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Sample records for corroded hemispherical notches

  1. Experimental Evaluation of Fatigue Crack Initiation from Corroded Hemispherical Notches in Aerospace Structural Materials

    Science.gov (United States)

    Garcia, Daniel B.; Forman, Royce; Shindo, David

    2010-01-01

    A test program was developed and executed to evaluate the influence of corroded hemispherical notches on the fatigue crack initiation and propagation in aluminum 7075-T7351, 4340 steel, and D6AC steel. Surface enhancements such as shot peening and laser shock peening were also incorporated as part of the test effort with the intent of improving fatigue performance. In addition to the testing, fracture mechanics and endurance limit based analysis methods were evaluated to characterize the results with the objective of challenging typical assumptions used in modeling fatigue cracks from corrosion pits. The results specifically demonstrate that the aluminum and steel alloys behave differently with respect to fatigue crack initiation from hemispherical corrosion pits. The aluminum test results were bounded by the fracture mechanics and endurance limit models while exhibiting a general insensitivity to the residual stress field generated by shot peening. The steel specimens were better characterized by the endurance limit fatigue properties and did exhibit sensitivities to residual stresses from the shot peening and laser shock peening

  2. Ultrasonic Fatigue Endurance of Aluminum Alloy AISI 6061-T6 on Pre-corroded and Non-corroded Specimens

    Science.gov (United States)

    Domínguez Almaraz, Gonzalo M.; Dueñas Aburto, Antonio; Correa Gómez, Erasmo

    2014-01-01

    Ultrasonic fatigue tests are carried out on aluminum alloy 6061-T6 in order to analyze the fatigue endurance behavior under artificial pre-corrosion attack by hydrochloric acid for the pH concentrations of 0.47 and 0.80. The pre-corrosion attack is used to simulate the long-time environmental effect and the corresponding decay of fatigue life in regard to non-corroded specimens. Experimental results show that ultrasonic fatigue endurance under these two degrees of pre-corrosion attack decreases dramatically. Furthermore, it is observed that crack initiation is frequently associated with one or several pre-corrosion pitting holes at the specimen surface. Pitting holes are assumed to be semi-hemispherical and the stress concentration factors are evaluated taking into account the size and proximity of two crack initiation pitting holes. The crack growth rates are obtained for the pre-corroded specimens and compared to the non-corroded specimen. Finally, conclusions are listed concerning ultrasonic fatigue endurance of testing specimens, together with the fracture surfaces, crack paths, and crack growth rates.

  3. Plastic collapse load of corroded steel plates

    Indian Academy of Sciences (India)

    Rahbar Ranji Ahmad

    2012-06-01

    Corrosion is one of the detrimental phenomena which reduces strength of structures. It is common practice to assume a uniform thickness reduction for general corrosion. Since the actual corroded plate has rough surfaces, to estimate the remaining strength of corroded structures, typically a much higher level of accuracy is required. The main aim of present work is to study plastic collapse load of corroded steel plates with irregular surfaces under tension. Non-linear finite element method by using computer code ANSYS was employed to determine plastic collapse load. By comparing the results with uniform thickness assumption, a reduction factor was proposed. It is found that by uniform thickness assumption, plastic collapse load of corroded plates are overestimated.

  4. Elastic buckling strength of corroded steel plates

    Indian Academy of Sciences (India)

    Ahmad Rahbar-Ranji

    2013-02-01

    Corrosion makes structures more vulnerable to buckling and yielding failures. It is common practice to assume a uniform thickness reduction for general corrosion. To estimate the remaining strength of corroded structures, typically a much higher level of accuracy is required, since the actual corroded structures have irregular surfaces. Elastic buckling of simply supported rectangular corroded plates are studied with one- and both-sided irregular surfaces. Eigenvalue analysis by using finite element method (FEM) is employed for computing Euler stress. The influence of various geometric and corrosion characteristics are investigated and it is found that the aspect ratio of the plate, the average thickness diminution, the standard deviation of thickness diminution and the amount of corrosion loss have influence on the reduction of buckling strength of the corroded plates. Buckling strength of one- and both-sided corroded plates are the same. In plates with low value of aspect ratio, reduction of buckling strength is negligible. Reduction of buckling strength is more prominent in plates with higher aspect ratio. Reduction of buckling strength is very sensitive to the amount of corrosion loss; the higher the amount of corrosion loss, the more reduction of buckling strength. Reduction of buckling strength is less sensitive to the standard deviation of thickness diminution.

  5. 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

  6. 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.

  7. 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.

  8. Modeling the Flexural Carrying Capacity of Corroded RC Beam

    Institute of Scientific and Technical Information of China (English)

    WANG Xiao-hui; LIU Xi-la

    2008-01-01

    Considering the change of bond strength between corroded steel and concrete, flexural carrying ca-pacity of corroded reinforced concrete (RC) beam was calculated. On the basis of the condition of equilibriumof forces and compatibility of deformations for the whole beam, a model for the prediction of flexural carryingcapacity of the corroded RC beam was proposed. Comparison of the model's predictions with the experimentalresults published in the literature shows the practicality of the proposed method.

  9. Corroded scale analysis from water distribution pipes

    Directory of Open Access Journals (Sweden)

    Rajaković-Ognjanović Vladana N.

    2011-01-01

    Full Text Available The subject of this study was the steel pipes that are part of Belgrade's drinking water supply network. In order to investigate the mutual effects of corrosion and water quality, the corrosion scales on the pipes were analyzed. The idea was to improve control of corrosion processes and prevent impact of corrosion on water quality degradation. The instrumental methods for corrosion scales characterization used were: scanning electron microscopy (SEM, for the investigation of corrosion scales of the analyzed samples surfaces, X-ray diffraction (XRD, for the analysis of the presence of solid forms inside scales, scanning electron microscopy (SEM, for the microstructural analysis of the corroded scales, and BET adsorption isotherm for the surface area determination. Depending on the composition of water next to the pipe surface, corrosion of iron results in the formation of different compounds and solid phases. The composition and structure of the iron scales in the drinking water distribution pipes depends on the type of the metal and the composition of the aqueous phase. Their formation is probably governed by several factors that include water quality parameters such as pH, alkalinity, buffer intensity, natural organic matter (NOM concentration, and dissolved oxygen (DO concentration. Factors such as water flow patterns, seasonal fluctuations in temperature, and microbiological activity as well as water treatment practices such as application of corrosion inhibitors can also influence corrosion scale formation and growth. Therefore, the corrosion scales found in iron and steel pipes are expected to have unique features for each site. Compounds that are found in iron corrosion scales often include goethite, lepidocrocite, magnetite, hematite, ferrous oxide, siderite, ferrous hydroxide, ferric hydroxide, ferrihydrite, calcium carbonate and green rusts. Iron scales have characteristic features that include: corroded floor, porous core that contains

  10. Oscillatory electrochemical reactions at corroding silicon surface

    Science.gov (United States)

    Parkhutik, Vitali; Sasano, Junji; Ogata, Yukio; Matveeva, Eugenia

    2003-05-01

    The paper analyses the nature of chaotic and well-ordered oscillations of the anodic potential and open circuit potential of silicon immersed in aqueous electrolytes. These oscillations are observed when experimental conditions are fine tuned in what corresponds to the current flowing through the system, composition of electrolyte, its viscosity, etc. It is assumed that the oscillations are due to the accumulation of mechanical stress in the thin (50-80 nm) oxide film formed at the surface of silicon as a result of electrochemical anodic reaction. The stress is released by local etching of the oxide and its lifting-on from the Si surface. The process repeats again and again yielding long-lasting oscillations of the anodic potential value (amplitude around 1-15 V, period 20-150 s) or of the open circuit potential (several hundreds milli-volts). Along with temporal ordering of the process (oscillations of potential) there occurs a spatial ordering in the system - the surface of corroding Si sample is covered with hexagonally ordered semi-spherical cells (diameter about 700 nm). The effect is well-fit by the general phenomenology of chaos-order transitions in che4mical systems (bifurcations), strange attractors are the intrinsic features of these oscillations) and its kinetics is very similar to that of the Belousov-Zabotinsky reaction. However, oscillatory processes on the corroding Si surface are caused by quite specific physical and chemical mechanisms, which are not well understood presently. We present the microscopic model for the oscillatory behavior which involves, generation of local mechanical stress at the Si/electrolyte interface, non-linear electrochemical etching of Si, localization of the electric field at the etched surface, etc.

  11. Elastic tripping analysis of corroded flat-bar stiffeners

    Directory of Open Access Journals (Sweden)

    Ahmad Rahbar-Ranji

    2016-12-01

    Full Text Available Tripping of stiffeners is one of the buckling modes of stiffened panel which could rapidly lead to its catastrophic failure. Loss of thickness in web and flange due to corrosion reduces elastic buckling strength of stiffeners. It is common practice to assume a uniform thickness reduction for general corrosion. Since the real corroded plate has rough surfaces, to estimate the remaining strength of corroded structures, typically a much higher level of accuracy is required. There is a little study on strength analysis of corroded plates with rough surface especially as a function of corrosion degrees. The aim of present work is to analyze elastic tripping stress of flat bar stiffeners with both-sided corroded surfaces. Undulated surfaces are generated based on the power spectrum of the corroded surface. Elastic tripping stress is calculated using ANSYS code. Finite elements method is employed to analyze elastic tripping stress of corroded steel flat bars with both sided rough surfaces. Comparing the results with elastic tripping strength of corroded flat bars with uniform thickness, a reduction factor is proposed. It is found that reduction factor of buckling strength by uniform thickness assumption is overestimated.

  12. Consideration on fatigue strength of corroded steel plates; Fushoku suimo koban no hiro kyodo ni kansuru ichikosatsu

    Energy Technology Data Exchange (ETDEWEB)

    Iwata, M.; Yajima, H.; Yamamoto, M.; Saito, T. [Hiroshima University, Hiroshima (Japan). Faculty of Engineering

    1996-10-01

    Discussions were given on fatigue strength of corroded steel plates taken from a hull of a ship seventeen years old after construction. The steel plates have had their original thickness of 13 mm reduced to 5.3 to 8.3 mm. After having been cut by a machine, the steel plates were used for tests as ground plates after going through grinding and as corroded plates with rust remaining on them. The fatigue test was performed in artificially made sea water at a temperature of 25{degree}C and in air with axial power pulsating tensile load and at iterative loading velocities of 3 to 5 Hz. The corroded material test verified that corrosion pits exist innumerably on the test piece surface and fatigue cracks have been developed and grown from bottoms of the pits. The stress concentration coefficient of the corrosion pits was about 1.9. Good agreement with the test result was found in the S-N chart in which the number of iteration of fracture was regarded as the number of iteratively generated cracks, and notch coefficient was estimated as 1.9. These results proved that the fatigue strength assessing method for virgin materials can be applied also to steel plates which have been exposed to corrosive environment for extended periods of time. 5 refs., 7 figs., 1 tab.

  13. Iron cycling at corroding carbon steel surfaces.

    Science.gov (United States)

    Lee, Jason S; McBeth, Joyce M; Ray, Richard I; Little, Brenda J; Emerson, David

    2013-01-01

    Surfaces of carbon steel (CS) exposed to mixed cultures of iron-oxidizing bacteria (FeOB) and dissimilatory iron-reducing bacteria (FeRB) in seawater media under aerobic conditions were rougher than surfaces of CS exposed to pure cultures of either type of microorganism. The roughened surface, demonstrated by profilometry, is an indication of loss of metal from the surface. In the presence of CS, aerobically grown FeOB produced tight, twisted helical stalks encrusted with iron oxides. When CS was exposed anaerobically in the presence of FeRB, some surface oxides were removed. However, when the same FeOB and FeRB were grown together in an aerobic medium, FeOB stalks were less encrusted with iron oxides and appeared less tightly coiled. These observations suggest that iron oxides on the stalks were reduced and solubilized by the FeRB. Roughened surfaces of CS and denuded stalks were replicated with culture combinations of different species of FeOB and FeRB under three experimental conditions. Measurements of electrochemical polarization resistance established different rates of corrosion of CS in aerobic and anaerobic media, but could not differentiate rate differences between sterile controls and inoculated exposures for a given bulk concentration of dissolved oxygen. Similarly, total iron in the electrolyte could not be used to differentiate treatments. The experiments demonstrate the potential for iron cycling (oxidation and reduction) on corroding CS in aerobic seawater media.

  14. Prediction of residual shear strength of corroded reinforced concrete beams

    Science.gov (United States)

    Imam, Ashhad; Azad, Abul Kalam

    2016-09-01

    With the aim of providing experimental data on the shear capacity and behavior of corroded reinforced concrete beams that may help in the development of strength prediction models, the test results of 13 corroded and four un-corroded beams are presented. Corrosion damage was induced by accelerated corrosion induction through impressed current. Test results show that loss of shear strength of beams is mostly attributable to two important damage factors namely, the reduction in stirrups area due to corrosion and the corrosion-induced cracking of concrete cover to stirrups. Based on the test data, a method is proposed to predict the residual shear strength of corroded reinforced concrete beams in which residual shear strength is calculated first by using corrosion-reduced steel area alone, and then it is reduced by a proposed reduction factor, which collectively represents all other applicable corrosion damage factors. The method seems to yield results that are in reasonable agreement with the available test data.

  15. Property of Corroded Concrete under Compressive Uniaxial Loads

    Institute of Scientific and Technical Information of China (English)

    FAN Yingfang; HU Zhiqiang; ZHOU Jing; LI Xin

    2008-01-01

    In order to study the compressive property of corroded concrete, accelerated corrosion test were performed on concrete C30.6 corrosive solutions, including hydraulic acid solution (pH=2), hydraulic acid solution (pH=3) were applied as the corrosive medium. 6 series of corrosion tests, including 111 specimens,were carried out. Mechanical properties of all the corroded specimens were tested respectively. Compressive properties of the corroded specimens (e.g. compressive strength, stress-strain relation, elastic modulus etc.) were achieved. Taking the strength degradation ratio and strain energy loss as damage index, effects of the corrosion solution on the compressive property of corroded concrete were discussed in detail. Relationship between the damage index and corrosion state of specimens were achieved.

  16. Surface area considerations for corroding N reactor fuel

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, A.B. Jr.; Pitner, A.L.

    1996-06-01

    The N Reactor fuel is corroding at sites where the Zircaloy cladding was damaged when the fuel was discharged from the reactor. Corroding areas are clearly visible on the fuel stored in open cans in the K East Basin. There is a need to estimate the area of the corroding uranium to analyze aspects of fuel behavior as it is transitioned. from current wet storage to dry storage. In this report, the factors that contribute to {open_quotes}true{close_quotes} surface area are analyzed in terms of what is currently known about the N Reactor fuel. Using observations from a visual examinations of the fuel in the K East wet storage facility, a value for the corroding geometric area is estimated. Based on observations of corroding uranium and surface roughness values for other metals, a surface roughness factor is also estimated and applied to the corroding K East fuel to provide an estimated {open_quotes}true{close_quotes} surface area. While the estimated area may be modified as additional data become available from fuel characterization studies, the estimate provides a basis to assess effects of exposed uranium metal surfaces on fuel behavior in operations involved in transitioning from wet to dry storage, during shipment and staging, conditioning, and dry interim storage.

  17. Buckling analysis of partially corroded steel plates with irregular surfaces

    Indian Academy of Sciences (India)

    Ahmad Rahbar-Ranji

    2014-04-01

    Corrosion is a long-term, inevitable process, lessens the thickness and load carrying capacity of structures. Old steel structures are more vulnerable to buckling, yielding and fracture due to corrosion. In lieu of a detailed analysis, average thickness assumption is employed for general type of corrosion. However, the estimation of load carrying capacity reduction of corroded structures typically need a much higher level of accuracy, since the actual corroded plates would have irregular surfaces. The objective of this article is to determine the effect of general corrosion on reduction of elastic buckling strength of both-sided partially corroded plates with irregular surfaces. Eigenvalue analysis using finite element method is employed for Euler stress calculation of corroded plates. The effects of different influential parameters are investigated and it is found that, aspect ratio of plate, location of corroded area, standard deviation of thickness diminution and concentration of corrosion have influence on reduction of elastic buckling strength. Reduction of elastic buckling strength is very sensitive to the amount of corrosion loss. The higher the amount of corrosion loss, the more reduction of elastic buckling strength.

  18. 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...

  19. Elastic buckling analysis of corroded stiffened plates with irregular surfaces

    Indian Academy of Sciences (India)

    Ahmad Rahbar-Ranji

    2015-02-01

    Numerical simulation is used to study the influence of corrosion damage in stiffened plates focusing on elastic buckling strength. Three-dimensional specta are used to simulate geometries of corroded surfaces and finite element method is employed for computing Euler stress of stiffened plates. The influence of corrosion patterns, amount of corrosion loss and roughness of surface are investigated. Ratio of Euler stress of corroded stiffened plate over Euler stress of un-corroded stiffened plate is used to characterize the effects of corrosion on reduction of buckling strength. Results show that reduction of buckling strength is very sensitive to the amount of corrosion loss and roughness of surface, but less sensitive to the location of corroded region. The potential for decrease in buckling strength as a consequence of corrosion is found to depend on the dominant buckling mode. Residual buckling strength is reduced by as much as 12% for the interaction of plate-web-torsional buckling mode, and by 2% for column buckling.

  20. 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.

  1. 49 CFR 195.587 - What methods are available to determine the strength of corroded pipe?

    Science.gov (United States)

    2010-10-01

    ... strength of corroded pipe? 195.587 Section 195.587 Transportation Other Regulations Relating to... methods are available to determine the strength of corroded pipe? Under § 195.585, you may use the... Pipe (with RSTRENG disk),” to determine the strength of corroded pipe based on actual remaining wall...

  2. An Analysis on Limit Load for Corroded Submarine Pipelines

    Institute of Scientific and Technical Information of China (English)

    TAN Kai-ren; XIAO Xi

    2006-01-01

    By means of elastic-plastic finite element analysis, a systematic nonlinear analysis of material and geometry has been carried out for submarine pipelines. A criterion for deriving limit load is studied. Based on this criterion, the limit load for corroded submarine pipelines is calculated. The corrosion length, corrosion depth and corrosion width affect the limit load. A solution to limit load is proposed and proved valid through comparison of the solution with burst test results and ASME B31G solutions.

  3. Corrosion damage evolution and residual strength of corroded aluminum alloys

    Institute of Scientific and Technical Information of China (English)

    Youhong Zhang; Guozhi Lv; Hui Wang; Bomei Si; Yueliang Cheng

    2008-01-01

    The LY12CZ aluminum alloy specimens were eurroded under the conditions of different test temperatures and exposure durations. After corrosion exposure, fatigue tests were performed. Scanning electron microscopy and optical microscope analyses on corrosion damage were carried out. The definition of surface corrosion damage ratio was provided to describe the extent of surface corrosion damage. On the basis of the measured data sets of the corrosion damage ratio, the probabilistic model of corrosion damage evolution was built. The corrosion damage decreased the fatigue life by a factor of about 1.25 to 2.38 and the prediction method of residual strength of the corroded structure was presented.

  4. Three-Dimensional Surface Parameters and Multi-Fractal Spectrum of Corroded Steel.

    Science.gov (United States)

    Shanhua, Xu; Songbo, Ren; Youde, Wang

    2015-01-01

    To study multi-fractal behavior of corroded steel surface, a range of fractal surfaces of corroded surfaces of Q235 steel were constructed by using the Weierstrass-Mandelbrot method under a high total accuracy. The multi-fractal spectrum of fractal surface of corroded steel was calculated to study the multi-fractal characteristics of the W-M corroded surface. Based on the shape feature of the multi-fractal spectrum of corroded steel surface, the least squares method was applied to the quadratic fitting of the multi-fractal spectrum of corroded surface. The fitting function was quantitatively analyzed to simplify the calculation of multi-fractal characteristics of corroded surface. The results showed that the multi-fractal spectrum of corroded surface was fitted well with the method using quadratic curve fitting, and the evolution rules and trends were forecasted accurately. The findings can be applied to research on the mechanisms of corroded surface formation of steel and provide a new approach for the establishment of corrosion damage constitutive models of steel.

  5. Three-Dimensional Surface Parameters and Multi-Fractal Spectrum of Corroded Steel.

    Directory of Open Access Journals (Sweden)

    Xu Shanhua

    Full Text Available To study multi-fractal behavior of corroded steel surface, a range of fractal surfaces of corroded surfaces of Q235 steel were constructed by using the Weierstrass-Mandelbrot method under a high total accuracy. The multi-fractal spectrum of fractal surface of corroded steel was calculated to study the multi-fractal characteristics of the W-M corroded surface. Based on the shape feature of the multi-fractal spectrum of corroded steel surface, the least squares method was applied to the quadratic fitting of the multi-fractal spectrum of corroded surface. The fitting function was quantitatively analyzed to simplify the calculation of multi-fractal characteristics of corroded surface. The results showed that the multi-fractal spectrum of corroded surface was fitted well with the method using quadratic curve fitting, and the evolution rules and trends were forecasted accurately. The findings can be applied to research on the mechanisms of corroded surface formation of steel and provide a new approach for the establishment of corrosion damage constitutive models of steel.

  6. Electrochemical Decontamination of Painted and Heavily Corroded Metals

    Energy Technology Data Exchange (ETDEWEB)

    Marczak, S.; Anderson, J.; Dziewinski, J.

    1998-09-08

    The radioactive metal wastes that are generated from nuclear fuel plants and radiochemical laboratories are mainly contaminated by the surface deposition of radioactive isotopes. There are presently several techniques used in removing surface contamination involving physical and chemical processes. However, there has been very little research done in the area of soiled, heavily oxidized, and painted metals. Researchers at Los Alamos National Laboratory have been developing electrochemical procedures for the decontamination of bare and painted metal objects. These methods have been found to be effective on highly corroded as well as relatively new metals. This study has been successful in decontaminating projectiles and shrapnel excavated during environmental restoration projects after 40+ years of exposure to the elements. Heavily corroded augers used in sampling activities throughout the area were also successfully decontaminated. This process has demonstrated its effectiveness and offers several advantages over the present metal decontamination practices of media blasting and chemical solvents. These advantages include the addition of no toxic or hazardous chemicals, low operating temperature and pressure, and easily scaleable equipment. It is in their future plans to use this process in the decontamination of gloveboxes destined for disposal as TRU waste.

  7. Collapse of Corroded Pipelines under Combined Tension and External Pressure.

    Directory of Open Access Journals (Sweden)

    Hao Ye

    Full Text Available In this work, collapse of corroded pipeline under combined external pressure and tension is investigated through numerical method. Axially uniform corrosion with symmetric imperfections is firstly considered. After verifying with existing experimental results, the finite element model is used to study the effect of tension on collapse pressure. An extensive parametric study is carried out using Python script and FORTRAN subroutine to investigate the influence of geometric parameters on the collapse behavior under combined loads. The results are used to develop an empirical equation for estimating the collapse pressure under tension. In addition, the effects of loading path, initial imperfection length, yielding anisotropy and corrosion defect length on the collapse behavior are also investigated. It is found that tension has a significant influence on collapse pressure of corroded pipelines. Loading path and anisotropic yielding are also important factors affecting the collapse behavior. For pipelines with relatively long corrosion defect, axially uniform corrosion models could be used to estimate the collapse pressure.

  8. Geochemical investigation of iron transport into bentonite as steel corrodes

    Energy Technology Data Exchange (ETDEWEB)

    Hunter, Fiona; Bate, Fiona; Heath, Tim; Hoch, Andrew [Serco Assurance, Harwe ll (United Kingdom)

    2007-09-15

    In Sweden and Finland, it is proposed that spent nuclear fuel will be encapsulated in sealed cylindrical canisters, for disposal in a geologic repository, either in vertical boreholes (KBS-3V) or in long horizontal boreholes (KBS-3H). The canisters will consist of a thick cast iron insert and a copper outer container, and each canister will be surrounded by a compacted bentonite clay buffer. It is important to investigate the possible consequences if a failure of these physical barriers was to occur. For instance, if mechanical failure of the copper outer container were to occur then groundwater could enter the annulus and reach the cast iron insert. This would result in anaerobically corroded iron from the cast iron insert interacting with the bentonite surrounding the canisters. The presence of anaerobically corroded iron in groundwater raises the question of how the bentonite will be affected by this process. In the case of the KBS-3H concept, mechanical failure of the copper outer container could lead to interaction between anaerobically corroded iron and bentonite, as above. However, direct contact between anaerobically corroding carbon steel and bentonite is also likely because of the presence of perforated carbon steel support structures in the long horizontal boreholes. As part of the NF-PRO project, an extensive experimental programme has been carried out over several years to study the interactions between anaerobically corroding carbon steel or cast iron and bentonite. The purpose of this report is to describe the modelling work that has been carried out, and the conclusions that have been reached. The experimental programme has carried out a series of long term experiments looking at anaerobic corrosion of carbon steel or cast iron in compacted MX80 bentonite at 30 deg C or 50 deg C. In the bentonite the concentration of iron decreased with increasing distance away from the iron-bentonite interface, with local iron concentrations as high as 20 wt % in

  9. Strengthening of Corroded Reinforced SCC-RAP Members with CFRP

    Directory of Open Access Journals (Sweden)

    Ahmed Abdel-Mohti

    2016-01-01

    Full Text Available Corrosion is one of the major problems affecting the durability of reinforced concrete (RC structures. This paper investigates the effect of rebar corrosion on the performance of reinforced self-consolidating concrete (SCC members and the effectiveness of repair. A control RC member, which has no corrosion problem, was prepared to compare against corroded and repaired members. A number of reinforced concrete members having up to 50% corrosion level were constructed and tested to study the effect of corrosion on the structural performance of RC members. The beams with corrosion problem were repaired using carbon fiber reinforced polymer (CFRP sheets and U-wraps. All of the beams constructed, which are either not repaired or repaired, in this study were tested under two static line loads until failure. The effect of corrosion and effectiveness of repairing technique were assessed by evaluating the performance in terms of load carrying capacity, deflection, and ductility. Test results revealed that as the corrosion level increases, the loss in load carrying capacity increases. Repairing using CFRP improved the performance of corroded members. For example, when 50% corrosion level was achieved, the beam lost approximately 57% of its load carrying capacity, but when it was repaired, it recovered about 42% of its load carrying capacity.

  10. 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...

  11. 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...

  12. 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 ...

  13. 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

  14. 49 CFR 195.585 - What must I do to correct corroded pipe?

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false What must I do to correct corroded pipe? 195.585... pipe? (a) General corrosion. If you find pipe so generally corroded that the remaining wall thickness... pipe. However, you need not replace the pipe if you— (1) Reduce the maximum operating pressure...

  15. Microstructural Features in Corroded Celtic Iron Age Sword Blades

    Science.gov (United States)

    Ghiara, G.; Piccardo, P.; Campodonico, S.; Carnasciali, M. M.

    2014-05-01

    Archaeological artefacts made from iron and steel are often of critical importance for archaeometallurgical studies, which aim to understand the process of manufacturing, as the nearly complete alloy mineralization does not allow for any type of metallographic interpretation. In this study, three Iron Age sword blades dated from the second century BC (LaTène B2/D1) found in the archaeological site of Tintignac (Commune de Naves, Corrèze, France), were investigated. A multianalytical approach was employed to acquire a complete range of data from the partially or totally corroded objects. Analyses were carried out with the use of light optical microscopy, micro Raman spectroscopy, and scanning electron microscopy equipped with energy-dispersive x-ray spectroscopy (EDXS). Remnants of metallographic features—ghost microstructure—in the corrosion layers of the blades were observed, allowing for a partial reconstruction of the manufacturing process.

  16. Seismic Behavior of Corroded RC Bridges: Review and Research Gaps

    Directory of Open Access Journals (Sweden)

    Kaveh Andisheh

    2016-01-01

    Full Text Available Chloride-induced corrosion and its effect on structural and seismic performance of reinforced concrete (RC structures have been the topic of several research projects in past decades. This literature review summarizes the state of the art by presenting a brief description of chloride-induced corrosion, its main characteristics and influencing factors, a summary of experimental published data, and existing corrosion-induced deterioration models together with numerical and experimental methods used to evaluate corroded RC bridge pier. This literature review highlights the need for reliable deterioration models for RC structures and appropriate analysis methods are needed for design of new structures or assessment of existing civil engineering structures especially in seismic areas.

  17. 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.

  18. 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.

  19. 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

  20. Finite Element Calculation of the Flexural Stiffness of Corroded RC Eccentric Compressive Members

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hua; WEI Jun; PAN Qiao; HUANG Ying

    2010-01-01

    A finite element calculation model of corroded RC eccentric compressive members was build using finite element software ANSYS. The model considers the decline of mechanical properties and the effective section of a corroded steel bar, as well as the deterioration of bond character between corroded reinforcement and concrete. The reliability of the finite element model was evaluated by comparing the results of the finite element calculation with the data from experiments. Based on the finite element analysis results, the influence of corrosion degree, the diameter change of the longitudinal reinforcing bars and the spacing change of stirrups on the flexural stiffness were calculated and analyzed.

  1. Computational Modelling Strategies for Nonlinear Response Prediction of Corroded Circular RC Bridge Piers

    Directory of Open Access Journals (Sweden)

    Mohammad M. Kashani

    2016-01-01

    Full Text Available A numerical model is presented that enables simulation of the nonlinear flexural response of corroded reinforced concrete (RC components. The model employs a force-based nonlinear fibre beam-column element. A new phenomenological uniaxial material model for corroded reinforcing steel is used. This model accounts for the impact of corrosion on buckling strength, postbuckling behaviour, and low-cycle fatigue degradation of vertical reinforcement under cyclic loading. The basic material model is validated through comparison of simulated and observed responses for uncorroded RC columns. The model is used to explore the impact of corrosion on the inelastic response of corroded RC columns.

  2. 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.

  3. 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.

  4. Right Hemisphere Brain Damage

    Science.gov (United States)

    ... or hemispheres. Each hemisphere is responsible for different body functions and skills. In most people, the left side of the brain contains the person's language functions. The right side contributes to a number ...

  5. Monitoring and Failure Analysis of Corroded Bridge Cables under Fatigue Loading Using Acoustic Emission Sensors

    Directory of Open Access Journals (Sweden)

    Hui Li

    2012-03-01

    Full Text Available Cables play an important role in cable-stayed systems, but are vulnerable to corrosion and fatigue damage. There is a dearth of studies on the fatigue damage evolution of corroded cable. In the present study, the acoustic emission (AE technology is adopted to monitor the fatigue damage evolution process. First, the relationship between stress and strain is determined through a tensile test for corroded and non-corroded steel wires. Results show that the mechanical performance of corroded cables is changed considerably. The AE characteristic parameters for fatigue damage are then established. AE energy cumulative parameters can accurately describe the fatigue damage evolution of corroded cables. The failure modes in each phase as well as the type of acoustic emission source are determined based on the results of scanning electron microscopy. The waveform characteristics, damage types, and frequency distribution of the corroded cable at different damage phases are collected. Finally, the number of broken wires and breakage time of the cables are determined according to the variation in the margin index.

  6. Monitoring and failure analysis of corroded bridge cables under fatigue loading using acoustic emission sensors.

    Science.gov (United States)

    Li, Dongsheng; Ou, Jinping; Lan, Chengming; Li, Hui

    2012-01-01

    Cables play an important role in cable-stayed systems, but are vulnerable to corrosion and fatigue damage. There is a dearth of studies on the fatigue damage evolution of corroded cable. In the present study, the acoustic emission (AE) technology is adopted to monitor the fatigue damage evolution process. First, the relationship between stress and strain is determined through a tensile test for corroded and non-corroded steel wires. Results show that the mechanical performance of corroded cables is changed considerably. The AE characteristic parameters for fatigue damage are then established. AE energy cumulative parameters can accurately describe the fatigue damage evolution of corroded cables. The failure modes in each phase as well as the type of acoustic emission source are determined based on the results of scanning electron microscopy. The waveform characteristics, damage types, and frequency distribution of the corroded cable at different damage phases are collected. Finally, the number of broken wires and breakage time of the cables are determined according to the variation in the margin index.

  7. 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.

  8. Surface investigation of naturally corroded gilded copper-based objects

    Energy Technology Data Exchange (ETDEWEB)

    Ingo, G.M., E-mail: gabriel.ingo@ismn.cnr.it [Istituto per lo Studio dei Materiali Nanostrutturati—Consiglio Nazionale delle Ricerche (ISMN—CNR), Area della Ricerca del CNR Roma1-Montelibretti, via Salaria Km 29.3, 00016 Monterotondo Scalo, Rome (Italy); Riccucci, C. [Istituto per lo Studio dei Materiali Nanostrutturati—Consiglio Nazionale delle Ricerche (ISMN—CNR), Area della Ricerca del CNR Roma1-Montelibretti, via Salaria Km 29.3, 00016 Monterotondo Scalo, Rome (Italy); Lavorgna, M.; Salzano de Luna, M. [Istituto per i Polimeri, Compositi e Biomateriali—Consiglio Nazionale delle Ricerche (IPCB—CNR), P.le E. Fermi 1, 80050 Portici, Napoli (Italy); Pascucci, M. [Istituto per lo Studio dei Materiali Nanostrutturati—Consiglio Nazionale delle Ricerche (ISMN—CNR), Area della Ricerca del CNR Roma1-Montelibretti, via Salaria Km 29.3, 00016 Monterotondo Scalo, Rome (Italy); Di Carlo, G., E-mail: gabriella.dicarlo@ismn.cnr.it [Istituto per lo Studio dei Materiali Nanostrutturati—Consiglio Nazionale delle Ricerche (ISMN—CNR), Area della Ricerca del CNR Roma1-Montelibretti, via Salaria Km 29.3, 00016 Monterotondo Scalo, Rome (Italy)

    2016-11-30

    Highlights: • Naturally corroded Au and Ag coated Cu-based objects studied by XPS, SEM + EDS and OM. • The main degrading agents are Cl, S and P species from surrounding environment. • Metal galvanic coupling enhances corrosion phenomena. • Corrosion forms a layered patina of noble metal remains, soil components and Cu{sub 2}O. • Useful information to tailor safe cleaning and reliable conservation strategies. - Abstract: Gold and silver coated copper-based artefacts subjected to long-term natural corrosion phenomena were studied by means of the combined use of X-ray photoelectron spectroscopy (XPS), scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM + EDS), and optical microscopy (OM). The results allowed the identification of the chemistry and structure of the Au or Ag layers deposited by fire-gilding or mercury-silvering and the determination of the corrosion products formed due to interaction with the surrounding environment. Different degradation phenomena of the noble metal layer and copper substrate are induced by the presence of chlorine, sulphur and phosphorous and they are boosted by the metal galvanic coupling which makes gilded-metal art works unstable from a chemico-physical point of view. The SEM + EDS and OM results also suggest that particular care must be used during the removal of the encrustations and of the external corrosion products to avoid the loss of the remains of the noble layer often floating or embedded in the corrosion products. Furthermore, in order to avoid the reaction between nantokite (CuCl) and moisture the use no or low toxic inhibitors is suggested to avoid further severe degradation phenomena enhancing the long-lasting chemico-physical stability of these precious artefacts and giving them a greater chance of survival.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 预应力与非预应力AFRP加固腐蚀钢筋混凝土梁疲劳性能研究%Experimental study on fatigue performance corroded reinforced concrete beams strengthened with prestressed AFRP sheets

    Institute of Scientific and Technical Information of China (English)

    邓宗才; 李凯

    2009-01-01

    to estimate an equivalent fatigue notch factor for the main reinforcement bars of the tested specimens. Pitting corrosion resulted in an increase in the fatigue notch factor, which in turn resulted in a significant reduction of fatigue life. Based on the experimental results of moderate corroded concrete beams strengthened with AFRP sheets, the fatigue equation was obtained, and this equation can be used in strengthened design for damaged bridge.

  14. Study of the behavior of corroded steel bar and convenient method of repairing

    Directory of Open Access Journals (Sweden)

    Nihal Abdelhamid Taha

    2016-08-01

    Full Text Available This paper presents an experimental investigation into the residual strength and mechanical properties of corroded reinforcing bare bars. An attempt has been made to describe firstly the impressed current technique which is commonly used for accelerating reinforcement corrosion. The study compared between two methods of repairing the corroded steel bar, the first one which mostly used by painting the half surface area of corroded bar; and the another one by coating the full surface area of corroded bar. The experimental results show that, the corrosion process alters the external surface of steel bar due to pitting, the residual cross-section of the corroded bar is no longer round and varies considerably along its circumference and its length so the residual diameter is better defined by loss of weight. The rate of corrosion has been calculated by two terms, the term of mass loss rate (MR and the term of penetration rate (CR. The mass loss rate decreased for fully coated bars by 1.7–2 times than half coated bars showing the importance of fully coating bars in corrosion repair. Finally, the reliability of using the galvanostatic method in research work was represented by comparing between the real time and the accelerated time to reach a certain degree of corrosion.

  15. 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.

  16. 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.

  17. 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

  18. 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...

  19. 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.

  20. 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

  1. In-situ test methods for assessment of surface pH of corroding sewer pipes

    DEFF Research Database (Denmark)

    Nielsen, Asbjørn Haaning; Vollertsen, Jes

    A method for measuring the surface pH of corroding concrete was developed in the lab and tested in the field. The method is based on direct application of pH indicator solution on the corroding surfaces. Comparison against point measurements using a flat surface pH electrode (flatrode) confirmed...... the accuracy of the method. Blind testing of concrete specimens exposed to different acid concentrations demonstrated that it was possible to determine the surface pH within ±0.5 pH units in the pH range of one to five. The developed method provides a simple and reliable estimate on the extent of concrete...

  2. 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/.

  3. 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

  4. Southern hemisphere observations

    Science.gov (United States)

    Orchiston, Wayne

    Because of insurmountable problems associated with absolute dating, the non-literate cultures of the Southern Hemisphere can contribute little to Applied Historical Astronomy, although Maori traditions document a possible supernova dating to the period 1000-1770 AD. In contrast, the abundant nineteenth century solar, planetary, cometary and stellar observational data provided by Southern Hemisphere professional and amateur observatories can serve as an invaluable mine of information for present-day astronomers seeking to incorporate historical data in their investigations.

  5. Low cycle fatigue of corroded pipes under cyclic bending and internal pressure

    Energy Technology Data Exchange (ETDEWEB)

    Lourenco, Marcelo Igor; Netto, Theodoro A. [Universidade Federal do Rio de Janeiro COPPE - Ocean Engineering Dept., Rio de Janeiro, RJ (Brazil)

    2010-07-01

    In oil and gas pipelines, fatigue failure can occur in corroded pipes after some years of operation. Thus it is important for operators to be able to evaluate the defects caused by corrosion to decide whether or not to repair the line. The ratcheting phenomenon can occur in parts of the pipes where corrosion has thickened the wall. The aim of this paper is to provide a new model for estimating resistance in corroded pipes which takes into account the ratcheting phenomenon. A 3-D finite element model was developed with ABACUS and experimental tests were carried out. Results showed that ratcheting should be considered in corroded pipes depending on the loading and on the size of the defect. In addition the model showed good correlation for the deformations presented in the first bending loading cycle but it did not anticipate ratcheting in the deepest defect. This paper demonstrated that ratcheting should be accounted for when analyzing the structural integrity of a corroded pipe.

  6. Growth kinetics of hydrogen sulfide oxidizing bacteria in corroded concrete from sewers

    NARCIS (Netherlands)

    Jensen, H.S.; Lens, P.N.L.; Nielsen, J.L.; Bester, K.; Nielsen, A.H.; Hvitved-Jacobsen, Th.; Vollertsen, J.

    2011-01-01

    Hydrogen sulfide oxidation by microbes present on concrete surfaces of sewer pipes is a key process in sewer corrosion. The growth of aerobic sulfur oxidizing bacteria from corroded concrete surfaces was studied in a batch reactor. Samples of corrosion products, containing sulfur oxidizing bacteria,

  7. Metagenome Analyses of Corroded Concrete Wastewater Pipe Biofilms Reveals a Complex Microbial System

    Science.gov (United States)

    Analysis of whole-metagenome pyrosequencing data and 16S rRNA gene clone libraries was used to determine microbial composition and functional genes associated with biomass harvested from crown (top) and invert (bottom) sections of a corroded wastewater pipe. Taxonomic and functio...

  8. Hemispheric contributions to pragmatics.

    Science.gov (United States)

    Zaidel, E; Kasher, A; Soroker, N; Batori, G; Giora, R; Graves, D

    2000-01-01

    Twenty-seven patients with right-hemisphere damage (RBD) and thirty-one patients with left-hemisphere damage (LBD) received a new pragmatics battery in Hebrew consisting of two parts: (1) comprehension and production of basic speech acts (BSAs), including tests of assertions, questions, requests, and commands, and (2) comprehension of implicatures, including implicatures of quantity, quality, relevance, and manner. Each test had a verbal and a nonverbal version. Patients also received Hebrew versions of the Western Aphasia Battery and of the Right Hemisphere Communication Battery. Both LBD and RBD patients were impaired relative to controls but did not differ from each other in their overall scores on BSAs and on Implicatures when scores were corrected by aphasia and neglect indices. There was a systematic localization of BSAs in the left hemisphere (LH) but not in the right hemisphere (RH). There was poor localization of Implicatures in either hemisphere. In LBD patients, BSAs were associated with language functions measured with the WAB, suggesting the radical possibility that the classic localization of language functions in aphasia is influenced by the localization of the BSAs required by aphasia language tests. Both BSAs and implicatures show greater functional independence from other pragmatic, language and cognitive functions in the RBD than in the LBD patients. Thus, the LH is more likely to contain an unmodular domain-nonspecific set of central cognitive mechanisms for applying means-ends rationality principles to intentional activity.

  9. Hemispherical Laue camera

    Science.gov (United States)

    Li, James C. M.; Chu, Sungnee G.

    1980-01-01

    A hemispherical Laue camera comprises a crystal sample mount for positioning a sample to be analyzed at the center of sphere of a hemispherical, X-radiation sensitive film cassette, a collimator, a stationary or rotating sample mount and a set of standard spherical projection spheres. X-radiation generated from an external source is directed through the collimator to impinge onto the single crystal sample on the stationary mount. The diffracted beam is recorded on the hemispherical X-radiation sensitive film mounted inside the hemispherical film cassette in either transmission or back-reflection geometry. The distances travelled by X-radiation diffracted from the crystal to the hemispherical film are the same for all crystal planes which satisfy Bragg's Law. The recorded diffraction spots or Laue spots on the film thereby preserve both the symmetry information of the crystal structure and the relative intensities which are directly related to the relative structure factors of the crystal orientations. The diffraction pattern on the exposed film is compared with the known diffraction pattern on one of the standard spherical projection spheres for a specific crystal structure to determine the orientation of the crystal sample. By replacing the stationary sample support with a rotating sample mount, the hemispherical Laue camera can be used for crystal structure determination in a manner previously provided in conventional Debye-Scherrer cameras.

  10. 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.

  11. 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.

  12. 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...

  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...... 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...

  14. Unilateral Hemispheric Encephalitis

    Directory of Open Access Journals (Sweden)

    Mohan Leslie Noone

    2014-10-01

    Full Text Available A 10 year old boy presented with history of mild fever and upper respiratory symptoms followed by recurrent seizures and loss of consciousness on the next day. Normal blood counts and abnormal hepatic transaminases were noted. MRI of the brain, done on the fourth day of illness, showed extensive involvement of the cortex in the right hemisphere. Lumbar CSF was normal. The EEG showed bilateral slowing with frontal sharp wave discharges and marked attenuation over the entire right hemisphere. The patient succumbed to the illness on the ninth day. A similar pattern of acute unilateral hemispheric cortical involvement is described in the hemiconvulsion-hemiplegia-epilepsy (HHE syndrome, which is typically described to occur in children below 4 years of age. This case of fulminant acute unilateral encaphilitic illness could represent the acute phase of HHE syndrome.

  15. 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

  16. 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...

  17. 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...

  18. 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.

  19. 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

  20. 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.

  1. Characterization and in vivo evaluation of a bio-corrodible nitrided iron stent.

    Science.gov (United States)

    Feng, Qimao; Zhang, Deyuan; Xin, Chaohua; Liu, Xiangdong; Lin, Wenjiao; Zhang, Wanqian; Chen, Sun; Sun, Kun

    2013-03-01

    A bio-corrodible nitrided iron stent was developed using a vacuum plasma nitriding technique. In the nitrided iron stents, the tensile strength, radial strength, stiffness and in vitro electrochemical corrosion rate were significantly increased compared with those of the control pure iron stent. To evaluate its performance in vivo, the deployment of the nitrided iron stents in juvenile pig iliac arteries was performed. At 3 or 6 months postoperatively, the stented vessels remained patent well; however, slight luminal loss resulting from intimal hyperplasia and relative stenosis of the stented vessel segment with piglets growth were observed by 12 months; no thrombosis or local tissue necrosis was found. At 1 month postoperatively, a nearly intact layer of endothelial cells formed on the stented vessel wall. Additionally, a decreased inflammation scoring, considerably corroded struts and corrosion products accumulation were seen. These findings indicate the potential of this nitrided iron stent as an attractive biodegradable stent.

  2. Effects of Oxygen on Biodegradation of Fuels in a Corroding Environment

    Science.gov (United States)

    2013-06-12

    known to be more labile than hydrocarbons to anaerobic biodegradation (Aktas, et al, 2010), so the preferential loss of these peaks from the...the contention that hydrocarbon removal was due at least in part to biodegradation by seawater microorganisms. Benzoate, cresols and alkanoic acids...RESPONSIBLE PERSON 19b. TELEPHONE NUMBER (Include area code) · Oxygen Effects on Biodegradation of Fuels in a Corroding Environment Deniz F. Aktas

  3. 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...

  4. 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...

  5. Relating Corroded Seven-Strand, Posttensioned Cable Cross-Sectional Properties to Load Capacity

    Directory of Open Access Journals (Sweden)

    Richard Haskins

    2016-01-01

    Full Text Available Multistrand anchors have seen widespread use, providing strength and stability at hydraulic Corps facilities. However, these steel tendons are subject to strength reduction as an effect of corrosion. Methods for evaluating the corroded cable strength do not exist to accurately estimate the time until tendon cables would have to be replaced (at great expense. The following five research tasks are used to address this deficiency: laboratory accelerated corrosion; pull-tests on pristine and laboratory corroded cables; optical scanning; data collection correlated with cross-sectional properties of cables; and development of a method to relate this data to the field. The pull-tests provide measured capacities for seven-strand, posttensioned (PT cables. An optical scan of the corroded cables provides cross-sectional properties of individual wires within the pulled cables. Trendlines are established for the related peak cable capacities and cross-sectional properties in an effort to determine their correlations. Trendlines for minimum wire area and second-moment short axis diameter are found with low error, making them good predictors of loaded cable capacity. This pull-test dataset has been related back to cable failure in the field, assuming a linear rate of corrosion loss for the cross-sectional properties and required PT capacity.

  6. 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.

  7. Electrochemical behavior of corroded and protected construction steel in cement extract

    Energy Technology Data Exchange (ETDEWEB)

    Koleva, D.A. [Delft University of Technology, Faculty of Civil Engineering and Geosciences, Section Materials and Environment, Stevinweg 1, 2628 CN Delft (Netherlands)

    2011-03-15

    The corrosion behavior of corroded, cathodically protected and control (reference) construction steel, previously embedded in concrete, was studied in cement extract (pH 12.6, considered as concrete pore water), using cyclic voltammetry (CVA) and potentiodynamic polarization (PDP). The necessity for this investigation occurred from the previously observed and commented discrepancies in the recorded corrosion parameters for corroded and protected steel in embedded conditions 1. Therefore this study aimed to evaluate how the ''naturally'' formed in concrete product layers (after 460 days) will influence the electrochemical behavior of the steel in cement extract. The PDP measurements reveal the lowest corrosion resistance to be for the previously corroded steel samples, for which the most active corrosion potential (-0.7 V SCE) and the highest anodic current in the potential region 0 to 0.6 V (SCE) were recorded. The CVA tests support the results from PDP and correlate the properties of the naturally formed layers with the recorded peak current densities and peak potentials with cycling. For all specimens, except the corroded ones, the peak potential initially shifts anodically, which denotes for a high corrosion resistance in the former and low corrosion resistance in the latter case. For the control and protected specimens, the passive current in the potential region of 0 to 0.6 V (SCE) remains almost unchanged with cycling, i.e. the protective properties of the initial layers remain unchanged. Thickening of the film with cycling does not influence the corrosion resistance of the previously formed layers. For the protected specimens, however, a tendency to reach a steady state and change of peak currents' height only were observed, without a pronounced shift to more anodic values. An increase in the peak current only, not accompanied by anodic shift of the peak potential, suggests that the layers in the cathodically protected specimens are

  8. Brain Hemisphericity and Developmental Dyslexia

    Science.gov (United States)

    Vlachos, Filippos; Andreou, Eleni; Delliou, Afroditi

    2013-01-01

    The present study examined the link between brain hemisphericity and dyslexia in secondary school students, using the Preference Test (PT), a widely used self-report index of preferred hemisphere thinking styles. The hypothesis was that differences would be revealed between the dyslexic group and their peers in hemispheric preference. A total of…

  9. 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...

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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...

  16. 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.

  17. Mechanical Performance versus Corrosion Damage Indicators for Corroded Steel Reinforcing Bars

    Directory of Open Access Journals (Sweden)

    Silvia Caprili

    2015-01-01

    Full Text Available The experimental results of a testing campaign including tensile and low-cycle fatigue tests on different reinforcing steel bar types in the as-delivered and corroded condition are presented. Experimental data were statistically analyzed adopting ANOVA technique; Performance Indicators (PIs, describing the mechanical performance characteristics of reinforcements, and Corrosion Damage Indicators (CDIs, describing the detrimental effects of corrosion phenomena, were determined and correlated in order to evaluate the influence of corrosion on the behaviour of reinforcing steels, providing useful information for designers in addition to what is presented in current standards.

  18. Succession of sulfur-oxidizing bacteria in the microbial community on corroding concrete in sewer systems.

    Science.gov (United States)

    Okabe, Satoshi; Odagiri, Mitsunori; Ito, Tsukasa; Satoh, Hisashi

    2007-02-01

    Microbially induced concrete corrosion (MICC) in sewer systems has been a serious problem for a long time. A better understanding of the succession of microbial community members responsible for the production of sulfuric acid is essential for the efficient control of MICC. In this study, the succession of sulfur-oxidizing bacteria (SOB) in the bacterial community on corroding concrete in a sewer system in situ was investigated over 1 year by culture-independent 16S rRNA gene-based molecular techniques. Results revealed that at least six phylotypes of SOB species were involved in the MICC process, and the predominant SOB species shifted in the following order: Thiothrix sp., Thiobacillus plumbophilus, Thiomonas intermedia, Halothiobacillus neapolitanus, Acidiphilium acidophilum, and Acidithiobacillus thiooxidans. A. thiooxidans, a hyperacidophilic SOB, was the most dominant (accounting for 70% of EUB338-mixed probe-hybridized cells) in the heavily corroded concrete after 1 year. This succession of SOB species could be dependent on the pH of the concrete surface as well as on trophic properties (e.g., autotrophic or mixotrophic) and on the ability of the SOB to utilize different sulfur compounds (e.g., H2S, S0, and S2O3(2-)). In addition, diverse heterotrophic bacterial species (e.g., halo-tolerant, neutrophilic, and acidophilic bacteria) were associated with these SOB. The microbial succession of these microorganisms was involved in the colonization of the concrete and the production of sulfuric acid. Furthermore, the vertical distribution of microbial community members revealed that A. thiooxidans was the most dominant throughout the heavily corroded concrete (gypsum) layer and that A. thiooxidans was most abundant at the highest surface (1.5-mm) layer and decreased logarithmically with depth because of oxygen and H2S transport limitations. This suggested that the production of sulfuric acid by A. thiooxidans occurred mainly on the concrete surface and the

  19. 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.

  20. 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.

  1. 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...

  2. 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.

  3. 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.

  4. [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.

  5. 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.

  6. Quantitative sensing of corroded steel rebar embedded in cement mortar specimens using ultrasonic testing

    Science.gov (United States)

    Owusu Twumasi, Jones; Le, Viet; Tang, Qixiang; Yu, Tzuyang

    2016-04-01

    Corrosion of steel reinforcing bars (rebars) is the primary cause for the deterioration of reinforced concrete structures. Traditional corrosion monitoring methods such as half-cell potential and linear polarization resistance can only detect the presence of corrosion but cannot quantify it. This study presents an experimental investigation of quantifying degree of corrosion of steel rebar inside cement mortar specimens using ultrasonic testing (UT). A UT device with two 54 kHz transducers was used to measure ultrasonic pulse velocity (UPV) of cement mortar, uncorroded and corroded reinforced cement mortar specimens, utilizing the direct transmission method. The results obtained from the study show that UPV decreases linearly with increase in degree of corrosion and corrosion-induced cracks (surface cracks). With respect to quantifying the degree of corrosion, a model was developed by simultaneously fitting UPV and surface crack width measurements to a two-parameter linear model. The proposed model can be used for predicting the degree of corrosion of steel rebar embedded in cement mortar under similar conditions used in this study up to 3.03%. Furthermore, the modeling approach can be applied to corroded reinforced concrete specimens with additional modification. The findings from this study show that UT has the potential of quantifying the degree of corrosion inside reinforced cement mortar specimens.

  7. Residual strength evaluation of corroded pipelines with long defects based upon limit load analysis

    Energy Technology Data Exchange (ETDEWEB)

    Chiodo, Mario S.G.; Ruggieri, Claudio [Universidade de Sao Paulo (USP), SP (Brazil). Dept. de Arquitetura Naval e Engenharia Oceanica

    2009-07-01

    Accurate evaluation of the residual strength for corroded pipes remains essential in fitness for service analyses, including repair decisions and life-extension programs, of onshore and offshore oil and gas transportation. As the pipeline infrastructure ages, material loss due to corrosion represents one of the main degradation factors of steel pipes which leads to strength reduction and potential catastrophic failures. Current high resolution methods can precisely measure the geometry of corrosion defects. Despite the improvement of those techniques, they are insufficient to ensure high levels of reliability in the burst pressure assessment because the recognized semi-empirical nature of conventional procedures. This work studies the applicability of a stress based criterion based upon plastic instability to predict the burst pressure of pipelines with axial corrosion defects. Verification studies based on experimental burst tests of large diameter pipes made of API X65 and X100 steels with different defect length showed the effectiveness of the proposed criterion based on {sigma}{sup ref} ={eta}{sigma}{sub u} in failure predictions, even though the {eta} factor exhibits a potential strong dependence of the defect geometry and material properties. In general, the results presented here provide an effective support to the ability of the proposed stress based criterion in the integrity assessment of corroded pipelines. (author)

  8. Characterization of U(VI)-phases in corroded cement products by micro(μ)-spectroscopic methods

    Science.gov (United States)

    Rothe, J.; Brendebach, B.; Bube, C.; Dardenne, K.; Denecke, M. A.; Kienzler, B.; Metz, V.; Prüßmann, T.; Rickers-Appel, K.; Schild, D.; Soballa, E.; Vitova, T.

    2013-04-01

    Cementation is an industrial scale conditioning method applied to fix and solidify liquid low and intermediate level radioactive wastes (LLW/ILW) prior to underground disposal in geological formations.To assist prognosis of the long-term safety of cemented waste, alteration of uranium doped cement productswas studied in chloride-rich solutions relevant for final LLW/ILW disposal in rock salt. After long-time exposure of the full-scale LLW/ILW simulates to concentrated NaCl and MgCl2 brines, solid samples were retrieved for chemical and mineralogical analysis with an emphasis on uranium speciation in the corroded cement matrix.Bulk and recent spatially resolved micro(μ) U L3-XAFS measurements point to the occurrence of a diuranate type U(VI) phase forming throughout the corroded cement monoliths. U-enriched hot spots with dimensions up to several tens of μm turn out to be generally X-ray amorphous.

  9. Dealloying evidence on corroded brass by laser-induced breakdown spectroscopy mapping and depth profiling measurements

    Science.gov (United States)

    Cerrato, R.; Casal, A.; Mateo, M. P.; Nicolas, G.

    2017-04-01

    The dealloying phenomenon, also called demetalification, is a; consequence of a corrosion problem found in binary alloys where an enrichment of one of the two main elements of the alloy is produced at the expense of the leaching of the other element. In the present work, the ability of laser induced breakdown spectroscopy (LIBS) for the detection and characterization of dealloying films formed on metal has been tested. For this purpose, specific areas of brass specimens have been subjected to a chemical attack of the surface in order to produce a selective leaching of zinc or dezincification. For the lateral and in-depth characterization of the dealloyed areas by LIBS, depth profiles, 2D and 3D maps have been generated from the treated samples and from a reference non-treated sample. The differences in the maps and depth profiles between the corroded and non-corroded regions have allowed to reveal the localization and extension of the dealloying process along the brass sample surface and to estimate the thickness of the dezincification layers, demonstrating the capability of LIBS technique for the characterization of dealloying phenomena.

  10. Growth kinetics of hydrogen sulfide oxidizing bacteria in corroded concrete from sewers.

    Science.gov (United States)

    Jensen, Henriette Stokbro; Lens, Piet N L; Nielsen, Jeppe L; Bester, Kai; Nielsen, Asbjørn Haaning; Hvitved-Jacobsen, Thorkild; Vollertsen, Jes

    2011-05-30

    Hydrogen sulfide oxidation by microbes present on concrete surfaces of sewer pipes is a key process in sewer corrosion. The growth of aerobic sulfur oxidizing bacteria from corroded concrete surfaces was studied in a batch reactor. Samples of corrosion products, containing sulfur oxidizing bacteria, were suspended in aqueous solution at pH similar to that of corroded concrete. Hydrogen sulfide was supplied to the reactor to provide the source of reduced sulfur. The removal of hydrogen sulfide and oxygen was monitored. The utilization rates of both hydrogen sulfide and oxygen suggested exponential bacterial growth with median growth rates of 1.25 d(-1) and 1.33 d(-1) as determined from the utilization rates of hydrogen sulfide and oxygen, respectively. Elemental sulfur was found to be the immediate product of the hydrogen sulfide oxidation. When exponential growth had been achieved, the addition of hydrogen sulfide was terminated leading to elemental sulfur oxidation. The ratio of consumed sulfur to consumed oxygen suggested that sulfuric acid was the ultimate oxidation product. To the knowledge of the authors, this is the first study to determine the growth rate of bacteria involved in concrete corrosion with hydrogen sulfide as source of reduced sulfur.

  11. Growth kinetics of hydrogen sulfide oxidizing bacteria in corroded concrete from sewers

    Energy Technology Data Exchange (ETDEWEB)

    Jensen, Henriette Stokbro, E-mail: h.s.jensen@sheffield.ac.uk [Department of Biotechnology, Chemistry and Environmental Engineering, Aalborg University, Sohngaardsholmsvej 57, 9000 Aalborg (Denmark); Lens, Piet N.L. [Sub-department of Environmental Technology, Agricultural University of Wageningen, Bomenweg 2, NL-6700-EV Wageningen (Netherlands); Nielsen, Jeppe L.; Bester, Kai; Nielsen, Asbjorn Haaning; Hvitved-Jacobsen, Thorkild; Vollertsen, Jes [Department of Biotechnology, Chemistry and Environmental Engineering, Aalborg University, Sohngaardsholmsvej 57, 9000 Aalborg (Denmark)

    2011-05-30

    Hydrogen sulfide oxidation by microbes present on concrete surfaces of sewer pipes is a key process in sewer corrosion. The growth of aerobic sulfur oxidizing bacteria from corroded concrete surfaces was studied in a batch reactor. Samples of corrosion products, containing sulfur oxidizing bacteria, were suspended in aqueous solution at pH similar to that of corroded concrete. Hydrogen sulfide was supplied to the reactor to provide the source of reduced sulfur. The removal of hydrogen sulfide and oxygen was monitored. The utilization rates of both hydrogen sulfide and oxygen suggested exponential bacterial growth with median growth rates of 1.25 d{sup -1} and 1.33 d{sup -1} as determined from the utilization rates of hydrogen sulfide and oxygen, respectively. Elemental sulfur was found to be the immediate product of the hydrogen sulfide oxidation. When exponential growth had been achieved, the addition of hydrogen sulfide was terminated leading to elemental sulfur oxidation. The ratio of consumed sulfur to consumed oxygen suggested that sulfuric acid was the ultimate oxidation product. To the knowledge of the authors, this is the first study to determine the growth rate of bacteria involved in concrete corrosion with hydrogen sulfide as source of reduced sulfur.

  12. Experimental study of bond-slip performance of corroded reinforced concrete under cyclic loading

    Directory of Open Access Journals (Sweden)

    Haijun Zhou

    2015-03-01

    Full Text Available Reinforced concrete structures exposed to marine environment often sustain high levels of chloride-induced reinforcement corrosion, which causes reinforcement corrosion and resulting in degraded performance under cyclic service loading. This article studied the dynamic bond performance between corroded reinforcing and concrete under force controlled loading. Tests were carried out to evaluate the cyclic bond-slip degradation with different reinforcement corrosion levels. A series of 30 specimens with various corrosion levels of rebar and stirrup were made. The specimen was cast as concrete cube with the dimension of 200 mm, and a steel rebar was centrally embedded with two stirrups around. The embedded steel rebar and stirrups were corroded using an electrochemical accelerated corrosion technique. The corrosion crack opening width and length were recorded after completion of artificial corrosion. Then, cyclic loading test was carried out; three different force levels of 24, 36, and 48 kN were adopted. The effects of reinforcement corrosion rate on crack opening, maximum slip, energy dissipation, and unloading stiffness were discussed in detail. It was found that both reinforcement corrosion rate and crack opening would have significant effects on cyclic bond performance. Further studies are urgently needed to quantify these effects to the cyclic bond performance.

  13. Nanoscale imaging of alteration layers of corroded international simple glass particles using ToF-SIMS

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jiandong; Neeway, James J.; Zhang, Yanyan; Ryan, Joseph V.; Yuan, Wei; Wang, Tieshan; Zhu, Zihua

    2017-08-01

    Glass particles with dimensions typically ranging from tens to hundreds of microns are often used in glass corrosion research in order to accelerate testing. Two-dimensional and three-dimensional nanoscale imaging techniques are badly needed to characterize the alteration layers at the surfaces of these corroded glass particles. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) can provide a lateral resolution as low as ~100 nm, and, compared to other imaging techniques, is sensitive to elements lighter than carbon. In this work, we used ToF-SIMS to characterize the alteration layers of corroded international simple glass (ISG) particles. At most particle surfaces, inhomogeneous or no alteration layers were observed, indicating that the thickness of the alterations layers may be too thin to be observable by ToF-SIMS imaging. Relatively thick (e.g., 1-10 microns) alteration layers were inhomogeneously distributed at a small portion of surfaces. More interestingly, some large-size (tens of microns) glass particles were fully altered. Above observations suggest that weak attachment and the defects on ISG particle surfaces play an important role in ISG glass corrosion.

  14. Anti-chloride permeability and anti-chloride corrodibility of a green high performance concrete admixture in concrete

    Institute of Scientific and Technical Information of China (English)

    ZHENG Yongbao; LIU Xinrong; LIU Dongyan; CHEN Jiangong; HUANG Xiongjun

    2003-01-01

    The effects of green high performance concrete (GHPC) admixture on the anti-chloride permeability and anti- chloride corrodibility of concrete are studied by a series of experiments designed on the basis of the diffusion principle and electrochemical principle. The GHPC admixture consists of fly ash, gangue, slag, red mud, etc., of which the mass fraction of industrial residues is over 96 %. The anti-permeabilities and anti-corrodibilities of the tested GHPC and normal concrete (NC) are evaluated by the Diffusion Coefficients of chloride which was obtained by measuring the concentration of chloride in the tested systems by the voltage difference method. It is found that the adoption of GHPC admixture greatly improves the anti-chloride permeability and anti-chloride corrodibility by modifying the inner structure and contracting the porosity of concrete to the reduce considerably the diffusion rate of chloride. The admixture is desirable regarding its engineering performances as well as economical and environmental interests.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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...

  20. 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...

  1. 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.

  2. Failure Pressure Analysis of Corroded Moderate-to-High Strength Pipelines

    Institute of Scientific and Technical Information of China (English)

    苏晨亮; 李昕; 周晶

    2016-01-01

    Based on the elastic-plastic, large-deformation finite element method, burst capacity of steel pipeline with longitudinal corrosion defect subjected to internal pressure is studied. The appropriate stress-based criterion is used to predict the failure pressure of finite element model of corroded pipeline under internal pressure. By considering the pipe steel grades and geometries of corrosion defects, a series of finite element analyses is conducted. The effects of corrosion depth, length and width on burst capacity are also discussed. A specific failure pressure solution for the assessment of corrosion defects in moderate-to-high strength pipeline is proposed on the base of numerical results. The failure pressures predicted by the proposed method are in better agreement with the experimental results than the results by the other methods.

  3. Improved removal of arsenic from groundwater using pre-corroded steel and iron tailored granular activated carbon.

    Science.gov (United States)

    Zou, J; Cannon, F S; Chen, W; Dempsey, B A

    2010-01-01

    The authors have combined corrosion of steel fittings or perforated sheets with granular activated carbon (GAC) that had been pre-treated with Fe(III)-citrate, to produce an innovative and low-maintenance technique for removing arsenic from groundwater. Removal of arsenic was measured using two GAC column configurations: rapid small scale column tests (RSSCT's) and mini-column tests. Independent variables included pH, pre-corrosion procedure, and idling of the column (i.e. intentionally stopping flow for defined times in order to create reducing conditions). Use of corroded steel plus pre-treated GAC removed arsenic to below 10 microg/L for up to 248,000 bed volumes (BV) at pH 6, compared to 7,000 BVs for pre-treated GAC without pre-corroded steel. Performance was not as good at pH 6.5 or 7.5. Idling the system recovered the iron corrosion ability by reducing the passive Fe(III) layer on pre-corroded steel surface, as a result the BVs to arsenic breakthrough was doubled. But idling also caused brief periods of arsenic and iron release after restart, due to reductive dissolution of arsenic-containing ferric oxides. GAC was also effective as filtration media for removal of iron (hydr)oxide particles (and associated arsenic) that was released from the pre-corroded iron.

  4. 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.

  5. 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...

  6. A MEMS diamond hemispherical resonator

    Science.gov (United States)

    Bernstein, J. J.; Bancu, M. G.; Cook, E. H.; Chaparala, M. V.; Teynor, W. A.; Weinberg, M. S.

    2013-12-01

    In this paper we report the fabrication of hemispherical polycrystalline diamond resonators fabricated on a novel high-temperature glass substrate. The hemispherical resonator gyroscope is one of the most accurate and rugged of the mechanical gyroscopes, and can be operated in either rate or whole-angle mode due to its high degree of symmetry. A fabrication sequence for creating extremely symmetric 3D MEMS hemispheres is presented. Mode shapes and frequencies obtained with a laser vibrometer are shown, as well as curves of Q versus pressure, and the dependence of frequency on anchor size. Fundamental mode frequency matching to gyroscope operation in whole-angle mode.

  7. 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.

  8. Brain Hemispheres and Thinking Styles.

    Science.gov (United States)

    Gray, Esther Cappon

    1980-01-01

    The author reviews some research, particularly that of Roger Sperry, substantiating the existence of different thinking styles in the two brain hemispheres and the development of this differentiation in infancy and childhood. She draws some implications for elementary teaching. (SJL)

  9. 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

  10. 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.

  11. 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.

  12. Western Hemisphere Knowledge Partnerships

    Science.gov (United States)

    Malone, T. F.

    2001-05-01

    , and application of knowledge concerning the nature of -- and interaction among -- matter, living organisms, energy, information, and human behavior. This strategy calls for innovative partnerships among the physical, biological, health, and social sciences, engineering, and the humanities. New kinds of partnership must also be forged among academia, business and industry, governments, and nongovernmental organizations. Geophysicists can play an important role in these partnerships. A focus for these partnerships is to manage the individual economic productivity that drives both human development and global change. As world population approaches stability during the twenty-first century, individual economic productivity will be the critical link between the human and the natural systems on planet Earth. AGU is among a core group of individuals and institutions proposing Western Hemisphere Knowledge Partnerships (WHKP) to test the hypothesis that knowledge, broadly construed, is an important organizing principle in choosing a path into the future. The WHKP agenda includes: (1) life-long learning, (2) the health and resilience of natural ecosystems, (3) eco-efficiency in economic production and consumption, (4) extension of national income accounts, (5) environmentally benign sources of energy, (6) delivery of health care, (7) intellectual property rights, and (8) networks for action by local communities.Collaboratories and distance education technologies will be major tools. A panel of experts will explore this proposal.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. Finite Element Method Analysis of the Stress for Line Pipe with Corrode Groove During Outdoor Storage

    Institute of Scientific and Technical Information of China (English)

    Zhuanzhao YANG; Daoxin LIU; Xiaohua ZHANG

    2013-01-01

    The basic principle of corrode groove on outside of steel pipe during storage was analyzed in this paper,namely the water film on the contacted surface of steel pipe,which gathered from humidity in the air,rain or gel,and the suspended particles in air,and the corrosive composition,such as SO2,CO2,O2 and NaCl,in addition to the inhomogeneity of the organization and composition,which lead to the corrosion cell reaction,so that cause the corrosion initial from the contact surface of the between steel pipes,so as to form the corrosion groove.At the same time,the corrosion groove with depth of 0.125t (t pipe wall thickness) on the pipe of φ 1016 mm×21 mm X70 API SPEC 5L was simulated using the FEM (finite element method),and the stress and strain distribution of the defect area near corrosion groove were solved at the inner pressure of 12 MPa,10 MPa,8 MPa,6 MPa,4 MPa and 2 MPa,respectively,which showed that no matter the pressure values were,the maximum stress and strain were lied at the bottom of corrosion defects groove and were in good linear relationship with the internal pressure increasing from 2 MPa to 6 MPa.When the internal pressures were greater than 6 MPa,they felled into the nonlinear model and to be yielded or even to be destroyed.In addition,the residual strength and the limit operation pressure of the corrode pipe with the defects groove of 0.125t were calculated or simulated according to the theoretical calculation,the finite element method based on the stress,the finite element method based on strain,DNV-RP-F101,ASME B31G and experimental methods respectively.The results showed that the residual strength and the limit operation pressure of the defective parts solved by the finite element method based on stress were 424 MPa,and 15.34 MPa,respectively,which was very close to that of experimental method,the residual strength was 410 MPa and the limit operation pressure 14.78 MPa.Besides,the results also showed that it was feasible and effective to

  18. Isolation of iron-oxidizing bacteria from corroded concretes of sewage treatment plants.

    Science.gov (United States)

    Maeda, T; Negishi, A; Komoto, H; Oshima, Y; Kamimura, K; Sugio, T

    1999-01-01

    Thirty-six strains of iron-oxidizing bacteria were isolated from corroded concrete samples obtained at eight sewage treatment plants in Japan. All of the strains isolated grew autotrophically in ferrous sulfate (3.0%), elemental sulfur (1.0%) and FeS (1.0%) media (pH 1.5). Washed intact cells of the 36 isolates had activities to oxidize both ferrous iron and elemental sulfur. Strain SNA-5, a representative of the isolated strains, was a gram-negative, rod-shaped bacterium (0.5-0.6x0.9-1.5 microm). The mean G+C content of its DNA was 55.9 mol%. The pH and temperature optima for growth were 1.5 and 30 degrees C, and the bacterium had activity to assimilate 14CO2 into the cells when ferrous iron or elemental sulfur was used as a sole source of energy. These results suggest that SNA-5 is Thiobacillus ferrooxidans strain. The pHs and numbers of iron-oxidizing bacteria in corroded concrete samples obtained by boring to depths of 0-1, 1-3, and 3-5 cm below the concrete surface were respectively 1.4, 1.7, and 2.0, and 1.2 x 10(8), 5 x 10(7), and 5 x 10(6) cells/g concrete. The degree of corrosion in the sample obtained nearest to the surface was more severe than in the deeper samples. The findings indicated that the levels of acidification and corrosion of the concrete structure corresponded with the number of iron-oxidizing bacteria in a concrete sample. Sulfuric acid produced by the chemolithoautotrophic sulfur-oxidizing bacterium Thiobacillus thiooxidansis known to induce concrete corrosion. Since not only T. thiooxidans but also T. ferrooxidans can oxidize reduced sulfur compounds and produce sulfuric acid, the results strongly suggest that T. ferrooxidans as well as T. thiooxidans is involved in concrete corrosion.

  19. 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.

  20. 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.

  1. 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.

  2. Considerations on the repassivation of corroded reinforced concrete structures; Consideraciones sobre la repasivacion de las estructuras corroidas de hormigon armado

    Energy Technology Data Exchange (ETDEWEB)

    Cobo, A.; Gonzalez, M. N. [Escuela Universitaria de Arquitectura Tecnica de Madrid. Madrid (Spain); Otero, E.; Gonzalez, J. A. [Centro Nacional de Investigaciones Metalurgicas. CENIM. Madrid (Spain)

    2000-07-01

    An analysis is made of the responses of clean and precorroded steel electrodes in Ca(OH){sub 2} saturated solutions and in cement mortar, using gravimetric, metallographic and electrochemical techniques, essentially polarisation resistance measurements. The paper aims to answer some important questions about the corrosion of reinforced concrete structures (RCS) which, though seemingly elementary, continue to arouse controversy in scientific, technical and economical circles, such as the following: What corrosion rates are dangerous in RCS? What concrete resistivities guarantee sufficient durability of RCS?. Is it possible to detain corrosion once it has begun?. Can corroded RCS be repassivated? Are electrochemical RCS rehabilitation methods efficient, and if so, when? The results obtained indicate that electrochemical chloride removal and realkalisation cannot repassive heavily corroded steel surfaces, however they can be effective methods to prevent corrosion provided they are used before the transition from the passive state to the active one occurs. If applied to late, are useless for this purpose. (Author) 25 refs.

  3. 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.

  4. Performance of Strengthened Non-Uniformly Corroded Reinforced SCC-RAP Members

    Directory of Open Access Journals (Sweden)

    Ahmed Abdel-Mohti

    2016-12-01

    Full Text Available This research examines the performance of strengthened non-uniformly corroded reinforced self-consolidating concrete (SCC members. This paper focuses on three aspects of concrete including corrosion, concrete cover loss, and repair technique. Up to a 50% corrosion level is considered in this study. Corrosion was experimentally induced and was simulated in other cases. Twenty-six reinforced concrete (RC members with various corrosion levels or simulated corrosion levels were constructed and investigated. The beams with corrosion problems including those that had experimentally induced corrosion or simulated corrosion, with or without concrete cover, were repaired using carbon fiber reinforced polymer (CFRP sheets and U-wraps. Two line loads were applied to all of the non-repaired and repaired beams constructed in this study until failure. It was found that it is conservative to model the actual corrosion by simulating the equivalent area of steel reinforcing for up to a 20% level of corrosion. For corrosion levels over 20%, the simulated corrosion over predicts the load capacity of the actual corrosion cases. When the concrete cover was lost and for a corrosion level larger than 10%, the repaired beam did not reach similar performance to that of a repaired beam with a concrete cover that was still intact. It appears that using two layers of CFRP sheet did not improve the load capacity further, but rather improved the ductility of the deteriorated RC member.

  5. Comparison of friction force between corroded and noncorroded titanium nitride plating of metal brackets.

    Science.gov (United States)

    Kao, Chia-Tze; Guo, Jia-Uei; Huang, Tsui-Hsien

    2011-05-01

    Titanium nitride (TiN) plating is a method to prevent metal corrosion and can increase the surface smoothness. The purpose of this study was to evaluate the friction forces between the orthodontic bracket, with or without TiN plating, and stainless steel wire after it was corroded in fluoride-containing solution. In total, 540 metal brackets were divided into a control group and a TiN-coated experimental group. The electrochemical corrosion was performed in artificial saliva with 1.23% acidulated phosphate fluoride (APF) as the electrolytes. Static and kinetic friction were measured by an EZ-test machine (Shimadazu, Tokyo, Japan) with a crosshead speed of 10 mm per minute over a 5-mm stretch of stainless steel archwire. The data were analyzed by using unpaired t test and analysis of variance (ANOVA). Both the control and TiN-coated groups' corrosion potential was higher with 1.23% APF solution than with artificial solution (P TiN-coated brackets groups showed a statistically significant difference (P TiN-coated brackets showed a statistical difference (P TiN-coated metal brackets, with corrosion or without corrosion, cannot reduce the frictional force. Copyright © 2011 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  6. Surface layers on a borosilicate nuclear waste glass corroded in MgCl 2 solution

    Science.gov (United States)

    Abdelouas, Abdesselam; Crovisier, Jean-Louis; Lutze, Werner; Grambow, Bernd; Dran, Jean-Claude; Müller, Regina

    1997-01-01

    Surface layers on the French borosilicate nuclear waste glass, R7T7, corroded in MgCl 2 solution were studied to determine the composition, structure and stability of crystalline phases. The characteristics of the phases constituting the surface layer varied with the parameter {S}/{V} × t , the glass surface area ( S) to solution volume ( V) ratio, times time ( t). At low {S}/{V} × t values (intermediate {S}/{V} × t value (2800 d/m; 5.5 y) the surface layer contained hydrotalcite-, chlorite- and saponite-type phases. At the highest {S}/{V} × t value (10 7 d/m; 463 d) the major phases were saponite, powellite, barite and cerianite solid solutions. About 95% of the uranium and > 98% of the neodymium released from the glass were precipitated in the surface layer. In the 463 day experiment, 86% of the neodymium in the surface layer was in solid solution with powellite, the rest with saponite. Uranium was contained exclusively in saponite. High {S}/{V} ratios, typical of disposal conditions for vitrified high-level radioactive waste, favor retention of actinides in fairly insoluble corrosion products. Observation of similar corrosion products on natural glasses as on nuclear waste glasses lend support to the hypothesis that the host phases for actinides observed in the laboratory are stable over geological periods of time.

  7. A Study on the Bond Behavior of Corroded Reinforced Concrete Containing Recycled Aggregates

    Directory of Open Access Journals (Sweden)

    Haifeng Yang

    2015-01-01

    Full Text Available This paper investigated bond-slip characteristics of chloride-induced corroded reinforced concrete incorporating different levels of recycled concrete aggregates (RCA. Pullout tests were adopted to evaluate the bonding and debonding behaviors of the embedded rebar experiencing different corrosion levels. Both high- and low-strength concrete were considered. Bond-slip curves were recorded to determine the influences of rebar corrosion levels and RCA replacements on the bond strength and debonding energy of the specimens. Test results indicate that increasing rebar corrosion level gradually weakens the antisliding ability of reinforced recycled aggregate concrete (RAC except for a small level corrosion and the degradation rate of ultimate bond strength increases with a decrease of compressive strength at 0.5% rebar corrosion. The results also demonstrate that the ultimate bond strength of reinforced RAC slightly decreases with an increase of RCA replacement. However, the relative bond strength between uncorroded rebar and RAC is little affected by RCA content, while it decreases with an increase of RCA replacement in high-strength specimens after rebar corrosion. The debonding energy between deformed rebar and RAC is found decreasing with the increment of the rebar corrosion level and increasing with an increase of RAC content.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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

  14. Effects of Corroded and Non-Corroded Biodegradable Mg and Mg Alloys on Viability, Morphology and Differentiation of MC3T3-E1 Cells Elicited by Direct Cell/Material Interaction.

    Directory of Open Access Journals (Sweden)

    Sepideh Mostofi

    Full Text Available This study investigated the effect of biodegradable Mg and Mg alloys on selected properties of MC3T3-E1 cells elicited by direct cell/material interaction. The chemical composition and morphology of the surface of Mg and Mg based alloys (Mg2Ag and Mg10Gd were analysed by scanning electron microscopy (SEM and EDX, following corrosion in cell culture medium for 1, 2, 3 and 8 days. The most pronounced difference in surface morphology, namely crystal formation, was observed when Pure Mg and Mg2Ag were immersed in cell medium for 8 days, and was associated with an increase in atomic % of oxygen and a decrease of surface calcium and phosphorous. Crystal formation on the surface of Mg10Gd was, in contrast, negligible at all time points. Time-dependent changes in oxygen, calcium and phosphorous surface content were furthermore not observed for Mg10Gd. MC3T3-E1 cell viability was reduced by culture on the surfaces of corroded Mg, Mg2Ag and Mg10Gd in a corrosion time-independent manner. Cells did not survive when cultured on 3 day pre-corroded Pure Mg and Mg2Ag, indicating crystal formation to be particular detrimental in this regard. Cell viability was not affected when cells were cultured on non-corroded Mg and Mg alloys for up to 12 days. These results suggest that corrosion associated changes in surface morphology and chemical composition significantly hamper cell viability and, thus, that non-corroded surfaces are more conducive to cell survival. An analysis of the differentiation potential of MC3T3-E1 cells cultured on non-corroded samples based on measurement of Collagen I and Runx2 expression, revealed a down-regulation of these markers within the first 6 days following cell seeding on all samples, despite persistent survival and proliferation. Cells cultured on Mg10Gd, however, exhibited a pronounced upregulation of collagen I and Runx2 between days 8 and 12, indicating an enhancement of osteointegration by this alloy that could be valuable for

  15. The effect of chloride ions on the corroded surface layer of 00Cr22Ni5Mo3N duplex stainless steel under cavitation.

    Science.gov (United States)

    Wan, Tong; Xiao, Ning; Shen, Hanjie; Yong, Xingyue

    2016-11-01

    The effects of Cl(-) on the corroded surface layer of 00Cr22Ni5Mo3N duplex stainless steel under cavitation in chloride solutions were investigated using nanoindentation in conjunction with XRD and XPS. The results demonstrate that Cl(-) had a strong effect on the nano-mechanical properties of the corroded surface layer under cavitation, and there was a threshold Cl(-) concentration. Furthermore, a close relationship between the nano-mechanical properties and the cavitation corrosion resistance of 00Cr22Ni5Mo3N duplex stainless steel was observed. The degradation of the nano-mechanical properties of the corroded surface layer was accelerated by the synergistic effect between cavitation erosion and corrosion. A key factor was the adsorption of Cl(-), which caused a preferential dissolution of the ferrous oxides in the passive film layer on the corroded surface layer. Cavitation further promoted the preferential dissolution of the ferrous oxides in the passive film layer. Simultaneously, cavitation accelerated the erosion of the ferrite in the corroded surface layer, resulting in the degradation of the nano-mechanical properties of the corroded surface layer on 00Cr22Ni5Mo3N duplex stainless steel under cavitation.

  16. Hemispheric specialisation in haptic processing.

    Science.gov (United States)

    Tomlinson, Simon P; Davis, Nick J; Morgan, Helen M; Bracewell, R Martyn

    2011-07-01

    This study investigated the organising principles of touch. We examined specialisations within the haptic system and their hemispheric distribution. Haptic processing consists of the integration of data from multiple sources to form a single percept. Previous research provides strong support for a hierarchical and functional distribution within haptic processing. We investigated hemispheric asymmetry in haptic discrimination of objects with differing textures and centres of mass. By analogy with vision it was hypothesised that participants would demonstrate a left-hand advantage for centre of mass discrimination (a 'global', presumed right hemisphere, judgement) and a right-hand advantage for surface texture judgements (a 'local', presumed left hemisphere discrimination). We found that left-handed participants showed these effects to a lesser degree than did the right-handers, consistent with the notion that left-handed people generally show weaker asymmetries in bimanual tasks. In a second experiment the effect of conflicting information on haptic percept formation was investigated. Following from the previous hypotheses it was predicted that participants would be more accurate with their right hands at judging conflicting surfaces. Contrary to predictions an advantage was demonstrated for the left hand for texture discrimination and for the right hand for centre of mass judgement.

  17. 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.

  18. 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 ...

  19. 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.

  20. 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...

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. Fusibacter bizertensis sp. nov., isolated from a corroded kerosene storage tank.

    Science.gov (United States)

    Smii, Latifa; Ben Hania, Wajdi; Cayol, Jean-Luc; Joseph, Manon; Hamdi, Moktar; Ollivier, Bernard; Fardeau, Marie-Laure

    2015-01-01

    Strain LTF Kr01(T), a novel mesophilic, anaerobic, halotolerant, rod-shaped bacterium, was isolated from a drain at the bottom of a corroded kerosene storage tank of the Société Tunisienne des Industries de Raffinage (STIR), Bizerte, northern Tunisia. Cells were Gram-positive-staining rods, occurred singly or in pairs, and were motile by one lateral flagellum. Strain LTF Kr01(T) grew at temperatures between 15 and 40 °C (optimum 30 °C), between pH 5.5 and 8.2 (optimum pH 7.2) and at NaCl concentrations between 0 and 50 g l(-1) (optimum 5 g l(-1)). It reduced thiosulfate and elemental sulfur into sulfide, but did not reduce sulfate or sulfite. It utilized a wide range of carbohydrates (cellobiose, d-glucose, d-fructose, d-mannitol, d-ribose, sucrose, d-xylose, maltose, d-galactose, starch and trehalose) and produced acetate, CO2 and H2 as end products from glucose fermentation. The DNA G+C content was 37.4 mol%. The predominant cellular fatty acids were C14:0 and C16:0. Phylogenetic analysis of the 16S rRNA gene sequence suggested that Fusibacter tunisiensis was the closest relative of strain LTF Kr01(T) (gene sequence similarity of 94.6%). Based on phenotypic, phylogenetic and genotypic taxonomic characteristics, strain LTF Kr01(T) is proposed to represent a novel species of the genus Fusibacter, order Clostridiales, for which the name Fusibacter bizertensis sp. nov. is proposed. The type strain is LTF Kr01(T) ( = DSM 28034(T) = JCM 19376(T)). © 2015 IUMS.

  7. Relationship between defect shape resolution accuracy and calculated remaining strength of corroded pipelines

    Energy Technology Data Exchange (ETDEWEB)

    Grant, R.; Chauhan, V. [Advantica Ltd., Loughborough (United Kingdom); Sloterdijk, W. [Gastransport Services, Gronigen (Netherlands)

    2004-07-01

    This paper provided details of research investigating the interactions of corrosion metal loss features detected using in-line inspection (ILI) tool. The study examined the potential benefits of using more detailed information concerning the shape of metal loss features in conjunction with defect assessment methods. The effects of varying assumptions made in the criteria used to determine the interaction of closely spaced defect clusters were also investigated. High resolution magnetic flux leakage (MFL) data containing a large proportion of metal loss features was used in a series of sensitivity studies. Automated assessments were undertaken using the RSTRENG method by varying defect dimensions and the interaction criterion. The sensitivity studies to predict failure pressures were undertaken by increasing the reported defect depths by increments of 5, 10, and 20 per cent of the wall thickness. Length and width measurements remained at their reported values. A further set of sensitivity studies was then conducted to predict failure pressures by varying the defect length by an additional 5 mm and 10 mm. Results of the study showed that an accurate knowledge of the defect depth, followed by defect length was of the most benefit in determining the remaining strength of corroded pipelines. It was concluded that by increasing the defect depth measurement accuracy of MFL tools will result in a linear increase in predicted failure pressures. The sensitivity studies showed that the assumptions made in relation to interaction criterion used to decide if defects are clustered together may play a significant role in defect assessments. 17 refs., 2 tabs., 4 figs.

  8. Metagenome analyses of corroded concrete wastewater pipe biofilms reveal a complex microbial system

    Directory of Open Access Journals (Sweden)

    Gomez-Alvarez Vicente

    2012-06-01

    Full Text Available Abstract Background Concrete corrosion of wastewater collection systems is a significant cause of deterioration and premature collapse. Failure to adequately address the deteriorating infrastructure networks threatens our environment, public health, and safety. Analysis of whole-metagenome pyrosequencing data and 16S rRNA gene clone libraries was used to determine microbial composition and functional genes associated with biomass harvested from crown (top and invert (bottom sections of a corroded wastewater pipe. Results Taxonomic and functional analysis demonstrated that approximately 90% of the total diversity was associated with the phyla Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria. The top (TP and bottom pipe (BP communities were different in composition, with some of the differences attributed to the abundance of sulfide-oxidizing and sulfate-reducing bacteria. Additionally, human fecal bacteria were more abundant in the BP communities. Among the functional categories, proteins involved in sulfur and nitrogen metabolism showed the most significant differences between biofilms. There was also an enrichment of genes associated with heavy metal resistance, virulence (protein secretion systems and stress response in the TP biofilm, while a higher number of genes related to motility and chemotaxis were identified in the BP biofilm. Both biofilms contain a high number of genes associated with resistance to antibiotics and toxic compounds subsystems. Conclusions The function potential of wastewater biofilms was highly diverse with level of COG diversity similar to that described for soil. On the basis of the metagenomic data, some factors that may contribute to niche differentiation were pH, aerobic conditions and availability of substrate, such as nitrogen and sulfur. The results from this study will help us better understand the genetic network and functional capability of microbial members of wastewater concrete biofilms.

  9. 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.

  10. Hypnosis in the right hemisphere.

    Science.gov (United States)

    Kihlstrom, John F; Glisky, Martha L; McGovern, Susan; Rapcsak, Steven Z; Mennemeier, Mark S

    2013-02-01

    Speculations about the neural substrates of hypnosis have often focused on the right hemisphere (RH), implying that RH damage should impair hypnotic responsiveness more than left-hemisphere (LH) damage. The present study examined the performance of a patient who suffered a stroke destroying most of his LH, on slightly modified versions of two hypnotizability scales. This patient was at least modestly hypnotizable, as indicated in particular by the arm rigidity and age regression items, suggesting that hypnosis can be mediated by the RH alone - provided that the language capacities normally found in the LH remain available. A further study of 16 patients with unilateral strokes of the LH or RH found no substantial differences in hypnotizability between the two groups. Future neuropsychological studies of hypnosis might explore the dorsal/ventral or anterior/posterior dichotomies, with special emphasis on the role of prefrontal cortex. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Hemispheric ultra-wideband antenna.

    Energy Technology Data Exchange (ETDEWEB)

    Brocato, Robert Wesley

    2006-04-01

    This report begins with a review of reduced size ultra-wideband (UWB) antennas and the peculiar problems that arise when building a UWB antenna. It then gives a description of a new type of UWB antenna that resolves these problems. This antenna, dubbed the hemispheric conical antenna, is similar to a conventional conical antenna in that it uses the same inverted conical conductor over a ground plane, but it also uses a hemispheric dielectric fill in between the conductive cone and the ground plane. The dielectric material creates a fundamentally new antenna which is reduced in size and much more rugged than a standard UWB conical antenna. The creation of finite-difference time domain (FDTD) software tools in spherical coordinates, as described in SAND2004-6577, enabled this technological advance.

  12. Western Hemisphere Defense Policy Statement

    Science.gov (United States)

    2012-10-01

    El Salvador, Guatemala, Honduras , Paraguay, Peru and Uruguay have contributed to or led multi-national security operations and United Nations (UN...impact on regional and global peace and security and reflect the new realities of defense cooperation in the hemisphere. Working with Canada and...Mexico, DoD remains prepared to deter and defeat direct threats to our homeland. We partner with Canada on regional security issues such as an evolving

  13. Hemispheric Laterality in Music and Math

    Science.gov (United States)

    Szirony, Gary Michael; Burgin, John S.; Pearson, L. Carolyn

    2008-01-01

    Hemispheric laterality may be a useful concept in teaching, learning, training, and in understanding more about human development. To address this issue, a measure of hemispheric laterality was compared to musical and mathematical ability. The Human Information Processing Survey (HIPS) instrument, designed to measure hemispheric laterality, was…

  14. Right Hemisphere Dominance in Visual Statistical Learning

    Science.gov (United States)

    Roser, Matthew E.; Fiser, Jozsef; Aslin, Richard N.; Gazzaniga, Michael S.

    2011-01-01

    Several studies report a right hemisphere advantage for visuospatial integration and a left hemisphere advantage for inferring conceptual knowledge from patterns of covariation. The present study examined hemispheric asymmetry in the implicit learning of new visual feature combinations. A split-brain patient and normal control participants viewed…

  15. Brain Hemispheric Functions and the Native American.

    Science.gov (United States)

    Ross, Allen Chuck

    1982-01-01

    Uses brain research conducted by Dr. Roger Sperry to show that traditional Native Americans are more dominant in right hemisphere thinking, setting them apart from a modern left hemisphere-oriented society (especially emphasized in schools). Describes some characteristics of Native American thinking that illustrate a right hemisphere orientation…

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. Non-contact Measurement of Remaining Thickness of Corroding Superheater Tubes. Phase 2

    Energy Technology Data Exchange (ETDEWEB)

    Borggreen, Kjeld; Storesund, Jan

    2007-12-15

    The Electro Magnetic Acoustic Transducer (EMAT) is a contactless thickness gauge for detection of corrosion on superheater tubes; it candidates as substitute for conventional manually operated contact UT transducers. It is the aim of the project to demonstrate the usefulness of two simple EMAT systems, Panametrics and Sonatest, for fast and reliable tube thickness inspections in difficult-to-access superheater sections. The present Phase 2 of the project involves testing of the systems on real compact superheaters in remote operation with the help of a mechanical manipulator designed and built for the purpose. The results are the following: - Both EMAT systems work well when tested in the field during handheld operation on tubes with a moderate thick layer of corrosion products and ash. The practical obtainable speed of cross-panel inspection of easily accessible panels is approximately 6 tubes per minute (6 thickness readings per minute). - The Sonatest system works well when tested in the field during remote operation on heavily corroded superheater tubes with thick ash layer. The Panametrics system was not found suitable for this type of field work. - The mechanical manipulator works well for cross-panel inspection of difficult-to-access superheater sections independent of the tube dimensions and the free space between the panels. In its present design it needs few improvements. - The practical obtainable speed of cross-panel inspection is 3 tubes per minute (3 thickness readings per minute). This speed is limited by the detection rate of the EMAT system and not by the travelling speed of the probe. - Scanning of tubes along their axis was never attempted, because the EMAT instruments were not capable of collecting data coming as a continuous stream. - It cannot be judged from visual alone and hardly from the service data, if a tube or a panel can be inspected by the magnetostrictive EMAT method or not. - The main contribution to failure of the EMAT inspection

  2. Na{sub 2}PO{sub 3}F as inhibitor of corroding reinforcement in carbonated concrete

    Energy Technology Data Exchange (ETDEWEB)

    Alonso, C.; Andrade, C.; Argiz, C. [Inst. of Construction Science Eduardo Torroja, Madrid (Spain); Malric, B. [Locher and Co., Geneva (Switzerland)

    1996-03-01

    In the present paper a protective action of Na{sub 2}PO{sub 3}F from corrosion of steel concrete in carbonated environments is presented. The inhibitor effect has been followed using electrochemical techniques. Na{sub 2}PO{sub 3}F has been tested as a curative method penetrating from outside when the steel reinforcement is already corroding by carbonation of concrete cover. Results show that the product can reduce significantly an active corrosion through the use of drying and wetting cycles of the concrete cover with solutions having high concentration of Na{sub 2}PO{sub 3}F.

  3. Succession of Sulfur-Oxidizing Bacteria in the Microbial Community on Corroding Concrete in Sewer Systems† ▿

    Science.gov (United States)

    Okabe, Satoshi; Odagiri, Mitsunori; Ito, Tsukasa; Satoh, Hisashi

    2007-01-01

    Microbially induced concrete corrosion (MICC) in sewer systems has been a serious problem for a long time. A better understanding of the succession of microbial community members responsible for the production of sulfuric acid is essential for the efficient control of MICC. In this study, the succession of sulfur-oxidizing bacteria (SOB) in the bacterial community on corroding concrete in a sewer system in situ was investigated over 1 year by culture-independent 16S rRNA gene-based molecular techniques. Results revealed that at least six phylotypes of SOB species were involved in the MICC process, and the predominant SOB species shifted in the following order: Thiothrix sp., Thiobacillus plumbophilus, Thiomonas intermedia, Halothiobacillus neapolitanus, Acidiphilium acidophilum, and Acidithiobacillus thiooxidans. A. thiooxidans, a hyperacidophilic SOB, was the most dominant (accounting for 70% of EUB338-mixed probe-hybridized cells) in the heavily corroded concrete after 1 year. This succession of SOB species could be dependent on the pH of the concrete surface as well as on trophic properties (e.g., autotrophic or mixotrophic) and on the ability of the SOB to utilize different sulfur compounds (e.g., H2S, S0, and S2O32−). In addition, diverse heterotrophic bacterial species (e.g., halo-tolerant, neutrophilic, and acidophilic bacteria) were associated with these SOB. The microbial succession of these microorganisms was involved in the colonization of the concrete and the production of sulfuric acid. Furthermore, the vertical distribution of microbial community members revealed that A. thiooxidans was the most dominant throughout the heavily corroded concrete (gypsum) layer and that A. thiooxidans was most abundant at the highest surface (1.5-mm) layer and decreased logarithmically with depth because of oxygen and H2S transport limitations. This suggested that the production of sulfuric acid by A. thiooxidans occurred mainly on the concrete surface and the

  4. Succession of Sulfur-Oxidizing Bacteria in the Microbial Community on Corroding Concrete in Sewer Systems† ▿

    OpenAIRE

    Okabe, Satoshi; Odagiri, Mitsunori; Ito, Tsukasa; Satoh, Hisashi

    2007-01-01

    Microbially induced concrete corrosion (MICC) in sewer systems has been a serious problem for a long time. A better understanding of the succession of microbial community members responsible for the production of sulfuric acid is essential for the efficient control of MICC. In this study, the succession of sulfur-oxidizing bacteria (SOB) in the bacterial community on corroding concrete in a sewer system in situ was investigated over 1 year by culture-independent 16S rRNA gene-based molecular ...

  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. 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 ...

  7. 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.

  8. 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.

  9. 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.

  10. 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...

  11. 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.

  12. 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...

  13. 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...

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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...

  19. 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.

  20. 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.

  1. 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...

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. LEO 1.0. An assistant software for maintenance of corroded reinforced concrete structures; LEO 1.0. Logiciel d`aide l`expertise des ouvrages en beton arme corrodes

    Energy Technology Data Exchange (ETDEWEB)

    Gerard, B.; Petre-Lazar, I

    1998-04-01

    The reinforced concrete structures capacity to fulfill the users requirements decreases in time and a constant preoccupation for the maintenance is required at EDF. In order to ease up the site investigations, a computer program - LEO - is developed. Its general layout is proposed in this document. LEO 1.0 is developed to be applied to corroded reinforced concrete structures. A simplified model based on the main mechanisms of the steel corrosion in concrete has been developed. It can quantify the influence of the reinforcement corrosion on the structure performances. A probabilistic calculus which takes into account the variability of the input data (material properties, environment, etc.) was also performed using PROBAN computer code. This type of analysis quantifies the time evolution of the structure (incubation, initiation, propagation, collapse). (author) 9 refs.

  8. Electroformation of uranium hemispherical shells

    Energy Technology Data Exchange (ETDEWEB)

    Marshall, S.L.; Redey, L.; Vandegrift, G.F.; Vissers, D.R.

    1989-11-01

    This effort was directed at developing an electrochemical process for forming uniform and dendrite-free deposits of uranium from molten salts. This process is to be used for the electroformation of free-standing hemispherical shells of uranium for nuclear applications. Electrodeposition of uranium onto a substrate was accomplished with a fused chloride mixture containing 42 wt% UCl{sub 3} and a fused chloride-fluoride mixture containing 4 wt % UF{sub 4}. Under pulsed potential control at 504{degree}C, the chloride-fluoride mixture yielded the widest range of plating conditions for which dendrites could be avoided. Bipolar current pulse plating with both electrolytes gave good results, and successful application of this technique to a large tubular cathode has been demonstrated. 24 refs., 10 figs.

  9. Hemispheric asymmetries: The comparative view

    Directory of Open Access Journals (Sweden)

    Sebastian eOcklenburg

    2012-01-01

    Full Text Available Hemispheric asymmetries play an important role in almost all cognitive functions. For more than a century, they were considered to be uniquely human but now an increasing number of findings in all vertebrate classes make it likely that we inherited our asymmetries from common ancestors. Thus, studying animal models could provide unique insights into the mechanisms of lateralization. We outline three such avenues of research by providing an overview of experiments on left-right differences in the connectivity of sensory systems, the embryonic determinants of brain asymmetries, and the genetics of lateralization. All these lines of studies could provide a wealth of insights into our own asymmetries that should and will be exploited by future analyses.

  10. Behaviour of corroded steel in a Ca(OH2-saturated solution and in cement mortar. Possibility of rehabilitation

    Directory of Open Access Journals (Sweden)

    Hernández, L. S.

    2007-03-01

    Full Text Available The present study compared the response of rust-free and corroded steel electrodes in Ca(OH2-saturated solutions and in cement mortar, essentially defined in terms of polarization resistance as measured with gravimetric, metallographic and electrochemical methods. Answers were sought for the following questions, which persist despite the use of reinforced concrete (RC in building for over a century: At what corrosion rate is RC durability seriously compromised? Does restoration of the initial conditions in properly manufactured concrete guarantee repassivation of corroded steel? Does the use of inhibitors enhance repassivation? Does the nature of the corrosion products have any significant effect on the response of corroded steel reinforcement? The results obtained in indicated that the effectiveness of preventive methods is much more closely related to the degree of existing corrosion than to the nature of the corrosion products.En el presente trabajo se analizan las respuestas de electrodos de acero, limpios y precorroídos, en soluciones saturadas de Ca(OH2 y en mortero de cemento, recurriendo para ello a técnicas gravimétricas, metalográficas y electroquímicas, esencialmente a medidas de resistencia de polarización. Se intenta encontrar respuesta a las siguientes dudas persistentes después de más de un siglo de utilización de las estructuras de hormigón armado (EHA: ¿qué velocidades de corrosión comprometen seriamente la durabilidad de las EHA? ¿La restauración de las condiciones iniciales de un hormigón correctamente fabricado garantiza la recuperación del estado pasivo en los refuerzos ya corroídos? ¿La utilización de inhibidores facilita la repasivación de los refuerzos? ¿Cambia la naturaleza de los productos de corrosión sustancialmente la respuesta de las armaduras ya corroídas? Los resultados obtenidos indican que la eficacia de las medidas preventivas resulta mucho más condicionada por el grado de

  11. 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...

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. 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

  3. Direct observation of hydration of TiO 2 on Ti using electrochemical AFM: freely corroding versus potentiostatically held

    Science.gov (United States)

    Bearinger, Jane P.; Orme, Christine A.; Gilbert, Jeremy L.

    2001-10-01

    Hydration of titanium/titanium oxide surfaces under freely corroding and potentiostatically held conditions has been characterized using electrochemical atomic force microscopy (EC AFM). In contrast to conventional high vacuum techniques, AFM enables measurement of morphological surface structure in the in situ hydrated state. Electrochemical probes in the imaging environment further enable acquisition of electrical characteristics during AFM imaging. Experiments were performed on etched, electropolished commercially pure titanium. As noted by direct observation and corroborated by power spectral density (Fourier analysis) measurements, oxide domes cover the titanium surface and grow laterally during hydration. Applied potential altered the growth rate. Under open circuit potential conditions, growth proceeded approximately six times faster than under a -1 V applied voltage ( 1098±52 nm2/ min ± versus 184.84±19 nm2/min). Film growth increased electrical resistance and lowered interfacial capacitance based on step polarization impedance spectroscopy tests.

  4. 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.

  5. 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.

  6. 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

  7. Hemispheric Division of Labour in Reading

    Science.gov (United States)

    Shillcock, Richard C.; McDonald, Scott A.

    2005-01-01

    We argue that the reading of words and text is fundamentally conditioned by the splitting of the fovea and the hemispheric division of the brain, and, furthermore, that the equitable division of labour between the hemispheres is a characteristic of normal visual word recognition. We report analyses of a representative corpus of the eye fixations…

  8. The Cost of Action Miscues: Hemispheric Asymmetries

    Science.gov (United States)

    Shenal, Brian V.; Hinze, Stephan; Heilman, Kenneth M.

    2012-01-01

    Adaptive behaviors require preparation and when necessary inhibition or alteration of actions. The right hemisphere has been posited to be dominant for preparatory motor activation. This experiment was designed to learn if there are hemispheric asymmetries in the control of altered plans of actions. Cues, both valid and invalid, which indicate the…

  9. The Cost of Action Miscues: Hemispheric Asymmetries

    Science.gov (United States)

    Shenal, Brian V.; Hinze, Stephan; Heilman, Kenneth M.

    2012-01-01

    Adaptive behaviors require preparation and when necessary inhibition or alteration of actions. The right hemisphere has been posited to be dominant for preparatory motor activation. This experiment was designed to learn if there are hemispheric asymmetries in the control of altered plans of actions. Cues, both valid and invalid, which indicate the…

  10. 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

  11. 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.

  12. 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.

  13. HEMISPHERIC CENTER FOR ENVIRONMENTAL TECHNOLOGY

    Energy Technology Data Exchange (ETDEWEB)

    M.A. Ebadian

    1999-10-31

    The Deactivation and Decommissioning (D&D) Technology Assessment Program (TAP) was developed to provide detailed, comparable data for environmental technologies and to disseminate this data to D&D professionals in a manner that will facilitate the review and selection of technologies to perform decontamination and decommissioning. The objectives for this project include the following: Determine technology needs through review of the Site Technology Coordination Group (STCG) information and other applicable websites and needs databases; Perform a detailed review of industries that perform similar activities as those required in D&D operations to identify additional technologies; Define the technology assessment program for characterization and waste management problem sets; Define the data management program for characterization, dismantlement, and waste management problem sets; Evaluate baseline and innovative technologies under standard test conditions at Florida International University's Hemispheric Center for Environmental Technology (FIU-HCET) and other locations and collect data in the areas of performance, cost, health and safety, operations and maintenance, and primary and secondary waste generation; Continue to locate, verify, and incorporate technology performance data from other sources into the multimedia information system; and Develop the conceptual design for a dismantlement technology decision analysis tool for dismantlement technologies.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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 ...

  2. 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.

  3. Phase lags of solar hemispheric cycles

    CERN Document Server

    Muraközy, J

    2013-01-01

    The North-South asymmetry of solar activity is variable in time and strength. We analyse the long-term variation of the phase lags of hemispheric cycles and check a conjectured relationship between these phase lags and the hemispheric cycle strengths. Sunspot data are used from cycles 12-23 in which the separation of northern and southern hemispheres is possible. The centers of mass of the hemispheric cycle profiles were used to study the phase relations and relative strengths of the hemispheric cycles. This approach considers a cycle as a whole and disregards the short-term fluctuations of the cycle time profile. The phase of the hemispheric cycles shows an alternating variation: the northern cycle leads in 4 cycles and follows in 4 cycles. No significant relationship is found between the phase and strength differences of the hemispheric cycles. The period of 4+4 cycles appears to be close to the Gleissberg cycle and may provide a key to its physical background. It may raise a new aspect in the solar dynamo ...

  4. 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.

  5. 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.

  6. 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.

  7. 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...

  8. Remote canopy hemispherical image collection system

    Science.gov (United States)

    Wan, Xuefen; Liu, Bingyu; Yang, Yi; Han, Fang; Cui, Jian

    2016-11-01

    Canopies are major part of plant photosynthesis and have distinct architectural elements such as tree crowns, whorls, branches, shoots, etc. By measuring canopy structural parameters, the solar radiation interception, photosynthesis effects and the spatio-temporal distribution of solar radiation under the canopy can be evaluated. Among canopy structure parameters, Leaf Area Index (LAI) is the key one. Leaf area index is a crucial variable in agronomic and environmental studies, because of its importance for estimating the amount of radiation intercepted by the canopy and the crop water requirements. The LAI can be achieved by hemispheric images which are obtained below the canopy with high accuracy and effectiveness. But existing hemispheric images canopy-LAI measurement technique is based on digital SLR camera with a fisheye lens. Users need to collect hemispheric image manually. The SLR camera with fisheye lens is not suit for long-term canopy-LAI outdoor measurement too. And the high cost of SLR limits its capacity. In recent years, with the development of embedded system and image processing technology, low cost remote canopy hemispheric image acquisition technology is becoming possible. In this paper, we present a remote hemispheric canopy image acquisition system with in-field/host configuration. In-field node based on imbed platform, low cost image sensor and fisheye lens is designed to achieve hemispherical image of plant canopy at distance with low cost. Solar radiation and temperature/humidity data, which are important for evaluating image data validation, are obtained for invalid hemispherical image elimination and node maintenance too. Host computer interacts with in-field node by 3G network. The hemispherical image calibration and super resolution are used to improve image quality in host computer. Results show that the remote canopy image collection system can make low cost remote canopy image acquisition for LAI effectively. It will be a potential

  9. 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...

  10. 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.

  11. 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.)

  12. Microbial community structures and in situ sulfate-reducing and sulfur-oxidizing activities in biofilms developed on mortar specimens in a corroded sewer system.

    Science.gov (United States)

    Satoh, Hisashi; Odagiri, Mitsunori; Ito, Tsukasa; Okabe, Satoshi

    2009-10-01

    Microbially induced concrete corrosion (MICC) caused by sulfuric acid attack in sewer systems has been a serious problem for a long time. A better understanding of microbial community structures of sulfate-reducing bacteria (SRB) and sulfur-oxidizing bacteria (SOB) and their in situ activities is essential for the efficient control of MICC. In this study, the microbial community structures and the in situ hydrogen sulfide production and consumption rates within biofilms and corroded materials developed on mortar specimens placed in a corroded manhole was investigated by culture-independent 16S rRNA gene-based molecular techniques and microsensors for hydrogen sulfide, oxygen, pH and the oxidation-reduction potential. The dark-gray gel-like biofilm was developed in the bottom (from the bottom to 4 cm) and the middle (4-20 cm from the bottom of the manhole) parts of the mortar specimens. White filamentous biofilms covered the gel-like biofilm in the middle part. The mortar specimens placed in the upper part (30 cm above the bottom of the manhole) were corroded. The 16S rRNA gene-cloning analysis revealed that one clone retrieved from the bottom biofilm sample was related to an SRB, 12 clones and 6 clones retrieved from the middle biofilm and the corroded material samples, respectively, were related to SOB. In situ hybridization results showed that the SRB were detected throughout the bottom biofilm and filamentous SOB cells were mainly detected in the upper oxic layer of the middle biofilm. Microsensor measurements demonstrated that hydrogen sulfide was produced in and diffused out of the bottom biofilms. In contrast, in the middle biofilm the hydrogen sulfide produced in the deeper parts of the biofilm was oxidized in the upper filamentous biofilm. pH was around 3 in the corroded materials developed in the upper part of the mortar specimens. Therefore, it can be concluded that hydrogen sulfide provided from the bottom biofilms and the sludge settling tank was

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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...

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  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. 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 ...

  5. 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.

  6. 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.

  7. Differential hemispheric modulation of preparatory attention.

    Science.gov (United States)

    Fernández, Laura Gabriela; Siéroff, Eric

    2014-06-01

    Preparatory attention (PA) is the ability to allocate attention to a stimulus prior to its occurrence and is a crucial component of attentional control. We investigated the role of brain hemispheres in PA using an experimental test in which normal participants responded to a target that could appear in the right or the left visual fields, thus projecting to the left or the right hemispheres, while ignoring a central distractor that could appear in the preparatory phase preceding the target. This experimental test measures the ability of participants to modulate PA directed to a target location when the probability of a distractor occurrence varies across three blocks of trials (0%, 33%, 67%). The competition between distractors and target for PA should produce slower response times when the probability of distractors is high. Three experiments were conducted varying the temporal predictability of the target occurrence within a trial (high predictability in Experiments 1 and 3, and low predictability in Experiment 2), and the task used (location in Experiments 1 and 2, and detection in Experiment 3). We found that the modulation of PA by the expected probability of events was different in each visual field/hemisphere. Whereas the left hemisphere PA was influenced by the mere probability of events in each block of trials, the right hemisphere PA was mainly influenced by events with high temporal predictability. These results suggest that each hemisphere uses a different strategy to modulate PA when directed to a target location at the perceptual level of visual processing.

  8. 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.

  9. Northern Hemisphere forcing of Southern Hemisphere climate during the last deglaciation.

    Science.gov (United States)

    He, Feng; Shakun, Jeremy D; Clark, Peter U; Carlson, Anders E; Liu, Zhengyu; Otto-Bliesner, Bette L; Kutzbach, John E

    2013-02-07

    According to the Milankovitch theory, changes in summer insolation in the high-latitude Northern Hemisphere caused glacial cycles through their impact on ice-sheet mass balance. Statistical analyses of long climate records supported this theory, but they also posed a substantial challenge by showing that changes in Southern Hemisphere climate were in phase with or led those in the north. Although an orbitally forced Northern Hemisphere signal may have been transmitted to the Southern Hemisphere, insolation forcing can also directly influence local Southern Hemisphere climate, potentially intensified by sea-ice feedback, suggesting that the hemispheres may have responded independently to different aspects of orbital forcing. Signal processing of climate records cannot distinguish between these conditions, however, because the proposed insolation forcings share essentially identical variability. Here we use transient simulations with a coupled atmosphere-ocean general circulation model to identify the impacts of forcing from changes in orbits, atmospheric CO(2) concentration, ice sheets and the Atlantic meridional overturning circulation (AMOC) on hemispheric temperatures during the first half of the last deglaciation (22-14.3 kyr BP). Although based on a single model, our transient simulation with only orbital changes supports the Milankovitch theory in showing that the last deglaciation was initiated by rising insolation during spring and summer in the mid-latitude to high-latitude Northern Hemisphere and by terrestrial snow-albedo feedback. The simulation with all forcings best reproduces the timing and magnitude of surface temperature evolution in the Southern Hemisphere in deglacial proxy records. AMOC changes associated with an orbitally induced retreat of Northern Hemisphere ice sheets is the most plausible explanation for the early Southern Hemisphere deglacial warming and its lead over Northern Hemisphere temperature; the ensuing rise in atmospheric CO(2

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. Combined electron microscopy and vibrational spectroscopy study of corroded Magnox sludge from a legacy spent nuclear fuel storage pond

    Science.gov (United States)

    Gregson, Colin R.; Goddard, David T.; Sarsfield, Mark J.; Taylor, Robin J.

    2011-05-01

    Samples of filtered particulates and sludges, formed from corroding magnesium alloy clad uranium metal ("Magnox") fuel elements, collected from one of the legacy nuclear fuel storage ponds located at Sellafield (UK) were investigated by Environmental Scanning Electron Microscopy with Energy Dispersive X-Ray analysis (ESEM/EDX), micro-Raman spectroscopy and Fourier transform infra-red spectroscopy (FT-IR). ESEM imaging confirmed the dominant morphology to be clusters of interlocking platelets typical of brucite (Mg(OH) 2). EDX analysis was suggestive of some conversion to the related phase, hydrotalcite (Mg 6Al 2(CO 3)(OH) 16·4H 2O), due to elevated levels of Al associated with Mg. Other apparent morphologies were less commonly observed including flaky sheets, consistent with earlier stages of Magnox alloy corrosion. In a few specific cases, rods were also observed suggestive of some conversion to Mg-hydroxycarbonate phases. Discrete phases rich in U were also identified. Fluorescence in the Raman spectroscopy also indicated surface coatings of organic macromolecules and iron sulphide on hematite containing particles, attributed to microbial activity within the open air pond. Some specific differences in the solid phases between pond areas with differing conditions were apparent.

  17. 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.

  18. Anti-corrosion Painting of Corroded Transmission Towers%锈蚀输电铁塔涂装体系耐蚀性

    Institute of Scientific and Technical Information of China (English)

    陈颖敏; 俞立; 侯玉婧

    2012-01-01

    The performance of phosphating solution used as pretreatment agent of corroded transmission towers was studied and the matchable coating system was developed.The results of treatment of corroded transmission towers by phosphating solution showed that in forming the process of a dense protection film of phosphate on the surface of corroded steel,the phosphating liquid cleaning,rust conversion,zinc phosphating and surface conditioning were finished at the same time.The results also showed that using organic coatings as primer,the coating system had a good performance in mechanical properties and corrosion resistance with the matchable phosphating solution.%采用磷化技术处理锈蚀输电铁塔,并在此基础上设计出与磷化液配套的防腐蚀涂装体系。试验结果表明,使用磷化技术处理锈蚀铁塔时,磷化液在锈蚀金属表面形成致密磷酸盐膜,清洗、锈层转化、锌层磷化以及表面调整可以一步完成;配制的涂装体系中,以有机涂料为底漆的涂装体系与磷化液配套使用机械性能与耐蚀性能良好。

  19. 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.

  20. Music Appreciation and Hemisphere Orientation: Visual versus Verbal Involvement.

    Science.gov (United States)

    Zalanowski, Annette H.

    1990-01-01

    Analyzes effect of brain hemisphere orientation on music appreciation. Reports results from 36 left-hemisphere and 36 right-hemisphere undergraduates who responded to a musical selection verbally or visually. Finds right-hemisphere students show greater appreciation, measured by attention, understanding, and enjoyment scores. Discusses…

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Hemispheric dysplasia and hemimegalencephaly: imaging definitions.

    Science.gov (United States)

    Santos, Antonio Carlos; Escorsi-Rosset, Sara; Simao, Gustavo N; Terra, Vera C; Velasco, Tonicarlo; Neder, Luciano; Sakamoto, Americo C; Machado, Helio R

    2014-11-01

    Hemispheric dysplasia (HD) and hemimegalencephaly (HME) are both brain malformations with early clinical manifestation including developmental delay and intractable epilepsy. Sometimes the differentiation of these conditions is not simple. HME is an anomaly of cortical development caused by a combination of neural proliferation and cell migration dysfunction, showing lobar or hemispheric enlargement. On the other hand, HD shows no brain hypertrophy, and even brain atrophy, eventually. To compare both conditions, we reviewed clinical, MRI, and histopathology of 23 patients with developmental delay and refractory epilepsy treated with hemispheric surgery. Histologically, both groups presented polymicrogyria, focal cortical dysplasia, gray matter (GM) heterotopia, pachygyria, and agyria. The white matter (WM) showed different degrees of gliosis and myelin impairment. Even though with no specificity in histopathology, the degree of lesion was more impressive on HME. The combination of WM dysmyelination and hypertrophy leads to the so called hamartomatous appearing. Although not all HME showed brain enlargement and some HD might show no size changes or atrophy, the size of affected hemisphere and the hamartomatous appearance of the WM were the more relevant signs to differentiate both conditions. Brain MRI was the best diagnostic tolls because it allowed together high contrast resolution, whole brain coverage and spatial distribution analysis. HD and HMD showed brain asymmetry tendency, but in opposite directions. The size of affected hemisphere and the hamartomatous appearance of the WM were the more relevant signs to differentiate both conditions.

  6. 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.

  7. 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.

  8. 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.

  9. Hyperlalia: A Right Cerebral Hemisphere Syndrome

    Directory of Open Access Journals (Sweden)

    Atsushi Yamadori

    1990-01-01

    Full Text Available We describe a new right hemispheric behavioural syndrome for which we propose the name “hyperlalia”. In a typical case an apparently unconcerned and expressionless patient is easily prompted to remarkable volubility with a content which is loose and incoherent. The voice is low and monotonous. All the lesions confirmed by computed tomography of the brain overlapped in the perisylvian area in the territory of the right middle cerebral artery. Loss of a subtle balance between the left hemispheric speech area and the corresponding area in the right hemisphere caused by acute damage of the right perisylvian area may have resulted in disinhibition of the speech function. Similarities and dissimilarities with the known pathology of talkativeness are also discussed.

  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. Clostridium kogasensis sp. nov., a novel member of the genus Clostridium, isolated from soil under a corroded gas pipeline.

    Science.gov (United States)

    Shin, Yeseul; Kang, Seok-Seong; Paek, Jayoung; Jin, Tae Eun; Song, Hong Seok; Kim, Hongik; Park, Hee-Moon; Chang, Young-Hyo

    2016-06-01

    Two bacterial strains, YHK0403(T) and YHK0508, isolated from soil under a corroded gas pipe line, were revealed as Gram-negative, obligately anaerobic, spore-forming and mesophilic bacteria. The cells were rod-shaped and motile by means of peritrichous flagella. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the isolates were members of the genus Clostridium and were the most closely related to Clostridium scatologenes KCTC 5588(T) (95.8% sequence similarity), followed by Clostridium magnum KCTC 15177(T) (95.8%), Clostridium drakei KCTC 5440(T) (95.7%) and Clostridium tyrobutyricum KCTC 5387(T) (94.9%). The G + C contents of the isolates were 29.6 mol%. Peptidoglycan in the cell wall was of the A1γ type with meso-diaminopimelic acid. The major polar lipid was diphosphatidylglycerol (DPG), and other minor lipids were revealed as phosphatidylglycerol (PG), phosphatidylethanolamine (PE), two unknown glycolipids (GL1 and GL2), an unknown aminoglycolipid (NGL), two unknown aminophospholipids (PN1 and PN2) and four unknown phospholipids (PL1 to PL4). Predominant fatty acids were C16:0 and C16:1cis9 DMA. The major end products from glucose fermentation were identified as butyrate (12.2 mmol) and acetate (9.8 mmol). Collectively, the results from a wide range of phenotypic tests, chemotaxonomic tests, and phylogenetic analysis indicated that the two isolates represent novel species of the genus Clostridium, for which the name Clostridium kogasensis sp. nov. (type strain, YHK0403(T) = KCTC 15258(T) = JCM 18719(T)) is proposed.

  20. Isolation of a Sulfur-oxidizing Bacterium That can Grow under Alkaline pH, from Corroded Concrete.

    Science.gov (United States)

    Maeda, T; Negishi, A; Oshima, Y; Nogami, Y; Kamimura, K; Sugio, T

    1998-01-01

    To study the early stages of concrete corrosion by bacteria, sulfur-oxidizing bacterium strain RO-1, which grows in an alkaline thiosulfate medium (pH 10.0) was isolated from corroded concreate and characterized. Strain RO-1 was a Gram negative, rod-shaped bacterium (0.5-0.6×0.9-1.5 μm). The mean G+C content of the DNA of strain RO-1 was 65.0 mol%. Optimum pH and temperature for growth were 8.0. and 30-37°C, respectively. When grown in thiosulfate medium with pH 10.0, growth rate of the strain was 48% of that observed at the optimum pH for growth. Strain RO-1 used sulfide, thiosulfate, and glucose, but not elemental sulfur or tetrathionate, as a sole energy source. Strain RO-1 grew under anaerobic conditions in pepton-NO3 (-) medium containing sodium nitrate as an electron acceptor, and had enzyme activities that oxidized sulfide, elemental sulfur, thiosulfate, sulfite, and glucose, but not tetrathionate. The bacterium had an activity to assimilate (14)CO2 into the cells when thiosulfate was used as an energy source. These results suggest that strain RO-1 is Thiobacillus versutus. Strain RO-1 exuded Ca(2+) from concrete blocks added to thiosulfate medium with pH 9.0 and the pH of the medium decreased from 9.0 to 5.5 after 22 days of cultivation. In contrast, Thiobacillus thiooxidans strain NB1-3 could not exude Ca(2+) in the same thiosulfate medium, suggesting that strain RO-1, but not T. thiooxidans NB1-3, is involved in the early stage of concrete corrosion because concrete structures just after construction contain calcium hydroxide and have a pH of 12-13.

  1. Survey results of corroding problems at biological treatment plants, Stage II Protection of concrete - State of the Art

    Energy Technology Data Exchange (ETDEWEB)

    Edwards, Ylva (CBI, Boraas (Sweden)); Henriksson, Gunilla (SP, Boraas (Sweden))

    2011-07-01

    A pilot study on the degradation and corrosion of concrete in biological treatment plants was conducted in 2009/2010 in a Waste Refinery Project WR-27 'Survey results of corroding problems at biological treatment plants'. The results showed that the concrete does not have sufficient resistance in the current aggressive plant environment. Furthermore, it is stated that some form of surface protection system is needed to ensure the good performance of concrete constructions, and that the system must withstand the aggressive environment and the traffic that occurs on site. Consequently, a new study was proposed in order to develop specifications for surface protection of concrete in aggressive food waste environments. Results from that study are presented in this report. The report includes various types of waterproofing/protection coating for concrete in biological treatment plants. A number of proposals from the industry are presented in the light of results from project WR-27, i.e., the materials must, among other things, withstand the aggressive leachate from waste food at temperatures up to 70 deg C, and some degree of wear. Some systems are compared in terms of technical material properties as reported by the manufacturer. It turns out that different testing methods were used, and the test results are thus generally not directly comparable. A proposal for a test program has been developed, focusing on chemical resistance and wear resistance. A test solution corresponding to leachate is specified. Laboratory tests for verification of the proposed methodology and future requirements are proposed, as well as test sites and follow-up in the field

  2. Right hemisphere grey matter structure and language outcomes in chronic left hemisphere stroke.

    Science.gov (United States)

    Xing, Shihui; Lacey, Elizabeth H; Skipper-Kallal, Laura M; Jiang, Xiong; Harris-Love, Michelle L; Zeng, Jinsheng; Turkeltaub, Peter E

    2016-01-01

    The neural mechanisms underlying recovery of language after left hemisphere stroke remain elusive. Although older evidence suggested that right hemisphere language homologues compensate for damage in left hemisphere language areas, the current prevailing theory suggests that right hemisphere engagement is ineffective or even maladaptive. Using a novel combination of support vector regression-based lesion-symptom mapping and voxel-based morphometry, we aimed to determine whether local grey matter volume in the right hemisphere independently contributes to aphasia outcomes after chronic left hemisphere stroke. Thirty-two left hemisphere stroke survivors with aphasia underwent language assessment with the Western Aphasia Battery-Revised and tests of other cognitive domains. High-resolution T1-weighted images were obtained in aphasia patients and 30 demographically matched healthy controls. Support vector regression-based multivariate lesion-symptom mapping was used to identify critical language areas in the left hemisphere and then to quantify each stroke survivor's lesion burden in these areas. After controlling for these direct effects of the stroke on language, voxel-based morphometry was then used to determine whether local grey matter volumes in the right hemisphere explained additional variance in language outcomes. In brain areas in which grey matter volumes related to language outcomes, we then compared grey matter volumes in patients and healthy controls to assess post-stroke plasticity. Lesion-symptom mapping showed that specific left hemisphere regions related to different language abilities. After controlling for lesion burden in these areas, lesion size, and demographic factors, grey matter volumes in parts of the right temporoparietal cortex positively related to spontaneous speech, naming, and repetition scores. Examining whether domain general cognitive functions might explain these relationships, partial correlations demonstrated that grey matter

  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. 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.

  12. 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...

  13. 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...

  14. 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.

  15. 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.

  16. 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....

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. An Evaluative Review of Hemispheric Learning Potential

    Science.gov (United States)

    1985-10-01

    function in the cerebral cortex first assumed importance in the work of the phrenologist Franz Joseph Gall. The early 19th-century neu- rologists...Einstein, Picasso, Kafka , and Eileen Garrett. Cortes and Montezuma are also opposed as the contrast of two hemisphere styles. Moore (1984) integrated

  3. Forest carbon sinks in the northern hemisphere

    NARCIS (Netherlands)

    Goodale, C.L.; Apps, M.J.; Birdsey, R.A.; Field, C.B.; Heath, L.S.; Houghton, R.A.; Jenkins, J.C.; Kohlmaier, G.H.; Kurz, W.; Liu, S.R.; Nabuurs, G.J.; Nilsson, S.; Shvidenko, A.Z.

    2002-01-01

    There is general agreement that terrestrial systems in the Northern Hemisphere provide a significant sink for atmospheric CO2; however, estimates of the magnitude and distribution of this sink vary greatly. National forest inventories provide strong, measuretment-based constraints on the magnitude o

  4. Hemisphere jet mass distribution at finite Nc

    Directory of Open Access Journals (Sweden)

    Yoshikazu Hagiwara

    2016-05-01

    Full Text Available We perform the leading logarithmic resummation of nonglobal logarithms for the single-hemisphere jet mass distribution in e+e− annihilation including the finite-Nc corrections. The result is compared with the previous all-order result in the large-Nc limit as well as fixed-order perturbative calculations.

  5. Hemispheric Differences in Processing Handwritten Cursive

    Science.gov (United States)

    Hellige, Joseph B.; Adamson, Maheen M.

    2007-01-01

    Hemispheric asymmetry was examined for native English speakers identifying consonant-vowel-consonant (CVC) non-words presented in standard printed form, in standard handwritten cursive form or in handwritten cursive with the letters separated by small gaps. For all three conditions, fewer errors occurred when stimuli were presented to the right…

  6. Hemispheric Coupling: Comparing Dynamo Simulations and Observations

    CERN Document Server

    Norton, Aimee A; Passos, Dario

    2014-01-01

    Numerical simulations that reproduce solar-like magnetic cycles can be used to generate long-term statistics. The variations in N-S hemispheric cycle synchronicity and amplitude produced in simulations has not been widely compared to observations. The observed limits on asymmetry show that hemispheric sunspot area production is no more than 20% asymmetric for cycles 12-23 and phase lags do not exceed 20% (2 yrs) of the total cycle period. Independent studies have found a long-term trend in phase values as one hemisphere leads the other for ~four cycles. Such persistence in phase is not indicative of a stochastic phenomenon. We compare the findings to results from a numerical simulation of solar convection recently produced with the EULAG-MHD model. This simulation spans 1600 yrs and generated 40 regular, sunspot-like cycles. While the simulated cycle length is too long and the toroidal bands remain at too high of latitudes, some solar-like aspects of hemispheric asymmetry are reproduced. The model reproduces ...

  7. Morphology of Southern Hemisphere Riometer Auroral Absorption

    Science.gov (United States)

    2006-06-01

    range of frequencies used an inverse -square frequency dependence approximately holds. Morphology of Southern Hemisphere Riometer Auroral Absorption...Tecnológico under Proyecto No 1940934. Annex The percentage probability, QA, that an absorption A dB is exceed, is given as: Where Am is

  8. Forest carbon sinks in the Northern Hemisphere

    Science.gov (United States)

    Christine L. Goodale; Michael J. Apps; Richard A. Birdsey; Christopher B. Field; Linda S. Heath; Richard A. Houghton; Jennifer C. Jenkins; Gundolf H. Kohlmaier; Werner Kurz; Shirong Liu; Gert-Jan Nabuurs; Sten Nilsson; Anatoly Z. Shvidenko

    2002-01-01

    There is general agreement that terrestrial systems in the Northern Hemisphere provide a significant sink for atmospheric CO2; however, estimates of the magnitude and distribution of this sink vary greatly. National forest inventories provide strong, measurement-based constraints on the magnitude of net forest carbon uptake. We brought together...

  9. Hemisphere Susceptibility and Personality: a Replication Study

    Science.gov (United States)

    Dimond, Stuart; Beaumont, Graham

    1974-01-01

    Author studied the capacity of the normal brain to carry out a paired-associate learning task by projecting the stimulus material to either the right or left hemisphere in order to establish if there was a lateral specialization for this type of learning in the normal brain. (Author/RK)

  10. Rethinking a Right Hemisphere Deficit in ADHD

    Science.gov (United States)

    Hale, T. Sigi; Loo, Sandra K.; Zaidel, Eran; Hanada, Grant; Macion, James; Smalley, Susan L.

    2009-01-01

    Introduction: Early observations from lesion studies suggested right hemisphere (RH) dysfunction in ADHD. However, a strictly right-lateralized deficit has not been well supported. An alternatively view suggests increased R greater than L asymmetry of brain function and abnormal interhemispheric interaction. If true, RH pathology in ADHD should…

  11. HEMISPHERE PREFERENCE, ANXIETY, AND COVARIATION BIAS

    NARCIS (Netherlands)

    de Jong, Peter; MERCKELBACH, H; NIJMAN, H

    1995-01-01

    In Study I, normal subjects (N = 70) completed the Preference Test (PT), the Spielberger State-Trait Anxiety Inventory, and the Anxiety Sensitivity Index. Subjects with a preference for a right hemisphere thinking style (as indexed by PT) were found to have higher state anxiety and anxiety sensitivi

  12. Practice makes two hemispheres almost perfect.

    Science.gov (United States)

    Cherbuin, Nicolas; Brinkman, Cobie

    2005-08-01

    Some tasks produce a performance advantage for conditions that require the processing of stimuli in two visual fields compared to conditions where single hemifield processing is sufficient. This advantage, however, disappears with practice. Although no definitive evidence yet exists, there are several possible mechanisms that might lead to improved performance of within- compared to across-hemisphere processing with practice. These include a shift from a more demanding, algorithmic strategy to a less demanding memory-retrieval strategy (e.g., [G. Logan, Toward an instance theory of automatisation. Psych. Rev. 95 (1988) 492-527]), as discussed by Weissman and Compton [D.H. Weissman, R.J. Compton, Practice makes a hemisphere perfect: the advantage of interhemispheric recruitment is eliminated with practice. Laterality, 8 (4) (2003) 361-375], and/or a more generalised practice effect [K. Kirsner, C. Speelman, Skill acquisition and repetition priming: one principle, many processes? J. Exp. Psychol., Learn. Mem. Cogn., 22 (1996) 563-575]. Contrary to Weissman and Compton findings, our results suggest that although single-hemisphere performance improves with practice, bi-hemispheric performance also improves substantially. Furthermore, these effects do not appear to be due to a shift in strategy but rather due to a general practice effect.

  13. 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

  14. 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.

  15. 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.

  16. 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...

  17. 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 ...

  18. 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 ...

  19. 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 ...

  20. 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 ...

  1. 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 ...

  2. 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 ...

  3. 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 ...

  4. 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.

  5. 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.

  6. 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.

  7. 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...

  8. 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...

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Resting state EEG power, intra-hemisphere and inter-hemisphere coherence in bipolar disorder

    Science.gov (United States)

    Handayani, Nita; Khotimah, S. N.; Haryanto, F.; Arif, I.; Taruno, Warsito P.

    2017-02-01

    This paper examines the differences of EEG power and coherence between bipolar disorder patients and healthy subjects in the resting state. Observations are focused on the prefrontal cortex area by calculating intra-hemisphere and inter-hemisphere coherence. EEG data acquisition are conducted by using wireless Emotiv Epoc on AF3, AF4, FC5, FC6, F7 and F8 channels. The power spectral analysis shows that in bipolar disoder there is an increase of power in the delta, theta and beta frequencies, and power decrease in the alpha frequency. The coherence test results show that both intra-hemisphere and inter-hemisphere coherence in bipolar disorder patients are lower than healthy subjects. This shows the lack of brain synchronization in bipolar disorder patients.

  14. 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.

  15. 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.

  16. Onsite-effects of dual-hemisphere versus conventional single-hemisphere transcranial direct current stimulation

    OpenAIRE

    Kwon, Yong Hyun; Jang, Sung Ho

    2012-01-01

    We performed functional MRI examinations in six right-handed healthy subjects. During functional MRI scanning, transcranial direct current stimulation was delivered with the anode over the right primary sensorimotor cortex and the cathode over the left primary sensorimotor cortex using dual-hemispheric transcranial direct current stimulation. This was compared to a cathode over the left supraorbital area using conventional single-hemispheric transcranial direct current stimulation. Voxel coun...

  17. The long term effects of cathodic protection on corroding, pre-stressed concrete structures: Hydrogen embrittlement of the reinforcing steel

    Science.gov (United States)

    Enos, David George

    Assessment of the effect of cathodic protection on a chloride contaminated bridge pile involves the definition of the hydrogen embrittlement behavior of the pearlitic reinforcement combined with quantification of the local (i.e., at the steel/concrete interface) chemical and electrochemical conditions, both prior to and throughout the application of cathodic protection. The hydrogen embrittlement behavior of the reinforcement was assessed through a combination of Devanathan/Stachurski permeation experiments to quantify subsurface hydrogen concentrations, CsbH, as a function of the applied hydrogen overpotential, eta, and crack initiation tests for bluntly notched and fatigue pre-cracked tensile specimens employing elastic-plastic finite element analysis and linear elastic fracture mechanics, respectively. A threshold mobile lattice hydrogen concentration for embrittlement of 2×10sp{-7} mol/cmsp3 was established for bluntly notched and fatigue pre-cracked specimens. Crack initiation occurred by the formation of shear cracks oriented at an angle approaching 45sp° from the tensile axis, as proposed by Miller and Smith (Miller, 1970), in regions where both the longitudinal and shear stresses were maximized (i.e., near the notch root). These Miller cracks then triggered longitudinal splitting which continued until fast fracture of the remaining ligament occurred. Instrumented laboratory scale piles were constructed and partially immersed in ASTM artificial ocean water. With time, localized corrosion (crevicing) was initiated along the reinforcement, and was accompanied by an acidic shift in the pH of the occluded environment due to ferrous ion hydrolysis. Cathodic protection current densities from -0.1 muA/cmsp2 to -3.0 muA/cmsp2 were applied via a skirt anode located at the waterline. Current densities as low as 0.66 muA/cmsp2 were sufficient to deplete the dissolved oxygen concentration at the steel/concrete interface and result in the observance of hydrogen

  18. Mechanical Analysis of Corroded Reinforced Concrete Beams%锈蚀钢筋混凝土梁受力性能研究

    Institute of Scientific and Technical Information of China (English)

    唐贵和; 黄金林

    2012-01-01

    A discrete finite element model was built using finite element software,which was proved appropriate for the analysis of mechanical behavior of corroded reinforced concrete beams when combined with the degradation model of corroded steel bars and Bteel-eoncrete interface through available research results. Further parametric analysis was carried out to investigate the mechanical behavior of corroded reinforced concrete beams. The results show that; (1) the corrosion rate greatly affects the ultimate bearing capacity, the ultimate bearing capacity, stiffness and ductility will decrease with the increase of corrosion rate, ( 2) the bond stress has little effect on the ultimate bearing capacity, but it greatly affects the failure mode. The beam may be transformed from ductile failure to brittle failure with increasing corrosion rate. These conclusions can be referred to in the rehabilitation design of corroded reinforced concrete beams.%根据已有研究成果建立锈蚀钢筋及钢筋-混凝土界面的性能退化模型,采用有限元软件建立分离式钢筋混凝土梁模型,通过试验验证了数值分析结果的准确性.在此基础上,对锈蚀钢筋混凝土梁的受力性能进行了参数分析.结果表明:(1)钢筋锈蚀率对钢筋混凝土梁受力性能影响较大,随着锈蚀率的增加,构件的承载力降低、刚度退化及延性变差;(2)钢筋-混凝土界面粘结力对钢筋混凝土梁承载力影响较小,但会改变构件的破坏模式,随着锈蚀率增加,构件从延性破坏变为脆性破坏.本文研究成果可为锈蚀钢筋混凝土梁加固设计提供参考.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. Asymmetric auroral intensities in the Earth's Northern and Southern hemispheres

    Science.gov (United States)

    Laundal, K. M.; Østgaard, N.

    2009-07-01

    It is commonly assumed that the aurora borealis (Northern Hemisphere) and aurora australis (Southern Hemisphere) are mirror images of each other because the charged particles causing the aurora follow the magnetic field lines connecting the two hemispheres. The particles are believed to be evenly distributed between the two hemispheres, from the source region in the equatorial plane of the magnetosphere. Although it has been shown that similar auroral features in the opposite hemispheres can be displaced tens of degree in longitude and that seasonal effects can cause differences in global intensity, the overall auroral patterns were still similar. Here we report observations that clearly contradict the common assumption about symmetric aurora: intense spots are seen at dawn in the Northern summer Hemisphere, and at dusk in the Southern winter Hemisphere. The asymmetry is interpreted in terms of inter-hemispheric currents related to seasons, which have been predicted but hitherto had not been seen.

  4. Right-hemispheric processing of non-linguistic word features

    DEFF Research Database (Denmark)

    Baumgaertner, Annette; Hartwigsen, Gesa; Roman Siebner, Hartwig

    2013-01-01

    Verbal stimuli often induce right-hemispheric activation in patients with aphasia after left-hemispheric stroke. This right-hemispheric activation is commonly attributed to functional reorganization within the language system. Yet previous evidence suggests that functional activation in right......-hemispheric homologues of classic left-hemispheric language areas may partly be due to processing nonlinguistic perceptual features of verbal stimuli. We used functional MRI (fMRI) to clarify the role of the right hemisphere in the perception of nonlinguistic word features in healthy individuals. Participants made......, the right inferior frontal gyrus (IFG), an area previously suggested to support language recovery after left-hemispheric stroke, displayed modality-independent activation during perceptual processing of word stimuli. Our findings indicate that activation of the right hemisphere during language tasks may...

  5. Hemispheric differences in the effects of context on vowel perception

    NARCIS (Netherlands)

    Sjerps, M.J.; Mitterer, H.A.; McQueen, J.M.

    2012-01-01

    Listeners perceive speech sounds relative to context. Contextual influences might differ over hemispheres if different types of auditory processing are lateralized. Hemispheric differences in contextual influences on vowel perception were investigated by presenting speech targets and both speech and

  6. 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.

  7. 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.

  8. 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...

  9. 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...

  10. 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

  11. 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.

  12. 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.

  13. 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...

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Spatial disorientation in right-hemisphere infarction.

    OpenAIRE

    Meerwaldt, J D; van Harskamp, F

    1982-01-01

    Spatial orientation was tested with the rod orientation test. The subjects were 40 normal controls and 68 brain-damaged patients with cerebral infarcts. Patients in whom the lesion included the post-rolandic region of the right hemisphere performed worse than controls or patients with lesions at other sites. Patients with an exclusively postrolandic (usually occipital) lesion showed higher error rates than patients with a combined prerolandic and postrolandic lesion, but only for the visual p...

  5. 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.

  6. Cognitive Correlates of Hemispheric Performance on Dichotic Tasks.

    Science.gov (United States)

    Johnson, Ronald C.; And Others

    1984-01-01

    Examined the relationship between performance on left and right hemisphere dominant measures of cognition and performance on dichotic memory tasks in 53 adults age 50 and older. Right hemisphere performance on dichotic and cognitive tasks showed a negative association with age while left hemisphere performance showed no decline. (JAC)

  7. Hemispheric Asymmetries in the Activation and Monitoring of Memory Errors

    Science.gov (United States)

    Giammattei, Jeannette; Arndt, Jason

    2012-01-01

    Previous research on the lateralization of memory errors suggests that the right hemisphere's tendency to produce more memory errors than the left hemisphere reflects hemispheric differences in semantic activation. However, all prior research that has examined the lateralization of memory errors has used self-paced recognition judgments. Because…

  8. Double infarction in one cerebral hemisphere.

    Science.gov (United States)

    Bogousslavsky, J

    1991-07-01

    Thirty-two patients whose first stroke was due to double infarct in one cerebral hemisphere were identified among 1,911 consecutive patients from the Lausanne Stroke Registry. The double infarct involved territories of the superficial middle cerebral artery, superficial posterior cerebral artery, lenticulostriate, anterior choroidal artery, or borderzone. The most common combination involved territories of the anterior middle cerebral artery plus the posterior middle cerebral artery. In the patients with the double infarct, the prevalence of potential cardiac sources of embolism (19%) was similar to that found in the registry in general, but the double infarct was closely associated with tight (greater than or equal to 90% of the lumen diameter) stenosis or occlusion (75%) of the internal carotid artery. The most common neurological picture mimicked large infarction in the middle cerebral artery territory, but nearly half of the patients with double infarct in one cerebral hemisphere had a specific clinical syndrome, which was not found in the 1,879 remaining patients from the registry, including hemianopia-hemiplegia (in 6), acute conduction aphasia-hemiparesis (in 2), and acute transcortical mixed aphasia (in 6), in relation to characteristic combinations of infarcts. These unique clinical and etiological correlates warrant the recognition of double infarct in one cerebral hemisphere from other acute ischemic strokes.

  9. Depression and the hyperactive right-hemisphere.

    Science.gov (United States)

    Hecht, David

    2010-10-01

    Depression is associated with an inter-hemispheric imbalance; a hyperactive right-hemisphere (RH) and a relatively hypoactive left-hemisphere (LH). Nevertheless, the underlying mechanisms which can explain why depression is associated with a RH dominance remain elusive. This article points out the potential links between functional cerebral asymmetries and specific symptoms and features of depression. There is evidence that the RH is selectively involved in processing negative emotions, pessimistic thoughts and unconstructive thinking styles--all which comprise the cognitive phenomenology of depression and in turn contribute to the elevated anxiety, stress and pain associated with the illness. Additionally, the RH mediates vigilance and arousal which may explain the sleep disturbances often reported in depression. The RH had also been linked with self-reflection, accounting for the tendency of depressed individuals to withdraw from their external environments and focus attention inward. Physiologically, RH activation is associated with hyprecortisolemia, which contributes to the deterioration of the immune system functioning and puts depressed patients at a greater risk of developing other illnesses, accounting for depression's high comorbidity with other diseases. Conversely, the LH is specifically involved in processing pleasurable experiences, and its relative attenuation is in line with the symptoms of anhedonia that characterize depression. The LH is also relatively more involved in decision-making processes, accounting for the indecisiveness that is often accompanied with depression.

  10. Antireflective characteristics of hemispherical grid grating

    Institute of Scientific and Technical Information of China (English)

    REN Zhibin; JIANG Huilin; LIU Guojun; SUN Qiang

    2005-01-01

    In this paper, the optical characteristics of new type hemispherical grid subwavelength grating are studied by using multi-level column structure approximation and rigorous coupled-wave analysis. This kind of grating could be fabricated by chemical methods, thus simplifying the fabrication technology of subwavelength gratings for visible light. By computer simulation and calculation, the hemispherical grid subwavelength gratings are proved to have antireflective characteristics. Two design schemes of this kind of grating are presented. In the first scheme, the grating could achieve a reflectivity as low as 3.4416×10-7, which can be adapted to 0.46―0.7 μm of visible waveband and ±12° incident angle field. In the second scheme, the grating can achieve a reflectivity as low as 3.112×10-4 and adapted to the whole visible waveband and ±23° incident angle field. The application field of the latter scheme is wider than that of the former. The results of this paper could provide reference for the applications of the hemispherical grid subwavelength gratings for the visible waveband.

  11. Casimir effect in hemisphere capped tubes

    CERN Document Server

    de Mello, E R Bezerra

    2014-01-01

    In this paper we investigate the vacuum densities for a massive scalar field with general curvature coupling in background of a (2+1)-dimensional spacetime corresponding to a cylindrical tube with a hemispherical cap. A complete set of mode functions is constructed and the positive-frequency Wightman function is evaluated for both the cylindrical and hemispherical subspaces. On the base of this, the vacuum expectation values of the field squared and energy-momentum tensor are investigated. The mean field squared and the normal stress are finite on the boundary separating two subspaces, whereas the energy density and the parallel stress diverge as the inverse power of the distance from the boundary. For a conformally coupled field, the vacuum energy density is negative on the cylindrical part of the space. On the hemisphere, it is negative near the top and positive close to the boundary. In the case of minimal coupling the energy density on the cup is negative. On the tube it is positive near the boundary and ...

  12. Casimir Effect in Hemisphere Capped Tubes

    Science.gov (United States)

    Bezerra de Mello, E. R.; Saharian, A. A.

    2016-02-01

    In this paper we investigate the vacuum densities for a massive scalar field with general curvature coupling in background of a (2 + 1)-dimensional spacetime corresponding to a cylindrical tube with a hemispherical cap. A complete set of mode functions is constructed and the positive-frequency Wightman function is evaluated for both the cylindrical and hemispherical subspaces. On the base of this, the vacuum expectation values of the field squared and energy-momentum tensor are investigated. The mean field squared and the normal stress are finite on the boundary separating two subspaces, whereas the energy density and the parallel stress diverge as the inverse power of the distance from the boundary. For a conformally coupled field, the vacuum energy density is negative on the cylindrical part of the space. On the hemisphere, it is negative near the top and positive close to the boundary. In the case of minimal coupling the energy density on the cup is negative. On the tube it is positive near the boundary and negative at large distances. Though the geometries of the subspaces are different, the Casimir pressures on the separate sides of the boundary are equal and the net Casimir force vanishes. The results obtained may be applied to capped carbon nanotubes described by an effective field theory in the long-wavelength approximation.

  13. 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.

  14. 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.

  15. 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.

  16. 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...

  17. Testing the Language of German Cerebral Palsy Patients with Right Hemispheric Language Organization after Early Left Hemispheric Damage

    Science.gov (United States)

    Schwilling, Eleonore; Krageloh-Mann, Ingeborg; Konietzko, Andreas; Winkler, Susanne; Lidzba, Karen

    2012-01-01

    Language functions are generally represented in the left cerebral hemisphere. After early (prenatally acquired or perinatally acquired) left hemispheric brain damage language functions may be salvaged by reorganization into the right hemisphere. This is different from brain lesions acquired in adulthood which normally lead to aphasia. Right…

  18. 锈蚀钢框架地震损伤模型研究%Seismic damage model of a corroded steel frame

    Institute of Scientific and Technical Information of China (English)

    郑山锁; 王晓飞; 程洋; 孙乐彬

    2015-01-01

    In order to reasonably describe the seismic damage forms of a corroded steel frame and the effects of different levels of corrosion on the aseismic performance of steel frames,on the basis of the seismic damage model of steel structures proposed by Ou Jinping,et al,the seismic damage model of a corroded steel frame was built.To determine the seismic damage model parameters of a corroded steel structure,the calculation methods of the bilinear restoring force model feature points of corroded beams and columns member were presented,and other parameter values were obtained with elastic-plastic time history analysis.Using the weighted partial coefficients method,the multi-scale effect of migration and conversion from member damage to structure damage was considered,the overall seismic damage model of a corroded steel frame was established.Combined with the characteristics of the damage model proposed here,the corresponding structural damage index ranges with different damage levels were defined.Finally,the elastic-plastic time history analyses were performed for 5 specimens of flat steel frame structures with different corrosion rates,the results showed that the damage model proposed here can reflect the degradation law of steel frame structures with variation of corrosion level in a certain extent.%为了合理地描述锈蚀钢框架的地震破坏形式及不同程度的锈蚀对钢框架抗震性能的影响,在欧进萍等人提出的钢结构地震损伤模型的基础上建立锈蚀钢结构地震损伤模型。为确定锈蚀钢结构地震损伤模型参数,分别给出锈蚀梁、柱构件双线性恢复力模型特征点的计算方法,并通过弹塑性时程分析获得损伤模型中的其他参数数值。利用加权系数法合理地考虑锈蚀构件损伤向整体结构损伤迁移转化的多尺度效应,建立锈蚀钢框架整体地震损伤模型。结合该损伤模型的特点,定义了对应结构不同破坏等级的损

  19. Hemispheric specialization for linguistic processing of sung speech.

    Science.gov (United States)

    Yelle, Serena K; Grimshaw, Gina M

    2009-02-01

    The two hemispheres of the brain play complementary roles in song perception, with the left hemisphere specialized for processing the linguistic aspects of song and the right hemisphere specialized for the processing of melody. However, very little is known about how language and melody interact. The present study tested the hypothesis that right hemisphere linguistic processing would be facilitated by the presence of melody. In a dichotic listening paradigm, participants (8 men, 43 women) performed a linguistic task while listening to spoken or sung speech. Contrary to the hypothesis, left hemisphere specialization for linguistic processing was identical whether the sentences were spoken or sung.

  20. Survey results of corroding problems at biological treatment plants; Kartlaeggning av vittrings- och korrosionsskador paa biologiska behandlingsanlaeggningar

    Energy Technology Data Exchange (ETDEWEB)

    Boubitsas, Dimitrios; Aakesson, Urban (CBI, Boraas (Sweden)); Hellstroem, Hanna; Henriksson, Gunilla (SP, Boraas (Sweden))

    2010-03-15

    Problems regarding that leachate from food waste have been corroding vehicles and concrete slabs has been reported by Biogas- and composting plants. This is an issue that has been reported to Swedish Waste Management more often within the same pace as the volume of food waste gathering is increasing all around Sweden. The problem has also been addressed at inspections according to SPCR 120 Biogoedsel and SPCR 152 Kompost, where several plants have requested guidance/support/investigation to help solve their specific issue. Swedish Cement and Concrete Research Inst., has earlier completed some investigations which have been ordered by private plant owners/municipalities and the result from these investigations have often proved that the exposure classification has not been adjusted for its purpose. There is no clear definition regarding construction of concrete that is meant for usage in a receiving hall for food waste. It is likely that concrete for Biogas- and Composting plants are built to meet the demands of agricultural environments. The project will examine the magnitude of the problem regarding corrosion- and weathering damage on concrete slabs and cisterns at biological treatment plants. The project will also culminate to actual solutions for plants that are hit and to give advice to those in the danger zone and those who plan for new constructions. Through a survey handed to Biogas- and composting plants around the country, the width of the problem has been examined and what solutions plants have found and executed to solve this issue. A literature review has been implemented to find specific demands regarding concrete that is meant for a certain environment. Another four treatment plants have been examined. The studies that have been made are chemical analysis of leachate from food waste, analysis of drill cores and analysis of reinforcement corrosion. The results from this project show that concrete doesn't have enough resistance in these

  1. 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

  2. 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

  3. The calculating hemispheres: studies of a split-brain patient.

    Science.gov (United States)

    Funnell, Margaret G; Colvin, Mary K; Gazzaniga, Michael S

    2007-06-11

    The purpose of the study was to investigate simple calculation in the two cerebral hemispheres of a split-brain patient. In a series of four experiments, the left hemisphere was superior to the right in simple calculation, confirming the previously reported left hemisphere specialization for calculation. In two different recognition paradigms, right hemisphere performance was at chance for all arithmetic operations, with the exception of subtraction in a two-alternative forced choice paradigm (performance was at chance when the lure differed from the correct answer by a magnitude of 1 but above chance when the magnitude difference was 4). In a recall paradigm, the right hemisphere performed above chance for both addition and subtraction, but performed at chance levels for multiplication and division. The error patterns in that experiment suggested that for subtraction and addition, the right hemisphere does have some capacity for approximating the solution even when it is unable to generate the exact solution. Furthermore, right hemisphere accuracy in addition and subtraction was higher for problems with small operands than with large operands. An additional experiment assessed approximate and exact addition in the two hemispheres for problems with small and large operands. The left hemisphere was equally accurate in both tasks but the right hemisphere was more accurate in approximate addition than in exact addition. In exact addition, right hemisphere accuracy was higher for problems with small operands than large, but the opposite pattern was found for approximate addition.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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。

  18. Phenological changes in the southern hemisphere.

    Directory of Open Access Journals (Sweden)

    Lynda E Chambers

    Full Text Available Current evidence of phenological responses to recent climate change is substantially biased towards northern hemisphere temperate regions. Given regional differences in climate change, shifts in phenology will not be uniform across the globe, and conclusions drawn from temperate systems in the northern hemisphere might not be applicable to other regions on the planet. We conduct the largest meta-analysis to date of phenological drivers and trends among southern hemisphere species, assessing 1208 long-term datasets from 89 studies on 347 species. Data were mostly from Australasia (Australia and New Zealand, South America and the Antarctic/subantarctic, and focused primarily on plants and birds. This meta-analysis shows an advance in the timing of spring events (with a strong Australian data bias, although substantial differences in trends were apparent among taxonomic groups and regions. When only statistically significant trends were considered, 82% of terrestrial datasets and 42% of marine datasets demonstrated an advance in phenology. Temperature was most frequently identified as the primary driver of phenological changes; however, in many studies it was the only climate variable considered. When precipitation was examined, it often played a key role but, in contrast with temperature, the direction of phenological shifts in response to precipitation variation was difficult to predict a priori. We discuss how phenological information can inform the adaptive capacity of species, their resilience, and constraints on autonomous adaptation. We also highlight serious weaknesses in past and current data collection and analyses at large regional scales (with very few studies in the tropics or from Africa and dramatic taxonomic biases. If accurate predictions regarding the general effects of climate change on the biology of organisms are to be made, data collection policies focussing on targeting data-deficient regions and taxa need to be financially

  19. Detection of lightning in Saturn's Northern Hemisphere

    CERN Document Server

    Moghimi, Mohsen Hassanzadeh

    2012-01-01

    During Cassini flyby of Saturn at a radial distance 6.18R_s (Saturn Radius), a signal was detected from about 200 to 430 Hz that had the proper dispersion characteristics to be a whistler. The frequency-time dispersion of the whistler was found to be 81 Hz1/2s. Based on this dispersion constant, we determined, from a travel time computation, that the whistler must have originated from lightning in the northern hemisphere of Saturn. Using a simple centrifugal potential model consisting of water group ions, and hydrogen ions we also determine the fractional concentration and scale height that gave the best fit to the observed dispersion.

  20. Hemispherical sky simulator for daylighting model studies

    Energy Technology Data Exchange (ETDEWEB)

    Selkowitz, S.

    1981-07-01

    The design of a 24-foot-diameter hemispherical sky simulator recently completed at LBL is described. The goal was to produce a facility in which large models could be tested; which was suitable for research, teaching, and design; which could provide a uniform sky, an overcast sky, and several clear-sky luminance distributions, as well as accommodating an artificial sun. Initial operating experience with the facility is described, the sky simulator capabilities are reviewed, and its strengths and weaknesses relative to outdoor modeling tests are discussed.

  1. Hemispheric dominance and cell phone use.

    Science.gov (United States)

    Seidman, Michael D; Siegel, Bianca; Shah, Priyanka; Bowyer, Susan M

    2013-05-01

    A thorough understanding of why we hold a cell phone to a particular ear may be of importance when studying the impact of cell phone safety. To determine if there is an obvious association between sidedness of cell phone use and auditory hemispheric dominance (AHD) or language hemispheric dominance (LHD). It is known that 70% to 95% of the population are right-handed, and of these, 96% have left-brain LHD. We have observed that most people use their cell phones in their right ear. An Internet survey was e-mailed to individuals through surveymonkey.com. The survey used a modified Edinburgh Handedness Inventory protocol. Sample questions surveyed which hand was used to write with, whether the right or left ear was used for phone conversations, as well as whether a brain tumor was present. General community. An Internet survey was randomly e-mailed to 5000 individuals selected from an otology online group, patients undergoing Wada testing and functional magnetic resonance imaging, as well as persons on the university listserv, of which 717 surveys were completed. Determination of hemispheric dominance based on preferred ear for cell phone use. A total of 717 surveys were returned. Ninety percent of the respondents were right handed, and 9% were left handed. Sixty-eight percent of the right-handed people used the cell phone in their right ear, 25% in the left ear, and 7% had no preference. Seventy-two of the left-handed respondents used their left ear, 23% used their right ear, and 5% had no preference. Cell phone use averaged 540 minutes per month over the past 9 years. An association exists between hand dominance laterality of cell phone use (73%) and our ability to predict hemispheric dominance. Most right-handed people have left-brain LHD and use their cell phone in their right ear. Similarly, most left-handed people use their cell phone in their left ear. Our study suggests that AHD may differ from LHD owing to the difference in handedness and cell phone ear use

  2. Circular single domains in hemispherical Permalloy nanoclusters

    Energy Technology Data Exchange (ETDEWEB)

    Araujo, Clodoaldo I. L de, E-mail: dearaujo@ufv.br; Fonseca, Jakson M. [Departamento de Física, Universidade Federal de Viçosa, 36570-900 Viçosa-MG (Brazil); Sinnecker, João P. [Centro Brasileiro de Pesquisas Físicas, 22290-180 Rio de Janeiro-RJ (Brazil); Delatorre, Rafael G.; Garcia, Nicolas; Pasa, André A. [Departamento de Física, Universidade Federal de Santa Catarina, 88040-900 Florianópolis-SC (Brazil)

    2014-11-14

    We have studied ferromagnetic Permalloy clusters obtained by electrodeposition on n-type silicon. Magnetization measurements reveal hysteresis loops almost independent on temperature and very similar in shape to those obtained in nanodisks with diameter bigger than 150 nm. The spin configuration for the ground state, obtained by micromagnetic simulation, shows topological vortices with random chirality and polarization. This behavior in the small diameter clusters (∼80 nm) is attributed to the Dzyaloshinskii-Moriya interaction that arises in its hemispherical geometries. This magnetization behavior can be utilized to explain the magnetoresistance measured with magnetic field in plane and out of sample plane.

  3. Spatial disorientation in right-hemisphere infarction.

    Science.gov (United States)

    Meerwaldt, J D; van Harskamp, F

    1982-01-01

    Spatial orientation was tested with the rod orientation test. The subjects were 40 normal controls and 68 brain-damaged patients with cerebral infarcts. Patients in whom the lesion included the post-rolandic region of the right hemisphere performed worse than controls or patients with lesions at other sites. Patients with an exclusively postrolandic (usually occipital) lesion showed higher error rates than patients with a combined prerolandic and postrolandic lesion, but only for the visual part of the test. These patients were re-examined one year after the stroke. Most of them showed an incomplete recovery of spatial function. PMID:7119828

  4. The genus Platychara from the Western Hemisphere

    Science.gov (United States)

    Peck, R.E.; Forester, R.M.

    1979-01-01

    The systematics of four species belonging to the genus Platychara (Charophyta) from the Western Hemisphere is discussed. Three of the species, as defined herein, occur in Cretaceous and Paleocene rocks from Mexico through South America. The type species, P. compressa (Peck and Reker) Grambast, also of Cretaceous and Paleocene age, is herein restricted to deposits north of Mexico. These latter restrictions geographically separate P. compressa and P. perlata as presently defined but the relationship between these two species is still uncertain. A new species, P. grambastii, is proposed for specimens from Maestrichtian sediments in Jamaica. ?? 1979.

  5. 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.

  6. 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.

  7. 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.)

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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...

  13. 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.

  14. 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.

  15. 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...

  16. 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...

  17. 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

  18. 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

  19. 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...

  20. 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...

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Inter-hemispheric asymmetry of Pedersen conductance

    Science.gov (United States)

    Deng, Y.; Lu, Y.; Sheng, C.; Yue, X.

    2015-12-01

    Ionospheric conductance is very important to the magnetosphere-ionosphere coupling in the high latitude region, since it connects the polar cap potential with the currents. Meanwhile, the altitudinal distribution of Pederson conductance gives us a rough idea about the altitudinal distribution of Joule heating at high latitudes. Based on the Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC) satellites observations of electron density profiles from 2009-2014, Pedersen conductivity has been calculated. A climatologic study of the height-integrated Pedersen conductivities in both E (100-150 km) and F (150-600 km) regions and their ratio in different seasons, solar and geomagnetic conditions have been conducted. A significant inter-hemispheric asymmetry is identified in the seasonal variation. Meanwhile, the conductance in both regions and the conductance ratio show a strong dependence on F10.7 and Ap indices. This result will strongly help our understanding of the inter-hemispheric difference in the high-latitude electrodynamics.

  6. Flow past 2-D Hemispherical Rigid Canopies

    Science.gov (United States)

    Carnasciali, Maria-Isabel

    2013-11-01

    The flow past a 2-dimensional rigid hemispherical shape is investigated using PIV. Flow field measurements and images were generated with the use of a Thermoflow® apparatus. Results of this study are compared to prior work (APS DFD 2012 Session E9.00003) which employed CFD to investigate the flow in the near wake of hemispherical parachutes. The various sized gaps/open areas were positioned at distinct locations. The work presented here is part of a larger research project to investigate flow fields in deceleration devices and parachutes. Understanding the pitch-stability of parachutes is essential for accurate design and implementation of these deceleration devices but they present a difficult system to analyze. The flexibility of the parachute fabric results in large variations in the parachute geometry leading to complex fluid-structure interactions. Such flow, combined with flow through gaps and open areas, has been postulated to shed alternating vortices causing pitching/oscillations of the canopy. The results presented provide some insight into which geometric features affect vortex shedding and may enable the redesign of the baseline parachute to minimize instabilities.

  7. Novel hemispheric image formation: concepts and applications

    Science.gov (United States)

    Thibault, Simon; Konen, Pierre; Roulet, Patrice; Villegas, Mathieu

    2008-04-01

    Panoramic and hemispheric lens technologies represent new and exciting opportunities in both imaging and projection systems. Such lenses offer intriguing applications for the transportation/automotive industry, in the protection of civilian and military areas, business. In this paper we describe a new optical design technique that provides a greater degree of freedom in producing a variety of hemispheric spatial light distribution areas. This innovative optical design strategy, of generating and controlling image mapping, has been successful in producing high-resolution imaging and projection systems. This success has subsequently generated increased interest in the high-resolution camera/projector and the concept of absolute measurement with high-resolution wide-angle lenses. The new technique described in this paper uses optimization techniques to improve the performance of a customized wide-angle lens optical system for a specific application. By adding a custom angle-to-pixel ratio at the optical design stage, this customized optical system provides ideal image coverage while reducing and optimizing signal processing. This novel image formation technique requires the development of new algorithms in order to view the panoramic image on a display without any residual distortion.

  8. Hemisphere asymmetries for imitation of novel gestures.

    Science.gov (United States)

    Goldenberg, Georg; Strauss, Stefan

    2002-09-24

    Disorders of imitation are traditionally considered as a symptom of apraxia, but defective imitation of gestures can contrast with intact performance of gestures to verbal command and vice versa. It thus seems worthwhile to explore the neural basis of imitation of gestures independently of other manifestations of apraxia. To assess body part specificity of disturbances of imitation for meaningless gestures of fingers, hand, and foot. Imitation of meaningless gestures involving fingers (internal hand configuration), hand (external hand position), or foot was examined in 30 patients with left brain damage (LBD), 20 patients with right brain damage (RBD), and 20 normal control subjects. LBD affected imitation of hand and foot gestures more than imitation of finger gestures, whereas RBD had the strongest effect on finger gestures and affected foot gestures more than hand gestures. These results can be accounted for by the assumption that body part coding of gestures depends on left hemisphere function and that additional right hemisphere contributions are afforded when demands on perceptual discrimination rise.

  9. A Search for Hemispheric Asymmetry on Triton

    Science.gov (United States)

    McIntosh, C. M.; Storrs, A. D.

    2004-12-01

    We will present reconstructed images of Neptune's largest satellite Triton as part of an investigation of hemispheric asymmetry. The images we observed from the Hubble Space Telescope in July of 1997, using the Wide Field/Planetary Camera. The images were taken in several filters: F439W, F555W, and F791W. Image restoration was performed using the MISTRAL program (Mugnier, Fusco, and Conan 2003). We present the ratio between the filters to determine if there is any hemispheric color asymmetry at this time. The photometry of Triton appears normal in this data although Hicks and Buratti (2004) observe Triton to be anomalously red in August of 1997. References: Hicks, M.D., and Buratti, B.J. (2004): "The Spectral Variability of Triton from 1997-2000", Icarus 171 pp. 210-218 Mugnier, L.M., T. Fusco, and J.-M. Conan, 2003. "MISTRAL: a Myopic Edge-Preserving Image Restoration Method. Applicaton to Astronomical Adaptive Optics Corrected Long-Exposure Images." JOSA A (submitted)

  10. 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.

  11. 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.

  12. 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...

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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....

  19. 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.

  20. 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.

  1. 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...

  2. 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.

  3. 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...

  4. 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...

  5. 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.

  6. Effects of Linker Length and Transient Secondary Structure Elements in the Intrinsically Disordered Notch RAM Region on Notch Signaling.

    Science.gov (United States)

    Sherry, Kathryn P; Johnson, Scott E; Hatem, Christine L; Majumdar, Ananya; Barrick, Doug

    2015-11-01

    Formation of the bivalent interaction between the Notch intracellular domain (NICD) and the transcription factor CBF-1/RBP-j, Su(H), Lag-1 (CSL) is a key event in Notch signaling because it switches Notch-responsive genes from a repressed state to an activated state. Interaction of the intrinsically disordered RBP-j-associated molecule (RAM) region of NICD with CSL is thought to both disrupt binding of corepressor proteins to CSL and anchor NICD to CSL, promoting interaction of the ankyrin domain of NICD with CSL through an effective concentration mechanism. To quantify the role of disorder in the RAM linker region on the effective concentration enhancement of Notch transcriptional activation, we measured the effects of linker length variation on activation. The resulting activation profile has general features of a worm-like chain model for effective concentration. However, deviations from the model for short sequence deletions suggest that RAM contains sequence-specific structural elements that may be important for activation. Structural characterization of the RAM linker with sedimentation velocity analytical ultracentrifugation and NMR spectroscopy reveals that the linker is compact and contains three transient helices and two extended and dynamic regions. To test if these secondary structure elements are important for activation, we made sequence substitutions to change the secondary structure propensities of these elements and measured transcriptional activation of the resulting variants. Substitutions to two of these nonrandom elements (helix 2, extended region 1) have effects on activation, but these effects do not depend on the nature of the substituting residues. Thus, the primary sequences of these elements, but not their secondary structures, are influencing signaling.

  7. Activated NOTCH1 induces lung adenomas in mice and cooperates with MYC in the generation of lung adenocarcinoma

    OpenAIRE

    ALLEN, THADDEUS D.; Rodriguez, Elena M.; Jones, Kirk D.; Bishop, J. Michael

    2011-01-01

    NOTCH1 encodes the canonical member of the mammalian Notch receptor family. Activating lesions frequently affect NOTCH1 in T-cell acute lymphoblastic leukemia (T-ALL) and recently have been found in non-small cell lung cancer (NSCLC) as well. We explored the oncogenic potential of activated NOTCH1 in the lung by developing a transgenic mouse model in which activated NOTCH1 was overexpressed in the alveolar epithelium. The initial response to activated NOTCH1 was proliferation and the accumula...

  8. Notch effects on room temperature tensile and bend properties of Ni3Al and Ni3Al+B

    Science.gov (United States)

    Khadkikar, P. S.; Rigney, J. D.; Lewandowski, J. J.; Vedula, K.

    1989-01-01

    The notched mechanical properties of Ni3Al and Ni3Al+B prepared by powder metallurgy techniques have been determined in both tension and bending at room temperature. Tensile tests performed using double-notched specimens containing relatively blunt notches produced intergranular fracture in both Ni3Al and Ni3Al+B, with evidence of fracture initiating in an intergranular manner ahead of the blunt notch in both cases. Estimates of notched fracture toughness from bend tests and of local grain boundary fracture stress from the notched tensile tests suggest an increase in these values with boron addition.

  9. Influence of acid and alkaline corroded PVA fiber on strength of mortar%酸碱腐蚀PVA纤维对砂浆强度的影响

    Institute of Scientific and Technical Information of China (English)

    何锐; 李永鹏; 陈拴发; 邢明亮

    2013-01-01

    为研究聚乙烯醇(PVA)纤维的耐酸碱性及其对砂浆强度的影响,将相同质量的纤维分别浸泡在HCl和NaOH溶液中,测试其质量损失率随时间的变化,并采用扫描电子显微镜(SEM)观测其微观形貌的变化.同时,采用原状纤维和受腐蚀纤维分别制备纤维增强水泥砂浆,测试其抗压和抗拉强度,并采用SEM对试件断裂面微观形貌进行观测.结果表明,随着PVA纤维浸泡时间的延长,前3d质量损失率迅速增大,之后增长速率减小;经过酸碱腐蚀后,纤维表面微结构出现明显变化,在相同条件下经过HCl溶液处理过的纤维其表面破坏相对更严重;纤维的化学腐蚀对纤维砂浆的28 d抗压和抗拉强度几乎没有造成不良影响,说明尽管酸碱腐蚀作用能造成纤维的质量损失和表面层破损,但是其力学性能仍保持在较高水平,纤维表面层破损对提高其与基体的粘结有利.%The chemical stability of polyvinylalcohol (PVA) fibers and its influence on the strength of mortar were studied. Two samples of PVA fibers of the same amount were soaked in sodium hydroxide and hydrochloric acid solutions respectively, after which the mass loss ratio was measured. Scanning electron microscope (SEM) observation was performed to detect the surface morphologies of the fibers. The original and corroded fibers were both adopted to prepare cement mortar respectively and the strengths of the two kinds of cement mortar were measured. The fracture surface of the specimens was also detected by SEM. It was revealed that with the prolonging of immersion time, the mass loss ratio was increased sharply in the first 3 days and then the increment speed slowed down. There appears to be obvious changes for the micro morphology of the fibers. The damage to acid corroded fibers was worse than that to alkali corroded fibers at the same conditions. The strength of cement mortar prepared with corroded fibers at day 28 shows almost no

  10. Notch Activation Is Associated with Tetraploidy and Enhanced Chromosomal Instability in Meningiomas

    Directory of Open Access Journals (Sweden)

    Gilson S. Baia

    2008-06-01

    Full Text Available The Notch signaling cascade is deregulated in diverse cancer types. Specific Notch function in cancer is dependent on the cellular context, the particular homologs expressed, and cross-talk with other signaling pathways. We have previously shown that components of the Notch signaling pathway are deregulated in meningiomas. How-ever, the functional consequence of abnormal Notch signaling to meningiomas is unknown. Here, we report that exogenous expression of the Notch pathway effector, HES1, is associated with tetraploid cells in meningioma cell lines. Activated Notch1 and Notch2 receptors induced endogenous HES1 expression and were associated with tetraploidy in meningiomas. Tetraploid meningioma cells exhibited nuclear features of chromosomal instability and increased frequency of nuclear atypia, such as multipolar mitotic spindles and accumulation of cells with large nuclei. FACS-sorted tetraploid cells are viable but have higher rates of spontaneous apoptosis when compared with diploid cells. We have used spectral karyotyping to show that, in contrast to diploid cells, tetraploid cells develop a higher number of both numerical and structural chromosomal abnormalities. Our findings identify a novel function for the Notch signaling pathway in generating tetraploidy and contributing to chromosomal instability. We speculate that abnormal Notch signaling pathway is an initiating genetic mechanism for meningioma and potentially promotes tumor development.

  11. Characterization and analysis of surface notches on Ti-alloy plates fabricated by additive manufacturing techniques

    Science.gov (United States)

    Chan, Kwai S.

    2015-12-01

    Rectangular plates of Ti-6Al-4V with extra low interstitial (ELI) were fabricated by layer-by-layer deposition techniques that included electron beam melting (EBM) and laser beam melting (LBM). The surface conditions of these plates were characterized using x-ray micro-computed tomography. The depth and radius of surface notch-like features on the LBM and EBM plates were measured from sectional images of individual virtual slices of the rectangular plates. The stress concentration factors of individual surface notches were computed and analyzed statistically to determine the appropriate distributions for the notch depth, notch radius, and stress concentration factor. These results were correlated with the fatigue life of the Ti-6Al-4V ELI alloys from an earlier investigation. A surface notch analysis was performed to assess the debit in the fatigue strength due to the surface notches. The assessment revealed that the fatigue lives of the additively manufactured plates with rough surface topographies and notch-like features are dominated by the fatigue crack growth of large cracks for both the LBM and EBM materials. The fatigue strength reduction due to the surface notches can be as large as 60%-75%. It is concluded that for better fatigue performance, the surface notches on EBM and LBM materials need to be removed by machining and the surface roughness be improved to a surface finish of about 1 μm.

  12. Cell-type dependent modulation of Notch signaling by the amyloid precursor protein.

    Science.gov (United States)

    Oh, Sun Young; Chen, Ci-Di; Abraham, Carmela R

    2010-04-01

    The amyloid precursor protein is a ubiquitously expressed transmembrane protein that has been long implicated in the pathogenesis of Alzheimer's disease but its normal biological function has remained elusive despite extensive effort. We have previously reported the identification of Notch2 as an amyloid precursor protein interacting protein in E18 rat neurons. Here, we sought to reveal the physiologic consequences of this interaction. We report a functional relationship between amyloid precursor protein and Notch1, which does not affect Delta ligand binding. First, we observed interactions between the amyloid precursor protein and Notch in mouse embryonic stem cells lacking both presenilin 1 and presenilin 2, the active proteolytic components of the gamma-secretase complex, suggesting that these two transmembrane proteins can interact in the absence of presenilin. Next, we demonstrated that the amyloid precursor protein affects Notch signaling by using Notch-dependent luciferase assays in two cell lines, the human embryonic kidney 293 and the monkey kidney, COS7. We found that the amyloid precursor protein exerts opposing effects on Notch signaling in human embryonic kidney 293 vs. COS7 cells. Finally, we show that more Notch Intracellular Domain is found in the nucleus in the presence of exogenous amyloid precursor protein or its intracellular domain, suggesting the mechanism by which the amyloid precursor protein affects Notch signaling in certain cells. Our results provide evidence of potentially important communications between the amyloid precursor protein and Notch.

  13. Notch fatigue behavior: Metallic glass versus ultra-high strength steel

    Science.gov (United States)

    Wang, X. D.; Qu, R. T.; Wu, S. J.; Duan, Q. Q.; Liu, Z. Q.; Zhu, Z. W.; Zhang, H. F.; Zhang, Z. F.

    2016-01-01

    Studying the effect of notch on the fatigue behavior of structural materials is of significance for the reliability and safety designing of engineering structural components. In this work, we conducted notch fatigue experiments of two high-strength materials, i.e. a Ti32.8Zr30.2Ni5.3Cu9Be22.7 metallic glass (MG) and a 00Ni18Co15Mo8Ti ultra-high strength steel (CM400 UHSS), and compared their notch fatigue behavior. Experimental results showed that although both the strength and plasticity of the MG were much lower than those of the UHSS, the fatigue endurance limit of the notched MG approached to that of the notched UHSS, and the fatigue ratio of the notched MG was even higher. This interesting finding can be attributed to the unique shear banding mechanism of MG. It was found that during fatigue process abundant shear bands formed ahead of the notch root and in the vicinity of the crack in the notched MG, while limited plastic deformation was observed in the notched UHSS. The present results may improve the understanding on the fatigue mechanisms of high-strength materials and offer new strategies for structural design and engineering application of MG components with geometrical discontinuities. PMID:27752136

  14. Targeting Notch3 in Hepatocellular Carcinoma: Molecular Mechanisms and Therapeutic Perspectives.

    Science.gov (United States)

    Giovannini, Catia; Bolondi, Luigi; Gramantieri, Laura

    2016-12-28

    The Notch signaling pathway is a very conserved system that controls embryonic cell fate decisions and the maintenance of adult stem cells through cell to cell communication. Accumulating evidence support the relevance of Notch signaling in different human diseases and it is one of the most commonly activated signaling pathways in cancer. This review focuses mainly on the role of Notch3 signaling in hepatocellular carcinoma and its potential therapeutic applications against this malignancy. In this regard, the crosstalk between Notch and p53 may play an important role.

  15. Inhibition of Notch pathway prevents osteosarcoma growth by cell cycle regulation.

    Science.gov (United States)

    Tanaka, M; Setoguchi, T; Hirotsu, M; Gao, H; Sasaki, H; Matsunoshita, Y; Komiya, S

    2009-06-16

    The study shows constitutive activation of the Notch pathway in various types of malignancies. However, it remains unclear how the Notch pathway is involved in the pathogenesis of osteosarcoma. We investigated the expression of the Notch pathway molecules in osteosarcoma biopsy specimens and examined the effect of Notch pathway inhibition. Real-time PCR revealed overexpression of Notch2, Jagged1, HEY1, and HEY2. On the other hand, Notch1 and DLL1 were downregulated in biopsy specimens. Notch pathway inhibition using gamma-secretase inhibitor and CBF1 siRNA slowed the growth of osteosarcomas in vitro. In addition, gamma-secretase inhibitor-treated xenograft models exhibited significantly slower osteosarcoma growth. Cell cycle analysis revealed that gamma-secretase inhibitor promoted G1 arrest. Real-time PCR and western blot revealed that gamma-secretase inhibitor reduced the expression of accelerators of the cell cycle, including cyclin D1, cyclin E1, E2, and SKP2. On the other hand, p21(cip1) protein, a cell cycle suppressor, was upregulated by gamma-secretase inhibitor treatment. These findings suggest that inhibition of Notch pathway suppresses osteosarcoma growth by regulation of cell cycle regulator expression and that the inactivation of the Notch pathway may be a useful approach to the treatment of patients with osteosarcoma.

  16. 3D numerical analysis of crack propagation of heterogeneous notched rock under uniaxial tension

    Science.gov (United States)

    Wang, S. Y.; Sloan, S. W.; Sheng, D. C.; Tang, C. A.

    2016-05-01

    Macroscopic notches play an important role in evaluating the fracture process zone (FPZ) and the strengths of a heterogeneous rock mass. Crack initiation, propagation and coalescence for unnotched, single-notched and double-notched rock specimens are numerically simulated in a 3-D numerical model (RFPA3D). A feature of the code RFPA3D is that it can numerically simulate the evolution of cracks in three-dimensional space, as well as the heterogeneity of the rock mass. For the unnotched case, special attention is given to the complete stress-strain curve and the corresponding AE events for the failure process of rock specimen. By comparing with published experimental results, the simulation results from RFPA3D are found to be satisfactory. For the single-notched case, the effect of the length and the depth of the single notch and the thickness of the specimen on the failure mode and peak stress are evaluated. The 3D FPZ is very different from that in two dimensions. For the double-notched case, the effects of the separation distance and overlap distance of the double notches, as well as influence of the homogeneity index (m) are also investigated. As the overlap distance increases, the direction of the principal tensile stress at each notch-end changes from a perpendicular direction (tensile stress field) to a nearly parallel direction (compressive stress field), which affects the evolution of the cracks from the two notches.

  17. Spatiotemporal oscillations of Notch1, Dll1 and NICD are coordinated across the mouse PSM.

    Science.gov (United States)

    Bone, Robert A; Bailey, Charlotte S L; Wiedermann, Guy; Ferjentsik, Zoltan; Appleton, Paul L; Murray, Philip J; Maroto, Miguel; Dale, J Kim

    2014-12-01

    During somitogenesis, epithelial somites form from the pre-somitic mesoderm (PSM) in a periodic manner. This periodicity is regulated by a molecular oscillator, known as the 'segmentation clock', that is characterised by an oscillatory pattern of gene expression that sweeps the PSM in a caudal-rostral direction. Key components of the segmentation clock are intracellular components of the Notch, Wnt and FGF pathways, and it is widely accepted that intracellular negative-feedback loops regulate oscillatory gene expression. However, an open question in the field is how intracellular oscillations are coordinated, in the form of spatiotemporal waves of expression, across the PSM. In this study, we provide a potential mechanism for this process. We show at the mRNA level that the Notch1 receptor and Delta-like 1 (Dll1) ligand vary dynamically across the PSM of both chick and mouse. Remarkably, we also demonstrate similar dynamics at the protein level; hence, the pathway components that mediate intercellular coupling themselves exhibit oscillatory dynamics. Moreover, we quantify the dynamic expression patterns of Dll1 and Notch1, and show they are highly correlated with the expression patterns of two known clock components [Lfng mRNA and the activated form of the Notch receptor (cleaved Notch intracellular domain, NICD)]. Lastly, we show that Notch1 is a target of Notch signalling, whereas Dll1 is Wnt regulated. Regulation of Dll1 and Notch1 expression thus links the activity of Wnt and Notch, the two main signalling pathways driving the clock.

  18. Tumor-Suppressive Activity of Lunatic Fringe in Prostate through Differential Modulation of Notch Receptor Activation

    Directory of Open Access Journals (Sweden)

    Shubing Zhang

    2014-02-01

    Full Text Available Elevated Notch ligand and receptor expression has been associated with aggressive forms of prostate cancer, suggesting a role for Notch signaling in regulation of prostate tumor initiation and progression. Here, we report a critical role for Lunatic Fringe (Lfng, which encodes an O-fucosylpeptide 3-ß-N-acetylglucosaminyltransferase known to modify epidermal growth factor repeats of Notch receptor proteins, in regulation of prostate epithelial differentiation and proliferation, as well as in prostate tumor suppression. Deletion of Lfng in mice caused altered Notch activation in the prostate, associated with elevated accumulation of Notch1, Notch2, and Notch4 intracellular domains, decreased levels of the putative Notch3 intracellular fragment, as well as increased expression of Hes1, Hes5, and Hey2. Loss of Lfng resulted in expansion of the basal layer, increased proliferation of both luminal and basal cells, and ultimately, prostatic intraepithelial neoplasia. The Lfng-null prostate showed down-regulation of prostatic tumor suppressor gene NKX3.1 and increased androgen receptor expression. Interestingly, expression of LFNG and NKX3.1 were positively correlated in publically available human prostate cancer data sets. Knockdown of LFNG in DU-145 prostate cancer cells led to expansion of CD44+CD24− and CD49f+CD24− stem/progenitor-like cell population associated with enhanced prostatosphere-forming capacity. Taken together, these data revealed a tumor-suppressive role for Lfng in the prostate through differential regulation of Notch signaling.

  19. Regulation of angiogenesis via Notch signaling in breast cancer and cancer stem cells.

    Science.gov (United States)

    Zhou, Weiqiang; Wang, Guangdi; Guo, Shanchun

    2013-12-01

    Breast cancer angiogenesis is elicited and regulated by a number of factors including the Notch signaling. Notch receptors and ligands are expressed in breast cancer cells as well as in the stromal compartment and have been implicated in carcinogenesis. Signals exchanged between neighboring cells through the Notch pathway can amplify and consolidate molecular differences, which eventually dictate cell fates. Notch signaling and its crosstalk with many signaling pathways play an important role in breast cancer cell growth, migration, invasion, metastasis and angiogenesis, as well as cancer stem cell (CSC) self-renewal. Therefore, significant attention has been paid in recent years toward the development of clinically useful antagonists of Notch signaling. Better understanding of the structure, function and regulation of Notch intracellular signaling pathways, as well as its complex crosstalk with other oncogenic signals in breast cancer cells will be essential to ensure rational design and application of new combinatory therapeutic strategies. Novel opportunities have emerged from the discovery of Notch crosstalk with inflammatory and angiogenic cytokines and their links to CSCs. Combinatory treatments with drugs designed to prevent Notch oncogenic signal crosstalk may be advantageous over λ secretase inhibitors (GSIs) alone. In this review, we focus on the more recent advancements in our knowledge of aberrant Notch signaling contributing to breast cancer angiogenesis, as well as its crosstalk with other factors contributing to angiogenesis and CSCs.

  20. Notch signaling: targeting cancer stem cells and epithelial-to-mesenchymal transition.

    Science.gov (United States)

    Espinoza, Ingrid; Pochampally, Radhika; Xing, Fei; Watabe, Kounosuke; Miele, Lucio

    2013-09-06

    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.

  1. Notch Signaling Mediates Skeletal Muscle Atrophy in Cancer Cachexia Caused by Osteosarcoma

    Directory of Open Access Journals (Sweden)

    Xiaodong Mu

    2016-01-01

    Full Text Available Skeletal muscle atrophy in cancer cachexia is mediated by the interaction between muscle stem cells and various tumor factors. Although Notch signaling has been known as a key regulator of both cancer development and muscle stem cell activity, the potential involvement of Notch signaling in cancer cachexia and concomitant muscle atrophy has yet to be elucidated. The murine K7M2 osteosarcoma cell line was used to generate an orthotopic model of sarcoma-associated cachexia, and the role of Notch signaling was evaluated. Skeletal muscle atrophy was observed in the sarcoma-bearing mice, and Notch signaling was highly active in both tumor tissues and the atrophic skeletal muscles. Systemic inhibition of Notch signaling reduced muscle atrophy. In vitro coculture of osteosarcoma cells with muscle-derived stem cells (MDSCs isolated from normal mice resulted in decreased myogenic potential of MDSCs, while the application of Notch inhibitor was able to rescue this repressed myogenic potential. We further observed that Notch-activating factors reside in the exosomes of osteosarcoma cells, which activate Notch signaling in MDSCs and subsequently repress myogenesis. Our results revealed that signaling between tumor and muscle via the Notch pathway may play an important role in mediating the skeletal muscle atrophy seen in cancer cachexia.

  2. Targeting Notch3 in Hepatocellular Carcinoma: Molecular Mechanisms and Therapeutic Perspectives

    Directory of Open Access Journals (Sweden)

    Catia Giovannini

    2016-12-01

    Full Text Available The Notch signaling pathway is a very conserved system that controls embryonic cell fate decisions and the maintenance of adult stem cells through cell to cell communication. Accumulating evidence support the relevance of Notch signaling in different human diseases and it is one of the most commonly activated signaling pathways in cancer. This review focuses mainly on the role of Notch3 signaling in hepatocellular carcinoma and its potential therapeutic applications against this malignancy. In this regard, the crosstalk between Notch and p53 may play an important role.

  3. A Role for Notch Signalling in Breast Cancer and Endocrine Resistance

    Directory of Open Access Journals (Sweden)

    Ahmet Acar

    2016-01-01

    Full Text Available Over the past decade, there has been growing interest in the Notch signalling pathway within the breast cancer field. This interest stemmed initially from the observation that Notch signalling is aberrantly activated in breast cancer and its effects on various cellular processes including proliferation, apoptosis, and cancer stem cell activity. However more recently, elevated Notch signalling has been correlated with therapy resistance in oestrogen receptor-positive breast cancer. As a result, inhibiting Notch signalling with therapeutic agents is being explored as a promising treatment option for breast cancer patients.

  4. Deadly crosstalk: Notch signaling at the intersection of EMT and cancer stem cells.

    Science.gov (United States)

    Espinoza, Ingrid; Miele, Lucio

    2013-11-28

    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, in the biology of cancer stem cells, tumor angiogenesis and epithelial-to-mesenchymal transition (EMT) have been reported. This mini-review describes the role of Notch signaling deregulation in EMT and tumor aggressiveness. We describe how accumulated evidence suggests that Notch inhibition is an attractive strategy for the treatment of several cancers, at least in part because of its potential to reverse or prevent EMT.

  5. Prediction of multiaxial fatigue life for notched specimens of titanium alloy TC4

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Z. R.; Li, Z. X. [Southeast University, Nanjing (China); Hu, X. T.; Song, Y. D. [Nanjing University, Nanjing (China)

    2016-05-15

    Both the proportional and nonproportional multiaxial fatigue tests were conducted on two kinds of notched specimens of titanium alloy TC4. The multiaxial fatigue critical area of notched specimen is considered as the location experiencing the maximum damage. It is unsatisfactory to predict the multiaxial fatigue life with the local stress and strain in the fatigue critical area. The critical distance concepts are employed in the multiaxial life prediction method for notched specimens. The proposed method was checked by the test data of TC4 notched specimens. The prediction results are almost within a factor of three scatter band of the test results.

  6. Dual tumor suppressing and promoting function of Notch1 signaling in human prostate cancer.

    Science.gov (United States)

    Lefort, Karine; Ostano, Paola; Mello-Grand, Maurizia; Calpini, Valérie; Scatolini, Maria; Farsetti, Antonella; Dotto, G Paolo; Chiorino, Giovanna

    2016-07-26

    Adenocarcinomas of the prostate arise as multifocal heterogeneous lesions as the likely result of genetic and epigenetic alterations and deranged cell-cell communication. Notch signaling is an important form of intercellular communication with a role in growth/differentiation control and tumorigenesis. Contrasting reports exist in the literature on the role of this pathway in prostate cancer (PCa) development. We show here that i) compared to normal prostate tissue, Notch1 expression is significantly reduced in a substantial fraction of human PCas while it is unaffected or even increased in others; ii) acute Notch activation both inhibits and induces process networks associated with prostatic neoplasms; iii) down-modulation of Notch1 expression and activity in immortalized normal prostate epithelial cells increases their proliferation potential, while increased Notch1 activity in PCa cells suppresses growth and tumorigenicity through a Smad3-dependent mechanism involving p21WAF1/CIP1; iv) prostate cancer cells resistant to Notch growth inhibitory effects retain Notch1-induced upregulation of pro-oncogenic genes, like EPAS1 and CXCL6, also overexpressed in human PCas with high Notch1 levels. Taken together, these results reconcile conflicting data on the role of Notch1 in prostate cancer.

  7. Notch signaling is required for normal prostatic epithelial cell proliferation and differentiation.

    Science.gov (United States)

    Wang, Xi-De; Leow, Ching Ching; Zha, Jiping; Tang, Zhijun; Modrusan, Zora; Radtke, Freddy; Aguet, Michel; de Sauvage, Frederic J; Gao, Wei-Qiang

    2006-02-01

    Notch pathway is crucial for stem/progenitor cell maintenance, growth and differentiation in a variety of tissues. Using a transgenic cell ablation approach, we found in our previous study that cells expressing Notch1 are crucial for prostate early development and re-growth. Here, we further define the role of Notch signaling in regulating prostatic epithelial cell growth and differentiation using biochemical and genetic approaches in ex vivo or in vivo systems. Treatment of developing prostate grown in culture with inhibitors of gamma-secretase/presenilin, which is required for Notch cleavage and activation, caused a robust increase in proliferation of epithelial cells co-expressing cytokeratin 8 and 14, lack of luminal/basal layer segregation and dramatically reduced branching morphogenesis. Using conditional Notch1 gene deletion mouse models, we found that inactivation of Notch1 signaling resulted in profound prostatic alterations, including increased tufting, bridging and enhanced epithelial proliferation. Cells within these lesions co-expressed both luminal and basal cell markers, a feature of prostatic epithelial cells in predifferentiation developmental stages. Microarray analysis revealed that the gene expression in a number of genetic networks was altered following Notch1 gene deletion in prostate. Furthermore, expression of Notch1 and its effector Hey-1 gene in human prostate adenocarcinomas were found significantly down-regulated compared to normal control tissues. Taken together, these data suggest that Notch signaling is critical for normal cell proliferation and differentiation in the prostate, and deregulation of this pathway may facilitate prostatic tumorigenesis.

  8. Overexpression of protein O-fucosyltransferase 1 accelerates hepatocellular carcinoma progression via the Notch signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Lijie [Liver Surgery Department, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai (China); Dong, Pingping [Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai (China); Liu, Longzi; Gao, Qiang; Duan, Meng [Liver Surgery Department, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai (China); Zhang, Si; Chen, She [Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai (China); Xue, Ruyi, E-mail: xue.ruyi@zs-hospital.sh.cn [Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai (China); Wang, Xiaoying, E-mail: xiaoyingwang@fudan.edu.cn [Liver Surgery Department, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai (China)

    2016-04-29

    Aberrant activation of Notch signaling frequently occurs in liver cancer, and is associated with liver malignancies. However, the mechanisms regulating pathologic Notch activation in hepatocellular carcinoma (HCC) remain unclear. Protein O-fucosyltransferase 1 (Pofut1) catalyzes the addition of O-linked fucose to the epidermal growth factor-like repeats of Notch. In the present study, we detected the expression of Pofut1 in 8 HCC cell lines and 253 human HCC tissues. We reported that Pofut1 was overexpressed in HCC cell lines and clinical HCC tissues, and Pofut1 overexpression clinically correlated with the unfavorable survival and high disease recurrence in HCC. The in vitro assay demonstrated that Pofut1 overexpression accelerated the cell proliferation and migration in HCC cells. Furthermore, Pofut1 overexpression promoted the binding of Notch ligand Dll1 to Notch receptor, and hence activated Notch signaling pathway in HCC cells, indicating that Pofut1 overexpression could be a reason for the aberrant activation of Notch signaling in HCC. Taken together, our findings indicated that an aberrant activated Pofut1-Notch pathway was involved in HCC progression, and blockage of this pathway could be a promising strategy for the therapy of HCC. - Highlights: • Pofut1 overexpression in HCC was correlated with aggressive tumor behaviors. • Pofut1 overexpression in HCC was associated with poor prognosis. • Pofut1 promoted cell proliferation, migration and invasion in hepatoma cells. • Pofut1 activated Notch signaling pathway in hepatoma cells.

  9. hCLP46 regulates U937 cell proliferation via Notch signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Wenzhan; Du, Jie; Chu, Qiaoyun [College of Life Science, Graduate University of Chinese Academy of Sciences, Beijing 100049 (China); Wang, Youxin [School of Public Health and Family Medicine, Capital Medical University, Beijing 100069 (China); Liu, Lixin [College of Life Science, Graduate University of Chinese Academy of Sciences, Beijing 100049 (China); Song, Manshu [School of Public Health and Family Medicine, Capital Medical University, Beijing 100069 (China); Wang, Wei, E-mail: wei6014@yahoo.com [College of Life Science, Graduate University of Chinese Academy of Sciences, Beijing 100049 (China); School of Public Health and Family Medicine, Capital Medical University, Beijing 100069 (China)

    2011-04-29

    Highlights: {yields} Knock down of hCLP46 by RNAi impairs mammalian Notch signaling. {yields} hCLP46 affects neither cell surface Notch1 expression nor ligand-receptor binding. {yields} Knock down of hCLP46 inhibits U937 cell-growth by up-regulation of CDKN1B. -- Abstract: Human CAP10-like protein 46 kDa (hCLP46) is the homolog of Rumi, which is the first identified protein O-glucosyltransferase that modifies Notch receptor in Drosophila. Dysregulation of hCLP46 occurs in many hematologic diseases, but the role of hCLP46 remains unclear. Knockdown of hCLP46 by RNA interference resulted in decreased protein levels of endogenous Notch1, Notch intracellular domain (NICD) and Notch target gene Hes-1, suggesting the impairment of the Notch signaling. However, neither cell surface Notch expression nor ligand binding activities were affected. In addition, down-regulated expression of hCLP46 inhibited the proliferation of U937 cells, which was correlated with increased cyclin-dependent kinase inhibitor (CDKI) CDKN1B (p27) and decreased phosphorylation of retinoblastoma (RB) protein. We showed that lack of hCLP46 results in impaired ligand induced Notch activation in mammalian cell, and hCLP46 regulates the proliferation of U937 cell through CDKI-RB signaling pathway, which may be important for the pathogenesis of leukemia.

  10. Influence of Stacking Sequence and Notch Angle on the Charpy Impact Behavior of Hybrid Composites

    Science.gov (United States)

    Behnia, S.; Daghigh, V.; Nikbin, K.; Fereidoon, A.; Ghorbani, J.

    2016-09-01

    The low-velocity impact behavior of hybrid composite laminates was investigated. The epoxy matrix was reinforced with aramid, glass, basalt, and carbon fabrics using the hand lay-up technique. Different stacking sequences and notch angles were and notch angles considered and tested using a Charpy impact testing machine to study the hybridization and notch angle effects on the impact response of the hybrid composites. The energy absorption capability of specimens with different stacking sequences and notch angles is compared and discussed. It is shown that the hybridization can enhance the mechanical performance of composite materials.

  11. 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.

  12. Notch fatigue of ultrahigh molecular weight polyethylene (UHMWPE) used in total joint replacements.

    Science.gov (United States)

    Ansari, Farzana; Gludovatz, Bernd; Kozak, Adam; Ritchie, Robert O; Pruitt, Lisa A

    2016-07-01

    Ultrahigh molecular weight polyethylene (UHMWPE) has remained the primary polymer used in hip, knee and shoulder replacements for over 50 years. Recent case studies have demonstrated that catastrophic fatigue fracture of the polymer can severely limit device lifetime and are often associated with stress concentration (notches) integrated into the design. This study evaluates the influence of notch geometry on the fatigue of three formulations of UHMWPE that are in use today. A linear-elastic fracture mechanics approach is adopted to evaluate crack propagation as a function of notch root radius, heat treatment and Vitamin E additions. Specifically, a modified stress-intensity factor that accounts for notch geometry was utilized to model the crack driving force. The degree of notch plasticity for each material/notch combination was further evaluated using finite element methods. Experimental evaluation of crack speed as a function of stress intensity was conducted under cyclic tensile loading, taking crack length and notch plasticity into consideration. Results demonstrated that crack propagation in UHMWPE emanating from a notch was primarily affected by microstructural influences (cross-linking) rather than differences in notch geometry.

  13. Does Notch play a tumor suppressor role across diverse squamous cell carcinomas?

    Science.gov (United States)

    Zhang, Min; Biswas, Sangita; Qin, Xin; Gong, Wenrong; Deng, Wenbing; Yu, Hongjun

    2016-08-01

    The role of Notch pathway in tumorigenesis is highly variable. It can be tumor suppressive or pro-oncogenic, typically depending on the cellular context. Squamous cell carcinoma (SCC) is a cancer of the squamous cell, which can occur in diverse human tissues. SCCs are one of the most frequent human malignancies for which the pathologic mechanisms remain elusive. Recent genomic analysis of diverse SCCs identified marked levels of mutations in NOTCH1, implicating Notch signaling pathways in the pathogenesis of SCCs. In this review, evidences highlighting NOTCH's role in different types of SCCs are summarized. Moreover, based on accumulating structural information of the NOTCH receptor, the functional consequences of NOTCH1 gene mutations identified from diverse SCCs are analyzed, emphasizing loss of function of Notch in these cancers. Finally, we discuss the convergent view on an intriguing possibility that Notch may function as tumor suppressor in SCCs across different tissues. These mechanistic insights into Notch signaling pathways will help to guide the research of SCCs and development of therapeutic strategies for these cancers.

  14. Notch fatigue behavior: Metallic glass versus ultra-high strength steel

    Science.gov (United States)

    Wang, X. D.; Qu, R. T.; Wu, S. J.; Duan, Q. Q.; Liu, Z. Q.; Zhu, Z. W.; Zhang, H. F.; Zhang, Z. F.

    2016-10-01

    Studying the effect of notch on the fatigue behavior of structural materials is of significance for the reliability and safety designing of engineering structural components. In this work, we conducted notch fatigue experiments of two high-strength materials, i.e. a Ti32.8Zr30.2Ni5.3Cu9Be22.7 metallic glass (MG) and a 00Ni18Co15Mo8Ti ultra-high strength steel (CM400 UHSS), and compared their notch fatigue behavior. Experimental results showed that although both the strength and plasticity of the MG were much lower than those of the UHSS, the fatigue endurance limit of the notched MG approached to that of the notched UHSS, and the fatigue ratio of the notched MG was even higher. This interesting finding can be attributed to the unique shear banding mechanism of MG. It was found that during fatigue process abundant shear bands formed ahead of the notch root and in the vicinity of the crack in the notched MG, while limited plastic deformation was observed in the notched UHSS. The present results may improve the understanding on the fatigue mechanisms of high-strength materials and offer new strategies for structural design and engineering application of MG components with geometrical discontinuities.

  15. METHOD TO CALCULATE STRESS INTENSITY FACTOR OF V-NOTCH IN BI-MATERIALS

    Institute of Scientific and Technical Information of China (English)

    Youtang Li; Ming Song

    2008-01-01

    Based on Zak's stress function,the eigen-equation of stress singularity of bi-materials with a Ⅴ-notch was obtained.A new definition of stress intensity factor for a perpendicular inter facial Ⅴ-notch of bi-material was put forward.The effects of shear modulus and Poisson's ratio of the matrix material and attaching material on eigen-values were analyzed.A generalized ex pression for calculating KI of the perpendicular V-notch of bi-materials was obtained by means of stress extrapolation.Effects of notch depth,notch angle and Poisson's ratio of materials on the singular stress field near the tip of the Ⅴ-notch were analyzed systematically with numerical simulations.As an example,a finite plate with double edge notches under uniaxial uniform ten sion was calculated by the method presented and the influence of the notch angle and Poisson's ratio on the stress singularity near the tip of notch was obtained.

  16. Combining thermodynamic simulations, element and surface analytics to study U(VI) retention in corroded cement monoliths upon >20 years of leaching

    Science.gov (United States)

    Bube, C.; Metz, V.; Schild, D.; Rothe, J.; Dardenne, K.; Lagos, M.; Plaschke, M.; Kienzler, B.

    Retention or release of radionuclides in a deep geological repository for radioactive wastes strongly depends on the geochemical environment and on the interaction with near-field components, e.g. waste packages and backfill materials. Deep geological disposal in rock salt is one of the concepts considered for cemented low- and intermediate-level wastes. Long-term experiments were performed to observe the evolution of full-scale cemented waste simulates (doped with (NH4)2U2O7) upon reaction with relevant salt brines, e.g. MgCl2-rich and saturated NaCl solutions, and to examine the binding mechanisms of uranium. Throughout the experiments, concentrations of major solution components, uranium and pH values were monitored regularly and compared to thermodynamic equilibrium calculations, which indicate that close-to-equilibrium conditions have been achieved after 13-14 years duration of the leaching experiments. Two of the full-scale cemented waste simulates were recovered from the solutions after 17-18 years and studied by different analytical methods to characterize the solids, especially with respect to uranium incorporation. In drill core fragments of various lateral and horizontal positions of the corroded monoliths, U-rich aggregates were detected and analyzed by means of space-resolved techniques. Raman, μ-XANES and μ-XRD analyses of several aggregates demonstrate that they consist of an amorphous diuranate-type solid. Within error, calculated U solubilities controlled by Na-diuranate (Na2U2O7·H2O) are consistent with measured U concentrations in both, the NaCl and the MgCl2-system. Since uranophane occurs also in the corroded monoliths, it is proposed that a transition towards the thermodynamic equilibrium U(VI) phase is kinetically hindered.

  17. LEACHABILITY OF CHROME FROM MAGNESIA-CHROMITE REFRACTORY BRICKS CORRODED BY Cu/CuO- Na2O.2SiO2 SLAGS

    Directory of Open Access Journals (Sweden)

    David Medved

    2015-06-01

    Full Text Available The interactions of magnesia-chromite refractory brick with Cu-Na2O.2SiO2 and CuO-Na2O.2SiO2 melts are studied and the chemical durability of corrosion products in water is evaluated. The corrosion tests confirm intensive infiltration of the slag melts into the tested refractory bricks and formation of Cr(6+ compounds. The molten copper partially oxidizes during corrosion test by air and penetrates into bricks. Interactions among periclase (MgO and chromite (FeCr2O4 grains with the melt Na2O.2SiO2 and copper oxides makes possible to form several compounds (e.g. Cu2MgO3, CuCrO4, CaCrO4, Na2CrO4, MgCrO4. Just the marked yellow spots, which were observed on the corroded brick surface after 30 days of free storage, suggest hydration of the high-temperature corrosion products. The yellow color of spots points out to chromates as Na2CrO4 and MgCrO4, which are well soluble in water. The leaching of corroded bricks in water (batch leaching test of a ratio of S (solid : W (water = 0.1 taking up to 28 days confirmed the Cr, Na, Mg and Ca ions leach-out. The pH value of solution increased up to 9 during leaching mainly as a consequence of elevated Na+ ion concentration. The Cr ion concentration rises in the solution up to 1 mmol.l-1. The observed moderate decrease of Cr ion concentration in the solution with the length of leaching indicates super-saturation of the solution and precipitation of the products.

  18. Total hemispherical emissivity of Inconel 718

    Energy Technology Data Exchange (ETDEWEB)

    Keller, Benjamin P.; Nelson, Shawn E.; Walton, Kyle L.; Ghosh, Tushar K.; Tompson, Robert V.; Loyalka, Sudarshan K., E-mail: LoyalkaS@missouri.edu

    2015-06-15

    Highlights: • We have measured the total hemispherical emissivity for Inconel 718 from about 600–1250 K. • Oxidation in air at 1073 K resulted in an increase in emissivity. • Sandblasting of Inconel 718 was also observed to increase the emissivity. • Coating of graphite powder onto the ‘as-received’ Inconel 718 showed no increase in the emissivity. • Coating of graphite powder onto the 220 grit sandblasted Inconel 718 did show an increase in emissivity. - Abstract: Total hemispherical emissivity for Inconel 718 was measured in anticipation of its application in Very High Temperature Gas Reactors (VHTRs). A majority of current emissivity data for Inconel 718 is in the form of spectral measurements. The data presented here were obtained with an experimental apparatus based on the standard ASTM C835-06 for total hemispherical emittance. Measurements of Inconel 718 were made for four different surface types including: (i) ‘as-received’ from the manufacturer, (ii) oxidized in air and humidified helium, (iii) sandblasted with aluminum oxide powder, and (iv) with a thin coating of nuclear grade graphite powder (grade NGB-18). The emissivity for the ‘as-received’ sample ranged from 0.21 to 0.28 in the temperature interval from 760 K to 1275 K. Oxidation in air at 1073 K resulted in an increase in emissivity into the range from 0.2 at 650 K to 0.52 at 1200 K. There was no dependence on the oxidation times studied here. Oxidation with humidified helium at 1073 K produced less of an increase in emissivity than the oxidation in air but there was an increase up to the range from 0.2 at 600 K to 0.35 at 1200 K. Sandblasting of Inconel 718 was also observed to increase the emissivity up to the range from 0.43 at 780 K to 0.53 at 1270 K when 60 grit sized powder was used and up to the range from 0.45 at 683 K to 0.57 at 1267 K when 120 and 220 grit sized powders were used. Coating of graphite powder onto the ‘as-received’ Inconel 718 showed no increase

  19. The Research Progress of SiRNA Targeting Notch1 on Tumor Cells: A Mini Review of the State of the Art

    OpenAIRE

    Lanfen Huo; Shaoling Wu; Zhonghai Chi; Xindong Zhao

    2016-01-01

    Notch signaling is a highly conserved signaling pathway, playing an important role in a variety of cell differentiation, development and regulation. Notch signaling includes Notch1-4; Notch1 gene encodes Notch1 signaling that can shorten cell cycle, enhance cell proliferation, inhibit cell differentiation, and promote apoptosis. Mutation and overexpression of the Notch1 gene may induce tumorigenesis, which plays an important role in the development of tumors across a variety of signaling path...

  20. Shortwave Array Spectroradiometer–Hemispheric (SASHe) Instrument Handbook

    Energy Technology Data Exchange (ETDEWEB)

    Flynn, Connor J [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-04-01

    The Shortwave Array Spectroradiometer–Hemispheric (SASHe) provides measurements of direct solar, hemispheric diffuse, and total hemispheric shortwave irradiance over a continuous spectral range from approximately 300 nm to 1700 nm at a rate of about 30 seconds. The SASHe design connects an optical collector located outdoors to a pair of spectrometers and data collections systems located indoors within a climate-controlled building via an umbilical cable of fiber optic and electrical cables. The light collector uses a small Spectralon button as a hemispheric diffuser with a shadowband to distinguish signal from diffuse sky and direct sun.