rectangular nozzle with a rectangular notch at the midspan

    Science.gov (United States)

    Fujita, Shigetaka; Harima, Takashi; Osaka, Hideo

    2012-04-01

    The turbulent flowfield of turbulent jet issuing from rectangular nozzle (Aspect Ratio=12.5) with a rectangular notch at the midspan, has been investigated experimentally. Four aspect ratios of rectangular notch (NAR: Notch Aspect Ratio) used in this experiment were 2.5, 7.5, 12.5 and 165. The Reynolds number based on the nozzle width d and the exit mean velocity Ue, was kept constant 30000 (NAR=2.5 and 7.5), 15000 (NAR=12.5) and 13000 (NAR=165), respectively. Longitudinal mean velocity and turbulent intensities were measured using an X-array Hot-Wire Probe (5 µm in diameter, 1 mm effective length) operated by the linearized constant temperature anemometers (DANTEC), and the spanwise and the lateral mean velocities were measured using a yaw meter. The signals from the anemometers were passed through the low-pass filters and sampled using A.D. converter. The processing of the signals was made by a personal computer. Acquisition time of the signals was usually 80 seconds. From this experiment, it was revealed that the attachment of a rectangular notch to the rectangular jet suppressed the development of the turbulent velocity scales near the jet centre in the upstream region for the cases of NAR≥7.5.

  3. Turbulent jets issuing from rectangular nozzle with a rectangular notch at the midspan

    Directory of Open Access Journals (Sweden)

    Osaka Hideo

    2012-04-01

    Full Text Available The turbulent flowfield of turbulent jet issuing from rectangular nozzle (Aspect Ratio=12.5 with a rectangular notch at the midspan, has been investigated experimentally. Four aspect ratios of rectangular notch (NAR: Notch Aspect Ratio used in this experiment were 2.5, 7.5, 12.5 and 165. The Reynolds number based on the nozzle width d and the exit mean velocity Ue, was kept constant 30000 (NAR=2.5 and 7.5, 15000 (NAR=12.5 and 13000 (NAR=165, respectively. Longitudinal mean velocity and turbulent intensities were measured using an X-array Hot-Wire Probe (5 µm in diameter, 1 mm effective length operated by the linearized constant temperature anemometers (DANTEC, and the spanwise and the lateral mean velocities were measured using a yaw meter. The signals from the anemometers were passed through the low-pass filters and sampled using A.D. converter. The processing of the signals was made by a personal computer. Acquisition time of the signals was usually 80 seconds. From this experiment, it was revealed that the attachment of a rectangular notch to the rectangular jet suppressed the development of the turbulent velocity scales near the jet centre in the upstream region for the cases of NAR≥7.5.

  4. Thermal-hydraulic modeling and analysis of spool valve with sloping U-shape notch by bond graph

    Institute of Scientific and Technical Information of China (English)

    娄磊; 吴万荣; 王兆强; 梁向京

    2015-01-01

    To increase the efficiency and reliability of the thermodynamics analysis of the spool valve, the precise function expression of the flow area for the sloping U-shape notch orifice versus the spool stroke and thermal-hydraulic bond graph based on the conservation of mass and energy were introduced. Subsequently, the connection rule for the bond graph elements and the method to construct the complete thermal-hydraulic system model were proposed. On the basis of heat transfer analysis of a typical hydraulic circuit containing the spool valve, the lumped parameter for mathematical model of the system was given. At last, the reliability of the mathematical model of the flow area and the thermal-hydraulic system for the sloping U-shape notch orifice on the spool were demonstrated by the test. The good agreement between the simulation results and experimental data demonstrates the validity of the modeling method.

  5. An Experimental Investigation of Hydraulic Jet Fracturing Technology with Coiled Tubing

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    To solve the increasingly serious problem of "many wells, but low productivity" in China, the hydraulic jetting fracturing technology with coiled tubing, as a new measure for effectively improving the production rate of individual well and enhancing oil and gas recovery, merits much attention nowa- days. On the basis of study of the hydraulic jetting fracturing mechanism with coiled tubing and numerical simulation of pressure distribution inside the pores, the mechanism of pressure rise inside the pores caused by the pressure boost action within the jetting pore and the hydraulic isolation action is examined, and the influence of main parameters on the pressure distribution inside the pores is analyzed. 3 kinds of operating methods of hydraulic jetting fracturing with coiled tubing are raised with the tubular diameter of coiled tub- ing as an important feature parameter. According to the experimental study, the fracturing mechanism and computational resuks of numerical simulation are both examined. It is considered that under the same pres- sure drop of jet nozzle, the pressure inside the pores increases with the confining pressure nearly at a line- ar state. When the vertical depth of the borehole is rather big and the rupture pressure of the formation is higher, it is recommended to use higher pressure drop of jet nozzle for achieving better pressure boost and hydraulic isolation effect. For the hydraulic jetting fracturing with coiled tubing, the coiled tubing with tu- bular diameter not less than 50. 8 mm (2 in. ) is usually used.

  6. Research on Discharge Circuit of Electro-Hydraulic Power Impulse Water Jets

    Science.gov (United States)

    Wang, Zhaohui; Gao, Quanjie; Wang, Wei; Liao, Zhenfang

    2012-01-01

    Electro-hydraulic power impulse water jets can convert the shock wave generated in the liquid by discharging into mechanical energy, and it has been widely used in material forming, surface cleaning, pipeline dirt cleaning and ore breaking process. Compared with the traditional high pressure water jets, the energy utilization of electro-hydraulic power impulse water jets is up to 80% while the water consumption is reduced by 40-55%. This paper has taken electro-hydraulic power impulse water jets as the research object, employed obtaining the maximum pressure of compression impulse matrix surface as the research goal, studied in depth the equivalent discharge circuit, characteristic equation and the relationship between the electrical parameters of the electro-hydraulic power impulse discharge circuit and built the calculation method of the voltage, the inductance, the capacitance and the electrode spacing parameter of electro-hydraulic power impulse water jets discharge circuit. So, it will provide important theoretical basis for further studies of electro-hydraulic power impulse technology and the existing water jets device.

  7. Study on Flow Field Characteristics of Nozzle Water Jet in Hydraulic cutting

    Science.gov (United States)

    Liao, Wen-tao; Deng, Xiao-yu

    2017-08-01

    Based on the theory of hydrodynamics, a mathematical model of nozzle water jet flow field in hydraulic cutting is established. By numerical simulation, the effects of nozzle convergence angle, nozzle outlet diameter and cylindrical section length on water jet flow impact is obtained, and the influence of three factors on the nozzle water jet flow field is analyzed. The optimal nozzle parameters are obtained by simulation as follows: convergence angle is 13 °, cylindrical section length is 8 mm and nozzle outlet diameter is 2 mm. Under this optimal nozzle parameters, hydraulic cutting has the best comprehensive effect.

  8. Combined Thermo-Hydraulic Analysis of a Cryogenic Jet

    CERN Document Server

    Chorowski, M

    1999-01-01

    A cryogenic jet is a phenomenon encountered in different fields like some technological processes and cryosurgery. It may also be a result of cryogenic equipment rupture or a cryogen discharge from the cryostats following resistive transition in superconducting magnets. Heat exchange between a cold jet and a warm steel element (e.g. a buffer tank wall or a transfer line vacuum vessel wall) may result in an excessive localisation of thermal strains and stresses. The objective of the analysis is to get a combined (analytical and experimental) one-dimensional model of a cryogenic jet that will enable estimation of heat transfer intensity between the jet and steel plate with a suitable accuracy for engineering applications. The jet diameter can only be determined experimentally. The mean velocity profile can be calculated from the fact that the total flux of momentum along the jet axis is conserved. The proposed model allows deriving the jet crown area with respect to the distance from the vent and the mean veloc...

  9. Comparisons of Hydraulic Performance in Permanent Maglev Pump for Water-Jet Propulsion

    Directory of Open Access Journals (Sweden)

    Puyu Cao

    2014-08-01

    Full Text Available The operation of water-jet propulsion can generate nonuniform inflow that may be detrimental to the performance of the water-jets. To reduce disadvantages of the nonuniform inflow, a rim-driven water-jet propulsion was designed depending on the technology of passive magnetic levitation. Insufficient understanding of large performance deviations between the normal water-jets (shaft and permanent maglev water-jets (shaftless is a major problem in this paper. CFD was directly adopted in the feasibility and superiority of permanent maglev water-jets. Comparison and discussion of the hydraulic performance were carried out. The shaftless duct firstly has a drop in hydraulic losses (K1, since it effectively avoids the formation and evolution of the instability secondary vortex by the normalized helicity analysis. Then, the shaftless intake duct improves the inflow field of the water-jet pump, with consequencing the drop in the backflow and blocking on the blade shroud. So that the shaftless water-jet pump delivers higher flow rate and head to the propulsion than the shaft. Eventually, not only can the shaftless model increase the thrust and efficiency, but it has the ability to extend the working range and broaden the high efficiency region as well.

  10. Feeding kinematics, suction, and hydraulic jetting performance of harbor seals (Phoca vitulina).

    Science.gov (United States)

    Marshall, Christopher D; Wieskotten, Sven; Hanke, Wolf; Hanke, Frederike D; Marsh, Alyssa; Kot, Brian; Dehnhardt, Guido

    2014-01-01

    The feeding kinematics, suction and hydraulic jetting capabilities of captive harbor seals (Phoca vitulina) were characterized during controlled feeding trials. Feeding trials were conducted using a feeding apparatus that allowed a choice between biting and suction, but also presented food that could be ingested only by suction. Subambient pressure exerted during suction feeding behaviors was directly measured using pressure transducers. The mean feeding cycle duration for suction-feeding events was significantly shorter (0.15±0.09 s; Pfeeding events (0.18±0.08 s). Subjects feeding in-water used both a suction and a biting feeding mode. Suction was the favored feeding mode (84% of all feeding events) compared to biting, but biting comprised 16% of feeding events. In addition, seals occasionally alternated suction with hydraulic jetting, or used hydraulic jetting independently, to remove fish from the apparatus. Suction and biting feeding modes were kinematically distinct regardless of feeding location (in-water vs. on-land). Suction was characterized by a significantly smaller gape (1.3±0.23 cm; Pforce recorded was 53.9 kPa. Suction and hydraulic jetting where employed 90.5% and 9.5%, respectively, during underwater feeding events. Harbor seals displayed a wide repertoire of behaviorally flexible feeding strategies to ingest fish from the feeding apparatus. Such flexibility of feeding strategies and biomechanics likely forms the basis of their opportunistic, generalized feeding ecology and concomitant breadth of diet.

  11. Feeding Kinematics, Suction, and Hydraulic Jetting Performance of Harbor Seals (Phoca vitulina)

    Science.gov (United States)

    Marshall, Christopher D.; Wieskotten, Sven; Hanke, Wolf; Hanke, Frederike D.; Marsh, Alyssa; Kot, Brian; Dehnhardt, Guido

    2014-01-01

    The feeding kinematics, suction and hydraulic jetting capabilities of captive harbor seals (Phoca vitulina) were characterized during controlled feeding trials. Feeding trials were conducted using a feeding apparatus that allowed a choice between biting and suction, but also presented food that could be ingested only by suction. Subambient pressure exerted during suction feeding behaviors was directly measured using pressure transducers. The mean feeding cycle duration for suction-feeding events was significantly shorter (0.15±0.09 s; Psuction and a biting feeding mode. Suction was the favored feeding mode (84% of all feeding events) compared to biting, but biting comprised 16% of feeding events. In addition, seals occasionally alternated suction with hydraulic jetting, or used hydraulic jetting independently, to remove fish from the apparatus. Suction and biting feeding modes were kinematically distinct regardless of feeding location (in-water vs. on-land). Suction was characterized by a significantly smaller gape (1.3±0.23 cm; PSuction and hydraulic jetting where employed 90.5% and 9.5%, respectively, during underwater feeding events. Harbor seals displayed a wide repertoire of behaviorally flexible feeding strategies to ingest fish from the feeding apparatus. Such flexibility of feeding strategies and biomechanics likely forms the basis of their opportunistic, generalized feeding ecology and concomitant breadth of diet. PMID:24475170

  12. Thermal-hydraulic performance of convective boiling jet array impingement

    Science.gov (United States)

    Jenkins, R.; De Brún, C.; Kempers, R.; Lupoi, R.; Robinson, A. J.

    2016-09-01

    Jet impingement boiling is investigated with regard to heat transfer and pressure drop performance using a novel laser sintered 3D printed jet impingement manifold design. Water was the working fluid at atmospheric pressure with inlet subcooling of 7oC. The convective boiling performance of the impinging jet system was investigated for a flat copper target surface for 2700≤Re≤5400. The results indicate that the heat transfer performance of the impinging jet is independent of Reynolds number for fully developed boiling. Also, the investigation of nozzle to plate spacing shows that low spacing delays the onset of nucleate boiling causing a superheat overshoot that is not observed with larger gaps. However, no sensitivity to the gap spacing was measured once boiling was fully developed. The assessment of the pressure drop performance showed that the design effectively transfers heat with low pumping power requirements. In particular, owing to the insensitivity of the heat transfer to flow rate during fully developed boiling, the coefficient of performance of jet impingement boiling in the fully developed boiling regime deteriorates with increased flow rate due to the increase in pumping power flux.

  13. Calculation of Water Supply to Hydraulic Jet Devices

    Directory of Open Access Journals (Sweden)

    M. V. Krautsou

    2006-01-01

    Full Text Available Dependence for calculation of working fluid supply to water-air ejector is proposed. The de­pendence has been derived via analysis and processing of data being obtained by experimental research of water-jet devices.

  14. Hydraulic fluids and jet engine oil: pyrolysis and aircraft air quality.

    Science.gov (United States)

    van Netten, C; Leung, V

    2001-01-01

    Incidents of smoke in aircraft cabins often result from jet engine oil and/or hydraulic fluid that leaks into ventilation air, which can be subjected to temperatures that exceed 500 degrees C. Exposed flight-crew members have reported symptoms, including dizziness, nausea, disorientation, blurred vision, and tingling in the legs and arms. In this study, the authors investigated pyrolysis products of one jet engine oil and two hydraulic fluids at 525 degrees C. Engine oil was an important source of carbon monoxide. Volatile agents and organophosphate constituents were released from all the agents tested; however, the neurotoxin trimethyl propane phosphate was not found. The authors hypothesized that localized condensation of pyrolysis products in ventilation ducts, followed by mobilization when cabin heat demand was high, accounted for mid-flight incidents. The authors recommended that carbon monoxide data be logged continuously to capture levels during future incidents.

  15. Hydraulics.

    Science.gov (United States)

    Decker, Robert L.; Kirby, Klane

    This curriculum guide contains a course in hydraulics to train entry-level workers for automotive mechanics and other fields that utilize hydraulics. The module contains 14 instructional units that cover the following topics: (1) introduction to hydraulics; (2) fundamentals of hydraulics; (3) reservoirs; (4) lines, fittings, and couplers; (5)…

  16. Water-Air Mixing Jet Produced by Electro-hydraulic Impulse Technology Strengthening the Quality of Surface of Metal Materials

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Electro-hydraulic impulse water-air mixing jet by which the quality of metal materials can be improved is described in this paper. The experimental results proved that the hardness and the micro-hardness of the surface layer of metal materials can be improved with this method, for example, the microhardness of CrWMn can be increased by 35.62percent.

  17. Analogy Between Hydraulic Jump in Films Formed by Impinging Liquid Jet and Critical Flow in Internal Flows

    Institute of Scientific and Technical Information of China (English)

    Jaroslaw Mikielewicz

    2003-01-01

    Formulated are simple models for the flow in liquid film, formed by impinging jet, and a two-phase downward flow in pipe. The models are based on simplified equations of mass, momentum and energy. The solutions of such conservation equations may have regular points belonging to one integral curve only as well as turning points can be found amongst them, which refer to extreme values in the appropriate co-ordinate system. The solutions can also have singular points belonging to none or more than one integral curve. Both the turning and singular points have a clear physical meaning. They could be linked to critical flow conditions in the pipe flow or to the so-called hydraulic jump. Analogy existing between critical conditions in the pipe and the flow of liquid films formed by the liquid jet have been shown in the paper.

  18. Operation history of hydraulic jet pump on teh Chengbei oil field, China. Chengbei yuden ni okeru haidororikku jet pump no shiyo jisseki

    Energy Technology Data Exchange (ETDEWEB)

    Terao, Yoshihiro; Takagi, Sunao

    1989-11-01

    Changbei oil field in China uses hydraulic jet pump(HJP) to cope with the increase of oil production and increase of water content in the oil field. This paper described the practical result. This pump makes high speed jet by driving fluid, and converts the dynamic energy to pressure energy by decelerating with a diffuser to push up oil. Wellheads damaged by sand friction or near the gas cap were removed. The production from March, 1988 to October increased at the rate of 114kl/day at total 8 wellheads. Heavy oil of API specific gravity of 16 degree could be proved. Since the separation of oil and water was inferior, so that the countermeasures were studied but the cause was not known. Troubles or failures of main body, nozzle and throat of HJP were not occurred. Any effect could not be found at a wellhead of water content exceeding 50 to 60% because only water production increased. Consequently, this process could result the increase of oil production with lower cost and without mechanical failures. 2 refs., 7 figs., 7 tabs.

  19. Model of Loosen Blasting Assisted by High-Pressure Water Jet Spiral-Notch%高压水射流螺旋式切槽辅助松动爆破模型

    Institute of Scientific and Technical Information of China (English)

    粟登峰; 康勇; 王晓川; 郑丹丹

    2016-01-01

    A new technology of loosen blasting assisted by high-pressure water jet spiral-notch was put forward based on its unique advantages of water jet cutting, and the geometric model for water jet notched boreholes was established based on experiments. Furthermore, by employing fracture mechanics and Westergaard stress function method, the functions of complex variables was confirmed, and the stress field acted upon the spirally water jet notching borehole by quasi-static explosion gas was derived. The stress intensity factor of spiral-notch boreholes with high-pressure water jet was determined, and the loosening effect of loosen blasting assisted by high-pressure water jet spiral-notch was also analyzed. Finally, ANSYS/LS-DYNA was applied to verify the theoretical model, and the results of the numerical simulation are almost comparable to the model.%基于水射流独特的切割优势提出了高压水射流螺旋式切槽辅助松动爆破的新方法,实验研究了高压水射流切割煤岩体所形成缝槽的断口形貌并建立了其几何模型。在此基础上,基于断裂力学理论同时结合Westergaard方法,确定了复变函数,进而推导出爆生气体准静态作用下射流螺旋切槽孔的应力场公式,得到了射流螺旋切槽孔缝槽尖端应力强度因子计算公式,并分析了高压水射流切槽辅助松动爆破松动效应。最后,采用ANSYS/LS-DYNA数值模拟软件对该模型进行了验证,结果符合较好。

  20. Stomaching Notch

    Science.gov (United States)

    Yin, Xiaolei; Karp, Jeffrey M

    2015-01-01

    The self-renewal and differentiation of tissue stem cells must be tightly controlled. Unrestrained self-renewal leads to over-proliferation of stem cells, which may cause tumor formation, while uncontrolled differentiation leads to depletion of the stem cell pool. In this issue of The EMBO Journal, Demitrack et al (2015) show that the Notch pathway is a key regulator of Lgr5 antral stem cell self-renewal and differentiation. Notch signaling controls the proliferation and differentiation of stem cells as well as gastric tissue growth, while uncontrolled Notch activity in stem cells leads to polyp formation. PMID:26358838

  1. Planetary-scale hydraulic jumps and transonic jet-streaks in the MACDA reanalysis of the Martian atmosphere: a comparison with Earth's lower mesosphere

    Science.gov (United States)

    Dowling, Timothy E.; Bradley, Mary Elizabeth; Lewis, Stephen R.; Read, Peter L.

    2016-10-01

    We have analyzed the Mars MACDA V1.0 global reanalysis on potential-temperature surfaces, θ, over the range θ = 400 to 900 K (~30 to ~60 km). The strongest seasonal wind, the northern-winter polar jet, exhibits two intriguing features: i) transonic jet streaks and ii) the juxtaposition of regions of shooting and tranquil flow, in the sense of Froude-number hydraulics, which suggests a planetary-scale hydraulic jump. Mesoscale bores have been studied on Mars, but to our knowledge the above two features have not been reported elsewhere. To characterize the basic state, we examine scatter plots of Ertel potential vorticity, Q, versus Bernoulli streamfunction, B, and fit the linear model Q/Q0 = 1 - μ0 (B-B0). In autumn, winter and spring, the nondimensionalized correlation parameter, μ'0 = (NH)2 μ0, in mid-latitudes is positive and nearly constant in time. Its value is close to unity at the bottom of the study region and gradually decreases with increasing θ (increasing altitude). In northern summer it swings negative. These attributes match Earth's lower mesosphere (θ = 2000 to 3000 K; ~48 to ~62 km). In southern summer, Ls ~ 270○, a hypsometric flaring of the θ layers, which is not seen in northern summer, is associated with the previously reported reduction of Q to approximately zero across the entire southern hemisphere and northern tropics. Between each winter polar jet and pole, especially in the north, there is a large spread of Q over a small domain of B, which is unlike Earth and may be related to the aforementioned hydraulic jump. We are currently examining 3D Lagrangian fluid trajectories to better characterize the rotating hydraulics of the system as a function of season.

  2. Notch Antennas

    Science.gov (United States)

    Lee, Richard Q.

    2004-01-01

    Notch antennas, also known as the tapered slot antenna (TSA), have been the topics of research for decades. TSA has demonstrated multi-octave bandwidth, moderate gain (7 to 10 dB), and symmetric E- and H- plane beam patterns and can be used for many different applications. This chapter summarizes the research activities on notch antennas over the past decade with emphasis on their most recent advances and applications. This chapter begins with some discussions on the designs of single TSA; then follows with detailed discussions of issues associated with TSA designs and performance characteristics. To conclude the chapter, some recent developments in TSA arrays and their applications are highlighted.

  3. Outburst Prevention Technology with Borehole Hydraulic Jet Through Strata in Floor Gateway%底板巷穿层钻孔水力冲孔防突技术

    Institute of Scientific and Technical Information of China (English)

    刘明举; 郭献林; 李波; 王冕

    2011-01-01

    针对新安矿14211运输巷掘进过程中面临的煤与瓦斯突出问题,为了研究和确定适合新安煤田三软煤层赋存特点的水力冲孔工艺和消突评价体系,使其快速消除工作面突出危险性,提高煤巷掘进速度,采用底板巷穿层钻孔水力冲孔防突措施,按照考察出的冲孔影响半径均匀布置钻孔,排出部分煤体和瓦斯,使煤体卸压增透.试验结果表明,底板巷穿层水力冲孔技术较好地适应和利用了三软煤层的赋存特点,消除了工作面的突出危险性,掘进速度也由之前的40 m/月提高到75m/月,提高了87.5%.%According to coal and gas outburst problems occurred in the heading process of the No.14211 transportation gateway in Xin'an Mine, in order to study and set up the borehole hydraulic jet technique and the outburst evaluation system suitable for the three soft seam deposit features in Xin'an Coalfield, to rapidly eliminate the outburst danger of the heading face and to improve the seam gateway heading speed, the outburst prevention measures with borehole hydraulic jet through the strata in the floor gateway were applied.According the investigation of the borehole hydraulic jet influence radius, a layout of the berehole pattern was evenly set up and a partial coal and gas could be discharged.Thus the seam pressure could be released and the permeability of the seam could be improved.The experiment result showed that the borehole hydraulic jet technology passed through strata in the floor gateway would be well suitable for and utilization of the deposit features of the three soft seam and could eliminate the outburst danger of the heading face.Thus the heading speed could be improved from the previous 40 m/month to 75 m/month and the heading efficiency was improved by 87.5%.

  4. Numerical Simulation of Working Parameters for Hydraulic Oscillator Jet%射流式水力振荡器工作参数数值模拟

    Institute of Scientific and Technical Information of China (English)

    那枫

    2016-01-01

    通过 CFD 数值模拟方法分析射流式水力振荡器内部复杂流场,尤其在射流式压力脉冲短节内部由射流元件、缸体、活塞、节流盘所组成的复杂流场的速度场、压力场变化情况。运用 Solid-works、Hypermesh、FLUENT 软件,建立合理模型,选择合理的数值计算方法,进行了射流式水力振荡器内部流场数值模拟研究,对优化该工具的结构设计具有指导性意义。%By CFD numerical simulation method,complex flow field inside the Jet hydrodynamic oscillators is analyzed,especially within the pressure pulse jet nipple by Jet components,cylin-ders,pistons,throttle plate consisting of complex flow field velocity,pressure changes.Using Solidworks,Hypermesh,FLUENT software are used to establish a rational model,reasonable se-lection of numerical methods and select reasonable numerical simulation to study jet flow field in hydraulic oscillator for optimization of structural design of the tool,which are of guiding signifi-cance.

  5. Notch filter

    Science.gov (United States)

    Shelton, G. B. (Inventor)

    1977-01-01

    A notch filter for the selective attenuation of a narrow band of frequencies out of a larger band was developed. A helical resonator is connected to an input circuit and an output circuit through discrete and equal capacitors, and a resistor is connected between the input and the output circuits.

  6. Thermo - hydraulic analysis of a cryogenic jet: application to helium recovery following resistive transitions in the LHC

    CERN Document Server

    Chorowski, M; Konopka, G

    1999-01-01

    A resistive transition (quench) of the LHC sector magnets will be followed by cold helium venting to a quench buffer volume of 2000 m3 at ambient temperature. The volume will be composed of eight medium-pressure (2 MPa) gas storage tanks made of carbon steel, which constrains the temperature of the wall to be higher than -50 oC (223 K). Possible spot cooling intensity and thermo-mechanical stresses in the tank wall following helium injection have been analysed previously and the aim of the present study is experimental verification of basic assumptions concerning cryogenic jet parameters and heat transfer between jet crown and tank wall. For this purpose jet diameter, velocity profile and convective heat transfer between jet and steel plate have been measured. A simple jet model description based on momentum conservation has been proposed. Then, the lowest possible temperature of the tank wall which may occur has been assessed.

  7. Multi-elemental analysis of jet engine lubricating oils and hydraulic fluids and their implication in aircraft air quality incidents.

    Science.gov (United States)

    van Netten, C

    1999-05-07

    The flight crews of aircraft often report symptoms including dizziness, nausea, disorientation, blurred vision and tingling in legs and arms. Many of these incidents have been traced to contamination of cabin air with lubricating oil, as well as hydraulic fluid, constituents. Considering that these air contaminants are often subjected to temperatures in excess of 500 degrees C, a large number of different exposures can be expected. Although the reported symptoms are most consistent with exposures to volatile organic compounds, carbon monoxide, and the organophosphate constituents in these oils and fluids, the involvement of these agents has not been clearly demonstrated. Possible exposure to toxic elements, such as lead, mercury, thallium and others, have not been ruled out. In order to assess the potential of exposure to toxic elements a multi-elemental analysis was done on two hydraulic fluids and three lubricating oils which have been implicated in a number of air quality incidents. A secondary objective was to establish if the multi-elemental concentrations of the fluids tested are different enough to allow such an analysis to be used as a possible method of identifying the source of exposure that might have been present during aircraft air quality incidents. No significant concentrations of toxic elements were identified in any of the oils or hydraulic fluids. The elemental compositions of the samples were different enough to be used for identification purposes and the measurement of only three elements was able to achieve this. Whether these findings have an application, in aircraft air quality incident investigations, needs to be established with further studies.

  8. The Applications of Dry Jet Mixing in the Coastal Areas of Hydraulic Engineering%粉喷桩在沿海地区水利工程中的的应用

    Institute of Scientific and Technical Information of China (English)

    戴恩运

    2013-01-01

      在沿海地区水利工程中,水泥粉喷搅拌桩是地基与基础处理常用的一种方法。本文通过作者的工作实践,并结合工程实例对粉喷桩在沿海地区水利工程中的应用进行简单的阐述与分析。%In the coastal areas of hydraulic engineering, the c-ement powder jet mixing pile is a common method of the sub-grade and the basis of processing. In this article, the author ba-ses on the working practices, briefly elaborates and analysis th-e applications of Dry Jet Mixing in the coastal areas of hydrau-lic engineering.

  9. Notch Inhibitors for Cancer Treatment

    OpenAIRE

    Espinoza, Ingrid; Miele, Lucio

    2013-01-01

    Notch signaling is an evolutionarily conserved cell signaling pathway involved in cell fate during development, stem cell renewal and differentiation in postnatal tissues. Roles for Notch in carcinogenesis, in the biology of cancer stem cells and tumor angiogenesis have been reported. These features identify Notch as a potential therapeutic target in oncology. Based on the molecular structure of Notch receptor, Notch ligands and Notch activators, a set of Notch pathway inhibitors have been de...

  10. Waveform frequency notching

    Energy Technology Data Exchange (ETDEWEB)

    Doerry, Armin W.; Andrews, John

    2017-05-09

    The various technologies presented herein relate to incorporating one or more notches into a radar spectrum, whereby the notches relate to one or more frequencies for which no radar transmission is to occur. An instantaneous frequency is monitored and if the frequency is determined to be of a restricted frequency, then a radar signal can be modified. Modification can include replacing the signal with a signal having a different instantaneous amplitude, a different instantaneous phase, etc. The modification can occur in a WFS prior to a DAC, as well as prior to a sin ROM component and/or a cos ROM component. Further, the notch can be dithered to enable formation of a deep notch. The notch can also undergo signal transitioning to enable formation of a deep notch. The restricted frequencies can be stored in a LUT against which an instantaneous frequency can be compared.

  11. Experimental and Analysis for Self-excited Pressure Oscillations and Noise of Hydraulic Jet Pipe Servo-valve%液压射流管伺服阀自激振荡和噪声实验与分析

    Institute of Scientific and Technical Information of China (English)

    邹贤珍

    2016-01-01

    在液压流场中,液压伺服阀的高频噪声主要来自于自身的震荡。采用压电式动态压力传感器和扩音器对液压射流管伺服阀的自激振荡和噪声进行检测。试验中,将伺服阀的进口压力控制在11~21 MPa。为了将实验数据精准化,利用FFT和小波分析法对压力震荡信号和噪声信号进行处理。根据分析结果找出自激振荡和噪声产生的原因,并为降低液压伺服阀的自激振荡和噪声提供了方法。%In the hydraulic flow field, the high frequency noise of the hydraulic servo-valve is mainly derived from its own shock. Using the piezoelectric dynamic pressure sensor and amplifier, hydraulic jet pipe servo-valve self-excited vibration and noise were de-tected.In the test, the inlet pressure of the servo-valve was controlled in 11~21 MPa.In order to make the experimental data accurate, FFT and wavelet analysis method were used to deal with the pressure oscillation signal and noise signal.According to the analysis re-sults, the causes of the self-excited oscillation and noise were found out.It provides method for reducing vibration and noise of hydrau-lic servo-valve.

  12. Kick it up a notch: Notch signaling and kidney fibrosis

    OpenAIRE

    2014-01-01

    Notch is a critical regulator of kidney development, but the pathway is mostly silenced once kidney maturation is achieved. Recent reports demonstrated increased expression of Notch receptors and ligands both in acute and chronic kidney injury. In vivo studies indicated that Notch activation might contribute to regeneration after acute kidney injury; on the other hand, sustained Notch expression is causally associated with interstitial fibrosis and glomerulosclerosis. This review will summari...

  13. Notch Signaling in Pancreatic Development

    OpenAIRE

    2015-01-01

    The Notch signaling pathway plays a significant role in embryonic cell fate determination and adult tissue homeostasis. Various studies have demonstrated the deep involvement of Notch signaling in the development of the pancreas and the lateral inhibition of Notch signaling in pancreatic progenitor differentiation and maintenance. The targeted inactivation of the Notch pathway components promotes premature differentiation of the endocrine pancreas. However, there is still the contrary opinion...

  14. Stress concentration at notches

    CERN Document Server

    Savruk, Mykhaylo P

    2017-01-01

    This book compiles solutions of linear theory of elasticity problems for isotropic and anisotropic bodies with sharp and rounded notches. It contains an overview of established and recent achievements, and presents the authors’ original solutions in the field considered with extensive discussion. The volume demonstrates through numerous, useful examples the effectiveness of singular integral equations for obtaining exact solutions of boundary problems of the theory of elasticity for bodies with cracks and notches. Incorporating analytical and numerical solutions of the problems of stress concentrations in solid bodies with crack-like defects, this volume is ideal for scientists and PhD students dealing with the problems of theory of elasticity and fracture mechanics. Stands as a modern and extensive compendium of solutions to the problems of linear theory of elasticity of isotropic and anisotropic bodies with sharp and rounded notches; Adopts a highly reader-friendly layout of tables, charts, approximation ...

  15. Advanced Performance Hydraulic Wind Energy

    Science.gov (United States)

    Jones, Jack A.; Bruce, Allan; Lam, Adrienne S.

    2013-01-01

    The Jet Propulsion Laboratory, California Institute of Technology, has developed a novel advanced hydraulic wind energy design, which has up to 23% performance improvement over conventional wind turbine and conventional hydraulic wind energy systems with 5 m/sec winds. It also has significant cost advantages with levelized costs equal to coal (after carbon tax rebate). The design is equally applicable to tidal energy systems and has passed preliminary laboratory proof-of-performance tests, as funded by the Department of Energy.

  16. Comparative Notched Box Plots.

    Science.gov (United States)

    1983-06-01

    provides a 95.1% confidence interval. See Noether (1976, Table E). Furthermore, this notch is not necessarily sym- metric about the sample median as in...distribution of the sign test). ( Noether 1976, Chapter 12; Lehmann 1975, Chapter 4; Hollander and Wolfe 1972, Chapter 3.) Thus, exact rather than approximate...binomial with parameters n and .5, i.e., b(n, .5). We will refer to dx as the notch depth. Noether (1978, Table E) provides the d. values; otherwise, they

  17. Fatigue life estimation for different notched specimens based on the volumetric approach

    Directory of Open Access Journals (Sweden)

    Esmaeili F.

    2010-06-01

    Full Text Available In this paper, the effects of notch radius for different notched specimens has been studied on the values of stress concentration factor, notch strength reduction factor, and fatigue life duration of the specimens. The material which has been selected for this investigation is Al 2024T3 . Volumetric approach has been applied to obtain the values of notch strength reduction factor and results have been compared with those obtained from the Neuber and Peterson methods. Load controlled fatigue tests of mentioned specimens have been conducted on the 250kN servo-hydraulic Zwick/Amsler fatigue testing machine with the frequency of 10Hz. The fatigue lives of the specimens have also been predicted based on the available smooth S-N curve of Al2024-T3 and also the amounts of notch strength reduction factor which have been obtained from volumetric, Neuber and Peterson methods. The values of stress and strain around the notch roots are required to predict the fatigue life of notched specimens, so Ansys finite element code has been used and non-linear analyses have been performed to obtain the stress and strain distributions around the notches. The plastic deformations of the material have been simulated using multi-linear kinematic hardening and cyclic stress-strain relation. The work here shows that the volumetric approach does a very good job for predicting the fatigue life of the notched specimens.

  18. Electrochemical polishing of notches

    Science.gov (United States)

    Kephart, Alan R.; Alberts, Alfred H.

    1989-01-01

    An apparatus and method are disclosed for the selective electrochemical polishing of a lateral tip of a deep longitudinal notch in a work piece used to test crack initiation properties of materials. A DC power source is connected to the work piece and to an electrode disposed laterally along the distal end of an insulated body which is inserted in the longitudinal notch. The electrode and distal end of the body are disposed along the tip of the notch, but are spaced from the notch so as to provide a lateral passage for an electrolyte. The electrolyte is circulated through the passage so that the electrolyte only contacts the work piece adjacent the passage. Conveniently, the electrolyte is circulated by use of an inlet tube and an outlet tube provided at opposite ends of the passage. These tubes are preferably detachably located adjacent the ends of the passage and suitable seals are provided. A holding device including arms to which the tubes are attached is conveniently used to rapidly and easily locate the test specimen with the passage aligned with the tubes. The electrode is preferably a wire which is located in grooves along the distal end of the insulated body and up one side of the body or a plastic sheath insulated thin metal strip.

  19. Notch strength of composites

    Science.gov (United States)

    Whitney, J. M.

    1983-01-01

    The notch strength of composites is discussed. The point stress and average stress criteria relate the notched strength of a laminate to the average strength of a relatively long tensile coupon. Tests of notched specimens in which microstrain gages have been placed at or near the edges of the holes have measured strains much larger that those measured in an unnotched tensile coupon. Orthotropic stress concentration analyses of failed notched laminates have also indicated that failure occurred at strains much larger than those experienced on tensile coupons with normal gage lengths. This suggests that the high strains at the edge of a hole can be related to the very short length of fiber subjected to these strains. Lockheed has attempted to correlate a series of tests of several laminates with holes ranging from 0.19 to 0.50 in. Although the average stress criterion correlated well with test results for hole sizes equal to or greater than 0.50 in., it over-estimated the laminate strength in the range of hole sizes from 0.19 to 0.38 in. It thus appears that a theory is needed that is based on the mechanics of failure and is more generally applicable to the range of hole sizes and the varieties of laminates found in aircraft construction.

  20. Scaling approach and thermal-hydraulic analysis in the reactor cavity cooling system of a high temperature gas -cooled reactor and thermal-jet mixing in a sodium fast reactor

    Science.gov (United States)

    Omotowa, Olumuyiwa A.

    This dissertation develops and demonstrates the application of the top-down and bottom-up scaling methodologies to thermal-hydraulic flows in the reactor cavity cooling system (RCCS) of the high temperature gas reactor (HTGR) and upper plenum of the sodium fast reactor (SFR), respectively. The need to integrate scaled separate effects and integral tests was identified. Experimental studies and computational tools (CFD) have been integrated to guide the engineering design, analysis and assessment of this scaling methods under single and two-phase flow conditions. To test this methods, two applicable case studies are considered, and original contributions are noted. Case 1: "Experimental Study of RCCS for the HTGR". Contributions include validation of scaling analysis using the top-down approach as guide to a ¼-scale integral test facility. System code, RELAP5, was developed based on the derived scaling parameters. Tests performed included system sensitivity to decay heat load and heat sink inventory variations. System behavior under steady-state and transient scenarios were predicted. Results show that the system has the capacity to protect the cavity walls from over-heating during normal operations and provide a means for decay heat removal under accident scenarios. A full width half maximum statistical method was devised to characterize the thermal-hydraulics of the non-linear two-phase oscillatory behavior. This facilitated understanding of the thermal hydraulic coupling of the loop segments of the RCCS, the heat transfer, and the two-phase flashing flow phenomena; thus the impact of scaling overall. Case 2: "Computational Studies of Thermal Jet Mixing in SFR". In the pool-type SFR, susceptible regions to thermal striping are the upper instrumentation structure and the intermediate heat exchanger (IHX). We investigated the thermal mixing above the core to UIS and the potential impact due to poor mixing. The thermal mixing of dual-jet flows at different

  1. 一种多层长井段油水井解堵水力喷射棒的研制%Development of a Kind of Hydraulic Jet Bar for Multilayer Long Interval Oil-water Well Plug Removal

    Institute of Scientific and Technical Information of China (English)

    杜勇; 李军; 刘江涛; 滕学伟; 宾永锋

    2012-01-01

    由于常规水射流工具存在处理范围小、重复起下管柱作业等问题,使其在多层长井段油水井中应用效果较差,一定程度上影响了处理效果。为此,研制了一种适用于多层长井段油水井解堵水力喷射棒。该喷射棒在其底部安装了喷嘴,围绕喷头本体螺旋设置喷嘴,扩大了处理范围。它可根据不同井段长度的需要来设计喷头本体的长度,螺旋设置各种喷嘴,使其用于较短井段时,其水力冲击更均匀,效果更好,可实现对地层的综合处理。现场应用结果表明,该喷射棒与常规工具相比,提高了处理范围,且处理效果好;有效解决了长井段均匀酸化问题,为油水井解除近井污染、实现增产增注提供了技术支持。%The small treatment scope of conventional water jet tool and repeated trip runs give rise to its poor application effect in multilayer long interval oil-water well. This affects the effect of treatment in some degree. Therefore, a type of hydraulic jet bar suitable for muhilayer long interval oil-water well plug removal was developed. The nozzle was installed on the bottom of the bar and it was set up helically around the nozzle body, thus enlarging the scope of treatment. The length of the nozzle body can be designed according to the requirement of dif- ferent well interval lengths, and various nozzles can be set up helically. When it is applied to relatively short inter- vals, the hydraulic impact is more even with a better effect. The comprehensive treatment of formation can be a- chieved. The field application shows that compared with conventional tools, the jet bar has improved the scope of treatment with a better effect. The acidization problem of long intervals has been solved effectively, providing the technological support for eliminating near wellbore pollution in oil-water well and achieving yield and injection increase.

  2. Notch in Pathological Angiogenesis and Lymphangiogenesis

    Science.gov (United States)

    2012-05-01

    endothelial cells ( HUVEC ). Notch family receptors and ligands (Notch 1, Notch 4, Dll-4, Jag1) are present in HUVEC . Activation of Notch in HUVEC inhibits...associated gene, which is also repressed in HUVEC upon Notch activation) (data not shown). Figure 2a

  3. Hydraulic structures

    CERN Document Server

    Chen, Sheng-Hong

    2015-01-01

    This book discusses in detail the planning, design, construction and management of hydraulic structures, covering dams, spillways, tunnels, cut slopes, sluices, water intake and measuring works, ship locks and lifts, as well as fish ways. Particular attention is paid to considerations concerning the environment, hydrology, geology and materials etc. in the planning and design of hydraulic projects. It also considers the type selection, profile configuration, stress/stability calibration and engineering countermeasures, flood releasing arrangements and scouring protection, operation and maintenance etc. for a variety of specific hydraulic structures. The book is primarily intended for engineers, undergraduate and graduate students in the field of civil and hydraulic engineering who are faced with the challenges of extending our understanding of hydraulic structures ranging from traditional to groundbreaking, as well as designing, constructing and managing safe, durable hydraulic structures that are economical ...

  4. HYDRAULIC SERVO

    Science.gov (United States)

    Wiegand, D.E.

    1962-05-01

    A hydraulic servo is designed in which a small pressure difference produced at two orifices by an electrically operated flapper arm in a constantly flowing hydraulic loop is hydraulically amplified by two constant flow pumps, two additional orifices, and three unconnected ball pistons. Two of the pistons are of one size and operate against the additional orifices, and the third piston is of a different size and operates between and against the first two pistons. (AEC)

  5. Application of hydraulic pulse cavitating jet technology in unconventional well drilling%水力脉冲空化射流技术在非常规钻井中的应用

    Institute of Scientific and Technical Information of China (English)

    辛建华

    2012-01-01

    For some unconventional wells, due to old stratum and poor drillability, it takes longer drilling period and encounters more complex situation, including obvious decline of mechanical drilling rate and soaring drilling cost. Based on the drilling prac-tice of unconventional wells, it is found that conventional drilling technique cannot slove the problems of low mechanical drilling rate and long drilling period. Through research, oil experts found that, under the conditions of fixed hydraulic parameters, the use of pulse jet and cavitating jet could have a greater impact load, improve the efficiency of rock clearing and rock breaking, and success-fully resolve the problem of low mechanical drilling rate and long drilling period. By tracking and comparative analysis of the appli-cation of hydraulic pulse cavitating jet technology in the drilling of unconventional wells, this paper researched on the feasibility of enhancing mechanical drilling rate by the technology and explored the means to improve the tools structure of the technology, hy-draulic parameters, drilling tools combination and the adaptability of the technology to stratum. All the researches above were of practical meanings in making technical preparation for the improvement of mechanical drilling rate of unconventional wells.%部分非常规井由于地层古老,岩性致密,可钻性差,钻井周期长,钻井过程中遇到的复杂情况增多,机械钻速下降幅度明显增大,同时钻井成本也急剧增加。从非常规钻井施工实际不难发现,采用传统钻井工艺和方式不能解决钻井机械钻速低,钻井周期长等难题。目前,石油专家通过探索研究发现,在水力参数不变的条件下,利用脉冲射流和空化射流能够产生较大的冲击载荷,提高清岩和破岩效率,从而顺利解决了钻井机械钻速低,钻井周期长等难题。通过跟踪、对比分析水力空化射流钻井技术在非常规钻井中的应

  6. NOTCH FILTER USING SIMULATED INDUCTOR

    Directory of Open Access Journals (Sweden)

    D.SUSAN,

    2011-06-01

    Full Text Available The design of analog filters at low frequencies is not possible because the size of inductors becomes very large. In such cases, the simulated inductors using operational amplifiers are used. This paper deals with the implementation of notch filter using band pass filter which uses simulated inductor where the direct implementation of notch filter using simulated inductor is not possible because of floating inductor. The design of notch filter and the simulation done in PSPICE is presented.

  7. Notch Charge-Coupled Devices

    Science.gov (United States)

    Janesick, James

    1992-01-01

    Notch charge-coupled devices are imaging arrays of photodetectors designed to exhibit high charge-transfer efficiencies necessary for operation in ultra-large array, and less vulnerable to degradation by energetic protons, neutrons, and electrons. Main channel of horizontal register includes deep narrow inner channel (notch). Small packets of charge remain confined to notch. Larger packets spill into rest of channel; transferred in usual way. Degradation of charge-transfer efficiency by energetic particles reduced.

  8. Ubiquitination of Notch1 is regulated by MAML1-mediated p300 acetylation of Notch1

    Energy Technology Data Exchange (ETDEWEB)

    Popko-Scibor, Anita E.; Lindberg, Mikael J.; Hansson, Magnus L.; Holmlund, Teresa [Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm (Sweden); Wallberg, Annika E., E-mail: Annika.Wallberg@ki.se [Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm (Sweden)

    2011-12-16

    Highlights: Black-Right-Pointing-Pointer p300 acetylates conserved lysines within Notch1 C-terminal nuclear localization signal. Black-Right-Pointing-Pointer MAML1 and CSL, components of Notch transcription complex, increase Notch acetylation. Black-Right-Pointing-Pointer MAML1-dependent acetylation of Notch1 by p300 decreases the ubiquitination of Notch1. Black-Right-Pointing-Pointer CDK8 inhibits Notch acetylation and Notch transcription enhanced by p300. -- Abstract: Earlier studies demonstrated the involvement of the p300 histone acetyltransferase in Notch signaling but the precise mechanisms by which p300 might modulate Notch function remains to be investigated. In this study, we show that p300 acetylates Notch1 ICD in cell culture assay and in vitro, and conserved lysines located within the Notch C-terminal nuclear localization signal are essential for Notch acetylation. MAML1 and CSL, which are components of the Notch transcription complex, enhance Notch acetylation and we suggest that MAML1 increases Notch acetylation by potentiating p300 autoacetylation. Furthermore, MAML1-dependent acetylation of Notch1 ICD by p300 decreases the ubiquitination of Notch1 ICD in cellular assays. CDK8 has been shown to target Notch1 for ubiquitination and proteosomal degradation. We show that CDK8 inhibits Notch acetylation and Notch transcription enhanced by p300. Therefore, we speculate that acetylation of Notch1 might be a mechanism to regulate Notch activity by interfering with ubiquitin-dependent pathways.

  9. Hydraulic mining method

    Science.gov (United States)

    Huffman, Lester H.; Knoke, Gerald S.

    1985-08-20

    A method of hydraulically mining an underground pitched mineral vein comprising drilling a vertical borehole through the earth's lithosphere into the vein and drilling a slant borehole along the footwall of the vein to intersect the vertical borehole. Material is removed from the mineral vein by directing a high pressure water jet thereagainst. The resulting slurry of mineral fragments and water flows along the slant borehole into the lower end of the vertical borehole from where it is pumped upwardly through the vertical borehole to the surface.

  10. Spinning hydraulic jump

    Science.gov (United States)

    Abderrahmane, Hamid; Kasimov, Aslan

    2013-11-01

    We report an experimental observation of a new symmetry breaking of circular hydraulic jump into a self-organized structure that consists of a spinning polygonal jump and logarithmic-spiral waves of fluid elevation downstream. The waves are strikingly similar to spiral density waves in galaxies. The fluid flow exhibits counterparts of salient morphological features of galactic flows, in particular the outflow from the center, jets, circum-nuclear rings, gas inflows toward the galactic center, and vortices. The hydrodynamic instability revealed here may have a counterpart that plays a role in the formation and sustainability of spiral arms in galaxies.

  11. Notch as a tumour suppressor.

    Science.gov (United States)

    Nowell, Craig S; Radtke, Freddy

    2017-03-01

    The Notch signalling cascade is an evolutionarily conserved pathway that has a crucial role in regulating development and homeostasis in various tissues. The cellular processes and events that it controls are diverse, and continued investigation over recent decades has revealed how the role of Notch signalling is multifaceted and highly context dependent. Consistent with the far-reaching impact that Notch has on development and homeostasis, aberrant activity of the pathway is also linked to the initiation and progression of several malignancies, and Notch can in fact be either oncogenic or tumour suppressive depending on the tissue and cellular context. The Notch pathway therefore represents an important target for therapeutic agents designed to treat many types of cancer. In this Review, we focus on the latest developments relating specifically to the tumour-suppressor activity of Notch signalling and discuss the potential mechanisms by which Notch can inhibit carcinogenesis in various tissues. Potential therapeutic strategies aimed at restoring or augmenting Notch-mediated tumour suppression will also be highlighted.

  12. Notch Signaling in Neuroendocrine Tumors

    Directory of Open Access Journals (Sweden)

    Judy Sue Crabtree

    2016-04-01

    Full Text Available Carcinoids and neuroendocrine tumors (NETs are a heterogeneous group of tumors that arise from the neuroendocrine cells of the GI tract, endocrine pancreas and the respiratory system. NETs remain significantly understudied with respect to molecular mechanisms of pathogenesis, particularly the role of cell fate signaling systems like Notch. The abundance of literature on the Notch pathway is a testament to its complexity in different cellular environments. Notch receptors can function as oncogenes in some contexts, and tumor suppressors in others. The genetic heterogeneity of NETs suggests that to fully understand the roles and the potential therapeutic implications of Notch signaling in NETs, a comprehensive analysis of Notch expression patterns and potential roles across all NET subtypes is required.

  13. Basic hydraulics

    CERN Document Server

    Smith, P D

    1982-01-01

    BASIC Hydraulics aims to help students both to become proficient in the BASIC programming language by actually using the language in an important field of engineering and to use computing as a means of mastering the subject of hydraulics. The book begins with a summary of the technique of computing in BASIC together with comments and listing of the main commands and statements. Subsequent chapters introduce the fundamental concepts and appropriate governing equations. Topics covered include principles of fluid mechanics; flow in pipes, pipe networks and open channels; hydraulic machinery;

  14. Mechanical Analysis and Field Application of Coiled Tubing Hydraulic Jet Fracturing String%连续管水力喷射压裂管柱力学分析及现场应用

    Institute of Scientific and Technical Information of China (English)

    王鹏; 王思淇; 张倩

    2016-01-01

    To address the stability issue of coiled tubing operation, the stress and elongation of two kinds of hy⁃draulic jet annulus sand delivery fracturing string have been analyzed in the whole process of operation in Daqing oil⁃field�The main research include: (1) Stress and deformation analysis of the coiled tubing hydraulic jet fracturing string in the whole operation, and the corresponding mathematical model; (2) Analysis on the two common packer K344 and Y211 during fracturing; processing methods of the boundary conditions at the bottom of the fracturing string during the setting of different packers; (3) Calculation of the deformation and stress of the coiled tubing fracturing string during fracturing operation of Well Gulongnan P , and comparison with the field measured data�Analysis results showed that the mechanical model results have a small deviation with the measured data�The research results could provide theoretical guidance for coiled tubing hydraulic jet fracturing operation design and construction.%连续管水力喷射压裂技术结合了水力喷射射孔定点压裂的优越性与连续管的拖动灵活性,极大地提高了水力喷射压裂作业的工作效率。为解决该技术存在的连续管作业稳定性较差的问题,以大庆油田2种水力喷射环空加砂压裂工艺管柱为例,对管柱进行了全作业过程受力分析及伸长量分析,主要包括:(1)分析管柱全作业过程受力及变形,并给出了相应的计算模型;(2)分析K344和Y2112种常用封隔器压裂作业工况,给出了不同封隔器坐封时压裂管柱底部边界条件处理方法;(3)实例计算分析古龙南P井连续管压裂作业时管柱受力变形,并与现场实测数据进行了对比分析。分析结果表明:力学计算模型计算结果与现场实测数据偏差较小。研究成果能够为连续管水力喷射压裂作业设计施工提供理论指导。

  15. Nanoparticle optical notch filters

    Science.gov (United States)

    Kasinadhuni, Pradeep Kumar

    Developing novel light blocking products involves the design of a nanoparticle optical notch filter, working on the principle of localized surface plasmon resonance (LSPR). These light blocking products can be used in many applications. One such application is to naturally reduce migraine headaches and light sensitivity. Melanopsin ganglion cells present in the retina of the human eye, connect to the suprachiasmatic nucleus (SCN-the body's clock) in the brain, where they participate in the entrainment of the circadian rhythms. As the Melanopsin ganglion cells are involved in triggering the migraine headaches in photophobic patients, it is necessary to block the part of visible spectrum that activates these cells. It is observed from the action potential spectrum of the ganglion cells that they absorb light ranging from 450-500nm (blue-green part) of the visible spectrum with a λmax (peak sensitivity) of around 480nm (blue line). Currently prescribed for migraine patients is the FL-41 coating, which blocks a broad range of wavelengths, including wavelengths associated with melanopsin absorption. The nanoparticle optical notch filter is designed to block light only at 480nm, hence offering an effective prescription for the treatment of migraine headaches.

  16. Hydraulic Structures

    Data.gov (United States)

    Department of Homeland Security — This table is required whenever hydraulic structures are shown in the flood profile. It is also required if levees are shown on the FIRM, channels containing the...

  17. Notch sensitivity of aliphatic polyketone terpolymers

    NARCIS (Netherlands)

    Zuiderduin, W.C.J.; Huetink, J.; Gaymans, R.J.

    2004-01-01

    The notch sensitivity of aliphatic polyketone (PK) terpolymers was investigated in this article. The notch-tip radius was varied between the size of an actual propagating crack tip of 1-2 m and the largest notch tip of 1000 m radius. The larger notch-tip radii (1000-15 m) were milled into the polyme

  18. Notch1 and notch2 have opposite effects on embryonal brain tumor growth.

    Science.gov (United States)

    Fan, Xing; Mikolaenko, Irina; Elhassan, Ihab; Ni, Xingzhi; Wang, Yunyue; Ball, Douglas; Brat, Daniel J; Perry, Arie; Eberhart, Charles G

    2004-11-01

    The role of Notch signaling in tumorigenesis can vary; Notch1 acts as an oncogene in some neoplasms, and a tumor suppressor in others. Here, we show that different Notch receptors can have opposite effects in a single tumor type. Expression of truncated, constitutively active Notch1 or Notch2 in embryonal brain tumor cell lines caused antagonistic effects on tumor growth. Cell proliferation, soft agar colony formation, and xenograft growth were all promoted by Notch2 and inhibited by Notch1. We also found that Notch2 receptor transcripts are highly expressed in progenitor cell-derived brain tumors such as medulloblastomas, whereas Notch1 is scarce or undetectable. This parallels normal cerebellar development, during which Notch2 is predominantly expressed in proliferating progenitors and Notch1 in postmitotic differentiating cells. Given the oncogenic effects of Notch2, we analyzed its gene dosage in 40 embryonal brain tumors, detecting an increased copy number in 15% of cases. Notch2 gene amplification was confirmed by fluorescence in situ hybridization in one case with extremely high Notch2 mRNA levels. In addition, expression of the Notch pathway target gene Hes1 in medulloblastomas was associated with significantly shorter patient survival (P = 0.01). Finally, pharmacological inhibition of Notch signaling suppresses growth of medulloblastoma cells. Our data indicate that Notch1 and Notch2 can have opposite effects on the growth of a single tumor type, and show that Notch2 can be overexpressed after gene amplification in human tumors.

  19. PKCζ regulates Notch receptor routing and activity in a Notch signaling-dependent manner.

    Science.gov (United States)

    Sjöqvist, Marika; Antfolk, Daniel; Ferraris, Saima; Rraklli, Vilma; Haga, Cecilia; Antila, Christian; Mutvei, Anders; Imanishi, Susumu Y; Holmberg, Johan; Jin, Shaobo; Eriksson, John E; Lendahl, Urban; Sahlgren, Cecilia

    2014-04-01

    Activation of Notch signaling requires intracellular routing of the receptor, but the mechanisms controlling the distinct steps in the routing process is poorly understood. We identify PKCζ as a key regulator of Notch receptor intracellular routing. When PKCζ was inhibited in the developing chick central nervous system and in cultured myoblasts, Notch-stimulated cells were allowed to undergo differentiation. PKCζ phosphorylates membrane-tethered forms of Notch and regulates two distinct routing steps, depending on the Notch activation state. When Notch is activated, PKCζ promotes re-localization of Notch from late endosomes to the nucleus and enhances production of the Notch intracellular domain, which leads to increased Notch activity. In the non-activated state, PKCζ instead facilitates Notch receptor internalization, accompanied with increased ubiquitylation and interaction with the endosomal sorting protein Hrs. Collectively, these data identify PKCζ as a key regulator of Notch trafficking and demonstrate that distinct steps in intracellular routing are differentially modulated depending on Notch signaling status.

  20. Endosomal sorting of Notch receptors through COMMD9-dependent pathways modulates Notch signaling

    NARCIS (Netherlands)

    Li, H.; Koo, Y.; Mao, X.; Sifuentes-Dominguez, L.; Morris, L.L.; Jia, D.; Miyata, N; Faulkner, R.A.; Deursen, J.M.A. van; Vooijs, M.; Billadeau, D.D.; Sluis, B. van de; Cleaver, O.; Burstein, E.

    2015-01-01

    Notch family members are transmembrane receptors that mediate essential developmental programs. Upon ligand binding, a proteolytic event releases the intracellular domain of Notch, which translocates to the nucleus to regulate gene transcription. In addition, Notch trafficking across the endolysosom

  1. Notch2 and Notch3 Function Together to Regulate Vascular Smooth Muscle Development

    OpenAIRE

    Qingqing Wang; Ning Zhao; Simone Kennard; Brenda Lilly

    2012-01-01

    Notch signaling has been implicated in the regulation of smooth muscle differentiation, but the precise role of Notch receptors is ill defined. Although Notch3 receptor expression is high in smooth muscle, Notch3 mutant mice are viable and display only mild defects in vascular patterning and smooth muscle differentiation. Notch2 is also expressed in smooth muscle and Notch2 mutant mice show cardiovascular abnormalities indicative of smooth muscle defects. Together, these findings infer that N...

  2. FOUR NOTCH ROADLESS AREA, TEXAS.

    Science.gov (United States)

    Houser, B.B.; Ryan, George S.

    1984-01-01

    A geologic and geochemical investigation of the Four Notch Roadless Area, Texas, was conducted. The area has a probable resource potential for oil and gas. There is, however, little promise for the occurrence of metallic mineral resources or other energy resources. Acquisition of seismic data and detailed comparisons with logs from wells from the vicinity of the Four Notch Roadless Area is necessary to better determine if the subsurface stratigraphy and structures are favorable for the accumulation of oil or gas.

  3. Notch, lipids, and endothelial cells

    Science.gov (United States)

    Briot, Anaïs; Bouloumié, Anne; Iruela-Arispe, M. Luisa

    2017-01-01

    Purpose of review Notch signaling is an evolutionary conserved pathway critical for cardiovascular development and angiogenesis. More recently, the contribution of Notch signaling to the homeostasis of the adult vasculature has emerged as an important novel paradigm, but much remains to be understood. Recent findings Recent findings shed light on the impact of Notch in vascular and immune responses to microenvironmental signals as well as on the onset of atherosclerosis. In the past year, studies in human and mice explored the role of Notch in the maintenance of a nonactivated endothelium. Novel pieces of evidence suggest that this pathway is sensitive to environmental factors, including inflammatory mediators and diet-derived by-products. Summary An emerging theme is the ability of Notch to respond to changes in the microenvironment, including glucose and lipid metabolites. In turn, alterations in Notch enable an important link between metabolism and transcriptional changes, thus this receptor appears to function as a metabolic sensor with direct implications to gene expression. PMID:27454451

  4. Notch1 and Notch2 receptors regulate mouse and human gastric antral epithelial cell homoeostasis.

    Science.gov (United States)

    Gifford, Gail B; Demitrack, Elise S; Keeley, Theresa M; Tam, Andrew; La Cunza, Nilsa; Dedhia, Priya H; Spence, Jason R; Simeone, Diane M; Saotome, Ichiko; Louvi, Angeliki; Siebel, Christian W; Samuelson, Linda C

    2017-06-01

    We tested the ability of Notch pathway receptors Notch1 and Notch2 to regulate stem and epithelial cell homoeostasis in mouse and human gastric antral tissue. Mice were treated with the pan-Notch inhibitor dibenzazepine (DBZ) or inhibitory antibodies targeting Notch1 and/or Notch2. Epithelial proliferation, apoptosis and cellular differentiation were measured by histological and molecular approaches. Organoids were established from mouse and human antral glands; growth and differentiation were measured after treatment with Notch inhibitors. Notch1 and Notch2 are the predominant Notch receptors expressed in mouse and human antral tissue and organoid cultures. Combined inhibition of Notch1 and Notch2 in adult mice led to decreased epithelial cell proliferation, including reduced proliferation of LGR5 stem cells, and increased apoptosis, similar to the response to global Notch inhibition with DBZ. Less pronounced effects were observed after inhibition of individual receptors. Notch pathway inhibition with DBZ or combined inhibition of Notch1 and Notch2 led to increased differentiation of all gastric antral lineages, with remodelling of cells to express secretory products normally associated with other regions of the GI tract, including intestine. Analysis of mouse and human organoids showed that Notch signalling through Notch1 and Notch2 is intrinsic to the epithelium and required for organoid growth. Notch signalling is required to maintain gastric antral stem cells. Notch1 and Notch2 are the primary Notch receptors regulating epithelial cell homoeostasis in mouse and human stomach. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  5. Twin Jet

    Science.gov (United States)

    Henderson, Brenda; Bozak, Rick

    2010-01-01

    Many subsonic and supersonic vehicles in the current fleet have multiple engines mounted near one another. Some future vehicle concepts may use innovative propulsion systems such as distributed propulsion which will result in multiple jets mounted in close proximity. Engine configurations with multiple jets have the ability to exploit jet-by-jet shielding which may significantly reduce noise. Jet-by-jet shielding is the ability of one jet to shield noise that is emitted by another jet. The sensitivity of jet-by-jet shielding to jet spacing and simulated flight stream Mach number are not well understood. The current experiment investigates the impact of jet spacing, jet operating condition, and flight stream Mach number on the noise radiated from subsonic and supersonic twin jets.

  6. NOTCH1 and NOTCH2 regulate epithelial cell proliferation in mouse and human gastric corpus.

    Science.gov (United States)

    Demitrack, Elise S; Gifford, Gail B; Keeley, Theresa M; Horita, Nobukatsu; Todisco, Andrea; Turgeon, D Kim; Siebel, Christian W; Samuelson, Linda C

    2017-02-01

    The Notch signaling pathway is known to regulate stem cells and epithelial cell homeostasis in gastrointestinal tissues; however, Notch function in the corpus region of the stomach is poorly understood. In this study we examined the consequences of Notch inhibition and activation on cellular proliferation and differentiation and defined the specific Notch receptors functioning in the mouse and human corpus. Notch pathway activity was observed in the mouse corpus epithelium, and gene expression analysis revealed NOTCH1 and NOTCH2 to be the predominant Notch receptors in both mouse and human. Global Notch inhibition for 5 days reduced progenitor cell proliferation in the mouse corpus, as well as in organoids derived from mouse and human corpus tissue. Proliferation effects were mediated through both NOTCH1 and NOTCH2 receptors, as demonstrated by targeting each receptor alone or in combination with Notch receptor inhibitory antibodies. Analysis of differentiation by marker expression showed no change to the major cell lineages; however, there was a modest increase in the number of transitional cells coexpressing markers of mucous neck and chief cells. In contrast to reduced proliferation after pathway inhibition, Notch activation in the adult stomach resulted in increased proliferation coupled with reduced differentiation. These findings suggest that NOTCH1 and NOTCH2 signaling promotes progenitor cell proliferation in the mouse and human gastric corpus, which is consistent with previously defined roles for Notch in promoting stem and progenitor cell proliferation in the intestine and antral stomach. Here we demonstrate that the Notch signaling pathway is essential for proliferation of stem cells in the mouse and human gastric corpus. We identify NOTCH1 and NOTCH2 as the predominant Notch receptors expressed in both mouse and human corpus and show that both receptors are required for corpus stem cell proliferation. We show that chronic Notch activation in corpus stem

  7. The Expression of Notch 1 and Notch 3 in Gallbladder Cancer and Their Clinicopathological Significance.

    Science.gov (United States)

    Liu, Luyao; Yang, Zhu-Lin; Wang, Chunwei; Miao, Xiongying; Liu, Zhiyu; Li, Daiqiang; Zou, Qiong; Li, Jinghe; Liang, Lufeng; Zeng, Guixiang; Chen, Senlin

    2016-07-01

    Gallbladder cancers (GBCs) are highly malignant gastrointestinal cancers. The biological makers for the prognosis and targeting therapy of GBCs have not been established. The protein expression of Notch 1 and Notch 3 in 46 squamous cell/adenosquamous carcinomas (SC/ASCs) and 80 adenocarcinomas (AC) was measured using immunohistochemistry. Positive Notch 1 and Notch 3 expression in both SC/ASC and AC was significantly associated with large tumor size, invasion, metastasis, and low surgical curability (P Notch 1 and Notch 3 expression was significantly associated with mean survival of SC/ASC and AC patients (P Notch 1 and Notch 3 expression, as well as low differentiation, large tumor size, high TNM stage, invasion, lymph node metastasis, and surgical curability are independent poor-prognostic factors in both SC/ASC and AC patients. Positive Notch 1 and Notch 3 expression is closely correlated with severe clinicopathological characteristics and poor prognosis in both SC/ASC and AC patients.

  8. DOL behaviour of end-notched beams

    DEFF Research Database (Denmark)

    Gustafsson, P.J.; Hoffmeyer, Preben; Valentin, G.

    1998-01-01

    The long-term loading strength of end-notched beams made of glulam and LVL was tested. The beams were of various sizes, with and without a moisture sealing at the notch. Tests were conducted in open shelter climates, and at constant and cyclic relative humidity. The short-term strength was tested...... beams with a moisture sealing at the notch...

  9. Notch Signaling and Brain Tumors

    DEFF Research Database (Denmark)

    Stockhausen, Marie; Kristoffersen, Karina; Poulsen, Hans Skovgaard

    2011-01-01

    Human brain tumors are a heterogenous group of neoplasms occurring inside the cranium and the central spinal cord. In adults and children, astrocytic glioma and medulloblastoma are the most common subtypes of primary brain tumors. These tumor types are thought to arise from cells in which Notch...... signaling plays a fundamental role during development. Recent findings have shown that Notch signaling is dysregulated, and contributes to the malignant potential of these tumors. Growing evidence point towards an important role for cancer stem cells in the initiation and maintenance of glioma...

  10. Two-axis hydraulic joint for high speed, heavy lift robotic operations

    Energy Technology Data Exchange (ETDEWEB)

    Vaughn, M.R.; Robinett, R.D.; Phelan, J.R.; VanZuiden, D.M.

    1994-04-01

    A hydraulically driven universal joint was developed for a heavy lift, high speed nuclear waste remediation application. Each axis is driven by a simple hydraulic cylinder controlled by a jet pipe servovalve. Servovalve behavior is controlled by a force feedback control system, which damps the hydraulic resonance. A prototype single joint robot was built and tested. A two joint robot is under construction.

  11. Notch Signaling in Bone Regeneration

    Science.gov (United States)

    2011-10-01

    Notch delivery, a large animal model (e.g., sheep ) could be developed and tested in another 2 years. Within five years, we will have a product to...phenotype ( macrophage , endothelial cell, osteoblast, chondrocyte) using dual antibody labeling with antibodies for specific cell types. Additionally, we

  12. Notch Signaling and Brain Tumors

    DEFF Research Database (Denmark)

    Stockhausen, Marie; Kristoffersen, Karina; Poulsen, Hans Skovgaard

    2011-01-01

    Human brain tumors are a heterogenous group of neoplasms occurring inside the cranium and the central spinal cord. In adults and children, astrocytic glioma and medulloblastoma are the most common subtypes of primary brain tumors. These tumor types are thought to arise from cells in which Notch...

  13. Notch Signaling and Brain Tumors

    DEFF Research Database (Denmark)

    Stockhausen, Marie; Kristoffersen, Karina; Poulsen, Hans Skovgaard

    2011-01-01

    Human brain tumors are a heterogenous group of neoplasms occurring inside the cranium and the central spinal cord. In adults and children, astrocytic glioma and medulloblastoma are the most common subtypes of primary brain tumors. These tumor types are thought to arise from cells in which Notch...

  14. Jet observables without jet algorithms

    Energy Technology Data Exchange (ETDEWEB)

    Bertolini, Daniele; Chan, Tucker; Thaler, Jesse [Center for Theoretical Physics, Massachusetts Institute of Technology,Cambridge, MA 02139 (United States)

    2014-04-02

    We introduce a new class of event shapes to characterize the jet-like structure of an event. Like traditional event shapes, our observables are infrared/collinear safe and involve a sum over all hadrons in an event, but like a jet clustering algorithm, they incorporate a jet radius parameter and a transverse momentum cut. Three of the ubiquitous jet-based observables — jet multiplicity, summed scalar transverse momentum, and missing transverse momentum — have event shape counterparts that are closely correlated with their jet-based cousins. Due to their “local” computational structure, these jet-like event shapes could potentially be used for trigger-level event selection at the LHC. Intriguingly, the jet multiplicity event shape typically takes on non-integer values, highlighting the inherent ambiguity in defining jets. By inverting jet multiplicity, we show how to characterize the transverse momentum of the n-th hardest jet without actually finding the constituents of that jet. Since many physics applications do require knowledge about the jet constituents, we also build a hybrid event shape that incorporates (local) jet clustering information. As a straightforward application of our general technique, we derive an event-shape version of jet trimming, allowing event-wide jet grooming without explicit jet identification. Finally, we briefly mention possible applications of our method for jet substructure studies.

  15. Mechanical behaviors of notched composite laminates

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Presents the study on the mechanical behaviors of composite laminates with both static and fatigue tests per formed with different notched specimens and concludes with experimental results that ultimate strength and initial stiff ness of various notched composite laminates is almost as same as un-notched ones but the fatigue life of notched speci mens is much higher than un-notched ones. Compared with metals, composite materials are notch insensitive. The properties measured by using bar type specimens can not represent the real properties of composite laminates. Notches on the free edge may be helpful to the structure. The fatigue life can be predicted through theoretical models estab lished using the residual stiffness model.

  16. Anabolic actions of Notch on mature bone

    Science.gov (United States)

    Liu, Peng; Ping, Yilin; Ma, Meng; Zhang, Demao; Liu, Connie; Zaidi, Samir; Gao, Song; Ji, Yaoting; Lou, Feng; Yu, Fanyuan; Lu, Ping; Stachnik, Agnes; Bai, Mingru; Wei, Chengguo; Zhang, Liaoran; Wang, Ke; Chen, Rong; New, Maria I.; Rowe, David W.; Yuen, Tony; Sun, Li; Zaidi, Mone

    2016-01-01

    Notch controls skeletogenesis, but its role in the remodeling of adult bone remains conflicting. In mature mice, the skeleton can become osteopenic or osteosclerotic depending on the time point at which Notch is activated or inactivated. Using adult EGFP reporter mice, we find that Notch expression is localized to osteocytes embedded within bone matrix. Conditional activation of Notch signaling in osteocytes triggers profound bone formation, mainly due to increased mineralization, which rescues both age-associated and ovariectomy-induced bone loss and promotes bone healing following osteotomy. In parallel, mice rendered haploinsufficient in γ-secretase presenilin-1 (Psen1), which inhibits downstream Notch activation, display almost-absent terminal osteoblast differentiation. Consistent with this finding, pharmacologic or genetic disruption of Notch or its ligand Jagged1 inhibits mineralization. We suggest that stimulation of Notch signaling in osteocytes initiates a profound, therapeutically relevant, anabolic response. PMID:27036007

  17. NOTCH pathway inactivation promotes bladder cancer progression.

    Science.gov (United States)

    Maraver, Antonio; Fernandez-Marcos, Pablo J; Cash, Timothy P; Mendez-Pertuz, Marinela; Dueñas, Marta; Maietta, Paolo; Martinelli, Paola; Muñoz-Martin, Maribel; Martínez-Fernández, Mónica; Cañamero, Marta; Roncador, Giovanna; Martinez-Torrecuadrada, Jorge L; Grivas, Dimitrios; de la Pompa, Jose Luis; Valencia, Alfonso; Paramio, Jesús M; Real, Francisco X; Serrano, Manuel

    2015-02-01

    NOTCH signaling suppresses tumor growth and proliferation in several types of stratified epithelia. Here, we show that missense mutations in NOTCH1 and NOTCH2 found in human bladder cancers result in loss of function. In murine models, genetic ablation of the NOTCH pathway accelerated bladder tumorigenesis and promoted the formation of squamous cell carcinomas, with areas of mesenchymal features. Using bladder cancer cells, we determined that the NOTCH pathway stabilizes the epithelial phenotype through its effector HES1 and, consequently, loss of NOTCH activity favors the process of epithelial-mesenchymal transition. Evaluation of human bladder cancer samples revealed that tumors with low levels of HES1 present mesenchymal features and are more aggressive. Together, our results indicate that NOTCH serves as a tumor suppressor in the bladder and that loss of this pathway promotes mesenchymal and invasive features.

  18. Combined deficiency of Notch1 and Notch3 causes pericyte dysfunction, models CADASIL, and results in arteriovenous malformations

    OpenAIRE

    Kofler, Natalie M.; Henar Cuervo; Uh, Minji K.; Aino Murtomäki; Jan Kitajewski

    2015-01-01

    Pericytes regulate vessel stability and pericyte dysfunction contributes to retinopathies, stroke, and cancer. Here we define Notch as a key regulator of pericyte function during angiogenesis. In Notch1 +/−; Notch3 −/− mice, combined deficiency of Notch1 and Notch3 altered pericyte interaction with the endothelium and reduced pericyte coverage of the retinal vasculature. Notch1 and Notch3 were shown to cooperate to promote proper vascular basement membrane formation and contribute to endothel...

  19. Notching on Cancer’s Door: Notch Signaling in Brain Tumors

    OpenAIRE

    2015-01-01

    Notch receptors play an essential role in the regulation of central cellular processes during embryonic and postnatal development. The mammalian genome encodes for four Notch paralogs (Notch 1–4), which are activated by three Delta-like (Dll1/3/4) and two Serrate-like (Jagged1/2) ligands. Further, non-canonical Notch ligands such as epidermal growth factor like protein 7 (EGFL7) have been identified and serve mostly as antagonists of Notch signaling. The Notch pathway prevents neuronal differ...

  20. Notched strength of beryllium powder and ingot sheets.

    Science.gov (United States)

    Moss, R. G.

    1972-01-01

    The effects of notches in thin beryllium sheets were studied as functions of material variables and notch severity. Double edge notched samples having stress concentration factors of 1.0 to 15.4 were prepared by milling to size, etching, and electrical discharge machining the notches. Strength was not reduced greatly by sharp notches, and duller notches were more deleterious than sharp notches. The trend was for reduced strength for dull notches, increased strength for sharper notches, and reduced strength for very sharp notches. Differences in material purity or source of the sheet had little affect on notch sensitivity. The most important factors appear to be oxide content and directionality of the sheet microstructure; high oxide content and highly directional microstructure tend to give more notch sensitivity than low oxide content, and more bidirectional microstructure. Postulated causes of the change in notched/unnotched strength are given.

  1. Notch Signaling Inhibits Axon Regeneration

    OpenAIRE

    Bejjani, Rachid El; Hammarlund, Marc

    2012-01-01

    Many neurons have limited capacity to regenerate their axons after injury. Neurons in the mammalian CNS do not regenerate, and even neurons in the PNS often fail to regenerate to their former targets. This failure is likely due in part to pathways that actively restrict regeneration; however, only a few factors that limit regeneration are known. Here, using single-neuron analysis of regeneration in vivo, we show that Notch/lin-12 signaling inhibits the regeneration of mature C. elegans neuron...

  2. Steady-State Flow-Force Compensation in a Hydraulic Spool Valve

    CERN Document Server

    Lugowski, Jan

    2013-01-01

    A high-speed jet flowing inside of a partially-open hydraulic valve is accompanied by a reaction force, also referred to as flow force. The nature of this force has remained a mystery despite an extensive research effort spanning many decades. The momentum theory on the flow force by Lee and Blackburn (1952) explains the origin of the flow force and offers a design solution to shape the valve spool as a turbine bucket. It provides a model to calculate the compensated flow force as well. This paper shows that the model applies to a different flow case due to incorrect assumptions made. A corrected equation is presented based on a detailed analysis of the static-pressure distribution in the valve cavity as well as on a literature review of pressure loss in diffusers and nozzles. The new equation is based on the compensation taking place upstream of the valve orifice, not downstream as assumed by the momentum theory. The new model can be applied to chamfers or notches on the valve spool without the need to machi...

  3. The archetypal R90C CADASIL-NOTCH3 mutation retains NOTCH3 function in vivo.

    Science.gov (United States)

    Monet, Marie; Domenga, Valérie; Lemaire, Barbara; Souilhol, Céline; Langa, Francina; Babinet, Charles; Gridley, Thomas; Tournier-Lasserve, Elisabeth; Cohen-Tannoudji, Michel; Joutel, Anne

    2007-04-15

    Cerebral Autosomal Dominant Arteriopathy with Subcortical infarcts and Leukoencephalopathy (CADASIL) is the most prominent known cause of inherited stroke and vascular dementia in human adult. The disease gene, NOTCH3, encodes a transmembrane receptor primarily expressed in arterial smooth muscle cells (SMC). Pathogenic mutations lead to an odd number of cysteine residues within the NOTCH3 extracellular domain (NOTCH3(ECD)), and are associated with progressive accumulation of NOTCH3(ECD) at the SMC plasma membrane. The murine homolog, Notch3, is dispensable for viability but required post-natally for the elaboration and maintenance of arteries. How CADASIL-associated mutations impact NOTCH3 function remains a fundamental, yet unresolved issue. Particularly, whether NOTCH3(ECD) accumulation may titrate the ligand and inhibit the normal pathway is unknown. Herein, using genetic analyses in the mouse, we assessed the functional significance of an archetypal CADASIL-associated mutation (R90C), in vivo, in brain arteries. We show that transgenic mouse lines expressing either the wild-type human NOTCH3 or the mutant R90C human NOTCH3, at comparable and physiological levels, can rescue the arterial defects of Notch3-/- mice to similar degrees. In vivo assessment of NOTCH3/RBP-Jk activity provides evidence that the mutant NOTCH3 protein exhibits normal level of activity in brain arteries. Remarkably, the mutant NOTCH3 protein remains functional and does not exhibit dominant negative interfering activity, even when NOTCH3(ECD) accumulates. Collectively, these data suggest a model that invokes novel pathogenic roles for the mutant NOTCH3 protein rather than compromised NOTCH3 function as the primary determinant of the CADASIL arteriopathy.

  4. Assessment of correlation between knee notch width index and the three-dimensional notch volume

    NARCIS (Netherlands)

    van Eck, C.F.; Martins, C.A.Q.; Lorenz, S.G.F.; Fu, F.H.; Smolinski, P.

    2010-01-01

    This study was done to determine whether there is a correlation between the notch volume and the notch width index (NWI) as measured on the three most frequently used radiographic views: the Holmblad 45A degrees, Holmblad 70A degrees, and Rosenberg view. The notch volume of 20 cadaveric knees was me

  5. Involvement of notch signaling in wound healing.

    Directory of Open Access Journals (Sweden)

    Srinivasulu Chigurupati

    Full Text Available The Notch signaling pathway is critically involved in cell fate decisions during development of many tissues and organs. In the present study we employed in vivo and cell culture models to elucidate the role of Notch signaling in wound healing. The healing of full-thickness dermal wounds was significantly delayed in Notch antisense transgenic mice and in normal mice treated with gamma-secretase inhibitors that block proteolytic cleavage and activation of Notch. In contrast, mice treated with a Notch ligand Jagged peptide showed significantly enhanced wound healing compared to controls. Activation or inhibition of Notch signaling altered the behaviors of cultured vascular endothelial cells, keratinocytes and fibroblasts in a scratch wound healing model in ways consistent with roles for Notch signaling in wound healing functions all three cell types. These results suggest that Notch signaling plays important roles in wound healing and tissue repair, and that targeting the Notch pathway might provide a novel strategy for treatment of wounds and for modulation of angiogenesis in other pathological conditions.

  6. Notch Signaling Enhances Nestin Expression in Gliomas

    Directory of Open Access Journals (Sweden)

    Alan H. Shih

    2006-12-01

    Full Text Available Recent findings suggest that Notch signaling is active in brain tumors and stem cells, and that stem cells or cells with progenitor characteristics contribute to brain tumor formation. These stem cells are marked by expression of several markers, including nestin, an intermediate filament protein. We have studied how the Notch signaling pathway affects nestin expression in brain tumors. We find that Notch receptors and ligands are expressed in vitro and in human samples of glioblastomas, the highest grade of malignant gliomas. In culture, Notch activity activates the nestin promoter. Activation of the Notch pathway also occurs in a glioblastoma multiforme mouse model induced by Kras, with translational regulation playing a role in Notch expression. Combined activation of Notch and Kras in wild-type nestin-expressing cells leads to their expansion within the subventricular zone and retention of proliferation and nestin expression. However, activation of Notch alone is unable to induce this cellular expansion. These data suggest that Notch may have a contributing role in the stem-like character of glioma cells.

  7. Zebrafish phenotypic screen identifies novel Notch antagonists.

    Science.gov (United States)

    Velaithan, Vithya; Okuda, Kazuhide Shaun; Ng, Mei Fong; Samat, Norazwana; Leong, Sze Wei; Faudzi, Siti Munirah Mohd; Abas, Faridah; Shaari, Khozirah; Cheong, Sok Ching; Tan, Pei Jean; Patel, Vyomesh

    2017-04-01

    Zebrafish represents a powerful in vivo model for phenotype-based drug discovery to identify clinically relevant small molecules. By utilizing this model, we evaluated natural product derived compounds that could potentially modulate Notch signaling that is important in both zebrafish embryogenesis and pathogenic in human cancers. A total of 234 compounds were screened using zebrafish embryos and 3 were identified to be conferring phenotypic alterations similar to embryos treated with known Notch inhibitors. Subsequent secondary screens using HEK293T cells overexpressing truncated Notch1 (HEK293TΔE) identified 2 compounds, EDD3 and 3H4MB, to be potential Notch antagonists. Both compounds reduced protein expression of NOTCH1, Notch intracellular domain (NICD) and hairy and enhancer of split-1 (HES1) in HEK293TΔE and downregulated Notch target genes. Importantly, EDD3 treatment of human oral cancer cell lines demonstrated reduction of Notch target proteins and genes. EDD3 also inhibited proliferation and induced G0/G1 cell cycle arrest of ORL-150 cells through inducing p27(KIP1). Our data demonstrates the utility of the zebrafish phenotypic screen and identifying EDD3 as a promising Notch antagonist for further development as a novel therapeutic agent.

  8. Fuzzy jets

    Energy Technology Data Exchange (ETDEWEB)

    Mackey, Lester [Department of Statistics, Stanford University,Stanford, CA 94305 (United States); Nachman, Benjamin [Department of Physics, Stanford University,Stanford, CA 94305 (United States); SLAC National Accelerator Laboratory, Stanford University,2575 Sand Hill Rd, Menlo Park, CA 94025 (United States); Schwartzman, Ariel [SLAC National Accelerator Laboratory, Stanford University,2575 Sand Hill Rd, Menlo Park, CA 94025 (United States); Stansbury, Conrad [Department of Physics, Stanford University,Stanford, CA 94305 (United States)

    2016-06-01

    Collimated streams of particles produced in high energy physics experiments are organized using clustering algorithms to form jets. To construct jets, the experimental collaborations based at the Large Hadron Collider (LHC) primarily use agglomerative hierarchical clustering schemes known as sequential recombination. We propose a new class of algorithms for clustering jets that use infrared and collinear safe mixture models. These new algorithms, known as fuzzy jets, are clustered using maximum likelihood techniques and can dynamically determine various properties of jets like their size. We show that the fuzzy jet size adds additional information to conventional jet tagging variables in boosted topologies. Furthermore, we study the impact of pileup and show that with some slight modifications to the algorithm, fuzzy jets can be stable up to high pileup interaction multiplicities.

  9. Upregulation of Notch pathway molecules in oral squamous cell carcinoma

    OpenAIRE

    2010-01-01

    The constitutive activation of the Notch pathway has been demonstrated in various types of malignancies. However, it remains unclear how the Notch pathway is involved in the pathogenesis of oral squamous cell carcinoma (OSCC). We investigated the expression of Notch pathway molecules in OSCC cell lines and biopsy specimens and examined the effect of Notch pathway inhibition. Reverse transcription-polymerase chain reaction revealed upregulation of Notch1, Notch2, Jagged1, HES1 and HEY1 in both...

  10. High-cycle notch sensitivity of alloy steel ASTM A743 CA6NM used in hydrogenator turbine components

    Directory of Open Access Journals (Sweden)

    José Alexander Araújo

    2010-10-01

    Full Text Available The presence of notches and other stress concentrations in turbine blades and other notch hydraulic components is a current problem in engineering. It causes a reduction of endurance limit of material. In that sense, specimens of the ASTM A743 CA6NM alloy steel using in several hydrogenator turbine components was tested. The specimens were tested under uniaxial fatigue loading with a load ratio equal to -1, and the considered stress concentration factors, Kt, values, calculated with respect to net area, were 1.55, 2.04 and 2.42. In order to determine the fatigue limit for such notch type, a reduction data method by Dixon and Mood, Staircase method was used. This approach is based on the assumed target distribution of the fatigue limit. For such geometry at least 8 specimens were tested. In addition, the Peterson and Neuber’s notch fatigue factor were compared through fatigue notch reduction factor, Kf, obtained from experimental data. According to results obtained it was possible to conclude that the tested material is less sensitive to notches than the prediction of the Peterson and Neuber’s empirical models.

  11. Analytical Study on Impingement Heat Transfer with Single—Phase Free—Surface Circular Liquid Jets

    Institute of Scientific and Technical Information of China (English)

    C.F.Ma; T.Masuoka; 等

    1996-01-01

    An analytical research was conducted to study heat transfer from horizontal surfaces to normally impinging circular jets under arbitrary-heat-flux conditions.The laminar thermal and hydraulic bound ary layers were divided into five regions of flow.General expressions of heat transfer coefficients were obtained in all the four regions of stagnation and wall jet zones before the hydraulic jump.

  12. Notch receptors in human choroid plexus tumors.

    Science.gov (United States)

    Beschorner, R; Waidelich, J; Trautmann, K; Psaras, T; Schittenhelm, J

    2013-08-01

    Notch signaling plays a role in development and formation of the normal choroid plexus (nCP), and in formation of various tumors in humans. Activation of Notch3 has been reported to promote tumor growth in invasive gliomas and to initiate formation of choroid plexus tumors (CPT) in mice. We investigated the expression of all currently known Notch receptors (Notch 1-4) in 55 samples of nCP and 88 CPT, including 61 choroid plexus papillomas (CPP), 22 atypical CPP and 5 choroid plexus carcinomas by immunohistochemistry. Notch expression was semiquantitatively evaluated separately for membranous/cytoplasmic and for nuclear staining. In addition, we examined Her2 expression (EGFR2, Her2/neu, ErbB2, CD340) because of its functional link to Notch signaling. All samples were negative for Notch3. Membranous/cytoplasmic expression of Notch1 (pnCP compared to CPT. Nuclear expression of Notch1, -2 and -4 was significantly higher in CPT compared to nCP (pnCP to a predominant nuclear expression in CPT. Her2 was weakly expressed in 42/84 CPT but only in 2/53 nCP (p=0.0001) and positively correlated with nuclear expression of Notch1, -2 and 4 in CPT. In summary, a shift between membranous/cytoplasmic (non-canonical signaling pathway) and nuclear expression (canonical signaling pathway) of Notch1, -2 and -4 and upregulation of Her2 indicate neoplastic transformation in human CP and may reveal new therapeutic approaches.

  13. Notching on cancer’s door: Notch signaling in brain tumors

    Directory of Open Access Journals (Sweden)

    Marcin eTeodorczyk

    2015-01-01

    Full Text Available Notch receptors play an essential role in the regulation of central cellular processes during embryonic and postnatal development. The mammalian genome encodes for four Notch paralogs (Notch 1-4, which are activated by three Delta-like (Dll1/3/4 and two Serrate-like (Jagged1/2 ligands. Further, non-canonical Notch ligands such as EGFL7 have been identified and serve mostly as antagonists of Notch signaling. The Notch pathway prevents neuronal differentiation in the central nervous system by driving neural stem cell maintenance and commitment of neural progenitor cells into the glial lineage. Notch is therefore often implicated in the development of brain tumors, as tumor cells share various characteristics with neural stem and progenitor cells. Notch receptors are overexpressed in gliomas and their oncogenicity has been confirmed by gain- and loss-of-function studies in vitro and in vivo. To this end, special attention is paid to the impact of Notch signaling on stem-like brain tumor-propagating cells as these cells contribute to growth, survival, invasion and recurrence of brain tumors. Based on the outcome of ongoing studies in vivo, Notch-directed therapies such as γ secretase inhibitors and blocking antibodies have entered and completed various clinical trials. This review summarizes the current knowledge on Notch signaling in brain tumor formation and therapy.

  14. Active notch filter network with variable notch depth, width and frequency

    Science.gov (United States)

    Black, J. M. (Inventor)

    1980-01-01

    An active notch filter having independently adjustable notch frequency, width, and depth is provided by three equal capacitors connected in series with an operational amplifier (connected in a voltage follower configuration), a potentiometer across the series connected capacitors for notch depth adjustment, and a potentiometer (for notch frequency connected across the center capacitor); with its tap connected to receive a voltage feedback signal from a variable voltage divider comprised of another potentiometer for notch width. Adjusting the voltage dividing potentiometer will independently set the notch width, and adjusting the tap on the potentiometer across the center capacitor will independently adjust the notch frequency of the filter. A second operational amplifier connected in a voltage follower configuration may be used to connect the voltage divider output to the adjustable tap of the potentiometer across the center capacitor.

  15. Jet Observables Without Jet Algorithms

    CERN Document Server

    Bertolini, Daniele; Thaler, Jesse

    2013-01-01

    We introduce a new class of event shapes to characterize the jet-like structure of an event. Like traditional event shapes, our observables are infrared/collinear safe and involve a sum over all hadrons in an event, but like a jet clustering algorithm, they incorporate a jet radius parameter and a transverse momentum cut. Three of the ubiquitous jet-based observables---jet multiplicity, summed scalar transverse momentum, and missing transverse momentum---have event shape counterparts that are closely correlated with their jet-based cousins. Due to their "local" computational structure, these jet-like event shapes could potentially be used for trigger-level event selection at the LHC. Intriguingly, the jet multiplicity event shape typically takes on non-integer values, highlighting the inherent ambiguity in defining jets. By inverting jet multiplicity, we show how to characterize the transverse momentum of the n-th hardest jet without actually finding the constituents of that jet. Since many physics applicatio...

  16. Hydraulic conductivity and diffusion characterization of GCLs

    Energy Technology Data Exchange (ETDEWEB)

    Mukunoki, T.; Rowe, R.K.; Li, H.M.; Sangam, H.P.; Hurst, P.; Bathurst, R.J. [Queen' s Univ., Kingston, ON (Canada)]|[Royal Military Coll. of Canada, Kingston, ON (Canada); Badv, K. [Urmia Univ. (Iran, Islamic Republic of)

    2003-07-01

    This paper reports on the characterization of the hydraulic conductivity and diffusion of a geosynthetic clay liner (GCL) installed at a site off the southeast coast of Baffin Island, in the Canadian Arctic, following different levels of freeze-thaw exposure and under low temperature conditions. The authors presented a summary of the results obtained for hydraulic conductivity tests on GCLs subjected to freeze-thaw cycles, and specimens permeated with jet fuel (Arctic diesel). They also reported on diffusion tests conducted at 22 Celsius and 5 Celsius, followed by a discussion of the effect of temperature. The results indicate that there is no significant impact on GCL performance due to freeze-thaw cycles, permeation by jet fuel or diffusion at the lower temperatures expected in the north for the short term (up to approximately four years). Additional studies are needed to confirm long term behaviour. 24 refs., 2 tabs., 4 figs.

  17. Evidence of non-canonical NOTCH signaling

    DEFF Research Database (Denmark)

    Traustadóttir, Gunnhildur Ásta; Jensen, Charlotte H; Thomassen, Mads

    2016-01-01

    Dlk1(+/+) and Dlk1(-/-) mouse tissues at E16.5, we demonstrated that several NOTCH signaling pathways indeed are affected by DLK1 during tissue development, and this was supported by a lower activation of NOTCH1 protein in Dlk1(+/+) embryos. Likewise, but using a distinct Dlk1-manipulated (si...

  18. Targeting Notch to overcome radiation resistance.

    Science.gov (United States)

    Yahyanejad, Sanaz; Theys, Jan; Vooijs, Marc

    2016-02-16

    Radiotherapy represents an important therapeutic strategy in the treatment of cancer cells. However, it often fails to eliminate all tumor cells because of the intrinsic or acquired treatment resistance, which is the most common cause of tumor recurrence. Emerging evidences suggest that the Notch signaling pathway is an important pathway mediating radiation resistance in tumor cells. Successful targeting of Notch signaling requires a thorough understanding of Notch regulation and the context-dependent interactions between Notch and other therapeutically relevant pathways. Understanding these interactions will increase our ability to design rational combination regimens that are more likely to be safe and effective. Here we summarize the role of Notch in mediating resistance to radiotherapy, the different strategies to block Notch in cancer cells and how treatment scheduling can improve tumor response. Finally, we discuss a need for reliable Notch related biomarkers in specific tumors to measure pathway activity and to allow identification of a subset of patients who are likely to benefit from Notch targeted therapies.

  19. Identification of Domains for Efficient Notch Signaling Activity in Immobilized Notch Ligand Proteins.

    Science.gov (United States)

    Liu, Ledi; Wada, Hiroe; Matsubara, Natsuki; Hozumi, Katsuto; Itoh, Motoyuki

    2017-04-01

    Notch is a critical signaling pathway that controls cell fate and tissue homeostasis, but the functional characterization of Notch ligand domains that activate Notch receptors remains incomplete. Here, we established a method for immobilizing Notch ligand proteins onto beads to measure time-dependent Notch activity after the addition of Notch ligand-coated beads. A comparison between activities by the Notch ligand found on the cell surface to that of the ligand immobilized on beads showed that immobilized Notch ligand protein produces comparable signal activity during the first 10 h. Follow-up truncation studies showed that the N-terminal epidermal growth factor (EGF) repeat three region of delta like canonical Notch ligand 4 (DLL4) or jagged 1 (JAG1) is the minimum region for activating Notch signaling, and the DLL4 EGF repeat three domain may have a role in activation through a mechanism other than by increasing binding affinity. In addition, we found that reconstruction of the DLL4 delta and OSM-11 (DOS) motif (N257P) resulted in an increase in both binding affinity and signaling activity, which suggests that the role of the DOS motif is conserved among Notch ligands. Furthermore, active DLL4 protein on beads promoted T cell differentiation or inhibited B cell differentiation in vitro, whereas JAG1 proteins on beads did not have any effect. Taken together, our findings provide unambiguous evidence for the role of different Notch ligands and their domains in Notch signal activation, and may be potential tools for controlling Notch signaling activation. J. Cell. Biochem. 118: 785-796, 2017. © 2016 Wiley Periodicals, Inc.

  20. [Abnormal Notch-Hes Signaling Pathways and Acute Leukemia -Review].

    Science.gov (United States)

    Gu, Zhen-Yang; Wang, Li; Gao, Chun-Ji

    2017-02-01

    The abnormal activation of Notch signaling is closely related to the development of acute leukemia (AL). The core elements of the Notch signaling system include Notch receptors, Notch ligands, CSL DNA-binding proteins, and effectors like target genes. Any factors, which affect ligands, receptors, signal transducers and effectors, can influence the signal transduction of Notch signaling greatly. Based on the role of Notch signaling in AL, several targeted drugs against Notch upstream signaling have been developed. However, due to the complexity and pleiotropic effects of Notch upstream signaling, these targeted drugs display strong side effects. Thus, Hes (Hairy Enhancer of Split) factors as a primary Notch effector, also play an important role in the pathogenesis of AL. This review summarizes recent progresses on Notch-Hes signaling in AL, hopping to provide references for further excavation of the Notch-Hes signaling, and lay foundations for developing the next generation of targeted drugs.

  1. The Notch pathway in colorectal cancer.

    Science.gov (United States)

    Vinson, Kaitlyn E; George, Dennis C; Fender, Alexander W; Bertrand, Fred E; Sigounas, George

    2016-04-15

    Colorectal cancer (CRC) is the third leading cause of cancer death worldwide. It is also the third most common cancer diagnosis among men, and the second most common cancer diagnosis among women. Globally, CRC can account for nearly 694,000 annual deaths. It is widely appreciated that CRC is the result of dysregulated cellular pathways that promote an inappropriate stem-cell-like phenotype, apoptotic resistance, unchecked proliferation and metastatic spread. While no single pathway is responsible for all of these attributes, an array of recent studies suggests a pivotal role for abnormal Notch-1 signaling in CRC, in part due to interconnectivity of Notch with other pathways. This review will summarize recent evidence for a role of Notch signaling in CRC, will consider interconnectivity between Notch and other pathways involved in CRC and will discuss the possible utility of targeting Notch as a CRC therapeutic.

  2. Characterization of Notch1 antibodies that inhibit signaling of both normal and mutated Notch1 receptors.

    Directory of Open Access Journals (Sweden)

    Miguel Aste-Amézaga

    Full Text Available Notch receptors normally play a key role in guiding a variety of cell fate decisions during development and differentiation of metazoan organisms. On the other hand, dysregulation of Notch1 signaling is associated with many different types of cancer as well as tumor angiogenesis, making Notch1 a potential therapeutic target.Here we report the in vitro activities of inhibitory Notch1 monoclonal antibodies derived from cell-based and solid-phase screening of a phage display library. Two classes of antibodies were found, one directed against the EGF-repeat region that encompasses the ligand-binding domain (LBD, and the second directed against the activation switch of the receptor, the Notch negative regulatory region (NRR. The antibodies are selective for Notch1, inhibiting Jag2-dependent signaling by Notch1 but not by Notch 2 and 3 in reporter gene assays, with EC(50 values as low as 5+/-3 nM and 0.13+/-0.09 nM for the LBD and NRR antibodies, respectively, and fail to recognize Notch4. While more potent, NRR antibodies are incomplete antagonists of Notch1 signaling. The antagonistic activity of LBD, but not NRR, antibodies is strongly dependent on the activating ligand. Both LBD and NRR antibodies bind to Notch1 on human tumor cell lines and inhibit the expression of sentinel Notch target genes, including HES1, HES5, and DTX1. NRR antibodies also strongly inhibit ligand-independent signaling in heterologous cells transiently expressing Notch1 receptors with diverse NRR "class I" point mutations, the most common type of mutation found in human T-cell acute lymphoblastic leukemia (T-ALL. In contrast, NRR antibodies failed to antagonize Notch1 receptors bearing rare "class II" or "class III" mutations, in which amino acid insertions generate a duplicated or constitutively sensitive metalloprotease cleavage site. Signaling in T-ALL cell lines bearing class I mutations is partially refractory to inhibitory antibodies as compared to cell

  3. Notch3/Jagged1 Circuitry Reinforces Notch Signaling and Sustains T-ALL

    Directory of Open Access Journals (Sweden)

    Maria Pelullo

    2014-12-01

    Full Text Available Deregulated Notch signaling has been extensively linked to T-cell acute lymphoblastic leukemia (T-ALL. Here, we show a direct relationship between Notch3 receptor and Jagged1 ligand in human cell lines and in a mouse model of T-ALL. We provide evidence that Notch-specific ligand Jagged1 is a new Notch3 signaling target gene. This essential event justifies an aberrant Notch3/Jagged1 cis-expression inside the same cell. Moreover, we demonstrate in Notch3-IC–overexpressing T lymphoma cells that Jagged1 undergoes a raft-associated constitutive processing. The proteolytic cleavage allows the Jagged1 intracellular domain to empower Notch signaling activity and to increase the transcriptional activation of Jagged1 itself (autocrine effect. On the other hand, the release of the soluble Jagged1 extracellular domain has a positive impact on activating Notch signaling in adjacent cells (paracrine effect, finally giving rise to a Notch3/Jagged1 auto-sustaining loop that supports the survival, proliferation, and invasion of lymphoma cells and contributes to the development and progression of Notch-dependent T-ALL. These observations are also supported by a study conducted on a cohort of patients in which Jagged1 expression is associated to adverse prognosis.

  4. HYDRAULICS, LOUISA COUNTY, USA

    Data.gov (United States)

    Federal Emergency Management Agency, Department of Homeland Security — Hydraulic data include spatial datasets and data tables necessary for documenting the hydraulic analysis for estimating flood stages for a flood insurance study. It...

  5. Hydraulic Hybrid Vehicles

    Science.gov (United States)

    EPA and the United Parcel Service (UPS) have developed a hydraulic hybrid delivery vehicle to explore and demonstrate the environmental benefits of the hydraulic hybrid for urban pick-up and delivery fleets.

  6. Notch signaling in acute promyelocytic leukemia.

    Science.gov (United States)

    Grieselhuber, N R; Klco, J M; Verdoni, A M; Lamprecht, T; Sarkaria, S M; Wartman, L D; Ley, T J

    2013-07-01

    Acute promyelocytic leukemia (APL) is initiated by the PML-RARA (PR) fusion oncogene and has a characteristic expression profile that includes high levels of the Notch ligand Jagged-1 (JAG1). In this study, we used a series of bioinformatic, in vitro, and in vivo assays to assess the role of Notch signaling in human APL samples, and in a PML-RARA knock-in mouse model of APL (Ctsg-PML-RARA). We identified a Notch expression signature in both human primary APL cells and in Kit+Lin-Sca1+ cells from pre-leukemic Ctsg-PML-RARA mice. Both genetic and pharmacologic inhibition of Notch signaling abrogated the enhanced self-renewal seen in hematopoietic stem/progenitor cells from pre-leukemic Ctsg-PML-RARA mice, but had no influence on cells from age-matched wild-type mice. In addition, six of nine murine APL tumors tested displayed diminished growth in vitro when Notch signaling was inhibited pharmacologically. Finally, we found that genetic inhibition of Notch signaling with a dominant-negative Mastermind-like protein reduced APL growth in vivo in a subset of tumors. These findings expand the role of Notch signaling in hematopoietic diseases, and further define the mechanistic events important for PML-RARA-mediated leukemogenesis.

  7. The role of Notch signaling in kidney podocytes.

    Science.gov (United States)

    Asanuma, Katsuhiko; Oliva Trejo, Juan Alejandro; Tanaka, Eriko

    2017-02-01

    The Notch signaling pathway is a basic cell-to-cell communication mechanism. This pathway is activated by the interaction between Notch receptors and the ligands of adjacent cells. Once activated, Notch receptors are cleaved and the intracellular domains translocate into the nucleus, where the transcription of target genes starts. In the mammalian kidney, Notch receptors are activated during nephrogenesis. Afterwards, in the mature glomeruli, the Notch pathway becomes silent. However, many researchers have reported the activation of Notch receptors in mature podocytes under pathological conditions. In this review, we discuss the role of Notch signaling in podocytes.

  8. Comparative analysis of Notch1 and Notch2 binding sites in the genome of BxPC3 pancreatic cancer cells

    OpenAIRE

    Liu, Hao; Zhou, Ping; Lan, Hong; Chen, Jia; Yu-xiang ZHANG

    2017-01-01

    Notch signaling plays a key role in the development of pancreatic cancer. Among the four identified Notch receptors, Notch1 and Notch2 share the highest homology. Notch1 has been reported to be an oncogene but some reports indicate that Notch2, not Notch1, plays a key role in pancreatic carcinogenesis. As both are transcription factors, examination of their genomic binding sites might reveal interesting functional differences between them. Notch proteins do not have DNA-binding domain. In the...

  9. 76 FR 22745 - Three Notch Railway, LLC-Acquisition and Operation Exemption-Three Notch Railroad Co., Inc.

    Science.gov (United States)

    2011-04-22

    ... Surface Transportation Board Three Notch Railway, LLC--Acquisition and Operation Exemption-- Three Notch Railroad Co., Inc. Three Notch Railway, LLC (TNRW), a noncarrier, has filed a verified notice of exemption under 49 CFR 1150.31 to acquire from Three Notch Railroad Co., Inc. (TNHR) and to operate approximately...

  10. Study and application of a high-pressure water jet multi-functional flow test system

    Science.gov (United States)

    Shi, Huaizhong; Li, Gensheng; Huang, Zhongwei; Li, Jingbin; Zhang, Yi

    2015-12-01

    As the exploration and development of oil and gas focus more and more on deeper formation, hydraulic issues such as high-pressure water jet rock breaking, wellbore multiphase flow law, cuttings carrying efficiency, and hydraulic fracturing technique during the drilling and completion process have become the key points. To accomplish related researches, a high-pressure water jet multi-functional flow test system was designed. The following novel researches are carried out: study of high-pressure water jet characteristics under confining pressure, wellbore multiphase flow regime, hydraulic pressure properties of down hole tools during jet fracturing and pulsed cavitation jet drilling, and deflector's friction in radial jet drilling. The validity and feasibility of the experimental results provided by the system with various test modules have proved its importance in the research of the high-pressure water jet and well completion technology.

  11. NUMERICAL SIMULATION OF 3-D AERATED JET BEHIND FLIP BUCKET OF OVERFLOW DAM

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Aerated jet,such as the jet flow behind the flip bucket of an overflow dam, widely exists in hydraulic engineering. Up to now the model test and prototype observation have been two main methods of studying the aerated jet for a special hydraulic project. In this paper, a three-dimensional mathematical model for the aerated jet was established. It seems that the suggested model has high predictive power by comparison with the results of model tests and prototype observations, which is very useful in the study of energy dissipation and jet flow atomization.

  12. Notch and the awesome power of genetics.

    Science.gov (United States)

    Greenwald, Iva

    2012-07-01

    Notch is a receptor that mediates cell-cell interactions in animal development, and aberrations in Notch signal transduction can cause cancer and other human diseases. Here, I describe the major advances in the Notch field from the identification of the first mutant in Drosophila almost a century ago through the elucidation of the unusual mechanism of signal transduction a little over a decade ago. As an essay for the GENETICS Perspectives series, it is my personal and critical commentary as well as an historical account of discovery.

  13. Notch sensitivity of space shuttle tile materials

    Science.gov (United States)

    Newman, J. C., Jr.

    1980-01-01

    Tests were conducted at room temperature to determine the notch sensitivity of the thermal protection tile for the space shuttle. Two types of RSI tile were studied: LI-900 and LI-2200. Three point bend specimens were cut from discarded tiles in the in-plane (ip) and through-the-thickness (ttt) directions. They were tested with or without a sharp notch. The LI-900 (ip and ttt) specimens were not very notch sensitive, but the LI-2200 (ip and ttt) specimens were. The LI-2200 material showed about a 35 percent reduction in strength due to the presence of the notch. This reduction in strength should be considered in the design of mechanically fastened tile concepts.

  14. Notch Promotes Radioresistance of Glioma Stem Cells

    OpenAIRE

    Wang, Jialiang; Wakeman, Timothy P.; Latha, Justin D.; Hjelmeland, Anita B.; Wang, Xiao-Fan; White, Rebekah R.; Rich, Jeremy N.; Sullenger, Bruce A.

    2010-01-01

    Radiotherapy represents the most effective nonsurgical treatments for gliomas. Yet, gliomas are highly radioresistant and recurrence is nearly universal. Results from our laboratory and other groups suggest that cancer stem cells contribute to radioresistance in gliomas and breast cancers. The Notch pathway is critically implicated in stem cell fate determination and cancer. In this study, we showed that inhibition of Notch pathway with gamma-secretase inhibitors (GSIs) rendered the glioma st...

  15. Notch Signaling in Vascular Smooth Muscle Cells.

    Science.gov (United States)

    Baeten, J T; Lilly, B

    2017-01-01

    The Notch signaling pathway is a highly conserved pathway involved in cell fate determination in embryonic development and also functions in the regulation of physiological processes in several systems. It plays an especially important role in vascular development and physiology by influencing angiogenesis, vessel patterning, arterial/venous specification, and vascular smooth muscle biology. Aberrant or dysregulated Notch signaling is the cause of or a contributing factor to many vascular disorders, including inherited vascular diseases, such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, associated with degeneration of the smooth muscle layer in cerebral arteries. Like most signaling pathways, the Notch signaling axis is influenced by complex interactions with mediators of other signaling pathways. This complexity is also compounded by different members of the Notch family having both overlapping and unique functions. Thus, it is vital to fully understand the roles and interactions of each Notch family member in order to effectively and specifically target their exact contributions to vascular disease. In this chapter, we will review the Notch signaling pathway in vascular smooth muscle cells as it relates to vascular development and human disease.

  16. 径向射流水力压裂技术在高瓦斯矿井立井揭煤中的应用%Application of Radial Jet Hydraulic Pressurized Fracturing Technology to Seam Opening of High Gassy Mine Shaft

    Institute of Scientific and Technical Information of China (English)

    李翔; 刘林松

    2016-01-01

    Nansu Mine Income Ventilation Shaft of Zhaozhuang Mine had a designed depth of 784.5 m. When the mine shaft construction was at a depth of 724.17 m ,the mine shaft sinking was stopped. The radial jet hydraulic pressurized fracturing technology was applied to the seam opening operation of an underneath No.3 seam (high gassy seam ). After the hydraulic pressurized fracturing ,the gas pre-drainage was only conducted with 35 days and the seam had the seam opening conditions. The practices showed that the fracturing technology could play a well role to the seam permeability improved ,stress released and seam pressure bump elimination. In comparison with the conventional seam opening meth‐od ,the fracturing technology could safely and rapidly make the seam with the seam opening condi‐tions.%赵庄矿南苏进风立井设计深度784.5 m。井筒施工至724.17 m深处时,停止掘进,应用径向射流水力压裂技术,对下部的3号煤层(高瓦斯煤层)进行揭煤作业。水力压裂后,仅预抽35 d ,便使煤层具备揭煤条件。实践表明,该项技术对煤层增透、应力释放、消突可起到很好的作用,与传统揭煤方法相比,能安全快速地使煤层具备揭煤条件。

  17. The role of Notch in the cardiovascular system: potential adverse effects of investigational Notch inhibitors

    Directory of Open Access Journals (Sweden)

    Paola eRizzo

    2015-01-01

    Full Text Available Targeting the Notch pathway is a new promising therapeutic approach for cancer patients. Inhibition of Notch is effective in the oncology setting because it causes a reduction of highly proliferative tumor cells and it inhibits survival of cancer stem cells which are considered responsible for tumor recurrence and metastasis. Additionally, since Delta- like ligand 4 (Dll4- activated Notch signalling is a major modulator of angiogenesis, anti-Dll4 agents are being investigated to reduce vascularization of the tumor. Notch plays a major role in the heart during the development and, after birth, in response to cardiac damage. Therefore, agents used to inhibit Notch in the tumors (gamma secretase inhibitors and anti-Dll4 agents could potentially affect myocardial repair. The past experience with trastuzumab and other tyrosine kinase inhibitors used for cancer therapy demonstrates that the possible cardiotoxicity of agents targeting shared pathways between cancer and heart and the vasculature should be considered. To date, Notch inhibition in cancer patients has resulted only in mild gastrointestinal toxicity. Little is known about the potential long term cardiotoxicity associated to Notch inhibition in cancer patients. In this review we will focus on mechanisms through which inhibition of Notch signalling could lead to cardiomyocytes and endothelial dysfunctions. These adverse effects could contrast with the benefits of therapeutic responses in cancer cells during times of increased cardiac stress and/or in the presence of cardiovascular risk factor

  18. MAGP2 controls Notch via interactions with RGD binding integrins: Identification of a novel ECM-integrin-Notch signaling axis.

    Science.gov (United States)

    Deford, Peter; Brown, Kasey; Richards, Rae Lee; King, Aric; Newburn, Kristin; Westover, Katherine; Albig, Allan R

    2016-02-01

    Canonical Notch signaling involves Notch receptor activation via interaction with cell surface bound Notch ligand. Recent findings also indicate that Notch signaling may be modulated by cross-talk with other signaling mechanisms. The ECM protein MAGP2 was previously shown to regulate Notch in a cell type dependent manner, although the molecular details of this interaction have not been dissected. Here, we report that MAGP2 cell type specific control of Notch is independent of individual Notch receptor-ligand combinations but dependent on interaction with RGD binding integrins. Overexpressed MAGP2 was found to suppress transcriptional activity from the Notch responsive Hes1 promoter activity in endothelial cells, while overexpression of a RGD→RGE MAGP2 mutant increased Notch signaling in the same cell type. This effect was not unique to MAGP2 since the RGD domain of the ECM protein EGFL7 was also found to be an important modulator of Hes1 promoter activity. Independently of MAGP2 or EGFL7, inhibition of RGD-binding integrins with soluble RGD peptides also increased accumulation of active N1ICD fragments and Notch responsive promoter activity independently of changes in Notch1, Jag1, or Dll4 expression. Finally, β1 or β3 integrin blocking antibodies also enhanced Notch signaling. Collectively, these results answer the question of how MAGP2 controls cell type dependent Notch signaling, but more importantly uncover a new mechanism to understand how extracellular matrices and cellular environments impact Notch signaling.

  19. Targeting Notch to target cancer stem cells.

    Science.gov (United States)

    Pannuti, Antonio; Foreman, Kimberly; Rizzo, Paola; Osipo, Clodia; Golde, Todd; Osborne, Barbara; Miele, Lucio

    2010-06-15

    The cellular heterogeneity of neoplasms has been at the center of considerable interest since the "cancer stem cell hypothesis", originally formulated for hematologic malignancies, was extended to solid tumors. The origins of cancer "stem" cells (CSC) or tumor-initiating cells (TIC; henceforth referred to as CSCs) and the methods to identify them are hotly debated topics. Nevertheless, the existence of subpopulations of tumor cells with stem-like characteristics has significant therapeutic implications. The stem-like phenotype includes indefinite self-replication, pluripotency, and, importantly, resistance to chemotherapeutics. Thus, it is plausible that CSCs, regardless of their origin, may escape standard therapies and cause disease recurrences and/or metastasis after apparently complete remissions. Consequently, the idea of selectively targeting CSCs with novel therapeutics is gaining considerable interest. The Notch pathway is one of the most intensively studied putative therapeutic targets in CSC, and several investigational Notch inhibitors are being developed. However, successful targeting of Notch signaling in CSC will require a thorough understanding of Notch regulation and the context-dependent interactions between Notch and other therapeutically relevant pathways. Understanding these interactions will increase our ability to design rational combination regimens that are more likely to prove safe and effective. Additionally, to determine which patients are most likely to benefit from treatment with Notch-targeting therapeutics, reliable biomarkers to measure pathway activity in CSC from specific tumors will have to be identified and validated. This article summarizes the most recent developments in the field of Notch-targeted cancer therapeutics, with emphasis on CSC.

  20. Jet quenching via jet collimation

    CERN Document Server

    Casalderrey-Solana, J; Wiedemann, U

    2011-01-01

    The strong modifications of dijet properties in heavy ion collisions measured by ATLAS and CMS provide important constraints on the dynamical mechanisms underlying jet quenching. In this work, we show that the transport of soft gluons away from the jet cone - jet collimation - can account for the observed dijet asymmetry with values of $\\hat{q}\\, L$ that lie in the expected order of magnitude. Further, we show that the energy loss attained through this mechanism results in a very mild distortion of the azimuthal angle dijet distribution.

  1. Emerging jets

    Energy Technology Data Exchange (ETDEWEB)

    Schwaller, Pedro; Stolarski, Daniel [European Organization for Nuclear Research (CERN), Geneva (Switzerland). TH-PH Div.; Weiler, Andreas [European Organization for Nuclear Research (CERN), Geneva (Switzerland). TH-PH Div.; Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2015-02-15

    In this work, we propose a novel search strategy for new physics at the LHC that utilizes calorimeter jets that (i) are composed dominantly of displaced tracks and (ii) have many different vertices within the jet cone. Such emerging jet signatures are smoking guns for models with a composite dark sector where a parton shower in the dark sector is followed by displaced decays of dark pions back to SM jets. No current LHC searches are sensitive to this type of phenomenology. We perform a detailed simulation for a benchmark signal with two regular and two emerging jets, and present and implement strategies to suppress QCD backgrounds by up to six orders of magnitude. At the 14 TeV LHC, this signature can be probed with mediator masses as large as 1.5 TeV for a range of dark pion lifetimes, and the reach is increased further at the high-luminosity LHC. The emerging jet search is also sensitive to a broad class of long-lived phenomena, and we show this for a supersymmetric model with R-parity violation. Possibilities for discovery at LHCb are also discussed.

  2. Emerging Jets

    CERN Document Server

    Schwaller, Pedro; Weiler, Andreas

    2015-01-01

    In this work, we propose a novel search strategy for new physics at the LHC that utilizes calorimeter jets that (i) are composed dominantly of displaced tracks and (ii) have many different vertices within the jet cone. Such emerging jet signatures are smoking guns for models with a composite dark sector where a parton shower in the dark sector is followed by displaced decays of dark pions back to SM jets. No current LHC searches are sensitive to this type of phenomenology. We perform a detailed simulation for a benchmark signal with two regular and two emerging jets, and present and implement strategies to suppress QCD backgrounds by up to six orders of magnitude. At the 14 TeV LHC, this signature can be probed with mediator masses as large as 1.5 TeV for a range of dark pion lifetimes, and the reach is increased further at the high-luminosity LHC. The emerging jet search is also sensitive to a broad class of long-lived phenomena, and we show this for a supersymmetric model with R-parity violation. Possibilit...

  3. Prox1 regulates the notch1-mediated inhibition of neurogenesis.

    Directory of Open Access Journals (Sweden)

    Valeria Kaltezioti

    Full Text Available Activation of Notch1 signaling in neural progenitor cells (NPCs induces self-renewal and inhibits neurogenesis. Upon neuronal differentiation, NPCs overcome this inhibition, express proneural genes to induce Notch ligands, and activate Notch1 in neighboring NPCs. The molecular mechanism that coordinates Notch1 inactivation with initiation of neurogenesis remains elusive. Here, we provide evidence that Prox1, a transcription repressor and downstream target of proneural genes, counteracts Notch1 signaling via direct suppression of Notch1 gene expression. By expression studies in the developing spinal cord of chick and mouse embryo, we showed that Prox1 is limited to neuronal precursors residing between the Notch1+ NPCs and post-mitotic neurons. Physiological levels of Prox1 in this tissue are sufficient to allow binding at Notch1 promoter and they are critical for proper Notch1 transcriptional regulation in vivo. Gain-of-function studies in the chick neural tube and mouse NPCs suggest that Prox1-mediated suppression of Notch1 relieves its inhibition on neurogenesis and allows NPCs to exit the cell cycle and differentiate. Moreover, loss-of-function in the chick neural tube shows that Prox1 is necessary for suppression of Notch1 outside the ventricular zone, inhibition of active Notch signaling, down-regulation of NPC markers, and completion of neuronal differentiation program. Together these data suggest that Prox1 inhibits Notch1 gene expression to control the balance between NPC self-renewal and neuronal differentiation.

  4. Notch receptor expression in human brain arteriovenous malformations.

    Science.gov (United States)

    Hill-Felberg, Sandra; Wu, Hope Hueizhi; Toms, Steven A; Dehdashti, Amir R

    2015-08-01

    The roles of the Notch pathway proteins in normal adult vascular physiology and the pathogenesis of brain arteriovenous malformations are not well-understood. Notch 1 and 4 have been detected in human and mutant mice vascular malformations respectively. Although mutations in the human Notch 3 gene caused a genetic form of vascular stroke and dementia, its role in arteriovenous malformations development has been unknown. In this study, we performed immunohistochemistry screening on tissue microarrays containing eight surgically resected human brain arteriovenous malformations and 10 control surgical epilepsy samples. The tissue microarrays were evaluated for Notch 1-4 expression. We have found that compared to normal brain vascular tissue Notch-3 was dramatically increased in brain arteriovenous malformations. Similarly, Notch 4 labelling was also increased in vascular malformations and was confirmed by western blot analysis. Notch 2 was not detectable in any of the human vessels analysed. Using both immunohistochemistry on microarrays and western blot analysis, we have found that Notch-1 expression was detectable in control vessels, and discovered a significant decrease of Notch 1 expression in vascular malformations. We have demonstrated that Notch 3 and 4, and not Notch 1, were highly increased in human arteriovenous malformations. Our findings suggested that Notch 4, and more importantly, Notch 3, may play a role in the development and pathobiology of human arteriovenous malformations.

  5. Differential expression of Notch family members in astrocytomas and medulloblastomas.

    Science.gov (United States)

    Xu, Peng; Yu, Shizhu; Jiang, Rongcai; Kang, Chunsheng; Wang, Guangxiu; Jiang, Hao; Pu, Peiyu

    2009-12-01

    Notch signaling pathway plays an integral role in determining cell fates in development. Growing evidence demonstrates that Notch signaling pathway has versatile effects in tumorigenesis depending on the tumor type, grade and stage. Notch signaling pathway is deregulated in some brain tumors. To examine the differential expression of Notch family members (Notch1, 2, 3, 4) in human astrocytomas and medulloblastomas, and to evaluate their roles in the development of both tumor types. Immunohistochemical staining and Western blot analysis were used to detect Notch1, 2, 3, 4 expression in tissue microarray and freshly resected tissue samples of normal brain, astrocytomas and medulloblastomas. Notch family members were not expressed or barely detectable in normal brain tissues. Notch1, 3, 4 were highly expressed but Notch2 was not expressed in astrocytomas. The percentage of immunopositive tumor cells and level of Notch1 expression was increased with tumor grade. In addition, overexpression of Notch2 was detected in medulloblastomas in contrast to low or no expression of Notch1, 3, 4. Differential expression of Notch1, 2, 3, 4 is detected in astrocytomas and medulloblastomas, that may be related to their different roles playing in the development of brain tumors.

  6. Notch1 functions as a tumor suppressor in mouse skin.

    Science.gov (United States)

    Nicolas, Michael; Wolfer, Anita; Raj, Kenneth; Kummer, J Alain; Mill, Pleasantine; van Noort, Mascha; Hui, Chi-chung; Clevers, Hans; Dotto, G Paolo; Radtke, Freddy

    2003-03-01

    Notch proteins are important in binary cell-fate decisions and inhibiting differentiation in many developmental systems, and aberrant Notch signaling is associated with tumorigenesis. The role of Notch signaling in mammalian skin is less well characterized and is mainly based on in vitro studies, which suggest that Notch signaling induces differentiation in mammalian skin. Conventional gene targeting is not applicable to establishing the role of Notch receptors or ligands in the skin because Notch1-/- embryos die during gestation. Therefore, we used a tissue-specific inducible gene-targeting approach to study the physiological role of the Notch1 receptor in the mouse epidermis and the corneal epithelium of adult mice. Unexpectedly, ablation of Notch1 results in epidermal and corneal hyperplasia followed by the development of skin tumors and facilitated chemical-induced skin carcinogenesis. Notch1 deficiency in skin and in primary keratinocytes results in increased and sustained expression of Gli2, causing the development of basal-cell carcinoma-like tumors. Furthermore, Notch1 inactivation in the epidermis results in derepressed beta-catenin signaling in cells that should normally undergo differentiation. Enhanced beta-catenin signaling can be reversed by re-introduction of a dominant active form of the Notch1 receptor. This leads to a reduction in the signaling-competent pool of beta-catenin, indicating that Notch1 can inhibit beta-catenin-mediated signaling. Our results indicate that Notch1 functions as a tumor-suppressor gene in mammalian skin.

  7. Thermally Actuated Hydraulic Pumps

    Science.gov (United States)

    Jones, Jack; Ross, Ronald; Chao, Yi

    2008-01-01

    Thermally actuated hydraulic pumps have been proposed for diverse applications in which direct electrical or mechanical actuation is undesirable and the relative slowness of thermal actuation can be tolerated. The proposed pumps would not contain any sliding (wearing) parts in their compressors and, hence, could have long operational lifetimes. The basic principle of a pump according to the proposal is to utilize the thermal expansion and contraction of a wax or other phase-change material in contact with a hydraulic fluid in a rigid chamber. Heating the chamber and its contents from below to above the melting temperature of the phase-change material would cause the material to expand significantly, thus causing a substantial increase in hydraulic pressure and/or a substantial displacement of hydraulic fluid out of the chamber. Similarly, cooling the chamber and its contents from above to below the melting temperature of the phase-change material would cause the material to contract significantly, thus causing a substantial decrease in hydraulic pressure and/or a substantial displacement of hydraulic fluid into the chamber. The displacement of the hydraulic fluid could be used to drive a piston. The figure illustrates a simple example of a hydraulic jack driven by a thermally actuated hydraulic pump. The pump chamber would be a cylinder containing encapsulated wax pellets and containing radial fins to facilitate transfer of heat to and from the wax. The plastic encapsulation would serve as an oil/wax barrier and the remaining interior space could be filled with hydraulic oil. A filter would retain the encapsulated wax particles in the pump chamber while allowing the hydraulic oil to flow into and out of the chamber. In one important class of potential applications, thermally actuated hydraulic pumps, exploiting vertical ocean temperature gradients for heating and cooling as needed, would be used to vary hydraulic pressures to control buoyancy in undersea research

  8. Notched delta, phenotype, and Angelman syndrome.

    Science.gov (United States)

    Korff, Christian M; Kelley, Kent R; Nordli, Douglas R

    2005-08-01

    The notched delta pattern is one of the characteristic EEG features found in Angelman syndrome patients. The purpose of this study was to evaluate the possibility of using the notched delta pattern as a detection tool for Angelman syndrome patients by analyzing its frequency in a tertiary care pediatric center, its specificity for Angelman syndrome, and the age at which it was observed. The authors performed a retrospective review of the video-EEG recordings of all the patients who had either the notched delta pattern or a phenotype consistent with Angelman syndrome. The notched delta was observed in 1.1% of all the EEGs performed. Its specificity for Angelman syndrome was evaluated at 38%. The youngest age at which it was noted was 14 months. The results indicate that the notched delta pattern is relatively rare, but more frequent than expected, and is easily recognizable. The pattern was observed not only in Angelman syndrome patients, but also in children with a spectrum of conditions wider than reported. It is a powerful detection tool for Angelman syndrome when correlated to a suggestive phenotype, and the association of these features should raise suspicion for Angelman syndrome in both infants and adults.

  9. Hazards and Safeguards of High Pressure Hydraulic Fatigue Testing

    Science.gov (United States)

    1990-07-01

    rew e I&64aN neem mde tliF by block mumber) The creation and transfer of hydraulic pressure at the 690-MPa (100,000-psi) level is in itself hazardous...than alloy steel, we have found that it is more notch sensitive to fatigue and drastically degrades with small constituent variations. To avoid this...I ATTN: SMCWV-PP DIRECTOR, PRODUCT ASSURANCE DIRECTORATE 1 ATTN: SMCWV-QA NOTE: PLEASE NOTIFY DIRECTOR, BENET LABORATORIES, ATTN: SMCAR-CCB-TL, OF ANY

  10. Notch in mammary gland development and breast cancer.

    Science.gov (United States)

    Politi, Katerina; Feirt, Nikki; Kitajewski, Jan

    2004-10-01

    Notch signaling has been implicated in many processes including cell fate determination and oncogenesis. In mice, the Notch1 and Notch4 genes are both targets for insertion and rearrangement by the mouse mammary tumor virus and these mutations promote epithelial mammary tumorigenesis. Moreover, expression of a constitutively active form of Notch4 in mammary epithelial cells inhibits epithelial differentiation and leads to tumor formation in this organ. These data implicate the Notch pathway in breast tumorigenesis and provide the foundation for future experiments that will aid in our understanding of the role of Notch in human breast cancer development. Here, we review studies of mammary tumorigenesis induced by Notch in mouse and in vitro culture models providing evidence that Notch activation is a causal factor in human breast cancer.

  11. Emerin suppresses Notch signaling by restricting the Notch intracellular domain to the nuclear membrane.

    Science.gov (United States)

    Lee, Byongsun; Lee, Tae-Hee; Shim, Jaekyung

    2017-02-01

    Emerin is an inner nuclear membrane protein that is involved in maintaining the mechanical integrity of the nuclear membrane. Increasing evidence supports the involvement of emerin in the regulation of gene expression; however, its precise function remains to be elucidated. Here, we show that emerin downregulated genes downstream of Notch signaling, which are activated exclusively by the Notch intracellular domain (NICD). Deletion mutant experiments revealed that the transmembrane domain of emerin is important for the inhibition of Notch signaling. Emerin interacted directly and colocalized with the NICD at the nuclear membrane. Emerin knockdown induced the phosphorylation of ERK and AKT, increased endogenous Notch signaling, and inhibited hydrogen peroxide-induced apoptosis in HeLa cells. Notably, the downregulation of barrier-to-autointegration factor (BAF) or lamin A/C increased Notch signaling by inducing the release of emerin into the cytosol, implying that nuclear membrane-bound emerin acts as an endogenous inhibitor of Notch signaling. Taken together, our results indicate that emerin negatively regulates Notch signaling by promoting the retention of the NICD at the nuclear membrane. This mechanism could constitute a new therapeutic target for the treatment of emerin-related diseases.

  12. EXPERIMENTAL INVESTIGATIONS OF CAVITATION EFFECTS ON FLOW CHARACTERISTICS OF SMALL ORIFICES AND VALVES IN WATER HYDRAULICS

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The flow characteristics and cavitation effects of water passing through small sharp-edged cylindrical orificesand valves of different shapes in water hydraulics are investigated. The test results using orifices with different aspect ra-tios and different diameters show that the flow coefficients in the case of non-cavitating flow are larger than that of row inthe case of cavitation occurrence. The flow coefficients of flow with cavitation initially decrease as Reynolds number in-creases and ultimately tend to be of constant values close to contraction coefficient. Large aspect ratio has an effect ofsuppressing cavitation. The experimental results about disc valves illustrate that the valves with sharp edge at large open-ing are less affected by cavitation than that at small opening. Throttle with triangle notch has better anti-cavitation abilitythan that with square notch. The flowrate of the throttle with square notch is significantly affected by the flow direction orthe flow passage shape.

  13. Vibration of hydraulic machinery

    CERN Document Server

    Wu, Yulin; Liu, Shuhong; Dou, Hua-Shu; Qian, Zhongdong

    2013-01-01

    Vibration of Hydraulic Machinery deals with the vibration problem which has significant influence on the safety and reliable operation of hydraulic machinery. It provides new achievements and the latest developments in these areas, even in the basic areas of this subject. The present book covers the fundamentals of mechanical vibration and rotordynamics as well as their main numerical models and analysis methods for the vibration prediction. The mechanical and hydraulic excitations to the vibration are analyzed, and the pressure fluctuations induced by the unsteady turbulent flow is predicted in order to obtain the unsteady loads. This book also discusses the loads, constraint conditions and the elastic and damping characters of the mechanical system, the structure dynamic analysis, the rotor dynamic analysis and the system instability of hydraulic machines, including the illustration of monitoring system for the instability and the vibration in hydraulic units. All the problems are necessary for vibration pr...

  14. Handbook of hydraulic fluid technology

    CERN Document Server

    Totten, George E

    2011-01-01

    ""The Handbook of Hydraulic Fluid Technology"" serves as the foremost resource for designing hydraulic systems and for selecting hydraulic fluids used in engineering applications. Featuring new illustrations, data tables, as well as practical examples, this second edition is updated with essential information on the latest hydraulic fluids and testing methods. The detailed text facilitates unparalleled understanding of the total hydraulic system, including important hardware, fluid properties, and hydraulic lubricants. Written by worldwide experts, the book also offers a rigorous overview of h

  15. New band-notched UWB antenna

    Institute of Scientific and Technical Information of China (English)

    HE Xiao-xiang; DENG Hong-wei

    2009-01-01

    A simple and compact ultra wideband (UWB) printed monopole antenna with band-notched performance is proposed in this paper. The antenna is partially grounded so that the Q value is depressed and the impedance bandwidth is broadened. A small strip bar is loaded on each arm of the similar U-shaped radiator. The impedance bandwidth of the antenna overlap with IEEE 802.11a is rejected consequently. The geometry parameters of the antenna are investigated and optimized with HFSS. The measured bandwidth of the proposed antenna occupies about 7.89 GHz covering from 3.05 GHz to 10.94 GHz with expected notched band from 4.96 GHz to 5.98 GHz. A quasi-omnidirectional and quasi-symmetrical radiation pattern in the whole band is also obtained. As a result, a UWB wireless communication system can be simplified with the band-notched UWB antenna presented.

  16. Comparative analysis of Notch1 and Notch2 binding sites in the genome of BxPC3 pancreatic cancer cells

    Science.gov (United States)

    Liu, Hao; Zhou, Ping; Lan, Hong; Chen, Jia; Zhang, Yu-xiang

    2017-01-01

    Notch signaling plays a key role in the development of pancreatic cancer. Among the four identified Notch receptors, Notch1 and Notch2 share the highest homology. Notch1 has been reported to be an oncogene but some reports indicate that Notch2, not Notch1, plays a key role in pancreatic carcinogenesis. As both are transcription factors, examination of their genomic binding sites might reveal interesting functional differences between them. Notch proteins do not have DNA-binding domain. In the canonical Notch signaling pathway, ligand binding induces the release and nuclear translocation of Notch receptor intracellular domains (NICDs), which then interact with the transcription factor CSL, resulting in subsequent activation of the canonical Notch target genes. We investigated the binding site profiles of Notch1and Notch2 in the BxPC3 genome using CHIP-Seq and bioinfomatics. We found that Notch1, Notch2 and CSL generally bound to different target genes. We also found that only a small subset of Notch1 and Notch2 binding sites overlap with that of CSL, but about half of the CSL binding overlap with that of Notch1 or Notch2, indicating most Notch signaling activities are CSL-independent.

  17. Comparative analysis of Notch1 and Notch2 binding sites in the genome of BxPC3 pancreatic cancer cells.

    Science.gov (United States)

    Liu, Hao; Zhou, Ping; Lan, Hong; Chen, Jia; Zhang, Yu-Xiang

    2017-01-01

    Notch signaling plays a key role in the development of pancreatic cancer. Among the four identified Notch receptors, Notch1 and Notch2 share the highest homology. Notch1 has been reported to be an oncogene but some reports indicate that Notch2, not Notch1, plays a key role in pancreatic carcinogenesis. As both are transcription factors, examination of their genomic binding sites might reveal interesting functional differences between them. Notch proteins do not have DNA-binding domain. In the canonical Notch signaling pathway, ligand binding induces the release and nuclear translocation of Notch receptor intracellular domains (NICDs), which then interact with the transcription factor CSL, resulting in subsequent activation of the canonical Notch target genes. We investigated the binding site profiles of Notch1and Notch2 in the BxPC3 genome using CHIP-Seq and bioinfomatics. We found that Notch1, Notch2 and CSL generally bound to different target genes. We also found that only a small subset of Notch1 and Notch2 binding sites overlap with that of CSL, but about half of the CSL binding overlap with that of Notch1 or Notch2, indicating most Notch signaling activities are CSL-independent.

  18. Activation of the NOTCH pathway in head and neck cancer.

    Science.gov (United States)

    Sun, Wenyue; Gaykalova, Daria A; Ochs, Michael F; Mambo, Elizabeth; Arnaoutakis, Demetri; Liu, Yan; Loyo, Myriam; Agrawal, Nishant; Howard, Jason; Li, Ryan; Ahn, Sun; Fertig, Elana; Sidransky, David; Houghton, Jeffery; Buddavarapu, Kalyan; Sanford, Tiffany; Choudhary, Ashish; Darden, Will; Adai, Alex; Latham, Gary; Bishop, Justin; Sharma, Rajni; Westra, William H; Hennessey, Patrick; Chung, Christine H; Califano, Joseph A

    2014-02-15

    NOTCH1 mutations have been reported to occur in 10% to 15% of head and neck squamous cell carcinomas (HNSCC). To determine the significance of these mutations, we embarked upon a comprehensive study of NOTCH signaling in a cohort of 44 HNSCC tumors and 25 normal mucosal samples through a set of expression, copy number, methylation, and mutation analyses. Copy number increases were identified in NOTCH pathway genes, including the NOTCH ligand JAG1. Gene set analysis defined a differential expression of the NOTCH signaling pathway in HNSCC relative to normal tissues. Analysis of individual pathway-related genes revealed overexpression of ligands JAG1 and JAG2 and receptor NOTCH3. In 32% of the HNSCC examined, activation of the downstream NOTCH effectors HES1/HEY1 was documented. Notably, exomic sequencing identified 5 novel inactivating NOTCH1 mutations in 4 of the 37 tumors analyzed, with none of these tumors exhibiting HES1/HEY1 overexpression. Our results revealed a bimodal pattern of NOTCH pathway alterations in HNSCC, with a smaller subset exhibiting inactivating NOTCH1 receptor mutations but a larger subset exhibiting other NOTCH1 pathway alterations, including increases in expression or gene copy number of the receptor or ligands as well as downstream pathway activation. Our results imply that therapies that target the NOTCH pathway may be more widely suitable for HNSCC treatment than appreciated currently.

  19. How Notch and Wnt make T-cells tick

    NARCIS (Netherlands)

    Helbig, C.

    2013-01-01

    This dissertation shows that the ancient Wnt and Notch signaling modules have been coopted by the immune system to direct T-cell responses. Notch has turned out to be particularly dedicated to induction of effector cell differentiation and function. Lack of Notch activation may predispose cells to l

  20. Notch-strengthening in two-dimensional foams

    NARCIS (Netherlands)

    Onck, P.R.

    2001-01-01

    Metallic foams show notch-strengthening behavior when analyzing double-edge notched specimen in compression and tension. A discrete microstructural model has been used to simulate the effect of notch depth and specimen size on the net-section-strength. The non-uniform deformation behavior is analyze

  1. Solution notches, earthquakes, and sea level, Haiti

    Science.gov (United States)

    Schiffman, C. R.; Mildor, B. S.; Bilham, R. G.

    2010-12-01

    Shortly after the 12 January 2010 Haiti earthquake, we installed an array of five tide gauges to determine sea level and its variability in the region of uplifted corals on the coast SW of Leogane, Haiti, that had been uplift ≤30 cm during the earthquake. Each gauge consists of a pressure transducer bolted 50-80 cm below mean sea level, which samples the difference between atmospheric pressure and sea pressure every 10 minutes. The data are transmitted via the Iridium satellite and are publically available with a latency of 10 minutes to 2 hours. The measurements reveal a maximum tidal range of ≈50 cm with 2-4 week oscillations in mean sea level of several cm. Sea slope, revealed by differences between adjacent gauges, varies 2-5 cm per 10 km at periods of 2-5 weeks, which imposes a disappointing limit to the utility of the gauges in estimating post seismic vertical motions. A parallel study of the form and elevation of coastal notches and mushroom rocks (rocks notched on all sides, hence forming a mushroom shape), along the coast west of Petit Goave suggests that these notches may provide an uplift history of the region over the past several hundreds of years. Notch sections in two areas were contoured, digitized, and compared to mean sea level. The notches mimic the histogram of sea level, suggesting that they are formed by dissolution by acidic surface waters. Notches formed two distinct levels, one approximately 58 cm above mean sea level, and the other approximately 157 cm above mean sea level. Several landslide blocks fell into the sea during the 2010 earthquake, and we anticipate these are destined for conversion to future mushroom rocks. Surfaces have been prepared on these blocks to study the rate of notch formation in situ, and samples are being subjected to acid corrosion in laboratory conditions, with the hope that the depth of notches may provide an estimate of the time of fall of previous rocks to help constrain the earthquake history of this area

  2. Role of Notch signaling in the mammalian heart

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, X.L.; Liu, J.C. [Department of Cardiac Surgery, The First Affiliated Hospital, Nanchang University, Donghu District, Nanchang, Jiangxi (China)

    2013-12-12

    Notch signaling is an evolutionarily ancient, highly conserved pathway important for deciding cell fate, cellular development, differentiation, proliferation, apoptosis, adhesion, and epithelial-to-mesenchymal transition. Notch signaling is also critical in mammalian cardiogenesis, as mutations in this signaling pathway are linked to human congenital heart disease. Furthermore, Notch signaling can repair myocardial injury by promoting myocardial regeneration, protecting ischemic myocardium, inducing angiogenesis, and negatively regulating cardiac fibroblast-myofibroblast transformation. This review provides an update on the known roles of Notch signaling in the mammalian heart. The goal is to assist in developing strategies to influence Notch signaling and optimize myocardial injury repair.

  3. Analysis list: Notch1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Notch1 Blood + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Notch1.1.t...sv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Notch1.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Notch1....10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Notch1.Blood.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Blood.gml ...

  4. In vivo analysis of the Notch receptor S1 cleavage.

    Directory of Open Access Journals (Sweden)

    Robert J Lake

    Full Text Available A ligand-independent cleavage (S1 in the extracellular domain of the mammalian Notch receptor results in what is considered to be the canonical heterodimeric form of Notch on the cell surface. The in vivo consequences and significance of this cleavage on Drosophila Notch signaling remain unclear and contradictory. We determined the cleavage site in Drosophila and examined its in vivo function by a transgenic analysis of receptors that cannot be cleaved. Our results demonstrate a correlation between loss of cleavage and loss of in vivo function of the Notch receptor, supporting the notion that S1 cleavage is an in vivo mechanism of Notch signal control.

  5. Jet Quenching via Jet Collimation

    CERN Document Server

    Casalderrey-Solana, Jorge; Wiedemann, Urs Achim

    2011-01-01

    The ATLAS Collaboration recently reported strong modifications of dijet properties in heavy ion collisions. In this work, we discuss to what extent these first data constrain already the microscopic mechanism underlying jet quenching. Simple kinematic arguments lead us to identify a frequency collimation mechanism via which the medium efficiently trims away the soft components of the jet parton shower. Through this mechanism, the observed dijet asymmetry can be accomodated with values of $\\hat{q}\\, L$ that lie in the expected order of magnitude.

  6. Compact microstrip bandpass filter with tunable notch

    DEFF Research Database (Denmark)

    Christensen, Silas; Zhurbenko, Vitaliy; Johansen, Tom Keinicke

    2014-01-01

    Two different designs combining a bandpass and a notch filter are developed to operate in the receiving band from 350–470 MHz. The bandpass filter is designed from a simple structure, by use of only four short circuited stubs and a half wavelength transmission line connecting the stubs. The tunable...

  7. Notch pathway is dispensable for adipocyte specification.

    Science.gov (United States)

    Nichols, Amy M; Pan, Yonghua; Herreman, An; Hadland, Brandon K; De Strooper, Bart; Kopan, Raphael; Huppert, Stacey S

    2004-09-01

    In the past decade we have witnessed an epidemic of obesity in developed countries. Therefore, understanding the mechanisms involved in regulation of body weight is becoming an increasingly important goal shared by the public and the scientific community. The key to fat deposition is the adipocyte, a specialized cell that plays a critical role in energy balance and appetite regulation. Much of our knowledge of adipogenesis comes from studies using preadipocytic cell lines that have provided important information regarding molecular control of adipocyte differentiation. However, they fall short of revealing how naive cells acquire competence for adipogenesis. Studies in preadipocytes indicate that the Notch pathway plays a role in regulating adipogenesis (Garces et al.: J Biol Chem 272:29729-29734, 1997). Given the known biological functions of Notch in mediating cell fate decisions (Artavanis-Tsakonas et al.: Science 284:770-776, 1999), we wished to test the hypothesis that the Notch pathway is required for this cellular program by examining adipogenesis in several genetic loss-of-function models that encompass the entire pathway. We conclude that the "canonical" Notch signaling pathway is dispensable for adipocyte specification and differentiation from either mesenchymal or epithelial progenitors.

  8. Notch and VEGF Interactions in Breast Cancer

    Science.gov (United States)

    2006-04-01

    induces VEGFR-3 expression in cultured endothelial cells, we want to test whether blocking Notch activity suppressed tumor growth and pathological...Y.W., Shawber, C., Paty, P. and Barany , F. (2005) Accurate multiplexed detection of methylation status in CpG islands of candidate genes using a

  9. Notch3 interactome analysis identified WWP2 as a negative regulator of Notch3 signaling in ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Jin-Gyoung Jung

    2014-10-01

    Full Text Available The Notch3 signaling pathway is thought to play a critical role in cancer development, as evidenced by the Notch3 amplification and rearrangement observed in human cancers. However, the molecular mechanism by which Notch3 signaling contributes to tumorigenesis is largely unknown. In an effort to identify the molecular modulators of the Notch3 signaling pathway, we screened for Notch3-intracellular domain (N3-ICD interacting proteins using a human proteome microarray. Pathway analysis of the Notch3 interactome demonstrated that ubiquitin C was the molecular hub of the top functional network, suggesting the involvement of ubiquitination in modulating Notch3 signaling. Thereby, we focused on functional characterization of an E3 ubiquitin-protein ligase, WWP2, a top candidate in the Notch3 interactome list. Co-immunoprecipitation experiments showed that WWP2 interacted with N3-ICD but not with intracellular domains from other Notch receptors. Wild-type WWP2 but not ligase-deficient mutant WWP2 increases mono-ubiquitination of the membrane-tethered Notch3 fragment, therefore attenuating Notch3 pathway activity in cancer cells and leading to cell cycle arrest. The mono-ubiquitination by WWP2 may target an endosomal/lysosomal degradation fate for Notch3 as suggested by the fact that the process could be suppressed by the endosomal/lysosomal inhibitor. Analysis of The Cancer Genome Atlas dataset showed that the majority of ovarian carcinomas harbored homozygous or heterozygous deletions in WWP2 locus, and there was an inverse correlation in the expression levels between WWP2 and Notch3 in ovarian carcinomas. Furthermore, ectopic expression of WWP2 decreased tumor development in a mouse xenograft model and suppressed the Notch3-induced phenotypes including increase in cancer stem cell-like cell population and platinum resistance. Taken together, our results provide evidence that WWP2 serves as a tumor suppressor by negatively regulating Notch3 signaling

  10. Inhibitory role of Notch1 in calcific aortic valve disease.

    Directory of Open Access Journals (Sweden)

    Asha Acharya

    Full Text Available Aortic valve calcification is the most common form of valvular heart disease, but the mechanisms of calcific aortic valve disease (CAVD are unknown. NOTCH1 mutations are associated with aortic valve malformations and adult-onset calcification in families with inherited disease. The Notch signaling pathway is critical for multiple cell differentiation processes, but its role in the development of CAVD is not well understood. The aim of this study was to investigate the molecular changes that occur with inhibition of Notch signaling in the aortic valve. Notch signaling pathway members are expressed in adult aortic valve cusps, and examination of diseased human aortic valves revealed decreased expression of NOTCH1 in areas of calcium deposition. To identify downstream mediators of Notch1, we examined gene expression changes that occur with chemical inhibition of Notch signaling in rat aortic valve interstitial cells (AVICs. We found significant downregulation of Sox9 along with several cartilage-specific genes that were direct targets of the transcription factor, Sox9. Loss of Sox9 expression has been published to be associated with aortic valve calcification. Utilizing an in vitro porcine aortic valve calcification model system, inhibition of Notch activity resulted in accelerated calcification while stimulation of Notch signaling attenuated the calcific process. Finally, the addition of Sox9 was able to prevent the calcification of porcine AVICs that occurs with Notch inhibition. In conclusion, loss of Notch signaling contributes to aortic valve calcification via a Sox9-dependent mechanism.

  11. Identification of novel Notch target genes in T cell leukaemia

    Directory of Open Access Journals (Sweden)

    Warrander Fiona

    2009-06-01

    Full Text Available Abstract Background Dysregulated Notch signalling is believed to play an important role in the development and maintenance of T cell leukaemia. At a cellular level, Notch signalling promotes proliferation and inhibits apoptosis of T cell acute lymphoblastic leukaemia (T-ALL cells. In this study we aimed to identify novel transcriptional targets of Notch signalling in the T-ALL cell line, Jurkat. Results RNA was prepared from Jurkat cells retrovirally transduced with an empty vector (GFP-alone or vectors containing constitutively active forms of Notch (N1ΔE or N3ΔE, and used for Affymetrix microarray analysis. A subset of genes found to be regulated by Notch was chosen for real-time PCR validation and in some cases, validation at the protein level, using several Notch-transduced T-ALL and non-T-ALL leukaemic cell lines. As expected, several known transcriptional target of Notch, such as HES1 and Deltex, were found to be overexpressed in Notch-transduced cells, however, many novel transcriptional targets of Notch signalling were identified using this approach. These included the T cell costimulatory molecule CD28, the anti-apoptotic protein GIMAP5, and inhibitor of DNA binding 1 (1D1. Conclusion The identification of such downstream Notch target genes provides insights into the mechanisms of Notch function in T cell leukaemia, and may help identify novel therapeutic targets in this disease.

  12. FEMA DFIRM Hydraulic Structures

    Data.gov (United States)

    Minnesota Department of Natural Resources — This layer and accompanying attribute table is required whenever hydraulic structures are shown in the flood profile. It is also required if levees are shown on the...

  13. Water Hydraulic Systems

    DEFF Research Database (Denmark)

    Conrad, Finn

    2005-01-01

    The paper presents research results using IT-Tools for CAD and dynamic modelling, simulation, analysis, and design of water hydraulic actuators for motion control of machines, lifts, cranes and robots. Matlab/Simulink and CATIA are used as IT-Tools. The contributions include results from on......-going research projects on fluid power and mechatronics based on tap water hydraulic servovalves and linear servo actuators and rotary vane actuators for motion control and power transmission. Development and design a novel water hydraulic rotary vane actuator for robot manipulators. Proposed mathematical...... modelling, control and simulation of a water hydraulic rotary vane actuator applied to power and control a two-links manipulator and evaluate performance. The results include engineering design and test of the proposed simulation models compared with IHA Tampere University’s presentation of research...

  14. Constant-Pressure Hydraulic Pump

    Science.gov (United States)

    Galloway, C. W.

    1982-01-01

    Constant output pressure in gas-driven hydraulic pump would be assured in new design for gas-to-hydraulic power converter. With a force-multiplying ring attached to gas piston, expanding gas would apply constant force on hydraulic piston even though gas pressure drops. As a result, pressure of hydraulic fluid remains steady, and power output of the pump does not vary.

  15. Targeting Notch degradation system provides promise for breast cancer therapeutics.

    Science.gov (United States)

    Liu, Jing; Shen, Jia-Xin; Wen, Xiao-Fen; Guo, Yu-Xian; Zhang, Guo-Jun

    2016-08-01

    Notch receptor signaling pathways play an important role, not only in normal breast development but also in breast cancer development and progression. As a group of ligand-induced proteins, different subtypes of mammalian Notch (Notch1-4) are sensitive to subtle changes in protein levels. Thus, a clear understanding of mechanisms of Notch protein turnover is essential for understanding normal and pathological mechanisms of Notch functions. It has been suggested that there is a close relationship between the carcinogenesis and the dysregulation of Notch degradation. However, this relationship remains mostly undefined in the context of breast cancer, as protein degradation is mediated by numerous signaling pathways as well as certain molecule modulators (activators/inhibitors). In this review, we summarize the published data regarding the regulation of Notch family member degradation in breast cancer, while emphasizing areas that are likely to provide new therapeutic modalities for mechanism-based anti-cancer drugs.

  16. Dichotomy of Solar Coronal Jets: Standard Jets and Blowout Jets

    Science.gov (United States)

    Moore, R. L.; Cirtain, J. W.; Sterling, A. C.; Falconer, D. A.

    2010-01-01

    By examining many X-ray jets in Hinode/XRT coronal X-ray movies of the polar coronal holes, we found that there is a dichotomy of polar X-ray jets. About two thirds fit the standard reconnection picture for coronal jets, and about one third are another type. We present observations indicating that the non-standard jets are counterparts of erupting-loop H alpha macrospicules, jets in which the jet-base magnetic arch undergoes a miniature version of the blowout eruptions that produce major CMEs. From the coronal X-ray movies we present in detail two typical standard X-ray jets and two typical blowout X-ray jets that were also caught in He II 304 Angstrom snapshots from STEREO/EUVI. The distinguishing features of blowout X-ray jets are (1) X-ray brightening inside the base arch in addition to the outside bright point that standard jets have, (2) blowout eruption of the base arch's core field, often carrying a filament of cool (T 10(exp 4) - 10(exp 5) K) plasma, and (3) an extra jet-spire strand rooted close to the bright point. We present cartoons showing how reconnection during blowout eruption of the base arch could produce the observed features of blowout X-ray jets. We infer that (1) the standard-jet/blowout-jet dichotomy of coronal jets results from the dichotomy of base arches that do not have and base arches that do have enough shear and twist to erupt open, and (2) there is a large class of spicules that are standard jets and a comparably large class of spicules that are blowout jets.

  17. Kilowatt Isotope Power System: component test report for the ground demonstration system jet condenser orifice performance. 77-KIPS-103

    Energy Technology Data Exchange (ETDEWEB)

    Brainard, E.L.

    1977-11-08

    The purpose of these tests was to determine which orifice elements achieved satisfactory hydraulic and thermal performance prior to their incorporation into the Jet Condenser Assembly. Requirements were as set forth within the Kilowatt Isotope Power System (KIPS) Component Test Procedure number 414 for the Jet Condenser Orifice Performance testing. The results of the performance testing conducted on the Jet Condenser Orifices are presented. Part Number 720841 Jet Condenser Orifice Nozzle successfully completed the orifice screening tests.

  18. Notch Regulates Macrophage-Mediated Inflammation in Diabetic Wound Healing.

    Science.gov (United States)

    Kimball, Andrew S; Joshi, Amrita D; Boniakowski, Anna E; Schaller, Matthew; Chung, Jooho; Allen, Ronald; Bermick, Jennifer; Carson, William F; Henke, Peter K; Maillard, Ivan; Kunkel, Steve L; Gallagher, Katherine A

    2017-01-01

    Macrophages are essential immune cells necessary for regulated inflammation during wound healing. Recent studies have identified that Notch plays a role in macrophage-mediated inflammation. Thus, we investigated the role of Notch signaling on wound macrophage phenotype and function during normal and diabetic wound healing. We found that Notch receptor and ligand expression are dynamic in wound macrophages during normal healing. Mice with a myeloid-specific Notch signaling defect (DNMAML(floxed)Lyz2(Cre+) ) demonstrated delayed early healing (days 1-3) and wound macrophages had decreased inflammatory gene expression. In our physiologic murine model of type 2 diabetes (T2D), Notch receptor expression was significantly increased in wound macrophages on day 6, following the initial inflammatory phase of wound healing, corresponding to increased inflammatory cytokine expression. This increase in Notch1 and Notch2 was also observed in human monocytes from patients with T2D. Further, in prediabetic mice with a genetic Notch signaling defect (DNMAML(floxed)Lyz2(Cre+) on a high-fat diet), improved wound healing was seen at late time points (days 6-7). These findings suggest that Notch is critical for the early inflammatory phase of wound healing and directs production of macrophage-dependent inflammatory mediators. These results identify that canonical Notch signaling is important in directing macrophage function in wound repair and define a translational target for the treatment of non-healing diabetic wounds.

  19. Notch Regulates Macrophage-Mediated Inflammation in Diabetic Wound Healing

    Directory of Open Access Journals (Sweden)

    Andrew S. Kimball

    2017-06-01

    Full Text Available Macrophages are essential immune cells necessary for regulated inflammation during wound healing. Recent studies have identified that Notch plays a role in macrophage-mediated inflammation. Thus, we investigated the role of Notch signaling on wound macrophage phenotype and function during normal and diabetic wound healing. We found that Notch receptor and ligand expression are dynamic in wound macrophages during normal healing. Mice with a myeloid-specific Notch signaling defect (DNMAMLfloxedLyz2Cre+ demonstrated delayed early healing (days 1–3 and wound macrophages had decreased inflammatory gene expression. In our physiologic murine model of type 2 diabetes (T2D, Notch receptor expression was significantly increased in wound macrophages on day 6, following the initial inflammatory phase of wound healing, corresponding to increased inflammatory cytokine expression. This increase in Notch1 and Notch2 was also observed in human monocytes from patients with T2D. Further, in prediabetic mice with a genetic Notch signaling defect (DNMAMLfloxedLyz2Cre+ on a high-fat diet, improved wound healing was seen at late time points (days 6–7. These findings suggest that Notch is critical for the early inflammatory phase of wound healing and directs production of macrophage-dependent inflammatory mediators. These results identify that canonical Notch signaling is important in directing macrophage function in wound repair and define a translational target for the treatment of non-healing diabetic wounds.

  20. Dynamics of notch expression during murine prostate development and tumorigenesis.

    Science.gov (United States)

    Shou, J; Ross, S; Koeppen, H; de Sauvage, F J; Gao, W Q

    2001-10-01

    Notch signaling has been widely demonstrated to be responsible for cell fate determination during normal development and implicated in human T-cell leukemia and mouse mammary carcinomas. Here we show that Notch signaling may be involved in prostatic development and cancer cell growth. In situ hybridization and reverse transcription-PCR analyses revealed that Notch1 was expressed in prostate epithelial cells during normal development and in prostate cancer cells. Characterization of Notch1-green fluorescent protein transgenic mice, in which the expression of reporter green fluorescent protein is under the control of the Notch1 promoter, indicated that Notch1-expressing cells were associated with the basal epithelial cell population in the prostate. Examination of the transgenic adenocarcinoma of the mouse prostate showed that expression of Notch1 was elevated in malignant prostatic epithelial cells of primary and metastatic tumors. Expression of Notch ligands, however, was low or undetectable in cultured prostate cancer cells or in malignant prostatic epithelial cells in transgenic adenocarcinoma of the mouse prostate. Furthermore, overexpression of a constitutively active form of Notch1 inhibited the proliferation of various prostate cancer cells, including DU145, LNCaP, and PC3 cells. Taken together, our data indicate for the first time that Notch signaling may play a role in murine prostatic development and tumorigenesis.

  1. Notch as a Driver of Gastric Epithelial Cell Proliferation.

    Science.gov (United States)

    Demitrack, Elise S; Samuelson, Linda C

    2017-05-01

    The gastric epithelium is sustained by a population of stem cells that replenish the various mature epithelial lineages throughout adulthood. Regulation of stem and progenitor cell proliferation occurs via basic developmental signaling pathways, including the Notch pathway, which recently was described to promote gastric stem cell proliferation in both mice and human beings. Current cancer theory proposes that adult stem cells that maintain gastrointestinal tissues accumulate mutations that promote cancerous growth, and that basic signaling pathways, such as Notch, which stimulate stem cell proliferation, can promote tumorigenesis. Accordingly, constitutive Notch activation leads to unchecked cellular proliferation and gastric tumors in genetic mouse models. Furthermore, there is emerging evidence suggesting that the Notch pathway may be activated in some human gastric cancers, supporting a potential role for Notch in gastric tumorigenesis. In this review, we first summarize the current understanding of gastric stem cells defined by genetic mouse studies, followed by discussion of the literature regarding Notch pathway regulation of gastric stem cell function in the mouse and human beings. Notch action to maintain gastric epithelial cell homeostasis and the cellular consequences of dysregulated signaling to promote tumorigenesis are discussed, including studies associating Notch activation with human gastric cancer. Finally, we compare and contrast Notch function in the stomach with other gastrointestinal tissues, including the intestine, to highlight the sensitivity of the stomach to Notch-induced tumors.

  2. Prognostic values of Notch receptors in breast cancer.

    Science.gov (United States)

    Xu, Junming; Song, Fangbin; Jin, Tao; Qin, Jun; Wu, Junyi; Wang, Min; Wang, Ye; Liu, Jun

    2016-02-01

    Notch receptors are frequently deregulated in several human malignancies including human breast cancer. Activation of Notch has been reported to cause mammary carcinomas in mice. However, the prognostic value of individual Notch receptors in breast cancer (BC) patients remains elusive. In the current study, we investigated the prognostic value of Notch receptors in human BC patients. More specifically, we investigated the prognostic value of four Notch receptors in breast cancer patients through "the Kaplan-Meier plotter" (KM plotter) database, in which updated gene expression data and survival information are from a total of 3554 breast cancer patients. Our results showed that Notch1 messenger RNA (mRNA) high expression was correlated to worsen overall survival (OS) in PgR-negative BC patients. Notch2, Notch3, and Notch4 mRNA high expressions were found to be correlated to better OS for all breast cancer patients. Notch2 was also found to be correlated to better OS in lymph node-negative breast cancer patients and HER2-positive breast cancer patients. These results will be useful for better understanding of the heterogeneity and complexity in the molecular biology of breast cancer and for developing tools to more accurately predict their prognosis and design their customized treatment strategies.

  3. Trend of hydraulic units

    Energy Technology Data Exchange (ETDEWEB)

    Deshimaru, Jun' ichi

    1988-11-01

    The gear, vane and piston pumps occupy a more then 90% share in the hydraulic pumps. Comparatively large pumps are mainly variable delivery piston pumps. The piston pumps are comparatively high in output density (output per unit weight), indicating the hydraulic pump in performance, and tend to become higher and higher in it. Though they are mainly 210 to 350kgf/cm/sup 2/ in rated pressure, some of them come to surpass 400kgf/cm/sup 3/ in it. While the progress in computation also requires the high speed operation, high accuracy and other severe conditions for the hydraulic units, which accordingly and increasingly intensify the requirement for hydraulic oil in abrasion resistibility, oxidation stability and response characteristics. While cavitation comes to easily occur, which considerably and disadvantageously influences hydraulic oil in life through degradation, noise level and respondingness. From now on, the development of high performance oil and study of mechanical structure are important. 19 references, 9 figures, 2 tables.

  4. Hydraulics of a multiple slit-type energy dissipater

    Institute of Scientific and Technical Information of China (English)

    吴建华; 姚莉; 马飞; 吴伟伟

    2014-01-01

    With the constructions of high dam projects in China, the energy dissipation downstream of a dam becomes a serious concern. In this study, a multiple slit-type energy dissipater, with different reduction size slits in the outlet, is developed on the basis of conventional slit-type energy dissipaters, aiming to enhance the energy dissipation through the turbulence and the friction between the different layers of the jet flow and the air entrainment due to the increased surface of the flow to the air. The hydraulic characteristics of the energy dissipater are experimentally investigated by means of three sets of physical models in nine cases, to characterize the geometric parameters with suitable performance. The main concerns are the flow regime, the jet flow trajectory, the energy dissipation, the cavitation characteristics, and the flow choking. The results indicate that the dissipater enjoys a high energy dissipation ratio with suitable hydraulic performance comparing with the conventional slit-type energy dissipaters.

  5. Notch Activation Induces Endothelial Cell Senescence and Pro-inflammatory Response: Implication of Notch Signaling in Atherosclerosis

    Science.gov (United States)

    Liu, Zhao-Jun; Tan, Yurong; Beecham, Gary W.; Seo, David M.; Tian, Runxia; Li, Yan; Vazquez-Padron, Roberto I.; Pericak-Vance, Margaret; Vance, Jeffery M.; Goldschmidt-Clermont, Pascal J.; Livingstone, Alan S.; Velazquez, Omaida C.

    2012-01-01

    Objective Notch signaling plays pivotal roles in the pathogenesis of vascular disease. However, little is known about its role in atherosclerosis. We sought to investigate the potential involvement of the Notch signaling in atherosclerosis. Methods Expression of Notch pathway components in mouse and human aorta with or without atherosclerosis plaque was examined by immuno-histochemistry. Expression of Notch target genes in young versus aged human endothelial cells (EC) was examined by PCRArray and immunoblot. In vitro loss- and gain-of-function approaches were utilized to evaluate the role of Notch signaling in inducing EC senescence and secretion of pro-inflammatory cytokines by ProteinArray. Notch gene profile was studied in 1054 blood samples of patients with coronary artery disease (CAD). Genotyping was performed using the Genome-Wide Single Nucleotide Polymorphism (SNP) Array. Results Notch pathway components were upregulated in luminal EC at atherosclerotic lesions from mouse and human aortas. In addition, the Notch pathway was activated in aged but not young human EC. Enforced Notch activation resulted in EC senescence and significantly upregulated expression of several molecules implicated in the inflammatory response (IL-6/IL-8/IL-1α/RANTES/ICAM-1). The upregulated IL-6 was partially responsible for mediating leukocyte transendothelial migration. Genetic association analysis detected, of 82 SNPs across 6 Notch pathway genes analyzed, 4 SNPs with nominal association with CAD burden. Conclusion Notch pathway is activated in luminal EC at atherosclerotic plaques and results in pro-inflammatory response and senescence of EC. Notch signaling may be linked to human CAD risk. These findings implicate a potential involvement of Notch signaling in atherosclerosis. PMID:23078884

  6. Cavitation in Hydraulic Machinery

    Energy Technology Data Exchange (ETDEWEB)

    Kjeldsen, M.

    1996-11-01

    The main purpose of this doctoral thesis on cavitation in hydraulic machinery is to change focus towards the coupling of non-stationary flow phenomena and cavitation. It is argued that, in addition to turbulence, superimposed sound pressure fluctuations can have a major impact on cavitation and lead to particularly severe erosion. For the design of hydraulic devices this finding may indicate how to further limit the cavitation problems. Chapter 1 reviews cavitation in general in the context of hydraulic machinery, emphasizing the initial cavitation event and the role of the water quality. Chapter 2 discusses the existence of pressure fluctuations for situations common in such machinery. Chapter 3 on cavitation dynamics presents an algorithm for calculating the nucleation of a cavity cluster. Chapter 4 describes the equipment used in this work. 53 refs., 55 figs.,10 tabs.

  7. Sequential Notch activation regulates ventricular chamber development

    OpenAIRE

    D'Amato, Gaetano

    2016-01-01

    Tesis doctoral inédita, leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Bioquímica. Fecha de lectura: 15 de enero de 2016 Ventricular chamber morphogenesis is a beautiful example of tissue interactions orchestrating a precise gene regulatory network essential for tissue patterning, cellular proliferation and differentiation that ultimately lead to a fully compacted and functional adult ventricle. The Notch signaling pathway is a crucial regulator ...

  8. Notch signaling and development of the hematopoietic system.

    Science.gov (United States)

    Sandy, Ashley R; Jones, Morgan; Maillard, Ivan

    2012-01-01

    Notch signaling exerts multiple important functions in the hematopoietic system. Notch1-mediated signals are essential to induce the onset of definitive hematopoiesis within specialized domains of hemogenic endothelium in the fetal dorsal aorta. In contrast, Notch is dispensable for the subsequent maintenance of hematopoietic stem cells in the adult bone marrow. Notch is a key regulator of early T-cell development in the thymus. An expanding number of hematopoietic and lymphoid cell types have been reported to receive context-dependent inputs from the Notch pathway that regulate their differentiation and function. Progress in the field will continue to bring fundamental information about hematopoiesis and practical insights into the potential to modulate Notch signaling for therapeutic purposes.

  9. Notch flexure hinges: An effective theory

    Science.gov (United States)

    Tseytlin, Yakov M.

    2002-09-01

    This article presents effective tractable equations for rotational compliance (stiffness) of a simple monolithic flexure hinge with circular (radius R and crosspiece thickness t), elliptical [at semiaxis ax, ay, elliptical ratio epsilon (=ax/ay)] and other cross sections. These equations and the method by inverse conformal mapping of circular approximating contour used to derive them are different from the known and widely used theoretical equations originally derived in 1965 by Paros and Weisbord for circular notch hinges. Later it was found that the circular hinge represents the worst case error between known theoretical and finite element models. The conformal mapping equations data presented in this article are likely to be much closer (within less than 10%) to the finite element analysis and experimental data than other theoretical equations. In particular this is the case for circular notch hinges at relative thickness beta(=t/2R) in the range 0.01 to 0.3 and for elliptical hinges at the elliptical ratio epsilon=1 to 10. The derived general equation is common for all types of notch hinges whose profiles can be approximated by two shifted contiguous circles and includes material parameters with Young's modulus and Poisson's ratio. The latter is totally omitted in known theoretical solutions by other authors. New tractable equations are derived from the general equation on the basis of trigonometric functions' simplified series expansion in certain ranges of hinge crosspiece relative thickness. The corresponding graphs are presented. Experimental data were received by holographic interference and autocollimator measurement.

  10. Notch signaling in cancer stem cells.

    Science.gov (United States)

    Wang, Jialiang; Sullenger, Bruce A; Rich, Jeremy N

    2012-01-01

    Subpopulations of cancer cells with stem cell-like characteristics, termed cancer stem cells, have been identified in a wide range of human cancers. Cancer stem cells are defined by their ability to self-renew as well as recapitulate the original heterogeneity of cancer cells in culture and in serial xenotransplants. Not only are cancer stem cells highly tumorigenic, but these cells are implicated in tumor resistance to conventional chemotherapy and radiotherapy, thus highlighting their significance as therapeutic targets. Considerable similarities have been found between cancer stem cells and normal stem cells on their dependence on certain signaling pathways. More specifically, the core stem cell signaling pathways, such as the Wnt, Notch and Hedgehog pathways, also critically regulate the self-renewal and survival of cancer stem cells. While the oncogenic functions of Notch pathway have been well documented, its role in cancer stem cells is just emerging. In this chapter, we will discuss recent advances in cancer stem cell research and highlight the therapeutic potential of targeting Notch in cancer stem cells.

  11. Hydraulics and pneumatics

    CERN Document Server

    Parr, Andrew

    2006-01-01

    Nearly all industrial processes require objects to be moved, manipulated or subjected to some sort of force. This is frequently accomplished by means of electrical equipment (such as motors or solenoids), or via devices driven by air (pneumatics) or liquids (hydraulics).This book has been written by a process control engineer as a guide to the operation of hydraulic and pneumatic systems for all engineers and technicians who wish to have an insight into the components and operation of such a system.This second edition has been fully updated to include all recent developments su

  12. Popeye Project: Hydraulic umbilical

    Energy Technology Data Exchange (ETDEWEB)

    Jordan, K.G.; Williams, V.T.

    1996-12-31

    For the Popeye Project, the longest super-duplex hydraulic umbilical in the world was installed in the Gulf of Mexico. This paper reports on its selection and project implementation. Material selection addresses corrosion in seawater, water-based hydraulic fluid, and methanol. Five alternatives were considered: (1) carbon-steel with traditional coating and anodes, (2) carbon-steel coated with thermally sprayed aluminum, (3) carbon-steel sheathed in aluminum, (4) super-duplex, and (5) titanium. The merits and risks associated with each alternative are discussed. The manufacture and installation of the selected umbilical are also reported.

  13. Jet Car Track Site

    Data.gov (United States)

    Federal Laboratory Consortium — Located in Lakehurst, New Jersey, the Jet Car Track Site supports jet cars with J57 engines and has a maximum jet car thrust of 42,000 pounds with a maximum speed of...

  14. SIMULATION OF FLUID FLOW IN CHANNEL OF A NOVEL HYDRAULIC SHOCK GENERATOR

    Institute of Scientific and Technical Information of China (English)

    Fu Xin; Yang Huayong

    2000-01-01

    In order to improve the engineering performance of a novel hydraulic shock generator,the fluid flow inside its complex passages is numerically investigated.The effects of the inlet flow velocity upon the turbulence intensity of the jet flow are analyzed.The calculated pressure loss is experimentally verified with the consideration of temperature determined viscosity shifting.The results are used as the reference in the further development of the hydraulic shock generator

  15. Hydraulic Arm Modeling via Matlab SimHydraulics

    OpenAIRE

    Věchet, Stanislav; Krejsa, Jiří

    2009-01-01

    System modeling is a vital tool for cost reduction and design process speed up in most engineering fields. The paper is focused on modeling of hydraulic arm as a part of intelligent prosthesis project, in the form of 2DOF open kinematic chain. The arm model combines mechanical, hydraulic and electric subsystems and uses Matlab as modeling tool. SimMechanics Matlab extension is used for mechanical part modeling, SimHydraulics toolbox is used for modeling of hydraulic circuit used for actuating...

  16. Notch is required for long-term memory in Drosophila

    OpenAIRE

    Presente, Asaf; Boyles, Randy S.; Serway, Christine N.; de Belle, J. Steven; Andres, Andrew J.

    2004-01-01

    A role for Notch in the elaboration of existing neural processes is emerging that is distinct from the increasingly well understood function of this gene in binary cell-fate decisions. Several research groups, by using a variety of organisms, have shown that Notch is important in the development of neural ultrastructure. Simultaneously, Presenilin (Psn) was identified both as a key mediator of Notch signaling and as a site of genetic lesions that cause early-onset Alzheimer's disease. Here we...

  17. Finite element analysis of notch tensile behavior of alloy 718

    Science.gov (United States)

    Sridhar, A.; Srivathsa, B.

    2013-06-01

    Notch tensile behavior of alloy 718 is characterized in conventionally heat treated condition as a function of U and V notches at 25, 200 & 400 °C. The experimental results were then compared with the values obtained from simulation of notched geometries in ANSYS software using smooth specimen data. An excellent agreement is noticed between simulated and experimental true stress-true strain curves.

  18. Notch is required for long-term memory in Drosophila

    OpenAIRE

    Presente, Asaf; Boyles, Randy S.; Serway, Christine N.; de Belle, J. Steven; Andres, Andrew J.

    2004-01-01

    A role for Notch in the elaboration of existing neural processes is emerging that is distinct from the increasingly well understood function of this gene in binary cell-fate decisions. Several research groups, by using a variety of organisms, have shown that Notch is important in the development of neural ultrastructure. Simultaneously, Presenilin (Psn) was identified both as a key mediator of Notch signaling and as a site of genetic lesions that cause early-onset Alzheimer's disease. Here we...

  19. NOTCH INHIBITION AS A PROMISING NEW APPROACH TO CANCER THERAPY

    OpenAIRE

    Purow, Benjamin

    2012-01-01

    The Notch pathway powerfully influences stem cell maintenance, development and cell fate and is increasingly recognized for the key roles it plays in cancer. Notch promotes cell survival, angiogenesis and treatment resistance in numerous cancers, making it a promising target for cancer therapy. It also crosstalks with other critical oncogenes, providing a means to affect numerous signaling pathways with one intervention. While the gamma-secretaase inhibitors are the only form of Notch inhibit...

  20. Algorithm for Design of Digital Notch Filter Using Simulation

    Directory of Open Access Journals (Sweden)

    Amit Verma

    2013-08-01

    Full Text Available A smooth waveform is generated of low frequency signal can be achieved through the Digital Notch Filter. Noise can be easily eliminated from a speech signal by using a Notch filter. In this paper the design of notch filter using MATLAB has been designed and implemented. The performance and characteristics of the filter has been shown in the waveform in the conclusion part of the paper.

  1. Fbxw7 controls angiogenesis by regulating endothelial Notch activity.

    Directory of Open Access Journals (Sweden)

    Nanae Izumi

    Full Text Available Notch signaling controls fundamental aspects of angiogenic blood vessel growth including the selection of sprouting tip cells, endothelial proliferation and arterial differentiation. The E3 ubiquitin ligase Fbxw7 is part of the SCF protein complex responsible for the polyubiquitination and thereby proteasomal degradation of substrates such as Notch, c-Myc and c-Jun. Here, we show that Fbxw7 is a critical regulator of angiogenesis in the mouse retina and the zebrafish embryonic trunk, which we attribute to its role in the degradation of active Notch. Growth of retinal blood vessel was impaired and the Notch ligand Dll4, which is also a Notch target, upregulated in inducible and endothelial cell-specific Fbxw7(iECKO mutant mice. The stability of the cleaved and active Notch intracellular domain was increased after siRNA knockdown of the E3 ligase in cultured human endothelial cells. Injection of fbxw7 morpholinos interfered with the sprouting of zebrafish intersegmental vessels (ISVs. Arguing strongly that Notch and not other Fbxw7 substrates are primarily responsible for these phenotypes, the genetic inactivation of Notch pathway components reversed the impaired ISV growth in the zebrafish embryo as well as sprouting and proliferation in the mouse retina. Our findings establish that Fbxw7 is a potent positive regulator of angiogenesis that limits the activity of Notch in the endothelium of the growing vasculature.

  2. Upregulation of Notch pathway molecules in oral squamous cell carcinoma.

    Science.gov (United States)

    Hijioka, Hiroshi; Setoguchi, Takao; Miyawaki, Akihiko; Gao, Hui; Ishida, Takayuki; Komiya, Setsuro; Nakamura, Norifumi

    2010-04-01

    The constitutive activation of the Notch pathway has been demonstrated in various types of malignancies. However, it remains unclear how the Notch pathway is involved in the pathogenesis of oral squamous cell carcinoma (OSCC). We investigated the expression of Notch pathway molecules in OSCC cell lines and biopsy specimens and examined the effect of Notch pathway inhibition. Reverse transcription-polymerase chain reaction revealed upregulation of Notch1, Notch2, Jagged1, HES1 and HEY1 in both OSCC cell lines and biopsy specimens. Immunohistochemical examination showed that the Notch intracellular domain accumulates in the nucleus of cells in OSCC cell lines and biopsy specimens. In addition, Jagged1 is expressed in the cytoplasm of cells in OSCC cell lines and biopsy specimens. Furthermore, Notch pathway inhibition using a gamma-secretase inhibitor prevented the growth of OSCC in vitro. These findings suggest that inhibition of the Notch pathway suppresses OSCC growth and may be a useful approach for the treatment of patients with OSCC.

  3. Multiaxial fatigue strength of severely notched titanium grade 5 alloy

    Directory of Open Access Journals (Sweden)

    F. Berto

    2015-07-01

    Full Text Available The multiaxial fatigue strength of severely notched titanium grade 5 alloy (Ti-6Al-4V is investigated. Experimental tests under combined tension and torsion loading, both in-phase and out-of-phase, have been carried out on axisymmetric V-notched specimens considering different nominal load ratios (R = -1, 0. All specimens are characterized by a notch tip radius less than 0.1 mm, a notch depth of 6 mm and a notch opening angle equal to 90 degrees. The experimental data from multiaxial tests are compared with those from pure tension and pure torsion tests on un-notched and notched specimens, carried out at load ratio ranging from R = -3 to R = 0.5. In total, more than 160 new fatigue data are examined, first in terms of nominal stress amplitudes referred to the net area and then in terms of the local strain energy density averaged over a control volume surrounding the V-notch tip. The dependence of the control radius on the loading mode is analysed showing a very different notch sensitivity for tension and torsion. For the titanium alloy Ti-6Al-4V, the control volume is found to be strongly dependent on the loading mode

  4. The functional role of Notch signaling in human gliomas

    DEFF Research Database (Denmark)

    Stockhausen, Marie-Thérése; Kristoffersen, Karina; Poulsen, Hans Skovgaard

    2010-01-01

    have been referred to as brain cancer stem cells (bCSC), as they share similarities to normal neural stem cells in the brain. The Notch signaling pathway is involved in cell fate decisions throughout normal development and in stem cell proliferation and maintenance. The role of Notch in cancer is now...... firmly established, and recent data implicate a role for Notch signaling also in gliomas and bCSC. In this review, we explore the role of the Notch signaling pathway in gliomas with emphasis on its role in normal brain development and its interplay with pathways and processes that are characteristic...

  5. Notch signaling: its roles and therapeutic potential in hematological malignancies.

    Science.gov (United States)

    Gu, Yisu; Masiero, Massimo; Banham, Alison H

    2016-05-17

    Notch is a highly conserved signaling system that allows neighboring cells to communicate, thereby controlling their differentiation, proliferation and apoptosis, with the outcome of its activation being highly dependent on signal strength and cell type. As such, there is growing evidence that disturbances in physiological Notch signaling contribute to cancer development and growth through various mechanisms. Notch was first reported to contribute to tumorigenesis in the early 90s, through identification of the involvement of the Notch1 gene in the chromosomal translocation t(7;9)(q34;q34.3), found in a small subset of T-cell acute lymphoblastic leukemia. Since then, Notch mutations and aberrant Notch signaling have been reported in numerous other precursor and mature hematological malignancies, of both myeloid and lymphoid origin, as well as many epithelial tumor types. Of note, Notch has been reported to have both oncogenic and tumor suppressor roles, dependent on the cancer cell type. In this review, we will first give a general description of the Notch signaling pathway, and its physiologic role in hematopoiesis. Next, we will review the role of aberrant Notch signaling in several hematological malignancies. Finally, we will discuss current and potential future therapeutic approaches targeting this pathway.

  6. Involvement of Notch signaling in early chick ovarian follicle development.

    Science.gov (United States)

    Li, Jun; Zhao, Dan; Guo, Changquan; Li, Jian; Mi, Yuling; Zhang, Caiqiao

    2016-01-01

    The formation of primordial follicles is a crucial process in the establishment of follicle pools required for the female's reproductive life span. For laying hens, ample follicles are a prerequisite for high laying performance. Notch signaling plays critical roles in germ cell cysts breakdown and in the formation of primordial follicles. Here, we investigated the role of Notch signaling in the ovarian development of post-hatch chicks. Results showed that around post-hatch day 4 (H4), the germ cell cysts broke apart, oocytes became surrounded by squamous pregranulosa cells, and the primordial follicles were then formed. Subsequently, we detected the expression of Notch signaling-related genes including Notch receptors (Notch1, 2), ligands (Jag1, 2 and Dll1, 4), and target genes (Hes1, Hey1). These genes all showed expression at H4 and some of these genes were up-regulated during primordial follicle formation. To evaluate the Notch signaling requirement for early follicular development, we adopted an in vitro ovary culture system. Suppression of Notch signaling by γ-secretase inhibitor induced a decrease of primordial follicles and an increase of germ cells in cysts. Attenuating Notch signaling also inhibited the phosphatidylinositol 3-kinase/protein kinase B pathways and suppressed cadherin expression. These results suggest that Notch signaling is endowed with an indispensable role in primordial follicle formation in post-hatch chicks.

  7. HYDRAULICS, TUSCARAWAS COUNTY, OHIO, USA

    Data.gov (United States)

    Federal Emergency Management Agency, Department of Homeland Security — Hydraulic data include spatial datasets and data tables necessary for documenting the hydraulic procedures for estimating flood discharges for a flood insurance...

  8. Hydraulic hoist-press

    Energy Technology Data Exchange (ETDEWEB)

    Babayev, Z.B.; Abashev, Z.V.

    1982-01-01

    The efficiency expert of the Angrenskiy production-technological administration of the production association Sredazugol A. V. Bubnov has suggested a hydraulic hoist-press for repairing road equipment which is a device consisting of lifting mechanism, press and test stand for verifying the high pressure hoses and pumps.

  9. Modelling of Hydraulic Robot

    DEFF Research Database (Denmark)

    Madsen, Henrik; Zhou, Jianjun; Hansen, Lars Henrik

    1997-01-01

    This paper describes a case study of identifying the physical model (or the grey box model) of a hydraulic test robot. The obtained model is intended to provide a basis for model-based control of the robot. The physical model is formulated in continuous time and is derived by application...

  10. Water Treatment Technology - Hydraulics.

    Science.gov (United States)

    Ross-Harrington, Melinda; Kincaid, G. David

    One of twelve water treatment technology units, this student manual on hydraulics provides instructional materials for three competencies. (The twelve units are designed for a continuing education training course for public water supply operators.) The competencies focus on the following areas: head loss in pipes in series, function loss in…

  11. Water Hydraulic Systems

    DEFF Research Database (Denmark)

    Conrad, Finn

    2005-01-01

    The paper presents research results using IT-Tools for CAD and dynamic modelling, simulation, analysis, and design of water hydraulic actuators for motion control of machines, lifts, cranes and robots. Matlab/Simulink and CATIA are used as IT-Tools. The contributions include results from on-going...

  12. Numerical Analysis of Pelton Nozzle Jet Flow Behavior Considering Elbow Pipe

    Science.gov (United States)

    Chongji, Zeng; Yexiang, Xiao; Wei, Xu; Tao, Wu; Jin, Zhang; Zhengwei, Wang; Yongyao, Luo

    2016-11-01

    In Pelton turbine, the dispersion of cylindrical jet have a great influence on the energy interaction of jet and buckets. This paper simulated the internal flow of nozzle and the downstream free jet flow at 3 different needle strokes. The nozzle model consists of the elbow pipe and the needle rod which supported by 4 ribs. Homogenous model and SST k-ω model were adopted to simulate the unsteady two-phase jet flow. The development of free flow, including a contraction process followed by an expansion process, was analysed detailed as well as the influence of the nozzle geometry on the jet flow pattern. The increase of nozzle opening results in a more dispersion jet, which means a higher hydraulic loss. Upstream bend and ribs induce the secondary flow in the jet and decrease the jet concentration.

  13. Biochemical Characterization and Cellular Effects of CADASIL Mutants of NOTCH3

    OpenAIRE

    He Meng; Xiaojie Zhang; Genggeng Yu; Soo Jung Lee; Y Eugene Chen; Igor Prudovsky; Wang, Michael M.

    2012-01-01

    Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is the best understood cause of dominantly inherited stroke and results from NOTCH3 mutations that lead to NOTCH3 protein accumulation and selective arterial smooth muscle degeneration. Previous studies show that NOTCH3 protein forms multimers. Here, we investigate protein interactions between NOTCH3 and other vascular Notch isoforms and characterize the effects of elevated NOTCH3 on smooth mu...

  14. Effects of S1 Cleavage on the Structure, Surface Export, and Signaling Activity of Human Notch1 and Notch2

    Science.gov (United States)

    Gordon, Wendy R.; Vardar-Ulu, Didem; L'Heureux, Sarah; Ashworth, Todd; Malecki, Michael J.; Sanchez-Irizarry, Cheryll; McArthur, Debbie G.; Histen, Gavin; Mitchell, Jennifer L.; Aster, Jon C.; Blacklow, Stephen C.

    2009-01-01

    Background Notch receptors are normally cleaved during maturation by a furin-like protease at an extracellular site termed S1, creating a heterodimer of non-covalently associated subunits. The S1 site lies within a key negative regulatory region (NRR) of the receptor, which contains three highly conserved Lin12/Notch repeats and a heterodimerization domain (HD) that interact to prevent premature signaling in the absence of ligands. Because the role of S1 cleavage in Notch signaling remains unresolved, we investigated the effect of S1 cleavage on the structure, surface trafficking and ligand-mediated activation of human Notch1 and Notch2, as well as on ligand-independent activation of Notch1 by mutations found in human leukemia. Principal Findings The X-ray structure of the Notch1 NRR after furin cleavage shows little change when compared with that of an engineered Notch1 NRR lacking the S1-cleavage loop. Likewise, NMR studies of the Notch2 HD domain show that the loop containing the S1 site can be removed or cleaved without causing a substantial change in its structure. However, Notch1 and Notch2 receptors engineered to resist S1 cleavage exhibit unexpected differences in surface delivery and signaling competence: S1-resistant Notch1 receptors exhibit decreased, but detectable, surface expression and ligand-mediated receptor activation, whereas S1-resistant Notch2 receptors are fully competent for cell surface delivery and for activation by ligands. Variable dependence on S1 cleavage also extends to T-ALL-associated NRR mutations, as common class 1 mutations display variable decrements in ligand-independent activation when introduced into furin-resistant receptors, whereas a class 2 mutation exhibits increased signaling activity. Conclusions/Significance S1 cleavage has distinct effects on the surface expression of Notch1 and Notch2, but is not generally required for physiologic or pathophysiologic activation of Notch proteins. These findings are consistent with

  15. Effects of S1 cleavage on the structure, surface export, and signaling activity of human Notch1 and Notch2.

    Directory of Open Access Journals (Sweden)

    Wendy R Gordon

    Full Text Available Notch receptors are normally cleaved during maturation by a furin-like protease at an extracellular site termed S1, creating a heterodimer of non-covalently associated subunits. The S1 site lies within a key negative regulatory region (NRR of the receptor, which contains three highly conserved Lin12/Notch repeats and a heterodimerization domain (HD that interact to prevent premature signaling in the absence of ligands. Because the role of S1 cleavage in Notch signaling remains unresolved, we investigated the effect of S1 cleavage on the structure, surface trafficking and ligand-mediated activation of human Notch1 and Notch2, as well as on ligand-independent activation of Notch1 by mutations found in human leukemia.The X-ray structure of the Notch1 NRR after furin cleavage shows little change when compared with that of an engineered Notch1 NRR lacking the S1-cleavage loop. Likewise, NMR studies of the Notch2 HD domain show that the loop containing the S1 site can be removed or cleaved without causing a substantial change in its structure. However, Notch1 and Notch2 receptors engineered to resist S1 cleavage exhibit unexpected differences in surface delivery and signaling competence: S1-resistant Notch1 receptors exhibit decreased, but detectable, surface expression and ligand-mediated receptor activation, whereas S1-resistant Notch2 receptors are fully competent for cell surface delivery and for activation by ligands. Variable dependence on S1 cleavage also extends to T-ALL-associated NRR mutations, as common class 1 mutations display variable decrements in ligand-independent activation when introduced into furin-resistant receptors, whereas a class 2 mutation exhibits increased signaling activity.S1 cleavage has distinct effects on the surface expression of Notch1 and Notch2, but is not generally required for physiologic or pathophysiologic activation of Notch proteins. These findings are consistent with models for receptor activation in which

  16. Effects of S1 Cleavage on the Structure, Surface Export, and Signaling Activity of Human Notch1 and Notch2

    Energy Technology Data Exchange (ETDEWEB)

    Gordon, Wendy R.; Vardar-Ulu, Didem; L' Heureux, Sarah; Ashworth, Todd; Malecki, Michael J.; Sanchez-Irizarry, Cheryll; McArthur, Debbie G.; Histen, Gavin; Mitchell, Jennifer L.; Aster, Jon C.; Blacklow, Stephen C.; (BWH); (Wellesley)

    2009-09-25

    Notch receptors are normally cleaved during maturation by a furin-like protease at an extracellular site termed S1, creating a heterodimer of non-covalently associated subunits. The S1 site lies within a key negative regulatory region (NRR) of the receptor, which contains three highly conserved Lin12/Notch repeats and a heterodimerization domain (HD) that interact to prevent premature signaling in the absence of ligands. Because the role of S1 cleavage in Notch signaling remains unresolved, we investigated the effect of S1 cleavage on the structure, surface trafficking and ligand-mediated activation of human Notch1 and Notch2, as well as on ligand-independent activation of Notch1 by mutations found in human leukemia. The X-ray structure of the Notch1 NRR after furin cleavage shows little change when compared with that of an engineered Notch1 NRR lacking the S1-cleavage loop. Likewise, NMR studies of the Notch2 HD domain show that the loop containing the S1 site can be removed or cleaved without causing a substantial change in its structure. However, Notch1 and Notch2 receptors engineered to resist S1 cleavage exhibit unexpected differences in surface delivery and signaling competence: S1-resistant Notch1 receptors exhibit decreased, but detectable, surface expression and ligand-mediated receptor activation, whereas S1-resistant Notch2 receptors are fully competent for cell surface delivery and for activation by ligands. Variable dependence on S1 cleavage also extends to T-ALL-associated NRR mutations, as common class 1 mutations display variable decrements in ligand-independent activation when introduced into furin-resistant receptors, whereas a class 2 mutation exhibits increased signaling activity. S1 cleavage has distinct effects on the surface expression of Notch1 and Notch2, but is not generally required for physiologic or pathophysiologic activation of Notch proteins. These findings are consistent with models for receptor activation in which ligand-binding or

  17. Inclusive Jets in PHP

    Science.gov (United States)

    Roloff, P.

    Differential inclusive-jet cross sections have been measured in photoproduction for boson virtualities Q^2 < 1 GeV^2 with the ZEUS detector at HERA using an integrated luminosity of 300 pb^-1. Jets were identified in the laboratory frame using the k_T, anti-k_T or SIScone jet algorithms. Cross sections are presented as functions of the jet pseudorapidity, eta(jet), and the jet transverse energy, E_T(jet). Next-to-leading-order QCD calculations give a good description of the measurements, except for jets with low E_T(jet) and high eta(jet). The cross sections have the potential to improve the determination of the PDFs in future QCD fits. Values of alpha_s(M_Z) have been extracted from the measurements based on different jet algorithms. In addition, the energy-scale dependence of the strong coupling was determined.

  18. Aberrant Expression of Notch1 in Cervical Cancer

    Institute of Scientific and Technical Information of China (English)

    Li Sun; Qimin Zhan; Wenhua Zhang; Yongmei Song; Tong Tong

    2007-01-01

    OBJECTIVE To investigate the putative role of the Notch1 receptor in cervical cancer carcinogenesis and progression.METHODS The expression of the Notch1 protein was analyzed by a Western-blotting approach in 40 cervical cancer and 30 normal cervical tissues.Some tissues were examined using RT-PCR To determine Mrna levels.Celluar localization of the Notch1 protein in the paraffin-embedded cervical tissues was also analyzed by immunohistochemistry.RESULTS The Notch1 protein was detected in all 30 normal cervical tissues.In contrast.only 6 samples of 40 cervical cancer tissues showed Notch1 expression.The level of the Notch1 protein expression was significantly lower in cervical cancer tissues than that in normal tissue samples.In agreement with these observations.levels of Notch1 Mrna were found to be substantially down-regulated in cervical cancer tissues.In the immunohistochemistry staining assay,the Notch1 protein was shown to localize predominantly in the cytoplasm and nucleoli of the normal cervical squamous epithelium of the cervix,but no staining was observed in the cervical cancer cells.Notch1 expression was observed to correlate with the clinical disease stage.but there were no correlations with age,tumor size,grade or lymph node metastasis (P>0.05).The levels of Notchl protein expression were significantly higher in early stages(I~lla,66.7%) compared to those in the advanced stages (Iib~IV,12.6%)(P=0.001).CONCLUSION Notch1 may play a role as a tumor suppressor in cervical tumorigenesis.Determination of Notch1 expression may be helpful for preoperative diagnosis and accuracy of staging.But its clinical use for cervical cancer requires further investigation.

  19. Progress Report on Alloy 617 Notched Specimen Testing

    Energy Technology Data Exchange (ETDEWEB)

    McMurtrey, Michael David [Idaho National Lab. (INL), Idaho Falls, ID (United States); Wright, Richard Neil [Idaho National Lab. (INL), Idaho Falls, ID (United States); Lillo, Thomas Martin [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2016-08-01

    Creep behavior of Alloy 617 has been extensively characterized to support the development of a draft Code Case to qualify Alloy 617 in Section III division 5 of the ASME Boiler and Pressure Vessel Code. This will allow use of Alloy 617 in construction of nuclear reactor components at elevated temperatures and longer periods of time (up to 950°C and 100,000 hours). Prior to actual use, additional concerns not considered in the ASME code need to be addressed. Code Cases are based largely on uniaxial testing of smooth gage specimens. In service conditions, components will generally be under multi axial loading. There is also the concern of the behavior at discontinuities, such as threaded components. To address the concerns of multi axial creep behavior and at geometric discontinuities, notched specimens have been designed to create conditions representative of the states that service components experience. Two general notch geometries have been used for these series of tests: U notch and V notch specimens. The notches produce a tri axial stress state, though not uniform across the specimen. Characterization of the creep behavior of the U notch specimens and the creep rupture behavior of the V notch specimens provides a good approximation of the behavior expected of actual components. Preliminary testing and analysis have been completed and are reported in this document. This includes results from V notch specimens tested at 900°C and 800°C. Failure occurred in the smooth gage section of the specimen rather than at the root of the notch, though some damage was present at the root of the notch, where initial stress was highest. This indicates notch strengthening behavior in this material at these temperatures.

  20. AERATION EFFECT OF SUBMERGED JET ON HYDRAULIC CHARACTERISTICS

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    A water-air two-phase turbulence mathematical model was proposed, The mass-weighted average was adoptedfor velocity, air mass fraction and turbulent parameters. Thealgebraic stress equation was used to calculate the Reynoldsstress. The pulsating flux of air mass fraction was simulatedby employing the concept of the eddy viscosity. The numericalsimulation of aerated flow in plunge pool shows that, for the same depth, aeration may decrease the time-averaged pressureon pool floor and increase slightly the turbulent intensity. Thecomputed concentration and pressure distributions coincidewith the experimental data.

  1. Editorial on Future Jet Technologies

    Science.gov (United States)

    Gal-Or, Benjamin

    2014-12-01

    The jet engine is the prime flight controller in post-stall flight domains where conventional flight control fails, or when the engine prevents catastrophes in training, combat, loss of all airframe hydraulics (the engine retains its own hydraulics), loss of one engine, pilot errors, icing on the wings, landing gear and runway issues in takeoff and landing and in bad-whether recoveries. The scientific term for this revolutionary technology is "jet-steering", and in engineering practice - "thrust vectoring", or "TV". Jet-Steering in advanced fighter aircraft designs is integrated with stealth technology. The resulting classified Thrust-Vectoring-Stealth ("TVS") technology has generated a second jet-revolution by which all Air-&-Sea-Propulsion Science and R&D are now being reassessed. Classified F-22, X-47B/C and RQ-180 TVS-vehicles stand at the front of this revolution. But recent transfers of such sensitive technologies to South Korea and Japan [1-5], have raised various fundamental issues that are evaluated by this editorial-review. One, and perhaps a key conclusion presented here, means that both South Korea and Japan may have missed one of their air-&-sea defenses: To develop and field low-cost unmanned fleets of jet-drones, some for use with expensive, TVS-fighter aircraft in highly congested areas. In turn, the U.S., EU, Russia and China, are currently developing such fleets at various TVS levels and sizes. China, for instance, operates at least 15,000 drones ("UAVs") by 2014 in the civilian sector alone. All Chinese drones have been developed by at least 230 developers/manufacturers [1-16]. Mobile telecommunication of safe links between flyers and combat drones ("UCAVs") at increasingly deep penetrations into remote, congested areas, can gradually be purchased-developed-deployed and then operated by extant cader of tens of thousands "National Champion Flyers" who have already mastered the operation of mini-drones in free-to-all sport clubs under national

  2. Hydraulic manipulator research at ORNL

    Energy Technology Data Exchange (ETDEWEB)

    Kress, R.L.; Jansen, J.F. [Oak Ridge National Lab., TN (United States); Love, L.J. [Oak Ridge Inst. for Science and Education, TN (United States)

    1997-03-01

    Recently, task requirements have dictated that manipulator payload capacity increase to accommodate greater payloads, greater manipulator length, and larger environmental interaction forces. General tasks such as waste storage tank cleanup and facility dismantlement and decommissioning require manipulator life capacities in the range of hundreds of pounds rather than tens of pounds. To meet the increased payload capacities demanded by present-day tasks, manipulator designers have turned once again to hydraulics as a means of actuation. In order to successfully design, build, and deploy a new hydraulic manipulator (or subsystem), sophisticated modeling, analysis, and control experiments are usually needed. Oak Ridge National Laboratory (ORNL) has a history of projects that incorporate hydraulics technology, including mobile robots, teleoperated manipulators, and full-scale construction equipment. In addition, to support the development and deployment of new hydraulic manipulators, ORNL has outfitted a significant experimental laboratory and has developed the software capability for research into hydraulic manipulators, hydraulic actuators, hydraulic systems, modeling of hydraulic systems, and hydraulic controls. The purpose of this article is to describe the past hydraulic manipulator developments and current hydraulic manipulator research capabilities at ORNL. Included are example experimental results from ORNL`s flexible/prismatic test stand.

  3. Top Notch Support for eBooks

    OpenAIRE

    Setala, Tami; Amon, Sara

    2012-01-01

    Come learn tips and tricks for delivering top notch technical support for eBooks. Library staff are the front line technical support for a growing number of patrons with diverse technical abilities wanting to access eBooks. We’ll share VPL’s unique team approach and innovative techniques for delivering technical support for your eBook collection. In this session, participants will learn: How to apply reference interview skills to technical support. How to create effective tools to use w...

  4. Coronagraphic Notch Filter for Raman Spectroscopy

    Science.gov (United States)

    Cohen, David; Stirbl, Robert

    2004-01-01

    A modified coronagraph has been proposed as a prototype of improved notch filters in Raman spectrometers. Coronagraphic notch filters could offer alternatives to both (1) the large and expensive double or triple monochromators in older Raman spectrometers and (2) holographic notch filters, which are less expensive but are subject to environmental degradation as well as to limitations of geometry and spectral range. Measurement of a Raman spectrum is an exercise in measuring and resolving faint spectral lines close to a bright peak: In Raman spectroscopy, a monochromatic beam of light (the pump beam) excites a sample of material that one seeks to analyze. The pump beam generates a small flux of scattered light at wavelengths slightly greater than that of the pump beam. The shift in wavelength of the scattered light from the pump wavelength is known in the art as the Stokes shift. Typically, the flux of scattered light is of the order of 10 7 that of the pump beam and the Stokes shift lies in the wave-number range of 100 to 3,000 cm 1. A notch filter can be used to suppress the pump-beam spectral peak while passing the nearby faint Raman spectral lines. The basic principles of design and operation of a coronagraph offer an opportunity for engineering the spectral transmittance of the optics in a Raman spectrometer. A classical coronagraph may be understood as two imaging systems placed end to end, such that the first system forms an intermediate real image of a nominally infinitely distant object and the second system forms a final real image of the intermediate real image. If the light incident on the first telescope is collimated, then the intermediate image is a point-spread function (PSF). If an appropriately tailored occulting spot (e.g., a Gaussian-apodized spot with maximum absorption on axis) is placed on the intermediate image plane, then the instrument inhibits transmission of light from an on-axis source. However, the PSFs of off-axis light sources are

  5. TEMPORAL EXPRESSION OF NOTCH RECEPTORS DURING LUNG DEVELOPMENT IN RAT

    Institute of Scientific and Technical Information of China (English)

    ZHANG Qian-shen; CHANG Li-wen; LIU Han-chu; RONG Zhi-hu; CHEN Hong-bing

    2005-01-01

    Objective To investigate the temporal expression of Notch receptors in developing lungs of rats and to explore the regulating role of Notch in lung development. Methods We studied the expression of Notch1,2,3 isforms in embryonic days 18,20,21 and postnatal days 1,4,7,14, 21 rat lungs. Six rats of each group were used to assess lung histologic changes by HE staining and expression of Notch in lungs by immunohistochemistry. Total RNA was extracted by Trizol reagent from the frozen lung tissues. mRNA levels of Notch were measured by reverse transcription polymerase chain reaction (RT-PCR). Results It is showed that Notch1-3 mainly localized in the airway surface epithelium、alveolar epithelium during the psdueoglandular stage, and reached the peaks at canalicular period. The expression patterns of Notch1-3 were changed with the fetal age. Conclusion These results support multiple roles for Notch1,2,and 3 receptor activation during lung development, probably not only modulating the process of branching morphogenesis but also involved in determining the cell differentiation fate in fetal alveolar epithelium.

  6. Microstructure-Sensitive Fatigue Design of Notched Components

    Science.gov (United States)

    2015-01-26

    Materials , World journal of mechanics (05 2013) TOTAL: 2 Books Number of Manuscripts: Patents Submitted Patents Awarded Awards Graduate Students...Received Book TOTAL: Received Book Chapter TOTAL: PERCENT_SUPPORTEDNAME FTE Equivalent: Total Number: Discipline Oluwamayowa Okeyoyin 1.00 Li Shi 1.00...complexity of realistic microstructures. Notch size effects and notch root inelastic behavior are combined with probability distributions of

  7. Regulation of cellular metabolism by the Notch receptor signalling pathway

    OpenAIRE

    2012-01-01

    Seven genes involved in metabolism were tested as direct targets of the Notch signalling pathway. For each gene the occupancy of its enhancers by Su(H), its transcriptional response to Notch pathway and its biological functionality was verified in vitro and in vivo.

  8. Notch intracellular domain overexpression in adipocytes confers lipodystrophy in mice

    Directory of Open Access Journals (Sweden)

    Dionysios V. Chartoumpekis

    2015-07-01

    Conclusions: Increased Notch signaling in adipocytes in mice results in blocked expansion of white adipose tissue which leads to ectopic accumulation of lipids and insulin resistance, thus to a lipodystrophic phenotype. These results suggest that further investigation of the role of Notch signaling in adipocytes could lead to the manipulation of this pathway for therapeutic interventions in metabolic disease.

  9. Notch sensitivity of ductile metallic foams : A computational study

    NARCIS (Netherlands)

    Mangipudi, K. R.; Onck, P. R.

    2011-01-01

    The role of notches in the fracture strength of metal foams has been studied using a multiscale model based on a two-dimensional Voronoi representation of the cellular architecture. The effect of the crack length to the specimen width ratio on the net section strength of double edge notch (DEN) spec

  10. Production laser hardfacing of jet engine turbine blades

    Science.gov (United States)

    Duhamel, R. F.; Banas, C. M.; Kosenski, R. L.

    1986-01-01

    A high wear point exists at the notch between adjacent blades forming the outer shroud of a jet engine turbine stage. This notch is commonly hardfaced to reduce wear and improve turbine blade endurance. Until recently, the blades were manually hardfaced by the gas tungsten arc process. A laser hardfacing process was developed for this application which has increased production rates and reduced rework requirements. The laser's precise energy control, inherent repeatability, and ability to be automated are the principal reasons for these process improvements. Laser hardfacing fundamentals and process development are described. Production equipment characteristics are reviewed and unique features of the process are identified. Finally, the results of several years of production hardfacing experiences are discussed.

  11. HYDRAULIC ELEVATOR INSTALLATION ESTIMATION FOR THE WATER SOURCE WELL SAND-PACK CLEANING UP

    Directory of Open Access Journals (Sweden)

    V. V. Ivashechkin

    2016-01-01

    Full Text Available The article offers design of a hydraulic elevator installation for cleaning up water-source wells of sand packs. It considerers the installation hydraulic circuit according to which the normal pump feeds the high-level tank water into the borehole through two parallel water lines. The water-jet line with washing nozzle for destroying the sand-pack and the supply pipe-line coupled with the operational nozzle of the hydraulic elevator containing the inlet and the supply pipelines for respectively intaking the hydromixture and removing it from the well. The paper adduces equations for fluid motion in the supply and the water-jet pipelines and offers expressions for evaluating the required heads in them. For determining water flow in the supply and the water-jet pipe lines the author proposes to employ graphical approach allowing finding the regime point in Q–H chart by means of building characteristics of the pump and the pipe-lines. For calculating the useful vertical head, supply and dimensions of the hydraulic elevator the article employs the equation of motion quantity with consistency admission of the motion quantity before and after mixing the flows in the hydraulic elevator. The suggested correlations for evaluating the hydraulic elevator efficiency determine the sand pack removal duration as function of its sizes and the ejected fluid flow rate. A hydraulic-elevator installation parameters estimation example illustrates removing a sand pack from a water-source borehole of 41 m deep and 150 mm diameter bored in the village of Uzla of Myadelsk region, of Minsk oblast. The working efficiency of a manufactured and laboratory tested engineering prototype of the hydraulic elevator installation was acknowledged in actual tests at the indicated borehole site. With application of graphical approach, the suggested for the hydraulic elevator installation parameters calculation procedure allows selecting, with given depth and the borehole diameter

  12. Remotely Adjustable Hydraulic Pump

    Science.gov (United States)

    Kouns, H. H.; Gardner, L. D.

    1987-01-01

    Outlet pressure adjusted to match varying loads. Electrohydraulic servo has positioned sleeve in leftmost position, adjusting outlet pressure to maximum value. Sleeve in equilibrium position, with control land covering control port. For lowest pressure setting, sleeve shifted toward right by increased pressure on sleeve shoulder from servovalve. Pump used in aircraft and robots, where hydraulic actuators repeatedly turned on and off, changing pump load frequently and over wide range.

  13. Notch is required for long-term memory in Drosophila.

    Science.gov (United States)

    Presente, Asaf; Boyles, Randy S; Serway, Christine N; de Belle, J Steven; Andres, Andrew J

    2004-02-10

    A role for Notch in the elaboration of existing neural processes is emerging that is distinct from the increasingly well understood function of this gene in binary cell-fate decisions. Several research groups, by using a variety of organisms, have shown that Notch is important in the development of neural ultrastructure. Simultaneously, Presenilin (Psn) was identified both as a key mediator of Notch signaling and as a site of genetic lesions that cause early-onset Alzheimer's disease. Here we demonstrate that Notch loss of function produces memory deficits in Drosophila melanogaster. The effects are specific to long-term memory, which is thought to depend on ultrastructural remodeling. We propose that Notch plays an important role in the neural plasticity underlying consolidated memory.

  14. Oncogenic role of the Notch pathway in primary liver cancer

    Science.gov (United States)

    LU, JIE; XIA, YUJING; CHEN, KAN; ZHENG, YUANYUAN; WANG, JIANRONG; LU, WENXIA; YIN, QIN; WANG, FAN; ZHOU, YINGQUN; GUO, CHUANYONG

    2016-01-01

    Primary liver cancer, which includes hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and fibrolamellar HCC, is one of the most common malignancies and the third leading cause of cancer-associated mortality, worldwide. Despite the development of novel therapies, the prognosis of liver cancer patients remains extremely poor. Thus, investigation of the genetic background and molecular mechanisms underlying the development and progression of this disease has gained significant attention. The Notch signaling pathway is a crucial determinant of cell fate during development and disease in several organs. In the liver, Notch signaling is involved in biliary tree development and tubulogenesis, and is also significant in the development of HCC and ICC. These findings suggest that the modulation of Notch pathway activity may have therapeutic relevance. The present review summarizes Notch signaling during HCC and ICC development and discusses the findings of recent studies regarding Notch expression, which reveal novel insights into its function in liver cancer progression. PMID:27347091

  15. Botch (NPG7) Promotes Neurogenesis by Antagonizing Notch

    Science.gov (United States)

    Chi, Zhikai; Zhang, Jianmin; Tokunaga, Akinori; Harraz, Maged M.; Byrne, Sean T.; Dolinko, Andrew; Xu, Jing; Blackshaw, Seth; Gaiano, Nicholas; Dawson, Ted M.; Dawson, Valina L.

    2012-01-01

    SUMMARY Regulation of self-renewal and differentiation of neural stem cells is still poorly understood. Here we investigate the role of a developmentally expressed protein, Botch, which blocks Notch, in neocortical development. Downregulation of Botch in vivo leads to cellular retention in the ventricular and subventricular zones, whereas overexpression of Botch drives neural stem cells into the intermediate zone and cortical plate. In vitro neurosphere and differentiation assays indicate that Botch regulates neurogenesis by promoting neuronal differentiation. Botch prevents cell surface presentation of Notch by inhibiting the S1 furin-like cleavage of Notch, maintaining Notch in the immature full-length form. Understanding the function of Botch expands our knowledge regarding both the regulation of Notch signaling and the complex signaling mediating neuronal development. PMID:22445366

  16. Optical notch filter design based on digital signal processing

    Institute of Scientific and Technical Information of China (English)

    GUO Sen; ZHANG Juan; LI Xue

    2011-01-01

    Based on digital signal processing theory, a novel method of designing optical notch filter is proposed for Mach-Zehnder interferometer with cascaded optical fiber rings coupled structure. The method is simple and effective, and it can be used to implement the designing of the optical notch filter which has arbitrary number of notch points in one free spectrum range (FSR). A design example of notch filter based on cascaded single-fiber-rings is given. On this basis, an improved cascaded double-fiber-rings structure is presented to eliminate the effect of phase shift caused by the single-fiber-ring structure. This new structure can improve the stability and applicability of system. The change of output intensity spectrum is finally investigated for each design parameter and the tuning characteristics of the notch filter are also discussed.

  17. Undular Hydraulic Jump

    Directory of Open Access Journals (Sweden)

    Oscar Castro-Orgaz

    2015-04-01

    Full Text Available The transition from subcritical to supercritical flow when the inflow Froude number Fo is close to unity appears in the form of steady state waves called undular hydraulic jump. The characterization of the undular hydraulic jump is complex due to the existence of a non-hydrostatic pressure distribution that invalidates the gradually-varied flow theory, and supercritical shock waves. The objective of this work is to present a mathematical model for the undular hydraulic jump obtained from an approximate integration of the Reynolds equations for turbulent flow assuming that the Reynolds number R is high. Simple analytical solutions are presented to reveal the physics of the theory, and a numerical model is used to integrate the complete equations. The limit of application of the theory is discussed using a wave breaking condition for the inception of a surface roller. The validity of the mathematical predictions is critically assessed using physical data, thereby revealing aspects on which more research is needed

  18. Gauging NOTCH1 Activation in Cancer Using Immunohistochemistry.

    Directory of Open Access Journals (Sweden)

    Michael J Kluk

    Full Text Available Fixed, paraffin-embedded (FPE tissues are a potentially rich resource for studying the role of NOTCH1 in cancer and other pathologies, but tests that reliably detect activated NOTCH1 (NICD1 in FPE samples have been lacking. Here, we bridge this gap by developing an immunohistochemical (IHC stain that detects a neoepitope created by the proteolytic cleavage event that activates NOTCH1. Following validation using xenografted cancers and normal tissues with known patterns of NOTCH1 activation, we applied this test to tumors linked to dysregulated Notch signaling by mutational studies. As expected, frequent NICD1 staining was observed in T lymphoblastic leukemia/lymphoma, a tumor in which activating NOTCH1 mutations are common. However, when IHC was used to gauge NOTCH1 activation in other human cancers, several unexpected findings emerged. Among B cell tumors, NICD1 staining was much more frequent in chronic lymphocytic leukemia than would be predicted based on the frequency of NOTCH1 mutations, while mantle cell lymphoma and diffuse large B cell lymphoma showed no evidence of NOTCH1 activation. NICD1 was also detected in 38% of peripheral T cell lymphomas. Of interest, NICD1 staining in chronic lymphocytic leukemia cells and in angioimmunoblastic lymphoma was consistently more pronounced in lymph nodes than in surrounding soft tissues, implicating factors in the nodal microenvironment in NOTCH1 activation in these diseases. Among carcinomas, diffuse strong NICD1 staining was observed in 3.8% of cases of triple negative breast cancer (3 of 78 tumors, but was absent from 151 non-small cell lung carcinomas and 147 ovarian carcinomas. Frequent staining of normal endothelium was also observed; in line with this observation, strong NICD1 staining was also seen in 77% of angiosarcomas. These findings complement insights from genomic sequencing studies and suggest that IHC staining is a valuable experimental tool that may be useful in selection of

  19. The Giant Jet

    Science.gov (United States)

    Neubert, T.; Chanrion, O.; Arnone, E.; Zanotti, F.; Cummer, S.; Li, J.; Füllekrug, M.; van der Velde, O.

    2012-04-01

    Thunderstorm clouds may discharge directly to the ionosphere in spectacular luminous jets - the longest electric discharges on our planet. The electric properties of jets, such as their polarity, conductivity, and currents, have been predicted by models, but are poorly characterized by measurements. Here we present an analysis of the first gigantic jet that with certainty has a positive polarity. The jet region in the mesosphere was illuminated by an unusual sprite discharge generated by a positive cloud-to-ground lightning flash shortly after the onset of the jet. The sprite appeared with elements in a ring at ~40 km distance around the jet, the elements pointing curving away from the jet. This suggests that the field close the jet partially cancels the field driving the sprite. From a simple model of the event we conclude that a substantial portion of the positive cloud potential must be carried to ~50 km altitude, which is also consistent with the observed channel expansion and the electromagnetic radiation associated with the jet. It is further shown that blue jets are likely to substantially modify the free electron content in the lower ionosphere because of increased electron attachment driven by the jet electric field. The model further makes clear the relationship between jets, gigantic jets, and sprites. This is the first time that sprites are used for sounding the properties of the mesosphere. The observations presented here will allow evaluation of theories for jet and gigantic jet generation and of their influence on the atmosphere-ionosphere system.

  20. Scalable Notch Antenna System for Multiport Applications

    Directory of Open Access Journals (Sweden)

    Abdurrahim Toktas

    2016-01-01

    Full Text Available A novel and compact scalable antenna system is designed for multiport applications. The basic design is built on a square patch with an electrical size of 0.82λ0×0.82λ0 (at 2.4 GHz on a dielectric substrate. The design consists of four symmetrical and orthogonal triangular notches with circular feeding slots at the corners of the common patch. The 4-port antenna can be simply rearranged to 8-port and 12-port systems. The operating band of the system can be tuned by scaling (S the size of the system while fixing the thickness of the substrate. The antenna system with S: 1/1 in size of 103.5×103.5 mm2 operates at the frequency band of 2.3–3.0 GHz. By scaling the antenna with S: 1/2.3, a system of 45×45 mm2 is achieved, and thus the operating band is tuned to 4.7–6.1 GHz with the same scattering characteristic. A parametric study is also conducted to investigate the effects of changing the notch dimensions. The performance of the antenna is verified in terms of the antenna characteristics as well as diversity and multiplexing parameters. The antenna system can be tuned by scaling so that it is applicable to the multiport WLAN, WIMAX, and LTE devices with port upgradability.

  1. Benchmark notch test for life prediction

    Science.gov (United States)

    Domas, P. A.; Yau, J.; Sharpe, W. N.; Ward, M.

    1982-01-01

    Aircraft gas turbine engine components are subjected to severe stress, temperature, and environmental conditions. Economic and reliabilty demands have prompted inordinate effort in development of analytic methods to predict stresses and strains in aircraft engines. There remains, however, the need to check or verify these analytical methodologies against actual experimental data measurements. The laser interferometric strain displacement gage was recognized as having the potential to accomplish this task and was employed in this program. The actual strains incurred at the root of a discontinuity in cyclically loaded test samples subjected to inelastic deformation at high temperature where creep deformation readily occur were measured. The steady-state, cyclic stress-strain response at the root of the discontinuity in the tested samples was analyzed for comparison with the measured results. A comprehensive set of local notch root strain measurements for a variety of load patterns in an Inconel 718 notch specimen at 649 C (1200 F) was obtained and documented using the laser interferometric strain displacement gage.

  2. MAGP2 controls Notch via interactions with RGD binding integrins: Identification of a Novel ECM – Integrin – Notch Signaling Axis

    Science.gov (United States)

    Deford, Peter; Brown, Kasey; Richards, Rae Lee; King, Aric; Newburn, Kristin; Westover, Katherine; Albig, Allan R.

    2016-01-01

    Canonical Notch signaling involves Notch receptor activation via interaction with cell surface bound Notch ligand. Recent findings also indicate that Notch signaling may be modulated by cross-talk with other signaling mechanisms. The ECM protein MAGP2 was previously shown to regulate Notch in a cell type dependent manner, although the molecular details of this interaction have not been dissected. Here, we report that MAGP2 cell type specific control of Notch is independent of individual Notch receptor-ligand combinations but dependent on interaction with RGD binding integrins. Overexpressed MAGP2 was found to suppress transcriptional activity from the Notch responsive Hes1 promoter activity in endothelial cells, while overexpression of a RGD→RGE MAGP2 mutant increased Notch signaling in the same cell type. This effect was not unique to MAGP2 since the RGD domain of the ECM protein EGFL7 was also found to be an important modulator of Hes1 promoter activity. Independently of MAGP2 or EGFL7, inhibition of RGD-binding integrins with soluble RGD peptides also increased accumulation of active N1ICD fragments and Notch responsive promoter activity independently of changes in Notch1, Jag1, or Dll4 expression. Finally, β1 or β3 integrin blocking antibodies also enhanced Notch signaling. Collectively, these results answer the question of how MAGP2 controls cell type dependent Notch signaling, but more importantly uncover a new mechanism to understand how extracellular matricies and cellular environments impact Notch signaling. PMID:26808411

  3. Effects of varying Notch1 signal strength on embryogenesis and vasculogenesis in compound mutant heterozygotes

    Directory of Open Access Journals (Sweden)

    Ge Changhui

    2010-03-01

    Full Text Available Abstract Background Identifying developmental processes regulated by Notch1 can be addressed in part by characterizing mice with graded levels of Notch1 signaling strength. Here we examine development in embryos expressing various combinations of Notch1 mutant alleles. Mice homozygous for the hypomorphic Notch112f allele, which removes the single O-fucose glycan in epidermal growth factor-like repeat 12 (EGF12 of the Notch1 ligand binding domain (lbd, exhibit reduced growth after weaning and defective T cell development. Mice homozygous for the inactive Notch1lbd allele express Notch1 missing an ~20 kDa internal segment including the canonical Notch1 ligand binding domain, and die at embryonic day ~E9.5. The embryonic and vascular phenotypes of compound heterozygous Notch112f/lbd embryos were compared with Notch1+/12f, Notch112f/12f, and Notch1lbd/lbd embryos. Embryonic stem (ES cells derived from these embryos were also examined in Notch signaling assays. While Notch1 signaling was stronger in Notch112f/lbd compound heterozygotes compared to Notch1lbd/lbd embryos and ES cells, Notch1 signaling was even stronger in embryos carrying Notch112f and a null Notch1 allele. Results Mouse embryos expressing the hypomorphic Notch112f allele, in combination with the inactive Notch1lbd allele which lacks the Notch1 ligand binding domain, died at ~E11.5-12.5. Notch112f/lbd ES cells signaled less well than Notch112f/12f ES cells but more strongly than Notch1lbd/lbd ES cells. However, vascular defects in Notch112f/lbd yolk sac were severe and similar to Notch1lbd/lbd yolk sac. By contrast, vascular disorganization was milder in Notch112f/lbd compared to Notch1lbd/lbd embryos. The expression of Notch1 target genes was low in Notch112f/lbd yolk sac and embryo head, whereas Vegf and Vegfr2 transcripts were increased. The severity of the compound heterozygous Notch112f/lbd yolk sac phenotype suggested that the allelic products may functionally interact. By

  4. Hydraulic System Design of Hydraulic Actuators for Large Butterfly Valves

    OpenAIRE

    HUANG, Ye; Liu, Changsheng; Shiongur Bamed

    2014-01-01

    Hydraulic control systems of butterfly valves are presently valve-controlled and pump-controlled. Valve-controlled hydraulic systems have serious power loss and generate much heat during throttling. Pump-controlled hydraulic systems have no overflow or throttling losses but are limited in the speed adjustment of the variable-displacement pump, generate much noise, pollute the environment, and have motor power that does not match load requirements, resulting in low efficiency under...

  5. Dual Roles of O-Glucose Glycans Redundant with Monosaccharide O-Fucose on Notch in Notch Trafficking.

    Science.gov (United States)

    Matsumoto, Kenjiroo; Ayukawa, Tomonori; Ishio, Akira; Sasamura, Takeshi; Yamakawa, Tomoko; Matsuno, Kenji

    2016-06-24

    Notch is a transmembrane receptor that mediates cell-cell interactions and controls various cell-fate specifications in metazoans. The extracellular domain of Notch contains multiple epidermal growth factor (EGF)-like repeats. At least five different glycans are found in distinct sites within these EGF-like repeats. The function of these individual glycans in Notch signaling has been investigated, primarily by disrupting their individual glycosyltransferases. However, we are just beginning to understand the potential functional interactions between these glycans. Monosaccharide O-fucose and O-glucose trisaccharide (O-glucose-xylose-xylose) are added to many of the Notch EGF-like repeats. In Drosophila, Shams adds a xylose specifically to the monosaccharide O-glucose. We found that loss of the terminal dixylose of O-glucose-linked saccharides had little effect on Notch signaling. However, our analyses of double mutants of shams and other genes required for glycan modifications revealed that both the monosaccharide O-glucose and the terminal dixylose of O-glucose-linked saccharides function redundantly with the monosaccharide O-fucose in Notch activation and trafficking. The terminal dixylose of O-glucose-linked saccharides and the monosaccharide O-glucose were required in distinct Notch trafficking processes: Notch transport from the apical plasma membrane to adherens junctions, and Notch export from the endoplasmic reticulum, respectively. Therefore, the monosaccharide O-glucose and terminal dixylose of O-glucose-linked saccharides have distinct activities in Notch trafficking, although a loss of these activities is compensated for by the presence of monosaccharide O-fucose. Given that various glycans attached to a protein motif may have redundant functions, our results suggest that these potential redundancies may lead to a serious underestimation of glycan functions.

  6. Hydraulic System Design of Hydraulic Actuators for Large Butterfly Valves

    Directory of Open Access Journals (Sweden)

    Ye HUANG

    2014-09-01

    Full Text Available Hydraulic control systems of butterfly valves are presently valve-controlled and pump-controlled. Valve-controlled hydraulic systems have serious power loss and generate much heat during throttling. Pump-controlled hydraulic systems have no overflow or throttling losses but are limited in the speed adjustment of the variable-displacement pump, generate much noise, pollute the environment, and have motor power that does not match load requirements, resulting in low efficiency under light loads and wearing of the variable-displacement pump. To overcome these shortcomings, this article designs a closed hydraulic control system in which an AC servo motor drives a quantitative pump that controls a spiral swinging hydraulic cylinder, and analyzes and calculates the structure and parameters of a spiral swinging hydraulic cylinder. The hydraulic system adjusts the servo motor’s speed according to the requirements of the control system, and the motor power matches the power provided to components, thus eliminating the throttling loss of hydraulic circuits. The system is compact, produces a large output force, provides stable transmission, has a quick response, and is suitable as a hydraulic control system of a large butterfly valve.

  7. NACK is an integral component of the Notch transcriptional activation complex and is critical for development and tumorigenesis.

    Science.gov (United States)

    Weaver, Kelly L; Alves-Guerra, Marie-Clotilde; Jin, Ke; Wang, Zhiqiang; Han, Xiaoqing; Ranganathan, Prathibha; Zhu, Xiaoxia; DaSilva, Thiago; Liu, Wei; Ratti, Francesca; Demarest, Renee M; Tzimas, Cristos; Rice, Meghan; Vasquez-Del Carpio, Rodrigo; Dahmane, Nadia; Robbins, David J; Capobianco, Anthony J

    2014-09-01

    The Notch signaling pathway governs many distinct cellular processes by regulating transcriptional programs. The transcriptional response initiated by Notch is highly cell context dependent, indicating that multiple factors influence Notch target gene selection and activity. However, the mechanism by which Notch drives target gene transcription is not well understood. Herein, we identify and characterize a novel Notch-interacting protein, Notch activation complex kinase (NACK), which acts as a Notch transcriptional coactivator. We show that NACK associates with the Notch transcriptional activation complex on DNA, mediates Notch transcriptional activity, and is required for Notch-mediated tumorigenesis. We demonstrate that Notch1 and NACK are coexpressed during mouse development and that homozygous loss of NACK is embryonic lethal. Finally, we show that NACK is also a Notch target gene, establishing a feed-forward loop. Thus, our data indicate that NACK is a key component of the Notch transcriptional complex and is an essential regulator of Notch-mediated tumorigenesis and development.

  8. Triaxial coreflood study of the hydraulic fracturing of Utica Shale

    Science.gov (United States)

    Carey, J. W.; Frash, L.; Viswanathan, H. S.

    2015-12-01

    One of the central questions in unconventional oil and gas production research is the cause of limited recovery of hydrocarbon. There are many hypotheses including: 1) inadequate penetration of fractures within the stimulated volume; 2) limited proppant delivery; 3) multiphase flow phenomena that blocks hydrocarbon migration; etc. Underlying any solution to this problem must be an understanding of the hydrologic properties of hydraulically fractured shale. In this study, we conduct triaxial coreflood experiments using a gasket sealing mechanism to characterize hydraulic fracture development and permeability of Utica Shale samples. Our approach also includes fracture propagation with proppants. The triaxial coreflood experiments were conducted with an integrated x-ray tomography system that allows direct observation of fracture development using x-ray video radiography and x-ray computed tomography at elevated pressure. A semi-circular, fracture initiation notch was cut into an end-face of the cylindrical samples (1"-diameter with lengths from 0.375 to 1"). The notch was aligned parallel with the x-ray beam to allow video radiography of fracture growth as a function of injection pressure. The proppants included tungsten powder that provided good x-ray contrast for tracing proppant delivery and distribution within the fracture system. Fractures were propagated at injection pressures in excess of the confining pressure and permeability measurements were made in samples where the fractures propagated through the length of the sample, ideally without penetrating the sample sides. Following fracture development, permeability was characterized as a function of hydrostatic pressure and injection pressure. X-ray video radioadiography was used to study changes in fracture aperture in relation to permeability and proppant embedment. X-ray tomography was collected at steady-state conditions to fully characterize fracture geometry and proppant distribution.

  9. Notch3 marks clonogenic mammary luminal progenitor cells in vivo.

    Science.gov (United States)

    Lafkas, Daniel; Rodilla, Veronica; Huyghe, Mathilde; Mourao, Larissa; Kiaris, Hippokratis; Fre, Silvia

    2013-10-14

    The identity of mammary stem and progenitor cells remains poorly understood, mainly as a result of the lack of robust markers. The Notch signaling pathway has been implicated in mammary gland development as well as in tumorigenesis in this tissue. Elevated expression of the Notch3 receptor has been correlated to the highly aggressive "triple negative" human breast cancer. However, the specific cells expressing this Notch paralogue in the mammary gland remain unknown. Using a conditionally inducible Notch3-CreERT2(SAT) transgenic mouse, we genetically marked Notch3-expressing cells throughout mammary gland development and followed their lineage in vivo. We demonstrate that Notch3 is expressed in a highly clonogenic and transiently quiescent luminal progenitor population that gives rise to a ductal lineage. These cells are capable of surviving multiple successive pregnancies, suggesting a capacity to self-renew. Our results also uncover a role for the Notch3 receptor in restricting the proliferation and consequent clonal expansion of these cells.

  10. Bed profile downstream compound sharp crested V-notch weir

    Directory of Open Access Journals (Sweden)

    Mohammad Mahmoud Ibrahim

    2015-09-01

    Full Text Available Triangular weirs are commonly used to measure discharge in open channel flow. They represent an inexpensive, reliable methodology to monitor water allocation. A compound sharp-crested weir consisting of two triangular parts with different notch angles was used. The lower triangular part of the weir handles the normal range of discharges while the upper part measures the higher peak flows. This paper evaluates experimentally the local scour downstream compound sharp crested V-notch weir. Forty-eight (48 experimental runs were conducted. Three models of weirs with different geometries (combination of notch angles, four upstream water levels, three water levels at the tailgate, and two bed materials were used. Multiple regression equations based on energy principal and dimensional analysis theory were deduced to estimate the local scour downstream of the weir models. The developed equations were compared with the experimental data. The comparison between the local scour downstream classical V-notch weir and a compound sharp-crested weir consisting of two triangular parts with different notch angles was found to be unnoticed. The study recommended using the compound V-notch weir to pass high discharges instead of the classical V-notch weir.

  11. Uncovering Notch pathway in the parasitic flatworm Schistosoma mansoni.

    Science.gov (United States)

    Magalhães, Lizandra G; Morais, Enyara R; Machado, Carla B; Gomes, Matheus S; Cabral, Fernanda J; Souza, Julia M; Soares, Cláudia S; Sá, Renata G; Castro-Borges, William; Rodrigues, Vanderlei

    2016-10-01

    Several signaling molecules that govern development in higher animals have been identified in the parasite Schistosoma mansoni, including the transforming growth factor β, protein tyrosine kinases, nuclear hormone receptors, among others. The Notch pathway is a highly conserved signaling mechanism which is involved in a wide variety of developmental processes including embryogenesis and oogenesis in worms and flies. Here we aimed to provide the molecular reconstitution of the Notch pathway in S. mansoni using the available transcriptome and genome databases. Our results also revealed the presence of the transcripts coded for SmNotch, SmSu(H), SmHes, and the gamma-secretase complex (SmNicastrin, SmAph-1, and SmPen-2), throughout all the life stages analyzed. Besides, it was observed that the viability and separation of adult worm pairs were not affected by treatment with N-[N(3,5)-difluorophenacetyl)-L-Alanyl]-S-phenylglycine t-butyl ester (DAPT), a Notch pathway inhibitor. Moreover, DAPT treatment decreased the production of phenotypically normal eggs and arrested their development in culture. Our results also showed a significant decrease in SmHes transcript levels in both adult worms and eggs treated with DAPT. These results provide, for the first time, functional validation of the Notch pathway in S. mansoni and suggest its involvement in parasite oogenesis and embryogenesis. Given the complexity of the Notch pathway, further experiments shall highlight the full repertoire of Notch-mediated cellular processes throughout the S. mansoni life cycle.

  12. Notch-EGFR/HER2 Bidirectional Crosstalk in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Andrew T Baker

    2014-12-01

    Full Text Available The Notch pathway is a well-established mediator of cell-cell communication that plays a critical role in stem cell survival, self-renewal, cell fate decisions, tumorigenesis, invasion, metastasis, and drug resistance in a variety of cancers. An interesting form of crosstalk exists between the Notch receptor and the Epidermal Growth Factor Receptor Tyrosine Kinase family which consists of HER-1, -2, -3, and -4. Overexpression of HER and/or Notch occurs in several human cancers including brain, lung, breast, ovary, and skin making them potent oncogenes capable of advancing malignant disease. Continued assessment of interplay between these two critical signaling networks uncovers new insight into mechanisms used by HER-driven cancer cells to exploit Notch as a compensatory pathway. The compensatory Notch pathway maintains HER-induced downstream signals transmitted to pathways such as Mitogen Activated Protein Kinase (MAPK and Phosphatidylinositol 3-Kinase (PI3K, thereby allowing cancer cells to survive molecular targeted therapies, undergo EMT, and increase cellular invasion. Uncovering the critical crosstalk between the HER and Notch pathways can lead to improved screening for the expression of these oncogenes enabling patients to optimize their personal treatment options and predict potential treatment resistance. This review will focus on the current state of crosstalk between the HER and Notch receptors and the effectiveness of current therapies targeting HER-driven cancers.

  13. Notch3 drives development and progression of cholangiocarcinoma.

    Science.gov (United States)

    Guest, Rachel V; Boulter, Luke; Dwyer, Benjamin J; Kendall, Timothy J; Man, Tak-Yung; Minnis-Lyons, Sarah E; Lu, Wei-Yu; Robson, Andrew J; Gonzalez, Sofia Ferreira; Raven, Alexander; Wojtacha, Davina; Morton, Jennifer P; Komuta, Mina; Roskams, Tania; Wigmore, Stephen J; Sansom, Owen J; Forbes, Stuart J

    2016-10-25

    The prognosis of cholangiocarcinoma (CC) is dismal. Notch has been identified as a potential driver; forced exogenous overexpression of Notch1 in hepatocytes results in the formation of biliary tumors. In human disease, however, it is unknown which components of the endogenously signaling pathway are required for tumorigenesis, how these orchestrate cancer, and how they can be targeted for therapy. Here we characterize Notch in human-resected CC, a toxin-driven model in rats, and a transgenic mouse model in which p53 deletion is targeted to biliary epithelia and CC induced using the hepatocarcinogen thioacetamide. We find that across species, the atypical receptor NOTCH3 is differentially overexpressed; it is progressively up-regulated with disease development and promotes tumor cell survival via activation of PI3k-Akt. We use genetic KO studies to show that tumor growth significantly attenuates after Notch3 deletion and demonstrate signaling occurs via a noncanonical pathway independent of the mediator of classical Notch, Recombinant Signal Binding Protein for Immunoglobulin Kappa J Region (RBPJ). These data present an opportunity in this aggressive cancer to selectively target Notch, bypassing toxicities known to be RBPJ dependent.

  14. Biological therapy induces expression changes in Notch pathway in psoriasis.

    Science.gov (United States)

    Skarmoutsou, Evangelia; Trovato, Chiara; Granata, Mariagrazia; Rossi, Giulio A; Mosca, Ambra; Longo, Valentina; Gangemi, Pietro; Pettinato, Maurizio; D'Amico, Fabio; Mazzarino, Maria Clorinda

    2015-12-01

    Psoriasis is a chronic inflammatory skin disease, characterized by hyperproliferation of keratinocytes and by skin infiltration of activated T cells. To date, the pathophysiology of psoriasis has not yet been fully elucidated. The Notch pathway plays a determinant role in cell fate determination, proliferation, differentiation, immune cell development and function. Many biological agents, used in the treatment of psoriasis, include TFN-α inhibitors, such as etanercept, adalimumab, and anti IL-12/IL-23 p40 antibody, such as ustekinumab. This study aimed to determine mRNA expression levels by real-time RT-PCR, and protein expression levels, analysed by Western blot and immunohistochemistry, of some components of the Notch pathway, such as NOTCH1, NOTCH2, JAGGED1, and HES1 after biological treatments in psoriatic patients. mRNA and protein levels of NOTCH1, NOTCH2, JAGGED1 and HES1 were upregulated in skin samples from untreated psoriatic patients compared with normal controls. Biological therapy showed to downregulate differently the protein expression levels of the molecules under study. Our study suggests that Notch pathway components might be a potential therapeutic target against psoriasis.

  15. Notch signalling in placental development and gestational diseases.

    Science.gov (United States)

    Haider, S; Pollheimer, J; Knöfler, M

    2017-01-16

    Activation of Notch signalling upon cell-cell contact of neighbouring cells controls a plethora of cellular processes such as stem cell maintenance, cell lineage determination, cell proliferation, and survival. Accumulating evidence suggests that the pathway also critically regulates these events during placental development and differentiation. Herein, we summarize our present knowledge about Notch signalling in murine and human placentation and discuss its potential role in the pathophysiology of gestational disorders. Studies in mice suggest that Notch controls trophectoderm formation, decidualization, placental branching morphogenesis and endovascular trophoblast invasion. In humans, the particular signalling cascade promotes formation of the extravillous trophoblast lineage and regulates trophoblast proliferation, survival and differentiation. Expression patterns as well as functional analyses indicate distinct roles of Notch receptors in different trophoblast subtypes. Altered effects of Notch signalling have been detected in choriocarcinoma cells, consistent with its role in cancer development and progression. Moreover, deregulation of Notch signalling components were observed in pregnancy disorders such as preeclampsia and fetal growth restriction. In summary, Notch plays fundamental roles in different developmental processes of the placenta. Abnormal signalling through this pathway could contribute to the pathogenesis of gestational diseases with aberrant placentation and trophoblast function.

  16. Jet grouting for a groundwater cutoff wall in difficult glacial soil deposits

    Energy Technology Data Exchange (ETDEWEB)

    Flanagan, R.F.; Pepe, F. Jr. [Parsons Brinckerhoff Quade & Douglas, New York, NY (United States)

    1997-12-31

    Jet grouting is being used as part of a groundwater cutoff wall system in a major New York City subway construction project to limit drawdowns in an adjacent PCB contamination plume. A circular test shaft of jet grout columns was conducted during the design phase to obtain wall installation parameters. The test program also included shaft wall mapping, and measurements of; inflows, piezometric levels, ground heave and temperature, and jet grout hydraulic conductivity. An axisymmetric finite element method groundwater model was established to back calculate the in-situ hydraulic conductivities of both the surrounding glacial soils and the jet grout walls by matching observed inflows and piezometric levels. The model also verified the use of packer permeability test as a tool in the field to evaluate the hydraulic conductivities of jet grout columns. Both the test program and analytic studies indicated that adjustments to the construction procedures would be required to obtain lower hydraulic conductivities of the jet grout walls for construction. A comparison is made with the conductivities estimated from the test program/analytic studies with those from the present construction.

  17. Notch reporter activity in breast cancer cell lines identifies a subset of cells with stem cell activity

    OpenAIRE

    D’Angelo, Rosemarie C.; Ouzounova, Maria; Davis, April; Choi, Daejin; Tchuenkam, Stevie M.; Kim, Gwangil; Luther, Tahra; Quraishi, Ahmed A.; Senbabaoglu, Yasin; Conley, Sarah J; Shawn G Clouthier; Hassan, Khaled A.; Wicha, Max S; Korkaya, Hasan

    2015-01-01

    Developmental pathways such as Notch play a pivotal role in tissue specific stem cell self-renewal as well as in tumor development. However, the role of Notch signaling in breast cancer stem cells (CSC) remains to be determined. We utilized a lentiviral Notch reporter system to identify a subset of cells with a higher Notch activity (Notch+) or reduced activity (Notch-) in multiple breast cancer cell lines. Using in vitro and mouse xenotransplantation assays we investigated the role of Notch ...

  18. Modelling of Hydraulic Robot

    DEFF Research Database (Denmark)

    Madsen, Henrik; Zhou, Jianjun; Hansen, Lars Henrik

    1997-01-01

    This paper describes a case study of identifying the physical model (or the grey box model) of a hydraulic test robot. The obtained model is intended to provide a basis for model-based control of the robot. The physical model is formulated in continuous time and is derived by application...... of the laws of physics on the system. The unknown (or uncertain) parameters are estimated with Maximum Likelihood (ML) parameter estimation. The identified model has been evaluated by comparing the measurements with simulation of the model. The identified model was much more capable of describing the dynamics...... of the system than the deterministic model....

  19. HIV Tat Impairs Neurogenesis through Functioning As a Notch Ligand and Activation of Notch Signaling Pathway.

    Science.gov (United States)

    Fan, Yan; Gao, Xiang; Chen, Jinhui; Liu, Ying; He, Johnny J

    2016-11-02

    Alterations in adult neurogenesis have been noted in the brain of HIV-infected individuals and are likely linked to HIV-associated neurocognitive deficits, including those in learning and memory. But the underlying molecular mechanisms are not fully understood. In the study, we took advantage of doxycycline-inducible and astrocyte-specific HIV-1 Tat transgenic mice (iTat) and determined the relationship between Tat expression and neurogenesis. Tat expression in astrocytes was associated with fewer neuron progenitor cells (NPCs), fewer immature neurons, and fewer mature neurons in the dentate gyrus of the hippocampus of the mouse brain. In vitro NPC-derived neurosphere assays showed that Tat-containing conditioned media from astrocytes or recombinant Tat protein inhibited NPC proliferation and migration and altered NPC differentiation, while immunodepletion of Tat from Tat-containing conditioned media or heat inactivation of recombinant Tat abrogated those effects. Notch signaling downstream gene Hes1 promoter-driven luciferase reporter gene assay and Western blotting showed that recombinant Tat or Tat-containing conditioned media activated Hes1 transcription and protein expression, which were abrogated by Tat heat inactivation, immunodepletion, and cysteine mutation at position 30. Last, Notch signaling inhibitor N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT) significantly rescued Tat-impaired NPC differentiation in vitro and neurogenesis in vivo Together, these results show that Tat adversely affects NPCs and neurogenesis through Notch signaling and point to the potential of developing Notch signaling inhibitors as HIV/neuroAIDS therapeutics.

  20. 46 CFR 28.880 - Hydraulic equipment.

    Science.gov (United States)

    2010-10-01

    ... hydraulic equipment and the adjacent work area. Protection shall be afforded to the operator of hydraulic... 46 Shipping 1 2010-10-01 2010-10-01 false Hydraulic equipment. 28.880 Section 28.880 Shipping... INDUSTRY VESSELS Aleutian Trade Act Vessels § 28.880 Hydraulic equipment. (a) Each hydraulic system must...

  1. Strong Coupling between On Chip Notched Ring Resonator and Nanoparticle

    CERN Document Server

    Wang, S; Smith, H; Yi, Y

    2010-01-01

    We have demonstrated a new photonic structure to achieve strong optical coupling between nanoparticle and photonic molecule by utilizing a notched micro ring resonators. By creating a notch in the ring resonator and putting a nanoparticle inside the notch, large spectral shifts and splittings at nm scale can be achieved, compared to only pm scale observed by fiber tip evanescently coupled to the surface of microsphere, thereby significantly lowered the quality factor requirement for single nanoparticle detection. The ability for sorting the type of nanoparticles due to very different mode shift and splitting behavior of dielectric and metallic nanoparticles is also emphasized.

  2. Emerging role of Notch in stem cells and cancer.

    Science.gov (United States)

    Wang, Zhiwei; Li, Yiwei; Banerjee, Sanjeev; Sarkar, Fazlul H

    2009-06-28

    The Notch signaling pathway is known to be responsible for maintaining a balance between cell proliferation and death and, as such, plays important roles in the formation of many types of human tumors. Recently, Notch signaling pathway has been shown to control stem cell self-renewal and multi-potency. As many cancers are thought to be developed from a number of cancer stem-like cells, which are also known to be linked with the acquisition of epithelial-mesenchymal transition (EMT); and thus suggesting an expanding role of Notch signaling in human tumor progression.

  3. Band-notched reconfigurable CPW-fed UWB antenna

    Science.gov (United States)

    Majid, H. A.; Rahim, M. K. A.; Hamid, M. R.; Murad, N. A.; Samsuri, N. A.; Yusof, M. F. M.; Kamarudin, M. R.

    2016-04-01

    A reconfigurable band-notched CPW-fed UWB antenna using electromagnetic bandgap (EBG) structure is proposed. Two structures are positioned adjacent to the transmission line of the UWB antenna. The band-notched characteristic can be disabled by switching the state of switch place at the strip line. The EBG structure produces reconfigurable band notched at 4.0 GHz, which covers C-band satellite communication (3.625-4.2 GHz) systems. The proposed antenna is suitable for UWB systems, which requires reconfigurable band reject function.

  4. Broadband notch filter design for millimeter-wave plasma diagnostics

    DEFF Research Database (Denmark)

    Furtula, Vedran; Michelsen, Poul; Leipold, Frank;

    2010-01-01

    Notch filters are integrated in plasma diagnostic systems to protect millimeter-wave receivers from intensive stray radiation. Here we present a design of a notch filter with a center frequency of 140 GHz, a rejection bandwidth of ∼ 900 MHz, and a typical insertion loss below 2 dB in the passband...... of ±9 GHz. The design is based on a fundamental rectangular waveguide with eight cylindrical cavities coupled by T-junction apertures formed as thin slits. Parameters that affect the notch performance such as physical lengths and conductor materials are discussed. The excited resonance mode...

  5. Study of Water Jet Impulse in Water-Jet Looms

    Institute of Scientific and Technical Information of China (English)

    LI Ke-rang; MA Wei-wei; CHEN Ming

    2005-01-01

    The water jet impulse is brought forward to study the traction force of the water jet to the flying weft in water-jet looms. The distribution of the water jet impulse in the shed is tested by a sensor, and the influence of water jet parameters on the water jet impulse is analyzed.

  6. Chemotherapeutic treatment is associated with Notch1 induction in cutaneous T-cell lymphoma

    DEFF Research Database (Denmark)

    Kamstrup, Maria R; Biskup, Edyta; Manfè, Valentina

    2017-01-01

    level in MyLa2000 and Hut78. Upregulation of well-established Notch targets supported the functional activity of Notch1. Transfection of Notch1 siRNA into MyLa2000 cells was not able to suppress the effects of chemotherapy on Notch1 activation significantly. Notch1 knockdown in combination...... with doxorubicin, etoposide, or gemcitabine compared to chemotherapy alone decreased cell viability by 12, 20, and 26%, respectively (p family members. Our results...

  7. Progressive Damage Modeling of Notched Composites

    Science.gov (United States)

    Aitharaju, Venkat; Aashat, Satvir; Kia, Hamid; Satyanarayana, Arunkumar; Bogert, Philip

    2016-01-01

    There is an increased interest in using non-crimp fabric reinforced composites for primary and secondary structural weight savings in high performance automobile applications. However, one of the main challenges in implementing these composites is the lack of understanding of damage progression under a wide variety of loading conditions for general configurations. Towards that end, researchers at GM and NASA are developing new damage models to predict accurately the progressive failure of these composites. In this investigation, the developed progressive failure analysis model was applied to study damage progression in center-notched and open-hole tension specimens for various laminate schemes. The results of a detailed study with respect to the effect of element size on the analysis outcome are presented.

  8. Deep lateral notch sign and double notch sign in complete tears of the anterior cruciate ligament: MR imaging evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Grimberg, Alexandre [University of California, San Diego School of Medicine, Division of Musculoskeletal Radiology, Department of Radiology, San Diego, CA (United States); Universidade Federal de Sao Paulo, Department of Diagnostic Imaging, Sao Paulo, SP (Brazil); Shirazian, Hoda; Torshizy, Hamid; Smitaman, Edward; Resnick, Donald L. [University of California, San Diego School of Medicine, Division of Musculoskeletal Radiology, Department of Radiology, San Diego, CA (United States); Chang, Eric Y. [Veterans Administrations San Diego Healthcare Systems, Osteoradiology Section, Department of Radiology, San Diego, CA (United States); University of California, San Diego School of Medicine, Division of Musculoskeletal Radiology, Department of Radiology, San Diego, CA (United States)

    2014-11-20

    To systematically compare the notches of the lateral femoral condyle (LFC) in patients with and without complete tears of the anterior cruciate ligament (ACL) in MR studies by (1) evaluating the dimensions of the lateral condylopatellar sulcus; (2) evaluating the presence and appearance of an extra or a double notch and its association with such tears. This retrospective study was approved by our institutional review board, and informed written patient consent was waived. In 58 cases of complete ACL tears and 37 control cases with intact ACL, the number of notches on the LFC was determined, and the depth and anteroposterior (AP) length of each notch were measured in each third of the LFC. The chi-square test, t-test, and logistic regression model were used to analyze demographic data and image findings, as appropriate. Presence of more than one notch demonstrated a sensitivity of 17.2 %, specificity of 100 %, positive predictive value of 100 %, and negative predictive value of 43.5 % for detecting a complete ACL tear. Lateral third depth measurement (p = 0.028) was a significant associated finding with a complete ACL tear. A deep notch in the lateral third of the LFC is a significant associated finding with a complete ACL tear when compared with an ACL-intact control group, and the presence of more than one notch is a specific but insensitive sign of such a tear. (orig.)

  9. Applied hydraulic transients

    CERN Document Server

    Chaudhry, M Hanif

    2014-01-01

    This book covers hydraulic transients in a comprehensive and systematic manner from introduction to advanced level and presents various methods of analysis for computer solution. The field of application of the book is very broad and diverse and covers areas such as hydroelectric projects, pumped storage schemes, water-supply systems, cooling-water systems, oil pipelines and industrial piping systems. Strong emphasis is given to practical applications, including several case studies, problems of applied nature, and design criteria. This will help design engineers and introduce students to real-life projects. This book also: ·         Presents modern methods of analysis suitable for computer analysis, such as the method of characteristics, explicit and implicit finite-difference methods and matrix methods ·         Includes case studies of actual projects ·         Provides extensive and complete treatment of governed hydraulic turbines ·         Presents design charts, desi...

  10. Hydraulic rams; a comparative investigation

    NARCIS (Netherlands)

    Tacke, J.H.P.M.

    1988-01-01

    A mathematical model describing the essential features of hydraulic ram operation is developed in order to clarify the possibilities and limitations of the ram relative to its site and its adjustments. The model distinguishes three different periods in the pumping cycle of the hydraulic ram: acceler

  11. Hydraulics. FOS: Fundamentals of Service.

    Science.gov (United States)

    John Deere Co., Moline, IL.

    This manual on hydraulics is one of a series of power mechanics texts and visual aids for training in the servicing of agricultural and industrial machinery. Focus is on oil hydraulics. Materials provide basic information and illustrations for use by vocational students and teachers as well as shop servicemen and laymen. The twelve chapters focus…

  12. Can Sonography Distinguish a Supraorbital Notch From a Foramen?

    Science.gov (United States)

    Garg, Ravi K; Lee, Kenneth S; Kohn, Sarah C; Baskaya, Mustafa K; Afifi, Ahmed M

    2015-11-01

    Diagnostic tools for evaluating the supraorbital rim in preparation for nerve decompression surgery in patients with chronic headaches are currently limited. We evaluated the use of sonography to diagnose the presence of a supraorbital notch or foramen in 11 cadaver orbits. Sonographic findings were assessed by dissecting cadaver orbits to determine whether a notch or foramen was present. Sonography correctly diagnosed the presence of a supraorbital notch in 7 of 7 cases and correctly diagnosed a supraorbital foramen in 4 of 4 cases. We found that sonography had 100% sensitivity in diagnosing a supraorbital notch and foramen. This tool may therefore be helpful in characterizing the supraorbital rim preoperatively and may influence the decision to use a transpalpebral or endoscopic approach for supraorbital nerve decompression as well as the decision to use local or general anesthesia.

  13. Alpinetin targets glioma stem cells by suppressing Notch pathway.

    Science.gov (United States)

    Wang, Jianpeng; Yan, Zhiyong; Liu, Xia; Che, Shusheng; Wang, Chao; Yao, Weicheng

    2016-07-01

    Glioma is among the most common human malignancies with poor prognosis. Glioma stem cells (GSCs) are the culprit of glioma, suggesting that GSCs are potential therapeutic targets. Notch signaling pathway plays a pivotal role for the function of GSCs, implying that suppression of Notch pathway may be an effective strategy for GSC-targeting therapy. In this study, we found that alpinetin, a natural compound, can suppress the proliferation and invasiveness of GSCs and induce apoptosis in GSCs. Immunoblot analysis and luciferase assay revealed that Notch signaling was suppressed by alpinetin. Furthermore, restoration of Notch signaling activity rescued the effect of alpinetin on GSC's function. The anti-tumor activity of alpinetin was further confirmed in an animal model. Collectively, targeting of GSC by alpinetin is an effective strategy for glioma therapy.

  14. A Compact Printed Quadruple Band-Notched UWB Antenna

    Directory of Open Access Journals (Sweden)

    Xiaoyin Li

    2013-01-01

    Full Text Available A novel compact coplanar waveguide- (CPW- fed ultrawideband (UWB printed planar volcano-smoke antenna (PVSA with four band-notches for various wireless applications is proposed and demonstrated. The low-profile antenna consists of a C-shaped parasitic strip to generate a notched band at 8.01~8.55 GHz for the ITU band, two C-shaped slots, and an inverted U-shaped slot etched in the radiator patch to create three notched bands at 5.15~5.35 GHz, 5.75~5.85 GHz, and 7.25~7.75 GHz for filtering the WLAN and X-band satellite signals. Simulated and measured results both confirm that the proposed antenna has a broad bandwidth of 3.1~12 GHz with VSWR < 2 and good omnidirectional radiation patterns with four notched-bands.

  15. Notch signaling in glioblastoma: a developmental drug target?

    Directory of Open Access Journals (Sweden)

    Boulay Jean-Louis

    2010-11-01

    Full Text Available Abstract Malignant gliomas are among the most devastating tumors for which conventional therapies have not significantly improved patient outcome. Despite advances in imaging, surgery, chemotherapy and radiotherapy, survival is still less than 2 years from diagnosis and more targeted therapies are urgently needed. Notch signaling is central to the normal and neoplastic development of the central nervous system, playing important roles in proliferation, differentiation, apoptosis and cancer stem cell regulation. Notch is also involved in the regulation response to hypoxia and angiogenesis, which are typical tumor and more specifically glioblastoma multiforme (GBM features. Targeting Notch signaling is therefore a promising strategy for developing future therapies for the treatment of GBM. In this review we give an overview of the mechanisms of Notch signaling, its networking pathways in gliomas, and discuss its potential for designing novel therapeutic approaches.

  16. The functional role of Notch signaling in human gliomas

    DEFF Research Database (Denmark)

    Stockhausen, Marie-Thérése; Kristoffersen, Karina; Poulsen, Hans Skovgaard

    2010-01-01

    have been referred to as brain cancer stem cells (bCSC), as they share similarities to normal neural stem cells in the brain. The Notch signaling pathway is involved in cell fate decisions throughout normal development and in stem cell proliferation and maintenance. The role of Notch in cancer is now......Gliomas are among the most devastating adult tumors for which there is currently no cure. The tumors are derived from brain glial tissue and comprise several diverse tumor forms and grades. Recent reports highlight the importance of cancer-initiating cells in the malignancy of gliomas. These cells...... firmly established, and recent data implicate a role for Notch signaling also in gliomas and bCSC. In this review, we explore the role of the Notch signaling pathway in gliomas with emphasis on its role in normal brain development and its interplay with pathways and processes that are characteristic...

  17. A Novel UWB Antenna with Dual Band-Notched Characteristics

    Science.gov (United States)

    Lin, Yongfan; Liang, Jiangang; Wu, Goucheng; Xu, Zhiyong; Niu, Xuebin

    2015-11-01

    In this article, started from analyzing the basic principle of band-notched characteristics, a feasibly method used for band-notched antenna is demonstrated and the equivalent circuit for this method is designed. A novel UWB antenna is designed. Based on this method, two stubs which can be equivalent to shorted stubs in parallel configuration are added to realize dual band-notched characteristics. Simulated and measured results all show that the UWB antenna yields an impendence bandwidth of 2.0-10.6 GHz by defining VSWR ≦ 2, and two obvious band-notched functions (3.27-3.83 GHz, 4.60-5.90 GHz) occur at the working bandwidth of WIMAX (3.3-3.7 GHz) and HiperLAN/2 (5.15-5.35 GHz, 5.47-5.725 GHz), so the electromagnetic interference between UWB application and WIMAX, HiperLAN/2 can be suppressed.

  18. Notch signalling mediates reproductive constraint in the adult worker honeybee

    Science.gov (United States)

    Duncan, Elizabeth J.; Hyink, Otto; Dearden, Peter K.

    2016-01-01

    The hallmark of eusociality is the reproductive division of labour, in which one female caste reproduces, while reproduction is constrained in the subordinate caste. In adult worker honeybees (Apis mellifera) reproductive constraint is conditional: in the absence of the queen and brood, adult worker honeybees activate their ovaries and lay haploid male eggs. Here, we demonstrate that chemical inhibition of Notch signalling can overcome the repressive effect of queen pheromone and promote ovary activity in adult worker honeybees. We show that Notch signalling acts on the earliest stages of oogenesis and that the removal of the queen corresponds with a loss of Notch protein in the germarium. We conclude that the ancient and pleiotropic Notch signalling pathway has been co-opted into constraining reproduction in worker honeybees and we provide the first molecular mechanism directly linking ovary activity in adult worker bees with the presence of the queen. PMID:27485026

  19. Analyzing the posttranslational modification status of Notch using mass spectrometry.

    Science.gov (United States)

    Kakuda, Shinako; Haltiwanger, Robert S

    2014-01-01

    Notch is modified by multiple types of posttranslational modifications, most of which are known to affect Notch function. The extracellular domain (ECD) is modified with N-glycosylation and at least three types of O-glycosylation (O-fucose, O-glucose, and O-GlcNAc), while the intracellular domain is hydroxylated, phosphorylated, and ubiquitinated. In order to analyze the structure and function of the O-glycans decorating the ECD, we have developed semiquantitative mass spectral methods for identifying modifications at individual sites on Notch that are generally applicable to most posttranslational modifications. Here we describe the expression and purification of Notch ECD fragments, digestion of the fragments with proteases to prepare for mass spectral analysis, and identification of peptides modified with O-glycans using mass spectrometry.

  20. Complete Absence of Suprascapular Notch: A Case Report

    Directory of Open Access Journals (Sweden)

    Rohini Mohan Pawar

    2015-10-01

    Full Text Available Suprascapular Nerve Entrapment (SSNE is an acquired neuropathy secondary to compression of suprascapular nerve in the Suprascapular Notch (SSN. Complete ossification of superior transverse scapular ligament may be a cause for suprascapular nerve entrapment. The absence of suprascapular notch is not very common condition, though its prevalence was quoted by Indian authors to be varying from 1.36% to 32.46% in different parts of the country. It is considered to be a predisposing factor for suprascapular nerve entrapment neuropathy. We noticed a male scapula without suprascapular notch in osteology section of Forensic Medicine department. In this case we observed costal and dorsal surfaces of the left scapula of a male without suprascapular notch at its superior border. The details of the said scapula are discussed in this report.

  1. Depinning of domain walls in permalloy nanowires with asymmetric notches

    Science.gov (United States)

    Gao, Y.; You, B.; Ruan, X. Z.; Liu, M. Y.; Yang, H. L.; Zhan, Q. F.; Li, Z.; Lei, N.; Zhao, W. S.; Pan, D. F.; Wan, J. G.; Wu, J.; Tu, H. Q.; Wang, J.; Zhang, W.; Xu, Y. B.; Du, J.

    2016-09-01

    Effective control of the domain wall (DW) motion along the magnetic nanowires is of great importance for fundamental research and potential application in spintronic devices. In this work, a series of permalloy nanowires with an asymmetric notch in the middle were fabricated with only varying the width (d) of the right arm from 200 nm to 1000 nm. The detailed pinning and depinning processes of DWs in these nanowires have been studied by using focused magneto-optic Kerr effect (FMOKE) magnetometer, magnetic force microscopy (MFM) and micromagnetic simulation. The experimental results unambiguously exhibit the presence of a DW pinned at the notch in a typical sample with d equal to 500 nm. At a certain range of 200 nm notch, resulting in two DW depinning fields. Those two depinning fields have opposite d dependences, which may be originated from different potential well/barrier generated by the asymmetric notch with varying d.

  2. Research on hydraulic slotting technology controlling coal-gas outbursts

    Institute of Scientific and Technical Information of China (English)

    WEI Guo-ying; SHAN Zhi-yong; ZHANG Zi-min

    2008-01-01

    Measured to control serious coal-gas outburst in coal seam were analyzed by theory and experimented in test site. A new technique to distress the coal-bed and drain methane, called hydraulic slotting, was described in detail, and the mechanism of hydrau-lic slotting was put forward and analyzed. The characteristic parameter of hydraulic slotting was given in Jiaozuo mining area and the characteristic of validity, adaptability and secu-rity was evaluated. The results show that the stress surrounding the strata and the gas in coal seam is released efficiently and thoroughly while new techniques are taken, as slot-ting at heading face by high pressure large diameter jet. The resistance to coal and gas outbursts is increased dramatically once the area of slotting is increased to a certain size.In the process of driving 2 000 m tunnel by hydraulic slotting excavation, coal and gas outburst never occurre. The technique could be used to prevent and control potential coal-gas outburst in the proceeding of tunnel driving, and the speed tunneling could be as high as more than 2 times.

  3. Competition in notch signaling with cis enriches cell fate decisions.

    Directory of Open Access Journals (Sweden)

    Pau Formosa-Jordan

    Full Text Available Notch signaling is involved in cell fate choices during the embryonic development of Metazoa. Commonly, Notch signaling arises from the binding of the Notch receptor to its ligands in adjacent cells driving cell-to-cell communication. Yet, cell-autonomous control of Notch signaling through both ligand-dependent and ligand-independent mechanisms is known to occur as well. Examples include Notch signaling arising in the absence of ligand binding, and cis-inhibition of Notch signaling by titration of the Notch receptor upon binding to its ligands within a single cell. Increasing experimental evidences support that the binding of the Notch receptor with its ligands within a cell (cis-interactions can also trigger a cell-autonomous Notch signal (cis-signaling, whose potential effects on cell fate decisions and patterning remain poorly understood. To address this question, herein we mathematically and computationally investigate the cell states arising from the combination of cis-signaling with additional Notch signaling sources, which are either cell-autonomous or involve cell-to-cell communication. Our study shows that cis-signaling can switch from driving cis-activation to effectively perform cis-inhibition and identifies under which conditions this switch occurs. This switch relies on the competition between Notch signaling sources, which share the same receptor but differ in their signaling efficiency. We propose that the role of cis-interactions and their signaling on fine-grained patterning and cell fate decisions is dependent on whether they drive cis-inhibition or cis-activation, which could be controlled during development. Specifically, cis-inhibition and not cis-activation facilitates patterning and enriches it by modulating the ratio of cells in the high-ligand expression state, by enabling additional periodic patterns like stripes and by allowing localized patterning highly sensitive to the precursor state and cell-autonomous bistability

  4. Hydraulic Stability of Accropode Armour

    DEFF Research Database (Denmark)

    Jensen, T.; Burcharth, H. F.; Frigaard, Peter

    , and to assess the influence of core permeability on the hydraulic stability of Accropodes. Two structures were examined, one with a relatively permeable core and one with a relatively impermeable core. In November/December 1995, Ph.D.-student Marten Christensen carried out the model tests on the structure...... with permeable core (crushed granite with a gradation of 5-8 mm). The outcome of this study is described in "Hydraulic Stability of Single-Layer Dolos and Accropode Armour Layers" by Christensen & Burcharth (1995). In January/February 1996, Research Assistant Thomas Jensen carried out a similar study......The present report describes the hydraulic model tests of Accropode armour layers carried out at the Hydraulics Laboratory at Aalborg University from November 1995 through March 1996. The objective of the model tests was to investigate the hydraulic stability of Accropode armour layers...

  5. Hydraulic Stability of Accropode Armour

    DEFF Research Database (Denmark)

    Jensen, T.; Burcharth, H. F.; Frigaard, Peter

    , and to assess the influence of core permeability on the hydraulic stability of Accropodes. Two structures were examined, one with a relatively permeable core and one with a relatively impermeable core. In November/December 1995, Ph.D.-student Marten Christensen carried out the model tests on the structure...... with permeable core (crushed granite with a gradation of 5-8 mm). The outcome of this study is described in "Hydraulic Stability of Single-Layer Dolos and Accropode Armour Layers" by Christensen & Burcharth (1995). In January/February 1996, Research Assistant Thomas Jensen carried out a similar study......The present report describes the hydraulic model tests of Accropode armour layers carried out at the Hydraulics Laboratory at Aalborg University from November 1995 through March 1996. The objective of the model tests was to investigate the hydraulic stability of Accropode armour layers...

  6. NOTCH Signaling and ATOH1 in Colorectal Cancers

    OpenAIRE

    2011-01-01

    The Notch receptor signaling pathway regulates expression of the basic helix-loop-helix transcription factor ATOH1 (Math1/Hath1) to determine cell fate in the intestine. In differentiating intestinal stem cells, high levels of Notch activity specify absorptive enterocyte/colonocyte differentiation, whereas high ATOH1 activity specifies secretory (goblet, enteroendocrine, and Paneth) cell differentiation. In colorectal cancer, ATOH1 is a tumor suppressor that is silenced in most tumors, while ...

  7. SIRT1 regulates endothelial Notch signaling in lung cancer.

    Directory of Open Access Journals (Sweden)

    Mian Xie

    Full Text Available BACKGROUND: Sirtuin 1 (SIRT1 acts as a key regulator of vascular endothelial homeostasis, angiogenesis, and endothelial dysfunction. However, the underlying mechanism for SIRT1-mediated lung carcinoma angiogenesis remains unknown. Herein, we report that the nicotinamide adenine dinucleotide 1 (NAD1-dependent deacetylase SIRT1 can function as an intrinsic negative modulator of Delta-like ligand 4 (DLL4/Notch signaling in Lewis lung carcinoma (LLC xenograft-derived vascular endothelial cells (lung cancer-derived ECs. PRINCIPAL FINDINGS: SIRT1 negatively regulates Notch1 intracellular domain (N1IC and Notch1 target genes HEY1 and HEY2 in response to Delta-like ligand 4 (DLL4 stimulation. Furthermore, SIRT1 deacetylated and repressed N1IC expression. Quantitative chromatin immunoprecipitation (qChIP analysis and gene reporter assay demonstrated that SIRT1 bound to one highly conserved region, which was located at approximately -500 bp upstream of the transcriptional start site of Notch1,and repressed Notch1 transcription. Inhibition of endothelial cell growth and sprouting angiogenesis by DLL4/Notch signaling was enhanced in SIRT1-silenced lung cancer-derived EC and rescued by Notch inhibitor DAPT. In vivo, an increase in proangiogenic activity was observed in Matrigel plugs from endothelial-specific SIRT1 knock-in mice. SIRT1 also enhanced tumor neovascularization and tumor growth of LLC xenografts. CONCLUSIONS: Our results show that SIRT1 facilitates endothelial cell branching and proliferation to increase vessel density and promote lung tumor growth through down-regulation of DLL4/Notch signaling and deacetylation of N1IC. Thus, targeting SIRT1 activity or/and gene expression may represent a novel mechanism in the treatment of lung cancer.

  8. The Notched Filtering Characteristics of Stratified Volume Holographic Grating

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Utilizing the tool of beam propagation method(BPM) to calculate the zeroth order diffraction beam intensity,we find SVHG displays notched diffraction response as a function of the readout wavelength.Using the method of SA and considering the variance of refractive index as the readout wavelength changes, a practiced notch filter can be designed and the period of the filter is discussed.

  9. Hydraulic Yaw System

    DEFF Research Database (Denmark)

    Stubkier, Søren; Pedersen, Henrik C.; Mørkholt, M.

    As wind turbines increase in size, combined with increased lifetime demands, new methods for load reduction needs to be examined. One method is to make the yaw system of the turbine soft/flexible and hereby dampen the loads to the system, which is the focus of the current paper. By utilizing...... the HAWC2 aeroelastic code and an extended model of the NREL 5MW turbine combined with a simplified linear model of the turbine, the parameters of the soft yaw system are optimized to reduce loading in critical components. Results shows that a significant reduction in fatigue and extreme loads to the yaw...... system and rotor shaft when utilizing the soft yaw drive concept compared to the original stiff yaw system. The physical demands of the hydraulic yaw system are furthermore examined for a life time of 20 years. Based on the extrapolated loads, the duty cycles show that it is possible to construct...

  10. Electro Hydraulic Hitch Control

    DEFF Research Database (Denmark)

    Hansen, M. R.; Andersen, T. O.; Nielsen, B.

    2003-01-01

    system for agricultural applications and driving for transportation. During tranport phases, the lack of suspension causes the vehicle to bounce and pitch, and makes it difficalt to control. Many systems have been proposed to cope with the oscillatory behavior, and different solutions exist. Common......This paper present and discusses R&D results on electro hydraulic hitch control for off-road vehicle, in particular active damping of oscillation occuring on tractors. The research deals with analysis and control of the oscillations occuring on tractors which are design without any susspection...... for most of the systems are that they operate on the hydrailc actuators generally providing the motive forces for moving the implement and/or attachment, typically a plough. The basic idea and physical working principle are to use the implement, moveable relative to the vehicle, as a damper mass. The paper...

  11. Non-degradative ubiquitination of the Notch1 receptor by the E3 ligase MDM2 activates the Notch signalling pathway.

    Science.gov (United States)

    Pettersson, Susanne; Sczaniecka, Matylda; McLaren, Lorna; Russell, Fiona; Gladstone, Karen; Hupp, Ted; Wallace, Maura

    2013-03-15

    The Notch receptor is necessary for modulating cell fate decisions throughout development, and aberrant activation of Notch signalling has been associated with many diseases, including tumorigenesis. The E3 ligase MDM2 (murine double minute 2) plays a role in regulating the Notch signalling pathway through its interaction with NUMB. In the present study we report that MDM2 can also exert its oncogenic effects on the Notch signalling pathway by directly interacting with the Notch 1 receptor through dual-site binding. This involves both the N-terminal and acidic domains of MDM2 and the RAM [RBP-Jκ (recombination signal-binding protein 1 for Jκ)-associated molecule] and ANK (ankyrin) domains of Notch 1. Although the interaction between Notch1 and MDM2 results in ubiquitination of Notch1, this does not result in degradation of Notch1, but instead leads to activation of the intracellular domain of Notch1. Furthermore, MDM2 can synergize with Notch1 to inhibit apoptosis and promote proliferation. This highlights yet another target for MDM2-mediated ubiquitination that results in activation of the protein rather than degradation and makes MDM2 an attractive target for drug discovery for both the p53 and Notch signalling pathways.

  12. LKB1 and Notch Pathways Interact and Control Biliary Morphogenesis.

    Directory of Open Access Journals (Sweden)

    Pierre-Alexandre Just

    Full Text Available LKB1 is an evolutionary conserved kinase implicated in a wide range of cellular functions including inhibition of cell proliferation, regulation of cell polarity and metabolism. When Lkb1 is inactivated in the liver, glucose homeostasis is perturbed, cellular polarity is affected and cholestasis develops. Cholestasis occurs as a result from deficient bile duct development, yet how LKB1 impacts on biliary morphogenesis is unknown.We characterized the phenotype of mice in which deletion of the Lkb1 gene has been specifically targeted to the hepatoblasts. Our results confirmed that lack of LKB1 in the liver results in bile duct paucity leading to cholestasis. Immunostaining analysis at a prenatal stage showed that LKB1 is not required for differentiation of hepatoblasts to cholangiocyte precursors but promotes maturation of the primitive ductal structures to mature bile ducts. This phenotype is similar to that obtained upon inactivation of Notch signaling in the liver. We tested the hypothesis of a functional overlap between the LKB1 and Notch pathways by gene expression profiling of livers deficient in Lkb1 or in the Notch mediator RbpJκ and identified a mutual cross-talk between LKB1 and Notch signaling. In vitro experiments confirmed that Notch activity was deficient upon LKB1 loss.LKB1 and Notch share a common genetic program in the liver, and regulate bile duct morphogenesis.

  13. Involvement of Notch1/Hes signaling pathway in ankylosing spondylitis.

    Science.gov (United States)

    Xu, Wei; Liang, Chao-Ge; Li, Yi-Fan; Ji, Yun-Han; Qiu, Wen-Jun; Tang, Xian-Zhong

    2015-01-01

    We aimed to investigate the role of Notch1/Hes signaling pathway in the pathogenesis of abnormal ossification of hip ligament in patients with ankylosing spondylitis (AS). 22 AS patients scheduled for artificial hip arthroplasty were randomly chosen as AS group. As controls, we used 4 patients diagnosed with transcervical fracture who underwent hip replacement surgery. Notch1 and Hes mRNA expressions were detected by real-time fluorescent quantitative polymerase chain reaction (RFQ-PCR). Immunohistochemistry (IHC) was used to detect Notch1 and Hes protein expression. Correlation analyses of Notch-l and Hes with AS-related clinical factors were conducted with spearman's correlation analysis and partial correlation analysis. RFQ-PCR results showed significant differences in Notch1 and Hes mRNA expressions between AS group and the control group (all Phip joint ligaments of AS patients, Hes protein expression was associated with the clinical course of AS. Taken together, we suggest that signaling pathways mediated by Notch1-Hes may contribute to ligament ossification of hip joints in AS patients.

  14. Notched K-wire for low thermal damage bone drilling.

    Science.gov (United States)

    Liu, Yao; Belmont, Barry; Wang, Yiwen; Tai, Bruce; Holmes, James; Shih, Albert

    2017-07-01

    The Kirschner wire (K-wire) is a common bone drilling tool in orthopedic surgery to affix fractured bone. Significant heat is produced due to both the cutting and the friction between the K-wire and the bone debris during drilling. Such heat can result in high temperatures, leading to osteonecrosis and other secondary injuries. To reduce thermal injury and other high-temperature associated complications, a new K-wire design with three notches along the three-plane trocar tip fabricated using a thin micro-saw tool is studied. These notches evacuate bone debris and reduce the clogging and heat generation during bone drilling. A set of four K-wires, one without notches and three notched, with depths of 0.5, 0.75, and 1mm, are evaluated. Bone drilling experiments conducted on bovine cortical bone show that notched K-wires could effectively decrease the temperature, thrust force, and torque during bone drilling. K-wires with notches 1mm deep reduced the thrust force and torque by approximately 30%, reduced peak temperatures by 43%, and eliminated blackened burn marks in bone. This study demonstrates that a simple modification of the tip of K-wires can effectively reduce bone temperatures during drilling. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

  15. Radiation-Induced Notch Signaling in Breast Cancer Stem Cells

    Energy Technology Data Exchange (ETDEWEB)

    Lagadec, Chann [Department of Radiation Oncology, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, California (United States); Vlashi, Erina [Department of Radiation Oncology, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, California (United States); Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, California (United States); Alhiyari, Yazeed; Phillips, Tiffany M.; Bochkur Dratver, Milana [Department of Radiation Oncology, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, California (United States); Pajonk, Frank, E-mail: fpajonk@mednet.ucla.edu [Department of Radiation Oncology, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, California (United States); Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, California (United States)

    2013-11-01

    Purpose: To explore patterns of Notch receptor and ligand expression in response to radiation that could be crucial in defining optimal dosing schemes for γ-secretase inhibitors if combined with radiation. Methods and Materials: Using MCF-7 and T47D breast cancer cell lines, we used real-time reverse transcription–polymerase chain reaction to study the Notch pathway in response to radiation. Results: We show that Notch receptor and ligand expression during the first 48 hours after irradiation followed a complex radiation dose–dependent pattern and was most pronounced in mammospheres, enriched for breast cancer stem cells. Additionally, radiation activated the Notch pathway. Treatment with a γ-secretase inhibitor prevented radiation-induced Notch family gene expression and led to a significant reduction in the size of the breast cancer stem cell pool. Conclusions: Our results indicate that, if combined with radiation, γ-secretase inhibitors may prevent up-regulation of Notch receptor and ligand family members and thus reduce the number of surviving breast cancer stem cells.

  16. Notch Fatigue Strength of a PM Disk Superalloy

    Science.gov (United States)

    Gayda, John; Gabb, Timothy P.; Telesman, Jack

    2007-01-01

    New powder metallurgy (PM) disk superalloys, such as ME3, LSHR, and Alloy 10, have been developed in recent years which enable rim temperatures in turbine disk applications to approach 1300 F. Before these alloys can be utilized at 1300 F their long term durability must be ensured. One of the key requirements for disk rims is notch fatigue strength. This issue is extremely important and is a direct result of the blade attachment geometry employed at the disk rim. Further, the imposition of a dwell at maximum load, associated with take off and landing, can also affect notch fatigue strength. For these reasons a study has been undertaken to assess the notch dwell fatigue strength of a modern PM disk alloy through spin pit evaluation of a prototypical disk. The first element of this program involves screening potential heat treatments with respect to notch fatigue strength at 1300 F utilizing a conventional notch fatigue specimen with a stress concentration factor (K(sub t)) of 2 and a 90 sec dwell at peak load. The results of this effort are reported in this paper including the downselect of an optimal heat treatment, from a notch fatigue standpoint.

  17. Botch is a γ-glutamyl Cyclotransferase that Deglycinates and Antagonizes Notch

    Science.gov (United States)

    Chi, Zhikai; Byrne, Sean T.; Dolinko, Andrew; Harraz, Maged M.; Kim, Min-Sik; Umanah, George; Zhong, Jun; Chen, Rong; Zhang, Jianmin; Xu, Jinchong; Chen, Li; Pandey, Akhilesh; Dawson, Ted M.; Dawson, Valina L.

    2014-01-01

    SUMMARY Botch promotes embryonic neurogenesis through inhibition of Notch-1 signaling through inhibition of the initial S1 furin-like cleavage step of Notch maturation. The biochemical process by which Botch inhibits Notch maturation is not known. Here we show that Botch has γ-glutamyl cyclotransferase (GGCT) activity that deglycinates Notch, which prevents the S1 furin-like cleavage. Moreover, Notch is mono-glycinated on the γ-glutamyl carbon of glutamate 1669. The deglycinase activity of Botch is required for inhibition of Notch signaling, both in vitro and in vivo. When the γ-glutamyl-glycine at position 1669 of Notch is degylcinated it is replaced by 5-oxy-proline. These results reveal that Botch regulates Notch signaling through deglycination and identify a novel posttranslational modification of Notch that plays an important role in neurogenesis. PMID:24767995

  18. Jet substructure in ATLAS

    CERN Document Server

    Miller, David W

    2011-01-01

    Measurements are presented of the jet invariant mass and substructure in proton-proton collisions at $\\sqrt{s} = 7$ TeV with the ATLAS detector using an integrated luminosity of 37 pb$^{-1}$. These results exercise the tools for distinguishing the signatures of new boosted massive particles in the hadronic final state. Two "fat" jet algorithms are used, along with the filtering jet grooming technique that was pioneered in ATLAS. New jet substructure observables are compared for the first time to data at the LHC. Finally, a sample of candidate boosted top quark events collected in the 2010 data is analyzed in detail for the jet substructure properties of hadronic "top-jets" in the final state. These measurements demonstrate not only our excellent understanding of QCD in a new energy regime but open the path to using complex jet substructure observables in the search for new physics.

  19. Review of literature on local scour under plane turbulent wall jets

    Science.gov (United States)

    Aamir, Mohammad; Ahmad, Zulfequar

    2016-10-01

    Stability of hydraulic structures is threatened by persistent scour downstream of the apron, which renders their foundations exposed. Jets issuing under the sluice gate are turbulent enough to cause significant scour. Extensive study of the jets is, therefore, necessary in order to understand the underlying hydraulics and provide remedial measures. In this paper, a comprehensive review of the investigations on local scour caused by wall jets is presented, including both the classical as well as the prevalent approach. Various aspects of the scour under wall jets have been explained, including the process of scouring, different parameters affecting the maximum scour depth, analysis of flow characteristics within the scour hole and on the apron, time variation of scour depth, rate of sediment removal, and scour depth estimation formulae.

  20. Heterogeneity of breast cancer stem cells as evidenced with Notch-dependent and Notch-independent populations.

    Science.gov (United States)

    Wong, Nelson K Y; Fuller, Megan; Sung, Sandy; Wong, Fred; Karsan, Aly

    2012-10-01

    Studies have suggested the potential importance of Notch signaling to the cancer stem cell population in some tumors, but it is not known whether all cells in the cancer stem cell fraction require Notch activity. To address this issue, we blocked Notch activity in MCF-7 cells by expressing a dominant-negative MAML-GFP (dnMAML) construct, which inhibits signaling through all Notch receptors, and quantified the effect on tumor-initiating activity. Inhibition of Notch signaling reduced primary tumor sphere formation and side population. Functional quantification of tumor-initiating cell numbers in vivo showed a significant decrease, but not a complete abrogation, of these cells in dnMAML-expressing cells. Interestingly, when assessed in secondary assays in vitro or in vivo, there was no difference in tumor-initiating activity between the dnMAML-expressing cells and control cells. The fact that a subpopulation of dnMAML-expressing cells was capable of forming primary and secondary tumors indicates that there are Notch-independent tumor-initiating cells in the breast cancer cell line MCF-7. Our findings thus provide direct evidence for a heterogeneous cancer stem cell pool, which will require combination therapies against multiple oncogenic pathways to eliminate the tumor-initiating cell population.

  1. Hydraulic conductivity of compacted zeolites.

    Science.gov (United States)

    Oren, A Hakan; Ozdamar, Tuğçe

    2013-06-01

    Hydraulic conductivities of compacted zeolites were investigated as a function of compaction water content and zeolite particle size. Initially, the compaction characteristics of zeolites were determined. The compaction test results showed that maximum dry unit weight (γ(dmax)) of fine zeolite was greater than that of granular zeolites. The γ(dmax) of compacted zeolites was between 1.01 and 1.17 Mg m(-3) and optimum water content (w(opt)) was between 38% and 53%. Regardless of zeolite particle size, compacted zeolites had low γ(dmax) and high w(opt) when compared with compacted natural soils. Then, hydraulic conductivity tests were run on compacted zeolites. The hydraulic conductivity values were within the range of 2.0 × 10(-3) cm s(-1) to 1.1 × 10(-7) cm s(-1). Hydraulic conductivity of all compacted zeolites decreased almost 50 times as the water content increased. It is noteworthy that hydraulic conductivity of compacted zeolite was strongly dependent on the zeolite particle size. The hydraulic conductivity decreased almost three orders of magnitude up to 39% fine content; then, it remained almost unchanged beyond 39%. Only one report was found in the literature on the hydraulic conductivity of compacted zeolite, which is in agreement with the findings of this study.

  2. HYDRODYNAMIC ANALYSIS OF SUCK-IN PULSED JET IN WELL DRILLING

    Institute of Scientific and Technical Information of China (English)

    WANG Rui-he; DU Yu-kun; NI Hong-jian; MA Lin

    2011-01-01

    The development of new drilling methods is important for the exploration and production of oil fields. The pulsed jet is a drilling technology of high potentiality. This article proposes a new concept of suck-in pulsed jet with self-excited oscillation, by which a full use of the hydraulic power can be made in the annular space. A hydrodynamic analysis of suck-in pulsed jet with self-excited oscillation is carried out by numerical simulations and rock-breaking experiments. It is shown that with the jet, a negative pressure zone will be formed in the oscillation cavity to ensure automatic sucking of enough annular fluids and the formation of an efficient pulsed jet. The rock-breaking and pressure testing results have verified the reliability of the numerical simulation. The research provides a basis for the development of the pulsed jet drilling technology.

  3. Numerical simulation of slurry jets using mixture model

    Directory of Open Access Journals (Sweden)

    Wen-xin HUAI

    2013-01-01

    Full Text Available Slurry jets in a static uniform environment were simulated with a two-phase mixture model in which flow-particle interactions were considered. A standard k-ε turbulence model was chosen to close the governing equations. The computational results were in agreement with previous laboratory measurements. The characteristics of the two-phase flow field and the influences of hydraulic and geometric parameters on the distribution of the slurry jets were analyzed on the basis of the computational results. The calculated results reveal that if the initial velocity of the slurry jet is high, the jet spreads less in the radial direction. When the slurry jet is less influenced by the ambient fluid (when the Stokes number St is relatively large, the turbulent kinetic energy k and turbulent dissipation rate ε, which are relatively concentrated around the jet axis, decrease more rapidly after the slurry jet passes through the nozzle. For different values of St, the radial distributions of streamwise velocity and particle volume fraction are both self-similar and fit a Gaussian profile after the slurry jet fully develops. The decay rate of the particle velocity is lower than that of water velocity along the jet axis, and the axial distributions of the centerline particle streamwise velocity are self-similar along the jet axis. The pattern of particle dispersion depends on the Stokes number St. When St = 0.39, the particle dispersion along the radial direction is considerable, and the relative velocity is very low due to the low dynamic response time. When St = 3.08, the dispersion of particles along the radial direction is very little, and most of the particles have high relative velocities along the streamwise direction.

  4. Turbulent buoyant jets and plumes

    CERN Document Server

    Rodi, Wolfgang

    The Science & Applications of Heat and Mass Transfer: Reports, Reviews, & Computer Programs, Volume 6: Turbulent Buoyant Jets and Plumes focuses on the formation, properties, characteristics, and reactions of turbulent jets and plumes. The selection first offers information on the mechanics of turbulent buoyant jets and plumes and turbulent buoyant jets in shallow fluid layers. Discussions focus on submerged buoyant jets into shallow fluid, horizontal surface or interface jets into shallow layers, fundamental considerations, and turbulent buoyant jets (forced plumes). The manuscript then exami

  5. Hydraulic Actuators with Autonomous Hydraulic Supply for the Mainline Aircrafts

    Directory of Open Access Journals (Sweden)

    I. S. Shumilov

    2014-01-01

    Full Text Available Applied in the aircraft control systems, hydraulic servo actuators with autonomous hydraulic supply, so-called, hydraulic actuators of integrated configuration, i.e. combination of a source of hydraulic power and its load in the single unit, are aimed at increasing control system reliability both owing to elimination of the pipelines connecting the actuator to the hydraulic supply source, and owing to avoidance of influence of other loads failure on the actuator operability. Their purpose is also to raise control system survivability by eliminating the long pipeline communications and their replacing for the electro-conductive power supply system, thus reducing the vulnerability of systems. The main reason for a delayed application of the hydraulic actuators in the cutting-edge aircrafts was that such aircrafts require hydraulic actuators of considerably higher power with considerable heat releases, which caused an unacceptable overheat of the hydraulic actuators. Positive and negative sides of the hydraulic actuators, their alternative options of increased reliability and survivability, local hydraulic systems as an advanced alternative to independent hydraulic actuators are considered.Now to use hydraulic actuators in mainline aircrafts is inexpedient since there are the unfairly large number of the problems reducing, first and last, safety of flights, with no essential weight and operational advantages. Still works to create competitive hydraulic actuators ought to be continued.Application of local hydraulic systems (LHS will allow us to reduce length of pressure head and drain pipelines and mass of pipelines, as well as to raise their general fail-safety and survivability. Application of the LHS principle will allow us to use a majority of steering drive advantages. It is necessary to allocate especially the following:- ease of meeting requirements for the non-local spread of the engine weight;- essentially reducing length and weight of

  6. Hydraulic conductivity of organomodified soil

    Energy Technology Data Exchange (ETDEWEB)

    Wallace, R.B.; Grant, J.M.; Voice, T.C.; Rakhshandehroo, G.; Xu, S.; Boyd, S.A. [Michigan State Univ., East Lansing, MI (United States)

    1995-11-01

    The effects of organomodification on soil hydraulic conductivity were investigated. Hydraulic conductivity and porosity of treated and untreated samples of a sandy loam were measured as a function of effective stress. Batch treatment with hexadecyltrimethyl ammonium (HDTMA) and dry packing produced organomodified samples that were 79% less conducive than untreated samples prior to loading. Treated samples lost less hydraulic conductivity as a result of loading than untreated samples so that treated samples had higher conductivity at high loads. Observed differences in conductivity are explained in terms of the role of the treated and untreated clay in controlling initial effective pore size and its change during consolidation.

  7. Design of optical notch filter based on Michelson Gires-Tournois interferometer

    Science.gov (United States)

    Guo, Sen; Zhang, Juan; Li, Xue

    2011-01-01

    Based on digital signal processing theory, a novel method of designing optical notch filter is presented for Michelson interferometer with Gires-Tournois Etalon. The method is not only effective and simple, but also can be used to implement the designing of the optical notch filter which has arbitrary numbers of notch points in one free spectrum range. As a designing example, the optical notch filter with one notch point is given in the paper. The change of output intensity spectrum is also investigated for the reflection coefficient of the mirror and the distance between the mirrors deviating from the ideal value, finally the tuning characteristics of the notch filter is discussed.

  8. NUMERICAL STUDY OF THE NOTCH EFFECT ON THE CREEP BEHAVIOR AND LIFE OF NICKEL-BASE SINGLE CRYSTAL SUPERALLOYS

    Institute of Scientific and Technical Information of China (English)

    Q.M. Yu; Z.F. Yue

    2004-01-01

    Numerical calculations of creep damage development and life behavior of circular notched specimens of nickel-base single crystal had been performed. The creep stress distributions depend on the specimen geometry. For a small notch radius, von Mises stress has an especial distribution. The damage distribution is greatly influenced by the notch depth, notch radius as well as notch type. The creep crack initiation place is different for each notched specimen. The characteristics of notch strengthening and notch weakening depend on the notch radius and notch type. For the same notch type,the creep rupture lives decrease with the decreasing of notch radius. A creep life model has been presented for the multiaxial stress states based on the crystallographic slip system theory.

  9. A Compact Multiband Notch UWB Antenna

    Directory of Open Access Journals (Sweden)

    K. Kumar

    2012-01-01

    Full Text Available A simple and a compact coplanar waveguide (CPW ultrawide band (UWB antenna is presented. Multiband stop function is achieved by two different types of band stop resonators. One is a tilted square spiral slot resonator of different size and length etched on the patch and the other is a coupled resonator etched on the ground plane. These resonators provide considerable increase in notch bandwidth at the stop bands. The proposed antenna has a total size of 18×20.3 mm2. The designed antenna achieves pass band performance at 1.8–2.1 GHz (15.38%, 3.0–3.2 GHz (6.45%, 4.4–4.7 GHz (6.59%, 6.3-6.4 GHz (1.57%, and 8–11.2 GHz (33.33% where VSWR <2 and four stop bands at 2.4–2.8 GHz (15.38%, 3.2–3.7 GHz (14.49%, 5.5–6 GHz (8.69%, and 6.5–7 GHz (7.40% where VSWR is equal to 10. The antenna has a peak gain of 3.8 dBi. The measured results show that the antenna achieves good impedance matching and consistent radiation patterns over an operating bandwidth.

  10. Trastuzumab Resistance: Role for Notch Signaling

    Directory of Open Access Journals (Sweden)

    Kinnari Mehta

    2009-01-01

    Full Text Available Epidermal growth factor receptor-2 (ErbB-2/HER2 is a potent breast oncogene that has been shown to be amplified in 20% of breast cancers. Overexpression of ErbB-2 predicts for aggressive tumor behavior, resistance to some cytotoxic and antihormonal therapies, and poor overall survival. Trastuzumab, the humanized, monoclonal antibody directed against ErbB-2 has shown tremendous efficacy and improved overall survival for women when combined with a taxane-based chemotherapy. However, resistance to trastuzumab remains a major concern, most notably in women with metastatic breast cancer. Numerous mechanisms that include overexpression of alternate receptor tyrosine kinases and/or loss of critical tumor suppressors have been proposed in the last several years to elucidate trastuzumab resistance. Here we review the many possible mechanisms of action that could contribute to resistance, and novel therapies to prevent or reverse the resistant phenotype. Moreover, we provide a critical role for Notch signaling cross-talk with overlapping or new signaling networks in trastuzumab-resistant breast.

  11. Jet Substructure Without Trees

    Energy Technology Data Exchange (ETDEWEB)

    Jankowiak, Martin; Larkoski, Andrew J.; /SLAC /Stanford U., ITP

    2011-08-19

    We present an alternative approach to identifying and characterizing jet substructure. An angular correlation function is introduced that can be used to extract angular and mass scales within a jet without reference to a clustering algorithm. This procedure gives rise to a number of useful jet observables. As an application, we construct a top quark tagging algorithm that is competitive with existing methods. In preparation for the LHC, the past several years have seen extensive work on various aspects of collider searches. With the excellent resolution of the ATLAS and CMS detectors as a catalyst, one area that has undergone significant development is jet substructure physics. The use of jet substructure techniques, which probe the fine-grained details of how energy is distributed in jets, has two broad goals. First, measuring more than just the bulk properties of jets allows for additional probes of QCD. For example, jet substructure measurements can be compared against precision perturbative QCD calculations or used to tune Monte Carlo event generators. Second, jet substructure allows for additional handles in event discrimination. These handles could play an important role at the LHC in discriminating between signal and background events in a wide variety of particle searches. For example, Monte Carlo studies indicate that jet substructure techniques allow for efficient reconstruction of boosted heavy objects such as the W{sup {+-}} and Z{sup 0} gauge bosons, the top quark, and the Higgs boson.

  12. Maintenance of Bone Homeostasis by DLL1-Mediated Notch Signaling.

    Science.gov (United States)

    Muguruma, Yukari; Hozumi, Katsuto; Warita, Hiroyuki; Yahata, Takashi; Uno, Tomoko; Ito, Mamoru; Ando, Kiyoshi

    2016-10-13

    Adult bone mass is maintained through a balance of the activities of osteoblasts and osteoclasts. Although Notch signaling has been shown to maintain bone homeostasis by controlling the commitment, differentiation, and function of cells in both the osteoblast and osteoclast lineages, the precise mechanisms by which Notch performs such diverse and complex roles in bone physiology remain unclear. By using a transgenic approach that modified the expression of delta-like 1 (DLL1) or Jagged1 (JAG1) in an osteoblast-specific manner, we investigated the ligand-specific effects of Notch signaling in bone homeostasis. This study demonstrated for the first time that the proper regulation of DLL1 expression, but not JAG1 expression, in osteoblasts is essential for the maintenance of bone remodeling. DLL1-induced Notch signaling was responsible for the expansion of the bone-forming cell pool by promoting the proliferation of committed but immature osteoblasts. However, DLL1-Notch signaling inhibited further differentiation of the expanded osteoblasts to become fully matured functional osteoblasts, thereby substantially decreasing bone formation. Osteoblast-specific expression of DLL1 did not alter the intrinsic differentiation ability of cells of the osteoclast lineage. However, maturational arrest of osteoblasts caused by the DLL1 transgene impaired the maturation and function of osteoclasts due to a failed osteoblast-osteoclast coupling, resulting in severe suppression of bone metabolic turnover. Taken together, DLL1-mediated Notch signaling is critical for proper bone remodeling as it regulates the differentiation and function of both osteoblasts and osteoclasts. Our study elucidates the importance of ligand-specific activation of Notch signaling in the maintenance of bone homeostasis. This article is protected by copyright. All rights reserved.

  13. Influence of aeration and initial water thickness on axial velocity attenuation of jet flows

    Institute of Scientific and Technical Information of China (English)

    Wang-ru WEI; Jun DENG; Bin LIU

    2013-01-01

    With the development of ski-jump energy dissipation for high and large discharge among the hydraulic projects,the effects of characteristics of water flow on energy dissipation are increasingly important.In the present study,the effects of aeration and the initial water thickness on axial velocity attenuation of jet flow were analyzed,using variance analysis and numerical calculated methods.From the analysis of test data,both of the air concentration and initial water thickness are sensitive factors for the axial velocity attenuation of jet flow along the axial way,and there is no significant interaction effect between the aeration and initial water thickness.Aeration has a more significant effect on the axial velocity attenuation of jet flow.Decreasing the initial water thickness of jet flow can reduce the length of jet core,and make the initial position of axial velocity attenuation closer to the nozzle exit.The numerical calculation results show that aeration can contribute to the enhancement of entrainment ability of jet flow,which may improve the interaction between jet flow and surroundings.For ski-jump energy dissipation among the hydraulic projects,combining aeration with decreasing initial water thickness of jet flow is an effective way to enhance the rate of axial velocity attenuation.

  14. Mutational analysis of NOTCH1, 2, 3 and 4 genes in common solid cancers and acute leukemias.

    Science.gov (United States)

    Lee, Sung Hak; Jeong, Eun Goo; Yoo, Nam Jin; Lee, Sug Hyung

    2007-12-01

    NOTCH proteins (NOTCH1, NOTCH2, NOTCH3 and NOTCH4) play crucial roles in embryonic development. Also, mounting evidence indicates that NOTCH contributes to the pathogenesis of hematopoietic and solid malignancies. Recent studies reported a high incidence of gain-of-function mutations of the NOTCH1 gene in T-cell acute lymphoblastic leukemias (ALL). To see whether NOTCH1 mutation occurs in other malignancies, we analyzed NOTCH1 for the detection of somatic mutations in 334 malignancies, including 48 lung, 48 breast, 48 colorectal and 48 gastric carcinomas, and 142 acute leukemias (105 acute myelogenous leukemias, 32 B-ALLs and 4 T-ALLs) by single-strand conformation polymorphism assay. Also, to see whether other NOTCH genes harbor somatic mutations, we analyzed NOTCH2, NOTCH3 and NOTCH4 genes in the same tissue samples. Overall, we detected three NOTCH mutations in the cancers, which consisted of one NOTCH1 mutation in the T-ALLs (25.0%), one NOTCH2 mutation in the breast carcinomas (2.1%), and one NOTCH3 mutation in the colorectal carcinomas (2.0%). There was no NOTCH mutation in other malignancies analyzed. Our data indicate that NOTCH1 is mutated in T-ALL, but not in other common human cancers, and that NOTCH2, NOTCH3 and NOTH4 genes are rarely mutated in common human cancers. Despite the importance of NOTCH activation in many types of human cancers, mutation of NOTCH genes, except for NOTCH1 mutation in T-ALL, may not play an important role in the tumorigenesis of common cancers.

  15. HYDRAULICS, ATHENS COUNTY, OHIO, USA

    Data.gov (United States)

    Federal Emergency Management Agency, Department of Homeland Security — Hydraulic data include spatial datasets and data tables necessary for documenting the hydrologic procedures for estimating flood discharges for a flood insurance...

  16. HYDRAULICS, JACKSON COUNTY, KENTUCKY, USA

    Data.gov (United States)

    Federal Emergency Management Agency, Department of Homeland Security — Hydraulic data include spatial datasets and data tables necessary for documenting the hydrologic procedures for estimating flood discharges for a flood insurance...

  17. HYDRAULICS, MADISON COUNTY, ALABAMA, USA

    Data.gov (United States)

    Federal Emergency Management Agency, Department of Homeland Security — This Hydraulic data was reviewed and approved by FEMA during the initial MT-2 processing. Recent developments in digital terrain and geospatial database management...

  18. HYDRAULICS, HAMPDEN COUNTY, MA, USA

    Data.gov (United States)

    Federal Emergency Management Agency, Department of Homeland Security — Hydraulic data in this submittal include spatial datasets and model outputs necessary for computation of the 1-percent flooding extent. The minimum requirement for...

  19. Hydraulic wind energy conversion system

    Energy Technology Data Exchange (ETDEWEB)

    1981-07-01

    The purpose of this research was to design, build and test a hydraulic wind energy system. This design used a three bladed turbine, which drove a hydraulic pump. The energy is transmitted from the pump through a long hose and into a hydraulic motor, where the energy is used. This wind system was built and tested during the winter of 1980-1981. The power train included a five meter, three bladed wind turbine, a 9.8:1 ratio gearbox, a 1.44 cubic inch displacement pump with a small supercharge gear pump attached. The hydraulic fluid was pumped through a 70', 3/4'' I-D-high pressure flexhose, then through a volume control valve and into a 1.44 cubic inch displacement motor. The fluid was returned through a 70', 1'' I-D-flexhose.

  20. 14 CFR 29.1435 - Hydraulic systems.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Hydraulic systems. 29.1435 Section 29.1435... STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Equipment Miscellaneous Equipment § 29.1435 Hydraulic systems. (a) Design. Each hydraulic system must be designed as follows: (1) Each element of the hydraulic system...

  1. 14 CFR 23.1435 - Hydraulic systems.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Hydraulic systems. 23.1435 Section 23.1435... § 23.1435 Hydraulic systems. (a) Design. Each hydraulic system must be designed as follows: (1) Each hydraulic system and its elements must withstand, without yielding, the structural loads expected...

  2. 46 CFR 28.405 - Hydraulic equipment.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Hydraulic equipment. 28.405 Section 28.405 Shipping... Operate With More Than 16 Individuals on Board § 28.405 Hydraulic equipment. (a) Each hydraulic system... than four times the system maximum operating pressure. (c) Each hydraulic system must be equipped...

  3. AIP4/Itch regulates Notch receptor degradation in the absence of ligand.

    Directory of Open Access Journals (Sweden)

    Patricia Chastagner

    Full Text Available BACKGROUND: The regulation of Notch signaling heavily relies on ubiquitination events. Drosophila Su(dx, a member of the HECT family of ubiquitin-ligases, has been described as a negative regulator of Notch signaling, acting on the post-endocytic sorting of Notch. The mammalian ortholog of Su(dx, Itch/AIP4, has been shown to have multiple substrates, including Notch, but the precise events regulated by Itch/AIP4 in the Notch pathway have not been identified yet. METHODOLOGY/PRINCIPAL FINDINGS: Using Itch-/- fibroblasts expressing the Notch1 receptor, we show that Itch is not necessary for Notch activation, but rather for controlling the degradation of Notch in the absence of ligand. Itch is indeed required after the early steps of Notch endocytosis to target it to the lysosomes where it is degraded. Furthermore Itch/AIP4 catalyzes Notch polyubiquitination through unusual K29-linked chains. We also demonstrate that although Notch is associated with Itch/AIP4 in cells, their interaction is not detectable in vitro and thus requires either a post-translational modification, or a bridging factor that remains to be identified. CONCLUSIONS/SIGNIFICANCE: Taken together our results identify a specific step of Notch regulation in the absence of any activation and underline differences between mammalian and Drosophila Notch pathways.

  4. Identification of epidermal Pdx1 expression discloses different roles of Notch1 and Notch2 in murine Kras(G12D-induced skin carcinogenesis in vivo.

    Directory of Open Access Journals (Sweden)

    Pawel K Mazur

    Full Text Available BACKGROUND: The Ras and Notch signaling pathways are frequently activated during development to control many diverse cellular processes and are often dysregulated during tumorigenesis. To study the role of Notch and oncogenic Kras signaling in a progenitor cell population, Pdx1-Cre mice were utilized to generate conditional oncogenic Kras(G12D mice with ablation of Notch1 and/or Notch2. METHODOLOGY/PRINCIPAL FINDINGS: Surprisingly, mice with activated Kras(G12D and Notch1 but not Notch2 ablation developed skin papillomas progressing to squamous cell carcinoma providing evidence for Pdx1 expression in the skin. Immunostaining and lineage tracing experiments indicate that PDX1 is present predominantly in the suprabasal layers of the epidermis and rarely in the basal layer. Further analysis of keratinocytes in vitro revealed differentiation-dependent expression of PDX1 in terminally differentiated keratinocytes. PDX1 expression was also increased during wound healing. Further analysis revealed that loss of Notch1 but not Notch2 is critical for skin tumor development. Reasons for this include distinct Notch expression with Notch1 in all layers and Notch2 in the suprabasal layer as well as distinctive p21 and β-catenin signaling inhibition capabilities. CONCLUSIONS/SIGNIFICANCE: Our results provide strong evidence for epidermal expression of Pdx1 as of yet not identified function. In addition, this finding may be relevant for research using Pdx1-Cre transgenic strains. Additionally, our study confirms distinctive expression and functions of Notch1 and Notch2 in the skin supporting the importance of careful dissection of the contribution of individual Notch receptors.

  5. TASI Lectures on Jet Substructure

    CERN Document Server

    Shelton, Jessie

    2013-01-01

    Jet physics is a rich and rapidly evolving field, with many applications to physics in and beyond the Standard Model. These notes, based on lectures delivered at the June 2012 Theoretical Advanced Study Institute, provide an introduction to jets at the Large Hadron Collider. Topics covered include sequential jet algorithms, jet shapes, jet grooming, and boosted Higgs and top tagging.

  6. Jet propagation and deceleration

    CERN Document Server

    Perucho, Manel

    2013-01-01

    Extragalactic jets in active galactic nuclei (AGN) are divided into two morphological types, namely Fanaroff-Riley I (FRI) and Fanaroff-Riley II (FRII). The former show decollimated structure at the kiloparsec scales and are thought to be decelerated by entrainment within the first kiloparsecs of evolution inside the host galaxy. The entrainment and deceleration can be, at least partly, due to the interaction of jets with stellar winds and gas clouds that enter in the jet as they orbit around the galactic centre. In this contribution, I review recent simulations to study the dynamic effect of entrainment from stellar winds in jets and the direct interaction of jets with gas clouds and stellar winds. I also briefly describe the importance of these interactions as a possible scenario of high-energy emission from extragalactic jets.

  7. What ignites optical jets?

    Energy Technology Data Exchange (ETDEWEB)

    Sebastian Jester

    2002-12-23

    The properties of radio galaxies and quasars with and without optical or X-ray jets are compared. The majority of jets from which high-frequency emission has been detected so far (13 with optical emission, 11 with X-rays, 13 with both) are associated with the most powerful radio sources at any given redshift. It is found that optical/X-ray jet sources are more strongly beamed than the average population of extragalactic radio sources. This suggests that the detection or non-detection of optical emission from jets has so far been dominated by surface brightness selection effects, not by jet physics. It implies that optical jets are much more common than is currently appreciated.

  8. Mini-Jet Controlled Turbulent Round Air Jet

    Institute of Scientific and Technical Information of China (English)

    杜诚; 米建春; 周裕; 詹杰

    2011-01-01

    We report an investigation of the active control of a round air jet by multiple radial blowing mini-jets.The Reynolds number based on the jet exit velocity and diameter is 8000.It is found that once the continuous minijets are replaced with pulsed ones,the centerline velocity decay rate K can be greatly increased as the pulsing frequency of mini-jets approaches the natural vortex frequency of the main jet.For example,the K value is amplified by more than 50% with two(or four)pulsed mini-jets blowing,compared with the continuous mini-jets at the same ratio of the mass flow rate of the mini-jets to that of the main jet.%We report an investigation of the active control of a round air jet by multiple radial blowing mini-jets. The Reynolds number based on the jet exit velocity and diameter is 8000. It is found that once the continuous mini-jets are replaced with pulsed ones, the centerline velocity decay rate K can be greatly increased as the pulsing frequency of mini-jets approaches the natural vortex frequency of the main jet. For example, the K value is amplified by more than 50% with two (or four) pulsed mini-jets blowing, compared with the continuous mini-jets at the same ratio of the mass Sow rate of the mini-jets to that of the main jet.

  9. Hotspots, Jets and Environments

    Science.gov (United States)

    Hardcastle, M. J.

    2008-06-01

    I discuss the nature of `hotspots' and `jet knots' in the kpc-scale structures of powerful radio galaxies and their relationship to jet-environment interactions. I describe evidence for interaction between the jets of FRI sources and their local environments, and discuss its relationship to particle acceleration, but the main focus of the paper is the hotspots of FRIIs and on new observational evidence on the nature of the particle acceleration associated with them.

  10. Development and Notch signaling requirements of the zebrafish choroid plexus.

    Directory of Open Access Journals (Sweden)

    Brent R Bill

    Full Text Available BACKGROUND: The choroid plexus (CP is an epithelial and vascular structure in the ventricular system of the brain that is a critical part of the blood-brain barrier. The CP has two primary functions, 1 to produce and regulate components of the cerebral spinal fluid, and 2 to inhibit entry into the brain of exogenous substances. Despite its importance in neurobiology, little is known about how this structure forms. METHODOLOGY AND PRINCIPAL FINDINGS: Here we show that the transposon-mediated enhancer trap zebrafish line Et(Mn16 expresses green fluorescent protein within a population of cells that migrate toward the midline and coalesce to form the definitive CP. We further demonstrate the development of the integral vascular network of the definitive CP. Utilizing pharmacologic pan-notch inhibition and specific morpholino-mediated knockdown, we demonstrate a requirement for Notch signaling in choroid plexus development. We identify three Notch signaling pathway members as mediating this effect, notch1b, deltaA, and deltaD. CONCLUSIONS AND SIGNIFICANCE: This work is the first to identify the zebrafish choroid plexus and to characterize its epithelial and vasculature integration. This study, in the context of other comparative anatomical studies, strongly indicates a conserved mechanism for development of the CP. Finally, we characterize a requirement for Notch signaling in the developing CP. This establishes the zebrafish CP as an important new system for the determination of key signaling pathways in the formation of this essential component of the vertebrate brain.

  11. Enlarged spinoglenoid notch veins causing suprascapular nerve compression

    Energy Technology Data Exchange (ETDEWEB)

    Carroll, Kevin W. [Radiology Regional Center, 700 Goodlette Road, Naples, FL 34102 (United States); Helms, Clyde A. [Duke University Medical Center, Department of Radiology, Box 3808, Durham, NC 27710 (United States); Otte, Michael T. [Invision Medical Imaging and Radiology, 8200 East Belleview Avenue, Suite 124, Greenwood Village, CO 80111 (United States); Moellken, S.M.C. [San Francisco Magnetic Resonance Center, 3333 California Street, Suite 105, San Francisco, CA 94118 (United States); Fritz, R. [National Orthopedic Associates, 1260 South Eliseo Drive, Greenbrae, CA 94904 (United States)

    2003-02-01

    To report the magnetic resonance (MR) imaging findings of enlarged veins in the spinoglenoid notch as a cause of suprascapular nerve compression.Design and patients Six patients presented to MR imaging for evaluation of chronic shoulder pain. Clinical information and MR imaging studies were reviewed. The spinoglenoid notch vascular structures were compared with measurements made in 10 age-matched controls. Spinoglenoid notch vascular structures measured in 10 asymptomatic age-matched control patients ranged from 1 to 4 mm in diameter with an average of 2.2 mm. The six study patients had vascular structures that ranged from 6 to 10 mm in diameter with an average of 8.4 mm. Atrophy and fatty infiltration of the infraspinatus muscle was noted as an associated finding at MR imaging in all six patients. Surgery was performed in three of the six patients, at which time a venous varix was identified in the spinoglenoid notch in all three patients. We describe distended veins in the spinoglenoid notch. These may be readily apparent at MR imaging and should be distinguished from paralabral ganglion cysts compressing the suprascapular nerve in the absence of labral tears, especially if percutaneous aspiration of a ganglion cyst is entertained. (orig.)

  12. Why does necking ignore notches in dynamic tension?

    Directory of Open Access Journals (Sweden)

    Rotbaum Y.

    2015-01-01

    Full Text Available Recent experimental work has revealed that necking of tensile specimens, subjected to dynamic loading, is a deterministic phenomenon, governed by the applied boundary conditions. Furthermore it was shown that the potential sited, dictated by the boundary conditions, may prevail even in the presence of a notch, thus necking may occur away of the notched region. The present paper combines experimental and numerical work to address this issue. Specifically, it is shown that the dynamic tensile failure locus is dictated by both the applied velocity boundary condition and the material mechanical properties, specifically strain-rate sensitivity and strain-rate hardening. It is shown that at sufficiently high impact velocities, the flows stress in the notch vicinity becomes quite higher than in the rest of the specimen, so that while the former resists deformation, it transfers the load to the latter, resulting in the formation of a local neck and failure away from the notch. Small local perturbations in the material properties are shown to be sufficient to stabilize the structure under local failure until a neck forms elsewhere. While the physical observations are quite counterintuitive with respect to the engineering views of stress concentrator's effect, the present work rationalizes those observations and also provides information for the designers of dynamically tensioned structures that may contain notches or similar flaws.

  13. Structural Analysis Uncovers Lipid-Binding Properties of Notch Ligands

    Directory of Open Access Journals (Sweden)

    Chandramouli R. Chillakuri

    2013-11-01

    Full Text Available The Notch pathway is a core cell-cell signaling system in metazoan organisms with key roles in cell-fate determination, stem cell maintenance, immune system activation, and angiogenesis. Signals are initiated by extracellular interactions of the Notch receptor with Delta/Serrate/Lag-2 (DSL ligands, whose structure is highly conserved throughout evolution. To date, no structure or activity has been associated with the extreme N termini of the ligands, even though numerous mutations in this region of Jagged-1 ligand lead to human disease. Here, we demonstrate that the N terminus of human Jagged-1 is a C2 phospholipid recognition domain that binds phospholipid bilayers in a calcium-dependent fashion. Furthermore, we show that this activity is shared by a member of the other class of Notch ligands, human Delta-like-1, and the evolutionary distant Drosophila Serrate. Targeted mutagenesis of Jagged-1 C2 domain residues implicated in calcium-dependent phospholipid binding leaves Notch interactions intact but can reduce Notch activation. These results reveal an important and previously unsuspected role for phospholipid recognition in control of this key signaling system.

  14. Endothelial Notch activity promotes angiogenesis and osteogenesis in bone

    Science.gov (United States)

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

    2014-03-01

    Blood vessel growth in the skeletal system and osteogenesis seem to be coupled, suggesting the existence of molecular crosstalk between endothelial and osteoblastic cells. Understanding the nature of the mechanisms linking angiogenesis and bone formation should be of great relevance for improved fracture healing or prevention of bone mass loss. Here we show that vascular growth in bone involves a specialized, tissue-specific form of angiogenesis. Notch signalling promotes endothelial cell proliferation and vessel growth in postnatal long bone, which is the opposite of the well-established function of Notch and its ligand Dll4 in the endothelium of other organs and tumours. Endothelial-cell-specific and inducible genetic disruption of Notch signalling in mice not only impaired bone vessel morphology and growth, but also led to reduced osteogenesis, shortening of long bones, chondrocyte defects, loss of trabeculae and decreased bone mass. On the basis of a series of genetic experiments, we conclude that skeletal defects in these mutants involved defective angiocrine release of Noggin from endothelial cells, which is positively regulated by Notch. Administration of recombinant Noggin, a secreted antagonist of bone morphogenetic proteins, restored bone growth and mineralization, chondrocyte maturation, the formation of trabeculae and osteoprogenitor numbers in endothelial-cell-specific Notch pathway mutants. These findings establish a molecular framework coupling angiogenesis, angiocrine signals and osteogenesis, which may prove significant for the development of future therapeutic applications.

  15. The Notch pathway in the developing hematopoietic system.

    Science.gov (United States)

    Bigas, Anna; Robert-Moreno, Alex; Espinosa, Lluís

    2010-01-01

    The main function of the Notch signaling pathway is to generate cell diversity during both embryonic development and adult tissue homeostasis. The extended use of this pathway, together with its conservation during evolution, is indicative of its importance. During embryonic development, the vascular and hematopoietic systems are intimately associated and Notch signals are responsible for the correct specification of both systems. More explicitly, Notch is required for the induction of the arterial program; however, it is simultaneously or consecutively also involved in the generation of hematopoietic stem cells. Although both genetic programs are different, they are both implemented in endothelial cells of the dorsal aorta in the midgestation embryo. This close association during the development of arteries and blood has hindered our understanding of Notch function in the generation of hematopoietic stem cells. Here, we will review the work from recent years showing how Notch participates in the embryonic development of hematopoiesis in the mouse, but also in other organisms such as chick, zebrafish and flies.

  16. Oncogenic programmes and Notch activity: an 'organized crime'?

    Science.gov (United States)

    Dominguez, Maria

    2014-04-01

    The inappropriate Notch signalling can influence virtually all aspect of cancer, including tumour-cell growth, survival, apoptosis, angiogenesis, invasion and metastasis, although it does not do this alone. Hence, elucidating the partners of Notch that are active in cancer is now the focus of much intense research activity. The genetic toolkits available, coupled to the small size and short life of the fruit fly Drosophila melanogaster, makes this an inexpensive and effective animal model, suited to large-scale cancer gene discovery studies. The fly eye is not only a non-vital organ but its stereotyped size and disposition also means it is easy to screen for mutations that cause tumours and metastases and provides ample opportunities to test cancer theories and to unravel unanticipated nexus between Notch and other cancer genes, or to discover unforeseen Notch's partners in cancer. These studies suggest that Notch's oncogenic capacity is brought about not simply by increasing signal strength but through partnerships, whereby oncogenes gain more by cooperating than acting individually, as in a ring 'organized crime'.

  17. Suprascapular Notch Asymmetry: A Study on 311 Patients

    Directory of Open Access Journals (Sweden)

    Michał Polguj

    2014-01-01

    Full Text Available The most important risk factor of suprascapular nerve entrapment is probably the shape of the suprascapular notch (SSN. The aim of the study was to perform a radiological study of the symmetry of SSN. Included in the study were 311 patients (137 women and 174 men who underwent standard computed tomography investigation of the chest. A total of 622 computed tomography scans of scapulae were retrospectively analyzed to classify suprascapular notches into five types. Suprascapular notch was recognized as a symmetrical feature in 53.45% of the patients. Symmetry was more frequently seen in females (54.0% versus 52.9%, but not to any significant degree (P=0.8413. Type III was the most commonly noted symmetrical feature (66.9% and type II was less common (0.6%. Type III was the most symmetrical type of suprascapular notch, occurring significantly more often as a symmetrical feature in comparison with type I (P<0.0001, type II (P=0.00137, or type IV (P=0.001. Our investigation did not show that the suprascapular notch is a symmetrical feature. However, symmetry was recognized more frequently in the case of type III SSN. No significant differences in symmetry were found with regard to sex.

  18. IKKα activation of NOTCH links tumorigenesis via FOXA2 suppression.

    Science.gov (United States)

    Liu, Mo; Lee, Dung-Fang; Chen, Chun-Te; Yen, Chia-Jui; Li, Long-Yuan; Lee, Hong-Jen; Chang, Chun-Ju; Chang, Wei-Chao; Hsu, Jung-Mao; Kuo, Hsu-Ping; Xia, Weiya; Wei, Yongkun; Chiu, Pei-Chun; Chou, Chao-Kai; Du, Yi; Dhar, Debanjan; Karin, Michael; Chen, Chung-Hsuan; Hung, Mien-Chie

    2012-01-27

    Proinflammatory cytokine TNFα plays critical roles in promoting malignant cell proliferation, angiogenesis, and tumor metastasis in many cancers. However, the mechanism of TNFα-mediated tumor development remains unclear. Here, we show that IKKα, an important downstream kinase of TNFα, interacts with and phosphorylates FOXA2 at S107/S111, thereby suppressing FOXA2 transactivation activity and leading to decreased NUMB expression, and further activates the downstream NOTCH pathway and promotes cell proliferation and tumorigenesis. Moreover, we found that levels of IKKα, pFOXA2 (S107/111), and activated NOTCH1 were significantly higher in hepatocellular carcinoma tumors than in normal liver tissues and that pFOXA2 (S107/111) expression was positively correlated with IKKα and activated NOTCH1 expression in tumor tissues. Therefore, dysregulation of NUMB-mediated suppression of NOTCH1 by TNFα/IKKα-associated FOXA2 inhibition likely contributes to inflammation-mediated cancer pathogenesis. Here, we report a TNFα/IKKα/FOXA2/NUMB/NOTCH1 pathway that is critical for inflammation-mediated tumorigenesis and may provide a target for clinical intervention in human cancer.

  19. The National Shipbuilding Research Origran, Oriceedubgs if tge REAPS Technical Symposium. Paper No. 2e: Application of Water Jet Technology to Shipbuilding

    Science.gov (United States)

    1977-06-01

    Proceedings of the REAPS Technical Symposium. Paper No. 23: Applications of Water Jet Technology to Shipbuilding. The use of hydraulic techniques for...ship hull cleaning/surface preparation and cutting of primary metals has received considerable attention in recent years. Water jet cleaning of ship

  20. Properties of gluon jets

    Energy Technology Data Exchange (ETDEWEB)

    Sugano, K.

    1986-09-01

    The properties of gluon jets are reviewed from an experimental point of view. The measured characteristics are compared to theoretical expectations. Although neither data nor models for the gluon jets are in the mature stage, there are remarkable agreements and also intriguing disagreements between experiment and theory. Since much interesting data have begun to emerge from various experiments and the properties of gluon jets are deeply rooted in the basic structure of non-Abelian gauge theory, the study of gluon jets casts further light on our understanding of QCD. Finally, the future prospects are discussed.

  1. The hydrogen laminar jet

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez-Sanz, M. [Departamento de Motopropulsion y Termofluidomecanica, ETSI Aeronauticos, Universidad Politecnica de Madrid, 28040 Madrid (Spain); Rosales, M. [Department Ingenieria Termica y de Fluidos, Universidad Carlos III de Madrid, 28911, Leganes (Spain); Instituto de Innovacion en Mineria y Metalurgia, Avenida del Valle 738, Santiago (Chile); Sanchez, A.L. [Department Ingenieria Termica y de Fluidos, Universidad Carlos III de Madrid, 28911, Leganes (Spain)

    2010-04-15

    Numerical and asymptotic methods are used to investigate the structure of the hydrogen jet discharging into a quiescent air atmosphere. The analysis accounts in particular for the variation of the density and transport properties with composition. The Reynolds number of the flow R{sub j}, based on the initial jet radius a, the density {rho}{sub j} and viscosity {mu}{sub j} of the jet and the characteristic jet velocity u{sub j}, is assumed to take moderately large values, so that the jet remains slender and stable, and can be correspondingly described by numerical integration of the continuity, momentum and species conservation equations written in the boundary-layer approximation. The solution for the velocity and composition in the jet development region of planar and round jets, corresponding to streamwise distances of order R{sub j}a, is computed numerically, along with the solutions that emerge both in the near field and in the far field. The small value of the hydrogen-to-air molecular weight ratio is used to simplify the solution by considering the asymptotic limit of vanishing jet density. The development provides at leading-order explicit analytical expressions for the far-field velocity and hydrogen mass fraction that describe accurately the hydrogen jet near the axis. The information provided can be useful in particular to characterize hydrogen discharge processes from holes and cracks. (author)

  2. Technologies and Innovations for Hydraulic Pumps

    OpenAIRE

    Ivantysynova, Monika

    2016-01-01

    Positive displacement machines working as hydraulic pumps or hydraulic motors have always been, are and will be an essential part of any hydraulic system. Current trends and future demands on energy efficient systems will not only drastically increase the number of positive displacement machines needed for modern efficient hydraulic circuits but will significantly change the performance requirements of pumps and motors. Throttleless system configurations will change the landscape of hydraulic...

  3. Notch Ligand Endocytosis Generates Mechanical Pulling Force Dependent on Dynamin, Epsins and Actin

    Science.gov (United States)

    Meloty-Kapella, Laurence; Shergill, Bhupinder; Kuon, Jane; Botvinick, Elliot; Weinmaster, Gerry

    2012-01-01

    SUMMARY Notch signaling induced by cell surface ligands is critical to development and maintenance of many eukaryotic organisms. Notch and its ligands are integral membrane proteins that facilitate direct cell-cell interactions to activate Notch proteolysis and release the intracellular domain that directs Notch-specific cellular responses. Genetic studies suggest Notch ligands require endocytosis, ubiquitylation and epsin endocytic adaptors to activate signaling, yet the exact role ligand endocytosis serves remains unresolved. Here we characterize a molecularly distinct mode of clathrin-mediated endocytosis requiring ligand ubiquitylation, epsins and actin for ligand cells to activate signaling in Notch cells. Using a cell-bead optical tweezers system, we obtained evidence for cell-mediated mechanical force dependent on this distinct mode of ligand endocytosis. We propose mechanical pulling force produced by endocytosis of Notch-bound ligand drives conformational changes in Notch that permit activating proteolysis. PMID:22658936

  4. Activation of the Notch signaling pathway promotes neurovascular repair after traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Qi-shan Ran

    2015-01-01

    Full Text Available The Notch signaling pathway plays a key role in angiogenesis and endothelial cell formation, but it remains unclear whether it is involved in vascular repair by endothelial progenitor cells after traumatic brain injury. Therefore, in the present study, we controlled the Notch signaling pathway using overexpression and knockdown constructs. Activation of the Notch signaling pathway by Notch1 or Jagged1 overexpression enhanced the migration, invasiveness and angiogenic ability of endothelial progenitor cells. Suppression of the Notch signaling pathway with Notch1 or Jagged1 siRNAs reduced the migratory capacity, invasiveness and angiogenic ability of endothelial progenitor cells. Activation of the Notch signaling pathway in vivo in a rat model of mild traumatic brain injury promoted neurovascular repair. These findings suggest that the activation of the Notch signaling pathway promotes blood vessel formation and tissue repair after brain trauma.

  5. Botch Is a γ-Glutamyl Cyclotransferase that Deglycinates and Antagonizes Notch

    Directory of Open Access Journals (Sweden)

    Zhikai Chi

    2014-05-01

    Full Text Available Botch promotes embryonic neurogenesis by inhibiting the initial S1 furin-like cleavage step of Notch maturation. The biochemical process by which Botch inhibits Notch maturation is not known. Here, we show that Botch has γ-glutamyl cyclotransferase (GGCT activity that deglycinates Notch, which prevents the S1 furin-like cleavage. Moreover, Notch is monoglycinated on the γ-glutamyl carbon of glutamate 1,669. The deglycinase activity of Botch is required for inhibition of Notch signaling both in vitro and in vivo. When the γ-glutamyl-glycine at position 1,669 of Notch is degylcinated, it is replaced by 5-oxy-proline. These results reveal that Botch regulates Notch signaling through deglycination and identify a posttranslational modification of Notch that plays an important role in neurogenesis.

  6. Notch signalling in primary cutaneous CD30+ lymphoproliferative disorders: a new therapeutic approach?

    DEFF Research Database (Denmark)

    Kamstrup, M R; Biskup, E; Gniadecki, R

    2010-01-01

    The oncogenic potential of deregulated Notch signalling has been described in several haematopoietic malignancies. We have previously reported an increased expression of Notch1 in primary cutaneous CD30+ lymphoproliferative disorders, lymphomatoid papulosis and primary cutaneous anaplastic large-...

  7. Activation of the Notch signaling pathway promotes neurovascular repair after traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Qi-shan Ran; Yun-hu Yu; Xiao-hong Fu; Yuan-chao Wen

    2015-01-01

    The Notch signaling pathway plays a key role in angiogenesis and endothelial cell formation, but it remains unclear whether it is involved in vascular repair by endothelial progenitor cells after traumatic brain injury. Therefore, in the present study, we controlled the Notch signaling path-way using overexpression and knockdown constructs. Activation of the Notch signaling pathway by Notch1 or Jagged1 overexpression enhanced the migration, invasiveness and angiogenic ability of endothelial progenitor cells. Suppression of the Notch signaling pathway with Notch1 or Jagged1 siRNAs reduced the migratory capacity, invasiveness and angiogenic ability of endo-thelial progenitor cells. Activation of the Notch signaling pathwayin vivo in a rat model of mild traumatic brain injury promoted neurovascular repair. These ifndings suggest that the activation of the Notch signaling pathway promotes blood vessel formation and tissue repair after brain trauma.

  8. [Research Progress on Notch Signal Pathway in Acute Graft-Versus-Host Disease -Review].

    Science.gov (United States)

    Guo, Dong-Mei; Li, Ban-Ban; Li, Chun-Pu; Teng, Qing-Liang

    2017-02-01

    The Notch signaling pathway is a highly conserved cell signaling system that plays an essential role in many biological processes. Notch signaling regulates multiple aspects of hematopoiesis, especially during T cell develop-ment. Recent data suggest that Notch also regulates mature T cell differentiation and function. The latest data show that Notch also plays an essential role in alloreactive T cells mediating acute graft-versus-host disease (aGVHD), the most severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Notch inhibition in donor-derived T cells or blockade of individual Notch ligands and receptors after transplantation can reduce GVHD severity and mortality in mouse models of allo-HSCT, without causing global immunosuppression. These findings indicate Notch in T cells as an attractive therapeutic target to control aGVHD. In this article, the pathophysiology of aGVHD, the Notch signal pathway and aGVHD are reviewed.

  9. Notch signaling stimulates osteogenic differentiation of human bone marrow-derived mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    LU Zhuozhuang; WU Zuze(WU Chutse); ZHANG Qunwei; WANG Hua; JIA Xiangxu; DUAN Haifeng; WANG Lisheng

    2004-01-01

    Notch signaling is one of the most important pathways mediating cell determination and differentiation. In this study, the roles of Notch signal in the regulation of osteogenic differentiation of human bone marrow mesenchymal stem cells (hMSCs) were investigated. The expression of Notch1, Jagged1 and DTX1 detected by reverse transcription polymerase chain reaction (RT-PCR) suggested that Notch signal might exhibit a physiological regulatory role in the differentiation of MSCs. Constitutive expression of the intracellular domain of Notch1 (ICN), the active form of Notch1 protein, can activate Notch signal in cells without ligands' binding. hMSCs were isolated, expanded, and infected with retrovirus carrying green fluorescent protein (GFP) gene or ICN. Overexpression of ICN in hMSCs resulted in enhanced osteogenic differentiation induced by dexamethasone (Dex), which was characterized by an increase of cellular alkaline phosphatase (ALP) activity and calcium deposition. These results indicate that Notch stimulates differentiation of MSCs into osteoblasts.

  10. Notch signalling in primary cutaneous CD30+ lymphoproliferative disorders: a new therapeutic approach?

    DEFF Research Database (Denmark)

    Kamstrup, M R; Biskup, E; Gniadecki, R

    2010-01-01

    The oncogenic potential of deregulated Notch signalling has been described in several haematopoietic malignancies. We have previously reported an increased expression of Notch1 in primary cutaneous CD30+ lymphoproliferative disorders, lymphomatoid papulosis and primary cutaneous anaplastic large...

  11. Prospects for application of robotic mechano-hydraulical excavation of gas-bearing coal layers at great depths

    Science.gov (United States)

    Fryanov, V. N.; Pavlova, L. D.

    2016-10-01

    In the paper the scientific basis for robotic technology of excavation prone to gas- dynamic phenomena of a coal layer with high gas-bearing capacity at great depths is developed. The constructive scheme of automated remote-controlled mining robot, that fractures coal by high-pressure hydraulic jets in the gas polluted environment, is proposed.

  12. Jet mass spectra in Higgs+one jet at NNLL

    Energy Technology Data Exchange (ETDEWEB)

    Jouttenus, Teppo T.; Stewart, Iain W. [Massachusetts Institute of Technology, Cambridge, MA (United States). Center for Theoretical Physics; Tackmann, Frank J. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Waalewijn, Wouter J. [California Univ., San Diego, La Jolla, CA (United States). Dept. of Physics

    2013-02-15

    The invariant mass of a jet is a benchmark variable describing the structure of jets at the LHC. We calculate the jet mass spectrum for Higgs plus one jet at the LHC at next-to-next-to-leading logarithmic (NNLL) order using a factorization formula. At this order, the cross section becomes sensitive to perturbation theory at the soft m{sup 2}{sub jet}/p{sup jet}{sub T} scale. Our calculation is exclusive and uses the 1-jettiness global event shape to implement a veto on additional jets. The dominant dependence on the jet veto is removed by normalizing the spectrum, leaving residual dependence from non-global logarithms depending on the ratio of the jet mass and jet veto variables. For our exclusive jet cross section these non-global logarithms are parametrically smaller than in the inclusive case, allowing us to obtain a complete NNLL result. Results for the dependence of the jet mass spectrum on the kinematics, jet algorithm, and jet size R are given. Using individual partonic channels we illustrate the difference between the jet mass spectra for quark and gluon jets. We also study the effect of hadronization and underlying event on the jet mass in Pythia. To highlight the similarity of inclusive and exclusive jet mass spectra, a comparison to LHC data is presented.

  13. Dynamics of Water Jet in Water Jet Looms

    Institute of Scientific and Technical Information of China (English)

    李克让; 陈明

    2001-01-01

    On the base of the study on dynamics of water jet in water jet looms, the parameters of water jet mechanism which affect the speed of water jet are analyzed and optimized. So the stability of the water jet can be improved to raise the speed of water jet as well as weft insertion rate and to enlarge the width of woven fabrics a lot. At the same time it also points out that to increase water jet speed and to prolong its affective jet time depend mainly on the accretion of spring rate (constant)of stiffness and the diminution of plunger's cross sectional area respectively.

  14. Notch receptor expression in neurogenic regions of the adult zebrafish brain.

    Directory of Open Access Journals (Sweden)

    Vanessa de Oliveira-Carlos

    Full Text Available The adult zebrash brain has a remarkable constitutive neurogenic capacity. The regulation and maintenance of its adult neurogenic niches are poorly understood. In mammals, Notch signaling is involved in stem cell maintenance both in embryonic and adult CNS. To better understand how Notch signaling is involved in stem cell maintenance during adult neurogenesis in zebrafish we analysed Notch receptor expression in five neurogenic zones of the adult zebrafish brain. Combining proliferation and glial markers we identified several subsets of Notch receptor expressing cells. We found that 90 [Formula: see text] of proliferating radial glia express notch1a, notch1b and notch3. In contrast, the proliferating non-glial populations of the dorsal telencephalon and hypothalamus rarely express notch3 and about half express notch1a/1b. In the non-proliferating radial glia notch3 is the predominant receptor throughout the brain. In the ventral telencephalon and in the mitotic area of the optic tectum, where cells have neuroepithelial properties, notch1a/1b/3 are expressed in most proliferating cells. However, in the cerebellar niche, although progenitors also have neuroepithelial properties, only notch1a/1b are expressed in a high number of PCNA [Formula: see text] cells. In this region notch3 expression is mostly in Bergmann glia and at low levels in few PCNA [Formula: see text] cells. Additionally, we found that in the proliferation zone of the ventral telencephalon, Notch receptors display an apical high to basal low gradient of expression. Notch receptors are also expressed in subpopulations of oligodendrocytes, neurons and endothelial cells. We suggest that the partial regional heterogeneity observed for Notch expression in progenitor cells might be related to the cellular diversity present in each of these neurogenic niches.

  15. Activation of the Notch signaling pathway promotes neurovascular repair after traumatic brain injury

    OpenAIRE

    2015-01-01

    The Notch signaling pathway plays a key role in angiogenesis and endothelial cell formation, but it remains unclear whether it is involved in vascular repair by endothelial progenitor cells after traumatic brain injury. Therefore, in the present study, we controlled the Notch signaling pathway using overexpression and knockdown constructs. Activation of the Notch signaling pathway by Notch1 or Jagged1 overexpression enhanced the migration, invasiveness and angiogenic ability of endothelial pr...

  16. Mesoporous Silica Nanoparticles as Drug Delivery Systems for Targeted Inhibition of Notch Signaling in Cancer

    OpenAIRE

    2011-01-01

    Notch signaling, a key regulator of stem cells, is frequently overactivated in cancer. It is often linked to aggressive forms of cancer, evading standard treatment highlighting Notch as an exciting therapeutic target. Notch is in principle “druggable” by γ-secretase inhibitors (GSIs), inhibitory peptides and antibodies, but clinical use of Notch inhibitors is restricted by severe side effects and there is a demand for alternative cancer-targeted therapy. Here, we present a novel approach, usi...

  17. Roles of Pofut1 and O-fucose in mammalian Notch signaling.

    Science.gov (United States)

    Stahl, Mark; Uemura, Kazuhide; Ge, Changhui; Shi, Shaolin; Tashima, Yuko; Stanley, Pamela

    2008-05-16

    Mammalian Notch receptors contain 29-36 epidermal growth factor (EGF)-like repeats that may be modified by protein O-fucosyltransferase 1 (Pofut1), an essential component of the canonical Notch signaling pathway. The Drosophila orthologue Ofut1 is proposed to function as both a chaperone required for stable cell surface expression of Notch and a protein O-fucosyltransferase. Here we investigate these dual roles of Pofut1 in relation to endogenous Notch receptors of Chinese hamster ovary and murine embryonic stem (ES) cells. We show that fucosylation-deficient Lec13 Chinese hamster ovary cells have wild type levels of Pofut1 and cell surface Notch receptors. Nevertheless, they have reduced binding of Notch ligands and low levels of Delta1- and Jagged1-induced Notch signaling. Exogenous fucose but not galactose rescues both ligand binding and Notch signaling. Murine ES cells lacking Pofut1 also have wild type levels of cell surface Notch receptors. However, Pofut1-/- ES cells do not bind Notch ligands or exhibit Notch signaling. Although overexpression of fucosyltransferase-defective Pofut1 R245A in Pofut1-/- cells partially rescues ligand binding and Notch signaling, this effect is not specific. The same rescue is achieved by an unrelated, inactive, endoplasmic reticulum glucosidase. Therefore, mammalian Notch receptors require Pofut1 for the generation of optimally functional Notch receptors, but, in contrast to Drosophila, Pofut1 is not required for stable cell surface expression of Notch. Importantly, we also show that, under certain circumstances, mammalian Notch receptors are capable of signaling in the absence of Pofut1 and O-fucose.

  18. Hyper-activation of Notch3 amplifies the proliferative potential of rhabdomyosarcoma cells.

    Directory of Open Access Journals (Sweden)

    Maria De Salvo

    Full Text Available Rhabdomyosarcoma (RMS is a pediatric myogenic-derived soft tissue sarcoma that includes two major histopathological subtypes: embryonal and alveolar. The majority of alveolar RMS expresses PAX3-FOXO1 fusion oncoprotein, associated with the worst prognosis. RMS cells show myogenic markers expression but are unable to terminally differentiate. The Notch signaling pathway is a master player during myogenesis, with Notch1 activation sustaining myoblast expansion and Notch3 activation inhibiting myoblast fusion and differentiation. Accordingly, Notch1 signaling is up-regulated and activated in embryonal RMS samples and supports the proliferation of tumor cells. However, it is unable to control their differentiation properties. We previously reported that Notch3 is activated in RMS cell lines, of both alveolar and embryonal subtype, and acts by inhibiting differentiation. Moreover, Notch3 depletion reduces PAX3-FOXO1 alveolar RMS tumor growth in vivo. However, whether Notch3 activation also sustains the proliferation of RMS cells remained unclear. To address this question, we forced the expression of the activated form of Notch3, Notch3IC, in the RH30 and RH41 PAX3-FOXO1-positive alveolar and in the RD embryonal RMS cell lines and studied the proliferation of these cells. We show that, in all three cell lines tested, Notch3IC over-expression stimulates in vitro cell proliferation and prevents the effects of pharmacological Notch inhibition. Furthermore, Notch3IC further increases RH30 cell growth in vivo. Interestingly, knockdown of Notch canonical ligands JAG1 or DLL1 in RMS cell lines decreases Notch3 activity and reduces cell proliferation. Finally, the expression of Notch3IC and its target gene HES1 correlates with that of the proliferative marker Ki67 in a small cohort of primary PAX-FOXO1 alveolar RMS samples. These results strongly suggest that high levels of Notch3 activation increase the proliferative potential of RMS cells.

  19. Digital notch filter based active damping for LCL filters

    DEFF Research Database (Denmark)

    Yao, Wenli; Yang, Yongheng; Zhang, Xiaobin

    2015-01-01

    . In contrast, the active damping does not require any dissipation elements, and thus has become of increasing interest. As a result, a vast of active damping solutions have been reported, among which multi-loop control systems and additional sensors are necessary, leading to increased cost and complexity....... In this paper, a notch filter based active damping without the requirement of additional sensors is proposed, where the inverter current is employed as the feedback variable. Firstly, a design method of the notch filter for active damping is presented. The entire system stability has then been investigated...... in the z-domain. Simulations and experiments are carried out to verify the proposed active damping method. Both results have confirmed that the notch filter based active damping can ensure the entire system stability in the case of resonances with a good system performance....

  20. The Notch pathway: a novel target for myocardial remodelling therapy?

    Science.gov (United States)

    Ferrari, Roberto; Rizzo, Paola

    2014-08-21

    Pathological ventricle remodelling, which follows a cardiac insult, causes heart failure. Despite the existence of multiple pharmaceutical approaches, heart failure is one of the leading causes of death worldwide and there is an urgent need to explore new therapeutic avenues. The Notch pathway is an evolutionary conserved fundamental pathway that regulates cell fate during development as well as throughout postnatal life in self-renewing tissues. In the myocardium, Notch signalling is involved in the modulation of cardiomyocytes survival, cardiac stem cells differentiation, and angiogenesis which are factors known to determine the extent of pathological cardiac remodelling. Modulation of the Notch pathway could become a tool to limit ventricle remodelling and the associated inexorable deterioration of cardiac performance.

  1. The notch effect on fracture of polyurethane materials

    Directory of Open Access Journals (Sweden)

    T. Voiconi

    2014-10-01

    Full Text Available This paper investigates the fracture properties and notch effect of PUR materials with four different densities. The asymmetric semi-circular bend specimen was adapted to perform mixed mode fracture toughness tests. This semi-circular specimen with radius R, which contains an edge crack of length a oriented normal to the specimen edge, loaded with a three point bending fixture, was proved to give wide range of mixed modes from pure mode I to pure mode II, only by changing the position of one support. Different types of notched specimens were considered for notch effect investigations and the Theory of Critical Distances was applied. It could be seen that the critical distances are influenced by the cellular structure of investigated materials

  2. Planar Ultrawideband Antenna with Photonically Controlled Notched Bands

    Directory of Open Access Journals (Sweden)

    Drasko Draskovic

    2013-01-01

    Full Text Available A design of a planar microstrip-fed ultrawideband (UWB printed circular monopole antenna with optically controlled notched bands is presented. The proposed antenna is composed of a circular ultrawideband patch, with an etched T-shaped slot controlled by an integrated silicon switch. The slot modifies the frequency response of the antenna suppressing 3.5–5 GHz band when the switch is in open state. The optical switch is controlled by a low-power near-infrared (808 nm laser diode, which causes the change in the frequency response of the antenna generating a frequency notch. This solution could be expanded to include several notches in the antenna frequency response achieving a fully reconfigurable UWB antenna. The antenna could be remotely controlled at large distances using optical fiber. The prototype antenna has been fully characterized to verify these design concepts.

  3. EFFECT OF ENLARGED FREE JET ON ENERGY CONVERSION IN PELTON TURBINE

    Institute of Scientific and Technical Information of China (English)

    LIU Jie; WEI Cai-xin; HAN Feng-qin

    2006-01-01

    In Pelton turbines, when the water jet emerges in the air, its velocity decreases downstream and its diameter increases to meet the continuity. In this paper, a physical parameter, the enlarging rate of jet diameter kDj was introduced and measured experimentally. The measurement of enlarging rate was carried out in three model turbines with different distributing Y-branch and nozzle configurations under various operating conditions. The effect of jet enlarging rate on the unsteady water sheet flow in the rotating buckets has not been investigated so far. This paper also presents the comparative numerical analysis of the flow in buckets at different enlarging rates of jet. It is shown that the effect of jet enlargement is so large that the flow pattern in the bucket is drastically changed by the latter half of the frames. The jet with large enlarging rate also introduces worse energy behavior to the hydraulic performance of the Pelton turbine. Besides, the phenomenon of jet interference was also discussed by using the results of numerical simulation for one jet. It indicates that the jet with large enlarging rate takes more risk that jet interference may damage the performance of multi-nozzle Pelton turbine.

  4. Loss of PTB or negative regulation of Notch mRNA reveals distinct zones of Notch and actin protein accumulation in Drosophila embryo.

    Directory of Open Access Journals (Sweden)

    Cedric S Wesley

    Full Text Available Polypyrimidine Tract Binding (PTB protein is a regulator of mRNA processing and translation. Genetic screens and studies of wing and bristle development during the post-embryonic stages of Drosophila suggest that it is a negative regulator of the Notch pathway. How PTB regulates the Notch pathway is unknown. Our studies of Drosophila embryogenesis indicate that (1 the Notch mRNA is a potential target of PTB, (2 PTB and Notch functions in the dorso-lateral regions of the Drosophila embryo are linked to actin regulation but not their functions in the ventral region, and (3 the actin-related Notch activity in the dorso-lateral regions might require a Notch activity at or near the cell surface that is different from the nuclear Notch activity involved in cell fate specification in the ventral region. These data raise the possibility that the Drosophila embryo is divided into zones of different PTB and Notch activities based on whether or not they are linked to actin regulation. They also provide clues to the almost forgotten role of Notch in cell adhesion and reveal a role for the Notch pathway in cell fusions.

  5. Evidence of non-canonical NOTCH signaling: Delta-like 1 homolog (DLK1) directly interacts with the NOTCH1 receptor in mammals.

    Science.gov (United States)

    Traustadóttir, Gunnhildur Ásta; Jensen, Charlotte H; Thomassen, Mads; Beck, Hans Christian; Mortensen, Sussi B; Laborda, Jorge; Baladrón, Victoriano; Sheikh, Søren P; Andersen, Ditte C

    2016-04-01

    Canonical NOTCH signaling, known to be essential for tissue development, requires the Delta-Serrate-LAG2 (DSL) domain for NOTCH to interact with its ligand. However, despite lacking DSL, Delta-like 1 homolog (DLK1), a protein that plays a significant role in mammalian development, has been suggested to interact with NOTCH1 and act as an antagonist. This non-canonical interaction is, however controversial, and evidence for a direct interaction, still lacking in mammals. In this study, we elucidated the putative DLK1-NOTCH1 interaction in a mammalian context. Taking a global approach and using Dlk1(+/+) and Dlk1(-/-) mouse tissues at E16.5, we demonstrated that several NOTCH signaling pathways indeed are affected by DLK1 during tissue development, and this was supported by a lower activation of NOTCH1 protein in Dlk1(+/+) embryos. Likewise, but using a distinct Dlk1-manipulated (siRNA) setup in a mammalian cell line, NOTCH signaling was substantially inhibited by DLK1. Using a mammalian two-hybrid system, we firmly established that the effect of DLK1 on NOTCH signaling was due to a direct interaction between DLK1 and NOTCH1. By careful dissection of this mechanism, we found this interaction to occur between EGF domains 5 and 6 of DLK1 and EGF domains 10-15 of NOTCH1. Thus, our data provide the first evidence for a direct interaction between DLK1 and NOTCH1 in mammals, and substantiate that non-canonical NOTCH ligands exist, adding to the complexity of NOTCH signaling.

  6. STABILITY AND MIXING CHARACTER FOR BUOYANT JETS IN QUIESCENT SHALLOW WATER

    Institute of Scientific and Technical Information of China (English)

    ZENG Yu-hong

    2005-01-01

    The near field stability and mixing characteristics of buoyant jets produced by thermal diffuse in quiescent shallow water are investigated numerically to predict under what combinations of discharge and ambient characteristics the near field will be stable or unstable.Analyses for different discharging types show that the discharge stability is purely dependent on the near-field behavior of the jets, or the dynamic interaction of the buoyant jet region, the surface impingement region and the internal hydraulic jump region, and is independent of the far-field geometry of the receiving water.The stability criterion is a function of the relative submerged depth, and source densimetric Froude number.

  7. Mapping the consequence of Notch1 proteolysis in vivo with NIP-CRE.

    NARCIS (Netherlands)

    Vooijs, M.; Ong, C.T.; Hadland, B.; Huppert, S.; Liu, Z.; Korving, J.; Born, M. van den; Stappenbeck, T.; Wu, Y.; Clevers, J.C.; Kopan, R.

    2007-01-01

    The four highly conserved Notch receptors receive short-range signals that control many biological processes during development and in adult vertebrate tissues. The involvement of Notch1 signaling in tissue self-renewal is less clear, however. We developed a novel genetic approach N(1)IP-CRE (Notch1

  8. Regulation of Notch signaling during T- and B-cell development by O-fucose glycans.

    Science.gov (United States)

    Stanley, Pamela; Guidos, Cynthia J

    2009-07-01

    Notch signaling is required for the development of all T cells and marginal zone (MZ) B cells. Specific roles in T- and B-cell differentiation have been identified for different Notch receptors, the canonical Delta-like (Dll) and Jagged (Jag) Notch ligands, and downstream effectors of Notch signaling. Notch receptors and ligands are post-translationally modified by the addition of glycans to extracellular domain epidermal growth factor-like (EGF) repeats. The O-fucose glycans of Notch cell-autonomously modulate Notch-ligand interactions and the strength of Notch signaling. These glycans are initiated by protein O-fucosyltransferase 1 (Pofut1), and elongated by the transfer of N-acetylglucosamine (GlcNAc) to the fucose by beta1,3GlcNAc-transferases termed lunatic, manic, or radical fringe. This review discusses T- and B-cell development from progenitors deficient in O-fucose glycans. The combined data show that Lfng and Mfng regulate T-cell development by enhancing the interactions of Notch1 in T-cell progenitors with Dll4 on thymic epithelial cells. In the spleen, Lfng and Mfng cooperate to modify Notch2 in MZ B progenitors, enhancing their interaction with Dll1 on endothelial cells and regulating MZ B-cell production. Removal of O-fucose affects Notch signaling in myelopoiesis and lymphopoiesis, and the O-fucose glycan in the Notch1 ligand-binding domain is required for optimal T-cell development.

  9. Genetic alteration in notch pathway is associated with better prognosis in renal cell carcinoma.

    Science.gov (United States)

    Feng, Chenchen; Xiong, Zuquan; Jiang, Haowen; Ding, Qiang; Fang, Zujun; Hui, Wen

    2016-01-01

    Notch signaling was associated with a variety of cancers but was not comprehensively studied in clear-cell renal cell carcinoma (ccRCC). We have in this study studied the genetic alteration (mutation and copy number variance) of Notch gene set in the Cancer Genome Atlas (TCGA) Kidney Renal Clear Cell Carcinoma (KIRC) database. We found that Notch pathway was frequently altered in ccRCC. The Notch gene set was genetically altered in 182 (44%) of the 415 ccRCC patients. CNV was the predominant type of alteration in most genes. Alterations in KAT2B and MAML1 occurred in 13% and 19% of patients, respectively, both of which were functionally active in ccRCC. Deletion of VHL was exclusively found in cases with Notch alteration. Overall survival was longer in ccRCC patients with altered-Notch pathway. The median survival was 90.41 months in Notch-altered cases and 69.15 in Notch-unaltered cases (P = 0.0404). The median disease free time was 89.82 months in Notch-altered cases and 77.27 months in in Notch-unaltered cases (P = 0.935). Conclusively, Notch signaling was altered in almost half of the ccRCC patients and copy number variances in MAML1 and KAT2B were predominant changes. These findings broadened our understanding of the role of Notch in ccRCC.

  10. Notch 1 as a potential therapeutic target in cutaneous T-cell lymphoma

    DEFF Research Database (Denmark)

    Kamstrup, Maria Rørbæk; Gjerdrum, Lise Mette Rahbek; Biskup, Edyta Urszula;

    2010-01-01

    mycosis fungoides (MyLa) and Sezary syndrome (SeAx, HuT-78)and in primary leukemic Sézary cells. Specific downregulation of Notch1 (but not Notch2 and Notch3) by siRNA induced apoptosis in SeAx. The mechanism of apoptosis involved the inhibition of NF-kappaB, which is the most important prosurvival...

  11. File list: Oth.ALL.20.Notch1.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.ALL.20.Notch1.AllCell mm9 TFs and others Notch1 All cell types SRX702806,SRX070...891,SRX070894,SRX702807,SRX516185,SRX114992,SRX884571,SRX884572 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.ALL.20.Notch1.AllCell.bed ...

  12. File list: Oth.Bld.50.Notch1.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.50.Notch1.AllCell mm9 TFs and others Notch1 Blood SRX070891,SRX070894,SRX70...2806,SRX702807,SRX516185,SRX114992,SRX884571,SRX884572 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.50.Notch1.AllCell.bed ...

  13. File list: Oth.ALL.05.Notch1.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.ALL.05.Notch1.AllCell mm9 TFs and others Notch1 All cell types SRX114992,SRX702...806,SRX702807,SRX070891,SRX070894,SRX516185,SRX884571,SRX884572 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.ALL.05.Notch1.AllCell.bed ...

  14. File list: Oth.Bld.20.Notch1.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.20.Notch1.AllCell mm9 TFs and others Notch1 Blood SRX702806,SRX070891,SRX07...0894,SRX702807,SRX516185,SRX114992,SRX884571,SRX884572 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.20.Notch1.AllCell.bed ...

  15. File list: Oth.Bld.10.Notch1.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.10.Notch1.AllCell mm9 TFs and others Notch1 Blood SRX114992,SRX702807,SRX70...2806,SRX070891,SRX070894,SRX516185,SRX884571,SRX884572 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.10.Notch1.AllCell.bed ...

  16. File list: Oth.ALL.10.Notch1.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.ALL.10.Notch1.AllCell mm9 TFs and others Notch1 All cell types SRX114992,SRX702...807,SRX702806,SRX070891,SRX070894,SRX516185,SRX884571,SRX884572 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.ALL.10.Notch1.AllCell.bed ...

  17. File list: Oth.Bld.05.Notch1.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.05.Notch1.AllCell mm9 TFs and others Notch1 Blood SRX114992,SRX702806,SRX70...2807,SRX070891,SRX070894,SRX516185,SRX884571,SRX884572 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.05.Notch1.AllCell.bed ...

  18. Influence of laser treatment on the fatigue of notched bar

    Institute of Scientific and Technical Information of China (English)

    ZhangHui; LingWeiye; JiangShouwei

    2003-01-01

    Fatigue cutting is a new approach for separating material. Man-made fatigue can be realized by applying a rotating bending load to a notched bar. To better utilize the new method, laser treatment is adopted in this study. After laser radiation at the notch root, the fatigue cycle of the bar drops dramatically. Based on the experimental result, we draw the conclusion that the fatigue of the bar is influenced by the shape of the hardened area. A hardened area that has a small axial dimension and a relatively large radial dimension facilitates the fatigue. The desirable hardened area can be obtained by controlling the laser treatment parameters.

  19. Immunohistochemical tools and techniques to visualize Notch in Drosophila melanogaster.

    Science.gov (United States)

    Tognon, Emiliana; Vaccari, Thomas

    2014-01-01

    The ability to accurately visualize proteins in Drosophila tissues is critical for studying their abundance and localization relative to the morphology of cells during tissue development and homeostasis. Here we describe the procedure to visualize Notch localization in whole-mount preparations of several Drosophila organs using confocal microscopy. The use of monoclonal antibodies directed to distinct portions of Notch allows one to follow the fate of the receptor during constitutive and inductive processes. The protocol described here can be used to co-label with antibodies recognizing markers of subcellular compartments in wild-type as well as mutant tissues.

  20. Use of notched beams to establish fracture criteria for beryllium

    Energy Technology Data Exchange (ETDEWEB)

    Mayville, R.A.

    1980-01-04

    The fracture of an improved form of pure beryllium was studied under triaxial tensile stresses. This state of stress was produced by testing notched beams, which were thick enough to be in a state of plane strain at the center. A plane strain, elastic-incremental plasticity finite element program was then used to determine the stress and strain distributions at fracture. A four-point bend fixture was used to load the specimens. It was carefully designed and manufactured to eliminate virtually all of the shear stresses at the reduced section of the notched beams. The unixial properties were obtained.

  1. 105 GHz Notch Filter Design for Collective Thomson Scattering

    DEFF Research Database (Denmark)

    Furtula, Vedran; Michelsen, Poul; Leipold, Frank;

    2011-01-01

    A millimeter-wave notch filter with 105-GHz center frequency, >20-GHz passband coverage, and 1-GHz rejection bandwidth has been constructed. The design is based on a fundamental rectangular waveguide with cylindrical cavities coupled by narrow iris gaps, i.e., small elongated holes of negligible...... thickness. We use numerical simulations to study the sensitivity of the notch filter performance to changes in geometry and in material conductivity within a bandwidth of ±10 GHz. The constructed filter is tested successfully using a vector network analyzer monitoring a total bandwidth of 20 GHz...

  2. Mechano sorptive behaviour of notched beams in bending

    DEFF Research Database (Denmark)

    Jensen, Signe Kamp; Hoffmeyer, Preben

    1996-01-01

    Short term bending tests with end-notched beams at constant or varying moisture content have shown an apparent contradictory dependency between moisture content and strength. The higher the moisture content the higher the strength. Varying moisture results in particularly significant differences...... and by neglecting deformation due to shear. Compression stresses perpendicular to grain in excess of 6 MPa were found in the vicinity of the notch following a period of adsorption. Similarly, small tension stresses of the order 1 MPa were registered in this area when the specimens were at their most dry condition...

  3. Notch sensitivity of hydrogenated oxygen-strengthened titanium

    Science.gov (United States)

    Wasz, M. L.; Ko, C. C.; Brotzen, F. R.; Mclellan, R. B.

    1990-01-01

    While earlier studies have shown that the tensile properties and fracture test intensity factors of oxygen-strengthened Ti remain nearly unaffected by the presence of about 70 ppm (weight) hydrogen, the Charpy V-notch test-determined impact properties of oxygen-bearing Ti are strongly affected by the presence of hydrogen. The present study establishes that, concurrently with the strengthening effect of oxygen, there is a substantial lowering of ductility. The presence of hydrogen has virtually no effect on the notch strength of Ti alloys of either low or high oxygen content, where hydrogen contents lie in the 25-80 range.

  4. Faraday, Jets, and Sand

    NARCIS (Netherlands)

    Sandtke, M.; van der Meer, Roger M.; Versluis, Andreas Michel; Lohse, Detlef

    2003-01-01

    When a 6-mm layer of fine sand with an average grain size of 40 µm is poured into a cylindrical container and shaken vertically, thin jets are seen to emerge from an airy cloud of grains, almost like protuberances from the corona of the sun. A quasi two-dimensional setup reveals the jet-formation

  5. Numerical Prediction of Differences in Micromechanical Fracture Sequence in Notched and Un-Notched Wires for Civil Engineering Applications

    Directory of Open Access Journals (Sweden)

    Adewole, K.K.

    2014-01-01

    Full Text Available The need to employ simulation-based investigations of fracture of civil engineering structures has been emphasised recently in literature. In this paper, three dimensional finite element simulations revealed that the cup and cone fracture process in channel-shaped notched wire for civil engineering applications begins with a slant fracture at the root of the outer edge of the channel-shaped notch and follows a slant to flat fracture sequence. These results demonstrate that the fracture origin in cup and cone fracture in notched wires for civil engineering applications does not necessarily begin with a flat fracture at the center of the wire and does not necessarily follows the flat to slant fracture sequence or propagation generally reported in literature. These results further demonstrate the need to employ simulation-based methodologies in conjunction with or as an alternative to purely experimental fractographic analysis for an accurate failure analysis of wires used for civil engineering applications.

  6. Jet propulsion without inertia

    CERN Document Server

    Spagnolie, Saverio E

    2010-01-01

    A body immersed in a highly viscous fluid can locomote by drawing in and expelling fluid through pores at its surface. We consider this mechanism of jet propulsion without inertia in the case of spheroidal bodies, and derive both the swimming velocity and the hydrodynamic efficiency. Elementary examples are presented, and exact axisymmetric solutions for spherical, prolate spheroidal, and oblate spheroidal body shapes are provided. In each case, entirely and partially porous (i.e. jetting) surfaces are considered, and the optimal jetting flow profiles at the surface for maximizing the hydrodynamic efficiency are determined computationally. The maximal efficiency which may be achieved by a sphere using such jet propulsion is 12.5%, a significant improvement upon traditional flagella-based means of locomotion at zero Reynolds number. Unlike other swimming mechanisms which rely on the presentation of a small cross section in the direction of motion, the efficiency of a jetting body at low Reynolds number increas...

  7. Impact of Spectral Notch Width on Neurophysiological Plasticity and Clinical Effectiveness of the Tailor-Made Notched Music Training.

    Directory of Open Access Journals (Sweden)

    Robert Wunderlich

    Full Text Available Tinnitus, the ringing in the ears that is unrelated to any external source, causes a significant loss in quality of life, involving sleep disturbance and depression for 1 to 3% of the general population. While in the first place tinnitus may be triggered by damage to the inner ear cells, the neural generators of subjective tinnitus are located in central regions of the nervous system. A loss of lateral inhibition, tonotopical reorganization and a gain-increase in response to the sensory deprivation result in hypersensitivity and hyperactivity in certain regions of the auditory cortex. In the tailor-made notched music training (TMNMT patients listen to music from which the frequency spectrum of the tinnitus has been removed. This evokes strong lateral inhibition from neurons tuned to adjacent frequencies onto the neurons involved in the tinnitus percept. A reduction of tinnitus loudness and tinnitus-related neural activity was achieved with TMNMT in previous studies. As the effect of lateral inhibition depends on the bandwidth of the notch, in the current study we altered the notch width to find the most effective notch width for TMNMT. We compared 1-octave notch width with ½-octave and ¼-octave. Participants chose their favorite music for the training that included three month of two hours daily listening. The outcome was measured by means of standardized questionnaires and magnetoencephalography. We found a general reduction of tinnitus distress in all administered tinnitus questionnaires after the training. Additionally, tinnitus-related neural activity was reduced after the training. Nevertheless, notch width did not have an influence on the behavioral or neural effects of TMNMT. This could be due to a non-linear resolution of lateral inhibition in high frequencies.

  8. Impact of Spectral Notch Width on Neurophysiological Plasticity and Clinical Effectiveness of the Tailor-Made Notched Music Training.

    Science.gov (United States)

    Wunderlich, Robert; Lau, Pia; Stein, Alwina; Engell, Alva; Wollbrink, Andreas; Rudack, Claudia; Pantev, Christo

    2015-01-01

    Tinnitus, the ringing in the ears that is unrelated to any external source, causes a significant loss in quality of life, involving sleep disturbance and depression for 1 to 3% of the general population. While in the first place tinnitus may be triggered by damage to the inner ear cells, the neural generators of subjective tinnitus are located in central regions of the nervous system. A loss of lateral inhibition, tonotopical reorganization and a gain-increase in response to the sensory deprivation result in hypersensitivity and hyperactivity in certain regions of the auditory cortex. In the tailor-made notched music training (TMNMT) patients listen to music from which the frequency spectrum of the tinnitus has been removed. This evokes strong lateral inhibition from neurons tuned to adjacent frequencies onto the neurons involved in the tinnitus percept. A reduction of tinnitus loudness and tinnitus-related neural activity was achieved with TMNMT in previous studies. As the effect of lateral inhibition depends on the bandwidth of the notch, in the current study we altered the notch width to find the most effective notch width for TMNMT. We compared 1-octave notch width with ½-octave and ¼-octave. Participants chose their favorite music for the training that included three month of two hours daily listening. The outcome was measured by means of standardized questionnaires and magnetoencephalography. We found a general reduction of tinnitus distress in all administered tinnitus questionnaires after the training. Additionally, tinnitus-related neural activity was reduced after the training. Nevertheless, notch width did not have an influence on the behavioral or neural effects of TMNMT. This could be due to a non-linear resolution of lateral inhibition in high frequencies.

  9. Notch activation by phenethyl isothiocyanate attenuates its inhibitory effect on prostate cancer cell migration.

    Directory of Open Access Journals (Sweden)

    Su-Hyeong Kim

    Full Text Available Phenethyl isothiocyanate (PEITC is a promising cancer chemopreventive component of edible cruciferous vegetables with in vivo efficacy against prostate cancer in experimental rodents. Cancer chemopreventive response to PEITC is characterized by its ability to inhibit multiple oncogenic signaling pathways, including nuclear factor-κB, Akt, and androgen receptor. The present study demonstrates, for the first time, that PEITC treatment activates Notch signaling in malignant as well as normal human prostate cells. Exposure of human prostate cancer cells (LNCaP, PC-3, and DU145 and a normal human prostate epithelial cell line (PrEC to PEITC resulted in cleavage (active form of Notch1 and Notch2, and increased transcriptional activity of Notch. In PC-3 and LNCaP cells, PEITC treatment caused induction of Notch ligands Jagged1 and Jagged2 (PC-3, overexpression of γ-secretase complex components Presenilin1 and Nicastrin (PC-3, nuclear enrichment of cleaved Notch2, and/or up-regulation of Notch1, Notch2, Jagged1, and/or Jagged2 mRNA. PEITC-induced apoptosis in LNCaP and PC-3 cells was significantly attenuated by RNA interference of Notch2, but not by pharmacological inhibition of Notch1. Inhibition of PC-3 and LNCaP cell migration resulting from PEITC exposure was significantly augmented by knockdown of Notch2 protein as well as pharmacological inhibition of Notch1 activation. Nuclear expression of cleaved Notch2 protein was significantly higher in PC-3 xenografts from PEITC-treated mice and dorsolateral prostates from PEITC-fed TRAMP mice compared with respective control. Because Notch signaling is implicated in epithelial-mesenchymal transition and metastasis, the present study suggests that anti-metastatic effect of PEITC may be augmented by a combination regimen involving a Notch inhibitor.

  10. TSG attenuates LPC-induced endothelial cells inflammatory damage through notch signaling inhibition.

    Science.gov (United States)

    Zhao, Jing; Liang, Yuan; Song, Fan; Xu, Shouzhu; Nian, Lun; Zhou, Xuanxuan; Wang, Siwang

    2016-01-01

    Lysophosphatidylcholine (LPC) induces inflammation in endothelial cells (ECs) but the mechanism is not fully understood. The Notch signaling pathway is involved in chronic EC inflammation, but its functions in LPC-induced endothelial inflammatory damage and 2,3,5,4'-tetrahydroxystilbene-2-O-β-d-glucoside's (TSG) protective effect during LPC-induced inflammatory damage in human umbilical vein endothelial cells (HUVECs) is largely unknown. We report that Notch signaling activation contributed to LPC-induced injury in HUVECs, and that TSG protected HUVECs from LPC-induced injury by antagonizing Notch signaling activation by LPC. γ-secretase inhibitor (DAPT), a specific inhibitor of the Notch signaling pathway, and Notch1 siRNA were used to inhibit Notch activity. HUVECs were exposed to LPC in the presence or absence of TSG, DAPT, and Notch1 siRNA. LPC treatment of HUVECs resulted in reduced cell viability, and Notch1 and Hes1 upregulation. Either silencing of Notch1 by siRNA or pharmacological inhibition of Notch signaling by DAPT prevented the loss of cell viability, and induction of apoptosis, and enhanced expression Notch1, Hes1 and MCP-1 by LPC in HUVECs. Similarly, TSG reduced LPC stimulation of Notch1, Hes1, and MCP-1 expression, prevented the release of IL-6 and CRP and rescued HUVECs from LPC-induced cell damage. Our data indicate that the Notch signaling pathway is a crucial mediator of endothelial inflammatory damage and that TSG protects against endothelial inflammatory damage by inhibiting the Notch signaling pathway. Our findings suggest that targeting Notch signaling by natural products such as TSG is a promising strategy for the prevention and treatment of chronic inflammation associated diseases, including atherosclerosis. © 2015 IUBMB Life, 68(1):37-50, 2016.

  11. Complex Fluids and Hydraulic Fracturing.

    Science.gov (United States)

    Barbati, Alexander C; Desroches, Jean; Robisson, Agathe; McKinley, Gareth H

    2016-06-07

    Nearly 70 years old, hydraulic fracturing is a core technique for stimulating hydrocarbon production in a majority of oil and gas reservoirs. Complex fluids are implemented in nearly every step of the fracturing process, most significantly to generate and sustain fractures and transport and distribute proppant particles during and following fluid injection. An extremely wide range of complex fluids are used: naturally occurring polysaccharide and synthetic polymer solutions, aqueous physical and chemical gels, organic gels, micellar surfactant solutions, emulsions, and foams. These fluids are loaded over a wide range of concentrations with particles of varying sizes and aspect ratios and are subjected to extreme mechanical and environmental conditions. We describe the settings of hydraulic fracturing (framed by geology), fracturing mechanics and physics, and the critical role that non-Newtonian fluid dynamics and complex fluids play in the hydraulic fracturing process.

  12. Hydraulic properties of ladle slags

    Directory of Open Access Journals (Sweden)

    J. Vlček

    2016-07-01

    Full Text Available The article presents results of examining of hydraulic properties of ladle slags formed during production of steel. The studied ladle slags were subjected to different cooling mode from the molten state. Based on the ability of the slag react with the water was assessed their hydraulic activity. The hydraulic properties are caused by the presence of minerals dicalcium silicate, tricalcium aluminate, mayenite, brownmillerite and dicalcium ferite. The emergence of required hydrating phases in the ladle slags is conditioned by a sufficient CaO content and their cooling rate. The contact the slag with water during processing and their ageing has a negative effect. The experiment has shown that the phase transformation of the mineral dicalcium silicate which occurs during cooling of the ladle slags cause their volume instability.

  13. Simulations of Solar Jets

    Science.gov (United States)

    Kohler, Susanna

    2017-02-01

    Formation of a coronal jet from twisted field lines that have reconnected with the ambient field. The colors show the radial velocity of the plasma. [Adapted from Szente et al. 2017]How do jets emitted from the Suns surface contribute to its corona and to the solar wind? In a recent study, a team of scientists performed complex three-dimensional simulations of coronal jets to answer these questions.Small ExplosionsCoronal jets are relatively small eruptions from the Suns surface, with heights of roughly 100 to 10,000 km, speeds of 10 to 1,000 km/s, and lifetimes of a few minutes to around ten hours. These jets are constantly present theyre emitted even from the quiet Sun, when activity is otherwise low and weve observed them with a fleet of Sun-watching space telescopes spanning the visible, extreme ultraviolet (EUV), and X-ray wavelength bands.A comparison of simulated observations based on the authors model (left panels) to actual EUV and X-ray observations of jets (right panels). [Szente et al. 2017]Due to their ubiquity, we speculate that these jets might contribute to heating the global solar corona (which is significantly hotter than the surface below it, a curiosity known as the coronal heating problem). We can also wonder what role these jets might play in driving the overall solar wind.Launching a JetLed by Judit Szente (University of Michigan), a team of scientists has explored the impact of coronal jets on the global corona and solar wind with a series of numerical simulations. Szente and collaborators used three-dimensional, magnetohydrodynamic simulations that provide realistic treatment of the solar atmosphere, the solar wind acceleration, and the complexities of heat transfer throughout the corona.In the authors simulations, a jet is initiated as a magnetic dipole rotates at the solar surface, winding up field lines. Magnetic reconnection between the twisted lines and the background field then launches the jet from the dense and hot solar

  14. Effect of Notch Location on Fatigue Life Prediction of Strength Mismatched HSLA Steel Weldments

    Institute of Scientific and Technical Information of China (English)

    S. Ravi; V. Balasubramanian; S. Nemat Nasser

    2004-01-01

    Welding of high strength low alloy steels (HSLA) involves usage of Iow, even and high strength filler materials (electrodes) than the parent material depending on the application of the welded structures and the availability of the filler material. In the present investigation, the fatigue crack growth behaviour of weld metal (WM) and heat affected zone (HAZ) regions of under matched (UM), equal matched (EM) and over matched (OM)joints has been studied. The base material used in this investigation is HSLA-80 steel of weldable grade. Shielded metal arc welding (SMAW) process has been used to fabricate the butt joints. Centre cracked tension (CCT) specimen has been used to evaluate the fatigue crack growth behaviour of the welded joints. Fatigue crack growth experiments have been conducted using servo hydraulic controlled fatigue testing machine at constant amplitude loading (R=0). A method has been proposed to predict the fatigue life of HSLA steel welds using fracture mechanics approach by incorporating influences of mismatch ratio (MMR) and notch location.

  15. Hydraulic resistance of biofilms

    KAUST Repository

    Dreszer, C.

    2013-02-01

    Biofilms may interfere with membrane performance in at least three ways: (i) increase of the transmembrane pressure drop, (ii) increase of feed channel (feed-concentrate) pressure drop, and (iii) increase of transmembrane passage. Given the relevance of biofouling, it is surprising how few data exist about the hydraulic resistance of biofilms that may affect the transmembrane pressure drop and membrane passage. In this study, biofilms were generated in a lab scale cross flow microfiltration system at two fluxes (20 and 100Lm-2h-1) and constant cross flow (0.1ms-1). As a nutrient source, acetate was added (1.0mgL-1 acetate C) besides a control without nutrient supply. A microfiltration (MF) membrane was chosen because the MF membrane resistance is very low compared to the expected biofilm resistance and, thus, biofilm resistance can be determined accurately. Transmembrane pressure drop was monitored. As biofilm parameters, thickness, total cell number, TOC, and extracellular polymeric substances (EPS) were determined, it was demonstrated that no internal membrane fouling occurred and that the fouling layer actually consisted of a grown biofilm and was not a filter cake of accumulated bacterial cells. At 20Lm-2h-1 flux with a nutrient dosage of 1mgL-1 acetate C, the resistance after 4 days reached a value of 6×1012m-1. At 100Lm-2h-1 flux under the same conditions, the resistance was 5×1013m-1. No correlation of biofilm resistance to biofilm thickness was found; Biofilms with similar thickness could have different resistance depending on the applied flux. The cell number in biofilms was between 4×107 and 5×108 cellscm-2. At this number, bacterial cells make up less than a half percent of the overall biofilm volume and therefore did not hamper the water flow through the biofilm significantly. A flux of 100Lm-2h-1 with nutrient supply caused higher cell numbers, more biomass, and higher biofilm resistance than a flux of 20Lm-2h-1. However, the biofilm thickness

  16. Structural basis for cooperativity in recruitment of MAML coactivators to Notch transcription complexes.

    Science.gov (United States)

    Nam, Yunsun; Sliz, Piotr; Song, Luyan; Aster, Jon C; Blacklow, Stephen C

    2006-03-10

    Notch receptors transduce essential developmental signals between neighboring cells by forming a complex that leads to transcription of target genes upon activation. We report here the crystal structure of a Notch transcriptional activation complex containing the ankyrin domain of human Notch1 (ANK), the transcription factor CSL on cognate DNA, and a polypeptide from the coactivator Mastermind-like-1 (MAML-1). Together, CSL and ANK create a groove to bind the MAML-1 polypeptide as a kinked, 70 A helix. The composite binding surface likely restricts the recruitment of MAML proteins to promoters on which Notch:CSL complexes have been preassembled, ensuring tight transcriptional control of Notch target genes.

  17. The Variability of Fatigue in Notched Bars of IN100 (Preprint)

    Science.gov (United States)

    2012-08-01

    conducted having nominally 40 m micro-notches machined using focused ion beam ( FIB ) in the geometric center of the two notches. These micro-notches... FIB crack starters in the notch and replicated to measure the small crack growth rates. This also allows a comparison of the small crack growth...ID JAI19045. 8) M. Aratani and J.F. Knott , “The Growth of Short Fatigue Cracks Ahead of a Notch in High Strength Steel,” Eng. Failure. Anal., 17

  18. On the Notch Effect in Low Temperature Carburized Stainless Steel under Fatigue

    Directory of Open Access Journals (Sweden)

    Minak G.

    2010-06-01

    Full Text Available The present paper describes the fatigue behaviour of carburized notched AISI 316 austenitic stainless steel specimens. Rotary four point bending fatigue tests have been performed using carburized smooth specimens with two different values of surface rugosity and notched specimen with two different stress concentration factors Kt, of 3.55 and 6.50 and the effects of carburizing on fatigue strength and notch sensitivity were discussed. Results show a general improvement of the fatigue life due to the treatment for all the series with an apparent notch sensitivity lower than one in the case of blunt notches due to secondary effects that were singled out.

  19. On the Notch Effect in Low Temperature Carburized Stainless Steel under Fatigue

    Science.gov (United States)

    Minak, G.

    2010-06-01

    The present paper describes the fatigue behaviour of carburized notched AISI 316 austenitic stainless steel specimens. Rotary four point bending fatigue tests have been performed using carburized smooth specimens with two different values of surface rugosity and notched specimen with two different stress concentration factors Kt, of 3.55 and 6.50 and the effects of carburizing on fatigue strength and notch sensitivity were discussed. Results show a general improvement of the fatigue life due to the treatment for all the series with an apparent notch sensitivity lower than one in the case of blunt notches due to secondary effects that were singled out.

  20. Controls of Hydraulic Wind Turbine

    Directory of Open Access Journals (Sweden)

    Zhang Yin

    2016-01-01

    Full Text Available In this paper a hydraulic wind turbine generator system was proposed based on analysis the current wind turbines technologies. The construction and principles were introduced. The mathematical model was verified using MATLAB and AMsim. A displacement closed loop of swash plate of motor and a speed closed loop of generator were setup, a PID control is introduced to maintain a constant speed and fixed frequency at wind turbine generator. Simulation and experiment demonstrated that the system can connect grid to generate electric and enhance reliability. The control system demonstrates a high performance speed regulation and effectiveness. The results are great significant to design a new type hydraulic wind turbine system.

  1. Notch reporter activity in breast cancer cell lines identifies a subset of cells with stem cell activity.

    Science.gov (United States)

    D'Angelo, Rosemarie C; Ouzounova, Maria; Davis, April; Choi, Daejin; Tchuenkam, Stevie M; Kim, Gwangil; Luther, Tahra; Quraishi, Ahmed A; Senbabaoglu, Yasin; Conley, Sarah J; Clouthier, Shawn G; Hassan, Khaled A; Wicha, Max S; Korkaya, Hasan

    2015-03-01

    Developmental pathways such as Notch play a pivotal role in tissue-specific stem cell self-renewal as well as in tumor development. However, the role of Notch signaling in breast cancer stem cells (CSC) remains to be determined. We utilized a lentiviral Notch reporter system to identify a subset of cells with a higher Notch activity (Notch(+)) or reduced activity (Notch(-)) in multiple breast cancer cell lines. Using in vitro and mouse xenotransplantation assays, we investigated the role of the Notch pathway in breast CSC regulation. Breast cancer cells with increased Notch activity displayed increased sphere formation as well as expression of breast CSC markers. Interestingly Notch(+) cells displayed higher Notch4 expression in both basal and luminal breast cancer cell lines. Moreover, Notch(+) cells demonstrated tumor initiation capacity at serial dilutions in mouse xenografts, whereas Notch(-) cells failed to generate tumors. γ-Secretase inhibitor (GSI), a Notch blocker but not a chemotherapeutic agent, effectively targets these Notch(+) cells in vitro and in mouse xenografts. Furthermore, elevated Notch4 and Hey1 expression in primary patient samples correlated with poor patient survival. Our study revealed a molecular mechanism for the role of Notch-mediated regulation of breast CSCs and provided a compelling rationale for CSC-targeted therapeutics.

  2. Impact of hydraulic well restoration on native bacterial communities in drinking water wells.

    Science.gov (United States)

    Karwautz, Clemens; Lueders, Tillmann

    2014-01-01

    The microbial monitoring of drinking water production systems is essential to assure water quality and minimize possible risks. However, the comparative impact of microbes from the surrounding aquifer and of those established within drinking water wells on water parameters remains poorly understood. High pressure jetting is a routine method to impede well clogging by fine sediments and also biofilms. In the present study, bacterial communities were investigated in a drinking water production system before, during, and after hydraulic purging. Variations were observed in bacterial communities between different wells of the same production system before maintenance, despite them having practically identical water chemistries. This may have reflected the distinct usage practices of the different wells, and also local aquifer heterogeneity. Hydraulic jetting of one well preferentially purged a subset of the dominating taxa, including lineages related to Diaphorobacter, Nitrospira, Sphingobium, Ralstonia, Alkanindiges, Janthinobacterium, and Pseudomonas spp, suggesting their tendency for growth in well-associated biofilms. Lineages of potential drinking water concern (i.e. Legionellaceae, Pseudomonadaceae, and Acinetobacter spp.) reacted distinctly to hydraulic jetting. Bacterial diversity was markedly reduced in drinking water 2 weeks after the cleaning procedure. The results of the present study provide a better understanding of drinking water wells as a microbial habitat, as well as their role in the microbiology of drinking water systems.

  3. Integrating hydraulic equivalent sections into a hydraulic geometry study

    Science.gov (United States)

    Jia, Yanhong; Yi, Yujun; Li, Zhiwei; Wang, Zhaoyin; Zheng, Xiangmin

    2017-09-01

    Hydraulic geometry (HG) is an important geomorphic concept that has played an indispensable role in hydrological analyses, physical studies of streams, ecosystem and aquatic habitat studies, and sedimentology research. More than 60 years after Leopold and Maddock (1953) first introduced the concept of HG, researchers have still not uncovered the physical principles underlying HG behavior. One impediment is the complexity of the natural river cross section. The current study presents a new way to simplify the cross section, namely, the hydraulic equivalent section, which is generalized from the cross section in the ;gradually varied flow of an alluvial river; (GVFAR) and features hydrodynamic properties and bed-building laws similar to those of the GVFAR. Energy balance was used to derive the stage Z-discharge Q relationship in the GVFAR. The GVFAR in the Songhua River and the Yangtze River were selected as examples. The data, including measured discharge, river width, water stage, water depth, wet area, and cross section, were collected from the hydrological yearbooks of typical hydrological stations on the Songhua River and the Yangtze River from 1955 to 1987. The relationships between stage Z-discharge Q and cross-sectional area A-stage Z at various stations were analyzed, and ;at-a-station hydraulic geometry; (AHG) relationships were obtained in power-law forms. Based on derived results and observational data analysis, the Z-Q and Z-A relationships of AHG were similar to rectangular weir flows, thus the cross section of the GVFAR was generalized as a compound rectangular, hydraulic equivalent cross section. As to bed-building characteristics, the bankfull discharge method and the stage-discharge-relation method were used to calculate the dominant variables of the alluvial river. This hydraulic equivalent section has the same Z-Q relation, Z-A relation, dominant discharge, dominant river width, and dominant water depth as the cross section in the GVFAR. With the

  4. Jets and QCD

    Energy Technology Data Exchange (ETDEWEB)

    Ali, A. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Kramer, G. [Hamburg Univ. (Germany). II. Inst. fuer Theoretische Physik

    2010-12-15

    The observation of quark and gluon jets has played a crucial role in establishing Quantum Chromodynamics [QCD] as the theory of the strong interactions within the Standard Model of particle physics. The jets, narrowly collimated bundles of hadrons, reflect configurations of quarks and gluons at short distances. Thus, by analysing energy and angular distributions of the jets experimentally, the properties of the basic constituents of matter and the strong forces acting between them can be explored. In this review we summarise the properties of quark and gluon jets and the impact of their observation on Quantum Chromodynamics, primarily the discovery of the gluons as the carriers of the strong force. Focusing on these basic points, jets in e{sup +}e{sup -} collisions will be in the foreground of the discussion. In addition we will delineate the role of jets as tools for exploring other particle aspects in ep and pp/p anti p collisions - quark and gluon densities in protons, measurements of the QCD coupling, fundamental 2-2 quark/gluon scattering processes, but also the impact of jet decays of top quarks, and W{sup {+-}},Z bosons on the electroweak sector. The presentation to a large extent is formulated in a non-technical language with the intent to recall the significant steps historically and convey the significance of this field also to communities beyond high energy physics. (orig.)

  5. Solar coronal jets

    Science.gov (United States)

    Dobrzyck, D.

    The solar jets were first observed by SOHO instruments (EIT, LASCO, UVCS) during the previous solar minimum. They were small, fast ejections originating from flaring UV bright points within large polar coronal holes. The obtained data provided us with estimates of the jet plasma conditions, dynamics, evolution of the electron temperature and heating rate required to reproduce the observed ionization state. To follow the polar jets through the solar cycle a special SOHO Joint Observing Program (JOP 155) was designed. It involves a number of SOHO instruments (EIT, CDS, UVCS, LASCO) as well as TRACE. The coordinated observations have been carried out since April 2002. The data enabled to identify counterparts of the 1996-1998 solar minimum jets. Their frequency of several events per day appear comparable to the frequency from the previous solar minimum. The jets are believed to be triggered by field line reconnection between emerging magnetic dipole and pre-existing unipolar field. Existing models predict that the hot jet is formed together with another jet of a cool material. The particular goal of the coordinated SOHO and TRACE observations was to look for possible association of the hot and cool plasma ejections. Currently there is observational evidence that supports these models.

  6. Assembly of a Notch transcriptional activation complex requires multimerization.

    Science.gov (United States)

    Vasquez-Del Carpio, Rodrigo; Kaplan, Fred M; Weaver, Kelly L; VanWye, Jeffrey D; Alves-Guerra, Marie-Clotilde; Robbins, David J; Capobianco, Anthony J

    2011-04-01

    Notch transmembrane receptors direct essential cellular processes, such as proliferation and differentiation, through direct cell-to-cell interactions. Inappropriate release of the intracellular domain of Notch (N(ICD)) from the plasma membrane results in the accumulation of deregulated nuclear N(ICD) that has been linked to human cancers, notably T-cell acute lymphoblastic leukemia (T-ALL). Nuclear N(ICD) forms a transcriptional activation complex by interacting with the coactivator protein Mastermind-like 1 and the DNA binding protein CSL (for CBF-1/Suppressor of Hairless/Lag-1) to regulate target gene expression. Although it is well understood that N(ICD) forms a transcriptional activation complex, little is known about how the complex is assembled. In this study, we demonstrate that N(ICD) multimerizes and that these multimers function as precursors for the stepwise assembly of the Notch activation complex. Importantly, we demonstrate that the assembly is mediated by N(ICD) multimers interacting with Skip and Mastermind. These interactions form a preactivation complex that is then resolved by CSL to form the Notch transcriptional activation complex on DNA.

  7. Failure of a porous solid from a deep notch

    DEFF Research Database (Denmark)

    Redanz, Pia; Fleck, Norman A.; McMeeking, Robert M.

    1997-01-01

    -size dependent thereafter. The initiation of crack growth at the notch root is assumed to occur when a critical level of porosity is attained. The results show that the shape of the plastic zone for both the Gurson and the FKM material is highly dependent on the initial porosity. In the case of low initial...

  8. Mechano sorptive behaviour of notched beams in bending

    DEFF Research Database (Denmark)

    Jensen, Signe Kamp; Hoffmeyer, Preben

    1996-01-01

    and by neglecting deformation due to shear. Compression stresses perpendicular to grain in excess of 6 MPa were found in the vicinity of the notch following a period of adsorption. Similarly, small tension stresses of the order 1 MPa were registered in this area when the specimens were at their most dry condition...

  9. DLK1 and the Notch pathway in the liver

    NARCIS (Netherlands)

    Falix, F.A.

    2012-01-01

    Het is onduidelijk waarom bij sommige kinderen een kwaadaardige vorm van leverkanker ontstaat. Farah Falix onderzocht de rol van twee eiwitten, DLK1 en Notch2, tijdens de leverontwikkeling. Het DLK1-eiwit is normaal alleen aanwezig in de embryonale lever. Het verschijnt ook bij een hepatoblastoom (k

  10. Notch inhibits Yorkie activity in Drosophila wing discs.

    Directory of Open Access Journals (Sweden)

    Alexandre Djiane

    Full Text Available During development, tissues and organs must coordinate growth and patterning so they reach the right size and shape. During larval stages, a dramatic increase in size and cell number of Drosophila wing imaginal discs is controlled by the action of several signaling pathways. Complex cross-talk between these pathways also pattern these discs to specify different regions with different fates and growth potentials. We show that the Notch signaling pathway is both required and sufficient to inhibit the activity of Yorkie (Yki, the Salvador/Warts/Hippo (SWH pathway terminal transcription activator, but only in the central regions of the wing disc, where the TEAD factor and Yki partner Scalloped (Sd is expressed. We show that this cross-talk between the Notch and SWH pathways is mediated, at least in part, by the Notch target and Sd partner Vestigial (Vg. We propose that, by altering the ratios between Yki, Sd and Vg, Notch pathway activation restricts the effects of Yki mediated transcription, therefore contributing to define a zone of low proliferation in the central wing discs.

  11. An evaluation of Top Notch fundamental A and B

    Directory of Open Access Journals (Sweden)

    Mahboobeh Tavakol

    2013-11-01

    Full Text Available Adopting the appropriate textbook is a controversial task for second/foreign language teachers. In Iranian EFL situation where the teachers are not usually textbook providers but just consumers of other peoples material, there might be a need to evaluate the available EFL textbooks and investigate their contribution to general English courses. This paper aims at evaluating Top Notch fundamentals in terms of their impact on Iranian learners’ communicative and pragmatic competence. It is based on a comparison between Top Notch and Introductory Interchange (third edition (Intro Interchange afterwards to evaluate the extent of their applicability for schools and institutes communicative EFL courses. A checklist consisting of 38 items is also provided and distributed among seven raters who had the experience of teaching Top Notch Fundamentals and Intro Interchange. The results of the completed checklists are added to the related sections. This step by step comparison has revealed that both textbooks are almost the same in most parts. In fact, it must be notified that while they are appropriate to be applied for communicative English courses and provide the learners with enough authentic input and opportunity to promote four major skills, they suffer from several drawbacks. Finally it is concluded that Top Notch is only appropriate to be practiced in general English courses in foreign language institutes; however, Interchange as a dominating EFL textbook regardless of all its deficiencies, is flexible enough to be used, as it has been successfully for years, in both foreign language institutes and schools in Iran.

  12. Regularized Adaptive Notch Filters for Acoustic Howling Suppression

    DEFF Research Database (Denmark)

    Gil-Cacho, Pepe; van Waterschoot, Toon; Moonen, Marc;

    2009-01-01

    In this paper, a method for the suppression of acoustic howling is developed, based on adaptive notch filters (ANF) with regularization (RANF). The method features three RANFs working in parallel to achieve frequency tracking, howling detection and suppression. The ANF-based approach to howling...

  13. Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xin-Hua [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Yao, Shen; Qiao, Rui-Fang; Levine, Alice C. [Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Kirschenbaum, Alexander [Department of Urology, Mount Sinai School of Medicine, New York, NY 10029 (United States); Pan, Jiangping; Wu, Yong [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Qin, Weiping [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Bauman, William A. [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Cardozo, Christopher P., E-mail: chris.cardozo@mssm.edu [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States)

    2011-10-14

    Highlights: {yields} Nerve transection increased Notch signaling in paralyzed muscle. {yields} Nandrolone prevented denervation-induced Notch signaling. {yields} Nandrolone induced the expression of an inhibitor of the Notch signaling, Numb. {yields} Reduction of denervation-induced Notch signaling by nandrolone is likely through upregulation of Numb. -- Abstract: Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy.

  14. Jagged1 is the pathological link between Wnt and Notch pathways in colorectal cancer.

    Science.gov (United States)

    Rodilla, Verónica; Villanueva, Alberto; Obrador-Hevia, Antonia; Robert-Moreno, Alex; Fernández-Majada, Vanessa; Grilli, Andrea; López-Bigas, Nuria; Bellora, Nicolás; Albà, M Mar; Torres, Ferran; Duñach, Mireia; Sanjuan, Xavier; Gonzalez, Sara; Gridley, Thomas; Capella, Gabriel; Bigas, Anna; Espinosa, Lluís

    2009-04-14

    Notch has been linked to beta-catenin-dependent tumorigenesis; however, the mechanisms leading to Notch activation and the contribution of the Notch pathway to colorectal cancer is not yet understood. By microarray analysis, we have identified a group of genes downstream of Wnt/beta-catenin (down-regulated when blocking Wnt/beta-catenin) that are directly regulated by Notch (repressed by gamma-secretase inhibitors and up-regulated by active Notch1 in the absence of beta-catenin signaling). We demonstrate that Notch is downstream of Wnt in colorectal cancer cells through beta-catenin-mediated transcriptional activation of the Notch-ligand Jagged1. Consistently, expression of activated Notch1 partially reverts the effects of blocking Wnt/beta-catenin pathway in tumors implanted s.c. in nude mice. Crossing APC(Min/+) with Jagged1(+/Delta) mice is sufficient to significantly reduce the size of the polyps arising in the APC mutant background indicating that Notch is an essential modulator of tumorigenesis induced by nuclear beta-catenin. We show that this mechanism is operating in human tumors from Familial Adenomatous Polyposis patients. We conclude that Notch activation, accomplished by beta-catenin-mediated up-regulation of Jagged1, is required for tumorigenesis in the intestine. The Notch-specific genetic signature is sufficient to block differentiation and promote vasculogenesis in tumors whereas proliferation depends on both pathways.

  15. Notch pathway activation targets AML-initiating cell homeostasis and differentiation.

    Science.gov (United States)

    Lobry, Camille; Ntziachristos, Panagiotis; Ndiaye-Lobry, Delphine; Oh, Philmo; Cimmino, Luisa; Zhu, Nan; Araldi, Elisa; Hu, Wenhuo; Freund, Jacquelyn; Abdel-Wahab, Omar; Ibrahim, Sherif; Skokos, Dimitris; Armstrong, Scott A; Levine, Ross L; Park, Christopher Y; Aifantis, Iannis

    2013-02-11

    Notch signaling pathway activation is known to contribute to the pathogenesis of a spectrum of human malignancies, including T cell leukemia. However, recent studies have implicated the Notch pathway as a tumor suppressor in myeloproliferative neoplasms and several solid tumors. Here we report a novel tumor suppressor role for Notch signaling in acute myeloid leukemia (AML) and demonstrate that Notch pathway activation could represent a therapeutic strategy in this disease. We show that Notch signaling is silenced in human AML samples, as well as in AML-initiating cells in an animal model of the disease. In vivo activation of Notch signaling using genetic Notch gain of function models or in vitro using synthetic Notch ligand induces rapid cell cycle arrest, differentiation, and apoptosis of AML-initiating cells. Moreover, we demonstrate that Notch inactivation cooperates in vivo with loss of the myeloid tumor suppressor Tet2 to induce AML-like disease. These data demonstrate a novel tumor suppressor role for Notch signaling in AML and elucidate the potential therapeutic use of Notch receptor agonists in the treatment of this devastating leukemia.

  16. Notch1 augments intracellular trafficking of adeno-associated virus type 2.

    Science.gov (United States)

    Ren, Changchun; White, April F; Ponnazhagan, Selvarangan

    2007-02-01

    We report here the significance of the Notch1 receptor in intracellular trafficking of recombinant adeno-associated virus type 2 (rAAV2). RNA profiling of human prostate cancer cell lines with various degrees of AAV transduction indicated a correlation of the amount of Notch1 with rAAV transgene expression. A definitive role of Notch1 in enhancing AAV transduction was confirmed by developing clonal derivatives of DU145 cells overexpressing either full-length or intracellular Notch1. To discern stages of AAV2 transduction influenced by Notch1, competitive binding with soluble heparin and Notch1 antibody, intracellular trafficking using Cy3-labeled rAAV2, and blocking assays for proteasome and dynamin pathways were performed. Results indicated that in the absence or low-level expression of Notch1, only binding of virus was found on the cell surface and internalization was impaired. However, increased Notch1 expression in these cells allowed efficient perinuclear accumulation of labeled capsids. Nuclear transport of the vector was evident by transgene expression and real-time PCR analyses. Dynamin levels were not found to be different among these cell lines, but blocking dynamin function abrogated AAV2 transduction in DU145 clones overexpressing full-length Notch1 but not in clones overexpressing intracellular Notch1. These studies provide evidence for the role of activated Notch1 in intracellular trafficking of AAV2, which may have implications in the optimal use of AAV2 in human gene therapy.

  17. OSM-11 facilitates LIN-12 Notch signaling during Caenorhabditis elegans vulval development.

    Directory of Open Access Journals (Sweden)

    Hidetoshi Komatsu

    2008-08-01

    Full Text Available Notch signaling is critical for cell fate decisions during development. Caenorhabditis elegans and vertebrate Notch ligands are more diverse than classical Drosophila Notch ligands, suggesting possible functional complexities. Here, we describe a developmental role in Notch signaling for OSM-11, which has been previously implicated in defecation and osmotic resistance in C. elegans. We find that complete loss of OSM-11 causes defects in vulval precursor cell (VPC fate specification during vulval development consistent with decreased Notch signaling. OSM-11 is a secreted, diffusible protein that, like previously described C. elegans Delta, Serrate, and LAG-2 (DSL ligands, can interact with the lineage defective-12 (LIN-12 Notch receptor extracellular domain. Additionally, OSM-11 and similar C. elegans proteins share a common motif with Notch ligands from other species in a sequence defined here as the Delta and OSM-11 (DOS motif. osm-11 loss-of-function defects in vulval development are exacerbated by loss of other DOS-motif genes or by loss of the Notch ligand DSL-1, suggesting that DOS-motif and DSL proteins act together to activate Notch signaling in vivo. The mammalian DOS-motif protein Deltalike1 (DLK1 can substitute for OSM-11 in C. elegans development, suggesting that DOS-motif function is conserved across species. We hypothesize that C. elegans OSM-11 and homologous proteins act as coactivators for Notch receptors, allowing precise regulation of Notch receptor signaling in developmental programs in both vertebrates and invertebrates.

  18. Notch and TGFβ form a positive regulatory loop and regulate EMT in epithelial ovarian cancer cells.

    Science.gov (United States)

    Zhou, Jiesi; Jain, Saket; Azad, Abul K; Xu, Xia; Yu, Hai Chuan; Xu, Zhihua; Godbout, Roseline; Fu, YangXin

    2016-08-01

    Epithelial-mesenchymal transition (EMT) plays a critical role in the progression of epithelial ovarian cancer (EOC). However, the mechanisms that regulate EMT in EOC are not fully understood. Here, we report that activation of Notch1 induces EMT in EOC cells as evidenced by downregulation of E-cadherin and cytokeratins, upregulation of Slug and Snail, as well as morphological changes. Interestingly, activation of Notch1 increases TGFβ/Smad signaling by upregulating the expression of TGFβ and TGFβ type 1 receptor. Time course experiments demonstrate that inhibition of Notch by DAPT (a γ-secretase inhibitor) decreases TGFβ-induced phosphorylation of receptor Smads at late, but not at early, timepoints. These results suggest that Notch activation plays a role in sustaining TGFβ/Smad signaling in EOC cells. Furthermore, inhibition of Notch by DAPT decreases TGFβ induction of Slug and repression of E-cadherin and knockdown of Notch1 decreases TGFβ-induced repression of E-cadherin, indicating that Notch is required, at least in part, for TGFβ-induced EMT in EOC cells. On the other hand, TGFβ treatment increases the expression of Notch ligand Jagged1 and Notch target gene HES1 in EOC cells. Functionally, the combination of Notch1 activation and TGFβ treatment is more potent in promoting motility and migration of EOC cells than either stimulation alone. Taken together, our results indicate that Notch and TGFβ form a reciprocal positive regulatory loop and cooperatively regulate EMT and promote EOC cell motility and migration.

  19. Blockage of Notch Signaling Inhibits the Migration and Proliferation of Retinal Pigment Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Weiwei Liu

    2013-01-01

    Full Text Available The Notch signaling is an evolutionarily conserved cell-cell communication pathway that plays critical roles in the proliferation, survival, apoptosis, and fate determination of mammalian cells. Retinal pigment epithelial (RPE cells are responsible for supporting the function of the neural retina and maintaining vision. This study investigated the function of Notch signaling in RPE cells. We found that the members of the Notch signaling pathway components were differentially expressed in RPE cells. Furthermore, blockage of Notch signaling inhibited the migration and proliferation of RPE cells and reduced the expression levels of certain Notch signaling target genes, including HES1, MYC, HEY2, and SOX9. Our data reveal a critical role of Notch signaling in RPE cells, suggesting that targeting Notch signaling may provide a novel approach for the treatment of ophthalmic diseases related to RPE cells.

  20. Evidence of Aortopathy in Mice with Haploinsufficiency of Notch1 in Nos3-Null Background.

    Science.gov (United States)

    Koenig, Sara N; Bosse, Kevin M; Nadorlik, Holly A; Lilly, Brenda; Garg, Vidu

    Thoracic aortic aneurysms (TAA) are a significant cause of morbidity and mortality in humans. While the exact etiology is unknown, genetic factors play an important role. Mutations in NOTCH1 have been linked to bicuspid aortic valve (BAV) and aortopathy in humans. The aim of this study was to determine if haploinsufficiency of Notch1 contributes to aortopathy using Notch1(+/-); Nos3(-/-) mice. Echocardiographic analysis of Notch1(+/-); Nos3(-/-) mice reveals effacement of the sinotubular junction and a trend toward dilation of the aortic sinus. Furthermore, examination of the proximal aorta of Notch1(+/-); Nos3(-/-) mice reveals elastic fiber degradation, a trend toward increased matrix metalloproteinase 2 expression, and increased smooth muscle cell apoptosis, features characteristic of aneurysmal disease. Although at a lower penetrance, we also found features consistent with aortopathic changes in Notch1 heterozygote mice and in Nos3-null mice. Our findings implicate a novel role for Notch1 in aortopathy of the proximal aorta.

  1. Light-induced Notch activity controls neurogenic and gliogenic potential of neural progenitors.

    Science.gov (United States)

    Kim, Kyung-Tai; Song, Mi-Ryoung

    2016-10-28

    Oscillations in Notch signaling are essential for reserving neural progenitors for cellular diversity in developing brains. Thus, steady and prolonged overactivation of Notch signaling is not suitable for generating neurons. To acquire greater temporal control of Notch activity and mimic endogenous oscillating signals, here we adopted a light-inducible transgene system to induce active form of Notch NICD in neural progenitors. Alternating Notch activity saved more progenitors that are prone to produce neurons creating larger number of mixed clones with neurons and progenitors in vitro, compared to groups with no light or continuous light stimulus. Furthermore, more upper layer neurons and astrocytes arose upon intermittent Notch activity, indicating that dynamic Notch activity maintains neural progeny and fine-tune neuron-glia diversity.

  2. Autophagy is involved in mouse kidney development and podocyte differentiation regulated by Notch signalling.

    Science.gov (United States)

    Zhang, Chuyue; Li, Wen; Wen, Junkai; Yang, Zhuo

    2017-02-03

    Podocyte dysfunction results in glomerular diseases accounted for 90% of end-stage kidney disease. The evolutionarily conserved Notch signalling makes a crucial contribution in podocyte development and function. However, the underlying mechanism of Notch pathway modulating podocyte differentiation remains less obvious. Autophagy, reported to be related with Notch signalling pathways in different animal models, is regarded as a possible participant during podocyte differentiation. Here, we found the dynamic changes of Notch1 were coincided with autophagy: they both increased during kidney development and podocyte differentiation. Intriguingly, when Notch signalling was down-regulated by DAPT, autophagy was greatly diminished, and differentiation was also impaired. Further, to better understand the relationship between Notch signalling and autophagy in podocyte differentiation, rapamycin was added to enhance autophagy levels in DAPT-treated cells, and as a result, nephrin was recovered and DAPT-induced injury was ameliorated. Therefore, we put forward that autophagy is involved in kidney development and podocyte differentiation regulated by Notch signalling.

  3. Jets with Variable R

    CERN Document Server

    Krohn, David; Wang, Lian-Tao

    2009-01-01

    We introduce a new class of jet algorithms designed to return conical jets with a variable Delta R radius. A specific example, in which Delta R scales as 1/pT, proves particularly useful in capturing the kinematic features of a wide variety of hard scattering processes. We implement this Delta R scaling in a sequential recombination algorithm and test it by reconstructing resonance masses and kinematic endpoints. These test cases show 10-20% improvements in signal efficiency compared to fixed Delta R algorithms. We also comment on cuts useful in reducing continuum jet backgrounds.

  4. CRITICALITY CURVES FOR PLUTONIUM HYDRAULIC FLUID MIXTURES

    Energy Technology Data Exchange (ETDEWEB)

    WITTEKIND WD

    2007-10-03

    This Calculation Note performs and documents MCNP criticality calculations for plutonium (100% {sup 239}Pu) hydraulic fluid mixtures. Spherical geometry was used for these generalized criticality safety calculations and three geometries of neutron reflection are: {sm_bullet}bare, {sm_bullet}1 inch of hydraulic fluid, or {sm_bullet}12 inches of hydraulic fluid. This document shows the critical volume and critical mass for various concentrations of plutonium in hydraulic fluid. Between 1 and 2 gallons of hydraulic fluid were discovered in the bottom of HA-23S. This HA-23S hydraulic fluid was reported by engineering to be Fyrquel 220. The hydraulic fluid in GLovebox HA-23S is Fyrquel 220 which contains phosphorus. Critical spherical geometry in air is calculated with 0 in., 1 in., or 12 inches hydraulic fluid reflection.

  5. DCS Hydraulics Submittal, Butler County, Alabama, USA

    Data.gov (United States)

    Federal Emergency Management Agency, Department of Homeland Security — Hydraulics data includes spatial datasets and data tables necessary for documenting the hydraulic procedures for computing flood elevations for a flood insurance...

  6. DCS Hydraulics Submittal, Bullock County, Alabama, USA

    Data.gov (United States)

    Federal Emergency Management Agency, Department of Homeland Security — Hydraulics data includes spatial datasets and data tables necessary for documenting the hydraulic procedures for computing flood elevations for a flood insurance...

  7. DCS Hydraulics Submittal, Covington County, Alabama, USA

    Data.gov (United States)

    Federal Emergency Management Agency, Department of Homeland Security — Hydraulics data includes spatial datasets and data tables necessary for documenting the hydraulic procedures for computing flood elevations for a flood insurance...

  8. Notch pathway activation is associated with pancreatic cancer treatment failure.

    Science.gov (United States)

    Lee, Jin Young; Song, Si Young; Park, Jeong Youp

    2014-01-01

    Pancreatic cancer is resistant to conventional treatment. The aim of the study was to confirm the hypothesis that changes in cancer stem cells (CSCs) and developmental pathway after treatment was responsible for treatment failure in pancreatic cancer. After recovery from a gemcitabine treatment, the percentage of pancreatic cancer CSCs and Notch pathway in BxPC3 and HPAC pancreatic cancer cell lines were analyzed by FACS (CD24 and CD44) and western blot (Notch1, Hes1, β-catenin, and pAKT). The effect of DAPT, a gamma-secretase inhibitor, was similarly investigated. The association between immunohistochemical expression of Hes1 and survival was analyzed. The percentage of CD24(+)CD44(+) cells was higher in gemcitabine-treated BxPC3 and HPAC cells than at pre-treatment. CD24(+)CD44(+) cells sorted from the gemcitabine-treated cell lines showed higher migration and invasion ability than CD24(-)CD44(-) or CD24(-)CD44(+) cells from the same cell lines. Western blot analysis showed an increased expression of Notch1 and Hes1 in gemcitabine-treated cell lines. The overall survival of pancreatic cancer patients with strong expression of Hes1 was shorter than that in patients with no or weak expression (11.1 vs. 21.6 months, P = 0.036). Treatment with DAPT reversed the increase in Hes1, β-catenin, and pAKT expression and the proportion of CD24(+)CD44(+) cells in gemcitabine-treated cell lines. The treatment also decreased migration and invasion ability. Our data suggested that an increase in CSCs and activation of the Notch pathway might contribute to the failure of treatment in pancreatic cancer. Notch pathway can be a potential target to overcome treatment failure. Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  9. Experimental and analytical studies of melt jet-coolant interactions: a synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Dinh, T.N.; Bui, V.A.; Nourgaliev, R.R.; Green, J.A.; Sehgal, B.R. [Royal Inst. of Tech., Stockholm (Sweden). Div. of Nuclear Power Safety

    1998-01-01

    Instability and fragmentation of a core melt jet in water have been actively studied during the past ten years. Several models, and a few computer codes, have been developed. However, there are, still, large uncertainties, both, in interpreting experimental results and in predicting reactor-scale processes. Steam explosion and debris coolability, as reactor safety issues, are related to the jet fragmentation process. A better understanding of the physics of jet instability and fragmentation is crucial for assessments of fuel-coolant interactions (FCIs). This paper presents research, conducted at the Division of Nuclear Power Safety, Royal Institute of Technology (RIT/NPS), Stockholm, concerning molten jet-coolant interactions, as a precursor for premixing. First, observations were obtained from scoping experiments with simulant fluids. Second, the linear perturbation method was extended and applied to analyze the interfacial-instability characteristics. Third, two innovative approachs to CFD modeling of jet fragmentation were developed and employed for analysis. The focus of the studies was placed on (a) identifying potential factors, which may affect the jet instability, (b) determining the scaling laws, and (c) predicting the jet behavior for severe accidents conditions. In particular, the effects of melt physical properties, and the thermal hydraulics of the mixing zone, on jet fragmentation were investigated. Finally, with the insights gained from a synthesis of the experimental results and analysis results, a new phenomenological concept, named `macrointeractions concept of jet fragmentation` is proposed. (author)

  10. No evidence for a functional role of bi-directional Notch signaling during angiogenesis.

    Directory of Open Access Journals (Sweden)

    Sven S Liebler

    Full Text Available The Delta-Notch pathway is a signal exchanger between adjacent cells to regulate numerous differentiation steps during embryonic development. Blood vessel formation by sprouting angiogenesis requires high expression of the Notch ligand DLL4 in the leading tip cell, while Notch receptors in the trailing stalk cells are activated by DLL4 to achieve strong Notch signaling activity. Upon ligand binding, Notch receptors are cleaved by ADAM proteases and gamma-secretase. This releases the intracellular Notch domain that acts as a transcription factor. There is evidence that also Notch ligands (DLL1, DLL4, JAG1, JAG2 are processed upon receptor binding to influence transcription in the ligand-expressing cell. Thus, the existence of bi-directional Delta-Notch signaling has been proposed. We report here that the Notch ligands DLL1 and JAG1 are processed in endothelial cells in a gamma-secretase-dependent manner and that the intracellular ligand domains accumulate in the cell nucleus. Overexpression of JAG1 intracellular domain (ICD as well as DLL1-ICD, DLL4-ICD and NOTCH1-ICD inhibited endothelial proliferation. Whereas NOTCH1-ICD strongly repressed endothelial migration and sprouting angiogenesis, JAG1-ICD, DLL1-ICD and DLL4-ICD had no significant effects. Consistently, global gene expression patterns were only marginally affected by the processed Notch ligands. In addition to its effects as a transcription factor, NOTCH1-ICD promotes cell adhesion to the extracellular matrix in a transcription-independent manner. However, JAG1-ICD, DLL1-ICD and DLL4-ICD did not influence endothelial cell adhesion. In summary, reverse signaling of Notch ligands appears to be dispensable for angiogenesis in cellular systems.

  11. High Pressure Hydraulic Distribution System

    Science.gov (United States)

    1991-05-20

    to 500 0 F. 5 cycles. 5000 F room temperature to 50001F; 45 ______________ Icycles The tesis planned for the distribution system demonstrator were...American Society for Testing and Materials ASTM D412 - Tension Testing of Vulcanized Rubber ASTM D571 - Testing Automotive Hydraulic Brake Hose Society of

  12. Hydraulic fracturing system and method

    Energy Technology Data Exchange (ETDEWEB)

    Ciezobka, Jordan; Salehi, Iraj

    2017-02-28

    A hydraulic fracturing system and method for enhancing effective permeability of earth formations to increase hydrocarbon production, enhance operation efficiency by reducing fluid entry friction due to tortuosity and perforation, and to open perforations that are either unopened or not effective using traditional techniques, by varying a pump rate and/or a flow rate to a wellbore.

  13. Hydraulic jumps in a channel

    DEFF Research Database (Denmark)

    Bonn, D.; Andersen, Anders Peter; Bohr, Tomas

    2009-01-01

    We present a study of hydraulic jumps with flow predominantly in one direction, created either by confining the flow to a narrow channel with parallel walls or by providing an inflow in the form of a narrow sheet. In the channel flow, we find a linear height profile upstream of the jump as expected...

  14. Hydraulic Fracture Containment in Sand

    NARCIS (Netherlands)

    Dong, Y.

    2010-01-01

    The mechanism of hydraulic fracturing in soft, high permeability material is considered fundamentally different from that in hard, low permeability rock, where a tensile fracture is created and conventional linear elastic fracture mechanics (LEFM) applies. The fracturing and associated modeling work

  15. Design of hydraulic recuperation unit

    Directory of Open Access Journals (Sweden)

    Jandourek Pavel

    2016-01-01

    Full Text Available This article deals with design and measurement of hydraulic recuperation unit. Recuperation unit consist of radial turbine and axial pump, which are coupled on the same shaft. Speed of shaft with impellers are 6000 1/min. For economic reasons, is design of recuperation unit performed using commercially manufactured propellers.

  16. Tree Hydraulics: How Sap Rises

    Science.gov (United States)

    Denny, Mark

    2012-01-01

    Trees transport water from roots to crown--a height that can exceed 100 m. The physics of tree hydraulics can be conveyed with simple fluid dynamics based upon the Hagen-Poiseuille equation and Murray's law. Here the conduit structure is modelled as conical pipes and as branching pipes. The force required to lift sap is generated mostly by…

  17. Tree Hydraulics: How Sap Rises

    Science.gov (United States)

    Denny, Mark

    2012-01-01

    Trees transport water from roots to crown--a height that can exceed 100 m. The physics of tree hydraulics can be conveyed with simple fluid dynamics based upon the Hagen-Poiseuille equation and Murray's law. Here the conduit structure is modelled as conical pipes and as branching pipes. The force required to lift sap is generated mostly by…

  18. A new linear type hydraulic motor

    Science.gov (United States)

    Jiang, Dong; Zhang, Tong; Li, Wenhua; Chen, Xinyang

    2017-08-01

    This paper proposes the design of liner type hydraulic motor on the base of inner curved radial piston hydraulic motor. The hydraulic cylinders of the new type motor are in the straight line which will improve the utilization of the axial space and different out power can be supplied by changes the number of cylinders. In this paper, the structure and working principle of the liner type hydraulic motor is introduced.

  19. Myc is a Notch1 transcriptional target and a requisite for Notch1-induced mammary tumorigenesis in mice.

    Science.gov (United States)

    Klinakis, Apostolos; Szabolcs, Matthias; Politi, Katerina; Kiaris, Hippokratis; Artavanis-Tsakonas, Spyros; Efstratiadis, Argiris

    2006-06-13

    To explore the potential involvement of aberrant Notch1 signaling in breast cancer pathogenesis, we have used a transgenic mouse model. In these animals, mouse mammary tumor virus LTR-driven expression of the constitutively active intracellular domain of the Notch1 receptor (N1(IC)) causes development of lactation-dependent mammary tumors that regress upon gland involution but progress to nonregressing, invasive adenocarcinomas in subsequent pregnancies. Up-regulation of Myc in these tumors prompted a genetic investigation of a potential Notch1/Myc functional relationship in breast carcinogenesis. Conditional ablation of Myc in the mammary epithelium prevented the induction of regressing N1(IC) neoplasms and also reduced the incidence of nonregressing carcinomas, which developed with significantly increased latency. Molecular analyses revealed that both the mouse and human Myc genes are direct transcriptional targets of N1(IC) acting through its downstream Cbf1 transcriptional effector. Consistent with this mechanistic link, Notch1 and Myc expression is positively correlated by immunostaining in 38% of examined human breast carcinomas.

  20. Hydraulic characterization of " Furcraea andina

    Science.gov (United States)

    Rivera-Velasquez, M. F.; Fallico, C.; Molinari, A.; Santillan, P.; Salazar, M.

    2012-04-01

    The present level of pollution, increasingly involving groundwaters, constitutes a serious risk for environment and human health. Therefore the remediation of saturated and unsaturated soils, removing pollutant materials through innovative and economic bio-remediation techniques is more frequently required. Recent studies on natural fiber development have shown the effectiveness of these fibers for removal of some heavy metals, due to the lignin content in the natural fibers which plays an important role in the adsorption of metal cations (Lee et al., 2004; Troisi et al., 2008; C. Fallico, 2010). In the context of remediation techniques for unsaturated and/or saturated zone, an experimental approach for the hydraulic characterization of the "Furcraea andina" (i.e., Cabuya Blanca) fiber was carried out. This fiber is native to Andean regions and grows easily in wild or cultivated form in the valleys and hillsides of Colombia, Ecuador, and Peru. Fibers of "Furcraea andina" were characterized by experimental tests to determine their hydraulic conductivity or permeability and porosity in order to use this medium for bioremediation of contaminated aquifer exploiting the physical, chemical and microbial capacity of natural fiber in heavy metal adsorption. To evaluate empirically the hydraulic conductivity, laboratory tests were carried out at constant head specifically on the fibers manually extracted. For these tests we used a flow cell (used as permeameter), containing the "Furcraea andina" fibers to be characterized, suitably connected by a tygon pipe to a Marriott's bottle, which had a plastic tube that allow the adjustment of the hydraulic head for different tests to a constant value. By this experiment it was also possible to identify relationships that enable the estimation of permeability as a function of density, i.e. of the compaction degree of the fibers. Our study was carried out for three values of hydraulic head (H), namely 10, 18, and 25 cm and for each

  1. Inhibition of fibroblast growth by Notch1 signaling is mediated by induction of Wnt11-dependent WISP-1.

    Directory of Open Access Journals (Sweden)

    Zhao-Jun Liu

    Full Text Available Fibroblasts are an integral component of stroma and important source of growth factors and extracellular matrix (ECM. They play a prominent role in maintaining tissue homeostasis and in wound healing and tumor growth. Notch signaling regulates biological function in a variety of cells. To elucidate the physiological function of Notch signaling in fibroblasts, we ablated Notch1 in mouse (Notch1(Flox/Flox embryonic fibroblasts (MEFs. Notch1-deficient (Notch1(-/- MEFs displayed faster growth and motility rate compared to Notch1(Flox/Flox MEFs. Such phenotypic changes, however, were reversible by reconstitution of Notch1 activation via overexpression of the intracellular domain of Notch1 (NICD1 in Notch1-deficient MEFs. In contrast, constitutive activation of Notch1 signaling by introducing NICD1 into primary human dermal fibroblasts (FF2441, which caused pan-Notch activation, inhibited cell growth and motility, whereas cellular inhibition was relievable when the Notch activation was countered with dominant-negative mutant of Master-mind like 1 (DN-MAML-1. Functionally, "Notch-activated" stromal fibroblasts could inhibit tumor cell growth/invasion. Moreover, Notch activation induced expression of Wnt-induced secreted proteins-1 (WISP-1/CCN4 in FF2441 cells while deletion of Notch1 in MEFs resulted in an opposite effect. Notably, WISP-1 suppressed fibroblast proliferation, and was responsible for mediating Notch1's inhibitory effect since siRNA-mediated blockade of WISP-1 expression could relieve cell growth inhibition. Notch1-induced WISP-1 expression appeared to be Wnt11-dependent, but Wnt1-independent. Blockade of Wnt11 expression resulted in decreased WISP-1 expression and liberated Notch-induced cell growth inhibition. These findings indicated that inhibition of fibroblast proliferation by Notch pathway activation is mediated, at least in part, through regulating Wnt1-independent, but Wnt11-dependent WISP-1 expression.

  2. The NOTCH signaling pathway: role in the pathogenesis of T-cell acute lymphoblastic leukemia and implication for therapy

    OpenAIRE

    2013-01-01

    T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) is characterized by aberrant activation of NOTCH1 in over 60% of T-ALL cases. The high prevalence of activating NOTCH1 mutations highlights the critical role of NOTCH signaling in the pathogenesis of this disease and has prompted the development of therapeutic approaches targeting the NOTCH signaling pathway. Small molecule gamma secretase inhibitors (GSIs) can effectively inhibit oncogenic NOTCH1 and are in clinical testing for the treatme...

  3. Measurements of Jets in ALICE

    CERN Document Server

    Nattrass, Christine

    2016-01-01

    The ALICE detector can be used for measurements of jets in pp , p Pb, and Pb–Pb collisions. Measurements of jets in pp collisions are consis- tent with expectations from perturbative calculations and jets in p Pb scale with the number of nucleon–nucleon collisions, indicating that cold nuclear matter effects are not observed for jets. Measurements in Pb–Pb collisions demonstrate suppression of jets relative to expectations from binary scaling to the equivalent number of nucleon–nucleon collisions

  4. 14 CFR 25.1435 - Hydraulic systems.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Hydraulic systems. 25.1435 Section 25.1435... STANDARDS: TRANSPORT CATEGORY AIRPLANES Equipment Miscellaneous Equipment § 25.1435 Hydraulic systems. (a) Element design. Each element of the hydraulic system must be designed to: (1) Withstand the proof...

  5. 14 CFR 27.1435 - Hydraulic systems.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Hydraulic systems. 27.1435 Section 27.1435... STANDARDS: NORMAL CATEGORY ROTORCRAFT Equipment Safety Equipment § 27.1435 Hydraulic systems. (a) Design. Each hydraulic system and its elements must withstand, without yielding, any structural loads...

  6. Astrophysics: Cosmic jet engines

    Science.gov (United States)

    Young, Andy

    2010-02-01

    In some galaxies, matter falling onto a supermassive black hole is ejected in narrow jets moving at close to the speed of light. New observations provide insight into the workings of these cosmic accelerators.

  7. Jet lag prevention

    Science.gov (United States)

    ... medlineplus.gov/ency/patientinstructions/000719.htm Jet lag prevention To use the sharing features on this page, ... Headache Irritability Stomach upset Sore muscles Tips for Prevention Before your trip: Get plenty of rest, eat ...

  8. Jet Engine Noise Reduction

    Science.gov (United States)

    2009-04-01

    Technology Solutions, Lockheed Martin Robert S. Carnes , M.D. NRAC Member, Battelle Memorial Institute MajGen Paul A. Fratarangelo, USMC (Ret) NRAC...Development, Acquisition) (VADM Architzel). The Naval Research Advisory Committee members (Bowes, Bowler, Carnes and Fratarangelo) have broad...Lockheed Martin ADP Boeing: Jet Engine Noise Reduction for Tactical Fighter Aircraft Mr. Tom Kaemming, K. Viswanathan, Ph . D. Tactical Jet Noise

  9. CFD study of turbulent jet impingement on curved surface

    Institute of Scientific and Technical Information of China (English)

    Javad Taghinia; Md Mizanur Rahman; Timo Siikonen

    2016-01-01

    The heat transfer and flow characteristics of air jet impingement on a curved surface are investigated with com-putational fluid dynamics (CFD) approach. The first applied model is a one-equation SGS model for large eddy simulation (LES) and the second one is the SST-SAS hybrid RANS-LES. These models are utilized to study the flow physics in impinging process on a curved surface for different jet-to-surface (h/B) distances at two Reynolds numbers namely, 2960 and 4740 based on the jet exit velocity (Ue) and the hydraulic diameter (2B). The predic-tions are compared with the experimental data in the literature and also the results from RANS k-εmodel. Com-parisons show that both models can produce relatively good results. However, one-equation model (OEM) produced more accurate results especial y at impingement region at lower jet-to-surface distances. In terms of heat transfer, the OEM also predicted better at different jet-to-surface spacings. It is also observed that both models show similar performance at higher h/B ratios.

  10. Jets and QCD

    CERN Document Server

    Ali, Ahmed

    2010-01-01

    The observation of quark and gluon jets has played a crucial role in establishing Quantum Chromodynamics [QCD] as the theory of the strong interactions within the Standard Model of particle physics. The jets, narrowly collimated bundles of hadrons, reflect configurations of quarks and gluons at short distances. Thus, by analysing energy and angular distributions of the jets experimentally, the properties of the basic constituents of matter and the strong forces acting between them can be explored. In this review we summarise the properties of quark and gluon jets and the impact of their observation on Quantum Chromodynamics, primarily the discovery of the gluons as the carriers of the strong force. Focusing on these basic points, jets in $e^+ e^-$ collisions will be in the foreground of the discussion. In addition we will delineate the role of jets as tools for exploring other particle aspects in $ep$ and $pp/p\\bar{p}$ collisions - quark and gluon densities in protons, measurements of the QCD coupling, fundam...

  11. Jet engine. Strahltriebwerk

    Energy Technology Data Exchange (ETDEWEB)

    Weber, F.J.

    1990-11-15

    A gas turbine axial-flow compressor aggregate is mounted in a jet engine consisting of a high-temperature combustion chamber that is composed of conical rings forming slits and set together to a ring column and reaches up to the propelling nozzle, a compressed-air generator supplying the jet engine with compressed air at subsonic speeds and running into the propelling nozzle and a shell encasing the jet engine while leaving a certain intermediate space. The compressor aggregate has a relatively high fuel consumption and high emission rates, involves high production and maintenance costs and puts the blades at a high risk of overheating. The problem basic to the invention was to install a compressed-air generator in the jet engine that has lower fuel consumption and emission rates and is cheaper to manufacture and to service. The invention provides free-piston compressors for compressed-air generators arranged in a circle around the central high-temperature combustion chamber. The ring of compressors can rotate on bearings against the jet engine shell, so that each compressor can be turned to the bottom and serviced there. The jet engine is suitable as an engine for supersonic aircraft.

  12. Jet Mass Spectra in Higgs + One Jet at NNLL

    CERN Document Server

    Jouttenus, Teppo T; Tackmann, Frank J; Waalewijn, Wouter J

    2013-01-01

    The invariant mass of a jet is a benchmark variable describing the structure of jets at the LHC. We calculate the jet mass spectrum for Higgs plus one jet at the LHC at next-to-next-to-leading logarithmic (NNLL) order using a factorization formula. At this order, the cross section becomes sensitive to perturbation theory at the soft m_jet^2/p_T^jet scale. Our calculation is exclusive and uses the 1-jettiness global event shape to implement a veto on additional jets. The dominant dependence on the jet veto is removed by normalizing the spectrum, leaving residual dependence from non-global logarithms depending on the ratio of the jet mass and jet veto variables. For our exclusive jet cross section these non-global logarithms are parametrically smaller than in the inclusive case, allowing us to obtain a complete NNLL result. Results for the dependence of the jet mass spectrum on the kinematics, jet algorithm, and jet size R are given. Using individual partonic channels we illustrate the difference between the je...

  13. Three-dimensional evolution of flow structures in transitional circular and chevron jets

    Science.gov (United States)

    Violato, Daniele; Scarano, Fulvio

    2011-12-01

    The three-dimensional behavior of flow transition in circular and 6-chevron jets at Re = 5000 is investigated with experiments conducted on a free water jet by time-resolved tomographic particle image velocimetry. The emphasis is on the unsteady organization of coherent flow structures, which play a role in the generation of acoustic noise. Shedding and pairing of vortices are the most pronounced phenomena observed in the near field of the circular jet. The first and second pairing amplify the axial pulsatile motion in the jet column and lead to the growth of azimuthal waves culminating in the breakup of the vortex ring. Streamwise vortices of axial and radial vorticity are observed in the outer region and move inward and outward under the effect of the vortex rings. In the jet with chevrons, the axisymmetric ring-like coherence of the circular jet is not encountered. Instead, streamwise flow structures of azimuthal vorticity emanate from the chevron apices, and counter-rotating streamwise vortices of axial and radial vorticity develop from the chevron notches. The decay of streamwise vortices is accompanied by the formation of C-shaped structures. The three-dimensional analysis allows quantifying the vortex stretching and tilting activity, which, for the circular jet exit, is related to the azimuthal instabilities and the streamwise vortices connecting the vortex rings. In the chevron jet, stretching and tilting peak during the formation of C-structures. Following Powell's aeroacoustic analogy, the spatial distribution of the source term is mapped, evaluating the temporal derivative of the Lamb vector. The spatio-temporal evolution of such source term is visualized revealing that the events of highest activity are associated with the processes of vortex-ring pairing and vortex-ring disruption for the circular jet, and with the decay of streamwise instabilities and the formation of C-shaped structures for the chevron case.

  14. How the NOTCH pathway contributes to the ability of osteosarcoma cells to metastasize.

    Science.gov (United States)

    Hughes, Dennis P M

    2009-01-01

    Controlling metastasis is the key to improving outcomes for osteosarcoma patients; yet our knowledge of the mechanisms regulating the metastatic process is incomplete. Clearly Fas and Ezrin are important, but other genes must play a role in promoting tumor spread. Early developmental pathways are often recapitulated in malignant tissues, and these genes are likely to be important in regulating the primitive behaviors of tumor cells, including invasion and metastasis. The Notch pathway is a highly conserved regulatory signaling network involved in many developmental processes and several cancers, at times serving as an oncogene and at others, behaving as a tumor suppressor. In normal limb development, Notch signaling maintains the apical ectodermal ridge in the developing limb bud and regulated size of bone and muscles. Here, we examine the role of Notch signaling in promoting metastasis of osteosarcoma, and the underlying regulatory processes that control Notch pathway expression and activity in the disease. We have shown that, compared to normal human osteoblasts and non-metastatic osteosarcoma cell lines, osteosarcoma cell lines with the ability to metastasize have higher levels of Notch 1, Notch 2, the Notch ligand DLL1 and the Notch-induced gene Hes1. When invasive osteosarcoma cells are treated with small molecule inhibitors of gamma-secretase, which blocks Notch activation, invasiveness is abrogated. Direct retroviral expression has shown that Hes1 expression was necessary for osteosarcoma invasiveness and accounted for the observations. In a novel orthotopic murine xenograft model of osteosarcoma pulmonary metastasis, blockade of Hes1 expression and Notch signaling eliminated spread of disease from the tibial primary tumor. In a sample of archival human osteosarcoma tumor specimens, expression of Hes1 mRNA was inversely correlated with survival (n=16 samples, p=0.04). Expression of the microRNA 34 cluster, which is known to downregulate DLL1, Notch 1 and

  15. Clinicopathological significance of altered Notch signaling in extrahepatic cholangiocarcinoma and gallbladder carcinoma

    Institute of Scientific and Technical Information of China (English)

    Hyun Ah Yoon; Myung Hwan Noh; Byung Geun Kim; Ji Sun Han; Jin Seok Jang; Seok Ryeol Choi; Jin Sook Jeong; Jin Ho Chun

    2011-01-01

    AIM: To investigate the role and clinicopathological significance of aberrant expression of Notch receptors and Delta-like ligand-4 (DLL4) in extrahepatic cholangiocarcinoma and gallbladder carcinoma.METHODS: One hundred and ten patients had surgically resected extrahepatic cholangiocarcinoma (CC) and gallbladder carcinoma specimens examined by immunohistochemistry of available paraffin blocks. Immunohistochemistry was performed using anti-Notch receptors 1-4 and anti-DLL4 antibodies. We scored the immunopositivity of Notch receptors and DLL4 expression by percentage of positive tumor cells with cytoplasmic expression and intensity of immunostaining. Coexistent nuclear localization was evaluated. Clinicopathological parameters and survival data were compared with the expression of Notch receptors 1-4 and DLL4.RESULTS: Notch receptor proteins showed in the cytoplasm with or without nuclear expression in cancer cells, as well as showing weak cytoplasmic expression in non-neoplastic cells. By semiquantitative evaluation, positive immunostaining of Notch receptor 1 was detected in 96 cases (87.3%), Notch receptor 2 in 97 (88.2%), Notch receptor 3 in 97 (88.2%), Notch receptor 4 in 103 (93.6), and DLL4 in 84 (76.4%). In addition, coexistent nuclear localization was noted [Notch receptor 1; 18 cases (18.8%), Notch receptor 2; 40 (41.2%), Notch receptor 3; 32 (33.0%), Notch receptor 4; 99 (96.1%), DLL4; 48 (57.1%)]. Notch receptor 1 expression was correlated with advanced tumor, node, metastasis (TNM) stage (P = 0.043), Notch receptor 3 with advanced T stage (P = 0.017), tendency to express in cases with nodal metastasis (P = 0.065) and advanced TNM stage (P = 0.052). DLL4 expression tended to be related to less histological differentiation (P = 0.095). Coexistent nuclear localization of Notch receptor 3 was related to no nodal metastasis (P = 0.027) and Notch receptor 4 with less histological differentiation (P = 0.036), while DLL4 tended to be related inversely with T

  16. Thermal Hydraulic Performance of Tight Lattice Bundle

    Science.gov (United States)

    Yamamoto, Yasushi; Akiba, Miyuki; Morooka, Shinichi; Shirakawa, Kenetsu; Abe, Nobuaki

    Recently, the reduced moderation spectrum BWR has been studied. The fast neutron spectrum is obtained through triangular tight lattice fuel. However, there are few thermal hydraulic test data and thermal hydraulic correlation applicable to critical power prediction in such a tight lattice bundle. This study aims to enhance the database of the thermal hydraulic performance of the tight lattice bundle whose rod gap is about 1mm. Therefore, thermal hydraulic performance measurement tests of tight lattice bundles for the critical power, the pressure drop and the counter current flow limiting were performed. Moreover, the correlations to evaluate the thermal-hydraulic performance of the tight lattice bundle were developed.

  17. Design of hydraulic output Stirling engine

    Science.gov (United States)

    Toscano, W. M.; Harvey, A. C.; Lee, K.

    1983-01-01

    A hydraulic output system for the RE-1000 free piston stirling engine (FPSE) was designed. The hydraulic output system can be readily integrated with the existing hot section of RE-1000 FPSE. The system has two simply supported diaphragms which separate the engine gas from the hydraulic fluid, a dynamic balance mechanism, and a novel, null center band hydraulic pump. The diaphragms are designed to endure more than 10 billion cycles, and to withstand the differential pressure load as high as 14 MPa. The projected thermodynamic performance of the hydraulic output version of RE-1000 FPSE is 1.87 kW at 29/7 percent brake efficiency.

  18. Notch signaling and ghost cell fate in the calcifying cystig odontogenic tumor

    Directory of Open Access Journals (Sweden)

    Siar CH

    2011-11-01

    Full Text Available Abstract Notch signaling is an evolutionarily conserved mechanism that enables adjacent cells to adopt different fates. Ghost cells (GCs are anucleate cells with homogeneous pale eosinophilic cytoplasm and very pale to clear central areas (previous nucleus sites. Although GCs are present in a variety of odontogenic lesions notably the calcifying cystic odontogenic tumor (GCOT, their nature and process of formation remains elusive. The aim of this study was to investigate the role of Notch signaling in the cell fate specification of GCs in CCOT. Immunohistochemical staining for four Notch receptors (Notch1, Notch2, Notch3 and Notch4 and three ligands (Jagged1, Jagged2 and Delta1 was performed on archival tissues of five CCOT cases. Level of positivity was quantified as negative (0, mild (+, moderate (2+ and strong (3+. Results revealed that GCs demonstrated overexpression for Notch1 and Jagged1 suggesting that Notch1Jagged1 signaling might serve as the main transduction mechanism in cell fate decision for GCs in CCOT. Protein localizations were largely membranous and/or cytoplasmic. Mineralized GCs also stained positive implicating that the calcification process might be associated with upregulation of these molecules. The other Notch receptors and ligands were weak to absent in GCs and tumoral epithelium. Stromal endothelium and fibroblasts were stained variably positive.

  19. Temporal Expression of Notch in Preterm Rat Lungs Exposed to Hyperoxia

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To explore the mechanism of Notch in hyperoxia-induced preterm rat lung injury, 2days-old preterm SD rats were randomized into control and hyperoxia group (FiO2 ≥0.85). On day 1, 7, 14 and 21, 8 rat pups of each time point were used to assess histopathological changes of lung with HE staining and to evaluate the expression of Notch1 and Notch3 with immunohistochemistry.Notch1, Notch3, Aquaprin5 (AQP5) and surfactant protein C (SP-C) mRNA were measured by reverse transcription polymerase chain reaction (RT-PCR). The results showed that the lung injury in the hyperoxia group was characterized by retarded lung alveolization and differentiation of alveolar epithelial type Ⅱ cells (AEC Ⅱ ). Positive staining of Notch1 in hyperoxia group was weaker than controls at every time point (except for day 7), while positive staining of Notch3 was much stronger (P<0.05, P<0.01). Notch1, Notch3 mRNA level showed similar change as protein level. AQP5, SP C mRNA decreased significantly as compared with that of the controls (P<0.01).We are led to conclude that hyperoxia results in abnormal expression of Notch, which is likely to contribute to the pathogenesis of lung injury through regulating proliferation and transdifferentiation of alveolar epithelial cells.

  20. The Notch pathway in the annelid Platynereis: insights into chaetogenesis and neurogenesis processes.

    Science.gov (United States)

    Gazave, Eve; Lemaître, Quentin I B; Balavoine, Guillaume

    2017-02-01

    Notch is a key signalling pathway playing multiple and varied functions during development. Notch regulates the selection of cells with a neurogenic fate and maintains a pool of yet uncommitted precursors through lateral inhibition, both in insects and in vertebrates. Here, we explore the functions of Notch in the annelid Platynereis dumerilii (Lophotrochozoa). Conserved components of the pathway are identified and a scenario for their evolution in metazoans is proposed. Unexpectedly, neither Notch nor its ligands are expressed in the neurogenic epithelia of the larva at the time when massive neurogenesis begins. Using chemical inhibitors and neural markers, we demonstrate that Notch plays no major role in the general neurogenesis of larvae. Instead, we find Notch components expressed in nascent chaetal sacs, the organs that produce the annelid bristles. Impairing Notch signalling induces defects in chaetal sac formation, abnormalities in chaetae producing cells and a change of identity of chaeta growth accessory cells. This is the first bilaterian species in which the early neurogenesis processes appear to occur without a major involvement of the Notch pathway. Instead, Notch is co-opted to pattern annelid-specific organs, likely through a lateral inhibition process. These features reinforce the view that Notch signalling has been recruited multiple times in evolution due to its remarkable 'toolkit' nature.

  1. Chemotherapeutic treatment is associated with Notch1 induction in cutaneous T-cell lymphoma.

    Science.gov (United States)

    Kamstrup, Maria R; Biskup, Edyta; Manfè, Valentina; Savorani, Cecilia; Liszewski, Walter; Wirèn, Johan; Specht, Lena; Gniadecki, Robert

    2017-01-01

    The Notch pathway is important for survival of cutaneous T-cell lymphoma (CTCL) cells. We investigated the effect of chemotherapy (doxorubicin, etoposide, and gemcitabine) and radiation modalities on Notch signaling in CTCL cell lines. Chemotherapy induced Notch1 expression at the mRNA and protein level in MyLa2000 and Hut78. Upregulation of well-established Notch targets supported the functional activity of Notch1. Transfection of Notch1 siRNA into MyLa2000 cells was not able to suppress the effects of chemotherapy on Notch1 activation significantly. Notch1 knockdown in combination with doxorubicin, etoposide, or gemcitabine compared to chemotherapy alone decreased cell viability by 12, 20, and 26%, respectively (p < 0.05). Additionally, X-rays (in MyLa2000 but not SeAx) and psoralen plus UVA (PUVA) (in MyLa2000, Hut78, and SeAx) increased the expression of Notch1 family members. Our results indicate that CTCL cells activate the Notch pathway in vitro in response to chemotherapy and radiation modalities as a possible protective mechanism.

  2. Mapping the consequence of Notch1 proteolysis in vivo with NIP-CRE.

    Science.gov (United States)

    Vooijs, Marc; Ong, Chin-Tong; Hadland, Brandon; Huppert, Stacey; Liu, Zhenyi; Korving, Jeroen; van den Born, Maaike; Stappenbeck, Thaddeus; Wu, Yumei; Clevers, Hans; Kopan, Raphael

    2007-02-01

    The four highly conserved Notch receptors receive short-range signals that control many biological processes during development and in adult vertebrate tissues. The involvement of Notch1 signaling in tissue self-renewal is less clear, however. We developed a novel genetic approach N(1)IP-CRE (Notch1 Intramembrane Proteolysis) to follow, at high resolution, the descendents of cells experiencing Notch1 activation in the mouse. By combining N(1)IP-CRE with loss-of-function analysis, Notch activation patterns were correlated with function during development, self-renewal and malignancy in selected tissues. Identification of many known functions of Notch1 throughout development validated the utility of this approach. Importantly, novel roles for Notch1 signaling were identified in heart, vasculature, retina and in the stem cell compartments of self-renewing epithelia. We find that the probability of Notch1 activation in different tissues does not always indicate a requirement for this receptor and that gradients of Notch1 activation are evident within one organ. These findings highlight an underappreciated layer of complexity of Notch signaling in vivo. Moreover, NIP-CRE represents a general strategy applicable for monitoring proteolysis-dependent signaling in vivo.

  3. General IIR optical notch filter based on Michelson Gires-Tournois interferometer

    Science.gov (United States)

    Zhang, Juan; Guo, Sen; Li, Xue

    2012-03-01

    A general IIR optical notch filter design is presented from a digital filter design perspective for Michelson Gires-Tournois Interferometer structure. Optical notch filter with arbitrary notch frequency, notch point number, and 3 dB rejection bandwidth can be designed easily. According to the spectral requirement of desired notch filter, in frequency domain we firstly calculate the transfer function of desired allpass filter. Then the numbers of reflectors in Gires-Tournois etalon can be determined. We calculate the transfer function of this multi-cavity Gires-Tournois etalon by using Z-transform. By making the transfer function of allpass filter in frequency domain equal to that of the multi-cavity Gires-Tournois etalon, the notch filter can be directly realized. Different design examples are given in detail in the paper. The change of output spectrum is also investigated for the reflectance of the reflectors and the distance between the reflectors deviating from the ideal value. The results show that the notch filter has the tunability of notch frequency and 3 dB rejection bandwidth. The chromatic dispersion characteristic of the notch filter is analyzed finally. It shows that the notch filter has excellent chromatic dispersion characteristic.

  4. The Notch pathway is important in maintaining the cancer stem cell population in pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Ethan V Abel

    Full Text Available Pancreatic cancer stem cells (CSCs represent a small subpopulation of pancreatic cancer cells that have the capacity to initiate and propagate tumor formation. However, the mechanisms by which pancreatic CSCs are maintained are not well understood or characterized.Expression of Notch receptors, ligands, and Notch signaling target genes was quantitated in the CSC and non-CSC populations from 8 primary human pancreatic xenografts. A gamma secretase inhibitor (GSI that inhibits the Notch pathway and a shRNA targeting the Notch target gene Hes1 were used to assess the role of the Notch pathway in CSC population maintenance and pancreatic tumor growth.Notch pathway components were found to be upregulated in pancreatic CSCs. Inhibition of the Notch pathway using either a gamma secretase inhibitor or Hes1 shRNA in pancreatic cancer cells reduced the percentage of CSCs and tumorsphere formation. Conversely, activation of the Notch pathway with an exogenous Notch peptide ligand increased the percentage of CSCs as well as tumorsphere formation. In vivo treatment of orthotopic pancreatic tumors in NOD/SCID mice with GSI blocked tumor growth and reduced the CSC population.The Notch signaling pathway is important in maintaining the pancreatic CSC population and is a potential therapeutic target in pancreatic cancer.

  5. The oncogenic roles of Notch1 in astrocytic gliomas in vitro and in vivo.

    Science.gov (United States)

    Xu, Peng; Qiu, Mingzhe; Zhang, Zhiyong; Kang, Chunsheng; Jiang, Rongcai; Jia, Zhifan; Wang, Guangxiu; Jiang, Hao; Pu, Peiyu

    2010-03-01

    Notch receptors play an essential role in cellular processes during embryonic and postnatal development, including maintenance of stem cell self-renewal, proliferation, and determination of cell fate and apoptosis. Deregulation of Notch signaling has been implicated in some genetic diseases and tumorigenesis. The function of Notch signaling in a variety of tumors can be either oncogenic or tumor-suppressive, depending on the cellular context. In this study, Notch1 overexpression was observed in the majority of 45 astrocytic gliomas with different grades and in U251MG glioma cells. Transfection of siRNA targeting Notch1 into U251 cells in vitro downregulated Notch1 expression, associated with inhibition of cell growth, arrest of cell cycle, reduction of cell invasiveness, and induction of cell apoptosis. Meanwhile, tumor growth was delayed in established subcutaneous gliomas in nude mice treated with Notch1 siRNA in vivo. These results suggest that Notch1 plays an important oncogenic role in the development and progression of astrocytic gliomas. Furthermore, knockdown of Notch1 expression by siRNA simultaneously downregulated the expression of EGFR and the important components of its downstream pathways, including PI3K, p-AKT, K-Ras, cyclin D1 and MMP9, indicating the crosstalk and interaction of Notch and EGFR signaling pathways.

  6. In-situ tensile testing of notched poly- and oligocrystalline 316L wires

    Energy Technology Data Exchange (ETDEWEB)

    Mitevski, Bojan [Materials Science and Engineering (ITM), Duisburg (Germany); Weiss, Sabine [Brandenburg Technical Univ., Cottbus-Senftenberg (Germany). Chair of Physical Metallurgy and Materials Science.; Fischer, Alfons [Duisburg-Essen Univ. (Germany). Materials Science and Engineering; Rush Univ. Medical Center, Chicago, IL (United States). Dept. of Orthopedics

    2017-03-01

    In-situ testing inside a scanning electron microscope is a helpful tool for detailed analyses of small sized specimens with respect to their mechanical properties and the correlated microstructural alterations. Thus, this test method is used to analyze the tensional properties of thin 316L (1.4441) wires used for microscale components, e.g., like coronary artery stents. Tensile tests were conducted on unnotched and circularly notched 316L wires (oe 0.95 mm) with a special focus on the number of grains within the cross section as well as the notch geometry. Four combinations of notch width (2 and 4 mm) and notch depth (diameter at notch root: 0.5 and 0.75 mm) were chosen. Notch depth and notch shape were adjusted by means of electrochemical polishing. Previous investigations showed, that oligocrystalline structures exhibit a different mechanical behavior compared to polycrystalline ones or single crystals. There are only a few data available on mechanical testing of oligocrystalline structures with respect to varying notch geometries. Depending on the notch geometry, grain size and, therefore, the number of grains within the notch cross section widely scattering yield- and tensile strength as well as failure elongation values were measured. However, the transition criterion between poly- and oligocrystalline behavior could be quantified to be 6 to 7 grains within the cross section.

  7. Notch signalling drives bone marrow stromal cell-mediated chemoresistance in acute myeloid leukemia.

    Science.gov (United States)

    Takam Kamga, Paul; Bassi, Giulio; Cassaro, Adriana; Midolo, Martina; Di Trapani, Mariano; Gatti, Alessandro; Carusone, Roberta; Resci, Federica; Perbellini, Omar; Gottardi, Michele; Bonifacio, Massimiliano; Nwabo Kamdje, Armel Hervé; Ambrosetti, Achille; Krampera, Mauro

    2016-04-19

    Both preclinical and clinical investigations suggest that Notch signalling is critical for the development of many cancers and for their response to chemotherapy. We previously showed that Notch inhibition abrogates stromal-induced chemoresistance in lymphoid neoplasms. However, the role of Notch in acute myeloid leukemia (AML) and its contribution to the crosstalk between leukemia cells and bone marrow stromal cells remain controversial. Thus, we evaluated the role of the Notch pathway in the proliferation, survival and chemoresistance of AML cells in co-culture with bone marrow mesenchymal stromal cells expanded from both healthy donors (hBM-MSCs) and AML patients (hBM-MSCs*). As compared to hBM-MSCs, hBM-MSCs* showed higher level of Notch1, Jagged1 as well as the main Notch target gene HES1. Notably, hBM-MSCs* induced expression and activation of Notch signalling in AML cells, supporting AML proliferation and being more efficientin inducing AML chemoresistance than hBM-MSCs*. Pharmacological inhibition of Notch using combinations of Notch receptor-blocking antibodies or gamma-secretase inhibitors (GSIs), in presence of chemotherapeutic agents, significant lowered the supportive effect of hBM-MSCs and hBM-MSCs* towards AML cells, by activating apoptotic cascade and reducing protein level of STAT3, AKT and NF-κB.These results suggest that Notch signalling inhibition, by overcoming the stromal-mediated promotion of chemoresistance,may represent a potential therapeutic targetnot only for lymphoid neoplasms, but also for AML.

  8. Notch signalling suppresses regulatory T-cell function in murine experimental autoimmune uveitis.

    Science.gov (United States)

    Rong, Hua; Shen, Hongjie; Xu, Yueli; Yang, Hai

    2016-12-01

    Autoimmune uveitis is an intraocular inflammatory disorder in developed countries. Understanding the mechanisms underlying the development and modulation of immune reaction in uveitic eyes is critical for designing therapeutic interventions. Here we investigated the role of Notch signalling in regulatory T-cell (Treg cell) function during experimental autoimmune uveitis (EAU). Using the Foxp3-GFP reporter mouse strain, the significance of Notch signalling for the function of infiltrating Treg cells was characterized in an EAU model. We found that infiltrating Treg cells substantially expressed Notch-1, Notch-2, JAG1 and DLL1 in uveitic eyes. Activation of Notch signalling, represented by expression of HES1 and HES5, was enhanced in infiltrating Treg cells. Treatment with JAG1 and DLL1 down-regulated Foxp3 expression and immunosuppressive activity of isolated infiltrating Treg cells in vitro, whereas neutralizing antibodies against JAG1 and DLL1 diminished Notch ligand-mediated negative effects on Treg cells. To investigate the significance of Notch signalling for Treg cell function in vivo, lentivirus-derived Notch short hairpin RNAs were transduced into in vitro expanded Treg cells before adoptive transfer of Treg cells into EAU mice. Transfer of Notch-1-deficient Treg cells remarkably reduced pro-inflammatory cytokine production and inflammatory cell infiltration in uveitic eyes. Taken together, Notch signalling negatively modulates the immunosuppressive function of infiltrating Treg cells in mouse EAU.

  9. Research on Disc Spring Buffering the Backward Impact of Piston of Liquid-Jet Hydraulic Hammer Based on LS-DYNA%基于 LS -DYNA 的射流式液动锤活塞回程缓冲结构的研究

    Institute of Scientific and Technical Information of China (English)

    杨冬冬; 李国琳; 纪天坤; 孙强; 彭枧明

    2016-01-01

    为了减弱射流式液动锤活塞回程撞击缸体的应力波对射流元件的破坏,延长射流元件的寿命,提出在缸体中设置碟簧缓冲结构来吸收冲锤回程的冲击能,并应用LS-DYNA显示动力学分析手段,对活塞回程进行仿真分析,探究碟簧缓冲对射流元件受力状态的影响,结果表明:采用碟簧缓冲结构,射流元件的最大应力可降低40%~57%,有效改善了射流元件的应力状态,在液动锤实际工作中具有可行性。%In order to reduce the damage to fluidic element caused by stress waves from impacting cylinder in a return-stroke of the fluidic hydraulic hammer piston to prolong the life of the fluidic element, a disc spring buffer structure in the cylinder was proposed to absorb the striking energy of hammer stroke.The simulation analysis was carried out on the piston return-stroke by the means of LS-DYNA display dynamic analysis to study the effect of the disc spring buffer on the stress state of bi-stable fluidic amplifier.The results show the feasiblility of disc spring buffer structure in the actual work of hy-draulic hammer, the maximum stress can be decreased by 40%~57%in bi-stable fluidic amplifier and the stress state of fluidic element is effectively improved.

  10. Effect of Trastuzumab on Notch-1 Signaling Pathway in Breast Cancer SK-BR3 Cells

    Institute of Scientific and Technical Information of China (English)

    Ming Han; Hua-yu Deng; Rong Jiang

    2012-01-01

    Objective:To investigate the effects and mechanisms of trastuzumab on Notch-1 pathway in breast cancer cells,recognizing the significance of Notch-1 signaling pathway in trastuzumab resistance.Methods:Immunocytochemistry staining and Western blotting were employed to justify the expression of Notch-1 protein in HER2-overexpressing SK-BR3 cells and HER2-non-overexpressing breast cancer MDA-MB-231 cells.Western blotting and reverse transcription PCR (RT-PCR) were used to detect the activated Notch-1 and Notch-1 target gene HES-1 mRNA expression after SK-BR3 cells were treated with trastuzumab.Double immunofluorescence staining and co-immunoprecipitation were used to analyze the relationship of Notch-1 and HER2 proteins.Results:The level of Notch-1 nuclear localization and activated Notch-1 proteins in HER2-overexpressing cells were significantly lower than in HER2-non-overexpressing cells (P<0.01),and the expressions of activated Notch-1 and HES-1 mRNA were obviously increased after trastuzumab treatment (P<1.05),but HER2 expression did not change significantly for trastuzumab treating (P>0.05).Moreover,Notch-1 was discovered to co-localize and interact with HER2 in SK-BR3 cells.Conclusion:Overexpression of HER2 decreased Notch-1 activity by the formation of a HER2-Notch1 complex,and trastuzumab can restore the activity of Notch-1 signaling pathway,which could be associated with cell resistance to trastuzumab.

  11. Drosophila p53 controls Notch expression and balances apoptosis and proliferation.

    Science.gov (United States)

    Simón, Rocío; Aparicio, Ricardo; Housden, Ben E; Bray, Sarah; Busturia, Ana

    2014-10-01

    A balance between cell proliferation and apoptosis is important for normal development and tissue homeostasis. Under stress conditions, the conserved tumor suppressor and transcription factor Dp53 induces apoptosis to contribute to the maintenance of homeostasis. However, in some cases Dp53-induced apoptosis results in the proliferation of surrounding non-apoptotic cells. To gain insight into the Dp53 function in the control of apoptosis and proliferation, we studied the interaction between the Drosophila Dp53 and Notch genes. We present evidence that simultaneous reduction of Dp53 and Notch function synergistically increases the wing phenotype of Notch heterozygous mutant flies. Further, we found that a Notch cis-regulatory element is responsive to loss and gain of Dp53 function and that over-expression of Dp53 up-regulates Notch mRNA and protein expression. These findings suggest not only that Dp53 and Notch act together to control wing development but also indicate that Dp53 transcriptionally regulates Notch expression. Moreover, using Notch  gain and loss of function mutations we examined the relevance of Dp53 and Notch interactions in the process of Dp53-apoptosis induced proliferation. Results show that proliferation induced by Dp53 over-expression is dependent on Notch, thus identifying Notch as a new player in Dp53-induced proliferation. Interestingly, we found that Dp53-induced Notch activation and proliferation occurs even under conditions where apoptosis was inhibited. Our findings highlight the conservation between flies and vertebrates of the Dp53 and Notch cross-talk and suggest that Dp53 has a dual role regulating cell death and proliferation gene networks to control the homeostatic balance between apoptosis and proliferation.

  12. Recent progress of Notch-1 signaling pathway in tumor research%Notch-1信号通路在肿瘤中的研究进展

    Institute of Scientific and Technical Information of China (English)

    张庆庆(综述); 陈伟; 张森林(审校)

    2014-01-01

    As one of members of the Notch gene family , Notch-1 signaling pathway plays an important role in the processing of cell proliferation , differentiation , survival and apoptosis .The abnormal expression of Notch-1 is closely related to tumorigenesis and de-velopment .In recent years , many studies have focused on the relationship between the Notch-1 signaling pathway and tumor .This arti-cle reviews the achievement of Notch-1 signaling pathway in recent tumor researches .%Notch-1是Notch基因家族的成员之一,Notch-1信号通路在细胞的增殖、分化、生存和凋亡中起着重要作用,其异常表达与肿瘤的发生、发展密切相关。近年来, Notch-1信号通路和肿瘤的关系研究颇多。文中就该信号通路在肿瘤中的研究进展作一综述。

  13. Hydraulic fracture during epithelial stretching

    Science.gov (United States)

    Casares, Laura; Vincent, Romaric; Zalvidea, Dobryna; Campillo, Noelia; Navajas, Daniel; Arroyo, Marino; Trepat, Xavier

    2015-03-01

    The origin of fracture in epithelial cell sheets subject to stretch is commonly attributed to excess tension in the cells’ cytoskeleton, in the plasma membrane, or in cell-cell contacts. Here, we demonstrate that for a variety of synthetic and physiological hydrogel substrates the formation of epithelial cracks is caused by tissue stretching independently of epithelial tension. We show that the origin of the cracks is hydraulic; they result from a transient pressure build-up in the substrate during stretch and compression manoeuvres. After pressure equilibration, cracks heal readily through actomyosin-dependent mechanisms. The observed phenomenology is captured by the theory of poroelasticity, which predicts the size and healing dynamics of epithelial cracks as a function of the stiffness, geometry and composition of the hydrogel substrate. Our findings demonstrate that epithelial integrity is determined in a tension-independent manner by the coupling between tissue stretching and matrix hydraulics.

  14. The hydraulic jump and ripples in liquid helium

    Energy Technology Data Exchange (ETDEWEB)

    Rolley, E. [Laboratoire de Physique Statistique de l' ENS, associe au CNRS et aux Universites Paris 6 et Paris 7, 24 rue Lhomond, 75005 Paris (France)]. E-mail: rolley@lps.ens.fr; Guthmann, C. [Laboratoire de Physique Statistique de l' ENS, associe au CNRS et aux Universites Paris 6 et Paris 7, 24 rue Lhomond, 75005 Paris (France); Pettersen, M.S. [Washington and Jefferson College, 60 S. Lincoln St., Washington, PA 15301 (United States)

    2007-05-01

    We have studied the characteristics of the circular hydraulic jump using liquid helium. Surprisingly, the radius of the jump does not change at the superfluid transition. We think that the flow is still dissipative below the lambda point because the velocity exceeds the critical one. The jump radius R{sub j} is compared with various models. In our parameter range, we find that the jump can be treated as a shock, and that capillary effects are important. Below the superfluid transition, we observed a standing capillary wave between the impact of the jet and the jump. Assuming that the superfluid flow can be described with an effective viscosity, we calculate the wave vector and thus obtain the value of the liquid thickness, which is in reasonable agreement with predictions. However, the spatial variation of the wave amplitude depends much more strongly on temperature than we calculate.

  15. Bio-based Hydraulic Fluids

    Science.gov (United States)

    2008-04-17

    currently formulated with vegetable oils (i.e., rapeseed , sun flower, corn, soybean, canola, coconut, etc.) and synthetic ester, such as polyol ester...2008 Vegetable Oil • Excellent lubrication • Nontoxic • Biodegradable • Derived from renewable resources such as rapeseed , sunflower, corn...Mineral Oil 100 SAE 15W-40 G Rapeseed 32 Commercial HF H Polyol ester 22 MIL-PRF-32073 Grade 2 I Canola - Cooking Oil *Hydraulic fluid 3717 April

  16. Fire Resistant Aircraft Hydraulic System.

    Science.gov (United States)

    1982-07-01

    and compounds based on new experimental elastomers as well as most commercially available elastomers were screened in seeking seals that were both...for hydraulic component testing. All of the available E6.5 stock was purchased for the screening tests. However, DuPont stated that other homologs of...with the lubricity and anti-wear additive olyvan A (molybdenum oxysulphide dithiocarbamate ) added in the quantity of less than one percent by weight

  17. The influence of the notches on the natural frequencies

    Directory of Open Access Journals (Sweden)

    Dekýš V.

    2007-10-01

    Full Text Available The simplification of the FEM model (the missing of a notch or a crack generally means the modification of the natural frequencies. An analysis of these changes is matter of this paper. The direct and semicircle notches were made on the testing specimens (by cut depth in the specimens and the naturals frequencies were measured and computed. The results are compared.In the paper is discussed the choice of the FEM element for FEM model and the comparison with experiment is made too.The influence of the crack on the natural frequencies is discussed in the case of specimen for high cycle fatigue test. The changes of the first three frequencies are compared for specimens with and without crack.

  18. Very compact quad band-notched UWB monopole antenna

    Science.gov (United States)

    Wu, Ling; Xia, Yingqing; Ye, Lei; Li, Lingzhi

    2016-10-01

    A very compact UWB antenna with four notched bands is proposed. The antenna consists of a rectangular radiating patch with a half circle at bottom, a tapered microstrip feed-line, and a semielliptical ground plane. With a pair of Lshaped slots, complementary co-directional SRR on the patch and a pair of L-shaped slots on the ground plane, four notched bands are created to prevent interference from WiMAX /WLAN/X-band. Experimental results show that the designed antenna, with compact size 20×30mm2, has an operating band(VSWR<2) from 2.7 to 20GHz,except four stop bands of 3.1 3.7GHz, 5.13 5.48GHz, 5.74 6.04GHz, 7.3 7.96GHz. And good radiation patterns within the operating band have been observed.

  19. Myositis ossificans within the intercondylar notch treated arthroscopically

    Energy Technology Data Exchange (ETDEWEB)

    Leung, Allen H.; Desai, Panna [Hospital for Joint Diseases/New York University, Department of Pathology, New York, NY (United States); Rybak, Leon D. [Hospital for Joint Diseases/New York University, Department of Radiology, New York, NY (United States); Rose, Donald J. [Hospital for Joint Diseases/New York University, Department of Orthopedic Surgery, New York, NY (United States)

    2010-09-15

    We present a case of intraarticular myositis ossificans in the right knee of a child. Myositis ossificans (MO), though relatively rare in childhood and even more uncommon within a joint, should be included in the differential diagnosis of an intra-articular mass when indicated by the typical clinical, radiographic, and histologic findings. An 11-year-old male presented with a history of trauma to his right knee. Four weeks after the initial injury, an MRI demonstrated evidence of an ACL rupture with a ''cystic mass'' within the intercondylar notch along the anterior surface of the torn ligament. At subsequent arthroscopy, the mass noted on MRI was removed. The histology was consistent with MO. The authors believe this to be the first case of MO in the intercondylar notch detected by MRI, treated by arthroscopy, and confirmed by histology. (orig.)

  20. Cooperation of Notch and Ras/MAPK signaling pathways in human breast carcinogenesis

    Directory of Open Access Journals (Sweden)

    Dey Devaveena

    2009-12-01

    Full Text Available Abstract Background Recent studies have implicated aberrant Notch signaling in breast cancers. Yet, relatively little is known about the pattern of expression of various components of the Notch pathway, or its mechanism of action. To better understand the role of the Notch pathway in breast cancer, we have undertaken a detailed expression analysis of various Notch receptors, their ligands, and downstream targets at different stages of breast cancer progression. Results We report here that there is a general increase in the expression levels of Notch 1, 2, 4, Jagged1, Jagged2, and Delta-like 4 proteins in breast cancers, with simultaneous upregulation of multiple Notch receptors and ligands in a given cancer tissue. While Notch3 and Delta-like1 were undetectable in normal tissues, moderate to high expression was detected in several cancers. We detected the presence of active, cleaved Notch1, along with downstream targets of the Notch pathway, Hes1/Hes5, in ~75% of breast cancers, clearly indicating that in a large proportion of breast cancers Notch signaling is aberrantly activated. Furthermore, we detected cleaved Notch1 and Hes1/5 in early precursors of breast cancers - hyperplasia and ductal carcinoma in situ - suggesting that aberrant Notch activation may be an early event in breast cancer progression. Mechanistically, while constitutively active Notch1 alone failed to transform immortalized breast cells, it synergized with the Ras/MAPK pathway to mediate transformation. This cooperation is reflected in vivo, as a subset of cleaved Notch positive tumors additionally expressed phopsho-Erk1/2 in the nuclei. Such cases exhibited high node positivity, suggesting that Notch-Ras cooperation may lead to poor prognosis. Conclusions High level expression of Notch receptors and ligands, and its increased activation in several breast cancers and early precursors, places Notch signaling as a key player in breast cancer pathogenesis. Its cooperation with

  1. V-Notched Bar Creep Life Prediction: GH3536 Ni-Based Superalloy Under Multiaxial Stress State

    Science.gov (United States)

    Zhang, D. X.; Wang, J. P.; Wen, Z. X.; Liu, D. S.; Yue, Z. F.

    2016-07-01

    In this study, creep experiments on smooth and circumferential V-type notched round bars were conducted in GH3536 Ni-based superalloy at 750 °C to identify notch strengthening effect in notched specimens. FE analysis was carried out, coupled with continuum damage mechanics (CDM), to analyze stress distribution and damage evolution under multiaxial stress state. The creep deformation of smooth specimens and the rupture life of both smooth and notched specimens showed good agreement between experimental results and FE analysis predictions; the creep rupture life for the notched specimen was successfully predicted via the "skeletal point" concept. Both creep damage analysis and the observed fracture morphology suggest that creep rupture started first at the root in the V-type notched specimens, and shifted to the region close to the notch root when the notch was relatively shallow compared to U-type notched specimens.

  2. Xanthohumol inhibits Notch signaling and induces apoptosis in hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Selvi Kunnimalaiyaan

    Full Text Available Despite improvement in therapeutic strategies, median survival in advanced hepatocellular carcinoma (HCC remains less than one year. Therefore, molecularly targeted compounds with less toxic profiles are needed. Xanthohumol (XN, a prenylated chalcone has been shown to have anti-proliferative effects in various cancers types in vitro. XN treatment in healthy mice and humans yielded favorable pharmacokinetics and bioavailability. Therefore, we determined to study the effects of XN and understand the mechanism of its action in HCC. The effects of XN on a panel of HCC cell lines were assessed for cell viability, colony forming ability, and cellular proliferation. Cell lysates were analyzed for pro-apoptotic (c-PARP and cleaved caspase-3 and anti-apoptotic markers (survivin, cyclin D1, and Mcl-1. XN concentrations of 5 μM and above significantly reduced the cell viability, colony forming ability and also confluency of all four HCC cell lines studied. Furthermore, growth suppression due to apoptosis was evidenced by increased expression of pro-apoptotic and reduced expression of anti-apoptotic proteins. Importantly, XN treatment inhibited the Notch signaling pathway as evidenced by the decrease in the expression of Notch1 and HES-1 proteins. Ectopic expression of Notch1 in HCC cells reverses the anti-proliferative effect of XN as evidenced by reduced growth suppression compared to control. Taken together these results suggested that XN mediated growth suppression is appeared to be mediated by the inhibition of the Notch signaling pathway. Therefore, our findings warrants further studies on XN as a potential agent for the treatment for HCC.

  3. Xanthohumol inhibits Notch signaling and induces apoptosis in hepatocellular carcinoma.

    Science.gov (United States)

    Kunnimalaiyaan, Selvi; Sokolowski, Kevin M; Balamurugan, Mariappan; Gamblin, T Clark; Kunnimalaiyaan, Muthusamy

    2015-01-01

    Despite improvement in therapeutic strategies, median survival in advanced hepatocellular carcinoma (HCC) remains less than one year. Therefore, molecularly targeted compounds with less toxic profiles are needed. Xanthohumol (XN), a prenylated chalcone has been shown to have anti-proliferative effects in various cancers types in vitro. XN treatment in healthy mice and humans yielded favorable pharmacokinetics and bioavailability. Therefore, we determined to study the effects of XN and understand the mechanism of its action in HCC. The effects of XN on a panel of HCC cell lines were assessed for cell viability, colony forming ability, and cellular proliferation. Cell lysates were analyzed for pro-apoptotic (c-PARP and cleaved caspase-3) and anti-apoptotic markers (survivin, cyclin D1, and Mcl-1). XN concentrations of 5 μM and above significantly reduced the cell viability, colony forming ability and also confluency of all four HCC cell lines studied. Furthermore, growth suppression due to apoptosis was evidenced by increased expression of pro-apoptotic and reduced expression of anti-apoptotic proteins. Importantly, XN treatment inhibited the Notch signaling pathway as evidenced by the decrease in the expression of Notch1 and HES-1 proteins. Ectopic expression of Notch1 in HCC cells reverses the anti-proliferative effect of XN as evidenced by reduced growth suppression compared to control. Taken together these results suggested that XN mediated growth suppression is appeared to be mediated by the inhibition of the Notch signaling pathway. Therefore, our findings warrants further studies on XN as a potential agent for the treatment for HCC.

  4. An evaluation of Top Notch fundamental A and B

    OpenAIRE

    Mahboobeh Tavakol; Sima Sayadian

    2013-01-01

    Adopting the appropriate textbook is a controversial task for second/foreign language teachers. In Iranian EFL situation where the teachers are not usually textbook providers but just consumers of other peoples material, there might be a need to evaluate the available EFL textbooks and investigate their contribution to general English courses. This paper aims at evaluating Top Notch fundamentals in terms of their impact on Iranian learners’ communicative and pragmatic competence. It is based...

  5. Delta-Notch Lateral Inhibition within the Organ of Corti

    Science.gov (United States)

    Summers, R.; Abdulla, T.; Luff, R.

    2013-09-01

    Lateral inhibition is described as an emergent property of the Delta-Notch signalling network. Two separate model representations of lateral inhibition are proposed for different purposes. One provides information about bioenergetics while the other has the capability to produce a physical representation. It is proposed that both can be used in further studies of the sensory pathways in the human connectome model of brain function.

  6. HOM Coupler Notch Filter Tuning for the European XFEL Cavities

    OpenAIRE

    Sulimov, Alexey

    2015-01-01

    The notch filter (NF) tuning prevents the extraction of fundamental mode (1.3 GHz) RF power through Higher Order Modes (HOM) couplers. The procedure of NF tuning was optimized at the beginning of serial European XFEL cavities production. It allows keeping the filter more stable against temperature and pressure changes during cavity cool down. Some statistics of NF condition during cavities and modules cold tests is presented.

  7. Characterization of slip lines in single edge notched tension specimens

    OpenAIRE

    Van Gerven, Filip; De Waele, Wim; Belato Rosado, Diego; Hertelé, Stijn

    2015-01-01

    The application of slip line analysis in weld failure assessment has not gained much attention to date. The presented research aims to predict slip line patterns taking into account the complex heterogeneous structure of the weld. A preliminary study based on Single Edge Notched Tension (SENT) test results sampling pure base material, i.e. not containing any welds is conducted to assess the impact of side grooves on slip line behaviour and to validate slip line theory and finite element analy...

  8. Role of Notch signaling pathway in gastric cancer pathogenesis

    OpenAIRE

    2013-01-01

    Notch signaling pathway is activated dynamically during evolution playing significant role in cell fate determination and differentiation. It has been known that alterations of this pathway may lead to human malignancies, including gastric cancer. Despite a decline in the overall incidence, this disease still remains an important global health problem. Therefore, a better understanding of the molecular alterations underlying gastric cancer may contribute to the development of rationally desig...

  9. Frequency Agile Microwave Photonic Notch Filter in a Photonic Chip

    Science.gov (United States)

    2016-10-21

    rejection, a wide frequency tuning, and flexible bandwidth reconfigurability, integrated in a compact photonic chip. 15.  SUBJECT TERMS Electro-optic...MWP) notch filter with a very narrow isolation bandwidth, an ultrahigh stopband rejection, a wide frequency tuning, and flexible bandwidth...prototype and the computer is done through USBs. The control software is written in LabVIEW and the screen -shot of the graphical user interface (GUI

  10. [The pulsed water jet for selective removal of bone cement during revision arthroplasty].

    Science.gov (United States)

    Honl, Matthias; Schwieger, Karsten; Carrero, Volker; Rentzsch, Reemt; Dierk, Oliver; Dries, Sebastian; Pude, Frank; Bluhm, Andrea; Hille, Ekkehard; Louis, Hartmut; Morlock, Michael

    2003-10-01

    Conventional tools used in prosthetic revision surgery have a limited range of action within the narrow cement mantle. Water jet cutting technology permits tiny and precisely controlled cuts, and may therefore be an alternative method of bone cement removal. Our study compares the cutting performance on bone cement (PMMA) and bone of a pulsed water jet and a continuous water jet. The aim of the study was to establish whether selective removal of PMMA is possible. 55 bone specimens (bovine femora) and 32 specimens of PMMA were cut with a continuous and a pulsed water jet at different pressures (40 MPa, 60 MPa) and pulse frequencies (0Hz, 50Hz, 250Hz). To ensure comparability of the results, the depths of cut were related to the hydraulic power of that part of the jet actually impinging on the material. While for PMMA the power-related depth of cut increased significantly with the pulse frequency, this did not apply to bone. The cuts produced in bone were sharp-edged. Since PMMA is more brittle than bone, the water jet caused cracks that enlarged further until particles of bone broke away. Although selective removal of PMMA without doing damage to the bone was not possible at the investigated settings of the jet parameters, the results do show that a pulsed water jet can cut bone cement much more effectively than bone. This is an important advantage over conventional non-selective tools for the removal of bone cement.

  11. B-jets and z + b-jets at CDF

    Energy Technology Data Exchange (ETDEWEB)

    Jeans, Daniel; /Rome U.

    2006-06-01

    The authors present CDF cross-section measurements for the inclusive production of b jets and the production of b jets in association with a Z{sup 0} boson. Both measurements are in reasonable agreement with NLO QCD predictions.

  12. Notch signaling: targeting cancer stem cells and epithelial-to-mesenchymal transition

    Directory of Open Access Journals (Sweden)

    Espinoza I

    2013-09-01

    Full Text Available Ingrid Espinoza,1,2 Radhika Pochampally,1,2 Fei Xing,1 Kounosuke Watabe,1,3 Lucio Miele1,4 1Cancer Institute, 2Department of Biochemistry, 3Department of Microbiology, 4Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, USA Abstract: Notch signaling is an evolutionarily conserved pathway involved in cell fate control during development, stem cell self-renewal, and postnatal tissue differentiation. Roles for Notch in carcinogenesis, the biology of cancer stem cells, tumor angiogenesis, and epithelial-to-mesenchymal transition (EMT have been reported. This review describes the role of Notch in the “stemness” program in cancer cells and in metastases, together with a brief update on the Notch inhibitors currently under investigation in oncology. These agents may be useful in targeting cancer stem cells and to reverse the EMT process. Keywords: Notch signaling, EMT, cancer stem cells, mesenchymal stem cells, metastases, Notch inhibitors

  13. A Notch-dependent molecular circuitry initiates pancreatic endocrine and ductal cell differentiation

    DEFF Research Database (Denmark)

    Shih, Hung Ping; Kopp, Janel L; Sandhu, Manbir

    2012-01-01

    In the pancreas, Notch signaling is thought to prevent cell differentiation, thereby maintaining progenitors in an undifferentiated state. Here, we show that Notch renders progenitors competent to differentiate into ductal and endocrine cells by inducing activators of cell differentiation. Notch...... signaling promotes the expression of Sox9, which cell-autonomously activates the pro-endocrine gene Ngn3. However, at high Notch activity endocrine differentiation is blocked, as Notch also induces expression of the Ngn3 repressor Hes1. At the transition from high to intermediate Notch activity, only Sox9......, but not Hes1, is maintained, thus de-repressing Ngn3 and initiating endocrine differentiation. In the absence of Sox9 activity, endocrine and ductal cells fail to differentiate, resulting in polycystic ducts devoid of primary cilia. Although Sox9 is required for Ngn3 induction, endocrine differentiation...

  14. A Notch-dependent molecular circuitry initiates pancreatic endocrine and ductal cell differentiation

    DEFF Research Database (Denmark)

    Shih, Hung Ping; Kopp, Janel L; Sandhu, Manbir

    2012-01-01

    In the pancreas, Notch signaling is thought to prevent cell differentiation, thereby maintaining progenitors in an undifferentiated state. Here, we show that Notch renders progenitors competent to differentiate into ductal and endocrine cells by inducing activators of cell differentiation. Notch...... signaling promotes the expression of Sox9, which cell-autonomously activates the pro-endocrine gene Ngn3. However, at high Notch activity endocrine differentiation is blocked, as Notch also induces expression of the Ngn3 repressor Hes1. At the transition from high to intermediate Notch activity, only Sox9......, but not Hes1, is maintained, thus de-repressing Ngn3 and initiating endocrine differentiation. In the absence of Sox9 activity, endocrine and ductal cells fail to differentiate, resulting in polycystic ducts devoid of primary cilia. Although Sox9 is required for Ngn3 induction, endocrine differentiation...

  15. THEORETICAL AND EXPERIMENTAL STUDIES ON FRACTURE PLANE CONTROL BLAST WITH NOTCHED BOREHOLES

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    The results of theoretical studies and field tests on fracture plane control blast with notched boreholes have been introduced. In these studies, the single symmetrical notched borehole was simplified to a pressurized hole with two symmetrical cracks under the state of plane strain. In analyzing the growth and termination of the notch, only quasi-static pressure was considered. In the mean time, the rock to be blasted was considered to be isotropic. Based on the principles of fracture mechanics, the stress components near the tip of the notch were calculated, and the criteria for growth and termination of the notch were established. The growth direction of the notch was also predicted on the basis of strain energy density factor. An approach for estimating the amount of explosive for each hole and the spacing of holes was suggested. Furthermore, field tests were conducted to check the results from the theoretical studies.

  16. Sub-microsecond beam notching at low energy

    Energy Technology Data Exchange (ETDEWEB)

    Moehs, D.P.; /Fermilab

    2005-09-01

    A technique for creating a burst of 100 ns notches (beam extinctions) in an H{sup -} beam at 454 kHz has been developed at {le} 20 keV utilizing a Magnetron ion source with a slit extraction system and a split extractor. Each half of the extractor is treated as part of a 50 ohm transmission line which can be pulsed at {+-} 700 volts creating a 1400 volt gradient across the extractor. A beam current reduction of better than 95% has been observed at the end of the Fermilab 400 MeV Linac. Notched multi-turn charge-exchange injection into the Booster, a 400 MeV to 8 GeV synchrotron, has been demonstrated with a charge reduction in the resulting beam gap of 83%. Presently, the trailing edge of the notch may be adversely affected by space charge resulting in a beam recovery with two different time constants. Efforts to minimize this effect are discussed.

  17. Laminar flow downregulates Notch activity to promote lymphatic sprouting.

    Science.gov (United States)

    Choi, Dongwon; Park, Eunkyung; Jung, Eunson; Seong, Young Jin; Yoo, Jaehyuk; Lee, Esak; Hong, Mingu; Lee, Sunju; Ishida, Hiroaki; Burford, James; Peti-Peterdi, Janos; Adams, Ralf H; Srikanth, Sonal; Gwack, Yousang; Chen, Christopher S; Vogel, Hans J; Koh, Chester J; Wong, Alex K; Hong, Young-Kwon

    2017-04-03

    The major function of the lymphatic system is to drain interstitial fluid from tissue. Functional drainage causes increased fluid flow that triggers lymphatic expansion, which is conceptually similar to hypoxia-triggered angiogenesis. Here, we have identified a mechanotransduction pathway that translates laminar flow-induced shear stress to activation of lymphatic sprouting. While low-rate laminar flow commonly induces the classic shear stress responses in blood endothelial cells and lymphatic endothelial cells (LECs), only LECs display reduced Notch activity and increased sprouting capacity. In response to flow, the plasma membrane calcium channel ORAI1 mediates calcium influx in LECs and activates calmodulin to facilitate a physical interaction between Krüppel-like factor 2 (KLF2), the major regulator of shear responses, and PROX1, the master regulator of lymphatic development. The PROX1/KLF2 complex upregulates the expression of DTX1 and DTX3L. DTX1 and DTX3L, functioning as a heterodimeric Notch E3 ligase, concertedly downregulate NOTCH1 activity and enhance lymphatic sprouting. Notably, overexpression of the calcium reporter GCaMP3 unexpectedly inhibited lymphatic sprouting, presumably by disturbing calcium signaling. Endothelial-specific knockouts of Orai1 and Klf2 also markedly impaired lymphatic sprouting. Moreover, Dtx3l loss of function led to defective lymphatic sprouting, while Dtx3l gain of function rescued impaired sprouting in Orai1 KO embryos. Together, the data reveal a molecular mechanism underlying laminar flow-induced lymphatic sprouting.

  18. Ruptured Arteriovenous Malformation Presenting with Kernohan’s Notch

    Directory of Open Access Journals (Sweden)

    Christopher F. Dibble

    2015-01-01

    Full Text Available AVMs are congenital lesions that predispose patients to intracranial hemorrhage and resultant neurological deficits. These deficits are often focal and due to the presence of local neurologic disruption from hemorrhage in the contralateral cerebral hemisphere. We present a rare case of a patient with ipsilateral neurological deficits due to Kernohan’s Notch phenomenon resulting from hemorrhage from an AVM. A 31-year-old woman with seizures underwent MR and angiographic imaging which confirmed an unruptured left parietal AVM. The patient declined treatment and presented with obtundation 4 years later. Imaging revealed an acute left parietal ICH and SDH with significant mass effect. The patient underwent emergent hemicraniectomy and hematoma evacuation. Postoperatively, she made significant improvement and was following commands contralaterally with ipsilateral hemiplegia. MR imaging revealed right Kernohan’s Notch. The patient had significant rehabilitation with neurological improvement. She eventually underwent elective embolization followed by subsequent surgical resection and bone replacement. Three years from the initial hemorrhage, the patient had only mild left-sided weakness and ambulates without assistance. A false localizing sign, Kernohan’s Notch phenomenon, should be considered in the setting of AVM hemorrhage with paradoxical motor impairment and can be identified through MRI.

  19. Magnetic domain wall motion in notch patterned permalloy nanowire devices

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ting-Chieh; Kuo, Cheng-Yi; Mishra, Amit K.; Das, Bipul; Wu, Jong-Ching, E-mail: phjcwu@cc.ncue.edu.tw

    2015-11-01

    We report a study of magnetization reversal process of notch-patterned permalloy (Py) nanowires (NWs) by using an in-situ magnetic force microscopy (MFM). Three neighboring straight NWs and an individual straight NW with discs connected to the wires ends are fabricated by standard electron beam lithography through a lift-off technique. MFM images are taken in the presence of an in-plane magnetic field applied along the wires length. As a result, the nucleation, pinning and depinning of domain walls (DWs) along the NW are observed. The artificial constraints (notch) in such symmetrical geometry of NWs indeed serve as pinning sites to pin the DWs. The nature of magnetization reversal, pinning field and depinning field for the DWs that are observed in these permalloy NWs, indicate the key roles of notch depth, the terminal connection structure of NW end and the inter-wire interaction among the NWs. The in-situ MFM measurements are examined with the micromagnetic simulations. Consequently, good agreements are obtained for the DW structures and the effect of DWs pining/depinning, however a dissimilarity in experimental and simulation observations for the direction of propagation of DWs in NWs needs further investigation.

  20. Hydraulic Redistribution: A Modeling Perspective

    Science.gov (United States)

    Daly, E.; Verma, P.; Loheide, S. P., III

    2014-12-01

    Roots play a key role in the soil water balance. They extract and transport water for transpiration, which usually represents the most important soil water loss in vegetated areas, and can redistribute soil water, thereby increasing transpiration rates and enhancing root nutrient uptake. We present here a two-dimensional model capable of describing two key aspects of root water uptake: root water compensation and hydraulic redistribution. Root water compensation is the ability of root systems to respond to the reduction of water uptake from areas of the soil with low soil water potential by increasing the water uptake from the roots in soil parts with higher water potential. Hydraulic redistribution is a passive transfer of water through the root system from areas of the soil with greater water potential to areas with lower water potential. Both mechanisms are driven by gradients of water potential in the soil and the roots. The inclusion of root water compensation and hydraulic redistribution in models can be achieved by describing root water uptake as a function of the difference in water potential between soil and root xylem. We use a model comprising the Richards equation for the water flow in variably saturated soils and the Darcy's equation for the water flow in the xylem. The two equations are coupled via a sink term, which is assumed to be proportional to the difference between soil and xylem water potentials. The model is applied in two case studies to describe vertical and horizontal hydraulic redistribution and the interaction between vegetation with different root depths. In the case of horizontal redistribution, the model is used to reproduce the fluxes of water across the root system of a tree subjected to uneven irrigation. This example can be extended to situations when only part of the root system has access to water, such as vegetation near creeks, trees at the edge of forests, and street trees in urban areas. The second case is inspired by recent

  1. Relativistic AGN jets I. The delicate interplay between jet structure, cocoon morphology and jet-head propagation

    NARCIS (Netherlands)

    Walg, S.; Achterberg, A.; Markoff, S.; Keppens, R.; Meliani, Z.

    2013-01-01

    Astrophysical jets reveal strong signs of radial structure. They suggest that the inner region of the jet, the jet spine, consists of a low-density, fast-moving gas, while the outer region of the jet consists of a more dense and slower moving gas, called the jet sheath. Moreover, if jets carry angul

  2. Notch signaling induces rapid degradation of achaete-scute homolog 1.

    Science.gov (United States)

    Sriuranpong, Virote; Borges, Michael W; Strock, Christopher L; Nakakura, Eric K; Watkins, D Neil; Blaumueller, Christine M; Nelkin, Barry D; Ball, Douglas W

    2002-05-01

    In neural development, Notch signaling plays a key role in restricting neuronal differentiation, promoting the maintenance of progenitor cells. Classically, Notch signaling causes transactivation of Hairy-enhancer of Split (HES) genes which leads to transcriptional repression of neural determination and differentiation genes. We now report that in addition to its known transcriptional mechanism, Notch signaling also leads to rapid degradation of the basic helix-loop-helix (bHLH) transcription factor human achaete-scute homolog 1 (hASH1). Using recombinant adenoviruses expressing active Notch1 in small-cell lung cancer cells, we showed that the initial appearance of Notch1 coincided with the loss of hASH1 protein, preceding the full decay of hASH1 mRNA. Overexpression of HES1 alone was capable of down-regulating hASH1 mRNA but could not replicate the acute reduction of hASH1 protein induced by Notch1. When adenoviral hASH1 was coinfected with Notch1, we still observed a dramatic and abrupt loss of the exogenous hASH1 protein, despite high levels of ongoing hASH1 RNA expression. Notch1 treatment decreased the apparent half-life of the adenoviral hASH1 protein and increased the fraction of hASH1 which was polyubiquitinylated. The proteasome inhibitor MG132 reversed the Notch1-induced degradation. The Notch RAM domain was dispensable but a lack of the OPA and PEST domains inactivated this Notch1 action. Overexpression of the hASH1-dimerizing partner E12 could protect hASH1 from degradation. This novel function of activated Notch to rapidly degrade a class II bHLH protein may prove to be important in many contexts in development and in cancer.

  3. Double-notch-shaped microdisk resonator devices with gapless coupling on a silicon chip Invited Paper

    Institute of Scientific and Technical Information of China (English)

    Xianshu Luo; Andrew W. Poon

    2009-01-01

    We propose novel double-notch-shaped microdisk resonator-based devices with gapless waveguide-to- microdisk and inter-cavity coupling via the two notches of the microdisk. Both finite-difference time- domain simulations and experimental demonstrations reveal the high-quality-factor multimode resonances in such microdisks. Using such double-notch microdisk resonators, we experimentally demonstrate the many-element linearly cascaded-microdisk resonator devices with up to 50 elements on a silicon chip.

  4. Integrated Regulation of Toll-like Receptor Responses by Notch and Interferon-γ Pathways

    OpenAIRE

    2008-01-01

    Toll-like receptor (TLR) responses are regulated to avoid toxicity and achieve coordinated responses appropriate for the cell environment. We found that Notch and TLR pathways cooperated to activate canonical Notch target genes, including transcriptional repressors Hes1 and Hey1, and to increase production of canonical TLR-induced cytokines TNF, IL-6 and IL-12. Cooperation by these pathways to increase target gene expression was mediated the Notch pathway component and transcription factor RB...

  5. Finite element analysis of the stress-concentrating effect of fraenal notches in complete dentures.

    Science.gov (United States)

    Rees, J S; Huggett, R; Harrison, A

    1990-01-01

    Based on clinical experience and empiricism, it was postulated that fraenal notches and midline diastemas lead to fracture of complete dentures. This study used finite element stress analysis to investigate the stress-concentrating effect of a fraenal notch with and without a midline diastema. It was found that a large fraenal notch resulted in high stress levels and that these stresses were augmented more by a narrow median diastema than its wider counterpart.

  6. Notch pathway promotes ovarian cancer growth and migration via CXCR4/SDF1α chemokine system.

    Science.gov (United States)

    Chiaramonte, R; Colombo, M; Bulfamante, G; Falleni, M; Tosi, D; Garavelli, S; De Simone, D; Vigolo, E; Todoerti, K; Neri, A; Platonova, N

    2015-09-01

    Ovarian cancer is the most deadly gynecological malignancy. Understanding the molecular pathogenesis of ovarian cancer is critical to provide new targeted therapeutic strategies. Recent evidence supports a role for Notch in ovarian cancer progression and associates its dysregulation to poor overall survival. Similarly, CXCR4/SDF1α signalling correlates with ovarian cancer progression and metastasis. Recent findings indicate that Notch promotes CXCR4/SDF1α signalling and its effect on cell growth and migration; nonetheless, up to now, the association between Notch and CXCR4/SDFα in ovarian cancer has not been reported. Thereby, the aim of this study was to investigate if Notch and CXCR4/SDF1α cooperate in determining ovarian cancer growth, survival and migration. To address this issue, Notch signalling was inhibited by using γ-secretase inhibitors, or upregulated by forcing of Notch1 expression in ovarian cancer cell lines. Our results indicated that Notch activity influenced tumour cell growth and survival and positively regulated CXCR4 and SDF1α expression. CXCR4/SDF1α signalling mediated the effect of Notch pathway on ovarian cancer cell growth and SDF1α-driven migration. Additionally, for the first time, we demonstrated that Notch signalling activation can be detected in ovarian cancer specimens by immunohistochemistry analysis of the Notch transcriptional target, HES6 and is positively correlated with high expression levels of CXCR4 and SDF1α. Our results demonstrate that Notch affects ovarian cancer cell biology through the modulation of CXCR4/SDF1α signalling and suggest that Notch inhibition may be a rationale therapeutic approach to hamper ovarian cancer progression mediated by the CXCR4/SDF1α axis.

  7. Active form Notch4 promotes the proliferation and differentiation of 3T3-L1 preadipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Lai, Peng-Yeh [Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chiayi 621, Taiwan, ROC (China); Tsai, Chong-Bin [Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chiayi 621, Taiwan, ROC (China); Department of Ophthalmology, Chiayi Christian Hospital, Chiayi 600, Taiwan, ROC (China); Tseng, Min-Jen, E-mail: biomjt@ccu.edu.tw [Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chiayi 621, Taiwan, ROC (China)

    2013-01-18

    Highlights: ► Notch4IC modulates the ERK pathway and cell cycle to promote 3T3-L1 proliferation. ► Notch4IC facilitates 3T3-L1 differentiation by up-regulating proadipogenic genes. ► Notch4IC promotes proliferation during the early stage of 3T3-L1 adipogenesis. ► Notch4IC enhances differentiation during subsequent stages of 3T3-L1 adipogenesis. -- Abstract: Adipose tissue is composed of adipocytes, which differentiate from precursor cells in a process called adipogenesis. Many signal molecules are involved in the transcriptional control of adipogenesis, including the Notch pathway. Previous adipogenic studies of Notch have focused on Notch1 and HES1; however, the role of other Notch receptors in adipogenesis remains unclear. Q-RT-PCR analyses showed that the augmentation of Notch4 expression during the differentiation of 3T3-L1 preadipocytes was comparable to that of Notch1. To elucidate the role of Notch4 in adipogenesis, the human active form Notch4 (N4IC) was transiently transfected into 3T3-L1 cells. The expression of HES1, Hey1, C/EBPδ and PPARγ was up-regulated, and the expression of Pref-1, an adipogenic inhibitor, was down-regulated. To further characterize the effect of N4IC in adipogenesis, stable cells expressing human N4IC were established. The expression of N4IC promoted proliferation and enhanced differentiation of 3T3-L1 cells compared with those of control cells. These data suggest that N4IC promoted proliferation through modulating the ERK pathway and the cell cycle during the early stage of 3T3-L1 adipogenesis and facilitated differentiation through up-regulating adipogenic genes such as C/EBPα, PPARγ, aP2, LPL and HSL during the middle and late stages of 3T3-L1 adipogenesis.

  8. Angiotensin II contributes to renal fibrosis independently of Notch pathway activation.

    Directory of Open Access Journals (Sweden)

    Carolina Lavoz

    Full Text Available Recent studies have described that the Notch signaling pathway is activated in a wide range of renal diseases. Angiotensin II (AngII plays a key role in the progression of kidney diseases. AngII contributes to renal fibrosis by upregulation of profibrotic factors, induction of epithelial mesenchymal transition and accumulation of extracellular matrix proteins. In cultured human tubular epithelial cells the Notch activation by transforming growth factor-β1 (TGF-β1 has been involved in epithelial mesenchymal transition. AngII mimics many profibrotic actions of TGF-β1. For these reasons, our aim was to investigate whether AngII could regulate the Notch/Jagged system in the kidney, and its potential role in AngII-induced responses. In cultured human tubular epithelial cells, TGF-β1, but not AngII, increased the Notch pathway-related gene expression, Jagged-1 synthesis, and caused nuclear translocation of the activated Notch. In podocytes and renal fibroblasts, AngII did not modulate the Notch pathway. In tubular epithelial cells, pharmacological Notch inhibition did not modify AngII-induced changes in epithelial mesenchymal markers, profibrotic factors and extracellular matrix proteins. Systemic infusion of AngII into rats for 2 weeks caused tubulointerstitial fibrosis, but did not upregulate renal expression of activated Notch-1 or Jagged-1, as observed in spontaneously hypertensive rats. Moreover, the Notch/Jagged system was not modulated by AngII type I receptor blockade in the model of unilateral ureteral obstruction in mice. These data clearly indicate that AngII does not regulate the Notch/Jagged signaling system in the kidney, in vivo and in vitro. Our findings showing that the Notch pathway is not involved in AngII-induced fibrosis could provide important information to understand the complex role of Notch system in the regulation of renal regeneration vs damage progression.

  9. Angiotensin II contributes to renal fibrosis independently of Notch pathway activation.

    Science.gov (United States)

    Lavoz, Carolina; Rodrigues-Diez, Raquel; Benito-Martin, Alberto; Rayego-Mateos, Sandra; Rodrigues-Diez, Raúl R; Alique, Matilde; Ortiz, Alberto; Mezzano, Sergio; Egido, Jesús; Ruiz-Ortega, Marta

    2012-01-01

    Recent studies have described that the Notch signaling pathway is activated in a wide range of renal diseases. Angiotensin II (AngII) plays a key role in the progression of kidney diseases. AngII contributes to renal fibrosis by upregulation of profibrotic factors, induction of epithelial mesenchymal transition and accumulation of extracellular matrix proteins. In cultured human tubular epithelial cells the Notch activation by transforming growth factor-β1 (TGF-β1) has been involved in epithelial mesenchymal transition. AngII mimics many profibrotic actions of TGF-β1. For these reasons, our aim was to investigate whether AngII could regulate the Notch/Jagged system in the kidney, and its potential role in AngII-induced responses. In cultured human tubular epithelial cells, TGF-β1, but not AngII, increased the Notch pathway-related gene expression, Jagged-1 synthesis, and caused nuclear translocation of the activated Notch. In podocytes and renal fibroblasts, AngII did not modulate the Notch pathway. In tubular epithelial cells, pharmacological Notch inhibition did not modify AngII-induced changes in epithelial mesenchymal markers, profibrotic factors and extracellular matrix proteins. Systemic infusion of AngII into rats for 2 weeks caused tubulointerstitial fibrosis, but did not upregulate renal expression of activated Notch-1 or Jagged-1, as observed in spontaneously hypertensive rats. Moreover, the Notch/Jagged system was not modulated by AngII type I receptor blockade in the model of unilateral ureteral obstruction in mice. These data clearly indicate that AngII does not regulate the Notch/Jagged signaling system in the kidney, in vivo and in vitro. Our findings showing that the Notch pathway is not involved in AngII-induced fibrosis could provide important information to understand the complex role of Notch system in the regulation of renal regeneration vs damage progression.

  10. Experience with the Notch Stress Approach for Fatigue Assessment of Welded Joints

    DEFF Research Database (Denmark)

    Pedersen, Mikkel Melters; Mouritsen, Ole Ø.; Hansen, Michael Rygaard

    2010-01-01

    In this paper, fatigue assessment using the notch stress approach is discussed based on re-analysis of many fatigue test results and experience from practical application. Three topics are treated; evaluation of the fatigue strength for as-welded details (FAT225) in the notch stress system......, problems regarding assessment of mild-SCF details and a novel proposal for extension of the notch stress approach for use with post-weld treated details....

  11. Immunolocalization of notch signaling protein molecules in a maxillary chondrosarcoma and its recurrent tumor

    Directory of Open Access Journals (Sweden)

    Siar CH

    2010-10-01

    Full Text Available Abstract Background Notch receptors are critical determinants of cell fate in a variety of organisms. Notch signaling is involved in the chondrogenic specification of neural crest cells. Aberrant Notch activity has been implicated in numerous human diseases including cancers; however its role in chondrogenic tumors has not been clarified. Method Tissue samples from a case of primary chondrosarcoma of the maxilla and its recurrent tumor were examined immunohistochemically for Notch1-4 and their ligands (Jagged1, Jagged2 and Delta1 expression. Results Both primary and recurrent tumors were histopathologically diagnosed as conventional hyaline chondrosarcoma (WHO Grade I. Hypercellular tumor areas strongly expressed Notch3 and Jagged1 in spindle and pleomorphic cells suggesting up-regulation of these protein molecules at sites of tumor proliferation. Expression patterns were distinct with some overlap. Differentiated malignant and atypical chondrocytes demonstrated variable expression levels of Jagged1, and weak to absent staining for Notch1, 4 and Delta1. Protein immunolocalization was largely membranous and cytoplasmic, sometimes outlining the lacunae of malignant chondrocytes. Hyaline cartilage demonstrated a diffuse or granular precipitation of Jagged1 suggesting presence of soluble Jagged1 activity at sites of abnormal chondrogenesis. No immunoreactivity for the other Notch members was observed. Calcified cartilage was consistently Notch-negative indicating down-regulation of Notch with cartilage maturation. Stromal components namely endothelial cells and fibroblasts variably expressed Notch1, 3 and Jagged1 but were mildly or non-reactive for the other members. Conclusions Results indicate that Notch signaling pathway may participate in cellular differentiation and proliferation in chondrosarcoma. Findings implicate Notch3 and Jagged1 as key molecules that influence the differentiation and maturation of cells of chondrogenic lineage.

  12. Inhibition of Notch1 increases paclitaxel sensitivity to human breast cancer

    Institute of Scientific and Technical Information of China (English)

    Zhao Li; Ma Yongjie; Gu Feng; Fu Li

    2014-01-01

    Background Paclitaxel (PAC) is the first-line chemotherapy drug for most breast cancer patients,but clinical studies showed that some breast cancer patients were insensitive to PAC,which led to chemotherapy failure.It was reported that Notch1 signaling participated in drug resistance of breast cancer.Here,we show whether Notch1 expression is related to PAC sensitivity of breast cancer.Methods We employed Notch1 siRNA and Notch1 inhibitor,N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butylester (DAPT),to down regulate Notch1 expression in human breast cancer cells MDA-MB-231,and detected the inhibition effect by Western blotting and reverse trans cription-polymerase chain reaction,respectively.After 24 hours exposure to different concentration of PAC (0,1,5,10,15,20,and 25 μg/ml),the viability of the control group and experimental group cells was tested by MTT.We also examined the expression of Notch1 in PAC sensitive and nonsensitive breast cancer patients,respectively by immunohistochemistry (IHC).The PAC sensitivity of breast cancer patients were identified by collagen gel droplet embedded culture-drug sensitivity test (CD-DST).Results Down regulation of Notch1 expression by Notch1siRNA interference or Notch1 inhibitor increased the PAC sensitivity in MDA-MB-231 cells (P <0.05).Also,the expression of Notch1 in PAC sensitive patients was much lower than that of PAC non-sensitive patients (P <0.01).Conclusion Notch1 expression has an effect on PAC sensitivity in breast cancer patients,and the inhibition of Notch1 increases paclitaxel sensitivity to human breast cancer.

  13. Regulation of breast cancer stem cell activity by signaling through the Notch4 receptor

    OpenAIRE

    Harrison, Hannah; Farnie, Gillian; Howell, Sacha J.; Rock, Rebecca E; Stylianou, Spyros; Brennan, Keith R.; Bundred, Nigel J; Clarke, Robert B.

    2010-01-01

    Notch receptor signaling pathways play an important role not only in normal breast development but also in breast cancer development and progression. We assessed the role of Notch receptors in stem cell activity in breast cancer cell lines and nine primary human tumor samples. Stem cells were enriched by selection of anoikis-resistant cells or cells expressing the membrane phenotype ESA+/CD44+/CD24low. Using these breast cancer stem cell populations, we compared the activation status of Notch...

  14. Notch1-Snail1-E-cadherin pathway in metastatic hepatocellular carcinoma.

    Science.gov (United States)

    Wang, Xiao Qi; Zhang, Wu; Lui, Eric L H; Zhu, Yongqiang; Lu, Ping; Yu, Xiaoming; Sun, Jisan; Yang, Sitian; Poon, Ronnie T P; Fan, Sheung Tat

    2012-08-01

    Notch signaling, a critical pathway for tissue development, also contributes to tumorigenesis in many cancers, but its pathological function in liver cancer is not well defined. In our study, Notch1 expression and its clinicopathological parameters were evaluated in 82 human hepatocellular carcinoma (HCC) patients. Plasmid-based siNotch1 shRNA was transiently or stably transfected into metastatic HCC cells and subsequently evaluated for the effects on orthotopic liver tumor metastasis in a mouse model as well as the effects on downstream pathways. Aberrant high expression of Notch1 was significantly associated with metastatic disease parameters in HCC patients, such as tumor-node-metastasis Stages III-IV and tumor venous invasion. Knocking-down Notch1 reduced cell motility in vitro and orthotopic tumor metastasis from the liver to the lung in vivo in a mouse model. In metastatic HCC cells, abnormal expression of Notch1 was associated with increased expression of Snail1 and repressed expression of E-cadherin; the Notch1-Snail1-E-cadherin association can also be found in HCC patient tumors. Inhibition of Notch1 by shRNA abolished Snail1 expression, which further resulted in the re-establishment of repressed E-cadherin in metastatic HCC cells. Thus, abnormal Notch1 expression was strongly associated with HCC metastatic disease, which might be mediated through the Notch1-Snail1-E-cadherin pathway. Knock-down of Notch1 reversed HCC tumor metastasis in a mouse model. Therefore, these data suggest that effective targeting of Notch signaling might also inhibit tumor metastasis.

  15. The roles of Notch1 expression in the migration of intrahepatic cholangiocarcinoma

    OpenAIRE

    Zhou, Qi; Wang, Yafeng; Peng, Baogang; Liang, Lijian; Li, Jiaping

    2013-01-01

    Background Notch signaling, a critical pathway for tissue development, contributes to tumorigenesis in many tissues; however, the roles of Notch signaling in Intrahepatic Cholangiocarcinoma (ICC) remains unclear. In this study, we evaluated the expression and effects of Notch1 on cell migration in ICC. Methods Multiple cellular and molecular approaches were performed including gene transfection, siRNA transfection, RT-PCR, Western blotting, Rac activation assays and immunofluorescence. Result...

  16. Therapeutic approaches to modulating Notch signaling: Current challenges and future prospects

    OpenAIRE

    2012-01-01

    Dysregulated Notch signaling has been implicated in numerous human diseases, including a broad spectrum of cancers. Mutations in Notch1 are prevalent in T-cell acute lymphoblastic leukemia, and abnormal expression of different human Notch receptors contributes to B-cell tumors as well as cancers of the breast, lung, pancreas, skin, prostate, colon, brain and other tissues. Several γ-secretase inhibitors, small chemical compounds that were initially developed to inhibit the activity of the γ-s...

  17. Pharmacologic inhibition of Notch signaling suppresses food antigen-induced mucosal mast cell hyperplasia.

    Science.gov (United States)

    Honjo, Asuka; Nakano, Nobuhiro; Yamazaki, Susumu; Hara, Mutsuko; Uchida, Koichiro; Kitaura, Jiro; Nishiyama, Chiharu; Yagita, Hideo; Ohtsuka, Yoshikazu; Ogawa, Hideoki; Okumura, Ko; Shimizu, Toshiaki

    2017-03-01

    Mucosal mast cells (MMCs) play a central role in the development of symptoms associated with IgE-mediated food allergy. Recently, Notch2-mediated signaling was shown to be involved in proper MMC distribution in the intestinal tract. This study aimed to clarify the mechanism by which Notch signaling regulates MMC distribution in the intestinal mucosa. Furthermore, pharmacologic inhibition of Notch signaling was evaluated as a treatment for symptoms associated with experimental food allergy. Bone marrow-derived mast cells generated from mice were cultured with Notch ligands, and then expression of genes associated with MMCs was measured in the cells. In addition, the effect of an inhibitor of Notch signaling on food antigen-induced allergic reactions was examined in a mouse model of food allergy. Notch signaling induced MMC differentiation through upregulation of expression of genes characteristic of MMCs in the presence of IL-3. Some lamina propria cells isolated from the mouse small intestine expressed Notch ligands and were able to upregulate MMC markers in bone marrow-derived mast cells through Notch signaling. In a mouse model of food allergy, administration of a Notch signaling inhibitor led to suppression of food antigen-induced hyperplasia of intestinal MMCs, resulting in alleviation of allergic diarrhea and systemic anaphylaxis. Notch signaling contributes to differentiation and accumulation of MMCs in the intestinal mucosa. Thus inhibition of Notch signaling alleviates symptoms associated with experimental food allergy. These results raise the possibility that Notch signaling in mast cells is a novel target for therapy in patients with food allergy. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  18. Jet Substructure by Accident

    CERN Document Server

    Cohen, Timothy; Lisanti, Mariangela; Lou, Hou Keong

    2012-01-01

    We propose a new search strategy for high-multiplicity hadronic final states. When new particles are produced at threshold, the distribution of their decay products is approximately isotropic. If there are many partons in the final state, it is likely that several will be clustered into the same large-radius jet. The resulting jet exhibits substructure, even though the parent states are not boosted. This "accidental" substructure is a powerful discriminant against background because it is more pronounced for high-multiplicity signals than for QCD multijets. We demonstrate how to take advantage of accidental substructure to reduce backgrounds without relying on the presence of missing energy. As an example, we present the expected limits for several R-parity violating gluino decay topologies. This approach allows for the determination of QCD backgrounds using data-driven methods, which is crucial for the feasibility of any search that targets signatures with many jets and suppressed missing energy.

  19. Renewable jet fuel.

    Science.gov (United States)

    Kallio, Pauli; Pásztor, András; Akhtar, M Kalim; Jones, Patrik R

    2014-04-01

    Novel strategies for sustainable replacement of finite fossil fuels are intensely pursued in fundamental research, applied science and industry. In the case of jet fuels used in gas-turbine engine aircrafts, the production and use of synthetic bio-derived kerosenes are advancing rapidly. Microbial biotechnology could potentially also be used to complement the renewable production of jet fuel, as demonstrated by the production of bioethanol and biodiesel for piston engine vehicles. Engineered microbial biosynthesis of medium chain length alkanes, which constitute the major fraction of petroleum-based jet fuels, was recently demonstrated. Although efficiencies currently are far from that needed for commercial application, this discovery has spurred research towards future production platforms using both fermentative and direct photobiological routes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Multichannel discharge between jet electrolyte cathode and jet electrolyte anode

    NARCIS (Netherlands)

    Shakirova, E. F.; Gaitsin, Al. F.; Son, E. E.

    2011-01-01

    We present the results of an experimental study of multichannel discharge between a jet electrolyte cathode and jet electrolyte anode within a wide range of parameters. We pioneer the reveal of the burning particularities and characteristics of multichannel discharge with jet electrolyte and droplet